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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">84p7MNSrypxktHchfh4jQTk</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2025001000301</article-id>
      <article-id pub-id-type="other">00301</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20250109</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo Original</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Acur&#225;cia da Cronologia do Bloqueio de Ramo Esquerdo e dos Crit&#233;rios Eletrocardiogr&#225;ficos para o Diagn&#243;stico de Infarto Agudo do Mioc&#225;rdio: Revis&#227;o Sistem&#225;tica e Metan&#225;lise</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-3835-6067</contrib-id>
          <name>
            <surname>Alencar</surname>
            <given-names>Jos&#233; Nunes de</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Obten&#231;&#227;o de dados</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>An&#225;lise estat&#237;stica e Reda&#231;&#227;o do manuscrito</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lima</surname>
            <given-names>Gleydson Wesley Freire</given-names>
          </name>
          <role>Obten&#231;&#227;o de dados</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Geraldo</surname>
            <given-names>Haissa Assad dos Santos</given-names>
          </name>
          <role>Obten&#231;&#227;o de dados</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Fernandes</surname>
            <given-names>Rinaldo Carvalho</given-names>
          </name>
          <role>Obten&#231;&#227;o de dados</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Scheffer</surname>
            <given-names>Matheus Kiszka</given-names>
          </name>
          <role>Obten&#231;&#227;o de dados</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Felicioni</surname>
            <given-names>Sandro Pinelli</given-names>
          </name>
          <role>Obten&#231;&#227;o de dados</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Marchi</surname>
            <given-names>Mariana Fuziy Nogueira De</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">Instituto Dante Pazzanese de Cardiologia</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 Dante Pazzanese de Cardiologia, S&#227;o Paulo, SP &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c01"><label>Correspond&#234;ncia:</label> Jos&#233; Nunes de Alencar Neto &#8226; Instituto Dante Pazzanese de Cardiologia &#8211; Av. Dr. Dante Pazzanese, 500. CEP 04012-091, Vila Mariana, S&#227;o Paulo, SP &#8211; Brasil E-mail: <email>jose.alencar@dantepazzanese.org.br</email> </corresp>
        <fn fn-type="edited-by">
          <label>Editor respons&#225;vel pela revis&#227;o:</label>
          <p>Marcio Bittencourt</p>
        </fn>
        <fn fn-type="conflict">
          <label>Potencial conflito de interesse:</label>
          <p>N&#227;o h&#225; conflito com o presente artigo.</p>
        </fn>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>03</day>
        <month>11</month>
        <year>2025</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>10</month>
        <year>2025</year>
      </pub-date>
      <volume>122</volume>
      <issue>10</issue>
      <elocation-id>e20250109</elocation-id>
      <history>
        <date date-type="received">
          <day>17</day>
          <month>02</month>
          <year>2025</year>
        </date>
        <date date-type="rev-recd">
          <day>21</day>
          <month>05</month>
          <year>2025</year>
        </date>
        <date date-type="accepted">
          <day>18</day>
          <month>06</month>
          <year>2025</year>
        </date>
      </history>
      <permissions>
        <copyright-statement>Copyright &#169; 2025 SciELO</copyright-statement>
        <copyright-year>2025</copyright-year>
        <copyright-holder>SciELO</copyright-holder>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>Este &#233; um artigo de acesso aberto distribu&#237;do sob os termos da licen&#231;a de atribui&#231;&#227;o pelo Creative Commons</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Resumo</title>
        <sec>
          <title>Fundamento</title>
          <p> A utilidade diagn&#243;stica do bloqueio de ramo esquerdo (BRE) novo ou presumivelmente novo para o infarto agudo do mioc&#225;rdio (IAM), no contexto da s&#237;ndrome coronariana aguda (SCA), permanece controversa.</p>
        </sec>
        <sec>
          <title>Objetivo</title>
          <p> Avaliar se a cronologia do BRE prediz IAM e comparar sua acur&#225;cia diagn&#243;stica com os crit&#233;rios eletrocardiogr&#225;ficos (ECG) isqu&#234;micos, com &#234;nfase nos Crit&#233;rios de Sgarbossa Modificados (CSM).</p>
        </sec>
        <sec>
          <title>M&#233;todos</title>
          <p> Foram realizadas buscas nas bases de dados PubMed e Scopus por estudos envolvendo pacientes com SCA e BRE at&#233; dezembro de 2023. Foram calculadas sensibilidade, especificidade, raz&#227;o de verossimilhan&#231;a positiva (RV+), raz&#227;o de verossimilhan&#231;a negativa (RV&#8211;) e raz&#227;o de chances diagn&#243;stica (<italic>diagnostic odds ratio</italic>, DOR) para avaliar a acur&#225;cia diagn&#243;stica. Tamb&#233;m foram analisados dados de incid&#234;ncia e mortalidade. O risco de vi&#233;s foi avaliado por meio da Newcastle-Ottawa Scale (NOS) e do instrumento revisado Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2).</p>
        </sec>
        <sec>
          <title>Resultados</title>
          <p> Um total de 51 estudos foi inclu&#237;do. O BRE esteve presente em 3,3% dos casos de SCA e foi associado a maior mortalidade intra-hospitalar. A distin&#231;&#227;o entre BRE novo e antigo demonstrou valor diagn&#243;stico nulo: RV+ 1,30 (IC 95%: 0,75 a 1,85), RV&#8211; 0,90 (IC 95%: 0,79 a 1,02) e DOR 1,44 (IC 95%: 0,93 a 2,24); todos os intervalos de confian&#231;a cruzaram o valor nulo (1,0). Em contraste, os CSM demonstraram sensibilidade de 83,6% (IC 95%: 55,4 a 95,5%) e especificidade de 92,6% (IC 95%: 78,9 a 97,7%) para IAM oclusivo confirmado por angiografia, com RV+ de 11,34 (IC 95%: 3,67 a 34,99) e RV&#8211; de 0,18 (IC 95%: 0,054 a 0,575).</p>
        </sec>
        <sec>
          <title>Conclus&#227;o</title>
          <p> A cronologia do BRE, isoladamente, n&#227;o altera de forma significativa a probabilidade de IAM. Crit&#233;rios ECG isqu&#234;micos &#8212; especialmente os CSM &#8212; apresentam acur&#225;cia diagn&#243;stica substancialmente superior e devem nortear a tomada de decis&#227;o cl&#237;nica em pacientes com SCA e BRE.</p>
        </sec>
      </abstract>
      <abstract abstract-type="graphical">
        <p>
          <fig id="f01">
            <label>Figura Central:</label>
            <caption>
              <title>Acur&#225;cia da Cronologia do Bloqueio de Ramo Esquerdo e dos Crit&#233;rios Eletrocardiogr&#225;ficos para o Diagn&#243;stico de Infarto Agudo do Mioc&#225;rdio: Revis&#227;o Sistem&#225;tica e Metan&#225;lise</title>
              <p>BRE: bloqueio do ramo esquerdo; DOR: diagnostic odds ratio; IAM: infarto agudo do mioc&#225;rdio; RV+: raz&#227;o de verossimilhan&#231;a positiva; RV&#8211;: raz&#227;o de verossimilhan&#231;a negativa; SCA: s&#237;ndrome coronariana aguda.</p>
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      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave</title>
        <kwd>Infarto do Mioc&#225;rdio</kwd>
        <kwd>Eletrocardiografia</kwd>
        <kwd>S&#237;ndrome Coronariana Aguda</kwd>
      </kwd-group>
      <counts>
        <fig-count count="12"/>
        <table-count count="4"/>
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        <ref-count count="84"/>
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    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>Pacientes que se apresentam com suspeita de s&#237;ndrome coronariana aguda (SCA) e bloqueio de ramo esquerdo (BRE) representam um desafio cl&#237;nico complexo. A presen&#231;a de BRE novo ou presumivelmente novo nesse contexto tem gerado consider&#225;vel debate, especialmente quanto &#224;s suas implica&#231;&#245;es diagn&#243;sticas e terap&#234;uticas. Ainda n&#227;o est&#225; claro se o BRE novo ou presumivelmente novo deve ser considerado equivalente eletrocardiogr&#225;fico (ECG) ao infarto agudo do mioc&#225;rdio com supradesnivelamento do segmento ST (IAMCSST), o que justifica investiga&#231;&#245;es adicionais sobre sua relev&#226;ncia cl&#237;nica.<sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
      <p>As diretrizes de 2004 do American College of Cardiology (ACC) e da American Heart Association (AHA) inicialmente recomendaram a terapia de reperfus&#227;o precoce &#8212; por fibrin&#243;lise ou interven&#231;&#227;o coronariana percut&#226;nea (ICP) &#8212; para pacientes com BRE novo ou presumivelmente novo, atribuindo a essa conduta uma indica&#231;&#227;o de classe I.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> No entanto, essa estrat&#233;gia passou a ser cada vez mais questionada devido &#224; elevada taxa de cateterismos card&#237;acos realizados em pacientes sem art&#233;ria culpada oclu&#237;da, o que levanta preocupa&#231;&#245;es quanto aos riscos associados ao uso desnecess&#225;rio de fibrinol&#237;ticos e de procedimentos invasivos.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
      <p>Essas mudan&#231;as de perspectiva ressaltam a necessidade de reavaliar o papel do BRE no diagn&#243;stico e no manejo do infarto agudo do mioc&#225;rdio (IAM).<sup><xref ref-type="bibr" rid="B4">4</xref></sup> As diretrizes mais recentes do American College of Cardiology (ACC) e da American Heart Association (AHA) j&#225; n&#227;o consideram o BRE como equivalente autom&#225;tico ao IAMCSST.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Em contraste, as diretrizes europeias de 2023 recomendam tratar pacientes que se apresentam com BRE e sinais cl&#237;nicos sugestivos de SCA como casos de IAMCSST, independentemente de o BRE ser previamente conhecido.<sup><xref ref-type="bibr" rid="B6">6</xref></sup></p>
      <p>Buscando responder a quest&#245;es clinicamente relevantes em um contexto pr&#225;tico, esta metan&#225;lise teve como objetivo quantificar a preval&#234;ncia de BRE entre pacientes que se apresentam com suspeita de SCA. Adicionalmente, por meio da an&#225;lise de dados de mortalidade, investigamos se pacientes com BRE apresentam taxas de mortalidade hospitalar mais elevadas em compara&#231;&#227;o &#224;queles com outras altera&#231;&#245;es de condu&#231;&#227;o ou achados ECG.</p>
      <p>Tamb&#233;m avaliamos se a identifica&#231;&#227;o clara de um BRE novo &#8212; ou a capacidade de estimar sua temporalidade &#8212; constitui um marcador confi&#225;vel para IAM, conforme determinado pela eleva&#231;&#227;o de marcadores de necrose mioc&#225;rdica ou pela presen&#231;a de oclus&#227;o coronariana aguda (OCA) confirmada por angiografia em pacientes com suspeita de SCA. Por fim, investigamos se crit&#233;rios ECG espec&#237;ficos para isquemia no contexto de BRE apresentam acur&#225;cia diagn&#243;stica suficiente para aplica&#231;&#227;o rotineira na pr&#225;tica cl&#237;nica.</p>
      <p>Esta an&#225;lise abrangente, conduzida de acordo com as diretrizes Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA)<sup><xref ref-type="bibr" rid="B7">7</xref>,<xref ref-type="bibr" rid="B8">8</xref></sup> e Meta-analyses Of Observational Studies in Epidemiology (MOOSE)<sup><xref ref-type="bibr" rid="B9">9</xref></sup> busca oferecer uma compreens&#227;o aprofundada do papel do BRE na SCA e fornecer subs&#237;dios relevantes para a tomada de decis&#227;o cl&#237;nica.</p>
    </sec>
    <sec sec-type="methods">
      <title>M&#233;todos</title>
      <p>Nesta revis&#227;o sistem&#225;tica, inclu&#237;mos estudos envolvendo pacientes com SCA ou suspeita de SCA na presen&#231;a de BRE novo ou presumivelmente novo, BRE isqu&#234;mico ou BRE decorrente de estimula&#231;&#227;o artificial. Nosso objetivo principal foi avaliar a acur&#225;cia diagn&#243;stica do BRE novo ou do BRE associado a crit&#233;rios isqu&#234;micos no ECG, comparando sensibilidade e especificidade em rela&#231;&#227;o a padr&#245;es de refer&#234;ncia como biomarcadores card&#237;acos (CK-MB ou troponina) e angiografia coronariana.</p>
      <p>Tamb&#233;m buscamos avaliar a preval&#234;ncia e a mortalidade intra-hospitalar associadas ao BRE no contexto da SCA. Os estudos foram inclu&#237;dos independentemente do idioma e do status de publica&#231;&#227;o, abrangendo todos os registros dispon&#237;veis desde a cria&#231;&#227;o das bases de dados at&#233; dezembro de 2023. A estrat&#233;gia de busca completa encontra-se no Material Suplementar 1.</p>
      <p>Nossa busca foi realizada at&#233; dezembro de 2023 nas bases PubMed e Scopus. A estrat&#233;gia de pesquisa foi elaborada especificamente para identificar estudos pertinentes ao BRE no contexto de SCA, conforme detalhado nos materiais suplementares. Foram aplicados filtros para adequar os resultados aos crit&#233;rios de elegibilidade, com &#234;nfase no status de publica&#231;&#227;o e no tipo de estudo, garantindo relev&#226;ncia e precis&#227;o.</p>
      <p>Dois revisores (H.G. e G.L.) examinaram, de forma independente, t&#237;tulos e resumos. Diverg&#234;ncias foram solucionadas por um terceiro revisor (R.F.). A avalia&#231;&#227;o dos textos completos foi posteriormente conduzida por outros dois revisores (J.A. e M.M.). Todo o processo de triagem foi gerenciado com o aux&#237;lio da ferramenta online HubMeta.<sup><xref ref-type="bibr" rid="B10">10</xref></sup></p>
