<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.1 20151215//EN" "https://jats.nlm.nih.gov/publishing/1.1/JATS-journalpublishing1.dtd">
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="editorial" dtd-version="1.1" specific-use="sps-1.9" xml:lang="pt">
  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id specific-use="scielo-v3" pub-id-type="publisher-id">YM7xqYXqjxBJJGXxZnPM4fR</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2020000900217</article-id>
      <article-id pub-id-type="publisher-id">abc.20200470</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20200470</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>A S&#237;ndrome de Takotsubo Existe como uma Doen&#231;a Espec&#237;fica?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-6718-8456</contrib-id>
          <name>
            <surname>Caramelli</surname>
            <given-names>Bruno</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
        <institution content-type="orgdiv1">Instituto do Cora&#231;&#227;o</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Universidade de S&#227;o Paulo &#8211; Instituto do Cora&#231;&#227;o (InCor),S&#227;o Paulo, SP &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c01"> Correspond&#234;ncia: Bruno Caramelli &#8226; Universidade de S&#227;o Paulo &#8211; Instituto do Cora&#231;&#227;o (InCor) - Av. Dr. Eneas C. de Aguiar, 44. CEP 05403-000, S&#227;o Paulo, SP &#8211; Brasil. E-mail: <email>bcaramel@usp.br</email> , <email>brunoc@cardiol.br</email> </corresp>
      </author-notes>
      <pub-date publication-format="electronic" date-type="pub">
        <day>28</day>
        <month>08</month>
        <year>2020</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>08</month>
        <year>2020</year>
      </pub-date>
      <volume>115</volume>
      <issue>2</issue>
      <fpage>217</fpage>
      <lpage>218</lpage>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p> This is an Open Access article distributed under the terms of the Creative Commons Attribution 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>
      <kwd-group xml:lang="pt">
        <kwd>Cardiomiopatia de Takotsubo</kwd>
        <kwd>Disfun&#231;&#227;o Ventricular</kwd>
        <kwd>Doen&#231;a Arterial Coronariana</kwd>
        <kwd>Diagn&#243;stico Diferencial</kwd>
        <kwd>Diagn&#243;stico por Imagem</kwd>
      </kwd-group>
      <counts>
        <fig-count count="2"/>
        <table-count count="2"/>
        <equation-count count="0"/>
        <ref-count count="6"/>
        <page-count count="2"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>O nome &#8220;s&#237;ndrome&#8221; combina duas ra&#237;zes gregas para descrever uma condi&#231;&#227;o que re&#250;ne um grupo de sinais e sintomas que existem juntos nos pacientes. Parece que Avicenna o utilizou pela primeira vez em sua publica&#231;&#227;o de 1025, &#8220; <italic>The Canon of Medicine</italic> &#8221;.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Em gen&#233;tica, o uso da palavra &#8220;s&#237;ndrome&#8221; geralmente pressup&#245;e que a causa subjacente da doen&#231;a seja conhecida. Por outro lado, em medicina, a s&#237;ndrome refere-se a condi&#231;&#245;es de causa conhecida e desconhecida.</p>
    <p>Historicamente, os sinais e sintomas associados considerados de correla&#231;&#227;o improv&#225;vel acabaram sendo conhecidos por terem uma causa subjacente respons&#225;vel por todos eles. Mesmo depois que a causa &#233; revelada, a palavra original permanece, &#224;s vezes com o nome do primeiro descritor, e essa &#233; provavelmente a raz&#227;o da exist&#234;ncia hoje em dia de s&#237;ndromes com causas identificadas e n&#227;o identificadas.</p>
    <p>Nesta edi&#231;&#227;o, os &#8220;Arquivos Brasileiros de Cardiologia&#8221; publicam o artigo intitulado &#8220;Registro multic&#234;ntrico de Takotsubo (REMUTA) &#8211; Aspectos cl&#237;nicos,</p>
    <p>Desfechos intra-hospitalares e mortalidade em longo prazo.&#8221;<sup><xref ref-type="bibr" rid="B2">2</xref></sup> A s&#237;ndrome de Takotsubo foi relatada inicialmente por Sato et al., em 1990, no Jap&#227;o, descrevendo 16 casos que compartilhavam sinais e sintomas conhecidos: dor tor&#225;cica t&#237;pica ap&#243;s um evento estressante e art&#233;rias coron&#225;rias &#8220;angiograficamente normais&#8221;.</p>
