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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">cbByxwNCtnD4WxPYkwR8jMB</article-id>
      <article-id pub-id-type="other">00007</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2008001600007</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(08)09100407</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2008001600007</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Avalia&#231;&#227;o da prescri&#231;&#227;o de exerc&#237;cios pela cintilografia mioc&#225;rdica na reabilita&#231;&#227;o de coronariopatas</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Meneghelo</surname>
            <given-names>Romeu S.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Magalh&#227;es</surname>
            <given-names>H&#233;lio M.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Smanio</surname>
            <given-names>Paola E. P.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Fuchs</surname>
            <given-names>Angela R. C. N.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ferraz</surname>
            <given-names>Almir S.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Buchler</surname>
            <given-names>Rica D. D.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Buglia</surname>
            <given-names>Susimeire</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mastrocolla</surname>
            <given-names>Luiz E.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Thom</surname>
            <given-names>Anneliese F.</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>10</month>
        <year>2008</year>
      </pub-date>
      <volume>91</volume>
      <issue>4</issue>
      <fpage>245</fpage>
      <lpage>251</lpage>
      <history>
        <date date-type="accepted">
          <day>01</day>
          <month>02</month>
          <year>2008</year>
        </date>
        <date date-type="rev-recd">
          <day>29</day>
          <month>01</month>
          <year>2008</year>
        </date>
        <date date-type="received">
          <day>23</day>
          <month>10</month>
          <year>2007</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: Recomenda-se que a intensidade dos exerc&#237;cios na reabilita&#231;&#227;o de coronariopatas n&#227;o deva produzir isquemia mioc&#225;rdica. OBJETIVO: Comparar a capacidade da cintilografia tomogr&#225;fica do mioc&#225;rdio com a do eletrocardiograma na detec&#231;&#227;o de isquemia durante sess&#227;o de reabilita&#231;&#227;o. M&#201;TODOS: Vinte e seis pacientes coronariopatas, em programa de reabilita&#231;&#227;o e com cintilografia pr&#233;via com hipocapta&#231;&#227;o transit&#243;ria, receberam nova inje&#231;&#227;o de MIBI-Tc-99m durante uma sess&#227;o de treinamento, quando tamb&#233;m foram monitorizados pela eletrocardiografia din&#226;mica. As cintilografias de repouso, ap&#243;s teste ergom&#233;trico em esteira e ap&#243;s sess&#227;o de reabilita&#231;&#227;o, foram analisadas de forma semiquantitativa utilizando-se um escore, de 0 a 4, classificando cada um dos segmentos escolhidos (0 = normal; 1 = hipocapta&#231;&#227;o discreta; 2 = moderada; 3 = intensa; 4 = aus&#234;ncia da capta&#231;&#227;o). RESULTADOS: As m&#233;dias dos somat&#243;rios dos escores encontrados foram: repouso = 12,9; ap&#243;s teste em esteira = 19,3; ap&#243;s sess&#227;o de reabilita&#231;&#227;o = 15,1. Houve diferen&#231;as estatisticamente significativas entre elas. Uma an&#225;lise individual mostrou que em 14 casos (53,8 %) foi identificado algum grau de hipocapta&#231;&#227;o durante a reabilita&#231;&#227;o, e em 12 (46,6%), n&#227;o. Monitoriza&#231;&#227;o com sistema Holter n&#227;o revelou, em nenhum caso, depress&#227;o do segmento ST, igual ou maior do que 1 mm. CONCLUS&#195;O: Exerc&#237;cios prescritos em doentes coronariopatas, conforme recomenda&#231;&#245;es da literatura, podem desencadear isquemia mioc&#225;rdica, avaliada pela cintilografia, durante sess&#227;o de reabilita&#231;&#227;o.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Coronariopatia</kwd>
        <kwd>terapia por exerc&#237;cio</kwd>
        <kwd>cintilografia</kwd>
        <kwd>Tecn&#233;cio</kwd>
        <kwd>isquemia mioc&#225;rdica</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>11</day>
        <month>11</month>
        <year>2008</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>ARTIGO ORIGINAL </p>
    <p> CORONARIOPATIA AGUDA</p>
    <p>
      <bold>Avalia&#231;&#227;o da prescri&#231;&#227;o de exerc&#237;cios pela cintilografia mioc&#225;rdica na reabilita&#231;&#227;o de coronariopatas</bold>
    </p>
    <p>
      <bold>Romeu S. Meneghelo; H&#233;lio M. Magalh&#227;es; Paola E. P. Smanio; Angela R. C. N. Fuchs; Almir S. Ferraz; Rica D. D. Buchler; Susimeire Buglia; Luiz E. Mastrocolla; Anneliese F. Thom</bold>
    </p>
    <p> Instituto Dante Pazzanese de Cardiologia, S&#227;o Paulo, SP - Brasil</p>
    <p>
      <xref ref-type="corresp" rid="back">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>FUNDAMENTO:</bold> Recomenda-se que a intensidade dos exerc&#237;cios na reabilita&#231;&#227;o de coronariopatas n&#227;o deva produzir isquemia mioc&#225;rdica. </p>
    <p><bold>OBJETIVO: </bold> Comparar a capacidade da cintilografia tomogr&#225;fica do mioc&#225;rdio com a do eletrocardiograma na detec&#231;&#227;o de isquemia durante sess&#227;o de reabilita&#231;&#227;o. </p>
    <p><bold>M&#201;TODOS: </bold> Vinte e seis pacientes coronariopatas, em programa de reabilita&#231;&#227;o e com cintilografia pr&#233;via com hipocapta&#231;&#227;o transit&#243;ria, receberam nova inje&#231;&#227;o de MIBI-Tc-99m durante uma sess&#227;o de treinamento, quando tamb&#233;m foram monitorizados pela eletrocardiografia din&#226;mica. As cintilografias de repouso, ap&#243;s teste ergom&#233;trico em esteira e ap&#243;s sess&#227;o de reabilita&#231;&#227;o, foram analisadas de forma semiquantitativa utilizando-se um escore, de 0 a 4, classificando cada um dos segmentos escolhidos (0 = normal; 1 = hipocapta&#231;&#227;o discreta; 2 = moderada; 3 = intensa; 4 = aus&#234;ncia da capta&#231;&#227;o). </p>
    <p><bold>RESULTADOS:</bold> As m&#233;dias dos somat&#243;rios dos escores encontrados foram: repouso = 12,9; ap&#243;s teste em esteira = 19,3; ap&#243;s sess&#227;o de reabilita&#231;&#227;o = 15,1. Houve diferen&#231;as estatisticamente significativas entre elas. Uma an&#225;lise individual mostrou que em 14 casos (53,8 %) foi identificado algum grau de hipocapta&#231;&#227;o durante a reabilita&#231;&#227;o, e em 12 (46,6%), n&#227;o. Monitoriza&#231;&#227;o com sistema Holter n&#227;o revelou, em nenhum caso, depress&#227;o do segmento ST, igual ou maior do que 1 mm. </p>
    <p><bold>CONCLUS&#195;O:</bold> Exerc&#237;cios prescritos em doentes coronariopatas, conforme recomenda&#231;&#245;es da literatura, podem desencadear isquemia mioc&#225;rdica, avaliada pela cintilografia, durante sess&#227;o de reabilita&#231;&#227;o.</p>
