<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.1 20151215//EN" "https://jats.nlm.nih.gov/publishing/1.1/JATS-journalpublishing1.dtd">
<article xmlns:xlink="http://www.w3.org/1999/xlink" specific-use="sps-1.9" dtd-version="1.1" xml:lang="pt" article-type="research-article">
  <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">PCz4C8qYRQbxtSpy4VKscKL</article-id>
      <article-id pub-id-type="other">00012</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2006001500012</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(06)08700212</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2006001500012</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Progn&#243;stico do duke-escore versus cintilografia em pacientes com fatores de risco para doen&#231;a arterial coronariana: seguimento de um ano</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Gasperin</surname>
            <given-names>Carlos Alberto</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Bueno</surname>
            <given-names>Caroline Pereira</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Yamada</surname>
            <given-names>Airton Seiji</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rocha</surname>
            <given-names>Gilberto Alves da</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Heinze</surname>
            <given-names>Regina C&#233;lia Portugal Freixo</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nunes</surname>
            <given-names>D&#233;bora Cristina Fontoura de Mello</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Trevisan</surname>
            <given-names>Isabelle Vianna</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mostiack</surname>
            <given-names>Deisi Raquel</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Xavie</surname>
            <given-names>L&#226;nia Romanzin</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Silva</surname>
            <given-names>Cl&#225;udia Maria Castelo Branco</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="city">Curitiba</named-content>
          <named-content content-type="state">PR</named-content>
        </addr-line>
        <institution content-type="orgname">Centro de Radioimunoensaio e Medicina Nuclear do Paran&#225;</institution>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>08</month>
        <year>2006</year>
      </pub-date>
      <volume>87</volume>
      <issue>2</issue>
      <fpage>146</fpage>
      <lpage>152</lpage>
      <history>
        <date date-type="received">
          <day>11</day>
          <month>10</month>
          <year>2005</year>
        </date>
        <date date-type="accepted">
          <day>24</day>
          <month>03</month>
          <year>2006</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>OBJETIVO: Determinar a sensibilidade, a especificidade e o risco de eventos cardiovasculares em pacientes com Duke-escore (DE) baixo, intermedi&#225;rio e alto risco, em compara&#231;&#227;o com a presen&#231;a (ou n&#227;o) de defeitos de perfus&#227;o &#224; cintilografia do mioc&#225;rdio. M&#201;TODOS: Estudo prospectivo, consecutivo, com 173 pacientes com 2 ou mais fatores de risco para doen&#231;a arterial coronariana (DAC), que foram submetidos &#224; cintilografia de perfus&#227;o do mioc&#225;rdio com tetrofosmin marcado com tecn&#233;cio-Tc 99m (CPM) e ao teste ergom&#233;trico (aplicando-se o DE), de um bairro de Curitiba, entre janeiro de 2003 a fevereiro de 2004. Os pacientes tiveram seguimento de 13&#177;1 meses e 162 completaram o acompanhamento. Foi avaliada a presen&#231;a de morte, angina, infarto agudo do mioc&#225;rdio, angioplastia coronariana e revasculariza&#231;&#227;o do mioc&#225;rdio. RESULTADOS: A m&#233;dia do DE dos pacientes que apresentaram eventos (18) foi de -0,27 (95% IC= -3,97 a +3,91) e daqueles livres de eventos (144) foi de +4,92 (95% IC= +4,03 a +5,81), com p&lt;0,00069. A sensibilidade do DE foi de 72,22% e da CPM foi de 77,78%, sem diferen&#231;a estat&#237;stica, com p=0,21. A especificidade do DE foi de 54,17% e a da CPM foi de 88,19%, com p&lt;0,0001. A curva de Kaplan-Meier demonstrou que 94% dos pacientes com DE baixo risco permaneceram livres de eventos em 01 ano. Em contraste, todos os de alto risco apresentaram eventos no mesmo per&#237;odo. Os que apresentaram DE de intermedi&#225;rio risco apresentaram 15% de eventos em 01 ano. CONCLUS&#195;O: O DE foi t&#227;o sens&#237;vel quanto CPM em determinar o risco para DAC em um ano. Os pacientes com DE &lt;-0,27 tiveram maior risco de eventos card&#237;acos.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Exerc&#237;cio</kwd>
        <kwd>teste</kwd>
        <kwd>progn&#243;stico</kwd>
        <kwd>doen&#231;a arterial coronariana</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>28</day>
        <month>09</month>
        <year>2006</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>ARTIGO ORIGINAL</bold>
    </p>
    <p>Progn&#243;stico do duke-escore versus cintilografia em pacientes com fatores de risco para doen&#231;a arterial coronariana. Seguimento de um ano</p>
    <p>
      <bold>Carlos Alberto Gasperin; Caroline Pereira Bueno; Airton Seiji Yamada; Gilberto Alves da Rocha; Regina C&#233;lia Portugal Freixo Heinze; D&#233;bora Cristina Fontoura de Mello Nunes; Isabelle Vianna Trevisan; Deisi Raquel Mostiack; L&#226;nia Romanzin Xavier; Cl&#225;udia Maria Castelo Branco Silva</bold>
    </p>
    <p>Centro de Radioimunoensaio e Medicina Nuclear do Paran&#225; &#150; CERMEN - Curitiba, PR</p>
    <p>
      <xref ref-type="corresp" rid="end">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>OBJETIVO: </bold>Determinar a sensibilidade, a especificidade e o risco de eventos cardiovasculares em pacientes com Duke-escore (DE) baixo, intermedi&#225;rio e alto risco, em compara&#231;&#227;o com a presen&#231;a (ou n&#227;o) de defeitos de perfus&#227;o &#224; cintilografia do mioc&#225;rdio. </p>
    <p><bold>M&#201;TODOS: </bold>Estudo prospectivo, consecutivo, com 173 pacientes com 2 ou mais fatores de risco para doen&#231;a arterial coronariana (DAC), que foram submetidos &#224; cintilografia de perfus&#227;o do mioc&#225;rdio com tetrofosmin marcado com tecn&#233;cio-Tc <sup>99m </sup>(CPM) e ao teste ergom&#233;trico (aplicando-se o DE), de um bairro de Curitiba, entre janeiro de 2003 a fevereiro de 2004. Os pacientes tiveram seguimento de 13&#177;1 meses e 162 completaram o acompanhamento. Foi avaliada a presen&#231;a de morte, angina, infarto agudo do mioc&#225;rdio, angioplastia coronariana e revasculariza&#231;&#227;o do mioc&#225;rdio. </p>
    <p><bold>RESULTADOS: </bold>A m&#233;dia do DE dos pacientes que apresentaram eventos (18) foi de -0,27 (95% IC= -3,97 a +3,91) e daqueles livres de eventos (144) foi de +4,92 (95% IC= +4,03 a +5,81), com p&lt;0,00069. A sensibilidade do DE foi de 72,22% e da CPM foi de 77,78%, sem diferen&#231;a estat&#237;stica, com p=0,21. A especificidade do DE foi de 54,17% e a da CPM foi de 88,19%, com p&lt;0,0001. A curva de Kaplan-Meier demonstrou que 94% dos pacientes com DE baixo risco permaneceram livres de eventos em 01 ano. Em contraste, todos os de alto risco apresentaram eventos no mesmo per&#237;odo. Os que apresentaram DE de intermedi&#225;rio risco apresentaram 15% de eventos em 01 ano. </p>
    <p><bold>CONCLUS&#195;O: </bold>O DE foi t&#227;o sens&#237;vel quanto CPM em determinar o risco para DAC em um ano. Os pacientes com DE &lt;-0,27 tiveram maior risco de eventos card&#237;acos.</p>
    <p><bold>Palavras-chave:</bold> Exerc&#237;cio, teste, progn&#243;stico, doen&#231;a arterial coronariana.</p>
    <p>Apesar dos avan&#231;os tecnol&#243;gicos do teste ergom&#233;trico (TE), como filtros computadorizados que permitem um tra&#231;ado com pouca interfer&#234;ncia e dos in&#250;meros conhecimentos metodol&#243;gicos adquiridos nos seus mais de sessenta anos de exist&#234;ncia, este exame apresenta menor sensibilidade diagn&#243;stica na detec&#231;&#227;o da doen&#231;a arterial coronariana (DAC) do que a de outros m&#233;todos de estresse, como a cintilografia de perfus&#227;o do mioc&#225;rdio, o ecocardiograma de estresse e a tomografia computadorizada do cora&#231;&#227;o<sup>1</sup>. Recentemente, foram desenvolvidos &#237;ndices progn&#243;sticos, como os &#237;ndices de "Duke - escore"<sup>2</sup> e o "Veterans &#150; escore"<sup>3</sup> aplicados ao TE com o objetivo de aumentar sua sensibilidade diagn&#243;stica e progn&#243;stica.</p>