    <p>O Registro Multic&#234;ntrico de Takotsubo (REMUTA) adotou os crit&#233;rios de diagn&#243;stico da for&#231;a-tarefa sobre a s&#237;ndrome de Takotsubo da &#8220; <italic>Heart Failure Association of the European Society of Cardiology</italic> &#8221;, publicada em 2016.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> De acordo com esses crit&#233;rios, se a les&#227;o coronariana culpada for identificada, o diagn&#243;stico de s&#237;ndrome coronariana aguda &#233; estabelecido e a s&#237;ndrome de Takotsubo &#233; descartada. No registro REMUTA, todos os pacientes foram submetidos &#224; angiografia coronariana e 24,2% deles apresentaram doen&#231;a arterial coronariana n&#227;o-obstrutiva, definida pelos autores como menos de 50% de obstru&#231;&#245;es. Os 75,8% restantes tinham, segundo os autores, art&#233;rias coron&#225;rias &#8220;angiograficamente normais&#8221;. Entretanto, n&#227;o h&#225; refer&#234;ncia &#224; aus&#234;ncia de les&#227;o coronariana culpada nos pacientes estudados, crit&#233;rio necess&#225;rio para o diagn&#243;stico da s&#237;ndrome de Takotsubo, conforme declarado no primeiro consenso de 2016, adotado pelo estudo REMUTA.</p>
    <p>Acima, a express&#227;o &#8220;angiograficamente normal&#8221; est&#225; entre aspas de prop&#243;sito, por um motivo: a defini&#231;&#227;o de art&#233;rias coron&#225;rias angiograficamente normais &#233; um desafio para ser estabelecido. Existem limita&#231;&#245;es relacionadas &#224; resolu&#231;&#227;o dos m&#233;todos de imagem e ao conceito bem conhecido de que mesmo as placas ateroscler&#243;ticas sutis podem desencadear trombose coronariana. Al&#233;m disso, a disfun&#231;&#227;o endotelial que afeta as art&#233;rias coron&#225;rias epic&#225;rdicas ou suas ramifica&#231;&#245;es endoc&#225;rdicas pode ser respons&#225;vel pelo desenvolvimento de s&#237;ndromes coronarianas agudas (SCA). De fato, um consenso internacional sobre imagens intracoronarianas, publicado em 2019, afirma que a les&#227;o culpada n&#227;o pode ser identificada em 4-10% dos pacientes com SCA com supradesnivelamento do segmento ST e em &gt;30% dos pacientes sem supradesnivelamento do segmento ST.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> Considerando essas advert&#234;ncias, mesmo ap&#243;s modifica&#231;&#245;es, a defini&#231;&#227;o angiogr&#225;fica da s&#237;ndrome de Takotsubo n&#227;o oferece um crit&#233;rio &#224; beira do leito seguro para a pr&#225;tica cl&#237;nica. Talvez por esse motivo, em 2018, a defini&#231;&#227;o original da s&#237;ndrome de Takotsubo, sugerida por Sato et al. foi modificada novamente, e o novo consenso afirmou que doen&#231;a arterial coronariana significativa n&#227;o &#233; mais uma contradi&#231;&#227;o para o diagn&#243;stico da s&#237;ndrome de Takotsubo.<sup><xref ref-type="bibr" rid="B5">5</xref></sup></p>
    <p>Na Medicina, &#233; de suma import&#226;ncia ter condi&#231;&#245;es de sa&#250;de com defini&#231;&#245;es claras para o diagn&#243;stico diferencial, estratifica&#231;&#227;o de risco e como refer&#234;ncia para estudos futuros em pesquisas cl&#237;nicas. Esse princ&#237;pio abriu o caminho para o estabelecimento dos conceitos agora centrais de s&#237;ndromes coronarianas agudas com supradesnivelamento e sem supradesnivelamento do segmento ST, por exemplo. &#192; beira do leito, os cardiologistas modernos sabem como estratificar o risco e dar tratamento adequado para ambas as condi&#231;&#245;es. Este n&#227;o &#233; o caso da s&#237;ndrome de Takotsubo, que n&#227;o pode ser indiscutivelmente diferenciada das s&#237;ndromes coron&#225;rias agudas. Como pode ser observado na <xref ref-type="table" rid="t1">Tabela 1</xref> , exceto pelo aumento da preval&#234;ncia em mulheres na p&#243;s-menopausa, todos os outros crit&#233;rios est&#227;o presentes nas duas s&#237;ndromes e as diferen&#231;as s&#227;o baseadas em opini&#245;es subjetivas tomadas na frente do paciente. Na aus&#234;ncia de crit&#233;rios objetivos, o diagn&#243;stico diferencial &#233; desafiador e os pacientes podem ser diagnosticados erroneamente. Apesar de considerar muito importante ter um Registro Nacional de uma doen&#231;a espec&#237;fica (e parabenizo os autores por esse esfor&#231;o), o leitor n&#227;o pode excluir a possibilidade de alguns pacientes no registro REMUTA terem o diagn&#243;stico de SCA em vez de S&#237;ndrome de Takotsubo.</p>
