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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id specific-use="scielo-v3" pub-id-type="publisher-id">6XCmgcyDBMSZzkjL9C38YQn</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2023000700211</article-id>
      <article-id pub-id-type="other">00211</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20230410</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>A V&#225;lvula Esquecida n&#227;o deve ser Abandonada: Impacto da Insufici&#234;ncia Tric&#250;spide nos Resultados Cl&#237;nicos ap&#243;s Implante de V&#225;lvula A&#243;rtica Transcateter</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-1133-0465</contrib-id>
          <name>
            <surname>Kanhouche</surname>
            <given-names>Gabriel</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-1273-1823</contrib-id>
          <name>
            <surname>Ribeiro</surname>
            <given-names>Henrique B.</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="orgdiv2">Hospital das Cl&#237;nicas</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina</institution>
        <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c01"> Correspond&#234;ncia: Henrique B. Ribeiro &#8226; Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo - Av. Dr. En&#233;as de Carvalho Aguiar, 44. CEP 05403-900, S&#227;o Paulo, SP - Brasil E-mail: <email>henrique.ribeiro@hc.fm.usp.br</email> </corresp>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>14</day>
        <month>08</month>
        <year>2023</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>07</month>
        <year>2023</year>
      </pub-date>
      <volume>120</volume>
      <issue>7</issue>
      <elocation-id>e20230410</elocation-id>
      <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>Estenose A&#243;rtica</kwd>
        <kwd>Regurgita&#231;&#227;o Tric&#250;spide</kwd>
        <kwd>Insufici&#234;ncia Tric&#250;spide</kwd>
        <kwd>Dano Card&#237;aco Extravalvar</kwd>
        <kwd>Implante Transcateter de V&#225;lvula A&#243;rtica</kwd>
        <kwd>TAVI</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="11"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>A estenose a&#243;rtica (EAo) grave &#233; uma doen&#231;a frequente e potencialmente grave se n&#227;o for tratada. Apesar da ampla ado&#231;&#227;o da substitui&#231;&#227;o cir&#250;rgica da v&#225;lvula a&#243;rtica (SAVR) e, mais recentemente, do implante transcateter da v&#225;lvula a&#243;rtica (TAVI), as taxas de mortalidade no seguimento de m&#233;dio e longo prazo permanecem relativamente altas, especialmente para pacientes de mais alto risco.<sup><xref ref-type="bibr" rid="B1">1</xref> , <xref ref-type="bibr" rid="B2">2</xref></sup> Da mesma forma, embora a TAVI transfemoral tenha se tornado a abordagem dominante para pacientes com idade &gt; 70 anos, permitindo uma redu&#231;&#227;o significativa nas taxas de mortalidade por todas as causas e card&#237;acas em compara&#231;&#227;o &#224; SAVR, o progn&#243;stico de determinados subgrupos de pacientes ainda est&#225; comprometido.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Portanto, estudos anteriores na &#225;rea de TAVI t&#234;m se concentrado em ajudar na estratifica&#231;&#227;o de risco desses pacientes. Por exemplo, G&#233;n&#233;reux et al.<sup><xref ref-type="bibr" rid="B3">3</xref> , <xref ref-type="bibr" rid="B4">4</xref></sup> demonstraram que a extens&#227;o do dano card&#237;aco entre pacientes com EAo submetidos ao TAVI pode desempenhar um papel importante. Assim, um impacto gradual em mortalidade no seguimento foi demonstrado quando os pacientes com EAo tamb&#233;m apresentavam comprometimento da c&#226;mara esquerda, com ou sem regurgita&#231;&#227;o mitral, seguida de hipertens&#227;o pulmonar, com ou sem insufici&#234;ncia tric&#250;spide (IT) e, finalmente, com disfun&#231;&#227;o do ventr&#237;culo direito.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> Vale ressaltar que os dois &#250;ltimos est&#225;gios (com IT moderada ou grave e disfun&#231;&#227;o do ventr&#237;culo direito) representam a maior taxa de mortalidade, chegando a 20% em 1 ano.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> Al&#233;m do grau de IT, h&#225; controv&#233;rsia sobre se as mudan&#231;as no grau IT no seguimento tamb&#233;m podem desempenhar um papel nos resultados cl&#237;nicos.</p>
