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  <front>
    <journal-meta>
      <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-loc>S&#227;o Paulo, SP, Brazil</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">tp4hwMzTn7ghTMr6RHBX5Fc</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2013002900002</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(13)10100300002</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20130163</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Valida&#231;&#227;o prospectiva do escore de risco dante pazzanese em s&#237;ndrome coronariana aguda sem supradesnivelamento do segmento ST</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Santos</surname>
            <given-names>Elizabete Silva dos</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Minuzzo</surname>
            <given-names>Luiz</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Souza</surname>
            <given-names>Roberta de</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Timerman</surname>
            <given-names>Ari</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">S&#227;o Paulo</named-content>
        </addr-line>
        <institution content-type="orgname">Instituto Dante Pazzanese de Cardiologia</institution>
        <country country="BR">Brazil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>09</month>
        <year>2013</year>
      </pub-date>
      <volume>101</volume>
      <issue>3</issue>
      <fpage>197</fpage>
      <lpage>204</lpage>
      <history>
        <date date-type="received">
          <day>13</day>
          <month>01</month>
          <year>2013</year>
        </date>
        <date date-type="accepted">
          <day>14</day>
          <month>05</month>
          <year>2013</year>
        </date>
        <date date-type="rev-recd">
          <day>11</day>
          <month>05</month>
          <year>2013</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/" xml:lang="en">
          <license-p>This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.</license-p>
        </license>
      </permissions>
      <abstract>
        <p>FUNDAMENTO: Em S&#237;ndrome Coronariana Aguda (SCA) sem Supradesnivelamento do segmento ST (SST) &#233; importante estimar a probabilidade de eventos adversos. Para esse fim, as diretrizes recomendam modelos de estratifica&#231;&#227;o de risco. O escore de risco Dante Pazzanese (escore DANTE) &#233; um modelo simples de estratifica&#231;&#227;o de risco, composto das vari&#225;veis: aumento da idade (0 a 9 pontos); antecedente de diabete melito (2 pontos) ou acidente vascular encef&#225;lico (4 pontos); n&#227;o uso de inibidor da enzima conversora da angiotensina (1 ponto); eleva&#231;&#227;o da creatinina (0 a 10 pontos); combina&#231;&#227;o de eleva&#231;&#227;o da troponina e depress&#227;o do segmento ST (0 a 4 pontos). OBJETIVO: Validar o escore DANTE em pacientes com SCA sem SST. M&#201;TODOS: Estudo prospectivo, observacional, com inclus&#227;o de 457 pacientes, de setembro de 2009 a outubro de 2010. Os pacientes foram agrupados em: muito baixo, baixo, intermedi&#225;rio e alto risco de acordo com a pontua&#231;&#227;o do modelo original. A habilidade preditiva do escore foi avaliada pela estat&#237;stica-C. RESULTADOS: Foram 291 (63,7%) homens e a m&#233;dia da idade 62,1 anos (11,04). Dezessete pacientes (3,7%) apresentaram o evento de morte ou (re)infarto em 30 dias. Ocorreu aumento progressivo na propor&#231;&#227;o do evento, com aumento da pontua&#231;&#227;o: muito baixo risco = 0,0%; baixo risco = 3,9%; risco intermedi&#225;rio = 10,9%; alto risco = 60,0%; p &lt; 0,0001. A estat&#237;stica-C foi de 0,87 (IC 95% 0,81-0,94; p &lt; 0,0001). CONCLUS&#195;O: O escore DANTE apresentou excelente habilidade preditiva para ocorr&#234;ncia dos eventos espec&#237;ficos e pode ser incorporado na avalia&#231;&#227;o progn&#243;stica de pacientes com SCA sem SST.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>S&#237;ndrome Coronariana Aguda</kwd>
        <kwd>Estudos de Valida&#231;&#227;o</kwd>
        <kwd>Pontua&#231;&#227;o de Propens&#227;o</kwd>
        <kwd>Risco</kwd>
        <kwd>Probabilidade</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>14</day>
        <month>08</month>
        <year>2013</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>Valida&#231;&#227;o prospectiva do escore de risco dante pazzanese em s&#237;ndrome coronariana aguda sem supradesnivelamento do segmento ST</bold>
    </p>
    <p>
      <bold>Elizabete Silva dos Santos; Luiz Minuzzo; Roberta de Souza; Ari Timerman</bold>
    </p>
    <p>Instituto Dante Pazzanese de Cardiologia, S&#227;o Paulo, SP - Brasil</p>
    <p>
      <xref ref-type="corresp" rid="enda">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>FUNDAMENTO:</bold> Em S&#237;ndrome Coronariana Aguda (SCA) sem Supradesnivelamento do segmento ST (SST) &#233; importante estimar a probabilidade de eventos adversos. Para esse fim, as diretrizes recomendam modelos de estratifica&#231;&#227;o de risco. O escore de risco Dante Pazzanese (escore DANTE) &#233; um modelo simples de estratifica&#231;&#227;o de risco, composto das vari&#225;veis: aumento da idade (0 a 9 pontos); antecedente de diabete melito (2 pontos) ou acidente vascular encef&#225;lico (4 pontos); n&#227;o uso de inibidor da enzima conversora da angiotensina (1 ponto); eleva&#231;&#227;o da creatinina (0 a 10 pontos); combina&#231;&#227;o de eleva&#231;&#227;o da troponina e depress&#227;o do segmento ST (0 a 4 pontos). </p>
    <p><bold>OBJETIVO:</bold> Validar o escore DANTE em pacientes com SCA sem SST. </p>
    <p><bold>M&#201;TODOS:</bold> Estudo prospectivo, observacional, com inclus&#227;o de 457 pacientes, de setembro de 2009 a outubro de 2010. Os pacientes foram agrupados em: muito baixo, baixo, intermedi&#225;rio e alto risco de acordo com a pontua&#231;&#227;o do modelo original. A habilidade preditiva do escore foi avaliada pela estat&#237;stica-C. </p>
    <p><bold>RESULTADOS:</bold> Foram 291 (63,7%) homens e a m&#233;dia da idade 62,1 anos (11,04). Dezessete pacientes (3,7%) apresentaram o evento de morte ou (re)infarto em 30 dias. Ocorreu aumento progressivo na propor&#231;&#227;o do evento, com aumento da pontua&#231;&#227;o: muito baixo risco = 0,0%; baixo risco = 3,9%; risco intermedi&#225;rio = 10,9%; alto risco = 60,0%; p &lt; 0,0001. A estat&#237;stica-C foi de 0,87 (IC 95% 0,81-0,94; p &lt; 0,0001). </p>
