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<article xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" dtd-version="3.0" article-type="research-article" xml:lang="pt">
  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq. Bras. Cardiol.</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</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">HbgnrLNxPYNWdGVvQqWHwxN</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2014000100011</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S0066-782X2013005000110</article-id>
      <article-id pub-id-type="other">0011</article-id>
      <article-id pub-id-type="publisher-id">S0066-782X2013005000110</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20130228</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="pt">Desfecho de Curto e Longo Prazo na Cardiomiopatia Induzida
               por Estresse: O que Podemos Esperar?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Ribeiro</surname>
            <given-names>V&#226;nia Filipa Andrade</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
          <xref ref-type="corresp" rid="c01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Vasconcelos</surname>
            <given-names>Mariana</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mel&#227;o</surname>
            <given-names>Filipa</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ferreira</surname>
            <given-names>Ester</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Malangatana</surname>
            <given-names>Gracieta</given-names>
          </name>
          <xref ref-type="aff" rid="aff02">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Maciel</surname>
            <given-names>Maria J&#250;lia</given-names>
          </name>
          <xref ref-type="aff" rid="aff02">2</xref>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <label>1</label>
        <institution content-type="orgname">Centro Hospitalar S&#227;o Jo&#227;o</institution>
        <addr-line>
          <named-content content-type="city">Porto</named-content>
        </addr-line>
        <country>Portugal</country>
        <institution content-type="original">Centro Hospitalar S&#227;o Jo&#227;o, Porto -
               Portugal</institution>
      </aff>
      <aff id="aff02">
        <label>2</label>
        <institution content-type="orgname">Hospital Pedro Hispano</institution>
        <addr-line>
          <named-content content-type="city">Porto</named-content>
        </addr-line>
        <country>Portugal</country>
        <institution content-type="original">Hospital Pedro Hispano, Porto -
               Portugal</institution>
      </aff>
      <author-notes>
        <corresp id="c01"><bold>Correspond&#234;ncia: V&#226;nia Filipa Andrade Ribeiro</bold>, Alameda Professor Hern&#226;ni
               Monteiro, CEP 4200-319, Porto - Portugal. E-mail:
                  <email>ribeiro_vania@hotmail.com</email>
            </corresp>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial Conflito de Interesses</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="collection">
        <month>1</month>
        <year>2014</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>26</day>
        <month>11</month>
        <year>2013</year>
      </pub-date>
      <volume>102</volume>
      <issue>1</issue>
      <fpage>80</fpage>
      <lpage>85</lpage>
      <history>
        <date date-type="received">
          <day>13</day>
          <month>05</month>
          <year>2013</year>
        </date>
        <date date-type="rev-recd">
          <day>24</day>
          <month>06</month>
          <year>2013</year>
        </date>
        <date date-type="accepted">
          <day>23</day>
          <month>07</month>
          <year>2013</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">
          <license-p>This is an Open Access article distributed under the terms of the Creative
                  Commons Attribution Non-Commercial License which permits unrestricted
                  non-commercial use, distribution, and reproduction in any medium, provided the
                  original work is properly cited. </license-p>
        </license>
      </permissions>
      <abstract xml:lang="pt">
        <sec>
          <title>Fundamento:</title>
          <p>A cardiomiopatia de estresse/Takotsubo (CT) &#233; uma entidade diagn&#243;stica cada vez
                  mais reconhecida.</p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p>Este estudo teve como objetivo avaliar a preval&#234;ncia e os preditores cl&#237;nicos de
                  complica&#231;&#245;es de curto e longo prazo de pacientes (pts) com CT.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>Foram inclu&#237;dos todos os pts consecutivamente admitidos no nosso centro, entre
                  novembro de 2006 e agosto de 2011, que preenchiam os crit&#233;rios diagn&#243;sticos da
                  Cl&#237;nica Mayo.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>Analisaram-se 37 pts (35 mulheres), com idade m&#233;dia de 63 &#177; 13 anos. A CT foi
                  precipitada na maioria dos casos por eventos de estresse emocional (57%) e dor
                  tor&#225;cica foi o sintoma de apresenta&#231;&#227;o mais frequente (89%). O electrocardiograma
                  na admiss&#227;o mostrou supradesnivelamento do segmento ST em 12 pts (32%) e invers&#227;o
                  da onda T em 15 casos (41%). Verificou-se disfun&#231;&#227;o sist&#243;lica ventricular esquerda
                  (VE) grave em 16 pts (45%) e a eleva&#231;&#227;o m&#233;dia de troponina I foi de 2,6 &#177; 1,8
                  ng/mL. A taxa de complica&#231;&#245;es intra-hospitalares foi de 30%, sendo o choque
                  cardiog&#234;nico a situa&#231;&#227;o mais comum. O estresse f&#237;sico, a disfun&#231;&#227;o sist&#243;lica grave
                  do VE e o valor de pico do pept&#237;deo natriur&#233;tico cerebral (BNP) foram preditores
                  de complica&#231;&#245;es agudas. N&#227;o foi encontrada associa&#231;&#227;o entre o pico de troponina I
                  e a apresenta&#231;&#227;o eletrocardiogr&#225;fica. Trinta e cinco pacientes foram acompanhados
                  por um tempo m&#233;dio de 482 &#177; 512 dias, sem recorr&#234;ncia cl&#237;nica.</p>
        </sec>
        <sec>
          <title>Conclus&#227;o:</title>
          <p>Na nossa s&#233;rie de pacientes, a CT foi associada a uma alta taxa de complica&#231;&#245;es
                  intra-hospitalares. O estresse f&#237;sico, a disfun&#231;&#227;o sist&#243;lica do VE e o valor de
                  pico do BNP foram preditores de desfechos adversos agudos.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <kwd>Cardiomiopatia de Takotsubo</kwd>
        <kwd>Estresse psicol&#243;gico</kwd>
      </kwd-group>
      <counts>
        <fig-count count="2"/>
        <table-count count="3"/>
        <equation-count count="0"/>
        <ref-count count="19"/>
        <page-count count="6"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>A cardiomiopatia de estresse/Takotsubo (CT) &#233; uma s&#237;ndrome cada vez mais relatada,
