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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">WfyhJgGFdztftPTcLXtnLrJ</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2024000500401</article-id>
      <article-id pub-id-type="other">00401</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20230733</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo de Revis&#227;o</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Al&#233;m do Paradigma IAMCSST-IAMSSST: Proposta do Instituto Dante Pazzanese para o Diagn&#243;stico de Oclus&#227;o Coronariana Aguda</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>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>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Feres</surname>
            <given-names>Fausto</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 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 contrib-type="author">
          <name>
            <surname>Franchini</surname>
            <given-names>Kleber Gomes</given-names>
          </name>
          <role>Obten&#231;&#227;o de dados</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>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>Scheffer</surname>
            <given-names>Matheus Kiszka</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>Felicioni</surname>
            <given-names>Sandro Pinelli</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos 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>Costa</surname>
            <given-names>Ana Carolina Muniz</given-names>
          </name>
          <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>Fernandes</surname>
            <given-names>Rinaldo Carvalho</given-names>
          </name>
          <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">
          <contrib-id contrib-id-type="orcid">0000-0003-4108-4653</contrib-id>
          <name>
            <surname>Ramadan</surname>
            <given-names>Hugo Ribeiro</given-names>
          </name>
          <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>Meyers</surname>
            <given-names>Pendell</given-names>
          </name>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>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="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-9166-9804</contrib-id>
          <name>
            <surname>Smith</surname>
            <given-names>Stephen W.</given-names>
          </name>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>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="aff3">
            <sup>3</sup>
          </xref>
        </contrib>
        <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>
        <aff id="aff2">
          <label>2</label>
          <institution content-type="orgname">Carolinas Medical Center</institution>
          <institution content-type="orgdiv1">Department of Emergency Medicine</institution>
          <addr-line>
            <named-content content-type="city">Charlotte</named-content>
            <named-content content-type="state">NC</named-content>
          </addr-line>
          <country country="US">EUA</country>
          <institution content-type="original">Carolinas Medical Center &#8211; Department of Emergency Medicine, Charlotte, NC &#8211; EUA</institution>
        </aff>
        <aff id="aff3">
          <label>3</label>
          <institution content-type="orgname">Department of Emergency Medicine and University of Minnesota</institution>
          <institution content-type="orgdiv1">Hennepin Healthcare</institution>
          <addr-line>
            <named-content content-type="city">Minneapolis</named-content>
            <named-content content-type="state">MN</named-content>
          </addr-line>
          <country country="US">EUA</country>
          <institution content-type="original">Hennepin Healthcare, Department of Emergency Medicine and University of Minnesota, Minneapolis, MN &#8211; EUA</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><bold>Correspond&#234;ncia: Jos&#233; Nunes De Alencar &#8226;</bold> Instituto Dante Pazzanese de Cardiologia - Avenida Dr. Dante Pazzanese, 500. CEP <postal-code>04012-091</postal-code>, Vila Mariana, S&#227;o Paulo, SP - Brasil E-mail: <email>jose.alencar@dantepazzanese.org.br</email> </corresp>
        <fn fn-type="conflict">
          <label>Potencial conflito de interesse</label>
          <p>N&#227;o h&#225; conflito com o presente artigo</p>
        </fn>
        <fn fn-type="edited-by">
          <p>Editor respons&#225;vel pela revis&#227;o: Gl&#225;ucia Maria Moraes de Oliveira</p>
        </fn>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>15</day>
        <month>07</month>
        <year>2024</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <year>2024</year>
      </pub-date>
      <volume>121</volume>
      <issue>5</issue>
      <elocation-id>e20230733</elocation-id>
      <history>
        <date date-type="received">
          <day>25</day>
          <month>10</month>
          <year>2023</year>
        </date>
        <date date-type="rev-recd">
          <day>11</day>
          <month>01</month>
          <year>2024</year>
        </date>
        <date date-type="accepted">
          <day>13</day>
          <month>03</month>
          <year>2024</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Resumo</title>
        <p>Embora o modelo existente de classifica&#231;&#227;o do infarto agudo do mioc&#225;rdio (IAM) em IAMCSST e IAMSSST tenha sido ben&#233;fico, considera-se hoje que ele falha em abordar a complexidade das s&#237;ndromes coronarianas agudas.</p>
        <p>O estudo tem como objetivo examinar o atual paradigma IAMCSST-IAMSSST e defender um modelo mais detalhado, chamado de oclus&#227;o coronariana aguda (OCA) e Aus&#234;ncia de Oclus&#227;o Coron&#225;ria Aguda (NOCA), para um diagn&#243;stico e um manejo do IAM mais precisos.</p>
        <p>Realizou-se uma an&#225;lise abrangente da literatura m&#233;dica existente, com foco nas limita&#231;&#245;es do modelo IAMCSST-IAMSSST. O estudo tamb&#233;m descreve uma nova abordagem diagn&#243;stica para pacientes apresentando do tor&#225;cica nos departamentos de emerg&#234;ncia.</p>
        <p>O modelo IAMCSST-IAMSSST tradicional falha em prover um diagn&#243;stico preciso e um tratamento efetivo, principalmente na identifica&#231;&#227;o de oclus&#245;es da art&#233;ria coron&#225;ria. O modelo OCA-NOCA &#233; mais preciso em termos anat&#244;micos e fisiol&#243;gicos, e apoiado por pesquisa cl&#237;nica extensa e opini&#245;es de especialistas. Ele destaca a necessidade de r&#225;pida realiza&#231;&#227;o de eletrocardiogramas (ECGs) e terapias de reperfus&#227;o para casos suspeitos de OCA, visando melhorar os desfechos dos pacientes.</p>
        <p>O modelo OCA-NOCA abre um novo caminho para pesquisas e aplica&#231;&#245;es cl&#237;nicas futuras. Ele defende um entendimento mais abrangente dos mecanismos subjacentes das s&#237;ndromes coronarianas agudas, levando a planos individualizados de tratamentos. Espera-se que essa nova abordagem incite novos debates e pesquisas acad&#234;micas, principalmente na &#225;rea de cardiologia no Brasil, com o objetivo de aumentar a precis&#227;o diagn&#243;stica e a efic&#225;cia do tratamento de pacientes com IAM.</p>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave</title>
        <kwd>Eletrocardiografia</kwd>
        <kwd>Oclus&#227;o Coron&#225;ria</kwd>
        <kwd>Infarto do Mioc&#225;rdio</kwd>
      </kwd-group>
      <counts>
        <fig-count count="14"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="61"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>O diagn&#243;stico de infarto agudo do mioc&#225;rdio (IAM) est&#225; em um momento decisivo. O modelo IAMCSST-IAMSSST (infarto agudo do mioc&#225;rdio com supra de ST - infarto agudo do mioc&#225;rdio sem supra de ST) tem sido fundamental no direcionamento de tratamentos urgentes de reperfus&#227;o e na orienta&#231;&#227;o de profissionais m&#233;dicos para tratar eventos coron&#225;rios agudos. Embora o modelo tenha melhorado significativamente a sobrevida e a qualidade de vida do paciente, com o in&#237;cio da era da reperfus&#227;o no final do s&#233;culo passado, suas limita&#231;&#245;es em abordar as complexidades das doen&#231;as coron&#225;rias agudas t&#234;m sido cada vez mais evidentes.</p>
      <p>Neste artigo, n&#243;s, cardiologistas do Instituto Dante Pazzanese de Cardiologia, em colabora&#231;&#227;o com os proponentes originais deste paradigma, fazemos essa afirma&#231;&#227;o, tra&#231;ando paralelos entre os paradigmas atuais e mudan&#231;as seminais na literatura. Questionamos o paradigma IAMCSST-IAMSSST predominante no diagn&#243;stico de IAM, e defendemos o uso dos termos infarto do mioc&#225;rdio com oclus&#227;o, ou "oclus&#227;o coronariana aguda" (OCA) e aus&#234;ncia de oclus&#227;o coron&#225;ria aguda (NOCA). N&#243;s propomos este conceito como uma fundamenta&#231;&#227;o anat&#244;mica e fisiol&#243;gica mais precisa para o manejo e a classifica&#231;&#227;o do IAM. Defendemos fortemente essa nova perspectiva com base em uma extensa pesquisa cl&#237;nica, opini&#245;es de especialistas, e em nossa experi&#234;ncia cl&#237;nica. Nosso objetivo &#233; estimular discuss&#245;es cruciais na &#225;rea de cardiologia no Brasil sobre a atualiza&#231;&#227;o de estrat&#233;gias para o tratamento de IAM.</p>
      <sec>
        <title>Uma breve hist&#243;ria do paradigma IAMCSST e IAMSSST</title>
        <p>Infelizmente, e diferentemente de outras doen&#231;as, o IAM tem sido classificado somente de acordo com achados eletrocardiogr&#225;ficos individuais e n&#227;o na sua fisiopatologia. No entanto, o paradigma IAMCSST-IAMSSST, que substituiu a terminologia "infarto do mioc&#225;rdio com onda Q" e "infarto do mioc&#225;rdio sem onda Q" cunhada em 2000, marcou um avan&#231;o significativo na era da terapia com reperfus&#227;o. Ele possibilitou a identifica&#231;&#227;o precoce de pacientes em risco de morte do mioc&#225;rdio antes do desenvolvimento de uma onda Q. Naquela &#233;poca, a tromb&#243;lise era o m&#233;todo de reperfus&#227;o dispon&#237;vel. Uma metan&#225;lise do in&#237;cio da era dessa terapia revelou um N&#250;mero Necess&#225;rio para Tratar (NNT) de 56 para o uso de fibrinol&#237;ticos. Quatro desses estudos, incluindo o estudo ISIS-2, n&#227;o exigiram a presen&#231;a de altera&#231;&#245;es eletrocardiogr&#225;ficas para a inclus&#227;o dos pacientes.<sup><xref ref-type="bibr" rid="B1">1</xref>&#8211;<xref ref-type="bibr" rid="B3">3</xref></sup> Por&#233;m, an&#225;lises de subgrupos encontraram uma associa&#231;&#227;o com a Eleva&#231;&#227;o do segmento ST (EST), mal definida, levando &#224; melhora dos desfechos com trombol&#237;ticos (principalmente estreptoquinase).</p>
        <fig id="f7">
          <graphic xlink:href="1678-4170-abc-121-05-e20230733-30733-gf01.tif"/></fig>
      </sec>
      <sec>
        <title>A falsa dicotomia IAMCSST vs. IAMSSST: evid&#234;ncias crescentes</title>
        <p>O paradigma IAMCSST foi um marco importante na medicina cardiovascular. Contudo, o esfor&#231;o para padronizar os crit&#233;rios IAMCSST exp&#244;s lacunas com consequ&#234;ncias consider&#225;veis para os pacientes.</p>
        <p>Em uma tentativa de reconciliar v&#225;rios crit&#233;rios de EST, Menown et al.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> utilizaram a an&#225;lise de regress&#227;o log&#237;stica em um estudo caso-controle com 190 indiv&#237;duos, para determinar os pontos de corte &#243;timos: &#8805; 2 mm em pelo menos uma deriva&#231;&#227;o anterosseptal (V1&#8211;4) ou &#8805; 1 mm nas demais deriva&#231;&#245;es. Esse estudo usou o CK-MB para confirmar o Infarto do Mioc&#225;rdio (IM) em vez de evid&#234;ncias angiogr&#225;ficas de OCA.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> Essa abordagem metodol&#243;gica impossibilitou a distin&#231;&#227;o entre OCA e NOCA, resultando em uma sensibilidade de somente 56% para o diagn&#243;stico de IAM com base nos biomarcadores.</p>
        <p>Em 2004, Macfarlane et al.,<sup><xref ref-type="bibr" rid="B5">5</xref></sup> em um estudo caso-controle, sugeriram pontos de corte de EST espec&#237;ficos para idade e sexo, aplicando t&#233;cnicas estat&#237;sticas an&#225;logas &#224;s usadas em estudos pr&#233;vios. Contudo, o desfecho prim&#225;rio para a confirma&#231;&#227;o diagn&#243;stica foi novamente baseado nos valores de CK-MB, ignorando-se a confirma&#231;&#227;o diagn&#243;stica de OCA.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Com base nesses estudos caso-controle, a <italic>American Heart Association</italic>, a <italic>American College of Cardiology Foundation</italic>, e a <italic>Heart Rhythm Society</italic> (AHA/ACCF/HRS) redefinem, periodicamente, o que hoje se conhece por "crit&#233;rios IAMST". Essa defini&#231;&#227;o continua a reverberar nas diretrizes posteriores, incluindo a Quarta Defini&#231;&#227;o Universal de IM.<sup><xref ref-type="bibr" rid="B6">6</xref></sup></p>
        <p>Pouco tempo depois que se chegou ao consenso de 2000, d&#250;vidas surgiram acerca da adequa&#231;&#227;o do paradigma IAMCSST-IAMSSST. O r&#243;tulo "IAMCSST", inadvertidamente, enfatizou somente um aspecto de um teste diagn&#243;stico &#8211; a presen&#231;a de EST no eletrocardiograma (ECG).<sup><xref ref-type="bibr" rid="B7">7</xref>&#8211;<xref ref-type="bibr" rid="B9">9</xref></sup> Alguns m&#233;dicos, possivelmente sem saber da origem do paradigma IAMCSST-IAMSSST, podem erroneamente acreditar que pacientes com OCA, mas sem EST no ECG, n&#227;o se beneficiam da terapia de reperfus&#227;o.</p>
        <p>Em 2001, Schmitt et al.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> estavam entres os primeiros que estudaram o paradigma IAMCSST-IAMSSST angiograficamente. Os autores encontraram que 29% dos 418 pacientes com OCA n&#227;o preenchiam os crit&#233;rios de IAMCSST. Particularmente, 50% dos ECGs dos pacientes com oclus&#227;o da art&#233;ria circunflexa n&#227;o preencheram os crit&#233;rios.<sup><xref ref-type="bibr" rid="B10">10</xref></sup></p>
        <p>Em uma an&#225;lise<sup><xref ref-type="bibr" rid="B11">11</xref></sup> post-hoc do ensaio PARAGON-B, 528 (27%) dos 1957 pacientes diagnosticados com S&#237;ndromes Coronarianas Agudas (SCAs) sem EST apresentavam oclus&#227;o total do vaso culpado. Esses pacientes apresentavam maior &#225;rea infartada e maior mortalidade em seis meses ajustada quanto ao risco.</p>
        <p>O estudo TRITON-TIMI-38<sup><xref ref-type="bibr" rid="B12">12</xref></sup> apresentou outra evid&#234;ncia: dos 1198 pacientes com SCAs sem EST e Depress&#245;es do segmento ST (DSTs) isoladas, 314 (26,2%) apresentaram art&#233;rias culpadas completamente oclu&#237;das. Koyama et al.<sup><xref ref-type="bibr" rid="B13">13</xref></sup> tamb&#233;m contribu&#237;ram para esse entendimento, encontrando que, nos casos de IAMSSST, 57% apresentavam fluxo TIMI 0, enquanto entre os pacientes com IAMSSST, 47% apresentavam fluxo TIMI-0, com uma taxa de mortalidade em torno de 5% em ambos os grupos.<sup><xref ref-type="bibr" rid="B13">13</xref></sup> &#201; evidente que IAMSSST com art&#233;rias coron&#225;rias oclu&#237;das s&#227;o essencialmente equivalentes ao IAMSSSTem termos de gravidade e desfechos.</p>
        <p>Em 2021, Meyers et al.<sup><xref ref-type="bibr" rid="B14">14</xref></sup> compararam o paradigma IAMCSST/IAMSSST com o modelo OCA/NOCA. Seu objetivo era identificar diferen&#231;as no tempo de cateterismo e desfechos relacionados entre OCA com IAMCSST e OCA sem IAMCSST. Os autores encontraram que 28% dos pacientes com IAMSSST apresentaram OCA detectada no cateterismo tardio, e 45% dos pacientes com OCA n&#227;o preencheram os crit&#233;rios para IAMCSST. O tamanho da &#225;rea infartada desses pacientes OCA sem IAMCSST foi estatisticamente igual &#224; dos pacientes com OCA e IAMCSST<sup><xref ref-type="bibr" rid="B14">14</xref></sup> Em outro estudo examinaram a acur&#225;cia de marcadores eletrocardiogr&#225;ficos espec&#237;ficos de OCA em compara&#231;&#227;o &#224; dos crit&#233;rios para IAMCSST vigentes. Esses marcadores para OCA pr&#233;-definidos foram bem mais sens&#237;veis e mantinham uma alta especificidade. Tais dados sugerem que uma interpreta&#231;&#227;o precisa do ECG pode identificar rapidamente e de maneira n&#227;o invasiva os pacientes com OCA e sem IAMCSST para reperfus&#227;o imediata.<sup><xref ref-type="bibr" rid="B15">15</xref></sup></p>
        <p>O estudo DIFOCCULT<sup><xref ref-type="bibr" rid="B16">16</xref></sup> de 2020 apresentou evid&#234;ncias ainda mais convincentes. Cardiologistas, usando interpreta&#231;&#227;o de experts do ECG e n&#227;o somente crit&#233;rios de IAMCSST, reclassificaram, de maneira cega, 28% dos pacientes com IAMSSST como OCA; esses pacientes apresentaram mortalidade em longo prazo significativamente maior que pacientes com IAMSSST classificados pelo ECG como apresentando NOCA. Uma metan&#225;lise da acur&#225;cia do teste diagn&#243;stico, conduzido pela nossa equipe, oferece maiores esclarecimentos sobre os desafios diagn&#243;sticos associados com essa condi&#231;&#227;o. N&#243;s encontramos que a sensibilidade agrupada do supradesnivelamento do segmento ST detectar OCA foi somente 43,6% (9IC 95%: 34,7% - 52,9%), sugerindo que mais da metade dos casos de OCA pode n&#227;o apresentar EST. A especificidade foi alta, de 96,5% (IC95%: 91,2%&#8211;98,7%). Outras an&#225;lises empregando a estrat&#233;gia OCA-NOCA demonstraram uma melhor sensibilidade, de 78,1% (IC 95%: 62,7%&#8211;88,3%) e uma especificidade similar de 94,4% (IC95%: 88,6%&#8211;97,3%).<sup><xref ref-type="bibr" rid="B17">17</xref></sup></p>
        <p>Em uma metan&#225;lise de preval&#234;ncia, Khan et al.<sup><xref ref-type="bibr" rid="B18">18</xref></sup> relataram que 25% dos 40 000 pacientes com IAMSSST encontravam-se com oclus&#227;o aguda da art&#233;ria no angiograma realizada no dia seguinte, sem circula&#231;&#227;o colateral. Em compara&#231;&#227;o aos pacientes com IAMSSST e uma art&#233;ria aberta, entre esses indiv&#237;duos, havia uma taxa de mortalidade quase duas vezes maior, mesmo sendo, em m&#233;dia, 15 anos mais jovens e apresentando menos comorbidades.<sup><xref ref-type="bibr" rid="B18">18</xref></sup></p>
        <p>Em outra metan&#225;lise de Hung et al.,<sup><xref ref-type="bibr" rid="B19">19</xref></sup> 34% dos 60 000 pacientes com IAMSSST apresentaram oclus&#227;o total da art&#233;ria coron&#225;ria. Em compara&#231;&#227;o aos pacientes com uma art&#233;ria aberta, os pacientes com OCA apresentaram, ajustados quantos aos outros fatores cl&#237;nicos: fra&#231;&#227;o de eje&#231;&#227;o mais baixa, valores mais altos de biomarcadores, mais choque cardiog&#234;nico, e mortalidade mais alta (OR 1,72, IC95% 1,49-1,98; p &lt; 0,001).<sup><xref ref-type="bibr" rid="B19">19</xref></sup></p>
        <p>O paradigma IAMCSST-IAMSSST, ao definir uma doen&#231;a somente por um aspecto impreciso (EST) de um teste (ECG), negligencia a real fisiopatologia da OCA. Isso resulta no paradoxo do "sem falso negativo": se um paciente tem OCA, sem EST, n&#227;o h&#225; IAMCSST e, portanto, n&#227;o h&#225; teste falso negativo para IAMCSST. Isso resultou na exclus&#227;o de pacientes com OCA sem IAMCSST dos bancos de dados e, assim, em dados padronizados limitados sobre a sensibilidade e a especificidade de a EST em diagnosticar OCA. Essa lacuna na literatura dificulta a tomada de decis&#227;o cl&#237;nica, uma vez que os m&#233;dicos precisam usar crit&#233;rios potencialmente inadequados para abordar a S&#237;ndrome Coronariana Aguda (SCA).</p>
      </sec>
      <sec>
        <title>Urg&#234;ncia no tratamento das art&#233;rias coron&#225;rias oclu&#237;das: "tempo &#233; mioc&#225;rdio"</title>
        <p>Na SCA, a frase "tempo &#233; mioc&#225;rdio" aplica-se aos pacientes com OCA. Para esses, esperar n&#227;o &#233; uma op&#231;&#227;o; a terapia de reperfus&#227;o imediata &#233; imperativa. Os n&#237;veis de troponina, embora comumente usados no diagn&#243;stico de IM, n&#227;o s&#227;o eficazes no diagn&#243;stico de OCA em situa&#231;&#245;es agudas pelas seguintes raz&#245;es;</p>
        <list list-type="bullet">
          <list-item>
            <p>Demora: os resultados de troponina n&#227;o s&#227;o instant&#226;neos; eles demoram tanto para serem adquiridos (coleta de sangue) quanto para serem processados; enquanto isso, o mioc&#225;rdio est&#225; em risco;</p>
          </list-item>
          <list-item>
            <p>Falta de sensibilidade: a troponina ultrassens&#237;vel (us) inicial n&#227;o &#233; sens&#237;vel para OCA; em um estudo, a troponina I-us foi menos sens&#237;vel que o limiar de refer&#234;ncia para IM tipo I (52 ng/L) em 27% dos IAMCSST.<sup><xref ref-type="bibr" rid="B20">20</xref></sup> Em uma segunda popula&#231;&#227;o da vida real, o valor da troponina inicial esteve abaixo que o limite superior de refer&#234;ncia em 47% dos pacientes com IAMCSST.<sup><xref ref-type="bibr" rid="B21">21</xref></sup> Ainda, os n&#237;veis de troponina n&#227;o distinguem les&#227;o mioc&#225;rdica de IAM, IM do tipo 1 do IM do tipo 2, nem OCA de NOCA. Consequentemente, a troponina-us n&#227;o &#233; um marcador confi&#225;vel para a tomada de decis&#227;o cl&#237;nica imediata.</p>
          </list-item>
        </list>
        <p>Talvez a obje&#231;&#227;o mais comum ao fato de que pacientes com OCA e IAMSSST requeiram reperfus&#227;o de emerg&#234;ncia deriva de ensaios randomizados comparando interven&#231;&#245;es imediatas <italic>vs</italic>. tardias em pacientes com IAMSSST e n&#227;o mostrando nenhum benef&#237;cio. No entanto, esses estudos s&#227;o amplamente mal interpretados. Entre esses estudos, o mais not&#225;vel &#233; o estudo TIMACS.<sup><xref ref-type="bibr" rid="B22">22</xref></sup> Nesse estudo, o grupo submetido &#224; "interven&#231;&#227;o precoce" teve um tempo mediano de interven&#231;&#227;o de 16 horas, muito longo para oferecer qualquer benef&#237;cio a pacientes com OCA. Ainda, o TIMACS n&#227;o inclui pacientes sintom&#225;ticos. Contudo, todos os estudos que definiram interven&#231;&#227;o precoce como menos de duas horas e inclu&#237;ram pacientes sintom&#225;ticos demonstraram benef&#237;cio da interven&#231;&#227;o precoce.<sup><xref ref-type="bibr" rid="B22">22</xref>&#8211;<xref ref-type="bibr" rid="B29">29</xref></sup></p>
        <p>Al&#233;m disso, o estudo TIMACS e outros estudos s&#227;o geralmente mal caracterizados por envolver somente pacientes com IAMSSST. No entanto, esse e outros estudos similares tamb&#233;m inclu&#237;ram pacientes sem n&#237;veis elevados de troponina, quem, por defini&#231;&#227;o, apresentavam Angina Inst&#225;vel (AI), e n&#227;o IAM. Sabe-se que n&#237;veis elevados de troponina s&#227;o um forte preditor de um risco elevado de SCA. No caso do TIMACS, 22% dos 3031 pacientes foram diagnosticados com AI, e n&#227;o IAM. Vale notar que os pacientes com troponina negativa, indicativo de AI, nunca pareceram se beneficiar de um tratamento urgente em vez de um tratamento tardio. Como uma reperfus&#227;o mais r&#225;pida poderia levar a um tamanho reduzido da &#225;rea infartada, se n&#227;o h&#225; nenhuma &#225;rea infartada? Consequentemente, a falta de uma diferen&#231;a percept&#237;vel no desfecho prim&#225;rio n&#227;o &#233; surpreendente, uma vez que 22% da popula&#231;&#227;o do estudo n&#227;o apresentaram mecanismo de benef&#237;cio plaus&#237;vel.</p>
