<!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 pub-id-type="publisher-id" specific-use="scielo-v3">BDxVZBJLcCyX4JFGq5RwdTH</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2020000300484</article-id>
      <article-id pub-id-type="publisher-id">abc.20200080</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20200080</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>S&#237;ndrome de Takotsubo: Uma Doen&#231;a Recorrente?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-9323-8805</contrib-id>
          <name>
            <surname>Fernandes</surname>
            <given-names>F&#225;bio</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Montera</surname>
            <given-names>Marcelo Westmoreland</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgdiv1">Instituto do Cora&#231;&#227;o</institution>
        <institution content-type="orgname">Incor HC FMUSP</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Instituto do Cora&#231;&#227;o - Incor HC FMUSP, S&#227;o Paulo, SP - Brasil</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgname">Hospital Pr&#243;-Card&#237;aco</institution>
        <addr-line>
          <named-content content-type="city">Rio de Janeiro</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Hospital Pr&#243;-Card&#237;aco, Rio de Janeiro, RJ &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c01"> Correspond&#234;ncia: F&#225;bio Fernandes &#8226; Universidade de S&#227;o Paulo Faculdade de Medicina Hospital das Cl&#237;nicas Instituto do Cora&#231;&#227;o - Av. Dr. Eneas C. Aguiar, 44. CEP 05403-000, S&#227;o Paulo, SP &#8211; Brasil E-mail: <email>fabio.fernandes@incor.usp.br</email>
				</corresp>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>06</day>
        <month>04</month>
        <year>2020</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <season>May-Jun</season>
        <year>2020</year>
      </pub-date>
      <volume>114</volume>
      <issue>3</issue>
      <fpage>484</fpage>
      <lpage>485</lpage>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
        </license>
      </permissions>
      <kwd-group xml:lang="pt">
        <kwd>Cardiomiopatia de Takotsubo/diagn&#243;stico</kwd>
        <kwd>Fatores Et&#225;rios</kwd>
        <kwd>Cardiomiopatia de Takotsubo/etiologia</kwd>
        <kwd>Biomarcadores/sangue</kwd>
        <kwd>Catecolaminas/sangue</kwd>
        <kwd>Estrog&#234;nios/sangue</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="12"/>
        <page-count count="2"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>V&#225;rios termos (como S&#237;ndrome do Cora&#231;&#227;o Feliz, S&#237;ndrome do Cora&#231;&#227;o Partido e Cardiomiopatia de Takotsubo) t&#234;m sido utilizados para se referir &#224; S&#237;ndrome de Takotsubo (STT), definida recentemente. O primeiro caso de STT foi descrito no Jap&#227;o (Hiroshima City Hospital) em 1983 e um relato de cinco casos foi publicado em um livro de medicina japon&#234;s em 1990.<sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
    <p>Entretanto, em contraste com outras cardiomiopatias que geralmente n&#227;o s&#227;o transit&#243;rias por natureza, a STT &#233; caracterizada por uma anormalidade tempor&#225;ria do movimento da parede do VE na aus&#234;ncia de feocromocitoma, miocardite e compartilha caracter&#237;sticas comuns com sintomas semelhantes na apresenta&#231;&#227;o da s&#237;ndrome coron&#225;ria aguda (SCA), anormalidades no ECG, biomarcadores card&#237;acos elevados, bem como uma mortalidade hospitalar compar&#225;vel com infarto do mioc&#225;rdio com supradesnivelamento do segmento ST (IAMCST) e sem supradesnivelamento do segmento ST (IAMSST), especificamente em termos de um forma microvascular da SCA.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> A Sociedade Europeia de Cardiologia (ESC) tamb&#233;m estabeleceu o Crit&#233;rio Internacional de Diagn&#243;stico Takotsubo ( <italic>InterTAK Diagnostic Criteria</italic> ), que implementa um algoritmo de diagn&#243;stico e atribui uma pontua&#231;&#227;o &#224; STT.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
    <p>Como os sintomas t&#237;picos de Takotsubo s&#227;o o s&#250;bito aparecimento de dor tor&#225;cica, falta de ar ou colapso, esses pacientes acreditam inicialmente que est&#227;o apresentando uma s&#237;ndrome coron&#225;ria aguda. Aproximadamente 1% a 3% de todos os pacientes que apresentam sintomas consistentes com SCA e s&#227;o submetidos a angiografia coron&#225;ria, s&#227;o identificados como tendo STT.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