    <p><bold>CONCLUS&#195;O:</bold> O escore DANTE apresentou excelente habilidade preditiva para ocorr&#234;ncia dos eventos espec&#237;ficos e pode ser incorporado na avalia&#231;&#227;o progn&#243;stica de pacientes com SCA sem SST. </p>
    <p><bold>Palavras-chave:</bold> S&#237;ndrome Coronariana Aguda / diagn&#243;stico, Estudos de Valida&#231;&#227;o, Pontua&#231;&#227;o de Propens&#227;o, Risco, Probabilidade.</p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p>As doen&#231;as cardiovasculares constituem importante causa de &#243;bito em todo o mundo. Geralmente, esse conjunto de doen&#231;as representa a primeira causa de &#243;bito n&#227;o apenas nos pa&#237;ses desenvolvidos, mas tamb&#233;m naqueles em desenvolvimento<sup>1</sup>. Em decorr&#234;ncia da natureza heterog&#234;nea de pacientes com S&#237;ndrome Coronariana Aguda (SCA) sem Supradesnivelamento do segmento ST (SST) (angina inst&#225;vel ou Infarto Agudo do Mioc&#225;rdio [IAM]), h&#225; uma ampla varia&#231;&#227;o do risco para ocorr&#234;ncia de &#243;bito ou eventos isqu&#234;micos recorrentes<sup>2-7</sup>. Determinar o risco da ocorr&#234;ncia desses eventos adversos &#233; importante para definir o local ideal para realiza&#231;&#227;o dos cuidados m&#233;dicos, assim como ser&#227;o identificados os pacientes que possam se beneficiar de condutas mais potentes, dispendiosas e, muitas vezes, com maior risco<sup>2</sup>.</p>
    <p>Atualmente, para a estratifica&#231;&#227;o de risco nessa popula&#231;&#227;o, disp&#245;em-se de vari&#225;veis progn&#243;sticas independentes e de modelos de estratifica&#231;&#227;o de risco que s&#227;o recomendados pelas diretrizes nacionais e internacionais<sup>8-10</sup>.</p>
    <p>O escore de risco Dante Pazzanese<sup>11</sup> (escore DANTE) demonstrou na popula&#231;&#227;o de desenvolvimento boa habilidade (estat&#237;stica-C 0,74) para avaliar a probabilidade do evento composto de morte ou (re)infarto em at&#233; 30 dias, incorporando vari&#225;veis facilmente coletadas na pr&#225;tica m&#233;dica di&#225;ria: idade, antecedente de diabete melito ou acidente vascular encef&#225;lico, n&#227;o uso de inibidor da enzima conversora da angiotensina previamente &#224; interna&#231;&#227;o, depress&#227;o do segmento ST <underline>&gt;</underline> 0,5 mm no eletrocardiograma (ECG) da admiss&#227;o, eleva&#231;&#227;o da troponina card&#237;aca e eleva&#231;&#227;o da creatinina (<xref ref-type="fig" rid="aop_5378fig01">Figura 1</xref>). &#201; um modelo simples de estratifica&#231;&#227;o de risco, desenvolvido em uma popula&#231;&#227;o brasileira com SCA sem SST, de f&#225;cil execu&#231;&#227;o, com alto valor preditivo para eventos cardiovasculares.</p>
    <p content-type="asset">
      <fig id="aop_5378fig01">
        <graphic xlink:href="1678-4170-abc-101-03-0197-30163-gf01.jpg"/></fig>
    </p>
    <p>O objetivo desse estudo foi realizar a valida&#231;&#227;o externa do escore DANTE em pacientes com SCA sem SST.</p>
    <p>
      <bold>M&#233;todos</bold>
    </p>
    <p>
      <bold>Popula&#231;&#227;o em estudo</bold>
    </p>
    <p>Foi um estudo prospectivo com inclus&#227;o de pacientes consecutivos com SCA sem SST, admitidos no per&#237;odo de 8 de setembro de 2009 a 8 de outubro de 2010 no pronto-socorro de um centro terci&#225;rio em cardiologia. Pacientes foram eleg&#237;veis se apresentassem idade igual ou superior a 18 anos e sintomas consistentes com isquemia coronariana aguda dentro das &#250;ltimas 48 horas. Foram exclu&#237;dos aqueles com IAM com SST; sintomas de causas n&#227;o card&#237;acas; angina inst&#225;vel secund&#225;ria; e altera&#231;&#245;es confundidoras do eletrocardiograma (ECG [ritmo de marca-passo, ritmo de fibrila&#231;&#227;o atrial, bloqueios de ramo]). O Comit&#234; de &#201;tica em Pesquisa local aprovou o protocolo do estudo.</p>
    <p>
      <bold>Desfechos cl&#237;nicos</bold>
    </p>
    <p>Durante a interna&#231;&#227;o, os pacientes foram acompanhados por meio de visitas m&#233;dicas no pronto-socorro, na unidade coronariana ou na enfermaria e, posteriormente, ap&#243;s a alta hospitalar, por contato telef&#244;nico, para verifica&#231;&#227;o da presen&#231;a ou n&#227;o do evento composto de morte ou (re)infarto em at&#233; 30 dias.</p>
    <p>Dentro das primeiras 24 horas de admiss&#227;o, o paciente foi considerado apresentar o desfecho de (re)infarto, se ocorressem sintomas isqu&#234;micos com eleva&#231;&#227;o persistente do segmento ST maior que 0,1 mV em, pelo menos, duas deriva&#231;&#245;es cont&#237;guas, n&#227;o existentes na admiss&#227;o. Nesse per&#237;odo, a eleva&#231;&#227;o da CK-MB ou da troponina I card&#237;aca, sem eleva&#231;&#227;o do segmento ST, foi considerada relacionada ao evento da admiss&#227;o. Ap&#243;s 24 horas, o (re)infarto foi diagnosticado pela presen&#231;a de novas ondas Q ou novas eleva&#231;&#245;es da CK-MB, acima do limite da normalidade com ou sem altera&#231;&#227;o eletrocardiogr&#225;fica. Aos pacientes submetidos &#224; interven&#231;&#227;o coron&#225;ria percut&#226;nea (ICP) ou &#224; cirurgia de revasculariza&#231;&#227;o mioc&#225;rdica, a eleva&#231;&#227;o acima de tr&#234;s ou cinco vezes o limite da normalidade da CK-MB, ap&#243;s o procedimento, respectivamente<sup>12</sup>, foi necess&#225;ria para o diagn&#243;stico de infarto relacionado ao procedimento.</p>
    <p>
      <bold>C&#225;lculo do escore DANTE</bold>
    </p>
    <p>Caracter&#237;sticas basais, laboratoriais e eletrocardiogr&#225;ficas foram registradas na admiss&#227;o e durante a hospitaliza&#231;&#227;o. Para cada paciente foi calculado o escore DANTE de acordo com as vari&#225;veis progn&#243;sticas espec&#237;ficas do modelo original com suas respectivas pontua&#231;&#245;es. Em seguida, os pacientes foram agrupados em: muito baixo (at&#233; 5 pontos), baixo (6 a 10 pontos), intermedi&#225;rio (11 a 15 pontos) e alto risco (16 a 30 pontos).</p>
    <p>
      <bold>An&#225;lise estat&#237;stica</bold>
    </p>