    <p><bold>Palavras-chave: </bold> Coronariopatia/reabilita&#231;&#227;o, terapia por exerc&#237;cio/m&#233;todos, cintilografia, Tecn&#233;cio, isquemia mioc&#225;rdica.</p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p>O conceito de reabilita&#231;&#227;o cardiovascular confunde-se hoje com o de preven&#231;&#227;o secund&#225;ria, especialmente na doen&#231;a arterial coron&#225;ria<sup>1</sup>. Entretanto, o exerc&#237;cio f&#237;sico &#233; fundamento b&#225;sico dos programas e, isoladamente, &#233; capaz de propiciar benef&#237;cios como o desaparecimento ou minimiza&#231;&#227;o dos sintomas<sup>2,3</sup> e as adapta&#231;&#245;es perif&#233;ricas<sup>4-6</sup> que determinam aumento da capacidade f&#237;sica<sup>7-10</sup> capazes de reduzir as manifesta&#231;&#245;es isqu&#234;micas para cargas subm&#225;ximas. Ele tem ainda papel destacado no aux&#237;lio ao combate dos fatores de risco: diabete, sedentarismo, hipertens&#227;o, dislipidemias e obesidade. A despeito dos benef&#237;cios incontestes, exercitar pacientes coronariopatas pode ser potencialmente mal&#233;fico. Eventos coron&#225;rios agudos podem levar a morte s&#250;bita, embora de pequena incid&#234;ncia<sup>11</sup>. A prescri&#231;&#227;o de exerc&#237;cios que propiciam longos per&#237;odos de isquemia mioc&#225;rdica pode ser o substrato para o desencadeamento de fibrila&#231;&#227;o ventricular e poderia, a longo prazo, propiciar necrose mioc&#225;rdica<sup>12</sup>, considerando-se trabalhos realizados em animais<sup>13,14</sup>. Portanto, a intensidade dos exerc&#237;cios prescritos deve ficar abaixo daquela capaz de produzir isquemia mioc&#225;rdica, geralmente avaliada por sintomas ou depress&#245;es do segmento ST. Essa premissa &#233; recomendada por diretrizes vigentes<sup>15</sup>. A nossa prefer&#234;ncia, entre as diversas formas de se prescrever esses exerc&#237;cios, &#233; limit&#225;-los &#224; capacidade funcional &#250;til<sup>16</sup>, que &#233; o maior n&#237;vel de esfor&#231;o que n&#227;o causa sintomas, altera&#231;&#245;es cl&#237;nicas, eletrocardiogr&#225;ficas e hemodin&#226;micas. Nos pacientes sem essas altera&#231;&#245;es, a escala de Borg<sup>17</sup> entre 13 a 15 &#233; utilizada, o que corresponde &#224; sensa&#231;&#227;o subjetiva de ligeiramente cansativo a cansativo. A maior sensibilidade da cintilografia de perfus&#227;o mioc&#225;rdica para diagnosticar isquemia mioc&#225;rdica, em rela&#231;&#227;o &#224; ocorr&#234;ncia de angina e &#224;s depress&#245;es do segmento ST, propiciou o interesse em se estudar o n&#237;vel de seguran&#231;a dessa prescri&#231;&#227;o. O objetivo do presente trabalho foi comparar a capacidade da cintilografia tomogr&#225;fica do mioc&#225;rdio com a do eletrocardiograma, na detec&#231;&#227;o de isquemia durante sess&#227;o de reabilita&#231;&#227;o. O estudo foi aprovado pelo comit&#234; de &#233;tica da institui&#231;&#227;o.</p>
    <p>
      <bold>Relato do Caso</bold>
    </p>
    <p>Foram selecionados, entre 143 pacientes que participavam do programa de reabilita&#231;&#227;o supervisionada em nossa institui&#231;&#227;o, 39 que apresentavam: tempo de perman&#234;ncia no programa superior a seis meses; diagn&#243;stico de doen&#231;a arterial coron&#225;ria feito por cinecoronariografia pr&#233;via com pelo menos uma les&#227;o obstrutiva, igual ou maior do que 70%, numa das tr&#234;s principais art&#233;rias coron&#225;rias; depress&#227;o do segmento ST, desencadeado pelo esfor&#231;o, de pelo menos um mil&#237;metro em teste ergom&#233;trico realizado no intervalo de um ano antes; aus&#234;ncia de bloqueio de ramo esquerdo e de pr&#233;-excita&#231;&#227;o ao eletrocardiograma de 12 deriva&#231;&#245;es. Ap&#243;s os respectivos consentimentos informados terem sido assinados, foi realizada uma cintilografia mioc&#225;rdica com MIBI-Tc-99m, associada ao teste ergom&#233;trico em esteira no protocolo de Bruce. No prazo n&#227;o superior a uma semana, foi realizada cintilografia de repouso. Por an&#225;lise visual, foram selecionados os casos que apresentavam estudo cintilogr&#225;fico compat&#237;vel com isquemia mioc&#225;rdica transit&#243;ria, em pelo menos um segmento do ventr&#237;culo esquerdo. Nessa an&#225;lise inicial da cintilografia, foram exclu&#237;dos 13 casos, nos quais n&#227;o se conseguiu diagnosticar evidente isquemia transit&#243;ria induzida pelo exerc&#237;cio. Assim, os outros 26 pacientes prosseguiram no estudo e tinham idades entre 49 e 81 anos (m&#233;dia = 63,2 anos). Um total de 13 pacientes (50%) havia sido submetido &#224; cirurgia de revasculariza&#231;&#227;o. Infarto do mioc&#225;rdio havia ocorrido em 10 pacientes (38,5%), n&#227;o submetidos a cirurgia ou angioplastia posteriormente. Angioplastia na fase aguda de infarto do mioc&#225;rdio havia sido feita em dois pacientes (7,7%) e angioplastia eletiva, em um paciente (3,8%). Entre os 10 pacientes n&#227;o submetidos a revasculariza&#231;&#227;o, cinco (50%) tinham les&#245;es uniarteriais; um (10%) em duas art&#233;rias; e quatro (40%) em tr&#234;s vasos. As cinecoronariografias, pr&#233;vias aos procedimentos de revasculariza&#231;&#227;o, nos demais 16 pacientes, mostraram que dois (12,5 %) tinham les&#245;es uniarteriais; oito (50 %) biarterias; e seis (37,5 %) triarteriais.</p>
    <p>
      <bold>M&#233;todos</bold>
    </p>
    <p>Todos os pacientes, depois das cintilografias iniciais, foram conectados a um gravador de eletrocardiografia din&#226;mica, antes do in&#237;cio da sess&#227;o de reabilita&#231;&#227;o destinada &#224; obten&#231;&#227;o de nova cintilografia associada ao exerc&#237;cio prescrito. A grava&#231;&#227;o, em gravador de fita cassete da Cardios<sup>&#174;</sup>, nas deriva&#231;&#245;es MC2 e MC5, cobriu toda a sess&#227;o. Antes da fase denominada de aer&#243;bica cont&#237;nua, realizada por 20 minutos em bicicleta ergom&#233;trica com a carga prescrita, foi cateterizada uma veia perif&#233;rica, de um dos membros superiores. No pen&#250;ltimo minuto do exerc&#237;cio foi administrada a dose de MIBI-Tc-99m e se acionou o bot&#227;o de eventos para que se pudesse avaliar com precis&#227;o o tra&#231;ado eletrocardiogr&#225;fico da ocasi&#227;o. Cerca de uma hora ap&#243;s, foi obtida nova cintilografia de esfor&#231;o. Tra&#231;ados eletrocardiogr&#225;ficos de cinco a 10 segundos, no in&#237;cio da grava&#231;&#227;o e no momento em que foi injetado o MIBI-Tc-99m foram identificados e impressos em papel para que o segmento ST fosse analisado, visualmente, em complexos sucessivos, com linha de base est&#225;vel.</p>
    <p>
      <bold>Teste ergom&#233;trico em bicicleta para prescri&#231;&#227;o do exerc&#237;cio</bold>
    </p>
