<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.1 20151215//EN" "http://jats.nlm.nih.gov/publishing/1.1/JATS-journalpublishing1.dtd">
<article xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" dtd-version="1.1" specific-use="sps-1.9" article-type="rapid-communication" xml:lang="pt">
  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id specific-use="scielo-v3" pub-id-type="publisher-id">jtsBtVbfWGmr5fqbMfdfZyF</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2019000500649</article-id>
      <article-id pub-id-type="publisher-id">abc.20190086</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20190086</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Atualiza&#231;&#227;o</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Atualiza&#231;&#227;o das Diretrizes em Cardiogeriatria da Sociedade Brasileira de Cardiologia &#8211; 2019</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Feitosa</surname>
            <given-names>Gilson Soares</given-names>
            <suffix>Filho</suffix>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Peixoto</surname>
            <given-names>Jos&#233; Maria</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pinheiro</surname>
            <given-names>Jos&#233; Elias Soares</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">
            <sup>3</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Afiune</surname>
            <given-names>Abrah&#227;o</given-names>
            <suffix>Neto</suffix>
          </name>
          <xref ref-type="aff" rid="aff4">
            <sup>4</sup>
          </xref>
          <xref ref-type="aff" rid="aff5">
            <sup>5</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Albuquerque</surname>
            <given-names>Afonso Luiz Tavares de</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">
            <sup>6</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Cattani</surname>
            <given-names>&#193;lvaro C&#233;sar</given-names>
          </name>
          <xref ref-type="aff" rid="aff7">
            <sup>7</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nussbacher</surname>
            <given-names>Amit</given-names>
          </name>
          <xref ref-type="aff" rid="aff8">
            <sup>8</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Camarano</surname>
            <given-names>Ana Amelia</given-names>
          </name>
          <xref ref-type="aff" rid="aff9">
            <sup>9</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Sichinels</surname>
            <given-names>Angela Herm&#237;nia</given-names>
          </name>
          <xref ref-type="aff" rid="aff10">
            <sup>10</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Sousa</surname>
            <given-names>Antonio Carlos Sobral</given-names>
          </name>
          <xref ref-type="aff" rid="aff11">
            <sup>11</sup>
          </xref>
          <xref ref-type="aff" rid="aff12">
            <sup>12</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Alencar</surname>
            <given-names>Arist&#243;teles Comte de</given-names>
            <suffix>Filho</suffix>
          </name>
          <xref ref-type="aff" rid="aff13">
            <sup>13</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gravina</surname>
            <given-names>Claudia F.</given-names>
          </name>
          <xref ref-type="aff" rid="aff14">
            <sup>14</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Sobral</surname>
            <given-names>Dario Celestino</given-names>
            <suffix>Filho</suffix>
          </name>
          <xref ref-type="aff" rid="aff6">
            <sup>6</sup>
          </xref>
          <xref ref-type="aff" rid="aff15">
            <sup>15</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pitthan</surname>
            <given-names>Eduardo</given-names>
          </name>
          <xref ref-type="aff" rid="aff16">
            <sup>16</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Costa</surname>
            <given-names>Elisa Franco de Assis</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">
            <sup>3</sup>
          </xref>
          <xref ref-type="aff" rid="aff4">
            <sup>4</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Duarte</surname>
            <given-names>Elizabeth da Rosa</given-names>
          </name>
          <xref ref-type="aff" rid="aff17">
            <sup>17</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Freitas</surname>
            <given-names>Elizabete Viana de</given-names>
          </name>
          <xref ref-type="aff" rid="aff18">
            <sup>18</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Moriguchi</surname>
            <given-names>Emilio Hideyuki</given-names>
          </name>
          <xref ref-type="aff" rid="aff19">
            <sup>19</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mesquita</surname>
            <given-names>Evandro Tinoco</given-names>
          </name>
          <xref ref-type="aff" rid="aff20">
            <sup>20</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Fernandes</surname>
            <given-names>F&#225;bio</given-names>
          </name>
          <xref ref-type="aff" rid="aff21">
            <sup>21</sup>
          </xref>
          <xref ref-type="aff" rid="aff22">
            <sup>22</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Fuchs</surname>
            <given-names>Felipe Costa</given-names>
          </name>
          <xref ref-type="aff" rid="aff19">
            <sup>19</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Feitosa</surname>
            <given-names>Gilson Soares</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pierre</surname>
            <given-names>Humberto</given-names>
          </name>
          <xref ref-type="aff" rid="aff23">
            <sup>23</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pereira</surname>
            <given-names>Ilnei</given-names>
            <suffix>Filho</suffix>
          </name>
          <xref ref-type="aff" rid="aff24">
            <sup>24</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Helber</surname>
            <given-names>Izo</given-names>
          </name>
          <xref ref-type="aff" rid="aff23">
            <sup>23</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Borges</surname>
            <given-names>Jairo Lins</given-names>
          </name>
          <xref ref-type="aff" rid="aff23">
            <sup>23</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Garcia</surname>
            <given-names>J&#233;ssica Myrian de Amorim</given-names>
          </name>
          <xref ref-type="aff" rid="aff25">
            <sup>25</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Souza</surname>
            <given-names>Jos&#233; Antonio Gordillo de</given-names>
          </name>
          <xref ref-type="aff" rid="aff26">
            <sup>26</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Zanon</surname>
            <given-names>Jos&#233; Carlos da Costa</given-names>
          </name>
          <xref ref-type="aff" rid="aff27">
            <sup>27</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Alves</surname>
            <given-names>Josmar de Castro</given-names>
          </name>
          <xref ref-type="aff" rid="aff28">
            <sup>28</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mohallem</surname>
            <given-names>Kalil Lays</given-names>
          </name>
          <xref ref-type="aff" rid="aff29">
            <sup>29</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Chaves</surname>
            <given-names>Laura Mariana de Siqueira Mendon&#231;a</given-names>
          </name>
          <xref ref-type="aff" rid="aff25">
            <sup>25</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Moura</surname>
            <given-names>L&#237;dia Ana Zytynski</given-names>
          </name>
          <xref ref-type="aff" rid="aff30">
            <sup>30</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Silva</surname>
            <given-names>M&#225;rcia Cristina Am&#233;lia da</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">
            <sup>6</sup>
          </xref>
          <xref ref-type="aff" rid="aff15">
            <sup>15</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Toledo</surname>
            <given-names>Maria Alice de Vilhena</given-names>
          </name>
          <xref ref-type="aff" rid="aff31">
            <sup>31</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Assun&#231;&#227;o</surname>
            <given-names>Maria Elisa Lucena Sales de Melo</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">
            <sup>6</sup>
          </xref>
          <xref ref-type="aff" rid="aff15">
            <sup>15</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Wajngarten</surname>
            <given-names>Mauricio</given-names>
          </name>
          <xref ref-type="aff" rid="aff32">
            <sup>32</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gon&#231;alves</surname>
            <given-names>Mauro Jos&#233; Oliveira</given-names>
          </name>
          <xref ref-type="aff" rid="aff33">
            <sup>33</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lopes</surname>
            <given-names>Neuza Helena Moreira</given-names>
          </name>
          <xref ref-type="aff" rid="aff21">
            <sup>21</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rodrigues</surname>
            <given-names>Nezilour Lobato</given-names>
          </name>
          <xref ref-type="aff" rid="aff34">
            <sup>34</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Toscano</surname>
            <given-names>Paulo Roberto Pereira</given-names>
          </name>
          <xref ref-type="aff" rid="aff35">
            <sup>35</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rousseff</surname>
            <given-names>Pedro</given-names>
          </name>
          <xref ref-type="aff" rid="aff36">
            <sup>36</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Maia</surname>
            <given-names>Ricardo Antonio Rosado</given-names>
          </name>
          <xref ref-type="aff" rid="aff37">
            <sup>37</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Franken</surname>
            <given-names>Roberto Alexandre</given-names>
          </name>
          <xref ref-type="aff" rid="aff38">
            <sup>38</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Miranda</surname>
            <given-names>Roberto Dischinger</given-names>
          </name>
          <xref ref-type="aff" rid="aff23">
            <sup>23</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gamarski</surname>
            <given-names>Roberto</given-names>
          </name>
          <xref ref-type="aff" rid="aff39">
            <sup>39</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rosa</surname>
            <given-names>Ronaldo Fernandes</given-names>
          </name>
          <xref ref-type="aff" rid="aff38">
            <sup>38</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Santos</surname>
            <given-names>Silvio Carlos de Moraes</given-names>
          </name>
          <xref ref-type="aff" rid="aff40">
            <sup>40</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Galera</surname>
            <given-names>Siulmara Cristina</given-names>
          </name>
          <xref ref-type="aff" rid="aff41">
            <sup>41</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Grespan</surname>
            <given-names>Stela Maris da Silva</given-names>
          </name>
          <xref ref-type="aff" rid="aff23">
            <sup>23</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Silva</surname>
            <given-names>Teresa Cristina Rogerio da</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Esteves</surname>
            <given-names>William Antonio de Magalh&#227;es</given-names>
          </name>
          <xref ref-type="aff" rid="aff42">
            <sup>42</sup>
          </xref>
          <xref ref-type="aff" rid="aff43">
            <sup>43</sup>
          </xref>
          <xref ref-type="aff" rid="aff44">
            <sup>44</sup>
          </xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <aff id="aff1">
          <label>1</label>
          <institution content-type="orgname">Escola Bahiana de Medicina e Sa&#250;de P&#250;blica</institution>
          <addr-line>
            <named-content content-type="city">Salvador</named-content>
            <named-content content-type="state">BA</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Escola Bahiana de Medicina e Sa&#250;de P&#250;blica, Salvador, BA &#8211; Brasil</institution>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution content-type="orgname">Universidade Jos&#233; do Ros&#225;rio Vellano</institution>
          <addr-line>
            <named-content content-type="city">Belo Horizonte</named-content>
            <named-content content-type="state">MG</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade Jos&#233; do Ros&#225;rio Vellano (UNIFENAS), Belo Horizonte, MG &#8211; Brasil</institution>
        </aff>
        <aff id="aff3">
          <label>3</label>
          <institution content-type="orgname">Sociedade Brasileira de Geriatria e Gerontologia</institution>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Sociedade Brasileira de Geriatria e Gerontologia (SBGG), Rio de Janeiro, RJ &#8211; Brasil</institution>
        </aff>
        <aff id="aff4">
          <label>4</label>
          <institution content-type="orgname">Universidade Federal de Goi&#225;s</institution>
          <addr-line>
            <named-content content-type="city">Goi&#226;nia</named-content>
            <named-content content-type="state">GO</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade Federal de Goi&#225;s (UFG), Goi&#226;nia, GO &#8211; Brasil</institution>
        </aff>
        <aff id="aff5">
          <label>5</label>
          <institution content-type="orgname">UniEVANG&#201;LICA</institution>
          <addr-line>
            <named-content content-type="city">An&#225;polis</named-content>
            <named-content content-type="state">GO</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">UniEVANG&#201;LICA, An&#225;polis, GO &#8211; Brasil</institution>
        </aff>
        <aff id="aff6">
          <label>6</label>
          <institution content-type="orgname">Universidade de Pernambuco</institution>
          <addr-line>
            <named-content content-type="city">Recife</named-content>
            <named-content content-type="state">PE</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade de Pernambuco (UPE), Recife, PE &#8211; Brasil</institution>
        </aff>
        <aff id="aff7">
          <label>7</label>
          <institution content-type="orgname">Hospital S&#227;o Lucas</institution>
          <addr-line>
            <named-content content-type="city">Pato Branco</named-content>
            <named-content content-type="state">PR</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Hospital S&#227;o Lucas, Pato Branco, PR &#8211; Brasil</institution>
        </aff>
        <aff id="aff8">
          <label>8</label>
          <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade de S&#227;o Paulo (USP), S&#227;o Paulo, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff9">
          <label>9</label>
          <institution content-type="orgname">Instituto de Pesquisa Econ&#244;mica Aplicada</institution>
          <addr-line>
            <named-content content-type="city">Bras&#237;lia</named-content>
            <named-content content-type="state">DF</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Instituto de Pesquisa Econ&#244;mica Aplicada (IPEA), Bras&#237;lia, DF &#8211; Brasil</institution>
        </aff>
        <aff id="aff10">
          <label>10</label>
          <institution content-type="orgname">Hospital S&#227;o Juli&#227;o</institution>
          <addr-line>
            <named-content content-type="city">Campo Grande</named-content>
            <named-content content-type="state">MS</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Hospital S&#227;o Juli&#227;o, Campo Grande, MS &#8211; Brasil</institution>
        </aff>
        <aff id="aff11">
          <label>11</label>
          <institution content-type="orgname">Universidade Federal de Sergipe</institution>
          <addr-line>
            <named-content content-type="city">Aracaju</named-content>
            <named-content content-type="state">SE</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade Federal de Sergipe (UFS), Aracaju, SE &#8211; Brasil</institution>
        </aff>
        <aff id="aff12">
          <label>12</label>
          <institution content-type="orgname">Hospital S&#227;o Lucas</institution>
          <addr-line>
            <named-content content-type="city">Aracaju</named-content>
            <named-content content-type="state">SE</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Hospital S&#227;o Lucas, Aracaju, SE &#8211; Brasil</institution>
        </aff>
        <aff id="aff13">
          <label>13</label>
          <institution content-type="orgname">Universidade Federal do Amazonas</institution>
          <addr-line>
            <named-content content-type="city">Manaus</named-content>
            <named-content content-type="state">AM</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade Federal do Amazonas (UFAM), Manaus, AM &#8211; Brasil</institution>
        </aff>
        <aff id="aff14">
          <label>14</label>
          <institution content-type="orgname">Instituto Dante Pazzanese de Cardiologia</institution>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Instituto Dante Pazzanese de Cardiologia, S&#227;o Paulo, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff15">
          <label>15</label>
          <institution content-type="orgname">Pronto-Socorro Cardiol&#243;gico Universit&#225;rio de Pernambuco</institution>
          <addr-line>
            <named-content content-type="city">Recife</named-content>
            <named-content content-type="state">PE</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Pronto-Socorro Cardiol&#243;gico Universit&#225;rio de Pernambuco (PROCAPE), Recife, PE &#8211; Brasil</institution>
        </aff>
        <aff id="aff16">
          <label>16</label>
          <institution content-type="orgname">Universidade Federal da Fronteira Sul</institution>
          <addr-line>
            <named-content content-type="city">Chapec&#243;</named-content>
            <named-content content-type="state">SC</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade Federal da Fronteira Sul (UFFS), Chapec&#243;, SC &#8211; Brasil</institution>
        </aff>
        <aff id="aff17">
          <label>17</label>
          <institution content-type="orgname">Hospital Nossa Senhora da Concei&#231;&#227;o</institution>
          <addr-line>
            <named-content content-type="city">Tubar&#227;o</named-content>
            <named-content content-type="state">SC</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Hospital Nossa Senhora da Concei&#231;&#227;o (HNSC), Tubar&#227;o, SC &#8211; Brasil</institution>
        </aff>
        <aff id="aff18">
          <label>18</label>
          <institution content-type="orgname">Universidade do Estado do Rio de Janeiro</institution>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ &#8211; Brasil</institution>
        </aff>
        <aff id="aff19">
          <label>19</label>
          <institution content-type="orgname">Universidade Federal do Rio Grande do Sul</institution>
          <addr-line>
            <named-content content-type="city">Porto Alegre</named-content>
            <named-content content-type="state">RS</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade Federal do Rio Grande do Sul (UFRS), Porto Alegre, RS &#8211; Brasil</institution>
        </aff>
        <aff id="aff20">
          <label>20</label>
          <institution content-type="orgname">Universidade Federal Fluminense</institution>
          <addr-line>
            <named-content content-type="city">Niter&#243;i</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade Federal Fluminense (UFF), Niter&#243;i, RJ &#8211; Brasil</institution>
        </aff>
        <aff id="aff21">
          <label>21</label>
          <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
          <institution content-type="orgdiv1">Faculdade de Medicina</institution>
          <institution content-type="orgdiv2">Instituto do Cora&#231;&#227;o</institution>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Instituto do Cora&#231;&#227;o (Incor) da Faculdade de Medicina da Universidade de S&#227;o Paulo (FMUSP), S&#227;o Paulo, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff22">
          <label>22</label>
          <institution content-type="orgname">Sociedade Brasileira de Cardiologia</institution>
          <institution content-type="orgdiv1">Departamento de Insufici&#234;ncia Card&#237;aca</institution>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Departamento de Insufici&#234;ncia Card&#237;aca (DEIC) da Sociedade Brasileira de Cardiologia (SBC), Rio de Janeiro, RJ &#8211; Brasil</institution>
        </aff>
        <aff id="aff23">
          <label>23</label>
          <institution content-type="orgname">Universidade Federal de S&#227;o Paulo</institution>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade Federal de S&#227;o Paulo (UNIFESP), S&#227;o Paulo, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff24">
          <label>24</label>
          <institution content-type="orgname">Instituto de Cardiologia de Santa Catarina</institution>
          <addr-line>
            <named-content content-type="city">S&#227;o Jos&#233;</named-content>
            <named-content content-type="state">SC</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Instituto de Cardiologia de Santa Catarina (ICSC), S&#227;o Jos&#233;, SC &#8211; Brasil</institution>
        </aff>
        <aff id="aff25">
          <label>25</label>
          <institution content-type="orgname">Hospital Agamenon Magalh&#227;es</institution>
          <addr-line>
            <named-content content-type="city">Recife</named-content>
            <named-content content-type="state">PE</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Hospital Agamenon Magalh&#227;es, Recife, PE &#8211; Brasil</institution>
        </aff>
        <aff id="aff26">
          <label>26</label>
          <institution content-type="orgname">Sanofi</institution>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Sanofi, S&#227;o Paulo, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff27">
          <label>27</label>
          <institution content-type="orgname">Universidade Federal de Ouro Preto</institution>
          <addr-line>
            <named-content content-type="city">Ouro Preto</named-content>
            <named-content content-type="state">MG</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade Federal de Ouro Preto (UFOP), Ouro Preto, MG &#8211; Brasil</institution>
        </aff>
        <aff id="aff28">
          <label>28</label>
          <institution content-type="orgname">Procardio Cl&#237;nica Cardiol&#243;gica</institution>
          <addr-line>
            <named-content content-type="city">Natal</named-content>
            <named-content content-type="state">RN</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Procardio Cl&#237;nica Cardiol&#243;gica, Natal, RN &#8211; Brasil</institution>
        </aff>
        <aff id="aff29">
          <label>29</label>
          <institution content-type="orgname">Hospital Pr&#243;-Card&#237;aco</institution>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Hospital Pr&#243;-Card&#237;aco, Rio de Janeiro, RJ &#8211; Brasil</institution>
        </aff>
        <aff id="aff30">
          <label>30</label>
          <institution content-type="orgname">Pontif&#237;cia Universidade Universidade Cat&#243;lica do Paran&#225;</institution>
          <addr-line>
            <named-content content-type="city">Curitiba</named-content>
            <named-content content-type="state">PR</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Pontif&#237;cia Universidade Cat&#243;lica do Paran&#225; (PUC-PR), Curitiba, PR &#8211; Brasil</institution>
        </aff>
        <aff id="aff31">
          <label>31</label>
          <institution content-type="orgname">Universidade de Bras&#237;lia</institution>
          <addr-line>
            <named-content content-type="city">Bras&#237;lia</named-content>
            <named-content content-type="state">DF</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade de Bras&#237;lia (UnB), Bras&#237;lia, DF &#8211; Brasil</institution>
        </aff>
        <aff id="aff32">
          <label>32</label>
          <institution content-type="orgname">Hospital Israelita Albert Einstein</institution>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Hospital Israelita Albert Einstein, S&#227;o Paulo, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff33">
          <label>33</label>
          <institution content-type="orgname">Hospital S&#227;o Marcos</institution>
          <addr-line>
            <named-content content-type="city">Teresina</named-content>
            <named-content content-type="state">PI</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Hospital S&#227;o Marcos, Teresina, PI &#8211; Brasil</institution>
        </aff>
        <aff id="aff34">
          <label>34</label>
          <institution content-type="orgname">Universit&#225;rio Jo&#227;o de Barros Barreto</institution>
          <addr-line>
            <named-content content-type="city">Bel&#233;m</named-content>
            <named-content content-type="state">PA</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Hospital Universit&#225;rio Jo&#227;o de Barros Barreto, Bel&#233;m, PA &#8211; Brasil</institution>
        </aff>
        <aff id="aff35">
          <label>35</label>
          <institution content-type="orgname">Universidade do Estado do Par&#225;</institution>
          <addr-line>
            <named-content content-type="city">Bel&#233;m</named-content>
            <named-content content-type="state">PA</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade do Estado do Par&#225; (UEPA), Bel&#233;m, PA &#8211; Brasil</institution>
        </aff>
        <aff id="aff36">
          <label>36</label>
          <institution content-type="orgname">Hospital Madre Teresa</institution>
          <addr-line>
            <named-content content-type="city">Belo Horizontem</named-content>
            <named-content content-type="state">MG</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Hospital Madre Teresa, Belo Horizonte, MG &#8211; Brasil</institution>
        </aff>
        <aff id="aff37">
          <label>37</label>
          <institution content-type="orgname">Universidade Federal da Para&#237;ba</institution>
          <addr-line>
            <named-content content-type="city">Jo&#227;o Pessoa</named-content>
            <named-content content-type="state">PB</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade Federal da Para&#237;ba (UFPB), Jo&#227;o Pessoa, PB &#8211; Brasil</institution>
        </aff>
        <aff id="aff38">
          <label>38</label>
          <institution content-type="orgname">Faculdade de Ci&#234;ncias M&#233;dicas da Santa Casa de S&#227;o Paulo</institution>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Faculdade de Ci&#234;ncias M&#233;dicas da Santa Casa de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff39">
          <label>39</label>
          <institution content-type="orgname">Universidade Federal do Rio de Janeiro</institution>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ &#8211; Brasil</institution>
        </aff>
        <aff id="aff40">
          <label>40</label>
          <institution content-type="orgname">Instituto de An&#225;lises Cl&#237;nicas de Santos</institution>
          <addr-line>
            <named-content content-type="city">Santos</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Instituto de An&#225;lises Cl&#237;nicas de Santos (IACS), Santos, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff41">
          <label>41</label>
          <institution content-type="orgname">Universidade de Fortaleza</institution>
          <addr-line>
            <named-content content-type="city">Fortaleza</named-content>
            <named-content content-type="state">CE</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade de Fortaleza (UniFor), Fortaleza, CE &#8211; Brasil</institution>
        </aff>
        <aff id="aff42">
          <label>42</label>
          <institution content-type="orgname">Hospital Vera Cruz</institution>
          <addr-line>
            <named-content content-type="city">Belo Horizonte</named-content>
            <named-content content-type="state">MG</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Hospital Vera Cruz, Belo Horizonte, MG &#8211; Brasil</institution>
        </aff>
        <aff id="aff43">
          <label>43</label>
          <institution content-type="orgname">Universidade Federal de Minas Gerais</institution>
          <institution content-type="orgdiv1">Hospital das Cl&#237;nicas</institution>
          <addr-line>
            <named-content content-type="city">Belo Horizonte</named-content>
            <named-content content-type="state">MG</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Hospital das Cl&#237;nicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG &#8211; Brasil</institution>
        </aff>
        <aff id="aff44">
          <label>44</label>
          <institution content-type="orgname">Universidade de Ita&#250;na</institution>
          <addr-line>
            <named-content content-type="city">Ita&#250;na</named-content>
            <named-content content-type="state">MG</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade de Ita&#250;na, Ita&#250;na, MG &#8211; Brasil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><bold>Correspond&#234;ncia:</bold> Sociedade Brasileira de Cardiologia &#8211; Av. Marechal C&#226;mara, 360/330 &#8211; Centro &#8211; Rio de Janeiro &#8211; CEP: <postal-code>20020-907</postal-code>. E-mail: <email>sbc@cardiol.br</email></corresp>
      </author-notes>
      <pub-date publication-format="electronic" date-type="pub">
        <day>06</day>
        <month>06</month>
        <year>2019</year>
      </pub-date>
      <pub-date publication-format="electronic" date-type="collection">
        <month>05</month>
        <year>2019</year>
      </pub-date>
      <volume>112</volume>
      <issue>5</issue>
      <fpage>649</fpage>
      <lpage>705</lpage>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
        </license>
      </permissions>
      <counts>
        <fig-count count="4"/>
        <table-count count="88"/>
        <equation-count count="0"/>
        <ref-count count="332"/>
        <page-count count="57"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <table-wrap id="t1">
      <table frame="hsides" rules="groups">
        <colgroup width="12%">
          <col/>
          <col/>
          <col/>
          <col/>
          <col/>
          <col/>
          <col/>
          <col/>
        </colgroup>
        <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
          <tr>
            <th align="center" valign="top" colspan="8">Declara&#231;&#227;o de potencial conflito de interesses dos autores/colaboradores da Atualiza&#231;&#227;o das Diretrizes em Cardiogeriatria da Sociedade Brasileira de Cardiologia - 2019 Se nos &#250;ltimos 3 anos o autor/colaborador da Atualiza&#231;&#227;o:</th>
          </tr>
          <tr>
            <th align="left" valign="top">Nomes Integrantes da Atualiza&#231;&#227;o</th>
            <th align="left" valign="top">Participou de estudos cl&#237;nicos e/ou experimentais subvencionados pela ind&#250;stria farmac&#234;utica ou de equipamentos relacionados &#224; diretriz em quest&#227;o</th>
            <th align="left" valign="top">Foi palestrante em eventos ou atividades patrocinadas pela ind&#250;stria relacionados &#224; diretriz em quest&#227;o</th>
            <th align="left" valign="top">Foi (&#233;) membro do conselho consultivo ou diretivo da ind&#250;stria farmac&#234;utica ou de equipamentos</th>
            <th align="left" valign="top">Participou de comit&#234;s normativos de estudos cient&#237;ficos patrocinados pela ind&#250;stria</th>
            <th align="left" valign="top">Recebeu aux&#237;lio pessoal ou institucional da ind&#250;stria</th>
            <th align="left" valign="top">Elaborou textos cient&#237;ficos em peri&#243;dicos patrocinados pela ind&#250;stria</th>
            <th align="left" valign="top">Tem a&#231;&#245;es da ind&#250;stria</th>
          </tr>
        </thead>
        <tbody style="border-bottom: thin solid; border-color: #000000">
          <tr>
            <td align="left" valign="top">Abrah&#227;o Afiune Neto</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Afonso Luiz Tavares de Albuquerque</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">&#193;lvaro C&#233;sar Cattani</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Amit Nussbacher</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Ana Amelia Camarano</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Angela Herm&#237;nia Sichinels</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Antonio Carlos Sobral Sousa</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">Bayer, Ach&#233;, Pfizer</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Arist&#243;teles Comte de Alencar Filho</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Claudia F. Gravina</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Dario Celestino Sobral Filho</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">Libbs</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Eduardo Pitthan</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Elisa Franco de Assis Costa</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">Abbott, Nutrition</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">Abbott, Nutrition</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Elizabeth da Rosa Duarte</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">Torrent, Bayer, Ache, EMS</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Elizabete Viana de Freitas</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Emilio Hideyuki Moriguchi</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Evandro Tinoco Mesquita</td>
            <td align="center" valign="top">Novartis, Servier</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">F&#225;bio Fernandes</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">Pfizer</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Felipe Costa Fuchs</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Gilson Soares Feitosa</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Gilson Soares Feitosa-Filho</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Humberto Pierre</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Ilnei Pereira Filho</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Izo Helber</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Jairo Lins Borges</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">LIBBS Farmac&#234;utica</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">LIBBS Farmac&#234;utica</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">J&#233;ssica Myrian de Amorim Garcia</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">Pfizer</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Jos&#233; Antonio Gordillo de Souza</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">Sanofi</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Jos&#233; Carlos da Costa Zanon</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Jos&#233; Elias Soares Pinheiro</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Jos&#233; Maria Peixoto</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Josmar de Castro Alves</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Kalil Lays Mohallem</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Laura Mariana de Siqueira Mendon&#231;a Chaves</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">L&#237;dia Ana Zytynski Moura</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">M&#225;rcia Cristina Am&#233;lia da Silva</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Maria Alice de Vilhena Toledo</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Maria Elisa Lucena Sales de Melo Assun&#231;&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Mauricio Wajngarten</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Mauro Jos&#233; Oliveira Gon&#231;alves</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Neuza Helena Moreira Lopes</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Nezilour Lobato Rodrigues</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Paulo Roberto Pereira Toscano</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Pedro Rousseff</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Ricardo Antonio Rosado Maia</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Roberto Alexandre Franken</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Roberto Dischinger Miranda</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">Ach&#233;, Bayer, Biolab, Hypera, Sanofi</td>
            <td align="center" valign="top">Bayer, Boehringher, MSD</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">Biolab, Daiichi Sankyo, Pfizer</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Roberto Gamarski</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Ronaldo Fernandes Rosa</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Silvio Carlos de Moraes Santos</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Siulmara Cristina Galera</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Stela Maris da Silva Grespan</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">Teresa Cristina Rogerio da Silva</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
          <tr>
            <td align="left" valign="top">William Antonio de Magalh&#227;es Esteves</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
            <td align="center" valign="top">N&#227;o</td>
          </tr>
        </tbody>
      </table>
    </table-wrap>
    <sec>
      <title>1. Aspectos Gerais da Senilidade, Fatores de Risco e Preven&#231;&#227;o</title>
      <sec>
        <title>1.1. Aspectos Demogr&#225;ficos e Epidemiol&#243;gicos</title>
        <p>A partir da segunda metade do s&#233;culo XX, a sobreviv&#234;ncia democratizou-se em grande parte dos pa&#237;ses do mundo. Isto &#233;, mais pessoas est&#227;o alcan&#231;ando as idades mais avan&#231;adas. No Brasil, em 1980, de cada 100 crian&#231;as do sexo feminino nascidas vivas, 30 podiam esperar completar o anivers&#225;rio de 80 anos; em 2013, este n&#250;mero passou para 55. Consequentemente, a vida m&#233;dia da popula&#231;&#227;o brasileira aumentou quase 12 anos no per&#237;odo. Um dos fatores respons&#225;veis por esse movimento foi a queda da mortalidade nas idades avan&#231;adas, o que foi resultado do controle de doen&#231;as que antes eram letais. Mas muitas destas doen&#231;as que deixaram de ser letais n&#227;o s&#227;o cur&#225;veis. Como consequ&#234;ncia, cresce a popula&#231;&#227;o em idade mais avan&#231;ada, que tamb&#233;m envelhece e se torna mais heterog&#234;nea. Esta heterogeneidade se d&#225;, entre outros fatores, pela sua composi&#231;&#227;o por sexo, por idade e perfil epidemiol&#243;gico diferenciados. Por exemplo, dos aproximados 26 milh&#245;es de pessoas que tinham 60 anos ou mais, 56,4% eram mulheres e 13,8% tinham 80 anos ou mais de idade. Salienta-se ainda que n&#227;o s&#243; a continua&#231;&#227;o do processo de envelhecimento &#233; esperada, mas pode-se esperar, tamb&#233;m, o envelhecimento da pr&#243;pria popula&#231;&#227;o idosa. Ou seja, a popula&#231;&#227;o que mais cresce &#233; a de 80 anos ou mais, dada a redu&#231;&#227;o da mortalidade nestas idades.<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> (<xref ref-type="table" rid="t3">Tabela 1</xref>). &#201; sabido que o avan&#231;o da idade leva &#224; conviv&#234;ncia com doen&#231;as cr&#244;nicas, incapacitantes, que pode comprometer a autonomia das pessoas. Entre os idosos brasileiros, em 2013, apenas 22,3% declararam n&#227;o apresentar nenhuma doen&#231;a cr&#244;nica. Aproximadamente a metade, 48,6%, declarou ter uma ou duas doen&#231;as e 29,1%, tr&#234;s ou mais. As mulheres apresentam uma propor&#231;&#227;o mais elevada de contra&#237;rem alguma doen&#231;a do que os homens, 81,2% e 73,1%, respectivamente. A maior propor&#231;&#227;o de mulheres entre os idosos significa maior propor&#231;&#227;o de pessoas com morbidade cr&#244;nica<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> (<xref ref-type="table" rid="t2">Tabela 2</xref>). Dentre as doen&#231;as relatadas, predominaram as doen&#231;as cardiovasculares (DCV). Por exemplo, 62,0% dos homens e 67,4% das mulheres declararam ter hipertens&#227;o e 23,2% e 36,9% de homens e mulheres, respectivamente, afirmaram ter colesterol alto. Estas doen&#231;as constituem, tamb&#233;m, a principal causa de morte da popula&#231;&#227;o idosa; 34,2% e 35,2% dos &#243;bitos masculinos e femininos, respectivamente. Entre elas, destacam-se o infarto agudo do mioc&#225;rdio (IAM) e os acidentes vasculares encef&#225;licos (AVE)<xref ref-type="bibr" rid="B2"><sup>2</sup></xref> (Tabelas <xref ref-type="table" rid="t4">3</xref> e <xref ref-type="table" rid="t5">4</xref>).</p>
        <table-wrap id="t3">
          <label>Tabela 1</label>
          <caption>
            <title>Distribui&#231;&#227;o percentual da popula&#231;&#227;o idosa por sexo e idade<xref ref-type="bibr" rid="B1"><sup>1</sup></xref></title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="25%">
              <col/>
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr>
                <th align="center" valign="top"/>
                <th align="center" valign="top">Homens</th>
                <th align="center" valign="top">Mulheres</th>
                <th align="center" valign="top">Total</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top">60 a 69</td>
                <td align="center" valign="top">56,5</td>
                <td align="center" valign="top">56,3</td>
                <td align="center" valign="top">56,4</td>
              </tr>
              <tr>
                <td align="left" valign="top">70 a 79</td>
                <td align="center" valign="top">30,7</td>
                <td align="center" valign="top">29,4</td>
                <td align="center" valign="top">30</td>
              </tr>
              <tr>
                <td align="left" valign="top">80 a 89</td>
                <td align="center" valign="top">10,8</td>
                <td align="center" valign="top">12,2</td>
                <td align="center" valign="top">11,6</td>
              </tr>
              <tr>
                <td align="left" valign="top">90 ou mais</td>
                <td align="center" valign="top">2</td>
                <td align="center" valign="top">2,1</td>
                <td align="center" valign="top">2</td>
              </tr>
              <tr>
                <td align="left" valign="top">Total</td>
                <td align="center" valign="top">100</td>
                <td align="center" valign="top">100</td>
                <td align="center" valign="top">100</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN1">
              <p><italic>Brasil, 2013</italic>.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <table-wrap id="t2">
          <label>Tabela 2</label>
          <caption>
            <title>Propor&#231;&#227;o de idosos com doen&#231;as cr&#244;nicas por n&#250;mero de condi&#231;&#245;es patol&#243;gicas<xref ref-type="bibr" rid="B1"><sup>1</sup></xref></title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="25%">
              <col/>
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr>
                <th align="center" valign="top"/>
                <th align="center" valign="top">Homens</th>
                <th align="center" valign="top">Mulheres</th>
                <th align="center" valign="top">Total</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top">Nenhuma</td>
                <td align="center" valign="top">26,9</td>
                <td align="center" valign="top">18,8</td>
                <td align="center" valign="top">22,3</td>
              </tr>
              <tr>
                <td align="left" valign="top">1 a 2</td>
                <td align="center" valign="top">49,4</td>
                <td align="center" valign="top">48</td>
                <td align="center" valign="top">48,6</td>
              </tr>
              <tr>
                <td align="left" valign="top">3 ou mais</td>
                <td align="center" valign="top">23,7</td>
                <td align="center" valign="top">33,3</td>
                <td align="center" valign="top">29,1</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN2">
              <p><italic>Brasil, 2013</italic>.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <table-wrap id="t4">
          <label>Tabela 3</label>
          <caption>
            <title>Principais causas de morte dos idosos por sexo<xref ref-type="bibr" rid="B2"><sup>2</sup></xref></title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="33%">
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr>
                <th align="center" valign="top"/>
                <th align="center" valign="top">Homens</th>
                <th align="center" valign="top">Mulheres</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top">Doen&#231;as do aparelho circulat&#243;rio</td>
                <td align="center" valign="top">34,2</td>
                <td align="center" valign="top">35,2</td>
              </tr>
              <tr>
                <td align="left" valign="top">Neoplasias</td>
                <td align="center" valign="top">19,</td>
                <td align="center" valign="top">15,5</td>
              </tr>
              <tr>
                <td align="left" valign="top">Doen&#231;as do aparelho respirat&#243;rio</td>
                <td align="center" valign="top">14,3</td>
                <td align="center" valign="top">14,7</td>
              </tr>
              <tr>
                <td align="left" valign="top">Doen&#231;as end&#243;crinas nutricionais e metab&#243;licas</td>
                <td align="center" valign="top">6,5</td>
                <td align="center" valign="top">8,9</td>
              </tr>
              <tr>
                <td align="left" valign="top">Mal definidas</td>
                <td align="center" valign="top">6,2</td>
                <td align="center" valign="top">6,2</td>
              </tr>
              <tr>
                <td align="left" valign="top">Outras</td>
                <td align="center" valign="top">19,9</td>
                <td align="center" valign="top">19,5</td>
              </tr>
              <tr>
                <td align="left" valign="top">Total</td>
                <td align="center" valign="top">100</td>
                <td align="center" valign="top">100</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN3">
              <p><italic>Brasil, 2013</italic>.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <table-wrap id="t5">
          <label>Tabela 4</label>
          <caption>
            <title>Principais causas de morte por doen&#231;as do aparelho circulat&#243;rio por sexo<xref ref-type="bibr" rid="B2"><sup>2</sup></xref></title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="33%">
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr>
                <th align="center" valign="top"/>
                <th align="center" valign="top">Homens</th>
                <th align="center" valign="top">Mulheres</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top">Infarto agudo do mioc&#225;rdio</td>
                <td align="center" valign="top">26</td>
                <td align="center" valign="top">21,4</td>
              </tr>
              <tr>
                <td align="left" valign="top">Acidente vacular encef&#225;lico n&#227;o especificado como hemorr&#225;gico ou isqu&#234;mico</td>
                <td align="center" valign="top">13,7</td>
                <td align="center" valign="top">13,7</td>
              </tr>
              <tr>
                <td align="left" valign="top">Insufici&#234;ncia card&#237;aca</td>
                <td align="center" valign="top">8,2</td>
                <td align="center" valign="top">9,4</td>
              </tr>
              <tr>
                <td align="left" valign="top">Outras</td>
                <td align="center" valign="top">52</td>
                <td align="center" valign="top">55,5</td>
              </tr>
              <tr>
                <td align="left" valign="top">Total</td>
                <td align="center" valign="top">100</td>
                <td align="center" valign="top">100</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN4">
              <p><italic>Brasil, 2013</italic>.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Isso aponta para maior necessidade de preven&#231;&#227;o, em que mudan&#231;as no estilo de vida, controle do tabaco e do &#225;lcool, melhor dieta alimentar e exerc&#237;cios f&#237;sicos podem contribuir para a redu&#231;&#227;o das DCV. Em s&#237;ntese, pode-se dizer que a humanidade parece estar realizando o seu sonho, que &#233; o de viver muito, mas deve-se evitar a armadilha de Tithonus. Este &#233; um m&#237;tico troiano, a quem foi concedida vida eterna pelos deuses, mas ele esqueceu de pedir tamb&#233;m a eterna juventude. Eventualmente, transformou-se em uma cigarra. J&#225; Ulisses recusou o dom da imortalidade para continuar &#8220;dono do seu destino e capit&#227;o da sua alma&#8221; (Homero). Ou seja, viver muito e com autonomia deve ser o sonho da humanidade.</p>
      </sec>
      <sec>
        <title>1.2. Interpreta&#231;&#227;o da Fragilidade</title>
        <p>Fragilidade &#233; uma s&#237;ndrome biol&#243;gica caracterizada por diminui&#231;&#227;o da reserva homeost&#225;tica e da resist&#234;ncia a diversos estressores. Resulta de decl&#237;nios cumulativos em m&#250;ltiplos sistemas fisiol&#243;gicos e leva a aumento da vulnerabilidade e dos desfechos cl&#237;nicos desfavor&#225;veis, como quedas, decl&#237;nio funcional e da mobilidade, hospitaliza&#231;&#245;es, institucionaliza&#231;&#227;o e maior risco de morte.<xref ref-type="bibr" rid="B3"><sup>3</sup></xref> Esse estado de vulnerabilidade faz com que, diante de um insulto aparentemente pequeno (p. ex., infec&#231;&#227;o, introdu&#231;&#227;o de um novo medicamento ou mesmo uma pequena cirurgia), ocorra uma evidente e desproporcional mudan&#231;a no estado de sa&#250;de do paciente; essas mudan&#231;as podem ser exemplificadas como altera&#231;&#245;es de <italic>status</italic> de independente para dependente, de capaz de se locomover para imobilidade, de equil&#237;brio e marcha est&#225;veis para elevado risco de quedas, de l&#250;cido para delirante.<xref ref-type="bibr" rid="B4"><sup>4</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B5"><sup>5</sup></xref></p>
        <p>Existe uma superposi&#231;&#227;o, mas n&#227;o uma concord&#226;ncia na ocorr&#234;ncia de fragilidade, incapacidade e multimorbidade (coexist&#234;ncia de duas ou mais doen&#231;as cr&#244;nicas). Embora seja menos frequente, existem indiv&#237;duos fr&#225;geis sem incapacidade e sem a presen&#231;a de multimorbidade.<xref ref-type="bibr" rid="B4"><sup>4</sup></xref> A sarcopenia (diminui&#231;&#227;o da massa e da fun&#231;&#227;o muscular) &#233; um componente da s&#237;ndrome de fragilidade, sendo esta mais multifacetada e complexa que a sarcopenia isoladamente.<xref ref-type="bibr" rid="B5"><sup>5</sup></xref></p>
        <p>A apresenta&#231;&#227;o cl&#237;nica resulta n&#227;o s&#243; de uma &#250;nica doen&#231;a bem definida, mas do ac&#250;mulo de defici&#234;ncias em m&#250;ltiplos sistemas org&#226;nicos, e ocorre quando o efeito acumulado dessas defici&#234;ncias compromete a capacidade compensat&#243;ria do organismo. Uma revis&#227;o sistem&#225;tica demonstrou que a preval&#234;ncia de fragilidade entre idosos residentes na comunidade era de 10,7% (variando de 4,0% a 59,1%).<xref ref-type="bibr" rid="B6"><sup>6</sup></xref></p>
        <p>Nos portadores de doen&#231;a cardiovascular (DCV), a fragilidade confere um risco duas vezes maior de morte e este efeito persiste ap&#243;s ajuste para comorbidades e para a idade. In&#250;meros estudos demonstraram tamb&#233;m o aumento na preval&#234;ncia de fragilidade entre os portadores de DCV, como doen&#231;a arterial coronariana (DAC), insufici&#234;ncia card&#237;aca (IC), doen&#231;a valvar etc. Tamb&#233;m foi identificado maior risco de complica&#231;&#245;es e mortalidade entre os idosos fr&#225;geis submetidos a interven&#231;&#245;es cardiovasculares como cirurgias e angioplastias.<xref ref-type="bibr" rid="B7"><sup>7</sup></xref></p>
        <p>A fragilidade pode ser potencialmente prevenida ou tratada e diversos estudos demonstraram que interven&#231;&#245;es como exerc&#237;cios, suplementa&#231;&#227;o proteico-cal&#243;rica, suplementa&#231;&#227;o de vitamina D e redu&#231;&#227;o e otimiza&#231;&#227;o da polifarm&#225;cia podem diminuir o n&#237;vel de fragilidade, minimizando-se, assim, os desfechos adversos e os riscos das interven&#231;&#245;es.<xref ref-type="bibr" rid="B5"><sup>5</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B8"><sup>8</sup></xref></p>
        <p>A identifica&#231;&#227;o de idosos fr&#225;geis &#233; advogada para que se possa implementar as interven&#231;&#245;es multidimensionais, principalmente a reabilita&#231;&#227;o f&#237;sica e nutricional, reduzindo ou adiando os desfechos adversos bem como para prognosticar riscos. Conv&#233;m ressaltar que a identifica&#231;&#227;o da fragilidade n&#227;o deve ser vista como uma raz&#227;o para se negar ou suspender tratamentos, mas como um meio para se programarem interven&#231;&#245;es individualizadas e centradas no paciente.<xref ref-type="bibr" rid="B5"><sup>5</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B7"><sup>7</sup></xref></p>
        <p>Fried et al. (2001), em uma coorte de estudo longitudinal cardiovascular, identificaram as seguintes manifesta&#231;&#245;es da s&#237;ndrome: perda de peso n&#227;o intencional, fraqueza muscular, exaust&#227;o (fadiga), redu&#231;&#227;o da velocidade da marcha e diminui&#231;&#227;o do grau de atividade f&#237;sica. A partir delas, propuseram crit&#233;rios diagn&#243;sticos conhecidos como o &#8220;Fen&#243;tipo da Fragilidade de Fried et al.&#8221;,<xref ref-type="bibr" rid="B3"><sup>3</sup></xref> ou &#8220;Escala de Rastreio de Fragilidade do Cardiovascular Health Study&#8221;.<xref ref-type="bibr" rid="B3"><sup>3</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B5"><sup>5</sup></xref> A cr&#237;tica a esses crit&#233;rios s&#227;o que os referentes &#224; exaust&#227;o e &#224; redu&#231;&#227;o da atividade f&#237;sica n&#227;o s&#227;o objetivos e s&#227;o dif&#237;ceis de serem avaliados na pr&#225;tica di&#225;ria com idosos. Outros &#237;ndices e escalas para diagn&#243;stico foram propostos como o &#205;ndice de Fragilidade de Rockwood et al.,<xref ref-type="bibr" rid="B9"><sup>9</sup></xref> a Ge&#769;rontopo&#770;le Frailty Screening Tool,<xref ref-type="bibr" rid="B10"><sup>10</sup></xref> a escala FRAIL proposta por Van Kan e Morley,<xref ref-type="bibr" rid="B11"><sup>11</sup></xref> a Groningen Frailty Indicator,<xref ref-type="bibr" rid="B12"><sup>12</sup></xref> a Tilburg Frailty Indicator,<xref ref-type="bibr" rid="B13"><sup>13</sup></xref> o instrumento PRISMA-7,<xref ref-type="bibr" rid="B14"><sup>14</sup></xref> a escala VES-13<xref ref-type="bibr" rid="B15"><sup>15</sup></xref> e a Escala de Fragilidade de Edmonton.<xref ref-type="bibr" rid="B16"><sup>16</sup></xref> Os cinco &#250;ltimos instrumentos tiveram adapta&#231;&#227;o transcultural e/ou valida&#231;&#227;o no Brasil. Estudos t&#234;m demonstrado que o teste de velocidade de marcha de 5 metros &#233; uma ferramenta &#250;til na avalia&#231;&#227;o da fragilidade em idosos encaminhados para implante valvar a&#243;rtico percut&#226;neo.<xref ref-type="bibr" rid="B17"><sup>17</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B18"><sup>18</sup></xref> A incorpora&#231;&#227;o desta ferramenta ao escore STS (Society of Thoracic Surgeons) melhorou a capacidade preditora de eventos adversos. Para um dado escore STS o risco de mortalidade ou morbidade foi 2 a 3 vezes maior em pacientes com velocidade de marcha lenta.<xref ref-type="bibr" rid="B17"><sup>17</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B18"><sup>18</sup></xref> Independentemente do instrumento para rastreio e identifica&#231;&#227;o utilizado, a s&#237;ndrome de fragilidade deve ser pesquisada em todos idosos acima de 70 anos de idade e naqueles com DCV, mesmo que abaixo dessa faixa et&#225;ria, e medidas para a sua preven&#231;&#227;o e tratamento devem ser operacionalizadas.<xref ref-type="bibr" rid="B5"><sup>5</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B7"><sup>7</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B8"><sup>8</sup></xref></p>
      </sec>
      <sec>
        <title>1.3. Particularidades na Avalia&#231;&#227;o do Idoso</title>
        <p>O envelhecimento &#233; FR para a maioria das DCV, assim como de in&#250;meras comorbidades, tornando os idosos o grupo et&#225;rio de maior mais heterogeneidade e complexidade.<xref ref-type="bibr" rid="B19"><sup>19</sup></xref> De forma geral, o sistema de sa&#250;de &#233; mal preparado para assistir pacientes portadores de multimorbidades, visto que necessitam de uma individualiza&#231;&#227;o ainda maior e assist&#234;ncia por equipe multiprofissional trabalhando de forma integrada.<xref ref-type="bibr" rid="B20"><sup>20</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B21"><sup>21</sup></xref></p>
        <p>As interven&#231;&#245;es claramente ben&#233;ficas nos indiv&#237;duos adultos, de forma geral, tamb&#233;m o s&#227;o nos gerontes. Entretanto, as particularidades da avalia&#231;&#227;o do idoso s&#227;o fundamentais para o tratamento desses indiv&#237;duos. A avalia&#231;&#227;o dos pacientes idosos deve ser realizada por interm&#233;dio da Avalia&#231;&#227;o Geri&#225;trica Ampla (AGA).<xref ref-type="bibr" rid="B22"><sup>22</sup></xref> Esse &#233; um processo diagn&#243;stico multidimensional, geralmente interdisciplinar, para determinar as defici&#234;ncias, incapacidades e desvantagens do idoso e, ent&#227;o, planejar o seu cuidado e assist&#234;ncia a m&#233;dio e longo prazos. A AGA prioriza o estado funcional e a qualidade de vida, utilizando instrumentos de avalia&#231;&#227;o, facilitando a comunica&#231;&#227;o entre os membros da equipe interdisciplinar. Deve ser aplicada aos idosos fr&#225;geis e portadores de multimorbidades. A AGA &#233; tamb&#233;m &#233; um importante preditor de desfechos desfavor&#225;veis, ou seja, tem valor progn&#243;stico, para pacientes cir&#250;rgicos, oncol&#243;gicos e ortop&#233;dicos.<xref ref-type="bibr" rid="B22"><sup>22</sup></xref> A AGA &#233; fundamental no contexto da avalia&#231;&#227;o do idoso e contempla no m&#237;nimo quatro principais dimens&#245;es, que s&#227;o a capacidade funcional, as condi&#231;&#245;es m&#233;dicas, o funcionamento social e a sa&#250;de mental.<xref ref-type="bibr" rid="B22"><sup>22</sup></xref></p>
        <p>Idosos independentes, com expectativa de vida ativa longa, devem ser tratados de forma abrangente, combinando preven&#231;&#227;o e interven&#231;&#227;o. Por outro lado, os pr&#233;-fr&#225;geis e fr&#225;geis necessitam de maior aten&#231;&#227;o &#224;s necessidades e prioridades individuais, assim como ao risco/benef&#237;cio para decis&#227;o terap&#234;utica individualizada.<xref ref-type="bibr" rid="B19"><sup>19</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B20"><sup>20</sup></xref> As metas a serem alcan&#231;adas igualmente dependem do status funcional, n&#227;o se podendo contraindicar um tratamento, qualquer que seja ele, exclusivamente por causa da idade.</p>
        <p>Considerando a alta preval&#234;ncia de multimorbidades e a grande evolu&#231;&#227;o nas op&#231;&#245;es terap&#234;uticas, a polifarm&#225;cia torna-se muito frequente em idosos, trazendo desafios adicionais ao gerenciamento do caso.<xref ref-type="bibr" rid="B19"><sup>19</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B20"><sup>20</sup></xref> Entender as vantagens e desvantagens de cada tratamento &#233; fundamental para o tratamento adequado do idoso e s&#243; pode ser dimensionado por meio da AGA. Assim sendo, o conhecimento da AGA &#233; fundamental para avalia&#231;&#227;o e introdu&#231;&#227;o de um determinado tratamento no idoso.<xref ref-type="bibr" rid="B21"><sup>21</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B22"><sup>22</sup></xref></p>
      </sec>
      <sec>
        <title>1.4. Particularidades do Tratamento do Idoso</title>
        <p>No tratamento do idoso ganham prioridade o doente em rela&#231;&#227;o &#224; doen&#231;a e o controle da doen&#231;a em rela&#231;&#227;o &#224; cura. &#201; essencial conhecer a doen&#231;a, o doente e o tratamento. A doen&#231;a cardiovascular &#233; frequente e, mesmo quando tem poucas manifesta&#231;&#245;es, eleva riscos; o doente idoso apresenta comorbidades e alta vulnerabilidade biopsicossocial; os tratamentos s&#227;o mais suscet&#237;veis a efeitos indesejados. Assim, a avalia&#231;&#227;o em m&#250;ltiplos dom&#237;nios, cl&#237;nicos e psicossociais, &#233; fundamental. Devido &#224; frequente falta de evid&#234;ncias, as condutas devem ser individualizadas. As decis&#245;es devem ser compartilhadas e &#233; necess&#225;rio considerar a rela&#231;&#227;o risco/benef&#237;cio e a expectativa de vida. No idoso, a indica&#231;&#227;o de tratamentos exige mais cautela, as metas terap&#234;uticas s&#227;o menos precisas, por&#233;m soneg&#225;-las apenas devido &#224; idade implica omiss&#227;o.<xref ref-type="bibr" rid="B23"><sup>23</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B26"><sup>26</sup></xref></p>
        <p>As orienta&#231;&#245;es sobre mudan&#231;as no estilo de vida s&#227;o recomendadas, como nos mais jovens. Por&#233;m, tamb&#233;m podem causar efeitos indesejados, especialmente se mal-entendidas e mal-aplicadas. Mudar h&#225;bitos antigos merece aten&#231;&#227;o.</p>
        <p>Os tratamentos farmacol&#243;gicos devem: priorizar condi&#231;&#245;es e restringir o n&#250;mero de medicamentos, simplificar a posologia, avaliar e estimular a ades&#227;o insatisfat&#243;ria at&#233; na preven&#231;&#227;o secund&#225;ria ap&#243;s IAM,<xref ref-type="bibr" rid="B26"><sup>26</sup></xref> orientar sobre os problemas da automedica&#231;&#227;o, considerar as modifica&#231;&#245;es na farmacologia relacionadas &#224; idade que, de modo geral, recomendam redu&#231;&#227;o de doses, avaliar as poss&#237;veis intera&#231;&#245;es de f&#225;rmacos, pois &#233; comum a &#8220;polifarm&#225;cia&#8221;. Os Crit&#233;rios de Beers, informalmente conhecidos como a &#8220;Lista de Beers&#8221;, s&#227;o refer&#234;ncia sobre a seguran&#231;a da prescri&#231;&#227;o de medicamentos para os idosos. Foram criados em 1991 pelo geriatra Mark H. Beers e s&#227;o revisados periodicamente, sendo de 2015 a vers&#227;o mais recente.<xref ref-type="bibr" rid="B27"><sup>27</sup></xref></p>
        <p>Nos Estados Unidos mais de um ter&#231;o dos atendimentos de urg&#234;ncia devido a efeitos adversos de subst&#226;ncias ocorrem entre maiores de 65 anos e implicam hospitaliza&#231;&#227;o de mais de 40% dos casos, frequ&#234;ncia que vem se elevando com o tempo. Desses atendimentos, quase 60% foram relacionados ao uso de anticoagulantes, agentes antidiab&#233;ticos e analg&#233;sicos opioides e quase 2% foram relacionados a medicamentos de uso restrito, de acordo com os crit&#233;rios de Beers.<xref ref-type="bibr" rid="B28"><sup>28</sup></xref></p>
        <p>Recentemente, o Sistema de Notifica&#231;&#227;o de Eventos Adversos da <italic>Food and Drug Administration</italic> (FAERS; do ingl&#234;s, <italic>FDA &#8211; Adverse Event Reporting System</italic>) chamou a aten&#231;&#227;o para a avalia&#231;&#227;o da eventual necessidade de a&#231;&#227;o regulat&#243;ria para: os anticoagulantes apixabana, edoxabana, rivaroxabana e dabigatrana, devido a relatos de vasculite; a ivabradina, devido a potencial sinal de arritmias ventriculares; a midodrina, devido a relatos de intera&#231;&#227;o com inibidores de monoaminoxidase (IMAO) que poderia desencadear um AVE.<xref ref-type="bibr" rid="B29"><sup>29</sup></xref></p>
        <p>Os tratamentos intervencionistas devem ter indica&#231;&#227;o criteriosa, com a participa&#231;&#227;o de <italic>heart teams</italic> e realizados por equipes experientes e capacitadas, pois apresentam complica&#231;&#245;es mais frequentes e mais graves.</p>
        <p>Exemplo marcante para esse cen&#225;rio &#233; a necessidade de hospitaliza&#231;&#227;o ou interna&#231;&#227;o em casas de repouso de quatro em cada cinco idosos que recebem um cardiodesfibrilador implant&#225;vel para a dram&#225;tica preven&#231;&#227;o secund&#225;ria de morte s&#250;bita, apesar de sobreviverem pelo menos dois anos.<xref ref-type="bibr" rid="B30"><sup>30</sup></xref></p>
      </sec>
      <sec>
        <title>1.5. Diabetes Melito no Idoso</title>
        <p>A Pesquisa Nacional de Sa&#250;de realizada pelo Instituto Brasileiro de Geografia e Estat&#237;stica (IBGE, 2013) mostrou preval&#234;ncia de diabetes melito de 19,9% nos indiv&#237;duos na faixa et&#225;ria de 65 a 74 anos de idade.<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> No idoso diab&#233;tico h&#225; aumento da mortalidade e redu&#231;&#227;o da capacidade funcional com consequente aumento do risco de institucionaliza&#231;&#227;o.<xref ref-type="bibr" rid="B31"><sup>31</sup></xref> A presen&#231;a de multimorbidades e comorbidades associadas &#224; grande heterogeneidade deste grupo faz com que os idosos sejam frequentemente exclu&#237;dos dos estudos cl&#237;nicos randomizados, dificultando o manuseio da doen&#231;a nesta popula&#231;&#227;o.<xref ref-type="bibr" rid="B31"><sup>31</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B32"><sup>32</sup></xref></p>
        <p>Os crit&#233;rios diagn&#243;sticos para diabetes melito no idoso s&#227;o semelhantes aos da popula&#231;&#227;o mais jovem: (1) glicemia de jejum &#8805; 126 mg/dL; ou (2) glicemia ao acaso &#8805; 200 mg/dL associada a sintomas da doen&#231;a; ou (3) glicemia duas horas ap&#243;s sobrecarga de 75 g de glicose &#8805; 200 mg/dL; ou (4) hemoglobina glicosilada (HbA1C) &#8805; 6,5% (desde que o laborat&#243;rio seja padronizado). A <italic>American Diabetes Association</italic> (ADA) recomenda que indiv&#237;duos que apresentem excesso de peso como FR e todos os adultos com idade &#8805; 45 anos realizem rastreamento para diabetes a cada 1 a 3 anos com glicemia de jejum, dosagem de hemoglobina glicada ou teste de toler&#226;ncia oral &#224; glicose, pelo benef&#237;cio do diagn&#243;stico e do tratamento precoce na preven&#231;&#227;o de complica&#231;&#245;es.<xref ref-type="bibr" rid="B31"><sup>31</sup></xref></p>
        <p>Os indiv&#237;duos idosos com diabetes t&#234;m risco aumentado para desenvolvimento das s&#237;ndromes geri&#225;tricas, tais como polifarm&#225;cia, d&#233;ficit cognitivo, incontin&#234;ncia urin&#225;ria, quedas e dor cr&#244;nica; os indiv&#237;duos com estas s&#237;ndromes que desenvolvem diabetes t&#234;m seu quadro agravado. Desta forma, &#233; fundamental, al&#233;m do rastreamento para complica&#231;&#245;es, uma avalia&#231;&#227;o multidimensional do indiv&#237;duo idoso diab&#233;tico. A realiza&#231;&#227;o da AGA com avalia&#231;&#245;es mental, funcional, nutricional e social destes indiv&#237;duos torna-se imperativa para definirmos os alvos a serem atingidos em cada paciente.<xref ref-type="bibr" rid="B32"><sup>32</sup></xref> O objetivo deve ser definido entre duas op&#231;&#245;es: controle glic&#234;mico rigoroso e menor progress&#227;o das complica&#231;&#245;es cr&#244;nicas; ou controle glic&#234;mico n&#227;o rigoroso, apenas evitar sintomas de hiperglicemia e complica&#231;&#245;es agudas.</p>
        <p>O <italic>United Kingdom Prospective Diabetes Study</italic> (UKPDS), apesar de excluir idosos, mostrou os benef&#237;cios do controle glic&#234;mico rigoroso nos indiv&#237;duos ao envelhecerem, acompanhados posteriormente.<xref ref-type="bibr" rid="B33"><sup>33</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B34"><sup>34</sup></xref> S&#227;o tr&#234;s os principais estudos cl&#237;nicos randomizados com participa&#231;&#227;o de idosos e controle glic&#234;mico rigoroso: no <italic>Action to Control Cardiovascular Risk in Diabetes</italic> (ACCORD), o estudo foi interrompido devido &#224; mortalidade no grupo mais jovem; por&#233;m, hipoglicemia e outros efeitos adversos do tratamento foram mais comuns nos idosos;<xref ref-type="bibr" rid="B35"><sup>35</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B36"><sup>36</sup></xref> no estudo <italic>Action in Diabetes and Vascular Disease: Preteraax and Diamicron MR Controlled Evaluation</italic> (ADVANCE) o risco de hipoglicemia e hospitaliza&#231;&#227;o aumentou significativamente;<xref ref-type="bibr" rid="B37"><sup>37</sup></xref> e no estudo <italic>Veterans Affairs Diabetes Trial</italic> (VADT) n&#227;o houve benef&#237;cios, com exce&#231;&#227;o da diminui&#231;&#227;o da progress&#227;o da microalbuminuria.<xref ref-type="bibr" rid="B38"><sup>38</sup></xref> Dois estudos retrospectivos ( <italic>U. K. General Practice Research Database</italic>, 2009<xref ref-type="bibr" rid="B39"><sup>39</sup></xref> e <italic>The Diabetes and Aging Study</italic>, 2011) mostraram uma curva em &#8220;U&#8221; relacionando mortalidade e n&#237;veis glic&#234;micos.<xref ref-type="bibr" rid="B40"><sup>40</sup></xref> Desta forma, &#233; imperativa a individualiza&#231;&#227;o do tratamento nos pacientes idosos de acordo com seu perfil cl&#237;nico, funcional e expectativa de vida, conforme demonstrado na <xref ref-type="table" rid="t6">Tabela 5</xref>, com as metas tamb&#233;m para hipertens&#227;o arterial e dislipidemia nos idosos diab&#233;ticos.</p>
        <table-wrap id="t6">
          <label>Tabela 5</label>
          <caption>
            <title>Metas de tratamento para glicemia, press&#227;o arterial e dislipidemia em idosos diab&#233;ticos</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="14%">
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr>
                <th align="left" valign="middle">Caracter&#237;sticas do paciente/estado de sa&#250;de</th>
                <th align="center" valign="middle">Justificativa</th>
                <th align="center" valign="top">Meta razo&#225;vel de HbA1C</th>
                <th align="center" valign="top">Glicemia em jejum ou pr&#233;-prandial (mg/dL)</th>
                <th align="center" valign="top">Glicemia <italic>bedtime</italic> (mg/dL)</th>
                <th align="center" valign="middle">Press&#227;o arterial (mmHg)</th>
                <th align="center" valign="middle">Lip&#237;dios</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top">Saud&#225;vel (poucas doen&#231;as cr&#244;nicas coexistindo, cogni&#231;&#227;o e estado funcional intactos)</td>
                <td align="center" valign="top">Longa expectativa de vida</td>
                <td align="center" valign="middle">&lt; 7,5%</td>
                <td align="center" valign="middle">90-130</td>
                <td align="center" valign="middle">90-150</td>
                <td align="center" valign="top">&lt; 140/90</td>
                <td align="center" valign="top">Estatina, se n&#227;o houver contraindica&#231;&#227;o ou intoler&#226;ncia</td>
              </tr>
              <tr>
                <td align="left" valign="top">Complexo/intermedi&#225;rio (m&#250;ltiplas doen&#231;as cr&#244;nicas coexistindo ou AIVD prejudicadas ou d&#233;ficit cognitivo leve a moderado)</td>
                <td align="center" valign="top">Intermedi&#225;ria expectativa de vida, alta carga de tratamento, vulnerabilidade a hipoglicemia, risco de quedas</td>
                <td align="center" valign="middle">&lt; 8,0%</td>
                <td align="center" valign="middle">90-150</td>
                <td align="center" valign="middle">100-180</td>
                <td align="center" valign="top">&lt; 140/90</td>
                <td align="center" valign="top">Estatina, se n&#227;o houver contraindica&#231;&#227;o ou intoler&#226;ncia</td>
              </tr>
              <tr>
                <td align="left" valign="top">Muito complexo/sa&#250;de piorada (cuidados a longo tempo ou est&#225;gio final de doen&#231;as cr&#244;nicas ou moderado a grave d&#233;ficit cognitivo ou 2+ depend&#234;ncia nas ABVD)</td>
                <td align="center" valign="top">Limitada expectativa de vida torna o benef&#237;cio incerto</td>
                <td align="center" valign="middle">&lt; 8,5%</td>
                <td align="center" valign="middle">100-180</td>
                <td align="center" valign="middle">110-200</td>
                <td align="center" valign="top">&lt; 150/90</td>
                <td align="center" valign="top">Considerar a probabilidade do benef&#237;cio com estatina (preven&#231;&#227;o secund&#225;ria mais do que prim&#225;ria)</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN5">
              <p><italic>ABVD: atividades b&#225;sicas de vida di&#225;ria; AIVD: atividades instrumentais de vida di&#225;ria; HbA1C: hemoglobina glicosilada. Fonte: American Diabetes Association. Older adults. Diabetes Care. 2017; 40 (suppl.1):S99-S104</italic>.<xref ref-type="bibr" rid="B32"><sup>32</sup></xref></p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>1.6. Tabagismo</title>
        <p>A influ&#234;ncia do tabagismo no idoso ocorre pelas altera&#231;&#245;es anat&#244;micas e fisiol&#243;gicas de um processo acumulativo que leva a disfun&#231;&#227;o endotelial, aumento da adesividade plaquet&#225;ria, diminui&#231;&#227;o do colesterol de lipoprote&#237;nas de alta densidade (HDL-c) e aumento do colesterol de lipoprote&#237;nas de baixa densidade (LDL-c), entre outras altera&#231;&#245;es.<xref ref-type="bibr" rid="B41"><sup>41</sup></xref> O uso de tabaco na popula&#231;&#227;o idosa &#233; comum e &#233; causa importante de morbidade e mortalidade, incluindo DCV, doen&#231;a vascular perif&#233;rica, doen&#231;a cerebrovascular, c&#226;ncer e doen&#231;a pulmonar obstrutiva. No entanto, a cessa&#231;&#227;o do tabagismo tem benef&#237;cios mesmo em pacientes idosos no que diz respeito &#224; preven&#231;&#227;o dessas doen&#231;as ou, pelo menos, retardando o decl&#237;nio da fun&#231;&#227;o pulmonar.<xref ref-type="bibr" rid="B42"><sup>42</sup></xref> O Systolic Hypertension in the Elderly Program Study<xref ref-type="bibr" rid="B43"><sup>43</sup></xref> observou pacientes com idade m&#233;dia de 72 anos e constatou aumento significativo de IAM, morte s&#250;bita e AVE em fumantes em compara&#231;&#227;o a n&#227;o fumantes. A exposi&#231;&#227;o a longos per&#237;odos de tabagismo passivo aumenta o risco de desenvolver DAC. Kawachi et al. (1997)<xref ref-type="bibr" rid="B44"><sup>44</sup></xref> seguiram por 10 anos 32 mil mulheres n&#227;o tabagistas, com idade entre 36 e 71 anos, e constataram que o risco relativo de desenvolver doen&#231;a coronariana aumentou para as mulheres expostas ao fumo. A exposi&#231;&#227;o ocasional ao cigarro aumentou seu risco relativo para 1,58, enquanto a exposi&#231;&#227;o regular aumentou o risco relativo para 1,91.<xref ref-type="bibr" rid="B45"><sup>45</sup></xref> O tabagismo constitui-se em fator de risco (FR) para a dem&#234;ncia e seu abandono pode reduzir a carga de dem&#234;ncia. A exposi&#231;&#227;o passiva ao fumo tamb&#233;m pode aumentar o risco de dem&#234;ncia.<xref ref-type="bibr" rid="B46"><sup>46</sup></xref> Estudos mostram que os fumantes idosos apresentam menor inten&#231;&#227;o em abandonar o cigarro se comparados aos jovens; mas t&#234;m, em contrapartida, maior probabilidade de sucesso quando tentam parar de fumar.<xref ref-type="bibr" rid="B47"><sup>47</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B48"><sup>48</sup></xref> Com frequ&#234;ncia, o sucesso na interrup&#231;&#227;o &#233; obtido ap&#243;s um evento coron&#225;rio agudo, agravamento de doen&#231;a pulmonar obstrutiva cr&#244;nica (DPOC) ou doen&#231;a vascular perif&#233;rica sintom&#225;tica e limitante. O aconselhamento m&#233;dico para a cessa&#231;&#227;o do fumo deve ser firme, com &#234;nfase nos benef&#237;cios em curto e m&#233;dio prazos. Pr&#225;ticas agressivas relacionadas &#224; suspens&#227;o do tabagismo devem ser adotadas.<xref ref-type="bibr" rid="B49"><sup>49</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B50"><sup>50</sup></xref> Evid&#234;ncias mostram efic&#225;cia em idosos na utiliza&#231;&#227;o do &#8220;m&#233;todo dos 4 &#8216;A&#8217;&#8221;: averiguar (<italic>ask</italic>); aconselhar (<italic>advise</italic>); ajudar (<italic>assist</italic>); e acompanhar (<italic>arrange follow up</italic>).<xref ref-type="bibr" rid="B51"><sup>51</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B52"><sup>52</sup></xref> Diversas abordagens, tais como interven&#231;&#245;es por meio de aconselhamento individual realizado por profissionais de sa&#250;de, material de autoajuda adequado para a faixa et&#225;ria, utiliza&#231;&#227;o de nicotina (adesivos transd&#233;rmicos ou goma de mascar) ou emprego de medicamento espec&#237;fico (p. ex., bupropiona), v&#234;m se mostrando eficazes no tratamento do tabagismo.<xref ref-type="bibr" rid="B53"><sup>53</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B55"><sup>55</sup></xref></p>
        <table-wrap id="t7">
          <table frame="hsides" rules="groups">
            <colgroup width="33%">
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr>
                <th align="left" valign="middle">Recomenda&#231;&#245;es</th>
                <th align="center" valign="top">Grau de recomenda&#231;&#227;o</th>
                <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top">O tabagismo &#233; fator de risco modific&#225;vel para DCV em idosos e seu abandono &#233; indicado</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">A utiliza&#231;&#227;o de abordagem multidisciplinar, com o m&#233;todo dos 4 &#8220;A&#8221;, &#233; recomend&#225;vel: averiguar (<italic>ask</italic>); aconselhar (<italic>advise</italic>); ajudar (<italic>assist</italic>); e acompanhar (<italic>arrange follow up</italic>)</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">Adesivos transd&#233;rmicos ou goma de mascar de nicotina/bupropiona podem ser utilizados para interrup&#231;&#227;o do tabagismo</td>
                <td align="center" valign="top">IIa</td>
                <td align="center" valign="top">C</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN1a">
              <p><italic>DCV: doen&#231;a cardiovascular</italic>.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>1.7. Obesidade</title>
        <p>A preval&#234;ncia de sobrepeso e obesidade vem aumentando nas &#250;ltimas d&#233;cadas em todas as faixas et&#225;rias, incluindo nos idosos.<xref ref-type="bibr" rid="B56"><sup>56</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B57"><sup>57</sup></xref></p>
        <p>Tanto a obesidade quanto o sobrepeso foram associados a um aumento no risco de mortalidade por todas as causas e por DCV, na popula&#231;&#227;o geral.<xref ref-type="bibr" rid="B58"><sup>58</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B60"><sup>60</sup></xref></p>
        <p>A maioria desses estudos envolveu principalmente pacientes adultos jovens, sendo que esta rela&#231;&#227;o n&#227;o &#233; t&#227;o evidente em idosos.<xref ref-type="bibr" rid="B61"><sup>61</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B64"><sup>64</sup></xref></p>
        <p>Alguns estudos de metan&#225;lise relataram que idosos com sobrepeso e obesidade, quando comparados com idosos com peso dentro da normalidade, tiverem taxa de mortalidade e risco de DCV menor ou nulo. Esse efeito foi chamado de &#8220;paradoxo da obesidade&#8221;.<xref ref-type="bibr" rid="B65"><sup>65</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B67"><sup>67</sup></xref></p>
        <p>Al&#233;m de poss&#237;veis fatores confundidores nesses estudos, outros motivos podem estar envolvidos. O &#237;ndice utilizado para medir e classificar o peso corporal foi o IMC (&#237;ndice de massa corporal). Os graus de obesidade adotados pela Organiza&#231;&#227;o Mundial da Sa&#250;de (OMS), de acordo com o IMC, s&#227;o: sobrepeso (25,0 a 29,9 kg/m<sup>2</sup>) e obesos (acima 30,0 kg/m<sup>2</sup>).<xref ref-type="bibr" rid="B68"><sup>68</sup></xref> Vari&#225;veis como idade, sexo e ra&#231;a podem afetar o IMC. Com o envelhecimento ocorre mudan&#231;a na composi&#231;&#227;o corporal, como aumento da gordura visceral e diminui&#231;&#227;o da massa muscular. Pode ocorrer tamb&#233;m perda de altura por compress&#227;o dos corpos vertebrais ou cifose. Deste modo, o IMC torna-se menos preciso na medida da massa gorda, e ele, isoladamente, pode n&#227;o ser um preditor preciso de risco por DCV em idosos. Por exemplo: alguns idosos podem ser considerados com excesso de peso pelos padr&#245;es de gordura corporal, sem terem um IMC superior a 25 kg/m<sup>2</sup>.</p>
        <p>Utilizando-se apenas o IMC, podemos estar subestimando o grau de adiposidade em indiv&#237;duos que perderam massa muscular. A obesidade central e a nutri&#231;&#227;o s&#227;o fatores que parecem ser de maior import&#226;ncia em rela&#231;&#227;o &#224; mortalidade e o risco DCV nessa popula&#231;&#227;o. Alguns autores sugerem que a circunfer&#234;ncia da cintura (CC) pode ser uma medida particularmente importante para os idosos, melhor do que o IMC para avalia&#231;&#227;o de risco, dada a sua associa&#231;&#227;o com a adiposidade visceral.<xref ref-type="bibr" rid="B69"><sup>69</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B70"><sup>70</sup></xref></p>
        <p>Outro trabalho aponta que mais importante que o IMC nos idosos obesos &#233; a presen&#231;a ou n&#227;o de s&#237;ndrome metab&#243;lica, dividindo essa popula&#231;&#227;o em &#8220;obesos sadios&#8221; (sem s&#237;ndrome metab&#243;lica) e obesos com s&#237;ndrome metab&#243;lica. Esse &#250;ltimo grupo foi fortemente associado ao risco aumentado de DCV independente do IMC.<xref ref-type="bibr" rid="B71"><sup>71</sup></xref></p>
        <p>Mais pesquisas s&#227;o necess&#225;rias para esclarecer a inter-rela&#231;&#227;o de envelhecimento, obesidade, risco cardiovascular e qual(is) o(s) melhor(es) par&#226;metro(s) de medida. O manejo do peso em idosos e os esfor&#231;os para promover o envelhecimento saud&#225;vel devem ter uma abordagem individual, levando-se em considera&#231;&#227;o manuten&#231;&#227;o de massa e for&#231;a muscular, comorbidades, estado funcional, social, atividade f&#237;sica e qualidade de vida. A redu&#231;&#227;o de peso intencional em idosos obesos melhora o perfil de risco cardiovascular, reduz a inflama&#231;&#227;o cr&#244;nica e est&#225; correlacionada a melhora na qualidade de vida. A perda de peso n&#227;o intencional requer uma avalia&#231;&#227;o cl&#237;nica cuidadosa da causa subjacente. Tamb&#233;m a identifica&#231;&#227;o de idosos com obesidade sarcop&#234;nica tem relev&#226;ncia progn&#243;stica. Sarcopenia e obesidade sarcop&#234;nica foram associadas a maior risco de DCV, especialmente em homens idosos com esse tipo de obesidade.</p>
      </sec>
      <sec>
        <title>1.8. Sedentarismo</title>
        <p>A atividade f&#237;sica regular &#233; essencial para o envelhecimento saud&#225;vel. Considerando que o envelhecimento &#233; inevit&#225;vel, o ritmo e a magnitude do decl&#237;nio da fun&#231;&#227;o fisiol&#243;gica podem ser influenciados com uma interven&#231;&#227;o que conste de exerc&#237;cio/atividade f&#237;sica (<xref ref-type="table" rid="t8">Tabela 6</xref>).<xref ref-type="bibr" rid="B72"><sup>72</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B73"><sup>73</sup></xref></p>
        <table-wrap id="t8">
          <label>Tabela 6</label>
          <caption>
            <title>Orienta&#231;&#245;es de exerc&#237;cio do <italic>Centers for Disease Control and Prevention</italic> para idosos acima de 65 anos de idade</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="50%">
              <col/>
              <col/>
            </colgroup>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top" rowspan="2">Benef&#237;cios maiores</td>
                <td align="center" valign="top">2 horas e 30 minutos (150 minutos) de atividade aer&#243;bica de intensidade moderada Atividades de fortalecimento muscular em 2 ou mais dias por semana</td>
              </tr>
              <tr>
                <td align="center" valign="top">1 hora e 15 minutos (75 minutos) de atividade aer&#243;bica de intensidade vigorosa Atividade de fortalecimento muscular em 2 ou mais dias por semana</td>
              </tr>
              <tr>
                <td align="left" valign="top" rowspan="2">Benef&#237;cios ainda maiores</td>
                <td align="center" valign="top">5 horas (300 minutos) por semana de atividade aer&#243;bica de intensidade moderada Atividade de fortalecimento muscular em 2 ou mais dias por semana</td>
              </tr>
              <tr>
                <td align="center" valign="top">2 horas e 30 minutos (150 minutos) de atividade aer&#243;bica de intensidade vigorosa Atividades de fortalecimento muscular em 2 ou mais dias na semana</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN6">
              <p><italic>Adaptado de: Centers for Disease Control and Prevention (CDC). Physical activities for older adults. Dispon&#237;vel em: <ext-link ext-link-type="uri" xlink:href="https://www.cdc.gov/features/activity-older-adults/index.html">www.cdc.gov/features/activity-older-adults/index.html</ext-link>. Acesso em: 18/02/2016</italic>.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>O envelhecimento associa-se &#224; perda da massa muscular esquel&#233;tica, com redu&#231;&#227;o da for&#231;a muscular, flexibilidade, d&#233;bito card&#237;aco e fun&#231;&#227;o pulmonar, mudan&#231;as na regula&#231;&#227;o hormonal e sistema imunol&#243;gico, redu&#231;&#227;o na densidade &#243;ssea e maior preval&#234;ncia e incid&#234;ncia de sedentarismo.<xref ref-type="bibr" rid="B74"><sup>74</sup></xref></p>
        <p>Em pacientes sedent&#225;rios e idosos, a caminhada pode representar uma solu&#231;&#227;o pr&#225;tica, avaliando a frequ&#234;ncia card&#237;aca (FC) antes e ap&#243;s o esfor&#231;o. &#201; preciso reconhecer que idosos n&#227;o representam um grupo uniforme de pacientes e a idade cronol&#243;gica por si s&#243; n&#227;o identifica esse grupo especial.<xref ref-type="bibr" rid="B75"><sup>75</sup></xref></p>
        <p>O sedentarismo &#233; um importante FR para DAC em idosos. Alguns estudos demonstram que o risco relativo de DAC atribu&#237;vel ao sedentarismo &#233; compar&#225;vel ao risco da hipertens&#227;o, hiperlipidemia e tabagismo. O sedentarismo como importante FR est&#225;, na maioria das vezes, associado direta ou indiretamente &#224;s causas ou ao agravamento de v&#225;rias doen&#231;as, tais como obesidade, diabetes, hipertens&#227;o arterial, ansiedade, depress&#227;o, dislipidemia, aterosclerose, doen&#231;a pulmonar, osteoporose e c&#226;ncer.<xref ref-type="bibr" rid="B76"><sup>76</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B77"><sup>77</sup></xref> Exerc&#237;cio f&#237;sico realizado de maneira sistem&#225;tica ajuda no controle da hipertens&#227;o arterial sist&#234;mica (HAS) por redu&#231;&#227;o da resist&#234;ncia arterial perif&#233;rica, aumenta o HDL-c, reduz a obesidade, os triglicer&#237;deos, melhora o controle dos n&#237;veis glic&#234;micos, previne a doen&#231;a coronariana e diminui a mortalidade.<xref ref-type="bibr" rid="B77"><sup>77</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B78"><sup>78</sup></xref></p>
        <p>Al&#233;m disso, melhora a qualidade do sono, a fun&#231;&#227;o cognitiva e a mem&#243;ria de curto prazo, diminui o grau de depress&#227;o, reduz ou atrasa o aparecimento de dem&#234;ncia, reduz risco de c&#226;ncer de c&#243;lon, mama, pr&#243;stata e reto, aumenta a densidade &#243;ssea e diminui o aparecimento de fraturas de f&#234;mur e v&#233;rtebras.<xref ref-type="bibr" rid="B77"><sup>77</sup></xref></p>
        <p>No paciente idoso, a avalia&#231;&#227;o cl&#237;nica pr&#233;-esfor&#231;o e muito importante. O objetivo dos exerc&#237;cios e da reabilita&#231;&#227;o cardiovascular no idoso &#233; melhorar ao m&#225;ximo sua capacidade funcional. Esses objetivos s&#227;o alcan&#231;ados por meio de programas que visam aumentar a capacidade aer&#243;bica, a for&#231;a muscular e a flexibilidade.<xref ref-type="bibr" rid="B72"><sup>72</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B79"><sup>79</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B82"><sup>82</sup></xref></p>
        <p>A quantidade de atividade f&#237;sica deve ser individualizada, considerando as comorbidades e peculiaridades de cada paciente.<xref ref-type="bibr" rid="B73"><sup>73</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B74"><sup>74</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B79"><sup>79</sup></xref></p>
        <p>O idoso deve despender tempo maior de aquecimento pr&#233;-atividade e esfriamento p&#243;s-atividade. A fase de aquecimento inclui exerc&#237;cios de flexibilidade e movimenta&#231;&#227;o, que facilitam a biomec&#226;nica musculoesquel&#233;tica. A fase de esfriamento p&#243;s-exerc&#237;cios permite a dissipa&#231;&#227;o gradual do calor corporal e a consequente vasodilata&#231;&#227;o perif&#233;rica. Les&#245;es musculoesquel&#233;ticas podem ser diminu&#237;das evitando-se atividades de alto impacto, como corrida e pulo. Maior vigil&#226;ncia em atividades com uso de pesos livres, pois o risco de acidentes existe, especialmente em idosos menos habilitados ou mais fragilizados.<xref ref-type="bibr" rid="B72"><sup>72</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B80"><sup>80</sup></xref> Caminhar em intensidade r&#225;pida &#233; uma excelente forma de obter condicionamento f&#237;sico, com aumento gradual do passo e da dist&#226;ncia percorrida.<xref ref-type="bibr" rid="B81"><sup>81</sup></xref> Os idosos devem ser orientados a reduzir a intensidade do exerc&#237;cio em dias &#250;midos ou quentes, pois o fluxo sangu&#237;neo da pele diminui com o envelhecimento, com consequente menor efici&#234;ncia da sudorese e da regula&#231;&#227;o t&#233;rmica.<xref ref-type="bibr" rid="B77"><sup>77</sup></xref> Recomenda-se tamb&#233;m a pr&#225;tica de exerc&#237;cios de resist&#234;ncia pelo menos duas vezes por semana.</p>
        <p>A avalia&#231;&#227;o da pr&#233;-participa&#231;&#227;o deve ser iniciada pela hist&#243;ria e pelo exame cl&#237;nico focado nas peculiaridades dessa popula&#231;&#227;o que, frequentemente, &#233; portadora de doen&#231;a ateroscler&#243;tica silenciosa. A investiga&#231;&#227;o complementar deve ser orientada pelos dados cl&#237;nicos, evitando custos elevados, por vezes proibitivos e desestimulantes para a pr&#225;tica de exerc&#237;cio f&#237;sico. O eletrocardiograma (ECG) de repouso no idoso apresenta limitada aplica&#231;&#227;o como exame de pr&#233;-sele&#231;&#227;o para atividade f&#237;sica.</p>
        <p>O TE deve ser realizado, se poss&#237;vel, em todo idoso antes de iniciar atividade f&#237;sica. A preval&#234;ncia da doen&#231;a coronariana aumenta com a idade, assim, a justificativa para o TE nessa popula&#231;&#227;o pode ser at&#233; maior do que na popula&#231;&#227;o adulta geral.<xref ref-type="bibr" rid="B72"><sup>72</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B79"><sup>79</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B80"><sup>80</sup></xref> O TE &#233; um procedimento no qual o paciente &#233; submetido a um esfor&#231;o programado e individualizado, com a finalidade de se avaliarem as respostas cl&#237;nica, metab&#243;lica, hemodin&#226;mica, auton&#244;mica, eletrocardiogr&#225;fica e, eventualmente, ventilat&#243;ria ao exerc&#237;cio. Nos idosos s&#227;o utilizados protocolos modificados para realiza&#231;&#227;o do TE.<xref ref-type="bibr" rid="B79"><sup>79</sup></xref> Naqueles com contraindica&#231;&#245;es para realiza&#231;&#227;o do TE, deve-se realizar ecocardiograma de estresse ou exame cintilogr&#225;fico. O Holter &#233; utilizado na estratifica&#231;&#227;o de risco em idosos portadores de arritmias detectadas no ECG ou no TE, bem como naqueles com hist&#243;ria de s&#237;ncope.<xref ref-type="bibr" rid="B72"><sup>72</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B82"><sup>82</sup></xref></p>
        <p>A ades&#227;o &#224; atividade f&#237;sica nesse grupo de pessoas tem sido cada vez mais positiva. &#201; preciso sempre pensar que um processo patol&#243;gico ativo ou latente pode estar presente no indiv&#237;duo idoso e que o TE pode contribuir para essa defini&#231;&#227;o.<xref ref-type="bibr" rid="B83"><sup>83</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B84"><sup>84</sup></xref></p>
        <table-wrap id="t9">
          <table frame="hsides" rules="groups">
            <colgroup width="33%">
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr>
                <th align="left" valign="top">Recomenda&#231;&#245;es</th>
                <th align="center" valign="top">Grau de recomenda&#231;&#227;o</th>
                <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top">Exame cl&#237;nico e eletrocardiograma</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">Ecocardiograma, teste de esfor&#231;o ou cintilografia mioc&#225;rdica em paciente de m&#233;dio risco ou em exerc&#237;cio moderado a intenso</td>
                <td align="center" valign="top">IIa</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">Exerc&#237;cio f&#237;sico</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">A</td>
              </tr>
              <tr>
                <td align="left" valign="top">Exerc&#237;cios de resist&#234;ncia</td>
                <td align="center" valign="top">IIa</td>
                <td align="center" valign="top">C</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
      </sec>
      <sec>
        <title>1.9. Dislipidemias em Idosos</title>
        <p>Nos idosos, dislipidemias s&#227;o diagnosticadas frequentemente, principalmente em mulheres, pois os n&#237;veis de LDL-c tendem a subir com o avan&#231;ar da idade, principalmente ap&#243;s a menopausa, enquanto, nos homens, os n&#237;veis de LDL-c tendem a diminuir ap&#243;s 55 anos de idade. Ao contr&#225;rio dos adultos jovens, dislipidemias prim&#225;rias de novo s&#227;o raras, sendo mais frequentes as dislipidemias secund&#225;rias ao hipotireoidismo (principalmente nas mulheres), diabetes melito, intoler&#226;ncia &#224; glicose, s&#237;ndrome nefr&#243;tica, obesidade, alcoolismo ou uso de medicamentos, como diur&#233;ticos tiaz&#237;dicos e bloqueadores beta-adren&#233;rgicos n&#227;o seletivos.<xref ref-type="bibr" rid="B85"><sup>85</sup></xref></p>
        <p>Em rela&#231;&#227;o ao tratamento, sendo os idosos muitas vezes j&#225; de alto risco (devido ao fator idade), na abordagem da dislipidemia deve-se levar mais em considera&#231;&#227;o, quando da decis&#227;o terap&#234;utica, o bom estado geral e mental do paciente, suas condi&#231;&#245;es socioecon&#244;micas, o apoio familiar, as comorbidades presentes e o uso de outros f&#225;rmacos que ir&#227;o influenciar a ades&#227;o e a manuten&#231;&#227;o da terap&#234;utica. Orienta&#231;&#227;o n&#227;o farmacol&#243;gica deve obedecer aos mesmos princ&#237;pios da indicada para adultos jovens, observando-se mais cuidadosamente as necessidades de aporte cal&#243;rico, proteico e vitam&#237;nico e as condi&#231;&#245;es f&#237;sicas para a pr&#225;tica de exerc&#237;cios (recomenda&#231;&#227;o I, evid&#234;ncia B). Deve-se reiterar o abandono dos h&#225;bitos de fumar e de ingest&#227;o excessiva de bebidas alco&#243;licas. Ap&#243;s 90 dias, n&#227;o havendo resposta, f&#225;rmacos podem ser indicados, tomando-se como precau&#231;&#227;o: (1) iniciar sempre com doses mais baixas e aumentar, se necess&#225;rio, progressivamente; (2) analisar a rela&#231;&#227;o custo/benef&#237;cio; e (3) verificar a exist&#234;ncia de condi&#231;&#245;es socioecon&#244;micas para a manuten&#231;&#227;o do tratamento em longo prazo e a realiza&#231;&#227;o de exames cl&#237;nicos e laboratoriais peri&#243;dicos, devido &#224; maior probabilidade de efeitos colaterais e de intera&#231;&#245;es medicamentosas.<xref ref-type="bibr" rid="B85"><sup>85</sup></xref></p>
        <p>Para a hipercolesterolemia, as estatinas s&#227;o a primeira escolha.<xref ref-type="bibr" rid="B86"><sup>86</sup></xref> A toler&#226;ncia &#233; boa, n&#227;o h&#225; maior incid&#234;ncia de efeitos indesej&#225;veis, embora dores musculares, c&#227;ibras, fraqueza, por vezes confundidas com doen&#231;a osteomuscular, possam ocorrer, mesmo com doses baixas. Evid&#234;ncias da an&#225;lise de subgrupos de estudos de preven&#231;&#227;o prim&#225;ria e secund&#225;ria e o estudo <italic>Pravastatin in Elderly Individuals at Risk of Vascular Disease</italic> (PROSPER),<xref ref-type="bibr" rid="B87"><sup>87</sup></xref> especialmente delineado para idosos com ou sem manifesta&#231;&#227;o pr&#233;via de aterosclerose, demonstraram os benef&#237;cios do tratamento para essa faixa et&#225;ria: redu&#231;&#227;o de eventos coron&#225;rios (recomenda&#231;&#227;o IIa, evid&#234;ncia B), AVE (grau de recomenda&#231;&#227;o IIa, n&#237;vel de evid&#234;ncia B), preserva&#231;&#227;o de fun&#231;&#245;es cognitivas (grau de recomenda&#231;&#227;o IIb, n&#237;vel de evid&#234;ncia B). Quando as doses m&#225;ximas das estatinas n&#227;o s&#227;o suficientes para se atingirem as metas preconizadas de LDL-c, pode-se associar a ezetimiba &#224;s estatinas (grau de recomenda&#231;&#227;o IIb, n&#237;vel de evid&#234;ncia B).<xref ref-type="bibr" rid="B88"><sup>88</sup></xref></p>
        <p>Na hipertrigliceridemia, empregam-se os fibratos (se n&#227;o houver calculose biliar e insufici&#234;ncia renal). Fibratos e estatinas podem ser associados se houver dislipidemia mista (LDL-c e triglicer&#237;deos elevados), principalmente com HDL-c reduzido (grau de recomenda&#231;&#227;o IIb, n&#237;vel de evid&#234;ncia D).<xref ref-type="bibr" rid="B88"><sup>88</sup></xref></p>
        <p>Nas dislipidemias secund&#225;rias, o cuidado fundamental &#233; o tratamento da doen&#231;a desencadeante e a substitui&#231;&#227;o ou retirada de medicamentos indutores. Devemos lembrar que os idosos, em geral, utilizam outros f&#225;rmacos metabolizados no citocromo P450 (CYP450) com possibilidade de intera&#231;&#227;o com os hipolipemiantes, alterando sua concentra&#231;&#227;o s&#233;rica (grau de recomenda&#231;&#227;o IIb, n&#237;vel de evid&#234;ncia D).<xref ref-type="bibr" rid="B88"><sup>88</sup></xref></p>
      </sec>
      <sec>
        <title>1.10. Depress&#227;o e Doen&#231;a Cardiovascular</title>
        <p>Depress&#227;o e ansiedade s&#227;o altamente prevalentes em indiv&#237;duos com DAC e outras DCV. T&#234;m sido consideradas ainda fatores de risco independentes para DAC e DCV, al&#233;m de alterarem a sua hist&#243;ria natural.<xref ref-type="bibr" rid="B89"><sup>89</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B90"><sup>90</sup></xref></p>
        <p>A depress&#227;o &#233; desproporcionalmente mais frequente entre pacientes portadores de DAC, com preval&#234;ncia entre 20% e 40%. Relata-se ainda que a depress&#227;o est&#225; associada prospectivamente a um risco aumentado de desenvolvimento de DAC durante a vida,<xref ref-type="bibr" rid="B91"><sup>91</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B92"><sup>92</sup></xref> inclusive IAm<sup>93</sup> e mortalidade.<xref ref-type="bibr" rid="B94"><sup>94</sup></xref> Estudo de seguimento por 60 meses de 158 pacientes que sofreram IAM revelou que a depress&#227;o maior era preditor significativo de mortalidade e eventos card&#237;acos adversos.<xref ref-type="bibr" rid="B95"><sup>95</sup></xref></p>
        <p>Efeitos colaterais dos antidepressivos sobre o sistema cardiovascular foram relatados, incluindo bradicardia, taquicardia, hipertens&#227;o, hipotens&#227;o, hipotens&#227;o ortost&#225;tica (HO), altera&#231;&#245;es no ECG, altera&#231;&#245;es eletrol&#237;ticas, redu&#231;&#227;o da condu&#231;&#227;o card&#237;aca e arritmias e morte s&#250;bita card&#237;aca.<xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
        <sec>
          <title>1.10.1. Tratamento da Depress&#227;o e da Ansiedade na Doen&#231;a Cardiovascular</title>
          <p>Os antidepressivos de primeira gera&#231;&#227;o incluem IMAO e antidepressivos tric&#237;clicos (ADT)/tetrac&#237;clicos (ATC); os antidepressivos de segunda gera&#231;&#227;o incluem inibidores seletivos da recapta&#231;&#227;o de serotonina (ISRS), inibidores da recapta&#231;&#227;o seletiva de norepinefrina (IRSN) e antidepressivos at&#237;picos.<xref ref-type="bibr" rid="B89"><sup>89</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
          <p>IMAO (fenelzina, tranilcipromina, moclobemida, selegilina etc.) &#8211; Embora sejam eficazes, apresentam v&#225;rios efeitos colaterais desfavor&#225;veis, principalmente HO, taquicardia e crises hipertensivas, estas &#250;ltimas associadas inclusive a AVE e dissec&#231;&#227;o aguda da aorta e, portanto, devem ser evitados nos pacientes com DAC.<xref ref-type="bibr" rid="B89"><sup>89</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
          <p>ADT (imipramina, amitriptilina, nortriptilina, desipramina, clomipramina, doxepina, maprotilina etc.) &#8211; Seus efeitos colaterais cardiovasculares s&#227;o bastante reconhecidos: aumento da FC, HO, retardo da condu&#231;&#227;o card&#237;aca e incremento da variabilidade do intervalo QT.<xref ref-type="bibr" rid="B89"><sup>89</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B97"><sup>97</sup></xref> Tais efeitos, que foram relatados n&#227;o s&#243; em pacientes com DCV mas tamb&#233;m em pessoas sem antecedentes de doen&#231;as card&#237;acas, somados &#224; sua a&#231;&#227;o anticolin&#233;rgica, tornam esta classe inapropriada para tratamento de depress&#227;o em pacientes idosos.<xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
          <p>Inibidores seletivos da recapta&#231;&#227;o de serotonina (ISRS) (fluoxetina, sertralina, paroxetina, citalopram, escitalopram, fluvoxamina etc.) &#8211; S&#227;o considerados os medicamentos de escolha no tratamento da depress&#227;o e ansiedade na maioria dos casos devido a seu perfil de seguran&#231;a aceit&#225;vel e maiores margens de n&#237;veis n&#227;o t&#243;xicos em compara&#231;&#227;o com outras classes de antidepressivos.<xref ref-type="bibr" rid="B89"><sup>89</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
          <p>Com rela&#231;&#227;o &#224; efic&#225;cia dos ISRS na diminui&#231;&#227;o dos sintomas depressivos, todas as metan&#225;lises de indicadores selecionados mostraram que antidepressivos s&#227;o mais eficazes que placebo.<xref ref-type="bibr" rid="B98"><sup>98</sup></xref></p>
          <p>Os ISRS podem causar prolongamento do intervalo QT (relatado principalmente com fluoxetina e citalopram), mas geralmente n&#227;o levam a arritmias com risco &#224; vida em doses terap&#234;uticas. Entre os ISRS, o citalopram parece ser mais cardiot&#243;xico (dist&#250;rbios de condu&#231;&#227;o e arritmias).<xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
          <p>A maioria dos casos do prolongamento de intervalo QT e subsequente <italic>torsade de pointes</italic> (TdP) induzidos por ISRS s&#227;o observados em pacientes com vulnerabilidades subjacentes como a s&#237;ndrome QT longo cong&#234;nito, IAM recente, hipocalemia, hipomagnesemia, ou em caso de sobredosagem da subst&#226;ncia.<xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
          <p>Nesta classe h&#225; algumas evid&#234;ncias de que o escitalopram e a sertralina tenham o melhor equil&#237;brio entre efic&#225;cia e aceitabilidade para o tratamento farmacol&#243;gico da depress&#227;o em pacientes card&#237;acos.<xref ref-type="bibr" rid="B99"><sup>99</sup></xref></p>
          <p>Em resumo, os ISRS provavelmente n&#227;o causam efeitos adversos quando utilizados nas dosagens recomendadas e tem se sugerido que eles possam trazer alguns benef&#237;cios para o sistema cardiovascular por interm&#233;dio de mecanismos complexos, como menores taxas de IAM em compara&#231;&#227;o com os outros tipos de antidepressivos, particularmente ADT.<xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
          <p>Como ainda n&#227;o h&#225; orienta&#231;&#227;o cl&#237;nica robusta, os pacientes devem ser individualizados em rela&#231;&#227;o aos seus potenciais riscos e benef&#237;cios e estudos adicionais s&#227;o necess&#225;rios para verificar o perfil preciso de seguran&#231;a cardiovascular.<xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
          <p>Inibidores seletivos da recapta&#231;&#227;o de serotonina e norepinefrina (ISRSN) (venlafaxina, desvenlafaxina, reboxetina, duloxetina etc.) &#8211; A venlafaxina est&#225; associada a cardiotoxicidade grave apenas se administrada em altas doses. A fal&#234;ncia ventricular esquerda, mesmo em pacientes sem hist&#243;ria de DCV pr&#233;via, tamb&#233;m &#233; relatada na literatura.<xref ref-type="bibr" rid="B89"><sup>89</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B96"><sup>96</sup></xref> &#201; recomendado que a press&#227;o arterial (PA) de pacientes que fazem uso de ISRSN (particularmente venlafaxina) seja monitorada, visto que a eleva&#231;&#227;o desta tem sido relatada em estudos epidemiol&#243;gicos.<xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
          <p>Antidepressivos at&#237;picos (mirtazapina, agomelatina, nefazodona, trazodona, etc.) &#8211; Mirtazapina em altas doses pode causar hipotens&#227;o e afetar a FC. Trazodona tem m&#237;nima atividade colin&#233;rgica, pode causar HO e, em excesso, prolongamento do QT e retardo da condu&#231;&#227;o atrioventricular.<xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
          <p>Al&#233;m do tratamento farmacol&#243;gico, s&#227;o indicadas psicoterapia e prescri&#231;&#227;o de terapias n&#227;o medicamentosas que melhorem o progn&#243;stico e a qualidade de vida do paciente, al&#233;m de diminuir os riscos da evolu&#231;&#227;o da DAC e da DCV, como atividade f&#237;sica, principalmente o exerc&#237;cio aer&#243;bico e a reabilita&#231;&#227;o card&#237;aca.<xref ref-type="bibr" rid="B89"><sup>89</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B99"><sup>99</sup></xref></p>
        </sec>
      </sec>
      <sec>
        <title>1.11. Outros Fatores de Risco Cardiovascular</title>
        <p>Os FR tradicionais explicariam apenas a metade dos casos de DCV, as quais apresentam altas taxas de morbi/mortalidade. V&#225;rios estudos t&#234;m sido desenvolvidos na busca de poss&#237;veis novos fatores de risco, ditos FR emergentes, bem como no diagn&#243;stico precoce da DCV por meio da busca de sinais de aterosclerose subcl&#237;nica. Dentre os FR emergentes ser&#227;o abordados nesta Diretriz hiperuricemia, prote&#237;na C reativa (PC-R), vitamina D, fatores gen&#233;ticos, escore de c&#225;lcio coron&#225;rio (ECC) e pesquisa de aterosclerose subcl&#237;nica.</p>
        <sec>
          <title>1.11.1. Hiperuricemia</title>
          <p>Recentes estudos epidemiol&#243;gicos v&#234;m demonstrando que a hiperuricemia foi frequentemente observada em pacientes com DCV ou em alto risco, como hipertens&#227;o arterial, DAC, doen&#231;a vascular perif&#233;rica, IC, AVE.<xref ref-type="bibr" rid="B100"><sup>100</sup></xref></p>
          <p>Metan&#225;lise recente de estudos observacionais prospectivos para hiperuricemia e risco de AVE demonstrou um aumento significativo do risco de incid&#234;ncia de AVE e mortalidade com base em estudos que ajustaram os FR tradicionais de AVE, como idade, sexo, hipertens&#227;o, hipercolesterolemia e glicose s&#233;rica.&#160;V&#225;rios mecanismos fisiopatol&#243;gicos foram postulados, incluindo disfun&#231;&#227;o endotelial, metabolismo oxidativo, adesividade de plaquetas e agrega&#231;&#227;o. No entanto, o papel da hiperuricemia como FR independente para DAC permanece controverso.<xref ref-type="bibr" rid="B101"><sup>101</sup></xref></p>
        </sec>
        <sec>
          <title>1.11.2. Prote&#237;na C Reativa</title>
          <p>O papel da inflama&#231;&#227;o na propaga&#231;&#227;o da aterosclerose e suscetibilidade a eventos cardiovasculares est&#225; bem estabelecido.&#160;Embora a PC-R esteja envolvida no processo imunol&#243;gico que desencadeia o remodelamento vascular e a deposi&#231;&#227;o de placas e esteja associada a risco aumentado de DCV, n&#227;o existe evid&#234;ncia definitiva para seu papel como fator causal na aterotrombose. O Estudo J&#250;piter analisou 9.261 idosos de ambos os sexos conforme o n&#237;vel da PC-R ultrassens&#237;vel (PC-R-US) para receber ou n&#227;o rosuvastatina, sendo os resultados encontrados semelhantes aos dos indiv&#237;duos mais jovens, nos quais ocorreu redu&#231;&#227;o de eventos cardiovasculares.<xref ref-type="bibr" rid="B102"><sup>102</sup></xref></p>
          <p>Apesar da publica&#231;&#227;o de diretrizes sobre o uso de PC-R-US na predi&#231;&#227;o de risco de DCV por v&#225;rias organiza&#231;&#245;es profissionais, h&#225; falta de consenso claro quanto ao uso cl&#237;nico &#243;timo de PC-R-US.<xref ref-type="bibr" rid="B103"><sup>103</sup></xref></p>
        </sec>
        <sec>
          <title>1.11.3. Vitamina D</title>
          <p>Recentes estudos evidenciam forte associa&#231;&#227;o entre hipovitaminose D e presen&#231;a de HAS, s&#237;ndrome metab&#243;lica, diabetes e aterosclerose, sendo considerado um FR emergente para DCV.<xref ref-type="bibr" rid="B104"><sup>104</sup></xref></p>
          <p>Os mecanismos pelos quais a vitamina D exerceria seu papel protetor cardiovascular ainda n&#227;o est&#227;o bem estabelecidos. No NHANES III (Third National Health and Nutrition Examination Survey), que envolveu 3.408 pacientes idosos acompanhados por 7 anos, ap&#243;s ajuste para risco cardiovascular, esta&#231;&#227;o do ano e dados demogr&#225;ficos verificou-se que n&#237;veis de vitamina D estavam associados negativamente com risco de mortalidade, sendo que esta associa&#231;&#227;o era mais forte para mortalidade cardiovascular.<xref ref-type="bibr" rid="B105"><sup>105</sup></xref></p>
          <p>Em metan&#225;lise com 19 estudos prospectivos com mais de 65 mil pacientes ficou demonstrado que o risco para todas as DCV, bem como morte cardiovascular e DAC, foi menor naqueles pacientes com n&#237;veis mais elevados de vitamina D.<xref ref-type="bibr" rid="B106"><sup>106</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B107"><sup>107</sup></xref></p>
        </sec>
        <sec>
          <title>1.11.4. Fatores Gen&#233;ticos</title>
          <p>O envelhecimento &#233; caracterizado pela intera&#231;&#227;o complexa de mecanismos celulares e moleculares que leva a uma cole&#231;&#227;o de problemas funcionais. Tais problemas est&#227;o intimamente associados uns com os outros e incluem vasodilata&#231;&#227;o piorada, aumento da rigidez arterial e remodela&#231;&#227;o evidente da matriz extracelular, espessamento mediointimal difuso das car&#243;tidas e endot&#233;lio disfuncional.&#160;Os mecanismos por meio dos quais a idade realmente contribui para o risco cardiovascular continuam a ser objeto de especula&#231;&#227;o. Embora esse paradigma explique o envelhecimento vascular, considerando os FR cl&#225;ssicos como mecanismos causais, surgiu uma vis&#227;o alternativa recentemente proposta sobre o envelhecimento vascular, que apresenta novas alternativas mecanicistas para a compreens&#227;o do processo de envelhecimento vascular.&#160;Neste novo paradigma, mecanismos causais para o processo de envelhecimento em si, mais notavelmente a instabilidade gen&#244;mica, incluindo o desgaste dos tel&#244;meros, impulsionam as mudan&#231;as prejudiciais que ocorrem cada vez mais com o envelhecimento biol&#243;gico.<xref ref-type="bibr" rid="B108"><sup>108</sup></xref></p>
        </sec>
        <sec>
          <title>1.11.5. Escore de C&#225;lcio Coron&#225;rio</title>
          <p>Representa um importante marcador de risco de eventos cardiovasculares, especialmente para predizer risco de IAM nos anos subsequentes, sendo que escore zero demonstra possibilidade quase nula de ocorr&#234;ncia de evento coronariano nos anos subsequentes. Por&#233;m, escore de c&#225;lcio acima de 100 &#233; considerado agravante de risco e acima de 400 indica alto risco para eventos coronarianos.<xref ref-type="bibr" rid="B109"><sup>109</sup></xref></p>
          <table-wrap id="t10">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top">Recomenda&#231;&#245;es</th>
                  <th align="center" valign="top">Grau de recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Escore de c&#225;lcio coron&#225;rio</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
        </sec>
        <sec>
          <title>1.11.6. Pesquisa de Aterosclerose Subcl&#237;nica</title>
          <p>&#201; indicada para melhor estratifica&#231;&#227;o do risco cardiovascular em idosos, tendo em vista a melhor identifica&#231;&#227;o de casos que necessitar&#227;o de terapias mais agressivas. O Cardiovascular Health Study acompanhou idosos por 10 anos e demonstrou que o &#237;ndice de aterosclerose subcl&#237;nica foi melhor preditor de eventos cardiovasculares que os FR tradicionais em idosos assintom&#225;ticos. Este &#237;ndice &#233; composto por &#237;ndice tornozelo-braquial (ITB), estenose de art&#233;ria car&#243;tida, espessura do complexo &#237;ntima-m&#233;dia da car&#243;tida, altera&#231;&#245;es no eletro e no ecocardiograma, resposta positiva ao question&#225;rio de Rose e ao question&#225;rio de claudica&#231;&#227;o intermitente.<xref ref-type="bibr" rid="B110"><sup>110</sup></xref> A ultrassonografia de art&#233;rias car&#243;tidas representa um importante recurso na avalia&#231;&#227;o dos pacientes idosos. Pacientes com 50% ou mais de obstru&#231;&#227;o de car&#243;tida s&#227;o considerados de alto risco para eventos coron&#225;rios.<xref ref-type="bibr" rid="B111"><sup>111</sup></xref></p>
          <table-wrap id="t11">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top">Recomenda&#231;&#245;es</th>
                  <th align="center" valign="top">Grau de recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Pesquisa de aterosclerose subcl&#237;nica</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
          <sec>
            <title>1.11.6.1 &#205;ndice Tornozelo-Braquial</title>
            <p>A doen&#231;a arterial obstrutiva perif&#233;rica (DAOP) est&#225; fortemente relacionada a eventos coron&#225;rios e pode ser avaliada pelo ITB, um exame de baixo custo e f&#225;cil aplicabilidade. ITB &lt; 0,9 associa-se positivamente a maior n&#250;mero de eventos coronarianos e morte de etiologia cardiovascular e sua indica&#231;&#227;o se aplica sempre que existirem altera&#231;&#245;es no exame cl&#237;nico sugestivas de doen&#231;a arterial perif&#233;rica, bem como para descartar claudica&#231;&#227;o intermitente (grau de recomenda&#231;&#227;o IIa, n&#237;vel de evid&#234;ncia C). As recomenda&#231;&#245;es de recentes diretrizes americanas destacam a associa&#231;&#227;o forte e consistente de idade avan&#231;ada com preval&#234;ncia e incid&#234;ncia de DAOP.&#160;A idade &gt; 70 anos &#233; um FR independente para o desenvolvimento de DAOP envolvendo as extremidades inferiores, a despeito de outros fatores de risco, com taxas de preval&#234;ncia &gt; 20% em homens e mulheres nessa faixa et&#225;ria.&#160;Dado o forte efeito da idade na preval&#234;ncia de DAOP, as diretrizes endossam o ITB como uma recomenda&#231;&#227;o de Classe I (n&#237;vel de evid&#234;ncia C).<xref ref-type="bibr" rid="B112"><sup>112</sup></xref></p>
          </sec>
        </sec>
      </sec>
      <sec>
        <title>1.12. Doen&#231;a de Aorta e de Car&#243;tidas</title>
        <sec>
          <title>1.12.1. Aneurisma de Aorta Tor&#225;cica</title>
          <p>A valva a&#243;rtica bic&#250;spide (VAB) &#233; a modalidade mais frequente de cardiopatia cong&#234;nita (1% a 2%), e pode cursar com aneurisma de aorta tor&#225;cica (AAT) de alto risco para sofrer expans&#227;o. At&#233; 50% dos pacientes com VAB desenvolvem dilata&#231;&#227;o da aorta ascendente. Entre os fatores que contribuem para a progress&#227;o do AAT na presen&#231;a de HAS est&#227;o a obesidade e o aumento da idade. Como essas tr&#234;s condi&#231;&#245;es frequentemente se apresentam juntas no idoso, o AAT tem sido subdiagnosticado nessa faixa et&#225;ria. Estima-se que o AAT esteja presente em pelo menos 3% a 4% dos idosos.</p>
          <p>Pacientes com AAT encontram-se em preven&#231;&#227;o prim&#225;ria. Uma das complica&#231;&#245;es do AAT &#233; a dissec&#231;&#227;o aguda, que tem frequ&#234;ncia duas vezes maior no homem que na mulher. No entanto, a ruptura &#233; respons&#225;vel por 60% das mortes atribu&#237;das ao AAT.</p>
          <p>As diretrizes atuais consideram que o ponto de corte para indica&#231;&#227;o de cirurgia no AAT ascendente &#233; 5,5 cm para pacientes sem Marfan ou VAB, e 5,0 cm na presen&#231;a dessas duas &#250;ltimas condi&#231;&#245;es cl&#237;nicas (<xref ref-type="table" rid="t12">Tabela 7</xref>). AAT com di&#226;metro &#8805; 4 cm requer mensura&#231;&#227;o anual, preferencialmente por meio de angiotomografia (padr&#227;o-ouro, mas sujeito a radia&#231;&#227;o) ou angiorresson&#226;ncia magn&#233;tica. A partir de 5 cm, no AAT n&#227;o gen&#233;tico, a mensura&#231;&#227;o deve ser semestral. O ecocardiograma tende a subestimar o calibre da aorta.<xref ref-type="bibr" rid="B113"><sup>113</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B116"><sup>116</sup></xref></p>
          <table-wrap id="t12">
            <label>Tabela 7</label>
            <caption>
              <title>Di&#226;metro a partir do qual a cirurgia de aneurisma de aorta est&#225; indicada, de acordo com as diretrizes atuais</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top">Aorta</th>
                  <th align="center" valign="top">Marfan/VAB</th>
                  <th align="center" valign="top">N&#227;o Marfan</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Ascendente</td>
                  <td align="center" valign="top">5,0 cm</td>
                  <td align="center" valign="top">5,5 cm</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Descendente</td>
                  <td align="center" valign="top">6,0 cm</td>
                  <td align="center" valign="top">6,5 cm</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN7">
                <p><italic>VAB: valva a&#243;rtica bic&#250;spide</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>A mortalidade da cirurgia eletiva do AAT em centros altamente especializados &#233; de 2,9%. O risco de AVE ou paraplegia &#233; bem maior na aorta descendente. Nesse &#250;ltimo territ&#243;rio, a op&#231;&#227;o pela interven&#231;&#227;o endovascular, com coloca&#231;&#227;o de stent, apresenta menor risco de paraplegia.</p>
        </sec>
        <sec>
          <title>1.12.2. Aneurisma de Aorta Abdominal</title>
          <p>O aneurisma de aorta abdominal (AAA) acomete preferencialmente pessoas idosas (&#8805; 65 anos), e &#233; de natureza ateroscler&#243;tica; desse modo, o AAA posiciona o paciente na preven&#231;&#227;o secund&#225;ria. O AAA tem no tabagismo seu principal fator etiol&#243;gico, e &#233; 3 a 5 vezes mais frequente no fumante do que no n&#227;o fumante. O AAA &#233; tamb&#233;m comum no paciente com doen&#231;a arterial perif&#233;rica (DAP).<xref ref-type="bibr" rid="B115"><sup>115</sup></xref></p>
          <p>O AAA &#233; encontrado em 1,3% dos homens com idade entre 45 e 54 anos, e em 12,5% daqueles na faixa et&#225;ria entre 75 e 84 anos. Nas mulheres, a preval&#234;ncia m&#225;xima foi de 5,2% nas idosas, sendo de 0% nas jovens. Provavelmente, o fato de o homem fumar bem mais que a mulher contribua para essa marcante diferen&#231;a de preval&#234;ncia por faixa et&#225;ria entre os g&#234;neros. Todavia, a evolu&#231;&#227;o e o progn&#243;stico do AAA s&#227;o piores no sexo feminino.<xref ref-type="bibr" rid="B113"><sup>113</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B115"><sup>115</sup></xref></p>
          <p>Recomenda-se a avalia&#231;&#227;o discriminativa inicial por meio da ultrassonografia, principalmente para pacientes do sexo masculino que tenham sido fumantes, a partir da idade de 65 anos. Caso o resultado seja normal, n&#227;o h&#225; necessidade de reavalia&#231;&#227;o peri&#243;dica.<xref ref-type="bibr" rid="B113"><sup>113</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B115"><sup>115</sup></xref></p>
          <p>AAA com di&#226;metro &#8805; 4 cm requer mensura&#231;&#227;o anual, que pode ser feita apenas por ultrassonografia abdominal, a qual, nesse territ&#243;rio, apresenta excelentes sensibilidade e especificidade. A partir de 5 cm, o rastreamento deve ser semestral. O ponto de corte para indicar a interven&#231;&#227;o &#233; 5,5 cm. A cirurgia a c&#233;u aberto tem maior risco, mas apresenta maior durabilidade, e deve ser indicada preferencialmente para indiv&#237;duos mais jovens, com maior expectativa de vida. A interven&#231;&#227;o endovascular tem evolu&#237;do bastante e deve ser indicada preferencialmente para pacientes mais idosos ou considerados de alto risco cir&#250;rgico.<xref ref-type="bibr" rid="B113"><sup>113</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B116"><sup>116</sup></xref></p>
          <sec>
            <title>1.12.2.1. Car&#243;tidas</title>
            <p>N&#227;o existe evid&#234;ncia s&#243;lida da eventual vantagem do tratamento intervencionista sobre o controle cl&#237;nico intensivo dos FR cardiovasculares, especialmente se considerarmos o uso de estatinas de &#250;ltima gera&#231;&#227;o em doses plenas, embora muitos servi&#231;os optem pelo tratamento agressivo, apenas com base em registros e na opini&#227;o de especialistas.<xref ref-type="bibr" rid="B117"><sup>117</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B118"><sup>118</sup></xref></p>
            <p>A ultrassonografia de car&#243;tidas est&#225; indicada de rotina apenas para pacientes que tenham sofrido AVE/ataque isqu&#234;mico transit&#243;rio (AIT), ou ainda quando for identificada, ao exame f&#237;sico, diminui&#231;&#227;o, aus&#234;ncia ou assimetria de pulso, ou sopro carot&#237;deo.</p>
          </sec>
        </sec>
        <sec>
          <title>1.12.3. Estudo CREST Original e 10 Anos Depois</title>
          <p>O estudo Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) original (n = 2.502) visou observar de forma comparativa a redu&#231;&#227;o do risco de AVE isqu&#234;mico em m&#233;dio e longo prazos, proporcionada pela endarterectomia carot&#237;dea (EAC) e a angioplastia com <italic>stent</italic> em car&#243;tida (ASC) em pacientes com doen&#231;a ateroscler&#243;tica carot&#237;dea significativa. A propor&#231;&#227;o de assintom&#225;ticos cerebrovasculares e dos que haviam sofrido AVE/AIT foi muito similar. O objetivo principal foi avaliar o risco de morte, IAM ou AVE at&#233; 30 dias ap&#243;s o procedimento, e de AVE ipsolateral nos quatro anos seguintes. Faltou, no entanto, um bra&#231;o de tratamento cl&#237;nico otimizado. O risco de AVE menor foi maior no grupo ASC aos 30 dias, ao passo que o de IAM foi mais elevado no bra&#231;o EAC. Ao final de quatro anos, o risco de AVE foi baixo e similar em ambos os bra&#231;os em an&#225;lise (2,0% e 2,4%; p = 0,85). A principal conclus&#227;o foi que tanto a EAC como a ASC podem ser alternativamente indicadas para o tratamento intervencionista carot&#237;deo. Achados adicionais sugeriram que a EAC parece beneficiar mais os idosos, ao passo que a ASC seria mais &#250;til em subpopula&#231;&#245;es &lt; 65 anos.<xref ref-type="bibr" rid="B117"><sup>117</sup></xref></p>
          <p>A maior li&#231;&#227;o do CREST 10 anos foi que, uma vez ultrapassada a fase cr&#237;tica inicial, o paciente submetido a tratamento intervencionista tende a evoluir muito bem em longo prazo. O risco de AVE em 10 anos foi de 6,9% no bra&#231;o ASC e de 5,6% no grupo EAC, sem diferen&#231;a estat&#237;stica significante (p = 0,96). O objetivo prim&#225;rio composto (morte, IAM e AVE) ocorreu em 11,8% dos participantes do grupo ASC e em 9,9% dos randomizados para EAC, sem diferen&#231;a estat&#237;stica (p = 0,51). Contudo, o objetivo composto morte/AVE em 10 anos foi pior no grupo ASC (11,0% vs. 7,9%; raz&#227;o de chances [RC]: 1,37%; p = 0,04).<xref ref-type="bibr" rid="B118"><sup>118</sup></xref></p>
          <p>O estudo ACT 1 (n = 1.453) incluiu pacientes com doen&#231;a carot&#237;dea significativa assintom&#225;tica randomizados para tratamento intervencionista por EAC (n = 364; 25%) ou ASC (n = 1.089; 75%). Foram exclu&#237;dos os idosos &gt;80 anos e os que haviam sofrido AVE/AIT nos &#250;ltimos 180 dias. O padr&#227;o anat&#244;mico carot&#237;deo teria que ser vi&#225;vel para ambos os procedimentos, e o grau m&#237;nimo de 70% de estenose seria diagnosticado por ultrassonografia ou angiografia.<xref ref-type="bibr" rid="B119"><sup>119</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B120"><sup>120</sup></xref></p>
          <p>O objetivo principal foi demonstrar a n&#227;o inferioridade da ASC sobre a EAC em rela&#231;&#227;o a um desfecho composto, representado por morte IAM e AVE nos primeiros 30 dias, e de AVC ipsolateral em um ano. Os resultados de 30 dias mostraram que a incid&#234;ncia desse desfecho foi de apenas 2,95%. Ocorreram mais casos de AVE e de morte ou AVE no bra&#231;o ASC, e de IAM no subgrupo EAC. O risco de AVE maior foi baixo (0,4%) e a mortalidade foi de 0,2%. A sobrevida de m&#233;dio e longo prazos livre de AVE foi excelente em ambos os bra&#231;os, sendo de 97,5% em um ano e de 93,9% em cinco anos. Em cinco anos, 97,5% dos participantes n&#227;o necessitaram de reinterven&#231;&#227;o em car&#243;tida, e a mortalidade total foi de 11,8%.<xref ref-type="bibr" rid="B119"><sup>119</sup></xref></p>
        </sec>
        <sec>
          <title>1.12.4. Cuidados e Recomenda&#231;&#245;es</title>
          <p>O grande problema do tratamento intervencionista carot&#237;deo est&#225; no risco de morte, IAM ou AVE inerente aos procedimentos per se, que se estende por 30 dias ap&#243;s a interven&#231;&#227;o. Superada essa fase, o risco anual de AVE ou de necessidade de reinterven&#231;&#227;o &#233; considerado baixo.</p>
          <p>A interven&#231;&#227;o por EAC ou ASC em pacientes com doen&#231;a carot&#237;dea assintom&#225;tica n&#227;o apresenta base s&#243;lida de indica&#231;&#227;o, em compara&#231;&#227;o com o tratamento cl&#237;nico otimizado, e deve preferencialmente ser evitada neste momento, at&#233; que estudos em andamento possam ajudar a resolver de forma definitiva essa importante quest&#227;o (CREST 2 e ACST2).<xref ref-type="bibr" rid="B121"><sup>121</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B123"><sup>123</sup></xref></p>
          <p>Mais de 90% das interven&#231;&#245;es carot&#237;deas nos EUA atualmente envolvem pacientes assintom&#225;ticos cerebrovasculares. Na Alemanha e It&#225;lia esses &#237;ndices s&#227;o de 60%, na Austr&#225;lia e Canad&#225; de 15%, e na Dinamarca de 0%.</p>
          <p>O risco anual de AVE em assintom&#225;ticos com doen&#231;a carot&#237;dea significativa tratados apenas clinicamente tem alcan&#231;ado um valor t&#227;o baixo quanto 0,5%, ou seja, os mesmos &#237;ndices documentados nos estudos ACT1 e CREST em 5 e 10 anos, respectivamente.<xref ref-type="bibr" rid="B122"><sup>122</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B123"><sup>123</sup></xref></p>
          <p>Ao contr&#225;rio do que t&#234;m admitido algumas diretrizes, sugere-se que o tratamento intervencionista carot&#237;deo seja reservado para pacientes sintom&#225;ticos (AVE/AIT h&#225; &lt; 6 meses) e, em assintom&#225;ticos, somente seja indicado quando o grau de estenose for de 70% a 99%, a despeito do tratamento cl&#237;nico otimizado, e houver comprova&#231;&#227;o da exist&#234;ncia de grande &#225;rea cerebral sob risco, ou de microembolia relacionada &#224; placa, por meio de exames de imagem e de avalia&#231;&#227;o de fluxo sangu&#237;neo cerebral.<xref ref-type="bibr" rid="B121"><sup>121</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B123"><sup>123</sup></xref></p>
        </sec>
      </sec>
      <sec>
        <title>1.13. Avalia&#231;&#227;o de Risco Cir&#250;rgico em Pacientes Idosos</title>
        <p>A popula&#231;&#227;o de idosos &#233; a que mais cresce na atualidade e, por esta raz&#227;o, tem sido observado um significativo aumento no n&#250;mero de procedimentos cir&#250;rgicos neste grupo et&#225;rio. Estima-se que o n&#250;mero de procedimentos cir&#250;rgicos em pessoas acima de 65 anos seja 4 vezes maior do que na popula&#231;&#227;o mais jovem.<xref ref-type="bibr" rid="B124"><sup>124</sup></xref> A preval&#234;ncia de DCV, sintom&#225;tica ou assintom&#225;tica, cresce progressivamente com a idade, como &#233; evidenciado nos resultados de muitos estudos a sugerir que idade &#8805; 80 anos seja um preditor independente de complica&#231;&#245;es peroperat&#243;rias e morte em pacientes submetidos a cirurgia n&#227;o card&#237;aca ou card&#237;aca.<xref ref-type="bibr" rid="B125"><sup>125</sup></xref> No entanto, s&#227;o poucos os estudos que incluem idosos acima de 70 anos e os resultados s&#227;o, de modo geral, extrapolados de popula&#231;&#245;es mais jovens para as mais velhas, ignorando as particularidades destas.<xref ref-type="bibr" rid="B126"><sup>126</sup></xref></p>
        <p>A avalia&#231;&#227;o cl&#237;nica do idoso deve considerar os processos biol&#243;gicos subjacentes ao envelhecimento dito normativo, como a redu&#231;&#227;o fisiol&#243;gica das m&#250;ltiplas fun&#231;&#245;es org&#226;nicas que podem causar respostas inadequadas aos anest&#233;sicos, analg&#233;sicos e outras subst&#226;ncias administradas, bem como propiciar o aparecimento de complica&#231;&#245;es cardiovasculares, acidentes hemorr&#225;gicos, neuropsiqui&#225;tricos, entre outros. A avalia&#231;&#227;o de comorbidades associadas e suas repercuss&#245;es sobre a nutri&#231;&#227;o, funcionalidade geral, independ&#234;ncia e expectativa de vida &#250;til se faz obrigat&#243;ria, bem como de todos os medicamentos em uso, tanto para a preven&#231;&#227;o de poss&#237;veis complica&#231;&#245;es como para a escolha do procedimento mais adequado ao caso.<xref ref-type="bibr" rid="B127"><sup>127</sup></xref></p>
        <p>Como regra geral, o estabelecimento do risco cir&#250;rgico de um paciente deve ser individualizado e respeitado o preceito bio&#233;tico de autonomia do paciente em suas decis&#245;es ou do seu representante legal em caso de impossibilidade, ap&#243;s esclarecimento suficiente sobre os riscos inerentes &#224; doen&#231;a e ao procedimento cir&#250;rgico, durante os per&#237;odos intraoperat&#243;rio, p&#243;s-operat&#243;rio imediato e tardio, e &#224; qualidade de vida esperada com a realiza&#231;&#227;o do tratamento. Documentar no prontu&#225;rio a decis&#227;o do paciente e /ou representante legal.<xref ref-type="bibr" rid="B128"><sup>128</sup></xref></p>
        <p>Com estas considera&#231;&#245;es o risco cir&#250;rgico deve ser estabelecido sobre um trip&#233; constitu&#237;do por: (1) natureza e car&#225;ter da cirurgia; (2) capacidade funcional; (3) perfil de risco do paciente.</p>
        <p>As novas diretrizes t&#234;m estabelecido baixo risco para cirurgias eletivas e de pequeno porte, em que a possibilidade de ocorr&#234;ncia de infarto do mioc&#225;rdio ou de eventos adversos cardiovasculares maiores for &#8804;1%, e alto risco quando estas possibilidades forem &#8805; 1%. As publica&#231;&#245;es mais recentes t&#234;m incorporado o risco intermedi&#225;rio ao alto risco.<xref ref-type="bibr" rid="B129"><sup>129</sup></xref> Pacientes indicados para cirurgia de urg&#234;ncia devem ter seu risco estabelecido, sempre que poss&#237;vel, por informa&#231;&#245;es de familiares ou do pr&#243;prio paciente e ser encaminhados ao centro cir&#250;rgico. Em caso de cirurgias eletivas em que as condi&#231;&#245;es hemodin&#226;micas do paciente forem inst&#225;veis, este dever&#225; ser tratado at&#233; a estabiliza&#231;&#227;o do quadro e a escolha do momento mais oportuno para a realiza&#231;&#227;o da opera&#231;&#227;o.</p>
        <p>A capacidade funcional do paciente &#233; um valioso marcador de risco para complica&#231;&#245;es no transcurso da cirurgia e no per&#237;odo p&#243;s-operat&#243;rio. A possibilidade de subir dois andares por escadas, ou aclives ou caminhar no plano em velocidade aproximada de 4 mph corresponde a um equivalente metab&#243;lico (MET) &#8805; 4, o que nos indica uma boa reserva cardiovascular e capacidade f&#237;sica regular ou &#243;tima se for &#8805; 10 MET.</p>
        <p>O &#250;ltimo passo nesta estrat&#233;gia ser&#225; o de estabelecer o perfil de risco do paciente com base em sua hist&#243;ria cl&#237;nica, sintomas, sinais e dados laboratoriais. Na presen&#231;a de sintomas de s&#237;ndromes coronarianas inst&#225;veis, IC descompensada, doen&#231;a valvar sintom&#225;tica, arritmias graves ou embolia pulmonar que possam comprometer o transcurso do per&#237;odo peroperat&#243;rio, est&#227;o indicados exames n&#227;o invasivos para sua melhor compreens&#227;o. Quando os exames n&#227;o invasivos forem sugestivos de insufici&#234;ncia coron&#225;ria, estar&#227;o indicados exame de cintilografia de estresse e eventual coronariografia e mesmo a revasculariza&#231;&#227;o do mioc&#225;rdio, desde que a sua realiza&#231;&#227;o possa mudar substancialmente o manuseio do paciente ou sua sobrevida, levando em conta a gravidade de sua doen&#231;a de base.<xref ref-type="bibr" rid="B130"><sup>130</sup></xref></p>
      </sec>
      <sec>
        <title>1.14. Vacina&#231;&#227;o em Idosos</title>
        <sec>
          <title>1.14.1. Recomenda&#231;&#245;es da Sociedade Brasileira de Imuniza&#231;&#245;es (SBIm) &#8211; 2015/2016<xref ref-type="bibr" rid="B131"><sup>131</sup></xref></title>
          <p>Gripe ( <italic>Influenza</italic>) [indicada para todos os idosos] &#8211; A gripe &#233; uma infec&#231;&#227;o respirat&#243;ria aguda muito contagiosa, causada por um v&#237;rus que n&#227;o &#233; espec&#237;fico dos humanos (o v&#237;rus infecta v&#225;rios vertebrados dom&#233;sticos e selvagens que, por sua vez, contagiam os humanos), o <italic>Myxovirus influenzae</italic>, com tr&#234;s tipos conhecidos &#8211; A, B e C &#8211;, sem imunidade cruzada entre eles. O tipo A &#233; o mais virulento, causador das maiores epidemias, e subdivide-se ainda em subtipos, conforme as caracter&#237;sticas das suas mol&#233;culas superficiais (designadas abreviadamente por HA e NA). Nos humanos h&#225; presentemente em circula&#231;&#227;o dois subtipos de gripe A: o H1N1 e o H3N2.</p>
          <p>A mortalidade associada &#224; doen&#231;a pode ser elevada nos indiv&#237;duos mais idosos e nos muito jovens e em indiv&#237;duos com patologias respirat&#243;rias, cardiovasculares, renais ou diabetes, por exemplo. A gravidade da doen&#231;a pode ser devida ao pr&#243;prio v&#237;rus ou, mais frequentemente, a infec&#231;&#245;es bacterianas que se sobrep&#245;em na sequ&#234;ncia de uma gripe. H&#225; dois tipos de vacina contra a gripe, a trivalente (3V), e a tetravalente (4V). A trivalente protege contra as cepas H1N1, H3N2 (ambos <italic>influenza</italic> A) e, tamb&#233;m contra um tipo de v&#237;rus da <italic>influenza</italic> B. A tetravalente protege contra as mesmas cepas citadas e, ainda, contra um segundo v&#237;rus da influenza B. Desde que dispon&#237;vel, a vacina influenza 4V &#233; prefer&#237;vel &#224; vacina <italic>influenza</italic> 3V, por conferir maior cobertura das cepas circulantes. Na impossibilidade de uso da vacina 4V, utilizar a vacina 3V. A vacina ofertada na rede p&#250;blica &#233; a trivalente. Contraindica&#231;&#245;es. Hipersensibilidade sist&#234;mica conhecida a qualquer medicamento ou subst&#226;ncia, inclusive &#224; neomicina, ao formalde&#237;do, ao triton-X-100 (octoxinol 9), ao ovo ou &#224; prote&#237;na de galinha ou ap&#243;s a administra&#231;&#227;o desta vacina ou uma vacina contendo a mesma composi&#231;&#227;o. Pessoas com doen&#231;as febris agudas normalmente n&#227;o devem ser vacinadas at&#233; que os sintomas tenham desaparecido.</p>
          <p>Pneumoc&#243;cica [indicada para todos os idosos] &#8211; Evita Infec&#231;&#245;es invasivas (sepse, meningite, pneumonia e bacteriemia) e otite m&#233;dia aguda (OMA), causadas por alguns sorotipos do <italic>Streptococcus pneumoniae</italic>. Iniciar com uma dose da VPC13 seguida de uma dose de VPP23 seis a doze meses depois, e uma segunda dose de VPP23 cinco anos depois da primeira. Para aqueles que j&#225; receberam a VPP23, recomenda-se o intervalo de um ano para a aplica&#231;&#227;o de VPC13. A segunda dose de VPP23 deve ser feita cinco anos ap&#243;s a primeira, mantendo intervalo de seis a doze meses com a VPC13. Para os que j&#225; receberam duas doses de VPP23, recomenda-se uma dose de VPC13, com intervalo m&#237;nimo de um ano ap&#243;s a &#250;ltima dose de VPP23. Se a segunda dose de VPP23 foi aplicada antes dos 65 anos, est&#225; recomendada uma terceira dose depois dessa idade, com intervalo m&#237;nimo de cinco anos da &#250;ltima dose. Dispon&#237;vel na rede p&#250;blica para grupos de risco (DPOC, diabetes etc.)</p>
          <p>Tr&#237;plice bacteriana tipo adulto (dTpa)/Dupla bacteriana (dT) [indicada para todos os idosos] &#8211; Evita difteria, t&#233;tano e coqueluche (dTpa)/difteria e t&#233;tano (dT). Atualizar dTpa independentemente de intervalo pr&#233;vio com dT ou TT. Para idosos que pretendam viajar para pai&#769;ses nos quais a poliomielite seja ende&#770;mica, recomenda-se a vacina dTpa combinada a&#768; po&#769;lio inativada (dTpa-VIP). A dTpa-VIP pode substituir a dTpa. Com esquema de vacina&#231;&#227;o b&#225;sico para t&#233;tano completo: reforc&#807;o com dTpa a cada dez anos. Com esquema de vacina&#231;&#227;o b&#225;sico para t&#233;tano incompleto: uma dose de dTpa a qualquer momento e completar a vacinac&#807;a&#771;o ba&#769;sica com uma ou duas doses de dT (dupla bacteriana do tipo adulto) de forma a totalizar tre&#770;s doses de vacina contendo o componente teta&#770;nico. A vacina esta&#769; recomendada mesmo para aqueles que tiveram a coqueluche, ja&#769; que a protec&#807;a&#771;o conferida pela infecc&#807;a&#771;o na&#771;o e&#769; permanente. Considerar antecipar refor&#231;o com dTpa para cinco anos ap&#243;s a &#250;ltima dose de vacina contendo o componente pert&#250;ssis em idosos contactantes de lactentes. A dT est&#225; dispon&#237;vel na rede p&#250;blica.</p>
          <p>Herpes-z&#243;ster [indicada para todos os idosos] &#8211; Vacina recomendada mesmo para aqueles que j&#225; apresentaram quadro de herpes-z&#243;ster. Nesses casos, aguardar intervalo m&#237;nimo de um ano entre o quadro agudo e a aplica&#231;&#227;o da vacina. Em caso de pacientes com hist&#243;ria de herpes-z&#243;ster oft&#225;lmico, n&#227;o existem ainda dados suficientes para indicar ou contraindicar a vacina. Uso em imunodeprimidos: a vacina n&#227;o deve ser empregada em indiv&#237;duos com estado de imunodefici&#234;ncia prim&#225;ria ou adquirida ou em uso de terap&#234;uticas em posologias consideradas imunossupressoras. N&#227;o est&#225; dispon&#237;vel na rede p&#250;blica.</p>
        </sec>
        <sec>
          <title>1.14.2. Outras Vacinas (N&#227;o Rotineiras)</title>
          <p>Hepatite A, B ou A+B &#8211; Hepatite A: duas doses, no esquema 0-6 meses. Hepatite B: tr&#234;s doses, esquema 0-1-6 meses. Hepatite A e B: tr&#234;s doses, no esquema 0-1-6 meses. Para hepatite A: na popula&#231;&#227;o com mais de 60 anos de idade &#233; incomum encontrar indiv&#237;duos suscet&#237;veis. Para esse grupo, portanto, a vacina&#231;&#227;o n&#227;o e&#769; priorit&#225;ria. A sorologia pode ser solicitada para defini&#231;&#227;o da necessidade ou n&#227;o de vacinar. Em contactantes de doentes com hepatite A, ou durante surto da doen&#231;a, a vacina&#231;&#227;o deve ser considerada. Para hepatite A, B e A+B: a vacina combinada para as hepatites A e B &#233; uma op&#231;&#227;o e pode substituir a vacina&#231;&#227;o isolada para as hepatites A e B.</p>
          <p>Febre amarela &#8211; Uma dose em residentes em &#225;rea de risco ou viajantes a essas &#225;reas, vacinar pelo menos 10 dias antes da viagem. Ap&#243;s 10 anos, persistindo o risco, fazer uma segunda dose. A vacina &#233; contraindicada para imunodeprimidos; por&#233;m, quando os riscos de adquirir a doen&#231;a superarem os riscos potenciais da vacina&#231;&#227;o, o m&#233;dico deve avaliar sua utiliza&#231;&#227;o. H&#225; relatos de maior risco de eventos adversos graves nos maiores de 60 anos de idade; portanto, na primovacina&#231;&#227;o, avaliar risco/benefi&#769;cio.</p>
