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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">TTnvRFNxcJfBBPrwnyh6nPz</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2022000601016</article-id>
      <article-id pub-id-type="publisher-id">abc.20220353</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20220353</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Troponina &#8211; Use com Sabedoria. E como mais um Instrumento na Cl&#237;nica</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <contrib-id contrib-id-type="orcid">0000-0003-0570-4368</contrib-id>
          <name>
            <surname>Wang</surname>
            <given-names>Ricardo</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Figueiredo</surname>
            <given-names>Estev&#257;o Lanna</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <aff id="aff1">
          <label>1</label>
          <institution content-type="orgname">Universidade Federal e Minhas Gerais</institution>
          <institution content-type="orgdiv1">Instituto Orizonti Hospital das Cl&#237;nicas</institution>
          <addr-line>
            <named-content content-type="city">Belo Horizonte</named-content>
            <named-content content-type="state">MG</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Instituto Orizonti Hospital das Cl&#237;nicas da Universidade Federal e Minhas Gerais, Belo Horizonte, MG &#8211; Brasil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><bold>Correspond&#234;ncia: Ricardo Wang</bold> &#8226; Rua Jos&#233; Patroc&#237;nio Pontes, 1355. CEP <postal-code>30210-090</postal-code>, Belo Horizonte, MG &#8211; Brasil. E-mail: <email>rwang@terra.com.br</email></corresp>
      </author-notes>
      <pub-date publication-format="electronic" date-type="pub">
        <day>10</day>
        <month>06</month>
        <year>2022</year>
      </pub-date>
      <pub-date publication-format="electronic" date-type="collection">
        <year>2022</year>
      </pub-date>
      <volume>118</volume>
      <issue>6</issue>
      <fpage>1016</fpage>
      <lpage>1017</lpage>
      <permissions>
        <license license-type="open-access" xml:lang="en" xlink:href="https://creativecommons.org/licenses/by/4.0/">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License</license-p>
        </license>
      </permissions>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave</title>
        <kwd>Infarto do Mioc&#225;rdio</kwd>
        <kwd>Biomarcadores</kwd>
        <kwd>Troponina</kwd>
        <kwd>Mortalidade</kwd>
        <kwd>Epidemiologia</kwd>
        <kwd>Isquemia Mioc&#225;rdica</kwd>
        <kwd>Revasculariza&#231;&#227;o Mioc&#225;rdica</kwd>
        <kwd>S&#237;ndrome Coronariana Aguda</kwd>
        <kwd>Progn&#243;stico</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="6"/>
        <page-count count="2"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>O infarto agudo do mioc&#225;rdio (IAM) junto com a doen&#231;a coronariana cr&#244;nica est&#225;vel s&#227;o as principais causas de mortalidade no Brasil.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Em 2019 foi respons&#225;vel por mais de 170.000 &#243;bitos no Brasil. Dado &#224; sua gravidade, houve, na Cardiologia, grande empenho na melhoria constante das ferramentas para o diagn&#243;stico correto, na tentativa de evitar a libera&#231;&#227;o de pacientes com S&#237;ndrome Coronariana Aguda (SCA), e suas consequ&#234;ncias cl&#237;nicas e jur&#237;dicas. S&#227;o considerados pilares para o diagn&#243;stico, al&#233;m de uma boa anamnese com a caracteriza&#231;&#227;o do tipo da dor, as altera&#231;&#245;es eletrocardiogr&#225;ficas e os biomarcadores (principalmente a troponina).</p>