    <p>Nosso objetivo neste estudo foi o de comparar a sensibilidade e a especificidade do &#237;ndice progn&#243;stico do Duke-escore (DE) com a cintilografia de perfus&#227;o do mioc&#225;rdio (Tc <sup>99m </sup>-tetrofosmin) de estresse f&#237;sico (CPM) num mesmo grupo de pacientes com fatores de risco para DAC, durante 12 meses.</p>
    <p>
      <bold>M&#201;TODOS</bold>
    </p>
    <p>Foram alocados para o estudo 311 pacientes de forma consecutiva, encaminhados para exame de cintilografia do mioc&#225;rdio, de um determinado bairro (Semin&#225;rio) de Curitiba, Paran&#225;, com dois ou mais fatores de risco para DAC, de janeiro de 2003 at&#233; fevereiro de 2004. Os fatores de risco considerados foram: hipertens&#227;o arterial sist&#234;mica, diabete melito, dislipidemia, obesidade, doen&#231;a arterial coronariana pr&#233;via, tabagismo e hist&#243;ria familiar para coronariopatia. Todos os indiv&#237;duos foram informados quanto ao estudo e assinaram termo de consentimento. Foram considerados dentro do grupo com evento coronariano, os indiv&#237;duos que apresentaram, ao longo de 12 meses, interna&#231;&#227;o hospitalar por <italic>angina pectoris</italic>, infarto agudo do mioc&#225;rdio (IAM), angioplastia coronariana e revasculariza&#231;&#227;o do mioc&#225;rdio, al&#233;m de morte por IAM. Os demais foram considerados indiv&#237;duos sem evento coronariano.</p>
    <p>Dos 311 indiv&#237;duos, 138 foram encaminhados para exame farmacol&#243;gico (por: dificuldade de deambula&#231;&#227;o, bloqueio de ramo esquerdo, taquiarritmias ventriculares graves, fibrila&#231;&#227;o atrial ou portadores de marcapasso) e, em seguida, exclu&#237;dos do estudo. Os demais 173 pacientes que realizaram teste ergom&#233;trico (protocolo de Bruce) e cintilografia de perfus&#227;o do mioc&#225;rdio com tetrosfosmin marcado com tecn&#233;cio (Tc <sup>99m</sup>), ambos no mesmo dia, foram inclu&#237;dos no estudo. Desses, n&#227;o foi poss&#237;vel obter o seguimento em 11 pacientes, os quais foram exclu&#237;dos do estudo.</p>
    <p>Os 162 pacientes restantes foram acompanhados de forma prospectiva, durante no m&#237;nimo 12 meses, para o objetivo de avaliar a presen&#231;a dos seguintes eventos coronarianos: <italic>angina pectoris</italic>, infarto agudo do mioc&#225;rdio, necessidade de angioplastia transluminal coronariana percut&#226;nea ou revasculariza&#231;&#227;o do mioc&#225;rdio e morte. </p>
    <p>O protocolo de esteira de Bruce foi aplicado a todos os indiv&#237;duos que realizaram a ergometria. O &#237;ndice de Duke escore<sup>2</sup> do teste ergom&#233;trico foi obtido com a f&#243;rmula: tempo (minutos) &#150; 5 X (infradesn&#237;vel de segmento ST mm) &#150; 4 X (dor tor&#225;cica: 0= sem dor/ 1= dor n&#227;o limitante/ 2= dor limitante). Foi considerado Duke escore baixo risco o &#237;ndice <underline>&gt;</underline>+5, risco intermedi&#225;rio entre +4 a -10 e alto risco <underline>&lt;</underline> -11. A an&#225;lise de segmento ST foi obtida, sem o conhecimento dos dados cl&#237;nicos do paciente, por 2 examinadores com experi&#234;ncia em ergometria e os resultados confrontados entre si, com a finalidade de se diminu&#237;rem erros subjetivos de an&#225;lise. O tempo foi obtido pelo sistema computadorizado utilizado para realizar o teste ergom&#233;trico (Ergo-S/Dixtal). A an&#225;lise de dor foi obtida por meio de question&#225;rio respondido pelo paciente durante o teste ergom&#233;trico, como descrito. </p>
    <p>A cintilografia de perfus&#227;o do mioc&#225;rdio com tetrofosmin marcado com tecn&#233;cio (Tc <sup>99m</sup>) foi obtida com protocolo de um dia. Inicialmente foi feita a imagem de repouso e, cerca de 6 horas depois, foi repetida a imagem ap&#243;s estresse f&#237;sico em esteira ergom&#233;trica. Foram obtidas imagens tomogr&#225;ficas de 60 quadros com aquisi&#231;&#227;o cont&#237;nua no repouso. As imagens tomogr&#225;ficas ap&#243;s estresse f&#237;sico foram sincronizadas ao eletrocardiograma do paciente, sendo o intervalo RR dividido em 8 quadros, totalizando 480 quadros por exame. Foi considerada como anormal a CPM que apresentou qualquer defeito de perfus&#227;o transit&#243;ria de parede de ventr&#237;culo esquerdo (isquemia), qualquer defeito de perfus&#227;o persistente de parede de ventr&#237;culo esquerdo em paciente sem hist&#243;ria pr&#233;via de IAM ou com qualquer hipocinesia associada ou n&#227;o &#224; fra&#231;&#227;o de eje&#231;&#227;o &lt; 50% &#224; an&#225;lise funcional, sem hist&#243;ria pr&#233;via de IAM. </p>
    <p>Foram determinadas as m&#233;dias com desvio-padr&#227;o e erro-padr&#227;o entre os grupos com e sem eventos coronarianos para ambos os m&#233;todos (DE e CPM), utilizando-se o m&#233;todo "<italic>t</italic> &#150; student" para duas vari&#225;veis independentes. Para an&#225;lise entre as vari&#225;veis de risco coronariano, foi utilizado o "teste de Fischer". Foram, ainda, determinadas a sensibilidade e especificidade progn&#243;sticas do DE e da CPM, comparadas entre si, aplicando-se o "teste entre duas propor&#231;&#245;es independentes". Por fim, foi determinada a curva livre de eventos coronarianos, pelo "m&#233;todo de sobreviv&#234;ncia de Kaplan-Meier". Foi considerado como estatisticamente significativo o &#237;ndice de p&lt;0,05. </p>
    <p>
      <bold>RESULTADOS</bold>
    </p>
    <p>Os pacientes que apresentaram evento coronariano ao longo de 12 meses foram 18 e os que permaneceram livres de eventos totalizaram 144.</p>
    <p>A <xref ref-type="table" rid="tab01">tabela 1</xref> mostra que o sexo masculino, a hipertens&#227;o arterial, o diabete melito e m&#233;dia maior de idade foram estatisticamente mais freq&#252;entes no grupo com evento coronariano. Na <xref ref-type="table" rid="tab02">tabela 2</xref> demonstrou-se que n&#227;o houve diferen&#231;a estatisticamente significativa entre as propor&#231;&#245;es dos fatores de risco pesquisados entre as popula&#231;&#245;es com DE baixo risco e intermedi&#225;rio/alto risco. No caso da cintilografia, na <xref ref-type="table" rid="tab03">tabela 3</xref> registrou-se que ocorreu maior porcentagem de casos do sexo masculino, maior n&#250;mero de hipertensos, diab&#233;ticos e com coronariopatia pr&#233;via no grupo com cintilografia alterada. </p>
    <table-wrap id="tab01">
      <graphic xlink:href="1678-4170-abc-87-02-0146-00012-gt01.jpg"/></table-wrap>
    <table-wrap id="tab02">
      <graphic xlink:href="1678-4170-abc-87-02-0146-00012-gt02.jpg"/></table-wrap>
    <table-wrap id="tab03">
      <graphic xlink:href="1678-4170-abc-87-02-0146-00012-gt03.jpg"/></table-wrap>
    <p>O n&#250;mero de pacientes com DE baixo, intermedi&#225;rio e alto, bem como o n&#250;mero de pacientes com CPM normal e alterada est&#227;o representados nas <xref ref-type="fig" rid="fig01">figuras 1</xref> e <xref ref-type="fig" rid="fig02">2</xref>, respectivamente.</p>
    <fig id="fig01">
      <graphic xlink:href="1678-4170-abc-87-02-0146-00012-gf01.jpg"/></fig>
    <fig id="fig02">
      <graphic xlink:href="1678-4170-abc-87-02-0146-00012-gf02.jpg"/></fig>
    <p>A m&#233;dia do DE obtida em pacientes livres de eventos coronarianos foi de +4,92 (IC95%: +4,03 a +5,81). A m&#233;dia do DE obtida no grupo de pacientes que apresentaram eventos coronarianos foi de &#150;0,27 (IC95%: -3,97 a +3,91). Como se demonstra na <xref ref-type="fig" rid="fig03">figura 3</xref>, ocorreu diferen&#231;a estatisticamente significativa entre a m&#233;dia do DE entre os dois grupos, com p&lt; 0,00069. Nesta figura, tamb&#233;m se demonstram o erro-padr&#227;o e o desvio-padr&#227;o.</p>
    <fig id="fig03">
      <graphic xlink:href="1678-4170-abc-87-02-0146-00012-gf03.jpg"/></fig>