    <p>O alto n&#237;vel de catecolamina parece ser devido &#224; hiperativa&#231;&#227;o do sistema hipot&#225;lamo-hip&#243;fise-adrenal em resposta a um gatilho ex&#243;geno, que nem sempre &#233; facilmente reconhecido. Esses achados sugerem uma potencial intera&#231;&#227;o cora&#231;&#227;o-c&#233;rebro na fisiopatologia da STT, o papel do elo entre o cora&#231;&#227;o e o c&#233;rebro e o fator desencadeante e o g&#234;nero, e as raz&#245;es pelas quais essa s&#237;ndrome apresenta fen&#243;tipos diferentes e, &#224;s vezes, apresenta recorr&#234;ncia.<sup><xref ref-type="bibr" rid="B5">5</xref></sup></p>
    <p>No in&#237;cio dos estudos, uma caracter&#237;stica fundamental da s&#237;ndrome de Takotsubo &#233; a recupera&#231;&#227;o espont&#226;nea da fra&#231;&#227;o de eje&#231;&#227;o do VE, que retorna ao normal ou quase normal em quase todos os pacientes em um per&#237;odo vari&#225;vel de tempo (dias a semanas).<sup><xref ref-type="bibr" rid="B6">6</xref></sup></p>
    <p>Entretanto, a STT pode apresentar recorr&#234;ncia, com uma taxa de recidiva estimada em 1,8% por paciente ao ano.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> Como a recorr&#234;ncia n&#227;o &#233; frequente, isso impediu an&#225;lises adicionais de preditores e desfechos. A recorr&#234;ncia da STT &#233; definida como novas anormalidades do movimento da parede na aus&#234;ncia de doen&#231;a coronariana obstrutiva ap&#243;s a recupera&#231;&#227;o dos eventos-&#237;ndice da STT.<sup><xref ref-type="bibr" rid="B8">8</xref></sup></p>
    <p>O presente estudo publicado nos Arquivos Brasileiros de Cardiologia tem como objetivo analisar os principais fatores associados &#224; recorr&#234;ncia da s&#237;ndrome de Takotsubo. A taxa de recorr&#234;ncia global, considerando os estudos selecionados, foi de 3,8% em um tempo de seguimento que variou de 5 a 17 anos. Sexo feminino, tempo desde o primeiro epis&#243;dio da s&#237;ndrome, baixo IMC e obstru&#231;&#227;o m&#233;dia-ventricular foram relatados como poss&#237;veis preditores de recorr&#234;ncia da STT.<sup><xref ref-type="bibr" rid="B9">9</xref></sup></p>
    <p>H&#225; um reconhecimento crescente das diferen&#231;as de g&#234;nero na apresenta&#231;&#227;o, gatilhos, gravidade e complica&#231;&#245;es da STT. A literatura atual mostra uma predomin&#226;ncia feminina no n&#250;mero de pacientes com STT (propor&#231;&#227;o de mulheres para homens 9:1).<sup><xref ref-type="bibr" rid="B7">7</xref></sup> V&#225;rias explica&#231;&#245;es t&#234;m sido oferecidas, incluindo fatores como defici&#234;ncia de estrog&#234;nio, gatilhos subjacentes e uma resposta do sistema nervoso aut&#244;nomo aumentada.<sup><xref ref-type="bibr" rid="B6">6</xref> , <xref ref-type="bibr" rid="B7">7</xref></sup></p>
    <p>Em uma revis&#227;o sistem&#225;tica do progn&#243;stico em longo prazo e preditores de desfechos na S&#237;ndrome de Takotsubo, de 54 estudos que inclu&#237;ram um total de 4.679 pacientes, durante um seguimento m&#233;dio de 28 meses (intervalo interquartil: 23 a 34 meses), a taxa anual de mortalidade total foi de 3,5%, com uma taxa de recorr&#234;ncia anual de 1,0%. Uma an&#225;lise de meta-regress&#227;o mostrou que a mortalidade total em longo prazo em cada estudo foi significativamente associada &#224; idade mais avan&#231;ada (p = 0,05), estressor f&#237;sico (p = 0,0001) e &#224; forma at&#237;pica de balonamento da STT (p = 0,009).</p>
    <p>Os dist&#250;rbios neurol&#243;gicos (taxa de risco: 1,76; p=0,048) e os transtornos psiqui&#225;tricos (taxa de risco: 1,77; p=0,033) emergiram como preditores independentes de recorr&#234;ncia. Esses achados sugerem que a STT precisa de seguimento rigoroso, devido &#224; possibilidade de eventos adversos graves em longo prazo.<sup><xref ref-type="bibr" rid="B10">10</xref> , <xref ref-type="bibr" rid="B11">11</xref></sup></p>
    <p>A cardiomiopatia de Takotsubo tem 4 variantes anat&#244;micas principais e uma categoria de outras variantes raras: variante apical, t&#237;pica ou cl&#225;ssica, variante m&#233;dia-ventricular, variante basal, reversa ou invertida e a variante focal. A variante cl&#225;ssica e mais frequente da cardiomiopatia de Takotsubo geralmente afeta o &#225;pice do ventr&#237;culo esquerdo. Entretanto, v&#225;rios casos descreveram uma variante at&#237;pica.<sup><xref ref-type="bibr" rid="B12">12</xref></sup> Acredita-se que as distribui&#231;&#245;es relativas dos adrenoceptores beta-2 determinem as diferentes variantes anat&#244;micas. Um padr&#227;o vari&#225;vel da STT na recidiva &#233; comum em at&#233; 20% dos casos de recorr&#234;ncia.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> Hipocinesia m&#233;dia-ventricular esquerda com hipercontratilidade basal e apical &#233; relatada em 14,6% dos pacientes no Registro Internacional de Takotsubo.</p>
