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  <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">tB3Kj9vS9PgN6TwJd8pNCPw</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2026000404601</article-id>
      <article-id pub-id-type="other">04601</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20260223</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Diretrizes</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Diretriz sobre Ecocardiografia de Estresse &#8211; 2026</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-9291-1308</contrib-id>
          <name>
            <surname>Camarozano</surname>
            <given-names>Ana Cristina</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-4884-0223</contrib-id>
          <name>
            <surname>Spina</surname>
            <given-names>Salvador Vicente</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
          <xref ref-type="aff" rid="aff3">
            <sup>3</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-6737-4187</contrib-id>
          <name>
            <surname>Souza</surname>
            <given-names>Jos&#233; Roberto Matos</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">
            <sup>4</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-8809-8783</contrib-id>
          <name>
            <surname>Melo</surname>
            <given-names>Marcelo Dantas Tavares de</given-names>
          </name>
          <xref ref-type="aff" rid="aff5">
            <sup>5</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-9131-0439</contrib-id>
          <name>
            <surname>Frota</surname>
            <given-names>Daniela do Carmo Rassi</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">
            <sup>6</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-0711-7995</contrib-id>
          <name>
            <surname>Barberato</surname>
            <given-names>Silvio Henrique</given-names>
          </name>
          <xref ref-type="aff" rid="aff7">
            <sup>7</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-8760-2052</contrib-id>
          <name>
            <surname>Guimar&#227;es</surname>
            <given-names>Fabio Villa&#231;a</given-names>
            <suffix>Filho</suffix>
          </name>
          <xref ref-type="aff" rid="aff8">
            <sup>8</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-5115-8495</contrib-id>
          <name>
            <surname>Acquatella</surname>
            <given-names>Harry</given-names>
          </name>
          <xref ref-type="aff" rid="aff9">
            <sup>9</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gimenes</surname>
            <given-names>Vera M&#225;rcia Lopes</given-names>
          </name>
          <xref ref-type="aff" rid="aff10">
            <sup>10</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-5804-9075</contrib-id>
          <name>
            <surname>Lowenstein</surname>
            <given-names>Jorge Alfredo</given-names>
          </name>
          <xref ref-type="aff" rid="aff11">
            <sup>11</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-3862-7672</contrib-id>
          <name>
            <surname>Pignatelli</surname>
            <given-names>Ricardo H</given-names>
          </name>
          <xref ref-type="aff" rid="aff12">
            <sup>12</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2214-203X</contrib-id>
          <name>
            <surname>Castillo</surname>
            <given-names>Jos&#233; Maria Del</given-names>
          </name>
          <xref ref-type="aff" rid="aff13">
            <sup>13</sup>
          </xref>
          <xref ref-type="aff" rid="aff14">
            <sup>14</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-4325-0590</contrib-id>
          <name>
            <surname>Oliveira</surname>
            <given-names>Joselina Luiza Menezes</given-names>
          </name>
          <xref ref-type="aff" rid="aff15">
            <sup>15</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-6650-1292</contrib-id>
          <name>
            <surname>Abreu</surname>
            <given-names>Jos&#233; Sebasti&#227;o de</given-names>
          </name>
          <xref ref-type="aff" rid="aff16">
            <sup>16</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-1909-2753</contrib-id>
          <name>
            <surname>Pretto</surname>
            <given-names>Jos&#233; Luis de Castro e Silva</given-names>
          </name>
          <xref ref-type="aff" rid="aff17">
            <sup>17</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0009-0004-8772-7954</contrib-id>
          <name>
            <surname>Shehadeh</surname>
            <given-names>Issam</given-names>
          </name>
          <xref ref-type="aff" rid="aff18">
            <sup>18</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-7046-8707</contrib-id>
          <name>
            <surname>Felix</surname>
            <given-names>Alex dos Santos</given-names>
          </name>
          <xref ref-type="aff" rid="aff19">
            <sup>19</sup>
          </xref>
          <xref ref-type="aff" rid="aff20">
            <sup>20</sup>
          </xref>
          <xref ref-type="aff" rid="aff21">
            <sup>21</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Andrade</surname>
            <given-names>Mercedes Maldonado</given-names>
          </name>
          <xref ref-type="aff" rid="aff22">
            <sup>22</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-0439-9808</contrib-id>
          <name>
            <surname>Sousa</surname>
            <given-names>Ant&#244;nio Carlos Sobral</given-names>
          </name>
          <xref ref-type="aff" rid="aff15">
            <sup>15</sup>
          </xref>
          <xref ref-type="aff" rid="aff23">
            <sup>23</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2634-4632</contrib-id>
          <name>
            <surname>Otto</surname>
            <given-names>Maria Estef&#226;nia Bosco</given-names>
          </name>
          <xref ref-type="aff" rid="aff24">
            <sup>24</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-0056-4378</contrib-id>
          <name>
            <surname>Vilela</surname>
            <given-names>Andrea de Andrade</given-names>
          </name>
          <xref ref-type="aff" rid="aff22">
            <sup>22</sup>
          </xref>
          <xref ref-type="aff" rid="aff25">
            <sup>25</sup>
          </xref>
          <xref ref-type="aff" rid="aff26">
            <sup>26</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2864-8701</contrib-id>
          <name>
            <surname>Fajardo</surname>
            <given-names>Pedro Gutierrez</given-names>
          </name>
          <xref ref-type="aff" rid="aff27">
            <sup>27</sup>
          </xref>
          <xref ref-type="aff" rid="aff28">
            <sup>28</sup>
          </xref>
          <xref ref-type="aff" rid="aff29">
            <sup>29</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-5005-5005</contrib-id>
          <name>
            <surname>Baroncini</surname>
            <given-names>Liz Andr&#233;a Villela</given-names>
          </name>
          <xref ref-type="aff" rid="aff30">
            <sup>30</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Machado</surname>
            <given-names>Cristiano Vieira</given-names>
          </name>
          <xref ref-type="aff" rid="aff31">
            <sup>31</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0009-0006-1768-3380</contrib-id>
          <name>
            <surname>Moreira</surname>
            <given-names>F&#225;bio Ca&#241;ellas</given-names>
          </name>
          <xref ref-type="aff" rid="aff32">
            <sup>32</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-4018-7346</contrib-id>
          <name>
            <surname>Hern&#225;ndez</surname>
            <given-names>Jos&#233; Mar&#237;a Hern&#225;ndez</given-names>
          </name>
          <xref ref-type="aff" rid="aff33">
            <sup>33</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-0794-7339</contrib-id>
          <name>
            <surname>Alves</surname>
            <given-names>Marco Stephan Lofrano</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-5531-9647</contrib-id>
          <name>
            <surname>Morhy</surname>
            <given-names>Samira Saady</given-names>
          </name>
          <xref ref-type="aff" rid="aff25">
            <sup>25</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-6110-2500</contrib-id>
          <name>
            <surname>Lima</surname>
            <given-names>M&#225;rcio Silva Miguel</given-names>
          </name>
          <xref ref-type="aff" rid="aff34">
            <sup>34</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-9083-8269</contrib-id>
          <name>
            <surname>Aguiar</surname>
            <given-names>Miguel Osman Dias</given-names>
          </name>
          <xref ref-type="aff" rid="aff35">
            <sup>35</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-0201-6754</contrib-id>
          <name>
            <surname>Mathias</surname>
            <given-names>Wilson</given-names>
            <suffix>Junior</suffix>
          </name>
          <xref ref-type="aff" rid="aff34">
            <sup>34</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-4551-1096</contrib-id>
          <name>
            <surname>Rocha</surname>
            <given-names>Let&#237;cia dos Santos de Oliveira</given-names>
          </name>
          <xref ref-type="aff" rid="aff36">
            <sup>36</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2462-2010</contrib-id>
          <name>
            <surname>Sbano</surname>
            <given-names>Jo&#227;o C&#233;sar Nunes</given-names>
          </name>
          <xref ref-type="aff" rid="aff34">
            <sup>34</sup>
          </xref>
          <xref ref-type="aff" rid="aff37">
            <sup>37</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-5611-4002</contrib-id>
          <name>
            <surname>Vrandecic</surname>
            <given-names>Barbara Athayde Linhares Martins</given-names>
          </name>
          <xref ref-type="aff" rid="aff38">
            <sup>38</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-1254-6820</contrib-id>
          <name>
            <surname>Roston</surname>
            <given-names>Fabio</given-names>
          </name>
          <xref ref-type="aff" rid="aff39">
            <sup>39</sup>
          </xref>
          <xref ref-type="aff" rid="aff40">
            <sup>40</sup>
          </xref>
          <xref ref-type="aff" rid="aff41">
            <sup>41</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2959-1874</contrib-id>
          <name>
            <surname>Rabischoffsky</surname>
            <given-names>Arnaldo</given-names>
          </name>
          <xref ref-type="aff" rid="aff42">
            <sup>42</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0009-0000-1656-6218</contrib-id>
          <name>
            <surname>Rolim</surname>
            <given-names>Juliana Paix&#227;o Etto</given-names>
          </name>
          <xref ref-type="aff" rid="aff34">
            <sup>34</sup>
          </xref>
          <xref ref-type="aff" rid="aff43">
            <sup>43</sup>
          </xref>
          <xref ref-type="aff" rid="aff44">
            <sup>44</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-9580-4703</contrib-id>
          <name>
            <surname>Silva</surname>
            <given-names>Raphael Aparecido Barreto da</given-names>
          </name>
          <xref ref-type="aff" rid="aff8">
            <sup>8</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-5861-1718</contrib-id>
          <name>
            <surname>Rossi</surname>
            <given-names>Guilherme de</given-names>
          </name>
          <xref ref-type="aff" rid="aff45">
            <sup>45</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0009-0003-4528-4174</contrib-id>
          <name>
            <surname>Staszko</surname>
            <given-names>Kamila Fernanda</given-names>
          </name>
          <xref ref-type="aff" rid="aff46">
            <sup>46</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-3388-5840</contrib-id>
          <name>
            <surname>Britt</surname>
            <given-names>Jolie</given-names>
          </name>
          <xref ref-type="aff" rid="aff47">
            <sup>47</sup>
          </xref>
          <xref ref-type="aff" rid="aff48">
            <sup>48</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Vieira</surname>
            <given-names>Marcelo Luiz Campos</given-names>
          </name>
          <xref ref-type="aff" rid="aff25">
            <sup>25</sup>
          </xref>
          <xref ref-type="aff" rid="aff34">
            <sup>34</sup>
          </xref>
          <xref ref-type="aff" rid="aff49">
            <sup>49</sup>
          </xref>
        </contrib>
        <aff id="aff1">
          <label>1</label>
          <institution content-type="orgname">Universidade Federal 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">Universidade Federal do Paran&#225;, Curitiba, PR &#8211; Brasil</institution>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution content-type="orgname">Hospital Aeron&#225;utico Central</institution>
          <addr-line>
            <named-content content-type="city">Buenos Aires</named-content>
            <named-content content-type="state">BA</named-content>
          </addr-line>
          <country country="AR">Argentina</country>
          <institution content-type="original">Hospital Aeron&#225;utico Central, Buenos Aires, BA &#8211; Argentina</institution>
        </aff>
        <aff id="aff3">
          <label>3</label>
          <institution content-type="orgname">Centro M&#233;dico Don Bosco</institution>
          <addr-line>
            <named-content content-type="city">Ramos Mej&#237;a Pcia</named-content>
            <named-content content-type="state">BA</named-content>
          </addr-line>
          <country country="AR">Argentina</country>
          <institution content-type="original">Centro M&#233;dico Don Bosco, Ramos Mej&#237;a Pcia, BA &#8211; Argentina</institution>
        </aff>
        <aff id="aff4">
          <label>4</label>
          <institution content-type="orgname">Universidade de Campinas</institution>
          <addr-line>
            <named-content content-type="city">Campinas</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade de Campinas, Campinas, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff5">
          <label>5</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, Jo&#227;o Pessoa, PB &#8211; Brasil</institution>
        </aff>
        <aff id="aff6">
          <label>6</label>
          <institution content-type="orgname">Hospital das Clinicas da 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">Hospital das Clinicas da Universidade Federal de Goi&#225;s, Goi&#226;nia, GO &#8211; Brasil</institution>
        </aff>
        <aff id="aff7">
          <label>7</label>
          <institution content-type="orgname">Pontif&#237;cia 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;, Curitiba, PR &#8211; Brasil</institution>
        </aff>
        <aff id="aff8">
          <label>8</label>
          <institution content-type="orgname">Instituto do Cora&#231;&#227;o de Mar&#237;lia</institution>
          <addr-line>
            <named-content content-type="city">Marilia</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 de Mar&#237;lia, Marilia, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff9">
          <label>9</label>
          <institution content-type="orgname">Centro Medico de Caracas</institution>
          <addr-line>
            <named-content content-type="city">Caracas</named-content>
            <named-content content-type="state">CCS</named-content>
          </addr-line>
          <country country="VE">Venezuela</country>
          <institution content-type="original">Centro Medico de Caracas, Caracas, CCS &#8211; Venezuela</institution>
        </aff>
        <aff id="aff10">
          <label>10</label>
          <institution content-type="orgname">Hospital 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">Hospital do Cora&#231;&#227;o, S&#227;o Paulo, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff11">
          <label>11</label>
          <institution content-type="orgname">Investigaciones Medicas Buenos Aires</institution>
          <addr-line>
            <named-content content-type="city">Buenos Aires</named-content>
            <named-content content-type="state">BA</named-content>
          </addr-line>
          <country country="AR">Argentina</country>
          <institution content-type="original">Cardiodiagn&#243;stico, Investigaciones Medicas Buenos Aires, Buenos Aires, BA &#8211; Argentina</institution>
        </aff>
        <aff id="aff12">
          <label>12</label>
          <institution content-type="orgname">Texas Children's Hospital- Baylor College of Medicine</institution>
          <addr-line>
            <named-content content-type="city">Houston</named-content>
            <named-content content-type="state">TX</named-content>
          </addr-line>
          <country country="US">Estados Unidos da Am&#233;rica</country>
          <institution content-type="original">Texas Children's Hospital- Baylor College of Medicine, Houston, TX &#8211; Estados Unidos da Am&#233;rica</institution>
        </aff>
        <aff id="aff13">
          <label>13</label>
          <institution content-type="orgname">Escola de Ecografia 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">Escola de Ecografia de Pernambuco, Recife, PE &#8211; Brasil</institution>
        </aff>
        <aff id="aff14">
          <label>14</label>
          <institution content-type="orgname">Universidade Cat&#243;lica 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 Cat&#243;lica de Pernambuco, Recife, PE &#8211; Brasil</institution>
        </aff>
        <aff id="aff15">
          <label>15</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, Aracaju, SE &#8211; Brasil</institution>
        </aff>
        <aff id="aff16">
          <label>16</label>
          <institution content-type="orgname">Clinicardio de Fortaleza e Cardioexata</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">Clinicardio de Fortaleza e Cardioexata, Fortaleza, CE &#8211; Brasil</institution>
        </aff>
        <aff id="aff17">
          <label>17</label>
          <institution content-type="orgname">Hospital S&#227;o Vicente de Paulo</institution>
          <addr-line>
            <named-content content-type="city">Passo Fundo</named-content>
            <named-content content-type="state">RS</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Hospital S&#227;o Vicente de Paulo, Passo Fundo, RS &#8211; Brasil</institution>
        </aff>
        <aff id="aff18">
          <label>18</label>
          <institution content-type="orgname">Cl&#237;nica Cardiovision</institution>
          <addr-line>
            <named-content content-type="city">Esteio</named-content>
            <named-content content-type="state">RS</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Cl&#237;nica Cardiovision, Esteio, RS &#8211; Brasil</institution>
        </aff>
        <aff id="aff19">
          <label>19</label>
          <institution content-type="orgname">Instituto Nacional de Cardiologia</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">Instituto Nacional de Cardiologia, Rio de Janeiro, RJ &#8211; Brasil</institution>
        </aff>
        <aff id="aff20">
          <label>20</label>
          <institution content-type="orgname">Diagn&#243;sticos da Am&#233;rica S.A. (DASA-RJ)</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">Diagn&#243;sticos da Am&#233;rica S.A. (DASA-RJ), Rio de Janeiro, RJ &#8211; Brasil</institution>
        </aff>
        <aff id="aff21">
          <label>21</label>
          <institution content-type="orgname">Complexo Hospitalar Americas</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">Complexo Hospitalar Americas, Rio de Janeiro, RJ &#8211; Brasil</institution>
        </aff>
        <aff id="aff22">
          <label>22</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="aff23">
          <label>23</label>
          <institution content-type="orgname">Hospital S&#227;o Lucas</institution>
          <institution content-type="orgdiv1">Rede D'Or de Aracaju</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, Rede D'Or de Aracaju, Aracaju, SE &#8211; Brasil</institution>
        </aff>
        <aff id="aff24">
          <label>24</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, Bras&#237;lia, DF &#8211; Brasil</institution>
        </aff>
        <aff id="aff25">
          <label>25</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="aff26">
          <label>26</label>
          <institution content-type="orgname">Hospital Lefort Morumbi</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 Lefort Morumbi, S&#227;o Paulo, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff27">
          <label>27</label>
          <institution content-type="orgname">Hospital de Especialidades San Francisco de Asis</institution>
          <addr-line>
            <named-content content-type="city">Guadalajara</named-content>
            <named-content content-type="state">JAL</named-content>
          </addr-line>
          <country country="MX">M&#233;xico</country>
          <institution content-type="original">Hospital de Especialidades San Francisco de Asis, Guadalajara, JAL &#8211; M&#233;xico</institution>
        </aff>
        <aff id="aff28">
          <label>28</label>
          <institution content-type="orgname">Cardiotest</institution>
          <addr-line>
            <named-content content-type="city">Guadalajara</named-content>
            <named-content content-type="state">JAL</named-content>
          </addr-line>
          <country country="MX">M&#233;xico</country>
          <institution content-type="original">Cardiotest, Guadalajara, JAL &#8211; M&#233;xico</institution>
        </aff>
        <aff id="aff29">
          <label>29</label>
          <institution content-type="orgname">Laboratorio de Ecocaerdiografia</institution>
          <addr-line>
            <named-content content-type="city">Guadalajara</named-content>
            <named-content content-type="state">JAL</named-content>
          </addr-line>
          <country country="MX">M&#233;xico</country>
          <institution content-type="original">Laboratorio de Ecocaerdiografia, Guadalajara, JAL &#8211; M&#233;xico</institution>
        </aff>
        <aff id="aff30">
          <label>30</label>
          <institution content-type="orgname">Hospital Nossa Senhora Das Gracas</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">Hospital Nossa Senhora Das Gracas, Curitiba, PR &#8211; Brasil</institution>
        </aff>
        <aff id="aff31">
          <label>31</label>
          <institution content-type="orgname">Fleury Medicina e Sa&#250;de</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">Fleury Medicina e Sa&#250;de, Grupo Fleury, S&#227;o Paulo, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff32">
          <label>32</label>
          <institution content-type="orgname">Santa Casa De Miseric&#243;rdia De Porto Alegre</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">Santa Casa De Miseric&#243;rdia De Porto Alegre, Porto Alegre, RS &#8211; Brasil</institution>
        </aff>
        <aff id="aff33">
          <label>33</label>
          <institution content-type="orgname">Imaging Cardiac Department. Doctors Hospital Auna</institution>
          <addr-line>
            <named-content content-type="city">Monterrey</named-content>
            <named-content content-type="state">NL</named-content>
          </addr-line>
          <country country="MX">M&#233;xico.</country>
          <institution content-type="original">Imaging Cardiac Department. Doctors Hospital Auna, Monterrey, NL &#8211; M&#233;xico.</institution>
        </aff>
        <aff id="aff34">
          <label>34</label>
          <institution content-type="orgname">Instituto Do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da Faculdade de Medicina da 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">Instituto Do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff35">
          <label>35</label>
          <institution content-type="orgname">Hospital Benefic&#234;ncia Portuguesa 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">Hospital Benefic&#234;ncia Portuguesa de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff36">
          <label>36</label>
          <institution content-type="orgname">Hospital Pequeno Pr&#237;ncipe</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">Hospital Pequeno Pr&#237;ncipe, Curitiba, PR &#8211; Brasil</institution>
        </aff>
        <aff id="aff37">
          <label>37</label>
          <institution content-type="orgname">Grupo Fleury Medicina e Sa&#250;de</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">Grupo Fleury Medicina e Sa&#250;de, S&#227;o Paulo, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff38">
          <label>38</label>
          <institution content-type="orgname">Hospital Biocor/Rede D'or</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 Biocor/Rede D'or, Belo Horizonte, MG &#8211; Brasil</institution>
        </aff>
        <aff id="aff39">
          <label>39</label>
          <institution content-type="orgname">Cl&#237;nica Clinicardio</institution>
          <addr-line>
            <named-content content-type="city">Londrina</named-content>
            <named-content content-type="state">PR</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Cl&#237;nica Clinicardio, Londrina, PR &#8211; Brasil</institution>
        </aff>
        <aff id="aff40">
          <label>40</label>
          <institution content-type="orgname">Hospital Norte Paranaense HONPAR</institution>
          <addr-line>
            <named-content content-type="city">Arapongas</named-content>
            <named-content content-type="state">PR</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Hospital Norte Paranaense HONPAR, Arapongas, PR &#8211; Brasil</institution>
        </aff>
        <aff id="aff41">
          <label>41</label>
          <institution content-type="orgname">Grupo Cura (Labimagem e Ultramed)</institution>
          <addr-line>
            <named-content content-type="city">Londrina</named-content>
            <named-content content-type="state">PR</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Grupo Cura (Labimagem e Ultramed), Londrina, PR &#8211; Brasil</institution>
        </aff>
        <aff id="aff42">
          <label>42</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="aff43">
          <label>43</label>
          <institution content-type="orgname">Hospital S&#237;rio Liban&#234;</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 S&#237;rio Liban&#234;, S&#227;o Paulo, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff44">
          <label>44</label>
          <institution content-type="orgname">Alta (Rede Dasa)</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">Alta (Rede Dasa), S&#227;o Paulo, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff45">
          <label>45</label>
          <institution content-type="orgname">Centro Especializado em Cardiologia LTDA</institution>
          <addr-line>
            <named-content content-type="city">Campinas</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Centro Especializado em Cardiologia LTDA, Campinas, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff46">
          <label>46</label>
          <institution content-type="orgname">Complexo do Hospital de Cl&#237;nicas da Universidade Federal do Paran&#225; (CHC-UFPR)</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">Complexo do Hospital de Cl&#237;nicas da Universidade Federal do Paran&#225; (CHC-UFPR), Curitiba, PR &#8211; Brasil</institution>
        </aff>
        <aff id="aff47">
          <label>47</label>
          <institution content-type="orgname">Baylor College of Medicine</institution>
          <addr-line>
            <named-content content-type="city">Houston</named-content>
            <named-content content-type="state">TX</named-content>
          </addr-line>
          <country country="US">Estados Unidos da Am&#233;rica</country>
          <institution content-type="original">Baylor College of Medicine, Houston, TX &#8211; Estados Unidos da Am&#233;rica</institution>
        </aff>
        <aff id="aff48">
          <label>48</label>
          <institution content-type="orgname">Texas Children's Hospital</institution>
          <addr-line>
            <named-content content-type="city">Houston</named-content>
            <named-content content-type="state">TX</named-content>
          </addr-line>
          <country country="US">Estados Unidos da Am&#233;rica</country>
          <institution content-type="original">Texas Children's Hospital, Houston, TX &#8211; Estados Unidos da Am&#233;rica</institution>
        </aff>
        <aff id="aff49">
          <label>49</label>
          <institution content-type="orgname">Faculdade de Medicina da 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">Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brasil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><label>Correspond&#234;ncia:</label> 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>diretrizes@cardiol.br</email></corresp>
        <fn fn-type="edited-by">
          <label>Editor Coordenador:</label>
          <p>Ana Cristina Camarozano</p>
        </fn>
        <fn fn-type="edited-by">
          <label>Editor Respons&#225;vel pela Revis&#227;o:</label>
          <p>Humberto Graner Moreira.</p>
        </fn>
        <fn fn-type="edited-by">
          <label>Coeditores:</label>
          <p>Salvador Spina, Jos&#233; Roberto Mattos de Souza, Marcelo Dantas Tavares de Melo, Daniela do Carmo Rassi Frota, Silvio Henrique Barberato, Marcelo Luiz Campos Vieira</p>
        </fn>
      </author-notes>
      <pub-date publication-format="electronic" date-type="pub">
        <day>15</day>
        <month>06</month>
        <year>2026</year>
      </pub-date>
      <pub-date publication-format="electronic" date-type="collection">
        <year>2026</year>
      </pub-date>
      <volume>123</volume>
      <issue>4</issue>
      <elocation-id>e20260223</elocation-id>
      <permissions>
        <license license-type="open-access" xml:lang="en" xlink:href="https://creativecommons.org/licenses/by/4.0/">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License</license-p>
        </license>
      </permissions>
      <counts>
        <fig-count count="74"/>
        <table-count count="64"/>
        <equation-count count="0"/>
        <ref-count count="363"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <table-wrap id="t1">
      <table frame="hsides" rules="rows">
        <colgroup width="50%">
          <col/>
          <col/>
        </colgroup>
        <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
          <tr>
            <th align="center" valign="middle" colspan="2">Diretriz sobre Ecocardiografia de Estresse &#8211; 2026</th>
          </tr>
          <tr>
            <th align="center" valign="middle" colspan="2">O relat&#243;rio abaixo lista as declara&#231;&#245;es de interesse conforme relatadas &#224; SBC pelos especialistas durante o per&#237;odo de desenvolvimento deste posicionamento, 2025/2026.</th>
          </tr>
          <tr>
            <th align="left" valign="middle">Especialista</th>
            <th align="center" valign="middle">Tipo de relacionamento com a ind&#250;stria</th>
          </tr>
        </thead>
        <tbody style="border-bottom: thin solid; border-color: #000000">
          <tr>
            <td align="left" valign="middle">Alex dos Santos Felix</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Ana Cristina Camarozano</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Andrea de Andrade Vilela</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Ant&#244;nio Carlos Sobral Sousa</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Arnaldo Rabischoffsky</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Barbara Athayde Linhares Martins Vrandecic</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Cristiano Vieira Machado</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Daniela do Carmo Rassi Frota</td>
            <td align="left" valign="middle">Declara&#231;&#227;o financeira<break/> A - Pagamento de qualquer esp&#233;cie e desde que economicamente apreci&#225;veis, feitos a (i) voc&#234;, (ii) ao seu c&#244;njuge/ companheiro ou a qualquer outro membro que resida com voc&#234;, (iii) a qualquer pessoa jur&#237;dica em que qualquer destes seja controlador, s&#243;cio, acionista ou participante, de forma direta ou indireta, recebimento por palestras, aulas, atua&#231;&#227;o como proctor de treinamentos, remunera&#231;&#245;es, honor&#225;rios pagos por participa&#231;&#245;es em conselhos consultivos, de investigadores, ou outros comit&#234;s, etc. Provenientes da ind&#250;stria farmac&#234;utica, de &#243;rteses, pr&#243;teses, equipamentos e implantes, brasileiras ou estrangeiras:<break/> - AstraZeneca do Brasil Ltda: Forxiga.</td>
          </tr>
          <tr>
            <td align="left" valign="middle">F&#225;bio Ca&#241;ellas Moreira</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Fabio Roston</td>
            <td align="left" valign="middle">Declara&#231;&#227;o financeira<break/> A - Pagamento de qualquer esp&#233;cie e desde que economicamente apreci&#225;veis, feitos a (i) voc&#234;, (ii) ao seu c&#244;njuge/ companheiro ou a qualquer outro membro que resida com voc&#234;, (iii) a qualquer pessoa jur&#237;dica em que qualquer destes seja controlador, s&#243;cio, acionista ou participante, de forma direta ou indireta, recebimento por palestras, aulas, atua&#231;&#227;o como proctor de treinamentos, remunera&#231;&#245;es, honor&#225;rios pagos por participa&#231;&#245;es em conselhos consultivos, de investigadores, ou outros comit&#234;s, etc. Provenientes da ind&#250;stria farmac&#234;utica, de &#243;rteses, pr&#243;teses, equipamentos e implantes, brasileiras ou estrangeiras:<break/> - Boston scientific: Proctoria de oclus&#227;o de ap&#234;ndice atrial esquerdo.</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Fabio Villaca Guimar&#227;es filho</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Guilherme De Rossi</td>
            <td align="left" valign="middle">Outros relacionamentos <break/>Participa&#231;&#227;o societ&#225;ria de qualquer natureza e qualquer valor economicamente apreci&#225;vel de empresas na &#225;rea de sa&#250;de, de ensino ou em empresas concorrentes ou fornecedoras da SBC:<break/> - &#193;rea da Sa&#250;de</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Harry Acquatella</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Issam Shehadeh</td>
            <td align="left" valign="middle">Declara&#231;&#227;o financeira<break/> A - Pagamento de qualquer esp&#233;cie e desde que economicamente apreci&#225;veis, feitos a (i) voc&#234;, (ii) ao seu c&#244;njuge/ companheiro ou a qualquer outro membro que resida com voc&#234;, (iii) a qualquer pessoa jur&#237;dica em que qualquer destes seja controlador, s&#243;cio, acionista ou participante, de forma direta ou indireta, recebimento por palestras, aulas, atua&#231;&#227;o como proctor de treinamentos, remunera&#231;&#245;es, honor&#225;rios pagos por participa&#231;&#245;es em conselhos consultivos, de investigadores, ou outros comit&#234;s, etc. Provenientes da ind&#250;stria farmac&#234;utica, de &#243;rteses, pr&#243;teses, equipamentos e implantes, brasileiras ou estrangeiras:<break/> - GE Healthcare: Handson Ecocardiografia de Estresse.<break/> Outros relacionamentos <break/>Financiamento de atividades de educa&#231;&#227;o m&#233;dica continuada, incluindo viagens, hospedagens e inscri&#231;&#245;es para congressos e cursos, provenientes da ind&#250;stria farmac&#234;utica, de &#243;rteses, pr&#243;teses, equipamentos e implantes, brasileiras ou estrangeiras:<break/> - Torrent: Cardiologia; Medley Sanofi : Zinpass Eze.</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Jo&#227;o Cesar Nunes Sbano</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Jolie Britt</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Jorge Alfredo Lowenstein</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Jos&#233; Luis de Castro e Silva Pretto</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Jos&#233; Maria Del Castillo</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Jos&#233; Mar&#237;a Hern&#225;ndez Hern&#225;ndez</td>
            <td align="left" valign="middle">Outros relacionamentos <break/>Financiamento de atividades de educa&#231;&#227;o m&#233;dica continuada, incluindo viagens, hospedagens e inscri&#231;&#245;es para congressos e cursos, provenientes da ind&#250;stria farmac&#234;utica, de &#243;rteses, pr&#243;teses, equipamentos e implantes, brasileiras ou estrangeiras:<break/> - Vitalmex: LVAD &#8211; Vitacor..<break/> V&#237;nculo empregat&#237;cio com a ind&#250;stria farmac&#234;utica, de &#243;rteses, pr&#243;teses, equipamentos e implantes, brasileiras ou estrangeiras, assim como se tem rela&#231;&#227;o v&#237;nculo empregat&#237;cio com operadoras de planos de sa&#250;de ou em auditorias m&#233;dicas (incluindo meio per&#237;odo) durante o ano para o qual voc&#234; est&#225; declarando:<break/> - Vitalmex: LVAD &#8211; Vitacor.</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Jos&#233; Roberto Matos Souza</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Jos&#233; Sebasti&#227;o de Abreu</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Joselina Luzia Menezes Oliveira</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Juliana Paix&#227;o Etto Rolim</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Kamila Fernanda Staszko</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Let&#237;cia dos Santos de Oliveira Rocha</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Liz Andr&#233;a Villela Baroncini</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Marcelo dantas tavares de melo</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Marcelo Luiz Campos Vieira</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">M&#225;rcio Silva Miguel Lima</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Marco Stephan Lofrano Alves</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Maria Estef&#226;nia Bosco Otto</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Mercedes Maldonado Andrade</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Miguel Osman Dias Aguiar</td>
            <td align="left" valign="middle">Outros relacionamentos <break/>Participa&#231;&#227;o societ&#225;ria de qualquer natureza e qualquer valor economicamente apreci&#225;vel de empresas na &#225;rea de sa&#250;de, de ensino ou em empresas concorrentes ou fornecedoras da SBC:<break/> - &#193;rea da Sa&#250;de</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Pedro Gutierrez-Fajardo</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Raphael Aparecido Barreto da Silva</td>
            <td align="left" valign="middle">Declara&#231;&#227;o financeira<break/> B - Financiamento de pesquisas sob sua responsabilidade direta/pessoal (direcionado ao departamento ou institui&#231;&#227;o) provenientes da ind&#250;stria farmac&#234;utica, de &#243;rteses, pr&#243;teses, equipamentos e implantes, brasileiras ou estrangeiras:<break/> - Lilly: obesidade, lipoprote&#237;na(a); Amgen: insufici&#234;ncia card&#237;aca, lipoprote&#237;na(a), doen&#231;a arterial coronariana; Sanofi: fibrila&#231;&#227;o atrial; Vertex: insufici&#234;ncia renal; Boehringer: insufici&#234;ncia card&#237;aca; AstraZeneca: dislipidemia.</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Ricardo H Pignatelli</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Salvador Vicente Spina</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Samira Saady Morhy</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Silvio Henrique Barberato</td>
            <td align="left" valign="middle">Declara&#231;&#227;o financeira<break/> A - Pagamento de qualquer esp&#233;cie e desde que economicamente apreci&#225;veis, feitos a (i) voc&#234;, (ii) ao seu c&#244;njuge/ companheiro ou a qualquer outro membro que resida com voc&#234;, (iii) a qualquer pessoa jur&#237;dica em que qualquer destes seja controlador, s&#243;cio, acionista ou participante, de forma direta ou indireta, recebimento por palestras, aulas, atua&#231;&#227;o como proctor de treinamentos, remunera&#231;&#245;es, honor&#225;rios pagos por participa&#231;&#245;es em conselhos consultivos, de investigadores, ou outros comit&#234;s, etc. Provenientes da ind&#250;stria farmac&#234;utica, de &#243;rteses, pr&#243;teses, equipamentos e implantes, brasileiras ou estrangeiras:<break/> - Pfizer: Amiloidose; AstraZeneca: ICFEP.<break/> Outros relacionamentos <break/>Financiamento de atividades de educa&#231;&#227;o m&#233;dica continuada, incluindo viagens, hospedagens e inscri&#231;&#245;es para congressos e cursos, provenientes da ind&#250;stria farmac&#234;utica, de &#243;rteses, pr&#243;teses, equipamentos e implantes, brasileiras ou estrangeiras:<break/> - Pfizer: Amiloidose.</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Vera Marcia Lopes Gimenes</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
          <tr>
            <td align="left" valign="middle">Wilson Mathias Junior</td>
            <td align="left" valign="middle">Nada a ser declarado</td>
          </tr>
        </tbody>
      </table>
    </table-wrap>
    <sec>
      <title>Sum&#225;rio</title>
      <list list-type="simple">
        <list-item>
          <p><bold>1. O Papel da Ecocardiografia de Repouso Realizada no Momento da Ecocardiografia de Estresse F&#237;sico ou Farmacol&#243;gico</bold> 9</p>
        </list-item>
        <list-item>
          <p><bold>2. A Evolu&#231;&#227;o da Ecocardiografia de Estresse: do Princ&#237;pio aos Dias de Hoje</bold> 9</p>
        </list-item>
        <list-item>
          <p><bold>3. M&#233;todos Provocativos de Isquemia</bold> 9</p>
          <list list-type="simple">
            <list-item>
              <p><bold>3.1. Ecocardiografia de Estresse com Exerc&#237;cio (Bicicleta, Esteira Ergom&#233;trica ou Ciclomaca)</bold> 10</p>
            </list-item>
            <list-item>
              <p><bold>3.2 Ecocardiografia de Estresse Farmacol&#243;gico</bold> 10</p>
            </list-item>
            <list-item>
              <p><bold>3.3. Ecocardiografia de Estresse no Espasmo Coron&#225;rio</bold> 10</p>
            </list-item>
            <list-item>
              <p><bold>3.4. Ecocardiografia de Estresse com Marca-Passo</bold> 11</p>
            </list-item>
          </list>
        </list-item>
        <list-item>
          <p><bold>4. Ecocardiografia de Estresse F&#237;sico (Esteira, Bicicleta e Ciclomaca)</bold> 11</p>
        </list-item>
        <list-item>
          <p><bold>5. Ecocardiografia de Estresse com Dobutamina na Avalia&#231;&#227;o de Isquemia Mioc&#225;rdica</bold> 13</p>
          <list list-type="simple">
            <list-item>
              <p><bold>5.1. Protocolo da Ecocardiografia de Estresse Farmacol&#243;gico com Dobutamina</bold> 13</p>
            </list-item>
            <list-item>
              <p><bold>5.2. Tipo de Resposta Mioc&#225;rdica</bold> 16</p>
            </list-item>
            <list-item>
              <p><bold>5.3. Avalia&#231;&#227;o Durante a Ecocardiografia de Estresse Farmacol&#243;gico com Dobutamina e na Recupera&#231;&#227;o</bold> 18</p>
            </list-item>
            <list-item>
              <p><bold>5.4. Dilata&#231;&#227;o Isqu&#234;mica Transit&#243;ria do Ventr&#237;culo Esquerdo</bold> 18</p>
            </list-item>
            <list-item>
              <p><bold>5.5. Compara&#231;&#227;o com Outras Modalidades de Imagem</bold> 19</p>
            </list-item>
            <list-item>
              <p><bold>5.6. Valor da Ecocardiografia de Estresse Farmacol&#243;gico com Dobutamina Negativa</bold> 19</p>
            </list-item>
            <list-item>
              <p><bold>5.7. Complica&#231;&#245;es da Ecocardiografia de Estresse Farmacol&#243;gico com Dobutamina</bold> 19</p>
            </list-item>
          </list>
        </list-item>
        <list-item>
          <p><bold>6. Ecocardiografia de Estresse com Dipiridamol</bold> 20</p>
          <list list-type="simple">
            <list-item>
              <p><bold>6.1. Protocolos</bold> 20</p>
            </list-item>
            <list-item>
              <p><bold>6.2. Efeitos Colaterais</bold> 21</p>
            </list-item>
            <list-item>
              <p><bold>6.3. Contraindica&#231;&#245;es</bold> 21</p>
            </list-item>
            <list-item>
              <p><bold>6.4. Reserva de Fluxo Coronariano</bold> 21</p>
            </list-item>
            <list-item>
              <p><bold>6.5. Acur&#225;cia</bold> 21</p>
            </list-item>
          </list>
        </list-item>
        <list-item>
          <p><bold>7. Ecocardiografia de Estresse com Adenosina ou Regadenoson</bold> 22</p>
          <list list-type="simple">
            <list-item>
              <p><bold>7.1. Uso Durante a Ecocardiografia de Estresse</bold> 23</p>
              <list list-type="simple">
                <list-item>
                  <p><bold>7.1.1. Indica&#231;&#245;es</bold> 23</p>
                </list-item>
              </list>
            </list-item>
            <list-item>
              <p><bold>7.2. Protocolo para Ecocardiografia de Estresse com Adenosina</bold> 24</p>
            </list-item>
            <list-item>
              <p><bold>7.3. Protocolo para Ecocardiografia de Estresse com Regadenoson</bold> 24</p>
            </list-item>
            <list-item>
              <p><bold>7.4 Contraindica&#231;&#245;es</bold> 24</p>
            </list-item>
            <list-item>
              <p><bold>7.5. Efeitos Colaterais</bold> 24</p>
            </list-item>
            <list-item>
              <p><bold>7.6. Acur&#225;cia Diagn&#243;stica</bold> 24</p>
            </list-item>
          </list>
        </list-item>
        <list-item>
          <p><bold>8. Outras Modalidades de Ecocardiografia de Estresse: Marca-Passo, Ergonovina, <italic>Handgrip</italic> e Hiperventila&#231;&#227;o</bold> 24</p>
          <list list-type="simple">
            <list-item>
              <p><bold>8.1. Ecocardiografia de Estresse por Marca-Passo</bold> 24</p>
            </list-item>
            <list-item>
              <p><bold>8.2. Associa&#231;&#227;o do <italic>Handgrip</italic> &#224; Ecocardiografia de Estresse</bold> 25</p>
            </list-item>
            <list-item>
              <p><bold>8.3. Ecocardiografia de Estresse com Ergonovina e Hiperventila&#231;&#227;o</bold> 25</p>
            </list-item>
          </list>
        </list-item>
        <list-item>
          <p><bold>9. Ecocardiografia de Estresse Diast&#243;lico</bold> 25</p>
          <list list-type="simple">
            <list-item>
              <p><bold>9.1. Resposta Normal e Anormal ao Exerc&#237;cio na Fun&#231;&#227;o Diast&#243;lica</bold> 25</p>
            </list-item>
            <list-item>
              <p><bold>9.2. Indica&#231;&#245;es para Ecocardiografia de Estresse</bold> 25</p>
            </list-item>
            <list-item>
              <p><bold>9.3. Protocolos Utilizados na Ecocardiografia de Estresse Diast&#243;lico</bold> 26</p>
            </list-item>
            <list-item>
              <p><bold>9.4. Interpreta&#231;&#227;o da Ecocardiografia de Estresse Diast&#243;lico</bold> 26</p>
            </list-item>
          </list>
        </list-item>
        <list-item>
          <p><bold>10. Ecocardiografia de Estresse no MINOCA (Aus&#234;ncia de Coronariopatia Obstrutiva) e na Doen&#231;a Microvascular</bold> 26</p>
          <list list-type="simple">
            <list-item>
              <p><bold>10.1. Fisiopatologia</bold> 26</p>
            </list-item>
            <list-item>
              <p><bold>10.2. Principais M&#233;todos Diagn&#243;sticos no MINOCA</bold> 26</p>
            </list-item>
            <list-item>
              <p><bold>10.3. Ecocardiografia de Estresse no MINOCA</bold> 28</p>
            </list-item>
          </list>
        </list-item>
        <list-item>
          <p><bold>11. Ecocardiografia de Estresse na Doen&#231;a Valvar Mitral</bold> 29</p>
          <list list-type="simple">
            <list-item>
              <p><bold>11.1. Estenose Mitral</bold> 30</p>
            </list-item>
            <list-item>
              <p><bold>11.2. Regurgita&#231;&#227;o Mitral</bold> 30</p>
            </list-item>
            <list-item>
              <p><bold>11.3. Protocolo de Exame &#8211; Ecocardiografia de Esfor&#231;o para Avalia&#231;&#227;o de Les&#227;o Valvar Mitral</bold> 31</p>
            </list-item>
          </list>
        </list-item>
        <list-item>
          <p><bold>12. Ecocardiografia de Estresse na Doen&#231;a Valvar A&#243;rtica</bold> 31</p>
          <list list-type="simple">
            <list-item>
              <p><bold>12.1. Estenose A&#243;rtica</bold> 31</p>
            </list-item>
            <list-item>
              <p><bold>12.2. Insufici&#234;ncia A&#243;rtica</bold> 33</p>
            </list-item>
          </list>
        </list-item>
        <list-item>
          <p><bold>13. Ecocardiograma de Estresse na Cardiomiopatia Dilatada</bold> 33</p>
        </list-item>
        <list-item>
          <p><bold>14. Ecocardiografia de Estresse na Cardiomiopatia Chag&#225;sica</bold> 35</p>
        </list-item>
        <list-item>
          <p><bold>15. Ecocardiografia de Estresse na Cardiomiopatia Hipertr&#243;fica</bold> 36</p>
        </list-item>
        <list-item>
          <p><bold>16. Ecocardiografia de Estresse na Avalia&#231;&#227;o da Fun&#231;&#227;o do Ventr&#237;culo Direito e na Hipertens&#227;o Pulmonar</bold> 37</p>
        </list-item>
        <list-item>
          <p><bold>17. Ecocardiografia de Estresse na Avalia&#231;&#227;o P&#243;s-COVID-19</bold> 37</p>
        </list-item>
        <list-item>
          <p><bold>18. Ecocardiografia de Estresse e Reserva de Fluxo Coronariano nos Vasos Nativos</bold> 38</p>
        </list-item>
        <list-item>
          <p><bold>19. Ecocardiografia de Estresse e Reserva de Fluxo Coronariano em Enxertos</bold> 39</p>
          <list list-type="simple">
            <list-item>
              <p><bold>19.1. Ecocardiografia de Estresse ap&#243;s Revasculariza&#231;&#227;o Mioc&#225;rdica</bold> 39</p>
            </list-item>
            <list-item>
              <p><bold>19.2. Reserva de Fluxo Coronariano ap&#243;s Revasculariza&#231;&#227;o Mioc&#225;rdica</bold> 39</p>
            </list-item>
          </list>
        </list-item>
        <list-item>
          <p><bold>20. Ecocardiografia de Estresse na An&#225;lise de Viabilidade Mioc&#225;rdica</bold> 41</p>
          <list list-type="simple">
            <list-item>
              <p><bold>20.1. Protocolo de Estresse para An&#225;lise de Viabilidade Mioc&#225;rdica</bold> 41</p>
            </list-item>
            <list-item>
              <p><bold>20.2. An&#225;lise da Viabilidade Mioc&#225;rdica pelo <italic>Strain</italic> Longitudinal</bold> 42</p>
            </list-item>
          </list>
        </list-item>
        <list-item>
          <p><bold>21. Ecocardiografia de Estresse com Agente de Realce Ultrassonogr&#225;fico na An&#225;lise da Borda Endoc&#225;rdica</bold> 42</p>
          <list list-type="simple">
            <list-item>
              <p><bold>21.1. Agente de Realce Ultrassonogr&#225;fico</bold> 43</p>
              <list list-type="simple">
                <list-item>
                  <p><bold>21.1.1. Forma de Administra&#231;&#227;o</bold> 43</p>
                </list-item>
              </list>
            </list-item>
          </list>
        </list-item>
        <list-item>
          <p><bold>22. Ecocardiografia de Estresse com Agente de Realce Ultrassonogr&#225;fico na An&#225;lise da Perfus&#227;o Mioc&#225;rdica</bold> 45</p>
        </list-item>
        <list-item>
          <p><bold>23. Ecocardiografia de Estresse com Strain Mioc&#225;rdico na Cardiopatia Isqu&#234;mica</bold> 46</p>
          <list list-type="simple">
            <list-item>
              <p><bold>23.1. Strain derivado do speckle tracking versus <italic>strain</italic> baseado no Doppler tecidual durante ecocardiografia de estresse</bold> 46</p>
            </list-item>
            <list-item>
              <p><bold>23.2. Ecocardiografia de estresse com <italic>strain</italic> 2D: Valor diagn&#243;stico e progn&#243;stico na doen&#231;a arterial coronariana</bold> 47</p>
            </list-item>
            <list-item>
              <p><bold>23.3. Qual <italic>strain</italic> pode ser &#250;til na ecocardiografia de estresse: global ou regional, longitudinal ou circunferencial? E qual a import&#226;ncia do espessamento p&#243;s-sist&#243;lico?</bold> 48</p>
            </list-item>
            <list-item>
              <p><bold>23.4. O <italic>strain</italic> tem mem&#243;ria isqu&#234;mica?</bold> 49</p>
            </list-item>
            <list-item>
              <p><bold>23.5. O <italic>strain</italic> longitudinal global basal pode predizer doen&#231;a arterial coronariana na aus&#234;ncia de anormalidade parietal visual sob estresse?</bold> 51</p>
            </list-item>
            <list-item>
              <p><bold>23.6. Limita&#231;&#245;es</bold> 51</p>
            </list-item>
          </list>
        </list-item>
        <list-item>
          <p><bold>24. Ecocardiografia de Estresse com Strain Mioc&#225;rdico para Al&#233;m da Cardiopatia Isqu&#234;mica</bold> 52</p>
        </list-item>
        <list-item>
          <p><bold>25. Ecocardiografia de Estresse Tridimensional</bold> 53</p>
          <list list-type="simple">
            <list-item>
              <p><bold>25.1. A Tecnologia da Ecocardiografia Tridimensional e sua Aplica&#231;&#227;o na Imagem do Ecocardiograma</bold> 53</p>
            </list-item>
            <list-item>
              <p><bold>25.2. A Aplica&#231;&#227;o da Ecocardiografia Tridimensional Junto &#224; Ecocardiografia de Estresse</bold> 53</p>
            </list-item>
          </list>
        </list-item>
        <list-item>
          <p><bold>26. A Ecocardiografia de Estresse na Sala de Emerg&#234;ncia: Indica&#231;&#245;es e Aplica&#231;&#245;es</bold> 55</p>
          <list list-type="simple">
            <list-item>
              <p><bold>26.1. Utilidade da Ecocardiografia de Estresse na Emerg&#234;ncia</bold> 55</p>
            </list-item>
          </list>
        </list-item>
        <list-item>
          <p><bold>27. Ecocardiografia de Estresse no P&#243;s-Transplante Card&#237;aco</bold> 57</p>
        </list-item>
        <list-item>
          <p><bold>28. Ecocardiografia de Estresse em Subgrupos Especiais (Bloqueio de Ramo Esquerdo, Bloqueio do Ramo Direito e Fibrila&#231;&#227;o Atrial)</bold> 58</p>
          <list list-type="simple">
            <list-item>
              <p><bold>28.1. Bloqueio de Ramo Esquerdo</bold> 58</p>
            </list-item>
            <list-item>
              <p><bold>28.2. Bloqueio do Ramo Direito</bold> 58</p>
            </list-item>
            <list-item>
              <p><bold>28.3. Fibrila&#231;&#227;o Atrial</bold> 58</p>
            </list-item>
          </list>
        </list-item>
        <list-item>
          <p><bold>29. Ecocardiografia de Estresse no Pr&#233;-Operat&#243;rio de Cirurgia Vascular, em Mulheres e Idosos</bold> 59</p>
          <list list-type="simple">
            <list-item>
              <p><bold>29.1. Pr&#233;-Operat&#243;rio de Cirurgia Vascular</bold> 59</p>
            </list-item>
            <list-item>
              <p><bold>29.2. Mulheres</bold> 59</p>
            </list-item>
            <list-item>
              <p><bold>29.3. Idosos</bold> 60</p>
            </list-item>
          </list>
        </list-item>
        <list-item>
          <p><bold>30. Ecocardiografia de Estresse na Pediatria: Indica&#231;&#245;es e Protocolos</bold> 60</p>
        </list-item>
        <list-item>
          <p><bold>31. Vantagens e Desvantagens da Ecocardiografia de Estresse em Pediatria</bold> 62</p>
        </list-item>
        <list-item>
          <p><bold>32. Progn&#243;stico da Ecocardiografia de Estresse</bold> 63</p>
        </list-item>
        <list-item>
          <p><bold>33. Novas Aplica&#231;&#245;es da Ecocardiografia de Estresse no P&#243;s-Radioterapia de T&#243;rax e no Vasoespasmo</bold> 64</p>
        </list-item>
        <list-item>
          <p><bold>34. Ecocardiografia de Estresse com o Protocolo ABCDE</bold> 64</p>
          <list list-type="simple">
            <list-item>
              <p><bold>34.1. Protocolo ABCDE</bold> 65</p>
            </list-item>
          </list>
        </list-item>
        <list-item>
          <p><bold>35. Recomenda&#231;&#245;es PARA o Manejo da Ecocardiografia de Estresse</bold> 67</p>
        </list-item>
        <list-item>
          <p><bold>Refer&#234;ncias</bold> 68</p>
        </list-item>
      </list>
      <fig id="f1">
        <graphic xlink:href=""/>
        <p>* Pode ser considerado em situa&#231;&#245;es espec&#237;ficas.</p>
      </fig>
    </sec>
    <sec>
      <title>1. O Papel da Ecocardiografia de Repouso Realizada no Momento da Ecocardiografia de Estresse F&#237;sico ou Farmacol&#243;gico</title>
      <p>Uma das primeiras descri&#231;&#245;es do uso da ecocardiografia de estresse de esfor&#231;o (EEE), em 1979, comparou imagens de repouso com aquelas obtidas sob esfor&#231;o em bicicleta.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Quando analisamos as imagens do artigo, ficam claras as limita&#231;&#245;es da &#233;poca, com a dificuldade de interpretar imagens em repouso e ao esfor&#231;o devido &#224; sua defini&#231;&#227;o. Mesmo assim, altera&#231;&#245;es segmentares observadas em 10 pacientes foram encontradas naqueles com estenoses coron&#225;rias importantes. O m&#233;todo evoluiu desde ent&#227;o e o exame de repouso passou a contar com ferramentas diagn&#243;sticas mais apuradas, como Doppler em diversas modalidades, grava&#231;&#227;o digital de ciclos com alta taxa de quadros, medidas confi&#225;veis de volumes cavit&#225;rios, an&#225;lise da deforma&#231;&#227;o de ventr&#237;culos e &#225;trios, estimativas das press&#245;es cavit&#225;rias, an&#225;lise de &#225;reas valvares e v&#225;rios marcadores de risco pass&#237;veis de an&#225;lise ao repouso. Essa an&#225;lise ampla e complexa em repouso, com avalia&#231;&#227;o morfol&#243;gica e funcional completa, estabeleceu o exame de repouso como modalidade isolada.</p>
      <p>Picano et al., em um consenso europeu recente,<sup><xref ref-type="bibr" rid="B2">2</xref></sup> definiram a ecocardiografia de repouso, realizada junto ao eco estresse, com fun&#231;&#245;es restritas, como an&#225;lise da qualidade das imagens, mapeamento das janelas padr&#227;o, exclus&#227;o de outras raz&#245;es &#243;bvias para os sintomas (por exemplo, derrame peric&#225;rdico, estenose a&#243;rtica, cardiomiopatia hipertr&#243;fica) e sobretudo, elimina&#231;&#227;o de contraindica&#231;&#245;es ao exame com estresse, como isquemia aguda, dissec&#231;&#227;o da aorta e embolia pulmonar, entre outras. Como definida nesse consenso e em outras diretrizes,<sup><xref ref-type="bibr" rid="B3">3</xref></sup> a ecocardiografia de repouso realizada imediatamente antes da ecocardiografia de estresse n&#227;o &#233; completa, pois tem a finalidade de observar os par&#226;metros que podem sofrer altera&#231;&#245;es din&#226;micas. Portanto, um olhar direcionado &#224; indica&#231;&#227;o cl&#237;nica do m&#233;todo e &#224;s altera&#231;&#245;es em repouso que devem ser avaliadas sob estresse n&#227;o pode ser utilizada ou requerida como avalia&#231;&#227;o morfol&#243;gica e funcional completa de uma ecocardiografia padr&#227;o.</p>
      <p>Assim, a ecocardiografia convencional de repouso &#233; um exame diferenciado e deve ser solicitada, preferencialmente, em outro momento. Mais do que isso, trata-se do exame anterior e de primeira linha para afastar as situa&#231;&#245;es que limitam, contraindicam ou impedem a realiza&#231;&#227;o da ecocardiografia de estresse, como os exemplos citados acima, e a pr&#243;pria imagem do paciente, que pode ser limitada ao ultrassom, comprometendo a avalia&#231;&#227;o da ecocardiografia de estresse.</p>
    </sec>
    <sec>
      <title>2. A Evolu&#231;&#227;o da Ecocardiografia de Estresse: do Princ&#237;pio aos Dias de Hoje</title>
      <p>A doen&#231;a arterial coronariana (DAC) continua a ser uma causa importante de morbimortalidade e, portanto, recursos diagn&#243;sticos e terap&#234;uticos capazes de reduzir esse panorama permanecem objetos de grande interesse na &#225;rea m&#233;dica, do ponto de vista individual e comunit&#225;rio, com impacto socioecon&#244;mico relevante.</p>
      <p>A exist&#234;ncia de m&#233;todos diagn&#243;sticos acess&#237;veis, de f&#225;cil execu&#231;&#227;o, boa reprodutibilidade, baixo custo, preferencialmente n&#227;o invasivos e com boa acur&#225;cia sempre interessaram &#224;s linhas de pesquisa na cardiologia, especialmente no que se refere &#224; doen&#231;a coronariana.</p>
      <p>O uso de f&#225;rmacos para ocasionar o desequil&#237;brio entre oferta e consumo de oxig&#234;nio inicialmente era associado &#224; eletrocardiografia com o uso de dipiridamol, posteriormente substitu&#237;do pela dobutamina. Por&#233;m, o uso desses f&#225;rmacos associados &#224; ecocardiografia se estabeleceu a partir dos estudos iniciais de Picano et al., que utilizavam dipiridamol, e de Berthe e Pi&#233;rard em 1986, que utilizavam dobutamina.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Na pr&#225;tica cl&#237;nica di&#225;ria, esses f&#225;rmacos prevaleceram em termos de uso, com protocolos de dose bem definidos, crit&#233;rios diagn&#243;sticos e n&#237;veis de seguran&#231;a estabelecidos, muitas vezes associados ao uso da atropina, com a finalidade de maximizar os n&#237;veis de frequ&#234;ncia card&#237;aca (FC) e, assim, otimizar os &#237;ndices diagn&#243;sticos.<sup><xref ref-type="bibr" rid="B6">6</xref>-<xref ref-type="bibr" rid="B13">13</xref></sup></p>
      <p>A op&#231;&#227;o pelo esfor&#231;o f&#237;sico, seja ele realizado em esteiras ou bicicletas ergom&#233;tricas ou em cicloerg&#244;metros, por ser um m&#233;todo mais fisiol&#243;gico, continua a ser a modalidade de estresse de primeira escolha para pacientes com capacidade f&#237;sica e condi&#231;&#245;es para a realiza&#231;&#227;o do esfor&#231;o. Em pacientes com limita&#231;&#245;es ao exame sob esfor&#231;o f&#237;sico, como aqueles com sequelas ortop&#233;dicas ou neurol&#243;gicas, pneumopatias, limita&#231;&#245;es visuais ou incoordena&#231;&#227;o para execu&#231;&#227;o da atividade f&#237;sica, entre outras, a alternativa &#233; o uso de protocolos farmacol&#243;gicos.<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
      <p>Tanto a modalidade de esfor&#231;o f&#237;sico quanto os testes farmacol&#243;gicos se mostraram, dados os resultados obtidos nas &#250;ltimas d&#233;cadas, seguros para a avalia&#231;&#227;o de coronariopatas, idosos, mulheres, pacientes renais cr&#244;nicos, valvopatas, transplantados e portadores de doen&#231;as vasculares perif&#233;ricas. Ambos apresentam &#237;ndices diagn&#243;sticos valiosos, semelhantes aos m&#233;todos da medicina nuclear, e com altos &#237;ndices de concord&#226;ncia com m&#233;todos anat&#244;micos estruturais, como a angiotomografia e a cineangiocoronariografia.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B14">14</xref>,<xref ref-type="bibr" rid="B16">16</xref></sup></p>
      <p>Deve-se ressaltar que, al&#233;m da finalidade de detec&#231;&#227;o de isquemia mioc&#225;rdica, a ecocardiografia sob estresse &#233; extremamente valiosa para a pesquisa de viabilidade mioc&#225;rdica em pacientes com evento pr&#233;vio, conceito fisiopatol&#243;gico de import&#226;ncia diagn&#243;stica, terap&#234;utica e progn&#243;stica para os portadores de coronariopatia.<sup><xref ref-type="bibr" rid="B10">10</xref>-<xref ref-type="bibr" rid="B12">12</xref></sup></p>
      <p>Por fim, observa-se que, al&#233;m dos limites da doen&#231;a coronariana, o m&#233;todo j&#225; &#233; amplamente indicado na avalia&#231;&#227;o de altera&#231;&#245;es da fun&#231;&#227;o diast&#243;lica, especialmente entre pacientes com insufici&#234;ncia card&#237;aca com fra&#231;&#227;o de eje&#231;&#227;o preservada (ICFEp), cardiomiopatias n&#227;o isqu&#234;micas (doen&#231;as de dep&#243;sito e infiltrativas), avalia&#231;&#227;o de doen&#231;as valvares mitral e a&#243;rtica, estudo de cardiopatias cong&#234;nitas, hipertens&#227;o pulmonar, avalia&#231;&#227;o do cora&#231;&#227;o do atleta, avalia&#231;&#227;o de doen&#231;a vascular do enxerto e no p&#243;s-transplante, entre outros.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B14">14</xref>-<xref ref-type="bibr" rid="B20">20</xref></sup></p>
    </sec>
    <sec sec-type="methods">
      <title>3. M&#233;todos Provocativos de Isquemia</title>
      <p>O objetivo principal da EEE na DAC &#233; demonstrar o desenvolvimento da isquemia mioc&#225;rdica, sua extens&#227;o e distribui&#231;&#227;o e, secundariamente, a estratifica&#231;&#227;o de risco por meio de altera&#231;&#245;es hemodin&#226;micas (dilata&#231;&#227;o ventricular, queda da press&#227;o arterial [PA], disfun&#231;&#227;o diast&#243;lica, altera&#231;&#227;o da reserva de fluxo coronariano [RFC] e/ou reserva mioc&#225;rdica [RM], entre outras).<sup><xref ref-type="bibr" rid="B21">21</xref></sup></p>
      <p>A isquemia mioc&#225;rdica pode ser evidente na presen&#231;a de les&#245;es epic&#225;rdicas obstrutivas importantes (art&#233;ria coron&#225;ria principal esquerda (tronco da coron&#225;ria esquerda) &gt; 50% ou les&#245;es epic&#225;rdicas &gt; 70%) ou na presen&#231;a de microcircula&#231;&#227;o comprometida sem les&#245;es epic&#225;rdicas importantes. A utilidade de cada teste se baseia na detec&#231;&#227;o dessas anormalidades<sup><xref ref-type="bibr" rid="B22">22</xref></sup> (<xref ref-type="fig" rid="f2">Figura 3.1</xref>).</p>
      <fig id="f2">
        <label>Figura 3.1</label>
        <caption>
          <title>Objetivos anat&#244;micos e funcionais da ecocardiografia de estresse. TCE: tronco da coron&#225;ria esquerda; AE: art&#233;ria epic&#225;rdica; RFC: reserva de fluxo coronariano; RM: reserva mioc&#225;rdica; BRE: bloqueio de ramo esquerdo.</title>
        </caption>
        <graphic xlink:href=""/>
      </fig>
      <p>Tamb&#233;m &#233; interessante buscar a queda do fluxo em les&#245;es intermedi&#225;rias n&#227;o importantes, sem isquemia em testes convencionais, por meio da medida da RFC.<sup><xref ref-type="bibr" rid="B23">23</xref></sup></p>
      <sec>
        <title>3.1. Ecocardiografia de Estresse com Exerc&#237;cio (Bicicleta, Esteira Ergom&#233;trica ou Ciclomaca)</title>
        <p>&#201; o mais fisiol&#243;gico dos testes provocativos, baseado na demonstra&#231;&#227;o de isquemia por meio do aumento do duplo produto (PA sist&#243;lica [PAS] m&#225;xima &#215; FC m&#225;xima alcan&#231;ada) e do consumo de oxig&#234;nio mioc&#225;rdico, e considerado a primeira escolha (exceto em caso de contraindica&#231;&#245;es ou de indisponibilidade do centro). &#201; mais &#250;til em les&#245;es epic&#225;rdicas importantes, acometendo principalmente a camada subendoc&#225;rdica, avaliada pela motilidade parietal (espessamento), extens&#227;o e distribui&#231;&#227;o, com risco significativo quando o envolvimento &#233; de tr&#234;s ou mais segmentos. Al&#233;m disso, permite a observa&#231;&#227;o simult&#226;nea das repercuss&#245;es hemodin&#226;micas da isquemia: disfun&#231;&#227;o diast&#243;lica (fluxo transmitral, E/e&#8217;), dilata&#231;&#227;o ventricular, insufici&#234;ncia mitral, queda da reserva mioc&#225;rdica, arritmias e linhas B pulmonares, entre outras.</p>
      </sec>
      <sec>
        <title>3.2 Ecocardiografia de Estresse Farmacol&#243;gico</title>
        <list list-type="alpha-lower">
          <list-item>
            <p>Dobutamina: baseia-se na demonstra&#231;&#227;o de isquemia em les&#245;es epic&#225;rdicas importantes, por meio do aumento do duplo produto e do consumo de oxig&#234;nio mioc&#225;rdico pela a&#231;&#227;o nos receptores adren&#233;rgicos que aumenta o inotropismo e cronotropismo card&#237;acos. &#201; utilizado em pacientes que n&#227;o conseguem realizar exerc&#237;cio, quando a EEE n&#227;o est&#225; dispon&#237;vel ou em pacientes com anormalidades de motilidade regional basal em busca de isquemia e viabilidade (este &#250;ltimo ainda em discuss&#227;o). Tem a mesma utilidade da EEE.</p>
          </list-item>
          <list-item>
            <p>Vasodilatadores (dipiridamol e adenosina): atuam na microcircula&#231;&#227;o, demonstrando isquemia por meio da vasodilata&#231;&#227;o direta das arter&#237;olas saud&#225;veis, em detrimento das arter&#237;olas doentes, causando o "efeito de roubo de fluxo da art&#233;ria coron&#225;ria com obstru&#231;&#227;o". Isso ocorre pelo ac&#250;mulo da adenosina no sistema vascular (de modo indireto com o dipiridamol e direto com adenosina ex&#243;gena), cuja a&#231;&#227;o vasodilatadora &#233; muito potente. Esses f&#225;rmacos n&#227;o aumentam significativamente o duplo produto, o que permite uma avalia&#231;&#227;o mais pr&#225;tica da RFC e do <italic>strain</italic> mioc&#225;rdico. S&#227;o &#250;teis em pacientes com bloqueio completo do ramo esquerdo (BCRE), marca-passo permanente, contraindica&#231;&#227;o para exerc&#237;cio ou dobutamina, suspeita de doen&#231;a microvascular, fibrila&#231;&#227;o atrial, hipertens&#227;o arterial e sintom&#225;ticos com les&#245;es epic&#225;rdicas.</p>
          </list-item>
        </list>
      </sec>
      <sec>
        <title>3.3. Ecocardiografia de Estresse no Espasmo Coron&#225;rio</title>
        <list list-type="alpha-lower">
          <list-item>
            <p>Teste de ergonovina: &#233; o padr&#227;o ouro devido &#224; sua alta sensibilidade (93%) e especificidade (91%). Estimula os receptores &#945;-adren&#233;rgicos.<sup><xref ref-type="bibr" rid="B24">24</xref>-<xref ref-type="bibr" rid="B26">26</xref></sup></p>
          </list-item>
          <list-item>
            <p>5-hidroxitriptamina (serotonina): tem alto risco e n&#227;o &#233; indicada para uso rotineiro, de modo que n&#227;o obteve reprodutibilidade cl&#237;nica. As altera&#231;&#245;es contr&#225;teis que indicam isquemia s&#227;o precoces, antes mesmo da dor ou de altera&#231;&#245;es eletrocardiogr&#225;ficas, e podem induzir a s&#237;ndrome de Takotsubo.<sup><xref ref-type="bibr" rid="B27">27</xref></sup></p>
          </list-item>
          <list-item>
            <p>Teste de hiperventila&#231;&#227;o: provoca espasmo coron&#225;rio por meio da diminui&#231;&#227;o do &#237;on H+ no plasma com aumento do pH (alcalose) e do aumento do c&#225;lcio intracelular, causando uma contra&#231;&#227;o e vasoespasmos das c&#233;lulas musculares lisas das art&#233;rias coron&#225;rias epic&#225;rdicas. Sua sensibilidade &#233; alta (90%).<sup><xref ref-type="bibr" rid="B28">28</xref>,<xref ref-type="bibr" rid="B29">29</xref></sup></p>
          </list-item>
          <list-item>
            <p>Teste press&#243;rico ao frio (<italic>cold pressor test</italic>): na presen&#231;a de disfun&#231;&#227;o endotelial e eleva&#231;&#227;o de catecolaminas, ocorre vasoconstri&#231;&#227;o coronariana.<sup><xref ref-type="bibr" rid="B28">28</xref>,<xref ref-type="bibr" rid="B29">29</xref></sup></p>
          </list-item>
          <list-item>
            <p>A combina&#231;&#227;o da ecocardiografia de estresse f&#237;sico (EEF) ou dobutamina associado ao teste press&#243;rico ao frio e/ou &#224; hiperventila&#231;&#227;o pode aumentar a sensibilidade e o poder diagn&#243;stico do vasoespasmo coronariano.</p>
          </list-item>
        </list>
      </sec>
      <sec>
        <title>3.4. Ecocardiografia de Estresse com Marca-Passo</title>
        <p>Utilizado em pacientes portadores de marca-passo definitivo (MCPD), com estimula&#231;&#227;o de &#225;trio direito e/ou ventr&#237;culo direito. O mecanismo &#233; o aumento da FC, que aumenta o duplo produto e causa isquemia. A avalia&#231;&#227;o do espessamento regional leva em considera&#231;&#227;o os movimentos septais causados pelo local de implanta&#231;&#227;o do cateter marca-passo (<xref ref-type="fig" rid="f3">Figura 3.2</xref>).</p>
        <fig id="f3">
          <label>Figura 3.2</label>
          <caption>
            <title>Ecocardiografia de estresse por marca-passo de acordo com a c&#226;mara estimulada e movimento septal.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>&#201; altamente sens&#237;vel (98%) e seguro (96%), pois pode reduzir instantaneamente a FC.<sup><xref ref-type="bibr" rid="B30">30</xref>,<xref ref-type="bibr" rid="B31">31</xref></sup></p>
        <p>Trata-se de uma boa alternativa diagn&#243;stica de isquemia em pacientes que n&#227;o podem realizar exerc&#237;cio, t&#234;m contraindica&#231;&#227;o ao teste farmacol&#243;gico ou portam marca-passo (<xref ref-type="fig" rid="f3">Figura 3.2</xref>).</p>
      </sec>
    </sec>
    <sec>
      <title>4. Ecocardiografia de Estresse F&#237;sico (Esteira, Bicicleta e Ciclomaca)</title>
      <p>A EEF &#233; um exame que investiga a funcionalidade do mioc&#225;rdio de forma eficaz, fisiol&#243;gica e segura, procurando reproduzir o dia a dia de indiv&#237;duos com capacidade f&#237;sica preservada. De maneira pr&#225;tica e n&#227;o invasiva, permite obter informa&#231;&#245;es valiosas sobre o diagn&#243;stico de isquemia mioc&#225;rdica, comportamento da PA sist&#234;mica, etiologia de arritmias card&#237;acas e avalia&#231;&#227;o do comportamento dos gradientes de press&#227;o da via de sa&#237;da do ventr&#237;culo esquerdo (VSVE), da PAS pulmonar e de les&#245;es valvares. &#201; importante ressaltar que a an&#225;lise desses par&#226;metros deve ser correlacionada com a poss&#237;vel ocorr&#234;ncia de sintomas antes, durante e ap&#243;s o esfor&#231;o f&#237;sico.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Nas &#250;ltimas duas d&#233;cadas, foi demostrada a utilidade dessa metodologia para o manejo de portadores de diversas patologias, tais como, coronariopatias, cardiomiopatias, valvopatias, arritmias card&#237;acas, entre outras, sendo &#250;til tamb&#233;m na estratifica&#231;&#227;o de risco no pr&#233;-operat&#243;rio de procedimentos cir&#250;rgicos n&#227;o card&#237;acos.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
      <p>Frente &#224;s novas modalidades de imagens card&#237;acas, como angiotomografia das coron&#225;rias (ATC) e a resson&#226;ncia magn&#233;tica do cora&#231;&#227;o (RNM-C), a EEF, surpreendentemente, evoluiu bastante. Embora a RNM-C tenha demonstrado a capacidade indiscut&#237;vel de diagnosticar, de forma detalhada, diversas patologias card&#237;acas, a acur&#225;cia da RNM-C no diagn&#243;stico de isquemia mioc&#225;rdica n&#227;o &#233; superior &#224; da EEF ou &#224; da cintilografia do mioc&#225;rdio. E por ser uma metodologia de f&#225;cil acesso, baixo custo e alta reprodutibilidade, a EEF &#233; de grande utilidade para o acompanhamento dos portadores dessas cardiopatias.<sup><xref ref-type="bibr" rid="B33">33</xref></sup> &#201; importante que as novas gera&#231;&#245;es de ecocardiografistas tamb&#233;m se interessem pelo m&#233;todo, tanto como exame &#250;til na investiga&#231;&#227;o cl&#237;nica, como na pesquisa cient&#237;fica, buscando sempre se aprimorar na obten&#231;&#227;o de imagens de qualidade satisfat&#243;ria de modo a n&#227;o comprometer a interpreta&#231;&#227;o dos resultados.<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
      <p>Inicialmente, o ecocardiografista deve avaliar as condi&#231;&#245;es cl&#237;nicas do paciente, bem como a sua prefer&#234;ncia entre esteira, bicicleta ergom&#233;trica ou ciclomaca, caso o servi&#231;o disponha de mais de uma op&#231;&#227;o. Tamb&#233;m &#233; importante discutir as limita&#231;&#245;es das ferramentas estressoras, de forma que a escolha seja embasada na capacidade f&#237;sica do paciente, assim como nas condi&#231;&#245;es locais de cada servi&#231;o. &#201; importante, ainda, que o paciente seja informado que a EEF &#233; composta de quatro componentes: eletrocardiografia, teste ergom&#233;trico, ecocardiografia transtor&#225;cica direcionada e ecocardiografia de estresse, considerando tamb&#233;m a sintomatologia e capacidade f&#237;sica do paciente. Cabe ao ecocardiografista ficar atento &#224; execu&#231;&#227;o de todas as etapas do exame: o repouso, o pr&#233;-teste, a fase de esfor&#231;o e, por fim, a fase de recupera&#231;&#227;o. A presen&#231;a de param&#233;dicos durante todo o exame tamb&#233;m se faz necess&#225;ria, para que n&#227;o sejam comprometidas as grava&#231;&#245;es dos tra&#231;ados eletrocardiogr&#225;ficos e as imagens ecocardiogr&#225;ficas.</p>
      <p>Na maioria dos servi&#231;os, a esteira ergom&#233;trica constitui o carro-chefe, sobretudo por ser a metodologia de prefer&#234;ncia da maioria dos pacientes. Com ela, o ecocardiografista experiente consegue, na maioria das vezes, que o paciente atinja a FC m&#225;xima preconizada (220 &#8722; idade), sobretudo se conscientizado dessa necessidade. Contudo, a imagem ao ecocardiograma muitas vezes fica prejudicada quando o esfor&#231;o m&#225;ximo &#233; alcan&#231;ado devido &#224; presen&#231;a do pulm&#227;o pela hiperventila&#231;&#227;o, ent&#227;o recomenda-se alcan&#231;ar uma frequ&#234;ncia intermedi&#225;ria entre a subm&#225;xima (85% da m&#225;xima) e a m&#225;xima para a boa interpreta&#231;&#227;o das imagens, uma vez que s&#227;o estas que definir&#227;o o teste e devem ser obtidas, idealmente, at&#233; 90 segundos ap&#243;s o esfor&#231;o m&#225;ximo (na esteira ergom&#233;trica). Essa conduta facilita a aquisi&#231;&#227;o e a grava&#231;&#227;o das imagens ecocardiogr&#225;ficas, no pico do esfor&#231;o f&#237;sico, com o paciente j&#225; deitado na maca, em dec&#250;bito lateral esquerdo, o que deve ser obtido rapidamente ap&#243;s a aquisi&#231;&#227;o da FC almejada, para n&#227;o reduzir a sensibilidade do teste. J&#225; quando a bicicleta ergom&#233;trica &#233; utilizada, o momento da parada do exerc&#237;cio &#233; quase sempre definido pelo paciente (desde que alcance a FC almejada para que o teste seja conclusivo), e a capta&#231;&#227;o de imagem, realizada durante o esfor&#231;o e na posi&#231;&#227;o sentada, &#233; mais laborioso para o ecocardiografista. Isso levou &#224; inven&#231;&#227;o da ciclomaca, que facilita a capta&#231;&#227;o de imagens, uma vez que o indiv&#237;duo se encontra em posi&#231;&#227;o semissupina durante todo o exame.<sup><xref ref-type="bibr" rid="B32">32</xref></sup> Nesse caso, a posi&#231;&#227;o com maior eleva&#231;&#227;o da ciclomaca permite um teste de melhor qualidade, dada maior propuls&#227;o das pernas que o paciente obt&#233;m.</p>
      <p>Atualmente, al&#233;m das indica&#231;&#245;es cl&#225;ssicas da EEF que envolvem os pacientes que podem se exercitar e referem dor tor&#225;cica, DAC suspeita ou conhecida, cansa&#231;o ou suspeita de ICFEp, as diretrizes da American Heart Association de cardiomiopatia hipertr&#243;fica (CMH) de 2021<sup><xref ref-type="bibr" rid="B33">33</xref></sup> recomendam a avalia&#231;&#227;o inicial da medida do gradiente de VSVE de todos os pacientes com CMH em repouso, durante a manobra de Valsalva, nas posi&#231;&#245;es semissupina, sentada ou ereta. Para pacientes assintom&#225;ticos e com gradiente de VSVE de repouso &lt; 50 mmHg, indica-se a realiza&#231;&#227;o da EEF, que considera CMH obstrutiva quando o gradiente supera 50 mmHg. O gradiente de VSVE l&#225;bil ou obstrutivo &#233; definido como aquele n&#227;o observado durante a ecocardiografia em repouso, mas induzido pelo teste de esfor&#231;o. Tamb&#233;m &#233; importante ressaltar que um gradiente de VSVE &#8805; 50 mmHg em repouso contraindica a EEF. Al&#233;m disso, &#233; preciso avaliar a presen&#231;a de movimento sist&#243;lico anterior da valva mitral, regurgita&#231;&#227;o mitral, assinergia ventricular e disfun&#231;&#227;o diast&#243;lica grau 3.<sup><xref ref-type="bibr" rid="B34">34</xref></sup> (<xref ref-type="fig" rid="f4">Figura 4.1</xref>).</p>
      <fig id="f4">
        <label>Figura 4.1</label>
        <caption>
          <title>Fluxograma proposto para utiliza&#231;&#227;o de ecocardiografia de estresse f&#237;sico em pacientes com CMH sem gradiente (GVSVE = 0 mmHg) ou com GVSVE (&lt; 50 mmHg). CMH: cardiomiopatia hipertr&#243;fica; GVSVE: gradiente da via de sa&#237;da do ventr&#237;culo esquerdo; VE: ventr&#237;culo esquerdo.</title>
        </caption>
        <graphic xlink:href=""/>
      </fig>
      <p>Os protocolos da EEF nas modalidades de bicicleta ergom&#233;trica, esteira ergom&#233;trica e ciclomaca se encontram na <xref ref-type="fig" rid="f5">Figura 4.2</xref>.</p>
      <fig id="f5">
        <label>Figura 4.2</label>
        <caption>
          <title>Protocolos da ecocardiografia de estresse f&#237;sico nas modalidades de bicicleta ergom&#233;trica, esteira ergom&#233;trica e ciclomaca (supina). A captura da imagem na bicicleta e na ciclomaca &#233; cont&#237;nua, enquanto na esteira ergom&#233;trica ocorre somente antes e ap&#243;s o esfor&#231;o imediato. O protocolo de Bruce ainda &#233; muito utilizado na esteira ergom&#233;trica, enquanto na bicicleta ou ciclomaca utiliza-se preferencialmente o protocolo de Balke com incremento de carga a cada 2 minutos (incrementos de 25 W), conforme figura,<sup><xref ref-type="bibr" rid="B2">2</xref></sup> podendo ir al&#233;m de 125W.</title>
        </caption>
        <graphic xlink:href=""/>
      </fig>
    </sec>
    <sec>
      <title>5. Ecocardiografia de Estresse com Dobutamina na Avalia&#231;&#227;o de Isquemia Mioc&#225;rdica</title>
      <p>Na isquemia mioc&#225;rdica, a base da ecocardiografia de estresse farmacol&#243;gico com dobutamina (EED) &#233; a avalia&#231;&#227;o da resposta fisiol&#243;gica do mioc&#225;rdio a diferentes graus de obstru&#231;&#227;o da art&#233;ria coron&#225;ria, especialmente na perfus&#227;o subendoc&#225;rdica, enquanto a camada subepic&#225;rdica &#233; afetada apenas em est&#225;gio posterior, se a isquemia persiste.<sup><xref ref-type="bibr" rid="B35">35</xref>,<xref ref-type="bibr" rid="B36">36</xref></sup></p>
      <p>A EED &#233; uma modalidade alternativa para avalia&#231;&#227;o de isquemia mioc&#225;rdica quando o paciente n&#227;o consegue realizar exerc&#237;cio f&#237;sico, inicialmente desenvolvida para avalia&#231;&#227;o de pacientes com DAC conhecida ou suspeita.<sup><xref ref-type="bibr" rid="B37">37</xref></sup> A indica&#231;&#227;o mais frequente da EED &#233; para avalia&#231;&#227;o da presen&#231;a, localiza&#231;&#227;o ou extens&#227;o de isquemia mioc&#225;rdica com especificidade de 88% que resulta em alto valor preditivo negativo para infarto do mioc&#225;rdio e &#243;bito card&#237;aco.<sup><xref ref-type="bibr" rid="B38">38</xref></sup>A <xref ref-type="table" rid="t2">Tabela 5.1</xref> apresenta as indica&#231;&#245;es para EED nas diretrizes.<sup><xref ref-type="bibr" rid="B39">39</xref></sup></p>
      <table-wrap id="t2">
        <label>Tabela 5.1</label>
        <caption>
          <title>Indica&#231;&#245;es da ecocardiografia de estresse farmacol&#243;gico com dobutamina na isquemia mioc&#225;rdica<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B12">12</xref>,<xref ref-type="bibr" rid="B35">35</xref>-<xref ref-type="bibr" rid="B43">43</xref></sup></title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup width="100%">
            <col/>
          </colgroup>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr>
              <td align="left" valign="middle">1) Diagn&#243;stico de DAC com probabilidade pr&#233;-teste intermedi&#225;ria.</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">2) Dor tor&#225;cica aguda em pacientes de risco intermedi&#225;rio (sem anormalidades no eletrocardiograma e biomarcadores negativos).</td>
            </tr>
            <tr>
              <td align="left" valign="middle">3) Sintoma de angina em pacientes com stent ou revasculariza&#231;&#227;o pr&#233;vios.</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">4) Obstru&#231;&#227;o coron&#225;ria moderada &#224; angiotomografia ou angiografia coron&#225;ria: significado funcional.</td>
            </tr>
            <tr>
              <td align="left" valign="middle">5) Estratifica&#231;&#227;o de risco p&#243;s-infarto do mioc&#225;rdio.</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">6) Etiologia de dispneia.</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <p>A EED pode n&#227;o detectar isquemia de pequenos vasos distais e pacientes com obesidade ou enfisema podem ter janelas ac&#250;sticas ruins, resultando em imagens sub&#243;timas mesmo com o uso do agente de realce ultrassonogr&#225;fico (ARUS) ou contraste para ultrassom.</p>
      <p>A sele&#231;&#227;o do exame apropriado se baseia no quadro cl&#237;nico do paciente, incluindo a natureza dos sintomas, o perfil de risco, os pontos fortes e as limita&#231;&#245;es da modalidade escolhida.<sup><xref ref-type="bibr" rid="B40">40</xref></sup></p>
      <p>Para os equipamentos e medicamentos necess&#225;rios para a realiza&#231;&#227;o da EED, consulte a <xref ref-type="table" rid="t3">Tabela 5.2</xref>.<sup><xref ref-type="bibr" rid="B39">39</xref></sup></p>
      <table-wrap id="t3">
        <label>Tabela 5.2</label>
        <caption>
          <title>Equipamento e medicamentos necess&#225;rios para a realiza&#231;&#227;o da ecocardiografia de estresse farmacol&#243;gico com dobutamina<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B12">12</xref>,<xref ref-type="bibr" rid="B35">35</xref>-<xref ref-type="bibr" rid="B43">43</xref></sup></title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup width="100%">
            <col/>
          </colgroup>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr>
              <td align="left" valign="middle">1) Ecocardi&#243;grafo digital com protocolo de estresse para avalia&#231;&#227;o simult&#226;nea de imagens no formato <italic>quad screen.</italic></td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">2) Aparelho para monitoriza&#231;&#227;o (preferencialmente cont&#237;nua) de eletrocardiograma e de press&#227;o arterial.</td>
            </tr>
            <tr>
              <td align="left" valign="middle">3) Equipamento e medicamentos para ressuscita&#231;&#227;o cardiopulmonar com desfibrilador/cardioversor.</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">4) Oxig&#234;nio para suprimento (se necess&#225;rio).</td>
            </tr>
            <tr>
              <td align="left" valign="middle">5) Equipamento para intuba&#231;&#227;o.</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">6) Bomba de infus&#227;o para dobutamina.</td>
            </tr>
            <tr>
              <td align="left" valign="middle">7) Drogas para rea&#231;&#227;o al&#233;rgica, al&#233;m de dobutamina, atropina e metoprolol (e de outros f&#225;rmacos e seus ant&#237;dotos, caso o protocolo farmacol&#243;gico seja outro).</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <sec>
        <title>5.1. Protocolo da Ecocardiografia de Estresse Farmacol&#243;gico com Dobutamina</title>
        <p>O protocolo foi definido em 2007 pela American Society of Echocardiography em suas diretrizes.<sup><xref ref-type="bibr" rid="B12">12</xref></sup></p>
        <p>Preparo do paciente: Os pacientes devem estar em jejum por 4 a 6 horas antes do exame e podem continuar com seus medicamentos regulares. Por&#233;m, devem ser interrompidos pelo menos 24 horas antes do teste: amiodarona, bloqueadores dos canais de c&#225;lcio, nitratos, medicamentos que cont&#234;m cafe&#237;na e nicotina (particularmente para o estresse com dipiridamol) e, especialmente, betabloqueadores (para evitar resultado falso negativo).<sup><xref ref-type="bibr" rid="B37">37</xref></sup> Idealmente, os &#250;ltimos devem ser interrompidos 3 a 4 dias antes do exame caso o objetivo seja o diagn&#243;stico de isquemia mioc&#225;rdica.</p>
        <p>Etapas do procedimento: 1) acesso endovenoso; 2) eletrodos em 12 deriva&#231;&#245;es; 3) coloca&#231;&#227;o do esfigmoman&#244;metro; 4) ecocardiografia dirigida em repouso, para compara&#231;&#227;o das imagens sob estresse; 5) aquisi&#231;&#227;o de imagens da ecocardiografia de repouso, dose baixa, intermedi&#225;ria (opcional), pico de dobutamina e fase de recupera&#231;&#227;o, com cineloops para fins de registro nos cortes principais: eixo longo, eixo curto do VE (n&#237;vel dos m&#250;sculos papilares), apical de quatro c&#226;maras, apical de duas c&#226;maras e opcional, o apical de tr&#234;s c&#226;maras (valor adicional para avalia&#231;&#227;o do &#225;pice do VE ou em substitui&#231;&#227;o do paraesternal longitudinal). Alguns autores optam pela aquisi&#231;&#227;o de todos os cortes pela janela apical (cortes apicais de quatro, tr&#234;s e duas c&#226;maras). &#201; importante contemplar todas as paredes do VE irrigadas pelos principais vasos coronarianos; 6) monitoriza&#231;&#227;o cont&#237;nua do eletrocardiograma (ECG), da FC e da PA; 7) Se necess&#225;rio, &#233; realizado o esfor&#231;o isom&#233;trico (<italic>handgrip</italic>) em associa&#231;&#227;o; infus&#227;o de atropina para potencializar o exame; e infus&#227;o de metoprolol para antagonizar os efeitos da dobutamina (quando necess&#225;rio); 8) relat&#243;rio do exame.</p>
        <p>A&#231;&#227;o e farmacocin&#233;tica da dobutamina: A dobutamina apresenta forte efeito agonista adren&#233;rgico que atua nos receptores adren&#233;rgicos B1 para aumentar a FC e a contratilidade e nos receptores B2 para provocar vasodilata&#231;&#227;o perif&#233;rica. Sua a&#231;&#227;o tem in&#237;cio 1 a 2 minutos ap&#243;s a infus&#227;o e tem meia-vida de 2 minutos. A dobutamina &#233; o agente mais utilizado devido &#224; sua alta sensibilidade e efeitos colaterais control&#225;veis.<sup><xref ref-type="bibr" rid="B37">37</xref></sup> Tem metaboliza&#231;&#227;o hep&#225;tica e nos tecidos perif&#233;ricos, mas n&#227;o h&#225; necessidade de redu&#231;&#227;o da dose definida para pacientes com disfun&#231;&#227;o renal ou hep&#225;tica. Em geral, &#233; administrada em doses crescentes, come&#231;ando com 5 mcg/kg/min e aumentando em intervalos de 3 minutos at&#233; 10, 20, 30 e 40 mcg/kg/min. A dobutamina pode ser iniciada na dose baixa de 2,5 mcg/kg/min; e passar pela dose de 7,5 mcg/kg/min para facilitar o reconhecimento da viabilidade mioc&#225;rdica em segmentos anormais (acin&#233;ticos) no repouso.</p>
        <p>A meta &#233; alcan&#231;ar a FC alvo (85% da FC m&#225;xima prevista para a idade), o que torna o teste conclusivo. Contudo, nova altera&#231;&#227;o da contratilidade ou uma piora das altera&#231;&#245;es anteriores leva &#224; interrup&#231;&#227;o do exame por isquemia, mas arritmias importantes, hipertens&#227;o arterial acentuada e sintomas intoler&#225;veis tamb&#233;m podem levar a interrup&#231;&#227;o do teste. Quando n&#227;o &#233; poss&#237;vel alcan&#231;ar a FC alvo apenas com dobutamina, o esfor&#231;o isom&#233;trico m&#225;ximo e/ou atropina podem ser adicionados para aumentar a sensibilidade do EED, particularmente nos pacientes em uso de betabloqueadores, bloqueador de canal de c&#225;lcio ou nitratos e naqueles com doen&#231;a uniarterial.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B41">41</xref>,<xref ref-type="bibr" rid="B42">42</xref></sup> Deve-se ter cuidado ao classificar o exame como subm&#225;ximo quando o paciente atinge 85% da frequ&#234;ncia card&#237;aca m&#225;xima prevista para a idade. Essa frequ&#234;ncia corresponde &#224; FC alvo, sendo, portanto, suficiente para caracterizar um exame conclusivo, e n&#227;o subm&#225;ximo ou inconclusivo.</p>
        <p>A atropina &#233; administrada em doses de 0,25 a 0,50 mg em intervalos de 0,5 a 1 minuto, conforme necess&#225;rio para atingir a FC alvo, at&#233; um total de 2,0 mg. Para evitar efeitos colaterais, a dose de 0,25 mg &#233; sugerida para pacientes idosos, com pequena superf&#237;cie corporal, neuropatas ou que est&#227;o pr&#243;ximos da FC alvo. A administra&#231;&#227;o de atropina na dose mais precoce de dobutamina (20 ou 30 mcg/kg/min) facilita o alcance precoce com menos efeitos colaterais, menor dose acumulada de dobutamina e menor tempo. A suspens&#227;o dos betabloqueadores facilita o alcance da FC alvo, e a n&#227;o suspens&#227;o adequada dos mesmos pode levar &#224; epis&#243;dios de hipertens&#227;o ou arritmia<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B41">41</xref></sup> no pico de dobutamina devido ao desbloqueio s&#250;bito dos receptores beta-adren&#233;rgicos.</p>
        <p>Betabloqueadores podem ser administrados para reverter os efeitos da dobutamina (principal utiliza&#231;&#227;o), mas tamb&#233;m para aumentar a sensibilidade do exame para a doen&#231;a univascular quando aplicados no pico de estresse, na vig&#234;ncia da dobutamina e de modo r&#225;pido.<sup><xref ref-type="bibr" rid="B42">42</xref></sup></p>
        <p>Os pacientes podem desenvolver arritmias menores, ou mais significativas, como fibrila&#231;&#227;o atrial e/ou taquicardia ventricular n&#227;o sustentada, que geralmente desaparecem ap&#243;s a interrup&#231;&#227;o da infus&#227;o de dobutamina. Nesses casos, devem ser administrados betabloqueadores. Em caso de taquicardia ventricular sustentada, a primeira considera&#231;&#227;o deve ser uma isquemia mioc&#225;rdica.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
        <p>Os medicamentos usados na EED, assim como suas doses e efeitos colaterais, se encontram na <xref ref-type="table" rid="t4">Tabela 5.3</xref>.</p>
        <table-wrap id="t4">
          <label>Tabela 5.3</label>
          <caption>
            <title>Drogas endovenosas usadas durante o teste de ecocardiografia de estresse, efeito colateral e contraindica&#231;&#245;es<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B12">12</xref>,<xref ref-type="bibr" rid="B35">35</xref>-<xref ref-type="bibr" rid="B43">43</xref></sup></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="middle">Dobutamina</td>
                <td align="center" valign="middle">Dose de 5 a 40 mcg/kg/min com aumento progressivo a cada 3 minutos.<break/> Efeitos colaterais: n&#225;usea, tremor, palpita&#231;&#227;o, cefaleia, hipotens&#227;o, hipertens&#227;o arterial, dor precordial, arritmia.<break/> As contraindica&#231;&#245;es se encontram na Tabela 5.4.</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">Atropina</td>
                <td align="center" valign="middle">Dose de at&#233; 2 mg iniciando na dose de 20 ou 30 mcg de dobutamina (protocolo precoce), caso n&#227;o esteja indicada a interrup&#231;&#227;o do teste.<break/> Efeitos colaterais: taquicardia, palpita&#231;&#227;o, boca seca, midr&#237;ase, n&#225;usea, agita&#231;&#227;o, reten&#231;&#227;o urin&#225;ria, aumento da press&#227;o intraocular.<break/> Contraindica&#231;&#227;o: glaucoma de &#226;ngulo fechado, hipertrofia de pr&#243;stata com reten&#231;&#227;o urin&#225;ria.</td>
              </tr>
              <tr>
                <td align="left" valign="middle">Metoprolol</td>
                <td align="center" valign="middle">Dose de 1 mg a 10 mg<break/> Efeitos colaterais: bradicardia, hipotens&#227;o arterial, tontura, cefaleia.<break/> Contraindica&#231;&#245;es: asma br&#244;nquica, doen&#231;a pulmonar grave, s&#237;ndrome bradi-taqui, bloqueio atrioventricular</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <p>As contraindica&#231;&#245;es absolutas e relativas para a dobutamina est&#227;o resumidas na <xref ref-type="table" rid="t5">Tabela 5.4</xref>.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
        <table-wrap id="t5">
          <label>Tabela 5.4</label>
          <caption>
            <title>Contraindica&#231;&#245;es da ecocardiografia de estresse farmacol&#243;gico com dobutamina na isquemia mioc&#225;rdica<sup><xref ref-type="bibr" rid="B38">38</xref>,<xref ref-type="bibr" rid="B39">39</xref>,<xref ref-type="bibr" rid="B43">43</xref></sup></title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="100%">
              <col/>
            </colgroup>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr style="background-color:#76B4CF">
                <td align="left" valign="middle">
                  <bold>Contraindica&#231;&#245;es absolutas</bold>
                </td>
              </tr>
              <tr>
                <td align="left" valign="middle">1) Infarto agudo do mioc&#225;rdio at&#233; 3-5 dias.</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">2) Angina inst&#225;vel.</td>
              </tr>
              <tr>
                <td align="left" valign="middle">3) Arritmia n&#227;o controlada com sintomas e instabilidade.</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">4) Estenose valvar a&#243;rtica grave sintom&#225;tica.</td>
              </tr>
              <tr>
                <td align="left" valign="middle">5) Miocardite, pericardite aguda</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">6) Hipertens&#227;o arterial grave (PA &gt; 200/110 mmHg) em repouso.</td>
              </tr>
              <tr>
                <td align="left" valign="middle">7) Endocardite ativa.</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">8) Tromboembolismo pulmonar ou infarto pulmonar.</td>
              </tr>
              <tr>
                <td align="left" valign="middle">9) Cardiomiopatia hipertr&#243;fica obstrutiva.</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td style="border-bottom: thin solid; border-color: #000000" align="left" valign="middle">10) Trombo ventricular recente ou m&#243;vel.</td>
              </tr>
              <tr style="background-color:#76B4CF">
                <td align="left" valign="middle">
                  <bold>Contraindica&#231;&#245;es relativas</bold>
                </td>
              </tr>
              <tr>
                <td align="left" valign="middle">1) Hipertireoidismo, anemia importante, AVC recente.</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">2) Aneurisma intracraniano ou de aorta tor&#225;cica (&gt;40 mm).</td>
              </tr>
              <tr>
                <td align="left" valign="middle">3) Estenose valvar a&#243;rtica moderada.</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN1">
              <p>AVC: acidente vascular cerebral; PA: press&#227;o arterial.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Todos os pacientes devem assinar o termo de consentimento informado antes do exame.</p>
        <p>Em rela&#231;&#227;o &#224; aquisi&#231;&#227;o da imagem, &#233; preciso tomar cuidado para que os cortes sejam feitos no mesmo plano e na mesma profundidade durante todo o exame para compara&#231;&#227;o mais confi&#225;vel no formato <italic>quad-screen</italic>.<sup><xref ref-type="bibr" rid="B38">38</xref></sup> Os ajustes devem ser realizados nas imagens basais de repouso e mantidos durante todo o exame.</p>
      </sec>
      <sec>
        <title>5.2. Tipo de Resposta Mioc&#225;rdica</title>