    <p>
      <table-wrap id="t1">
        <label>Tabela 1</label>
        <caption>
          <title>&#8211; Gr&#225;fico de compara&#231;&#227;o de crit&#233;rios diagn&#243;sticos entre a s&#237;ndrome de Takotsubo e s&#237;ndrome coronariana aguda</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup width="33%">
            <col/>
            <col/>
            <col/>
          </colgroup>
          <thead>
            <tr>
              <th align="left">Crit&#233;rios diagn&#243;sticos</th>
              <th>Takotsubo</th>
              <th>S&#237;ndrome coronariana aguda</th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td>Disfun&#231;&#227;o transit&#243;ria do ventr&#237;culo esquerdo</td>
              <td align="center">+++</td>
              <td align="center">+</td>
            </tr>
            <tr>
              <td>Gatilho emocional / f&#237;sico</td>
              <td align="center">++</td>
              <td align="center">+</td>
            </tr>
            <tr>
              <td>Dist&#250;rbios neurol&#243;gicos como gatilho</td>
              <td align="center">++</td>
              <td align="center">+</td>
            </tr>
            <tr>
              <td>Novas anormalidades no ECG</td>
              <td align="center">++</td>
              <td align="center">+++</td>
            </tr>
            <tr>
              <td>Biomarcadores card&#237;acos elevados</td>
              <td align="center">+</td>
              <td align="center">+++</td>
            </tr>
            <tr>
              <td>Descartar miocardite por infec&#231;&#227;o</td>
              <td align="center">+</td>
              <td align="center">+</td>
            </tr>
            <tr>
              <td>Mais frequente em mulheres na p&#243;s-menopausa</td>
              <td align="center">+</td>
              <td align="center">-</td>
            </tr>
            <tr>
              <td>Doen&#231;a arterial coronariana significativa</td>
              <td align="center">+</td>
              <td align="center">+++</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
    </p>
    <p>Em resumo, o diagn&#243;stico correto da s&#237;ndrome de Takotsubo muitas vezes permanece indefinido. Por outro lado, dados recentes mostraram que a resson&#226;ncia magn&#233;tica tem um papel promissor na s&#237;ndrome de Takotsubo e pode representar, no futuro, a base para o diagn&#243;stico diferencial.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> As s&#237;ndromes coronarianas agudas representam hoje um grande e importante grupo de doen&#231;as card&#237;acas, cada uma com caracter&#237;sticas e tratamento espec&#237;ficos. A s&#237;ndrome de Takotsubo, pelo contr&#225;rio, ainda carece de uma identidade definitiva. Ela &#233; uma doen&#231;a espec&#237;fica e independente ou uma apresenta&#231;&#227;o peculiar de uma s&#237;ndrome coronariana aguda? Como na vers&#227;o hebraica da hist&#243;ria de Jonas na B&#237;blia, a Takotsubo deve nadar mais r&#225;pido, ficar mais forte e crescer; caso contr&#225;rio, ser&#225; engolida pelo peixe gigante.</p>
    <p>
      <fig id="f01">
        <label>Figura 1</label>
        <caption>
          <title>&#8211; <italic>Como na vers&#227;o hebraica da hist&#243;ria de Jonas na B&#237;blia, a Takotsubo deve nadar mais r&#225;pido, ficar mais forte e crescer; caso contr&#225;rio, ser&#225; engolida pelo peixe gigante. Arte de Piero de Souza Dias Caramellli.</italic></title>
        </caption>
        <graphic xlink:href="1678-4170-abc-115-02-0217-00470-gf01.tif"/></fig>
    </p>
  </body>
  <back>
    <ref-list>
      <title>Refer&#234;ncias</title>
      <ref id="B1">
        <label>1</label>