    <p>As vari&#225;veis quantitativas foram descritas em m&#233;dias, percentis 25 (Per 25) e 75 (Per 75), medianas e Desvio Padr&#227;o (DP). Vari&#225;veis qualitativas foram expressas em frequ&#234;ncias absolutas ou porcentagens. O teste qui-quadrado de Pearson ou exato de Fisher foi utilizado para comparar vari&#225;veis qualitativas, e o teste n&#227;o param&#233;trico de Mann-Whitney para comparar vari&#225;veis quantitativas entre as popula&#231;&#245;es de desenvolvimento do modelo original<sup>11</sup> e de valida&#231;&#227;o.</p>
    <p>O escore DANTE foi analisado quanto &#224; sua capacidade discriminat&#243;ria determinando a &#225;rea sob a curva <italic>ROC</italic> (<italic>receiver operating characteristc</italic>)<sup>13</sup>, representada pela estat&#237;stica-C<sup>14</sup>.</p>
    <p>
      <bold>Resultados</bold>
    </p>
    <p>
      <bold>Caracter&#237;sticas basais</bold>
    </p>
    <p>Um total de 457 pacientes com SCA sem SST correspondeu &#224; popula&#231;&#227;o do estudo. Os dados da <xref ref-type="table" rid="aop_5378tab01">tabela 1</xref> trazem as caracter&#237;sticas basais da popula&#231;&#227;o estudada. Foram 169 pacientes (37%) com IAM sem SST e 288 (63%) com angina inst&#225;vel. A idade m&#233;dia foi de 62,1 anos (DP = 11,04) e 291 pacientes (63,7%) eram do sexo masculino. O fator de risco mais frequente foi hipertens&#227;o arterial sist&#234;mica (85,3%) seguido de dislipidemia (75,9%). Quase metade dos pacientes j&#225; havia sido submetida a algum tipo de procedimento de revasculariza&#231;&#227;o mioc&#225;rdica (49,5%).</p>
    <p content-type="asset">
      <table-wrap id="aop_5378tab01">
        <graphic xlink:href="1678-4170-abc-101-03-0197-30163-gt01.jpg"/></table-wrap>
    </p>
    <p>
      <bold>Tratamento e evolu&#231;&#227;o</bold>
    </p>
    <p>Semelhante &#224; popula&#231;&#227;o de desenvolvimento<sup>11</sup>, ospacientes na popula&#231;&#227;o de valida&#231;&#227;o foram amplamente medicados com betabloqueador (94,7%), &#225;cido acetilsalic&#237;lico (98,7%), antitromb&#237;nicos (96,3%), tienopirid&#237;nicos (96,3%), inibidor da enzima conversora da angiotensina (78,3%) e estatina (95,8%).</p>
    <p>A ICP foi indicada em 107 pacientes (23,4%) e a cirurgia de revasculariza&#231;&#227;o mioc&#225;rdica, em 51 (11,2%).</p>
    <p>Durante a interna&#231;&#227;o, 11 pacientes morreram (2,4%) e 5 (1,1%) apresentaram (re)infarto.</p>
    <p>O desfecho composto de morte ou (re)infarto em 30 dias ocorreu em 17 pacientes (3,7%), correspondendo ao evento do escore DANTE. Dos pacientes que apresentaram (re)infarto, dois foram relacionados &#224; ICP, dois &#224; cirurgia de revasculariza&#231;&#227;o mioc&#225;rdica, e um paciente, com tratamento cl&#237;nico.</p>
    <p>Nos dados da <xref ref-type="table" rid="aop_5378tab01">tabela 1</xref> apresentam-se as diferen&#231;as entre a popula&#231;&#227;o de desenvolvimento e de valida&#231;&#227;o.</p>
    <p>
      <bold>C&#225;lculo do escore de risco DANTE</bold>
    </p>
    <p>Para cada paciente foi calculada a pontua&#231;&#227;o do escore DANTE de acordo com a pontua&#231;&#227;o espec&#237;fica de cada vari&#225;vel do modelo original (<xref ref-type="fig" rid="aop_5378fig01">Figura 1</xref>). A distribui&#231;&#227;o das categorias de risco foi: muito baixo (38,9% [178 pacientes]), baixo (49,9% [228 pacientes]), intermedi&#225;rio (10,0% [46 pacientes]) ou alto risco (1,1% [5 pacientes]).</p>
    <p>Verificou-se um aumento progressivo na propor&#231;&#227;o do evento espec&#237;fico do escore DANTE com o aumento gradativo da pontua&#231;&#227;o: muito baixo risco (0,0%); baixo (3,9% [9 pacientes]); intermedi&#225;rio (10,9% [5 pacientes]); alto risco (60,0% [3 pacientes]) (<xref ref-type="fig" rid="aop_5378gra01">Gr&#225;fico 1</xref>). Da mesma forma, a m&#233;dia da pontua&#231;&#227;o do escore DANTE foi significativamente maior nos pacientes que apresentaram o evento: pacientes sem o evento do escore DANTE m&#233;dia 6,2 (2,9), mediana 6,0 (Per 25 = 4,0; Per 75 = 8,0); pacientes com o evento do escore DANTE m&#233;dia 11,5 (3,4), mediana 10,0 (Per 25 = 9,0; Per 75 = 15,0); p &lt; 0,0001 (<xref ref-type="fig" rid="aop_5378gra02">Gr&#225;fico 2</xref>).</p>
    <p content-type="asset">
      <fig id="aop_5378gra01">
        <graphic xlink:href="1678-4170-abc-101-03-0197-30163-gf02.jpg"/></fig>
    </p>
    <p content-type="asset">
      <fig id="aop_5378gra02">
        <graphic xlink:href="1678-4170-abc-101-03-0197-30163-gf03.jpg"/></fig>
    </p>
    <p>A estat&#237;stica-C (&#225;rea sob a curva <italic>ROC</italic>) demonstrou excelente habilidade preditiva do escore DANTE em discriminar quem apresentou ou n&#227;o o evento composto de morte ou (re)infarto em 30 dias: estat&#237;stica-C 0,87; intervalo de confian&#231;a 95% 0,81-0,94, p &lt; 0,0001 (<xref ref-type="fig" rid="aop_5378gra03">Gr&#225;fico 3</xref>).</p>
    <p content-type="asset">
      <fig id="aop_5378gra03">
        <graphic xlink:href="1678-4170-abc-101-03-0197-30163-gf04.jpg"/></fig>
    </p>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>At&#233; a d&#233;cada de 1990, a avalia&#231;&#227;o do risco para eventos adversos em SCA correspondia, quase exclusivamente, &#224; avalia&#231;&#227;o da presen&#231;a de disfun&#231;&#227;o ventricular esquerda ou de isquemia residual em um paciente com epis&#243;dio de IAM<sup>15</sup>. Em 1994, Braunwald e cols.<sup>4</sup>, pela primeira vez, idealizaram a estratifica&#231;&#227;o de risco em pacientes com SCA sem SST<sup>4,16</sup>. Em 2000, nas diretrizes norte-americanas, essa estrat&#233;gia passou a ser considerada uma recomenda&#231;&#227;o Classe I<sup>17</sup>, mantendo-se nas diretrizes de 2007<sup>10</sup>. Atualmente, &#233; parte integrante da conduta m&#233;dica j&#225; no primeiro contato m&#233;dico paciente no pronto-socorro.</p>