    <p>Recentemente, o registro multic&#234;ntrico GEIST ( <italic>German Italian Stress Cardiomyopathy</italic> ) incluiu 749 pacientes consecutivos com STT, inclu&#237;dos em 9 centros. No geral, a recorr&#234;ncia da STT foi documentada em 30 pacientes (4%), com mediana de seguimento de 830 dias. Fatores de risco cardiovasculares, como hipertens&#227;o arterial, foram significativamente maiores no grupo de recorr&#234;ncia. Curiosamente, em 14 pacientes (46%), a STT foi desencadeada por um novo estressor em compara&#231;&#227;o com o primeiro evento de STT (9 pacientes experimentaram um gatilho emocional e 5 pacientes experimentaram um gatilho f&#237;sico) e at&#233; 2 recorr&#234;ncias de STT foram documentadas em 6% dos casos.<sup><xref ref-type="bibr" rid="B10">10</xref></sup></p>
    <p>Ainda existem muitas perguntas sem resposta sobre essa s&#237;ndrome complexa. Curiosamente, nesta revis&#227;o, o uso de betabloqueadores ou outros medicamentos para insufici&#234;ncia card&#237;aca n&#227;o demonstrou reduzir a chance de recorr&#234;ncia. Kato et al.,<sup><xref ref-type="bibr" rid="B11">11</xref></sup> observaram que 59,6% dos pacientes estavam em terapia regular com betabloqueadores na admiss&#227;o relacionada &#224; recorr&#234;ncia de STT, a maioria dos quais eram compostos seletivos beta 1 em 84,6%, sugerindo que antagonistas seletivos beta 1 podem n&#227;o impedir a recorr&#234;ncia de STT e um tratamento ideal ainda precisa ser determinado.<sup><xref ref-type="bibr" rid="B11">11</xref></sup></p>
  </body>
  <back>
    <ref-list>
      <title>Refer&#234;ncias</title>
      <ref id="B1">
        <label>1</label>
        <mixed-citation>1. Sato H. Tako-tsubo-like left ventricular dysfunction due to multivessel coronary spasm. In: Kodama K., Haze K., Hori M., editors. Clinical Aspect of Myocardial Injury: From Ischemia to Heart Failure. Tokyo (Japan): Kagakuhyoronsha Publishing Co; 1990. pp. 56&#8211;64.</mixed-citation>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Sato</surname>
              <given-names>H</given-names>
            </name>
          </person-group>
          <chapter-title>Tako-tsubo-like left ventricular dysfunction due to multivessel coronary spasm</chapter-title>
          <person-group person-group-type="editor">
            <name>
              <surname>Kodama</surname>
              <given-names>K.</given-names>
            </name>
            <name>
              <surname>Haze</surname>
              <given-names>K.</given-names>
            </name>
            <name>
              <surname>Hori</surname>
              <given-names>M.</given-names>
            </name>
            <role>editors</role>
          </person-group>
          <source>Clinical Aspect of Myocardial Injury: From Ischemia to Heart Failure</source>
          <publisher-loc>Tokyo (Japan)</publisher-loc>
          <publisher-name>Kagakuhyoronsha Publishing Co</publisher-name>
          <year>1990</year>
          <fpage>56</fpage>
          <lpage>64</lpage>
        </element-citation>
      </ref>
      <ref id="B2">
        <label>2</label>
        <mixed-citation>2. Prasad A., Lerman A., Rihal C. S. Apical ballooning syndrome (tako-tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction. Am Heart J. 2008;155(3):408&#8211;17.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Prasad</surname>
              <given-names>A.</given-names>
            </name>
            <name>
              <surname>Lerman</surname>
              <given-names>A.</given-names>
            </name>
            <name>
              <surname>Rihal</surname>
              <given-names>C. S.</given-names>
            </name>
          </person-group>
          <article-title>Apical ballooning syndrome (tako-tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction</article-title>
          <source>Am Heart J</source>
          <year>2008</year>
          <volume>155</volume>
          <issue>3</issue>
          <fpage>408</fpage>
          <lpage>417</lpage>
        </element-citation>
      </ref>
      <ref id="B3">
        <label>3</label>
        <mixed-citation>3. 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&#8211;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="B4">
        <label>4</label>