    <p>Os biomarcadores t&#234;m um papel importante no reconhecimento da SCA, e os algor&#237;tmicos de diagn&#243;stico foram se adaptando &#224; medida que evolu&#237;am. No in&#237;cio, eram marcadores inespec&#237;ficos (p.e.: desidrogenase l&#225;tica, transaminase oxac&#233;tica, creatinofosfoquinase total &#8211; CK). Depois evoluiram para um marcador um pouco mais espec&#237;fico (creatininofosfoquinase por&#231;&#227;o MB &#8211; e com ele seus dif&#237;ceis crit&#233;rios: p.e.: rela&#231;&#245;es CK total/MB). Finalmente, temos um marcador extremamente espec&#237;fico da inj&#250;riamioc&#225;rdica como a troponina. A evolu&#231;&#227;o dos biomarcadores permitiu a simplifica&#231;&#227;o dos protocolos de dor tor&#225;cica, e a redu&#231;&#227;o de alta inapropriada de pacientes com SCA.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> Devido &#224; alta sensibilidade e especificidade da troponina, no quarto consenso sobre a defini&#231;&#227;o universal de Infarto Mioc&#225;rdico, se chegou &#224; conclus&#227;o de que para estabelecer o diagn&#243;stico cl&#237;nico s&#227;o necess&#225;rios a eleva&#231;&#227;o acima do percentil 99 deste biomarcador, associado a evid&#234;ncia cl&#237;nica de isquemia mioc&#225;rdica.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Dado ao baixo corte da troponina, neste consenso h&#225; d&#250;vidas em rela&#231;&#227;o &#224; relev&#226;ncia cl&#237;nica.</p>
    <p>Nesta edi&#231;&#227;o dos Arquivos Brasileiros de Cardiologia, Tapas-Filho et al.,<sup><xref ref-type="bibr" rid="B4">4</xref></sup> comparam o n&#237;vel de corte percentil 99 versus o corte da bula do fabricante da troponina. Eles observaram que o valores utilizados de troponina elevados acima do percentil 99 pela 4<sup>a</sup> Defini&#231;&#227;o Universal de Infarto foram uteis em rela&#231;&#227;o ao progn&#243;stico, ou seja, foram capazes de prever o desfecho composto de &#243;bito e reinfarto em at&#233; 30 dias. Uma observa&#231;&#227;o adicional &#233; que n&#237;veis de troponina minimamente elevados possibilitaram estratificar melhor os pacientes e identificar aqueles com maior probabilidade de se beneficiarem da estrat&#233;gia invasiva precoce e de procedimentos de revasculariza&#231;&#227;o coron&#225;ria.</p>
    <p>Em rela&#231;&#227;o ao trabalho publicado, apesar de dar suporte &#224;s recomenda&#231;&#245;es, h&#225; algumas quest&#245;es a se analisar. Primeiramente, trata-se de um registro de um &#250;nico centro, com uma amostra limitada (494 pacientes), dentre os quais, os pacientes com troponina entre 0,034 e 0,12ng/dL foram somente 39. Segundo, observamos que a mortalidade dos grupos &#233; baixa (2,4% a 3,9%) no registro, o que pode ser explicado pela popula&#231;&#227;o de baixo risco (GRACE SCORE: 102 (trop &gt; 0,034-0,12ng/dL) x 120 (trop &gt;0,12 ng/dL)). Outra poss&#237;vel explica&#231;&#227;o para a baixa mortalidade mencionada pelos autores &#233; a alta taxa de estrat&#233;gia invasiva e revasculariza&#231;&#227;o coron&#225;ria precoce. Os n&#237;veis mais elevados de troponina apresentaram maior incid&#234;ncia de reinfarto (16,2% versus 4,8%), e ocorreram principalmente nos primeiros 15 dias. No estudo n&#227;o ficaram claras as causas desse aumento. Podemos especular: revasculariza&#231;&#227;o incompleta? Infarto relacionado a procedimento (IAM tipo IV ou V)? S&#227;o quest&#245;es a serem analisadas com cuidado.</p>
    <p>Al&#233;m da limita&#231;&#227;o quanto ao tamanho da amostra do estudo, outro ponto de aten&#231;&#227;o &#233; o per&#237;odo de seguimento. Quando comparamos com o registro SWEDEHEART (com mais de 48.000 pacientes inclu&#237;dos), e a an&#225;lise deste subgrupo (9.800 pacientes), acompanhado por dez anos, observou-se aumento dos eventos cardiovasculares nesta popula&#231;&#227;o, na ordem de 15,4%.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Isto refor&#231;a a import&#226;ncia de pequenos aumentos da troponina como marcador de progn&#243;stico a longo prazo.</p>
    <p>Se por um lado, abaixar o ponto de corte dos biomarcadores &#233; preditor de eventos, por outro lado h&#225; preocupa&#231;&#227;o na redu&#231;&#227;o da especificidade do teste, com aumento no n&#250;mero de falso positivos,<sup><xref ref-type="bibr" rid="B6">6</xref></sup> o que poderia levar a procedimentos desnecess&#225;rios, e ao aumento, por exemplo, de coronariografias sem les&#245;es coronarianas (os chamados &#8220;cates brancos&#8221;). O que pode estigmatizar o paciente e expor a complica&#231;&#245;es relacionados &#224; assist&#234;ncia. No registro de Tapas-Filho,<sup><xref ref-type="bibr" rid="B4">4</xref></sup> observamos que em pacientes com n&#237;veis mais baixos de troponina, 92% foram submetidos a coronariografia e a taxa de revasculariza&#231;&#227;o foi de &gt; 75% (semelhante ao grupo de troponina mais elevada). Mesmo assim, refor&#231;amos que em geral 25% dos pacientes poderiam n&#227;o ter sido submetidos a testes invasivos.</p>