    <p>Nesta edi&#231;&#227;o do jornal, Erbano et al.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> avaliaram a associa&#231;&#227;o entre IT e mortalidade em uma revis&#227;o sistem&#225;tica e metan&#225;lise de pacientes com EAo submetidos ao TAVI, tendo tamb&#233;m avaliado as mudan&#231;as na gravidade da IT p&#243;s-TAVI e sua rela&#231;&#227;o com a mortalidade a curto e m&#233;dio prazos. O desfecho prim&#225;rio foi definido como a incid&#234;ncia de mortalidade por todas as causas de acordo com os graus de IT pr&#233;-procedimento. Os desfechos secund&#225;rios inclu&#237;ram mortalidade card&#237;aca e hospitaliza&#231;&#227;o por insufici&#234;ncia card&#237;aca. Os autores inclu&#237;ram 24 estudos, com mais de 45.000 pacientes, cuja idade m&#233;dia foi de 81,7&#177;8,5 anos; 52% eram do sexo feminino, com m&#233;dia de escore de risco pelo Society of Thoracic Surgeons (STS) de 8,2&#177;6,0. Aproximadamente 22% dos pacientes apresentavam IT moderada ou grave no in&#237;cio do estudo. Ap&#243;s um acompanhamento m&#233;dio de 1,2 anos, a an&#225;lise agrupada de 14 estudos revelou que graus mais altos de IT foram associados a um pior progn&#243;stico. A IT grave foi associada a um aumento de 83% na mortalidade em compara&#231;&#227;o com IT leve no curto prazo e 56% no m&#233;dio prazo. Na an&#225;lise agrupada, a persist&#234;ncia de graus moderados/graves de IT, ap&#243;s um seguimento m&#233;dio de 21 meses p&#243;s-TAVI, tamb&#233;m foi associada a um aumento de 2 vezes na mortalidade por todas as causas.</p>
    <p>Estudos pr&#233;vios no campo TAVI ressaltaram o potencial impacto do dano card&#237;aco nos resultados cl&#237;nicos em pacientes com EAo submetidos a SAVR e TAVI.<sup><xref ref-type="bibr" rid="B5">5</xref> , <xref ref-type="bibr" rid="B6">6</xref></sup> Nesses estudos, a gravidade da IT e o envolvimento do ventr&#237;culo direito foram fatores-chave que determinaram maior mortalidade (~2,2 vezes em 2 anos de seguimento em TAVI e 1,6 vezes em 2 anos de seguimento em SAVR).<sup><xref ref-type="bibr" rid="B6">6</xref> , <xref ref-type="bibr" rid="B7">7</xref></sup> O presente estudo amplia ainda mais essas observa&#231;&#245;es, demonstrando um impacto nos desfechos cl&#237;nicos de curto e m&#233;dio prazo de acordo com a gravidade da IT ap&#243;s TAVI, mesmo ap&#243;s m&#250;ltiplos ajustes para fatores de confus&#227;o. A EAo grave causa sobrecarga de press&#227;o resultando em remodelamento card&#237;aco do ventr&#237;culo esquerdo, seguido de envolvimento das c&#226;maras card&#237;acas direitas em est&#225;gios avan&#231;ados.<sup><xref ref-type="bibr" rid="B8">8</xref> , <xref ref-type="bibr" rid="B9">9</xref></sup> Se a IT representa apenas um marcador substituto de uma doen&#231;a mais avan&#231;ada ou um fator de risco, ainda permanece incerto.</p>
    <p>Outro ponto importante nesta metan&#225;lise &#233; que a gravidade da IT melhorou em pelo menos um grau em ~40% dos pacientes. Pacientes sem melhora no grau da IT p&#243;s-procedimento apresentaram piores resultados e qualidade de vida.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Em outro estudo, Genereux et al. tamb&#233;m demonstraram que a progress&#227;o ou regress&#227;o do dano card&#237;aco extravalvar no seguimento de 1 ano p&#243;s-TAVI pode se associar ao progn&#243;stico.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Pacientes com piora do dano card&#237;aco ap&#243;s 1 ano tiveram 95% mais chance de mortalidade.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> O impacto significativo da gravidade da IT nos desfechos cl&#237;nicos pode estar relacionado a fatores cl&#237;nicos como fibrila&#231;&#227;o atrial, hipertens&#227;o pulmonar e disfun&#231;&#227;o do ventr&#237;culo direito. Por exemplo, Granot et al. demonstraram mortalidade 3,3 vezes maior ap&#243;s TAVI entre pacientes com gravidade de IT persistente e disfun&#231;&#227;o do ventr&#237;culo direito.<sup><xref ref-type="bibr" rid="B2">2</xref> , <xref ref-type="bibr" rid="B10">10</xref></sup></p>
    <p>Em conjunto, esses achados sugerem que o manejo precoce da EAo, antes que ocorra dano card&#237;aco extravalvar, pode melhorar o progn&#243;stico e reduzir a mortalidade. De fato, mesmo no tratamento de pacientes com EAo grave assintom&#225;tica, realizar interven&#231;&#227;o precoce com TAVI independentemente da condi&#231;&#227;o card&#237;aca (EARLY TAVR; ClinicalTrials.gov: NCT03042104) ou entre aqueles com sinais incipientes de descompensa&#231;&#227;o do ventr&#237;culo esquerdo, apesar da aus&#234;ncia de sintomas (EVOLVED; ClinicalTrials.gov: NCT03094143), tamb&#233;m poder&#227;o mostrar um impacto significativo nos resultados cl&#237;nicos em um futuro pr&#243;ximo. Enquanto isso, entre pacientes com doen&#231;a mais avan&#231;ada e maior gravidade da IT, a combina&#231;&#227;o de m&#250;ltiplas interven&#231;&#245;es transcateter tanto na valva a&#243;rtica quanto em outras valvas com doen&#231;a concomitante significativa (ou seja, mitral e tric&#250;spide) tamb&#233;m podem melhorar os resultados cl&#237;nicos.