        <mixed-citation>4. Schneider B, Sechtem U. Influence of age and gender in Takotsubo syndrome. Heart Fail Clin. 2016;12(4):521&#8211;30.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Schneider</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Sechtem</surname>
              <given-names>U</given-names>
            </name>
          </person-group>
          <article-title>Influence of age and gender in Takotsubo syndrome</article-title>
          <source>Heart Fail Clin</source>
          <year>2016</year>
          <volume>12</volume>
          <issue>4</issue>
          <fpage>521</fpage>
          <lpage>530</lpage>
        </element-citation>
      </ref>
      <ref id="B5">
        <label>5</label>
        <mixed-citation>5. Pelliccia F, Kaski JC, Crea F, Camici PG. Pathophysiology of Takotsubo syndrome. Circulation 2017;135(24):2426&#8211;41.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Pelliccia</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Kaski</surname>
              <given-names>JC</given-names>
            </name>
            <name>
              <surname>Crea</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Camici</surname>
              <given-names>PG</given-names>
            </name>
          </person-group>
          <article-title>Pathophysiology of Takotsubo syndrome</article-title>
          <source>Circulation</source>
          <year>2017</year>
          <volume>135</volume>
          <issue>24</issue>
          <fpage>2426</fpage>
          <lpage>2441</lpage>
        </element-citation>
      </ref>
      <ref id="B6">
        <label>6</label>
        <mixed-citation>6. Dawson DK. Acute stress-induced (takotsubo) cardiomyopathy. Heart. 2018;104(2):96-102.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Dawson</surname>
              <given-names>DK</given-names>
            </name>
          </person-group>
          <article-title>Acute stress-induced (takotsubo) cardiomyopathy</article-title>
          <source>Heart</source>
          <year>2018</year>
          <volume>104</volume>
          <issue>2</issue>
          <fpage>96</fpage>
          <lpage>102</lpage>
        </element-citation>
      </ref>
      <ref id="B7">
        <label>7</label>
        <mixed-citation>7. Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu DR, Jaguszewski M, et al. Clinical features and outcomes of takotsubo (stress) cardiomyopathy. N Engl J Med 2015;373(10):929&#8211;38.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Templin</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Ghadri</surname>
              <given-names>JR</given-names>
            </name>
            <name>
              <surname>Diekmann</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Napp</surname>
              <given-names>LC</given-names>
            </name>
            <name>
              <surname>Bataiosu</surname>
              <given-names>DR</given-names>
            </name>
            <name>
              <surname>Jaguszewski</surname>
              <given-names>M</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Clinical features and outcomes of takotsubo (stress) cardiomyopathy</article-title>
          <source>N Engl J Med</source>
          <year>2015</year>
          <volume>373</volume>
          <issue>10</issue>
          <fpage>929</fpage>
          <lpage>938</lpage>
        </element-citation>
      </ref>
      <ref id="B8">
        <label>8</label>
        <mixed-citation>8. El-Battrawy I, Santoro F, Stiermaier T, M&#246;ller C, Guastafierro F, Novo G, et al. Incidence and Clinical Impact of Recurrent Takotsubo Syndrome: Results From the GEIST Registry.J Am Heart Assoc.2019;8(9):e010753.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>El-Battrawy</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Santoro</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Stiermaier</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>M&#246;ller</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Guastafierro</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Novo</surname>
              <given-names>G</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Incidence and Clinical Impact of Recurrent Takotsubo Syndrome: Results From the GEIST Registry</article-title>
          <source>J Am Heart Assoc</source>
          <year>2019</year>
          <volume>8</volume>
          <issue>9</issue>
          <elocation-id>e010753</elocation-id>
        </element-citation>
      </ref>
      <ref id="B9">
        <label>9</label>