    <p>&#201; importante para a elabora&#231;&#227;o da triagem inicial no pronto-socorro, fato esse considerado, talvez, o principal papel dos servi&#231;os de emerg&#234;ncia, tanto para libera&#231;&#227;o de pacientes com maior seguran&#231;a, assim como para admiss&#227;o mais imediata daqueles de alto risco para a realiza&#231;&#227;o dos cuidados m&#233;dicos. O objetivo da estratifica&#231;&#227;o de risco &#233; determinar o progn&#243;stico de cada paciente, planejando o curso do tratamento, adicionando informa&#231;&#227;o ao paciente e aos seus familiares<sup>18</sup>. Deve ser iniciada na admiss&#227;o e atualizada durante a perman&#234;ncia do paciente no hospital, para que determinadas condutas m&#233;dicas sejam adotadas em curto prazo. A conduta m&#233;dica na interna&#231;&#227;o para incorpora&#231;&#227;o de medidas mais intensivas, como a administra&#231;&#227;o de medicamentos de maior risco ou a estrat&#233;gia invasiva precoce, deve basear-se na estratifica&#231;&#227;o de risco para ocorr&#234;ncia de eventos adversos. O principal foco, portanto, &#233; avaliar a probabilidade de ocorr&#234;ncia de eventos adversos, em especial, morte ou (re)infarto, de forma cada vez mais simples e objetiva, analisando dados da hist&#243;ria cl&#237;nica, do exame f&#237;sico, do ECG e os marcadores de necrose mioc&#225;rdica.</p>
    <p>Para as diretrizes do <italic>American College of Cardiology and American Heart Association Task Force</italic>, os modelos de estratifica&#231;&#227;o de risco s&#227;o considerados com grau de recomenda&#231;&#227;o Classe IIa<sup>10</sup>. Distintos modelos de estratifica&#231;&#227;o de risco foram desenvolvidos, utilizando-se de popula&#231;&#245;es de ensaios cl&#237;nicos randomizados<sup>2,19</sup> que n&#227;o foram selecionadas, primariamente, para a elabora&#231;&#227;o de um escore de risco. Com isso, a generaliza&#231;&#227;o desses modelos no mundo real poderia ser questionada. Al&#233;m disso, nos ensaios cl&#237;nicos, &#233; habitual a exclus&#227;o de pacientes sem altera&#231;&#245;es isqu&#234;micas ao ECG ou sem eleva&#231;&#227;o dos marcadores de necrose mioc&#225;rdica. Isso poderia originar um verdadeiro vi&#233;s de sele&#231;&#227;o, pois, de certa forma, a inclus&#227;o de determinadas altera&#231;&#245;es eletrocardiogr&#225;ficas, assim como os biomarcadores de necrose mioc&#225;rdica seriam "pressionados" a permanecerem no modelo final.</p>
    <p>Na escolha dos desfechos cl&#237;nicos analisados, a n&#227;o uniformidade &#233; considerada outro fato importante, visto que para alguns modelos a mortalidade por todas as causas foi analisada<sup>20,21</sup>, outros inclu&#237;ram morte ou (re)infarto<sup>19</sup>, ou associaram desfechos que n&#227;o apresentam const&#226;ncia na literatura em sua defini&#231;&#227;o e que s&#227;o influenciados pela pr&#225;tica m&#233;dica local, como revasculariza&#231;&#227;o mioc&#225;rdica urgente por isquemia recorrente<sup>2</sup>.</p>
    <p>No Brasil, para a realiza&#231;&#227;o da estratifica&#231;&#227;o de risco em pacientes com SCA sem SST, s&#227;o recomendados escores de risco desenvolvidos em popula&#231;&#245;es demograficamente diferentes da brasileira. Pela grande demanda em nosso pa&#237;s de pacientes que comp&#245;em essa s&#237;ndrome t&#227;o heterog&#234;nea, n&#227;o h&#225; justificativa para a n&#227;o incorpora&#231;&#227;o de um modelo desenvolvido em uma popula&#231;&#227;o tipicamente brasileira.</p>
    <p>Com os dados obtidos da hist&#243;ria cl&#237;nica, do exame f&#237;sico, do ECG e dos biomarcadores de necrose mioc&#225;rdica, rotineiramente coletados no departamento de emerg&#234;ncia, &#233; poss&#237;vel por meio do escore DANTE<sup>11</sup> a realiza&#231;&#227;o da estratifica&#231;&#227;o de risco com a aplica&#231;&#227;o de um modelo desenvolvido em uma popula&#231;&#227;o demograficamente semelhante &#224; popula&#231;&#227;o brasileira.</p>
    <p>O escore DANTE apresentou na popula&#231;&#227;o de desenvolvimento boa habilidade preditiva para os eventos adversos de morte ou (re)infarto em 30 dias, representada pela estat&#237;stica-C de 0,74<sup>11</sup>. Por&#233;m, na avalia&#231;&#227;o do desempenho do modelo, n&#227;o foi inclu&#237;da uma an&#225;lise em uma popula&#231;&#227;o independente. Portanto, por meio de nosso estudo apresentamos a primeira valida&#231;&#227;o externa do escore DANTE.</p>
    <p>Os pacientes dessa popula&#231;&#227;o de valida&#231;&#227;o, da mesma forma que na popula&#231;&#227;o de desenvolvimento, foram intensamente medicados com betabloqueador, &#225;cido acetilsalic&#237;lico, antitromb&#237;nicos, inibidor da enzima conversora da angiotensina e estatina. Por&#233;m, o uso de clopidogrel foi significativamente maior na popula&#231;&#227;o de valida&#231;&#227;o (p &lt; 0,0001) e, o de nitroglicerina, significativamente menor (p &lt; 0,0001).</p>
    <p>A realiza&#231;&#227;o de cinecoronariografia ocorreu sem diferen&#231;a significativa em compara&#231;&#227;o &#224; popula&#231;&#227;o de desenvolvimento (70,0% versus 71,5%; p = 0,553), apesar de a popula&#231;&#227;o do estudo ser de mais alto risco, demonstrado pela presen&#231;a de mais pacientes com fatores de risco para doen&#231;a arterial coronariana (hipertens&#227;o arterial sist&#234;mica ou dislipidemia) e maior ocorr&#234;ncia de doen&#231;a arterial coronariana <underline>&gt;</underline> 50% ou procedimentos de revasculariza&#231;&#227;o mioc&#225;rdica, pr&#233;vios &#224; interna&#231;&#227;o. Da mesma forma, maior n&#250;mero de pacientes apresentou eleva&#231;&#227;o dos marcadores de necrose mioc&#225;rdica (37,0% na popula&#231;&#227;o de valida&#231;&#227;o <italic>versus</italic> 29,6% na popula&#231;&#227;o de desenvolvimento; <italic>p </italic>= 0,005).</p>
    <p>A mortalidade hospitalar foi consideravelmente baixa (2,4%), corroborando com relatos anteriores<sup>22</sup>, n&#227;o ocorrendo diferen&#231;a com a popula&#231;&#227;o de desenvolvimento (p = 0,657). O desfecho combinado de morte ou (re)infarto em 30 dias (desfecho do escore DANTE) foi de 4,0% (popula&#231;&#227;o de valida&#231;&#227;o) versus 5,3% (popula&#231;&#227;o de desenvolvimento)<sup>11</sup>, sem diferen&#231;a significativa (p = 0,2).</p>
    <p>Com a pontua&#231;&#227;o definida para cada vari&#225;vel do escore DANTE em cada paciente e realizada a soma dos pontos, verificou-se aumento da propor&#231;&#227;o do risco de eventos adversos com o aumento gradativo da pontua&#231;&#227;o, realizando-se, portanto, uma valida&#231;&#227;o externa do escore DANTE. Por meio de um nomograma, observa-se a probabilidade de ocorr&#234;ncia do risco de morte ou (re)infarto em 30 dias.</p>
    <p>O escore DANTE apresentou excelente desempenho para avalia&#231;&#227;o progn&#243;stica nessa popula&#231;&#227;o independente, refletido pela estat&#237;stica-C de 0,87, justificando mais uma vez a sua aplicabilidade, mesmo em uma popula&#231;&#227;o de mais alto risco.</p>