        <p>A EED normal &#233; definida pela presen&#231;a de movimento normal da parede regional e global em repouso, hipercinesia regional e global sob estresse e redu&#231;&#227;o importante no tamanho da cavidade do VE devido &#224; redu&#231;&#227;o da pr&#233; e p&#243;s-carga (fechamento fisiol&#243;gico da cavidade ventricular esquerda) (<xref ref-type="fig" rid="f6">Figura 5.1</xref>).</p>
        <fig id="f6">
          <label>Figura 5.1</label>
          <caption>
            <title>Ecocardiografia bidimensional &#8211; Ecocardiografia de estresse farmacol&#243;gico com dobutamina (EED) &#8211; resposta normal do ventr&#237;culo esquerdo: redu&#231;&#227;o da cavidade ventricular esquerda e hipercinesia de todas as paredes.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>A resposta isqu&#234;mica &#233; definida pelo desenvolvimento de uma nova ou piora da anormalidade no movimento-espessamento da parede sob estresse em ao menos um segmento mioc&#225;rdico (<xref ref-type="fig" rid="f7">Figura 5.2</xref>).</p>
        <fig id="f7">
          <label>Figura 5.2</label>
          <caption>
            <title>Ecocardiografia bidimensional &#8211; Ecocardiografia de estresse farmacol&#243;gico com dobutamina (EED) &#8211; isquemia lateral e septo com dilata&#231;&#227;o do ventr&#237;culo esquerdo (VE).</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>A isquemia mioc&#225;rdica pode ser causada por doen&#231;a dos vasos epic&#225;rdicos ou por outro motivo, como doen&#231;a microvascular, resposta hipertensiva ao estresse ou cardiomiopatia subjacente.</p>
        <p>Uma anormalidade grave do movimento-espessamento da parede em repouso, como acinesia, sem altera&#231;&#227;o com o estresse &#233; considerada uma resposta fixa e representa uma regi&#227;o infartada transmuralmente ou com uma borda de viabilidade epic&#225;rdica limitada. &#201; preciso ressaltar que a acinesia de repouso que se transforma em discinesia ao estresse &#233; considerada representativa de uma resposta mec&#226;nica de um segmento infartado ou reflexo do aumento da press&#227;o intraventricular e n&#227;o uma isquemia.</p>
        <p>A presen&#231;a de aneurisma deve ser registrada, dadas as implica&#231;&#245;es progn&#243;sticas e terap&#234;uticas.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
        <p>As diferen&#231;as entre a resposta mioc&#225;rdica segmentar e a global ao estresse na EED s&#227;o apresentadas na <xref ref-type="table" rid="t6">Tabela 5.5</xref>.</p>
        <table-wrap id="t6">
          <label>Tabela 5.5</label>
          <caption>
            <title>Tipo de resposta a ecocardiografia de estresse farmacol&#243;gico com dobutamina em compara&#231;&#227;o com repouso e dose baixa</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="100%">
              <col/>
            </colgroup>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle"><bold>Resposta normal segmentar:</bold> hipercinesia e aumento da for&#231;a de contra&#231;&#227;o.</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle"><bold>Resposta isqu&#234;mica segmentar:</bold> hipocinesia e diminui&#231;&#227;o da for&#231;a de contra&#231;&#227;o.</td>
              </tr>
              <tr>
                <td align="left" valign="middle"><bold>Resposta normal global:</bold> diminui&#231;&#227;o do volume diast&#243;lico e sist&#243;lico finais e aumento acentuado da fra&#231;&#227;o de eje&#231;&#227;o.</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle"><bold>Resposta isqu&#234;mica global:</bold> diminui&#231;&#227;o da fra&#231;&#227;o de eje&#231;&#227;o e dilata&#231;&#227;o da cavidade ventricular.</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <p>A EED deve ser interrompida quando: (1) atingir a FC alvo; (2) houver detec&#231;&#227;o de altera&#231;&#227;o segmentar da contratilidade de pelo menos dois segmentos; (3) ocorrer sintoma limitante ou arritmia complexa; (4) houver hipotens&#227;o ou hipertens&#227;o arterial importante (PAS &#8805; 220-240 mmHg e/ou PA diast&#243;lica [PAD] &#8805; 120 mmHg); (5) o fim do protocolo for atingido. O uso de ARUS ou contraste para ultrassom deve ser considerado para melhorar a defini&#231;&#227;o do endoc&#225;rdio na aus&#234;ncia de boa visibilidade em repouso ao corte apical de dois ou mais segmentos cont&#237;guos.</p>
        <p>Os efeitos colaterais mais observados na EED s&#227;o sensa&#231;&#227;o de calor, n&#225;usea, arrepio, urg&#234;ncia urin&#225;ria, palpita&#231;&#245;es relacionadas &#224; taquicardia e, raramente, leve cefaleia.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> A cefaleia mais acentuada na vig&#234;ncia de dobutamina deve levantar a suspeita de hipertens&#227;o arterial sist&#234;mica.</p>
        <p>A interpreta&#231;&#227;o e a conclus&#227;o do teste na isquemia se encontram na <xref ref-type="table" rid="t7">Tabela 5.6</xref>.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
        <table-wrap id="t7">
          <label>Tabela 5.6</label>
          <caption>
            <title>Interpreta&#231;&#227;o do espessamento segmentar no resultado da ecocardiografia de estresse farmacol&#243;gico com dobutamina na pesquisa da isquemia mioc&#225;rdica</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="100%">
              <col/>
            </colgroup>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle">1. Repouso = normal Estresse = hipercinesia Conclus&#227;o = normal</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">2. Repouso = normal ou hipocinesia Estresse = hipocinesia ou acinesia Conclus&#227;o = isquemia</td>
              </tr>
              <tr>
                <td align="left" valign="middle">3. Repouso = acinesia Estresse = melhora em baixa dose e piora em alta dose Conclus&#227;o = viabilidade e isquemia</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">4. Repouso = acinesia Estresse = acinesia ou discinesia Conclus&#227;o = cicatriz/fibrose</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <p>Os dados absolutos e relativos para a conclus&#227;o do teste se encontram na <xref ref-type="table" rid="t8">Tabela 5.7</xref>.</p>
        <table-wrap id="t8">
          <label>Tabela 5.7</label>
          <caption>
            <title>Dados absolutos e relativos para conclus&#227;o da ecocardiografia de estresse</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="100%">
              <col/>
            </colgroup>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle">1- Atingir 85% da frequ&#234;ncia card&#237;aca (FC) m&#225;xima prevista para a idade (220 &#8211; idade).<break/> 2- Dose m&#225;xima de drogas usadas (fim do protocolo) ou sintomas limitantes.<break/> 3- Sinais ecocardiogr&#225;ficos de isquemia mioc&#225;rdica (independente de qualquer outro fator).<break/> 4- Taquicardia ventricular sustentada / arritmias complexas.<break/> 5- Queda sintom&#225;tica da PA ou da FC (PAS &gt; 20 mmHg).</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">Dados relativos para conclus&#227;o da ecocardiografia de estresse:<break/> 1- Piora da contratilidade em novos segmentos (um ou mais) ou segmentos j&#225; alterados em repouso.<break/> 2- Dilata&#231;&#227;o do ventr&#237;culo esquerdo.<break/> 3- In&#237;cio de arritmia (fibrila&#231;&#227;o atrial, taquicardia supraventricular, arritmia ventricular complexa).</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN2">
              <p>FC: frequ&#234;ncia card&#237;aca; PA: press&#227;o arterial; PAS: press&#227;o arterial sist&#243;lica.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Diversos estudos demonstram a excelente acur&#225;cia da EED usando a arteriografia coronariana como padr&#227;o ouro para compara&#231;&#227;o. Para a detec&#231;&#227;o de doen&#231;a arterial (DA), a EED tem sensibilidade semelhante &#224; imagem tomogr&#225;fica de perfus&#227;o nuclear, com maior especificidade. A EED tem maior sensibilidade para detec&#231;&#227;o de les&#227;o na art&#233;ria descendente anterior e de tronco principal esquerdo ou multiarterial.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
        <p>Se n&#227;o for detectada isquemia e o estresse for inadequado, seja por janela ac&#250;stica limitada ou por n&#227;o se atingir a frequ&#234;ncia card&#237;aca alvo, o resultado do exame pode ser falso negativo.</p>
        <p>Pacientes com resultados de ecocardiografia de estresse falso-positivos s&#227;o semelhantes &#224;queles com resultados verdadeiro-positivos. Ambos devem receber manejo intensivo dos fatores de risco e acompanhamento cuidadoso.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
        <p>Deve constar do relat&#243;rio como conclus&#227;o do exame:</p>
        <p>Normal, isquemia, aus&#234;ncia de espessamento da parede (fibrose) ou combina&#231;&#227;o desses achados, desde que obtido o <italic>endpoint</italic> adequado. Caso nada tenha ocorrido ao final do protocolo e a frequ&#234;ncia alvo n&#227;o tenha sido atingida, o teste pode ser descrito como inconclusivo, ou mesmo como negativo at&#233; a FC atingida. Nesse &#250;ltimo caso, por&#233;m, &#233; importante ressaltar que a sensibilidade do mesmo se encontra reduzida para diagn&#243;stico de isquemia mioc&#225;rdica induzida por n&#227;o ter atingido a FC alvo.</p>
        <p>Para a interpreta&#231;&#227;o das imagens, s&#227;o comparados o tamanho, a forma e a fun&#231;&#227;o do VE em cada etapa nos quatro cortes simult&#226;neos e em cada corte nas etapas simult&#226;neas. Essas imagens devem ser obtidas na mesma posi&#231;&#227;o em cada est&#225;gio. Na resposta normal sob estresse, o VE &#233; menor do que em repouso, a forma &#233; mantida e aumenta a excurs&#227;o do endoc&#225;rdio, com consequente aumento da espessura mioc&#225;rdica.<sup><xref ref-type="bibr" rid="B43">43</xref></sup></p>
        <p>A dilata&#231;&#227;o e redu&#231;&#227;o da fra&#231;&#227;o de eje&#231;&#227;o do VE (FEVE) durante a EED geralmente &#233; indicativa de isquemia extensa.</p>
        <p>Cada segmento &#233; pontuado de acordo com os seguintes crit&#233;rios:</p>
        <list list-type="order">
          <list-item>
            <p>Movimento normal da parede (espessamento mioc&#225;rdico &gt;50%);</p>
          </list-item>
          <list-item>
            <p>Hipocinesia (espessamento mioc&#225;rdico de 10 a 50%);</p>
          </list-item>
          <list-item>
            <p>Acinesia ou hipocinesia grave (espessamento mioc&#225;rdico &lt;10%);</p>
          </list-item>
          <list-item>
            <p>Discinesia (movimento sist&#243;lico paradoxal e movimento sist&#243;lico abaulado para fora).</p>
          </list-item>
        </list>
        <p>O escore de motilidade parietal (WMSI, do ingl&#234;s <italic>wall motion score index</italic>) &#233; calculado pela divis&#227;o da soma de todos os escores segmentares pelo n&#250;mero total de segmentos mioc&#225;rdicos (16 ou 17, com &#225;pice do VE inclu&#237;do). No mioc&#225;rdio normal e n&#227;o isqu&#234;mico, o &#237;ndice &#233; igual a 1.<sup><xref ref-type="bibr" rid="B39">39</xref></sup> Os cortes ecocardiogr&#225;ficos que devem ser obtidos e a correspondente irriga&#231;&#227;o coronariana est&#227;o demonstrados na <xref ref-type="table" rid="t9">Tabela 5.8</xref>.</p>
        <table-wrap id="t9">
          <label>Tabela 5.8</label>
          <caption>
            <title>Avalia&#231;&#227;o ecocardiogr&#225;fica dos segmentos e irriga&#231;&#227;o coron&#225;ria</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 style="background-color:#76B4CF">
                <th align="left" valign="middle">CORTE</th>
                <th align="center" valign="middle">IRRIGA&#199;&#195;O CORONARIANA</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle">Paraestenal longitudinal ou Apical 3C</td>
                <td align="center" valign="middle">ADA, ACD e ACX</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">Apical 4C</td>
                <td align="center" valign="middle">ADA, ACD e ACX</td>
              </tr>
              <tr>
                <td align="left" valign="middle">Apical 2C</td>
                <td align="center" valign="middle">ADA, ACD</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">Paraesternal transversal</td>
                <td align="center" valign="middle">ADA, ACD e ACX</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN3">
              <p>ADA: art&#233;ria descendente anterior; ACD: art&#233;ria coron&#225;ria direita; ACX: art&#233;ria circunflexa.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Uma dificuldade para interpretar o exame &#233; que portadores de marca-passo podem ter resposta de frequ&#234;ncia inadequada e tamb&#233;m podem apresentar anormalidades regionais da parede devido ao efeito de estimula&#231;&#227;o. Por esse motivo, a dobutamina muitas vezes n&#227;o consegue fornecer as respostas adequadas a esses pacientes.</p>
        <p>Em rela&#231;&#227;o &#224; estratifica&#231;&#227;o de risco e progn&#243;stico, a EED geralmente &#233; utilizada para o diagn&#243;stico de DAC com isquemia, risco de eventos card&#237;acos e progn&#243;stico. A estratifica&#231;&#227;o de risco com a EED normal est&#225; associada a um progn&#243;stico benigno e &#233; semelhante ou superior a imagem de tomografia computadorizada por emiss&#227;o de f&#243;ton &#250;nico (SPECT, do ingl&#234;s <italic>single-photon emission computed tomography</italic>) mioc&#225;rdica normal (t&#225;lio-201, tecn&#233;cio-99 ou sestamibi).</p>
        <p>Quando comparamos os pacientes submetidos a ecocardiografia de estresse de esfor&#231;o, aqueles submetidos a EED geralmente s&#227;o mais velhos, t&#234;m mais comorbilidades e neles o movimento da parede e a FE foram identificados na an&#225;lise multivariada como os melhores preditores de eventos card&#237;acos.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
        <p>Os dados que devem constar do relat&#243;rio da EED se encontram na <xref ref-type="table" rid="t10">Tabela 5.9</xref>.<sup><xref ref-type="bibr" rid="B38">38</xref></sup> O segmento basal inferior e apical devem ser avaliados em m&#250;ltiplas imagens para evitar um resultado falso positivo para isquemia.</p>
        <table-wrap id="t10">
          <label>Tabela 5.9</label>
          <caption>
            <title>Recomenda&#231;&#245;es para relato/laudo dos resultados da ecocardiografia de estresse farmacol&#243;gico com dobutamina<sup><xref ref-type="bibr" rid="B38">38</xref>,<xref ref-type="bibr" rid="B39">39</xref>,<xref ref-type="bibr" rid="B43">43</xref></sup></title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="100%">
              <col/>
            </colgroup>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle">Informa&#231;&#245;es cl&#237;nicas e indica&#231;&#227;o do estudo.</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle"><bold>Repouso:</bold> Avalia&#231;&#227;o regional do espessamento de parede.</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">Motilidade parietal: N&#250;mero, localiza&#231;&#227;o e grau de altera&#231;&#245;es regionais (ou global).</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">2- Estimativa da fra&#231;&#227;o de eje&#231;&#227;o.</td>
              </tr>
              <tr>
                <td align="left" valign="middle"><bold>Estresse:</bold> Avalia&#231;&#227;o regional do espessamento da parede.</td>
              </tr>
              <tr>
                <td align="left" valign="middle">1- Motilidade parietal: N&#250;mero, localiza&#231;&#227;o e grau de altera&#231;&#245;es regionais (ou global). 2- Estimativa da fra&#231;&#227;o de eje&#231;&#227;o.</td>
              </tr>
              <tr>
                <td align="left" valign="middle">3- A avalia&#231;&#227;o da contratilidade segmentar deve ser repetida quantas vezes forem necess&#225;rias.</td>
              </tr>
              <tr>
                <td align="left" valign="middle">4- Se houver uso de agente de realce ultrassonogr&#225;fico (contraste), informar o agente e dose administrados.</td>
              </tr>
              <tr>
                <td align="left" valign="middle">Dados do protocolo utilizado:</td>
              </tr>
              <tr>
                <td align="left" valign="middle">1- Doses do(s) agente(s) para estresse farmacol&#243;gico.</td>
              </tr>
              <tr>
                <td align="left" valign="middle">2- Se a FC alvo foi alcan&#231;ada. FC e PA em cada est&#225;gio.</td>
              </tr>
              <tr>
                <td align="left" valign="middle">3- Achados cl&#237;nicos e de ECG durante o estudo do repouso e do estresse.</td>
              </tr>
              <tr>
                <td align="left" valign="middle">4- Achados ecocardiogr&#225;ficos p&#243;s-teste.</td>
              </tr>
              <tr>
                <td align="left" valign="middle">5- Motivo do t&#233;rmino do exame (conclus&#227;o do protocolo, isquemia, sintomas ou complica&#231;&#245;es).</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN4">
              <p>FC: frequ&#234;ncia card&#237;aca; ECG: eletrocardiograma; PA: press&#227;o arterial.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>5.3. Avalia&#231;&#227;o Durante a Ecocardiografia de Estresse Farmacol&#243;gico com Dobutamina e na Recupera&#231;&#227;o</title>
        <p>O desenvolvimento de anormalidades na motilidade parietal durante os est&#225;gios iniciais do estresse indica a presen&#231;a de obstru&#231;&#227;o coronariana grave com pouca ou nenhuma reserva de perfus&#227;o mioc&#225;rdica. Na dose baixa, na presen&#231;a de obstru&#231;&#227;o coronariana moderada, com alguma preserva&#231;&#227;o da reserva de perfus&#227;o, o aumento do fluxo sangu&#237;neo acarreta aumento do espessamento e da motilidade parietal. Na dose alta, a combina&#231;&#227;o de taquicardia e obstru&#231;&#227;o coronariana resulta em decl&#237;nio acentuado do fluxo subendoc&#225;rdico, com diminui&#231;&#227;o correspondente na fun&#231;&#227;o regional.</p>
        <p>A persist&#234;ncia de anormalidades na motilidade parietal no per&#237;odo de recupera&#231;&#227;o pode ser consequ&#234;ncia do atordoamento e &#233; um indicador de isquemia mais grave. Imagens de recupera&#231;&#227;o isqu&#234;mica tardia devem ser consideradas em pacientes com anormalidades graves e extensas do espessamento da parede induzidas por estresse. A maioria dos pacientes com resultados anormais na EED e submetidos &#224; angiografia coron&#225;ria apresenta DAC obstrutiva.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
        <p>A hipoperfus&#227;o induzida por estresse reflete a &#225;rea do mioc&#225;rdio em risco e a gravidade reflete a magnitude da anormalidade da motilidade parietal, e ambas est&#227;o exponencialmente correlacionadas com um aumento nos eventos adversos cardiovasculares.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
      </sec>
      <sec>
        <title>5.4. Dilata&#231;&#227;o Isqu&#234;mica Transit&#243;ria do Ventr&#237;culo Esquerdo</title>
        <p>Pacientes com ecocardiograma de estresse anormal e dilata&#231;&#227;o isqu&#234;mica transit&#243;ria apresentam maior percentagem de doen&#231;a multiarterial e taxa mais elevada de eventos adversos.</p>
        <p>A EED pode ser utilizada para detec&#231;&#227;o de isquemia e estratifica&#231;&#227;o de risco em pacientes com bloqueio de ramo esquerdo (BRE)<sup><xref ref-type="bibr" rid="B3">3</xref></sup> (<xref ref-type="fig" rid="f8">Figura 5.3</xref>).</p>
        <fig id="f8">
          <label>Figura 5.3</label>
          <caption>
            <title>Ecocardiografia bidimensional &#8211; bloqueio de ramo esquerdo - eixo longitudinal: repouso &#8211; septo normal; EED/pico &#8211; septo pouco an&#244;malo; ecocardiografia de estresse farmacol&#243;gico com dobutamina (EED)/p&#243;s-imediato (POS) &#8211; septo muito an&#244;malo.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>Em pacientes com BRE submetidos a EED e a coronariografia (Cine), Yanik et al.<sup><xref ref-type="bibr" rid="B44">44</xref></sup> observaram boa sensibilidade, especificidade e acur&#225;cia da EED para identifica&#231;&#227;o de isquemia no territ&#243;rio da art&#233;ria descendente anterior (ADA) de 82%, 95% e 90%, nos territ&#243;rios da art&#233;ria circunflexa e coron&#225;ria direita de 88%, 96% e 93%. Em estudo semelhante com EED, tomografia de perfus&#227;o mioc&#225;rdica e Cine, Mairesse et al.<sup><xref ref-type="bibr" rid="B45">45</xref></sup> observaram que a EED teve bom desempenho na detec&#231;&#227;o de isquemia no territ&#243;rio da ADA, com sensibilidade de 83%, especificidade de 92% e acur&#225;cia de 87%.</p>
        <p>Os pacientes idosos t&#234;m a indica&#231;&#227;o de EED (estresse farmacol&#243;gico em geral) como primeira op&#231;&#227;o, assim como pacientes com problemas ortop&#233;dicos ou neurol&#243;gicos que n&#227;o conseguem realizar o teste de esfor&#231;o.<sup><xref ref-type="bibr" rid="B46">46</xref></sup> Se a FC desejada n&#227;o for alcan&#231;ada, indica-se atropina e o esfor&#231;o isom&#233;trico concomitantemente, com metade da for&#231;a m&#225;xima por 3 a 4 minutos,<sup><xref ref-type="bibr" rid="B47">47</xref></sup> mantendo a boca aberta e abdome relaxado para evitar a manobra vagal.</p>
      </sec>
      <sec>
        <title>5.5. Compara&#231;&#227;o com Outras Modalidades de Imagem</title>
        <p>Grandes estudos e meta-an&#225;lises compararam o valor preditivo da EED e do SPECT em diferentes pacientes. O estudo PROMISE comparou imagens anat&#244;micas usando angiotomografia com imagens funcionais em 10.003 pacientes est&#225;veis com sintomas sugestivos de DAC. Contudo, realizou-se SPECT de estresse ou EED em apenas 1.083 pacientes. Nenhum desses estudos que compararam a EED com outras modalidades considerou o valor incremental dos achados auxiliares detectados por imagens ecocardiogr&#225;ficas realizadas no momento da ecocardiografia de estresse, incluindo detec&#231;&#227;o de causas n&#227;o isqu&#234;micas de sintomas card&#237;acos.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
        <p>A EED tem precis&#227;o diagn&#243;stica e progn&#243;stica semelhante &#224; imagem de perfus&#227;o sob estresse com radionucl&#237;deos ou resson&#226;ncia magn&#233;tica.</p>
      </sec>
      <sec>
        <title>5.6. Valor da Ecocardiografia de Estresse Farmacol&#243;gico com Dobutamina Negativa</title>
        <p>Samiei et al.<sup><xref ref-type="bibr" rid="B48">48</xref></sup> estudaram 705 pacientes sem hist&#243;ria pr&#233;via de DAC e ecocardiografia de estresse de esfor&#231;o ou EED negativas. Em seu estudo, os pacientes que tiveram eventos eram mais velhos, diab&#233;ticos ou hipertensos, e os resultados devem ser interpretados com mais cautela, dado o menor valor preditivo negativo da EED nesses pacientes. Al&#233;m disso, a precis&#227;o diagn&#243;stica pode ser significativamente afetada pelo uso de betabloqueadores, resultando em teste falso negativo.<sup><xref ref-type="bibr" rid="B43">43</xref>,<xref ref-type="bibr" rid="B49">49</xref></sup></p>
      </sec>
      <sec>
        <title>5.7. Complica&#231;&#245;es da Ecocardiografia de Estresse Farmacol&#243;gico com Dobutamina</title>
        <p>Complica&#231;&#245;es ocorrem em &lt; 0,1% dos pacientes (meta-an&#225;lise de 26 estudos). A mais comum &#233; a arritmia na isquemia importante e na FE &lt; 35%. Fibrila&#231;&#227;o atrial e arritmias ventriculares n&#227;o sustentadas ocorrem em cerca de 3% dos pacientes. Contra&#231;&#245;es atriais ou ventriculares prematuras frequentes ocorrem em cerca de 10%. A taquicardia ventricular sustentada &#233; rara.<sup><xref ref-type="bibr" rid="B43">43</xref></sup> Pode ocorrer angina, hipotens&#227;o e obstru&#231;&#227;o da regi&#227;o m&#233;dioventricular e da VSVE (esta pode levar a dor tor&#225;cica e hipotens&#227;o arterial). Apesar da seguran&#231;a, aproximadamente 50% dos pacientes relatam alguma rea&#231;&#227;o: n&#225;usea, rubor, cefaleia, pesco&#231;o ou peito batendo, parestesia, urg&#234;ncia urin&#225;ria, dispneia ou boca seca.<sup><xref ref-type="bibr" rid="B38">38</xref></sup></p>
        <p>A <xref ref-type="fig" rid="f9">Figura 5.4</xref> mostra a um ecocardiograma com dobutamina, adicionando a t&#233;cnica tridimensional, positivo para isquemia mioc&#225;rdica induzida em regi&#227;o septal.</p>
        <fig id="f9">
          <label>Figura 5.4</label>
          <caption>
            <title>Ecocardiografia tridimensional (ECO 3D) &#8211; eixo menor &#8211; repouso &#8211; septo normal. ECO 3D &#8211; eixo menor &#8211; ecocardiografia de estresse farmacol&#243;gico com dobutamina (EED) pico &#8211; septo acin&#233;tico.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
      </sec>
    </sec>
    <sec>
      <title>6. Ecocardiografia de Estresse com Dipiridamol</title>
      <p>O dipiridamol &#233; um estressor mioc&#225;rdico farmacol&#243;gico que provoca ac&#250;mulo de adenosina end&#243;gena por meio do est&#237;mulo de seus receptores A2 nas arter&#237;olas coronarianas.<sup><xref ref-type="bibr" rid="B50">50</xref></sup> O f&#225;rmaco determina o aumento do fluxo sangu&#237;neo coronariano e do fluxo sangu&#237;neo mioc&#225;rdico em at&#233; 4 a 5 vezes em rela&#231;&#227;o ao basal, sem aumentar significativamente a FC e o volume sist&#243;lico e causando queda da PAS.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Assim, na presen&#231;a de uma estenose epic&#225;rdica cr&#237;tica ou disfun&#231;&#227;o microcirculat&#243;ria, sua administra&#231;&#227;o resulta em heterogeneidade do fluxo sangu&#237;neo coron&#225;rio entre segmentos comprometidos por estenoses e art&#233;rias coron&#225;rias normais.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Ocorre uma incompatibilidade entre oferta e demanda, o que leva a uma diminui&#231;&#227;o do fluxo subendoc&#225;rdico em &#225;reas de estenose arterial por meio de fen&#244;menos de roubo de fluxo.<sup><xref ref-type="bibr" rid="B51">51</xref></sup></p>
      <p>As indica&#231;&#245;es, tipos de equipamentos, preparo do paciente, etapas do procedimento, aquisi&#231;&#227;o de imagens, consentimento informado e tipos de resposta mioc&#225;rdica s&#227;o similares &#224;queles descritos para a dobutamina.</p>
      <sec>
        <title>6.1. Protocolos</title>
        <p>H&#225; dois protocolos padr&#227;o para a administra&#231;&#227;o de dipiridamol:</p>
        <list list-type="order">
          <list-item>
            <p>
              <bold>Protocolo escalonado:</bold>
            </p>
            <p>Infus&#227;o intravenosa de 0,84 mg/kg durante 10 min, em duas infus&#245;es separadas, sendo 0,56 mg/kg durante 4 min, seguida de 4 min de observa&#231;&#227;o sem medica&#231;&#227;o e, se ainda negativo o teste, 0,28 mg/kg adicionais em mais 2 minutos. Se nenhum <italic>endpoint</italic> (no caso, isquemia) for alcan&#231;ado, adiciona-se 0,25 mg de atropina a cada minuto, totalizando o m&#225;ximo de 1 mg neste tipo de teste (<xref ref-type="fig" rid="f10">Figura 6.1</xref>).</p>
          </list-item>
          <list-item>
            <p>
              <bold>Protocolo acelerado:</bold>
            </p>
            <p>Infus&#227;o intravenosa da dose global de 0,84 mg/kg em 6 minutos, seguida de um per&#237;odo de observa&#231;&#227;o de 4 minutos sem medica&#231;&#227;o, n&#227;o sendo necess&#225;rio a administra&#231;&#227;o de atropina ao final do teste (<xref ref-type="fig" rid="f11">Figura 6.2</xref>).</p>
            <p>Em ambos os protocolos, deve-se disponibilizar aminofilina para uso imediato caso ocorra um evento adverso relacionado ao dipiridamol, que deve ser infundida rotineiramente ao final do teste, independentemente do resultado,<sup><xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B50">50</xref></sup> devido &#224; meia-vida mais longa do dipiridamol.</p>
            <p>O dipiridamol atua pela inibi&#231;&#227;o da recapta&#231;&#227;o da adenosina end&#243;gena. A meia-vida do dipiridamol alfa (ou seja, o decl&#237;nio inicial ap&#243;s o pico de concentra&#231;&#227;o) &#233; de aproximadamente 30 a 45 minutos. A meia-vida beta (o decl&#237;nio terminal na concentra&#231;&#227;o plasm&#225;tica) &#233; de aproximadamente 10 horas. O dipiridamol &#233; metabolizado no f&#237;gado em conjugado de &#225;cido glucur&#244;nico e excretado na bile.<sup><xref ref-type="bibr" rid="B52">52</xref>,<xref ref-type="bibr" rid="B53">53</xref></sup> Seu efeito vasodilatador pode causar uma queda na PA e uma leve eleva&#231;&#227;o na FC.</p>
          </list-item>
        </list>
        <fig id="f10">
          <label>Figura 6.1</label>
          <caption>
            <title>Protocolo dipiridamol-atropina alta dose escalonado.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <fig id="f11">
          <label>Figura 6.2</label>
          <caption>
            <title>Protocolo dipiridamol alta dose acelerado.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
      </sec>
      <sec>
        <title>6.2. Efeitos Colaterais</title>
        <p>Os principais efeitos colaterais do dipiridamol incluem a incid&#234;ncia de bloqueio atrioventricular (BAV), que pode chegar a BAV total, por&#233;m em menor grau que aquele observada com adenosina (2%); dor tor&#225;cica em cerca de 20% dos pacientes, inespec&#237;fica e n&#227;o necessariamente indicativa da presen&#231;a de DAC; e efeitos colaterais menores, incluindo cefaleia, tontura, n&#225;useas, hipotens&#227;o e rubor.<sup><xref ref-type="bibr" rid="B52">52</xref></sup></p>
      </sec>
      <sec>
        <title>6.3. Contraindica&#231;&#245;es</title>
        <p>As principais contraindica&#231;&#245;es ao uso de dipiridamol (<xref ref-type="table" rid="t11">Tabela 6.1</xref>) incluem: pacientes com doen&#231;a pulmonar broncoesp&#225;stica com sibil&#226;ncia cont&#237;nua ou hist&#243;ria de doen&#231;a reativa significativa das vias a&#233;reas, hipertens&#227;o n&#227;o controlada (PAS superior a 200 mmHg ou PAD superior a 110 mmHg), PAS inferior a 90 mmHg, hipersensibilidade conhecida ao dipiridamol, ingest&#227;o de cafe&#237;na nas &#250;ltimas 24 horas e BAV de segundo ou terceiro grau sem marca-passo funcional.<sup><xref ref-type="bibr" rid="B52">52</xref></sup> Entretanto, a presen&#231;a de angina inst&#225;vel ou s&#237;ndrome coronariana aguda complicada, arritmias card&#237;acas complexas, estenose valvar a&#243;rtica grave sintom&#225;tica e CMH com obstru&#231;&#227;o da VSVE tamb&#233;m impedem a realiza&#231;&#227;o de um teste estressor do mioc&#225;rdio, assim como nos demais protocolos.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
        <table-wrap id="t11">
          <label>Tabela 6.1</label>
          <caption>
            <title>Contraindica&#231;&#245;es para a ecocardiografia de estresse com dipiridamol</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 style="background-color:#76B4CF">
                <th align="center" valign="middle">Contraindica&#231;&#245;es para todos os protocolos</th>
                <th align="center" valign="middle">Contraindica&#231;&#245;es para ecocardiografia de estresse com dipiridamol</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="center" valign="middle">Angina pectoris inst&#225;vel</td>
                <td align="center" valign="middle">Doen&#231;a pulmonar broncoesp&#225;stica com sibil&#226;ncia cont&#237;nua</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="center" valign="middle">S&#237;ndrome coronariana aguda ou complicada</td>
                <td align="center" valign="middle">Hist&#243;ria de doen&#231;a reativa significativa das vias a&#233;reas</td>
              </tr>
              <tr>
                <td align="center" valign="middle">Arritmia card&#237;aca complexa<break/> ICC descompensada</td>
                <td align="center" valign="middle">BAV de segundo ou terceiro grau sem marca-passo funcional</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="center" valign="middle">Estenose a&#243;rtica grave sintom&#225;tica</td>
                <td align="center" valign="middle">Press&#227;o arterial sist&#243;lica inferior a 90 mmHg</td>
              </tr>
              <tr>
                <td align="center" valign="middle">CMH e obstru&#231;&#227;o na via de sa&#237;da do ventr&#237;culo esquerdo</td>
                <td align="center" valign="middle">Hipersensibilidade conhecida ao dipiridamol</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="center" valign="middle"/>
                <td align="center" valign="middle">Ingest&#227;o de cafe&#237;na nas &#250;ltimas 24 horas</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN5">
              <p>BAV: bloqueio atrioventricular; ICC: insufici&#234;ncia card&#237;aca congestiva.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>6.4. Reserva de Fluxo Coronariano</title>
        <p>O estresse farmacol&#243;gico com dipiridamol &#233; mais seguro, mais simples e o mais adequado para a avalia&#231;&#227;o combinada da RFC com movimento-espessamento parietal.<sup><xref ref-type="bibr" rid="B50">50</xref></sup> Entretanto, as caracter&#237;sticas individuais dos pacientes, o custo local do medicamento e as prefer&#234;ncias do examinador devem ser levadas em considera&#231;&#227;o na escolha de um teste em detrimento de outro. Por exemplo, em pacientes com hipertens&#227;o arterial sist&#234;mica grave e/ou hist&#243;ria de arritmias atriais ou ventriculares significativas, o teste com dipiridamol pode ser mais adequado.</p>
      </sec>
      <sec>
        <title>6.5. Acur&#225;cia</title>
        <p>A acur&#225;cia do estresse farmacol&#243;gico com dipiridamol (protocolo acelerado ou escalonado com atropina), quando comparado &#224; dobutamina-atropina, tem alta precis&#227;o diagn&#243;stica, semelhante &#224; da ecocardiografia de estresse m&#225;ximo em esteira p&#243;s-exerc&#237;cio, mas ao custo de uma sensibilidade menor, e especificidade maior. Al&#233;m disso, o teste de ecocardiografia de estresse com dipiridamol-atropina pode superar os efeitos da terapia concomitante com betabloqueadores, atingindo n&#237;veis elevados e valor diagn&#243;stico compar&#225;vel.<sup><xref ref-type="bibr" rid="B54">54</xref></sup> Contudo, o uso de betabloqueadores, por ter a&#231;&#227;o cardioprotetora, quando n&#227;o suspenso antes do exame, pode induzir tamb&#233;m aqui, a um resultado falso-negativo.</p>
        <p>Diversas meta-an&#225;lises compararam a precis&#227;o das imagens de perfus&#227;o com a ecocardiografia de estresse.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Esses testes obtiveram sensibilidades semelhantes para a detec&#231;&#227;o de DAC, mas a ecocardiografia de estresse apresentou maior especificidade. Para detec&#231;&#227;o de les&#227;o do tronco principal esquerdo ou DAC multiarterial, a ecocardiografia de estresse apresentou maior sensibilidade em compara&#231;&#227;o &#224; imagem de perfus&#227;o mioc&#225;rdica nuclear, que compara diferen&#231;as relativas na perfus&#227;o e pode n&#227;o detectar a isquemia equilibrada ou global.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B55">55</xref>-<xref ref-type="bibr" rid="B57">57</xref></sup></p>
      </sec>
    </sec>
    <sec>
      <title>7. Ecocardiografia de Estresse com Adenosina ou Regadenoson</title>
      <p>A adenosina &#233; uma purina presente em todos os tecidos corporais,<sup><xref ref-type="bibr" rid="B58">58</xref>,<xref ref-type="bibr" rid="B59">59</xref></sup> originada dos nucleot&#237;deos de adenina e da degrada&#231;&#227;o de ATP. &#201; metabolizada com a mesma facilidade com a qual &#233; gerada, tornando seus n&#237;veis corporais muito vari&#225;veis.<sup><xref ref-type="bibr" rid="B58">58</xref>,<xref ref-type="bibr" rid="B60">60</xref>,<xref ref-type="bibr" rid="B61">61</xref></sup> Sua a&#231;&#227;o &#233; mediada por meio de quatro receptores de membrana, os receptores de adenosina A1, A2A, A2B e A3.<sup><xref ref-type="bibr" rid="B58">58</xref>,<xref ref-type="bibr" rid="B59">59</xref>,<xref ref-type="bibr" rid="B62">62</xref></sup> Todos s&#227;o acoplados &#224; prote&#237;na G,<sup><xref ref-type="bibr" rid="B59">59</xref></sup> sendo que A1 e A3 se ligam &#224; prote&#237;na G inibit&#243;ria e os receptores A2 se ligam &#224; G estimulat&#243;ria.<sup><xref ref-type="bibr" rid="B59">59</xref>-<xref ref-type="bibr" rid="B61">61</xref></sup> Isso significa que recrutam diferentes vias mediante a liga&#231;&#227;o com a adenosina.<sup><xref ref-type="bibr" rid="B58">58</xref>-<xref ref-type="bibr" rid="B73">73</xref></sup> Os receptores de adenosina podem ent&#227;o ser divididos em dois subtipos principais: receptores A1 e A3, que inibem a adenilato ciclase, e receptores A2 estimulados pela enzima adenilato ciclase. Os receptores A1 predominam no mioc&#225;rdio, enquanto os receptores A2 s&#227;o encontrados nas art&#233;rias coron&#225;rias (c&#233;lulas endoteliais e musculares lisas). Portanto, a ativa&#231;&#227;o dos receptores A2A dilata as art&#233;rias coron&#225;rias, causando hiperemia e aumento da carga sangu&#237;nea coronariana. A ativa&#231;&#227;o dos receptores A2A na presen&#231;a de estenose coronariana cr&#237;tica desempenha um papel fundamental na vasodilata&#231;&#227;o inadequada e isquemia subendoc&#225;rdica para fen&#244;menos de roubo vertical e horizontal e anormalidade da motilidade segmentar regional. Essas a&#231;&#245;es tamb&#233;m est&#227;o presentes no teste com dipiridamol.</p>
      <p>A infus&#227;o intravenosa ou bolus intracoron&#225;rio de adenosina induz fluxo m&#225;ximo (hiperemia). Em condi&#231;&#245;es fisiol&#243;gicas, a art&#233;ria coron&#225;ria epic&#225;rdica apresenta fluxo laminar e gradiente de press&#227;o nulo ou baixo da parte proximal para a distal. A estenose coronariana induz acelera&#231;&#227;o do fluxo no local e pode diminuir a press&#227;o distal &#224;s les&#245;es em repouso, limitando a acelera&#231;&#227;o do fluxo da hiperemia e provocando uma diminui&#231;&#227;o adicional da press&#227;o p&#243;s-esten&#243;tica durante o estresse.<sup><xref ref-type="bibr" rid="B22">22</xref></sup></p>
      <p>Em condi&#231;&#245;es fisiol&#243;gicas normais, a perfus&#227;o mioc&#225;rdica &#233; autorregulada por pr&#233;-arter&#237;olas no epic&#225;rdio e arter&#237;olas no mioc&#225;rdio, de modo que o t&#244;nus microvascular contribui para a maior parte da resist&#234;ncia coronariana. Condi&#231;&#245;es microvasculares patol&#243;gicas, incluindo fibrose perivascular (hipertens&#227;o arterial,<sup><xref ref-type="bibr" rid="B64">64</xref></sup> DAC,<sup><xref ref-type="bibr" rid="B65">65</xref></sup> hipertrofia mioc&#225;rdica, diabetes mellitus, transplante card&#237;aco, etc.), podem provocar angina microvascular, aumentando o t&#244;nus microvascular em repouso e/ou limitando a vasodilata&#231;&#227;o no estresse.</p>
      <p>Portanto, o uso de vasodilatadores para induzir estresse parece justificado em testes funcionais n&#227;o invasivos. Para otimizar o efeito isqu&#234;mico e avaliar altera&#231;&#245;es na contratilidade segmentar, &#233; preciso usar doses maiores do que as necess&#225;rias para avalia&#231;&#227;o da perfus&#227;o e, por isso, os protocolos empregados no laborat&#243;rio de ecocardiografia de estresse devem adotar doses maiores e mais r&#225;pidas de vasodilatador em rela&#231;&#227;o &#224; cintilografia de perfus&#227;o. O resultado &#233; a elabora&#231;&#227;o de protocolos distintos.</p>
      <p>Os efeitos cardiovasculares da adenosina ex&#243;gena administrada por via intravenosa em seres humanos s&#227;o inibi&#231;&#227;o vagal e aumento da FC em doses baixas. Em doses altas, pode ocorrer inibi&#231;&#227;o do n&#243; sinusal e da condu&#231;&#227;o atrioventricular, bradicardia, BAV, estimula&#231;&#227;o simp&#225;tica, vasodilata&#231;&#227;o em todos os leitos arteriolares, exceto arter&#237;olas renais pr&#233;-glomerulares, onde promove vasoconstri&#231;&#227;o e hiperventila&#231;&#227;o, que &#233; explicada pela intera&#231;&#227;o com quimiorreceptores carot&#237;deos.</p>
      <sec>
        <title>7.1. Uso Durante a Ecocardiografia de Estresse</title>
        <p>A infus&#227;o intravenosa de adenosina promove o aumento discreto da FC e do d&#233;bito card&#237;aco e a diminui&#231;&#227;o discreta da press&#227;o sist&#234;mica (similar ao dipiridamol). A taquicardia leve ocorre apesar dos efeitos cronotr&#243;picos e dromotr&#243;picos negativos diretos da adenosina devido &#224; estimula&#231;&#227;o dos receptores mioc&#225;rdicos A1, por estimula&#231;&#227;o direta dos quimiorreceptores arteriais simp&#225;ticos excitat&#243;rios,<sup><xref ref-type="bibr" rid="B67">67</xref></sup> ou indiretamente, por vasodilata&#231;&#227;o sist&#234;mica (<xref ref-type="fig" rid="f12">Figura 7.1</xref>).</p>
        <fig id="f12">
          <label>Figura 7.1</label>
          <caption>
            <title>O uso de adenosina durante a ecocardiografia de estresse demonstra a contribui&#231;&#227;o importante do efeito vasodilatador no aumento da reserva de fluxo coronariano (RFC), com aumento progressivo e importante durante o exame, visto ap&#243;s 1,23 min de infus&#227;o da adenosina. A RFC passou de 16 cm/s no repouso para 42 cm/s.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>Em indiv&#237;duos normais, o fluxo sangu&#237;neo coronariano aumenta de quatro a cinco vezes o fluxo basal ap&#243;s a infus&#227;o de adenosina, um aumento compar&#225;vel &#224;quele causado por altas doses de dipiridamol e substancialmente maior do que aquele induzido por exerc&#237;cio ou dobutamina, durante o qual o fluxo sangu&#237;neo coronariano aumenta cerca de tr&#234;s vezes em rela&#231;&#227;o ao valor basal.<sup><xref ref-type="bibr" rid="B67">67</xref></sup> O efeito dilatador coronariano m&#225;ximo &#233; atingido at&#233; 2 minutos ap&#243;s a administra&#231;&#227;o de adenosina e desaparece rapidamente at&#233; 2&#8211;5 minutos ap&#243;s a interrup&#231;&#227;o da infus&#227;o.<sup><xref ref-type="bibr" rid="B68">68</xref></sup></p>
        <p>Teoricamente, o regadenoson tem caracter&#237;sticas atraentes, pr&#243;ximas &#224;s do agente "ideal", por seu r&#225;pido in&#237;cio de a&#231;&#227;o, dura&#231;&#227;o adequada do efeito, que permite a aquisi&#231;&#227;o da imagem, e menos efeitos colaterais. A raz&#227;o &#233; a estimula&#231;&#227;o seletiva dos receptores A2A especificamente respons&#225;veis pela vasodilata&#231;&#227;o coronariana, evitando os efeitos indesej&#225;veis da estimula&#231;&#227;o dos receptores A1, A2B e A3 (como dispneia, cefaleia e rubor). A incid&#234;ncia desses efeitos colaterais n&#227;o &#233; substancialmente reduzida em compara&#231;&#227;o com a adenosina, embora sua gravidade seja menor.<sup><xref ref-type="bibr" rid="B69">69</xref></sup></p>
        <sec>
          <title>7.1.1. Indica&#231;&#245;es</title>
          <p>A principal indica&#231;&#227;o do teste de estresse com adenosina ou regadenoson &#233; a detec&#231;&#227;o de DAC epic&#225;rdica ou microvascular que cause isquemia mioc&#225;rdica. Tamb&#233;m pode ser utilizado para avalia&#231;&#227;o de viabilidade mioc&#225;rdica, assim como o dipiridamol, por&#233;m com menor reprodutibilidade em compara&#231;&#227;o com a dobutamina.</p>
          <p>O hist&#243;rico de seguran&#231;a e a meia-vida curta tornam a adenosina especialmente indicada em pacientes com estenose a&#243;rtica grave,<sup><xref ref-type="bibr" rid="B70">70</xref>,<xref ref-type="bibr" rid="B71">71</xref></sup> no p&#243;s-operat&#243;rio de crian&#231;as assintom&#225;ticas submetidas &#224; opera&#231;&#227;o de troca arterial para transposi&#231;&#227;o das grandes art&#233;rias<sup><xref ref-type="bibr" rid="B72">72</xref></sup> e pacientes idosos,<sup><xref ref-type="bibr" rid="B73">73</xref></sup> que podem ser especialmente vulner&#225;veis a complica&#231;&#245;es durante o estresse com dipiridamol ou dobutamina.</p>
          <p>Pacientes com doen&#231;a pulmonar obstrutiva cr&#244;nica moderada ou grave que t&#234;m indica&#231;&#227;o para teste de estresse com imagem e querem evitar broncoconstri&#231;&#227;o e comprometimento respirat&#243;rio induzido por adenosina podem participar de aplica&#231;&#245;es emergentes de regadenoson,<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B74">74</xref>,<xref ref-type="bibr" rid="B75">75</xref></sup> embora nesses pacientes o uso de dobutamina possa ser mais razo&#225;vel.</p>
        </sec>
      </sec>
      <sec>
        <title>7.2. Protocolo para Ecocardiografia de Estresse com Adenosina</title>
        <p>A dose de 140 &#956;g/kg/min durante 6 minutos &#233; recomendada rotineiramente para isquemia mioc&#225;rdica. O aumento da dose at&#233; 160 e 210 &#956;g/kg/min pode ser aconselhado em caso de teste negativo na etapa de 140 &#956;g/kg/min e &#233; necess&#225;rio apenas em 16&#8211;18% dos casos.<sup><xref ref-type="bibr" rid="B68">68</xref>,<xref ref-type="bibr" rid="B76">76</xref>,<xref ref-type="bibr" rid="B77">77</xref></sup> Quando os efeitos colaterais s&#227;o intoler&#225;veis, a titula&#231;&#227;o decrescente da dose tamb&#233;m &#233; poss&#237;vel. Pode ser potencializada com atropina ou <italic>handgrip</italic>. A rotina de todo exame sob estresse deve incluir a monitoriza&#231;&#227;o da eletrocardiografia, da PA e, nesse caso, da oximetria de pulso.</p>
        <p>Aquisi&#231;&#245;es das imagens padronizadas visando todos os territ&#243;rios coronarianos (cortes apicais quatro c&#226;maras, duas c&#226;maras e tr&#234;s c&#226;maras ou paraesternal longitudinal, transverso do VE, apical quatro e duas c&#226;maras) devem ser realizadas em repouso, em est&#225;gio intermedi&#225;rio, com 2 minutos de infus&#227;o, antes do final da infus&#227;o e na fase de recupera&#231;&#227;o.</p>
        <p>Para a avalia&#231;&#227;o do fluxo de reserva na coron&#225;ria descendente anterior faz-se o registro da velocidade diast&#243;lica m&#225;xima do fluxo m&#233;dio-distal em repouso e durante a hiperemia m&#225;xima, que normalmente acontece dentro de 90 a 120 segundos da infus&#227;o, e antes do final da infus&#227;o.</p>
        <p>A dose de 100 &#956;g/kg/min durante 2 minutos pode ser utilizada para avalia&#231;&#227;o de viabilidade mioc&#225;rdica.</p>
      </sec>
      <sec>
        <title>7.3. Protocolo para Ecocardiografia de Estresse com Regadenoson</title>
        <p>Atualmente, o regadenoson &#233; administrado em bolus de 0,4 mg em uma solu&#231;&#227;o de 5 mL (sem ajuste de dose com base no peso) injetada ao longo de 10 segundos, seguida por um flush de soro fisiol&#243;gico de 5 mL para garantir a administra&#231;&#227;o adequada do medicamento. O tempo ideal para a aquisi&#231;&#227;o de imagens de perfus&#227;o &#233; de 2 a 10 minutos ap&#243;s a infus&#227;o do f&#225;rmaco. O regadenoson permite a avalia&#231;&#227;o combinada de imagens de perfus&#227;o mioc&#225;rdica e a an&#225;lise da motilidade segmentar e &#233; usado com mais frequ&#234;ncia nos Estados Unidos e no Reino Unido. A adi&#231;&#227;o de atropina pode ser utilizada para potencializar o estresse.<sup><xref ref-type="bibr" rid="B78">78</xref></sup></p>
      </sec>
      <sec>
        <title>7.4. Contraindica&#231;&#245;es</title>
        <p>As contraindica&#231;&#245;es absolutas s&#227;o hipotens&#227;o arterial e obstru&#231;&#227;o grave das vias a&#233;reas, broncoespasmo ativo e BAV de segundo ou terceiro grau a n&#227;o ser que protegidos por marca-passo. Deve-se evitar o uso desses agentes em pacientes com sinais ou sintomas de angina inst&#225;vel ou instabilidade cardiovascular.<sup><xref ref-type="bibr" rid="B75">75</xref></sup></p>
        <p>Drogas antianginosas e produtos que cont&#234;m xantinas diminuem a sensibilidade do teste de estresse com adenosina e, portanto, devem ser removidas 24 horas antes do estresse, incluindo alimentos como caf&#233;, ch&#225;s, chimarr&#227;o, chocolate, refrigerantes e at&#233; banana.</p>
      </sec>
      <sec>
        <title>7.5. Efeitos Colaterais</title>
        <p>Os efeitos colaterais s&#227;o comuns e podem se tornar um fator limitante em n&#250;mero significativo de pacientes &#8211; at&#233; 20%.<sup><xref ref-type="bibr" rid="B79">79</xref></sup> Os efeitos colaterais limitantes mais frequentes para os estressores vasodilatadores mediados por adenosina incluem falta de ar, rubor, cefaleia, hipotens&#227;o arterial, dor tor&#225;cica intoler&#225;vel (nem sempre relacionada &#224; isquemia subjacente, possivelmente induzida pela estimula&#231;&#227;o direta dos receptores de adenosina A1 mioc&#225;rdica) e BAV de alto grau. O BAV de grau I-II ocorre em 2% dos exames, a hipotens&#227;o arterial abaixo de 90 mmHg em 3% e o broncoespasmo grave em 0,1%.<sup><xref ref-type="bibr" rid="B80">80</xref>,<xref ref-type="bibr" rid="B81">81</xref></sup> Efeitos colaterais menores, como sensa&#231;&#227;o de calor, rubor, dor de cabe&#231;a, n&#225;useas e outros sintomas aparecem em 80-84% dos casos.<sup><xref ref-type="bibr" rid="B81">81</xref></sup> A redu&#231;&#227;o hemodinamicamente significativa da PAS (&gt; 20 mmHg) &#233; mais prov&#225;vel em pacientes com estenose a&#243;rtica grave.<sup><xref ref-type="bibr" rid="B82">82</xref></sup> A adenosina ex&#243;gena tem efeito cronotr&#243;pico e dromotr&#243;pico negativo ainda mais pronunciado que a adenosina end&#243;gena,<sup><xref ref-type="bibr" rid="B83">83</xref></sup> tornando a ocorr&#234;ncia de bloqueios atrioventriculares avan&#231;ados mais frequente com a adenosina do que com o dipiridamol e o trifosfato de adenosina em doses equivalentes. A maioria das rea&#231;&#245;es com adenosina se resolve em at&#233; 1 a 5 minutos. Em ocasi&#245;es muito raras, &#233; necess&#225;ria uma infus&#227;o de aminofilina.</p>
      </sec>
      <sec>
        <title>7.6. Acur&#225;cia Diagn&#243;stica</title>
        <p>Com base em meta-an&#225;lise publicada de 11 estudos, a ecocardiografia de estresse com adenosina, baseada em anormalidades da motilidade segmentar, apresentou a mesma sensibilidade (79%), especificidade (91,5%) e acur&#225;cia que a ecocardiografia de estresse f&#237;sico, a ecocardiografia com dipiridamol e a ecocardiografia com dobutamina, com especificidade superior em compara&#231;&#227;o &#224; imagem de estresse do SPECT.<sup><xref ref-type="bibr" rid="B84">84</xref></sup></p>
      </sec>
    </sec>
    <sec>
      <title>8. Outras Modalidades de Ecocardiografia de Estresse: Marca-Passo, Ergonovina, <italic>Handgrip</italic> e Hiperventila&#231;&#227;o</title>
      <sec>
        <title>8.1. Ecocardiografia de estresse por Marca-Passo</title>
        <p>Em pacientes com contraindica&#231;&#227;o para estresse f&#237;sico ou farmacol&#243;gico, o estresse por estimula&#231;&#227;o atrial transesof&#225;gica pode ser uma alternativa vi&#225;vel. A estimula&#231;&#227;o &#233; realizada por um marca-passo externo conectado a um eletrodo esof&#225;gico bipolar e a um cateter de registro protegidos por bainha de 10F, introduzido por via nasal ou oral sob anestesia t&#243;pica. Utiliza-se a menor corrente capaz de fornecer captura est&#225;vel, iniciando em 10 bpm acima da FC de repouso, com aumento de 20 bpm a cada 2 minutos, at&#233; 85% da FC m&#225;xima predita para a idade.<sup><xref ref-type="bibr" rid="B85">85</xref></sup> Os crit&#233;rios de interrup&#231;&#227;o s&#227;o sintomas intoler&#225;veis, arritmia significativa, ECG com infradesn&#237;vel do ST &#8805; 2 mm ap&#243;s 80 ms do ponto J, PAS &gt; 220 mmHg, PAD &gt; 110 mmHg e PAS &lt; 90 mmHg. Eventos adversos graves s&#227;o raros. Pode ocorrer BAV de segundo grau tipo Wenckebach. Em compara&#231;&#227;o com o estresse por dobutamina, apresenta menos hipotens&#227;o ou hipertens&#227;o arterial, arritmias ou sintomas limitantes, e tem tempo de dura&#231;&#227;o e recupera&#231;&#227;o mais curtos e FC alvo atingida mais frequentemente. H&#225; excelente concord&#226;ncia entre os dois m&#233;todos para a avalia&#231;&#227;o da motilidade segmentar parietal.<sup><xref ref-type="bibr" rid="B85">85</xref></sup> Em pacientes portadores de MCPD, o estresse pode ser provocado por programa&#231;&#227;o n&#227;o invasiva.<sup><xref ref-type="bibr" rid="B86">86</xref></sup> O alvo &#233; 85% da FC m&#225;xima ou sinais de isquemia. Apresenta sensibilidade de 70%, especificidade de 90% e acur&#225;cia de 78% para o diagn&#243;stico de DAC obstrutiva, sendo preditor independente de morte por qualquer causa.</p>
      </sec>
      <sec>
        <title>8.2. Associa&#231;&#227;o do <italic>Handgrip</italic> &#224; Ecocardiografia de Estresse</title>
        <p>O exerc&#237;cio isom&#233;trico por preens&#227;o das m&#227;os (<italic>handgrip</italic>) produz aumento discreto da FC e do consumo de oxig&#234;nio em compara&#231;&#227;o com o exerc&#237;cio isot&#244;nico. Entretanto, produz aumento s&#250;bito e mais significativo da PA. Com o uso de um dinam&#244;metro de m&#227;o, &#233; poss&#237;vel estabelecer um protocolo subm&#225;ximo (25-50% da preens&#227;o m&#225;xima) por 3-4 minutos.<sup><xref ref-type="bibr" rid="B87">87</xref></sup> Possui baixa sensibilidade isoladamente para a pesquisa de DAC obstrutiva, mas &#233; &#250;til quando associado a outras formas de estresse farmacol&#243;gico.<sup><xref ref-type="bibr" rid="B88">88</xref></sup> Quando associado ao <italic>strain</italic>, apresenta sensibilidade de 80%, especificidade de 66% e AUC de 0,77 para diagn&#243;stico de isquemia mioc&#225;rdica.<sup><xref ref-type="bibr" rid="B89">89</xref></sup> Tamb&#233;m &#233; utilizado como teste de estresse diast&#243;lico alternativo ao cicloerg&#244;metro para o diagn&#243;stico de ICFEp. Possui vantagem em rela&#231;&#227;o ao cicloerg&#244;metro quanto aos artefatos de movimento. O teste com 40% da contra&#231;&#227;o m&#225;xima por 3-5 minutos produz consumo de O<sub>2</sub> similar &#224; baixa carga com cicloerg&#244;metro (20 W), com aumento compar&#225;vel da rela&#231;&#227;o E/e&#180;.<sup><xref ref-type="bibr" rid="B90">90</xref></sup></p>
      </sec>
      <sec>
        <title>8.3. Ecocardiografia de Estresse com Ergonovina e Hiperventila&#231;&#227;o</title>
        <p>A ergonovina &#233; utilizada como teste de estresse por vasoconstri&#231;&#227;o. O protocolo inclui bolus endovenoso (0,025 a 0,05 mg) a cada 5 minutos at&#233; a ocorr&#234;ncia de sinais de isquemia ou dose total de 0,35 mg. Sua aplica&#231;&#227;o principal &#233; o diagn&#243;stico de angina vasoesp&#225;stica, com sensibilidade de cerca de 91% e especificidade de cerca de 88%. Em um estudo com 3.094 pacientes, o estresse por ergonovina foi positivo em 8,6%. N&#227;o houve infarto do mioc&#225;rdio ou morte documentada. Entretanto, 0,6% dos pacientes tiveram sintomas transit&#243;rios e um paciente apresentou morte s&#250;bita ressuscitada. O exame demonstrou valor progn&#243;stico para eventos card&#237;acos adversos maiores.<sup><xref ref-type="bibr" rid="B91">91</xref></sup> Outra forma de estresse utilizada para o diagn&#243;stico de angina vasoesp&#225;stica &#233; a hiperventila&#231;&#227;o associada ou n&#227;o ao estresse por imers&#227;o em &#225;gua fria. Consiste em um per&#237;odo de hiperventila&#231;&#227;o com respira&#231;&#227;o profunda a 30 ipm por 6 minutos, seguido de imers&#227;o da m&#227;o em &#225;gua gelada por 2 minutos. Utiliza-se monitoriza&#231;&#227;o com ECG e ecocardiografia durante o estresse e ap&#243;s 15 minutos do t&#233;rmino. O crit&#233;rio de suspens&#227;o &#233; a presen&#231;a de dor tor&#225;cica e eleva&#231;&#227;o do ST &gt; 1 mm em ao menos duas deriva&#231;&#245;es. O surgimento de altera&#231;&#227;o segmentar nova durante o estresse &#233; crit&#233;rio para diagn&#243;stico de vasoespasmo. Em compara&#231;&#227;o com a inje&#231;&#227;o de acetilcolina intracoron&#225;ria durante angiografia, o m&#233;todo apresenta sensibilidade de cerca de 91%, especificidade de 90% e acur&#225;cia de 91%.<sup><xref ref-type="bibr" rid="B92">92</xref>,<xref ref-type="bibr" rid="B93">93</xref></sup></p>
      </sec>
    </sec>
    <sec>
      <title>9. Ecocardiografia de Estresse Diast&#243;lico</title>
      <p>A ICFEp &#233; um importante problema de sa&#250;de p&#250;blica em todo o mundo e se agrava &#224; medida que a popula&#231;&#227;o envelhece e adquire mais comorbidades. A manifesta&#231;&#227;o cl&#237;nica mais comum &#233; a dispneia ao esfor&#231;o.<sup><xref ref-type="bibr" rid="B94">94</xref>,<xref ref-type="bibr" rid="B95">95</xref></sup> O diagn&#243;stico &#233; complexo nos pacientes que apresentam sintomas apenas no exerc&#237;cio, pois os pept&#237;deos natriur&#233;ticos, o d&#233;bito card&#237;aco (DC) e a press&#227;o de enchimento do VE (PEVE) podem estar normais ou levemente alterados em rela&#231;&#227;o aos indiv&#237;duos com fun&#231;&#227;o diast&#243;lica (FD) normal. Nesses casos, o aumento da PEVE fica evidente apenas no exerc&#237;cio, ressaltando a import&#226;ncia de teste de esfor&#231;o.<sup><xref ref-type="bibr" rid="B94">94</xref>,<xref ref-type="bibr" rid="B95">95</xref></sup> A ecocardiografia de estresse diast&#243;lico (EEDiast) &#233; uma op&#231;&#227;o capaz de fornecer informa&#231;&#245;es nesses casos dif&#237;ceis, utilizando par&#226;metros da avalia&#231;&#227;o da FD do VE em repouso e durante exerc&#237;cio.<sup><xref ref-type="bibr" rid="B96">96</xref>-<xref ref-type="bibr" rid="B98">98</xref></sup></p>
      <sec>
        <title>9.1. Resposta Normal e Anormal ao Exerc&#237;cio na Fun&#231;&#227;o Diast&#243;lica</title>
        <p>A FD normal permite o enchimento adequado do VE em repouso e durante exerc&#237;cio, com aumento do DC, sem eleva&#231;&#227;o da PEVE. Os par&#226;metros mais estudados s&#227;o a rela&#231;&#227;o da velocidade m&#225;xima do enchimento inicial mitral (E) pela velocidade diast&#243;lica precoce (e&#8217;) no Doppler tecidual do anel mitral em repouso e durante exerc&#237;cio. No relaxamento normal, durante o exerc&#237;cio, ocorre aumento proporcional dessas velocidades, mantendo a rela&#231;&#227;o E/e&#8217; inalterada.<sup><xref ref-type="bibr" rid="B96">96</xref>,<xref ref-type="bibr" rid="B97">97</xref></sup> Nos pacientes com doen&#231;a mioc&#225;rdica e relaxamento anormal, n&#227;o h&#225; o aumento de e&#8217; equivalente ao de E, sendo esperado aumento da rela&#231;&#227;o E/e&#8217;. Valores de E/e&#8217; durante o exerc&#237;cio &lt; 10 sugerem PEVE normal, enquanto um valor de &gt; 14 (e&#8217; m&#233;dia) ou &gt;15 (usando somente a e&#8217; septal) sugere aumento da PEVE. A estimativa da press&#227;o sist&#243;lica da art&#233;ria pulmonar (PSAP) pela velocidade m&#225;xima do refluxo tric&#250;spide (VMRT) em repouso e durante exerc&#237;cio tamb&#233;m &#233; &#250;til, j&#225; que a PSAP se eleva com o aumento da PEVE.<sup><xref ref-type="bibr" rid="B94">94</xref>,<xref ref-type="bibr" rid="B97">97</xref></sup></p>
      </sec>
      <sec>
        <title>9.2. Indica&#231;&#245;es para Ecocardiografia de Estresse</title>
        <p>Para os pacientes com ICFEp com dispneia ao exerc&#237;cio, a avalia&#231;&#227;o em repouso pode ser insuficiente, justificando a avalia&#231;&#227;o com exerc&#237;cio para determinar aumento da PEVE.<sup><xref ref-type="bibr" rid="B94">94</xref>,<xref ref-type="bibr" rid="B97">97</xref></sup> Diretrizes de diferentes sociedades sugerem a EEDiast na suspeita cl&#237;nica de ICFEp.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B94">94</xref>,<xref ref-type="bibr" rid="B98">98</xref>,<xref ref-type="bibr" rid="B99">99</xref></sup> A <xref ref-type="fig" rid="f13">Figura 9.1</xref> exemplifica as recomenda&#231;&#245;es.</p>
        <fig id="f13">
          <label>Figura 9.1</label>
          <caption>
            <title>Indica&#231;&#245;es de ecocardiografia de estresse diast&#243;lico segundo as diretrizes.<sup><xref ref-type="bibr" rid="B94">94</xref>,<xref ref-type="bibr" rid="B95">95</xref>,<xref ref-type="bibr" rid="B98">98</xref>,<xref ref-type="bibr" rid="B100">100</xref></sup></title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>O escore HFA-PEFF &#233; o sugerido pela Sociedade Europeia para diagn&#243;stico de ICFEP, enquanto o escore H<sub>2</sub>FPEF &#233; o citado na diretriz americana para diagn&#243;stico de ICFEp.</p>
      </sec>
      <sec>
        <title>9.3. Protocolos Utilizados na Ecocardiografia de Estresse Diast&#243;lico</title>
        <p>A EEDiast pode ser realizada com bicicleta ou esteira ergom&#233;trica ou na ciclomaca. A bicicleta na posi&#231;&#227;o supina (ciclomaca) &#233; a mais sugerida pelas avalia&#231;&#245;es da contratilidade segmentar e da FD durante os est&#225;gios e no pico.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B94">94</xref>,<xref ref-type="bibr" rid="B99">99</xref></sup> A esteira pode ser utilizada e a avalia&#231;&#227;o da contratilidade segmentar realizada ap&#243;s cessar o exerc&#237;cio (60-90 segundos ap&#243;s), sendo a FD avaliada a seguir. Em ambas as modalidades, os pacientes s&#227;o estimulados a atingirem a FC m&#225;xima prevista para a idade ou o surgimento de sintomas limitantes. As <xref ref-type="table" rid="t12">Tabelas 9.1</xref> e <xref ref-type="table" rid="t13">9.2</xref> mostram as vantagens e limita&#231;&#245;es dos protocolos e vari&#225;veis obtidas<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B98">98</xref></sup> e os par&#226;metros adquiridos na ecocardiografia de estresse diast&#243;lico.</p>
        <table-wrap id="t12">
          <label>Tabela 9.1</label>
          <caption>
            <title>Protocolos, vantagens e limita&#231;&#245;es</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 style="background-color:#76B4CF">
                <th align="left" valign="middle">Modalidade</th>
                <th align="center" valign="middle">Protocolos</th>
                <th align="center" valign="middle">Vantagens</th>
                <th align="center" valign="middle">Limita&#231;&#245;es</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle">Bicicleta</td>
                <td align="center" valign="middle">Padr&#227;o: carga inicial 25 W, 60 rpm, incrementos de 25 W cada 2 ou 3 minutos.</td>
                <td align="center" valign="middle">- Fisiol&#243;gico.<break/> - Mais tempo para aquisi&#231;&#227;o.<break/> - Mais estudos com valida&#231;&#227;o.</td>
                <td align="center" valign="middle">- Pouca disponibilidade.<break/> - Dificuldade para obten&#231;&#227;o das imagens.<break/> - Menor carga de trabalho alcan&#231;ado em rela&#231;&#227;o &#224; esteira.</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">Esteira</td>
                <td align="center" valign="middle">Bruce: inclina&#231;&#227;o inicial de 10% e incrementos de 2% a cada est&#225;gio de 3 minutos.<break/> Bruce modificado: inclina&#231;&#227;o inicial de 0%, dura&#231;&#227;o de 3 minutos a cada est&#225;gio e incrementos na inclina&#231;&#227;o.</td>
                <td align="center" valign="middle">- Fisiol&#243;gico.<break/> - Disponibilidade.<break/> - Alcan&#231;a altas cargas de trabalho.<break/> - Maior duplo produto &#224; custa de FC mais elevada.<break/> - Mais espec&#237;fico para detectar isquemia do que a bicicleta.</td>
                <td align="center" valign="middle">- Dificuldade em adquirir imagens.<break/> - Possibilidade de normaliza&#231;&#227;o das altera&#231;&#245;es no p&#243;s-exerc&#237;cio.<break/> - Aguardar FC na recupera&#231;&#227;o &lt; 100-110/min (evitar a fus&#227;o das ondas do Doppler).<break/> - Sem valida&#231;&#227;o hemodin&#226;mica.</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN6">
              <p>W: Watts; rpm: rota&#231;&#245;es por minuto; FC: frequ&#234;ncia card&#237;aca.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <table-wrap id="t13">
          <label>Tabela 9.2</label>
          <caption>
            <title>Par&#226;metros adquiridos na ecocardiografia de estresse diast&#243;lico no repouso e durante (bicicleta) ou p&#243;s-exerc&#237;cio imediato (esteira)</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 style="background-color:#76B4CF">
                <th align="left" valign="middle">Par&#226;metro</th>
                <th align="center" valign="middle">Aquisi&#231;&#227;o</th>
                <th align="center" valign="middle">Vantagens</th>
                <th align="center" valign="middle">Limita&#231;&#245;es</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle">E</td>
                <td align="center" valign="middle">- Apical 4 c&#226;maras.<break/> - Medir no pico da velocidade inicial diast&#243;lica.</td>
                <td align="center" valign="middle">Fact&#237;vel e reprodut&#237;vel.</td>
                <td align="center" valign="middle">- Fus&#227;o das velocidades E e A com FC elevada.<break/> - Diminui com a idade.<break/> - Adquirir quando a FC est&#225; entre 100 e 110 bpm.</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">e&#8217; (lateral, medial)</td>
                <td align="center" valign="middle">- Apical 4 c&#226;maras.<break/> - Doppler tecidual do anel mitral<break/> na regi&#227;o septal e lateral.</td>
                <td align="center" valign="middle">Fact&#237;vel e reprodut&#237;vel.</td>
                <td align="center" valign="middle">- Fus&#227;o das velocidades e&#8217; e a&#8217; com FC elevada.<break/> - Diminui com a idade.<break/> - Acur&#225;cia limitada em pacientes com calcifica&#231;&#227;o do anel mitral, anel prot&#233;tico, doen&#231;a peric&#225;rdica.</td>
              </tr>
              <tr>
                <td align="left" valign="middle">Rela&#231;&#227;o E/e&#8217;</td>
                <td align="center" valign="middle">- Raz&#227;o entre as velocidades E, e&#8217;.</td>
                <td align="center" valign="middle">Valida&#231;&#227;o hemodin&#226;mica.</td>
                <td align="center" valign="middle">- Acur&#225;cia diminu&#237;da em indiv&#237;duos normais, calcifica&#231;&#227;o do anel mitral, doen&#231;a mitral e peric&#225;rdica significativas, altera&#231;&#227;o da contra&#231;&#227;o segmentar.</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">VMRT</td>
                <td align="center" valign="middle">- Apical 4 c&#226;maras ou paraesternal via de entrada do VD.<break/> - Doppler cont&#237;nuo.</td>
                <td align="center" valign="middle">Adjunto indireto da estimativa da press&#227;o de enchimento do VE.</td>
                <td align="center" valign="middle">- Pode acontecer aumento da velocidade por doen&#231;a ou resposta normal ao aumento de fluxo no exerc&#237;cio.<break/> - Sinal completo n&#227;o &#233; obtido em 1/3 dos pacientes.<break/> - Menos confi&#225;vel se houver regurgita&#231;&#227;o tric&#250;spide acentuada.</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN7">
              <p>VE: ventr&#237;culo esquerdo; VD: ventr&#237;culo direito; E: velocidade m&#225;xima do enchimento inicial mitral; A: velocidade tardia do enchimento do VE pela s&#237;stole atrial; e&#8217;: velocidade diast&#243;lica precoce no Doppler tecidual do anel mitral; FC: frequ&#234;ncia card&#237;aca; bpm: batimentos por minuto; VMRT: velocidade m&#225;xima do refluxo tric&#250;spide.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>9.4. Interpreta&#231;&#227;o da Ecocardiografia de Estresse Diast&#243;lico</title>
        <p>A capacidade funcional deve ser comparada com o esperado para a idade e o sexo do paciente.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B94">94</xref>,<xref ref-type="bibr" rid="B99">99</xref></sup> A <xref ref-type="table" rid="t14">Tabela 9.3</xref> mostra as respostas normal e alterada de pacientes submetidos a EEDiast.</p>
        <table-wrap id="t14">
          <label>Tabela 9.3</label>
          <caption>
            <title>Achados ecocardiogr&#225;ficos poss&#237;veis encontrados na ecocardiografia de estresse diast&#243;lico</title>
          </caption>
          <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 style="background-color:#76B4CF">
                <th align="left" valign="middle"/>
                <th align="center" valign="middle" colspan="2">Ecocardiografia de estresse diast&#243;lico com fun&#231;&#227;o diast&#243;lica normal</th>
                <th align="center" valign="middle" colspan="2">Ecocardiografia de estresse diast&#243;lico com disfun&#231;&#227;o diast&#243;lica</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle"/>
                <td align="center" valign="middle">Pr&#233;-exerc&#237;cio</td>
                <td align="center" valign="middle">Durante ou imediatamente ap&#243;s exerc&#237;cio</td>
                <td align="center" valign="middle">Pr&#233;-exerc&#237;cio<xref ref-type="table-fn" rid="TFN9">**</xref></td>
                <td align="center" valign="middle">Durante ou imediatamente ap&#243;s exerc&#237;cio</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">E/e&#8217; septal (m&#233;dia)</td>
                <td align="center" valign="middle">&lt; 10</td>
                <td align="center" valign="middle">&lt; 10</td>
                <td align="center" valign="middle">&lt; 14</td>
                <td align="center" valign="middle">&gt; 15 (&gt;14)</td>
              </tr>
              <tr>
                <td align="left" valign="middle">VMRT<xref ref-type="table-fn" rid="TFN8">*</xref> (m/s)</td>
                <td align="center" valign="middle">&lt; 2,8</td>
                <td align="center" valign="middle">&lt; 2,8</td>
                <td align="center" valign="middle">&lt; 2,8</td>
                <td align="center" valign="middle">&gt; 2,8 / &gt;3,4</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN8">
              <label>*</label>
              <p>Os valores de VMRT s&#227;o diferentes de acordo com as diretrizes. Segundo a ASE/EACVI, &#233; considerado alterado quando VMRT &gt; 2,8 m/s (maior sensibilidade); de acordo com a HFA/ESC, &#233; alterado quando VMRT &gt; 3,4 m/s (maior especificidade).<sup><xref ref-type="bibr" rid="B94">94</xref>,<xref ref-type="bibr" rid="B99">99</xref></sup></p>
            </fn>
            <fn id="TFN9">
              <label>**</label>
              <p>Na EEDiast alterada, as velocidades de e&#8217; septal em repouso devem ser &lt; 7 cm/s, ou, se somente a e&#8217; lateral for avaliada, devem ser &lt; 10 cm/s.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>A EEDiast &#233; importante para detectar altera&#231;&#245;es que n&#227;o se apresentam em repouso e que se apresentam apenas sob exerc&#237;cio f&#237;sico, e as diretrizes atuais recomendam seu uso para identificar pacientes portadores de ICFEp.</p>
      </sec>
    </sec>
    <sec>
      <title>10. Ecocardiografia de Estresse no MINOCA (Aus&#234;ncia de Coronariopatia Obstrutiva) e na Doen&#231;a Microvascular</title>
      <p>Define-se MINOCA (do ingl&#234;s, <italic>myocardial infarction with non-obstructive coronary arteries</italic>) os casos de s&#237;ndrome coronariana aguda (SCA) com aumento da troponina acima do 99&#186; percentil e sintomas ou altera&#231;&#245;es eletrocardiogr&#225;ficas na aus&#234;ncia de doen&#231;a coron&#225;ria epic&#225;rdica com obstru&#231;&#245;es maiores que 50%.<sup><xref ref-type="bibr" rid="B101">101</xref></sup> O MINOCA corresponde a aproximadamente 5-10% das SCAs.<sup><xref ref-type="bibr" rid="B101">101</xref>,<xref ref-type="bibr" rid="B102">102</xref></sup> O progn&#243;stico dos pacientes com MINOCA &#233; vari&#225;vel e depende do mecanismo subjacente.<sup><xref ref-type="bibr" rid="B101">101</xref></sup> Essa condi&#231;&#227;o &#233; mais prevalente em indiv&#237;duos mais jovens, particularmente mulheres, e os fatores de risco convencionais para doen&#231;a coronariana, como dislipidemia, tabagismo e hist&#243;rico familiar, t&#234;m uma preval&#234;ncia reduzida.<sup><xref ref-type="bibr" rid="B103">103</xref>,<xref ref-type="bibr" rid="B104">104</xref></sup> A identifica&#231;&#227;o de MINOCA, excluindo os diagn&#243;sticos diferenciais poss&#237;veis, &#233; de extrema import&#226;ncia para o manejo cl&#237;nico apropriado e precoce.<sup><xref ref-type="bibr" rid="B104">104</xref></sup></p>
      <sec>
        <title>10.1. Fisiopatologia</title>
        <p>Atualmente, o MINOCA pode ser classificado em 2 tipos:<sup><xref ref-type="bibr" rid="B103">103</xref>,<xref ref-type="bibr" rid="B104">104</xref></sup></p>
        <list list-type="bullet">
          <list-item>
            <p>Tipo I: Eventos relacionados a placas: rotura, eros&#227;o e dissec&#231;&#227;o da parede da coron&#225;ria;</p>
          </list-item>
          <list-item>
            <p>Tipo II: Desequil&#237;brio entre oferta e consumo de O<sub>2</sub>, os quais ocorrerem nas seguintes situa&#231;&#245;es: espasmo coronariano, embolia coronariana, disfun&#231;&#227;o endotelial, anemia, hipertens&#227;o, hipotens&#227;o, extremos de FC e hipoxemia.</p>
          </list-item>
        </list>
        <p>&#201; importante ressaltar que situa&#231;&#245;es como a s&#237;ndrome de Takotsubo n&#227;o s&#227;o consideradas MINOCA, pois n&#227;o apresentam natureza isqu&#234;mica. No entanto, h&#225; relatos de doen&#231;a coronariana associada em 10-29% dos pacientes com s&#237;ndrome de Takotsubo.<sup><xref ref-type="bibr" rid="B104">104</xref></sup> Outros diagn&#243;sticos diferenciais devem ser considerados e investigados extensivamente: miocardites, altera&#231;&#245;es relacionadas a sepse, tromboembolismo pulmonar e contus&#227;o card&#237;aca. Entre as causas isqu&#234;micas, o estudo hemodin&#226;mico invasivo para detectar a presen&#231;a de obstru&#231;&#227;o coronariana significativa ou a oclus&#227;o de pequenos ramos secund&#225;rios se faz necess&#225;rio.<sup><xref ref-type="bibr" rid="B101">101</xref>-<xref ref-type="bibr" rid="B104">104</xref></sup></p>
      </sec>
      <sec sec-type="methods">
        <title>10.2. Principais M&#233;todos Diagn&#243;sticos no MINOCA</title>
        <p>O diagn&#243;stico inicia pelo quadro t&#237;pico de dor precordial e aumento da troponina acima do 99&#186; percentil, com comportamento de curva, associado ou n&#227;o a altera&#231;&#245;es eletrocardiogr&#225;ficas.<sup><xref ref-type="bibr" rid="B104">104</xref></sup> Diante do quadro de SCA, o paciente &#233; submetido a angiocoronariografia, e a obstru&#231;&#227;o &#8805; 50% &#233; exclu&#237;da pela revis&#227;o cuidadosa das imagens. O diagn&#243;stico anatomofuncional pode ser complementado com o uso de ultrassom intracoron&#225;rio e tomografia de coer&#234;ncia &#243;ptica, m&#233;todos que permitem analisar as caracter&#237;sticas da placa e identificar a presen&#231;a de rotura. A medida do fluxo fracionado de reserva mioc&#225;rdica pode identificar placas que visualmente t&#234;m obstru&#231;&#227;o menor que 50%, mas com repercuss&#227;o significativa.<sup><xref ref-type="bibr" rid="B103">103</xref>-<xref ref-type="bibr" rid="B105">105</xref></sup></p>
        <p>Atualmente, a RNM card&#237;aca desponta como o exame de escolha para avalia&#231;&#227;o de pacientes com suspeita de MINOCA. Esse m&#233;todo proporciona um diagn&#243;stico diferencial preciso de situa&#231;&#245;es cl&#237;nicas que mimetizam MINOCA. Liang et al.<sup><xref ref-type="bibr" rid="B102">102</xref></sup> reportam, em estudo retrospectivo com mais de 800 pacientes em que a RNM reclassifica os pacientes com MINOCA, que somente 27% dos casos considerados eram realmente MINOCA, enquanto 73% dos casos representavam outras patologias, como miocardites.</p>
        <p>A <xref ref-type="fig" rid="f14">Figura 10.1</xref> representa a sequ&#234;ncia de exames que pode ser seguida na suspeita de MINOCA.</p>
        <fig id="f14">
          <label>Figura 10.1</label>
          <caption>
            <title>Algoritmo para o diagn&#243;stico e/ou estratifica&#231;&#227;o de MINOCA. SCA: S&#237;ndrome coronariana aguda; ETT: ecocardiografia transtor&#225;cica; TEP: tromboembolismo pulmonar; S.: S&#237;ndrome; RNM: resson&#226;ncia magn&#233;tica; OCT: Tomografia de coer&#234;ncia &#243;tica; ETE: ecocardiografia transesof&#225;gica. Adaptado de Del Buono et al.<sup><xref ref-type="bibr" rid="B107">107</xref></sup></title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>A ecocardiografia de estresse farmacol&#243;gico tem seu papel no MINOCA ao avaliar aus&#234;ncia de altera&#231;&#245;es segmentares ou de forma mais assertiva nos casos de vasoespasmo, os quais podem ser diagnosticados na fase de recupera&#231;&#227;o dos testes farmacol&#243;gicos com infus&#227;o mais r&#225;pida de betabloqueadores ou aminofilina.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B106">106</xref></sup></p>
      </sec>
      <sec>
        <title>10.3. Ecocardiografia de Estresse no MINOCA</title>
        <p>Na &#250;ltima Diretriz Brasileira de Angina e Infarto da Sociedade Brasileira de Cardiologia,<sup><xref ref-type="bibr" rid="B103">103</xref></sup> observa-se indica&#231;&#227;o IIa para ecocardiografia de estresse no MINOCA de origem microvascular, com o objetivo de estratifica&#231;&#227;o de risco, pois a presen&#231;a de altera&#231;&#245;es de contra&#231;&#227;o segmentar implica pior progn&#243;stico.</p>
        <p>A cascata isqu&#234;mica no MINOCA apresenta um comportamento diferente daquela observada na doen&#231;a epic&#225;rdica, chamada de cascata isqu&#234;mica alternativa e cl&#225;ssica, respectivamente (<xref ref-type="fig" rid="f15">Figura 10.2</xref>). Na cascata alternativa, a altera&#231;&#227;o prim&#225;ria ocorre na redu&#231;&#227;o do fluxo de reserva coronariano. Dessa forma, o protocolo padr&#227;o de ecocardiografia de estresse somente com avalia&#231;&#227;o da contra&#231;&#227;o segmentar tem baixa sensibilidade. Logo, o protocolo ABCDE<sup><xref ref-type="bibr" rid="B106">106</xref></sup> &#233; indicado para aumentar a acur&#225;cia do exame e estratificar o risco. Nesse protocolo, avalia-se os volumes ventriculares e contra&#231;&#227;o segmentar (A), o ultrassom de pulm&#227;o para pesquisa de congest&#227;o nos quatro segmentos tor&#225;cicos anteriores (B), a reserva contr&#225;til do VE pelo c&#225;lculo da FE pelo m&#233;todo volum&#233;trico (C), a RFC na ADA por Doppler (D) e o ECG (E) para an&#225;lise da reserva cronotr&#243;pica.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> Sendo assim, recomendamos o uso do protocolo ABCDE, descrito em outra se&#231;&#227;o desta diretriz.<sup><xref ref-type="bibr" rid="B106">106</xref></sup> Muitos pacientes referem dor tor&#225;cica ao exame, a qual n&#227;o ocorre ao final da cascata isqu&#234;mica cl&#225;ssica, mas sim no in&#237;cio.</p>
        <fig id="f15">
          <label>Figura 10.2</label>
          <caption>
            <title>Compara&#231;&#227;o da cascata isqu&#234;mica na doen&#231;a epic&#225;rdica (cl&#225;ssica) e no MINOCA (alternativa). Adaptado de Picano et al.<sup><xref ref-type="bibr" rid="B2">2</xref></sup></title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>A utiliza&#231;&#227;o de agentes de realce ultrassonogr&#225;fico pode ser aplicada para avalia&#231;&#227;o da opacifica&#231;&#227;o do VE e an&#225;lise de bordos endoc&#225;rdicos, como utilizado na doen&#231;a coronariana epic&#225;rdica.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup> Seu uso para a an&#225;lise de reserva coronariana no protocolo ABCDE e pesquisa de perfus&#227;o mioc&#225;rdica (<italic>off label</italic>), em centros com conhecimento especializado, pode ser &#250;til.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup></p>
        <p>Vale ressaltar que o MINOCA &#233; um diagn&#243;stico de exclus&#227;o na SCA, no qual a ecocardiografia de estresse tem papel diagn&#243;stico principalmente na doen&#231;a microvascular e no espasmo coronariano, aliado ao protocolo ABCDE para aumentar a sensibilidade do exame.</p>
      </sec>
    </sec>
    <sec>
      <title>11. Ecocardiografia de Estresse na Doen&#231;a Valvar Mitral</title>
      <p>A ecocardiografia de estresse tem papel importante em auxiliar no refinamento do diagn&#243;stico de gravidade, na estratifica&#231;&#227;o progn&#243;stica e na defini&#231;&#227;o terap&#234;utica para pacientes com doen&#231;a valvar mitral (DVM), sendo realizada preferencialmente por estresse f&#237;sico.<sup><xref ref-type="bibr" rid="B108">108</xref>,<xref ref-type="bibr" rid="B109">109</xref></sup> Condi&#231;&#245;es fisiol&#243;gicas e doen&#231;as associadas podem modificar a apresenta&#231;&#227;o cl&#237;nica e interferir na acur&#225;cia dos m&#233;todos diagn&#243;sticos convencionais na avalia&#231;&#227;o da gravidade das patologias mitrais, que sofre influ&#234;ncia de condi&#231;&#245;es hemodin&#226;micas, como pr&#233;-carga, p&#243;s-carga e FC. Em alguns casos podemos ter crit&#233;rios de gravidade discordantes ao ecocardiograma, ou mesmo a dificuldade em avaliar os sintomas em determinados pacientes (aspectos socioculturais, altera&#231;&#245;es cognitivas, sedent&#225;rios), podendo ocorrer a chamada "dissocia&#231;&#227;o cl&#237;nico-ecocardiogr&#225;fica". &#201; importante considerar a complementa&#231;&#227;o com outros m&#233;todos de imagem e a avalia&#231;&#227;o funcional com a ecocardiografia de estresse para uma melhor defini&#231;&#227;o terap&#234;utica.</p>
      <p>H&#225; tr&#234;s indica&#231;&#245;es b&#225;sicas de ecocardiografia de estresse para avalia&#231;&#227;o de doen&#231;as valvares mitrais nativas: 1) DVM grave assintom&#225;tica, 2) DVM n&#227;o grave sintom&#225;tica, 3) DVM com baixo fluxo transvalvar. O uso do exerc&#237;cio f&#237;sico &#233; o mais indicado para o estudo da DVM, pois possibilita a avalia&#231;&#227;o de toler&#226;ncia f&#237;sica e dos sintomas e a obten&#231;&#227;o de dados hemodin&#226;micos de forma fisiol&#243;gica (reprodut&#237;veis com atividades da vida di&#225;ria), embora a dobutamina possa tamb&#233;m ser utilizada em casos de estenose mitral (EM) em pacientes com limita&#231;&#227;o ao exerc&#237;cio.<sup><xref ref-type="bibr" rid="B110">110</xref></sup> Para a ecocardiografia de estresse, pode ser utilizado a esteira ergom&#233;trica, a bicicleta ergom&#233;trica ou ciclomaca; a &#250;ltima tem a vantagem de permitir a an&#225;lise ecocardiogr&#225;fica cont&#237;nua, o que possibilita evidenciar altera&#231;&#245;es em baixa carga (antes do pico do esfor&#231;o) e obter dados e imagens do pico do exerc&#237;cio, que podem ser subestimados com o uso de esteira, pois a captura &#233; realizada ap&#243;s o pico de esfor&#231;o.</p>
      <sec>
        <title>11.1. Estenose Mitral</title>
        <p>A EM reum&#225;tica ainda &#233; um importante problema de sa&#250;de p&#250;blica no Brasil e em pa&#237;ses em desenvolvimento, com alta incid&#234;ncia na &#193;frica e algumas regi&#245;es da &#193;sia e Am&#233;rica Latina,<sup><xref ref-type="bibr" rid="B111">111</xref>,<xref ref-type="bibr" rid="B112">112</xref></sup> sendo a causa mais prevalente de EM no mundo, seguida pelas doen&#231;as degenerativas. A incid&#234;ncia de estenose degenerativa mitral relacionada a calcifica&#231;&#227;o anular mitral aumenta com a idade e &#233; a causa predominante nos pa&#237;ses industrializados.<sup><xref ref-type="bibr" rid="B113">113</xref></sup></p>
        <p>A ecocardiografia de estresse tem indica&#231;&#227;o validada para a avalia&#231;&#227;o de gravidade da EM e sua repercuss&#227;o hemodin&#226;mica, especialmente em pacientes que apresentam discrep&#226;ncia entre o grau de estenose determinada pelos m&#233;todos de imagem e cl&#237;nicos.<sup><xref ref-type="bibr" rid="B108">108</xref>,<xref ref-type="bibr" rid="B114">114</xref>,<xref ref-type="bibr" rid="B115">115</xref></sup> Pacientes com EMs quantificadas como moderadas &#224; ecocardiografia de repouso muitas vezes s&#227;o bastante sintom&#225;ticos ao esfor&#231;o, e a ecocardiografia de estresse pode, em alguns casos, demonstrar as altera&#231;&#245;es hemodin&#226;micas que justificam esses sintomas, com aumento significativo de gradientes transvalvares e PSAP (<xref ref-type="table" rid="t15">Tabela 11.1</xref>). S&#227;o estabelecidos como crit&#233;rios de mau progn&#243;stico o aumento do gradiente m&#233;dio em valor absoluto acima de 15 mmHg com o esfor&#231;o<sup><xref ref-type="bibr" rid="B108">108</xref>,<xref ref-type="bibr" rid="B110">110</xref></sup> ou o aumento da PSAP acima de 60 mmHg.<sup><xref ref-type="bibr" rid="B116">116</xref></sup> Outras situa&#231;&#245;es em que a ecocardiografia de estresse pode ser &#250;til na EM incluem pacientes que ser&#227;o submetidos a grandes cirurgias ou que pretendem engravidar, para predizer o comportamento da doen&#231;a em situa&#231;&#245;es hemodin&#226;micas adversas.<sup><xref ref-type="bibr" rid="B117">117</xref></sup> Em casos de pacientes com limita&#231;&#227;o ao exerc&#237;cio, pode ser utilizada ecocardiografia de estresse farmacol&#243;gico com dobutamina, que est&#225; validada para essa situa&#231;&#227;o, e nesse caso o valor absoluto do gradiente m&#233;dio que denota pior progn&#243;stico &#233; de 18mmHg.<sup><xref ref-type="bibr" rid="B118">118</xref></sup></p>
        <table-wrap id="t15">
          <label>Tabela 11.1</label>
          <caption>
            <title>Uso da ecocardiografia de estresse na avalia&#231;&#227;o das patologias valvares mitrais<sup><xref ref-type="bibr" rid="B116">116</xref>,<xref ref-type="bibr" rid="B108">108</xref>,<xref ref-type="bibr" rid="B110">110</xref>,<xref ref-type="bibr" rid="B117">117</xref></sup></title>
          </caption>
          <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 style="background-color:#76B4CF">
                <th align="left" valign="middle">Patologia mitral</th>
                <th align="center" valign="middle">Tipos de estresse</th>
                <th align="center" valign="middle">Crit&#233;rios estabelecidos em diretrizes</th>
                <th align="center" valign="middle">Crit&#233;rios estabelecidos em estudos cl&#237;nicos</th>
                <th align="center" valign="middle">Par&#226;metros que podem ser avaliados</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle">Insufici&#234;ncia mitral prim&#225;ria</td>
                <td align="left" valign="middle">Exerc&#237;cio f&#237;sico</td>
                <td align="left" valign="middle">-</td>
                <td align="left" valign="middle">Aumento de PSAP induzida pelo exerc&#237;cio &gt; 60 mmHg<break/> Reserva contr&#225;til<break/> Aumento de EROA induzida pelo exerc&#237;cio &gt; 10 mm</td>
                <td align="left" valign="middle">
                  <list list-type="bullet">
                    <list-item>
                      <p>Sintomas</p>
                    </list-item>
                    <list-item>
                      <p>Resposta press&#243;rica</p>
                    </list-item>
                    <list-item>
                      <p>PSAP induzida pelo exerc&#237;cio &gt; 60 mmHg</p>
                    </list-item>
                    <list-item>
                      <p>Novas altera&#231;&#245;es da contratilidade segmentar</p>
                    </list-item>
                    <list-item>
                      <p>Aumento da FEVE induzida pelo esfor&#231;o &lt; ou &gt; 5%</p>
                    </list-item>
                    <list-item>
                      <p>Aumento do GLS &lt; ou &gt; 2% induzido pelo esfor&#231;o</p>
                    </list-item>
                  </list>
                </td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">Estenose mitral</td>
                <td align="left" valign="middle">Exerc&#237;cio f&#237;sico (prefer&#237;vel)</td>
                <td align="left" valign="middle">Aumento de gradiente m&#233;dio &gt; 15 mmHg no pico do esfor&#231;o (ou &gt; 18 mmHg com dobutamina)</td>
                <td align="left" valign="middle">Aumento de PSAP &gt; 60 mmHg</td>
                <td align="left" valign="middle">
                  <list list-type="bullet">
                    <list-item>
                      <p>Sintomas</p>
                    </list-item>
                    <list-item>
                      <p>Resposta press&#243;rica PSAP induzida pelo exerc&#237;cio &gt; 60 mmHg</p>
                    </list-item>
                    <list-item>
                      <p>Novas altera&#231;&#245;es da contratilidade segmentar</p>
                    </list-item>
                    <list-item>
                      <p>Queda da FEVE induzida pelo esfor&#231;o</p>
                    </list-item>
                    <list-item>
                      <p>Aumento de gradiente m&#233;dio &gt; 15 mmHg no pico do esfor&#231;o</p>
                    </list-item>
                  </list>
                </td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN10">
              <p>Adaptado de Lancellotti et al.<sup><xref ref-type="bibr" rid="B116">116</xref></sup></p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Deve ser observado o risco de edema agudo de pulm&#227;o e complica&#231;&#245;es hemodin&#226;micas quando esses pacientes s&#227;o submetidos a ecocardiografia de estresse.<sup><xref ref-type="bibr" rid="B118">118</xref></sup></p>
      </sec>
      <sec>
        <title>11.2. Regurgita&#231;&#227;o Mitral</title>
        <p>A principal causa de regurgita&#231;&#227;o mitral (RM) em pa&#237;ses desenvolvidos &#233; a doen&#231;a degenerativa mitral,<sup><xref ref-type="bibr" rid="B119">119</xref></sup> enquanto a febre reum&#225;tica ainda &#233; um fator etiol&#243;gico importante e que impacta a morbidade e mortalidade nos pa&#237;ses em desenvolvimento.<sup><xref ref-type="bibr" rid="B120">120</xref></sup> Diretrizes recentes estabelecem crit&#233;rios de gravidade para a RM,<sup><xref ref-type="bibr" rid="B133">133</xref></sup> com um papel importante para a ecocardiografia na defini&#231;&#227;o do momento ideal para interven&#231;&#227;o, sobretudo em pacientes sintom&#225;ticos, ou em assintom&#225;ticos com remodelamento ventricular significativo, disfun&#231;&#227;o do VE (FEVE &#8804; 60%), fibrila&#231;&#227;o atrial (FA) e/ou hipertens&#227;o pulmonar.<sup><xref ref-type="bibr" rid="B114">114</xref>,<xref ref-type="bibr" rid="B122">122</xref></sup></p>
        <p>A ecocardiografia de estresse tem papel fundamental na avalia&#231;&#227;o dos pacientes com RM, sobretudo em pacientes com discord&#226;ncia entre a cl&#237;nica e os dados ecocardiogr&#225;ficos, como no paciente sintom&#225;tico com RM n&#227;o grave.<sup><xref ref-type="bibr" rid="B123">123</xref></sup> O exame realizado sob esfor&#231;o tem o benef&#237;cio adicional de avaliar a capacidade funcional do paciente, esclarecendo a correla&#231;&#227;o entre sintomas e hemodin&#226;mica assim como a estratifica&#231;&#227;o de risco em pacientes que se referem assintom&#225;ticos com RM grave. Pacientes sintom&#225;ticos com RM aparentemente n&#227;o grave &#224; ecocardiografia basal podem ter mecanismos din&#226;micos que se tornam mais claros durante a ecocardiografia de estresse<sup><xref ref-type="bibr" rid="B124">124</xref></sup>; por esse motivo, a ecocardiografia de estresse pode ser indicada em pacientes sem outra causa aparente de dispneia ao esfor&#231;o portadores de doen&#231;as valvares mitrais, para excluir a presen&#231;a de RM din&#226;mica.</p>
        <p>A ecocardiografia de estresse fornece importantes dados objetivos e pode ser realizada em conjunto com o teste cardiopulmonar, adicionando outras vari&#225;veis de avalia&#231;&#227;o funcional, como o consumo de O<sub>2</sub>.</p>
        <p>Em pacientes com RM prim&#225;ria, os principais dados que podem ser analisados durante a ecocardiografia de estresse s&#227;o a piora da RM sob esfor&#231;o (aumento do ERO &gt; 10 mm), disfun&#231;&#227;o do VD e aumento da PSAP &gt; 60 mmHg<sup><xref ref-type="bibr" rid="B125">125</xref>,<xref ref-type="bibr" rid="B126">126</xref></sup> (<xref ref-type="table" rid="t15">Tabela 11.1</xref>), todos preditores de pior progn&#243;stico. A presen&#231;a de sintomas ou queda da PAS tamb&#233;m s&#227;o indicadores de pior progn&#243;stico.</p>
        <p>Em estudo de Kusunose et al., a presen&#231;a de TAPSE &lt; 1,9 cm ou PSAP &gt; 57 mmHg sob esfor&#231;o foram preditores de evolu&#231;&#227;o para cirurgia valvar mitral em pacientes assintom&#225;ticos com RM grave.<sup><xref ref-type="bibr" rid="B127">127</xref></sup> Al&#233;m disso, a aus&#234;ncia de reserva mioc&#225;rdica tamb&#233;m foi demonstrada como fator de pior progn&#243;stico em pacientes com RM submetidos a ecocardiografia de estresse, como o aumento de FE &#8804;5% ou aumento absoluto de valores de <italic>strain</italic> longitudinal global do VE &#8804; 2%.<sup><xref ref-type="bibr" rid="B128">128</xref>,<xref ref-type="bibr" rid="B129">129</xref></sup></p>
        <p>A ecocardiografia de estresse pode ser utilizada para avalia&#231;&#227;o de pacientes com RM secund&#225;ria, sobretudo quando suspeitamos de componente isqu&#234;mico como mecanismo funcional. Em pacientes com miocardiopatia dilatada n&#227;o isqu&#234;mica, &#233; comum a melhora do grau da RM resultante de mobiliza&#231;&#227;o de reserva contr&#225;til, que &#233; sinal de bom progn&#243;stico, enquanto nos pacientes com cardiomiopatia isqu&#234;mica pode haver piora do grau de RM, o que indica um pior progn&#243;stico.<sup><xref ref-type="bibr" rid="B130">130</xref>,<xref ref-type="bibr" rid="B131">131</xref></sup> Essa piora tamb&#233;m sinaliza a necessidade de abordagem da valva mitral durante a cirurgia de revasculariza&#231;&#227;o mioc&#225;rdica.</p>
        <p>O protocolo de exame sugerido para a ecocardiografia de esfor&#231;o na DVM &#233; apresentado a seguir.</p>
      </sec>
      <sec>
        <title>11.3. Protocolo de Exame &#8211; Ecocardiografia de Esfor&#231;o para Avalia&#231;&#227;o de Les&#227;o Valvar Mitral</title>
        <p>A ecocardiografia de estresse com exerc&#237;cio f&#237;sico pode ser realizada em cicloerg&#244;metro semissupino (ciclomaca), bicicleta ou esteira ergom&#233;trica. O exerc&#237;cio &#233; interrompido quando surgem sintomas limitantes, quando a FC alvo prevista &#233; ultrapassada ou na presen&#231;a de cansa&#231;o ou complica&#231;&#245;es (arritmias, dor precordial t&#237;pica, tontura, queda press&#243;rica). A monitoriza&#231;&#227;o eletrocardiogr&#225;fica e de PA n&#227;o invasiva durante o procedimento &#233; obrigat&#243;ria.</p>
        <p>No exame com cicloerg&#244;metro, &#233; poss&#237;vel come&#231;ar com carga de 25 W, com incremento de 25 W a cada 2-3 minutos. Essa t&#233;cnica permite acompanhar a ecocardiografia de forma cont&#237;nua, avaliando a fun&#231;&#227;o de VD, os par&#226;metros de avalia&#231;&#227;o da les&#227;o valvar (gradientes m&#233;dios, grau da regurgita&#231;&#227;o valvar mitral), a fun&#231;&#227;o do VE e a PSAP. A carga de exerc&#237;cio m&#225;xima obtida &#233; menor em rela&#231;&#227;o &#224;quela obtida em esteira ergom&#233;trica, mas suficiente para a avalia&#231;&#227;o das doen&#231;as valvares em esfor&#231;o.</p>
        <p>No caso da esteira ergom&#233;trica, comumente s&#227;o utilizados os protocolos de Bruce ou Bruce modificado, ou protocolo de rampa, sob supervis&#227;o de profissional habilitado em teste de exerc&#237;cio, interrompido por cansa&#231;o ou poss&#237;veis complica&#231;&#245;es, com aquisi&#231;&#227;o de imagens e dados ecocardiogr&#225;ficos em repouso e ap&#243;s o esfor&#231;o imediato. &#201; preciso tomar cuidado para n&#227;o prolongar em demasiado o exame p&#243;s-esfor&#231;o, que idealmente deve ser realizado em at&#233; 90 segundos para a captura das imagens.</p>
      </sec>
    </sec>
    <sec>
      <title>12. Ecocardiografia de Estresse na Doen&#231;a Valvar A&#243;rtica</title>
      <sec>
        <title>12.1. Estenose A&#243;rtica</title>
        <p>Estenose valvar a&#243;rtica &#233; uma patologia crescente em nosso meio, especialmente devido &#224; degenera&#231;&#227;o valvar senil, devido ao envelhecimento populacional.</p>
        <p>A estenose a&#243;rtica (EAO) importante &#233; definida quando a &#225;rea valvar (AVA) &#233; &#8804; 1,0 cm<sup>2</sup>, e normalmente o gradiente de press&#227;o atrav&#233;s da valva est&#225; correlacionado com o fluxo transvalvar e o orif&#237;cio valvar.<sup><xref ref-type="bibr" rid="B132">132</xref></sup></p>
        <p>Para obter uma avalia&#231;&#227;o valvar completa, &#233; necess&#225;rio avaliar o gradiente e o fluxo transvalvar a&#243;rtico, al&#233;m da AVA em repouso e sob estresse, especialmente quando o fluxo transvalvar est&#225; reduzido, uma vez que se a AVA estiver menor que 1 cm<sup>2</sup> com um gradiente transvalvar elevado em repouso (gradiente m&#233;dio &gt; 40 mmHg) e V<sub>m&#225;x</sub> VE/AO &gt; 4,0 m/s), o diagn&#243;stico de EAO importante j&#225; est&#225; estabelecido.<sup><xref ref-type="bibr" rid="B114">114</xref></sup></p>
        <p>Entre as quatro categorias da estenose a&#243;rtica (alto gradiente; <italic>low-flow, low-gradient</italic> cl&#225;ssica [LFLG]; <italic>low-flow, low-gradient</italic> paradoxal e <italic>normal-flow, low gradient</italic>), a que mais carece da ecocardiografia de estresse &#233; a LFLG cl&#225;ssica, ou seja, com FE reduzida. Um baixo gradiente em repouso na vig&#234;ncia de AVA reduzida n&#227;o exclui EAO grave, que pode ocorrer pela FE estar reduzida, mas outra possibilidade &#233; a EAO de baixo fluxo com FE preservada (paradoxal).</p>
        <p>A ecocardiografia de estresse &#233; indicada de fato nesses casos quando a FE est&#225; reduzida, ou seja, AVA &#8804; 1,0 cm<sup>2</sup>, FE &lt; 50% e gradiente m&#233;dio transvalvar a&#243;rtico &lt; 40 mmHg. Nesses casos, torna-se importante diferenciar a estenose valvar a&#243;rtica fixa verdadeiramente grave da pseudoestenose a&#243;rtica, na qual o problema principal &#233; a cardiomiopatia superestimando a les&#227;o valvar a&#243;rtica devido &#224; abertura inadequada dessa valva, secund&#225;ria ao comprometimento mioc&#225;rdico.<sup><xref ref-type="bibr" rid="B133">133</xref>-<xref ref-type="bibr" rid="B135">135</xref></sup> O protocolo de dobutamina utilizado se encontra na <xref ref-type="fig" rid="f16">Figura 12.1</xref>.</p>
        <fig id="f16">
          <label>Figura 12.1</label>
          <caption>
            <title>Protocolo de dobutamina em baixa dose utilizado na estenose a&#243;rtica low flow-low gradient cl&#225;ssica.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>Na EAO LFLG cl&#225;ssica, a EED em baixa dose &#233; indicada para avaliar a presen&#231;a de reserva contr&#225;til/reserva de fluxo. Quando presente, ela permite avaliar a gravidade da EAO, na qual tr&#234;s padr&#245;es de resposta s&#227;o poss&#237;veis<sup><xref ref-type="bibr" rid="B133">133</xref></sup> (<xref ref-type="fig" rid="f17">Figura 12.2</xref>):</p>
        <list list-type="order">
          <list-item>
            <p>Aumento da reserva de fluxo &#8805; 20% com aumento evidente da AVA para &gt; 1,0 cm<sup>2</sup> e pequeno aumento no gradiente transvalvar, indicando pseudoestenose a&#243;rtica, onde o tratamento cl&#237;nico deve ser recomendado.</p>
          </list-item>
          <list-item>
            <p>Aumento da reserva de fluxo &#8805; 20% sem modifica&#231;&#227;o na AVA, mantendo-se &#8804; 1,0 cm<sup>2</sup>, e aumento do gradiente transvalvar a&#243;rtico (geralmente para gradiente m&#233;dio acima de 40 mmHg), indicando estenose a&#243;rtica grave e fixa, na qual a interven&#231;&#227;o valvar &#233; recomendada.</p>
          </list-item>
          <list-item>
            <p>Quando n&#227;o h&#225; aumento adequado da reserva de fluxo (o volume sist&#243;lico aumenta menos de 20%) e, portanto, os demais par&#226;metros praticamente n&#227;o mudam e a an&#225;lise fica comprometida, o exame &#233; indeterminado. Nesse caso, a tomografia com escore de c&#225;lcio ajuda a estimar a gravidade da EAO. Esse cen&#225;rio ocorre em um ter&#231;o dos pacientes e implica pior progn&#243;stico. Contudo, esse padr&#227;o n&#227;o deve contraindicar a interven&#231;&#227;o valvar, uma vez que muitos pacientes melhoram o desempenho card&#237;aco ap&#243;s a troca valvar.</p>