    <p>O teste pr&#233;vio para a prescri&#231;&#227;o do exerc&#237;cio, sinal e/ou sintoma limitado e na vig&#234;ncia da medica&#231;&#227;o em uso foi realizado previamente em bicicleta ergom&#233;trica mec&#226;nica, com carga inicial de 25 watts e incrementos a cada cinco minutos de 25 watts. A prescri&#231;&#227;o do exerc&#237;cio de reabilita&#231;&#227;o teve como base a carga e a freq&#252;&#234;ncia card&#237;acas do final da etapa do teste imediatamente anterior &#224;quela que produziu sintomas, altera&#231;&#245;es hemodin&#226;micas ou eletrocardiogr&#225;ficas. Nos indiv&#237;duos que n&#227;o apresentaram sintomas e nenhuma altera&#231;&#227;o cl&#237;nica e eletrocardiogr&#225;fica, a carga e a freq&#252;&#234;ncia card&#237;acas foram aquelas em que o paciente apresentou n&#237;vel de percep&#231;&#227;o do esfor&#231;o entre 13 a 15 da escala de Borg, ou seja, entre ligeiramente cansativo e cansativo.</p>
    <p>
      <bold>Cintilografias mioc&#225;rdicas</bold>
    </p>
    <p>As cintilografias de perfus&#227;o do mioc&#225;rdio foram realizadas pela t&#233;cnica de tomografia por emiss&#227;o de f&#243;ton &#250;nico (SPECT), usando-se como indicador de perfus&#227;o a 2-metoxi--isobutil-isonitrila marcada com tecn&#233;cio-99m (MIBI-Tc-99m).</p>
    <p>As interpreta&#231;&#245;es das cintilografias foram feitas por consenso de dois observadores, utilizando-se um sistema de pontua&#231;&#227;o para cada um dos 20 segmentos de quatro cortes tomogr&#225;ficos assim escolhidos: corte do eixo menor apical, corte do eixo menor medial, corte do eixo menor basal, corte medial do eixo maior vertical. O segmento de maior intensidade de capta&#231;&#227;o de radioatividade, para cada corte, de cada uma das cintilografias, foi escolhido como refer&#234;ncia. A esse segmento foi dado o valor 0 (zero). Os segmentos adjacentes do mesmo corte receberam pontua&#231;&#227;o segundo o seguinte crit&#233;rio:</p>
    <p> &#149; 0 = se estavam com a mesma intensidade de capta&#231;&#227;o da radioatividade;</p>
    <p>&#149; 1 = se havia uma hipocapta&#231;&#227;o discreta;</p>
    <p>&#149; 2 = se havia uma hipocapta&#231;&#227;o moderada;</p>
    <p>&#149; 3 = se havia uma hipocapta&#231;&#227;o intensa; e</p>
    <p>&#149; 4 = se havia aus&#234;ncia de capta&#231;&#227;o.</p>
    <p>O somat&#243;rio da pontua&#231;&#227;o dada a cada um dos segmentos dos quatro cortes escolhidos foi definida como o escore de cada cintilografia, duas de esfor&#231;o e uma de repouso. Com esse m&#233;todo, a igualdade entre os escores de esfor&#231;o e de repouso indica a aus&#234;ncia de hipocapta&#231;&#227;o induzida pelo esfor&#231;o e, conseq&#252;entemente, aus&#234;ncia de isquemia induzida pelo esfor&#231;o. Maior escore no esfor&#231;o do que no repouso indica a presen&#231;a de hipocapta&#231;&#227;o induzida pelo esfor&#231;o e, conseq&#252;entemente, isquemia induzida pelo esfor&#231;o.</p>
    <p>
      <bold>Sess&#227;o de reabilita&#231;&#227;o supervisionada</bold>
    </p>
    <p>A sess&#227;o de reabilita&#231;&#227;o na qual foi administrada a dose de MIBI-Tc-99m para a obten&#231;&#227;o da segunda cintilografia de esfor&#231;o foi semelhante a todas as sess&#245;es que os pacientes cumpriam, e foi assim constitu&#237;da:</p>
    <p>a) Aquecimento: caminhada, a passo normal, durante cinco minutos;</p>
    <p>b) Fase aer&#243;bia com pausa ativa: caminhadas de dois a tr&#234;s minutos, intercaladas com pequenas corridas de um a dois minutos, durante 15 minutos;</p>
    <p>c) Fase aer&#243;bica cont&#237;nua: exerc&#237;cio em bicicleta ergom&#233;trica mec&#226;nica com carga aplicada conforme a prescri&#231;&#227;o baseada na capacidade funcional &#250;til, com dura&#231;&#227;o de 20 minutos;</p>
    <p>d) Exerc&#237;cios localizados de resist&#234;ncia e alongamento durante 20 minutos.</p>
    <p>
      <bold>An&#225;lise estat&#237;stica</bold>
    </p>
    <p>As vari&#225;veis referentes aos testes ergom&#233;tricos em esteira e em bicicleta, a carga prescrita e a freq&#252;&#234;ncia card&#237;aca correspondente, a freq&#252;&#234;ncia card&#237;aca no in&#237;cio da monitoriza&#231;&#227;o pelo sistema Holter e a freq&#252;&#234;ncia card&#237;aca no momento da inje&#231;&#227;o foram resumidas sob a forma de m&#233;dias e desvios-padr&#227;o. A compara&#231;&#227;o entre a freq&#252;&#234;ncia card&#237;aca prescrita e a freq&#252;&#234;ncia card&#237;aca observada quando da inje&#231;&#227;o do MIBI-Tc-99m foi feita pelo teste <italic>t</italic> de Student pareado. Os escores obtidos nas cintilografias de repouso, ap&#243;s teste ergom&#233;trico em esteira e durante a sess&#227;o de reabilita&#231;&#227;o, foram apresentados sob a forma de m&#233;dias e intervalos de confian&#231;a de 95% (IC95%). As compara&#231;&#245;es entre os escores nas tr&#234;s situa&#231;&#245;es foram feitas pela t&#233;cnica de An&#225;lise de Vari&#226;ncia (ANOVA) com medidas repetidas. Para localizar as diferen&#231;as, foi utilizado o m&#233;todo de compara&#231;&#245;es m&#250;ltiplas de Bonferroni.</p>
    <p>
      <bold>Resultados</bold>
    </p>
    <p>
      <bold>Teste ergom&#233;trico em esteira para obten&#231;&#227;o da cintilografia mioc&#225;rdica</bold>
    </p>
    <p>O tempo m&#233;dio de exerc&#237;cio no protocolo de Bruce foi de 7,4 minutos (DP=2,1). A m&#233;dia da freq&#252;&#234;ncia card&#237;aca variou de 73,6 bpm em repouso a 137,1 bpm (DP=18,5) no pico do esfor&#231;o. A m&#233;dia da press&#227;o arterial em repouso foi de 141,3 (DP=21,3) / 83,4 (DP=8,9) mmHg, atingindo 197,3 (DP=32)/82,6 (DP=7,2) mmHg no pico do exerc&#237;cio (<xref ref-type="table" rid="t1">tab. 1</xref>). Todos os pacientes apresentaram depress&#227;o do segmento ST desencadeado pelo esfor&#231;o, mas em sete (27 %) a depress&#227;o ficou entre 0,5 e 1 mm. Em 19 casos (73%) a depress&#227;o foi igual ou maior do que 1 mm. O valor m&#233;dio da depress&#227;o foi de 1,31 mm (DP = 0,74). Angina do peito foi o motivo da interrup&#231;&#227;o do exerc&#237;cio em quatro pacientes (15,3%) e exaust&#227;o nos outros 22 (84,7%).</p>
    <p content-type="asset">
      <table-wrap id="t1">
        <graphic xlink:href="1678-4170-abc-91-04-0245-00007-gt01.jpg"/></table-wrap>
    </p>
    <p>
      <bold>Teste ergom&#233;trico em bicicleta para prescri&#231;&#227;o do exerc&#237;cio</bold>
    </p>
    <p>A carga m&#233;dia m&#225;xima atingida foi de 76 watts (DP = 14,9). A m&#233;dia da freq&#252;&#234;ncia card&#237;aca variou de 71,3 bpm (DP = 12,8) em repouso a 111,7 bpm (DP = 22,9), no pico do esfor&#231;o. Os valores m&#233;dios da press&#227;o arterial variaram de 129,8 (DP=17,5)/75,5 (DP = 10,1) (mmHg) nos controles pr&#233;vios a 183,6 (DP = 22,5)/85,4 mmHg (DP = 15,4) no pico do exerc&#237;cio (<xref ref-type="table" rid="t1">tab. 1</xref>).</p>
    <p>
      <bold>ResultadosPrescri&#231;&#227;o baseada na capacidade funcional &#250;til</bold>
    </p>