    <p>Sob nosso ponto de vista, o momento &#233; de buscar marcadores, que evitem que pacientes sejam submetidos &#224; estrat&#233;gia invasiva desnecessariamente. Para termos a dimens&#227;o dos n&#250;meros, se considerarmos aproximadamente 110.000 revasculariza&#231;&#245;es realizadas pelo sistema &#250;nico de sa&#250;de (SUS) em 2019,<sup><xref ref-type="bibr" rid="B1">1</xref></sup> estar&#237;amos falando aproximadamente de 35.000 pacientes submetidos a coronariografia desnecessariamente por ano! Avan&#231;amos muito com esses novos &#8220;super&#8221; marcadores, melhoramos nosso diagn&#243;stico e capacidade de prever eventos, mas &#233; a hora de saber a melhor maneira de utiliz&#225;-los na pr&#225;tica cl&#237;nica e reduzir procedimentos desnecess&#225;rios.</p>
  </body>
  <back>
    <fn-group>
      <fn fn-type="other" id="fn1">
        <p>Minieditorial referente ao artigo: Troponina I por Percentil 99 da Defini&#231;&#227;o Universal de Infarto do Mioc&#225;rdio versus Ponto de Corte de Melhor Acur&#225;cia em S&#237;ndromes Coron&#225;rias Agudas</p>
      </fn>
    </fn-group>
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  <sub-article article-type="translation" id="S01" 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>Troponin &#8211; Use it wisely. And as Another Instrument in the Clinic</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <contrib-id contrib-id-type="orcid">0000-0003-0570-4368</contrib-id>
          <name>
            <surname>Wang</surname>
            <given-names>Ricardo</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Figueiredo</surname>
            <given-names>Estev&#257;o Lanna</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>1</sup>
          </xref>
        </contrib>
        <aff id="aff2">
          <label>1</label>
          <addr-line>
            <named-content content-type="city">Belo Horizonte</named-content>
            <named-content content-type="state">MG</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Instituto Orizonti Hospital das Cl&#237;nicas da Universidade Federal e Minhas Gerais, Belo Horizonte, MG &#8211; Brazil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><bold>Mailing Address: Ricardo Wang</bold> &#8226; Rua Jos&#233; Patroc&#237;nio Pontes, 1355. Postal Code <postal-code>30210-090</postal-code>, Belo Horizonte, MG &#8211; Brazil. E-mail: <email>rwang@terra.com.br</email></corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>Myocardial Infarction</kwd>
        <kwd>Biomarkers</kwd>
        <kwd>Troponin</kwd>
        <kwd>Mortality</kwd>
        <kwd>Epidemiology</kwd>
        <kwd>Myocardial Ischemia</kwd>
        <kwd>Myocardial Revascularization</kwd>
        <kwd>Acute Coronary Syndrome</kwd>
        <kwd>Prognosis</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>Acute myocardial infarction (AMI) and stable chronic coronary disease are the main causes of mortality in Brazil.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> In 2019, it was responsible for more than 170,000 deaths in Brazil. Given its severity, the Cardiology made a great effort to constantly improve the tools for the correct diagnosis to avoid the release of patients with Acute Coronary Syndrome (ACS) and its clinical and legal consequences. They are considered pillars for the diagnosis and a good anamnesis with the characterization of the type of pain, electrocardiographic changes, and biomarkers (mainly troponin).</p>
      <p>Biomarkers play an important role in recognizing ACS, and diagnostic algorithms have adapted as they evolve. At first, they were nonspecific markers (e.g., lactic dehydrogenase, oxacetic transaminase, total creatine phosphokinase &#8211; CK). Then they evolved to a slightly more specific marker (creatine phosphokinase MB portion) with its difficult criteria: e.g., total CK/MB). Finally, we have an extremely specific marker of myocardial injuries, such as troponin. The evolution of biomarkers has allowed the simplification of chest pain protocols and the reduction of inappropriate discharge of patients with ACS.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> Due to troponin&#8217;s high sensitivity and specificity, in the fourth consensus on the universal definition of myocardial infarction, it was concluded that to establish the clinical diagnosis, an elevation above the 99th percentile of this biomarker was associated with clinical evidence of myocardial infarction ischemia.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Given the low cutoff for troponin, there are doubts in this consensus regarding the clinical relevance.</p>