          </list-item>
        </list>
        <fig id="f17">
          <label>Figura 12.2</label>
          <caption>
            <title>Indica&#231;&#227;o da ecocardiografia de estresse com dobutamina na estenose a&#243;rtica low-flow, low-gradient cl&#225;ssica e as poss&#237;veis respostas do teste de acordo com a presen&#231;a ou aus&#234;ncia de reserva de fluxo. EAO: estenose a&#243;rtica; Dob: dobutamina; FEVE: fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo; AVA: &#225;rea valvar a&#243;rtica; VSi: volume sist&#243;lico indexado; GM: gradiente m&#233;dio.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>Uma sugest&#227;o de Clavel et al.<sup><xref ref-type="bibr" rid="B136">136</xref></sup> para volume sist&#243;lico &lt; 20% durante a EED &#233; calcular a &#225;rea valvar projetada considerando um fluxo normal estimado. Em outras palavras, o fluxo &#233; obtido pelo volume sist&#243;lico/FE e a AVA projetada a uma taxa de fluxo normal que &#233; padronizada como 250 mL/s e pode ser calculada pela seguinte f&#243;rmula: AVA projetada = AVA repouso + (altera&#231;&#227;o AVA/Altera&#231;&#227;o de fluxo) &#215; (250 &#8211; taxa de fluxo), onde AVA projetada &#8804; 1,0 cm<sup>2</sup> indica EAO grave.<sup><xref ref-type="bibr" rid="B136">136</xref>-<xref ref-type="bibr" rid="B138">138</xref></sup> O aumento &gt; 20 bpm &#224; EED, ou a presen&#231;a de arritmias ou hipotens&#227;o arterial deve sinalizar a interrup&#231;&#227;o do teste.</p>
        <p>Para os pacientes com EAO LFLG paradoxal, com FE &#8805; 50%, AVA &#8804; 1,0 cm<sup>2</sup>, gradiente m&#233;dio &lt; 40 mmHg e volume sist&#243;lico indexado &#8804; 35 mL/m<sup>2</sup>, a EED n&#227;o &#233; oficialmente recomendada, dada a limita&#231;&#227;o nas evid&#234;ncias cient&#237;ficas e a possibilidade de hipotens&#227;o arterial importante por risco de gradiente din&#226;mico na VSVE. Tomografia com escore de c&#225;lcio demonstrando valores &#8805; 2000 unidades de Agatston em homens e &#8805; 1200 em mulheres sugere a possibilidade de EAO significativa. Al&#233;m disso, valores &#8805; 3000 em homens e &#8805; 1600 em mulheres confirmam EAO significativa.<sup><xref ref-type="bibr" rid="B137">137</xref></sup></p>
        <p>Para pacientes assintom&#225;ticos com EAO grave de alto gradiente, a ecocardiografia de exerc&#237;cio preferencialmente em ciclomaca tem sido considerada capaz de adicionar valor progn&#243;stico al&#233;m do teste ergom&#233;trico isoladamente.<sup><xref ref-type="bibr" rid="B99">99</xref></sup> A presen&#231;a de um "salto" no gradiente, ou seja, eleva&#231;&#227;o no gradiente transvalvar m&#233;dio &gt; 20 mmHg sob exerc&#237;cio, reflete menor complac&#234;ncia valvar e maior gravidade da les&#227;o.<sup><xref ref-type="bibr" rid="B99">99</xref>,<xref ref-type="bibr" rid="B139">139</xref></sup> Esses pacientes apresentam maior risco de eventos cardiovasculares. Outro achado que &#233; revelado pela ecocardiografia de estresse &#233; o aumento da press&#227;o pulmonar sist&#243;lica &gt; 60 mmHg. Contudo, ainda n&#227;o h&#225; dados robustos para a indica&#231;&#227;o de rotina da ecocardiografia de estresse com exerc&#237;cio nesses pacientes<sup><xref ref-type="bibr" rid="B110">110</xref></sup> (<xref ref-type="fig" rid="f18">Figura 12.3</xref>).</p>
        <fig id="f18">
          <label>Figura 12.3</label>
          <caption>
            <title>Diferentes modalidades de ecocardiografia de estresse e par&#226;metros a serem analisados de acordo com o tipo de les&#227;o valvar a&#243;rtica. EEEx: ecocardiografia de estresse com exerc&#237;cio; EED: ecocardiografia de estresse com dobutamina; RA: regurgita&#231;&#227;o a&#243;rtica; EAO: estenose a&#243;rtica; AVA: &#225;rea valvar a&#243;rtica; Ex: exerc&#237;cio; Ex-GM: gradiente m&#233;dio durante o exerc&#237;cio; DDFVE: di&#226;metro diast&#243;lico final do ventr&#237;culo esquerdo; FEVE: fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo; DSFVE: di&#226;metro sist&#243;lico do ventr&#237;culo esquerdo; IVSF: &#237;ndice de volume sist&#243;lico final do ventr&#237;culo esquerdo; PSAP: press&#227;o sist&#243;lica da art&#233;ria pulmonar.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
      </sec>
      <sec>
        <title>12.2. Insufici&#234;ncia A&#243;rtica</title>
        <p>Na insufici&#234;ncia a&#243;rtica (IAO) grave e cr&#244;nica, o paciente pode ainda estar assintom&#225;tico e evoluir com disfun&#231;&#227;o ventricular latente ou expl&#237;cita, que pode ser irrevers&#237;vel.</p>
        <p>Nesses casos, a ecocardiografia de estresse com exerc&#237;cio ou dobutamina consegue identificar a presen&#231;a ou aus&#234;ncia de reserva contr&#225;til (aumento da FE em pelo menos 5% ou do <italic>strain</italic> longitudinal em valores absolutos &#8805; 2%) ou reserva de fluxo (aumento no volume sist&#243;lico &#8805; 20%) antes da interven&#231;&#227;o. Esse dado &#233; preditor de recupera&#231;&#227;o funcional ap&#243;s troca valvar a&#243;rtica.<sup><xref ref-type="bibr" rid="B110">110</xref>,<xref ref-type="bibr" rid="B140">140</xref></sup></p>
        <p>Principalmente devido ao pequeno n&#250;mero de estudos dispon&#237;veis, A valida&#231;&#227;o da ecocardiografia de estresse para prever resultados nesse subgrupo de pacientes assintom&#225;ticos com IAO grave &#233; limitada.<sup><xref ref-type="bibr" rid="B114">114</xref>,<xref ref-type="bibr" rid="B141">141</xref></sup></p>
      </sec>
    </sec>
    <sec>
      <title>13. Ecocardiograma de Estresse na Cardiomiopatia Dilatada</title>
      <p>A cardiomiopatia dilatada (CMD) &#233; uma doen&#231;a card&#237;aca prim&#225;ria caracterizada por dilata&#231;&#227;o mioc&#225;rdica na aus&#234;ncia de outras etiologias previamente conhecidas e disfun&#231;&#227;o sist&#243;lica. Dado o n&#250;mero crescente de casos diagnosticado, a avalia&#231;&#227;o do estado atual e o progn&#243;stico do paciente se faz cada vez mais importante, pois a evolu&#231;&#227;o no tratamento possibilita o aumento da sobrevida.</p>
      <p>A ecocardiografia de estresse tem se mostrado de grande import&#226;ncia nesse grupo para avalia&#231;&#227;o etiol&#243;gica, diagn&#243;stico e estratifica&#231;&#227;o progn&#243;stica, por meio da an&#225;lise da reserva contr&#225;til; do estado funcional dos pacientes em condi&#231;&#245;es de estresse induzido, daqueles que se beneficiar&#227;o do tratamento com betabloqueadores e da identifica&#231;&#227;o de pacientes com pior progn&#243;stico em termos de morte card&#237;aca e necessidade de transplante.</p>
      <p>Apesar de n&#227;o haver um consenso estabelecido sobre o protocolo, observa-se o uso frequente de dobutamina em altas doses (at&#233; 40 mcg/kg/min) sem o acr&#233;scimo de atropina, principalmente por evocar uma resposta contr&#225;til mais completa e possibilitar a avalia&#231;&#227;o da reserva inotr&#243;pica nesses pacientes. Muitas vezes, a terapia inclui o uso de betabloqueadores, o que diminui a probabilidade de resultados falso-negativos, sem agregar maiores complica&#231;&#245;es.<sup><xref ref-type="bibr" rid="B99">99</xref></sup> Sugere-se que o aumento da contratilidade, expresso pela varia&#231;&#227;o do WMSI no pico da dose de dobutamina e os valores basais, e o aumento &#8805; 5% da FEVE durante a infus&#227;o de dobutamina estejam relacionados a uma melhor taxa de sobrevida, baixa taxa de hospitaliza&#231;&#227;o por insufici&#234;ncia card&#237;aca e aumento da FEVE durante o seguimento. Pacientes com reserva contr&#225;til respondem melhor &#224; terapia com betabloqueador, t&#234;m menor necessidade de transplante e apresentam rela&#231;&#227;o inversa &#224; extens&#227;o de fibrose intersticial.<sup><xref ref-type="bibr" rid="B99">99</xref>,<xref ref-type="bibr" rid="B142">142</xref>-<xref ref-type="bibr" rid="B146">146</xref></sup> Entretanto, a aus&#234;ncia de reserva contr&#225;til em pacientes com FEVE preservada ou reduzida com frequ&#234;ncia est&#225; associada a RFC limitado, sendo portanto, um marcador de disfun&#231;&#227;o sist&#243;lica latente do VE e cardiomiopatia subcl&#237;nica.<sup><xref ref-type="bibr" rid="B99">99</xref></sup></p>
      <p>O evento adverso associado com mais frequ&#234;ncia a altas doses do medicamento &#233; a arritmia ventricular complexa (extrass&#237;stole ventricular multifocal em 6,4% e taquicardia ventricular n&#227;o sustentada em 1,6%), geralmente associados a pacientes com hipocalemia.<sup><xref ref-type="bibr" rid="B142">142</xref>,<xref ref-type="bibr" rid="B143">143</xref></sup></p>
      <p>O protocolo com vasodilatador (dipiridamol 0,84 mg por 10 min), com acr&#233;scimo do <italic>handgrip</italic> no pico de sua infus&#227;o (aumentando a sensibilidade do teste), raramente &#233; utilizado para avaliar reserva contr&#225;til, mas tem sido proposto como alternativa &#224; dobutamina por ser menos arritmog&#234;nico, melhor tolerado e apresentar informa&#231;&#245;es progn&#243;sticas semelhantes aos pacientes com doen&#231;a isqu&#234;mica. Al&#233;m de n&#227;o ter a influ&#234;ncia do uso de betabloquedor<sup><xref ref-type="bibr" rid="B147">147</xref></sup> para a an&#225;lise espec&#237;fica de reserva contr&#225;til, contudo, n&#227;o ganhou grande repercuss&#227;o na pr&#225;tica cl&#237;nica para essa indica&#231;&#227;o em compara&#231;&#227;o com a dobutamina.<sup><xref ref-type="bibr" rid="B49">49</xref>,<xref ref-type="bibr" rid="B148">148</xref>-<xref ref-type="bibr" rid="B150">150</xref></sup></p>
      <p>As <xref ref-type="table" rid="t16">Tabelas 13.1</xref>, <xref ref-type="table" rid="t17">13.2</xref>, <xref ref-type="table" rid="t18">13.3</xref>, <xref ref-type="table" rid="t19">13.4</xref> e <xref ref-type="table" rid="t20">13.5</xref> apresentam as recomenda&#231;&#245;es a serem realizadas junto &#224; ecocardiografia de estresse na CMD.</p>
      <table-wrap id="t16">
        <label>Tabela 13.1</label>
        <caption>
          <title>Par&#226;metros a avaliar na ecocardiografia de estresse na cardiomiopatia dilatada</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup width="50%">
            <col/>
            <col/>
          </colgroup>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr style="background-color:#76B4CF">
              <td align="left" valign="middle" colspan="2">
                <bold>1. O que avaliar na ecocardiografia de estresse na cardiomiopatia dilatada?</bold>
              </td>
            </tr>
            <tr>
              <td align="left" valign="middle">- Reserva contr&#225;til</td>
              <td align="left" valign="middle">- Reserva diast&#243;lica</td>
            </tr>
            <tr>
              <td align="left" valign="middle">- Isquemia estresse induzida</td>
              <td align="left" valign="middle">- Regurgita&#231;&#227;o mitral din&#226;mica</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">- Varia&#231;&#227;o na PSAP</td>
              <td align="left" valign="middle">- Congest&#227;o pulmonar (linha B)</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <table-wrap id="t17">
        <label>Tabela 13.2</label>
        <caption>
          <title>Par&#226;metros a medir na ecocardiografia de estresse na cardiomiopatia dilatada</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup width="100%">
            <col/>
          </colgroup>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr style="background-color:#76B4CF">
              <td align="left" valign="middle">
                <bold>2. O que medir?</bold>
              </td>
            </tr>
            <tr>
              <td align="left" valign="middle">- Ondas E e A</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">- e&#180;(Doppler PW)</td>
            </tr>
            <tr>
              <td align="left" valign="middle">- Regurgita&#231;&#227;o mitral e tric&#250;spide (Doppler CW)</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <table-wrap id="t18">
        <label>Tabela 13.3</label>
        <caption>
          <title>Momentos do teste para aferi&#231;&#245;es na cardiomiopatia dilatada</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup width="100%">
            <col/>
          </colgroup>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr style="background-color:#76B4CF">
              <td align="left" valign="middle">
                <bold>3. Quando medir (protocolo dobutamina)?</bold>
              </td>
            </tr>
            <tr>
              <td align="left" valign="middle">- Basal - Baixa dose - Pico da infus&#227;o da medica&#231;&#227;o</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <table-wrap id="t19">
        <label>Tabela 13.4</label>
        <caption>
          <title>Respostas esperadas na ecocardiografia de estresse na cardiomiopatia dilatada</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup width="100%">
            <col/>
          </colgroup>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr style="background-color:#76B4CF">
              <td align="left" valign="middle">
                <bold>4. Respostas esperadas:</bold>
              </td>
            </tr>
            <tr>
              <td align="left" valign="middle">- Aumento ou n&#227;o da contratilidade do VE</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">- Redu&#231;&#227;o ou aumento da regurgita&#231;&#227;o mitral</td>
            </tr>
            <tr>
              <td align="left" valign="middle">- Varia&#231;&#245;es da PSAP e rela&#231;&#227;o E/e&#8217;</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">- Presen&#231;a ou aus&#234;ncia de linhas B nos campos pulmonares</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <table-wrap id="t20">
        <label>Tabela 13.5</label>
        <caption>
          <title>Protocolos utilizados (A-dobutamina e B-dipiridamol) na ecocardiografia de estresse na cardiomiopatia dilatada</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup width="100%">
            <col/>
          </colgroup>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr style="background-color:#76B4CF">
              <td align="left" valign="middle"><bold>5. Protocolos utilizados</bold> (<xref ref-type="fig" rid="f19">Figura 12.4</xref>).</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <fig id="f19">
        <label>Figura 12.4</label>
        <caption>
          <title>Protocolos utilizados (A: dobutamina e B: dipiridamol) na ecocardiografia de estresse na cardiomiopatia dilatada.</title>
        </caption>
        <graphic xlink:href=""/>
      </fig>
    </sec>
    <sec>
      <title>14. Ecocardiografia de Estresse na Cardiomiopatia Chag&#225;sica</title>
      <p>Pacientes com cardiopatia cr&#244;nica da doen&#231;a de Chagas (CCDC) frequentemente manifestam dor tor&#225;cica at&#237;pica e apresentam anormalidades eletrocardiogr&#225;ficas, tais como altera&#231;&#245;es no segmento ST e ondas Q patol&#243;gicas, al&#233;m de dist&#250;rbios regionais de contratilidade e de perfus&#227;o mioc&#225;rdica que simulam a apresenta&#231;&#227;o da doen&#231;a coron&#225;ria ateroscler&#243;tica.<sup><xref ref-type="bibr" rid="B151">151</xref></sup></p>
      <p>At&#233; poucas d&#233;cadas atr&#225;s, os pacientes com doen&#231;a de Chagas eram predominantemente trabalhadores rurais, com baixo perfil de risco para doen&#231;a obstrutiva coron&#225;ria. Com a urbaniza&#231;&#227;o crescente dessa popula&#231;&#227;o, a partir principalmente de 1980, eles passaram a ser expostos aos mesmos fatores de risco para doen&#231;a ateroscler&#243;tica que os indiv&#237;duos n&#227;o infectados pelo <italic>Trypanosoma cruzi</italic>.<sup><xref ref-type="bibr" rid="B152">152</xref></sup> Entretanto, na maioria dos casos, a avalia&#231;&#227;o das coron&#225;rias epic&#225;rdicas revela a aus&#234;ncia de obstru&#231;&#227;o ateroscler&#243;tica subepic&#225;rdica significativa, com tais modifica&#231;&#245;es atribu&#237;das &#224; disfun&#231;&#227;o microvascular coronariana.<sup><xref ref-type="bibr" rid="B153">153</xref></sup></p>
      <p>Alguns estudos avaliaram a aplicabilidade da ecocardiografia de estresse na doen&#231;a de Chagas. A isquemia microvascular &#233; considerada um dist&#250;rbio precoce na evolu&#231;&#227;o da doen&#231;a, precedendo a disfun&#231;&#227;o ventricular regional e possivelmente relacionada &#224; indu&#231;&#227;o de hiberna&#231;&#227;o ou atordoamento mioc&#225;rdico. Resultados obtidos por estudo de ecocardiografia de estresse utilizando vasodilatador (dipiridamol) demonstram diminui&#231;&#227;o da reserva vasodilatadora coron&#225;ria, um &#237;ndice de disfun&#231;&#227;o microvascular, em pacientes com a forma indeterminada da doen&#231;a em compara&#231;&#227;o com controles normais.<sup><xref ref-type="bibr" rid="B154">154</xref></sup></p>
      <p>Quanto &#224; resposta cronotr&#243;pica, a ecocardiografia com dobutamina demonstra que pacientes com doen&#231;a de Chagas apresentam uma menor resposta inotr&#243;pica e cronotr&#243;pica quando comparados a um grupo controle. Al&#233;m disso, a ecocardiografia de estresse farmacol&#243;gico pode demonstrar a presen&#231;a de reserva contr&#225;til bif&#225;sica nesses pacientes, apesar da aus&#234;ncia de doen&#231;a coron&#225;ria epic&#225;rdica.<sup><xref ref-type="bibr" rid="B155">155</xref></sup></p>
      <p>Em rela&#231;&#227;o ao valor preditor para a evolu&#231;&#227;o da cardiopatia, a presen&#231;a de arritmias ventriculares complexas na EEF foi um preditor independente de evolu&#231;&#227;o da doen&#231;a em um grupo de pacientes na fase inicial da cardiopatia.<sup><xref ref-type="bibr" rid="B156">156</xref></sup></p>
      <p>Por fim, no que se refere ao emprego da dobutamina em uma cardiopatia arritmog&#234;nica, a ecocardiografia de estresse farmacol&#243;gico evidenciou seguran&#231;a na cardiopatia chag&#225;sica em uma coorte de pacientes em investiga&#231;&#227;o para doen&#231;a coron&#225;ria. A presen&#231;a do &#237;ndice de contra&#231;&#227;o segmentar alterado em repouso foi um preditor independente para o surgimento de arritmias complexas durante o exame.<sup><xref ref-type="bibr" rid="B157">157</xref></sup></p>
    </sec>
    <sec>
      <title>15. Ecocardiografia de Estresse na Cardiomiopatia Hipertr&#243;fica</title>
      <p>A CMH &#233; uma doen&#231;a cardiovascular gen&#233;tica comum com padr&#227;o autoss&#244;mico dominante e distribui&#231;&#227;o igual por sexo. A preval&#234;ncia varia com a idade, estado subcl&#237;nico ou cl&#237;nico e diferen&#231;as raciais.<sup><xref ref-type="bibr" rid="B158">158</xref></sup> A suspeita cl&#237;nica pode surgir pela manifesta&#231;&#227;o de sintomas, detec&#231;&#227;o de sopro card&#237;aco, padr&#227;o eletrocardiogr&#225;fico anormal ou um evento card&#237;aco. Al&#233;m disso, pode ser um achado incidental durante a realiza&#231;&#227;o de ecocardiografia por outras indica&#231;&#245;es.<sup><xref ref-type="bibr" rid="B159">159</xref></sup></p>
      <p>A ecocardiografia desempenha um papel muito importante na confirma&#231;&#227;o do diagn&#243;stico, determina&#231;&#227;o do padr&#227;o de hipertrofia, avalia&#231;&#227;o da obstru&#231;&#227;o da VSVE, movimenta&#231;&#227;o anterior sist&#243;lico (MAS) da valva mitral e regurgita&#231;&#227;o mitral (RM), bem como na avalia&#231;&#227;o da fun&#231;&#227;o sist&#243;lica e diast&#243;lica do VE, do volume atrial esquerdo e da press&#227;o pulmonar.<sup><xref ref-type="bibr" rid="B160">160</xref></sup></p>
      <p>A EEF &#233; amplamente utilizada para medir a obstru&#231;&#227;o da VSVE din&#226;mica e indut&#237;vel em pacientes sintom&#225;ticos com gradiente de pico da VSVE em repouso &lt; 50 mmHg, para detectar RM e para monitorar a resposta ao tratamento. A import&#226;ncia dos gradientes &gt; 50 mmHg, seja em repouso ou p&#243;s-esfor&#231;o, reside no fato de haver um limite convencional para interven&#231;&#227;o invasiva quando os sintomas n&#227;o est&#227;o sob controle com farmacoterapia.<sup><xref ref-type="bibr" rid="B158">158</xref></sup> O estresse sob exerc&#237;cio &#233; o mais recomendado nesses casos.</p>
      <p>A EEF pode ser realizada em ciclomaca semissupina, em bicicleta ou esteira. Sugere-se que a esteira provoca maior gradiente de VSVE. A escolha do protocolo deve considerar o estado geral do paciente, a experi&#234;ncia do m&#233;dico e os recursos da institui&#231;&#227;o.</p>
      <p>Antes do teste, &#233; importante estar ciente das condi&#231;&#245;es do paciente (classe funcional, estado de hidrata&#231;&#227;o, hor&#225;rio de alimenta&#231;&#227;o, bebidas alco&#243;licas, etc.) e dos fatores farmacol&#243;gicos (vasodilatadores, diur&#233;ticos), pois podem influenciar o andamento do exame. Ao contr&#225;rio de outras modalidades de estresse, os betabloqueadores n&#227;o devem ser retirados antes do exerc&#237;cio para esse tipo de avalia&#231;&#227;o.</p>
      <p>Os ARUS s&#227;o &#250;teis na confirma&#231;&#227;o de hipertrofia septal e apical, na detec&#231;&#227;o de trombos apicais e na exclus&#227;o de aneurismas apicais.<sup><xref ref-type="bibr" rid="B161">161</xref></sup></p>
      <p>&#201; fundamental orientar o paciente sobre o objetivo do estudo e poss&#237;veis eventos. Como um dos objetivos da ecocardiografia de estresse &#233; quantificar o gradiente da VSVE em pacientes sintom&#225;ticos sem gradiente ou com gradiente baixo em repouso, recomenda-se medir o gradiente com a maior frequ&#234;ncia poss&#237;vel durante o exame. Al&#233;m disso, &#233; preciso avaliar SAM, RM, anormalidades de movimento da parede do VE e disfun&#231;&#227;o diast&#243;lica.</p>
      <p>As altera&#231;&#245;es eletrocardiogr&#225;ficas devem ser monitoradas. Os par&#226;metros cl&#237;nicos e ecocardiogr&#225;ficos s&#227;o avaliados durante o exerc&#237;cio e na fase de recupera&#231;&#227;o precoce e tardia, enquanto a pr&#233;-carga diminui gradativamente. Se a EEF n&#227;o provocar um aumento significativo no gradiente da VSVE, a avalia&#231;&#227;o do gradiente no ortostatismo p&#243;s-exerc&#237;cio deve ser considerada. Resposta hipertensiva, redu&#231;&#227;o da PA superior a 10 mmHg em compara&#231;&#227;o com a PA de repouso antes do exame, dispneia, desconforto tor&#225;cico e taquiarritmia sustentada s&#227;o indica&#231;&#245;es para interrup&#231;&#227;o do exame.<sup><xref ref-type="bibr" rid="B162">162</xref></sup> A obstru&#231;&#227;o da VSVE com baixa carga de exerc&#237;cio est&#225; correlacionada com uma baixa capacidade funcional. A obstru&#231;&#227;o da VSVE &#233; um fator de risco para morte s&#250;bita e eventos cardiovasculares graves.<sup><xref ref-type="bibr" rid="B163">163</xref></sup></p>
      <p>Como a ecocardiografia de estresse &#233; uma t&#233;cnica que depende da experi&#234;ncia do operador, uma curva de aprendizado supervisionada &#233; imprescind&#237;vel para desenvolver experi&#234;ncia na avalia&#231;&#227;o de CMH, a fim de obter resultados confi&#225;veis e reprodut&#237;veis que permitam a tomada de decis&#245;es sobre o manejo e seguimento dos pacientes. Sabe-se que o curso cl&#237;nico da CMH &#233; heterog&#234;neo e imprevis&#237;vel. A ecocardiografia de estresse tem o potencial de diferenciar a CMH n&#227;o obstrutiva das formas com gradiente din&#226;mico e, aliada &#224; capacidade de exerc&#237;cio, &#224; PA e &#224; resposta da FC, prever o desenvolvimento futuro de insufici&#234;ncia card&#237;aca de modo a direcionar as atuais estrat&#233;gias de manejo dispon&#237;veis de acordo com cada paciente no contexto dessa doen&#231;a gen&#233;tica complexa. Procedimentos como miectomia septal cir&#250;rgica e abla&#231;&#227;o septal percut&#226;nea com &#225;lcool s&#227;o considerados indica&#231;&#245;es Classe I para pacientes sintom&#225;ticos com gradiente em VSVE em repouso e aqueles sem resposta aceit&#225;vel &#224; terapia farmacol&#243;gica.<sup><xref ref-type="bibr" rid="B164">164</xref></sup></p>
    </sec>
    <sec>
      <title>16. Ecocardiografia de Estresse na Avalia&#231;&#227;o da Fun&#231;&#227;o do Ventr&#237;culo Direito e na Hipertens&#227;o Pulmonar</title>
      <p>A hipertens&#227;o pulmonar (HP) &#233; um dist&#250;rbio fisiopatol&#243;gico que pode envolver diversas condi&#231;&#245;es cl&#237;nicas e estar associada a in&#250;meras doen&#231;as respirat&#243;rias e/ou cardiovasculares. Independentemente do processo fisiopatol&#243;gico subjacente e do local das altera&#231;&#245;es funcionais, a HP &#233; definida como uma PA pulmonar m&#233;dia de repouso (PAPm) de &gt; 20 mmHg medida por cateterismo card&#237;aco direito (CCD).<sup><xref ref-type="bibr" rid="B165">165</xref></sup></p>
      <p>Recentemente, tem crescido o interesse pela sua aplica&#231;&#227;o na detec&#231;&#227;o e avalia&#231;&#227;o da gravidade da HP e disfun&#231;&#227;o card&#237;aca direita.<sup><xref ref-type="bibr" rid="B166">166</xref>,<xref ref-type="bibr" rid="B167">167</xref></sup></p>
      <p>O CCD &#233; o padr&#227;o-ouro para avaliar a hemodin&#226;mica pulmonar e possibilita diagnosticar e classificar a HP. De acordo com o consenso atual, o CCD de exerc&#237;cio &#233; o m&#233;todo recomendado para avaliar a hemodin&#226;mica cardiopulmonar. No entanto, ele acarreta alguns desafios t&#233;cnicos, exigindo profissionais experientes, equipamentos especiais e tempo adicional de procedimento.<sup><xref ref-type="bibr" rid="B165">165</xref></sup></p>
      <p>A ecocardiografia de estresse da circula&#231;&#227;o pulmonar e do ventr&#237;culo direito (VD) revela diferen&#231;as relevantes do ponto de vista progn&#243;stico entre indiv&#237;duos saud&#225;veis, atletas, residentes de altitude e pacientes com diversas condi&#231;&#245;es cardiorrespirat&#243;rias, podendo avaliar a circula&#231;&#227;o pulmonar e o comportamento do ventr&#237;culo direito nesses indiv&#237;duos, al&#233;m de auxiliar no diagn&#243;stico de HP latente ou evidente, com ou sem altera&#231;&#227;o da fun&#231;&#227;o do VD, adaptando-se ao aumento da carga.<sup><xref ref-type="bibr" rid="B168">168</xref></sup></p>
      <p>Semelhante ao conceito de CCD de exerc&#237;cio, a complementa&#231;&#227;o com um teste de estresse &#224; ecocardiografia Doppler padr&#227;o pode melhorar a acur&#225;cia diagn&#243;stica para detectar HP p&#243;s-capilar. Al&#233;m disso, a ecocardiografia de estresse f&#237;sico agrega valor no manejo de pacientes com HP, pois tamb&#233;m nos permite avaliar a mec&#226;nica complexa do VD (por exemplo, reserva contr&#225;til) e a capacidade da vasculatura pulmonar de acomodar o fluxo aumentado.<sup><xref ref-type="bibr" rid="B168">168</xref></sup></p>
      <p>As medidas ecocardiogr&#225;ficas da fun&#231;&#227;o do VD que s&#227;o preditores independentes de mortalidade na HP incluem a excurs&#227;o sist&#243;lica no plano anular tric&#250;spide (TAPSE &lt; 18 mm),<sup><xref ref-type="bibr" rid="B169">169</xref>-<xref ref-type="bibr" rid="B173">173</xref></sup> a mudan&#231;a de &#225;rea fracionada do VD (FAC &lt; 35%, a velocidade anular lateral do pico sist&#243;lico tric&#250;spide (S&#8217; &lt; 9,7 cm/s<sup><xref ref-type="bibr" rid="B174">174</xref></sup>) e o &#237;ndice de Tei (&gt; 0,40 pelo Doppler puls&#225;til ou &gt; 0,55 pelo Doppler tecidual<sup><xref ref-type="bibr" rid="B175">175</xref></sup>).</p>
      <p>Todas as m&#233;tricas descritas acima podem ser avaliadas em repouso e ap&#243;s o pico de estresse (exerc&#237;cio ou com ecocardiografia com dobutamina). A maioria dos dados at&#233; o momento foi derivada de volunt&#225;rios saud&#225;veis, mas v&#225;rios estudos de pequeno e m&#233;dio porte avaliam o papel progn&#243;stico da reserva contr&#225;til do VD em pacientes com HP, doen&#231;a valvar e insufici&#234;ncia card&#237;aca.<sup><xref ref-type="bibr" rid="B176">176</xref></sup></p>
      <p>N&#227;o se sabe se a avalia&#231;&#227;o ecocardiogr&#225;fica n&#227;o invasiva &#233; igualmente confi&#225;vel e geralmente vi&#225;vel para definir condi&#231;&#245;es de doen&#231;a com ou em risco de HP. Limita&#231;&#245;es semelhantes se aplicam &#224; avalia&#231;&#227;o ecocardiogr&#225;fica da fun&#231;&#227;o do VD durante o exerc&#237;cio.<sup><xref ref-type="bibr" rid="B167">167</xref>,<xref ref-type="bibr" rid="B176">176</xref></sup></p>
      <p>Uma medida poss&#237;vel e n&#227;o invasiva da reserva contr&#225;til do VD por meio da ecocardiografia de estresse f&#237;sico foi proposta por Gr&#252;nig et al., que demonstraram que um aumento da PA pulmonar (PAP) induzido pelo exerc&#237;cio foi uma medida da reserva contr&#225;til do VD e fator progn&#243;stico independente em pacientes com HP pr&#233;-capilar.<sup><xref ref-type="bibr" rid="B177">177</xref></sup></p>
    </sec>
    <sec>
      <title>17. Ecocardiografia de Estresse na Avalia&#231;&#227;o P&#243;s-COVID-19</title>
      <p>A maioria das publica&#231;&#245;es a respeito das manifesta&#231;&#245;es cardiovasculares da COVID-19 avalia a fase aguda da infec&#231;&#227;o, onde se demonstrou que a presen&#231;a de disfun&#231;&#227;o card&#237;aca detectada &#224; ecocardiografia de repouso estava associada a pior progn&#243;stico em pacientes com COVID-19 grave.<sup><xref ref-type="bibr" rid="B178">178</xref></sup> Pelo alto risco da contamina&#231;&#227;o cruzada por got&#237;culas, o uso da EEF foi adiado ou cancelado durante a pandemia.<sup><xref ref-type="bibr" rid="B179">179</xref>,<xref ref-type="bibr" rid="B180">180</xref></sup> Em pacientes de baixo risco para COVID-19 nos quais a indica&#231;&#227;o era apropriada e o adiamento n&#227;o era poss&#237;vel, deu-se prefer&#234;ncia &#224; ecocardiografia de estresse farmacol&#243;gico.<sup><xref ref-type="bibr" rid="B179">179</xref>,<xref ref-type="bibr" rid="B180">180</xref></sup></p>
      <p>Ap&#243;s o fim do estado de emerg&#234;ncia da pandemia, diversos estudos tentaram descrever as consequ&#234;ncias da COVID-19 para o sistema cardiovascular no longo prazo, mas a maioria ainda empregou apenas a ecocardiografia de repouso. Posteriormente, algumas poucas publica&#231;&#245;es exploraram o uso da ecocardiografia de estresse como ferramenta para a avalia&#231;&#227;o de pacientes ap&#243;s a recupera&#231;&#227;o da infec&#231;&#227;o por SARS-CoV-2. Um estudo prospectivo em 174 atletas jovens com fun&#231;&#227;o ventricular normal ao repouso ap&#243;s COVID-19 visou identificar envolvimento mioc&#225;rdico por meio de um amplo protocolo funcional que inclu&#237;a EEF.<sup><xref ref-type="bibr" rid="B181">181</xref></sup> Sinais de envolvimento mioc&#225;rdico foram encontrados em cinco atletas (2,9%), tr&#234;s dos quais mostraram altera&#231;&#245;es clinicamente significativas ao esfor&#231;o, incluindo arritmia ventricular em dois e altera&#231;&#227;o da contratilidade segmentar em um indiv&#237;duo.<sup><xref ref-type="bibr" rid="B181">181</xref></sup> Embora raro, o comprometimento mioc&#225;rdico s&#243; foi detectado durante o esfor&#231;o, sugerindo que a triagem com EEF pode ser &#250;til em casos selecionados para a orienta&#231;&#227;o ao retorno da atividade atl&#233;tica competitiva ap&#243;s infec&#231;&#227;o por SARS-CoV-2. Outro estudo avaliou 71 pacientes recuperando-se da COVID-19, a maioria sintom&#225;ticos, por meio de um protocolo que combinava EEF e teste cardiopulmonar.<sup><xref ref-type="bibr" rid="B182">182</xref></sup> O consumo de oxig&#234;nio (VO<sub>2</sub>) no pico foi menor em pacientes p&#243;s COVID-19 em compara&#231;&#227;o com o grupo controle devido a uma combina&#231;&#227;o de incompet&#234;ncia cronotr&#243;pica e reserva atenuada do volume sist&#243;lico do VE (aumento insuficiente do <italic>stroke volume</italic> durante o esfor&#231;o).<sup><xref ref-type="bibr" rid="B182">182</xref></sup> Esses estudos ressaltam a import&#226;ncia de avaliar a fun&#231;&#227;o card&#237;aca em repouso e tamb&#233;m em situa&#231;&#245;es de estresse, como o exerc&#237;cio, para compreender completamente o impacto da infec&#231;&#227;o por SARS-CoV-2 no cora&#231;&#227;o. Investiga&#231;&#245;es em andamento poder&#227;o, por meio da utiliza&#231;&#227;o da ecocardiografia de estresse, nos ajudar a entender melhor a rela&#231;&#227;o entre a hist&#243;ria de infec&#231;&#227;o por SARS-CoV-2, suas implica&#231;&#245;es cardiovasculares e a atividade f&#237;sica.<sup><xref ref-type="bibr" rid="B183">183</xref></sup></p>
      <p>Men&#231;&#227;o especial deve ser feita ao uso de ARUS, ferramentas indispens&#225;veis para a pr&#225;tica moderna da ecocardiografia de estresse. Ap&#243;s dezembro de 2020, coincidente com o in&#237;cio da vacina&#231;&#227;o contra COVID-19 na popula&#231;&#227;o americana, observou-se um aumento das rea&#231;&#245;es adversas graves aos ARUS contendo polietilenoglicol (PEG) em sua composi&#231;&#227;o, como Sonovue ou Lumason (Bracco Diagnostics) e Definity (Lantheus Medical Imaging). Cogitou-se como substrato a possibilidade de reatividade cruzada entre esses ARUS e as vacinas de COVID-19 baseadas em RNA mensageiro (Pfizer/BioNTec e Moderna), uma vez que ambos os grupos de f&#225;rmacos cont&#234;m PEG.<sup><xref ref-type="bibr" rid="B184">184</xref></sup> Um estudo retrospectivo caso-controle apontou que indiv&#237;duos com rea&#231;&#245;es adversas graves ao Lumason ocorridas desde mar&#231;o de 2021 nos EUA tinham sido vacinados para COVID-19 mais frequentemente do que aqueles sem rea&#231;&#245;es adversas.<sup><xref ref-type="bibr" rid="B185">185</xref></sup></p>
    </sec>
    <sec>
      <title>18. Ecocardiografia de Estresse e Reserva de Fluxo Coronariano nos Vasos Nativos</title>
      <p>A RFC pode ser avaliada por meio da an&#225;lise direta do fluxo da art&#233;ria durante a ecocardiografia de estresse. <italic>Presets</italic> espec&#237;ficos permitem visualizar, sem uso de microbolhas, a ADA durante a ecocardiografia de estresse com adenosina, dipiridamol ou mesmo com dobutamina, em pelo menos 90% dos casos, com menor taxa de sucesso na descendente posterior (DP) e circunflexa (CX), particularmente na EEF.<sup><xref ref-type="bibr" rid="B23">23</xref>,<xref ref-type="bibr" rid="B186">186</xref>-<xref ref-type="bibr" rid="B189">189</xref></sup></p>
      <p>O c&#225;lculo da RFC consiste na divis&#227;o da velocidade diast&#243;lica obtida na hiperemia pela velocidade diast&#243;lica registrada em repouso (<xref ref-type="fig" rid="f20">Figura 18.1</xref>). Na correla&#231;&#227;o entre a RFC obtida na ecocardiografia de estresse e o percentual de estenose coronariana, RFC &#8805; 2 indica normalidade, compat&#237;vel com bom progn&#243;stico. A RFC pode estar reduzida (&lt; 2) por estenose coronariana e/ou microcircula&#231;&#227;o comprometida, sendo preditor independente de desfecho adverso. Valores mais baixos da RFC s&#227;o mais indicativos de estenose coronariana importante (<xref ref-type="table" rid="t21">Tabela 18.1</xref>).<sup><xref ref-type="bibr" rid="B187">187</xref>,<xref ref-type="bibr" rid="B190">190</xref>-<xref ref-type="bibr" rid="B194">194</xref></sup></p>
      <fig id="f20">
        <label>Figura 18.1</label>
        <caption>
          <title>Obten&#231;&#227;o da RFC basal normal na art&#233;ria descendente anterior e que aumenta significativamente (RFC = 3,3) com 30 mcg/kg/min de dobutamina. ADA: art&#233;ria coron&#225;ria descendente anterior; EED: ecocardiografia de estresse com dobutamina; FC: frequ&#234;ncia card&#237;aca; PVD: pico de velocidade diast&#243;lica; RFC (reserva de fluxo coronariano) = PVD no estresse <bold>/</bold> PVD basal. RFC normal (&#8805; 2) e precoce obtido antes de alcan&#231;ar a FC alvo do exame, registrado em est&#225;gios intermedi&#225;rios do EED.</title>
        </caption>
        <graphic xlink:href=""/>
      </fig>
      <table-wrap id="t21">
        <label>Tabela 18.1</label>
        <caption>
          <title>Correla&#231;&#227;o entre reserva de fluxo coronariano e percentual de estenose coronariana</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup width="13%">
            <col/>
            <col/>
            <col/>
            <col/>
            <col/>
            <col/>
            <col/>
            <col/>
          </colgroup>
          <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
            <tr style="background-color:#76B4CF">
              <th align="left" valign="middle">Autores</th>
              <th align="center" valign="middle">N&#186; casos</th>
              <th align="center" valign="middle">RFC (cut off)</th>
              <th align="center" valign="middle">Estressor</th>
              <th align="center" valign="middle">% Estenose</th>
              <th align="center" valign="middle">Sensibilidade</th>
              <th align="center" valign="middle">Especificidade</th>
              <th align="center" valign="middle">Acur&#225;cia</th>
            </tr>
          </thead>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr>
              <td align="left" valign="middle">Nohtomi et al.<sup><xref ref-type="bibr" rid="B187">187</xref></sup></td>
              <td align="center" valign="middle">110 ADA</td>
              <td align="center" valign="middle">&lt; 2</td>
              <td align="center" valign="middle">Dipiridamol</td>
              <td align="center" valign="middle">&gt; 50%</td>
              <td align="center" valign="middle">94%</td>
              <td align="center" valign="middle">65%</td>
              <td align="center" valign="middle">81%</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle" rowspan="3">Voci et al.<sup><xref ref-type="bibr" rid="B190">190</xref></sup></td>
              <td align="center" valign="middle">44 (ADA+DP)</td>
              <td align="center" valign="middle">&lt; 2</td>
              <td align="center" valign="middle">Adenosina</td>
              <td align="center" valign="middle">&#8805; 70%</td>
              <td align="center" valign="middle">89%</td>
              <td align="center" valign="middle">96%</td>
              <td align="center" valign="middle">93%</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">18 DP</td>
              <td align="center" valign="middle">1,4 &#177; 0,54</td>
              <td align="center" valign="middle"/>
              <td align="center" valign="middle">&#8805; 70%</td>
              <td align="center" valign="middle">89%</td>
              <td align="center" valign="middle">91%</td>
              <td align="center" valign="middle">93%</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">19 ADA</td>
              <td align="center" valign="middle">1,12 &#177; 0,49</td>
              <td align="center" valign="middle"/>
              <td align="center" valign="middle">&#8805; 70%</td>
              <td align="center" valign="middle">89%</td>
              <td align="center" valign="middle">100%</td>
              <td align="center" valign="middle">95%</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Lowenstein et al.<sup><xref ref-type="bibr" rid="B191">191</xref></sup></td>
              <td align="center" valign="middle">132 ADA</td>
              <td align="center" valign="middle">&lt; 2</td>
              <td align="center" valign="middle">Dipiridamol</td>
              <td align="center" valign="middle">&gt; 70%</td>
              <td align="center" valign="middle">87%</td>
              <td align="center" valign="middle">73%</td>
              <td align="center" valign="middle">80%</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle" rowspan="2">Matsumara et al.<sup><xref ref-type="bibr" rid="B192">192</xref></sup></td>
              <td align="center" valign="middle">138 ADA</td>
              <td align="center" valign="middle">-</td>
              <td align="center" valign="middle">Adenosina</td>
              <td align="center" valign="middle"/>
              <td align="center" valign="middle"/>
              <td align="center" valign="middle"/>
              <td align="center" valign="middle" rowspan="2"/>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">30 ADA</td>
              <td align="center" valign="middle">&lt; 2</td>
              <td align="center" valign="middle"/>
              <td align="center" valign="middle">&#8805; 70%</td>
              <td align="center" valign="middle">90%</td>
              <td align="center" valign="middle">93%</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Soylu et al.<sup><xref ref-type="bibr" rid="B193">193</xref></sup></td>
              <td align="center" valign="middle">44 ADA</td>
              <td align="center" valign="middle">&lt; 1,6</td>
              <td align="center" valign="middle">Dipiridamol</td>
              <td align="center" valign="middle">&#8805; 55%</td>
              <td align="center" valign="middle">100%</td>
              <td align="center" valign="middle">94%</td>
              <td align="center" valign="middle"/>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle" rowspan="4">Hyodo et al.<sup><xref ref-type="bibr" rid="B194">194</xref></sup></td>
              <td align="center" valign="middle">175 art&#233;rias</td>
              <td align="center" valign="middle">-</td>
              <td align="center" valign="middle">Adenosina</td>
              <td align="center" valign="middle">&gt; 50%</td>
              <td align="center" valign="middle"/>
              <td align="center" valign="middle"/>
              <td align="center" valign="middle" rowspan="4"/>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">166 ADA</td>
              <td align="center" valign="middle">&lt; 2</td>
              <td align="center" valign="middle"/>
              <td align="center" valign="middle">&gt; 50%</td>
              <td align="center" valign="middle">86%</td>
              <td align="center" valign="middle">91%</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">149 DP</td>
              <td align="center" valign="middle">&lt; 2</td>
              <td align="center" valign="middle"/>
              <td align="center" valign="middle">&gt; 50%</td>
              <td align="center" valign="middle">92%</td>
              <td align="center" valign="middle">92%</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">142 CX</td>
              <td align="center" valign="middle">&lt; 2</td>
              <td align="center" valign="middle"/>
              <td align="center" valign="middle">&gt; 50%</td>
              <td align="center" valign="middle">91%</td>
              <td align="center" valign="middle">92%</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN11">
            <p>RFC: Reserva de fluxo coronariano; ADA: Art&#233;ria coron&#225;ria descendente anterior; DP: Descendente posterior; CX: Circunflexa.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>Na estenose intermedi&#225;ria (50% - 70%) da ADA, pode-se optar pela interven&#231;&#227;o hemodin&#226;mica quando a RFC &#233; reduzida, ou pelo tratamento cl&#237;nico se a RFC for normal, visto que no estudo de D&#8217;Andrea et al. n&#227;o houve diferen&#231;a na ocorr&#234;ncia de &#243;bito, infarto, angina inst&#225;vel ou revasculariza&#231;&#227;o mioc&#225;rdica nos dois grupos.<sup><xref ref-type="bibr" rid="B195">195</xref></sup></p>
      <p>A RFC anormal evidencia sensibilidade e especificidade elevadas para diagn&#243;stico de restenose nas tr&#234;s principais coron&#225;rias (<xref ref-type="table" rid="t21">Tabela 18.1</xref>). Um estudo mostrou exequibilidade de registro elevada na ADA (95%), DP (85%) e CX (81%) e utilizou ARUS ou contraste de microbolhas em 22% dos casos.<sup><xref ref-type="bibr" rid="B194">194</xref></sup></p>
      <p>A dobutamina &#233; o estressor mais utilizado para a ecocardiografia de estresse farmacol&#243;gico e apresenta tamb&#233;m a&#231;&#227;o vasodilatadora.<sup><xref ref-type="bibr" rid="B196">196</xref></sup> O primeiro estudo a avaliar a RFC na ADA com dobutamina mostrou exequibilidade de 90%. Os casos com isquemia pelo crit&#233;rio de anormalidade contr&#225;til apresentaram RFC = 1,51 &#177; 0,51, enquanto os sem isquemia tiveram RFC = 2,76 &#177; 0,65.<sup><xref ref-type="bibr" rid="B186">186</xref></sup></p>
      <p>Durante a ecocardiografia de estresse com dobutamina, uma RFC normal e precoce pode ser obtida antes de atingir a FC alvo do exame.<sup><xref ref-type="bibr" rid="B197">197</xref></sup> Os casos com RFC normal e precoce apresentaram melhor desfecho combinado do que as RFCs normais registradas ap&#243;s a FC subm&#225;xima e as RFC anormais. Ap&#243;s obter uma RFC precoce e normal, o registro desta pode ser interrompido e apenas a ecocardiografia de estresse continuada.<sup><xref ref-type="bibr" rid="B179">179</xref></sup></p>
      <p>Em pacientes diab&#233;ticos submetidos a ecocardiografia de estresse com dipiridamol ou dobutamina, verificou-se, nos casos sem isquemia, que a RFC anormal na ADA foi preditor independente de mortalidade e similar por ambas as t&#233;cnicas.<sup><xref ref-type="bibr" rid="B199">199</xref></sup> A observa&#231;&#227;o foi corroborada em um estudo com dipiridamol que avaliou a RFC em ADA e DP, constatando que a RFC anormal &#233; preditor de pior progn&#243;stico (&#243;bito e infarto do mioc&#225;rdio) em pacientes sem isquemia.<sup><xref ref-type="bibr" rid="B189">189</xref></sup></p>
    </sec>
    <sec>
      <title>19. Ecocardiografia de Estresse e Reserva de Fluxo Coronariano em Enxertos</title>
      <p>A an&#225;lise anat&#244;mica da les&#227;o de vasos epic&#225;rdicos por coronariografia pode n&#227;o ser suficiente para avaliar a repercuss&#227;o da les&#227;o coronariana, principalmente em obstru&#231;&#245;es intermedi&#225;rias, de 50 a 70%, e em pacientes multiarteriais,<sup><xref ref-type="bibr" rid="B200">200</xref></sup> em parte devido &#224;s modifica&#231;&#245;es que a estenose provoca na regula&#231;&#227;o da circula&#231;&#227;o. Uma estenose &gt; 50% da luz aumenta a resist&#234;ncia coron&#225;ria e diminui a press&#227;o ap&#243;s a obstru&#231;&#227;o, com diminui&#231;&#227;o da RFC.<sup><xref ref-type="bibr" rid="B201">201</xref></sup> Por esse motivo, a avalia&#231;&#227;o fisiol&#243;gica da circula&#231;&#227;o coronariana, como determinante da revasculariza&#231;&#227;o mioc&#225;rdica, tem melhorado os resultados dos procedimentos, tanto cir&#250;rgicos como percut&#226;neos, assim como o progn&#243;stico p&#243;s procedimento. Nesse sentido, entre outros m&#233;todos diagn&#243;sticos, al&#233;m da coronariografia, destacam-se a ecocardiografia de estresse e a an&#225;lise da RFC com Doppler transtor&#225;cico.</p>
      <sec>
        <title>19.1. Ecocardiografia de Estresse ap&#243;s Revasculariza&#231;&#227;o Mioc&#225;rdica</title>
        <p>Assim como o WMSI &gt; 1,7 na ecocardiografia de estresse realizada antes da revasculariza&#231;&#227;o &#233; preditor de aumento das complica&#231;&#245;es p&#243;s-operat&#243;rias,<sup><xref ref-type="bibr" rid="B202">202</xref></sup> um estudo anormal ap&#243;s a revasculariza&#231;&#227;o aumenta mais de duas vezes o risco de eventos cardiovasculares adversos,<sup><xref ref-type="bibr" rid="B203">203</xref></sup> mesmo em pacientes assintom&#225;ticos. Apesar da ecocardiografia de estresse com vasodilatador ser a melhor op&#231;&#227;o para esses casos, o estresse com dobutamina em baixa dose, embora influenciado por diversos fatores, tem demonstrado boa sensibilidade (86,4%) para detectar a recupera&#231;&#227;o da reserva contr&#225;til ap&#243;s a revasculariza&#231;&#227;o, principalmente em segmentos previamente hipocin&#233;ticos.<sup><xref ref-type="bibr" rid="B204">204</xref></sup></p>
      </sec>
      <sec>
        <title>19.2. Reserva de Fluxo Coronariano ap&#243;s Revasculariza&#231;&#227;o Mioc&#225;rdica</title>
        <p>A RFC fracionada realizada durante o estudo hemodin&#226;mico, seja pelo gradiente press&#243;rico ou pela velocidade do fluxo atrav&#233;s da obstru&#231;&#227;o, &#233; uma ferramenta importante para a an&#225;lise funcional da doen&#231;a coronariana obstrutiva, sendo recomendado como Classe IA.<sup><xref ref-type="bibr" rid="B205">205</xref></sup> Em pacientes revascularizados, como substituto dos m&#233;todos invasivos, &#233; poss&#237;vel usar a medi&#231;&#227;o do fluxo coronariano com Doppler transtor&#225;cico e a RFC com vasodilatadores.<sup><xref ref-type="bibr" rid="B206">206</xref></sup> Em enxertos realizados com art&#233;ria tor&#225;cica interna (mam&#225;ria interna), a ocorr&#234;ncia de fluxo bif&#225;sico com predom&#237;nio diast&#243;lico na art&#233;ria mam&#225;ria indica pat&#234;ncia do enxerto (<xref ref-type="fig" rid="f21">Figura 19.1</xref>). O aumento da velocidade do fluxo coronariano distal ao local do enxerto ap&#243;s a infus&#227;o de vasodilatadores (usa-se dipiridamol 0,84 mg/kg em 6 minutos, embora a obten&#231;&#227;o da RFC j&#225; seja considerada satisfat&#243;ria em 4 minutos; ou adenosina 140 mcg/kg/min durante 2 minutos) permite determinar a RFC, sendo considerada boa resposta uma rela&#231;&#227;o entre o fluxo basal e com hiperemia &gt; 2<sup><xref ref-type="bibr" rid="B207">207</xref></sup> (<xref ref-type="fig" rid="f22">Figura 19.2</xref>).</p>
        <fig id="f21">
          <label>Figura 19.1</label>
          <caption>
            <title>A: detec&#231;&#227;o do fluxo da art&#233;ria tor&#225;cica interna com posicionamento do volume-amostra do Doppler puls&#225;til. B: registro do fluxo do enxerto mam&#225;rio-coron&#225;rio observando-se fluxo bif&#225;sico com predom&#237;nio diast&#243;lico, indicando que o enxerto se encontra p&#233;rvio.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <fig id="f22">
          <label>Figura 19.2</label>
          <caption>
            <title>Fluxo coronariano em enxerto com art&#233;ria tor&#225;cica interna. A: fluxo coronariano basal obtido no ramo descendente anterior ap&#243;s a anastomose. B: fluxo obtido 6 minutos ap&#243;s a infus&#227;o de dipiridamol mostrando uma reserva de fluxo coronariano (RFC) de 2,35. A rampa de desacelera&#231;&#227;o do tra&#231;ado diast&#243;lico correlaciona-se com a resist&#234;ncia oferecida pelo leito vascular &#224; passagem do fluxo durante a di&#225;stole. A vasodilata&#231;&#227;o diminui a resist&#234;ncia vascular com desacelera&#231;&#227;o mais r&#225;pida do fluxo.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>Em enxertos venosos, o fluxo no enxerto &#233; predominantemente sist&#243;lico, sofrendo esvaziamento para a art&#233;ria coron&#225;ria durante a di&#225;stole (<xref ref-type="fig" rid="f23">Figura 19.3</xref>). A an&#225;lise e interpreta&#231;&#227;o da RFC &#233; semelhante &#224; do enxerto arterial.</p>
        <fig id="f23">
          <label>Figura 19.3</label>
          <caption>
            <title>Fluxo coronariano em enxerto venoso para o ramo descendente anterior. A: fluxo no enxerto venoso, com predom&#237;nio sist&#243;lico. B: fluxo na art&#233;ria distal ao enxerto com fluxo bif&#225;sico com predom&#237;nio diast&#243;lico.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>Algumas condi&#231;&#245;es podem diminuir a RFC nos enxertos arteriais sem necessariamente haver estenose, como: ateromatose da art&#233;ria subcl&#225;via esquerda ou do enxerto arterial que pode diminuir o fluxo para a art&#233;ria enxertada; ateromatose difusa do leito distal da art&#233;ria irrigada; infarto pr&#233;vio com aumento da resist&#234;ncia microvascular; altera&#231;&#245;es da microcircula&#231;&#227;o coronariana; e momento da realiza&#231;&#227;o do exame, devido ao remodelamento gradativo dos enxertos arteriais, com aumento progressivo da RFC. Para os enxertos venosos, temos o espasmo do enxerto, condi&#231;&#227;o rara, por&#233;m, grave; aterosclerose do enxerto; e hipoplasia fibro-intimal com fibrose.</p>
      </sec>
    </sec>
    <sec>
      <title>20. Ecocardiografia de Estresse na An&#225;lise de Viabilidade Mioc&#225;rdica</title>
      <p>A abordagem cl&#237;nica de &#225;reas mioc&#225;rdicas acin&#233;ticas com viabilidade por estudos de imagem (mioc&#225;rdio hibernante) &#233; controversa, principalmente ap&#243;s dois grandes estudos, o STICH (<italic>Surgical Treatment for Ischaemic Heart Failure</italic>) e o HEART (<italic>Heart Failure Revascularization</italic>) que, apesar de mostrarem melhora da FEVE, n&#227;o impactaram positivamente no progn&#243;stico desses pacientes no longo prazo.<sup><xref ref-type="bibr" rid="B208">208</xref>,<xref ref-type="bibr" rid="B209">209</xref></sup> O mioc&#225;rdio hibernante se refere a &#225;reas disfuncionantes por hipoperfus&#227;o cr&#244;nica, por doen&#231;a coronariana obstrutiva, com poss&#237;vel reversibilidade ap&#243;s revasculariza&#231;&#227;o.<sup><xref ref-type="bibr" rid="B210">210</xref></sup> Isso intriga a cardiologia e ainda &#233; um tema controverso. Dentre os m&#233;todos de imagem, a tomografia por emiss&#227;o de p&#243;sitrons (PET &#8211; <italic>positron emission tomography</italic>) tem a maior sensibilidade e valor preditivo negativo, enquanto a ecocardiografia de estresse farmacol&#243;gico com dobutamina &#233; a mais espec&#237;fica e com maior valor preditivo positivo por segmento analisado.<sup><xref ref-type="bibr" rid="B211">211</xref></sup> Atualmente, h&#225; uma revis&#227;o conceitual em rela&#231;&#227;o ao modo e poss&#237;veis benef&#237;cios da revasculariza&#231;&#227;o guiada pela an&#225;lise pr&#233;via da viabilidade mioc&#225;rdica. A concep&#231;&#227;o anterior valorizava a presen&#231;a de viabilidade, independente da anatomia coronariana para revasculariza&#231;&#227;o. Essa estrat&#233;gia demonstrava uma melhora da FE, da qualidade de vida, dos sintomas e da insufici&#234;ncia card&#237;aca isqu&#234;mica, contudo, a FE em si n&#227;o influenciava necessariamente a melhora da sobrevida. A abordagem atual visa uma avalia&#231;&#227;o mais funcional e espec&#237;fica ao mioc&#225;rdio, melhorando o planejamento terap&#234;utico com uma revasculariza&#231;&#227;o mais racional e fisiol&#243;gica. Com isso, h&#225; uma preocupa&#231;&#227;o maior em preservar os segmentos com isquemia e viabilidade que tenham uma anatomia favor&#225;vel para revasculariza&#231;&#227;o cir&#250;rgica, reduzindo, dessa forma, a taxa de infartos e arritmias fatais.<sup><xref ref-type="bibr" rid="B210">210</xref></sup> Curiosamente, a revasculariza&#231;&#227;o percut&#226;nea guiada pela pesquisa de viabilidade n&#227;o demonstrou benef&#237;cios.<sup><xref ref-type="bibr" rid="B212">212</xref>,<xref ref-type="bibr" rid="B213">213</xref></sup></p>
      <sec>
        <title>20.1. Protocolo de Estresse para An&#225;lise de Viabilidade Mioc&#225;rdica</title>
        <p>Antes do estudo de viabilidade mioc&#225;rdica, a ecocardiografia transtor&#225;cica dirigida &#233; realizada de forma habitual. Essa fase informa o examinador sobre os par&#226;metros basais a serem analisados sob condi&#231;&#245;es din&#226;micas, assim como sobre a qualidade da janela ecocardiogr&#225;fica, antecipando a necessidade de utiliza&#231;&#227;o de agentes de realce ultrassonogr&#225;fico. A avalia&#231;&#227;o de viabilidade &#233; realizada pelo protocolo de ecocardiografia de estresse farmacol&#243;gico com dobutamina em baixa dose (iniciando com 2,5 ou 5 mcg/kg/min com incrementos para 7,5 e 10 mcg/kg/min, a cada 3 a 5 minutos, chegando at&#233; 20 mcg/kg/min). O protocolo tamb&#233;m pode ser realizado em pacientes em uso de betabloqueador. A despeito da avalia&#231;&#227;o de viabilidade com baixas doses de dobutamina, &#233; interessante progredir com doses maiores (at&#233; 40 mcg/kg/min com ou sem atropina) para avaliar, al&#233;m da viabilidade, a presen&#231;a de isquemia mioc&#225;rdica induzida por estresse que muito contribui para a mudan&#231;a de conduta. Isso vale naqueles pacientes que permitem a evolu&#231;&#227;o do protocolo, preferencialmente nos que n&#227;o apresentam FE muito reduzida por hipocinesia acentuada de v&#225;rios segmentos, al&#233;m de &#225;reas acin&#233;ticas. Nesses casos, o risco do protocolo em alta dose aumenta e a sensibilidade do m&#233;todo &#233; reduzida para diagn&#243;stico de isquemia pela altera&#231;&#227;o acentuada e "balanceada" de todas as paredes do VE.</p>
        <p>A presen&#231;a de viabilidade &#233; reconhecida pela ecocardiografia transtor&#225;cica com dobutamina quando os segmentos acin&#233;ticos em repouso apresentam aumento da espessura (&#8805;0,5 cm) e da contratilidade (reserva contr&#225;til) ao estresse. Em pacientes que apresentam resposta bif&#225;sica com o avan&#231;o do protocolo (melhora em baixa dose e piora em dose mais elevada de dobutamina, 20 mcg/kg/min ou mais), o fen&#244;meno sugere maior n&#250;mero de segmentos vi&#225;veis e com isquemia, chamado tamb&#233;m de isqu&#234;mico-vi&#225;vel, e &#233; a melhor resposta que denota recupera&#231;&#227;o funcional p&#243;s-revasculariza&#231;&#227;o. Isso vale especialmente quando essa viabilidade, chamada resposta bif&#225;sica, ocorre em quatro ou mais segmentos acin&#233;ticos em repouso, em paciente com disfun&#231;&#227;o sist&#243;lica do VE. Geralmente, esse grupo de pacientes apresenta melhores respostas &#224; revasculariza&#231;&#227;o mioc&#225;rdica, inclusive com melhora da FE, ao contr&#225;rio daqueles que s&#243; apresentam melhora da contratilidade com baixas e altas doses de dobutamina (melhora sustentada); assim como aqueles que apresentam piora da contratilidade nas regi&#245;es hipocin&#233;ticas em baixas doses de estresse farmacol&#243;gico<sup><xref ref-type="bibr" rid="B214">214</xref>,<xref ref-type="bibr" rid="B215">215</xref></sup> (<xref ref-type="fig" rid="f24">Figura 20.1</xref>).</p>
        <fig id="f24">
          <label>Figura 20.1</label>
          <caption>
            <title>Algoritmo sint&#233;tico de conduta na abordagem do mioc&#225;rdio hibernante. FEVE: fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo; RMC: revasculariza&#231;&#227;o mioc&#225;rdica; TCO: terapia cl&#237;nica otimizada.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
      </sec>
      <sec>
        <title>20.2. An&#225;lise da Viabilidade Mioc&#225;rdica pelo <italic>Strain</italic> Longitudinal</title>
        <p>A avalia&#231;&#227;o da viabilidade mioc&#225;rdica por meio da an&#225;lise da deforma&#231;&#227;o (<italic>strain</italic>) global longitudinal do VE por ecocardiografia bidimensional &#233; uma &#225;rea de pesquisa ativa e relevante. A medi&#231;&#227;o do <italic>strain</italic> e do <italic>strain rate</italic> (SR) por ecocardiografia &#233; uma t&#233;cnica desafiadora, mas promissora para avaliar a fun&#231;&#227;o ventricular em repouso, viabilidade mioc&#225;rdica e isquemia durante o teste de estresse. Em baixas doses de dobutamina, ocorre aumento do <italic>strain</italic> e do SR nos segmentos vi&#225;veis e redu&#231;&#227;o do encurtamento p&#243;s-sist&#243;lico. Por outro lado, nos segmentos com acometimento transmural do infarto, observa-se apenas um aumento discreto e transit&#243;rio do SR, sem aumento do <italic>strain</italic> global longitudinal e aumento do encurtamento p&#243;s-sist&#243;lico. As principais altera&#231;&#245;es da an&#225;lise de deforma&#231;&#227;o est&#227;o resumidas de forma sint&#233;tica na <xref ref-type="fig" rid="f25">Figura 20.2</xref>.<sup><xref ref-type="bibr" rid="B215">215</xref>-<xref ref-type="bibr" rid="B217">217</xref></sup> Apesar dos resultados interessantes em agregar informa&#231;&#245;es ao m&#233;todo, ainda faltam estudos que comprovem o seu benef&#237;cio cl&#237;nico, guiando a terap&#234;utica a partir de dados incrementais da deforma&#231;&#227;o mioc&#225;rdica. Por isso, o <italic>strain</italic> global longitudinal n&#227;o &#233; atualmente uma t&#233;cnica substitutiva.</p>
        <fig id="f25">
          <label>Figura 20.2</label>
          <caption>
            <title>Principais altera&#231;&#245;es da an&#225;lise de deforma&#231;&#227;o mioc&#225;rdica pelo strain longitudinal global na viabilidade mioc&#225;rdica.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>Independentemente da decis&#227;o cl&#237;nica de revasculariza&#231;&#227;o cir&#250;rgica ou tratamento cl&#237;nico, a presen&#231;a e a extens&#227;o de segmentos vi&#225;veis demonstram um substrato para resposta terap&#234;utica, como terapia de ressincroniza&#231;&#227;o card&#237;aca e terapia farmacol&#243;gica, e n&#227;o apenas a revasculariza&#231;&#227;o mioc&#225;rdica.<sup><xref ref-type="bibr" rid="B218">218</xref></sup></p>
        <p>Assim, os pacientes que apresentam segmentos vi&#225;veis t&#234;m melhor resposta terap&#234;utica e melhor progn&#243;stico quando submetidos a interven&#231;&#245;es cl&#237;nicas ou cir&#250;rgicas.</p>
      </sec>
    </sec>
    <sec>
      <title>21. Ecocardiografia de Estresse com Agente de Realce Ultrassonogr&#225;fico na An&#225;lise da Borda Endoc&#225;rdica</title>
      <p>Em todas as modalidades de estresse, o ARUS, nomenclatura mais recente para o contraste de microbolhas ou de ultrassom, pode e deve ser utilizado.</p>
      <p>No caso da esteira, as imagens iniciais s&#227;o obtidas em repouso e as imagens no p&#243;s-esfor&#231;o imediato idealmente at&#233; 90 segundos ap&#243;s o t&#233;rmino do exerc&#237;cio f&#237;sico, quando o paciente deita e as imagens s&#227;o adquiridas. No caso da ciclomaca ou bicicleta ergom&#233;trica, assim como no estresse farmacol&#243;gico, as imagens s&#227;o obtidas continuamente durante os diversos est&#225;gios do esfor&#231;o. Com isso, a administra&#231;&#227;o de ARUS difere de acordo com a modalidade de estresse adotada.</p>
      <p>Sabemos que alguns pacientes n&#227;o possuem janela ecocardiogr&#225;fica satisfat&#243;ria, o que pode comprometer a qualidade e interpreta&#231;&#227;o do exame. Nesses casos, o uso desses agentes, que permitem a visualiza&#231;&#227;o perfeita dos bordos das paredes do cora&#231;&#227;o, se tornam imprescind&#237;veis. A visualiza&#231;&#227;o segmentar detalhada &#233; fundamental para a detec&#231;&#227;o de DAC. A visualiza&#231;&#227;o de todos os segmentos em repouso e durante o estresse &#233; importante para determinar a extens&#227;o da isquemia induzida ou a presen&#231;a de infarto pr&#233;vio.<sup><xref ref-type="bibr" rid="B219">219</xref>,<xref ref-type="bibr" rid="B220">220</xref></sup></p>
      <p>Atualmente, a tend&#234;ncia &#233; n&#227;o chamar esses agentes de "contraste", para que n&#227;o sejam associados &#224;queles usados em radiologia ou na resson&#226;ncia magn&#233;tica, com potencial t&#243;xico e al&#233;rgico infinitamente maiores do que o "contraste" para ultrassom.<sup><xref ref-type="bibr" rid="B221">221</xref></sup> Por isso, esta diretriz adota a sigla "ARUS".</p>
      <p>A ecocardiografia de estresse com ARUS apresenta maior sensibilidade, especificidade e acur&#225;cia diagn&#243;stica.<sup><xref ref-type="bibr" rid="B222">222</xref>,<xref ref-type="bibr" rid="B223">223</xref></sup></p>
      <p>Al&#233;m disso, o exame com ARUS pode ter melhor rela&#231;&#227;o custo-benef&#237;cio quando utilizado com indica&#231;&#227;o, especialmente quando dois ou mais segmentos n&#227;o s&#227;o bem visualizados ao corte apical,<sup><xref ref-type="bibr" rid="B223">223</xref></sup> e assim evitar exames mais onerosos e com potencial de toxicidade renal ou uso de radia&#231;&#227;o.</p>
      <sec>
        <title>21.1. Agente de Realce Ultrassonogr&#225;fico</title>
        <p>Atualmente, o &#250;nico ARUS registrado no Brasil &#233; o Sonovue (Bracco), cuja composi&#231;&#227;o &#233; de microbolhas a partir de g&#225;s de enxofre. Na sua grande maioria, essas bolhas s&#227;o menores do que 5 m&#237;crons ou micr&#244;metros e atravessam os capilares pulmonares, chegando rapidamente (cerca de 2 segundos) ao lado esquerdo do cora&#231;&#227;o e real&#231;ando os bordos das paredes do VE. Esses agentes melhoram a imagem e a confian&#231;a na interpreta&#231;&#227;o do teste.<sup><xref ref-type="bibr" rid="B219">219</xref>-<xref ref-type="bibr" rid="B222">222</xref></sup></p>
        <p>A literatura que corrobora a seguran&#231;a dos ARUS &#233; enorme, e rea&#231;&#245;es anafilactoides, apesar de muito raras, demandam a necessidade de ter medica&#231;&#245;es e materiais de ressuscita&#231;&#227;o cardiopulmonar prontamente acess&#237;veis.<sup><xref ref-type="bibr" rid="B223">223</xref></sup></p>
        <sec>
          <title>21.1.1. Forma de Administra&#231;&#227;o</title>
          <p>A maioria dos equipamentos modernos apresenta <italic>presets</italic> espec&#237;ficos para o uso dos ARUS na an&#225;lise da borda endoc&#225;rdica e opacifica&#231;&#227;o da cavidade ventricular (e n&#227;o para an&#225;lise da perfus&#227;o). E embora o ARUS possa ser administrado na forma de bolus ou de infus&#227;o cont&#237;nua, avalia-se que a forma em bolus &#233; mais pr&#225;tica e de excelente resultado. A administra&#231;&#227;o do ARUS deve ser o suficiente para opacificar o cora&#231;&#227;o de forma homog&#234;nea, sem causar redemoinho no &#225;pice ou atenua&#231;&#227;o na base do cora&#231;&#227;o. Deve-se trabalhar com os protocolos de f&#225;brica do aparelho que apresentam o IM baixo (&lt; 0,3), com harm&#244;nica ou com sequ&#234;ncia de pulso n&#227;o linear.<sup><xref ref-type="bibr" rid="B224">224</xref>,<xref ref-type="bibr" rid="B225">225</xref></sup> Em equipamentos mais modernos, um IM muito baixo (&lt; 0,2) evita a destrui&#231;&#227;o das microbolhas, real&#231;a o sinal das microbolhas e reduz os artefatos, permitindo uma excelente delimita&#231;&#227;o dos bordos endoc&#225;rdicos.</p>
          <p>Alguns servi&#231;os usam o ARUS em todos os exames de ecocardiografia de estresse como maneira de melhorar a acur&#225;cia do teste. Contudo, a rela&#231;&#227;o custo-efetividade &#233; question&#225;vel nesses casos, uma vez que a necessidade real de muitos centros parece girar em torno de 20% dos casos.</p>
          <p>Durante a ecocardiografia de estresse farmacol&#243;gico associada &#224; ARUS, utilizam-se presets de estresse com contraste para o delineamento da borda endoc&#225;rdica. Quando se deseja avaliar a perfus&#227;o (que depende de um software espec&#237;fico e mais sofisticado, que n&#227;o &#233; o mesmo para a an&#225;lise da borda endoc&#225;rdica), em vez do <italic>preset</italic> de an&#225;lise das bordas endoc&#225;rdicas, utiliza-se o <italic>preset</italic> adequado para perfus&#227;o mioc&#225;rdica (com softwares do tipo <italic>pulse inversion</italic>, <italic>power modulation</italic> ou <italic>cadence</italic>). Vale considerar que a an&#225;lise da perfus&#227;o mioc&#225;rdica requer conhecimento especializado e uma curva de aprendizado maior que a an&#225;lise da borda endoc&#225;rdica.</p>
          <p>Para aplica&#231;&#227;o do ARUS, utiliza-se um equipo com duas vias ou, preferivelmente, uma torneirinha no acesso perif&#233;rico obtido com cateter tipo abocath de bom calibre, e deixa-se uma das vias em linha reta para a administra&#231;&#227;o do ARUS. O ARUS &#233; administrado antes do in&#237;cio do teste (imagens basais) e antes/durante cada etapa do protocolo de estresse para a obten&#231;&#227;o de imagens compar&#225;veis. Na primeira inje&#231;&#227;o, utiliza-se um <italic>bolus</italic> de aproximadamente 0,5 mL, e pode ou n&#227;o ser administrado um <italic>flush</italic> de soro fisiol&#243;gico (solu&#231;&#227;o salina) lentamente ap&#243;s (a administra&#231;&#227;o r&#225;pida do ARUS e/ou do soro ocasiona hipersinal com sombra nas regi&#245;es m&#233;dio-distais do cora&#231;&#227;o). Durante as etapas com infus&#227;o da dobutamina, n&#227;o se utiliza mais o <italic>flush</italic> de solu&#231;&#227;o salina ap&#243;s.</p>
          <p>Durante a ecocardiografia de esfor&#231;o em esteira, d&#225;-se prefer&#234;ncia &#224; coloca&#231;&#227;o de um acesso no membro superior esquerdo (prefer&#234;ncia no antebra&#231;o) do paciente e a administra&#231;&#227;o &#233; realizada cerca de 15-20 segundos antes do pico de esfor&#231;o e antes do paciente ser conduzido &#224; maca de exame para aquisi&#231;&#227;o das imagens ecocardiogr&#225;ficas no p&#243;s-esfor&#231;o imediato. Tamb&#233;m n&#227;o h&#225; necessidade do <italic>flush</italic> ap&#243;s a administra&#231;&#227;o do ARUS nesse caso. As imagens basais s&#227;o obtidas assim que o paciente se deita na maca de exame.</p>
          <p>Por meio do software de estresse com <italic>quad-screen</italic>, o aparelho de ecocardiografia coloca as imagens card&#237;acas lado a lado, facilitando a interpreta&#231;&#227;o do teste. Idealmente, o ARUS deve ser usado em todas as etapas do estresse (<xref ref-type="fig" rid="f26">Figura 21.1</xref>).</p>
          <fig id="f26">
            <label>Figura 21.1</label>
            <caption>
              <title>As imagens lado a lado em quad-screen facilitam a interpreta&#231;&#227;o do teste nas diferentes fases do exame.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <p>Vale refor&#231;ar que quando o ARUS &#233; utilizado junto &#224; ecocardiografia de estresse, o ideal &#233; iniciar a obten&#231;&#227;o das imagens pela janela apical. Esta pode ser a &#250;nica usada para a obten&#231;&#227;o de todas as paredes do VE, pois o &#225;pice do VE deve estar bem opacificado. Ele &#233; o que mais sofre com a destrui&#231;&#227;o das bolhas pela insona&#231;&#227;o e, por isso, deve ser avaliado primariamente.</p>
        </sec>
      </sec>
    </sec>
    <sec>
      <title>22. Ecocardiografia de Estresse com Agente de Realce Ultrassonogr&#225;fico na An&#225;lise da Perfus&#227;o Mioc&#225;rdica</title>
      <p>O volume de sangue na circula&#231;&#227;o coronariana se encontra majoritariamente (cerca de 90 %) no interior dos capilares. Da mesma forma que os ARUS, quando interagem com o ultrassom, opacificam a cavidade ventricular esquerda, as microbolhas dentro dos capilares conferem um aspecto cintilante intramioc&#225;rdico. Assim, a intensidade desse brilho est&#225; correlacionada com o volume de sangue dentro da microvasculariza&#231;&#227;o.</p>
      <p>Ap&#243;s a administra&#231;&#227;o do ARUS, a perfus&#227;o mioc&#225;rdica (PM) &#233; avaliada nas tr&#234;s incid&#234;ncias ecocardiogr&#225;ficas apicais do VE. Isso pode ser realizado tanto em infus&#227;o cont&#237;nua do agente ou, mais rotineiramente, em bolus.</p>
      <p>Em caso de an&#225;lise concomitante de contra&#231;&#227;o e perfus&#227;o mioc&#225;rdica, utiliza-se a t&#233;cnica de destrui&#231;&#227;o/reperfus&#227;o (repreenchimento) das microbolhas, usando IM muito baixo, especialmente quando a an&#225;lise &#233; realizada com o software espec&#237;fico para an&#225;lise da perfus&#227;o em tempo real (IM &lt; 0,2), atualmente considerada ideal para essa an&#225;lise (e n&#227;o o software padr&#227;o para an&#225;lise da borda endoc&#225;rdica). Essa t&#233;cnica &#233; importante para definir a velocidade de repreenchimento da parede mioc&#225;rdica e a presen&#231;a ou n&#227;o de isquemia.</p>
      <p>Ap&#243;s a administra&#231;&#227;o do ARUS, assim que uma opacifica&#231;&#227;o adequada do VE &#233; atingida, &#233; disparado um pulso de alta energia (flash; alto IM: 0,8 &#8211; 1,2)<sup><xref ref-type="bibr" rid="B226">226</xref></sup> que destr&#243;i as microbolhas no volume sangu&#237;neo capilar intramioc&#225;rdico, preservando relativamente as microbolhas intracavit&#225;rias. Havendo obstru&#231;&#227;o limitante do fluxo coron&#225;rio nas art&#233;rias epic&#225;rdicas e/ou na microvasculariza&#231;&#227;o, o resultado final observado &#233; um brilho mioc&#225;rdico mais atenuado ou at&#233; ausente (zona enegrecida) do segmento afetado (<xref ref-type="fig" rid="f27">Figura 22.1</xref>).</p>
      <fig id="f27">
        <label>Figura 22.1</label>
        <caption>
          <title>Mulher de 60 anos submetida a ecocardiografia com agente de realce ultrassonogr&#225;fico sob estresse farmacol&#243;gico pela dobutamina. Apresentou desconforto tor&#225;cico e infradesnivelamento do segmento ST em deriva&#231;&#245;es precordiais no tra&#231;ado eletrocardiogr&#225;fico. Observa-se &#225;rea com d&#233;ficit de perfus&#227;o mioc&#225;rdica no &#225;pice do ventr&#237;culo esquerdo associada a hipocinesia local (setas). Teste positivo para presen&#231;a de isquemia mioc&#225;rdica apical.</title>
        </caption>
        <graphic xlink:href=""/>
      </fig>
      <p>Essa an&#225;lise &#233; realizada rotineiramente durante o exame. Contudo, a an&#225;lise off-line se mostrou superior pelo fato de possibilitar uma an&#225;lise objetiva dos dois componentes da PM: o volume de sangue capilar (componente &#945;) e a velocidade sangu&#237;nea capilar (componente &#946;). A PM seria o fluxo de sangue da microvasculariza&#231;&#227;o determinado pelo produto desses dois componentes (&#945; &#215; &#946;), conforme demonstrado na <xref ref-type="fig" rid="f28">Figura 22.2</xref>. A redu&#231;&#227;o do componente &#945; pode estar relacionada a &#225;reas infartadas ou restri&#231;&#227;o significativa do fluxo microvascular, enquanto a diminui&#231;&#227;o do componente &#946; est&#225; correlacionada com a redu&#231;&#227;o do fluxo capilar associada a DAC obstrutiva ou MINOCA. No MINOCA, h&#225; um retardo com d&#233;ficit da PM, mas com espessamento mioc&#225;rdico preservado, dada a aus&#234;ncia de comprometimento subendoc&#225;rdico.<sup><xref ref-type="bibr" rid="B227">227</xref></sup> Esse diagn&#243;stico &#233; realizado pela an&#225;lise da perfus&#227;o-contra&#231;&#227;o, na qual se avalia em conjunto a PM e motilidade segmentar mioc&#225;rdica, como tamb&#233;m pela demonstra&#231;&#227;o de uma reserva de fluxo da microvasculariza&#231;&#227;o &lt; 2, preferencialmente realizada na ecocardiografia de estresse com vasodilatador.<sup><xref ref-type="bibr" rid="B228">228</xref>,<xref ref-type="bibr" rid="B229">229</xref></sup> O componente &#946; &#233; superior ao &#945; em termos de sensibilidade para detec&#231;&#227;o de DAC.<sup><xref ref-type="bibr" rid="B230">230</xref></sup> Em geral, uma PM normal se baseia no repreenchimento mioc&#225;rdico (reestabelecimento total do sinal medido em decib&#233;is) em menos de 5 segundos no repouso (para FC de 60 bpm) ou at&#233; 2 segundos durante o estresse (para FC de 120 bpm). Essa an&#225;lise deve ser realizada no final da s&#237;stole.<sup><xref ref-type="bibr" rid="B230">230</xref></sup></p>
      <fig id="f28">
        <label>Figura 22.2</label>
        <caption>
          <title>Exemplo de an&#225;lise off-line da perfus&#227;o mioc&#225;rdica. Janela apical de duas c&#226;maras do VE. Presen&#231;a de &#225;rea extensa de d&#233;ficit de perfus&#227;o mioc&#225;rdica na parede anterior (em vermelho). A, an&#225;lise do volume de sangue capilar (componente &#945;). B, an&#225;lise da velocidade sangu&#237;nea capilar (componente &#946;). C, an&#225;lise do fluxo de sangue da microvasculariza&#231;&#227;o (&#945; &#215; &#946;).</title>
        </caption>
        <graphic xlink:href=""/>
      </fig>
      <p>A PM &#233; um grande aux&#237;lio &#224; avalia&#231;&#227;o convencional subjetiva da motilidade e espessamento segmentar mioc&#225;rdico, base da avalia&#231;&#227;o da ecocardiografia sob estresse, aumentando a sensibilidade do m&#233;todo para detectar a DAC, conforme demonstrado por diversos estudos.<sup><xref ref-type="bibr" rid="B231">231</xref>-<xref ref-type="bibr" rid="B233">233</xref></sup> O m&#233;todo tamb&#233;m se mostrou superior em sensibilidade para detectar DAC obstrutiva em rela&#231;&#227;o &#224; cintilografia com SPECT.<sup><xref ref-type="bibr" rid="B234">234</xref></sup> Um dos motivos &#233; justamente o fato de a cintilografia detectar o volume sangu&#237;neo capilar,<sup><xref ref-type="bibr" rid="B235">235</xref></sup> enquanto a PM pelo ecocardiograma possibilita avaliar, tamb&#233;m, a velocidade do fluxo sangu&#237;neo capilar, que sabe-se ser um marcador mais sens&#237;vel para a detec&#231;&#227;o de DAC.<sup><xref ref-type="bibr" rid="B230">230</xref></sup></p>
      <p>Estudos de acur&#225;cia para detec&#231;&#227;o de DAC demonstram que a ecocardiografia de estresse associada &#224; an&#225;lise de PM tem sensibilidade de 83% e especificidade 79% quando se utiliza um vasodilatador;<sup><xref ref-type="bibr" rid="B236">236</xref>,<xref ref-type="bibr" rid="B237">237</xref></sup> quando se utiliza dobutamina ou estresse f&#237;sico, tem sensibilidade e especificidade de 88% e 77%, respectivamente.<sup><xref ref-type="bibr" rid="B237">237</xref></sup></p>
      <p>Al&#233;m de aumentar a detec&#231;&#227;o de DAC, a ecocardiografia com an&#225;lise da PM &#233; um bom indicador progn&#243;stico. Um exame sob estresse adequado e negativo para a presen&#231;a de isquemia mioc&#225;rdica associado &#224; an&#225;lise de PM normal tem excelente evolu&#231;&#227;o, com incid&#234;ncia muito baixa de eventos cardiovasculares graves e &#243;bito no curto a m&#233;dio prazo.<sup><xref ref-type="bibr" rid="B238">238</xref></sup> H&#225; tamb&#233;m uma chance maior de remodelamento ventricular ao longo do tempo, sendo a PM uma vari&#225;vel superior a dados cl&#237;nicos e FEVE para essa predi&#231;&#227;o.<sup><xref ref-type="bibr" rid="B239">239</xref></sup></p>
      <p>A PM tamb&#233;m pode auxiliar na avalia&#231;&#227;o da viabilidade mioc&#225;rdica. Histologicamente, a base da viabilidade do tecido mioc&#225;rdico, que mant&#233;m possibilidade de recupera&#231;&#227;o funcional, est&#225; na rela&#231;&#227;o entre a densidade da microvasculariza&#231;&#227;o e a quantidade/extens&#227;o de col&#225;geno (fibrose) tecidual. Sendo assim, &#225;reas extensas com intenso d&#233;ficit de PM denotam transmuralidade e menor viabilidade mioc&#225;rdica, o que &#233; compar&#225;vel &#224; an&#225;lise da RMC com utiliza&#231;&#227;o de gadol&#237;nio.<sup><xref ref-type="bibr" rid="B240">240</xref>,<xref ref-type="bibr" rid="B241">241</xref></sup></p>
      <p>Recomenda&#231;&#227;o:</p>
      <list list-type="bullet">
        <list-item>
          <p>Nos servi&#231;os com equipe habilitada, a incorpora&#231;&#227;o da ecocardiografia contrastada com an&#225;lise de PM nos exames sob estresse agrega o poder de detec&#231;&#227;o do m&#233;todo para identificar e estratificar DAC obstrutiva;</p>
        </list-item>
        <list-item>
          <p>A PM pode auxiliar na an&#225;lise da viabilidade mioc&#225;rdica de segmentos que claramente n&#227;o melhoram a contra&#231;&#227;o com o teste com dobutamina.</p>
        </list-item>
      </list>
    </sec>
    <sec>
      <title>23. Ecocardiografia de Estresse com <italic>Strain</italic> Mioc&#225;rdico na Cardiopatia Isqu&#234;mica</title>
      <p>A introdu&#231;&#227;o da t&#233;cnica de ecocardiografia com <italic>speckle-tracking</italic> (STE) permite a avalia&#231;&#227;o quantitativa da deforma&#231;&#227;o ou tens&#227;o mioc&#225;rdica durante a ecocardiografia de estresse. A imagem de tens&#227;o fornece uma nova abordagem para a avalia&#231;&#227;o da fun&#231;&#227;o mioc&#225;rdica que &#233; objetiva e quantitativa e tem diversas vantagens sobre a ecocardiografia tradicional. O objetivo desta diretriz &#233; fornecer uma vis&#227;o geral do estado atual do conhecimento sobre a utilidade do GLS ou SLG (<italic>strain</italic> longitudinal global) e do RLS (<italic>strain</italic> regional) na ecocardiografia de estresse, com foco especial na doen&#231;a card&#237;aca isqu&#234;mica.</p>
      <sec>
        <title>23.1. <italic>Strain</italic> Derivado do <italic>Speckle Tracking</italic> Versus <italic>Strain</italic> Baseado no Doppler Tecidual Durante Ecocardiografia de Estresse</title>
        <p>Como mencionado, a ecocardiografia de estresse &#233; uma ferramenta utilizada para avalia&#231;&#227;o da DAC, induzindo estresse fisiol&#243;gico ao cora&#231;&#227;o por meio de exerc&#237;cio ou estimula&#231;&#227;o farmacol&#243;gica com dobutamina ou dipiridamol. A imagem abrangente, que avalia a deforma&#231;&#227;o mioc&#225;rdica, melhora a precis&#227;o da ecocardiografia de estresse no diagn&#243;stico e progn&#243;stico da DAC.</p>
        <p>A imagem de Doppler tecidual e suas derivadas, como a deforma&#231;&#227;o (<italic>strain</italic>) e taxa de deforma&#231;&#227;o mioc&#225;rdica (<italic>strain rate</italic>), fornecem abordagens alternativas para quantificar com mais precis&#227;o a contra&#231;&#227;o regional em repouso ou durante o estresse.<sup><xref ref-type="bibr" rid="B49">49</xref>,<xref ref-type="bibr" rid="B242">242</xref></sup> O Doppler tecidual &#233; vi&#225;vel durante testes de estresse, mas requer uma alta taxa de quadros (<italic>frame rate</italic>), de pelo menos 140 quadros por segundo. No entanto, sua principal limita&#231;&#227;o &#233; que as vari&#225;veis de pico de velocidade e deforma&#231;&#227;o dependem do &#226;ngulo entre o feixe de ultrassom incidente e a parede mioc&#225;rdica. Portanto, a regi&#227;o apical n&#227;o pode ser avaliada<sup><xref ref-type="bibr" rid="B243">243</xref></sup> pela an&#225;lise Doppler.</p>
        <p>A imagem de deforma&#231;&#227;o ou <italic>strain</italic> 2D que n&#227;o envolve Doppler &#233; uma nova t&#233;cnica ecocardiogr&#225;fica usada para medir a deforma&#231;&#227;o e a taxa de deforma&#231;&#227;o. Ela tra&#231;a pontos na imagem de ultrassom para realizar uma an&#225;lise bidimensional do movimento.<sup><xref ref-type="bibr" rid="B244">244</xref></sup></p>
        <p>Os aplicativos de software dispon&#237;veis atualmente permitem o processamento espacial e temporal de imagens, bem como o reconhecimento e a sele&#231;&#227;o de tais pontos (as impress&#245;es digitais do cora&#231;&#227;o) na imagem ecocardiogr&#225;fica. O deslocamento de cada grupo de pontos (pixels) representa o movimento local do tecido. Ao rastrear essas manchas, &#233; poss&#237;vel calcular a velocidade, a deforma&#231;&#227;o e a taxa de deforma&#231;&#227;o do tecido pelo ultrassom bidimensional (2D). A imagem de <italic>strain</italic> 2D sem Doppler &#233; um procedimento simples, que requer apenas a aquisi&#231;&#227;o de um ciclo card&#237;aco e pode ser facilmente processado e interpretado ap&#243;s a aquisi&#231;&#227;o dos dados.<sup><xref ref-type="bibr" rid="B245">245</xref></sup></p>
        <p>A isquemia &#233; definida como uma redu&#231;&#227;o regional no espessamento mioc&#225;rdico, que tamb&#233;m pode resultar em atraso no in&#237;cio e no t&#233;rmino da contra&#231;&#227;o sist&#243;lica.</p>
        <p>Observe que a isquemia n&#227;o &#233; um fen&#244;meno apenas espacial, mas tamb&#233;m temporal. Experimentalmente, com uma oclus&#227;o coron&#225;ria de 40 segundos, o espessamento n&#227;o apenas diminui, mas &#233; retardado e continua no per&#237;odo p&#243;s-eje&#231;&#227;o ou diast&#243;lico (tardocinese, contra&#231;&#227;o p&#243;s-sist&#243;lica ou deforma&#231;&#227;o p&#243;s-sist&#243;lica).</p>
        <p>Infelizmente, o olho humano n&#227;o possui resolu&#231;&#227;o temporal suficiente para detectar altera&#231;&#245;es contr&#225;teis sutis em tempo real. Em compensa&#231;&#227;o, a deforma&#231;&#227;o &#233; rastreada automaticamente durante o ciclo card&#237;aco, medindo a dist&#226;ncia entre dois pixels de um segmento mioc&#225;rdico. Numerosas regi&#245;es pequenas e agrupadas (kernels) s&#227;o sondadas e o programa calcula a m&#233;dia dos seus movimentos antes de extrair curvas regionais e a m&#233;dia global. A qualidade do tra&#231;ado pode ser verificada para cada segmento, com ajuste manual da regi&#227;o se necess&#225;rio. Esse novo m&#233;todo permite a avalia&#231;&#227;o simult&#226;nea dos tr&#234;s componentes da deforma&#231;&#227;o mioc&#225;rdica: radial, longitudinal e circunferencial. Na pr&#225;tica, as incid&#234;ncias apicais s&#227;o usadas para obter o SLG e a taxa de deforma&#231;&#227;o, enquanto as incid&#234;ncias paraesternais de eixo curto s&#227;o usadas para avaliar a deforma&#231;&#227;o radial e circunferencial.<sup><xref ref-type="bibr" rid="B246">246</xref></sup></p>
        <p>Hanekom et al. realizaram um estudo envolvendo 150 pacientes para comparar o uso do <italic>strain</italic> 2D e do Doppler tecidual para detec&#231;&#227;o de isquemia durante ecocardiografia de estresse com dobutamina. O estudo descobriu que a medi&#231;&#227;o do <italic>strain</italic> durante a ecocardiografia de estresse com dobutamina usando imagens de STE &#233; vi&#225;vel e tem precis&#227;o semelhante &#224; do Doppler tecidual na detec&#231;&#227;o de isquemia no territ&#243;rio da ADA esquerda. No entanto, a deforma&#231;&#227;o 2D n&#227;o foi t&#227;o precisa quanto o Doppler tecidual na detec&#231;&#227;o de isquemia nos territ&#243;rios da art&#233;ria circunflexa e art&#233;ria coron&#225;ria direita.<sup><xref ref-type="bibr" rid="B247">247</xref></sup></p>
        <p>Na realidade, n&#227;o h&#225; competi&#231;&#227;o entre o <italic>strain</italic> baseado em Doppler e o <italic>strain</italic> 2D por STE. As vantagens e limita&#231;&#245;es de cada t&#233;cnica se complementam. O <italic>strain</italic> Doppler deve ser usado quando as frequ&#234;ncias card&#237;acas est&#227;o altas, com janelas de qualidade inferior, para avaliar a velocidade basal e medial, e o <italic>strain</italic> 2D quando priorizamos a precis&#227;o e an&#225;lise apical do VE. Recomenda-se o uso do <italic>strain</italic> 2D com frequ&#234;ncias card&#237;acas entre 40 e 100 bpm, com janelas de boa qualidade, para avalia&#231;&#227;o longitudinal e circunferencial do VE, al&#233;m da rota&#231;&#227;o e tor&#231;&#227;o, e priorizar a automaticidade e o menor tempo de estudo.</p>
      </sec>
      <sec>
        <title>23.2. Ecocardiografia de Estresse com <italic>Strain</italic> 2D: Valor Diagn&#243;stico e Progn&#243;stico na Doen&#231;a Arterial Coronariana</title>
        <p>Reant et al. investigaram a aplicabilidade do strain 2D para detec&#231;&#227;o de isquemia durante ecocardiografia de estresse com dobutamina em su&#237;nos. Os principais resultados do estudo demonstraram que o <italic>strain</italic> 2D &#233; t&#227;o confi&#225;vel quanto a sonomicrometria para avalia&#231;&#227;o da fun&#231;&#227;o regional do VE. Os autores demonstraram que anormalidades longitudinais e circunferenciais precedem a diminui&#231;&#227;o da deforma&#231;&#227;o radial na presen&#231;a de isquemia. Essa observa&#231;&#227;o pode ser explicada pelo fato de as fibras mioc&#225;rdicas subendoc&#225;rdicas terem orienta&#231;&#227;o principalmente longitudinal, o que torna a fun&#231;&#227;o longitudinal mais sens&#237;vel &#224; isquemia e, portanto, alterada mais precocemente que a fun&#231;&#227;o radial.<sup><xref ref-type="bibr" rid="B248">248</xref></sup></p>
        <p>Elamragyy et al. realizaram um estudo prospectivo envolvendo 101 pacientes com probabilidade de risco intermedi&#225;rio de DAC. Os pacientes foram avaliados por EED e imagens de STE. Todos os pacientes foram submetidos a angiografia coron&#225;ria dentro de 1 m&#234;s. A sensibilidade e a especificidade da EED para detec&#231;&#227;o de DAC foram de 79,6% e 92,3%, respectivamente. Ao combinar o valor de corte de SLG &#8804; &#8722;20,5, a sensibilidade e a especificidade para o diagn&#243;stico de DAC aumentaram para 95,9% e 84,6%, respectivamente.<sup><xref ref-type="bibr" rid="B249">249</xref></sup></p>
        <p>Outros autores tamb&#233;m demonstraram que SLG durante a EED tem maior sensibilidade, mas menor especificidade em compara&#231;&#227;o com a an&#225;lise da altera&#231;&#227;o da contratilidade parietal.</p>
        <p>O estudo de Uusitalo et al. avaliou o <italic>strain</italic> e o &#237;ndice p&#243;s-sist&#243;lico em 50 pacientes com risco intermedi&#225;rio para DAC ap&#243;s infus&#227;o de dobutamina durante a fase de recupera&#231;&#227;o inicial. Os resultados mostraram um aumento na precis&#227;o diagn&#243;stica do teste. Em pacientes com DAC, observou-se que o <italic>strain</italic> foi de &#8722;16,4 &#177; 4,8, comparado com &#8722;19,3 &#177; 3,9 em indiv&#237;duos normais (p &lt; 0,001) com aumento significativo no &#237;ndice p&#243;s-sist&#243;lico.<sup><xref ref-type="bibr" rid="B250">250</xref></sup></p>
        <p>Os resultados do estudo de Uusitalo et al. sugerem que a incorpora&#231;&#227;o de medi&#231;&#245;es de tens&#227;o e &#237;ndice p&#243;s-sist&#243;lico durante a recupera&#231;&#227;o precoce ap&#243;s a infus&#227;o de 20 mcg/kg/min de dobutamina pode melhorar a precis&#227;o diagn&#243;stica do EED em pacientes com risco intermedi&#225;rio para DAC.</p>
        <p>Embora os estudos de viabilidade sejam controversos, uma grande literatura sustenta que o comportamento do SLG e do SPI &#233; capaz de reconhecer o mioc&#225;rdio vi&#225;vel de acordo com a resposta a baixas doses de dobutamina.</p>
        <p>Imagens de <italic>strain</italic> durante a EED s&#227;o mais f&#225;ceis de obter em compara&#231;&#227;o com a ecocardiografia de exerc&#237;cio porque s&#227;o menos afetadas pelo movimento respirat&#243;rio. A EED tamb&#233;m permite uma aquisi&#231;&#227;o de imagem mais consistente, devido ao aumento est&#225;vel da FC e da contratilidade, o que pode melhorar a precis&#227;o e a confiabilidade das medidas de deforma&#231;&#227;o mioc&#225;rdica.</p>
        <p>Imagens de <italic>strain</italic> durante a EED t&#234;m sido estudadas extensivamente, mas faltam resultados sobre a viabilidade e a aplicabilidade da imagem durante a ecocardiografia com exerc&#237;cio. Isso pode se dever a dificuldades t&#233;cnicas associadas &#224; aquisi&#231;&#227;o de imagens durante o exerc&#237;cio, bem como ao aumento do movimento do paciente e artefatos respirat&#243;rios que podem afetar a precis&#227;o das medidas de esfor&#231;o.</p>
        <p>Atualmente, existem poucos dados e apenas pequenas s&#233;ries que comparam a aquisi&#231;&#227;o de imagens convencionais com o uso de GLS e RLS durante ecocardiografia de estresse em esteira ou bicicleta supina.</p>
        <p>A viabilidade da ecocardiografia de estresse com exerc&#237;cio foi avaliada em 67 pacientes adultos saud&#225;veis, com resultados satisfat&#243;rios. O estudo analisou pacientes por faixa et&#225;ria e sexo, com grupos divididos nas faixas et&#225;rias de 23 a 35, 35 a 55 e 55 a 80 anos. Os resultados mostraram que o SLG ou GLS aumentou significativamente durante o exerc&#237;cio em todas as faixas et&#225;rias, independentemente do sexo. O aumento absoluto m&#233;dio na deforma&#231;&#227;o longitudinal global foi de 5,3%.<sup><xref ref-type="bibr" rid="B251">251</xref></sup> Isso sugere que a ecocardiografia de esfor&#231;o pode ser uma ferramenta &#250;til para avaliar a fun&#231;&#227;o card&#237;aca durante o teste de esfor&#231;o.</p>
        <p>Atualmente, &#233; poss&#237;vel demonstrar, em pacientes selecionados, com boa janela, a alta viabilidade para an&#225;lise do SLG em repouso (99%) e no p&#243;s-estresse (esfor&#231;o) imediato, antes dos 30 segundos (97,5%) em bicicleta supina. A aus&#234;ncia de aumento ou diminui&#231;&#227;o da deforma&#231;&#227;o longitudinal dos segmentos apicais foi concordante com a presen&#231;a de isquemia detectada visualmente em 78,6% dos estudos, enquanto em 96,2% dos casos em que a isquemia foi negativa pelos crit&#233;rios de anormalidade parietal subjetiva pela avalia&#231;&#227;o padr&#227;o, a deforma&#231;&#227;o longitudinal apical aumentou.</p>
        <p>No entanto, o exame somente era confi&#225;vel para segmentos relacionados ao territ&#243;rio da ADA. Assim, a an&#225;lise do <italic>strain</italic> 2D foi vi&#225;vel no per&#237;odo p&#243;s-esfor&#231;o imediato, mas as altas frequ&#234;ncias card&#237;acas foram respons&#225;veis pelos resultados inespec&#237;ficos nos segmentos medial e basal &#237;nfero-p&#243;stero-lateral.<sup><xref ref-type="bibr" rid="B252">252</xref></sup></p>
        <p>As principais raz&#245;es pelas quais apenas os segmentos apicais puderam ser analisados foram, possivelmente: 1) A resolu&#231;&#227;o axial 2D &#233; geralmente muito boa. 2) A resolu&#231;&#227;o lateral diminui &#224; medida que a profundidade de campo aumenta. Se a resolu&#231;&#227;o lateral &#233; baixa, a consequ&#234;ncia &#233; uma imagem "borrada", que n&#227;o permite que os pixels sejam seguidos t&#227;o facilmente nos campos distantes. 3) Com os movimentos translacionais do cora&#231;&#227;o durante o exerc&#237;cio, a dificuldade de rastreamento dos segmentos basal e medial aumenta. 4) Com a FC elevada, as mudan&#231;as de quadro a quadro s&#227;o abruptas e a independ&#234;ncia angular come&#231;a a ser perdida com uma densidade de linha (e de informa&#231;&#227;o) menor, suficiente para rastreamento no campo pr&#243;ximo, mas n&#227;o para o campo distante.<sup><xref ref-type="bibr" rid="B252">252</xref></sup></p>
        <p>Entre os exames dispon&#237;veis, a ecocardiografia de estresse com dipiridamol (EEDIP) &#233; uma das t&#233;cnicas recomendadas para o diagn&#243;stico e progn&#243;stico da DAC. A sua utiliza&#231;&#227;o em diferentes laborat&#243;rios n&#227;o &#233; generalizada por falta de conhecimento ou por raz&#245;es pessoais, geogr&#225;ficas, econ&#244;micas ou de disponibilidade, e n&#227;o por motivos cient&#237;ficos de fato. Sua utiliza&#231;&#227;o de acordo com o estado de arte da t&#233;cnica, em altas doses e curto tempo de infus&#227;o com adi&#231;&#227;o de atropina e/ou <italic>handgrip,</italic> permite um n&#237;vel de acur&#225;cia diagn&#243;stica semelhante &#224; da EED, com taxa de complica&#231;&#245;es graves tr&#234;s vezes menor.<sup><xref ref-type="bibr" rid="B57">57</xref>,<xref ref-type="bibr" rid="B253">253</xref></sup></p>
        <p>No estudo retrospectivo de Lowenstein-Haber et al. envolvendo 150 pacientes encaminhados para EEDIP, foram avaliadas a reserva coronariana (RC) apical e da ADA e an&#225;lise visual da motilidade parietal.<sup><xref ref-type="bibr" rid="B254">254</xref></sup> <italic>Strain</italic> regional apical anormal durante ecocardiografia com dipiridamol, bem como baixa RC, foram os &#250;nicos preditores de pior resultado na progress&#227;o, independentemente da an&#225;lise visual da anormalidade parietal.</p>
        <p>Um relat&#243;rio anterior do mesmo grupo tamb&#233;m demonstrou que a an&#225;lise de deforma&#231;&#227;o 2D melhorou significativamente a sensibilidade da EEDIP para a detec&#231;&#227;o de DAC em rela&#231;&#227;o &#224; an&#225;lise de contratilidade padr&#227;o (83,3% vs. 50%; p = 0,001), sem comprometer sua especificidade (100%).<sup><xref ref-type="bibr" rid="B255">255</xref></sup></p>
        <p>Os estudos de outros grupos que tamb&#233;m comprovaram o valor aditivo da medi&#231;&#227;o de deforma&#231;&#227;o bidimensional &#224; an&#225;lise visual tradicional do escore parietal permitem conclus&#245;es id&#234;nticas.</p>
      </sec>
      <sec>
        <title>23.3. Qual <italic>Strain</italic> Pode Ser &#218;til na Ecocardiografia de Estresse: Global ou Regional, Longitudinal ou Circunferencial? E Qual a Import&#226;ncia do Espessamento P&#243;s-Sist&#243;lico?</title>
        <p>A maioria dos estudos que avaliaram a viabilidade e a acur&#225;cia do SLG durante a ecocardiografia de exerc&#237;cio inclui pequenos grupos de indiv&#237;duos saud&#225;veis.</p>
        <p>Embora a an&#225;lise RLS possa fornecer informa&#231;&#245;es mais detalhadas sobre &#225;reas espec&#237;ficas do cora&#231;&#227;o, esta tamb&#233;m pode ser tecnicamente mais dif&#237;cil e complicada de realizar e interpretar. Por outro lado, o SLG facilita a avalia&#231;&#227;o mais completa da fun&#231;&#227;o mioc&#225;rdica global e tem se demonstrado um preditor poderoso de resultados cardiovasculares adversos.</p>
        <p>No entanto, tamb&#233;m &#233; importante notar que a mera observa&#231;&#227;o da amplitude da deforma&#231;&#227;o pode n&#227;o refletir toda a pesquisa. O momento do pico de deforma&#231;&#227;o, tanto global quanto regionalmente (porcentagens de contra&#231;&#227;o e deforma&#231;&#227;o p&#243;s-sist&#243;lica e &#237;ndices de dispers&#227;o mec&#226;nica), s&#227;o fundamentais e podem fornecer informa&#231;&#245;es sobre anormalidades na mec&#226;nica mioc&#225;rdica, como visto no exemplo a seguir (<xref ref-type="fig" rid="f29">Figuras 23.1</xref> e <xref ref-type="fig" rid="f30">23.2</xref>).</p>
        <fig id="f29">
          <label>Figura 23.1</label>
          <caption>
            <title>Homem de 50 anos com fatores de risco positivos e dor interescapular no in&#237;cio do exerc&#237;cio. Diminui&#231;&#227;o da tens&#227;o e da deforma&#231;&#227;o p&#243;s-sist&#243;lica no pico do exerc&#237;cio (setas brancas). Angiografia coron&#225;ria: duas obstru&#231;&#245;es significativas em conjunto na art&#233;ria descendente anterior.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <fig id="f30">
          <label>Figura 23.2</label>
          <caption>
            <title>Strain global com pouco aumento com dobutamina, mas dispers&#227;o acentuada das curvas e contra&#231;&#227;o p&#243;s-sist&#243;lica como sinal de isquemia. Canto superior esquerdo: mapa polar com strain basal de 21,6%. M&#233;dio: Strain &#224; ecocardiografia de esfor&#231;o com dobutamina 21,4%. Direita: Strain na recupera&#231;&#227;o 20,8%. Linha do meio: Em azul, a porcentagem de strain p&#243;s-sist&#243;lico que aumentou acentuadamente com baixas doses de dobutamina. Abaixo das respectivas curvas. Paciente com doen&#231;a arterial coronariana grave triarterial.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>A ecocardiografia de estresse com dipiridamol &#233; uma excelente combina&#231;&#227;o para avaliar simultaneamente a movimenta&#231;&#227;o da parede e o comportamento do SLG e do SPI, acrescentando informa&#231;&#245;es diagn&#243;sticas e progn&#243;sticas. GLS e RLS com dobutamina aumentam a precis&#227;o para detectar a viabilidade e o <italic>strain rate</italic>, enquanto Doppler (modo M) pode ser de grande ajuda para visualizar o fen&#244;meno da contra&#231;&#227;o p&#243;s-sist&#243;lica, que tamb&#233;m pode ser visualizado nas curvas e no alvo com <italic>strain</italic> 2D, mostrando dissincronismo/isquemia caso apare&#231;a durante o teste.</p>
        <p>O estabelecimento de valores normais para o <italic>strain</italic> no estresse em indiv&#237;duos saud&#225;veis pode ajudar a interpretar melhor os dados de <italic>strain</italic> em pacientes com suspeita de doen&#231;a cardiovascular.<sup><xref ref-type="bibr" rid="B256">256</xref></sup></p>
        <p>O SLG no VE n&#227;o &#233; homog&#234;neo e h&#225; um gradiente dos segmentos basais ao &#225;pice. Conhecido como gradiente basal-apical, &#233; observado tanto no <italic>strain</italic> circunferencial quanto no longitudinal, com menores valores nos segmentos basais e maiores valores no &#225;pice. Tamb&#233;m foi encontrado gradiente entre o subendoc&#225;rdio e o epic&#225;rdio.</p>
        <p>Embora a literatura forne&#231;a valores de refer&#234;ncia para os segmentos apical, m&#233;dio-ventricular e basal, a falta de homogeneidade da deforma&#231;&#227;o regional complica as an&#225;lises posteriores. Contudo, a an&#225;lise da deforma&#231;&#227;o regional pode ajudar a confirmar a isquemia na ecocardiografia de estresse.</p>
        <p>Tr&#234;s cortes de eixo curto nos n&#237;veis basal, m&#233;dio-ventricular e apical devem ser usados para avaliar a deforma&#231;&#227;o circunferencial e o twist e tor&#231;&#227;o. Por&#233;m, a aquisi&#231;&#227;o do &#225;pice id&#234;ntico &#224; imagem basal em repouso nem sempre &#233; vi&#225;vel durante a ecocardiografia de estresse, tornando-a menos adequada para esse tipo de avalia&#231;&#227;o.</p>
      </sec>
      <sec>
        <title>23.4. O <italic>Strain</italic> Tem Mem&#243;ria Isqu&#234;mica?</title>