        <p>Apesar de um tempo m&#233;dio de espera de 16 horas para cateterismo no grupo da interven&#231;&#227;o "precoce" no TIMACS, observou-se uma tend&#234;ncia not&#225;vel para um benef&#237;cio no desfecho prim&#225;rio, com uma redu&#231;&#227;o de 2,1% no risco absoluto de morte, IM, e acidente vascular cerebral (9,4% vs. 11,5%, RR 0,81, IC95% 0,63-1,04). Isso foi observado apesar do tempo maior de espera para o grupo interven&#231;&#227;o "precoce" e a inclus&#227;o de 22% de pacientes com AI. Ainda, o subgrupo com escore GRACE &gt; 140 mostrou benef&#237;cios em todos os desfechos.</p>
        <p>Um importante ensaio subsequente, frequentemente citado por aqueles que afirmam n&#227;o haver vantagem em rela&#231;&#227;o ao manejo mais precoce do IAMSSST, &#233; o ensaio VERDICT.<sup><xref ref-type="bibr" rid="B29">29</xref></sup> Entre os 2147 pacientes inclu&#237;dos, 80% foram diagnosticados com IAMSSST, e 20% apresentaram AI sem IAM. Novamente, a inclus&#227;o de AI dilui os resultados. Seguindo todas as diretrizes, o estudo excluiu pacientes apresentando dor. No VERDICT, os tempos de angiograma para os grupos precoce e tardio foram 4,7 e 62 horas, respectivamente. Embora 4,7 horas seja uma melhora significativa em compara&#231;&#227;o &#224;s 16 horas no grupo precoce do TIMACS, o tempo continua um atraso consider&#225;vel no tratamento do IM /OCA, um fato prontamente reconhecido no contexto do manejo do IAMSSST. N&#227;o foi surpresa que o desfecho prim&#225;rio, que considerou os potenciais benef&#237;cios de um r&#225;pido angiograma para uma coorte composta tanto por pacientes com IAMSSST assintom&#225;ticos como por pacientes com AI assintom&#225;ticos e troponinas seriadas negativas, n&#227;o produziu uma vantagem percept&#237;vel no grupo precoce.</p>
        <p>No entanto, assim como o ensaio TIMACS,<sup><xref ref-type="bibr" rid="B22">22</xref></sup> no VERDICT,<sup><xref ref-type="bibr" rid="B29">29</xref></sup> o subgrupo com um escore GRACE superior a 140 mostraram benef&#237;cios significativos no desfecho prim&#225;rio. Outras an&#225;lises do grupo de pacientes com IAMSSST revelaram uma redu&#231;&#227;o absoluta de 4% no desfecho prim&#225;rio composto (morte, IAM, e reinterna&#231;&#245;es por isquemia ou insufici&#234;ncia card&#237;aca). Essa diferen&#231;a n&#227;o foi estatisticamente significativa, pois o estudo n&#227;o discerniu uma varia&#231;&#227;o de 4% (28,8% vs. 32,7%, RR 0,85, IC95% 0,71-1,01). Uma interven&#231;&#227;o demonstrando uma redu&#231;&#227;o no risco absoluto de 4% (NNT=25) em um desfecho t&#227;o centralizado no paciente teria uma import&#226;ncia cl&#237;nica se validada por um estudo com poder suficiente. Assim, os resultados do estudo VERDICT n&#227;o contradizem essa proposi&#231;&#227;o.</p>
        <p>Portanto, os estudos mais extensos e pertinentes<sup><xref ref-type="bibr" rid="B22">22</xref>,<xref ref-type="bibr" rid="B29">29</xref></sup> indicam, consistentemente, benef&#237;cios significativos em subgrupos de pacientes com IAMSSST de alto risco. Os estudos tamb&#233;m sugerem que os benef&#237;cios observados no grupo inteiro de pacientes com IAMSSST poderiam ser confirmados se eles tivessem poder suficiente. Esses resultados originam-se de popula&#231;&#245;es em que os pacientes relatavam estar assintom&#225;ticos. Al&#233;m disso, os tempos de interven&#231;&#227;o precoce, 16 horas<sup><xref ref-type="bibr" rid="B22">22</xref></sup> e 4,7 horas<sup><xref ref-type="bibr" rid="B29">29</xref></sup> foram substancialmente mais longos do tempo tipicamente considerado em uma abordagem de emerg&#234;ncia (definido como inferior a 90 minutos). De fato, outro ensaio, o RIDDLE-IAMSST, em que o tempo para Interven&#231;&#227;o Coron&#225;ria Percut&#226;nea (ICP) foi genuinamente mais cedo (1,4 horas), demonstrou que uma estrat&#233;gia invasiva imediata em pacientes com IAMSSST associa-se a taxas mais baixas de morte ou novo IM em compara&#231;&#227;o a uma estrat&#233;gia invasiva tardia.<sup><xref ref-type="bibr" rid="B30">30</xref></sup> Tal discrep&#226;ncia sugere o potencial para mais benef&#237;cios se a interven&#231;&#227;o tivesse sido genuinamente de emerg&#234;ncia, e principalmente se o estudo tivesse sido limitado a pacientes com OCA e IAMSSST com achados espec&#237;ficos no ECG e geralmente sintom&#225;ticos (por exemplo, dor tor&#225;cica persistente). Assim, nossa posi&#231;&#227;o n&#227;o &#233; defender o manejo emergente de todos os casos de IAMSSST principalmente aqueles com sintomas resolvidos. Em vez disso, n&#243;s enfatizamos a import&#226;ncia de reconhecer e tratar prontamente subgrupos de pacientes com IAMSSST e em mais alto risco: os pacientes com OCA. Esses indiv&#237;duos, que sofreram uma oclus&#227;o ou semi oclus&#227;o aguda dos vasos culpados, podem se beneficiar do manejo de emerg&#234;ncia. A maioria pode ser identificada por ECG usando caracter&#237;sticas al&#233;m da EST.</p>
        <p>Diante da cr&#237;tica realidade anat&#244;mica de uma art&#233;ria oclu&#237;da, recomenda-se que o tempo da terapia de reperfus&#227;o para pacientes com OCA seja alinhado com os tempos porta-agulha e porta-bal&#227;o padronizados para os pacientes com IAMCSST. Qualquer demora em se buscar clareza diagn&#243;stica pode levar a danos irrevers&#237;veis no mioc&#225;rdio e um impacto negativo sobre os desfechos.</p>
      </sec>
      <sec>
        <title>O novo paradigma: OCA-NOCA</title>
        <p>Dadas as limita&#231;&#245;es inerentes ao paradigma IAMCSST-IAMSSST, uma abordagem mais cuidadosa foi proposta, focando nos detalhes anat&#244;micos e fisiol&#243;gicos da SCA. Esse paradigma distingue os pacientes em duas categorias:</p>
        <list list-type="bullet">
          <list-item>
            <p>OCA: Essa designa&#231;&#227;o aplica-se a pacientes com OCA ou quase oclus&#227;o, com circula&#231;&#227;o colateral limitada, colocando-os em risco imediato de IAM transmural. Essa condi&#231;&#227;o causa predominantemente IM tipo 1. A necessidade de terapia de reperfus&#227;o para esses pacientes &#233; urgente, independentemente dos achados do ECG. A principal preocupa&#231;&#227;o &#233; a obstru&#231;&#227;o anat&#244;mica e seu risco associado, e n&#227;o os detalhes dos crit&#233;rios eletrocardiogr&#225;ficos. Apesar da import&#226;ncia do ECG, outros achados cl&#237;nicos e diagn&#243;sticos, tais como anormalidades na motilidade da parede no ecocardiograma ou obstru&#231;&#227;o de vaso detectada por angiografia por tomografia computadorizada, pode auxiliar no diagn&#243;stico da OCA, principalmente se o ECG for inconclusivo.</p>
          </list-item>
          <list-item>
            <p>NOCA: Essa categoria inclui pacientes sem oclus&#227;o coron&#225;ria. Por&#233;m, uma vez que a NOCA pode envolver placa rompida inst&#225;vel, os pacientes mant&#234;m-se vulner&#225;veis &#224; potencial trombose e isquemia coron&#225;ria. Eles podem apresentar n&#237;veis elevados de troponina ou altera&#231;&#245;es no ECG, como invers&#227;o da onda T. Embora esses pacientes necessitem de uma angiografia ou de uma interven&#231;&#227;o caso um vaso culpado seja identificado, o ECG n&#227;o &#233; sens&#237;vel para NOCA mas, felizmente, ele n&#227;o precisa ser, pois n&#227;o s&#227;o necess&#225;rias interven&#231;&#245;es imediatas, e o diagn&#243;stico pode aguardar pela medida da troponina.</p>
          </list-item>
        </list>
        <p>Essa classifica&#231;&#227;o busca melhorar nosso entendimento e o manejo da SCA. Ela permite que os m&#233;dicos enfatizem n&#227;o s&#243; o ECG, mas tamb&#233;m a fisiopatologia subjacente, alinhando, de maneira mais pr&#243;xima, os tratamentos &#224;s necessidades individuais do paciente (<xref ref-type="fig" rid="f7">Figura Central</xref>). Meyers e Smith defenderam esse paradigma no seu "Manifesto OMI", que apresenta um direcionamento importante &#224;s pesquisas iminentes e &#224; aplica&#231;&#227;o cl&#237;nica.</p>
        <p>Avan&#231;os na tecnologia t&#234;m influenciado significativamente o refinamento do manejo do IAM. Algoritmos de intelig&#234;ncia artificial mais recentes exibem alta precis&#227;o diagn&#243;stica e est&#227;o em r&#225;pida evolu&#231;&#227;o. Tais avan&#231;os poderiam melhorar o paradigma OCA-NOCA, fornecendo aos m&#233;dicos ferramentas diagn&#243;sticas ainda mais precisas.<sup><xref ref-type="bibr" rid="B31">31</xref>,<xref ref-type="bibr" rid="B32">32</xref></sup></p>
      </sec>
      <sec>
        <title>Outros sinais eletrocardiogr&#225;ficos da OCA</title>
        <p>No cen&#225;rio em evolu&#231;&#227;o do diagn&#243;stico da OCA, um dos sinais eletrocardiogr&#225;ficos chave &#233; a onda T hiperaguda, caracterizada por uma &#225;rea sob a onda T aumentada em rela&#231;&#227;o ao complexo QRS, incluindo uma base larga, comprimento e convexidade aumentadas, e uma tend&#234;ncia &#224; simetria. Visualmente, a onda T parece se expandir em todas as dire&#231;&#245;es &#8211; aproximando-se e se afastando da onda T, e para cima &#8211; resultando em um alargamento do complexo QT e um pico mais arredondado (<xref ref-type="fig" rid="f1">Figura 1</xref>).</p>
        <fig id="f1">
          <label>Figura 1</label>
          <caption>
            <title>Ondas T hiperagudas; eletrocardiograma a 25 mm/s mostrando uma onda T hiperaguda nas deriva&#231;&#245;es V2-V4.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-121-05-e20230733-30733-gf02.tif"/></fig>
        <p>Ondas T invertidas n&#227;o s&#227;o indicativas de fases hiperagudas de infarto, como alguns podem presumir a partir do termo "isquemia subepic&#225;rdica". Ondas T invertidas registradas por deriva&#231;&#245;es sobre o mioc&#225;rdio isqu&#234;mico aparecem ap&#243;s a reperfus&#227;o aguda, e em estados isqu&#234;micos cr&#244;nicos ou subagudos, ou reciprocamente &#224;s ondas T hiperagudas em uma deriva&#231;&#227;o oposta. Quando ondas T negativas est&#227;o presentes, o problema pode n&#227;o estar localizado na zona subepic&#225;rdica das deriva&#231;&#245;es sobrejacentes, e sim em zonas mais distantes, no mioc&#225;rdio oposto.</p>
        <p>Al&#233;m desses sinais, destaca-se o padr&#227;o "De Winter". Estima-se que esse padr&#227;o ocorra em somente 2% dos pacientes com IM anteroapical submetidos &#224; angioplastia prim&#225;ria. No contexto cl&#237;nico de dor tor&#225;cica isqu&#234;mica aguda, o padr&#227;o eletrocardiogr&#225;fico De Winter exibe uma DST medida no ponto J de pelo menos 1 mm nas deriva&#231;&#245;es V1-V2 &#224; V6, seguido por um segmento ST geralmente na ascendente, e uma onda T hiperaguda alta, positiva e sim&#233;trica (<xref ref-type="fig" rid="f2">Figura 2</xref>). Apesar de as ondas T de Winter receberem muita aten&#231;&#227;o, elas n&#227;o s&#227;o mais importantes que a ondas T hiperagudas, das quais correspondem a somente uma pequena fra&#231;&#227;o.</p>
        <fig id="f2">
          <label>Figura 2</label>
          <caption>
            <title>Sinal sutil de De Winter; eletrocardiograma a 25 mm/s mostrando o padr&#227;o de De Winter, caracterizado pela depress&#227;o do segmento ST no ponto J nas deriva&#231;&#245;es V1-V2 a V6, seguida por um ST ascendente e uma curva T positiva, sim&#233;trica, hiperaguda.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-121-05-e20230733-30733-gf03.tif"/></fig>
        <p>Fazendo a transi&#231;&#227;o das ondas T, a distor&#231;&#227;o da por&#231;&#227;o terminal do complexo QRS oferece outra pista diagn&#243;stica. Definida como a aus&#234;ncia de uma onda S abaixo da linha isoel&#233;trica TP e a aus&#234;ncia de uma onda J na deriva&#231;&#227;o V2 ou V3, ela &#233; um achado muito espec&#237;fico da Art&#233;ria Descendente Anterior Esquerda (ADAE) em compara&#231;&#227;o &#224; repolariza&#231;&#227;o precoce.<sup><xref ref-type="bibr" rid="B33">33</xref></sup> Para diferenciar EST isqu&#234;mico do fisiol&#243;gico na V2 e V3, a f&#243;rmula de Smith de quatro vari&#225;veis pode ser usada, com 88,8% de sensibilidade e 94,7% de especificidade (<xref ref-type="fig" rid="f3">Figura 3</xref>).<sup><xref ref-type="bibr" rid="B34">34</xref>,<xref ref-type="bibr" rid="B35">35</xref></sup> A calculadora est&#225; dispon&#237;vel em: Subtle Anterior STEMI Calculator (4-Variable) (mdcalc.com). Outro sinal eletrocardiogr&#225;fico de OCA &#233; o padr&#227;o Aslanger, que est&#225; associado com infarto da parede inferior e Doen&#231;a Arterial Coronariana (DAC) de m&#250;ltiplos vasos, n&#227;o preenchendo os crit&#233;rios cl&#225;ssicos para EST em duas deriva&#231;&#245;es cont&#237;guas. Ele &#233; caracterizado pela EST somente na deriva&#231;&#227;o III. E DST em qualquer das deriva&#231;&#245;es V4-V6, mas n&#227;o em V2, e um segmento ST em V1 maior que em V2.<sup><xref ref-type="bibr" rid="B36">36</xref></sup></p>
        <fig id="f3">
          <label>Figura 3</label>
          <caption>
            <title>Eleva&#231;&#227;o do segmento ST na parede &#226;ntero-apical; eletrocardiograma mostrando uma sutil eleva&#231;&#227;o do segmento ST de aproximadamente 1 mm nas deriva&#231;&#245;es V1-V4, o que n&#227;o preenche o crit&#233;rio estabelecido pela Defini&#231;&#227;o Universal de Infarto do Mioc&#225;rdio; o uso da calculadora de quatro vari&#225;veis indicou oclus&#227;o coronariana aguda (OCA); a angiografia coronariana subsequente confirmou oclus&#227;o da art&#233;ria descendente anterior esquerda.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-121-05-e20230733-30733-gf04.tif"/></fig>
        <p>Outro sinal eletrocardiogr&#225;fico de OCA envolve a oclus&#227;o do ramo diagonal, afetando a parede anteromedial do cora&#231;&#227;o. De acordo com a atual terminologia das paredes do IM, a qual se baseia na resson&#226;ncia magn&#233;tica, as deriva&#231;&#245;es I, aVL e V2 (e ocasionalmente V3) correspondem &#224; parede anteromedial do ventr&#237;culo esquerdo. Em alguns casos, a EST pode ser evidente s&#243; em aVL e V2.<sup><xref ref-type="bibr" rid="B37">37</xref>,<xref ref-type="bibr" rid="B38">38</xref></sup> Essa regi&#227;o &#233; suprida pelo primeiro ramo diagonal da ADAE. Uma falta de conhecimento dessa terminologia poderia levar cardiologistas a pensarem que aVL e V2 n&#227;o s&#227;o deriva&#231;&#245;es cont&#237;guas. Quando essas deriva&#231;&#245;es s&#227;o afetadas, uma mudan&#231;a rec&#237;proca geralmente ocorre na parede inferior, particularmente na deriva&#231;&#227;o III. Esse padr&#227;o espec&#237;fico foi denominado padr&#227;o "bandeira da &#193;frica do Sul".</p>
        <p>O inverso tamb&#233;m parece ser verdadeiro: qualquer depress&#227;o do segmento ST em aVL auxilia no diagn&#243;stico OCA na parede inferior versus pericardite. Um estudo envolvendo 426 pacientes com IM inferior e complexo QRS normal encontrou que 99% das eleva&#231;&#245;es inferiores do segmento ST exibiram algum grau de DST rec&#237;proco na deriva&#231;&#227;o aVL. Isso ocorreu mesmo quando a EST foi sutil (menos que 1mm) e quando havia EST em V5 e em V6. Por outro lado, na pericardite, n&#227;o se observou DST em nenhuma das deriva&#231;&#245;es exceto aVR.<sup><xref ref-type="bibr" rid="B39">39</xref></sup> Outra importante altera&#231;&#227;o a ser considerada &#233; DST nas deriva&#231;&#245;es V1 a V3/V4, que serve como um indicador rec&#237;proco de SE nas deriva&#231;&#245;es V7 a V9, correspondendo &#224; parede lateral do cora&#231;&#227;o.<sup><xref ref-type="bibr" rid="B31">31</xref>,<xref ref-type="bibr" rid="B40">40</xref>,<xref ref-type="bibr" rid="B41">41</xref></sup></p>
        <p>O diagn&#243;stico de IAM torna-se particularmente desafiador quando o paciente apresenta bloqueio de ramo esquerdo (BRE).<sup><xref ref-type="bibr" rid="B42">42</xref></sup> As diretrizes do ACC/AHA de 2013<sup><xref ref-type="bibr" rid="B43">43</xref></sup> e as diretrizes do ESC STEMI de 2017 e 2023<sup><xref ref-type="bibr" rid="B44">44</xref></sup> recomendam que pacientes com suspeita cl&#237;nica de isquemia mioc&#225;rdica e BRE sejam tratados independentemente de o BRE ser previamente conhecido ou n&#227;o. Um fato importante &#233; que as diretrizes enfatizam a presen&#231;a de um BRE novo ou presumidamente novo em si n&#227;o prediz IM.<sup><xref ref-type="bibr" rid="B43">43</xref>&#8211;<xref ref-type="bibr" rid="B45">45</xref></sup> Sgarbossa et al.<sup><xref ref-type="bibr" rid="B46">46</xref></sup> propuseram um sistema de escore que foi posteriormente refinado pela introdu&#231;&#227;o de um crit&#233;rio proporcional, conhecido como crit&#233;rio de Smith modificado, tamb&#233;m validado para ritmo ventricular estimulado.<sup><xref ref-type="bibr" rid="B47">47</xref>,<xref ref-type="bibr" rid="B48">48</xref></sup></p>
        <p>Segundo a Quarta Defini&#231;&#227;o Universal de IM,<sup><xref ref-type="bibr" rid="B6">6</xref></sup> um bloqueio de ramo direito (BRD) novo ou presumidamente novo sem altera&#231;&#245;es no segmento ST ou onda T associadas deve ser considerado como um ECG equivalente &#224; IAMCSST. Essas recomenda&#231;&#245;es s&#227;o primariamente baseadas em um estudo retrospectivo de Widimsky et al.,<sup><xref ref-type="bibr" rid="B49">49</xref></sup> que incluiu 6742 pacientes com IM agudo.<sup><xref ref-type="bibr" rid="B49">49</xref></sup> Nesse estudo, nem todos os pacientes foram submetidos &#224; angiografia de emerg&#234;ncia como um protocolo de ICP prim&#225;ria. Outras evid&#234;ncias desafiam o BRE como um indicador de angiografia coron&#225;ria de emerg&#234;ncia, uma vez que a probabilidade de IM foi similar &#224; de pacientes sem bloqueio.<sup><xref ref-type="bibr" rid="B50">50</xref></sup> Assim, mais dados de desfechos s&#227;o necess&#225;rios para pacientes apresentando dor tor&#225;cica, BRD presumidamente novo, e sem desvio importante de ST.</p>
        <p>Para apresentar uma vis&#227;o sucinta de v&#225;rios sinais e achados discutidos, a <xref ref-type="fig" rid="f4">Figura 4</xref> resume esses elementos para refer&#234;ncia e melhor compreens&#227;o.</p>
        <fig id="f4">
          <label>Figura 4</label>
          <caption>
            <title>Indicadores eletrocardiogr&#225;ficos chave para oclus&#227;o coronariana aguda.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-121-05-e20230733-30733-gf05.tif"/></fig>
      </sec>
      <sec>
        <title>Diretrizes atuais e sua abordagem bin&#225;ria ao diagn&#243;stico de IM agudo</title>
        <p>As diretrizes atuais para o manejo de IAM s&#227;o meticulosamente elaboradas, servindo como base para o tratamento de milhares de pacientes por cardiologistas e cl&#237;nicos gerais. Essas diretrizes afirmam que, se um paciente com OCA, mas sem crit&#233;rios eletrocardiogr&#225;ficos para IAMCSST, chega no departamento de emerg&#234;ncia, &#233; improv&#225;vel que esse paciente seja submetido a cateterismo de urg&#234;ncia dentro do tempo porta-bal&#227;o recomendado para IAMCSST.<sup><xref ref-type="bibr" rid="B51">51</xref></sup> Em vez disso, os m&#233;dicos tipicamente solicitam um teste de troponina, que pode levar de uma a duas horas para ficar pronto. Durante esse intervalo, o paciente geralmente recebe medicamentos antianginosos, inclusive morfina. Embora novos testes de troponina-us forne&#231;am r&#225;pidos resultados,<sup><xref ref-type="bibr" rid="B52">52</xref></sup> um n&#237;vel elevado de troponina confirma um IAM. Se a hist&#243;ria cl&#237;nica seja sugestiva de IM tipo 1, a troponina ainda n&#227;o diferencia OCA de NOCA. Quando o n&#237;vel de troponina aumenta o suficiente para indicar OCA, uma les&#227;o mioc&#225;rdica substancial irrevers&#237;vel j&#225; ocorreu, e a janela cr&#237;tica para o tempo porta-agulha e tempo porta-bal&#227;o j&#225; est&#225; geralmente fechada. Assim, o diagn&#243;stico de OCA deve ser determinado antes de os resultados de troponina estiverem dispon&#237;veis por meio de interpreta&#231;&#227;o do ECG por experts ou uso de intelig&#234;ncia artificial na eletrocardiografia. A morfina pode confundir o diagn&#243;stico ao levar a um falso senso de seguran&#231;a, uma vez que o paciente est&#225; aparentemente sem dor (mas n&#227;o sem isquemia). Portanto, o uso de morfina pode estar associado a um tempo mais longo para realiza&#231;&#227;o da angiografia.<sup><xref ref-type="bibr" rid="B53">53</xref></sup></p>
        <p>As diretrizes brasileiras para IAMSSST recomendam estrat&#233;gias invasivas urgentes para pacientes que apresentam dor tor&#225;cica recorrente ou refrat&#225;ria.<sup><xref ref-type="bibr" rid="B33">33</xref></sup> Essa abordagem serve como uma rede de seguran&#231;a para pacientes com OCA que n&#227;o preenchem crit&#233;rios eletrocardiogr&#225;ficos para IAMCSST. Recomenda-se cateterismo se um paciente apresenta um ECG falso negativo, mas continua com dor tor&#225;cica. Embora essa recomenda&#231;&#227;o seja muito prudente, vale notar que sua implementa&#231;&#227;o n&#227;o &#233; t&#227;o disseminada como pode-se esperar, mesmo em locais em ela &#233; oficialmente endossada.<sup><xref ref-type="bibr" rid="B51">51</xref></sup></p>
        <p>Na OCA, a troponina inicial pode ser positiva ou negativa, similar a alguns casos &#243;bvios de IAMCSST. Geralmente, o cateterismo para IAMSSST &#233; adiado para uma data futura; com sorte, ele pode ocorrer em um momento mais tarde no mesmo dia. No entanto, ambos os cen&#225;rios n&#227;o se alinham aos prazos recomendados pelas diretrizes atuais (<xref ref-type="fig" rid="f5">Figura 5</xref>).</p>
        <fig id="f5">
          <label>Figura 5</label>
          <caption>
            <title>Fluxograma ilustrando a abordagem atual para o diagn&#243;stico de infarto agudo do mioc&#225;rdio; essa tem sido o pilar para o tratamento de muitos pacientes em v&#225;rias &#225;reas m&#233;dicas; o algoritmo retrata as limita&#231;&#245;es de se confiar somente no eletrocardiograma e nos n&#237;veis de troponina.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-121-05-e20230733-30733-gf06.tif"/></fig>
        <p>N&#243;s somos gratos pela aten&#231;&#227;o e pelo rigor aplicados no desenvolvimento dessas diretrizes. No entanto, acreditamos que haja uma oportunidade para uma a&#231;&#227;o mais assertiva nessa &#225;rea. N&#243;s defendemos a introdu&#231;&#227;o de um novo paradigma para a abordagem do IM. Esse paradigma visa ser mais inclusivo e preciso, fornecendo um melhor suporte para cardiologistas, cl&#237;nicos gerais, e estudantes de medicina no futuro.</p>
      </sec>
      <sec>
        <title>Nossa proposta de abordagem para pacientes com dor tor&#225;cica no departamento de emerg&#234;ncia: O paradigma OCA-NOCA</title>