          <p>Tr&#237;plice viral (aarampo, caxumba e rub&#233;ola) &#8211; &#201; considerado protegido o indiv&#237;duo que tenha recebido, em algum momento da vida, duas doses da vacina tr&#237;plice viral acima de 1 ano de idade, e com intervalo m&#237;nimo de um m&#234;s entre elas. Est&#225; indicada em situa&#231;&#245;es de risco aumentado, j&#225; que a maioria das pessoas nessa faixa et&#225;ria n&#227;o &#233; suscet&#237;vel a essas doen&#231;as. Na popula&#231;&#227;o com mais de 60 anos de idade &#233; incomum encontrar indiv&#237;duos suscet&#237;veis a sarampo, caxumba e rub&#233;ola. Para esse grupo, portanto, a vacina&#231;&#227;o n&#227;o &#233; rotineira. Por&#233;m, a crit&#233;rio m&#233;dico (em situa&#231;&#245;es de surtos, viagens, entre outros), pode ser recomendada. Contraindicada para imunodeprimidos.</p>
          <p>Recomenda&#231;&#227;o: Sempre que poss&#237;vel, preferir vacinas combinadas e aplica&#231;&#245;es simult&#226;neas na mesma visita.</p>
        </sec>
      </sec>
      <sec>
        <title>1.15. Cuidados Paliativos</title>
        <p>Os cuidados paliativos (CP), inicialmente voltados para a oncologia, v&#234;m sendo incorporados em diversas &#225;reas de atua&#231;&#227;o. A cardiologia &#233; uma delas, com a discuss&#227;o dos CP no &#226;mbito das DCV, especialmente envolvendo a popula&#231;&#227;o mais idosa, da&#237; o assunto merecer uma abordagem neste documento.</p>
        <p>De acordo com a OMS os CP s&#227;o definidos como um modelo de assist&#234;ncia promovida por uma equipe multidisciplinar, objetivando a melhoria de qualidade de vida do paciente e seus familiares, frente a uma doen&#231;a que ameace a continuidade da vida, por meio de preven&#231;&#227;o e al&#237;vio de sofrimento.<xref ref-type="bibr" rid="B132"><sup>132</sup></xref> Os CP requerem identifica&#231;&#227;o precoce, avalia&#231;&#227;o e tratamento da dor e demais problemas f&#237;sicos, sociais, psicol&#243;gicos e espirituais.<xref ref-type="bibr" rid="B132"><sup>132</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B133"><sup>133</sup></xref></p>
        <p>Os CP devem ser individualizados; n&#227;o se trata da abordagem de pacientes &#8220;terminais&#8221;, e sim de uma condi&#231;&#227;o cl&#237;nica que ameace a vida.<xref ref-type="bibr" rid="B133"><sup>133</sup></xref> Sua indica&#231;&#227;o deve ser precoce, no momento do diagn&#243;stico, de modo a favorecer o entendimento, a aceita&#231;&#227;o e a expans&#227;o progressiva das medidas de suporte ao longo do tempo. Deve-se discutir a possibilidade ou n&#227;o de tratamentos que modifiquem a doen&#231;a, de forma que n&#227;o existe a ideia de &#8220;n&#227;o h&#225; nada a fazer&#8221;.<xref ref-type="bibr" rid="B133"><sup>133</sup></xref></p>
        <p>Os princ&#237;pios que regem os CP de acordo com a OMS consistem em:<xref ref-type="bibr" rid="B132"><sup>132</sup></xref></p>
        <list list-type="order">
          <list-item>
            <p>Promover al&#237;vio da dor e outros sintomas desagrad&#225;veis.</p>
          </list-item>
          <list-item>
            <p>Afirmar a vida e considerar a morte como um processo normal da vida.</p>
          </list-item>
          <list-item>
            <p>N&#227;o acelerar nem adiar a morte.</p>
          </list-item>
          <list-item>
            <p>Integrar aspectos psicol&#243;gicos e espirituais no cuidado ao paciente.</p>
          </list-item>
          <list-item>
            <p>Oferecer um sistema de suporte que possibilite ao paciente viver t&#227;o ativamente quanto poss&#237;vel, at&#233; o momento da morte.</p>
          </list-item>
          <list-item>
            <p>Oferecer sistema de suporte que auxilie aos familiares enfrentar a doen&#231;a do paciente e o luto.</p>
          </list-item>
          <list-item>
            <p>Melhorar a qualidade de vida e influenciar positivamente o curso da doen&#231;a.</p>
          </list-item>
          <list-item>
            <p>Iniciar estes cuidados o mais precocemente poss&#237;vel, juntamente com outras medidas de prolongamento da vida, como quimioterapia e radioterapia, e incluir todas as investiga&#231;&#245;es necess&#225;rias para melhor compreender e controlar situa&#231;&#245;es cl&#237;nicas existentes.</p>
          </list-item>
        </list>
        <p>Do ponto de vista te&#243;rico, todos os pacientes portadores de doen&#231;as graves, incur&#225;veis e progressivas, que ameacem a continuidade da vida, deveriam receber CP.<xref ref-type="bibr" rid="B133"><sup>133</sup></xref> Se esta refer&#234;ncia fosse assumida, o n&#250;mero de pacientes com indica&#231;&#227;o de CP seria enorme e n&#227;o haveria como prestar este tipo de assist&#234;ncia a todos. Por este motivo, a Academia Nacional de Cuidados Paliativos (ANCP)<xref ref-type="bibr" rid="B133"><sup>133</sup></xref> recomenda a ado&#231;&#227;o dos crit&#233;rios utilizados no Medicare americano,<xref ref-type="bibr" rid="B134"><sup>134</sup></xref> que estabelece o tempo de sobrevida esperado como um dos crit&#233;rios para a indica&#231;&#227;o dos CP. Adaptando os crit&#233;rios do Medicare, podemos sugerir as seguintes condi&#231;&#245;es para a indica&#231;&#227;o dos CP:<xref ref-type="bibr" rid="B133"><sup>133</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B134"><sup>134</sup></xref></p>
        <list list-type="order">
          <list-item>
            <p>Paciente com expectativa de vida menor ou igual a 6 meses.</p>
          </list-item>
          <list-item>
            <p>Diagn&#243;stico de uma doen&#231;a incur&#225;vel e irrevers&#237;vel.</p>
          </list-item>
          <list-item>
            <p>O paciente deve fazer a op&#231;&#227;o pelos CP, abrindo m&#227;o dos tratamentos de prolongamento de vida.</p>
          </list-item>
          <list-item>
            <p>Deve haver disponibilidade operacional para a implementa&#231;&#227;o dos CP.</p>
          </list-item>
        </list>
        <p>A avalia&#231;&#227;o progn&#243;stica de paciente em CP &#233; um processo complexo que envolve julgamentos fisiol&#243;gicos e sociais. A ANCP sugere alguns instrumentos para avalia&#231;&#227;o da funcionalidade do paciente, bem como a aferi&#231;&#227;o de decl&#237;nios funcionais e cl&#237;nicos, como a escala de <italic>performance</italic> status de Karnofsky e a escala de <italic>Performance</italic> Paliativa. Estas escalas e seus m&#233;todos de avalia&#231;&#227;o est&#227;o detalhados no Manual de Cuidados Paliativos da ANCP, dispon&#237;vel na biblioteca virtual (<ext-link ext-link-type="uri" xlink:href="http://paliativo.org.br/">http://paliativo.org.br/</ext-link>).<xref ref-type="bibr" rid="B133"><sup>133</sup></xref></p>
        <p>Em rela&#231;&#227;o &#224;s DCV, sabemos que s&#227;o a principal causa de morte no Brasil, bem como em diversas partes do mundo. Podem ocorrer em qualquer idade, mas t&#234;m preval&#234;ncia maior com o envelhecimento.<xref ref-type="bibr" rid="B133"><sup>133</sup></xref> Dentre as DCV, a IC representa um desafio na avalia&#231;&#227;o progn&#243;stica, uma vez que muitos pacientes morrem subitamente, mesmo em classes funcionais iniciais. Diversos crit&#233;rios t&#234;m procurado identificar pacientes com IC em risco de morte s&#250;bita, como: fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo (FEVE), pept&#237;dio natriur&#233;tico do tipo B, di&#226;metro diast&#243;lico final do VE, presen&#231;a de taquicardia ventricular n&#227;o sustentada, diabetes melito, fen&#244;menos tromboemb&#243;licos, hist&#243;ria de parada cardiorrespirat&#243;ria pr&#233;via e diagn&#243;stico de AIDS.<xref ref-type="bibr" rid="B133"><sup>133</sup></xref> A dificuldade de prognosticar os pacientes com IC torna a discuss&#227;o com o paciente sobre suas prefer&#234;ncias de cuidados dif&#237;cil e, por este motivo, esses pacientes t&#234;m sido considerados os com menor compreens&#227;o de sua condi&#231;&#227;o cl&#237;nica e pouco envolvimento no processo decis&#243;rio em rela&#231;&#227;o a seus cuidados.<xref ref-type="bibr" rid="B133"><sup>133</sup></xref> Os pacientes com DCV apresentam grande sofrimento e est&#227;o entre os que menos recebem assist&#234;ncia domiciliar e CP; por este motivo, esta Diretriz concorda que os CP devam ser considerados mais precocemente no decurso evolutivo das DCV e a pr&#225;tica inclu&#237;da na rotina da cardiologia.</p>
      </sec>
    </sec>
    <sec>
      <title>2. Coronariopatia Cr&#244;nica</title>
      <sec>
        <title>2.1. Peculiaridades do Diagn&#243;stico da Doen&#231;a Arterial Coronariana Cr&#244;nica no Idoso</title>
        <p>Hist&#243;ria cl&#237;nica e exame f&#237;sico detalhados s&#227;o essenciais na avalia&#231;&#227;o do idoso com suspeita de DAC cr&#244;nica; todavia, na pr&#225;tica cotidiana isto constitui um desafio, face &#224; ocorr&#234;ncia de comorbidades, sintomas at&#237;picos e altera&#231;&#245;es cognitivas e de locomo&#231;&#227;o. A apresenta&#231;&#227;o de isquemia frequentemente acontece sob forma de equivalentes anginosos: fadiga, dispneia, desconforto epig&#225;strico, sendo incomum a presen&#231;a de angina t&#237;pica.<xref ref-type="bibr" rid="B135"><sup>135</sup></xref> O exame f&#237;sico, geralmente inespec&#237;fico, pode fornecer algumas pistas, tais como: HAS, anormalidades de ritmo (fibrila&#231;&#227;o atrial &#8211; FA) e doen&#231;a arterial perif&#233;rica.</p>
        <p>O ECG de repouso pode ser inespec&#237;fico em 50% dos casos, mesmo na vig&#234;ncia de coronariopatia grave;<xref ref-type="bibr" rid="B136"><sup>136</sup></xref> no idoso s&#227;o frequentes altera&#231;&#245;es como ondas Q patol&#243;gicas, invers&#245;es da onda T, hipertrofia ventricular esquerda (HVE), bloqueios de ramo do feixe de His, FA. Tais altera&#231;&#245;es dificultam o diagn&#243;stico. O ECG &#233; particularmente &#250;til, durante epis&#243;dios de angina, quando pode ser constatada depress&#227;o do segmento ST ou pseudonormaliza&#231;&#227;o do mesmo, em at&#233; 50% dos casos.</p>
        <p>A radiografia de t&#243;rax deve ser realizada quando coexistir suspeita de IC congestiva, valvopatia ou doen&#231;a pulmonar.</p>
        <p>O ecocardiograma transtor&#225;cico fornece informa&#231;&#245;es relevantes para o diagn&#243;stico e manuseio da DAC cr&#244;nica: (a) estado do VE &#8211; fun&#231;&#245;es sist&#243;lica e diast&#243;lica, mobilidade parietal e hipertrofia; (b) presen&#231;a de valvopatias; (c) situa&#231;&#227;o da raiz da aorta.</p>
        <p>A utiliza&#231;&#227;o de testes funcionais para isquemia [TE, ecocardiografia sob estresse e cintilografia mioc&#225;rdica de perfus&#227;o (CMP)] ou de testes anat&#244;micos [angiotomografia de coron&#225;rias (ATC) e cineangiocoronariografia (CATE)] depende da estimativa pr&#233;-teste da probabilidade de DAC obstrutiva.<xref ref-type="bibr" rid="B137"><sup>137</sup></xref> Quando a probabilidade for baixa (&lt; 20%), &#233; desnecess&#225;rio prosseguir na investiga&#231;&#227;o. Por outro lado, quando a probabilidade for alta (&gt; 80%), resultados negativos de exames n&#227;o invasivos podem n&#227;o excluir DAC obstrutiva e, portanto, a estrat&#233;gia invasiva pode ser considerada. Para aqueles com probabilidade pr&#233;-teste intermedi&#225;ria estaria indicado um exame de estresse.</p>
        <p>No idoso, a sensibilidade e a especificidade diagn&#243;stica do TE t&#234;m sido questionadas,<xref ref-type="bibr" rid="B138"><sup>138</sup></xref> em decorr&#234;ncia da baixa capacidade de exerc&#237;cio (redu&#231;&#227;o de massa muscular, descondicionamento, comorbidades) e da presen&#231;a de altera&#231;&#245;es no ECG de base; todavia, esta metodologia pode ser &#250;til no manuseio cl&#237;nico, oferecendo informa&#231;&#245;es relevantes sobre sintomas, capacidade de exerc&#237;cio, resposta cronotr&#243;pica, arritmias etc.</p>
        <p>Tanto a estresse como a CMP podem ser utilizadas associadas ao TE para incrementar a sensibilidade e a especificidade para isquemia.<xref ref-type="bibr" rid="B139"><sup>139</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B140"><sup>140</sup></xref> A utilidade diagn&#243;stica e progn&#243;stica de ambas as modalidades &#233; similar e a prefer&#234;ncia por uma determinada metodologia depende de experi&#234;ncia e/ou equipamentos dispon&#237;veis em cada centro de investiga&#231;&#227;o. Para os gerontes incapazes de realizar exerc&#237;cio, podem ser utilizados estresse farmacol&#243;gico tanto na estresse (dobutamina) como na CMP (agentes vasodilatadores).</p>
        <p>O ECC, obtido conjuntamente com a ATC, &#233; &#250;til na estratifica&#231;&#227;o de risco de idosos assintom&#225;ticos, pelo seu alto valor preditivo negativo;<xref ref-type="bibr" rid="B141"><sup>141</sup></xref> todavia, naqueles sintom&#225;ticos, com suspeita de DAC, seu valor &#233; limitado. Devido &#224; alta preval&#234;ncia de calcifica&#231;&#227;o de coron&#225;rias em gerontes, a ATC tem se mostrado com acur&#225;cia reduzida na demonstra&#231;&#227;o de DAC obstrutiva.<xref ref-type="bibr" rid="B142"><sup>142</sup></xref></p>
        <p>O CATE continua sendo o &#8220;padr&#227;o-ouro&#8221; para a avalia&#231;&#227;o definitiva de DAC epic&#225;rdica; geralmente &#233; recomendado para pacientes cujas caracter&#237;sticas cl&#237;nicas e/ou resultados de testes n&#227;o invasivos indiquem uma alta probabilidade de coronariopatia grave, com alto risco de eventos coronarianos ou morte. Apesar de bem tolerado, merece aten&#231;&#227;o pelo risco de sangramento, AVE, nefropatia por contraste.</p>
      </sec>
      <sec>
        <title>2.2. Peculiaridades do Tratamento da Doen&#231;a Arterial Coronariana Cr&#244;nica no Idoso</title>
        <p>Nas &#250;ltimas d&#233;cadas o tratamento da doen&#231;a coronariana tem sido bem fundamentado em torno de medidas cl&#237;nicas gerais relacionadas ao desenvolvimento de h&#225;bitos saud&#225;veis, tais como: alimenta&#231;&#227;o balanceada, controle do peso, pr&#225;tica regular de atividade f&#237;sica, cumprimento de programa&#231;&#227;o vacinal, aboli&#231;&#227;o do tabagismo, controle rigoroso da PA e uso apropriado de medicamentos antiateroscler&#243;ticos como estatina, antiplaquet&#225;rio e atenuadores do sistema renina-angiotensina, al&#233;m de antianginosos.<xref ref-type="bibr" rid="B143"><sup>143</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B145"><sup>145</sup></xref> Adicionalmente, em casos bem selecionados, com procedimentos de revasculariza&#231;&#227;o mioc&#225;rdica, por meio de interven&#231;&#227;o coronariana percut&#226;nea ou por cirurgia. Nos pacientes idosos esses princ&#237;pios gerais s&#227;o aplic&#225;veis em boa parte com evid&#234;ncias poss&#237;veis de serem extra&#237;das de estudos randomizados, que passaram a incluir em suas observa&#231;&#245;es indiv&#237;duos idosos &#8220;jovens&#8221; &#8211; 60 a 75 anos de idade &#8211;, sendo que estas s&#227;o menos avaliadas nos &#8220;idosos propriamente ditos&#8221; &#8211; 75 a 85 anos de idade &#8211;, e escassas nos &#8220;muito idosos&#8221; &#8211; mais de 85 anos.<xref ref-type="bibr" rid="B143"><sup>143</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B145"><sup>145</sup></xref></p>
        <p>Em rela&#231;&#227;o &#224; dieta, os estudos Lyon, <italic>Dietary Approaches to Stop Hypertension</italic> (DASH) e, mais recentemente, o <italic>Prevenci&#243;n con Dieta Mediterr&#225;nea</italic> (PREDIMED) validam o conceito da dieta saud&#225;vel e este &#250;ltimo incluiu pacientes de at&#233; 80 anos de idade. O controle do peso oferece uma considera&#231;&#227;o particular no idoso pela aparente constata&#231;&#227;o do paradoxo do IMC com a idade.<xref ref-type="bibr" rid="B146"><sup>146</sup></xref> Em uma an&#225;lise mais conclusiva do assunto em DAC, a redu&#231;&#227;o da obesidade se associa a melhores resultados.</p>
        <p>A pr&#225;tica regular de atividades apropriadas para as condi&#231;&#245;es f&#237;sicas do idoso trazem incont&#225;veis benef&#237;cios de ordem psicol&#243;gica que impactam na melhoria dos cuidados gerais de sa&#250;de, e que justificam sua implementa&#231;&#227;o.</p>
        <p>Inflama&#231;&#227;o determinada por infec&#231;&#245;es desempenha um reconhecido papel no surgimento de complica&#231;&#245;es em doen&#231;a coronariana, e vacina&#231;&#227;o contra <italic>influenza</italic> e pneumococos &#233; medida recomend&#225;vel no idoso coronariopata.<xref ref-type="bibr" rid="B147"><sup>147</sup></xref></p>
        <p>A an&#225;lise do registro <italic>Coronary Artery Study</italic> (CASS) foi definitivo em demonstrar o benef&#237;cio de abolir o tabagismo no coronariopata idoso.<xref ref-type="bibr" rid="B148"><sup>148</sup></xref></p>
        <p>No idoso tem-se estabelecida meta de controle de press&#227;o arterial sist&#243;lica (PAS) &lt; 140 mmHg. Recente estudo (<italic>Systolic Blood Pressure Intervention Trial</italic> &#8211; SPRINT) recomenda que mesmo no idoso com doen&#231;a coronariana esta meta seja mais rigorosa (se tolerada, &lt; 130 mmHg), n&#227;o tendo sido verificada a curva J nem eventos indesej&#225;veis relacionados &#224; redu&#231;&#227;o da PA diast&#243;lica. Cautela especial dever&#225; ser tida nesta popula&#231;&#227;o com comorbidades.<xref ref-type="bibr" rid="B149"><sup>149</sup></xref></p>
        <p>As medica&#231;&#245;es antiateroscler&#243;ticas como as estatinas t&#234;m demonstra&#231;&#227;o confirmada, em ensaios, at&#233; os 79 anos de idade. Se toleradas devem ser estimuladas a atingir metas de LDL-c de &lt; 70 mg/dL. O &#225;cido acetilsalic&#237;lico (AAS) &#233; recomendado, assim como o emprego de inibidores da enzima conversora de angiotensina (IECA) ou bloqueadores dos receptores de angiotensina (BRA), mesmo na aus&#234;ncia de HAS ou IC, embora ambas estas condi&#231;&#245;es frequentemente estejam associadas a DAC no idoso.</p>
        <p>As medica&#231;&#245;es anti-isqu&#234;micas como betabloqueadores (e antagonistas de c&#225;lcio na sua impossibilidade ou em associa&#231;&#227;o) para controle e nitrato para as crises, assim como novos medicamentos anti-isqu&#234;micos, como trimetazidina, devem ser usados, com a devida cautela de doses progressivas, por conta da maior incid&#234;ncia de efeitos colaterais. Ivabradina pode ser considerada para controle da FC na impossibilidade de uso do betabloqueador.<xref ref-type="bibr" rid="B150"><sup>150</sup></xref></p>
        <p>Em rela&#231;&#227;o &#224; revasculariza&#231;&#227;o, tanto por interven&#231;&#227;o percut&#226;nea como cir&#250;rgica, no idoso sem fragilidade, deve ser considerada com vistas a controlar sintomas refrat&#225;rios ou em condi&#231;&#245;es de grande carga isqu&#234;mica. Quanto &#224; decis&#227;o de qual procedimento a ser realizado, interven&#231;&#227;o percut&#226;nea ou cirurgia, tudo depende da factibilidade de emprego das duas t&#233;cnicas, tendo a se considerar que a idade acrescenta um peso consider&#225;vel ao risco de ambos os procedimentos e os escores que incluem comorbidades associadas tendem a afetar ainda mais o procedimento cir&#250;rgico.<xref ref-type="bibr" rid="B151"><sup>151</sup></xref></p>
        <p>Por fim, as recomenda&#231;&#245;es terap&#234;uticas devem levar em conta, al&#233;m dos fatos mencionados anteriormente, outros tantos relevantes como aspectos biol&#243;gicos de fragilidade, compet&#234;ncia psicol&#243;gica, suporte econ&#244;mico, social, entre outros, que tornam a sua escolha um exemplo m&#225;ximo de terap&#234;utica personalizada voltada para o indiv&#237;duo idoso afetado por DAC.</p>
      </sec>
      <sec>
        <title>2.3. Recomenda&#231;&#245;es Gerais &#8211; Doen&#231;a Arterial Coronariana Cr&#244;nica no Idoso</title>
        <table-wrap id="t13">
          <table frame="hsides" rules="groups">
            <colgroup width="50%">
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr>
                <th align="left" valign="top" colspan="2">Tratamento da doen&#231;a coronariana cr&#244;nica no idoso</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top" rowspan="6">Medidas gerais</td>
                <td align="left" valign="top">&#9679; Alimenta&#231;&#227;o balanceada</td>
              </tr>
              <tr>
                <td align="left" valign="top">&#9679; Controle do peso</td>
              </tr>
              <tr>
                <td align="left" valign="top">Pr&#225;tica regular de atividade f&#237;sica</td>
              </tr>
              <tr>
                <td align="left" valign="top">&#9679; Cumprimento de programa&#231;&#227;o vacinal</td>
              </tr>
              <tr>
                <td align="left" valign="top">&#9679; Aboli&#231;&#227;o do tabagismo</td>
              </tr>
              <tr>
                <td align="left" valign="top">Controle rigoroso da press&#227;o arterial</td>
              </tr>
              <tr>
                <td align="left" valign="top" rowspan="3">Medicamentos antiateroscler&#243;ticos</td>
                <td align="left" valign="top">&#9679; Estatina</td>
              </tr>
              <tr>
                <td align="left" valign="top">&#9679; Antiplaquet&#225;rio</td>
              </tr>
              <tr>
                <td align="left" valign="top">&#9679; Atenuadores do sistema renina-angiotensina (IECA/BRA)</td>
              </tr>
              <tr>
                <td align="left" valign="top" rowspan="4">Medicamentos antianginosos</td>
                <td align="left" valign="top">&#9679; Betabloqueadores</td>
              </tr>
              <tr>
                <td align="left" valign="top">&#9679; Antagonistas do c&#225;lcio</td>
              </tr>
              <tr>
                <td align="left" valign="top">&#9679; Nitratos</td>
              </tr>
              <tr>
                <td align="left" valign="top">&#9679; Trimetazidina</td>
              </tr>
              <tr>
                <td align="left" valign="top" rowspan="2">Revasculariza&#231;&#227;o mioc&#225;rdica</td>
                <td align="left" valign="top">&#9679; Interven&#231;&#227;o coronariana percut&#226;nea</td>
              </tr>
              <tr>
                <td align="left" valign="top">&#9679; Cirurgia de revasculariza&#231;&#227;o mioc&#225;rdica</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN2a">
              <p><italic>BRA: bloqueador do receptor de angiotensina; IECA: inibidor da enzima conversora da angiotensina</italic>.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <table-wrap id="t14">
          <table frame="hsides" rules="groups">
            <colgroup width="33%">
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr>
                <th align="left" valign="top" colspan="3">Indica&#231;&#227;o de revasculariza&#231;&#227;o nos idosos assintom&#225;ticos</th>
              </tr>
              <tr>
                <th align="left" valign="top">Acentuada carga isqu&#234;mica</th>
                <th align="center" valign="top">Grau de Recomenda&#231;&#227;o</th>
                <th align="center" valign="top">N&#237;vel de Evid&#234;ncia</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top">Interven&#231;&#227;o percut&#226;nea</td>
                <td align="center" valign="top">IIa</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">Cirurgia</td>
                <td align="center" valign="top">IIa</td>
                <td align="center" valign="top">C</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <table-wrap id="t15">
          <table frame="hsides" rules="groups">
            <colgroup width="20%">
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr>
                <th align="left" valign="top" colspan="5">Avalia&#231;&#227;o diagn&#243;stica de coronariopatia cr&#244;nica no idoso</th>
              </tr>
              <tr>
                <th align="left" valign="top">M&#233;todo</th>
                <th align="center" valign="top">Aspectos positivos</th>
                <th align="center" valign="top">Poss&#237;veis limita&#231;&#245;es</th>
                <th align="center" valign="top">Grau de recomenda&#231;&#227;o</th>
                <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top">ECG</td>
                <td align="center" valign="top">F&#225;cil obten&#231;&#227;o. Detec&#231;&#227;o de zonas inativas, dist&#250;rbios de condu&#231;&#227;o</td>
                <td align="center" valign="top">Pouca acur&#225;cia</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Teste ergom&#233;trico</td>
                <td align="center" valign="top">Disponibilidade. Acur&#225;cia moderada na detec&#231;&#227;o de isquemia</td>
                <td align="center" valign="top">Dificuldades locomotoras Altera&#231;&#245;es electrocardiogr&#225;ficas no ECG de repouso</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Eco de estresse (dobutamina, esfor&#231;o ou dipiridamol)</td>
                <td align="center" valign="top">Detec&#231;&#227;o e avalia&#231;&#227;o da extens&#227;o da isquemia. Avalia&#231;&#227;o de fun&#231;&#227;o de VE</td>
                <td align="center" valign="top">Janela ecocardiogr&#225;fica. Custo</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Cintilografia</td>
                <td align="center" valign="top">Detec&#231;&#227;o e avalia&#231;&#227;o da extens&#227;o da isquemia. Independe de altera&#231;&#245;es eletrocardiogr&#225;ficas preexistentes. Avalia&#231;&#227;o de fun&#231;&#227;o de VE</td>
                <td align="center" valign="top">Menor disponibilidade. Custo</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Angiotomografia de coron&#225;rias</td>
                <td align="center" valign="top">Detec&#231;&#227;o de obstru&#231;&#245;es</td>
                <td align="center" valign="top">Calcifica&#231;&#227;o no idoso diminui acur&#225;cia do diagn&#243;stico</td>
                <td align="center" valign="top">IIa</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Angiorresson&#226;ncia magn&#233;tica de coron&#225;rias</td>
                <td align="center" valign="top">Detec&#231;&#227;o de obstru&#231;&#245;es</td>
                <td align="center" valign="top">Menor Acur&#225;cia. Dificuldades de obten&#231;&#227;o</td>
                <td align="center" valign="top">IIb</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">Resson&#226;ncia magn&#233;tica card&#237;aca</td>
                <td align="center" valign="top">Fun&#231;&#227;o de VE &#193;reas de fibrose</td>
                <td align="center" valign="top">Dificuldades de obten&#231;&#227;o</td>
                <td align="center" valign="top">IIb</td>
                <td align="center" valign="top">C</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN3a">
              <p><italic>ECG: eletrocardiograma; VE: ventr&#237;culo esquerdo</italic>.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <table-wrap id="t16">
          <table frame="hsides" rules="groups">
            <colgroup width="33%">
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr>
                <th align="left" valign="top" colspan="3">Recomenda&#231;&#245;es para medidas gerais e uso de antiateroscler&#243;ticos</th>
              </tr>
              <tr>
                <th align="left" valign="top">Procedimento/medicamento</th>
                <th align="center" valign="top">Grau de recomenda&#231;&#227;o</th>
                <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top">Alimenta&#231;&#227;o balanceada</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">A</td>
              </tr>
              <tr>
                <td align="left" valign="top">Controle de peso</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Atividade f&#237;sica</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Vacina&#231;&#227;o contra influenza</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Aboli&#231;&#227;o do tabagismo</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">A</td>
              </tr>
              <tr>
                <td align="left" valign="top">Controle da PA &lt; 140 mmHg</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">A</td>
              </tr>
              <tr>
                <td align="left" valign="top">Controle da PA &lt; 120 mmHg</td>
                <td align="center" valign="top">IIa</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Estatinas</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">A</td>
              </tr>
              <tr>
                <td align="left" valign="top">Antiplaquet&#225;rio</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">A</td>
              </tr>
              <tr>
                <td align="left" valign="top">IECA/BRA</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">A</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN4a">
              <p>
                <italic>BRA: bloqueador do receptor de angiotensina; IECA: inibidor da enzima conversora da angiotensina; PA: press&#227;o arterial.</italic>
              </p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <table-wrap id="t17">
          <table frame="hsides" rules="groups">
            <colgroup width="33%">
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr>
                <th align="left" valign="top" colspan="3">Recomenda&#231;&#245;es para antianginosos</th>
              </tr>
              <tr>
                <th align="left" valign="top">Medicamento</th>
                <th align="center" valign="top">Grau de recomenda&#231;&#227;o</th>
                <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top">Betabloqueador</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">A</td>
              </tr>
              <tr>
                <td align="left" valign="top">Antagonista de c&#225;lcio</td>
                <td align="center" valign="top">IIa</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Nitrato para crises anginosas</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">A</td>
              </tr>
              <tr>
                <td align="left" valign="top">Nitrato para uso cr&#244;nico</td>
                <td align="center" valign="top">IIb</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Trimetazidina</td>
                <td align="center" valign="top">IIa</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Ivabradina</td>
                <td align="center" valign="top">IIa</td>
                <td align="center" valign="top">B</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <table-wrap id="t18">
          <table frame="hsides" rules="groups">
            <colgroup width="33%">
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr>
                <th align="left" valign="top" colspan="3">Indica&#231;&#227;o de revasculariza&#231;&#227;o nos idosos anginosos refrat&#225;rios ao tratamento cl&#237;nico</th>
              </tr>
              <tr>
                <th align="left" valign="top">IPC - Pacientes com angina</th>
                <th align="center" valign="top">Grau de recomenda&#231;&#227;o</th>
                <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top">IPC fact&#237;vel de f&#225;cil aplica&#231;&#227;o</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">Escore Syntax baixo</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Escore Syntax elevado</td>
                <td align="center" valign="top">IIb</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">
                  <bold>Cirurgia &#8211; Pacientes com angina</bold>
                </td>
                <td align="center" valign="top">
                  <bold>Grau de recomenda&#231;&#227;o</bold>
                </td>
                <td align="center" valign="top">
                  <bold>N&#237;vel de evid&#234;ncia</bold>
                </td>
              </tr>
              <tr>
                <td align="left" valign="top">Multivascular de baixo risco cir&#250;rgico</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Escore Syntax baixo a moderado e alto risco cir&#250;rgico</td>
                <td align="center" valign="top">IIb</td>
                <td align="center" valign="top">B</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN5a">
              <p><italic>IPC: interven&#231;&#227;o percut&#226;nea; Syntax: Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery</italic>.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
    </sec>
    <sec>
      <title>3. Coronariopatia Aguda</title>
      <sec>
        <title>3.1. Peculiaridades no Diagn&#243;stico</title>
        <p>Idosos apresentam maior incid&#234;ncia de s&#237;ndrome coronariana aguda (SCA) e apresentam pior progn&#243;stico quando comparados aos mais jovens. Dentre as causas desta evolu&#231;&#227;o desfavor&#225;vel est&#227;o: (a) atraso na chegada ao hospital; (b) dificuldade diagn&#243;stica; (c) menor probabilidade de receber tratamento intervencionista; (d) menor uso de betabloqueadores; (e) IC pr&#233;via; (f) comorbidades.<xref ref-type="bibr" rid="B152"><sup>152</sup></xref> &#192; propor&#231;&#227;o que aumenta a idade, diminui a a&#231;&#227;o dos fatores de risco como hipertens&#227;o, diabetes e tabagismo e aumenta a import&#226;ncia das comorbidades associadas como o AVE, insufici&#234;ncias renal e card&#237;aca.<xref ref-type="bibr" rid="B153"><sup>153</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B154"><sup>154</sup></xref> A apresenta&#231;&#227;o at&#237;pica &#233; mais comum nesta faixa et&#225;ria: dor tor&#225;cica em 40% daqueles &#8805; 80 anos quando comparados a 80% nos &#8804; 65 anos de idade. Naqueles idosos com infarto, 8,4% apresentam-se sem dor precordial (43,3% nos &#8805; 75 anos comparados a 29,4% dos &#8804; 65 anos de idade). Sintomas mais comuns s&#227;o: dispneia (29,4%), sudorese (26,2%), n&#225;useas e v&#244;mitos (24,3%), s&#237;ncope e pr&#233;-s&#237;ncope (19,1%), denominados equivalentes isqu&#234;micos.</p>
        <p>Embora o exame f&#237;sico possa ser normal, a presen&#231;a ou aus&#234;ncia de sinais de hipoperfus&#227;o perif&#233;rica, sinais vitais, presen&#231;a ou aus&#234;ncia de pulsos arteriais, distens&#227;o venosa jugular, ausculta card&#237;aca (sopros, atritos, terceira bulha) e ausculta pulmonar com sinais de congest&#227;o s&#227;o dados importantes a serem avaliados. ECG inicial &#233; menos solicitado, al&#233;m de mais tardio nos idosos: 40% dos &#8805; 85 anos comparados a 25% dos &#8804; 65 anos de idade n&#227;o t&#234;m ECG diagn&#243;stico. A presen&#231;a de altera&#231;&#245;es eletrocardiogr&#225;ficas inespec&#237;ficas e bloqueios &#233; mais frequente nos idosos, aumentando as dificuldades diagn&#243;sticas nesta faixa et&#225;ria, especialmente a presen&#231;a de bloqueio de ramo esquerdo.<xref ref-type="bibr" rid="B102"><sup>102</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B155"><sup>155</sup></xref> Eleva&#231;&#245;es de marcadores de necrose mioc&#225;rdica n&#227;o relacionadas &#224; SCA s&#227;o comuns em outras situa&#231;&#245;es: aumento dos n&#237;veis plasm&#225;ticos da por&#231;&#227;o N-terminal do pr&#243;-pept&#237;dio natriur&#233;tico cerebral (NT-pr&#243;-BNP), diabetes, insufici&#234;ncia renal, anemia, desidrata&#231;&#227;o, dist&#250;rbios metab&#243;licos e hidreletrol&#237;ticos, infec&#231;&#245;es e anormalidades ecocardiogr&#225;ficas em cardiopatias cr&#244;nicas.<xref ref-type="bibr" rid="B156"><sup>156</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B159"><sup>159</sup></xref></p>
        <p>Os escores de risco, como o <italic>Thrombolysis in Myocardial Infarction</italic> (TIMI) Risk<xref ref-type="bibr" rid="B160"><sup>160</sup></xref> e o <italic>Global Registry of Acute Coronary Events</italic> (GRACE),<xref ref-type="bibr" rid="B161"><sup>161</sup></xref> s&#227;o importantes na estratifica&#231;&#227;o de risco dos idosos com SCA, garantindo melhor estrat&#233;gia na abordagem diagn&#243;stica e terap&#234;utica, aumentando o uso de antitromb&#243;ticos, anticoagula&#231;&#227;o e revasculariza&#231;&#227;o mioc&#225;rdica com consequente redu&#231;&#227;o do risco de morte, infarto e isquemia recorrente.<xref ref-type="bibr" rid="B162"><sup>162</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B163"><sup>163</sup></xref> Ter mais de 70 anos de idade confere um risco moderado (70 a 75 anos) a alto (&gt; 75 anos) para doen&#231;a coronariana.</p>
        <p>Fragilidade &#233; um preditor importante e independente de mortalidade, perman&#234;ncia hospitalar mais prolongada, aumento do risco de sangramento e morbidade na popula&#231;&#227;o idosa com SCA.<xref ref-type="bibr" rid="B164"><sup>164</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B165"><sup>165</sup></xref> O decl&#237;nio funcional no idoso &#233; preditor de m&#225; evolu&#231;&#227;o.<xref ref-type="bibr" rid="B166"><sup>166</sup></xref> O escore Gold Standards Framework (GSF), que associa crit&#233;rios de fase final de doen&#231;as, se mostrou preditor independente de eventos n&#227;o cardiovasculares em SCA, enquanto o escore GRACE demonstrou ser um &#243;timo preditor de eventos cardiovasculares nos idosos.<xref ref-type="bibr" rid="B167"><sup>167</sup></xref> A radiografia de t&#243;rax, o ecocardiograma transtor&#225;cico em repouso, a cintilografia mioc&#225;rdica, a angiotomografiqa coron&#225;ria, a resson&#226;ncia magn&#233;tica card&#237;aca e a CATE seguem as mesmas indica&#231;&#245;es dos pacientes mais jovens para o diagn&#243;stico da SCA neste grupo et&#225;rio.<xref ref-type="bibr" rid="B156"><sup>156</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B157"><sup>157</sup></xref></p>
      </sec>
      <sec>
        <title>3.2. Peculiaridades no Tratamento</title>
        <p>Embora os idosos representem a popula&#231;&#227;o que mais se beneficia com as estrat&#233;gias mais agressivas, apresentam maior risco de sangramento, com o dobro da mortalidade dos mais jovens (&lt; 75 anos de idade). Maior mortalidade intra-hospitalar bem como maior taxa de sangramento com a terapia trombol&#237;tica fazem parte deste cen&#225;rio. A abordagem da SCA em pacientes idosos deve ser individualizada, com base nos riscos de complica&#231;&#245;es, expectativa de vida estimada, comorbidades, qualidade de vida e desejo e prefer&#234;ncia do paciente.<xref ref-type="bibr" rid="B153"><sup>153</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B154"><sup>154</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B156"><sup>156</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B157"><sup>157</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B168"><sup>168</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B170"><sup>170</sup></xref> Os pacientes idosos (&gt; 75 anos de idade) com s&#237;ndrome coronariana aguda com supradesnivelamento do segmento ST (SCACSST) e sem supradesnivelamento do segmento ST (SCASSST) devem seguir a mesma abordagem diagn&#243;stica e terap&#234;utica dos mais jovens, baseada em diretrizes e consensos, devendo-se avaliar particularidades de farmacocin&#233;tica, sensibilidade e efeitos colaterais dos f&#225;rmacos, considerando-se sempre o peso e o clearance de creatinina.<xref ref-type="bibr" rid="B170"><sup>170</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B153"><sup>153</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B154"><sup>154</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B156"><sup>156</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B157"><sup>157</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B168"><sup>168</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B170"><sup>170</sup></xref></p>
        <p>Nos &#250;ltimos 15 anos houve um aumento significativo nas taxas de utiliza&#231;&#227;o da terapia farmacol&#243;gica baseada em evid&#234;ncias para pacientes com SCA em todas as faixas et&#225;rias. No entanto, na SCACSST, os pacientes mais idosos apresentam menor chance de receber angioplastia prim&#225;ria, tromb&#243;lise, assim como a prescri&#231;&#227;o de AAS, clopidogrel, betabloqueadores, estatinas ou IECA.<xref ref-type="bibr" rid="B171"><sup>171</sup></xref> O <italic>Study of Global Ageing and Adult Health</italic> (SAGE) comparou os efeitos da terapia intensiva (atorvastatina 80 mg) versus a terapia moderada (pravastatina 40 mg) com estatinas na redu&#231;&#227;o da isquemia mioc&#225;rdica em pacientes idosos entre 65 e 85 anos de idade. Ambos os regimes de estatina foram igualmente eficazes na redu&#231;&#227;o da frequ&#234;ncia e da dura&#231;&#227;o da isquemia, por&#233;m a terapia intensiva com atorvastatina demonstrou ser mais eficaz na redu&#231;&#227;o dos lip&#237;dios e na redu&#231;&#227;o de morte por todas as causas quando comparada &#224; pravastatina.<xref ref-type="bibr" rid="B170"><sup>170</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B172"><sup>172</sup></xref> Entretanto, devido &#224; preval&#234;ncia de efeitos colaterais e de intoler&#226;ncia ao medicamento nessa faixa et&#225;ria, sugere-se estatina nas SCA em doses mais baixas at&#233; atingir um LDL-c &lt; 70 mg/dL, mantendo-se a dose tolerada.</p>
        <p>Acima dos 85 anos de idade, estudos sugerem benef&#237;cio associado das estrat&#233;gias de reperfus&#227;o na SCACSST. A escolha entre fibrinol&#237;ticos ou angioplastia &#233; determinada pela presen&#231;a ou aus&#234;ncia de choque cardiog&#234;nico, tempo de apresenta&#231;&#227;o e comorbidades, que muitas vezes inclinam para angioplastia em idosos. A seguran&#231;a e a efic&#225;cia da reperfus&#227;o, especificamente a terapia fibrinol&#237;tica, nos muito idosos (&#8805; 85 anos de idade) s&#227;o quest&#245;es que exigem investiga&#231;&#227;o aprofundada.<xref ref-type="bibr" rid="B173"><sup>173</sup></xref> O Eighty Study avaliou 457 pacientes com idade &gt; 80 anos com SCASSST (IAM e angina inst&#225;vel) que foram randomizados para estrat&#233;gia invasiva versus conservadora, sugerindo superioridade da terapia invasiva, com maior incid&#234;ncia de morte, infarto, revasculariza&#231;&#227;o de urg&#234;ncia e AVE no grupo de terapia conservadora. Os mesmos resultados foram obtidos no subgrupo dos idosos &gt; 90 anos de idade.<xref ref-type="bibr" rid="B174"><sup>174</sup></xref></p>
      </sec>
      <sec>
        <title>3.3. Recomenda&#231;&#245;es Gerais &#8211; S&#237;ndrome Coronariana Aguda nos Idosos</title>
        <p>Idoso com SCA significa, para o cardiologista, enfrentar tr&#234;s grandes desafios:</p>
        <table-wrap id="t19">
          <table frame="hsides" rules="groups">
            <colgroup width="100%">
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr>
                <th align="left" valign="top">1&#186; Desafio: resumo dos desafios diagn&#243;sticos no idoso</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top">Apresenta&#231;&#227;o at&#237;pica: menos dor t&#237;pica e mais equivalentes anginosos (dispneia, s&#237;ncope, AVE, IC etc.)</td>
              </tr>
              <tr>
                <td align="left" valign="top">Maior gravidade: apresentam-se com mais IC e choque cardiog&#234;nico</td>
              </tr>
              <tr>
                <td align="left" valign="top">Maior preval&#234;ncia de morbimortalidade: reinfarto, AVE, hemorragias maiores e morte</td>
              </tr>
              <tr>
                <td align="left" valign="top">Menor a&#231;&#227;o dos fatores de risco e maior a import&#226;ncia das comorbidades</td>
              </tr>
              <tr>
                <td align="left" valign="top">ECG inespec&#237;fico em 43% dos idosos &gt; 85 anos de idade</td>
              </tr>
              <tr>
                <td align="left" valign="top">Infarto do mioc&#225;rdio (SCACSST) deve ser fortemente suspeitado em mulheres, diab&#233;ticos e pacientes idosos com sintomas at&#237;picos</td>
              </tr>
              <tr>
                <td align="left" valign="top">Devido &#224; frequente apresenta&#231;&#227;o at&#237;pica, pacientes idosos (&gt; 75 anos de idade) devem ser investigados para SCASSST com baixo n&#237;vel de suspeita</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <table-wrap id="t20">
          <table frame="hsides" rules="groups">
            <colgroup width="100%">
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr>
                <th align="left" valign="top">2&#186; Desafio: resumo dos desafios de individualiza&#231;&#227;o da abordagem</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top">Popula&#231;&#227;o heterog&#234;nea</td>
              </tr>
              <tr>
                <td align="left" valign="top">Risco moderado a alto nos escores de estratifica&#231;&#227;o de risco mais utilizados (TIMI, GRACE)</td>
              </tr>
              <tr>
                <td align="left" valign="top">Tratamento deve considerar sa&#250;de geral, comorbidades, estado cognitivo, expectativa de vida, fragilidade, desejos e prefer&#234;ncias do paciente</td>
              </tr>
              <tr>
                <td align="left" valign="top">Aten&#231;&#227;o &#224;s altera&#231;&#245;es farmacocin&#233;ticas do idoso e sensibilidade para os f&#225;rmacos hipotensivos</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <table-wrap id="t21">
          <table frame="hsides" rules="groups">
            <colgroup width="100%">
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr>
                <th align="left" valign="top">3&#186; Desafio: resumo dos desafios de tratamento</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top">Tratar pacientes idosos (&#8805; 75 anos de idade) com terapia medicamentosa, estrat&#233;gia invasiva precoce e revasculariza&#231;&#227;o quando indicado, conforme diretrizes</td>
              </tr>
              <tr>
                <td align="left" valign="top">Deve-se ter aten&#231;&#227;o ao ajuste da dose dos antitromb&#243;ticos nos idosos e nos pacientes com insufici&#234;ncia renal</td>
              </tr>
              <tr>
                <td align="left" valign="top">Recomenda-se adaptar o tratamento antitromb&#243;tico de acordo com o peso e o clearance de creatinina</td>
              </tr>
              <tr>
                <td align="left" valign="top">Estrat&#233;gia medicamentosa intensiva e estrat&#233;gia intervencionista de revasculariza&#231;&#227;o devem sempre ser consideradas, observando-se os efeitos adversos dessas terapias</td>
              </tr>
              <tr>
                <td align="left" valign="top">Ajuste de doses de betabloqueadores, IECA, BRA e estatinas devem ser considerados, visando diminuir ou evitar efeitos colaterais</td>
              </tr>
              <tr>
                <td align="left" valign="top">Considerar estrat&#233;gia invasiva e, se apropriado, a revasculariza&#231;&#227;o, ap&#243;s avalia&#231;&#227;o cuidadosa de riscos e benef&#237;cios potenciais, expectativa de vida estimada, comorbidades, qualidade de vida, fragilidade e prefer&#234;ncias do paciente</td>
              </tr>
              <tr>
                <td align="left" valign="top">&#201; razo&#225;vel escolher cirurgia de revasculariza&#231;&#227;o mioc&#225;rdica &#224; angioplastia em pacientes mais idosos, particularmente aqueles com diabetes ou doen&#231;a de m&#250;ltiplos vasos, devido ao aumento da sobrevida e redu&#231;&#227;o dos eventos cardiovasculares</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN6a">
              <p><italic>AVE: acidente vascular encef&#225;lico; BRA: bloqueador do receptor de angiotensina; GRACE: Global Registry of Acute Coronary Events; IC: insufici&#234;ncia card&#237;aca; IECA: inibidor da enzima conversora da angiotensina; SCACSST: s&#237;ndrome coronariana aguda com supradesnivelamento do segmento ST; SCASSST: s&#237;ndrome coronariana aguda sem supradesnivelamento do segmento ST; TIMI: Thrombolysis in Myocardial Infarction</italic>.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <table-wrap id="t22">
          <table frame="hsides" rules="groups">
            <colgroup width="25%">
              <col/>
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr>
                <th align="left" valign="top">Interven&#231;&#227;o</th>
                <th align="center" valign="top">Recomenda&#231;&#227;o</th>
                <th align="center" valign="top">Classe de recomenda&#231;&#227;o</th>
                <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top">Oxig&#234;nio</td>
                <td align="center" valign="top">Para pacientes com satura&#231;&#227;o arterial menor que 90%, na insufici&#234;ncia respirat&#243;ria ou naqueles com alto risco para hipoxemia, devendo ser mantido nas primeiras 6h ou at&#233; estabiliza&#231;&#227;o hemodin&#226;mica</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">Nitrato</td>
                <td align="center" valign="top">Na apresenta&#231;&#227;o sublingual, &#233; indicado para pacientes com dor tor&#225;cica de tipo isqu&#234;mico. Pode ser utilizada na apresenta&#231;&#227;o intravenosa naqueles idosos com dor persistente, al&#233;m dos quadros associados a hipertens&#227;o e insufici&#234;ncia card&#237;aca. Evitar nos quadros de hipotens&#227;o, infarto de ventr&#237;culo direito e estenose a&#243;rtica grave</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">Morfina</td>
                <td align="center" valign="top">Deve ser reservada para aqueles pacientes com um n&#237;vel inaceit&#225;vel de dor. Dose inicial de 2 a 4 mg, com incrementos de 2 a 8 mg repetidos em intervalos de 5 a 15 minutos</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">Betabloqueadores</td>
                <td align="center" valign="top">Grandes benef&#237;cios quando comparado com grupo mais jovem na preven&#231;&#227;o de SCA e morte. A administra&#231;&#227;o por via intravenosa deve ser usada apenas em casos espec&#237;ficos</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">IECA</td>
                <td align="center" valign="top">Benef&#237;cios especialmente em ICC ou disfun&#231;&#227;o do VE</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">A</td>
              </tr>
              <tr>
                <td align="left" valign="top" rowspan="2">Estatinas</td>
                <td align="center" valign="top">O tratamento da dislipidemia no idoso at&#233; os 75 anos de idade deve seguir as mesmas orienta&#231;&#245;es do n&#227;o idoso</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">A</td>
              </tr>
              <tr>
                <td align="center" valign="top">Ap&#243;s os 75 anos, as doses de hipolipemiantes devem ser individualizadas de acordo com a presen&#231;a de comorbidades, a expectativa de vida e o uso de polifarm&#225;cia</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">AAS</td>
                <td align="center" valign="top">Indicada para todos os idosos se n&#227;o houver contraindica&#231;&#245;es. Benef&#237;cios s&#227;o maiores nos idosos</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">A</td>
              </tr>
              <tr>
                <td align="left" valign="top">Clopidogrel</td>
                <td align="center" valign="top">Indicado em idosos com SCA de alto risco, especialmente os que v&#227;o ser submetidos a angioplastia. A dose de ataque n&#227;o &#233; recomendada nos idosos eleg&#237;veis &#224; terapia trombol&#237;tica</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">A</td>
              </tr>
              <tr>
                <td align="left" valign="top">Ticagrelor</td>
                <td align="center" valign="top">Evolu&#231;&#227;o melhor do que com clopidogrel comparando acima e abaixo de 75 anos, sem diferen&#231;as de sangramento nos 2 grupos</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Prasugrel</td>
                <td align="center" valign="top">Contraindicado em pacientes com idade &#8805; 75 anos, peso &lt; 60 kg e hist&#243;ria de AVE/AIT</td>
                <td align="center" valign="top">III</td>
                <td align="center" valign="top">A</td>
              </tr>
              <tr>
                <td align="left" valign="top">Antitromb&#237;nicos</td>
                <td align="center" valign="top">Devem ser administrados com cautela em pacientes com SCA. Enoxaparina pode ser administrada em dose reduzida para aqueles &gt; 75 anos (0,75 mg/kg, SC, 12/12h)</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">A</td>
              </tr>
              <tr>
                <td align="left" valign="top" rowspan="2">Inibidor da glicoprote&#237;na IIb/IIIa</td>
                <td align="center" valign="top">Indicado nos subgrupos dos mais idosos no momento da interven&#231;&#227;o, excluindo insufici&#234;ncia renal: SCASSST &#8211; Na estrat&#233;gia intervencionista precoce quando n&#227;o se administra tienopirid&#237;nico</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">A</td>
              </tr>
              <tr>
                <td align="center" valign="top">SCASSST &#8211; Na estrat&#233;gia conservadora</td>
                <td align="center" valign="top">IIa</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">Trombol&#237;tico</td>
                <td align="center" valign="top">Quando indicado, avaliar com aten&#231;&#227;o as contraindica&#231;&#245;es, pois estas s&#227;o mais frequentes em idosos. Se utilizar tenecteplase em idosos &gt; 75 anos, aplicar metade da dose</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">A</td>
              </tr>
              <tr>
                <td align="left" valign="top">Angioplastia prim&#225;ria</td>
                <td align="center" valign="top">Melhor risco &#215; benef&#237;cio comparado ao trombol&#237;tico</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">A</td>
              </tr>
              <tr>
                <td align="left" valign="top" rowspan="2">Cateterismo precoce</td>
                <td align="center" valign="top">Melhora da evolu&#231;&#227;o a curto e longo prazos. Evid&#234;ncias de trabalhos randomizados e controlados s&#227;o limitadas nos idosos e deve-se levar em conta o risco de sangramento. Faltam dados no subgrupo &#8805; 80 anos SCACSST &#8211; Pacientes idosos devem ser considerados para a estrat&#233;gia invasiva precoce com a op&#231;&#227;o de poss&#237;vel revasculariza&#231;&#227;o</td>
                <td align="center" valign="top">IIa</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="center" valign="top">SCASSST &#8211; Pacientes idosos devem ser tratados com a terapia medicamentosa orientada nas diretrizes, estrat&#233;gia invasiva precoce e revasculariza&#231;&#227;o quando indicado</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">A</td>
              </tr>
              <tr>
                <td align="left" valign="top">Reabilita&#231;&#227;o card&#237;aca</td>
                <td align="center" valign="top">Mesmos benef&#237;cios que no grupo mais jovem na preven&#231;&#227;o da morte</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">B</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN7a">
              <p><italic>AAS: &#225;cido acetilsalic&#237;lico; AIT: ataque isqu&#234;mico transit&#243;rio; AVE: acidente vascular encef&#225;lico; ICC: insufici&#234;ncia card&#237;aca congestiva; IECA: inibidor da enzima conversora da angiotensina; SCA: s&#237;ndrome coronariana aguda; SCACSST: s&#237;ndrome coronariana aguda com supradesnivelamento do segmento ST; SCASSST: s&#237;ndrome coronariana aguda sem supradesnivelamento do segmento ST; VE: ventr&#237;culo esquerdo</italic>.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
    </sec>
    <sec>
      <title>4. Insufici&#234;ncia Card&#237;aca</title>
      <sec>
        <title>4.1. Peculiaridades no Diagn&#243;stico da Insufici&#234;ncia Card&#237;aca no Idoso</title>
        <p>Pacientes idosos podem ter apresenta&#231;&#245;es at&#237;picas da IC devido a altera&#231;&#245;es cognitivas, sedentarismo, limita&#231;&#245;es funcionais e presen&#231;a de comorbidades. Esses fatores contribuem para um diagn&#243;stico tardio, da&#237; a import&#226;ncia dos exames complementares (<xref ref-type="fig" rid="f1">Figura 1</xref>).<xref ref-type="bibr" rid="B175"><sup>175</sup></xref> O uso de biomarcadores, tais como pept&#237;dio natriur&#233;tico cerebral (BNP), com valores ambulatoriais inferiores a 35 ng/mL exclui a presen&#231;a de IC em indiv&#237;duos sintom&#225;ticos. J&#225; em indiv&#237;duos com dispneia aguda na sala de emerg&#234;ncia, valores de BNP superiores a 250 ng/mL ou de pr&#243;-BNP maiores que 1.800 ng/mL apontam para IC como a causa dos sintomas. Pacientes idosos apresentam n&#237;veis mais elevados de pept&#237;dios natriur&#233;ticos bem como presen&#231;a de comorbidades, por exemplo, insufici&#234;ncia renal, que podem elevar os valores.<xref ref-type="bibr" rid="B176"><sup>176</sup></xref> O resultado de um ECG normal pode ser &#250;til para tornar a hip&#243;tese de IC menos prov&#225;vel, enquanto os achados de FA, bloqueio completo do ramo esquerdo, &#225;reas inativas e hipertrofia do ventr&#237;culo esquerdo (VE)aumentam a probabilidade da doen&#231;a.<xref ref-type="bibr" rid="B176"><sup>176</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B177"><sup>177</sup></xref> Altera&#231;&#245;es na geometria e estrutura card&#237;aca ocorrem com envelhecimento, h&#225; diminui&#231;&#227;o da base para &#225;pice, desvio para direita, dilata&#231;&#227;o do anel a&#243;rtico e aumento da espessura do septo interventricular, levando ao chamado septo sigmoide que pode ocasionar obstru&#231;&#227;o via de sa&#237;da.<xref ref-type="bibr" rid="B176"><sup>176</sup></xref> Apesar de os pacientes com IC com fra&#231;&#227;o de eje&#231;&#227;o reduzida (ICFEr) (FEVE &lt; 40%) e IC com fra&#231;&#227;o de eje&#231;&#227;o preservada (ICFEp) (FEVE &gt; 50%) estarem bem caracterizados, a incerteza existe nos pacientes idosos com IC moderada (FEVE 41% a 49%) . Estudo recente demonstrou que esse perfil intermedi&#225;rio &#233; uma entidade distinta e deve ser categorizada como ICFEr devido &#224; elevada preval&#234;ncia de doen&#231;a coron&#225;ria e aos benef&#237;cios similares do tratamento padr&#227;o guiado por biomarcador.<xref ref-type="bibr" rid="B178"><sup>178</sup></xref> O estudo ecocardiogr&#225;fico permite uma avalia&#231;&#227;o do volume indexado do &#225;trio esquerdo (AE), a presen&#231;a da hipertrofia de VE, a an&#225;lise das press&#245;es de enchimento (rela&#231;&#227;o E/A, rela&#231;&#227;o E/E&#8217; e do fluxo pulmonar), da fun&#231;&#227;o diast&#243;lica, a varia&#231;&#227;o da veia cava inferior, a avalia&#231;&#227;o da PA pulmonar, o grau da regurgita&#231;&#227;o mitral e a presen&#231;a ou n&#227;o de estenose a&#243;rtica (EAo) (em particular o fen&#243;tipo de baixo fluxo, baixo gradiente e com fra&#231;&#227;o de eje&#231;&#227;o normal). Ao lado disso, a busca da etiologia, sendo a amiloidose senil, hoje, uma condi&#231;&#227;o crescente nos indiv&#237;duos acima dos 70 anos de idade.<xref ref-type="bibr" rid="B176"><sup>176</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B177"><sup>177</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B179"><sup>179</sup></xref> Na pr&#225;tica cl&#237;nica a avalia&#231;&#227;o do estado funcional utilizando ergoespirometria auxilia na avalia&#231;&#227;o progn&#243;stica e no planejamento da reabilita&#231;&#227;o card&#237;aca. Presen&#231;a de fibrose, hipertrofia card&#237;aca, dilata&#231;&#227;o das c&#226;maras card&#237;acas, trombo intracard&#237;aco, espessamento peric&#225;rdico, al&#233;m de estudo da fun&#231;&#227;o do ventr&#237;culo direito (VD) podem ser avaliados pela resson&#226;ncia card&#237;aca. Ela tem se tornado parte integrante na avalia&#231;&#227;o dos pacientes com doen&#231;a mioc&#225;rdica, identificando a causa &#8211; inflama&#231;&#227;o (miocardite), amiloidose, sarcoidose, doen&#231;a de Chagas; cardiomiopatias e doen&#231;a isqu&#234;mica.<xref ref-type="bibr" rid="B176"><sup>176</sup></xref> A cintilografia mioc&#225;rdica &#233; um m&#233;todo &#250;til em indiv&#237;duos com suspeita de cardiopatia isqu&#234;mica com disfun&#231;&#227;o sist&#243;lica; &#233; solicitada para investigar isquemia e/ou viabilidade mioc&#225;rdica. A cintilografia &#243;ssea pelo pirofostato de tecn&#233;cio pode ser &#250;til no diagn&#243;stico de amiloidose card&#237;aca por transtirretina em idosos com hipertrofia e IC.<xref ref-type="bibr" rid="B176"><sup>176</sup></xref></p>
        <fig id="f1">
          <label>Figura 1</label>
          <caption>
            <title><italic>Fluxograma diagn&#243;stico. IC: insufici&#234;ncia card&#237;aca; ICFEr: insufici&#234;ncia card&#237;aca com fra&#231;&#227;o de eje&#231;&#227;o reduzida; ICFEp: insufici&#234;ncia card&#237;aca com fra&#231;&#227;o de eje&#231;&#227;o compensada</italic>.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-112-05-0649-90086-gf01.tif"/></fig>
      </sec>
      <sec>
        <title>4.2. Peculiaridades no Tratamento da Insufici&#234;ncia Card&#237;aca no Idoso</title>
        <p>IC &#233; prevalente entre os idosos, afetando at&#233; 20% dos pacientes &gt; 75 anos de idade.<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> Caracteriza-se por apresentar-se com disfun&#231;&#227;o sist&#243;lica (ICFEr) ou disfun&#231;&#227;o diast&#243;lica (ICFEp) e com alta mortalidade (2 vezes o risco de morte por todas as causas ajustado pela idade e sexo e 4 vezes o risco de morte cardiovascular).<xref ref-type="bibr" rid="B180"><sup>180</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B181"><sup>181</sup></xref> Nas &#250;ltimas duas d&#233;cadas a apresenta&#231;&#227;o de ICFEp tem se tornado o principal fen&#243;tipo cl&#237;nico.<xref ref-type="bibr" rid="B2"><sup>2</sup></xref></p>
        <p>A polifarm&#225;cia &#233; extremamente comum nesse contexto, com grande impacto das intera&#231;&#245;es medicamentosas, taxas mais elevadas de efeitos adversos e m&#225; ades&#227;o; portanto, programas multidisciplinares e de ades&#227;o mostraram-se &#250;teis nesse grupo de pacientes.<xref ref-type="bibr" rid="B182"><sup>182</sup></xref> O pr&#243;prio exerc&#237;cio em compara&#231;&#227;o com os cuidados habituais, em doentes idosos com ICFEr e classes funcionais II e III da <italic>New York Heart Association</italic>(NYHA), mostrou-se seguro, sem aumento de mortalidade e hospitaliza&#231;&#245;es, com melhora do teste de caminhada.<xref ref-type="bibr" rid="B183"><sup>183</sup></xref></p>
        <p>Os objetivos do tratamento farmacol&#243;gico da IC s&#227;o: redu&#231;&#227;o de mortalidade e interna&#231;&#227;o; melhora da capacidade funcional e qualidade de vida; e inclui o uso de IECA, BRA, betabloqueadores e antagonistas da aldosterona. Os idosos t&#234;m sido frequentemente exclu&#237;dos ou sub-representados nos estudos realizados em pacientes com IC.<xref ref-type="bibr" rid="B184"><sup>184</sup></xref></p>
        <p>V&#225;rios ensaios marcantes demonstraram a efic&#225;cia dos IECA em pacientes mais jovens (m&#233;dia de idade 60/66 anos), por&#233;m uma an&#225;lise de subgrupos do estudo <italic>Heart Outcomes Prevention Evaluation</italic> (HOPE) demonstrou maior redu&#231;&#227;o do risco em pacientes &gt; 65 anos quando comparada ao grupo mais jovem.<xref ref-type="bibr" rid="B184"><sup>184</sup></xref></p>
        <p>Os BRA foram pouco avaliados em pacientes idosos, por&#233;m em suban&#225;lise do estudo <italic>Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity</italic> (CHARM-Alternative), com 23,3% da popula&#231;&#227;o do estudo em idade &#8805; 75 anos, demonstraram-se benef&#237;cios semelhantes aos relatados para o grupo geral.<xref ref-type="bibr" rid="B185"><sup>185</sup></xref></p>
        <p>Quanto aos betabloqueadores, metan&#225;lise recente de 12.719 pacientes n&#227;o encontrou diferen&#231;a no benef&#237;cio entre aqueles definidos como &#8220;idosos&#8221; nos ensaios constituintes e seus hom&#243;logos mais jovens. Importante ressaltar que o paciente mais velho nos ensaios individuais analisados tinha 71 anos de idade.<xref ref-type="bibr" rid="B5"><sup>5</sup></xref> O <italic>Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure</italic> (SENIORS) demonstrou a efic&#225;cia do nebivolol em pacientes &gt; 70 anos de idade com ICC. Suban&#225;lise do estudo <italic>Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure</italic> (OPTIMIZE-HF) evidenciou que os betabloqueadores podem estar associados a efeitos ben&#233;ficos em pacientes &#8805; 75&#160;anos de idade.<xref ref-type="bibr" rid="B186"><sup>186</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B187"><sup>187</sup></xref></p>
        <p>O registro Euro HF I sugeriu que o uso de IECA e/ou betabloqueadores est&#225; associado a redu&#231;&#227;o significativa na mortalidade a curto prazo em octogen&#225;rios. No entanto, o Euro HF Survey II n&#227;o mostrou melhora na mortalidade em um ano com o uso de betabloqueadores, possivelmente relacionado ao maior n&#250;mero de pacientes idosos com ICFEp neste estudo.<xref ref-type="bibr" rid="B188"><sup>188</sup></xref></p>
        <p>Nos estudos mais importantes com antagonistas da aldosterona [<italic>Randomized Aldactone Evaluation Study</italic> (RALES) e <italic>Epleronone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study</italic> [EPHESUS]) a idade m&#233;dia dos pacientes era de, respectivamente, 67 e 64 anos. No entanto, seu uso em idosos deve ser cuidadosamente monitorado em fun&#231;&#227;o da disfun&#231;&#227;o renal e da intera&#231;&#227;o medicamentosa subjacente. No estudo <italic>Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure</italic> (PARADIGM) a hipotens&#227;o sintom&#225;tica em pacientes &gt; 75 anos de idade foi mais frequente no grupo sacubitril/valsartana (18%) contra 12% grupo enalapril.<xref ref-type="bibr" rid="B189"><sup>189</sup></xref></p>
        <p>Em suma, as orienta&#231;&#245;es atuais recomendam uma abordagem terap&#234;utica semelhante &#224; aplicada aos mais jovens para o tratamento da IC, com cuidado para intera&#231;&#245;es e tolerabilidade.<xref ref-type="bibr" rid="B176"><sup>176</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B190"><sup>190</sup></xref></p>
      </sec>
      <sec>
        <title>4.3. Recomenda&#231;&#245;es Gerais na Insufici&#234;ncia Card&#237;aca no Idoso</title>
        <table-wrap id="t23">
          <table frame="hsides" rules="groups">
            <colgroup width="33%">
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr>
                <th align="left" valign="top">M&#233;todos complementares diagn&#243;sticos em ICC no idoso</th>
                <th align="center" valign="top">Classe de recomenda&#231;&#227;o</th>
                <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top">Eco transtor&#225;cico recomendado para avalia&#231;&#227;o de estrutura e fun&#231;&#227;o com IC e estabelecer o diagn&#243;stico de ICFEr e/ou ICFEp</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">Eco transtor&#225;cico recomendado para avalia&#231;&#227;o para candidatos a ressincroniza&#231;&#227;o/CDI</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">Repetir avalia&#231;&#227;o de fun&#231;&#227;o ventricular e medidas de remodelamento estrutural em pacientes com ICC e mudan&#231;a de estado cl&#237;nico ou em caso de descompensa&#231;&#227;o</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">RM com realce tardio deve ser considerada em pacientes com miocardiopatia dilatada para diferenciar entre etiologia isqu&#234;mica e n&#227;o isqu&#234;mica</td>
                <td align="center" valign="top">IIa</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">RM recomendada na caracteriza&#231;&#227;o de tecido card&#237;aco na suspeita de miocardite, amiloidose, sarcoidose, mioc&#225;rdio n&#227;o compactado</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">Exames de imagens de estresse n&#227;o invasivos (resson&#226;ncia, eco, SPECT, PET) na avalia&#231;&#227;o de isquemia mioc&#225;rdica e viabilidade em pacientes com DAC e ICC antes de decis&#227;o de revasculariza&#231;&#227;o</td>
                <td align="center" valign="top">IIb</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Cinecoronariografia recomendada em pacientes com ICC e angina para diagn&#243;stico de DAC</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">Angiotomografia coron&#225;ria em pacientes com ICC e probabilidade pr&#233;-teste indicando risco baixo ou intermedi&#225;rio e em pacientes com exames n&#227;o invasivos de estresse sugestivos de DAC com objetivo de excluir exames invasivos</td>
                <td align="center" valign="top">IIb</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">Hemograma, s&#243;dio, pot&#225;ssio, ureia, creatinina (<italic>clearance</italic>), fun&#231;&#227;o hep&#225;tica, glicose, hemoglobina glicosilada, TSH, ferritina</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">Pept&#237;dios natriur&#233;ticos</td>
                <td align="center" valign="top">IIa</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">Eletrocardiograma recomendado para avalia&#231;&#227;o e ritmo, frequ&#234;ncia card&#237;aca, morfologia e dura&#231;&#227;o do QRS</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">Radiografia de t&#243;rax recomendada para excluir altera&#231;&#245;es pulmonares. Nos quadros de descompensa&#231;&#227;o aguda para detectar edema/congest&#227;o pulmonar</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">C</td>
              </tr>
              <tr>
                <td align="left" valign="top">Bi&#243;psia endomioc&#225;rdica deve ser considerada, para diagn&#243;stico de causas espec&#237;ficas em casos de piora r&#225;pida e progressiva a despeito da terap&#234;utica padr&#227;o</td>
                <td align="center" valign="top">IIa</td>
                <td align="center" valign="top">C</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN8a">
              <p><italic>CDI: cardioversor-desfibrilador implant&#225;vel; DAC: doen&#231;a arterial coronariana; IC: insufici&#234;ncia card&#237;aca; ICC: insufici&#234;ncia card&#237;aca congestiva; ICFEp insufici&#234;ncia card&#237;aca com fra&#231;&#227;o de eje&#231;&#227;o compensada; ICFEr: insufici&#234;ncia card&#237;aca com fra&#231;&#227;o de eje&#231;&#227;o reduzida; PET: tomografia por emiss&#227;o de p&#243;sitrons; RM: resson&#226;ncia magn&#233;tica; SPECT: tomografia computadorizada por emiss&#227;o de f&#243;ton &#250;nico; TSH: horm&#244;nio tireoestimulante</italic>.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <table-wrap id="t24">
          <table frame="hsides" rules="groups">
            <colgroup width="33%">
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr>
                <th align="left" valign="top" colspan="3">Grau de recomenda&#231;&#227;o tratamento farmacol&#243;gico ICFEr CF II a IV</th>
              </tr>
              <tr>
                <th align="left" valign="middle">Recomenda&#231;&#227;o</th>
                <th align="center" valign="top">Classe de recomenda&#231;&#227;o</th>
                <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top">IECA em conjunto a betabloqueador com objetivo de redu&#231;&#227;o de mortalidade e hospitaliza&#231;&#227;o</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">A</td>
              </tr>
              <tr>
                <td align="left" valign="top">BRA em conjunto com betabloqueador com objetivo de redu&#231;&#227;o de hospitaliza&#231;&#227;o e mortalidade em pacientes intolerantes ao IECA</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Adi&#231;&#227;o do bloqueador da aldosterona em pacientes sintom&#225;ticos, com FEVE &#8804; 35%, associado ao IECA (ou BRA) e betabloqueador</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">A</td>
              </tr>
              <tr>
                <td align="left" valign="top">Diur&#233;ticos para melhora dos sintomas em pacientes com congest&#227;o</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Bloqueador do receptor da angiotensina/neprilisina (sacubitril/valsartana), como substituto ao IECA para reduzir mortalidade e hospitaliza&#231;&#227;o em pacientes que se mant&#234;m sintom&#225;ticos a despeito tratamento com IECA (ou BRA) e betabloqueador</td>
                <td align="center" valign="top">I</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Hidralazina e dinidrato de isossorbida em pacientes afro-americanos com FE &lt; 35% ou FE &lt; 45% com dilata&#231;&#227;o ventricular que se mant&#234;m sintom&#225;ticos em CF III-IV a despeito do tratamento com IECA (ou BRA) e betabloqueador para reduzir mortalidade e hospitaliza&#231;&#227;o</td>
                <td align="center" valign="top">IIa</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Hidralazina e dinidrato em pacientes sintom&#225;ticos com ICFEr que n&#227;o toleram IECA ou BRA para reduzir mortalidade</td>
                <td align="center" valign="top">IIb</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Digoxina em pacientes sintom&#225;ticos em ritmo sinusal a despeito de tratamento com IECA (ou BRA) e betabloqueador para reduzir hospitaliza&#231;&#227;o</td>
                <td align="center" valign="top">IIb</td>
                <td align="center" valign="top">B</td>
              </tr>
              <tr>
                <td align="left" valign="top">Inibidor do canal de &#237;ons If (ivabradina) pode ser usado em pacientes sintom&#225;ticos em ritmo sinusal com FE &lt; 35% e FC &gt; 70 bpm a despeito de tratamento com IECA (ou BRA) e betabloqueador para reduzir hospitaliza&#231;&#227;o e mortalidade</td>
                <td align="center" valign="top">IIa</td>
                <td align="center" valign="top">B</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN9a">
              <p><italic>BRA: bloqueador do receptor de angiotensina; CF: classe funcional da New York Heart Association; FC: frequ&#234;ncia card&#237;aca; FE: fra&#231;&#227;o de eje&#231;&#227;o; FEVE: fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo; ICFEr: insufici&#234;ncia card&#237;aca com fra&#231;&#227;o de eje&#231;&#227;o reduzida; IECA: inibidor da enzima conversora da angiotensina</italic>.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <table-wrap id="t25">
          <table frame="hsides" rules="groups">
            <colgroup width="33%">
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr>
                <th align="left" valign="top" colspan="3">Tratamento de comorbidades</th>
              </tr>
              <tr>
                <th align="left" valign="middle">Recomenda&#231;&#227;o</th>
                <th align="center" valign="top">Classe de recomenda&#231;&#227;o</th>
                <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top">Defici&#234;ncia de ferro &#8211; reposi&#231;&#227;o de ferro IV em pacientes com ferritina &lt; 100 ng/ml ou ferritina entre 100 e 199 ng/ml e satura&#231;&#227;o de transferrina &lt; 20% com objetivo de melhorar sintomas e qualidade de vida</td>
                <td align="center" valign="top">IIa</td>
                <td align="center" valign="top">A</td>
              </tr>
              <tr>
                <td align="left" valign="top">Diabetes &#8211; uso de metformina</td>
                <td align="center" valign="top">IIa</td>
                <td align="center" valign="top">C</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN10a">
              <p><italic>IV: via intravenosa</italic>.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <table-wrap id="t26">
          <table frame="hsides" rules="groups">
            <colgroup width="20%">
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr>
                <th align="left" valign="top" colspan="5">F&#225;rmacos dispon&#237;veis, doses iniciais e dose-alvo, ajuste da dose no idoso e seguran&#231;a</th>
              </tr>
              <tr>
                <th align="left" valign="top">F&#225;rmaco</th>
                <th align="center" valign="top">Dose inicial</th>
                <th align="center" valign="top">Dose m&#225;xima</th>
                <th align="center" valign="top">Ajuste da dose no idoso</th>
                <th align="center" valign="top">Seguran&#231;a no idoso</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="top">Captopril</td>
                <td align="center" valign="top">6,25 mg 3&#215;/dia</td>
                <td align="center" valign="top">50 mg 3&#215;/dia</td>
                <td align="center" valign="top">Nenhum</td>
                <td align="center" valign="top">Aumento de hipotens&#227;o ortost&#225;tica Tomar antes deitar &#224; noite Diminuir diur&#233;tico</td>
              </tr>
              <tr>
                <td align="left" valign="top">Enalapril</td>
                <td align="center" valign="top">2,5 mg 2&#215;/dia</td>
                <td align="center" valign="top">10-20 mg 2&#215;/dia</td>
                <td align="center" valign="top">Nenhum</td>
                <td align="center" valign="top">Mais suscet&#237;vel a disfun&#231;&#227;o renal</td>
              </tr>
              <tr>
                <td align="left" valign="top">Lisinopril</td>
                <td align="center" valign="top">2,5-5,0 mg 1&#215;/dia</td>
                <td align="center" valign="top">20-40 mg 1&#215;/dia</td>
                <td align="center" valign="top">Nenhum</td>
                <td align="center" valign="top">Evitar uso de AINH</td>
              </tr>
              <tr>
                <td align="left" valign="top">Perindopril</td>
                <td align="center" valign="top">2,0 mg 1&#215;/dia</td>
                <td align="center" valign="top">8,0-16 mg 1&#215;/dia</td>
                <td align="center" valign="top">Nenhum</td>
                <td align="center" valign="top"/>
              </tr>
              <tr>
                <td align="left" valign="top">Ramipril</td>
                <td align="center" valign="top">1,25-2,5 mg 1&#215;/dia</td>
                <td align="center" valign="top">10 mg 1&#215;/dia</td>
                <td align="center" valign="top">Ajuste fun&#231;&#227;o renal</td>
                <td align="center" valign="top"/>
              </tr>
              <tr>
                <td align="left" valign="top">Candersatana</td>
                <td align="center" valign="top">4,0-8,0 mg 1&#215;/dia</td>
                <td align="center" valign="top">32 mg</td>
                <td align="center" valign="top">Nenhum mas elevada AUC e C m&#225;x</td>
                <td align="center" valign="top">Similar ao uso de IECA</td>
              </tr>
              <tr>
                <td align="left" valign="top">Losartana</td>
                <td align="center" valign="top">25 mg 1&#215;/dia</td>
                <td align="center" valign="top">50-100 mg</td>
                <td align="center" valign="top">Nenhum</td>
                <td align="center" valign="top"/>
              </tr>
              <tr>
                <td align="left" valign="top">Valsartana</td>
                <td align="center" valign="top">40 mg 2&#215;/dia</td>
                <td align="center" valign="top">320 mg</td>
                <td align="center" valign="top">Nenhum</td>
                <td align="center" valign="top"/>
              </tr>
              <tr>
                <td align="left" valign="top" rowspan="9">Bisoprolol</td>
                <td align="center" valign="top" rowspan="9">1,25 mg 1&#215;/dia</td>
                <td align="center" valign="top" rowspan="9">10 mg 1&#215;/dia</td>
                <td align="center" valign="top" rowspan="9"/>
                <td align="center" valign="top">Reten&#231;&#227;o L&#237;quido:</td>
              </tr>
              <tr>
                <td align="center" valign="top">- Monitorar peso di&#225;rio</td>
              </tr>
              <tr>
                <td align="center" valign="top">- Ajuste de dose de diur&#233;tico</td>
              </tr>
              <tr>
                <td align="center" valign="top">Risco de hipotens&#227;o e bradicardia:</td>
              </tr>
              <tr>
                <td align="center" valign="top">- Iniciar com dose baixa e titular progressivamente</td>
              </tr>
              <tr>
                <td align="center" valign="top">- Adequada hidrata&#231;&#227;o</td>
              </tr>
              <tr>
                <td align="center" valign="top">Aumento da fadiga:</td>
              </tr>
              <tr>
                <td align="center" valign="top">- Melhora com tempo</td>
              </tr>
              <tr>
                <td align="center" valign="top">- Considerar comorbidades anemia</td>
              </tr>
              <tr>
                <td align="left" valign="top">Carvedilol</td>
                <td align="center" valign="top">3,12-5 mg 2&#215;/dia</td>
                <td align="center" valign="top">50 mg/dia</td>
                <td align="center" valign="top">Nenhum</td>
                <td align="center" valign="top"/>
              </tr>
              <tr>
                <td align="left" valign="top">Metropolol, succinato</td>
                <td align="center" valign="top">12,5-25 mg</td>
                <td align="center" valign="top">200 mg/dia</td>
                <td align="center" valign="top">Nenhum</td>
                <td align="center" valign="top"/>
              </tr>
              <tr>
                <td align="left" valign="top">Nebivolol</td>
                <td align="center" valign="top">1,25 mg</td>
                <td align="center" valign="top">10 mg</td>
                <td align="center" valign="top">Nenhum</td>
                <td align="center" valign="top"/>
              </tr>
              <tr>
                <td align="left" valign="top">Espirolactona</td>
                <td align="center" valign="top">12,5-25 mg</td>
                <td align="center" valign="top">25-50 mg</td>
                <td align="center" valign="top">Nenhum</td>
                <td align="center" valign="top">Aumento do risco de hipercalemia e disfun&#231;&#227;o renal Monitorar K e creatinina</td>
              </tr>
              <tr>
                <td align="left" valign="top">Furosemida</td>
                <td align="center" valign="top">20-40 mg/dia 1 ou 2&#215;/dia</td>
                <td align="center" valign="top">600 mg (usual 40-240 mg/dia)</td>
                <td align="center" valign="top">Iniciar 20 mg/dia</td>
                <td align="center" valign="top">Monitoramento frequente Aumento do risco de altera&#231;&#227;o no balan&#231;o h&#237;drico e dist&#250;rbio eletrol&#237;tico</td>
              </tr>
              <tr>
                <td align="left" valign="top">Bumetamida</td>
                <td align="center" valign="top">0,5-1 mg 1 ou 2&#215;/dia</td>
                <td align="center" valign="top">10 mg Usual (1-5 mg/dia)</td>
                <td align="center" valign="top">Nenhum</td>
                <td align="center" valign="top">Monitoramento frequente Aumento do risco de altera&#231;&#227;o no balan&#231;o h&#237;drico e dist&#250;rbio eletrol&#237;tico</td>
              </tr>
              <tr>
                <td align="left" valign="top">Hidroclortiazida</td>
                <td align="center" valign="top">25 mg</td>
                <td align="center" valign="top">200 mg/dia Usual (12,5-100 mg/dia)</td>
                <td align="center" valign="top">Iniciar 12,5 mg-25 mg</td>
                <td align="center" valign="top">Monitoramento do estado vol&#234;mico e eletrol&#237;tico</td>
              </tr>
              <tr>
                <td align="left" valign="top">Clortalidona</td>
                <td align="center" valign="top">12,5-25 mg</td>
                <td align="center" valign="top">100 mg</td>
                <td align="center" valign="top">Nenhum</td>
                <td align="center" valign="top">Monitoramento do estado vol&#234;mico e eletrol&#237;tico</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN11a">
              <p><italic>AINH: anti-inflamat&#243;rio n&#227;o hormonal; AUC: &#225;rea sob a curva; IECA: inibidor da enzima conversora da angiotensina</italic>.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
    </sec>
    <sec>
      <title>5. Hipertens&#227;o Arterial no Idoso</title>
      <sec>
        <title>5.1. Peculiaridades no Diagn&#243;stico</title>
        <p>Estudo epidemiol&#243;gico brasileiro EMI (Estudo Multic&#234;ntrico de Idosos atendidos em ambulat&#243;rios de cardiologia e geriatria de institui&#231;&#245;es brasileiras)<xref ref-type="bibr" rid="B191"><sup>191</sup></xref> demonstrou que a HAS &#233; o principal FR entre os idosos brasileiros. Encontra-se presente em 65% dos idosos ambulatoriais e em 80% das mulheres &gt; 75 anos de idade. O envelhecimento produz altera&#231;&#245;es vasculares, como: enrijecimento arterial, redu&#231;&#227;o de elasticidade e complac&#234;ncia vascular, menor capacidade de vasodilata&#231;&#227;o, aumento da press&#227;o arterial sist&#243;lica (PAS), menor sensibilidade a mudan&#231;as de volume, lentifica&#231;&#227;o do relaxamento ventricular, maior trabalho card&#237;aco, perda de mi&#243;citos e hipertrofia compensat&#243;ria.<xref ref-type="bibr" rid="B192"><sup>192</sup></xref> Essas altera&#231;&#245;es levam a peculiaridades no diagn&#243;stico e tratamento da HAS no idoso.</p>
        <sec>
          <title>5.1.1. Peculiaridades na Aferi&#231;&#227;o da Press&#227;o Arterial</title>
          <p>A PA em idosos apresenta grande variabilidade e deve-se ter cuidados especiais em sua aferi&#231;&#227;o, pela possibilidade a presen&#231;a dos seguintes fatores:</p>
          <list list-type="alpha-lower">
            <list-item>
              <p>HO: definida como a queda de PAS &gt; 20 mmHg ou da press&#227;o arterial diast&#243;lica (PAD) &gt; 10 mmHg, ap&#243;s 3 minutos na posi&#231;&#227;o ortost&#225;tica. Recomenda-se a verifica&#231;&#227;o da PA nas posi&#231;&#245;es sentada, deitada e em p&#233;, pois altera&#231;&#245;es ateroscler&#243;ticas nas regi&#245;es dos seios carot&#237;deos podem reduzir a sensibilidade dos barorreceptores, ocasionando redu&#231;&#227;o dos reflexos posturais, predispondo &#224; HO.<xref ref-type="bibr" rid="B3"><sup>3</sup></xref> Al&#233;m disso, comorbidades como polineuropatia perif&#233;rica, doen&#231;a de Parkinson e uso de f&#225;rmacos como diur&#233;tico, antidepressivo, vasodilatador e betabloqueador podem tamb&#233;m ocasionar HO em at&#233; 34% de idosos &gt; 75 anos de idade.</p>
            </list-item>
            <list-item>
              <p>Hiato auscultat&#243;rio: situa&#231;&#227;o em que, ap&#243;s ausculta do primeiro som de Korotkoff, ocorre desaparecimento total deste som, com reaparecimento ap&#243;s o decr&#233;scimo da PAS, mas antes do in&#237;cio da &#250;ltima fase dos sons de Korotkoff. Isso leva ao diagn&#243;stico err&#244;neo da PAS em n&#237;vel mais baixo, falseando o diagn&#243;stico de normotens&#227;o. Para evitar este erro de aferi&#231;&#227;o, deve-se estimar a press&#227;o sist&#243;lica pela t&#233;cnica palpat&#243;ria do pulso radial e inflar o manguito 20 a 30 mmHg acima deste ponto.<xref ref-type="bibr" rid="B193"><sup>193</sup></xref></p>
            </list-item>
            <list-item>
              <p>Pseudo-hipertens&#227;o: a pseudo-hipertens&#227;o pode surgir em idosos com arteriosclerose pronunciada, calcifica&#231;&#227;o da parede arterial e enrijecimento dos vasos, situa&#231;&#227;o em que a insufla&#231;&#227;o do manguito &#233; insuficiente para colabar a art&#233;ria braquial.<xref ref-type="bibr" rid="B193"><sup>193</sup></xref> Para identifica&#231;&#227;o deste fato, utiliza-se a manobra de Osler, que consiste em inflar o manguito at&#233; n&#237;veis acima da press&#227;o sist&#243;lica e, concomitantemente, palpar a art&#233;ria radial. A persist&#234;ncia da palpabilidade sugere rigidez da art&#233;ria e indica que o &#237;ndice obtido pela ausculta n&#227;o expressa a verdadeira PAS. Pode-se suspeitar tamb&#233;m de pseudo-hipertens&#227;o arterial quando a PAS est&#225; elevada, por&#233;m o paciente n&#227;o apresenta les&#227;o em &#243;rg&#227;os-alvo, ou diante de manifesta&#231;&#245;es de hipotens&#227;o ap&#243;s tratamento com anti-hipertensivos em dose baixa.</p>
            </list-item>
            <list-item>
              <p>Hipertens&#227;o arterial durante exerc&#237;cio: apesar de a PA habitualmente se elevar durante exerc&#237;cio f&#237;sico, este aumento &#233; maior em idosos, devido &#224; rigidez arterial. Valores para diagnosticar HAS durante exerc&#237;cio n&#227;o s&#227;o claros. Pacientes fisicamente descondicionados respondem com maior aumento da PA que pacientes condicionados.</p>
            </list-item>
            <list-item>
              <p>Hipertens&#227;o arterial do avental branco: ocorre quando a press&#227;o se eleva no consult&#243;rio, por&#233;m se mant&#233;m normal durante as atividades rotineiras. Pode ser melhor avaliada pela medida ambulatorial da press&#227;o arterial (MAPA) de 24 horas ou medida residencial da press&#227;o arterial (MRPA).<xref ref-type="bibr" rid="B193"><sup>193</sup></xref> Essa condi&#231;&#227;o pode ser minimizada por meio de aferi&#231;&#245;es seriadas.</p>
            </list-item>
            <list-item>
              <p>Hipertens&#227;o arterial mascarada: aqui ocorre o contr&#225;rio da HAS do avental branco: a press&#227;o se mant&#233;m alta nas atividades rotineiras e normal no consult&#243;rio.<xref ref-type="bibr" rid="B193"><sup>193</sup></xref> Pode tamb&#233;m ser avaliada por MAPA 24h ou MRPA.</p>
            </list-item>
            <list-item>
              <p>Hipertens&#227;o sist&#243;lica isolada (HSI) e press&#227;o de pulso (PP): a HSI e a PP s&#227;o fatores de risco cardiovascular em idosos.<xref ref-type="bibr" rid="B191"><sup>191</sup></xref> A HSI se deve a menores distensibilidade e elasticidade dos vasos de grande capacit&#226;ncia, como a aorta, resultando em aumento da velocidade da onda de pulso (VOP). O aumento da VOP &#233; acompanhado de aumento da velocidade da onda reflexa, que retorna da periferia para a circula&#231;&#227;o central.<xref ref-type="bibr" rid="B191"><sup>191</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B192"><sup>192</sup></xref> Nos idosos, a onda reflexa atinge a aorta ascendente durante a s&#237;stole, levando a aumento ainda maior da PAS. A perda da onda reflexa na protodi&#225;stole faz com que a press&#227;o diast&#243;lica permane&#231;a igual ou diminua.<xref ref-type="bibr" rid="B192"><sup>192</sup></xref> O efeito final consiste no aumento predominante da PAS, com PAD normal, ou at&#233; baixa. Caracter&#237;sticas da HSI: PAS &#8805; 140 mmHg e PAD &lt; 90 mmHg.<xref ref-type="bibr" rid="B193"><sup>193</sup></xref> A PP &#233; definida como a diferen&#231;a entre a PAS e a PAD. Isto ocorre pela progressiva perda de elasticidade arterial, com consequente redu&#231;&#227;o da complac&#234;ncia vascular. A PAD tende a ficar normal ou at&#233; baixa. Os limites para os valores da PP que seriam anormais ainda n&#227;o est&#227;o definidos.<xref ref-type="bibr" rid="B191"><sup>191</sup></xref> O estudo de Framingham demonstrou maior risco cardiovascular associado a maior PP, em pacientes de 50 a 79 anos de idade, al&#233;m da import&#226;ncia da PAD baixa nessa associa&#231;&#227;o.<xref ref-type="bibr" rid="B3"><sup>3</sup></xref> Al&#233;m dos fatores mencionados, deve-se pesquisar les&#245;es em &#243;rg&#227;os-alvo (altera&#231;&#245;es em fundo de olho, hipertrofia de VE, aterosclerose perif&#233;rica e renal) e avaliar a possibilidade de HAS secund&#225;ria. S&#227;o fatores suspeitos:<xref ref-type="bibr" rid="B193"><sup>193</sup></xref></p>
              <list list-type="alpha-lower">
                <list-item>
                  <p>HAS de instala&#231;&#227;o abrupta ou piora aguda</p>
                </list-item>
                <list-item>
                  <p>Sopro abdominal</p>
                </list-item>
                <list-item>
                  <p>HAS resistente a tr&#234;s ou mais f&#225;rmacos</p>
                </list-item>
                <list-item>
                  <p>Aumento da creatinina acima de 30% com o uso de IECA ou de BRA</p>
                </list-item>
                <list-item>
                  <p>Doen&#231;a ateroscler&#243;tica sist&#234;mica em dislipid&#234;micos e fumantes</p>
                </list-item>
                <list-item>
                  <p>Edema pulmonar hipertensivo recorrente</p>
                </list-item>
                <list-item>
                  <p>Feocromocitoma e hiperaldosteronismo devem ser adequadamente investigados com exames mais espec&#237;ficos pois, embora menos frequentes em idosos, uma vez diagnosticados e tratados, podem levar &#224; cura do paciente.</p>
                </list-item>
              </list>
            </list-item>
          </list>
          <p>Entre as causas secund&#225;rias de HAS, destacam-se insufici&#234;ncia a&#243;rtica (IAo), hipertireoidismo, aterosclerose renovascular, uso de f&#225;rmacos que elevam a press&#227;o, como: anti-inflamat&#243;rios n&#227;o hormonais, anti-histam&#237;nicos, descongestionantes, corticosteroides, IMAO, ADT.</p>
        </sec>
        <sec>
          <title>5.1.2. Peculiaridades da Investiga&#231;&#227;o Cl&#237;nico-Laboratorial</title>
          <p>A investiga&#231;&#227;o cl&#237;nico-laboratorial tem como objetivos confirmar eleva&#231;&#227;o da PA, identificar causas da HAS, les&#245;es em &#243;rg&#227;o-alvo, doen&#231;as associadas e estratificar risco cardiovascular. Al&#233;m de hist&#243;ria cl&#237;nica, testes de cogni&#231;&#227;o e exame f&#237;sico, incluindo IMC e circunfer&#234;ncia abdominal, deve-se realizar:</p>
          <list list-type="alpha-lower">
            <list-item>
              <p>ECG de repouso.</p>
            </list-item>
            <list-item>
              <p>Exame de urina (bioqu&#237;mica e sedimento).</p>
            </list-item>
            <list-item>
              <p>Exames de sangue: hemograma, creatinina, pot&#225;ssio, glicemia de jejum, glicohemoglobina, colesterol total e fra&#231;&#245;es, triglicer&#237;deos, &#225;cido &#250;rico. N&#237;veis sangu&#237;neos de creatinina em idosos podem ser normais, apesar da queda da fun&#231;&#227;o renal. Este fato decorre da perda progressiva da massa muscular, principal determinante da produ&#231;&#227;o de creatinina. Assim, n&#237;veis de creatinina &gt; 1,5 mg/dL s&#227;o considerados anormais em idosos. A f&#243;rmula mais utilizada para c&#225;lculo da taxa de filtra&#231;&#227;o glomerular estimada (TFGE) &#233; a de Cockroff-Gault (mL/min): (140 &#8211; idade) &#215; peso (kg)/creatinina plasm&#225;tica (mg/dL) &#215; 72 para homens e 0,85 para mulheres. Interpreta&#231;&#227;o: fun&#231;&#227;o renal normal, &gt; 90 mL/min; disfun&#231;&#227;o renal leve, 60 a 90 mL/min; disfun&#231;&#227;o renal moderada, 30 a 60 mL/min; disfun&#231;&#227;o renal grave, &lt; 30 mL/min.</p>
            </list-item>
            <list-item>
              <p>MAPA e MRPA, quando necess&#225;rio para investiga&#231;&#227;o da HAS do avental branco, HAS mascarada, em casos em que for necess&#225;rio investigar epis&#243;dios de hipotens&#227;o arterial ou mesmo para avalia&#231;&#227;o da efic&#225;cia terap&#234;utica da HAS.<xref ref-type="bibr" rid="B193"><sup>193</sup></xref></p>
            </list-item>
          </list>
        </sec>
      </sec>
      <sec>
        <title>5.2. Peculiaridades no Tratamento</title>
        <sec>
          <title>5.2.1. Metas Terap&#234;uticas no Idoso</title>
          <p>O tratamento da HAS no paciente idoso representa um grande desafio, uma vez que se trata de um grupo heterog&#234;neo, com m&#250;ltiplas comorbidades, problemas cognitivos, risco de queda, polifarm&#225;cia e s&#237;ndrome da fragilidade. Portanto, no idoso, as metas terap&#234;uticas devem ser individualizadas, baseadas no julgamento da equipe multidisciplinar e considerar suas prefer&#234;ncias.<xref ref-type="bibr" rid="B193"><sup>193</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B194"><sup>194</sup></xref> Os ajustes de dose devem ser realizados a cada 4 semanas, para evitar redu&#231;&#245;es abruptas de PA. O estudo <italic>Hypertension in the Very Elderly Trial</italic> (HYVET),<xref ref-type="bibr" rid="B194"><sup>194</sup></xref> randomizado controlado com placebo, incluiu 3.845 pacientes com mais de 80 anos, idade m&#233;dia de 83,6 anos, com HAS &#8805; 160 mmHg. A meta press&#243;rica utilizada foi 150/80 mmHg. Demonstrou que o tratamento com indapamida, com ou sem perindopril, foi ben&#233;fico em octogen&#225;rios. Na an&#225;lise baseada em inten&#231;&#227;o de tratar, ocorreu redu&#231;&#227;o de 30% na taxa de AVE fatal ou n&#227;o fatal, de 39% na taxa de morte por AVE, de 21% de morte por qualquer causa, de 23% de morte por causa cardiovascular e de 64% de IC. Poucos eventos adversos graves ocorreram no grupo de tratamento ativo (358 versus 448 no grupo placebo). Existem evid&#234;ncias de que baixar muito a PA em idosos pode ser prejudicial, fato este conhecido como curva em J ou em U.<xref ref-type="bibr" rid="B191"><sup>191</sup></xref> Estudo recente, o SPRINT,<xref ref-type="bibr" rid="B149"><sup>149</sup></xref> procurou avaliar duas metas diferentes de PA. No grupo padr&#227;o, a meta era PAS &lt; 140 mmHg e, no grupo tratamento intensivo, a meta era PA sist&#243;lica &lt; 120 mmHg. O grupo tratamento intensivo apresentou redu&#231;&#227;o significativa de eventos prim&#225;rios (infarto, outras s&#237;ndromes coronarianas agudas, AVE, IC ou morte por causas cardiovasculares) quando comparado com o grupo tratamento padr&#227;o. Embora a impress&#227;o inicial seja a de que metas mais rigorosas podem ser mais ben&#233;ficas, h&#225; de se levar em considera&#231;&#227;o que houve aumento no n&#250;mero de eventos adversos graves, como hipotens&#227;o, s&#237;ncope, dist&#250;rbios eletrol&#237;ticos e insufici&#234;ncia renal aguda, no grupo tratamento intensivo. Outro estudo importante foi o ACCORD.<xref ref-type="bibr" rid="B35"><sup>35</sup></xref> Realizado em 10.251 diab&#233;ticos, de 40 a 79 anos de idade, sendo que 4.733 diab&#233;ticos foram tamb&#233;m randomizados para redu&#231;&#227;o de PA &lt; 140 mmHg ou &lt; 120 mmHg. Entretanto, a redu&#231;&#227;o de PA a metas mais intensas n&#227;o conseguiu reduzir significativamente o risco de desfecho prim&#225;rio do estudo (morte por doen&#231;a cardiovascular, infarto n&#227;o fatal, AVE n&#227;o fatal). Assim, at&#233; o momento, a recomenda&#231;&#227;o das III Diretrizes em Cardiogeriatria, para o idoso &#8805; 65 anos de idade, sem crit&#233;rios de fragilidade, considerado um idoso robusto, s&#227;o de n&#237;veis de PAS &#8804; 130 mmHg<xref ref-type="bibr" rid="B195"><sup>195</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B196"><sup>196</sup></xref> Para o paciente &#8804; 80 anos de idade, sem fragilidade, pode-se considerar n&#237;veis press&#243;ricos de PAS &lt; 140 mmHg;<xref ref-type="bibr" rid="B195"><sup>195</sup></xref> nos pacientes &#8805; 80 anos e PAS &#8805; 160 mmHg, pode-se admitir uma redu&#231;&#227;o inicial da PAS entre 150 e 140 mmHg;<xref ref-type="bibr" rid="B7"><sup>7</sup></xref> no idoso fr&#225;gil ou com m&#250;ltiplas comorbidades, a meta terap&#234;utica deve ser individualizada e consideradas as rela&#231;&#245;es riscos/benef&#237;cios em cada caso.<xref ref-type="bibr" rid="B196"><sup>196</sup></xref></p>
        </sec>
        <sec>
          <title>5.2.2. Tratamentos N&#227;o Medicamentoso e Medicamentoso</title>
          <p>A redu&#231;&#227;o do sal deve ser criteriosa e bem acompanhada pelo m&#233;dico, pois a diminui&#231;&#227;o da sensibilidade gustativa do idoso pode fazer com que o alimento se torne menos saboroso, e o idoso passe a comer pouco, com risco de desnutri&#231;&#227;o. Deve-se tamb&#233;m lembrar que o idoso raramente apresenta apenas uma doen&#231;a cr&#244;nica. A avalia&#231;&#227;o das multimorbidades geralmente define o melhor tratamento e qual o f&#225;rmaco a ser evitado naquele idoso espec&#237;fico. O tratamento deve ser iniciado com baixas doses e o ajuste deve ser gradativo. A ades&#227;o deve ser estimulada, se poss&#237;vel, por controle mensal no in&#237;cio do tratamento e a cada ajuste de dose. Os f&#225;rmacos mais comumente utilizados no idoso s&#227;o:</p>
          <list list-type="alpha-lower">
            <list-item>
              <p>Diur&#233;ticos: os tiaz&#237;dicos e correlatos (hidroclorotiazida, clortalidona, indapamida) s&#227;o considerados f&#225;rmacos de primeira linha em idosos sem comorbidades. Apresentam uso preferencial em idoso com osteoporose, pois diminuem a excre&#231;&#227;o urin&#225;ria de c&#225;lcio, e em fases iniciais da insufici&#234;ncia card&#237;aca congestiva (ICC), por reduzirem pr&#233;-carga, volume e congest&#227;o pulmonar. Doses recomendadas de hidroclorotiazida: 6,25 mg a 25 mg/dia, em que a efic&#225;cia &#233; mantida e os efeitos metab&#243;licos adversos s&#227;o reduzidos.<xref ref-type="bibr" rid="B191"><sup>191</sup></xref> Na maioria dos casos, os diur&#233;ticos s&#227;o associados ao esquema terap&#234;utico. Entretanto, devem ser evitados em idosos com incontin&#234;ncia urin&#225;ria incipiente, gota (elevam o &#225;cido &#250;rico) e prostatismo.<xref ref-type="bibr" rid="B191"><sup>191</sup></xref> Deve-se ter aten&#231;&#227;o &#224; glicemia em idosos com uso concomitante de tiaz&#237;dicos e antidiab&#233;ticos orais ou insulina, pois os tiaz&#237;dicos podem aumentar a glicemia e prejudicar o controle do diab&#233;tico.&#160;</p>
            </list-item>
            <list-item>
              <p>Antagonistas de canal de c&#225;lcio: compreendem os di-hidropirid&#237;nicos e os n&#227;o di-hidropiridinicos. Os di-hidropirid&#237;nicos t&#234;m grande efeito vasodilatador e os de &#250;ltima gera&#231;&#227;o provocam menos edema. S&#227;o muito utilizados em idosos com HAS e doen&#231;a coronariana sintom&#225;tica. J&#225; os n&#227;o di-hidropiridinicos, em especial o verapamil, t&#234;m menor efeito vasodilatador e n&#227;o costumam ser prescritos para idosos, pois podem alterar a condu&#231;&#227;o atrioventricular do impulso el&#233;trico. Verapamil pode ainda provocar obstipa&#231;&#227;o intestinal.</p>
            </list-item>
            <list-item>
              <p>IECA: mant&#234;m efic&#225;cia em idosos, apesar da diminui&#231;&#227;o da renina com o envelhecimento. Diminuem eventos cardiovasculares e devem ser utilizados em idosos com HAS e IC ou disfun&#231;&#227;o ventricular assintom&#225;tica. Como efeitos adversos, encontram-se a altera&#231;&#227;o do paladar, especialmente com o captopril, que pode reduzir a ingest&#227;o de alimentos, e tosse seca, que limitam seu uso. &#201; fundamental o controle de pot&#225;ssio devido &#224; fun&#231;&#227;o renal frequentemente reduzida.</p>
            </list-item>
            <list-item>
              <p>Antagonistas de receptor de angiotensina II (ARA II): s&#227;o eficazes na IC e apresentam a&#231;&#227;o protetora renal e card&#237;aca no diab&#233;tico tipo 2 com nefropatia estabelecida.<xref ref-type="bibr" rid="B191"><sup>191</sup></xref> Os ARA II apresentam bom perfil de tolerabilidade, com poucos efeitos adversos (tontura ocasional e, raramente, rea&#231;&#227;o de hipersensibilidade cut&#226;nea). Bem utilizados quando existe intoler&#226;ncia aos IECA.<xref ref-type="bibr" rid="B193"><sup>193</sup></xref></p>
            </list-item>
            <list-item>
              <p>Betabloqueador: n&#227;o &#233; usado como monoterapia inicial em idosos sem comorbidades por seu menor efeito em redu&#231;&#227;o de PA, por&#233;m, em associa&#231;&#227;o com diur&#233;tico, apresenta bom resultado. &#201; utilizado principalmente em idoso com HAS e insufici&#234;ncia coronariana ou IC. Os betabloqueadores menos lipossol&#250;veis, como atenolol, metoprolol e bisoprolol, s&#227;o os recomendados em idosos por seu menor risco de efeito colateral no sistema nervoso central (depress&#227;o, sonol&#234;ncia, confus&#227;o, dist&#250;rbio do sono).<xref ref-type="bibr" rid="B193"><sup>193</sup></xref></p>
            </list-item>
          </list>
          <p>Em resumo, o idoso tem particularidades no diagn&#243;stico e abordagem da HAS, em que devem ser consideradas as comorbidades e as particularidades de cada um, inclusive estado funcional, que podem ser determinantes nas metas da PA a serem alcan&#231;adas e na tomada de decis&#227;o para o idoso.</p>
          <table-wrap id="t27">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="middle">Recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">Grau de recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">PAS &#8804; 130 mmHg para o idoso &#8805; 65 anos, sem fragilidade</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top">PAS &lt; 140 mmHg para o idoso &#8804; 80 anos, sem fragilidade</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">No idoso &gt; 80 anos e PAS inicial &#8805; 160 mmHg, redu&#231;&#227;o inicial da PAS entre 150 e 140 mmHg</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">No idoso fr&#225;gil ou com m&#250;ltiplas comorbidades, a meta terap&#234;utica deve ser individualizada e consideradas as rela&#231;&#245;es riscos/benef&#237;cios</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN12a">
                <p><italic>PAS: press&#227;o arterial sist&#234;mica</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
      </sec>
    </sec>
    <sec>
      <title>6. Valvopatias</title>
      <sec>
        <title>6.1. Estenose Mitral</title>
        <sec>
          <title>6.1.1. Peculiaridades no Diagn&#243;stico</title>
          <p>A estenose mitral (EM) &#233; rara entre os idosos (presente em 6% dos portadores de calcifica&#231;&#227;o do anel mitral).<xref ref-type="bibr" rid="B197"><sup>197</sup></xref></p>
          <p>Etiologia &#8211; Sequela de cardite reum&#225;tica ou calcifica&#231;&#227;o do aparelho valvar mitral. H&#225; relatos de cardite reum&#225;tica em pacientes &gt; 85 anos de idade.<xref ref-type="bibr" rid="B198"><sup>198</sup></xref></p>
          <p>Sintomas &#8211; Semelhantes aos observados em n&#227;o idosos e podem estar ausentes. Os mais frequentes s&#227;o dispneia e tosse, podendo ser acompanhadas de expectora&#231;&#227;o hemoptoica. Pode manifestar-se como embolia sist&#234;mica ou FA.</p>
          <p>Exame f&#237;sico &#8211; Hiperfonese da primeira bulha e sopro mesodiast&#243;lico apical com fr&#234;mito podem estar ausentes. Estalido de abertura da valva mitral raramente &#233; auscultado. A maioria dos pacientes &gt; 80 anos de idade apresenta FA com elevada FC que, associada a maior di&#226;metro anteroposterior do t&#243;rax, dificulta a ausculta. Quanto mais fibrosada e calcificada a valva mitral, menos aud&#237;veis ser&#227;o os sinais auscultat&#243;rios da EM, cuja suspeita diagn&#243;stica pode ser estabelecida a partir dos sinais de hipertens&#227;o arterial pulmonar (hiperfonese de P2 na segunda bulha card&#237;aca, insufici&#234;ncia ventricular direita, regurgita&#231;&#227;o pulmonar e tric&#250;spide). Nos idosos com hipertens&#227;o arterial pulmonar sem outra causa evidente, &#233; importante investigar EM.<xref ref-type="bibr" rid="B199"><sup>199</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B202"><sup>202</sup></xref></p>
          <p>Exames complementares &#8211; ECG, radiografia do t&#243;rax e ecocardiograma s&#227;o suficientes, na maioria dos casos, para confirmar o diagn&#243;stico e estimar a gravidade. Ao ECG podem ser encontradas: sobrecarga atrial esquerda (SAE), hipertrofia ventricular direita e FA. Na radiografia do t&#243;rax: aumento do AE, calcifica&#231;&#227;o da valva mitral e deslocamento posterior do es&#244;fago contendo b&#225;rio. Dados ecocardiogr&#225;ficos: calcifica&#231;&#227;o do anel mitral (em 60% dos idosos &gt; 85 anos de idade),<xref ref-type="bibr" rid="B4"><sup>4</sup></xref> avalia&#231;&#227;o da &#225;rea (<xref ref-type="table" rid="t28">Tabela 8</xref>), da PA pulmonar e do estado do aparelho valvar (mobilidade, espessamento e acometimento subvalvar).<xref ref-type="bibr" rid="B5"><sup>5</sup></xref></p>
          <table-wrap id="t28">
            <label>Tabela 8</label>
            <caption>
              <title>Gravidade da estenose mitral</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="center" valign="top"/>
                  <th align="center" valign="top">Gradiente press&#243;rico (AE-VE) em mmHg</th>
                  <th align="center" valign="top">&#193;rea valvar mitral (cm&#178;)</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Leve</td>
                  <td align="center" valign="top">&lt; 5</td>
                  <td align="center" valign="top">&gt; 1,5</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Moderada</td>
                  <td align="center" valign="top">5 a 10</td>
                  <td align="center" valign="top">1 a 1,5</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Grave</td>
                  <td align="center" valign="top">&gt; 10</td>
                  <td align="center" valign="top">&lt; 1</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN8">
                <p>
                  <italic>AE: &#225;trio esquerdo. VE: ventr&#237;culo esquerdo.</italic>
                  <xref ref-type="bibr" rid="B202">
                    <sup>202</sup>
                  </xref>
                </p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>6.1.2. Peculiaridades no Tratamento</title>
          <p>Tratamento cl&#237;nico &#8211; Os portadores de EM leve geralmente s&#227;o assintom&#225;ticos e n&#227;o necessitar&#227;o receber medica&#231;&#227;o,<xref ref-type="bibr" rid="B203"><sup>203</sup></xref> exceto se forem portadores de FA. Diferentemente dos pacientes jovens, os idosos portadores de EM que desenvolvem FA t&#234;m maior chance de apresentarem sintomas de IC, pela presen&#231;a de disfun&#231;&#227;o diast&#243;lica concomitante. Assim, no caso de FA parox&#237;stica com piora hemodin&#226;mica, mesmo se a EM for leve, est&#225; indicada a cardiovers&#227;o el&#233;trica. Os portadores de FA e EM, seja ela permanente, persistente ou parox&#237;stica, devem fazer uso constante de varfarina, independente da pontua&#231;&#227;o em escores de risco, visando manter a rela&#231;&#227;o normatizada internacional (INR) entre 2 e 3, a menos que exista contraindica&#231;&#227;o formal.<xref ref-type="bibr" rid="B204"><sup>204</sup></xref> Embora algumas publica&#231;&#245;es recomendem o uso dos novos anticoagulantes orais nesta situa&#231;&#227;o, este dado ainda n&#227;o foi avaliado em estudos comparativos.<xref ref-type="bibr" rid="B205"><sup>205</sup></xref> O achado de trombo atrial esquerdo ou o surgimento de um evento emb&#243;lico sist&#234;mico, mesmo na presen&#231;a de ritmo sinusal (RS), tamb&#233;m indicam o uso da anticoagula&#231;&#227;o. Na EM de etiologia reum&#225;tica, n&#227;o &#233; necess&#225;ria a profilaxia para febre reum&#225;tica, visto que a recidiva desta doen&#231;a &#233; rara em idosos.<xref ref-type="bibr" rid="B206"><sup>206</sup></xref> Recomenda-se o tratamento precoce de infec&#231;&#245;es bacterianas, visando proteger o paciente do risco de endocardite infecciosa (EI). N&#227;o est&#225; indicada a quimioprofilaxia para EI na EM nos idosos.<xref ref-type="bibr" rid="B207"><sup>207</sup></xref> Nos pacientes sintom&#225;ticos, portadores de EM moderada a importante, os diur&#233;ticos de al&#231;a s&#227;o a melhor op&#231;&#227;o para o controle da congest&#227;o pulmonar ou sist&#234;mica, e os betabloqueadores est&#227;o indicados para reduzir a FC e facilitar o esvaziamento atrial. N&#227;o existem evid&#234;ncias do benef&#237;cio do uso de betabloqueadores em pacientes em RS que n&#227;o estejam com FC elevada.<xref ref-type="bibr" rid="B208"><sup>208</sup></xref> Na presen&#231;a de FA com resposta ventricular elevada, os betabloqueadores s&#227;o os f&#225;rmacos de escolha para redu&#231;&#227;o da FC. Em caso de contraindica&#231;&#227;o, pode-se usar bloqueadores de canais de c&#225;lcio n&#227;o di-hidropirid&#237;nicos ou digital. Na presen&#231;a de sinais de fal&#234;ncia ventricular direita com hepatomegalia associada, devido &#224; frequente coexist&#234;ncia de hiperaldosteronismo secund&#225;rio, a utiliza&#231;&#227;o de espironolactona em doses elevadas (100 mg/dia) &#233; uma op&#231;&#227;o.<xref ref-type="bibr" rid="B209"><sup>209</sup></xref> Deve-se ter cautela com risco de hipercalemia.</p>
          <p>Op&#231;&#245;es para corre&#231;&#227;o da EM &#8211; Ao avaliarmos um idoso portador de EM com indica&#231;&#227;o para interven&#231;&#227;o. Al&#233;m da etiologia, se reum&#225;tica ou degenerativa, a expectativa de vida do paciente, a avalia&#231;&#227;o da funcionalidade e a presen&#231;a de multimorbidades devem ser consideradas e discutidas com o paciente e/ou familiares. Para corrigirmos a EM reum&#225;tica temos duas op&#231;&#245;es: a valvoplastia mitral percut&#226;nea por cateter-bal&#227;o (VMPCB) ou a cirurgia com circula&#231;&#227;o extracorp&#243;rea. Ensaios cl&#237;nicos randomizados mostram que, em casos selecionados, a VMPCB oferece resultados imediatos e a longo prazo similares aos da comissurotomia cir&#250;rgica aberta.<xref ref-type="bibr" rid="B210"><sup>210</sup></xref> Para isto, &#233; importante a presen&#231;a de morfologia valvar favor&#225;vel, avaliada por meio de v&#225;rios crit&#233;rios ecocardiogr&#225;ficos propostos, sendo os crit&#233;rios de Wilkins e Block os mais utilizados.<xref ref-type="bibr" rid="B211"><sup>211</sup></xref> Al&#233;m disto, devem ser respeitadas as contraindica&#231;&#245;es ao procedimento (presen&#231;a de trombo em AE ou regurgita&#231;&#227;o mitral de grau maior que leve). Infelizmente, os pacientes idosos frequentemente apresentam morfologia valvar desfavor&#225;vel a este procedimento, seja de etiologia reum&#225;tica ou degenerativa.<xref ref-type="bibr" rid="B212"><sup>212</sup></xref> Neste &#250;ltimo caso, pelo fato de n&#227;o haver fus&#227;o comissural como ocorre na doen&#231;a reum&#225;tica, o sucesso da VMPCB fica restrito, sendo a cirurgia para troca valvar mitral o procedimento de escolha. Como os portadores de EM degenerativa frequentemente apresentam multimorbidades que elevam muito seu risco, deve-se tentar o tratamento cl&#237;nico inicialmente, estando a troca valvar indicada apenas em casos n&#227;o responsivos ao mesmo.<xref ref-type="bibr" rid="B213"><sup>213</sup></xref> Existem relatos de pequenas s&#233;ries de implante percut&#226;neo de pr&#243;tese mitral na EM degenerativa, com sucesso relativo.<xref ref-type="bibr" rid="B214"><sup>214</sup></xref></p>
          <table-wrap id="t29">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top" colspan="3">Tratamento medicamentoso nos idosos com estenose mitral</th>
                </tr>
                <tr>
                  <th align="left" valign="middle">Recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">Grau de recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Portadores de EM independente da gravidade que apresentem FA seja ela parox&#237;stica, persistente ou permanente devem receber varfarina indefinidamente, visando manter INR entre 2 e 3, a menos que haja contraindica&#231;&#227;o &#224; mesma</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Portadores de EM com indica&#231;&#227;o para uso de varfarina podem fazer uso dos novos anticoagulantes orais</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Idosos portadores de EM reum&#225;tica devem fazer profilaxia para febre reum&#225;tica</td>
                  <td align="center" valign="top">III</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Idosos com EM com AVM menor ou igual a 1,5 cm<sup>2</sup>, em CF II, III ou IV e/ou sinais de IVD devem receber diur&#233;ticos de al&#231;a para al&#237;vio dos sintomas</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Idosos com EM com AVM menor ou igual a 1,5 cm2, em CF II, III ou IV, em RS, que persistem sintom&#225;ticos apesar do uso de diur&#233;ticos, se FC acima de 60 bpm, devem receber betabloqueadores, a menos que haja contraindica&#231;&#227;o</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Idosos portadores de EM mesmo leve que desenvolvam FA com resposta ventricular elevada devem receber betabloqueador para controle da resposta ventricular, a menos que haja contraindica&#231;&#227;o</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Nos casos acima citados, pode-se utilizar bloqueadores dos canais de c&#225;lcio n&#227;o di-hidropirid&#237;nicos ou digital, em caso de contraindica&#231;&#227;o aos betabloqueadores</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Portadores de EM com sinais de IVD e hepatomegalia, sem resposta adequada a diur&#233;ticos de al&#231;a, devem receber espironolactona.</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN13a">
                <p><italic>AVM: &#225;rea valvar mitral; bpm: batimentos por minuto; CF: classe funcional da New York Heart Association; EM: estenose mitral; FA: fibrila&#231;&#227;o atrial; FC: frequ&#234;ncia card&#237;aca; INR: rela&#231;&#227;o normatizada internacional; IVD: insufici&#234;ncia ventricular direita; RS: ritmo sinusal</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <table-wrap id="t30">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top" colspan="3">Indica&#231;&#245;es para interven&#231;&#227;o em idosos com estenose mitral reum&#225;tica</th>
                </tr>
                <tr>
                  <th align="left" valign="middle">Recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">Grau de recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Idosos portadores de EM reum&#225;tica sintom&#225;tica (CF II-IV), com AVM &#8804; 1,5 cm2, que apresentem morfologia valvar favor&#225;vel e n&#227;o apresentem contraindica&#231;&#227;o &#224; VMPCB, devem submeter-se &#224; mesma</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Portadores de EM reum&#225;tica que, embora sejam muito sintom&#225;ticos (CF III/IV) com AVM &#8804; 1,5 cm2, mas com morfologia valvar desfavor&#225;vel ou contraindica&#231;&#227;o &#224; VMPCB, sem elevado risco cir&#250;rgico ou baixa expectativa de vida, devem ser encaminhados &#224; cirurgia aberta para realizar valvoplastia ou troca valvar</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Pacientes com EM reum&#225;tica em CF II, AVM &#8804; 1,5 cm<sup>2</sup>, por&#233;m n&#227;o candidatos &#224; VMPCB, &#233; prudente mant&#234;-los em tratamento medicamentoso at&#233; que se tornem mais sintom&#225;ticos</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Portadores de EM reum&#225;tica com AVM &#8804; 1,5 cm<sup>2</sup>, com indica&#231;&#227;o para TVAO, cirurgia de aorta ascendente ou CRVM, tamb&#233;m dever&#227;o realizar valvoplastia ou troca valvar mitral</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Est&#225; indicada a VMPCB em portadores de EM reum&#225;tica, com AVM &#8804;1,5 cm<sup>2</sup>, mesmo que assintom&#225;ticos, por&#233;m que sejam portadores de hipertens&#227;o arterial pulmonar (PSAP &gt; 50 mmHg), cuja prov&#225;vel etiologia seja a EM, quando a morfologia valvar for favor&#225;vel, na aus&#234;ncia de contraindica&#231;&#227;o</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Portadores de EM reum&#225;tica grave (AVM &#8804; 1,0 cm<sup>2</sup>), assintom&#225;ticos, com morfologia valvar favor&#225;vel &#224; VMPCB, sem contraindica&#231;&#227;o &#224; mesma, devem realizar o procedimento</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN14a">
                <p><italic>AVM: &#225;rea valvar mitral; CF: classe funcional da New York Heart Association; CRVM: cirugia de revasculariza&#231;&#227;o do mioc&#225;rdio; EM: estenose mitral; PSAP: press&#227;o sist&#243;lica em art&#233;ria pulmonar; TVAO: troca de valva a&#243;rtica; VMPCB: valvoplastia mitral percut&#226;nea por cateter-bal&#227;o</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <table-wrap id="t31">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top" colspan="3">Indica&#231;&#245;es para interven&#231;&#227;o em idosos com estenose mitral degenerativa</th>
                </tr>
                <tr>
                  <th align="left" valign="middle">Recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">Grau de recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">TVM para idosos portadores de EM degenerativa sem resposta adequada ao tratamento cl&#237;nico, com baixo risco cir&#250;rgico e expectativa de vida elevada</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">VMPCB para portadores de EM degenerativa CF III/IV, sem resposta ao tratamento cl&#237;nico, com elevado risco cir&#250;rgico</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Implante percut&#226;neo de pr&#243;tese mitral para pacientes muito sintom&#225;ticos, sem resposta ao tratamento cl&#237;nico e n&#227;o candidatos a cirurgia aberta ou VMPCB</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN15a">
                <p><italic>CF: classe funcional da New York Heart Association; EM: estenose mitral; TVM: troca valvar mitral; VMPCB: valvuloplastia mitral percut&#226;nea por cateter-bal&#227;o</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
      </sec>
      <sec>
        <title>6.2. Insufici&#234;ncia Mitral</title>
        <sec>
          <title>6.2.1. Peculiaridades no Diagn&#243;stico</title>
          <p>Do ponto de vista etiol&#243;gico, a insufici&#234;ncia mitral (IM) pode ser: (a) prim&#225;ria: quando h&#225; altera&#231;&#227;o histol&#243;gica na valva, por exemplo, degenera&#231;&#227;o mixomatosa, doen&#231;a fibroel&#225;stica degenerativa, doen&#231;a reum&#225;tica, EI; ou (b) secund&#225;ria: quando a IM &#233; funcional e a valva &#233; histologicamente normal, por exemplo, IM por m&#225; coapta&#231;&#227;o dos folhetos na miocardiopatia dilatada. A IM &#233; comum em idosos, sendo a causa degenerativa a mais frequente, seguida da isqu&#234;mica e, menos frequentemente, por doen&#231;a reum&#225;tica e EI.<xref ref-type="bibr" rid="B215"><sup>215</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B216"><sup>216</sup></xref> A IM aguda est&#225; ligada principalmente &#224; DAC por disfun&#231;&#227;o do m&#250;sculo papilar ou rotura da cordoalha tend&#237;nea, com um quadro de IC aguda.</p>
          <p>Sintomas &#8211; A sintomatologia na IM cr&#244;nica est&#225; relacionada a gravidade, taxa de progress&#227;o da doen&#231;a, PA pulmonar, presen&#231;a de arritmias (p. ex., FA) e doen&#231;as associadas. Os sintomas mais comuns s&#227;o a dispneia de esfor&#231;o e a fadiga.</p>
          <p>Exame f&#237;sico &#8211; Apresenta sopro protossist&#243;lico em foco mitral, intensidade vari&#225;vel e &#237;ctus deslocado, com caracter&#237;sticas de sobrecarga volum&#233;trica. Deformidades tor&#225;cicas, comuns nessa idade, como cifose ou cifoescoliose, podem modificar &#237;ctus, bulhas e sopros.<xref ref-type="bibr" rid="B102"><sup>102</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B202"><sup>202</sup></xref></p>
          <p>Exames complementares &#8211; Ao ECG as anormalidades frequentes s&#227;o a SAE, FA e sobrecarga ventricular esquerda (SVE).<xref ref-type="bibr" rid="B217"><sup>217</sup></xref> Na presen&#231;a de IM isqu&#234;mica, podem-se encontrar sinais eletrocardiogr&#225;ficos de insufici&#234;ncia coron&#225;ria, como zonas eletricamente inativas e altera&#231;&#245;es da repolariza&#231;&#227;o ventricular.<xref ref-type="bibr" rid="B218"><sup>218</sup></xref> Na IM aguda o ECG pode ser normal, ou mostrar apenas taquicardia sinusal.<xref ref-type="bibr" rid="B217"><sup>217</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B219"><sup>219</sup></xref> A radiografia de t&#243;rax auxilia na detec&#231;&#227;o de comorbidades, na avalia&#231;&#227;o de congest&#227;o pulmonar e na distin&#231;&#227;o entre casos agudos e cr&#244;nicos. Na IM aguda, o cora&#231;&#227;o pode ter dimens&#245;es normais, por&#233;m existe congest&#227;o pulmonar. Na IM cr&#244;nica haver&#225; aumento do &#225;trio e ventr&#237;culo esquerdos.<xref ref-type="bibr" rid="B217"><sup>217</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B218"><sup>218</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B220"><sup>220</sup></xref> O ecocardiograma transtor&#225;cico &#233; indispens&#225;vel para diagn&#243;stico e avalia&#231;&#227;o do grau de regurgita&#231;&#227;o mitral, tamanho das c&#226;maras e fun&#231;&#227;o ventricular. De especial import&#226;ncia s&#227;o as dimens&#245;es do &#225;trio e ventr&#237;culo esquerdos e a medida da press&#227;o da art&#233;ria pulmonar. Identifica&#231;&#227;o da causa e avalia&#231;&#227;o detalhada do comprometimento do aparelho valvar, morfologia dos folhetos e mecanismo do refluxo s&#227;o importantes para decidir o tratamento mais adequado, se troca ou plastia da valva mitral.<xref ref-type="bibr" rid="B202"><sup>202</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B221"><sup>221</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B222"><sup>222</sup></xref> O ecocardiografia transesof&#225;gico (ETE)pode ser utilizado quando existirem dificuldades t&#233;cnicas de adequa&#231;&#227;o da janela ecocardiogr&#225;fica. O cateterismo card&#237;aco est&#225; indicado para diagn&#243;stico de DAC nos pacientes encaminhados &#224; cirurgia e em casos de d&#250;vidas na gravidade da les&#227;o.<xref ref-type="bibr" rid="B102"><sup>102</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B202"><sup>202</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B221"><sup>221</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B222"><sup>222</sup></xref> Os TE/ergoespirom&#233;trico podem ser usados para avaliar a reprodu&#231;&#227;o de sintomas e as mudan&#231;as na toler&#226;ncia ao exerc&#237;cio. S&#227;o menos utilizados entre os muito idosos com limita&#231;&#245;es f&#237;sicas.<xref ref-type="bibr" rid="B202"><sup>202</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B217"><sup>217</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B221"><sup>221</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B222"><sup>222</sup></xref> A resson&#226;ncia magn&#233;tica e a tomografia computadorizada n&#227;o s&#227;o utilizadas de rotina nos pacientes com doen&#231;a mitral, mas podem ser indicadas quando a gravidade da IM ou a fun&#231;&#227;o ventricular esquerda n&#227;o forem adequadamente avaliadas pelo ecocardiograma ou forem discrepantes.<xref ref-type="bibr" rid="B221"><sup>221</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B222"><sup>222</sup></xref></p>
        </sec>
        <sec>
          <title>6.2.2. Peculiaridades no Tratamento</title>
          <p>O tratamento da IM deve considerar sua etiologia e a gravidade. A presen&#231;a de FA, hipertens&#227;o pulmonar e sintomas &#233; fator relevante no processo de tomada de decis&#227;o. Idosos &gt; 75 anos de idade apresentam risco cir&#250;rgico elevado. O manejo cir&#250;rgico nesta faixa et&#225;ria visa &#224; melhora e &#224; manuten&#231;&#227;o da qualidade de vida. Portanto, a presen&#231;a de sintomas &#233; fator determinante na indica&#231;&#227;o cir&#250;rgica. Pacientes com disfun&#231;&#227;o ventricular, por&#233;m assintom&#225;ticos, s&#227;o mantidos em tratamento cl&#237;nico.<xref ref-type="bibr" rid="B221"><sup>221</sup></xref> A decis&#227;o terap&#234;utica da IM deve ser norteada pela sua apresenta&#231;&#227;o (aguda ou cr&#244;nica), pelo perfil cl&#237;nico hemodin&#226;mico e pela gravidade dos sintomas. Os par&#226;metros ecocardiogr&#225;ficos, como a FEVE, o di&#226;metro sist&#243;lico final de ventr&#237;culo esquerdo (DSFVE) e a presen&#231;a de dispneia s&#227;o indicativos de terapia cir&#250;rgica (Ver quadro de recomenda&#231;&#227;o a seguir). A plastia mitral &#233; o tratamento cir&#250;rgico preferencial. Atualmente o clip mitral &#233; uma alternativa incipiente e promissora.<xref ref-type="bibr" rid="B221"><sup>221</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B223"><sup>223</sup></xref></p>
          <p>Tratamento da IM aguda &#8211; Nos pacientes com IM aguda e grave est&#225; recomendado o tratamento cir&#250;rgico imediato. Alguns pacientes com IM moderada podem desenvolver compensa&#231;&#227;o hemodin&#226;mica devido &#224; dilata&#231;&#227;o do VE, possibilitando uma press&#227;o de enchimento menor e normaliza&#231;&#227;o do d&#233;bito card&#237;aco. Nos casos de rotura de cordoalha tend&#237;nea, reparo mitral &#233; preferido &#224; troca valvar e o momento da cirurgia pode ser definido pelo estado cl&#237;nico e hemodin&#226;mico do paciente.<xref ref-type="bibr" rid="B221"><sup>221</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B223"><sup>223</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B224"><sup>224</sup></xref> O tratamento medicamentoso na IM aguda deve ser institu&#237;do como terapia de suporte para o procedimento cir&#250;rgico da corre&#231;&#227;o definitiva.<xref ref-type="bibr" rid="B221"><sup>221</sup></xref> Na presen&#231;a de quadros graves, como edema agudo de pulm&#227;o ou choque, h&#225; indica&#231;&#227;o de f&#225;rmacos vasoativos, como vasodilatadores intravenosos, nitroprussiato de s&#243;dio, nitroglicerina, aminas vasopressoras e bal&#227;o intra-a&#243;rtico para suporte hemodin&#226;mico at&#233; o procedimento cir&#250;rgico indicado.<xref ref-type="bibr" rid="B223"><sup>223</sup></xref></p>
          <p>Tratamento da IM cr&#244;nica &#8211; Pacientes com IM cr&#244;nica e assintom&#225;ticos, com FEVE normal, n&#227;o apresentam indica&#231;&#227;o de tratamento medicamentoso. N&#227;o h&#225; evid&#234;ncia de que o tratamento com vasodilatadores a longo prazo apresente benef&#237;cios terap&#234;uticos.<xref ref-type="bibr" rid="B221"><sup>221</sup></xref> Nos sintom&#225;ticos, o tratamento deve ser institu&#237;do com IECA, betabetabloqueadores, como carvedilol, e diur&#233;ticos.<xref ref-type="bibr" rid="B224"><sup>224</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B225"><sup>225</sup></xref> O MP biventricular nos pacientes classificados como &#8220;respondedores&#8221; apresenta melhora da IM pela geometria reversa de VE.<xref ref-type="bibr" rid="B226"><sup>226</sup></xref> Pacientes com IM cr&#244;nica prim&#225;ria sintom&#225;ticos dever&#227;o ser submetidos ao tratamento cir&#250;rgico, preferencialmente plastia, independentemente da fun&#231;&#227;o ventricular esquerda. Pacientes assintom&#225;ticos, mas que apresentem progressiva disfun&#231;&#227;o (FEVE &lt; 0,60) e/ou aumento dos di&#226;metros ventriculares (DSFVE &gt; 45 mm), tamb&#233;m devem ser considerados para cirurgia. A indica&#231;&#227;o cir&#250;rgica valvar em idosos &gt; 75 anos de idade n&#227;o foi avaliada consistentemente em ensaios cl&#237;nicos, devendo-se priorizar a presen&#231;a de sintomas como indica&#231;&#227;o de interven&#231;&#227;o invasiva. Na cirurgia de troca mitral, as biopr&#243;teses est&#227;o indicadas no idoso por menor taxa de disfun&#231;&#227;o prot&#233;tica e risco inerente &#224; terapia anticoagulante.<xref ref-type="bibr" rid="B227"><sup>227</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B228"><sup>228</sup></xref></p>
          <p>Tratamento da IM por via percut&#226;nea &#8211; O tratamento percut&#226;neo da IM tem sido realizado, especialmente na Europa. No Brasil, o dispositivo MitraClip<italic>&#174;</italic> &#233; o &#250;nico comercialmente dispon&#237;vel e usado em casos selecionados, devido ao alto custo. A utiliza&#231;&#227;o desse dispositivo &#233; indicada para pacientes com IM prim&#225;ria cr&#244;nica de etiologia degenerativa nos quais o risco cir&#250;rgico seja elevado ou proibitivo. Adicionalmente, pacientes com IM cr&#244;nica, secund&#225;ria &#224; dilata&#231;&#227;o ventricular e refrat&#225;rios ao tratamento cl&#237;nico otimizado e &#224; ressincroniza&#231;&#227;o card&#237;aca, podem eventualmente se beneficiar desse procedimento. Em pacientes sintom&#225;ticos com IM grave por degenera&#231;&#227;o de biopr&#243;teses ou an&#233;is valvares previamente implantados e risco cir&#250;rgico proibitivo, a troca mitral percut&#226;nea por interm&#233;dio do procedimento valve-in-valve &#233; uma alternativa em centros especializados. A troca mitral percut&#226;nea para pacientes sintom&#225;ticos com IM grave de valva nativa e risco cir&#250;rgico proibitivo encontra-se em fase avan&#231;ada de desenvolvimento e dever&#225; estar dispon&#237;vel no Brasil nos pr&#243;ximos anos.<xref ref-type="bibr" rid="B229"><sup>229</sup></xref></p>
          <table-wrap id="t32">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top" colspan="3">Recomenda&#231;&#227;o para cirurgia na IM</th>
                </tr>
                <tr>
                  <th align="left" valign="middle">Recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">Grau de recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Pacientes sintom&#225;ticos com IM aguda grave</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Pacientes sintom&#225;ticos com IM prim&#225;ria cr&#244;nica grave e fun&#231;&#227;o ventricular esquerda normal</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Pacientes assintom&#225;ticos com IM prim&#225;ria cr&#244;nica grave e disfun&#231;&#227;o ventricular esquerda (FE 30-60% e ou di&#226;metro sist&#243;lico final &#8805; 40 mm)</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Plastia &#233; prefer&#237;vel &#224; troca mitral em pacientes com IM prim&#225;ria cr&#244;nica grave</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Plastia ou troca mitral &#233; indicada em pacientes com IM prim&#225;ria cr&#244;nica grave em pacientes submetidos &#224; cirurgia card&#237;aca concomitante</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Troca mitral &#233; prefer&#237;vel &#224; plastia em pacientes com IM secund&#225;ria cr&#244;nica de etiologia isqu&#234;mica</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Plastia mitral pode ser considerada para pacientes com IM cr&#244;nica prim&#225;ria (n&#227;o reum&#225;tica) e fun&#231;&#227;o ventricular normal e nova fibrila&#231;&#227;o atrial ou hipertens&#227;o pulmonar (PSAP em repouso &gt; 50 mmHg</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Plastia ou troca mitral pode ser considerada em pacientes sintom&#225;ticos com IM prim&#225;ria cr&#244;nica e FE &#8804; 30%</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Plastia mitral por cateter pode ser considerada em pacientes sintom&#225;ticos (NYHA III/IV) com IM prim&#225;ria cr&#244;nica com risco cir&#250;rgico proibitivo</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Plastia mitral por cateter pode ser considerada em pacientes sintom&#225;ticos (NYHA III/IV) com IM secund&#225;ria (funcional) cr&#244;nica refrat&#225;rios ao tratamento cl&#237;nico e &#224; ressincroniza&#231;&#227;o card&#237;aca</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Pacientes sintom&#225;ticos com IM grave por degenera&#231;&#227;o de biopr&#243;teses ou an&#233;is valvares previamente implantados e risco cir&#250;rgico proibitivo, a troca mitral percut&#226;nea pode ser considerada, em centros especializados</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Pacientes assintom&#225;ticos com IM grave e fun&#231;&#227;o ventricular esquerda preservada (FEVE &gt; 60% e di&#226;metro sist&#243;lico final &lt; 40 mm)</td>
                  <td align="center" valign="top">III</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Plastia ou troca mitral em pacientes com IM moderada submetidos &#224; cirurgia de revasculariza&#231;&#227;o do mioc&#225;rdio concomitante</td>
                  <td align="center" valign="top">III</td>
                  <td align="center" valign="top">A</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN16a">
                <p><italic>FE: fra&#231;&#227;o de eje&#231;&#227;o; FEVE: fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo; IM: insufici&#234;ncia mitral; NYHA: New York Heart Association; PSAP: press&#227;o sist&#243;lica da art&#233;ria pulmonar</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
      </sec>
      <sec>
        <title>6.3. Estenose A&#243;rtica</title>
        <sec>
          <title>6.3.1. Peculiaridades no Diagn&#243;stico</title>
          <p>Para o diagn&#243;stico da EAo, valvopatia mais frequente em idosos, deve-se levar em considera&#231;&#227;o a hist&#243;ria cl&#237;nica, que nessa faixa et&#225;ria pode ser dif&#237;cil por poss&#237;veis altera&#231;&#245;es cognitivas ou sensoriais.</p>
          <p>Sintomas &#8211; O paciente pode ser assintom&#225;tico ou apresentar-se com dispneia, angina de peito ou s&#237;ncope.</p>
          <p>Exame f&#237;sico &#8211; Podemos encontrar: (a) o <italic>ictus cordis</italic> do tipo impulsivo, que em idosos pode estar ausente em virtude do aumento do di&#226;metro anteroposterior da caixa tor&#225;cica; (b) o pulso <italic>parvus et tardus</italic> (amplitude reduzida e tempo de dura&#231;&#227;o prolongado), caracter&#237;stico da EAo nos jovens, pode estar ausente nos idosos, devido ao endurecimento das paredes arteriais que propicia o aumento da VOP, mascarando esse dado semiol&#243;gico; (c) sopro mesossist&#243;lico em crescendo e decrescendo com irradia&#231;&#227;o para o pesco&#231;o e clav&#237;culas. Frequentemente auscultamos o fen&#244;meno de &#8220;Gallavardin&#8221;, que &#233; a irradia&#231;&#227;o do sopro da EAo para a regi&#227;o do &#225;pice; (d) segunda bulha hipofon&#233;tica.</p>
          <p>Exames complementares &#8211; O ECG pode apresentar achados compat&#237;veis com SAE e SVE. A radiografia de t&#243;rax pode apresentar-se normal, em cerca de metade dos idosos examinados, ou com aspecto de hipertrofia, podendo apresentar ou n&#227;o dilata&#231;&#227;o a&#243;rtica p&#243;s-esten&#243;tica. A ecocardiografia &#233; exame fundamental para o diagn&#243;stico e a classifica&#231;&#227;o dessa valvopatia. Utilizam-se mais frequentemente tr&#234;s par&#226;metros ecocardiogr&#225;ficos para classifica&#231;&#227;o de gravidade na EAo: (a) velocidade do jato na raiz da aorta; (b) gradiente m&#233;dio entre o VE e a raiz da aorta; (c) &#225;rea valvar (<xref ref-type="table" rid="t33">Tabela 9</xref>). O TE tem sido indicado nos pacientes assintom&#225;ticos com EAo grave, a fim de verificar a resposta hemodin&#226;mica ao esfor&#231;o; no entanto, seu uso em idosos deve ser individualizado, pela presen&#231;a de multimorbidades que possam impedir o procedimento.</p>
          <table-wrap id="t33">
            <label>Tabela 9</label>
            <caption>
              <title>Diagn&#243;stico e classifica&#231;&#227;o de gravidade das estenoses a&#243;rticas</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup width="25%">
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top">Indicador</th>
                  <th align="center" valign="top">Leve</th>
                  <th align="center" valign="top">Moderada</th>
                  <th align="center" valign="top">Grave</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Velocidade do jato (m/s)</td>
                  <td align="center" valign="top">&lt; 3,0</td>
                  <td align="center" valign="top">3,0 a 4,0</td>
                  <td align="center" valign="top">&gt; 4,0</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Gradiente m&#233;dio (mmHg)</td>
                  <td align="center" valign="top">&lt; 25</td>
                  <td align="center" valign="top">25 a 40</td>
                  <td align="center" valign="top">&gt; 40</td>
                </tr>
                <tr>
                  <td align="left" valign="top">&#193;rea valvar (cm<sup>2</sup>)</td>
                  <td align="center" valign="top">&gt; 1,5</td>
                  <td align="center" valign="top">1,0 a 1,5</td>
                  <td align="center" valign="top">&lt; 1,0</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
        </sec>
        <sec>
          <title>6.3.2. Peculiaridades no Tratamento</title>
          <p>Tratamento medicamentoso &#8211; A HAS &#233; comum no idoso com EAo e contribui para aumento da p&#243;s-carga total, junto &#224; obstru&#231;&#227;o, promovendo sobrecarga do VE. No idoso, deve-se iniciar os antihi-pertensivos com dose baixa e gradualmente titular a posologia. Cautela deve ser tomada com o uso de diur&#233;ticos, devido ao risco de hipotens&#227;o. Os IECA podem ser vantajosos devido &#224; sua a&#231;&#227;o na fibrose ventricular, sendo os betabloqueadores apropriados em pacientes com DAC. O uso de estatinas n&#227;o &#233; indicado para preven&#231;&#227;o da progress&#227;o da EAo.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref> Na presen&#231;a de IC, os betabloqueadores devem ser iniciados com doses baixas e os mesmos cuidados devem ser tomados na prescri&#231;&#227;o de antagonistas da aldosterona, IECA e BRA, e principalmente com o uso de digit&#225;licos, por terem limiar t&#243;xico pr&#243;ximo do terap&#234;utico.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref> Nos idosos &#233; importante a avalia&#231;&#227;o do clearance de creatinina para ajuste da dosagem dos medicamentos, evitando intoxica&#231;&#227;o medicamentosa.</p>