        <p>Em um estudo com 101 pacientes com comportamento isqu&#234;mico segundo an&#225;lise visual, o SLG m&#233;dio em repouso foi de &#8722;22,3 &#177; 4,3%; diminuindo significativamente no pico do exerc&#237;cio para &#8722;16 &#177; 3,2%; 3 minutos ap&#243;s a recupera&#231;&#227;o, os pacientes apresentaram valores superiores aos obtidos em repouso, &#8722;24,3 &#177; 5,1%. Com isso, as altera&#231;&#245;es do SLG e do SPI n&#227;o persistiram ap&#243;s a recupera&#231;&#227;o dos dist&#250;rbios de motilidade segmentar analisados visualmente.<sup><xref ref-type="bibr" rid="B257">257</xref></sup></p>
        <p>Esse comportamento &#233; consistente com um estudo experimental da Universidade de Osaka que comprovou que a recupera&#231;&#227;o da deforma&#231;&#227;o e da taxa de deforma&#231;&#227;o foi r&#225;pida e completa (em rela&#231;&#227;o ao tempo de oclus&#227;o). No entanto, os &#237;ndices p&#243;s-sist&#243;licos foram mais duradouros.</p>
        <p>A conclus&#227;o &#233; que se a an&#225;lise do SLG e do SPI for realizada v&#225;rios minutos ap&#243;s o exerc&#237;cio, com frequ&#234;ncias inferiores a 100 bpm, quando n&#227;o h&#225; mais dist&#250;rbios de contratilidade e o tempo de isquemia foi curto, a distens&#227;o se recupera rapidamente, mesmo em valores supernormais (<xref ref-type="fig" rid="f31">Figuras 23.3</xref> e <xref ref-type="fig" rid="f32">23.4</xref>).</p>
        <fig id="f31">
          <label>Figura 23.3</label>
          <caption>
            <title>Mulher de 57 anos com angina est&#225;vel. Strain longitudinal global normal em repouso com dissinergias m&#250;ltiplas e extensas em baixa carga, deteriora&#231;&#227;o do pico de strain longitudinal e deforma&#231;&#227;o p&#243;s-sist&#243;lica significativa: Angiografia coron&#225;ria: Obstru&#231;&#227;o grave distal do tronco principal esquerdo: Art&#233;ria descendente anterior, Art&#233;rias coron&#225;rias direita e circunflexa com obstru&#231;&#245;es graves. Strain longitudinal global em repouso: 19,5% Exerc&#237;cio: 9,5%.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <fig id="f32">
          <label>Figura 23.4</label>
          <caption>
            <title>Paciente de 65 anos. Ecocardiografia de estresse positivo com isquemia nos segmentos apical, septal anterior, anterior e inferior com strain longitudinal global no in&#237;cio &#8722;20,7%, pico &#8722;12,6% e ap&#243;s 3 minutos de recupera&#231;&#227;o &#8722;21,1%. Angiografia coron&#225;ria: Obstru&#231;&#245;es graves das art&#233;rias coron&#225;rias direita e descendente anterior. Exemplo de que o esfor&#231;o em repouso n&#227;o prev&#234; o resultado da ecocardiografia de estresse e n&#227;o possui mem&#243;ria isqu&#234;mica.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>Esse comportamento transit&#243;rio explica por que pacientes com angina e sem dist&#250;rbios de motilidade apresentam um estiramento 2D em repouso na faixa normal fora do epis&#243;dio de dor (se de curta dura&#231;&#227;o).</p>
      </sec>
      <sec>
        <title>23.5. O <italic>Strain</italic> Longitudinal Global Basal Pode Predizer Doen&#231;a Arterial Coronariana na Aus&#234;ncia de Anormalidade Parietal Visual sob Estresse?</title>
        <p>H&#225; relatos de que o SLG em repouso &#233; preditor da presen&#231;a de doen&#231;a coronariana do tronco principal esquerdo e de doen&#231;a triarterial em pacientes sem anormalidades na motilidade regional. De acordo com o estudo de Jin-Oh Choi et al., o <italic>strain</italic> 2D global foi menor em 108 pacientes com doen&#231;a triarterial ou do tronco principal esquerdo, mesmo sem anormalidades de contratilidade (com ponto de corte de &#8722;17,9%) com sensibilidade e especificidade de 79% em rela&#231;&#227;o ao normal.<sup><xref ref-type="bibr" rid="B258">258</xref></sup></p>
        <p>O estudo de Montgomery relata que a an&#225;lise do SLG pode detectar DAC moderada e grave compar&#225;vel ao resultado da an&#225;lise visual durante a ecocardiografia de estresse. Os autores afirmam que o SLG inferior a &#8722;20% tem valor preditivo negativo de 80% para les&#245;es &gt; 50% e de 90% para les&#245;es &gt; 70%.<sup><xref ref-type="bibr" rid="B255">255</xref></sup></p>
        <p>Por outro lado, em um grupo de 124 pacientes sem dist&#250;rbios contr&#225;teis em repouso submetidos a cineangiocoronariografia, o SLG n&#227;o permitiu prever o resultado da ecocardiografia de estresse nem a presen&#231;a de DAC significativa.<sup><xref ref-type="bibr" rid="B260">260</xref></sup></p>
      </sec>
      <sec>
        <title>23.6. Limita&#231;&#245;es</title>
        <p>Embora a imagem de <italic>strain</italic> 2D durante a ecocardiografia de estresse tenha demonstrado seu benef&#237;cio na detec&#231;&#227;o de altera&#231;&#245;es sutis na fun&#231;&#227;o ventricular esquerda, seu uso apresenta diversas limita&#231;&#245;es. Fatores t&#233;cnicos como qualidade de imagem, movimento respirat&#243;rio e posi&#231;&#227;o do paciente podem afetar a precis&#227;o e a reprodutibilidade das medidas de <italic>strain</italic>. Al&#233;m disso, atualmente n&#227;o existe um m&#233;todo padronizado para an&#225;lise de <italic>strain</italic> na ecocardiografia de estresse, o que pode limitar a comparabilidade e aumentar a variabilidade dos resultados entre os diferentes estudos.</p>
        <p>Embora a experi&#234;ncia tenha mostrado resultados promissores, estudos maiores s&#227;o necess&#225;rios para estabelecer a acur&#225;cia diagn&#243;stica, a sensibilidade e a especificidade da imagem com <italic>strain</italic> na detec&#231;&#227;o de isquemia mioc&#225;rdica durante o exerc&#237;cio.</p>
        <p>Ademais, a integra&#231;&#227;o das medidas de <italic>strain</italic> somadas a outros par&#226;metros obtidos durante a ecocardiografia de estresse, como a an&#225;lise visual de anormalidades parietais, linhas B, reserva diast&#243;lica, reserva contr&#225;til e reserva cronotr&#243;pica, que &#233; a verdadeira arte da ecocardiografia de estresse, n&#227;o &#233; realizada na maioria dos laborat&#243;rios do mundo, e sua utilidade est&#225; confirmada para diferentes doen&#231;as card&#237;acas, como demonstram os resultados do estudo Stress 2030 liderado pelo Dr. Eugenio Picano et al.<sup><xref ref-type="bibr" rid="B261">261</xref></sup></p>
        <p>&#201; conveniente ter em conta que o resultado dessas novas t&#233;cnicas tamb&#233;m depende do operador e que s&#227;o necess&#225;rias tecnologia, experi&#234;ncia e forma&#231;&#227;o adequadas para a sua utiliza&#231;&#227;o racional. Com experi&#234;ncia, tecnologia adequada e excelente qualidade de imagem, essa limita&#231;&#227;o n&#227;o &#233; t&#227;o cr&#237;tica para a ecocardiografia de estresse.</p>
        <p>A FC elevada dificulta a an&#225;lise do estiramento 2D no exerc&#237;cio e com altas doses de dobutamina, pois a resolu&#231;&#227;o temporal tem dificuldade de rastrear os pixels dos segmentos basal e m&#233;dio do mioc&#225;rdio.</p>
        <p>Embora a imagem de <italic>strain</italic> tenha mostrado benef&#237;cios em potencial na ecocardiografia de estresse, incluindo maior precis&#227;o na detec&#231;&#227;o de isquemia mioc&#225;rdica e identifica&#231;&#227;o de disfun&#231;&#227;o ventricular esquerda subcl&#237;nica em pacientes assintom&#225;ticos, ainda ser&#225; necess&#225;rio realizar um trabalho de pesquisa consider&#225;vel para definir completamente seu papel na pr&#225;tica cl&#237;nica de rotina.</p>
      </sec>
    </sec>
    <sec>
      <title>24. Ecocardiografia de Estresse com <italic>Strain</italic> Mioc&#225;rdico para Al&#233;m da Cardiopatia Isqu&#234;mica</title>
      <p>Uma das aplica&#231;&#245;es do SLG durante a ecocardiografia de estresse &#233; a determina&#231;&#227;o da reserva contr&#225;til (RC), que complementa as informa&#231;&#245;es fornecidas pela varia&#231;&#227;o da FE. A resposta normal &#233; o incremento de dois pontos absolutos do SLG do VE durante o estresse em compara&#231;&#227;o com o repouso.<sup><xref ref-type="bibr" rid="B262">262</xref></sup></p>
      <p>Na regurgita&#231;&#227;o mitral prim&#225;ria moderada ou mais grave sem disfun&#231;&#227;o ventricular, Magne et al. demonstraram que a aus&#234;ncia de RC por SLG &#224; ecocardiografia de estresse de exerc&#237;cio &#233; um preditor importante e independente de eventos card&#237;acos futuros.<sup><xref ref-type="bibr" rid="B128">128</xref></sup></p>
      <p>Um estudo interessante de Arbucci et al. demonstrou que a aus&#234;ncia de RC por SLG durante a ecocardiografia de estresse de exerc&#237;cio, em pacientes assintom&#225;ticos com estenose a&#243;rtica importante, est&#225; associada a uma maior taxa de eventos e menor sobrevida. Al&#233;m disso, a avalia&#231;&#227;o de RC por SLG foi o melhor preditor de eventos em compara&#231;&#227;o com a medida tradicional, a avalia&#231;&#227;o de RC por FE.<sup><xref ref-type="bibr" rid="B263">263</xref></sup></p>
      <p>Na estenose a&#243;rtica de baixo fluxo e baixo gradiente com FE reduzida, a avalia&#231;&#227;o de SLG de repouso e durante a ecocardiografia de estresse com dobutamina adiciona informa&#231;&#245;es progn&#243;sticas importantes aos par&#226;metros ecocardiogr&#225;ficos tradicionais. Conforme demonstrado por Dahou et al., SLG inferior a 9% em repouso e inferior a 10% ao estresse est&#225; associado a maior mortalidade tanto em pacientes tratados conservadoramente quanto &#224;queles submetidos a interven&#231;&#245;es.<sup><xref ref-type="bibr" rid="B264">264</xref></sup></p>
      <p>A diferencia&#231;&#227;o entre cardiomiopatia isqu&#234;mica e n&#227;o isqu&#234;mica na presen&#231;a de disfun&#231;&#227;o ventricular importante &#233; um desafio para a ecocardiografia de estresse. Muitas vezes, a avalia&#231;&#227;o anat&#244;mica &#233; imprescind&#237;vel. No entanto, em pacientes com disfun&#231;&#227;o leve ou moderada do VE, o incremento sustentado da contratilidade e do SLG sugere a presen&#231;a de cardiomiopatia n&#227;o isqu&#234;mica.<sup><xref ref-type="bibr" rid="B99">99</xref></sup> Vale ressaltar que essa resposta tamb&#233;m &#233; observada em atletas durante a ecocardiografia de estresse, em geral com incremento supranormal da deforma&#231;&#227;o, sendo de grande valor na distin&#231;&#227;o entre o cora&#231;&#227;o do atleta e cardiomiopatias.<sup><xref ref-type="bibr" rid="B265">265</xref>,<xref ref-type="bibr" rid="B266">266</xref></sup></p>
      <p>Na cardiomiopatia hipertr&#243;fica, o uso do SLG durante a ecocardiografia de estresse auxilia na identifica&#231;&#227;o de pacientes sob maior risco cardiovascular. Al&#233;m da aus&#234;ncia de RC, a presen&#231;a de dissincronia ao exerc&#237;cio tamb&#233;m &#233; um par&#226;metro relevante a ser analisado nessa popula&#231;&#227;o.<sup><xref ref-type="bibr" rid="B267">267</xref></sup></p>
      <p>A maior dificuldade do uso do SLG durante a ecocardiografia de estresse &#233; a diferencia&#231;&#227;o entre a redu&#231;&#227;o patol&#243;gica da deforma&#231;&#227;o e a redu&#231;&#227;o secund&#225;ria devido &#224;s limita&#231;&#245;es inerentes &#224; t&#233;cnica. Taquicardia, hiperventila&#231;&#227;o, imagem inadequada, variabilidade de resultados entre os aplicativos de software e inexperi&#234;ncia com o m&#233;todo s&#227;o alguns dos desafios para o emprego do <italic>strain</italic> no estresse (<xref ref-type="table" rid="t22">Tabela 24.1</xref>), como mencionado anteriormente.</p>
      <table-wrap id="t22">
        <label>Tabela 24.1</label>
        <caption>
          <title>Lista de limita&#231;&#245;es do uso do strain longitudinal global durante a ecocardiografia de estresse e as poss&#237;veis solu&#231;&#245;es a serem adotadas</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 style="background-color:#76B4CF">
              <th align="left" valign="middle">Problemas</th>
              <th align="center" valign="middle">Solu&#231;&#245;es</th>
            </tr>
          </thead>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr>
              <td align="left" valign="middle">Tempo adicional &#224; ecocardiografia de estresse/necessidade de aquisi&#231;&#227;o de imagens adicionais</td>
              <td align="center" valign="middle">Utilizar de rotina os tr&#234;s cortes apicais no protocolo de estresse</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">Imagem inadequada</td>
              <td align="center" valign="middle">Ajuste adequado da profundidade, largura do setor e taxa de quadros (&gt; 60 qps)<break/> Evitar a aquisi&#231;&#227;o de clipes com variabilidade de FC superior a 10%<break/> Verificar a qualidade do ECG e evitar a aquisi&#231;&#227;o de clipes extrassist&#243;licos/p&#243;s-extrassist&#243;licos</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Frequ&#234;ncia card&#237;aca elevada</td>
              <td align="center" valign="middle">Utilizar imagens de recupera&#231;&#227;o imediata, dentro do primeiro minuto p&#243;s esfor&#231;o, na ecocardiografia de estresse f&#237;sico.</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN12">
            <p>ECG: eletrocardiograma; FC: frequ&#234;ncia card&#237;aca.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>Na doen&#231;a n&#227;o isqu&#234;mica, valoriza-se mais o valor global do que o valor regional da deforma&#231;&#227;o, o que facilita seu emprego na pr&#225;tica. A influ&#234;ncia negativa da taquicardia e da hiperventila&#231;&#227;o na avalia&#231;&#227;o da deforma&#231;&#227;o durante a EEF pode ser reduzida com a utiliza&#231;&#227;o de imagens de recupera&#231;&#227;o imediata (at&#233; o primeiro minuto ap&#243;s o t&#233;rmino do exerc&#237;cio). O estresse com dipiridamol, por sua menor influ&#234;ncia cronotr&#243;pica e alta qualidade de imagem bidimensional, facilita consideravelmente a avalia&#231;&#227;o do SLG.</p>
      <p>O uso do <italic>strain</italic> se tornou frequente na pr&#225;tica cl&#237;nica e deve ser adotado sempre que poss&#237;vel. O car&#225;ter quantitativo, independente e objetivo o transformam em uma ferramenta promissora e que deve ser incorporada &#224; ecocardiografia de estresse.</p>
      <p>Atualmente, a utilidade do SLG do VE para avalia&#231;&#227;o da RC se tornou importante. Independentemente da patologia estudada, a aus&#234;ncia de RC est&#225; associada a pior evolu&#231;&#227;o cl&#237;nica e maior taxa de eventos. A factibilidade da avalia&#231;&#227;o da RC com SLG durante a ecocardiografia de estresse &#233; maior em estudos com vasodilatador, seguido da dobutamina e, por fim, do exerc&#237;cio.</p>
    </sec>
    <sec>
      <title>25. Ecocardiografia de Estresse Tridimensional</title>
      <sec>
        <title>25.1. A Tecnologia da Ecocardiografia Tridimensional e sua Aplica&#231;&#227;o na Imagem do Ecocardiograma</title>
        <p>A ecocardiografia tridimensional permite a visualiza&#231;&#227;o em tempo real de cinco dimens&#245;es f&#237;sicas das estruturas card&#237;acas, considerando-se os tr&#234;s planos ortogonais de defini&#231;&#227;o anat&#244;mica, o plano dos fluxos card&#237;acos e o plano do dimensionamento temporal.<sup><xref ref-type="bibr" rid="B268">268</xref>-<xref ref-type="bibr" rid="B271">271</xref></sup> Dessa forma, a t&#233;cnica acrescenta informa&#231;&#245;es morfofuncionais importantes em compara&#231;&#227;o com as informa&#231;&#245;es derivadas da an&#225;lise ecocardiogr&#225;fica bidimensional.<sup><xref ref-type="bibr" rid="B268">268</xref>-<xref ref-type="bibr" rid="B271">271</xref></sup> As primeiras imagens relacionadas &#224; ultrassonografia tridimensional (3D) datam da d&#233;cada de 50, em que o interesse estava direcionado &#224; observa&#231;&#227;o da &#243;rbita humana. Na d&#233;cada de 70, foram realizadas as primeiras imagens das estruturas card&#237;acas. A partir de ent&#227;o, ocorreram diversos incrementos e avan&#231;os na observa&#231;&#227;o ecocardiogr&#225;fica card&#237;aca tridimensional<sup><xref ref-type="bibr" rid="B48">48</xref>,<xref ref-type="bibr" rid="B272">272</xref>-<xref ref-type="bibr" rid="B281">281</xref></sup> at&#233; chegarmos ao momento atual, em que &#233; poss&#237;vel realizar uma an&#225;lise matricial multiangular tridimensional do cora&#231;&#227;o em tempo real. Isso foi poss&#237;vel gra&#231;as &#224; nanotecnologia, &#224; observa&#231;&#227;o digital estrutural e ao avan&#231;o indiscut&#237;vel da velocidade de an&#225;lise morfofuncional com o desenvolvimento de algoritmos dedicados a identifica&#231;&#227;o matricial e dos elementos volum&#233;tricos de imagem (voxels). A an&#225;lise simult&#226;nea em tempo real de m&#250;ltiplos planos de observa&#231;&#227;o estrutural do cora&#231;&#227;o se encaixa perfeitamente na ecocardiografia de estresse, possibilitando a realiza&#231;&#227;o de exames em menor de tempo de aquisi&#231;&#227;o, com grande reprodutibilidade, pequena varia&#231;&#227;o interobservador, proporcionando ainda a identifica&#231;&#227;o estrutural a partir de novas proje&#231;&#245;es espaciais.<sup><xref ref-type="bibr" rid="B48">48</xref>,<xref ref-type="bibr" rid="B272">272</xref>-<xref ref-type="bibr" rid="B281">281</xref></sup> A aquisi&#231;&#227;o tridimensional tamb&#233;m permite a redu&#231;&#227;o do encurtamento espacial das imagens (<italic>foreshortening</italic>) durante a sua aquisi&#231;&#227;o, situa&#231;&#227;o que pode ocorrer durante o emprego da ecocardiografia bidimensional. Atualmente, a ecocardiografia de estresse 3D pode ser realizada a partir de imagem biplanar guiada por observa&#231;&#227;o tridimensional (<italic>full-volume</italic>) ou a partir de imagem matricial (<italic>X-plane</italic>). A an&#225;lise ecocardiogr&#225;fica de estresse 3D depende sobretudo da qualidade da imagem inicial, sendo amplificada com a associa&#231;&#227;o de ARUS. Contudo, o emprego de ARUS pode ocasionar uma redu&#231;&#227;o da resolu&#231;&#227;o temporal, que j&#225; apresenta limita&#231;&#227;o ao 3D, apesar da melhora consider&#225;vel da defini&#231;&#227;o das bordas endoc&#225;rdicas em estudos de estresse 3D com imagem em harm&#244;nica e qualidade sub&#243;tima.<sup><xref ref-type="bibr" rid="B278">278</xref></sup> Por esse motivo, seu uso junto ao estresse 3D ainda n&#227;o &#233; amplamente recomendado. Observamos que a aquisi&#231;&#227;o em imagem bidimensional permite a an&#225;lise com maior n&#250;mero de quadros (maior <italic>frame rate</italic>) e a an&#225;lise da perfus&#227;o mioc&#225;rdica (quando utilizada com ARUS) tamb&#233;m utiliza o <italic>frame rate</italic>, por&#233;m menor, enquanto a an&#225;lise 3D propicia a avalia&#231;&#227;o a partir de maior volume de amostra (<italic>3D Full-volume</italic>), ou de an&#225;lise biplanar em tempo real (<italic>3D-X-plane</italic>). No entanto, a an&#225;lise em <italic>3D Full-volume</italic> pode redundar em artefatos de aquisi&#231;&#227;o (<italic>stitch</italic>) por movimento de transla&#231;&#227;o dos voxels e apresenta baixas taxas de repeti&#231;&#227;o dos voxels e baixa resolu&#231;&#227;o temporal e espacial (<italic>3D Full-volume</italic>), o que limita a an&#225;lise da perfus&#227;o mioc&#225;rdica. Em compara&#231;&#227;o, an&#225;lise em 3D matricial (<italic>X-plane</italic>) apresenta melhor taxa de repeti&#231;&#227;o dos quadros.</p>
        <p>Novos modelos de equipamentos de ecocardiografia est&#227;o sendo disponibilizados para a pr&#225;tica cl&#237;nica, com a possibilidade de usar transdutores e algoritmos que permitem melhor qualidade da imagem, com <italic>volume rate</italic> tridimensional mais elevado, ampliando a sua realiza&#231;&#227;o futura.</p>
        <p>Como modelos de realiza&#231;&#227;o do estresse 3D, podemos empregar a an&#225;lise multiplanar 3D com a observa&#231;&#227;o simult&#226;nea do eixo longo longitudinal e do eixo curto do VE e de dados volum&#233;tricos das proje&#231;&#245;es apicais. A imagem para aquisi&#231;&#227;o em 3D apical <italic>Full-Volume</italic> deve ser realizada com o transdutor em posi&#231;&#227;o apical (&#225;pex do VE), com o paciente em apneia durante a aquisi&#231;&#227;o (para a minimiza&#231;&#227;o do <italic>stitching</italic> eventual das imagens, derivado da transla&#231;&#227;o card&#237;aca), com o volume de amostragem largo o suficiente para a an&#225;lise de todo o VE, por&#233;m sem que ocorra excesso de abertura do setor (que redunda em menor volume rate), e com o registro do ECG. Caso ocorram arritmias, como a fibrila&#231;&#227;o atrial, isso pode ocasionar erros na an&#225;lise 3D. A hiperventila&#231;&#227;o durante a aquisi&#231;&#227;o da imagem tamb&#233;m pode representar dificuldades &#224; obten&#231;&#227;o da melhor qualidade de imagem.</p>
        <p>Para o futuro, a ecocardiografia de estresse 3D estar&#225; relacionada ao emprego de novos algoritmos de interpreta&#231;&#227;o de imagem e de transdutores menores, com a aquisi&#231;&#227;o das imagens a partir de um batimento card&#237;aco &#250;nico, com maior n&#250;mero de voxels. Isso levar&#225; a melhor qualidade das imagens, sobretudo da qualidade da imagem lateral, o que por sua vez levar&#225; &#224; redu&#231;&#227;o do fen&#244;meno de <italic>stitching</italic> e ao menor tempo de realiza&#231;&#227;o do exame.</p>
      </sec>
      <sec>
        <title>25.2. A Aplica&#231;&#227;o da Ecocardiografia Tridimensional Junto &#224; Ecocardiografia de Estresse</title>
        <p>A escolha da aplica&#231;&#227;o de imagens tridimensionais em tempo real para o exame de ecocardiografia de estresse &#233; evidente quando se analisa as vantagens na captura de imagens e interpreta&#231;&#227;o dos fen&#244;menos isqu&#234;micos e altera&#231;&#245;es da geometria ventricular.</p>
        <p>Peteiro et al. compararam o desempenho da qualidade tridimensional com a da bidimensional para isquemia induzida ao esfor&#231;o,<sup><xref ref-type="bibr" rid="B282">282</xref></sup> bem como Yang et al.,<sup><xref ref-type="bibr" rid="B274">274</xref></sup> que usaram o protocolo com dobutamina. Esses estudos iniciais demonstraram sensibilidade e especificidade semelhantes aos protocolos padr&#245;es com imagem bidimensional, com as vantagens de facilidade e menor tempo de aquisi&#231;&#227;o da imagem.</p>
        <p>Em um estudo com 44 pacientes submetidos a angiografia, Badano et al.<sup><xref ref-type="bibr" rid="B275">275</xref></sup> demonstraram sensibilidade e especificidade da t&#233;cnica tridimensional compar&#225;veis &#224;s da bidimensional em aparelhos com taxas de quadros mais elevadas, bem como a vantagem do m&#233;todo tridimensional para a an&#225;lise de altera&#231;&#245;es apicais relacionadas ao territ&#243;rio da ADA. Os estudiosos apontam a ecocardiografia tridimensional como equivalente &#224; bidimensional, mas com vantagens em alguns aspectos relevantes.</p>
        <p>Usamos a facilidade dos aparelhos tridimensionais na ecocardiografia de estresse.<sup><xref ref-type="bibr" rid="B283">283</xref></sup> A primeira vantagem est&#225; em usar o m&#233;todo de tr&#234;s planos simult&#226;neos, chamado Tri Plano, que oferece os cortes de quatro c&#226;maras apical, duas c&#226;maras apicais e eixo longo apical. Infelizmente, essa modalidade n&#227;o &#233; oferecida por todos os fabricantes de aparelhos tridimensionais. O ajuste do aparelho permite que, ap&#243;s a obten&#231;&#227;o de uma boa janela quatro c&#226;maras, automaticamente se enxergue as outras janelas com boa taxa de quadros, normalmente acima de 30 quadros por segundo, com frequ&#234;ncia alcan&#231;ando 60 quadros por segundo. Obter apenas uma janela para observar o quadro completo pela t&#233;cnica 3D diminui o tempo de obten&#231;&#227;o do clipe para um ter&#231;o, agilizando a execu&#231;&#227;o da ecocardiografia de esfor&#231;o.</p>
        <p>Em exames realizados de acordo com o protocolo de Balke (exerc&#237;cio), &#233; poss&#237;vel capturar imagens a qualquer momento do exerc&#237;cio ou ap&#243;s a interrup&#231;&#227;o, normalmente usando o repouso, baixa carga de esfor&#231;o (eleva&#231;&#227;o de 20% na frequ&#234;ncia de repouso), pico do esfor&#231;o (FC subm&#225;xima ou 85% da FC m&#225;xima prevista para a idade) e recupera&#231;&#227;o. Apenas uma janela apical e focada no corte quatro c&#226;maras perfaz cada est&#225;gio da ecocardiografia de esfor&#231;o e reduz o esfor&#231;o repetido para o membro superior do examinador, que &#233; poupado quando evita-se a rota&#231;&#227;o para obter os dois cortes apicais subsequentes padr&#227;o (<xref ref-type="fig" rid="f33">Figura 25.1</xref>).</p>
        <fig id="f33">
          <label>Figura 25.1</label>
          <caption>
            <title>Janela apical &#250;nica, permitindo a an&#225;lise de todas as paredes do ventr&#237;culo esquerdo, poupando tempo e o esfor&#231;o do examinador.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>O corte <italic>multislice</italic>, que oferece m&#250;ltiplos cortes transversais do ventr&#237;culo, normalmente n&#227;o &#233; envolvido, mas pode ser usado para casos duvidosos em imagem adquirida em 3D previamente. Com a t&#233;cnica <italic>multislice</italic>, &#233; poss&#237;vel "cortar" o VE transversal e milimetricamente e observar a an&#225;lise segmentar de modo mais detalhado e minucioso, comparando a contra&#231;&#227;o do VE em cada etapa da ecocardiografia de esfor&#231;o.</p>
        <p>Alguns servi&#231;os utilizam o protocolo que combina a aquisi&#231;&#227;o bidimensional triplano com imagens tridimensionais em tempo real, usando o protocolo de captura e an&#225;lise do primeiro e analisando imagens do segundo, em separado.<sup><xref ref-type="bibr" rid="B277">277</xref></sup> O m&#233;todo &#233; utilizado tamb&#233;m e principalmente no ensino da t&#233;cnica para iniciantes. Lidando com os dois formatos, o examinador pode escolher a imagem com maior representatividade para as altera&#231;&#245;es provocadas pelo estresse f&#237;sico ou farmacol&#243;gico. Esse processo pode ajudar na adapta&#231;&#227;o ao modo tridimensional, com sua menor taxa de quadros, mas melhor interpreta&#231;&#227;o de altera&#231;&#245;es volum&#233;tricas.</p>
        <p>A obten&#231;&#227;o de imagens tridimensionais precisa de ajuste no aparelho para permitir a obten&#231;&#227;o de melhor taxa de volumes por segundo. Trabalhando com a menor profundidade e abertura poss&#237;veis, &#233; poss&#237;vel obter taxas acima de 24 volumes por segundo. A possibilidade de rota&#231;&#227;o dos eixos do VE para an&#225;lise mais focada no &#225;pice ou na base, bem como o giro para an&#225;lise da contra&#231;&#227;o nas laterais da imagem, permite uma interpreta&#231;&#227;o da contra&#231;&#227;o superior &#224;quela obtida na aquisi&#231;&#227;o convencional (<xref ref-type="fig" rid="f34">Figura 25.2</xref>).</p>
        <fig id="f34">
          <label>Figura 25.2</label>
          <caption>
            <title>Imagem tridimensional &#224; ecocardiografia de estresse.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>Dada a capacidade de adquirir todo o volume do VE em um &#250;nico batimento, a ecocardiografia tridimensional em tempo real oferece uma promessa substancial para se tornar o padr&#227;o de refer&#234;ncia na avalia&#231;&#227;o de pacientes com suspeita de DAC.</p>
        <p>A maior produtividade com menor tempo para o exame e maior conforto para o executor do exame s&#227;o vantagens significativas. A execu&#231;&#227;o e a an&#225;lise do exame tridimensional exigem uma adapta&#231;&#227;o do servi&#231;o.</p>
        <p>Em centros com alto volume de ecocardiografia de estresse, a aquisi&#231;&#227;o de aparelhos capazes de realizar o exame de estresse tridimensional pode ser importante para otimizar a din&#226;mica do servi&#231;o.</p>
      </sec>
    </sec>
    <sec>
      <title>26. A Ecocardiografia de Estresse na Sala de Emerg&#234;ncia: Indica&#231;&#245;es e Aplica&#231;&#245;es</title>
      <p>A dor tor&#225;cica &#233; uma das principais queixas em salas de emerg&#234;ncias hospitalares. Nos EUA, a queixa de dor tor&#225;cica representa 7 milh&#245;es de atendimentos anuais, sendo 30% destes categorizados como SCA. Estima-se que at&#233; 4% dos pacientes s&#227;o liberados da sala de emerg&#234;ncia erroneamente em decorr&#234;ncia de apresenta&#231;&#227;o at&#237;pica ou ECG n&#227;o diagn&#243;stico.<sup><xref ref-type="bibr" rid="B284">284</xref></sup> Em uma &#233;poca de custos crescentes na sa&#250;de, uma interna&#231;&#227;o hospitalar de m&#250;ltiplos dias para "descartar" a SCA n&#227;o &#233; mais sustent&#225;vel, e a condi&#231;&#227;o requer protocolos e fluxos de avalia&#231;&#227;o eficazes.</p>
      <p>Para os pacientes nos extremos do espectro de risco coronariano, a triagem &#233; f&#225;cil, e aqueles com SCA definida s&#227;o encaminhados diretamente para o cateterismo card&#237;aco, enquanto aqueles com probabilidade muito baixa de isquemia coronariana s&#227;o liberados. O maior desafio se concentra nos pacientes com risco card&#237;aco baixo a intermedi&#225;rio e sem evid&#234;ncias claras de diagn&#243;stico de SCA, seja por ECG n&#227;o diagn&#243;stico, seja por enzimas card&#237;acas de fase aguda negativas. Nesse grupo n&#227;o desprez&#237;vel de pacientes, o dilema diagn&#243;stico pode ser caro e, muitas vezes, frustrante.</p>
      <sec>
        <title>26.1. Utilidade da Ecocardiografia de Estresse na Emerg&#234;ncia</title>
        <p>A ecocardiografia na sala de emerg&#234;ncia permite avaliar a fun&#231;&#227;o card&#237;aca em repouso e detectar diagn&#243;sticos diferenciais importantes que causam dor tor&#225;cica aguda, como dissec&#231;&#227;o de aorta e embolia pulmonar, reduzindo sensivelmente o tempo de avalia&#231;&#227;o. A utiliza&#231;&#227;o da modalidade de estresse, tanto farmacol&#243;gico quanto f&#237;sico, dependendo das caracter&#237;sticas do paciente, disponibiliza de forma r&#225;pida e eficaz uma ferramenta importante para estratifica&#231;&#227;o de risco n&#227;o invasiva.</p>
        <p>Uma das principais limita&#231;&#245;es do m&#233;todo &#233; a qualidade das imagens, que pode ser afetada por fatores como obesidade, doen&#231;a pulmonar subjacente ou dificuldades t&#233;cnicas. Para superar essa barreira, como nos casos em que a janela &#233; desfavor&#225;vel e em que mais de dois segmentos n&#227;o s&#227;o visualizados adequadamente, &#233; poss&#237;vel utilizar o ARUS para melhorar a acur&#225;cia do exame.</p>
        <p>Em 2007, foram publicados os resultados do estudo ASSENCE (Avalia&#231;&#227;o de Custo-Efetividade de Diversas Estrat&#233;gias de Diagn&#243;stico Precoce em Pacientes com Dor Tor&#225;cica Aguda e Eletrocardiograma N&#227;o Conclusivo). Trata-se de um ensaio cl&#237;nico randomizado de 10 centros que comparou a rela&#231;&#227;o custo-efetividade da EED e atropina precoce em compara&#231;&#227;o com avalia&#231;&#227;o padr&#227;o e ergometria. Foram inclu&#237;dos pacientes com ECG n&#227;o diagn&#243;stico de SCA, com biomarcadores iniciais negativos para les&#227;o mioc&#225;rdica e capacidade de realizar teste de esfor&#231;o (ergometria). O principal objetivo do estudo foi a rela&#231;&#227;o custo-efetividade, levando em considera&#231;&#227;o o tempo de hospitaliza&#231;&#227;o durante a admiss&#227;o inicial e as hospitaliza&#231;&#245;es repetidas, procedimentos diagn&#243;sticos hospitalares e ambulatoriais e tratamentos. Os desfechos secund&#225;rios inclu&#237;ram frequ&#234;ncia de eventos cardiovasculares adversos maiores (MACE) precoces e tardios, reinterna&#231;&#227;o e revasculariza&#231;&#227;o coronariana. Entre os 110 pacientes no bra&#231;o da ecocardiografia de estresse, 90 (82%) receberam alta direta, em compara&#231;&#227;o com 78 dos 89 (88%) no bra&#231;o do ECG de esfor&#231;o. Para esses pacientes, os custos gerais em 2 meses foram 39% menores no bra&#231;o da ecocardiografia de estresse em compara&#231;&#227;o com o bra&#231;o do teste ergom&#233;trico (US$ 1.029 vs. US$ 1.684; p=0,005). Nos pacientes que necessitaram de interna&#231;&#227;o, os custos n&#227;o diferiram significativamente entre as estrat&#233;gias diagn&#243;sticas. Assim, o estudo ASSENCE confirmou a tend&#234;ncia geral de que a adi&#231;&#227;o de exames de imagem &#224;s estrat&#233;gias de diagn&#243;stico sem imagem dos cuidados padr&#245;es &#233; custo-efetiva. A origem dessa economia foi atribu&#237;da a menos eventos tardios (nenhum no bra&#231;o da ecocardiografia vs. 11% no bra&#231;o da ergometria), incluindo reinterna&#231;&#245;es, SCA e interven&#231;&#227;o percut&#226;nea tardia ap&#243;s ECG de estresse negativo.<sup><xref ref-type="bibr" rid="B285">285</xref></sup></p>
        <p>No mesmo ano, Jeetley et al.<sup><xref ref-type="bibr" rid="B286">286</xref></sup> apresentaram um ensaio cl&#237;nico randomizado de efic&#225;cia cl&#237;nica, de centro &#250;nico, em que 433 pacientes tiveram avalia&#231;&#245;es iniciais negativas para SCA e foram randomizados para ecocardiografia de estresse ou ergometria. O desfecho prim&#225;rio foi a identifica&#231;&#227;o correta dos pacientes que apresentavam alto risco de um desfecho combinado de morte card&#237;aca, infarto do mioc&#225;rdio n&#227;o fatal ou revasculariza&#231;&#227;o coronariana. O desfecho secund&#225;rio foi o custo para o diagn&#243;stico. O risco pr&#233;-teste foi classificado de acordo com o escore de risco TIMI (<italic>Thrombolysis In Myocardial Infarction</italic>). O risco p&#243;s-teste foi considerado baixo se os resultados do teste eram negativos e alto se eram positivos, independentemente do risco pr&#233;-teste. Um n&#250;mero significativamente maior de pacientes com ecocardiografia de estresse do que pacientes com ergometria foram classificados como de baixo risco p&#243;s-teste e, portanto, eleg&#237;veis para alta imediata (77% vs. 33%; p &lt; 0,001). Al&#233;m disso, um ecocardiograma de estresse positivo para alto risco foi mais preciso do que a ergometria na previs&#227;o desse desfecho prim&#225;rio (51% vs. 29%; p = 0,01). A taxa de coronariografias normais no grupo de ergometria positiva foi quase duas vezes maior que no grupo de ecocardiografia de estresse (39% vs. 23%). Significativamente mais pacientes com ergometria do que pacientes com ecocardiografia de estresse necessitaram de mais testes diagn&#243;sticos durante o per&#237;odo de acompanhamento (47% vs. 20%; p &lt; 0,001). O custo m&#233;dio para o diagn&#243;stico foi significativamente menor no grupo da ecocardiografia de estresse do que no grupo da ergometria (&#163; 326 vs. &#163; 495; p = 0,01), evidenciando os "benef&#237;cios cl&#237;nicos e de custo-efetividade" significativos da ecocardiografia de estresse em rela&#231;&#227;o &#224; ergometria em pacientes com suspeita de SCA.<sup><xref ref-type="bibr" rid="B286">286</xref></sup></p>
        <p>Em 2021, uma for&#231;a-tarefa liderada pela AHA, ACC e ASE publicou uma diretriz de avalia&#231;&#227;o e diagn&#243;stico de dor tor&#225;cica, na qual se estabeleceu que pacientes com dor tor&#225;cica aguda e de baixo risco n&#227;o necessitam de exames adicionais de imagem anat&#244;micos ou funcionais e podem ser liberados para avalia&#231;&#227;o ambulatorial.<sup><xref ref-type="bibr" rid="B287">287</xref></sup> A ecocardiografia transtor&#225;cica (ETT), como foi comentado, pode visualizar e auxiliar no diagn&#243;stico diferencial entre as in&#250;meras causas de dor tor&#225;cica aguda, como dissec&#231;&#227;o a&#243;rtica aguda, derrame peric&#225;rdico, cardiomiopatia de estresse ou catecolin&#233;rgica (s&#237;ndrome de Takotsubo) e CMH, entre outras. A visualiza&#231;&#227;o da fun&#231;&#227;o ventricular esquerda e direita e as anormalidades da contratilidade segmentar permitem a avalia&#231;&#227;o do risco de DAC e podem ajudar na decis&#227;o cl&#237;nica. Ap&#243;s a exclus&#227;o de SCA, em pacientes de risco intermedi&#225;rio, a ecocardiografia de estresse pode ser utilizada para definir a presen&#231;a e a gravidade da cardiopatia isqu&#234;mica e para fins de estratifica&#231;&#227;o de risco. Tamb&#233;m para pacientes de risco intermedi&#225;rio, com angiotomografia inconclusiva, a ecocardiografia de estresse pode ser uma alternativa diagn&#243;stica.<sup><xref ref-type="bibr" rid="B287">287</xref></sup></p>
        <p>Mais recentemente, em 2023, foram publicadas as diretrizes para manejo da SCA da Sociedade Europeia de Cardiologia. Nelas, a ecocardiografia de estresse tamb&#233;m foi colocada como ferramenta importante para a triagem em pacientes sem eleva&#231;&#227;o ou com eleva&#231;&#227;o incerta de biomarcadores e ECG n&#227;o diagn&#243;stico, com n&#237;vel de evid&#234;ncia A e indica&#231;&#227;o classe IIA<sup><xref ref-type="bibr" rid="B288">288</xref></sup> (<xref ref-type="fig" rid="f35">Figura 26.1</xref>).</p>
        <fig id="f35">
          <label>Figura 26.1</label>
          <caption>
            <title>Organograma adaptado da diretriz de manejo de s&#237;ndrome coronariana aguda da Sociedade Europeia de Cardiologia (2023).<sup><xref ref-type="bibr" rid="B288">288</xref></sup></title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>Assim, a ecocardiografia de estresse na sala de emerg&#234;ncia &#233; uma ferramenta valiosa no diagn&#243;stico e manejo de pacientes com suspeita de SCA, principalmente naqueles com risco intermedi&#225;rio, sem ECG diagn&#243;stico e sem altera&#231;&#245;es enzim&#225;ticas. No entanto, &#233; importante considerar suas limita&#231;&#245;es e garantir que os m&#233;dicos estejam treinados na t&#233;cnica. Importante tamb&#233;m &#233; que a log&#237;stica do servi&#231;o esteja preparada para realizar o exame em curto espa&#231;o de tempo, preferencialmente nas primeiras 24 horas, garantido a custo-efetividade do m&#233;todo conforme observado nos diferentes ensaios cl&#237;nicos.</p>
      </sec>
    </sec>
    <sec>
      <title>27. Ecocardiografia de Estresse no P&#243;s-Transplante Card&#237;aco</title>
      <p>A ecocardiografia de estresse &#233; uma t&#233;cnica diagn&#243;stica que revela isquemia mioc&#225;rdica induz&#237;vel em pacientes transplantados card&#237;acos. O desenvolvimento de doen&#231;a coronariana ateroscler&#243;tica, conhecida como vasculopatia do enxerto, &#233; a principal causa de fal&#234;ncia do enxerto e morte durante o primeiro ano de transplante card&#237;aco.</p>
      <p>A angiografia coron&#225;ria por cateterismo card&#237;aco tem sido, ao longo dos anos, usada rotineiramente para avaliar a DAC do enxerto, mas &#233; um procedimento invasivo e apresenta maior risco de morbidade em pacientes transplantados card&#237;acos.</p>
      <p>A ecocardiografia de estresse &#233; capaz de identificar doen&#231;a vascular do enxerto e tem valor progn&#243;stico reconhecido na &#225;rea. Assim, um ecocardiograma de estresse normal, sem altera&#231;&#245;es na contratilidade segmentar, justifica o adiamento de estudos invasivos.<sup><xref ref-type="bibr" rid="B289">289</xref></sup></p>
      <p>Durante um estudo, devido &#224; denerva&#231;&#227;o cir&#250;rgica do transplante card&#237;aco, alguns pacientes atingiram sua FC ideal com baixas doses de dobutamina. Isso ocorre porque os pacientes transplantados card&#237;acos apresentam resposta cronotr&#243;pica aumentada &#224; estimula&#231;&#227;o beta-adren&#233;rgica com esse medicamento. Em outros casos, &#233; necess&#225;ria a adi&#231;&#227;o de atropina, apesar da dose m&#225;xima de dobutamina, o que em geral acontece em casos de receptores idosos.<sup><xref ref-type="bibr" rid="B290">290</xref></sup></p>
      <p>A dobutamina &#233; o agente estressor mais utilizado, com sensibilidade entre 70 e 80% para a detec&#231;&#227;o de vasculopatia do enxerto.<sup><xref ref-type="bibr" rid="B291">291</xref></sup> Devido &#224; baixa resposta da FC ao exerc&#237;cio causada pelo estado de desnerva&#231;&#227;o, os protocolos de exerc&#237;cio apresentam uma sensibilidade muito limitada, de 15 a 33%.<sup><xref ref-type="bibr" rid="B292">292</xref></sup></p>
      <p>Um estudo de Bacal et al.<sup><xref ref-type="bibr" rid="B293">293</xref></sup> com ecocardiografia de estresse positivo mostrou que este foi um preditor independente de eventos card&#237;acos e/ou morte em um seguimento de 4 anos. Por outro lado, um ecocardiograma de estresse negativo com dobutamina indicou baixo risco para doen&#231;a do enxerto coronariano e baixa taxa de incid&#234;ncia de efeitos card&#237;acos adversos.<sup><xref ref-type="bibr" rid="B294">294</xref></sup></p>
      <p>A EED &#233; a modalidade mais recomendada para vigil&#226;ncia rotineira da vasculopatia do enxerto durante os primeiros 5 anos ap&#243;s o transplante card&#237;aco devido &#224; alta preval&#234;ncia da doen&#231;a no p&#243;s-transplante card&#237;aco.<sup><xref ref-type="bibr" rid="B295">295</xref></sup></p>
    </sec>
    <sec>
      <title>28. Ecocardiografia de Estresse em Subgrupos Especiais (Bloqueio de Ramo Esquerdo, Bloqueio do Ramo Direito e Fibrila&#231;&#227;o Atrial)</title>
      <sec>
        <title>28.1. Bloqueio de Ramo Esquerdo</title>
        <p>O BRE &#233; uma condi&#231;&#227;o frequente, de etiologia variada e desafiadora do ponto de vista diagn&#243;stico. O BRE afeta a contra&#231;&#227;o mioc&#225;rdica, o enchimento diast&#243;lico do VE e a perfus&#227;o coronariana em graus vari&#225;veis de acordo com gravidade do bloqueio e da patologia card&#237;aca subadjacente.<sup><xref ref-type="bibr" rid="B296">296</xref></sup></p>
        <p>Aproximadamente 2% dos pacientes encaminhados para teste ergom&#233;trico apresentam BRE fixo ou intermitente.<sup><xref ref-type="bibr" rid="B297">297</xref></sup> A preval&#234;ncia de DAC em pacientes com BRE varia entre 30 e 50%.<sup><xref ref-type="bibr" rid="B298">298</xref></sup> Na presen&#231;a de BRE, o ECG n&#227;o &#233; interpret&#225;vel para avalia&#231;&#227;o de isquemia, sendo necess&#225;rio a realiza&#231;&#227;o de uma t&#233;cnica de imagem para a investiga&#231;&#227;o n&#227;o invasiva de DAC.</p>
        <p>A ativa&#231;&#227;o el&#233;trica alterada interfere no movimento da parede septal, que pode variar desde um movimento normal at&#233; um movimento paradoxal. Na presen&#231;a de um complexo QRS com dura&#231;&#227;o &lt; 150 ms, frequentemente o espessamento parietal &#233; normal e a capacidade de contra&#231;&#227;o est&#225; preservada. J&#225; o padr&#227;o de movimenta&#231;&#227;o paradoxal da parede septal &#233; encontrado com mais frequ&#234;ncia quando a dura&#231;&#227;o do complexo QRS ultrapassa os 150 ms e/ou na presen&#231;a de fibrose septal.</p>
        <p>Apesar da maior dificuldade na interpreta&#231;&#227;o da motilidade septal devido ao movimento anormal da parede, a ecocardiografia de estresse &#233; a melhor op&#231;&#227;o para o diagn&#243;stico de DAC nesse cen&#225;rio.<sup><xref ref-type="bibr" rid="B44">44</xref>,<xref ref-type="bibr" rid="B298">298</xref></sup> &#201; uma modalidade mais espec&#237;fica do que a cintilografia do mioc&#225;rdio,<sup><xref ref-type="bibr" rid="B44">44</xref>,<xref ref-type="bibr" rid="B299">299</xref></sup> com boa sensibilidade nesses casos, embora essa sensibilidade seja menor para avalia&#231;&#227;o do territ&#243;rio da ADA esquerda na presen&#231;a de discinesia/dissincronia septal vista &#224; ecocardiografia basal.<sup><xref ref-type="bibr" rid="B298">298</xref></sup></p>
        <p>O valor progn&#243;stico da ecocardiografia de estresse nos pacientes com BRE &#233; excelente, especialmente em pacientes sem infarto do mioc&#225;rdio pr&#233;vio. Cortigiani et al. avaliaram o valor preditivo progn&#243;stico da ecocardiografia de estresse farmacol&#243;gico em pacientes com BRE. Nesse estudo, duas vari&#225;veis ecocardiogr&#225;ficas estavam associadas a um risco elevado de morte por causa card&#237;aca: o WMSI em repouso e a varia&#231;&#227;o do WMSI no pico do estresse. A sobrevida em cinco anos foi de 77% no grupo de pacientes com teste positivo para isquemia mioc&#225;rdica e de 92% no grupo com teste normal (p = 0,02).<sup><xref ref-type="bibr" rid="B300">300</xref></sup></p>
        <p>O valor diagn&#243;stico e progn&#243;stico da ecocardiografia de estresse pode ser melhorado pela adi&#231;&#227;o da avalia&#231;&#227;o simult&#226;nea da reserva de velocidade do fluxo coronariano na ADA esquerda<sup><xref ref-type="bibr" rid="B301">301</xref></sup> ou da perfus&#227;o mioc&#225;rdica com ARUS.<sup><xref ref-type="bibr" rid="B302">302</xref></sup></p>
      </sec>
      <sec>
        <title>28.2. Bloqueio do Ramo Direito</title>
        <p>O bloqueio do ramo direito (BRD) &#233; encontrado com frequ&#234;ncia na popula&#231;&#227;o geral saud&#225;vel, mas pode ser causado por condi&#231;&#245;es que afetam o ramo direito do feixe de condu&#231;&#227;o. As causas poss&#237;veis incluem trauma, altera&#231;&#245;es estruturais, doen&#231;as infiltrativas e infecciosas, miocardite e DAC.</p>
        <p>O BRD est&#225; presente em aproximadamente 2% a 3% dos pacientes com DAC.<sup><xref ref-type="bibr" rid="B296">296</xref>,<xref ref-type="bibr" rid="B297">297</xref></sup> Nesse cen&#225;rio, sua presen&#231;a &#233; um preditor independente de mortalidade por qualquer causa.<sup><xref ref-type="bibr" rid="B303">303</xref></sup> Em especial, a ocorr&#234;ncia de BRD no contexto da SCA est&#225; significativamente associada com o aumento na mortalidade intra-hospitalar, mesmo ap&#243;s interven&#231;&#227;o coronariana percut&#226;nea prim&#225;ria.<sup><xref ref-type="bibr" rid="B304">304</xref></sup> A ecocardiografia de estresse &#233; uma excelente modalidade diagn&#243;stica para a investiga&#231;&#227;o de DAC, uma vez que o BRD normalmente n&#227;o afeta o movimento regional da parede. Al&#233;m disso, ela fornece uma estratifica&#231;&#227;o progn&#243;stica eficiente e aditiva aos par&#226;metros simples da eletrocardiografia em repouso, como o bloqueio fascicular anterior esquerdo. Em pacientes com suspeita de DAC submetidos a ecocardiografia de estresse, o BRD associado ao bloqueio divisional anterossuperior do ramo esquerdo se mostrou um preditor independente de mortalidade.<sup><xref ref-type="bibr" rid="B305">305</xref></sup></p>
      </sec>
      <sec>
        <title>28.3. Fibrila&#231;&#227;o Atrial</title>
        <p>A preval&#234;ncia de FA &#233; muito baixa entre os jovens (&lt; 1% em pessoas com menos de 40 anos), mas aumenta com a idade, atingindo at&#233; 17% dos indiv&#237;duos com mais de 80 anos.<sup><xref ref-type="bibr" rid="B306">306</xref></sup> A DAC &#233; uma das condi&#231;&#245;es cardiovasculares mais comumente associadas &#224; FA.</p>
        <p>O encurtamento da fase diast&#243;lica na FA pode gerar resultados falso-positivos durante o teste ergom&#233;trico, uma vez que a perfus&#227;o subendoc&#225;rdica est&#225; comprometida. Nesse contexto, a ecocardiografia de estresse &#233; uma modalidade eficaz. Em geral, o estresse com vasodilatadores &#233; melhor tolerado do que o estresse com dobutamina. Entretanto, apesar da resposta cronotr&#243;pica aumentada &#224; infus&#227;o de dobutamina em pacientes com FA comparados aos pacientes em ritmo sinusal, a EED apresenta bom valor diagn&#243;stico nesses pacientes. Hobday et al.<sup><xref ref-type="bibr" rid="B307">307</xref></sup> demonstraram que um percentual maior dos pacientes com FA atingiram a FC alvo e precisaram de menor dose de atropina em compara&#231;&#227;o com os pacientes em ritmo sinusal. Nesse mesmo estudo, resultados positivos para isquemia mioc&#225;rdica ocorreram de forma semelhante entre os pacientes com FA e ritmo sinusal, e a utiliza&#231;&#227;o de betabloqueadores foi similar.<sup><xref ref-type="bibr" rid="B307">307</xref></sup> A atropina, por outro lado, deve ser usada com parcim&#244;nia em pacientes portadores de FA, pelo risco de elevar demais a FC, ocasionando risco de interna&#231;&#227;o hospitalar.</p>
        <p>O aparecimento de FA durante a ecocardiografia de estresse &#233; uma complica&#231;&#227;o mais comum em pacientes com substrato arritmog&#234;nico, quando o agente estressor utilizado &#233; a dobutamina. Em uma revis&#227;o publicada com base em 26 estudos sobre as complica&#231;&#245;es associadas &#224; EED, a incid&#234;ncia de FA foi de 0,9%.<sup><xref ref-type="bibr" rid="B308">308</xref></sup> Em um estudo recente que avaliou retrospectivamente 4.917 pacientes consecutivos submetidos a EED, foram identificados como principais fatores relacionados ao desenvolvimento de FA durante o exame, a hist&#243;ria pr&#233;via de FA parox&#237;stica (p = 0,02) e a idade avan&#231;ada, com incid&#234;ncia de 4% nos pacientes com mais de 80 anos (p &lt; 0,0001).<sup><xref ref-type="bibr" rid="B309">309</xref></sup> Na maioria dos pacientes, o retorno para o ritmo sinusal ocorre durante a primeira hora ap&#243;s o in&#237;cio da arritmia,<sup><xref ref-type="bibr" rid="B310">310</xref></sup> geralmente sendo necess&#225;rio a administra&#231;&#227;o de betabloqueador tipo metoprolol.</p>
      </sec>
    </sec>
    <sec>
      <title>29. Ecocardiografia de Estresse no Pr&#233;-Operat&#243;rio de Cirurgia Vascular, em Mulheres e Idosos</title>
      <sec>
        <title>29.1. Pr&#233;-Operat&#243;rio de Cirurgia Vascular</title>
        <p>Pacientes submetidos a cirurgias vasculares apresentam risco elevado de eventos cardiovasculares durante o perioperat&#243;rio. Al&#233;m das caracter&#237;sticas cl&#237;nicas dos pacientes, isso tamb&#233;m pode ser atribu&#237;do &#224; coexist&#234;ncia da DAC.<sup><xref ref-type="bibr" rid="B311">311</xref>,<xref ref-type="bibr" rid="B312">312</xref></sup> Al&#233;m disso, a natureza e a complexidade das interven&#231;&#245;es vasculares desempenham papel relevante nesse cen&#225;rio.<sup><xref ref-type="bibr" rid="B313">313</xref></sup></p>
        <p>Assim, a estratifica&#231;&#227;o pr&#233;-operat&#243;ria &#233; de extrema import&#226;ncia e tem como objetivo identificar pacientes mais suscet&#237;veis a eventos cardiovasculares, possibilitando implementa&#231;&#227;o de medidas que reduzir&#227;o a morbimortalidade. Nesse contexto, a ecocardiografia de estresse (f&#237;sico ou farmacol&#243;gico) se destaca como um m&#233;todo n&#227;o invasivo, amplamente dispon&#237;vel e de baixo custo.</p>
        <p>A EEF oferece benef&#237;cios na avalia&#231;&#227;o da capacidade funcional e na resposta hemodin&#226;mica ao esfor&#231;o. No entanto, a presen&#231;a de doen&#231;a vascular perif&#233;rica e a baixa capacidade funcional podem impossibilitar a efic&#225;cia do teste, sendo, portanto, recomendado o estresse farmacol&#243;gico com dobutamina ou dipiridamol nesse subgrupo de pacientes. A escolha do agente farmacol&#243;gico deve ser pautada pela disponibilidade, experi&#234;ncia de cada centro, mecanismo de a&#231;&#227;o dos medicamentos e doen&#231;as vasculares preexistentes.</p>
        <p>A EED tem se mostrado &#250;til e segura, podendo ser empregada inclusive em pacientes com aneurisma de aorta abdominal.<sup><xref ref-type="bibr" rid="B314">314</xref></sup> O teste com agentes vasodilatadores (adenosina ou dipiridamol) tamb&#233;m pode ser considerado uma alternativa vi&#225;vel e com boa acur&#225;cia,<sup><xref ref-type="bibr" rid="B312">312</xref></sup> cabendo ressaltar que o seu uso &#233; contraindicado na presen&#231;a de doen&#231;a carot&#237;dea grave bilateral.<sup><xref ref-type="bibr" rid="B313">313</xref></sup></p>
        <p>Pacientes que apresentam ecocardiograma de estresse positivo t&#234;m maior incid&#234;ncia de eventos cardiovasculares. Os exames sob estresse farmacol&#243;gico demonstram excelente valor preditivo negativo, variando entre 90 e 100%, enquanto o valor preditivo positivo &#233; mais baixo, entre 25 e 45%.<sup><xref ref-type="bibr" rid="B312">312</xref></sup> Os fatores preditores mais significativos de eventos adversos no p&#243;s-operat&#243;rio s&#227;o a presen&#231;a de isquemia e hist&#243;ria de insufici&#234;ncia card&#237;aca congestiva. Na EED, a FC na qual a isquemia se desenvolve pode ser utilizada para estratificar os pacientes em risco baixo, intermedi&#225;rio e alto para infarto e &#243;bito no p&#243;s-operat&#243;rio.<sup><xref ref-type="bibr" rid="B315">315</xref>,<xref ref-type="bibr" rid="B316">316</xref></sup></p>
        <p>A ocorr&#234;ncia de novas altera&#231;&#245;es da motilidade parietal induzidas pelo estresse, extensa (tr&#234;s ou mais segmentos) ou limitada (um ou dois segmentos), associada com hist&#243;ria de infarto pr&#233;vio, tem sido caracterizada como fatores independentes para a ocorr&#234;ncia de eventos card&#237;acos tardios.<sup><xref ref-type="bibr" rid="B317">317</xref></sup></p>
        <p>Em uma meta-an&#225;lise que englobou seis testes n&#227;o invasivos na avalia&#231;&#227;o pr&#233;-operat&#243;ria de cirurgias vasculares, os testes de estresse farmacol&#243;gico apresentaram sensibilidade e especificidade global mais elevadas, sendo que a EED demonstrou tend&#234;ncia para desempenho diagn&#243;stico superior aos outros exames.<sup><xref ref-type="bibr" rid="B318">318</xref></sup></p>
        <p>Em m&#250;ltiplos estudos e meta-an&#225;lises, o valor progn&#243;stico da EED foi, no m&#237;nimo, t&#227;o eficaz quanto o da cintilografia do mioc&#225;rdio em prever a ocorr&#234;ncia de eventos adversos no p&#243;s-operat&#243;rio.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B311">311</xref>,<xref ref-type="bibr" rid="B319">319</xref></sup></p>
      </sec>
      <sec>
        <title>29.2. Mulheres</title>
        <p>A doen&#231;a cardiovascular (DCV) &#233; a principal causa de morte em mulheres em todo o mundo. O diagn&#243;stico e o manejo apropriados permanecem um desafio, uma vez que pacientes do sexo feminino podem apresentar sintomas at&#237;picos e, portanto, receber tratamento inadequado.<sup><xref ref-type="bibr" rid="B320">320</xref></sup></p>
        <p>In&#250;meros relatos mostram que as mulheres t&#234;m maior probabilidade de desenvolver angina pectoris como primeiro sintoma de DAC (47% vs. 32%) e s&#227;o menos propensas a apresentar infarto agudo do mioc&#225;rdio (6% vs. 10%) em compara&#231;&#227;o com os homens.<sup><xref ref-type="bibr" rid="B321">321</xref></sup></p>
        <p>A ecocardiografia de estresse &#233; uma ferramenta bem estabelecida e de grande utilidade na investiga&#231;&#227;o diagn&#243;stica de mulheres com suspeita de DAC, bem como de estratifica&#231;&#227;o de risco daquelas com a doen&#231;a diagnosticada. Ela demonstra sensibilidade, especificidade e valor progn&#243;stico sem diferen&#231;as espec&#237;ficas entre os sexos.<sup><xref ref-type="bibr" rid="B322">322</xref></sup> Al&#233;m disso, a acur&#225;cia diagn&#243;stica da EED tem se mostrado similar tanto entre mulheres com dor at&#237;pica quanto em casos angina.<sup><xref ref-type="bibr" rid="B323">323</xref>,<xref ref-type="bibr" rid="B234">234</xref></sup></p>
        <p>Em estudo realizado por Biagini et al.,<sup><xref ref-type="bibr" rid="B325">325</xref></sup> foram inclu&#237;dos 2.276 homens e 1.105 mulheres com DAC suspeita ou conhecida. Eles foram submetidos a EED e a estratifica&#231;&#227;o de risco foi feita ap&#243;s seguimento de 7 anos, observando-se os desfechos de infarto do mioc&#225;rdio n&#227;o fatal e morte cardiovascular. Os resultados mostraram que a EED fornece informa&#231;&#245;es progn&#243;sticas independentes tanto em homens quanto em mulheres.</p>
        <p>Do ponto de vista t&#233;cnico, &#233; importante destacar que as mulheres apresentam maior incid&#234;ncia de hipotens&#227;o arterial durante a EED. Cavidades ventriculares pequenas com maior grau de hipertrofia relativa podem facilitar o surgimento de obstru&#231;&#227;o din&#226;mica na VSVE, levando &#224; hipotens&#227;o e &#224; interrup&#231;&#227;o prematura do teste. Al&#233;m disso, em cora&#231;&#245;es menores, h&#225; maior probabilidade de oblitera&#231;&#227;o da cavidade ventricular esquerda, o que pode mascarar altera&#231;&#245;es sutis na motilidade parietal.<sup><xref ref-type="bibr" rid="B326">326</xref></sup> Tamb&#233;m pode ocorrer dor tor&#225;cica na vig&#234;ncia de obstru&#231;&#227;o din&#226;mica da VSVE, gerando d&#250;vidas sobre a presen&#231;a de isquemia mioc&#225;rdica. O protocolo &#233; o mesmo, mas nesses casos &#233; importante avaliar n&#227;o somente a contratilidade parietal, mas tamb&#233;m a presen&#231;a de gradiente intraventricular,<sup><xref ref-type="bibr" rid="B327">327</xref></sup> uma vez que fatores anat&#244;micos e hemodin&#226;micos card&#237;acos est&#227;o mais presentes nesse subgrupo de pacientes.</p>
        <p>Em resumo, a ecocardiografia de estresse desempenha um papel de grande import&#226;ncia no diagn&#243;stico e progn&#243;stico da DAC nas mulheres.</p>
      </sec>
      <sec>
        <title>29.3. Idosos</title>
        <p>A popula&#231;&#227;o de pacientes com suspeita de DAC com mais de 65 anos &#233; especialmente vulner&#225;vel e est&#225; em constante crescimento. A busca pela abordagem diagn&#243;stica mais eficaz deve ser constante a fim de garantir o tratamento ideal e os melhores desfechos.</p>
        <p>A ecocardiografia de estresse f&#237;sico ou farmacol&#243;gico surge como ferramenta diagn&#243;stica fundamental, combinando os benef&#237;cios da imagem card&#237;aca com a an&#225;lise da fun&#231;&#227;o cardiovascular sob estresse.</p>
        <p>Em pacientes com mais de 65 anos, as informa&#231;&#245;es provenientes da ecocardiografia de estresse (especialmente a resposta do volume sist&#243;lico final do VE e a FE durante o exerc&#237;cio), quando incorporadas aos crit&#233;rios cl&#237;nicos, aos dados do eletrocardiograma e ao ecocardiograma em repouso, aprimoram a capacidade de prever eventos card&#237;acos e a mortalidade por todas as causas.</p>
        <p>Em um estudo com 2.632 idosos (56% homens) capazes de se exercitar, a EEF permitiu valor progn&#243;stico adicional em rela&#231;&#227;o &#224;s vari&#225;veis cl&#237;nicas (idade, diabetes, infarto pr&#233;vio e teste ergom&#233;trico). No esfor&#231;o f&#237;sico, a carga de exerc&#237;cio foi o melhor preditor de eventos card&#237;acos e morte.<sup><xref ref-type="bibr" rid="B327">327</xref></sup></p>
        <p>Diante da incapacidade de se exercitar devido &#224;s particularidades dessa faixa et&#225;ria, a EED tem sido apontada como alternativa vi&#225;vel. Biagini et al.<sup><xref ref-type="bibr" rid="B329">329</xref></sup> estudaram 1.434 pacientes com idade &gt; 65 anos (m&#233;dia 72 &#177; 3 anos) submetidos a EED para avalia&#231;&#227;o de DAC. A presen&#231;a de anormalidades na motilidade parietal foi considerada preditor independente de todas as causas de mortalidade e de desfechos adversos, enquanto o exame normal estava correlacionado com baixa incid&#234;ncia de eventos card&#237;acos. Cortigiani et al.<sup><xref ref-type="bibr" rid="B330">330</xref></sup> demonstraram que a taxa de eventos nos octogen&#225;rios foi 4,5 vezes maior do que nos idosos entre 65 e 69 anos.</p>
        <p>A seguran&#231;a e a acur&#225;cia conferem &#224; ecocardiografia de estresse um papel crucial na avalia&#231;&#227;o diagn&#243;stica e progn&#243;stica de pacientes idosos, contribuindo para o manejo adequado desses indiv&#237;duos.</p>
      </sec>
    </sec>
    <sec>
      <title>30. Ecocardiografia de Estresse na Pediatria: Indica&#231;&#245;es e Protocolos</title>
      <p>Enquanto a ecocardiografia de estresse &#233; uma t&#233;cnica bem estabelecida na cardiologia para pacientes adultos, a baixa preval&#234;ncia de patologias como DAC, doen&#231;as valvares e cardiomiopatia nas crian&#231;as causa uma escassez de dados publicados sobre essa modalidade e sua impopularidade de uso em pediatria. Assim, a ecocardiografia de estresse ainda n&#227;o &#233; t&#227;o utilizada em pacientes pedi&#225;tricos quanto em pacientes adultos devido &#224;s dificuldades inerentes &#224; realiza&#231;&#227;o do exame. Poucos centros utilizam essa modalidade em pacientes pedi&#225;tricos e h&#225; poucas publica&#231;&#245;es na literatura.</p>
      <p>A utiliza&#231;&#227;o do estresse amplia a avalia&#231;&#227;o ecocardiogr&#225;fica, fornecendo dados em um ambiente fisiol&#243;gico que se assemelha mais ao estado tipicamente ativo dessa faixa et&#225;ria.<sup><xref ref-type="bibr" rid="B331">331</xref></sup></p>
      <p>Assim como na popula&#231;&#227;o adulta, as duas quest&#245;es fundamentais que se busca responder s&#227;o: 1) h&#225; isquemia mioc&#225;rdica induz&#237;vel? 2) h&#225; altera&#231;&#245;es hemodin&#226;micas significativas?<sup><xref ref-type="bibr" rid="B332">332</xref></sup></p>
      <p>Como nos adultos, o tipo de estresse pode ser f&#237;sico, na esteira, na bicicleta e ciclomaca, ou farmacol&#243;gico, com dobutamina e, eventualmente, dipiridamol.</p>
      <p>A EEF &#233; bem tolerada em crian&#231;as, pois n&#227;o requer acesso venoso nem seda&#231;&#227;o, por&#233;m s&#243; pode ser realizada em crian&#231;as acima de 6-7 anos que s&#227;o capazes de realizar o exerc&#237;cio e t&#234;m estatura suficiente para caminhar na esteira ou pedalar na bicicleta ou ciclomaca.<sup><xref ref-type="bibr" rid="B332">332</xref>-<xref ref-type="bibr" rid="B335">335</xref></sup> Em geral, utiliza-se o protocolo de Bruce modificado nas duas modalidades.<sup><xref ref-type="bibr" rid="B332">332</xref>-<xref ref-type="bibr" rid="B335">335</xref></sup> O protocolo de James tamb&#233;m pode ser utilizado na bicicleta/ciclomaca.<sup><xref ref-type="bibr" rid="B333">333</xref></sup> J&#225; a EED n&#227;o tem limita&#231;&#227;o de idade; por&#233;m, em crian&#231;as menores de 8 anos, &#233; necess&#225;rio seda&#231;&#227;o profunda e/ou anestesia geral, e em crian&#231;as maiores pode ser necess&#225;rio seda&#231;&#227;o consciente.<sup><xref ref-type="bibr" rid="B333">333</xref></sup> Os protocolos utilizados s&#227;o semelhantes aos usados com adultos.<sup><xref ref-type="bibr" rid="B333">333</xref>-<xref ref-type="bibr" rid="B336">336</xref></sup> Geralmente, a infus&#227;o de dobutamina come&#231;a com 5 mcg/kg/min e &#233; aumentada em intervalos de 3 minutos para 10, 20, 30, 40, podendo chegar a 50 mcg/kg/min. Se a FC m&#225;xima alvo (85% da FC m&#225;xima para a idade) n&#227;o for atingida para a obten&#231;&#227;o de um teste conclusivo, uma dose baixa de atropina (0,01 mg/kg) &#233; administrada na dose m&#225;xima de dobutamina. Contudo, a FC a ser atingida nessa popula&#231;&#227;o &#233; muito alta.</p>
      <p>Uma alternativa &#233; usar doses baixas ou moderadas (entre 5 e 20 mcg/kg/min) em infus&#227;o cont&#237;nua de dobutamina para avaliar a reserva contr&#225;til card&#237;aca.<sup><xref ref-type="bibr" rid="B333">333</xref>,<xref ref-type="bibr" rid="B337">337</xref></sup> A dose padr&#227;o do dipiridamol &#233; de 0,84 mg/kg, conforme o padr&#227;o adulto j&#225; mencionado.</p>
      <p>Os efeitos colaterais s&#227;o semelhantes aos observados em pacientes adultos.<sup><xref ref-type="bibr" rid="B333">333</xref>-<xref ref-type="bibr" rid="B336">336</xref></sup> Complica&#231;&#245;es como arritmias ventriculares sustentadas s&#227;o raras, mas n&#227;o h&#225; dados suficientes sobre essas complica&#231;&#245;es em pacientes pedi&#225;tricos na literatura.<sup><xref ref-type="bibr" rid="B333">333</xref></sup></p>
      <p>As principais indica&#231;&#245;es para realiza&#231;&#227;o de ecocardiografia de estresse em pediatria s&#227;o: avalia&#231;&#227;o de isquemia mioc&#225;rdica, detec&#231;&#227;o precoce de disfun&#231;&#227;o mioc&#225;rdica, avalia&#231;&#227;o din&#226;mica de gradientes na CMH, avalia&#231;&#227;o da fun&#231;&#227;o do ventr&#237;culo direito e avalia&#231;&#227;o para a realiza&#231;&#227;o de atividades f&#237;sicas nos pacientes com cardiopatias cong&#234;nitas,<sup><xref ref-type="bibr" rid="B332">332</xref></sup> al&#233;m do exame tamb&#233;m ter aplica&#231;&#227;o cl&#237;nica no p&#243;s-transplante card&#237;aco e p&#243;s-quimioterapia.<sup><xref ref-type="bibr" rid="B333">333</xref>,<xref ref-type="bibr" rid="B338">338</xref></sup></p>
      <p>As <xref ref-type="table" rid="t23">Tabelas 30.1</xref> e <xref ref-type="table" rid="t24">30.2</xref> apresentam as indica&#231;&#245;es, com um resumo dos artigos mais recentes.</p>
      <table-wrap id="t23">
        <label>Tabela 30.1</label>
        <caption>
          <title>Indica&#231;&#245;es e tipos de ecocardiografia de estresse em crian&#231;as, adolescentes e adultos jovens</title>
        </caption>
        <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 style="background-color:#76B4CF">
              <th align="left" valign="middle">Indica&#231;&#227;o</th>
              <th align="center" valign="middle">N&#186; Pcts</th>
              <th align="center" valign="middle">Idade</th>
              <th align="center" valign="middle">Tipo de estresse</th>
              <th align="center" valign="middle">Achados</th>
            </tr>
          </thead>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr>
              <td align="left" valign="middle">
                <bold>Doen&#231;a de Kawasaki</bold>
              </td>
              <td align="center" valign="middle"/>
              <td align="center" valign="middle"/>
              <td align="center" valign="middle"/>
              <td align="center" valign="middle"/>
            </tr>
            <tr>
              <td align="left" valign="middle">Pahl et al. (1995)<sup><xref ref-type="bibr" rid="B335">335</xref></sup></td>
              <td align="center" valign="middle">28</td>
              <td align="center" valign="middle">10,7 anos (mediana)</td>
              <td align="center" valign="middle">EEF/esteira</td>
              <td align="center" valign="middle">EEF detectou altera&#231;&#227;o da contratilidade segmentar, sendo superior &#224; avalia&#231;&#227;o da eletrocardiografia isolada</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Noto et al. (1996)<sup><xref ref-type="bibr" rid="B336">336</xref></sup></td>
              <td align="center" valign="middle">50</td>
              <td align="center" valign="middle">13,6 anos (m&#233;dia)</td>
              <td align="center" valign="middle">EED</td>
              <td align="center" valign="middle">EED foi segura e acurada para diagn&#243;stico de estenose de art&#233;rias coron&#225;rias em crian&#231;as</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Noto et al. (2014)<sup><xref ref-type="bibr" rid="B340">340</xref></sup></td>
              <td align="center" valign="middle">58</td>
              <td align="center" valign="middle">23,8 anos (m&#233;dia)</td>
              <td align="center" valign="middle">EED</td>
              <td align="center" valign="middle">EED foi &#250;til na estratifica&#231;&#227;o de risco e na avalia&#231;&#227;o do progn&#243;stico</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle"><bold>Doen&#231;a Vascular do Enxerto P&#243;s-TX Card&#237;aco</bold><break/> Perez et al. (2022)<sup><xref ref-type="bibr" rid="B334">334</xref></sup></td>
              <td align="center" valign="middle">95</td>
              <td align="center" valign="middle">16,3 anos (mediana)</td>
              <td align="center" valign="middle">EEF/esteira</td>
              <td align="center" valign="middle">EEF alterada foi associada ao &#8593;de risco para eventos CV e &#243;bito, enquanto EEF normal foi associada &#224; sobrevida livre de eventos CV</td>
            </tr>
            <tr>
              <td align="left" valign="middle"><bold>OAAC</bold><break/>Brothers et al. (2007)<sup><xref ref-type="bibr" rid="B341">341</xref></sup></td>
              <td align="center" valign="middle">24</td>
              <td align="center" valign="middle">24 anos (mediana)</td>
              <td align="center" valign="middle">EEF/esteira e bicicleta</td>
              <td align="center" valign="middle">EEF foi &#250;til para avalia&#231;&#227;o de isquemia e no cuidado p&#243;s-operat&#243;rio</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle"><bold>PO Cirurgia de Jatene</bold><break/> Chen et al. (2013)<sup><xref ref-type="bibr" rid="B342">342</xref></sup></td>
              <td align="center" valign="middle">32</td>
              <td align="center" valign="middle">16,2 &#177; 2,1 (m&#233;dia &#177; DP)</td>
              <td align="center" valign="middle">EEF/bicicleta</td>
              <td align="center" valign="middle">EEF demonstrou reserva contr&#225;til diminu&#237;da em adolescentes e em adultos jovens no PO</td>
            </tr>
            <tr>
              <td align="left" valign="middle"><bold>Sobreviventes de C&#226;ncer infantil</bold><break/> Ryerson et al. (2015)<sup><xref ref-type="bibr" rid="B343">343</xref></sup></td>
              <td align="center" valign="middle">80</td>
              <td align="center" valign="middle">13 anos (m&#233;dia)</td>
              <td align="center" valign="middle">EEF/bicicleta</td>
              <td align="center" valign="middle">Pacientes apresentaram melhora da fun&#231;&#227;o diast&#243;lica e sist&#243;lica no exerc&#237;cio sugerindo capacidade de compensar disfun&#231;&#227;o card&#237;aca leve</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle"><bold>PO Cirurgia de Ross</bold><break/> Pauliks et al. (2012)<sup><xref ref-type="bibr" rid="B339">339</xref></sup></td>
              <td align="center" valign="middle">26</td>
              <td align="center" valign="middle">14,9 anos (m&#233;dia)</td>
              <td align="center" valign="middle">EEF/esteira</td>
              <td align="center" valign="middle">EEF foi vi&#225;vel em crian&#231;as e a maioria apresentou capacidade ao exerc&#237;cio normal</td>
            </tr>
            <tr>
              <td align="left" valign="middle"><bold>PO T4F</bold><break/> Bhatt et al. (2019)<sup><xref ref-type="bibr" rid="B344">344</xref></sup></td>
              <td align="center" valign="middle">29</td>
              <td align="center" valign="middle">18.3 &#177; 4.83<break/> &#8595; performance ao exerc&#237;cio<break/> 12.8 &#177; 3.26<break/> &#8593; performance ao exerc&#237;cio (m&#233;dia &#177; DP)</td>
              <td align="center" valign="middle">EEF/esteira</td>
              <td align="center" valign="middle">A resposta cronotr&#243;pica preservada, mais do que reserva contr&#225;til do VD, foi um fator importante para o desempenho ao exerc&#237;cio</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle"><bold>Estenose de Tubo VD-TP</bold><break/> Hasan et al. (2012)<sup><xref ref-type="bibr" rid="B345">345</xref></sup></td>
              <td align="center" valign="middle">40</td>
              <td align="center" valign="middle">17 anos (mediana)</td>
              <td align="center" valign="middle">EEF/esteira</td>
              <td align="center" valign="middle">EEF detectou disfun&#231;&#227;o do VD e do tubo no pico do exerc&#237;cio</td>
            </tr>
            <tr>
              <td align="left" valign="middle"><bold>Gradiente na VSVE na CMH</bold><break/> El Assaad et al. (2020)<sup><xref ref-type="bibr" rid="B346">346</xref></sup></td>
              <td align="center" valign="middle">91</td>
              <td align="center" valign="middle">12 anos (mediana)</td>
              <td align="center" valign="middle">EEF/esteira e bicicleta</td>
              <td align="center" valign="middle">EEF foi segura e demonstrou ser efetiva na identifica&#231;&#227;o de pacientes de baixo risco para eventos CV</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN13">
            <p>CMH: cardiomiopatia hipertr&#243;fica; CV: cardiovasculares; DP: desvio padr&#227;o; EED: ecocardiografia de estresse com dobutamina; EEF: ecocardiografia de estresse f&#237;sico; OAAC: origem an&#244;mala a&#243;rtica das art&#233;rias coron&#225;rias; PO: p&#243;s-operat&#243;rio; TP: tronco pulmonar; TX: transplante; VE: ventr&#237;culo esquerdo; VSVE: via de sa&#237;da de ventr&#237;culo esquerdo; &#916;P: gradiente press&#243;rico; VD: ventr&#237;culo direito.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <table-wrap id="t24">
        <label>Tabela 30.2</label>
        <caption>
          <title>Indica&#231;&#245;es simplificadas da ecocardiografia de estresse em crian&#231;as, adolescentes e adultos jovens</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="middle" rowspan="4">Indica&#231;&#245;es de ecocardiografia de estresse em pediatria</td>
              <td align="left" valign="middle">Suspeita de doen&#231;a arterial coronariana: Doen&#231;a de Kawasaki, vasculopatia do enxerto p&#243;s transplante, opera&#231;&#245;es que envolvem transloca&#231;&#227;o coronariana, como o switch arterial na transposi&#231;&#227;o das grandes art&#233;rias, origens ou cursos an&#244;malos das art&#233;rias coron&#225;rias, atresia pulmonar com septo ventricular intacto, hiperlipidemia, diabetes mellitus dependente de insulina e estenose a&#243;rtica supravalvar</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">P&#243;s quimioterapia: Antraciclinas</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Avalia&#231;&#245;es de gradientes:Cardiomiopatia hipertr&#243;fica ou estenose a&#243;rtica e pulmonar</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">Avalia&#231;&#245;es daresposta hemodin&#226;mica e mioc&#225;rdica em condi&#231;&#245;es espec&#237;ficas: hipertens&#227;o pulmonar, cardiomiopatia dilatada, cardiopatias cong&#234;nitas, regurgita&#231;&#227;o mitral e a&#243;rtica.</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <p>Para indica&#231;&#245;es espec&#237;ficas, os protocolos s&#227;o ajustados para incluir, por exemplo, imagens Doppler das valvas atrioventriculares para estudar a regurgita&#231;&#227;o da valva a&#243;rtica ou medir gradientes nas vias de sa&#237;da.</p>
      <p>Nos pacientes pedi&#225;tricos, ao contr&#225;rio dos adultos, n&#227;o h&#225; dados suficientes sobre o valor progn&#243;stico e impacto cl&#237;nico da ecocardiografia de estresse na avalia&#231;&#227;o din&#226;mica dos gradientes na estenose a&#243;rtica e na estenose pulmonar.<sup><xref ref-type="bibr" rid="B333">333</xref>,<xref ref-type="bibr" rid="B339">339</xref></sup></p>
      <p>Por fim, a ecocardiografia de estresse &#233; ainda &#225;rea em desenvolvimento na cardiologia pedi&#225;trica. Sua integra&#231;&#227;o com o Doppler tecidual e tecnologia de <italic>strain</italic> tem permitido uma an&#225;lise mais quantitativa da fun&#231;&#227;o sist&#243;lica e diast&#243;lica regional e global nesse cen&#225;rio, mas ainda de modo incipiente. A colabora&#231;&#227;o entre cardiologistas adultos e pedi&#225;tricos &#233; necess&#225;ria para que protocolos visando as particularidades das crian&#231;as sejam implementados e essa modalidade de exame seja mais utilizada nesse subgrupo.</p>
    </sec>
    <sec>
      <title>31. Vantagens e Desvantagens da Ecocardiografia de Estresse em Pediatria</title>
      <p>Tanto a EEF quanto a de estresse farmacol&#243;gico podem ser utilizadas em pediatria.<sup><xref ref-type="bibr" rid="B33">33</xref>,<xref ref-type="bibr" rid="B99">99</xref>,<xref ref-type="bibr" rid="B347">347</xref></sup> Contudo, o m&#233;dico deve considerar as vantagens e desvantagens de cada abordagem para orientar os testes na popula&#231;&#227;o pedi&#225;trica (<xref ref-type="table" rid="t25">Tabela 31.1</xref>).</p>
      <table-wrap id="t25">
        <label>Tabela 31.1</label>
        <caption>
          <title>Vantagens e desvantagens de cada abordagem para orientar a testagem na popula&#231;&#227;o pedi&#225;trica</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 style="background-color:#76B4CF">
              <th align="left" valign="middle">Modalidade de Imagem</th>
              <th align="center" valign="middle">Vantagens</th>
              <th align="center" valign="middle">Desvantagens</th>
              <th align="center" valign="middle">Usos</th>
            </tr>
          </thead>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr>
              <td align="left" valign="middle">Ecocardiograma de estresse f&#237;sico (EEF)</td>
              <td align="center" valign="middle">N&#227;o exige pun&#231;&#227;o intravenosa<break/> N&#227;o exige seda&#231;&#227;o<break/> Poss&#237;vel obter outros dados &#8211; ECG e possivelmente VO<sub>2</sub></td>
              <td align="center" valign="middle">Equipamento adicional<break/> Paciente deve conseguir realizar exerc&#237;cio em erg&#244;metro</td>
              <td align="center" valign="middle"/>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">EEF de esteira</td>
              <td align="center" valign="middle">Semelhante a atividades da vida di&#225;ria<break/> VO<sub>2</sub> m&#225;x mais elevado<break/> Pode ser mais f&#225;cil induzir isquemia</td>
              <td align="center" valign="middle">Artefato de movimento<break/> Recupera&#231;&#227;o da frequ&#234;ncia card&#237;aca r&#225;pida em crian&#231;as<break/> Necessita transfer&#234;ncia para leito</td>
              <td align="center" valign="middle">Avalia&#231;&#227;o de Isquemia<break/> Obstru&#231;&#227;o do fluxo de VSVE<break/> Reserva contr&#225;til</td>
            </tr>
            <tr>
              <td align="left" valign="middle">EEF de bicicleta ergom&#233;trica</td>
              <td align="center" valign="middle">Obten&#231;&#227;o das imagens em v&#225;rios momentos<break/> Menos artefatos de movimento<break/> Doppler pode ser poss&#237;vel</td>
              <td align="center" valign="middle">Coopera&#231;&#227;o em crian&#231;as menores<break/> Frequ&#234;ncia card&#237;aca mais baixa<break/> VO<sub>2</sub> mais baixo</td>
              <td align="center" valign="middle">Regurgita&#231;&#227;o valvar<break/> Estenose valvar atrioventricular<break/> Hipertens&#227;o pulmonar<break/> Disfun&#231;&#227;o diast&#243;lica</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">Eco de estresse farmacol&#243;gico</td>
              <td align="center" valign="middle">Menos interfer&#234;ncia pulmonar<break/> N&#227;o necessita transfer&#234;ncia para leito<break/> Reduz problemas associados &#224; recupera&#231;&#227;o da frequ&#234;ncia card&#237;aca</td>
              <td align="center" valign="middle">Coloca&#231;&#227;o de linha intravenosa</td>
              <td align="center" valign="middle"/>
            </tr>
            <tr>
              <td align="left" valign="middle">Eco de estresse com dobutamina</td>
              <td align="center" valign="middle">Afeta frequ&#234;ncia card&#237;aca e press&#227;o arterial</td>
              <td align="center" valign="middle">Demora cerca de 20 minutos<break/> Perfil de efeitos colaterais: arritmias ventriculares, emerg&#234;ncia hipertensiva, n&#225;usea/v&#244;mito</td>
              <td align="center" valign="middle">Obstru&#231;&#227;o coron&#225;ria din&#226;mica<break/> Baixa dose &#8211; estenose a&#243;rtica de baixo fluxo e baixo gradiente</td>
            </tr>
            <tr style="background-color:#C7DFEC">
              <td align="left" valign="middle">Eco de estresse com vasodilatador</td>
              <td align="center" valign="middle">Curta dura&#231;&#227;o</td>
              <td align="center" valign="middle">Perfil de efeitos colaterais: sibil&#226;ncia, convuls&#245;es, hipotens&#227;o</td>
              <td align="center" valign="middle">Obstru&#231;&#227;o coron&#225;ria fixa</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <p>A EEF apresenta algumas vantagens sobre o estresse farmacol&#243;gico na popula&#231;&#227;o pedi&#225;trica. Primeiro, n&#227;o h&#225; necessidade de obter acesso intravenoso para o estresse f&#237;sico, minimizando o sofrimento do paciente pedi&#225;trico. Segundo, n&#227;o h&#225; necessidade de seda&#231;&#227;o, que pode ser necess&#225;ria para per&#237;odos de estudo mais longos associados a agentes farmacol&#243;gicos. Por fim, o ecocardiografista muitas vezes pode escolher entre dois erg&#244;metros para a ecocardiografia de esfor&#231;o: uma esteira ergom&#233;trica ou um cicloerg&#244;metro.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B331">331</xref>,<xref ref-type="bibr" rid="B341">341</xref>,<xref ref-type="bibr" rid="B346">346</xref>,<xref ref-type="bibr" rid="B348">348</xref>-<xref ref-type="bibr" rid="B350">350</xref></sup></p>
      <p>A ecocardiografia de exerc&#237;cio tamb&#233;m apresenta v&#225;rias desvantagens. Primeiro, o equipamento adicional necess&#225;rio pode ser limitante para alguns laborat&#243;rios, dada a necessidade do transdutor pedi&#225;trico e do software de estresse. Al&#233;m disso, a ecocardiografia de exerc&#237;cio requer coopera&#231;&#227;o significativa do paciente pedi&#225;trico, independentemente do erg&#244;metro utilizado. Artefatos pulmonares devido a um aumento fisiol&#243;gico na frequ&#234;ncia respirat&#243;ria podem limitar as janelas ecocardiogr&#225;ficas junto ao exerc&#237;cio desse subgrupo de pacientes pouco cooperativos. Por fim, a recupera&#231;&#227;o r&#225;pida da FC em crian&#231;as pode limitar a capacidade de obter imagens adequadas no pico de estresse.</p>
      <p>O tipo de erg&#244;metro selecionado tem vantagens e desvantagens espec&#237;ficas. As esteiras ergom&#233;tricas se assemelham muito &#224;s atividades di&#225;rias e de academias. Al&#233;m disso, geralmente &#233; alcan&#231;ado um VO<sub>2</sub> mais elevado, que &#233; muito bom, assim como o maior duplo produto. A principal desvantagem das esteiras ergom&#233;tricas &#233; que o paciente deve ser capaz de se transferir de forma r&#225;pida e segura da esteira para a cama de ecocardiografia devido ao r&#225;pido tempo de queda e recupera&#231;&#227;o da FC na popula&#231;&#227;o pedi&#225;trica<sup><xref ref-type="bibr" rid="B3">3</xref></sup> e o examinador precisa obter essas imagens em curto espa&#231;o de tempo. Isso nem sempre &#233; f&#225;cil, especialmente em crian&#231;as.</p>
      <p>Os cicloerg&#244;metros supinos permitem imagens em v&#225;rios per&#237;odos de tempo durante o teste de esfor&#231;o, com monitoriza&#231;&#227;o cont&#237;nua. Os cicloerg&#244;metros podem permitir a utiliza&#231;&#227;o do Doppler colorido ou espectral de maneira gradual e mais adequada nesse subgrupo, o que pode ser vantajoso ao observar estenose ou regurgita&#231;&#227;o valvar e hipertens&#227;o pulmonar,<sup><xref ref-type="bibr" rid="B3">3</xref></sup> obstru&#231;&#227;o intraventricular na CMH e gradientes na estenose a&#243;rtica.<sup><xref ref-type="bibr" rid="B346">346</xref>,<xref ref-type="bibr" rid="B350">350</xref></sup> Al&#233;m disso, os cicloerg&#244;metros tendem a limitar os artefatos de movimento. Contudo, a coopera&#231;&#227;o pode ser mais dif&#237;cil em pacientes mais jovens, pois estes devem continuar a pedalar em um ritmo constante. Normalmente, VO<sub>2</sub> mais baixo e frequ&#234;ncias card&#237;acas mais baixas s&#227;o alcan&#231;ados com cicloerg&#244;metros em compara&#231;&#227;o com esteiras ergom&#233;tricas.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
      <p>A ecocardiografia de estresse farmacol&#243;gico tamb&#233;m pode ser realizada em crian&#231;as.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B351">351</xref>,<xref ref-type="bibr" rid="B352">352</xref>,<xref ref-type="bibr" rid="B340">340</xref></sup> Por&#233;m, a principal desvantagem &#233; a necessidade de acesso intravenoso para administra&#231;&#227;o do agente farmacol&#243;gico. As vantagens incluem menor interfer&#234;ncia pulmonar, avalia&#231;&#227;o em v&#225;rios n&#237;veis do teste e n&#227;o necessidade de transfer&#234;ncia para uma cama para obten&#231;&#227;o de imagens. Esta t&#233;cnica limita os problemas associados &#224; recupera&#231;&#227;o r&#225;pida da FC em crian&#231;as, uma vez que a monitoriza&#231;&#227;o ecocardiogr&#225;fica &#233; cont&#237;nua.</p>
      <p>Os dois principais agentes farmacol&#243;gicos utilizados s&#227;o a dobutamina e os vasodilatadores.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> A dobutamina simula o exerc&#237;cio, aumentando a FC e a PA para n&#237;veis pr&#243;ximos ao exerc&#237;cio m&#225;ximo. &#201; utilizado principalmente para provocar isquemia e anormalidade da motilidade parietal em &#225;reas onde possa haver obstru&#231;&#227;o din&#226;mica do fluxo arterial coron&#225;rio em crian&#231;as, e tamb&#233;m na avalia&#231;&#227;o de origem an&#244;mala das art&#233;rias coron&#225;rias ou em receptores de transplante.<sup><xref ref-type="bibr" rid="B341">341</xref>,<xref ref-type="bibr" rid="B349">349</xref>,<xref ref-type="bibr" rid="B351">351</xref>,<xref ref-type="bibr" rid="B352">352</xref></sup></p>
      <p>Os vasodilatadores, como o dipiridamol, a adenosina ou o regadenoson, dilatam as art&#233;rias coron&#225;rias normais, causando isquemia e anormalidades na motilidade parietal em &#225;reas onde h&#225; obstru&#231;&#227;o coron&#225;ria fixa.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Podem ser &#250;teis especialmente na avalia&#231;&#227;o da doen&#231;a de Kawasaki e de art&#233;rias coron&#225;rias reimplantadas. Os perfis de efeitos colaterais variam de acordo com o vasodilatador utilizado, como descrito anteriormente.</p>
      <p>Apesar de haver muitas op&#231;&#245;es de ecocardiografia de estresse, ela permanece subutilizada em crian&#231;as. Os m&#233;dicos que compreendem as vantagens e desvantagens de cada modalidade podem selecionar a op&#231;&#227;o mais apropriada para cada quest&#227;o cl&#237;nica.</p>
    </sec>
    <sec>
      <title>32. Progn&#243;stico da Ecocardiografia de Estresse</title>
      <p>A indu&#231;&#227;o de isquemia mioc&#225;rdica causada por aumento da FC &#8805;85% de acordo com a idade, durante a ecocardiografia de estresse por esfor&#231;o f&#237;sico ou por infus&#227;o intravenosa de dobutamina, &#233; um m&#233;todo eficaz para o manejo cl&#237;nico e progn&#243;stico da cardiopatia isqu&#234;mica. A resposta normal &#233; um aumento contr&#225;til de todos os 16-17 segmentos ventriculares.<sup><xref ref-type="bibr" rid="B202">202</xref></sup> &#192; resposta de cada segmento, seja normal ou hipercin&#233;tica, &#233; atribu&#237;do um valor de 1 (hipocinesia leve ou moderada) 2 (hipocinesia grave), 3 (acinesia), 4 ou 5 (discinesia). Para simplificar, atualmente utiliza-se mais o seguinte esquema: 1 = normal ou hipercin&#233;tico, 2 = hipocin&#233;tico (em qualquer grau), 3 = acin&#233;tico e 4 = aneurisma. A soma permite calcular o WMSI pela divis&#227;o de todos os segmentos exibidos por 16 ou 17 segmentos analisados. O resultado normal &#233; 16/16 = 1 ou 17/17=1 e indica contratilidade global normal. Em um exemplo anormal, a hipocinesia moderada de dois segmentos soma 4, mais acinesia 4 de um segmento, soma 8, divide 16/8 e o WMSI &#233; 2, anormal.</p>
      <p>Em 3.121 pacientes<sup><xref ref-type="bibr" rid="B202">202</xref></sup> divididos em tr&#234;s grupos de risco de acordo com WMS acompanhados por 3 anos, WMSI de baixo risco de 1 teve eventos de 0,8% ao ano; com WMSI de 1,1-1,7 o risco intermedi&#225;rio, de 2,6% ao ano; e com alto risco de WMS &gt; 1,7, os eventos foram de 5,5% por ano.</p>
      <p>Outro estudo, com 1.560 pacientes, relacionou o pico do WMSI com a FEVE.<sup><xref ref-type="bibr" rid="B353">353</xref></sup> Os participantes foram divididos em tr&#234;s grupos com seguimento de 3 anos. O estudo observou que o risco baixo teve &#237;ndice de eventos de 0,7%/ano, o intermedi&#225;rio 2,0%/ano e o alto 4,4%/ano. Os eventos foram infarto do mioc&#225;rdio, morte ou outras complica&#231;&#245;es cardiovasculares.</p>
      <p>Em 2.575 indiv&#237;duos portadores de DAC com ecocardiografia de estresse de pico negativo,<sup><xref ref-type="bibr" rid="B354">354</xref></sup> classificados em dois grupos, sem altera&#231;&#227;o contr&#225;til em repouso ou durante exerc&#237;cio m&#225;ximo, ou com altera&#231;&#227;o contr&#225;til pr&#233;via (por infarto) n&#227;o agravada durante a ecocardiografia de estresse, o crit&#233;rio de anormalidade foi o desenvolvimento de nova les&#227;o coronariana &#8805;50% em um ano. A mortalidade por qualquer causa em indiv&#237;duos com resultados negativos em 1 ano foi de 1,1% e naqueles com doen&#231;a coronariana pr&#233;via foi de 3,1%/ano. Os preditores de novas les&#245;es coronarianas em um ano foram sexo masculino, diabetes, doen&#231;a coronariana pr&#233;via e ecocardiografia de estresse n&#227;o isqu&#234;mico por&#233;m anormal. Esses pacientes com ecocardiografia de estresse negativa devem ser acompanhados devido ao maior risco de morbidade e mortalidade, mesmo que o resultado do exame atual seja negativo.</p>
      <p>Em 609 pacientes com BRE<sup><xref ref-type="bibr" rid="B355">355</xref></sup> investigados com ecocardiografia de estresse de exerc&#237;cio, com acompanhamento de quase 5 anos, o WMSI foi obtido em repouso e p&#243;s-exerc&#237;cio. A diferen&#231;a do WMSI (delta) entre os dois momentos do teste foi de 29%. A mortalidade de pacientes com isquemia foi de 25% e n&#227;o isquemia de 13%.</p>
      <p>Os eventos card&#237;acos maiores foram de 18% vs. 10% e o delta do WMSI &#233; considerado um preditor independente.</p>
      <p>A ecocardiografia de estresse tem maior valor preditivo em rela&#231;&#227;o aos demais par&#226;metros cl&#237;nicos.</p>
      <p>As principais causas da finaliza&#231;&#227;o/interrup&#231;&#227;o do exame s&#227;o: aparecimento ou agravamento da altera&#231;&#227;o contr&#225;til, angina pectoris, altera&#231;&#245;es isqu&#234;micas no ECG, arritmias significativas, hipertens&#227;o arterial ou hipotens&#227;o significativas, dispneia ou fadiga limitantes e tremor intenso. A finaliza&#231;&#227;o do teste por interrup&#231;&#227;o ou por chegar ao final do protocolo sem atingir os <italic>endpoints</italic> de altera&#231;&#227;o contr&#225;til ou obten&#231;&#227;o da FC alvo deve ser relatada no laudo.</p>
      <p>Diretrizes de ecocardiografia de estresse que tratam sobre os riscos e progn&#243;stico futuro do m&#233;todo foram publicadas recentemente.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup></p>
    </sec>
    <sec>
      <title>33. Novas Aplica&#231;&#245;es da Ecocardiografia de Estresse no P&#243;s-Radioterapia de T&#243;rax e no Vasoespasmo</title>
      <p>A radioterapia (RT) &#233; um dos pilares do tratamento oncol&#243;gico. Doses elevadas de radia&#231;&#227;o no t&#243;rax s&#227;o usadas com frequ&#234;ncia no tratamento de c&#226;ncer de pulm&#227;o, es&#244;fago, sistema linf&#225;tico e mama. Devido &#224; proximidade anat&#244;mica, o cora&#231;&#227;o invariavelmente recebe doses de radia&#231;&#227;o que podem induzir cardiotoxicidade. Estudos mostram que a RT acelera o processo de aterosclerose coronariana, calcifica&#231;&#227;o valvar e fibrose pulmonar e do peric&#225;rdio.</p>
      <p>A toxicidade cardiovascular (CV) relacionada &#224; RT &#233; progressiva, tipicamente se desenvolve 5 a 10 anos ap&#243;s o tratamento inicial e pode causar DAC e insufici&#234;ncia card&#237;aca (IC) com incid&#234;ncia at&#233; seis vezes maior do que na popula&#231;&#227;o geral. A lat&#234;ncia entre a RT e o aparecimento da DAC varia de alguns anos a v&#225;rias d&#233;cadas, dependendo do risco CV pr&#233;-tratamento, idade do paciente, doses acumuladas de RT e tratamentos combinados com quimioterapia.<sup><xref ref-type="bibr" rid="B356">356</xref></sup> Uma avalia&#231;&#227;o minuciosa dos riscos CV com escores de riscos amplamente difundidos, assim como a avalia&#231;&#227;o de altera&#231;&#245;es card&#237;acas preexistentes, se torna fundamental.</p>
      <p>Ao considerar que o paciente submetido a RT normalmente possui uma grande carga acumulada de radia&#231;&#227;o, m&#233;todos de imagem que n&#227;o exigem doses extras se tornam priorit&#225;rios.<sup><xref ref-type="bibr" rid="B357">357</xref>,<xref ref-type="bibr" rid="B358">358</xref></sup></p>
      <p>A ecocardiografia de estresse e a busca por altera&#231;&#227;o de contratilidade regional e fun&#231;&#227;o ventricular esquerda s&#227;o o protocolo mais seguido nos &#250;ltimos 40 anos.</p>
      <p>Em artigo recente, um grupo de estudiosos liderado pelo Dr. Eugenio Picano sugere um protocolo ABCDE expandido, que inclui os passos F, G, P e R devido &#224; complexidade multivariada das causas de dano. A avalia&#231;&#227;o valvar mitral, a da progress&#227;o de sua calcifica&#231;&#227;o e a repercuss&#227;o frente ao estresse formam o passo F. A avalia&#231;&#227;o da progress&#227;o da calcifica&#231;&#227;o valvar a&#243;rtica e seu gradiente s&#227;o o passo G. Testar a resist&#234;ncia vascular pulmonar &#233; o passo P e as altera&#231;&#245;es da fun&#231;&#227;o do VD representam o passo R.<sup><xref ref-type="bibr" rid="B359">359</xref></sup></p>
      <p>Informa&#231;&#245;es adicionais podem ser relevantes e devem ser estimuladas quando poss&#237;vel. Uma avalia&#231;&#227;o pr&#233;-exame minuciosa e um exame de estresse direcionado com &#234;nfase priorit&#225;ria na d&#250;vida diagn&#243;stica, baseado no bom senso cl&#237;nico, parecem ser o mais adequado.</p>
      <p>O vasoespasmo coronariano &#233; umas das principais causas de estenose din&#226;mica das art&#233;rias coron&#225;rias e pode causar angina, angina inst&#225;vel, infarto agudo do mioc&#225;rdio, s&#237;ncope e morte s&#250;bita. Seu diagn&#243;stico continua a ser um grande desafio cl&#237;nico. O teste provocativo invasivo com ergonovina foi descrito em v&#225;rios estudos, com algumas ressalvas, como mencionado anteriormente. O estudo invasivo exp&#245;e o paciente a radia&#231;&#227;o e a contrastes que podem ser nefrot&#243;xicos, al&#233;m da ergonovina n&#227;o estar dispon&#237;vel comercialmente em v&#225;rios pa&#237;ses. Estudos descrevem protocolos n&#227;o invasivos com ergonovina, adenosina ou dobutamina.<sup><xref ref-type="bibr" rid="B360">360</xref></sup> Por&#233;m, o protocolo que tem se mostrado mais promissor &#233; o de hiperventila&#231;&#227;o (5 minutos de hiperventila&#231;&#227;o com frequ&#234;ncia respirat&#243;ria de 25 ipm) combinada com exerc&#237;cio em bicicleta (incremento de 25 W a cada 2-3 min). Esses dois passos podem esclarecer se a angina &#233; por vasoespasmo, ao alterar a contratilidade regional (passo A), ou por disfun&#231;&#227;o microvascular coronariana (passo D). Estudos de valida&#231;&#227;o, teste de efic&#225;cia e seguran&#231;a em larga escala desse protocolo ainda s&#227;o necess&#225;rios. Dados adicionais devem ser publicados ap&#243;s a conclus&#227;o do estudo Stress Echo 2030.<sup><xref ref-type="bibr" rid="B261">261</xref></sup></p>
    </sec>
    <sec>
      <title>34. Ecocardiografia de Estresse com o Protocolo ABCDE</title>
      <p>O teste funcional com ecocardiografia de estresse se baseia na detec&#231;&#227;o de anormalidades da motilidade regional com ecocardiografia bidimensional e est&#225; incorporado nas diretrizes cl&#237;nicas. No entanto, subutiliza a versatilidade &#250;nica da t&#233;cnica, ideal para descrever as diferentes anormalidades funcionais subjacentes &#224; mesma resposta ao movimento da parede durante o estresse. O protocolo ABCDE, idealizado pelo Dr Eugenio Picano na It&#225;lia, iniciou com o estudo multic&#234;ntrico Stress Echo 2020 e posteriormente o Stress Echo 2030, com o objetivo de transcender a utiliza&#231;&#227;o da ecocardiografia de estresse para uma gama de aplica&#231;&#245;es onde ela pode acrescentar informa&#231;&#245;es relevantes<sup><xref ref-type="bibr" rid="B261">261</xref></sup> (<xref ref-type="fig" rid="f36">Figura 34.1</xref>).</p>
      <fig id="f36">
        <label>Figura 34.1</label>
        <caption>
          <title>O "cora&#231;&#227;o" do protocolo ABCDE do Stress Echo 2030.<sup><xref ref-type="bibr" rid="B261">261</xref></sup></title>
        </caption>
        <graphic xlink:href=""/>
      </fig>
      <p>Cinco par&#226;metros convergem conceitual e metodologicamente no protocolo ABCDE,<sup><xref ref-type="bibr" rid="B261">261</xref></sup> avaliando m&#250;ltiplas vulnerabilidades do paciente isqu&#234;mico.</p>
      <p>As cinco etapas do protocolo ABCDE s&#227;o: 1) A: movimento/espessamento regional da parede (amplamente difundida); 2) B: linhas B por ultrassonografia pulmonar avaliando congest&#227;o pulmonar extravascular; 3) C: reserva contr&#225;til do VE por ecocardiografia volum&#233;trica bidimensional; 4) D: reserva de velocidade de fluxo coronariano na coron&#225;ria descendente anterior m&#233;dio-distal esquerda com Doppler puls&#225;til; e 5) E: avalia&#231;&#227;o da FC por eletrocardiografia com uma deriva&#231;&#227;o.</p>
      <p>A ecocardiografia de estresse ABCDE oferece informa&#231;&#245;es sobre cinco reservas funcionais: fluxo epic&#225;rdico (A); reserva diast&#243;lica/congest&#227;o (B), reserva contr&#225;til (C), microcircula&#231;&#227;o coronariana (D) e reserva cronotr&#243;pica (E) (<xref ref-type="fig" rid="f37">Figura 34.2</xref>).</p>
      <fig id="f37">
        <label>Figura 34.2</label>
        <caption>
          <title>Integra&#231;&#227;o de quatro principais imagens &#224; ecocardiografia de estresse. Os quatro objetivos fisiopatol&#243;gicos s&#227;o: avalia&#231;&#227;o da estenose epic&#225;rdica (A = assinergia), congest&#227;o pulmonar (B = linhas B), fun&#231;&#227;o mioc&#225;rdica do VE (C = reserva contr&#225;til) e fun&#231;&#227;o microvascular coronariana (D = Doppler RFC), E = reserva cronotr&#243;pica, que pode ser avaliada adicionalmente.<sup><xref ref-type="bibr" rid="B261">261</xref></sup> RFC: reserva de fluxo coronariano; WMSI: Wall Motion Score Index - Em portugu&#234;s, &#205;ndice de Escore da Motilidade da Parede; RCVE: Reserva Contr&#225;til do Ventr&#237;culo Esquerdo; FC: Frequ&#234;ncia Card&#237;aca.</title>
        </caption>
        <graphic xlink:href=""/>
      </fig>
      <p>O novo formato &#233; mais abrangente e permite melhor caracteriza&#231;&#227;o funcional, estratifica&#231;&#227;o de risco e adapta&#231;&#227;o personalizada da terapia institu&#237;da.</p>
      <p>O protocolo ABCDE<sup><xref ref-type="bibr" rid="B261">261</xref></sup> &#233; um teste funcional adequado para todos os tipos de estresse e todos os pacientes e vai al&#233;m da DAC. Ele responde &#224; necessidade de sustentabilidade nos cuidados de sa&#250;de, uma vez que requer tecnologia universalmente dispon&#237;vel e &#233; de baixo custo, isento de radia&#231;&#227;o e praticamente in&#243;cuo.</p>
      <sec>
        <title>34.1. Protocolo ABCDE</title>
        <list list-type="bullet">
          <list-item>
            <p>
              <bold>A para Assinergia:</bold>
            </p>
            <p>&#201; baseado na suposta contratilidade mioc&#225;rdica, ou seja, altera&#231;&#227;o induzida por estresse na presen&#231;a de limita&#231;&#227;o de fluxo pela estenose coronariana. O desequil&#237;brio entre oferta e demanda de oxig&#234;nio leva &#224; redu&#231;&#227;o do espessamento radial do mioc&#225;rdio, par&#226;metro &#224;s vezes limitado por sua natureza semiquantitativa e subjetiva. A depend&#234;ncia do operador pode ser minimizada (mas n&#227;o eliminada) por treinamento especializado e pela ado&#231;&#227;o de medidas como a acredita&#231;&#227;o e o controle de qualidade dos laborat&#243;rios de ecocardiografia.</p>
            <p>A avalia&#231;&#227;o da motilidade regional indica que quanto maior o n&#250;mero de segmentos afetados (definidos universalmente), pior o progn&#243;stico. Esse par&#226;metro &#233; centrado na DAC.</p>
          </list-item>
          <list-item>
            <p>
              <bold>B para Linhas-B:</bold>
            </p>
            <p>O aumento da press&#227;o atrial esquerda constitui a base de diversas condi&#231;&#245;es. Sua consequ&#234;ncia fisiopatol&#243;gica tem rela&#231;&#227;o com a sa&#237;da de l&#237;quido no interst&#237;cio pulmonar e pericapilar como substrato hidrost&#225;tico. Na sua forma aguda, esse l&#237;quido pode ser detectado por ultrassom na forma de linhas de eco que &#233; capaz de reverber&#225;-lo. Durante a EEF, a indu&#231;&#227;o de processos fisiol&#243;gicos que podem provocar o limite da homeostase da doen&#231;a &#233; um par&#226;metro com valor progn&#243;stico significativo.<sup><xref ref-type="bibr" rid="B361">361</xref></sup></p>
          </list-item>
          <list-item>
            <p>