      <p>Aplicamos crit&#233;rios de exclus&#227;o rigorosos, desconsiderando estudos que abordavam outras anormalidades de condu&#231;&#227;o, BRE n&#227;o relacionado &#224; isquemia aguda, diretrizes cl&#237;nicas, artigos de revis&#227;o, relatos de caso, metan&#225;lises ou revis&#245;es sistem&#225;ticas pr&#233;vias, estudos sobre doen&#231;a coronariana cr&#244;nica ou aqueles que tratavam da SCA sem envolver explicitamente BRE novo ou presumivelmente novo. Tamb&#233;m foram exclu&#237;dos estudos que enfocavam m&#233;todos diagn&#243;sticos distintos do ECG em repouso, bem como aqueles voltados para a s&#237;ndrome do BRE doloroso.</p>
      <sec>
        <title>Defini&#231;&#245;es do teste &#237;ndice e dos desfechos</title>
        <p>O BRE foi definido como uma dura&#231;&#227;o do QRS &#8805; 120 ms e morfologia caracter&#237;stica do QRS, incluindo entalhe ou escavamento no ter&#231;o m&#233;dio do complexo QRS em pelo menos duas das seguintes deriva&#231;&#245;es: V1, V2, V5, V6, I e aVL. Os crit&#233;rios diagn&#243;sticos tamb&#233;m inclu&#237;ram atraso no pico da onda R em V5&#8211;V6 superior a 60 ms. No plano horizontal, os achados inclu&#237;ram padr&#227;o QS ou rS em V1 com supradesnivelamento do segmento ST (SST) e onda T positiva e assim&#233;trica, bem como uma onda R proeminente em V6 acompanhada por onda T negativa e assim&#233;trica. Quando a dura&#231;&#227;o do QRS &#233; inferior a 140 ms, a onda T em V6 pode se apresentar positiva.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> Contudo, devido &#224; longa abrang&#234;ncia temporal desta revis&#227;o, a defini&#231;&#227;o de BRE evoluiu ao longo dos anos. Assim, foi aceita a defini&#231;&#227;o utilizada pelos investigadores originais de cada estudo &#224; &#233;poca da respectiva condu&#231;&#227;o.</p>
        <p>De modo semelhante, a defini&#231;&#227;o de IAM tamb&#233;m se modificou com o tempo, incorporando diferentes crit&#233;rios. Um diagn&#243;stico baseado em biomarcadores foi geralmente aceito na presen&#231;a de eleva&#231;&#227;o de marcadores como AST, ALT, CPK, CK-MB ou troponina. Estudos mais recentes adotaram a defini&#231;&#227;o universal de IAM, que inclui altera&#231;&#245;es isqu&#234;micas no ECG, como SST ou BRE novo ou presumivelmente novo.<sup><xref ref-type="bibr" rid="B12">12</xref>,<xref ref-type="bibr" rid="B13">13</xref></sup></p>
        <p>Outro desfecho avaliado foi a OCA confirmada por angiografia, definida como a presen&#231;a &#8212; ou suspeita de presen&#231;a &#8212; de uma OCA no exame angiogr&#225;fico. Esse desfecho &#233; considerado um desfecho composto substitutivo, geralmente envolvendo apresenta&#231;&#227;o cl&#237;nica compat&#237;vel, presen&#231;a de les&#227;o coronariana e n&#237;veis de troponina marcadamente elevados.<sup><xref ref-type="bibr" rid="B14">14</xref></sup> Essa defini&#231;&#227;o, mais contempor&#226;nea e precisa, foi destacada no texto sempre que dispon&#237;vel.</p>
      </sec>
      <sec>
        <title>An&#225;lise estat&#237;stica</title>
        <p>Para desfechos dicot&#244;micos, como preval&#234;ncia e mortalidade, foram realizadas metan&#225;lises de efeitos aleat&#243;rios utilizando o software Onlinemeta (vers&#227;o 1.0: 2022.3.15).<sup><xref ref-type="bibr" rid="B15">15</xref></sup> A heterogeneidade foi avaliada e ilustrada por meio da estat&#237;stica bayesiana I<sup><xref ref-type="bibr" rid="B2">2</xref></sup>,<sup><xref ref-type="bibr" rid="B16">16</xref></sup> com an&#225;lises de subgrupos planejadas com base em diferen&#231;as populacionais e metodol&#243;gicas. Heterogeneidade elevada foi definida como I<sup>2</sup> &gt; 75%.<sup><xref ref-type="bibr" rid="B17">17</xref></sup></p>
        <p>Para avaliar o vi&#233;s de publica&#231;&#227;o potencial, foram utilizados gr&#225;ficos em funil, al&#233;m dos testes de Egger<sup><xref ref-type="bibr" rid="B18">18</xref></sup> e Begg.<sup><xref ref-type="bibr" rid="B19">19</xref></sup> Valores p &lt; 0,05 foram considerados indicativos de vi&#233;s de publica&#231;&#227;o significativo. Todos os gr&#225;ficos e testes relacionados est&#227;o dispon&#237;veis no Material Suplementar 1.</p>
        <p>Para os desfechos de acur&#225;cia diagn&#243;stica, foi conduzida uma metan&#225;lise com o pacote <italic>mada</italic> no R, aplicando o modelo bivariado de Reitsma.<sup><xref ref-type="bibr" rid="B20">20</xref>,<xref ref-type="bibr" rid="B21">21</xref></sup> Foram calculadas as estimativas agrupadas de sensibilidade, especificidade, raz&#245;es de verossimilhan&#231;a positiva (RV+) e negativa (RV&#8722;), bem como a raz&#227;o de chances diagn&#243;stica (<italic>diagnostic odds ratio</italic>, DOR), todas com intervalos de confian&#231;a de 95% estimados pelo m&#233;todo delta.</p>
        <p>O risco de vi&#233;s foi avaliado por meio da Newcastle-Ottawa Scale (NOS)<sup><xref ref-type="bibr" rid="B22">22</xref></sup> para estudos caso-controle e pela vers&#227;o revisada da Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2)<sup><xref ref-type="bibr" rid="B23">23</xref></sup> para estudos de acur&#225;cia diagn&#243;stica. As visualiza&#231;&#245;es foram geradas com a ferramenta online <italic>robvis</italic>.<sup><xref ref-type="bibr" rid="B24">24</xref></sup></p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Resultados</title>
      <p>A busca nas bases de dados eletr&#244;nicas resultou em 2.700 artigos. Ap&#243;s a remo&#231;&#227;o de duplicatas, restaram 1.967 registros &#250;nicos para a triagem inicial. A sele&#231;&#227;o por t&#237;tulo e resumo reduziu esse n&#250;mero para 146 artigos. Ap&#243;s a avalia&#231;&#227;o completa dos textos, 51 estudos atenderam aos crit&#233;rios de inclus&#227;o e foram incorporados &#224; metan&#225;lise.</p>
      <p>Os detalhes do processo de sele&#231;&#227;o dos estudos est&#227;o apresentados na <xref ref-type="fig" rid="f02">Figura 1</xref>, na se&#231;&#227;o de Resultados. As estrat&#233;gias de busca completas e as caracter&#237;sticas basais dos estudos inclu&#237;dos encontram-se no Material Suplementar 1.</p>
      <p>
        <fig id="f02">
          <label>Figura 1</label>
          <caption>
            <title>&#8211; Fluxograma do processo de sele&#231;&#227;o dos estudos, desde a busca inicial nas bases de dados at&#233; a inclus&#227;o final de 51 estudos na metan&#225;lise.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-122-10-e20250109-50109-gf01.tif"/></fig>
      </p>
      <sec>
        <title>Preval&#234;ncia de BRE em SCA</title>
        <p>Um subconjunto de 29 estudos investigou a preval&#234;ncia de BRE novo, presumivelmente novo ou estabelecido entre 221.261 casos consecutivos com suspeita de SCA.<sup><xref ref-type="bibr" rid="B25">25</xref>-<xref ref-type="bibr" rid="B53">53</xref></sup> Observou-se heterogeneidade substancial no diagn&#243;stico de SCA, com um &#237;ndice I<sup>2</sup> de 99%. No geral, 3,3% (IC 95%: 2,7% a 4,1%) dos casos de SCA apresentaram BRE, independentemente de sua cronologia. Um resumo gr&#225;fico desses achados &#233; apresentado na <xref ref-type="fig" rid="f03">Figura 2</xref>.</p>
        <p>
          <fig id="f03">
            <label>Figura 2</label>
            <caption>
              <title>&#8211; Forest plot da preval&#234;ncia de BRE entre pacientes com SCA em 29 estudos. As estimativas individuais de cada estudo s&#227;o apresentadas com seus respectivos IC 95%, juntamente com a preval&#234;ncia agrupada e as estat&#237;sticas de heterogeneidade. BRE: bloqueio de ramo esquerdo; SCA: s&#237;ndrome coronariana aguda.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-122-10-e20250109-50109-gf02.tif"/></fig>
        </p>
        <p>N&#227;o foi detectado vi&#233;s de publica&#231;&#227;o significativo, conforme demonstrado pelo gr&#225;fico de funil dispon&#237;vel no Material Suplementar 1.</p>
      </sec>
      <sec>
        <title>Mortalidade intra-hospitalar do BRE em SCA</title>
        <p>Para avaliar a mortalidade intra-hospitalar entre pacientes com SCA, conduzimos uma metan&#225;lise com efeito aleat&#243;rio de 14 estudos envolvendo 418.417 indiv&#237;duos que se apresentaram com dor tor&#225;cica.<sup><xref ref-type="bibr" rid="B27">27</xref>-<xref ref-type="bibr" rid="B29">29</xref>,<xref ref-type="bibr" rid="B32">32</xref>,<xref ref-type="bibr" rid="B34">34</xref>,<xref ref-type="bibr" rid="B39">39</xref>,<xref ref-type="bibr" rid="B42">42</xref>,<xref ref-type="bibr" rid="B44">44</xref>,<xref ref-type="bibr" rid="B45">45</xref>,<xref ref-type="bibr" rid="B49">49</xref>,<xref ref-type="bibr" rid="B54">54</xref>-<xref ref-type="bibr" rid="B57">57</xref></sup> A presen&#231;a de BRE n&#227;o resultou em uma taxa de mortalidade significativamente maior em compara&#231;&#227;o ao bloqueio do ramo direito (BRD). No entanto, compara&#231;&#245;es entre pacientes com BRE e aqueles com IAMCSST ou com complexos QRS normais sem SST revelaram ORs n&#227;o ajustadas significativamente aumentadas.</p>
        <p>Dois estudos compararam especificamente a mortalidade entre BRE novo e antigo. Dentre eles, apenas um utilizou a presen&#231;a de OCA confirmada por angiografia para definir IAM.<sup><xref ref-type="bibr" rid="B39">39</xref></sup> Resultados detalhados e distribui&#231;&#245;es dos dados est&#227;o apresentados na <xref ref-type="fig" rid="f04">Figura 3</xref>.</p>
        <p>
          <fig id="f04">
            <label>Figure 3</label>
            <caption>
              <title>&#8211; Forest plots das ORs n&#227;o ajustadas para mortalidade hospitalar em pacientes com SCA de acordo com diferentes apresenta&#231;&#245;es no ECG. Primeiro box: Compara&#231;&#227;o entre BRE e BRD mostra aus&#234;ncia de heterogeneidade significativa (I2 = 19%). Segundo box: Compara&#231;&#227;o entre BRE e IAMCSST tamb&#233;m mostra aus&#234;ncia de heterogeneidade significativa. Terceiro box: Compara&#231;&#227;o entre BRE e pacientes sem BR demonstra alta heterogeneidade (I2 = 87%). Quarto box: Compara&#231;&#227;o entre nBRE e oBRE, sem avalia&#231;&#227;o da heterogeneidade. Cada gr&#225;fico mostra as estimativas individuais dos estudos com IC 95% e as ORs agrupadas, destacando a variabilidade nos desfechos de mortalidade conforme os achados eletrocardiogr&#225;ficos na apresenta&#231;&#227;o. BR: bloqueio de ramo; BRE: bloqueio de ramo esquerdo; BRD: bloqueio de ramo direito; IAMCSST: infarto agudo do mioc&#225;rdio com supradesnivelamento do segmento ST; nBRE: BRE novo; oBRE: BRE antigo; SCA: s&#237;ndrome coronariana aguda.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-122-10-e20250109-50109-gf03.tif"/></fig>
        </p>
      </sec>
      <sec>
        <title>OR do BRE para IAM</title>
        <p>Analisamos a associa&#231;&#227;o entre a presen&#231;a de BRE e a ocorr&#234;ncia de OCA confirmada por angiografia ou de IAM baseado em marcadores de necrose mioc&#225;rdica. Os estudos que compararam esses desfechos em pacientes com e sem BRE foram agrupados para an&#225;lise.<sup><xref ref-type="bibr" rid="B30">30</xref>,<xref ref-type="bibr" rid="B34">34</xref>,<xref ref-type="bibr" rid="B36">36</xref>,<xref ref-type="bibr" rid="B37">37</xref>,<xref ref-type="bibr" rid="B39">39</xref>,<xref ref-type="bibr" rid="B44">44</xref>,<xref ref-type="bibr" rid="B51">51</xref>,<xref ref-type="bibr" rid="B58">58</xref>-<xref ref-type="bibr" rid="B60">60</xref></sup> As ORs foram calculadas por meio de um modelo de efeitos aleat&#243;rios para estimar a for&#231;a da associa&#231;&#227;o entre os estudos.</p>
        <p>Nos estudos que utilizaram angiografia para confirmar a OCA, a OR combinada foi de 0,226 (IC 95%: 0,092 a 0,557). Para aqueles que utilizaram defini&#231;&#245;es baseadas em biomarcadores, a OR combinada foi de 0,496 (IC 95%: 0,358 a 0,689). A OR geral combinada entre todos os estudos foi de 0,336 (IC 95%: 0,210 a 0,538), com Tau<xref ref-type="bibr" rid="B2"><sup>2</sup></xref> = 0,443 e I<sup>2</sup> = 89%, indicando heterogeneidade substancial.</p>
        <p>Esses achados est&#227;o resumidos na <xref ref-type="fig" rid="f05">Figura 4</xref>. Os gr&#225;ficos de funil e as avalia&#231;&#245;es de vi&#233;s de publica&#231;&#227;o est&#227;o apresentados no Material Suplementar 1.</p>
        <p>
          <fig id="f05">
            <label>Figura 4</label>
            <caption>
              <title>&#8211; Forest plot das ORs para o BRE na predi&#231;&#227;o de OCA confirmada por angiografia e IAM definido por biomarcadores. BRE: bloqueio de ramo esquerdo; IAM: infarto agudo do mioc&#225;rdio; OCA: oclus&#227;o coronariana aguda.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-122-10-e20250109-50109-gf04.tif"/></fig>
        </p>
      </sec>
      <sec>
        <title>Acur&#225;cia diagn&#243;stica do BRE novo/presumivelmente novo</title>
        <p>Nos estudos que avaliaram a acur&#225;cia diagn&#243;stica do BRE claramente novo em compara&#231;&#227;o com blocos antigos ou de cronologia indeterminada,<sup><xref ref-type="bibr" rid="B36">36</xref>,<xref ref-type="bibr" rid="B40">40</xref>,<xref ref-type="bibr" rid="B61">61</xref>-<xref ref-type="bibr" rid="B65">65</xref></sup> foram analisados 1.229 pacientes. A sensibilidade agrupada foi de 0,321 (IC 95%: 0,240 a 0,402), a especificidade foi de 0,753 (IC 95%: 0,612 a 0,894), a RV+ foi de 1,30 (IC 95%: 0,751 a 1,850) e a RV&#8211; foi de 0,902 (IC 95%: 0,786 a 1,017). A DOR foi de 1,442 (IC 95%: 0,927 a 2,243), com todos os intervalos de confian&#231;a cruzando o valor nulo de 1,0, indicando aus&#234;ncia de poder discriminativo relevante.</p>
        <p>Quando os blocos de cronologia indeterminada foram agrupados com os BRE novos e comparados aos BRE antigos, em um total de 848 pacientes,<sup><xref ref-type="bibr" rid="B40">40</xref>,<xref ref-type="bibr" rid="B61">61</xref>,<xref ref-type="bibr" rid="B62">62</xref>,<xref ref-type="bibr" rid="B64">64</xref></sup> a sensibilidade foi de 0,633 (IC 95%: 0,376 a 0,891), a especificidade de 0,386 (IC 95%: 0,326 a 0,446), a RV+ de 1,032 (IC 95%: 0,653 a 1,411) e a RV&#8211; de 0,949 (IC 95%: 0,343 a 1,556). A DOR resultante foi de 1,087 (IC 95%: 0,520 a 2,271), novamente sem valor diagn&#243;stico significativo.</p>