    <p>A carga m&#233;dia prescrita foi de 49 watts (DP = 8,6). A freq&#252;&#234;ncia card&#237;aca m&#233;dia para o treinamento foi de 104,7 bpm (DP = 15,7) o que representou, tamb&#233;m em m&#233;dia, 66,7% (DP = 9,4) da freq&#252;&#234;ncia card&#237;aca m&#225;xima te&#243;rica para a idade (<xref ref-type="table" rid="t1">tab. 1</xref>).</p>
    <p>
      <bold>Monitoriza&#231;&#227;o eletrocardiogr&#225;fica din&#226;mica</bold>
    </p>
    <p>Depress&#227;o do segmento ST menor do que um mil&#237;metro ou depress&#227;o adicional tamb&#233;m menor do que 1 mm ocorreu em apenas tr&#234;s casos (11,5%) no momento da inje&#231;&#227;o do MIBI-Tc-99m durante a sess&#227;o de reabilita&#231;&#227;o. Em nenhum doente houve depress&#227;o igual ou maior do que um mil&#237;metro. A m&#233;dia da freq&#252;&#234;ncia card&#237;aca em repouso foi de 82,7 bpm (DP = 14,3) e no momento da inje&#231;&#227;o foi de 102,6 bpm (DP = 15,1). N&#227;o houve diferen&#231;a estatisticamente significativa entre essa freq&#252;&#234;ncia card&#237;aca observada no momento da inje&#231;&#227;o do MIBI-Tc-99m e da freq&#252;&#234;ncia card&#237;aca prescrita para este momento cuja m&#233;dia foi de 104,7 (DP = 15,6). (P = 0,45).</p>
    <p>
      <bold>Cintilografias mioc&#225;rdicas</bold>
    </p>
    <p>Na <xref ref-type="table" rid="tab2">tabela 2</xref> est&#227;o expressos os valores dos escores obtidos com a interpreta&#231;&#227;o das imagens cintilogr&#225;ficas de repouso, de esfor&#231;o em esteira e de exerc&#237;cio em bicicleta ergom&#233;trica, durante sess&#227;o de reabilita&#231;&#227;o. A m&#233;dia dos escores observados em repouso foi de 12,9 (DP = 9,1), durante o esfor&#231;o em esteira foi de 19,3 (DP = 10), e durante a reabilita&#231;&#227;o de 15,1 (DP = 10,2).</p>
    <table-wrap id="tab2">
      <graphic xlink:href="1678-4170-abc-91-04-0245-00007-gt02.jpg"/></table-wrap>
    <p>A diferen&#231;a m&#233;dia entre o escore de repouso e o escore da cintilografia associada ao teste em esteira foi de 6,3 IC (95%) [4,3; 8,3] (P&lt;0,0001). Entre o escore de repouso e o escore obtido com a cintilografia realizada quando da sess&#227;o de reabilita&#231;&#227;o foi de 2,2 IC (95%) [0,8; 3,6] (P&lt;0,001). A diferen&#231;a m&#233;dia entre o escore da cintilografia durante sess&#227;o de reabilita&#231;&#227;o e o escore da cintilografia associada ao teste em esteira foi de 4,1 IC (95%) [2,3; 5,8] (P&lt;0,001). Analisados individualmente, todos os casos apresentaram maior escore na cintilografia de esfor&#231;o em esteira do que no repouso, uma vez que essa condi&#231;&#227;o era determinante para que o caso fosse inclu&#237;do no estudo. Entretanto, durante a sess&#227;o de reabilita&#231;&#227;o 12 pacientes (46,2%) apresentaram o mesmo escore obtido no repouso. Em 11 (42,3%), o escore obtido no exerc&#237;cio em bicicleta foi maior do que o escore do repouso, mas menor do que o escore observado no teste em esteira. Um total de tr&#234;s pacientes (11,5%) tiveram o mesmo escore nos dois testes. Portanto, em 14 casos (53,8%), o escore observado na cintilografia durante sess&#227;o de reabilita&#231;&#227;o foi maior do que no repouso, indicando a presen&#231;a de hipocapta&#231;&#227;o transit&#243;ria durante a sess&#227;o de reabilita&#231;&#227;o. Sugestiva isquemia mioc&#225;rdica n&#227;o ocorreu em 12 casos (46,6%) que tiveram o mesmo escore na cintilografia mioc&#225;rdica durante a sess&#227;o de reabilita&#231;&#227;o e no repouso.</p>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>As regras atualmente vigentes determinam que a prescri&#231;&#227;o de exerc&#237;cio para pacientes com doen&#231;a coron&#225;ria deve ser feita em n&#237;veis que n&#227;o produzam isquemia mioc&#225;rdica caracterizada por angina do peito e ou depress&#227;o do segmento ST<sup>15</sup>. A vigil&#226;ncia dessa regra pode ser feita facilmente hoje pela monitoriza&#231;&#227;o cl&#237;nica e eletrocardiogr&#225;fica numa sess&#227;o de reabilita&#231;&#227;o. Entretanto, em algumas condi&#231;&#245;es como: ap&#243;s infarto agudo do mioc&#225;rdio, hipertrofias ventriculares, pr&#233;vias altera&#231;&#245;es do segmento ST e outras, a cintilografia de perfus&#227;o mioc&#225;rdica permite que se avalie com mais acur&#225;cia a presen&#231;a de eventual isquemia mioc&#225;rdica, no &#226;mbito da reabilita&#231;&#227;o cardiovascular. Nesse sentido, a presente investiga&#231;&#227;o &#233; in&#233;dita e amplia a eventual utiliza&#231;&#227;o da cardiologia nuclear.</p>
    <p>Os doentes selecionados para a investiga&#231;&#227;o n&#227;o constitu&#237;am um grupo homog&#234;neo quanto &#224;s condi&#231;&#245;es cl&#237;nicas no momento da inclus&#227;o, mas todos eram coronariopatas, identificados por pr&#233;via cinecoronariografia e, portanto, com justificativa para apresentarem cintilografia mioc&#225;rdica com hipocapta&#231;&#227;o induzida pelo esfor&#231;o. Um total de 10 pacientes (38,5%) n&#227;o tinha sido submetido a nenhum tipo de revasculariza&#231;&#227;o, e os demais 16 (61,5%) eram revascularizados por cirurgia e/ou angioplastia. Embora, pela hist&#243;ria cl&#237;nica, em 13 havia sido identificado claramente epis&#243;dio de infarto do mioc&#225;rdio, em 23 foi reconhecido escore maior do que zero na cintilografia de repouso, indicando que apenas tr&#234;s n&#227;o tinham infarto do mioc&#225;rdio pregresso. Essas caracter&#237;sticas conferem ao grupo similaridade com os grupos em reabilita&#231;&#227;o segundo as indica&#231;&#245;es atuais para a reabilita&#231;&#227;o supervisionada.</p>
    <p>Na escolha do protocolo utilizado, procurou-se modificar o m&#237;nimo poss&#237;vel a sess&#227;o de reabilita&#231;&#227;o, para que os resultados n&#227;o sofressem interfer&#234;ncia de procedimentos complexos que gerassem inseguran&#231;a e ansiedade nos pacientes. Diferentemente de uma sess&#227;o habitual, foi instalado um gravador de Holter e se fez uma cateteriza&#231;&#227;o de veia perif&#233;rica, apenas no in&#237;cio do exerc&#237;cio em bicicleta. Cuidou-se tamb&#233;m para que o ambiente da sess&#227;o n&#227;o apresentasse caracter&#237;sticas de um grande experimento. Contudo, n&#227;o se pode afastar a hip&#243;tese de que algum grau de ansiedade possa ter interferido nos resultados.</p>
    <p>As caracter&#237;sticas do teste em bicicleta para prescri&#231;&#227;o do exerc&#237;cio, utilizado na nossa institui&#231;&#227;o, empregado tamb&#233;m nessa investiga&#231;&#227;o, t&#234;m como escopo identificar valores de freq&#252;&#234;ncia card&#237;aca e altera&#231;&#245;es eletrocardiogr&#225;ficas, as mais pr&#243;ximas poss&#237;veis do estado est&#225;vel, numa determinada carga. Minimizam-se assim os erros cometidos quando a prescri&#231;&#227;o &#233; feita a partir de um teste com dura&#231;&#227;o mais curta do que cinco minutos em cada etapa, empregados na maioria dos protocolos convencionais. Os valores m&#233;dios da freq&#252;&#234;ncia card&#237;aca preconizada de 104,7 (DP 15,6) e os valores m&#233;dios observados no 19&#186; minuto do exerc&#237;cio em bicicleta na sess&#227;o de reabilita&#231;&#227;o de 102,6 (DP=15,1) n&#227;o foram diferentes do ponto de vista estat&#237;stico (p&lt;0,005). Esses dados mostram a boa precis&#227;o do teste de prescri&#231;&#227;o em prever os valores de freq&#252;&#234;ncia card&#237;aca depois de 20 minutos de esfor&#231;o, numa carga prescrita para o mesmo erg&#244;metro, em ambas as situa&#231;&#245;es.</p>