        <p>Considerando a necessidade urgente de um diagn&#243;stico r&#225;pido e preciso de IAM, n&#243;s propusemos uma abordagem refinada que enfatiza a diferencia&#231;&#227;o entre OCA e NOCA. Se um paciente com fatores de risco epidemiol&#243;gicos apresenta-se no departamento de emerg&#234;ncia com angina (ou outros sintomas isqu&#234;micos), o paciente deve ser imediatamente avaliado quanto &#224; potencial OCA (<xref ref-type="fig" rid="f7">Figura Central</xref>). Essa abordagem &#233; delineada para ser tanto pr&#225;tica como efetiva, reconhecendo as complexidades inerentes e as limita&#231;&#245;es no diagn&#243;stico de IAM.</p>
        <p>Processo diagn&#243;stico: passo-a-passo</p>
        <list list-type="order">
          <list-item>
            <p>Avali&#231;&#227;o eletrocardiogr&#225;fica imediata: na chegada no departamento de emerg&#234;ncia, pacientes com fatores de risco epidemiol&#243;gicos e sintomas sugestivos de isquemia (angina ou equivalente) devem ser submetidos a um ECG nos primeiros dez minutos. Essa r&#225;pida avalia&#231;&#227;o &#233; crucial na identifica&#231;&#227;o de potenciais casos de OCA.</p>
          </list-item>
          <list-item>
            <p>Pesquisa por EST no ECG: uma etapa chave na avalia&#231;&#227;o de um paciente com suspeita de IAM no departamento de emerg&#234;ncia &#233; a avalia&#231;&#227;o da EST no ECG. Enquanto a presen&#231;a de uma eleva&#231;&#227;o significativa do ST &#233; um forte indicador de OCA, &#233; crucial compreender que aproximadamente 30-50% dos casos de OCA podem n&#227;o apresentar esse sinal cl&#225;ssico. Isso destaca a import&#226;ncia de n&#227;o se confiar somente na EST no diagn&#243;stico de OCA. Os m&#233;dicos devem estar cientes dessa possibilidade e preparados para maior investiga&#231;&#227;o, mesmo na aus&#234;ncia de eleva&#231;&#227;o importante do segmento ST, para assegurar que os casos de OCA n&#227;o sejam negligenciados.</p>
          </list-item>
          <list-item>
            <p>Procura por outros sinais de OCA: al&#233;m de se avaliar a EST, m&#233;dicos devem estar atentos para identificar outros indicadores eletrocardiogr&#225;ficos que possam sugerir OCA:<sup><xref ref-type="bibr" rid="B54">54</xref>,<xref ref-type="bibr" rid="B55">55</xref></sup> EST sutil (&lt; 1mm) &#233; frequentemente vista na OCA, e qualquer EST &#8805; 1mm na V2-V4 pode ser normal ou por OCA na ADAE; usar a f&#243;rmula de quatro vari&#225;veis para diferenciar;<sup><xref ref-type="bibr" rid="B34">34</xref></sup> ondas T hiperagudas com EST sutil com ou sem EST,<sup><xref ref-type="bibr" rid="B56">56</xref></sup> sinal de De Winter,<sup><xref ref-type="bibr" rid="B57">57</xref>,<xref ref-type="bibr" rid="B58">58</xref></sup> padr&#227;o de Aslanger,<sup><xref ref-type="bibr" rid="B36">36</xref>,<xref ref-type="bibr" rid="B59">59</xref>,<xref ref-type="bibr" rid="B60">60</xref></sup> DST em V1-V4 representando altera&#231;&#245;es rec&#237;procas da parede lateral (V7-V9),<sup><xref ref-type="bibr" rid="B41">41</xref></sup> distor&#231;&#227;o terminal do QRS,<sup><xref ref-type="bibr" rid="B33">33</xref></sup> EST nas deriva&#231;&#245;es inferiores acompanhada por qualquer DST na aVL indicativo de altera&#231;&#245;es rec&#237;procas a partir da parede anterior m&#233;dia,<sup><xref ref-type="bibr" rid="B39">39</xref></sup> crit&#233;rio de Sgarbossa modificado por Smith em casos de BRE<sup><xref ref-type="bibr" rid="B47">47</xref>,<xref ref-type="bibr" rid="B61">61</xref></sup> ou ritmo estimulado.<sup><xref ref-type="bibr" rid="B48">48</xref></sup> A presen&#231;a de qualquer desses sinais necessita reperfus&#227;o imediata. &#201; fundamental reconhecer que uma OCA pode ocorrer mesmo sem esses sinais eletrocardiogr&#225;ficos espec&#237;ficos, ou mesmo com um ECG completamente normal.</p>
          </list-item>
          <list-item>
            <p>ECGs seriados e compara&#231;&#227;o: na aus&#234;ncia de sinais claros de OCA, ECG seriados devem ser realizados, e ECGs pr&#233;vios obtidos para compara&#231;&#227;o. Essa etapa &#233; vital para identificar mudan&#231;as din&#226;micas que possam indicar isquemia mioc&#225;rdica em progresso.</p>
          </list-item>
          <list-item>
            <p>Os pacientes devem receber tratamento com antianginosos. Deve-se evitar o uso de opioides para o al&#237;vio da dor at&#233; o paciente ser encaminhado para o laborat&#243;rio de cateterismo, uma vez que a medica&#231;&#227;o esconder&#225; sintomas isqu&#234;micos. Um paciente com dor tor&#225;cica persistente na SCA requer uma abordagem invasiva urgente, mesmo na aus&#234;ncia de sinais eletrocardiogr&#225;fica na OCA. Paralelamente, &#233; essencial avaliar outras potenciais causas de dor tor&#225;cica que possam n&#227;o responder &#224; terapia antianginosa (<xref ref-type="fig" rid="f6">Figura 6</xref>).</p>
          </list-item>
        </list>
        <fig id="f6">
          <label>Figura 6</label>
          <caption>
            <title>Algoritmo de decis&#227;o proposto para o manejo de dor tor&#225;cica no departamento de emerg&#234;ncia; o fluxograma ilustra uma abordagem abrangente para a avalia&#231;&#227;o e o manejo de pacientes apresentando dor tor&#225;cica no departamento de emerg&#234;ncia. O algoritmo incorpora crit&#233;rios diagn&#243;sticos tradicionais bem como crit&#233;rios detalhados, visando melhorar a identifica&#231;&#227;o e o tratamento de Oclus&#227;o Coronariana Aguda (OCA); etapas chave incluem avalia&#231;&#227;o cl&#237;nica inicial, r&#225;pida avalia&#231;&#227;o por Eletrocardiograma (ECG), e considera&#231;&#227;o tanto de Eleva&#231;&#227;o do Segmento ST (EST) como outros sinais eletrocardiogr&#225;ficos. O algoritmo tamb&#233;m considera a possibilidade de casos falso-negativos de OCA, enfatizando a import&#226;ncia de monitorar dor tor&#225;cica ou altera&#231;&#245;es din&#226;micas no ECG como indicadores de terapia de reperfus&#227;o imediata. Importante notar que, enquanto esse algoritmo proposto oferece um potencial avan&#231;o no manejo de dor tor&#225;cica, sua implementa&#231;&#227;o em uma escala nacional, particularmente no Sistema &#218;nico de Sa&#250;de no Brasil, pode aumentar o n&#250;mero de interven&#231;&#245;es coron&#225;rias percut&#226;neas. Portanto, as implica&#231;&#245;es log&#237;sticas e econ&#244;micas dessa proposta devem ser cuidadosamente consideradas, e posteriormente validadas por ensaios cl&#237;nicos randomizados antes de sua ampla ado&#231;&#227;o; DST: depress&#227;o do segmento ST.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-121-05-e20230733-30733-gf07.tif"/></fig>
        <p>Al&#233;m dos sintomas isqu&#234;micos, ECGs repetidos, e n&#237;veis de troponina, v&#225;rias ferramentas diagn&#243;sticas podem servir como indicadores suplementares para identificar OCA. Tipicamente, a ecocardiografia revela anormalidade na motilidade da parede durante uma OCA; mas, s&#227;o necess&#225;rios contraste &#224; base de microbolhas, t&#233;cnica excelente, e interpreta&#231;&#227;o por profissional experiente para uma alta sensibilidade. Finalmente, uma angiotomografia computadorizada coronariana de emerg&#234;ncia deve ser facilmente acess&#237;vel e an&#225;loga &#224; abordagem atual de se avaliar pacientes com acidente vascular cerebral agudo no contexto de "oclus&#227;o de grandes vasos".<sup><xref ref-type="bibr" rid="B61">61</xref></sup></p>
        <p>Enquanto essa abordagem visa fornecer uma via clara e vi&#225;vel para o diagn&#243;stico de IAM, reconhecemos que nenhum m&#233;todo diagn&#243;stico &#233; infal&#237;vel. A complexidade das apresenta&#231;&#245;es do IAM significa que sempre haver&#225; casos em que o diagn&#243;stico n&#227;o &#233; imediatamente claro. Nossa abordagem &#233; delineada para maximizar a acur&#225;cia diagn&#243;stica e, ao mesmo tempo, ser adapt&#225;vel a nuances de apresenta&#231;&#245;es individuais dos pacientes.</p>
      </sec>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclus&#227;o</title>
      <p>O cen&#225;rio do diagn&#243;stico de IAM est&#225; prestes a sofrer uma mudan&#231;a de paradigma. Enquanto o modelo IAMCSST-IAMSSST nos serviu bem como uma transi&#231;&#227;o da era de reperfus&#227;o, evid&#234;ncias crescentes e observa&#231;&#245;es cl&#237;nicas indicam suas limita&#231;&#245;es em abordar detalhes mais complexos da SCA. Este artigo destaca essas restri&#231;&#245;es e apresenta o paradigma OCA-NOCA como uma estrat&#233;gia mais precisa do ponto de vista anat&#244;mico e fisiol&#243;gico no manejo do IAM. Antecipamos que esta abordagem refinada ir&#225; melhorar os desfechos do paciente otimizando a acur&#225;cia diagn&#243;stica e maximizando a efic&#225;cia das terapias de reperfus&#227;o.</p>
      <p>Apresentamos evid&#234;ncias desafiando a acur&#225;cia diagn&#243;stica e terap&#234;utica do paradigma IAMCSST-IAMSSST, destacando a taxa not&#225;vel de casos negligenciados de infartos do mioc&#225;rdio com oclus&#227;o e das limita&#231;&#245;es em se confiar somente no ECG (e especialmente na EST) e nos n&#237;veis de troponina para tomadas de decis&#245;es cl&#237;nicas. Al&#233;m disso, delineamos a abordagem do Instituto Dante Pazzanese de Cardiologia em diagnosticar pacientes com dor tor&#225;cica no ambiente de emerg&#234;ncia, refor&#231;ando a import&#226;ncia da r&#225;pida avalia&#231;&#227;o do ECG e da terapia de reperfus&#227;o imediata para casos potenciais de OCA.</p>
      <p>N&#243;s acreditamos que o paradigma OCA-NOCA oferece uma dire&#231;&#227;o promissora para pesquisas e pr&#225;tica cl&#237;nica futuras. Ela estimula m&#233;dicos a complementarem testes diagn&#243;sticos convencionais com um maior entendimento da fisiopatologia subjacente da SCA, levando a tratamentos mais ajustados &#224;s necessidades individuais dos pacientes. Acreditamos que este artigo estimular&#225; a discuss&#227;o e a investiga&#231;&#227;o na comunidade de cardiologistas brasileiros, o que aumentar&#225; a precis&#227;o diagn&#243;stica e a efic&#225;cia do tratamento dos pacientes com IAM.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <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 fn-type="other" id="fn2">
        <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" id="fn3">
        <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-group>
    <ref-list>
      <title>Refer&#234;ncias</title>
      <ref id="B1">
        <label>1</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Alpert</surname>
              <given-names>JS</given-names>
            </name>
            <name>
              <surname>Thygesen</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Antman</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Bassand</surname>
              <given-names>JP</given-names>
            </name>
          </person-group>
          <article-title>Myocardial Infarction Redefined--a Consensus Document of The Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2000</year>
          <volume>36</volume>
          <issue>3</issue>
          <fpage>959</fpage>
          <lpage>969</lpage>
          <pub-id pub-id-type="doi">10.1016/s0735-1097(00)00804-4</pub-id>
        </element-citation>
        <mixed-citation>1 Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial Infarction Redefined--a Consensus Document of The Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction. J Am Coll Cardiol. 2000;36(3):959-69. doi: 10.1016/s0735-1097(00)00804-4.</mixed-citation>
      </ref>
      <ref id="B2">
        <label>2</label>
        <element-citation publication-type="journal">
          <article-title>Indications for Fibrinolytic Therapy in Suspected Acute Myocardial Infarction: Collaborative Overview of Early Mortality and Major Morbidity Results from All Randomised Trials of More Than 1000 Patients. Fibrinolytic Therapy Trialists&#8217; (FTT) Collaborative Group</article-title>
          <source>Lancet</source>
          <year>1994</year>
          <volume>343</volume>
          <issue>8893</issue>
          <fpage>311</fpage>
          <lpage>322</lpage>
        </element-citation>
        <mixed-citation>2 Indications for Fibrinolytic Therapy in Suspected Acute Myocardial Infarction: Collaborative Overview of Early Mortality and Major Morbidity Results from All Randomised Trials of More Than 1000 Patients. Fibrinolytic Therapy Trialists&#8217; (FTT) Collaborative Group. Lancet. 1994;343(8893):311-22.</mixed-citation>
      </ref>
      <ref id="B3">
        <label>3</label>
        <element-citation publication-type="journal">
          <article-title>Randomised Trial of Intravenous Streptokinase, Oral Aspirin, Both, or Neither among 17,187 Cases of Suspected Acute Myocardial Infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group</article-title>
          <source>Lancet</source>
          <year>1988</year>
          <volume>2</volume>
          <issue>8607</issue>
          <fpage>349</fpage>
          <lpage>360</lpage>
        </element-citation>
        <mixed-citation>3 Randomised Trial of Intravenous Streptokinase, Oral Aspirin, Both, or Neither among 17,187 Cases of Suspected Acute Myocardial Infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet. 1988;2(8607):349-60.</mixed-citation>
      </ref>
      <ref id="B4">
        <label>4</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Menown</surname>
              <given-names>IB</given-names>
            </name>
            <name>
              <surname>Mackenzie</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Adgey</surname>
              <given-names>AA</given-names>
            </name>
          </person-group>
          <article-title>Optimizing the Initial 12-lead Electrocardiographic Diagnosis of Acute Myocardial Infarction</article-title>
          <source>Eur Heart J</source>
          <year>2000</year>
          <volume>21</volume>
          <issue>4</issue>
          <fpage>275</fpage>
          <lpage>283</lpage>
          <pub-id pub-id-type="doi">10.1053/euhj.1999.1748</pub-id>
        </element-citation>
        <mixed-citation>4 Menown IB, Mackenzie G, Adgey AA. Optimizing the Initial 12-lead Electrocardiographic Diagnosis of Acute Myocardial Infarction. Eur Heart J. 2000;21(4):275-83. doi: 10.1053/euhj.1999.1748.</mixed-citation>
      </ref>
      <ref id="B5">
        <label>5</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Macfarlane</surname>
              <given-names>PW</given-names>
            </name>
            <name>
              <surname>Browne</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Devine</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Clark</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Miller</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Seyal</surname>
              <given-names>J</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Modification of ACC/ESC Criteria for Acute Myocardial Infarction</article-title>
          <source>J Electrocardiol</source>
          <year>2004</year>
          <volume>37</volume>
          <supplement>Suppl</supplement>
          <fpage>98</fpage>
          <lpage>103</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jelectrocard.2004.08.032</pub-id>
        </element-citation>
        <mixed-citation>5 Macfarlane PW, Browne D, Devine B, Clark E, Miller E, Seyal J, et al. Modification of ACC/ESC Criteria for Acute Myocardial Infarction. J Electrocardiol. 2004;37(Suppl):98-103. doi: 10.1016/j.jelectrocard.2004.08.032.</mixed-citation>
      </ref>
      <ref id="B6">
        <label>6</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Thygesen</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Alpert</surname>
              <given-names>JS</given-names>
            </name>
            <name>
              <surname>Jaffe</surname>
              <given-names>AS</given-names>
            </name>
            <name>
              <surname>Chaitman</surname>
              <given-names>BR</given-names>
            </name>
            <name>
              <surname>Bax</surname>
              <given-names>JJ</given-names>
            </name>
            <name>
              <surname>Morrow</surname>
              <given-names>DA</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Fourth Universal Definition of Myocardial Infarction (2018)</article-title>
          <source>Eur Heart J</source>
          <year>2019</year>
          <volume>40</volume>
          <issue>3</issue>
          <fpage>237</fpage>
          <lpage>269</lpage>
          <pub-id pub-id-type="doi">10.1093/eurheartj/ehy462</pub-id>
        </element-citation>
        <mixed-citation>6 Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth Universal Definition of Myocardial Infarction (2018). Eur Heart J. 2019;40(3):237-69. doi: 10.1093/eurheartj/ehy462.</mixed-citation>
      </ref>
      <ref id="B7">
        <label>7</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Alencar</surname>
              <given-names>JN</given-names>
              <suffix>Neto</suffix>
            </name>
          </person-group>
          <source>Tratado de ECG</source>
          <edition>1st ed.</edition>
          <publisher-loc>Salvador</publisher-loc>
          <publisher-name>Sanar</publisher-name>
          <year>2022</year>
        </element-citation>
        <mixed-citation>7 Alencar Neto JN. Tratado de ECG. 1st ed. Salvador: Sanar; 2022.</mixed-citation>
      </ref>
      <ref id="B8">
        <label>8</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Aslanger</surname>
              <given-names>EK</given-names>
            </name>
            <name>
              <surname>Meyers</surname>
              <given-names>HP</given-names>
            </name>
            <name>
              <surname>Smith</surname>
              <given-names>SW</given-names>
            </name>
          </person-group>
          <article-title>Time for a New Paradigm Shift in Myocardial Infarction</article-title>
          <source>Anatol J Cardiol</source>
          <year>2021</year>
          <volume>25</volume>
          <issue>3</issue>
          <fpage>156</fpage>
          <lpage>162</lpage>
          <pub-id pub-id-type="doi">10.5152/AnatolJCardiol.2021.89304</pub-id>
        </element-citation>
        <mixed-citation>8 Aslanger EK, Meyers HP, Smith SW. Time for a New Paradigm Shift in Myocardial Infarction. Anatol J Cardiol. 2021;25(3):156-62. doi: 10.5152/AnatolJCardiol.2021.89304.</mixed-citation>
      </ref>
      <ref id="B9">
        <label>9</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Aslanger</surname>
              <given-names>EK</given-names>
            </name>
            <name>
              <surname>Meyers</surname>
              <given-names>PH</given-names>
            </name>
            <name>
              <surname>Smith</surname>
              <given-names>SW</given-names>
            </name>
          </person-group>
          <article-title>STEMI: A Transitional Fossil in MI Classification?</article-title>
          <source>J Electrocardiol</source>
          <year>2021</year>
          <volume>65</volume>
          <fpage>163</fpage>
          <lpage>169</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jelectrocard.2021.02.001</pub-id>
        </element-citation>
        <mixed-citation>9 Aslanger EK, Meyers PH, Smith SW. STEMI: A Transitional Fossil in MI Classification? J Electrocardiol. 2021;65:163-9. doi: 10.1016/j.jelectrocard.2021.02.001.</mixed-citation>
      </ref>
      <ref id="B10">
        <label>10</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Schmitt</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Lehmann</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Schmieder</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Karch</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Neumann</surname>
              <given-names>FJ</given-names>
            </name>
            <name>
              <surname>Sch&#246;mig</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
          <article-title>Diagnosis of Acute Myocardial Infarction in Angiographically Documented Occluded Infarct Vessel: Limitations of ST-segment Elevation in Standard and Extended ECG Leads</article-title>
          <source>Chest</source>
          <year>2001</year>
          <volume>120</volume>
          <issue>5</issue>
          <fpage>1540</fpage>
          <lpage>1546</lpage>
          <pub-id pub-id-type="doi">10.1378/chest.120.5.1540</pub-id>
        </element-citation>
        <mixed-citation>10 Schmitt C, Lehmann G, Schmieder S, Karch M, Neumann FJ, Sch&#246;mig A. Diagnosis of Acute Myocardial Infarction in Angiographically Documented Occluded Infarct Vessel: Limitations of ST-segment Elevation in Standard and Extended ECG Leads. Chest. 2001;120(5):1540-6. doi: 10.1378/chest.120.5.1540.</mixed-citation>
      </ref>
      <ref id="B11">
        <label>11</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Wang</surname>
              <given-names>TY</given-names>
            </name>
            <name>
              <surname>Zhang</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Fu</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Armstrong</surname>
              <given-names>PW</given-names>
            </name>
            <name>
              <surname>Newby</surname>
              <given-names>LK</given-names>
            </name>
            <name>
              <surname>Gibson</surname>
              <given-names>CM</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Incidence, Distribution, and Prognostic Impact of Occluded Culprit Arteries among Patients with non-ST-elevation Acute Coronary Syndromes Undergoing Diagnostic Angiography</article-title>
          <source>Am Heart J</source>
          <year>2009</year>
          <volume>157</volume>
          <issue>4</issue>
          <fpage>716</fpage>
          <lpage>723</lpage>
          <pub-id pub-id-type="doi">10.1016/j.ahj.2009.01.004</pub-id>
        </element-citation>
        <mixed-citation>11 Wang TY, Zhang M, Fu Y, Armstrong PW, Newby LK, Gibson CM, et al. Incidence, Distribution, and Prognostic Impact of Occluded Culprit Arteries among Patients with non-ST-elevation Acute Coronary Syndromes Undergoing Diagnostic Angiography. Am Heart J. 2009;157(4):716-23. doi: 10.1016/j.ahj.2009.01.004.</mixed-citation>
      </ref>
      <ref id="B12">
        <label>12</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Pride</surname>
              <given-names>YB</given-names>
            </name>
            <name>
              <surname>Tung</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Mohanavelu</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Zorkun</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Wiviott</surname>
              <given-names>SD</given-names>
            </name>
            <name>
              <surname>Antman</surname>
              <given-names>EM</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Angiographic and Clinical Outcomes among Patients with Acute Coronary Syndromes Presenting with Isolated Anterior ST-segment Depression: A TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38) substudy</article-title>
          <source>JACC Cardiovasc Interv</source>
          <year>2010</year>
          <volume>3</volume>