            caracterizada por disfun&#231;&#227;o sist&#243;lica transit&#243;ria na aus&#234;ncia de doen&#231;ca coron&#225;ria
            obstrutiva, a qual imita o infarto do mioc&#225;rdio.</p>
      <p>A exata incid&#234;ncia de CT &#233; desconhecida, mas estudos recentes revelaram uma preval&#234;ncia
            de aproximadamente 2% de pacientes com s&#237;ndrome coronariana aguda nos Estados Unidos e
               Europa<xref ref-type="bibr" rid="B01">1</xref>.</p>
      <p>Um estressor emocional ou f&#237;sico frequentemente precede o desenvolvimento de sintomas,
            mas a fisiopatologia da CT &#233; incerta. V&#225;rias hip&#243;teses t&#234;m sido propostas, incluindo a
            cardiotoxicidade mediada por catecolaminas, espasmo da circula&#231;&#227;o coron&#225;ria
            microvascular e disfun&#231;&#227;o das c&#233;lulas endoteliais<xref ref-type="bibr" rid="B02">2</xref><sup>-</sup><xref ref-type="bibr" rid="B04">4</xref>.</p>
      <p>Esse estudo avalia as caracter&#237;sticas cl&#237;nicas de 37 pacientes com essa doen&#231;a,
            consecutivamente admitidos em nosso centro hospitalar terci&#225;rio, e os preditores de
            eventos adversos em curto e longo prazo nessa popula&#231;&#227;o.</p>
    </sec>
    <sec sec-type="methods">
      <title>M&#233;todos</title>
      <p>De novembro de 2006 a agosto de 2011, identificamos retrospectivamente, em nosso centro
            hospitalar terci&#225;rio, 37 pacientes com CT que tinham sido submetidos a cateterismo
            card&#237;aco esquerdo para s&#237;ndrome coronariana aguda. Todos os pacientes foram atendidos em
            nosso departamento de emerg&#234;ncia ou foram transferidos de outro hospital. Os crit&#233;rios
            de inclus&#227;o para a cardiomiopatia de Takotsubo, de acordo com a Cl&#237;nica Mayo, foram:
            anomalias transit&#243;rias de movimento da parede do VE, envolvendo os segmentos apicais
            e/ou m&#233;dio-ventriculares do mioc&#225;rdio, com as anomalias se estendendo al&#233;m de uma &#250;nica
            distribui&#231;&#227;o coron&#225;ria epic&#225;rdica; aus&#234;ncia de doen&#231;a arterial coronariana obstrutiva
            epic&#225;rdica ou evid&#234;ncia angiogr&#225;fica de ruptura aguda da placa, que pudesse ser
            respons&#225;vel pela anomalia observada do movimento de parede; novas altera&#231;&#245;es no ECG,
            como a eleva&#231;&#227;o transit&#243;ria do segmento ST e/ou invers&#227;o difusa de onda T ou eleva&#231;&#227;o da
            troponina; aus&#234;ncia de feocromocitoma ou miocardite.</p>
      <p>Os dados demogr&#225;ficos dos pacientes, apresenta&#231;&#227;o cl&#237;nica, achados eletrocardiogr&#225;ficos,
            n&#237;veis de biomarcadores card&#237;acos e complica&#231;&#245;es foram avaliados durante a
            hospitaliza&#231;&#227;o. Todos os pacientes foram submetidos a ventriculografia esquerda e
            avalia&#231;&#227;o ecocardiogr&#225;fica, na admiss&#227;o e acompanhamento. O acompanhamento cl&#237;nico foi
            realizado atrav&#233;s de visitas ambulatoriais. Uma resson&#226;ncia magn&#233;tica card&#237;aca foi
            realizada em treze pacientes. Foram registrados a recorr&#234;ncia dos sintomas,
            rehospitaliza&#231;&#227;o, estado funcional e morte.</p>
      <p>Os dados foram analisados utilizando-se o software SPSS, vers&#227;o 20.0 e a associa&#231;&#227;o
            entre as vari&#225;veis basais e as complica&#231;&#245;es agudas foi estimada atrav&#233;s do <italic>odds
               ratio</italic> - OR (raz&#227;o de chances) para as vari&#225;veis categ&#243;ricas e teste
               <italic>t</italic> pareado para as vari&#225;veis cont&#237;nuas.</p>
    </sec>
    <sec sec-type="results">
      <title>Resultados</title>
      <p>Trinta e cinco pacientes (95%) eram mulheres, com idade m&#233;dia de 63 &#177; 13 anos (<xref ref-type="table" rid="t01">Tabela 1</xref>). A maioria dos pacientes apresentava
            fatores de risco cardiovascular: vinte e sete pacientes (73%) tinham hipertens&#227;o,
            dezenove (51%) tinham dislipidemia e seis (16%) tinham diabetes. A apresenta&#231;&#227;o mais
            comum foi a dor no peito (89%), mas tr&#234;s pacientes (8%) apresentaram dispneia e um (3%)
            apresentou lipotimia. Um fator desencadeante foi identificado em vinte e nove pacientes
            (78%), dos quais o mais comum foi estresse emocional (57%). Um gatilho f&#237;sico estava
            presente em oito pacientes (22%) e incluiu um procedimento cir&#250;rgico eletivo,
            exacerba&#231;&#227;o da doen&#231;a pulmonar obstrutiva cr&#244;nica e hospitaliza&#231;&#227;o recente. O ECG de
            admiss&#227;o revelou eleva&#231;&#227;o do segmento ST em doze pacientes (32%) e invers&#227;o generalizada
            da onda T em vinte e cinco pacientes (41%) (<xref ref-type="fig" rid="f01">Figura
               1</xref>). Outros achados do ECG incluem taquicardia sinusal e novas ondas Q. Cinco
            pacientes (14%), n&#227;o apresentaram altera&#231;&#245;es no ECG. Troponina I foi positiva em todos
            os casos com um pico m&#233;dio de 2,6 &#177; 1,8 ng/mL. O valor m&#233;dio de pico do pept&#237;deo
            natriur&#233;tico cerebral (BNP) foi de 1.160 &#177; 1564 pg/mL. A avalia&#231;&#227;o do ventr&#237;culo
            esquerdo demonstrou a dilata&#231;&#227;o (<italic>balooning</italic>) apical cl&#225;ssica em trinta e
            quatro pacientes (92%) e uma variante de m&#233;dia parede foi demonstrada em tr&#234;s pacientes
            (8%) (<xref ref-type="fig" rid="f02">Figura 2</xref>). A fra&#231;&#227;o de eje&#231;&#227;o m&#233;dia pela
            ecocardiografia foi de 40%.</p>
      <table-wrap id="t01">
        <label>Tabela 1</label>
        <caption>
          <title>Caracter&#237;sticas basais da popula&#231;&#227;o estudada</title>
        </caption>
        <table frame="hsides" rules="rows">
          <thead>
            <tr>
              <th align="left">
                <bold>Caracter&#237;stica</bold>
              </th>
              <th>
                <bold>Total (n = 37) Valor</bold>
              </th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td>Idade (anos), m&#233;dia &#177; DP</td>
              <td align="center">63 &#177; 13</td>
            </tr>
            <tr>
              <td>Feminino</td>
              <td align="center">35 (95%)</td>
            </tr>
            <tr>
              <td colspan="2">
                <bold>Fatores de Risco Cardiovascular</bold>
              </td>
            </tr>
            <tr>
              <td>Diabetes mellitus</td>
              <td align="center">6 (16%)</td>
            </tr>
            <tr>
              <td>Hipertens&#227;o</td>
              <td align="center">27 (73%)</td>
            </tr>
            <tr>
              <td>Dislipidemia</td>
              <td align="center">19 (51%)</td>