      <p>In this issue of the <italic>Arquivos Brasileiros de Cardiologia</italic>, Tapas-Filho et al.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> compare the 99th percentile cutoff level versus the troponin manufacturer&#8217;s label cutoff. They observed that the troponin values above the 99th percentile used by the 4<sup>th</sup> Universal Definition of Infarction were useful in prognosis; they could predict the composite outcome of death and reinfarction within 30 days. An additional observation is that minimally elevated troponin levels made it possible to stratify patients better and identify those most likely to benefit from early invasive strategy and coronary revascularization procedures.</p>
      <p>Despite supporting the recommendations, some issues are to be analyzed regarding the published work. First, it is a single-center registry with a limited sample (494 patients), among which patients with troponin between 0.034 and 0.12ng/dL were only 39. Second, we observed that the mortality of the groups is low (2.4% to 3.9%) in the registry, which can be explained by the low-risk population (GRACE SCORE: 102 (trop &gt; 0.034-0.12ng/dL) x 120 (trop &gt;0.12 ng/dL)). Another possible explanation for the low mortality mentioned by the authors is the high rate of invasive strategy and early coronary revascularization. Higher troponin levels had a higher incidence of reinfarction (16.2% versus 4.8%) and occurred mainly in the first 15 days. In the study, the causes of this increase were not clear. We can speculate: incomplete revascularization? Procedure-related infarction (type IV or V AMI)? These are issues to be carefully considered.</p>
      <p>In addition to the limitation of the study sample size, another point of attention is the follow-up period. Compared with the SWEDEHEART registry (with more than 48,000 patients included) and the analysis of this subgroup (9,800 patients), followed for ten years, an increase in cardiovascular events was observed in this population in the order of 15.4%.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> This fact reinforces the importance of small increases in troponin as a long-term prognostic marker.</p>
      <p>If, on the one hand, lowering the cutoff point of biomarkers is a predictor of events, on the other hand, there is concern about reducing the specificity of the test, with an increase in the number of false positives,<sup><xref ref-type="bibr" rid="B6">6</xref></sup> which could lead to unnecessary procedures, and an increase, for example, coronary angiographies without coronary lesions (so-called &#8220;white catheters&#8221;), which can stigmatize the patient and expose them to complications related to care. In the Tapas-Filho<sup><xref ref-type="bibr" rid="B4">4</xref></sup> registry, we observed that in patients with lower troponin levels, 92% underwent coronary angiography, and the revascularization rate was &gt; 75% (similar to the higher troponin group). We emphasize that, in general, 25% of patients could not have undergone invasive tests.</p>
      <p>From our point of view, the time is now to look for markers that prevent patients from being unnecessarily submitted to the invasive strategy. To have the dimension of the numbers, if we consider approximately 110,000 revascularizations performed by the Unified Health System (SUS) in 2019,<sup><xref ref-type="bibr" rid="B1">1</xref></sup> we would be talking about approximately 35,000 patients undergoing coronary angiography unnecessarily per year! We have advanced a lot with these new &#8220;super&#8221; markers, we have improved our diagnosis and ability to predict events, but it is time to know the best way to use them in clinical practice and reduce unnecessary procedures.</p>
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          <p>Short Editorial related to the article: Universal Definition of Myocardial Infarction 99th Percentile versus Diagnostic Cut-off Value of Troponin I for Acute Coronary Syndromes</p>
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