        <mixed-citation>1. Wikipedia [internet]. Syndrome [Citado em 13 maio 2020]. Dispon&#237;vel em: <ext-link ext-link-type="uri" xlink:href="https://en.wikipedia.org/wiki/Syndrome">https://en.wikipedia.org/wiki/Syndrome</ext-link>.</mixed-citation>
        <element-citation publication-type="webpage">
          <person-group person-group-type="author">
            <collab>Wikipedia</collab>
          </person-group>
          <comment>internet</comment>
          <source>Syndrome</source>
          <date-in-citation content-type="cited-date">Citado em 13 maio 2020</date-in-citation>
          <comment>
            <ext-link ext-link-type="uri" xlink:href="https://en.wikipedia.org/wiki/Syndrome">https://en.wikipedia.org/wiki/Syndrome</ext-link>
          </comment>
        </element-citation>
      </ref>
      <ref id="B2">
        <label>2</label>
        <mixed-citation>2. Almeida Junior GLG, Mansur Filho J, Albuquerque DC, Xavier SS, Pontes A, Gouv&#234;a EP, et al. Takotsubo Multicenter Registry (REMUTA) &#8211; Clinical Aspects, In-Hospital Outcomes, and Long-Term Mortality. Arq Bras Cardiol. 2020; 115(2):207-216).</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Almeida</surname>
              <given-names>GLG</given-names>
              <suffix>Junior</suffix>
            </name>
            <name>
              <surname>Mansur</surname>
              <given-names>J</given-names>
              <suffix>Filho</suffix>
            </name>
            <name>
              <surname>Albuquerque</surname>
              <given-names>DC</given-names>
            </name>
            <name>
              <surname>Xavier</surname>
              <given-names>SS</given-names>
            </name>
            <name>
              <surname>Pontes</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Gouv&#234;a</surname>
              <given-names>EP</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Takotsubo Multicenter Registry (REMUTA) &#8211; Clinical Aspects, In-Hospital Outcomes, and Long-Term Mortality</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2020</year>
          <volume>115</volume>
          <issue>2</issue>
          <fpage>207</fpage>
          <lpage>216</lpage>
        </element-citation>
      </ref>
      <ref id="B3">
        <label>3</label>
        <mixed-citation>3. Lyon AR, Bossone E, Schneider B, Sechtem U, Citro R, Underwood SR, et al. Current state of knowledge on Takotsubo syndrome: a position statement from the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2016;18(1):8-2).</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Lyon</surname>
              <given-names>AR</given-names>
            </name>
            <name>
              <surname>Bossone</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Schneider</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Sechtem</surname>
              <given-names>U</given-names>
            </name>
            <name>
              <surname>Citro</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Underwood</surname>
              <given-names>SR</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Current state of knowledge on Takotsubo syndrome: a position statement from the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology</article-title>
          <source>Eur J Heart Fail</source>
          <year>2016</year>
          <volume>18</volume>
          <issue>1</issue>
          <fpage>8</fpage>
          <lpage>2</lpage>
        </element-citation>
      </ref>
      <ref id="B4">
        <label>4</label>
        <mixed-citation>4. Johnson TW, R&#228;ber L, Mario C, Bourantas C, Jia H, Mattesini A, et al. Clinical Use of Intracoronary Imaging. Part 2: Acute Coronary Syndromes, Ambiguous Coronary Angiography Findings, and Guiding Interventional Decision-Making: An Expert Consensus Document of the European Association of Percutaneous Cardiovascular Interventions. Eur Heart J. 2019;40(31):2566-84.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Johnson</surname>
              <given-names>TW</given-names>
            </name>
            <name>
              <surname>R&#228;ber</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Mario</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Bourantas</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Jia</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Mattesini</surname>