    <p>A sensibilidade do DE foi de 72,22% e da CPM foi de 77,78%, por&#233;m, apesar da sensibilidade maior da CPM, n&#227;o ocorreu significa&#231;&#227;o estat&#237;stica em rela&#231;&#227;o ao DE, com p= 0,21. </p>
    <p>A especificidade do DE foi de 54,17% e da CPM foi de 88,19%. A alta especificidade da CPM em rela&#231;&#227;o ao DE apresentou relev&#226;ncia estat&#237;stica, com p&lt;00001.</p>
    <p>A m&#233;dia da fra&#231;&#227;o de eje&#231;&#227;o obtida pela an&#225;lise funcional da CPM foi de 60,65% nos pacientes livres de eventos em 12 meses e de 55,58% nos que apresentaram evento no mesmo per&#237;odo; n&#227;o houve relev&#226;ncia estat&#237;stica entre os dois grupos, com p=0,08.</p>
    <p>Na an&#225;lise proporcional acumulada livre de eventos ao longo de 12 meses (curvas de Kaplan-Meier), observou-se n&#237;tida diferen&#231;a entre os pacientes com CPM normal e CPM alterada (p&lt;0,0001), conforme se demonstra na <xref ref-type="fig" rid="fig04">figura 4</xref>. Acima de 95% dos pacientes com CPM normal ficaram livres de eventos neste per&#237;odo, contra apenas 55% dos pacientes com CPM anormal. A mesma an&#225;lise para o DE, demonstrou que ao longo de 12 meses, cerca de 94% dos pacientes considerados de baixo risco ficaram livres de eventos, ao passo que todos os considerados alto risco tiveram eventos coronarianos (p&lt;0,0001). Cerca de 15% dos pacientes de risco intermedi&#225;rio apresentaram eventos no decorrer de 12 meses.</p>
    <fig id="fig04">
      <graphic xlink:href="1678-4170-abc-87-02-0146-00012-gf04.jpg"/></fig>
    <p>
      <bold>DISCUSS&#195;O</bold>
    </p>
    <p>Balady e cols.<sup>4</sup> demonstraram em mais de 3.000 pacientes assintom&#225;ticos com fatores de risco para doen&#231;a arterial coronariana, acompanhados num per&#237;odo superior a 18 anos, que o teste de esfor&#231;o p&#244;de auxiliar a detectar pessoas com maior risco de eventos, tanto em pacientes que apresentavam escore de Framingham de alto risco, quanto os de risco baixo. Tr&#234;s vari&#225;veis obtidas no teste ergom&#233;trico foram importantes: a depress&#227;o de segmento ST &gt;1mm, a capacidade de exerc&#237;cio em METs e a incapacidade de atingir a freq&#252;&#234;ncia card&#237;aca subm&#225;xima prevista. Para cada MET acrescido ao desempenho no esfor&#231;o, ocorreu uma redu&#231;&#227;o de 13% do risco de eventos. Vale notar que o infradesnivelamento de segmento ST e o n&#250;mero de METs atingido no esfor&#231;o, dois dos dados mais significativos que, isoladamante, acrescentaram informa&#231;&#245;es sobre o risco ao escore de Framingham, s&#227;o tamb&#233;m aplicados para obter o DE. O estudo acima demonstrou, de forma indireta e em grande popula&#231;&#227;o, o que o DE procura avaliar com o teste ergom&#233;trico de forma simples e expressa de forma num&#233;rica: o risco de evento coronariano do paciente. At&#233; o momento, em nenhum estudo se comparou o progn&#243;stico do DE com a CPM na popula&#231;&#227;o brasileira, o que motivou a realiza&#231;&#227;o deste estudo.</p>
    <p>O dado mais importante dele foi a sensibilidade do DE, apesar de ter sido menor que a da CPM, e n&#227;o ter apresentado diferen&#231;a estat&#237;stica significativa. Numa meta-an&#225;lise descrita por Frohelicher e cols.<sup>1</sup> j&#225; se havia demonstrado que o DE elevou a acur&#225;cia do teste ergom&#233;trico para n&#237;vel semelhante ao da CPM com T&#225;lio, por&#233;m n&#227;o maior do que a CPM com Tecn&#233;cio. Outro fator que poderia explicar essa similaridade estat&#237;stica entre esses m&#233;todos &#233; o de que a an&#225;lise deste estudo se limitou a 12 meses, quando a maioria dos estudos do DE e CPM foram superiores a 3 anos. Uma placa ateroscler&#243;tica, mesmo vulner&#225;vel, nem sempre traz evento cl&#237;nico num per&#237;odo de 12 meses, podendo instabilizar-se num per&#237;odo superior a este, dependendo do controle dos fatores de risco. Por&#233;m os m&#233;todos de estresse j&#225; poderiam detectar precocemente altera&#231;&#245;es como, por exemplo, no caso da CPM, de uma perfus&#227;o mioc&#225;rdica deficit&#225;ria. Ainda, propositadamente, foram escolhidos pacientes com dois ou mais fatores de risco para doen&#231;a arterial coronariana, uma popula&#231;&#227;o mais suscet&#237;vel a eventos e provavelmente com maior n&#250;mero de coron&#225;rias envolvidas. Sabidamente, o teste ergom&#233;trico apresenta maior sensibilidade em pacientes multiarteriais, o que poderia ter elevado a sensibilidade do DE. Por&#233;m o mesmo ocorre com a CPM e com qualquer outro m&#233;todo de estresse<sup>5</sup>. Por &#250;ltimo, uma sensibilidade menor da CPM poderia ter sido causada pelo fato de que o paciente que consegue deambular e completar o teste ergom&#233;trico, possui melhor progn&#243;stico do que os pacientes submetidos a teste farmacol&#243;gico. O estudo GISSI-2 demonstrou em grupo de pacientes infartados, tratados com trombol&#237;ticos, que aqueles que n&#227;o conseguiram deambular em esteira tiveram progn&#243;stico pior do que os que completaram pelo menos o segundo est&#225;gio de Bruce<sup>6</sup>. Por isso n&#227;o se analisou a sensibilidade da CPM na totalidade, mas somente dos pacientes que conseguiram fazer esteira, ou seja, os de melhor progn&#243;stico.</p>
    <p> A especificidade do DE, por&#233;m, foi muito baixa em rela&#231;&#227;o &#224; CPM, com signific&#226;ncia estat&#237;stica. Esse fato torna-se dif&#237;cil de explicar, uma vez que Gianrossi e cols.<sup>7</sup> demonstraram numa meta-an&#225;lise uma especificidade maior que a sensibilidade do teste ergom&#233;trico. Um dado que chamou a aten&#231;&#227;o no nosso estudo foi o de que boa parte dos pacientes livres de eventos tiveram DE de risco intermedi&#225;rio, &#224; custa de infradesnivelamento de segmento ST. Um estudo desenvolvido por Bugiardini e cols.<sup>8</sup> demonstrou em 42 mulheres, seguidas ao longo de 10 anos, todas com teste ergom&#233;trico alterado associado a defeitos de perfus&#227;o &#224; CPM, por&#233;m com cateterismo normal, um alto risco de desenvolver doen&#231;a arterial coronariana (les&#227;o evidente em novo cateterismo), infarto agudo do mioc&#225;rdio e morte. Assim, demonstrou-se que a altera&#231;&#227;o no teste ergom&#233;trico antecedeu em anos a les&#227;o coronariana ateroscler&#243;tica. Apesar de este estudo ter tido um n&#250;mero de casos pequenos, lan&#231;ou uma luz no entendimento do porqu&#234; encontrarmos tantos exames rotulados como "falsos-positivos" no teste ergom&#233;trico. Provavelmente a altera&#231;&#227;o de segmento ST, nesses casos, indicou que esses pacientes apresentem disfun&#231;&#227;o endotelial importante e com maior risco de eventos futuros. </p>
    <p>Somente 3 pacientes apresentaram DE alto risco (todos os 3 desenvolveram evento em um ano). Por esse motivo, foram analisados com os do grupo intermedi&#225;rio. Atualmente, est&#227;o sendo desenvolvidos alguns estudos, em que se analisa se o valor do DE limite entre o grupo de pacientes intermedi&#225;rio para alto risco n&#227;o estaria subvalorizado. Isto &#233;, para que o paciente atinja o valor de alto risco (inferior a "-11"), este ter&#225; de apresentar altera&#231;&#245;es muito importantes de segmento ST e, geralmente, presen&#231;a de angina de peito durante o teste ergom&#233;trico. Esses estudos indicar&#227;o, no futuro, qual seria o valor exato que deveremos considerar para o DE alto risco. Talvez um "valor de corte" bem maior que este (mais pr&#243;ximo de zero), j&#225; que indica alto risco. Em nosso estudo, por exemplo, demonstramos , como visto na <xref ref-type="fig" rid="fig03">figura 3</xref>, que os pacientes de maior risco, que apresentaram evento ao longo de 12 meses, foram os que apresentaram DE inferior a zero (&lt;00), com alto significado estat&#237;stico. Outro ponto importante para corroborar esse fato foi o de que em nosso estudo mostramos um n&#250;mero relativamente grande de eventos nos pacientes com DE de risco intermedi&#225;rio.</p>