          <p>Tratamento cir&#250;rgico &#8211; A indica&#231;&#227;o da abordagem cir&#250;rgica, tanto a troca valvar a&#243;rtica como o implante transcateter de valva a&#243;rtica (TAVI), depende de um conjunto de fatores como: gravidade da les&#227;o valvar, dados dos exames complementares, combinados &#224; avalia&#231;&#227;o de multimorbidades, escores de risco, como o STS-score, e avalia&#231;&#227;o funcional (fragilidade e fun&#231;&#227;o cognitiva). Para a decis&#227;o do implante percut&#226;neo, faz-se necess&#225;ria uma equipe multidisciplinar para a&#231;&#245;es integralizadas.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B230"><sup>230</sup></xref> A primeira etapa de uma decis&#227;o cir&#250;rgica &#233; que o paciente possua uma les&#227;o valvar a&#243;rtica grave, que associada &#224; presen&#231;a de sintomas apresente alto grau de recomenda&#231;&#227;o. O tratamento cir&#250;rgico pode ser ainda oferecido aos pacientes assintom&#225;ticos com disfun&#231;&#227;o ventricular (FEVE &lt; 50%) ou j&#225; com programa&#231;&#227;o de outra cirurgia card&#237;aca.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref> Em rela&#231;&#227;o ao risco do procedimento cir&#250;rgico, os pacientes s&#227;o classificados em risco baixo: STS &lt; 4%, sem fragilidade, sem comorbidade; risco intermedi&#225;rio: STS 4% a 8%, fragilidade leve, comprometimento de um sistema org&#226;nico; risco alto: STS &gt; 8%, fragilidade moderada a grave, acometimento mais de dois sistemas org&#226;nicos; risco proibitivo: risco pr&#233;-operat&#243;rio &gt; 50% em 1 ano ou comprometimento de tr&#234;s sistemas org&#226;nicos ou fragilidade extrema.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B231"><sup>231</sup></xref> A decis&#227;o &#233;, na maioria das vezes, complexa, sendo necess&#225;rio envolvimento da fam&#237;lia, da equipe m&#233;dica e multidisciplinar, e principalmente respeitar o desejo do pr&#243;prio paciente. Quando o benef&#237;cio for considerado menor que o risco, o cuidado paliativo pode ser a melhor op&#231;&#227;o para o paciente.</p>
          <table-wrap id="t34">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top" colspan="3">Recomenda&#231;&#245;es para tratamento medicamentoso na EAo</th>
                </tr>
                <tr>
                  <th align="left" valign="middle">Recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">Grau de recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Deve-se tratar a hipertens&#227;o arterial sist&#234;mica em portadores de EAo assintom&#225;ticos, iniciando com dose baixa dos anti-hipertensivos e gradualmente titulando as doses conforme necess&#225;rio e com acompanhamento cl&#237;nico frequente</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Terapia vasodilatadora pode ser utilizada em associa&#231;&#227;o com monitoramento hemodin&#226;mico invasivo no tratamento de pacientes com EAo grave descompensada, com sintomas de IC classe IV da New York Heart Association</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">O uso de estatinas n&#227;o &#233; indicado para preven&#231;&#227;o da progress&#227;o da EAo em pacientes com les&#245;es calcificadas leves a moderadas</td>
                  <td align="center" valign="top">III</td>
                  <td align="center" valign="top">A</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN17a">
                <p><italic>EAo: estenose a&#243;rtica, IC: insufici&#234;ncia card&#237;aca</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <table-wrap id="t35">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top" colspan="3">Recomenda&#231;&#245;es para tratamento cir&#250;rgico na EAo</th>
                </tr>
                <tr>
                  <th align="left" valign="middle">Recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">Grau de recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Pacientes sintom&#225;ticos com EAo grave</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Pacientes assintom&#225;ticos, com EAo grave e FEVE &lt; 50%</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Pacientes com EAo grave que v&#227;o se submeter a outras cirurgias card&#237;acas</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Pacientes assintom&#225;ticos, com EAo muito grave (velocidade de jato transvalvar a&#243;rtico &#8805; 5,0 m/s) e baixo risco cir&#250;rgico</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Pacientes assintom&#225;ticos, com EAo grave e diminui&#231;&#227;o da toler&#226;ncia ao exerc&#237;cio ou hipotens&#227;o no esfor&#231;o</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Pacientes com EAo moderada que v&#227;o se submeter a outras cirurgias card&#237;acas</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Pacientes assintom&#225;ticos, com EAo grave e r&#225;pida progress&#227;o da doen&#231;a, com baixo risco cir&#250;rgico</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN18a">
                <p><italic>EAo: estenose a&#243;rtica; FEVE: fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <table-wrap id="t36">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top" colspan="3">Escolha entre troca valvar a&#243;rtica cir&#250;rgica e TAVI</th>
                </tr>
                <tr>
                  <th align="left" valign="middle">Recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">Grau de recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Troca valvar a&#243;rtica cir&#250;rgica &#233; recomendada em pacientes que tenham indica&#231;&#245;es para o tratamento cir&#250;rgico e que apresentem risco cir&#250;rgico baixo ou intermedi&#225;rio</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Para os pacientes que estejam sendo considerados para realizar TAVI ou os de alto risco cir&#250;rgico para troca valvar, membros de um <italic>Heart Team</italic> devem colaborar para fornecer o melhor atendimento ao paciente</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">TAVI &#233; recomendada em pacientes que tenham indica&#231;&#227;o para troca valvar a&#243;rtica cir&#250;rgica, com risco cir&#250;rgico proibitivo e expectativa de vida p&#243;s- TAVI maior que 12 meses</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">TAVI &#233; uma alternativa razo&#225;vel para a troca valvar a&#243;rtica cir&#250;rgica em pacientes que preencham uma indica&#231;&#227;o para o tratamento cir&#250;rgico e que apresentem alto risco cir&#250;rgico</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Valvuloplastia a&#243;rtica por cateter-bal&#227;o pode ser considerada como uma ponte para troca valvar cir&#250;rgica ou percut&#226;nea em pacientes severamente sintom&#225;ticos com estenose a&#243;rtica grave</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">TAVI n&#227;o &#233; recomendada em pacientes nos quais as comorbidades existentes impediriam os benef&#237;cios esperados da corre&#231;&#227;o da estenose a&#243;rtica</td>
                  <td align="center" valign="top">III</td>
                  <td align="center" valign="top">B</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN19a">
                <p><italic>TAVI: implante transcateter de valva a&#243;rtica</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
      </sec>
      <sec>
        <title>6.4. Insufici&#234;ncia A&#243;rtica</title>
        <sec>
          <title>6.4.1. Peculiaridades no Diagn&#243;stico</title>
          <p>A IAo &#233; menos comum nos idosos do que a EAo e a IM.</p>
          <p>Etiologia &#8211; As causas mais comuns de IAo cr&#244;nica em idosos s&#227;o a dilata&#231;&#227;o da aorta ascendente resultante da HAS, doen&#231;a a&#243;rtica prim&#225;ria, doen&#231;a valvar calcificada e, raramente, uma VAB. Outra causa &#233; a doen&#231;a card&#237;aca reum&#225;tica (principalmente em pa&#237;ses em desenvolvimento).<xref ref-type="bibr" rid="B232"><sup>232</sup></xref></p>
          <p>Sintomas &#8211; A IAo cr&#244;nica evolui na grande maioria dos casos de forma lenta e insidiosa, com morbidade muito baixa durante a fase assintom&#225;tica. Ap&#243;s esta fase, alguns pacientes apresentam progress&#227;o da les&#227;o regurgitante, com subsequente dilata&#231;&#227;o ventricular esquerda, disfun&#231;&#227;o sist&#243;lica e, eventualmente, IC.<xref ref-type="bibr" rid="B233"><sup>233</sup></xref> A taxa de mortalidade para os pacientes com IAo grave com sintomas da classe II da NYHA &#233; de aproximadamente 6% ao ano e de quase 25% em pacientes nas classes III ou IV da NYHA.<xref ref-type="bibr" rid="B234"><sup>234</sup></xref></p>
          <p>Exame f&#237;sico &#8211; O sopro &#233; diast&#243;lico, decrescente, aspirativo e de alta frequ&#234;ncia, melhor aud&#237;vel no rebordo esternal esquerdo ou no foco a&#243;rtico. Sua gravidade se relaciona mais &#224; dura&#231;&#227;o do sopro e menos &#224; sua intensidade. O &#237;ctus est&#225; deslocado, revelando sobrecarga volum&#233;trica de VE, estando sua dimens&#227;o relacionada &#224; gravidade da les&#227;o. As altera&#231;&#245;es perif&#233;ricas, caracter&#237;sticas de gravidade em pacientes jovens (PP aumentada, pulsa&#231;&#227;o arterial de art&#233;rias em pesco&#231;o e pulsa&#231;&#227;o sist&#243;lica da cabe&#231;a), podem estar exacerbadas no idoso, j&#225; que as pr&#243;prias altera&#231;&#245;es resultantes da perda de elasticidade das grandes art&#233;rias no idoso podem acentu&#225;-las.</p>
          <p>Exames complementares &#8211; O ECG &#233; pouco espec&#237;fico na IAo, e o achado habitual &#233; de SVE nos casos de longa dura&#231;&#227;o. A radiografia de t&#243;rax auxilia na detec&#231;&#227;o de comorbidades, avalia&#231;&#227;o de congest&#227;o pulmonar e distin&#231;&#227;o entre casos agudos e cr&#244;nicos. Nos casos agudos mostra congest&#227;o pulmonar e &#225;rea card&#237;aca normal ou pouco aumentada. Nos casos cr&#244;nicos, encontra-se aumento da &#225;rea card&#237;aca secund&#225;rio &#224; dilata&#231;&#227;o do VE. J&#225; a aorta ascendente dilatada sugere que a IAo seja secund&#225;ria &#224; dilata&#231;&#227;o aneurism&#225;tica da aorta. A ecocardiografia &#233; o pilar para monitoramento seriado e avalia&#231;&#227;o de pacientes com IAo cr&#244;nica. Mostra-se &#250;til em confirmar diagn&#243;stico, avaliar causa e morfologia da valva, estimar gravidade da les&#227;o, avaliar dimens&#245;es, massa e fun&#231;&#227;o sist&#243;lica do VE e dimens&#245;es da raiz da aorta.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref> Para pacientes com suspeita de IAo moderada ou grave com achados ecocardiogr&#225;ficos inconclusivos, a resson&#226;ncia magn&#233;tica cardiovascular (RMC) fornece quantifica&#231;&#227;o precisa do volume e fra&#231;&#227;o regurgitante, al&#233;m da medi&#231;&#227;o precisa dos volumes e fun&#231;&#227;o do VE. RMC &#233; particularmente &#250;til quando o grau de dilata&#231;&#227;o do VE parece ser maior do que o esperado para a gravidade na ecocardiografia. O cateterismo card&#237;aco deve ser feito de rotina em todos os pacientes encaminhados para corre&#231;&#227;o cir&#250;rgica, para avalia&#231;&#227;o de doen&#231;a coron&#225;ria, ou quando os exames cl&#237;nicos e laboratoriais s&#227;o duvidosos ou discordantes quanto &#224; gravidade da IAo.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref></p>
        </sec>
        <sec>
          <title>6.4.2. Peculiaridades no Tratamento</title>
          <p>Na IAo grave aguda o tratamento cir&#250;rgico deve ser institu&#237;do o mais precocemente poss&#237;vel, especialmente se existirem sinais e sintomas de baixo d&#233;bito card&#237;aco. Nesses casos o tratamento cl&#237;nico se mostra inferior ao tratamento cir&#250;rgico. F&#225;rmacos inotr&#243;picos e vasodilatadores podem auxiliar no controle cl&#237;nico do paciente enquanto aguarda a cirurgia.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B235"><sup>235</sup></xref></p>
          <p>Tratamento cl&#237;nico &#8211; O tratamento cl&#237;nico de pacientes portadores de IAo com vasodilatadores se aplica &#224;queles com HAS associada e a pacientes com IAo grave sintom&#225;ticos de alto risco para a cirurgia, principalmente devido a comorbidades, para al&#237;vio de sintomas. N&#227;o s&#227;o recomendados rotineiramente para pacientes com IAo cr&#244;nica leve, moderada ou grave assintom&#225;ticos e com fun&#231;&#227;o sist&#243;lica normal.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B235"><sup>235</sup></xref> Estudos n&#227;o demonstraram efic&#225;cia desses f&#225;rmacos no retardo de indica&#231;&#227;o de cirurgia na IAo e n&#227;o substituem a cirurgia quando indicada.<xref ref-type="bibr" rid="B236"><sup>236</sup></xref></p>
          <p>Tratamento cir&#250;rgico &#8211; Pacientes com IAo grave sintom&#225;tica e alguns assintom&#225;ticos t&#234;m reduzida qualidade e expectativa de vida sem o tratamento cir&#250;rgico. A sele&#231;&#227;o do tempo adequado e do tipo de procedimento &#233; primordial para um resultado cir&#250;rgico satisfat&#243;rio, obviamente respeitando a funcionalidade e as comorbidades associadas neste grupo de pacientes.<xref ref-type="bibr" rid="B235"><sup>235</sup></xref> O tratamento cir&#250;rgico &#233; indicado em pacientes com IAo grave sintom&#225;ticos ou naqueles assintom&#225;ticos com FEVE reduzida ou dilata&#231;&#227;o importante do VE.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B235"><sup>235</sup></xref> Recentemente tem-se especulado sobre o reparo valvar a&#243;rtico nesta patologia, pois complica&#231;&#245;es decorrentes do uso de anticoagulante em pacientes que recebem pr&#243;teses mec&#226;nicas n&#227;o s&#227;o raras. Estudos cient&#237;ficos t&#234;m demonstrado que o reparo valvar &#233; preditor independente de melhor sobrevida, com grande redu&#231;&#227;o de necessidade de reopera&#231;&#227;o.<xref ref-type="bibr" rid="B237"><sup>237</sup></xref> No entanto, poucos centros t&#234;m experi&#234;ncia para sua realiza&#231;&#227;o e, no paciente idoso, s&#227;o comuns os achados de folhetos espessados, deformados ou calcificados, que dificultam sua realiza&#231;&#227;o.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref></p>
          <p>Tratamento percut&#226;neo &#8211; O implante percut&#226;neo de valva a&#243;rtica &#233; uma op&#231;&#227;o efetiva em pacientes com IAo e risco cir&#250;rgico moderado ou alto para cirurgia de troca valvar convencional. Na IAo o uso da TAVI ainda &#233; off-label, mas estudos demonstram ser fact&#237;vel e, em pacientes de alto risco, poder&#225; ser uma alternativa de tratamento.<xref ref-type="bibr" rid="B238"><sup>238</sup></xref></p>
          <table-wrap id="t37">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top" colspan="3">Recomenda&#231;&#245;es para tratamento cir&#250;rgico na IAo</th>
                </tr>
                <tr>
                  <th align="left" valign="middle">Recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">Grau de recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Pacientes sintom&#225;ticos com IAo grave, independentemente da fun&#231;&#227;o sist&#243;lica ventricular esquerda</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Pacientes assintom&#225;ticos, com IAo grave e FEVE &lt; 50%</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Pacientes com IAo grave que v&#227;o se submeter a outras cirurgias card&#237;acas</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Pacientes assintom&#225;ticos, com IAo grave, fun&#231;&#227;o sist&#243;lica ventricular esquerda normal (FEVE &#8805; 50%), com dilata&#231;&#227;o importante do VE (DSVE &gt; 50 mm)</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Pacientes com IAo moderada que v&#227;o se submeter a outras cirurgias card&#237;acas</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Pacientes assintom&#225;ticos, com IAo grave e fun&#231;&#227;o sist&#243;lica ventricular esquerda normal (FEVE &gt; 50%), por&#233;m com dilata&#231;&#227;o ventricular esquerda progressiva grave (DDVE &gt; 65 mm), com baixo risco cir&#250;rgico</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN20a">
                <p><italic>DDVE: di&#226;metro diast&#243;lico final do ventr&#237;culo esquerdo; DSVE: di&#226;metro sist&#243;lico do ventr&#237;culo esquerdo; FEVE: fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo; IAo: insufici&#234;ncia a&#243;rtica; VE: ventr&#237;culo esquerdo</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
      </sec>
      <sec>
        <title>6.5. Endocardite Infecciosa</title>
        <sec>
          <title>6.5.1. Peculiaridades no Diagn&#243;stico</title>
          <p>A EI, doen&#231;a anteriormente prevalente em jovens e pacientes de meia-idade, pela associa&#231;&#227;o &#224; doen&#231;a valvar reum&#225;tica, tem aumentado progressivamente na popula&#231;&#227;o idosa,<xref ref-type="bibr" rid="B239"><sup>239</sup></xref> sendo que em pa&#237;ses da Europa e nos Estados Unidos mais da metade dos casos ocorrem em pacientes &gt; 60 anos de idade. O diagn&#243;stico de EI nos idosos pode ser mais dif&#237;cil devido ao fato de sinais e sintomas como confus&#227;o mental, fadiga, perda de peso e presen&#231;a de sopro serem atribu&#237;dos &#224; pr&#243;pria idade. As formas de apresenta&#231;&#227;o da EI nos idosos, como quadro de AVE, IC, pneumonia e dor abdominal, tamb&#233;m podem confundir o diagn&#243;stico inicial. Em algumas casu&#237;sticas a febre aparece em somente 2% dos casos de idosos, diferente do que ocorre com pacientes &lt;60 anos de idade, nos quais &#233; encontrada em 90% dos casos. Outros sintomas pouco espec&#237;ficos, como anorexia, perda de peso, artralgias, dispneia e cefaleia, t&#234;m aparecimento semelhante nos idosos. Sinais perif&#233;ricos cl&#225;ssicos da EI como n&#243;dulos de Osler, manchas de Roth e pet&#233;quias s&#227;o menos frequentes em idosos, sendo encontrados em 1% a 14% dos casos.<xref ref-type="bibr" rid="B240"><sup>240</sup></xref></p>
          <p>Dados laboratoriais e ecocardiogr&#225;ficos &#8211; O hemograma pode ser normal ou apresentar leucocitose, com frequente presen&#231;a de anemia normocr&#244;mica e normoc&#237;tica. A velocidade de hemossedimenta&#231;&#227;o (VHS) pode estar elevada em 90% dos casos. Fator reumatoide positivo &#233; encontrado em 50% dos casos, e a maioria dos pacientes apresenta protein&#250;ria e hemat&#250;ria microsc&#243;pica.<xref ref-type="bibr" rid="B241"><sup>241</sup></xref> Hemoculturas: deve-se proceder &#224; coleta de pelo menos tr&#234;s amostras de sangue nas primeiras 24 horas, com intervalos n&#227;o menores que 15 minutos entre elas, devendo ser coletadas antes do in&#237;cio da antibioticoterapia, pois o seu uso representa a maior causa de n&#227;o identifica&#231;&#227;o do germe respons&#225;vel pela endocardite. Nos pa&#237;ses mais desenvolvidos as hemoculturas atingem 90% a 95% de positividade. Ecocardiograma: com o advento da ecocardiografia na d&#233;cada de 1980,<xref ref-type="bibr" rid="B242"><sup>242</sup></xref> a probabilidade de diagn&#243;stico da EI aumentou, pois a mesma &#233; utilizada para confirmar a presen&#231;a de vegeta&#231;&#245;es, sendo considerada um dos tr&#234;s pilares no diagn&#243;stico da EI, junto &#224; identifica&#231;&#227;o do germe pela hemocultura e aos sinais de comprometimento valvar como os sopros. Nos idosos a sensibilidade e a especificidade do ecocardiograma transtor&#225;cico &#233; menor pela maior frequ&#234;ncia de les&#245;es calcificadas e pr&#243;teses valvares, bem como pela presen&#231;a de obesidade e deformidades tor&#225;cicas.<xref ref-type="bibr" rid="B243"><sup>243</sup></xref> O ETE melhorou a precis&#227;o do diagn&#243;stico, podendo ser realizado nos idosos com a mesma seguran&#231;a que em pacientes mais jovens.</p>
          <p>Crit&#233;rios diagn&#243;sticos &#8211; Em v&#225;rios casos de EI, o diagn&#243;stico &#233; incerto devido &#224; impossibilidade de demonstrar a exist&#234;ncia de vegeta&#231;&#245;es e pelas manifesta&#231;&#245;es cl&#237;nicas inespec&#237;ficas, resultando em erro diagn&#243;stico. Os crit&#233;rios da Duke University, modificados por Li et al.<xref ref-type="bibr" rid="B244"><sup>244</sup></xref> (<xref ref-type="table" rid="t38">Tabela 10</xref>), s&#227;o os mais utilizados para estabelecer o diagn&#243;stico da EI. Apesar de tudo, o diagn&#243;stico da EI em idosos &#233; um processo dif&#237;cil, mas ao inclu&#237;rem-se dados cl&#237;nicos, laboratoriais e ecocardiogr&#225;ficos, reduz-se a possibilidade de erro.</p>
          <table-wrap id="t38">
            <label>Tabela 10</label>
            <caption>
              <title>Crit&#233;rios para diagn&#243;stico de EI</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup width="50%">
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="center" valign="top" colspan="2">Crit&#233;rios maiores</th>
                </tr>
                <tr>
                  <th align="left" valign="top">Microbiol&#243;gico</th>
                  <th align="center" valign="top">Coment&#225;rios</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Microrganismo t&#237;pico isolado de duas hemoculturas separadas: <italic>Streptococcus viridans</italic>, <italic>Streptococcus bovis</italic>, grupo HACEK, <italic>Staphylococcus aureus</italic>, ou bacteriemia por enterococos comunit&#225;rios, na aus&#234;ncia de foco prim&#225;rio</td>
                  <td align="center" valign="top">Em pacientes com poss&#237;vel EI, pelo menos duas hemoculturas coletadas em veias diferentes devem ser obtidas nas primeiras 2 horas. Em pacientes com choque s&#233;ptico, devem ser coletadas tr&#234;s hemoculturas em um intervalo de 5-10 min e, ap&#243;s, iniciar antibioticoterapia emp&#237;rica</td>
                </tr>
                <tr>
                  <td align="left" valign="top" colspan="2">Ou</td>
                </tr>
                <tr>
                  <td align="left" valign="top" colspan="2">Microrganismo consistente com EI isolado de hemoculturas persistentemente positivas</td>
                </tr>
                <tr>
                  <td align="left" valign="top" colspan="2">Ou</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Uma hemocultura positiva para Coxiella burnetii ou t&#237;tulo de anticorpos (lgG) &gt; 1:800 para C. burnetii</td>
                  <td align="center" valign="top">C. burnetii n&#227;o &#233; cultivada na maioria dos laborat&#243;rios de an&#225;lise</td>
                </tr>
                <tr>
                  <td align="left" valign="top" colspan="2">Evid&#234;ncias de envolvimento endoc&#225;rdico</td>
                </tr>
                <tr>
                  <td align="left" valign="top" colspan="2">Novas insufici&#234;ncias valvares (aumento e mudan&#231;as em sopros preexistentes n&#227;o s&#227;o suficientes)</td>
                </tr>
                <tr>
                  <td align="left" valign="top" colspan="2">Ou</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Ecocardiograma positivo (ETE recomendado em pacientes com pr&#243;teses, com EI poss&#237;vel, baseado em crit&#233;rios cl&#237;nicos, ou com EI complicada)</td>
                  <td align="center" valign="top">Tr&#234;s achados do ETT considerados crit&#233;rios maiores: discreta massa intracard&#237;aca pedunculada, localizada na valva ou na estrutura subvalvar; abscesso perianular e nova deisc&#234;ncia de pr&#243;tese valvar</td>
                </tr>
                <tr>
                  <td align="left" valign="top">
                    <bold>Crit&#233;rios menores</bold>
                  </td>
                  <td align="center" valign="top">
                    <bold>Coment&#225;rios</bold>
                  </td>
                </tr>
                <tr>
                  <td align="left" valign="top" rowspan="4">Predisposi&#231;&#227;o a EI, incluindo certas condi&#231;&#245;es card&#237;acas e uso de agentes IV</td>
                  <td align="center" valign="top">Anormalidades card&#237;acas que est&#227;o associadas &#224; EI s&#227;o classificadas em tr&#234;s grupos:</td>
                </tr>
                <tr>
                  <td align="center" valign="top">&#9679; Alto risco: EI pr&#233;via, doen&#231;a valvar a&#243;rtica, doen&#231;a valvar reum&#225;tica, pr&#243;tese valvar, coarcta&#231;&#227;o de aorta e cardiopatias cian&#243;ticas complexas</td>
                </tr>
                <tr>
                  <td align="center" valign="top">&#9679; M&#233;dio risco: prolapso de valva mitral com insufici&#234;ncia ou espessamento de folhetos, estenose mitral isolada, valvopatia tric&#250;spide, estenose pulmonar, cardiomiopatia hipertr&#243;fica</td>
                </tr>
                <tr>
                  <td align="center" valign="top">&#9679; Baixo risco: CIA tipo ostium secundum, doen&#231;a isqu&#234;mica, cirurgia de revasculariza&#231;&#227;o pr&#233;via e prolapso de valva mitral sem regurgita&#231;&#227;o pr&#233;via e prolapso de valva mitral sem regurgita&#231;&#227;o e com folhetos finos</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Febre</td>
                  <td align="center" valign="top">Temperatura &gt; 38&#176; C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Fen&#244;menos vasculares</td>
                  <td align="center" valign="top">Exceto pet&#233;quias e sufus&#245;es hemorr&#225;gicas</td>
                </tr>
                <tr>
                  <td align="left" valign="top"/>
                  <td align="center" valign="top">Nenhuma das les&#245;es perif&#233;ricas &#233; patognom&#244;nica de EI</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Fen&#244;menos imunol&#243;gicos</td>
                  <td align="center" valign="top">Presen&#231;a de fator reumatoide, glomerulonefrite, n&#243;dulos de Osler, manchas de Roth</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Achados microbiol&#243;gicos</td>
                  <td align="center" valign="top">Hemoculturas positivas que n&#227;o preencham os crit&#233;rios maiores. Evid&#234;ncias sorol&#243;gicas de infec&#231;&#227;o ativa, isolamento de estafilococos coagulase-negativos e organismos que muito raramente causam EI s&#227;o exclu&#237;dos desta categoria</td>
                </tr>
                <tr>
                  <td align="left" valign="top" colspan="2">Os casos s&#227;o definidos clinicamente como EI definitiva se preenchem dois crit&#233;rios maiores, um maior e tr&#234;s menores ou cinco menores; EI poss&#237;vel, um maior e um menor, ou tr&#234;s menores.</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN9">
                <p><italic>CIA: comunica&#231;&#227;o interatrial; EI: endocardite infecciosa; ETE: ecocardiograma transesof&#225;gico; ETT: ecocardiograma transtor&#225;cico; HACEK: Haemophilus aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenellacorrodens e Kingella kingae; IgG: imunoglobulina G; IV: via intravenosa</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>6.5.2. Peculiaridades no Tratamento</title>
          <p>Com o envelhecimento populacional a EI vem acometendo cada vez mais idosos. Mais de um ter&#231;o dos pacientes com EI nos pa&#237;ses ocidentais tem mais de 70 anos de idade.<xref ref-type="bibr" rid="B245"><sup>245</sup></xref> A mortalidade nos idosos tamb&#233;m &#233; maior quando comparada com a da popula&#231;&#227;o geral.<xref ref-type="bibr" rid="B246"><sup>246</sup></xref> O envelhecimento &#233; um processo heterog&#234;neo e &#233; sempre recomend&#225;vel a AGA, que considera os estados nutricional, funcional e cognitivo, para melhor se definir o progn&#243;stico como tamb&#233;m a op&#231;&#227;o de tratamento nesta popula&#231;&#227;o.<xref ref-type="bibr" rid="B247"><sup>247</sup></xref> A maior parte dos pacientes idosos com EI apresenta multimorbidades e as portas de entrada da bact&#233;ria s&#227;o mais frequentemente o trato digestivo e o trato urin&#225;rio. Al&#233;m disso, estes pacientes apresentam fatores predisponentes como EAo, pr&#243;teses valvares e dispositivos intracard&#237;acos.<xref ref-type="bibr" rid="B248"><sup>248</sup></xref> Na defini&#231;&#227;o do tratamento a literatura internacional n&#227;o faz considera&#231;&#245;es sobre a idade e suas consequ&#234;ncias nas escolhas do tratamento.<xref ref-type="bibr" rid="B248"><sup>248</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B250"><sup>250</sup></xref> Dados da AGA e a presen&#231;a da s&#237;ndrome da fragilidade devem ser fatores a serem considerados na decis&#227;o sobre o tratamento proposto.<xref ref-type="bibr" rid="B207"><sup>207</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B240"><sup>240</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B250"><sup>250</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B251"><sup>251</sup></xref> A <xref ref-type="table" rid="t39">Tabela 11</xref> exemplifica as poss&#237;veis adapta&#231;&#245;es nos idosos. Pacientes idosos apresentam, em sua maioria, decl&#237;nio da fun&#231;&#227;o renal; portanto, os antibi&#243;ticos nefrot&#243;xicos devem ser usados com cuidado e em alguns casos at&#233; mesmo evitados nessa popula&#231;&#227;o.<xref ref-type="bibr" rid="B252"><sup>252</sup></xref> O tratamento da EI costuma acarretar interna&#231;&#227;o prolongada. Na popula&#231;&#227;o idosa a interna&#231;&#227;o prolongada est&#225; associada a piora funcional e cognitiva. O uso de antibioticoterapia parenteral ambulatorial deve ser estimulado nessa popula&#231;&#227;o, evitando as complica&#231;&#245;es da interna&#231;&#227;o prolongada; para isto, o paciente deve ter infec&#231;&#227;o controlada, quadro cl&#237;nico estabilizado e um acesso venoso de longa perman&#234;ncia. No caso de idosos com dificuldades de acesso venoso, a via subcut&#226;nea ou at&#233; mesmo a oral podem ser consideradas, dependendo do antibi&#243;tico em uso.<xref ref-type="bibr" rid="B252"><sup>252</sup></xref> No caso do tratamento cir&#250;rgico, as indica&#231;&#245;es s&#227;o as mesmas da popula&#231;&#227;o geral (les&#227;o valvar grave com IC, vegeta&#231;&#227;o grande com risco de embolia sist&#234;mica e infec&#231;&#227;o n&#227;o controlada), por&#233;m a AGA neste contexto ganha import&#226;ncia na decis&#227;o do tratamento cir&#250;rgico pelos riscos de as multimorbidades existentes poderem interferir com os procedimentos planejados. Nesses casos, uma avalia&#231;&#227;o cuidadosa do risco/benef&#237;cio dos procedimentos deve ser realizada de maneira individualizada.<xref ref-type="bibr" rid="B253"><sup>253</sup></xref> Esta decis&#227;o deve ser realizada de modo multidisciplinar e, quando poss&#237;vel, envolver a opini&#227;o de infectologista, cardiologista, cirurgi&#227;o card&#237;aco, anestesiologista e geriatra, para se tentar definir com maior precis&#227;o os pacientes que se beneficiariam ou n&#227;o de um procedimento cir&#250;rgico, quando indicado.<xref ref-type="bibr" rid="B252"><sup>252</sup></xref></p>
          <table-wrap id="t39">
            <label>Tabela 11</label>
            <caption>
              <title>Adapta&#231;&#245;es das diretrizes de 2015 aos idosos de acordo com comorbidades e estado funcional<xref ref-type="bibr" rid="B252"><sup>252</sup></xref></title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="center" valign="top"/>
                  <th align="center" valign="top">Diretrizes</th>
                  <th align="center" valign="top">Sugest&#245;es em idosos</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Ecocardiograma transesof&#225;gico</td>
                  <td align="center" valign="top">Considerar em todos os casos de acordo com a suspeita</td>
                  <td align="center" valign="top">Avaliar risco/benef&#237;cio do procedimento</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Aminoglicos&#237;deos</td>
                  <td align="center" valign="top">Combinados com penicilina ou vancomicina como primeira escolha</td>
                  <td align="center" valign="top">Evitar pela nefrotoxicidade. Avaliar alternativas</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Vancomicina</td>
                  <td align="center" valign="top">Primeira linha de tratamento em al&#233;rgicos a betalact&#226;micos ou em casos de MRSA</td>
                  <td align="center" valign="top">Considerar daptomicina para evitar nefrotoxicidade</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Monitoramento s&#233;rico de antibi&#243;ticos</td>
                  <td align="center" valign="top">Vancomicina e aminoglicos&#237;deos</td>
                  <td align="center" valign="top">Considerar tamb&#233;m para betalact&#226;micos</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Terapia intravenosa</td>
                  <td align="center" valign="top">Todos os casos</td>
                  <td align="center" valign="top">Considerar a via oral ou subcut&#226;nea</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Terapia parenteral ambulatorial</td>
                  <td align="center" valign="top">Somente em pacientes colaborativos e que tenham facilidade de acesso ao hospital</td>
                  <td align="center" valign="top">Considerar em pacientes em que interna&#231;&#227;o prolongada possa ser delet&#233;ria para os estados funcional e cognitivo</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN10">
                <p>
                  <italic>MRSA: Staphylococcus aureus resistente &#224; meticilina. Adaptada de Forestier et al., 2016.</italic>
                  <xref ref-type="bibr" rid="B252">
                    <sup>252</sup>
                  </xref>
                </p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
      </sec>
    </sec>
    <sec>
      <title>7. Arritmias Card&#237;acas</title>
      <p>As arritmias e os dist&#250;rbios de condu&#231;&#227;o s&#227;o comuns no paciente idoso e configuram importante causa de atendimentos de urg&#234;ncia e hospitaliza&#231;&#227;o neste grupo et&#225;rio.<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> Altera&#231;&#245;es estruturais no sistema cardiovascular, promovidas pelo envelhecimento, associadas &#224; maior incid&#234;ncia de comorbidades como HVE, DAC, valvopatia degenerativa, HAS, disfun&#231;&#227;o ventricular esquerda, doen&#231;as pulmonares, al&#233;m da polifarm&#225;cia, s&#227;o respons&#225;veis pela preval&#234;ncia aumentada de arritmias nesta popula&#231;&#227;o.<xref ref-type="bibr" rid="B254"><sup>254</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B258"><sup>258</sup></xref> A avalia&#231;&#227;o cl&#237;nica deve ser minuciosa, uma vez que muitos idosos apresentam manifesta&#231;&#245;es at&#237;picas como quedas inexplicadas, confus&#227;o mental intermitente, eventos tromboemb&#243;licos, s&#237;ncope ou mesmo cursam assintom&#225;ticos e s&#227;o detectados casualmente em um ECG de rotina.<xref ref-type="bibr" rid="B257"><sup>257</sup></xref> A presen&#231;a de multimorbidades, s&#237;ndrome da fragilidade, comprometimento da funcionalidade e da fun&#231;&#227;o cognitiva interfere no manejo das arritmias neste grupo, que deve ser individualizado.</p>
      <p>Nesta se&#231;&#227;o, ser&#227;o discutidas as peculiaridades diagn&#243;sticas e do tratamento das principais arritmias card&#237;acas nos idosos.</p>
      <sec>
        <title>7.1. S&#237;ncope e Bradiarritmias</title>
        <sec>
          <title>7.1.1. S&#237;ncope e seus Diagn&#243;sticos Diferenciais no Idoso</title>
          <p>A s&#237;ncope no idoso tem etiologia multifatorial, sendo comum a hipotens&#227;o postural (ortost&#225;tica; HO), secund&#225;ria a medica&#231;&#245;es em uso e arritmias graves. Tem preval&#234;ncia m&#233;dia de 6%, aumentando de forma exponencial com a idade.<xref ref-type="bibr" rid="B254"><sup>254</sup></xref> Tem taxa de recorr&#234;ncia de 25% a 30% ao ano, nos 2 primeiros anos.<xref ref-type="bibr" rid="B255"><sup>255</sup></xref> &#201; preditor independente de morbimortalidade, redu&#231;&#227;o da capacidade funcional e institucionaliza&#231;&#227;o,<xref ref-type="bibr" rid="B257"><sup>257</sup></xref> al&#233;m de motivo frequente de admiss&#245;es hospitalares. As s&#237;ncopes cardiog&#234;nicas s&#227;o as de pior progn&#243;stico, respondendo por at&#233; 20% dos casos no idoso.<xref ref-type="bibr" rid="B258"><sup>258</sup></xref> As bradiarritmias (doen&#231;a do n&#243; sinusal ou bloqueios atrioventriculares &#8211; BAV avan&#231;ados) s&#227;o comumente relacionadas a s&#237;ncope no idoso. As taquiarritmias manifestam-se com s&#237;ncope em menor frequ&#234;ncia; s&#227;o manifesta&#231;&#245;es do tipo &#8220;liga-desliga&#8221;, de in&#237;cio s&#250;bito, sem pr&#243;dromos de curta dura&#231;&#227;o, sem rela&#231;&#227;o com posi&#231;&#227;o ortost&#225;tica e de recupera&#231;&#227;o r&#225;pida. Lembrar da EAo como poss&#237;vel causa da s&#237;ncope induzida por esfor&#231;o induzida em idosos. S&#227;o considerados como preditores da s&#237;ncope cardiog&#234;nica, segundo o escore EGSYS 2 (Evaluation of Guidelines in SYncope Study 2): presen&#231;a de anormalidades ao ECG, cardiopatia estrutural, palpita&#231;&#245;es antecedendo a s&#237;ncope, s&#237;ncope ao esfor&#231;o ou na posi&#231;&#227;o deitada, aus&#234;ncia de pr&#243;dromos auton&#244;micos, aus&#234;ncia de fatores desencadeantes ou precipitantes (&#8805; 3 pontos sugerem s&#237;ncope cardiog&#234;nica).<xref ref-type="bibr" rid="B259"><sup>259</sup></xref> A presen&#231;a de dispneia antecedendo a s&#237;ncope tamb&#233;m sugere etiologia cardiog&#234;nica.<xref ref-type="bibr" rid="B258"><sup>258</sup></xref> A s&#237;ncope por hipotens&#227;o postural &#233; comum em pacientes desidratados e com diminui&#231;&#227;o do volume intravascular. Sua preval&#234;ncia aumenta com a idade, variando de 6% em estudos populacionais a 70% em pacientes internados, institucionalizados e portadores de doen&#231;a de Parkinson.<xref ref-type="bibr" rid="B260"><sup>260</sup></xref> Nas s&#237;ndromes demenciais, 48% dos epis&#243;dios de s&#237;ncope ocorrem por HO.<xref ref-type="bibr" rid="B261"><sup>261</sup></xref> S&#237;ncopes at&#233; 2 horas ap&#243;s uma refei&#231;&#227;o principal devem remeter ao diagn&#243;stico de hipotens&#227;o p&#243;s-prandial. As s&#237;ncopes neuromediadas s&#227;o frequentes nos idosos. Dentre estas, as mais prevalentes s&#227;o as situacionais (associadas a mic&#231;&#227;o, defeca&#231;&#227;o, tosse e hipersensibilidade do seio carot&#237;deo).<xref ref-type="bibr" rid="B258"><sup>258</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B259"><sup>259</sup></xref> A presen&#231;a de n&#225;useas, vis&#227;o borrada e sudorese sugere causa n&#227;o cardiog&#234;nica (HO ou neurocardiog&#234;nica).<xref ref-type="bibr" rid="B258"><sup>258</sup></xref> A s&#237;ncope de causa neurol&#243;gica, por insufici&#234;ncia vertebrobasilar bilateral preexistente, habitualmente acompanha-se de sintomas como vertigem e ataxia, tendo menor preval&#234;ncia. H&#225; ainda que se considerar a s&#237;ncope como manifesta&#231;&#227;o at&#237;pica de doen&#231;as graves como IAM, que ocorre em at&#233; 3% nos idosos &gt; 65 anos,<xref ref-type="bibr" rid="B262"><sup>262</sup></xref> sendo comum em idosos &gt; 85 anos de idade, nos quais a preval&#234;ncia chega a 20%,<xref ref-type="bibr" rid="B263"><sup>263</sup></xref> tromboembolismo pulmonar (TEP) (24% dos idosos &gt; 65 anos)<xref ref-type="bibr" rid="B264"><sup>264</sup></xref> e dissec&#231;&#227;o a&#243;rtica aguda (5% a 10%).<xref ref-type="bibr" rid="B265"><sup>265</sup></xref></p>
          <sec>
            <title>7.1.1.1. Estratifica&#231;&#227;o do Risco de Morte</title>
            <p>O <italic>San Francisco Syncope Rules</italic> (SFS) &#233; uma regra simples que avalia o risco de eventos adversos em pacientes com s&#237;ncope. Tem sensibilidade de 74% a 98% e especificidade de 56%.<xref ref-type="bibr" rid="B266"><sup>266</sup></xref> A baixa especificidade se deve ao fato de ser pouco espec&#237;fico para s&#237;ncope cardiog&#234;nica, mas permite liberar pacientes de baixo risco e internar os de maior gravidade. O mnem&#244;nico do escore S&#227;o Francisco para S&#237;ncope &#233; o seguinte:</p>
            <disp-quote>
              <p>C &#8211; Hist&#243;ria de ICC.</p>
              <p>H &#8211; Hemat&#243;crito &lt; 30%.</p>
              <p>E &#8211; ECG anormal.</p>
              <p>S &#8211; Falta de ar.</p>
              <p>S &#8211; PAS na admiss&#227;o &lt; 90 mmHg.</p>
              <p>(A) &#8211; Idade &gt; 75 anos.</p>
            </disp-quote>
            <p>Em um paciente com s&#237;ncope, qualquer um dos achados anteriores &#233; considerado de alto risco para eventos graves como morte, IAM, arritmia, TEP, AVE,hemorragia subaracn&#243;idea, ou readmiss&#227;o na emerg&#234;ncia e interna&#231;&#227;o relacionada a um novo epis&#243;dio de s&#237;ncope. Ao acrescentarmos a idade, a sensibilidade aumenta para 100%, embora reduza a especificidade.</p>
            <p>Um outro escore &#250;til que se soma ao anterior &#233; o do <italic>Short-Term Prognosis of Syncope (STePS) Study</italic>,<xref ref-type="bibr" rid="B267"><sup>267</sup></xref> que avaliou o risco de eventos em 10 dias ap&#243;s a s&#237;ncope. Inclui apenas quatro preditores independentes de risco:</p>
            <list list-type="bullet">
              <list-item>
                <p>ECG anormal (melhor preditor).</p>
              </list-item>
              <list-item>
                <p>Traumatismo concomitante.</p>
              </list-item>
              <list-item>
                <p>Aus&#234;ncia de pr&#243;dromos.</p>
              </list-item>
              <list-item>
                <p>Sexo masculino.</p>
              </list-item>
            </list>
            <p>Preditores de mau progn&#243;stico em longo prazo (1 ano) incluem: ECG anormal, arritmia ventricular, IC e idade &gt; 45 anos. A taxa de eventos (arritmia grave ou morte) em 1 ano varia de 0% para pacientes sem nenhum dos 4 fatores de risco a 27% nos pacientes com &#8805; 3 fatores. Assim, podemos considerar como de alto risco de eventos em curto (7 e 10 dias) e longo prazos (1 ano) os idosos que apresentam s&#237;ncope e:</p>
            <list list-type="bullet">
              <list-item>
                <p>G&#234;nero masculino.</p>
              </list-item>
              <list-item>
                <p>Sem pr&#243;dromos e com traumatismo concomitante &#224; s&#237;ncope.</p>
              </list-item>
              <list-item>
                <p>T&#234;m dispneia ou hipotens&#227;o mantida associadas ao evento sincopal.</p>
              </list-item>
              <list-item>
                <p>Com diagn&#243;stico pr&#233;vio de IC e/ou arritmias ventriculares.</p>
              </list-item>
              <list-item>
                <p>ECG alterado &#224; admiss&#227;o.</p>
              </list-item>
            </list>
          </sec>
          <sec>
            <title>7.1.1.2. Recomenda&#231;&#245;es Gerais</title>
            <p>Idosos com relato de quedas recorrentes inexplicadas, n&#227;o presenciadas por terceiros e associadas a traumatismo devem ser interpretados como apresentando poss&#237;veis s&#237;ncopes cardiog&#234;nicas. A investiga&#231;&#227;o deve ser em ambiente hospitalar para epis&#243;dios ocorridos h&#225; &lt; 1 semana, com traumatismo ou nos pacientes com cardiopatia conhecida. Pacientes com epis&#243;dio &#250;nico, ocorrido h&#225; &gt; 1 semana, sem traumatismo, podem ser investigados ambulatorialmente. Todos os pacientes idosos &gt; 75 anos de idade, com diagn&#243;stico pr&#233;vio de cardiopatia e ECG anormal, devem ser investigados em &#226;mbito hospitalar, pela alta probabilidade de s&#237;ncope cardiog&#234;nica. O fluxograma da <xref ref-type="fig" rid="f2">Figura 2</xref> sugere uma rota de investiga&#231;&#227;o, com base em estratifica&#231;&#227;o de risco, hist&#243;ria cl&#237;nica e exame f&#237;sico, os quais ir&#227;o definir a estrat&#233;gia de investiga&#231;&#227;o e tratamento.</p>
            <fig id="f2">
              <label>Figura 2</label>
              <caption>
                <title><italic>Fluxograma para investiga&#231;&#227;o de s&#237;ncope em idosos. SFS: San Francisco Syncope Rules</italic>.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-112-05-0649-90086-gf02.tif"/></fig>
          </sec>
        </sec>
        <sec>
          <title>7.1.2. Peculiaridades no Diagn&#243;stico das Bradiarritmias</title>
          <p>Os bloqueios atrioventriculares (BAV) de primeiro grau t&#234;m preval&#234;ncia de 6% a 8% em indiv&#237;duos &#8805; 70 anos de idade e, assim como os BAV de segundo grau tipo Mobitz I, n&#227;o s&#227;o preditivos para eventos cardiovasculares. J&#225; o BAV de segundo grau tipo Mobitz II ou BAV de terceiro grau apresentam pior progn&#243;stico e necessitam tratamento. A presen&#231;a de bradicardia extrema (&lt; 35 bpm), pausas sinusais &gt; 2 segundos ou BAV avan&#231;ado est&#225; associada a cardiopatia estrutural e, habitualmente, &#233; sintom&#225;tica. &#201; comum a associa&#231;&#227;o de bradicardia induzida por f&#225;rmacos cronotr&#243;picos negativos, inibidores da acetilcolinesterase ou anticolinester&#225;sicos (rivastigmina, donepezila e galantamina) e alfabloqueadores centrais usados para sintomas prost&#225;ticos ou HAS. Muitos casos s&#227;o assintom&#225;ticos, diagnosticados casualmente em consulta de rotina, principalmente nos pacientes sedent&#225;rios ou com limita&#231;&#227;o funcional.<xref ref-type="bibr" rid="B268"><sup>268</sup></xref> Dentre os sintomas comuns est&#227;o a tontura n&#227;o girat&#243;ria e a dispneia ou fadiga induzidas por esfor&#231;o, ocasionadas pelo d&#233;ficit cronotr&#243;pico. Um sintoma de alerta &#233; a cl&#225;ssica s&#237;ncope do tipo &#8220;liga-desliga&#8221; (s&#237;ndrome de Stokes-Adams), ocasionada pelo BAV total ou de alto grau intermitente.<xref ref-type="bibr" rid="B269"><sup>269</sup></xref> O diagn&#243;stico pode ser realizado pelo ECG de 12 deriva&#231;&#245;es, Holter 24h, monitor de eventos (Looper) e estudo eletrofisiol&#243;gico (EEF). O Holter &#233; indicado nos pacientes bradic&#225;rdicos que apresentam sintomas di&#225;rios. O monitor de eventos (implant&#225;vel ou port&#225;til) &#233; indicado para surpreender sintomas de ocorr&#234;ncia pouco frequente, por&#233;m com comprometimento hemodin&#226;mico importante e dura&#231;&#227;o prolongada que coloquem em risco a vida do paciente idoso.<xref ref-type="bibr" rid="B270"><sup>270</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B274"><sup>274</sup></xref> Nos casos de sintomas induzidos por esfor&#231;os, o TE em esteira pode esclarecer a suspeita diagn&#243;stica (incompet&#234;ncia cronotr&#243;pica ou graus avan&#231;ados de BAV). Nos pacientes com com Holter 24h ou Looper inconclusivos e s&#237;ncope recorrente inexplicada, est&#225; indicada a realiza&#231;&#227;o de EEF.</p>
          <table-wrap id="t40">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top" colspan="3">Recomenda&#231;&#245;es gerais quanto ao diagn&#243;stico das bradiarritmias no idoso</th>
                </tr>
                <tr>
                  <th align="left" valign="middle">Recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">Grau de recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">ECG de 12 deriva&#231;&#245;es para pacientes com suspeita de bradiarritmia</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Investigar o uso de f&#225;rmacos cronotr&#243;picos negativos e sintomas ao esfor&#231;o em assintom&#225;ticos com bradicardia</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Holter 24h para correla&#231;&#227;o eletrocardiogr&#225;fica de sintomas com a bradicardia (pr&#233;-s&#237;ncope, s&#237;ncope, palpita&#231;&#245;es, dispneia de esfor&#231;o, fadiga desproporcional ao esfor&#231;o ou tontura n&#227;o girat&#243;ria)</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Holter 24h para pacientes com bradicardia sinusal de repouso, assintom&#225;ticos</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Holter 24h para pacientes com bradicardia sinusal de repouso com sintomas ao esfor&#231;o para avaliar graus avan&#231;ados de bloqueio ou pausas</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Holter 24h em paciente com BAV de alto grau ou BAV total intermitente, assintom&#225;tico sem f&#225;rmaco cronotr&#243;pico negativo</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Holter 24h em pacientes com s&#237;ncope, pr&#233;-s&#237;ncope, tontura, em que a causa prov&#225;vel, &#224; exce&#231;&#227;o de bradiarritmias, tenha sido identificada, mas com persist&#234;ncia dos sintomas mesmo com tratamento da prov&#225;vel causa e em recuperados de PCR</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Holter 24h para correla&#231;&#227;o eletrocardiogr&#225;fica de sintomas inespec&#237;ficos como tontura girat&#243;ria, dispneia, sudorese em pacientes sem bradicardia documentada</td>
                  <td align="center" valign="top">III</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Holter 24h para todos os pacientes com tontura</td>
                  <td align="center" valign="top">III</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Looper ou Holter de 7 dias em pacientes com pr&#233;-s&#237;ncope, s&#237;ncope, palpita&#231;&#245;es, dispneia de esfor&#231;o, fadiga desproporcional ao esfor&#231;o ou tontura n&#227;o girat&#243;ria pouco frequentes</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Looper ou Holter de 7 dias em pacientes com s&#237;ncope, pr&#233;-sincope, tontura, em que a causa prov&#225;vel, &#224; exce&#231;&#227;o de bradiarritmias, tenha sido identificada, mas com persist&#234;ncia dos sintomas mesmo com tratamento da prov&#225;vel causa, pouco frequentes</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Looper ou Holter de 7 dias para correla&#231;&#227;o eletrocardiogr&#225;fica de sintomas inespec&#237;ficos como tontura girat&#243;ria, dispneia, sudorese em pacientes sem bradicardia documentada</td>
                  <td align="center" valign="top">III</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Teste ergom&#233;trico em esteira para pacientes com sintomas induzidos por esfor&#231;o e bradicardia sinusal de repouso para avalia&#231;&#227;o de incompet&#234;ncia cronotr&#243;pica</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Teste ergom&#233;trico em esteira para pacientes sem sintomas e bradicardia sinusal de repouso</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Estudo eletrofisiol&#243;gico em pacientes com suspeita cl&#237;nica de bradiarritmia e exames n&#227;o invasivos inconclusivos para medir intervalos AH, HV e de tempo de recupera&#231;&#227;o sinusal (investiga&#231;&#227;o de doen&#231;a do n&#243; sinusal e n&#243; atrioventricular degenerativa)</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN21a">
                <p><italic>BAV: bloqueio atrioventricular; ECG: eletrocardiograma; PCR: parada cardiorrespirat&#243;ria</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>7.1.3. Peculiaridades no Tratamento</title>
          <p>Tratamento da s&#237;ncope &#8211; O tratamento da s&#237;ncope no idoso deve ser multifatorial, com uma abordagem que alcance v&#225;rios dos componentes que possam estar envolvidos com o evento sincopal. Os casos de s&#237;ncope cardiog&#234;nica em nada diferem da abordagem nos pacientes mais jovens. Tratamento da doen&#231;a card&#237;aca de base conforme as recomenda&#231;&#245;es espec&#237;ficas, respeitando-se as especificidades do paciente idoso.<xref ref-type="bibr" rid="B254"><sup>254</sup></xref> Evitar hipovolemia e substituir medicamentos vasodilatadores que possam promover HO, por acentuar a resposta disauton&#244;mica como betabloqueadores de a&#231;&#227;o alfa e betabloqueadora, nitratos, bloqueadores dos canais de c&#225;lcio e alfabloqueadores centrais. F&#225;rmacos de a&#231;&#227;o central tamb&#233;m est&#227;o associados a risco de s&#237;ncope e devem ser substitu&#237;dos (tric&#237;clicos, fluoxetina, aceprometazina, haloperidol, L-dopa, entre outros).<xref ref-type="bibr" rid="B275"><sup>275</sup></xref> As medidas n&#227;o farmacol&#243;gicas comumente prescritas para tratamento das s&#237;ncopes neuromediadas t&#234;m resultados conflitantes na popula&#231;&#227;o idosa, al&#233;m da dificuldade de ades&#227;o. Liberar a ingesta de s&#243;dio e estimular a ingesta h&#237;drica s&#227;o eficazes, por&#233;m com baixa ades&#227;o.<xref ref-type="bibr" rid="B276"><sup>276</sup></xref> Evitar alimenta&#231;&#227;o copiosa e em temperaturas elevadas, bem como levantar-se subitamente ap&#243;s as principais refei&#231;&#245;es pode reduzir a ocorr&#234;ncia de hipotens&#227;o p&#243;s-prandial. O tratamento medicamentoso cl&#225;ssico da s&#237;ncope neuromediada tamb&#233;m n&#227;o se mostrou eficaz no idoso.<xref ref-type="bibr" rid="B277"><sup>277</sup></xref> Dos f&#225;rmacos, a fludrocortisona tem efic&#225;cia comprovada nessa faixa et&#225;ria, &#224; custa de mais efeitos colaterais, principalmente edema, hipocalemia, alcalose metab&#243;lica, ganho de peso e hipertens&#227;o supina.<xref ref-type="bibr" rid="B277"><sup>277</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B278"><sup>278</sup></xref> O tratamento das s&#237;ncopes cardioinibit&#243;rias com marca-passo (MP) no idoso mostrou reduzir recorr&#234;ncia da s&#237;ncope no &#250;nico ensaio cl&#237;nico randomizado realizado nesta popula&#231;&#227;o (5% versus 61% de recorr&#234;ncia nos grupos marca-passo e controle, respectivamente, p = 0,00000).<xref ref-type="bibr" rid="B279"><sup>279</sup></xref></p>
          <p>Tratamento das bradiarritmias &#8211; O tratamento das bradiarritmias no idoso segue as mesmas recomenda&#231;&#245;es dos mais jovens.<xref ref-type="bibr" rid="B280"><sup>280</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B281"><sup>281</sup></xref> A suspens&#227;o de f&#225;rmacos cronotr&#243;picos negativos &#233; fundamental. Nos pacientes com bradicardia sinusal sintom&#225;ticos, FC &lt; 40 bpm em repouso ou com pausas sintom&#225;ticas, a indica&#231;&#227;o de implante de MP definitivo reduz sintomas e melhora qualidade de vida, mas n&#227;o interfere no progn&#243;stico.<xref ref-type="bibr" rid="B282"><sup>282</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B283"><sup>283</sup></xref> Pacientes portadores de bradicardia sinusal e com quadro demencial que precisam iniciar inibidores da colinesterase, podem ter seu quadro de bradiarritmia agravado, sendo o efeito dose-dependente. A indica&#231;&#227;o de MP nesses pacientes deve ser individualizada, uma vez que n&#227;o existe evid&#234;ncia de efic&#225;cia quanto a esta abordagem. Nos pacientes com BAV avan&#231;ado, a indica&#231;&#227;o de MP definitivo est&#225; associada a redu&#231;&#227;o da mortalidade e deve seguir as mesmas indica&#231;&#245;es dos pacientes jovens.<xref ref-type="bibr" rid="B280"><sup>280</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B281"><sup>281</sup></xref></p>
          <p>Recomenda&#231;&#245;es gerais &#8211; No que se refere ao tratamento de s&#237;ncope e bradiarritmias no idoso, &#233; importante a avalia&#231;&#227;o multiprofissional quanto ao aspecto funcional e progn&#243;stico das comorbidades. De uma forma geral, n&#227;o h&#225; especificidade quanto &#224; efic&#225;cia do tratamento das interven&#231;&#245;es no que diz respeito &#224;s bradiarritmias, devendo as recomenda&#231;&#245;es de tratamento ser seguidas como nos mais jovens. Atentar para os f&#225;rmacos com propriedades cronotr&#243;picas negativas de uso n&#227;o cardiovascular que podem agravar bradicardia preexistente.</p>
        </sec>
      </sec>
      <sec>
        <title>7.2. Taquiarritimias no Idoso</title>
        <sec>
          <title>7.2.1. Peculiaridades no Diagn&#243;stico</title>
          <p>Taquiarritmias supraventriculares (TSV) &#8211; As TSV s&#227;o frequentes no idoso e sua preval&#234;ncia aumenta com a idade. As mais comuns nesta faixa et&#225;ria s&#227;o: a taquicardia atrial, o flutter e a FA.<xref ref-type="bibr" rid="B284"><sup>284</sup></xref> As extrass&#237;stoles atriais (EA) em pacientes de 60 a 86 anos de idade t&#234;m preval&#234;ncia aproximada de 80% e a taquicardia parox&#237;stica supraventricular (TPSV), de 10 a 15%. Nos indiv&#237;duos &#8805; 80 anos de idade a preval&#234;ncia de EA chega a 100% e a de TPSV, a 25% a 30%. As arritmias atriais induzidas por esfor&#231;o nos pacientes &gt; 80 anos de idade alcan&#231;am preval&#234;ncia &gt; 10%.<xref ref-type="bibr" rid="B285"><sup>285</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B286"><sup>286</sup></xref> Apesar da alta preval&#234;ncia, as arritmias supraventriculares (exceto FA) n&#227;o est&#227;o associadas a aumento da morbimortalidade.<xref ref-type="bibr" rid="B285"><sup>285</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B286"><sup>286</sup></xref> As EA e TSV n&#227;o sustentadas (dura&#231;&#227;o &lt; 30 segundos) s&#227;o pouco sintom&#225;ticas, notadas como palpita&#231;&#245;es, &#8220;cabe&#231;a leve&#8221;, tontura, batimentos no pesco&#231;o e &#8220;f&#244;lego curto&#8221;. Ocasionalmente, dispneia, dor tor&#225;cica e s&#237;ncope podem ocorrer, especialmente naqueles com arritmias agudas sustentadas, disfun&#231;&#227;o diast&#243;lica importante, EAo grave, IC ou DAC. Quanto maior a FC, menos tolerada &#233; a arritmia, em consequ&#234;ncia &#224; redu&#231;&#227;o do d&#233;bito card&#237;aco, que resulta nas manifesta&#231;&#245;es de isquemia cerebral e mioc&#225;rdica, hipotens&#227;o arterial e congest&#227;o pulmonar.<xref ref-type="bibr" rid="B287"><sup>287</sup></xref></p>
          <p>No idoso, algumas arritmias s&#227;o peculiares:<xref ref-type="bibr" rid="B288"><sup>288</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B289"><sup>289</sup></xref></p>
          <list list-type="alpha-lower">
            <list-item>
              <p>Taquicardia atrial com BAV: apresenta frequ&#234;ncia atrial r&#225;pida associada a resposta ventricular lenta devido a um BAV. A intoxica&#231;&#227;o digit&#225;lica e a hipocalemia s&#227;o causas comums.</p>
            </list-item>
            <list-item>
              <p>Taquicardia atrial multifocal: comum na presen&#231;a de DPOC.<xref ref-type="bibr" rid="B285"><sup>285</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B287"><sup>287</sup></xref> O tratamento &#233; direcionado &#224; doen&#231;a de base, considerada um ritmo pr&#233;-fibrilat&#243;rio.</p>
            </list-item>
            <list-item>
              <p>Ritmo juncional acelerado: intoxica&#231;&#227;o digit&#225;lica e IAM de parede inferior s&#227;o as causas mais comuns no idoso.<xref ref-type="bibr" rid="B285"><sup>285</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B287"><sup>287</sup></xref> O diagn&#243;stico &#233; sugerido por um ritmo regular bradic&#225;rdico, na presen&#231;a de FA.</p>
            </list-item>
            <list-item>
              <p><italic>Flutter</italic> atrial: habitualmente indica cardiopatia estrutural. Entre os idosos as causas mais comuns s&#227;o DAC e DPOC. Os idosos com flutter atrial t&#234;m maior chance de degenera&#231;&#227;o para FA, s&#227;o de alto risco para eventos tromboemb&#243;licos e devem receber abordagem semelhante aos casos de FA.</p>
            </list-item>
          </list>
          <p>Taquiarritmias ventriculares &#8211; As extrass&#237;stoles ventriculares s&#227;o comuns no idoso, com incid&#234;ncia de 70% a 90%.<xref ref-type="bibr" rid="B284"><sup>284</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B287"><sup>287</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B288"><sup>288</sup></xref> Em geral n&#227;o produzem sintomas, exceto quando muito frequentes. A sintomatologia &#233; variada, percebidas como batimentos repetitivos ou sensa&#231;&#227;o de que o &#8220;cora&#231;&#227;o vai parar&#8221;, devido &#224;s pausas compensat&#243;rias. S&#227;o associadas a risco de morte, na presen&#231;a de cardiopatia estrutural. Contudo, tratar a arritmia de forma isolada n&#227;o reduz o risco em idosos com DAC.<xref ref-type="bibr" rid="B286"><sup>286</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B289"><sup>289</sup></xref> Pr&#233;-s&#237;ncope, s&#237;ncope, baixo d&#233;bito, congest&#227;o pulmonar, dist&#250;rbio do comportamento e desorienta&#231;&#227;o s&#227;o manifesta&#231;&#245;es cl&#237;nicas de mau progn&#243;stico. Taquicardia ventricular (TV) frequentemente est&#225; associada a cardiopatia estrutural. HVE &#233; um importante determinante de arritmia ventricular,<xref ref-type="bibr" rid="B287"><sup>287</sup></xref> assim como a presen&#231;a de IC, que aumenta a incid&#234;ncia de TV de 2% a 4% naqueles sem IC para 20% a 80%.<xref ref-type="bibr" rid="B287"><sup>287</sup></xref> Nestes, a presen&#231;a de arritmia ventricular complexa est&#225; associada a aumento de mortalidade total, card&#237;aca e morte s&#250;bita. Quanto pior a disfun&#231;&#227;o ventricular, mais complexa e grave ser&#225; a arritmia ventricular. Assim, pacientes com disfun&#231;&#227;o ventricular esquerda ou HVE com arritmia ventricular complexa devem ser considerados de alto risco para morte s&#250;bita, mesmo assintom&#225;ticos. Em idosos sem cardiopatia o achado de taquiarritmias ao Holter n&#227;o apresenta implica&#231;&#227;o progn&#243;stica.<xref ref-type="bibr" rid="B286"><sup>286</sup></xref></p>
          <p>Com base nestas premissas, no que diz respeito &#224; avalia&#231;&#227;o diagn&#243;stica de taquiarritmias no paciente idoso esta diretriz recomenda:</p>
          <table-wrap id="t41">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="middle">Recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">Grau de recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Inqu&#233;rito sobre todas as medica&#231;&#245;es em uso e an&#225;lise do risco de indu&#231;&#227;o de arritmias ou prolongamento do QT</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">ECG de 12 deriva&#231;&#245;es em todos os pacientes a cada consulta, mesmo na aus&#234;ncia de sintomas</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">C&#225;lculo do intervalo QTc para todos os pacientes com queixa de palpita&#231;&#227;o</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">C&#225;lculo do intervalo QT para todos os pacientes com TV polim&#243;rfica</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Holter 24h para avalia&#231;&#227;o de sintomas de palpita&#231;&#227;o, s&#237;ncope e quedas inexplicadas no idoso</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Holter 24h para assintom&#225;ticos com fun&#231;&#227;o de VE normal e ECG com HVE</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Holter 24h para assintom&#225;ticos com fun&#231;&#227;o de VE deprimida e ECG com HVE</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Holter 24h para pacientes recuperados de FV/TV antes da alta hospitalar</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Holter 24h para pacientes recuperados de FV/TV durante o acompanhamento ambulatorial para avalia&#231;&#227;o de efic&#225;cia terap&#234;utica</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Holter 24h para pacientes assintom&#225;ticos com arritmia ventricular simples em exame inicial, com fun&#231;&#227;o VE normal e ECG com HVE, durante o acompanhamento ambulatorial para avalia&#231;&#227;o de efic&#225;cia terap&#234;utica</td>
                  <td align="center" valign="top">III</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Holter 24h para pacientes assintom&#225;ticos com arritmia ventricular complexa em exame inicial, com fun&#231;&#227;o VE normal e ECG com HVE, durante o acompanhamento ambulatorial para avalia&#231;&#227;o de efic&#225;cia terap&#234;utica</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Holter 24h para pacientes assintom&#225;ticos com arritmia ventricular simples em exame inicial, com fun&#231;&#227;o VE deprimida e ECG com HVE, durante o acompanhamento ambulatorial para avalia&#231;&#227;o de efic&#225;cia terap&#234;utica</td>
                  <td align="center" valign="top">III</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Holter 24h para pacientes assintom&#225;ticos com arritmia ventricular complexa em exame inicial, com fun&#231;&#227;o VE deprimida e ECG com HVE, durante o acompanhamento ambulatorial para avalia&#231;&#227;o de efic&#225;cia terap&#234;utica</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Holter 24h para assintom&#225;ticos com fun&#231;&#227;o de VE e ECG normais</td>
                  <td align="center" valign="top">III</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Teste ergom&#233;trico em pacientes sem contraindica&#231;&#227;o ao m&#233;todo e com palpita&#231;&#245;es induzidas pelo esfor&#231;o</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Teste ergom&#233;trico em pacientes sem contraindica&#231;&#227;o ao m&#233;todo e com palpita&#231;&#245;es associadas a angina do peito</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Teste ergom&#233;trico em pacientes sem contraindica&#231;&#227;o ao m&#233;todo, com palpita&#231;&#245;es de repouso</td>
                  <td align="center" valign="top">III</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Teste ergom&#233;trico em pacientes sem contraindica&#231;&#227;o ao m&#233;todo, assintom&#225;ticos, para investiga&#231;&#227;o de arritmia</td>
                  <td align="center" valign="top">III</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Ecocardiograma em todos os pacientes com palpita&#231;&#245;es</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Ecocardiograma em pacientes com HVE no ECG, assintom&#225;ticos</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Ecocardiograma em pacientes com palpita&#231;&#227;o e dispneia</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Ecocardiograma em pacientes com HVE e sopros card&#237;acos, assintom&#225;ticos</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Investiga&#231;&#227;o de etiologia isqu&#234;mica em todos os pacientes com taquicardia supraventricular</td>
                  <td align="center" valign="top">III</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Investiga&#231;&#227;o de etiologia isqu&#234;mica em todos os pacientes com taquicardia supraventricular e angina</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Investiga&#231;&#227;o de etiologia isqu&#234;mica em todos os pacientes com taquicardia ventricular complexa</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Resson&#226;ncia magn&#233;tica em pacientes com arritmia ventricular complexa e demais exames normais, na pesquisa de displasia arritmog&#234;nica do VD, fibrose mioc&#225;rdica e hipertrofia assim&#233;trica apical</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Resson&#226;ncia magn&#233;tica em todos os pacientes com TV</td>
                  <td align="center" valign="top">III</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Resson&#226;ncia magn&#233;tica em todos os pacientes com TSV</td>
                  <td align="center" valign="top">III</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">EEF em pacientes de alto risco de MS (s&#237;ncope inexplicada e arritmia ventricular complexa ao Holter ou bloqueio trifascular &#8211; para esclarecimento da etiologia da s&#237;ncope)</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN22a">
                <p><italic>ECG: eletrocardiograma; EEF: estudo eletrofisiol&#243;gico; FV: fibrila&#231;&#227;o ventricular; HVE: hipertrofia de ventr&#237;culo esquerdo; MS: morte s&#250;bita; TSV: taquiarritmia supraventricular; TV: taquicardia ventricular; VD: ventr&#237;culo direito; VE: ventr&#237;culo esquerdo</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>7.2.2. Peculiaridades no Tratamento</title>
          <p>Os princ&#237;pios do tratamento das taquiarritmias no idoso s&#227;o semelhantes aos dos mais jovens; contudo, mais frequentemente o tratamento &#233; influenciado pela presen&#231;a de cardiopatia de base como DAC, disfun&#231;&#227;o ventricular esquerda, HVE e comorbidades como insufici&#234;ncia renal cr&#244;nica (IRC) e DPOC.<xref ref-type="bibr" rid="B290"><sup>290</sup></xref> As arritmias atriais n&#227;o sustentadas (ESV e taquicardias atriais) em geral n&#227;o necessitam tratamento. Na maioria das vezes, est&#227;o associadas a doen&#231;a pulmonar de base e o tratamento desta, associado ao afastamento de estimulantes como cafe&#237;na, cigarro, refrigerantes, ch&#225;-preto e f&#225;rmacos beta-agonistas de a&#231;&#227;o r&#225;pida, costuma ser suficiente para a redu&#231;&#227;o do n&#250;mero de eventos e sintomas. Caso contr&#225;rio, o uso de bloqueadores dos canais de c&#225;lcio nos pacientes com DPOC (contraindicados se disfun&#231;&#227;o houver ventricular esquerda) ou betabloqueadores (em baixas doses e seletivos como bisoprolol ou metoprolol) naqueles sem contraindica&#231;&#227;o, pode ser indicado. As TPSV usualmente s&#227;o causadas por mecanismo reentrante e podem ser interrompidas por manobras vagais como manobra de Valsalva, tosse e v&#244;mito. A massagem do seio carot&#237;deo, devido ao risco de embolia arterial em pacientes com doen&#231;a carot&#237;dea significativa, deve ser evitada em idosos (exceto se exclu&#237;da sua presen&#231;a). Se as tentativas com manobras vagais falharem em reverter a arritmia, deve-se tentar a cardiovers&#227;o qu&#237;mica. O f&#225;rmaco de escolha inicial deve ser a adenosina, sob monitoramento eletrocardiogr&#225;fico. Em segunda linha est&#227;o os bloqueadores dos canais de c&#225;lcio (verapamil, diltiazem), se a fun&#231;&#227;o ventricular esquerda for normal, betabloqueadores, na presen&#231;a de DAC. Digoxina deve ser restrita aos pacientes com fun&#231;&#227;o ventricular deprimida. Nos casos irresponsivos aos agentes de primeira e segunda escolha, antiarr&#237;tmicos classe III (amiodarona ou sotalol) devem ser usados. Betabloqueadores e bloqueadores dos canais de c&#225;lcio s&#227;o igualmente eficazes em manter o RS e evitar recorr&#234;ncia da arritmia<xref ref-type="bibr" rid="B290"><sup>290</sup></xref> (<xref ref-type="table" rid="t42">Tabela 12</xref>). Se houver hipotens&#227;o, sinais de baixo fluxo cerebral, congest&#227;o pulmonar ou angina do peito, deve-se realizar cardiovers&#227;o el&#233;trica com 50 a 75J. A abla&#231;&#227;o por cateter para o tratamento da TPSV sustentada cujo mecanismo seja a reentrada nodal ou uma via access&#243;ria &#233; t&#227;o eficaz no idoso quanto nos jovens, com &#237;ndice de sucesso &gt; 95%.<xref ref-type="bibr" rid="B291"><sup>291</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B295"><sup>295</sup></xref> Idosos s&#227;o de maior risco de complica&#231;&#245;es como perfura&#231;&#227;o, les&#227;o vascular, insufici&#234;ncia renal, maior propens&#227;o a desenvolver FA e eventos tromboemb&#243;licos ap&#243;s o procedimento. Contudo, complica&#231;&#245;es maiores ocorrem em &lt; 3% dos idosos.<xref ref-type="bibr" rid="B292"><sup>292</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B293"><sup>293</sup></xref> Deve ser considerado como tratamento de escolha nos pacientes com epis&#243;dios frequentes (&gt; 2 eventos/ano, apesar do tratamento medicamentoso) ou naqueles em que haja contraindica&#231;&#227;o ao uso dos f&#225;rmacos anteriormente citados como bradicardia sinusal, hipotens&#227;o, broncospasmo, disfun&#231;&#227;o ventricular esquerda grave ou por op&#231;&#227;o do paciente de n&#227;o querer fazer o tratamento medicamentoso.</p>
          <table-wrap id="t42">
            <label>Tabela 12</label>
            <caption>
              <title>F&#225;rmacos de uso para tratamento das TPSV no idoso<xref ref-type="bibr" rid="B290"><sup>290</sup></xref></title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup width="16%">
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="center" valign="top" colspan="6">Cardiovers&#227;o na emerg&#234;ncia</th>
                </tr>
                <tr>
                  <th align="center" valign="top"/>
                  <th align="center" valign="top">F&#225;rmaco</th>
                  <th align="center" valign="top">Dose inicial</th>
                  <th align="center" valign="top">Repetir</th>
                  <th align="center" valign="top">Dose total</th>
                  <th align="center" valign="top">Precau&#231;&#245;es</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">1&#7491; escolha</td>
                  <td align="center" valign="top">Adenosina</td>
                  <td align="center" valign="top">6 mg IV em <italic>bolus</italic> r&#225;pido de 10 segundos</td>
                  <td align="center" valign="top">12 mg cada 15 minutos</td>
                  <td align="center" valign="top">30 mg</td>
                  <td align="center" valign="top">Pacientes com DAC e asma br&#244;nquica ativa</td>
                </tr>
                <tr>
                  <td align="left" valign="top">2&#7491; escolha</td>
                  <td align="center" valign="top">Verapamil</td>
                  <td align="center" valign="top">5 mg IV em 3 a 5 minutos</td>
                  <td align="center" valign="top">5 mg ap&#243;s 15 minutos</td>
                  <td align="center" valign="top">10 mg</td>
                  <td align="center" valign="top">Disfun&#231;&#227;o de VE e hipotens&#227;o</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Pacientes com disfun&#231;&#227;o grave do VE</td>
                  <td align="center" valign="top">Amiodarona</td>
                  <td align="center" valign="top">300 mg IV em 30 minutos dilu&#237;dos em soro fisiol&#243;gico a 0,9% ou Soro glicosado a 5% 100 a 250 mL</td>
                  <td align="center" valign="top">-</td>
                  <td align="center" valign="top">300 mg em <italic>bolus</italic> e 900 a 1.200 mg nas 24h subsequentes</td>
                  <td align="center" valign="top">Pode ser associada a digital IV para melhor controle da FC</td>
                </tr>
                <tr>
                  <td align="center" valign="top" colspan="6">
                    <bold>F&#225;rmacos para manuten&#231;&#227;o ap&#243;s revers&#227;o a ritmo sinusal</bold>
                  </td>
                </tr>
                <tr>
                  <td align="left" valign="top" rowspan="2">Bloqueadordos canais de c&#225;lcio</td>
                  <td align="center" valign="top">Diltiazem (iniciar com formula&#231;&#245;es de meia-vida curta), se tolerado, trocar por formula&#231;&#245;es de libera&#231;&#227;o prolongada, ap&#243;s o ajuste posol&#243;gico)</td>
                  <td align="center" valign="top">30 mg 3&#215;/dia</td>
                  <td align="center" valign="top">Aumentar a dose em 50% a cada 14 dias, se bem tolerado, at&#233; alcan&#231;ar FC desejada (60 a 70 bpm em repouso)</td>
                  <td align="center" valign="top">180 a 240 mg/dia</td>
                  <td align="center" valign="top">Cuidado com s&#237;ndrome taquicardia-bradicardia e disfun&#231;&#227;o de VE</td>
                </tr>
                <tr>
                  <td align="center" valign="top">Verapamil</td>
                  <td align="center" valign="top">120 mg/dia</td>
                  <td align="center" valign="top">Idem</td>
                  <td align="center" valign="top">240 mg/dia</td>
                  <td align="center" valign="top">Idem</td>
                </tr>
                <tr>
                  <td align="left" valign="top" rowspan="4">Betabloqueadores</td>
                  <td align="center" valign="top">Metoprolol</td>
                  <td align="center" valign="top">50 mg/dia</td>
                  <td align="center" valign="top"/>
                  <td align="center" valign="top"/>
                  <td align="center" valign="top">200 mg/dia</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Atenolol</td>
                  <td align="center" valign="top">25 mg/dia</td>
                  <td align="center" valign="top"/>
                  <td align="center" valign="top"/>
                  <td align="center" valign="top">200 mg/dia</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Propranolol (Nesta ordem de prefer&#234;ncia por conta da lipossolubilidade)</td>
                  <td align="center" valign="top">40 mg/dia</td>
                  <td align="center" valign="top"/>
                  <td align="center" valign="top">Dobrar a dose at&#233; alcan&#231;ar FC desejada de 60 a 70 bpm</td>
                  <td align="center" valign="top">240 mg/dia</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Carvedilol</td>
                  <td align="center" valign="top">3,125 mg 2&#215;/dia</td>
                  <td align="center" valign="top"/>
                  <td align="center" valign="top">Dobrar a dose cada 2 semanas</td>
                  <td align="center" valign="top">25 mg 2&#215;/dia</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Digoxina</td>
                  <td align="center" valign="top">Preferencial nos pacientes com IC</td>
                  <td align="center" valign="top">0,125 mg/dia</td>
                  <td align="center" valign="top">Cuidado com pacientes &gt; 75 anos e creatinina &gt; 1,5 mg/dL</td>
                  <td align="center" valign="top"/>
                  <td align="center" valign="top">0,25 mg/dia (nos pacientes mais idosos, debilitados ou com IRC, a dose deve ser titulada de acordo com a resposta e mantida em doses menores (at&#233; 0,125 mg 2 a 3&#215;/semana)</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Amiodarona</td>
                  <td align="center" valign="top">Aten&#231;&#227;o para efeitos colaterais, principalmente tiroidianos</td>
                  <td align="center" valign="top">600 mg/dia por 10 dias</td>
                  <td align="center" valign="top">Reduzir para 400 mg/dia por 10 dias e manter 200 mg/dia</td>
                  <td align="center" valign="top">Monitorar fun&#231;&#227;o hep&#225;tica, tiroidiana, intervalo QTc e fundo de olho cada 6 meses</td>
                  <td align="center" valign="top">Manter 100 a 200 mg/dia</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN11">
                <p><italic>DAC: doen&#231;a arterial coronariana; FC: frequ&#234;ncia card&#237;aca; IC: insufici&#234;ncia card&#237;aca; IRC: insufici&#234;ncia renal terminal; IV: via intravenosa; TPSV: taquicardia parox&#237;stica supraventricular; VE: ventr&#237;culo esquerdo</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>Recomenda&#231;&#245;es gerais &#8211; Tratamento das taquiarritmias no idoso: o tratamento das taquiarritmias em idosos deve ser semelhante ao dos pacientes mais jovens, principalmente naqueles entre 65 e 75 anos de idade. Naqueles &gt; 75 anos de idade, recomenda-se individualiza&#231;&#227;o da conduta com avalia&#231;&#227;o multiprofissional que considere n&#227;o s&#243; a idade, como comorbidades, fun&#231;&#227;o cognitiva, capacidade funcional, prefer&#234;ncias do paciente e gravidade dos sintomas.<xref ref-type="bibr" rid="B296"><sup>296</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B297"><sup>297</sup></xref></p>
        </sec>
      </sec>
      <sec>
        <title>7.3. Fibrila&#231;&#227;o Atrial</title>
        <sec>
          <title>7.3.1. Peculiaridades no Diagn&#243;stico</title>
          <p>A FA &#233; a arritmia persistente mais comum no idoso.<xref ref-type="bibr" rid="B298"><sup>298</sup></xref> Sua preval&#234;ncia e sua incid&#234;ncia dobram a cada d&#233;cada acima de 60 anos, chegando a acometer 8% a 10% dos pacientes &gt; 80 anos e 27% daqueles &gt; 90 anos de idade.<xref ref-type="bibr" rid="B287"><sup>287</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B301"><sup>301</sup></xref> Pode ocorrer isoladamente em consequ&#234;ncia das altera&#231;&#245;es morfol&#243;gicas e eletrofisiol&#243;gicas pr&#243;prias do envelhecimento no mioc&#225;rdio atrial e n&#243; sinusal &#8211; a chamada FA isolada ou <italic>lone atrial fibrillation</italic>. Contudo, a verdadeira FA isolada no idoso &#233; rara.<xref ref-type="bibr" rid="B302"><sup>302</sup></xref> Em geral, associa-se a cardiopatia estrutural: DAC, HAS, valvopatia mitral e IC.<xref ref-type="bibr" rid="B303"><sup>303</sup></xref> O hipertireoidismo subcl&#237;nico triplica o risco de FA.<xref ref-type="bibr" rid="B300"><sup>300</sup></xref> Aqueles com hipertireoidismo cl&#237;nico podem cursar com epis&#243;dios de FA parox&#237;stica. Outras causas de FA no idoso s&#227;o: a s&#237;ndrome da apneia-hipopneia obstrutiva do sono (comumente FA parox&#237;stica),<xref ref-type="bibr" rid="B303"><sup>303</sup></xref> a doen&#231;a do n&#243; sinusal e a miocardiopatia dilatada &#8211; estas em geral associadas a FA com baixa resposta ventricular. Especial aten&#231;&#227;o deve ser dada &#224; doen&#231;a do n&#243; sinusal representada pela s&#237;ndrome taquicardia-bradicardia, em que se observa FA parox&#237;stica recorrente com t&#233;rmino espont&#226;neo seguida de longa pausa ou mesmo assistolia, causa frequente de s&#237;ncope inexplicada no idoso. Ap&#243;s ajuste para DCV coexistentes, a mortalidade no paciente com FA &#233; 1,5 a 1,9 vez a de pacientes sem FA da mesma idade.<xref ref-type="bibr" rid="B299"><sup>299</sup></xref> A maior mortalidade deve-se primariamente ao aumento em 4 a 5 vezes na ocorr&#234;ncia de AVE, risco este que aumenta proporcionalmente com a idade ap&#243;s os 50 anos (&lt; 1,5% nos &lt; 50 anos e aproximadamente 23,5% nos pacientes &gt; 80 anos de idade).<xref ref-type="bibr" rid="B304"><sup>304</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B305"><sup>305</sup></xref> O diagn&#243;stico de FA no idoso &#233; realizado inicialmente por meio de exame f&#237;sico, anamnese e ECG. At&#233; 20% dos diagn&#243;sticos de FA no idoso ocorrem de forma casual, em consult&#243;rio, sem queixas, particularmente naqueles com FA permanente e resposta ventricular &lt; 100 bpm, que ocorre por conta de doen&#231;a nodal A-V concomitante ou uso de betabloqueador.<xref ref-type="bibr" rid="B287"><sup>287</sup></xref> Os sintomas mais frequentes no idoso s&#227;o: dispneia, astenia, tontura, fadiga f&#225;cil, diminui&#231;&#227;o da toler&#226;ncia ao exerc&#237;cio, sudorese, poli&#250;ria, s&#237;ncope e palpita&#231;&#227;o. A FA permanente est&#225; relacionada a eventos tromboemb&#243;licos silenciosos que, associados &#224; diminui&#231;&#227;o cr&#244;nica do fluxo cerebral e &#224;s altera&#231;&#245;es cerebrovasculares pr&#243;prias da idade, s&#227;o respons&#225;veis por d&#233;ficits cognitivos e motores inicialmente discretos, mas progressivos, como lentifica&#231;&#227;o, incoordena&#231;&#227;o motora e dem&#234;ncia, que podem passar despercebidos e retardar o diagn&#243;stico.<xref ref-type="bibr" rid="B306"><sup>306</sup></xref></p>
          <table-wrap id="t43">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top" colspan="3">Recomenda&#231;&#245;es gerais quanto ao diagn&#243;stico da FA no idoso</th>
                </tr>
                <tr>
                  <th align="left" valign="middle">Recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">Grau de recomenda&#231;&#227;o</th>
                  <th align="center" valign="top">N&#237;vel de evid&#234;ncia</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Inqu&#233;rito sobre todas as medica&#231;&#245;es em uso e an&#225;lise do risco de indu&#231;&#227;o de arritmias ou prolongamento do QT</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">ECG de 12 deriva&#231;&#245;es em todos os pacientes com ritmo irregular para diagn&#243;stico de FA, mesmo na aus&#234;ncia de sintomas</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">ECG de 12 deriva&#231;&#245;es em todos os pacientes com diagn&#243;stico de FA, a cada consulta</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Holter 24h para avalia&#231;&#227;o de controle da FC</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Holter 24h para acompanhamento ap&#243;s controle do ritmo, em assintom&#225;ticos</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Holter 24h para pacientes com queixa de palpita&#231;&#227;o e em ritmo sinusal ap&#243;s controle do ritmo</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Holter 24h para pacientes em ritmo sinusal, ap&#243;s AVE, para investiga&#231;&#227;o de FA parox&#237;stica</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Ecocardiograma transtor&#225;cico em todos os pacientes com FA, sem diagn&#243;stico pr&#233;vio de ICC</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Ecocardiograma transtor&#225;cico em todos os pacientes com FA</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Ecocardiograma transesog&#225;gico em pacientes com FA &gt; 48h, para revers&#227;o a RS</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Ecocardiograma transesof&#225;gico em pacientes com FA, ap&#243;s AVE para pesquisa de foco embolig&#234;nico</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN23a">
                <p><italic>AVE: acidente vascular encef&#225;lico; ECG: eletrocardiograma; FA: fibrila&#231;&#227;o atrial; FC: frequ&#234;ncia card&#237;aca; ICC: insufici&#234;ncia card&#237;aca congestiva; RS: ritmo sinusal</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>7.3.2. Peculiaridades no Tratamento</title>
          <p>O tratamento da FA em idosos n&#227;o difere do aplicado a pacientes jovens. A anticoagula&#231;&#227;o oral (salvo contraindica&#231;&#227;o) e a elimina&#231;&#227;o de fatores precipitantes ou revers&#237;veis da indu&#231;&#227;o de FA parox&#237;stica ou da perda de controle da frequ&#234;ncia ventricular nos pacientes com FA persistente ou permanente, constituem a base do tratamento da FA no idoso.<xref ref-type="bibr" rid="B307"><sup>307</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B308"><sup>308</sup></xref> A decis&#227;o pelo controle da FC ou do RS deve ser individualizada, por&#233;m como uma estrat&#233;gia inicial de rotina, n&#227;o h&#225; benef&#237;cio do controle do ritmo sobre o controle de FC em assintom&#225;ticos nessa faixa et&#225;ria.<xref ref-type="bibr" rid="B309"><sup>309</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B310"><sup>310</sup></xref></p>
          <sec>
            <title>7.3.2.1. Controle da Frequ&#234;ncia Card&#237;aca</title>
            <p>A estrat&#233;gia leniente de controle da FC (FC basal-alvo &lt; 110 bpm) &#233; t&#227;o eficaz para o controle de sintomas como o controle restrito de FC (FC de repouso-alvo &lt; 80 bpm), exceto em situa&#231;&#245;es de disfun&#231;&#227;o ventricular, com o cuidado de evitarem-se bradicardias significativas (FC &lt; 50 bpm).<xref ref-type="bibr" rid="B311"><sup>311</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B312"><sup>312</sup></xref> Os betabloqueadores isoladamente conseguem controle adequado da FC em 42% dos idosos<xref ref-type="bibr" rid="B312"><sup>312</sup></xref> e devem ser o f&#225;rmaco de escolha para este fim. A combina&#231;&#227;o com os bloqueadores dos canais de c&#225;lcio n&#227;o di-hidropirid&#237;nicos deve ser usada com precau&#231;&#227;o e apenas nos pacientes sem disfun&#231;&#227;o ventricular esquerda. Aten&#231;&#227;o para piora ou surgimento de constipa&#231;&#227;o com o seu uso, notadamente o verapamil, al&#233;m de bradicardia e edema de membros inferiores. A digoxina &#233; menos eficaz quando usada isoladamente no controle da FC durante o esfor&#231;o, sendo uma escolha aceit&#225;vel para pacientes fisicamente inativos, &gt; 80 anos de idade, naqueles em que outros tratamentos s&#227;o ineficazes ou contraindicados e com a devida cautela.<xref ref-type="bibr" rid="B311"><sup>311</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B313"><sup>313</sup></xref> Na s&#237;ndrome de taquicardia-bradicardia e naqueles que n&#227;o toleram o controle farmacol&#243;gico da FC, o implante de MP ou a abla&#231;&#227;o do n&#243; atrioventricular seguida de implante de MP pode ser indicado.<xref ref-type="bibr" rid="B314"><sup>314</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B315"><sup>315</sup></xref> O controle do ritmo deve ser reservado para circunst&#226;ncias espec&#237;ficas, em particular quando os sintomas n&#227;o podem ser contidos por meio do controle da FC, pois est&#225; relacionado a maior n&#250;mero de interna&#231;&#245;es em virtude de efeitos colaterais dos f&#225;rmacos antiarr&#237;tmicos (FAA) e a complica&#231;&#245;es dos procedimentos invasivos, principalmente na FA persistente de longa dura&#231;&#227;o. A estrat&#233;gia de controle do ritmo n&#227;o dispensa a anticoagula&#231;&#227;o.<xref ref-type="bibr" rid="B316"><sup>316</sup></xref> O controle pode ser feito por meio de FAA, cardiovers&#227;o el&#233;trica ou procedimentos intervencionistas. A cardiovers&#227;o el&#233;trica restaura o RS e est&#225; indicada nos quadros agudos de FA que n&#227;o respondem a terapia farmacol&#243;gica e que se apresentam com instabilidade hemodin&#226;mica. A base de escolha dos antiarr&#237;tmicos tanto para cardiovers&#227;o qu&#237;mica como para manuten&#231;&#227;o do ritmo depende da doen&#231;a card&#237;aca de base e das comorbidades, levando-se em considera&#231;&#227;o a ocorr&#234;ncia de maior efeito colateral dos mesmos, devido &#224; diminui&#231;&#227;o das fun&#231;&#245;es fisiol&#243;gicas e &#224; intera&#231;&#227;o com m&#250;ltiplas medica&#231;&#245;es simult&#226;neas comuns nos idosos. A propafenona, o sotalol e a amiodarona para pacientes com m&#237;nima ou nenhuma doen&#231;a card&#237;aca estrutural podem ser usadas, lembrando-se do maior risco de efeitos colaterais e proarr&#237;tmicos entre idosos com os dois primeiros. Para os pacientes com cardiopatia estrutural (HVE com septo interventricular &gt; 12 mm ou doen&#231;a coronariana) est&#225; indicado sotalol ou amiodarona. Reserva-se a amiodarona para idosos com IC e FEVE reduzida.<xref ref-type="bibr" rid="B317"><sup>317</sup></xref> A abla&#231;&#227;o por cateter pode ser &#250;til, com seguran&#231;a e efic&#225;cia aceit&#225;veis para idosos h&#237;gidos sintom&#225;ticos, sem muitas comorbidades, sem doen&#231;as card&#237;acas subjacentes, com paroxismos de FA, com refratariedade ao tratamento ou que n&#227;o desejem fazer uso de FAA e sem disfun&#231;&#227;o renal, realizadas em centros com grande experi&#234;ncia.<xref ref-type="bibr" rid="B318"><sup>318</sup></xref></p>
          </sec>
        </sec>
        <sec>
          <title>7.3.3. Anticoagula&#231;&#227;o Oral no Idoso com Fibrila&#231;&#227;o Atrial</title>
          <p>A complica&#231;&#227;o mais temida da FA &#233; o evento tromboemb&#243;lico, notadamente o AVE, cuja incid&#234;ncia e gravidade aumentam com a idade.<xref ref-type="bibr" rid="B319"><sup>319</sup></xref> &#201; a causa de at&#233; 25% dos AVE em idosos.<xref ref-type="bibr" rid="B320"><sup>320</sup></xref> A terapia de anticoagula&#231;&#227;o oral reduz em 64%o risco de ocorr&#234;ncia de AVE nos pacientes com FA n&#227;o valvar, superior &#224; aspirina, que reduz em apenas 22%, n&#227;o sendo esta mais recomendada para a preven&#231;&#227;o de AVE em FA.<xref ref-type="bibr" rid="B319"><sup>319</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B320"><sup>320</sup></xref> A dupla antiagrega&#231;&#227;o plaquet&#225;ria n&#227;o demonstrou benef&#237;cio para a preven&#231;&#227;o de eventos tromboemb&#243;licos em pacientes com FA e n&#227;o &#233; recomendada.<xref ref-type="bibr" rid="B321"><sup>321</sup></xref> O risco de tromboembolismo na FA pode ser calculado por meio de escores baseados em fatores de risco.<xref ref-type="bibr" rid="B322"><sup>322</sup></xref> Para avalia&#231;&#227;o do risco tromboemb&#243;lico, o escore Congestive Heart Failure, Hypertension, Age over 75 Years, Diabetes Mellitus, and a Previous Story of Stroke (CHADS<xref ref-type="bibr" rid="B2"><sup>2</sup></xref>) tem sido o mais usado e tem como vari&#225;veis a idade (&#8805; 75 anos) e a presen&#231;a de comorbidades (IC, HAS, diabetes melito e hist&#243;ria de tromboembolismo pr&#233;vio). Cada vari&#225;vel tem pontua&#231;&#227;o 1 e hist&#243;ria pr&#233;via de tromboembolismo, 2 pontos. Indica-se anticoagula&#231;&#227;o naqueles com pontua&#231;&#227;o &#8805; 2, por serem de alto risco de eventos.<xref ref-type="bibr" rid="B323"><sup>323</sup></xref> Em 2010, surgiu a proposta do CHA<sub>2</sub>DS<sub>2</sub>VASc considerando o maior risco do sexo feminino em idosos com 65 anos ou mais e a presen&#231;a de doen&#231;a arterial perif&#233;rica (1 ponto para cada uma das vari&#225;veis = IC, Hipertens&#227;o, idade de 65 a 74 anos, diabetes mellitus e doen&#231;a arterial perif&#233;rica; 2 pontos para idade de 75 anos ou mais e evento tromboemb&#243;lico pr&#233;vio), resultando em maior pontua&#231;&#227;o aos mais idosos, mulheres e portadores de doen&#231;a arterial perif&#233;rica. Esta diretriz, seguindo as recomenda&#231;&#245;es dos Guidelines<xref ref-type="bibr" rid="B324"><sup>324</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B325"><sup>325</sup></xref> mais recentes para o tratamento da FA, recomenda o uso do CHA<sub>2</sub>DS<sub>2</sub>VASc como escore cl&#237;nico para defini&#231;&#227;o do in&#237;cio da anticoagula&#231;&#227;o &#8211; homens com escore maior ou igual a 2 e mulheres com escore maior ou igual a 3. Nos pacientes de baixo risco (homens com escore 0 e mulheres com escore 1), recomendamos a utiliza&#231;&#227;o de par&#226;metros ecocardiogr&#225;ficos como aumento de AE e velocidade de fluxo de auriculeta, presen&#231;a de contrasta&#231;&#227;o espont&#226;nea moderada a acentuada ou trombo em auriculeta/AE como estratifica&#231;&#227;o adicional ao CHA<sub>2</sub>DS<sub>2</sub>VASc. Se presente qualquer destes achados, est&#225; indicada a anticoagula&#231;&#227;o.<xref ref-type="bibr" rid="B326"><sup>326</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B327"><sup>327</sup></xref> Ap&#243;s defini&#231;&#227;o do risco de evento tromboemb&#243;lico, faz-se necess&#225;ria a estratifica&#231;&#227;o quanto ao risco de sangramento, antes do in&#237;cio da terapia anticoagulante. O escore de risco para sangramento com anticoagula&#231;&#227;o mais empregado &#233; o HAS-BLED, cuja pontua&#231;&#227;o &gt; 3 indica maior risco de hemorragia pelo anticoagulante oral e inclui, al&#233;m da faixa et&#225;ria (idade &gt; 65 anos), vari&#225;veis como HAS com PAS &gt; 160 mmHg (1 ponto), disfun&#231;&#227;o renal ou hep&#225;tica (1 ponto cada), hist&#243;ria de AVE (1 ponto), sangramento (1 ponto), labilidade da INR (1 ponto) e uso de drogas ou &#225;lcool (1 ponto cada).<xref ref-type="bibr" rid="B328"><sup>328</sup></xref> Os dados sobre a influ&#234;ncia da idade isoladamente no risco de sangramento s&#227;o conflitantes, motivo pelo qual n&#227;o deve ser usada para contraindicar o in&#237;cio da anticoagula&#231;&#227;o.<xref ref-type="bibr" rid="B329"><sup>329</sup></xref> Os antagonistas da vitamina K, principalmente a varfarina, s&#227;o o pilar da anticoagula&#231;&#227;o oral em pacientes com FA, reduzindo significativamente o AVE e a mortalidade atribu&#237;da &#224; FA.<xref ref-type="bibr" rid="B330"><sup>330</sup></xref> A variabilidade da INR com o uso da varfarina depende n&#227;o somente da dosagem utilizada, mas, tamb&#233;m, da intera&#231;&#227;o com outras medica&#231;&#245;es e com certos tipos de alimentos.<xref ref-type="bibr" rid="B331"><sup>331</sup></xref> A labilidade da INR &#233; descrita em 21,3% dos pacientes de estudo observacional, de 40 a 89 anos de idade,<xref ref-type="bibr" rid="B328"><sup>328</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B329"><sup>329</sup></xref> segundo o qual o risco de INR &#8805; 5 aumenta em 15% a cada incremento de 10 anos. Deste maior risco, surge a necessidade de monitoramento mais regular e a menores intervalos da INR em idosos (especialmente naqueles &gt; 75 anos de idade) (grau de recomenda&#231;&#227;o I, n&#237;vel de evid&#234;ncia B). Esta diretriz recomenda o uso de baixa dose inicial para idosos &lt; 85 anos (3 a 4 mg) e 2,5 mg para idosos &#8805; 85 anos de idade, para aqueles com s&#237;ndrome de fragilidade, desnutri&#231;&#227;o ou doen&#231;a hep&#225;tica e insufici&#234;ncia renal moderada a avan&#231;ada (clearance de creatinina &lt; 30 mL/min). Primeira INR com 3 dias e nova dosagem com 7 dias, se houver ajuste da dose, e 14 dias, se a dose permanecer est&#225;vel. Semanal durante os primeiros 90 dias em pacientes de maior risco, quais sejam, aqueles &gt; 85 anos de idade, fr&#225;geis, com insufici&#234;ncia renal ou hep&#225;tica, hist&#243;rico de quedas, d&#233;ficit cognitivo, baixo n&#237;vel educacional e tratamento inicial. Nos demais, a avalia&#231;&#227;o da INR pode ser quinzenal nos primeiros 90 dias de tratamento e depois mensal, nos casos de INR est&#225;vel. Assim, &#233; segura a anticoagula&#231;&#227;o oral em idosos com varfarina, respeitados os cuidados na indica&#231;&#227;o e acompanhamento. A varfarina &#233; o anticoagulante oral de menor custo, cujo antagonista (a vitamina K), &#233; amplamente dispon&#237;vel para revers&#227;o do efeito anticoagulante do f&#225;rmaco.</p>
          <p>Recentemente, surgiram os anticoagulantes n&#227;o antagonistas da vitamina K, que t&#234;m as vantagens de n&#227;o necessitarem de monitoramento constante da coagula&#231;&#227;o sangu&#237;nea e apresentarem menos intera&#231;&#227;o medicamentosa. Dentre eles est&#227;o os inibidores diretos da trombina (dabigatrana) e os inibidores diretos do fator Xa (rivaroxabana, apixabana e edoxabana). Metan&#225;lise dos principais ensaios cl&#237;nicos randomizados com anticoagulantes n&#227;o antagonistas da vitamina K<xref ref-type="bibr" rid="B330"><sup>330</sup></xref> mostrou risco de AVE ou embolia sist&#234;mica significativamente menor do que com varfarina (risco relativo [RR] = 0,81, intervalo de confian&#231;a de 95% [IC 95%] = 0,73 a 0,91), assim como menor risco de sangramento intracraniano (RR = 0,48, IC 95% = 0,39 a 0,59), mas n&#227;o de sangramento maior (RR = 0,86, IC 95% = 0,73 a 1,00). Achados foram similares aos descritos em segunda metan&#225;lise<xref ref-type="bibr" rid="B331"><sup>331</sup></xref> com participantes &#8805; 75 anos de idade. Apesar do claro benef&#237;cio dos anticoagulantes n&#227;o antagonistas da vitamina K e de estes serem mais seguros quanto ao sangramento intracraniano, as taxas desta complica&#231;&#227;o s&#227;o relativamente baixas (&lt; 1%/ano), mesmo com varfarina (0,76% a 0,85% com varfarina e 0,26% a 0,49% com n&#227;o antagonistas).<xref ref-type="bibr" rid="B331"><sup>331</sup></xref> Os novos anticoagulantes orais, portanto, s&#227;o a op&#231;&#227;o de anticoagula&#231;&#227;o mais segura em idosos com maior risco de sangramento, nos pacientes com dificuldade de ades&#227;o ao monitoramento da INR, em uso de m&#250;ltiplas medica&#231;&#245;es ou por op&#231;&#227;o individual, devendo, contudo, ter suas doses ajustadas &#224; fun&#231;&#227;o renal e idade (&lt; ou &gt; 75 anos)<xref ref-type="bibr" rid="B330"><sup>330</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B331"><sup>331</sup></xref> (grau de recomenda&#231;&#227;o I, n&#237;vel de evid&#234;ncia B). At&#233; recentemente havia preocupa&#231;&#245;es devido &#224; falta de ant&#237;doto espec&#237;fico para revers&#227;o dos efeitos anticoagulantes dos n&#227;o antagonistas da vitamina K, entretanto, houve a introdu&#231;&#227;o do idarucizumabe, recentemente licenciado para uso em humanos, para revers&#227;o dos efeitos da dabigatrana.<xref ref-type="bibr" rid="B332"><sup>332</sup></xref></p>
          <table-wrap id="t44">
            <table frame="hsides" rules="groups">
              <colgroup width="20%">
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top" colspan="5">Doses recomendadas para idosos</th>
                </tr>
                <tr>
                  <th align="center" valign="top"/>
                  <th align="center" valign="top">Dabigatrana</th>
                  <th align="center" valign="top">Rivaroxabana</th>
                  <th align="center" valign="top">Apixabana</th>
                  <th align="center" valign="top">Endoxabana</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Apresenta&#231;&#227;o comercial</td>
                  <td align="center" valign="top">150 mg 110 mg</td>
                  <td align="center" valign="top">20 mg 15 mg 10 mg</td>
                  <td align="center" valign="top">5 mg 2,5 mg</td>
                  <td align="center" valign="top">30 mg 60 mg</td>
                </tr>
                <tr>
                  <td align="left" valign="top" rowspan="2">Dose</td>
                  <td align="center" valign="top">150 mg Cl Cr &gt; 50 ml/min</td>
                  <td align="center" valign="top">20 mg Cl Cr &gt; 50 ml/min</td>
                  <td align="center" valign="top">5 mg Cl Cr &gt; 30 ml/min</td>
                  <td align="center" valign="top">60 mg Cl Cr &gt; 50 ml/min</td>
                </tr>
                <tr>
                  <td align="left" valign="top">110 mg Cl Cr entre 30 e 50 ml/min</td>
                  <td align="center" valign="top">15 mg Cl Cr entre 30 e 50 ml/min</td>
                  <td align="center" valign="top">2,5 mg Cl Cr 15-30 ml/min ou Dois dos crit&#233;rios abaixo: &#8805; 80 anos Peso &#8804; 60 kg Creatinina &#8805; 1,5 mg</td>
                  <td align="center" valign="top">30 mg Cl Cr 15-50 ml/min ou peso &#8804; 60 Kg</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Posologia</td>
                  <td align="center" valign="top">2 x ao dia</td>
                  <td align="center" valign="top">1 x dia</td>
                  <td align="center" valign="top">2 x dia</td>
                  <td align="center" valign="top">1 x dia</td>
                </tr>
                <tr>
                  <td align="left" valign="top" rowspan="2">Particularidades</td>
                  <td align="center" valign="top">Comum dispepsia</td>
                  <td align="center" valign="top">Maior risco de sangramento GI que warfarina</td>
                  <td align="center" valign="top"/>
                  <td align="center" valign="top"/>
                </tr>
                <tr>
                  <td align="center" valign="top">Evitar se Cl Cr &lt; 30 ml/min), AVC recente e doen&#231;a hep&#225;tica grave ativa</td>
                  <td align="center" valign="top">Evitar se Cl Cr &lt; 15 ml/min) e doen&#231;a hep&#225;tica grave ativa</td>
                  <td align="center" valign="top">Evitar se Cl Cr &lt; 15 ml/min) ou Creatinina &gt; 2,5 mg e doen&#231;a hep&#225;tica grave ativa</td>
                  <td align="center" valign="top">Evitar se Cl Cr &lt; 15 ml/min ou doen&#231;a hep&#225;tica grave.</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN24a">
                <p>
                  <italic>AVC: acidente vascular cerebral; ClCr: clearance de creatinina; GI: gastrintestinal. Fonte: European Heart Journal.</italic>
                  <xref ref-type="bibr" rid="B324">
                    <sup>324</sup>
                  </xref>
                </p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <sec>
            <title>7.3.3.1. Recomenda&#231;&#245;es Gerais</title>
            <list list-type="order">
              <list-item>
                <p>Exceto se contraindica&#231;&#227;o formal &#224; anticoagula&#231;&#227;o, os idosos com FA devem ser anticoagulados, se CHADS<sub>2</sub>VASC<sub>2</sub> &#8805; 2 para homens e &#8805; 3 para mulheres (grau de recomenda&#231;&#227;o I, n&#237;vel de evid&#234;ncia A).<xref ref-type="bibr" rid="B324"><sup>324</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B325"><sup>325</sup></xref> Se CHADS<sub>2</sub>VASC<sub>2</sub> &lt; 2 para homens ou &lt; 3 para mulheres, avaliar tamanho do AE &gt; 5,0 cm (ou &#225;rea indexada pela superf&#237;cie corp&#243;rea &gt; 30 mm/m<sup>2</sup>) ao ecocardiograma transtor&#225;cico tamb&#233;m devem ter iniciada a anticoagula&#231;&#227;o (grau de recomenda&#231;&#227;o IIa, n&#237;vel de evid&#234;ncia B). Idosos com idade &lt; 65 anos, com CHADS<sub>2</sub>VASC<sub>2</sub> = 0 para homens ou 1 para mulheres s&#243; devem ser anticoagulados se AE &gt; 5,0 cm, presen&#231;a de contraste espont&#226;neo moderado a severo ou trombo ao ecocardiograma transesof&#225;gico (grau de recomenda&#231;&#227;o IIa, n&#237;vel de evid&#234;ncia B).</p>
              </list-item>
              <list-item>
                <p>O escore de risco para sangramento com anticoagula&#231;&#227;o recomendado &#233; o HAS-BLED (grau de recomenda&#231;&#227;o I, n&#237;vel de evid&#234;ncia B). S&#227;o considerados de maior risco os idosos &gt; 85 anos, fr&#225;geis, com insufici&#234;ncia renal ou hep&#225;tica, portadores de d&#233;ficit cognitivo moderado a grave, baixo n&#237;vel educacional e durante os primerios 90 dias de tratamento com anticoagulantes. Recomendam-se anticoagula&#231;&#227;o com ajuste da dose e acompanhamento mais regular nestes pacientes, por&#233;m n&#227;o deve ser contraindicada (grau de recomenda&#231;&#227;o I, n&#237;vel de evid&#234;ncia C).</p>
              </list-item>
              <list-item>
                <p>Em paralelo, o controle da HAS e do risco de quedas pode adicionalmente reduzir o risco de complica&#231;&#245;es hemorr&#225;gicas, assim como a aten&#231;&#227;o quando da introdu&#231;&#227;o de novos f&#225;rmacos em associa&#231;&#227;o como antiplaquet&#225;rios e antibi&#243;ticos que possam interferir nos n&#237;veis s&#233;ricos ou potencializar o risco de sangramento.</p>
              </list-item>
              <list-item>
                <p>Em usu&#225;rios de varfarina, recomenda-se a dosagem de INR 5 a 7 dias ap&#243;s o in&#237;cio de antibioticoterapia (grau de recomenda&#231;&#227;o I, n&#237;vel de evid&#234;ncia C).</p>
              </list-item>
              <list-item>
                <p>Quanto a escolha do anticoagulante, as evidencias atuais demonstram que os anticoagulantes inibidores diretos orais (DOAC) s&#227;o preferidos sobre a varfarina, exceto para pacientes com EM moderada a grave e portadores de pr&#243;tese valvar (grau de recomenda&#231;&#227;o I, n&#237;vel de evid&#234;ncia A).<xref ref-type="bibr" rid="B324"><sup>324</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B325"><sup>325</sup></xref> No entanto, essa diretriz tamb&#233;m recomenda o uso da varfarina, em situa&#231;&#245;es de disponibilidade ou prefer&#234;ncia, pelo fato de ser um f&#225;rmaco oral, conhecido, de baixo custo e amplo acesso aos pacientes da rede p&#250;blica no Brasil, al&#233;m de possuir um antagonista (a vitamina K) dispon&#237;vel para revers&#227;o de seu efeito anticoagulante (grau de recomenda&#231;&#227;o I, n&#237;vel de evid&#234;ncia A).</p>
              </list-item>
              <list-item>
                <p>Os DOAC s&#227;o op&#231;&#227;o de anticoagula&#231;&#227;o segura em idosos com maior risco de sangramento, nos pacientes com dificuldade de ades&#227;o &#224; monitoriza&#231;&#227;o do INR, em uso de m&#250;ltiplas medica&#231;&#245;es ou por op&#231;&#227;o individual, devendo, contudo, terem suas doses ajustadas &#224; fun&#231;&#227;o renal e idade<xref ref-type="bibr" rid="B330"><sup>330</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B331"><sup>331</sup></xref> (grau de recomenda&#231;&#227;o I, n&#237;vel de evid&#234;ncia A). Dentre estes, o rivaroxaban e o edoxaban s&#227;o os DOAC de escolha por sua praticidade de uso (uma vez ao dia). Nos pacientes com dispepsia, evitar o dabigatran. (grau de recomenda&#231;&#227;o I, n&#237;vel de evid&#234;ncia B). Nenhum dos DOAC foram testados na insufici&#234;ncia renal grave,<xref ref-type="bibr" rid="B324"><sup>324</sup></xref> desta forma esta Diretriz n&#227;o recomenda seu uso em pacientes com clearance de creatinina &lt; 30 ml/min, nestes preferir a varfarina (grau de recomenda&#231;&#227;o I, n&#237;vel de evid&#234;ncia B).</p>
              </list-item>
            </list>
            <boxed-text>
              <p>
                <bold>Errata</bold>
              </p>
              <p>Edi&#231;&#227;o de Maio de 2019, vol. 112 (5), p&#225;gs. 649-705</p>
              <p>Na &#8220;Atualiza&#231;&#227;o das Diretrizes em Cardiogeriatria da Sociedade Brasileira de Cardiologia 2019&#8221;, com n&#250;mero de DOI: <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.5935/abc.20190086">https://doi.org/10.5935/abc.20190086</ext-link>, publicado no peri&#243;dico Arquivos Brasileiros de Cardiologia, 112(5):649-705, foi inclu&#237;do o nome do autor Felipe Costa Fuchs na p&#225;g. 649, entre os autores do cap&#237;tulo 6; na p&#225;g. 650, entre os autores da atualiza&#231;&#227;o; e na p&#225;g. 652, na declara&#231;&#227;o de conflito de interesse.</p>
            </boxed-text>
          </sec>
        </sec>
      </sec>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="other" id="fn1">
        <p>
          <bold>Realiza&#231;&#227;o:</bold>
        </p>
        <p>Departamento de Cardiogeriatria da Sociedade Brasileira da Cardiologia e Sociedade Brasileira de Geriatria e Gerontologia</p>
      </fn>
      <fn fn-type="other" id="fn2">
        <p>
          <bold>Conselho de Normatiza&#231;&#245;es e Diretrizes:</bold>
        </p>
        <p>Bacal, Leandro Ioschpe Zimerman, Paulo Ricardo Avancini Caramori e Pedro A. Lemos</p>
      </fn>
      <fn fn-type="other" id="fn3">
        <p>
          <bold>Coordenador de Normatiza&#231;&#245;es e Diretrizes:</bold>
        </p>
        <p>Ludhmila Abrah&#227;o Hajjar</p>
      </fn>
      <fn fn-type="other" id="fn4">
        <p>
          <bold>Editores:</bold>
        </p>
        <p>Gilson Soares Feitosa-Filho, Jos&#233; Maria Peixoto, Jos&#233; Elias Soares Pinheiro</p>
      </fn>
      <fn fn-type="other" id="fn5">
        <p>
          <bold>Esta atualiza&#231;&#227;o dever&#225; ser citada como:</bold>
        </p>
        <p>Feitosa-Filho GS, Peixoto JM, Pinheiro JES, Afiune Neto A, Albuquerque ALT, Cattani AC et al. Atualiza&#231;&#227;o das Diretrizes em Cardiogeriatria da Sociedade Brasileira de Cardiologia. Arq Bras Cardiol. 2019; 112(5):649-705.</p>
      </fn>
      <fn fn-type="other" id="fn7">
        <label>Errata</label>
        <p>
          <bold>Edi&#231;&#227;o de Maio de 2019, vol. 112 (5), p&#225;gs. 649-705</bold>
        </p>
        <p>Na &#8220;Atualiza&#231;&#227;o das Diretrizes em Cardiogeriatria da Sociedade Brasileira de Cardiologia &#8211; 2019&#8221;, com n&#250;mero de DOI: <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.5935/abc.20190086">https://doi.org/10.5935/abc.20190086</ext-link>, publicado no peri&#243;dico Arquivos Brasileiros de Cardiologia, 112(5):649-705, foi inclu&#237;do o nome do autor Felipe Costa Fuchs na p&#225;g. 649, entre os autores do cap&#237;tulo 6; na p&#225;g. 650, entre os autores da atualiza&#231;&#227;o; e na p&#225;g. 652, na declara&#231;&#227;o de conflito de interesse.</p>
      </fn>
    </fn-group>
    <ref-list>
      <title>Refer&#234;ncias</title>
      <ref id="B1">
        <label>1</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <collab>Instituto Brasileiro de Geografia e Estat&#237;stica. (IBGE)</collab>
          </person-group>
          <source>Pesquisa Nacional de Sa&#250;de (PNS)</source>
          <publisher-loc>Rio de Janeiro</publisher-loc>
          <year>2013</year>
        </element-citation>
        <mixed-citation>1. Instituto Brasileiro de Geografia e Estat&#237;stica. (IBGE). Pesquisa Nacional de Sa&#250;de (PNS). Rio de Janeiro; 2013.</mixed-citation>
      </ref>
      <ref id="B2">
        <label>2</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <collab>Brasil</collab>
          </person-group>
          <source>Minist&#233;rio da Sa&#250;de</source>
          <publisher-name>Sistema de informa&#231;&#227;o sobre a mortalidade</publisher-name>
          <publisher-loc>Bras&#237;lia</publisher-loc>
          <year>2013</year>
        </element-citation>
        <mixed-citation>2. Brasil. Minist&#233;rio da Sa&#250;de. Sistema de informa&#231;&#227;o sobre a mortalidade. Bras&#237;lia; 2013.</mixed-citation>
      </ref>
      <ref id="B3">
        <label>3</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Fried</surname>
              <given-names>LP</given-names>
            </name>
            <name>
              <surname>Tangen</surname>
              <given-names>CM</given-names>
            </name>
            <name>
              <surname>Walston</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Newman</surname>
              <given-names>AB</given-names>
            </name>
            <name>
              <surname>Hirsch</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Gottdiener</surname>
              <given-names>J</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Frailty in older adults evidence for a phenotype</article-title>
          <source>J Gerontol A Biol Sci Med Sci</source>
          <year>2001</year>
          <volume>56</volume>
          <issue>3</issue>
          <fpage>M146</fpage>
          <lpage>M156</lpage>
        </element-citation>
        <mixed-citation>3. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J et al. Frailty in older adults evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146-56.</mixed-citation>
      </ref>
      <ref id="B4">
        <label>4</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Fried</surname>
              <given-names>LP</given-names>
            </name>
            <name>
              <surname>Ferrucci</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Darer</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Williamson</surname>
              <given-names>JD</given-names>
            </name>
            <name>
              <surname>Anderson</surname>
              <given-names>G</given-names>
            </name>
          </person-group>
          <article-title>Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care</article-title>
          <source>J Gerontol A Biol Sci Med Sci</source>
          <year>2004</year>
          <volume>59</volume>
          <issue>3</issue>
          <fpage>255</fpage>
          <lpage>263</lpage>
        </element-citation>
        <mixed-citation>4. Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol A Biol Sci Med Sci. 2004;59(3):255-63.</mixed-citation>
      </ref>
      <ref id="B5">
        <label>5</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Morley</surname>
              <given-names>JE</given-names>
            </name>
            <name>
              <surname>Vellas</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>van Kan</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Anker</surname>
              <given-names>SD</given-names>
            </name>
            <name>
              <surname>Bauer</surname>
              <given-names>JM</given-names>
            </name>
            <name>
              <surname>Bernabei</surname>
              <given-names>R</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Frailty consensus: a call to action</article-title>
          <source>J Am Med Dir Assoc</source>
          <year>2013</year>
          <volume>14</volume>
          <issue>6</issue>
          <fpage>392</fpage>
          <lpage>397</lpage>
        </element-citation>
        <mixed-citation>5. Morley JE, Vellas B, van Kan A, Anker SD, Bauer JM, Bernabei R et al. Frailty consensus: a call to action. J Am Med Dir Assoc. 2013;14(6):392-7.</mixed-citation>
      </ref>
      <ref id="B6">
        <label>6</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Collard</surname>
              <given-names>RM</given-names>
            </name>
            <name>
              <surname>Boter</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Schoevers</surname>
              <given-names>RA</given-names>
            </name>
            <name>
              <surname>Oude Voshaar</surname>
              <given-names>RC</given-names>
            </name>
          </person-group>
          <article-title>Prevalence of frailty in community-dwelling older persons: a systematic review</article-title>
          <source>J Am Geriatr Soc</source>
          <year>2012</year>
          <volume>60</volume>
          <issue>8</issue>
          <fpage>1487</fpage>
          <lpage>1492</lpage>
        </element-citation>
        <mixed-citation>6. Collard RM, Boter H, Schoevers RA, Oude Voshaar RC. Prevalence of frailty in community-dwelling older persons: a systematic review. J Am Geriatr Soc. 2012;60(8):1487-92.</mixed-citation>
      </ref>
      <ref id="B7">
        <label>7</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Afilalo</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Alexander</surname>
              <given-names>KP</given-names>
            </name>
            <name>
              <surname>Mack</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Maurer</surname>
              <given-names>MS</given-names>
            </name>
            <name>
              <surname>Green</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Allen</surname>
              <given-names>LA</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Frailty assessment in the cardiovascular care of older adults</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2014</year>
          <volume>63</volume>
          <issue>8</issue>
          <fpage>747</fpage>
          <lpage>762</lpage>
        </element-citation>
        <mixed-citation>7. Afilalo J, Alexander KP, Mack MJ, Maurer MS, Green P, Allen LA et al. Frailty assessment in the cardiovascular care of older adults. J Am Coll Cardiol. 2014;63(8):747-62.</mixed-citation>
      </ref>
      <ref id="B8">
        <label>8</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Puts</surname>
              <given-names>MT</given-names>
            </name>
            <name>
              <surname>Toubasi</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Andrew</surname>
              <given-names>MK</given-names>
            </name>
            <name>
              <surname>Ashe</surname>
              <given-names>MC</given-names>
            </name>
            <name>
              <surname>Ploeg</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Atkinson</surname>
              <given-names>E</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Interventions to prevent or reduce the level of frailty in community-dwelling older adults: a scoping review of the literature and international policies</article-title>
          <source>Age Ageing</source>
          <year>2017</year>
          <volume>46</volume>
          <issue>3</issue>
          <fpage>383</fpage>
          <lpage>392</lpage>
        </element-citation>
        <mixed-citation>8. Puts MT, Toubasi S, Andrew MK, Ashe MC, Ploeg J, Atkinson E et al. Interventions to prevent or reduce the level of frailty in community-dwelling older adults: a scoping review of the literature and international policies. Age Ageing. 2017;46(3):383-92.</mixed-citation>
      </ref>
      <ref id="B9">
        <label>9</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Rockwood</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Mitnitski</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
          <article-title>Frailty in relation to the accumulation of deficits</article-title>
          <source>J Gerontol A Biol Sci Med Sci</source>
          <year>2007</year>
          <volume>62</volume>
          <issue>7</issue>
          <fpage>722</fpage>
          <lpage>727</lpage>
        </element-citation>
        <mixed-citation>9. Rockwood K, Mitnitski A. Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci. 2007;62(7):722-7.</mixed-citation>
      </ref>
      <ref id="B10">
        <label>10</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Demougeot</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>van Kan</surname>
              <given-names>GA</given-names>
            </name>
            <name>
              <surname>Vellas</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>de Souto Barreto</surname>
              <given-names>P</given-names>
            </name>
          </person-group>
          <article-title>Frailty detection with the G&#233;rontop&#244;le Frailty Screening Tool (GFST)</article-title>
          <source>J Frailty Aging</source>
          <year>2013</year>
          <volume>2</volume>
          <issue>3</issue>
          <fpage>150</fpage>
          <lpage>152</lpage>
        </element-citation>
        <mixed-citation>10. Demougeot L, van Kan GA, Vellas B, de Souto Barreto P. Frailty detection with the G&#233;rontop&#244;le Frailty Screening Tool (GFST). J Frailty Aging. 2013;2(3):150-2.</mixed-citation>
      </ref>
      <ref id="B11">
        <label>11</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Abellan van Kan</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Rolland</surname>
              <given-names>YM</given-names>
            </name>
            <name>
              <surname>Morley</surname>
              <given-names>JE</given-names>
            </name>
            <name>
              <surname>Vellas</surname>
              <given-names>B</given-names>
            </name>
          </person-group>
          <article-title>Frailty: toward a clinical definition</article-title>
          <source>J Am Med Dir Assoc</source>
          <year>2008</year>
          <volume>9</volume>
          <issue>2</issue>
          <fpage>71</fpage>
          <lpage>72</lpage>
        </element-citation>
        <mixed-citation>11. Abellan van Kan G, Rolland YM, Morley JE, Vellas B. Frailty: toward a clinical definition. J Am Med Dir Assoc. 2008;9(2):71-2.</mixed-citation>
      </ref>
      <ref id="B12">
        <label>12</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Steverink</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Slaets</surname>
              <given-names>JPJ</given-names>
            </name>
            <name>
              <surname>Schuurmans</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>van Lis</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
          <article-title>Measuring frailty. development and testing of the Groningen Frailty Indicator (GFI)</article-title>
          <source>Gerontologist</source>
          <year>2001</year>
          <volume>41</volume>
          <fpage>236</fpage>
          <lpage>237</lpage>
        </element-citation>
        <mixed-citation>12. Steverink N, Slaets JPJ, Schuurmans H, van Lis M. Measuring frailty. development and testing of the Groningen Frailty Indicator (GFI). Gerontologist. 2001;41:236-7.</mixed-citation>
      </ref>
      <ref id="B13">
        <label>13</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Santiago</surname>
              <given-names>LM</given-names>
            </name>
            <name>
              <surname>Luz</surname>
              <given-names>LL</given-names>
            </name>
            <name>
              <surname>Mattos</surname>
              <given-names>IE</given-names>
            </name>
            <name>
              <surname>Gobbens</surname>
              <given-names>RJ</given-names>
            </name>
          </person-group>
          <article-title>Adapta&#231;&#227;o transcultural do instrumento Tilburg Frailty Indicator (TFI) para a popula&#231;&#227;o brasileira</article-title>
          <source>Cad Sa&#250;de P&#250;blica</source>
          <year>2012</year>
          <volume>28</volume>
          <issue>9</issue>
          <fpage>1795</fpage>
          <lpage>1801</lpage>
        </element-citation>
        <mixed-citation>13. Santiago LM, Luz LL, Mattos IE, Gobbens RJ. Adapta&#231;&#227;o transcultural do instrumento Tilburg Frailty Indicator (TFI) para a popula&#231;&#227;o brasileira. Cad Sa&#250;de P&#250;blica. 2012;28(9):1795-801.</mixed-citation>
      </ref>
      <ref id="B14">
        <label>14</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ra&#238;che</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>H&#233;bert</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Dubois</surname>
              <given-names>MF</given-names>
            </name>
          </person-group>
          <article-title>PRISMA-7: a case-finding tool to identify older adults with moderate to severe disabilities</article-title>
          <source>Arch Gerontol Geriatr</source>
          <year>2008</year>
          <volume>47</volume>
          <issue>1</issue>
          <fpage>9</fpage>
          <lpage>18</lpage>
        </element-citation>
        <mixed-citation>14. Ra&#238;che M, H&#233;bert R, Dubois MF. PRISMA-7: a case-finding tool to identify older adults with moderate to severe disabilities. Arch Gerontol Geriatr. 2008;47(1):9-18.</mixed-citation>
      </ref>
      <ref id="B15">
        <label>15</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Saliba</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Elliott</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Rubenstein</surname>
              <given-names>LZ</given-names>
            </name>
            <name>
              <surname>Solomon</surname>
              <given-names>DH</given-names>
            </name>
            <name>
              <surname>Young</surname>
              <given-names>RT</given-names>
            </name>
            <name>
              <surname>Kamberg</surname>
              <given-names>CJ</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>The Vulnerable Elders Survey: a tool for identifying vulnerable older people in the community</article-title>
          <source>J Am Geriatr Soc</source>
          <year>2001</year>
          <volume>49</volume>
          <issue>12</issue>
          <fpage>1691</fpage>
          <lpage>1699</lpage>
        </element-citation>
        <mixed-citation>15. Saliba D, Elliott M, Rubenstein LZ, Solomon DH, Young RT, Kamberg CJ et al. The Vulnerable Elders Survey: a tool for identifying vulnerable older people in the community. J Am Geriatr Soc. 2001;49(12):1691-9.</mixed-citation>
      </ref>
      <ref id="B16">
        <label>16</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Fabr&#237;cio-Wehbe</surname>
              <given-names>SC</given-names>
            </name>
            <name>
              <surname>Cruz</surname>
              <given-names>IR</given-names>
            </name>
            <name>
              <surname>Haas</surname>
              <given-names>VJ</given-names>
            </name>
            <name>
              <surname>Diniz</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Dantas</surname>
              <given-names>RA</given-names>
            </name>
            <name>
              <surname>Rodrigues</surname>
              <given-names>RA</given-names>
            </name>
          </person-group>
          <article-title>Adapta&#231;&#227;o cultural e validade da Edmonton Frail Scale - EFS em uma amostra de idosos brasileiros</article-title>
          <source>Rev Lat Am Enferm</source>
          <year>2009</year>
          <volume>17</volume>
          <issue>6</issue>
          <fpage>1330</fpage>
          <lpage>1336</lpage>
        </element-citation>
        <mixed-citation>16. Fabr&#237;cio-Wehbe SC, Cruz IR, Haas VJ, Diniz MA, Dantas RA, Rodrigues RA. Adapta&#231;&#227;o cultural e validade da Edmonton Frail Scale - EFS em uma amostra de idosos brasileiros. Rev Lat Am Enferm. 2009;17(6):1330-6.</mixed-citation>
      </ref>
      <ref id="B17">
        <label>17</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Chen</surname>
              <given-names>MA</given-names>
            </name>
          </person-group>
          <article-title>Frailty and cardiovascular disease: potential role of gait speed in surgical risk stratification in older adults</article-title>
          <source>J Geriatr Cardiol</source>
          <year>2015</year>
          <volume>12</volume>
          <issue>1</issue>
          <fpage>44</fpage>
          <lpage>56</lpage>
        </element-citation>
        <mixed-citation>17. Chen MA. Frailty and cardiovascular disease: potential role of gait speed in surgical risk stratification in older adults. J Geriatr Cardiol. 2015;12(1):44-56.</mixed-citation>
      </ref>
      <ref id="B18">
        <label>18</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Alfredsson</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Stebbins</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Brennan</surname>
              <given-names>JM</given-names>
            </name>
            <name>
              <surname>Matsouaka</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Afilalo</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Peterson</surname>
              <given-names>ED</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Gait speed predicts 30-day mortality after transcatheter aortic valve replacement: results from the Society of Thoracic Surgeons / American College of Cardiology Transcatheter Valve Therapy Registry</article-title>
          <source>Circulation</source>
          <year>2016</year>
          <volume>133</volume>
          <issue>14</issue>
          <fpage>1351</fpage>
          <lpage>1359</lpage>
        </element-citation>
        <mixed-citation>18. Alfredsson J, Stebbins A, Brennan JM, Matsouaka R, Afilalo J, Peterson ED et al. Gait speed predicts 30-day mortality after transcatheter aortic valve replacement: results from the Society of Thoracic Surgeons / American College of Cardiology Transcatheter Valve Therapy Registry. Circulation. 2016;133(14):1351-9.</mixed-citation>
      </ref>
      <ref id="B19">
        <label>19</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ramos</surname>
              <given-names>LR</given-names>
            </name>
            <name>
              <surname>Toniolo</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Cendoroglo</surname>
              <given-names>MS</given-names>
            </name>
            <name>
              <surname>Garcia</surname>
              <given-names>JT</given-names>
            </name>
            <name>
              <surname>Najas</surname>
              <given-names>MS</given-names>
            </name>
            <name>
              <surname>Perracini</surname>
              <given-names>M</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Two-year follow-up study of elderly residents in S. Paulo, Brazil: methodology and preliminary results</article-title>
          <source>Rev Sa&#250;de P&#250;blica</source>
          <year>1998</year>
          <volume>32</volume>
          <issue>5</issue>
          <fpage>397</fpage>
          <lpage>407</lpage>
        </element-citation>
        <mixed-citation>19. Ramos LR, Toniolo J, Cendoroglo MS, Garcia JT, Najas MS, Perracini M et al. Two-year follow-up study of elderly residents in S. Paulo, Brazil: methodology and preliminary results. Rev Sa&#250;de P&#250;blica. 1998;32(5):397-407.</mixed-citation>
      </ref>
      <ref id="B20">
        <label>20</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Smith</surname>
              <given-names>SM</given-names>
            </name>
            <name>
              <surname>Soubhi</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Fortin</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Hudon</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>O'Dowd</surname>
              <given-names>T</given-names>
            </name>
          </person-group>
          <article-title>Managing patients with multimorbidity: systematic review of interventions in primary care and community settings</article-title>
          <source>BMJ</source>
          <year>2012</year>
          <month>09</month>
          <day>03</day>
          <volume>345</volume>
          <elocation-id>e5205</elocation-id>
        </element-citation>
        <mixed-citation>20. Smith SM, Soubhi H, Fortin M, Hudon C, O'Dowd T. Managing patients with multimorbidity: systematic review of interventions in primary care and community settings. BMJ. 2012 Sep 3;345:e5205.</mixed-citation>
      </ref>
      <ref id="B21">
        <label>21</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Studenski</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Perera</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Patel</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Rosano</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Faulkner</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Inzitari</surname>
              <given-names>M</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Gait speed and survival in older adults</article-title>
          <source>JAMA</source>
          <year>2011</year>
          <volume>305</volume>
          <issue>1</issue>
          <fpage>50</fpage>
          <lpage>58</lpage>
        </element-citation>
        <mixed-citation>21. Studenski S, Perera S, Patel K, Rosano C, Faulkner K, Inzitari M et al. Gait speed and survival in older adults. JAMA. 2011;305(1):50-8.</mixed-citation>
      </ref>
      <ref id="B22">
        <label>22</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Freitas</surname>
              <given-names>EV</given-names>
            </name>
            <name>
              <surname>Costa</surname>
              <given-names>EF</given-names>
            </name>
            <name>
              <surname>Galera</surname>
              <given-names>CS</given-names>
            </name>
          </person-group>
          <chapter-title>Avalia&#231;&#227;o geri&#225;trica ampla</chapter-title>
          <person-group person-group-type="editor">
            <name>
              <surname>Freitas</surname>
              <given-names>EV</given-names>
            </name>
            <name>
              <surname>Py</surname>
              <given-names>L</given-names>
            </name>
          </person-group>
          <source>Tratado de geriatria e gerontologia</source>
          <edition>4. ed.</edition>
          <publisher-loc>Rio de Janeiro</publisher-loc>
          <publisher-name>Guanabara Koogan</publisher-name>
          <year>2016</year>
          <fpage>152</fpage>
          <lpage>166</lpage>
        </element-citation>
        <mixed-citation>22. Freitas EV, Costa EF, Galera CS. Avalia&#231;&#227;o geri&#225;trica ampla. In: In: Freitas EV, Py L. Tratado de geriatria e gerontologia. 4. ed. Rio de Janeiro: Guanabara Koogan; 2016. p. 152-66.</mixed-citation>
      </ref>
      <ref id="B23">
        <label>23</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Wajngarten</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
          <article-title>Geriatric cardiology: a subspecialty or a need?</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2006</year>
          <volume>87</volume>
          <issue>3</issue>
          <fpage>e8</fpage>
          <lpage>e9</lpage>
        </element-citation>
        <mixed-citation>23. Wajngarten M. Geriatric cardiology: a subspecialty or a need? Arq Bras Cardiol. 2006;87(3):e 8-9.</mixed-citation>
      </ref>
      <ref id="B24">
        <label>24</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Lucchetti</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Novaes</surname>
              <given-names>PH</given-names>
            </name>
            <name>
              <surname>Lucchetti</surname>
              <given-names>AL</given-names>
            </name>
          </person-group>
          <chapter-title>Polifarm&#225;cia e adequa&#231;&#227;o do uso de medicamentos</chapter-title>
          <person-group person-group-type="editor">
            <name>
              <surname>Freitas</surname>
              <given-names>EV</given-names>
            </name>
            <name>
              <surname>Py</surname>
              <given-names>L</given-names>
            </name>
          </person-group>
          <source>Tratado de geriatria e gerontologia</source>
          <edition>4. ed.</edition>
          <publisher-loc>Rio de Janeiro</publisher-loc>
          <publisher-name>Guanabara Koogan</publisher-name>
          <year>2016</year>
          <fpage>1024</fpage>
          <lpage>1030</lpage>
        </element-citation>
        <mixed-citation>24. Lucchetti G, Novaes PH, Lucchetti AL. Polifarm&#225;cia e adequa&#231;&#227;o do uso de medicamentos. In: Freitas EV, Py L. Tratado de geriatria e gerontologia. 4. ed. Rio de Janeiro: Guanabara Koogan; 2016. p. 1024-30.</mixed-citation>
      </ref>
      <ref id="B25">
        <label>25</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bavishi</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Bangalore</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Messerli</surname>
              <given-names>FH</given-names>
            </name>
          </person-group>
          <article-title>Outcomes of intensive blood pressure lowering in older hypertensive patients</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2017</year>
          <volume>69</volume>
          <issue>5</issue>
          <fpage>486</fpage>
          <lpage>493</lpage>
        </element-citation>
        <mixed-citation>25. Bavishi C, Bangalore S, Messerli FH. Outcomes of intensive blood pressure lowering in older hypertensive patients. J Am Coll Cardiol. 2017;69(5):486-93.</mixed-citation>
      </ref>
      <ref id="B26">
        <label>26</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bansilal</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Castellano</surname>
              <given-names>JM</given-names>
            </name>
            <name>
              <surname>Garrido</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Wei</surname>
              <given-names>HG</given-names>
            </name>
            <name>
              <surname>Freeman</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Spettell</surname>
              <given-names>C</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Assessing the impact of medication adherence on long-term cardiovascular outcomes</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2016</year>
          <volume>68</volume>
          <issue>8</issue>
          <fpage>789</fpage>
          <lpage>801</lpage>
        </element-citation>
        <mixed-citation>26. Bansilal S, Castellano JM, Garrido E, Wei HG, Freeman A, Spettell C et al. Assessing the impact of medication adherence on long-term cardiovascular outcomes. J Am Coll Cardiol. 2016;68(8):789-801.</mixed-citation>
      </ref>
      <ref id="B27">
        <label>27</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <collab>American Geriatrics Society 2015 Beers Criteria Update Expert Panel</collab>
          </person-group>
          <article-title>American Geriatrics Society 2015 updated Beers criteria for potentially inappropriate medication use in older adults</article-title>
          <source>J Am Geriatr Soc</source>
          <year>2015</year>
          <volume>63</volume>
          <issue>11</issue>
          <fpage>2227</fpage>
          <lpage>2246</lpage>
        </element-citation>
        <mixed-citation>27. American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 updated Beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11):2227-46.</mixed-citation>
      </ref>
      <ref id="B28">
        <label>28</label>
        <element-citation publication-type="webpage">
          <article-title>American Geriatrics Society 2015 Updated Beers Criteria for potentially inappropriate medication use in older adults</article-title>
          <date-in-citation content-type="access-date">2016 Sep 10</date-in-citation>
          <comment>Available from: <ext-link ext-link-type="uri" xlink:href="https://www.guidelinescentral.com/summaries/American-geriatrics-society-2015">https://www.guidelinescentral.com/summaries/American-geriatrics-society-2015</ext-link></comment>
        </element-citation>
        <mixed-citation>28. American Geriatrics Society 2015 Updated Beers Criteria for potentially inappropriate medication use in older adults. [Internet]. [Cited in 2016 Sep 10]. Available from: <ext-link ext-link-type="uri" xlink:href="https://www.guidelinescentral.com/summaries/American-geriatrics-society-2015">https://www.guidelinescentral.com/summaries/American-geriatrics-society-2015</ext-link>.</mixed-citation>
      </ref>
      <ref id="B29">
        <label>29</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Shehab</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Lovegrove</surname>
              <given-names>MC</given-names>
            </name>
            <name>
              <surname>Geller</surname>
              <given-names>AI</given-names>
            </name>
            <name>
              <surname>Rose</surname>
              <given-names>KO</given-names>
            </name>
            <name>
              <surname>Weidle</surname>
              <given-names>NJ</given-names>
            </name>
            <name>
              <surname>Budnitz</surname>
              <given-names>DS</given-names>
            </name>
          </person-group>
          <article-title>US Emergency Department Visits for Outpatient Adverse Drug Events, 2013-2014</article-title>
          <source>JAMA</source>
          <year>2016</year>
          <volume>316</volume>
          <issue>20</issue>
          <fpage>2115</fpage>
          <lpage>2125</lpage>
        </element-citation>
        <mixed-citation>29. Shehab N, Lovegrove MC, Geller AI, Rose KO, Weidle NJ, Budnitz DS. US Emergency Department Visits for Outpatient Adverse Drug Events, 2013-2014. JAMA. 2016;316(20):2115-25.</mixed-citation>
      </ref>
      <ref id="B30">
        <label>30</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Betz</surname>
              <given-names>JK</given-names>
            </name>
            <name>
              <surname>Katz</surname>
              <given-names>DF</given-names>
            </name>
            <name>
              <surname>Peterson</surname>
              <given-names>PN</given-names>
            </name>
            <name>
              <surname>Borne</surname>
              <given-names>RT</given-names>
            </name>
            <name>
              <surname>Al-Khatib</surname>
              <given-names>SM</given-names>
            </name>
            <name>
              <surname>Wang</surname>