              <bold>C para Contratilidade:</bold>
            </p>
            <p>A contratilidade &#233; a capacidade inerente do mioc&#225;rdio de se contrair independentemente de altera&#231;&#245;es na pr&#233; ou p&#243;s-carga.</p>
            <p>Durante a ecocardiografia de estresse, o volume sist&#243;lico final do VE (VSF) &#233; progressivamente menor, resultando em picos de PA mais elevados e aumento da carga. A rela&#231;&#227;o entre a PAS e o VSF prediz a capacidade de esvaziamento do VE.<sup><xref ref-type="bibr" rid="B362">362</xref></sup></p>
            <p>A elast&#226;ncia do VE mede a reserva contr&#225;til por meio da compara&#231;&#227;o do seu desempenho em repouso e condi&#231;&#245;es de estresse. Essa medida pode ser obtida pela divis&#227;o da rela&#231;&#227;o PAS/VSF em condi&#231;&#245;es de estresse, pelas condi&#231;&#245;es de repouso.</p>
            <p>O estresse f&#237;sico e com dobutamina tem valores validados, se estes est&#227;o acima de 2,0; e com o uso de vasodilatadores, a propor&#231;&#227;o que indica contratilidade apropriada est&#225; acima de 1,1.</p>
          </list-item>
          <list-item>
            <p>
              <bold>D para Doppler da Art&#233;ria Coron&#225;ria:</bold>
            </p>
            <p>O fluxo coronariano pode ser afetado por condi&#231;&#245;es epic&#225;rdicas de estenose e disfun&#231;&#227;o muscular.</p>
            <p>No primeiro cen&#225;rio, em um determinado ponto de medida da vaz&#227;o, pode ocorrer uma limita&#231;&#227;o pelo fluxo de sangue comprometido a jusante da obstru&#231;&#227;o em situa&#231;&#245;es de estresse.</p>
            <p>Na segunda, diversas condi&#231;&#245;es podem ocorrer, tais como hipertrofia perivascular e les&#227;o do endot&#233;lio, altera&#231;&#227;o causada por inflama&#231;&#227;o e aterosclerose, impedindo o fluxo sangu&#237;neo adequado.</p>
            <p>A RFC &#233; medida por Doppler na ecocardiografia, usando a raz&#227;o de velocidade na regi&#227;o medial ou distal da ADA sob estresse e em condi&#231;&#245;es de repouso. Os valores normais s&#227;o aqueles acima de 2,0 em qualquer modalidade de ecocardiografia de estresse.</p>
          </list-item>
          <list-item>
            <p>
              <bold>E para Eletrocardiograma:</bold>
            </p>
            <p>A variabilidade da FC em resposta ao estresse pode fornecer informa&#231;&#245;es sobre a fun&#231;&#227;o auton&#244;mica do sistema de condu&#231;&#227;o card&#237;aca, constituindo um marcador durante o teste. Esse par&#226;metro, a reserva de FC, &#233; obtido pela divis&#227;o da FC m&#225;xima atingida pelo valor da FC em condi&#231;&#245;es de repouso.</p>
            <p>&#201; classificado como crit&#233;rio positivo se a rela&#231;&#227;o for inferior a 1,80, para estresse f&#237;sico ou dobutamina, e abaixo de 1,22 para vasodilatadores.</p>
            <p>Os betabloqueadores reduzem os valores da FC em condi&#231;&#245;es de repouso e estresse, mas sem impacto nessa rela&#231;&#227;o para fins progn&#243;sticos.<sup><xref ref-type="bibr" rid="B361">361</xref></sup></p>
          </list-item>
        </list>
        <p>Quando adicionado &#224; avalia&#231;&#227;o tradicional da ecocardiografia de estresse, o protocolo ABCDE resulta em um espectro mais amplo de vari&#225;veis avaliado pelo protocolo de estresse. Juntos, eles permitem melhor estratifica&#231;&#227;o de risco e auxiliam na defini&#231;&#227;o de diagn&#243;sticos mais precisos.</p>
        <p>Pacientes com doen&#231;as microvasculares e disfun&#231;&#227;o diast&#243;lica &#224;s vezes t&#234;m apresenta&#231;&#245;es at&#237;picas e podem se beneficiar desse novo protocolo, pois este amplia o poder diagn&#243;stico da ecocardiografia de estresse tradicional.<sup><xref ref-type="bibr" rid="B363">363</xref></sup></p>
        <p>O protocolo ABCDE prop&#245;e a plena utiliza&#231;&#227;o da ecocardiografia de estresse consolidada de forma simplificada para uma gama imensa de informa&#231;&#245;es adicionais, e apesar do maior consumo de tempo, vem ganhando espa&#231;o nos laborat&#243;rios de ecocardiografia por permitir maior ganho diagnostico.</p>
      </sec>
    </sec>
    <sec>
      <title>35. Recomenda&#231;&#245;es para o Manejo da Ecocardiografia de Estresse</title>
      <table-wrap id="t26">
        <caption>
          <title>ECO ESTRESSE NA DOEN&#199;A ISQU&#202;MICA CR&#212;NICA CONHECIDA OU SUSPEITA</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 style="background-color:#76B4CF">
              <th align="left" valign="middle">Recomenda&#231;&#245;es</th>
              <th align="center" valign="middle">For&#231;a de Recomenda&#231;&#227;o</th>
              <th align="center" valign="middle">Certeza da Evid&#234;ncia</th>
            </tr>
          </thead>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr>
              <td align="left" valign="middle">No diagn&#243;stico de doen&#231;a isqu&#234;mica cr&#244;nica em pacientes com probabilidade pr&#233;-teste intermedi&#225;ria.<break/> Na vig&#234;ncia de sintoma de angina em pacientes com stent ou revasculariza&#231;&#227;o pr&#233;vios.<break/> Na obstru&#231;&#227;o coron&#225;ria moderada pela angiotomografia ou angiografia coron&#225;ria: significado funcional.<break/> Na estratifica&#231;&#227;o de risco p&#243;s-infarto do mioc&#225;rdio. <break/>Na investiga&#231;&#227;o de dispneia (equivalente anginoso).</td>
              <td align="center" valign="middle" style="background-color:#00CC66">
                <bold>FORTE</bold>
              </td>
              <td align="center" valign="middle" style="background-color:#00B0F0">
                <bold>ALTA</bold>
              </td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <table-wrap id="t27">
        <caption>
          <title>ECO ESTRESSE NA SALA DE EMERG&#202;NCIA: DOR TOR&#193;CICA AGUDA</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 style="background-color:#76B4CF">
              <th align="left" valign="middle">Recomenda&#231;&#245;es</th>
              <th align="center" valign="middle">Forca de Recomenda&#231;&#227;o</th>
              <th align="center" valign="middle">Certeza da Evid&#234;ncia</th>
            </tr>
          </thead>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr>
              <td align="left" valign="middle">Na dor tor&#225;cica aguda em pacientes de risco intermedi&#225;rio (sem anormalidades no ECG e/ou biomarcadores negativos).<break/> Em pacientes com suspeita de dor tor&#225;cica anginosa e com troponina negativa ou discretamente aumentada, na estratifica&#231;&#227;o do risco do paciente, desde que na aus&#234;ncia de altera&#231;&#245;es eletrocardiogr&#225;ficas ou recorr&#234;ncia de dor.</td>
              <td align="center" valign="middle" style="background-color:#00CC66">
                <bold>FORTE</bold>
              </td>
              <td align="center" valign="middle" style="background-color:#9CC2E5">
                <bold>MODERADA</bold>
              </td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <table-wrap id="t28">
        <caption>
          <title>ECO ESTRESSE NA DOEN&#199;A VALVAR</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 style="background-color:#76B4CF">
              <th align="left" valign="middle">Recomenda&#231;&#245;es</th>
              <th align="center" valign="middle">Forca de Recomenda&#231;&#227;o</th>
              <th align="center" valign="middle">Certeza da Evid&#234;ncia</th>
            </tr>
          </thead>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr>
              <td align="left" valign="middle">Ecocardiograma de estresse com dobutamina em baixa dose em pacientes portadores de estenose valvar a&#243;rtica baixo fluxo baixo gradiente (cl&#225;ssica) com FE&lt;50%, para confirmar a gravidade da estenose.<break/> Ecocardiograma de estresse com exerc&#237;cio pode ser utilizado para avaliar a repercuss&#227;o hemodin&#226;mica da les&#227;o valvar em pacientes que apresentam discrep&#226;ncia entre os sintomas e os dados do ecocardiograma de repouso.</td>
              <td align="center" valign="middle" style="background-color:#00CC66">
                <bold>FORTE</bold>
              </td>
              <td align="center" valign="middle" style="background-color:#00B0F0">
                <bold>ALTA</bold>
              </td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <table-wrap id="t29">
        <caption>
          <title>ECO ESTRESSE DIAST&#211;LICO</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 style="background-color:#76B4CF">
              <th align="left" valign="middle">Recomenda&#231;&#245;es</th>
              <th align="center" valign="middle">Forca de Recomenda&#231;&#227;o</th>
              <th align="center" valign="middle">Certeza da Evid&#234;ncia</th>
            </tr>
          </thead>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr>
              <td align="left" valign="middle">Eco de estresse sob exerc&#237;cio prefer&#234;ncialmente em ciclomaca ou em esteira ergom&#233;trica, para pacientes com dispneia a esclarecer, e: <break/>Disfun&#231;&#227;o diast&#243;lica grau 1;<break/> Escore H<sub>2</sub>FPEF ou HFA-PEFF com pontua&#231;&#227;o intermedi&#225;ria (2&#8211;5 pontos e 2&#8211;4 pontos respectivamente).</td>
              <td align="center" valign="middle" style="background-color:#00CC66">
                <bold>FORTE</bold>
              </td>
              <td align="center" valign="middle" style="background-color:#00B0F0">
                <bold>ALTA</bold>
              </td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <table-wrap id="t30">
        <caption>
          <title>ECO ESTRESSE COM AGENTES DE REALCE ULTRASSONOGR&#193;FICO (ARUS) PARA AN&#193;LISE DA BORDA ENDOC&#193;RDICA</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 style="background-color:#76B4CF">
              <th align="left" valign="middle">Recomenda&#231;&#245;es</th>
              <th align="center" valign="middle">Forca de Recomenda&#231;&#227;o</th>
              <th align="center" valign="middle">Certeza da Evid&#234;ncia</th>
            </tr>
          </thead>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr>
              <td align="left" valign="middle">Eco de estresse com ARU, quando dois ou mais segmentos mioc&#225;rdicos cont&#237;guos n&#227;o s&#227;o visualizados (no plano apical), para melhorar a acur&#225;cia diagn&#243;stica.</td>
              <td align="center" valign="middle" style="background-color:#00CC66">
                <bold>FORTE</bold>
              </td>
              <td align="center" valign="middle" style="background-color:#00B0F0">
                <bold>ALTA</bold>
              </td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <table-wrap id="t31">
        <caption>
          <title>ECO ESTRESSE COM AGENTES DE REALCE ULTRASSONOGR&#193;FICO (ARUS) PARA AN&#193;LISE DA PERFUS&#195;O MIOC&#193;RDICA</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 style="background-color:#76B4CF">
              <th align="left" valign="middle">Recomenda&#231;&#245;es</th>
              <th align="center" valign="middle">Forca de Recomenda&#231;&#227;o</th>
              <th align="center" valign="middle">Certeza da Evid&#234;ncia</th>
            </tr>
          </thead>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr>
              <td align="left" valign="middle">Avalia&#231;&#227;o de perfus&#227;o mioc&#225;rdica para aumento da acur&#225;cia na identifica&#231;&#227;o da DAC obstrutiva e para a an&#225;lise de viabilidade mioc&#225;rdica.</td>
              <td align="center" valign="middle" style="background-color:#FFFF99">
                <bold>FRACA</bold>
              </td>
              <td align="center" valign="middle" style="background-color:#00B0F0">
                <bold>ALTA</bold>
              </td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <table-wrap id="t32">
        <caption>
          <title>ECO ESTRESSE EM PEDIATRIA</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 style="background-color:#76B4CF">
              <th align="left" valign="middle"/>
              <th align="center" valign="middle">Forca de Recomenda&#231;&#227;o</th>
              <th align="center" valign="middle">Certeza da Evid&#234;ncia</th>
            </tr>
          </thead>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr>
              <td align="left" valign="middle">Parece vantajoso ao observar estenose ou regurgita&#231;&#227;o valvar, obstru&#231;&#227;o din&#226;mica da via de sa&#237;da do ventr&#237;culo esquerdo e direito.<break/> Hipertens&#227;o arterial pulmonar.<break/> Avalia&#231;&#227;o de isquemia mioc&#225;rdica (OAAC, OACE, doen&#231;a de Kawasaki, em pacientes submetidos a cirurgia card&#237;aca com manipula&#231;&#227;o de coron&#225;rias como em p&#243;s operat&#243;rio de Jatene).<break/> P&#243;s transplante para avaliar isquemia</td>
              <td align="center" valign="middle" style="background-color:#FFFF99">
                <bold>FRACA</bold>
              </td>
              <td align="center" valign="middle" style="background-color:#DEEAF6">
                <bold>BAIXA</bold>
              </td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN14">
            <p>OAAC: Origem an&#244;mala a&#243;rtica das art&#233;rias coron&#225;rias; OACE: Origem an&#244;mala da coron&#225;ria esquerda do tronco pulmonar.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="other" id="fn1">
        <label>Realiza&#231;&#227;o:</label>
        <p>Departamento de Imagem Cardiovascular da Sociedade Brasileira de Cardiologia (DIC/SBC), Sociedade Interamericana de Imagem Cardiovascular (SISIAC)</p>
      </fn>
      <fn fn-type="other" id="fn2">
        <label>Conselho de Normatiza&#231;&#245;es e Diretrizes respons&#225;vel:</label>
        <p>Humberto Graner Moreira (Coordenador), F&#233;lix Jos&#233; Alvarez Ramires, Helena Cramer Veiga Rey, Jos&#233; Augusto Soares Barreto Filho, Nadine Oliveira Clausell.</p>
      </fn>
      <fn fn-type="other" id="fn3">
        <label>Nota:</label>
        <p>Estas diretrizes se prestam a informar e n&#227;o a substituir o julgamento cl&#237;nico do m&#233;dico que, em &#250;ltima an&#225;lise, deve determinar o tratamento apropriado para seus pacientes.</p>
      </fn>
    </fn-group>
    <sec sec-type="data-availability" specific-use="data-in-article">
      <title>Disponibilidade de Dados:</title>
      <p>os conte&#250;dos subjacentes ao texto do Posicionamento est&#227;o contidos no manuscrito.</p>
    </sec>
    <glossary>
      <def-list>
        <title>Lista de abreviaturas e siglas</title>
        <def-item>
          <term id="G1">ADA</term>
          <def>
            <p>Art&#233;ria descendente anterior</p>
          </def>
        </def-item>
        <def-item>
          <term id="G2">ARUS</term>
          <def>
            <p>Agente de realce ultrassonogr&#225;fico</p>
          </def>
        </def-item>
        <def-item>
          <term id="G3">ATC</term>
          <def>
            <p>Angiotomografia das coron&#225;rias</p>
          </def>
        </def-item>
        <def-item>
          <term id="G4">BAV</term>
          <def>
            <p>Bloqueio atrioventricular</p>
          </def>
        </def-item>
        <def-item>
          <term id="G5">BCRE</term>
          <def>
            <p>Bloqueio completo do ramo esquerdo</p>
          </def>
        </def-item>
        <def-item>
          <term id="G6">BRD</term>
          <def>
            <p>Bloqueio do ramo direito</p>
          </def>
        </def-item>
        <def-item>
          <term id="G7">BRE</term>
          <def>
            <p>Bloqueio de ramo esquerdo</p>
          </def>
        </def-item>
        <def-item>
          <term id="G8">CCD</term>
          <def>
            <p>Cateterismo card&#237;aco direito</p>
          </def>
        </def-item>
        <def-item>
          <term id="G9">CCDC</term>
          <def>
            <p>Cardiopatia cr&#244;nica da doen&#231;a de Chagas</p>
          </def>
        </def-item>
        <def-item>
          <term id="G10">CMD</term>
          <def>
            <p>Cardiomiopatia dilatada</p>
          </def>
        </def-item>
        <def-item>
          <term id="G11">CMH</term>
          <def>
            <p>Cardiomiopatia hipertr&#243;fica</p>
          </def>
        </def-item>
        <def-item>
          <term id="G12">CV</term>
          <def>
            <p>Cardiovascular</p>
          </def>
        </def-item>
        <def-item>
          <term id="G13">DA</term>
          <def>
            <p>Doen&#231;a arterial</p>
          </def>
        </def-item>
        <def-item>
          <term id="G14">DAC</term>
          <def>
            <p>Doen&#231;a arterial coronariana</p>
          </def>
        </def-item>
        <def-item>
          <term id="G15">DC</term>
          <def>
            <p>D&#233;bito card&#237;aco</p>
          </def>
        </def-item>
        <def-item>
          <term id="G16">DCV</term>
          <def>
            <p>Doen&#231;a cardiovascular</p>
          </def>
        </def-item>
        <def-item>
          <term id="G17">DVM</term>
          <def>
            <p>Doen&#231;a valvar mitral</p>
          </def>
        </def-item>
        <def-item>
          <term id="G18">EAO</term>
          <def>
            <p>Estenose a&#243;rtica</p>
          </def>
        </def-item>
        <def-item>
          <term id="G19">ECG</term>
          <def>
            <p>Eletrocardiograma</p>
          </def>
        </def-item>
        <def-item>
          <term id="G20">EED</term>
          <def>
            <p>Ecocardiografia de estresse farmacol&#243;gico com dobutamina</p>
          </def>
        </def-item>
        <def-item>
          <term id="G21">EEDiast</term>
          <def>
            <p>Ecocardiografia de estresse diast&#243;lico</p>
          </def>
        </def-item>
        <def-item>
          <term id="G22">EEDIP</term>
          <def>
            <p>Ecocardiografia de estresse com dipiridamol</p>
          </def>
        </def-item>
        <def-item>
          <term id="G23">EEE</term>
          <def>
            <p>Ecocardiografia de estresse de esfor&#231;o</p>
          </def>
        </def-item>
        <def-item>
          <term id="G24">EEF</term>
          <def>
            <p>Ecocardiografia de estresse f&#237;sico</p>
          </def>
        </def-item>
        <def-item>
          <term id="G25">EM</term>
          <def>
            <p>Estenose mitral</p>
          </def>
        </def-item>
        <def-item>
          <term id="G26">ETT</term>
          <def>
            <p>Ecocardiografia transtor&#225;cica</p>
          </def>
        </def-item>
        <def-item>
          <term id="G27">FA</term>
          <def>
            <p>Fibrila&#231;&#227;o atrial</p>
          </def>
        </def-item>
        <def-item>
          <term id="G28">FC</term>
          <def>
            <p>Frequ&#234;ncia card&#237;aca</p>
          </def>
        </def-item>
        <def-item>
          <term id="G29">FD</term>
          <def>
            <p>Fun&#231;&#227;o diast&#243;lica</p>
          </def>
        </def-item>
        <def-item>
          <term id="G30">HP</term>
          <def>
            <p>Hipertens&#227;o pulmonar</p>
          </def>
        </def-item>
        <def-item>
          <term id="G31">IAO</term>
          <def>
            <p>Insufici&#234;ncia a&#243;rtica</p>
          </def>
        </def-item>
        <def-item>
          <term id="G32">IC</term>
          <def>
            <p>Insufici&#234;ncia card&#237;aca</p>
          </def>
        </def-item>
        <def-item>
          <term id="G33">ICFEp</term>
          <def>
            <p>Insufici&#234;ncia card&#237;aca com fra&#231;&#227;o de eje&#231;&#227;o preservada</p>
          </def>
        </def-item>
        <def-item>
          <term id="G34">IM</term>
          <def>
            <p>&#205;ndice mec&#226;nico</p>
          </def>
        </def-item>
        <def-item>
          <term id="G35">LFLG</term>
          <def>
            <p>
              <italic>low-flow, low-gradient</italic>
            </p>
          </def>
        </def-item>
        <def-item>
          <term id="G36">MACE</term>
          <def>
            <p>eventos cardiovasculares adversos maiores (<italic>major adverse cardiovascular events</italic>)</p>
          </def>
        </def-item>
        <def-item>
          <term id="G37">MCPD</term>
          <def>
            <p>Marca-passo definitivo</p>
          </def>
        </def-item>
        <def-item>
          <term id="G38">PA</term>
          <def>
            <p>Press&#227;o arterial</p>
          </def>
        </def-item>
        <def-item>
          <term id="G39">PAD</term>
          <def>
            <p>Press&#227;o arterial diast&#243;lica</p>
          </def>
        </def-item>
        <def-item>
          <term id="G40">PAS</term>
          <def>
            <p>Press&#227;o arterial sist&#243;lica</p>
          </def>
        </def-item>
        <def-item>
          <term id="G41">PEG</term>
          <def>
            <p>Polietilenoglicol</p>
          </def>
        </def-item>
        <def-item>
          <term id="G42">PET</term>
          <def>
            <p>Tomografia por emiss&#227;o de p&#243;sitrons (<italic>positron emission tomography</italic>)</p>
          </def>
        </def-item>
        <def-item>
          <term id="G43">PEVE</term>
          <def>
            <p>Press&#227;o de enchimento do ventr&#237;culo esquerdo</p>
          </def>
        </def-item>
        <def-item>
          <term id="G44">PM</term>
          <def>
            <p>Perfus&#227;o mioc&#225;rdica</p>
          </def>
        </def-item>
        <def-item>
          <term id="G45">PSAP</term>
          <def>
            <p>Press&#227;o sist&#243;lica da art&#233;ria pulmonar</p>
          </def>
        </def-item>
        <def-item>
          <term id="G46">RC</term>
          <def>
            <p>Reserva contr&#225;til</p>
          </def>
        </def-item>
        <def-item>
          <term id="G47">RFC</term>
          <def>
            <p>Reserva de fluxo coronariano</p>
          </def>
        </def-item>
        <def-item>
          <term id="G48">RM</term>
          <def>
            <p>Reserva mioc&#225;rdica</p>
          </def>
        </def-item>
        <def-item>
          <term id="G49">RNM-C</term>
          <def>
            <p>Resson&#226;ncia magn&#233;tica do cora&#231;&#227;o</p>
          </def>
        </def-item>
        <def-item>
          <term id="G50">RT</term>
          <def>
            <p>Radioterapia</p>
          </def>
        </def-item>
        <def-item>
          <term id="G51">SCA</term>
          <def>
            <p>S&#237;ndrome coronariana aguda</p>
          </def>
        </def-item>
        <def-item>
          <term id="G52">SLG</term>
          <def>
            <p><italic>Strain</italic> longitudinal global</p>
          </def>
        </def-item>
        <def-item>
          <term id="G53">SPECT</term>
          <def>
            <p>Tomografia computadorizada por emiss&#227;o de f&#243;ton &#250;nico (<italic>single-photon emission computed tomography</italic>)</p>
          </def>
        </def-item>
        <def-item>
          <term id="G54">SPI</term>
          <def>
            <p>&#205;ndice p&#243;s sist&#243;lico</p>
          </def>
        </def-item>
        <def-item>
          <term id="G55">SR</term>
          <def>
            <p>Strain rate</p>
          </def>
        </def-item>
        <def-item>
          <term id="G56">VD</term>
          <def>
            <p>Ventr&#237;culo direito</p>
          </def>
        </def-item>
        <def-item>
          <term id="G57">VE</term>
          <def>
            <p>Ventr&#237;culo esquerdo</p>
          </def>
        </def-item>
        <def-item>
          <term id="G58">VSF</term>
          <def>
            <p>Volume sist&#243;lico final</p>
          </def>
        </def-item>
        <def-item>
          <term id="G59">VSVE</term>
          <def>
            <p>Via de sa&#237;da do ventr&#237;culo esquerdo</p>
          </def>
        </def-item>
        <def-item>
          <term id="G60">WMSI</term>
          <def>
            <p>Escore de motilidade parietal (<italic>wall motion score index</italic>)</p>
          </def>
        </def-item>
      </def-list>
    </glossary>
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  <sub-article article-type="translation" id="S1" xml:lang="en">
    <front-stub>
      <article-id pub-id-type="doi">10.36660/abc.20260223i</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Guidelines</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Guideline on Stress Echocardiography &#8211; 2026</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-9291-1308</contrib-id>
          <name>
            <surname>Camarozano</surname>
            <given-names>Ana Cristina</given-names>
          </name>
          <xref ref-type="aff" rid="aff50">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-4884-0223</contrib-id>
          <name>
            <surname>Spina</surname>
            <given-names>Salvador Vicente</given-names>
          </name>
          <xref ref-type="aff" rid="aff51">
            <sup>2</sup>
          </xref>
          <xref ref-type="aff" rid="aff52">
            <sup>3</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-6737-4187</contrib-id>
          <name>
            <surname>Souza</surname>
            <given-names>Jos&#233; Roberto Matos</given-names>
          </name>
          <xref ref-type="aff" rid="aff53">
            <sup>4</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-8809-8783</contrib-id>
          <name>
            <surname>Melo</surname>
            <given-names>Marcelo Dantas Tavares de</given-names>
          </name>
          <xref ref-type="aff" rid="aff54">
            <sup>5</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-9131-0439</contrib-id>
          <name>
            <surname>Frota</surname>
            <given-names>Daniela do Carmo Rassi</given-names>
          </name>
          <xref ref-type="aff" rid="aff55">
            <sup>6</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-0711-7995</contrib-id>
          <name>
            <surname>Barberato</surname>
            <given-names>Silvio Henrique</given-names>
          </name>
          <xref ref-type="aff" rid="aff56">
            <sup>7</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-8760-2052</contrib-id>
          <name>
            <surname>Guimar&#227;es</surname>
            <given-names>Fabio Villa&#231;a</given-names>
            <suffix>Filho</suffix>
          </name>
          <xref ref-type="aff" rid="aff57">
            <sup>8</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-5115-8495</contrib-id>
          <name>
            <surname>Acquatella</surname>
            <given-names>Harry</given-names>
          </name>
          <xref ref-type="aff" rid="aff58">
            <sup>9</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gimenes</surname>
            <given-names>Vera M&#225;rcia Lopes</given-names>
          </name>
          <xref ref-type="aff" rid="aff59">
            <sup>10</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-5804-9075</contrib-id>
          <name>
            <surname>Lowenstein</surname>
            <given-names>Jorge Alfredo</given-names>
          </name>
          <xref ref-type="aff" rid="aff60">
            <sup>11</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-3862-7672</contrib-id>
          <name>
            <surname>Pignatelli</surname>
            <given-names>Ricardo H</given-names>
          </name>
          <xref ref-type="aff" rid="aff61">
            <sup>12</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2214-203X</contrib-id>
          <name>
            <surname>Castillo</surname>
            <given-names>Jos&#233; Maria Del</given-names>
          </name>
          <xref ref-type="aff" rid="aff62">
            <sup>13</sup>
          </xref>
          <xref ref-type="aff" rid="aff63">
            <sup>14</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-4325-0590</contrib-id>
          <name>
            <surname>Oliveira</surname>
            <given-names>Joselina Luiza Menezes</given-names>
          </name>
          <xref ref-type="aff" rid="aff64">
            <sup>15</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-6650-1292</contrib-id>
          <name>
            <surname>Abreu</surname>
            <given-names>Jos&#233; Sebasti&#227;o de</given-names>
          </name>
          <xref ref-type="aff" rid="aff65">
            <sup>16</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-1909-2753</contrib-id>
          <name>
            <surname>Pretto</surname>
            <given-names>Jos&#233; Luis de Castro e Silva</given-names>
          </name>
          <xref ref-type="aff" rid="aff66">
            <sup>17</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0009-0004-8772-7954</contrib-id>
          <name>
            <surname>Shehadeh</surname>
            <given-names>Issam</given-names>
          </name>
          <xref ref-type="aff" rid="aff67">
            <sup>18</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-7046-8707</contrib-id>
          <name>
            <surname>Felix</surname>
            <given-names>Alex dos Santos</given-names>
          </name>
          <xref ref-type="aff" rid="aff68">
            <sup>19</sup>
          </xref>
          <xref ref-type="aff" rid="aff69">
            <sup>20</sup>
          </xref>
          <xref ref-type="aff" rid="aff70">
            <sup>21</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Andrade</surname>
            <given-names>Mercedes Maldonado</given-names>
          </name>
          <xref ref-type="aff" rid="aff71">
            <sup>22</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-0439-9808</contrib-id>
          <name>
            <surname>Sousa</surname>
            <given-names>Ant&#244;nio Carlos Sobral</given-names>
          </name>
          <xref ref-type="aff" rid="aff64">
            <sup>15</sup>
          </xref>
          <xref ref-type="aff" rid="aff72">
            <sup>23</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2634-4632</contrib-id>
          <name>
            <surname>Otto</surname>
            <given-names>Maria Estef&#226;nia Bosco</given-names>
          </name>
          <xref ref-type="aff" rid="aff73">
            <sup>24</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-0056-4378</contrib-id>
          <name>
            <surname>Vilela</surname>
            <given-names>Andrea de Andrade</given-names>
          </name>
          <xref ref-type="aff" rid="aff71">
            <sup>22</sup>
          </xref>
          <xref ref-type="aff" rid="aff74">
            <sup>25</sup>
          </xref>
          <xref ref-type="aff" rid="aff75">
            <sup>26</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2864-8701</contrib-id>
          <name>
            <surname>Fajardo</surname>
            <given-names>Pedro Gutierrez</given-names>
          </name>
          <xref ref-type="aff" rid="aff76">
            <sup>27</sup>
          </xref>
          <xref ref-type="aff" rid="aff77">
            <sup>28</sup>
          </xref>
          <xref ref-type="aff" rid="aff78">
            <sup>29</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-5005-5005</contrib-id>
          <name>
            <surname>Baroncini</surname>
            <given-names>Liz Andr&#233;a Villela</given-names>
          </name>
          <xref ref-type="aff" rid="aff79">
            <sup>30</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Machado</surname>
            <given-names>Cristiano Vieira</given-names>
          </name>
          <xref ref-type="aff" rid="aff80">
            <sup>31</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0009-0006-1768-3380</contrib-id>
          <name>
            <surname>Moreira</surname>
            <given-names>F&#225;bio Ca&#241;ellas</given-names>
          </name>
          <xref ref-type="aff" rid="aff81">
            <sup>32</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-4018-7346</contrib-id>
          <name>
            <surname>Hern&#225;ndez</surname>
            <given-names>Jos&#233; Mar&#237;a Hern&#225;ndez</given-names>
          </name>
          <xref ref-type="aff" rid="aff82">
            <sup>33</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-0794-7339</contrib-id>
          <name>
            <surname>Alves</surname>
            <given-names>Marco Stephan Lofrano</given-names>
          </name>
          <xref ref-type="aff" rid="aff50">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-5531-9647</contrib-id>
          <name>
            <surname>Morhy</surname>
            <given-names>Samira Saady</given-names>
          </name>
          <xref ref-type="aff" rid="aff74">
            <sup>25</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-6110-2500</contrib-id>
          <name>
            <surname>Lima</surname>
            <given-names>M&#225;rcio Silva Miguel</given-names>
          </name>
          <xref ref-type="aff" rid="aff83">
            <sup>34</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-9083-8269</contrib-id>
          <name>
            <surname>Aguiar</surname>
            <given-names>Miguel Osman Dias</given-names>
          </name>
          <xref ref-type="aff" rid="aff84">
            <sup>35</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-0201-6754</contrib-id>
          <name>
            <surname>Mathias</surname>
            <given-names>Wilson</given-names>
            <suffix>Junior</suffix>
          </name>
          <xref ref-type="aff" rid="aff83">
            <sup>34</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-4551-1096</contrib-id>
          <name>
            <surname>Rocha</surname>
            <given-names>Let&#237;cia dos Santos de Oliveira</given-names>
          </name>
          <xref ref-type="aff" rid="aff85">
            <sup>36</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2462-2010</contrib-id>
          <name>
            <surname>Sbano</surname>
            <given-names>Jo&#227;o C&#233;sar Nunes</given-names>
          </name>
          <xref ref-type="aff" rid="aff83">
            <sup>34</sup>
          </xref>
          <xref ref-type="aff" rid="aff86">
            <sup>37</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-5611-4002</contrib-id>
          <name>
            <surname>Vrandecic</surname>
            <given-names>Barbara Athayde Linhares Martins</given-names>
          </name>
          <xref ref-type="aff" rid="aff87">
            <sup>38</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-1254-6820</contrib-id>
          <name>
            <surname>Roston</surname>
            <given-names>Fabio</given-names>
          </name>
          <xref ref-type="aff" rid="aff88">
            <sup>39</sup>
          </xref>
          <xref ref-type="aff" rid="aff89">
            <sup>40</sup>
          </xref>
          <xref ref-type="aff" rid="aff90">
            <sup>41</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2959-1874</contrib-id>
          <name>
            <surname>Rabischoffsky</surname>
            <given-names>Arnaldo</given-names>
          </name>
          <xref ref-type="aff" rid="aff91">
            <sup>42</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0009-0000-1656-6218</contrib-id>
          <name>
            <surname>Rolim</surname>
            <given-names>Juliana Paix&#227;o Etto</given-names>
          </name>
          <xref ref-type="aff" rid="aff83">
            <sup>34</sup>
          </xref>
          <xref ref-type="aff" rid="aff92">
            <sup>43</sup>
          </xref>
          <xref ref-type="aff" rid="aff93">
            <sup>44</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-9580-4703</contrib-id>
          <name>
            <surname>Silva</surname>
            <given-names>Raphael Aparecido Barreto da</given-names>
          </name>
          <xref ref-type="aff" rid="aff57">
            <sup>8</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-5861-1718</contrib-id>
          <name>
            <surname>Rossi</surname>
            <given-names>Guilherme de</given-names>
          </name>
          <xref ref-type="aff" rid="aff94">
            <sup>45</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0009-0003-4528-4174</contrib-id>
          <name>
            <surname>Staszko</surname>
            <given-names>Kamila Fernanda</given-names>
          </name>
          <xref ref-type="aff" rid="aff95">
            <sup>46</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-3388-5840</contrib-id>
          <name>
            <surname>Britt</surname>
            <given-names>Jolie</given-names>
          </name>
          <xref ref-type="aff" rid="aff96">
            <sup>47</sup>
          </xref>
          <xref ref-type="aff" rid="aff97">
            <sup>48</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Vieira</surname>
            <given-names>Marcelo Luiz Campos</given-names>
          </name>
          <xref ref-type="aff" rid="aff74">
            <sup>25</sup>
          </xref>
          <xref ref-type="aff" rid="aff83">
            <sup>34</sup>
          </xref>
          <xref ref-type="aff" rid="aff98">
            <sup>49</sup>
          </xref>
        </contrib>
        <aff id="aff50">
          <label>1</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">Universidade Federal do Paran&#225;, Curitiba, PR &#8211; Brazil</institution>
        </aff>
        <aff id="aff51">
          <label>2</label>
          <addr-line>
            <named-content content-type="city">Buenos Aires</named-content>
            <named-content content-type="state">BA</named-content>
          </addr-line>
          <country country="AR">Argentina</country>
          <institution content-type="original">Hospital Aeron&#225;utico Central, Buenos Aires, BA &#8211; Argentina</institution>
        </aff>
        <aff id="aff52">
          <label>3</label>
          <addr-line>
            <named-content content-type="city">Ramos Mej&#237;a Pcia</named-content>
            <named-content content-type="state">BA</named-content>
          </addr-line>
          <country country="AR">Argentina</country>
          <institution content-type="original">Centro M&#233;dico Don Bosco, Ramos Mej&#237;a Pcia, BA &#8211; Argentina</institution>
        </aff>
        <aff id="aff53">
          <label>4</label>
          <addr-line>
            <named-content content-type="city">Campinas</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade de Campinas, Campinas, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff54">
          <label>5</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, Jo&#227;o Pessoa, PB &#8211; Brazil</institution>
        </aff>
        <aff id="aff55">
          <label>6</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">Hospital das Clinicas da Universidade Federal de Goi&#225;s, Goi&#226;nia, GO &#8211; Brazil</institution>
        </aff>
        <aff id="aff56">
          <label>7</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;, Curitiba, PR &#8211; Brazil</institution>
        </aff>
        <aff id="aff57">
          <label>8</label>
          <addr-line>
            <named-content content-type="city">Marilia</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 de Mar&#237;lia, Marilia, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff58">
          <label>9</label>
          <addr-line>
            <named-content content-type="city">Caracas</named-content>
            <named-content content-type="state">CCS</named-content>
          </addr-line>
          <country country="VE">Venezuela</country>
          <institution content-type="original">Centro Medico de Caracas, Caracas, CCS &#8211; Venezuela</institution>
        </aff>
        <aff id="aff59">
          <label>10</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 do Cora&#231;&#227;o, S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff60">
          <label>11</label>
          <addr-line>
            <named-content content-type="city">Buenos Aires</named-content>
            <named-content content-type="state">BA</named-content>
          </addr-line>
          <country country="AR">Argentina</country>
          <institution content-type="original">Cardiodiagn&#243;stico, Investigaciones Medicas Buenos Aires, Buenos Aires, BA &#8211; Argentina</institution>
        </aff>
        <aff id="aff61">
          <label>12</label>
          <addr-line>
            <named-content content-type="city">Houston</named-content>
            <named-content content-type="state">TX</named-content>
          </addr-line>
          <country country="US">United States of America</country>
          <institution content-type="original">Texas Children's Hospital- Baylor College of Medicine, Houston, TX &#8211; United States of America</institution>
        </aff>
        <aff id="aff62">
          <label>13</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">Escola de Ecografia de Pernambuco, Recife, PE &#8211; Brazil</institution>
        </aff>
        <aff id="aff63">
          <label>14</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 Cat&#243;lica de Pernambuco, Recife, PE &#8211; Brazil</institution>
        </aff>
        <aff id="aff64">
          <label>15</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, Aracaju, SE &#8211; Brazil</institution>
        </aff>
        <aff id="aff65">
          <label>16</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">Clinicardio de Fortaleza e Cardioexata, Fortaleza, CE &#8211; Brazil</institution>
        </aff>
        <aff id="aff66">
          <label>17</label>
          <addr-line>
            <named-content content-type="city">Passo Fundo</named-content>
            <named-content content-type="state">RS</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Hospital S&#227;o Vicente de Paulo, Passo Fundo, RS &#8211; Brazil</institution>
        </aff>
        <aff id="aff67">
          <label>18</label>
          <addr-line>
            <named-content content-type="city">Esteio</named-content>
            <named-content content-type="state">RS</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Cl&#237;nica Cardiovision, Esteio, RS &#8211; Brazil</institution>
        </aff>
        <aff id="aff68">
          <label>19</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">Instituto Nacional de Cardiologia, Rio de Janeiro, RJ &#8211; Brazil</institution>
        </aff>
        <aff id="aff69">
          <label>20</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">Diagn&#243;sticos da Am&#233;rica S.A. (DASA-RJ), Rio de Janeiro, RJ &#8211; Brazil</institution>
        </aff>
        <aff id="aff70">
          <label>21</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">Complexo Hospitalar Americas, Rio de Janeiro, RJ &#8211; Brazil</institution>
        </aff>
        <aff id="aff71">
          <label>22</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="aff72">
          <label>23</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, Rede D'Or de Aracaju, Aracaju, SE &#8211; Brazil</institution>
        </aff>
        <aff id="aff73">
          <label>24</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, Bras&#237;lia, DF &#8211; Brazil</institution>
        </aff>
        <aff id="aff74">
          <label>25</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="aff75">
          <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">Hospital Lefort Morumbi, S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff76">
          <label>27</label>
          <addr-line>
            <named-content content-type="city">Guadalajara</named-content>
            <named-content content-type="state">JAL</named-content>
          </addr-line>
          <country country="MX">Mexico</country>
          <institution content-type="original">Hospital de Especialidades San Francisco de Asis, Guadalajara, JAL &#8211; Mexico</institution>
        </aff>
        <aff id="aff77">
          <label>28</label>
          <addr-line>
            <named-content content-type="city">Guadalajara</named-content>
            <named-content content-type="state">JAL</named-content>
          </addr-line>
          <country country="MX">Mexico</country>
          <institution content-type="original">Cardiotest, Guadalajara, JAL &#8211; Mexico</institution>
        </aff>
        <aff id="aff78">
          <label>29</label>
          <addr-line>
            <named-content content-type="city">Guadalajara</named-content>
            <named-content content-type="state">JAL</named-content>
          </addr-line>
          <country country="MX">Mexico</country>
          <institution content-type="original">Laboratorio de Ecocaerdiografia, Guadalajara, JAL &#8211; Mexico</institution>
        </aff>
        <aff id="aff79">
          <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">Hospital Nossa Senhora Das Gracas, Curitiba, PR &#8211; Brazil</institution>
        </aff>
        <aff id="aff80">
          <label>31</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">Fleury Medicina e Sa&#250;de, Grupo Fleury, S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff81">
          <label>32</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">Santa Casa De Miseric&#243;rdia De Porto Alegre, Porto Alegre, RS &#8211; Brazil</institution>
        </aff>
        <aff id="aff82">
          <label>33</label>
          <addr-line>
            <named-content content-type="city">Monterrey</named-content>
            <named-content content-type="state">NL</named-content>
          </addr-line>
          <country country="MX">Mexico</country>
          <institution content-type="original">Imaging Cardiac Department. Doctors Hospital Auna, Monterrey, NL &#8211; Mexico</institution>
        </aff>
        <aff id="aff83">
          <label>34</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 do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff84">
          <label>35</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 Benefic&#234;ncia Portuguesa de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff85">
          <label>36</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">Hospital Pequeno Pr&#237;ncipe, Curitiba, PR &#8211; Brazil</institution>
        </aff>
        <aff id="aff86">
          <label>37</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">Grupo Fleury Medicina e Sa&#250;de, S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff87">
          <label>38</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 Biocor/Rede D'or, Belo Horizonte, MG &#8211; Brazil</institution>
        </aff>
        <aff id="aff88">
          <label>39</label>
          <addr-line>
            <named-content content-type="city">Londrina</named-content>
            <named-content content-type="state">PR</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Cl&#237;nica Clinicardio, Londrina, PR &#8211; Brazil</institution>
        </aff>
        <aff id="aff89">
          <label>40</label>
          <addr-line>
            <named-content content-type="city">Arapongas</named-content>
            <named-content content-type="state">PR</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Hospital Norte Paranaense HONPAR, Arapongas, PR &#8211; Brazil</institution>
        </aff>
        <aff id="aff90">
          <label>41</label>
          <addr-line>
            <named-content content-type="city">Londrina</named-content>
            <named-content content-type="state">PR</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Grupo Cura (Labimagem e Ultramed), Londrina, PR &#8211; Brazil</institution>
        </aff>
        <aff id="aff91">
          <label>42</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="aff92">
          <label>43</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 S&#237;rio Liban&#234;, S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff93">
          <label>44</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">Alta (Rede Dasa), S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff94">
          <label>45</label>
          <addr-line>
            <named-content content-type="city">Campinas</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Centro Especializado em Cardiologia LTDA, Campinas, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff95">
          <label>46</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">Complexo do Hospital de Cl&#237;nicas da Universidade Federal do Paran&#225; (CHC-UFPR), Curitiba, PR &#8211; Brazil</institution>
        </aff>
        <aff id="aff96">
          <label>47</label>
          <addr-line>
            <named-content content-type="city">Houston</named-content>
            <named-content content-type="state">TX</named-content>
          </addr-line>
          <country country="US">United States of America</country>
          <institution content-type="original">Baylor College of Medicine, Houston, TX &#8211; United States of America</institution>
        </aff>
        <aff id="aff97">
          <label>48</label>
          <addr-line>
            <named-content content-type="city">Houston</named-content>
            <named-content content-type="state">TX</named-content>
          </addr-line>
          <country country="US">United States of America</country>
          <institution content-type="original">Texas Children's Hospital, Houston, TX &#8211; United States of America</institution>
        </aff>
        <aff id="aff98">
          <label>49</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 Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><label>Correspondence:</label> Sociedade Brasileira de Cardiologia &#8211; Av. Marechal C&#226;mara, 360/330 &#8211; Centro &#8211; Rio de Janeiro, Brazil &#8211; Postal Code <postal-code>20020-907</postal-code>. E-mail: <email>diretrizes@cardiol.br</email></corresp>
        <fn fn-type="edited-by">
          <label>Coordinating Editor:</label>
          <p>Ana Cristina Camarozano</p>
        </fn>
        <fn fn-type="edited-by">
          <label>Co-Editors:</label>
          <p>Salvador Spina, Jos&#233; Roberto Mattos de Souza, Marcelo Dantas Tavares de Melo, Daniela do Carmo Rassi Frota, Silvio Henrique Barberato, Marcelo Luiz Campos Vieira</p>
        </fn>
        <fn fn-type="edited-by">
          <label>Reviewing Editor:</label>
          <p>Humberto Graner Moreira.</p>
        </fn>
      </author-notes>
    </front-stub>
    <body>
      <table-wrap id="t33">
        <table frame="hsides" rules="rows">
          <colgroup width="50%">
            <col/>
            <col/>
          </colgroup>
          <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
            <tr>
              <th align="center" valign="middle" colspan="2">Guideline on Stress Echocardiography &#8211; 2026</th>
            </tr>
            <tr>
              <th align="center" valign="middle" colspan="2">The report below lists declarations of interest as reported to the SBC by the experts during the period of the development of these statement, 2025/2026.</th>
            </tr>
            <tr>
              <th align="left" valign="middle">Expert</th>
              <th align="center" valign="middle">Type of relationship with industry</th>
            </tr>
          </thead>
          <tbody style="border-bottom: thin solid; border-color: #000000">
            <tr>
              <td align="left" valign="middle">Alex dos Santos Felix</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Ana Cristina Camarozano</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Andrea de Andrade Vilela</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Ant&#244;nio Carlos Sobral Sousa</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Arnaldo Rabischoffsky</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Barbara Athayde Linhares Martins Vrandecic</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Cristiano Vieira Machado</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Daniela do Carmo Rassi Frota</td>
              <td align="left" valign="middle">Financial declaration<break/> A - Economically relevant payments of any kind made to (i) you, (ii) your spouse/partner or any other person living with you, (iii) any legal person in which any of these is either a direct or indirect controlling owner, business partner, shareholder or participant; any payments received for lectures, lessons, training instruction, compensation, fees paid for participation in advisory boards, investigative boards or other committees, etc. from the brazilian or international pharmaceutical, orthosis, prosthesis, equipment and implants industry: <break/>- AstraZeneca Brazil Ltda: Forxiga.</td>
            </tr>
            <tr>
              <td align="left" valign="middle">F&#225;bio Ca&#241;ellas Moreira</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Fabio Roston</td>
              <td align="left" valign="middle">Financial declaration<break/> A - Economically relevant payments of any kind made to (i) you, (ii) your spouse/partner or any other person living with you, (iii) any legal person in which any of these is either a direct or indirect controlling owner, business partner, shareholder or participant; any payments received for lectures, lessons, training instruction, compensation, fees paid for participation in advisory boards, investigative boards or other committees, etc. from the brazilian or international pharmaceutical, orthosis, prosthesis, equipment and implants industry: <break/>- Boston Scientific &#8211; Proctorship in left atrial appendage occlusion..</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Fabio Villaca Guimar&#227;es filho</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Guilherme De Rossi</td>
              <td align="left" valign="middle">Other relationships <break/>Any economically relevant equity interest in companies in the healthcare or education industry or in any companies competing with or supplying to SBC:<break/> - Health area.</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Harry Acquatella</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Issam Shehadeh</td>
              <td align="left" valign="middle">Financial declaration<break/> A - Economically relevant payments of any kind made to (i) you, (ii) your spouse/partner or any other person living with you, (iii) any legal person in which any of these is either a direct or indirect controlling owner, business partner, shareholder or participant; any payments received for lectures, lessons, training instruction, compensation, fees paid for participation in advisory boards, investigative boards or other committees, etc. from the brazilian or international pharmaceutical, orthosis, prosthesis, equipment and implants industry: <break/>- GE Healthcare: Hands-on training in stress echocardiography.<break/> Other relationships <break/>Funding of continuing medical education activities, including travel, accommodation and registration in conferences and courses, from the brazilian or international pharmaceutical, orthosis, prosthesis, equipment and implants industry: <break/>-Torrent: Cardiology; Medley Sanofi: Zinpass Eze.</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Jo&#227;o Cesar Nunes Sbano</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Jolie Britt</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Jorge Alfredo Lowenstein</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Jos&#233; Luis de Castro e Silva Pretto</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Jos&#233; Maria Del Castillo</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Jos&#233; Mar&#237;a Hern&#225;ndez Hern&#225;ndez</td>
              <td align="left" valign="middle">Other relationships <break/>Funding of continuing medical education activities, including travel, accommodation and registration in conferences and courses, from the brazilian or international pharmaceutical, orthosis, prosthesis, equipment and implants industry: <break/>- Vitalmex: LVAD &#8211; Vitacor.<break/> Employment relationship with the brazilian or international pharmaceutical, orthosis, prosthesis, equipment and implants industry, as well as any employment relationship with health insurance companies or medical audit companies (including part-time jobs) in the year to which your declaration refers:<break/> - Vitalmex: LVAD &#8211; Vitacor.</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Jos&#233; Roberto Matos Souza</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Jos&#233; Sebasti&#227;o de Abreu</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Joselina Luzia Menezes Oliveira</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Juliana Paix&#227;o Etto Rolim</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Kamila Fernanda Staszko</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Let&#237;cia dos Santos de Oliveira Rocha</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Liz Andr&#233;a Villela Baroncini</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Marcelo dantas tavares de melo</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Marcelo Luiz Campos Vieira</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">M&#225;rcio Silva Miguel Lima</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Marco Stephan Lofrano Alves</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Maria Estef&#226;nia Bosco Otto</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Mercedes Maldonado Andrade</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Miguel Osman Dias Aguiar</td>
              <td align="left" valign="middle">Other relationships <break/>Any economically relevant equity interest in companies in the healthcare or education industry or in any companies competing with or supplying to SBC:<break/> - Health area.</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Pedro Gutierrez-Fajardo</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Raphael Aparecido Barreto da Silva</td>
              <td align="left" valign="middle">Financial declaration<break/> B - Research funding under your direct/personal responsibility (directed to the department or institution) from the brazilian or international pharmaceutical, orthosis, prosthesis, equipment and implants industry: <break/>- Lilly: obesity, lipoprotein(a); Amgen: heart failure, lipoprotein(a), coronary artery disease; Sanofi: atrial fibrillation; Vertex: renal failure; Boehringer: heart failure; AstraZeneca: dyslipidemia.</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Ricardo H Pignatelli</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Salvador Vicente Spina</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Samira Saady Morhy</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Silvio Henrique Barberato</td>
              <td align="left" valign="middle">Financial declaration<break/> A - Economically relevant payments of any kind made to (i) you, (ii) your spouse/partner or any other person living with you, (iii) any legal person in which any of these is either a direct or indirect controlling owner, business partner, shareholder or participant; any payments received for lectures, lessons, training instruction, compensation, fees paid for participation in advisory boards, investigative boards or other committees, etc. from the brazilian or international pharmaceutical, orthosis, prosthesis, equipment and implants industry: <break/>- Pfizer: Amyloidosis; AstraZeneca: HFpEF.<break/> Other relationships <break/>Funding of continuing medical education activities, including travel, accommodation and registration in conferences and courses, from the brazilian or international pharmaceutical, orthosis, prosthesis, equipment and implants industry: <break/>- Pfizer: Amyloidosis.</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Vera Marcia Lopes Gimenes</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
            <tr>
              <td align="left" valign="middle">Wilson Mathias Junior</td>
              <td align="left" valign="middle">Nothing to be declared</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <sec>
        <title>Table of contents</title>
        <list list-type="simple">
          <list-item>
            <p><bold>1. The Role of Resting Echocardiography Performed at the Time of Physical or Pharmacological Stress Echocardiography</bold> 9</p>
          </list-item>
          <list-item>
            <p><bold>2. The Evolution of Stress Echocardiography: from Inception to the Present Day</bold> 9</p>
          </list-item>
          <list-item>
            <p><bold>3. Ischemia-Inducing Methods</bold> 9</p>
            <list list-type="simple">
              <list-item>
                <p><bold>3.1. Exercise Stress Echocardiography (Bicycle, Treadmill, or Recumbent Bicycle/Echo Couch)</bold> 10</p>
              </list-item>
              <list-item>
                <p><bold>3.2. Pharmacological Stress Echocardiography</bold> 10</p>
              </list-item>
              <list-item>
                <p><bold>3.3. Stress Echocardiography in Coronary Spasm Provocative Testing</bold> 10</p>
              </list-item>
              <list-item>
                <p><bold>3.4. Pacing Stress Echocardiography</bold> 11</p>
              </list-item>
            </list>
          </list-item>
          <list-item>
            <p><bold>4. Exercise Stress Echocardiography (Treadmill, Cycle Ergometer, or Reclining Ergometer/Echo Couch)</bold> 11</p>
          </list-item>
          <list-item>
            <p><bold>5. Dobutamine Stress Echocardiography in the Assessment of Myocardial Ischemia</bold> 13</p>
            <list list-type="simple">
              <list-item>
                <p><bold>5.1. Dobutamine Stress Echocardiography Protocol</bold> 13</p>
              </list-item>
              <list-item>
                <p><bold>5.2. Type of Myocardial Response</bold> 15</p>
              </list-item>
              <list-item>
                <p><bold>5.3. Assessment During DSE and in Recovery</bold> 17</p>
              </list-item>
              <list-item>
                <p><bold>5.4. Transient Ischemic Dilatation of the Left Ventricle</bold> 19</p>
              </list-item>
              <list-item>
                <p><bold>5.5. Comparison with Other Imaging Modalities</bold> 19</p>
              </list-item>
              <list-item>
                <p><bold>5.6. Value of a Negative DSE</bold> 19</p>
              </list-item>
              <list-item>
                <p><bold>5.7. Complications of DSE</bold> 19</p>
              </list-item>
            </list>
          </list-item>
          <list-item>
            <p><bold>6. Dipyridamole Stress Echocardiography</bold> 20</p>
            <list list-type="simple">
              <list-item>
                <p><bold>6.1. Protocols</bold> 20</p>
              </list-item>
              <list-item>
                <p><bold>6.2. Adverse Effects</bold> 20</p>
              </list-item>
              <list-item>
                <p><bold>6.3. Contraindications</bold> 20</p>
              </list-item>
              <list-item>
                <p><bold>6.4. Coronary Flow Reserve</bold> 21</p>
              </list-item>
              <list-item>
                <p><bold>6.5. Accuracy</bold> 22</p>
              </list-item>
            </list>
          </list-item>
          <list-item>
            <p><bold>7. Adenosine or Regadenoson Stress Echocardiography</bold> 22</p>
            <list list-type="simple">
              <list-item>
                <p><bold>7.1. Use During Stress Echocardiography</bold> 22</p>
                <list list-type="simple">
                  <list-item>
                    <p><bold>7.1.1. Indications</bold> 23</p>
                  </list-item>
                </list>
              </list-item>
              <list-item>
                <p><bold>7.2. Protocol for Adenosine Stress Echocardiography</bold> 23</p>
              </list-item>
              <list-item>
                <p><bold>7.3. Protocol for Regadenoson Stress Echocardiography</bold> 23</p>
              </list-item>
              <list-item>
                <p><bold>7.4. Contraindications</bold> 24</p>
              </list-item>
              <list-item>
                <p><bold>7.5. Adverse Effects</bold> 24</p>
              </list-item>
              <list-item>
                <p><bold>7.6. Diagnostic Accuracy</bold> 24</p>
              </list-item>
            </list>
          </list-item>
          <list-item>
            <p><bold>8. Other Stress Echocardiography Modalities: Pacing, Ergonovine, Handgrip, and Hyperventilation</bold> 24</p>
            <list list-type="simple">
              <list-item>
                <p><bold>8.1. Pacing Stress Echocardiography</bold> 24</p>
              </list-item>
              <list-item>
                <p><bold>8.2. Addition of Handgrip Exercise to Stress Echocardiography</bold> 24</p>
              </list-item>
              <list-item>
                <p><bold>8.3. Ergonovine and Hyperventilation Stress Echocardiography</bold> 24</p>
              </list-item>
            </list>
          </list-item>
          <list-item>
            <p><bold>9. Diastolic Stress Echocardiography</bold> 25</p>
            <list list-type="simple">
              <list-item>
                <p><bold>9.1. Normal and Abnormal Response to Exercise of Diastolic Function</bold> 25</p>
              </list-item>
              <list-item>
                <p><bold>9.2. Indications for Stress Echocardiography</bold> 25</p>
              </list-item>
              <list-item>
                <p><bold>9.3. Protocols Used in Diastolic Stress Echocardiography</bold> 26</p>
              </list-item>
              <list-item>
                <p><bold>9.4. Interpretation of Diastolic Stress Echocardiography</bold> 26</p>
              </list-item>
            </list>
          </list-item>
          <list-item>
            <p><bold>10. Stress Echocardiography in MINOCA (Myocardial Infarction with Nonobstructive Coronary Arteries) and in Microvascular Disease</bold> 27</p>
            <list list-type="simple">
              <list-item>
                <p><bold>10.1. Pathophysiology</bold> 27</p>
              </list-item>
              <list-item>
                <p><bold>10.2. Main Diagnostic Methods in MINOCA</bold> 27</p>
              </list-item>
              <list-item>
                <p><bold>10.3. The Stress Echocardiogram in MINOCA</bold> 27</p>
              </list-item>
            </list>
          </list-item>
          <list-item>
            <p><bold>11. Stress Echocardiography in Mitral Valve Disease</bold> 29</p>
            <list list-type="simple">
              <list-item>
                <p><bold>11.1. Mitral Stenosis</bold> 29</p>
              </list-item>
              <list-item>
                <p><bold>11.2. Mitral Regurgitation</bold> 30</p>
              </list-item>
              <list-item>
                <p><bold>11.3. Stress Echocardiography Protocol for Evaluation of Mitral Valve Lesions</bold> 31</p>
              </list-item>
            </list>
          </list-item>
          <list-item>
            <p><bold>12. Stress Echocardiography in Aortic Valve Disease</bold> 31</p>
            <list list-type="simple">
              <list-item>
                <p><bold>12.1. Aortic Stenosis</bold> 31</p>
              </list-item>
              <list-item>
                <p><bold>12.2. Aortic Insufficiency</bold> 32</p>
              </list-item>
            </list>
          </list-item>
          <list-item>
            <p><bold>13. Stress Echocardiography in Dilated Cardiomyopathy</bold> 33</p>
          </list-item>
          <list-item>
            <p><bold>14. Stress Echocardiography in Chagas Cardiomyopathy</bold> 34</p>
          </list-item>
          <list-item>
            <p><bold>15. Stress Echocardiography in Hypertrophic Cardiomyopathy</bold> 36</p>
          </list-item>
          <list-item>
            <p><bold>16. Stress Echocardiography in the Evaluation of Right Ventricular Function and Pulmonary Hypertension</bold> 36</p>
          </list-item>
          <list-item>
            <p><bold>17. Stress Echocardiography in Post-COVID-19 assessment</bold> 37</p>
          </list-item>
          <list-item>
            <p><bold>18. Stress Echocardiography and Coronary Flow Reserve in Native Vessels</bold> 37</p>
          </list-item>
          <list-item>
            <p><bold>19. Stress Echocardiography and Coronary Flow Reserve in Grafts</bold> 39</p>
            <list list-type="simple">
              <list-item>
                <p><bold>19.1. Stress echocardiography after myocardial revascularization</bold> 39</p>
              </list-item>
              <list-item>
                <p><bold>19.2. Coronary flow reserve after myocardial revascularization</bold> 39</p>
              </list-item>
            </list>
          </list-item>
          <list-item>
            <p><bold>20. Stress Echocardiography in the Assessment of Myocardial Viability</bold> 39</p>
            <list list-type="simple">
              <list-item>
                <p><bold>20.1. Stress Echo Protocols for Assessment of Myocardial Viability</bold> 41</p>
              </list-item>
              <list-item>
                <p><bold>20.2. Assessment of Myocardial Viability by Longitudinal Strain</bold> 41</p>
              </list-item>
            </list>
          </list-item>
          <list-item>
            <p><bold>21. Stress Echocardiography with Ultrasound Enhancing Agents for Delineation of the Endocardial Border</bold> 43</p>
            <list list-type="simple">
              <list-item>
                <p><bold>21.1. Ultrasound Enhancing Agents</bold> 43</p>
                <list list-type="simple">
                  <list-item>
                    <p><bold>21.1.1. Administration</bold> 43</p>
                  </list-item>
                </list>
              </list-item>
            </list>
          </list-item>
          <list-item>
            <p><bold>22. Stress Echocardiography with Ultrasound Enhancing Agents for Myocardial Perfusion Analysis</bold> 44</p>
          </list-item>
          <list-item>
            <p><bold>23. Stress Echocardiography with Myocardial Strain Imaging in Ischemic Heart Disease</bold> 46</p>
            <list list-type="simple">
              <list-item>
                <p><bold>23.1. Speckle Tracking-Derived Strain Versus Tissue Doppler-Derived Strain During Stress Echocardiography</bold> 46</p>
              </list-item>
              <list-item>
                <p><bold>23.2. Two-Dimensional Strain During Stress Echocardiography: Diagnostic and Prognostic Value in Coronary Artery Disease</bold> 47</p>
              </list-item>
              <list-item>
                <p><bold>23.3. Which Strain is Most Useful in Stress Echocardiography? Global or Regional? Longitudinal or Circumferential? And What is the Importance of Post-Systolic Thickening?</bold> 48</p>
              </list-item>
              <list-item>
                <p><bold>23.4. Does Strain Have Ischemic Memory?</bold> 49</p>
              </list-item>
              <list-item>
                <p><bold>23.5. Can Baseline Global Longitudinal Strain Predict Coronary Artery Disease in the Absence of Visually Apparent Wall Motion Abnormalities During Stress?</bold> 50</p>
              </list-item>
              <list-item>
                <p><bold>23.6. Limitations</bold> 51</p>
              </list-item>
            </list>
          </list-item>
          <list-item>
            <p><bold>24. Stress Echocardiography with Myocardial Strain Imaging Beyond Ischemic Heart Disease</bold> 51</p>
          </list-item>
          <list-item>
            <p><bold>25. Three-Dimensional Stress Echocardiography</bold> 52</p>
            <list list-type="simple">
              <list-item>
                <p><bold>25.1. Three-Dimensional Technology and Its Applications in Echocardiography</bold> 52</p>
              </list-item>
              <list-item>
                <p><bold>25.2. The Application of Three-Dimensional Echocardiography in Stress Echocardiography</bold> 52</p>
              </list-item>
            </list>
          </list-item>
          <list-item>
            <p><bold>26. Stress Echocardiography in the Emergency Department: Indications and Applications</bold> 54</p>
            <list list-type="simple">
              <list-item>
                <p><bold>26.1. Utility of Stress Echocardiography in the Emergency Department</bold> 55</p>
              </list-item>
            </list>
          </list-item>
          <list-item>
            <p><bold>27. Stress Echocardiography in the Heart Transplant Recipient</bold> 56</p>
          </list-item>
          <list-item>
            <p><bold>28. Stress Echocardiography in Special Subgroups (Left Bundle Branch Block, Right Bundle Branch Block, and Atrial Fibrillation)</bold> 57</p>
            <list list-type="simple">
              <list-item>
                <p><bold>28.1. Left Bundle Branch Block</bold> 57</p>
              </list-item>
              <list-item>
                <p><bold>28.2. Right Bundle Branch Block</bold> 57</p>
              </list-item>
              <list-item>
                <p><bold>28.3. Atrial Fibrillation</bold> 57</p>
              </list-item>
            </list>
          </list-item>
          <list-item>
            <p><bold>29. Stress Echocardiography for Preoperative Assessment Before Vascular Surgery, in Women, and in Older Adults</bold> 58</p>
            <list list-type="simple">
              <list-item>
                <p><bold>29.1. Preoperative Assessment Before Vascular Surgery</bold> 58</p>
              </list-item>
              <list-item>
                <p><bold>29.2. Women</bold> 58</p>
              </list-item>
              <list-item>
                <p><bold>29.3. Older Adults</bold> 59</p>
              </list-item>
            </list>
          </list-item>
          <list-item>
            <p><bold>30. Stress Echocardiography in Pediatrics: Indications and Protocols</bold> 59</p>
          </list-item>
          <list-item>
            <p><bold>31. Advantages and Disadvantages of Stress Echocardiography in Pediatrics</bold> 61</p>
          </list-item>
          <list-item>
            <p><bold>32. Prognostic Value of Stress Echocardiography</bold> 62</p>
          </list-item>
          <list-item>
            <p><bold>33. Novel Applications of Stress Echocardiography: After Radiation Therapy to the Chest and in Vasospasm</bold> 63</p>
          </list-item>
          <list-item>
            <p><bold>34. Stress Echocardiography with the ABCDE Protocol</bold> 63</p>
            <list list-type="simple">
              <list-item>
                <p><bold>34.1. The ABCDE Protocol</bold> 64</p>
              </list-item>
            </list>
          </list-item>
          <list-item>
            <p><bold>35. Recommendations for the Management of Stress Echocardiography</bold> 66</p>
          </list-item>
          <list-item>
            <p><bold>References</bold> 67</p>
          </list-item>
        </list>
        <fig id="f38">
          <graphic xlink:href=""/>
          <p>* May be considered in specific situations.</p>
        </fig>
      </sec>
      <sec>
        <title>1. The Role of Resting Echocardiography Performed at the Time of Physical or Pharmacological Stress Echocardiography</title>
        <p>One of the first descriptions of physical stress echocardiography (SE), published in 1979, compared images obtained at rest to those obtained during bicycle exercise.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Analysis of the images in the article clearly shows the technical limitations of the time, with definition issues making both resting and exercise images difficult to interpret. Even so, regional wall motion abnormalities (RWMAs) were found in 10 patients, all of whom had significant coronary artery stenoses. The method has since evolved, and resting echocardiography now includes a wide range of refined diagnostic tools, such as Doppler (in its various modalities), digital recording of cardiac cycles with a high frame rate, reliable measurements of chamber volumes, analysis of ventricular and atrial deformation, estimation of intracavitary pressures, and analysis of valve areas, as well as a vast number of cardiovascular risk markers that can be analyzed at rest. This broad range of complex analyses, allowing thorough morphological and functional evaluation, has established resting echocardiography as a standalone modality.</p>
        <p>Picano et al., in a recent European consensus statement,<sup><xref ref-type="bibr" rid="B2">2</xref></sup> set out the limited roles of resting echocardiography, performed in conjunction with stress echocardiography, including assessment of image quality, mapping windows for standard views, ruling out other obvious causes of symptoms (e.g., pericardial effusion, aortic stenosis, hypertrophic cardiomyopathy), and, above all, eliminating contraindications to stress testing, such as acute ischemia, aortic dissection, and pulmonary embolism, among others. As defined in this consensus and other guidelines,<sup><xref ref-type="bibr" rid="B3">3</xref></sup> the resting echocardiogram performed immediately before a stress echocardiogram is thus incomplete, as its purpose is to observe parameters that may undergo dynamic changes. It is a "snapshot" focused on the clinical indication for the imaging modality and on the resting abnormalities that should be evaluated under stress, and therefore cannot be regarded or requested as a complete morphological and functional assessment of a standard echocardiogram.</p>
        <p>Therefore, the conventional resting echocardiogram is a distinct examination from SE and should preferably be performed at another time. It is also the first-line modality of choice which should precede SE to rule out situations that would limit, contraindicate, or altogether prevent performance of SE, such as those mentioned above, as well as assess individual patient variations which may limit ultrasound image quality and thus compromise interpretation of SE.</p>
      </sec>
      <sec>
        <title>2. The Evolution of Stress Echocardiography: from Inception to the Present Day</title>
        <p>Coronary artery disease remains a major cause of morbidity and mortality. Therefore, diagnostic and therapeutic resources capable of mitigating its effects from both an individual and community perspective remain objects of great medical interest, with a significant potential for socioeconomic impact.</p>
        <p>The development of accessible diagnostic methods that are easy to perform, reproducible, low-cost, preferably non-invasive, and have good accuracy has always been a focus of research in cardiology, especially in the field of coronary artery disease.</p>
        <p>The use of drugs to induce an imbalance between myocardial oxygen supply and consumption was initially proposed as an adjunct to electrocardiography, first using dipyridamole, and later, dobutamine. The induction of pharmacological stress in conjunction with echocardiography only became established following the initial work of Picano et al., using dipyridamole, and Berthe &amp; Pi&#233;rard in 1986, using dobutamine.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> These have become the most established drugs in daily clinical practice ever since, with well-defined dosage protocols, diagnostic criteria, and safety levels, often further combined with atropine to maximize the heart rate levels achieved and thus optimize diagnostic yield.<sup><xref ref-type="bibr" rid="B6">6</xref>-<xref ref-type="bibr" rid="B13">13</xref></sup></p>
        <p>Physical exercise, whether performed on a treadmill or cycle ergometer, remains the first-choice stress modality for patients who are physically and clinically able to tolerate exertion, as it is a more physiological method. In patients with limitations to physical exertion, such as those with orthopedic or neurological conditions, lung diseases, visual impairments, or poor coordination during physical activity, among others, pharmacological protocols are the preferred alternative.<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
        <p>Both exercise and pharmacological SE have proven, through results obtained in recent decades, to be safe in older adults, women, patients with coronary artery disease, chronic kidney disease, valvular heart disease, and peripheral vascular disease, as well as in the post-transplant setting. Their diagnostic performance indices are quite high, similar to those of nuclear medicine methods, and they exhibit high agreement with anatomical-structural methods, such as computed tomography (CT) angiography and coronary angiography.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B14">14</xref>,<xref ref-type="bibr" rid="B16">16</xref></sup></p>
        <p>It is worth noting that, in addition to its purpose of detecting myocardial ischemia, SE is extremely valuable for assessing myocardial viability in patients who have already experienced a cardiac event &#8211; a pathophysiological concept with diagnostic, therapeutic, and prognostic relevance for those with coronary artery disease.<sup><xref ref-type="bibr" rid="B10">10</xref>-<xref ref-type="bibr" rid="B12">12</xref></sup></p>
        <p>Finally, it also bears stressing that, beyond its role in coronary artery disease, SE is widely indicated in the assessment of diastolic dysfunction, especially in patients with heart failure with preserved ejection fraction (HFpEF); non-ischemic (infiltrative or storage) cardiomyopathies; mitral and aortic valve disease; congenital heart disease; pulmonary hypertension; athlete's heart; graft vascular disease; and in the post-transplant setting, among other indications.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B14">14</xref>-<xref ref-type="bibr" rid="B20">20</xref></sup></p>
      </sec>
      <sec sec-type="methods">
        <title>3. Ischemia-Inducing Methods</title>
        <p>The primary objective of SE in coronary artery disease is to demonstrate the development of myocardial ischemia, its extent, and its distribution, and, secondarily, to stratify risk by demonstrating hemodynamic changes &#8211; ventricular dilatation, decreased blood pressure, diastolic dysfunction, altered coronary flow reserve (CFR) and/or myocardial reserve (MR), among others.<sup><xref ref-type="bibr" rid="B21">21</xref></sup></p>
        <p>Myocardial ischemia may manifest as the presence of significant obstructive epicardial lesions (&gt; 50% left main coronary artery [LMCA] or &gt; 70% other epicardial arteries), or as the presence of a compromised microcirculation without significant epicardial lesions. The utility of each test is based on their ability to detect these abnormalities<sup><xref ref-type="bibr" rid="B22">22</xref></sup> (<xref ref-type="fig" rid="f39">Figure 3.1</xref>).</p>
        <fig id="f39">
          <label>Figure 3.1</label>
          <caption>
            <title>Anatomical and functional objectives of stress echocardiography. LMCA: left main coronary artery; EA: epicardial artery; CFR: coronary flow reserve; MR: myocardial reserve; LBBB: left bundle branch block.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>Another interesting role of SE is to objectively demonstrate a decrease in coronary flow through non-significant intermediate coronary lesions, with no evidence of ischemia on conventional tests, through measurement of the CFR.<sup><xref ref-type="bibr" rid="B23">23</xref></sup></p>
        <sec>
          <title>3.1. Exercise Stress Echocardiograph (Bicycle, Treadmill, or Recumbent Bicycle/Echo Couch)</title>
          <p>Exercise SE is the most physiological of all provocative tests. It is based on demonstrating ischemia through an increase in the double product (maximum systolic blood pressure &#215; peak heart rate achieved) and myocardial oxygen consumption. It is considered the first-line modality of choice, except when contraindicated or unavailable. Its utility is greatest in patients with significant epicardial lesions, primarily affecting the subendocardial layer, as assessed by wall motion (thickening), extent, and distribution, with significant risk when involvement includes three or more segments. Furthermore, it allows for simultaneous observation of the hemodynamic repercussions of ischemia: diastolic dysfunction (transmitral flow, E/e&#8242;), ventricular dilatation, mitral regurgitation, reduced myocardial reserve, arrhythmias, and pulmonary B lines, among others.</p>
        </sec>
        <sec>
          <title>3.2. Pharmacological Stress Echocardiography</title>
          <list list-type="alpha-lower">
            <list-item>
              <p>Dobutamine: based on ability to demonstrate ischemia in the presence of significant epicardial lesions through an increase in double product and myocardial oxygen consumption by acting on adrenergic receptors, increasing cardiac inotropism and chronotropism. Used in patients who are unable to exercise, at centers where exercise SE is unavailable, or to assess myocardial ischemia and viability (the latter under discussion) in patients with baseline regional wall motion abnormalities. As useful as exercise SE;</p>
            </list-item>
            <list-item>
              <p>Vasodilators (dipyridamole and adenosine): act on the microcirculation, demonstrating ischemia through direct vasodilation of healthy arterioles to the detriment of diseased arterioles, inducing the so-called "coronary steal" phenomenon. This occurs due to a buildup of adenosine in the vascular system (indirectly when dipyridamole is given and directly when exogenous adenosine is given), where it exerts a very potent vasodilating effect. These drugs do not significantly increase the double product, allowing for a more practical assessment of CFR and myocardial strain. They are useful in patients with complete left bundle branch block (LBBB), a permanent pacemaker, contraindications to exercise or dobutamine, suspected microvascular disease, atrial fibrillation, hypertension, and those with symptomatic epicardial lesions.</p>
            </list-item>
          </list>
        </sec>
        <sec>
          <title>3.3. Stress Echocardiography in Coronary Spasm Provocative Testing</title>
          <list list-type="alpha-lower">
            <list-item>
              <p>Ergonovine test: the "gold standard" due to its high sensitivity (93%) and specificity (91%). Stimulates &#945;-adrenergic receptors.<sup><xref ref-type="bibr" rid="B24">24</xref>-<xref ref-type="bibr" rid="B26">26</xref></sup></p>
            </list-item>
            <list-item>
              <p>5-Hydroxytryptamine (serotonin): is high-risk, not indicated for routine use, has not achieved clinical reproducibility. Contractile changes indicative of ischemia occur early, even before pain or electrocardiogram (ECG) changes; may induce Takotsubo syndrome.<sup><xref ref-type="bibr" rid="B27">27</xref></sup></p>
            </list-item>
            <list-item>
              <p>Hyperventilation test: induces coronary spasm by decreasing H+ ions in the plasma with an increase in pH (alkalosis), thus increasing intracellular calcium, inducing contraction and vasospasticity of arterial smooth muscle cells in the epicardial coronary arteries. Highly sensitive (90%).<sup><xref ref-type="bibr" rid="B28">28</xref>,<xref ref-type="bibr" rid="B29">29</xref></sup></p>
            </list-item>
            <list-item>
              <p>Cold test: In the presence of endothelial dysfunction and elevated catecholamines, coronary vasoconstriction occurs.<sup><xref ref-type="bibr" rid="B28">28</xref>,<xref ref-type="bibr" rid="B29">29</xref></sup></p>
            </list-item>
            <list-item>
              <p>The combination of exercise or dobutamine SE with the cold test and/or hyperventilation test can increase sensitivity and diagnostic power to identify coronary vasospasm.</p>
            </list-item>
          </list>
        </sec>
        <sec>
          <title>3.4. Pacing Stress Echocardiography</title>
          <p>Performed in patients with an implanted permanent pacemaker (PPM) with right atrial and/or right ventricular stimulation. The mechanism involves using the pacemaker to increase the heart rate, which increases the double product and induces ischemia. Regional wall thickening is assessed by taking into account the septal movements caused by the pacemaker catheter implantation site (<xref ref-type="fig" rid="f40">Figure 3.2</xref>).</p>
          <fig id="f40">
            <label>Figure 3.2</label>
            <caption>
              <title>Pacemaker stress echocardiography according to the site of stimulation and septal movement.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <p>This modality is highly sensitive (98%) and safe (96%), as the heart rate can be reduced instantaneously.<sup><xref ref-type="bibr" rid="B30">30</xref>,<xref ref-type="bibr" rid="B31">31</xref></sup></p>
          <p>It is a good alternative for diagnosis of ischemia in patients who cannot exercise, have contraindications to pharmacological testing, and have had a PPM implanted (<xref ref-type="fig" rid="f40">Figure 3.2</xref>).</p>
        </sec>
      </sec>
      <sec>
        <title>4. Exercise Stress Echocardiography (Treadmill, Cycle Ergometer or Bicycle)</title>
        <p>Exercise stress echocardiography (ESE) is a testing modality that investigates myocardial function in an effective, physiological, and safe manner, seeking to replicate the daily routine of patients with preserved physical capacity. This practical, non-invasive examination provides valuable information regarding the diagnosis of myocardial ischemia, the behavior of blood pressure, and the etiology of cardiac arrhythmias, while also allowing evaluation of the behavior of pressure gradients in the left ventricular outflow tract, pulmonary artery systolic pressure, and valvular lesions. It is worth noting that analysis of these parameters must be correlated with the onset of symptoms (if any) before, during, and after physical exertion.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Over the last two decades, the utility of this methodology for managing patients with various conditions, such as coronary artery disease, cardiomyopathies, valvular heart disease, and cardiac arrhythmias, has been demonstrated and recognized, including its utility in preoperative risk stratification for noncardiac surgery.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
        <p>Considering the development of new cardiac imaging modalities, such as CT coronary angiography and cardiac magnetic resonance (CMR) imaging, ESE has made surprising progress. Although CMR has demonstrated indisputable ability to diagnose various cardiac conditions in detail, its accuracy for diagnosing myocardial ischemia is not superior to that of ESE or myocardial perfusion scanning. Furthermore, because ESE is an easily accessible, low-cost, highly reproducible methodology, it is very useful for monitoring patients with these heart conditions over time.<sup><xref ref-type="bibr" rid="B33">33</xref></sup> It is important that new generations of echocardiographers also take an interest in the method as a useful modality for both clinical diagnostics and scientific research, always seeking to improve their ability to obtain images of satisfactory quality, so as not to jeopardize interpretation.<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
        <p>It is the echocardiographer's duty to conduct initial assessment of the clinical condition of the patient to be studied, as well as ascertain their preference of treadmill, cycle ergometer, or reclining ergometer ("echo couch") when the echocardiography laboratory offers more than one choice. It is also important to discuss the limitations of the various stress-inducing methods, so that the choice of method is based on the physical capacity of the individual as well as on the local conditions of each laboratory. The patient should be made aware that ESE integrates four components: ECG, the exercise stress test per se, a targeted transthoracic echocardiogram, and the stress echocardiogram, each of which must also take into account the patient's symptoms and physical capacity. The echocardiographer, in turn, must supervise every step of the examination: the resting phase, the pre-test phase, the stress phase, and finally, the recovery phase. The presence of paramedics throughout the examination is also necessary to ensure, above all, that the recording of ECG tracings and echocardiographic images is not compromised.</p>
        <p>In most facilities, as is the case in our echo lab, the treadmill is the cornerstone of ESE, primarily because it is the preferred exercise modality for the majority of patients. Using this machine, an experienced echocardiographer can, in most cases, get the patient to attain the recommended maximum heart rate (220 &#8211; age), especially if the patient is aware of the need to reach this target. However, the quality of echocardiographic images is often compromised when maximum exertion is reached, due to lung hyperventilation. Therefore, it is recommended that the patient be made to reach an intermediate heart rate between the submaximal rate (85% of the maximum heart rate) and the maximum heart rate for optimal image interpretation, as well as for images to ideally be obtained no later than 90 seconds after maximum exertion (when using a treadmill). This procedure facilitates the acquisition and recording of echocardiographic images at peak physical exertion, with the patient lying on the examination table in the left lateral decubitus position, which should be obtained rapidly after achieving the target heart rate in order not to reduce the sensitivity of the test.. When using a cycle ergometer or stationary bicycle, the endpoint of exertion is almost always determined by the patient (provided they reach the target heart rate to ensure that the test is conclusive), and obtaining images during exertion while the patient is seated is more laborious for the echocardiographer. The reclining ergometer or "echo couch" was developed to address this issue. It makes capturing images somewhat easier, since the individual remains in a semi-supine position throughout the examination.<sup><xref ref-type="bibr" rid="B32">32</xref></sup> The most elevated setting on the reclining ergometer allows for the best test quality, by allowing the patient to exert greater thrust with the legs.</p>
        <p>Currently, in addition to the classic indications for ESE &#8211; patients who are capable of physical exertion and present with chest pain, suspected or known coronary artery disease, fatigue, or suspected HFpEF &#8211; the 2021 American Heart Association Guidelines for Hypertrophic Cardiomyopathy (HCM)<sup><xref ref-type="bibr" rid="B33">33</xref></sup> recommend initial assessment with left ventricular outflow tract (LVOT) gradient measurement in all HCM patients at rest, during Valsalva strain, and in semi-supine, sitting, or standing positions. For asymptomatic patients with a resting LVOT gradient &lt; 50 mm Hg, ESE is indicated. HCM is considered obstructive when the gradient is &gt; 50 mm Hg. A labile or obstructive LVOT gradient is defined as one not observed during resting echocardiography, but provoked by stress testing. It is also worth noting that a resting LVOT gradient &#8805; 50 mm Hg is a contraindication to exercise testing. The presence of systolic anterior motion (SAM) of the mitral valve, mitral regurgitation, ventricular dyssynergy, and left ventricular diastolic dysfunction grade 3, should also be assessed<sup><xref ref-type="bibr" rid="B34">34</xref></sup> (<xref ref-type="fig" rid="f41">Figure 4.1</xref>).</p>
        <fig id="f41">
          <label>Figure 4.1</label>
          <caption>
            <title>Proposed flow chart for the use of exercise stress echocardiography in patients with HCM without a gradient (LVOTG = 0 mm Hg) or with a gradient (LVOTG &lt; 50 mm Hg). HCM: hypertrophic cardiomyopathy; LVOTG: left ventricular outflow tract gradient.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>ESE protocols for the stationary bicycle/cycle ergometer, treadmill, and reclining ergometer/echo couch modalities are given in <xref ref-type="fig" rid="f42">Figure 4.2</xref>.</p>
        <fig id="f42">
          <label>Figure 4.2</label>
          <caption>
            <title>Protocols for exercise stress echocardiography using a stationary bicycle/cycle ergometer, treadmill, or reclining ergometer/echo couch (in the supine position). Image capture on cycle and reclining ergometers is continuous, while on a treadmill images are only captured before and immediately after exertion. The Bruce protocol remains widely used for treadmill tests to this day, whereas on cycle or reclining ergometers, the Balke protocol is preferred, with load increased gradually (in 25W increments), as shown in the figure every 2 minutes,<sup><xref ref-type="bibr" rid="B2">2</xref></sup> and may go beyond 125 W.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
      </sec>
      <sec>
        <title>5. Dobutamine Stress Echocardiography in the Assessment of Myocardial Ischemia</title>
        <p>In myocardial ischemia, the basis of pharmacological stress echocardiography with dobutamine (DSE) is the evaluation of the physiological response of the myocardium to different degrees of coronary artery obstruction, especially in terms of subendocardial perfusion, while the subepicardial layer is only affected at a later stage if ischemia persists.<sup><xref ref-type="bibr" rid="B35">35</xref>,<xref ref-type="bibr" rid="B36">36</xref></sup></p>
        <p>Indication. DSE is an alternative method for evaluating myocardial ischemia when a patient is unable to perform physical exercise. DSE was initially developed for assessment of patients with known or suspected coronary artery disease.<sup><xref ref-type="bibr" rid="B37">37</xref></sup> Its most common indication is to assess the presence, location, or extent of myocardial ischemia. Its high specificity (88%) yields a high negative predictive value for myocardial infarction and cardiac death.<sup><xref ref-type="bibr" rid="B38">38</xref></sup> Indications for DSE as per the latest guidelines are listed in <xref ref-type="table" rid="t34">Table 5.1</xref>.<sup><xref ref-type="bibr" rid="B39">39</xref></sup></p>
        <table-wrap id="t34">
          <label>Table 5.1</label>
          <caption>
            <title>Indications for dobutamine stress echocardiography in myocardial ischemia<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B12">12</xref>,<xref ref-type="bibr" rid="B35">35</xref>-<xref ref-type="bibr" rid="B43">43</xref></sup></title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="100%">
              <col/>
            </colgroup>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle">1) Diagnosis of CAD with intermediate pretest probability.</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">2) Acute chest pain in intermediate-risk patients (no abnormalities on ECG and negative biomarkers).</td>
              </tr>
              <tr>
                <td align="left" valign="middle">3) Symptomatic angina in patients with a history of stent or CABG.</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">4) Moderate coronary obstruction detected by CT angiography or coronary angiography: functional significance.</td>