    <p>Com a disponibilidade de um modelo em que se incluiu uma popula&#231;&#227;o brasileira, acredita-se em seu melhor papel para a avalia&#231;&#227;o progn&#243;stica em nosso meio. Deve-se, entretanto, como qualquer modelo de estratifica&#231;&#227;o de risco, ser reavaliado em longo prazo, para rean&#225;lise das vari&#225;veis j&#225; existentes, bem como para incorpora&#231;&#227;o de novas vari&#225;veis.</p>
    <p>
      <bold>Limita&#231;&#245;es</bold>
    </p>
    <p>Nesse estudo de valida&#231;&#227;o externa n&#227;o foi realizada a an&#225;lise em conjunto de modelos de estratifica&#231;&#227;o de risco recomendados pelas diretrizes atuais, como a estratifica&#231;&#227;o de risco de Braunwald<sup>16</sup>, escores de risco TIMI<sup>2</sup> e GRACE<sup>20,21</sup>. &#201; muito importante que seja elaborada em estudos futuros a valida&#231;&#227;o desses modelos e do escore DANTE em conjunto, especialmente avaliando banco de dados de registros brasileiros multic&#234;ntricos<sup>23</sup>.</p>
    <p>
      <bold>Conclus&#227;o</bold>
    </p>
    <p>O escore DANTE apresentou excelente habilidade preditiva para a ocorr&#234;ncia de &#243;bito ou (re)infarto em 30 dias em popula&#231;&#227;o independente da popula&#231;&#227;o de desenvolvimento, e pode ser incorporado na avalia&#231;&#227;o progn&#243;stica de pacientes com SCA sem SST.</p>
    <p>
      <bold>Contribui&#231;&#227;o dos autores</bold>
    </p>
    <p>Concep&#231;&#227;o e desenho da pesquisa e Reda&#231;&#227;o do manuscrito: Santos ES; Obten&#231;&#227;o de dados: Santos ES, Minuzzo L; An&#225;lise e interpreta&#231;&#227;o dos dados: Santos ES, Minuzzo L, Souza R, Timerman A; An&#225;lise estat&#237;stica: Santos ES, Souza R; Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual: Santos ES, Minuzzo L, Timerman A.</p>
    <p>
      <bold>Potencial Conflito de Interesses</bold>
    </p>
    <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
    <p>
      <bold>Fontes de Financiamento</bold>
    </p>
    <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
    <p>
      <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
    </p>
    <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
    <p>
      <fn id="enda" fn-type="corresp">
        <label>
          <bold>Correspond&#234;ncia:</bold>
        </label>
        <p> Elizabete Silva dos Santos </p>
        <p> Avenida Dr. Dante Pazzanese, n&#250;mero 500 </p>
        <p> CEP 04012-909 &#150; Vila Mariana &#150; S&#227;o Paulo, SP, Brasil </p>
        <p> E-mail: </p>
        <p><email xlink:href="elizabetessantos@cardiol.br">elizabetessantos@cardiol.br</email>; </p>
        <p>
          <email xlink:href="elizabetessantos@bol.com.br">elizabetessantos@bol.com.br</email>
        </p>
      </fn>
    </p>
    <p>Artigo recebido em 13/01/13; revisado em 11/05/13; aceito em 14/05/13.</p>
  </body>
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  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Prospective validation of the dante pazzanese risk score in non-ST-segment elevation acute coronary syndrome</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>BACKGROUND: In non-ST-segment elevation acute coronary syndrome (ACS), the likelihood of adverse events should be estimated. Guidelines recommend risk stratification models for that purpose. The Dante Pazzanese risk score (DANTE score) is a simple risk stratification model composed with the following variables: age increase (0 to 9 points); history of diabetes mellitus (2 points) or stroke (4 points); no use of angiotensin-converting-enzyme inhibitor (1 point); creatinine elevation (0 to 10 points); combination of troponin elevation and ST-segment depression (0 to 4 points). OBJECTIVE: To validate the DANTE score in patients with non-ST-segment elevation ACS. METHODS: Prospective, observational study including 457 patients, from September 2009 to October 2010. The patients were grouped in risk categories according to the original model score as follows: very low; low; intermediate; and high. The predictive ability of the score was assessed by using C-statistics. RESULTS: The sample comprised 291 (63.7%) men, the mean age being 62.1 years (SD=11.04). The event death or (re)infarction in 30 days was observed in 17 patients (3.7%). Progressive increase in the proportion of events was observed as the score increased: very low risk = 0.0%; low risk = 3.9%; intermediate risk = 10.9%; high risk = 60.0%; p &lt; 0.0001. C-statistics was 0.87 (95% CI: 0.81-0.94; p &lt; 0.0001). CONCLUSION: DANTE score showed an excellent capacity to predict the specific events, and can be incorporated to the prognostic assessment of patients with non-ST-segment elevation ACS.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Acute Coronary Syndrome</kwd>
        <kwd>Validation Studies</kwd>
        <kwd>Propensity Score</kwd>
        <kwd>Risk</kwd>
        <kwd>Probability</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <fn id="end-body2">
          <label>
            <bold>Prospective validation of the dante pazzanese risk score in non-ST-segment elevation acute coronary syndrome</bold>
          </label>
          <p>
            <bold>Elizabete Silva dos Santos; Luiz Minuzzo; Roberta de Souza; Ari Timerman</bold>
          </p>
        </fn>
      </p>
      <p>Instituto Dante Pazzanese de Cardiologia, S&#227;o Paulo, SP - Brazil</p>
      <p>Mailing Address</p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p><bold>BACKGROUND:</bold> In non-ST-segment elevation acute coronary syndrome (ACS), the likelihood of adverse events should be estimated. Guidelines recommend risk stratification models for that purpose. The Dante Pazzanese risk score (DANTE score) is a simple risk stratification model composed with the following variables: age increase (0 to 9 points); history of diabetes mellitus (2 points) or stroke (4 points); no use of angiotensin-converting-enzyme inhibitor (1 point); creatinine elevation (0 to 10 points); combination of troponin elevation and ST-segment depression (0 to 4 points).</p>
      <p><bold>OBJECTIVE:</bold> To validate the DANTE score in patients with non-ST-segment elevation ACS.</p>