              <given-names>Y</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Outcomes among older patients receiving implantable cardioverter-defibrillators for secondary prevention: from the NCDR ICD Registry</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2017</year>
          <volume>69</volume>
          <issue>3</issue>
          <fpage>265</fpage>
          <lpage>274</lpage>
        </element-citation>
        <mixed-citation>30. Betz JK, Katz DF, Peterson PN, Borne RT, Al-Khatib SM, Wang Y et al. Outcomes among older patients receiving implantable cardioverter-defibrillators for secondary prevention: from the NCDR ICD Registry. J Am Coll Cardiol. 2017;69(3):265-74.</mixed-citation>
      </ref>
      <ref id="B31">
        <label>31</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Kirkman</surname>
              <given-names>MS</given-names>
            </name>
            <name>
              <surname>Briscoe</surname>
              <given-names>VJ</given-names>
            </name>
            <name>
              <surname>Clark</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Florez</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Haas</surname>
              <given-names>LB</given-names>
            </name>
            <name>
              <surname>Halter</surname>
              <given-names>JB</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Diabetes in older adults</article-title>
          <source>Diabetes Care</source>
          <year>2012</year>
          <volume>35</volume>
          <issue>12</issue>
          <fpage>2650</fpage>
          <lpage>2664</lpage>
        </element-citation>
        <mixed-citation>31. Kirkman MS, Briscoe VJ, Clark N, Florez H, Haas LB, Halter JB et al. Diabetes in older adults. Diabetes Care. 2012;35(12):2650-64.</mixed-citation>
      </ref>
      <ref id="B32">
        <label>32</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <collab>American Diabetes Association</collab>
          </person-group>
          <article-title>11. Older adults</article-title>
          <source>Diabetes Care</source>
          <year>2017</year>
          <volume>40</volume>
          <supplement>Suppl 1</supplement>
          <fpage>S99</fpage>
          <lpage>S104</lpage>
        </element-citation>
        <mixed-citation>32. American Diabetes Association. 11. Older adults. Diabetes Care. 2017;40(Suppl 1):S99-104.</mixed-citation>
      </ref>
      <ref id="B33">
        <label>33</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Turner</surname>
              <given-names>RC</given-names>
            </name>
            <name>
              <surname>Holman</surname>
              <given-names>RR</given-names>
            </name>
            <name>
              <surname>Cull</surname>
              <given-names>CA</given-names>
            </name>
            <name>
              <surname>Stratton</surname>
              <given-names>IM</given-names>
            </name>
            <name>
              <surname>Matthews</surname>
              <given-names>DR</given-names>
            </name>
            <name>
              <surname>Frighi</surname>
              <given-names>V</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS33)</article-title>
          <source>Lancet</source>
          <year>1998</year>
          <volume>353</volume>
          <issue>9131</issue>
          <fpage>837</fpage>
          <lpage>853</lpage>
        </element-citation>
        <mixed-citation>33. Turner RC, Holman RR, Cull CA, Stratton IM, Matthews, DR, Frighi V et al.; UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS33). Lancet. 1998;353(9131):837-53.</mixed-citation>
      </ref>
      <ref id="B34">
        <label>34</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Holman</surname>
              <given-names>RR</given-names>
            </name>
            <name>
              <surname>Paul</surname>
              <given-names>SK</given-names>
            </name>
            <name>
              <surname>Bethel</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Matthews</surname>
              <given-names>DR</given-names>
            </name>
            <name>
              <surname>Neil</surname>
              <given-names>HA</given-names>
            </name>
          </person-group>
          <article-title>10-year follow-up of intensive glucose control in type 2 diabetes</article-title>
          <source>N Engl J Med</source>
          <year>2008</year>
          <volume>359</volume>
          <issue>15</issue>
          <fpage>1577</fpage>
          <lpage>1589</lpage>
        </element-citation>
        <mixed-citation>34. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359(15):1577-89.</mixed-citation>
      </ref>
      <ref id="B35">
        <label>35</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Gerstein</surname>
              <given-names>HC</given-names>
            </name>
            <name>
              <surname>Miller</surname>
              <given-names>ME</given-names>
            </name>
            <name>
              <surname>Byimgton</surname>
              <given-names>RP</given-names>
            </name>
            <name>
              <surname>Goff</surname>
              <given-names>DC</given-names>
              <suffix>Jr</suffix>
            </name>
            <name>
              <surname>Bigger</surname>
              <given-names>JT</given-names>
            </name>
            <name>
              <surname>Buse</surname>
              <given-names>JB</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Action to control cardiovascular risk in diabetes study group: effects of intensive glucose lowering in type 2 diabetes</article-title>
          <source>N Engl J Med</source>
          <year>2008</year>
          <volume>358</volume>
          <issue>24</issue>
          <fpage>2545</fpage>
          <lpage>2559</lpage>
        </element-citation>
        <mixed-citation>35. Gerstein HC, Miller ME, Byimgton RP, Goff DC Jr, Bigger JT, Buse JB et al.; Action to control cardiovascular risk in diabetes study group: effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545-59.</mixed-citation>
      </ref>
      <ref id="B36">
        <label>36</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Milleer</surname>
              <given-names>ME</given-names>
            </name>
            <name>
              <surname>Bonds</surname>
              <given-names>DE</given-names>
            </name>
            <name>
              <surname>Gerstein</surname>
              <given-names>HC</given-names>
            </name>
            <name>
              <surname>Seaquist</surname>
              <given-names>ER</given-names>
            </name>
            <name>
              <surname>Bergenstal</surname>
              <given-names>RM</given-names>
            </name>
            <name>
              <surname>Calles-Escandon</surname>
              <given-names>J</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>ACCORD Investigators. The effects of baseline characteristics, glycaemia treatment approach, and glycated haemoglobin concentration on the risk of severe hypoglycaemia: post hoc epidemiological analysis of the ACCORD study:</article-title>
          <source>BMJ</source>
          <year>2010</year>
          <month>01</month>
          <day>08</day>
          <volume>340</volume>
          <comment>b5444</comment>
        </element-citation>
        <mixed-citation>36. Milleer ME, Bonds DE, Gerstein HC, Seaquist ER, Bergenstal RM, Calles-Escandon J et al.; ACCORD Investigators. The effects of baseline characteristics, glycaemia treatment approach, and glycated haemoglobin concentration on the risk of severe hypoglycaemia: post hoc epidemiological analysis of the ACCORD study: BMJ. 2010 Jan 8;340:b5444.</mixed-citation>
      </ref>
      <ref id="B37">
        <label>37</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Patel</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Mac Mahon</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Chalmers</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Neal</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Billot</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Woodward</surname>
              <given-names>M</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes</article-title>
          <source>N Engl J Med</source>
          <year>2008</year>
          <volume>358</volume>
          <issue>24</issue>
          <fpage>2560</fpage>
          <lpage>2572</lpage>
        </element-citation>
        <mixed-citation>37. Patel A, Mac Mahon S, Chalmers J, Neal B, Billot L, Woodward M et al.; ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560-72.</mixed-citation>
      </ref>
      <ref id="B38">
        <label>38</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Duckworth</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>Abraira</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Moritz</surname>
              <given-names>TE</given-names>
            </name>
            <name>
              <surname>Reda</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Emanuele</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Reaven</surname>
              <given-names>PD</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes</article-title>
          <source>N Engl J Med</source>
          <year>2009</year>
          <volume>360</volume>
          <issue>2</issue>
          <fpage>129</fpage>
          <lpage>139</lpage>
          <comment>Erratum in: N Engl J Med. 2009;361(10):1028</comment>
        </element-citation>
        <mixed-citation>38. Duckworth W, Abraira C, Moritz TE, Reda D, Emanuele N, Reaven PD et al; VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360(2):129-39. Erratum in: N Engl J Med. 2009;361(10):1028.</mixed-citation>
      </ref>
      <ref id="B39">
        <label>39</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Currie</surname>
              <given-names>CJ</given-names>
            </name>
            <name>
              <surname>Peters</surname>
              <given-names>JR</given-names>
            </name>
            <name>
              <surname>Tynan</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Evans</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Heine</surname>
              <given-names>RJ</given-names>
            </name>
            <name>
              <surname>Bracco</surname>
              <given-names>OL</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Survival as a function of HbA(1c) in people with type 2 diabetes: a retrospective cohort study</article-title>
          <source>Lancet</source>
          <year>2010</year>
          <volume>375</volume>
          <issue>9713</issue>
          <fpage>481</fpage>
          <lpage>489</lpage>
        </element-citation>
        <mixed-citation>39. Currie CJ, Peters JR, Tynan A, Evans M, Heine RJ, Bracco OL et al. Survival as a function of HbA(1c) in people with type 2 diabetes: a retrospective cohort study. Lancet. 2010;375(9713):481-9.</mixed-citation>
      </ref>
      <ref id="B40">
        <label>40</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Huang</surname>
              <given-names>ES</given-names>
            </name>
            <name>
              <surname>Liu</surname>
              <given-names>JY</given-names>
            </name>
            <name>
              <surname>Moffer</surname>
              <given-names>HH</given-names>
            </name>
            <name>
              <surname>John</surname>
              <given-names>PM</given-names>
            </name>
            <name>
              <surname>Karter</surname>
              <given-names>AJ</given-names>
            </name>
          </person-group>
          <article-title>Glycemic control, complications, and death in older diabetic patients: the Diabetes and Aging Study</article-title>
          <source>Diabetes Care</source>
          <year>2011</year>
          <volume>34</volume>
          <issue>6</issue>
          <fpage>1329</fpage>
          <lpage>1336</lpage>
        </element-citation>
        <mixed-citation>40. Huang ES, Liu JY, Moffer HH, John PM, Karter AJ. Glycemic control, complications, and death in older diabetic patients: the Diabetes and Aging Study. Diabetes Care. 2011;34(6):1329-36.</mixed-citation>
      </ref>
      <ref id="B41">
        <label>41</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <collab>Sociedade Brasileira de Diabetes</collab>
          </person-group>
          <chapter-title>Atualiza&#231;&#227;o Brasileira sobre Diabetes</chapter-title>
          <source>S&#237;ndrome metab&#243;lica</source>
          <publisher-loc>Rio de Janeiro</publisher-loc>
          <publisher-name>Diagraphic</publisher-name>
          <year>2005</year>
        </element-citation>
        <mixed-citation>41. Sociedade Brasileira de Diabetes. Atualiza&#231;&#227;o Brasileira sobre Diabetes. S&#237;ndrome metab&#243;lica. Rio de Janeiro: Diagraphic; 2005.</mixed-citation>
      </ref>
      <ref id="B42">
        <label>42</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Little</surname>
              <given-names>D&#8217;A</given-names>
            </name>
          </person-group>
          <article-title>A review of smoking in the elderly</article-title>
          <source>Geriatrics &amp; Aging</source>
          <year>2002</year>
          <volume>5</volume>
          <issue>9</issue>
          <fpage>11</fpage>
          <lpage>14</lpage>
        </element-citation>
        <mixed-citation>42. Little D&#8217;A. A review of smoking in the elderly. Geriatrics &amp; Aging. 2002;5(9):11-4.</mixed-citation>
      </ref>
      <ref id="B43">
        <label>43</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Siegel</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Kuller</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Lazarus</surname>
              <given-names>NB</given-names>
            </name>
            <name>
              <surname>Black</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Feigal</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Hughes</surname>
              <given-names>G</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Predictors of cardiovascular events and mortality in the Systolic Hypertension in the Elderly Program Pilot Project</article-title>
          <source>Am J Epidemiol</source>
          <year>1987</year>
          <volume>126</volume>
          <issue>3</issue>
          <fpage>385</fpage>
          <lpage>399</lpage>
        </element-citation>
        <mixed-citation>43. Siegel D, Kuller L, Lazarus NB, Black D, Feigal D, Hughes G et al. Predictors of cardiovascular events and mortality in the Systolic Hypertension in the Elderly Program Pilot Project. Am J Epidemiol. 1987;126(3):385-99.</mixed-citation>
      </ref>
      <ref id="B44">
        <label>44</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Kawachi</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Colditz</surname>
              <given-names>GA</given-names>
            </name>
            <name>
              <surname>Speltzer</surname>
              <given-names>FE</given-names>
            </name>
            <name>
              <surname>Manson</surname>
              <given-names>JE</given-names>
            </name>
            <name>
              <surname>Stampfer</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Willett</surname>
              <given-names>WC</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>A prospective study of passive smoking and coronary artery disease</article-title>
          <source>Circulation</source>
          <year>1997</year>
          <volume>95</volume>
          <issue>10</issue>
          <fpage>2374</fpage>
          <lpage>2379</lpage>
        </element-citation>
        <mixed-citation>44. Kawachi I, Colditz GA, Speltzer FE, Manson JE, Stampfer MJ, Willett WC et al. A prospective study of passive smoking and coronary artery disease. Circulation. 1997;95(10):2374-9.</mixed-citation>
      </ref>
      <ref id="B45">
        <label>45</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Jajich</surname>
              <given-names>CL</given-names>
            </name>
            <name>
              <surname>Ostfeld</surname>
              <given-names>AM</given-names>
            </name>
            <name>
              <surname>Freeman</surname>
              <given-names>DH</given-names>
              <suffix>Jr</suffix>
            </name>
          </person-group>
          <article-title>Smoking and CHD: mortality in the elderly</article-title>
          <source>JAMA</source>
          <year>1984</year>
          <volume>252</volume>
          <issue>20</issue>
          <fpage>2831</fpage>
          <lpage>2834</lpage>
        </element-citation>
        <mixed-citation>45. Jajich CL, Ostfeld AM, Freeman DH Jr. Smoking and CHD: mortality in the elderly. JAMA. 1984;252(20):2831-4.</mixed-citation>
      </ref>
      <ref id="B46">
        <label>46</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <collab>World Health Organization (WHO)</collab>
          </person-group>
          <source>Tobacco knowledge summaries: tobacco and dementia</source>
          <publisher-loc>Geneva</publisher-loc>
          <year>2014</year>
        </element-citation>
        <mixed-citation>46. World Health Organization (WHO). Tobacco knowledge summaries: tobacco and dementia. Geneva; 2014.</mixed-citation>
      </ref>
      <ref id="B47">
        <label>47</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Dwyer</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Exposure to environmental tobacco smoke and coronary risk</article-title>
          <source>Circulation</source>
          <year>1997</year>
          <volume>96</volume>
          <issue>5</issue>
          <fpage>1367</fpage>
          <lpage>1369</lpage>
        </element-citation>
        <mixed-citation>47. Dwyer J. Exposure to environmental tobacco smoke and coronary risk. Circulation. 1997;96(5):1367-9.</mixed-citation>
      </ref>
      <ref id="B48">
        <label>48</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Hall</surname>
              <given-names>SM</given-names>
            </name>
            <name>
              <surname>Humfleet</surname>
              <given-names>GL</given-names>
            </name>
            <name>
              <surname>Gorecki</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Mu&#241;oz</surname>
              <given-names>RF</given-names>
            </name>
            <name>
              <surname>Reus</surname>
              <given-names>VI</given-names>
            </name>
            <name>
              <surname>Prochaska</surname>
              <given-names>JJ</given-names>
            </name>
          </person-group>
          <article-title>Older versus younger treatment-seeking smokers: differences in smoking behavior, drug and alcohol use, and psychosocial and physical functioning</article-title>
          <source>Nicotine Tob Res</source>
          <year>2008</year>
          <volume>10</volume>
          <issue>3</issue>
          <fpage>463</fpage>
          <lpage>470</lpage>
        </element-citation>
        <mixed-citation>48. Hall SM, Humfleet GL, Gorecki JA, Mu&#241;oz RF, Reus VI, Prochaska JJ. Older versus younger treatment-seeking smokers: differences in smoking behavior, drug and alcohol use, and psychosocial and physical functioning. Nicotine Tob Res. 2008;10(3):463-70.</mixed-citation>
      </ref>
      <ref id="B49">
        <label>49</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <collab>2008 PHS Guideline Update Panel, Liaisons, and Staff</collab>
          </person-group>
          <article-title>Treating tobacco use and dependence: 2008 Update U.S. Public Health Service Clinical Practice Guideline executive summary</article-title>
          <source>Respir Care</source>
          <year>2008</year>
          <volume>53</volume>
          <issue>9</issue>
          <fpage>1217</fpage>
          <lpage>1222</lpage>
        </element-citation>
        <mixed-citation>49. 2008 PHS Guideline Update Panel, Liaisons, and Staff. Treating tobacco use and dependence: 2008 Update U.S. Public Health Service Clinical Practice Guideline executive summary. Respir Care. 2008;53(9):1217-22.</mixed-citation>
      </ref>
      <ref id="B50">
        <label>50</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bratzler</surname>
              <given-names>DW</given-names>
            </name>
            <name>
              <surname>Oehlert</surname>
              <given-names>WH</given-names>
            </name>
            <name>
              <surname>Austelle</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
          <article-title>Smoking in the elderly &#8211; it&#180;s never too late to quit</article-title>
          <source>J Okla State Med Assoc</source>
          <year>2002</year>
          <volume>95</volume>
          <issue>3</issue>
          <fpage>185</fpage>
          <lpage>191</lpage>
        </element-citation>
        <mixed-citation>50. Bratzler DW, Oehlert WH, Austelle A. Smoking in the elderly &#8211; it&#180;s never too late to quit. J Okla State Med Assoc. 2002;95(3):185-91.</mixed-citation>
      </ref>
      <ref id="B51">
        <label>51</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Buckland</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Connolly</surname>
              <given-names>MJ</given-names>
            </name>
          </person-group>
          <article-title>Age-related differences in smoking cessation advice and support given to patients hospitalized with smoking-related illness</article-title>
          <source>Age Ageing</source>
          <year>2005</year>
          <volume>34</volume>
          <issue>6</issue>
          <fpage>639</fpage>
          <lpage>642</lpage>
        </element-citation>
        <mixed-citation>51. Buckland A, Connolly MJ. Age-related differences in smoking cessation advice and support given to patients hospitalized with smoking-related illness. Age Ageing. 2005;34(6):639-42.</mixed-citation>
      </ref>
      <ref id="B52">
        <label>52</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Andrews</surname>
              <given-names>JO</given-names>
            </name>
            <name>
              <surname>Heath</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Graham-Garcia</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Management of tobacco dependence in older adults: using evidence-based strategies</article-title>
          <source>J Gerontol Nurs</source>
          <year>2004</year>
          <volume>30</volume>
          <issue>12</issue>
          <fpage>13</fpage>
          <lpage>24</lpage>
        </element-citation>
        <mixed-citation>52. Andrews JO, Heath J, Graham-Garcia J. Management of tobacco dependence in older adults: using evidence-based strategies J Gerontol Nurs. 2004;30(12):13-24.</mixed-citation>
      </ref>
      <ref id="B53">
        <label>53</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Tait</surname>
              <given-names>RJ</given-names>
            </name>
            <name>
              <surname>Hulse</surname>
              <given-names>GK</given-names>
            </name>
            <name>
              <surname>Waterreus</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Flicker</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Lautenschlager</surname>
              <given-names>NT</given-names>
            </name>
            <name>
              <surname>Jamrozik</surname>
              <given-names>K</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Effectiveness of a smoking cessation intervention in older adults</article-title>
          <source>Addiction</source>
          <year>2007</year>
          <volume>102</volume>
          <issue>1</issue>
          <fpage>148</fpage>
          <lpage>155</lpage>
        </element-citation>
        <mixed-citation>53. Tait RJ, Hulse GK, Waterreus A, Flicker L, Lautenschlager NT, Jamrozik K et al. Effectiveness of a smoking cessation intervention in older adults. Addiction. 2007;102(1):148-55.</mixed-citation>
      </ref>
      <ref id="B54">
        <label>54</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Burton</surname>
              <given-names>LC</given-names>
            </name>
            <name>
              <surname>Paglia</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>German</surname>
              <given-names>PS</given-names>
            </name>
            <name>
              <surname>Shapiro</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Damiano</surname>
              <given-names>AM</given-names>
            </name>
          </person-group>
          <article-title>The effect among older persons of a general preventive visit on three health behaviors: smoking, excessive alcohol drinking, and sedentary lifestyle. The Medicare Preventive Services Research Team</article-title>
          <source>Prev Med</source>
          <year>1995</year>
          <volume>24</volume>
          <issue>5</issue>
          <fpage>492</fpage>
          <lpage>497</lpage>
        </element-citation>
        <mixed-citation>54. Burton LC, Paglia MJ, German PS, Shapiro S, Damiano AM. The effect among older persons of a general preventive visit on three health behaviors: smoking, excessive alcohol drinking, and sedentary lifestyle. The Medicare Preventive Services Research Team. Prev Med. 1995;24(5):492-7.</mixed-citation>
      </ref>
      <ref id="B55">
        <label>55</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Morgan</surname>
              <given-names>GD</given-names>
            </name>
            <name>
              <surname>Noll</surname>
              <given-names>EL</given-names>
            </name>
            <name>
              <surname>Orleans</surname>
              <given-names>CT</given-names>
            </name>
            <name>
              <surname>Rimer</surname>
              <given-names>BK</given-names>
            </name>
            <name>
              <surname>Amfoh</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Bonney</surname>
              <given-names>G</given-names>
            </name>
          </person-group>
          <article-title>Reaching midlife and older smokers: tailored interventions for routine medical care</article-title>
          <source>Prev Med</source>
          <year>1996</year>
          <volume>25</volume>
          <issue>3</issue>
          <fpage>346</fpage>
          <lpage>354</lpage>
        </element-citation>
        <mixed-citation>55. Morgan GD, Noll EL, Orleans CT, Rimer BK, Amfoh K, Bonney G. Reaching midlife and older smokers: tailored interventions for routine medical care. Prev Med. 1996;25(3):346-54.</mixed-citation>
      </ref>
      <ref id="B56">
        <label>56</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <collab>World Health Organization (WHO)</collab>
          </person-group>
          <source>The challenge of obesity in the WHO European region and the strategies for response</source>
          <publisher-loc>Denmark</publisher-loc>
          <publisher-name>World Health Organization</publisher-name>
          <year>2007</year>
          <fpage>1</fpage>
          <lpage>59</lpage>
        </element-citation>
        <mixed-citation>56. World Health Organization (WHO). The challenge of obesity in the WHO European region and the strategies for response. Denmark: World Health Organization; 2007. p. 1-59.</mixed-citation>
      </ref>
      <ref id="B57">
        <label>57</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Eiben</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Dey</surname>
              <given-names>DK</given-names>
            </name>
            <name>
              <surname>Rothenberg</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Steen</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Bj&#246;rkelund</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Bengtsson</surname>
              <given-names>C</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Obesity in 70-year-old Swedes: secular changes over 30 years</article-title>
          <source>Int J Obes (Lond)</source>
          <year>2005</year>
          <volume>29</volume>
          <issue>7</issue>
          <fpage>810</fpage>
          <lpage>817</lpage>
        </element-citation>
        <mixed-citation>57. Eiben G, Dey DK, Rothenberg E, Steen B, Bj&#246;rkelund C, Bengtsson C et al. Obesity in 70-year-old Swedes: secular changes over 30 years. Int J Obes (Lond). 2005,29(7):810-7.</mixed-citation>
      </ref>
      <ref id="B58">
        <label>58</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>McTigue</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Larson</surname>
              <given-names>JC</given-names>
            </name>
            <name>
              <surname>Valoski</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Burke</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Kotchen</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Lewis</surname>
              <given-names>CE</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Mortality and cardiac and vascular outcomes in extremely obese women</article-title>
          <source>JAMA</source>
          <year>2006</year>
          <volume>296</volume>
          <issue>1</issue>
          <fpage>79</fpage>
          <lpage>86</lpage>
        </element-citation>
        <mixed-citation>58. McTigue K, Larson JC, Valoski A, Burke G, Kotchen J, Lewis CE et al. Mortality and cardiac and vascular outcomes in extremely obese women. JAMA. 2006;296(1):79-86.</mixed-citation>
      </ref>
      <ref id="B59">
        <label>59</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Freedman</surname>
              <given-names>DM</given-names>
            </name>
            <name>
              <surname>Ron</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Ballard-Barbash</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Doody</surname>
              <given-names>MM</given-names>
            </name>
            <name>
              <surname>Linet</surname>
              <given-names>MS</given-names>
            </name>
          </person-group>
          <article-title>Body mass index and all-cause mortality in a nationwide US cohort</article-title>
          <source>Int J Obes (Lond)</source>
          <year>2006</year>
          <volume>30</volume>
          <issue>5</issue>
          <fpage>822</fpage>
          <lpage>829</lpage>
        </element-citation>
        <mixed-citation>59. Freedman DM, Ron E, Ballard-Barbash R, Doody MM, Linet MS. Body mass index and all-cause mortality in a nationwide US cohort. Int J Obes (Lond). 2006;30(5):822-9.</mixed-citation>
      </ref>
      <ref id="B60">
        <label>60</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Pischon</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Boeing</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Hoffmann</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Bergmann</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Schulze</surname>
              <given-names>MB</given-names>
            </name>
            <name>
              <surname>Overvad</surname>
              <given-names>K</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>General and abdominal adiposity and risk of death in Europe</article-title>
          <source>N Engl J Med</source>
          <year>2008</year>
          <volume>359</volume>
          <issue>20</issue>
          <fpage>2105</fpage>
          <lpage>2120</lpage>
          <comment>Erratum in: N Engl J Med. 2010;362(25):2433</comment>
        </element-citation>
        <mixed-citation>60. Pischon T, Boeing H, Hoffmann K, Bergmann M, Schulze MB, Overvad K et al. General and abdominal adiposity and risk of death in Europe. N Engl J Med. 2008;359(20):2105-20. Erratum in: N Engl J Med. 2010;362(25):2433.</mixed-citation>
      </ref>
      <ref id="B61">
        <label>61</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Janssen</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Katzmarzyk</surname>
              <given-names>PT</given-names>
            </name>
            <name>
              <surname>Ross</surname>
              <given-names>R</given-names>
            </name>
          </person-group>
          <article-title>Body mass index is inversely related to mortality in older people after adjustment for waist circumference</article-title>
          <source>J Am Geriatr Soc</source>
          <year>2005</year>
          <volume>53</volume>
          <issue>12</issue>
          <fpage>2112</fpage>
          <lpage>2118</lpage>
        </element-citation>
        <mixed-citation>61. Janssen I, Katzmarzyk PT, Ross R. Body mass index is inversely related to mortality in older people after adjustment for waist circumference. J Am Geriatr Soc. 2005;53(12):2112-8.</mixed-citation>
      </ref>
      <ref id="B62">
        <label>62</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Grabowski</surname>
              <given-names>DC</given-names>
            </name>
            <name>
              <surname>Ellis</surname>
              <given-names>JE</given-names>
            </name>
          </person-group>
          <article-title>High body mass index does not predict mortality in older people: analysis of the Longitudinal Study of Aging</article-title>
          <source>J Am Geriatr Soc</source>
          <year>2001</year>
          <volume>49</volume>
          <issue>7</issue>
          <fpage>968</fpage>
          <lpage>979</lpage>
        </element-citation>
        <mixed-citation>62. Grabowski DC, Ellis JE. High body mass index does not predict mortality in older people: analysis of the Longitudinal Study of Aging. J Am Geriatr Soc. 2001;49(7):968-79.</mixed-citation>
      </ref>
      <ref id="B63">
        <label>63</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Guallar-Castillon</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Balboa-Castillo</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Lopez-Garcia</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Le&#243;n-Mu&#241;oz</surname>
              <given-names>LM</given-names>
            </name>
            <name>
              <surname>Guti&#233;rrez-Fisac</surname>
              <given-names>JL</given-names>
            </name>
            <name>
              <surname>Banegas</surname>
              <given-names>JR</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>BMI, waist circumference, and mortality according to health status in the older adult population of Spain</article-title>
          <source>Obesity (Silver Spring)</source>
          <year>2009</year>
          <volume>17</volume>
          <issue>12</issue>
          <fpage>2232</fpage>
          <lpage>2238</lpage>
        </element-citation>
        <mixed-citation>63. Guallar-Castillon P, Balboa-Castillo T, Lopez-Garcia E, Le&#243;n-Mu&#241;oz LM, Guti&#233;rrez-Fisac JL, Banegas JR et al. BMI, waist circumference, and mortality according to health status in the older adult population of Spain. Obesity (Silver Spring). 2009;17(12):2232-38.</mixed-citation>
      </ref>
      <ref id="B64">
        <label>64</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Zamboni</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Mazzali</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Zoico</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Harris</surname>
              <given-names>TB</given-names>
            </name>
            <name>
              <surname>Meigs</surname>
              <given-names>JB</given-names>
            </name>
            <name>
              <surname>Di Francesco</surname>
              <given-names>V</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Health consequences of obesity in the elderly: a review of four unresolved questions</article-title>
          <source>Int J Obes (Lond)</source>
          <year>2005</year>
          <volume>29</volume>
          <issue>9</issue>
          <fpage>1011</fpage>
          <lpage>1029</lpage>
        </element-citation>
        <mixed-citation>64. Zamboni M, Mazzali G, Zoico E, Harris TB, Meigs JB, Di Francesco V et al. Health consequences of obesity in the elderly: a review of four unresolved questions. Int J Obes (Lond). 2005;29(9):1011-29.</mixed-citation>
      </ref>
      <ref id="B65">
        <label>65</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Flegal</surname>
              <given-names>KM</given-names>
            </name>
            <name>
              <surname>Kit</surname>
              <given-names>BK</given-names>
            </name>
            <name>
              <surname>Orpana</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Graubard</surname>
              <given-names>BI</given-names>
            </name>
          </person-group>
          <article-title>Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis</article-title>
          <source>JAMA</source>
          <year>2013</year>
          <volume>309</volume>
          <issue>1</issue>
          <fpage>71</fpage>
          <lpage>82</lpage>
        </element-citation>
        <mixed-citation>65. Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA. 2013;309(1):71-82.</mixed-citation>
      </ref>
      <ref id="B66">
        <label>66</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>McGee</surname>
              <given-names>DL</given-names>
            </name>
          </person-group>
          <article-title>Diverse Populations Collaboration. Body mass index and mortality: a meta-analysis based on person-level data from twenty-six observational studies</article-title>
          <source>Ann Epidemiol</source>
          <year>2005</year>
          <volume>15</volume>
          <issue>2</issue>
          <fpage>87</fpage>
          <lpage>97</lpage>
        </element-citation>
        <mixed-citation>66. McGee DL; Diverse Populations Collaboration. Body mass index and mortality: a meta-analysis based on person-level data from twenty-six observational studies. Ann Epidemiol. 2005;15(2):87-97.</mixed-citation>
      </ref>
      <ref id="B67">
        <label>67</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Janssen</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Mark</surname>
              <given-names>AE</given-names>
            </name>
          </person-group>
          <article-title>Elevated body mass index and mortality risk in the elderly</article-title>
          <source>Obes Rev</source>
          <year>2007</year>
          <volume>8</volume>
          <issue>1</issue>
          <fpage>41</fpage>
          <lpage>59</lpage>
        </element-citation>
        <mixed-citation>67. Janssen I, Mark AE. Elevated body mass index and mortality risk in the elderly. Obes Rev. 2007;8(1):41-59.</mixed-citation>
      </ref>
      <ref id="B68">
        <label>68</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <collab>World Health Organization (WHO)</collab>
          </person-group>
          <chapter-title>Consultation on obesity</chapter-title>
          <publisher-loc>Geneva</publisher-loc>
          <year>1999</year>
          <source>(WHO technical report series; 894)</source>
        </element-citation>
        <mixed-citation>68. World Health Organization (WHO). Consultation on obesity. Geneva; 1999. (WHO technical report series; 894).</mixed-citation>
      </ref>
      <ref id="B69">
        <label>69</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Mart&#237;nez-Gonz&#225;lez</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Garc&#237;a-Arellano</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Toledo</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Bes-Rastrollo</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Bull&#243;</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Corella</surname>
              <given-names>D</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Obesity indexes and total mortality among elderly subjects at high cardiovascular risk: The PREDIMED Study</article-title>
          <source>PLoS One</source>
          <year>2014</year>
          <volume>9</volume>
          <issue>7</issue>
          <elocation-id>e103246</elocation-id>
        </element-citation>
        <mixed-citation>69. Mart&#237;nez-Gonz&#225;lez MA, Garc&#237;a-Arellano A, Toledo E, Bes-Rastrollo M, Bull&#243; M, Corella D et al. Obesity indexes and total mortality among elderly subjects at high cardiovascular risk: The PREDIMED Study. PLoS One. 2014;9(7):e103246.</mixed-citation>
      </ref>
      <ref id="B70">
        <label>70</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>de Hollander</surname>
              <given-names>EL</given-names>
            </name>
            <name>
              <surname>Bemelmans</surname>
              <given-names>WJ</given-names>
            </name>
            <name>
              <surname>Boshuizen</surname>
              <given-names>HC</given-names>
            </name>
            <name>
              <surname>Friedrich</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Wallaschofski</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Guallar-Castill&#243;n</surname>
              <given-names>P</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>WC elderly collaborators. The association between waist circumference and risk of mortality considering body mass index in 65- to 74-year-olds: a meta-analysis of 29 cohorts involving more than 58 000 elderly persons</article-title>
          <source>Int J Epidemiol</source>
          <year>2012</year>
          <volume>41</volume>
          <issue>3</issue>
          <fpage>805</fpage>
          <lpage>817</lpage>
        </element-citation>
        <mixed-citation>70. de Hollander EL, Bemelmans WJ, Boshuizen HC, Friedrich N, Wallaschofski H, Guallar-Castill&#243;n P et al; WC elderly collaborators. The association between waist circumference and risk of mortality considering body mass index in 65- to 74-year-olds: a meta-analysis of 29 cohorts involving more than 58 000 elderly persons. Int J Epidemiol. 2012;41(3):805-17.</mixed-citation>
      </ref>
      <ref id="B71">
        <label>71</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Dhana</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Koolhaas</surname>
              <given-names>CM</given-names>
            </name>
            <name>
              <surname>van Rossum</surname>
              <given-names>EF</given-names>
            </name>
            <name>
              <surname>Ikram</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Hofman</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Kavousi</surname>
              <given-names>M</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Metabolically healthy obesity and the risk of cardiovascular disease in the elderly population</article-title>
          <source>PLoS One</source>
          <year>2016</year>
          <volume>11</volume>
          <issue>4</issue>
          <elocation-id>e0154273</elocation-id>
        </element-citation>
        <mixed-citation>71. Dhana K, Koolhaas CM, van Rossum EF, Ikram MA, Hofman A, Kavousi M et al. Metabolically healthy obesity and the risk of cardiovascular disease in the elderly population. PLoS One. 2016;11(4):e0154273.</mixed-citation>
      </ref>
      <ref id="B72">
        <label>72</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Thompson</surname>
              <given-names>PD</given-names>
            </name>
            <name>
              <surname>Arena</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Riebe</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Pescatello</surname>
              <given-names>LS</given-names>
            </name>
            <collab>American College of Sports Medicine</collab>
          </person-group>
          <article-title>ACSM new preparticipation health screening recommendations from ACSMs Guidelines for Exercise Testing and Prescription</article-title>
          <edition>Ninth</edition>
          <source>Curr Sports Med Rep</source>
          <year>2013</year>
          <volume>12</volume>
          <issue>4</issue>
          <fpage>215</fpage>
          <lpage>217</lpage>
        </element-citation>
        <mixed-citation>72. Thompson PD, Arena R, Riebe D, Pescatello LS; American College of Sports Medicine. ACSM new preparticipation health screening recommendations from ACSMs Guidelines for Exercise Testing and Prescription. Ninth edition. Curr Sports Med Rep. 2013;12(4):215-7.</mixed-citation>
      </ref>
      <ref id="B73">
        <label>73</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Whaley</surname>
              <given-names>MH</given-names>
            </name>
            <name>
              <surname>Brubaker</surname>
              <given-names>PH</given-names>
            </name>
            <name>
              <surname>Otto</surname>
              <given-names>RM</given-names>
            </name>
            <name>
              <surname>Armstrong</surname>
              <given-names>LE</given-names>
            </name>
          </person-group>
          <source>ACSM&#8217;S guidelines for exercise testing &amp; prescription</source>
          <publisher-loc>Philadelphia</publisher-loc>
          <publisher-name>Lippincott Williams &amp; Wilkins</publisher-name>
          <year>2006</year>
        </element-citation>
        <mixed-citation>73. Whaley MH, Brubaker PH, Otto RM, Armstrong LE. ACSM&#8217;S guidelines for exercise testing &amp; prescription. Philadelphia: Lippincott Williams &amp; Wilkins; 2006.</mixed-citation>
      </ref>
      <ref id="B74">
        <label>74</label>
        <element-citation publication-type="webpage">
          <person-group person-group-type="author">
            <collab>Canada Public Health Agency of Canada</collab>
          </person-group>
          <article-title>Physical activity tips for older adults (65 years and older)</article-title>
          <date-in-citation content-type="access-date">2017 Dec 10</date-in-citation>
          <comment>Available from: <ext-link ext-link-type="uri" xlink:href="https://www.canada/ca/content/dam/phac-aspx/migration/">https://www.canada/ca/content/dam/phac-aspx/migration/</ext-link></comment>
        </element-citation>
        <mixed-citation>74. Canada Public Health Agency of Canada. Physical activity tips for older adults (65 years and older). [Internet]. [Cited in 2017 Dec 10]. Available from: <ext-link ext-link-type="uri" xlink:href="https://www.canada/ca/content/dam/phac-aspx/migration/">https://www.canada/ca/content/dam/phac-aspx/migration/</ext-link></mixed-citation>
      </ref>
      <ref id="B75">
        <label>75</label>
        <element-citation publication-type="webpage">
          <person-group person-group-type="author">
            <collab>US Department of Health and Physical Activity Guidelines Advisory Committee.</collab>
          </person-group>
          <source>Report 2008</source>
          <date-in-citation content-type="access-date">2017 Dec 10</date-in-citation>
          <comment>Available from: <ext-link ext-link-type="uri" xlink:href="https://health.gov/paguidelines/report/pdf/committeeReport.pdf">https://health.gov/paguidelines/report/pdf/committeeReport.pdf</ext-link></comment>
        </element-citation>
        <mixed-citation>75. US Department of Health and Physical Activity Guidelines Advisory Committee. Report 2008. [Internet]. [Cited in 2017 Dec 10]. Available from: <ext-link ext-link-type="uri" xlink:href="https://health.gov/paguidelines/report/pdf/committeeReport.pdf">https://health.gov/paguidelines/report/pdf/committeeReport.pdf</ext-link>.</mixed-citation>
      </ref>
      <ref id="B76">
        <label>76</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Gravina</surname>
              <given-names>CF</given-names>
            </name>
            <name>
              <surname>Crespan</surname>
              <given-names>SM</given-names>
            </name>
            <name>
              <surname>Ara&#250;jo</surname>
              <given-names>N</given-names>
            </name>
          </person-group>
          <chapter-title>Envelhecimento e risco cardiovascular</chapter-title>
          <source>Sociedade de Cardiologia do Estado de S&#227;o Paulo (SOCESP)</source>
          <comment>Tratando de Cardiologia da Socesp</comment>
          <publisher-loc>S&#227;o Paulo</publisher-loc>
          <publisher-name>Manole</publisher-name>
          <year>2009</year>
        </element-citation>
        <mixed-citation>76. Gravina, CF, Crespan SM, Ara&#250;jo N. Envelhecimento e risco cardiovascular. In: Sociedade de Cardiologia do Estado de S&#227;o Paulo (SOCESP). Tratando de Cardiologia da Socesp. S&#227;o Paulo: Manole; 2009.</mixed-citation>
      </ref>
      <ref id="B77">
        <label>77</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Janssen</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Jolliffe</surname>
              <given-names>CJ</given-names>
            </name>
          </person-group>
          <article-title>Influence of physical activity on mortality in elderly with coronary artery disease</article-title>
          <source>Med Sci Sports Exerc</source>
          <year>2006</year>
          <volume>38</volume>
          <issue>3</issue>
          <fpage>418</fpage>
          <lpage>417</lpage>
        </element-citation>
        <mixed-citation>77. Janssen I, Jolliffe CJ. Influence of physical activity on mortality in elderly with coronary artery disease. Med Sci Sports Exerc. 2006;38(3):418-7.</mixed-citation>
      </ref>
      <ref id="B78">
        <label>78</label>
        <element-citation publication-type="webpage">
          <person-group person-group-type="author">
            <collab>World Health Organization (WHO)</collab>
          </person-group>
          <source>Physical activity and older adults</source>
          <date-in-citation content-type="access-date">2017 Feb 16</date-in-citation>
          <comment>Available from: <ext-link ext-link-type="uri" xlink:href="http://www.who.int/dietpshysicalactivity/factsheet-olderadults/en">http://www.who.int/dietpshysicalactivity/factsheet-olderadults/en</ext-link></comment>
        </element-citation>
        <mixed-citation>78. World Health Organization (WHO). Physical activity and older adults. [Cited in 2017 Feb 16]. Available from: <ext-link ext-link-type="uri" xlink:href="http://www.who.int/dietpshysicalactivity/factsheet-olderadults/en">http://www.who.int/dietpshysicalactivity/factsheet-olderadults/en</ext-link>.</mixed-citation>
      </ref>
      <ref id="B79">
        <label>79</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Meneghello</surname>
              <given-names>RS</given-names>
            </name>
            <name>
              <surname>Ara&#250;jo</surname>
              <given-names>CG</given-names>
            </name>
            <name>
              <surname>Stein</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Mastrocolla</surname>
              <given-names>LE</given-names>
            </name>
            <name>
              <surname>Albuquerque</surname>
              <given-names>PF</given-names>
            </name>
            <name>
              <surname>Serra</surname>
              <given-names>SM</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Sociedade Brasileira de Cardiologia. [III Guidelines of Sociedade Brasileira de Cardiologia on the exercise test]</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2010</year>
          <volume>95</volume>
          <supplement>5 Suppl 1</supplement>
          <fpage>1</fpage>
          <lpage>26</lpage>
        </element-citation>
        <mixed-citation>79. Meneghello RS, Ara&#250;jo CG, Stein R, Mastrocolla LE, Albuquerque PF, Serra SM et al; Sociedade Brasileira de Cardiologia. [III Guidelines of Sociedade Brasileira de Cardiologia on the exercise test]. Arq Bras Cardiol. 2010;95(5 Suppl 1):1-26.</mixed-citation>
      </ref>
      <ref id="B80">
        <label>80</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Freitas</surname>
              <given-names>EV</given-names>
            </name>
            <name>
              <surname>Py</surname>
              <given-names>L</given-names>
            </name>
          </person-group>
          <source>Tratado de geriatria e gerontologia</source>
          <edition>4. ed.</edition>
          <publisher-loc>Rio de Janeiro</publisher-loc>
          <publisher-name>Guanabara Koogan</publisher-name>
          <year>2016</year>
          <fpage>667</fpage>
          <lpage>674</lpage>
        </element-citation>
        <mixed-citation>80. Freitas EV, Py L. Tratado de geriatria e gerontologia. 4. ed. Rio de Janeiro: Guanabara Koogan; 2016. p. 667-74.</mixed-citation>
      </ref>
      <ref id="B81">
        <label>81</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Price</surname>
              <given-names>GM</given-names>
            </name>
            <name>
              <surname>Uauy</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Breeze</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Bulpitt</surname>
              <given-names>CJ</given-names>
            </name>
            <name>
              <surname>Fletcher</surname>
              <given-names>AE</given-names>
            </name>
          </person-group>
          <article-title>Weight, shape and mortality risk in older persons: elevated waist-hip ratio, not high body mass index, is associated with a greater risk of death</article-title>
          <source>Am J Clin Nutr</source>
          <year>2006</year>
          <volume>84</volume>
          <issue>2</issue>
          <fpage>449</fpage>
          <lpage>460</lpage>
        </element-citation>
        <mixed-citation>81. Price GM, Uauy R, Breeze E, Bulpitt CJ, Fletcher AE. Weight, shape and mortality risk in older persons: elevated waist-hip ratio, not high body mass index, is associated with a greater risk of death. Am J Clin Nutr. 2006;84(2):449-60.</mixed-citation>
      </ref>
      <ref id="B82">
        <label>82</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Costa</surname>
              <given-names>RC</given-names>
            </name>
            <name>
              <surname>Carrera</surname>
              <given-names>MA</given-names>
            </name>
          </person-group>
          <source>Ergometria, ergoespirometria, cintilografia e ecocardiografia de esfor&#231;o</source>
          <publisher-loc>S&#227;o Paulo</publisher-loc>
          <publisher-name>Atheneu</publisher-name>
          <year>2007</year>
          <fpage>59</fpage>
          <lpage>64</lpage>
        </element-citation>
        <mixed-citation>82. Costa RC, Carrera MA. Ergometria, ergoespirometria, cintilografia e ecocardiografia de esfor&#231;o. S&#227;o Paulo: Atheneu; 2007. p. 59-64.</mixed-citation>
      </ref>
      <ref id="B83">
        <label>83</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Moreira</surname>
              <given-names>MC</given-names>
            </name>
            <name>
              <surname>Montenegro</surname>
              <given-names>ST</given-names>
            </name>
            <name>
              <surname>Paola</surname>
              <given-names>AA</given-names>
            </name>
          </person-group>
          <source>Livro texto da Sociedade Brasileira de Cardiologia</source>
          <edition>2. ed.</edition>
          <publisher-loc>Barueri (SP)</publisher-loc>
          <publisher-name>Manole</publisher-name>
          <year>2015</year>
          <fpage>128</fpage>
          <lpage>165</lpage>
        </element-citation>
        <mixed-citation>83. Moreira MC, Montenegro ST, Paola AA. Livro texto da Sociedade Brasileira de Cardiologia. 2. ed. Barueri (SP): Manole; 2015. p.128.65.</mixed-citation>
      </ref>
      <ref id="B84">
        <label>84</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <collab>American College of Sports Medicine</collab>
          </person-group>
          <source>ACSM&#8217;s Guidelines for exercise testing &amp; prescription</source>
          <edition>7. ed.</edition>
          <publisher-loc>Baltimore</publisher-loc>
          <publisher-name>Lippincott Williams &amp; Wilkins</publisher-name>
          <year>2006</year>
        </element-citation>
        <mixed-citation>84. American College of Sports Medicine. ACSM&#8217;s Guidelines for exercise testing &amp; prescription. 7. ed. Baltimore: Lippincott Williams &amp; Wilkins; 2006.</mixed-citation>
      </ref>
      <ref id="B85">
        <label>85</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Katzel</surname>
              <given-names>LI</given-names>
            </name>
            <name>
              <surname>Blumenthal</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Sorkin</surname>
              <given-names>JD</given-names>
            </name>
            <name>
              <surname>Goldberg</surname>
              <given-names>AP</given-names>
            </name>
          </person-group>
          <chapter-title>Dyslipoproteinemia</chapter-title>
          <person-group person-group-type="editor">
            <name>
              <surname>Halter</surname>
              <given-names>JB</given-names>
            </name>
            <name>
              <surname>Ouslander</surname>
              <given-names>JG</given-names>
            </name>
            <name>
              <surname>Tinetti</surname>
              <given-names>ME</given-names>
            </name>
            <etal/>
          </person-group>
          <source>Hazzard&#8217;s geriatric medicine and gerontology</source>
          <edition>6</edition>
          <publisher-loc>New York</publisher-loc>
          <publisher-name>McGraw-Hill</publisher-name>
          <year>2009</year>
          <fpage>1325</fpage>
          <lpage>1342</lpage>
        </element-citation>
        <mixed-citation>85. Katzel LI, Blumenthal J, Sorkin JD, Goldberg AP. Dyslipoproteinemia. In: Halter JB, Ouslander JG, Tinetti ME et al. (editors). Hazzard&#8217;s geriatric medicine and gerontology. 6. ed. New York: McGraw-Hill; 2009. p. 1325-42.</mixed-citation>
      </ref>
      <ref id="B86">
        <label>86</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Long</surname>
              <given-names>SB</given-names>
            </name>
            <name>
              <surname>Blaha</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Blumenthal</surname>
              <given-names>RS</given-names>
            </name>
            <name>
              <surname>Michos</surname>
              <given-names>ED</given-names>
            </name>
          </person-group>
          <article-title>Clinical utility of rosuvastatin and other statins for cardiovascular risk reduction among the elderly</article-title>
          <source>Clin Interv Aging</source>
          <year>2011</year>
          <volume>6</volume>
          <fpage>27</fpage>
          <lpage>35</lpage>
        </element-citation>
        <mixed-citation>86. Long SB, Blaha MJ, Blumenthal RS, Michos ED. Clinical utility of rosuvastatin and other statins for cardiovascular risk reduction among the elderly. Clin Interv Aging. 2011;6:27-35.</mixed-citation>
      </ref>
      <ref id="B87">
        <label>87</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Shepherd</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Blauw</surname>
              <given-names>GJ</given-names>
            </name>
            <name>
              <surname>Murphy</surname>
              <given-names>MB</given-names>
            </name>
            <name>
              <surname>Bollen</surname>
              <given-names>EL</given-names>
            </name>
            <name>
              <surname>Buckley</surname>
              <given-names>BM</given-names>
            </name>
            <name>
              <surname>Cobbe</surname>
              <given-names>SM</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>PROSPER study group. PROspective Study of Pravastatin in the Elderly at Risk. Pravastatin in elderly individuals at risk of vascular disease (Prosper): a randomised controlled trial</article-title>
          <source>Lancet</source>
          <year>2002</year>
          <volume>360</volume>
          <issue>9346</issue>
          <fpage>1623</fpage>
          <lpage>1630</lpage>
        </element-citation>
        <mixed-citation>87. Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM et al. PROSPER study group. PROspective Study of Pravastatin in the Elderly at Risk. Pravastatin in elderly individuals at risk of vascular disease (Prosper): a randomised controlled trial. Lancet. 2002;360(9346):1623-30.</mixed-citation>
      </ref>
      <ref id="B88">
        <label>88</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Reiner</surname>
              <given-names>Z</given-names>
            </name>
            <name>
              <surname>Catapano</surname>
              <given-names>AL</given-names>
            </name>
            <name>
              <surname>De Backer</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Graham</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Taskinen</surname>
              <given-names>MR</given-names>
            </name>
            <name>
              <surname>Wiklund</surname>
              <given-names>O</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>European Association for Cardiovascular Prevention &amp; Rehabilitation, ESC Committee for Practice Guidelines (CPG) 2008-2010 and 2010-2012 Committees. ESC/EAS Guidelines for the management of dyslipidaemias: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS)</article-title>
          <source>Eur Heart J</source>
          <year>2011</year>
          <volume>32</volume>
          <issue>14</issue>
          <fpage>1769</fpage>
          <lpage>1818</lpage>
        </element-citation>
        <mixed-citation>88. Reiner Z, Catapano AL, De Backer G, Graham I, Taskinen MR, Wiklund O et al.; European Association for Cardiovascular Prevention &amp; Rehabilitation, ESC Committee for Practice Guidelines (CPG) 2008-2010 and 2010-2012 Committees. ESC/EAS Guidelines for the management of dyslipidaemias: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011;32(14):1769-818.</mixed-citation>
      </ref>
      <ref id="B89">
        <label>89</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Nasser</surname>
              <given-names>FJ</given-names>
            </name>
            <name>
              <surname>Almeida</surname>
              <given-names>MM</given-names>
            </name>
            <name>
              <surname>Silva</surname>
              <given-names>LS</given-names>
            </name>
            <name>
              <surname>Almeida</surname>
              <given-names>RG</given-names>
            </name>
            <name>
              <surname>Barbirato</surname>
              <given-names>GB</given-names>
            </name>
            <name>
              <surname>Mendlowicz</surname>
              <given-names>MV</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Psychiatric disorders and cardiovascular system: heart-brain interaction</article-title>
          <source>Int J Cardiovasc Sci</source>
          <year>2016</year>
          <volume>29</volume>
          <issue>1</issue>
          <fpage>65</fpage>
          <lpage>75</lpage>
        </element-citation>
        <mixed-citation>89. Nasser FJ, Almeida MM, Silva LS, Almeida RG, Barbirato GB, Mendlowicz MV et al. Psychiatric disorders and cardiovascular system: heart-brain interaction. Int J Cardiovasc Sci. 2016;29(1):65-75.</mixed-citation>
      </ref>
      <ref id="B90">
        <label>90</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Paj&#261;k</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Jankowski</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Kotseva</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Heidrich</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>de Smedt</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>de Bacquer</surname>
              <given-names>D</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>EUROASPIRE Study Group. Depression, anxiety, and risk factor control in patients after hospitalization for coronary heart disease: the EUROASPIRE III Study</article-title>
          <source>Eur J Prev Cardiol</source>
          <year>2013</year>
          <volume>20</volume>
          <issue>2</issue>
          <fpage>331</fpage>
          <lpage>340</lpage>
        </element-citation>
        <mixed-citation>90. Paj&#261;k A, Jankowski P, Kotseva K, Heidrich J, de Smedt D, De Bacquer D et al.; EUROASPIRE Study Group. Depression, anxiety, and risk factor control in patients after hospitalization for coronary heart disease: the EUROASPIRE III Study. Eur J Prev Cardiol. 2013;20(2):331-40.</mixed-citation>
      </ref>
      <ref id="B91">
        <label>91</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Whooley</surname>
              <given-names>MA</given-names>
            </name>
          </person-group>
          <article-title>To screen or not to screen? Depression in patients with cardiovascular disease</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2009</year>
          <volume>54</volume>
          <issue>10</issue>
          <fpage>891</fpage>
          <lpage>893</lpage>
        </element-citation>
        <mixed-citation>91. Whooley MA. To screen or not to screen? Depression in patients with cardiovascular disease. J Am Coll Cardiol. 2009;54(10):891-3.</mixed-citation>
      </ref>
      <ref id="B92">
        <label>92</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Gale</surname>
              <given-names>CR</given-names>
            </name>
            <name>
              <surname>Batty</surname>
              <given-names>GD</given-names>
            </name>
            <name>
              <surname>Osborn</surname>
              <given-names>DP</given-names>
            </name>
            <name>
              <surname>Tynelius</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Rasmussen</surname>
              <given-names>F</given-names>
            </name>
          </person-group>
          <article-title>Mental disorders across the adult life course and future coronary heart disease: evidence for general susceptibility</article-title>
          <source>Circulation</source>
          <year>2014</year>
          <volume>129</volume>
          <issue>2</issue>
          <fpage>186</fpage>
          <lpage>193</lpage>
          <comment>Erratum in: Circulation. 2015;131(20):e501</comment>
        </element-citation>
        <mixed-citation>92. Gale CR, Batty GD, Osborn DP, Tynelius P, Rasmussen F. Mental disorders across the adult life course and future coronary heart disease: evidence for general susceptibility. Circulation. 2014;129(2):186-93. Erratum in: Circulation. 2015;131(20):e501.</mixed-citation>
      </ref>
      <ref id="B93">
        <label>93</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Gustad</surname>
              <given-names>LT</given-names>
            </name>
            <name>
              <surname>Laugsand</surname>
              <given-names>LE</given-names>
            </name>
            <name>
              <surname>Janszky</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Dalen</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Bjerkeset</surname>
              <given-names>O</given-names>
            </name>
          </person-group>
          <article-title>Symptoms of anxiety and depression and risk of acute myocardial infarction: the HUNT 2 study</article-title>
          <source>Eur Heart J</source>
          <year>2014</year>
          <volume>35</volume>
          <issue>21</issue>
          <fpage>1394</fpage>
          <lpage>1403</lpage>
        </element-citation>
        <mixed-citation>93. Gustad LT, Laugsand LE, Janszky I, Dalen H, Bjerkeset O. Symptoms of anxiety and depression and risk of acute myocardial infarction: the HUNT 2 study. Eur Heart J. 2014;35(21):1394-403.</mixed-citation>
      </ref>
      <ref id="B94">
        <label>94</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Lichtman</surname>
              <given-names>JH</given-names>
            </name>
            <name>
              <surname>Froelicher</surname>
              <given-names>ES</given-names>
            </name>
            <name>
              <surname>Blumenthal</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Carney</surname>
              <given-names>RM</given-names>
            </name>
            <name>
              <surname>Doering</surname>
              <given-names>LV</given-names>
            </name>
            <name>
              <surname>Frasure-Smith</surname>
              <given-names>N</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>American Heart Association Statistics Committee of the Council on Epidemiology and Prevention and the Council on Cardiovascular and Stroke Nursing. Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: systematic review and recommendations: a scientific statement from the American Heart Association</article-title>
          <source>Circulation</source>
          <year>2014</year>
          <volume>129</volume>
          <issue>12</issue>
          <fpage>1350</fpage>
          <lpage>1369</lpage>
        </element-citation>
        <mixed-citation>94. Lichtman JH, Froelicher ES, Blumenthal JA, Carney RM, Doering LV, Frasure-Smith N et al.; American Heart Association Statistics Committee of the Council on Epidemiology and Prevention and the Council on Cardiovascular and Stroke Nursing. Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: systematic review and recommendations: a scientific statement from the American Heart Association. Circulation. 2014;129(12):1350-69.</mixed-citation>
      </ref>
      <ref id="B95">
        <label>95</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Messerli-B&#252;rgy</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Molloy</surname>
              <given-names>GJ</given-names>
            </name>
            <name>
              <surname>Poole</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Wikman</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Kaski</surname>
              <given-names>JC</given-names>
            </name>
            <name>
              <surname>Steptoe</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
          <article-title>Psychological coping and recurrent major adverse cardiac events following acute coronary syndrome</article-title>
          <source>Br J Psychiatry</source>
          <year>2015</year>
          <volume>207</volume>
          <issue>3</issue>
          <fpage>256</fpage>
          <lpage>261</lpage>
        </element-citation>
        <mixed-citation>95. Messerli-B&#252;rgy N, Molloy GJ, Poole L, Wikman A, Kaski JC, Steptoe A. Psychological coping and recurrent major adverse cardiac events following acute coronary syndrome. Br J Psychiatry. 2015;207(3):256-61.</mixed-citation>
      </ref>
      <ref id="B96">
        <label>96</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Yekehtaz</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Farokhnia</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Akhondzadeh</surname>
              <given-names>S</given-names>
            </name>
          </person-group>
          <article-title>Cardiovascular considerations in antidepressant therapy: an evidence-based review</article-title>
          <source>J Tehran Heart Cent</source>
          <year>2013</year>
          <volume>8</volume>
          <issue>4</issue>
          <fpage>169</fpage>
          <lpage>176</lpage>
        </element-citation>
        <mixed-citation>96. Yekehtaz H, Farokhnia M, Akhondzadeh S. Cardiovascular considerations in antidepressant therapy: an evidence-based review. J Tehran Heart Cent. 2013;8(4):169-76.</mixed-citation>
      </ref>
      <ref id="B97">
        <label>97</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Noordam</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Aarts</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Leening</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Tiemeier</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Franco</surname>
              <given-names>OH</given-names>
            </name>
            <name>
              <surname>Hofman</surname>
              <given-names>A</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Use of antidepressants and the risk of myocardial infarction in middle-aged and older adults: a matched case-control study</article-title>
          <source>Eur J Clin Pharmacol</source>
          <year>2016</year>
          <volume>72</volume>
          <issue>2</issue>
          <fpage>211</fpage>
          <lpage>218</lpage>
        </element-citation>
        <mixed-citation>97. Noordam R, Aarts N, Leening MJ, Tiemeier H, Franco OH, Hofman A et al. Use of antidepressants and the risk of myocardial infarction in middle-aged and older adults: a matched case-control study. Eur J Clin Pharmacol. 2016;72(2):211-8.</mixed-citation>
      </ref>
      <ref id="B98">
        <label>98</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Pizzi</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Rutjes</surname>
              <given-names>AW</given-names>
            </name>
            <name>
              <surname>Costa</surname>
              <given-names>GM</given-names>
            </name>
            <name>
              <surname>Fontana</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Mezzetti</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Manzoli</surname>
              <given-names>L</given-names>
            </name>
          </person-group>
          <article-title>Meta-analysis of selective serotonin reuptake inhibitors in patients with depression and coronary heart disease</article-title>
          <source>Am J Cardiol</source>
          <year>2011</year>
          <volume>107</volume>
          <issue>7</issue>
          <fpage>972</fpage>
          <lpage>979</lpage>
        </element-citation>
        <mixed-citation>98. Pizzi C, Rutjes AW, Costa GM, Fontana F, Mezzetti A, Manzoli L. Meta-analysis of selective serotonin reuptake inhibitors in patients with depression and coronary heart disease. Am J Cardiol. 2011;107(7):972-9.</mixed-citation>
      </ref>
      <ref id="B99">
        <label>99</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Hare</surname>
              <given-names>DL</given-names>
            </name>
            <name>
              <surname>Toukhsati</surname>
              <given-names>SR</given-names>
            </name>
            <name>
              <surname>Johansson</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Jaarsma</surname>
              <given-names>T</given-names>
            </name>
          </person-group>
          <article-title>Depression and cardiovascular disease: a clinical review</article-title>
          <source>Eur Heart J</source>
          <year>2014</year>
          <volume>35</volume>
          <issue>21</issue>
          <fpage>1365</fpage>
          <lpage>1372</lpage>
        </element-citation>
        <mixed-citation>99. Hare DL, Toukhsati SR, Johansson P, Jaarsma T. Depression and cardiovascular disease: a clinical review. Eur Heart J. 2014;35(21):1365-72.</mixed-citation>
      </ref>
      <ref id="B100">
        <label>100</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Chobanian</surname>
              <given-names>AV</given-names>
            </name>
            <name>
              <surname>Bakris</surname>
              <given-names>GL</given-names>
            </name>
            <name>
              <surname>Black</surname>
              <given-names>HR</given-names>
            </name>
            <name>
              <surname>Cushman</surname>
              <given-names>WC</given-names>
            </name>
            <name>
              <surname>Green</surname>
              <given-names>LA</given-names>
            </name>
            <name>
              <surname>Izzo</surname>
              <given-names>JL</given-names>
              <suffix>Jr</suffix>
            </name>
            <etal/>
          </person-group>
          <article-title>National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report</article-title>
          <source>JAMA</source>
          <year>2003</year>
          <volume>289</volume>
          <issue>19</issue>
          <fpage>2560</fpage>
          <lpage>2572</lpage>
          <comment>Erratum in: JAMA 2003;290(2):197</comment>
        </element-citation>
        <mixed-citation>100. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr et al.; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289(19):2560-72. Erratum in: JAMA 2003;290(2):197.</mixed-citation>
      </ref>
      <ref id="B101">
        <label>101</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Kim</surname>
              <given-names>SY</given-names>
            </name>
            <name>
              <surname>Guevara</surname>
              <given-names>JP</given-names>
            </name>
            <name>
              <surname>Kim</surname>
              <given-names>KM</given-names>
            </name>
            <name>
              <surname>Choi</surname>
              <given-names>HK</given-names>
            </name>
            <name>
              <surname>Heitjan</surname>
              <given-names>DF</given-names>
            </name>
            <name>
              <surname>Albert</surname>
              <given-names>DA</given-names>
            </name>
          </person-group>
          <article-title>Hyperuricemia and coronary heart disease: a systematic review and meta-analysis</article-title>
          <source>Arthritis Care Res (Hoboken)</source>
          <year>2010</year>
          <volume>62</volume>
          <issue>2</issue>
          <fpage>170</fpage>
          <lpage>180</lpage>
        </element-citation>
        <mixed-citation>101. Kim SY, Guevara JP, Kim KM, Choi HK, Heitjan DF, Albert DA. Hyperuricemia and coronary heart disease: a systematic review and meta-analysis. Arthritis Care Res (Hoboken). 2010;62(2):170-80.</mixed-citation>
      </ref>
      <ref id="B102">
        <label>102</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Gravina</surname>
              <given-names>CF</given-names>
            </name>
            <name>
              <surname>Franken</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Wenger</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Freitas</surname>
              <given-names>EV</given-names>
            </name>
            <name>
              <surname>Batlouni</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Rich</surname>
              <given-names>M</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Sociedade Brasileira de Cardiologia. [II Guidelines of Brazilian Society of Cardiology in geriatric cardiology]</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2010</year>
          <volume>95</volume>
          <supplement>3 Suppl 2</supplement>
          <fpage>e16</fpage>
          <lpage>e76</lpage>
        </element-citation>
        <mixed-citation>102. Gravina CF, Franken R, Wenger N, Freitas EV, Batlouni M, Rich M et al.; Sociedade Brasileira de Cardiologia. [II Guidelines of Brazilian Society of Cardiology in geriatric cardiology]. Arq Bras Cardiol. 2010;95(3 Suppl 2):e16-76.</mixed-citation>
      </ref>
      <ref id="B103">
        <label>103</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Shepherd</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Blauw</surname>
              <given-names>GJ</given-names>
            </name>
            <name>
              <surname>Murphy</surname>
              <given-names>MB</given-names>
            </name>
            <name>
              <surname>Bollen</surname>
              <given-names>EL</given-names>
            </name>
            <name>
              <surname>Buckley</surname>
              <given-names>BM</given-names>
            </name>
            <name>
              <surname>Cobbe</surname>
              <given-names>SM</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>PROSPER study group. PROspective Study of Pravastatin in the Elderly at Risk. Pravastatin in elderly individuals at risk of vascular disease (Prosper): a randomised controlled trial</article-title>
          <source>Lancet</source>
          <year>2002</year>
          <volume>360</volume>
          <issue>9346</issue>
          <fpage>1623</fpage>
          <lpage>1630</lpage>
        </element-citation>
        <mixed-citation>103. Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM et al. PROSPER study group. PROspective Study of Pravastatin in the Elderly at Risk. Pravastatin in elderly individuals at risk of vascular disease (Prosper): a randomised controlled trial. Lancet. 2002;360(9346):1623-30.</mixed-citation>
      </ref>
      <ref id="B104">
        <label>104</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Monteiro</surname>
              <given-names>FC</given-names>
              <suffix>J&#250;nior</suffix>
            </name>
            <name>
              <surname>Mandarino</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Salgado</surname>
              <given-names>JV</given-names>
            </name>
            <name>
              <surname>Lages</surname>
              <given-names>JS</given-names>
            </name>
            <name>
              <surname>Salgado</surname>
              <given-names>N</given-names>
              <suffix>Filho</suffix>
            </name>
          </person-group>
          <article-title>Vitamin D deficiency: a new cardiovascular risk fator?</article-title>
          <source>Rev Bras Cardiol</source>
          <year>2014</year>
          <volume>27</volume>
          <issue>5</issue>
          <fpage>356</fpage>
          <lpage>365</lpage>
        </element-citation>
        <mixed-citation>104. Monteiro J&#250;nior FC, Mandarino N, Salgado JV, Lages JS, Salgado Filho N. Vitamin D deficiency: a new cardiovascular risk fator? Rev Bras Cardiol. 2014;27(5):356-65.</mixed-citation>
      </ref>
      <ref id="B105">
        <label>105</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Martins</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Wolf</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Pan</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Zadshir</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Tareen</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Thadhani</surname>
              <given-names>R</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey</article-title>
          <source>Arch Intern Med</source>
          <year>2007</year>
          <volume>167</volume>
          <issue>11</issue>
          <fpage>1159</fpage>
          <lpage>1165</lpage>
        </element-citation>
        <mixed-citation>105. Martins D, Wolf M, Pan D, Zadshir A, Tareen N, Thadhani R et al. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2007;167(11):1159-65.</mixed-citation>
      </ref>
      <ref id="B106">
        <label>106</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Anderson</surname>
              <given-names>TJ</given-names>
            </name>
            <name>
              <surname>Gr&#233;goire</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Hegele</surname>
              <given-names>RA</given-names>
            </name>
            <name>
              <surname>Couture</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Mancini</surname>
              <given-names>GB</given-names>
            </name>
            <name>
              <surname>McPherson</surname>
              <given-names>R</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult</article-title>
          <source>Can J Cardiol</source>
          <year>2013</year>
          <volume>29</volume>
          <issue>2</issue>
          <fpage>151</fpage>
          <lpage>167</lpage>
        </element-citation>
        <mixed-citation>106. Anderson TJ, Gr&#233;goire J, Hegele RA, Couture P, Mancini GB, McPherson R et al. 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2013;29(2):151-67.</mixed-citation>
      </ref>
      <ref id="B107">
        <label>107</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Wang</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Song</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Manson</surname>
              <given-names>JE</given-names>
            </name>
            <name>
              <surname>Pilz</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>M&#228;rz</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>Micha&#235;lsson</surname>
              <given-names>K</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease</article-title>
          <source>Circ Cardiovasc Qual Outcomes</source>
          <year>2012</year>
          <volume>5</volume>
          <issue>6</issue>
          <fpage>819</fpage>
          <lpage>829</lpage>
        </element-citation>
        <mixed-citation>107. Wang L, Song Y, Manson JE, Pilz S, M&#228;rz W, Micha&#235;lsson K et al. Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease. Circ Cardiovasc Qual Outcomes. 2012;5(6):819-29.</mixed-citation>
      </ref>
      <ref id="B108">
        <label>108</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bautista-Ni&#241;o</surname>
              <given-names>PK</given-names>
            </name>
            <name>
              <surname>Portilla-Fernandez</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Vaughan</surname>
              <given-names>DE</given-names>
            </name>
            <name>
              <surname>Danser</surname>
              <given-names>AH</given-names>
            </name>
            <name>
              <surname>Roks</surname>
              <given-names>AJ</given-names>
            </name>
          </person-group>
          <article-title>DNA damage: a main determinant of vascular aging</article-title>
          <source>Int J Mol Sci</source>
          <year>2016</year>
          <volume>17</volume>
          <issue>5</issue>
          <fpage>E748</fpage>
          <lpage>E748</lpage>
        </element-citation>
        <mixed-citation>108. Bautista-Ni&#241;o PK, Portilla-Fernandez E, Vaughan DE, Danser AH, Roks AJ. DNA damage: a main determinant of vascular aging. Int J Mol Sci. 2016;17(5). pii: E748.</mixed-citation>
      </ref>
      <ref id="B109">
        <label>109</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Kuller</surname>
              <given-names>LH</given-names>
            </name>
            <name>
              <surname>Arnold</surname>
              <given-names>AM</given-names>
            </name>
            <name>
              <surname>Psaty</surname>
              <given-names>BM</given-names>
            </name>
            <name>
              <surname>Robbins</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>O'Leary</surname>
              <given-names>DH</given-names>
            </name>
            <name>
              <surname>Tracy</surname>
              <given-names>RP</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>10-year follow-up of subclinical cardiovascular disease and risk of coronary heart disease in the Cardiovascular Health Study</article-title>
          <source>Arch Intern Med</source>
          <year>2006</year>
          <volume>166</volume>
          <issue>1</issue>
          <fpage>71</fpage>
          <lpage>78</lpage>
        </element-citation>
        <mixed-citation>109. Kuller LH, Arnold AM, Psaty BM, Robbins JA, O'Leary DH, Tracy RP et al. 10-year follow-up of subclinical cardiovascular disease and risk of coronary heart disease in the Cardiovascular Health Study. Arch Intern Med. 2006;166(1):71-8.</mixed-citation>
      </ref>
      <ref id="B110">
        <label>110</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Mozaffarian</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Furberg</surname>
              <given-names>CD</given-names>
            </name>
            <name>
              <surname>Psaty</surname>
              <given-names>BM</given-names>
            </name>
            <name>
              <surname>Siscovick</surname>
              <given-names>D</given-names>
            </name>
          </person-group>
          <article-title>Physical activity and incidence of atrial fibrillation in older adults: the cardiovascular health study</article-title>
          <source>Circulation</source>
          <year>2008</year>
          <volume>118</volume>
          <issue>8</issue>
          <fpage>800</fpage>
          <lpage>807</lpage>
        </element-citation>
        <mixed-citation>110. Mozaffarian D, Furberg CD, Psaty BM, Siscovick D. Physical activity and incidence of atrial fibrillation in older adults: the cardiovascular health study. Circulation. 2008;118(8):800-7.</mixed-citation>
      </ref>
      <ref id="B111">
        <label>111</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Wang</surname>
              <given-names>TJ</given-names>
            </name>
            <name>
              <surname>Gona</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Larson</surname>
              <given-names>MG</given-names>
            </name>
            <name>
              <surname>Tofler</surname>
              <given-names>GH</given-names>
            </name>
            <name>
              <surname>Levy</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Newton-Cheh</surname>
              <given-names>C</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Multiple biomarkers for the prediction of first major cardiovascular events and death</article-title>
          <source>N Engl J Med</source>
          <year>2006</year>
          <volume>355</volume>
          <issue>25</issue>
          <fpage>2631</fpage>
          <lpage>2639</lpage>
        </element-citation>
        <mixed-citation>111. Wang TJ, Gona P, Larson MG, Tofler GH, Levy D, Newton-Cheh C et al. Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med. 2006;355(25):2631-9.</mixed-citation>
      </ref>
      <ref id="B112">
        <label>112</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Rich</surname>
              <given-names>MW</given-names>
            </name>
            <name>
              <surname>Chyun</surname>
              <given-names>DA</given-names>
            </name>
            <name>
              <surname>Skolnick</surname>
              <given-names>AH</given-names>
            </name>
            <name>
              <surname>Alexander</surname>
              <given-names>KP</given-names>
            </name>
            <name>
              <surname>Forman</surname>
              <given-names>DE</given-names>
            </name>
            <name>
              <surname>Kitzman</surname>
              <given-names>DW</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Knowledge gaps in cardiovascular care of older adults: a scientific statement from the American Heart Association, American College of Cardiology, and American Geriatrics Society: executive summary</article-title>
          <source>J Am Geriatr Soc</source>
          <year>2016</year>
          <volume>64</volume>
          <issue>11</issue>
          <fpage>2185</fpage>
          <lpage>2192</lpage>
        </element-citation>
        <mixed-citation>112. Rich MW, Chyun DA, Skolnick AH, Alexander KP, Forman DE, Kitzman DW et al. Knowledge gaps in cardiovascular care of older adults: a scientific statement from the American Heart Association, American College of Cardiology, and American Geriatrics Society: executive summary. J Am Geriatr Soc. 2016;64(11):2185-92.</mixed-citation>
      </ref>
      <ref id="B113">
        <label>113</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Erbel</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Aboyans</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Boileau</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Bossone</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Bartolomeo</surname>
              <given-names>RD</given-names>
            </name>
            <name>
              <surname>Eggebrecht</surname>
              <given-names>H</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>ESC Committee for Practice Guidelines. 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases. Document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC)</article-title>
          <source>Eur Heart J</source>
          <year>2014</year>
          <volume>35</volume>
          <issue>41</issue>
          <fpage>2873</fpage>
          <lpage>2926</lpage>
        </element-citation>
        <mixed-citation>113. Erbel R, Aboyans V, Boileau C, Bossone E, Bartolomeo RD, Eggebrecht H et al.; ESC Committee for Practice Guidelines. 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases. Document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC). Eur Heart J. 2014;35(41):2873-926.</mixed-citation>
      </ref>
      <ref id="B114">
        <label>114</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Boodhwani</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Andelfinger</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Leipsic</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Lindsay</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>McMurtry</surname>
              <given-names>MS</given-names>
            </name>
            <name>
              <surname>Therrien</surname>
              <given-names>J</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Canadian Cardiovascular Society. Canadian Cardiovascular Society position statement on the management of thoracic aortic disease</article-title>
          <source>Can J Cardiol</source>
          <year>2014</year>
          <volume>30</volume>
          <issue>6</issue>
          <fpage>577</fpage>
          <lpage>589</lpage>
        </element-citation>
        <mixed-citation>114. Boodhwani M, Andelfinger G, Leipsic J, Lindsay T, McMurtry MS, Therrien J et al.; Canadian Cardiovascular Society. Canadian Cardiovascular Society position statement on the management of thoracic aortic disease. Can J Cardiol. 2014;30(6):577-89.</mixed-citation>
      </ref>
      <ref id="B115">
        <label>115</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Rooke</surname>
              <given-names>TW</given-names>
            </name>
            <name>
              <surname>Hirsch</surname>
              <given-names>AT</given-names>
            </name>
            <name>
              <surname>Misra</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Sidawy</surname>
              <given-names>AN</given-names>
            </name>
            <name>
              <surname>Beckman</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Findeiss</surname>
              <given-names>L</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>American College of Cardiology Foundation Task Force; American Heart Association Task Force. Management of patients with peripheral artery disease (Compilation of 2005 and 2011 ACCF/AHA Guideline Recommendations). A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2013</year>
          <volume>61</volume>
          <issue>14</issue>
          <fpage>1555</fpage>
          <lpage>1570</lpage>
        </element-citation>
        <mixed-citation>115. Rooke TW, Hirsch AT, Misra S, Sidawy AN, Beckman JA, Findeiss L et al.; American College of Cardiology Foundation Task Force; American Heart Association Task Force. Management of patients with peripheral artery disease (Compilation of 2005 and 2011 ACCF/AHA Guideline Recommendations). A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;61(14):1555-70.</mixed-citation>
      </ref>
      <ref id="B116">
        <label>116</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Hiratzka</surname>
              <given-names>LF</given-names>
            </name>
            <name>
              <surname>Bakris</surname>
              <given-names>GL</given-names>
            </name>
            <name>
              <surname>Beckman</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Bersin</surname>
              <given-names>RM</given-names>
            </name>
            <name>
              <surname>Carr</surname>
              <given-names>VF</given-names>
            </name>
            <name>
              <surname>Casey</surname>
              <given-names>DE</given-names>
              <suffix>Jr</suffix>
            </name>
            <etal/>
          </person-group>
          <article-title>American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines; American Association for Thoracic Surgery; American College of Radiology; American Stroke Association; Society of Cardiovascular Anesthesiologists; Society for Cardiovascular Angiography and Interventions; Society of Interventional Radiology; Society of Thoracic Surgeons; Society for Vascular Medicine. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the diagnosis and management of patients with thoracic aortic disease. A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2010</year>
          <volume>55</volume>
          <issue>14</issue>
          <fpage>e27</fpage>
          <lpage>e129</lpage>
          <comment>Erratum in: J Am Coll Cardiol. 2013; 62 (11):1039-40</comment>
        </element-citation>
        <mixed-citation>116. Hiratzka LF, Bakris GL, Beckman JA, Bersin RM, Carr VF, Casey DE Jr et al.; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines; American Association for Thoracic Surgery; American College of Radiology; American Stroke Association; Society of Cardiovascular Anesthesiologists; Society for Cardiovascular Angiography and Interventions; Society of Interventional Radiology; Society of Thoracic Surgeons; Society for Vascular Medicine. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the diagnosis and management of patients with thoracic aortic disease. A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. J Am Coll Cardiol. 2010;55(14):e27-129. Erratum in: J Am Coll Cardiol. 2013;62(11):1039-40.</mixed-citation>
      </ref>
      <ref id="B117">
        <label>117</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Brott</surname>
              <given-names>TG</given-names>
            </name>
            <name>
              <surname>Hobson</surname>
              <given-names>RW 2nd</given-names>
            </name>
            <name>
              <surname>Howard</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Roubin</surname>
              <given-names>GS</given-names>
            </name>
            <name>
              <surname>Clark</surname>
              <given-names>WM</given-names>
            </name>
            <name>
              <surname>Brooks</surname>
              <given-names>W</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>CREST Investigators. Stenting versus endarterectomy for treatment of carotid-artery stenosis</article-title>
          <source>N Engl J Med</source>
          <year>2010</year>
          <volume>363</volume>
          <issue>1</issue>
          <fpage>11</fpage>
          <lpage>23</lpage>
          <comment>Erratum in: N Engl J Med. 2010;363(2):198. N Engl J Med. 2010;363(5):498</comment>
        </element-citation>
        <mixed-citation>117. Brott TG, Hobson RW 2nd, Howard G, Roubin GS, Clark WM, Brooks W et al.; CREST Investigators. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med. 2010;363(1):11-23. Erratum in: N Engl J Med. 2010;363(2):198. N Engl J Med. 2010;363(5):498.</mixed-citation>
      </ref>
      <ref id="B118">
        <label>118</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Brott</surname>
              <given-names>TG</given-names>
            </name>
            <name>
              <surname>Howard</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Roubin</surname>
              <given-names>GS</given-names>
            </name>
            <name>
              <surname>Meschia</surname>
              <given-names>JF</given-names>
            </name>
            <name>
              <surname>Mackey</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Brooks</surname>
              <given-names>W</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>CREST Investigators. Long-term results of stenting versus endarterectomy for carotid-artery stenosis</article-title>
          <source>N Engl J Med</source>
          <year>2016</year>
          <volume>374</volume>
          <issue>11</issue>
          <fpage>1021</fpage>
          <lpage>1031</lpage>
        </element-citation>
        <mixed-citation>118. Brott TG, Howard G, Roubin GS, Meschia JF, Mackey A, Brooks W et al.; CREST Investigators. Long-term results of stenting versus endarterectomy for carotid-artery stenosis. N Engl J Med. 2016;374(11):1021-31.</mixed-citation>
      </ref>
      <ref id="B119">
        <label>119</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Rosenfield</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Matsumura</surname>
              <given-names>JS</given-names>
            </name>
            <name>
              <surname>Chaturvedi</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Riles</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Ansel</surname>
              <given-names>GM</given-names>
            </name>
            <name>
              <surname>Metzger</surname>
              <given-names>DC</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>ACT I Investigators. Randomized trial of stent versus surgery for asymptomatic carotid stenosis</article-title>
          <source>N Engl J Med</source>
          <year>2016</year>
          <volume>374</volume>
          <issue>11</issue>
          <fpage>1011</fpage>
          <lpage>1020</lpage>
        </element-citation>
        <mixed-citation>119. Rosenfield K, Matsumura JS, Chaturvedi S, Riles T, Ansel GM, Metzger DC et al.; ACT I Investigators. Randomized trial of stent versus surgery for asymptomatic carotid stenosis. N Engl J Med. 2016;374(11):1011-20.</mixed-citation>
      </ref>
      <ref id="B120">
        <label>120</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Spence</surname>
              <given-names>JD</given-names>
            </name>
            <name>
              <surname>Naylor</surname>
              <given-names>AR</given-names>
            </name>
          </person-group>
          <article-title>Endarterectomy, stenting, or neither for asymptomatic carotid-artery stenosis</article-title>
          <source>N Engl J Med</source>
          <year>2016</year>
          <volume>374</volume>
          <issue>11</issue>
          <fpage>1087</fpage>
          <lpage>1088</lpage>
        </element-citation>
        <mixed-citation>120. Spence JD, Naylor AR. Endarterectomy, stenting, or neither for asymptomatic carotid-artery stenosis. N Engl J Med. 2016;374(11):1087-8.</mixed-citation>
      </ref>
      <ref id="B121">
        <label>121</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Naylor</surname>
              <given-names>AR</given-names>
            </name>
          </person-group>
          <article-title>Why is the management of asymptomatic carotid disease so controversial?</article-title>
          <source>Surgeon</source>
          <year>2015</year>
          <volume>13</volume>
          <issue>1</issue>
          <fpage>34</fpage>
          <lpage>43</lpage>
        </element-citation>
        <mixed-citation>121. Naylor AR. Why is the management of asymptomatic carotid disease so controversial? Surgeon. 2015;13(1):34-43.</mixed-citation>
      </ref>
      <ref id="B122">
        <label>122</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Brott</surname>
              <given-names>TG</given-names>
            </name>
            <name>
              <surname>Halperin</surname>
              <given-names>JL</given-names>
            </name>
            <name>
              <surname>Abbara</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Bacharach</surname>
              <given-names>JM</given-names>
            </name>
            <name>
              <surname>Barr</surname>
              <given-names>JD</given-names>
            </name>
            <name>
              <surname>Bush</surname>
              <given-names>RL</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>2011ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS Guideline on the management of patients with extracranial carotid and vertebral artery disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American Stroke Association, American Association of Neuroscience Nurses, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Congress of Neurological Surgeons, Society of Atherosclerosis Imaging and Prevention, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, Society for Vascular Medicine, and Society for Vascular Surgery</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2011</year>
          <volume>57</volume>
          <issue>8</issue>
          <fpage>e16</fpage>
          <lpage>e94</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jacc.2010.11.006</pub-id>
          <comment>Erratum in: J Am Coll Cardiol. 2012;60(6):566. J Am Coll Cardiol. 2011;57(23):2379</comment>
        </element-citation>
        <mixed-citation>122. Brott TG, Halperin JL, Abbara S, Bacharach JM, Barr JD, Bush RL et al. 2011ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS Guideline on the management of patients with extracranial carotid and vertebral artery disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American Stroke Association, American Association of Neuroscience Nurses, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Congress of Neurological Surgeons, Society of Atherosclerosis Imaging and Prevention, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, Society for Vascular Medicine, and Society for Vascular Surgery. J Am Coll Cardiol. 2011;57(8):e16-94. doi: 10.1016/j.jacc.2010.11.006. Erratum in: J Am Coll Cardiol. 2012;60(6):566. J Am Coll Cardiol. 2011;57(23):2379.</mixed-citation>
      </ref>
      <ref id="B123">
        <label>123</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Tendera</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Aboyans</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Bartelink</surname>
              <given-names>ML</given-names>
            </name>
            <name>
              <surname>Baumgartner</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Cl&#233;ment</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Collet</surname>
              <given-names>JP</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>ESC Committee for Practice Guidelines. ESC Guidelines on the diagnosis and treatment of peripheral artery diseases: document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries: the Task Force on the Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of Cardiology (ESC)</article-title>
          <source>Eur Heart J</source>
          <year>2011</year>
          <volume>32</volume>
          <issue>22</issue>
          <fpage>2851</fpage>
          <lpage>2906</lpage>
        </element-citation>
        <mixed-citation>123. Tendera M, Aboyans V, Bartelink ML, Baumgartner I, Cl&#233;ment D, Collet JP et al.; ESC Committee for Practice Guidelines. ESC Guidelines on the diagnosis and treatment of peripheral artery diseases: document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries: the Task Force on the Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of Cardiology (ESC). Eur Heart J. 2011;32(22):2851-906.</mixed-citation>
      </ref>
      <ref id="B124">
        <label>124</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Rich</surname>
              <given-names>MW</given-names>
            </name>
            <name>
              <surname>Chyun</surname>
              <given-names>DA</given-names>
            </name>
            <name>
              <surname>Skolnick</surname>
              <given-names>AH</given-names>
            </name>
            <name>
              <surname>Alexander</surname>
              <given-names>KP</given-names>
            </name>
            <name>
              <surname>Forman</surname>
              <given-names>DE</given-names>
            </name>
            <name>
              <surname>Kitzman</surname>
              <given-names>DW</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>American Heart Association Older Populations Committee of the Council on Clinical Cardiology, Council on Cardiovascular and Stroke Nursing, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council; American College of Cardiology; and American Geriatrics Society. Knowledge Gaps in Cardiovascular Care of the Older Adult Population: A Scientific Statement From the American Heart Association, American College of Cardiology, and American Geriatrics Society</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2016</year>
          <volume>67</volume>
          <issue>20</issue>
          <fpage>2419</fpage>
          <lpage>2440</lpage>
        </element-citation>
        <mixed-citation>124. Rich MW, Chyun DA, Skolnick AH, Alexander KP, Forman DE, Kitzman DW et al.; American Heart Association Older Populations Committee of the Council on Clinical Cardiology, Council on Cardiovascular and Stroke Nursing, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council; American College of Cardiology; and American Geriatrics Society. Knowledge Gaps in Cardiovascular Care of the Older Adult Population: A Scientific Statement From the American Heart Association, American College of Cardiology, and American Geriatrics Society. J Am Coll Cardiol. 2016;67(20):2419-40.</mixed-citation>
      </ref>
      <ref id="B125">
        <label>125</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Finlayson</surname>
              <given-names>EV</given-names>
            </name>
            <name>
              <surname>Birkmayer</surname>
              <given-names>JD</given-names>
            </name>
          </person-group>
          <article-title>Operative mortality with elective surgery in older adults</article-title>
          <source>Eff Clin Pract</source>
          <year>2001</year>
          <volume>4</volume>
          <issue>4</issue>
          <fpage>172</fpage>
          <lpage>177</lpage>
          <comment>Erratum in: Eff Clin Pract. 2001;4(5):235</comment>
        </element-citation>
        <mixed-citation>125. Finlayson EV, Birkmayer JD. Operative mortality with elective surgery in older adults. Eff Clin Pract. 2001;4(4):172-7. Erratum in: Eff Clin Pract. 2001;4(5):235.</mixed-citation>
      </ref>
      <ref id="B126">
        <label>126</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Herrera</surname>
              <given-names>AP</given-names>
            </name>
            <name>
              <surname>Snipes</surname>
              <given-names>AS</given-names>
            </name>
            <name>
              <surname>King</surname>
              <given-names>DW</given-names>
            </name>
            <name>
              <surname>Torres-Vigil</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Goldberg</surname>
              <given-names>DS</given-names>
            </name>
            <name>
              <surname>Weinberg</surname>
              <given-names>AD</given-names>
            </name>
          </person-group>
          <article-title>Disparate inclusion of older adults in clinical trials: priorities and opportunities for police and practice change</article-title>
          <source>Am J Public Health</source>
          <year>2010</year>
          <volume>100</volume>
          <supplement>Suppl 1</supplement>
          <fpage>S105</fpage>
          <lpage>S112</lpage>
        </element-citation>
        <mixed-citation>126. Herrera AP, Snipes AS, King DW, Torres-Vigil I, Goldberg DS, Weinberg AD. Disparate inclusion of older adults in clinical trials: priorities and opportunities for police and practice change. Am J Public Health. 2010;100 Suppl 1:S105-12.</mixed-citation>
      </ref>
      <ref id="B127">
        <label>127</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Baquero</surname>
              <given-names>GA</given-names>
            </name>
            <name>
              <surname>Rich</surname>
              <given-names>MW</given-names>
            </name>
          </person-group>
          <article-title>Perioperative care in older adults</article-title>
          <source>J Geriatr Cardiol</source>
          <year>2015</year>
          <volume>12</volume>
          <issue>5</issue>
          <fpage>465</fpage>
          <lpage>469</lpage>
        </element-citation>
        <mixed-citation>127. Baquero GA, Rich MW. Perioperative care in older adults. J Geriatr Cardiol. 2015;12(5):465-9.</mixed-citation>
      </ref>
      <ref id="B128">
        <label>128</label>
        <element-citation publication-type="webpage">
          <person-group person-group-type="author">
            <collab>Conselho Federal de Medicina (CFM)</collab>
          </person-group>
          <article-title>Determina&#231;&#245;es para consentimento informado</article-title>
          <date-in-citation content-type="access-date">2017 dez 10</date-in-citation>
          <comment>Dispon&#237;vel em: <ext-link ext-link-type="uri" xlink:href="https://portal.cfm.org.br/index/php?">https://portal.cfm.org.br/index/php?</ext-link></comment>
        </element-citation>
        <mixed-citation>128. Conselho Federal de Medicina (CFM). Determina&#231;&#245;es para consentimento informado. [Internet]. [Citado em 2017 dez 10]. Dispon&#237;vel em: <ext-link ext-link-type="uri" xlink:href="https://portal.cfm.org.br/index/php?">https://portal.cfm.org.br/index/php?</ext-link></mixed-citation>
      </ref>
      <ref id="B129">
        <label>129</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Wijeysundera</surname>
              <given-names>DN</given-names>
            </name>
            <name>
              <surname>Duncan</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Nkonde-Price</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Virani</surname>
              <given-names>SS</given-names>
            </name>
            <name>
              <surname>Washam</surname>
              <given-names>JB</given-names>
            </name>
            <name>
              <surname>Fleischmann</surname>
              <given-names>KE</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Perioperative beta blockade in noncardiac surgery: a systematic review for the 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2014</year>
          <volume>64</volume>
          <issue>22</issue>
          <fpage>2406</fpage>
          <lpage>2425</lpage>
        </element-citation>
        <mixed-citation>129. Wijeysundera DN, Duncan D, Nkonde-Price C, Virani SS, Washam JB, Fleischmann KE et al. Perioperative beta blockade in noncardiac surgery: a systematic review for the 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol. 2014;64(22):2406-25.</mixed-citation>
      </ref>
      <ref id="B130">
        <label>130</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Levine</surname>
              <given-names>GN</given-names>
            </name>
            <name>
              <surname>Bates</surname>
              <given-names>ER</given-names>
            </name>
            <name>
              <surname>Blankenship</surname>
              <given-names>JC</given-names>
            </name>
            <name>
              <surname>Bailey</surname>
              <given-names>SR</given-names>
            </name>
            <name>
              <surname>Bittl</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Cercek</surname>
              <given-names>B</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines; Society for Cardiovascular Angiography and Interventions. ACCF/AHA/SCA guideline for percutaneous coronary intervention: report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2011</year>
          <volume>58</volume>
          <issue>24</issue>
          <fpage>e44</fpage>
          <lpage>e122</lpage>
        </element-citation>
        <mixed-citation>130. Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B et al.; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines; Society for Cardiovascular Angiography and Interventions. ACCF/AHA/SCA guideline for percutaneous coronary intervention: report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011;58(24):e44-122.</mixed-citation>
      </ref>
      <ref id="B131">
        <label>131</label>
        <element-citation publication-type="webpage">
          <person-group person-group-type="author">
            <collab>Sociedade Brasileira de Imuniza&#231;&#245;es (SBIm)</collab>
          </person-group>
          <source>Guia de vacina&#231;&#227;o [internet]</source>
          <date-in-citation content-type="access-date">2018 jan 10</date-in-citation>
          <comment>Dispon&#237;vel em <ext-link ext-link-type="uri" xlink:href="http://sbim.org.br/images/files/guia-geriatria-sbim-sbgg-3a-ed-2016-2017-160525-web.pdf">http://sbim.org.br/images/files/guia-geriatria-sbim-sbgg-3a-ed-2016-2017-160525-web.pdf</ext-link></comment>
        </element-citation>
        <mixed-citation>131. Sociedade Brasileira de Imuniza&#231;&#245;es (SBIm). Guia de vacina&#231;&#227;o [internet]. [Citado em 2018 jan 10]. Dispon&#237;vel em <ext-link ext-link-type="uri" xlink:href="http://sbim.org.br/images/files/guia-geriatria-sbim-sbgg-3a-ed-2016-2017-160525-web.pdf">http://sbim.org.br/images/files/guia-geriatria-sbim-sbgg-3a-ed-2016-2017-160525-web.pdf</ext-link></mixed-citation>
      </ref>
      <ref id="B132">
        <label>132</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <collab>World Health Organization (WHO)</collab>
          </person-group>
          <source>Planning and implementing palliative care services: a guide for programme managers</source>
          <publisher-loc>Geneva</publisher-loc>
          <year>2016</year>
        </element-citation>
        <mixed-citation>132. World Health Organization (WHO). Planning and implementing palliative care services: a guide for programme managers. Geneva; 2016.</mixed-citation>
      </ref>
      <ref id="B133">
        <label>133</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Carvalho</surname>
              <given-names>RT</given-names>
            </name>
            <name>
              <surname>Parsons</surname>
              <given-names>HA</given-names>
            </name>
          </person-group>
          <source>Manual de cuidados paliativos da Academia Nacional de Cuidados Paliativos (ANCP)</source>
          <edition>2. ed.</edition>
          <publisher-loc>Porto Alegre</publisher-loc>
          <publisher-name>Meridional</publisher-name>
          <year>2012</year>
        </element-citation>
        <mixed-citation>133. Carvalho RT, Parsons HA. Manual de cuidados paliativos da Academia Nacional de Cuidados Paliativos (ANCP). 2. ed. Porto Alegre: Meridional; 2012.</mixed-citation>
      </ref>
      <ref id="B134">
        <label>134</label>
        <element-citation publication-type="webpage">
          <person-group person-group-type="author">
            <name>
              <surname>Fine</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>MacLow</surname>
              <given-names>C</given-names>
            </name>
          </person-group>
          <article-title>Hospice referral and care: practical guidance for clinicians</article-title>
          <date-in-citation content-type="access-date">2017 Dec 10</date-in-citation>
          <comment>Available from: <ext-link ext-link-type="uri" xlink:href="http://cme.medscape.com/viewarticle/487401">http://cme.medscape.com/viewarticle/487401</ext-link></comment>
        </element-citation>
        <mixed-citation>134. Fine, P. MacLow C. Hospice referral and care: practical guidance for clinicians. [Internet]. [Cited in 2017 Dec 10]. Available from: <ext-link ext-link-type="uri" xlink:href="http://cme.medscape.com/viewarticle/487401">http://cme.medscape.com/viewarticle/487401</ext-link>.</mixed-citation>
      </ref>
      <ref id="B135">
        <label>135</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Wei</surname>
              <given-names>JY</given-names>
            </name>
            <name>
              <surname>Gersh</surname>
              <given-names>BJ</given-names>
            </name>
          </person-group>
          <article-title>Heart disease in the elderly</article-title>
          <source>Curr Probl Cardiol</source>
          <year>1987</year>
          <volume>12</volume>
          <issue>1</issue>
          <fpage>1</fpage>
          <lpage>65</lpage>
        </element-citation>
        <mixed-citation>135. Wei JY, Gersh BJ. Heart disease in the elderly. Curr Probl Cardiol. 1987;12(1):1-65.</mixed-citation>
      </ref>
      <ref id="B136">
        <label>136</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Molander</surname>
              <given-names>U</given-names>
            </name>
            <name>
              <surname>Dey</surname>
              <given-names>DK</given-names>
            </name>
            <name>
              <surname>Sundh</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Steen</surname>
              <given-names>B</given-names>
            </name>
          </person-group>
          <article-title>ECG abnormalities in the elderly: prevalence, time and generation trends and association with mortality</article-title>
          <source>Aging Clin Exp Res</source>
          <year>2003</year>
          <volume>15</volume>
          <issue>6</issue>
          <fpage>488</fpage>
          <lpage>493</lpage>
        </element-citation>
        <mixed-citation>136. Molander U, Dey DK, Sundh V, Steen B. ECG abnormalities in the elderly: prevalence, time and generation trends and association with mortality. Aging Clin Exp Res. 2003;15(6):488-93.</mixed-citation>
      </ref>
      <ref id="B137">
        <label>137</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Diamond</surname>
              <given-names>GA</given-names>
            </name>
            <name>
              <surname>Forrester</surname>
              <given-names>JS</given-names>
            </name>
          </person-group>
          <article-title>Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease</article-title>
          <source>N Engl J Med</source>
          <year>1979</year>
          <volume>300</volume>
          <issue>24</issue>
          <fpage>1350</fpage>
          <lpage>1358</lpage>
        </element-citation>
        <mixed-citation>137. Diamond GA, Forrester JS. Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease. N Engl J Med. 1979;300(24):1350-8.</mixed-citation>
      </ref>
      <ref id="B138">
        <label>138</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Katsikis</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Theodorakos</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Kouzoumi</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Papaioannou</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Drosatos</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Koutelou</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
          <article-title>Prognostic value of the Duke treadmill score in octogenarians undergoing myocardial perfusion imaging</article-title>
          <source>Atherosclerosis</source>
          <year>2014</year>
          <volume>236</volume>
          <issue>2</issue>
          <fpage>373</fpage>
          <lpage>380</lpage>
        </element-citation>
        <mixed-citation>138. Katsikis A, Theodorakos A, Kouzoumi A, Papaioannou S, Drosatos A, Koutelou M. Prognostic value of the Duke treadmill score in octogenarians undergoing myocardial perfusion imaging. Atherosclerosis. 2014;236(2):373-80.</mixed-citation>
      </ref>
      <ref id="B139">
        <label>139</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Rai</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Baker</surname>
              <given-names>WL</given-names>
            </name>
            <name>
              <surname>Parker</surname>
              <given-names>MW</given-names>
            </name>
            <name>
              <surname>Heller</surname>
              <given-names>GV</given-names>
            </name>
          </person-group>
          <article-title>Meta-analysis of optimal risk stratification in patients &gt; 65 years of age</article-title>
          <source>Am J Cardiol</source>
          <year>2012</year>
          <volume>110</volume>
          <issue>8</issue>
          <fpage>1092</fpage>
          <lpage>1099</lpage>
        </element-citation>
        <mixed-citation>139. Rai M, Baker WL, Parker MW, Heller GV. Meta-analysis of optimal risk stratification in patients &gt; 65 years of age. Am J Cardiol. 2012;110(8):1092-9.</mixed-citation>
      </ref>
      <ref id="B140">
        <label>140</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Oliveira</surname>
              <given-names>JL</given-names>
            </name>
            <name>
              <surname>G&#243;es</surname>
              <given-names>TJ</given-names>
            </name>
            <name>
              <surname>Santana</surname>
              <given-names>TA</given-names>
            </name>
            <name>
              <surname>Silva</surname>
              <given-names>IS</given-names>
            </name>
            <name>
              <surname>Travassos</surname>
              <given-names>TF</given-names>
            </name>
            <name>
              <surname>Teles</surname>
              <given-names>LD</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Exercise stress echocardiography in the identification of coronary artery disease in the elderly with chronotropic incompetence</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2007</year>
          <volume>89</volume>
          <issue>2</issue>
          <fpage>100-6</fpage>
          <lpage>111-8</lpage>
        </element-citation>
        <mixed-citation>140. Oliveira JL, G&#243;es TJ, Santana TA, Silva IS, Travassos TF, Teles LD et al. Exercise stress echocardiography in the identification of coronary artery disease in the elderly with chronotropic incompetence. Arq Bras Cardiol. 2007;89(2):100-6, 111-8.</mixed-citation>
      </ref>
      <ref id="B141">
        <label>141</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Tota-Maharaj</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Blaha</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>McEvoy</surname>
              <given-names>JW</given-names>
            </name>
            <name>
              <surname>Blumenthal</surname>
              <given-names>RS</given-names>
            </name>
            <name>
              <surname>Muse</surname>
              <given-names>ED</given-names>
            </name>
            <name>
              <surname>Budoff</surname>
              <given-names>MJ</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Coronary artery calcium for the prediction of mortality in young adults &lt; 45 years old and elderly adults &gt; 75 years old</article-title>
          <source>Eur Heart J</source>
          <year>2012</year>
          <volume>33</volume>
          <issue>23</issue>
          <fpage>2955</fpage>
          <lpage>2962</lpage>
        </element-citation>
        <mixed-citation>141. Tota-Maharaj R, Blaha MJ, McEvoy JW, Blumenthal RS, Muse ED, Budoff MJ, et al. Coronary artery calcium for the prediction of mortality in young adults &lt; 45 years old and elderly adults &gt; 75 years old. Eur Heart J. 2012;33(23):2955-62.</mixed-citation>
      </ref>
      <ref id="B142">
        <label>142</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Chan</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>Liew</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Chin</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Sim</surname>
              <given-names>KH</given-names>
            </name>
          </person-group>
          <article-title>Feasibility and accuracy of coronary imaging in elderly patients using the 64-row muItidetector computed tomography: a correlation study with conventionaI coronary angiography</article-title>
          <source>J Geriatr Cardiol</source>
          <year>2006</year>
          <volume>3</volume>
          <issue>1</issue>
          <fpage>9</fpage>
          <lpage>14</lpage>
        </element-citation>
        <mixed-citation>142. Chan W, Liew C, Chin S, Sim KH. Feasibility and accuracy of coronary imaging in elderly patients using the 64-row muItidetector computed tomography: a correlation study with conventionaI coronary angiography. J Geriatr Cardiol. 2006;3(1):9-14.</mixed-citation>
      </ref>
      <ref id="B143">
        <label>143</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>de Lorgeril</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Salen</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Martin</surname>
              <given-names>JL</given-names>
            </name>
            <name>
              <surname>Monjaud</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Delaye</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Mamelle</surname>
              <given-names>N</given-names>
            </name>
          </person-group>
          <article-title>Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study</article-title>
          <source>Circulation</source>
          <year>1999</year>
          <volume>99</volume>
          <issue>6</issue>
          <fpage>779</fpage>
          <lpage>785</lpage>
        </element-citation>
        <mixed-citation>143. de Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation. 1999;99(6):779-85.</mixed-citation>
      </ref>
      <ref id="B144">
        <label>144</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Sacks</surname>
              <given-names>FM</given-names>
            </name>
            <name>
              <surname>Svetkey</surname>
              <given-names>LP</given-names>
            </name>
            <name>
              <surname>Vollmer</surname>
              <given-names>WM</given-names>
            </name>
            <name>
              <surname>Appel</surname>
              <given-names>LJ</given-names>
            </name>
            <name>
              <surname>Bray</surname>
              <given-names>GA</given-names>
            </name>
            <name>
              <surname>Harsha</surname>
              <given-names>D</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>DASH-Sodium Collaborative Research Group. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group</article-title>
          <source>N Engl J Med</source>
          <year>2001</year>
          <volume>344</volume>
          <issue>1</issue>
          <fpage>3</fpage>
          <lpage>10</lpage>
        </element-citation>
        <mixed-citation>144. Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D et al.; DASH-Sodium Collaborative Research Group. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001;344(1):3-10.</mixed-citation>
      </ref>
      <ref id="B145">
        <label>145</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Estruch</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Ros</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Salas-Salvado</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Covas</surname>
              <given-names>MI</given-names>
            </name>
            <name>
              <surname>Corella</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Ar&#243;s</surname>
              <given-names>F</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet</article-title>
          <source>N Engl J Med</source>
          <year>2013</year>
          <volume>368</volume>
          <issue>14</issue>
          <fpage>1279</fpage>
          <lpage>1290</lpage>
          <comment>Erratum in: N Engl J Med. 2014;370(9):886</comment>
        </element-citation>
        <mixed-citation>145. Estruch R, Ros E, Salas-Salvado J, Covas MI, Corella D, Ar&#243;s F et al.; PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;368(14):1279-90. Erratum in: N Engl J Med. 2014;370(9):886.</mixed-citation>
      </ref>
      <ref id="B146">
        <label>146</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Akin</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>T&#246;lg</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Hochadel</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Bergmann</surname>
              <given-names>MW</given-names>
            </name>
            <name>
              <surname>Khattab</surname>
              <given-names>AA</given-names>
            </name>
            <name>
              <surname>Schneider</surname>
              <given-names>S</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>DES.DE (German Drug-Eluting Stent) Study Group. No evidence of &#8220;obesity paradox&#8221; after treatment with drug-eluting stents in a routine clinical practice: results from the prospective multicenter German DES.DE (German Drug-Eluting Stent) Registry</article-title>
          <source>JACC Cardiovasc Interv</source>
          <year>2012</year>
          <volume>5</volume>
          <issue>2</issue>
          <fpage>162</fpage>
          <lpage>169</lpage>
        </element-citation>
        <mixed-citation>146. Akin I, T&#246;lg R, Hochadel M, Bergmann MW, Khattab AA, Schneider S et al. DES.DE (German Drug-Eluting Stent) Study Group. No evidence of &#8220;obesity paradox&#8221; after treatment with drug-eluting stents in a routine clinical practice: results from the prospective multicenter German DES.DE (German Drug-Eluting Stent) Registry. JACC Cardiovasc Interv. 2012;5(2):162-9.</mixed-citation>
      </ref>
      <ref id="B147">
        <label>147</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Gnanasekaran</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Biedenbender</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Davidson</surname>
              <given-names>HE</given-names>
            </name>
            <name>
              <surname>Gravenstein</surname>
              <given-names>S</given-names>
            </name>
          </person-group>
          <article-title>Vaccinations for the older adult</article-title>
          <source>Clin Geriatr Med</source>
          <year>2016</year>
          <volume>32</volume>
          <issue>3</issue>
          <fpage>609</fpage>
          <lpage>625</lpage>
        </element-citation>
        <mixed-citation>147. Gnanasekaran G, Biedenbender R, Davidson HE, Gravenstein S. Vaccinations for the older adult. Clin Geriatr Med. 2016;32(3):609-25.</mixed-citation>
      </ref>
      <ref id="B148">
        <label>148</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Hermanson</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Omenn</surname>
              <given-names>GS</given-names>
            </name>
            <name>
              <surname>Kronmal</surname>
              <given-names>RA</given-names>
            </name>
            <name>
              <surname>Gersh</surname>
              <given-names>BJ</given-names>
            </name>
          </person-group>
          <article-title>Beneficial six-year outcome of smoking cessation in older men and women with coronary artery disease. Results from the CASS registry</article-title>
          <source>N Engl J Med</source>
          <year>1988</year>
          <volume>319</volume>
          <issue>21</issue>
          <fpage>1365</fpage>
          <lpage>1369</lpage>
        </element-citation>
        <mixed-citation>148. Hermanson B, Omenn GS, Kronmal RA, Gersh BJ. Beneficial six-year outcome of smoking cessation in older men and women with coronary artery disease. Results from the CASS registry. N Engl J Med. 1988;319(21):1365-9.</mixed-citation>
      </ref>
      <ref id="B149">
        <label>149</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Wright</surname>
              <given-names>JT</given-names>
              <suffix>Jr</suffix>
            </name>
            <name>
              <surname>Williamson</surname>
              <given-names>JD</given-names>
            </name>
            <name>
              <surname>Whelton</surname>
              <given-names>PK</given-names>
            </name>
            <name>
              <surname>Snyder</surname>
              <given-names>JK</given-names>
            </name>
            <name>
              <surname>Sink</surname>
              <given-names>KM</given-names>
            </name>
            <name>
              <surname>Rocco</surname>
              <given-names>MV</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control</article-title>
          <source>N Engl J Med</source>
          <year>2015</year>
          <volume>373</volume>
          <issue>22</issue>
          <fpage>2103</fpage>
          <lpage>2116</lpage>
        </element-citation>
        <mixed-citation>149. Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV et al.; SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373(22):2103-16.</mixed-citation>
      </ref>
      <ref id="B150">
        <label>150</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Dai</surname>
              <given-names>X</given-names>
            </name>
            <name>
              <surname>Busby-Whitehead</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Forman</surname>
              <given-names>DE</given-names>
            </name>
            <name>
              <surname>Alexander</surname>
              <given-names>KP</given-names>
            </name>
          </person-group>
          <article-title>Stable ischemic heart disease in the older adults</article-title>
          <source>J Geriatr Cardiol</source>
          <year>2016</year>
          <volume>13</volume>
          <issue>2</issue>
          <fpage>109</fpage>
          <lpage>114</lpage>
        </element-citation>
        <mixed-citation>150. Dai X, Busby-Whitehead J, Forman DE, Alexander KP. Stable ischemic heart disease in the older adults. J Geriatr Cardiol. 2016;13(2):109-14.</mixed-citation>
      </ref>
      <ref id="B151">
        <label>151</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Pfisterer</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Buser</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Osswald</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Allemann</surname>
              <given-names>U</given-names>
            </name>
            <name>
              <surname>Amann</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>Angehrn</surname>
              <given-names>W</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Trial of Invasive versus Medical therapy in Elderly patients (TIME) Investigators. Outcome of elderly patients with chronic symptomatic coronary artery disease with an invasive versus optimized medical treatment strategy: one-year results of the randomized TIME trial</article-title>
          <source>JAMA</source>
          <year>2003</year>
          <volume>289</volume>
          <issue>9</issue>
          <fpage>1117</fpage>
          <lpage>1123</lpage>
        </element-citation>
        <mixed-citation>151. Pfisterer M, Buser P, Osswald S, Allemann U, Amann W, Angehrn W et al.; Trial of Invasive versus Medical therapy in Elderly patients (TIME) Investigators. Outcome of elderly patients with chronic symptomatic coronary artery disease with an invasive versus optimized medical treatment strategy: one-year results of the randomized TIME trial. JAMA. 2003;289(9):1117-23.</mixed-citation>
      </ref>
      <ref id="B152">
        <label>152</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Metha</surname>
              <given-names>RH</given-names>
            </name>
            <name>
              <surname>Rathore</surname>
              <given-names>SS</given-names>
            </name>
            <name>
              <surname>Radford</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Wang</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Krumholz</surname>
              <given-names>HM</given-names>
            </name>
          </person-group>
          <article-title>Acute myocardial infarction in the elderly: differences by age</article-title>
          <source>J Am Col Cardiol</source>
          <year>2001</year>
          <volume>38</volume>
          <issue>3</issue>
          <fpage>736</fpage>
          <lpage>741</lpage>
        </element-citation>
        <mixed-citation>152. Metha RH, Rathore SS, Radford MJ, Wang Y, Krumholz HM. Acute myocardial infarction in the elderly: differences by age. J Am Col Cardiol. 2001;38(3):736-41.</mixed-citation>
      </ref>
      <ref id="B153">
        <label>153</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Alexander</surname>
              <given-names>KP</given-names>
            </name>
            <name>
              <surname>Newby</surname>
              <given-names>LK</given-names>
            </name>
            <name>
              <surname>Cannor</surname>
              <given-names>CP</given-names>
            </name>
            <name>
              <surname>Armstrong</surname>
              <given-names>PW</given-names>
            </name>
            <name>
              <surname>Gibler</surname>
              <given-names>WB</given-names>
            </name>
            <name>
              <surname>Rich</surname>