        <p>Apenas um estudo<sup><xref ref-type="bibr" rid="B63">63</xref></sup> utilizou a OCA confirmada por angiografia como padr&#227;o-ouro para definir IAM, relatando sensibilidade de 37,5% e especificidade de 67,39%. Informa&#231;&#245;es adicionais est&#227;o dispon&#237;veis na <xref ref-type="table" rid="t1">Tabela 1</xref> e na <xref ref-type="fig" rid="f06">Figura 5</xref>.</p>
        <p>
          <table-wrap id="t1">
            <label>Tabela 1</label>
            <caption>
              <title>&#8211; Acur&#225;cia diagn&#243;stica da cronologia do BRE na identifica&#231;&#227;o de IAM. Compara&#231;&#227;o entre BRE novo vs BRE indeterminado ou antigo, e entre BRE novo ou indeterminado vs BRE antigo, incluindo sensibilidade, especificidade e raz&#245;es de verossimilhan&#231;a com base em dados individuais de pacientes</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Estrat&#233;gia</th>
                  <th>n</th>
                  <th style="font-weight:normal">Sensibilidade (IC 95%)</th>
                  <th style="font-weight:normal">Especificidade (IC 95%)</th>
                  <th>RV+ (IC 95%)</th>
                  <th>RV&#8211; (IC 95%)</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>BRE novo vs BRE indeterminado e antigo</td>
                  <td align="center">1.229</td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,321</p>
                      </list-item>
                      <list-item>
                        <p>(0,240 a 0,402)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,753</p>
                      </list-item>
                      <list-item>
                        <p>(0,612 a 0,894)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>1,30</p>
                      </list-item>
                      <list-item>
                        <p>(0,751 a 1,850)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,902</p>
                      </list-item>
                      <list-item>
                        <p>(0,786 a 1,017)</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr>
                  <td>BRE novo ou indeterminado vs BRE antigo</td>
                  <td align="center">848</td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,633</p>
                      </list-item>
                      <list-item>
                        <p>(0,376 a 0,891)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,386</p>
                      </list-item>
                      <list-item>
                        <p>(0,326 a 0,446)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>1,032</p>
                      </list-item>
                      <list-item>
                        <p>(0,653 a 1,411)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,949</p>
                      </list-item>
                      <list-item>
                        <p>(0,343 a 1,556)</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN1">
                <p>BRE: bloqueio de ramo esquerdo.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </p>
        <p>
          <fig id="f06">
            <label>Figura 5</label>
            <caption>
              <title>&#8211; Forest plots mostrando a sensibilidade e especificidade agrupadas com intervalos de confian&#231;a de 95% para duas compara&#231;&#245;es diagn&#243;sticas envolvendo a cronologia do BRE. Pain&#233;is superiores: compara&#231;&#227;o entre BRE novo ou presumivelmente novo e BRE indeterminado ou antigo. Pain&#233;is inferiores: compara&#231;&#227;o entre BRE novo ou indeterminado e BRE antigo. Ambas as an&#225;lises foram conduzidas em pacientes com dor tor&#225;cica e avaliadas quanto &#224; OCA confirmada por angiografia ou IAM baseado em biomarcadores. BRE: bloqueio de ramo esquerdo; IAM: infarto agudo do mioc&#225;rdio; OCA: oclus&#227;o coronariana aguda.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-122-10-e20250109-50109-gf05.tif"/></fig>
        </p>
      </sec>
      <sec>
        <title>Acur&#225;cia diagn&#243;stica dos crit&#233;rios ECG</title>
        <p>Esta revis&#227;o tamb&#233;m avaliou o desempenho diagn&#243;stico de crit&#233;rios ECG consagrados para o diagn&#243;stico de IAM. Esses crit&#233;rios, amplamente citados na literatura, foram analisados quanto &#224; sensibilidade e especificidade na detec&#231;&#227;o de infarto do mioc&#225;rdio oclusivo (IMO), definido por marcadores de necrose mioc&#225;rdica ou confirmado por angiografia. Um resumo dos achados &#233; apresentado na <xref ref-type="table" rid="t2">Tabela 2</xref>. Os gr&#225;ficos de floresta e a avalia&#231;&#227;o do risco de vi&#233;s com base no instrumento QUADAS est&#227;o dispon&#237;veis no Material Suplementar 1.</p>
        <p>
          <table-wrap id="t2">
            <label>Tabela 2</label>
            <caption>
              <title>&#8211; Acur&#225;cia diagn&#243;stica comparativa dos crit&#233;rios ECG para IAM em pacientes com BRE. S&#227;o apresentados os valores de sensibilidade, especificidade e raz&#245;es de verossimilhan&#231;a positiva (RV+) e negativa (RV&#8211;) para os crit&#233;rios de Sgarbossa, MSC, Crit&#233;rios de Barcelona e sinal de Chapman</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Crit&#233;rio/Sinal</th>
                  <th>n</th>
                  <th style="font-weight:normal">Sensibilidade (IC 95%)</th>
                  <th style="font-weight:normal">Especificidade (IC 95%)</th>
                  <th>RV+ (IC 95%)</th>
                  <th>RV&#8211; (IC 95%)</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>Crit&#233;rios de Sgarbossa</td>
                  <td align="center">2.427</td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,404</p>
                      </list-item>
                      <list-item>
                        <p>(0,227 a 0,610)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,967</p>
                      </list-item>
                      <list-item>
                        <p>(0,922 a 0,987)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>12,384</p>
                      </list-item>
                      <list-item>
                        <p>(5,426 a 28,265)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,616</p>
                      </list-item>
                      <list-item>
                        <p>(0,445 a 0,854)</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr>
                  <td>Sgarbossa &#8211; OCA</td>
                  <td align="center">1.369</td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,426</p>
                      </list-item>
                      <list-item>
                        <p>(0,305 a 0,557)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,962</p>
                      </list-item>
                      <list-item>
                        <p>(0,859 a 0,991)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>11,315</p>
                      </list-item>
                      <list-item>
                        <p>(2,677 a 47,825)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,596</p>
                      </list-item>
                      <list-item>
                        <p>(0,471 a 0,754)</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr>
                  <td>MSC</td>
                  <td align="center">1.702</td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,688</p>
                      </list-item>
                      <list-item>
                        <p>(0,362 a 0,895)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,920</p>
                      </list-item>
                      <list-item>
                        <p>(0,841 a 0,961)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>8,576</p>
                      </list-item>
                      <list-item>
                        <p>(3,952 a 18,608)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,340</p>
                      </list-item>
                      <list-item>
                        <p>(0,135 a 0,857)</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr>
                  <td>Sgarbossa Modificado &#8211; OCA</td>
                  <td align="center">1.161</td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,836</p>
                      </list-item>
                      <list-item>
                        <p>(0,554 a 0,955)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,926</p>
                      </list-item>
                      <list-item>
                        <p>(0,789 a 0,977)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>11,337</p>
                      </list-item>
                      <list-item>
                        <p>(3,672 a 34,999)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,177</p>
                      </list-item>
                      <list-item>
                        <p>(0,054 a 0,575)</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr>
                  <td>Crit&#233;rios de Barcelona</td>
                  <td align="center">887</td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,818</p>
                      </list-item>
                      <list-item>
                        <p>(0,403 a 0,968)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,868</p>
                      </list-item>
                      <list-item>
                        <p>(0,790 a 0,919)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>6,182</p>
                      </list-item>
                      <list-item>
                        <p>(2,815 a 13,577)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,210</p>
                      </list-item>
                      <list-item>
                        <p>(0,042 a 1,049)</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr>
                  <td>Sinal de Chapman</td>
                  <td align="center">104</td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,190</p>
                      </list-item>
                      <list-item>
                        <p>(0,108 a 0,311)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,870</p>
                      </list-item>
                      <list-item>
                        <p>(0,739 a 0,940)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>1,454</p>
                      </list-item>
                      <list-item>
                        <p>(0,582 a 3,635)</p>
                      </list-item>
                    </list>
                  </td>
                  <td align="center">
                    <list list-type="simple">
                      <list-item>
                        <p>0,932</p>
                      </list-item>
                      <list-item>
                        <p>(0,788 a 1,102)</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN2">
                <p>AMI: infarto agudo do mioc&#225;rdio; BRE: bloqueio de ramo esquerdo; ECG: eletrocardiografia; MSC: Modified Sgarbossa Criteria; OCA: oclus&#227;o coronariana aguda.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </p>
        <p>Os <italic>Modified Sgarbossa Criteria</italic> (MSC), desenvolvidos para diagnosticar IAM em pacientes com BRE, incluem: supradesnivelamento de ST concordante &gt;1 mm em deriva&#231;&#245;es com QRS positivo (pontua&#231;&#227;o 5); infradesnivelamento de ST concordante &gt;1 mm em V1&#8211;V3 (pontua&#231;&#227;o 3); e SST excessivamente discordante &gt;5 mm em deriva&#231;&#245;es com QRS negativo (pontua&#231;&#227;o 2). Uma pontua&#231;&#227;o total &#8805;3 &#233; considerada diagn&#243;stica.<sup><xref ref-type="bibr" rid="B66">66</xref></sup></p>
        <p>Aplicados a 2.427 pacientes com BRE, em compara&#231;&#227;o com aqueles sem diagn&#243;stico de IAM ou sem evid&#234;ncia angiogr&#225;fica de OCA, os MSC apresentaram sensibilidade de 0,404 (IC 95%: 0,227 a 0,610) e especificidade de 0,967 (IC 95%: 0,922 a 0,987).<sup><xref ref-type="bibr" rid="B14">14</xref>,<xref ref-type="bibr" rid="B25">25</xref>,<xref ref-type="bibr" rid="B26">26</xref>,<xref ref-type="bibr" rid="B31">31</xref>,<xref ref-type="bibr" rid="B66">66</xref>-<xref ref-type="bibr" rid="B71">71</xref></sup></p>
        <p>Em uma an&#225;lise de sensibilidade restrita aos estudos que utilizaram confirma&#231;&#227;o angiogr&#225;fica do IAM e que exclu&#237;ram pacientes com marca-passo, cinco estudos envolvendo 1.369 pacientes apresentaram uma RV+ de 11,315 e uma RV&#8722; de 0,596.<sup><xref ref-type="bibr" rid="B14">14</xref>,<xref ref-type="bibr" rid="B25">25</xref>,<xref ref-type="bibr" rid="B26">26</xref>,<xref ref-type="bibr" rid="B67">67</xref>,<xref ref-type="bibr" rid="B71">71</xref></sup></p>
        <p>Os MSC diagnosticam IAM em pacientes com BRE com base na presen&#231;a de ao menos um dos seguintes achados: supradesnivelamento de ST concordante &#8805;1 mm em uma ou mais deriva&#231;&#245;es; infradesnivelamento de ST concordante &#8805;1 mm nas deriva&#231;&#245;es V1&#8211;V3; ou SST discordante &#8805;1 mm em qualquer deriva&#231;&#227;o, de forma proporcionalmente excessiva, definido como &#8805;25% da profundidade da onda S precedente.<sup><xref ref-type="bibr" rid="B14">14</xref></sup> Em um total de 1.702 pacientes, os MSC apresentaram sensibilidade de 0,688 (IC 95%: 0,362 a 0,895) e especificidade de 0,920 (IC 95%: 0,841 a 0,961), com RV+ de 8,576 (IC 95%: 3,952 a 18,608) e RV&#8722; de 0,340 (IC 95%: 0,135 a 0,857).<sup><xref ref-type="bibr" rid="B14">14</xref>,<xref ref-type="bibr" rid="B31">31</xref>,<xref ref-type="bibr" rid="B53">53</xref>,<xref ref-type="bibr" rid="B67">67</xref>-<xref ref-type="bibr" rid="B69">69</xref>,<xref ref-type="bibr" rid="B71">71</xref></sup> Ao restringir a an&#225;lise apenas aos estudos que utilizaram o IAM confirmado por angiografia como padr&#227;o de refer&#234;ncia e exclu&#237;ram pacientes com marca-passo, quatro estudos com 1.161 pacientes revelaram uma sensibilidade de 0,836 (IC 95%: 0,554 a 0,955), especificidade de 0,926 (IC 95%: 0,789 a 0,977), RV+ de 11,337 (IC 95%: 3,672 a 34,999) e RV&#8722; de 0,177 (IC 95%: 0,054 a 0,575).<sup><xref ref-type="bibr" rid="B14">14</xref>,<xref ref-type="bibr" rid="B53">53</xref>,<xref ref-type="bibr" rid="B67">67</xref>,<xref ref-type="bibr" rid="B71">71</xref></sup></p>