        <mixed-citation>9. Campos FAD, Ritt LEF, Costa JPS, Margarida Cruz CM, Feitosa-Filho GS, Oliveira QB et al. Factors Associated with Recurrence in Takotsubo Syndrome: A Systematic Review. Arq Bras Cardiol. 2020; 114(3):477-483.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Campos</surname>
              <given-names>FAD</given-names>
            </name>
            <name>
              <surname>Ritt</surname>
              <given-names>LEF</given-names>
            </name>
            <name>
              <surname>Costa</surname>
              <given-names>JPS</given-names>
            </name>
            <name>
              <surname>Margarida Cruz</surname>
              <given-names>CM</given-names>
            </name>
            <name>
              <surname>Feitosa-Filho</surname>
              <given-names>GS</given-names>
            </name>
            <name>
              <surname>Oliveira</surname>
              <given-names>QB</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Factors Associated with Recurrence in Takotsubo Syndrome: A Systematic Review</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2020</year>
          <volume>114</volume>
          <issue>3</issue>
          <fpage>477</fpage>
          <lpage>483</lpage>
        </element-citation>
      </ref>
      <ref id="B10">
        <label>10</label>
        <mixed-citation>10. Pelica F, Pasceri V, Patti G, Tanzilli G, Speciale G, Gaudio C, et al. Long-Term Prognosis and Outcome Predictors in Takotsubo Syndrome: A Systematic Review and Meta-Regression Study. JACC Heart Fail. 2019;7(2):143-54.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Pelica</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Pasceri</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Patti</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Tanzilli</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Speciale</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Gaudio</surname>
              <given-names>C</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Long-Term Prognosis and Outcome Predictors in Takotsubo Syndrome: A Systematic Review and Meta-Regression Study</article-title>
          <source>JACC Heart Fail</source>
          <year>2019</year>
          <volume>7</volume>
          <issue>2</issue>
          <fpage>143</fpage>
          <lpage>154</lpage>
        </element-citation>
      </ref>
      <ref id="B11">
        <label>11</label>
        <mixed-citation>11. Kato K, Di Vece D, Cammann VL, Micek J, Szawan KA, Bacchi B, et al. InterTAK Collaborators. Takotsubo Recurrence: Morphological Types and Triggers and Identification of Risk Factors. J Am Coll Cardiol. 2019;73(8):982-4.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Kato</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Di Vece</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Cammann</surname>
              <given-names>VL</given-names>
            </name>
            <name>
              <surname>Micek</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Szawan</surname>
              <given-names>KA</given-names>
            </name>
            <name>
              <surname>Bacchi</surname>
              <given-names>B</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>InterTAK Collaborators. Takotsubo Recurrence: Morphological Types and Triggers and Identification of Risk Factors</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2019</year>
          <volume>73</volume>
          <issue>8</issue>
          <fpage>982</fpage>
          <lpage>984</lpage>
        </element-citation>
      </ref>
      <ref id="B12">
        <label>12</label>
        <mixed-citation>12. Rashed A, Shokr M, Subahi A, Siddiqui F, Alkatib A, Afonso L. Reverse Takotsubo Cardiomyopathy in a Patient With Prior Apical Takotsubo Cardiomyopathy: Challenging the Beta Receptor Gradient Theory. Ochsner J. 2019;19(3):256-9.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Rashed</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Shokr</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Subahi</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Siddiqui</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Alkatib</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Afonso</surname>
              <given-names>L</given-names>
            </name>
          </person-group>
          <article-title>Reverse Takotsubo Cardiomyopathy in a Patient With Prior Apical Takotsubo Cardiomyopathy: Challenging the Beta Receptor Gradient Theory</article-title>
          <source>Ochsner J</source>