              <given-names>MW</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>American Heart Association Council on Clinical Cardiology; Society of Geriatric Cardiology. Acute coronary care in the elderly: part I: Non-ST-segment-elevation acute coronary syndromes: a scientific statement for healthcare professionals from the American Heart Association Council on Clinical Cardiology: in collaboration with the Society of Geriatric Cardiology</article-title>
          <source>Circulation</source>
          <year>2007</year>
          <volume>115</volume>
          <issue>19</issue>
          <fpage>2549</fpage>
          <lpage>2569</lpage>
        </element-citation>
        <mixed-citation>153. Alexander KP, Newby LK, Cannor CP, Armstrong PW, Gibler WB, Rich MW et al.; American Heart Association Council on Clinical Cardiology; Society of Geriatric Cardiology. Acute coronary care in the elderly: part I: Non-ST-segment-elevation acute coronary syndromes: a scientific statement for healthcare professionals from the American Heart Association Council on Clinical Cardiology: in collaboration with the Society of Geriatric Cardiology. Circulation. 2007;115(19):2549-69.</mixed-citation>
      </ref>
      <ref id="B154">
        <label>154</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Alexander</surname>
              <given-names>KP</given-names>
            </name>
            <name>
              <surname>Newby</surname>
              <given-names>LK</given-names>
            </name>
            <name>
              <surname>Cannor</surname>
              <given-names>CP</given-names>
            </name>
            <name>
              <surname>Armstrong</surname>
              <given-names>PW</given-names>
            </name>
            <name>
              <surname>Gibler</surname>
              <given-names>WB</given-names>
            </name>
            <name>
              <surname>Rich</surname>
              <given-names>MW</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>American Heart Association Council on Clinical Cardiology; Society of Geriatric Cardiology. part II: ST-segment-elevation myocardial infarction: a scientific statement for healthcare professionals from the American Heart Association Council on Clinical Cardiology: in collaboration with the Society of Geriatric Cardiology</article-title>
          <source>Circulation</source>
          <year>2007</year>
          <volume>115</volume>
          <issue>19</issue>
          <fpage>2570</fpage>
          <lpage>2589</lpage>
        </element-citation>
        <mixed-citation>154. Alexander KP, Newby LK, Cannor CP, Armstrong PW, Gibler WB, Rich MW et al.; American Heart Association Council on Clinical Cardiology; Society of Geriatric Cardiology. part II: ST-segment-elevation myocardial infarction: a scientific statement for healthcare professionals from the American Heart Association Council on Clinical Cardiology: in collaboration with the Society of Geriatric Cardiology. Circulation. 2007;115(19):2570-89.</mixed-citation>
      </ref>
      <ref id="B155">
        <label>155</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Saunderson</surname>
              <given-names>CE</given-names>
            </name>
            <name>
              <surname>Brogan</surname>
              <given-names>RA</given-names>
            </name>
            <name>
              <surname>Simms</surname>
              <given-names>AD</given-names>
            </name>
            <name>
              <surname>Sutton</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Batin</surname>
              <given-names>PD</given-names>
            </name>
            <name>
              <surname>Gale</surname>
              <given-names>CP</given-names>
            </name>
          </person-group>
          <article-title>Acute coronary syndrome management in older adults: guidelines, temporal changes and challenges</article-title>
          <source>Age Ageing</source>
          <year>2014</year>
          <volume>43</volume>
          <issue>4</issue>
          <fpage>450</fpage>
          <lpage>455</lpage>
        </element-citation>
        <mixed-citation>155. Saunderson CE, Brogan RA, Simms AD, Sutton G, Batin PD, Gale CP. Acute coronary syndrome management in older adults: guidelines, temporal changes and challenges. Age Ageing. 2014;43(4):450-5.</mixed-citation>
      </ref>
      <ref id="B156">
        <label>156</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Piegas</surname>
              <given-names>LS</given-names>
            </name>
            <name>
              <surname>Timerman</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Feitosa</surname>
              <given-names>GS</given-names>
            </name>
            <name>
              <surname>Nicolau</surname>
              <given-names>JC</given-names>
            </name>
            <name>
              <surname>Mattos</surname>
              <given-names>LAP</given-names>
            </name>
            <name>
              <surname>Andrade</surname>
              <given-names>MD</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Sociedade Brasileira de Cardiologia. V Diretriz da Sociedade Brasileira de Cardiologia sobre tratamento do infarto agudo do mioc&#225;rdio com supradesn&#237;vel do segmento ST</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2015</year>
          <volume>105</volume>
          <issue>2</issue>
          <fpage>1</fpage>
          <lpage>105</lpage>
        </element-citation>
        <mixed-citation>156. Piegas LS, Timerman A, Feitosa GS, Nicolau JC, Mattos LAP, Andrade MD et al.; Sociedade Brasileira de Cardiologia. V Diretriz da Sociedade Brasileira de Cardiologia sobre tratamento do infarto agudo do mioc&#225;rdio com supradesn&#237;vel do segmento ST. Arq Bras Cardiol. 2015;105(2):1-105.</mixed-citation>
      </ref>
      <ref id="B157">
        <label>157</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Nicolau</surname>
              <given-names>JC</given-names>
            </name>
            <name>
              <surname>Timerman</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Marin</surname>
              <given-names>JA</given-names>
              <suffix>Neto</suffix>
            </name>
            <name>
              <surname>Piegas</surname>
              <given-names>LS</given-names>
            </name>
            <name>
              <surname>Barbosa</surname>
              <given-names>CJ</given-names>
            </name>
            <name>
              <surname>Franci</surname>
              <given-names>A</given-names>
            </name>
            <collab>Sociedade Brasileira de Cardiologia</collab>
          </person-group>
          <article-title>Guidelines of Sociedade Brasileira de Cardiologia for unstable angina and non-ST-segment elevation myocardial infarction (II edition, 2007) 2013-2014 update</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2014</year>
          <volume>102</volume>
          <supplement>3 Suppl 1</supplement>
          <fpage>1</fpage>
          <lpage>61</lpage>
        </element-citation>
        <mixed-citation>157. Nicolau JC, Timerman A, Marin-Neto JA, Piegas LS, Barbosa CJ, Franci A; Sociedade Brasileira de Cardiologia. [Guidelines of Sociedade Brasileira de Cardiologia for unstable angina and non-ST-segment elevation myocardial infarction (II edition, 2007) 2013-2014 update]. Arq Bras Cardiol. 2014;102(3 Suppl 1):1-61.</mixed-citation>
      </ref>
      <ref id="B158">
        <label>158</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Zhang</surname>
              <given-names>SJ</given-names>
            </name>
            <name>
              <surname>Wang</surname>
              <given-names>Q</given-names>
            </name>
            <name>
              <surname>Cui</surname>
              <given-names>YJ</given-names>
            </name>
            <name>
              <surname>Wu</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>Zhao</surname>
              <given-names>QH</given-names>
            </name>
            <name>
              <surname>Xu</surname>
              <given-names>Y</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>High-sensitivity cardiac troponin T in geriatric inpatients</article-title>
          <source>Arch Gerontol Geriatr</source>
          <year>2016</year>
          <season>Jul-Aug</season>
          <volume>65</volume>
          <fpage>111</fpage>
          <lpage>115</lpage>
        </element-citation>
        <mixed-citation>158. Zhang SJ, Wang Q, Cui YJ, Wu W, Zhao QH, Xu Y, et al. High-sensitivity cardiac troponin T in geriatric inpatients Arch Gerontol Geriatr. 2016 Jul-Aug;65:111-5.</mixed-citation>
      </ref>
      <ref id="B159">
        <label>159</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Dai</surname>
              <given-names>X</given-names>
            </name>
            <name>
              <surname>Busby-Whitehead</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Alexander</surname>
              <given-names>KP</given-names>
            </name>
          </person-group>
          <article-title>Acute coronary syndrome in older adults</article-title>
          <source>J Geriatr Cardiol</source>
          <year>2016</year>
          <volume>13</volume>
          <issue>2</issue>
          <fpage>101</fpage>
          <lpage>108</lpage>
        </element-citation>
        <mixed-citation>159. Dai X, Busby-Whitehead J, Alexander KP. Acute coronary syndrome in older adults J Geriatr Cardiol. 2016;13(2):101-8.</mixed-citation>
      </ref>
      <ref id="B160">
        <label>160</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Antman</surname>
              <given-names>EM</given-names>
            </name>
            <name>
              <surname>Cohen</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Bernink</surname>
              <given-names>PJ</given-names>
            </name>
            <name>
              <surname>McCabe</surname>
              <given-names>CH</given-names>
            </name>
            <name>
              <surname>Horacek</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Papuchis</surname>
              <given-names>G</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making</article-title>
          <source>JAMA</source>
          <year>2000</year>
          <volume>284</volume>
          <issue>7</issue>
          <fpage>835</fpage>
          <lpage>842</lpage>
        </element-citation>
        <mixed-citation>160. Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G, et al. The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA. 2000;284(7):835-42.</mixed-citation>
      </ref>
      <ref id="B161">
        <label>161</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Backus</surname>
              <given-names>BE</given-names>
            </name>
            <name>
              <surname>Six</surname>
              <given-names>AJ</given-names>
            </name>
            <name>
              <surname>Kelder</surname>
              <given-names>JH</given-names>
            </name>
            <name>
              <surname>Gibler</surname>
              <given-names>WB</given-names>
            </name>
            <name>
              <surname>Moll</surname>
              <given-names>FL</given-names>
            </name>
            <name>
              <surname>Doevendans</surname>
              <given-names>PA</given-names>
            </name>
          </person-group>
          <article-title>Risk scores for patients with chest pain: evaluation in the emergency department</article-title>
          <source>Curr Cardiol Rev</source>
          <year>2011</year>
          <volume>7</volume>
          <issue>1</issue>
          <fpage>2</fpage>
          <lpage>8</lpage>
        </element-citation>
        <mixed-citation>161. Backus BE, Six AJ, Kelder JH, Gibler WB, Moll FL, Doevendans PA. Risk scores for patients with chest pain: evaluation in the emergency department. Curr Cardiol Rev. 2011;7(1):2-8.</mixed-citation>
      </ref>
      <ref id="B162">
        <label>162</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Angeli</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Cavallini</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Verdecchia</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Morici</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Del Pinto</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Petronio</surname>
              <given-names>AS</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>A risk score for predicting 1-year mortality in patients &#8805; 75 years of age presenting with non-ST-elevation acute coronary syndrome</article-title>
          <source>Am J Cardiol</source>
          <year>2015</year>
          <volume>116</volume>
          <issue>2</issue>
          <fpage>208</fpage>
          <lpage>213</lpage>
        </element-citation>
        <mixed-citation>162. Angeli F, Cavallini C, Verdecchia P, Morici N, Del Pinto M, Petronio AS et al. A risk score for predicting 1-year mortality in patients &#8805; 75 years of age presenting with non-ST-elevation acute coronary syndrome. Am J Cardiol. 2015;116(2):208-13.</mixed-citation>
      </ref>
      <ref id="B163">
        <label>163</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Roe</surname>
              <given-names>MT</given-names>
            </name>
            <name>
              <surname>Chen</surname>
              <given-names>AY</given-names>
            </name>
            <name>
              <surname>Thomas</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Wang</surname>
              <given-names>TY</given-names>
            </name>
            <name>
              <surname>Alexander</surname>
              <given-names>KP</given-names>
            </name>
            <name>
              <surname>Hammill</surname>
              <given-names>BG</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Predicting long-term mortality in older patients after non-ST-segment elevation myocardial infarction: the CRUZADE long-term mortality model and risk score</article-title>
          <source>Am Heart J</source>
          <year>2011</year>
          <volume>162</volume>
          <issue>5</issue>
          <fpage>875</fpage>
          <lpage>883</lpage>
        </element-citation>
        <mixed-citation>163. Roe MT, Chen AY, Thomas L, Wang TY, Alexander KP, Hammill BG et al. Predicting long-term mortality in older patients after non-ST-segment elevation myocardial infarction: the CRUZADE long-term mortality model and risk score. Am Heart J. 2011;162(5):875-83.</mixed-citation>
      </ref>
      <ref id="B164">
        <label>164</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ekerstad</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Swahn</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Janzon</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Alfredsson</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>L&#246;fmark</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Lindenberger</surname>
              <given-names>M</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Frailty is independently associated with short-term outcomes for elderly patients with non-ST-segment elevation myocardial infarction</article-title>
          <source>Circulation</source>
          <year>2011</year>
          <volume>124</volume>
          <issue>22</issue>
          <fpage>397</fpage>
          <lpage>2404</lpage>
        </element-citation>
        <mixed-citation>164. Ekerstad N, Swahn E, Janzon M, Alfredsson J, L&#246;fmark R, Lindenberger M et al. Frailty is independently associated with short-term outcomes for elderly patients with non-ST-segment elevation myocardial infarction. Circulation. 2011;124(22):397-2404.</mixed-citation>
      </ref>
      <ref id="B165">
        <label>165</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ariza-Sole</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Formiga</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Lorente</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>S&#225;nchez-Salado</surname>
              <given-names>JC</given-names>
            </name>
            <name>
              <surname>S&#225;nchez-Elvira</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Roura</surname>
              <given-names>G</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Efficacy of bleeding risk scores in elderly patients with acute coronary syndromes</article-title>
          <source>Rev Esp Cardiol (Engl Ed)</source>
          <year>2014</year>
          <volume>67</volume>
          <issue>6</issue>
          <fpage>463</fpage>
          <lpage>470</lpage>
        </element-citation>
        <mixed-citation>165. Ariza-Sole A, Formiga F, Lorente V, S&#225;nchez-Salado JC, S&#225;nchez-Elvira G, Roura G et al. Efficacy of bleeding risk scores in elderly patients with acute coronary syndromes. Rev Esp Cardiol (Engl Ed) 2014;67(6):463-70.</mixed-citation>
      </ref>
      <ref id="B166">
        <label>166</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Decourcelle</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Marecahux</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Pin&#231;on</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Barrailler</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Le Jemtel</surname>
              <given-names>TH</given-names>
            </name>
            <name>
              <surname>Ennezat</surname>
              <given-names>PV</given-names>
            </name>
          </person-group>
          <article-title>Impact of functional decline on outcome in elderly patients with acute coronary syndromes</article-title>
          <source>Am J Crit Care</source>
          <year>2013</year>
          <volume>22</volume>
          <issue>1</issue>
          <fpage>e1</fpage>
          <lpage>e11</lpage>
        </element-citation>
        <mixed-citation>166. Decourcelle V, Marecahux S, Pin&#231;on C, Barrailler S, Le Jemtel TH, Ennezat PV. Impact of functional decline on outcome in elderly patients with acute coronary syndromes. Am J Crit Care. 2013;22(1):e1-11.</mixed-citation>
      </ref>
      <ref id="B167">
        <label>167</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Moretti</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Quadri</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>D`Ascenzo</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Bertaina</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Giusto</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Marra</surname>
              <given-names>S</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>THE STORM (acute coronary syndrome in patients end of life and risk assesment ) study</article-title>
          <source>Emerg Med J</source>
          <year>2016</year>
          <volume>33</volume>
          <issue>1</issue>
          <fpage>10</fpage>
          <lpage>16</lpage>
        </element-citation>
        <mixed-citation>167. Moretti C, Quadri G, D`Ascenzo F, Bertaina M, Giusto F, Marra S et al. THE STORM (acute coronary syndrome in patients end of life and risk assesment ) study. Emerg Med J. 2016;33(1):10-6.</mixed-citation>
      </ref>
      <ref id="B168">
        <label>168</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>O&#8217;Gara</surname>
              <given-names>PT</given-names>
            </name>
            <name>
              <surname>Kushner</surname>
              <given-names>FG</given-names>
            </name>
            <name>
              <surname>Ascheim</surname>
              <given-names>DD</given-names>
            </name>
            <name>
              <surname>Casey</surname>
              <given-names>DE</given-names>
              <suffix>Jr</suffix>
            </name>
            <name>
              <surname>Chung</surname>
              <given-names>MK</given-names>
            </name>
            <name>
              <surname>de Lemos</surname>
              <given-names>JA</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines</article-title>
          <source>Circulation</source>
          <year>2013</year>
          <volume>127</volume>
          <issue>4</issue>
          <fpage>e362</fpage>
          <lpage>e425</lpage>
        </element-citation>
        <mixed-citation>168. O&#8217;Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA et al.; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(4):e362-425.</mixed-citation>
      </ref>
      <ref id="B169">
        <label>169</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Roffi</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Patrono</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Collet</surname>
              <given-names>JP</given-names>
            </name>
            <name>
              <surname>Mueller</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Valgimigli</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Andreotti</surname>
              <given-names>F</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC)</article-title>
          <source>Eur Heart J</source>
          <year>2016</year>
          <volume>37</volume>
          <issue>3</issue>
          <fpage>267</fpage>
          <lpage>315</lpage>
        </element-citation>
        <mixed-citation>169. Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37(3):267-315.</mixed-citation>
      </ref>
      <ref id="B170">
        <label>170</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Steg</surname>
              <given-names>PG</given-names>
            </name>
            <name>
              <surname>James</surname>
              <given-names>SK</given-names>
            </name>
            <name>
              <surname>Atar</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Badano</surname>
              <given-names>LP</given-names>
            </name>
            <name>
              <surname>Blomstrom-Lundqvist</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Borger</surname>
              <given-names>MA</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation</article-title>
          <source>Eur Heart J</source>
          <year>2012</year>
          <volume>33</volume>
          <issue>20</issue>
          <fpage>2569</fpage>
          <lpage>2619</lpage>
        </element-citation>
        <mixed-citation>170. Steg PG, James SK, Atar D, Badano LP, Blomstrom-Lundqvist C, Borger MA et al.; Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012;33(20):2569-619.</mixed-citation>
      </ref>
      <ref id="B171">
        <label>171</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Gale</surname>
              <given-names>CP</given-names>
            </name>
            <name>
              <surname>Cattle</surname>
              <given-names>BA</given-names>
            </name>
            <name>
              <surname>Woolston</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Baxter</surname>
              <given-names>PD</given-names>
            </name>
            <name>
              <surname>West</surname>
              <given-names>TH</given-names>
            </name>
            <name>
              <surname>Simms</surname>
              <given-names>AD</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Resolving inequalities in care? Reduced mortality in the elderly after acute coronary syndromes. The Myocardial Ischaemia National Audit Project 2003&#8211;2010</article-title>
          <source>Eur Heart J</source>
          <year>2012</year>
          <volume>33</volume>
          <issue>5</issue>
          <fpage>630</fpage>
          <lpage>639</lpage>
        </element-citation>
        <mixed-citation>171. Gale CP, Cattle BA, Woolston A, Baxter PD, West TH, Simms AD et al. Resolving inequalities in care? Reduced mortality in the elderly after acute coronary syndromes. The Myocardial Ischaemia National Audit Project 2003&#8211;2010. Eur Heart J. 2012;33(5):630-9.</mixed-citation>
      </ref>
      <ref id="B172">
        <label>172</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Deedwania</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Stone</surname>
              <given-names>PH</given-names>
            </name>
            <name>
              <surname>Bairey Merz</surname>
              <given-names>CN</given-names>
            </name>
            <name>
              <surname>Cosin-Aguilar</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Koylan</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Luo</surname>
              <given-names>D</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Effects of intensive versus moderate lipid-lowering therapy on myocardial ischemia in older patients with coronary heart disease: results of the Study Assessing Goals in the Elderly (SAGE)</article-title>
          <source>Circulation</source>
          <year>2007</year>
          <volume>115</volume>
          <issue>6</issue>
          <fpage>700</fpage>
          <lpage>707</lpage>
        </element-citation>
        <mixed-citation>172. Deedwania P, Stone PH, Bairey Merz CN, Cosin-Aguilar J, Koylan N, Luo D et al. Effects of intensive versus moderate lipid-lowering therapy on myocardial ischemia in older patients with coronary heart disease: results of the Study Assessing Goals in the Elderly (SAGE). Circulation. 2007;115(6):700-7.</mixed-citation>
      </ref>
      <ref id="B173">
        <label>173</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Carro</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Kaski</surname>
              <given-names>JC</given-names>
            </name>
          </person-group>
          <article-title>Myocardial infarction in the elderly</article-title>
          <source>Aging Dis</source>
          <year>2011</year>
          <volume>2</volume>
          <issue>2</issue>
          <fpage>116</fpage>
          <lpage>137</lpage>
        </element-citation>
        <mixed-citation>173. Carro A, Kaski JC. Myocardial infarction in the elderly. Aging Dis. 2011;2(2):116-37.</mixed-citation>
      </ref>
      <ref id="B174">
        <label>174</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Tegn</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Abdelnoor</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Aaberge</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Endresen</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Smith</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Aakhus</surname>
              <given-names>S</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>After Eighty study investigators. Invasive versus conservative strategy in patients aged 80 years or older with non ST elevation myocardial infarction or unstable angina pectoris (after Eighty Study); an open-label randomised trial</article-title>
          <source>Lancet</source>
          <year>2016</year>
          <volume>387</volume>
          <issue>10023</issue>
          <fpage>1057</fpage>
          <lpage>1065</lpage>
        </element-citation>
        <mixed-citation>174. Tegn N, Abdelnoor M, Aaberge L, Endresen K, Smith P, Aakhus S et al.; After Eighty study investigators. Invasive versus conservative strategy in patients aged 80 years or older with non ST elevation myocardial infarction or unstable angina pectoris (after Eighty Study); an open-label randomised trial. Lancet. 2016;387(10023):1057-65.</mixed-citation>
      </ref>
      <ref id="B175">
        <label>175</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bader</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Atallah</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Brennan</surname>
              <given-names>LF</given-names>
            </name>
            <name>
              <surname>Rimawi</surname>
              <given-names>RH</given-names>
            </name>
            <name>
              <surname>Khalil</surname>
              <given-names>ME</given-names>
            </name>
          </person-group>
          <article-title>Heart failure in the elderly: ten peculiar management considerations</article-title>
          <source>Heart Fail Rev</source>
          <year>2017</year>
          <volume>22</volume>
          <issue>2</issue>
          <fpage>219</fpage>
          <lpage>228</lpage>
        </element-citation>
        <mixed-citation>175. Bader F, Atallah B, Brennan LF, Rimawi RH, Khalil ME. Heart failure in the elderly: ten peculiar management considerations. Heart Fail Rev. 2017;22(2):219-28.</mixed-citation>
      </ref>
      <ref id="B176">
        <label>176</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ponikowski</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Voors</surname>
              <given-names>AA</given-names>
            </name>
            <name>
              <surname>Anker</surname>
              <given-names>SD</given-names>
            </name>
            <name>
              <surname>Bueno</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Cleland</surname>
              <given-names>JG</given-names>
            </name>
            <name>
              <surname>Coats</surname>
              <given-names>AS</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>ESC Scientific Document Group. 2016. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC</article-title>
          <source>Eur Heart J</source>
          <year>2016</year>
          <volume>37</volume>
          <issue>27</issue>
          <fpage>2129</fpage>
          <lpage>2200</lpage>
        </element-citation>
        <mixed-citation>176. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AS et al.; ESC Scientific Document Group. 2016. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37(27):2129-200.</mixed-citation>
      </ref>
      <ref id="B177">
        <label>177</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Yancy</surname>
              <given-names>CW</given-names>
            </name>
            <name>
              <surname>Jessup</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Bozkurt</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Butler</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Casey</surname>
              <given-names>DE</given-names>
              <suffix>Jr</suffix>
            </name>
            <name>
              <surname>Drazner</surname>
              <given-names>MH</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines</article-title>
          <source>Circulation</source>
          <year>2013</year>
          <volume>128</volume>
          <issue>16</issue>
          <fpage>e240</fpage>
          <lpage>e327</lpage>
        </element-citation>
        <mixed-citation>177. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH et al.; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;128(16):e240-327.</mixed-citation>
      </ref>
      <ref id="B178">
        <label>178</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Rickenbacher</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Kaufmann</surname>
              <given-names>BA</given-names>
            </name>
            <name>
              <surname>Maeder</surname>
              <given-names>MT</given-names>
            </name>
            <name>
              <surname>Bernheim</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Goetschalckx</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Pfister</surname>
              <given-names>O</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>TIMI-CHF Investigators. Heart failure with mid-range ejection fraction: a distinct clinical entity? Insights from the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIMI-CHF)</article-title>
          <source>Eur J Heart Fail</source>
          <year>2017</year>
          <volume>19</volume>
          <issue>12</issue>
          <fpage>1586</fpage>
          <lpage>1596</lpage>
        </element-citation>
        <mixed-citation>178. Rickenbacher P, Kaufmann BA, Maeder MT, Bernheim A, Goetschalckx K, Pfister O et al.; TIMI-CHF Investigators. Heart failure with mid-range ejection fraction: a distinct clinical entity? Insights from the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIMI-CHF). Eur J Heart Fail. 2017;19(12):1586-96.</mixed-citation>
      </ref>
      <ref id="B179">
        <label>179</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bocchi</surname>
              <given-names>EA</given-names>
            </name>
            <name>
              <surname>Marcondes-Braga</surname>
              <given-names>FG</given-names>
            </name>
            <name>
              <surname>Bacal</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Ferraz</surname>
              <given-names>AS</given-names>
            </name>
            <name>
              <surname>Albuquerque</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Rodrigues Dde</surname>
              <given-names>A</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Updating of the Brazilian guideline for chronic heart failure &#8211; 2012</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2012</year>
          <volume>98</volume>
          <supplement>1 Suppl 1</supplement>
          <fpage>1</fpage>
          <lpage>33</lpage>
        </element-citation>
        <mixed-citation>179. Bocchi EA, Marcondes-Braga FG, Bacal F, Ferraz AS, Albuquerque D, Rodrigues Dde A et al. [Updating of the Brazilian guideline for chronic heart failure &#8211; 2012]. Arq Bras Cardiol. 2012;98(1 Suppl 1):1-33.</mixed-citation>
      </ref>
      <ref id="B180">
        <label>180</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Vetrano</surname>
              <given-names>DL</given-names>
            </name>
            <name>
              <surname>Lattanzio</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Martone</surname>
              <given-names>AM</given-names>
            </name>
            <name>
              <surname>Landi</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Brandi</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Topinkova</surname>
              <given-names>E</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Treating heart failure in older and oldest old patients</article-title>
          <source>Curr Pharm Des</source>
          <year>2015</year>
          <volume>21</volume>
          <issue>13</issue>
          <fpage>1659</fpage>
          <lpage>1664</lpage>
        </element-citation>
        <mixed-citation>180. Vetrano DL, Lattanzio F, Martone AM, Landi F, Brandi V, Topinkova E et al. Treating heart failure in older and oldest old patients. Curr Pharm Des. 2015;21(13):1659-64.</mixed-citation>
      </ref>
      <ref id="B181">
        <label>181</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Upadhya</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Taffet</surname>
              <given-names>GE</given-names>
            </name>
            <name>
              <surname>Cheng</surname>
              <given-names>CP</given-names>
            </name>
            <name>
              <surname>Kitzman</surname>
              <given-names>DW</given-names>
            </name>
          </person-group>
          <article-title>J Heart failure with preserved ejection fraction in the elderly: scope of the problem</article-title>
          <source>J Mol Cell Cardiol</source>
          <year>2015</year>
          <month>06</month>
          <volume>83</volume>
          <fpage>73</fpage>
          <lpage>87</lpage>
        </element-citation>
        <mixed-citation>181. Upadhya B, Taffet GE, Cheng CP, Kitzman DW. J Heart failure with preserved ejection fraction in the elderly: scope of the problem. J Mol Cell Cardiol. 2015 Jun;83:73-87.</mixed-citation>
      </ref>
      <ref id="B182">
        <label>182</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Krueger</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Botermann</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Schorr</surname>
              <given-names>SG</given-names>
            </name>
            <name>
              <surname>Griese-Mammen</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Laufs</surname>
              <given-names>U</given-names>
            </name>
            <name>
              <surname>Schulz</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
          <article-title>Age-related medication adherence in patients with chronic heart failure: a systematic literature review</article-title>
          <source>Int J Cardiol</source>
          <year>2015</year>
          <month>04</month>
          <day>01</day>
          <volume>184</volume>
          <fpage>728</fpage>
          <lpage>735</lpage>
        </element-citation>
        <mixed-citation>182. Krueger K, Botermann L, Schorr SG, Griese-Mammen N, Laufs U, Schulz M. Age-related medication adherence in patients with chronic heart failure: a systematic literature review. Int J Cardiol. 2015 Apr 1;184:728-35.</mixed-citation>
      </ref>
      <ref id="B183">
        <label>183</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Chen</surname>
              <given-names>YM</given-names>
            </name>
            <name>
              <surname>Li</surname>
              <given-names>Y</given-names>
            </name>
          </person-group>
          <article-title>Safety and efficacy of exercise training in elderly heart failure patients: a systematic review and meta-analysis</article-title>
          <source>Int J Clin Pract</source>
          <year>2013</year>
          <volume>67</volume>
          <issue>11</issue>
          <fpage>1192</fpage>
          <lpage>1198</lpage>
        </element-citation>
        <mixed-citation>183. Chen YM, Li Y. Safety and efficacy of exercise training in elderly heart failure patients: a systematic review and meta-analysis. Int J Clin Pract. 2013;67(11):1192-8.</mixed-citation>
      </ref>
      <ref id="B184">
        <label>184</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Chin</surname>
              <given-names>KL</given-names>
            </name>
            <name>
              <surname>Skiba</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Tonkin</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Reid</surname>
              <given-names>CM</given-names>
            </name>
            <name>
              <surname>Liew</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Krum</surname>
              <given-names>H</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>The treatment gap in patients with chronic systolic heart failure: a systematic review of evidence-based prescribing in practice</article-title>
          <source>Heart Fail Rev</source>
          <year>2016</year>
          <volume>21</volume>
          <issue>6</issue>
          <fpage>675</fpage>
          <lpage>697</lpage>
        </element-citation>
        <mixed-citation>184. Chin KL, Skiba M, Tonkin A, Reid CM, Liew D, Krum H et al. The treatment gap in patients with chronic systolic heart failure: a systematic review of evidence-based prescribing in practice. Heart Fail Rev. 2016;21(6):675-97.</mixed-citation>
      </ref>
      <ref id="B185">
        <label>185</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Anguita S&#225;nchez</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Jim&#233;nez-Navarro</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Crespo</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Alonso-Pulp&#243;n</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>de Teresa</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Castro-Beiras</surname>
              <given-names>A</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>OBELICA study researchers. Effect of a training program for primary care physicians on the optimization of beta-blocker treatment in elderly patients with heart failure</article-title>
          <source>Rev Esp Cardiol</source>
          <year>2010</year>
          <volume>63</volume>
          <issue>6</issue>
          <fpage>677</fpage>
          <lpage>685</lpage>
        </element-citation>
        <mixed-citation>185. Anguita S&#225;nchez M, Jim&#233;nez-Navarro M, Crespo M, Alonso-Pulp&#243;n L, de Teresa E, Castro-Beiras A et al.; OBELICA study researchers. Effect of a training program for primary care physicians on the optimization of beta-blocker treatment in elderly patients with heart failure. Rev Esp Cardiol. 2010;63(6):677-85.</mixed-citation>
      </ref>
      <ref id="B186">
        <label>186</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Flather</surname>
              <given-names>MD</given-names>
            </name>
            <name>
              <surname>Shibata</surname>
              <given-names>MC</given-names>
            </name>
            <name>
              <surname>Coats</surname>
              <given-names>AJ</given-names>
            </name>
            <name>
              <surname>van Veldhuisen</surname>
              <given-names>DJ</given-names>
            </name>
            <name>
              <surname>Parkhomenko</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Borbola</surname>
              <given-names>J</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>SENIORS Investigators. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS)</article-title>
          <source>Eur Heart J</source>
          <year>2005</year>
          <volume>26</volume>
          <issue>3</issue>
          <fpage>215</fpage>
          <lpage>225</lpage>
        </element-citation>
        <mixed-citation>186. Flather MD, Shibata MC, Coats AJ, Van Veldhuisen DJ, Parkhomenko A, Borbola J et al.; SENIORS Investigators. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J. 2005;26(3):215-25.</mixed-citation>
      </ref>
      <ref id="B187">
        <label>187</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Rossi</surname>
              <given-names>JS</given-names>
            </name>
            <name>
              <surname>Flaherty</surname>
              <given-names>JD</given-names>
            </name>
            <name>
              <surname>Fonarow</surname>
              <given-names>GC</given-names>
            </name>
            <name>
              <surname>Nunez</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Gattis Stough</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>Abraham</surname>
              <given-names>WT</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Influence of coronary artery disease and coronary revascularization status on outcomes in patients with acute heart failure syndromes: a report from OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure)</article-title>
          <source>Eur J Heart Fail</source>
          <year>2008</year>
          <volume>10</volume>
          <issue>12</issue>
          <fpage>1215</fpage>
          <lpage>1223</lpage>
        </element-citation>
        <mixed-citation>187. Rossi JS, Flaherty JD, Fonarow GC, Nunez E, Gattis Stough W, Abraham WT et al. Influence of coronary artery disease and coronary revascularization status on outcomes in patients with acute heart failure syndromes: a report from OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) Eur J Heart Fail. 2008;10(12):1215-23.</mixed-citation>
      </ref>
      <ref id="B188">
        <label>188</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Komajda</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Hanon</surname>
              <given-names>O</given-names>
            </name>
            <name>
              <surname>Hochadel</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Lopez-Sendon</surname>
              <given-names>JL</given-names>
            </name>
            <name>
              <surname>Follath</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Ponikowski</surname>
              <given-names>P</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Contemporary management of octogenarians hospitalized for heart failure in Europe: Euro Heart Failure Survey II</article-title>
          <source>Eur Heart J</source>
          <year>2009</year>
          <volume>30</volume>
          <issue>4</issue>
          <fpage>478</fpage>
          <lpage>486</lpage>
        </element-citation>
        <mixed-citation>188. Komajda M, Hanon O, Hochadel M, Lopez-Sendon JL, Follath F, Ponikowski P et al. Contemporary management of octogenarians hospitalized for heart failure in Europe: Euro Heart Failure Survey II. Eur Heart J. 2009;30(4):478-86.</mixed-citation>
      </ref>
      <ref id="B189">
        <label>189</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>McMurray</surname>
              <given-names>JJ</given-names>
            </name>
            <name>
              <surname>Packer</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Desai</surname>
              <given-names>AS</given-names>
            </name>
            <name>
              <surname>Gong</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Lefkowitz</surname>
              <given-names>MP</given-names>
            </name>
            <name>
              <surname>Rizkala</surname>
              <given-names>AR</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure</article-title>
          <source>N Engl J Med</source>
          <year>2014</year>
          <volume>371</volume>
          <issue>11</issue>
          <fpage>993</fpage>
          <lpage>1004</lpage>
        </element-citation>
        <mixed-citation>189. McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR et al.; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993-1004.</mixed-citation>
      </ref>
      <ref id="B190">
        <label>190</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Edelmann</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Musial-Bright</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Gelbrich</surname>
              <given-names>G</given-names>
            </name>
          </person-group>
          <article-title>CIBIS-ELD Investigators and Project Multicenter Trials in the Competence Network Heart Failure. Tolerability and Feasibility of Beta-Blocker Titration in HFpEF Versus HFrEF: Insights From the CIBIS-ELD Trial</article-title>
          <source>JACC Heart Fail</source>
          <year>2016</year>
          <volume>4</volume>
          <issue>2</issue>
          <fpage>140</fpage>
          <lpage>149</lpage>
        </element-citation>
        <mixed-citation>190. Edelmann F, Musial-Bright L, Gelbrich G; CIBIS-ELD Investigators and Project Multicenter Trials in the Competence Network Heart Failure. Tolerability and Feasibility of Beta-Blocker Titration in HFpEF Versus HFrEF: Insights From the CIBIS-ELD Trial. JACC Heart Fail. 2016;4(2):140-9.</mixed-citation>
      </ref>
      <ref id="B191">
        <label>191</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Taddei</surname>
              <given-names>CF</given-names>
            </name>
            <name>
              <surname>Ramos</surname>
              <given-names>LR</given-names>
            </name>
            <name>
              <surname>Moraes</surname>
              <given-names>JC</given-names>
            </name>
            <name>
              <surname>Wajngarten</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Libberman</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Santos</surname>
              <given-names>SC</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Multicenter study of elderly patients in outpatient clinics of cardiology and geriatric Brazilian institutions</article-title>
          <source>Arq Bras Cardiol</source>
          <year>1997</year>
          <volume>69</volume>
          <issue>5</issue>
          <fpage>327</fpage>
          <lpage>333</lpage>
        </element-citation>
        <mixed-citation>191. Taddei CF, Ramos LR, Moraes JC, Wajngarten M, Libberman A, Santos SC et al. Multicenter study of elderly patients in outpatient clinics of cardiology and geriatric Brazilian institutions. Arq Bras Cardiol. 1997;69(5):327-33.</mixed-citation>
      </ref>
      <ref id="B192">
        <label>192</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Strait</surname>
              <given-names>JB</given-names>
            </name>
            <name>
              <surname>Lakatta</surname>
              <given-names>EG</given-names>
            </name>
          </person-group>
          <article-title>Aging-associated cardiovascular changes and their relationship to heart failure</article-title>
          <source>Heart Fail Clin</source>
          <year>2012</year>
          <volume>8</volume>
          <issue>1</issue>
          <fpage>143</fpage>
          <lpage>164</lpage>
        </element-citation>
        <mixed-citation>192. Strait JB, Lakatta EG. Aging-associated cardiovascular changes and their relationship to heart failure. Heart Fail Clin. 2012;8(1):143-64.</mixed-citation>
      </ref>
      <ref id="B193">
        <label>193</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Malachias</surname>
              <given-names>MV</given-names>
            </name>
            <name>
              <surname>P&#243;voa</surname>
              <given-names>RM</given-names>
            </name>
            <name>
              <surname>Nogueira</surname>
              <given-names>AR</given-names>
            </name>
            <name>
              <surname>Souza</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Costa</surname>
              <given-names>LS</given-names>
            </name>
            <name>
              <surname>Magalh&#227;es</surname>
              <given-names>ME</given-names>
            </name>
          </person-group>
          <article-title>Sociedade Brasileira de Cardiologia. 7a Diretriz Brasileira de hipertens&#227;o arterial</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2016</year>
          <volume>107</volume>
          <supplement>3 supl 3</supplement>
          <fpage>1</fpage>
          <lpage>83</lpage>
        </element-citation>
        <mixed-citation>193. Malachias MV, P&#243;voa RM, Nogueira AR, Souza D, Costa LS, Magalh&#227;es ME; Sociedade Brasileira de Cardiologia. 7a Diretriz Brasileira de hipertens&#227;o arterial. Arq Bras Cardiol. 2016;107(3 supl 3):1-83.</mixed-citation>
      </ref>
      <ref id="B194">
        <label>194</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Beckett</surname>
              <given-names>NS</given-names>
            </name>
            <name>
              <surname>Peters</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Fletcher</surname>
              <given-names>AE</given-names>
            </name>
            <name>
              <surname>Staessen</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Liu</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Dumitrascu</surname>
              <given-names>D</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>HYVET Study Group. Treatment of hypertension in patients 80 years of age or older</article-title>
          <source>N Engl J Med</source>
          <year>2008</year>
          <volume>358</volume>
          <issue>18</issue>
          <fpage>1887</fpage>
          <lpage>1898</lpage>
        </element-citation>
        <mixed-citation>194. Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D et al.; HYVET Study Group. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358(18):1887-98.</mixed-citation>
      </ref>
      <ref id="B195">
        <label>195</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Mancia</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Fagard</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Narkiewicz</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Redon</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Zanchetti</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>B&#246;hm</surname>
              <given-names>M</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)</article-title>
          <source>Eur Heart J</source>
          <year>2013</year>
          <volume>34</volume>
          <issue>28</issue>
          <fpage>2159</fpage>
          <lpage>2219</lpage>
        </element-citation>
        <mixed-citation>195. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, B&#246;hm M et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34(28):2159-219.</mixed-citation>
      </ref>
      <ref id="B196">
        <label>196</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Whelton</surname>
              <given-names>PK</given-names>
            </name>
            <name>
              <surname>Carey</surname>
              <given-names>RM</given-names>
            </name>
            <name>
              <surname>Aronow</surname>
              <given-names>WS</given-names>
            </name>
            <name>
              <surname>Casey</surname>
              <given-names>DE</given-names>
              <suffix>Jr</suffix>
            </name>
            <name>
              <surname>Collins</surname>
              <given-names>KJ</given-names>
            </name>
            <name>
              <surname>Dennison Himmelfarb</surname>
              <given-names>C</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2018</year>
          <volume>71</volume>
          <issue>19</issue>
          <fpage>e127</fpage>
          <lpage>e248</lpage>
        </element-citation>
        <mixed-citation>196. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018;71(19):e127-248.</mixed-citation>
      </ref>
      <ref id="B197">
        <label>197</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Desai</surname>
              <given-names>MY</given-names>
            </name>
            <name>
              <surname>Gerstenblith</surname>
              <given-names>G</given-names>
            </name>
          </person-group>
          <source>Contemporary cardiology: cardiovascular disease in the elderly</source>
          <publisher-loc>New Jersey</publisher-loc>
          <publisher-name>Humana Press</publisher-name>
          <year>2010</year>
          <fpage>247</fpage>
          <lpage>250</lpage>
        </element-citation>
        <mixed-citation>197. Desai MY, Gerstenblith G. Contemporary cardiology: cardiovascular disease in the elderly. New Jersey: Humana Press; 2010. p. 247-50.</mixed-citation>
      </ref>
      <ref id="B198">
        <label>198</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Harris</surname>
              <given-names>R</given-names>
            </name>
          </person-group>
          <source>Clinical geriatric cardiology</source>
          <edition>2nd. ed.</edition>
          <publisher-loc>Philadelphia</publisher-loc>
          <publisher-name>JB Lippincott Company</publisher-name>
          <year>1970</year>
        </element-citation>
        <mixed-citation>198. Harris R. Clinical geriatric cardiology. 2nd ed. Philadelphia: JB Lippincott Company; 1970.</mixed-citation>
      </ref>
      <ref id="B199">
        <label>199</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Cheitlin</surname>
              <given-names>MD</given-names>
            </name>
          </person-group>
          <chapter-title>Valve disease in octogenarian</chapter-title>
          <person-group person-group-type="editor">
            <name>
              <surname>Wenger</surname>
              <given-names>NK</given-names>
            </name>
          </person-group>
          <source>Cardiovascular disease in the octogenarian and beyond</source>
          <publisher-loc>London</publisher-loc>
          <publisher-name>Martin Dunitz</publisher-name>
          <year>1999</year>
          <fpage>255</fpage>
          <lpage>266</lpage>
        </element-citation>
        <mixed-citation>199. Cheitlin MD. Valve disease in octogenarian. In: Wenger NK. (editor). Cardiovascular disease in the octogenarian and beyond. London: Martin Dunitz; 1999. p. 255-66.</mixed-citation>
      </ref>
      <ref id="B200">
        <label>200</label>
        <element-citation publication-type="webpage">
          <person-group person-group-type="author">
            <name>
              <surname>Sharma</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Maron</surname>
              <given-names>DJ</given-names>
            </name>
            <name>
              <surname>Figueiredo</surname>
              <given-names>VM</given-names>
            </name>
            <name>
              <surname>Pressman</surname>
              <given-names>GS</given-names>
            </name>
            <name>
              <surname>Talavera</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Selpazuk</surname>
              <given-names>L</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Mitral annular calcification</article-title>
          <date-in-citation content-type="access-date">2017 Jan 30</date-in-citation>
          <comment>Available from: <ext-link ext-link-type="uri" xlink:href="https://emedicine.medscape.com/article/1967024-overview">https://emedicine.medscape.com/article/1967024-overview</ext-link></comment>
        </element-citation>
        <mixed-citation>200. Sharma S, Maron DJ, Figueiredo VM, Pressman GS, Talavera F, Selpazuk L et al. Mitral annular calcification. [Internet]. [Cited in 2017 Jan 30]. Available from: <ext-link ext-link-type="uri" xlink:href="https://emedicine.medscape.com/article/1967024-overview">https://emedicine.medscape.com/article/1967024-overview</ext-link>.</mixed-citation>
      </ref>
      <ref id="B201">
        <label>201</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Meneghelo</surname>
              <given-names>ZM</given-names>
            </name>
          </person-group>
          <chapter-title>Doen&#231;a valvar no idoso</chapter-title>
          <person-group person-group-type="editor">
            <name>
              <surname>Borges</surname>
              <given-names>JL</given-names>
            </name>
          </person-group>
          <source>Manual de Cardiogeriatria</source>
          <publisher-loc>S&#227;o Paulo</publisher-loc>
          <publisher-name>Lemos Editorial</publisher-name>
          <year>2012</year>
          <fpage>138</fpage>
          <lpage>141</lpage>
        </element-citation>
        <mixed-citation>201. Meneghelo ZM. Doen&#231;a valvar no idoso. In: Borges JL. ed. Manual de Cardiogeriatria. S&#227;o Paulo: Lemos Editorial; 2012. p. 138-41.</mixed-citation>
      </ref>
      <ref id="B202">
        <label>202</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Tarasoutchi</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Montera</surname>
              <given-names>MW</given-names>
            </name>
            <name>
              <surname>Grinberg</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Pi&#241;eiro</surname>
              <given-names>DJ</given-names>
            </name>
            <name>
              <surname>S&#225;nchez</surname>
              <given-names>CR</given-names>
            </name>
            <name>
              <surname>Bacelar</surname>
              <given-names>AC</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>[Brazilian Guidelines for Valve Disease &#8211; SBC 2011 / I Guideline Inter-American Valve Disease &#8211; 2011 SIAC]</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2011</year>
          <volume>97</volume>
          <supplement>5 Suppl 1</supplement>
          <fpage>1</fpage>
          <lpage>67</lpage>
        </element-citation>
        <mixed-citation>202. Tarasoutchi F, Montera MW, Grinberg M, Pi&#241;eiro DJ, S&#225;nchez CR, Bacelar AC et al; [Brazilian Guidelines for Valve Disease &#8211; SBC 2011 / I Guideline Inter-American Valve Disease &#8211; 2011 SIAC]. Arq Bras Cardiol. 2011;97(5 Suppl 1):1-67.</mixed-citation>
      </ref>
      <ref id="B203">
        <label>203</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Nishimiura</surname>
              <given-names>RA</given-names>
            </name>
            <name>
              <surname>Otto</surname>
              <given-names>CM</given-names>
            </name>
            <name>
              <surname>Bonow</surname>
              <given-names>RO</given-names>
            </name>
            <name>
              <surname>Carabello</surname>
              <given-names>BA</given-names>
            </name>
            <name>
              <surname>Erwin</surname>
              <given-names>JP</given-names>
              <suffix>3rd</suffix>
            </name>
            <name>
              <surname>Guyton</surname>
              <given-names>RA</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2014</year>
          <volume>63</volume>
          <issue>22</issue>
          <fpage>e57</fpage>
          <lpage>e185</lpage>
          <comment>Erratum in: J Am Coll Cardiol. 2014;63(22):2489</comment>
        </element-citation>
        <mixed-citation>203. Nishimiura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA et al.; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(22):e57-185. Erratum in: J Am Coll Cardiol. 2014;63(22):2489.</mixed-citation>
      </ref>
      <ref id="B204">
        <label>204</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Wann</surname>
              <given-names>LS</given-names>
            </name>
            <name>
              <surname>Curtis</surname>
              <given-names>AB</given-names>
            </name>
            <name>
              <surname>January</surname>
              <given-names>CT</given-names>
            </name>
            <name>
              <surname>Ellenbogen</surname>
              <given-names>KA</given-names>
            </name>
            <name>
              <surname>Lowe</surname>
              <given-names>JE</given-names>
            </name>
            <name>
              <surname>Estes</surname>
              <given-names>NA</given-names>
              <suffix>3rd</suffix>
            </name>
            <etal/>
          </person-group>
          <article-title>2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrilation (updating the 2006 guideline). A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2011</year>
          <volume>57</volume>
          <issue>2</issue>
          <fpage>223</fpage>
          <lpage>242</lpage>
        </element-citation>
        <mixed-citation>204. Wann LS, Curtis AB, January CT, Ellenbogen KA, Lowe JE, Estes NA 3rd et al. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrilation (updating the 2006 guideline). A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2011;57(2):223-42.</mixed-citation>
      </ref>
      <ref id="B205">
        <label>205</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Martins</surname>
              <given-names>RP</given-names>
            </name>
            <name>
              <surname>Galand</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Colette</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Behar</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Pavin</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Leclercq</surname>
              <given-names>C</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Defining nonvalvular atrial fibrillation: a quest for clarification</article-title>
          <source>Am Heart J</source>
          <year>2016</year>
          <month>08</month>
          <volume>178</volume>
          <fpage>161</fpage>
          <lpage>167</lpage>
        </element-citation>
        <mixed-citation>205. Martins RP, Galand V, Colette E, Behar N, Pavin D, Leclercq C et al. Defining nonvalvular atrial fibrillation: a quest for clarification. Am Heart J. 2016 Aug;178:161-7.</mixed-citation>
      </ref>
      <ref id="B206">
        <label>206</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Barbosa</surname>
              <given-names>PJ</given-names>
            </name>
            <name>
              <surname>M&#252;ller</surname>
              <given-names>RE</given-names>
            </name>
            <name>
              <surname>Latado</surname>
              <given-names>AL</given-names>
            </name>
            <name>
              <surname>Achutti</surname>
              <given-names>AC</given-names>
            </name>
            <name>
              <surname>Ramos</surname>
              <given-names>AI</given-names>
            </name>
            <name>
              <surname>Weksler</surname>
              <given-names>C</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Diretrizes Brasileiras para Diagn&#243;stico, Tratamento e Preven&#231;&#227;o da Febre Reum&#225;tica da Sociedade Brasileira de Cardiologia, da Sociedade Brasileira de Pediatria e da Sociedade Brasileira de Reumatologia</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2009</year>
          <volume>93</volume>
          <supplement>3 supl.4</supplement>
          <fpage>1</fpage>
          <lpage>18</lpage>
        </element-citation>
        <mixed-citation>206. Barbosa PJ, M&#252;ller RE, Latado AL, Achutti AC, Ramos AI, Weksler C et al. Diretrizes Brasileiras para Diagn&#243;stico, Tratamento e Preven&#231;&#227;o da Febre Reum&#225;tica da Sociedade Brasileira de Cardiologia, da Sociedade Brasileira de Pediatria e da Sociedade Brasileira de Reumatologia. Arq Bras Cardiol. 2009;93(3 supl.4):1-18.</mixed-citation>
      </ref>
      <ref id="B207">
        <label>207</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Habib</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Lancellotti</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Antunes</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Bongiorni</surname>
              <given-names>MG</given-names>
            </name>
            <name>
              <surname>Casalta</surname>
              <given-names>JP</given-names>
            </name>
            <name>
              <surname>Del Zotti</surname>
              <given-names>F</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>ESC Scientific Document Group. 2015 ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM)</article-title>
          <source>Eur Heart J</source>
          <year>2015</year>
          <volume>36</volume>
          <issue>44</issue>
          <fpage>3075</fpage>
          <lpage>3128</lpage>
        </element-citation>
        <mixed-citation>207. Habib G, Lancellotti P, Antunes MJ, Bongiorni MG, Casalta JP, Del Zotti F et al.; ESC Scientific Document Group. 2015 ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J. 2015;36(44):3075-128.</mixed-citation>
      </ref>
      <ref id="B208">
        <label>208</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Monmeneu Menadas</surname>
              <given-names>JV</given-names>
            </name>
            <name>
              <surname>Mar&#237;n Ortu&#241;o</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Reyes Gomis</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Jord&#225;n Torrent</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Garc&#237;a Mart&#237;nez</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Bod&#237; Peris</surname>
              <given-names>V</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Betablockade and exercise capacity in patients with mitral stenosis in sinus rhythm</article-title>
          <source>J Heart Valve Dis</source>
          <year>2002</year>
          <volume>11</volume>
          <issue>2</issue>
          <fpage>199</fpage>
          <lpage>203</lpage>
        </element-citation>
        <mixed-citation>208. Monmeneu Menadas JV, Mar&#237;n Ortu&#241;o F, Reyes Gomis F, Jord&#225;n Torrent A, Garc&#237;a Mart&#237;nez M, Bod&#237; Peris V et al. Betablockade and exercise capacity in patients with mitral stenosis in sinus rhythm. J Heart Valve Dis. 2002;11(2):199-203.</mixed-citation>
      </ref>
      <ref id="B209">
        <label>209</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Teresa</surname>
              <given-names>E</given-names>
            </name>
          </person-group>
          <article-title>Tratamiento diur&#233;tico de la insuficiencia card&#237;aca</article-title>
          <source>Rev Esp Cardiol Supl</source>
          <year>2007</year>
          <volume>7</volume>
          <fpage>34F</fpage>
          <lpage>44F</lpage>
        </element-citation>
        <mixed-citation>209. Teresa E. Tratamiento diur&#233;tico de la insuficiencia card&#237;aca. Rev Esp Cardiol Supl. 2007;7:34F-44F.</mixed-citation>
      </ref>
      <ref id="B210">
        <label>210</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bouleti</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Iung</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Laou&#233;nan</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Himbert</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Brochet</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Messika-Zeitoun</surname>
              <given-names>D</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Late results of percutaneous mitral commissurotomy up to 20 years development and validation of a risk score predicting late functional results from a series of 912 patients</article-title>
          <source>Circulation</source>
          <year>2012</year>
          <volume>125</volume>
          <issue>17</issue>
          <fpage>2119</fpage>
          <lpage>2127</lpage>
        </element-citation>
        <mixed-citation>210. Bouleti C, Iung B, Laou&#233;nan C, Himbert D, Brochet E, Messika-Zeitoun D et al. Late results of percutaneous mitral commissurotomy up to 20 years development and validation of a risk score predicting late functional results from a series of 912 patients. Circulation. 2012;125(17):2119-27.</mixed-citation>
      </ref>
      <ref id="B211">
        <label>211</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Wilkins</surname>
              <given-names>GT</given-names>
            </name>
            <name>
              <surname>Weyman</surname>
              <given-names>AE</given-names>
            </name>
            <name>
              <surname>Abascal</surname>
              <given-names>VM</given-names>
            </name>
            <name>
              <surname>Block</surname>
              <given-names>PC</given-names>
            </name>
            <name>
              <surname>Palacios</surname>
              <given-names>IF</given-names>
            </name>
          </person-group>
          <article-title>Percutaneous balloon dilatation of the mitral valve: an analysis of echocardiographic variables related to outcome and the mechanism of dilatation</article-title>
          <source>Br Heart J</source>
          <year>1988</year>
          <volume>60</volume>
          <issue>4</issue>
          <fpage>299</fpage>
          <lpage>308</lpage>
        </element-citation>
        <mixed-citation>211. Wilkins GT, Weyman AE, Abascal VM, Block PC, Palacios IF. Percutaneous balloon dilatation of the mitral valve: an analysis of echocardiographic variables related to outcome and the mechanism of dilatation. Br Heart J. 1988;60(4):299-308.</mixed-citation>
      </ref>
      <ref id="B212">
        <label>212</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Chmielak</surname>
              <given-names>Z</given-names>
            </name>
            <name>
              <surname>Klopotowski</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Demokow</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Konka</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Hoffman</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Kuku&#322;a</surname>
              <given-names>K</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Percutaneous mitral balloon valvuloplasty beyond 65 years of age</article-title>
          <source>Cardiol J</source>
          <year>2013</year>
          <volume>20</volume>
          <issue>1</issue>
          <fpage>44</fpage>
          <lpage>51</lpage>
        </element-citation>
        <mixed-citation>212. Chmielak Z, Klopotowski M, Demokow M, Konka M, Hoffman P, Kuku&#322;a K et al. Percutaneous mitral balloon valvuloplasty beyond 65 years of age. Cardiol J. 2013;20(1):44-51.</mixed-citation>
      </ref>
      <ref id="B213">
        <label>213</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Sud</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Agarwal</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Parashar</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Raza</surname>
              <given-names>MQ</given-names>
            </name>
            <name>
              <surname>Patel</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Min</surname>
              <given-names>D</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Degenerative mitral stenosis unmet need for percutaneous interventions</article-title>
          <source>Circulation</source>
          <year>2016</year>
          <volume>133</volume>
          <issue>16</issue>
          <fpage>1594</fpage>
          <lpage>1604</lpage>
        </element-citation>
        <mixed-citation>213. Sud K, Agarwal S, Parashar A, Raza MQ, Patel K, Min D et al. Degenerative mitral stenosis unmet need for percutaneous interventions. Circulation. 2016;133(16):1594-604.</mixed-citation>
      </ref>
      <ref id="B214">
        <label>214</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Guerrero</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Dvir</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Himbert</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Urena</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Eleid</surname>
              <given-names>M</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Transcatheter mitral valve replacement in native mitral valve disease with severe mitral annular calcification: results from the First Multicenter Global Registry</article-title>
          <source>JACC Cardiovasc Interv</source>
          <year>2016</year>
          <volume>9</volume>
          <issue>13</issue>
          <fpage>136</fpage>
          <lpage>171</lpage>
        </element-citation>
        <mixed-citation>214. Guerrero M, Dvir D, Himbert D, Urena M, Eleid M et al. Transcatheter mitral valve replacement in native mitral valve disease with severe mitral annular calcification: results from the First Multicenter Global Registry. JACC Cardiovasc Interv. 2016;9(13):136-71.</mixed-citation>
      </ref>
      <ref id="B215">
        <label>215</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Singh</surname>
              <given-names>JP</given-names>
            </name>
            <name>
              <surname>Evans</surname>
              <given-names>JC</given-names>
            </name>
            <name>
              <surname>Levy</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Larson</surname>
              <given-names>MG</given-names>
            </name>
            <name>
              <surname>Freed</surname>
              <given-names>LA</given-names>
            </name>
            <name>
              <surname>Fuller</surname>
              <given-names>DL</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Prevalence and clinical determinants of mitral, tricuspid and aortic regurgitation (The Framingham Heart Study)</article-title>
          <source>Am J Cardiol</source>
          <year>1999</year>
          <volume>83</volume>
          <issue>6</issue>
          <fpage>897</fpage>
          <lpage>902</lpage>
          <comment>Erratum in: Am J Cardiol. 1999;84(9):1143</comment>
        </element-citation>
        <mixed-citation>215. Singh JP, Evans JC, Levy D, Larson MG, Freed LA, Fuller DL et al. Prevalence and clinical determinants of mitral, tricuspid and aortic regurgitation (The Framingham Heart Study). Am J Cardiol. 1999;83(6):897-902. Erratum in: Am J Cardiol. 1999;84(9):1143.</mixed-citation>
      </ref>
      <ref id="B216">
        <label>216</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bell</surname>
              <given-names>MH</given-names>
            </name>
            <name>
              <surname>Mintz</surname>
              <given-names>GS</given-names>
            </name>
          </person-group>
          <article-title>Mitral valve disease in the elderly</article-title>
          <source>Cardiovasc Clin</source>
          <year>1986</year>
          <volume>16</volume>
          <issue>2</issue>
          <fpage>313</fpage>
          <lpage>324</lpage>
        </element-citation>
        <mixed-citation>216. Bell MH, Mintz GS. Mitral valve disease in the elderly. Cardiovasc Clin. 1986;16(2):313-24.</mixed-citation>
      </ref>
      <ref id="B217">
        <label>217</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Huep</surname>
              <given-names>JC</given-names>
            </name>
            <name>
              <surname>Gon&#231;alves</surname>
              <given-names>RS</given-names>
            </name>
            <name>
              <surname>Ferreira</surname>
              <given-names>RM</given-names>
            </name>
          </person-group>
          <article-title>A import&#226;ncia do eletrocardiograma, da radiografia de t&#243;rax e dos testes de capacidade funcional na avalia&#231;&#227;o das valvopatias mitrais</article-title>
          <source>Rev Soc Cardiol Estado S&#227;o Paulo</source>
          <year>2008</year>
          <volume>18</volume>
          <issue>4</issue>
          <fpage>319</fpage>
          <lpage>327</lpage>
        </element-citation>
        <mixed-citation>217. Huep JC, Gon&#231;alves RS, Ferreira RM. A import&#226;ncia do eletrocardiograma, da radiografia de t&#243;rax e dos testes de capacidade funcional na avalia&#231;&#227;o das valvopatias mitrais. Rev Soc Cardiol Estado S&#227;o Paulo. 2008;18(4):319-27.</mixed-citation>
      </ref>
      <ref id="B218">
        <label>218</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Rossi</surname>
              <given-names>EG</given-names>
            </name>
          </person-group>
          <chapter-title>Insufici&#234;ncia mitral</chapter-title>
          <person-group person-group-type="editor">
            <name>
              <surname>Grinberg</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Sampaio</surname>
              <given-names>RO</given-names>
            </name>
          </person-group>
          <source>Doen&#231;a Valvar</source>
          <publisher-loc>S&#227;o Paulo</publisher-loc>
          <publisher-name>Manole</publisher-name>
          <year>2006</year>
        </element-citation>
        <mixed-citation>218. Rossi EG. Insufici&#234;ncia mitral. In: Grinberg M, Sampaio RO. Doen&#231;a Valvar. S&#227;o Paulo: Manole; 2006.</mixed-citation>
      </ref>
      <ref id="B219">
        <label>219</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Moffa</surname>
              <given-names>PJ</given-names>
            </name>
            <name>
              <surname>Sanches</surname>
              <given-names>PCR</given-names>
            </name>
            <name>
              <surname>Uchida</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
          <chapter-title>Eletrocardiologia: utilidade do eletrocardiograma em repouso</chapter-title>
          <person-group person-group-type="editor">
            <name>
              <surname>Grinberg</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Sampaio</surname>
              <given-names>RO</given-names>
            </name>
          </person-group>
          <source>Doen&#231;a Valvar</source>
          <publisher-loc>S&#227;o Paulo</publisher-loc>
          <publisher-name>Manole</publisher-name>
          <year>2006</year>
        </element-citation>
        <mixed-citation>219. Moffa PJ, Sanches PCR, Uchida A. Eletrocardiologia: utilidade do eletrocardiograma em repouso. In: Grinberg M, Sampaio RO. Doen&#231;a Valvar. S&#227;o Paulo: Manole; 2006.</mixed-citation>
      </ref>
      <ref id="B220">
        <label>220</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Lucarelli</surname>
              <given-names>C</given-names>
            </name>
          </person-group>
          <chapter-title>Radiologia convencional</chapter-title>
          <person-group person-group-type="editor">
            <name>
              <surname>Grimberg</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Sampaio</surname>
              <given-names>RO</given-names>
            </name>
          </person-group>
          <source>Doen&#231;a Valvar</source>
          <publisher-loc>S&#227;o Paulo</publisher-loc>
          <publisher-name>Manole</publisher-name>
          <year>2006</year>
        </element-citation>
        <mixed-citation>220. Lucarelli C. Radiologia convencional. In: Grimberg M, Sampaio RO. Doen&#231;a Valvar. S&#227;o Paulo: Manole; 2006.</mixed-citation>
      </ref>
      <ref id="B221">
        <label>221</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Vahanian</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Alfieri</surname>
              <given-names>O</given-names>
            </name>
            <name>
              <surname>Andreotti</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Antunes</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Bar&#243;n-Esquivias</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Baumgartner</surname>
              <given-names>H</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC); European Association for Cardio-Thoracic Surgery (EACTS). Guidelines on the management of valvular heart disease (version 2012)</article-title>
          <source>Eur Heart J</source>
          <year>2012</year>
          <volume>33</volume>
          <issue>19</issue>
          <fpage>2451</fpage>
          <lpage>2496</lpage>
        </element-citation>
        <mixed-citation>221. Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Bar&#243;n-Esquivias G, Baumgartner H et al.; Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC); European Association for Cardio-Thoracic Surgery (EACTS). Guidelines on the management of valvular heart disease (version 2012). Eur Heart J. 2012;33(19):2451-96.</mixed-citation>
      </ref>
      <ref id="B222">
        <label>222</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Nishimura</surname>
              <given-names>RA</given-names>
            </name>
            <name>
              <surname>Otto</surname>
              <given-names>CM</given-names>
            </name>
            <name>
              <surname>Bonow</surname>
              <given-names>RO</given-names>
            </name>
            <name>
              <surname>Carabello</surname>
              <given-names>BA</given-names>
            </name>
            <name>
              <surname>Erwin</surname>
              <given-names>JP</given-names>
              <suffix>3rd</suffix>
            </name>
            <name>
              <surname>Guyton</surname>
              <given-names>RA</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>ACC/AHA Task Force Members. 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines</article-title>
          <source>Circulation</source>
          <year>2014</year>
          <volume>129</volume>
          <issue>23</issue>
          <fpage>e521</fpage>
          <lpage>e643</lpage>
          <comment>Erratum in: Circulation. 2014;130(13):e120. Circulation. 2014;129(23):e651</comment>
        </element-citation>
        <mixed-citation>222. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA et al.; ACC/AHA Task Force Members. 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(23):e521-643. Erratum in: Circulation. 2014;130(13):e120. Circulation. 2014;129(23):e651.</mixed-citation>
      </ref>
      <ref id="B223">
        <label>223</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bonow</surname>
              <given-names>RO</given-names>
            </name>
            <name>
              <surname>Carabello</surname>
              <given-names>BA</given-names>
            </name>
            <name>
              <surname>Chatterjee</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>de Leon</surname>
              <given-names>AC</given-names>
              <suffix>Jr</suffix>
            </name>
            <name>
              <surname>Faxon</surname>
              <given-names>DP</given-names>
            </name>
            <name>
              <surname>Freed</surname>
              <given-names>MD</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>American College of Cardiology; American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the management of patients with valvular heart disease); Society of Cardiovascular Anesthesiologists. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing Committee to Revise the 1998 guidelines for the management of patients with valvular heart disease) developed in collaboration with the Society of Cardiovascular Anesthesiologists endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2006</year>
          <volume>48</volume>
          <issue>3</issue>
          <fpage>e1</fpage>
          <lpage>e148</lpage>
          <comment>Erratum in: J Am Coll Cardiol. 2007;49(9):1014</comment>
        </element-citation>
        <mixed-citation>223. Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr, Faxon DP, Freed MD et al.; American College of Cardiology; American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the management of patients with valvular heart disease); Society of Cardiovascular Anesthesiologists. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing Committee to Revise the 1998 guidelines for the management of patients with valvular heart disease) developed in collaboration with the Society of Cardiovascular Anesthesiologists endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. J Am Coll Cardiol. 2006;48(3):e1-148. Erratum in: J Am Coll Cardiol. 2007;49(9):1014.</mixed-citation>
      </ref>
      <ref id="B224">
        <label>224</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Borer</surname>
              <given-names>JS</given-names>
            </name>
            <name>
              <surname>Bonow</surname>
              <given-names>RO</given-names>
            </name>
          </person-group>
          <article-title>Contemporary approach to aortic and mitral regurgitation</article-title>
          <source>Circulation</source>
          <year>2003</year>
          <volume>108</volume>
          <issue>20</issue>
          <fpage>2432</fpage>
          <lpage>2438</lpage>
        </element-citation>
        <mixed-citation>224. Borer JS, Bonow RO. Contemporary approach to aortic and mitral regurgitation. Circulation. 2003;108(20):2432-8.</mixed-citation>
      </ref>
      <ref id="B225">
        <label>225</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Sampaio</surname>
              <given-names>RO</given-names>
            </name>
            <name>
              <surname>Grinberg</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Leite</surname>
              <given-names>JJ</given-names>
            </name>
            <name>
              <surname>Tarasoutchi</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Chalela</surname>
              <given-names>WA</given-names>
            </name>
            <name>
              <surname>Izaki</surname>
              <given-names>M</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Effect of enalapril on left ventricular diameters and exercise capacity in asymptomatic or mildly symptomatic patients with regurgitation secondary to mitral valve prolapse or rheumatic heart disease</article-title>
          <source>Am J Cardiol</source>
          <year>2005</year>
          <volume>96</volume>
          <issue>1</issue>
          <fpage>117</fpage>
          <lpage>121</lpage>
        </element-citation>
        <mixed-citation>225. Sampaio RO, Grinberg M, Leite JJ, Tarasoutchi F, Chalela WA, Izaki M et al. Effect of enalapril on left ventricular diameters and exercise capacity in asymptomatic or mildly symptomatic patients with regurgitation secondary to mitral valve prolapse or rheumatic heart disease. Am J Cardiol. 2005;96(1):117-21.</mixed-citation>
      </ref>
      <ref id="B226">
        <label>226</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Reuter</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Garrigue</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Barold</surname>
              <given-names>SS</given-names>
            </name>
            <name>
              <surname>Jais</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Hocini</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Haissaguerre</surname>
              <given-names>M</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Comparison of characteristics in responders versus nonresponders with biventricular pacing for drug-resistant congestive heart failure</article-title>
          <source>Am J Cardiol</source>
          <year>2002</year>
          <volume>89</volume>
          <issue>3</issue>
          <fpage>346</fpage>
          <lpage>350</lpage>
        </element-citation>
        <mixed-citation>226. Reuter S, Garrigue S, Barold SS, Jais P, Hocini M, Haissaguerre M et al. Comparison of characteristics in responders versus nonresponders with biventricular pacing for drug-resistant congestive heart failure. Am J Cardiol. 2002;89(3):346-50.</mixed-citation>
      </ref>
      <ref id="B227">
        <label>227</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Lazam</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Vanoverschelde</surname>
              <given-names>JL</given-names>
            </name>
            <name>
              <surname>Tribouilloy</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Grigioni</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Suri</surname>
              <given-names>RM</given-names>
            </name>
            <name>
              <surname>Avierinos</surname>
              <given-names>JF</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>MIDA (Mitral Regurgitation International Database) Investigators. Twenty-year outcome after mitral repair versus replacement for severe degenerative mitral regurgitation: analysis of a large, prospective, multicenter, international registry</article-title>
          <source>Circulation</source>
          <year>2017</year>
          <volume>135</volume>
          <issue>5</issue>
          <fpage>410</fpage>
          <lpage>422</lpage>
        </element-citation>
        <mixed-citation>227. Lazam S, Vanoverschelde JL, Tribouilloy C, Grigioni F, Suri RM, Avierinos JF et al.; MIDA (Mitral Regurgitation International Database) Investigators. Twenty-year outcome after mitral repair versus replacement for severe degenerative mitral regurgitation: analysis of a large, prospective, multicenter, international registry. Circulation. 2017;135(5):410-22.</mixed-citation>
      </ref>
      <ref id="B228">
        <label>228</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Prendergast</surname>
              <given-names>BD</given-names>
            </name>
            <name>
              <surname>De Bonis</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
          <article-title>Valve repair: a durable surgical option in degenerative mitral regurgitation</article-title>
          <source>Circulation</source>
          <year>2017</year>
          <volume>135</volume>
          <issue>5</issue>
          <fpage>423</fpage>
          <lpage>425</lpage>
        </element-citation>
        <mixed-citation>228. Prendergast BD, De Bonis M. Valve repair: a durable surgical option in degenerative mitral regurgitation. Circulation. 2017;135(5):423-5.</mixed-citation>
      </ref>
      <ref id="B229">
        <label>229</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Muller</surname>
              <given-names>DW</given-names>
            </name>
            <name>
              <surname>Farivar</surname>
              <given-names>RS</given-names>
            </name>
            <name>
              <surname>Jansz</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Bae</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Walters</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Clarke</surname>
              <given-names>A</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Tendyne Global Feasibility Trial Investigators. Transcatheter mitral valve replacement for patients with symptomatic mitral regurgitation</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2017</year>
          <volume>69</volume>
          <issue>4</issue>
          <fpage>381</fpage>
          <lpage>391</lpage>
        </element-citation>
        <mixed-citation>229. Muller DW, Farivar RS, Jansz P, Bae R, Walters D, Clarke A et al.; Tendyne Global Feasibility Trial Investigators. Transcatheter mitral valve replacement for patients with symptomatic mitral regurgitation. J Am Coll Cardiol. 2017;69(4):381-91.</mixed-citation>
      </ref>
      <ref id="B230">
        <label>230</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Edwards</surname>
              <given-names>FH</given-names>
            </name>
            <name>
              <surname>Cohen</surname>
              <given-names>DJ</given-names>
            </name>
            <name>
              <surname>O'Brien</surname>
              <given-names>SM</given-names>
            </name>
            <name>
              <surname>Peterson</surname>
              <given-names>ED</given-names>
            </name>
            <name>
              <surname>Mack</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Shahian</surname>
              <given-names>DM</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Steering Committee of the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Development and validation of a risk prediction model for in-hospital mortality after transcatheter aortic valve replacement</article-title>
          <source>JAMA Cardiol</source>
          <year>2016</year>
          <volume>1</volume>
          <issue>1</issue>
          <fpage>46</fpage>
          <lpage>52</lpage>
        </element-citation>
        <mixed-citation>230. Edwards FH, Cohen DJ, O'Brien SM, Peterson ED, Mack MJ, Shahian DM et al.; Steering Committee of the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Development and validation of a risk prediction model for in-hospital mortality after transcatheter aortic valve replacement. JAMA Cardiol. 2016;1(1):46-52.</mixed-citation>
      </ref>
      <ref id="B231">
        <label>231</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Rolfson</surname>
              <given-names>DB</given-names>
            </name>
            <name>
              <surname>Majumdar</surname>
              <given-names>SR</given-names>
            </name>
            <name>
              <surname>Tsuyuki</surname>
              <given-names>RT</given-names>
            </name>
            <name>
              <surname>Tahir</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Rockwood</surname>
              <given-names>K</given-names>
            </name>
          </person-group>
          <article-title>Validity and reliability of the Edmonton Frail Scale</article-title>
          <source>Age Ageing</source>
          <year>2006</year>
          <volume>35</volume>
          <issue>5</issue>
          <fpage>526</fpage>
          <lpage>529</lpage>
        </element-citation>
        <mixed-citation>231. Rolfson DB, Majumdar SR, Tsuyuki RT, Tahir A, Rockwood K. Validity and reliability of the Edmonton Frail Scale. Age Ageing. 2006;35(5):526-9.</mixed-citation>
      </ref>
      <ref id="B232">
        <label>232</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Enriquez-Sarano</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Tajik</surname>
              <given-names>AJ</given-names>
            </name>
          </person-group>
          <article-title>Clinical practice: aortic regurgitation</article-title>
          <source>N Engl J Med</source>
          <year>2004</year>
          <volume>351</volume>
          <issue>15</issue>
          <fpage>1539</fpage>
          <lpage>1546</lpage>
        </element-citation>
        <mixed-citation>232. Enriquez-Sarano M, Tajik AJ. Clinical practice: aortic regurgitation. N Engl J Med. 2004;351(15):1539-46.</mixed-citation>
      </ref>
      <ref id="B233">
        <label>233</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Gaasch</surname>
              <given-names>WH</given-names>
            </name>
            <name>
              <surname>Sundaram</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Meyer</surname>
              <given-names>TE</given-names>
            </name>
          </person-group>
          <article-title>Managing asymptomatic patients with chronic aortic regurgitation</article-title>
          <source>Chest</source>
          <year>1997</year>
          <volume>111</volume>
          <issue>6</issue>
          <fpage>1702</fpage>
          <lpage>1709</lpage>
        </element-citation>
        <mixed-citation>233. Gaasch WH, Sundaram M, Meyer TE. Managing asymptomatic patients with chronic aortic regurgitation. Chest. 1997;111(6):1702-9.</mixed-citation>
      </ref>
      <ref id="B234">
        <label>234</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bonow</surname>
              <given-names>RO</given-names>
            </name>
            <name>
              <surname>Lakatos</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Maron</surname>
              <given-names>BJ</given-names>
            </name>
            <name>
              <surname>Epstein</surname>
              <given-names>SE</given-names>
            </name>
          </person-group>
          <article-title>Serial long-term assessment of the natural history of asymptomatic patients with chronic aortic regurgitation and normal left ventricular systolic function</article-title>
          <source>Circulation</source>
          <year>1991</year>
          <volume>84</volume>
          <issue>4</issue>
          <fpage>1625</fpage>
          <lpage>1635</lpage>
        </element-citation>
        <mixed-citation>234. Bonow RO, Lakatos E, Maron BJ, Epstein SE. Serial long-term assessment of the natural history of asymptomatic patients with chronic aortic regurgitation and normal left ventricular systolic function. Circulation. 1991;84(4):1625-35.</mixed-citation>
      </ref>
      <ref id="B235">
        <label>235</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Lancelotti</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Rosenhek</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Pibarot</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Iung</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Otto</surname>
              <given-names>CM</given-names>
            </name>
            <name>
              <surname>Tornos</surname>
              <given-names>P</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>ESC Working Group on Valvular Heart Disease position paper--heart valve clinics: organization, structure, and experiences</article-title>
          <source>Eur Heart J</source>
          <year>2013</year>
          <volume>34</volume>
          <issue>21</issue>
          <fpage>1597</fpage>
          <lpage>1606</lpage>
        </element-citation>
        <mixed-citation>235. Lancelotti P, Rosenhek R, Pibarot P, Iung B, Otto CM, Tornos P et al. ESC Working Group on Valvular Heart Disease position paper--heart valve clinics: organization, structure, and experiences. Eur Heart J. 2013;34(21):1597-606.</mixed-citation>
      </ref>
      <ref id="B236">
        <label>236</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Evangelista</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Tornos</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Sambola</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Permanyer-Miralda</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Soler-Soler</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Long-term vasodilator therapy in patients with severe aortic regurgitation</article-title>
          <source>N Engl J Med</source>
          <year>2005</year>
          <volume>353</volume>
          <issue>13</issue>
          <fpage>1342</fpage>
          <lpage>1349</lpage>
        </element-citation>
        <mixed-citation>236. Evangelista A, Tornos P, Sambola A, Permanyer-Miralda G, Soler-Soler J. Long-term vasodilator therapy in patients with severe aortic regurgitation. N Engl J Med. 2005;353(13):1342-9.</mixed-citation>
      </ref>
      <ref id="B237">
        <label>237</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>de Meester</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Pasquet</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Gerber</surname>
              <given-names>BL</given-names>
            </name>
            <name>
              <surname>Vancraeynest</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Noirhomme</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>El Khoury</surname>
              <given-names>G</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Valve repair improves the outcome of surgery for chronic severe aortic regurgitation: a propensity score analysis</article-title>
          <source>J Thorac Cardiovasc Surg</source>
          <year>2014</year>
          <volume>148</volume>
          <issue>5</issue>
          <fpage>1913</fpage>
          <lpage>1920</lpage>
        </element-citation>
        <mixed-citation>237. de Meester C, Pasquet A, Gerber BL, Vancraeynest D, Noirhomme P, El Khoury G et al. Valve repair improves the outcome of surgery for chronic severe aortic regurgitation: a propensity score analysis. J Thorac Cardiovasc Surg. 2014;148(5):1913-20.</mixed-citation>
      </ref>
      <ref id="B238">
        <label>238</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Testa</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Latib</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Rossi</surname>
              <given-names>ML</given-names>
            </name>
            <name>
              <surname>de Marco</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>de Carlo</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Fiorina</surname>
              <given-names>C</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>CoreValve implantation for severe aortic regurgitation: a multicentre registry</article-title>
          <source>EuroIntervention</source>
          <year>2014</year>
          <volume>10</volume>
          <issue>6</issue>
          <fpage>739</fpage>
          <lpage>745</lpage>
        </element-citation>
        <mixed-citation>238. Testa L, Latib A, Rossi ML, De Marco F, De Carlo M, Fiorina C et al. CoreValve implantation for severe aortic regurgitation: a multicentre registry. EuroIntervention. 2014;10(6):739-45.</mixed-citation>
      </ref>
      <ref id="B239">
        <label>239</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Hogevik</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Olaison</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Anderson</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Lindberg</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Alestig</surname>
              <given-names>K</given-names>
            </name>
          </person-group>
          <article-title>Epidemiologic aspects of infective endocarditis in an urban population. A 5-years prospective study</article-title>
          <source>Medicine (Baltimore)</source>
          <year>1995</year>
          <volume>74</volume>
          <issue>6</issue>
          <fpage>324</fpage>
          <lpage>339</lpage>
        </element-citation>
        <mixed-citation>239. Hogevik H, Olaison L, Anderson R, Lindberg J, Alestig K. Epidemiologic aspects of infective endocarditis in an urban population. A 5-years prospective study. Medicine (Baltimore). 1995;74(6):324-39.</mixed-citation>
      </ref>
      <ref id="B240">
        <label>240</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Terpenning</surname>
              <given-names>MS</given-names>
            </name>
            <name>
              <surname>Buggy</surname>
              <given-names>BP</given-names>
            </name>
            <name>
              <surname>Kauffman</surname>
              <given-names>CA</given-names>
            </name>
          </person-group>
          <article-title>Infective endocarditis: clinical features in young and elderly patients</article-title>
          <source>Am J Med</source>
          <year>1987</year>
          <volume>83</volume>
          <issue>4</issue>
          <fpage>626</fpage>
          <lpage>634</lpage>
        </element-citation>
        <mixed-citation>240. Terpenning MS, Buggy BP, Kauffman CA. Infective endocarditis: clinical features in young and elderly patients. Am J Med. 1987;83(4):626-34.</mixed-citation>
      </ref>
      <ref id="B241">
        <label>241</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Selton-suty</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Hoen</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Grentzinger</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Houplon</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Maignan</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Juilli&#232;re</surname>
              <given-names>Y</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Clinical and bacteriological characteristics of endocarditis in the elderly</article-title>
          <source>Heart</source>
          <year>1997</year>
          <volume>77</volume>
          <issue>3</issue>
          <fpage>260</fpage>
          <lpage>263</lpage>
        </element-citation>
        <mixed-citation>241. Selton-suty C, Hoen B, GrentzingerA, Houplon P, Maignan M, Juilli&#232;re Y et al. Clinical and bacteriological characteristics of endocarditis in the elderly. Heart. 1997;77(3):260-3.</mixed-citation>
      </ref>
      <ref id="B242">
        <label>242</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Stewart</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Silimperi</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Harris</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Wise</surname>
              <given-names>NK</given-names>
            </name>
            <name>
              <surname>Fraker</surname>
              <given-names>TD</given-names>
              <suffix>Jr</suffix>
            </name>
            <name>
              <surname>Kisslo</surname>
              <given-names>JA</given-names>
            </name>
          </person-group>
          <article-title>Echocardiographic documentation of vegetative lesions in infective endocarditis: clinical implications</article-title>
          <source>Circulation</source>
          <year>1980</year>
          <volume>61</volume>
          <issue>2</issue>
          <fpage>374</fpage>
          <lpage>380</lpage>
        </element-citation>
        <mixed-citation>242. Stewart JA, Silimperi D, Harris P, Wise NK, Fraker TD Jr, Kisslo JA. Echocardiographic documentation of vegetative lesions in infective endocarditis: clinical implications. Circulation. 1980;61(2):374-80.</mixed-citation>
      </ref>
      <ref id="B243">
        <label>243</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Pedersen</surname>
              <given-names>WR</given-names>
            </name>
            <name>
              <surname>Walker</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Olson</surname>
              <given-names>JD</given-names>
            </name>
            <name>
              <surname>Gobel</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Lange</surname>
              <given-names>HW</given-names>
            </name>
            <name>
              <surname>Daniel</surname>
              <given-names>JA</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Value of transesophageal echocardiography as an adjunct to transthoracic echocardiography in evaluation of native and prosthetic valve endocarditis</article-title>
          <source>Chest</source>
          <year>1991</year>
          <volume>100</volume>
          <issue>2</issue>
          <fpage>351</fpage>
          <lpage>356</lpage>
        </element-citation>
        <mixed-citation>243. Pedersen WR, Walker M, Olson JD, Gobel F, Lange HW, Daniel JA et al. Value of transesophageal echocardiography as an adjunct to transthoracic echocardiography in evaluation of native and prosthetic valve endocarditis. Chest. 1991;100(2):351-6.</mixed-citation>
      </ref>
      <ref id="B244">
        <label>244</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Li</surname>
              <given-names>JS</given-names>
            </name>
            <name>
              <surname>Sexton</surname>
              <given-names>DJ</given-names>
            </name>
            <name>
              <surname>Mick</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Nettles</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Fowler</surname>
              <given-names>VG</given-names>
              <suffix>Jr</suffix>
            </name>
            <name>
              <surname>Ryan</surname>
              <given-names>T</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis</article-title>
          <source>Clin Infect Dis</source>
          <year>2000</year>
          <volume>30</volume>
          <issue>4</issue>
          <fpage>633</fpage>
          <lpage>638</lpage>
        </element-citation>
        <mixed-citation>244. Li JS, Sexton DJ, Mick N, Nettles R, Fowler VG Jr, Ryan T et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis. 2000;30(4):633-8.</mixed-citation>
      </ref>
      <ref id="B245">
        <label>245</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Slipczuk</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Codolosa</surname>
              <given-names>JN</given-names>
            </name>
            <name>
              <surname>Davila</surname>
              <given-names>CD</given-names>
            </name>
            <name>
              <surname>Romero-Corral</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Yun</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Pressman</surname>
              <given-names>GS</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Infective endocarditis epidemiology over five decades: a systematic review</article-title>
          <source>PLoS One</source>
          <year>2013</year>
          <volume>8</volume>
          <issue>12</issue>
          <elocation-id>e82665</elocation-id>
          <comment>Erratum in: PLoS One. 2014;9(10):e111564</comment>
        </element-citation>
        <mixed-citation>245. Slipczuk L, Codolosa JN, Davila CD, Romero-Corral A, Yun J, Pressman GS et al. Infective endocarditis epidemiology over five decades: a systematic review. PLoS One. 2013;8(12):e82665. Erratum in: PLoS One. 2014;9(10):e111564.</mixed-citation>
      </ref>
      <ref id="B246">
        <label>246</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Durante-Mangoni</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Bradley</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Selton-Suty</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Tripodi</surname>
              <given-names>MF</given-names>
            </name>
            <name>
              <surname>Barsic</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Bouza</surname>
              <given-names>E</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>International Collaboration on Endocarditis Prospective Cohort Study Group. Current features of infective endocarditis in elderly patients: results of the International Collaboration on Endocarditis Prospective Cohort Study</article-title>
          <source>Arch Intern Med</source>
          <year>2008</year>
          <volume>168</volume>
          <issue>19</issue>
          <fpage>2095</fpage>
          <lpage>2103</lpage>
        </element-citation>
        <mixed-citation>246. Durante-Mangoni E, Bradley S, Selton-Suty C, Tripodi MF, Barsic B, Bouza E et al.; International Collaboration on Endocarditis Prospective Cohort Study Group. Current features of infective endocarditis in elderly patients: results of the International Collaboration on Endocarditis Prospective Cohort Study. Arch Intern Med. 2008;168(19):2095-103.</mixed-citation>
      </ref>
      <ref id="B247">
        <label>247</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>High</surname>
              <given-names>KP</given-names>
            </name>
            <name>
              <surname>Bradley</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Loeb</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Palmer</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Quagliarello</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Yoshikawa</surname>
              <given-names>T</given-names>
            </name>
          </person-group>
          <article-title>A new paradigm for clinical investigation of infectious syndromes in older adults: assessment of functional status as a risk factor and outcome measure</article-title>
          <source>Clin Infect Dis</source>
          <year>2005</year>
          <volume>40</volume>
          <issue>1</issue>
          <fpage>114</fpage>
          <lpage>122</lpage>
        </element-citation>
        <mixed-citation>247. High KP, Bradley S, Loeb M, Palmer R, Quagliarello V, Yoshikawa T. A new paradigm for clinical investigation of infectious syndromes in older adults: assessment of functional status as a risk factor and outcome measure. Clin Infect Dis. 2005;40(1):114-22.</mixed-citation>
      </ref>
      <ref id="B248">
        <label>248</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Remadi</surname>
              <given-names>JP</given-names>
            </name>
            <name>
              <surname>Nadji</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Goissen</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Zomvuama</surname>
              <given-names>NA</given-names>
            </name>
            <name>
              <surname>Sorel</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Tribouilloy</surname>
              <given-names>C</given-names>
            </name>
          </person-group>
          <article-title>Infective endocarditis in elderly patients: clinical characteristics and outcome</article-title>
          <source>Eur J Cardiothorac Surg</source>
          <year>2009</year>
          <volume>35</volume>
          <issue>1</issue>
          <fpage>123</fpage>
          <lpage>129</lpage>
        </element-citation>
        <mixed-citation>248. Remadi JP, Nadji G, Goissen T, Zomvuama NA, Sorel C, Tribouilloy C. Infective endocarditis in elderly patients: clinical characteristics and outcome. Eur J Cardiothorac Surg. 2009;35(1):123-9.</mixed-citation>
      </ref>
      <ref id="B249">
        <label>249</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Baddour</surname>
              <given-names>LM</given-names>
            </name>
            <name>
              <surname>Epstein</surname>
              <given-names>AE</given-names>
            </name>
            <name>
              <surname>Erickson</surname>
              <given-names>CC</given-names>
            </name>
            <name>
              <surname>Knight</surname>
              <given-names>BP</given-names>
            </name>
            <name>
              <surname>Levison</surname>
              <given-names>ME</given-names>
            </name>
            <name>
              <surname>Lockhart</surname>
              <given-names>PB</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee; Council on Cardiovascular Disease in Young; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Nursing; Council on Clinical Cardiology; Interdisciplinary Council on Quality of Care; American Heart Association. Update on cardiovascular implantable electronic device infections and their management: a scientific statement from the American Heart Association</article-title>
          <source>Circulation</source>
          <year>2010</year>
          <volume>121</volume>
          <issue>3</issue>
          <fpage>458</fpage>
          <lpage>477</lpage>
        </element-citation>
        <mixed-citation>249. Baddour LM, Epstein AE, Erickson CC, Knight BP, Levison ME, Lockhart PB et al.; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee; Council on Cardiovascular Disease in Young; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Nursing; Council on Clinical Cardiology; Interdisciplinary Council on Quality of Care; American Heart Association. Update on cardiovascular implantable electronic device infections and their management: a scientific statement from the American Heart Association. Circulation. 2010;121(3):458-77.</mixed-citation>
      </ref>
      <ref id="B250">
        <label>250</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Gould</surname>
              <given-names>FK</given-names>
            </name>
            <name>
              <surname>Denning</surname>
              <given-names>DW</given-names>
            </name>
            <name>
              <surname>Elliott</surname>
              <given-names>TS</given-names>
            </name>
            <name>
              <surname>Foweraker</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Perry</surname>
              <given-names>JD</given-names>
            </name>
            <name>
              <surname>Prendergast</surname>
              <given-names>BD</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Working Party of the British Society for Antimicrobial Chemotherapy. Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: a report of the Working Party of the British Society for Antimicrobial Chemotherapy</article-title>
          <source>J Antimicrob Chemother</source>
          <year>2012</year>
          <volume>67</volume>
          <issue>2</issue>
          <fpage>269</fpage>
          <lpage>289</lpage>
          <comment>Erratum in: J Antimicrob Chemother. 2012;67(5):1304</comment>
        </element-citation>
        <mixed-citation>250. Gould FK, Denning DW, Elliott TS, Foweraker J, Perry JD, Prendergast BD et al.; Working Party of the British Society for Antimicrobial Chemotherapy. Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: a report of the Working Party of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother. 2012;67(2):269-89. Erratum in: J Antimicrob Chemother. 2012;67(5):1304.</mixed-citation>
      </ref>
      <ref id="B251">
        <label>251</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Baddour</surname>
              <given-names>LM</given-names>
            </name>
            <name>
              <surname>Wilson</surname>
              <given-names>WR</given-names>
            </name>
            <name>
              <surname>Bayer</surname>
              <given-names>AS</given-names>
            </name>
            <name>
              <surname>Fowler</surname>
              <given-names>VG</given-names>
              <suffix>Jr</suffix>
            </name>
            <name>
              <surname>Tleyjeh</surname>
              <given-names>IM</given-names>
            </name>
            <name>
              <surname>Rybak</surname>
              <given-names>MJ</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association</article-title>
          <source>Circulation</source>
          <year>2015</year>
          <volume>132</volume>
          <issue>15</issue>
          <fpage>1435</fpage>
          <lpage>1486</lpage>
          <comment>Erratum in: Circulation. 2015;132(17):e215. Circulation. 2016;134(8):e113</comment>
        </element-citation>
        <mixed-citation>251. Baddour LM, Wilson WR, Bayer AS, Fowler VG Jr, Tleyjeh IM, Rybak MJ et al.; American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation. 2015;132(15):1435-86. Erratum in: Circulation. 2015;132(17):e215. Circulation. 2016;134(8):e113.</mixed-citation>
      </ref>
      <ref id="B252">
        <label>252</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Forestier</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Fraisse</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Roubaud-Baudron</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Selton-Suty</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Pagani</surname>
              <given-names>L</given-names>
            </name>
          </person-group>
          <article-title>Managing infective endocarditis in the elderly: new issues for an old disease</article-title>
          <source>Clin Interv Aging</source>
          <year>2016</year>
          <month>10</month>
          <day>02</day>
          <volume>11</volume>
          <fpage>1199</fpage>
          <lpage>1206</lpage>
        </element-citation>
        <mixed-citation>252. Forestier E, Fraisse T, Roubaud-Baudron C, Selton-Suty C, Pagani L. Managing infective endocarditis in the elderly: new issues for an old disease. Clin Interv Aging. 2016 Sep 2;11:1199-206.</mixed-citation>
      </ref>
      <ref id="B253">
        <label>253</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Afilalo</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Mottillo</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Eisenberg</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Alexander</surname>
              <given-names>KP</given-names>
            </name>
            <name>
              <surname>Noiseux</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Perrault</surname>
              <given-names>LP</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Addition of frailty and disability to cardiac surgery risk scores identifies elderly patients at high risk of mortality or major morbidity</article-title>
          <source>Circ Cardiovasc Qual Outcomes</source>
          <year>2012</year>
          <volume>5</volume>
          <issue>2</issue>
          <fpage>222</fpage>
          <lpage>228</lpage>
        </element-citation>
        <mixed-citation>253. Afilalo J, Mottillo S, Eisenberg MJ, Alexander KP, Noiseux N, Perrault LP et al. Addition of frailty and disability to cardiac surgery risk scores identifies elderly patients at high risk of mortality or major morbidity. Circ Cardiovasc Qual Outcomes. 2012;5(2):222-8.</mixed-citation>
      </ref>
      <ref id="B254">
        <label>254</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Moya</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Sutton</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Ammirati</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Blanc</surname>
              <given-names>JJ</given-names>
            </name>
            <name>
              <surname>Brignole</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Dahm</surname>
              <given-names>JB</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Task Force for the Diagnosis and Management of Syncope; European Society of Cardiology (ESC); European Heart Rhythm Association (EHRA); Heart Failure Association (HFA); Heart Rhythm Society (HRS). Guidelines for the diagnosis and management of syncope (version 2009)</article-title>
          <source>Eur Heart J</source>
          <year>2009</year>
          <volume>30</volume>
          <issue>21</issue>
          <fpage>2631</fpage>
          <lpage>2671</lpage>
        </element-citation>
        <mixed-citation>254. Moya A, Sutton R, Ammirati F, Blanc JJ, Brignole M, Dahm JB et al. Task Force for the Diagnosis and Management of Syncope; European Society of Cardiology (ESC); European Heart Rhythm Association (EHRA); Heart Failure Association (HFA); Heart Rhythm Society (HRS). Guidelines for the diagnosis and management of syncope (version 2009). Eur Heart J. 2009;30(21):2631-71.</mixed-citation>
      </ref>
      <ref id="B255">
        <label>255</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ungar</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Galizia</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Morrione</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Mussi</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Noro</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Ghirelli</surname>
              <given-names>L</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Two-year morbidity and mortality in elderly patients with syncope</article-title>
          <source>Age Ageing</source>
          <year>2011</year>
          <volume>40</volume>
          <issue>6</issue>
          <fpage>696</fpage>
          <lpage>702</lpage>
        </element-citation>
        <mixed-citation>255. Ungar A, Galizia G, Morrione A, Mussi C, Noro G, Ghirelli L et al. Two-year morbidity and mortality in elderly patients with syncope. Age Ageing. 2011;40(6):696-702.</mixed-citation>
      </ref>
      <ref id="B256">
        <label>256</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Kenny</surname>
              <given-names>RA</given-names>
            </name>
            <name>
              <surname>Bhangu</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>King-Kallimanis</surname>
              <given-names>BL</given-names>
            </name>
          </person-group>
          <article-title>Epidemiology of syncope/collapse in younger and older Western patient populations</article-title>
          <source>Prog Cardiovasc Dis</source>
          <year>2013</year>
          <volume>55</volume>
          <issue>4</issue>
          <fpage>357</fpage>
          <lpage>363</lpage>
        </element-citation>
        <mixed-citation>256. Kenny RA, Bhangu J, King-Kallimanis BL. Epidemiology of syncope/collapse in younger and older Western patient populations. Prog Cardiovasc Dis. 2013;55(4):357-63.</mixed-citation>
      </ref>
      <ref id="B257">
        <label>257</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Soteriades</surname>
              <given-names>ES</given-names>
            </name>
            <name>
              <surname>Evans</surname>
              <given-names>JC</given-names>
            </name>
            <name>
              <surname>Larson</surname>
              <given-names>MG</given-names>
            </name>
            <name>
              <surname>Chen</surname>
              <given-names>MH</given-names>
            </name>
            <name>
              <surname>Chen</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Benjamin</surname>
              <given-names>EJ</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Incidence and prognosis of syncope</article-title>
          <source>N Engl J Med</source>
          <year>2002</year>
          <volume>347</volume>
          <issue>12</issue>
          <fpage>878</fpage>
          <lpage>985</lpage>
        </element-citation>
        <mixed-citation>257. Soteriades ES, Evans JC, Larson MG, Chen MH, Chen L, Benjamin EJ et al. Incidence and prognosis of syncope. N Engl J Med. 2002;347(12):878-85.</mixed-citation>
      </ref>
      <ref id="B258">
        <label>258</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Galizia</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Abete</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Mussi</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Noro</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Morrione</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Langellotto</surname>
              <given-names>A</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Role of early symptoms in assessment of syncope in elderly people: results from the Italian group for the study of syncope in the elderly</article-title>
          <source>J Am Geriatr Soc</source>
          <year>2009</year>
          <volume>57</volume>
          <issue>1</issue>
          <fpage>18</fpage>
          <lpage>23</lpage>
        </element-citation>
        <mixed-citation>258. Galizia G, Abete P, Mussi C, Noro G, Morrione A, Langellotto A et al. Role of early symptoms in assessment of syncope in elderly people: results from the Italian group for the study of syncope in the elderly. J Am Geriatr Soc. 2009;57(1):18-23.</mixed-citation>
      </ref>
      <ref id="B259">
        <label>259</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Del Rosso</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Ungar</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Maggi</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Giada</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Petix</surname>
              <given-names>NR</given-names>
            </name>
            <name>
              <surname>de Santo</surname>
              <given-names>T</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Clinical predictors of cardiac syncope at initial evaluation in patients referred urgently to a general hospital: the EGSYS score</article-title>
          <source>Heart</source>
          <year>2008</year>
          <volume>94</volume>
          <issue>12</issue>
          <fpage>1620</fpage>
          <lpage>1626</lpage>
        </element-citation>
        <mixed-citation>259. Del Rosso A, Ungar A, Maggi R, Giada F, Petix NR, De Santo T et al. Clinical predictors of cardiac syncope at initial evaluation in patients referred urgently to a general hospital: the EGSYS score. Heart. 2008;94(12):1620-6.</mixed-citation>
      </ref>
      <ref id="B260">
        <label>260</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Huff</surname>
              <given-names>JS</given-names>
            </name>
            <name>
              <surname>Decker</surname>
              <given-names>WW</given-names>
            </name>
            <name>
              <surname>Quinn</surname>
              <given-names>JV</given-names>
            </name>
            <name>
              <surname>Perron</surname>
              <given-names>AD</given-names>
            </name>
            <name>
              <surname>Napoli</surname>
              <given-names>AM</given-names>
            </name>
            <name>
              <surname>Peeters</surname>
              <given-names>S</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with syncope</article-title>
          <source>Ann Emerg Med</source>
          <year>2007</year>
          <volume>49</volume>
          <issue>4</issue>
          <fpage>431</fpage>
          <lpage>444</lpage>
        </element-citation>
        <mixed-citation>260. Huff JS, Decker WW, Quinn JV, Perron AD, Napoli AM, Peeters S et al. Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with syncope Ann Emerg Med. 2007;49(4):431-44.</mixed-citation>
      </ref>
      <ref id="B261">
        <label>261</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ungar</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Mussi</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Ceccofiglio</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Bellelli</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Nicosia</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Bo</surname>
              <given-names>M</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Etiology of syncope and unexplained falls in elderly adults with dementia: syncope and dementia (SYD) study</article-title>
          <source>J Am Geriatr Soc</source>
          <year>2016</year>
          <volume>64</volume>
          <issue>8</issue>
          <fpage>1567</fpage>
          <lpage>1573</lpage>
        </element-citation>
        <mixed-citation>261. Ungar A, Mussi C, Ceccofiglio A, Bellelli G, Nicosia F, Bo M et al. Etiology of syncope and unexplained falls in elderly adults with dementia: syncope and dementia (SYD) study. J Am Geriatr Soc. 2016;64(8):1567-73.</mixed-citation>
      </ref>
      <ref id="B262">
        <label>262</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Woon</surname>
              <given-names>VC</given-names>
            </name>
            <name>
              <surname>Lim</surname>
              <given-names>KH</given-names>
            </name>
          </person-group>
          <article-title>Acute myocardial infarction in the elderly--the differences compared with the young</article-title>
          <source>Singapore Med J</source>
          <year>2003</year>
          <volume>44</volume>
          <issue>8</issue>
          <fpage>414</fpage>
          <lpage>418</lpage>
        </element-citation>
        <mixed-citation>262. Woon VC, Lim KH. Acute myocardial infarction in the elderly--the differences compared with the young. Singapore Med J. 2003;44(8):414-8.</mixed-citation>
      </ref>
      <ref id="B263">
        <label>263</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bayer</surname>
              <given-names>AJ</given-names>
            </name>
            <name>
              <surname>Chadha</surname>
              <given-names>JS</given-names>
            </name>
            <name>
              <surname>Farag</surname>
              <given-names>RR</given-names>
            </name>
            <name>
              <surname>Pathy</surname>
              <given-names>MS</given-names>
            </name>
          </person-group>
          <article-title>Changing presentation of myocardial infraction with increasing old age</article-title>
          <source>J Am Geriatr Soc</source>
          <year>1986</year>
          <volume>34</volume>
          <issue>4</issue>
          <fpage>263</fpage>
          <lpage>266</lpage>
        </element-citation>
        <mixed-citation>263. Bayer AJ, Chadha JS, Farag RR, Pathy MS. Changing presentation of myocardial infraction with increasing old age. J Am Geriatr Soc. 1986;34(4):263-6.</mixed-citation>
      </ref>
      <ref id="B264">
        <label>264</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Timmons</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Kingston</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Hussain</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Kelly</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Liston</surname>
              <given-names>R</given-names>
            </name>
          </person-group>
          <article-title>Pulmonary embolism: differences in presentation between older and younger patients</article-title>
          <source>Age Ageing</source>
          <year>2004</year>
          <volume>32</volume>
          <issue>6</issue>
          <fpage>601</fpage>
          <lpage>605</lpage>
        </element-citation>
        <mixed-citation>264. Timmons S, Kingston M, Hussain M, Kelly H, Liston R. Pulmonary embolism: differences in presentation between older and younger patients. Age Ageing. 2004;32(6):601-5.</mixed-citation>
      </ref>
      <ref id="B265">
        <label>265</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Nallamothu</surname>
              <given-names>BK</given-names>
            </name>
            <name>
              <surname>Mehta</surname>
              <given-names>RH</given-names>
            </name>
            <name>
              <surname>Saint</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Llovet</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Bossone</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Cooper</surname>
              <given-names>JV</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Syncope in acute aortic dissection: diagnostic, prognostic, and clinical implications</article-title>
          <source>Am J Med</source>
          <year>2002</year>
          <volume>113</volume>
          <issue>6</issue>
          <fpage>468</fpage>
          <lpage>471</lpage>
        </element-citation>
        <mixed-citation>265. Nallamothu BK, Mehta RH, Saint S, Llovet A, Bossone E, Cooper JV et al. Syncope in acute aortic dissection: diagnostic, prognostic, and clinical implications. Am J Med. 2002;113(6):468-71.</mixed-citation>
      </ref>
      <ref id="B266">
        <label>266</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Martin</surname>
              <given-names>TP</given-names>
            </name>
            <name>
              <surname>Hanusa</surname>
              <given-names>BH</given-names>
            </name>
            <name>
              <surname>Kapoor</surname>
              <given-names>WN</given-names>
            </name>
          </person-group>
          <article-title>Risk stratification of patients with syncope</article-title>
          <source>Ann Emerg Med</source>
          <year>1997</year>
          <volume>29</volume>
          <issue>4</issue>
          <fpage>459</fpage>
          <lpage>466</lpage>
        </element-citation>
        <mixed-citation>266. Martin TP, Hanusa BH, Kapoor WN. Risk stratification of patients with syncope. Ann Emerg Med. 1997;29(4):459-66.</mixed-citation>
      </ref>
      <ref id="B267">
        <label>267</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Costantino</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Perego</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Dipaola</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Borella</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Galli</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Cantoni</surname>
              <given-names>G</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>STePS Investigators. Short- and long-term prognosis of syncope, risk factors, and role of hospital admission results from the STePS (Short-Term Prognosis of Syncope) study</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2008</year>
          <volume>51</volume>
          <issue>3</issue>
          <fpage>276</fpage>
          <lpage>283</lpage>
        </element-citation>
        <mixed-citation>267. Costantino G, Perego F, Dipaola F, Borella M, Galli A, Cantoni G et al.; STePS Investigators. Short- and long-term prognosis of syncope, risk factors, and role of hospital admission results from the STePS (Short-Term Prognosis of Syncope) study. J Am Coll Cardiol. 2008;51(3):276-83.</mixed-citation>
      </ref>
      <ref id="B268">
        <label>268</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Di Marco</surname>
              <given-names>JP</given-names>
            </name>
            <name>
              <surname>Philbrick</surname>
              <given-names>JT</given-names>
            </name>
          </person-group>
          <article-title>Use of ambulatory electrocardiographic (Holter) monitoring</article-title>
          <source>Ann Intern Med</source>
          <year>1990</year>
          <volume>113</volume>
          <issue>1</issue>
          <fpage>53</fpage>
          <lpage>68</lpage>
        </element-citation>
        <mixed-citation>268. Di Marco JP, Philbrick JT. Use of ambulatory electrocardiographic (Holter) monitoring. Ann Intern Med. 1990;113(1):53-68.</mixed-citation>
      </ref>
      <ref id="B269">
        <label>269</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Bigger</surname>
              <given-names>JT</given-names>
            </name>
            <name>
              <surname>Rolnitzky</surname>
              <given-names>LM</given-names>
            </name>
            <name>
              <surname>Leahey</surname>
              <given-names>EB</given-names>
            </name>
            <name>
              <surname>LaPook</surname>
              <given-names>JD</given-names>
            </name>
          </person-group>
          <source>Duration of recording; activity protocol</source>
          <person-group person-group-type="editor">
            <name>
              <surname>Wenger</surname>
              <given-names>NK</given-names>
            </name>
            <name>
              <surname>Nock</surname>
              <given-names>MB</given-names>
            </name>
            <name>
              <surname>Ringquist</surname>
              <given-names>I</given-names>
            </name>
          </person-group>
          <publisher-loc>Chicago</publisher-loc>
          <publisher-name>Year Book Medical</publisher-name>
          <comment>Publishers Inc</comment>
          <year>1981</year>
          <fpage>87</fpage>
          <lpage>102</lpage>
        </element-citation>
        <mixed-citation>269. Bigger JT, Rolnitzky LM, Leahey EB, LaPook JD. Duration of recording; activity protocol. In: Wenger NK, Nock MB and Ringquist I. Chicago: Year Book Medical. Publishers Inc; 1981. p. 87-102.</mixed-citation>
      </ref>
      <ref id="B270">
        <label>270</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Zeldis</surname>
              <given-names>SM</given-names>
            </name>
            <name>
              <surname>Levine</surname>
              <given-names>BJ</given-names>
            </name>
            <name>
              <surname>Michelson</surname>
              <given-names>EL</given-names>
            </name>
            <name>
              <surname>Morganroth</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Cardiovascular complaints: Correlation with cardiac arrhythmias on 24-hour electrocardiographic monitoring</article-title>
          <source>Chest</source>
          <year>1980</year>
          <volume>78</volume>
          <fpage>456</fpage>
          <lpage>461</lpage>
        </element-citation>
        <mixed-citation>270. Zeldis SM, Levine BJ, Michelson EL, Morganroth J. Cardiovascular complaints: Correlation with cardiac arrhythmias on 24-hour electrocardiographic monitoring. Chest. 1980;78:456-61.</mixed-citation>
      </ref>
      <ref id="B271">
        <label>271</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Clark</surname>
              <given-names>PI</given-names>
            </name>
            <name>
              <surname>Glasser</surname>
              <given-names>SP</given-names>
            </name>
            <name>
              <surname>Spoto</surname>
              <given-names>E</given-names>
              <suffix>Jr</suffix>
            </name>
          </person-group>
          <article-title>Arrhythmias detected by ambulatory monitoring: lack of correlation with symptoms of dizziness and syncope</article-title>
          <source>Chest</source>
          <year>1980</year>
          <volume>77</volume>
          <issue>6</issue>