            </tr>
            <tr>
              <td>Tabagismo (atual ou pr&#233;vio)</td>
              <td align="center">2 (5%)</td>
            </tr>
            <tr>
              <td colspan="2">
                <bold>Apresenta&#231;&#227;o cl&#237;nica</bold>
              </td>
            </tr>
            <tr>
              <td>Dor tor&#225;cica</td>
              <td align="center">33 (89%)</td>
            </tr>
            <tr>
              <td>Dispneia</td>
              <td align="center">3 (8%)</td>
            </tr>
            <tr>
              <td>Perda de consci&#234;ncia</td>
              <td align="center">1(3%)</td>
            </tr>
            <tr>
              <td colspan="2">
                <bold>Fator desencadeante</bold>
              </td>
            </tr>
            <tr>
              <td>Estresse emocional</td>
              <td align="center">21 (57%)</td>
            </tr>
            <tr>
              <td>Estresse f&#237;sico</td>
              <td align="center">8 (22%)</td>
            </tr>
            <tr>
              <td>Sem fator desencadeante</td>
              <td align="center">8 (22%)</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn>
            <p>DP: desvio-padr&#227;o.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <fig id="f01" fig-type="other">
        <label>Figura 1</label>
        <caption>
          <title>Padr&#245;es eletrocardiogr&#225;ficos representativos no momento da interna&#231;&#227;o, com (A)
                  eleva&#231;&#227;o do segmento ST em V2 a V6 e (B) invers&#227;o de onda T em V2 a V5, DI e
                  aVL.</title>
        </caption>
        <graphic xlink:href="1678-4170-abc-102-01-0080-30228-gf01.jpg"/></fig>
      <fig id="f02" fig-type="other">
        <label>Figura 2</label>
        <caption>
          <title>Ventriculograma esquerdo em (A), final da s&#237;stole e (B) fim da di&#225;stole,
                  mostrando uma variante de parede m&#233;dia com contra&#231;&#227;o apical.</title>
        </caption>
        <graphic xlink:href="1678-4170-abc-102-01-0080-30228-gf02.jpg"/></fig>
      <p>Complica&#231;&#245;es agudas ocorreram em onze pacientes (30%), sendo que alguns casos
            apresentaram mais de uma complica&#231;&#227;o (<xref ref-type="table" rid="t02">Tabela 2</xref>).
            O choque cardiog&#234;nico foi a situa&#231;&#227;o mais comum, mas dois pacientes desenvolveram edema
            pulmonar agudo. Dist&#250;rbios do ritmo card&#237;aco tamb&#233;m foram observados. Um paciente teve
            um epis&#243;dio de fibrila&#231;&#227;o atrial r&#225;pida, o qual foi cardiovertido com amiodarona. Um
            bloqueio AV de terceiro grau foi documentado em dois pacientes, com um deles
            necessitando de um marca-passo permanente devido &#224; persist&#234;ncia do bloqueio AV ap&#243;s a
            recupera&#231;&#227;o da fun&#231;&#227;o sist&#243;lica. A avalia&#231;&#227;o ecocardiogr&#225;fica realizada em todos os
            pacientes identificou dois casos de gradiente significativo da via de sa&#237;da do VE e dois
            casos de trombo intraventricular.</p>
      <table-wrap id="t02">
        <label>Tabela 2</label>
        <caption>
          <title>Complica&#231;&#245;es intrahospitalares na popula&#231;&#227;o estudada</title>
        </caption>
        <table frame="hsides" rules="rows">
          <thead>
            <tr>
              <th align="left">
                <bold>Complica&#231;&#227;o intrahospitalar</bold>
              </th>
              <th>
                <bold>n (%)</bold>
              </th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td>Choque Cardiog&#234;nico</td>
              <td align="center">4 (11%)</td>
            </tr>
            <tr>
              <td>Trombo intraventricular</td>
              <td align="center">2 (5%)</td>
            </tr>
            <tr>
              <td>Fibrila&#231;&#227;o atrial</td>
              <td align="center">1 (3%)</td>
            </tr>
            <tr>
              <td>Edema pulmonar</td>
              <td align="center">2 (5%)</td>
            </tr>
            <tr>
              <td>Bloqueio AV de terceiro grau</td>
              <td align="center">2 (5%)</td>
            </tr>
            <tr>
              <td>Gradiente significativo da via de sa&#237;da do ventr&#237;culo esquerdo</td>
              <td align="center">2 (5%)</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn>
            <p>AV: atriavertricular.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>N&#227;o houve mortes. A dura&#231;&#227;o m&#233;dia de perman&#234;ncia hospitalar foi de 7,9 &#177; 5,6 dias, com
            maior tempo de interna&#231;&#227;o em pacientes com complica&#231;&#245;es (12,0 &#177; 8,7 vs 6,1 &#177; 2,1, p =
            0,05), como esperado. Estresse f&#237;sico (<italic>odds ratio</italic>: 6,4; 95% intervalo
            de confian&#231;a: 1,2 a 34,6), fun&#231;&#227;o sist&#243;lica grave na admiss&#227;o (<italic>odds
               ratio</italic>: 12,2, intervalo de confian&#231;a de 95%: 2,1-71,0) e o pico de BNP
            (2.324,7 &#177; 2.107,2 vs. 512,8 &#177; 542,9, p = 0,024) foram preditores de complica&#231;&#245;es
            agudas. Por outro lado, n&#227;o foi encontrada associa&#231;&#227;o entre o pico de troponina I,
            apresenta&#231;&#227;o eletrocardiogr&#225;fica e tempo de evolu&#231;&#227;o dos sintomas (<xref ref-type="table" rid="t03">Tabela 3</xref>).</p>
      <table-wrap id="t03">
        <label>Tabela 3</label>
        <caption>
          <title>Preditores cl&#237;nicos de complica&#231;&#245;es intrahospitalares na popula&#231;&#227;o
                  estudada</title>
        </caption>
        <table frame="hsides" rules="rows">
          <thead>
            <tr>
              <th> </th>
              <th>
                <bold>Complica&#231;&#245;es Agudas (n = 11)</bold>
              </th>
              <th>
                <bold>Sem complica&#231;&#245;es agudas (n = 26)</bold>
              </th>
              <th>
                <bold>Valor p</bold>
              </th>
              <th>
                <italic>OR </italic>
                <bold>IC95%</bold>
              </th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td>Idade (anos)</td>
              <td align="center">63,2 &#177; 20,3</td>
              <td align="center">63,0 &#177; 8,9</td>
              <td align="center">0,98</td>
              <td align="center"> </td>
            </tr>
            <tr>
              <td>Fator desencadeante</td>
              <td align="center"> </td>
              <td align="center"> </td>
              <td align="center">0,03</td>
              <td align="center"> </td>
            </tr>
            <tr>
              <td>Estresse emocional</td>
              <td align="center">3 (27,3%)</td>
              <td align="center">18 (69,2%)</td>
              <td align="center"> </td>
              <td align="center"> </td>
            </tr>
            <tr>
              <td>Estresse f&#237;sico</td>