              <given-names>A</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Clinical Use of Intracoronary Imaging. Part 2: Acute Coronary Syndromes, Ambiguous Coronary Angiography Findings, and Guiding Interventional Decision-Making: An Expert Consensus Document of the European Association of Percutaneous Cardiovascular Interventions</article-title>
          <source>Eur Heart J</source>
          <year>2019</year>
          <volume>40</volume>
          <issue>31</issue>
          <fpage>2566</fpage>
          <lpage>2584</lpage>
        </element-citation>
      </ref>
      <ref id="B5">
        <label>5</label>
        <mixed-citation>5. Ghadri JR, Wittstein IS, Prasad A, Sharkey S, Dote K, Akashi YJ, et al. International Expert Consensus Document on Takotsubo Syndrome (Part I): clinical characteristics, diagnostic criteria, and pathophysiology. Eur Heart J. 2018;39(22):2032-46.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ghadri</surname>
              <given-names>JR</given-names>
            </name>
            <name>
              <surname>Wittstein</surname>
              <given-names>IS</given-names>
            </name>
            <name>
              <surname>Prasad</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Sharkey</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Dote</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Akashi</surname>
              <given-names>YJ</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>International Expert Consensus Document on Takotsubo Syndrome (Part I): clinical characteristics, diagnostic criteria, and pathophysiology</article-title>
          <source>Eur Heart J</source>
          <year>2018</year>
          <volume>39</volume>
          <issue>22</issue>
          <fpage>2032</fpage>
          <lpage>2046</lpage>
        </element-citation>
      </ref>
      <ref id="B6">
        <label>6</label>
        <mixed-citation>6. Bratis K. Cardiac magnetic resonance in Takotsubo Syndrome. Eur Cardiol. 2017;12(1):58-62.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bratis</surname>
              <given-names>K</given-names>
            </name>
          </person-group>
          <article-title>Cardiac magnetic resonance in Takotsubo Syndrome</article-title>
          <source>Eur Cardiol</source>
          <year>2017</year>
          <volume>12</volume>
          <issue>1</issue>
          <fpage>58</fpage>
          <lpage>62</lpage>
        </element-citation>
      </ref>
    </ref-list>
    <fn-group>
      <fn fn-type="other">
        <p>
          <italic>Minieditorial referente ao artigo: Registro Multic&#234;ntrico de Takotsubo (REMUTA) &#8211; Aspectos Cl&#237;nicos, Desfechos Intra-Hospitalares e Mortalidade a Longo Prazo</italic>
        </p>
      </fn>
    </fn-group>
  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Short Editorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Takotsubo Syndrome, Does it Exist as a Specific Disease?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-6718-8456</contrib-id>
          <name>
            <surname>Caramelli</surname>
            <given-names>Bruno</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1001">
        <label>1</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Universidade de S&#227;o Paulo &#8211; Instituto do Cora&#231;&#227;o (InCor), S&#227;o Paulo, SP &#8211; Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c01001">Mailing Address: Bruno Caramelli &#8226; Universidade de S&#227;o Paulo &#8211; Instituto do Cora&#231;&#227;o (InCor) - Av. Dr. Eneas C. de Aguiar, 44. Postal Code 05403-000, S&#227;o Paulo, SP &#8211; Brazil. E-mail: bcaramel@usp.br, brunoc@cardiol.br</corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <kwd>Takotsubo Cardiomyopathy</kwd>
        <kwd>Ventricular Dysfunction</kwd>
        <kwd>Coronary Artery Disease</kwd>
        <kwd>Diagnosis,Differencial</kwd>