        <p>Os Crit&#233;rios de Barcelona definem IAM na presen&#231;a de BRE com base em qualquer um dos seguintes achados: supradesnivelamento de ST concordante &#8805;1 mm em qualquer deriva&#231;&#227;o; infradesnivelamento de ST concordante em qualquer deriva&#231;&#227;o; ou desvio de SST discordante &#8805;1 mm em qualquer deriva&#231;&#227;o onde a onda R ou S seja &#8804;6 mm.<sup><xref ref-type="bibr" rid="B72">72</xref></sup> Esses crit&#233;rios foram avaliados em dois estudos, totalizando 887 pacientes, sendo comparados com indiv&#237;duos com BRE que n&#227;o atendiam aos Crit&#233;rios de Barcelona para o diagn&#243;stico de OCA confirmada por angiografia.<sup><xref ref-type="bibr" rid="B67">67</xref>,<xref ref-type="bibr" rid="B72">72</xref></sup> A sensibilidade combinada foi de 0,818 (IC 95%: 0,403 a 0,968) e a especificidade foi de 0,868 (IC 95%: 0,790 a 0,919).</p>
        <p>O sinal de Chapman &#8212; definido pela presen&#231;a de entalhe na fase ascendente da onda R nas deriva&#231;&#245;es I, aVL e V6<sup><xref ref-type="bibr" rid="B73">73</xref></sup> &#8212; foi avaliado quanto &#224; sua utilidade diagn&#243;stica para IAM com base na confirma&#231;&#227;o por biomarcadores em dois estudos da d&#233;cada de 1980, envolvendo um total de 104 pacientes.<sup><xref ref-type="bibr" rid="B74">74</xref>,<xref ref-type="bibr" rid="B75">75</xref></sup> A sensibilidade combinada foi de 0,190 (IC 95%: 0,108 a 0,311) e a especificidade foi de 0,870 (IC 95%: 0,739 a 0,940).</p>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discuss&#227;o</title>
      <p>Nossa an&#225;lise detalhada identificou a presen&#231;a de BRE em 3,3% (IC 95%: 2,7% a 4,1%) das apresenta&#231;&#245;es de SCA. Embora essa preval&#234;ncia possa parecer modesta, ela exige aten&#231;&#227;o cl&#237;nica criteriosa devido ao potencial vi&#233;s de incorpora&#231;&#227;o &#8212; fen&#244;meno em que os crit&#233;rios diagn&#243;sticos se sobrep&#245;em entre o teste &#237;ndice e o padr&#227;o de refer&#234;ncia.<sup><xref ref-type="bibr" rid="B76">76</xref>,<xref ref-type="bibr" rid="B77">77</xref></sup> Em muitos estudos, a presen&#231;a de BRE novo ou presumivelmente novo foi considerada como crit&#233;rio diagn&#243;stico de SCA, o que pode ter superestimado sua preval&#234;ncia.</p>
      <p>Nossa an&#225;lise da mortalidade intra-hospitalar em coortes de SCA sugere que o BRE e o bloqueio de ramo direito (BRD) s&#227;o estatisticamente compar&#225;veis quanto ao risco de mortalidade associado. A OR n&#227;o ajustada para mortalidade intra-hospitalar entre pacientes com BRE foi de 1,135 (IC 95%: 0,975 a 1,322), indicando aus&#234;ncia de diferen&#231;a significativa em compara&#231;&#227;o ao BRD.</p>
      <p>Nossos achados desafiam a no&#231;&#227;o predominante de que a presen&#231;a de BRE &#8212; independentemente de sua cronologia &#8212; deva ser tratada como um IAM <italic>per se</italic>, exigindo terapia de reperfus&#227;o imediata. A OR agrupada de 0,226 (IC 95%: 0,092 a 0,557) sugere que o BRE isoladamente n&#227;o aumenta, por si s&#243;, a probabilidade de IAM. Mesmo utilizando defini&#231;&#245;es baseadas em biomarcadores &#8212; que s&#227;o indicadores menos precisos de IAM &#8212; a OR sobe apenas para 0,496 (IC 95%: 0,358 a 0,689), ainda insuficiente para justificar uma suspeita diagn&#243;stica elevada de IAM Curiosamente, diversos estudos prim&#225;rios inclu&#237;dos nesta an&#225;lise inferiram um alto risco de IAM com base apenas no n&#250;mero absoluto de casos observados em pacientes com BRE, sem compara&#231;&#227;o adequada com popula&#231;&#245;es sem BRE. Essa compara&#231;&#227;o foi essencial para alcan&#231;ar uma interpreta&#231;&#227;o mais precisa e refinada. Essas ORs agrupadas devem ser analisadas &#224; luz de duas fontes principais de vi&#233;s. Primeiro, muitos dos estudos inclu&#237;dos foram conduzidos em um per&#237;odo no qual o &#8220;BRE novo ou presumivelmente novo&#8221; ainda constava nas diretrizes de IAMCSST como indica&#231;&#227;o para cateterismo emergencial. Como resultado, in&#250;meros pacientes foram encaminhados ao laborat&#243;rio de hemodin&#226;mica apenas com base em dor tor&#225;cica associada ao BRE, e o pr&#243;prio achado ECG foi, por vezes, aceito como diagn&#243;stico de IAM &#8212; um exemplo cl&#225;ssico de vi&#233;s de incorpora&#231;&#227;o.<sup><xref ref-type="bibr" rid="B78">78</xref></sup> Segundo, &#233; necess&#225;rio reconhecer um prov&#225;vel vi&#233;s de investiga&#231;&#227;o<sup><xref ref-type="bibr" rid="B79">79</xref></sup> de efeito oposto: apenas pacientes considerados suficientemente graves &#8212; ou atendidos em centros com estrat&#233;gia invasiva preferencial &#8212; foram submetidos &#224; angiografia ou &#224; coleta seriada de biomarcadores. Assim, algumas oclus&#245;es verdadeiras, tanto no grupo com BRE quanto no grupo sem BRE, podem n&#227;o ter sido submetidas ao teste de refer&#234;ncia. Em s&#237;ntese, os dados n&#227;o sustentam a ativa&#231;&#227;o rotineira do laborat&#243;rio de hemodin&#226;mica com base apenas na presen&#231;a de BRE. Esses achados evidenciam como protocolos de ativa&#231;&#227;o guiados por diretrizes podem gerar um n&#250;mero substancial de &#8220;falsos positivos&#8221;, ao mesmo tempo em que deixam de identificar oclus&#245;es silenciosas em pacientes sem BRE.</p>
      <p>Nosso objetivo principal foi avaliar a acur&#225;cia diagn&#243;stica do BRE definitivamente novo ou presumivelmente novo na identifica&#231;&#227;o de IAM. Embora muitos cl&#237;nicos j&#225; tenham atendido pacientes com BRE durante um epis&#243;dio de IAM, sua utilidade diagn&#243;stica precisa ser definida com base em estudos de acur&#225;cia &#8212; por meio da constru&#231;&#227;o de tabelas de conting&#234;ncia, compara&#231;&#227;o entre casos e controles e c&#225;lculo de verdadeiros e falsos positivos e negativos. Para refletir a tomada de decis&#227;o cl&#237;nica na pr&#225;tica &#8212; na qual m&#233;dicos, frequentemente influenciados por diretrizes desatualizadas, podem buscar ECGs pr&#233;vios &#8212; conduzimos duas an&#225;lises paralelas: em uma, o BRE indeterminado foi considerado como &#8220;presumivelmente novo&#8221;; na outra, como &#8220;antigo&#8221;. As sensibilidades e especificidades resultantes geraram LRs que oferecem informa&#231;&#245;es relevantes. Em ambas as an&#225;lises, LR+ e LR&#8722; foram pr&#243;ximos de 1,0, sugerindo que identificar um BRE definitivamente novo ou presumivelmente novo n&#227;o altera de forma significativa a probabilidade de IAM em compara&#231;&#227;o a um BRE antigo. Al&#233;m disso, os IC 95% para LR+, LR&#8722; e para a DOR cruzaram o valor nulo de 1,0, indicando incerteza estat&#237;stica consider&#225;vel. De fato, alguns dados sugerem at&#233; uma poss&#237;vel correla&#231;&#227;o inversa entre BRE novo e a ocorr&#234;ncia de IAM.<sup><xref ref-type="bibr" rid="B80">80</xref></sup> A observa&#231;&#227;o de que os ICs tanto da DOR quanto da LR+ incluem o valor 1,0 implica insuficiente evid&#234;ncia estat&#237;stica para concluir que a presen&#231;a de um BRE novo ou presumivelmente novo aumente &#8212; ou reduza &#8212; de forma significativa a probabilidade de IAM.<sup><xref ref-type="bibr" rid="B81">81</xref></sup> Uma DOR ou uma LR+ cujo intervalo de confian&#231;a inclua o valor 1,0 indica aus&#234;ncia de confian&#231;a estat&#237;stica suficiente para concluir se a presen&#231;a de um BRE novo ou presumivelmente novo aumenta ou diminui de forma significativa a probabilidade de IAM. Portanto, distinguir BRE novo de antigo com base exclusivamente na cronologia do ECG n&#227;o fornece informa&#231;&#245;es clinicamente &#250;teis para a tomada de decis&#227;o em pacientes que se apresentam ao pronto-socorro com dor tor&#225;cica. Em termos pr&#225;ticos, isso sugere que, no cen&#225;rio agudo, a distin&#231;&#227;o entre BRE novo e antigo carece tanto de relev&#226;ncia cl&#237;nica quanto de valor diagn&#243;stico. A cronologia n&#227;o acrescenta nenhuma informa&#231;&#227;o diagn&#243;stica significativa.</p>
      <p>Tamb&#233;m avaliamos crit&#233;rios ECGs consagrados para o diagn&#243;stico de IAM na presen&#231;a de BRE, com foco na identifica&#231;&#227;o de sinais isqu&#234;micos como ferramenta para orientar a tomada de decis&#227;o cl&#237;nica. Nossas an&#225;lises destacaram o valor diagn&#243;stico dos crit&#233;rios de Sgarbossa e dos MSC, especialmente por seus altos valores de LR+, que refletem grande potencial confirmat&#243;rio quando presentes. Em uma an&#225;lise de sensibilidade restrita a estudos que definiram IAM com base em confirma&#231;&#227;o angiogr&#225;fica, os MSC demonstraram desempenho especialmente robusto. Essa abordagem refinada apresentou uma LR+ de 11,337 e uma LR&#8722; de 0,177, superando outros crit&#233;rios ECGs tanto na confirma&#231;&#227;o quanto na exclus&#227;o de eventos coronarianos oclusivos.</p>
      <p>Em uma an&#225;lise baseada no paradigma OMI-NOMI,<sup><xref ref-type="bibr" rid="B82">82</xref>,<xref ref-type="bibr" rid="B83">83</xref></sup> que define IAM com base na presen&#231;a de oclus&#245;es confirmadas por angiografia, apenas o estudo de Wegmann et al.<sup><xref ref-type="bibr" rid="B63">63</xref></sup> utilizou a OCA como padr&#227;o-ouro ao avaliar o valor diagn&#243;stico da cronologia do BRE. Esse estudo relatou uma sensibilidade de 37,5%, especificidade de 67,39%, LR+ de 1,15 e LR&#8722; de 0,93. Esses valores indicam que classificar o BRE como novo ou antigo n&#227;o oferece valor diagn&#243;stico clinicamente nem estatisticamente relevante para identificar OMI &#8212; achado consistente com o conjunto mais amplo de evid&#234;ncias. Em contraste, cinco estudos utilizaram a OMI como desfecho ou padr&#227;o de refer&#234;ncia na avalia&#231;&#227;o dos crit&#233;rios de Sgarbossa e dos MSC, conferindo maior solidez metodol&#243;gica e relev&#226;ncia cl&#237;nica a esses instrumentos baseados no ECG. Tanto os crit&#233;rios originais quanto os modificados demonstraram desempenho diagn&#243;stico superior, com LR+ significativamente mais altas e LR&#8722; mais baixas, alterando de forma significativa a probabilidade p&#243;s-teste da doen&#231;a e refor&#231;ando sua utilidade cl&#237;nica na identifica&#231;&#227;o de OCA.</p>
      <p>Tamb&#233;m avaliamos a acur&#225;cia diagn&#243;stica dos Crit&#233;rios de Barcelona. No entanto, a validade dessa abordagem tem sido questionada devido a limita&#231;&#245;es metodol&#243;gicas &#8212; especialmente quanto aos crit&#233;rios de sele&#231;&#227;o e ao padr&#227;o de refer&#234;ncia adotado, que define IAM com base na presen&#231;a de qualquer les&#227;o angiogr&#225;fica acompanhada de eleva&#231;&#227;o de troponina.<sup><xref ref-type="bibr" rid="B84">84</xref></sup> Essas limita&#231;&#245;es levantam d&#250;vidas sobre a confiabilidade dos achados. Tal fragilidade metodol&#243;gica &#233; refor&#231;ada pelo alto risco de vi&#233;s identificado na avalia&#231;&#227;o pelo instrumento QUADAS-2 (Material Suplementar 1). Assim, o desempenho diagn&#243;stico dos Crit&#233;rios de Barcelona deve ser interpretado com cautela, sendo necess&#225;rios novos estudos prospectivos para validar sua aplicabilidade cl&#237;nica.</p>
      <p>Nosso estudo refor&#231;a de forma contundente a utilidade cl&#237;nica da avalia&#231;&#227;o ativa de sinais isqu&#234;micos em pacientes com BRE, por meio dos crit&#233;rios de Sgarbossa ou dos MSC. Essa estrat&#233;gia oferece valor estat&#237;stico e cl&#237;nico significativamente superior &#224; tentativa de determinar se o BRE &#233; novo ou antigo &#8212; uma distin&#231;&#227;o que se mostrou sem valor diagn&#243;stico (<xref ref-type="fig" rid="f01">Figura Central</xref>). A prioriza&#231;&#227;o de crit&#233;rios ECG isqu&#234;micos est&#225; mais alinhada com as necessidades cl&#237;nicas e aprimora a acur&#225;cia diagn&#243;stica na avalia&#231;&#227;o de OCA.</p>
      <sec>
        <title>Limita&#231;&#245;es do estudo</title>
        <p>Algumas limita&#231;&#245;es deste estudo devem ser reconhecidas. Em primeiro lugar, houve heterogeneidade consider&#225;vel nas defini&#231;&#245;es e nos crit&#233;rios diagn&#243;sticos tanto para o BRE quanto para o IAM entre os estudos inclu&#237;dos, refletindo mudan&#231;as nas pr&#225;ticas cl&#237;nicas ao longo do tempo. Essa variabilidade pode ter influenciado tanto as estimativas de preval&#234;ncia quanto os desfechos de acur&#225;cia diagn&#243;stica em nossa metan&#225;lise. Em segundo lugar, nossa an&#225;lise da mortalidade intra-hospitalar baseou-se em dados n&#227;o ajustados, uma vez que estimativas ajustadas n&#227;o foram consistentemente reportadas nos estudos. Como consequ&#234;ncia, nossos achados podem n&#227;o considerar integralmente potenciais fatores de confus&#227;o, como comorbidades ou diferen&#231;as nas estrat&#233;gias terap&#234;uticas. Assim, os leitores devem interpretar essas estimativas de mortalidade com cautela, reconhecendo que outras vari&#225;veis cl&#237;nicas n&#227;o capturadas pela an&#225;lise podem influenciar os desfechos. Em terceiro lugar, embora tenhamos adotado uma metodologia rigorosa e seguido diretrizes consolidadas para revis&#245;es sistem&#225;ticas, n&#227;o &#233; poss&#237;vel descartar completamente a possibilidade de exclus&#227;o de estudos relevantes. Apesar de nossos esfor&#231;os para realizar uma busca ampla, publica&#231;&#245;es pertinentes &#8212; especialmente aquelas n&#227;o indexadas nas bases de dados selecionadas ou publicadas em outros idiomas &#8212; podem ter sido inadvertidamente omitidas. Por fim, a validade de nossos resultados est&#225;, inevitavelmente, condicionada &#224; qualidade dos estudos inclu&#237;dos. Como ocorre em qualquer metan&#225;lise, a solidez de nossas conclus&#245;es depende diretamente do rigor metodol&#243;gico e dos padr&#245;es de relato das fontes prim&#225;rias de dados.</p>