      <p><bold>METHODS: </bold>Prospective, observational study including 457 patients, from September 2009 to October 2010. The patients were grouped in risk categories according to the original model score as follows: very low; low; intermediate; and high. The predictive ability of the score was assessed by using C-statistics.</p>
      <p><bold>RESULTS:</bold> The sample comprised 291 (63.7%) men, the mean age being 62.1 years (SD=11.04). The event death or (re)infarction in 30 days was observed in 17 patients (3.7%). Progressive increase in the proportion of events was observed as the score increased: very low risk = 0.0%; low risk = 3.9%; intermediate risk = 10.9%; high risk = 60.0%; p &lt; 0.0001. C-statistics was 0.87 (95% CI: 0.81-0.94; p &lt; 0.0001).</p>
      <p><bold>CONCLUSION:</bold> DANTE score showed an excellent capacity to predict the specific events, and can be incorporated to the prognostic assessment of patients with non-ST-segment elevation ACS.</p>
      <p><bold>Keywords:</bold> Acute Coronary Syndrome / diagnosis; Validation Studies; Propensity Score; Risk; Probability. </p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p>Cardiovascular diseases are an important cause of death worldwide. They usually represent the main cause of death not only in developed but also in developing countries<sup>1</sup>. Because of the heterogeneous nature of patients with non-ST-segment elevation acute coronary syndrome (ACS), such as unstable angina or acute myocardial infarction (AMI), the risk of death or recurrent ischemic events varies<sup>2-7</sup>. Determining the risk of those adverse events is important to define the ideal place for medical care provision, and to identify patients who might benefit from a more effective, expensive and often risky management<sup>2</sup>.</p>
      <p>Currently, the risk stratification for that population involves independent prognostic variables and risk stratification models recommended by national and international guidelines<sup>8-10</sup>.</p>
      <p>The Dante Pazzanese score for risk stratification<sup>11</sup> (DANTE score) has shown a good ability (C-statistics, 0.74) to assess the likelihood of the composite endpoint of death or (re)infarction in up to 30 days in the population it was developed, incorporating the following variables easily collected in daily medical practice: age; history of diabetes mellitus or stroke; no use of angiotensin-converting-enzyme inhibitor prior to hospitalization; ST-segment depression <underline>&gt;</underline> 0.5 mm on electrocardiogram at admission; cardiac troponin level elevation; and creatinine level elevation (<xref ref-type="fig" rid="en_aop_5378fig01-body2">Figure 1</xref>). It is a simple risk stratification model developed in a Brazilian population with non-ST-segment elevation ACS, which is easily performed and has a high predictive value for cardiovascular events. </p>
      <p content-type="asset">
        <fig id="en_aop_5378fig01-body2">
          <graphic xlink:href="1678-4170-abc-101-03-0197-30163-gf01-en.jpg"/></fig>
      </p>
      <p>This study aimed to perform the external validation of the DANTE risk score in patients with non-ST-segment elevation ACS. </p>
      <p>
        <bold>Methods</bold>
      </p>
      <p>
        <bold>Study population</bold>
      </p>
      <p>This was a prospective study with consecutive inclusion of patients with non-ST-segment elevation ACS, admitted to the emergency unit of a cardiology tertiary center from September 8<sup>th</sup>, 2009, to October 8<sup>th</sup>, 2010. Patients aged at least 18 years and with symptoms consistent with acute coronary ischemia within the last 48 hours were eligible for this study. Patients with the following characteristics were excluded: ST-segment elevation AMI; noncardiac symptoms; secondary unstable angina; and confounding electrocardiographic (EKG) changes, such as pacemaker rhythm, atrial fibrillation rhythm, and bundle-branch blocks. The local Committee on Ethics and Research approved the study protocol.</p>
      <p>
        <bold>Clinical outcomes</bold>
      </p>
      <p>During hospitalization, the patients were followed up with medical visits at the emergency unit, the coronary unit or at the ward, and later, after hospital discharge, through telephone contact, to assess the incidence of death or (re)infarction in up to 30 days. </p>
      <p>Within the first 24 hours after admission, patients were considered to experience the outcome of (re)infarction if they had ischemic symptoms with persistent ST-segment elevation greater than 0.1 mV on at least two contiguous leads, which were not present on admission. During that period, the elevation of CK-MB or cardiac troponin I levels with no ST-segment elevation was considered to be related to the event of admission. After 24 hours, (re)infarction was diagnosed by the presence of new Q waves or new CK-MB level elevation above the normal limit with or without EKG changes. Patients undergoing percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery required a CK-MB level elevation greater than three or five times the normal limit, respectively, after the procedure<sup>12</sup> to be diagnosed with procedure-related infarction.</p>
      <p>
        <bold>DANTE score calculation</bold>
      </p>
      <p>Basal, laboratory and EKG characteristics were recorded on hospital admission and during hospitalization. DANTE score was calculated for each patient according to the specific prognostic variables of the original model, being the risk categories as follows: very low (up to 5 points); low (6 to 10 points); intermediate (11 to 15 points); and high (16 to 30 points).</p>
      <p>
        <bold>Statistical analysis</bold>
      </p>
      <p>The quantitative variables were presented as means, percentiles (25<sup>th</sup> percentile and 75<sup>th</sup> percentile), medians and standard deviations (SD). Qualitative variables were expressed as absolute frequencies or percentages. Pearson chi-square test or Fisher exact test was used to compare qualitative variables, and the non-parametric Mann-Whitney test to compare quantitative variables between the original model<sup>11</sup> and validation populations. </p>
      <p>The DANTE score discriminatory capacity was analyzed by determining the area under the receiver operating characteristic curve (ROC)<sup>13</sup>, represented by C-statistics<sup>14</sup>.</p>
      <p>