    <p>A curva de Kaplan-Meier (<xref ref-type="fig" rid="fig05">fig. 5</xref>) deixa clara a diferen&#231;a entre os escores de risco do DE com rela&#231;&#227;o ao per&#237;odo livre de eventos, principalmente entre o DE alto risco para o baixo risco, demonstrando a confiabilidade desse m&#233;todo em predizer risco de eventos. Apesar dessa confiabilidade, o DE possui limita&#231;&#245;es. Pacientes com infradesnivelamento de segmento ST j&#225; no tra&#231;ado pr&#233;-teste, com idade superior a 75 anos, e em diab&#233;ticos, o DE demonstrou ter menor sensibilidade diagn&#243;stica<sup>9</sup>. Nesses casos, a associa&#231;&#227;o com outros m&#233;todos de estresse pode beneficiar o paciente.</p>
    <fig id="fig05">
      <graphic xlink:href="1678-4170-abc-87-02-0146-00012-gf05.jpg"/></fig>
    <p>Na <xref ref-type="fig" rid="fig04">figura 4</xref> registrou-se que os indiv&#237;duos com CPM normal tiveram menos de 5% de eventos no per&#237;odo deste estudo. Muitos destes apresentaram DE de risco intermedi&#225;rio. De fato, a CPM pode determinar quais dos pacientes, que apresentaram DE de risco intermedi&#225;rio, t&#234;m maior probabilidade de eventos coronarianos. Conforme citam Beller e cols.<sup>10</sup>, pacientes com DE intermedi&#225;rio que apresentaram CPM normal tiveram uma mortalidade inferior a 0,4% ao ano, enquanto entre os que apresentaram CPM alterada, a mortalidade foi de 8,9% ao ano. A CPM teve grande import&#226;ncia na detec&#231;&#227;o dos indiv&#237;duos de maior risco, em conformidade com in&#250;meros estudos pr&#233;vios<sup>11-13</sup>. </p>
    <p>A principal limita&#231;&#227;o do nosso estudo foi o n&#250;mero relativamente pequeno de casos. Um estudo com maior n&#250;mero de casos poderia n&#227;o s&#243; comprovar o nosso achado de forma mais eficaz, como tamb&#233;m determinar os dados obtidos para v&#225;rios subgrupos de pacientes. Por exemplo, poder&#237;amos separ&#225;-los de acordo com os fatores de risco e determinar o DE de maior risco para cada um deles. Outra limita&#231;&#227;o, j&#225; mencionada, foi a an&#225;lise do grupo de pacientes encaminhados &#224; CPM, que conseguiram realizar a ergometria, ou seja, de melhor progn&#243;stico. Isto pode ter interferido na an&#225;lise comparativa entre os dois m&#233;todos de estresse. Por fim, outra limita&#231;&#227;o que vale lembrar deste estudo foi a an&#225;lise subjetiva do examinador, tanto para determina&#231;&#227;o do segmento ST na ergometria, quanto da imagem da CPM. Para minimizar quaisquer erros, foram obtidos os dados por mais de um examinador e, principalmente, sem que a an&#225;lise da ergometria tivesse conhecimento do resultado da CPM e vice-versa. </p>
    <p>Concluindo o nosso estudo, o DE demonstrou ser t&#227;o sens&#237;vel quanto a CPM na detec&#231;&#227;o de pacientes com maior risco de evento coronariano em 12 meses, principalmente os indiv&#237;duos que apresentaram DE inferior a zero, mesmo sendo assintom&#225;ticos. Muitos desses pacientes, classificados como de risco intermedi&#225;rio, devem receber aten&#231;&#227;o especial do cl&#237;nico. Sugere-se que sejam encaminhados para investiga&#231;&#227;o com outros m&#233;todos de estresse, como a CPM, para confirma&#231;&#227;o diagn&#243;stica. Os que apresentaram DE de alto risco devem ser investigados imediatamente e, at&#233; mesmo, encaminhados para cineangiocoronariografia.</p>
    <p>
      <bold>Agradecimentos </bold>
    </p>
    <p>Aos t&#233;cnicos de radiologia Avanildo Rubert, Patr&#237;cia Marina Piffar, Adair Obreg&#227;o de Lima, Jo&#227;o Maria da Silva, Roberto Ferreira da Silva, Leoni Matzenbacher, Sandro Afonso e &#224;s secret&#225;rias S&#237;lvia Paula Cola&#231;o e Jocilene Raspzak Gorri &#224; dedica&#231;&#227;o aos pacientes deste estudo e respeito com eles. </p>
    <p>
      <bold>Potencial Conflito de Interesses</bold>
    </p>
    <p>Declaro n&#227;o haver conflitos de interesses pertinentes.</p>
    <p>
      <fn id="end" fn-type="corresp">
        <label>
          <bold>Correspond&#234;ncia:</bold>
        </label>
        <p> Carlos Alberto Gasperin </p>
        <p> Rua Gon&#231;alves Dias, 655 </p>
        <p> 80240-340 &#150; Curitiba, PR </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="acgasperin@cendicor.com.br">acgasperin@cendicor.com.br</email>
        </p>
      </fn>
    </p>
    <p> Recebido em 11/10/05 </p>
    <p> Aceito em 24/03/06</p>
  </body>
  <back>
    <ref-list>
      <ref id="B1">
        <mixed-citation>1. Froelicher VF, Fearon WF, Fergusson CM,    et al. Lessons learned from studies of the standard exercise ecg test. Chest.    1999; 116:1442-51.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Lessons learned from studies of the standard exercise ecg test</article-title>
          <source>Chest.</source>
          <date>
            <year>1999</year>
          </date>
          <fpage>1442</fpage>
          <lpage>51</lpage>
          <volume>116</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Froelicher</surname>
              <given-names>VF</given-names>
            </name>
            <name>
              <surname>Fearon</surname>
              <given-names>WF</given-names>
            </name>
            <name>
              <surname>Fergusson</surname>
              <given-names>CM</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B2">
        <mixed-citation>2. Mark DB, Shaw L, Harrel FE, et al. Prognostic    value of a treadmill exercise score in outpatients with suspected coronary artery    disease. N Engl J Med. 1991;325:849-53.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Prognostic value of a treadmill exercise score in outpatients with suspected coronary artery disease</article-title>
          <source>N Engl J Med.</source>
          <date>
            <year>1991</year>
          </date>
          <fpage>849</fpage>
          <lpage>53</lpage>
          <volume>325</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Mark</surname>
              <given-names>DB</given-names>
            </name>
            <name>
              <surname>Shaw</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Harrel</surname>
              <given-names>FE</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B3">
        <mixed-citation>3. Morrow K, Morris CK, Froehlicher VF, et    al. Prediction of cardiovascular death in men undergoing noninvasive evaluation    for coronary artery disease. Ann Intern Med. 1993;118:689-95.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Prediction of cardiovascular death in men undergoing noninvasive evaluation for coronary artery disease</article-title>
          <source>Ann Intern Med.</source>
          <date>
            <year>1993</year>
          </date>
          <fpage>689</fpage>
          <lpage>95</lpage>
          <volume>118</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Morrow</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Morris</surname>
              <given-names>CK</given-names>
            </name>
            <name>
              <surname>Froehlicher</surname>
              <given-names>VF</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B4">
        <mixed-citation>4<bold>. </bold>Balady GK, Larson MG, Vasan RS,    et al. Usefulness of exercise testing in the prediction of coronary disease    risk among asymptomatic persons as a function of the Framingham Risk Score.    Circulation. 2004;110:1920-5.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Usefulness of exercise testing in the prediction of coronary disease risk among asymptomatic persons as a function of the Framingham Risk Score</article-title>
          <source>Circulation</source>
          <date>
            <year>2004</year>
          </date>
          <fpage>1920</fpage>
          <lpage>5</lpage>
          <volume>110</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Balady</surname>
              <given-names>GK</given-names>
            </name>
            <name>
              <surname>Larson</surname>
              <given-names>MG</given-names>
            </name>
            <name>
              <surname>Vasan</surname>
              <given-names>RS</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B5">