          <issue>8</issue>
          <fpage>806</fpage>
          <lpage>811</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jcin.2010.05.012</pub-id>
        </element-citation>
        <mixed-citation>12 Pride YB, Tung P, Mohanavelu S, Zorkun C, Wiviott SD, Antman EM, et al. Angiographic and Clinical Outcomes among Patients with Acute Coronary Syndromes Presenting with Isolated Anterior ST-segment Depression: A TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38) substudy. JACC Cardiovasc Interv. 2010;3(8):806-11. doi: 10.1016/j.jcin.2010.05.012.</mixed-citation>
      </ref>
      <ref id="B13">
        <label>13</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Koyama</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Hansen</surname>
              <given-names>PS</given-names>
            </name>
            <name>
              <surname>Hanratty</surname>
              <given-names>CG</given-names>
            </name>
            <name>
              <surname>Nelson</surname>
              <given-names>GI</given-names>
            </name>
            <name>
              <surname>Rasmussen</surname>
              <given-names>HH</given-names>
            </name>
          </person-group>
          <article-title>Prevalence of Coronary Occlusion and outcome of an Immediate Invasive Strategy in Suspected Acute Myocardial Infarction with and Without ST-segment Elevation</article-title>
          <source>Am J Cardiol</source>
          <year>2002</year>
          <volume>90</volume>
          <issue>6</issue>
          <fpage>579</fpage>
          <lpage>584</lpage>
          <pub-id pub-id-type="doi">10.1016/s0002-9149(02)02559-6</pub-id>
        </element-citation>
        <mixed-citation>13 Koyama Y, Hansen PS, Hanratty CG, Nelson GI, Rasmussen HH. Prevalence of Coronary Occlusion and outcome of an Immediate Invasive Strategy in Suspected Acute Myocardial Infarction with and Without ST-segment Elevation. Am J Cardiol. 2002;90(6):579-84. doi: 10.1016/s0002-9149(02)02559-6.</mixed-citation>
      </ref>
      <ref id="B14">
        <label>14</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Meyers</surname>
              <given-names>HP</given-names>
            </name>
            <name>
              <surname>Bracey</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Lee</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Lichtenheld</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Li</surname>
              <given-names>WJ</given-names>
            </name>
            <name>
              <surname>Singer</surname>
              <given-names>DD</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Comparison of the ST-Elevation Myocardial Infarction (STEMI) vs. NSTEMI and Occlusion MI (OMI) vs. NOMI Paradigms of Acute MI</article-title>
          <source>J Emerg Med</source>
          <year>2021</year>
          <volume>60</volume>
          <issue>3</issue>
          <fpage>273</fpage>
          <lpage>284</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jemermed.2020.10.026</pub-id>
        </element-citation>
        <mixed-citation>14 Meyers HP, Bracey A, Lee D, Lichtenheld A, Li WJ, Singer DD, et al. Comparison of the ST-Elevation Myocardial Infarction (STEMI) vs. NSTEMI and Occlusion MI (OMI) vs. NOMI Paradigms of Acute MI. J Emerg Med. 2021;60(3):273-84. doi: 10.1016/j.jemermed.2020.10.026.</mixed-citation>
      </ref>
      <ref id="B15">
        <label>15</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Meyers</surname>
              <given-names>HP</given-names>
            </name>
            <name>
              <surname>Bracey</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Lee</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Lichtenheld</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Li</surname>
              <given-names>WJ</given-names>
            </name>
            <name>
              <surname>Singer</surname>
              <given-names>DD</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Accuracy of OMI ECG Findings Versus STEMI Criteria for Diagnosis of Acute Coronary Occlusion Myocardial Infarction</article-title>
          <source>Int J Cardiol Heart Vasc</source>
          <year>2021</year>
          <volume>33</volume>
          <fpage>100767</fpage>
          <lpage>100767</lpage>
          <pub-id pub-id-type="doi">10.1016/j.ijcha.2021.100767</pub-id>
        </element-citation>
        <mixed-citation>15 Meyers HP, Bracey A, Lee D, Lichtenheld A, Li WJ, Singer DD, et al. Accuracy of OMI ECG Findings Versus STEMI Criteria for Diagnosis of Acute Coronary Occlusion Myocardial Infarction. Int J Cardiol Heart Vasc. 2021;33:100767. doi: 10.1016/j.ijcha.2021.100767.</mixed-citation>
      </ref>
      <ref id="B16">
        <label>16</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Aslanger</surname>
              <given-names>EK</given-names>
            </name>
            <name>
              <surname>Y&#305;ld&#305;r&#305;mt&#252;rk</surname>
              <given-names>&#214;</given-names>
            </name>
            <name>
              <surname>&#350;im&#351;ek</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Bozbeyo&#287;lu</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>&#350;im&#351;ek</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Y&#252;cel Karabay</surname>
              <given-names>C</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>DIagnostic Accuracy of Electrocardiogram for Acute Coronary OCClUsion Resulting in myocardial Infarction (DIFOCCULT Study)</article-title>
          <source>Int J Cardiol Heart Vasc</source>
          <year>2020</year>
          <volume>30</volume>
          <fpage>100603</fpage>
          <lpage>100603</lpage>
          <pub-id pub-id-type="doi">10.1016/j.ijcha.2020.100603</pub-id>
        </element-citation>
        <mixed-citation>16 Aslanger EK, Y&#305;ld&#305;r&#305;mt&#252;rk &#214;, &#350;im&#351;ek B, Bozbeyo&#287;lu E, &#350;im&#351;ek MA, Y&#252;cel Karabay C, et al. DIagnostic Accuracy of Electrocardiogram for Acute Coronary OCClUsion Resulting in myocardial Infarction (DIFOCCULT Study). Int J Cardiol Heart Vasc. 2020;30:100603. doi: 10.1016/j.ijcha.2020.100603.</mixed-citation>
      </ref>
      <ref id="B17">
        <label>17</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Neto</surname>
              <given-names>JNA</given-names>
            </name>
            <name>
              <surname>Scheffer</surname>
              <given-names>MK</given-names>
            </name>
            <name>
              <surname>Correia</surname>
              <given-names>BP</given-names>
            </name>
            <name>
              <surname>Franchini</surname>
              <given-names>KG</given-names>
            </name>
            <name>
              <surname>Felicioni</surname>
              <given-names>SP</given-names>
            </name>
            <name>
              <surname>De Marchi</surname>
              <given-names>MFN</given-names>
            </name>
          </person-group>
          <article-title>Systematic Review and Meta-analysis of Diagnostic Test Accuracy of ST-segment Elevation for Acute Coronary Occlusion</article-title>
          <source>Int J Cardiol</source>
          <year>2024</year>
          <volume>402</volume>
          <fpage>131889</fpage>
          <lpage>131889</lpage>
          <pub-id pub-id-type="doi">10.1016/j.ijcard.2024.131889</pub-id>
        </element-citation>
        <mixed-citation>17 Neto JNA, Scheffer MK, Correia BP, Franchini KG, Felicioni SP, De Marchi MFN. Systematic Review and Meta-analysis of Diagnostic Test Accuracy of ST-segment Elevation for Acute Coronary Occlusion. Int J Cardiol. 2024;402:131889. doi: 10.1016/j.ijcard.2024.131889.</mixed-citation>
      </ref>
      <ref id="B18">
        <label>18</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Khan</surname>
              <given-names>AR</given-names>
            </name>
            <name>
              <surname>Golwala</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Tripathi</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Bin Abdulhak</surname>
              <given-names>AA</given-names>
            </name>
            <name>
              <surname>Bavishi</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Riaz</surname>
              <given-names>H</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Impact of Total Occlusion of Culprit Artery in Acute Non-ST Elevation Myocardial Infarction: A Systematic Review and Meta-analysis</article-title>
          <source>Eur Heart J</source>
          <year>2017</year>
          <volume>38</volume>
          <issue>41</issue>
          <fpage>3082</fpage>
          <lpage>3089</lpage>
          <pub-id pub-id-type="doi">10.1093/eurheartj/ehx418</pub-id>
        </element-citation>
        <mixed-citation>18 Khan AR, Golwala H, Tripathi A, Bin Abdulhak AA, Bavishi C, Riaz H, et al. Impact of Total Occlusion of Culprit Artery in Acute Non-ST Elevation Myocardial Infarction: A Systematic Review and Meta-analysis. Eur Heart J. 2017;38(41):3082-9. doi: 10.1093/eurheartj/ehx418.</mixed-citation>
      </ref>
      <ref id="B19">
        <label>19</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Hung</surname>
              <given-names>CS</given-names>
            </name>
            <name>
              <surname>Chen</surname>
              <given-names>YH</given-names>
            </name>
            <name>
              <surname>Huang</surname>
              <given-names>CC</given-names>
            </name>
            <name>
              <surname>Lin</surname>
              <given-names>MS</given-names>
            </name>
            <name>
              <surname>Yeh</surname>
              <given-names>CF</given-names>
            </name>
            <name>
              <surname>Li</surname>
              <given-names>HY</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Prevalence and Outcome of Patients with non-ST Segment Elevation Myocardial Infarction with Occluded "Culprit" Artery - A Systemic Review and Meta-analysis</article-title>
          <source>Crit Care</source>
          <year>2018</year>
          <volume>22</volume>
          <issue>1</issue>
          <fpage>34</fpage>
          <lpage>34</lpage>
          <pub-id pub-id-type="doi">10.1186/s13054-018-1944-x</pub-id>
        </element-citation>
        <mixed-citation>19 Hung CS, Chen YH, Huang CC, Lin MS, Yeh CF, Li HY, et al. Prevalence and Outcome of Patients with non-ST Segment Elevation Myocardial Infarction with Occluded "Culprit" Artery - A Systemic Review and Meta-analysis. Crit Care. 2018;22(1):34. doi: 10.1186/s13054-018-1944-x.</mixed-citation>
      </ref>
      <ref id="B20">
        <label>20</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Wereski</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Chapman</surname>
              <given-names>AR</given-names>
            </name>
            <name>
              <surname>Lee</surname>
              <given-names>KK</given-names>
            </name>
            <name>
              <surname>Smith</surname>
              <given-names>SW</given-names>
            </name>
            <name>
              <surname>Lowe</surname>
              <given-names>DJ</given-names>
            </name>
            <name>
              <surname>Gray</surname>
              <given-names>A</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>High-Sensitivity Cardiac Troponin Concentrations at Presentation in Patients With ST-Segment Elevation Myocardial Infarction</article-title>
          <source>JAMA Cardiol</source>
          <year>2020</year>
          <volume>5</volume>
          <issue>11</issue>
          <fpage>1302</fpage>
          <lpage>1304</lpage>
          <pub-id pub-id-type="doi">10.1001/jamacardio.2020.2867</pub-id>
        </element-citation>
        <mixed-citation>20 Wereski R, Chapman AR, Lee KK, Smith SW, Lowe DJ, Gray A, et al. High-Sensitivity Cardiac Troponin Concentrations at Presentation in Patients With ST-Segment Elevation Myocardial Infarction. JAMA Cardiol. 2020;5(11):1302-4. doi: 10.1001/jamacardio.2020.2867.</mixed-citation>
      </ref>
      <ref id="B21">
        <label>21</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Wanamaker</surname>
              <given-names>BL</given-names>
            </name>
            <name>
              <surname>Seth</surname>
              <given-names>MM</given-names>
            </name>
            <name>
              <surname>Sukul</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Dixon</surname>
              <given-names>SR</given-names>
            </name>
            <name>
              <surname>Bhatt</surname>
              <given-names>DL</given-names>
            </name>
            <name>
              <surname>Madder</surname>
              <given-names>RD</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Relationship Between Troponin on Presentation and In-Hospital Mortality in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention</article-title>
          <source>J Am Heart Assoc</source>
          <year>2019</year>
          <volume>8</volume>
          <issue>19</issue>
          <elocation-id>e013551</elocation-id>
          <pub-id pub-id-type="doi">10.1161/JAHA.119.013551</pub-id>
        </element-citation>
        <mixed-citation>21 Wanamaker BL, Seth MM, Sukul D, Dixon SR, Bhatt DL, Madder RD, et al. Relationship Between Troponin on Presentation and In-Hospital Mortality in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention. J Am Heart Assoc. 2019;8(19):e013551. doi: 10.1161/JAHA.119.013551.</mixed-citation>
      </ref>
      <ref id="B22">
        <label>22</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Mehta</surname>
              <given-names>SR</given-names>
            </name>
            <name>
              <surname>Granger</surname>
              <given-names>CB</given-names>
            </name>
            <name>
              <surname>Boden</surname>
              <given-names>WE</given-names>
            </name>
            <name>
              <surname>Steg</surname>
              <given-names>PG</given-names>
            </name>
            <name>
              <surname>Bassand</surname>
              <given-names>JP</given-names>
            </name>
            <name>
              <surname>Faxon</surname>
              <given-names>DP</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Early Versus Delayed Invasive Intervention in Acute Coronary Syndromes</article-title>
          <source>N Engl J Med</source>
          <year>2009</year>
          <volume>360</volume>
          <issue>21</issue>
          <fpage>2165</fpage>
          <lpage>2175</lpage>
          <pub-id pub-id-type="doi">10.1056/NEJMoa0807986</pub-id>
        </element-citation>
        <mixed-citation>22 Mehta SR, Granger CB, Boden WE, Steg PG, Bassand JP, Faxon DP, et al. Early Versus Delayed Invasive Intervention in Acute Coronary Syndromes. N Engl J Med. 2009;360(21):2165-75. doi: 10.1056/NEJMoa0807986.</mixed-citation>
      </ref>
      <ref id="B23">
        <label>23</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Montalescot</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Cayla</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Collet</surname>
              <given-names>JP</given-names>
            </name>
            <name>
              <surname>Elhadad</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Beygui</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Le Breton</surname>
              <given-names>H</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Immediate vs Delayed Intervention for Acute Coronary Syndromes: A Randomized Clinical Trial</article-title>
          <source>JAMA</source>
          <year>2009</year>
          <volume>302</volume>
          <issue>9</issue>
          <fpage>947</fpage>
          <lpage>954</lpage>
          <pub-id pub-id-type="doi">10.1001/jama.2009.1267</pub-id>
        </element-citation>
        <mixed-citation>23 Montalescot G, Cayla G, Collet JP, Elhadad S, Beygui F, Le Breton H, et al. Immediate vs Delayed Intervention for Acute Coronary Syndromes: A Randomized Clinical Trial. JAMA. 2009;302(9):947-54. doi: 10.1001/jama.2009.1267.</mixed-citation>
      </ref>
      <ref id="B24">
        <label>24</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Neumann</surname>
              <given-names>FJ</given-names>
            </name>
            <name>
              <surname>Kastrati</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Pogatsa-Murray</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Mehilli</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Bollwein</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Bestehorn</surname>
              <given-names>HP</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Evaluation of Prolonged Antithrombotic Pretreatment ("Cooling-off" Strategy) Before Intervention in Patients with Unstable Coronary Syndromes: A Randomized Controlled Trial</article-title>
          <source>JAMA</source>
          <year>2003</year>
          <volume>290</volume>
          <issue>12</issue>
          <fpage>1593</fpage>
          <lpage>1599</lpage>
          <pub-id pub-id-type="doi">10.1001/jama.290.12.1593</pub-id>
        </element-citation>
        <mixed-citation>24 Neumann FJ, Kastrati A, Pogatsa-Murray G, Mehilli J, Bollwein H, Bestehorn HP, et al. Evaluation of Prolonged Antithrombotic Pretreatment ("Cooling-off" Strategy) Before Intervention in Patients with Unstable Coronary Syndromes: A Randomized Controlled Trial. JAMA. 2003;290(12):1593-9. doi: 10.1001/jama.290.12.1593.</mixed-citation>
      </ref>
      <ref id="B25">
        <label>25</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>van &#8216;t Hof</surname>
              <given-names>AW</given-names>
            </name>
            <name>
              <surname>de Vries</surname>
              <given-names>ST</given-names>
            </name>
            <name>
              <surname>Dambrink</surname>
              <given-names>JH</given-names>
            </name>
            <name>
              <surname>Miedema</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Suryapranata</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Hoorntje</surname>
              <given-names>JC</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>A Comparison of Two Invasive Strategies in Patients with Non-ST Elevation Acute Coronary Syndromes: Results of the Early or Late Intervention in unStable Angina (ELISA) Pilot Study. 2b/3a Upstream Therapy and Acute Coronary Syndromes</article-title>
          <source>Eur Heart J</source>
          <year>2003</year>
          <volume>24</volume>
          <issue>15</issue>
          <fpage>1401</fpage>
          <lpage>1405</lpage>
          <pub-id pub-id-type="doi">10.1016/s0195-668x(03)00259-8</pub-id>
        </element-citation>
        <mixed-citation>25 van &#8216;t Hof AW, de Vries ST, Dambrink JH, Miedema K, Suryapranata H, Hoorntje JC, et al. A Comparison of Two Invasive Strategies in Patients with Non-ST Elevation Acute Coronary Syndromes: Results of the Early or Late Intervention in unStable Angina (ELISA) Pilot Study. 2b/3a Upstream Therapy and Acute Coronary Syndromes. Eur Heart J. 2003;24(15):1401-5. doi: 10.1016/s0195-668x(03)00259-8.</mixed-citation>
      </ref>
      <ref id="B26">
        <label>26</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Thiele</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Rach</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Klein</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Pfeiffer</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Hartmann</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Hambrecht</surname>
              <given-names>R</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Optimal Timing of Invasive Angiography in Stable Non-ST-elevation Myocardial Infarction: The Leipzig Immediate Versus Early and Late Percutaneous Coronary Intervention Trial in NSTEMI (LIPSIA-NSTEMI Trial)</article-title>
          <source>Eur Heart J</source>
          <year>2012</year>
          <volume>33</volume>
          <issue>16</issue>
          <fpage>2035</fpage>
          <lpage>2043</lpage>
          <pub-id pub-id-type="doi">10.1093/eurheartj/ehr418</pub-id>
        </element-citation>
        <mixed-citation>26 Thiele H, Rach J, Klein N, Pfeiffer D, Hartmann A, Hambrecht R, et al. Optimal Timing of Invasive Angiography in Stable Non-ST-elevation Myocardial Infarction: The Leipzig Immediate Versus Early and Late Percutaneous Coronary Intervention Trial in NSTEMI (LIPSIA-NSTEMI Trial). Eur Heart J. 2012;33(16):2035-43. doi: 10.1093/eurheartj/ehr418.</mixed-citation>
      </ref>
      <ref id="B27">
        <label>27</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Reuter</surname>
              <given-names>PG</given-names>
            </name>
            <name>
              <surname>Rouchy</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Cattan</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Benamer</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Jullien</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Beruben</surname>
              <given-names>A</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Early Invasive Strategy in High-risk Acute Coronary Syndrome Without ST-segment Elevation. The Sisca Randomized Trial</article-title>
          <source>Int J Cardiol</source>
          <year>2015</year>
          <volume>182</volume>
          <fpage>414</fpage>
          <lpage>418</lpage>
          <pub-id pub-id-type="doi">10.1016/j.ijcard.2014.12.089</pub-id>
        </element-citation>
        <mixed-citation>27 Reuter PG, Rouchy C, Cattan S, Benamer H, Jullien T, Beruben A, et al. Early Invasive Strategy in High-risk Acute Coronary Syndrome Without ST-segment Elevation. The Sisca Randomized Trial. Int J Cardiol. 2015;182:414-8. doi: 10.1016/j.ijcard.2014.12.089.</mixed-citation>
      </ref>
      <ref id="B28">
        <label>28</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Katritsis</surname>
              <given-names>DG</given-names>
            </name>
            <name>
              <surname>Siontis</surname>
              <given-names>GC</given-names>
            </name>
            <name>
              <surname>Kastrati</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>van't Hof</surname>
              <given-names>AW</given-names>
            </name>
            <name>
              <surname>Neumann</surname>
              <given-names>FJ</given-names>
            </name>
            <name>
              <surname>Siontis</surname>
              <given-names>KC</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Optimal Timing of Coronary Angiography and Potential Intervention in Non-ST-elevation Acute Coronary Syndromes</article-title>
          <source>Eur Heart J</source>
          <year>2011</year>
          <volume>32</volume>
          <issue>1</issue>
          <fpage>32</fpage>