    <p>Os valores m&#233;dios da carga prescrita de 49 watts (DP = 8,6) e de freq&#252;&#234;ncia card&#237;aca de 104,7 (DP = 15,6), correspondendo a um percentual m&#233;dio da freq&#252;&#234;ncia card&#237;aca m&#225;xima de 66,7% (DP = 9,4), s&#227;o relativamente modestos para o treinamento de indiv&#237;duos normais, mas perfeitamente aceit&#225;veis para a reabilita&#231;&#227;o de coronariopatas, segundo os n&#237;veis de prescri&#231;&#245;es recomendados por diretrizes em vigor<sup>15</sup>.</p>
    <p>O emprego da monitoriza&#231;&#227;o eletrocardiogr&#225;fica, no presente estudo, possibilitou, de modo simples e mais acurado, a obten&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca e a avalia&#231;&#227;o do segmento ST quando da inje&#231;&#227;o do MIBI-Tc-99m. O sistema utilizado permitiu boa correla&#231;&#227;o dessas duas vari&#225;veis, uma vez que, no momento da inje&#231;&#227;o, foi acionado o bot&#227;o de eventos que grava um sinal eletr&#244;nico coincidente com o tra&#231;ado eletrocardiogr&#225;fico daquele instante.</p>
    <p>As m&#233;dias dos escores observados nas cintilografias de repouso, esteira e bicicleta durante sess&#227;o de reabilita&#231;&#227;o foram diferentes do ponto de vista estat&#237;stico. O maior escore m&#233;dio foi observado durante o exerc&#237;cio em esteira, ratificando as caracter&#237;sticas da popula&#231;&#227;o selecionada que, para inclus&#227;o no estudo, deveria ter hipocapta&#231;&#227;o transit&#243;ria em cintilografia associada ao teste ergom&#233;trico convencional. Entretanto, durante a sess&#227;o de reabilita&#231;&#227;o, a m&#233;dia dos escores da cintilografia foram maiores, com signific&#226;ncia estat&#237;stica, do que no repouso, indicando a presen&#231;a de poss&#237;vel isquemia mioc&#225;rdica induzida pelo exerc&#237;cio prescrito (p&lt;0,001). Entretanto, o valor m&#233;dio observado nessa situa&#231;&#227;o (15,07), menor do que o escore m&#233;dio de 19,3, observado durante o teste ergom&#233;trico convencional (p&lt;0,0001), indicou que o grau de hipocapta&#231;&#227;o durante a sess&#227;o de reabilita&#231;&#227;o foi menor.</p>
    <p>Pela an&#225;lise individual dos pacientes, pode-se notar que durante a sess&#227;o de reabilita&#231;&#227;o, 12 pacientes (46,2%) apresentaram o mesmo escore obtido no repouso, indicando que esses n&#227;o apresentavam prov&#225;vel isquemia mioc&#225;rdica induzida pelo exerc&#237;cio prescrito. Em 11 (42,3%), o escore obtido no exerc&#237;cio em bicicleta foi maior do que o escore do repouso, mas menor do que o escore observado no teste em esteira, indicando prov&#225;vel isquemia mioc&#225;rdica induzida pelo exerc&#237;cio prescrito, mas de menor grau do que aquela do teste convencional. Um total de tr&#234;s pacientes (11,5%) teve o mesmo escore nas duas cintilografias de esfor&#231;o, o que indica que esses pacientes tiveram, em ambas as situa&#231;&#245;es, o mesmo grau de isquemia mioc&#225;rdica.</p>
    <p>Considerando todos os casos com escore maior na cintilografia de bicicleta durante sess&#227;o de reabilita&#231;&#227;o do que no repouso, 14 casos (53,8%) apresentaram prov&#225;vel isquemia e 12 (46,6%) n&#227;o. No presente estudo, o eletrocardiograma, monitorizado pelo sistema Holter, n&#227;o foi capaz de identificar nenhum dos 14 casos com hipocapta&#231;&#227;o transit&#243;ria durante a reabilita&#231;&#227;o, se considerar-se o crit&#233;rio de um mil&#237;metro de depress&#227;o como indicativo de resposta isqu&#234;mica. Contudo, depress&#227;o ou depress&#227;o adicional, igual ou maior do que 0,5 mm ocorreu em tr&#234;s casos (sensibilidade de 21,4%). Deve ser lembrado que todos esses pacientes estavam em uso de medica&#231;&#227;o para tratamento de insufici&#234;ncia coron&#225;ria e a medica&#231;&#227;o em uso pode ter sido a causa da n&#227;o exist&#234;ncia de manifesta&#231;&#245;es isqu&#234;micas ao eletrocardiograma.</p>
    <p>Com efeito, entre os 12 pacientes sem isquemia durante a sess&#227;o de reabilita&#231;&#227;o, apenas dois (16,6%) n&#227;o tomavam antianginosos e 10 (83,4 %) usavam betabloqueadores e ou vasodilatadores. No grupo de 16 pacientes com isquemia, cinco (35%) n&#227;o tomavam antianginosos e nove (64,2%) utilizavam betabloqueadores e/ou vasodilatadores. Outra possibilidade para a discord&#226;ncia entre os resultados da cintilografia e do eletrocardiograma s&#227;o os fen&#244;menos do "aquecimento"<sup>18</sup> e do pr&#233;-condicionamento isqu&#234;mico<sup>19,20</sup>.</p>
    <p>Kay e cols.<sup>18</sup> demonstraram que exerc&#237;cios pr&#233;vios de baixa intensidade podem reduzir posteriores manifesta&#231;&#245;es isqu&#234;micas, quando exerc&#237;cios mais intensos s&#227;o realizados, em doentes com doen&#231;a arterial coron&#225;ria. Todos os pacientes da presente investiga&#231;&#227;o realizaram v&#225;rios exerc&#237;cios de aquecimento antes do exerc&#237;cio mais intenso realizado em bicicleta ergom&#233;trica. J&#225; o fen&#244;meno do pr&#233;-condicionamento isqu&#234;mico constitui-se numa resposta atenuada das manifesta&#231;&#245;es anginosas e eletrocardiogr&#225;ficas at&#233; duas horas depois de um exerc&#237;cio que provoque isquemia mioc&#225;rdica. Entretanto, ap&#243;s 24 horas do desencadeamento da isquemia, do exerc&#237;cio pr&#233;vio, h&#225; uma segunda janela de prote&#231;&#227;o que pode durar at&#233; 72 horas<sup>20</sup>.</p>
    <p>Todos os pacientes do nosso trabalho j&#225; estavam, h&#225; pelo menos seis meses, em programa e realizavam pelo menos tr&#234;s sess&#245;es semanais de exerc&#237;cios f&#237;sicos. Se esse mecanismo ocorreu nos nossos pacientes, o pr&#233;-condicionamento pode ser um fen&#244;meno com manifesta&#231;&#227;o apenas eletrocardiogr&#225;fica, mas sem interfer&#234;ncia nos achados da perfus&#227;o mioc&#225;rdica detectada pela cintilografia. Bogaty e cols.<sup>21</sup>, realizando tr&#234;s testes ergom&#233;tricos sucessivos em 12 coronariopatas, encontraram atenua&#231;&#227;o significativa da depress&#227;o do segmento ST no terceiro teste, mas que n&#227;o foi acompanhada de concomitante redu&#231;&#227;o da hipoperfus&#227;o mioc&#225;rdica na cintilografia com t&#225;lio 201.</p>