        <mixed-citation>5. Tavel ME. Stress testing in cardiac evaluation.    Current concepts with emphasis on the ECG. Chest. 2001;119:907-25. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Stress testing in cardiac evaluation: Current concepts with emphasis on the ECG</article-title>
          <source>Chest</source>
          <date>
            <year>2001</year>
          </date>
          <fpage>907</fpage>
          <lpage>25</lpage>
          <volume>119</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Tavel</surname>
              <given-names>ME</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B6">
        <mixed-citation>6. Volpi A, de Vita C, Franzoni MG, et al<italic>.</italic>    Predictors of nonfatal reinfarction in survivors of myocardial infarction after    thrombolysis: results of the Gruppo italiano per lo studio della sopravvivenza    nell infarto miocardico (GISSI-2) data base. J Am Coll Cardiol. 1994;24:608-15.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Predictors of nonfatal reinfarction in survivors of myocardial infarction after thrombolysis: results of the Gruppo italiano per lo studio della sopravvivenza nell&#8217; infarto miocardico (GISSI-2) data base</article-title>
          <source>J Am Coll Cardiol</source>
          <date>
            <year>1994</year>
          </date>
          <fpage>608</fpage>
          <lpage>15</lpage>
          <volume>24</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Volpi</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>de Vita</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Franzoni</surname>
              <given-names>MG</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B7">
        <mixed-citation>7. Gianrossi R, Detrano R, Mulvihill D, et    al. Exercise-induced ST depression in the diagnosis of coronary artery disease.    A meta-analysis. Circulation. 1989; 80:87-98.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Exercise-induced ST depression in the diagnosis of coronary artery disease: A meta-analysis</article-title>
          <source>Circulation</source>
          <date>
            <year>1989</year>
          </date>
          <fpage>87</fpage>
          <lpage>98</lpage>
          <volume>80</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Gianrossi</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Detrano</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Mulvihill</surname>
              <given-names>D</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B8">
        <mixed-citation>8. Bugiardini R, Manfrini O, Pizzi C, Fontana    F, Morgagni G. Endothelial function predicts future development of coronary    artery disease. A study of women with chest pain and normal coronary angiograms.    Circulation. 2004;109:2518-23.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Endothelial function predicts future development of coronary artery disease: A study of women with chest pain and normal coronary angiograms</article-title>
          <source>Circulation</source>
          <date>
            <year>2004</year>
          </date>
          <fpage>2518</fpage>
          <lpage>23</lpage>
          <volume>109</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Bugiardini</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Manfrini</surname>
              <given-names>O</given-names>
            </name>
            <name>
              <surname>Pizzi</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Fontana</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Morgagni</surname>
              <given-names>G</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B9">
        <mixed-citation>9. Kwok JM, Miller TD, Hodge DO, Gibbons RJ.    Prognostic value of the Duke treadmill score in the elderly. J Am Coll Cardiol.    2002;39:1475-81.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Prognostic value of the Duke treadmill score in the elderly</article-title>
          <source>J Am Coll Cardiol</source>
          <date>
            <year>2002</year>
          </date>
          <fpage>1475</fpage>
          <lpage>81</lpage>
          <volume>39</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Kwok</surname>
              <given-names>JM</given-names>
            </name>
            <name>
              <surname>Miller</surname>
              <given-names>TD</given-names>
            </name>
            <name>
              <surname>Hodge</surname>
              <given-names>DO</given-names>
            </name>
            <name>
              <surname>Gibbons</surname>
              <given-names>RJ</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B10">
        <mixed-citation>10. Beller GA, Zaret BL. Contribution of nuclear    cardiology to diagnosis and prognosis of patients with coronary artery disease.    Circulation. 2000; 101:1465-78.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Contribution of nuclear cardiology to diagnosis and prognosis of patients with coronary artery disease</article-title>
          <source>Circulation</source>
          <date>
            <year>2000</year>
          </date>
          <fpage>1465</fpage>
          <lpage>78</lpage>
          <volume>101</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Beller</surname>
              <given-names>GA</given-names>
            </name>
            <name>
              <surname>Zaret</surname>
              <given-names>BL</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B11">
        <mixed-citation>11. Shaw LJ, Peterson ED, Shaw LK, et al<italic>.</italic>    Use of a prognostic treadmill score in identifying diagnostic coronary disease    subgroups. Circulation. 1998;98:1622-30.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Use of a prognostic treadmill score in identifying diagnostic coronary disease subgroups</article-title>
          <source>Circulation</source>
          <date>
            <year>1998</year>
          </date>
          <fpage>1622</fpage>
          <lpage>30</lpage>
          <volume>98</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Shaw</surname>
              <given-names>LJ</given-names>
            </name>
            <name>
              <surname>Peterson</surname>
              <given-names>ED</given-names>
            </name>
            <name>
              <surname>Shaw</surname>
              <given-names>LK</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B12">
        <mixed-citation>12. Lauer MS, Lytle B, Pashkow F, Snader CE,    Marwick TH. Prediction of death and myocardial infarction by screening with    exercise-thallium testing after coronary-artery-bypass grafting. Lancet. 1998;351:61522.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Prediction of death and myocardial infarction by screening with exercise-thallium testing after coronary-artery-bypass grafting</article-title>
          <source>Lancet.</source>
          <date>
            <year>1998</year>
          </date>
          <fpage>615</fpage>
          <lpage>22</lpage>
          <volume>351</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Lauer</surname>
              <given-names>MS</given-names>
            </name>
            <name>
              <surname>Lytle</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Pashkow</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Snader</surname>
              <given-names>CE</given-names>
            </name>
            <name>
              <surname>Marwick</surname>
              <given-names>TH</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B13">
        <mixed-citation>13. Parisi AF, Hartingan PM, Folland ED. Evaluation    of exercise thallium scintigraphy versus exercise electrocardiography in predicting    survival outcomes and morbid cardiac events in patients with single- and double-vessel    disease. Findings from the angioplasty compared to medicine (ACME) study. J    Am Coll Cardiol. 1997;30:125663.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Evaluation of exercise thallium scintigraphy versus exercise electrocardiography in predicting survival outcomes and morbid cardiac events in patients with single- and double-vessel disease: Findings from the angioplasty compared to medicine (ACME) study</article-title>