      </sec>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclus&#227;o</title>
      <p>Nossa an&#225;lise abrangente corrobora as diretrizes atuais que deixaram de considerar o BRE &#8212; independentemente de sua cronologia &#8212; como equivalente direto ao IAM. A aplica&#231;&#227;o de crit&#233;rios ECG espec&#237;ficos para identificar sinais isqu&#234;micos em pacientes com BRE melhora tanto a acur&#225;cia diagn&#243;stica quanto a tomada de decis&#245;es cl&#237;nicas. Nesse contexto, os MSC se destacam como uma ferramenta diagn&#243;stica confi&#225;vel e eficaz. Esses achados contribuem de forma significativa para o panorama em transforma&#231;&#227;o da pr&#225;tica cardiol&#243;gica e ressaltam a import&#226;ncia de uma abordagem mais racional e baseada em evid&#234;ncias na avalia&#231;&#227;o da s&#237;ndrome coronariana aguda suspeita. Este estudo tem potencial para influenciar futuras revis&#245;es de diretrizes que ainda tratam o BRE novo ou presumivelmente novo como indicativo de oclus&#227;o coronariana aguda, al&#233;m de orientar a pr&#225;tica cl&#237;nica ao desencorajar a manuten&#231;&#227;o de pressupostos diagn&#243;sticos ultrapassados.</p>
    </sec>
    <sec id="sec1" sec-type="supplementary-material">
      <title>Supplementary Materials</title>
      <supplementary-material id="suppl1">
        <label>*Material suplementar</label>
        <p>Material suplementar: Para informa&#231;&#227;o adicional, por favor, clique aqui. <ext-link ext-link-type="uri" xlink:href="https://abccardiol.org/supplementary-material/2025/12210/2025-0109_AO_Supplemental_Material.pdf">https://abccardiol.org/supplementary-material/2025/12210/2025-0109_AO_Supplemental_Material.pdf</ext-link> </p>
        <media mime-subtype="pdf" mimetype="application" xlink:href="https://minio.scielo.br/documentstore/1678-4170/84p7MNSrypxktHchfh4jQTk/e16360705d1734baa3fd06cdf05c183557481cb4.pdf"/>
      </supplementary-material>
    </sec>
  </body>
  <back>
    <ref-list>
      <title>Refer&#234;ncias</title>
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          <article-title>From ST-Segment Elevation MI to Occlusion MI: The New Paradigm Shift in Acute Myocardial Infarction</article-title>
          <source>JACC Adv</source>
          <year>2024</year>
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            <etal>et al</etal>
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    </ref-list>
    <fn-group>
      <fn fn-type="other">
        <label>Vincula&#231;&#227;o acad&#234;mica:</label>
        <p> N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
      </fn>
      <fn fn-type="other">
        <label>Aprova&#231;&#227;o &#233;tica e consentimento informado:</label>
        <p> Este artigo n&#227;o cont&#233;m estudos com humanos ou animais realizados por nenhum dos autores.</p>
      </fn>
      <fn fn-type="other">
        <label>Uso de Intelig&#234;ncia Artificial:</label>
        <p> Os autores n&#227;o utilizaram ferramentas de intelig&#234;ncia artificial no desenvolvimento deste trabalho.</p>
      </fn>
      <fn fn-type="data-availability" specific-use="data-available-upon-request">
        <label>Disponibilidade de Dados:</label>
        <p> Todo o conjunto de dados que d&#225; suporte aos resultados deste estudo est&#225; dispon&#237;vel mediante solicita&#231;&#227;o ao autor correspondente.</p>
      </fn>
      <fn fn-type="financial-disclosure">
        <label>Fontes de financiamento:</label>
        <p> O presente estudo n&#227;o teve fontes de financiamento externas.</p>
      </fn>
    </fn-group>
  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-id pub-id-type="doi">10.36660/abc.20250109i</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Accuracy of Left Bundle Branch Block Chronology and Electrocardiography Criteria for Acute Myocardial Infarction Diagnosis: A Systematic Review and Meta-analysis</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-3835-6067</contrib-id>
          <name>
            <surname>Alencar</surname>
            <given-names>Jos&#233; Nunes de</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Acquisition of data</role>
          <role>Analysis and interpretation of the data</role>
          <role>Statistical analysis and Writing of the manuscript</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lima</surname>
            <given-names>Gleydson Wesley Freire</given-names>
          </name>
          <role>Acquisition of data</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Geraldo</surname>
            <given-names>Haissa Assad dos Santos</given-names>
          </name>
          <role>Acquisition of data</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Fernandes</surname>
            <given-names>Rinaldo Carvalho</given-names>
          </name>
          <role>Acquisition of datar</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Scheffer</surname>
            <given-names>Matheus Kiszka</given-names>
          </name>
          <role>Acquisition of data</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Felicioni</surname>
            <given-names>Sandro Pinelli</given-names>
          </name>
          <role>Acquisition of data</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Marchi</surname>
            <given-names>Mariana Fuziy Nogueira De</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Acquisition of data</role>
          <role>Critical revision of the manuscript for content</role>
          <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">Instituto Dante Pazzanese de Cardiologia, S&#227;o Paulo, SP &#8211; Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c1001"><label>Mailing Address:</label> Jos&#233; Nunes de Alencar Neto &#8226; Instituto Dante Pazzanese de Cardiologia &#8211; Av. Dr. Dante Pazzanese, 500. CEP 04012-091, Vila Mariana, S&#227;o Paulo, SP &#8211; Brasil E-mail: <email>jose.alencar@dantepazzanese.org.br</email> </corresp>
        <fn fn-type="conflict">
          <label>Potential conflict of interest:</label>
          <p> No potential conflict of interest relevant to this article was reported.</p>
        </fn>
        <fn fn-type="edited-by">
          <label>Editor responsible for the review:</label>
          <p>Marcio Bittencourt</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background</title>
          <p> The diagnostic utility of new or presumed new left bundle branch block (LBBB) for acute myocardial infarction (AMI) in the setting of acute coronary syndrome (ACS) remains controversial.</p>
        </sec>
        <sec>
          <title>Objective</title>
          <p> To evaluate whether the timing of LBBB predicts AMI and to compare its diagnostic accuracy with ischemic electrocardiography (ECG) criteria, particularly the Modified Sgarbossa Criteria (MSC).</p>
        </sec>
        <sec>
          <title>Methods</title>
          <p> We searched PubMed and Scopus for studies involving patients with ACS with LBBB through December 2023. Sensitivity, specificity, positive (LR+) and negative (LR&#8211;) likelihood ratios, and diagnostic odds ratios (DOR) were calculated to assess diagnostic accuracy. Incidence and mortality data were also analyzed. Risk of bias was evaluated using the Newcastle-Ottawa Scale (NOS) and the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool.</p>
        </sec>
        <sec>
          <title>Results</title>
          <p> A total of 51 studies were included. LBBB occurred in 3.3% of ACS presentations and was associated with higher in-hospital mortality. Differentiating new from old LBBB was diagnostically neutral: LR+ 1.30 (95% CI: 0.75 to 1.85), LR&#8211; 0.90 (95% CI: 0.79 to 1.02), and DOR 1.44 (95% CI: 0.93 to 2.24); all confidence intervals crossed the null value of 1.0. In contrast, MSC demonstrated 83.6% sensitivity (95% CI: 55.4 to 95.5%) and 92.6% specificity (95% CI: 78.9 to 97.7%) for angiographically confirmed occlusive AMI, with LR+ 11.34 (95% CI: 3.67 to 34.99) and LR&#8211; 0.18 (95% CI: 0.054 to 0.575).</p>
        </sec>
        <sec>
          <title>Conclusion</title>
          <p> LBBB chronology alone does not significantly impact the likelihood of AMI. Ischemic ECG criteria &#8212; especially the MSC &#8212; provide substantially greater diagnostic accuracy and should guide clinical decision-making in ACS patients with LBBB.</p>
        </sec>
      </abstract>
      <abstract abstract-type="graphical">
        <p>
          <fig id="f01001">
            <label>Central Illustration:</label>
            <caption>
              <title>Accuracy of Left Bundle Branch Block Chronology and Electrocardiography Criteria for Acute Myocardial Infarction Diagnosis: A Systematic Review and Meta-analysis</title>
            </caption>
            <attrib>LBBB: left bundle branch block; DOR: diagnostic odds ratio; AMI: acute myocardial infarction due to occlusion; LR+: positive likelihood ratio; LR&#8211;: negative likelihood ratio; ACS: acute coronary syndrome.</attrib>
            <graphic xlink:href="1678-4170-abc-122-10-e20250109-50109-gf01-en.tif"/></fig>
        </p>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>Myocardial Infarction</kwd>
        <kwd>Electrocardiography</kwd>
        <kwd>Acute Coronary Syndrome</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>Patients presenting with suspected acute coronary syndrome (ACS) and left bundle branch block (LBBB) pose a complex clinical challenge. The presence of new or presumed new LBBB in this context has generated significant debate, particularly regarding its diagnostic and therapeutic implications. Whether new or presumably new LBBB should be considered an electrocardiographic (ECG) equivalent to ST-segment elevation myocardial infarction (STEMI) remains unclear, prompting further investigation into its clinical relevance.<sup><xref ref-type="bibr" rid="B1">1</xref></sup></p>
        <p>The 2004 guidelines from the American College of Cardiology (ACC) and the American Heart Association (AHA) initially recommended early reperfusion therapy &#8212; either fibrinolysis or percutaneous coronary intervention (PCI) &#8212; for patients with new or presumed new LBBB, assigning it a Class I indication.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> However, this strategy has faced increasing scrutiny due to the high rate of cardiac catheterizations in patients without an occluded culprit artery, raising concerns about the risks of unnecessary fibrinolytic treatment and invasive procedures.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
        <p>These evolving perspectives underscore the need to reassess the role of LBBB in the diagnosis and management of acute myocardial infarction (AMI).<sup><xref ref-type="bibr" rid="B4">4</xref></sup> The most recent ACC/AHA guidelines no longer recognize LBBB as an automatic STEMI equivalent.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> In contrast, the 2023 European guidelines recommend treating patients who present with LBBB and clinical features suggestive of ACS as STEMI cases, regardless of whether the conduction block is previously known.<sup><xref ref-type="bibr" rid="B6">6</xref></sup></p>
        <p>In addressing clinically relevant questions within a real-world context, this meta-analysis aimed to quantify the prevalence of LBBB among patients presenting with suspected ACS. Additionally, by analyzing mortality data, we investigated whether patients with LBBB experience higher mortality rates compared to those with other conduction abnormalities or ECG findings.</p>
        <p>We also evaluated whether the clear identification of new LBBB &#8212; or the ability to estimate its timing &#8212; serves as a reliable marker for AMI, as determined by elevated cardiac necrosis markers or angiographically confirmed acute coronary occlusion (ACO), in patients with suspected ACS. Finally, we assessed whether specific ECG criteria for ischemia in the setting of LBBB offer sufficient diagnostic accuracy for routine clinical use.</p>
        <p>This comprehensive analysis, conducted in accordance with Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA)<sup><xref ref-type="bibr" rid="B7">7</xref>,<xref ref-type="bibr" rid="B8">8</xref></sup> and Meta-analyses Of Observational Studies in Epidemiology (MOOSE)<sup><xref ref-type="bibr" rid="B9">9</xref></sup> guidelines, aims to provide a nuanced understanding of the role of LBBB in ACS and deliver meaningful insights to guide clinical decision-making.</p>
      </sec>
      <sec sec-type="methods">
        <title>Methods</title>
        <p>In this systematic review, we included studies involving patients with ACS or suspected ACS in the presence of new or presumed new LBBB, ischemic LBBB, or LBBB due to pacing. Our primary objective was to assess the diagnostic accuracy of new LBBB or LBBB with ischemic ECG criteria, comparing sensitivity and specificity against reference standards such as cardiac biomarkers (CK-MB or troponin) and coronary angiography.</p>
        <p>We also aimed to evaluate the prevalence and in-hospital mortality associated with LBBB in the context of ACS. Studies were included regardless of language and publication status, covering all records available from database inception through December 2023. The full search strategy is provided in Supplementary Material 1.</p>