          <lpage>40</lpage>
          <pub-id pub-id-type="doi">10.1093/eurheartj/ehq276</pub-id>
        </element-citation>
        <mixed-citation>28 Katritsis DG, Siontis GC, Kastrati A, van't Hof AW, Neumann FJ, Siontis KC, et al. Optimal Timing of Coronary Angiography and Potential Intervention in Non-ST-elevation Acute Coronary Syndromes. Eur Heart J. 2011;32(1):32-40. doi: 10.1093/eurheartj/ehq276.</mixed-citation>
      </ref>
      <ref id="B29">
        <label>29</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Kofoed</surname>
              <given-names>KF</given-names>
            </name>
            <name>
              <surname>Kelb&#230;k</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Hansen</surname>
              <given-names>PR</given-names>
            </name>
            <name>
              <surname>Torp-Pedersen</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>H&#248;fsten</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Kl&#248;vgaard</surname>
              <given-names>L</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Early Versus Standard Care Invasive Examination and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome</article-title>
          <source>Circulation</source>
          <year>2018</year>
          <volume>138</volume>
          <issue>24</issue>
          <fpage>2741</fpage>
          <lpage>2750</lpage>
          <pub-id pub-id-type="doi">10.1161/CIRCULATIONAHA.118.037152</pub-id>
        </element-citation>
        <mixed-citation>29 Kofoed KF, Kelb&#230;k H, Hansen PR, Torp-Pedersen C, H&#248;fsten D, Kl&#248;vgaard L, et al. Early Versus Standard Care Invasive Examination and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome. Circulation. 2018;138(24):2741-50. doi: 10.1161/CIRCULATIONAHA.118.037152.</mixed-citation>
      </ref>
      <ref id="B30">
        <label>30</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Milosevic</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Vasiljevic-Pokrajcic</surname>
              <given-names>Z</given-names>
            </name>
            <name>
              <surname>Milasinovic</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Marinkovic</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Vukcevic</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Stefanovic</surname>
              <given-names>B</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Immediate Versus Delayed Invasive Intervention for Non-STEMI Patients: The RIDDLE-NSTEMI Study</article-title>
          <source>JACC Cardiovasc Interv</source>
          <year>2016</year>
          <volume>9</volume>
          <issue>6</issue>
          <fpage>541</fpage>
          <lpage>549</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jcin.2015.11.018</pub-id>
        </element-citation>
        <mixed-citation>30 Milosevic A, Vasiljevic-Pokrajcic Z, Milasinovic D, Marinkovic J, Vukcevic V, Stefanovic B, et al. Immediate Versus Delayed Invasive Intervention for Non-STEMI Patients: The RIDDLE-NSTEMI Study. JACC Cardiovasc Interv. 2016;9(6):541-9. doi: 10.1016/j.jcin.2015.11.018.</mixed-citation>
      </ref>
      <ref id="B31">
        <label>31</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Al-Zaiti</surname>
              <given-names>SS</given-names>
            </name>
            <name>
              <surname>Martin-Gill</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Z&#232;gre-Hemsey</surname>
              <given-names>JK</given-names>
            </name>
            <name>
              <surname>Bouzid</surname>
              <given-names>Z</given-names>
            </name>
            <name>
              <surname>Faramand</surname>
              <given-names>Z</given-names>
            </name>
            <name>
              <surname>Alrawashdeh</surname>
              <given-names>MO</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Machine Learning for ECG Diagnosis and Risk Stratification of Occlusion Myocardial Infarction</article-title>
          <source>Nat Med</source>
          <year>2023</year>
          <volume>29</volume>
          <issue>7</issue>
          <fpage>1804</fpage>
          <lpage>1813</lpage>
          <pub-id pub-id-type="doi">10.1038/s41591-023-02396-3</pub-id>
        </element-citation>
        <mixed-citation>31 Al-Zaiti SS, Martin-Gill C, Z&#232;gre-Hemsey JK, Bouzid Z, Faramand Z, Alrawashdeh MO, et al. Machine Learning for ECG Diagnosis and Risk Stratification of Occlusion Myocardial Infarction. Nat Med. 2023;29(7):1804-13. doi: 10.1038/s41591-023-02396-3.</mixed-citation>
      </ref>
      <ref id="B32">
        <label>32</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Herman</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Meyers</surname>
              <given-names>HP</given-names>
            </name>
            <name>
              <surname>Smith</surname>
              <given-names>SW</given-names>
            </name>
            <name>
              <surname>Bertolone</surname>
              <given-names>DT</given-names>
            </name>
            <name>
              <surname>Leone</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Bermpeis</surname>
              <given-names>K</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>International Evaluation of An Artificial Intelligence-powered Electrocardiogram Model Detecting Acute Coronary Occlusion Myocardial Infarction</article-title>
          <source>Eur Heart J Digit Health</source>
          <year>2023</year>
          <volume>5</volume>
          <issue>2</issue>
          <fpage>123</fpage>
          <lpage>133</lpage>
          <pub-id pub-id-type="doi">10.1093/ehjdh/ztad074</pub-id>
        </element-citation>
        <mixed-citation>32 Herman R, Meyers HP, Smith SW, Bertolone DT, Leone A, Bermpeis K, et al. International Evaluation of An Artificial Intelligence-powered Electrocardiogram Model Detecting Acute Coronary Occlusion Myocardial Infarction. Eur Heart J Digit Health. 2023;5(2):123-33. doi: 10.1093/ehjdh/ztad074.</mixed-citation>
      </ref>
      <ref id="B33">
        <label>33</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Lee</surname>
              <given-names>DH</given-names>
            </name>
            <name>
              <surname>Walsh</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Smith</surname>
              <given-names>SW</given-names>
            </name>
          </person-group>
          <article-title>Terminal QRS Distortion is Present in Anterior Myocardial Infarction but Absent in Early Repolarization</article-title>
          <source>Am J Emerg Med</source>
          <year>2016</year>
          <volume>34</volume>
          <issue>11</issue>
          <fpage>2182</fpage>
          <lpage>2185</lpage>
          <pub-id pub-id-type="doi">10.1016/j.ajem.2016.08.053</pub-id>
        </element-citation>
        <mixed-citation>33 Lee DH, Walsh B, Smith SW. Terminal QRS Distortion is Present in Anterior Myocardial Infarction but Absent in Early Repolarization. Am J Emerg Med. 2016;34(11):2182-5. doi: 10.1016/j.ajem.2016.08.053.</mixed-citation>
      </ref>
      <ref id="B34">
        <label>34</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Driver</surname>
              <given-names>BE</given-names>
            </name>
            <name>
              <surname>Khalil</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Henry</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Kazmi</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Adil</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Smith</surname>
              <given-names>SW</given-names>
            </name>
          </person-group>
          <article-title>A New 4-variable Formula to Differentiate Normal Variant ST Segment Elevation in V2-V4 (Early Repolarization) from Subtle Left Anterior Descending Coronary Occlusion - Adding QRS Amplitude of V2 Improves the Model</article-title>
          <source>J Electrocardiol</source>
          <year>2017</year>
          <volume>50</volume>
          <issue>5</issue>
          <fpage>561</fpage>
          <lpage>569</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jelectrocard.2017.04.005</pub-id>
        </element-citation>
        <mixed-citation>34 Driver BE, Khalil A, Henry T, Kazmi F, Adil A, Smith SW. A New 4-variable Formula to Differentiate Normal Variant ST Segment Elevation in V2-V4 (Early Repolarization) from Subtle Left Anterior Descending Coronary Occlusion - Adding QRS Amplitude of V2 Improves the Model. J Electrocardiol. 2017;50(5):561-9. doi: 10.1016/j.jelectrocard.2017.04.005.</mixed-citation>
      </ref>
      <ref id="B35">
        <label>35</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bozbeyo&#287;lu</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Aslanger</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Y&#305;ld&#305;r&#305;mt&#252;rk</surname>
              <given-names>&#214;</given-names>
            </name>
            <name>
              <surname>&#350;im&#351;ek</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Karabay</surname>
              <given-names>CY</given-names>
            </name>
            <name>
              <surname>&#350;im&#351;ek</surname>
              <given-names>MA</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>A Tale of Two Formulas: Differentiation of Subtle Anterior MI from Benign ST Segment Elevation</article-title>
          <source>Ann Noninvasive Electrocardiol</source>
          <year>2018</year>
          <volume>23</volume>
          <issue>6</issue>
          <elocation-id>e12568</elocation-id>
          <pub-id pub-id-type="doi">10.1111/anec.12568</pub-id>
        </element-citation>
        <mixed-citation>35 Bozbeyo&#287;lu E, Aslanger E, Y&#305;ld&#305;r&#305;mt&#252;rk &#214;, &#350;im&#351;ek B, Karabay CY, &#350;im&#351;ek MA, et al. A Tale of Two Formulas: Differentiation of Subtle Anterior MI from Benign ST Segment Elevation. Ann Noninvasive Electrocardiol. 2018;23(6):e12568. doi: 10.1111/anec.12568.</mixed-citation>
      </ref>
      <ref id="B36">
        <label>36</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Aslanger</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Y&#305;ld&#305;r&#305;mt&#252;rk</surname>
              <given-names>&#214;</given-names>
            </name>
            <name>
              <surname>&#350;im&#351;ek</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Sungur</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Cabbar</surname>
              <given-names>AT</given-names>
            </name>
            <name>
              <surname>Bozbeyo&#287;lu</surname>
              <given-names>E</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>A New Electrocardiographic Pattern Indicating Inferior Myocardial Infarction</article-title>
          <source>J Electrocardiol</source>
          <year>2020</year>
          <volume>61</volume>
          <fpage>41</fpage>
          <lpage>46</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jelectrocard.2020.04.008</pub-id>
        </element-citation>
        <mixed-citation>36 Aslanger E, Y&#305;ld&#305;r&#305;mt&#252;rk &#214;, &#350;im&#351;ek B, Sungur A, Cabbar AT, Bozbeyo&#287;lu E, et al. A New Electrocardiographic Pattern Indicating Inferior Myocardial Infarction. J Electrocardiol. 2020;61:41-6. doi: 10.1016/j.jelectrocard.2020.04.008.</mixed-citation>
      </ref>
      <ref id="B37">
        <label>37</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Luna</surname>
              <given-names>AB</given-names>
            </name>
            <name>
              <surname>Cino</surname>
              <given-names>JM</given-names>
            </name>
            <name>
              <surname>Pujadas</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Cygankiewicz</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Carreras</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Garcia-Moll</surname>
              <given-names>X</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Concordance of Electrocardiographic Patterns and Healed Myocardial Infarction Location Detected by Cardiovascular Magnetic Resonance</article-title>
          <source>Am J Cardiol</source>
          <year>2006</year>
          <volume>97</volume>
          <issue>4</issue>
          <fpage>443</fpage>
          <lpage>451</lpage>
          <pub-id pub-id-type="doi">10.1016/j.amjcard.2005.08.068</pub-id>
        </element-citation>
        <mixed-citation>37 Luna AB, Cino JM, Pujadas S, Cygankiewicz I, Carreras F, Garcia-Moll X, et al. Concordance of Electrocardiographic Patterns and Healed Myocardial Infarction Location Detected by Cardiovascular Magnetic Resonance. Am J Cardiol. 2006;97(4):443-51. doi: 10.1016/j.amjcard.2005.08.068.</mixed-citation>
      </ref>
      <ref id="B38">
        <label>38</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Luna</surname>
              <given-names>AB</given-names>
            </name>
          </person-group>
          <article-title>New Heart Wall Terminology and New Electrocardiographic Classification of Q-wave Myocardial Infarction Based on Correlations with Magnetic Resonance Imaging</article-title>
          <source>Rev Esp Cardiol</source>
          <year>2007</year>
          <volume>60</volume>
          <issue>7</issue>
          <fpage>683</fpage>
          <lpage>689</lpage>
        </element-citation>
        <mixed-citation>38 Luna AB. New Heart Wall Terminology and New Electrocardiographic Classification of Q-wave Myocardial Infarction Based on Correlations with Magnetic Resonance Imaging. Rev Esp Cardiol. 2007;60(7):683-9.</mixed-citation>
      </ref>
      <ref id="B39">
        <label>39</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bischof</surname>
              <given-names>JE</given-names>
            </name>
            <name>
              <surname>Worrall</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Thompson</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Marti</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Smith</surname>
              <given-names>SW</given-names>
            </name>
          </person-group>
          <article-title>ST Depression in Lead aVL Differentiates Inferior ST-elevation Myocardial Infarction from Pericarditis</article-title>
          <source>Am J Emerg Med</source>
          <year>2016</year>
          <volume>34</volume>
          <issue>2</issue>
          <fpage>149</fpage>
          <lpage>154</lpage>
          <pub-id pub-id-type="doi">10.1016/j.ajem.2015.09.035</pub-id>
        </element-citation>
        <mixed-citation>39 Bischof JE, Worrall C, Thompson P, Marti D, Smith SW. ST Depression in Lead aVL Differentiates Inferior ST-elevation Myocardial Infarction from Pericarditis. Am J Emerg Med. 2016;34(2):149-54. doi: 10.1016/j.ajem.2015.09.035.</mixed-citation>
      </ref>
      <ref id="B40">
        <label>40</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Nikus</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Pahlm</surname>
              <given-names>O</given-names>
            </name>
            <name>
              <surname>Wagner</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Birnbaum</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Cinca</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Clemmensen</surname>
              <given-names>P</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Electrocardiographic Classification of Acute Coronary Syndromes: A Review by a Committee of the International Society for Holter and Non-Invasive Electrocardiology</article-title>
          <source>J Electrocardiol</source>
          <year>2010</year>
          <volume>43</volume>
          <issue>2</issue>
          <fpage>91</fpage>
          <lpage>103</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jelectrocard.2009.07.009</pub-id>
        </element-citation>
        <mixed-citation>40 Nikus K, Pahlm O, Wagner G, Birnbaum Y, Cinca J, Clemmensen P, et al. Electrocardiographic Classification of Acute Coronary Syndromes: A Review by a Committee of the International Society for Holter and Non-Invasive Electrocardiology. J Electrocardiol. 2010;43(2):91-103. doi: 10.1016/j.jelectrocard.2009.07.009.</mixed-citation>
      </ref>
      <ref id="B41">
        <label>41</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Meyers</surname>
              <given-names>HP</given-names>
            </name>
            <name>
              <surname>Bracey</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Lee</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Lichtenheld</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Li</surname>
              <given-names>WJ</given-names>
            </name>
            <name>
              <surname>Singer</surname>
              <given-names>DD</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Ischemic ST-Segment Depression Maximal in V1-V4 (Versus V5-V6) of Any Amplitude Is Specific for Occlusion Myocardial Infarction (Versus Nonocclusive Ischemia)</article-title>
          <source>J Am Heart Assoc</source>
          <year>2021</year>
          <volume>10</volume>
          <issue>23</issue>
          <elocation-id>e022866</elocation-id>
          <pub-id pub-id-type="doi">10.1161/JAHA.121.022866</pub-id>
        </element-citation>
        <mixed-citation>41 Meyers HP, Bracey A, Lee D, Lichtenheld A, Li WJ, Singer DD, et al. Ischemic ST-Segment Depression Maximal in V1-V4 (Versus V5-V6) of Any Amplitude Is Specific for Occlusion Myocardial Infarction (Versus Nonocclusive Ischemia). J Am Heart Assoc. 2021;10(23):e022866. doi: 10.1161/JAHA.121.022866.</mixed-citation>
      </ref>
      <ref id="B42">
        <label>42</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Nikus</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Birnbaum</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Fiol-Sala</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Rankinen</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Luna</surname>
              <given-names>AB</given-names>
            </name>
          </person-group>
          <article-title>Conduction Disorders in the Setting of Acute STEMI</article-title>
          <source>Curr Cardiol Rev</source>
          <year>2021</year>
          <volume>17</volume>
          <issue>1</issue>
          <fpage>41</fpage>
          <lpage>49</lpage>
          <pub-id pub-id-type="doi">10.2174/1573403X16666200702121937</pub-id>
        </element-citation>
        <mixed-citation>42 Nikus K, Birnbaum Y, Fiol-Sala M, Rankinen J, Luna AB. Conduction Disorders in the Setting of Acute STEMI. Curr Cardiol Rev. 2021;17(1):41-9. doi: 10.2174/1573403X16666200702121937.</mixed-citation>
      </ref>
      <ref id="B43">
        <label>43</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>O'Gara</surname>
              <given-names>PT</given-names>
            </name>
            <name>
              <surname>Kushner</surname>
              <given-names>FG</given-names>
            </name>
            <name>
              <surname>Ascheim</surname>
              <given-names>DD</given-names>
            </name>
            <name>
              <surname>Casey</surname>
              <given-names>DE</given-names>
              <suffix>Jr</suffix>
            </name>
            <name>
              <surname>Chung</surname>
              <given-names>MK</given-names>
            </name>
            <name>
              <surname>Lemos</surname>
              <given-names>JA</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>2013 ACCF/AHA Guideline for the Management of ST-elevation Myocardial Infarction: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines</article-title>
          <source>Circulation</source>
          <year>2013</year>
          <volume>127</volume>
          <issue>4</issue>
          <fpage>362</fpage>
          <lpage>425</lpage>
          <pub-id pub-id-type="doi">10.1161/CIR.0b013e3182742cf6</pub-id>
        </element-citation>
        <mixed-citation>43 O'Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, Lemos JA, et al. 2013 ACCF/AHA Guideline for the Management of ST-elevation Myocardial Infarction: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(4):362-425. doi: 10.1161/CIR.0b013e3182742cf6.</mixed-citation>
      </ref>
      <ref id="B44">
        <label>44</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ibanez</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>James</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Agewall</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Antunes</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Bucciarelli-Ducci</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Bueno</surname>
              <given-names>H</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>2017 ESC Guidelines for the Management of Acute Myocardial Infarction in Patients Presenting with ST-segment Elevation: The Task Force for the Management of Acute Myocardial Infarction in Patients Presenting with ST-segment elevation of the European Society of Cardiology (ESC)</article-title>
          <source>Eur Heart J</source>
          <year>2018</year>
          <volume>39</volume>
          <issue>2</issue>
          <fpage>119</fpage>
          <lpage>177</lpage>
          <pub-id pub-id-type="doi">10.1093/eurheartj/ehx393</pub-id>
        </element-citation>
        <mixed-citation>44 Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. 2017 ESC Guidelines for the Management of Acute Myocardial Infarction in Patients Presenting with ST-segment Elevation: The Task Force for the Management of Acute Myocardial Infarction in Patients Presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39(2):119-77. doi: 10.1093/eurheartj/ehx393.</mixed-citation>
      </ref>
      <ref id="B45">
        <label>45</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Byrne</surname>
              <given-names>RA</given-names>
            </name>
            <name>
              <surname>Rossello</surname>
              <given-names>X</given-names>
            </name>
            <name>
              <surname>Coughlan</surname>
              <given-names>JJ</given-names>
            </name>
            <name>
              <surname>Barbato</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Berry</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Chieffo</surname>
              <given-names>A</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>2023 ESC Guidelines for the Management of Acute Coronary Syndromes</article-title>
          <source>Eur Heart J</source>
          <year>2023</year>
          <volume>44</volume>
          <issue>38</issue>
          <fpage>3720</fpage>
          <lpage>3826</lpage>
          <pub-id pub-id-type="doi">10.1093/eurheartj/ehad191</pub-id>
        </element-citation>
        <mixed-citation>45 Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, et al 2023 ESC Guidelines for the Management of Acute Coronary Syndromes. Eur Heart J. 2023;44(38):3720-826. doi: 10.1093/eurheartj/ehad191.</mixed-citation>