          <year>2019</year>
          <volume>19</volume>
          <issue>3</issue>
          <fpage>256</fpage>
          <lpage>259</lpage>
        </element-citation>
      </ref>
    </ref-list>
    <fn-group>
      <fn fn-type="other">
        <p>Minieditorial referente ao artigo: Fatores Associados &#224; Recorr&#234;ncia na S&#237;ndrome de Takotsubo: Uma Revis&#227;o Sistem&#225;tica</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: A Recurrent Disease?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-9323-8805</contrib-id>
          <name>
            <surname>Fernandes</surname>
            <given-names>F&#225;bio</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Montera</surname>
            <given-names>Marcelo Westmoreland</given-names>
          </name>
          <xref ref-type="aff" rid="aff2001">
            <sup>2</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1001">
        <label>1</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Instituto do Cora&#231;&#227;o - Incor HC FMUSP, S&#227;o Paulo, SP - Brazil</institution>
      </aff>
      <aff id="aff2001">
        <label>2</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Hospital Pr&#243;-Card&#237;aco, Rio de Janeiro, RJ &#8211; Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c01001">Mailing Address: F&#225;bio Fernandes &#8226; Universidade de S&#227;o Paulo Faculdade de Medicina Hospital das Cl&#237;nicas Instituto do Cora&#231;&#227;o - Av. Dr. Eneas C. Aguiar, 44. Postal Code 05403-000, S&#227;o Paulo, SP &#8211; Brazil E-mail: fabio.fernandes@incor.usp.br</corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <kwd>Takotsubo Cardiomyopathy/diagnosis</kwd>
        <kwd>Takotsubo Cardiomyopathy/etiology</kwd>
        <kwd>Biomarkers/blood</kwd>
        <kwd>Catecholamines/blood</kwd>
        <kwd>Estrogens/blood</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>Several terms (such as happy heart syndrome, broken heart syndrome, and takotsubo cardiomyopathy) have been used to refer to the recently defined Takotsubo Syndrome (TTS). The first case of TTS was described in Japan (Hiroshima City Hospital) in 1983 and a report of five cases was published in a Japanese medical textbook in 1990.<sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
      <p>However, in contrast to other cardiomyopathies that are usually not transient in nature, TTS is characterized by a temporary wall motion abnormality of the LV in the absence of pheochromocytoma, myocarditis and shares common features with acute coronary syndrome (ACS) similar symptoms at presentation, ECG abnormalities, elevated cardiac biomarkers, as well as a comparable in-hospital mortality with ST-segment elevation myocardial infarction (STEMI) and non-STEMI, specifically in terms of a microvascular ACS form.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> The European Society of Cardiology (ESC) has also established the International Takotsubo Diagnostic Criteria (InterTAK Diagnostic Criteria), which implement a diagnostic algorithm and assign a score to TTS.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
      <p>As the typical Takotsubo symptoms are sudden onset of chest pain, breathlessness or collapse, these patients have an initial belief that they are experiencing acute coronary syndrome. Approximately 1%&#8211;3% of all patients who present with symptoms consistent with ACS and undergo coronary angiography, are identified to have TTS.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
      <p>The high level of catecholamine seems to be due to hyperactivation of the hypothalamus-pituitary gland-adrenal system in response to an exogenous trigger, which is not always easily recognized. These findings suggested a potential heart-brain interaction in the pathophysiology of TTS, the role of the link between the heart and brain and that of triggering factors and gender, and the reasons why this syndrome displays different phenotypes and sometimes recurs.<sup><xref ref-type="bibr" rid="B5">5</xref></sup></p>
      <p>At the beginning of the studies, a fundamental characteristic of Takotsubo is the spontaneous recovery of the LV ejection fraction, which returns to normal or near normal in all patients over a variable period of time (days to weeks).<sup><xref ref-type="bibr" rid="B6">6</xref></sup></p>
      <p>However, TTS may recur, with a recurrence rate estimated to be 1.8% per-patient year.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> Because recurrence is not frequent, it precluded further analyses of predictors and outcomes. TTS recurrence is defined as new wall motion abnormalities in the absence of obstructive coronary disease after recovery of the index TTS events.<sup><xref ref-type="bibr" rid="B8">8</xref></sup></p>