          <source>J Am Coll Cardiol</source>
          <date>
            <year>1997</year>
          </date>
          <fpage>1256</fpage>
          <lpage>63</lpage>
          <volume>30</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Parisi</surname>
              <given-names>AF</given-names>
            </name>
            <name>
              <surname>Hartingan</surname>
              <given-names>PM</given-names>
            </name>
            <name>
              <surname>Folland</surname>
              <given-names>ED</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
    </ref-list>
  </back>
  <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">Prognosis of duke treadmill score versus scintilography in patients at risk for coronary artery disease: one year follow-up</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>OBJECTIVE: The purpose was to determine the sensitivity, the specificity and a year-long risk of subsequent cardiovascular events in patients with low, intermediate and high risk prognostic Duke treadmill score (DTS) in comparison with the presence (or not) of the myocardial perfusion defects on radionuclide images. METHODS: A prospective study, with 173 consecutive patients with 02 or more risk factors to coronary artery disease (CAD), who underwent to exercise single photon - emission computed tomographic myocardial perfusion images using technetium-99m tetrophosmin (SPECT) and treadmill test (with DTS), from one neighbourhood of Curitiba city, between January 2003 and February 2004, were followed up for cardiac-cause mortality and major cardiac events. Follow-up was performed in 13&#177; 1 months and in 162 patients was complete. RESULTS: The DTS mean those patients with cardiac event (18) over a year was -0.27 (95% CI= -3.97 to +3.91) and those free cardiac event patients (144) was +4.92 (95% CI= +4.03 to +5.81), with p&lt;0.00069. The DTS sensitivity was 72.22% and the SPECT sensitivity was 77.78%, with no significant difference p=0.21. The DTS specificity was 54.17% and the SPECT specificity was 88.19%, with p&lt;0.0001. The cumulative proportion free-events (Kaplan-Meier) curves demonstrated that 94% those patients with low-risk DTS remained free-cardiac events. In contrast, all high-risk DTS had adverse cardiac events. Those patients with intermediate-risk DTS had 15% of cardiac event over a year. CONCLUSIONS: The DTS was as sensitivity as SPECT in determine a year risk for CAD. Those patients with DTS &lt;-0.27 had high-risk cardiac event.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Exercise</kwd>
        <kwd>tests</kwd>
        <kwd>prognosis</kwd>
        <kwd>coronary artery disease</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ORIGINAL ARTICLE</bold>
      </p>
      <p>Prognosis of Duke treadmill score versus scintilography in patients at risk for coronary artery disease. One year follow-up </p>
      <p>
        <bold>Carlos Alberto Gasperin; Caroline Pereira Bueno; Airton Seiji Yamada; Gilberto Alves da Rocha; Regina C&#233;lia Portugal Freixo Heinze; D&#233;bora Cristina Fontoura de Mello Nunes; Isabelle Vianna Trevisan; Deisi Raquel Mostiack; L&#226;nia Romanzin Xavier; Cl&#225;udia Maria Castelo Branco Silva</bold>
      </p>
      <p>Centro de Radioimunoensaio e Medicina Nuclear do Paran&#225; &#150; CERMEN - Curitiba, PR - Brazil</p>
      <p>
        <xref ref-type="corresp" rid="end-body2">Mailing Address</xref>
      </p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p><bold>OBJECTIVE:</bold> The purpose was to determine the sensitivity, the specificity and a year-long risk of subsequent cardiovascular events in patients with low, intermediate and high risk prognostic Duke treadmill score (DTS) in comparison with the presence (or not) of the myocardial perfusion defects on radionuclide images.</p>
      <p><bold>METHODS:</bold> A prospective study, with 173 consecutive patients with 02 or more risk factors to coronary artery disease (CAD), who underwent to exercise single photon &#150; emission computed tomographic myocardial perfusion images using technetium-99m tetrophosmin (SPECT) and treadmill test (with DTS), from one neighbourhood of Curitiba city, between January 2003 and February 2004, were followed up for cardiac-cause mortality and major cardiac events. Follow-up was performed in 13&#177; 1 months and in 162 patients was complete.</p>
      <p><bold>RESULTS:</bold> The DTS mean those patients with cardiac event (18) over a year was -0.27 (95% CI= -3.97 to +3.91) and those free cardiac event patients (144) was +4.92 (95% CI= +4.03 to +5.81), with p&lt;0.00069. The DTS sensitivity was 72.22% and the SPECT sensitivity was 77.78%, with no significant difference p=0.21. The DTS specificity was 54.17% and the SPECT specificity was 88.19%, with p&lt;0.0001. The cumulative proportion free-events (Kaplan-Meier) curves demonstrated that 94% those patients with low-risk DTS remained free-cardiac events. In contrast, all high-risk DTS had adverse cardiac events. Those patients with intermediate-risk DTS had 15% of cardiac event over a year.</p>
      <p><bold>CONCLUSION:</bold> The DTS was as sensitivity as SPECT in determine a year risk for CAD. Those patients with DTS &lt;-0,27 had high-risk cardiac event.</p>
      <p><bold>Key words:</bold> Exercise, tests, prognosis, coronary artery disease</p>
      <p>Despite technological advances of exercise stress testing (EST), such as the addition of filters that yield tracing with little interference, and different methodological approaches acquired during its over sixty years of existence, this exam is less sensitive for detecting coronary artery disease (CAD) than other stress tests, such as myocardium perfusion scintigraphy, stress echocardiogram and myocardial computed tomography<sup>1</sup>. Recently, several prognostic indices were developed, such as the "Duke Score"<sup>2</sup> and the "Veterans Score"<sup>3</sup>, that are applied to exercise stress testing to enhance diagnostic and prognostic sensitivity.</p>
      <p>The objective of this study was to compare sensitivity and specificity between the Duke Score prognostic index and stress myocardium perfusion scintigraphy (Tc<sup>99m</sup>-tetrofosmin) in a group of patients with risk factors of CAD, over a 12-month period.</p>
      <p>
        <bold>METHODS</bold>
      </p>
      <p>Three hundred and eleven consecutive patients, with two or more risk factors for CAD, participated in this study. They were referred from a neighborhood (Semin&#225;rio) in Curitiba to undergo myocardium perfusion scintigraphy, from January 2003 through February 2004. Risk factors considered were: arterial blood hypertension, diabetes mellitus, dyslipidemia, obesity, previous coronary artery disease, tobacco smoking and family history of coronary diseases. All individuals were given detailed information about the study and were asked to sign the informed consent form. Individuals considered as pertaining to the coronary event group were those who, over a 12-month period, were admitted to hospital due to angina pectoris, acute myocardial infarction (AMI), coronary angioplasty and myocardium revascularization, in addition to death due to AMI. The remaining subjects were considered as coronary event-free patients.</p>
      <p>Of the 311 patients, 138 were referred for pharmacological exams due to: difficulty to ambulate, left bundle branch block, severe ventricular tachyarrhythmias, atrial fibrillation or pacemaker users, and were excluded from the study. The remaining 173 patients who underwent the exercise stress test (Bruce protocol) and myocardium perfusion scintigraphy with technetium-99m tetrofosmin (Tc <sup>99m</sup>), both on the same day, were included in the study. Of these, follow up could not be performed on eleven patients who ended up excluded from the study. </p>
      <p>Prospective follow up was performed on the 162 remaining patients for at least 12 months, for the purpose of assessing the presence of the following coronary events: angina pectoris, acute myocardial infarction, need to undergo percutaneous transluminal coronary angioplasty or myocardium revascularization and death. </p>