              </tr>
              <tr>
                <td align="left" valign="middle">5) Risk stratification after myocardial infarction.</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">6) Etiologic diagnosis of dyspnea.</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <p>DSE may not detect ischemia of small distal vessels, and patients with obesity or emphysema may have poor acoustic windows, resulting in suboptimal images even with the use of ultrasound enhancement or ultrasound contrast agents.</p>
        <p>The selection of the most appropriate examination is based on the patient's clinical picture, including the nature of the patient's symptoms, their risk profile, and the strengths and limitations of the chosen test modality.<sup><xref ref-type="bibr" rid="B40">40</xref></sup></p>
        <p>Equipment. Some equipment and drugs must be present in the echo lab for DSE (<xref ref-type="table" rid="t35">Table 5.2</xref>).<sup><xref ref-type="bibr" rid="B39">39</xref></sup></p>
        <table-wrap id="t35">
          <label>Table 5.2</label>
          <caption>
            <title>Equipment and medications required for performing pharmacological stress echocardiography with dobutamine <sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B12">12</xref>,<xref ref-type="bibr" rid="B35">35</xref>-<xref ref-type="bibr" rid="B43">43</xref></sup></title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="100%">
              <col/>
            </colgroup>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle">
                  <italic>1) Digital echocardiography system with stress protocol and ability to display images simultaneously in quad-screen format.</italic>
                </td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">2) Device for electrocardiographic and blood pressure monitoring (preferably continuous).</td>
              </tr>
              <tr>
                <td align="left" valign="middle">3) Crash cart (including drugs and supplies for cardiopulmonary resuscitation and a defibrillator/cardioverter).</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">4) Oxygen supply (if necessary).</td>
              </tr>
              <tr>
                <td align="left" valign="middle">5) Equipment for intubation.</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">6) Dobutamine infusion pump.</td>
              </tr>
              <tr>
                <td align="left" valign="middle">7) Drugs for the management of allergic reactions, in addition to dobutamine, atropine, and metoprolol (and other drugs and their antidotes, if a different pharmacological protocol is used).</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <sec>
          <title>5.1. Dobutamine Stress Echocardiography Protocol</title>
          <p>Defined in 2007 by the American Society of Echocardiography guidelines.<sup><xref ref-type="bibr" rid="B12">12</xref></sup></p>
          <p>Patient preparation: Patients should fast for 4 to 6 hours before the test and may continue to take their usual medications. However, the following should be discontinued at least 24 hours before the test: amiodarone, calcium channel blockers, nitrates, substances containing caffeine and nicotine (for dipyridamole stress echocardiography in particular), and, most importantly, beta blockers (to avoid a false-negative result).<sup><xref ref-type="bibr" rid="B37">37</xref></sup> The latter should be discontinued ideally 3 to 4 days before the examination, if the goal is to diagnose myocardial ischemia.</p>
          <p>Stages of the procedure: 1) Placement of IV access; 2) Placement of 12-lead electrodes; 3) Placement of sphygmomanometer; 4) Focused resting echocardiogram, for later comparison with images obtained under stress; 5) Image acquisition at rest, low-dose, intermediate-dose (optional), peak of dobutamine effect and recovery phase, with cine loops to be archived of the main views: long axis, short axis (at the level of the papillary muscles), apical 4-chamber, apical 2-chamber and, optionally, apical 3-chamber (adds value for evaluation of the LV apex or as a replacement for the parasternal long-axis view). Some authors choose to acquire all images through the apical window (apical 4-, 3-, and 2-chamber views). The key aspect is to observe all walls of the left ventricle irrigated by the main coronary vessels; 6) Continuous ECG, heart rate (HR), and blood pressure (BP) monitoring; 7) If necessary, isometric exercise (handgrip) will be performed in conjunction; atropine infusion if necessary, to enhance the examination; metoprolol infusion if necessary, to antagonize the effects of dobutamine (when necessary); 8) Report of examination.</p>
          <p>Dobutamine Action and Pharmacokinetics: Dobutamine exhibits a strong adrenergic agonist effect, acting on beta1 receptors to increase heart rate and contractility and on beta2 receptors to cause peripheral vasodilation. Its action begins 1 to 2 minutes after infusion, and it has a half-life of 2 minutes. Dobutamine is the most commonly used agent for pharmacological SE due to its high sensitivity and controllable side effect profile.<sup><xref ref-type="bibr" rid="B37">37</xref></sup> It is metabolized in the liver and peripheral tissues, but there is no need for dose reduction in patients with renal or hepatic impairment. It is usually administered in escalating doses, starting at 5 mcg/kg/min and increasing at 3-minute intervals up to 10, 20, 30, and 40 mcg/kg/min. Dobutamine may be started at a low dose of 2.5 mcg/kg/min and titrated to a dose of 7.5 mcg/kg/min to facilitate the recognition of myocardial viability in segments that are already abnormal (akinetic) at rest.</p>
          <p>A conclusive test requires reaching the target heart rate (85% of the maximum heart rate predicted for age). However, the development of new contractility abnormalities or worsening of preexisting abnormalities should prompt termination of the test due to ischemia. Additionally, significant arrhythmias, severe arterial hypertension, and intolerable symptoms may also lead to test interruption. When the target heart rate cannot be achieved with dobutamine alone, maximal isometric exercise and/or atropine may be added to increase the sensitivity of the test, particularly in patients who are on beta blockers, calcium channel blockers, or nitrates, as well as in those with single-vessel disease.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B41">41</xref>,<xref ref-type="bibr" rid="B42">42</xref></sup> Care should be taken when classifying a test as "submaximal" when the patient reaches 85% of the predicted maximum heart rate for age. This level corresponds to the target heart rate (i.e., the submaximal heart rate, 85% of maximum) and is therefore sufficient to characterize the test as conclusive, rather than submaximal or inconclusive.</p>
          <p>Atropine: administered in doses of 0.25 to 0.5 mg at intervals of 30 seconds to 1 minute as needed to achieve the target heart rate, up to a total dose of 2 mg. The 0.25 mg dose is suggested for older adults, patients with a small body surface area, patients with neurological disorders or those who are already near the target HR, to avoid untoward effects. Administering atropine at the lowest dose of dobutamine (20 or 30 mcg/kg/min) facilitates earlier achievement, with fewer side effects, a lower cumulative dose of dobutamine, and a shorter test duration. Discontinuation of beta-blockers facilitates reaching the target HR, and inadequate discontinuation may lead to episodes of hypertension or arrhythmia <sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B41">41</xref></sup> at peak dobutamine effect, due to sudden loss of beta-adrenoceptor blockade.</p>
          <p>Beta blockers: can be administered to reverse the effects of dobutamine (their main purpose in this setting), but can also be used to increase the sensitivity of the test for patients with single-vessel disease when administered at peak dobutamine stress.<sup><xref ref-type="bibr" rid="B42">42</xref></sup></p>
          <p>Patients may develop minor or more significant arrhythmias, such as atrial fibrillation and/or non-sustained ventricular tachycardia, which usually resolve after discontinuation of the dobutamine infusion; in such cases, beta blockers should be administered. If sustained ventricular tachycardia occurs, one should first consider myocardial ischemia.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
          <p>Drugs used in DSE, their doses and side effects are listed in <xref ref-type="table" rid="t36">Table 5.3</xref>.</p>
          <table-wrap id="t36">
            <label>Table 5.3</label>
            <caption>
              <title>Intravenous drugs used during stress echocardiography, their adverse effects, and contraindications<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B12">12</xref>,<xref ref-type="bibr" rid="B35">35</xref>-<xref ref-type="bibr" rid="B43">43</xref></sup></title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup width="50%">
                <col/>
                <col/>
              </colgroup>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle">Dobutamine:</td>
                  <td align="center" valign="middle">Dosage: 5 to 40 mcg/kg/min, increased gradually every 3 minutes.<break/> Adverse effects: nausea, tremor, palpitations, headache, hypotension, hypertension, chest pain, arrhythmia.<break/> Contraindications are listed in <xref ref-type="table" rid="t5">Table 5</xref>.4.</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">Atropine:</td>
                  <td align="center" valign="middle">Dose: up to 2 mg, starting at a dose of 20 or 30 mcg of dobutamine (early protocol), unless test cessation is indicated.<break/> Adverse effects: tachycardia, palpitations, dry mouth, mydriasis, nausea, agitation, urinary retention, increased intraocular pressure.<break/> Contraindications: closed-angle glaucoma, prostate hypertrophy, urinary retention.</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle">Metoprolol</td>
                  <td align="center" valign="middle">Dose: 1 to 10 mg.<break/> Adverse effects: bradycardia, hypotension, dizziness, headache. <break/>Contraindications: bronchial asthma, severe lung disease, tachy-brady syndrome, AV block.</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
          <p>Absolute and relative contraindications: the contraindications to all modalities of stress testing are summarized in <xref ref-type="table" rid="t37">Table 5.4</xref>.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
          <table-wrap id="t37">
            <label>Table 5.4</label>
            <caption>
              <title>Contraindications to dobutamine stress echocardiography in myocardial ischemia<sup><xref ref-type="bibr" rid="B38">38</xref>,<xref ref-type="bibr" rid="B39">39</xref>,<xref ref-type="bibr" rid="B43">43</xref></sup></title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup width="100%">
                <col/>
              </colgroup>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr style="background-color:#76B4CF">
                  <td align="left" valign="middle">
                    <bold>Absolute contraindications</bold>
                  </td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle">1) Acute MI in last 3-5 days</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">2) Unstable angina</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle">3) Uncontrolled, symptomatic arrhythmia with hemodynamic instability</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">4) Severe, symptomatic aortic stenosis</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle">5) Acute myocarditis or pericarditis</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">6) Severe hypertension (BP &gt; 200/110 mm Hg at rest)</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle">7) Active endocarditis</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">8) Pulmonary embolism or pulmonary infarction</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle">9) Obstructive hypertrophic cardiomyopathy</td>
                </tr>
                <tr>
                  <td style="border-bottom: thin solid; border-color: #000000" align="left" valign="middle">10) Recent or mobile ventricular thrombus</td>
                </tr>
                <tr style="background-color:#76B4CF">
                  <td align="left" valign="middle">
                    <bold>Relative contraindications</bold>
                  </td>
                </tr>
                <tr>
                  <td align="left" valign="middle">1) Hyperthyroidism, severe anemia, recent stroke</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle">2) Intracranial or thoracic aortic aneurysm (&gt;40 mm).</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">3) Moderate aortic stenosis</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
          <p>Informed consent: Must be signed by all patients before the test.</p>
          <p>Image acquisition: The echocardiographer should ensure that all images are obtained on the same plane and at the same depth throughout the examination, for more reliable comparison in quad-screen format.<sup><xref ref-type="bibr" rid="B38">38</xref></sup> Adjustments should be made while obtaining the baseline resting images and maintained throughout the examination.</p>
        </sec>
        <sec>
          <title>5.2. Type of Myocardial Response</title>
          <p>A normal DSE is defined by the presence of normal regional and global wall motion at rest, regional and global hyperkinesis at stress, and a significant reduction in LV chamber size due to reduced preload and afterload (physiological left ventricular cavity obliteration) (<xref ref-type="fig" rid="f43">Figure 5.1</xref>).</p>
          <fig id="f43">
            <label>Figure 5.1</label>
            <caption>
              <title>Dobutamine stress echocardiography, 2D echocardiography &#8211; normal left ventricular response: reduction of the left ventricular cavity and hyperkinesis of all walls.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <p>An ischemic response is defined by the development of a new or worsening wall motion abnormality during stress, affecting at least one myocardial segment (<xref ref-type="fig" rid="f44">Figure 5.2</xref>).</p>
          <fig id="f44">
            <label>Figure 5.2</label>
            <caption>
              <title>Dobutamine stress echocardiography, 2D echocardiography &#8211; Lateral ischemia and septum with dilatation of the left ventricle (LV).</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <p>Myocardial ischemia can be caused by epicardial vessel disease or by other causes, such as microvascular disease, a hypertensive response to exercise, or underlying cardiomyopathy.</p>
          <p>A severe resting wall motion abnormality, such as akinesis, which remains unchanged with stress is considered a "fixed response" and represents a transmurally infarcted region or one with a limited epicardial rim of viability. It should be noted that akinesis becoming dyskinesis is considered to represent a mechanical response of an infarcted segment or increased intraventricular pressure, not ischemia.</p>
          <p>The presence of any aneurysm should be reported, due to its prognostic and therapeutic implications.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
          <p>The differences in regional and global wall motion responses to DSE stress are listed in <xref ref-type="table" rid="t38">Table 5.5</xref>.</p>
          <table-wrap id="t38">
            <label>Table 5.5</label>
            <caption>
              <title>Types of response to dobutamine stress echocardiography as compared to rest and low-dose states</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup width="100%">
                <col/>
              </colgroup>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="middle"><bold>Normal regional response:</bold> Hyperkinesis and increased contractile force.</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle"><bold>Ischemic regional response:</bold> Hypokinesis and reduced contractile force.</td>
                </tr>
                <tr>
                  <td align="left" valign="middle"><bold>Normal global response:</bold> decrease in end-diastolic and end-systolic volume and a marked increase in ejection fraction.</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle"><bold>Ischemic global response:</bold> decrease in ejection fraction and ventricular cavity dilatation.</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
          <p>Cessation of DSE: DSE should be ceased: 1- when the target heart rate is reached; 2- if regional wall motion abnormalities are detected in at least 2 segments; 3- upon onset of test-limiting symptoms or any complex arrhythmia; 4- upon onset of any hypotension or significant hypertension (SBP &#8805; 220-240 mm Hg and/or DBP &#8805; 120 mm Hg); 5- at the end of the protocol. The use of ultrasound enhancing agents or contrast should be considered to improve endocardial definition when two or more contiguous segments are poorly visualized at rest on apical view.</p>
          <p>The adverse effects most commonly observed during DSE are a feeling of warmth, nausea, chills, urinary urgency, palpitations (secondary to tachycardia) and, rarely, mild headache.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Severe headache in response to dobutamine should prompt suspicion of hypertension.</p>
          <p>Test interpretations and conclusions in myocardial ischemia are listed in <xref ref-type="table" rid="t39">Table 5.6</xref>.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
          <table-wrap id="t39">
            <label>Table 5.6</label>
            <caption>
              <title>Interpretation of segmental myocardial thickening in the results of pharmacological stress echocardiography with dobutamine for the detection of myocardial ischemia</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup width="100%">
                <col/>
              </colgroup>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="middle">1. Rest = normal Stress = hyperkinesis Conclusion = normal</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle">2. Rest = normal or hypokinesis Stress = hypokinesis or akinesis Conclusion = ischemia</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">3. Rest = akinesis Stress = improves at low dose and worsens at high dose Conclusion = viability and ischemia</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle">4. Rest = akinesis Stress = akinesis or dyskinesis Conclusion = scarring/fibrosis</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
          <p>Test endpoints: Absolute and relative endpoints for DSE are listed in <xref ref-type="table" rid="t40">Table 5.7</xref>.</p>
          <table-wrap id="t40">
            <label>Table 5.7</label>
            <caption>
              <title>Absolute and relative endpoints for stress echocardiography</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup width="100%">
                <col/>
              </colgroup>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="middle">1- Reached 85% of the maximum heart rate (HR) predicted for age (220-age).<break/> 2- Maximum drug dose administered (end of protocol) or limiting symptoms. <break/>3- Echocardiographic evidence of myocardial ischemia (echo positivity), regardless of any other factor.<break/> 4- Sustained ventricular tachycardia/complex arrhythmias.<break/> 5- Symptomatic decline in blood pressure (SBP &gt; 20 mm Hg) or heart rate.</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle">Relative endpoints for stress echocardiography:<break/> 1- New or worsening regional wall motion abnormality in at least one previously unaffected segment or in any segments already abnormal at rest.<break/> 2- Left ventricular dilatation.<break/> 3- Onset of arrhythmias (atrial fibrillation, supraventricular tachycardia, complex ventricular arrhythmia).</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
          <p>Accuracy of the method &#8211; Several studies have demonstrated excellent accuracy of DSE, using coronary arteriography as the gold standard for comparison. For detection of coronary artery disease (CAD), DSE has sensitivity similar to that of tomographic nuclear perfusion imaging, with higher specificity. DSE has greater sensitivity for the detection of lesions in the left anterior descending artery and in LMCA or multivessel disease.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
          <p>If ischemia is not detected and stress is inadequate, either due to limited acoustic window or failure to achieve the target heart rate, the test result may be false negative.</p>
          <p>Patients with false-positive stress echocardiogram results have similar outcomes to those with true-positive results. They should receive intensive-risk factor management and careful follow-up.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
          <p>Overall interpretation &#8211; The report should include one of the following as a conclusion:</p>
          <p>Normal, ischemia, absence of wall thickening (fibrosis), or a combination of these findings (provided the appropriate endpoint is reached). If the end of the protocol was reached uneventfully but the target heart rate was not achieved, the test can be described as inconclusive (or negative up to the heart rate actually reached). In the latter case, it is important to stress that the sensitivity of the test for diagnosing myocardial ischemia is reduced in such cases because the target heart rate was not reached.</p>
          <p>For image interpretation, the size, shape, and function of the LV are compared at each stage in 4 simultaneous views and in each view in simultaneous stages. These images must be obtained from the same position at each stage of the test. In the normal response to stress, the LV is smaller compared to its resting dimension, its shape is maintained, and endocardial excursion increases, with a consequent increase in myocardial thickness.<sup><xref ref-type="bibr" rid="B43">43</xref></sup></p>
          <p>Left ventricular dilatation and reduced LV ejection fraction during DSE generally indicate extensive ischemia.</p>
          <p>Each segment is scored as follows:</p>
          <list list-type="order">
            <list-item>
              <p>Normal wall motion (myocardial thickening &gt; 50%);</p>
            </list-item>
            <list-item>
              <p>Hypokinesis (myocardial thickening 10%&#8211;50%);</p>
            </list-item>
            <list-item>
              <p>Severe hypokinesis or akinesis (myocardial thickening &lt; 10%);</p>
            </list-item>
            <list-item>
              <p>Dyskinesis (paradoxical septal motion and systolic bulging).</p>
            </list-item>
          </list>
          <p>The wall motion score index (WMSI) is calculated by dividing the sum of all segment scores by the total number of myocardial segments (16 or 17, if including the LV apex). In normal, non-ischemic myocardium, the WMSI is 1.<sup><xref ref-type="bibr" rid="B39">39</xref></sup> The echocardiographic views to be obtained and the corresponding coronary perfusion are shown in <xref ref-type="table" rid="t41">Table 5.8</xref>.</p>
          <table-wrap id="t41">
            <label>Table 5.8</label>
            <caption>
              <title>Echocardiographic assessment of the segments of the heart and coronary irrigation territories</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 style="background-color:#76B4CF">
                  <th align="left" valign="middle">VIEW</th>
                  <th align="center" valign="middle">CORONARY SUPPLY</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="middle">Parasternal long-axis or apical 3C</td>
                  <td align="center" valign="middle">LAD, RCA and CX</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle">Apical 4C</td>
                  <td align="center" valign="middle">LAD, RCA and CX</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">Apical 2C</td>
                  <td align="center" valign="middle">LAD, RCA</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle">Parasternal short-axis view</td>
                  <td align="center" valign="middle">LAD, RCA and CX</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN15">
                <p>LAD: left anterior descending artery; RCA: right coronary artery; CX: circumflex artery.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>Difficulty in interpreting test results: patients with pacemakers may have an inadequate rate response and may also exhibit regional wall motion abnormalities due to the stimulation effect; therefore, dobutamine often fails to elicit adequate responses in these patients.</p>
          <p>Risk stratification and prognosis: DSE is generally used for the diagnosis of CAD with ischemia, assessment of the risk of cardiac events, and prognosis. Risk stratification with normal DSE is associated with prognosis and compares favorably with that after normal myocardial SPECT imaging (thallium-201, technetium-99, or sestamibi).</p>
          <p>Compared to patients undergoing ESE, those undergoing DSE are generally older and have more comorbidities; wall motion and ejection fraction were identified on multivariate analysis as the best predictors of cardiac events.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
          <p>Reporting DSE results: the report should contain the data listed in <xref ref-type="table" rid="t42">Table 5.9</xref>.<sup><xref ref-type="bibr" rid="B38">38</xref></sup> Particular attention should be paid to the basal inferior and apical segments, which must be assessed on multiple images to prevent a false-positive finding of ischemia.</p>
          <table-wrap id="t42">
            <label>Table 5.9</label>
            <caption>
              <title>Recommendations for reporting results of dobutamine stress echocardiography<sup><xref ref-type="bibr" rid="B38">38</xref>,<xref ref-type="bibr" rid="B39">39</xref>,<xref ref-type="bibr" rid="B43">43</xref></sup></title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup width="100%">
                <col/>
              </colgroup>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="middle">Clinical information and indication for examination.</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle"><bold>Rest:</bold> Regional wall motion assessment.</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle">Wall motion: Number, location, and severity of regional (or global) abnormalities.</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle">2- Estimation of the ejection fraction.</td>
                </tr>
                <tr>
                  <td align="left" valign="middle"><bold>Stress:</bold> Regional wall motion assessment.</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">1- Wall motion: Number, location, and severity of regional (or global) abnormalities. 2- Estimation of the ejection fraction.</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">3- Assessment of regional wall motion should be repeated as many times as necessary.</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">4- If an ultrasound enhancement agent (contrast agent) is used, report the agent and dose administered.</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">Data on the stress testing protocol:</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">1- Doses of agent(s) for pharmacological stress.</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">2- Whether the target HR was achieved. HR and BP at each stage of the protocol.</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">3- Clinical and ECG findings during the examination, at rest and during stress.</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">4- Post-test echocardiographic findings.</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">5- Reason for test cessation (endpoint of protocol, ischemia, symptoms, or complications).</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
        </sec>
        <sec>
          <title>5.3. Assessment During DSE and in Recovery</title>
          <p>The development of regional wall motion abnormalities during the early stages of stress is indicative of severe coronary artery obstruction, with little or no myocardial perfusion reserve. At low doses, in the presence of moderate coronary obstruction with some myocardial reserve still preserved, increased blood flow leads to increased myocardial thickening and wall motion. At high doses, the combination of tachycardia and coronary obstruction results in a marked decline in subendocardial flow, with a corresponding decrease in regional wall motion.</p>
          <p>The persistence of wall motion abnormalities during the recovery period may be due to myocardial stunning, and is indicative of more severe ischemia. Late ischemic recovery imaging should be considered in patients with severe and extensive stress-induced. Most patients who present with abnormal DSE findings and subsequently undergo coronary angiography are found to have obstructive coronary artery disease.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
          <p>Extent and severity of regional wall motion abnormalities:</p>
          <p>Stress-induced hypoperfusion reflects the area of myocardium at risk, and its severity reflects the magnitude of wall motion abnormalities, which are exponentially correlated with increased adverse cardiovascular events.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
        </sec>
        <sec>
          <title>5.4. Transient Ischemic Dilatation of the Left Ventricle</title>
          <p>Patients with abnormal stress echocardiograms and transient ischemic dilatation of the LV have higher rates of multivessel disease and adverse cardiovascular events.</p>
          <p>Left bundle branch block (LBBB) - DSE can be used for detection of ischemia and risk stratification in patients with LBBB<sup><xref ref-type="bibr" rid="B3">3</xref></sup> (<xref ref-type="fig" rid="f45">Figure 5.3</xref>).</p>
          <fig id="f45">
            <label>Figure 5.3</label>
            <caption>
              <title>Dobutamine stress echocardiography, 2D echocardiography &#8211; left bundle branch block &#8211; Long axis: at rest &#8211; normal septum. Peak stress &#8211; slightly anomalous septum; immediate post-stress &#8211; highly anomalous septum.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <p>In a study of patients with LBBB who underwent both DSE and cine coronary angiography, Yanik et al.<sup><xref ref-type="bibr" rid="B44">44</xref></sup> observed good sensitivity, specificity, and accuracy of DSE for identifying ischemia: 82%, 95%, and 90% respectively in the left anterior descending (LAD) artery territory and 88%, 96%, and 93% in the circumflex and right coronary artery territories. Mairesse et al.,<sup><xref ref-type="bibr" rid="B45">45</xref></sup> in a similar study using DSE, myocardial perfusion imaging, and coronary angiography, found that DSE performed well in detecting ischemia in the LAD territory, with a sensitivity of 83%, specificity of 92%, and accuracy of 87%.</p>
          <p>Older adults &#8211; DSE is the first-line SE modality of choice for older adults, as well as for patients with musculoskeletal or neurological conditions that preclude exercise stress testing.<sup><xref ref-type="bibr" rid="B46">46</xref></sup> If the desired HR is not reached, isometric exercise to half-maximal strength for 3 to 4 minutes is recommended,<sup><xref ref-type="bibr" rid="B47">47</xref></sup> the patient should keep their mouth open and abdomen relaxed, to prevent an inadvertent vagal maneuver.</p>
        </sec>
        <sec>
          <title>5.5. Comparison with Other Imaging Modalities</title>
          <p>Large studies and meta-analyses have compared the predictive value of DSE and SPECT in different patient populations. The PROMISE study compared anatomical imaging using CT angiography versus functional imaging in 10,003 stable patients with symptoms suggestive of CAD; however, stress SPECT or DSE was performed in only 1,083 patients. None of these studies comparing the value of DSE versus other modalities considered the incremental value of ancillary findings detected by echocardiographic imaging performed at the time of stress echocardiography, including detection of non-ischemic causes of cardiac symptoms.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
          <p>DSE has diagnostic and prognostic accuracy similar to that of radionuclide stress perfusion imaging or cardiac magnetic resonance imaging.</p>
        </sec>
        <sec>
          <title>5.6. Value of a Negative DSE</title>
          <p>Samiei et al.<sup><xref ref-type="bibr" rid="B48">48</xref></sup> studied 705 patients with no prior history of CAD who had a negative ESE or DSE. They found that those who experienced events were older, diabetic, or hypertensive, and that results should be interpreted with greater caution due to the lower negative predictive value of DSE in these patients. The accuracy of diagnosis can also be significantly affected by the use of beta blockers, resulting in a false negative test.<sup><xref ref-type="bibr" rid="B43">43</xref>,<xref ref-type="bibr" rid="B49">49</xref></sup></p>
        </sec>
        <sec>
          <title>5.7. Complications of DSE</title>
          <p>According to a meta-analysis of 26 studies, complications occur in &lt; 0.1% of DSEs. The most common is arrhythmia, associated with significant ischemia and EF &lt; 35%. Atrial fibrillation and nonsustained ventricular arrhythmias occur in approximately 3% of patients. Frequent premature atrial or ventricular contractions occur in about 10% of cases. Sustained ventricular tachycardia is uncommon.<sup><xref ref-type="bibr" rid="B43">43</xref></sup> Angina and/or hypotension can occur due to midventricular obstruction or left ventricular outflow tract obstruction (the latter may lead to chest pain and arterial hypotension). Despite its safety, approximately 50% of patients undergoing DSE report some adverse reaction, with nausea, flushing, headache, neck or chest tightness, paresthesia, urinary urgency, dyspnea, and dry mouth being most common.<sup><xref ref-type="bibr" rid="B38">38</xref></sup></p>
          <p><xref ref-type="fig" rid="f46">Figure 5.4</xref> shows a dobutamine stress echocardiogram, incorporating three-dimensional imaging, positive for inducible myocardial ischemia in the septal region.</p>
          <fig id="f46">
            <label>Figure 5.4</label>
            <caption>
              <title>3D echocardiography &#8211; Short axis: at rest &#8211; normal septum. 3D echocardiography &#8211; Short axis: peak stress &#8211; akinetic septum.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
        </sec>
      </sec>
      <sec>
        <title>6. Dipyridamole Stress Echocardiography</title>
        <p>Dipyridamole is a pharmacological myocardial stressor that causes a buildup of endogenous adenosine, which then stimulates A2A receptors in the coronary arterioles.<sup><xref ref-type="bibr" rid="B50">50</xref></sup> It causes a 4- to 5-fold increase in coronary and myocardial blood flow from baseline without significantly increasing the heart rate or systolic volume, while simultaneously reducing systolic blood pressure.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Thus, in the presence of critical epicardial stenosis or microcirculatory dysfunction, administration of dipyridamole leads to heterogeneity in blood flow between stenotic segments and normal coronary arteries.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> The resulting mismatch in supply and demand leads to a reduction in subendocardial blood flow in regions supplied by stenosed arteries, a phenomenon known as coronary steal.<sup><xref ref-type="bibr" rid="B51">51</xref></sup></p>
        <p>The indications, types of equipment required, patient preparation, stages of the procedure, image acquisition, informed consent, and types of myocardial response are similar to those described above for dobutamine.</p>
        <sec>
          <title>6.1. Protocols</title>
          <p>There are 2 standard protocols for administering dipyridamole:</p>
          <list list-type="order">
            <list-item>
              <p>
                <bold>Two-infusion protocol:</bold>
              </p>
              <p>Intravenous infusion at 0.84 mg/kg over 10 min, in two separate infusions: 0.56 mg/kg over 4 min, followed by 4 min of observation with no medication; if the test is still negative, an additional 0.28 mg/kg of dipyridamole is administered over 2 minutes. If no endpoint (in this case, ischemia) is reached, 0.25 mg of atropine is administered every minute to a maximum total dose of 1 mg (<xref ref-type="fig" rid="f47">Figure 6.1</xref>).</p>
            </list-item>
            <list-item>
              <p>
                <bold>Accelerated protocol:</bold>
              </p>
              <p>Intravenous infusion at 0.84 mg/kg over 6 minutes, followed by a 4-minute observation period with no medication; administration of atropine at the end of the test is not necessary (<xref ref-type="fig" rid="f48">Figure 6.2</xref>).</p>
              <p>Aminophylline - With both protocols, aminophylline should be available for immediate administration in case of any dipyridamole-related adverse event and should be routinely infused at the end of the test, regardless of outcome,<sup><xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B50">50</xref></sup> due to the prolonged half-life of dipyridamole.</p>
              <p>Mechanism of Action and Pharmacokinetics: Dipyridamole works by inhibiting reuptake of endogenous adenosine. The alpha half-life of dipyridamole (i.e., the initial decline after peak concentration) is approximately 30 to 45 minutes. The beta half-life (the terminal decline in plasma concentration) is approximately 10 hours. Dipyridamole is metabolized in the liver by glucuronidation and excreted in bile.<sup><xref ref-type="bibr" rid="B52">52</xref>,<xref ref-type="bibr" rid="B53">53</xref></sup> Due to its vasodilating effect, it may cause a precipitous decline in blood pressure and a slight increase in heart rate.</p>
            </list-item>
          </list>
          <fig id="f47">
            <label>Figure 6.1</label>
            <caption>
              <title>Standard (stepwise) high-dose dipyridamole + atropine protocol.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <fig id="f48">
            <label>Figure 6.2</label>
            <caption>
              <title>Accelerated high-dose dipyridamole protocol.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
        </sec>
        <sec>
          <title>6.2. Adverse Effects</title>
          <p>The major adverse effects of dipyridamole include onset of atrioventricular (AV) block, potentially progressing to complete heart block, although to a lesser degree than that observed with adenosine (2%); chest pain (in about 20% of patients), which is nonspecific and not necessarily indicative of the presence of CAD; and minor side effects including headache, dizziness, nausea, hypotension, and flushing.<sup><xref ref-type="bibr" rid="B52">52</xref></sup></p>
        </sec>
        <sec>
          <title>6.3. Contraindications</title>
          <p>The main contraindications to dipyridamole stress echocardiography (<xref ref-type="table" rid="t43">Table 6.1</xref>) include: bronchospastic lung disease with continuous wheezing or a history of significant reactive airway disease, uncontrolled hypertension (SBP &gt; 200 mm Hg or DBP &gt; 110 mm Hg), hypotension (SBP &lt; 90 mm Hg), known hypersensitivity to dipyridamole, caffeine intake in the last 24 hours, and second- or third-degree AV block without a functioning pacemaker.<sup><xref ref-type="bibr" rid="B52">52</xref></sup> As with other SE protocols, the presence of unstable angina or complicated acute coronary syndrome, complex cardiac arrhythmias, symptomatic severe aortic stenosis, and hypertrophic cardiomyopathy with LVOTO are also absolute contraindications.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
          <table-wrap id="t43">
            <label>Table 6.1</label>
            <caption>
              <title>Contraindications to dipyridamole stress echocardiography</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 style="background-color:#76B4CF">
                  <th align="center" valign="middle">Contraindications applicable to all protocols</th>
                  <th align="center" valign="middle">Contraindications specific to dipyridamole stress echo</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="center" valign="middle">Unstable angina</td>
                  <td align="center" valign="middle">Bronchospastic lung disease with continuous wheezing</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="center" valign="middle">Acute or complicated coronary syndrome</td>
                  <td align="center" valign="middle">History of significant reactive airway disease</td>
                </tr>
                <tr>
                  <td align="center" valign="middle">Complex cardiac arrhythmia<break/> Decompensated heart failure</td>
                  <td align="center" valign="middle">Second- or third-degree AV block without a functioning pacemaker</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="center" valign="middle">Severe, symptomatic aortic stenosis</td>
                  <td align="center" valign="middle">SBP &lt; 90 mm Hg</td>
                </tr>
                <tr>
                  <td align="center" valign="middle">Hypertrophic cardiomyopathy and left ventricular outflow tract obstruction</td>
                  <td align="center" valign="middle">Known hypersensitivity to dipyridamole</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="center" valign="middle"/>
                  <td align="center" valign="middle">Caffeine intake in the last 24 hours</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
        </sec>
        <sec>
          <title>6.4. Coronary Flow Reserve</title>
          <p>Pharmacological stress with dipyridamole is the safest, simplest, and most suitable method for combined assessment of coronary flow reserve and regional wall motion/myocardial thickening.<sup><xref ref-type="bibr" rid="B50">50</xref></sup> However, individual patient characteristics, the local cost of the medication, and examiner preference should be taken into consideration when choosing one modality over another. For example, in patients with severe hypertension and/or a history of significant atrial or ventricular arrhythmias, dipyridamole may be the more appropriate choice.</p>
        </sec>
        <sec>
          <title>6.5. Accuracy</title>
          <p>Pharmacological stress testing with dipyridamole (accelerated protocol or standard protocol with atropine), when compared to dobutamine/atropine, has high diagnostic accuracy, similar to that of maximal treadmill exercise stress echocardiography, with lower sensitivity and higher specificity. Furthermore, dipyridamole/atropine stress echocardiography can overcome the effects of concomitant beta blocker therapy, achieving high heart rates and comparable diagnostic value.<sup><xref ref-type="bibr" rid="B54">54</xref></sup> Nevertheless, due to their cardioprotective effect, when beta-blockers are not discontinued before the examination, they may also lead to a false-negative result.</p>
          <p>Several meta-analyses have compared the accuracy of perfusion imaging to that of stress echocardiography.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> The two have been found similarly sensitive for detecting CAD, but stress echocardiography has greater specificity. For the detection of LMCA disease or multivessel CAD, stress echocardiography showed greater sensitivity compared to nuclear myocardial perfusion imaging, which compares relative differences in perfusion and may thus miss balanced or global ischemia.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B55">55</xref>-<xref ref-type="bibr" rid="B57">57</xref></sup></p>
        </sec>
      </sec>
      <sec>
        <title>7. Adenosine or Regadenoson Stress Echocardiography</title>
        <p>Adenosine is a purine present in all body tissues,<sup><xref ref-type="bibr" rid="B58">58</xref>,<xref ref-type="bibr" rid="B59">59</xref></sup> derived from adenine nucleotides and degradation of ATP. It is metabolized just as easily as it is generated, making its levels highly variable.<sup><xref ref-type="bibr" rid="B58">58</xref>,<xref ref-type="bibr" rid="B60">60</xref>,<xref ref-type="bibr" rid="B61">61</xref></sup> Its action is mediated through four transmembrane receptors: the A1, A2A, A2B, and A3 adenosine receptors.<sup><xref ref-type="bibr" rid="B58">58</xref>,<xref ref-type="bibr" rid="B59">59</xref>,<xref ref-type="bibr" rid="B62">62</xref></sup> All are G protein-coupled receptors (GPCRs),<sup><xref ref-type="bibr" rid="B59">59</xref></sup> with A1 and A3 receptors binding to inhibitory G proteins and A2 receptors binding to stimulatory G proteins.<sup><xref ref-type="bibr" rid="B59">59</xref>-<xref ref-type="bibr" rid="B61">61</xref></sup> This means they recruit distinct pathways through adenosine binding.<sup><xref ref-type="bibr" rid="B58">58</xref>-<xref ref-type="bibr" rid="B73">73</xref></sup> The adenosine receptors can thus be divided into two main subtypes: A1 and A3 receptors, which inhibit the enzyme adenylate cyclase, and A2 receptors, which stimulate adenylate cyclase. A1 receptors predominate in the myocardium, while A2 receptors are found in the coronary arteries (endothelial and smooth muscle cells). Therefore, activation of A2A receptors dilates the coronary arteries, causing hyperemia and increasing coronary blood load. Activation of A2A receptors in the presence of critical coronary stenosis plays a key role in inappropriate vasodilation and subendocardial ischemia, leading to vertical and horizontal steal phenomena and regional wall motion abnormalities. These effects are also present in a dipyridamole stress test.</p>
        <p>Intravenous infusion of adenosine or an intracoronary bolus of adenosine induces maximum flow (hyperemia). Under physiological conditions, the epicardial coronary artery exhibits laminar flow and little or no pressure gradient from proximal to distal. Coronary stenosis induces flow acceleration at the site of obstruction and can decrease pressure distal to lesions at rest, limiting hyperemia flow acceleration and causing an additional decrease in post-stenotic pressure during stress.<sup><xref ref-type="bibr" rid="B22">22</xref></sup></p>
        <p>Under normal physiological conditions, myocardial perfusion is autoregulated by pre-arterioles in the epicardium and arterioles within the myocardium, such that microvascular tone contributes to the majority of coronary resistance. Pathological microvascular conditions, including perivascular fibrosis (hypertension,<sup><xref ref-type="bibr" rid="B64">64</xref></sup> coronary artery disease,<sup><xref ref-type="bibr" rid="B65">65</xref></sup> myocardial hypertrophy, diabetes mellitus, status post heart transplantation, etc.), can cause microvascular angina by increasing microvascular tone at rest and/or limiting vasodilation during stress.</p>
        <p>Therefore, the use of vasodilators to induce stress seems justified in non-invasive functional tests. To optimize the ischemic effect and assess changes in regional wall motion, higher doses are required than those needed for perfusion imaging. Therefore, the protocols used in the SE laboratory must adopt higher and faster doses of vasodilator compared to perfusion imaging, resulting in distinct protocols.</p>
        <p>The cardiovascular effects of exogenous adenosine administered intravenously in humans are vagal inhibition and increased heart rate at low doses, while at high doses it can cause inhibition of the sinoatrial node and atrioventricular conduction, bradycardia, atrioventricular block, sympathetic stimulation, vasodilation in all arteriolar beds (except the renal pre-glomerular arterioles, where it promotes vasoconstriction), and hyperventilation, which is explained by interaction with carotid chemoreceptors.</p>
        <sec>
          <title>7.1. Use During Stress Echocardiography</title>
          <p>Intravenous infusion of adenosine causes a slight increase in heart rate and cardiac output and a slight decrease in systemic pressure (similar to dipyridamole). Mild tachycardia occurs despite the direct negative chronotropic and dromotropic effects of adenosine due to stimulation of myocardial A1 receptors, either by direct stimulation of sympathetic excitatory arterial chemoreceptors<sup><xref ref-type="bibr" rid="B67">67</xref></sup> or, indirectly, through systemic vasodilation (<xref ref-type="fig" rid="f49">Figure 7.1</xref>).</p>
          <fig id="f49">
            <label>Figure 7.1</label>
            <caption>
              <title>The use of adenosine in stress echocardiography demonstrates the major contribution of the vasodilatory effect in increasing coronary flow reserve (CFR), with a progressive, significant increase during the examination seen after 1 minute 23 seconds of adenosine infusion. The CFR increased from 16 cm/s at rest to 42 cm/s.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <p>In normal individuals, coronary blood flow increases four to five times from baseline after administration of adenosine, an increase comparable to that caused by high-dose of dipyridamole and substantially greater than that induced by exercise or dobutamine, during which coronary blood flow increases about three times the baseline value.<sup><xref ref-type="bibr" rid="B67">67</xref></sup> The maximum coronary dilating effect is achieved within 2 minutes following adenosine administration and wears off rapidly, within 2&#8211;5 minutes after the infusion is stopped.<sup><xref ref-type="bibr" rid="B68">68</xref></sup></p>
          <p>Regadenoson theoretically has attractive features which make it close to the "ideal" agent: rapid onset of action, adequate duration of effect that allows image acquisition, and fewer side effects. The reason for this is its selective stimulation of the A2A receptors specifically responsible for coronary vasodilation, avoiding the undesirable effects of stimulation of A1, A2B, and A3 receptors (such as dyspnea, headache, and flushing). The incidence of these side effects is not substantially reduced when compared to that seen with adenosine, although their severity is decreased.<sup><xref ref-type="bibr" rid="B69">69</xref></sup></p>
          <sec>
            <title>7.1.1. Indications</title>
            <p>The primary indication for adenosine/regadenoson stress testing is the detection of both epicardial and microvascular coronary artery disease causing myocardial ischemia. Like dipyridamole, it can also be used to assess myocardial viability, but with lower reproducibility compared to dobutamine.</p>
            <p>The longstanding safety record and short half-life of adenosine make it especially suitable for patients with severe aortic stenosis,<sup><xref ref-type="bibr" rid="B70">70</xref>,<xref ref-type="bibr" rid="B71">71</xref></sup> in the postoperative period of asymptomatic children who have undergone arterial switch surgery for transposition of the great arteries,<sup><xref ref-type="bibr" rid="B72">72</xref></sup> or older adults,<sup><xref ref-type="bibr" rid="B73">73</xref></sup> who may be especially vulnerable to complications during dipyridamole or dobutamine stress.</p>
            <p>One possibly emerging application of regadenoson is in patients with moderate-to-severe chronic obstructive pulmonary disease who are candidates for stress imaging and wish to avoid adenosine-induced bronchoconstriction and resulting respiratory compromise,<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B74">74</xref>,<xref ref-type="bibr" rid="B75">75</xref></sup> although in these patients the use of dobutamine may be more reasonable.</p>
          </sec>
        </sec>
        <sec>
          <title>7.2. Protocol for Adenosine Stress Echocardiography</title>
          <p>A dose of 140 &#956;g/kg/minute infused over 6 minutes is routinely recommended for myocardial ischemia. Increasing the dose to 160 and 210 &#956;g/kg/minute may be advised if the test is negative at the 140 &#956;g/kg/minute step; this is only necessary in 16&#8211;18% of cases.<sup><xref ref-type="bibr" rid="B68">68</xref>,<xref ref-type="bibr" rid="B76">76</xref>,<xref ref-type="bibr" rid="B77">77</xref></sup> When side effects are intolerable, the dose may also be titrated down. Atropine or handgrip exercise can be used to potentiate the test. As is routine in any stress test, continuous ECG, blood pressure, and, in this case, pulse oximetry monitoring is mandatory.</p>
          <p>Standardized images targeting all coronary territories (apical 4-chamber, 2-chamber, and 3-chamber views or parasternal long-axis, transverse LV, apical 4-chamber and 2-chamber views) should be acquired at rest, in an intermediate stage at 2 minutes of infusion, before the end of the infusion, and during the recovery phase.</p>
          <p>To assess coronary flow reserve in the LAD, the maximum diastolic velocity of mid-distal flow is recorded at rest, during maximal hyperemia (which typically occurs within 90 to 120 seconds of infusion), and before the end of the infusion.</p>
          <p>A dose of 100 &#956;g/kg/minute infused over 2 minutes can be used for the assessment of myocardial viability.</p>
        </sec>
        <sec>
          <title>7.3. Protocol for Regadenoson Stress Echocardiography</title>
          <p>Currently, regadenoson is administered as a 0.4 mg bolus in 5 mL of solution (without weight-based dose adjustment) injected over 10 seconds, followed by a 5 mL saline flush to ensure proper drug delivery. The optimal time for acquiring perfusion images is 2 to 10 minutes after drug infusion. Regadenoson allows combined assessment of myocardial perfusion imaging and regional wall motion analysis, and is most commonly used in the United States and the United Kingdom. Atropine can be used as an adjunct to potentiate stress.<sup><xref ref-type="bibr" rid="B78">78</xref></sup></p>
        </sec>
        <sec>
          <title>7.4. Contraindications</title>
          <p>Absolute contraindications include hypotension and severe airway obstruction, active bronchospasm, and second- or third-degree AV block (unless protected by a pacemaker). Use of these agents should be avoided in patients with signs or symptoms of unstable angina or cardiovascular instability.<sup><xref ref-type="bibr" rid="B75">75</xref></sup></p>
          <p>Patient preparation before stress echocardiography: Antianginal drugs and xanthine-containing products &#8211; including beverages such as coffee, teas, yerba mate, chocolate, soft drinks, and even foods such as bananas &#8211; decrease the sensitivity of adenosine SE, and should therefore be avoided starting 24 hours before the stresstest.</p>
        </sec>
        <sec>
          <title>7.5. Adverse Effects</title>
          <p>Adverse effects are not infrequent and can be limiting in a significant number of patients &#8211; up to 20%.<sup><xref ref-type="bibr" rid="B79">79</xref></sup> The most frequent limiting adverse effects of adenosine-mediated vasodilator stressors include shortness of breath, flushing, headache, hypotension, intolerable chest pain (sometimes unrelated to underlying ischemia, possibly induced by direct stimulation of myocardial A1 adenosine receptors), and high-degree AV block. First- or second-degree AV block occurs in 2% of tests, hypotension below 90 mm Hg in 3%, and severe bronchospasm in 0.1%.<sup><xref ref-type="bibr" rid="B80">80</xref>,<xref ref-type="bibr" rid="B81">81</xref></sup> Minor side effects, such as a feeling of warmth, flushing, headache, and nausea, occur in 80&#8211;84% of tests.<sup><xref ref-type="bibr" rid="B81">81</xref></sup> Hemodynamically significant decrease in systolic blood pressure (&gt; 20 mm Hg) is more likely in patients with severe aortic stenosis.<sup><xref ref-type="bibr" rid="B82">82</xref></sup> Exogenous adenosine has an even more pronounced negative chronotropic and dromotropic effect than endogenous adenosine,<sup><xref ref-type="bibr" rid="B83">83</xref></sup> making the onset of advanced AV blocks more frequent with adenosine than with dipyridamole or adenosine triphosphate at equivalent doses. Most reactions to adenosine resolve within 1 to 5 minutes. On very rare occasions, aminophylline infusion is required.</p>
        </sec>
        <sec>
          <title>7.6. Diagnostic Accuracy</title>
          <p>Based on a published meta-analysis of 11 studies, adenosine stress echocardiography had the same sensitivity (79%), specificity (91.5%), and accuracy for detection of regional wall motion abnormalities as exercise stress echocardiography, dipyridamole echocardiography, and dobutamine echocardiography, with superior specificity compared to SPECT stress imaging.<sup><xref ref-type="bibr" rid="B84">84</xref></sup></p>
        </sec>
      </sec>
      <sec>
        <title>8. Other Stress Echocardiography Modalities: Pacing, Ergonovine, Handgrip, and Hyperventilation</title>
        <sec>
          <title>8.1. Pacing Stress Echocardiography</title>
          <p>In patients with contraindications to physical or pharmacological stress, pacing stress echocardiography (PASE) by transesophageal atrial pacing may be an alternative. Stimulation is performed by an external pacemaker connected to a bipolar esophageal electrode and a recording catheter protected by a 10F sheath, introduced transnasally or transorally under topical anesthesia. The lowest current capable of providing stable capture is used, starting at 10 bpm above the resting heart rate and increasing by 20 bpm every 2 minutes up to 85% of the predicted maximum heart rate for age.<sup><xref ref-type="bibr" rid="B85">85</xref></sup> he criteria for test cessation are intolerable symptoms, significant arrhythmia, ECG with ST segment depression &#8805; 2 mm at 80 ms after the J point, SBP &gt; 220 mm Hg, DBP &gt; 110 mm Hg, or SBP &lt; 90 mm Hg. Serious adverse events are rare. Second-degree Wenckebach-type AV block may occur. Compared to dobutamine stress, PASE was associated with less hypotension or hypertension, arrhythmias, or limiting symptoms; shorter duration and recovery times; and more frequent achievement of the target heart rate. There was excellent agreement between the two methods for assessment of regional wall motion.<sup><xref ref-type="bibr" rid="B85">85</xref></sup> In patients with a permanent pacemaker in place, stress can be achieved through noninvasive programming.<sup><xref ref-type="bibr" rid="B86">86</xref></sup> The target is 85% of the maximum heart rate or until signs of ischemia develop. PASE demonstrated a sensitivity of 70%, specificity of 90%, and accuracy of 78% for diagnosis of obstructive CAD, and was an independent predictor of all-cause mortality.</p>
        </sec>
        <sec>
          <title>8.2. Addition of Handgrip Exercise to Stress Echocardiography</title>
          <p>Isometric handgrip exercise produces a slight increase in HR and oxygen consumption compared to isotonic exercise. However, it produces a sudden and more significant increase in blood pressure. Using a hand dynamometer, a submaximal protocol (25&#8211;50% of maximum grip strength) can be maintained for 3-4 minutes.<sup><xref ref-type="bibr" rid="B87">87</xref></sup> Isometric exercise has low sensitivity on its own for investigation of obstructive CAD, but is useful when combined with pharmacological stress.<sup><xref ref-type="bibr" rid="B88">88</xref></sup> When combined with longitudinal strain assessment, it showed a sensitivity of 80%, specificity of 66%, and AUC of 0.77 for diagnosis of myocardial ischemia.<sup><xref ref-type="bibr" rid="B89">89</xref></sup> It has also been used as an alternative to the cycle ergometer for diastolic stress testing for diagnosis of HFpEF. It also has an advantage over the cycle ergometer regarding motion artifacts. A submaximal test with 40% of maximum handgrip for 3&#8211;5 minutes produces O<sub>2</sub> consumption similar to low-load (20 W) cycle ergometer exercise, with a comparable increase in E/e&#8217; ratio.<sup><xref ref-type="bibr" rid="B90">90</xref></sup></p>
        </sec>
        <sec>
          <title>8.3. Ergonovine and Hyperventilation Stress Echocardiography</title>
          <p>Ergonovine has been used for vasoconstrictive stress testing. The protocol consists of administration of an intravenous bolus (0.025 to 0.05 mg) every 5 minutes until evidence of ischemia is present or a total dose of 0.35 mg is reached. Its main indication is the diagnosis of vasospastic angina, with a sensitivity of around 91% and a specificity of around 88%. In a study of 3,094 patients, ergonovine stress was positive in 8.6%. There were no documented cases of myocardial infarction or death. However, 0.6% of patients had transient symptoms, and one patient experienced sudden death but was successfully resuscitated. This modality demonstrated prognostic value for major adverse cardiac events.<sup><xref ref-type="bibr" rid="B91">91</xref></sup> Another form of stress used to diagnose vasospastic angina is hyperventilation, with or without cold water immersion. The test consists of a period of hyperventilation with deep breathing at 30 breaths per minute for 6 minutes, followed by immersion of the patient's hand in ice water for 2 minutes. ECG monitoring and echocardiography are performed during the stress period and 15 minutes after its completion. The criteria for cessation are the presence of chest pain and ST elevation &gt;1 mm in at least two leads. Onset of a new regional wall motion abnormality during stress is diagnostic of vasospasm. When compared to intracoronary acetylcholine injection during angiography, this method showed a sensitivity of around 91%, specificity of 90%, and accuracy of 91%.<sup><xref ref-type="bibr" rid="B92">92</xref>,<xref ref-type="bibr" rid="B93">93</xref></sup></p>
        </sec>
      </sec>
      <sec>
        <title>9. Diastolic Stress Echocardiography</title>
        <p>Heart failure with preserved ejection fraction (HFpEF) is a major public health problem worldwide due to population aging with an increased prevalence of comorbidities. The most common clinical manifestation of HFpEF is dyspnea on exertion.<sup><xref ref-type="bibr" rid="B94">94</xref>,<xref ref-type="bibr" rid="B95">95</xref></sup> Diagnosis is challenging in patients who only present symptoms during exercise, as natriuretic peptides, cardiac output (CO), and left ventricular filling pressure (LVFP) may all be normal or only slightly abnormal compared to individuals with normal diastolic function (DF). In these cases, the increase in LVFP becomes evident only during exercise, highlighting the importance of stress testing.<sup><xref ref-type="bibr" rid="B94">94</xref>,<xref ref-type="bibr" rid="B95">95</xref></sup> Diastolic SE is a modality capable of providing information in these questionable cases, using parameters obtained from assessment of left ventricular dysfunction at rest and during exercise.<sup><xref ref-type="bibr" rid="B96">96</xref>-<xref ref-type="bibr" rid="B98">98</xref></sup></p>
        <sec>
          <title>9.1. Normal and Abnormal Response to Exercise of Diastolic Function</title>
          <p>Normal DF allows for adequate LV filling at rest and during exercise, with increased CO and no elevation of LVFP. The most commonly studied parameters are the ratio of the peak early mitral filling velocity (E) to the early diastolic mitral annular velocity (e&#8217;) obtained by tissue Doppler imaging at rest and during exertion. In normal relaxation, during exercise, there is a proportional increase in these velocities, with the E/e&#8217; ratio remaining unchanged.<sup><xref ref-type="bibr" rid="B96">96</xref>,<xref ref-type="bibr" rid="B97">97</xref></sup> In patients with myocardial disease and abnormal relaxation, there is no increase in e&#8217; as there is in E, and an increase in the E/e&#8217; ratio is expected. E/e&#8217; values &lt; 10 during exercise suggest normal LVFP, whereas values &gt; 14 (average e&#8217;) or &gt; 15 (using septal e&#8217; alone) suggest increased LVFP. Estimating pulmonary artery systolic pressure (PASP) using peak tricuspid regurgitation velocity (TRV) at rest and during exercise is also useful, as PASP increases with increasing LVFP.<sup><xref ref-type="bibr" rid="B94">94</xref>,<xref ref-type="bibr" rid="B97">97</xref></sup></p>
        </sec>
        <sec>
          <title>9.2. Indications for Stress Echocardiography</title>
          <p>For patients with HFpEF and dyspnea on exertion, assessment at rest may be insufficient, thus justifying stress testing to induce an increase in LVFP.<sup><xref ref-type="bibr" rid="B94">94</xref>,<xref ref-type="bibr" rid="B97">97</xref></sup> Guidelines from different societies suggest diastolic SE in suspected clinical signs of HFpEF.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B94">94</xref>,<xref ref-type="bibr" rid="B98">98</xref>,<xref ref-type="bibr" rid="B99">99</xref></sup> <xref ref-type="fig" rid="f50">Figure 9.1</xref> illustrates the recommendations.</p>
          <fig id="f50">
            <label>Figure 9.1</label>
            <caption>
              <title>Indications for diastolic stress echocardiography according to current guidelines.<sup><xref ref-type="bibr" rid="B94">94</xref>,<xref ref-type="bibr" rid="B95">95</xref>,<xref ref-type="bibr" rid="B98">98</xref>,<xref ref-type="bibr" rid="B100">100</xref></sup></title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <p>HFA-PEFF score: suggested by the European Society of Cardiology for the diagnosis of HFpEF. H<sub>2</sub>FPEF score: cited in the U.S. guideline for diagnosis of HFpEF.</p>
        </sec>
        <sec>
          <title>9.3. Protocols Used in Diastolic Stress Echocardiography</title>
          <p>Diastolic SE can be performed using a stationary bicycle or treadmill, or on a reclining ergometer/echo couch. The reclining ergometer (echo couch) is the most suggested by evaluations of regional wall motion and DF during each stage and at peak stress.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B94">94</xref>,<xref ref-type="bibr" rid="B99">99</xref></sup> When a treadmill is used, regional wall motion can be assessed after exercise ceases (60-90 seconds later), followed by assessment of DF. In both modalities, patients are encouraged to reach the maximum HR predicted for age or continue until the onset of limiting symptoms. <xref ref-type="table" rid="t44">Tables 9.1</xref> and <xref ref-type="table" rid="t45">9.2</xref> show the advantages and limitations of the protocols and the variables which can be assessed<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B98">98</xref></sup> and the parameters acquired during diastolic stress echocardiography.</p>
          <table-wrap id="t44">
            <label>Table 9.1</label>
            <caption>
              <title>Protocols, advantages, and limitations</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 style="background-color:#76B4CF">
                  <th align="left" valign="middle">Modality</th>
                  <th align="center" valign="middle">Protocols</th>
                  <th align="center" valign="middle">Advantages</th>
                  <th align="center" valign="middle">Limitations</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="middle">Bicycle</td>
                  <td align="center" valign="middle">Standard: initial load 25 W, 60 rpm, 25-W increments every 2 or 3 minutes.</td>
                  <td align="center" valign="middle">- Physiological.<break/> - More time for acquisition.<break/> - Validated by more studies.</td>
                  <td align="center" valign="middle">- Limited availability.<break/> - Difficulty in obtaining images.<break/> - Lower workload achieved compared to treadmill.</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle">Treadmill</td>
                  <td align="center" valign="middle">Bruce: initial incline 10%, followed by 2% increments at each 3-minute stage. <break/>Modified Bruce: initial incline 0%, duration 3 minutes per stage, with gradually increasing incline.</td>
                  <td align="center" valign="middle">- Physiological.<break/> - Availability.<break/> - High workloads reached.<break/> - Higher double product at the expense of a higher HR.<break/> - More specific for detecting ischemia than bicycle.</td>
                  <td align="center" valign="middle">- Difficulty in obtaining images.<break/> - Possibility of normalization of post-exercise changes.<break/> - Wait until HR is &lt; 100-110/min in recovery (to avoid merging of Doppler flow waves).<break/> - No hemodynamic validation.</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN16">
                <p>W: Watts; rpm: revolutions per minute, HR: heart rate</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <table-wrap id="t45">
            <label>Table 9.2</label>
            <caption>
              <title>Parameters acquired during diastolic stress echocardiography at rest and during (bicycle) or immediately after (treadmill) exercise</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 style="background-color:#76B4CF">
                  <th align="left" valign="middle">Parameter</th>
                  <th align="center" valign="middle">Acquisition</th>
                  <th align="center" valign="middle">Advantages</th>
                  <th align="center" valign="middle">Limitations</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="middle">E</td>
                  <td align="center" valign="middle">- Apical 4-chamber.<break/> - Measure at peak early diastolic velocity.</td>
                  <td align="center" valign="middle">Feasible and reproducible.</td>
                  <td align="center" valign="middle">- The E and A velocity waves merge at high HR.<break/> - Decreases with age.<break/> - Acquire when HR is between 100 and 110 bpm.</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle">e' (lateral, medial)</td>
                  <td align="center" valign="middle">- Apical 4-chamber.<break/> - Tissue Doppler imaging of mitral annulus <break/>in the septal and lateral region.</td>
                  <td align="center" valign="middle">Feasible and reproducible.</td>
                  <td align="center" valign="middle">- The e' and a' velocity waves merge at high HR.<break/> - Decreases with age.<break/> - Limited accuracy in patients with mitral annulus calcification, prosthetic ring annuloplasty, pericardial disease.</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">E/e' ratio</td>
                  <td align="center" valign="middle">- Ratio between the E and e' velocities.</td>
                  <td align="center" valign="middle">Hemodynamically validated.</td>
                  <td align="center" valign="middle">- Decreased accuracy in normal individuals, mitral annulus calcification, significant mitral and pericardial disease, regional wall motion abnormalities.</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle">Peak TRV</td>
                  <td align="center" valign="middle">- Apical 4-chamber or parasternal RV inflow view.<break/> - Continuous Doppler.</td>
                  <td align="center" valign="middle">Indirect adjunct to estimation of LV filling pressure.</td>
                  <td align="center" valign="middle">- Increased velocity can occur due to illness or as a normal response to increased flow during exercise. <break/>- A full signal is not obtained in 1/3 of patients.<break/> - Less reliable if there is marked tricuspid regurgitation.</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN17">
                <p>LV: left ventricle; RV: right ventricle; E: peak early mitral filling velocity; A: late left ventricular filling velocity by atrial systole; e&#8217;: early diastolic mitral annular velocity obtained by tissue Doppler imaging; HR: heart rate; bpm: beats per minute.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec sec-type="discussion">
          <title>9.4. Interpretation of Diastolic Stress Echocardiography</title>
          <p>Functional capacity should be compared to that expected for age and sex.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B94">94</xref>,<xref ref-type="bibr" rid="B99">99</xref></sup> <xref ref-type="table" rid="t46">Table 9.3</xref> illustrates normal and abnormal responses to diastolic SE.</p>
          <table-wrap id="t46">
            <label>Table 9.3</label>
            <caption>
              <title>Possible echocardiographic findings at diastolic stress echocardiography</title>
            </caption>
            <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 style="background-color:#76B4CF">
                  <th align="left" valign="middle"/>
                  <th align="center" valign="middle" colspan="2">Diastolic SE in normal diastolic function</th>
                  <th align="center" valign="middle" colspan="2">Diastolic SE in diastolic dysfunction</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="middle"/>
                  <td align="center" valign="middle">Pre-exercise</td>
                  <td align="center" valign="middle">During or immediately after exercise</td>
                  <td align="center" valign="middle">Pre-exercise<xref ref-type="table-fn" rid="TFN19">**</xref></td>
                  <td align="center" valign="middle">During or immediately after exercise</td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle">Septal E/e' (average)</td>
                  <td align="center" valign="middle">&lt; 10</td>
                  <td align="center" valign="middle">&lt; 10</td>
                  <td align="center" valign="middle">&lt; 14</td>
                  <td align="center" valign="middle">&gt; 15 (&gt;14)</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">Peak TRV<xref ref-type="table-fn" rid="TFN18">*</xref> (m/s)</td>
                  <td align="center" valign="middle">&lt; 2.8</td>
                  <td align="center" valign="middle">&lt; 2.8</td>
                  <td align="center" valign="middle">&lt; 2.8</td>
                  <td align="center" valign="middle">&gt; 2.8 / &gt;3,4</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN18">
                <label>*</label>
                <p>Peak TRV values vary across guidelines. According to ASE/EACVI, it is considered abnormal if &gt; 2,8 m/s (higher sensitivity), whereas according to HFA/ESC, it is abnormal if &gt; 3.4 m/s (higher specificity).<sup><xref ref-type="bibr" rid="B94">94</xref>,<xref ref-type="bibr" rid="B99">99</xref></sup></p>
              </fn>
              <fn id="TFN19">
                <label>**</label>
                <p>In abnormal diastolic SE, the septal e&#8217; velocities at rest should be &lt; 7 cm/s, or, if only the lateral e&#8217; is evaluated, it should be &lt; 10 cm/s.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>Diastolic SE is important for detecting changes that are not present at rest and only appear during physical exertion, and current guidelines recommend its use to identify patients with HFpEF.</p>
        </sec>
      </sec>
      <sec>
        <title>10. Stress Echocardiography in MINOCA (Myocardial Infarction with Nonobstructive Coronary Arteries) and in Microvascular Disease</title>
        <p>MINOCA (myocardial infarction with nonobstructive coronary arteries) encompasses those cases of acute coronary syndrome (ACS) with troponin levels elevated above the 99th percentile, symptoms, or abnormal ECG findings in the absence of epicardial coronary artery obstructions &gt; 50%.<sup><xref ref-type="bibr" rid="B101">101</xref></sup> MINOCA accounts for approximately 5-10% of ACS cases.<sup><xref ref-type="bibr" rid="B101">101</xref>,<xref ref-type="bibr" rid="B102">102</xref></sup> The prognosis for patients with MINOCA is variable and depends on the underlying mechanism.<sup><xref ref-type="bibr" rid="B101">101</xref></sup> This condition is more prevalent in younger individuals, particularly females, and conventional coronary heart disease risk factors such as dyslipidemia, smoking, and family history have a reduced prevalence.<sup><xref ref-type="bibr" rid="B103">103</xref>,<xref ref-type="bibr" rid="B104">104</xref></sup> Identifying MINOCA and ruling out potential differential diagnoses is extremely important for appropriate and early clinical management.<sup><xref ref-type="bibr" rid="B104">104</xref></sup></p>
        <sec>
          <title>10.1. Pathophysiology</title>
          <p>Currently, MINOCA is classified into 2 types:<sup><xref ref-type="bibr" rid="B103">103</xref>,<xref ref-type="bibr" rid="B104">104</xref></sup></p>
          <list list-type="bullet">
            <list-item>
              <p>Type I: Plaque-related events: rupture, erosion, and dissection of the coronary artery wall;</p>
            </list-item>
            <list-item>
              <p>Type II: Imbalance between oxygen supply and consumption, which can occur in coronary spasm, coronary embolism, endothelial dysfunction, anemia, hypertension, hypotension, extremes of heart rate, hypoxemia, etc.</p>
            </list-item>
          </list>
          <p>It is important to stress that conditions such as Takotsubo syndrome are not considered MINOCA, as they are not ischemic in nature. However, 10&#8211;29% of patients with Takotsubo syndrome have comorbid coronary artery disease.<sup><xref ref-type="bibr" rid="B104">104</xref></sup> Other differential diagnoses which must be considered and extensively investigated include myocarditis, sepsis-related changes, pulmonary embolism, and cardiac contusion. When ischemic causes are suspected, invasive hemodynamic assessment is necessary to detect the presence of significant coronary obstruction or occlusion of small secondary branches.<sup><xref ref-type="bibr" rid="B101">101</xref>-<xref ref-type="bibr" rid="B104">104</xref></sup></p>
        </sec>
        <sec sec-type="methods">
          <title>10.2. Main Diagnostic Methods in MINOCA</title>
          <p>The diagnostic workup begins with the typical presentation of chest pain and elevated troponin (&gt; 99<sup>th</sup> percentile, with a typical curve-like pattern), with or without abnormal ECG findings.<sup><xref ref-type="bibr" rid="B104">104</xref></sup> With the diagnosis of ACS established, the patient then undergoes coronary angiography, and the possibility of obstruction &#8805; 50% is ruled out after careful review of the images. Anatomical-functional diagnosis can be supplemented by the use of intracoronary ultrasound and optical coherence tomography, methods that allow analysis of plaque characteristics and detection of plaque rupture. Fractional flow reserve measurement can identify plaques that visually appear to cause &lt; 50% obstruction, but have significant repercussions nonetheless.<sup><xref ref-type="bibr" rid="B103">103</xref>-<xref ref-type="bibr" rid="B105">105</xref></sup></p>
          <p>Currently, CMR imaging is the modality of choice for evaluating patients with suspected MINOCA. This method provides an accurate differential diagnosis of clinical mimics of MINOCA. Liang et al.,<sup><xref ref-type="bibr" rid="B102">102</xref></sup> in a retrospective study in which CMR was used to reclassify over 800 patients originally diagnosed with MINOCA, found that only 27% of cases were actually MINOCA and 73% had other conditions, such as myocarditis.</p>
          <p><xref ref-type="fig" rid="f51">Figure 10.1</xref> illustrates the diagnostic algorithm that can be followed when MINOCA is suspected.</p>
          <fig id="f51">
            <label>Figure 10.1</label>
            <caption>
              <title>Algorithm for MINOCA diagnosis and/or stratification. ACS: acute coronary syndrome; TT Echo: transthoracic echocardiography; PE: pulmonary embolism; S.: syndrome; CMR: cardiac magnetic resonance imaging; OCT: optical coherence tomography; TE Echo: transesophageal echocardiography. Adapted from Del Buono et al.<sup><xref ref-type="bibr" rid="B107">107</xref></sup></title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <p>Pharmacological stress echocardiography plays a role in MINOCA by evaluating the absence of regional wall motion abnormalities or, more accurately, in cases of vasospasm, which can be diagnosed during the recovery phase of pharmacological stress tests with rapid infusion of beta blockers or aminophylline.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B106">106</xref></sup></p>
        </sec>
        <sec>
          <title>10.3. The Stress Echocardiogram in MINOCA</title>
          <p>The latest Brazilian Society of Cardiology Guidelines on Unstable Angina and Myocardial Infarction<sup><xref ref-type="bibr" rid="B103">103</xref></sup> contain a Class IIa recommendation for stress echocardiography in MINOCA of microvascular etiology for risk stratification purposes, as the presence of regional wall motion abnormalities carries a worse prognosis.</p>
          <p>The ischemic cascade in MINOCA exhibits a different behavior from that observed in epicardial disease, referred to as the alternative and classic ischemic cascade, respectively (<xref ref-type="fig" rid="f52">Figure 10.2</xref>). In the alternative cascade, the primary change is a reduction in coronary flow reserve. In this setting, the standard stress echocardiography protocol which only assesses regional wall motion has low sensitivity. Thus, the ABCDE protocol<sup><xref ref-type="bibr" rid="B106">106</xref></sup> is indicated to increase the accuracy of examination and allow risk stratification. This protocol comprises: assessment of ventricular volumes and regional wall motion abnormalities (A), lung ultrasound for B-lines (B) to investigate congestion in the four anterior thoracic segments, assessment of left ventricular contractile (C) reserve by calculating the ejection fraction using volumetric 2D echo, Doppler (D)-based assessment of coronary flow reserve in the left anterior descending artery, and ECG (E)-based assessment of chronotropic reserve.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> We strongly encourage use of the ABCDE protocol, as previously described in the aforementioned guideline.<sup><xref ref-type="bibr" rid="B106">106</xref></sup> Many of these patients report chest pain on examination, which does not occur at the end of the classic ischemic cascade, but rather at the start.</p>
          <fig id="f52">
            <label>Figure 10.2</label>
            <caption>
              <title>Comparison of the ischemic cascade in epicardial disease (classic) and in MINOCA (alternative). Adapted from Picano et al.<sup><xref ref-type="bibr" rid="B2">2</xref></sup></title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <p>Ultrasound enhancement agents can be used to evaluate left ventricular opacification and analyze the endocardial borders, as in epicardial coronary artery disease.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup> Use of these agents for analysis of coronary reserve in the ABCDE protocol and for assessment of myocardial perfusion is considered off-label, but can be useful at centers with appropriate expertise.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup></p>
          <p>It is worth noting that MINOCA is a diagnosis of exclusion in ACS, where stress echocardiography plays a diagnostic role primarily to assess microvascular disease and coronary spasm, combined with the ABCDE protocol to increase the sensitivity of the examination.</p>
        </sec>
      </sec>
      <sec>
        <title>11. Stress Echocardiography in Mitral Valve Disease</title>
        <p>SE &#8211; preferably using exercise stress &#8211; plays an important role in assisting with the refinement of severity diagnosis, prognostic stratification, and definition of treatment options in patients with mitral valve disease (MVD).<sup><xref ref-type="bibr" rid="B108">108</xref>,<xref ref-type="bibr" rid="B109">109</xref></sup> Physiological conditions and comorbid diseases can modify the clinical presentation and interfere with the accuracy of conventional diagnostic methods in assessing the severity of MVD, which is influenced by hemodynamic conditions such as preload, afterload, and heart rate. In some cases, there may be discordant severity criteria on echocardiography and symptoms may be difficult to assess (due to sociocultural aspects, cognitive changes, sedentary lifestyle, etc.), leading to what is known as "clinical-echocardiographic dissociation." In these patients, it is important to consider supplementing conventional echocardiography with other imaging methods, as well as with SE for functional assessment, to better define treatment goals.</p>
        <p>There are three core indications for SE in the evaluation of native mitral valve disease: 1) Severe asymptomatic MVD; 2) Non-severe symptomatic MVD; and 3) MVD with low transvalvular flow. Physical exercise (ESE) is the stress method most indicated for assessment of MVD, as it allows evaluation of exercise tolerance and emergent symptoms and the acquisition of hemodynamic data in a physiological setting (reproducible of activities of daily living), although dobutamine stress can also be used in cases of mitral stenosis (MS) and patients with limited exercise ability.<sup><xref ref-type="bibr" rid="B110">110</xref></sup> For ESE, either a treadmill, stationary bicycle/cycle ergometer, or reclining ergometer/echo couch can be used, with the latter having the advantage of allowing continuous echocardiographic imaging. This allows the echocardiographer to detect abnormalities at low workload (before peak exertion) and obtain data and images at peak exertion, which may be underestimated with the use of a treadmill because image capture is done after peak exertion.</p>
        <sec>
          <title>11.1. Mitral Stenosis</title>
          <p>Rheumatic MS remains a significant public health issue in Brazil and other developing countries, with a high incidence in Africa, some regions of Asia, and across Latin America.<sup><xref ref-type="bibr" rid="B111">111</xref>,<xref ref-type="bibr" rid="B112">112</xref></sup> It is still the most prevalent cause of MS worldwide, followed by degenerative diseases. The incidence of degenerative MS associated with mitral annular calcification increases with age, and is the predominant cause of MS in industrialized countries.<sup><xref ref-type="bibr" rid="B113">113</xref></sup></p>
          <p>SE has a well-validated indication for evaluating the severity and hemodynamic repercussions of MS, especially in patients who present with a discrepancy between the degree of stenosis determined by imaging methods and their clinical findings (clinical-echocardiographic dissociation).<sup><xref ref-type="bibr" rid="B108">108</xref>,<xref ref-type="bibr" rid="B114">114</xref>,<xref ref-type="bibr" rid="B115">115</xref></sup> Patients with moderate MS as quantified on resting echocardiography are often quite symptomatic on exertion, and SE may be able to demonstrate hemodynamic changes that justify these symptoms, such as a significant increase in transvalvular gradients and PASP (<xref ref-type="table" rid="t47">Table 11.1</xref>). Poor prognostic criteria include an absolute increase in mean gradient above 15 mm Hg with exertion<sup><xref ref-type="bibr" rid="B108">108</xref>,<xref ref-type="bibr" rid="B110">110</xref></sup> or an increase in PASP above 60 mm Hg.<sup><xref ref-type="bibr" rid="B116">116</xref></sup> Other situations in which SE may be useful in MS are in patients scheduled to undergo major surgery or patients who intend to become pregnant, to predict how the disease will behave in hemodynamically adverse situations.<sup><xref ref-type="bibr" rid="B117">117</xref></sup> In patients with exercise limitations, dobutamine stress echocardiography can be used, as it has been validated for this specific population, and, in this case, an absolute mean gradient value of 18 mmHg indicates a worse prognosis.<sup><xref ref-type="bibr" rid="B118">118</xref></sup> The risk of acute pulmonary edema and hemodynamic decompensation when these patients undergo SE must be taken into account.<sup><xref ref-type="bibr" rid="B118">118</xref></sup></p>
          <table-wrap id="t47">
            <label>Table 11.1</label>
            <caption>
              <title>Use of stress echocardiography in assessment of mitral valve disease<sup><xref ref-type="bibr" rid="B116">116</xref>,<xref ref-type="bibr" rid="B108">108</xref>,<xref ref-type="bibr" rid="B110">110</xref>,<xref ref-type="bibr" rid="B117">117</xref></sup></title>
            </caption>
            <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 style="background-color:#76B4CF">
                  <th align="left" valign="middle">Mitral valve condition</th>
                  <th align="center" valign="middle">Type of stress</th>
                  <th align="center" valign="middle">Guideline-established criteria</th>
                  <th align="center" valign="middle">Clinical trial-established criteria</th>
                  <th align="center" valign="middle">Parameters of interest</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="middle">Primary mitral regurgitation</td>
                  <td align="left" valign="middle">Physical activity</td>
                  <td align="left" valign="middle">-</td>
                  <td align="left" valign="middle">Exercise-induced increase in PASP &gt; 60 mm Hg<break/> Contractile reserve<break/> Exercise-induced increase in EROA &gt; 10 mm</td>
                  <td align="left" valign="middle">
                    <list list-type="bullet">
                      <list-item>
                        <p>Symptoms</p>
                      </list-item>
                      <list-item>
                        <p>Pressure response</p>
                      </list-item>
                      <list-item>
                        <p>Exercise-induced increase in PASP &gt; 60 mm Hg</p>
                      </list-item>
                      <list-item>
                        <p>New regional wall motion abnormalities</p>
                      </list-item>
                      <list-item>
                        <p>Exercise-induced increase in LVEF &lt; or &gt; 5%</p>
                      </list-item>
                      <list-item>
                        <p>Exercise-induced increase in GLS &lt; or &gt; 2%</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr style="background-color:#C7DFEC">
                  <td align="left" valign="middle">Mitral stenosis</td>
                  <td align="left" valign="middle">Physical activity (preferable)</td>
                  <td align="left" valign="middle">Mean transmitral gradient increase &gt; 15 mm Hg at peak exertion (or &gt; 18 mm Hg with dobutamine)</td>
                  <td align="left" valign="middle">PASP increase &gt; 60 mm Hg</td>
                  <td align="left" valign="middle">
                    <list list-type="bullet">
                      <list-item>
                        <p>Symptoms</p>
                      </list-item>
                      <list-item>
                        <p>Pressure response</p>
                      </list-item>
                      <list-item>
                        <p>Exercise-induced increase in PASP &gt; 60 mm Hg</p>
                      </list-item>
                      <list-item>
                        <p>New regional wall motion abnormalities</p>
                      </list-item>
                      <list-item>
                        <p>Exercise-induced decrease in LVEF</p>
                      </list-item>
                      <list-item>
                        <p>Mean transmitral gradient increase &gt; 15 mm Hg at peak exertion</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN20">
                <p>Adapted from Lancellotti et al.<sup><xref ref-type="bibr" rid="B116">116</xref></sup></p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>11.2. Mitral Regurgitation</title>
          <p>The main cause of mitral regurgitation (MR) in developed countries is degenerative mitral valve disease,<sup><xref ref-type="bibr" rid="B119">119</xref></sup> whereas in developing countries, rheumatic fever remains an important etiological factor and driver of morbidity and mortality.<sup><xref ref-type="bibr" rid="B120">120</xref></sup> Recent guidelines have established severity criteria for MR.<sup><xref ref-type="bibr" rid="B133">133</xref></sup> Echocardiography plays an important role in determining the optimal timing of intervention, especially in symptomatic patients, as well as in asymptomatic ones with significant ventricular remodeling, left ventricular dysfunction (LVEF &#8804; 60%), atrial fibrillation (AF), and/or pulmonary hypertension.<sup><xref ref-type="bibr" rid="B114">114</xref>,<xref ref-type="bibr" rid="B122">122</xref></sup></p>
          <p>Echocardiography plays a fundamental role in the evaluation of patients with MR, especially in those with discrepancies between clinical and echocardiographic findings, such as symptomatic patients with non-severe MR.<sup><xref ref-type="bibr" rid="B123">123</xref></sup> Stress testing has the added benefit of assessing the patient's functional capacity, not only clarifying the correlation between symptoms and hemodynamics but also stratifying risk in patients who are reportedly asymptomatic despite severe MR. Symptomatic patients with apparently non-severe MR on baseline echocardiography may have dynamic mechanisms in play that become clearer during SE.<sup><xref ref-type="bibr" rid="B124">124</xref></sup> Therefore, exercise testing may be indicated in patients with mitral valve disease who have no other apparent cause of dyspnea on exertion, to rule out the presence of dynamic MR.</p>
          <p>SE provides important objective data and can be performed in conjunction with cardiopulmonary exercise testing by adding other functional assessment variables, such as oxygen consumption.</p>
          <p>In patients with primary MR, the main parameters that can be analyzed during SE are worsening of MR on exertion (increase in ERO &gt; 10 mm), right ventricular dysfunction, and increase in PASP &gt; 60 mm Hg<sup><xref ref-type="bibr" rid="B125">125</xref>,<xref ref-type="bibr" rid="B126">126</xref></sup> (<xref ref-type="table" rid="t47">Table 11.1</xref>), which are predictors of worse prognosis. The onset of symptoms or a drop in systolic blood pressure are also indicative of worse prognosis.</p>
          <p>In a study by Kusunose et al., the presence of tricuspid annular plane systolic excursion (TAPSE) &lt; 1.9 cm or PASP &gt; 57 mm Hg during exertion were predictors of progression to mitral valve surgery in asymptomatic patients with severe MR.<sup><xref ref-type="bibr" rid="B127">127</xref></sup> The absence of myocardial reserve, as indicated by an increase in ejection fraction &#8804; 5% or an absolute increase in LV global longitudinal strain &#8804; 2%, has also been shown to be associated with a worse prognosis in MR patients undergoing SE.<sup><xref ref-type="bibr" rid="B128">128</xref>,<xref ref-type="bibr" rid="B129">129</xref></sup></p>
          <p>SE can be used to evaluate patients with secondary MR, especially when an ischemic component is suspected as the underlying functional mechanism. In patients with nonischemic dilated cardiomyopathy (NIDCM), improvement in MR severity resulting from mobilization of contractile reserve is common and portends a good prognosis, while in patients with ischemic cardiomyopathy, there may be worsening of MR severity, indicating a worse prognosis<sup><xref ref-type="bibr" rid="B130">130</xref>,<xref ref-type="bibr" rid="B131">131</xref></sup> and suggesting that the mitral valve must be repaired during coronary artery bypass graft surgery.</p>
          <p>The suggested examination protocol for stress echocardiography in MVD is shown below.</p>
        </sec>
        <sec>
          <title>11.3. Stress Echocardiography Protocol for Evaluation of Mitral Valve Lesions</title>
          <p>Exercise stress echocardiography is preferred and can be performed on a reclining ergometer (echo couch), stationary bicycle, or treadmill. Exercise is symptom-limited and test cessation should occur upon exceeding the target heart rate or if fatigue or complications arise (arrhythmias, typical chest pain, dizziness, precipitous decline in blood pressure). ECG and noninvasive blood pressure monitoring throughout the procedure are mandatory.</p>
          <p>When using a cycle ergometer, the protocol may start with a 25W load, increasing by 25W every 2&#8211;3 minutes, with the advantage of being able to continuously monitor the echocardiogram and evaluate right ventricular function, parameters for assessing valvular lesions (mean gradients, severity of mitral valve regurgitation), left ventricular function, and PASP. The maximum workload achieved is lower than that obtained on a treadmill, although it is sufficient for the evaluation of valvular heart disease during exercise.</p>
          <p>In the case of treadmill testing, the Bruce or modified Bruce protocols, or ramp protocol, are commonly used under the supervision of a qualified exercise testing provider. Fatigue or any complications should prompt test cessation. Echocardiographic images and data should be acquired at rest and immediately after exertion, taking care not to prolong the post-exercise examination excessively (image capture ideally within 90 seconds of cessation of exertion).</p>
        </sec>
      </sec>
      <sec>
        <title>12. Stress Echocardiography in Aortic Valve Disease</title>
        <sec>
          <title>12.1. Aortic Stenosis</title>
          <p>Aortic valve stenosis is an increasingly prevalent condition in our setting, particularly due to senile valvular degeneration associated with population aging.</p>
          <p>Significant aortic stenosis (AS) is defined by an aortic valve area (AVA) of &#8804; 1.0 cm<sup>2</sup>. Normally, the pressure gradient across the valve correlates with the transvalvular flow and the valve orifice.<sup><xref ref-type="bibr" rid="B132">132</xref></sup></p>
          <p>A complete assessment of the aortic valve requires evaluation of the transaortic gradient and flow, as well as of the AVA at rest and under stress, especially when transvalvular flow is reduced. If the AVA is &lt; 1 cm<sup>2</sup> with a high transvalvular gradient at rest (mean gradient &gt; 40 mm Hg) and the peak aortic valve velocity is &gt; 4.0 m/s, a diagnosis of significant aortic stenosis can already be established.<sup><xref ref-type="bibr" rid="B114">114</xref></sup></p>
          <p>Among the four categories of AS &#8211; high-gradient, classic low flow-low gradient (LFLG), paradoxical LFLG, and normal flow-low gradient &#8211; stress echocardiography is most important in the classic LFLG form, i.e., with a reduced ejection fraction. A low resting gradient in the presence of a reduced AVA does not rule out severe AS, which can occur due to a reduced ejection fraction, but low-flow AS with preserved ejection fraction (paradoxical) can also occur.</p>