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> A presente meta-an&#225;lise nesta edi&#231;&#227;o, certamente esclareceu a import&#226;ncia da gravidade da IT em pacientes submetidos ao TAVI. Enfatiza a import&#226;ncia de um diagn&#243;stico imediato e um plano de tratamento bem elaborado para pacientes com EAo, incluindo v&#225;rias especialidades, tratamento cl&#237;nico otimizado e interven&#231;&#245;es adequadas e oportunas para melhorar os resultados cl&#237;nicos em um grupo t&#227;o complexo e heterog&#234;neo de pacientes.</p>
  </body>
  <back>
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    <fn-group>
      <fn fn-type="other">
        <p>
          <italic>Minieditorial referente ao artigo: Insufici&#234;ncia Tric&#250;spide e Mortalidade em Pacientes Submetidos &#224; Troca da Valva A&#243;rtica Transcateter: Uma Revis&#227;o Sistem&#225;tica e Metan&#225;lise</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>The Forgotten Valve is not to be Forgiven: Tricuspid Regurgitation Impact on Clinical Outcomes after Transcatheter Aortic Valve Implantation</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-1133-0465</contrib-id>
          <name>
            <surname>Kanhouche</surname>
            <given-names>Gabriel</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-1273-1823</contrib-id>
          <name>
            <surname>Ribeiro</surname>
            <given-names>Henrique B.</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">Brasil</country>
        <institution content-type="original">Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c01001">Mailing Address Henrique B. Ribeiro &#8226; Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo - Av. Dr. En&#233;as de Carvalho Aguiar, 44. Postal Code 05403-900, S&#227;o Paulo, SP - Brazil E-mail: henrique.ribeiro@hc.fm.usp.br</corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <kwd>Aortic Stenosis</kwd>
        <kwd>Tricuspid Regurgitation</kwd>
        <kwd>Extravalvular Cardiac Damage</kwd>
        <kwd>Transcatheter Aortic Valve Implantation</kwd>
        <kwd>TAVI</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>Severe aortic stenosis (AS) is a frequent and potentially severe disease if left untreated. Despite the widespread adoption of surgical aortic valve replacement (SAVR) and more recently transcatheter aortic valve implantation (TAVI), mortality rates in the mid- to long-term follow-up remain relatively high, especially for higher-risk patients.<sup><xref ref-type="bibr" rid="B1">1</xref> , <xref ref-type="bibr" rid="B2">2</xref></sup> Yet, transfemoral TAVI became the dominant approach for patients with age &gt; 70 years, enabling a significant reduction in the all-cause and cardiac mortality rates with respect to SAVR, even though the prognosis of a certain subgroup of patients is still jeopardized.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Therefore, prior studies in the TAVI field have focused on helping in risk stratifying such patients. For instance, Genereux et al.<sup><xref ref-type="bibr" rid="B3">3</xref> , <xref ref-type="bibr" rid="B4">4</xref></sup> have shown that the extent of cardiac damage among patients with AS undergoing TAVI could play an important role. Accordingly, a stepwise impact in the mortality at follow-up was demonstrated when patients with AS also had left chamber involvement, with or without mitral regurgitation, followed by pulmonary hypertension, with or without tricuspid regurgitation (TR), and finally with right ventricle dysfunction.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> Of note, the last two stages (with moderate or severe TR and right ventricle dysfunction) represent the highest mortality rate, up to 20% at 1 year.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> Apart from TR grade, there is controversy on whether the changes in TR grade in the follow-up might also affect the clinical outcomes.</p>