      </ref>
      <ref id="B46">
        <label>46</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Sgarbossa</surname>
              <given-names>EB</given-names>
            </name>
            <name>
              <surname>Pinski</surname>
              <given-names>SL</given-names>
            </name>
            <name>
              <surname>Gates</surname>
              <given-names>KB</given-names>
            </name>
            <name>
              <surname>Wagner</surname>
              <given-names>GS</given-names>
            </name>
          </person-group>
          <article-title>Early Electrocardiographic Diagnosis of Acute Myocardial Infarction in the Presence of Ventricular Paced Rhythm. GUSTO-I Investigators</article-title>
          <source>Am J Cardiol</source>
          <year>1996</year>
          <volume>77</volume>
          <issue>5</issue>
          <fpage>423</fpage>
          <lpage>424</lpage>
          <pub-id pub-id-type="doi">10.1016/s0002-9149(97)89377-0</pub-id>
        </element-citation>
        <mixed-citation>46 Sgarbossa EB, Pinski SL, Gates KB, Wagner GS. Early Electrocardiographic Diagnosis of Acute Myocardial Infarction in the Presence of Ventricular Paced Rhythm. GUSTO-I Investigators. Am J Cardiol. 1996;77(5):423-4. doi: 10.1016/s0002-9149(97)89377-0.</mixed-citation>
      </ref>
      <ref id="B47">
        <label>47</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Smith</surname>
              <given-names>SW</given-names>
            </name>
            <name>
              <surname>Dodd</surname>
              <given-names>KW</given-names>
            </name>
            <name>
              <surname>Henry</surname>
              <given-names>TD</given-names>
            </name>
            <name>
              <surname>Dvorak</surname>
              <given-names>DM</given-names>
            </name>
            <name>
              <surname>Pearce</surname>
              <given-names>LA</given-names>
            </name>
          </person-group>
          <article-title>Diagnosis of ST-Elevation Myocardial Infarction in the Presence of Left Bundle Branch Block with the ST-elevation to S-wave Ratio in a Modified Sgarbossa Rule</article-title>
          <source>Ann Emerg Med</source>
          <year>2012</year>
          <volume>60</volume>
          <issue>6</issue>
          <fpage>766</fpage>
          <lpage>776</lpage>
          <pub-id pub-id-type="doi">10.1016/j.annemergmed.2012.07.119</pub-id>
        </element-citation>
        <mixed-citation>47 Smith SW, Dodd KW, Henry TD, Dvorak DM, Pearce LA. Diagnosis of ST-Elevation Myocardial Infarction in the Presence of Left Bundle Branch Block with the ST-elevation to S-wave Ratio in a Modified Sgarbossa Rule. Ann Emerg Med. 2012;60(6):766-76. doi: 10.1016/j.annemergmed.2012.07.119.</mixed-citation>
      </ref>
      <ref id="B48">
        <label>48</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Dodd</surname>
              <given-names>KW</given-names>
            </name>
            <name>
              <surname>Zvosec</surname>
              <given-names>DL</given-names>
            </name>
            <name>
              <surname>Hart</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Glass</surname>
              <given-names>G</given-names>
              <suffix>3rd</suffix>
            </name>
            <name>
              <surname>Bannister</surname>
              <given-names>LE</given-names>
            </name>
            <name>
              <surname>Body</surname>
              <given-names>RM</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Electrocardiographic Diagnosis of Acute Coronary Occlusion Myocardial Infarction in Ventricular Paced Rhythm Using the Modified Sgarbossa Criteria</article-title>
          <source>Ann Emerg Med</source>
          <year>2021</year>
          <volume>78</volume>
          <issue>4</issue>
          <fpage>517</fpage>
          <lpage>529</lpage>
          <pub-id pub-id-type="doi">10.1016/j.annemergmed.2021.03.036</pub-id>
        </element-citation>
        <mixed-citation>48 Dodd KW, Zvosec DL, Hart MA, Glass G 3rd, Bannister LE, Body RM, et al. Electrocardiographic Diagnosis of Acute Coronary Occlusion Myocardial Infarction in Ventricular Paced Rhythm Using the Modified Sgarbossa Criteria. Ann Emerg Med. 2021;78(4):517-29. doi: 10.1016/j.annemergmed.2021.03.036.</mixed-citation>
      </ref>
      <ref id="B49">
        <label>49</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Widimsky</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Roh&#225;c</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>St&#225;sek</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Kala</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Rokyta</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Kuzmanov</surname>
              <given-names>B</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Early Electrocardiographic Diagnosis of Acute Myocardial Infarction in the Presence of Ventricular Paced Rhythm. GUSTO-I Investigators</article-title>
          <source>Eur Heart J.</source>
          <year>2012</year>
          <volume>33</volume>
          <issue>1</issue>
          <fpage>86</fpage>
          <lpage>95</lpage>
          <pub-id pub-id-type="doi">10.1093/eurheartj/ehr291</pub-id>
        </element-citation>
        <mixed-citation>49 Widimsky P, Roh&#225;c F, St&#225;sek J, Kala P, Rokyta R, Kuzmanov B, et al. Primary Angioplasty in Acute Myocardial Infarction with Right Bundle Branch Block: Should New Onset Right Bundle Branch Block be Added to Future Guidelines as an Indication for Reperfusion Therapy? Eur Heart J. 2012;33(1):86-95. doi: 10.1093/eurheartj/ehr291.</mixed-citation>
      </ref>
      <ref id="B50">
        <label>50</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Neumann</surname>
              <given-names>JT</given-names>
            </name>
            <name>
              <surname>S&#246;rensen</surname>
              <given-names>NA</given-names>
            </name>
            <name>
              <surname>R&#252;bsamen</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Ojeda</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Sch&#228;fer</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Keller</surname>
              <given-names>T</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Right Bundle Branch Block in Patients with Suspected Myocardial Infarction</article-title>
          <source>Eur Heart J Acute Cardiovasc Care</source>
          <year>2019</year>
          <volume>8</volume>
          <issue>2</issue>
          <fpage>161</fpage>
          <lpage>166</lpage>
          <pub-id pub-id-type="doi">10.1177/2048872618809700</pub-id>
        </element-citation>
        <mixed-citation>50 Neumann JT, S&#246;rensen NA, R&#252;bsamen N, Ojeda F, Sch&#228;fer S, Keller T, et al. Right Bundle Branch Block in Patients with Suspected Myocardial Infarction. Eur Heart J Acute Cardiovasc Care. 2019;8(2):161-6. doi: 10.1177/2048872618809700.</mixed-citation>
      </ref>
      <ref id="B51">
        <label>51</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Lupu</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Taha</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Banai</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Shmueli</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Borohovitz</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Matetzky</surname>
              <given-names>S</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Immediate and Early Percutaneous Coronary Intervention in Very High-risk and High-risk Non-ST Segment Elevation Myocardial Infarction Patients</article-title>
          <source>Clin Cardiol</source>
          <year>2022</year>
          <volume>45</volume>
          <issue>4</issue>
          <fpage>359</fpage>
          <lpage>369</lpage>
          <pub-id pub-id-type="doi">10.1002/clc.23781</pub-id>
        </element-citation>
        <mixed-citation>51 Lupu L, Taha L, Banai A, Shmueli H, Borohovitz A, Matetzky S, et al. Immediate and Early Percutaneous Coronary Intervention in Very High-risk and High-risk Non-ST Segment Elevation Myocardial Infarction Patients. Clin Cardiol. 2022;45(4):359-69. doi: 10.1002/clc.23781.</mixed-citation>
      </ref>
      <ref id="B52">
        <label>52</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Apple</surname>
              <given-names>FS</given-names>
            </name>
            <name>
              <surname>Smith</surname>
              <given-names>SW</given-names>
            </name>
            <name>
              <surname>Greenslade</surname>
              <given-names>JH</given-names>
            </name>
            <name>
              <surname>Sandoval</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Parsonage</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>Ranasinghe</surname>
              <given-names>I</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Single High-Sensitivity Point-of-Care Whole-Blood Cardiac Troponin I Measurement to Rule Out Acute Myocardial Infarction at Low Risk</article-title>
          <source>Circulation</source>
          <year>2022</year>
          <volume>146</volume>
          <issue>25</issue>
          <fpage>1918</fpage>
          <lpage>1929</lpage>
          <pub-id pub-id-type="doi">10.1161/CIRCULATIONAHA.122.061148</pub-id>
        </element-citation>
        <mixed-citation>52 Apple FS, Smith SW, Greenslade JH, Sandoval Y, Parsonage W, Ranasinghe I, et al. Single High-Sensitivity Point-of-Care Whole-Blood Cardiac Troponin I Measurement to Rule Out Acute Myocardial Infarction at Low Risk. Circulation. 2022;146(25):1918-29. doi: 10.1161/CIRCULATIONAHA.122.061148.</mixed-citation>
      </ref>
      <ref id="B53">
        <label>53</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bracey</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Meyers</surname>
              <given-names>HP</given-names>
            </name>
            <name>
              <surname>Smith</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Wei</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Singer</surname>
              <given-names>DD</given-names>
            </name>
            <name>
              <surname>Singer</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
          <article-title>Association Between Opioid Analgesia and Delays to Cardiac Catheterization of Patients with Occlusion Myocardial Infarctions</article-title>
          <source>Acad Emerg Med</source>
          <year>020</year>
          <volume>27</volume>
          <supplement>Suppl 1</supplement>
          <fpage>7</fpage>
          <lpage>316</lpage>
        </element-citation>
        <mixed-citation>53 Bracey A, Meyers HP, Smith S, Wei L, Singer DD, Singer A. Association Between Opioid Analgesia and Delays to Cardiac Catheterization of Patients with Occlusion Myocardial Infarctions. Acad Emerg Med. 020;27(Suppl 1):7&#8211;316.</mixed-citation>
      </ref>
      <ref id="B54">
        <label>54</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Miranda</surname>
              <given-names>DF</given-names>
            </name>
            <name>
              <surname>Lobo</surname>
              <given-names>AS</given-names>
            </name>
            <name>
              <surname>Walsh</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Sandoval</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Smith</surname>
              <given-names>SW</given-names>
            </name>
          </person-group>
          <article-title>New Insights Into the Use of the 12-Lead Electrocardiogram for Diagnosing Acute Myocardial Infarction in the Emergency Department</article-title>
          <source>Can J Cardiol</source>
          <year>2018</year>
          <volume>34</volume>
          <issue>2</issue>
          <fpage>132</fpage>
          <lpage>145</lpage>
          <pub-id pub-id-type="doi">10.1016/j.cjca.2017.11.011</pub-id>
        </element-citation>
        <mixed-citation>54 Miranda DF, Lobo AS, Walsh B, Sandoval Y, Smith SW. New Insights Into the Use of the 12-Lead Electrocardiogram for Diagnosing Acute Myocardial Infarction in the Emergency Department. Can J Cardiol. 2018;34(2):132-45. doi: 10.1016/j.cjca.2017.11.011.</mixed-citation>
      </ref>
      <ref id="B55">
        <label>55</label>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <name>
              <surname>Hellerman</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
          <source>OMI Pocket Guide [Internet]</source>
          <publisher-loc>New York</publisher-loc>
          <publisher-name>OMI Pocket</publisher-name>
          <year>2023</year>
          <date-in-citation content-type="access-date">[cited 2023 Sep 9]</date-in-citation>
          <comment>Available from: <ext-link ext-link-type="uri" xlink:href="https://omiguide.org/">https://omiguide.org/</ext-link> </comment>
        </element-citation>
        <mixed-citation>55 Hellerman M. OMI Pocket Guide [Internet]. New York: OMI Pocket; 2023 [cited 2023 Sep 9]. Available from: <ext-link ext-link-type="uri" xlink:href="https://omiguide.org/">https://omiguide.org/</ext-link>.</mixed-citation>
      </ref>
      <ref id="B56">
        <label>56</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Pessah</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Huhtala</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Kosonen</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Eskola</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>P&#233;rez-Riera</surname>
              <given-names>AR</given-names>
            </name>
            <name>
              <surname>Nikus</surname>
              <given-names>K</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Early Ischemic ST-segment and T-wave Changes During Balloon Angioplasty</article-title>
          <source>J Electrocardiol</source>
          <year>2022</year>
          <volume>73</volume>
          <fpage>87</fpage>
          <lpage>95</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jelectrocard.2022.06.003</pub-id>
        </element-citation>
        <mixed-citation>56 Pessah MA, Huhtala H, Kosonen P, Eskola M, P&#233;rez-Riera AR, Nikus K, et al. Early Ischemic ST-segment and T-wave Changes During Balloon Angioplasty. J Electrocardiol. 2022;73:87-95. doi: 10.1016/j.jelectrocard.2022.06.003.</mixed-citation>
      </ref>
      <ref id="B57">
        <label>57</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Winter</surname>
              <given-names>RJ</given-names>
            </name>
            <name>
              <surname>Verouden</surname>
              <given-names>NJ</given-names>
            </name>
            <name>
              <surname>Wellens</surname>
              <given-names>HJ</given-names>
            </name>
            <name>
              <surname>Wilde</surname>
              <given-names>AA</given-names>
            </name>
          </person-group>
          <article-title>A New ECG Sign of Proximal LAD Occlusion</article-title>
          <source>N Engl J Med</source>
          <year>2008</year>
          <volume>359</volume>
          <issue>19</issue>
          <fpage>2071</fpage>
          <lpage>2073</lpage>
          <pub-id pub-id-type="doi">10.1056/NEJMc0804737</pub-id>
        </element-citation>
        <mixed-citation>57 Winter RJ, Verouden NJ, Wellens HJ, Wilde AA. A New ECG Sign of Proximal LAD Occlusion. N Engl J Med. 2008;359(19):2071-3. doi: 10.1056/NEJMc0804737.</mixed-citation>
      </ref>
      <ref id="B58">
        <label>58</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Verouden</surname>
              <given-names>NJ</given-names>
            </name>
            <name>
              <surname>Koch</surname>
              <given-names>KT</given-names>
            </name>
            <name>
              <surname>Peters</surname>
              <given-names>RJ</given-names>
            </name>
            <name>
              <surname>Henriques</surname>
              <given-names>JP</given-names>
            </name>
            <name>
              <surname>Baan</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>van der Schaaf</surname>
              <given-names>RJ</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Persistent Precordial "Hyperacute" T-waves Signify Proximal Left Anterior Descending Artery Occlusion</article-title>
          <source>Heart</source>
          <year>2009</year>
          <volume>95</volume>
          <issue>20</issue>
          <fpage>1701</fpage>
          <lpage>1706</lpage>
          <pub-id pub-id-type="doi">10.1136/hrt.2009.174557</pub-id>
        </element-citation>
        <mixed-citation>58 Verouden NJ, Koch KT, Peters RJ, Henriques JP, Baan J, van der Schaaf RJ, et al. Persistent Precordial "Hyperacute" T-waves Signify Proximal Left Anterior Descending Artery Occlusion. Heart. 2009;95(20):1701-6. doi: 10.1136/hrt.2009.174557.</mixed-citation>
      </ref>
      <ref id="B59">
        <label>59</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Miyauchi</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Kuwazuru</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Arikawa</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Tokutake</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Chaen</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Oketani</surname>
              <given-names>N</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Clinical Features of the Aslanger Pattern to Compensate for the Limitation of ST-Elevation Myocardial Infarction (STEMI) Criteria</article-title>
          <source>Cureus</source>
          <year>2023</year>
          <volume>15</volume>
          <issue>1</issue>
          <elocation-id>e33227</elocation-id>
          <pub-id pub-id-type="doi">10.7759/cureus.33227</pub-id>
        </element-citation>
        <mixed-citation>59 Miyauchi E, Kuwazuru K, Arikawa R, Tokutake D, Chaen H, Oketani N, et al. Clinical Features of the Aslanger Pattern to Compensate for the Limitation of ST-Elevation Myocardial Infarction (STEMI) Criteria. Cureus. 2023;15(1):e33227. doi: 10.7759/cureus.33227.</mixed-citation>
      </ref>
      <ref id="B60">
        <label>60</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Meyers</surname>
              <given-names>HP</given-names>
            </name>
            <name>
              <surname>Limkakeng</surname>
              <given-names>AT</given-names>
              <suffix>Jr</suffix>
            </name>
            <name>
              <surname>Jaffa</surname>
              <given-names>EJ</given-names>
            </name>
            <name>
              <surname>Patel</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Theiling</surname>
              <given-names>BJ</given-names>
            </name>
            <name>
              <surname>Rezaie</surname>
              <given-names>SR</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Validation of the Modified Sgarbossa Criteria for Acute Coronary Occlusion in the Setting of left Bundle Branch Block: A Retrospective Case-control Study</article-title>
          <source>Am Heart J</source>
          <year>2015</year>
          <volume>170</volume>
          <issue>6</issue>
          <fpage>1255</fpage>
          <lpage>1264</lpage>
          <pub-id pub-id-type="doi">10.1016/j.ahj.2015.09.005</pub-id>
        </element-citation>
        <mixed-citation>60 Meyers HP, Limkakeng AT Jr, Jaffa EJ, Patel A, Theiling BJ, Rezaie SR, et al. Validation of the Modified Sgarbossa Criteria for Acute Coronary Occlusion in the Setting of left Bundle Branch Block: A Retrospective Case-control Study. Am Heart J. 2015;170(6):1255-64. doi: 10.1016/j.ahj.2015.09.005.</mixed-citation>
      </ref>
      <ref id="B61">
        <label>61</label>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Linde</surname>
              <given-names>JJ</given-names>
            </name>
            <name>
              <surname>Kelb&#230;k</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Hansen</surname>
              <given-names>TF</given-names>
            </name>
            <name>
              <surname>Sigvardsen</surname>
              <given-names>PE</given-names>
            </name>
            <name>
              <surname>Torp-Pedersen</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Bech</surname>
              <given-names>J</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2020</year>
          <volume>75</volume>
          <issue>5</issue>
          <fpage>453</fpage>
          <lpage>463</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jacc.2019.12.012</pub-id>
        </element-citation>
        <mixed-citation>61 Linde JJ, Kelb&#230;k H, Hansen TF, Sigvardsen PE, Torp-Pedersen C, Bech J, et al. Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome. J Am Coll Cardiol. 2020;75(5):453-63. doi: 10.1016/j.jacc.2019.12.012.</mixed-citation>
      </ref>
    </ref-list>
  </back>
  <sub-article article-type="translation" id="S01" xml:lang="en">
    <front-stub>
      <article-id pub-id-type="doi">10.36660/abc.20230733i</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Review Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Beyond STEMI-NSTEMI Paradigm: Dante Pazzanese's Proposal for Occlusion Myocardial Infarction Diagnosis</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>Writing of the manuscript</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Feres</surname>
            <given-names>Fausto</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff4">
            <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>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Franchini</surname>
            <given-names>Kleber Gomes</given-names>
          </name>
          <role>Acquisition of data</role>
          <role>Analysis and interpretation of the data</role>
          <role>Writing of the manuscript</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff4">
            <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>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Felicioni</surname>
            <given-names>Sandro Pinelli</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Analysis and interpretation of the data</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Costa</surname>
            <given-names>Ana Carolina Muniz</given-names>
          </name>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Fernandes</surname>
            <given-names>Rinaldo Carvalho</given-names>
          </name>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-4108-4653</contrib-id>
          <name>
            <surname>Ramadan</surname>
            <given-names>Hugo Ribeiro</given-names>
          </name>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Meyers</surname>
            <given-names>Pendell</given-names>
          </name>
          <role>Analysis and interpretation of the data</role>
          <role>Writing of the manuscript</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff5">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-9166-9804</contrib-id>