      <p>The Bruce treadmill protocol was applied to all individuals who underwent the exercise stress test. The Duke Treadmill Score index<sup>2</sup> of the exercise stress test was obtained using the following formula: Time (minutes) &#150; 5 X (ST-segment depression mm) &#150; 4 X (chest pain: 0 = no pain/ 1 = non-limiting pain/ 2 = limiting pain). Duke scores were set as: low risk &#150; index <underline>&gt;</underline> +5; intermediate risk between +4 to -10 and high risk <underline>&lt;</underline> -11. The two exercise stress testing experts who performed the exam assessed the ST-segment having no knowledge of the patient&#146;s clinical data, and they compared their results for the purpose of reducing subjective analysis errors. Time was obtained using a computerized system used to perform the exercise stress test (Ergo-S/Dixtal). Pain was assessed through a questionnaire completed by the patient during the exercise stress test, as described above.</p>
      <p>Myocardium perfusion scintigraphy with technetium-99m tetrofosmin (Tc <sup>99m</sup>) was performed with a one-day protocol. The resting image was the first one to be acquired and, six hours later, acquisition was repeated with patients exposed to physical stress on a treadmill. Tomography images (60 frames) were obtained on a continuous acquisition mode with patients at rest. Tomography images after physical stress were synchronized with the electrocardiogram to yield 8 frames per RR interval, totaling 480 frames per exam. SPECT results were considered as abnormal in view of any of the following: any transient perfusion defect at the LV wall (ischemia), any persistent perfusion defect at the LV wall in patients with no previous AMI or with hypokinesia associated, or otherwise, to an ejection fraction &lt; 50%, without any previous AMI. </p>
      <p>Standard deviation and standard error of the means were calculated between the groups with and without coronary events for both methods (DTS and SPECT) using the t-Student test for two independent variables. The Fisher Exact test was used for the analysis of variables of coronary risk. The prognostic sensitivity and specificity for both DTS and SPECT were determined and compared against each other using the "test of two independent proportions". Finally, the Kaplan-Meier method was used to obtain the event-free survival curves. The p&lt;0.05 value was considered as statistically significant. </p>
      <p>
        <bold>RESULTS</bold>
      </p>
      <p>Eighteen patients suffered coronary events within 12 months, whereas 144 did not.</p>
      <p><xref ref-type="table" rid="tab01-body2">Table 1</xref> shows that male gender, arterial hypertension, diabetes mellitus and greater mean age were statistically more common in the coronary event group. <xref ref-type="table" rid="tab02-body2">Table 2</xref> shows that there was no statistically significant difference between the proportions of risk factors studied among the populations with low-risk DTS score and those of intermediate/high-risk. As to scintigraphy, <xref ref-type="table" rid="tab03-body2">Table 3</xref> shows that there was a greater percentage of male, hypertensive, diabetic and previous coronariopathy patients in the group with altered scintigraphy. </p>
      <table-wrap id="tab01-body2">
        <graphic xlink:href="1678-4170-abc-87-02-0146-00012-gt01-en.jpg"/></table-wrap>
      <table-wrap id="tab02-body2">
        <graphic xlink:href="1678-4170-abc-87-02-0146-00012-gt02-en.jpg"/></table-wrap>
      <table-wrap id="tab03-body2">
        <graphic xlink:href="1678-4170-abc-87-02-0146-00012-gt03-en.jpg"/></table-wrap>
      <p>The number of patients with low, intermediate and high DTS, as well as the number of patients with normal and altered SPECT are shown in <xref ref-type="fig" rid="fig01-body2">figures 1</xref> and <xref ref-type="fig" rid="fig02-body2">2</xref>, respectively.</p>
      <fig id="fig01-body2">
        <graphic xlink:href="1678-4170-abc-87-02-0146-00012-gf01-en.jpg"/></fig>
      <fig id="fig02-body2">
        <graphic xlink:href="1678-4170-abc-87-02-0146-00012-gf02-en.jpg"/></fig>
      <p>The mean DTS obtained for the coronary event-free patients was +4.92 (CI 95%: +4.03 to +5.81). The mean DTS obtained for the group of patients who suffered coronary events was -0.27 (CI 95%: -3.97 to +3.91). As shown in <xref ref-type="fig" rid="fig03-body2">Figure 3</xref>, there was a statistically significant difference between the DTS mean in the two groups, with p&lt; 0.00069. The figure displays also the standard error and standard deviation. </p>
      <fig id="fig03-body2">
        <graphic xlink:href="1678-4170-abc-87-02-0146-00012-gf03-en.jpg"/></fig>
      <p>DTS sensitivity was 72.22% and that of SPECT was 77.78%; however, despite the greater sensitivity of the SPECT method, there was no statistical significance in relation to the DTS, with p=0.21. </p>
      <p>DTS specificity was 54.17% and that of CPM, 88.19%. The high specificity of SPECT compared to DTS was statistically relevant, with p&lt;0.0001.</p>
      <p>The mean ejection fraction obtained by SPECT functional analysis was 60.65% for event-free patients over 12 months, and 55.58% for those patients who suffered an event over the same period. There was no statistically relevance between the two groups, with p=0.08.</p>
      <p>Cumulative proportional event-free analysis over 12 months (Kaplan-Meier curves) revealed a clear difference between patients with normal SPECT and those with altered SPECT (p&lt;0.0001), as shown in <xref ref-type="fig" rid="fig04-body2">Figure 4</xref>. More than 95% of patients with normal SPECT did not experience any event over this period, whereas only 55% of patients with altered SPECT were event-free. The same analysis for DTS showed that, over 12 months, approximately 94% of the patients considered as pertaining to the low-risk group were event-free, whereas all those considered as high-risk patients suffered coronary events (p&lt;0.0001). Approximately 15% of the intermediate-risk patients suffered events during the 12-month period.</p>
      <fig id="fig04-body2">
        <graphic xlink:href="1678-4170-abc-87-02-0146-00012-gf04-en.jpg"/></fig>
      <p>
        <bold>DISCUSSION</bold>
      </p>
      <p>Balady et al<sup>4</sup>, reported that, in more than 3,000 asymptomatic patients at risk of coronary artery disease who were followed over a period longer than 18 years, the exercise stress test was able to help detecting those at higher risk, both for patients with high-risk Framingham score, as well as the low-risk scorers. Three variables obtained during the exercise stress testing were relevant: ST-segment depression &gt;1mm, exercise capacity in METs and lack of capacity to reach foreseen submaximal heart rate. For each MET added to performance under stress, there was a 13% reduction in the risk of events. It is worth mentioning that ST-segment depression and number of METs reached under stress, two of the most significant pieces of data which, separately, provided enhanced information on risk to the Framingham score, are also used to obtain the DTS score. The study above, indirectly and in a large population, demonstrated what DTS combined with exercise stress testing seeks to assess in a simple manner and to express numerically: the patient&#146;s risk of a coronary event. </p>
      <p>To date, no other study has compared DTS prognosis and that of SPECT among Brazilian patients, and this was what inspired us to conduct our study. </p>