              <td align="center">5 (45,5%)</td>
              <td align="center">3 (11,5%)</td>
              <td align="center"> </td>
              <td align="center">6,4 (1,2-34,6)</td>
            </tr>
            <tr>
              <td>Sem fator desencadeante</td>
              <td align="center">3 (27,3%)</td>
              <td align="center">5 (19,2%)</td>
              <td align="center"> </td>
              <td align="center"> </td>
            </tr>
            <tr>
              <td>Tempo a partir do aparecimento dos sintomas (horas)</td>
              <td align="center">16,6 &#177; 18,5</td>
              <td align="center">9,83 &#177; 16,2</td>
              <td align="center">0,28</td>
              <td align="center"> </td>
            </tr>
            <tr>
              <td>Apresenta&#231;&#227;o do ECG</td>
              <td align="center"> </td>
              <td align="center"> </td>
              <td align="center">0,49</td>
              <td align="center"> </td>
            </tr>
            <tr>
              <td>ECG normal</td>
              <td align="center">3 (27,3%)</td>
              <td align="center">2 (7,7%)</td>
              <td align="center"> </td>
              <td align="center"> </td>
            </tr>
            <tr>
              <td>Eleva&#231;&#227;o do segmento ST</td>
              <td align="center">3 (27,3%)</td>
              <td align="center">9 (34,6%)</td>
              <td align="center"> </td>
              <td align="center"> </td>
            </tr>
            <tr>
              <td>Ondas T negativas</td>
              <td align="center">3 (27,3%)</td>
              <td align="center">12 (46,2%)</td>
              <td align="center"> </td>
              <td align="center"> </td>
            </tr>
            <tr>
              <td>Pico de troponina I (ng/mL)</td>
              <td align="center">2,5 &#177; ,8</td>
              <td align="center">2,6 &#177; 1,8</td>
              <td align="center">0,98</td>
              <td align="center"> </td>
            </tr>
            <tr>
              <td>Pico de BNP (pg/mL)</td>
              <td align="center">2324,7 &#177; 2107,2</td>
              <td align="center">512,8 &#177; 542,9</td>
              <td align="center">0,02</td>
              <td align="center"> </td>
            </tr>
            <tr>
              <td>Fra&#231;&#227;o de eje&#231;&#227;o</td>
              <td align="center"> </td>
              <td align="center"> </td>
              <td align="center">0,02</td>
              <td align="center"> </td>
            </tr>
            <tr>
              <td>&#8805; 45%-55%</td>
              <td align="center">1 (9,1%)</td>
              <td align="center">2 (7,7%)</td>
              <td align="center"> </td>
              <td align="center"> </td>
            </tr>
            <tr>
              <td>&#8805; 35%-45%</td>
              <td align="center">1 (9,1%)</td>
              <td align="center">16 (61,5%)</td>
              <td align="center"> </td>
              <td align="center"> </td>
            </tr>
            <tr>
              <td>&lt; 35%</td>
              <td align="center">9 (81,2%)</td>
              <td align="center">7 (26,9%)</td>
              <td align="center"> </td>
              <td align="center">12,2 (2,1-71,0)</td>
            </tr>
            <tr>
              <td>Dias no hospital</td>
              <td align="center">12,0 &#177; 8,7</td>
              <td align="center">6,1&#177;2,1</td>
              <td align="center">0,05</td>
              <td align="center"> </td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn>
            <p>ECG: eletrocardiograma; BNP: pept&#237;deo natriur&#233;tico cerebral.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>Trinta e cinco pacientes tiveram acompanhamento m&#233;dio de 482 &#177; 512 dias. Registramos um
            &#243;bito (acidente vascular cerebral hemorr&#225;gico). N&#227;o foram identificadas reinterna&#231;&#245;es ou
            recorr&#234;ncias de CT. Apenas 22 pacientes (63%) eram assintom&#225;ticos; seis pacientes (16%)
            queixaram-se de dor tor&#225;cica at&#237;pica e doze pacientes (32%) apresentavam classe 2 da
            NYHA (estado funcional pr&#233;-m&#243;rbido classe 1). Todos os pacientes recuperaram fun&#231;&#227;o
            ventricular esquerda normal. Uma resson&#226;ncia magn&#233;tica card&#237;aca foi realizada em treze
            casos e o realce tardio com gadol&#237;nio estava presente em apenas um caso (pequena &#225;rea
            intramioc&#225;rdica).</p>
    </sec>
    <sec sec-type="discussion">
      <title>Discuss&#227;o</title>
      <p>Relatamos as caracter&#237;sticas cl&#237;nicas e os desfechos de todos os pacientes com CT
            consecutivamente admitidos em nosso hospital por um per&#237;odo de 58 meses. Essa &#233; a maior
            coorte portuguesa de centro &#250;nico relatada at&#233; hoje.</p>
      <p>Os dados demogr&#225;ficos de nossa coorte foram semelhantes aos observados em outras partes
            do mundo<xref ref-type="bibr" rid="B05">5</xref><sup>-</sup><xref ref-type="bibr" rid="B08">8</xref>. A maioria dos pacientes era do sexo feminino, na faixa et&#225;ria
            p&#243;s-menopausa. A maioria dos pacientes era hipertensa (73%) e diabetes mellitus era
            menos comum (16%) do que tipicamente observado em s&#237;ndromes coron&#225;rias agudas. Na
            apresenta&#231;&#227;o, dor tor&#225;cica e dispneia foram os sintomas predominantes. Um gatilho
            emocional foi identificado na maioria dos casos, conforme indicado em outros
               estudos<xref ref-type="bibr" rid="B05">5</xref><sup>-</sup><xref ref-type="bibr" rid="B11">11</xref>.</p>
      <p>Nossa popula&#231;&#227;o apresentou uma alta taxa de complica&#231;&#245;es, chegando a 30%, mas n&#227;o houve
            mortes. A taxa de complica&#231;&#227;o relatada em meta-an&#225;lises<xref ref-type="bibr" rid="B03">3</xref><sup>,</sup><xref ref-type="bibr" rid="B07">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref> de CT &#233; de cerca de 19%, com uma taxa de
            mortalidade intrahospitalar global de 0-3,2%<xref ref-type="bibr" rid="B04">4</xref><sup>,</sup><xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B07">7</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref>. O choque cardiog&#234;nico &#233; a complica&#231;&#227;o grave mais comum, ocorrendo em
            6-10% dos pacientes<xref ref-type="bibr" rid="B03">3</xref><sup>,</sup><xref ref-type="bibr" rid="B04">4</xref><sup>,</sup><xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B07">7</xref>. A insufici&#234;ncia
            card&#237;aca congestiva tem sido relatada em 3-46% dos pacientes<xref ref-type="bibr" rid="B02">2</xref>, com edema pulmonar em 16%<xref ref-type="bibr" rid="B07">7</xref>. Arritmias potencialmente fatais, como bloqueio AV de terceiro grau,
            taquicardia ventricular, fibrila&#231;&#227;o ventricular e parada card&#237;aca s&#227;o descritas em 15%
            dos pacientes<xref ref-type="bibr" rid="B07">7</xref>. Casos de forma&#231;&#227;o de trombo