        <p>Our search was conducted through December 2023 using the PubMed and Scopus databases. The search strategy was specifically designed to capture studies relevant to LBBB in the context of ACS. Full search strings are detailed in the supplementary materials. The strategy was refined with specific filters to match our eligibility criteria, focusing on publication status and study type to ensure relevance and accuracy.</p>
        <p>Two review authors (H.G. and G.L.) independently screened titles and abstracts. Discrepancies were resolved by a third review author (R.F.). Full-text screening was subsequently performed by two additional review authors (J.A. and M.M.). The screening process was managed using the HubMeta online tool.<sup><xref ref-type="bibr" rid="B10">10</xref></sup></p>
        <p>We applied strict exclusion criteria, omitting studies that focused on other conduction abnormalities, LBBB not related to acute ischemia, clinical guidelines, review articles, case reports, previous meta-analyses or systematic reviews, studies on chronic coronary disease, or those that addressed ACS without explicitly involving new or presumed new LBBB. Studies focusing on diagnostic methods other than resting ECG, as well as those addressing painful LBBB syndrome, were also excluded.</p>
        <sec>
          <title>Definitions of index test and outcomes</title>
          <p>LBBB was defined by a QRS duration &#8805; 120 ms and characteristic QRS morphology, including notching or slurring in the middle third of the QRS complex in at least two of the following leads: V1, V2, V5, V6, I, and aVL. Diagnostic criteria also included a delayed R-wave peak in V5&#8211;V6 exceeding 60 ms. In the horizontal plane, findings included a QS or rS pattern in V1 with ST-segment elevation (STE) and a positive, asymmetrical T wave, as well as a prominent R wave in V6 accompanied by a negative, asymmetrical T wave. When the QRS duration is less than 140 ms, the T wave in V6 may appear positive.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> However, due to the extended time span covered by this review, the definition of LBBB has evolved over the years. Therefore, we accepted the definition used by each study&#8217;s original investigators at the time of their research.</p>
          <p>Similarly, the definition of AMI has changed over time, incorporating different criteria. A biomarker-based diagnosis was generally accepted when there was an elevation in markers such as AST, ALT, CPK, CK-MB, or troponin. More recent studies adopted the universal definition of AMI, which includes ischemic ECG changes such as STE or new or presumed new LBBB.<sup><xref ref-type="bibr" rid="B12">12</xref>,<xref ref-type="bibr" rid="B13">13</xref></sup></p>
          <p>Another outcome evaluated was angiographically confirmed ACO, defined as the presence &#8212; or suspected presence &#8212; of an ACO on angiography. This is considered a surrogate composite outcome, typically involving a consistent clinical presentation, the presence of a coronary lesion, and markedly elevated troponin levels.<sup><xref ref-type="bibr" rid="B14">14</xref></sup> This more contemporary and precise definition was highlighted in the text whenever available.</p>
        </sec>
        <sec>
          <title>Statistical analysis</title>
          <p>For dichotomous outcomes such as prevalence and mortality, we performed random-effects meta-analyses using the Onlinemeta software (version 1.0: 2022.3.15).<sup><xref ref-type="bibr" rid="B15">15</xref></sup> Heterogeneity was assessed and illustrated using the Bayesian I<sup>2</sup> statistic,<sup><xref ref-type="bibr" rid="B16">16</xref></sup> with planned subgroup analyses based on population and methodological differences. High heterogeneity was defined as I<sup>2</sup> &gt; 75%.<sup><xref ref-type="bibr" rid="B17">17</xref></sup></p>
          <p>To assess potential publication bias, we used funnel plots along with Egger&#8217;s<sup><xref ref-type="bibr" rid="B18">18</xref></sup> and Begg&#8217;s<sup><xref ref-type="bibr" rid="B19">19</xref></sup> tests. A p-value &lt; 0.05 was considered indicative of significant publication bias. All related plots and tests are presented in Supplementary Material 1.</p>
          <p>For diagnostic test accuracy outcomes, we conducted a meta-analysis using the <italic>mada</italic> package in R, applying the bivariate Reitsma model.<sup><xref ref-type="bibr" rid="B20">20</xref>,<xref ref-type="bibr" rid="B21">21</xref></sup> We calculated pooled sensitivity, specificity, positive (LR+) and negative (LR&#8211;) likelihood ratios, and diagnostic odds ratios (DOR), each with 95% CIs estimated using the delta method.</p>
          <p>Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS)<sup><xref ref-type="bibr" rid="B22">22</xref></sup> for case-control studies and the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2)<sup><xref ref-type="bibr" rid="B23">23</xref></sup> for diagnostic accuracy studies. Visualizations were generated using the <italic>robvis</italic> online tool.<sup><xref ref-type="bibr" rid="B24">24</xref></sup></p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Results</title>
        <p>The electronic database search yielded 2,700 articles. After removing duplicates, 1,967 unique records remained for initial screening. Title and abstract screening narrowed the selection to 146 articles. Following a thorough full-text review, 51 studies met the inclusion criteria and were included in the meta-analysis.</p>
        <p>Details of the study selection process are presented in <xref ref-type="fig" rid="f02001">Figure 1</xref> in the Results section. The complete search strings and baseline characteristics of the included studies are provided in Supplementary Material 1.</p>
        <p>
          <fig id="f02001">
            <label>Figure 1</label>
            <caption>
              <title>&#8211; Flowchart of the study selection process from initial database search to the final inclusion of 51 studies in the meta-analysis.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-122-10-e20250109-50109-gf02-en.tif"/></fig>
        </p>
        <sec>
          <title>Prevalence of LBBB in ACS</title>
          <p>A subset of 29 studies investigated the prevalence of new, presumed new, or established LBBB among 221,261 consecutive cases with suspected ACS.<sup><xref ref-type="bibr" rid="B25">25</xref></sup> Substantial heterogeneity in ACS diagnosis was observed, with an I<sup>2</sup> statistic of 99%. Overall, 3.3% (95% CI: 2.7% to 4.1%) of ACS cases presented with LBBB, regardless of its chronology. A graphical summary of these findings is shown in <xref ref-type="fig" rid="f03001">Figure 2</xref>.</p>
          <p>
            <fig id="f03001">
              <label>Figure 2</label>
              <caption>
                <title>&#8211; Forest plot of the prevalence of LBBB among patients with ACS across 29 studies. Individual study estimates are shown with corresponding 95% CIs along with the overall pooled prevalence and heterogeneity statistics. ACS: acute coronary syndrome; LBBB: left bundle branch block.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-122-10-e20250109-50109-gf03-en.tif"/></fig>
          </p>
          <p>No significant publication bias was detected, as demonstrated by the funnel plot available in Supplementary Material 1.</p>
        </sec>
        <sec>
          <title>In-hospital mortality of LBBB in ACS</title>
          <p>To assess in-hospital mortality among ACS patients, we conducted a random-effects meta-analysis of 14 studies involving 418,417 individuals presenting with chest pain.<sup><xref ref-type="bibr" rid="B27">27</xref>-<xref ref-type="bibr" rid="B29">29</xref>,<xref ref-type="bibr" rid="B32">32</xref>,<xref ref-type="bibr" rid="B34">34</xref>,<xref ref-type="bibr" rid="B39">39</xref>,<xref ref-type="bibr" rid="B42">42</xref>,<xref ref-type="bibr" rid="B44">44</xref>,<xref ref-type="bibr" rid="B45">45</xref>,<xref ref-type="bibr" rid="B49">49</xref>,<xref ref-type="bibr" rid="B54">54</xref>-<xref ref-type="bibr" rid="B57">57</xref></sup> The presence of LBBB did not result in a significantly higher mortality rate when compared to right bundle branch block (RBBB). However, comparisons between patients with LBBB and those with STEMI or with normal QRS complexes without STE revealed significantly increased unadjusted ORs.</p>
          <p>Two studies specifically compared mortality between new and old LBBB. Of these, only one used angiographically confirmed ACO to define AMI.<sup><xref ref-type="bibr" rid="B39">39</xref></sup> Detailed results and data distributions are presented in <xref ref-type="fig" rid="f04001">Figure 3</xref>.</p>
          <p>
            <fig id="f04001">
              <label>Figure 3</label>
              <caption>
                <title>&#8211; Forest plots of unadjusted ORs for in-hospital mortality in patients with ACS across different ECG presentations. First box: Comparison between LBBB and RBBB shows no significant heterogeneity (I2 = 19%). Second box: Comparison between LBBB and ST-elevation myocardial infarction (STEMI) also shows no significant heterogeneity. Third box: Comparison between LBBB and patients without BBB demonstrates high heterogeneity (I2 = 87%). Fourth box: Comparison between nLBBB and oLBBB, with heterogeneity not assessed. Each plot displays individual study estimates with 95% CIs and overall pooled ORs, highlighting the variability in mortality outcomes according to ECG findings at presentation. ACS: acute coronary syndrome; BBB: bundle branch block; ECG: electrocardiography; LBBB: left BBB; nLBBB: new LBBB; oLBBB: old LBBB; RBBB: right bundle branch block; STEMI: ST-elevation myocardial infarction.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-122-10-e20250109-50109-gf04-en.tif"/></fig>
          </p>
        </sec>
        <sec>
          <title>OR of LBBB for AMI</title>
          <p>We analyzed the association between LBBB and the occurrence of angiographically confirmed ACO or biomarker-based AMI. Studies comparing these outcomes in patients with and without LBBB were pooled for analysis.<sup><xref ref-type="bibr" rid="B30">30</xref>,<xref ref-type="bibr" rid="B34">34</xref>,<xref ref-type="bibr" rid="B36">36</xref>,<xref ref-type="bibr" rid="B37">37</xref>,<xref ref-type="bibr" rid="B39">39</xref>,<xref ref-type="bibr" rid="B44">44</xref>,<xref ref-type="bibr" rid="B51">51</xref>,<xref ref-type="bibr" rid="B58">58</xref>-<xref ref-type="bibr" rid="B60">60</xref></sup> ORs were calculated using a random-effects model to estimate the strength of association across studies.</p>
          <p>For studies using angiography to confirm ACO, the pooled OR was 0.226 (95% CI: 0.092 to 0.557). For those using biomarker-based definitions, the pooled OR was 0.496 (95% CI: 0.358 to 0.689). The pooled overall OR across all studies was 0.336 (95% CI: 0.210 to 0.538), with Tau<sup>2</sup> = 0.443 and I<sup>2</sup> = 89%, indicating substantial heterogeneity.</p>
          <p>These findings are summarized in <xref ref-type="fig" rid="f05001">Figure 4</xref>. Funnel plots and publication bias assessments are presented in Supplementary Material 1.</p>
          <p>
            <fig id="f05001">
              <label>Figure 4</label>
              <caption>
                <title>&#8211; Forest plot of ORs for LBBB in predicting angiographically confirmed ACO and biomarker-based AMI. ACO: acute coronary occlusion; AMI: acute myocardial infarction; LBBB: left bundle branch block.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-122-10-e20250109-50109-gf05-en.tif"/></fig>
          </p>
        </sec>
        <sec>
          <title>Diagnostic test accuracy of new/presumably new LBBB</title>
          <p>In studies evaluating the diagnostic accuracy of clearly new LBBB compared to old or indeterminate blocks,<sup><xref ref-type="bibr" rid="B36">36</xref>,<xref ref-type="bibr" rid="B40">40</xref>,<xref ref-type="bibr" rid="B61">61</xref>-<xref ref-type="bibr" rid="B65">65</xref></sup> a total of 1,229 patients were analyzed. The pooled sensitivity was 0.321 (95% CI: 0.240 to 0.402), specificity was 0.753 (95% CI: 0.612 to 0.894), LR+ was 1.30 (95% CI: 0.751 to 1.850), and LR&#8211; was 0.902 (95% CI: 0.786 to 1.017). The DOR was 1.442 (95% CI: 0.927 to 2.243), with all confidence intervals crossing the threshold of 1.0, indicating no meaningful discriminative power.</p>
          <p>When indeterminate blocks were grouped together with new LBBB and compared against old LBBB in 848 patients,<sup><xref ref-type="bibr" rid="B40">40</xref>,<xref ref-type="bibr" rid="B61">61</xref>,<xref ref-type="bibr" rid="B62">62</xref>,<xref ref-type="bibr" rid="B64">64</xref></sup> the sensitivity was 0.633 (95% CI: 0.376 to 0.891), specificity 0.386 (95% CI: 0.326 to 0.446), LR+ 1.032 (95% CI: 0.653 to 1.411), and LR&#8211; 0.949 (95% CI: 0.343 to 1.556). The resulting DOR was 1.087 (95% CI: 0.520 to 2.271), again suggesting no significant diagnostic value.</p>
          <p>Only one study<sup><xref ref-type="bibr" rid="B63">63</xref></sup> used angiographically confirmed ACO as the reference standard for AMI, reporting a sensitivity of 37.5% and specificity of 67.39%. Additional details are provided in <xref ref-type="table" rid="t1001">Table 1</xref> and <xref ref-type="fig" rid="f06001">Figure 5</xref>.</p>
          <p>
            <table-wrap id="t1001">
              <label>Table 1</label>
              <caption>
                <title>&#8211; Diagnostic test accuracy of LBBB chronology in identifying AMI. Comparison of new vs. indeterminate or old LBBB, and new or indeterminate vs. old LBBB, including sensitivity, specificity, and likelihood ratios based on patient-level data</title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead>
                  <tr>
                    <th align="left">Strategy</th>