        <kwd>Diagnostic,Imaging</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>The name syndrome combines two Greek roots to describe a condition gathering a group of signs and symptoms existing together in patients. It seems that Avicenna first used it in his 1025 publication &#8220;The Canon of Medicine&#8221;.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> In genetics, the use of the name syndrome generally assumes that the underlying cause of the disease is known. On the other hand, in medicine, syndrome refers to conditions both with a known and unknown cause.</p>
      <p>Historically, associated signs and symptoms found to be of improbable correlation were eventually known to have an underlying cause responsible for all of them. Even after the cause is unraveled, the original word remains, sometimes with the name of the first describer, and this is probably the reason for the existence nowadays of syndromes with identified and unidentified causes.</p>
      <p>In this number, <italic>Arquivos Brasileiros de Cardiologia</italic> publishes the article entitled Takotsubo Multicenter Registry (REMUTA) - Clinical aspects, in-hospital outcomes, and long-term mortality.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> The Takotsubo syndrome was reported initially by Sato et al., in 1990, in Japan, describing 16 cases that shared well-known signs and symptoms: typical chest pain following a stressful event and &#8220;angiographically normal&#8221; coronary arteries.</p>
      <p>The Takotsubo Multicenter Registry (REMUTA) adopted the diagnostic criteria from the task force on Takotsubo syndrome of the Heart Failure Association of the European Society of Cardiology, published in 2016.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> According to these criteria, if the culprit coronary lesion is identified, the diagnosis of acute coronary syndrome is established, and Takotsubo syndrome is discarded. In the REMUTA registry, all patients performed coronary angiography, and 24.2% of them showed non-obstructive coronary artery disease, defined by the authors as less than 50% obstructions. The remaining 75.8% had, according to the authors, &#8220;angiographically normal&#8221; coronary arteries. However, there is no reference to the absence of a culprit coronary lesion in the patients studied, a necessary criterion for the diagnosis of Takotsubo syndrome, as stated in the first 2016 consensus, adopted by the REMUTA study.</p>
      <p>Above, the expression &#8220;angiographically normal&#8221; has quotes, on purpose, for one reason: the definition of angiographically normal coronary arteries is challenging to establish. There are limitations related to the resolution of imaging methods and the well-known concept that even subtle atherosclerotic plaques can trigger coronary thrombosis. Moreover, endothelial dysfunction affecting epicardial coronary arteries or its endocardial ramifications can be responsible for the development of acute coronary syndromes (ACS). Indeed, an International consensus about intracoronary imaging, published in 2019, states that the culprit lesion cannot be identified in 4&#8211;10% of the patients with ST-elevation ACS and in &gt;30% of patients non-ST-elevation.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> Considering all these caveats, even after modifications, the angiographic definition for Takotsubo syndrome does not offer a confident bedside criterion for clinical practice. Maybe for that reason, in 2018, the original definition of Takotsubo syndrome, suggested by Sato et al. was modified again, and the new consensus stated that significant coronary artery disease is not anymore, a contradiction for the diagnosis of Takotsubo syndrome.<sup><xref ref-type="bibr" rid="B5">5</xref></sup></p>