          <name>
            <surname>Smith</surname>
            <given-names>Stephen W.</given-names>
          </name>
          <role>Analysis and interpretation of the data</role>
          <role>Writing of the manuscript</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff6">
            <sup>3</sup>
          </xref>
        </contrib>
        <aff id="aff4">
          <label>1</label>
          <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">Brazil</country>
          <institution content-type="original">Instituto Dante Pazzanese de Cardiologia, S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff5">
          <label>2</label>
          <addr-line>
            <named-content content-type="city">Charlotte</named-content>
            <named-content content-type="state">NC</named-content>
          </addr-line>
          <country country="US">USA</country>
          <institution content-type="original">Carolinas Medical Center &#8211; Department of Emergency Medicine, Charlotte, NC &#8211; USA</institution>
        </aff>
        <aff id="aff6">
          <label>3</label>
          <addr-line>
            <named-content content-type="city">Minneapolis</named-content>
            <named-content content-type="state">MN</named-content>
          </addr-line>
          <country country="US">USA</country>
          <institution content-type="original">Hennepin Healthcare, Department of Emergency Medicine and University of Minnesota, Minneapolis, MN &#8211; USA</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><bold>Mailing Address: Jos&#233; Nunes De Alencar</bold> &#8226; Instituto Dante Pazzanese de Cardiologia - Avenida Dr. Dante Pazzanese, 500. Postal Code <postal-code>04012-091</postal-code>, Vila Mariana, S&#227;o Paulo, SP - Brazil E-mail: <email>jose.alencar@dantepazzanese.org.br</email> </corresp>
        <fn fn-type="edited-by">
          <p>Editor responsible for the review: Gl&#225;ucia Maria Moraes de Oliveira</p>
        </fn>
        <fn fn-type="conflict">
          <label> Potential conflict of interest </label>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Abstract</title>
        <p>Although the existing framework for classifying acute myocardial infarction (AMI) into STEMI and NSTEMI has been beneficial, it is now considered to be falling short in addressing the complexity of acute coronary syndromes.</p>
        <p>The study aims to scrutinize the current STEMI-NSTEMI paradigm and advocate for a more nuanced framework, termed as occlusion myocardial infarction (OMI) and non-occlusion myocardial infarction (NOMI), for a more accurate diagnosis and management of AMI.</p>
        <p>A comprehensive analysis of existing medical literature was conducted, with a focus on the limitations of the STEMI-NSTEMI model. The study also outlines a new diagnostic approach for patients presenting with chest pain in emergency settings.</p>
        <p>The traditional STEMI-NSTEMI model falls short in diagnostic precision and effective treatment, especially in identifying acute coronary artery occlusions. The OMI-NOMI framework offers a more anatomically and physiologically accurate model, backed by a wealth of clinical research and expert opinion. It underscores the need for quick ECG assessments and immediate reperfusion therapies for suspected OMI cases, aiming to improve patient outcomes.</p>
        <p>The OMI-NOMI framework offers a new avenue for future research and clinical application. It advocates for a more comprehensive understanding of the underlying mechanisms of acute coronary syndromes, leading to individualized treatment plans. This novel approach is expected to ignite further scholarly debate and research, particularly in the Brazilian cardiology sector, with the goal of enhancing diagnostic accuracy and treatment effectiveness in AMI patients.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>Electrocardiography</kwd>
        <kwd>Coronary Occlusion</kwd>
        <kwd>Myocardial Infarction</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>The diagnosis of acute myocardial infarction (AMI) is at a pivotal juncture. For many years, the (STEMI), (NSTEMI), STEMI-NSTEMI (ST-elevated myocardial infarction-non-ST elevated myocardial infarction) model has been fundamental in guiding urgent reperfusion treatments and directing medical professionals to treat acute coronary events. Although the model has significantly improved patient survival and quality of life, since the beginning of the Reperfusion Era at the end of the last century, its limitations in addressing the complexities of acute coronary conditions have been increasingly evident.</p>
        <p>In this article, Cardiologists from Instituto Dante Pazzanese de Cardiologia, in collaboration with the proponents of this new paradigm, present this statement, drawing parallels between current paradigms and seminal shifts in the literature. We question the prevailing STEMI-NSTEMI paradigm for AMI diagnosis, and we advocate for the terms occlusion myocardial infarction (OMI) and non-occlusion myocardial infarction (NOMI). Notably, in the Portuguese version of this paper, "oclus&#227;o coronariana aguda (OCA)" is the terminology used for OMI. We propose this concept as a more precise anatomical and physiological framework for managing and classifying AMI. We strongly advocate for this new perspective based on extensive clinical research, expert opinions, and our clinical experience. We aim to spark crucial discussions in the cardiology field in Brazil about updating strategies for AMI treatment.</p>
        <sec>
          <title>A brief history of the "STEMI" and "NSTEMI" paradigm</title>
          <p>Unfortunately, and unlike other diseases, AMI has thus far always been classified only according to individual electrocardiogram (ECG) findings rather than the underlying pathophysiology. Nevertheless, the STEMI-NSTEMI paradigm, which replaced the previous "Q-wave myocardial infarction" and "non-Q-wave myocardial infarction" terminology in 2000, marked a significant advancement in the era of reperfusion therapy. It enabled the early identification of patients at risk of myocardial death before the development of a Q wave. At that time, thrombolysis was the primary reperfusion method available. A meta-analysis from the early era of this therapy revealed a number needed to treat (NNT) of 56 for the use of fibrinolytics. Notably, four of these studies, including the ISIS-2 study, did not require ECG alterations for patient inclusion.<sup><xref ref-type="bibr" rid="B1">1</xref>&#8211;<xref ref-type="bibr" rid="B3">3</xref></sup> However, subgroup analyses found an association with ST-segment elevation (STE), poorly defined, and improved outcomes with thrombolytics (primarily streptokinase).</p>
          <fig id="f14">
            <graphic xlink:href="1678-4170-abc-121-05-e20230733-30733-gf01-en.tif"/></fig>
        </sec>
        <sec>
          <title>The false dichotomy of STEMI vs. NSTEMI: A growing body of evidence</title>
          <p>The STEMI paradigm was a significant milestone in cardiovascular medicine. However, the effort to standardize the STEMI criteria has exposed gaps with considerable consequences for patients.</p>
          <p>In an early attempt to reconcile various STE criteria, Menown et al.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> used logistic regression analysis in a case-control study of 1190 subjects to determine the optimal STE cut-offs: &#8805; 2 mm in at least one of the anteroseptal leads (V1&#8211;4) or &#8805; 1 mm in any other leads. This study relied on CK-MB to confirm myocardial infarction (MI), instead of angiographic evidence of acute coronary occlusion (ACO).<sup><xref ref-type="bibr" rid="B4">4</xref></sup> This methodological approach meant the study could not distinguish ACO from non-ACO, resulting in a sensitivity of only 56% for diagnosing AMI based on biomarkers.</p>
          <p>In 2004, Macfarlane et al.,<sup><xref ref-type="bibr" rid="B5">5</xref></sup> in a case-control study, suggested age and sex-specific STE cut-offs, applying analogous statistical techniques used in previous studies. However, the primary endpoint for diagnostic confirmation was again based on CK-MB values, ignoring the angiographic evidence of ACO.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Drawing from these case-control studies, the American Heart Association/American College of Cardiology Foundation/Heart Rhythm Society (AHA/ACCF/HRS) periodically redefines what is now known as the "STEMI criteria". This definition continues to be echoed in subsequent guidelines, including the 4th Universal Definition of MI.<sup><xref ref-type="bibr" rid="B6">6</xref></sup></p>
          <p>Shortly after the 2000 consensus was reached, doubts arose about the adequacy of the STEMI-NSTEMI paradigm. The label "STEMI" has inadvertently emphasized just one aspect of a diagnostic test&#8212; the presence of STE on the ECG.<sup><xref ref-type="bibr" rid="B7">7</xref>&#8211;<xref ref-type="bibr" rid="B9">9</xref></sup> Some physicians, possibly unaware of how the STEMI/NSTEMI paradigm originated, may mistakenly believe that patients with OMI, but lacking STE on their ECG, do not benefit from reperfusion therapy.</p>
          <p>In 2001, Schmitt et al.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> was among the first to study the STEMI-NSTEMI paradigm angiographically. They found that 29% of the 418 patients with ACO did not meet "STEMI criteria". In particular, 50% of ECGs of patients with acute left circumflex artery occlusion failed to meet criteria.<sup><xref ref-type="bibr" rid="B10">10</xref></sup></p>
          <p>In a post-hoc analysis of the PARAGON-B trial, 528 (27%) of 1,957 patients diagnosed with non-ST elevated acute coronary syndromes (NSTE-ACS) had fully occluded culprit vessels; these patients had larger infarct size and higher six-month risk-adjusted mortality.<sup><xref ref-type="bibr" rid="B11">11</xref></sup></p>
          <p>The TRITON-TIMI-38 study<sup><xref ref-type="bibr" rid="B12">12</xref></sup> provided additional evidence: of 1,198 patients with NSTE-ACS and isolated ST-segment depressions (STD), 314 (26.2%) had culprit arteries that were fully occluded. Koyama et al.<sup><xref ref-type="bibr" rid="B13">13</xref></sup> also contributed to this understanding, finding that in STEMI cases, 57% had TIMI-0 flow, while in NSTEMI cases, 47% had TIMI-0 flow, with both groups showing a mortality rate of around 5%.<sup><xref ref-type="bibr" rid="B13">13</xref></sup> This is evidence that NSTEMI with occluded coronary arteries are essentially equivalent to STEMI in terms of severity and outcomes.</p>
          <p>In 2021, Meyers et al.<sup><xref ref-type="bibr" rid="B14">14</xref></sup> compared the STEMI/NSTEMI paradigm to the OMI/NOMI framework. They aimed to identify differences in catheterization timing and related outcomes between STEMI(+) OMI and STEMI(-) OMI groups. The authors found that 28% of NSTEMI patients had total coronary occlusion detected at delayed catheterization and 45% of OMI did not meet STEMI criteria. Infarct size of these STEMI (-) OMI were statistically equal to those of the STEMI(+) OMI group.<sup><xref ref-type="bibr" rid="B14">14</xref></sup> In further research, Meyers et al.<sup><xref ref-type="bibr" rid="B15">15</xref></sup> examined the accuracy of specific OMI ECG markers compared to the current STEMI criteria. These predefined OMI ECG markers were far more sensitive while maintaining high specificity. These data suggest that accurate ECG interpretation can quickly and noninvasively identify patients with STEMI(-) OMI for immediate reperfusion.<sup><xref ref-type="bibr" rid="B15">15</xref></sup></p>
          <p>The 2020 DIFOCCULT study<sup><xref ref-type="bibr" rid="B16">16</xref></sup> provided still more compelling evidence. Cardiologists, using expert interpretation of the ECG rather than strict STEMI criteria, blindly reclassified 28% of patients with NSTEMI as OMI; these patients had significantly higher long-term mortality than NSTEMI patients classified by ECG as having NOMI. A meta-analysis of diagnostic test accuracy conducted by our team further elucidates the diagnostic challenges associated with this condition. We found that the pooled sensitivity of STE in detecting ACO was only 43.6% (95% CI: 34.7%-52.9%), suggesting that more than half of ACO cases may not have STE. Specificity was high, at 96.5% (95% CI: 91.2%&#8211;98.7%). Further analysis employing the OMI-NOMI strategy demonstrated an improved sensitivity of 78.1% (95% confidence interval [CI]: 62.7%&#8211;88.3%) while maintaining a similar specificity of 94.4% (95% CI: 88.6%&#8211;97.3%).<sup><xref ref-type="bibr" rid="B17">17</xref></sup></p>
          <p>In a meta-analysis of prevalence, Khan et al.<sup><xref ref-type="bibr" rid="B18">18</xref></sup> reported that 25% of 40,000 patients with NSTEMI were found to have an acutely occluded artery on next day angiogram without any collateral circulation. Compared to NSTEMI patients with an open artery, these individuals faced nearly double the mortality rate, even though they were, on average, 15 years younger and had fewer comorbidities.<sup><xref ref-type="bibr" rid="B18">18</xref></sup> In another meta-analysis by Hung et al.,<sup><xref ref-type="bibr" rid="B19">19</xref></sup> of 60,000 NSTEMI patients, 34% were later found to have total coronary occlusion. Compared to patients with an open artery, those with OMI had, adjusted for other clinical factors: lower ejection fraction, higher biomarkers, more cardiogenic shock, and higher mortality (OR 1.72, 95% CI 1.49-1.98, p &lt; 0.001).<sup><xref ref-type="bibr" rid="B19">19</xref></sup></p>
          <p>The STEMI-NSTEMI paradigm, by defining a disease by one very inaccurate aspect (STE) of one test (the ECG), overlooks the actual pathophysiology of ACO. This results in the "No False Negative Paradox:" if a patient has ACO but no STE, there is no STEMI and so there is no false negative test for STEMI. This has resulted in the exclusion of STEMI (-) OMI patients from STEMI databases, and thus in limited standardized data on the sensitivity and specificity of STE for diagnosing OMI. This data gap in the literature hinders clinical decision-making, as physicians must use potentially inadequate criteria to address acute coronary syndrome (ACS).</p>
        </sec>
        <sec>
          <title>Urgency of Treatment in Occluded Coronary Arteries: Time is Myocardium</title>
          <p>In ACS, the saying "time is myocardium" holds true for OMI patients. For them, waiting is not an option; immediate reperfusion therapy is imperative. Troponin levels, while commonly used to diagnose MI, are not effective in diagnosing OMI in the acute settings for the following reasons:</p>
          <list list-type="bullet">
            <list-item>
              <p>Time delay: Troponin results are not instantaneous; they take time both to acquire (blood draw) and to process, during which the myocardium is at risk;</p>
            </list-item>
            <list-item>
              <p>Lack of sensitivity: the initial high-sensitivity (hs) troponin lacks adequate sensitivity for acute OMI; in one study, the initial hs-troponin I was less sensitive than the rule-in threshold (52 ng/L) for type 1 MI in 27% of STEMI.<sup><xref ref-type="bibr" rid="B20">20</xref></sup> In a second real world population, the initial troponin value was below the upper reference limit in 47% of STEMI.<sup><xref ref-type="bibr" rid="B21">21</xref></sup> Moreover, troponin does not distinguish myocardial injury from AMI, type I MI from type II MI, nor OMI from NOMI. Consequently, hs-troponin is an unreliable marker for immediate clinical decision-making.</p>
            </list-item>
          </list>
          <p>Perhaps the most common objection to the fact that NSTEMI-OMI [STEMI (-) OMI)] require emergent reperfusion comes from randomized trials comparing immediate vs. delayed interventions in patients with NSTEMI, showing no benefit. However, these studies are widely misrepresented. The most notable of these trials is the TIMACS study.<sup><xref ref-type="bibr" rid="B22">22</xref></sup> In this study, the "early intervention" group had a median intervention time of 16 hours, too prolonged to offer any benefit to patients with OMI. Furthermore, TIMACS did not include patients with ongoing symptoms. However, all studies that defined early intervention as less than two hours and included patients with ongoing symptoms demonstrated the benefit of an early intervention.<sup><xref ref-type="bibr" rid="B22">22</xref>&#8211;<xref ref-type="bibr" rid="B29">29</xref></sup></p>
          <p>Furthermore, the TIMACS study and others are often mischaracterized as involving only NSTEMI patients. However, this and other similar studies also enrolled patients without elevated troponin, who therefore, by definition, had unstable angina (UA), not AMI. It is well known that elevated troponin is a powerful predictor of high risk in ACS. In the case of TIMACS, 22% of the 3031 patients were diagnosed with UA, not AMI. It is worth noting that patients with serial negative troponins, indicative of UA, have never been shown to benefit from emergent rather than delayed treatment. How could more rapid reperfusion lead to reduced infarct size, when there is no infarct at all? Consequently, the lack of a noticeable difference in the primary outcome is not surprising, since 22% of the study population had no plausible mechanism of benefit.</p>
          <p>Although the "early" intervention group in TIMACS waited an average of 16 hours for catheterization, there was a notable trend towards benefit in the primary outcome, with a 2.1% absolute risk reduction in death, MI, or stroke (9.4% vs. 11.5%, RR 0.81, 95%CI 0.63-1.04). This was observed despite the longer wait time for the "early" intervention group and the inclusion of 22% of patients with UA. Furthermore, the subgroup with a GRACE score &gt; 140 showed benefits in all outcomes.</p>
          <p>A subsequent important trial, frequently cited by those who claim no advantage over earlier NSTEMI management, is the VERDICT trial.<sup><xref ref-type="bibr" rid="B29">29</xref></sup> Among the 2,147 patients enrolled, 80% were diagnosed with NSTEMI, while 20% had UA without AMI. Again, the inclusion of UA dilutes the results. Adhering to all guidelines, the study excluded patients experiencing ongoing pain. In VERDICT, the angiogram times for the early and delayed groups were 4.7 and 62 hours, respectively. Although 4.7 hours is a significant improvement from the 16-hour duration observed in the early group of TIMACS, it remains a considerable delay in ACO-MI treatment, a fact readily acknowledged in the context of "STEMI" management. The primary outcome, which considered the potential benefits of rapid angiogram for a cohort comprising asymptomatic NSTEMIs and asymptomatic UA patients with serial negative troponins, unsurprisingly did not produce a discernible advantage for the early group.</p>
          <p>However, like the TIMACS trial,<sup><xref ref-type="bibr" rid="B22">22</xref></sup> the VERDICT<sup><xref ref-type="bibr" rid="B29">29</xref></sup> subgroup with a GRACE score greater than 140 showed significant benefits in the primary outcome. Further examination of the NSTEMI patient subgroup revealed a 4% absolute reduction in the primary composite outcome (death, AMI, and repeated admission for ischemia or heart failure). This difference was not statistically significant, as the study could not discern a 4% variation (28.8% vs 32.7%, RR 0.85, 95% CI 0.71-1.01). An intervention demonstrating a reduction in absolute risk of 4% (NNT=25) in such a patient-centered outcome would hold significant clinical relevance if validated by a sufficiently powered study. So, the VERDICT findings cannot definitively counter this proposition.</p>
          <p>Thus, the most extensive and pertinent studies<sup><xref ref-type="bibr" rid="B22">22</xref>,<xref ref-type="bibr" rid="B29">29</xref></sup> consistently indicate significant benefits in high-risk NSTEMI subgroups. These studies also suggest that the benefits observed in the entire NSTEMI subgroup could be confirmed if they were sufficiently powered. These findings come from populations where patients reported to be asymptomatic. Furthermore, the intervention times in the early management groups, 16 hours<sup><xref ref-type="bibr" rid="B22">22</xref></sup> and 4.7 hours<sup><xref ref-type="bibr" rid="B29">29</xref></sup> were substantially longer than what is typically considered emergent management (defined as less than 90 minutes). In fact, another trial, the RIDDLE-NSTEMI, where the time to percutaneous coronary intervention (PCI) was genuinely early (1.4 hours), demonstrated that an immediate invasive strategy in NSTEMI patients is associated with lower rates of death or new MI compared with a delayed invasive strategy.<sup><xref ref-type="bibr" rid="B30">30</xref></sup> This discrepancy hints at the potential for even more benefits if the intervention had been genuinely emergent, and especially if the study had been limited to OMI patients who are NSTEMI with specific ECG findings and usually with ongoing symptoms (e.g., persistent chest pain). Thus, our position is not to advocate for the emergent management of all NSTEMIs, especially those with resolved symptoms. Instead, we emphasize the importance of recognizing and promptly addressing the highest risk NSTEMI subgroup: OMI patients. These individuals, who have acutely occluded or nearly occluded culprit vessels, can gain the most from emergent management. The vast majority can be identified by the ECG using features beyond ST Elevation.</p>
          <p>Given the critical anatomical reality of an occluded artery, it is recommended that the reperfusion therapy timeframe for OMI patients align with the door-to-needle and door-to-balloon time standards set for STEMI patients. Any delay in pursuing diagnostic clarity can lead to irreversible myocardial damage and negatively impact outcomes.</p>
        </sec>
        <sec>
          <title>The new paradigm: OMI-NOMI</title>
          <p>Given the limitations inherent in the STEMI-NSTEMI paradigm, a more nuanced approach has been proposed, focusing on the anatomical and physiological intricacies of ACS. This revised paradigm distinguishes patients into two categories:</p>
          <list list-type="bullet">
            <list-item>
              <p>OMI: This designation applies to patients experiencing ACO or near-occlusion, with limited collateral circulation, placing them at immediate risk of transmural AMI. This condition predominantly causes type 1 MI. The need for reperfusion therapy for these patients is urgent, regardless of the ECG findings. The primary concern is the anatomical obstruction and its associated risk, rather than the specifics of the ECG criteria. Although ECG findings play a role, other clinical and diagnostic findings, such as echocardiographic wall motion abnormalities or vessel obstruction detected by computed tomography coronary angiogram, can aid in diagnosing OMI, especially if the ECG is inconclusive.</p>