      <p>In this journal issue, Erbano et al.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> evaluated the association between TR and mortality in a systematic review and meta-analysis of patients with AS undergoing TAVI and further assessed the changes in TR severity post-TAVI and its relationship with short and mid-term mortality. The primary endpoint was defined as the incidence of all-cause mortality according to TR grade at baseline. Secondary endpoints included cardiac mortality and heart failure hospitalization. The authors included 24 studies and more than 45.000 patients, whose mean age was 81.7&#177;8.5 years; 52% were female, with a mean Society of Thoracic Surgeons (STS) score of 8.2&#177;6.0. Approximately 22% of patients had moderate or severe TR at baseline. After a mean follow-up of 1.2 years, pooled analysis of 14 studies revealed that higher grades of TR were associated with a worse prognosis. Severe TR was associated with an 83% increased mortality compared to no/mild TR in the short-term and 56% in the mid-term. In the pooled analysis, the persistence of moderate/severe TR grades, after a mean follow-up of 21 months post-TAVI, was also associated with a 2-fold increase in all-cause mortality.</p>
      <p>Prior studies in the TAVI field have underlined the potential impact of cardiac damage on clinical outcomes among patients with AS undergoing SAVR and TAVI.<sup><xref ref-type="bibr" rid="B5">5</xref> , <xref ref-type="bibr" rid="B6">6</xref></sup> In such studies, TR severity and right ventricle involvement were key factors determining greater mortality (~2.2-fold at 2 years follow-up in TAVI and 1.6-fold at 2 years follow-up for SAVR).<sup><xref ref-type="bibr" rid="B6">6</xref> , <xref ref-type="bibr" rid="B7">7</xref></sup> The present study extends these observations further, demonstrating both an impact in the short- and mid-term clinical outcomes according to TR severity after TAVI, even after multiple adjustments for confounders. Severe AS causes pressure overload resulting in cardiac remodeling of the left ventricle, followed by right cardiac chambers involvement in an advanced stage.<sup><xref ref-type="bibr" rid="B8">8</xref> , <xref ref-type="bibr" rid="B9">9</xref></sup> Whether TR represents only a surrogate marker of a more advanced disease or a risk factor remains uncertain.</p>
      <p>Another important point in this meta-analysis is that TR severity improved by at least one grade in ~40% of patients. Patients without improved TR severity post-procedure presented worse outcomes and quality of life.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> In another study, Genereux et al. also demonstrated that progression or regression of extravalvular cardiac damage after 1 year post-TAVI may associate with prognosis.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Patients with worsening cardiac damage after 1 year had a 95% more chance of mortality.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> The significant impact of TR severity on clinical outcomes might be related to clinical factors such as atrial fibrillation, pulmonary hypertension, and right ventricle dysfunction. For instance, Granot <italic>et al.</italic> demonstrated 3.3-fold increased mortality after TAVI among patients with persistent TR severity and right ventricle dysfunction.<sup><xref ref-type="bibr" rid="B2">2</xref> , <xref ref-type="bibr" rid="B10">10</xref></sup></p>
      <p>Collectively, these findings suggest that earlier management of AS, before extravalvular cardiac damage ensues, may improve prognosis and reduce mortality. Indeed, even in the treatment of patients with asymptomatic severe AS, performing an earlier intervention with TAVI irrespective of the cardiac condition (EARLY TAVR; ClinicalTrials.gov: NCT03042104) or among those with incipient signs of left ventricle decompensation, despite the absence of symptoms (EVOLVED trial; ClinicalTrials.gov: NCT03094143), might also show a noteworthy impact on the clinical outcomes in the near future. Meanwhile, among patients with more advanced disease and TR severity, the combination of multiple transcatheter interventions both in the aortic valve and other concomitant valve diseases (i.e., mitral and tricuspid) might also enhance clinical outcomes.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> The present meta-analysis in this issue has certainly shed some light on the importance of TR severity among patients undergoing TAVI. It emphasizes the importance of a prompt diagnostic and a well-elaborated treatment plan for patients with AS, including multiple specialties, optimal medical treatment, and proper, timely interventions to improve clinical outcomes in such a complex and heterogeneous group of patients.</p>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other">
          <p>
            <italic>Short Editorial related to the article: Tricuspid Regurgitation and Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis</italic>
          </p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