                    <th>n</th>
                    <th>Sensitivity (95% CI)</th>
                    <th>Specificity (95% CI)</th>
                    <th>LR+ (95% CI)</th>
                    <th>LR&#8211; (95% CI)</th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td>New LBBB vs. Indeterminate and old LBBB</td>
                    <td align="center">1,229</td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.321</p>
                        </list-item>
                        <list-item>
                          <p>(0.240 to 0.402)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.753</p>
                        </list-item>
                        <list-item>
                          <p>(0.612 to 0.894)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>1.3</p>
                        </list-item>
                        <list-item>
                          <p>(0.751 to 1.850)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.902</p>
                        </list-item>
                        <list-item>
                          <p>(0.786 to 1.017)</p>
                        </list-item>
                      </list>
                    </td>
                  </tr>
                  <tr>
                    <td>New or Indeterminate LBBB vs. old LBBB</td>
                    <td align="center">848</td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.633</p>
                        </list-item>
                        <list-item>
                          <p>(0.376 to 0.891)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.386</p>
                        </list-item>
                        <list-item>
                          <p>(0.326 to 0.446)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>1.032</p>
                        </list-item>
                        <list-item>
                          <p>(0.653 to 1.411)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.949</p>
                        </list-item>
                        <list-item>
                          <p>(0.343 to 1.556)</p>
                        </list-item>
                      </list>
                    </td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN1001">
                  <p>LBBB: left bundle branch block.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </p>
          <p>
            <fig id="f06001">
              <label>Figure 5</label>
              <caption>
                <title>&#8211; Forest plots showing pooled sensitivity and specificity with 95% CIs for two diagnostic comparisons involving LBBB chronology. Top panels: Comparison between new or presumably new LBBB and indeterminate or old LBBB. Bottom panels: Comparison between new or indeterminate LBBB and old LBBB. Both analyses were conducted in patients presenting with chest pain and evaluated for angiographically confirmed ACO or biomarker-based AMI. ACO: acute coronary occlusion; AMI: acute myocardial infarction; LBBB: left bundle branch block.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-122-10-e20250109-50109-gf06-en.tif"/></fig>
          </p>
        </sec>
        <sec>
          <title>Diagnostic test accuracy of ECG criteria</title>
          <p>This review also evaluated the diagnostic performance of established ECG criteria for AMI. These criteria, widely cited in the literature, were analyzed for their sensitivity and specificity in detecting biomarker-based or angiographically confirmed occlusive myocardial infarction (OMI). A summary of the findings is presented in <xref ref-type="table" rid="t2001">Table 2</xref>. Forest plots and QUADAS-based risk of bias assessments are available in Supplementary Material 1.</p>
          <p>
            <table-wrap id="t2001">
              <label>Table 2</label>
              <caption>
                <title>&#8211; Comparative diagnostic accuracy of ECG criteria for AMI in patients with LBBB. Sensitivity, specificity, and likelihood ratios (LR+ and LR&#8211;) are shown for the Sgarbossa criteria, MSC, Barcelona Criteria, and Chapman&#8217;s sign</title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead>
                  <tr>
                    <th align="left">Criteria/Sign</th>
                    <th>n</th>
                    <th style="font-weight:normal">Sensitivity (95% CI)</th>
                    <th style="font-weight:normal">Specificity (95% CI)</th>
                    <th>LR+ (95% CI)</th>
                    <th>LR&#8211; (95% CI)</th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td>Sgarbossa Criteria</td>
                    <td align="center">2,427</td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.404</p>
                        </list-item>
                        <list-item>
                          <p>(0.227 to 0.610)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.967</p>
                        </list-item>
                        <list-item>
                          <p>(0.922 to 0.987)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>12.384</p>
                        </list-item>
                        <list-item>
                          <p>(5.426 to 28.265)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.616</p>
                        </list-item>
                        <list-item>
                          <p>(0.445 to 0.854)</p>
                        </list-item>
                      </list>
                    </td>
                  </tr>
                  <tr>
                    <td>Sgarbossa &#8211; ACO</td>
                    <td align="center">1,369</td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.426</p>
                        </list-item>
                        <list-item>
                          <p>(0.305 to 0.557)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.962</p>
                        </list-item>
                        <list-item>
                          <p>(0.859 to 0.991)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>11.315</p>
                        </list-item>
                        <list-item>
                          <p>(2.677 to 47.825)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.596</p>
                        </list-item>
                        <list-item>
                          <p>(0.471 to 0.754)</p>
                        </list-item>
                      </list>
                    </td>
                  </tr>
                  <tr>
                    <td>MSC</td>
                    <td align="center">1,702</td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.688</p>
                        </list-item>
                        <list-item>
                          <p>(0.362 to 0.895)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.920</p>
                        </list-item>
                        <list-item>
                          <p>(0.841 to 0.961)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>8.576</p>
                        </list-item>
                        <list-item>
                          <p>(3.952 to 18.608)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.340</p>
                        </list-item>
                        <list-item>
                          <p>(0.135 to 0.857)</p>
                        </list-item>
                      </list>
                    </td>
                  </tr>
                  <tr>
                    <td>Modified Sgarbossa &#8211; ACO</td>
                    <td align="center">1,161</td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.836</p>
                        </list-item>
                        <list-item>
                          <p>(0.554 to 0.955)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.926</p>
                        </list-item>
                        <list-item>
                          <p>(0.789 to 0.977)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>11.337</p>
                        </list-item>
                        <list-item>
                          <p>(3.672 to 34.999)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.177</p>
                        </list-item>
                        <list-item>
                          <p>(0.054 to 0.575)</p>
                        </list-item>
                      </list>
                    </td>
                  </tr>
                  <tr>
                    <td>Barcelona Criteria</td>
                    <td align="center">887</td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.818</p>
                        </list-item>
                        <list-item>
                          <p>(0.403 to 0.968)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.868</p>
                        </list-item>
                        <list-item>
                          <p>(0.790 to 0.919)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>6.182</p>
                        </list-item>
                        <list-item>
                          <p>(2.815 to 13.577)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.210</p>
                        </list-item>
                        <list-item>
                          <p>(0.042 to 1.049)</p>
                        </list-item>
                      </list>
                    </td>
                  </tr>
                  <tr>
                    <td>Chapman&#8217;s sign</td>
                    <td align="center">104</td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.190</p>
                        </list-item>
                        <list-item>
                          <p>(0.108 to 0.311)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.870</p>
                        </list-item>
                        <list-item>
                          <p>(0.739 to 0.940)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>1.454</p>
                        </list-item>
                        <list-item>
                          <p>(0.582 to 3.635)</p>
                        </list-item>
                      </list>
                    </td>
                    <td align="center">
                      <list list-type="simple">
                        <list-item>
                          <p>0.932</p>
                        </list-item>
                        <list-item>
                          <p>(0.788 to 1.102)</p>
                        </list-item>
                      </list>
                    </td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN2001">
                  <p>ACO: acute coronary occlusion; AMI: acute myocardial infarction; ECG: electrocardiography; LBBB: left bundle branch block; MSC: Modified Sgarbossa Criteria.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </p>
          <p>The Modified Sgarbossa Criteria (MSC), developed to diagnose AMI in patients with LBBB, include concordant ST elevation &gt;1 mm in leads with a positive QRS complex (score 5); concordant ST depression &gt;1 mm in leads V1&#8211;V3 (score 3); and excessively discordant ST elevation &gt;5 mm in leads with a negative QRS complex (score 2). A total score of &#8805;3 is considered diagnostic.<sup><xref ref-type="bibr" rid="B66">66</xref></sup></p>
          <p>Applied to 2,427 patients with LBBB, compared against those without AMI or angiographically confirmed ACO, the MSC demonstrated a sensitivity of 0.404 (95% CI: 0.227 to 0.610) and a specificity of 0.967 (95% CI: 0.922 to 0.987).<sup><xref ref-type="bibr" rid="B14">14</xref>,<xref ref-type="bibr" rid="B25">25</xref>,<xref ref-type="bibr" rid="B26">26</xref>,<xref ref-type="bibr" rid="B31">31</xref>,<xref ref-type="bibr" rid="B66">66</xref>-<xref ref-type="bibr" rid="B71">71</xref></sup></p>
          <p>In a sensitivity analysis restricted to studies that used angiographic confirmation of AMI and excluded those involving pacemaker patients, five studies comprising 1,369 patients yielded a LR+ of 11.315 and a LR&#8722; of 0.596.<sup><xref ref-type="bibr" rid="B14">14</xref>,<xref ref-type="bibr" rid="B25">25</xref>,<xref ref-type="bibr" rid="B26">26</xref>,<xref ref-type="bibr" rid="B67">67</xref>,<xref ref-type="bibr" rid="B71">71</xref></sup></p>
          <p>The MSC diagnose AMI in patients with LBBB based on the presence of any of the following findings: concordant ST elevation &#8805;1 mm in one or more leads; concordant ST depression &#8805;1 mm in leads V1&#8211;V3; or proportionally excessive discordant STE &#8805;1 mm in any lead, defined as &#8805;25% of the depth of the preceding S-wave.<sup><xref ref-type="bibr" rid="B14">14</xref></sup> Among 1,702 patients, these criteria demonstrated a sensitivity of 0.688 (95% CI: 0.362 to 0.895) and a specificity of 0.920 (95% CI: 0.841 to 0.961), with a LR+ of 8.576 (95% CI: 3.952 to 18.608) and a LR&#8722; of 0.340 (95% CI: 0.135 to 0.857).<sup><xref ref-type="bibr" rid="B14">14</xref>,<xref ref-type="bibr" rid="B31">31</xref>,<xref ref-type="bibr" rid="B53">53</xref>,<xref ref-type="bibr" rid="B67">67</xref>-<xref ref-type="bibr" rid="B69">69</xref>,<xref ref-type="bibr" rid="B71">71</xref></sup> When restricting the analysis to studies that used angiographically confirmed myocardial infarction as the reference standard and excluded pacemaker patients, four studies involving 1,161 patients yielded a sensitivity of 0.836 (95% CI: 0.554 to 0.955), specificity of 0.926 (95% CI: 0.789 to 0.977), LR+ of 11.337 (95% CI: 3.672 to 34.999), and LR&#8722; of 0.177 (95% CI: 0.054 to 0.575).<sup><xref ref-type="bibr" rid="B14">14</xref>,<xref ref-type="bibr" rid="B53">53</xref>,<xref ref-type="bibr" rid="B67">67</xref>,<xref ref-type="bibr" rid="B71">71</xref></sup></p>