        <bold>Results</bold>
      </p>
      <p>
        <bold>Baseline characteristics</bold>
      </p>
      <p>This study population consisted of 457 patients with non-ST-segment elevation ACS, of whom, 169 (37%) had non-ST-segment elevation AMI and 288 (63%) had unstable angina. Their mean age was 62.1 years (SD = 11.04), and 291 (63.7%) were of the male sex. The most frequent risk factor was systemic arterial hypertension (85.3%), followed by dyslipidemia (75.9%). Almost half of the patients (49.5%) had already undergone a myocardial revascularization procedure. <xref ref-type="table" rid="en_aop_5378tab01-body2">Table 1</xref> shows the baseline characteristics of the population studied.</p>
      <p content-type="asset">
        <table-wrap id="en_aop_5378tab01-body2">
          <graphic xlink:href="1678-4170-abc-101-03-0197-30163-gt01-en.jpg"/></table-wrap>
      </p>
      <p>
        <bold>Treatment and outcome</bold>
      </p>
      <p>Similarly to the population of the original model development<sup>11</sup>, patients in the validation population were treated with beta-blockers (94.7%), acetylsalicylic acid (98.7%), thrombin inhibitors (96.3%), thienopyridine derivatives (96.3%), angiotensin-converting-enzyme inhibitors (78.3%), and statin (95.8%).</p>
      <p>Percutaneous coronary intervention was indicated to 107 patients (23.4%), and coronary artery bypass graft surgery, to 51 (11.2%). </p>
      <p>During hospitalization, 11 patients died (2.4%) and 5 (1.1%) had (re)infarction. </p>
      <p>The composite endpoint of death or (re)infarction in 30 days was observed in 17 patients (3.7%), corresponding to the DANTE score event. The (re)infarctions observed were related to the following: PCI in two; coronary artery bypass graft surgery in two; and clinical treatment in one.</p>
      <p><xref ref-type="table" rid="en_aop_5378tab01-body2">Table 1</xref> shows the differences between the original model and validation populations.</p>
      <p>
        <bold>DANTE risk score calculation</bold>
      </p>
      <p>The DANTE risk score was calculated for each patient according to the specific score of each variable of the original model (<xref ref-type="fig" rid="en_aop_5378fig01-body2">Figure 1</xref>). The distribution of the risk categories was as follows: very low (178 patients, 38.9%); low (228 patients, 49.9%); intermediate (46 patients, 10.0%); and high (5 patients, 1.1%). </p>
      <p>A progressive increase in the proportion of the DANTE score specific event was observed with the gradual increase in scoring as follows: very low risk, 0.0%; low, 3.9% (9 patients); intermediate, 10.9% (5 patients); high risk, 60.0% (3 patients) (<xref ref-type="undefined" rid="en_aop_5378cha01-body2">Char 1</xref>). Similarly, the mean final DANTE score was significantly higher in patients having the event, as follows: for patients without the event, the mean DANTE score was 6.2 (SD=2.9), and the median, 6.0 (25<sup>th</sup> percentile = 4.0; 75<sup>th</sup> percentile = 8.0); for patients with the event, the mean DANTE score was 11.5 (SD=3.4), and the median, 10.0 (25<sup>th</sup> percentile = 9.0; 75<sup>th</sup> percentile = 15.0); p &lt; 0.0001 (<xref ref-type="undefined" rid="en_aop_5378cha02-body2">Char 2</xref>).</p>
      <p content-type="asset">
        <undefined id="en_aop_5378cha01-body2">
          <inline-graphic xlink:href="https://minio.scielo.br/documentstore/1678-4170/tp4hwMzTn7ghTMr6RHBX5Fc/1929ae960b52eb37c618368cfaf2e73d05666808.jpg"/>
        </undefined>
      </p>
      <p content-type="asset">
        <undefined id="en_aop_5378cha02-body2">
          <inline-graphic xlink:href="https://minio.scielo.br/documentstore/1678-4170/tp4hwMzTn7ghTMr6RHBX5Fc/311a351289492063ec306a67580b2828c5ad5aab.jpg"/>
        </undefined>
      </p>
      <p>C-statistics (area under the ROC curve) evidenced the excellent predictive ability of the DANTE score to discriminate those with or without the compound event of death or (re)infarction in 30 days: C-statistics, 0.87; 95% confidence interval: 0.81-0.94, p &lt; 0.0001 (<xref ref-type="fig" rid="en_aop_5378cha03-body2">Chart 3</xref>).</p>
      <p content-type="asset">
        <fig id="en_aop_5378cha03-body2">
          <graphic xlink:href="1678-4170-abc-101-03-0197-30163-gf02-en.jpg"/></fig>
      </p>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>Up to the 1990s, assessing the risk of adverse events in ACS meant almost exclusively assessing the presence of left ventricular dysfunction or residual ischemia in patients with an episode of AMI<sup>15</sup>. In 1994, Braunwald et al<sup>4</sup>, for the first time, considered risk stratification for patients with non-ST-segment elevation ACS<sup>4,16</sup>. In 2000, in the North American guidelines, that strategy began to be considered a level I recommendation<sup>17</sup>, being maintained in the 2007 guidelines<sup>10</sup>. Currently, risk stratification is part of medical management already on the first physician-patient contact at the emergency unit.</p>
      <p>Risk stratification is important to the initial screening at the emergency unit, this being considered the major role of emergency services, for both the safer discharge of patients and prompter admission of those at high risk for medical management. Its objective is to determine the prognosis of each patient, planning the course of treatment and providing information to patients and their families<sup>18</sup>. It should be initiated on admission and updated during hospitalization, so that certain medical managements could be adopted in the short run. On admission, the adoption of more intensive measures, such as an aggressive medical treatment or an early invasive strategy, should be based on risk stratification for the occurrence of adverse events. Thus, the focus is to assess the likelihood of adverse events, especially death or (re)infarction, in an increasingly simple and objective manner, analyzing the clinical history, physical exam, EKG, and myocardial necrosis markers. </p>