            intramural, gradiente significativo da via de sa&#237;da do VE e ruptura da parede livre do
            ventr&#237;culo esquerdo tamb&#233;m foram observados<xref ref-type="bibr" rid="B02">2</xref><sup>,</sup><xref ref-type="bibr" rid="B05">5</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref><sup>-</sup><xref ref-type="bibr" rid="B15">15</xref>.</p>
      <p>Os dados relativos ao preditores de complica&#231;&#245;es s&#227;o escassos. Madhavan e cols.<xref ref-type="bibr" rid="B16">16</xref> conclu&#237;ram em sua an&#225;lise retrospectiva que a
            idade, estresse f&#237;sico, menor fra&#231;&#227;o de eje&#231;&#227;o e o n&#237;vel de troponina T na admiss&#227;o
            foram preditores independentes de insufici&#234;ncia card&#237;aca aguda. Recentemente Takashio e
               cols.<xref ref-type="bibr" rid="B17">17</xref> identificaram a soma da eleva&#231;&#227;o do
            segmento ST em 12 deriva&#231;&#245;es como um preditor significativo e independente do desfecho
            em CT. No entanto, o padr&#227;o de ECG na admiss&#227;o n&#227;o conferiu qualquer significado
            progn&#243;stico em termos de eventos adversos ou de mortalidade, em outros estudos<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B15">15</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref>.</p>
      <p>Complica&#231;&#245;es agudas em nossa s&#233;rie foram associadas com estresse f&#237;sico, disfun&#231;&#227;o
            ventricular esquerda grave na admiss&#227;o e um BNP mais alto. N&#227;o encontramos nenhuma
            associa&#231;&#227;o com o pico da troponina I, apresenta&#231;&#227;o eletrocardiogr&#225;fica e tempo de
            evolu&#231;&#227;o dos sintomas.</p>
      <p>Embora as recidivas tenham sido relatadas em cerca de 3,5-10% dos casos<xref ref-type="bibr" rid="B03">3</xref><sup>,</sup><xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B19">19</xref>, nenhum dos nossos
            pacientes apresentou recorr&#234;ncia de CT. Ainda n&#227;o est&#225; claro por que a CT n&#227;o ocorre em
            circunst&#226;ncias estressantes semelhantes ap&#243;s o epis&#243;dio inicial.</p>
      <p>Nosso estudo destaca algumas observa&#231;&#245;es importantes. Embora o progn&#243;stico de m&#233;dio a
            longo prazo continue favor&#225;vel na popula&#231;&#227;o com CT, eventos potencialmente fatais
            ocorrem em uma alta porcentagem dos casos. Pacientes submetidos a estresse f&#237;sico, com
            disfun&#231;&#227;o ventricular esquerda grave na admiss&#227;o e n&#237;veis elevados de BNP mereceram
            especial preocupa&#231;&#227;o e vigil&#226;ncia.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclus&#227;o</title>
      <p>A CT tem sido considerada uma forma benigna de insufici&#234;ncia card&#237;aca aguda associada &#224;
            disfun&#231;&#227;o sist&#243;lica transit&#243;ria. No entanto, em nossa popula&#231;&#227;o, uma alta porcentagem de
            pacientes apresentou complica&#231;&#245;es card&#237;acas que justificam a import&#226;ncia do pronto
            reconhecimento e monitora&#231;&#227;o. O estresse f&#237;sico, a fra&#231;&#227;o de eje&#231;&#227;o na admiss&#227;o e os
            n&#237;veis de BNP s&#227;o ferramentas valiosas na estratifica&#231;&#227;o de risco.</p>
    </sec>
    <sec>
      <title>Contribui&#231;&#227;o dos autores</title>
      <p>Concep&#231;&#227;o e desenho da pesquisa: Ribeiro V, Vasconcelos M, Ferreira E, Malangatana G.
            Obten&#231;&#227;o de dados: Ribeiro V, Vasconcelos M, Ferreira E, Malangatana G. An&#225;lise e
            interpreta&#231;&#227;o dos dados: Ribeiro V, Vasconcelos M. An&#225;lise estat&#237;stica: Mel&#227;o F. Reda&#231;&#227;o
            do manuscrito: Ribeiro V, Vasconcelos M. Revis&#227;o cr&#237;tica do manuscrito quanto ao
            conte&#250;do intelectual: Vasconcelos M, Mel&#227;o F, Maciel MJ.</p>
    </sec>
  </body>
  <back>
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    <fn-group>
      <fn fn-type="other">
        <p>
          <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
        </p>
        <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
      </fn>
      <fn fn-type="financial-disclosure">
        <p>
          <bold>Fontes de Financiamento</bold>
        </p>
        <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
      </fn>
    </fn-group>
  </back>
  <sub-article id="SA1" article-type="translation" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Short and Long-Term Outcome of Stress-Induced
               Cardiomyopathy: What Can We Expect?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Ribeiro</surname>
            <given-names>V&#226;nia Filipa Andrade</given-names>
          </name>
          <xref ref-type="aff" rid="aff03">1</xref>
          <xref ref-type="corresp" rid="c02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Vasconcelos</surname>
            <given-names>Mariana</given-names>
          </name>
          <xref ref-type="aff" rid="aff03">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mel&#227;o</surname>
            <given-names>Filipa</given-names>
          </name>
          <xref ref-type="aff" rid="aff03">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ferreira</surname>
            <given-names>Ester</given-names>
          </name>
          <xref ref-type="aff" rid="aff03">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Malangatana</surname>
            <given-names>Gracieta</given-names>
          </name>
          <xref ref-type="aff" rid="aff04">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Maciel</surname>
            <given-names>Maria J&#250;lia</given-names>
          </name>
          <xref ref-type="aff" rid="aff03">1</xref>
        </contrib>
      </contrib-group>
      <aff id="aff03">
        <label>1</label>
        <institution content-type="orgname">Centro Hospitalar S&#227;o Jo&#227;o</institution>
        <addr-line>
          <named-content content-type="city">Porto</named-content>
        </addr-line>
        <country>Portugal</country>
        <institution content-type="original">Centro Hospitalar S&#227;o Jo&#227;o, Porto -
               Portugal</institution>
      </aff>
      <aff id="aff04">
        <label>2</label>
        <institution content-type="orgname">Hospital Pedro Hispano</institution>
        <addr-line>
          <named-content content-type="city">Porto</named-content>
        </addr-line>
        <country>Portugal</country>
        <institution content-type="original">Hospital Pedro Hispano, Porto -
               Portugal</institution>
      </aff>
      <author-notes>
        <corresp id="c02"><bold>Mailing Address: V&#226;nia Filipa Andrade Ribeiro,</bold> Alameda Prof. H&#234;rnani
               Monteiro. Postal Code 4200-319, Porto - Portugal. E-mail:
                  <email>ribeiro_vania@hotmail.com</email>
            </corresp>
        <fn fn-type="conflict">
          <p>