          <fpage>722</fpage>
          <lpage>725</lpage>
        </element-citation>
        <mixed-citation>271. Clark PI, Glasser SP, Spoto E Jr. Arrhythmias detected by ambulatory monitoring: lack of correlation with symptoms of dizziness and syncope. Chest. 1980;77(6):722-5.</mixed-citation>
      </ref>
      <ref id="B272">
        <label>272</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Zimetbaum</surname>
              <given-names>PJ</given-names>
            </name>
            <name>
              <surname>Josephson</surname>
              <given-names>ME</given-names>
            </name>
          </person-group>
          <article-title>Evaluation of patients with palpitations</article-title>
          <source>N Engl J Med</source>
          <year>1998</year>
          <volume>388</volume>
          <issue>19</issue>
          <fpage>1369</fpage>
          <lpage>1373</lpage>
        </element-citation>
        <mixed-citation>272. Zimetbaum PJ, Josephson ME. Evaluation of patients with palpitations. N Engl J Med. 1998;388(19):1369-73.</mixed-citation>
      </ref>
      <ref id="B273">
        <label>273</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Kus</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Nadeau</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Costi</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Molin</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Primeau</surname>
              <given-names>R</given-names>
            </name>
          </person-group>
          <article-title>Comparison of the diagnostic yield of Holter versus transtelephonic monitoring</article-title>
          <source>Can J Cardiol</source>
          <year>1995</year>
          <volume>11</volume>
          <issue>10</issue>
          <fpage>891</fpage>
          <lpage>894</lpage>
        </element-citation>
        <mixed-citation>273. Kus T, Nadeau R, Costi P, Molin F, Primeau R. Comparison of the diagnostic yield of Holter versus transtelephonic monitoring. Can J Cardiol. 1995;11(10):891-4.</mixed-citation>
      </ref>
      <ref id="B274">
        <label>274</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Kinlay</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Leitch</surname>
              <given-names>JW</given-names>
            </name>
            <name>
              <surname>Neil</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Chapman</surname>
              <given-names>BL</given-names>
            </name>
            <name>
              <surname>Hardy</surname>
              <given-names>DB</given-names>
            </name>
            <name>
              <surname>Fletcher</surname>
              <given-names>PJ</given-names>
            </name>
          </person-group>
          <article-title>Cardiac event recorders yield more diagnoses and are more cost- effective than 48 &#8211; hour Holter monitoring in patients with palpitations. A controlled clinical trial</article-title>
          <source>Ann Intern Med</source>
          <year>1996</year>
          <volume>124</volume>
          <issue>1 Pt 1</issue>
          <fpage>16</fpage>
          <lpage>20</lpage>
        </element-citation>
        <mixed-citation>274. Kinlay S, Leitch JW, Neil A, Chapman BL, Hardy DB, Fletcher PJ. Cardiac event recorders yield more diagnoses and are more cost- effective than 48 &#8211; hour Holter monitoring in patients with palpitations. A controlled clinical trial. Ann Intern Med. 1996;124(1 Pt 1):16-20.</mixed-citation>
      </ref>
      <ref id="B275">
        <label>275</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Cherin</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Colvez</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Deville de Periere</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Sereni</surname>
              <given-names>D</given-names>
            </name>
          </person-group>
          <article-title>Risk of syncope in the elderly and consumption of drugs: a case-control study</article-title>
          <source>J Clin Epidemiol</source>
          <year>1997</year>
          <volume>50</volume>
          <issue>3</issue>
          <fpage>313</fpage>
          <lpage>320</lpage>
        </element-citation>
        <mixed-citation>275. Cherin P, Colvez A, Deville de Periere G, Sereni D. Risk of syncope in the elderly and consumption of drugs: a case-control study. J Clin Epidemiol.1997;50(3):313-20.</mixed-citation>
      </ref>
      <ref id="B276">
        <label>276</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Volkert</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Kreuel</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Stehle</surname>
              <given-names>P</given-names>
            </name>
          </person-group>
          <article-title>Fluid intake of community-living, independent elderly in German--a nationwide, representative study</article-title>
          <source>J Nutr Health Aging</source>
          <year>2005</year>
          <volume>9</volume>
          <issue>5</issue>
          <fpage>305</fpage>
          <lpage>309</lpage>
        </element-citation>
        <mixed-citation>276. Volkert D, Kreuel K, Stehle P. Fluid intake of community-living, independent elderly in German--a nationwide, representative study. J Nutr Health Aging. 2005;9(5):305-9.</mixed-citation>
      </ref>
      <ref id="B277">
        <label>277</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Chen</surname>
              <given-names>LY</given-names>
            </name>
            <name>
              <surname>Shen</surname>
              <given-names>WK</given-names>
            </name>
          </person-group>
          <article-title>Neurocardiogenic syncope: latest pharmacological therapies</article-title>
          <source>Expert Opin Pharmacother</source>
          <year>2006</year>
          <volume>7</volume>
          <issue>9</issue>
          <fpage>1151</fpage>
          <lpage>1162</lpage>
        </element-citation>
        <mixed-citation>277. Chen LY, Shen WK. Neurocardiogenic syncope: latest pharmacological therapies. Expert Opin Pharmacother. 2006;7(9):1151-62.</mixed-citation>
      </ref>
      <ref id="B278">
        <label>278</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Hood</surname>
              <given-names>R</given-names>
            </name>
          </person-group>
          <article-title>Syncope in the elderly</article-title>
          <source>Clin Geriatr Med</source>
          <year>2007</year>
          <volume>23</volume>
          <issue>2</issue>
          <fpage>351</fpage>
          <lpage>361</lpage>
        </element-citation>
        <mixed-citation>278. Hood R. Syncope in the elderly. Clin Geriatr Med. 2007;23(2):351-61.</mixed-citation>
      </ref>
      <ref id="B279">
        <label>279</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Sutton</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Brignole</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Menozzi</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Raviele</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Alboni</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Giani</surname>
              <given-names>P</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Dual-chamber pacing in treatment of neurally-mediated tilt-positive cardioinhibitory syncope. Pacemaker versus no therapy: a multicentre randomized study. The Vasovagal Syncope International Study (VASIS) Investigators</article-title>
          <source>Circulation</source>
          <year>2000</year>
          <volume>102</volume>
          <issue>3</issue>
          <fpage>294</fpage>
          <lpage>299</lpage>
        </element-citation>
        <mixed-citation>279. Sutton R, Brignole M, Menozzi C, Raviele A, Alboni P, Giani P et al. Dual-chamber pacing in treatment of neurally-mediated tilt-positive cardioinhibitory syncope. Pacemaker versus no therapy: a multicentre randomized study. The Vasovagal Syncope International Study (VASIS) Investigators. Circulation. 2000;102(3):294-9.</mixed-citation>
      </ref>
      <ref id="B280">
        <label>280</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Epstein</surname>
              <given-names>AE</given-names>
            </name>
            <name>
              <surname>DiMarco</surname>
              <given-names>JP</given-names>
            </name>
            <name>
              <surname>Ellenbogen</surname>
              <given-names>KA</given-names>
            </name>
            <name>
              <surname>Estes</surname>
              <given-names>NA</given-names>
              <suffix>3rd</suffix>
            </name>
            <name>
              <surname>Freedman</surname>
              <given-names>RA</given-names>
            </name>
            <name>
              <surname>Gettes</surname>
              <given-names>LS</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices); American Association for Thoracic Surgery; Society of Thoracic Surgeons. ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices)</article-title>
          <source>Circulation</source>
          <year>2008</year>
          <volume>117</volume>
          <issue>21</issue>
          <fpage>e350</fpage>
          <lpage>e408</lpage>
          <comment>Erratum in: Circulation. 2009; 120(5):e34-5</comment>
        </element-citation>
        <mixed-citation>280. Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA 3rd, Freedman RA, Gettes LS et al.; American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices); American Association for Thoracic Surgery; Society of Thoracic Surgeons. ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices). Circulation. 2008;117(21):e350-408. Erratum in: Circulation. 2009; 120(5):e34-5</mixed-citation>
      </ref>
      <ref id="B281">
        <label>281</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Scanavacca</surname>
              <given-names>MI</given-names>
            </name>
            <name>
              <surname>de Brito</surname>
              <given-names>FS</given-names>
            </name>
            <name>
              <surname>Maia</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Hachul</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Gizzi</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Lorga</surname>
              <given-names>A</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Guidelines for the evaluation and treatment of patients with cardiac arrhythmias</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2002</year>
          <volume>79</volume>
          <supplement>Suppl 5</supplement>
          <fpage>1</fpage>
          <lpage>50</lpage>
        </element-citation>
        <mixed-citation>281. Scanavacca MI, de Brito FS, Maia I, Hachul D, Gizzi J, Lorga A et al. [Guidelines for the evaluation and treatment of patients with cardiac arrhythmias]. Arq Bras Cardiol. 2002;79 Suppl 5:1-50.</mixed-citation>
      </ref>
      <ref id="B282">
        <label>282</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Lamas</surname>
              <given-names>GA</given-names>
            </name>
            <name>
              <surname>Knight</surname>
              <given-names>JD</given-names>
            </name>
            <name>
              <surname>Sweeney</surname>
              <given-names>MO</given-names>
            </name>
            <name>
              <surname>Mianulli</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Jorapur</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Khalighi</surname>
              <given-names>K</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Impact of rate-modulated pacing on quality of life and exercise capacity: evidence from the Advanced Elements of Pacing Randomized Controlled Trial (ADEPT)</article-title>
          <source>Heart Rhythm</source>
          <year>2007</year>
          <volume>4</volume>
          <issue>9</issue>
          <fpage>1125</fpage>
          <lpage>1132</lpage>
        </element-citation>
        <mixed-citation>282. Lamas GA, Knight JD, Sweeney MO, Mianulli M, Jorapur V, Khalighi K et al. Impact of rate-modulated pacing on quality of life and exercise capacity: evidence from the Advanced Elements of Pacing Randomized Controlled Trial (ADEPT). Heart Rhythm. 2007;4(9):1125-32.</mixed-citation>
      </ref>
      <ref id="B283">
        <label>283</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Gammage</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Schofield</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Rankin</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Bennett</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Coles</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Pentecost</surname>
              <given-names>B</given-names>
            </name>
          </person-group>
          <article-title>Benefit of single setting rate responsive ventricular pacing compared with fixed rate demand pacing in elderly patients</article-title>
          <source>Pacing Clin Electrophysiol</source>
          <year>1991</year>
          <volume>14</volume>
          <issue>2 Pt 1</issue>
          <fpage>174</fpage>
          <lpage>180</lpage>
        </element-citation>
        <mixed-citation>283. Gammage M, Schofield S, Rankin I, Bennett M, Coles P, Pentecost B. Benefit of single setting rate responsive ventricular pacing compared with fixed rate demand pacing in elderly patients. Pacing Clin Electrophysiol. 1991;14(2 Pt 1):174-80.</mixed-citation>
      </ref>
      <ref id="B284">
        <label>284</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Berry</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Rankin</surname>
              <given-names>AC</given-names>
            </name>
            <name>
              <surname>Brady</surname>
              <given-names>AJ</given-names>
            </name>
          </person-group>
          <article-title>Bradycardia and tachycardia occurring in older people: an introduction</article-title>
          <source>Br J Cardiol</source>
          <year>2004</year>
          <volume>11</volume>
          <issue>1</issue>
          <fpage>61</fpage>
          <lpage>64</lpage>
        </element-citation>
        <mixed-citation>284. Berry C, Rankin AC, Brady AJ. Bradycardia and tachycardia occurring in older people: an introduction. Br J Cardiol. 2004;11(1):61-4.</mixed-citation>
      </ref>
      <ref id="B285">
        <label>285</label>
        <element-citation publication-type="webpage">
          <person-group person-group-type="author">
            <collab>Arrhythmias and conduction disturbances</collab>
          </person-group>
          <article-title>The Merck Manual of Geriatrics</article-title>
          <date-in-citation content-type="access-date">2018 Jan 10</date-in-citation>
          <comment>Available from: <ext-link ext-link-type="uri" xlink:href="http://www.merck.com/mrkshared/mm_geriatrics/sec11/ch91.jsp">http://www.merck.com/mrkshared/mm_geriatrics/sec11/ch91.jsp</ext-link></comment>
        </element-citation>
        <mixed-citation>285. Arrhythmias and conduction disturbances. In: The Merck Manual of Geriatrics. [Internet]. [Cited in 2018 Jan 10]. Available from: <ext-link ext-link-type="uri" xlink:href="http://www.merck.com/mrkshared/mm_geriatrics/sec11/ch91.jsp">http://www.merck.com/mrkshared/mm_geriatrics/sec11/ch91.jsp</ext-link>.</mixed-citation>
      </ref>
      <ref id="B286">
        <label>286</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Fleg</surname>
              <given-names>JL</given-names>
            </name>
            <name>
              <surname>Kennedy</surname>
              <given-names>HL</given-names>
            </name>
          </person-group>
          <article-title>Cardiac arrhythmias in a healthy elderly population: detection by 24-hour ambulatory electrocardiography</article-title>
          <source>Chest</source>
          <year>1982</year>
          <volume>81</volume>
          <issue>3</issue>
          <fpage>302</fpage>
          <lpage>307</lpage>
        </element-citation>
        <mixed-citation>286. Fleg JL, Kennedy HL. Cardiac arrhythmias in a healthy elderly population: detection by 24-hour ambulatory electrocardiography. Chest. 1982;81(3):302-7.</mixed-citation>
      </ref>
      <ref id="B287">
        <label>287</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Andr&#233;n</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Lind</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Hedenstierna</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Lithell</surname>
              <given-names>H</given-names>
            </name>
          </person-group>
          <article-title>Impaired systolic and diastolic function and ventricular arrhythmia are common in normotensive healthy elderly men with left ventricular hypertrophy</article-title>
          <source>Coron Artery Dis</source>
          <year>1999</year>
          <volume>10</volume>
          <issue>2</issue>
          <fpage>111</fpage>
          <lpage>117</lpage>
        </element-citation>
        <mixed-citation>287. Andr&#233;n B, Lind L, Hedenstierna G, Lithell H. Impaired systolic and diastolic function and ventricular arrhythmia are common in normotensive healthy elderly men with left ventricular hypertrophy. Coron Artery Dis. 1999;10(2):111-7.</mixed-citation>
      </ref>
      <ref id="B288">
        <label>288</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Saviolli</surname>
              <given-names>FS</given-names>
              <suffix>Neto</suffix>
            </name>
            <name>
              <surname>Batlouni</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Guedes Mdo</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Armaganijan</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Faludi</surname>
              <given-names>AA</given-names>
            </name>
          </person-group>
          <article-title>[Cardiac arrhythmia in healthy elderly subjects: detection by dynamic electrocardiography]</article-title>
          <source>Arq Bras Cardiol</source>
          <year>1988</year>
          <volume>51</volume>
          <issue>5</issue>
          <fpage>373</fpage>
          <lpage>375</lpage>
        </element-citation>
        <mixed-citation>288. Saviolli Neto FS, Batlouni M, Guedes Mdo C, Armaganijan D, Faludi AA. [Cardiac arrhythmia in healthy elderly subjects: detection by dynamic electrocardiography]. Arq Bras Cardiol. 1988;51(5):373-5.</mixed-citation>
      </ref>
      <ref id="B289">
        <label>289</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Chandra</surname>
              <given-names>VS</given-names>
            </name>
            <name>
              <surname>Purday</surname>
              <given-names>JP</given-names>
            </name>
            <name>
              <surname>Macmillan</surname>
              <given-names>NC</given-names>
            </name>
            <name>
              <surname>Taylor</surname>
              <given-names>DJ</given-names>
            </name>
          </person-group>
          <article-title>Rhythm disorders in healthy elderly people</article-title>
          <source>Geriatr Cardiovasc Med</source>
          <year>1988</year>
          <volume>1</volume>
          <fpage>263</fpage>
          <lpage>266</lpage>
        </element-citation>
        <mixed-citation>289. Chandra VS, Purday JP, Macmillan NC, Taylor DJ. Rhythm disorders in healthy elderly people. Geriatr Cardiovasc Med. 1988;1:263-6.</mixed-citation>
      </ref>
      <ref id="B290">
        <label>290</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Tresch</surname>
              <given-names>DD</given-names>
            </name>
          </person-group>
          <article-title>Evaluation and management of cardiac arrhythmias in the elderly</article-title>
          <source>Med Clin North Am</source>
          <year>2001</year>
          <volume>85</volume>
          <issue>2</issue>
          <fpage>527</fpage>
          <lpage>550</lpage>
        </element-citation>
        <mixed-citation>290. Tresch DD. Evaluation and management of cardiac arrhythmias in the elderly. Med Clin North Am. 2001;85(2):527-50.</mixed-citation>
      </ref>
      <ref id="B291">
        <label>291</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ojeda</surname>
              <given-names>LAL</given-names>
            </name>
          </person-group>
          <article-title>Arritmias cardiacas en los ancianos</article-title>
          <source>Arch Cardiol (Mexico)</source>
          <year>2002</year>
          <volume>72</volume>
          <supplement>supl</supplement>
          <fpage>S106</fpage>
          <lpage>S110</lpage>
        </element-citation>
        <mixed-citation>291. Ojeda LAL. Arritmias cardiacas en los ancianos. Arch Cardiol (Mexico). 2002;72(supl):S106-S110.</mixed-citation>
      </ref>
      <ref id="B292">
        <label>292</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Dreifus</surname>
              <given-names>LS</given-names>
            </name>
            <name>
              <surname>Pollak</surname>
              <given-names>SJ</given-names>
            </name>
          </person-group>
          <article-title>Ablation therapy of supraventricular tachycardia in elderly persons</article-title>
          <source>Am J Geriatr Cardiol</source>
          <year>2005</year>
          <volume>14</volume>
          <issue>1</issue>
          <fpage>20</fpage>
          <lpage>25</lpage>
        </element-citation>
        <mixed-citation>292. Dreifus LS, Pollak SJ. Ablation therapy of supraventricular tachycardia in elderly persons. Am J Geriatr Cardiol. 2005;14(1):20-5.</mixed-citation>
      </ref>
      <ref id="B293">
        <label>293</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Haghjoo</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Arya</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Heidari</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Fazelifar</surname>
              <given-names>AF</given-names>
            </name>
            <name>
              <surname>Sadr-Ameli</surname>
              <given-names>MA</given-names>
            </name>
          </person-group>
          <article-title>Electrophysiologic characteristics and results of radiofrequency catheter ablation in elderly patients with atrioventricular nodal reentrant tachycardia</article-title>
          <source>J Electrocardiol</source>
          <year>2007</year>
          <volume>40</volume>
          <issue>2</issue>
          <fpage>208</fpage>
          <lpage>213</lpage>
        </element-citation>
        <mixed-citation>293. Haghjoo M, Arya A, Heidari A, Fazelifar AF, Sadr-Ameli MA. Electrophysiologic characteristics and results of radiofrequency catheter ablation in elderly patients with atrioventricular nodal reentrant tachycardia. J Electrocardiol. 2007;40(2):208-13.</mixed-citation>
      </ref>
      <ref id="B294">
        <label>294</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Zado</surname>
              <given-names>ES</given-names>
            </name>
            <name>
              <surname>Callans</surname>
              <given-names>DJ</given-names>
            </name>
            <name>
              <surname>Gottlieb</surname>
              <given-names>CD</given-names>
            </name>
            <name>
              <surname>Kutalek</surname>
              <given-names>SP</given-names>
            </name>
            <name>
              <surname>Wilbur</surname>
              <given-names>SL</given-names>
            </name>
            <name>
              <surname>Samuels</surname>
              <given-names>FL</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Efficacy and safety of catheter ablation in octogenarians</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2000</year>
          <volume>35</volume>
          <issue>2</issue>
          <fpage>458</fpage>
          <lpage>462</lpage>
        </element-citation>
        <mixed-citation>294. Zado ES, Callans DJ, Gottlieb CD, Kutalek SP, Wilbur SL, Samuels FL et al. Efficacy and safety of catheter ablation in octogenarians. J Am Coll Cardiol. 2000;35(2):458-62.</mixed-citation>
      </ref>
      <ref id="B295">
        <label>295</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Kihel</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Da Costa</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Kihel</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Rom&#233;yer-Bouchard</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Th&#233;venin</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Gonthier</surname>
              <given-names>R</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Long-term efficacy and safety of radiofrequency ablation in elderly patients with atrioventricular nodal re-entrant tachycardia</article-title>
          <source>Europace</source>
          <year>2006</year>
          <volume>8</volume>
          <issue>6</issue>
          <fpage>416</fpage>
          <lpage>420</lpage>
        </element-citation>
        <mixed-citation>295. Kihel J, Da Costa A, Kihel A, Rom&#233;yer-Bouchard C, Th&#233;venin J, Gonthier R et al. Long-term efficacy and safety of radiofrequency ablation in elderly patients with atrioventricular nodal re-entrant tachycardia. Europace. 2006;8(6):416-20.</mixed-citation>
      </ref>
      <ref id="B296">
        <label>296</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Page</surname>
              <given-names>RL</given-names>
            </name>
            <name>
              <surname>Joglar</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Caldwell</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Calkins</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Conti</surname>
              <given-names>JB</given-names>
            </name>
            <name>
              <surname>Deal</surname>
              <given-names>BJ</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2016</year>
          <volume>67</volume>
          <issue>13</issue>
          <fpage>e27</fpage>
          <lpage>e115</lpage>
        </element-citation>
        <mixed-citation>296. Page RL, Joglar JA, Caldwell MA, Calkins H, Conti JB, Deal BJ et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2016;67(13):e27-115.</mixed-citation>
      </ref>
      <ref id="B297">
        <label>297</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Priori</surname>
              <given-names>SG</given-names>
            </name>
            <name>
              <surname>Blomstr&#246;m-Lundqvist</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Mazzanti</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Blom</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Borggrefe</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Camm</surname>
              <given-names>J</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>ESC Scientific Document Group. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC)</article-title>
          <source>Eur Heart J</source>
          <year>2015</year>
          <volume>36</volume>
          <issue>41</issue>
          <fpage>2793</fpage>
          <lpage>2867</lpage>
        </element-citation>
        <mixed-citation>297. Priori SG, Blomstr&#246;m-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J et al.; ESC Scientific Document Group. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J. 2015;36(41):2793-867.</mixed-citation>
      </ref>
      <ref id="B298">
        <label>298</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Kannel</surname>
              <given-names>WB</given-names>
            </name>
            <name>
              <surname>Abbott</surname>
              <given-names>RD</given-names>
            </name>
            <name>
              <surname>Savage</surname>
              <given-names>DD</given-names>
            </name>
            <name>
              <surname>McNamara</surname>
              <given-names>PM</given-names>
            </name>
          </person-group>
          <article-title>Epidemiologic features of chronic atrial fibrillation: the Framingham study</article-title>
          <source>N Engl J Med</source>
          <year>1982</year>
          <volume>306</volume>
          <issue>17</issue>
          <fpage>1018</fpage>
          <lpage>1022</lpage>
        </element-citation>
        <mixed-citation>298. Kannel WB, Abbott RD, Savage DD, McNamara PM. Epidemiologic features of chronic atrial fibrillation: the Framingham study. N Engl J Med. 1982;306(17):1018-22.</mixed-citation>
      </ref>
      <ref id="B299">
        <label>299</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Cheitlin</surname>
              <given-names>MD</given-names>
            </name>
            <name>
              <surname>Zipes</surname>
              <given-names>DP</given-names>
            </name>
          </person-group>
          <chapter-title>Cardiovascular Disease in the Elderly</chapter-title>
          <source>Braunwald heart disease. a textbook of cardiovascular medicine</source>
          <edition>6th</edition>
          <publisher-loc>New York</publisher-loc>
          <publisher-name>Elsevier</publisher-name>
          <year>2001</year>
          <fpage>2019</fpage>
          <lpage>2037</lpage>
        </element-citation>
        <mixed-citation>299. Cheitlin MD, Zipes DP. Cardiovascular Disease in the Elderly. In: Braunwald heart disease. a textbook of cardiovascular medicine. 6th ed. New York: Elsevier; 2001. p. 2019-37.</mixed-citation>
      </ref>
      <ref id="B300">
        <label>300</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Vlietstra</surname>
              <given-names>RE</given-names>
            </name>
          </person-group>
          <article-title>Optimal investigation of the elderly and very elderly patient with atrial fibrillation: what must be done?</article-title>
          <source>Am J Geriatr Cardiol</source>
          <year>2002</year>
          <volume>11</volume>
          <issue>6</issue>
          <fpage>376</fpage>
          <lpage>379</lpage>
        </element-citation>
        <mixed-citation>300. Vlietstra RE. Optimal investigation of the elderly and very elderly patient with atrial fibrillation: what must be done? Am J Geriatr Cardiol. 2002;11(6):376-9.</mixed-citation>
      </ref>
      <ref id="B301">
        <label>301</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Dayer</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Hardman</surname>
              <given-names>SM</given-names>
            </name>
          </person-group>
          <article-title>Special problems with antiarrhythmic drugs in the elderly: safety, tolerability, and efficacy</article-title>
          <source>Am J Geriatr Cardiol</source>
          <year>2002</year>
          <volume>11</volume>
          <issue>6</issue>
          <fpage>370</fpage>
          <lpage>375</lpage>
        </element-citation>
        <mixed-citation>301. Dayer M, Hardman SM. Special problems with antiarrhythmic drugs in the elderly: safety, tolerability, and efficacy. Am J Geriatr Cardiol. 2002;11(6):370-5.</mixed-citation>
      </ref>
      <ref id="B302">
        <label>302</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Berry</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Rae</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Taylor</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Brady</surname>
              <given-names>AJ</given-names>
            </name>
          </person-group>
          <article-title>Atrial fibrillation in the elderly</article-title>
          <source>Br J Cardiol</source>
          <year>2003</year>
          <volume>10</volume>
          <fpage>373</fpage>
          <lpage>378</lpage>
        </element-citation>
        <mixed-citation>302. Berry C, Rae A, Taylor J, Brady AJ. Atrial fibrillation in the elderly. Br J Cardiol. 2003;10:373-8.</mixed-citation>
      </ref>
      <ref id="B303">
        <label>303</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Cintra</surname>
              <given-names>FD</given-names>
            </name>
            <name>
              <surname>Leite</surname>
              <given-names>RP</given-names>
            </name>
            <name>
              <surname>Storti</surname>
              <given-names>LJ</given-names>
            </name>
            <name>
              <surname>Bittencourt</surname>
              <given-names>LA</given-names>
            </name>
            <name>
              <surname>Poyares</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Castro</surname>
              <given-names>LD</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Sleep apnea and nocturnal cardiac arrhythmia: a populational study</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2014</year>
          <volume>103</volume>
          <issue>5</issue>
          <fpage>368</fpage>
          <lpage>374</lpage>
        </element-citation>
        <mixed-citation>303. Cintra FD, Leite RP, Storti LJ, Bittencourt LA, Poyares D, Castro LD et al. Sleep apnea and nocturnal cardiac arrhythmia: a populational study. Arq Bras Cardiol. 2014;103(5):368-74.</mixed-citation>
      </ref>
      <ref id="B304">
        <label>304</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Podrid</surname>
              <given-names>PJ</given-names>
            </name>
          </person-group>
          <article-title>Atrial fibrillation in the elderly</article-title>
          <source>Cardiol Clin</source>
          <year>1999</year>
          <volume>17</volume>
          <issue>1</issue>
          <fpage>173</fpage>
          <lpage>188</lpage>
        </element-citation>
        <mixed-citation>304. Podrid PJ. Atrial fibrillation in the elderly. Cardiol Clin. 1999;17(1):173-88.</mixed-citation>
      </ref>
      <ref id="B305">
        <label>305</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ruig&#243;mez</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Johansson</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Wallander</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Edvardsson</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Garc&#237;a Rodr&#237;guez</surname>
              <given-names>LA</given-names>
            </name>
          </person-group>
          <article-title>Risk of cardiovascular and cerebrovascular events after atrial fibrillation diagnosis</article-title>
          <source>Int J Cardiol</source>
          <year>2009</year>
          <volume>136</volume>
          <issue>2</issue>
          <fpage>186</fpage>
          <lpage>192</lpage>
        </element-citation>
        <mixed-citation>305. Ruig&#243;mez A, Johansson S, Wallander MA, Edvardsson N, Garc&#237;a Rodr&#237;guez LA. Risk of cardiovascular and cerebrovascular events after atrial fibrillation diagnosis. Int J Cardiol. 2009;136(2):186-92.</mixed-citation>
      </ref>
      <ref id="B306">
        <label>306</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Aronow</surname>
              <given-names>WS</given-names>
            </name>
          </person-group>
          <article-title>Management of the older person with atrial fibrillation</article-title>
          <source>J Gerontol A Biol Sci Med Sci</source>
          <year>2002</year>
          <volume>57</volume>
          <issue>6</issue>
          <fpage>M352</fpage>
          <lpage>M363</lpage>
        </element-citation>
        <mixed-citation>306. Aronow WS. Management of the older person with atrial fibrillation. J Gerontol A Biol Sci Med Sci. 2002;57(6):M352-63.</mixed-citation>
      </ref>
      <ref id="B307">
        <label>307</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Desai</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>El-Chami</surname>
              <given-names>MF</given-names>
            </name>
            <name>
              <surname>Leon</surname>
              <given-names>AR</given-names>
            </name>
            <name>
              <surname>Merchant</surname>
              <given-names>MF</given-names>
            </name>
          </person-group>
          <article-title>Management of atrial fibrillation in elderly adults</article-title>
          <source>J Am Geriatr Soc</source>
          <year>2017</year>
          <volume>65</volume>
          <issue>1</issue>
          <fpage>185</fpage>
          <lpage>193</lpage>
        </element-citation>
        <mixed-citation>307. Desai Y, El-Chami MF, Leon AR, Merchant MF. Management of atrial fibrillation in elderly adults. J Am Geriatr Soc. 2017;65(1):185-93.</mixed-citation>
      </ref>
      <ref id="B308">
        <label>308</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Patel</surname>
              <given-names>PA</given-names>
            </name>
            <name>
              <surname>Ali</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Hogarth</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Tayebjee</surname>
              <given-names>MH</given-names>
            </name>
          </person-group>
          <article-title>Management strategies for atrial fibrillation</article-title>
          <source>J R Soc Med</source>
          <year>2017</year>
          <volume>110</volume>
          <issue>1</issue>
          <fpage>13</fpage>
          <lpage>22</lpage>
        </element-citation>
        <mixed-citation>308. Patel PA, Ali N, Hogarth A, Tayebjee MH. Management strategies for atrial fibrillation. J R Soc Med. 2017;110(1):13-22.</mixed-citation>
      </ref>
      <ref id="B309">
        <label>309</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>van Gelder</surname>
              <given-names>IC</given-names>
            </name>
            <name>
              <surname>Rienstra</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Crijns</surname>
              <given-names>HJ</given-names>
            </name>
            <name>
              <surname>Olshansky</surname>
              <given-names>B</given-names>
            </name>
          </person-group>
          <article-title>Rate control in atrial fibrillation</article-title>
          <source>Lancet</source>
          <year>2016</year>
          <volume>388</volume>
          <issue>10046</issue>
          <fpage>818</fpage>
          <lpage>828</lpage>
        </element-citation>
        <mixed-citation>309. Van Gelder IC, Rienstra M, Crijns HJ, Olshansky B. Rate control in atrial fibrillation. Lancet. 2016;388(10046):818-28.</mixed-citation>
      </ref>
      <ref id="B310">
        <label>310</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Piccini</surname>
              <given-names>JP</given-names>
            </name>
            <name>
              <surname>Fauchier</surname>
              <given-names>L</given-names>
            </name>
          </person-group>
          <article-title>Rhythm control in atrial fibrillation</article-title>
          <source>Lancet</source>
          <year>2016</year>
          <volume>388</volume>
          <issue>10046</issue>
          <fpage>829</fpage>
          <lpage>840</lpage>
        </element-citation>
        <mixed-citation>310. Piccini JP, Fauchier L. Rhythm control in atrial fibrillation. Lancet. 2016;388(10046):829-40.</mixed-citation>
      </ref>
      <ref id="B311">
        <label>311</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Mulder</surname>
              <given-names>BA</given-names>
            </name>
            <name>
              <surname>van Veldhuisen</surname>
              <given-names>DJ</given-names>
            </name>
            <name>
              <surname>Crijns</surname>
              <given-names>HJ</given-names>
            </name>
            <name>
              <surname>Tijssen</surname>
              <given-names>JG</given-names>
            </name>
            <name>
              <surname>Hillege</surname>
              <given-names>HL</given-names>
            </name>
            <name>
              <surname>Hillege</surname>
              <given-names>HL</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>RACE II Investigators. Lenient vs. strict rate control in patients with atrial fibrillation and heart failure: a post-hoc analysis of the RACE II Study</article-title>
          <source>Eur J Heart Fail</source>
          <year>2013</year>
          <volume>15</volume>
          <issue>11</issue>
          <fpage>1311</fpage>
          <lpage>1318</lpage>
        </element-citation>
        <mixed-citation>311. Mulder BA, Van Veldhuisen DJ, Crijns HJ, Tijssen JG, Hillege HL, Hillege HL, et al; RACE II Investigators. Lenient vs. strict rate control in patients with atrial fibrillation and heart failure: a post-hoc analysis of the RACE II Study. Eur J Heart Fail. 2013;15(11):1311-8.</mixed-citation>
      </ref>
      <ref id="B312">
        <label>312</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>van Gelder</surname>
              <given-names>IC</given-names>
            </name>
            <name>
              <surname>Groenveld</surname>
              <given-names>HF</given-names>
            </name>
            <name>
              <surname>Crijns</surname>
              <given-names>HJ</given-names>
            </name>
            <name>
              <surname>Tuininga</surname>
              <given-names>YS</given-names>
            </name>
            <name>
              <surname>Tijssen</surname>
              <given-names>JG</given-names>
            </name>
            <name>
              <surname>Alings</surname>
              <given-names>AM</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>RACE II Investigators. Lenient versus strict rate control in patients with atrial fibrillation</article-title>
          <source>N Engl J Med</source>
          <year>2010</year>
          <volume>362</volume>
          <issue>15</issue>
          <fpage>1363</fpage>
          <lpage>1373</lpage>
        </element-citation>
        <mixed-citation>312. Van Gelder IC, Groenveld HF, Crijns HJ, Tuininga YS, Tijssen JG, Alings AM, et al; RACE II Investigators. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med. 2010;362(15):1363-73.</mixed-citation>
      </ref>
      <ref id="B313">
        <label>313</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Magalh&#227;es</surname>
              <given-names>LP</given-names>
            </name>
            <name>
              <surname>Figueiredo</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Cintra</surname>
              <given-names>FD</given-names>
            </name>
            <name>
              <surname>Saad</surname>
              <given-names>EB</given-names>
            </name>
            <name>
              <surname>Kuniyishi</surname>
              <given-names>RR</given-names>
            </name>
            <name>
              <surname>Teixeira</surname>
              <given-names>RA</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>II Diretrizes brasileiras de fibrila&#231;&#227;o atrial</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2016</year>
          <volume>106</volume>
          <supplement>4 Supl. 2</supplement>
          <fpage>1</fpage>
          <lpage>22</lpage>
        </element-citation>
        <mixed-citation>313. Magalh&#227;es LP, Figueiredo MJ, Cintra FD, Saad EB, Kuniyishi RR, Teixeira RA, et al. II Diretrizes brasileiras de fibrila&#231;&#227;o atrial. Arq Bras Cardiol. 2016;106 (4 Supl. 2):1-22.</mixed-citation>
      </ref>
      <ref id="B314">
        <label>314</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Marshall</surname>
              <given-names>HJ</given-names>
            </name>
            <name>
              <surname>Harris</surname>
              <given-names>ZI</given-names>
            </name>
            <name>
              <surname>Griffith</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Gammage</surname>
              <given-names>MD</given-names>
            </name>
          </person-group>
          <article-title>Atrioventricular nodal ablation and implantation of mode switching dual chamber pacemakers: effective treatment for drug refractory paroxysmal atrial fibrillation</article-title>
          <source>Heart</source>
          <year>1998</year>
          <volume>79</volume>
          <issue>6</issue>
          <fpage>543</fpage>
          <lpage>547</lpage>
        </element-citation>
        <mixed-citation>314. Marshall HJ, Harris ZI, Griffith MJ, Gammage MD. Atrioventricular nodal ablation and implantation of mode switching dual chamber pacemakers: effective treatment for drug refractory paroxysmal atrial fibrillation. Heart. 1998;79(6):543-7.</mixed-citation>
      </ref>
      <ref id="B315">
        <label>315</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ganesan</surname>
              <given-names>AN</given-names>
            </name>
            <name>
              <surname>Brooks</surname>
              <given-names>AG</given-names>
            </name>
            <name>
              <surname>Roberts-Thomson</surname>
              <given-names>KC</given-names>
            </name>
            <name>
              <surname>Lau</surname>
              <given-names>DH</given-names>
            </name>
            <name>
              <surname>Kalman</surname>
              <given-names>JM</given-names>
            </name>
            <name>
              <surname>Sanders</surname>
              <given-names>P</given-names>
            </name>
          </person-group>
          <article-title>Role of AV nodal ablation in cardiac resynchronization in patients with coexistent atrial fibrillation and heart failure: a systematic review</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2012</year>
          <volume>59</volume>
          <issue>8</issue>
          <fpage>719</fpage>
          <lpage>726</lpage>
        </element-citation>
        <mixed-citation>315. Ganesan AN, Brooks AG, Roberts-Thomson KC, Lau DH, Kalman JM, Sanders P. Role of AV nodal ablation in cardiac resynchronization in patients with coexistent atrial fibrillation and heart failure: a systematic review. J Am Coll Cardiol. 2012;59(8):719-26.</mixed-citation>
      </ref>
      <ref id="B316">
        <label>316</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Olshansky</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Rosenfeld</surname>
              <given-names>LE</given-names>
            </name>
            <name>
              <surname>Warner</surname>
              <given-names>AL</given-names>
            </name>
            <name>
              <surname>Solomon</surname>
              <given-names>AJ</given-names>
            </name>
            <name>
              <surname>O&#8217;Neill</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Sharma</surname>
              <given-names>A</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>AFFIRM Investigators. The atrial fibrillation follow-up investigation of rhythm management (AFFIRM) study: approaches to control rate in atrial fibrillation</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2004</year>
          <volume>43</volume>
          <issue>7</issue>
          <fpage>1201</fpage>
          <lpage>1208</lpage>
        </element-citation>
        <mixed-citation>316. Olshansky B, Rosenfeld LE, Warner AL, Solomon AJ, O&#8217;Neill G, Sharma A et al.; AFFIRM Investigators. The atrial fibrillation follow-up investigation of rhythm management (AFFIRM) study: approaches to control rate in atrial fibrillation. J Am Coll Cardiol. 2004;43(7):1201-8.</mixed-citation>
      </ref>
      <ref id="B317">
        <label>317</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>January</surname>
              <given-names>CT</given-names>
            </name>
            <name>
              <surname>Wann</surname>
              <given-names>LS</given-names>
            </name>
            <name>
              <surname>Alpert</surname>
              <given-names>JS</given-names>
            </name>
            <name>
              <surname>Calkins</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Cigarroa</surname>
              <given-names>JE</given-names>
            </name>
            <name>
              <surname>Cleveland</surname>
              <given-names>JC</given-names>
              <suffix>Jr</suffix>
            </name>
            <etal/>
          </person-group>
          <article-title>ACC/AHA Task Force Members. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: Executive Summary: a Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society</article-title>
          <source>Circulation</source>
          <year>2014</year>
          <volume>130</volume>
          <issue>23</issue>
          <fpage>2071</fpage>
          <lpage>2104</lpage>
        </element-citation>
        <mixed-citation>317. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr et al.; ACC/AHA Task Force Members. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: Executive Summary: a Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation. 2014;130(23):2071-104.</mixed-citation>
      </ref>
      <ref id="B318">
        <label>318</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Calkins</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Kuck</surname>
              <given-names>KH</given-names>
            </name>
            <name>
              <surname>Cappato</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Brugada</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Camm</surname>
              <given-names>AJ</given-names>
            </name>
            <name>
              <surname>Chen</surname>
              <given-names>SA</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. Developed in partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology (ESC) and the European Cardiac Arrhythmia Society (ECAS); and in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the Society of Thoracic Surgeons (STS). Endorsed by the governing bodies of the American College of Cardiology Foundation, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, the Asia Pacific Heart Rhythm Society, and the Heart Rhythm Society</article-title>
          <source>Heart Rhythm</source>
          <year>2012</year>
          <volume>9</volume>
          <issue>4</issue>
          <fpage>632</fpage>
          <lpage>696</lpage>
        </element-citation>
        <mixed-citation>318. Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA et al. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. Developed in partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology (ESC) and the European Cardiac Arrhythmia Society (ECAS); and in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the Society of Thoracic Surgeons (STS). Endorsed by the governing bodies of the American College of Cardiology Foundation, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, the Asia Pacific Heart Rhythm Society, and the Heart Rhythm Society. Heart Rhythm. 2012;9(4):632-96.</mixed-citation>
      </ref>
      <ref id="B319">
        <label>319</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Lip</surname>
              <given-names>GY</given-names>
            </name>
            <name>
              <surname>Skj&#248;th</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Nielsen</surname>
              <given-names>PB</given-names>
            </name>
            <name>
              <surname>Larsen</surname>
              <given-names>TB</given-names>
            </name>
          </person-group>
          <article-title>Non-valvular atrial fibrillation patients with none or one additional risk factor of the CHA2DS2-VASc score. A comprehensive net clinical benefit analysis for warfarin, aspirin, or no therapy</article-title>
          <source>Thromb Haemost</source>
          <year>2015</year>
          <volume>114</volume>
          <issue>4</issue>
          <fpage>826</fpage>
          <lpage>834</lpage>
        </element-citation>
        <mixed-citation>319. Lip GY, Skj&#248;th F, Nielsen PB, Larsen TB. Non-valvular atrial fibrillation patients with none or one additional risk factor of the CHA2DS2-VASc score. A comprehensive net clinical benefit analysis for warfarin, aspirin, or no therapy. Thromb Haemost. 2015;114(4):826-34.</mixed-citation>
      </ref>
      <ref id="B320">
        <label>320</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Hart</surname>
              <given-names>RG</given-names>
            </name>
            <name>
              <surname>Pearce</surname>
              <given-names>LA</given-names>
            </name>
            <name>
              <surname>Aguilar</surname>
              <given-names>MI</given-names>
            </name>
          </person-group>
          <article-title>Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation</article-title>
          <source>Ann Intern Med</source>
          <year>2007</year>
          <volume>146</volume>
          <issue>12</issue>
          <fpage>857</fpage>
          <lpage>867</lpage>
        </element-citation>
        <mixed-citation>320. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146(12):857-67.</mixed-citation>
      </ref>
      <ref id="B321">
        <label>321</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Connolly</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Pogue</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Hart</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Pfeffer</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Hohnloser</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Chrolavicius</surname>
              <given-names>S</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>ACTIVE Writing Group of the ACTIVE Investigators. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial</article-title>
          <source>Lancet</source>
          <year>2006</year>
          <volume>367</volume>
          <issue>9526</issue>
          <fpage>1903</fpage>
          <lpage>1912</lpage>
        </element-citation>
        <mixed-citation>321. Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, Chrolavicius S et al.; ACTIVE Writing Group of the ACTIVE Investigators. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet. 2006;367(9526):1903-12.</mixed-citation>
      </ref>
      <ref id="B322">
        <label>322</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Piccini</surname>
              <given-names>JP</given-names>
            </name>
            <name>
              <surname>Hammill</surname>
              <given-names>BG</given-names>
            </name>
            <name>
              <surname>Sinner</surname>
              <given-names>MF</given-names>
            </name>
            <name>
              <surname>Jensen</surname>
              <given-names>PN</given-names>
            </name>
            <name>
              <surname>Hernandez</surname>
              <given-names>AF</given-names>
            </name>
            <name>
              <surname>Heckbert</surname>
              <given-names>SR</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Incidence and prevalence of atrial fibrillation and associated mortality among Medicare beneficiaries: 1993-2007</article-title>
          <source>Circ Cardiovasc Qual Outcomes</source>
          <year>2012</year>
          <volume>5</volume>
          <issue>1</issue>
          <fpage>85</fpage>
          <lpage>93</lpage>
        </element-citation>
        <mixed-citation>322. Piccini JP, Hammill BG, Sinner MF, Jensen PN, Hernandez AF, Heckbert SR et al. Incidence and prevalence of atrial fibrillation and associated mortality among Medicare beneficiaries: 1993-2007. Circ Cardiovasc Qual Outcomes. 2012;5(1):85-93.</mixed-citation>
      </ref>
      <ref id="B323">
        <label>323</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Gage</surname>
              <given-names>BF</given-names>
            </name>
            <name>
              <surname>Waterman</surname>
              <given-names>AD</given-names>
            </name>
            <name>
              <surname>Shannon</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>Boechler</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Rich</surname>
              <given-names>MW</given-names>
            </name>
            <name>
              <surname>Radford</surname>
              <given-names>MJ</given-names>
            </name>
          </person-group>
          <article-title>Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation</article-title>
          <source>JAMA</source>
          <year>2001</year>
          <volume>285</volume>
          <issue>22</issue>
          <fpage>2864</fpage>
          <lpage>2870</lpage>
        </element-citation>
        <mixed-citation>323. Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA. 2001;285(22):2864-70.</mixed-citation>
      </ref>
      <ref id="B324">
        <label>324</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Steffel</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Verhamme</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Potpara</surname>
              <given-names>TS</given-names>
            </name>
            <name>
              <surname>Albaladejo</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Antz</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Desteghe</surname>
              <given-names>L</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>ESC Scientific Document Group. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation</article-title>
          <source>European Heart Journal</source>
          <year>2018</year>
          <volume>39</volume>
          <issue>16</issue>
          <fpage>1330</fpage>
          <lpage>1393</lpage>
        </element-citation>
        <mixed-citation>324. Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L et al. ESC Scientific Document Group. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. European Heart Journal. 2018;39(16):1330-1393.</mixed-citation>
      </ref>
      <ref id="B325">
        <label>325</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>January</surname>
              <given-names>CT</given-names>
            </name>
            <name>
              <surname>Wann</surname>
              <given-names>LS</given-names>
            </name>
            <name>
              <surname>Calkins</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Field</surname>
              <given-names>ME</given-names>
            </name>
            <name>
              <surname>Chen</surname>
              <given-names>LY</given-names>
            </name>
            <name>
              <surname>Furie</surname>
              <given-names>KL</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation</article-title>
          <source>Heart Rhythm</source>
          <year>2019</year>
        </element-citation>
        <mixed-citation>325. January CT, Wann LS, Calkins H, Field ME, Chen LY, Furie KL et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. Heart Rhythm. 2019.</mixed-citation>
      </ref>
      <ref id="B326">
        <label>326</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Lee</surname>
              <given-names>JM</given-names>
            </name>
            <name>
              <surname>Shim</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Uhm</surname>
              <given-names>JS</given-names>
            </name>
            <name>
              <surname>Kim</surname>
              <given-names>YJ</given-names>
            </name>
            <name>
              <surname>Lee</surname>
              <given-names>HJ</given-names>
            </name>
            <name>
              <surname>Pak</surname>
              <given-names>HN</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Impact of increased orifice size and decreased flow velocity of left atrial appendage on stroke in nonvalvular atrial fibrillation</article-title>
          <source>Am J Cardiol</source>
          <year>2014</year>
          <volume>113</volume>
          <issue>6</issue>
          <fpage>963</fpage>
          <lpage>969</lpage>
        </element-citation>
        <mixed-citation>326. Lee JM, Shim J, Uhm JS, Kim YJ, Lee HJ, Pak HN et al. Impact of increased orifice size and decreased flow velocity of left atrial appendage on stroke in nonvalvular atrial fibrillation. Am J Cardiol. 2014;113(6):963-9.</mixed-citation>
      </ref>
      <ref id="B327">
        <label>327</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Gupta</surname>
              <given-names>DK</given-names>
            </name>
            <name>
              <surname>Shah</surname>
              <given-names>AM</given-names>
            </name>
            <name>
              <surname>Giugliano</surname>
              <given-names>RP</given-names>
            </name>
            <name>
              <surname>Ruff</surname>
              <given-names>CT</given-names>
            </name>
            <name>
              <surname>Antman</surname>
              <given-names>EM</given-names>
            </name>
            <name>
              <surname>Grip</surname>
              <given-names>LT</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Effective aNticoaGulation with factor xA next GEneration in AF-Thrombolysis In Myocardial Infarction 48 Echocardiographic Study Investigators. Left atrial structure and function in atrial fibrillation: ENGAGE AF-TIMI 48</article-title>
          <source>Eur Heart J</source>
          <year>2014</year>
          <volume>35</volume>
          <issue>22</issue>
          <fpage>1457</fpage>
          <lpage>1465</lpage>
        </element-citation>
        <mixed-citation>327. Gupta DK, Shah AM, Giugliano RP, Ruff CT, Antman EM, Grip LT et al.; Effective aNticoaGulation with factor xA next GEneration in AF-Thrombolysis In Myocardial Infarction 48 Echocardiographic Study Investigators. Left atrial structure and function in atrial fibrillation: ENGAGE AF-TIMI 48. Eur Heart J. 2014;35(22):1457-65.</mixed-citation>
      </ref>
      <ref id="B328">
        <label>328</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Lip</surname>
              <given-names>GY</given-names>
            </name>
          </person-group>
          <article-title>Stroke and bleeding risk assessment in atrial fibrillation: when, how, and why?</article-title>
          <source>Eur Heart J</source>
          <year>2013</year>
          <volume>34</volume>
          <issue>14</issue>
          <fpage>1041</fpage>
          <lpage>1049</lpage>
        </element-citation>
        <mixed-citation>328. Lip GY. Stroke and bleeding risk assessment in atrial fibrillation: when, how, and why? Eur Heart J. 2013;34(14):1041-9.</mixed-citation>
      </ref>
      <ref id="B329">
        <label>329</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ansell</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Hirsh</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Dalen</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Bussey</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Anderson</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Poller</surname>
              <given-names>L</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Managing oral anticoagulant therapy</article-title>
          <source>Chest</source>
          <year>2001</year>
          <volume>119</volume>
          <supplement>1 Suppl</supplement>
          <fpage>22S</fpage>
          <lpage>38S</lpage>
        </element-citation>
        <mixed-citation>329. Ansell J, Hirsh J, Dalen D, Bussey H, Anderson D, Poller L et al. Managing oral anticoagulant therapy. Chest. 2001;119(1 Suppl):22S-38S.</mixed-citation>
      </ref>
      <ref id="B330">
        <label>330</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ruff</surname>
              <given-names>CT</given-names>
            </name>
            <name>
              <surname>Giugliano</surname>
              <given-names>RP</given-names>
            </name>
            <name>
              <surname>Braunwald</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Hoffman</surname>
              <given-names>EB</given-names>
            </name>
            <name>
              <surname>Deenadayalu</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Ezekowitz</surname>
              <given-names>MD</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials</article-title>
          <source>Lancet</source>
          <year>2014</year>
          <volume>383</volume>
          <issue>9921</issue>
          <fpage>955</fpage>
          <lpage>962</lpage>
        </element-citation>
        <mixed-citation>330. Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955-62.</mixed-citation>
      </ref>
      <ref id="B331">
        <label>331</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Sharma</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Cornelius</surname>
              <given-names>VR</given-names>
            </name>
            <name>
              <surname>Patel</surname>
              <given-names>JP</given-names>
            </name>
            <name>
              <surname>Davies</surname>
              <given-names>JG</given-names>
            </name>
            <name>
              <surname>Molokhia</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
          <article-title>Efficacy and harms of direct oral anticoagulants in the elderly for stroke prevention in atrial fibrillation and secondary prevention of venous thromboembolism: systematic review and meta-analysis</article-title>
          <source>Circulation</source>
          <year>2015</year>
          <volume>132</volume>
          <issue>3</issue>
          <fpage>194</fpage>
          <lpage>204</lpage>
        </element-citation>
        <mixed-citation>331. Sharma M, Cornelius VR, Patel JP, Davies JG, Molokhia M. Efficacy and harms of direct oral anticoagulants in the elderly for stroke prevention in atrial fibrillation and secondary prevention of venous thromboembolism: systematic review and meta-analysis. Circulation. 2015;132(3):194-204.</mixed-citation>
      </ref>
      <ref id="B332">
        <label>332</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Pollack</surname>
              <given-names>CV</given-names>
              <suffix>Jr</suffix>
            </name>
            <name>
              <surname>Reilly</surname>
              <given-names>PA</given-names>
            </name>
            <name>
              <surname>Eikelboom</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Glund</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Verhamme</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Bernstein</surname>
              <given-names>RA</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Idarucizumab for dabigatran reversal</article-title>
          <source>N Engl J Med</source>
          <year>2015</year>
          <volume>373</volume>
          <issue>6</issue>
          <fpage>511</fpage>
          <lpage>520</lpage>
        </element-citation>
        <mixed-citation>332. Pollack CV Jr, Reilly PA, Eikelboom J, Glund S, Verhamme P, Bernstein RA et al. Idarucizumab for dabigatran reversal. N Engl J Med. 2015;373(6):511-20.</mixed-citation>
      </ref>
    </ref-list>
  </back>
  <sub-article article-type="translation" id="S01" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Updated</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Updated Geriatric Cardiology Guidelines of the Brazilian Society of Cardiology &#8211; 2019</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Feitosa</surname>
            <given-names>Gilson Soares</given-names>
            <suffix>Filho</suffix>
          </name>
          <xref ref-type="aff" rid="aff45">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Peixoto</surname>
            <given-names>Jos&#233; Maria</given-names>
          </name>
          <xref ref-type="aff" rid="aff46">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pinheiro</surname>
            <given-names>Jos&#233; Elias Soares</given-names>
          </name>
          <xref ref-type="aff" rid="aff47">
            <sup>3</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Afiune</surname>
            <given-names>Abrah&#227;o</given-names>
            <suffix>Neto</suffix>
          </name>
          <xref ref-type="aff" rid="aff48">
            <sup>4</sup>
          </xref>
          <xref ref-type="aff" rid="aff49">
            <sup>5</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Albuquerque</surname>
            <given-names>Afonso Luiz Tavares de</given-names>
          </name>
          <xref ref-type="aff" rid="aff50">
            <sup>6</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Cattani</surname>
            <given-names>&#193;lvaro C&#233;sar</given-names>
          </name>
          <xref ref-type="aff" rid="aff51">
            <sup>7</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nussbacher</surname>
            <given-names>Amit</given-names>
          </name>
          <xref ref-type="aff" rid="aff52">
            <sup>8</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Camarano</surname>
            <given-names>Ana Amelia</given-names>
          </name>
          <xref ref-type="aff" rid="aff53">
            <sup>9</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Sichinels</surname>
            <given-names>Angela Herm&#237;nia</given-names>
          </name>
          <xref ref-type="aff" rid="aff54">
            <sup>10</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Sousa</surname>
            <given-names>Antonio Carlos Sobral</given-names>
          </name>
          <xref ref-type="aff" rid="aff55">
            <sup>11</sup>
          </xref>
          <xref ref-type="aff" rid="aff56">
            <sup>12</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Alencar</surname>
            <given-names>Arist&#243;teles Comte de Alencar</given-names>
            <suffix>Filho</suffix>
          </name>
          <xref ref-type="aff" rid="aff57">
            <sup>13</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gravina</surname>
            <given-names>Claudia F.</given-names>
          </name>
          <xref ref-type="aff" rid="aff58">
            <sup>14</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Sobral</surname>
            <given-names>Dario Celestino</given-names>
            <suffix>Filho</suffix>
          </name>
          <xref ref-type="aff" rid="aff50">
            <sup>6</sup>
          </xref>
          <xref ref-type="aff" rid="aff59">
            <sup>15</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pitthan</surname>
            <given-names>Eduardo</given-names>
          </name>
          <xref ref-type="aff" rid="aff60">
            <sup>16</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Costa</surname>
            <given-names>Elisa Franco de Assis</given-names>
          </name>
          <xref ref-type="aff" rid="aff47">
            <sup>3</sup>
          </xref>
          <xref ref-type="aff" rid="aff48">
            <sup>4</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Duarte</surname>
            <given-names>Elizabeth da Rosa</given-names>
          </name>
          <xref ref-type="aff" rid="aff61">
            <sup>17</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Freitas</surname>
            <given-names>Elizabete Viana de</given-names>
          </name>
          <xref ref-type="aff" rid="aff62">
            <sup>18</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Moriguchi</surname>
            <given-names>Emilio Hideyuki</given-names>
          </name>
          <xref ref-type="aff" rid="aff63">
            <sup>19</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mesquita</surname>
            <given-names>Evandro Tinoco</given-names>
          </name>
          <xref ref-type="aff" rid="aff64">
            <sup>20</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Fernandes</surname>
            <given-names>F&#225;bio</given-names>
          </name>
          <xref ref-type="aff" rid="aff65">
            <sup>21</sup>
          </xref>
          <xref ref-type="aff" rid="aff66">
            <sup>22</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Fuchs</surname>
            <given-names>Felipe Costa</given-names>
          </name>
          <xref ref-type="aff" rid="aff63">
            <sup>19</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Feitosa</surname>
            <given-names>Gilson Soares</given-names>
          </name>
          <xref ref-type="aff" rid="aff45">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pierre</surname>
            <given-names>Humberto</given-names>
          </name>
          <xref ref-type="aff" rid="aff67">
            <sup>23</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pereira</surname>
            <given-names>Ilnei</given-names>
            <suffix>Filho</suffix>
          </name>
          <xref ref-type="aff" rid="aff68">
            <sup>24</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Helber</surname>
            <given-names>Izo</given-names>
          </name>
          <xref ref-type="aff" rid="aff67">
            <sup>23</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Borges</surname>
            <given-names>Jairo Lins</given-names>
          </name>
          <xref ref-type="aff" rid="aff67">
            <sup>23</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Garcia</surname>
            <given-names>J&#233;ssica Myrian de Amorim</given-names>
          </name>
          <xref ref-type="aff" rid="aff69">
            <sup>25</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Souza</surname>
            <given-names>Jos&#233; Antonio Gordillo de</given-names>
          </name>
          <xref ref-type="aff" rid="aff70">
            <sup>26</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Zanon</surname>
            <given-names>Jos&#233; Carlos da Costa</given-names>
          </name>
          <xref ref-type="aff" rid="aff71">
            <sup>27</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Alves</surname>
            <given-names>Josmar de Castro</given-names>
          </name>
          <xref ref-type="aff" rid="aff72">
            <sup>28</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mohallem</surname>
            <given-names>Kalil Lays</given-names>
          </name>
          <xref ref-type="aff" rid="aff73">
            <sup>29</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Chaves</surname>
            <given-names>Laura Mariana de Siqueira Mendon&#231;a</given-names>
          </name>
          <xref ref-type="aff" rid="aff69">
            <sup>25</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Moura</surname>
            <given-names>L&#237;dia Ana Zytynski</given-names>
          </name>
          <xref ref-type="aff" rid="aff74">
            <sup>30</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Silva</surname>
            <given-names>M&#225;rcia Cristina Am&#233;lia da</given-names>
          </name>
          <xref ref-type="aff" rid="aff50">
            <sup>6</sup>
          </xref>
          <xref ref-type="aff" rid="aff59">
            <sup>15</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Toledo</surname>
            <given-names>Maria Alice de Vilhena</given-names>
          </name>
          <xref ref-type="aff" rid="aff75">
            <sup>31</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Assun&#231;&#227;o</surname>
            <given-names>Maria Elisa Lucena Sales de Melo</given-names>
          </name>
          <xref ref-type="aff" rid="aff50">
            <sup>6</sup>
          </xref>
          <xref ref-type="aff" rid="aff59">
            <sup>15</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Wajngarten</surname>
            <given-names>Mauricio</given-names>
          </name>
          <xref ref-type="aff" rid="aff76">
            <sup>32</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gon&#231;alves</surname>
            <given-names>Mauro Jos&#233; Oliveira</given-names>
          </name>
          <xref ref-type="aff" rid="aff77">
            <sup>33</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lopes</surname>
            <given-names>Neuza Helena Moreira</given-names>
          </name>
          <xref ref-type="aff" rid="aff65">
            <sup>21</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rodrigues</surname>
            <given-names>Nezilour Lobato</given-names>
          </name>
          <xref ref-type="aff" rid="aff78">
            <sup>34</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Toscano</surname>
            <given-names>Paulo Roberto Pereira</given-names>
          </name>
          <xref ref-type="aff" rid="aff79">
            <sup>35</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rousseff</surname>
            <given-names>Pedro</given-names>
          </name>
          <xref ref-type="aff" rid="aff80">
            <sup>36</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Maia</surname>
            <given-names>Ricardo Antonio Rosado</given-names>
          </name>
          <xref ref-type="aff" rid="aff81">
            <sup>37</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Franken</surname>
            <given-names>Roberto Alexandre</given-names>
          </name>
          <xref ref-type="aff" rid="aff82">
            <sup>38</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Miranda</surname>
            <given-names>Roberto Dischinger</given-names>
          </name>
          <xref ref-type="aff" rid="aff67">
            <sup>23</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gamarski</surname>
            <given-names>Roberto</given-names>
          </name>
          <xref ref-type="aff" rid="aff83">
            <sup>39</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rosa</surname>
            <given-names>Ronaldo Fernandes</given-names>
          </name>
          <xref ref-type="aff" rid="aff82">
            <sup>38</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Santos</surname>
            <given-names>Silvio Carlos de Moraes</given-names>
          </name>
          <xref ref-type="aff" rid="aff84">
            <sup>40</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Galera</surname>
            <given-names>Siulmara Cristina</given-names>
          </name>
          <xref ref-type="aff" rid="aff85">
            <sup>41</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Grespan</surname>
            <given-names>Stela Maris da Silva</given-names>
          </name>
          <xref ref-type="aff" rid="aff67">
            <sup>23</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Silva</surname>
            <given-names>Teresa Cristina Rogerio da</given-names>
          </name>
          <xref ref-type="aff" rid="aff45">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Esteves</surname>
            <given-names>William Antonio de Magalh&#227;es</given-names>
          </name>
          <xref ref-type="aff" rid="aff86">
            <sup>42</sup>
          </xref>
          <xref ref-type="aff" rid="aff87">
            <sup>43</sup>
          </xref>
          <xref ref-type="aff" rid="aff88">
            <sup>44</sup>
          </xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <aff id="aff45">
          <label>1</label>
          <addr-line>
            <named-content content-type="city">Salvador</named-content>
            <named-content content-type="state">BA</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Escola Bahiana de Medicina e Sa&#250;de P&#250;blica, Salvador, BA &#8211; Brazil</institution>
        </aff>
        <aff id="aff46">
          <label>2</label>
          <addr-line>
            <named-content content-type="city">Belo Horizonte</named-content>
            <named-content content-type="state">MG</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade Jos&#233; do Ros&#225;rio Vellano (UNIFENAS), Belo Horizonte, MG &#8211; Brazil</institution>
        </aff>
        <aff id="aff47">
          <label>3</label>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Sociedade Brasileira de Geriatria e Gerontologia (SBGG), Rio de Janeiro, RJ &#8211; Brazil</institution>
        </aff>
        <aff id="aff48">
          <label>4</label>
          <addr-line>
            <named-content content-type="city">Goi&#226;nia</named-content>
            <named-content content-type="state">GO</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade Federal de Goi&#225;s (UFG), Goi&#226;nia, GO &#8211; Brazil</institution>
        </aff>
        <aff id="aff49">
          <label>5</label>
          <addr-line>
            <named-content content-type="city">An&#225;polis</named-content>
            <named-content content-type="state">GO</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">UniEVANG&#201;LICA, An&#225;polis, GO &#8211; Brazil</institution>
        </aff>
        <aff id="aff50">
          <label>6</label>
          <addr-line>
            <named-content content-type="city">Recife</named-content>
            <named-content content-type="state">PE</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade de Pernambuco (UPE), Recife, PE &#8211; Brazil</institution>
        </aff>
        <aff id="aff51">
          <label>7</label>
          <addr-line>
            <named-content content-type="city">Pato Branco</named-content>
            <named-content content-type="state">PR</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Hospital S&#227;o Lucas, Pato Branco, PR &#8211; Brazil</institution>
        </aff>
        <aff id="aff52">
          <label>8</label>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade de S&#227;o Paulo (USP), S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff53">
          <label>9</label>
          <addr-line>
            <named-content content-type="city">Bras&#237;lia</named-content>
            <named-content content-type="state">DF</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Instituto de Pesquisa Econ&#244;mica Aplicada (IPEA), Bras&#237;lia, DF &#8211; Brazil</institution>
        </aff>
        <aff id="aff54">
          <label>10</label>
          <addr-line>
            <named-content content-type="city">Campo Grande</named-content>
            <named-content content-type="state">MS</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Hospital S&#227;o Juli&#227;o, Campo Grande, MS &#8211; Brazil</institution>
        </aff>
        <aff id="aff55">
          <label>11</label>
          <addr-line>
            <named-content content-type="city">Aracaju</named-content>
            <named-content content-type="state">SE</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade Federal de Sergipe (UFS), Aracaju, SE &#8211; Brazil</institution>
        </aff>
        <aff id="aff56">
          <label>12</label>
          <addr-line>
            <named-content content-type="city">Aracaju</named-content>
            <named-content content-type="state">SE</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Hospital S&#227;o Lucas, Aracaju, SE &#8211; Brazil</institution>
        </aff>
        <aff id="aff57">
          <label>13</label>
          <addr-line>
            <named-content content-type="city">Manaus</named-content>
            <named-content content-type="state">AM</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade Federal do Amazonas (UFAM), Manaus, AM &#8211; Brazil</institution>
        </aff>
        <aff id="aff58">
          <label>14</label>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Instituto Dante Pazzanese de Cardiologia, S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff59">
          <label>15</label>
          <addr-line>
            <named-content content-type="city">Recife</named-content>
            <named-content content-type="state">PE</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Pronto-Socorro Cardiol&#243;gico Universit&#225;rio de Pernambuco (PROCAPE), Recife, PE &#8211; Brazil</institution>
        </aff>
        <aff id="aff60">
          <label>16</label>
          <addr-line>
            <named-content content-type="city">Chapec&#243;</named-content>
            <named-content content-type="state">SC</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade Federal da Fronteira Sul (UFFS), Chapec&#243;, SC &#8211; Brazil</institution>
        </aff>
        <aff id="aff61">
          <label>17</label>
          <addr-line>
            <named-content content-type="city">Tubar&#227;o</named-content>
            <named-content content-type="state">SC</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Hospital Nossa Senhora da Concei&#231;&#227;o (HNSC), Tubar&#227;o, SC &#8211; Brazil</institution>
        </aff>
        <aff id="aff62">
          <label>18</label>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ &#8211; Brazil</institution>
        </aff>
        <aff id="aff63">
          <label>19</label>
          <addr-line>
            <named-content content-type="city">Porto Alegre</named-content>
            <named-content content-type="state">RS</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade Federal do Rio Grande do Sul (UFRS), Porto Alegre, RS &#8211; Brazil</institution>
        </aff>
        <aff id="aff64">
          <label>20</label>
          <addr-line>
            <named-content content-type="city">Niter&#243;i</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade Federal Fluminense (UFF), Niter&#243;i, RJ &#8211; Brazil</institution>
        </aff>
        <aff id="aff65">
          <label>21</label>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Instituto do Cora&#231;&#227;o (Incor) da Faculdade de Medicina da Universidade de S&#227;o Paulo (FMUSP), S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff66">
          <label>22</label>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Departamento de Insufici&#234;ncia Card&#237;aca (DEIC) da Sociedade Brasileira de Cardiologia (SBC), Rio de Janeiro, RJ &#8211; Brazil</institution>
        </aff>
        <aff id="aff67">
          <label>23</label>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade Federal de S&#227;o Paulo (UNIFESP), S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff68">
          <label>24</label>
          <addr-line>
            <named-content content-type="city">S&#227;o Jos&#233;</named-content>
            <named-content content-type="state">SC</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Instituto de Cardiologia de Santa Catarina (ICSC), S&#227;o Jos&#233;, SC &#8211; Brazil</institution>
        </aff>
        <aff id="aff69">
          <label>25</label>
          <addr-line>
            <named-content content-type="city">Recife</named-content>
            <named-content content-type="state">PE</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Hospital Agamenon Magalh&#227;es, Recife, PE &#8211; Brazil</institution>
        </aff>
        <aff id="aff70">
          <label>26</label>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Sanofi, S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff71">
          <label>27</label>
          <addr-line>
            <named-content content-type="city">Ouro Preto</named-content>
            <named-content content-type="state">MG</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade Federal de Ouro Preto (UFOP), Ouro Preto, MG &#8211; Brazil</institution>
        </aff>
        <aff id="aff72">
          <label>28</label>
          <addr-line>
            <named-content content-type="city">Natal</named-content>
            <named-content content-type="state">RN</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Procardio Cl&#237;nica Cardiol&#243;gica, Natal, RN &#8211; Brazil</institution>
        </aff>
        <aff id="aff73">
          <label>29</label>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Hospital Pr&#243;-Card&#237;aco, Rio de Janeiro, RJ &#8211; Brazil</institution>
        </aff>
        <aff id="aff74">
          <label>30</label>
          <addr-line>
            <named-content content-type="city">Curitiba</named-content>
            <named-content content-type="state">PR</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Pontif&#237;cia Universidade Cat&#243;lica do Paran&#225; (PUC-PR), Curitiba, PR &#8211; Brazil</institution>
        </aff>
        <aff id="aff75">
          <label>31</label>
          <addr-line>
            <named-content content-type="city">Bras&#237;lia</named-content>
            <named-content content-type="state">DF</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade de Bras&#237;lia (UnB), Bras&#237;lia, DF &#8211; Brazil</institution>
        </aff>
        <aff id="aff76">
          <label>32</label>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Hospital Israelita Albert Einstein, S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff77">
          <label>33</label>
          <addr-line>
            <named-content content-type="city">Teresina</named-content>
            <named-content content-type="state">PI</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Hospital S&#227;o Marcos, Teresina, PI &#8211; Brazil</institution>
        </aff>
        <aff id="aff78">
          <label>34</label>
          <addr-line>
            <named-content content-type="city">Bel&#233;m</named-content>
            <named-content content-type="state">PA</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Hospital Universit&#225;rio Jo&#227;o de Barros Barreto, Bel&#233;m, PA &#8211; Brazil</institution>
        </aff>
        <aff id="aff79">
          <label>35</label>
          <addr-line>
            <named-content content-type="city">Bel&#233;m</named-content>
            <named-content content-type="state">PA</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade do Estado do Par&#225; (UEPA), Bel&#233;m, PA &#8211; Brazil</institution>
        </aff>
        <aff id="aff80">
          <label>36</label>
          <addr-line>
            <named-content content-type="city">Belo Horizontem</named-content>
            <named-content content-type="state">MG</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Hospital Madre Teresa, Belo Horizonte, MG &#8211; Brazil</institution>
        </aff>
        <aff id="aff81">
          <label>37</label>
          <addr-line>
            <named-content content-type="city">Jo&#227;o Pessoa</named-content>
            <named-content content-type="state">PB</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade Federal da Para&#237;ba (UFPB), Jo&#227;o Pessoa, PB &#8211; Brazil</institution>
        </aff>
        <aff id="aff82">
          <label>38</label>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Faculdade de Ci&#234;ncias M&#233;dicas da Santa Casa de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff83">
          <label>39</label>
          <addr-line>
            <named-content content-type="city">Rio de Janeiro</named-content>
            <named-content content-type="state">RJ</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ &#8211; Brazil</institution>
        </aff>
        <aff id="aff84">
          <label>40</label>
          <addr-line>
            <named-content content-type="city">Santos</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Instituto de An&#225;lises Cl&#237;nicas de Santos (IACS), Santos, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff85">
          <label>41</label>
          <addr-line>
            <named-content content-type="city">Fortaleza</named-content>
            <named-content content-type="state">CE</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade de Fortaleza (UniFor), Fortaleza, CE &#8211; Brazil</institution>
        </aff>
        <aff id="aff86">
          <label>42</label>
          <addr-line>
            <named-content content-type="city">Belo Horizonte</named-content>
            <named-content content-type="state">MG</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Hospital Vera Cruz, Belo Horizonte, MG &#8211; Brazil</institution>
        </aff>
        <aff id="aff87">
          <label>43</label>
          <addr-line>
            <named-content content-type="city">Belo Horizonte</named-content>
            <named-content content-type="state">MG</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Hospital das Cl&#237;nicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG &#8211; Brazil</institution>
        </aff>
        <aff id="aff88">
          <label>44</label>
          <addr-line>
            <named-content content-type="city">Ita&#250;na</named-content>
            <named-content content-type="state">MG</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade de Ita&#250;na, Ita&#250;na, MG &#8211; Brazil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><bold>Corresponding Address:</bold> Sociedade Brasileira de Cardiologia &#8211; Av. Marechal C&#226;mara, 360/330 &#8211; Centro &#8211; Rio de Janeiro &#8211; Postal Code: <postal-code>20020-907</postal-code>. E-mail: <email>sbc@cardiol.br</email></corresp>
      </author-notes>
    </front-stub>
    <body>
      <table-wrap id="t45">
        <table frame="hsides" rules="groups">
          <colgroup width="14%">
            <col/>
            <col/>
            <col/>
            <col/>
            <col/>
            <col/>
            <col/>
            <col/>
          </colgroup>
          <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
            <tr>
              <th align="left" valign="top" colspan="8">Declaration of potential conflict of interest of authors/collaborators of Updated Geriatric Cardiology Guidelines of the Brazilian Society of Cardiology &#8211; 2019 If the last three years the author/developer of the Updated:</th>
            </tr>
            <tr>
              <th align="left" valign="top">Names Members of the Policy</th>
              <th align="center" valign="top">Participated in clinical studies and/or experimental trials supported by pharmaceutical or equipment related to the guideline in question</th>
              <th align="center" valign="top">Has spoken at events or activities sponsored by industry related to the guideline in question</th>
              <th align="center" valign="top">It was (is) advisory board member or director of a pharmaceutical or equipment</th>
              <th align="center" valign="top">Committees participated in completion of research sponsored by industry</th>
              <th align="center" valign="top">Personal or institutional aid received from industry</th>
              <th align="center" valign="top">Produced scientific papers in journals sponsored by industry</th>
              <th align="center" valign="top">It shares the industry</th>
            </tr>
          </thead>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr>
              <td align="left" valign="top">Abrah&#227;o Afiune Neto</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Afonso Luiz Tavares de Albuquerque</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">&#193;lvaro C&#233;sar Cattani</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Amit Nussbacher</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Ana Amelia Camarano</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Angela Herm&#237;nia Sichinels</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Antonio Carlos Sobral Sousa</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">Bayer, Ach&#233;, Pfizer</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Arist&#243;teles Comte de Alencar Filho</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Claudia F. Gravina</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Dario Celestino Sobral Filho</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">Libbs</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Eduardo Pitthan</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Elisa Franco de Assis Costa</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">Abbott, Nutrition</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">Abbott, Nutrition</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Elizabeth da Rosa Duarte</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">Torrent, Bayer, Ache, EMS</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Elizabete Viana de Freitas</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Emilio Hideyuki Moriguchi</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Evandro Tinoco Mesquita</td>
              <td align="center" valign="top">Novartis, Servier</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">F&#225;bio Fernandes</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">Pfizer</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Felipe Costa Fuchs</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Gilson Soares Feitosa</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Gilson Soares Feitosa-Filho</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Humberto Pierre</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Ilnei Pereira Filho</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Izo Helber</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Jairo Lins Borges</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">LIBBS Farmac&#234;utica</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">LIBBS Farmac&#234;utica</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">J&#233;ssica Myrian de Amorim Garcia</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">Pfizer</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Jos&#233; Antonio Gordillo de Souza</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">Sanofi</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Jos&#233; Carlos da Costa Zanon</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Jos&#233; Elias Soares Pinheiro</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Jos&#233; Maria Peixoto</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Josmar de Castro Alves</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Kalil Lays Mohallem</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Laura Mariana de Siqueira Mendon&#231;a Chaves</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">L&#237;dia Ana Zytynski Moura</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">M&#225;rcia Cristina Am&#233;lia da Silva</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Maria Alice de Vilhena Toledo</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Maria Elisa Lucena Sales de Melo Assun&#231;&#227;o</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Mauricio Wajngarten</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Mauro Jos&#233; Oliveira Gon&#231;alves</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Neuza Helena Moreira Lopes</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Nezilour Lobato Rodrigues</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Paulo Roberto Pereira Toscano</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Pedro Rousseff</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Ricardo Antonio Rosado Maia</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Roberto Alexandre Franken</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Roberto Dischinger Miranda</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">Ach&#233;, Bayer, Biolab, Hypera, Sanofi</td>
              <td align="center" valign="top">Bayer, Boehringher, MSD</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">Biolab, Daiichi Sankyo, Pfizer</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Roberto Gamarski</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Ronaldo Fernandes Rosa</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Silvio Carlos de Moraes Santos</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Siulmara Cristina Galera</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Stela Maris da Silva Grespan</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">Teresa Cristina Rogerio da Silva</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
            <tr>
              <td align="left" valign="top">William Antonio de Magalh&#227;es Esteves</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
              <td align="center" valign="top">No</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <sec>
        <title>1. General Aspects of Old Age, Risk Factors, and Prevention</title>
        <sec>
          <title>1.1. Demographic and Epidemiological Aspects</title>
          <p>Since the second half of the 20<italic>th</italic> Century, survival has been democratized in numerous countries around the world. This means that more people are reaching more advanced ages. In Brazil, in 1980, of every 100 female live births, 30 could be expected to reach their 80<italic>th</italic> birthday; in 2013, this number increased to 55. The average lifespan of the Brazilian population, consequently, increased nearly 12 years during this period. One of the factors responsible for this phenomenon was the decrease in advanced age mortality, which was the result of the control of theretofore lethal diseases. However, many of these diseases that ceased to be lethal are still not curable. As a consequence, the aged population, which continues aging and becomes more heterogeneous, has grown. This heterogeneity is due to differentiated gender, age, and epidemiological profile, among other factors. For example, of the approximately 26 million people age 60 or over, 56.4% were women, and 13.8% were age 80 or over. It is worth highlighting that not only is the aging process expected to increase, but the aged populated itself is also expected to age further. Or be it, the population age 80 or over is the one that grows the most, given the reduced mortality in this age group<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> (<xref ref-type="table" rid="t46">Table 1</xref>). It is known that advanced age leads to the need to live with chronic, incapacitating diseases, which may compromise individual autonomy. In 2013, only 22.3% of elderly Brazilians declared that they had no chronic diseases. Approximately half, 48.6%, declared that they had 1 or 2 diseases, and 29.1% declared 3 or more. Women have a higher likelihood of contracting a disease than men, 81.2%, compared to 73.1%. This higher proportion of women in the elderly age group means a higher proportion of people with chronic morbidity<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> (<xref ref-type="table" rid="t47">Table 2</xref>). Within diseases reported, cardiovascular diseases (CVD) are predominant. For example, 62.0% of men and 67.4% of women declare that they have hypertension, and 23.2% and 36.9% of men and women, respectively, declare high cholesterol. These diseases also constitute the main cause of death in the elderly population, accounting for 34.2% and 35.2% of deaths in men and women, respectively. Within CVD, acute myocardial infarction (AMI) and stroke stand out<xref ref-type="bibr" rid="B2"><sup>2</sup></xref> (Tables <xref ref-type="table" rid="t48">3</xref> and <xref ref-type="table" rid="t49">4</xref>).</p>
          <table-wrap id="t46">
            <label>Table 1</label>
            <caption>
              <title>Percentage distribution of the elderly population by sex and age<xref ref-type="bibr" rid="B1"><sup>1</sup></xref></title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup width="25%">
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="center" valign="top"/>
                  <th align="center" valign="top">Men</th>
                  <th align="center" valign="top">Women</th>
                  <th align="center" valign="top">Total</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">60 to 69</td>
                  <td align="center" valign="top">56.5</td>
                  <td align="center" valign="top">56.3</td>
                  <td align="center" valign="top">56.4</td>
                </tr>
                <tr>
                  <td align="left" valign="top">70 to 79</td>
                  <td align="center" valign="top">30.7</td>
                  <td align="center" valign="top">29.4</td>
                  <td align="center" valign="top">30</td>
                </tr>
                <tr>
                  <td align="left" valign="top">80 to 89</td>
                  <td align="center" valign="top">10.8</td>
                  <td align="center" valign="top">12.2</td>
                  <td align="center" valign="top">11.6</td>
                </tr>
                <tr>
                  <td align="left" valign="top">90 or over</td>
                  <td align="center" valign="top">2</td>
                  <td align="center" valign="top">2.1</td>
                  <td align="center" valign="top">2</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Total</td>
                  <td align="center" valign="top">100</td>
                  <td align="center" valign="top">100</td>
                  <td align="center" valign="top">100</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN12">
                <p>Brazil, 2013.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <table-wrap id="t47">
            <label>Table 2</label>
            <caption>
              <title>Proportion of elderly people with chronic diseases by number of pathological conditions<xref ref-type="bibr" rid="B1"><sup>1</sup></xref></title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup width="25%">
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="center" valign="top"/>
                  <th align="center" valign="top">Men</th>
                  <th align="center" valign="top">Women</th>
                  <th align="center" valign="top">Total</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">None</td>
                  <td align="center" valign="top">26.9</td>
                  <td align="center" valign="top">18.8</td>
                  <td align="center" valign="top">22.3</td>
                </tr>
                <tr>
                  <td align="left" valign="top">1 to 2</td>
                  <td align="center" valign="top">49.4</td>
                  <td align="center" valign="top">48</td>
                  <td align="center" valign="top">48.6</td>
                </tr>
                <tr>
                  <td align="left" valign="top">3 or more</td>
                  <td align="center" valign="top">23.7</td>
                  <td align="center" valign="top">33.3</td>
                  <td align="center" valign="top">29.1</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN13">
                <p>Brazil, 2013.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <table-wrap id="t48">
            <label>Table 3</label>
            <caption>
              <title>Main causes of death in the elderly population by age<xref ref-type="bibr" rid="B2"><sup>2</sup></xref></title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="center" valign="top"/>
                  <th align="center" valign="top">Men</th>
                  <th align="center" valign="top">Women</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Circulatory system diseases</td>
                  <td align="center" valign="top">34.2</td>
                  <td align="center" valign="top">35.2</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Neoplasm</td>
                  <td align="center" valign="top">19</td>
                  <td align="center" valign="top">15.5</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Respiratory system diseases</td>
                  <td align="center" valign="top">14.3</td>
                  <td align="center" valign="top">14.7</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Endocrine, nutritional, and metabolic diseases</td>
                  <td align="center" valign="top">6.5</td>
                  <td align="center" valign="top">8.9</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Poorly defined</td>
                  <td align="center" valign="top">6.2</td>
                  <td align="center" valign="top">6.2</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Others</td>
                  <td align="center" valign="top">19.9</td>
                  <td align="center" valign="top">19.5</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Total</td>
                  <td align="center" valign="top">100</td>
                  <td align="center" valign="top">100</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN14">
                <p>Brazil, 2013.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <table-wrap id="t49">
            <label>Table 4</label>
            <caption>
              <title>Main causes of death due to circulatory system disease by sex<xref ref-type="bibr" rid="B2"><sup>2</sup></xref></title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="center" valign="top"/>
                  <th align="center" valign="top">Men</th>
                  <th align="center" valign="top">Women</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Acute myocardial infarction</td>
                  <td align="center" valign="top">26</td>
                  <td align="center" valign="top">21.4</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Strokes not specified as hemorrhagic or ischemic</td>
                  <td align="center" valign="top">13.7</td>
                  <td align="center" valign="top">13.7</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Heart failure</td>
                  <td align="center" valign="top">8.2</td>
                  <td align="center" valign="top">9.4</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Others</td>
                  <td align="center" valign="top">52</td>
                  <td align="center" valign="top">55.5</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Total</td>
                  <td align="center" valign="top">100</td>
                  <td align="center" valign="top">100</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN15">
                <p>Brazil, 2013.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>This indicates a greater need for prevention, with lifestyle changes, alcohol and tobacco control, better diet, and physical exercise being able to contribute to a reduction in CVD. In summary, it is possible to affirm that humanity seems to be making the dream of long life come true, but it is necessary to avoid the Tithonus trap. Tithonus was a mythical Trojan hero who was granted eternal life; he forgot, however, to ask for eternal youth. Eventually he was transformed into a cricket. Ulysses, on the other hand, declined the gift of immortality, Ulysses, on the other hand, declined the gift of immortality, preferred remain owner of his destiny and his soul (Homero). Or be it, living a long life, with autonomy, should be humanity&#8217;s dream.</p>
        </sec>
        <sec>
          <title>1.2. Interpretation of Frailty</title>
          <p>Frailty is a biological syndrome characterized by decreased homeostatic reserve and resistance to various stressors. It results in cumulative decreases in multiple physiological systems and leads to increased vulnerability and unfavorable clinical outcomes, such as falls, impaired mobility and functional decline, hospitalization, institutionalization, and a higher risk of death.<xref ref-type="bibr" rid="B3"><sup>3</sup></xref> This state of vulnerability causes an apparently minor injury (e.g., infection, introduction of a new medication, or even a small surgery) to lead to an evident, disproportional change in the patient&#8217;s state of health; these changes may by exemplified as alterations from independent to dependent status, from able to move to immobile, from balance and stable gait speed to risk of falling, or from lucid to delirious.<xref ref-type="bibr" rid="B4"><sup>4</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B5"><sup>5</sup></xref></p>
          <p>There is an overlap, but not a concurrence in the incidence of frailty, incapacity, and multimorbidity (coexistence of two or more chronic diseases). Although they are less frequent, there are frail individuals who have neither incapacity nor multimorbidity.<xref ref-type="bibr" rid="B4"><sup>4</sup></xref> Sarcopenia (decreased muscle mass and function) is a component of the syndrome of frailty, which is more multifaceted and complex than sarcopenia alone.<xref ref-type="bibr" rid="B5"><sup>5</sup></xref></p>
          <p>Clinical presentation results not only from a single well defined disease, but rather from the accumulation of impairments in multiple organic systems, and it occurs when the accumulated effects of these impairments compromises the organism&#8217;s compensatory capacity. A systematic review demonstrated that the prevalence of frailty among community-dwelling elderly people was 10.7% (varying from 4.0% to 59.1%).<xref ref-type="bibr" rid="B6"><sup>6</sup></xref></p>
          <p>In CVD patients, frailty confers a 2-fold risk of death, and this effect continues after adjusting for comorbidities and age. Numerous studies have also demonstrated an increase in the prevalence of frailty among patients with CVD, such as coronary artery disease (CAD), heart failure (HF), heart valve disease, etc. A higher risk of complications and mortality has also been identified in frail elderly patients who undergo cardiovascular interventions such as surgery and angioplasty.<xref ref-type="bibr" rid="B7"><sup>7</sup></xref></p>
          <p>Frailty may potentially be prevented or treated, and many studies have demonstrated that exercise, protein/caloric supplementation, vitamin D supplementation, and reduction and optimization of polypharmacy may decrease levels of frailty, thus minimizing adverse outcomes and risks of interventions.<xref ref-type="bibr" rid="B5"><sup>5</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B8"><sup>8</sup></xref></p>
          <p>The identification of frail elderly patients is advocated so that multidimensional interventions may be implemented, mainly physical and nutritional rehabilitation, which reduces or postpones adverse outcomes and provides risk prognosis. It is necessary to emphasize that the identification of frailty does not need to be seen as a reason to exclude or suspend treatment, but rather as a means of programming individualized, patient-centered interventions.<xref ref-type="bibr" rid="B5"><sup>5</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B7"><sup>7</sup></xref></p>
          <p>Fried et al. (2001), in a longitudinal cardiovascular cohort study, identified the following manifestations for this syndrome: unintentional weight loss, muscular weakness, exhaustion (fatigue), decreased gait speed, and decreased degree of physical activity. Based on this, they proposed diagnostic criteria known as the &#8220;Fried et al. Frailty Phenotype&#8221;,<xref ref-type="bibr" rid="B3"><sup>3</sup></xref> or &#8220;Cardiovascular Health Study Frailty Screening Scale&#8221;.<xref ref-type="bibr" rid="B3"><sup>3</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B5"><sup>5</sup></xref> These criteria have been criticized, insofar as those referring to exhaustion and decreased physical activity are not objective and are difficult to evaluate in daily practice with elderly patients. Other indexes and scales for diagnosis have been proposed, such as Rockwood Clinical Frailty Scale,<xref ref-type="bibr" rid="B9"><sup>9</sup></xref> the G&#233;rontop&#244;le Frailty Screening Tool,<xref ref-type="bibr" rid="B10"><sup>10</sup></xref> the FRAIL scale proposed by Van Kan and Morley,<xref ref-type="bibr" rid="B11"><sup>11</sup></xref> the Groningen Frailty Indicator,<xref ref-type="bibr" rid="B12"><sup>12</sup></xref> the Tilburg Frailty Indicator,<xref ref-type="bibr" rid="B13"><sup>13</sup></xref> the PRISMA-7 questionnaire,<xref ref-type="bibr" rid="B14"><sup>14</sup></xref> the VES-13 Scale,<xref ref-type="bibr" rid="B15"><sup>15</sup></xref> and the Edmonton Frailty Scale.<xref ref-type="bibr" rid="B16"><sup>16</sup></xref> The latter five instruments have been transculturally adapted and/or validated in Brazil. Studies have demonstrated that the 5-meter gait speed test is a useful tool for evaluating frailty in elderly patients referred for percutaneous aortic valve implantation.<xref ref-type="bibr" rid="B17"><sup>17</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B18"><sup>18</sup></xref> The incorporation of this tool into the Society of Thoracic Surgeons (STS) score improved its ability to predict adverse events. For a given STS score, the risk of mortality or morbidity was 2&#8211;3 times greater in patients with slow gait speed.<xref ref-type="bibr" rid="B17"><sup>17</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B18"><sup>18</sup></xref> Regardless of the instrument used to screen and identify, the syndrome of frailty should be investigated in all individuals over age 70 and in elderly patients with CVD, even if they are below this age group, and prevention and treatment measures should be put into practice.<xref ref-type="bibr" rid="B5"><sup>5</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B7"><sup>7</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B8"><sup>8</sup></xref></p>
        </sec>
        <sec>
          <title>1.3. Particularities in the Evaluation of Elderly Patients</title>
          <p>Aging is a risk factor for most CVD, as well as numerous comorbidities, making the elderly the most heterogeneous and most complex adult age group.<xref ref-type="bibr" rid="B19"><sup>19</sup></xref> Generally speaking, the healthcare system is poorly prepared to attend patients with multimorbidities, given that they require greater individualization, as well as assistance from a multiprofessional team that works integratedly.<xref ref-type="bibr" rid="B20"><sup>20</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B21"><sup>21</sup></xref></p>
          <p>Interventions which are clearly beneficial in adults are, generally, also beneficial for elderly patients. However, the peculiarities which exist regarding evaluation of elderly patients are fundamental for their individual treatment. The evaluation of elderly patients should be performed using the Broad Geriatric Assessment (<italic>Avalia&#231;&#227;o Geri&#225;trica Ampla</italic>, AGA).<xref ref-type="bibr" rid="B22"><sup>22</sup></xref> This is a multidimensional, generally interdisciplinary, diagnostic process for determining impairments, inabilities, and disadvantages in elderly patients and, thus, planning their medium- to long-term care and assistance. The AGA prioritizes functional status and quality of life, facilitating communication between interdisciplinary team members. It should be applied to frail elderly patients and patients with multimorbidities. The AGA is also an important predictor of unfavorable outcomes, i.e., it has prognostic value for surgery, oncology, and orthopedic patients.<xref ref-type="bibr" rid="B22"><sup>22</sup></xref> The AGA is fundamental in the context of evaluating elderly patients. It includes, at least, 4 principal dimensions, which are functional capacity, medical conditions, social functionality, and mental health.<xref ref-type="bibr" rid="B22"><sup>22</sup></xref></p>
          <p>Independent elderly patients with a long life expectancy should be treated comprehensively in a manner that combines prevention and intervention. On the other hand, pre-frail and frail patients require more attention regarding their individual needs and priorities, as well as risk-benefit assessment for individualized therapeutic decisions.<xref ref-type="bibr" rid="B19"><sup>19</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B20"><sup>20</sup></xref> Goals to be reached should, equally, depend on functional status, without contraindicating any treatment whatsoever exclusively on account of age.</p>
          <p>Considering the high prevalence of multimorbidities and the high evolution of therapeutic options, polypharmacy has become very frequent in elderly patients, posing further challenges to case management.<xref ref-type="bibr" rid="B19"><sup>19</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B20"><sup>20</sup></xref> Understanding the advantages and disadvantages of every treatment is fundamental to adequate elderly treatment. This may only be scaled through the AGA. Familiarity with the AGA is, thus, essential to the evaluation and introduction of a determined treatment in an elderly patient.<xref ref-type="bibr" rid="B21"><sup>21</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B22"><sup>22</sup></xref></p>
        </sec>
        <sec>
          <title>1.4. Particularities in the Treatment of Elderly Patients</title>
          <p>In treating elderly patients, priority is given to the patient who is ill, rather than to the illness, and to controlling the disease, rather than curing it. It is essential to know the disease, the patient who has the disease, and the treatment. CVD is frequent, and, even when there are few manifestations, it brings increased risks; elderly patients with diseases present comorbidities and high biopsychosocial vulnerability; treatments are more susceptible to undesired effects. Thus, evaluation of multiple clinical and psychosocial domains is fundamental. Owing to the fact that evidence is often lacking, conduct should be individualized. Decisions should be shared, and it is necessary to consider risk-benefit ratio and life expectancy. In elderly patients, treatment indication requires more caution. Although therapeutic goals are less precise, excluding them solely on the basis of age implies omission.<xref ref-type="bibr" rid="B23"><sup>23</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B26"><sup>26</sup></xref></p>
          <p>Orientations regarding lifestyle changes are recommended, as in younger age groups. This may, however, cause undesired effects, especially if the changes are misunderstood or misapplied. Changing old habits requires attention.</p>
          <p>Pharmacological treatments should: prioritize conditions and restrict number of medications, simplify posology, evaluate and stimulate satisfactory adherence even in secondary prevention following AMI,<xref ref-type="bibr" rid="B26"><sup>26</sup></xref> provide orientation regarding problems related to self-medication, consider modifications in pharmacology related to age which, generally, recommend reducing doses, and evaluate possible drug interactions, given that &#8220;polypharmacy&#8221; is common. Beers Criteria, informally known as the &#8220;Beers List,&#8221; are a reference on safety in prescribing medications to the elderly. They were created in 1991, by the geriatrician Mark H. Beers, and they are periodically revised, the 2015 version being the most recent.<xref ref-type="bibr" rid="B27"><sup>27</sup></xref></p>
          <p>In the United States, more than one third of emergency room visits due to adverse effects of substances occur in individuals over age 65. They imply hospitalization of more than 40% of cases, and this frequency is increasing over time. Of these visits, nearly 60% were related to the use of anticoagulants, antidiabetic agents, and opioid analgesics, and nearly 2% were related to restricted use medications, in accordance with the Beers Criteria.<xref ref-type="bibr" rid="B28"><sup>28</sup></xref></p>
          <p>Recently, the Food and Drug Administration Adverse Event Reporting System (FAERS) drew attention to evaluating the eventual need for regulatory action for the following: the anticoagulants apixaban, edoxaban, rivaroxaban, and dabigatran, due to reports of vasculitis; ivabradine, due to potential signs of ventricular arrhythmias; and midodrine, due to reports of interactions with monoamine oxidase inhibitors (MAOI) which could trigger a stroke.<xref ref-type="bibr" rid="B29"><sup>29</sup></xref></p>
          <p>Interventional treatments should be carefully based on criteria, with the participation of heart teams, and performed by experienced and qualified teams, given that they present more frequent and severe complications.</p>
          <p>A noteworthy example of this scenario is the need for hospitalization and admission to skilled nursing facilities in 4 of every 5 elderly patients who received an implantable cardioverter-defibrillator for secondary prevention of sudden cardiac death, even though they survived at least 2 years.<xref ref-type="bibr" rid="B30"><sup>30</sup></xref></p>
        </sec>
        <sec>
          <title>1.5. Diabetes Mellitus in Elderly Patients</title>
          <p>The National Health Survey conducted by the Brazilian Institute of Geography and Statistics (IBGE, 2013) showed a 19.9% prevalence of diabetes mellitus in individuals in the 65&#8211;74 age group.<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> In diabetic adults, there is an increase in mortality and a decrease in functional capacity with consequent increase in the risk of institutionalization.<xref ref-type="bibr" rid="B31"><sup>31</sup></xref> The presence of multimorbidities and comorbidities associated with this group&#8217;s high heterogeneity means that the elderly are often excluded from randomized clinical trials, making disease management more difficult in this population.<xref ref-type="bibr" rid="B31"><sup>31</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B32"><sup>32</sup></xref></p>
          <p>Diagnostic criteria for diabetes mellitus in the elderly are similar to those in younger populations: (1) fasting blood glucose &#8805; 126 mg/dL; or (2) random blood glucose &#8805; 200 mg/dL, associated with disease symptoms; or (3) blood glucose 2 hours after a 75-g glucose load &#8805; 200 mg/dL; or (4) glycated hemoglobin (HbA1C) &#8805; 6.5% (provided that the laboratory is standardized). The American Diabetes Association (ADA) recommends that individuals who are overweight as a risk factor and all adults &#8805; age 45 be screened for diabetes every 1 to 3 years, with fasting blood glucose, glycated hemoglobin dosage, or oral glucose tolerance test, for the benefit of early diagnosis, early treatment, and prevention of complications.<xref ref-type="bibr" rid="B31"><sup>31</sup></xref></p>
          <p>Elderly individuals with diabetes are at a higher risk of developing geriatric syndromes, such as polypharmacy, cognitive impairment, urinary incontinence, falls, and chronic pain. When individuals with these syndromes develop diabetes, their clinical condition worsens. Thus, in addition to screening for complications, multidimensional evaluation of elderly diabetic individuals is also fundamental. It becomes imperative to perform AGA with mental, functional, nutritional, and social evaluations for these individuals in order to define goals to be met for each patient.<xref ref-type="bibr" rid="B32"><sup>32</sup></xref> The objective should be defined between two options: intensive blood glucose control, with less progression of chronic complications; or standard blood glucose control, in order to avoid only symptoms of hyperglycemia and acute complications.</p>
          <p>The United Kingdom Prospective Diabetes Study (UKPDS), although it excluded elderly patients, showed the benefits of intensive blood glucose control in individuals as they age, with posterior follow-up.<xref ref-type="bibr" rid="B33"><sup>33</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B34"><sup>34</sup></xref> There are 3 main randomized clinical trials with the participation of elderly patients and intensive blood glucose control. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study was interrupted due to mortality in the youngest group; however, hypoglycemia and other adverse effects of treatment were more common in elderly patients;<xref ref-type="bibr" rid="B35"><sup>35</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B36"><sup>36</sup></xref> in the Action in Diabetes and Vascular Disease: Preteraax and Diamicron MR Controlled Evaluation (ADVANCE) study, the risk of hypoglycemia and hospitalization increased significantly;<xref ref-type="bibr" rid="B37"><sup>37</sup></xref> and in the Veterans Affairs Diabetes Trial (VADT) study, there were no benefits, with the exception of decreased progression of microalbuminuria.<xref ref-type="bibr" rid="B38"><sup>38</sup></xref> Two retrospective studies (U.K. General Practice Research Database, 2009<xref ref-type="bibr" rid="B39"><sup>39</sup></xref> and The Diabetes and Aging Study, 2011) show a U-shaped curve relating mortality and blood glucose levels.<xref ref-type="bibr" rid="B40"><sup>40</sup></xref> Individualization of treatment is, thus, imperative in elderly patients in accordance with their clinical, functional, and life expectancy profile, as demonstrated in <xref ref-type="table" rid="t50">Table 5</xref>, with treatment goals for arterial hypertension and dyslipidemia in elderly patients with diabetes.</p>
          <table-wrap id="t50">
            <label>Table 5</label>
            <caption>
              <title>Treatment goals regarding blood glucose, and dyslipidemia in elderly patients with diabetes</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup width="14%">
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="middle">Patient characteristics/ health status</th>
                  <th align="center" valign="middle">Rationale</th>
                  <th align="center" valign="middle">Reasonable HbA1C goal</th>
                  <th align="center" valign="middle">Fasting or preprandial blood glucose (mg/dL)</th>
                  <th align="center" valign="middle">Bedtime blood glucose (mg/dL)</th>
                  <th align="center" valign="middle">Blood pressure (mmHg)</th>
                  <th align="center" valign="middle">Lipids</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="middle">Healthy (few coexisting chronic diseases, cognitive and functional state intact)</td>
                  <td align="center" valign="middle">Long life expectancy</td>
                  <td align="center" valign="middle">&lt; 7.5%</td>
                  <td align="center" valign="middle">90&#8211;130</td>
                  <td align="center" valign="middle">90&#8211;150</td>
                  <td align="center" valign="middle">&lt; 140/90</td>
                  <td align="center" valign="middle">Statin, provided there is no contraindication or intolerance</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">Complex/intermediate (multiple coexisting chronic diseases, impaired IADL, or mild to moderate cognitive impairment)</td>
                  <td align="center" valign="middle">Intermediate life expectancy, high treatment burden, vulnerability to hypoglycemia, fall risk</td>
                  <td align="center" valign="middle">&lt; 8.0%</td>
                  <td align="center" valign="middle">90&#8211;150</td>
                  <td align="center" valign="middle">100&#8211;180</td>
                  <td align="center" valign="middle">&lt; 140/90</td>
                  <td align="center" valign="middle">Statin, provided there is no contraindication or intolerance</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">Very complex/ poor health (long-term care or end-stage chronic disease, moderate to severe cognitive impairment, or 2+ BADL dependencies)</td>
                  <td align="center" valign="middle">Limited life expectancy makes benefit uncertain</td>
                  <td align="center" valign="middle">&lt; 8.5%</td>
                  <td align="center" valign="middle">100&#8211;180</td>
                  <td align="center" valign="middle">110&#8211;200</td>
                  <td align="center" valign="middle">&lt; 150/90</td>
                  <td align="center" valign="middle">Consider the probability of benefits of statin (secondary prevention, rather than primary)</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN16">
                <p>BADL: basic activities of daily living; HbA1C: glycosylated hemoglobin; IADL: instrumental activities of daily living. Source: American Diabetes Association. Older adults. Diabetes Care. 2017; 40 (suppl.1):S99-S104.<xref ref-type="bibr" rid="B32"><sup>32</sup></xref></p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>1.6. Tobacco Use</title>
          <p>The influence of tobacco use in elderly individuals occurs due to anatomical and physiological alterations in a cumulative process which leads to endothelial dysfunction, increased platelet adhesion, decreased high-density lipoprotein cholesterol (HDL-c), and increased low-density lipoprotein cholesterol (LDL-c), among other alterations.<xref ref-type="bibr" rid="B41"><sup>41</sup></xref> Tobacco use is common in the elderly population, and it is an important cause of morbidity and mortality, including CVD, peripheral vascular disease, cerebrovascular disease, cancer, and obstructive pulmonary disease. On the other hand, the tobacco cessation has benefits, even in elderly patients, with respect to the prevention of these diseases or, at least, to slowing the decline of pulmonary function.<xref ref-type="bibr" rid="B42"><sup>42</sup></xref> The Systolic Hypertension in the Elderly Program Study<xref ref-type="bibr" rid="B43"><sup>43</sup></xref> observed patients with an average age of 72 and showed a significant increase in AMI, sudden death, and stroke in smokers, compared with non-smokers. Exposure to long periods of passive tobacco use increases the risk of developing CAD. Kawachi et al. (1997)<xref ref-type="bibr" rid="B44"><sup>44</sup></xref> followed 32,000 non-smoking women, between the ages of 36 and 71, for 10 years, and found that the relative risk of developing coronary heart disease increased in women exposed to smoking. Occasional exposure to cigarettes increased their relative risk by 1.58, and regular exposure increased the relative risk by 1.91.<xref ref-type="bibr" rid="B45"><sup>45</sup></xref> Tobacco use constitutes a risk factor for dementia, and cessation may reduce the burden of dementia. Passive exposure to smoking may also increase the risk of dementia.<xref ref-type="bibr" rid="B46"><sup>46</sup></xref> Studies show that elderly smokers have a lower intention of quitting in comparison with younger smokers; they have, on the other hand, a higher likelihood of success when they do try to stop smoking.<xref ref-type="bibr" rid="B47"><sup>47</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B48"><sup>48</sup></xref> Success in stopping is frequently achieved after an acute coronary event, aggravation of chronic obstructive pulmonary disease (COPD), or symptomatic and limiting peripheral arterial disease. Medical advice to cease smoking should be firm, with emphasis placed on the short- and medium-term benefits. Aggressive practices related to tobacco cessation should be adopted.<xref ref-type="bibr" rid="B49"><sup>49</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B50"><sup>50</sup></xref> Evidence shows the efficiency of using the 4 As method in elderly patients, namely: ask, advise, assist, and arrange follow up.<xref ref-type="bibr" rid="B51"><sup>51</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B52"><sup>52</sup></xref> Different approaches, such as interventions through individual counseling performed by healthcare professionals, age-appropriate self-help material, use of nicotine (transdermal patches or chewing gum), or use of specific medications, e.g. bupropion), have also been shown to be efficient in treating tobacco use.<xref ref-type="bibr" rid="B53"><sup>53</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B55"><sup>55</sup></xref></p>
          <table-wrap id="t51">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="middle">Recommendations</th>
                  <th align="center" valign="middle">Grade of recommendation</th>
                  <th align="center" valign="middle">Level of evidence</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="middle">Tobacco use is a modifiable risk factor for CVD in elderly individuals and cessation is recommended</td>
                  <td align="center" valign="middle">I</td>
                  <td align="center" valign="middle">C</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">Use of multidisciplinary approaches, with the 4 As Method, is recommended: ask, advise, assist, and arrange follow up</td>
                  <td align="center" valign="middle">I</td>
                  <td align="center" valign="middle">C</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">Nicotine/bupropion transdermal patches or chewing gum may be used to cease tobacco use</td>
                  <td align="center" valign="middle">IIa</td>
                  <td align="center" valign="middle">C</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN25a">
                <p><italic>CVD: cardiovascular disease</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>1.7. Obesity</title>
          <p>The prevalence of overweight status and obesity has increased over the past decades in all age groups, including the elderly.<xref ref-type="bibr" rid="B56"><sup>56</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B57"><sup>57</sup></xref></p>
          <p>Both obesity and overweight status have been associated with the risk of all cause and CVD mortality, in the general population.<xref ref-type="bibr" rid="B58"><sup>58</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B60"><sup>60</sup></xref></p>
          <p>The majority of these studies mainly involved young adult patients, making this relationship less evident in the elderly.<xref ref-type="bibr" rid="B61"><sup>61</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B64"><sup>64</sup></xref></p>
          <p>Some meta-analysis studies have reported that overweight and obese elderly individuals, when compared with elderly individuals within the normal weight range, had lower mortality rates and lower or no risk of CVD. This effect has been called the &#8220;obesity paradox&#8221;.<xref ref-type="bibr" rid="B65"><sup>65</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B67"><sup>67</sup></xref></p>
          <p>In addition to possible confounding factors in these studies, other reasons may be involved. The index used to measure and classify body mass was the body mass index (BMI). Degrees of obesity adopted by the World Health Organization (WHO), with respect to BMI, are: overweight (25.0 to 29.9 kg/m<sup>2</sup>) and obese (over 30.0 kg/m<sup>2</sup>).<xref ref-type="bibr" rid="B68"><sup>68</sup></xref> Variables such as age, sex, and race may affect BMI. With aging, changes in body composition occur, such as increased visceral fat and decreased muscle mass. Loss of height may also occur, owing to compression of vertebral bodies or kyphosis. In this manner, BMI becomes less precise in measuring fat mass. When used alone, it is not able to be an accurate predictor of CVD risk in elderly patients. For instance, some elderly individuals may be considered overweight by body fat patterns without having a BMI over 25 kg/m<sup>2</sup>.</p>
          <p>Using BMI alone, we may be underestimating the degree of adiposity in individuals who lost muscle mass. Central obesity and nutrition are factors which seem more important in relation to mortality and CVD risk in this population. Some authors suggest that waist circumference (WC) could be a particularly important measure for elderly patients, which would be better than BMI at evaluating risk, given its association with visceral adiposity.<xref ref-type="bibr" rid="B69"><sup>69</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B70"><sup>70</sup></xref></p>
          <p>Another study indicates that the presence or absence of metabolic syndrome is more important than BMI in obese elderly patients, thus dividing this population into &#8220;healthy obese&#8221; (without metabolic syndrome) and obese with metabolic syndrome. The latter group has been strongly associated with increased risk of CVD regardless of BMI.<xref ref-type="bibr" rid="B71"><sup>71</sup></xref></p>
          <p>More studies are necessary to clarify the interrelation between aging, obesity, and cardiovascular risk and what the best measures parameter(s) would be. Weight management in the elderly and efforts to promote healthy aging should be based on an individual approach, taking into consideration the maintenance of muscle mass and strength, comorbidities, functional and social status, physical activity, and quality of life. Intentional weight loss in obese elderly patients improves their cardiovascular risk profile, reduces chronic inflammation, and is correlated with improved quality of life. Unintentional weight loss requires careful clinical assessment of the underlying cause. Furthermore, the identification of elderly patients with sarcopenic obesity is relevant to prognosis. Sarcopenia and sarcopenic obesity have been associated with a higher risk of CVD, especially in elderly men with this type of obesity.</p>
        </sec>
        <sec>
          <title>1.8. Sedentarism</title>
          <p>Regular physical activity is essential to healthy aging. Considering that aging in inevitable, the rhythm and magnitude of decline in physiological function may be influenced by an intervention comprising exercise/physical activity (<xref ref-type="table" rid="t52">Table 6</xref>).<xref ref-type="bibr" rid="B72"><sup>72</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B73"><sup>73</sup></xref></p>
          <table-wrap id="t52">
            <label>Table 6</label>
            <caption>
              <title>Centers for Disease Control and Prevention exercise guidelines for adults over age 65</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup width="50%">
                <col/>
                <col/>
              </colgroup>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Substantial health benefits</td>