      <p>In the report of the American College of Cardiology and American Heart Association Task Force on practice guidelines, the models of risk stratification are considered as level IIa recommendation<sup>10</sup>. Different risk stratification models have been developed by using randomized clinical trial populations<sup>2,19</sup> that were not primarily selected for the elaboration of a risk score. Thus, the generalization of those models in real world could be questioned. In addition, in clinical trials, the exclusion of patients without ischemic changes on EKG or without an elevation in myocardial necrosis markers is usual. This could originate a true selection bias, because the inclusion of certain EKG changes, as well as of myocardial necrosis markers, would be "pressed" to remain in the final model. </p>
      <p>When choosing the clinical outcomes analyzed, heterogeneity is considered another important fact; while in some models, all-cause mortality was assessed<sup>20,21</sup>, others included death or (re)infarction<sup>19</sup>, or associated outcomes whose definition in literature showed no consistency and that are influenced by local medical practices, such as urgent myocardial revascularization due to recurring ischemia<sup>2</sup>. </p>
      <p>In Brazil, the risk stratification of patients with non-ST-segment elevation ACS is based on risk scores developed in populations demographically different from the Brazilian one. Because of the large number of patients with that heterogeneous syndrome in Brazil, the development of a model in a typically Brazilian population is recommended.</p>
      <p>With data obtained from clinical history, physical exam, EKG and myocardial necrosis markers, routinely collected at the emergency unit, the DANTE score<sup>11</sup> provides risk stratification by applying a model developed in a population demographically similar to the Brazilian one. </p>
      <p>In the population in which the original model of the DANTE score was developed, it showed to be a good predictor of the adverse events of death or (re)infarction in 30 days, represented by a C-statistics of 0.74<sup>11</sup>. However, when assessing model performance, its analysis in an independent population was not included. Thus, our study provides the first external validation of the DANTE score. </p>
      <p>The patients of the validation population, similarly to those of the population of the original model development, were intensely medicated with beta-blockers, acetylsalicylic acid, thrombin inhibitors, angiotensin-converting-enzyme inhibitors, and statin. However, the use of clopidogrel was significantly higher in the validation population (p &lt; 0.0001), while that of nitroglycerin was significantly lower (p &lt; 0.0001). </p>
      <p>Performing coronary angiography did not significantly differ as compared with the population of the original model development (70.0% versus 71.5%; p = 0.553), although the study population had a higher risk, evidenced by a larger number of patients with risk factors for coronary artery disease (systemic arterial hypertension or dyslipidemia) and greater occurrence of coronary artery disease <underline>&gt;</underline> 50% or myocardial revascularization procedures prior to hospitalization. Similarly, a larger number of patients showed an elevation in myocardial necrosis markers (37.0% in the validation population versus 29.6% in the population of the original model development; p = 0.005). </p>
      <p>In-hospital mortality was considerably low (2.4%), confirming previous reports<sup>22</sup>, and did not differ from that of the population of the original model development (p = 0.657). The combined outcome of death or (re)infarction in 30 days (outcome of the DANTE score) was 4.0% for the validation population versus 5.3% for the population of the original model development<sup>11</sup>, no significant difference (p = 0.2). </p>
      <p>With a summed score for the variables of the DANTE score for each patient, an increase in the risk of adverse events was observed with the gradual increase in the final score, representing, thus, the external validation of the DANTE score. By use of a nomogram, the likelihood of the occurrence of death or (re)infarction in 30 days is obtained. </p>
      <p>The DANTE score showed an excellent performance to assess the prognosis of that independent population, reflected in the C-statistics of 0.87, justifying once more its applicability, even in a population at higher risk.</p>
      <p>A model including a Brazilian population in its elaboration is believed to play a better role in the prognostic assessment of that population. However, as any model of risk stratification, it should be reassessed in the long run to analyze the existing variables and to incorporate new ones.</p>
      <p>
        <bold>Limitations</bold>
      </p>
      <p>In this study of external validation, the joint analysis of risk stratification models recommended by current guidelines, such as Braunwald's risk stratification<sup>16</sup>, TIMI<sup>2</sup> and GRACE<sup>20,21</sup> risk scores, was not performed. It is worth noting that future studies should perform the joint validation of those models and the DANTE score, especially assessing the database of multicenter Brazilian registries<sup>23</sup>.</p>
      <p>
        <bold>Conclusion</bold>
      </p>
      <p>The DANTE risk score showed to be an excellent predictor of the occurrence of death or (re)infarction in 30 days, regardless of the population of the original model development, and can be incorporated in the prognostic assessment of patients with non-ST-segment elevation ACS.</p>
      <p>
        <bold>Author Contributions: </bold>
      </p>
      <p>Conception and design of the research: Santos ES; Analysis and interpretation of the data: Santos ES, Minuzzo L, Souza R, Timerman A; Acquisition of data: Santos ES, Minuzzo L; Statistical analysis: Santos ES, Souza R; Writing of the manuscript: Santos ES; Critical revision of the manuscript for intellectual content: Santos ES, Minuzzo L, Timerman A.</p>
      <p>
        <bold>Potential Conflict of Interest</bold>
      </p>
      <p>No potential conflict of interest relevant to this article was reported.</p>
      <p>
        <bold>Sources of Funding</bold>
      </p>
      <p>There were no external funding sources for this study.</p>
      <p>
        <bold>Study Association</bold>
      </p>
      <p>This study is not associated with any post-graduation program.</p>
      <p>
        <bold>References</bold>
      </p>
    </body>
  </sub-article>
</article>