            <bold>Potential Conflict of Interest</bold>
          </p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <abstract xml:lang="en">
        <sec>
          <title>Background:</title>
          <p>Stress-induced/Takotsubo cardiomyopathy (TC) is an increasingly recognized
                  diagnostic entity.</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p>This study was aimed to assess the prevalence and clinical predictors of short and
                  long-term outcome of patients (pts) diagnosed with TC.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>We included all consecutive pts admitted in our department, from November 2006 to
                  August 2011, who met the Mayo Clinic criteria for TC diagnosis.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>We evaluated 37 pts (35 women) with a mean age of 63 &#177;13 years. TC was
                  precipitated by a stressful emotional event in the majority (57%) and chest pain
                  was the most common symptom (89%). Twelve pts (32%) had ST-segment elevation and
                  15 pts (41%) had T-wave inversion on the electrocardiogram at admission. Severe
                  left ventricular (LV) dysfunction was found in 16 pts (43%) and the mean troponin
                  I level was 2.6&#177;1.8 ng/mL. The in-hospital complication rate was 30%, with
                  cardiogenic shock being the most common situation. Physical stress, severe LV
                  systolic dysfunction and peak brain natriuretic peptide (BNP) were predictors of
                  acute complications. On the other hand, we found no association between peak
                  troponin I and electrocardiographic presentation. Thirty-five pts were followed
                  for a mean time of 482 &#177; 512 days, without clinic recurrence.</p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p>In our cohort of pts, TC was associated with a high in-hospital complications
                  rate. Physical stress, LV dysfunction and peak BNP could predict acute adverse
                  outcomes.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Takotsubo cardiomyopathy</kwd>
        <kwd>Stress, Psychological</kwd>
      </kwd-group>
      <counts>
        <fig-count count="2"/>
        <table-count count="3"/>
        <equation-count count="0"/>
        <ref-count count="19"/>
        <page-count count="6"/>
      </counts>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>Stress-induced/Takotsubo cardiomyopathy (TC) is an increasingly reported syndrome
               characterized by transient systolic dysfunction in the absence of obstructive
               coronary disease, which mimics myocardial infarction.</p>
        <p>The precise incidence of SC is unknown, but recent studies have shown a prevalence of
               approximately 2% of patients presenting with acute coronary syndrome in the United
               States and Europe<xref ref-type="bibr" rid="B01">1</xref>.</p>
        <p>An emotional or physical stressor frequently precedes the development of symptoms,
               but the pathophysiology of TC is unclear. Several hypotheses have been proposed,
               including catecholamine-mediated cardiotoxicity, spasm of the microvascular coronary
               circulation and endothelial cell dysfunction<xref ref-type="bibr" rid="B02">2</xref><sup>-</sup><xref ref-type="bibr" rid="B04">4</xref>.</p>
        <p>In this report we evaluate the clinical features of 37 patients with this disorder,
               consecutively admitted in our tertiary hospital center, and the predictors of adverse
               events at short and long-term in this population.</p>
      </sec>
      <sec sec-type="methods">
        <title>Methods</title>
        <p>From November 2006 to August 2011, we retrospectively identified 37 patients with TC
               who had undergone left heart catheterization for acute coronary syndrome in our
               tertiary hospital center. All patients presented to our emergency department or were
               transferred from an outside hospital. The inclusion criteria for Takotsubo
               cardiomyopathy, according to the Mayo Clinic, were: transient LV wall motion
               abnormalities involving the apical/ and or midventricular myocardial segments with
               wall motion abnormalities extending beyond a single epicardial coronary distribution;
               absence of obstructive epicardial coronary artery disease or angiographic evidence of
               acute plaque rupture that could be responsible for the observed wall motion
               abnormality; new ECG abnormalities such as transient ST-segment elevation and/or
               diffuse T-wave inversions or troponin elevation; absence of pheochromocytoma or
               myocarditis.</p>
        <p>The patients' demographics, clinical presentation, electrocardiographic findings,
               cardiac biomarker levels and complications were assessed during hospital stay. All
               patients underwent left ventriculography and echocardiographic evaluation, at
               admission and follow-up. Clinical follow-up was performed with outpatient visits.
               Cardiac magnetic resonance was performed in thirteen patients. Recurrence of
               symptoms, re-hospitalization, functional status and death were recorded.</p>
        <p>Data was analyzed using SPSS version 20.0 and the association between baseline
               variables and acute complications was estimated through odds ratio (OR) for
               categorical variables and paired T test for continuous variables.</p>
      </sec>
      <sec sec-type="results">
        <title>Results</title>
        <p>Thirty-five patients (95%) were women with a mean age of 63 &#177; 13 years (<xref ref-type="table" rid="t04">Table 1</xref>). The majority of patients had
               cardiovascular risk factors: twenty-seven patients (73%) had hypertension, nineteen
               (51%) had dyslipidemia and six (16%) had diabetes. The most common presentation was
               chest pain (89%), but three patients (8%) presented with dyspnea and one (3%)
               presented with lipothymy. A trigger was identified in twenty-nine patients (78%). The
               commonest trigger was emotional stress (57%). A physical trigger was present in eight
               patients (22%) and included an elective surgical procedure, chronic obstructive
               pulmonary disease exacerbation and recent hospitalization. The admission ECG revealed
               ST-segment elevation in twelve patients (32%) and widespread T-wave inversion in
               twenty-five patients (41%) (<xref ref-type="fig" rid="f03">Figure 1</xref>). Other
               ECG findings included sinus tachycardia and new Q waves. Five patients (14%) had no
               ECG alterations. Troponin I was positive in all cases with a mean peak level of 2.6 &#177;
               1.8 ng/mL. Mean peak value of brain natriuretic peptide (BNP) was 1160 &#177; 1564 pg/mL.