          <p>The Barcelona Criteria define myocardial infarction in the presence of LBBB based on any of the following findings: concordant ST elevation &#8805;1 mm in any lead, concordant ST depression in any lead, or discordant ST deviation &#8805;1 mm in any lead where the R or S wave is &#8804;6 mm.<sup><xref ref-type="bibr" rid="B72">72</xref></sup> These criteria were evaluated in two studies comprising a total of 887 patients, compared against those with LBBB who did not meet the Barcelona Criteria for angiographically confirmed ACO.<sup><xref ref-type="bibr" rid="B67">67</xref>,<xref ref-type="bibr" rid="B72">72</xref></sup> The pooled sensitivity was 0.818 (95% CI: 0.403 to 0.968), and the specificity was 0.868 (95% CI: 0.790 to 0.919).</p>
          <p>The Chapman&#8217;s sign &#8212; defined by notching in the upstroke of the R wave in leads I, aVL, and V6<sup><xref ref-type="bibr" rid="B73">73</xref></sup> &#8212; was evaluated for its diagnostic utility in AMI based on biomarker confirmation in two studies from the 1980s, involving a total of 104 patients.<sup><xref ref-type="bibr" rid="B74">74</xref>,<xref ref-type="bibr" rid="B75">75</xref></sup> The pooled sensitivity was 0.190 (95% CI: 0.108 to 0.311), and specificity was 0.870 (95% CI: 0.739 to 0.940).</p>
        </sec>
      </sec>
      <sec sec-type="discussion">
        <title>Discussion</title>
        <p>Our detailed analysis found that LBBB was present in 3.3% (95% CI: 2.7% to 4.1%) of ACS presentations. Although this prevalence may appear modest, it warrants careful clinical consideration due to the potential for incorporation bias &#8212; a phenomenon in which the diagnostic criteria overlap between the index test and the reference standard.<sup><xref ref-type="bibr" rid="B76">76</xref>,<xref ref-type="bibr" rid="B77">77</xref></sup> In many studies, the presence of new or presumed new LBBB was itself considered diagnostic of ACS, which may have inflated the reported prevalence.</p>
        <p>Our analysis of in-hospital mortality in ACS cohorts suggests that LBBB and RBBB are statistically comparable in terms of associated mortality risk. The unadjusted OR for in-hospital mortality among patients with LBBB was 1.135 (95% CI: 0.975 to 1.322), indicating no significant difference compared to RBBB.</p>
        <p>Our findings challenge the prevailing notion that the presence of LBBB &#8212; regardless of its timing &#8212; should be treated as a de facto AMI requiring immediate reperfusion therapy. The pooled OR of 0.226 (95% CI: 0.092&#8211;0.557) suggests that LBBB alone does not inherently increase the likelihood of AMI. Even when using biomarker-based definitions &#8212; which are less precise indicators of infarction &#8212; the OR rises only to 0.496 (95% CI: 0.358&#8211;0.689), still insufficient to justify an elevated diagnostic suspicion of AMI. Interestingly, several primary studies included in our analysis inferred a high risk of AMI based solely on the absolute number of AMIs observed among patients with LBBB, without adequately comparing these findings to non-LBBB populations. This comparative approach was essential to arriving at a more accurate and nuanced interpretation. These pooled ORs must be considered in light of two key sources of bias. First, many of the included studies were conducted during a period when &#8220;new or presumed-new LBBB&#8221; was still listed in STEMI guidelines as an indication for emergent catheterization. As a result, numerous patients were taken to the catheterization lab based solely on chest pain and the presence of LBBB, with the same ECG finding sometimes being accepted as diagnostic of AMI &#8212; an example of classical incorporation bias.<sup><xref ref-type="bibr" rid="B78">78</xref></sup> Second, a likely counteracting work-up bias<sup><xref ref-type="bibr" rid="B79">79</xref></sup> must also be acknowledged: only patients deemed ill enough &#8212; or managed at centers favoring an invasive approach &#8212; were referred for angiography or had serial biomarkers collected. Consequently, some true occlusions in both LBBB and non-LBBB groups may not have undergone the reference test. Overall, data do not support routine activation of the catheterization lab based solely on the presence of LBBB. These findings underscore how guideline-driven activation protocols may result in a substantial number of &#8220;false positives&#8221; while still missing silent occlusions in patients without LBBB.</p>
        <p>Our primary objective was to assess the diagnostic accuracy of definitively new or presumed new LBBB in identifying AMI. While many clinicians have encountered patients with LBBB during an infarction, its diagnostic utility must be defined through accuracy studies &#8212; by constructing contingency tables, comparing cases and controls, and calculating true and false positives and negatives. To reflect real-world clinical decision-making &#8212; where physicians, often influenced by outdated guidelines, may seek prior ECGs &#8212; we conducted two parallel analyses. In one, indeterminate LBBB was treated as &#8220;presumably new&#8221;; in the other, as &#8220;old.&#8221; The resulting sensitivities and specificities generated likelihood ratios that offer meaningful insights. In both analyses, the LR+ and LR&#8722; were close to 1.0, suggesting that identifying a definitively new or presumably new LBBB does not meaningfully change the probability of infarction compared to an old block. Moreover, the 95% confidence intervals for LR+, LR&#8722;, and DOR all crossed the null value of 1.0, indicating considerable statistical uncertainty. In fact, some data even suggest a potential inverse correlation between new LBBB and the likelihood of AMI.<sup><xref ref-type="bibr" rid="B80">80</xref></sup> The observation that the confidence intervals for both DOR and LR+ include 1.0 implies insufficient statistical evidence to conclude that a new or presumably new LBBB meaningfully increases &#8212; or decreases &#8212; the probability of AMI.<sup><xref ref-type="bibr" rid="B81">81</xref></sup> A DOR or LR+ that includes 1.0 in its confidence interval implies insufficient statistical confidence to conclude whether the presence of a new or presumably new LBBB meaningfully increases or decreases the probability of AMI. Therefore, distinguishing between new and old LBBB based solely on ECG chronology does not provide clinically useful information for decision-making in patients presenting to the emergency department with chest pain. In practical terms, this suggests that in the acute setting, the distinction between new and old LBBB lacks both clinical relevance and diagnostic value. Chronology adds no meaningful diagnostic information.</p>
        <p>We also evaluated established ECG criteria for diagnosing AMI in the setting of LBBB, focusing on the presence of ischemic signs as a tool to guide clinical decision-making. Our analyses highlighted the diagnostic value of the Sgarbossa and MSC, particularly due to their high LR+, which reflect their strong confirmatory potential when positive. In a sensitivity analysis limited to studies that defined AMI angiographically, the MSC demonstrated especially strong performance. This refined approach yielded a higher LR+ of 11.337 and a lower LR&#8722; of 0.177, outperforming other ECG criteria in both confirming and excluding occlusive coronary artery events.</p>
        <p>In an analysis framed within the OMI-NOMI paradigm,<sup><xref ref-type="bibr" rid="B82">82</xref>,<xref ref-type="bibr" rid="B83">83</xref></sup> which defines myocardial infarction based on angiographically confirmed occlusions, only Wegmann et al.<sup><xref ref-type="bibr" rid="B63">63</xref></sup> used angiographically confirmed ACO as the reference standard when evaluating the diagnostic value of LBBB chronology. That study reported a sensitivity of 37.5%, specificity of 67.39%, LR+ of 1.15, and LR&#8722; of 0.93. These likelihood ratios suggest that the classification of LBBB as new or old provides neither clinically nor statistically meaningful diagnostic information for identifying OMI &#8212; a finding consistent with the broader body of evidence. In contrast, five studies applied OMI as the outcome or reference standard when evaluating the Sgarbossa and MSC, thereby offering stronger methodological support and greater clinical relevance for these ECG-based tools. Both the original and modified criteria demonstrated superior diagnostic performance, with significantly higher LR+ and lower LR&#8722; values, meaningfully altering the post-test probability of disease and reinforcing their clinical utility in identifying ACO.</p>
        <p>We also evaluated the diagnostic accuracy of the Barcelona Criteria. However, the validity of this approach has been questioned due to methodological concerns &#8212; particularly its selection criteria and the reference standard, which defines myocardial infarction based on the presence of any angiographic lesion accompanied by troponin elevation.<sup><xref ref-type="bibr" rid="B84">84</xref></sup> These limitations raise concerns about the reliability of the findings. This is further reflected in the high risk of bias identified through the QUADAS-2 assessment (Supplementary Material 1). Consequently, the diagnostic performance of the Barcelona Criteria should be interpreted with caution, and new prospective studies are needed to validate its clinical utility.</p>
        <p>Our study strongly supports the clinical utility of actively assessing ischemic signs in patients with LBBB using the Sgarbossa or MSC. This strategy provides significantly greater statistical and clinical value than attempting to determine whether the LBBB is new or old &#8212; a distinction shown to be diagnostically uninformative (<xref ref-type="fig" rid="f01001">Central Illustration</xref>). Prioritizing ischemic ECG criteria aligns more closely with clinical imperatives and enhances diagnostic accuracy in the evaluation of ACO.</p>
        <sec>
          <title>Limitations of the study</title>
          <p>Several limitations of this study must be acknowledged. First, there was substantial heterogeneity in the definitions and diagnostic criteria for both LBBB and myocardial infarction across the included studies, reflecting changes in clinical practice over time. This variability may have influenced both the estimated prevalence and the diagnostic accuracy outcomes in our meta-analysis. Second, our analysis of in-hospital mortality relied on unadjusted data, as adjusted estimates were not consistently reported across studies. As a result, our findings may not fully account for potential confounders such as comorbidities or differences in treatment strategies. Readers should interpret these mortality estimates with caution, recognizing that other clinical variables not captured in the analysis may influence outcomes. Third, although we employed rigorous methodology and followed established systematic review guidelines, we cannot entirely exclude the possibility of missed studies. Despite our efforts to conduct a broad search, relevant publications &#8212; particularly those not indexed in the selected databases or published in other languages &#8212; may have been overlooked. Finally, the validity of our results is inherently dependent on the quality of the studies. As with any meta-analysis, the strength of our conclusions is shaped by the methodological rigor and reporting standards of the primary data sources.</p>
        </sec>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclusion</title>
        <p>Our comprehensive analysis supports current guidelines that no longer consider LBBB &#8212; regardless of its timing &#8212; as a direct equivalent of AMI. Applying specific ECG criteria to identify ischemic signs in patients with LBBB improves both diagnostic accuracy and clinical decision-making. In this context, the MSC stand out as a reliable and effective diagnostic tool. These findings contribute meaningfully to the evolving landscape of cardiac care and underscore the importance of a more rational and evidence-based approach in the evaluation of suspected ACS. This study has the potential to influence future guideline revisions that continue to treat new or presumed new LBBB as indicative of ACO, and to inform clinical practice by discouraging reliance on outdated diagnostic assumptions.</p>
      </sec>
      <sec id="sec1001" sec-type="supplementary-material">
        <title>Supplementary Materials</title>
        <supplementary-material id="suppl01-en">
          <label>*Supplemental Materials</label>
          <p>Supplemental Materials For additional information, please click here. <ext-link ext-link-type="uri" xlink:href="https://abccardiol.org/supplementary-material/2025/12210/2025-0109_AO_Supplemental_Material.pdf">https://abccardiol.org/supplementary-material/2025/12210/2025-0109_AO_Supplemental_Material.pdf</ext-link> </p>
          <media mime-subtype="pdf" mimetype="application" xlink:href="https://minio.scielo.br/documentstore/1678-4170/84p7MNSrypxktHchfh4jQTk/e16360705d1734baa3fd06cdf05c183557481cb4.pdf"/>
        </supplementary-material>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other">
          <label>Study association:</label>
          <p> This study is not associated with any thesis or dissertation work.</p>
        </fn>
        <fn fn-type="other">
          <label>Ethics approval and consent to participate:</label>
          <p> This article does not contain any studies with human participants or animals performed by any of the authors.</p>
        </fn>
        <fn fn-type="other">
          <label>Use of Artificial Intelligence:</label>
          <p> The authors did not use any artificial intelligence tools in the development of this work.</p>
        </fn>
        <fn fn-type="data-availability" specific-use="data-available-upon-request">
          <label>Data Availability:</label>
          <p> All datasets supporting the results of this study are available upon request from the corresponding author</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