      <p>In this study published in the Arquivos Brasileiros de Cardilogia aims to analyze the main factors associated with Takotsubo syndrome recurrence. The global recurrence rate, considering the selected studies, was 3.8% in a follow up that ranged from 5 to 17 years. Female gender, time from the first episode of the syndrome, low BMI and midventricular obstruction were reported as potential predictors of TTS recurrence.<sup><xref ref-type="bibr" rid="B9">9</xref></sup></p>
      <p>There is increasing recognition of gender differences in the presentation, triggers, severity, and complications of TTS. The current literature shows a female preponderance in the number of patients with TTS (female to male ratio 9:1).<sup><xref ref-type="bibr" rid="B7">7</xref></sup> Various explanations have been offered, including factors such as estrogen deficiency, underlying triggers, and a heightened autonomic nervous system response.<sup><xref ref-type="bibr" rid="B6">6</xref> , <xref ref-type="bibr" rid="B7">7</xref></sup></p>
      <p>In a systematic review and meta-regression of long-term prognosis and outcome predictors in Takotsubo Syndrome, of 54 studies that included a total of 4,679 patients, during a median follow-up of 28 months (interquartile range: 23 to 34 months), the annual rate of total mortality was 3.5% with an annual rate of recurrence of 1.0%. A meta-regression analysis showed that long-term total mortality in each study was significantly associated with older age (p = 0.05), physical stressor (p = 0.0001), and the atypical ballooning form of TTS (p = 0.009). Neurological disorders (hazard ratio: 1.76; p = 0.048) and psychiatric disorders (hazard ratio: 1.77; p = 0.033) emerged as independent predictors of recurrence. These findings suggest that TTS needs a strict follow-up, due to the possibility of severe adverse events over the long term.<sup><xref ref-type="bibr" rid="B10">10</xref> , <xref ref-type="bibr" rid="B11">11</xref></sup></p>
      <p>Takotsubo cardiomyopathy has 4 main anatomic variants and a category of other rare variants: Apical, typical, or classic variant, Midventricular variant, Basal, reverse, or inverted variant and the Focal variant. The classic and most frequent variant of Takotsubo cardiomyopathy usually affects the left ventricular apex. However, several cases have described an atypical variant.<sup><xref ref-type="bibr" rid="B12">12</xref></sup> Relative distributions of the beta-2 adrenoceptors are believed to determine the different anatomic variants. A variable TTS pattern at recurrence is common in up to 20% of recurrence cases.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> Mid-left ventricular hypokinesia with basal and apical hypercontractility is reported for 14.6% of patients in the International Takotsubo Registry.</p>
      <p>Recently, the multicenter GEIST (German Italian Stress Cardiomyopathy) Registry included 749 consecutive patients with TTS, enrolled from 9 centers. Overall, TTS recurrence was documented in 30 patients (4%) at a median follow-up of 830 days. Cardiovascular risk factors, such as arterial hypertension were significantly higher in the recurrence group. Interestingly, in 14 patients (46%), TTS was triggered by a new stressor compared with the first TTS event (9 patients experienced an emotional trigger, and 5 patients experienced a physical trigger) and up to 2 TTS recurrences were documented in 6% of cases.<sup><xref ref-type="bibr" rid="B10">10</xref></sup></p>
      <p>There remain many unanswered questions regarding this complex syndrome. Interestingly, in this review the use of betablockers or other heart failure medications was not proved to reduce the chance of recurrence. Kato et al.,<sup><xref ref-type="bibr" rid="B11">11</xref></sup> showed that 59.6% of patients were on regular betablocker therapy on admission related to TTS recurrence, most of which were beta 1-selective compounds in 84.6%, suggesting that beta 1-selective antagonists might not prevent TTS recurrence and an optimal treatment still needs to be determined.<sup><xref ref-type="bibr" rid="B11">11</xref></sup></p>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other">
          <p>Short editorial related to the article: Factors Associated with Recurrence in Takotsubo Syndrome: A Systematic Review</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