    <p>Os achados da presente investiga&#231;&#227;o alertam para a necessidade de se obedecer &#224; regra de prescri&#231;&#227;o de exerc&#237;cios que determina a maior individualiza&#231;&#227;o poss&#237;vel. Todos os cuidados tomados n&#227;o foram capazes de evitar a isquemia mioc&#225;rdica, quando se empregou m&#233;todo mais sofisticado, como a cintilografia, para identific&#225;-la. N&#227;o se pode deixar de supor, contudo, que o fen&#244;meno isqu&#234;mico nas sess&#245;es de reabilita&#231;&#227;o n&#227;o tenha ocorrido na maioria dos doentes, nos quais j&#225; se documentou efeitos ben&#233;ficos inequ&#237;vocos. Assim sendo, esse grau de isquemia aqui documentado pode, qui&#231;&#225;, ser est&#237;mulo para que as a&#231;&#245;es ben&#233;ficas se manifestem. Os resultados obtidos n&#227;o determinam uma mudan&#231;a de conduta na avalia&#231;&#227;o de coronariopatas em reabilita&#231;&#227;o. N&#227;o se pode, a partir deles, recomendar o emprego rotineiro da cintilografia mioc&#225;rdica para avaliar a acur&#225;cia da prescri&#231;&#227;o nos programas de reabilita&#231;&#227;o. Entretanto, o presente estudo abre a possibilidade de se utilizar a medicina nuclear na avalia&#231;&#227;o do grau de isquemia produzida por exerc&#237;cios regulares de reabilita&#231;&#227;o, em alguns pacientes especiais.</p>
    <p>Nossa investiga&#231;&#227;o &#233; limitada pelo pequeno n&#250;mero de pacientes inclu&#237;dos, por n&#227;o contemplar o sexo feminino e por n&#227;o terem sido relatados os eventuais desfechos cl&#237;nicos dos pacientes ao longo do tempo. N&#227;o se podem tamb&#233;m extrapolar os dados para as outras formas de prescri&#231;&#227;o do exerc&#237;cio, dentre elas a utiliza&#231;&#227;o do limiar anaer&#243;bico ventilat&#243;rio que se encontra em ascens&#227;o no pa&#237;s. Novas investiga&#231;&#245;es poder&#227;o esclarecer essas pend&#234;ncias.</p>
    <p>
      <bold>Conclus&#227;o</bold>
    </p>
    <p>Os resultados obtidos nesta investiga&#231;&#227;o permitem a elabora&#231;&#227;o das seguintes conclus&#245;es:</p>
    <p>1) A aplica&#231;&#227;o de exerc&#237;cios, prescritos com base na capacidade funcional &#250;til, pode produzir isquemia mioc&#225;rdica, em coronariopatas, durante sess&#227;o habitual de reabilita&#231;&#227;o supervisionada, identificada pela cintilografia mioc&#225;rdica com MIBI-Tc-99m.</p>
    <p>2) A monitoriza&#231;&#227;o eletrocardiogr&#225;fica, nas deriva&#231;&#245;es MC2 e MC5 do sistema Holter, n&#227;o foi capaz de identificar os pacientes com isquemia induzida pelo exerc&#237;cio prescrito, durante uma sess&#227;o habitual de reabilita&#231;&#227;o supervisionada, considerando-se como crit&#233;rio de positividade a presen&#231;a de depress&#227;o do segmento ST, igual ou maior do que 0,1 mV.</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>Este artigo &#233; parte da tese de doutorado de Romeu S. Meneghelo pela Faculdade de Medicina da Universidade de S&#227;o Paulo.</p>
    <p>
      <fn id="back" fn-type="corresp">
        <label>
          <bold>Correspond&#234;ncia:</bold>
        </label>
        <p> Romeu S&#233;rgio Meneghelo </p>
        <p> Rua Nicolau de Souza Queiroz, 194/161 </p>
        <p> Cep: 04105-000, S&#227;o Paulo - SP - Brasil </p>
        <p> E-mail: </p>
        <p><email xlink:href="rsmeneg@einstein.br">rsmeneg@einstein.br</email> / </p>
        <p>
          <email xlink:href="meneghelo@cardiol.br">meneghelo@cardiol.br</email>
        </p>
      </fn>
    </p>
    <p> Artigo enviado em 23/10/2007; revisado enviado em 29/01/2008; aceito em 01/02/2008.</p>
  </body>
  <back>
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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">Evaluation of prescription of exercise, for rehabilitation of coronary artery disease patients by myocardial scintigraphy</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>BACKGROUND: It is advisable that the intensity of the exercises for rehabilitation of patients with coronary artery disease does not cause myocardial ischemia. OBJECTIVE: Compare the capacity of myocardial tomographic scintigraphy with the electrocardiogram capacity in ischemia detection during rehabilitation session. METHODS: Twenty six patients with coronary artery disease, undergoing the rehabilitation program and with previous scintigraphy, with transient hypo-uptake have been administered a new injection of MIBI-Tc-99m during a training session when they were also monitored with dynamic electrocardiography. The rest scintigraphies, after ergometric treadmill test and rehabilitation session, were assessed in a semi-quantitative way using scores from 0 to 4 to classify each one of the chosen segments (0 = normal; 1 = discrete hypo-uptake; 2 = moderate; 3 = intense; 4 = lack of uptake). RESULTS: The means of the total scores found were: at rest = 12.9; after treadmill test = 19.3; after rehabilitation session = 15.1. There were statistically significant differences among them. An individual assessment showed that in 14 cases (53.8 %) hypo-uptake to some degree was identified during rehabilitation and in 12 cases (46.6%) it was not. Monitoring with the Holter system didn't show in any of the cases a ST segment depression equal or greater than 1mm. CONCLUSION: The exercises prescribed for patients with coronary artery disease, according to recommendations found in the literature, may trigger myocardial ischemia, assessed by scintigraphy during a rehabilitation session.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Coronary disease</kwd>
        <kwd>exercise therapy</kwd>
        <kwd>radionuclide imaging</kwd>
        <kwd>Technetium</kwd>
        <kwd>myocardial ischemia</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ORIGINAL ARTICLE</bold>
      </p>
      <p>
        <fn id="top-body2">
          <label>
            <bold>Evaluation of prescription of exercise, for rehabilitation of coronary artery disease patients by myocardial scintigraphy</bold>
          </label>
          <p>
            <bold>Romeu S. Meneghelo; H&#233;lio M. Magalh&#227;es; Paola E. P. Smanio; Angela R. C. N. Fuchs; Almir S. Ferraz; Rica D. D. Buchler; Susimeire Buglia; Luiz E. Mastrocolla; Anneliese F. Thom</bold>
          </p>
        </fn>
      </p>
      <p>Instituto Dante Pazzanese de Cardiologia, S&#227;o Paulo, SP - Brazil</p>
      <p>Mailing address</p>
      <p>
        <bold>SUMMARY</bold>
      </p>
      <p><bold>BACKGROUND:</bold> It is advisable that the intensity of the exercises for rehabilitation of patients with coronary artery disease does not cause myocardial ischemia.</p>
      <p><bold>OBJECTIVE:</bold> Compare the capacity of myocardial tomographic scintigraphy with the electrocardiogram capacity in ischemia detection during rehabilitation session.</p>