               Left ventricular assessment demonstrated the classical apical ballooning appearance
               in thirty-four patients (92%) and mid-wall variant was demonstrated in three patients
               (8%) (<xref ref-type="fig" rid="f04">Figure 2</xref>). The mean ejection fraction by
               echocardiography was 40%.</p>
        <table-wrap id="t04">
          <label>Table 1</label>
          <caption>
            <title>Baseline characteristics of the study population</title>
          </caption>
          <table frame="hsides" rules="rows">
            <thead>
              <tr>
                <th align="left">
                  <bold>Characteristic</bold>
                </th>
                <th>
                  <bold>Total (n = 37) Value</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>Age (years), mean &#177; SD</td>
                <td align="center">63 &#177; 13</td>
              </tr>
              <tr>
                <td>Female</td>
                <td align="center">35 (95%)</td>
              </tr>
              <tr>
                <td colspan="2">
                  <bold>Cardiovascular risk factors</bold>
                </td>
              </tr>
              <tr>
                <td>Diabetes mellitus</td>
                <td align="center">6 (16%)</td>
              </tr>
              <tr>
                <td>Hypertension</td>
                <td align="center">27 (73%)</td>
              </tr>
              <tr>
                <td>Dyslipidemia</td>
                <td align="center">19 (51%)</td>
              </tr>
              <tr>
                <td>Smoking (actual or previous)</td>
                <td align="center">2 (5%)</td>
              </tr>
              <tr>
                <td colspan="2">
                  <bold>Clinical presentation</bold>
                </td>
              </tr>
              <tr>
                <td>Chest pain</td>
                <td align="center">33 (89%)</td>
              </tr>
              <tr>
                <td>Dyspnea</td>
                <td align="center">3 (8%)</td>
              </tr>
              <tr>
                <td>Lipothymy</td>
                <td align="center">1(3%)</td>
              </tr>
              <tr>
                <td colspan="2">
                  <bold>Triggering factor</bold>
                </td>
              </tr>
              <tr>
                <td>Emotional stress</td>
                <td align="center">21 (57%)</td>
              </tr>
              <tr>
                <td>Physical stress</td>
                <td align="center">8 (22%)</td>
              </tr>
              <tr>
                <td>No trigger</td>
                <td align="center">8 (22%)</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn>
              <p>SD: standard deviation.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <fig id="f03" fig-type="other">
          <label>Figure 1</label>
          <caption>
            <title>Representative electrocardiographic patterns at admission with (A)
                     ST-segment elevation in V2 to V6 and (B) T wave inversion in V2 to V5, DI and
                     aVL.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-102-01-0080-30228-gf01-en.jpg"/></fig>
        <fig id="f04" fig-type="other">
          <label>Figure 2</label>
          <caption>
            <title>Left ventriculogram at (A) end-systole and (B) end-diastole, showing a
                     mid-wall variant with apical contraction.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-102-01-0080-30228-gf02-en.jpg"/></fig>
        <p>Acute complications occurred in eleven patients (30%), with cases presenting more
               than one complication (<xref ref-type="table" rid="t05">Table 2</xref>). Cardiogenic
               shock was the most common situation, but two patients developed acute pulmonary
               edema. Rhythm disturbances were also observed. One patient had an episode of rapid
               atrial fibrillation, cardioverted with amiodarone. Third-degree AV block was
               documented in two patients, one of them requiring a permanent pacemaker due to the
               persistence of AV block after recovery of the systolic function. The
               echocardiographic evaluation performed in all patients identified two cases of
               significant LV outflow gradient and two cases of intraventricular thrombus.</p>
        <table-wrap id="t05">
          <label>Table 2</label>
          <caption>
            <title>In-hospital complications in the study population</title>
          </caption>
          <table frame="hsides" rules="rows">
            <thead>
              <tr>
                <th align="left">
                  <bold>In-hospital complication</bold>
                </th>
                <th>
                  <bold>n (%)</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>Cardiogenic shock</td>
                <td align="center">4 (11%)</td>
              </tr>
              <tr>
                <td>Intraventricular thrombus</td>
                <td align="center">2 (5%)</td>
              </tr>
              <tr>
                <td>Atrial fibrillation</td>
                <td align="center">1 (3%)</td>
              </tr>
              <tr>
                <td>Pulmonary edema</td>
                <td align="center">2 (5%)</td>
              </tr>
              <tr>
                <td>Third degree AV-block</td>
                <td align="center">2 (5%)</td>
              </tr>
              <tr>
                <td>Significant left ventricular outflow gradient</td>
                <td align="center">2 (5%)</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn>
              <p>AV: atrioventricular.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>There were no deaths. The mean duration of hospital stay was 7.9 &#177; 5.6 days, with
               longer hospitalization in patients with complications (12.0 &#177; 8.7 vs. 6.1 &#177; 2.1, p =
               0.05), as expected. Physical stress (odds ratio: 6.4; 95% confidence interval: 1.2 to
               34.6), severe LV systolic function at admission (odds ratio: 12.2; 95% confidence
               interval: 2.1-71.0) and peak BNP (2324.7 &#177; 2107.2 vs. 512.8 &#177; 542.9, p = 0.024) were
               predictors of acute complications. On the other hand, we found no association between
               peak troponin I, electrocardiographic presentation and time of symptom evolution
                  (<xref ref-type="table" rid="t06">Table 3</xref>).</p>
        <table-wrap id="t06">
          <label>Table 3</label>
          <caption>
            <title>Clinical predictors of in-hospital complications in the study
                     population</title>
          </caption>
          <table frame="hsides" rules="rows">
            <thead>
              <tr>
                <th> </th>
                <th>
                  <bold>Acute complications (n = 11)</bold>
                </th>
                <th>
                  <bold>No acute complications (n = 26)</bold>
                </th>
                <th>
                  <bold>p value</bold>
                </th>
                <th>
                  <bold>OR 95% CI</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>Age (years)</td>
                <td align="center">63.2 &#177; 20.3</td>
                <td align="center">63.0 &#177; 8.9</td>
                <td align="center">0.98</td>
                <td align="center"> </td>
              </tr>
              <tr>
                <td>Triggering factor</td>
                <td align="center"> </td>
                <td align="center"> </td>
                <td align="center">0.03</td>
                <td align="center"> </td>
              </tr>
              <tr>
                <td>Emotional stress</td>
                <td align="center">3 (27.3%)</td>
                <td align="center">18 (69.2%)</td>
                <td align="center"> </td>
                <td align="center"> </td>
              </tr>
              <tr>
                <td>Physical stress</td>
                <td align="center">5 (45.5%)</td>
                <td align="center">3 (11.5%)</td>
                <td align="center"> </td>
                <td align="center">6.4 (1.2-34.6)</td>
              </tr>
              <tr>
                <td>No trigger</td>
                <td align="center">3 (27.3%)</td>
                <td align="center">5 (19.2%)</td>
                <td align="center"> </td>
                <td align="center"> </td>
              </tr>
              <tr>
                <td>Time from symptoms onset (hours)</td>
                <td align="center">16.6 &#177; 18.5</td>
                <td align="center">9.83 &#177; 16.2</td>
                <td align="center">0.28</td>
                <td align="center"> </td>
              </tr>
              <tr>
                <td>ECG presentation</td>
                <td align="center"> </td>
                <td align="center"> </td>
                <td align="center">0.49</td>
                <td align="center"> </td>
              </tr>
              <tr>
                <td>Normal ECG</td>
                <td align="center">3 (27.3%)</td>
                <td align="center">2 (7.7%)</td>
                <td align="center"> </td>
                <td align="center"> </td>