          <p><underline>Indication</underline>: SE is definitively indicated in AS when the ejection fraction is reduced (i.e., AVA &#8804; 1.0 cm<sup>2</sup>, LVEF &lt; 50%, and mean transaortic gradient &lt; 40 mm Hg). In these cases, it becomes important to differentiate truly severe fixed aortic valve stenosis from pseudo-severe aortic stenosis, in which the primary problem is cardiomyopathy, leading to overestimation of the severity of the aortic valve lesion due to inadequate valve opening secondary to myocardial impairment.<sup><xref ref-type="bibr" rid="B133">133</xref>-<xref ref-type="bibr" rid="B135">135</xref></sup> The dobutamine stress protocol used in these cases is demonstrated in <xref ref-type="fig" rid="f53">Figure 12.1</xref>.</p>
          <fig id="f53">
            <label>Figure 12.1</label>
            <caption>
              <title>Low-dose dobutamine protocol used in classic low-flow, low-gradient aortic stenosis.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <p>In classic LFLG AS, low-dose DSE is indicated to assess for the presence of contractile/flow reserve, which, if present, allows assessment of the severity of AS. Three response patterns may be seen<sup><xref ref-type="bibr" rid="B133">133</xref></sup> (<xref ref-type="fig" rid="f54">Figure 12.2</xref>):</p>
          <list list-type="order">
            <list-item>
              <p>Increased flow reserve &#8805; 20% with a clear increase in AVA to &gt; 1.0 cm<sup>2</sup> and a slight increase in the transvalvular gradient, indicating pseudo-severe AS; optimized medical management should be recommended.</p>
            </list-item>
            <list-item>
              <p>Increased flow reserve &#8805; 20% with no change in AVA (remains &#8804; 1.0 cm<sup>2</sup>) and a increase in the transvalvular gradient (generally to a mean gradient of &gt;40 mm Hg), indicating true-severe, fixed aortic stenosis; aortic valve replacement is recommended.</p>
            </list-item>
            <list-item>
              <p>When there is no adequate increase in flow reserve (stroke volume increases by less than 20%), and the other parameters therefore remain essentially unchanged, the test is compromised and the severity of AS is considered indeterminate. In these cases, a computed tomography scan with calculation of the aortic valve calcium score helps estimate AS severity. This scenario occurs in one-third of patients and is associated with worse prognosis. Nevertheless, this response pattern should not contraindicate surgery, since many such patients experience improved cardiac performance after aortic valve replacement.</p>
            </list-item>
          </list>
          <fig id="f54">
            <label>Figure 12.2</label>
            <caption>
              <title>Indications for dobutamine stress echocardiography in classic low-flow, low-gradient aortic stenosis and possible responses to the test according to the presence or absence of flow reserve. AS: aortic stenosis; Dob: dobutamine; LVEF: left ventricular ejection fraction; AVA: aortic valve area; SVI: stroke volume index; MG: mean gradient.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <p>Clavel et al.<sup><xref ref-type="bibr" rid="B136">136</xref></sup> suggest that, when the stroke volume is &lt;20% during DSE, the projected AVA should be calculated considering an estimated normal transvalvular flow (i.e., flow = stroke volume/ejection fraction), and the projected valve area at a normal flow rate, which is standardized as 250 mL/s, can be calculated using the following formula: projected AVA = resting AVA + (change in AVA/change in flow) &#215; (250 &#8211; flow rate), where a projected AVA &#8804;1.0 cm<sup>2</sup> is indicative of severe AS.<sup><xref ref-type="bibr" rid="B136">136</xref>-<xref ref-type="bibr" rid="B138">138</xref></sup> A &gt; 20-bpm increase in HR during DSE or the development of arrhythmias or hypotension should prompt test cessation.</p>
          <p>For patients with paradoxical LFLG AS, with EF &#8805; 50%, AVA &#8804; 1.0 cm<sup>2</sup>, mean gradient &lt; 40 mm Hg, and indexed stroke volume &#8804; 35 mL/m<sup>2</sup>, DSE is not officially recommended due to limited scientific evidence and the possibility of significant hypotension due to the risk of a dynamic gradient in the left ventricular outflow tract. A Computed tomography calcium scoring showing values &#8805; 2000 Agatston units in men and &#8805; 1200 in women suggests the possibility of significant AS. In addition, values &#8805; 3000 in men and &#8805; 1600 in women confirm significant AS.<sup><xref ref-type="bibr" rid="B137">137</xref></sup></p>
          <p>For asymptomatic patients with severe high-gradient AS, exercise stress echocardiography, preferably done on a reclining ergometer or echo couch, is considered to add prognostic value beyond that of exercise stress test alone.<sup><xref ref-type="bibr" rid="B99">99</xref></sup> The finding of an increase in mean transvalvular gradient &gt; 20 mm Hg during exercise reflects lower valvular compliance and greater lesion severity.<sup><xref ref-type="bibr" rid="B99">99</xref>,<xref ref-type="bibr" rid="B139">139</xref></sup> These patients have a higher risk of cardiovascular events. Other findings that SE may demonstrate include an increase in PASP &gt; 60 mm Hg. However, there is still no robust data to support a routine indication for ESE in these patients<sup><xref ref-type="bibr" rid="B110">110</xref></sup> (<xref ref-type="fig" rid="f55">Figure 12.3</xref>).</p>
          <fig id="f55">
            <label>Figure 12.3</label>
            <caption>
              <title>Different stress echocardiography modalities and parameters of interest according to the type of aortic valve lesion. DSE: dobutamine stress echo; AR: aortic regurgitation; AS: aortic stenosis; AVA: aortic valve area; Ex: exercise; Ex-MG: mean gradient during exercise; LVEDD: left ventricular end-diastolic diameter; LVEF: left ventricular ejection fraction; LVESD=left ventricular end-systolic diameter, LVESI=left ventricular end-systolic index, PAP=pulmonary artery systolic pressure.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
        </sec>
        <sec>
          <title>12.2. Aortic Insufficiency</title>
          <p>In severe, chronic aortic insufficiency (or aortic regurgitation), patients may be asymptomatic and still progress to latent or overt ventricular dysfunction, which may be irreversible.</p>
          <p>In these cases, ESE or DSE is able to identify the presence or absence of a contractile reserve (increase in ejection fraction by at least 5% or absolute longitudinal strain &#8805; 2%) or flow reserve (increase in stroke volume &#8805; 20%) before surgical intervention, factors which predict functional recovery after aortic valve replacement.<sup><xref ref-type="bibr" rid="B110">110</xref>,<xref ref-type="bibr" rid="B140">140</xref></sup></p>
          <p>Validation of SE to predict outcomes in this subgroup of asymptomatic patients with severe aortic insufficiency is limited, mainly due to the small number of available studies.<sup><xref ref-type="bibr" rid="B114">114</xref>,<xref ref-type="bibr" rid="B141">141</xref></sup></p>
        </sec>
      </sec>
      <sec>
        <title>13. Stress Echocardiography in Dilated Cardiomyopathy</title>
        <p>Dilated cardiomyopathy (DCM) is a primary heart disease characterized by myocardial enlargement in the absence of other previously known etiologies, as well as systolic dysfunction. As the number of diagnosed cases grows, assessing patients&#8217; current status and prognosis is becoming increasingly important, given that advances in treatment have enabled increased survival rates.</p>
        <p>SE has proven to be of great importance in this population for etiological diagnosis and prognostic stratification through analysis of contractile reserve; assessment of functional status under induced stress conditions; determination of who will benefit from beta blocker therapy; and identification of patients with a worse prognosis in terms of cardiac death and need for transplantation.</p>
        <p>Although there is no established consensus on the optimal protocol, high-dose dobutamine (up to 40 mcg/kg/min) without addition of atropine is most common, mainly because it elicits a more complete contractile response and allows for the assessment of inotropic reserve in these patients who are often on beta blockers, reducing the risk of false negative results without adding to the risk of major complications.<sup><xref ref-type="bibr" rid="B99">99</xref></sup> It has been suggested that an increase in contractility, expressed by the change in the WMSI at peak dobutamine stress and baseline values, and an increase &#8805; 5% in LVEF during dobutamine infusion are associated with better survival rates, lower rates of hospitalization for heart failure, and an increase in LVEF during follow-up. Patients with a contractile reserve respond better to beta blocker therapy, are less likely to require transplantation, and show an inverse relationship to the extent of interstitial fibrosis.<sup><xref ref-type="bibr" rid="B99">99</xref>,<xref ref-type="bibr" rid="B142">142</xref>-<xref ref-type="bibr" rid="B146">146</xref></sup> Conversely, the absence of contractile reserve in patients with preserved or reduced LVEF is frequently associated with limited coronary flow reserve, and is therefore a marker of latent left ventricular systolic dysfunction and subclinical cardiomyopathy.<sup><xref ref-type="bibr" rid="B99">99</xref></sup></p>
        <p>The most common adverse event associated with high-dose dobutamine in this population was complex ventricular arrhythmia (multifocal premature ventricular contractions in 6.4% and nonsustained ventricular tachycardia in 1.6%), generally occurring in patients with hypokalemia.<sup><xref ref-type="bibr" rid="B142">142</xref>,<xref ref-type="bibr" rid="B143">143</xref></sup></p>
        <p>The vasodilator-based protocol (dipyridamole 0.84 mg/kg over 10 min, with the addition of handgrip exercise at the peak of infusion to increase test sensitivity) is rarely used to assess contractile reserve; however, it has been proposed as an alternative to dobutamine, as it is less arrhythmogenic, better tolerated, and provides prognostic information similar to that in patients with ischemic heart disease, in addition to not being influenced by beta blockade;<sup><xref ref-type="bibr" rid="B147">147</xref></sup> however, it has not gained much traction in clinical practice for this indication when compared to dobutamine.<sup><xref ref-type="bibr" rid="B49">49</xref>,<xref ref-type="bibr" rid="B148">148</xref>-<xref ref-type="bibr" rid="B150">150</xref></sup></p>
        <p>The following tables provide recommendations for stress echocardiography in DCM (<xref ref-type="table" rid="t48">Tables 13.1</xref>, <xref ref-type="table" rid="t49">13.2</xref>, <xref ref-type="table" rid="t50">13.3</xref>, <xref ref-type="table" rid="t51">13.4</xref> and <xref ref-type="table" rid="t52">13.5</xref>).</p>
        <table-wrap id="t48">
          <label>Table 13.1</label>
          <caption>
            <title>Parameters to be assessed in stress echocardiography for dilated cardiomyopathy</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="50%">
              <col/>
              <col/>
            </colgroup>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr style="background-color:#76B4CF">
                <td align="left" valign="middle" colspan="2">
                  <bold>1. What should be assessed during stress echocardiography of the patient with dilated cardiomyopathy?</bold>
                </td>
              </tr>
              <tr>
                <td align="left" valign="middle">- Contractile reserv</td>
                <td align="left" valign="middle">- Diastolic reserve</td>
              </tr>
              <tr>
                <td align="left" valign="middle">- Stress-induced ischemia</td>
                <td align="left" valign="middle">- Dynamic mitral regurgitation</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">- Change in PASP</td>
                <td align="left" valign="middle">- Pulmonary congestion (B-lines)</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <table-wrap id="t49">
          <label>Table 13.2</label>
          <caption>
            <title>Parameters to be measured in stress echocardiography for dilated cardiomyopathy</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="100%">
              <col/>
            </colgroup>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr style="background-color:#76B4CF">
                <td align="left" valign="middle">
                  <bold>2. What should be measured?</bold>
                </td>
              </tr>
              <tr>
                <td align="left" valign="middle">- E and A waves</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">- e' (PW Doppler)</td>
              </tr>
              <tr>
                <td align="left" valign="middle">- Mitral and tricuspid regurgitation (CW Doppler)</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <table-wrap id="t50">
          <label>Table 13.3</label>
          <caption>
            <title>Time points for measurement of parameters in stress echocardiography for dilated cardiomyopathy</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="100%">
              <col/>
            </colgroup>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr style="background-color:#76B4CF">
                <td align="left" valign="middle">
                  <bold>3. When to measure (dobutamine protocol)?</bold>
                </td>
              </tr>
              <tr>
                <td align="left" valign="middle">- Baseline - Low dose - Peak infusion</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <table-wrap id="t51">
          <label>Table 13.4</label>
          <caption>
            <title>Expected responses to stress echocardiography in dilated cardiomyopathy</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="100%">
              <col/>
            </colgroup>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr style="background-color:#76B4CF">
                <td align="left" valign="middle">
                  <bold>4. Expected responses:</bold>
                </td>
              </tr>
              <tr>
                <td align="left" valign="middle">- Increase or no increase in left ventricular contractility</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">- Reduction or increase in mitral regurgitation</td>
              </tr>
              <tr>
                <td align="left" valign="middle">- Changes in PASP and E/e' ratio</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">- Presence or absence of B-lines in the lung fields</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <table-wrap id="t52">
          <label>Table 13.5</label>
          <caption>
            <title>Protocols used for stress echocardiography in dilated cardiomyopathy (A: dobutamine; B: dipyridamole)</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="100%">
              <col/>
            </colgroup>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr style="background-color:#76B4CF">
                <td align="left" valign="middle"><bold>5. Protocols</bold> (<xref ref-type="fig" rid="f56">Figure 12.4</xref>).</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <fig id="f56">
          <label>Figure 12.4</label>
          <caption>
            <title>Protocols used for stress echocardiography in dilated cardiomyopathy (A: dobutamine; B: dipyridamole).</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
      </sec>
      <sec>
        <title>14. Stress Echocardiography in Chagas Cardiomyopathy</title>
        <p>Patients with chronic Chagas disease cardiomyopathy (CCDC) frequently present with atypical chest pain and ECG abnormalities, such as ST segment changes and pathological Q waves, along with regional wall motion abnormalities and perfusion disorders that mimic the presentation of atherosclerotic coronary artery disease.<sup><xref ref-type="bibr" rid="B151">151</xref></sup></p>
        <p>As recently as a few decades ago, patients with Chagas disease were predominantly rural workers with a low risk profile for obstructive coronary artery disease. With the growing urbanization of this population from 1980 onwards, they became exposed to the same risk factors for atherosclerotic disease as individuals not infected with <italic>Trypanosoma cruzi</italic>.<sup><xref ref-type="bibr" rid="B152">152</xref></sup> However, in most cases, examination of the epicardial coronary arteries reveals absence of significant subepicardial atherosclerotic obstruction, with any changes being attributed to coronary microvascular dysfunction.<sup><xref ref-type="bibr" rid="B153">153</xref></sup></p>
        <p>Some studies have evaluated the applicability of stress echocardiography in Chagas disease. Microvascular ischemia is considered an early disorder in the natural history of the disease, preceding regional ventricular dysfunction and possibly related to induction of myocardial hibernation or stunning. Results obtained from a stress echocardiography study using dipyridamole demonstrated a reduction in coronary vasodilator reserve, an index of microvascular dysfunction, in patients with the indeterminate form of the disease when compared to normal controls.<sup><xref ref-type="bibr" rid="B154">154</xref></sup></p>
        <p>Regarding chronotropic response, dobutamine echocardiography demonstrated that patients with Chagas disease exhibited blunted inotropic and chronotropic responses when compared to a control group. Furthermore, pharmacological stress echocardiography can demonstrate the presence of a biphasic contractile response in these patients, despite the absence of epicardial coronary artery disease.<sup><xref ref-type="bibr" rid="B155">155</xref></sup></p>
        <p>Regarding predictive value for progression of heart disease, the presence of complex ventricular arrhythmias on stress echocardiography was an independent predictor of disease progression in a group of patients in the early stages of Chagas cardiomyopathy.<sup><xref ref-type="bibr" rid="B156">156</xref></sup></p>
        <p>Finally, regarding the use of dobutamine in arrhythmogenic heart disease, pharmacological stress echocardiography proved safe in a cohort of patients with Chagas cardiomyopathy under investigation for coronary artery disease. The presence of an abnormal regional wall motion index at rest was an independent predictor for the development of complex arrhythmias during the examination.<sup><xref ref-type="bibr" rid="B157">157</xref></sup></p>
      </sec>
      <sec>
        <title>15. Stress Echocardiography in Hypertrophic Cardiomyopathy</title>
        <p>HCM is a common heart disease of genetic origin, with an autosomal dominant inheritance pattern and equal distribution by sex. Prevalence varies depending on age, subclinical or clinical status, and ethnicity.<sup><xref ref-type="bibr" rid="B158">158</xref></sup> Clinical suspicion may be aroused by manifestation of symptoms, detection of a heart murmur, an abnormal ECG pattern, or a cardiac event. In addition, it may be an incidental finding during echocardiography performed for other indications.<sup><xref ref-type="bibr" rid="B159">159</xref></sup></p>
        <p>Echocardiography plays a very important role in confirming the diagnosis, determining the pattern of hypertrophy, evaluating LVOTO, systolic anterior motion (SAM) of the mitral valve, and mitral regurgitation (MR), as well as assessing left ventricular systolic and diastolic function, left atrial volume, and pulmonary pressure.<sup><xref ref-type="bibr" rid="B160">160</xref></sup></p>
        <p>SE has been widely used in this setting, primarily to measure dynamic and inducible LVOTO in symptomatic patients with a resting peak LVOT gradient &lt; 50 mm Hg, to detect MR, and to monitor treatment response. The importance of a gradient &gt; 50 mm Hg, whether at rest or post-exercise, lies in the fact that it is the conventional limit for invasive intervention when symptoms are not controlled with pharmacotherapy.<sup><xref ref-type="bibr" rid="B158">158</xref></sup> ESE is the most recommended modality in these cases.</p>
        <p>Exercise can be performed on a reclining ergometer/echo couch, stationary bicycle, or treadmill. The treadmill has been suggested to induce a higher LVOT gradient. The choice of protocol should take into account the patient's overall condition, the physician's experience, and the resources at the institution's disposal.</p>
        <p>Before the test, it is important to be aware of the patient's condition (functional class, hydration status, timing of last meal, intake of alcoholic beverages, etc.) and pharmacological factors (vasodilators, diuretics), as these can influence the outcome of the examination. Unlike in other stress test modalities, beta blockers should not be withdrawn before exercise in this patient population.</p>
        <p>Ultrasound enhancement agents are useful in confirming septal and apical hypertrophy, detecting apical thrombi, and excluding apical aneurysms.<sup><xref ref-type="bibr" rid="B161">161</xref></sup></p>
        <p>It is essential that the patient be informed of the purpose of the study and its possible outcomes. As one of the goals of SE is to quantify the LVOT gradient in symptomatic patients with no gradient or a low resting gradient, it is recommended that the gradient be measured as frequently as possible throughout the examination. SAM, MR, left ventricular wall motion abnormalities, and diastolic dysfunction should also be assessed.</p>
        <p>The ECG should be monitored continuously for any change. Clinical and echocardiographic parameters are evaluated during exercise and in the early and late recovery phases, while preload decreases gradually. If exercise stress does not cause a significant increase in the LVOT gradient, assessment of the post-exercise gradient in the orthostatic position should be considered. A hypertensive response, any reduction in BP &gt; 10 mm Hg compared to the resting BP before the examination, dyspnea, chest discomfort, and sustained tachyarrhythmia are indications for test cessation.<sup><xref ref-type="bibr" rid="B162">162</xref></sup> LVOTO at a low exercise load correlates with low functional capacity. LVOTO is a risk factor for sudden death and major cardiovascular events.<sup><xref ref-type="bibr" rid="B163">163</xref></sup></p>
        <p>Since stress echocardiography is an operator-dependent technique, a supervised learning curve is essential for the echocardiographer to gain expertise in patients with HCM, in order to obtain reliable and reproducible results that allow for informed decisions to support patient management and follow-up. Notably, the clinical course of HCM is heterogeneous and unpredictable. SE has the potential to differentiate non-obstructive HCM from HCM with a dynamic gradient and, taken together with exercise capacity, blood pressure, and heart rate response, predict the future development of heart failure, thus informing the choice of management strategies available to each patient in the context of this complex genetic disease. Procedures such as surgical septal myectomy and percutaneous alcohol septal ablation have Class I indications for symptomatic patients with a resting LVOT gradient and those without an acceptable response to pharmacological therapy.<sup><xref ref-type="bibr" rid="B164">164</xref></sup></p>
      </sec>
      <sec>
        <title>16. Stress Echocardiography in the Evaluation of Right Ventricular Function and Pulmonary Hypertension</title>
        <p>Pulmonary hypertension (PAH) is a pathophysiological derangement that can involve a wide range of clinical conditions and be associated with countless respiratory and/or cardiovascular diseases. Regardless of the underlying disease process and the site of functional changes, PAH is defined by a mean resting pulmonary artery pressure (mPAP) of &gt;20 mm Hg as measured by right heart catheterization (RHC).<sup><xref ref-type="bibr" rid="B165">165</xref></sup></p>
        <p>Recently, there has been increasing interest in the application of SE for the detection and assessment of the severity of PAH and right heart dysfunction.<sup><xref ref-type="bibr" rid="B166">166</xref>,<xref ref-type="bibr" rid="B167">167</xref></sup></p>
        <p>RHC is the gold-standard method for evaluating pulmonary hemodynamics. It allows diagnosis and classification of PAH. According to current consensus guidelines, exercise RHC is the recommended method for assessment of cardiopulmonary hemodynamics. However, this method entails some technical challenges, requiring experienced personnel, special equipment, and additional procedure time.<sup><xref ref-type="bibr" rid="B165">165</xref></sup></p>
        <p>SE of the pulmonary circulation and right ventricle reveals relevant prognostic differences between healthy individuals, athletes, high-altitude residents, and patients with various cardiorespiratory conditions. It can assess pulmonary circulation and right ventricular behavior noninvasively in these individuals, and it also aids in the diagnosis of latent or overt PAH, with or without RV dysfunction, adapting to increased workload.<sup><xref ref-type="bibr" rid="B168">168</xref></sup></p>
        <p>Similar to the concept of exercise RHC, supplementing standard echocardiography with a stress test can improve diagnostic accuracy in detecting postcapillary pulmonary hypertension. Furthermore, exercise stress has added value in the management of patients with PAH, as it also allows assessment of complex RV mechanics (e.g., contractile reserve) and the ability of the pulmonary vasculature to accommodate increased flow.<sup><xref ref-type="bibr" rid="B168">168</xref></sup></p>
        <p>The echocardiographic measures of RV function that are independent predictors of mortality in PAH include a TAPSE &lt; 18 mm,<sup><xref ref-type="bibr" rid="B169">169</xref>-<xref ref-type="bibr" rid="B173">173</xref></sup> RV fractional area change (FAC) &lt; 35%, a peak tricuspid annular systolic velocity (S&#8217;) &lt; 9.7 cm/s,<sup><xref ref-type="bibr" rid="B174">174</xref></sup> and a Tei index &gt; 0.40 by pulsed Doppler or &gt; 0.55 by tissue Doppler.<sup><xref ref-type="bibr" rid="B175">175</xref></sup></p>
        <p>All the metrics described above can be evaluated at rest and after peak stress (exercise or dobutamine stress echocardiography). To date, most data have been derived from healthy volunteers, but several small and medium-sized studies have evaluated the prognostic role of right ventricular contractile reserve in patients with PAH, valvular heart disease, and heart failure.<sup><xref ref-type="bibr" rid="B176">176</xref></sup></p>
        <p>Whether non-invasive echocardiographic assessment is equally reliable and generally feasible for defining disease conditions with or at risk of PAH is still unknown. Similar limitations apply to the echocardiographic assessment of RV function during exercise.<sup><xref ref-type="bibr" rid="B167">167</xref>,<xref ref-type="bibr" rid="B176">176</xref></sup></p>
        <p>One potential noninvasive measure of RV contractile reserve using exercise stress was proposed by Gr&#252;nig et al., who demonstrated that an exercise-induced increase in pulmonary artery pressure (PAP) was a measure of RV contractile reserve and an independent prognostic factor in patients with precapillary pulmonary hypertension.<sup><xref ref-type="bibr" rid="B177">177</xref></sup></p>
      </sec>
      <sec>
        <title>17. Stress Echocardiography in Post-COVID-19 Assessment</title>
        <p>Most publications regarding the cardiovascular manifestations of COVID-19 have evaluated the acute phase of infection, demonstrating that the presence of cardiac dysfunction detected by resting echocardiography was associated with a worse prognosis in patients with severe COVID-19.<sup><xref ref-type="bibr" rid="B178">178</xref></sup> Due to the high risk of cross-contamination via droplet transmission, exercise stress echocardiography was largely postponed or canceled during the pandemic.<sup><xref ref-type="bibr" rid="B179">179</xref>,<xref ref-type="bibr" rid="B180">180</xref></sup> In low-risk COVID-19 patients where the indication was appropriate and postponement was not possible, pharmacological stress echocardiography was the preferred option.<sup><xref ref-type="bibr" rid="B179">179</xref>,<xref ref-type="bibr" rid="B180">180</xref></sup></p>
        <p>After the end of the pandemic state of emergency, several studies attempted to describe the long-term consequences of COVID-19 on the cardiovascular system, but most still only used resting echocardiography. Subsequently, very few publications explored the use of stress echocardiography as a tool in the assessment of patients after recovery from SARS-CoV-2 infection. A prospective study of 174 young athletes with normal ventricular function at rest after COVID-19 aimed to identify myocardial involvement through a comprehensive functional protocol that included physical stress echocardiography.<sup><xref ref-type="bibr" rid="B181">181</xref></sup> Signs of myocardial involvement were found in five athletes (2.9%), three of whom showed clinically significant changes on exertion, including ventricular arrhythmia in two and regional wall motion abnormalities in one subject.<sup><xref ref-type="bibr" rid="B181">181</xref></sup> Although rare, myocardial involvement was only detected during exertion, suggesting that screening with exercise stress echocardiography may be useful in selected cases for guidance on returning to competitive athletic activity after SARS-CoV-2 infection. Another study evaluated 71 patients recovering from COVID-19, most of whom were symptomatic, using a protocol that combined physical stress echocardiography and cardiopulmonary exercise testing.<sup><xref ref-type="bibr" rid="B182">182</xref></sup> Peak oxygen consumption (VO<sub>2</sub>) was lower in post-COVID-19 patients compared to the control group, due to a combination of chronotropic incompetence and blunted left ventricular stroke volume reserve (insufficient increase in stroke volume during exertion).<sup><xref ref-type="bibr" rid="B182">182</xref></sup> These studies highlight the importance of assessing cardiac function not only at rest but also under stress, such as exercise, to fully understand the impact of COVID-19 infection on the heart. Ongoing investigations may, through the use of stress echocardiography, provide a better understanding of the relationship between a history of SARS-CoV-2 infection, its cardiovascular implications, and physical activity.<sup><xref ref-type="bibr" rid="B183">183</xref></sup></p>
        <p>The use of ultrasound enhancing agents (UEAs) warrants special mention, as these agents are indispensable tools for modern stress echocardiography practice. After December 2020, coinciding with the start of COVID-19 vaccination in the U.S. population, an increase in serious adverse reactions to UEAs containing polyethylene glycol (PEG), such as Sonovue or Lumason (Bracco Diagnostics) and Definity (Lantheus Medical Imaging), was observed. The possibility of cross-reactivity between these UEAs and mRNA-based COVID-19 vaccines (Pfizer/BioNTech and Moderna) was considered as a possible cause, since both contain PEG.<sup><xref ref-type="bibr" rid="B184">184</xref></sup> A retrospective case-control study suggested that individuals with severe adverse reactions to Lumason occurring since March 2021 in the U.S. were more likely to have been vaccinated against COVID-19 than those who did not experience such adverse reactions.<sup><xref ref-type="bibr" rid="B185">185</xref></sup></p>
      </sec>
      <sec>
        <title>18. Stress Echocardiography and Coronary Flow Reserve in Native Vessels</title>
        <p>Coronary flow reserve (CFR) can be assessed through direct analysis of arterial flow during SE. Specific presets allow visualization, without the use of microbubbles, of the left anterior descending (LAD) coronary artery during pharmacological stress with adenosine, dipyridamole, or even dobutamine in at least 90% of cases; the success rate is lower in the posterior descending (PDA) and circumflex (Cx) arteries, particularly in ESE.<sup><xref ref-type="bibr" rid="B23">23</xref>,<xref ref-type="bibr" rid="B186">186</xref>-<xref ref-type="bibr" rid="B189">189</xref></sup></p>
        <p>The CFR is calculated by dividing the diastolic velocity obtained at hyperemia by the diastolic velocity recorded at rest (<xref ref-type="fig" rid="f57">Figure 18.1</xref>). Testing for correlation between the CFR measured during SE and the percentage of coronary stenosis found that a CFR &#8805; 2 indicates normality and is consistent with a good prognosis. The CFR may be reduced (&lt;2) by coronary stenosis and/or a compromised microcirculation, and is an independent predictor of adverse outcomes. Lower CFR values are more indicative of significant coronary stenosis (<xref ref-type="table" rid="t53">Table 18.1</xref>).<sup><xref ref-type="bibr" rid="B187">187</xref>,<xref ref-type="bibr" rid="B190">190</xref>-<xref ref-type="bibr" rid="B194">194</xref></sup></p>
        <fig id="f57">
          <label>Figure 18.1</label>
          <caption>
            <title>Normal baseline CFR in the left anterior descending artery, increasing significantly (CFR = 3.3) with 30 mcg/kg/min dobutamine. LAD: left anterior descending artery; DSE: dobutamine stress echocardiography; HR: heart rate; DPV: diastolic peak velocity; CFR (coronary flow reserve) = DPV during stress / DPV at baseline. Normal CFR (&#8805; 2) and early CFR (before reaching the target heart rate of the test), recorded during intermediate stages of DSE.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>In intermediate LAD stenosis (50&#8211;70%), percutaneous coronary intervention can be indicated when the CFR is reduced versus medical management when the CFR is normal, as there was no difference in the rate of death, myocardial infarction, unstable angina, or myocardial revascularization between the two groups.<sup><xref ref-type="bibr" rid="B195">195</xref></sup></p>
        <p>An abnormal CFR has high sensitivity and specificity for diagnosing restenosis in the three main coronary arteries (<xref ref-type="table" rid="t53">Table 18.1</xref>). One study showed high feasibility of recording in the ADA (95%), PDA (85%), and Cx (81%), with a UEA or microbubble contrast used in 22% of cases.<sup><xref ref-type="bibr" rid="B194">194</xref></sup></p>
        <table-wrap id="t53">
          <label>Table 18.1</label>
          <caption>
            <title>Correlation between coronary flow reserve and percent coronary stenosis</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="13%">
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr style="background-color:#76B4CF">
                <th align="left" valign="middle">Authors</th>
                <th align="center" valign="middle">No. of cases</th>
                <th align="center" valign="middle">CFR (cutoff)</th>
                <th align="center" valign="middle">Stressor</th>
                <th align="center" valign="middle">% Stenosis</th>
                <th align="center" valign="middle">Sensitivity</th>
                <th align="center" valign="middle">Specificity</th>
                <th align="center" valign="middle">Accuracy</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle">Nohotomi et al.<sup><xref ref-type="bibr" rid="B187">187</xref></sup></td>
                <td align="center" valign="middle">110 LAD</td>
                <td align="center" valign="middle">&lt; 2</td>
                <td align="center" valign="middle">Dipyridamole</td>
                <td align="center" valign="middle">&gt; 50%</td>
                <td align="center" valign="middle">94%</td>
                <td align="center" valign="middle">65%</td>
                <td align="center" valign="middle">81%</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle" rowspan="3">Voci et al.<sup><xref ref-type="bibr" rid="B190">190</xref></sup></td>
                <td align="center" valign="middle">44 (LAD+PDA)</td>
                <td align="center" valign="middle">&lt; 2</td>
                <td align="center" valign="middle">Adenosine</td>
                <td align="center" valign="middle">&#8805; 70%</td>
                <td align="center" valign="middle">89%</td>
                <td align="center" valign="middle">96%</td>
                <td align="center" valign="middle">93%</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">18 PDA</td>
                <td align="center" valign="middle">1.4 &#177; 0.54</td>
                <td align="center" valign="middle"/>
                <td align="center" valign="middle">&#8805; 70%</td>
                <td align="center" valign="middle">89%</td>
                <td align="center" valign="middle">91%</td>
                <td align="center" valign="middle">93%</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">19 LAD</td>
                <td align="center" valign="middle">1.12 &#177; 0.49</td>
                <td align="center" valign="middle"/>
                <td align="center" valign="middle">&#8805; 70%</td>
                <td align="center" valign="middle">89%</td>
                <td align="center" valign="middle">100%</td>
                <td align="center" valign="middle">95%</td>
              </tr>
              <tr>
                <td align="left" valign="middle">Lowenstein et al.<sup><xref ref-type="bibr" rid="B191">191</xref></sup></td>
                <td align="center" valign="middle">132 LAD</td>
                <td align="center" valign="middle">&lt; 2</td>
                <td align="center" valign="middle">Dipyridamole</td>
                <td align="center" valign="middle">&gt; 70%</td>
                <td align="center" valign="middle">87%</td>
                <td align="center" valign="middle">73%</td>
                <td align="center" valign="middle">80%</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle" rowspan="2">Matsumara et al.<sup><xref ref-type="bibr" rid="B192">192</xref></sup></td>
                <td align="center" valign="middle">138 LAD</td>
                <td align="center" valign="middle">-</td>
                <td align="center" valign="middle">Adenosine</td>
                <td align="center" valign="middle"/>
                <td align="center" valign="middle"/>
                <td align="center" valign="middle"/>
                <td align="center" valign="middle" rowspan="2"/>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">30 LAD</td>
                <td align="center" valign="middle">&lt; 2</td>
                <td align="center" valign="middle"/>
                <td align="center" valign="middle">&#8805; 70%</td>
                <td align="center" valign="middle">90%</td>
                <td align="center" valign="middle">93%</td>
              </tr>
              <tr>
                <td align="left" valign="middle">Soylu et al.<sup><xref ref-type="bibr" rid="B193">193</xref></sup></td>
                <td align="center" valign="middle">44 LAD</td>
                <td align="center" valign="middle">&lt; 1.6</td>
                <td align="center" valign="middle">Dipyridamole</td>
                <td align="center" valign="middle">&#8805; 55%</td>
                <td align="center" valign="middle">100%</td>
                <td align="center" valign="middle">94%</td>
                <td align="center" valign="middle"/>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle" rowspan="4">Hyodo et al.<sup><xref ref-type="bibr" rid="B194">194</xref></sup></td>
                <td align="center" valign="middle">175 vessels</td>
                <td align="center" valign="middle">-</td>
                <td align="center" valign="middle">Adenosine</td>
                <td align="center" valign="middle">&gt; 50%</td>
                <td align="center" valign="middle"/>
                <td align="center" valign="middle"/>
                <td align="center" valign="middle" rowspan="4"/>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">166 LAD</td>
                <td align="center" valign="middle">&lt; 2</td>
                <td align="center" valign="middle"/>
                <td align="center" valign="middle">&gt; 50%</td>
                <td align="center" valign="middle">86%</td>
                <td align="center" valign="middle">91%</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">149 PDA</td>
                <td align="center" valign="middle">&lt; 2</td>
                <td align="center" valign="middle"/>
                <td align="center" valign="middle">&gt; 50%</td>
                <td align="center" valign="middle">92%</td>
                <td align="center" valign="middle">92%</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">142 CX</td>
                <td align="center" valign="middle">&lt; 2</td>
                <td align="center" valign="middle"/>
                <td align="center" valign="middle">&gt; 50%</td>
                <td align="center" valign="middle">91%</td>
                <td align="center" valign="middle">92%</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN21">
              <p>CFR: Coronary flow reserve; LAD: Left anterior descending artery; PDA: Posterior descending artery; CX: Circumflex artery.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Dobutamine is the most commonly used stressor for pharmacological SE and also has a vasodilatory effect.<sup><xref ref-type="bibr" rid="B196">196</xref></sup> The first study to assess CFR in the LAD under dobutamine stress showed 90% viability. Cases with ischemia (as determined by regional wall motion abnormalities) had a mean CFR of 1.51 &#177; 0.51, while those without ischemia had a mean CFR of 2.76 &#177; 0.65.<sup><xref ref-type="bibr" rid="B186">186</xref></sup></p>
        <p>During dobutamine stress echocardiography, a normal CFR can be attained early, i.e., before the target heart rate for the test is reached.<sup><xref ref-type="bibr" rid="B197">197</xref></sup> Cases reaching a normal CFR before the heart rate endpoint of the test showed a better composite outcome than cases in which normal CFR was recorded only after the submaximal heart rate had been exceeded and cases in which the CFR was abnormal. Once an early normal CFR has been reached, CFR determination can be stopped and the SE continued as normal.<sup><xref ref-type="bibr" rid="B179">179</xref></sup></p>
        <p>Among diabetic patients undergoing dipyridamole and dobutamine SE, in cases without ischemia, an abnormal CFR in the LAD was independently predictive of mortality, and this finding was similar for both techniques.<sup><xref ref-type="bibr" rid="B199">199</xref></sup> This was further corroborated in a study evaluating CFR in the LAD and PDA during dipyridamole stress, which found that an abnormal CFR was predictive of worse prognosis (death and myocardial infarction) in patients without ischemia.<sup><xref ref-type="bibr" rid="B189">189</xref></sup></p>
      </sec>
      <sec>
        <title>19. Stress Echocardiography and Coronary Flow Reserve in Grafts</title>
        <p>Anatomical analysis of epicardial vessel lesions by coronary angiography may not be sufficient to assess the impact of coronary lesions, especially in intermediate obstructions (50&#8211;70%) and in patients with multivessel disease,<sup><xref ref-type="bibr" rid="B200">200</xref></sup> partly due to the changes that stenosis causes in the regulation of circulation. Stenosis &gt; 50% of the vessel lumen increases coronary resistance and decreases pressure distal to the obstruction, with a decrease in CFR.<sup><xref ref-type="bibr" rid="B201">201</xref></sup> For this reason, physiological assessment of the coronary circulation, as a determinant of myocardial revascularization, has improved the outcomes of both surgical and percutaneous procedures, as well as the post-procedure prognosis. For this purpose, several diagnostic methods stand out beyond coronary angiography, including stress echocardiography and CFR analysis by transthoracic Doppler imaging.</p>
        <sec>
          <title>19.1. Stress Echocardiography after Myocardial Revascularization</title>
          <p>Just as a regional wall motion score &gt; 1.7 on stress echocardiography performed before revascularization is predictive of increased postoperative complications,<sup><xref ref-type="bibr" rid="B202">202</xref></sup> an abnormal study after revascularization more than doubles the risk of adverse cardiovascular events,<sup><xref ref-type="bibr" rid="B203">203</xref></sup> even in asymptomatic patients. Although vasodilator stress echocardiography is the best option for these cases, low-dose dobutamine stress, while influenced by several factors, has shown good sensitivity (86.4%) in detecting recovery of contractile reserve after revascularization, especially in previously hypokinetic segments.<sup><xref ref-type="bibr" rid="B204">204</xref></sup></p>
        </sec>
        <sec>
          <title>19.2. Coronary Flow Reserve after Myocardial Revascularization</title>
          <p>Fractional flow reserve, assessed during interventional cardiology studies using either a pressure gradient or flow velocity through the obstruction, is an important tool for the functional analysis of obstructive coronary artery disease (Class IA recommendation).<sup><xref ref-type="bibr" rid="B205">205</xref></sup> Following revascularization, transthoracic Doppler coronary flow measurement and CFR analysis with vasodilator stress can be used as a substitute for invasive methods.<sup><xref ref-type="bibr" rid="B206">206</xref></sup> In internal thoracic (mammary) artery grafts, the finding of biphasic flow with diastolic predominance is indicative of graft patency (<xref ref-type="fig" rid="f58">Figure 19.1</xref>). Increased coronary flow velocity distal to the graft site after vasodilator infusion (dipyridamole 0.84 mg/kg over 6 minutes, although the CFR obtained at 4 minutes is already considered satisfactory, or adenosine 0.14 mg/kg/min over 2 minutes) allows determination of CFR. A ratio between flow at peak hyperemia and baseline flow &gt;2 is considered a good response<sup><xref ref-type="bibr" rid="B207">207</xref></sup> (<xref ref-type="fig" rid="f59">Figure 19.2</xref>).</p>
          <fig id="f58">
            <label>Figure 19.1</label>
            <caption>
              <title>A: Detection of internal thoracic artery flow with pulsed Doppler sample volume placement. B: Recording of flow in the internal mammary-to-coronary artery graft, showing biphasic flow with diastolic predominance, indicating that the graft is patent.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <fig id="f59">
            <label>Figure 19.2</label>
            <caption>
              <title>Coronary flow in an internal thoracic artery graft. A: Baseline coronary flow obtained in the anterior descending artery after anastomosis. B: Flow obtained 6 minutes after dipyridamole infusion, showing a coronary flow reserve (CFR) of 2.35. The slope of the diastolic deceleration time waveform correlates with the resistance offered by the vascular bed to the passage of flow during diastole. Vasodilation reduces vascular resistance, resulting in a faster deceleration of blood flow.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <p>In venous grafts, flow within the graft is predominantly systolic, emptying into the coronary artery during diastole (<xref ref-type="fig" rid="f60">Figure 19.3</xref>). The analysis and interpretation of CFR are similar to those in arterial grafts.</p>
          <fig id="f60">
            <label>Figure 19.3</label>
            <caption>
              <title>Coronary flow in a venous graft to the anterior descending artery. A: Flow in the venous graft, with systolic predominance. B: Flow in the artery distal to the graft, biphasic and with diastolic predominance.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <p>Some conditions can decrease the CFR through arterial grafts without necessarily causing stenosis, such as: atheromatosis of the left subclavian artery or of the arterial graft, which can decrease flow to the grafted artery; diffuse atheromatosis of the distal bed of the irrigated artery; increased microvascular resistance secondary to previous myocardial infarction; abnormalities in the coronary microcirculation; and the timing of the examination, considering the gradual remodeling of arterial grafts, with a progressive increase in CFR. For venous grafts, causes of decreased CFR include graft spasm, a rare but serious condition; graft atherosclerosis; and fibrointimal hypoplasia with fibrosis.</p>
        </sec>
      </sec>
      <sec>
        <title>20. Stress Echocardiography in the Assessment of Myocardial Viability</title>
        <p>The clinical approach to akinetic myocardial areas demonstrably viable on imaging (hibernating myocardium) is controversial, mainly after two large trials, STICH (Surgical Treatment for Ischaemic Heart Failure) and HEART (Heart Failure Revascularization), showed that despite improvement in left ventricular ejection fraction there was no positive impact on the long-term prognosis of these patients.<sup><xref ref-type="bibr" rid="B208">208</xref>,<xref ref-type="bibr" rid="B209">209</xref></sup> Hibernating myocardium refers to dysfunctional areas due to chronic hypoperfusion caused by obstructive coronary artery disease, which is possibly reversible after revascularization.<sup><xref ref-type="bibr" rid="B210">210</xref></sup> This has long been an intriguing phenomenon in cardiology, and remains a controversial topic. Among imaging methods, positron emission tomography (PET) has the highest sensitivity and negative predictive value, while dobutamine stress echocardiography is most specific and has the highest positive predictive value per analyzed segment.<sup><xref ref-type="bibr" rid="B211">211</xref></sup> Currently, there is ongoing conceptual reconsideration regarding how revascularization should be guided by prior analysis of myocardial viability and what would the benefit of doing so. The classic concept ascribed greater value to the presence of viability, regardless of coronary anatomy for revascularization. This strategy has been shown to improve ejection fraction, quality of life, symptoms, and ischemic heart failure; however, improvement in the ejection fraction per se did not necessarily translate into an improvement in survival. The current approach aims for a more myocardial-specific functional assessment, improving therapeutic planning towards a more rational and physiological revascularization. Therefore, there is a greater concern in preserving viable ischemic segments where the anatomy is favorable for surgical revascularization, thereby reducing the rate of fatal heart attacks and arrhythmias.<sup><xref ref-type="bibr" rid="B210">210</xref></sup> Interestingly, percutaneous revascularization guided by viability studies has not demonstrated any benefit.<sup><xref ref-type="bibr" rid="B212">212</xref>,<xref ref-type="bibr" rid="B213">213</xref></sup></p>
        <sec>
          <title>20.1. Stress Echo Protocols for Assessment of Myocardial Viability</title>
          <p>Prior to myocardial viability studies, a routine targeted transthoracic echocardiogram is performed. This will allow the examiner to understand the baseline parameters to be analyzed under dynamic conditions, as well as the quality of the echocardiographic window and the need to use ultrasound enhancing agents. Assessment of myocardial viability is performed using the low-dose dobutamine pharmacological stress echocardiogram protocol (starting at 2.5 or 5 mcg/kg/min, with increments to 7.5 and 10 mcg/kg/min every 3 to 5 minutes, up to 20 mcg/kg/min). The protocol can also be performed in patients who are on beta blockers. Although viability is assessed with low-dose of dobutamine, it is worth continuing the examination with higher doses (up to 40 mcg/kg/min, with or without atropine) to evaluate not only viability but also the presence of stress-induced myocardial ischemia, which greatly contributes to optimizing management. This of course applies only to those patients whose condition allows the protocol to progress further, preferably those whose ejection fraction is not greatly reduced due to marked hypokinesis of multiple segments in addition to akinetic areas; in these cases, the risk of the high-dose protocol is greater and the sensitivity of the method for diagnosing ischemia is reduced due to the marked, "balanced" abnormality of all walls of the left ventricle.</p>
          <p>Segments akinetic at rest are deemed viable when they exhibit increased thickness (&#8805; 0.5 cm) and contractility (contractile reserve) during dobutamine stress. A biphasic response as the protocol progresses (improvement at low doses and worsening at higher doses of dobutamine, i.e., 20 mcg/kg/min or more) suggests a greater number of so-called ischemic viable myocardium and is the best possible response, suggesting there will be functional recovery after revascularization. This is especially true when viability, referred to as a biphasic response, is observed in four or more segments that are akinetic at rest in patients with LV systolic dysfunction. Generally, this group of patients shows better responses to myocardial revascularization, including improvement in ejection fraction, compared to those who only show improvement in contractility at both low and high doses of dobutamine (sustained improvement) or those who show worsening of contractility in hypokinetic regions at low-dose pharmacological stress<sup><xref ref-type="bibr" rid="B214">214</xref>,<xref ref-type="bibr" rid="B215">215</xref></sup> (<xref ref-type="fig" rid="f61">Figure 20.1</xref>).</p>
          <fig id="f61">
            <label>Figure 20.1</label>
            <caption>
              <title>Summary algorithm for management of hibernating myocardium. CABG: coronary artery bypass graft; LVEF: left ventricular ejection fraction; OMT: optimal medical therapy.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
        </sec>
        <sec>
          <title>20.2. Assessment of Myocardial Viability by Longitudinal Strain</title>
          <p>Assessing myocardial viability through analysis of global longitudinal strain (GLS) of the left ventricle on two-dimensional (2D) echocardiography is an active, relevant area of research. Measuring strain and strain rate (SR) by echocardiography is a challenging but promising technique for the assessment of resting ventricular function, myocardial viability, and ischemia during stress testing. At low doses of dobutamine, there is an increase in strain and strain rate in viable segments and a reduction in post-systolic shortening. Conversely, in segments with transmural involvement after infarction, there is only a slight, transient increase in SR, with no increase in GLS, and post-systolic shortening is increased rather than reduced. <xref ref-type="fig" rid="f62">Figure 20.2</xref> summarizes the main changes seen in echocardiographic myocardial deformation analysis.<sup><xref ref-type="bibr" rid="B215">215</xref>-<xref ref-type="bibr" rid="B217">217</xref></sup> Despite interesting findings which add information to the method, studies are still needed to confirm the clinical benefit of guiding therapy on the basis of incremental myocardial deformation data; therefore, GLS still cannot replace existing techniques.</p>
          <fig id="f62">
            <label>Figure 20.2</label>
            <caption>
              <title>Main changes in myocardial deformation analysis by global longitudinal strain for assessment of myocardial viability.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <p>Regardless of the clinical decision for surgical revascularization or medical treatment, the presence and extent of viable segments demonstrate a basis for therapeutic response such as cardiac resynchronization therapy or pharmacotherapy, not only myocardial revascularization.<sup><xref ref-type="bibr" rid="B218">218</xref></sup></p>
          <p>Therefore, patients with viable myocardial segments will have a better therapeutic response and a better prognosis when undergoing clinical or surgical interventions.</p>
        </sec>
      </sec>
      <sec>
        <title>21. Stress Echocardiography with Ultrasound Enhancing Agents for Delineation of the Endocardial Border</title>
        <p>Ultrasound enhancing agents (UEAs) &#8211; the more recent nomenclature for microbubble or ultrasound contrast &#8211; can and should be used in all stress modalities.</p>
        <p>In treadmill stress tests, images are obtained at rest and immediately after exertion (ideally up to 90 seconds after the cessation of exercise, at which time the patient lies down and the images are acquired). When using a reclining or cycle ergometer, images are obtained continuously throughout the various stages of exertion, just as in pharmacological stress echocardiography. Therefore, the administration of UEAs differs according to the type of stressor.</p>
        <p>It is well known that some patients lack a satisfactory echocardiographic window, which can compromise the quality and interpretation of the examination. In these cases, the use of UEAs, which allow perfect visualization of the borders of the walls of the heart, is essential. Detailed visualization of all segments is essential for the detection of CAD. Visualization of all segments at rest and during stress is also important to determine the extent of induced ischemia or the presence of previous infarction.<sup><xref ref-type="bibr" rid="B219">219</xref>,<xref ref-type="bibr" rid="B220">220</xref></sup></p>
        <p>Currently, there is a trend to avoid referring to these agents as "contrast agents" so as not to associate them with those used in conventional radiology or magnetic resonance imaging, which have infinitely greater toxic and allergenic potential than the agents used for ultrasound.<sup><xref ref-type="bibr" rid="B221">221</xref></sup> For this reason, we will use the acronym UEA instead, as described above.</p>
        <p>Stress echocardiography with UEA exhibits greater sensitivity, specificity, and diagnostic accuracy.<sup><xref ref-type="bibr" rid="B222">222</xref>,<xref ref-type="bibr" rid="B223">223</xref></sup></p>
        <p>Furthermore, UEAs can be cost-effective when used with appropriate indications, especially when two or more segments are poorly visualized on apical views,<sup><xref ref-type="bibr" rid="B223">223</xref></sup> thus avoiding the use of other imaging modalities with higher cost and potential for renal toxicity or radiation exposure.</p>
        <sec>
          <title>21.1. Ultrasound Enhancing Agents</title>
          <p>As of the time of writing, only one UEA is registered and therefore available for use in Brazil: Sonovue (Bracco), which is composed of microbubbles generated from sulfur gas. These bubbles mostly have a diameter of &lt; 5 micrometers and thus pass through the pulmonary capillaries, rapidly (in about 2 seconds) reaching the left side of the heart and delineating the borders of the left ventricular walls. These agents improve image quality and confidence in the interpretation of examination findings.<sup><xref ref-type="bibr" rid="B219">219</xref>-<xref ref-type="bibr" rid="B222">222</xref></sup></p>
          <p>There is a wealth of literature corroborating the safety of UEAs. Nevertheless, the potential for anaphylactoid reactions &#8211; although exceedingly rare &#8211; mandates the immediate availability of medications and equipment for cardiopulmonary resuscitation.<sup><xref ref-type="bibr" rid="B223">223</xref></sup></p>
          <sec>
            <title>21.1.1. Administration</title>
            <p>Most modern echocardiography equipment features specific presets for UEA delineation of the endocardial border and ventricular cavity opacification (rather than for perfusion assessment). Although UEAs can be administered as a bolus or continuous infusion, we believe the bolus method is more practical and yields excellent results. Enough UEA should be administered to opacify the heart homogeneously, without causing swirling at the apex or attenuation at the base. The echocardiographer should always use the device's factory-set UEA protocols, which should feature a low mechanical index (MI) (&lt; 0.3), harmonics, or a nonlinear pulse sequence.<sup><xref ref-type="bibr" rid="B224">224</xref>,<xref ref-type="bibr" rid="B225">225</xref></sup> In more modern systems, a very low MI (&lt; 0.2) avoids destruction of the microbubbles, enhances the microbubble signal, and reduces artifacts, allowing for excellent delineation of the endocardial borders.</p>
            <p>Some echo labs use UEAs in all SE examinations to improve accuracy; however, cost-effectiveness is questionable in this setting, since in many centers only around 20% of cases appear to actually require such enhancement.</p>
            <p>During pharmacological stress associated with UEA, contrast-specific stress presets are used for endocardial border delineation. When we wish to evaluate perfusion (which depends on specific, more sophisticated software, not the same used for endocardial border analysis), we switch from the endocardial border delineation preset to the appropriate preset for myocardial perfusion (pulse inversion, power modulation, or cadence pulse sequencing). It is worth noting that myocardial perfusion analysis requires specialist expertise and a greater learning curve than endocardial border analysis.</p>
            <p>For UEA use, a Jelco-type peripheral IV catheter with a 2-way infusion extension set or, preferably, a 2-way stopcock, leaving one of the lines in a straight line for the administration of the UEA. The UEA is administered before the start of the test (for baseline image acquisition) and before/during each step of the stress protocol, to ensure comparable images are obtained. For the first injection, we administer a bolus of approximately 0.5 mL, which may or may not be followed by a slow saline flush (rapid administration of the UEA bolus and/or saline flush will cause hyperechoic signal, with shadowing in the mid-distal regions of the heart). During the various stages of dobutamine infusion, we no longer perform a saline flush after each bolus.</p>
            <p>During treadmill SE, we prefer to place the IV line in the patient's left upper extremity (preferably the antecubital fossa). As per our institutional protocol, the UEA is administered approximately 15-20 seconds before peak exertion and before the patient is moved to the examination table for acquisition of immediate post-exercise images. Here, again, there is no need to flush the line after administering the UEA. Baseline images are obtained as soon as the patient lies on the examination table.</p>
            <p>Quad-screen mode than places the images side by side to allow perfect interpretation. Ideally, the UEA should therefore be administered at every step of the stress protocol (<xref ref-type="fig" rid="f63">Figure 21.1</xref>).</p>
            <fig id="f63">
              <label>Figure 21.1</label>
              <caption>
                <title>Side-by-side echo images in quad-screen format, allowing for perfect interpretation of the different stages of the examination.</title>
              </caption>
              <graphic xlink:href=""/>
            </fig>
            <p>It is worth noting that, when using UEAs in stress echocardiography, the ideal approach is to begin acquiring images from the apical view. This window may even be the only one used to obtain images of all left ventricular walls, because the left ventricular apex should be well opacified and is the area most affected by the destruction of bubbles caused by insonation; therefore, it should be examined first.</p>
          </sec>
        </sec>
      </sec>
      <sec>
        <title>22. Stress Echocardiography with Ultrasound Enhancing Agents for Myocardial Perfusion Analysis</title>
        <p>The volume of blood in the coronary circulation is mostly (about 90%) found within the capillaries. Just as UEAs opacify the left ventricular cavity upon insonation, microbubbles within the capillaries cause a speckled intramyocardial appearance. The intensity of this brightness thus correlates with the volume of blood within the microvascular system.</p>
        <p>Following UEA administration, myocardial perfusion (MP) is assessed in all three apical views of the left ventricle. This can be done either during continuous infusion of the agent or, more routinely, after bolus injections.</p>
        <p>When performing concomitant analysis of myocardial contraction and perfusion, the microbubble destruction-replenishment method is used, employing a very low MI, especially when using specific software for real-time perfusion analysis (MI &lt; 0.2), as is currently considered optimal (rather than standard endocardial border delineation software). The replenishment technique is important for determining the rate of myocardial wall refilling and the presence or absence of ischemia.</p>
        <p>After administration of the UEA, as soon as adequate LV opacification is achieved, a high-energy pulse (flash; high MI: 0.8 &#8211; 1.2)<sup><xref ref-type="bibr" rid="B226">226</xref></sup> is delivered, which will destroy the microbubbles in the intramyocardial capillary blood volume while relatively sparing any intracavitary microbubbles. If there is limiting obstruction of coronary flow in the epicardial arteries and/or microcirculation, the end result is attenuation or even absence of myocardial brightness in the affected segment. (<xref ref-type="fig" rid="f64">Figure 22.1</xref>).</p>
        <fig id="f64">
          <label>Figure 22.1</label>
          <caption>
            <title>A 60-year-old woman undergoing dobutamine stress echocardiography with ultrasound-enhancing agent. She presented with chest discomfort and ST segment depression in precordial leads on the ECG tracing. Note the area of impaired myocardial perfusion at the apex of the left ventricle, with local hypokinesis (arrows). Stress echocardiography positive for apical myocardial ischemia.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>This analysis is routinely performed during the examination; however, offline analysis has proven superior because it allows objective assessment of the two components that make up MP: capillary blood volume (component &#945;) and capillary blood velocity (component &#946;). MP is determined by the product of these 2 components (&#945; &#215; &#946;), as demonstrated in <xref ref-type="fig" rid="f65">Figure 22.2</xref>. A reduction in the &#945; component may be related to infarcted areas or significant restriction of microvascular flow, while a decrease in the &#946; component correlates with reduced capillary flow, associated with obstructive CAD or MINOCA. In MINOCA, there is a delay and MP deficit, but with preserved myocardial thickening, since there is no subendocardial involvement.<sup><xref ref-type="bibr" rid="B227">227</xref></sup> The diagnosis is made by perfusion-contraction analysis, where MP and regional wall motion are evaluated together, as well as by demonstrating a microvascular flow reserve &lt;2, preferably determined on vasodilator stress echocardiography.<sup><xref ref-type="bibr" rid="B228">228</xref>,<xref ref-type="bibr" rid="B229">229</xref></sup> The &#946; component has greater sensitivity than the &#945; component for detecting CAD.<sup><xref ref-type="bibr" rid="B230">230</xref></sup> As a general rule, normal MP is based on myocardial refill (full restoration of the signal measured in decibels) in under 5 seconds at rest (for a heart rate of 60 bpm) or in up to 2 seconds during stress (for a heart rate of 120 bpm). This analysis should be performed at end-systole.<sup><xref ref-type="bibr" rid="B230">230</xref></sup></p>
        <fig id="f65">
          <label>Figure 22.2</label>
          <caption>
            <title>Example of offline myocardial perfusion analysis. Apical 2-chamber view of the LV. Note extensive perfusion deficit on the anterior wall (red). A, capillary blood volume analysis (&#945; component). B, capillary blood velocity analysis (&#946; component). C, microvascular blood flow analysis (&#945; &#215; &#946;).</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>MP assessment significantly enhances the conventional subjective assessment of myocardial regional wall motion/thickening (the cornerstone of stress echocardiography), thus increasing the sensitivity of the method for detecting CAD, as demonstrated by several studies.<sup><xref ref-type="bibr" rid="B231">231</xref>-<xref ref-type="bibr" rid="B233">233</xref></sup> It also compares favorably to SPECT scintigraphy in terms of sensitivity for detecting obstructive CAD.<sup><xref ref-type="bibr" rid="B234">234</xref></sup> One of the reasons is precisely the fact that nuclear perfusion imaging assesses capillary blood volume alone,<sup><xref ref-type="bibr" rid="B235">235</xref></sup> while echocardiographic analysis of MP also allows evaluation of capillary blood flow velocity, which is known to be a more sensitive marker for detecting CAD.<sup><xref ref-type="bibr" rid="B230">230</xref></sup></p>
        <p>Accuracy studies for CAD detection have shown that stress echocardiography combined with MP analysis has a sensitivity of 83% and specificity of 79% with vasodilator protocols<sup><xref ref-type="bibr" rid="B236">236</xref>,<xref ref-type="bibr" rid="B237">237</xref></sup> and a sensitivity and specificity of 88% and 77%, respectively, when using dobutamine or physical stress.<sup><xref ref-type="bibr" rid="B237">237</xref></sup></p>
        <p>In addition to enhancing detection of CAD, SE analysis of myocardial perfusion is a good prognostic indicator. A properly performed stress test negative for myocardial ischemia, coupled with MP analysis demonstrating normal perfusion, carries an excellent prognosis, with a very low incidence of major adverse cardiovascular events or death in the short to medium term.<sup><xref ref-type="bibr" rid="B238">238</xref></sup> Myocardial perfusion imaging is also superior to clinical data and LVEF for predicting ventricular remodeling over time.<sup><xref ref-type="bibr" rid="B239">239</xref></sup></p>
        <p>MP analysis can also assist in assessing myocardial viability. Histologically, the basis for the viability of myocardial tissue (and, thus, the possibility of functional recovery) lies in the relationship between the density of microvascularization and the quantity and extent of tissue collagen (fibrosis). Therefore, extensive areas of marked perfusion deficit denote transmural involvement and reduced myocardial viability, a finding comparable to those of CMR using gadolinium contrast.<sup><xref ref-type="bibr" rid="B240">240</xref>,<xref ref-type="bibr" rid="B241">241</xref></sup></p>
        <p>Recommendation:</p>
        <list list-type="bullet">
          <list-item>
            <p>In echo labs having staff trained to perform it, the incorporation of contrast echocardiography with myocardial perfusion analysis to stress echocardiography adds power to identify and stratify obstructive CAD;</p>
          </list-item>
          <list-item>
            <p>Myocardial perfusion analysis can aid in analyzing the myocardial viability of segments that clearly do not show improved contractility with administration of dobutamine.</p>
          </list-item>
        </list>
      </sec>
      <sec>
        <title>23. Stress Echocardiography with Myocardial Strain Imaging in Ischemic Heart Disease</title>
        <p>The introduction of speckle-tracking echocardiography (STE) has enabled the quantitative assessment of myocardial deformation (or strain) during stress echocardiography. Strain imaging provides a novel approach to assessment of myocardial function that is both objective and quantitative, and has several advantages over conventional echocardiography. The aim of this chapter is to provide an overview of the current state of knowledge regarding the utility of GLS (global longitudinal strain) and RLS (regional longitudinal strain) analysis in stress echocardiography, with particular focus on ischemic heart disease.</p>
        <sec>
          <title>23.1. Speckle Tracking-Derived Strain Versus Tissue Doppler-Derived Strain During Stress Echocardiography</title>
          <p>As previously mentioned, SE is used to assess CAD by inducing physiological stress on the heart through exercise or pharmacological stimulation with dobutamine or dipyridamole. Comprehensive imaging, which includes assessment of myocardial strain, has been shown to improve the accuracy of SE for CAD diagnosis and prognosis.</p>
          <p>Tissue Doppler imaging and its derived parameters, such as myocardial strain and strain rate, have provided alternative approaches to quantify regional wall motion at rest or during stress with greater accuracy.<sup><xref ref-type="bibr" rid="B49">49</xref>,<xref ref-type="bibr" rid="B242">242</xref></sup> Tissue Doppler is feasible during stress testing, but requires a high frame rate of at least 140 frames per second. Its main limitation is that the peak velocity and strain variables depend on the angle between the incident ultrasound beam and the myocardial wall; therefore, the apical region is not evaluable<sup><xref ref-type="bibr" rid="B243">243</xref></sup> through Doppler imaging.</p>
          <p>Non-Doppler 2D strain imaging is a novel echocardiographic technique used to measure strain and strain rate. It employs a two-dimensional analysis of motion by plotting points on the ultrasound image.<sup><xref ref-type="bibr" rid="B244">244</xref></sup></p>
          <p>Currently available software allows for the spatial and temporal processing of images, as well as the recognition and selection of these points (unique fingerprints of the heart, known as "speckles") on the echo image. The displacement of each cluster of speckles (pixels) represents local tissue motion. Tracking these pixels allows calculation of tissue velocity, strain, and strain rate using 2D ultrasound. Non-Doppler 2D strain imaging is a simple procedure that requires acquisition of only one cardiac cycle and can be easily processed and interpreted after data acquisition.<sup><xref ref-type="bibr" rid="B245">245</xref></sup></p>
          <p>Ischemia is defined as a regional reduction in myocardial thickening, which can also result in a delay in the onset and termination of systolic contraction.</p>
          <p>It bears stressing that ischemia is not only a spatial phenomenon, but also a temporal one; experimentally, with a coronary occlusion time of 40 seconds, myocardial thickening not only decreases but is delayed and continues into the post-ejection or diastolic period (a phenomenon known as tardokinesis, post-systolic contraction, or post-systolic strain).</p>
          <p>Unfortunately, the human eye does lack sufficient temporal resolution to detect subtle contractile changes in real time. Conversely, strain can be automatically tracked during the cardiac cycle by measuring the distance between two pixels on a myocardial segment. Numerous small, clustered regions of myocardial speckles (kernels) are tracked, and the software averages their movements before extracting regional curves and the global average. The quality of tracking can be checked for each segment, with manual adjustment of the region if necessary. This novel method allows for the simultaneous evaluation of the three components of myocardial strain: radial, longitudinal, and circumferential. In practice, apical views are used to obtain the GLS and strain rate, while parasternal short-axis views are used to evaluate radial and circumferential strain.<sup><xref ref-type="bibr" rid="B246">246</xref></sup></p>
          <p>Hanekom et al. compared the use of 2D strain versus tissue Doppler imaging for detecting ischemia during dobutamine stress echocardiography in 150 patients. They found that speckle tracking was a feasible means of measuring strain during DSE and had similar accuracy to tissue Doppler in detecting ischemia in the LAD territory. However, 2D deformation was not as accurate as tissue Doppler in detecting ischemia in the territories supplied by the circumflex and right coronary arteries.<sup><xref ref-type="bibr" rid="B247">247</xref></sup></p>
          <p>In practice, there is no competition between Doppler-based strain and speckle tracking-based 2D strain imaging; rather, they supplement one another, each having its own advantages and limitations. Doppler-based strain imaging should be used with higher heart rates, lower-quality windows, and to assess basal and medial velocities, and 2D strain imaging when wishing to prioritize accuracy and apical analysis of the left ventricle (LV). Two-dimensional strain is recommended for heart rates between 40 and 100 bpm, high-quality acoustic windows, and for longitudinal and circumferential assessment of the LV, as well as rotation and torsion, prioritizing the automatic nature of analysis and shorter study time.</p>
        </sec>
        <sec>
          <title>23.2. Two-Dimensional Strain During Stress Echocardiography: Diagnostic and Prognostic Value in Coronary Artery Disease</title>
          <p>Reant et al. investigated the applicability of 2D strain for detecting ischemia during dobutamine stress echocardiography in swine. The main results of the study demonstrated that 2D strain is as reliable as sonomicrometry for assessing regional LV function. The authors demonstrated that longitudinal and circumferential abnormalities precede a decrease in radial strain in the presence of ischemia. This finding can be explained by the fact that subendocardial myocardial fibers are primarily oriented longitudinally, which makes longitudinal function more sensitive to ischemia and, therefore, is affected earlier than radial function.<sup><xref ref-type="bibr" rid="B248">248</xref></sup></p>
          <p>Elamragyy et al. conducted a prospective study of 101 patients with an intermediate probability of CAD risk. The patients were evaluated by DSE and speckle-tracking imaging. All underwent coronary angiography within 1 month. The sensitivity and specificity of DSE for detecting coronary artery disease were 79.6% and 92.3%, respectively. By adding a GLS cutoff of &#8804; &#8722;20.5, the sensitivity and specificity for diagnosis of CAD increased to 95.9% and 84.6%, respectively.<sup><xref ref-type="bibr" rid="B249">249</xref></sup></p>
          <p>Other authors have also demonstrated that GLS measured during DSE had greater sensitivity but lower specificity compared to analysis of regional wall motion abnormalities.</p>
          <p>Of particular interest is a study by Uusitalo et al., which evaluated strain and post-systolic index in 50 patients with intermediate risk for CAD after dobutamine infusion during the initial recovery phase. The results showed an increase in the diagnostic accuracy of the examination. Among patients with CAD, strain was &#8722;16.4 &#177; 4.8 compared to &#8722;19.3 &#177; 3.9 in healthy individuals (p &lt; 0.001), with a significant increase in post-systolic index.<sup><xref ref-type="bibr" rid="B250">250</xref></sup></p>
          <p>The results of the Uusitalo study suggest that incorporating strain and post-systolic index measurements during early recovery after infusion of 20 mcg/kg/min of dobutamine may improve the diagnostic accuracy of DSE in patients at intermediate risk for CAD.</p>
          <p>Although viability assessment remains controversial, there is a large body of literature that supports the idea that the behavior of GLS and SPI can be used to recognize viable myocardium based on its response to low-dose dobutamine.</p>
          <p>Strain imaging during DSE is easier to perform compared to exercise echocardiography because it is less affected by respiratory motion. DSE also allows for more consistent image acquisition due to the stable increase in heart rate and contractility, which can improve the accuracy and reliability of myocardial strain measurements.</p>
          <p>Strain imaging during DSE has been extensively studied, but results regarding viability and applicability of imaging obtained during exercise echocardiography are still lacking. This may be due to technical difficulties associated with image acquisition during exercise, as well as to increased patient movement and respiratory artifacts, which can affect the accuracy of strain measurements.</p>
          <p>Currently, there is little data &#8211; and only from small series &#8211; comparing conventional image acquisition versus GLS and RLS measurement during stress echocardiography on a treadmill or reclining ergometer.</p>
          <p>The feasibility of speckle-tracking during exercise stress echocardiography was evaluated in 67 healthy adult patients, with satisfactory results. The study stratified patients by age group and sex, with groups divided into 23-to-35, 35-to-55, and 55-to-80 years old. The results showed that GLS increased significantly during exercise across all age groups, regardless of sex. The mean absolute increase in GLS was 5.3%.<sup><xref ref-type="bibr" rid="B251">251</xref></sup> This suggests that strain echocardiography may be a useful tool for assessment of cardiac function during stress testing.</p>
          <p>Currently, it is possible to demonstrate, in patients with a good acoustic window, high feasibility of GLS assessment at rest (99%) and in the immediate (&lt;30 s) post-exercise period (97.5%) on a reclining ergometer; the absence of increase or decrease in longitudinal strain of the apical segments was consistent with the presence of visually detected ischemia in 78.6% of examinations, while apical longitudinal strain increased in 96.2% of cases negative for ischemia according to standard subjective assessment of regional wall motion abnormalities.</p>
          <p>However, strain analysis was only reliable for segments irrigated by the LAD. Therefore, 2D strain analysis was feasible in the immediate post-exercise period, but high heart rates led to nonspecific findings in the mid- and basal inferolateral segments.<sup><xref ref-type="bibr" rid="B252">252</xref></sup></p>
          <p>Key reasons why only the apical segments could be analyzed reliably may include: 1) 2D axial resolution is generally very good; 2) lateral resolution decreases as depth of field increases. If the lateral resolution is low, the consequence is a "blurred" image that does not allow speckles to be tracked as easily in distant fields; 3) translational movement of the heart during exercise increase the difficulty of tracking the basal and mid-cavity segments; and 4) at elevated heart rates, frame-to-frame changes are abrupt and angular independence begins to be lost with a lower line (and information) density, which remains sufficient for tracking in the near field, but is insufficient for distant fields.<sup><xref ref-type="bibr" rid="B252">252</xref></sup></p>
          <p>Dipyridamole stress echocardiography is one of the several protocols recommended for diagnostic and prognostic elucidation of CAD. However, its use in the echo lab is not widespread, not for truly scientific reasons but rather due to a lack of knowledge or for personal, geographical, or economic reasons, as well as limited availability. Given at high doses over rapid infusion times with the addition of atropine and/or isometric handgrip exercise, dipyridamole provides a level of diagnostic accuracy comparable to that of dobutamine, with a three times lower rate of serious complications.<sup><xref ref-type="bibr" rid="B57">57</xref>,<xref ref-type="bibr" rid="B253">253</xref></sup></p>
          <p>In a retrospective study by Lowenstein-Haber D et al. involving 150 patients referred for dipyridamole stress echocardiography, apical and LAD coronary reserve were assessed and visual analysis of regional wall motion was performed.<sup><xref ref-type="bibr" rid="B254">254</xref></sup> Abnormal regional apical longitudinal strain and low coronary reserve during dipyridamole stress were the only predictors of worse outcomes, regardless of visual analysis of regional wall motion abnormalities.</p>
          <p>A previous report from the same group also demonstrated that 2D strain analysis significantly improved the sensitivity of dipyridamole stress echocardiography for detecting coronary artery disease compared to standard analysis of myocardial contractility (83.3% vs. 50%; p = 0.001), without compromising specificity (100%).<sup><xref ref-type="bibr" rid="B255">255</xref></sup></p>
          <p>Identical conclusions were drawn in investigations by other groups, which have also proven the added value of measuring two-dimensional strain alongside conventional visual analysis of regional wall motion.</p>
        </sec>
        <sec>
          <title>23.3. Which Strain is Most Useful in stress echocardiography? Global or regional? Longitudinal or Circumferential? And What is the Importance of Post-Systolic Thickening?</title>
          <p>Most studies that evaluated the feasibility and accuracy of GLS assessment during exercise stress echocardiography were performed on small groups of healthy individuals.</p>
          <p>Although RLS analysis can provide more detailed information about specific areas of the heart, it can also be technically more difficult and complex to perform and interpret. On the other hand, GLS provides a more complete assessment of overall myocardial function and has been shown to be a powerful predictor of adverse cardiovascular outcomes.</p>
          <p>However, it is also important to note that simply observing the magnitude of strain may not reflect the entirety of the situation. The timing of peak strain, both global and regional (percent post-systolic contraction and deformation), and measures of mechanical dispersion are of paramount importance and can provide information about abnormalities in myocardial mechanics, as can be seen in the following example (<xref ref-type="fig" rid="f66">Figures 23.1</xref> and <xref ref-type="fig" rid="f67">23.2</xref>).</p>
          <fig id="f66">
            <label>Figure 23.1</label>
            <caption>
              <title>A 50-year-old man with positive risk factors reported interscapular pain at the onset of exercise. Note decrease in strain and post-systolic deformation at peak exertion (white arrows). Coronary angiography: 2 significant blockages along the left anterior descending artery.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <fig id="f67">
            <label>Figure 23.2</label>
            <caption>
              <title>Little increase in global strain with dobutamine stress, but marked dispersion of the curves and post-systolic contraction are indicative of ischemia. Upper left corner: polar map showing a baseline strain of 21.6%. Middle: Strain during dobutamine stress is 21.4%. Right: Strain during recovery is 20.8%. Midline: In blue, the percentage of post-systolic strain that increased sharply with low-dose dobutamine. Below the respective curves. Patient with severe triple-vessel coronary artery disease.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <p>Dipyridamole stress echocardiography is an excellent modality for simultaneously assessing regional wall motion and the behavior of GLS and SPI, adding diagnostic and prognostic information. GLS and RLS measurement added to dobutamine stress increases its accuracy for detecting myocardial viability, and strain rate assessment by M-mode Doppler can be very helpful in visualizing the post-systolic shortening phenomenon, which can also be visualized in the curves and target with 2D strain showing dyssynchrony/ischemia if it occurs during the test.</p>
          <p>Establishing normal values for myocardial strain during stress echocardiography in healthy individuals can help better interpret strain data in patients with suspected cardiovascular disease.<sup><xref ref-type="bibr" rid="B256">256</xref></sup></p>
          <p>LV GLS is not homogeneous; there is a gradient from the basal segments to the apex, known as the basal-to-apical gradient. This gradient is observed in both circumferential and longitudinal strain, with lower values in the basal segments and higher values at the apex. A gradient between the subendocardium and the epicardium has also been found.</p>
          <p>Although the literature provides reference values for apical, mid-cavity, and basal segments, the lack of homogeneity in regional strain significantly complicates subsequent analyses. Nevertheless, regional strain analysis can help confirm ischemia in stress echocardiography.</p>
          <p>Three short-axis views at the basal, mid-cavity, and apical levels should be used to assess circumferential strain and twist and torsion. However, acquiring an apex view identical to the baseline (resting) image is not always feasible during stress echocardiography, making it less suitable for this type of assessment.</p>
        </sec>
        <sec>
          <title>23.4. Does Strain Have Ischemic Memory?</title>
          <p>In a study of 101 segments exhibiting behavior deemed ischemic on visual analysis, the mean GLS at rest was &#8722;22.3 &#177; 4.3%; at peak exercise, it decreased significantly to &#8722;16 &#177; 3.2%; 3 minutes after recovery, values were higher than those obtained at rest (-24.3 &#177; 5.1%). Thus, changes in GLS and SPI did not persist after recovery of the visually detected regional wall motion abnormalities.<sup><xref ref-type="bibr" rid="B257">257</xref></sup></p>
          <p>This behavior is consistent with the findings of an experimental study from the University of Osaka, which demonstrated that the recovery of strain and strain rate was rapid and complete relative to occlusion time. However, post-systolic indices were slower to recover.</p>
          <p>The authors conclude that if analysis of GLS and SPI is performed several minutes after exercise at heart rates below 100 bpm, when there are no more derangements of contractility, and if the ischemia time was short, strain recovers rapidly, even at supranormal values (<xref ref-type="fig" rid="f68">Figures 23.3</xref> and <xref ref-type="fig" rid="f69">23.4</xref>).</p>
          <fig id="f68">
            <label>Figure 23.3</label>
            <caption>
              <title>A 57-year-old woman with stable angina. Normal global longitudinal strain at rest with multiple, extensive dyssynergies at low workload, deterioration of peak longitudinal strain, and significant post-systolic strain. Coronary angiography: Severe distal obstruction of the left main; severe obstructions of the left anterior descending artery, right coronary artery, and circumflex artery. Rest global longitudinal strain: 19.5% Stress: 9.5%.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <fig id="f69">
            <label>Figure 23.4</label>
            <caption>
              <title>A 65-year-old patient. Stress echocardiography positive for ischemia in the apical, anterior septal, anterior, and inferior segments, with a global longitudinal strain of &#8722;20.7% at baseline, &#8722;12.6% at peak stress, and &#8722;21.1% in the recovery period. Coronary angiography: Severe obstruction of the right coronary and left anterior descending arteries. This case exemplifies that resting strain does not predict the outcome of stress echocardiography and has no ischemic memory.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <p>This transient behavior explains why patients with angina and no regional wall motion abnormalities exhibit resting 2D strain within the normal range outside of an anginal episode (if it is brief).</p>
        </sec>
        <sec>
          <title>23.5. Can Baseline Global Longitudinal Strain Predict Coronary Artery Disease in the Absence of Visually Apparent Wall Motion Abnormalities During Stress?</title>
          <p>There are reports in the literature that resting GLS can predict the presence of LMCA involvement and triple-vessel disease in patients without regional wall motion abnormalities. According to Jin-Oh Choi et al., global 2D strain was lower in 108 patients with triple-vessel or LMCA disease, even in the absence of regional wall motion abnormalities (with a cutoff point of &#8722;17.9%), with a sensitivity and specificity of 79% compared to normal.<sup><xref ref-type="bibr" rid="B258">258</xref></sup></p>
          <p>Montgomery reports that GLS analysis can detect moderate to severe CAD with comparable accuracy to the results of visual analysis during stress echocardiography, with a GLS &lt; &#8722;20% having an 80% negative predictive value for lesions &gt; 50% and 90% for lesions &gt; 70%.<sup><xref ref-type="bibr" rid="B255">255</xref></sup></p>
          <p>On the other hand, in a group of 124 patients without regional wall motion abnormalities at rest undergoing coronary angiography, GLS did not allow prediction of the outcome of stress echocardiography nor of the presence of significant CAD.<sup><xref ref-type="bibr" rid="B260">260</xref></sup></p>
        </sec>
        <sec>
          <title>23.6. Limitations</title>
          <p>Although 2D strain imaging during stress echocardiography has demonstrated its benefit in detecting subtle changes in left ventricular function, it has several limitations. Technical factors such as image quality, respiratory motion artifacts, and patient position can affect the accuracy and reproducibility of strain measurements. Furthermore, there is currently no standardized method for strain analysis in stress echocardiography, which may limit comparability and increase the heterogeneity of results across different studies.</p>
          <p>Although experiments have shown promising results, larger studies are needed to establish the diagnostic accuracy, sensitivity, and specificity of strain imaging in detecting myocardial ischemia during exercise.</p>
          <p>Furthermore, the integration of strain measurements with other parameters obtained during stress echocardiography, such as visual analysis of wall motion abnormalities, B-lines, diastolic reserve, contractile reserve, and chronotropic reserve &#8211; the true art of stress echocardiography &#8211; is not performed in most laboratories worldwide, despite its proven utility for various heart diseases, as demonstrated by the results of the Stress 2030 study led by Dr. Eugenio Picano et al.<sup><xref ref-type="bibr" rid="B261">261</xref></sup></p>
          <p>It is also important to keep in mind that the outcome of these new techniques is operator-dependent, and that proper technology, experience, and training are necessary for their rational use. In trained hands, using the right technology, with very good image quality, this limitation is not so critical for stress echocardiography.</p>
          <p>High heart rate makes 2D strain analysis difficult during exercise, while with high-dose dobutamine, the temporal resolution is insufficient for speckle tracking in the basal and mid-cavity segments of the myocardium.</p>
          <p>Although strain imaging has shown potential benefits in stress echocardiography, including greater accuracy in detecting myocardial ischemia and identifying subclinical left ventricular dysfunction in asymptomatic patients, much research remains to be done to fully define its role in routine clinical practice.</p>
        </sec>
      </sec>
      <sec>
        <title>24. Stress Echocardiography with Myocardial Strain Imaging Beyond Ischemic Heart Disease</title>
        <p>One of the applications of GLS during SE is the determination of contractile reserve (CR), supplementing information provided by the change in ejection fraction. The normal response is an absolute two-point increase in left ventricular GLS during stress compared to rest.<sup><xref ref-type="bibr" rid="B262">262</xref></sup></p>
        <p>In primary mitral regurgitation of moderate or greater severity without ventricular dysfunction, Magne et al. demonstrated that the absence of CR as measured by GLS during stress testing is an important, independent predictor of future cardiac events.<sup><xref ref-type="bibr" rid="B128">128</xref></sup></p>
        <p>An interesting study by Arbucci et al. demonstrated that the absence of CR as measured by GLS during exercise testing in asymptomatic patients with significant aortic stenosis was associated with a higher event rate and lower survival. Furthermore, assessment of CR by GLS was the best predictor of events compared to the traditional assessment of CR by the ejection fraction.<sup><xref ref-type="bibr" rid="B263">263</xref></sup></p>
        <p>In LFLG aortic stenosis with reduced ejection fraction, the assessment of GLS at rest and during dobutamine stress added important prognostic information to traditional echocardiographic parameters. As demonstrated by Dahou et al., a GLS of less than 9% at rest and less than 10% during stress was associated with higher mortality in both conservatively and interventionally treated patients.<sup><xref ref-type="bibr" rid="B264">264</xref></sup></p>
        <p>Distinguishing ischemic from nonischemic cardiomyopathy in the presence of significant ventricular dysfunction is challenging on SE. Anatomical assessment is often essential. However, in patients with mild or moderate LV dysfunction, sustained increases in contractility and GLS suggest the presence of nonischemic cardiomyopathy.<sup><xref ref-type="bibr" rid="B99">99</xref></sup> It is worth noting that this response is also observed in athletes during SE, generally with a supranormal increase in strain, and is of great value in distinguishing between athlete's heart and cardiomyopathy.<sup><xref ref-type="bibr" rid="B265">265</xref>,<xref ref-type="bibr" rid="B266">266</xref></sup></p>
        <p>In HCM, the measurement of GLS during SE helps identify patients at higher cardiovascular risk. In addition to the absence of CR, the presence of dyssynchrony during exercise is another relevant parameter to be analyzed in this population.<sup><xref ref-type="bibr" rid="B267">267</xref></sup></p>
        <p>The greatest difficulty in assessing GLS during SE is differentiating between pathological strain reduction and reduction secondary due to limitations inherent to the technique. Tachycardia, hyperventilation, inadequate image quality, variability in results between software programs, and operator inexperience are some of the challenges for measuring strain during SE (<xref ref-type="table" rid="t54">Table 24.1</xref>), as previously mentioned.</p>
        <table-wrap id="t54">
          <label>Table 24.1</label>
          <caption>
            <title>Limitations to global longitudinal strain measurement during stress echocardiography and potential solutions</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 style="background-color:#76B4CF">
                <th align="left" valign="middle">Problems</th>
                <th align="center" valign="middle">Solutions</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle">Additional time required for SE / need to acquire additional images</td>
                <td align="center" valign="middle">Routine use of all three apical views in the stress protocol</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">Inappropriate image quality</td>
                <td align="center" valign="middle">Proper adjustment of depth, sector width, and frame rate (&gt;60 fps)<break/> Avoid acquiring clips with heart rate variability greater than 10%<break/> Check ECG quality and avoid acquiring images during/after premature ventricular contractions</td>
              </tr>
              <tr>
                <td align="left" valign="middle">High heart rate</td>
                <td align="center" valign="middle">When performing ESE, use images obtained during immediate recovery (within the first minute after exercise cessation).</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN22">