      <p><bold>METHODS:</bold> Twenty six patients with coronary artery disease, undergoing the rehabilitation program and with previous scintigraphy, with transient hypo-uptake have been administered a new injection of MIBI-Tc-99m during a training session when they were also monitored with dynamic electrocardiography. The rest scintigraphies, after ergometric treadmill test and rehabilitation session, were assessed in a semi-quantitative way using scores from 0 to 4 to classify each one of the chosen segments (0 = normal; 1 = discrete hypo-uptake; 2 = moderate; 3 = intense; 4 = lack of uptake).</p>
      <p><bold>RESULTS:</bold> The means of the total scores found were: at rest = 12.9; after treadmill test = 19.3; after rehabilitation session = 15.1. There were statistically significant differences among them. An individual assessment showed that in 14 cases (53.8 %) hypo-uptake to some degree was identified during rehabilitation and in 12 cases (46.6%) it was not. Monitoring with the Holter system didn't show in any of the cases a ST segment depression equal or greater than 1mm.</p>
      <p><bold>CONCLUSION:</bold> The exercises prescribed for patients with coronary artery disease, according to recommendations found in the literature, may trigger myocardial ischemia, assessed by scintigraphy during a rehabilitation session.</p>
      <p><bold>Key words:</bold> Coronary disease/rehabilitation; exercise therapy / methods; radionuclide imaging; Technetium, myocardial ischemia.</p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p>The concept of cardiovascular rehabilitation is currently confounded with that of secondary prevention, especially in the case of coronary arterial disease<sup>1</sup>. However, physical exercise is the basic foundation of programs and, alone, is able to promote benefits such as symptom minimization or extinction<sup>2,3</sup>, and the peripheral adaptations<sup>4-6</sup> which determine increase in the physical capacity<sup>7-10</sup> capable of reducing the ischemic manifestations to sub maximum charges. It also has an important role as aid in the fight against diabetes risk factors, sedentariness, hypertension, dyslipidemia and obesity. In spite of the unquestionable benefits, to exercise patients with coronary heart disease can be potentially harmful. Acute coronary events can cause sudden death, despite their low incidence<sup>11</sup>. The prescription of exercises that cause long periods of myocardial ischemia can be the foundation for triggering ventricular fibrillation and could, in the long term, cause myocardial necrosis<sup>12</sup>, considering trials carried out with animals<sup>13,14</sup>. Thus, the intensity of the prescribed exercises must remain below the intensity capable of causing myocardial ischemia, which is generally assessed through symptoms or ST segment depression. Such proposition is recommended by current guidelines<sup>15</sup>. Our option, among the several ways of prescribing these exercises, is to restrict them to the useful functional capacity<sup>16</sup>, which is the maximum effort level with absence of symptoms or clinical, electrocardiographic and hemodynamic changes. In patients without these changes, the Borg scale<sup>17</sup> between 13 and 15 is used, corresponding to the subjective sensation of somewhat hard - steady pace to hard. The greater sensitivity of the myocardial perfusion scintigraphy for diagnosing myocardial ischemia, as related to the occurrence of angina and to the ST segment depression, spurred the interest in studying the safety level of that prescription. The objective of this study is to compare the capacity of myocardial tomographic scintigraphy with the electrocardiogram capacity in ischemia detection during a rehabilitation session. The study was approved by the ethical committee of the institution.</p>
      <p>
        <bold>Case Report</bold>
      </p>
      <p>
        <bold>Study population</bold>
      </p>
      <p>Out of the 143 patients participating in the supervised rehabilitation program in our institution, 39 were selected presenting: period of permanence in the program higher than six months; diagnosis of coronary arterial disease made through previous cinecoronary arteriography with at least one obstructive lesion, equal or greater than 70%, ST segment depression in one of the main coronary arteries, triggered by effort of at least one millimeter in ergometric test done within one year before; lack of obstruction of the left branch and of pre-excitation to 12-derivation electrocardiogram. After signature of the respective informed consents, a myocardial scintigraphy was conducted with MIBI-Tc-99m, associated with ergometric treadmill test according to Bruce protocol. After a period not greater than a week, a rest scintigraphy was conducted. The cases presenting scintigraphic study compatible with transient myocardial ischemia in at least one segment of the left ventricle, were selected through visual assessment. In this initial scintigraphic analysis, 13 cases were excluded, where transient evident ischemia induced by exercise could not be diagnosed. Thus, the other 26 patients between 49 and 81 years of age (mean = 63,2 years) continued in the trial. A total of 13 patients (50%) were submitted to revascularization surgery. Myocardial infarction had occurred in 10 patients (38.5%), not submitted to subsequent surgery or angioplasty. An angioplasty during acute phase of myocardial infarction was conducted in two patients (7.7%) and elective angioplasty in one patient (3.8%). Among the 10 patients not submitted to revascularization, five (50%) had lesions in one artery, one (10%) in two arteries, and four (40%) in three vessels. The cinecoronary arteriography, before the revascularization, in the other 16 patients, showed that two (12.5 %) had lesions in one artery, eight (50%) in two arteries, and six (37.5 %) in three arteries.</p>
      <p>
        <bold>Methods</bold>
      </p>
      <p>All patients, after the initial scintigraphies, were connected to a dynamic ECG recorder, before the beginning of the rehabilitation session, in order to obtain a new scintigraphy associated with the prescribed exercise. The recording, in Cardios&#174; cassette tape recorder, in the MC2 and MC5 derivations covered all session. Before the stage known as continuous aerobics, done during 20 minutes in an ergometric bicycle with a prescribed charge, a peripheral vessel of one of the upper limbs was catheterized. On the next to last minute of the exercise the MIBI-Tc-99m dose was administered and the event button was activated in order to precisely evaluate the electrocardiographic tracing of the moment. Around one hour later, a new stress scintigraphy was obtained. ECG tracings of five and ten seconds, in the beginning of recording and when MIBI-Tc-99m was injected, were identified and printed in paper for visual analysis of the ST segment in successive complexes, with stable baseline.</p>
      <p>
        <bold>Bicycle ergometric test for exercise prescription</bold>
      </p>