            </list-item>
            <list-item>
              <p>NOMI: This category includes patients without coronary occlusion. However, because NOMI may involve unstable ruptured plaque, they remain vulnerable to potential coronary thrombosis and ischemia. These patients may have elevated troponin levels or ECG changes, such as T-wave inversions. Although these patients need an angiogram and intervention if a culprit is found, immediate reperfusion therapy is not typically warranted for this group. ECG is not sensitive for NOMI but, fortunately, it need not be because immediate intervention is not needed, and the diagnosis can wait for troponin.</p>
            </list-item>
          </list>
          <p>This revised framework seeks to enhance our comprehension and handling of ACS. It prompts clinicians to emphasize not just the ECG, but also the underlying pathophysiology, thus aligning treatments more closely with individual patient requirements (Central figure). Meyers and Smith first championed this paradigm in their "OMI Manifesto", which presents a significant direction for impending research and clinical application.</p>
          <p>Advancements in technology have significantly influenced the refinement of AMI management. Emerging artificial intelligence algorithms exhibit high precision in diagnosing OMI and are rapidly evolving. Such advancements could enhance the OMI-NOMI paradigm, providing clinicians with even more precise diagnostic tools.<sup><xref ref-type="bibr" rid="B31">31</xref>,<xref ref-type="bibr" rid="B32">32</xref></sup></p>
        </sec>
        <sec>
          <title>Other electrocardiographic signs of OMI</title>
          <p>In the evolving landscape of OMI diagnosis, one of the key electrocardiographic signs is the hyperacute T-wave, characterized by increased area under the T wave relative to the QRS complex, including a broad base, increased length convexity, and a tendency towards symmetry. Visually, it appears as if the T-wave expands in all directions&#8212;towards the QRS complex, away from it, and upwards&#8212;resulting in a broadening of the QT interval and a more rounded peak (<xref ref-type="fig" rid="f8">Figure 1</xref>).</p>
          <fig id="f8">
            <label>Figure 1</label>
            <caption>
              <title>Hyperacute T waves; electrocardiogram at 25 mm/s showing a hyperacute T-wave in leads V2-V4.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-121-05-e20230733-30733-gf02-en.tif"/></fig>
          <p>Inverted T-waves are not indicative of hyperacute phases of infarction, as some might assume from the term "sub-epicardial ischemia". Inverted T-waves recorded by leads overlying the ischemic myocardium appear after acute reperfusion, and in sub-acute or chronic ischemic states, or as reciprocal to hyperacute T-waves in an opposing lead. When negative T-waves are present, the issue may not be located in the sub-epicardial zone of the overlying leads, but may be located in zones of distant, opposite myocardium.</p>
          <p>In addition to these signs, the De Winter pattern is noteworthy. This pattern is estimated to occur in only about 2% of patients with anteroapical MI undergoing primary angioplasty. In the clinical context of acute ischemic chest pain, the De Winter ECG pattern exhibits a STD measured at the J point of at least 1 mm in leads V1-V2 to V6 followed by an usually upslope ST segment and a high, symmetrical, and positive hyperacute T wave (<xref ref-type="fig" rid="f9">Figure 2</xref>). Although de Winter T-waves receive a lot of attention, they have no more importance than other hyperacute T-wave, of which they comprise only a small fraction.</p>
          <fig id="f9">
            <label>Figure 2</label>
            <caption>
              <title>Subtle De Winter sign; electrocardiogram at 25 mm/s displaying the De Winter pattern, characterized by ST-segment depression at the J point in leads V1-V2 to V6, followed by an upsloping ST segment and a high, symmetrical, positive hyperacute T wave.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-121-05-e20230733-30733-gf03-en.tif"/></fig>
          <p>Transitioning from T-waves, terminal QRS distortion offers another diagnostic clue. Defined as the absence of an S-wave below the TP isoelectric line and the absence of a J-wave in leads V2 or V3, it is very specific finding for left anterior descending artery (LAD) when compared to early repolarization.<sup><xref ref-type="bibr" rid="B33">33</xref></sup> To differentiate physiological and ischemic STE in V2 and V3, the four-variable Smith's formula might be used, with 88.8% sensitivity and 94.7% specificity (<xref ref-type="fig" rid="f10">Figure 3</xref>).<sup><xref ref-type="bibr" rid="B34">34</xref>,<xref ref-type="bibr" rid="B35">35</xref></sup> The calculator is available in: Subtle Anterior STEMI Calculator (4-Variable) (mdcalc.com)</p>
          <fig id="f10">
            <label>Figure 3</label>
            <caption>
              <title>Subtle ST segment elevation in anteroapical wall; electrocardiogram displaying a subtle STE of approximately 1 mm in V1-V4, which does not fulfil the criteria set by the Universal Definition of Myocardial Infarction. The use of the 4-variable calculator indicated Occlusion Myocardial Infarction (OMI). Subsequent coronary angiography confirmed occlusion of the left anterior descending artery.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-121-05-e20230733-30733-gf04-en.tif"/></fig>
          <p>Another electrocardiographic sign of OMI is the Aslanger pattern, which is associated with inferior wall infarction and multi-vessel coronary artery disease (CAD), not meeting the classical criteria for STE in two contiguous leads. It is characterized by STE in lead III only, and STD in any of the leads V4-V6 but not in V2, and an ST segment in V1 that is greater than in V2.<sup><xref ref-type="bibr" rid="B36">36</xref></sup></p>
          <p>Another ECG sign of OMI involves occlusion of the diagonal branch, affecting the anteromedial wall of the heart. According to the current terminology for MI walls, which is based on magnetic resonance, leads I, aVL, and V2&#8212;and occasionally V3&#8212;correspond to the anteromedial wall of the left ventricle. In some cases, STE may only be evident in aVL and V2.<sup><xref ref-type="bibr" rid="B37">37</xref>,<xref ref-type="bibr" rid="B38">38</xref></sup> This region is supplied by the first diagonal branch of the LAD artery. A lack of awareness of this terminology could mislead cardiologists into thinking that aVL and V2 are not contiguous leads. When these leads are affected, a reciprocal change often occurs in the inferior wall, particularly in lead III. This specific pattern has been termed the "South African Flag" pattern.</p>
          <p>The inverse also appears to be true: any ST depression in aVL is helpful to diagnose inferior wall OMI versus pericarditis. A study involving 426 patients with inferior MI and normal QRS complex found that 99% of ischemic inferior STEs exhibited some degree of reciprocal STD in lead aVL. This was true even when the inferior STE was subtle (less than 1 mm) and when there was STE in leads V5 and V6. In contrast, pericarditis showed no STD in any lead except aVR.<sup><xref ref-type="bibr" rid="B39">39</xref></sup> Another important change to consider is STD in leads V1 to V3/V4, which serves as a reciprocal indicator of STE in leads V7 to V9, corresponding to the lateral wall of the heart<sup><xref ref-type="bibr" rid="B31">31</xref>,<xref ref-type="bibr" rid="B40">40</xref>,<xref ref-type="bibr" rid="B41">41</xref></sup></p>
          <p>The diagnosis of AMI becomes particularly challenging when a patient presents with left bundle branch block (LBBB).<sup><xref ref-type="bibr" rid="B42">42</xref></sup> The 2013 ACC/AHA guidelines and the 2017<sup><xref ref-type="bibr" rid="B43">43</xref></sup> and 2023 ESC STEMI guidelines<sup><xref ref-type="bibr" rid="B44">44</xref></sup> recommend that patients with clinical suspicion of ongoing myocardial ischemia and LBBB should be managed irrespective of whether the LBBB is previously known. Importantly, the guidelines emphasize that the presence of a new or presumably new LBBB does not, by itself, predict an MI.<sup><xref ref-type="bibr" rid="B43">43</xref>&#8211;<xref ref-type="bibr" rid="B45">45</xref></sup> Sgarbossa et al.<sup><xref ref-type="bibr" rid="B46">46</xref></sup> proposed a scoring system that was further refined by introducing a proportional criterion, known as the Smith-modified Sgarbossa criteria, which is also validated for ventricular paced rhythm.<sup><xref ref-type="bibr" rid="B47">47</xref>,<xref ref-type="bibr" rid="B48">48</xref></sup></p>
          <p>According to the Fourth Universal Definition of MI,<sup><xref ref-type="bibr" rid="B6">6</xref></sup> new or presumably new RBBB without associated ST-segment or T-wave changes should be considered as a STEMI-equivalent ECG. These recommendations are primarily based on a retrospective study by Widimsky et al.,<sup><xref ref-type="bibr" rid="B49">49</xref></sup> which included 6,742 patients with acute MI.<sup><xref ref-type="bibr" rid="B49">49</xref></sup> In that study, not all participants underwent emergency angiography as a primary PCI protocol. Other evidences challenge the notion of RBBB as an indicator of emergency coronary angiography, as the likelihood of MI was similar to that of patients without any block.<sup><xref ref-type="bibr" rid="B50">50</xref></sup> Hence, further outcome data are needed for patients presenting with chest pain, presumably new RBBB, and no significant ST deviation.</p>
          <p>To provide a succinct overview of the various signs and findings discussed, <xref ref-type="fig" rid="f11">Figure 4</xref> will summarize these elements for reference and better understanding.</p>
          <fig id="f11">
            <label>Figure 4</label>
            <caption>
              <title>Key electrocardiographic indicators for occlusion myocardial infarction.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-121-05-e20230733-30733-gf05-en.tif"/></fig>
        </sec>
        <sec>
          <title>Current guidelines and their binary approach to acute MI diagnosis</title>
          <p>The current guidelines for the management of AMI are meticulously crafted, serving as the foundation for treating of thousands of patients by cardiologists and general practitioners. These guidelines dictate that if a patient with OMI, but without ECG criteria for STEMI, arrives at the emergency department, it is unlikely that this patient will undergo urgent catheterization within the door-to-balloon time that is recommended for STEMI.<sup><xref ref-type="bibr" rid="B51">51</xref></sup> Instead, clinicians typically order a troponin test, which can take 1 to 2 hours to yield results. During this interval, patient often receive antianginal medications, including morphine. Although new point-of-care hs-troponins provide quick results,<sup><xref ref-type="bibr" rid="B52">52</xref></sup> an elevated troponin level confirms an AMI. If the clinical history is suggestive of type 1 MI, troponin still does not differentiate between OMI and NOMI. When the troponin level increases sufficiently to indicate OMI, substantial irreversible myocardial injury has already occurred, and the critical window for door-to-needle or door-to-balloon time has often closed. Thus, an OMI diagnosis should be determined before troponin results are available through expert ECG interpretation or application of artificial intelligence to the ECG. Morphine obscures the diagnosis by leading to a false sense of security, as the patient is apparently pain free (but not ischemia-free); thus, the use of morphine may be associated with prolonged times to angiography.<sup><xref ref-type="bibr" rid="B53">53</xref></sup></p>
          <p>The Brazilian guidelines for MI without STE recommend urgent invasive strategies for patients who experience refractory or recurrent chest pain.<sup><xref ref-type="bibr" rid="B33">33</xref></sup> This approach is designed to serve as a safety net for OMI patients who do not meet ECG criteria for STEMI. Catheterization is advised if a patient has a false-negative ECG but continues to experience chest pain. Although this recommendation is highly prudent, it is worth noting that its implementation is not as widespread as one might expect, even in settings where it is officially endorsed.<sup><xref ref-type="bibr" rid="B51">51</xref></sup></p>
          <p>In OMI, the initial troponin can either be positive or negative, similar to some obvious STEMI cases. Often, catheterization for NSTEMI is deferred to a later date. In more fortunate situations, it might take place later on the same day. However, both scenarios do not align with the timeframes recommended by current guidelines (<xref ref-type="fig" rid="f12">Figure 5</xref>).</p>
          <fig id="f12">
            <label>Figure 5</label>
            <caption>
              <title>Flowchart illustrating the current approach for acute myocardial infarction diagnosis; this has been the cornerstone for the treatment of numerous patients across various medical disciplines; the algorithm addresses the limitations of relying solely on electrocardiogram and troponin test results.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-121-05-e20230733-30733-gf06-en.tif"/></fig>
          <p>We appreciate the thoughtfulness and rigor in the development of these guidelines. However, we believe that there is an opportunity for more assertive action in this area. We advocate for the introduction of a new paradigm for approaching MI. This paradigm aims to be both more inclusive and accurate, providing a better framework for cardiologists, general practitioners, and medical students in the future.</p>
        </sec>
        <sec>
          <title>Our proposed approach for chest pain patients in the emergency department: the OMI-NOMI paradigm</title>
          <p>In addressing the urgent need for a precise and rapid diagnosis of AMI, we propose a refined approach that emphasizes the differentiation between OMI and NOMI. If a patient with epidemiological risk factors presents to the emergency department with anginal pain (or other ischemic symptoms), the patient should be immediately evaluated for potential OMI (<xref ref-type="fig" rid="f14">Central Illustration</xref>). This approach is designed to be both practical and effective, acknowledging the inherent complexities and limitations in diagnosing AMI.</p>
          <p>Step-by-step diagnostic process:</p>
          <list list-type="order">
            <list-item>
              <p>Immediate ECG assessment: upon arrival at the emergency department, patients presenting with epidemiological risk factors and symptoms suggestive of ischemia (anginal pain or equivalents) should undergo an ECG within the first 10 minutes. This prompt evaluation is crucial in identifying potential cases of OMI.</p>
            </list-item>
            <list-item>
              <p>Searching for STE in ECG: a key step in the evaluation of a patient with suspected AMI in the emergency department is the assessment of the STE on the ECG. While the presence of significant STE is a strong indicator of OMI, it is crucial to understand that approximately 30-50% of OMI cases may not exhibit this classic sign. This highlights the importance of not solely relying on STE for diagnosing OMI. Clinicians must be aware of this possibility and be prepared to investigate further, even in the absence of significant STE, to ensure that cases of OMI are not overlooked.</p>
            </list-item>
            <list-item>
              <p>Looking for other signs of OMI: in addition to assessing for STE, clinicians should be vigilant in identifying other electrocardiographic indicators that may suggest OMI:<sup><xref ref-type="bibr" rid="B54">54</xref>,<xref ref-type="bibr" rid="B55">55</xref></sup> Subtle STE &lt; 1 mm is frequently seen in acute OMI, and any STE of &#8805; 1 mm in V2-V4 can be either normal or due to LAD artery OMI; use the four-variable formula to differentiate;<sup><xref ref-type="bibr" rid="B34">34</xref></sup> hyperacute T-waves with subtle STE or without any STE at all,<sup><xref ref-type="bibr" rid="B56">56</xref></sup> De Winter's sign,<sup><xref ref-type="bibr" rid="B57">57</xref>,<xref ref-type="bibr" rid="B58">58</xref></sup> Aslanger's pattern,<sup><xref ref-type="bibr" rid="B36">36</xref>,<xref ref-type="bibr" rid="B59">59</xref>,<xref ref-type="bibr" rid="B60">60</xref></sup> any STD in V1-V4 representing reciprocal changes from lateral wall (V7-V9),<sup><xref ref-type="bibr" rid="B41">41</xref></sup> terminal QRS distortion,<sup><xref ref-type="bibr" rid="B33">33</xref></sup> any STE in inferior leads accompanied by any STD in aVL indicative of reciprocal changes from the mid-anterior wall,<sup><xref ref-type="bibr" rid="B39">39</xref></sup> Smith's modified Sgarbossa criteria in instances of LBBB<sup><xref ref-type="bibr" rid="B47">47</xref>,<xref ref-type="bibr" rid="B61">61</xref></sup> or paced rhythm.<sup><xref ref-type="bibr" rid="B48">48</xref></sup> The presence of any of these signs necessitates immediate reperfusion. It is crucial to recognize that an OMI can occur even without these specific ECG signs, or even with a completely normal ECG.</p>
            </list-item>
            <list-item>
              <p>Serial ECGs and comparison: In the absence of clear ECG signs of OMI, serial ECGs should be performed, and previous ECGs should be obtained for comparison. This step is vital in identifying dynamic changes that may indicate evolving myocardial ischemia.</p>
            </list-item>
            <list-item>
              <p>Patients should receive antianginal treatment. Opioid pain relief should be avoided until the patient is committed to the cath lab, as it will hide ischemic symptoms. A patient with persistent chest pain in ACS requires an urgent invasive approach, even in the absence of ECG signs of OMI. Concurrently, it is essential to evaluate other potential causes of chest pain that may not respond to antianginal therapy (<xref ref-type="fig" rid="f13">Figure 6</xref>).</p>
            </list-item>
          </list>
          <fig id="f13">
            <label>Figure 6</label>
            <caption>
              <title>Proposed decision algorithm for managing chest pain in the emergency department. This flowchart outlines a comprehensive approach for the evaluation and management of patients presenting with chest pain in the emergency department. The algorithm incorporates both traditional and nuanced diagnostic criteria, aiming to improve the identification and treatment of Occlusion Myocardial Infarction (OMI). Key steps include initial clinical assessment, rapid electrocardiogram (ECG) evaluation, and consideration of both ST-segment elevation (STE) and other ECG signs. The algorithm also accounts for the possibility of false-negative OMI cases, emphasizing the importance of monitoring for refractory chest pain or dynamic changes in ECG as indicators for immediate reperfusion therapy. It is important to note that while this proposed algorithm offers a potential advancement in the management of chest pain, its implementation on a national scale, particularly within Brazil's Universal Healthcare System, may lead to an increase in the number of primary percutaneous coronary interventions. Therefore, the logistics and economic implications of this proposal should be carefully considered, and further validated through randomized controlled trials before widespread adoption.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-121-05-e20230733-30733-gf07-en.tif"/></fig>
          <p>Beyond ischemic symptoms, repeat ECGs, and troponin levels, various diagnostic tools can serve as supplementary indicators to identify OMI. Typically, echocardiography reveals a wall motion abnormality during an OMI, but bubble contrast, excellent technique, and experienced interpretation is necessary for high sensitivity. Finally, an emergency coronary CT angiogram should be easily accessible and analogous to the current approach to assessing acute stroke patients within the "large vessel occlusion" framework.<sup><xref ref-type="bibr" rid="B61">61</xref></sup></p>
          <p>While this approach aims to provide a clear and viable pathway for diagnosing AMI, we acknowledge that no diagnostic method is infallible. The complexity of AMI presentations means that there will always be cases where the diagnosis is not immediately clear. Our approach is designed to maximize diagnostic accuracy while being adaptable to the nuances of individual patient presentations.</p>
        </sec>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclusion</title>
        <p>The AMI diagnosis landscape is poised for a paradigm shift. While the STEMI-NSTEMI framework has served us well as a transition out of the Reperfusion Era, mounting evidence and clinical observations indicate its limitations in addressing the intricate details of ACS. This article highlights these constraints and presents the OMI-NOMI paradigm as a more anatomically and physiologically accurate strategy for managing AMI. We anticipate that this refined approach will enhance patient outcomes by optimizing diagnostic accuracy and maximizing the efficacy of reperfusion therapies.</p>
        <p>We have presented evidence challenging the diagnostic and therapeutic accuracy of the STEMI-NSTEMI paradigm, underscoring the notable rate of overlooked occlusion myocardial infarctions and the constraints of relying solely on the ECG (and especially on STE) and troponin levels for prompt clinical decisions. Additionally, we outline Instituto Dante Pazzanese's approach to diagnosing patients with chest pain in the emergency setting, stressing the importance of rapid evaluation of the ECG and immediate reperfusion therapy for potential cases of OMI.</p>
        <p>We believe that the OMI-NOMI paradigm provides a promising direction for future research and clinical practice. It prompts clinicians to complement traditional diagnostic tests with a deeper understanding of the underlying pathophysiology of the ACS, leading to more tailored treatments to individual patient needs. We anticipate this article will stimulate further discussion and investigation within the Brazilian cardiology community, ultimately enhancing diagnostic precision and treatment efficacy for patients with AMI.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="financial-disclosure">
          <label> Sources of funding </label>
          <p>There were no external funding sources for this study.</p>
        </fn>
        <fn fn-type="other" id="fn5">
          <label> Study association </label>
          <p>This study is not associated with any thesis or dissertation work.</p>
        </fn>
        <fn fn-type="other" id="fn6">
          <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-group>
    </back>
  </sub-article>
</article>