              </tr>
              <tr>
                <td>ST-segment elevation 3</td>
                <td align="center">3 (27.3%)</td>
                <td align="center">9 (34.6%)</td>
                <td align="center"> </td>
                <td align="center"> </td>
              </tr>
              <tr>
                <td>Negative T waves</td>
                <td align="center">3 (27.3%)</td>
                <td align="center">12 (46.2%)</td>
                <td align="center"> </td>
                <td align="center"> </td>
              </tr>
              <tr>
                <td>Troponin I peak (ng/mL)</td>
                <td align="center">2.5 &#177; .8</td>
                <td align="center">2.6 &#177; 1.8</td>
                <td align="center">0.98</td>
                <td align="center"> </td>
              </tr>
              <tr>
                <td>BNP peak (pg/mL)</td>
                <td align="center">2324.7 &#177; 2107.2</td>
                <td align="center">512.8 &#177; 542.9</td>
                <td align="center">0.02</td>
                <td align="center"> </td>
              </tr>
              <tr>
                <td>Ejection fraction</td>
                <td align="center"> </td>
                <td align="center"> </td>
                <td align="center">0.02</td>
                <td align="center"> </td>
              </tr>
              <tr>
                <td>&#8805; 45%-55%</td>
                <td align="center">1 (9.1%)</td>
                <td align="center">2 (7.7%)</td>
                <td align="center"> </td>
                <td align="center"> </td>
              </tr>
              <tr>
                <td>&#8805; 35%-45%</td>
                <td align="center">1 (9.1%)</td>
                <td align="center">16 (61.5%)</td>
                <td align="center"> </td>
                <td align="center"> </td>
              </tr>
              <tr>
                <td>&lt; 35%</td>
                <td align="center">9 (81.2%)</td>
                <td align="center">7 (26.9%)</td>
                <td align="center"> </td>
                <td align="center">12.2 (2.1-71.0)</td>
              </tr>
              <tr>
                <td>Days in hospital</td>
                <td align="center">12.0 &#177; 8.7</td>
                <td align="center">6.1&#177;2.1</td>
                <td align="center">0.05</td>
                <td align="center"> </td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn>
              <p>ECG: electrocardiogram; BMP: Brain natricuretic peptide.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Thirty-five patients had follow-up at mean time of 482 &#177; 512 days. We recorded one
               death (hemorrhagic cerebrovascular event). No rehospitalizations or TC recurrences
               were identified. Only 22 patients (63%) were asymptomatic; six patients (16%)
               complained of atypical chest pain and twelve patients (32%) were in NYHA class 2
               (premorbid class 1 functional status). All patients recovered normal left ventricular
               function. Cardiac magnetic resonance was performed in thirteen cases and late
               gadolinium enhancement was present in only one case (small intramyocardial area).</p>
      </sec>
      <sec sec-type="discussion">
        <title>Discussion</title>
        <p>We report the clinical features and outcomes of all TC patients consecutively
               admitted in our hospital over a period of 58 months. This is the largest
               single-center Portuguese cohort reported to date.</p>
        <p>The demographics of our cohort were similar to that observed in other parts of the
                  world<xref ref-type="bibr" rid="B05">5</xref><sup>-</sup><xref ref-type="bibr" rid="B08">8</xref>. Most patients were female in the post menopausal age group.
               The majority of patients were hypertensive (73%) and diabetes mellitus was less
               common (16%) than typically seen in acute coronary syndromes. At presentation, chest
               pain and dyspnea were the prevalent symptoms. An emotional trigger could be
               identified in most cases, as seen in other studies<xref ref-type="bibr" rid="B05">5</xref><sup>-</sup><xref ref-type="bibr" rid="B11">11</xref>.</p>
        <p>Our population had a high complication rate, reaching 30%, but there were no deaths.
               The reported complication rate in meta-analyses<xref ref-type="bibr" rid="B03">3</xref><sup>,</sup><xref ref-type="bibr" rid="B07">7</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12 </xref>of TC is about 19%, with an overall
               in-hospital mortality rate of 0-3.2%<xref ref-type="bibr" rid="B04">4</xref><sup>,</sup><xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B07">7</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref>. Cardiogenic shock is the most common severe complication, occurring in
               6-10% of patients<xref ref-type="bibr" rid="B03">3</xref><sup>,</sup><xref ref-type="bibr" rid="B04">4</xref><sup>,</sup><xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B07">7</xref>. Congestive heart
               failure has been reported in 3-46% of patients<xref ref-type="bibr" rid="B02">2</xref>, with pulmonary edema in 16%<xref ref-type="bibr" rid="B07">7</xref>.
               Life-threatening arrhythmias such as third degree AV-block, ventricular tachycardia,
               ventricular fibrillation and cardiac arrest are described in 15% of patients<xref ref-type="bibr" rid="B07">7</xref>. Cases of intramural thrombus formation,
               significant LV outflow gradient and left ventricular free-wall rupture have also been
                  observed<xref ref-type="bibr" rid="B02">2</xref><sup>,</sup><xref ref-type="bibr" rid="B05"> 5</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref><sup>-</sup><xref ref-type="bibr" rid="B15">15</xref>.</p>
        <p>Data related to predictors of complications are scarce. Madhavan et al<xref ref-type="bibr" rid="B16">16</xref> concluded in their retrospective analysis that
               age, physical stress, lower ejection fraction and admission troponin T level were
               independent predictors of acute heart failure. Recently, Takashio et al<xref ref-type="bibr" rid="B17">17</xref> identified the sum of ST-segment elevation in
               12 leads as a significant and independent predictor of outcome in TC. However the ECG
               pattern on admission did not confer any prognostic significance in terms of adverse
               events or mortality, in other studies<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B15">15</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref>.</p>
        <p>Acute complications in our series were associated with physical stress, severe LV
               dysfunction at admission and higher BNP level. We found no association with peak
               troponin I, electrocardiographic presentation and time of symptom evolution.</p>
        <p>Although recurrences have been reported in about 3.5-10% of cases<xref ref-type="bibr" rid="B03">3</xref><sup>,</sup><xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B19">19</xref>, none of our
               patients had TC recurrence. It remains unclear why TC does not reoccur in similar
               stressful circumstances after the initial episode.</p>
        <p>Our study highlights some important observations. Although medium- to long-term
               prognosis remains favorable in TC populations, life-threatening events occur in a
               high percentage of cases. Patients submitted to physical stress, with severe LV
               dysfunction at admission and elevated BNP deserved particular concern and
               surveillance.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclusion</title>
        <p>TC has been regarded as a benign form of acute heart failure associated with
               transitory systolic dysfunction. However, in our population, a high percentage of
               patients experienced cardiac complications justifying the importance of prompt
               recognition and tight surveillance. Physical stress, ejection fraction at admission
               and BNP levels are valuable tools in risk stratification.</p>
      </sec>
      <sec>
        <title>Author contributions</title>
        <p>Conception and design of the research: Ribeiro V, Vasconcelos M, Ferreira E,
               Malangatana G. Acquisition of data: Ribeiro V, Vasconcelos M, Ferreira E, Malangatana
               G. Analysis and interpretation of the data: Ribeiro V, Vasconcelos M. Statistical
               analysis: Mel&#227;o F. Writing of the manuscript: Ribeiro V, Vasconcelos M. Critical
               revision of the manuscript for intellectual content: Vasconcelos M, Mel&#227;o F, Maciel
               MJ.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other">
          <p>
            <bold>Study Association</bold>
          </p>
          <p>This study is not associated with any post-graduation program.</p>
        </fn>
        <fn fn-type="financial-disclosure">
          <p>
            <bold>Sources of Funding</bold>
          </p>
          <p>There were no external funding sources for this study.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