                  <td align="center" valign="top">2 hours and 30 minutes (150 minutes) of moderate-intensity aerobic activity per week Muscle strengthening activities 2 or more days per week 1 hour and 15 minutes (75 minutes) of vigorous-intensity aerobic activity</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Additional health benefits</td>
                  <td align="center" valign="top">5 hours (300 minutes) of moderate-intensity aerobic activity per week Muscle strengthening activities 2 or more days per week 2 hours and 30 minutes (150 minutes) of vigorous-intensity aerobic activity</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN17">
                <p>Adapted from: Centers for Disease Control and Prevention (CDC). Physical activities for older adults. Available at: <ext-link ext-link-type="uri" xlink:href="https://www.cdc.gov/features/activity-older-adults/index.html">www.cdc.gov/features/activity-older-adults/index.html</ext-link>. Accessed: 18/02/2016.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>Aging is associated with skeletal muscle mass loss; reduced muscle strength, flexibility, cardiac output, and pulmonary function; changes in hormonal and immune system regulation; reduced bone density, and higher prevalence and incidence of sedentarism.<xref ref-type="bibr" rid="B74"><sup>74</sup></xref></p>
          <p>In sedentary elderly patients, walking may be a practical solution, evaluating heart rate (HR) before and after exercise. It is necessary to recognize that elderly people do not represent a uniform group of patients and chronological age in itself does not identify this special group.<xref ref-type="bibr" rid="B75"><sup>75</sup></xref></p>
          <p>Sedentarism is an important risk factor for CAD in elderly individuals. Some studies demonstrate that the relative risk of CAD attributable to sedentarism is comparable to that of hypertension, hyperlipidemia, and tobacco use. Sedentarism, as an important risk factor, is, in most cases, directly or indirectly associated with the causes or aggravation of various diseases, such as obesity, diabetes, arterial hypertension, anxiety, depression, dyslipidemia, atherosclerosis, respiratory disease, osteoporosis, and cancer.<xref ref-type="bibr" rid="B76"><sup>76</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B77"><sup>77</sup></xref> Systematic physical exercise helps control systemic arterial hypertension (SAH), by reducing peripheral arterial resistance, increasing HDL-c, reducing obesity and triglycerides, improving blood glucose control, preventing coronary disease, and decreasing mortality.<xref ref-type="bibr" rid="B77"><sup>77</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B78"><sup>78</sup></xref></p>
          <p>Furthermore, it improves sleep quality, cognitive function, and short-term memory; decreases degree of depression; reduces or slows the onset of dementia; reduces the risk of colon, breast, prostate, and rectal cancer; increases bone density; and decreases the incidence of femur and vertebrae fractures.<xref ref-type="bibr" rid="B77"><sup>77</sup></xref></p>
          <p>In elderly patients, pre-exercise clinical evaluation is very important. The goal of exercise and cardiovascular rehabilitation in elderly patients is to improve their functional capacity as much as possible. These objectives are reached through programs that aim to increase aerobic capacity, muscle strength, and flexibility.<xref ref-type="bibr" rid="B72"><sup>72</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B79"><sup>79</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B82"><sup>82</sup></xref></p>
          <p>The amount of physical activity should be individualized, considering each patient&#8217;s comorbidities and peculiarities.<xref ref-type="bibr" rid="B73"><sup>73</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B74"><sup>74</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B79"><sup>79</sup></xref></p>
          <p>Elderly individuals should spend more time warming up before and cooling down after activity. The warm-up phase includes flexibility and movement exercises, which facilitate musculoskeletal biomechanics. The post-exercise cool-down phase allows for the gradual dissipation of body heat and consequent peripheral vasodilatation. Musculoskeletal injuries may be decreased by avoiding high impact activities, such as running and jumping. Extreme care is necessary for activities using free weights, given the risk of accidents, especially in less skilled or more frail elderly patients.<xref ref-type="bibr" rid="B72"><sup>72</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B80"><sup>80</sup></xref> Walking briskly is an excellent way to obtain physical conditioning, with gradual increases in pace and distance covered.<xref ref-type="bibr" rid="B81"><sup>81</sup></xref> Elderly patients should be instructed to reduce exercise intensity on humid or hot days, given that skin blood flow decreases with age, consequently lowering the efficiency of sweating and thermal regulation.<xref ref-type="bibr" rid="B77"><sup>77</sup></xref> Practicing resistance exercise twice weekly is also recommended.</p>
          <p>Pre-participation assessment should begin with patient history and clinical exam, focusing on the particularities of this population, which often has silent atherosclerotic disease. Complementary investigation should be oriented by clinical data, avoiding high costs, which are sometimes prohibitive and may discourage physical exercise. Resting electrocardiogram (EKG) for the elderly has limited application as a pre-selection exam for physical activity.</p>
          <p>If possible, an exercise test (ET) should be performed in all elderly patients before initiating physical activity. The prevalence of coronary disease increases with age; the rationale behind the ET in this population may, thus, be even greater than in the general adult population.<xref ref-type="bibr" rid="B72"><sup>72</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B79"><sup>79</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B80"><sup>80</sup></xref> The ET is a procedure during which the patient undergoes programmed and individualized exercise, with the aim of evaluating clinical, metabolic, hemodynamic, autonomic, electrocardiographic, and, eventually, ventilatory responses to exercise. In elderly patients, modified protocols are used to perform the ET.<xref ref-type="bibr" rid="B79"><sup>79</sup></xref> If there are contraindications to performing the ET, stress EKG or scintigraphy should be performed. A Holter monitor is used to stratify risk in elderly patients with arrhythmias detected during EKG or ET, as well as those with a history of syncope.<xref ref-type="bibr" rid="B72"><sup>72</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B82"><sup>82</sup></xref></p>
          <p>Adherence to physical activity in this group has been increasingly positive. It is always necessary to consider that an active or latent pathological process may by present in an elderly individual and that the ET may contribute to defining it.<xref ref-type="bibr" rid="B83"><sup>83</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B84"><sup>84</sup></xref></p>
          <table-wrap id="t53">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="middle">Recommendations</th>
                  <th align="center" valign="top">Grade of recommendation</th>
                  <th align="center" valign="top">Level of evidence</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Clinical exam and electrocardiogram</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Electrocardiogram, exercise test, or myocardial scintigraphy in medium-risk patients or in moderate to intense exercise</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Physical exercise</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Resistance exercise</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
        </sec>
        <sec>
          <title>1.9. Dyslipidemia in Elderly Patients</title>
          <p>Dyslipidemia is a frequent diagnosis in elderly patients, mainly in women, owing to the fact that LDL-c levels tend to rise as they advance in age, especially after menopause; in men, however, LDL-c tends to decrease after age 55. Unlike in young adults, cases of de novo dyslipidemia are rare, and cases of dyslipidemia secondary to hypothyroidism (especially in women), diabetes mellitus, glucose intolerance, nephrotic syndrome, obesity, alcoholism, or use of medications such as thiazide diuretics and non-selective beta-adrenergic receptor blockers, are more common.<xref ref-type="bibr" rid="B85"><sup>85</sup></xref></p>
          <p>In relation to treatment, as elderly patients are often already at high risks (owing to the factor of age), the approach to dyslipidemia, regarding therapeutic decisions, should give greater consideration to the patient&#8217;s good general and mental state, his or her socio-economic conditions, family support, comorbidities present, and the use of other drugs that may influence adherence to and maintenance of therapy. Non-pharmacological orientations should follow the same principals of indication for young adults, more carefully observing caloric, protein, and vitamin intake needs and physical conditions for practicing exercise (recommendation I, evidence B). It is necessary to reiterate the importance of ceasing habits of smoking and excessive consumption of alcoholic beverages. After 90 days, if there is no response, drug treatment may be initiated, with the following precautions: (1) always start with low doses and, if necessary, increase, progressively; (2) analyze the cost-benefit ratio; and (3) verify the existence of socioeconomic conditions for maintaining long-term treatment and performing periodical clinical and laboratory exams, due to the higher likelihood of collateral effects and drug interactions.<xref ref-type="bibr" rid="B85"><sup>85</sup></xref></p>
          <p>For hypercholesterolemia, statins are the first choice.<xref ref-type="bibr" rid="B86"><sup>86</sup></xref> Tolerance is good; there is not a high incidence of undesired effects, even though muscle pain, cramps, and weakness, which are sometimes confounded with osteomuscular disease, may occur, even in low doses. Evidence from subgroup analyses in primary and secondary prevention studies and the Pravastatin in Elderly Individuals at Risk of Vascular Disease (PROSPER) study,<xref ref-type="bibr" rid="B87"><sup>87</sup></xref> specially designed for elderly patients with or without previous manifestations of atherosclerosis, demonstrated the following benefits to treatment for this age group: reduction of coronary events (grade of recommendation IIa, level of evidence B), stroke (grade of recommendation IIa, level of evidence B), and preservation of cognitive functions (grade of recommendation IIb, level of evidence B). When maximum statin dosages are not sufficient to meet recommended LDL-c goals, ezetimibe may be associated with the statins (grade of recommendation IIb, level of evidence B).<xref ref-type="bibr" rid="B88"><sup>88</sup></xref></p>
          <p>In cases of hypertriglyceridemia, fibrates are used (provided there are no gallstones or renal insufficiency). Fibrates and statins may be associated in cases of mixed dyslipidemia (elevated LDL-c and triglycerides), mainly with reduced HDL-c (grade of recommendation IIb, level of evidence D).<xref ref-type="bibr" rid="B88"><sup>88</sup></xref></p>
          <p>In secondary dyslipidemias, the fundamental concern is treating the triggering disease and substituting or removing inductor drugs. We should remember that elderly individuals, generally, use other drugs metabolized by cytochrome P450 (CYP450), which have the possibility of interacting with lipid-lowering agents, thus altering their blood concentration (grade of recommendation IIb, level of evidence D).<xref ref-type="bibr" rid="B88"><sup>88</sup></xref></p>
        </sec>
        <sec>
          <title>1.10. Depression and Cardiovascular Disease</title>
          <p>Depression and anxiety are highly prevalent in individuals with CAD and other CVD. They have been also been considered independent risk factors for CAD and CVD, in addition to altering their natural history.<xref ref-type="bibr" rid="B89"><sup>89</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B90"><sup>90</sup></xref></p>
          <p>Depression is disproportionally more frequent among CAD patients, with prevalence between 20% and 40%. It has also been reported that depression is prospectively associated with an increased risk of developing CAD,<xref ref-type="bibr" rid="B91"><sup>91</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B92"><sup>92</sup></xref> including AMI,<xref ref-type="bibr" rid="B93"><sup>93</sup></xref> at some point during life, as well as an increased risk of mortality.<xref ref-type="bibr" rid="B94"><sup>94</sup></xref> A 60-month follow-up study of 158 patients who suffered AMI revealed that greater depression was a significant predictor of mortality and adverse cardiac events.<xref ref-type="bibr" rid="B95"><sup>95</sup></xref></p>
          <p>Collateral effects of antidepressants on the cardiovascular system have been reported. These include bradycardia, tachycardia, hypertension, hypotension, orthostatic hypotension (OH), EKG alterations, altered electrolytes, reduced cardiac conduction, arrhythmias, and sudden cardiac death.<xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
          <sec>
            <title>1.10.1. Treating Depression and Anxiety in Patients with Cardiovascular Disease</title>
            <p>First generation antidepressants include MAOI and tricyclic and tetracyclic antidepressants (TCA and TeCA, respectively); second-generation antidepressants include selective serotonin reuptake inhibitors (SSRI), selective norepinephrine reuptake inhibitors (SNRI), and atypical antidepressants.<xref ref-type="bibr" rid="B89"><sup>89</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
            <p>Even though MAOI (phenelzine, tranylcypromine, moclobemide, selegiline, etc.) are effective, they present several unfavorable collateral effects, mainly OH, tachycardia, and hypertensive crises; the latter are also associated with stroke and acute aortic dissection and should, thus, be avoided in patients with CAD.<xref ref-type="bibr" rid="B89"><sup>89</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
            <p>The cardiovascular collateral effects of TCA (imipramine, amitriptyline, nortriptyline, desipramine, clomipramine, doxepin, maprotiline, etc.) are fairly well known, namely, increased HR, OH, slowed cardiac conduction, and increased QT interval variability.<xref ref-type="bibr" rid="B89"><sup>89</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B97"><sup>97</sup></xref> These effects, which have been reported not only in patients with CVD but also in people without previous cardiac disease, in addition to their anticholinergic action, make this class of drugs inappropriate for treating depression in elderly patients.<xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
            <p>SSRI (fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine, etc.) are considered the medications of choice for treating depression and anxiety in most cases, due to their acceptable safety profile and higher margins of non-toxic levels in comparison with other classes of antidepressants.<xref ref-type="bibr" rid="B89"><sup>89</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
            <p>Regarding efficacy of SSRI in decreasing symptoms of depression, all meta-analyses of selected indicators have shown that these antidepressants are more effective than placebo.<xref ref-type="bibr" rid="B98"><sup>98</sup></xref></p>
            <p>SSRI may cause prolonged QT intervals (reported mainly with fluoxetine and citalopram), but they do not generally lead to life-threatening arrhythmias in therapeutic doses. Citalopram appears to be the most cardiotoxic SSRI (conduction disturbances and arrhythmias).<xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
            <p>Most causes of prolonged QT interval and subsequent torsade de pointes (TdP) induced by SSRI are observed in patients with underlying vulnerabilities, such as congenital long QT syndrome, recent AMI, hypokalemia, or hypomagnesemia, or in cases of substance overdoses.<xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
            <p>Within this class, there is some evidence that escitalopram and sertraline have the best balance between effectiveness and acceptability for pharmacological treatment of depression in cardiac patients.<xref ref-type="bibr" rid="B99"><sup>99</sup></xref></p>
            <p>In summary, SSRI probably do not cause adverse effects when used according to the recommended dosages, and it has been suggested that, through complex mechanisms, they may bring some benefits to the cardiovascular system, such as lower rates of AMI in comparison with other types of antidepressants, especially TCA.<xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
            <p>As there are still no robust clinical orientations, patient treatments should be individualized in relation to potential risks and benefits. Additional studies are necessary to verify the exact cardiovascular safety profile.<xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
            <p>Regarding selective serotonin and norepinephrine reuptake inhibitors (SSNRI) (venlafaxine, desvenlafaxine, reboxetine, duloxetine, etc.), venlafaxine is associated with severe cardiotoxicity, only when given in high doses. Left ventricular (LV) failure, even in patients with no prior history of CVD, has also been reported in the literature.<xref ref-type="bibr" rid="B89"><sup>89</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B96"><sup>96</sup></xref> It is recommended to monitor blood pressure (BP) in patients who take SSNRI (especially venlafaxine), given that it has been reported to increase in epidemiological studies.<xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
            <p>Regarding atypical antidepressants (mirtazapine, agomelatine, nefazodone, trazodone, etc.), mirtazapine, in high doses, may cause hypotension and affect HR. Trazodone has minimal cholinergic activity; it may cause OH, and, in excess, prolonged QT and slowed atrioventricular conduction.<xref ref-type="bibr" rid="B96"><sup>96</sup></xref></p>
            <p>In addition to pharmacological treatment, psychotherapy and the prescription of non-medical treatments, such as physical activity, especially aerobic exercise and cardiac rehabilitation, are also indicated. These improve prognosis and patient quality of life and reduce risks of evolution of CAD and CVD.<xref ref-type="bibr" rid="B89"><sup>89</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B99"><sup>99</sup></xref></p>
          </sec>
        </sec>
        <sec>
          <title>1.11. Other Cardiovascular Risk Factors</title>
          <p>Traditional risk factors explain only half of CVD cases, which present high morbimortality rates. Several studies have been developed to look for possible new risk factors, known as emerging risk factors, as well as means of early diagnosis of CVD by investigating signs of subclinical atherosclerosis. The emerging risk factors covered in these Guidelines are hyperuricemia, C-reactive protein (CRP), vitamin D, genetic factors, coronary calcium score (CCS), and investigation of subclinical atherosclerosis.</p>
          <sec>
            <title>1.11.1. Hyperuricemia</title>
            <p>Recent epidemiological studies have demonstrated that hyperuricemia is frequently observed in patients with CVD or high risks thereof, such as arterial hypertension, CAD, peripheral vascular disease, HF, and stroke.<xref ref-type="bibr" rid="B100"><sup>100</sup></xref></p>
            <p>A recent meta-analysis of observational prospective studies on hyperuricemia and risk of stroke demonstrated a significant increase in the risk of stroke incidence and mortality, based on studies that adjusted traditional stroke risk factors, such as age, sex, hypertension, hypercholesterolemia, and blood glucose. Several pathophysiological mechanisms have been postulated, including endothelial dysfunction, oxidative metabolism, and platelet adhesiveness and aggregation. The role of hyperuricemia as an independent risk factor for CAD, however, remains controversial.<xref ref-type="bibr" rid="B101"><sup>101</sup></xref></p>
          </sec>
          <sec>
            <title>1.11.2. C-Reactive Protein</title>
            <p>The role of inflammation in the propagation of atherosclerosis and susceptibility to adverse cardiovascular events is well established. Even though CRP is involved in the immunological process which triggers vascular remodeling and platelet deposition and is associated with increased CVD risk, there is no definitive evidence for its role as a causal factor of atherothrombosis. The Jupiter study analyzed 9,261 elderly patients of both sexes, using ultrasensitive CRP (US-CRP) levels to determine whether or not they would receive rosuvastatin; the results were similar to those found in younger individuals, namely, a reduced occurrence of cardiovascular events.<xref ref-type="bibr" rid="B102"><sup>102</sup></xref></p>
            <p>Notwithstanding the publication of guidelines on the use of US-CRP for predicting CVD risk by several professional organizations, there is still a lack of consensus regarding optimal clinical use of US-CRP.<xref ref-type="bibr" rid="B103"><sup>103</sup></xref></p>
          </sec>
          <sec>
            <title>1.11.3. Vitamin D</title>
            <p>Recent studies show evidence of a strong association between vitamin D deficiency and the presence of SAH, metabolic syndrome, diabetes, and atherosclerosis. It is thus considered an emerging risk factor for CVD.<xref ref-type="bibr" rid="B104"><sup>104</sup></xref></p>
            <p>The mechanisms by which vitamin D exercises its role as a cardiovascular protector are still not well established. In the Third National Health and Nutrition Examination Survey (NHANES III), which involved 3,408 elderly patients, followed up for 7 years, after adjusting for cardiovascular risk, season of the year, and demographic data, verified that vitamin D levels are negatively associated with mortality risk, with this association being even stronger for cardiovascular mortality.<xref ref-type="bibr" rid="B105"><sup>105</sup></xref></p>
            <p>A meta-analysis of 19 prospective studies with more than 65,000 patients demonstrated that the risk of all CVD, as well as cardiovascular death and CAD, was lower in patients with higher levels of vitamin D.<xref ref-type="bibr" rid="B106"><sup>106</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B107"><sup>107</sup></xref></p>
          </sec>
          <sec>
            <title>1.11.4. Genetic Factors</title>
            <p>Aging is characterized by the complex interaction of cellular and molecular mechanisms that lead to a series of functional problems. These problems are intimately associated with one another; they include poor vasodilatation, increased arterial stiffness, and evident extracellular matrix remodeling, diffuse carotid intimal thickening, and endothelial dysfunction.</p>
            <p>The mechanisms by which age truly contributes to cardiovascular risk continue to be the object of speculation. Although this paradigm explains vascular aging, considering classic risk factors as causal mechanisms, a recently proposed alternative view on vascular aging has emerged, which presents new mechanistic alternatives for understanding the vascular aging process. In this new paradigm, causal mechanisms of the aging process in itself, most notably genomic instability, including telomeric wear, drive the harmful changes that increasingly occur with biological aging.<xref ref-type="bibr" rid="B108"><sup>108</sup></xref></p>
          </sec>
          <sec>
            <title>1.11.5. Coronary Calcium Score</title>
            <p>CCS represents an important risk marker for cardiovascular events, especially in predicting risk of AMI in subsequent years, with a score of 0 demonstrating an almost null possibility of coronary events in subsequent years. A score above 100, however, is considered an aggravating risk factor, and scores over 400 indicate a high risk of coronary events.<xref ref-type="bibr" rid="B109"><sup>109</sup></xref></p>
            <table-wrap id="t54">
              <table frame="hsides" rules="groups">
                <colgroup width="33%">
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <th align="left" valign="middle">Recommendations</th>
                    <th align="center" valign="top">Grade of recommendation</th>
                    <th align="center" valign="top">Level of evidence</th>
                  </tr>
                </thead>
                <tbody style="border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <td align="left" valign="top">Coronary calcium score</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                </tbody>
              </table>
            </table-wrap>
          </sec>
          <sec>
            <title>1.11.6. Investigating Subclinical Atherosclerosis</title>
            <p>This is indicated to better stratify cardiovascular risk in elderly patients, with the aim of better identifying cases that will require more aggressive therapy. The Cardiovascular Health Study followed up elderly patients for 10 years and demonstrated that the subclinical atherosclerosis index was a better predictor of cardiovascular events than traditional risk factors in asymptomatic elderly adults. This index is composed of the ankle-brachial index (ABI), carotid artery stenosis, carotid intima-media complex thickness, altered EKG or echocardiogram, positive response to the Rose questionnaire or the intermittent claudication questionnaire.<xref ref-type="bibr" rid="B110"><sup>110</sup></xref> Carotid artery ultrasonography is an important resource for evaluating elderly patients. Patients with carotid blockage of 50% or more are considered at a high risk of coronary events.<xref ref-type="bibr" rid="B111"><sup>111</sup></xref></p>
            <table-wrap id="t55">
              <table frame="hsides" rules="groups">
                <colgroup width="33%">
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <th align="left" valign="middle">Recommendations</th>
                    <th align="center" valign="top">Grade of recommendation</th>
                    <th align="center" valign="top">Level of evidence</th>
                  </tr>
                </thead>
                <tbody style="border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <td align="left" valign="top">Investigating subclinical atherosclerosis</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                </tbody>
              </table>
            </table-wrap>
            <sec>
              <label>1.11.6.1</label>
              <title>Ankle-brachial index</title>
              <p>Peripheral arterial obstructive disease (PAOD) is strongly related to coronary events, and it may be assessed by the ABI, a low-cost, easily applicable exam. ABI &lt; 0.9 is positively associated with a higher number of coronary events and with death of cardiovascular etiology. Its indication is always applicable when there are alterations in the clinical exam which suggest peripheral arterial disease, as well as excluding intermittent claudication (grade of recommendation IIa, level of evidence C). The recommendations of a recent American scientific statement highlight the strong, consistent association of advanced age with PAOD prevalence and incidence. Age &gt; 70 is an independent risk factor for developing PAOD involving lower extremities, notwithstanding other risk factors, with a prevalence rate of &gt; 20% in men and women in this age group. Given the strong effect of age on the prevalence of PAOD, the statement endorses the use of ABI as a class I recommendation (level of evidence C).<xref ref-type="bibr" rid="B112"><sup>112</sup></xref></p>
            </sec>
          </sec>
        </sec>
        <sec>
          <title>1.12. Aorta and Carotid Artery Disease</title>
          <sec>
            <title>1.12.1. Thoracic Aortic Aneurysm</title>
            <p>Bicuspid aortic valve (BAV) is the most frequent modality of congenital heart disease (1% to 2%), and it may occur with thoracic aortic aneurysm (TAA), with a high risk of undergoing expansion. As many as 50% of patients with BAV develop ascending aorta dilation. Factors that contribute to progression of TAA in the presence of SAH include obesity and increase in age. As these 3 conditions are frequently present together in elderly adults, TAA has been underdiagnosed in this age group. It is estimated that TAA is present in at least 3% to 4% of elderly individuals.</p>
            <p>Patients with TAA are in primary prevention. One of the complications of TAA is acute dissection, whose frequency is 2 times higher in men than in women. Rupture, however, is responsible for 60% of deaths attributed to TAA.</p>
            <p>Current guidelines consider a cutoff point for surgery indication for ascending TAA of 5.5 cm for patients without Marfan or BAV and 5.0 cm in the presence of one of these clinical conditions (<xref ref-type="table" rid="t56">Table 7</xref>). TAA with diameters &#8805; 4 cm require annual measurement, preferably by angiotomography (gold standard, but subject to radiation) or magnetic angioresonance. In non-genetic cases of TAA of &#8805; 5 cm, measurements should be performed biannually. EKG tends to underestimate aorta caliber.<xref ref-type="bibr" rid="B113"><sup>113</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B116"><sup>116</sup></xref></p>
            <table-wrap id="t56">
              <label>Table 7</label>
              <caption>
                <title>Threshold diameters for indicating aortic aneurysm surgery, according to current guidelines</title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup width="33%">
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <th align="left" valign="top">Aorta</th>
                    <th align="center" valign="top">Marfan/BAV</th>
                    <th align="center" valign="top">Non-marfan</th>
                  </tr>
                </thead>
                <tbody style="border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <td align="left" valign="top">Ascending</td>
                    <td align="center" valign="top">5.0 cm</td>
                    <td align="center" valign="top">5.5 cm</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Descending</td>
                    <td align="center" valign="top">6.0 cm</td>
                    <td align="center" valign="top">6.5 cm</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN18">
                  <p>BAV: bicuspid aortic valve.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
            <p>Elective TAA surgery mortality in highly specialized centers is 2.9%. The risk of stroke or paraplegia is much higher in descending aorta. In this case, the option of endovascular intervention, with stent collocation, presents lower risk of paraplegia.</p>
          </sec>
          <sec>
            <title>1.12.2. Abdominal Aortic Aneurysm</title>
            <p>Abdominal aortic aneurysms (AAA) tend to affect elderly individuals (&#8805; age 65) and are atherosclerotic in nature; in this manner, AAA places patients in secondary prevention. Tobacco use is the main etiological factor of AAA, which is 3 to 5 times more common in smokers than in non-smokers. AAA is also common in patients with peripheral arterial disease (PAD).<xref ref-type="bibr" rid="B115"><sup>115</sup></xref></p>
            <p>AAA is found in 1.3% of men between the ages of 45 and 54, and in 12.5% of those between the ages of 75 and 84. In women, the maximum prevalence was 5.2% in the elderly age group, being found in 0% of young women. The fact that men smoke more than women likely contributes to this pronounced difference between age groups by sex. This notwithstanding, evolution and prognosis of AAA are worse in women.<xref ref-type="bibr" rid="B113"><sup>113</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B115"><sup>115</sup></xref></p>
            <p>Initial discriminatory evaluation by ultrasonography is recommended, especially in male patients who have been smokers, starting at age 65. In the event that the result is normal, there is no need for periodic reevaluation.<xref ref-type="bibr" rid="B113"><sup>113</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B115"><sup>115</sup></xref></p>
            <p>AAA with diameters of &#8805; 4 cm require annual measurement, which may only be performed by abdominal ultrasonography, which, in this area, has excellent sensitivity and specificity. If it is &#8805; 5 cm, screening should be performed biannually. The cutoff point for indicating intervention is 5.5 cm. Open surgery poses a higher risk, but it lasts longer and should preferably be indicated in younger individuals with longer life expectancy. Endovascular intervention has evolved considerably and should preferably be indicated in older patients or patients considered high risk for surgery.<xref ref-type="bibr" rid="B113"><sup>113</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B116"><sup>116</sup></xref></p>
            <sec>
              <title>1.12.2.1. Carotid Arteries</title>
              <p>There is no solid evidence regarding the eventual advantage of interventional treatment in intensive clinical control of cardiovascular risk factors, especially if we consider the use of full dosages of latest generation of statins, although many services opt for aggressive treatment, based only on registers and specialist opinion.<xref ref-type="bibr" rid="B117"><sup>117</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B118"><sup>118</sup></xref></p>
              <p>Routine carotid ultrasonography is only indicated for patients who have suffered stroke/transient ischemic attack (TIA), or when physical examination identifies decreased, absent, or asymmetric pulse or carotid murmur.</p>
            </sec>
          </sec>
          <sec>
            <title>1.12.3. The Original and 10-Year CREST Studies</title>
            <p>The original Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) study (n = 2,502) aimed to observe the medium- and long-term reduction in risk of ischemic stroke associated with carotid endarterectomy (CEA) and angioplasty with carotid-artery stenting (CAS) in patients with significant carotid atherosclerotic disease. The proportion of cerebrovascular asymptomatic patients and of those who had suffered stroke/TIA was very similar. The main study objective was to evaluate the risk of death, AMI, or stroke during the first 30 days after the procedure and of ipsilateral stroke during the following 4 years. They did not, however, find an optimized clinical treatment group. The risk of minor stroke was higher in the CAS group during the first 30 days, whereas the risk of AMI was higher in the CEA group. At the end of the 4-year period, the risk of stroke was low and similar in both groups analyzed (2.0% and 2.4%; p = 0.85). The main conclusion was that both CEA and CAS may be alternatively indicated as interventional carotid treatments. Additional findings suggest that CEA seems to be more beneficial in elderly patients, while CAS would be more useful in subpopulations under age 65.<xref ref-type="bibr" rid="B117"><sup>117</sup></xref></p>
            <p>The main lesson of the 10-year CREST study was that, once the initial critical phase was over, patients who underwent interventional treatment tended to evolve very well long-term. The 10-year risk of stroke was 6.9% in the CAS group and 5.6% in the CEA group, with no significant statistical difference (p = 0.96). The primary composite endpoint (death, AMI, and stroke) occurred in 11.8% of participants in the CAS group and in 9.9% of those in the CEA group, with no statistical difference (p = 0.51). Nevertheless, the primary composite endpoint death/stroke over 10 years was worse in the CAS group (11.0% vs. 7.9%; hazard ratio [HR]: 1.37%; p = 0.04).<xref ref-type="bibr" rid="B118"><sup>118</sup></xref></p>
            <p>The Asymptomatic Carotid Trial (ACT) 1 study (n = 1,453) included patients with significant asymptomatic carotid disease, randomized into interventional treatment by CEA (n = 364; 25%) or CAS (n = 1,089; 75%). Elderly patients &gt; age and those who had suffered stroke/TIA during the past 180 days were excluded. The carotid anatomical pattern was required to be viable for both procedures, with a minimum degree of stenosis of 70% diagnosed by either ultrasonography or angiography.<xref ref-type="bibr" rid="B119"><sup>119</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B120"><sup>120</sup></xref></p>
            <p>The main objective was to demonstrate the noninferiority of CAS to CEA in relation to a composite endpoint, represented by death, AMI, and stroke during the first 30 days and ipsilateral stroke within 1 year. The results during 30 days showed that the incidence of this endpoint was only 2.95%. There were more cases of stroke and stroke or death in the CAS group and more cases of AMI in the CEA subgroup. The risk of major stroke was low (0.4%) and mortality was 0.2%. Medium- and long-term survival free of stroke was excellent in both groups, 97.5% over 1 year and 93.9% over 5 years. In 5 years, 97.5% of participants did not require carotid reintervention, and total mortality was 11.8%.<xref ref-type="bibr" rid="B119"><sup>119</sup></xref></p>
          </sec>
          <sec>
            <title>1.12.4. Precautions and Recommendations</title>
            <p>The main problem with interventional carotid treatment lies in the risk of death, AMI, or stroke inherent in the procedures per se, which extends to 30 days after intervention. Once this phase has passed, the annual risk of stroke or need for reintervention is considered low.</p>
            <p>Intervention by CEA or CAS in patients with asymptomatic carotid disease dos not have a solid base for recommendation in comparison with optimized clinical treatment, and it should preferably be avoided at this moment until studies currently underway help to definitively answer this important question (CREST 2 and ACST-2).<xref ref-type="bibr" rid="B121"><sup>121</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B123"><sup>123</sup></xref></p>
            <p>More than 90% of carotid interventions in the USA currently involve asymptomatic cerebrovascular patients. In Germany and Italy, these indexes are 60%; in Australia and Canada, 15%; and in Denmark, 0%.</p>
            <p>The annual risk of stroke in asymptomatic patients with significant carotid disease receiving only clinical treatment has reached values as low as 0.5%, or be it, the same index documented in the ACT-1 and the 5 and 10 year CREST studies.<xref ref-type="bibr" rid="B122"><sup>122</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B123"><sup>123</sup></xref></p>
            <p>Contrary to what has been admitted by some guidelines, it is here suggested that interventional carotid treatment be reserved for symptomatic patients (stroke/TIA over the past &lt; 6 months), and that it be indicated for asymptomatic patients only when the degree of stenosis is between 70% and 99% in spite of optimized clinical treatment, and when there is proof that a large cerebral area is at risk or plaque-related microembolism, obtained by imaging exams and cerebral blood flow evaluation.<xref ref-type="bibr" rid="B121"><sup>121</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B123"><sup>123</sup></xref></p>
          </sec>
        </sec>
        <sec>
          <title>1.13. Evaluation of Surgical Risk In Elderly Patients</title>
          <p>The elderly population is currently growing more than any other. For this reason, a significant increase has been observed in the number of surgical procedures in this age group. The number of surgical procedures in people over age 65 is estimated to be 4 times higher than in the younger population.<xref ref-type="bibr" rid="B124"><sup>124</sup></xref> The prevalence of symptomatic and asymptomatic CVD increases progressively with age, as shown in the results of many studies which suggest that age &#8805; 80 is an independent predictor of perioperatory complications and death in patients who undergo non-cardiac or cardiac surgery.<xref ref-type="bibr" rid="B125"><sup>125</sup></xref> Few studies, however, include elderly individuals over age 70 and the results are, generally, extrapolated from younger to older populations, ignoring the latter&#8217;s particularities.<xref ref-type="bibr" rid="B126"><sup>126</sup></xref></p>
          <p>Clinical evaluation in the elderly population should consider biological processes underlying so-called normative aging, such as physiological decrease in multiple organic functions which may cause inadequate responses to anesthetics, analgesics, and other substances administered and also lead to the appearance of cardiovascular complications, hemorrhagic or neuropsychiatric accidents, et al. It is mandatory to evaluate associated comorbidities and their repercussions on nutrition, overall functionality, independence, and healthy life expectancy, as well as all medication in use, in order both to prevent possible complications and to choose the most adequate procedure for each case.<xref ref-type="bibr" rid="B127"><sup>127</sup></xref></p>
          <p>As a general rule, the establishment of a patient&#8217;s surgical risk should be individualized and the bioethical principle of patient autonomy should be respected in all patient decisions or, in the event of impossibility, those of the patient&#8217;s legal representative, following adequate clarification regarding the risks inherent in the disease and the surgical procedure, during the intraoperative and immediate and late postoperative periods, and the quality of life expected to result from the treatment. It is necessary to document the patient&#8217;s and/or legal representative&#8217;s decision in the medical records.<xref ref-type="bibr" rid="B128"><sup>128</sup></xref></p>
          <p>With these considerations, surgical risk should be established based on a &#8220;tripod&#8221; comprising: (1) nature and character of the surgery; (2) functional capacity; (3) patient risk profile.</p>
          <p>The new guidelines have established that elective and minor surgeries where the possibility of heart attack or major adverse cardiovascular events is &#8804; 1% are low risk; when the possibility is &#8805; 1% they are considered high risk. More recent publications have incorporated intermediate or high risk.<xref ref-type="bibr" rid="B129"><sup>129</sup></xref> Patients indicated for urgent surgery should have their risks established when possible, using information provided by the family or the patients themselves, and then be referred to the surgical center. In the event of elective surgeries where the patient&#8217;s hemodynamic conditions are not stable, they must be treated before establishing status and choosing the most opportune moment to perform the operation.</p>
          <p>Patient functional capacity is a valuable indicator of risk of complications during the course of surgery and the postoperative period. The ability to ascend 2 stories by stairs or by ramp or to walk at a velocity of approximately 4 mph on a level surface corresponds to a metabolic equivalent (MET) &#8805; 4, which indicates a good cardiovascular reserve and regular physical capacity; MET &#8805; 10 is considered very good.</p>
          <p>The last step in this strategy is to establish the patient&#8217;s risk profile based on his or her clinical history, symptoms, signs, and laboratory data. In the presence of unstable coronary syndromes, decompensated HF, symptomatic valve disease, severe arrhythmias, or pulmonary embolisms which may compromise the course of the perioperative period, non-invasive exams are indicated in order to improve comprehension. When non-invasive exams are suggestive of coronary insufficiency, it is necessary to indicate scintigraphy stress testing, eventual coronary angiography, and even myocardial revascularization, provided that performing this may substantially change patient management or survival, taking the severity of the underlying disease into account.<xref ref-type="bibr" rid="B130"><sup>130</sup></xref></p>
        </sec>
        <sec>
          <title>1.14. Vaccination in Elderly Patients</title>
          <sec>
            <title>1.14.1. Brazilian Immunization Society (SBIm) Recommendations &#8211; 2015/2016<xref ref-type="bibr" rid="B131"><sup>131</sup></xref></title>
            <p><bold>Influenza</bold> [indicated for all elderly individuals] &#8211; Influenza is a highly infectious acute respiratory infection, caused by <italic>Myxovirus influenzae</italic>, a virus that is not specific to humans (The virus infects different domestic and wild vertebrates which may, in turn, infect humans). There are 3 known types, A, B, and C, and there is no crossed immunity between them. Type A is the most virulent. It causes the largest epidemics, and is subdivided into subtypes in accordance with the characteristics of its superficial molecules (designated by the abbreviations HA and NA). There are currently 2 subtypes of influenza A in circulation among humans: H1N1 and H3N2.</p>
            <p>The mortality associated with this virus may be elevated in more elderly and very young individuals, as well as in those with respiratory, cardiovascular, or renal pathologies, or diabetes, for example. The severity of the illness may be due to the virus itself or, more frequently, overlapping bacterial infections that follow influenza. There are 2 types of influenza vaccine, trivalent (3V) and quadrivalent (4V). The 3V protects against the H1N1 and H3N2 strains (both influenza A) and against a 1 type of the influenza B virus. The 4V protects against the forenamed strains and, additionally, against a second influenza B virus. Provided that it is available, the 4V influenza vaccine is preferable to the 3V, as it provides greater protection against circulating strains. If it is not possible to use the 4V vaccine, the 3V vaccine should be used. The vaccine offered by the public system is the 3V. Contraindications include known systemic hypersensitivity to any medication or substance, including neomycin, formaldehyde, triton-X-100 (octoxinol 9), eggs, or chicken protein, either following the administration of this vaccine or a vaccine containing the same composition. People with acute febrile diseases should not, normally, be vaccinated until these symptoms have disappeared.</p>
            <p><bold>Pneumococcal vaccine</bold> [indicated for all elderly individuals] &#8211; This vaccine protects against invasive infections (sepsis, meningitis, pneumonia, and bacteremia) and acute otitis media (AOM), caused by some serotypes of <italic>Streptococcus pneumoniae</italic>. It starts with a dose of VPC13, followed by a dose of VPP23 6 to 12 months later, and a second dose of VPP23, 5 years after the first. For those who have already received VPP23, an interval of 1 year is recommended for the application of VPC13. A second dose of VPP23 should be given 5 years after the first, maintaining an interval of 6 to 12 months after the dose of VPC13. For those who have already received 2 doses of VPP23, a dose of VPC13 is recommended at a minimal interval of 1 year after the latest dose of VPP23. If the second dose of VPP23 was applied before age 65, a third dose is recommended after this age, with a minimum interval of 5 years after the latest dose. This vaccine is available through the public system for risk groups (COPD, diabetes, etc.)</p>
            <p><bold>Diphtheria, tetanus, and acellular pertussis (DTaP)/diphtheria and tetanus (DT)</bold> [indicated for all elderly patients] &#8211; This vaccine protects against diphtheria, tetanus, and acellular pertussis (DTaP) or diphtheria and tetanus (DT). A DTaP booster is necessary, regardless of previous DT or tetanus interval. For elderly patients who intend to travel to countries where polio is endemic, the combined DTaP inactivated poliovirus vaccine (DTaP-IPV) is recommended. The combined DTaP-IPV vaccine may substitute the DTaP. When the basic vaccination schedule for tetanus is complete, a DTaP booster is recommended every 10 years. When the basic vaccination scheme for tetanus is incomplete, a DTaP dose is recommended at any moment, completing basic vaccination with 1 or 2 doses of adult DT vaccine, in a manner that totals 3 doses of tetanus vaccine. This vaccine is recommended, even in individuals who have already had pertussis, given that protection provided by the infection is not permanent. It is possible to consider anticipating a DTaP booster, containing the pertussis component, to 5 years after the latest dose in elderly individuals who are in contact with breastfeeding infants. The DT is available through the public system.</p>
            <p><bold>Herpes zoster</bold> [indicated for all elderly patients] &#8211; This vaccine is recommended even in patients who have already had herpes zoster. In these cases, a minimum interval of 1 year is necessary between the acute phase and the vaccine application. In cases of patients with a history of ophthalmic herpes zoster, there are still not enough data to indicate or contraindicate the vaccine. Regarding use in immunocompromised patients, the vaccine should not be used in individuals with primary or acquired immunodeficiency states or those undergoing drug therapy at doses considered immunosuppressive. This vaccine is not available through the public system.</p>
          </sec>
          <sec>
            <title>1.14.2. Other Vaccines (Non-Routine)</title>
            <p><bold>Hepatitis A, B, or A+B</bold> &#8211; Hepatitis A: 2 doses, in 0 and 6 month schedule. Hepatitis B: 3 doses, 0, 1, and 6 month schedule. Hepatitis A and B: 3 doses, 0, 1, and 6 month schedule. For hepatitis A, in the over 60 population, susceptible individuals are not commonly found. Vaccination is, thus, not a priority in this group. Serology may be requested in order to determine whether or not to vaccinate. In patients who have contact with hepatitis A or during an outbreak of the disease, vaccination should be considered. Regarding hepatitis A, B, and A+B, the combined hepatitis A and B vaccine is an option, and it may substitute isolated vaccination for hepatitis A and B.</p>
            <p><bold>Yellow fever</bold> &#8211; The vaccine is necessary in residents of risk areas and in those who intend to travel to these areas, at least 10 days before travel. If the risk persists, 10 years later, a second dose is necessary. This vaccine is contraindicated in immunocompromised individuals; however, when the risks of acquiring the disease outweigh the potential risks associated with vaccination, the physician should evaluate its use. There are reports of a higher risk of serious adverse events in patients over 60 years of age; therefore, if it is the primary vaccination, it is necessary to assess the risk-benefit ratio.</p>
            <p><bold>Measles, mumps, and rubella</bold> &#8211; Individuals are considered protected when they have, at some point in their lives, over 1 year of age, received 2 doses of the measles, mumps, and rubella vaccine with a minimum interval of 1 month between them. The vaccine is indicated in increased risk situations, given that the majority of people in this age group are not susceptible to these diseases. In the over 60 population, individuals susceptible to measles, mumps, and rubella are not commonly found. In this group, vaccination is thus, not routine. Nonetheless, according to medical criteria (during outbreaks, before travel, et al.), it may be recommended. It is contraindicated in immunocompromised individuals.</p>
          </sec>
        </sec>
        <sec>
          <title>1.15. Palliative Care</title>
          <p>Palliative care (PC), which was initially focused on oncology, has been incorporated into diverse practice areas, one of which is cardiology, with discussions on PC in the area of CVD, especially involving the most elderly population. For this reason, this topic deserves to be covered in this document.</p>
          <p>According to the WHO, PC is defined as a mode of assistance provided by a multidisciplinary team with the objective of improving patient and family member quality of life, when faced with a life-threatening disease, through prevention and relief of suffering.<xref ref-type="bibr" rid="B132"><sup>132</sup></xref> PC requires early identification, evaluation, and treatment of pain and other physical, social, psychological, and spiritual issues.<xref ref-type="bibr" rid="B132"><sup>132</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B133"><sup>133</sup></xref></p>
          <p>PC should be individualized; it is not an approach to &#8220;terminal&#8221; patients, but rather to a life-threatening clinical condition.<xref ref-type="bibr" rid="B133"><sup>133</sup></xref> Its indication should be early, at the moment of diagnosis, in a manner that promotes understanding, acceptance, and progressive expansion of the means of support over time. The possibility of whether or not to implement disease-modifying treatments should be discussed in a manner that does not allow for the idea that &#8220;there&#8217;s nothing to do.&#8221;<xref ref-type="bibr" rid="B133"><sup>133</sup></xref></p>
          <p>The principles that guide PC in accordance with the WHO consist of:<xref ref-type="bibr" rid="B132"><sup>132</sup></xref></p>
          <list list-type="order">
            <list-item>
              <p>Relieve pain and other distressing physical symptoms.</p>
            </list-item>
            <list-item>
              <p>Affirm life and consider death as a normal life process.</p>
            </list-item>
            <list-item>
              <p>Neither hasten nor postpone death.</p>
            </list-item>
            <list-item>
              <p>Integrate psychological and spiritual aspect into patient care.</p>
            </list-item>
            <list-item>
              <p>Offer a support system that makes it possible for the patient to live as actively as possible, until the moment of death.</p>
            </list-item>
            <list-item>
              <p>Offer a support system that helps family members cope with the disease and bereavement.</p>
            </list-item>
            <list-item>
              <p>Improve quality of life and positively influence the course of the disease.</p>
            </list-item>
            <list-item>
              <p>Initiate care as early as possible, in conjunction with other life-prolonging measures, such as chemotherapy and radiotherapy, and include all necessary investigations to better comprehend and control existing clinical situations.</p>
            </list-item>
          </list>
          <p>From the theoretical point of view, all patients with serious, incurable, and progressive diseases that are life-threatening should receive PC.<xref ref-type="bibr" rid="B133"><sup>133</sup></xref> If this reference were put into practice, the number of patients indicated for PC would be enormous, and it would not be possible to provide this type of assistance to all of them. For this reason, the National Academy of Palliative Care (Academia Nacional de Cuidados Paliativos, ANCP)<xref ref-type="bibr" rid="B133"><sup>133</sup></xref> recommends the adoption of the criteria used by Medicare in the United States,<xref ref-type="bibr" rid="B134"><sup>134</sup></xref> which establishes expected survival time as a criterion for indicating PC. Adapting the Medicare criteria, we may suggest the following conditions for indicating PC:<xref ref-type="bibr" rid="B133"><sup>133</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B134"><sup>134</sup></xref></p>
          <list list-type="order">
            <list-item>
              <p>Patient with life expectancy less than or equal to 6 months.</p>
            </list-item>
            <list-item>
              <p>Diagnosis with an incurable and irreversible disease.</p>
            </list-item>
            <list-item>
              <p>The patient must opt for PC, giving up life-prolonging treatments.</p>
            </list-item>
            <list-item>
              <p>The implementation of PC should be operationally available.</p>
            </list-item>
          </list>
          <p>Prognostic evaluation of patients receiving PC is a complex process involving physiological and social judgments. The ANCP recommends some instruments for evaluating patient functionality, as well as measuring functional and clinical decline, such as the Karnofsky Performance Status Scale and the Palliative Performance Scale. These scales and their methods of evaluation are detailed in the ANCP&#8217;s Palliative Care Manual, which is available on their virtual library (<ext-link ext-link-type="uri" xlink:href="http://paliativo.org.br/">http://paliativo.org.br/</ext-link>).<xref ref-type="bibr" rid="B133"><sup>133</sup></xref></p>
          <p>In relation to CVD, they are known to be the main cause of death in Brazil, as well as in other parts of the world. They may occur at any age, but their prevalence is higher with advanced age.<xref ref-type="bibr" rid="B133"><sup>133</sup></xref> Among CVD, HF represents a challenge to prognostic evaluation, given that many patients die suddenly, even when they are in higher functional classes. Diverse criteria have sought to identify patients with HF at a risk of sudden death, such as left ventricular ejection fraction (LVEF), type B natriuretic peptide, end-diastolic LV diameter, presence of nonsustained ventricular tachycardia, diabetes mellitus, thromboembolic phenomena, history of previous cardiorespiratory arrest, and AIDS diagnosis.<xref ref-type="bibr" rid="B133"><sup>133</sup></xref> The difficulty of prognosis in patients with HF makes it challenging to discuss care preferences with patients; for this reason, these patients have been considered those with the least comprehension of their clinical condition and the least involved in the decision making process related to their care.<xref ref-type="bibr" rid="B133"><sup>133</sup></xref> Patients with CVD suffer severely, and they are among those who least receive home healthcare and PC; for this reason, these Guidelines agree with the idea that PC should be considered earlier during the evolutionary course of CVD and in routine cardiology practice.</p>
        </sec>
      </sec>
      <sec>
        <title>2. Chronic Coronary Disease</title>
        <sec>
          <title>2.1. Peculiarities of Diagnosing Chronic Coronary Artery Disease in Elderly Patients</title>
          <p>Clinical history and detailed physical examination are essential when evaluating an elderly patient with suspected chronic CAD; however, in routine practice, this constitutes a challenge, considering the occurrence of comorbidities, atypical symptoms, and alterations in cognition and locomotion.</p>
          <p>Ischemia is frequently present in the form of anginal equivalents, such as fatigue, dyspnea, and epigastric discomfort, with the presence of typical angina being rare.<xref ref-type="bibr" rid="B135"><sup>135</sup></xref> Physical examination, generally non-specific, may provide some leads, such as SAH, abnormal heart rhythms such as atrial fibrillation (AF), and peripheral arterial disease.</p>
          <p>Resting EKG may be non-specific in 50% of cases, even in those with severe coronary disease;<xref ref-type="bibr" rid="B136"><sup>136</sup></xref> alterations such as pathological Q waves, T-wave inversions, left ventricular hypertrophy (LVH), His bundle branch blocks, and AF are common in elderly patients. These alterations complicate diagnosis. EKG is particularly useful during episodes of angina, when ST segment depression or pseudonormalization may be observed in up to 50% of cases.</p>
          <p>Chest radiography should be performed when there is a suspected coexistence of congestive HF, valvulopathy, or respiratory disease.</p>
          <p>Transthoracic echocardiography provides information which is relevant to diagnosis and management of chronic: (a) LV status &#8211; systolic and diastolic function, parietal mobility, and hypertrophy; (b) presence of valvulopathy; (c) situation of the aortic root.</p>
          <p>The use of functional tests for ischemia (ET, stress echocardiography and myocardial perfusion scintigraphy [MPS]) or anatomical tests (coronary computed tomography angiography [CCTA] and coronary cine angiogram [CCA]) depends on pre-test estimates on the likelihood of obstructive CAD.<xref ref-type="bibr" rid="B137"><sup>137</sup></xref> When the probability is low (&lt; 20%), it is not necessary to continue investigation. On the other hand, when the probability is high, (&gt; 80%), negative results of non-invasive exams cannot exclude obstructive CAD; invasive strategies may, thus, be considered. In patients with intermediate pre-test probability, a stress test is indicated.</p>
          <p>In elderly patients, the diagnostic sensitivity and specificity of ET have been questioned,<xref ref-type="bibr" rid="B138"><sup>138</sup></xref> as a result of low exercise capacity (reduced muscle mass, deconditioning, comorbidities) and the presence of alterations in baseline EKG; nevertheless, this method may be useful in clinical management, offering relevant information on symptoms, exercise capacity, chronotropic response, arrhythmias, etc.</p>
          <p>Both stress tests and MPS may be used in association with the ET to increment sensitivity and specificity for ischemia.<xref ref-type="bibr" rid="B139"><sup>139</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B140"><sup>140</sup></xref> Diagnosis and prognosis of both modalities are similar and the preference for a determined method depends on the experience and/or equipment available at the investigating center. For elderly patients incapable of exercising, pharmacological stress may be used both in the stress test (dobutamine) and the MPS (vasodilatory agents).</p>
          <p>The CCS, obtained in conjunction with CCTA, is useful for risk stratification in asymptomatic elderly patients, due to its high negative predictive value;<xref ref-type="bibr" rid="B141"><sup>141</sup></xref> its value, however, is limited in symptomatic patients with suspected CAD. Due to the high prevalence of coronary calcification in the elderly, CCTA has shown to be of reduced accuracy in demonstrated obstructive CAD.<xref ref-type="bibr" rid="B142"><sup>142</sup></xref></p>
          <p>CCA continues to be the &#8220;gold standard&#8221; for definitive evaluation of epicardial CAD; it is generally recommended for patients whose clinical characteristics and/or non-invasive test results indicate a high likelihood of severe coronary disease, with a high risk of coronary events or death. Even though it is well tolerated, it deserves attention due to the risk of bleeding, stroke, and contrast-induced nephropathy.</p>
        </sec>
        <sec>
          <title>2.2. Peculiarities of Treating Chronic Coronary Artery Disease In Elderly Patients</title>
          <p>During the last decades, the treatment of coronary disease has been founded on general clinical measures related to the development of healthy habits, such as a balanced diet, weight control, regular practice of physical activity, vaccination schedule completion, tobacco cessation, intensive BP control, and appropriate use of antiatherosclerotic medications such as statins, antiplatelet medications, and renin-angiotensin system inhibitors, in addition to antianginal agents.<xref ref-type="bibr" rid="B143"><sup>143</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B145"><sup>145</sup></xref> Additionally, well selected cases are treated with myocardial revascularization procedures, through percutaneous coronary intervention or surgery. In elderly patients, these principles are largely applicable with evidence which it has been possible to extrapolate from randomized clinical trials, that have begun to include &#8220;young&#8221; elderly individuals (ages 60 to 75) in their observations, with less frequently evaluation of &#8220;truly elderly&#8221; individuals (ages 75 to 85) are scarce evaluation of &#8220;very elderly&#8221; individuals (over age 85).<xref ref-type="bibr" rid="B143"><sup>143</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B145"><sup>145</sup></xref></p>
          <p>Regarding diet, the Lyon, Dietary Approaches to Stop Hypertension (DASH), and, more recently, <italic>Prevenci&#243;n con Dieta Mediterr&#225;nea</italic> (PREDIMED) studies have validated the concept of a healthy diet; the PREDIMED included patients up to age 80. Weight control represents a particular consideration in the elderly owing to the apparent existence of a paradox between BMI and age.<xref ref-type="bibr" rid="B146"><sup>146</sup></xref> In a more conclusive analysis of the topic of CAD, the reduction of obesity is associated with better results.</p>
          <p>Regular practice of activities which are appropriate for the elderly individual&#8217;s physical conditions bring innumerable psychological benefits that impact improvements in general healthcare and which justify their implementation.</p>
          <p>Inflammation caused by infections plays a recognized role on the emergence of coronary disease complications, and influenza and pneumococcal vaccination is a recommendable measure in elderly coronary disease patients.<xref ref-type="bibr" rid="B147"><sup>147</sup></xref></p>
          <p>Analysis of the Coronary Artery Study (CASS) registry has been definitive in demonstrating the benefits of tobacco cessation in elderly coronary disease patients.<xref ref-type="bibr" rid="B148"><sup>148</sup></xref></p>
          <p>A systolic blood pressure (SBP) control goal of &lt; 140 mmHg has been established for the elderly population. A recent study, the Systolic Blood Pressure Intervention Trial (SPRINT), recommends that this goal be even more intensive, even in elderly coronary disease patients (&lt; 130 mmHg, if tolerated), without verifying the J curve or undesired events in relation to reduced diastolic BP. Special caution needs to be taken in this population when comorbidities are present.<xref ref-type="bibr" rid="B149"><sup>149</sup></xref></p>
          <p>Antiatherosclerotic medications such as statins have confirmed demonstration, in clinical trials, up to age 79. If tolerated, they should be used to stimulate an LDL-c goal of &lt; 70 mg/dL. Acetylsalicylic acid (ASA) is recommended, as well as the use of angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), even in the absence of SAH or HF, notwithstanding the fact that both of these conditions are frequently associated with CAD in the elderly.</p>
          <p>Anti-ischemic medications, such as beta-blockers (and calcium channel blockers, when beta-blockers are not possible, or in association with them) for control and nitrates for crises, as well as new anti-ischemic medications, such as trimetazidine, should be used with due caution regarding progressive doses, due to the higher incidence of side effects. Ivabradine may be considered for HR control when it is not possible to use beta-blockers.<xref ref-type="bibr" rid="B150"><sup>150</sup></xref></p>
          <p>In relation to revascularizing elderly patients without frailty by either percutaneous or surgical intervention, this should be considered with the aim of controlling refractory symptoms or in cases with severe ischemic burden. With respect to deciding which procedure should be performed, whether percutaneous intervention or surgery, this depends wholly on the feasibility of using the techniques, it being necessary to consider that age adds a considerable weight to risk of both procedures and that scores that include associated comorbidities tend to affect the surgical procedure even more.<xref ref-type="bibr" rid="B151"><sup>151</sup></xref></p>
          <p>In conclusion, in addition to the previously mentioned facts, therapeutic recommendations must consider many other relevant factors such as biological aspects of frailty, psychological competence, economic and social support, among others. This makes this choice an optimal example of personalized therapy centered on the elderly individual who is affected by CAD.</p>
          <p>2.3. General Recommendations &#8211; Chronic Coronary Artery Disease in Elderly Patients</p>
          <table-wrap id="t57">
            <table frame="hsides" rules="groups">
              <colgroup width="20%">
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top" colspan="5">Diagnostic evaluation of chronic coronary disease in elderly patients</th>
                </tr>
                <tr>
                  <th align="left" valign="top">Method</th>
                  <th align="center" valign="top">Positive aspects</th>
                  <th align="center" valign="top">Possible limitations</th>
                  <th align="center" valign="top">Grade of recommendation</th>
                  <th align="center" valign="top">Level of evidence</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">EKG</td>
                  <td align="center" valign="top">Easily obtained. Detection of inactive zones and conduction disorders</td>
                  <td align="center" valign="top">Low accuracy</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Ergometric test</td>
                  <td align="center" valign="top">Availability. Moderate accuracy in detecting ischemia</td>
                  <td align="center" valign="top">Locomotive difficulties. Resting EKG alterations</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Stress echocardiography (exercise, dobutamine, or dipyridamole)</td>
                  <td align="center" valign="top">Detection and evaluation of the extent of ischemia. Evaluation of LV function</td>
                  <td align="center" valign="top">Echocardiography window. Cost</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Scintigraphy</td>
                  <td align="center" valign="top">Detection and evaluation of the extent of ischemia. Does not depend on preexisting electrocardiographic alterations. Evaluation of LV function</td>
                  <td align="center" valign="top">Lower availability. Cost</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Coronary computed tomography angiography</td>
                  <td align="center" valign="top">Detection of obstructions</td>
                  <td align="center" valign="top">Calcification in the elderly patient decreases diagnostic accuracy</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Coronary magnetic resonance angiography</td>
                  <td align="center" valign="top">Detection of obstructions</td>
                  <td align="center" valign="top">Lower accuracy. Difficult to obtain</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Cardiac magnetic resonance</td>
                  <td align="center" valign="top">LV function. Areas of fibrosis</td>
                  <td align="center" valign="top">Difficult to obtain</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN26a">
                <p><italic>EKG: electrocardiogram; LV: left ventricle</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <table-wrap id="t58">
            <table frame="hsides" rules="groups">
              <colgroup width="50%">
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top" colspan="2">Treatment of chronic coronary disease in elderly patients</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top" rowspan="6">General measures</td>
                  <td align="center" valign="top">&#9679; Balanced diet</td>
                </tr>
                <tr>
                  <td align="center" valign="top">&#9679; Weight control</td>
                </tr>
                <tr>
                  <td align="center" valign="top">&#9679; Regular practice of physical activity</td>
                </tr>
                <tr>
                  <td align="center" valign="top">&#9679; Vaccination schedule completion</td>
                </tr>
                <tr>
                  <td align="center" valign="top">&#9679; Tobacco cessation</td>
                </tr>
                <tr>
                  <td align="center" valign="top">&#9679; Intensive blood pressure control</td>
                </tr>
                <tr>
                  <td align="left" valign="top" rowspan="3">Antiatherosclerotic medications</td>
                  <td align="center" valign="top">&#9679; Statins</td>
                </tr>
                <tr>
                  <td align="center" valign="top">&#9679; Antiplatelets</td>
                </tr>
                <tr>
                  <td align="center" valign="top">&#9679; Renin-angiotensin system inhibitors (ACEI/ARB)</td>
                </tr>
                <tr>
                  <td align="left" valign="top" rowspan="4">Antianginal medications</td>
                  <td align="center" valign="top">&#9679; Beta-blockers</td>
                </tr>
                <tr>
                  <td align="center" valign="top">&#9679; Calcium channel blockers</td>
                </tr>
                <tr>
                  <td align="center" valign="top">&#9679; Nitrates</td>
                </tr>
                <tr>
                  <td align="center" valign="top">&#9679; Trimetazidine</td>
                </tr>
                <tr>
                  <td align="left" valign="top" rowspan="2">Myocardial revascularization</td>
                  <td align="center" valign="top">&#9679; Percutaneous coronary intervention</td>
                </tr>
                <tr>
                  <td align="center" valign="top">&#9679; Myocardial revascularization surgery</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN27a">
                <p><italic>ACEI: angiotensin converting enzyme inhibitors; ARB: angiotensin receptor blockers</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <table-wrap id="t59">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top" colspan="3">Recommendations for general measures and antiatherosclerotic use</th>
                </tr>
                <tr>
                  <th align="left" valign="top">Procedure/medication</th>
                  <th align="center" valign="top">Grade of recommendation</th>
                  <th align="center" valign="top">Level of evidence</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Balanced diet</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Weight control</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Physical activity</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Vaccination against influenza</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Tobacco cessation</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top">BP control &lt; 140 mmHg</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top">BP control &lt; 120 mmHg</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Statins</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Antiplatelets</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top">ACEI/ARB</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN28a">
                <p><italic>ACEI: angiotensin converting enzyme inhibitors; ARB: angiotensin receptor blockers. BP: blood pressure</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <table-wrap id="t60">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top" colspan="3">Recommendations for antianginal medications</th>
                </tr>
                <tr>
                  <th align="left" valign="top">Medication</th>
                  <th align="center" valign="top">Grade of recommendation</th>
                  <th align="center" valign="top">Level of evidence</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Beta-blockers</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Calcium channel blockers</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Nitrates for anginal crises</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Nitrates for chronic use</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Trimetazidine</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Ivabradine</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">B</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
          <table-wrap id="t61">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top" colspan="3">Indication for revascularization in elderly patients refractory to clinical treatment</th>
                </tr>
                <tr>
                  <th align="left" valign="top">PCI &#8211; Patients with angina</th>
                  <th align="center" valign="top">Grade of recommendation</th>
                  <th align="center" valign="top">Level of evidence</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">PCI feasible and easily applied</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Low SYNTAX score</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">High SYNTAX score</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">
                    <bold>Surgery &#8211; Patients com angina</bold>
                  </td>
                  <td align="center" valign="top">
                    <bold>Grade of recommendation</bold>
                  </td>
                  <td align="center" valign="top">
                    <bold>Level of evidence</bold>
                  </td>
                </tr>
                <tr>
                  <td align="left" valign="top">Multivascular, with low surgical risk</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Low SYNTAX score and moderate to high surgical risk</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">B</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN29a">
                <p><italic>PCI: percutaneous intervention; SYNTAX: Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <table-wrap id="t62">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top" colspan="3">Indication for revascularization in asymptomatic elderly patients</th>
                </tr>
                <tr>
                  <th align="left" valign="top">Severe ischemic load</th>
                  <th align="center" valign="top">Grade of recommendation</th>
                  <th align="center" valign="top">Level of evidence</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Percutaneous intervention</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Surgery</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
        </sec>
      </sec>
      <sec>
        <title>3. Acute Coronary Disease</title>
        <sec>
          <title>3.1. Diagnostic Peculiarities</title>
          <p>Elderly patients have a higher incidence of acute coronary syndrome (ACS), and their prognosis is worse in comparison with younger patients. The causes of this unfavorable evolution include: (a) delayed arrival at the hospital; (b) diagnostic difficulties; (c) lower likelihood of receiving interventional treatment; (d) less use of beta-blockers; (e) previous HF; and (f) comorbidities.<xref ref-type="bibr" rid="B152"><sup>152</sup></xref> As age increases, the effects of risk factors such as hypertension, diabetes, and tobacco use decreases, and the importance of associated comorbidities, such as stroke and renal and cardiac insufficiency increases.<xref ref-type="bibr" rid="B153"><sup>153</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B154"><sup>154</sup></xref> Atypical presentation is more common in this age group; chest pain is present in 40% of patients &#8805; age 80, compared to 80% in those &#8804; age 65. In elderly heart attack patients, 8.4% do not present precordial pain (43.3% in patients &#8805; 75 years old, compared to 29.4% in those &#8804; 65 years old). More common symptoms include: dyspnea (29.4%), sweating (26.2%), nausea and vomiting (24.3%), and syncope and pre-syncope (19.1%), which are denominated ischemic equivalents.</p>
          <p>Although physical examination may be normal, the presence or absence of signs of peripheral hypoperfusion, vital signs, presence or absence of arterial pulses, jugular vein distention, cardiac auscultation (blowing, friction, third heart sound), and pulmonary auscultation with signs of congestion are important data to evaluate. Initial EKG is less solicited and more delayed, in elderly patients: 40% of patients &#8805; age 85, compared to 25% of those &#8804; age 65, do not have diagnostic EKG. The presence of non-specific EKG alterations and blocks is more frequent in elderly patients, increasing diagnostic difficulties in this age group, especially in the presence of left bundle branch block.<xref ref-type="bibr" rid="B102"><sup>102</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B155"><sup>155</sup></xref> Elevated myocardial necrosis markers unrelated to ACS are common in other situations, such as increased plasma N-terminal brain natriuretic propeptide (NT-pro-BNP), diabetes, renal insufficiency, anemia, dehydration, metabolic and hydroelectrolytic disorders, infections, and echocardiography abnormalities in chronic heart diseases.<xref ref-type="bibr" rid="B156"><sup>156</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B159"><sup>159</sup></xref></p>
          <p>Risk scores, such as the Thrombolysis in Myocardial Infarction (TIMI) Risk<xref ref-type="bibr" rid="B160"><sup>160</sup></xref> and the Global Registry of Acute Coronary Events (GRACE),<xref ref-type="bibr" rid="B161"><sup>161</sup></xref> are important for risk stratification of elderly ACS patients, ensuring better strategy in diagnostic and therapeutic approach, increasing the use of antithrombotic and anticoagulant medications and myocardial revascularization, with a consequent decrease in risk of death, heart attack, and recurring ischemia.<xref ref-type="bibr" rid="B162"><sup>162</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B163"><sup>163</sup></xref> Being over age 70 confers a moderate (ages 70 to 75) to high (&gt; age 75) risk of coronary disease.</p>
          <p>Frailty is an important independent predictor of mortality, longer hospital stays, increased risk of bleeding and morbidity in the elderly population with ACS.<xref ref-type="bibr" rid="B164"><sup>164</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B165"><sup>165</sup></xref> Functional decline in elderly patients is a predictor of poor evolution.<xref ref-type="bibr" rid="B166"><sup>166</sup></xref> The Gold Standards Framework (GSF) score, which associates end-stage disease criteria, has shown to be an independent predictor of non-cardiovascular events in ACS, while the GRACE score has demonstrated that it is an excellent predictor of cardiovascular events in elderly patients.<xref ref-type="bibr" rid="B167"><sup>167</sup></xref> Chest radiography, resting transthoracic echocardiography, myocardial scintigraphy, coronary angiotomography, cardiac magnetic resonance, and CCA follow the same indications as in younger patients for diagnosis of ACS in this age group.<xref ref-type="bibr" rid="B156"><sup>156</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B157"><sup>157</sup></xref></p>
        </sec>
        <sec>
          <title>3.2. Peculiarities of Treatment</title>
          <p>Even though the elderly population is the one that most benefits from more aggressive strategies, they have a higher risk of bleeding, with a 2-fold risk of mortality compared to younger patients (&lt; 75 years old). Higher intra-hospital mortality and higher bleeding rates with thrombolytic therapy are part of this scenario. Approach to ACS in elderly patients should be individualized, based on risk of complications, estimated life expectancy, comorbidities, quality of life, and the patient&#8217;s wishes and preferences.<xref ref-type="bibr" rid="B153"><sup>153</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B154"><sup>154</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B156"><sup>156</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B157"><sup>157</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B168"><sup>168</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B170"><sup>170</sup></xref> Elderly patients (&gt; age 75) with acute coronary syndrome with ST-segment elevation (ACS-STE) and without ST-segment elevation (ACS-NSTE) should follow the same diagnostic and therapeutic approach as in younger patients, based on guidelines and consensuses, it being necessary to evaluate particularities of pharmacokinetics, sensitivity, and collateral effects and collateral effects of drugs, always taking weight and creatinine clearance into account.<xref ref-type="bibr" rid="B102"><sup>102</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B153"><sup>153</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B154"><sup>154</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B156"><sup>156</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B157"><sup>157</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B168"><sup>168</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B170"><sup>170</sup></xref></p>
          <p>During the past 15 years, there has been a significant increase in the rates of pharmacological therapy use based on evidence for ACS patients in all age groups. However, in cases of ACS-STE, elderly patients have a lower chance of receiving primary angioplasty or thrombolysis, as well as the prescription of ASA, clopidogrel, beta-blockers, statins, or ACEI.<xref ref-type="bibr" rid="B171"><sup>171</sup></xref> The Study of Global Ageing and Adult Health (SAGE) compared the effects of intensive (atorvastatin 80 mg) versus moderate statin therapy (pravastatin 40 mg) on reducing myocardial ischemia in elderly patients between the ages of 65 and 85. Both statin regimens were equally effective in reducing the frequency and duration of ischemia; intensive therapy with atorvastatin, however, was demonstrated to be more effective in the reduction of lipids and all-cause mortality, in comparison with pravastatin.<xref ref-type="bibr" rid="B170"><sup>170</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B172"><sup>172</sup></xref> However, due to the prevalence of collateral effects and intolerance to this medication in this age range, lower doses of statins are suggested for ACS patients, until LDL-c &lt; 70 mg/dL has been reached, maintaining the tolerated dose.</p>
          <p>After age 85, studies suggest that there are benefits associated with reperfusion strategies for ACS-STE. The choice between fibrinolytic drugs and angioplasty is determined by the presence or absence of cardiogenic shock, presentation time, and comorbidities, which often tend toward angioplasty in elderly patients. The safety and efficacy of reperfusion, especially fibrinolytic therapy, in very elderly patients (&#8805; 85 years old) are questions which require deeper investigation.<xref ref-type="bibr" rid="B173"><sup>173</sup></xref> The After Eighty study investigators evaluated 457 patients over the age of 80 with ACS-NSTE (AMI and unstable angina) who were randomized to an invasive or a conservative strategy, suggesting that invasive therapy is superior, with a higher incidence of death, myocardial infarction, and stroke in the conservative therapy group. The same results were obtained in the subgroup of elderly patients over age 90.<xref ref-type="bibr" rid="B174"><sup>174</sup></xref></p>
        </sec>
        <sec>
          <title>3.3. General Recommendations &#8211; Acute Coronary Syndrome in Elderly Patients</title>
          <p>With elderly ACS patients, cardiologists face the following 3 challenges:</p>
          <table-wrap id="t63">
            <table frame="hsides" rules="groups">
              <colgroup width="100%">
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top">1<sup>st</sup> Challenge: summary of diagnostic challenges in elderly patients</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Atypical presentation: less typical pain and more anginal equivalents (dyspnea, syncope, stroke, HF, etc.)</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Greater severity: present with more HF and cardiogenic shock</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Higher prevalence of morbimortality: reinfarction, stroke, more severe hemorrhage, and death</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Lower effects of risk factors and greater importance of comorbidities</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Non-specific EKG in 43% of elderly patients &gt; 85 years old</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Myocardial infarction (ACS-STE) should be strongly suspected in women, diabetes patients, and elderly patients with atypical symptoms</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Due to frequent atypical presentation, elderly patients (&gt; 75 years old) should be investigated for ACS-NSTE with a lower level of suspicion</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
          <table-wrap id="t64">
            <table frame="hsides" rules="groups">
              <colgroup width="100%">
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top">2<sup>nd</sup> Challenge: summary of challenges regarding approach individualization</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Heterogeneous population</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Moderate to high risk in the most utilized risk stratification scores (TIMI, GRACE)</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Treatment should consider overall health, comorbidities, cognitive status, life expectancy, frailty, patient&#8217;s wishes and preferences</td>
                </tr>
                <tr>
                  <td align="left" valign="top">It is necessary to pay attention to pharmacokinetic alterations and sensitivity to hypotensive drugs</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
          <table-wrap id="t65">
            <table frame="hsides" rules="groups">
              <colgroup width="100%">
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top">3<sup>rd</sup> Challenge: summary of treatment challenges</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Treat elderly patients (&#8805; 75 years old) with medical therapy, early invasive strategy, and revascularization, as indicated, in accordance with guidelines</td>
                </tr>
                <tr>
                  <td align="left" valign="top">It is necessary to pay attention to adjustments in doses of antithrombotic drugs in elderly patients and patients with renal insufficiency</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Antithrombotic treatment should be adapted in accordance with weight and creatinine clearance</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Intensive medication strategies and revascularization intervention strategies should always be considered, observing the adverse effects of these therapies</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Adjustments in doses of beta-blockers, ACEI, ARB, and statins should be considered, with the aim of decreasing or avoiding collateral effects</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Consider invasive strategies and, if appropriate, revascularization, following careful evaluation of potential risks and benefits, estimated life expectancy, comorbidities, quality of life, frailty, and patient preferences</td>
                </tr>
                <tr>
                  <td align="left" valign="top">It is reasonable to choose myocardial revascularization surgery over angioplasty in more elderly patients, especially those with diabetes or multiple vessel disease, due to increased survival and reduction of cardiovascular events</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN30a">
                <p><italic>ACEI: angiotensin converting enzyme inhibitors; ACS-NSTE: acute coronary syndrome without ST-segment elevation; ACS-STE: acute coronary syndrome with ST-segment elevation; ARB: angiotensin receptor blockers; GRACE: Global Registry of Acute Coronary Events; HF: heart failure; TIMI: Thrombolysis in Myocardial Infarction</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
      </sec>
      <sec>
        <title>4. Heart Failure</title>
        <sec>
          <title>4.1. Diagnostic Peculiarities of Heart Failure in Elderly Patients</title>
          <p>Elderly patients may have atypical presentations of HF due to cognitive alterations, sedentarism, functional limitations, and the presence of comorbidities. These factors contribute to late diagnosis, thus making complementary exams important (<xref ref-type="fig" rid="f3">Figure 1</xref>).<xref ref-type="bibr" rid="B175"><sup>175</sup></xref> The use of biomarkers, such as outpatient values of brain natriuretic peptide (BNP) below 35 ng/mL, excludes the presence of HF in symptomatic individuals. In individuals with acute dyspnea in the emergency room, however, BNP values over 250 ng/mL or pro-BNP over 1,800 ng/mL indicate HF as the cause of the symptoms. Elderly patients have higher natriuretic peptide levels, as well as comorbidities which may increase these values, such as renal insufficiency.<xref ref-type="bibr" rid="B176"><sup>176</sup></xref> Normal EKG results may be useful in making the hypothesis of HF less likely, while findings of AF, complete left bundle branch block, inactive areas, and LVH, increase the probability of this disease.<xref ref-type="bibr" rid="B176"><sup>176</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B177"><sup>177</sup></xref> Alterations in cardiac geometry and structure occur with aging, including decreases from the base to the apex, right deviation, aortic annulus dilation, and increased interventricular septum thickness, which leads to so-called Sigmoid septum and may cause outflow obstruction.<xref ref-type="bibr" rid="B176"><sup>176</sup></xref> Even though patients with HF with reduced ejection fraction (HFrEF) (LVEF &lt; 40%) and HF with preserved ejection fraction (HFpEF) (LVEF &gt; 50%) are well defined, there is some uncertainty in elderly patients with moderate HF (LVEF 41% to 49%). A recent study demonstrated that this intermediate profile is a distinct entity and it should be categorized as HFrEF due to the elevated prevalence of coronary disease and to the similar benefits of using the standard of treatment indicated for this biomarker.<xref ref-type="bibr" rid="B178"><sup>178</sup></xref> Echocardiography study allows for evaluation of indexed left atrial (LA) volume, the presence of LV hypertrophy, analysis of filling pressures (E/A ratio, E/E&#8217; ratio, and pulmonary flow), diastolic function, inferior vena cava variation, pulmonary BP evaluation, degree of mitral regurgitation, and the presence or absence of aortic stenosis (AS) (especially the low-flow, low-gradient phenotype with normal ejection fraction). It also allows for investigation of etiology, where senile amyloidosis is currently a growing condition in individuals over the age of 70.<xref ref-type="bibr" rid="B176"><sup>176</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B177"><sup>177</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B179"><sup>179</sup></xref> In clinical practice, evaluation of functional state using ergospirometry aids prognostic evaluation and cardiac rehabilitation planning. The presence of fibrosis, cardiac hypertrophy, cardiac chamber dilation, intracardiac thrombus, pericardial thickening, in addition to the study of right ventricle (RV) function, may be evaluated by cardiac resonance. This has become an integral part of the evaluation of myocardial disease patients, as it identifies the cause (inflammation [myocarditis], amyloidosis, sarcoidosis, Chagas disease), cardiomyopathies, and ischemic disease.<xref ref-type="bibr" rid="B176"><sup>176</sup></xref> Myocardial scintigraphy is a useful method in individuals with suspected ischemic heart disease with systolic dysfunction; it is requested to investigate ischemia and/or myocardial viability. Technetium pyrophosphate bone scintigraphy may be useful in diagnosing transthyretin cardiac amyloidosis in elderly hypertrophy and HF patients.<xref ref-type="bibr" rid="B176"><sup>176</sup></xref></p>
          <fig id="f3">
            <label>Figure 1</label>
            <caption>
              <title>Diagnostic flowchart. HF: heart failure; HFpEF: heart failure with preserved ejection fraction; HFrEF: heart failure with reduced ejection fraction.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-112-05-0649-90086-gf01-en.tif"/></fig>
          <table-wrap id="t66">
            <table frame="hsides" rules="groups">
              <colgroup width="25%">
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top">Intervention</th>
                  <th align="center" valign="top">Recommendation</th>
                  <th align="center" valign="top">Grade of recommendation</th>
                  <th align="center" valign="top">Level of evidence</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Oxygen</td>
                  <td align="center" valign="top">In patients with arterial saturation below 90%, respiratory failure, or a high risk of hypoxemia, it is necessary to maintain during the first 6 h or until hemodynamic stabilization is reached</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Nitrates</td>
                  <td align="center" valign="top">In sublingual form, it is recommended for patients with ischemic type chest pain. It may be used in intravenous form in elderly patients with persistent pain and conditions associated with hypertension and heart failure. It should be avoided in cases of hypotension, right ventricular infarction, and severe aortic stenosis</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Morphine</td>
                  <td align="center" valign="top">This should be reserved for patients with unacceptable pain levels. The initial dose is 2 to 4 mg, with 2 to 8 mg increments repeated in 5 to 15 minute intervals</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Beta-blockers</td>
                  <td align="center" valign="top">Great benefits in comparison with younger groups, regarding prevention of ACS and death. Intravenous administration should only be used in specific cases</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">ACEI</td>
                  <td align="center" valign="top">Benefits especially in CHF or LV dysfunction</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top" rowspan="2">Statins</td>
                  <td align="center" valign="top">Dyslipidemia treatment in elderly patients up to age 75 should follow the same orientations as in non-elderly patients</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="center" valign="top">After age 75, doses of lipid-lowering agents should be individualized according to the presence of comorbidities, life expectancy, and polypharmacy</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">ASA</td>
                  <td align="center" valign="top">Indicated for all elderly patients, if there are no contraindications. Benefits are greater in elderly patients</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Clopidogrel</td>
                  <td align="center" valign="top">Indicated for elderly ACS patients with high risks, especially those who will undergo angioplasty. Loading doses are not recommended in elderly patients who are eligible for thrombolytic therapy</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Ticagrelor</td>
                  <td align="center" valign="top">Better evolution than clopidogrel, comparing groups over and under age 75, with no differences in bleeding in either of the 2 groups</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Prasugrel</td>
                  <td align="center" valign="top">Contraindicated in patients &#8805; 75 years old, weight &lt; 60 kg, and stroke/TIA history</td>
                  <td align="center" valign="top">III</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Antithrombins</td>
                  <td align="center" valign="top">Should be administered with caution in ACS patients. Enoxaparin may be administered at reduced doses in patients &gt; 75 years old (0.75 mg/kg, SC, 12/12h)</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top" rowspan="2">Glycoprotein inhibitor IIb/IIIa</td>
                  <td align="center" valign="top">Indicated in the most elderly subgroups at the moment of intervention, excluding renal insufficiency:</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="center" valign="top">ACS-NSTE &#8211; Early intervention strategies, when thienopyridine is not administered</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Thrombolysis</td>
                  <td align="center" valign="top">When indicated, evaluate with attention to contraindications, as they are more frequent in elderly patients. In the event of tenecteplase use in elderly patients &gt; age 75, administer a half-dose</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Primary angioplasty</td>
                  <td align="center" valign="top">Better risk-benefit compared to thrombolytic drugs</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top" rowspan="2">Early catheterization</td>
                  <td align="center" valign="top">Improved short- and long-term evolution. Evidence from randomized, controlled studies are limited in elderly patients and should take risk of bleeding into account. Data are lacking in the &#8805; age 80 subgroup</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="center" valign="top">ACS-STE &#8211; Elderly patients should be considered for early invasive strategies, with the possible option of revascularization</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Cardiac rehabilitation</td>
                  <td align="center" valign="top">The same benefits as in younger groups regarding death prevention</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN31a">
                <p><italic>ACEI: angiotensin converting enzyme inhibitors; ACS: acute coronary syndrome; ACS-NSTE: acute coronary syndrome without ST-segment elevation; ACS-STE: acute coronary syndrome with ST-segment elevation; ASA: acetylsalicylic acid; CHF: congestive heart failure; LV: left ventricle; TIA: transient ischemic accident</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>4.2. Peculiarities of Heart Failure Treatment in Elderly Patients</title>
          <p>HF is prevalent among the elderly, affecting up to 20% of patients &gt; 75 years old.<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> It is characterized by the presentation of systolic dysfunction (HFrEF) or diastolic dysfunction (HFpEF) and high mortality (2-fold risk of all-cause mortality adjusting for age and sex and 4-fold risk of cardiovascular death).<xref ref-type="bibr" rid="B180"><sup>180</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B181"><sup>181</sup></xref> Over the past decades, HFpEF has become the main clinical phenotype.<xref ref-type="bibr" rid="B2"><sup>2</sup></xref></p>
          <p>Polypharmacy is extremely common in this context, with a strong impact on drug interactions, higher rates of adverse effects and poor adherence; however, multidisciplinary and adherence programs have been shown to be useful in this group of patients.<xref ref-type="bibr" rid="B182"><sup>182</sup></xref> Exercise training, in comparison with habitual care, in elderly HFrEF patients in New York Heart Association (NYHA) classes II and III, was shown to be safe, without an increase in mortality and hospitalization and with improvements in the walking test.<xref ref-type="bibr" rid="B183"><sup>183</sup></xref></p>
          <p>The objectives of pharmacological treatment of HF are: reducing mortality and hospitalization; improving functional capacity and quality of life; and including the use of ACEI, ARB, beta-blockers, and aldosterone antagonists. Elderly individuals have frequently been excluded or under-represented in studies performed on HF patients.<xref ref-type="bibr" rid="B184"><sup>184</sup></xref></p>
          <p>Several influential clinical trials have demonstrated the efficacy of ACEI in younger patients (average age of 60/66); however, subgroup analysis of the Heart Outcomes Prevention Evaluation (HOPE) study demonstrated a higher risk reduction in patients &gt; 65 years old, in comparison with the younger group.<xref ref-type="bibr" rid="B184"><sup>184</sup></xref></p>
          <p>ARB have been little evaluated in elderly patients; however, subanalysis of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM-Alternative) study, with 23.3% of its study population &#8805; age 75, demonstrated benefits similar to those reported for the general group.<xref ref-type="bibr" rid="B185"><sup>185</sup></xref></p>
          <p>Regarding beta-blockers, a recent meta-analysis of 12,719 patients did not find any differences in benefits between those defined as &#8220;elderly&#8221; in the clinical trials included and their younger counterparts. It is important to underline the fact that the oldest patient from the individual clinical trials analyzed was 71 years old.<xref ref-type="bibr" rid="B5"><sup>5</sup></xref> The Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure (SENIORS) demonstrated the efficacy of nebivolol in CHF patients &gt; 70 years old. Subanalysis of the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) study provided evidence that beta-blockers may be associated with beneficial effects in patients &#8805; 75 years old.<xref ref-type="bibr" rid="B186"><sup>186</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B187"><sup>187</sup></xref></p>
          <p>The Euro Heart Failure Survey II has suggested that the use of ACEI and/or beta-blockers is associated with a significant decrease in short-term mortality in octogenarians. The Euro HF Survey II, on the other hand, did not show improvements in mortality during 1 year with the use of beta-blockers; this is possibly related to the higher number of elderly HFpEF patients in this study.<xref ref-type="bibr" rid="B188"><sup>188</sup></xref></p>
          <p>In the most important studies with aldosterone antagonists, the Randomized Aldactone Evaluation Study (RALES) and the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), the average patient age was 67 and 64, respectively. Their use, in elderly patients, however, should be carefully monitored in accordance with renal dysfunction and the underlying drug interaction. In the Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM) study, symptomatic hypotension in patients &gt; age 75 was more frequent in the sacubitril/valsartan group (18%) than in the enalapril group (12%).<xref ref-type="bibr" rid="B189"><sup>189</sup></xref></p>
          <p>In summary, current orientations recommend a therapeutic approach similar to the one applied to younger patients for HF treatment, with caution regarding interactions and tolerance.<xref ref-type="bibr" rid="B176"><sup>176</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B190"><sup>190</sup></xref></p>
        </sec>
        <sec>
          <title>4.3. General Recommendations for Elderly Heart Failure Patients</title>
          <table-wrap id="t67">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top">Complementary diagnostic methods of CHF in elderly patients</th>
                  <th align="center" valign="top">Grade of recommendation</th>
                  <th align="center" valign="top">Level of evidence</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Transthoracic echocardiogram recommended for evaluating structure and function in HF and establishing diagnosis of HFrEF and/or HFpEF</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Transthoracic echocardiogram recommended for evaluating resynchronization/ICD candidates</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Repeat evaluation of ventricular function and measures of structural remodeling in patients with CHF, change in clinical status, or decompensation</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">MR with delayed enhancement should be considered in patients with dilated cardiomyopathy to differentiate between ischemic and non-ischemic etiology</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">MR recommended for cardiac tissue characterization when myocarditis, amyloidosis, sarcoidosis, or non-compacted myocardium are suspected</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Non-invasive stress exams (resonance, echocardiogram, SPECT, PET) are recommended for evaluating myocardial ischemia and viability in patients with CAD and CHF before deciding on revascularization</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Cinecoronariography recommended in patients with CHF and angina for diagnosis of CAD</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Coronary angiotomography in patients with CHF and pre-test likelihood indicating low or intermediate risk and in patients whose non-invasive stress exams suggest CAD, with the objective of excluding invasive exams</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Hemogram, sodium, potassium, urea, creatinine (clearance), hepatic function, glucose, glycated hemoglobin, TSH, ferritin</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Natriuretic peptides</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Electrocardiogram recommended for evaluating rhythm, heart rate, morphology and QRS duration</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Chest radiography recommended to exclude pulmonary alterations. In cases of acute decompensation to detect edema/pulmonary congestion</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">C</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Endomyocardial biopsy should be considered for diagnosing specific causes in cases of rapid and progressive worsening in spite of standard therapy</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN32a">
                <p><italic>CAD: coronary artery disease; CHF: congestive heart failure; HF: heart failure; HFpEF: heart failure with preserved ejection fraction; HFrEF: heart failure with reduced ejection fraction; ICD: implantable cardioverter-defibrillator; MR: magnetic resonance; PET: positron emission tomography; SPECT: single photon emission computed tomography; TSH: thyroid-stimulating hormone</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <table-wrap id="t68">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top" colspan="3">Treatment of comorbidities</th>
                </tr>
                <tr>
                  <th align="left" valign="middle">Recommendation</th>
                  <th align="center" valign="top">Grade of recommendation</th>
                  <th align="center" valign="top">Level of evidence</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Iron deficiency &#8211; IV iron replacement in patients with ferritin &lt; 100 ng/ml or ferritin between 100 and 199 ng/ml and transferrin saturation &lt; 20% with the objective of improving symptoms and quality of life</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Diabetes &#8211; metformin use</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">C</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN33a">
                <p><italic>IV: intravenous</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <table-wrap id="t69">
            <table frame="hsides" rules="groups">
              <colgroup width="33%">
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top" colspan="3">Grade of recommendation for pharmacological treatment of HFrEF FC II to IV</th>
                </tr>
                <tr>
                  <th align="left" valign="middle">Recommendation</th>
                  <th align="center" valign="top">Classification of recommendation</th>
                  <th align="center" valign="top">Level of evidence</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">ACEI in conjunction with beta-blockers with the objective of reducing mortality and hospitalization</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top">ARB in conjunction with beta-blockers with the objective of reducing hospitalization and mortality in patients with ACEI intolerance</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Addition of aldosterone blockers in symptomatic patients, with LVEF &#8804; 35%, associated with ACEI (or ARB) and beta-blockers</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">A</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Diuretics to improve symptoms in patients with congestion</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Angiotensin receptor-neprilysin inhibitor (sacubitril/valsartan), to substitute ACEI in order to reduce mortality and hospitalization in patients who continue to be symptomatic in spite of treatment with ACEI (or ARB) and beta-blockers</td>
                  <td align="center" valign="top">I</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Hydralazine and isosorbide dinitrate in African-American patients with EF &lt; 35% or EF &lt; 45% with ventricular dilatation who continue to be symptomatic, with FC III-IV, in spite of treatment with ACEI (or ARB) and beta-blockers to reduce mortality and hospitalization</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Hydralazine and isosorbide dinitrate in symptomatic patients with HFrEF who do not tolerate ACEI or ARB to reduce mortality</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Digoxin in symptomatic patients with sinus rhythm in spite of treatment with ACEI (or ARB) and beta-blockers to reduce hospitalization</td>
                  <td align="center" valign="top">IIb</td>
                  <td align="center" valign="top">B</td>
                </tr>
                <tr>
                  <td align="left" valign="top">An If channel inhibitor (ivabradine) may be used in symptomatic patients with sinus rhythm, EF &lt; 35%, and HR &gt; 70 bpm, in spite of treatment with ACEI (or ARB) and beta-blockers to reduce hospitalization and mortality</td>
                  <td align="center" valign="top">IIa</td>
                  <td align="center" valign="top">B</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN34a">
                <p><italic>ACEI: angiotensin converting enzyme inhibitors; ARB: angiotensin receptor blockers; EF: ejection fraction; FC: New York Heart Association functional class; HFrEF: heart failure with reduced ejection fraction; HR: heart rate; LVEF: left ventricular ejection fraction</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <table-wrap id="t70">
            <table frame="hsides" rules="groups">
              <colgroup width="20%">
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr>
                  <th align="left" valign="top" colspan="5">Available drugs, initial and target doses, dose adjustments, and safety in elderly patients</th>
                </tr>
                <tr>
                  <th align="left" valign="top">Drugs</th>
                  <th align="center" valign="top">Initial dose</th>
                  <th align="center" valign="top">Maximum dose</th>
                  <th align="center" valign="top">Dose adjustment for elderly patients</th>
                  <th align="center" valign="top">Safety in elderly patients</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="top">Captopril</td>
                  <td align="center" valign="top">6.25 mg 3&#215;/day</td>
                  <td align="center" valign="top">50 mg 3&#215;/day</td>
                  <td align="center" valign="top">None</td>
                  <td align="center" valign="top">Increase in orthostatic hypotension Take before bedtime Decrease diuretics</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Enalapril</td>
                  <td align="center" valign="top">2.5 mg 2&#215;/day</td>
                  <td align="center" valign="top">10&#8211;20 mg 2&#215;/day</td>
                  <td align="center" valign="top">None</td>
                  <td align="center" valign="top">More susceptible to renal dysfunction</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Lisinopril</td>
                  <td align="center" valign="top">2.5&#8211;5.0 mg 1&#215;/day</td>
                  <td align="center" valign="top">20&#8211;40 mg 1&#215;/day</td>
                  <td align="center" valign="top">None</td>
                  <td align="center" valign="top">Avoid use of NHAI drugs</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Perindopril</td>
                  <td align="center" valign="top">2.0 mg 1&#215;/day</td>
                  <td align="center" valign="top">8,0&#8211;16 mg 1&#215;/day</td>
                  <td align="center" valign="top">None</td>
                  <td align="center" valign="top"/>
                </tr>
                <tr>
                  <td align="left" valign="top">Ramipril</td>
                  <td align="center" valign="top">1.25&#8211;2.5 mg 1&#215;/day</td>
                  <td align="center" valign="top">10 mg 1&#215;/day</td>
                  <td align="center" valign="top">Adjust according to renal function</td>
                  <td align="center" valign="top"/>
                </tr>
                <tr>
                  <td align="left" valign="top">Candesartan</td>
                  <td align="center" valign="top">4.0&#8211;8.0 mg 1&#215;/day</td>
                  <td align="center" valign="top">32 mg</td>
                  <td align="center" valign="top">None, but elevated AUC and Cmax</td>
                  <td align="center" valign="top">Similar to that of ACEI</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Losartan</td>
                  <td align="center" valign="top">25 mg 1&#215;/day</td>
                  <td align="center" valign="top">50&#8211;100 mg</td>
                  <td align="center" valign="top">None</td>
                  <td align="center" valign="top"/>
                </tr>
                <tr>
                  <td align="left" valign="top">Valsartan</td>
                  <td align="center" valign="top">40 mg 2&#215;/day</td>
                  <td align="center" valign="top">320 mg</td>
                  <td align="center" valign="top">None</td>
                  <td align="center" valign="top"/>
                </tr>
                <tr>
                  <td align="left" valign="top" rowspan="9">Bisoprolol</td>
                  <td align="center" valign="top" rowspan="9">1.25 mg 1&#215;/day</td>
                  <td align="center" valign="top" rowspan="9">10 mg 1&#215;/day</td>
                  <td align="center" valign="top" rowspan="9"/>
                  <td align="center" valign="top">Water retention:</td>
                </tr>
                <tr>
                  <td align="center" valign="top">- Monitor weight daily</td>
                </tr>
                <tr>
                  <td align="center" valign="top">- Adjust diuretic dosage</td>
                </tr>
                <tr>
                  <td align="center" valign="top">Risk of hypotension and bradycardia:</td>
                </tr>
                <tr>
                  <td align="center" valign="top">- Start with a low dose and increase progressively</td>
                </tr>
                <tr>
                  <td align="center" valign="top">- Adequate hydration</td>
                </tr>
                <tr>
                  <td align="center" valign="top">Increased fatigue:</td>
                </tr>
                <tr>
                  <td align="center" valign="top">- Improves over time</td>
                </tr>
                <tr>
                  <td align="center" valign="top">- Consider comorbidities anemia</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Carvedilol</td>
                  <td align="center" valign="top">3.12 5mg 2&#215;/day</td>
                  <td align="center" valign="top">50 mg/day</td>
                  <td align="center" valign="top">None</td>
                  <td align="center" valign="top"/>
                </tr>
                <tr>
                  <td align="left" valign="top">Metoprolol succinate</td>
                  <td align="center" valign="top">12.5&#8211;25 mg</td>
                  <td align="center" valign="top">200 mg/day</td>
                  <td align="center" valign="top">None</td>
                  <td align="center" valign="top"/>
                </tr>
                <tr>
                  <td align="left" valign="top">Nebivolol</td>
                  <td align="center" valign="top">1.25 mg</td>
                  <td align="center" valign="top">10 mg</td>
                  <td align="center" valign="top">None</td>
                  <td align="center" valign="top"/>
                </tr>
                <tr>
                  <td align="left" valign="top">Spironolactone</td>
                  <td align="center" valign="top">12.5&#8211;25 mg</td>
                  <td align="center" valign="top">25&#8211;50 mg</td>
                  <td align="center" valign="top">None</td>
                  <td align="center" valign="top">Increased risk of hyperkalemia and renal dysfunction Monitor K and creatinine</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Furosemide</td>
                  <td align="center" valign="top">20&#8211;40 mg/day 1 or 2&#215;/day</td>
                  <td align="center" valign="top">600 mg (usual 40&#8211;240 mg/day)</td>
                  <td align="center" valign="top">Start 20 mg/day</td>
                  <td align="center" valign="top">Frequent monitoring Increased risk of alterations in water balance and electrolyte disturbances</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Bumetanide</td>
                  <td align="center" valign="top">0.5&#8211;1 mg 1 or 2&#215;/day</td>
                  <td align="center" valign="top">10 mg Usual (1&#8211;5 mg/day)</td>
                  <td align="center" valign="top">None</td>
                  <td align="center" valign="top">Frequent monitoring Increased risk of alterations in water balance and electrolyte disturbances</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Hydrochlorothiazide</td>
                  <td align="center" valign="top">25 mg</td>
                  <td align="center" valign="top">200 mg/day Usual (12.5&#8211;100 mg/day)</td>
                  <td align="center" valign="top">Start 12.5 mg&#8211;25 mg</td>
                  <td align="center" valign="top">Monitor fluid volume and electrolyte status</td>
                </tr>
                <tr>
                  <td align="left" valign="top">Chlorthalidone</td>
                  <td align="center" valign="top">12.5&#8211;25 mg</td>
                  <td align="center" valign="top">100 mg</td>
                  <td align="center" valign="top">None</td>
                  <td align="center" valign="top">Monitor fluid volume and electrolyte status</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN35a">
                <p><italic>ACEI: angiotensin converting enzyme inhibitors; AUC: area under curve; NHAI: non-hormonal anti-inflammatory</italic>.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
      </sec>
      <sec>
        <title>5. Arterial Hypertension in The Elderly</title>
        <sec>
          <title>5.1. Diagnostic Peculiarities</title>
          <p>A Brazilian epidemiological study titled the Multicenter Study of Elderly Patients in Outpatient Clinics of Cardiology and Geriatric Brazilian Institutions (EMI, acronym in Portuguese)<xref ref-type="bibr" rid="B191"><sup>191</sup></xref> demonstrated that SAH is the main risk factor among elderly Brazilians. It is found in 65% of elderly outpatients and 80% of women &gt; 75 years old. Aging produces vascular alterations, such as arterial stiffening, reduced elasticity and vascular compliance, reduced vasodilation capacity, increased SBP, decreased sensitivity to volume changes, slowed ventricular relaxation, increased cardiac workload, loss of myocytes, and compensatory hypertrophy.<xref ref-type="bibr" rid="B192"><sup>192</sup></xref> These alterations lead to peculiarities in diagnosing and treating SAH in elderly patients.</p>
          <sec>
            <title>5.1.1. Peculiarities in Measuring Blood Pressure</title>
            <p>In elderly patients, BP has high variability. It is necessary to take special care in measuring BP, owing to the possible presence of the following factors:</p>
            <list list-type="alpha-lower">
              <list-item>
                <p>OH: defined as a drop in SBP of &gt; 20 mmHg or in diastolic blood pressure (DBP) of &gt; 10 mmHg, following 3 minutes in the orthostatic position. BP should be checked in the sitting, lying, and standing positions, given that atherosclerotic alterations in the carotid sinus regions may reduce baroreceptor sensitivity, leading to reduced postural reflexes and, thus, predisposing the patient to OH.<xref ref-type="bibr" rid="B3"><sup>3</sup></xref> Furthermore, comorbidities, such as peripheral polyneuropathy and Parkinson&#8217;s disease, as well as the use of diuretic, antidepressant, vasodilator, and beta-blocker drugs may also lead to OH in up to 34% of elderly patients &gt; age 75.</p>
              </list-item>
              <list-item>
                <p>Auscultatory gap: a sitution in which, after auscultation of the first Korotkoff sound, the sound disappears completely and only reappears after the decrease in SBP, but before the beginning of the last phase of Korotkoff sounds. This leads to errors in diagnosing SBP at lower levels and false diagnoses of normotension. In order to avoid this measurement error, it is necessary to estimate systolic pressure using the radial pulse palpatory method, raising cuff pressure 20 to 30 mmHg above this point.<xref ref-type="bibr" rid="B193"><sup>193</sup></xref></p>
              </list-item>
              <list-item>
                <p>Pseudo-hypertension: pseudo-hypertension may appear in elderly patients with pronounced atherosclerosis, arterial wall calcification, and vessel stiffening. In this situation, it is sufficient to inflate the cuff in order to collapse the brachial artery.<xref ref-type="bibr" rid="B193"><sup>193</sup></xref> Osler&#8217;s maneuver is used to identify this. The maneuver consists of inflating the cuff above systolic pressure levels and, concomitantly, palpating the radial artery. If it continues to be palpable, this suggests that the artery is stiff and indicates that the index obtained by auscultation does not express the true SBP. Pseudo-arterial hypertension may also be suspected when SBP is elevated in patients who do not present injuries in target organs or in those who manifest hypotension following treatment with low doses of anti-hypertensive drugs.</p>
              </list-item>
              <list-item>
                <p>Arterial hypertension during exercise: although BP is habitually higher during physical exercise, this increase is greater in elderly adults, due to arterial stiffness. Values for diagnosing SAH during exercise are not clear. Physically deconditioned patients respond with greater increases in BP than conditioned patients.</p>
              </list-item>
              <list-item>
                <p>White coat hypertension: this occurs when BP increases during a clinical visit but remains normal during daily activity. This can be better evaluated by 24-hour ambulatory blood pressure monitoring (ABPM) or home blood pressure monitoring (HBPM).<xref ref-type="bibr" rid="B193"><sup>193</sup></xref> Serial measurements may minimize this condition.</p>
              </list-item>
              <list-item>
                <p>Masked arterial hypertension: this is the opposite of white coat hypertension, namely, pressure is high during daily activities and normal during the clinical visit.<xref ref-type="bibr" rid="B193"><sup>193</sup></xref> This may also be evaluated by 24-h ABPM or HBPM.</p>
              </list-item>
              <list-item>
                <p>Isolated systolic hypertension (ISH) and pulse pressure (PP): ISH and PP are cardiovascular risk factors in elderly patients.<xref ref-type="bibr" rid="B191"><sup>191</sup></xref> ISH is due to lower distensibility and elasticity in the large capacitance vessels, such as the aorta, which results in increased pulse wave velocity (PWV). This increase in PWV is accompanied by an increase in reflex wave velocity, which returns from peripheral to central circulation.<xref ref-type="bibr" rid="B191"><sup>191</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B192"><sup>192</sup></xref> In elderly patients, the reflex wave reaches the ascending aorta during systole, leading to an even higher increase in SBP. Loss of reflex wave in protodiastole makes diastolic pressure remain equal or decrease.<xref ref-type="bibr" rid="B192"><sup>192</sup></xref> The final effect consists of a predominant increase in SBP, with DBP remaining normal or even low. Characteristics of ISH include SBP &#8805; 140 mmHg and DBP &lt; 90 mmHg.<xref ref-type="bibr" rid="B193"><sup>193</sup></xref> PP is defined as the difference between SBP and DBP. This occurs due to the progressive loss of arterial elasticity, with a consequent decrease in vascular complacency. DBP tends to remain normal or even low. Limits for abnormal PP values have yet to be defined.<xref ref-type="bibr" rid="B191"><sup>191</sup></xref> The Framingham study demonstrated a higher cardiovascular risk associated with higher PP, in patients between the ages of 50 and 79, as well as an important role of low DBP in this association.<xref ref-type="bibr" rid="B3"><sup>3</sup></xref> In addition to the factors mentioned, target organ injuries should be investigated (eye fundus changes, LV hypertrophy, and peripheral and renal atherosclerosis), and the possibility of secondary SAH should be evaluated. The following are suspicious factors:<xref ref-type="bibr" rid="B193"><sup>193</sup></xref></p>
                <list list-type="alpha-lower">
                  <list-item>
                    <p>Sudden onset of SAH or acute worsening</p>
                  </list-item>
                  <list-item>
                    <p>Abdominal murmur</p>
                  </list-item>
                  <list-item>
                    <p>SAH resistant to 3 or more drugs</p>
                  </list-item>
                  <list-item>
                    <p>Creatinine increase over 30% with the use of ACEI or ARB</p>
                  </list-item>
                  <list-item>
                    <p>Systemic atherosclerotic disease in smokers and patients with dyslipidemia</p>
                  </list-item>
                  <list-item>
                    <p>Recurrent hypertensive pulmonary edema</p>
                  </list-item>
                  <list-item>
                    <p>Pheochromocytoma and hyperaldosteronism should be adequately investigated with more specific exams, because, even though they are less frequent in elderly patients, once they are diagnosed and treated, they may result in the patient being cured.</p>
                  </list-item>
                </list>
              </list-item>
            </list>
            <p>Among secondary causes of SAH, the following stand out: aortic regurgitation (AR), hyperthyroidism, renovascular atherosclerosis, and use of drugs that increase pressure, such as non-hormonal anti-inflammatory agents, antihistamines, decongestants, corticosteroides, MAOI, and TCA.	</p>
          </sec>
          <sec>
            <title>5.1.2. Peculiarities of Clinical Laboratory Investigation</title>
            <p>The objective of clinical laboratory investigation is to confirm that BP is increased; identify causes of SAH, target organ injuries, and associated diseases; and stratify cardiovascular risk. In addition to clinical history, cognitive tests, and physical examination including BMI and abdominal circumference, the following should be performed:</p>
            <list list-type="alpha-lower">
              <list-item>
                <p>Resting EKG.</p>
              </list-item>
              <list-item>
                <p>Urine examination (biochemical and sediment)</p>
              </list-item>
              <list-item>
                <p>Blood tests: complete blood count, creatinine, blood glucose, potassium, fasting blood glucose, glycohemoglobin, total cholesterol and fractions, triglycerides, and uric acid. Blood levels of creatinine may be normal, in spite of declined renal function. This fact results from the progressive loss of muscle mass, a determining factor of creatinine production. Thus, creatinine levels &gt; 1.5 mg/dL are considered abnormal in elderly patients. The formula most used to calculate estimated glomerular filtration rate (eGFR) is the Cockroff-Gault (mL/min): (140 &#8211; age) &#215; weight (kg)/plasma creatinine (mg/dL) &#215; 72<italic>,</italic>with a coefficient of 0.85 for women. Interpretation: normal renal function, &gt; 90 mL/min; slight renal dysfunction, 60 to 90 mL/min; moderate renal dysfunction, 30 to 60 mL/min; severe renal dysfunction, &lt; 30 mL/min.</p>
              </list-item>
              <list-item>
                <p>ABPM and HBPM: to investigate white coat SAH and masked SAH, in cases where it is necessary to investigate episodes of arterial hypotension, or to evaluate the efficacy of SAH therapy.<xref ref-type="bibr" rid="B193"><sup>193</sup></xref></p>
              </list-item>
            </list>
          </sec>
        </sec>
        <sec>
          <title>5.2. Treatment Peculiarities</title>
          <sec>
            <title>5.2.1. Therapeutic Goals for Elderly Patients</title>
            <p>Treating SAH in elderly patients represents a great challenge, as it involves a heterogeneous group, with multiple comorbidities, cognitive problems, risk of falling, polypharmacy, and frailty syndrome. Therapeutic goals for elderly patients should thus be individualized based on multidisciplinary team judgment, and they should consider patient preferences.<xref ref-type="bibr" rid="B193"><sup>193</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B194"><sup>194</sup></xref> Dose adjustments should occur every 4 weeks, in order to avoid abrupt reductions of BP. The Hypertension in the Very Elderly Trial (HYVET) randomized, placebo-controlled study<xref ref-type="bibr" rid="B194"><sup>194</sup></xref> included 3,845 patients with SBP &#8805; 160 mmHg over the age of 80, with an average age of 83.6. Target blood pressure was 150/80 mmHg. They demonstrated that treatment with indapamide, with or without perindopril, was beneficial in octogenarians. In the intention-to-treat analysis, there was a 30% reduction in rate of fatal or non-fatal stroke, 39% reduction in the rate of death from stroke, a 21% reduction in death from any cause, a 23% reduction of in the rate of death from cardiovascular causes, and a 64% reduction in the rate of HF. Fewer severe adverse events occurred in the active treatment group (358 versus 448 in the placebo group). There is evidence that greatly lowering BP in elderly patients may be harmful; this fact is known as the J- or U-curve.<xref ref-type="bibr" rid="B191"><sup>191</sup></xref> The recent SPRINT study<xref ref-type="bibr" rid="B149"><sup>149</sup></xref> sought to evaluate two different BP goals. In the standard group, the goal was SBP &lt; 140 mmHg and, in the intensive treatment group, the goal was SBP &lt; 120 mmHg. The intensive treatment group had a significant reduction in primary events (infarction, other acute coronary syndromes, stroke, HF, or death from cardiovascular causes) in comparison with the standard treatment group. Although the initial impression may be that more intensive goals may be more beneficial, it is necessary to consider that there was an increase in the number of severe adverse events, such as hypotension, syncope, electrolytic disorders, and acute renal insufficiency, in the intensive treatment group. Another important study was the ACCORD,<xref ref-type="bibr" rid="B35"><sup>35</sup></xref> performed with 10,251 diabetic patients, ages 40 to 79, 4,733 of which were also randomized for BP reduction &lt; 140 mmHg or &lt; 120 mmHg. However, BP reduction with more intensive goals did not succeed in significantly reducing the risk of the study&#8217;s primary outcome (death from CVD, nonfatal infarction, and nonfatal stroke). Thus, to date, the III Geriatric Cardiology Guidelines recommends SBP levels &#8804; 130 mmHg for elderly patients &#8805; age 65, who are considered robust and who do not have frailty criteria.<xref ref-type="bibr" rid="B195"><sup>195</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B196"><sup>196</sup></xref> For patients &#8804; 80 years old, without frailty, SBP levels &lt; 140 mmHg may be considered;<xref ref-type="bibr" rid="B195"><sup>195</sup></xref> in patients &#8805; age 80 with SBP &#8805; 160 mmHg, an initial reduction to SBP between 150 and 140 mmHg may be considered;<xref ref-type="bibr" rid="B7"><sup>7</sup></xref> in fragile elderly patients or patients with multiple comorbidities, the therapeutic goal should be individualized, considering each case&#8217;s risk-benefit ratios.<xref ref-type="bibr" rid="B196"><sup>196</sup></xref></p>
          </sec>
          <sec>
            <title>5.2.2. Medical and Non-Medical Treatments</title>
            <p>Salt reduction should be cautious and well accompanied by the doctor, given that the elderly patient&#8217;s diminished taste sensitivity may make food appear blander, causing the patient to eat less and thus bringing about the risk of malnutrition. It is also necessary to remember that elderly patients rarely present only one chronic disease. The evaluation of multimorbidities generally defines what the best treatment is and what drugs should be avoided in each specific case. Treatment should be initiated with low doses, and dose adjustments should be gradual. Adherence needs to be stimulated, if possible, by monthly control at the beginning of treatment and at each dose adjustment. The most commonly used drugs in elderly patients are:</p>
            <list list-type="alpha-lower">
              <list-item>
                <p>Diuretics: thiazides and correlates (hydrochlorothiazide, chlorthalidone, indapamide) are considered first-line drugs in elderly patients without comorbidities. Their use is preferential in osteoporosis patients, as they decrease urinary excretion of calcium, and in initial phases of congestive heart failure (CHF), as they reduce preload, volume, and pulmonary congestion. Recommended doses of hydrochlorothiazide: 6.25 to 25 mg/day, maintaining efficacy and reducing adverse metabolic effects.<xref ref-type="bibr" rid="B191"><sup>191</sup></xref> In most cases, diuretics are associated with therapeutic schedules. However, they should be avoided in elderly patients with incipient urinary incontinence, gout (because they increase uric acid) and prostatism.<xref ref-type="bibr" rid="B191"><sup>191</sup></xref> Attention should be paid to blood glucose in elderly patients with concomitant use of thiazides and oral antidiabetics or insulin, given that thiazides may increase blood glucose and interfere with diabetes control.</p>
              </list-item>
              <list-item>
                <p>Calcium channel blockers: they include both dihydropyridine and non-dihydropyridine derivatives. Dihydropyridine derivatives have major vasodilatory effects. The most recent generation provokes less edema. They are very commonly used in elderly SAH and symptomatic coronary disease patients. Non-dihydropyridine derivatives, especially verapamil, have fewer vasodilatory effects, and they are not usually prescribed to elderly patients, as they may alter electrical impulses of atrioventricular conduction. Verapamil may, furthermore, provoke intestinal constipation.</p>
              </list-item>
              <list-item>
                <p>ACEI: they continue to be efficacious in elderly patients, notwithstanding the decrease in renin with aging. They decrease cardiovascular events and should be used in elderly patients with SAH and HF or asymptomatic ventricular dysfunction. Adverse effects include changes in taste, especially with captopril, which may reduce food intake, and dry cough, which limit their use. It is fundamental to check potassium, due to frequent reductions in renal function.</p>
              </list-item>
              <list-item>
                <p>Angiotensin II receptor antagonists (ARA-II): they are effective in HF, and they have an established renal and cardiac protective action in type 2 diabetes with nefropathy.<xref ref-type="bibr" rid="B191"><sup>191</sup></xref> ARA-II have a favorable tolerability profile, with few adverse effects (occasional dizziness and, rarely, hypersensitive skin reaction). They are well used in cases of ACEI intolerance.<xref ref-type="bibr" rid="B193"><sup>193</sup></xref></p>
              </list-item>
              <list-item>
                <p>Beta-blockers: they are not used as initial monotherapy in elderly patients without comorbidities, due to their lower effects on BP reduction; however, in association with diuretics, they present good results. They are mainly used in elderly patients with SAH and coronary insufficiency or HF. Less liposoluble beta-blockers, such as atenolol, metoprolol, and bisoprolol, are recommended for elderly patients because they have lower risks of collateral effects on the central nervous system (depression, drowsiness, confusion, sleep disturbances).<xref ref-type="bibr" rid="B193"><sup>193</sup></xref></p>
              </list-item>
            </list>
            <p>In summary, elderly patients have particularities regarding SAH diagnosis and approach. It is necessary to consider each patient&#8217;s comorbidities and particularities, including functional status, which may be determining factors for setting BP goals and for patient decision making.</p>