      <p>The most important data in our study was that DTS sensitivity, although lower than that of SPECT, did not show any statistically significant difference. A meta-analysis described by Frohelicher et al<sup>1</sup> had already shown that DTS enhanced the accuracy of exercise stress testing to a level similar to that of thallium SPECT, though not greater than that of technetium SPECT. Another factor that could explain the statistical similarity between these methods is the fact that the analysis in this study was limited to 12 months, whereas most DTS and SPECT studies lasted more than 3 years. An atherosclerotic plaque, even a vulnerable one, does not always lead to a clinical event within a 12-month period, and it may become unstable even later on, depending on the control of risk factors. Stress testing methods, however, could detect early changes, for instance, perfusion deficit could be detected by SPECT. Patients with two or more risk factors for coronary artery disease were purposely chosen for this study, since this population is more susceptible to events and probably has a greater number of coronaries involved. It is known that exercise stress testing has greater sensitivity in multiartery disease patients, what may have increased DTS sensitivity. The same is true, however, for SPECT and with any other stress testing method<sup>5</sup>. Finally, a lower SPECT sensitivity may have been caused by the fact that patients able to ambulate and complete the exercise stress test have a better prognostic than patients who undergo pharmacological tests. In a group of infarction patients treated with thrombolytic agents, the GISSI-2 study showed that those who were not able to ambulate on a treadmill had a worse prognosis than those who completed at least the second stage of the Bruce protocol<sup>6</sup>. SPECT sensitivity, therefore, was not analyzed as a whole, but only in those patients who were able to exercise on a treadmill, i.e., those with better prognosis.</p>
      <p>On the other hand, DTS specificity was much lower in comparison to SPECT specificity, and this was statistically significant. This fact is hard to explain, since in a meta-analysis, Gianrossi et al<sup>7</sup> showed that exercise stress testing&#146;s specificity is greater than its sensitivity. An interesting bit of data from our study was that a significant portion of the event-free patients had intermediate-risk DTS due to ST-segment depression. A study conducted by Bugiardini et al<sup>8</sup> reported that 42 women who were followed up for 10 years, all of them with abnormal exercise stress tests associated to perfusion defects on SPECT, but with normal catheterization, had a high risk of developing coronary artery disease (injury seen on a new catheterization), acute myocardial infarction and death. Therefore, it was shown that abnormalities on exercise stress testing could be detected years before the atherosclerotic coronary lesion. Despite the fact that this study involved a small number of cases, it shed light on understanding the reasons why the exercise stress testing yields so many "false-positive" results. Alterations in the ST-segment in these cases were probably indications that these patients have important endothelial dysfunction and greater risks of future events. </p>
      <p>Only 3 patients had high-risk DTS (all of them developed events within one year). For this reason, they were evaluated together with the intermediate-risk group. Currently, some studies are underway to evaluate if the borderline DTS value among the group of intermediate-high risk patients is not underestimated. In other words, in order for the patient to reach a high-risk value (under "-11"), he/she should have very severe abnormalities on the ST-segment and, typically, experience angina during the exercise stress test. In the future, these studies will indicate the exact value to be considered as high-risk DTS. Perhaps a considerably greater cut-off value (closer to zero) may already indicate risk. Our study, for instance, showed, as seen in <xref ref-type="fig" rid="fig03-body2">Figure 3</xref>, that higher-risk patients who experienced an event within the 12-month period were those who had DTS below zero (&lt;00), with high statistical significance. Another important point corroborating this fact is that our study showed a relatively large number of events in patients with intermediate-risk DTS.</p>
      <p>The Kaplan-Meier curve (<xref ref-type="fig" rid="fig05-body2">Figure 5</xref>) clearly shows the difference between the DTS risk scores relative to the event-free period, mainly between high-risk to low-risk DTS, corroborating the reliability of this method to predict risk of future events. Despite this reliability, the DTS method has certain limitations. In patients with ST-segment depression detected as early as in the pre-test tracing, over 75 years of age, and in diabetic patients, DTS showed to have less diagnostic sensitivity. In these cases, association with other stress methods may benefit the patient. </p>
      <fig id="fig05-body2">
        <graphic xlink:href="1678-4170-abc-87-02-0146-00012-gf05-en.jpg"/></fig>
      <p><xref ref-type="fig" rid="fig04-body2">Figure 4</xref> shows that the individuals with normal SPECT had less than 5% of events in the period of this study, and many of them had intermediate-risk DTS. Indeed, SPECT is capable of determining which intermediate-risk patients have greater chances to experience coronary events. As mentioned by Beller et al <sup>10</sup>, intermediate-DTS patients who presented a normal SPECT had a mortality rate under 0.4% per year, whereas those with abnormal SPECT had a mortality rate of 8.9% per year. SPECT had a significant role in detecting those individuals with greater risk, which was consistent with several studies conducted in the past<sup>11-13</sup>.</p>
      <p>The main limitation in our study was the relatively small number of cases. A study with a larger number of cases could not only corroborate our findings more efficiently, but also determine data obtained for several subgroups of patients. For instance, we could have separated them according to their risk factors and determine the greater-risk DTS for each one. Another constraint, already mentioned, was the evaluation of the group of patients referred for SPECT and who were able to exercise on a treadmill, i.e., those with better prognosis. This may have affected the comparative evaluation of these two exercise stress methods. Finally, another limitation worth mentioning in this study is the subjective analysis of the examiner to determine ST-segment during the exercise stress testing, as well as SPECT imaging. In order to minimize errors, more than one examiner performed data acquisition, and, more importantly, neither knew the other&#146;s results (exercise stress testing and SPECT).</p>
      <p>In conclusion, our study showed DTS to be as sensitive as SPECT in detecting patients with greater risk of coronary events within 12 months, mainly individuals who had DTS under zero, even if asymptomatic. Many of these individuals, classified as intermediate-risk patients, warrant special attention from their clinical physicians. It is suggested that they be referred to undergo other stress methods, such as SPECT for diagnosis confirmation. Those presenting high-risk DTS should immediately be evaluated and possibly referred for coronary angiography.</p>
      <p>
        <bold>Acknowledgements </bold>
      </p>
      <p>To Avanildo Rubert, Patr&#237;cia Marina Piffar, Adair Obreg&#227;o de Lima, Jo&#227;o Maria da Silva, Roberto Ferreira da Silva, Leoni Matzenbacher, Sandro Afonso, radiology technicians, and to S&#237;lvia Paula Cola&#231;o and Jocilene Raspzak Gorri, secretaries, for their dedication and respect shown towards the patients in this study. </p>
      <p>
        <bold>Potencial Conflict of Interest</bold>
      </p>
      <p>No potential conflict of interest relevant to this article was reported.</p>
      <p>
        <bold>REFERENCES</bold>
      </p>
      <p>
        <fn id="end-body2" fn-type="corresp">
          <label>
            <bold>Mailing Address:</bold>
          </label>
          <p> Carlos Alberto Gasperin </p>
          <p> Rua Gon&#231;alves Dias, 655</p>
          <p> 80240-340 &#150; Curitiba, PR - Brazil</p>
          <p> E-mail: </p>
          <p>
            <email xlink:href="acgasperin@cendicor.com.br">acgasperin@cendicor.com.br</email>
          </p>
        </fn>
      </p>
      <p> Received on 10/11/05</p>
      <p> Accepted on 03/24/06</p>
    </body>
  </sub-article>
</article>