              <p>ECG: electrocardiogram; ESE: exercise stress echocardiography.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>In non-ischemic disease, global strain is more valuable than regional strain, which facilitates its application in practice. The negative influence of tachycardia and hyperventilation on assessment of strain during physical exercise can be reduced by acquiring images at immediate recovery (up to the first minute after cessation of exercise). Dipyridamole stress, due to its lower chronotropic influence and high quality two-dimensional images, allows for much easier evaluation of GLS.</p>
        <p>Strain measurement during SE is a reality, and should be done whenever possible. Its quantitative, independent, objective nature makes this method a promising tool to be incorporated into SE.</p>
        <p>The utility of left ventricular GLS for evaluating CR has made this an important parameter, and regardless of the condition studied, absence of CR is associated with worse clinical outcomes and a higher rate of events. It is worth noting that the feasibility of CR assessment by GLS during SE has been greatest in studies using vasodilator stress, followed by dobutamine and, lastly, exercise.</p>
      </sec>
      <sec>
        <title>25. Three-Dimensional Stress Echocardiography</title>
        <sec>
          <title>25.1. Three-Dimensional Technology and its Applications in Echocardiography</title>
          <p>Three-dimensional echocardiography allows real-time visualization of 5 physical dimensions of cardiac structures, considering the 3 orthogonal planes of anatomical definition, cardiac flow images, and the temporal dimension.<sup><xref ref-type="bibr" rid="B268">268</xref>-<xref ref-type="bibr" rid="B271">271</xref></sup> It thus adds important morphofunctional information when compared to two-dimensional echocardiographic analysis.<sup><xref ref-type="bibr" rid="B268">268</xref>-<xref ref-type="bibr" rid="B271">271</xref></sup> The first experiments with 3D ultrasonography imaging date back to the 1950s, when interest was focused on observing the human orbit. The first images of cardiac structures were obtained in the 1970s. Since then, several incremental advances to 3D echocardiography have been made,<sup><xref ref-type="bibr" rid="B48">48</xref>,<xref ref-type="bibr" rid="B272">272</xref>-<xref ref-type="bibr" rid="B281">281</xref></sup> up to the current state of the art, in which real-time three-dimensional multi-angle matrix-array imaging of the heart is possible. This has become reality through the use of nanotechnology, digital structural observation, and undeniable advancements in the speed of morphofunctional analysis since the development of algorithms for matrix and voxel identification. Simultaneous real-time analysis of multiple planes of the heart is a perfect fit for stress echocardiography, enabling examinations to be performed with shorter acquisition times, high reproducibility, and less interobserver variability, while also providing structural information from new spatial projections.<sup><xref ref-type="bibr" rid="B48">48</xref>,<xref ref-type="bibr" rid="B272">272</xref>-<xref ref-type="bibr" rid="B281">281</xref></sup> Three-dimensional acquisition also reduces the issue of image foreshortening during acquisition, which can be problematic in two-dimensional echocardiography. Currently, 3D stress echocardiography can be performed using biplanar imaging guided by three-dimensional observation (full-volume) or matrix-array imaging (X-plane). Three-dimensional stress echocardiography is primarily dependent on the quality of the initial image, and is greatly enhanced by the use of UEAs. However, UEA administration can sometimes lead to a reduction in temporal resolution, which is already a limitation of 3D imaging, despite significant improvement in the delineation of endocardial borders in 3D stress studies with harmonic imaging and suboptimal quality.<sup><xref ref-type="bibr" rid="B278">278</xref></sup> For this reason, their use in conjunction with 3D stress echo is not yet widely recommended. Two-dimensional image acquisition allows analysis of a higher number of frames (higher frame rate) and assessment of myocardial perfusion (when used with ARUs); it also uses the frame rate, although lower, whereas 3D analysis allows evaluation from a larger sample volume (3D Full-volume) or real-time biplanar analysis (3D X-plane). However, 3D full-volume analysis can result in acquisition artifacts ("stitch") due to voxel translational movement, has low voxel rates and low temporal and spatial resolution, which limits analysis of myocardial perfusion. In comparison, the 3D Xplane technique has a better frame rate.</p>
          <p>New models of echocardiography systems are becoming available for clinical use, with the possibility of employing novel transducers and algorithms that allow for better image quality, with a higher three-dimensional volume rate, expanding the future applications of 3D imaging.</p>
          <p>Models for 3D stress echocardiography include 3D multiplanar analysis with simultaneous observation of the long and short axes of the left ventricle, plus volumetric data from apical views. Acquisition of 3D apical full-volume images should be performed with the transducer at the LV apex, with the patient holding their breath during acquisition to minimize potential image stitching resulting from cardiac translation, with a sampling volume large enough to analyze the entire LV but without excessive sector aperture, which results in a lower volume rate, during ECG recording. Occasionally, arrhythmias such as atrial fibrillation can cause errors in 3D analysis. Hyperventilation during image acquisition can also hinder obtaining the best image quality.</p>
          <p>In future, 3D stress echocardiography will involve the use of new image interpretation algorithms and smaller transducers, with single-beat image acquisition and a higher voxel count, leading to improved image quality (particularly of lateral images), reduce stitching, and shorten examination time.</p>
        </sec>
        <sec>
          <title>25.2. The Application of Three-Dimensional Echocardiography in Stress Echocardiography</title>
          <p>The possibility of using real-time three-dimensional imaging for stress echocardiography arises naturally when considering its advantages in capturing images and interpreting ischemic phenomena and changes in ventricular geometry.</p>
          <p>Peteiro was one of the first echocardiographers to compare the performance of 3D versus 2D echocardiography for exercise-induced ischemia,<sup><xref ref-type="bibr" rid="B282">282</xref></sup> as did Yang et al.,<sup><xref ref-type="bibr" rid="B274">274</xref></sup> using the dobutamine protocol. These initial studies demonstrated sensitivity and specificity similar to standard 2D imaging protocols, with the advantage of ease of image acquisition and shorter acquisition time with 3D echo.</p>
          <p>Badano et al.,<sup><xref ref-type="bibr" rid="B275">275</xref></sup> in a cohort of 44 patients who underwent angiography, demonstrated that the sensitivity and specificity of 3D echo were comparable to those of the 2D technique when using equipment with higher frame rates, and that 3D imaging compared favorably when analyzing apical changes in the territory of the left anterior descending artery. The authors suggest 3D dimensional echocardiography is broadly equivalent to conventional 2D echocardiography, but with advantages in some relevant aspects.</p>
          <p>We used the ease of three-dimensional imaging in stress echocardiography.<sup><xref ref-type="bibr" rid="B283">283</xref></sup> The first advantage lies in using the three-plane simultaneous method (Tri Plane), which provides apical 4-chamber, apical 2-chamber, and long-axis views. Unfortunately, this feature is not offered by all manufacturers of 3D devices. Proper device setup allows us to automatically view the other windows &#8211; with a satisfactory frame rate, typically above 30 frames per second and commonly reaching 60 frames per second &#8211; when we obtain a good quad-camera window. Obtaining only one window to view the complete frame using the 3D technique reduces the clip acquisition time to one-third, thus reducing examination time.</p>
          <p>When performing examination during the Balke exercise protocol, images can be captured at any point during exertion or after termination of exertion. Typically, images are obtained at rest, low load (20% increase in resting heart rate), peak exertion (submaximal heart rate or 85% of age-predicted maximum heart rate), and recovery. Each stage of the SE comprises only one apical window, focused on the 4-chamber view. This reduces repetitive strain on the examiner's upper limb, which is spared by avoiding rotation to acquire the two subsequent standard apical views (<xref ref-type="fig" rid="f70">Figure 25.1</xref>).</p>
          <fig id="f70">
            <label>Figure 25.1</label>
            <caption>
              <title>Single apical window allowing analysis of all walls of the left ventricle, saving examiner time and effort.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <p>We do not routinely use multislice imaging, which provides multiple cross-sectional views of the ventricle, but it can be used for cases deemed questionable based on previously acquired 3D images. The multislice technique allows millimeter-by-millimeter "cross-sections" of the LV to be obtained, providing a more detailed and thorough assessment of regional wall motion by comparing the LV contraction at each stage of the SE.</p>
          <p>Some echocardiography laboratories use a protocol that combined 2D Tri Plane acquisition with real-time 3D images, using the capture and analysis protocol of the former and analyzing images of the latter separately.<sup><xref ref-type="bibr" rid="B277">277</xref></sup> We also do this at our service, primarily when teaching the technique to novices. By handling both formats, the examiner can choose the image that best represents the changes elicited by physical or pharmacological stress. This process can aid the examiner in adapting to 3D mode, with its lower frame rate but better interpretation of volumetric changes.</p>
          <p>Obtaining 3D images requires adjustments to the echocardiography equipment to achieve the best volume rate per second. By working with the smallest possible depth of field and aperture, rates above 24 volumes per second can be achieved. The possibility of rotating the axes of the LV for more focused analysis at the apex or base, as well as rotation for analysis of regional wall motion in lateral views, allows a superior interpretation of contractility compared to conventionally acquired images (<xref ref-type="fig" rid="f71">Figure 25.2</xref>).</p>
          <fig id="f71">
            <label>Figure 25.2</label>
            <caption>
              <title>Three-dimensional imaging in stress echocardiogram.</title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <p>With its ability to acquire the entire LV volume in a single beat, real-time 3D echocardiography offers substantial promise to become the gold standard for assessment of patients with suspected CAD.</p>
          <p>Increased productivity with a shorter examination time and greater comfort for the examiner are significant advantages. The implementation and analysis of 3D imaging requires some adaptation.</p>
          <p>We believe that, for high-volume centers performing a large number of SEs, acquiring equipment capable of 3D stress imaging can be a very interesting resource to further optimizethe service dynamics.</p>
        </sec>
      </sec>
      <sec>
        <title>26. Stress Echo Cardiography in the Emergency Department: Indications and Applications</title>
        <p>Chest pain is one of the main reasons for seeking care at hospital emergency departments (EDs). In the United States alone, 7 million yearly ED visits have a presenting complaint of chest pain, with 30% of these categorized as acute coronary syndrome (ACS). It is estimated that up to 4% of patients are wrongly discharged from the ED due to atypical presentation or a nondiagnostic ECG.<sup><xref ref-type="bibr" rid="B284">284</xref></sup> In an era of rising healthcare costs, hospital stays of several days to "rule out" ACS are no longer sustainable, requiring effective assessment protocols and workflows.</p>
        <p>For patients at the extremes of the coronary risk spectrum, screening is straightforward; those with well-defined ACS are referred directly for cardiac catheterization, while those with a very low probability of coronary ischemia are discharged outright. The greatest challenge lies in those patients who have low to intermediate cardiac risk and lack clear evidence to support an ACS diagnosis, whether due to a nondiagnostic ECG or negative acute-phase cardiac biomarkers. In this non-negligible patient population, the diagnostic dilemma can be costly and often frustrating.</p>
        <sec>
          <title>26.1. Utility of Stress Echocardiography in the Emergency Department</title>
          <p>ED echocardiography allows assessment of cardiac function at rest, as well as detection of important differential causes of acute chest pain (such as aortic dissection and pulmonary embolism), significantly reducing evaluation time. The use of stress modalities, which may be pharmacological or physical depending on the patient's characteristics, provides a quick, effective, and important tool for noninvasive risk stratification.</p>
          <p>Among the main limitations of the method is image quality, which can be affected by factors such as obesity, underlying lung disease, or technical difficulties. To overcome this barrier, such as in cases with an unfavorable window and more than two segments not adequately visualized, an ultrasound enhancement agent (UEA) can be used to improve the accuracy of the examination.</p>
          <p>In 2007, the results of the ASSENCE (Assessment of cost-effectiveness of Several Strategies of Early diagnosis in patients with acute chest pain and Non-Conclusive Electrocardiogram) trial were published. This 10-center randomized clinical trial compared the cost-effectiveness of early dobutamine + atropine stress echocardiography versus standard assessment and exercise stress testing. Patients with ECGs that were not diagnostic of ACS, negative myocardial injury markers at baseline, and who were able to undergo stress testing were included. The primary objective was to assess cost-effectiveness, taking into account the length of hospital stay during initial admission and subsequent hospitalizations, inpatient and outpatient diagnostic procedures, and treatments. Secondary outcomes included the frequency of early and late major adverse cardiovascular events (MACE), readmission, and coronary revascularization. Of 110 patients in the stress echo arm, 90 (82%) were discharged outright, versus 78 of 89 (88%) in the exercise stress test arm. For these patients, overall costs over 2 months were 39% lower in the stress echo arm compared with the exercise stress test arm (US$1,029 vs. US$1,684; p = 0.005). In patients who required hospitalization, costs did not differ significantly between diagnostic strategies. Thus, the ASSENCE trial confirmed the general trend that adding imaging to non-image diagnostic strategies as standard of care is cost-effective. This cost-effectiveness has been attributed to fewer late events (none in the echo arm vs. 11% in the exercise stress arm), including readmissions, ACS, and late percutaneous intervention, after negative stress ECG.<sup><xref ref-type="bibr" rid="B285">285</xref></sup></p>
          <p>In the same year, Jeetley et al.<sup><xref ref-type="bibr" rid="B286">286</xref></sup> reported the results of a single-center, randomized clinical efficacy trial of 433 patients who had initial negative workups for ACS and were randomized to stress echocardiography or exercise stress testing. The primary outcome was the correct identification of patients at high risk for a composite outcome of cardiac death, nonfatal myocardial infarction, and revascularization. The secondary outcome was the cost of diagnosis. Pretest risk was classified using the TIMI (Thrombolysis In Myocardial Infarction) risk score. Post-test risk was considered low if test results were negative and high if they were positive, regardless of pretest risk. A significantly greater number of patients who underwent stress echocardiography were classified as low post-test risk and therefore eligible for immediate discharge compared to those undergoing exercise stress testing (77% vs. 33%; p &lt; 0.001). Additionally, a stress echocardiogram positive for high risk was more accurate than a positive exercise stress test in predicting this primary outcome (51% vs. 29%; p = 0.01). The rate of normal coronary angiographies in the positive exercise stress group was almost twice as high as in the stress echo group (39% vs. 23%). Significantly more patients undergoing exercise stress testing than patients undergoing stress echocardiography required additional diagnostic tests during the follow-up period (47% vs. 20%; p &lt; 0.001). The mean cost to diagnosis was significantly lower in the stress echo group than in the ergometry group (&#163;326 vs. &#163;495; p = 0.01), highlighting the significant "clinical and cost-effectiveness benefits" of stress echocardiography compared to exercise stress testing in patients with suspected ACS.<sup><xref ref-type="bibr" rid="B286">286</xref></sup></p>
          <p>In 2021, a task force led by the AHA, ACC, and ASE published a guideline for the assessment and diagnosis of chest pain, establishing that patients with acute, low-risk chest pain do not require additional anatomical or functional imaging studies and can be discharged to outpatient evaluation.<sup><xref ref-type="bibr" rid="B287">287</xref></sup> Transthoracic echocardiography (TTE), as mentioned above, can be used to visualize and assist in the differential diagnosis between myriad causes of acute chest pain, including acute aortic dissection, pericardial effusion, stress or catecholamine-induced (Takotsubo) cardiomyopathy, and hypertrophic cardiomyopathy, among others. Visualization of left and right ventricular function and RWMAs allows assessment of CAD risk and can aid in clinical decision-making. In intermediate-risk patients in whom ACS has been ruled out, stress echocardiography can be used to ascertain the presence and severity of ischemic heart disease, as well as for risk stratification purposes. For intermediate-risk patients with inconclusive CT angiography, stress echocardiography may also be a diagnostic alternative.<sup><xref ref-type="bibr" rid="B287">287</xref></sup></p>
          <p>More recently, in 2023, the European Society of Cardiology published guidelines for the management of ACS, in which stress echocardiography was highlighted as an important screening tool in patients with absent or uncertain elevation of biomarkers and a nondiagnostic ECG (Class of recommendation IIA, Level of evidence A)<sup><xref ref-type="bibr" rid="B288">288</xref></sup> (<xref ref-type="fig" rid="f72">Figure 26.1</xref>).</p>
          <fig id="f72">
            <label>Figure 26.1</label>
            <caption>
              <title>Flow chart adapted from the 2023 European Society of Cardiology Acute Coronary Syndrome Management Guidelines.<sup><xref ref-type="bibr" rid="B288">288</xref></sup></title>
            </caption>
            <graphic xlink:href=""/>
          </fig>
          <p>Therefore, stress echocardiography in the ED is a valuable tool for the diagnosis and management of patients with suspected ACS, especially those at intermediate risk, with a nondiagnostic ECG, and no cardiac enzyme elevation. However, it is important to consider the limitations of the technique and ensure that physicians are well-trained in its performance. It is also important that the laboratory logistics be set up to perform the test quickly, preferably within the first 24 hours, ensuring the cost-effectiveness of the method as observed in different clinical trials.</p>
        </sec>
      </sec>
      <sec>
        <title>27. Stress Echocardiography in the Heart Transplant Recipient</title>
        <p>Stress echocardiography is a diagnostic technique that can be used to reveal inducible myocardial ischemia in heart transplant recipients. Development of the atherosclerotic coronary artery disease known as cardiac allograft vasculopathy (CAV) is the leading cause of graft failure and death during the first year after heart transplantation.</p>
        <p>Coronary angiography via cardiac catheterization has been routinely used for many years to assess CAD in the cardiac allograft, but it is an invasive procedure and carries a higher risk of morbidity in heart transplant recipients.</p>
        <p>SE is capable of identifying CAV and has recognized prognostic value for this purpose. A normal stress echocardiogram with no RWMAs is sufficient to postpone invasive investigations.<sup><xref ref-type="bibr" rid="B289">289</xref></sup></p>
        <p>It has been reported in the literature that, due to surgical denervation of the cardiac allograft, some patients attain their optimal heart rate at low doses of dobutamine during SE. This occurs because heart transplant recipients exhibit an increased chronotropic response to beta-adrenergic stimulation. In other cases, usually in elderly recipients, add-on atropine will be required despite the maximum dose of dobutamine.<sup><xref ref-type="bibr" rid="B290">290</xref></sup></p>
        <p>Dobutamine has been the most widely used stressor agent in the post-transplant population, with a sensitivity of 70%&#8211;80% for detecting CAV.<sup><xref ref-type="bibr" rid="B291">291</xref></sup> Due to the blunted HR response to exercise secondary to denervation in heart transplant recipients, exercise stress protocols have very low sensitivity in these patients (15%&#8211;33%).<sup><xref ref-type="bibr" rid="B292">292</xref></sup></p>
        <p>A study by Bacal et al.<sup><xref ref-type="bibr" rid="B293">293</xref></sup> found that positive stress echocardiography was an independent predictor of cardiac events and/or death at 4-year follow-up. On the other hand, a negative dobutamine stress echocardiogram was indicative of low risk for CAV and a low incidence of adverse cardiac events.<sup><xref ref-type="bibr" rid="B294">294</xref></sup></p>
        <p>Dobutamine stress echocardiography is the most recommended method for routine surveillance of CAV during the first 5 years after heart transplantation, considering the high prevalence of this condition in cardiac graft recipients.<sup><xref ref-type="bibr" rid="B295">295</xref></sup></p>
      </sec>
      <sec>
        <title>28. Stress Echocardiography in Special Subgroups (Left Bundle Branch Block, Right Bundle Branch Block, and Atrial Fibrillation)</title>
        <sec>
          <title>28.1. Left Bundle Branch Block</title>
          <p>Left bundle branch block (LBBB) is a common condition with various etiologies, and is challenging from a diagnostic standpoint. LBBB affects myocardial contraction, LV diastolic filling, and coronary perfusion to varying degrees depending on the severity of the block and the underlying cardiac pathology.<sup><xref ref-type="bibr" rid="B296">296</xref></sup></p>
          <p>Approximately 2% of patients referred for exercise testing present with fixed or intermittent LBBB.<sup><xref ref-type="bibr" rid="B297">297</xref></sup> The prevalence of CAD in patients with LBBB ranges from 30% to 50%.<sup><xref ref-type="bibr" rid="B298">298</xref></sup> In the presence of LBBB, the ECG is not interpretable for evaluation of ischemia; in these cases, imaging is required for noninvasive investigation of CAD.</p>
          <p>Altered electrical activation interferes with septal wall movement, which can range from normal to paradoxical. In the presence of a QRS complex with a duration &lt; 150 ms, wall thickening is often normal and contractility is preserved. The paradoxical septal wall motion pattern is more commonly found when the QRS complex duration exceeds 150 ms and/or when septal fibrosis is present.</p>
          <p>Despite the greater difficulty in interpreting septal motility due to abnormal wall movement, SE is the best option for diagnosing CAD in this scenario.<sup><xref ref-type="bibr" rid="B44">44</xref>,<xref ref-type="bibr" rid="B298">298</xref></sup> It is a more specific modality than myocardial perfusion scanning,<sup><xref ref-type="bibr" rid="B44">44</xref>,<xref ref-type="bibr" rid="B299">299</xref></sup> with good sensitivity, although this sensitivity is lower for evaluating the LAD territory if septal dyskinesia/dyssynchrony is seen on baseline (resting) echocardiography.<sup><xref ref-type="bibr" rid="B298">298</xref></sup></p>
          <p>The prognostic value of SE in patients with LBBB is excellent, especially in those without prior myocardial infarction. Cortigiani et al. evaluated the predictive and prognostic value of pharmacological SE in patients with LBBB. In this study, two echocardiographic variables were associated with an increased risk of death from cardiac causes: the resting wall motion score and the change in wall motion score at peak stress. Five-year survival was 77% in the group of patients who tested positive for myocardial ischemia and 92% in the group with a normal test (p = 0.02).<sup><xref ref-type="bibr" rid="B300">300</xref></sup></p>
          <p>The diagnostic and prognostic value of SE can be improved by adding simultaneous assessment of coronary flow velocity reserve in the LAD<sup><xref ref-type="bibr" rid="B301">301</xref></sup> or assessment of myocardial perfusion with ultrasound enhancing agents.<sup><xref ref-type="bibr" rid="B302">302</xref></sup></p>
        </sec>
        <sec>
          <title>28.2. Right Bundle Branch Block</title>
          <p>Right bundle branch block (RBBB) is a common finding in the healthy general population; however, it can also be pathological, caused by conditions affecting the right branch of the bundle of His. Possible causes include trauma, structural changes, infiltrative diseases, infections, myocarditis, and CAD.</p>
          <p>RBBB is present in approximately 2% to 3% of patients with CAD.<sup><xref ref-type="bibr" rid="B296">296</xref>,<xref ref-type="bibr" rid="B297">297</xref></sup> In this scenario, its presence is an independent predictor of all-cause mortality.<sup><xref ref-type="bibr" rid="B303">303</xref></sup> The onset of RBBB in the context of ACS in particular has been significantly associated with increased in-hospital mortality, even after primary percutaneous coronary intervention.<sup><xref ref-type="bibr" rid="B304">304</xref></sup> SE is an excellent diagnostic modality for investigating CAD in this setting, as RBBB typically does not affect regional wall motion. Furthermore, it provides an efficient prognostic stratification to add-on simple resting ECG parameters, such as left anterior fascicular block. In patients with suspected CAD undergoing SE, co-occurrence of RBBB and left anterior fascicular block has been shown to be an independent predictor of mortality.<sup><xref ref-type="bibr" rid="B305">305</xref></sup></p>
        </sec>
        <sec>
          <title>28.3. Atrial Fibrillation</title>
          <p>The prevalence of atrial fibrillation (AF) is very low among young people (&lt;1% in the population under 40 years of age) but increases with age, affecting up to 17% of individuals over 80 years old.<sup><xref ref-type="bibr" rid="B306">306</xref></sup> CAD is one of the cardiovascular conditions most commonly associated with AF.</p>
          <p>Shortening of the diastolic phase in the setting of AF can cause false-positive results during exercise testing, since subendocardial perfusion is compromised. In this context, SE is an effective approach. Generally, vasodilator stress is better tolerated by these patients than dobutamine stress. Nevertheless, despite the increased chronotropic response to dobutamine infusion in patients with AF compared to patients in sinus rhythm, DSE has good diagnostic value in these patients. Hobday et al.<sup><xref ref-type="bibr" rid="B307">307</xref></sup> demonstrated that a higher percentage of patients with AF attained their target heart rate and required lower doses of atropine compared to patients in sinus rhythm. In the same study, positive results for myocardial ischemia occurred at similar rates among patients with AF and sinus rhythm, and the use of beta blockers was also similar.<sup><xref ref-type="bibr" rid="B307">307</xref></sup> Atropine, on the other hand, should be used sparingly in patients with AF due to the risk of significant increases in heart rate, potentially requiring hospitalization.</p>
          <p>New onset of AF during SE is a more common complication in patients with an arrhythmogenic substrate when dobutamine is used as the stressor agent. In a review of 26 studies on the complications of DSE, the incidence of AF was 0.9%.<sup><xref ref-type="bibr" rid="B308">308</xref></sup> In a recent retrospective assessment of 4,917 consecutive patients who underwent DSE, the main factors associated with onset of AF during the test were a history of paroxysmal AF (p = 0.02) and advanced age, with an incidence of 4% in patients aged over 80 years (p &lt; 0.0001).<sup><xref ref-type="bibr" rid="B309">309</xref></sup> Most patients revert to sinus rhythm within the first hour after onset of AF,<sup><xref ref-type="bibr" rid="B310">310</xref></sup> but administration of a beta blocker such as metoprolol is usually required.</p>
        </sec>
      </sec>
      <sec>
        <title>29. Stress Echocardiography for Preoperative Assessment Before Vascular Surgery, in Women, and in Older Adults</title>
        <sec>
          <title>29.1. Preoperative Assessment Before Vascular Surgery</title>
          <p>Patients undergoing vascular surgery have a high risk of cardiovascular events during the perioperative period. This can be attributed not only to the clinical characteristics of these patients, but also to the presence of comorbid CAD.<sup><xref ref-type="bibr" rid="B311">311</xref>,<xref ref-type="bibr" rid="B312">312</xref></sup> Furthermore, the nature and complexity of vascular interventions play a relevant role in this scenario.<sup><xref ref-type="bibr" rid="B313">313</xref></sup></p>
          <p>Therefore, preoperative stratification is paramount in these patients. The goal is to identify those who are more susceptible to cardiovascular events, enabling implementation of measures to reduce morbidity and mortality. In this context, stress echocardiography (physical or pharmacological) stands out as a noninvasive, widely available, low-cost method.</p>
          <p>SE can be used to assess functional capacity and the hemodynamic response to exertion. However, the presence of peripheral vascular disease and low functional capacity may compromise the effectiveness of exercise testing; therefore, pharmacological stress with dobutamine or dipyridamole is recommended in this subgroup of patients. The choice of pharmacological agent should be guided by availability, local experience, mechanism of action, and pre-existing vascular diseases.</p>
          <p>DSE has proven useful and safe, and can even be used safely in patients with abdominal aortic aneurysm.<sup><xref ref-type="bibr" rid="B314">314</xref></sup> Vasodilators (adenosine or dipyridamole) can also be considered a viable alternative which provides good accuracy.<sup><xref ref-type="bibr" rid="B312">312</xref></sup> However, their use is contraindicated in patients with severe bilateral carotid artery involvement.<sup><xref ref-type="bibr" rid="B313">313</xref></sup></p>
          <p>Patients with a positive stress echocardiogram have a higher incidence of cardiovascular events. Pharmacological stress echocardiography has excellent negative predictive value, in the 90&#8211;100% range, while its positive predictive value is lower, ranging from 25&#8211;45%.<sup><xref ref-type="bibr" rid="B312">312</xref></sup> The most significant predictors of adverse postoperative events in this population are presence of ischemia and a history of congestive heart failure. The heart rate at which ischemia develops during DSE can be used to stratify patients into low, intermediate, and high risk for postoperative myocardial infarction and death.<sup><xref ref-type="bibr" rid="B315">315</xref>,<xref ref-type="bibr" rid="B316">316</xref></sup></p>
          <p>The onset of new stress-induced RWMAs, whether extensive (3 or more segments) or limited (1 or 2 segments), in patients with a history of previous myocardial infarction has been characterized as an independent predictor of late cardiac events.<sup><xref ref-type="bibr" rid="B317">317</xref></sup></p>
          <p>In a meta-analysis of six noninvasive diagnostic modalities for preoperative assessment of patients undergoing vascular surgery, pharmacological stress tests showed higher overall sensitivity and specificity, with DSE demonstrating a trend towards superior diagnostic performance compared to all other modalities.<sup><xref ref-type="bibr" rid="B318">318</xref></sup></p>
          <p>In multiple studies and meta-analyses, the prognostic value of DSE was at least equal to that of myocardial perfusion scanning in predicting the occurrence of postoperative adverse events.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B311">311</xref>,<xref ref-type="bibr" rid="B319">319</xref></sup></p>
        </sec>
        <sec>
          <title>29.2. Women</title>
          <p>Cardiovascular disease (CVD) is the leading cause of death in women worldwide. Appropriate diagnosis and management remain challenging, as female patients may present with atypical symptoms and, therefore, receive inappropriate treatment.<sup><xref ref-type="bibr" rid="B320">320</xref></sup></p>
          <p>Studies have shown that women are more likely than men to develop angina as the first manifestation of CAD (47% vs. 32%) and are less likely than men to present with an acute myocardial infarction in this setting (6% vs. 10%).<sup><xref ref-type="bibr" rid="B321">321</xref></sup></p>
          <p>Stress echocardiography is a well-established, highly useful tool for the diagnostic investigation of women suspected of having CAD, as well as for risk stratification of those already diagnosed with coronary heart disease. It has sensitivity, specificity, and prognostic value, with no specific differences between the sexes.<sup><xref ref-type="bibr" rid="B322">322</xref></sup> Additionally, the diagnostic accuracy of DSE has been shown to be similar both in women with atypical pain and in cases of angina.<sup><xref ref-type="bibr" rid="B323">323</xref>,<xref ref-type="bibr" rid="B234">234</xref></sup></p>
          <p>A study by Biagini et al.<sup><xref ref-type="bibr" rid="B325">325</xref></sup> included 2,276 men and 1,105 women with suspected or known coronary artery disease. All underwent DSE and risk stratification; the outcomes of nonfatal myocardial infarction and cardiovascular death were observed over a 7-year follow-up. The results showed that DSE provides independent prognostic information in men and women alike.</p>
          <p>From a technical standpoint, it is important to note that women have a higher incidence of hypotension during DSE. Smaller ventricular chambers with a higher degree of relative hypertrophy can facilitate the development of dynamic LVOTO, leading to hypotension and premature test cessation. Furthermore, in smaller hearts, there is a higher likelihood of left ventricular cavity obliteration, which can mask subtle changes in wall motion.<sup><xref ref-type="bibr" rid="B326">326</xref></sup> In addition, chest pain can occur during dynamic LVOTO, raising doubts regarding the presence of myocardial ischemia. Although the protocol is the same, it is essential that not only regional wall motion but also the presence of an intraventricular gradient be assessed in these cases,<sup><xref ref-type="bibr" rid="B327">327</xref></sup> since anatomical and hemodynamic factors which may contribute to such an event are more prevalent in this subgroup of patients.</p>
          <p>In summary, SE plays a key role in the diagnosis and prognosis of CAD in women.</p>
        </sec>
        <sec>
          <title>29.3. Older Adults</title>
          <p>The population of patients over 65 years of age with suspected CAD is especially vulnerable and is constantly growing. A constant search for the most effective diagnostic approach is needed to ensure optimal treatment and the best possible outcomes.</p>
          <p>Physical or pharmacological stress echocardiography emerges as a key diagnostic tool for this population, combining the benefits of cardiac imaging with analysis of cardiovascular function under stress.</p>
          <p>In patients over 65 years of age, integration of information from SE (especially the left ventricular end-systolic volume and ejection fraction responses to exercise) with clinical, ECG, and resting echocardiography findings improves the ability to predict cardiac events and all-cause mortality.</p>
          <p>A study of 2,632 older adults (56% men) capable of exercise showed that SE provided additional prognostic value over clinical variables alone (age, diabetes, previous myocardial infarction, exercise stress test findings). In exercise stress echocardiography, exercise load was the best predictor of cardiac events and death.<sup><xref ref-type="bibr" rid="B327">327</xref></sup></p>
          <p>Given that inability to exercise is common in older adults due to the particularities of this age group, pharmacological stress echocardiography, particularly DSE, has been identified as a viable alternative. Biagini et al.<sup><xref ref-type="bibr" rid="B329">329</xref></sup> studied 1,434 patients aged &gt; 65 years (mean age 72 &#177; 3 years) who underwent DSE for evaluation of CAD. Presence of RWMAs was considered an independent predictor of all-cause mortality and adverse outcomes, while a normal examination correlated with a low incidence of cardiac events. Cortigiani et al.<sup><xref ref-type="bibr" rid="B330">330</xref></sup> showed that the rate of events in octogenarians was 4.5 times higher than in the younger elderly (between 65 and 69 years of age).</p>
          <p>The safety and accuracy of SE mean it has a crucial role to play in the diagnostic and prognostic evaluation of older adults, contributing significantly to the appropriate management of this patient population.</p>
        </sec>
      </sec>
      <sec>
        <title>30. Stress Echocardiography in Pediatrics: Indications and Protocols</title>
        <p>While stress echocardiography is a well-established technique in cardiology for adult patients, the low prevalence of conditions such as CAD, valvular heart disease, and cardiomyopathy in children has led to a scarcity of published data on this modality and to its unpopularity in pediatric practice. SE is not yet as widely used in pediatric patients as it is in adult patients, due to the inherent difficulties in performing the examination. Few centers offer this modality for pediatric patients, and there is little literature to support it.</p>
        <p>The use of stress greatly enhances echocardiographic assessment, providing data in a physiological environment that more closely resembles the typically active state of this age group.<sup><xref ref-type="bibr" rid="B331">331</xref></sup></p>
        <p>As in the adult population, the two key questions that SE seeks to answer are: 1) is there inducible myocardial ischemia? and 2) are there hemodynamically significant changes?<sup><xref ref-type="bibr" rid="B332">332</xref></sup></p>
        <p>As in adults, the stressor can be physical (such as treadmill, bicycle, or reclining ergometer exercise) or pharmacological (with dobutamine and, occasionally, dipyridamole).</p>
        <p>Exercise stress echocardiography (ESE) is well tolerated in the pediatric population, as it does not require IV access or sedation; however, it can only be performed in children over 6&#8211;7 years of age who are able to perform the exercise and are tall enough to walk on a treadmill or pedal a bicycle or reclining ergometer.<sup><xref ref-type="bibr" rid="B332">332</xref>-<xref ref-type="bibr" rid="B335">335</xref></sup> In both modalities, the modified Bruce protocol is generally used.<sup><xref ref-type="bibr" rid="B332">332</xref>-<xref ref-type="bibr" rid="B335">335</xref></sup> The James protocol can also be used on a bicycle or reclining ergometer.<sup><xref ref-type="bibr" rid="B333">333</xref></sup> There is no age limit for DSE; however, in children under 8 years old, deep sedation and/or general anesthesia is essential, and even in older children, conscious sedation may be required.<sup><xref ref-type="bibr" rid="B333">333</xref></sup> The protocols used are similar to those for adults.<sup><xref ref-type="bibr" rid="B333">333</xref>-<xref ref-type="bibr" rid="B336">336</xref></sup> Generally, dobutamine infusion starts at 5 mcg/kg/min and is increased in 3-minute intervals to 10, 20, 30, 40 and, eventually, up to 50 mcg/kg/min. If the target maximum HR (85% of the maximum HR for age) is not attained and the examination is thus inconclusive, a low dose of atropine (0.01 mg/kg) is administered at peak dobutamine stress. Even so, the target HR for this population is very high.</p>
        <p>Alternatively, continuous dobutamine infusion at low to moderate doses (5 to 20 mcg/kg/min) may be used to assess cardiac contractile reserve.<sup><xref ref-type="bibr" rid="B333">333</xref>,<xref ref-type="bibr" rid="B337">337</xref></sup> The standard dose of dipyridamole is 0.84 mg/kg of body weight, as in the adult protocols already described in previous sections.</p>
        <p>Adverse effects are similar to those observed in adult patients.<sup><xref ref-type="bibr" rid="B333">333</xref>-<xref ref-type="bibr" rid="B336">336</xref></sup> Complications such as sustained ventricular arrhythmias are rare; however, there is insufficient data in the literature regarding these complications in pediatric patients.<sup><xref ref-type="bibr" rid="B333">333</xref></sup></p>
        <p>The main indications for SE in pediatrics are: assessment of myocardial ischemia, early detection of myocardial dysfunction, dynamic assessment of gradients in hypertrophic cardiomyopathy, assessment of right ventricular function, pre-exercise assessment in patients with congenital heart disease,<sup><xref ref-type="bibr" rid="B332">332</xref></sup> and after heart transplantation and chemotherapy.<sup><xref ref-type="bibr" rid="B333">333</xref>,<xref ref-type="bibr" rid="B338">338</xref></sup></p>
        <p><xref ref-type="table" rid="t55">Tables 30.1</xref> and <xref ref-type="table" rid="t56">30.2</xref> describe these indications, with a summary of recently published articles.</p>
        <table-wrap id="t55">
          <label>Table 30.1</label>
          <caption>
            <title>Indications for stress echocardiography in children, adolescents, and young adults</title>
          </caption>
          <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 style="background-color:#76B4CF">
                <th align="left" valign="middle">Indication</th>
                <th align="center" valign="middle">No. pts</th>
                <th align="center" valign="middle">Age</th>
                <th align="center" valign="middle">Stressor</th>
                <th align="center" valign="middle">Findings</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle">
                  <bold>Kawasaki disease</bold>
                </td>
                <td align="center" valign="middle"/>
                <td align="center" valign="middle"/>
                <td align="center" valign="middle"/>
                <td align="center" valign="middle"/>
              </tr>
              <tr>
                <td align="left" valign="middle">Pahl et al. (1995)<sup><xref ref-type="bibr" rid="B335">335</xref></sup></td>
                <td align="center" valign="middle">28</td>
                <td align="center" valign="middle">10.7 years (median)</td>
                <td align="center" valign="middle">ESE (treadmill)</td>
                <td align="center" valign="middle">ESE detected RWMAs and was superior to ECG alone for this purpose.</td>
              </tr>
              <tr>
                <td align="left" valign="middle">Noto et al. (1996)<sup><xref ref-type="bibr" rid="B336">336</xref></sup></td>
                <td align="center" valign="middle">50</td>
                <td align="center" valign="middle">13.6 years (mean)</td>
                <td align="center" valign="middle">DSE</td>
                <td align="center" valign="middle">DSE was safe and accurate for diagnosis of coronary artery stenosis in children.</td>
              </tr>
              <tr>
                <td align="left" valign="middle">Noto et al. (2014)<sup><xref ref-type="bibr" rid="B340">340</xref></sup></td>
                <td align="center" valign="middle">58</td>
                <td align="center" valign="middle">23.8 years (mean)</td>
                <td align="center" valign="middle">DSE</td>
                <td align="center" valign="middle">DSE was useful for risk stratification and prognostic assessment.</td>
              </tr>
              <tr>
                <td align="left" valign="middle">Cardiac allograft vasculopathy<break/> Perez et al. (2022)<sup><xref ref-type="bibr" rid="B334">334</xref></sup></td>
                <td align="center" valign="middle">95</td>
                <td align="center" valign="middle">16.3 years (median)</td>
                <td align="center" valign="middle">ESE (treadmill)</td>
                <td align="center" valign="middle">Abnormal ESE was associated with &#8593; risk of CV events and death, while a normal ESE was associated with CV event-free survival.</td>
              </tr>
              <tr>
                <td align="left" valign="middle"><bold>AAOCA</bold><break/> Brothers et al. (2007)<sup><xref ref-type="bibr" rid="B341">341</xref></sup></td>
                <td align="center" valign="middle">24</td>
                <td align="center" valign="middle">24 years<break/> (median)</td>
                <td align="center" valign="middle">ESE (treadmill and bicycle)</td>
                <td align="center" valign="middle">ESE was useful for assessing ischemia and guiding postoperative care.</td>
              </tr>
              <tr>
                <td align="left" valign="middle"><bold>Status post arterial switch (Jatene) procedure</bold><break/>Chen et al. (2013)<sup><xref ref-type="bibr" rid="B342">342</xref></sup></td>
                <td align="center" valign="middle">32</td>
                <td align="center" valign="middle">16.2 &#177;2.1 (mean &#177; SD)</td>
                <td align="center" valign="middle">ESE (bicycle)</td>
                <td align="center" valign="middle">ESE demonstrated decreased contractile reserve in adolescents and young adults in the postoperative period.</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle"><bold>Childhood cancer survivors</bold><break/> Ryerson et al. (2015)<sup><xref ref-type="bibr" rid="B343">343</xref></sup></td>
                <td align="center" valign="middle">80</td>
                <td align="center" valign="middle">13 years (mean)</td>
                <td align="center" valign="middle">ESE (bicycle)</td>
                <td align="center" valign="middle">Patients showed improvement in diastolic and systolic function during exercise, suggesting an ability to compensate for mild cardiac dysfunction.</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle"><bold>Status post Ross procedure</bold><break/> Pauliks et al. (2012)<sup><xref ref-type="bibr" rid="B339">339</xref></sup></td>
                <td align="center" valign="middle">26</td>
                <td align="center" valign="middle">14.9 years (mean)</td>
                <td align="center" valign="middle">ESE (treadmill)</td>
                <td align="center" valign="middle">ESE was feasible in children, most of whom showed capacity for normal exercise.</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle"><bold>Status post ToF repair</bold><break/> Bhatt et al. (2019)<sup><xref ref-type="bibr" rid="B344">344</xref></sup></td>
                <td align="center" valign="middle">29</td>
                <td align="center" valign="middle">18.3&#177;4.83<break/> &#8595;performance during exercise<break/> 12.8 &#177; 3.26<break/> &#8593;performance during exercise<break/> (mean &#177; SD)</td>
                <td align="center" valign="middle">ESE (treadmill)</td>
                <td align="center" valign="middle">Preserved chronotropic response, more than right ventricular contractile reserve, was an important factor for exercise performance.</td>
              </tr>
              <tr>
                <td align="left" valign="middle"><bold>Obstructed right ventricular-to-pulmonary artery conduit</bold><break/>Hasan et al. (2012)<sup><xref ref-type="bibr" rid="B345">345</xref></sup></td>
                <td align="center" valign="middle">40</td>
                <td align="center" valign="middle">17 years (median)</td>
                <td align="center" valign="middle">ESE (treadmill)</td>
                <td align="center" valign="middle">ESE detected right ventricular and conduit dysfunction at peak exercise.</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle"><bold>LVOT gradient in HCM</bold><break/> El Assaad et al. (2020)<sup><xref ref-type="bibr" rid="B346">346</xref></sup></td>
                <td align="center" valign="middle">91</td>
                <td align="center" valign="middle">12 years (median)</td>
                <td align="center" valign="middle">ESE (treadmill and bicycle)</td>
                <td align="center" valign="middle">ESE proved safe and effective in identifying patients at low risk for CV events.</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN23">
              <p>HCM: hypertrophic cardiomyopathy; CV: cardiovascular; SD: standard deviation; DSE: dobutamine stress echocardiography; ESE: exercise stress echocardiography; AAOCA: anomalous aortic origin of the coronary arteries; LV: left ventricle; LVOT: left ventricular outflow tract; &#916;P: pressure gradient.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <table-wrap id="t56">
          <label>Table 30.2</label>
          <caption>
            <title>Indications for stress echocardiography in children, adolescents, and young adults (summarized)</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="middle" rowspan="4">Indications for stress echocardiography in pediatrics</td>
                <td align="left" valign="middle">Suspicion of coronary artery disease: Kawasaki disease, cardiac allograft vasculopathy, surgical procedures involving coronary translocation (such as arterial switch procedure for transposition of the great arteries), anomalous origin or course of the coronary arteries, pulmonary atresia with intact ventricular septum, hyperlipidemia, insulin-dependent diabetes mellitus, supravalvular aortic stenosis</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">Status post chemotherapy: Anthracyclines</td>
              </tr>
              <tr>
                <td align="left" valign="middle">Assessment of gradients: in hypertrophic cardiomyopathy or aortic and pulmonary stenosis</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">Assessment of hemodynamic and myocardial response in specific conditions: pulmonary hypertension, dilated cardiomyopathy, congenital heart disease, mitral and aortic regurgitation</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <p>For specific indications, protocols are adjusted to include, e.g., Doppler imaging of the atrioventricular valves to study aortic valve regurgitation or measure gradients in outflow tracts.</p>
        <p>In pediatric patients, unlike in adults, there is insufficient data on the prognostic value and clinical impact of SE in the dynamic assessment of gradients in aortic and pulmonary stenosis.<sup><xref ref-type="bibr" rid="B333">333</xref>,<xref ref-type="bibr" rid="B339">339</xref></sup></p>
        <p>Finally, SE is still a developing field in pediatric cardiology. Its integration with tissue Doppler and strain imaging has allowed for a more quantitative analysis of regional and global systolic and diastolic function in this setting, but it is still in its early stages. Cooperation between adult and pediatric cardiologists is essential for the development and implementation of protocols tailored to the specific needs of children and for this type of examination to become more widespread in pediatric practice.</p>
      </sec>
      <sec>
        <title>31. Advantages and Disadvantages of Stress Echocardiography in Pediatrics</title>
        <p>Both exercise stress echocardiography and pharmacological stress echocardiography can be used in pediatric patients.<sup><xref ref-type="bibr" rid="B33">33</xref>,<xref ref-type="bibr" rid="B99">99</xref>,<xref ref-type="bibr" rid="B347">347</xref></sup> However, the physician should consider the advantages and disadvantages of each approach in this population (<xref ref-type="table" rid="t57">Table 31.1</xref>).</p>
        <table-wrap id="t57">
          <label>Table 31.1</label>
          <caption>
            <title>Advantages and disadvantages of each stress echocardiography modality in the pediatric population</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 style="background-color:#76B4CF">
                <th align="left" valign="middle">Imaging Modality</th>
                <th align="center" valign="middle">Advantages</th>
                <th align="center" valign="middle">Disadvantages</th>
                <th align="center" valign="middle">Uses</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle">Exercise Stress Echocardiogram (ESE)</td>
                <td align="center" valign="middle">No intravenous puncture required<break/> No sedation required<break/> Able to obtain other data &#8211; ECG testing and potentially VO<sub>2</sub></td>
                <td align="center" valign="middle">Extra equipment<break/> Patient must be able to perform exercise on ergometer</td>
                <td align="center" valign="middle"/>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">Treadmill ESE</td>
                <td align="center" valign="middle">Resembles daily activities<break/> Higher Max VO<sub>2</sub><break/> May be easier to elicit ischemia</td>
                <td align="center" valign="middle">Motion artifact<break/> Rapid heart rate recovery in children<break/> Need to transfer to bed</td>
                <td align="center" valign="middle">Ischemia Assessment<break/> Outflow obstruction<break/> Contractile reserve</td>
              </tr>
              <tr>
                <td align="left" valign="middle">Cycle ESE</td>
                <td align="center" valign="middle">Multiple time points for imaging<break/> Less motion artifact<break/> Doppler imaging may be possible</td>
                <td align="center" valign="middle">Cooperation in younger children<break/> Lower heart rate<break/> Lower VO<sub>2</sub></td>
                <td align="center" valign="middle">Valvar regurgitation<break/> Atrioventricular valve stenosis<break/> Pulmonary hypertension<break/> Diastolic dysfunction</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">Pharmacologic Stress Echo</td>
                <td align="center" valign="middle">Less lung interference<break/> No need for transfer to bed<break/> Limits heart rate recovery issues</td>
                <td align="center" valign="middle">Intravenous line placement</td>
                <td align="center" valign="middle"/>
              </tr>
              <tr>
                <td align="left" valign="middle">Dobutamine stress echo</td>
                <td align="center" valign="middle">Affects both heart rate and blood pressure</td>
                <td align="center" valign="middle">Takes around 20 minutes<break/> Side effect profile: ventricular arrhythmias, hypertensive emergency, nausea/vomiting</td>
                <td align="center" valign="middle">Dynamic coronary obstruction<break/> Low dose &#8211; low-flow, low-gradient aortic stenosis</td>
              </tr>
              <tr style="background-color:#C7DFEC">
                <td align="left" valign="middle">Vasodilator stress echo</td>
                <td align="center" valign="middle">Short acting</td>
                <td align="center" valign="middle">Side effect profile: wheezing, seizure like activity, hypotension</td>
                <td align="center" valign="middle">Fixed coronary obstruction</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <p>Exercise SE offers some advantages over pharmacological SE in the pediatric population. First, there is no need to obtain IV access, which minimizes patient distress. Second, there is no need for sedation, which may be necessary for the longer study periods associated with pharmacological stress. Finally, the echocardiographer can often choose between two ergometers for the stress echocardiogram: a treadmill or a cycle ergometer.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B331">331</xref>,<xref ref-type="bibr" rid="B341">341</xref>,<xref ref-type="bibr" rid="B346">346</xref>,<xref ref-type="bibr" rid="B348">348</xref>-<xref ref-type="bibr" rid="B350">350</xref></sup></p>
        <p>Exercise SE also has several disadvantages, however. First, the additional equipment required can be limiting for some echo labs, especially since there is a need for a pediatric transducer and appropriate stress testing software. Furthermore, exercise echocardiography requires significant cooperation from the pediatric patient, regardless of the ergometer used. Pulmonary artifacts due to a physiological increase in respiratory rate may restrict echocardiographic windows during exercise in this subgroup of relatively uncooperative patients. Finally, the rapid recovery of heart rate in children may limit the ability to obtain adequate images at peak stress.</p>
        <p>There are specific advantages and disadvantages to each type of ergometer as well. Treadmill stress very closely resembles both activities of daily living and physical education workouts. It also usually allows attainment of a higher VO<sub>2</sub>, which is excellent for the purposes of the examination, as is the higher double product. The main disadvantage of treadmills is that the patient must be able to transfer quickly and safely from the treadmill to the echocardiography bed or couch, due to the rapid drop in heart rate (post-exercise recovery) in the pediatric population<sup><xref ref-type="bibr" rid="B3">3</xref></sup> and the examiner thus needs to obtain these images within a very brief window of time, which is not always easy, especially in children.</p>
        <p>Reclining ergometers allow for imaging at various time points during the stress test with continuous monitoring. Cycle ergometers may allow for a gradual and more appropriate use of color or spectral Doppler in this subpopulation, which can be advantageous when assessing valve stenosis or regurgitation and pulmonary hypertension,<sup><xref ref-type="bibr" rid="B3">3</xref></sup> intraventricular obstruction in hypertrophic cardiomyopathy, and gradients in aortic stenosis.<sup><xref ref-type="bibr" rid="B346">346</xref>,<xref ref-type="bibr" rid="B350">350</xref></sup> Furthermore, cycle ergometers tend to limit movement artifacts. However, cooperation can be more difficult in younger patients because they must pedal continuously and at a constant pace. Typically, lower VO<sub>2</sub>max and lower heart rates are achieved with cycle ergometers compared to treadmills.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
        <p>Pharmacological stress echocardiography can be performed in children.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B351">351</xref>,<xref ref-type="bibr" rid="B352">352</xref>,<xref ref-type="bibr" rid="B340">340</xref></sup> However, the main disadvantage is the need for IV access to administer the stressor agent. Advantages include less pulmonary interference, assessment at various stages of the test, and no need for transfer to a bed for imaging, thus mitigating the issues associated with rapid heart rate recovery in children, since echocardiographic monitoring is continuous during pharmacological stress.</p>
        <p>Two main pharmacological stressors are used in this population: dobutamine and vasodilators.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Dobutamine mimics exercise by increasing heart rate and blood pressure to levels close to those attained during maximal exercise. In children, it is mainly used to induce ischemia and RWMAs in areas where there may be dynamic obstruction of coronary arterial flow, in the assessment of anomalous aortic origin of the coronary arteries, and in heart transplant recipients.<sup><xref ref-type="bibr" rid="B341">341</xref>,<xref ref-type="bibr" rid="B349">349</xref>,<xref ref-type="bibr" rid="B351">351</xref>,<xref ref-type="bibr" rid="B352">352</xref></sup></p>
        <p>Vasodilators, such as dipyridamole, adenosine, or regadenoson, dilate normal coronary arteries, causing ischemia and regional wall motion abnormalities in areas with fixed coronary obstruction.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> In the pediatric population, they can be particularly useful in the assessment of Kawasaki disease and reimplanted coronary arteries. Adverse effect profiles vary depending on the vasodilator used, as described in previous sections of this guideline.</p>
        <p>Although many stress echocardiography options are available, it remains underutilized in children. Physicians who understand the advantages and disadvantages of each modality can select the most appropriate option for each clinical scenario.</p>
      </sec>
      <sec>
        <title>32. Prognostic Value of Stress Echocardiography</title>
        <p>Eliciting myocardial ischemia by increasing heart rate to &#8805; 85% of predicted for age during SE, whether through physical exercise or intravenous dobutamine infusion, is an effective method to guide clinical management and prognostication in ischemic heart disease, and this has been widely discussed in the literature. The normal response is an increase in contractility of all 16 (or 17) ventricular segments.<sup><xref ref-type="bibr" rid="B202">202</xref></sup> The response of each segment is assigned a score of 1 if normal or hyperkinetic, 2 if mildly or moderately hypokinetic, 3 if severely hypokinetic, 4 if akinetic, or 5 if dyskinetic. To streamline assessment, the following scoring system is now more commonly used: 1 = normal or hyperkinetic, 2 = hypokinetic (regardless of severity); 3 = akinetic; and 4 = aneurysm. The sum of the individual segment scores allows calculation of the WMSI, dividing all visualized segments by the 16 or 17 analyzed segments. The only possible normal result is 16/16 = 1 or 17/17 = 1, which denotes normal global contractility. An example abnormal score: moderate hypokinesis in 2 segments (score = 2 each) adds up to 4, plus akinesis in one segment (score = 4) adds up to 8. The 16-segment model was used, so divide 16 by 8; the WMSI index is 2, i.e., abnormal.</p>
        <p>In a study of 3,121 patients<sup><xref ref-type="bibr" rid="B202">202</xref></sup> divided into three risk groups according to WMSI and followed for 3 years, a WMSI of 1 (low risk) was associated with an event rate of 0.8% per year, a WMSI of 1.1-1.7 (intermediate risk) with an event rate of 2.6% per year, and a WMSI &gt; 1.7 (high risk) with an event rate of 5.5% per year.</p>
        <p>Another study with 1,560 patients sought to correlate peak WMSI with LV ejection fraction.<sup><xref ref-type="bibr" rid="B353">353</xref></sup> Patients were divided into three groups with a 3-year follow-up period. Event rates were 0.7% per year in the low-risk group, 2.0% per year in the intermediate-risk group, and 4.4% per year in the high-risk group. The events of interest were myocardial infarction, death, or other cardiovascular complications.</p>
        <p>In another study, 2,575 individuals with a negative SE at peak stress<sup><xref ref-type="bibr" rid="B354">354</xref></sup> were classified into two groups: those without RWMAs at rest or during maximal exercise and those with pre-existing RWMAs (due to infarction) which did not worsen during exercise. The latter all had CAD; the criterion for abnormality was the development of a new &#8805; 50% coronary lesion within 1 year of examination. All-cause mortality in those with negative results at 1 year was 1.1%, whereas in those with preexisting CAD it was 3.1%. Predictors of new coronary lesions within 1 year were male sex, diabetes, previous CAD, and nonischemic but abnormal stress echocardiography. These patients should be monitored due to their increased risk of morbidity and mortality, even if the latest SE is negative.</p>
        <p>In a study of 609 patients with LBBB<sup><xref ref-type="bibr" rid="B355">355</xref></sup> who underwent ESE with a follow-up period of almost 5 years, the WMSI was obtained at rest and after exercise. The difference (&#916;) in WMSI between the two time points was 29%. The mortality rate was 25% for patients with ischemia and 13% for those without ischemia.</p>
        <p>Major adverse cardiac events occurred in 18% vs. 10%, with &#916;WMSI considered an independent predictor.</p>
        <p>SE has greater value than other clinical parameters.</p>
        <p>The main causes of test cessation are onset or worsening of RWMAs, angina, ischemic ECG changes, significant arrhythmias, significant hypertension or hypotension, limiting dyspnea or fatigue, and severe tremor. Test cessation for any of these reasons or because the end of the protocol was achieved without attaining the target HR or any RWMA endpoints must be noted in the report.</p>
        <p>Echo stress guidelines discussing the risks and future prognosis of this method were recently published elsewhere.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup></p>
      </sec>
      <sec>
        <title>33. Novel Applications of Stress Echocardiography: After Radiation Therapy to the Chest and in Vasospasm</title>
        <p>Radiation therapy (RT) is one of the cornerstones of cancer treatment. High-dose irradiation of the chest is commonly used in the treatment of lung, esophageal, and breast cancers and lymphomas. Due to its anatomical proximity to these structures, the heart invariably receives doses of radiation high enough to induce cardiotoxicity. Studies show that RT accelerates the progression of coronary atherosclerosis, valvular calcification, and pulmonary and pericardial fibrosis.</p>
        <p>RT-related cardiovascular toxicity is progressive, typically developing 5 to 10 years after initial treatment, and can cause CAD and HF at an incidence up to six times higher than in the general population. The latency period between RT and onset of CAD ranges from a few years to several decades, depending on pre-treatment CV risk, patient age, cumulative radiation dose, and additional treatments, such as chemotherapy.<sup><xref ref-type="bibr" rid="B356">356</xref></sup> A thorough assessment of CV risk, including widely available risk scores and evaluation for preexisting cardiac abnormalities, is imperative in these patients.</p>
        <p>Considering that patients undergoing RT commonly receive a large cumulative radiation load, the use of imaging methods that do not expose them to extra doses is a priority.<sup><xref ref-type="bibr" rid="B357">357</xref>,<xref ref-type="bibr" rid="B358">358</xref></sup></p>
        <p>Stress echocardiography to search for changes in regional wall motion and left ventricular function has been the most widely used post-thoracic RT protocol in the last 40 years.</p>
        <p>In a recently published article, a study group led by Dr. Eugenio Picano suggested an expanded ABCDE protocol, including steps F, G, P, and R, to face the complexity of the multifaceted damage caused by radiation exposure. This expanded protocol included assessment of the mitral valve, its progressive calcification, and the repercussions of this damage under stress (step F); assessment of the progression of aortic valve calcification and transaortic gradients (step G); testing for pulmonary vascular resistance (step P); and alterations in right ventricular function (step R).<sup><xref ref-type="bibr" rid="B359">359</xref></sup></p>
        <p>Additional information may be relevant and its collection should be encouraged whenever possible. A thorough pre-examination assessment and a targeted stress test, with priority given to addressing the diagnostic hypothesis and based on sound clinical judgment, appears to be the most appropriate approach.</p>
        <p>Coronary vasospasm is one of the leading causes of dynamic stenosis of the coronary arteries, with the potential to trigger angina, unstable angina, acute myocardial infarction, syncope, and sudden death. Its diagnosis remains a major clinical challenge. Invasive provocative testing with ergonovine has been reported in several studies, but with some reservations, as mentioned in previous sections. Invasive testing exposes the patient to radiation and potentially nephrotoxic doses of contrast agents; furthermore, ergonovine is not commercially available in several countries. Noninvasive protocols using ergonovine, adenosine, or dobutamine have been described.<sup><xref ref-type="bibr" rid="B360">360</xref></sup> However, the most promising protocol has been a combination of hyperventilation (5 minutes at a respiratory rate of 25 breaths per minute) and bicycle exercise (workload increasing in 25W increments every 2-3 minutes). These two steps can clarify whether angina is due to vasospasm leading to RWMA (step A) or to coronary microvascular dysfunction (step D). Large-scale validation studies and efficacy and safety testing of this protocol are still needed. Additional data should be published after completion of the Stress Echo 2030 trial.<sup><xref ref-type="bibr" rid="B261">261</xref></sup></p>
      </sec>
      <sec>
        <title>34. Stress Echocardiography with the ABCDE Protocol</title>
        <p>Cardiac functional stress imaging is based on the detection of RWMA using two-dimensional echocardiography and is incorporated into clinical guidelines. However, it underutilizes the unique versatility of the technique, which is ideal for describing different functional abnormalities that may underlie the same regional wall movement response during stress. The ABCDE protocol, devised by Dr. Eugenio Picano in Italy for the Stress Echo 2020 multicenter study and, subsequently, the Stress Echo 2030 study, aims to expand the use of stress echocardiography to a range of applications in which it can add relevant information<sup><xref ref-type="bibr" rid="B261">261</xref></sup> (<xref ref-type="fig" rid="f73">Figure 34.1</xref>).</p>
        <fig id="f73">
          <label>Figure 34.1</label>
          <caption>
            <title>The "heart" of the Stress Echo 2030 ABCDE protocol.<sup><xref ref-type="bibr" rid="B261">261</xref></sup></title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>Five parameters converge conceptually and methodologically in the ABCDE protocol to assess multiple vulnerabilities of the ischemic patient.<sup><xref ref-type="bibr" rid="B261">261</xref></sup></p>
        <p>The five steps of the ABCDE protocol are: 1) Step A: regional wall motion/thickening (already widely used); 2) Step B: pulmonary ultrasound for B-lines to assess extravascular pulmonary congestion; 3) Step C: left ventricular contractile reserve by two-dimensional volumetric echocardiography; 4) Step D: coronary flow velocity reserve in the mid-distal left anterior descending coronary artery with pulsed Doppler; and 5) Step E: assessment of heart rate by single-lead ECG.</p>
        <p>The ABCDE stress echocardiogram provides information on the so-called five functional reserves: epicardial flow (A); diastolic reserve/congestion (B); contractile reserve (C); coronary microcirculation (D); and chronotropic reserve (E) (<xref ref-type="fig" rid="f74">Figure 34.2</xref>).</p>
        <fig id="f74">
          <label>Figure 34.2</label>
          <caption>
            <title>Integration of four main stress echo images. The four pathophysiological objectives are: assessment of epicardial stenosis (A = asynergy), pulmonary congestion (B = B lines), left ventricular myocardial function (C = contractile reserve), and coronary microvascular function (D = Doppler RVFC), E = chronotropic reserve, which can be additionally assessed.<sup><xref ref-type="bibr" rid="B261">261</xref></sup> WMSI: Wall Motion Score Index; LVCR: Left Ventricular Contractile Reserve; CFVR: Coronary Flow Velocity Reserve; HR: Heart Rate.</title>
          </caption>
          <graphic xlink:href=""/>
        </fig>
        <p>The new format is more comprehensive and allows for better functional characterization, risk stratification, and personalized adaptation of prescribed therapies.</p>
        <p>The ABCDE protocol<sup><xref ref-type="bibr" rid="B261">261</xref></sup> It is a functional test suitable for all types of stress and all patients, and extends beyond CAD. It addresses the need for sustainability in healthcare, as it requires only universally available technology and is low-cost, radiation-free, and virtually harmless.</p>
        <sec>
          <title>34.1. The ABCDE Protocol</title>
          <list list-type="bullet">
            <list-item>
              <p>
                <bold>A for Asynergy:</bold>
              </p>
              <p>This is based on the presumptive stress-induced myocardial contractility alteration in the presence of flow-limiting coronary stenosis. The oxygen supply-demand imbalance leads to a reduction in myocardial radial thickening, a parameter sometimes limited by its semi-quantitative and subjective nature. Operator dependence can be minimized (but not eliminated) by specialized training and the adoption of measures such as accreditation and quality control of echocardiography laboratories.</p>
              <p>Assessment of regional wall motion indicates that the greater the number of affected segments (universally defined), the worse the prognosis. This parameter is centered on coronary artery disease.</p>
            </list-item>
            <list-item>
              <p>
                <bold>B for B-Lines:</bold>
              </p>
              <p>Increased left atrial pressure forms the basis for a myriad of conditions. Its pathophysiological consequence concerns fluid outflow into the pulmonary pericapillary interstitium as a hydrostatic substrate. In its acute form, this fluid can be detected by ultrasound in the form of echo lines that reverberate it. During physical SE, the induction of physiological processes that potentially cause the homeostasis threshold imposed by the disease to be exceeded is a parameter that has significant prognostic value.<sup><xref ref-type="bibr" rid="B361">361</xref></sup></p>
            </list-item>
            <list-item>
              <p>
                <bold>C for Contractility:</bold>
              </p>
              <p>Contractility is the inherent ability of the myocardium to contract regardless of changes in preload or afterload.</p>
              <p>During SE, the left ventricular end-systolic volume (ESV) progressively decreases, resulting in higher arterial pressure peaks and increased load. The ratio between systolic blood pressure (SBP) and ESV predicts the left ventricular emptying capacity.<sup><xref ref-type="bibr" rid="B362">362</xref></sup></p>
              <p>Left ventricular elastance measures the contractile reserve by comparing LV performance at rest and under stress conditions. This metric can be obtained by dividing the SBP/ESV ratio during stress by the ratio at rest.</p>
              <p>Validated values are available for physical and dobutamine stress (both are &gt; 2.0). When using vasodilators, a ratio &gt; 1.1 indicates appropriate contractility.</p>
            </list-item>
            <list-item>
              <p>
                <bold>D for Coronary Artery Doppler:</bold>
              </p>
              <p>Coronary flow can be affected by epicardial conditions, such as stenosis, and myocardial dysfunction.</p>
              <p>In the first scenario, at a given flow measurement point, a limitation may occur due to compromised blood flow downstream of the obstruction under stress situations.</p>
              <p>In the second, several conditions may act to prevent adequate blood flow, such as perivascular hypertrophy, endothelial injury, dysfunction caused by inflammation, and atherosclerosis.</p>
              <p>Coronary flow reserve on echocardiography is measured by Doppler analysis of the velocity ratio in the medial or distal portion of the left anterior descending artery under stress and resting conditions. Normal values in any SE modality are &gt; 2.0.</p>
            </list-item>
            <list-item>
              <p>
                <bold>E for Electrocardiogram:</bold>
              </p>
              <p>Heart rate variability in response to stress can provide information about the autonomic function of the cardiac conduction system, serving as a marker of such function during the examination. This parameter, heart rate reserve, is obtained by dividing the maximum heart rate achieved by the resting heart rate.</p>
              <p>It is classified as positive if the ratio is &lt; 1.80 for physical or dobutamine stress and &lt; 1.22 when vasodilators are used.</p>
              <p>Beta blockers reduce heart rate under both rest and stress conditions, but have no impact on this ratio for prognostic purposes.<sup><xref ref-type="bibr" rid="B361">361</xref></sup></p>
            </list-item>
          </list>
          <p>When added to conventional SE, the ABCDE protocol results in a broader spectrum of variables being evaluated. Together, they allow for better risk stratification and help define more accurate diagnoses.</p>
          <p>Patients with microvascular disease and diastolic dysfunction sometimes have atypical presentations and may benefit from this new protocol, as it expands the diagnostic power of traditional SE.<sup><xref ref-type="bibr" rid="B363">363</xref></sup></p>
          <p>The ABCDE protocol proposes that the well-established tool of stress echocardiography be used to its fullest extent, in a simplified manner, to provide a vast range of information.</p>
        </sec>
      </sec>
      <sec>
        <title>35. Recommendations for the Management of Stress Echocardiography</title>
        <table-wrap id="t58">
          <caption>
            <title>STRESS ECHOCARDIOGRAPHY IN KNOWN OR SUSPECTED CHRONIC ISCHEMIC HEART DISEASE</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 style="background-color:#76B4CF">
                <th align="left" valign="middle">Recommendations</th>
                <th align="center" valign="middle">Strength of Recommendation</th>
                <th align="center" valign="middle">Certainty of Evidence</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle">For the diagnosis of chronic ischemic heart disease in patients with an intermediate pre-test probability.<break/> In the presence of angina symptoms in patients with prior stent implantation or coronary revascularization.<break/> In cases of moderate coronary obstruction on coronary CT angiography or invasive coronary angiography: assessment of functional significance.<break/> For post&#8211;myocardial infarction risk stratification. <break/>For the investigation of dyspnea (angina equivalent).</td>
                <td align="center" valign="middle" style="background-color:#00CC66">
                  <bold>STRONG</bold>
                </td>
                <td align="center" valign="middle" style="background-color:#00B0F0">
                  <bold>HIGH</bold>
                </td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <table-wrap id="t59">
          <caption>
            <title>STRESS ECHOCARDIOGRAPHY IN THE EMERGENCY SETTING: ACUTE CHEST PAIN</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 style="background-color:#76B4CF">
                <th align="left" valign="middle">Recomenda&#231;&#245;es</th>
                <th align="center" valign="middle">Strength of Recommendation</th>
                <th align="center" valign="middle">Certainty of Evidence</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle">In acute chest pain in patients at intermediate risk (without ECG abnormalities and/or with negative biomarkers).<break/> In patients with suspected anginal chest pain and negative or mildly elevated troponin, for patient risk stratification, provided there are no electrocardiographic changes or recurrence of pain.</td>
                <td align="center" valign="middle" style="background-color:#00CC66">
                  <bold>STRONG</bold>
                </td>
                <td align="center" valign="middle" style="background-color:#9CC2E5">
                  <bold>MODERATE</bold>
                </td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <table-wrap id="t60">
          <caption>
            <title>STRESS ECHOCARDIOGRAPHY IN VALVULAR HEART DISEASE</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 style="background-color:#76B4CF">
                <th align="left" valign="middle">Recomenda&#231;&#245;es</th>
                <th align="center" valign="middle">Strength of Recommendation</th>
                <th align="center" valign="middle">Certainty of Evidence</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle">Low-dose dobutamine stress echocardiography in patients with low-flow, low-gradient (classical) aortic valve stenosis with LVEF &lt; 50%, to confirm stenosis severity.<break/> Exercise stress echocardiography may be used to assess the hemodynamic impact of the valvular lesion in patients with discrepancy between symptoms and resting echocardiographic findings.</td>
                <td align="center" valign="middle" style="background-color:#00CC66">
                  <bold>STRONG</bold>
                </td>
                <td align="center" valign="middle" style="background-color:#00B0F0">
                  <bold>HIGH</bold>
                </td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <table-wrap id="t61">
          <caption>
            <title>DIASTOLIC STRESS ECHOCARDIOGRAPHY</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 style="background-color:#76B4CF">
                <th align="left" valign="middle">Recommendations</th>
                <th align="center" valign="middle">Strength of Recommendation</th>
                <th align="center" valign="middle">Certainty of Evidence</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle">Exercise stress echocardiography, preferably using a supine cycle ergometer or treadmill, in patients with unexplained dyspnea and: &#8211; Grade 1 diastolic dysfunction; &#8211; Intermediate H<sub>2</sub>FPEF or HFA-PEFF scores (2&#8211;5 points and 2&#8211;4 points, respectively).</td>
                <td align="center" valign="middle" style="background-color:#00CC66">
                  <bold>STRONG</bold>
                </td>
                <td align="center" valign="middle" style="background-color:#00B0F0">
                  <bold>HIGH</bold>
                </td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <table-wrap id="t62">
          <caption>
            <title>STRESS ECHOCARDIOGRAPHY WITH ULTRASOUND ENHANCING AGENTS (UEAs) FOR ENDOCARDIAL BORDER DEFINITION</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 style="background-color:#76B4CF">
                <th align="left" valign="middle">Recommendations</th>
                <th align="center" valign="middle">Strength of Recommendation</th>
                <th align="center" valign="middle">Certainty of Evidence</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle">Stress echocardiography with UEAs when two or more contiguous myocardial segments are not visualized (in the apical view), to improve diagnostic accuracy.</td>
                <td align="center" valign="middle" style="background-color:#00CC66">
                  <bold>STRONG</bold>
                </td>
                <td align="center" valign="middle" style="background-color:#00B0F0">
                  <bold>HIGH</bold>
                </td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <table-wrap id="t63">
          <caption>
            <title>STRESS ECHOCARDIOGRAPHY WITH ULTRASOUND ENHANCING AGENTS (UEAs) FOR MYOCARDIAL PERFUSION ANALYSIS</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 style="background-color:#76B4CF">
                <th align="left" valign="middle">Recomenda&#231;&#245;es</th>
                <th align="center" valign="middle">Strength of Recommendation</th>
                <th align="center" valign="middle">Certainty of Evidence</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle">Myocardial perfusion assessment to increase accuracy in identifying obstructive coronary artery disease and for the evaluation of myocardial viability.</td>
                <td align="center" valign="middle" style="background-color:#FFFF99">
                  <bold>WEAK</bold>
                </td>
                <td align="center" valign="middle" style="background-color:#00B0F0">
                  <bold>HIGH</bold>
                </td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <table-wrap id="t64">
          <caption>
            <title>ECO ESTRESSE EM PEDIATRIA</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 style="background-color:#76B4CF">
                <th align="left" valign="middle"/>
                <th align="center" valign="middle">Strength of Recommendation</th>
                <th align="center" valign="middle">Certainty of Evidence</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle">Appears to be advantageous for the assessment of valvular stenosis or regurgitation and dynamic obstruction of the left or right ventricular outflow tracts.<break/> Pulmonary arterial hypertension.<break/> Assessment of myocardial ischemia (AAOCA, ALCAPA, Kawasaki disease, and in patients undergoing cardiac surgery with coronary manipulation, such as after the Jatene procedure).<break/> Post-heart transplantation for ischemia assessment</td>
                <td align="center" valign="middle" style="background-color:#FFFF99">
                  <bold>WEAK</bold>
                </td>
                <td align="center" valign="middle" style="background-color:#DEEAF6">
                  <bold>LOW</bold>
                </td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN24">
              <p>AAOCA: Anomalous aortic origin of the coronary arteries; ALCAPA: Anomalous origin of the left coronary artery from the pulmonary artery.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
    </body>
    <back>
      <glossary>
        <def-list>
          <title>List of abbreviations and acronyms</title>
          <def-item>
            <term id="G61">ACS</term>
            <def>
              <p>Acute coronary syndrome</p>
            </def>
          </def-item>
          <def-item>
            <term id="G62">AF</term>
            <def>
              <p>Atrial fibrillation</p>
            </def>
          </def-item>
          <def-item>
            <term id="G63">AS</term>
            <def>
              <p>Aortic stenosis</p>
            </def>
          </def-item>
          <def-item>
            <term id="G64">AV</term>
            <def>
              <p>Atrioventricular</p>
            </def>
          </def-item>
          <def-item>
            <term id="G65">AVA</term>
            <def>
              <p>Aortic valve area</p>
            </def>
          </def-item>
          <def-item>
            <term id="G66">BP</term>
            <def>
              <p>Blood pressure</p>
            </def>
          </def-item>
          <def-item>
            <term id="G67">CAD</term>
            <def>
              <p>Coronary artery disease</p>
            </def>
          </def-item>
          <def-item>
            <term id="G68">CAV</term>
            <def>
              <p>Cardiac allograft vasculopathy</p>
            </def>
          </def-item>
          <def-item>
            <term id="G69">CCDC</term>
            <def>
              <p>Chronic Chagas disease cardiomyopathy</p>
            </def>
          </def-item>
          <def-item>
            <term id="G70">CFR</term>
            <def>
              <p>Coronary flow reserve</p>
            </def>
          </def-item>
          <def-item>
            <term id="G71">CMR</term>
            <def>
              <p>Cardiac magnetic resonance</p>
            </def>
          </def-item>
          <def-item>
            <term id="G72">CO</term>
            <def>
              <p>Cardiac output</p>
            </def>
          </def-item>
          <def-item>
            <term id="G73">CR</term>
            <def>
              <p>Contractile reserve</p>
            </def>
          </def-item>
          <def-item>
            <term id="G74">CT</term>
            <def>
              <p>Computed tomography</p>
            </def>
          </def-item>
          <def-item>
            <term id="G75">CVD</term>
            <def>
              <p>Cardiovascular disease</p>
            </def>
          </def-item>
          <def-item>
            <term id="G76">DBP</term>
            <def>
              <p>Diastolic blood pressure</p>
            </def>
          </def-item>
          <def-item>
            <term id="G77">DCM</term>
            <def>
              <p>Dilated cardiomyopathy</p>
            </def>
          </def-item>
          <def-item>
            <term id="G78">DF</term>
            <def>
              <p>Diastolic function</p>
            </def>
          </def-item>
          <def-item>
            <term id="G79">DSE</term>
            <def>
              <p>Dobutamine stress echocardiography</p>
            </def>
          </def-item>
          <def-item>
            <term id="G80">ECG</term>
            <def>
              <p>Electrocardiogram</p>
            </def>
          </def-item>
          <def-item>
            <term id="G81">ED</term>
            <def>
              <p>Emergency department</p>
            </def>
          </def-item>
          <def-item>
            <term id="G82">ESE</term>
            <def>
              <p>Exercise stress echocardiography</p>
            </def>
          </def-item>
          <def-item>
            <term id="G83">FAC</term>
            <def>
              <p>Fractional area change</p>
            </def>
          </def-item>
          <def-item>
            <term id="G84">GLS</term>
            <def>
              <p>Global longitudinal strain</p>
            </def>
          </def-item>
          <def-item>
            <term id="G85">GPCR</term>
            <def>
              <p>G protein-coupled receptor</p>
            </def>
          </def-item>
          <def-item>
            <term id="G86">HCM</term>
            <def>
              <p>Hypertrophic cardiomyopathy</p>
            </def>
          </def-item>
          <def-item>
            <term id="G87">HFpEF</term>
            <def>
              <p>Heart failure with preserved ejection fraction</p>
            </def>
          </def-item>
          <def-item>
            <term id="G88">HR</term>
            <def>
              <p>Heart rate</p>
            </def>
          </def-item>
          <def-item>
            <term id="G89">LAD</term>
            <def>
              <p>Left anterior descending artery</p>
            </def>
          </def-item>
          <def-item>
            <term id="G90">LBBB</term>
            <def>
              <p>Left bundle branch block</p>
            </def>
          </def-item>
          <def-item>
            <term id="G91">LFLG</term>
            <def>
              <p>Low flow-low gradient</p>
            </def>
          </def-item>
          <def-item>
            <term id="G92">LMCA</term>
            <def>
              <p>Left main coronary artery</p>
            </def>
          </def-item>
          <def-item>
            <term id="G93">LV</term>
            <def>
              <p>Left ventricle</p>
            </def>
          </def-item>
          <def-item>
            <term id="G94">LVEF</term>
            <def>
              <p>Left ventricular ejection fraction</p>
            </def>
          </def-item>
          <def-item>
            <term id="G95">LVFP</term>
            <def>
              <p>Left ventricular filling pressure</p>
            </def>
          </def-item>
          <def-item>
            <term id="G96">LVOT</term>
            <def>
              <p>Left ventricular outflow tract</p>
            </def>
          </def-item>
          <def-item>
            <term id="G97">LVOTO</term>
            <def>
              <p>Left ventricular outflow tract obstruction</p>
            </def>
          </def-item>
          <def-item>
            <term id="G98">MI</term>
            <def>
              <p>Mechanical index</p>
            </def>
          </def-item>
          <def-item>
            <term id="G99">MINOCA</term>
            <def>
              <p>Myocardial infarction with nonobstructive coronary arteries</p>
            </def>
          </def-item>
          <def-item>
            <term id="G100">MP</term>
            <def>
              <p>Myocardial perfusion</p>
            </def>
          </def-item>
          <def-item>
            <term id="G101">MR</term>
            <def>
              <p>Myocardial reserve</p>
            </def>
          </def-item>
          <def-item>
            <term id="G102">MS</term>
            <def>
              <p>Mitral stenosis</p>
            </def>
          </def-item>
          <def-item>
            <term id="G103">MVD</term>
            <def>
              <p>Mitral valve disease</p>
            </def>
          </def-item>
          <def-item>
            <term id="G104">NIDCM</term>
            <def>
              <p>Nonischemic dilated cardiomyopathy</p>
            </def>
          </def-item>
          <def-item>
            <term id="G105">PAH</term>
            <def>
              <p>Pulmonary hypertension</p>
            </def>
          </def-item>
          <def-item>
            <term id="G106">PAP</term>
            <def>
              <p>Pulmonary artery pressure</p>
            </def>
          </def-item>
          <def-item>
            <term id="G107">PASE</term>
            <def>
              <p>Pacing stress echocardiography</p>
            </def>
          </def-item>
          <def-item>
            <term id="G108">PASP</term>
            <def>
              <p>Pulmonary artery systolic pressure</p>
            </def>
          </def-item>
          <def-item>
            <term id="G109">PDA</term>
            <def>
              <p>Posterior descending artery</p>
            </def>
          </def-item>
          <def-item>
            <term id="G110">PEG</term>
            <def>
              <p>Polyethylene glycol</p>
            </def>
          </def-item>
          <def-item>
            <term id="G111">PET</term>
            <def>
              <p>Positron emission tomography</p>
            </def>
          </def-item>
          <def-item>
            <term id="G112">PPM</term>
            <def>
              <p>Permanent pacemaker</p>
            </def>
          </def-item>
          <def-item>
            <term id="G113">RBBB</term>
            <def>
              <p>Right bundle branch block</p>
            </def>
          </def-item>
          <def-item>
            <term id="G114">RHC</term>
            <def>
              <p>Right heart catheterization</p>
            </def>
          </def-item>
          <def-item>
            <term id="G115">RLS</term>
            <def>
              <p>Regional longitudinal strain</p>
            </def>
          </def-item>
          <def-item>
            <term id="G116">RT</term>
            <def>
              <p>Radiation therapy</p>
            </def>
          </def-item>
          <def-item>
            <term id="G117">RV</term>
            <def>
              <p>Right ventricle</p>
            </def>
          </def-item>
          <def-item>
            <term id="G118">RWMA</term>
            <def>
              <p>Regional wall motion abnormality</p>
            </def>
          </def-item>
          <def-item>
            <term id="G119">SAM</term>
            <def>
              <p>Systolic anterior motion</p>
            </def>
          </def-item>
          <def-item>
            <term id="G120">SBP</term>
            <def>
              <p>Systolic blood pressure</p>
            </def>
          </def-item>
          <def-item>
            <term id="G121">SE</term>
            <def>
              <p>Stress echocardiography</p>
            </def>
          </def-item>
          <def-item>
            <term id="G122">SPECT</term>
            <def>
              <p>Single-photon emission computed tomography</p>
            </def>
          </def-item>
          <def-item>
            <term id="G123">SR</term>
            <def>
              <p>Strain rate</p>
            </def>
          </def-item>
          <def-item>
            <term id="G124">TAPSE</term>
            <def>
              <p>Tricuspid annular plane systolic excursion</p>
            </def>
          </def-item>
          <def-item>
            <term id="G125">TRV</term>
            <def>
              <p>Tricuspid regurgitation velocity</p>
            </def>
          </def-item>
          <def-item>
            <term id="G126">TTE</term>
            <def>
              <p>Transthoracic echocardiography</p>
            </def>
          </def-item>
          <def-item>
            <term id="G127">UEA</term>
            <def>
              <p>Ultrasound enhancing agent</p>
            </def>
          </def-item>
          <def-item>
            <term id="G128">WMSI</term>
            <def>
              <p>Wall motion score index</p>
            </def>
          </def-item>
        </def-list>
      </glossary>
      <fn-group>
        <fn fn-type="other" id="fn4">
          <label>Development:</label>
          <p>Department of Cardiovascular Imaging of the Brazilian Society of Cardiology, Inter-American Society of Cardiovascular Imaging (In Portuguese: Departamento de Imagem Cardiovascular da Sociedade Brasileira de Cardiologia &#8211; DIC/SBC, Sociedade Interamericana de Imagem Cardiovascular &#8211; SISIAC)</p>
        </fn>
        <fn fn-type="other" id="fn5">
          <label>SBC Clinical Practice Guidelines Committee:</label>
          <p>Humberto Graner Moreira (Coordinator), F&#233;lix Jos&#233; Alvarez Ramires, Helena Cramer Veiga Rey, Jos&#233; Augusto Soares Barreto Filho, Nadine Oliveira Clausell.</p>
        </fn>
        <fn fn-type="other" id="fn6">
          <label>Note:</label>
          <p>These guidelines are for information purposes and should not replace the clinical judgment of a physician, who must ultimately determine the appropriate treatment for each patient.</p>
        </fn>
      </fn-group>
      <sec sec-type="data-availability" specific-use="data-in-article">
        <title>Data Availability:</title>
        <p>The data underlying the text of the Position Statement are included in the manuscript.</p>
      </sec>
    </back>
  </sub-article>
</article>