            <table-wrap id="t71">
              <table frame="hsides" rules="groups">
                <colgroup width="33%">
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <th align="left" valign="middle">Recommendation</th>
                    <th align="center" valign="top">Grade of recommendation</th>
                    <th align="center" valign="top">Level of evidence</th>
                  </tr>
                </thead>
                <tbody style="border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <td align="left" valign="top">SBP &#8804; 130 mmHg for elderly patients &#8805; age 65, without frailty</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">A</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">SBP &lt; 140 mmHg for elderly patients &#8804; age 80, without frailty</td>
                    <td align="center" valign="top">IIb</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">For elderly patients &gt; age 80, with initial SBP &#8805; 160 mmHg, initial SBP reduction between 150 and 140 mmHg</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">In fragile elderly patients or patients with multiple comorbidities, the therapeutic goal should be individualized, considering risk-benefit ratios</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN36a">
                  <p><italic>SBP: systolic blood pressure</italic>.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </sec>
        </sec>
      </sec>
      <sec>
        <title>6. Valvulopathies</title>
        <sec>
          <title>6.1. Mitral Stenosis</title>
          <sec>
            <title>6.1.1. Diagnostic Peculiarities</title>
            <p>Mitral stenosis (MS) is rare in elderly patients (present in 6% of patients with mitral annulus calcification).<xref ref-type="bibr" rid="B197"><sup>197</sup></xref></p>
            <p>Etiology &#8211; Sequel of rheumatic carditis or calcification of the mitral valve apparatus in patients &gt; 85 years old.<xref ref-type="bibr" rid="B198"><sup>198</sup></xref></p>
            <p>Symptoms &#8211; similar to those observed in non-elderly patients. Symptoms may be absent. The most frequent are dyspnea and cough, which may be accompanied by hemoptoic sputum. It may manifest as systemic embolism or AF.</p>
            <p>Physical examination &#8211; Hyperphonetic first heart sound and apical mid-diastolic murmur with thrill may be absent. The opening snap of the mitral valve is rarely auscultated. Most patients &gt; age 80 present AF with elevated HR which, in association with a greater anteroposterior thorax diameter, makes auscultation difficult. The more fibrosis and calcification are present in the mitral valve, the less audible the auscultatory signs of MS will be. Diagnostic suspicion may be established based on signs of pulmonary arterial hypertension (P2 hyperphonesis in the second heart sound, RV insufficiency, pulmonary and tricuspid regurgitation). In elderly pulmonary arterial hypertension patients without any other evident cause, it is important to investigate MS.<xref ref-type="bibr" rid="B199"><sup>199</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B202"><sup>202</sup></xref></p>
            <p>Complementary exams &#8211; EKG, chest radiography, and echocardiogram are sufficient, in most cases, to confirm diagnosis and estimate severity. The following may be found in the EKG: left atrial overload (LAO), RV hypertrophy, and AF. Chest radiography findings include: increased LA, mitral valve calcification, and posterior displacement of the barium-filled esophagus. Echocardiography data include: mitral annulus calcification (in 60% of elderly patients &gt; age 85),<xref ref-type="bibr" rid="B4"><sup>4</sup></xref> mitral valve area (<xref ref-type="table" rid="t72">Table 8</xref>), pulmonary BP, and status of the valvular apparatus (mobility, thickening, and subvalvular impairment).<xref ref-type="bibr" rid="B5"><sup>5</sup></xref></p>
            <table-wrap id="t72">
              <label>Table 8</label>
              <caption>
                <title>Severity of mitral stenosis</title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup width="33%">
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <th align="center" valign="top"/>
                    <th align="center" valign="top">Pressure gradient (LA-LV) in mmHg</th>
                    <th align="center" valign="top">Mitral valve area (cm&#178;)</th>
                  </tr>
                </thead>
                <tbody style="border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <td align="left" valign="top">Mild</td>
                    <td align="center" valign="top">&lt; 5</td>
                    <td align="center" valign="top">&gt; 1.5</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Moderate</td>
                    <td align="center" valign="top">5 a 10</td>
                    <td align="center" valign="top">1 a 1.5</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Severe</td>
                    <td align="center" valign="top">&gt; 10</td>
                    <td align="center" valign="top">&lt; 1</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN19">
                  <p>LA: left atrium. LV: left ventricle.<xref ref-type="bibr" rid="B202"><sup>202</sup></xref></p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </sec>
          <sec>
            <title>6.1.2. Treatment Peculiarities</title>
            <p>Clinical treatment &#8211; Patients with mild MS are generally asymptomatic, and they do not need to receive medication,<xref ref-type="bibr" rid="B203"><sup>203</sup></xref> unless they also suffer from AF. Unlike younger patients, elderly MS patients who develop AF have a higher chance of showing symptoms of HF, owing to the concomitant present of diastolic dysfunction. Thus, in cases of paroxysmal AF with hemodynamic deterioration, even if MS is mild, electrical cardioversion is indicated. Patients with MS and AF, be it permanent, persistent, or paroxysmal, should constantly use warfarin, regardless of risk scores, with the aim of keeping the international normalized ratio (INR) between 2 and 3, unless there is a formal contraindication.<xref ref-type="bibr" rid="B204"><sup>204</sup></xref> Although some publications recommend the use of new oral anticoagulants in this situation, these data have yet to be evaluated in comparative studies.<xref ref-type="bibr" rid="B205"><sup>205</sup></xref> The finding of LA thrombus or the occurrence of a systemic embolic event, even in the presence sinus rhythm (SR), also indicate the need for anticoagulant use. In MS of rheumatic etiology, prophylaxis for rheumatic fever is not necessary, given that elderly patients rarely have relapses of this disease.<xref ref-type="bibr" rid="B206"><sup>206</sup></xref> Early treatment of bacterial infections is recommended with the aim of protecting the patient from the risk of infective endocarditis (IE). Chemoprophylaxis against IE in elderly MS patients is not indicated.<xref ref-type="bibr" rid="B207"><sup>207</sup></xref> In symptomatic patients with moderate to severe MS, loop diuretics are the best option for controlling pulmonary or systemic congestion, and beta-blockers are indicated for reducing HR and facilitating atrial emptying. There is no evidence that the use of beta-blockers is beneficial in patients with SR who do not have elevated HR.<xref ref-type="bibr" rid="B208"><sup>208</sup></xref> In the presence of AF with elevated ventricular response, beta-blockers are the drugs of choice for reducing HR. In cases where they are contraindicated, nondihydropyridine calcium channel blockers or digitalis may be used. In the presence of signs of RV failure with associated hepatomegaly, due to the frequent coexistence of secondary hyperaldosteronism, elevated doses of spironolactone (100 mg/day) are an option.<xref ref-type="bibr" rid="B209"><sup>209</sup></xref> Caution is necessary with the risk of hyperkalemia.</p>
            <p>Options for correcting MS &#8211; When evaluating an elderly patient with MS who has been indicated for intervention, the following should be considered and discussed with the patient and/or family members: etiology, whether rheumatic or degenerative; patient life expectancy; evaluation of functionality; and the presence of multimorbidities. There are 2 options for correcting rheumatic MS: percutaneous balloon mitral valvuloplasty (PBMV) or extracorporeal circulation surgery. Randomized clinical trials have shown that, in selected cases, PBMV offers immediate and long-term results similar to those of open commissurotomy.<xref ref-type="bibr" rid="B210"><sup>210</sup></xref> For this intervention, presence of favorable valve morphology is important. This may be evaluated by several proposed echocardiography criteria, the Wilkins and Block score being the most widely used.<xref ref-type="bibr" rid="B211"><sup>211</sup></xref> It is, additionally, necessary to respect contraindications to this procedure (presence of LA thrombus or mitral regurgitation with more than a mild degree of severity). Unfortunately, elderly patients frequently have valve morphologies which are unfavorable for this procedure, whether the etiology be rheumatic or degenerative.<xref ref-type="bibr" rid="B212"><sup>212</sup></xref> In the latter case, owing to the fact there is no commissural fusion, as occurs in rheumatic disease, the success of PBMV is restricted, and mitral valve replacement surgery is the procedure of choice. As degenerative MS patients frequently have multimorbidities that elevate their risks, clinical treatment should be attempted initially; mitral valve replacement surgery is indicated only in cases that do not respond to clinical treatment.<xref ref-type="bibr" rid="B213"><sup>213</sup></xref> There are reports of small series of percutaneous implants of mitral prostheses in degenerative MS patients, with relative success.<xref ref-type="bibr" rid="B214"><sup>214</sup></xref></p>
            <table-wrap id="t73">
              <table frame="hsides" rules="groups">
                <colgroup width="33%">
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <th align="left" valign="top" colspan="3">Medical treatment of elderly mitral stenosis patients</th>
                  </tr>
                  <tr>
                    <th align="left" valign="middle">Recommendation</th>
                    <th align="center" valign="top">Grade of recommendation</th>
                    <th align="center" valign="top">Level of evidence</th>
                  </tr>
                </thead>
                <tbody style="border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <td align="left" valign="top">Regardless of severity, MS patients who have AF, be it permanent, persistent, or paroxysmal, should receive warfarin indefinitely, with the aim of keeping INR between 2 and 3, unless this is contraindicated</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">MS patients indicated for warfarin may use direct oral anticoagulants</td>
                    <td align="center" valign="top">IIb</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Elderly rheumatic MS patients should receive prophylaxis to prevent rheumatic fever</td>
                    <td align="center" valign="top">III</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Elderly MS patients with MVA less than or equal to 1.5 cm<sup>2</sup>; FC II, III, or IV; and/or signs of RVF should receive loop diuretics to alleviate symptoms</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Elderly MS patients with MVA less than or equal to 1.5 cm<sup>2</sup>; FC II, III, or IV; and SR, who continue to be symptomatic in spite of diuretic use, if HR is over 60 bpm, should receive beta-blockers, unless there are contraindications</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Elderly patients with mild MS who develop AF with elevated ventricular response should receive beta-blockers to control ventricular response, unless there are contraindications</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">In the previously described cases, nondihydropyridine calcium channel blockers or digitalis may be used, in the event that beta-blockers are contraindicated</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">MS patients with signs of RVF and hepatomegaly, without adequate response to loop diuretics, should receive spironolactone.</td>
                    <td align="center" valign="top">IIb</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN37a">
                  <p><italic>AF: atrial fibrillation; bpm: beats per minute; FC: New York Heart Association functional class; HR: heart rate; INR: international normalized ratio; MS: mitral stenosis; MVA: mitral valve area; RVF: right ventricle failure; SR: sinus rhythm</italic>.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
            <table-wrap id="t74">
              <table frame="hsides" rules="groups">
                <colgroup width="33%">
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <th align="left" valign="top" colspan="3">Indications for intervention in elderly rheumatic mitral stenosis patients</th>
                  </tr>
                  <tr>
                    <th align="left" valign="middle">Recommendation</th>
                    <th align="center" valign="top">Grade of recommendation</th>
                    <th align="center" valign="top">Level of evidence</th>
                  </tr>
                </thead>
                <tbody style="border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <td align="left" valign="top">Elderly symptomatic rheumatic MS patients (FC II-IV), with MVA &#8804; 1.5 cm<sup>2</sup>, who have favorable valve morphology and no contraindications, should undergo PBMV</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">A</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Elderly rheumatic MS patients who, although they are very symptomatic (FC III/IV) with MVA &#8804; 1.5 cm<sup>2</sup>, but with unfavorable valve morphology or contraindication to PBMV, without elevated surgical risk or low life expectancy, should be referred for open valvuloplasty or valve replacement surgery</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">If the MS patient is in FC II with MVA &#8804; 1.5 cm<sup>2</sup>, but is not a candidate for PBMV, it is prudent to maintain medical treatment as long as the patient does not become more symptomatic</td>
                    <td align="center" valign="top">IIb</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Rheumatic MS patients with MVA &#8804; 1.5 cm<sup>2</sup> who are indicated for AVR, ascending aorta surgery, or MRS, should also undergo valvuloplasty or mitral valve replacement</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">PBMV is indicated for rheumatic MS patients, with MVA &#8804; 1.5 cm<sup>2</sup>, even if they are asymptomatic, notwithstanding pulmonary arterial hypertension (PASP &gt; 50 mmHg), whose probably etiology is MS, when valve morphology is favorable, in the absence of contraindication</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Severe rheumatic MS patients (MVA &#8804; 1.0 cm<sup>2</sup>), who are asymptomatic and who have favorable valve morphology for PBMV and no contraindications, should undergo the procedure</td>
                    <td align="center" valign="top">IIb</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN38a">
                  <p><italic>AVR: aortic valve replacement; FC: New York Heart Association functional class; MS: mitral stenosis; MRS: myocardial revascularization surgery; MVA: mitral valve area; PASP: pulmonary artery systolic pressure; PBMV: percutaneous balloon mitral valvuloplasty</italic>.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
            <table-wrap id="t75">
              <table frame="hsides" rules="groups">
                <colgroup width="33%">
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <th align="left" valign="top" colspan="3">Indications for intervention in elderly degenerative mitral stenosis patients</th>
                  </tr>
                  <tr>
                    <th align="left" valign="middle">Recommendation</th>
                    <th align="center" valign="top">Grade of recommendation</th>
                    <th align="center" valign="top">Level of evidence</th>
                  </tr>
                </thead>
                <tbody style="border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <td align="left" valign="top">MVR in elderly degenerative MS patients who do not respond adequately to clinical treatment and who have low surgical risk and high life expectancy</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">PBMV in elderly degenerative MS patients, FC III/IV, who do not respond to clinical treatment, with high surgical risk</td>
                    <td align="center" valign="top">IIb</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Percutaneous implants of mitral prosthesis in very symptomatic patients who do not respond to clinical treatment and who are not candidates for open surgery or PBMV</td>
                    <td align="center" valign="top">IIb</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN39a">
                  <p><italic>FC: New York Heart Association functional class; MS: mitral stenosis; MVR: mitral valve replacement; PBMV: percutaneous balloon mitral valvuloplasty</italic>.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </sec>
        </sec>
        <sec>
          <title>6.2. Mitral Regurgitation</title>
          <sec>
            <title>6.2.1. Diagnostic Peculiarities</title>
            <p>From the etiological point of view, mitral regurgitation (MR) may be: (a) primary: when there are histological changes in the valve, for example, myxomatous degeneration, degenerative fibroelastic disease, and IE; or (b) secondary: when MR is functional and the valve is histologically normal, for example, poor leaflet coaptation with dilated cardiomyopathy. MR is common in elderly patients; the degenerative cause is the most frequent, followed by ischemia, and, less frequently, rheumatic disease and IE.<xref ref-type="bibr" rid="B215"><sup>215</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B216"><sup>216</sup></xref> Acute MR is mainly linked to CAD by papillary muscle dysfunction or chordae tendineae rupture, with condition of acute HF.</p>
            <p>Symptoms &#8211; symptoms of chronic MR are related to severity, rate of disease progression, pulmonary BP, presence of arrhythmias (e.g., AF), and associated diseases. The most common symptoms are stress dyspnea and fatigue.</p>
            <p>Physical examination &#8211; The following are present: protosystolic murmur in mitral focus, variable intensity, and displaced ictus, with characteristics of volumetric overload. Thoracic deformities, which are common at this age, may modify ictus, sounds, and murmurs.<xref ref-type="bibr" rid="B102"><sup>102</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B202"><sup>202</sup></xref></p>
            <p>Complementary exams &#8211; During EKG, frequent abnormalities are LAO, AF and left ventricular overload (LVO).<xref ref-type="bibr" rid="B217"><sup>217</sup></xref> In the presence of ischemic MR, electrocardiographic signs of coronary insufficiency, such as electrically inactive zones and alterations in ventricular repolarization, may occur.<xref ref-type="bibr" rid="B218"><sup>218</sup></xref> In cases of acute MR, EKG may be normal, or it may show only sinus tachycardia.<xref ref-type="bibr" rid="B217"><sup>217</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B219"><sup>219</sup></xref> Chest radiography aids detection of comorbidities, evaluation of pulmonary congestion, and distinction between acute and chronic cases. In cases of acute MR, the heart may have normal dimensions, and pulmonary congestion may, nevertheless, be present. In cases of chronic MR, there will be an increase in the LA and LV.<xref ref-type="bibr" rid="B217"><sup>217</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B218"><sup>218</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B220"><sup>220</sup></xref> Transthoracic echocardiography is indispensable for diagnosing and evaluating degree of mitral regurgitation, chamber size, and ventricular function. The sizes of the LA and LV and measurements of pulmonary artery pressure are especially important. Identification of the cause and detailed evaluation of valvular apparatus impairment, leaflet morphology, and reflux mechanism are important for deciding whether the most adequate treatment is mitral valve replacement or plasty.<xref ref-type="bibr" rid="B202"><sup>202</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B221"><sup>221</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B222"><sup>222</sup></xref> Transesophageal echocardiography (TEE) may be used when there are technical difficulties to acquiring an adequate echocardiography window. Cardiac catheters are indicated for diagnosis of CAD in patients referred for surgery and in cases where there are doubts regarding the severity of the lesion.<xref ref-type="bibr" rid="B102"><sup>102</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B202"><sup>202</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B221"><sup>221</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B222"><sup>222</sup></xref> ET/ergospirometry may be used to evaluate the reproduction of symptoms and changes in tolerance to exercise. They are less used with very elderly patients with physical limitations.<xref ref-type="bibr" rid="B202"><sup>202</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B217"><sup>217</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B221"><sup>221</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B222"><sup>222</sup></xref> Magnetic resonance and computerized tomography are not routinely used in patients with mitral disease, but they may be indicated when the severity of MR or LV function have not been adequately evaluated by echocardiogram or when there are discrepancies.<xref ref-type="bibr" rid="B221"><sup>221</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B222"><sup>222</sup></xref></p>
          </sec>
          <sec>
            <title>6.2.2. Treatment Peculiarities</title>
            <p>Treatment of MR should consider its etiology and severity. AF, pulmonary hypertension, and symptoms are relevant factors in the decision making process. Elderly patients &gt; age 75 have elevated surgical risks. Surgical management in this age range will aim to improve and maintain quality of life. Thus, the symptoms present are a determining factor for surgical indication. Patients with ventricular dysfunction who are asymptomatic should continue clinical treatment.<xref ref-type="bibr" rid="B221"><sup>221</sup></xref> Therapeutic decisions for MR should be guided by presentation (acute or chronic), clinical hemodynamic profile, and severity of symptoms. Echocardiography parameters, such as LVEF, left ventricular end-systolic diameter (LVESD), and the presence of dyspnea are indicators for surgical therapy (See the following recommendations table). Mitral plasty is the preferred surgical treatment. Currently, mitral clips are an incipient and promising alternative.<xref ref-type="bibr" rid="B221"><sup>221</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B223"><sup>223</sup></xref></p>
            <p>Treatment of acute MR &#8211; In patients with acute, severe MR, immediate surgical treatment is recommended. Some patients with moderate MR may develop hemodynamic compensation due to LV dilation, thus making lower filling pressure and normalization of cardiac output possible. In cases of chordae tendineae rupture, mitral repair is preferable to mitral replacement, and surgery may be scheduled according to the patient&#8217;s clinical and hemodynamic status.<xref ref-type="bibr" rid="B221"><sup>221</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B223"><sup>223</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B224"><sup>224</sup></xref> Medical treatment of acute MR must by implemented as a support therapy for the definitive surgical correction.<xref ref-type="bibr" rid="B221"><sup>221</sup></xref> In the presence of severe manifestations, such as acute pulmonary edema or shock, vasoactive drugs, such as intravenous vasodilators, sodium nitroprusside, nitroglycerin, and vasopressin amines, in addition to an intra-aortic balloon for hemodynamic support, should be used up to the moment of the indicated surgical procedure.<xref ref-type="bibr" rid="B223"><sup>223</sup></xref></p>
            <p>Treatment of chronic MR &#8211; Patients with chronic, asymptomatic MR and normal LVEF are not indicated for medical treatment. There is no evidence that long-term treatment with vasodilators presents therapeutic benefits.<xref ref-type="bibr" rid="B221"><sup>221</sup></xref> In symptomatic patients, treatment with ACEI, beta-blockers, such as carvedilol, and diuretics should be implemented.<xref ref-type="bibr" rid="B224"><sup>224</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B225"><sup>225</sup></xref> Biventricular pacemakers in patients classified as &#8220;responders&#8221; show improvements in MR in reverse LV geometry.<xref ref-type="bibr" rid="B226"><sup>226</sup></xref> Patients with symptomatic chronic primary MR should undergo surgical treatment, preferably plasty, regardless of LV function. Asymptomatic patients who have progressive dysfunction (LVEF &lt; 0.60) and/or increased ventricular diameters (LVESD &gt; 45 mm), should also be considered surgery. Indication for valve surgery in elderly patients &gt; age 75 has not been consistently evaluated in clinical trials, it being necessary to prioritize the presence of symptoms as an indication for invasive intervention. In valve replacement surgery, bioprostheses are indicated in elderly patients owing to their lower rates of prosthetic dysfunction and to the inherent risks of anticoagulant therapy.<xref ref-type="bibr" rid="B227"><sup>227</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B228"><sup>228</sup></xref></p>
            <p>Percutaneous treatment of mitral regurgitation &#8211; Percutaneous treatment of MR has been performed, particularly in Europe. In Brazil, MitraClip&#174; is the only commercially available device, and it is used only in select cases, owing to the high cost. The use of this device is indicated in patients whose primary chronic MR is degenerative in etiology and whose surgical risks are high or prohibitive. Furthermore, patients with chronic MR secondary to ventricular dilation who are refractory to optimized clinical treatment and cardiac resynchronization may eventually benefit from this procedure. In symptomatic patients with severe MR due to degeneration of a bioprosthesis or previously implanted valve rings and prohibitive surgical risks, percutaneous mitral replacement via the valve-in-valve procedure at a specialized center is an alternative. Percutaneous mitral replacement for symptomatic patients with severe native valve MR and prohibitive surgical risks is at an advanced phase of development and should be available in Brazil in the coming years.<xref ref-type="bibr" rid="B229"><sup>229</sup></xref></p>
            <table-wrap id="t76">
              <table frame="hsides" rules="groups">
                <colgroup width="33%">
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <th align="left" valign="top" colspan="3">Recommendations for MR surgery</th>
                  </tr>
                  <tr>
                    <th align="left" valign="middle">Recommendation</th>
                    <th align="center" valign="top">Grade of recommendation</th>
                    <th align="center" valign="top">Level of evidence</th>
                  </tr>
                </thead>
                <tbody style="border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <td align="left" valign="top">Symptomatic patients with severe acute MR</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Symptomatic patients with severe chronic primary MR and normal left ventricular function</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Asymptomatic patients severe chronic primary MR and left ventricular function (EF 30-60% and/or end-systolic diameter &#8805; 40 mm)</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Plasty is preferable to mitral replacement in severe chronic primary MR patients</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Plasty or mitral replacement is indicated in patients with severe chronic primary MR and patients undergoing concomitant heart surgery</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Mitral replacement is preferable to plasty in patients with chronic secondary MR of ischemic etiology</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">A</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Mitral plasty may be considered for chronic primary (non-rheumatic) MR, normal ventricular function, and new atrial fibrillation or pulmonary hypertension (resting PASP &gt; 50 mmHg)</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Plasty or mitral replacement may be considered for symptomatic patients with chronic primary MR and FE &#8804; 30%</td>
                    <td align="center" valign="top">IIb</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Mitral plasty via catheter may be considered for symptomatic patients (FC III/IV) with chronic primary MR and prohibitive surgical risk</td>
                    <td align="center" valign="top">IIb</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Mitral plasty may be considered for symptomatic patients (FC III/IV) with chronic secondary (functional) MR who are refractory to clinical treatment and cardiac resynchronization</td>
                    <td align="center" valign="top">IIb</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">For symptomatic patients with severe MR due to degeneration of a bioprosthesis or previously implanted valve rings and prohibitive surgical risks, percutaneous mitral replacement at a specialized center may be considered</td>
                    <td align="center" valign="top">IIb</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Asymptomatic patients with severe MR and preserved left ventricular function (LVEF &gt; 60% and end systolic diameter &lt; 40 mm)</td>
                    <td align="center" valign="top">III</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Plasty or mitral replacement may be considered for patients with moderate MR who are undergoing concomitant myocardial revascularization surgery</td>
                    <td align="center" valign="top">III</td>
                    <td align="center" valign="top">A</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN40a">
                  <p><italic>EF: ejection fraction; FC: New York Heart Association functional class; LVEF: left ventricular ejection fraction; MR: mitral regurgitation; PASP: pulmonary artery systolic pressure</italic>.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </sec>
        </sec>
        <sec>
          <title>6.3. Aortic Stenosis</title>
          <sec>
            <title>6.3.1. Diagnostic Peculiarities</title>
            <p>In order to diagnose AS, the most frequent valvulopathy in elderly patients, it is necessary to consider clinical history, which may be difficult in this age range due to possible cognitive and sensory alterations.</p>
            <p>Symptoms &#8211; Patients may be asymptomatic or present dyspnea, angina pectoris, or syncope.</p>
            <p>Physical examination &#8211; Findings may include: (a) impulsive type <italic>ictus cordis</italic>, which may be absent in elderly patients due to increased anteroposterior diameter of the rib cage; (b) the <italic>parvus et tardus</italic> pulse (reduced amplitude and longer duration time), which is characteristic of AS in younger patients, may be absent in elderly patients, due to the stiffening of arterial walls which promotes an increase in PWV, thus masking this semiological finding; (c) mid-systolic murmur in crescendo and decrescendo which radiates toward the neck and clavicles. Gallavardin&#8217;s phenomenon is frequently auscultated. This is a radiation of the AS murmur to the apical region; (d) hypophonetic second sound.</p>
            <p>Complementary exams &#8211; EKG may present findings compatible with LAO and LVO. Chest radiography may be normal, in approximately half of elderly patients examined, or there may be aspects of hypertrophy, which may or may not present post-stenotic aortic dilatation. Echocardiography is a fundamental exam for diagnosing and classifying this valvulopathy. Three echocardiography parameters are frequently used to classify severity of AS: (a) peak aortic jet velocity; (b) mean transvalvular gradient; (c) valve area (<xref ref-type="table" rid="t77">Table 9</xref>). The ET has been indicated for asymptomatic patients with severe AS in order to verify the hemodynamic response to effort; on the other hand, its use in elderly patients should be individualized, owing to the presence of multimorbidities which may impede the procedure.</p>
            <table-wrap id="t77">
              <label>Table 9</label>
              <caption>
                <title>Diagnosis and classification of aortic stenosis severity</title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup width="25%">
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <th align="left" valign="top">Indicator</th>
                    <th align="center" valign="top">Mild</th>
                    <th align="center" valign="top">Moderate</th>
                    <th align="center" valign="top">Severe</th>
                  </tr>
                </thead>
                <tbody style="border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <td align="left" valign="top">Jet velocity (m/s)</td>
                    <td align="center" valign="top">&lt; 3.0</td>
                    <td align="center" valign="top">3.0 to 4.0</td>
                    <td align="center" valign="top">&gt; 4.0</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Mean gradient (mmHg)</td>
                    <td align="center" valign="top">&lt; 25</td>
                    <td align="center" valign="top">25 to 40</td>
                    <td align="center" valign="top">&gt; 40</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Valve area (cm<sup>2</sup>)</td>
                    <td align="center" valign="top">&gt; 1.5</td>
                    <td align="center" valign="top">1.0 to 1.5</td>
                    <td align="center" valign="top">&lt; 1.0</td>
                  </tr>
                </tbody>
              </table>
            </table-wrap>
          </sec>
          <sec>
            <title>6.3.2. Treatment Peculiarities</title>
            <p>Medical treatment &#8211; Arterial hypertension is common in elderly AS patients. It contributes to increased total afterload, in conjunction with obstruction, thus promoting LV overload. In elderly patients, it is necessary to begin antihypertensive treatment with low doses and gradually increase posology. It is necessary to be cautious when using diuretics, due to the risk of hypotension. ACEI may be advantageous due to their effect on ventricular fibrosis, and beta-blockers are appropriate in patients with CAD. Statin use is not indicated for preventing the progression of AS.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref> In the presence of HF, beta-blockers should be initiated with low doses, and the same precautions should be taken in prescribing aldosterone antagonists, ACEI, and ARB, and especially with digitalis drugs, as their toxicity and therapeutic thresholds are close.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref> In elderly patients, it is important to evaluate creatinine clearance in order to adjust dosages and thus avoid drug intoxication.</p>
            <p>Surgical treatment &#8211; Indicating surgery, whether aortic valve replacement or transcatheter aortic valve implantation (TAVI), depends on a set of factors, including: severity of valve lesion; complementary exam data; evaluation of multimorbidities; risk scores, for example the STS score; and functional evaluation (frailty and cognitive function). Deciding on percutaneous implantation requires a multidisciplinary team for integrated action.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B230"><sup>230</sup></xref> The first step in deciding on surgery is establishing that the patient has a severe aortic valve lesion, which, associated with the presence of symptoms, presents a high grade of recommendation. Surgical treatment may still be offered to asymptomatic patients with ventricular dysfunction (LVEF &lt; 50%) or who have already scheduled another cardiac surgery.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref> In relation to the risks of surgical procedures, patients are classified as low risk: STS &lt; 4%, without frailty, without comorbidity; intermediate risk: STS 4% to 8%, mild frailty, affected organic system; high risk: STS &gt; 8%, moderate to severe frailty, more than 2 affected organic systems; prohibitive risk: pre-operative risk &gt; 50% in 1 year, 3 affected organic systems, or extreme frailty.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B231"><sup>231</sup></xref> In most cases, the decision is complex, making it necessary to involve family and the medical and multidisciplinary team and, above all, to respect the patient&#8217;s own wishes. When the benefits are considered less than the risks, palliative care may be the patient&#8217;s best option.</p>
            <table-wrap id="t78">
              <table frame="hsides" rules="groups">
                <colgroup width="33%">
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <th align="left" valign="top" colspan="3">Recommendations for medical treatment of AS</th>
                  </tr>
                  <tr>
                    <th align="left" valign="middle">Recommendation</th>
                    <th align="center" valign="top">Grade of recommendation</th>
                    <th align="center" valign="top">Level of evidence</th>
                  </tr>
                </thead>
                <tbody style="border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <td align="left" valign="top">Systemic arterial hypertension should be treated in asymptomatic AS patients, starting with a low dose of anti-hypertensive and gradually increasing, as necessary, with frequent clinical follow-up</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Vasodilator therapy may be used in association with invasive hemodynamic monitoring to treat patients with severe decompensated AS, with New York Heart Association class IV symptoms of HF</td>
                    <td align="center" valign="top">IIb</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Statin use is not indicated to prevent the progression of AS in patients with mild to moderate calcified lesions</td>
                    <td align="center" valign="top">III</td>
                    <td align="center" valign="top">A</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN41a">
                  <p><italic>AS: aortic stenosis, HF: heart failure</italic>.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
            <table-wrap id="t79">
              <table frame="hsides" rules="groups">
                <colgroup width="33%">
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <th align="left" valign="top" colspan="3">Recommendations for surgical treatment of AS</th>
                  </tr>
                  <tr>
                    <th align="left" valign="middle">Recommendation</th>
                    <th align="center" valign="top">Grade of recommendation</th>
                    <th align="center" valign="top">Level of evidence</th>
                  </tr>
                </thead>
                <tbody style="border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <td align="left" valign="top">Symptomatic patients with severe AS</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Asymptomatic patients with severe AS and LVEF &lt; 50%</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Patients with severe AS scheduled to undergo other cardiac surgeries</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Asymptomatic patients with very severe AS (transvalvular jet velocity &#8805; 5.0 m/s) and low surgical risk</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Asymptomatic patients with severe AS and diminished exercise tolerance or</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">effort hypotension</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Patients with moderate AS scheduled to undergo other cardiac surgeries</td>
                    <td align="center" valign="top">IIb</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN42a">
                  <p><italic>AS: aortic stenosis; LVEF: left ventricular ejection fraction</italic>.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
            <table-wrap id="t80">
              <table frame="hsides" rules="groups">
                <colgroup width="33%">
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <th align="left" valign="top" colspan="3">The choice between surgical aortic valve replacement and TAVI</th>
                  </tr>
                  <tr>
                    <th align="left" valign="middle">Recommendation</th>
                    <th align="center" valign="top">Grade of recommendation</th>
                    <th align="center" valign="top">Level of evidence</th>
                  </tr>
                </thead>
                <tbody style="border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <td align="left" valign="top">Surgical aortic valve replacement is recommended in patients who have indications for surgical treatment and who have low or intermediate surgical risks</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">A</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">In patients under consideration for TAVI and in those with high surgical risk for valve replacement, members of a Heart Team should collaborate to provide the patient with the best care possible</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">TAVI is recommended for patients indicated for surgical aortic valve replacement, with prohibitive surgical risk and post-TAVI life expectancy of more than 12 months</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">TAVI is a reasonable alternative to surgical aortic valve replacement in patients who meet indications for surgical treatment and who have high surgical risks</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Balloon aortic valvuloplasty may be considered as a bridge to surgical or percutaneous valve replacement in severely symptomatic patients with severe aortic stenosis</td>
                    <td align="center" valign="top">IIb</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">TAVI is not recommended for patients whose existent comorbidities would impede the benefits expected from correction of aortic stenosis</td>
                    <td align="center" valign="top">III</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN43a">
                  <p><italic>TAVI: transcatheter aortic valve implantation</italic>.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </sec>
        </sec>
        <sec>
          <title>6.4. Aortic Regurgitation</title>
          <sec>
            <title>6.4.1. Diagnostic Peculiarities</title>
            <p>AR is less common in elderly patients than AS and MR.</p>
            <p>Etiology &#8211; The most common causes of chronic AR in elderly patients are ascending aorta dilation due to SAH, primary aortic disease, calcified valve disease, and, rarely, atrioventricular block (AVB). Another cause is rheumatic cardiac disease (especially in developing countries).<xref ref-type="bibr" rid="B232"><sup>232</sup></xref></p>
            <p>Symptoms &#8211; Chronic AR evolves slowly and insidiously in most cases, with very low morbidity during the asymptomatic phase. After this phase, some patients present progression of the regurgitant lesion, with subsequent LV dilation, systolic dysfunction, and, eventually, HF.<xref ref-type="bibr" rid="B233"><sup>233</sup></xref> Mortality rates for patients with severe AR with NYHA class II symptoms are approximately 6% yearly and almost 25% in patients in NYHA classes III or IV.<xref ref-type="bibr" rid="B234"><sup>234</sup></xref></p>
            <p>Physical examination &#8211; The murmur is diastolic, decrescendo, blowing, and high frequency, and it is best heard in the left sternal border or in aortic focus. Its severity is more related to duration of murmur than to intensity. The ictus is dislocated, revealing LV volumetric overload, and its dimension is related to lesion severity. Peripheral alterations, which are characteristics of severity in young patients (increased PP, arterial neck pulsation, and systolic pulsation in the head), may be exacerbated in elderly patients, given that alterations resulting from the loss of elasticity of the great arteries may accentuate them.</p>
            <p>Complementary exams &#8211; EKG is not very specific in AR, and the routine finding is LVO in cases with long duration. Chest radiography helps detect comorbidities, evaluate pulmonary congestion, and distinguish between acute and chronic cases. Acute cases present pulmonary congestion and normal or slightly enlarged cardiac area. Chronic cases present increased cardiac area secondary to LV dilation. Ascending aorta dilation, on the other hand, suggests that the AR is secondary to aneurysmal dilatation of the aorta. Echocardiography is the pillar of serial monitoring and evaluation of chronic AR patients. It is useful for confirming diagnosis, evaluating cause and valve morphology, estimating lesion severity, and evaluating LV dimensions, mass, and systolic function, as well as aortic root dimensions.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref> For patients with suspected moderate or severe AR, cardiovascular magnetic resonance (CMR) provides precise quantification of regurgitant volume and fraction, in addition to precise measurements of LV volumes and function. CMR is particularly useful when the degree of LV dilatation in echocardiography seems to be greater than what would be expected. Cardiac catheterization should be performed routinely in all patients referred for surgical correction or coronary disease evaluation, or when clinical and laboratory tests are unclear or divergent regarding AR severity.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref></p>
          </sec>
          <sec>
            <title>6.4.2. Treatment Peculiarities</title>
            <p>In cases of severe acute AR, surgical treatment should be implemented as early as possible, especially if there are signs and symptoms of low cardiac output. In these cases, clinical treatment is inferior to surgical treatment. Inotropic drugs and vasodilators may aid clinical control while the patient is waiting for surgery.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B235"><sup>235</sup></xref></p>
            <p>Clinical treatment &#8211; Clinical treatment of AR patients with vasodilators is applied to those with associated SAH and those with severe symptomatic AR and high surgical risks, especially owing to comorbidities, in order to alleviate symptoms. They are not routinely recommended for patients with mild, moderate, or severe asymptomatic chronic AR and normal systolic function.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B235"><sup>235</sup></xref> Studies have not demonstrated the efficacy of these drugs in slowing surgical indication in AR patients, and they do not substitute surgery when it is indicated.<xref ref-type="bibr" rid="B236"><sup>236</sup></xref></p>
            <p>Surgical treatment &#8211; Patients with severe symptomatic AR, as well as some asymptomatic patients, have reduced quality of life and life expectancy without surgical treatment. Selecting the appropriate moment for and type of procedure is paramount for a satisfactory surgical result; it is, naturally, necessary to observe and respect functionality and associated comorbidities in this group of patients.<xref ref-type="bibr" rid="B235"><sup>235</sup></xref> Surgical treatment is indicated for patients with severe symptomatic AR or for asymptomatic patients with reduced LVEF or significant LV dilatation.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B235"><sup>235</sup></xref> There has recently been some speculation regarding aortic valve repair for this pathology, given that complications resulting from anticoagulant use in patients who receive mechanical prostheses are not uncommon. Scientific studies have demonstrated that valve repair is an independent predictor of better survival, with a great reduction in the need for reoperation.<xref ref-type="bibr" rid="B237"><sup>237</sup></xref> Few centers, however, have the experience necessary to perform this procedure, and, in elderly patients, thickened, deformed, or calcified leaflets are common findings, which complicate the procedure.<xref ref-type="bibr" rid="B203"><sup>203</sup></xref></p>
            <p>Percutaneous treatment &#8211; Percutaneous aortic valve implantation is an effective option for AR patients with moderate or high risks for conventional valve replacement surgery. The use of TAVI is still off-label for AR patients, but studies have demonstrated that it is feasible and will be able to be a treatment alternative.<xref ref-type="bibr" rid="B238"><sup>238</sup></xref></p>
            <table-wrap id="t81">
              <table frame="hsides" rules="groups">
                <colgroup width="33%">
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <th align="left" valign="top" colspan="3">Recommendations for surgical treatment of aortic regurgitation</th>
                  </tr>
                  <tr>
                    <th align="left" valign="middle">Recommendation</th>
                    <th align="center" valign="top">Grade of recommendation</th>
                    <th align="center" valign="top">Level of evidence</th>
                  </tr>
                </thead>
                <tbody style="border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <td align="left" valign="top">Symptomatic patients with severe AR, regardless of LV systolic function</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Asymptomatic patients, with severe AR and LVEF &lt; 50%</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Patients with severe AR scheduled to undergo other cardiac surgeries</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Asymptomatic patients with severe AR, normal LV systolic function (LVEF &#8805; 50%), and significant LF dilatation (LVSD &gt; 50 mm)</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Patients with moderate AR scheduled to undergo other cardiac surgeries</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Asymptomatic patients with severe AR, normal LV systolic function (LVEF &gt; 50%), progressive severe LV dilatation (LVEDD &gt; 65 mm), and low surgical risk</td>
                    <td align="center" valign="top">IIb</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN44a">
                  <p><italic>AR: aortic regurgitation; LV: left ventricle; LVEDD: left ventricular end-diastolic diameter; LVEF: left ventricular ejection fraction; LVSD: left ventricular systolic diameter</italic>.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </sec>
        </sec>
        <sec>
          <title>6.5. Infective Endocarditis</title>
          <sec>
            <title>6.5.1. Diagnostic Peculiarities</title>
            <p>IE, which was previously prevalent in young and middle-aged patients, owing to its association with rheumatic valve disease, has progressively increased in the elderly population.<xref ref-type="bibr" rid="B239"><sup>239</sup></xref> In Europe and the United States, more than half of cases occur in patients &gt; age 60. Diagnosis of IE in elderly patients may be more difficult owing to the fact that signs and symptoms such as mental confusion, fatigue, weight loss, and murmur may be attributed to age itself. The forms in which IE is present in elderly patients, such as clinical signs of stroke, HF, pneumonia, and abdominal pain, may also confuse the initial diagnosis. In some case registries, fever appears in only 2% of cases in elderly patients, in comparison with 90% of patients &lt; age 60. Other not very specific symptoms, such as anorexia, weight loss, arthralgia, dyspnea, and headache, similarly appear in elderly patients. Classic peripheral signs of IE such as Osler&#8217;s nodes, Roth spots, and petechiae, are less frequent in elderly patients, being found in 1% to 14% of cases.<xref ref-type="bibr" rid="B240"><sup>240</sup></xref></p>
            <p>Laboratory and echocardiography data &#8211; hemogram may be normal or present leucocytosis, with the frequent presence of normochromic, normocytic anaemia. Erythrocyte sedimentation rate (ESR) may be elevated in 90% of cases. Positive rheumatoid factor is found in 50% of cases, and the majority of patients have proteinuria and microscopic hematuria.<xref ref-type="bibr" rid="B241"><sup>241</sup></xref> Blood cultures: at least 3 blood samples should be collected during the first 24 hours, with intervals of less than 15 minutes between samples, and they must be collected before beginning antibiotic therapy, given that antibiotic use is the leading cause of failure to identify the germ responsible for endocarditis. In the most developed countries, blood cultures reach 80% to 95% positivity. Echocardiogram: with the advent of echocardiography in the 1980&#8217;s,<xref ref-type="bibr" rid="B242"><sup>242</sup></xref> the probability of diagnosing IE has increased, given that it is used to confirm the presence of vegetations, which are one of the 3 diagnostic pillars of IE, along with identification of the germ in blood culture and signs of affected valves, such as murmurs. In elderly patients, the sensitivity and specificity of transthoracic echocardiography is lower owing to the higher frequency of calcified lesions and valve prostheses, as well as the presence of obesity and thoracic deformities.<xref ref-type="bibr" rid="B243"><sup>243</sup></xref> TEE improves diagnostic accuracy, and it may be performed in elderly patients as safely as in younger patients.</p>
            <p>Diagnostic criteria &#8211; In various cases of IE, diagnosis is uncertain due to the impossibility of demonstrating the existence of vegetations and to unspecific clinical manifestations, resulting in diagnostic errors. The Duke criteria, modified by Li et al.<xref ref-type="bibr" rid="B244"><sup>244</sup></xref> (<xref ref-type="table" rid="t82">Table 10</xref>), are the most widely used to establish IE diagnosis. Nevertheless, IE diagnosis is a difficult process, but the inclusion of clinical, laboratory, and echocardiography data reduces the chance of error.</p>
            <table-wrap id="t82">
              <label>Table 10</label>
              <caption>
                <title>Criteria for diagnosing IE</title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup width="50%">
                  <col/>
                  <col/>
                </colgroup>
                <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <th align="center" valign="top" colspan="2">Major criteria</th>
                  </tr>
                  <tr>
                    <th align="left" valign="top">Microbiological</th>
                    <th align="center" valign="top">Comments</th>
                  </tr>
                </thead>
                <tbody style="border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <td align="left" valign="top">Typical isolated microorganism from two separate blood cultures: <italic>Streptococcus viridans</italic>, <italic>Streptococcus bovis</italic>, HACEK group, <italic>Staphylococcus aureus</italic>, or community-acquired enterococcal bacteremia, in the absence of a primary focus</td>
                    <td align="center" valign="top">In patients with possible IE, at least 2 blood cultures must be obtained in 2 different veins during the first 2 hours. In patients with septic shock, 3 blood cultures must be collected at 5&#8211;10 min intervals, after which point empirical antibiotic therapy should be initiated.</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top" colspan="2">Or</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top" colspan="2">Persistently positive blood cultures consistent with isolated IE</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top" colspan="2">Or</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Blood culture positive for <italic>Coxiella burnetii</italic> or antibody titre (lgG) &gt; 1:800 for <italic>C. burnetii</italic></td>
                    <td align="center" valign="top"><italic>C. burnetii</italic>is not cultivated in most laboratory analyses</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top" colspan="2">Evidence of endocardial involvement</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top" colspan="2">New valvular regurgitation (increases and changes in preexisting murmurs are not sufficient)</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top" colspan="2">Or</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Positive echocardiogram (TEE recommended for patients with prostheses, possible IE based on clinical criteria, or complicated IE)</td>
                    <td align="center" valign="top">Three TTE findings are considered major criteria: discrete oscillating intracardiac mass located on a valve or subvalvular structure, periannular abscess, and new dehiscence of prosthetic valve</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">
                      <bold>Minor criteria</bold>
                    </td>
                    <td align="center" valign="top">
                      <bold>Comments</bold>
                    </td>
                  </tr>
                  <tr>
                    <td align="left" valign="top" rowspan="5">Predisposition to IE, including certain heart conditions and IV drug use</td>
                  </tr>
                  <tr>
                    <td align="center" valign="top">Cardiac abnormalities that are associated with IE are classified into 3 groups:</td>
                  </tr>
                  <tr>
                    <td align="center" valign="top">&#9679; High risk: previous IE, aortic valve disease, rheumatic valve disease, prosthetic valve, coarctation of the aorta, and complex cyanotic heart diseases</td>
                  </tr>
                  <tr>
                    <td align="center" valign="top">&#9679; Medium risk: mitral valve prolapse with leaflet insufficiency or thickening, isolated mitral stenosis, tricuspid valvulopathy, pulmonary stenosis, hypertrophic cardiomyopathy</td>
                  </tr>
                  <tr>
                    <td align="center" valign="top">&#9679; Low risk: Ostium secundum IAC, ischemic disease, previous revascularization surgery, and mitral valve prolapse without previous regurgitation, and mitral valve prolapse without regurgitation and with thin leaflets</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Fever</td>
                    <td align="center" valign="top">Temperature &gt; 38&#176; C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top" rowspan="2">Vascular phenomena</td>
                    <td align="center" valign="top">Except petechiae and hemorrhagic suffusions</td>
                  </tr>
                  <tr>
                    <td align="center" valign="top">No peripheral lesions are pathognomonic of IE</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Immunologic phenomena</td>
                    <td align="center" valign="top">Rheumatoid factor, glomerulonephritis, Osler nodes, Roth spots</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Microbiological findings</td>
                    <td align="center" valign="top">Positive blood cultures that do not meet major criteria. Serological evidence of active infection, isolation of coagulase-negative staphylococci and organisms that rarely cause IE are excluded from this category</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top" colspan="2">Cases are clinically defined as &#8220;definite IE&#8221; if they meet 2 major criteria, 1 major criterion and 3 minor criteria, or 5 minor criteria and &#8220;possible IE&#8221; if they meet 1 major criterion and 1 minor criterion or 3 minor criteria.</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN20">
                  <p>HACEK: Haemophilus aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens and Kingella kingae; IAC: interatrial communication; IE: infective endocarditis; IgG: immunoglobulin G; IV: intravenous; TEE: transesophageal echocardiography; TTE: transthoracic echocardiography.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </sec>
          <sec>
            <title>6.5.2. Treatment Peculiarities</title>
            <p>As the population ages, IE affects more and more elderly individuals. More than a third of IE patients in Western countries are over age 70.<xref ref-type="bibr" rid="B245"><sup>245</sup></xref> Mortality in elderly patients is also higher when compared to the general population.<xref ref-type="bibr" rid="B246"><sup>246</sup></xref> Aging is a heterogeneous process, and it is always recommended to use AGA, which considers nutritional, functional, and cognitive status to better define prognosis as well as treatment options for this population.<xref ref-type="bibr" rid="B247"><sup>247</sup></xref> The majority of elderly IE patients have multimorbidities, and the most common entryways for bacteria are the digestive and urinary tracts. Furthermore, these patients have predisposing factors, such as AS, valve prostheses, and intracardiac devices.<xref ref-type="bibr" rid="B248"><sup>248</sup></xref> In defining treatment, the international literature makes no considerations regarding age and its consequences for treatment choice.<xref ref-type="bibr" rid="B248"><sup>248</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B250"><sup>250</sup></xref> AGA data and the presence of frailty syndrome are factors which should be considered in deciding on a proposed treatment.<xref ref-type="bibr" rid="B207"><sup>207</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B240"><sup>240</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B250"><sup>250</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B251"><sup>251</sup></xref> <xref ref-type="table" rid="t83">Table 11</xref> shows examples of possible adaptations for elderly patients. The majority of elderly patients have decreased renal function; nephrotoxic antibiotics should, thus, be used carefully and, in some cases, even avoided in this population.<xref ref-type="bibr" rid="B252"><sup>252</sup></xref> Treatment of IE often entails prolonged hospital stay, which is associated with functional and cognitive decline in the elderly population. The use of outpatient parenteral antibiotic therapy should be encouraged in this population, thus avoiding the complications of prolonged hospital stay; this requires that the patient&#8217;s infection be controlled and the clinical situation stabilized, in addition to long-term venous access. In the event of difficult venous access, the subcutaneous or even the oral route may be considered, depending on the antibiotic in use.<xref ref-type="bibr" rid="B252"><sup>252</sup></xref> Regarding surgical treatment, the indications are the same as in the general population (severe valvular lesion with HF, large vegetation with a risk of systemic embolism, and uncontrolled infection); in this context, however, AGA becomes more important in deciding on surgical treatment due to the fact that the risks of existing multimorbidities may interfere with the planned procedures. In these cases, a careful risk-benefit assessment of the procedures must be performed in an individualized manner.<xref ref-type="bibr" rid="B253"><sup>253</sup></xref> When surgery is indicated, the decision should be made in a multidisciplinary fashion, and, when possible, it should involve the opinion of an infectologist, cardiologist, cardiac surgeon, anesthesiologist, and geriatrician, in order to define patients who may or may not benefit from a surgical procedure with the highest possible accuracy.<xref ref-type="bibr" rid="B252"><sup>252</sup></xref></p>
            <table-wrap id="t83">
              <label>Table 11</label>
              <caption>
                <title>Adaptations of the 2015 guidelines for elderly patients in accordance with comorbidities and functional status<xref ref-type="bibr" rid="B252"><sup>252</sup></xref></title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup width="33%">
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <th align="center" valign="top"/>
                    <th align="center" valign="top">Guidelines</th>
                    <th align="center" valign="top">Suggestion for elderly patients</th>
                  </tr>
                </thead>
                <tbody style="border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <td align="left" valign="top">Transesophageal echocardiography</td>
                    <td align="center" valign="top">Consider in all cases, in accordance with clinical suspicion</td>
                    <td align="center" valign="top">Assess risk-benefit of the procedure</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Aminoglycosides</td>
                    <td align="center" valign="top">Combined to penicillin or vancomycin as first choice</td>
                    <td align="center" valign="top">Avoid, due to nephrotoxicity. Evaluate alternatives</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Vancomycin</td>
                    <td align="center" valign="top">First-line treatment in beta-lactam allergic patients or in cases of MRSA</td>
                    <td align="center" valign="top">Consider daptomicine to avoid nephrotoxicity</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Monitoring of antibiotic serum levels</td>
                    <td align="center" valign="top">Vancomycin and aminoglycosides</td>
                    <td align="center" valign="top">Consider also for all beta-lactam antibiotics</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Intravenous therapy</td>
                    <td align="center" valign="top">All cases</td>
                    <td align="center" valign="top">Consider oral or subcutaneous route</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Outpatient parenteral therapy</td>
                    <td align="center" valign="top">Only in compliant patients who have easy access to a hospital</td>
                    <td align="center" valign="top">Consider for patients for whom prolonged hospital stay may be deleterious to functional and cognitive status</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN21">
                  <p>MRSA: Methicillin-resistant Staphylococcus aureus. Adapted from Forestier et al., 2016.<xref ref-type="bibr" rid="B252"><sup>252</sup></xref></p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </sec>
        </sec>
      </sec>
      <sec>
        <title>7. Cardiac Arrhythmias</title>
        <p>Arrhythmias and conduction disorders are common in elderly patients, and they are an important cause of emergency room visits and hospitalization in this age group.<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> Structural alterations in the cardiovascular system, which are promoted by aging and are associated with a higher incidence of comorbidities such as LVH, CAD, degenerative valvulopathy, SAH, LV dysfunction, and pulmonary disease, in addition to polypharmacy, are responsible for the increased prevalence of arrhythmias in this population.<xref ref-type="bibr" rid="B254"><sup>254</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B258"><sup>258</sup></xref> Clinical evaluation should be meticulous, as many elderly patients have atypical manifestations such as unexplained falls, intermittent mental confusion, thromboembolic events, and syncope; some are even asymptomatic and are casually detected during routine EKG.<xref ref-type="bibr" rid="B257"><sup>257</sup></xref> Multimorbidities, frailty syndrome, and impaired functionality and cognitive function interfere with the management of arrhythmias in this group, which should be individualized.</p>
        <p>This section will discuss the diagnostic and treatment peculiarities of the main cardiac arrhythmias in elderly patients.</p>
        <sec>
          <title>7.1. Syncope and Bradyarrhythmias</title>
          <sec>
            <title>7.1.1. Syncope and its Differential Diagnoses in Elderly Patients</title>
            <p>Syncope has a multifactorial etiology in elderly patients. Postural hypotension, also known as orthostatic hypotension (OH) is common, secondary to medication use and severe arrhythmias. It has an average prevalence of 6%, increasing exponentially with age.<xref ref-type="bibr" rid="B254"><sup>254</sup></xref> It has a recurrence rate of 25% to 30% per year, in the first 2 years.<xref ref-type="bibr" rid="B255"><sup>255</sup></xref> It is an independent predictor of morbimortality, reduced functional capacity and institutionalization,<xref ref-type="bibr" rid="B257"><sup>257</sup></xref> as well as a frequent cause of hospital admission. Cardiogenic syncope has the worst prognoses, accounting for up to 20% of cases in elderly patients.<xref ref-type="bibr" rid="B258"><sup>258</sup></xref> Bradyarrhythmias (sinus node disease or advanced AVB) are commonly related to syncope in elderly patients. Tachyarrhythmias manifest with syncope less frequently; they are &#8220;on-off&#8221; type manifestations, with sudden onset and without short-duration prodromes. They are unrelated to orthostatic position and characterized by fast recovery. It is worthwhile to remember that AS is a possible cause of effort-induced syncope in elderly patients. The following are considered to be predictors of cardiogenic syncope, according to the Evaluation of Guidelines in Syncope Study 2 (EGSYS-2) score: EKG abnormalities, structural heart disease, palpitations before syncope, syncope during effort or in the supine position, absence of autonomic prodromes, and absence of triggering or precipitating factors (&#8805; 3 points suggest cardiogenic syncope).<xref ref-type="bibr" rid="B259"><sup>259</sup></xref> The presence of dyspnea before syncope also suggests cardiogenic etiology.<xref ref-type="bibr" rid="B258"><sup>258</sup></xref> Syncope due to postural hypotension is common in dehydrated patients and patients with diminished intravascular volume. Its prevalence increases with age, varying from 6% in population studies to 70% in hospitalized, institutionalized, or Parkinson&#8217;s disease patients.<xref ref-type="bibr" rid="B260"><sup>260</sup></xref> In patients with dementia, 48% of syncope episodes occur due to OH.<xref ref-type="bibr" rid="B261"><sup>261</sup></xref> Syncope episodes up to 2 hours after a meal should lead to a diagnosis of postprandial hypotension. Neuromediated syncope is common in elderly patients, of which the most prevalent types are situational (associated with urination, defecation, coughing, and carotid sinus hypersensitivity).<xref ref-type="bibr" rid="B258"><sup>258</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B259"><sup>259</sup></xref> The presence of nausea, blurred vision, and sweating suggests a non-cardiogenic cause (OH or neurocardiogenic).<xref ref-type="bibr" rid="B258"><sup>258</sup></xref> Neurological syncope, due to preexisting bilateral vertebrobasilar insufficiency is often accompanied by symptoms such as vertigo and ataxia, and it has a lower prevalence. It is also necessary to consider syncope an atypical manifestation of severe diseases such as AMI, which occurs in 3% of elderly patients &gt; age 65<xref ref-type="bibr" rid="B262"><sup>262</sup></xref> and is common in patients &gt; age 85 with prevalence reaching 20%,<xref ref-type="bibr" rid="B263"><sup>263</sup></xref> as well as of pulmonary thromboembolism (PTE) (24% of elderly patients &gt; age 65)<xref ref-type="bibr" rid="B264"><sup>264</sup></xref> and acute aortic dissection (5% to 10%).<xref ref-type="bibr" rid="B265"><sup>265</sup></xref></p>
            <sec>
              <title>7.1.1.1. Stratifying Risk of Death</title>
              <p>The San Francisco Syncope Rules (SFS) are simple rules that evaluate risk of adverse events in syncope patients. It has 74% to 98% sensitivity and 56% specificity.<xref ref-type="bibr" rid="B266"><sup>266</sup></xref> The low specificity is owing to the fact that it is not very specific for cardiogenic syncope, but it makes it possible to discharge low-risk patients and hospitalize more severe cases. The following mnemonic device is used for the SFS:</p>
              <disp-quote>
                <p>C &#8211; History of CHF.</p>
                <p>H &#8211; Hematocrit &lt; 30%.</p>
                <p>E &#8211; EKG abnormalities.</p>
                <p>S &#8211; Shortness of breath.</p>
                <p>S &#8211; SBP at admission &lt; 90 mmHg.</p>
                <p>(A) &#8211; Age &gt; 75.</p>
              </disp-quote>
              <p>In a patient with syncope, any one of these findings is considered a high risk for events such as death, AMI, arrhythmia, PTE, stroke, subarachnoid hemorrhage, or emergency room re-admission and hospitalization related to a new syncope episode. When age is included, sensitivity increases to 100%, while specificity is reduced.</p>
              <p>In conjunction with the SFS, the Short-Term Prognosis of Syncope (STePS) Study is another useful score,<xref ref-type="bibr" rid="B267"><sup>267</sup></xref> which evaluates the risk of events 10 days after a syncope episode. It includes only 4 independent risk factors:</p>
              <list list-type="bullet">
                <list-item>
                  <p>EKG abnormalities (the best predictor).</p>
                </list-item>
                <list-item>
                  <p>Concomitant trauma.</p>
                </list-item>
                <list-item>
                  <p>Absence of prodromes.</p>
                </list-item>
                <list-item>
                  <p>Male sex.</p>
                </list-item>
              </list>
              <p>Predictors of poor long-term (1-year) prognosis include: EKG abnormalities, ventricular arrhythmia, HF, and age &gt; 45. The 1-year event rate (severe arrhythmia or death) varies from 0% for patients with none of the 4 risk factors to 27% in patients with &#8805; 3 factors. We may, thus, consider a high risk of short-term (7 to 10 days) and long-term (1 year) events for elderly patients who have syncope and:</p>
              <list list-type="bullet">
                <list-item>
                  <p>Are male.</p>
                </list-item>
                <list-item>
                  <p>Do not have prodromes and have syncope with concomitant trauma.</p>
                </list-item>
                <list-item>
                  <p>Have dyspnea or sustained hypotension associated with the syncopal event.</p>
                </list-item>
                <list-item>
                  <p>Have previous diagnosis of HF and/or ventricular arrhythmias.</p>
                </list-item>
                <list-item>
                  <p>Have altered EKG at admission.</p>
                </list-item>
              </list>
            </sec>
            <sec>
              <title>7.1.1.2. General Recommendations</title>
              <p>Elderly patients with unexplained recurrent falls, which are not witnessed by third parties and which are associated with trauma, should be interpreted as possible cardiogenic syncope. Investigation should occur in a hospital environment for episodes which occurred &lt; 1 week prior, with trauma or in patients with known heart disease. Patients with a single episode, which occurred &gt; 1 week prior, without trauma, may be investigated as outpatients. All elderly patients &gt; age 75 with previous heart disease diagnosis and abnormal EKG should be investigated in a hospital environment, due to the high probability of cardiogenic syncope. The flowchart in <xref ref-type="fig" rid="f4">Figure 2</xref> suggests investigation routes, based on risk stratification, clinical history, and physical examination, which will define investigation strategy and treatment.</p>
              <fig id="f4">
                <label>Figure 2</label>
                <caption>
                  <title>Flowchart for investigating syncope in elderly patients. SFS: San Francisco Syncope Rules.</title>
                </caption>
                <graphic xlink:href="1678-4170-abc-112-05-0649-90086-gf02-en.tif"/></fig>
            </sec>
          </sec>
          <sec>
            <title>7.1.2. Diagnostic Peculiarities of Bradyarrhythmias</title>
            <p>First-degree AVB have a prevalence of 6% to 8% in individuals &#8805; age 70, and, like Mobitz I second-degree AVB, they are not predictive of cardiovascular events. Mobitz II second-degree AVB and third-degree AVB, on the other hand, have worse prognoses and require treatment. Extreme bradycardia (&lt; 35 bpm), sinus pauses &gt; 2 seconds, and advanced AVB are associated with structural heart disease, and they are frequently symptomatic. The association of bradycardia induced by negative chronotropic drugs, acetylcholinesterase or anticholinesterase inhibitors (rivastigmine, donepezil, and galantamine) and central alpha-blockers used for prostatic symptoms or SAH is common. Many cases are asymptomatic and are casually diagnosed during a routine check-up, especially in sedentary patients or patients with functional limitations.<xref ref-type="bibr" rid="B268"><sup>268</sup></xref> Common symptoms include non-rotatory dizziness, effort-induced dyspnea or fatigue, caused by chronotropic deficit. The classic &#8220;on-off&#8221; syncope (Stokes-Adams syndrome) caused by total or intermittent high-degree AVB is an alert symptom.<xref ref-type="bibr" rid="B269"><sup>269</sup></xref> Diagnosis may be performed via 12-derivation EKG, 24-h Holter, loop event monitor, and electrophysiological studies (EPS). Holter is indicated for bradycardia patients who have daily symptoms. Event monitors (implantable or portable) are indicated for detecting symptoms which occur rarely, but which have significant hemodynamic impairment and prolonged duration and which place the elderly patient&#8217;s life at risk.<xref ref-type="bibr" rid="B270"><sup>270</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B274"><sup>274</sup></xref> In cases of effort-induced symptoms, treadmill ET may clarify diagnostic suspicion (chronotropic incompetence or advanced degree of AVB). EPS is indicated for patients with inconclusive 24-h Holter or loop monitor results and unexplained recurrent syncope.</p>
            <table-wrap id="t84">
              <table frame="hsides" rules="groups">
                <colgroup width="33%">
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <th align="left" valign="top" colspan="3">General recommendations for diagnosing bradyarrhythmias in elderly patients</th>
                  </tr>
                  <tr>
                    <th align="left" valign="middle">Recommendation</th>
                    <th align="center" valign="top">Grade of recommendation</th>
                    <th align="center" valign="top">Level of evidence</th>
                  </tr>
                </thead>
                <tbody style="border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <td align="left" valign="top">12-derivation EKG for patients with suspected bradyarrhythmia</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Investigate negative chronotropic drug use and effort-induced symptoms in asymptomatic patients with bradycardia</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">24-h Holter for electrocardiographic correlation of symptoms with bradycardia (pre-syncope, syncope, palpitations, effort dyspnea, fatigue disproportionate to effort, or non-rotatory dizziness)</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">24-h Holter for patients with resting sinus bradycardia, asymptomatic patients</td>
                    <td align="center" valign="top">IIb</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">24-h Holter for patients with resting sinus bradycardia with effort symptoms to evaluate advanced degrees of block or pauses</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">24-h Holter for patients with high-degree AVB or total intermittent AVB, asymptomatic patients without negative chronotropic drugs</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">24-h Holter for patients with syncope, pre-syncope, and dizziness, whose probable cause (with the exception of bradyarrhythmias) has been identified, but whose symptoms persist in spite of treatment of the probably cause, and patients recovered from CRA</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">24-h Holter for electrocardiographic correlation of unspecific symptoms such as rotatory dizziness, dyspnea, and sweating in patients with documented bradycardia</td>
                    <td align="center" valign="top">III</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">24-h Holter for patients with dizziness</td>
                    <td align="center" valign="top">III</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">7-day Holter or loop monitor for patients with infrequent pre-syncope, syncope, palpitations, effort dyspnea, fatigue disproportionate to effort, or non-rotatory dizziness</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">7-day Holter or loop monitor for patients with infrequent syncope, pre-syncope, and dizziness, whose probable cause (with the exception of bradyarrhythmias) has been identified but whose symptoms persist in spite of treatment of the probably cause</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">7-day Holter or loop monitor for electrocardiographic correlation of unspecific symptoms such as rotatory dizziness, dyspnea, and sweating in patients without documented bradycardia</td>
                    <td align="center" valign="top">III</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Treadmill ergometric test for patients with effort-induced symptoms and resting sinus bradycardia to evaluate de chronotropic incompetence</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Treadmill ergometric test for patients without symptoms and resting sinus bradycardia</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Electrophysiological study for patients with clinical suspicion of bradyarrhythmia and inconclusive non-invasive exams to measure AH intervals, HV intervals, and sinus node recovery time (investigating sinus node disease and degenerative disease of the AV node)</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN45a">
                  <p><italic>AVB: atrioventricular block; CRA: cardiorespiratory arrest; EKG: electrocardiogram</italic>.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </sec>
          <sec>
            <title>7.1.3. Treatment Peculiarities</title>
            <p>Treating syncope &#8211; Syncope treatment in elderly patients must be multifactorial, with an approach that covers various components which may be involved in the syncopal episode. Cases of cardiogenic syncope in no way differ from the approach used in younger patients. Treatment of baseline heart disease is in accordance with specific recommendations, respecting the elderly patient&#8217;s specificities.<xref ref-type="bibr" rid="B254"><sup>254</sup></xref> It is necessary to avoid hypovolemia and substitute vasodilatadory medications which may promote OH, by accentuating the dysautonomic response, such as beta-blockers with alpha and beta blocking action, calcium channel blockers, and central alpha-blockers. Centrally acting drugs (tricyclics, fluoxetine, aceprometazine, haloperidol, L-dopa, et al.) are also associated with risk of syncope and should be substituted.<xref ref-type="bibr" rid="B275"><sup>275</sup></xref> The non-pharmacological measures commonly prescribed to treat neuromediated syncope have conflicting results in the elderly population, and they also present difficulties in adherence. Not limiting sodium intake and stimulating water intake are effective, but with low adhesion.<xref ref-type="bibr" rid="B276"><sup>276</sup></xref> Avoiding heavy meals and meals in hot environments, as well as standing up immediately after a meal, may reduce the occurrence of postprandial hypotension. Classical medical treatment of neuromediated syncope has also not been shown to be effective in the elderly.<xref ref-type="bibr" rid="B277"><sup>277</sup></xref> Regarding drugs, fludrocortisone has proven efficacy in this age range, at the expense of more collateral effects, mainly edema, hypokalemia, metabolic alkalosis, weight gain, and supine hypertension.<xref ref-type="bibr" rid="B277"><sup>277</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B278"><sup>278</sup></xref> Treatment of cardioinhibitory syncope with pacemakers was shown to reduce syncope recurrence in a randomized clinical trial carried out in the elderly population (5% versus 61% recurrence in the pacemaker and control groups, respectively, p = 0.00000).<xref ref-type="bibr" rid="B279"><sup>279</sup></xref></p>
            <p>Treating bradyarrhythmias &#8211; Treatment of bradyarrhythmias in the elderly follows the same recommendations as in younger patients.<xref ref-type="bibr" rid="B280"><sup>280</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B281"><sup>281</sup></xref> The suspension of negative chronotropic drugs is fundamental. In patients with symptomatic sinus bradycardia, resting HR &lt; 40 bpm, or symptomatic pauses, indicating definitive pacemaker implant reduces symptoms and improves quality of life, but it does not interfere with prognosis.<xref ref-type="bibr" rid="B282"><sup>282</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B283"><sup>283</sup></xref> In patients with sinus bradycardia and dementia who need to initiate cholinesterase inhibitors, this may aggravate their bradyarrhythmia, the effect being dose dependent. Indication for a pacemaker in these patients should be individualized, as there is no evidence regarding the efficacy of this approach. In patients with advanced AVB, indication for a definitive pacemaker is associated with reduced mortality and should follow the same indications as in younger patients.<xref ref-type="bibr" rid="B280"><sup>280</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B281"><sup>281</sup></xref></p>
            <p>General recommendations &#8211; With relation to treating syncope and bradyarrhythmias in the elderly, multiprofessional evaluation is important regarding the functional aspect and prognosis of comorbidities. Generally speaking, there is no specificity regarding the treatment efficacy of interventions with respect to bradyarrhythmias, and the same treatment recommendations used for younger patients should be followed. It is necessary to be attentive to non-cardiovascular use of drugs with negative chronotropic properties, as they may aggravate preexisting bradycardia.</p>
          </sec>
        </sec>
        <sec>
          <title>7.2. Tachyarrhythmias in Elderly Patients</title>
          <sec>
            <title>7.2.1. Diagnostic Peculiarities</title>
            <p>Supraventricular tachyarrhythmias (SVT) &#8211; SVT are frequent in elderly patients, and their prevalence increases with age. The most common in this age range are: atrial tachycardia, flutter, and AF.<xref ref-type="bibr" rid="B284"><sup>284</sup></xref> Atrial extrasystoles (AES) in patients ages 60 to 86 have an approximate prevalence of 80%, and supraventricular paroxysmal tachycardia (SVPT) has a prevalence from 10% to 15%. In individuals &#8805; age 80, the prevalence of AES may reach 100%, and that of SVPT is from 25% to 30%. Effort-induced atrial arrhythmias in patients &gt; age 80 reach a prevalence of &gt; 10%.<xref ref-type="bibr" rid="B285"><sup>285</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B286"><sup>286</sup></xref> In spite of their high prevalence, SVT (with the exception of AF) are not associated with increased morbimortality.<xref ref-type="bibr" rid="B285"><sup>285</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B286"><sup>286</sup></xref> AES and non-sustained SVT (duration &lt; 30 seconds) are not very symptomatic, observed with palpitation, &#8220;lightheadedness,&#8221; dizziness, neck pounding, and &#8220;shortness of breath.&#8221; Occasionally, dyspnea, chest pain, and syncope may occur, especially in patients with acute sustained arrhythmias, significant diastolic dysfunction, severe AS, HF, or CAD. The higher the HR, the less tolerated the arrhythmia, as a consequence of reduced cardiac output, which results in manifestations of cerebral and myocardial ischemia, arterial hypotension, and pulmonary congestion.<xref ref-type="bibr" rid="B287"><sup>287</sup></xref></p>
            <p>Some arrhythmias are peculiar in elderly patients:<xref ref-type="bibr" rid="B288"><sup>288</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B289"><sup>289</sup></xref></p>
            <list list-type="bullet">
              <list-item>
                <p>Atrial tachycardia with AVB: presents high atrial frequency associated with slow ventricular response due to an AVB. Digitalis toxicity and hypokalemia are common causes.</p>
              </list-item>
              <list-item>
                <p>Multifocal atrial tachycardia: is common in the presence of COPD.<xref ref-type="bibr" rid="B285"><sup>285</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B287"><sup>287</sup></xref> Treatment focuses on the baseline disease, considering pre-fibrillatory rhythm.</p>
              </list-item>
              <list-item>
                <p>Accelerated junctional rhythm: digitalis toxicity and inferior wall AMI are the most common causes in elderly patients.<xref ref-type="bibr" rid="B285"><sup>285</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B287"><sup>287</sup></xref> Diagnosis is suggested for regular bradycardic rhythm, in the presence of AF.</p>
              </list-item>
              <list-item>
                <p>Atrial flutter: habitually indicates structural heart disease. CAD and COPD are the most common causes in elderly patients. Elderly patients with atrial flutter have a higher chance of degeneration to AF; they are at a high risk for thromboembolic events, and they should receive a similar approach to AF cases.</p>
              </list-item>
            </list>
            <p>Ventricular tachyarrhythmias &#8211; Ventricular extrasystoles are common in the elderly, with an incidence of 70% to 90%.<xref ref-type="bibr" rid="B284"><sup>284</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B287"><sup>287</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B288"><sup>288</sup></xref> They do not generally produce symptoms, unless they are very frequent. Symptomology is variable; patients may perceive repetitive heart beats or the sensation that their &#8220;heart is going to stop,&#8221; due to compensatory pauses. They are associated with risk of death in the presence of structural heart diseases. Treating arrhythmia in an isolated manner, however, does not reduce risk in elderly patients with CAD.<xref ref-type="bibr" rid="B286"><sup>286</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B289"><sup>289</sup></xref> Pre-syncope, syncope, low output, pulmonary congestion, behavior disorder, and disorientation are frequent clinical manifestations of poor prognosis. Ventricular tachycardia (VT) is frequently associated with structural heart disease. LVH is an important determinant of ventricular arrhythmia,<xref ref-type="bibr" rid="B287"><sup>287</sup></xref> as well as HF, which increases the incidence of VT from 2% to 4%, in patients without HF, to 20% to 80%.<xref ref-type="bibr" rid="B287"><sup>287</sup></xref> In these patients, the presence of complex ventricular arrhythmia is associated with an increase in total mortality, cardiac mortality, and sudden death. The worse the ventricular dysfunction, the more complex and severe the ventricular arrhythmia will be. Thus, patients with LV dysfunction or LVH with complex ventricular arrhythmia should be considered at a high risk of sudden death, even if they are asymptomatic. In elderly patients without heart disease, the finding of tachyarrhythmias on Holter has no prognostic implications.<xref ref-type="bibr" rid="B286"><sup>286</sup></xref></p>
            <p>Based on these premises, with respect to diagnostic evaluation of tachyarrhythmias in elderly patients, these Guidelines recommend:</p>
            <table-wrap id="t85">
              <table frame="hsides" rules="groups">
                <colgroup width="33%">
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <th align="left" valign="middle">Recommendation</th>
                    <th align="center" valign="top">Grade of recommendation</th>
                    <th align="center" valign="top">Level of evidence</th>
                  </tr>
                </thead>
                <tbody style="border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <td align="left" valign="top">Inquiry about all medications in use and risk analysis of induced arrhythmias or prolonged QT</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">12-derivation EKG in all patients at each clinical visit, even in the absence of symptoms</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Calculation of QTc interval for all patients who report palpitation</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Calculation of QT interval for all patients with polymorphic VT</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">24-h Holter to evaluate symptoms of palpitation, syncope, and unexplained falls</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">24-h Holter for asymptomatic patients with normal LV function and EKG with LVH</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">24-h Holter for asymptomatic patients with depressed LV function and EKG with LVH</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">A</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">24-h Holter for patients recovered from VF/VT before hospital discharge</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">24-h Holter for patients recovered from VF/VT during outpatient follow-up to evaluate therapy efficacy</td>
                    <td align="center" valign="top">IIb</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">24-h Holter for asymptomatic patients with simple ventricular arrhythmia during the initial exam, with normal LV function and EKG with LVH, during outpatient follow-up to evaluate therapy efficacy</td>
                    <td align="center" valign="top">III</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">24-h Holter for asymptomatic patients with complex ventricular arrhythmia during the initial exam, with normal LV function and EKG with LVH, during outpatient follow-up to evaluate therapy efficacy</td>
                    <td align="center" valign="top">IIb</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">24-h Holter for asymptomatic patients with simple ventricular arrhythmia during the initial exam, with depressed LV function and EKG with LVH, during outpatient follow-up to evaluate therapy efficacy</td>
                    <td align="center" valign="top">III</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">24-h Holter for asymptomatic patients with complex ventricular arrhythmia during the initial exam, with depressed LV function and EKG with LVH, during outpatient follow-up to evaluate therapy efficacy</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">24-h Holter for asymptomatic patients with normal LV function and EKG</td>
                    <td align="center" valign="top">III</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Ergometric test in patients without contraindications who have effort-induced palpitations</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Ergometric test in patients without contraindications who have palpitations associated with chest angina</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Ergometric test in patients without contraindications who have resting palpitations</td>
                    <td align="center" valign="top">III</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Ergometric test in asymptomatic patients without contraindications to investigate arrhythmia</td>
                    <td align="center" valign="top">III</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Echocardiogram in all patients with palpitations</td>
                    <td align="center" valign="top">IIb</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Echocardiogram in patients with LVH on EKG, asymptomatic patients</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Echocardiogram in patients with palpitation and dyspnea</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Echocardiogram in patients with LVH and cardiac murmur, asymptomatic patients</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Investigation of ischemic etiology in all patients with supraventricular tachycardia</td>
                    <td align="center" valign="top">III</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Investigation of ischemic etiology in all patients with supraventricular tachycardia and angina</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Investigation of ischemic etiology in all patients with complex ventricular tachycardia</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Magnetic resonance in patients with complex ventricular arrhythmia, whose other exam results are normal, to investigate arrhythmogenic RV dysplasia, myocardial fibrosis, and asymmetric apical hypertrophy</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Magnetic resonance in all patients with VT</td>
                    <td align="center" valign="top">III</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Magnetic resonance in all patients with SVT</td>
                    <td align="center" valign="top">III</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">EPS in patients with high SD risks (unexplained syncope and complex ventricular arrhythmia on Holter or trifascicular block, in order to clarify syncope etiology)</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN46a">
                  <p><italic>EKG: electrocardiogram; EPS: electrophysiological study; LV: left ventricle; LVH: left ventricular hypertrophy; RV: right ventricle; SD: sudden death; SVT: supraventricular tachyarrhythmia; VF: ventricular fibrillation; VT: ventricular tachycardia</italic>.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </sec>
          <sec>
            <title>7.2.2. Treatment Peculiarities</title>
            <p>Treatment principles for tachyarrhythmias in the elderly are similar to those in younger patients; however, treatment is more frequently influenced by the presence of baseline heart diseases such as CAD, LV dysfunction, LVH, and comorbidities such as chronic renal insufficiency (CRI) and COPD.<xref ref-type="bibr" rid="B290"><sup>290</sup></xref> Non-sustained atrial arrhythmias (supraventricular extrasystoles and atrial tachycardias), generally, do not require treatment. In most cases, they are associated with baseline respiratory diseases, whose treatment, associated with avoiding stimulants such as caffeine, cigarettes, soft drinks, black tea, and fast-acting beta-agonist drugs, is normally sufficient to reduce the number of events and symptoms. Otherwise, the use of calcium channel blockers in patients with COPD (contraindicated in cases of LV dysfunction) or beta-blockers (in low doses and selectively, such as bisoprolol or metoprolol), in patients without contraindication, may be indicated. SVPT is usually caused by reentrant mechanisms, and may be interrupted by vagal maneuvers, such as the Valsalva maneuver, coughing, and vomiting. Due to the risk of arterial embolism, carotid sinus massage should be avoided in all elderly patients unless the presence of significant carotid disease has been excluded. If the attempted vagal maneuvers do not succeed in reversing arrhythmia, chemical cardioversion should be attempted. The first-choice drug should initially be adenosine, with electrocardiographic monitoring. Second-line drugs are calcium channel blockers (verapamil, diltiazem), if LV function is normal, and beta-blockers, in the presence of CAD. Digoxin should be restricted to patients with depressed LV function. In cases that do not respond to first- and second-line agents, class III antiarrhythmic drugs (amiodarone or sotalol) should be used. Beta-blockers and calcium channel blockers are equally effective in maintaining SR and avoiding recurrence of arrhythmia<xref ref-type="bibr" rid="B290"><sup>290</sup></xref> (<xref ref-type="table" rid="t86">Table 12</xref>). In the event of hypotension, signs of low cerebral blood flow, pulmonary congestion, or chest angina, electric cardioversion should be performed at 50 to 75 J. Catheter ablation for treating sustained SVPT whose mechanism is nodal reentrant or an accessory pathway is as effective in elderly patients as it is in younger patients, with a success rate of &gt; 95%.<xref ref-type="bibr" rid="B291"><sup>291</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B295"><sup>295</sup></xref> Elderly patients have a higher risk of complications such as perforation, vascular lesion, renal insufficiency, a higher tendency to develop AF, and thromboembolic events after the procedure. Nevertheless, larger complications occur in &lt; 3% of elderly patients.<xref ref-type="bibr" rid="B292"><sup>292</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B293"><sup>293</sup></xref> It should be considered the treatment of choice for patients with frequent episodes (&gt; 2 events/year, in spite of medical treatment) or patients with contraindications to the previously cited drugs, such as sinus bradycardia, hypotension, broncospasms, and severe LV dysfunction, as well as for patients who do not wish to undergo medical treatment.</p>
            <table-wrap id="t86">
              <label>Table 12</label>
              <caption>
                <title>Drugs used to treat SVPT in elderly patients<xref ref-type="bibr" rid="B290"><sup>290</sup></xref></title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup width="16%">
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <th align="center" valign="middle" colspan="6">Cardioversion in the emergency room</th>
                  </tr>
                  <tr>
                    <th align="center" valign="middle"/>
                    <th align="center" valign="middle">Drug</th>
                    <th align="center" valign="middle">Initial dose</th>
                    <th align="center" valign="middle">Repeat</th>
                    <th align="center" valign="middle">Total dose</th>
                    <th align="center" valign="middle">Precautions</th>
                  </tr>
                </thead>
                <tbody style="border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <td align="left" valign="middle">1<italic>st</italic> choice</td>
                    <td align="center" valign="middle">Adenosine</td>
                    <td align="center" valign="middle">6 mg in rapid bolus IV over 10 seconds</td>
                    <td align="center" valign="middle">12 mg every 15 minutes</td>
                    <td align="center" valign="middle">30 mg</td>
                    <td align="center" valign="middle">Patients with CAD and active bronchial asthma</td>
                  </tr>
                  <tr>
                    <td align="left" valign="middle">2<italic>nd</italic> choice</td>
                    <td align="center" valign="middle">Verapamil</td>
                    <td align="center" valign="middle">5 mg IV over 3 to 5 minutes</td>
                    <td align="center" valign="middle">5 mg after 15 minutes</td>
                    <td align="center" valign="middle">10 mg</td>
                    <td align="center" valign="middle">LV dysfunction and hypotension</td>
                  </tr>
                  <tr>
                    <td align="left" valign="middle">Patients with severe LV dysfunction</td>
                    <td align="center" valign="middle">Amiodarone</td>
                    <td align="center" valign="middle">300 mg IV over 30 minutes diluted in 0.9% saline solution or 100 to 250 mL 5% glucose solution</td>
                    <td align="center" valign="middle">-</td>
                    <td align="center" valign="middle">300 mg in bolus IV and 900 to 1,200 mg over the following 24 h</td>
                    <td align="center" valign="middle">May be associated with digitalis IV to better control HR</td>
                  </tr>
                  <tr>
                    <td align="center" valign="middle" colspan="6">Drugs used for maintenance following reversion to sinus rhythm</td>
                  </tr>
                  <tr>
                    <td align="left" valign="middle" rowspan="2">Calcium channel blockers</td>
                    <td align="center" valign="middle">Diltiazem (start with short half-life formulations and, if tolerated, substitute with extended release formulations, following dose adjustment)</td>
                    <td align="center" valign="middle">30 mg 3&#215;/day</td>
                    <td align="center" valign="middle">Increase the dose by 50% every 14 days, if well tolerated, until the desired resting HR (60 to 70 bpm) has been reached</td>
                    <td align="center" valign="middle">180 to 240 mg/day</td>
                    <td align="center" valign="middle">Use caution with tachycardia-bradycardia syndrome and LV dysfunction</td>
                  </tr>
                  <tr>
                    <td align="center" valign="middle">Verapamil</td>
                    <td align="center" valign="middle">120 mg/day</td>
                    <td align="center" valign="middle">Idem</td>
                    <td align="center" valign="middle">240 mg/day</td>
                    <td align="center" valign="middle">Idem</td>
                  </tr>
                  <tr>
                    <td align="left" valign="middle" rowspan="4">Beta-blockers</td>
                    <td align="center" valign="middle">Metoprolol</td>
                    <td align="center" valign="middle">50 mg/day</td>
                    <td align="center" valign="middle"/>
                    <td align="center" valign="middle"/>
                    <td align="center" valign="middle">200 mg/day</td>
                  </tr>
                  <tr>
                    <td align="center" valign="middle">Atenolol</td>
                    <td align="center" valign="middle">25 mg/day</td>
                    <td align="center" valign="middle"/>
                    <td align="center" valign="middle"/>
                    <td align="center" valign="middle">200 mg/day</td>
                  </tr>
                  <tr>
                    <td align="center" valign="middle">Propranolol (In this order of preference, on account of liposolubility)</td>
                    <td align="center" valign="middle">40 mg/day</td>
                    <td align="center" valign="middle"/>
                    <td align="center" valign="middle">Double the dose until the desired HR of 60 to 70 bpm has been reached</td>
                    <td align="center" valign="middle">240 mg/day</td>
                  </tr>
                  <tr>
                    <td align="center" valign="middle">Carvedilol</td>
                    <td align="center" valign="middle">3.125 mg 2&#215;/day</td>
                    <td align="center" valign="middle"/>
                    <td align="center" valign="middle">Double the dose every 2 weeks</td>
                    <td align="center" valign="middle">25 mg 2&#215;/day</td>
                  </tr>
                  <tr>
                    <td align="left" valign="middle">Digoxin</td>
                    <td align="center" valign="middle">Preferential in patients with HF</td>
                    <td align="center" valign="middle">0.125 mg/day</td>
                    <td align="center" valign="middle">Take care with patients &gt; age 75 and creatinine &gt; 1.5 mg/dL</td>
                    <td align="center" valign="middle"/>
                    <td align="center" valign="middle">0.25 mg/day (In the most elderly patients, debilitated patients, and patients with ERD, the dose should be adjusted in accordance with response and maintained at lower doses to 0.125 mg, 2&#8211;3&#215;/week)</td>
                  </tr>
                  <tr>
                    <td align="left" valign="middle">Amiodarone</td>
                    <td align="center" valign="middle">Pay attention to collateral effects, especially those that are thyroid-related</td>
                    <td align="center" valign="middle">600 mg/day for 10 days</td>
                    <td align="center" valign="middle">Reduce to 400 mg/day for 10 days and maintain 200 mg/day</td>
                    <td align="center" valign="middle">Monitor hepatic function, thyroid function, QTc interval, and eye fundus every 6 months</td>
                    <td align="center" valign="middle">Maintain 100 to 200 mg/day</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN22">
                  <p>DAC: doen&#231;a arterial coronariana; FC: frequ&#234;ncia card&#237;aca; IC: insufici&#234;ncia card&#237;aca; IRC: insufici&#234;ncia renal terminal; IV: via intravenosa; TPSV: taquicardia parox&#237;stica supraventricular; VE: ventr&#237;culo esquerdo.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
            <p>General recommendations &#8211; Treatment of tachyarrhythmias in elderly patients: treatment of tachyarrhythmias in elderly patients, especially those between the ages of 65 and 75, should be similar to that in younger patients. In patients &gt; age 75, individualization of conduct is recommended with multiprofessional evaluation that takes into consideration not only age, but also comorbidities, cognitive function, functional capacity, patient preferences, and severity of symptoms.<xref ref-type="bibr" rid="B296"><sup>296</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B297"><sup>297</sup></xref></p>
          </sec>
        </sec>
        <sec>
          <title>7.3. Atrial Fibrillation</title>
          <sec>
            <title>7.3.1. Diagnostic Peculiarities</title>
            <p>AF is the most common persistent arrhythmia in elderly patients.<xref ref-type="bibr" rid="B298"><sup>298</sup></xref> Its prevalence and incidence double every decade after age 60, affecting as many as 8% to 10% of patients &gt; age 80 and 27% of patients &gt; age 90.<xref ref-type="bibr" rid="B287"><sup>287</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B301"><sup>301</sup></xref> It may occur isolatedly as a consequence of morphological and electrophysiological alterations inherent in aging of the atrial myocardium and sinus node, known as &#8220;isolated AF&#8221; or &#8220;lone atrial fibrillation.&#8221; Truly isolated AF is, however, rare in elderly patients.<xref ref-type="bibr" rid="B302"><sup>302</sup></xref> In general, it is associated with structural heart diseases: CAD, SAH, mitral valvulopathy, and HF.<xref ref-type="bibr" rid="B303"><sup>303</sup></xref> Subclinical hyperthyroidism triples the risk of AF.<xref ref-type="bibr" rid="B300"><sup>300</sup></xref> Patients with clinical hyperthyroidism may present episodes of paroxysmal AF. Other causes of AF in elderly patients include: obstructive sleep apnea-hypopnea syndrome (commonly called paroxysmal AF),<xref ref-type="bibr" rid="B303"><sup>303</sup></xref> sinus node disease, and dilated cardiomyopathy, which are generally associated with AF with low ventricular response. Special attention should be paid to sinus node disease represented by tachycardia-bradycardia syndrome, where recurring paroxysmal AF is observed with a sudden stop followed by a long or asystolic pause, which is a frequent cause of unexplained syncope in the elderly. After adjusting for coexisting CVD, mortality in patients with AF is 1.5 to 1.9 times higher that in patients of the same age without AF.<xref ref-type="bibr" rid="B299"><sup>299</sup></xref> This higher rate of mortality is mainly due to the 4- to 5-fold increase in the occurrence of stroke, a risk which proportionally increases after age 50 (&lt; 1.5% in patients &lt; age 50 and approximately 23.5% in patients &gt; age 80).<xref ref-type="bibr" rid="B304"><sup>304</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B305"><sup>305</sup></xref> Diagnosis of AF in elderly patients is initially made by physical examination, anamnesis, and EKG. As many as 20% of AF diagnoses in elderly patients occur casually, during clinical visits, in patients without complaints, especially in cases of permanent AF and ventricular response &lt; 100 bpm, which occurs on account of concomitant AV nodal disease or use of beta-blockers.<xref ref-type="bibr" rid="B287"><sup>287</sup></xref> The most frequent symptoms in elderly patients are: dyspnea, asthenia, dizziness, easy fatigue, decreased tolerance to exercise, sweating, polyuria, syncope, and palpitation. Permanent AF is related to silent thromboembolic events which, associated with chronic decreased cerebral blood flow and cerebrovascular alterations inherent in aging, are responsible for cognitive and motor impairments, such as slowing, motor incoordination, and dementia, which are initially discrete, but progressive and which may go unnoticed and delay diagnosis.<xref ref-type="bibr" rid="B306"><sup>306</sup></xref></p>
            <table-wrap id="t87">
              <table frame="hsides" rules="groups">
                <colgroup width="33%">
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <th align="left" valign="top" colspan="3">General recommendations regarding AF diagnosis in the elderly</th>
                  </tr>
                  <tr>
                    <th align="left" valign="middle">Recommendation</th>
                    <th align="center" valign="top">Grade of recommendation</th>
                    <th align="center" valign="top">Level of evidence</th>
                  </tr>
                </thead>
                <tbody style="border-bottom: thin solid; border-color: #000000">
                  <tr>
                    <td align="left" valign="top">Inquiry about all medications in use and risk analysis of induced arrhythmias or prolonged QT</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">12-derivation EKG in all patients with irregular rhythm to diagnose AF, even in the absence of symptoms</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">12-derivation EKG in all patients with diagnosis of AF, at each clinical visit</td>
                    <td align="center" valign="top">IIb</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">24-h Holter for evaluation of HR control</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">B</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">24-h Holter as follow-up, after rhythm control, in asymptomatic patients</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">24-h Holter for patients who complain of palpitations and for those with sinus rhythm following rhythm control</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">24-h Holter for patients with sinus rhythm, after stroke, to investigate paroxysmal AF</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Transthoracic echocardiography in all patients with AF, with no prior diagnosis of CHF</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Transthoracic echocardiography in all patients with AF</td>
                    <td align="center" valign="top">IIa</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Transesophageal echocardiography in patients with AF &gt; 48 h, for reversion to SR</td>
                    <td align="center" valign="top">I</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                  <tr>
                    <td align="left" valign="top">Transesophageal echocardiography in patients with AF, after stroke, to investigate emboligenic focus</td>
                    <td align="center" valign="top">IIb</td>
                    <td align="center" valign="top">C</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN47a">
                  <p><italic>AF: atrial fibrillation; CHF: congestive heart failure; EKG: electrocardiogram; HR: heart rate; SR: sinus rhythm</italic>.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </sec>
          <sec>
            <title>7.3.2. Treatment Peculiarities</title>
            <p>Treatment of AF in elderly patients does not differ from that in younger patients. Oral anticoagulation (unless contraindicated) and the elimination of precipitating or reversible factors that induce paroxysmal AF or loss of ventricular frequency control in patients with persistent or permanent AF are the bases of AF treatment in elderly patients.<xref ref-type="bibr" rid="B307"><sup>307</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B308"><sup>308</sup></xref> The decision to control HR or SR should be individualized; however, as an initial routine strategy, rhythm control has no benefits over HR control in asymptomatic patients in this age range.<xref ref-type="bibr" rid="B309"><sup>309</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B310"><sup>310</sup></xref></p>
            <sec>
              <title>7.3.2.1. Heart Rate Control</title>
              <p>Lenient strategies for HR control (target baseline HR &lt; 110 bpm) is as effective for controlling symptoms as restrictive HR control (target resting HR &lt; 80 bpm), except in cases of ventricular dysfunction, where caution is necessary to avoid significant bradycardias (HR &lt; 50 bpm).<xref ref-type="bibr" rid="B311"><sup>311</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B312"><sup>312</sup></xref> Beta-blockers, used alone, manage to adequately control HR in 42% of elderly patients,<xref ref-type="bibr" rid="B312"><sup>312</sup></xref> and they should be the first-choice drug for this purpose. Combination with non-dihydropyridine calcium channel blockers should be used cautiously and only in patients without LV dysfunction. Attention should be paid to the condition worsening or to constipation appearing with their use, notably with verapamil, in addition to bradycardia and inferior member edema. Digoxin is less effective when used alone for controlling HR during effort. It is an acceptable choice for physically inactive patients, patients &gt; age 80, and patients in whom other treatments have been ineffective or are contraindicated, and it should be used with due caution.<xref ref-type="bibr" rid="B311"><sup>311</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B313"><sup>313</sup></xref> In cases of tachycardia-bradycardia syndrome and in patients who do not tolerate pharmacological HR control, pacemaker implant or atrioventricular node ablation followed by pacemaker implant may be indicated.<xref ref-type="bibr" rid="B314"><sup>314</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B315"><sup>315</sup></xref> Rhythm control should be reserved for specific circumstances, particularly when symptoms cannot be contained by HR control, given that it is related to a higher number of hospitalizations due to the collateral effects of antiarrhythmic drugs (AAD) and the complications of invasive procedures, mainly in persistent AF with long duration. The strategy of rhythm control does not dispense with anticoagulation.<xref ref-type="bibr" rid="B316"><sup>316</sup></xref> Control may be via AAD, electric cardioversion, or interventional procedures. Electric cardioversion restores SR and is indicated for acute cases of AF that do not respond to pharmacological therapy and that have hemodynamic instability. The basis for choosing AAD either for chemical cardioversion or for maintenance of rhythm depends on the baseline heart disease and the comorbidities, taking the occurrence of major collateral effects into consideration, due to decreased physiological function and the interactions between multiple medications common in elderly patients. Propafenone, sotalol, and amiodarone may be used for patients with minimal or no structural heart disease, bearing in mind that there is a higher risk of collateral and proarrhythmic effects in elderly patients when using propafenone and sotalol. For patients with structural heart disease (LVH with interventricular septum &gt; 12 mm or coronary disease), sotalol or amiodarone are indicated. Amiodarone is reserved for elderly patients with reduced HF and LVEF.<xref ref-type="bibr" rid="B317"><sup>317</sup></xref> Catheter ablation may be useful in healthy elderly patients who are symptomatic, without many comorbidities, without underlying heart disease, with AF paroxysms, and patients who are refractory to treatment or patients who do not wish to use AAD and who have no renal dysfunction. This procedure should be performed in a center with a great deal of experience.<xref ref-type="bibr" rid="B318"><sup>318</sup></xref></p>
            </sec>
          </sec>
          <sec>
            <title>7.3.3. Oral Anticoagulants in Elderly Atrial Fibrillation Patients</title>
            <p>The most feared complication in AF is thromboembolic events, notably stroke, whose incidence and severity increase with age.<xref ref-type="bibr" rid="B319"><sup>319</sup></xref> It is the cause of up to 25% of strokes in elderly patients.<xref ref-type="bibr" rid="B320"><sup>320</sup></xref> Oral anticoagulant therapy reduces the risk of stroke in elderly patients with non-valvular AF by 64%. It is thus superior to aspirin, which reduces the risk by only 22%, and is no longer recommended for stroke prevention in AF patients.<xref ref-type="bibr" rid="B319"><sup>319</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B320"><sup>320</sup></xref> Double antiplatelet aggregation has not demonstrated benefits for preventing thromboembolic events in patients with AF and is not recommended.<xref ref-type="bibr" rid="B321"><sup>321</sup></xref> The risk of thromboembolism in AF may be calculated using risk factor scores.<xref ref-type="bibr" rid="B322"><sup>322</sup></xref> For evaluation of thromboembolic risk, the congestive heart failure, hypertension, age &#8805; 75, diabetes mellitus, prior stroke, or transient ischemic attack (CHADS<sub>2</sub>) score has been the most used. Its variables are age (&#8805; 75) and the presence of comorbidities (HF, SAH, diabetes mellitus, and previous history of thromboembolism). Thromboembolism is worth 2 points, and the other variables are worth 1. Anticoagulation is indicated for patients with scores &#8805; 2, as they are at a high risk of events.<xref ref-type="bibr" rid="B323"><sup>323</sup></xref> In 2010, the CHA<sub>2</sub>DS<sub>2</sub>-VASc score was proposed, considering a higher risk for female patients over age 65 and patients with peripheral arterial disease (1 point for the following variables: HF, hypertension, age between 65 and 74, diabetes mellitus, and peripheral arterial disease; 2 points for age 75 or over and previous thromboembolic event), resulting in higher scores for more elderly patients, women, and peripheral arterial disease patients. These Guidelines, following the recommendations of the most recent guidelines<xref ref-type="bibr" rid="B324"><sup>324</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B325"><sup>325</sup></xref> for treating AF, recommend the use of the CHA<sub>2</sub>DS<sub>2</sub>-VASc clinical score for defining start of anticoagulation in men with scores of 2 or more and women with score of 3 or more. In low-risk patients (men with scores of 0 and women with scores of 1), we recommend the use of echocardiography parameters, such as increased LA and auricular flow velocity, the presence of moderate to accentuated spontaneous contrast, or LA/auricular thrombus as an additional stratification for CHA<sub>2</sub>DS<sub>2</sub>-VASc. If a patient presents any one of these findings, anticoagulation is indicated.<xref ref-type="bibr" rid="B326"><sup>326</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B327"><sup>327</sup></xref> After defining the risk of a thromboembolic event, it becomes necessary to stratify the risk of bleeding, before beginning anticoagulant therapy. The most used risk score for bleeding during anticoagulation is the HAS-BLED, where a score &gt; 3 indicates a high risk of hemorrhage due to oral anticoagulants and includes, in addition to age range (&gt; 65), variables such as SAH with SBP &gt; 160 mmHg (1 point), renal or hepatic dysfunction (1 point each), prior history of stroke (1 point), bleeding (1 point), labile INR (1 point), and drug or alcohol use (1 point each).<xref ref-type="bibr" rid="B328"><sup>328</sup></xref> Data on the isolated influence of age on the risk of bleeding are conflicting; for this reason, age should not be used to contraindicate anticoagulation.<xref ref-type="bibr" rid="B329"><sup>329</sup></xref> Vitamin K antagonists, especially warfarin, are the pillar of oral anticoagulation in patients with AF, significantly reducing stroke and mortality attributed to AF.<xref ref-type="bibr" rid="B330"><sup>330</sup></xref> Variability of INR with warfarin use depends not only on the dose used, but also on other medications and certain types of foods.<xref ref-type="bibr" rid="B331"><sup>331</sup></xref> In an observational study, labile INR has been described in 21.3% of patients ages 40 to 89,<xref ref-type="bibr" rid="B328"><sup>328</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B329"><sup>329</sup></xref> according to which the risk of INR &#8805; 5 increases by 15% with each 10-year increment. As a result of this greater risk, it is necessary to monitor INR in elderly patients (especially those &gt; age 75) more regularly and at more frequent intervals (grade of recommendation I, level of evidence B). These Guidelines recommend the use of low initial doses for elderly patients &lt; age 85 (3 to 4 mg) and 2.5 mg for elderly patients &#8805; age 85, patients with frailty syndrome, malnutrition, or hepatic disease and moderate to advanced renal insufficiency (creatinine clearance &lt; 30 mL/min). The INR is at 3 days, with a new dose at 7 days, if there is dose adjustment, and 14 days, if the dose remains stable. It is weekly during the first 90 days in patients with greater risks, whatever they may be, &gt; age 85, frailty, hepatic or renal insufficiency, history of falls, cognitive impairment, low level of education, and initial treatment. In other patients, evaluation of INR may occur every 15 days during the first 90 days of treatment, and may be monthly afterwards, in cases with stable INR. Oral anticoagulation with warfarin is, thus, safe in elderly patients, provided that precautions in indication and follow-up are respected. Warfarin is the least expensive oral anticoagulant, and its antagonist (vitamin K) is widely available to reverse the drug&#8217;s anticoagulant effect.</p>
            <p>Recently, non-vitamin K antagonist oral anticoagulants have become available with the advantages of not requiring constant monitoring of blood coagulation and presenting fewer drug interactions. They include direct thrombin inhibitors (dabigatran) and direct inhibitors of factor Xa (rivaroxaban, apixaban, and edoxaban). A meta-analysis of the main randomized clinical trials with non-vitamin K antagonist oral anticoagulants<xref ref-type="bibr" rid="B330"><sup>330</sup></xref> has shown a significantly lower risk of stroke or systemic embolism compared with warfarin (relative risk [RR] = 0.81, 95% confidence interval [95% CI] = 0.73 to 0.91), as well as a lower risk of intracranial bleeding (RR = 0.48, 95% CI = 0.39 to 0.59), but not of major bleeding (RR = 0.86, HF 95% = 0.73 to 1.00). Findings were similar to those described in a second meta-analysis<xref ref-type="bibr" rid="B331"><sup>331</sup></xref> with participants &#8805; age 75. Notwithstanding the clear benefit of non-vitamin K antagonist oral anticoagulants, as well as the fact that they are safer regarding intracranial bleeding, this complication has relatively low rates (&lt; 1%/year) even with warfarin (0.76% to 0.85% with warfarin and 0.26% to 0.49% with non-vitamin K antagonists).<xref ref-type="bibr" rid="B331"><sup>331</sup></xref> The new oral anticoagulants are, thus, the safest option for anticoagulation in elderly patients with higher risks of bleeding, patients with difficulties in adhering to INR monitoring, patients using multiple medications, or patients who individually opt for them. It is, nonetheless, necessary to adjust doses according to renal function and age (&lt; or &gt; 75)<xref ref-type="bibr" rid="B330"><sup>330</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B331"><sup>331</sup></xref> (grade of recommendation I, level of evidence B). Until recently, there were some concerns due to the lack of a specific antidote for reversing the anticoagulant effects of non-vitamin K antagonists; idarucizumab, however, has been introduced and was recently approved for use in humans in order to reverse the effects of dabigatran.<xref ref-type="bibr" rid="B332"><sup>332</sup></xref></p>
            <sec>
              <title>7.3.3.1. General Recommendations</title>
              <list list-type="order">
                <list-item>
                  <p>Unless there are formal contraindications to anticoagulation, elderly AF patients should begin anticoagulation, if their CHADS<sub>2</sub>VCAS<sub>2</sub> scores are &#8805; 2 for men and &#8805; 3 for women (grade of recommendation I, level of evidence A).<xref ref-type="bibr" rid="B324"><sup>324</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B325"><sup>325</sup></xref> If the CHADS<sub>2</sub>VCAS<sub>2</sub> score is &lt; 2 for men or &lt; 3 for women and LA size is &gt; 5.0 cm (or area indexed by body surface &gt; 30 mm/m<sup>2</sup>) on transthoracic echocardiography, anticoagulation should also be initiated (grade of recommendation IIa, level of evidence B). Elderly patients &lt; age 65, with CHADS<sub>2</sub>VCAS<sub>2</sub> = 0 for men or 1 for women should only start anticoagulation if LA &gt; 5.0 cm or in the presence of moderate to severe spontaneous contrast or thrombus on transesophageal echocardiography (grade of recommendation IIa, level of evidence B).</p>
                </list-item>
                <list-item>
                  <p>The HAS-BLED score is recommended to evaluate risk of bleeding during anticoagulation (grade of recommendation I, level of evidence B). Elderly patients are considered at higher risks if they are &gt; age 85, are fragile, have renal or hepatic insufficiency, have moderate to severe cognitive impairment, or have low levels of education, as well as during the first 90 days of treatment with anticoagulants. In these patients, anticoagulation is recommended with dose adjustment and more regular follow-up; however, it should not be contraindicated (grade of recommendation I, level of evidence C).</p>
                </list-item>
                <list-item>
                  <p>In parallel, the risk of hemorrhagic complications may further be reduced by controlling SAH and the risk of falls, as well as by paying attention to the introduction of new drugs in association with antiplatelet medications and antibiotics, which may interfere with serum levels or increase the risk of bleeding.</p>
                </list-item>
                <list-item>
                  <p>For warfarin patients, INR is recommended 5 to 7 days after beginning antibiotic therapy (grade of recommendation I, level of evidence C).</p>
                </list-item>
                <list-item>
                  <p>Regarding the choice of anticoagulant, current evidence demonstrates that direct oral anticoagulants (DOAC) are preferable to warfarin, except in patients with moderate to severe mitral stenosis and patients with valve prostheses (grade of recommendation I, level of evidence A).<xref ref-type="bibr" rid="B324"><sup>324</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B325"><sup>325</sup></xref> These Guidelines, however, also recommend warfarin use, in situations of availability or preference, owing to the fact that it is an oral drug that is well known, inexpensive, and widely available to patients through the public system in Brazil, as well as to the fact that it has an antagonist (vitamin K) available to reverse its anticoagulant effect (grade of recommendation I, level of evidence A).</p>
                </list-item>
                <list-item>
                  <p>DOAC are a safe option for anticoagulation in elderly patients with higher risks of bleeding, in patients with difficulties in adhering to INR monitoring, patients using multiple medications, or patients who individually opt for them. It is, nonetheless, necessary to adjust doses according to renal function and age<xref ref-type="bibr" rid="B330"><sup>330</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B331"><sup>331</sup></xref> (grade of recommendation I, level of evidence A). Rivaroxaban and edoxaban are the DOAC of choice given their use practicality (taken once a day). In patients with dyspepsia, dabigatran should be avoided (grade of recommendation I, level of evidence B). No DOAC have been tested with severe renal insufficiency.<xref ref-type="bibr" rid="B324"><sup>324</sup></xref> For this reason, these Guidelines do not recommend using them in patients with creatinine clearance &lt; 30 ml/min, in which case warfarin is preferable (grade of recommendation I, level of evidence B).</p>
                </list-item>
              </list>
              <table-wrap id="t88">
                <table frame="hsides" rules="groups">
                  <colgroup width="20%">
                    <col/>
                    <col/>
                    <col/>
                    <col/>
                    <col/>
                  </colgroup>
                  <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                    <tr>
                      <th align="left" valign="top" colspan="5">Recommended doses for elderly patients</th>
                    </tr>
                    <tr>
                      <th align="center" valign="top"/>
                      <th align="center" valign="top">Dabigatran</th>
                      <th align="center" valign="top">Rivaroxaban</th>
                      <th align="center" valign="top">Apixaban</th>
                      <th align="center" valign="top">Endoxaban</th>
                    </tr>
                  </thead>
                  <tbody style="border-bottom: thin solid; border-color: #000000">
                    <tr>
                      <td align="left" valign="top">Commercial presentation</td>
                      <td align="center" valign="top">150 mg 110 mg</td>
                      <td align="center" valign="top">20 mg 15 mg 10 mg</td>
                      <td align="center" valign="top">5 mg 2.5 mg</td>
                      <td align="center" valign="top">30 mg 60 mg</td>
                    </tr>
                    <tr>
                      <td align="left" valign="top" rowspan="2">Dose</td>
                      <td align="center" valign="top">150 mg CrCl &gt; 50 ml/min</td>
                      <td align="center" valign="top">20 mg CrCl &gt; 50 ml/min</td>
                      <td align="center" valign="top">5 mg CrCl &gt; 30 ml/min</td>
                      <td align="center" valign="top">60 mg CrCl &gt; 50 ml/min</td>
                    </tr>
                    <tr>
                      <td align="center" valign="top">110 mg CrCl between 30 and 50 ml/min</td>
                      <td align="center" valign="top">15 mg CrCl between 30 and 50 ml/min</td>
                      <td align="center" valign="top">2.5 mg CrCl 15-30 ml/min or Two of the following criteria: &#8805; 80 years old Weight &#8804; 60 kg Creatinine &#8805; 1.5 mg</td>
                      <td align="center" valign="top">30 mg CrCl 15-50 ml/min or weight &#8804; 60 kg</td>
                    </tr>
                    <tr>
                      <td align="left" valign="top">Posology</td>
                      <td align="center" valign="top">2 x day</td>
                      <td align="center" valign="top">1 x day</td>
                      <td align="center" valign="top">2 x day</td>
                      <td align="center" valign="top">1 x day</td>
                    </tr>
                    <tr>
                      <td align="left" valign="top" rowspan="2">Particularities</td>
                      <td align="center" valign="top">Dyspepsia is common</td>
                      <td align="center" valign="top">Higher risk of GI bleeding than warfarin</td>
                      <td align="center" valign="top"/>
                      <td align="center" valign="top"/>
                    </tr>
                    <tr>
                      <td align="center" valign="top">Avoid if CrCl &lt; 30 ml/min), recent stroke, and severe active hepatic disease</td>
                      <td align="center" valign="top">Avoid if CrCl &lt; 15 ml/min) and severe active hepatic disease</td>
                      <td align="center" valign="top">Avoid if CrCl &lt; 15 ml/min) or Creatinine &gt; 2.5 mg and severe active hepatic disease</td>
                      <td align="center" valign="top">Avoid if CrCl &lt; 15 ml/min or severe hepatic disease</td>
                    </tr>
                  </tbody>
                </table>
                <table-wrap-foot>
                  <fn id="TFN48a">
                    <p>
                      <italic>CrCl: creatinine clearance; GI: gastrointestinal. Source: European Heart Journal.</italic>
                      <xref ref-type="bibr" rid="B324">
                        <sup>324</sup>
                      </xref>
                    </p>
                  </fn>
                </table-wrap-foot>
              </table-wrap>
              <boxed-text>
                <p>
                  <bold>Erratum</bold>
                </p>
                <p>May 2019 Issue, vol. 112 (5), pages 649-705</p>
                <p>In the &#8220;Updated Geriatric Cardiology Guidelines of the Brazilian Society of Cardiology 2019&#8221;, with DOI: <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.5935/abc.20190086">https://doi.org/10.5935/abc.20190086</ext-link>, published in the journal Arquivos Brasileiros de Cardiologia, the name of the author Felipe Costa Fuchs was included on page 649, in the authors of chapter 6; on page 650, in the update authors; and on page 652, in the declaration of potential conflict of interest.</p>
              </boxed-text>
            </sec>
          </sec>
        </sec>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other" id="fn6">
          <p>
            <bold>Development:</bold>
          </p>
          <p>The Department of Geriatric Cardiology of the Brazilian Society of Cardiology (Departamento de Cardiogeriatria da Sociedade Brasileira da Cardiologia) and the Brazilian Geriatrics and Gerontology Society (Sociedade Brasileira de Geriatria e Gerontologia)</p>
        </fn>
        <fn fn-type="other" id="fn8">
          <p>
            <bold>Norms and Guidelines Council:</bold>
          </p>
          <p>Fernando Bacal, Leandro Ioschpe Zimerman, Paulo Ricardo Avancini Caramori, and Pedro A. Lemos</p>
        </fn>
        <fn fn-type="other" id="fn9">
          <p>
            <bold>Norms and Guidelines Coordinator:</bold>
          </p>
          <p>Ludhmila Abrah&#227;o Hajjar</p>
        </fn>
        <fn fn-type="other" id="fn10">
          <p>
            <bold>Editors:</bold>
          </p>
          <p>Gilson Soares Feitosa-Filho, Jos&#233; Maria Peixoto, Jos&#233; Elias Soares Pinheiro</p>
        </fn>
        <fn fn-type="other" id="fn11">
          <p>
            <bold>These updated should be cited as:</bold>
          </p>
          <p>Feitosa-Filho GS, Peixoto JM, Pinheiro JES, Afiune Neto A, Albuquerque ALT, Cattani AC et al. Updated Geriatric Cardiology Guidelines of the Brazilian Society of Cardiology &#8211; 2019. Arq Bras Cardiol. 2019; 112(5):649-705.</p>
        </fn>
        <fn fn-type="other" id="fn12">
          <p>
            <bold>Note:</bold>
          </p>
          <p>The purpose of these Guidelines is to inform. They do not substitute the clinical judgment of doctors who, in final analysis, must determine which treatments are appropriate for their patients.</p>
        </fn>
        <fn fn-type="other" id="fn13">
          <label>Erratum</label>
          <p>
            <bold>May 2019 Issue, vol. 112 (5), pages 649-705</bold>
          </p>
          <p>In the &#8220;Updated Geriatric Cardiology Guidelines of the Brazilian Society of Cardiology &#8211; 2019&#8221;, with DOI: <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.5935/abc.20190086">https://doi.org/10.5935/abc.20190086</ext-link>, published in the journal Arquivos Brasileiros de Cardiologia, the name of the author Felipe Costa Fuchs was included on page 649, in the authors of chapter 6; on page 650, in the update authors; and on page 652, in the declaration of potential conflict of interest.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