      <p>In medicine, it is of paramount importance to have health conditions with clear definitions for differential diagnosis, risk stratification, and as reference for future studies in clinical research. This principle paved the way for the establishment of the now central concepts of ST-elevation and non-ST-elevation acute coronary syndromes, for example. At the bedside, modern cardiologists know how to stratify risk and give adequate treatment for both conditions. This is not the case for Takotsubo syndrome that cannot be undoubtedly distinguishable from acute coronary syndromes. As can be seen in <xref ref-type="table" rid="t1001">Table 1</xref> , except for the increased prevalence in postmenopausal women, all other criteria are present in both syndromes, and the differences are based on subjective opinions taken in front of the patient. In the absence of objective criteria, differential diagnosis is challenging, and the patients could be misdiagnosed. Despite considering very important to have a National Registry of a specific disease (and I congratulate the authors for that effort), the reader cannot exclude the possibility that some patients in REMUTA had the diagnosis of ACS instead of Takotsubo Syndrome.</p>
      <p>
        <table-wrap id="t1001">
          <label>Table 1</label>
          <caption>
            <title>&#8211; Diagnostic criteria comparison chart between Takotsubo and Acute coronary syndromes</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="33%">
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Diagnostic criteria</th>
                <th>Takotsubo</th>
                <th>Acute coronary syndromes</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>Transient left ventricular dysfunction</td>
                <td align="center">+++</td>
                <td align="center">+</td>
              </tr>
              <tr>
                <td>Emotional/physical trigger</td>
                <td align="center">++</td>
                <td align="center">+</td>
              </tr>
              <tr>
                <td>Neurological disorders as a trigger</td>
                <td align="center">++</td>
                <td align="center">+</td>
              </tr>
              <tr>
                <td>New ECG abnormalities</td>
                <td align="center">++</td>
                <td align="center">+++</td>
              </tr>
              <tr>
                <td>Elevated cardiac biomarkers</td>
                <td align="center">+</td>
                <td align="center">+++</td>
              </tr>
              <tr>
                <td>Discard infection myocarditis</td>
                <td align="center">+</td>
                <td align="center">+</td>
              </tr>
              <tr>
                <td>More frequent in postmenopausal women</td>
                <td align="center">+</td>
                <td align="center">-</td>
              </tr>
              <tr>
                <td>Significant coronary artery disease</td>
                <td align="center">+</td>
                <td align="center">+++</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
      </p>
      <p>In summary, the correct diagnosis of Taktsubo syndrome often remains elusive. Conversely, recent data showed that magnetic resonance has a promising role in Takotsubo syndrome and could represent, in the future, the cornerstone for the differential diagnosis.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> Acute coronary syndromes represent today a big and important group of heart diseases, each one with specific characteristics and treatment. Takotsubo syndrome, on the contrary, still lacks a definitive identity. Is it a specific, independent disease or a peculiar presentation of an acute coronary syndrome? As in the Hebrew version of the story of Jonah in the Bible, Takotsubo must swim faster, get stronger and grow; otherwise, it will be swallowed by the giant fish.</p>
      <p>
        <fig id="f01001">
          <label>Figure 1</label>
          <caption>
            <title>&#8211; As in the Hebrew version of the story of Jonah in the Bible, Takotsubo must swim faster, get stronger and grow; otherwise, it will be swallowed by the giant fish. Art by Piero de Souza Dias Caramellli.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-115-02-0217-00470-gf01-en.tif"/></fig>
      </p>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other">
          <p>
            <italic>Short Editorial related to the article: Takotsubo Multicenter Registry (REMUTA) &#8211; Clinical Aspects, In-Hospital Outcomes, and Long-Term Mortality</italic>
          </p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