      <p>A previous test for exercise prescription, limited sign and/or symptom, and during use of the medication was previously conducted in mechanical ergometric bicycle, with initial charge of 25 watts and 25-watts increments at every five minutes, The rehabilitation exercise prescription was based on cardiac rate and frequency at the end of the test immediately previous to the stage that caused symptoms, and hemodynamic or electrocardiographic changes. In individuals not presenting symptoms or any clinical and electrocardiographic changes, the cardiac rate and frequency were those when the patient showed stress perception level, between 13 and 15 of the Borg scale, that is, somewhat hard - steady pace to hard.</p>
      <p>
        <bold>Myocardial scintigraphy</bold>
      </p>
      <p>Myocardial perfusion scintigraphies were conducted through Single-Photon Emission Computed Tomography (SPECT), using as perfusion marker 2-Methoxyisobutylisonitrile marked with Technetium-99m (MIBI Tc 99m).</p>
      <p>The scintigraphies interpretations were done by consensus of the two observers, using a score system for each of the 20 segments of the four tomographic sections, chosen as follows: section of the minor apical axis, section of the minor medial axis, section of the minor basal axis, medial section of the vertical major axis. The highest intensity segment of radioactivity uptake, for each section, of each scintigraphy, was chosen as a reference. To this segment a value 0 (zero) was given. The adjacent segments of the same section received scores according to the following criteria:</p>
      <p>&#149; 0 = if they presented the same radioactivity reception intensity;</p>
      <p>&#149; 1 = if they showed a discrete hypo-uptake;</p>
      <p>&#149; 2 = if they showed moderate hypo-uptake;</p>
      <p>&#149; 3 = if they showed an intense hypo-uptake; and</p>
      <p>&#149; 4 = in the absence of uptake.</p>
      <p>The total of scores given to each segment of the four chosen sections was defined as the score of each scintigraphy, two of stress and one at rest. With this method, the scores of stress and at rest being equal indicate the absence of hypo-uptake induced by stress, and consequently the absence of ischemia induced by stress. If the score at stress is greater than at rest, this indicates the presence of hypo-uptake induced by stress, and consequently, ischemia induced by stress.</p>
      <p>
        <bold>Supervised rehabilitation session</bold>
      </p>
      <p>The rehabilitation session when the MIBI-Tc-99m dose was administered for a second stress scintigraphy was similar to all the sessions undergone by the patients, and was thus composed:</p>
      <p><bold>a)</bold> Warming: walking at normal pace for five minutes;</p>
      <p><bold>b)</bold> Aerobic stage with active pause: two to three minutes walks, interspersed by small races of one to two minutes, for 15 minutes;</p>
      <p><bold>c)</bold> Continuous aerobic stage: exercise in mechanical ergometric bicycle with applied charge, according to prescription based on the useful functional capacity, for 20 minutes;</p>
      <p><bold>d)</bold> Localized resistance exercises and stretching for 20 minutes.</p>
      <p>
        <bold>Statistical analysis</bold>
      </p>
      <p>The variables referring to ergometric tests in treadmill and bicycle, the prescribed charge and corresponding heart rate, the heart rate at the beginning of monitoring by the Holter system, and the heart rate during injection were summarized as means and standard deviations. The comparison between the prescribed heart rate and the observed heart rate when injecting MIBI-Tc-99m was made by paired Student's t test. The scores obtained in the rest scintigraphy, after treadmill ergometric test and during the rehabilitation session were presented as means and 95% confidence intervals (CI95%). The comparisons between the scores in the three situations were made with the analysis of variance technique (ANOVA) with repeated measurements. To localize the differences, the Bonferroni method for multiple comparisons was used.</p>
      <p>
        <bold>Results</bold>
      </p>
      <p>
        <bold>Treadmill ergometric test for obtaining myocardial scintigraphy</bold>
      </p>
      <p>The average exercise time on Bruce protocol was 7.4 minutes (SD=2.1). The heart rate mean varied from 73.6 bpm at rest to 137.1 bpm (SD=18.5) at stress peak. The blood pressure mean at rest was 141.3 (SD=21.3) / 83.4 (SD=8.9) mmHg, reaching 197.3 (SD=32)/82.6 (SD=7.2) mmHg at stress peak (<xref ref-type="table" rid="en_07t1-body2">tab. 1</xref>). All patients presented ST segment depression triggered by stress, but seven (27%) showed depression between 0.5 and 1mm. In 19 cases (73%) the depression was equal or higher than 1 mm. The mean value of the depression was 1.31 mm (SD = 0,74). Angina pectoris was the cause for exercise discontinuation in four patients (15.3%) and exhaustion in the others 22 (84,7%).</p>
      <p content-type="asset">
        <table-wrap id="en_07t1-body2">
          <graphic xlink:href="1678-4170-abc-91-04-0245-00007-gt01-en.jpg"/></table-wrap>
      </p>
      <p>
        <bold>Bicycle ergometric test for exercise prescription.</bold>
      </p>
      <p>The maximum average charge attained was 76 watts (SD = 14.9). The cardiac frequency mean varied from 71.3 bpm (SD = 12.8) at rest to 111.7 bpm (SD=22.9) at stress peak. Mean values of blood pressure varied from 129.8 (SD=17.5)/75.5 (SD = 10.1) (mmHg) on previous controls to 183.6 (SD = 22.5)/85.4 mmHg (SD = 15.4) at stress peak (<xref ref-type="table" rid="en_07t1-body2">tab. 1</xref>).</p>
      <p>
        <bold>Results of prescription based on useful functional capacity</bold>
      </p>
      <p>The average charge was 49 watts (SD = 8.6). The mean cardiac frequency for training was 104.7 bpm (SD = 15,7) representing, also in average, 66.7% (SD = 9.4) of the theoretical maximum cardiac frequency for the age (<xref ref-type="table" rid="en_07t1-body2">tab. 1</xref>).</p>
      <p>
        <bold>Dynamic electrocardiographic monitoring</bold>
      </p>
      <p>ST segment depression less than one millimeter or additional depression also less than one millimeter occurred in three cases only (11.5%) when MIBI-Tc-99m was injected during rehabilitation session. No patient had depression equal or greater than one millimeter. The mean cardiac frequency at rest was 82.7 bpm (SD = 14.3) and on injection was 102.6 bpm (SD = 15.1). There was no statistically significant difference between the cardiac frequency observed during injection of MIBI-Tc-99m, and the prescribed cardiac frequency for this moment with a mean of 104.7 (SD = 15.6). (P = 0.45).</p>
      <p>
        <bold>Myocardial scintigraphies</bold>
      </p>
      <p><xref ref-type="table" rid="tab2-body2">Table 2</xref> shows the score values obtained with the interpretation of the scintigraphies images at rest, at stress in treadmill and when exercising in ergometric bicycle, during rehabilitation session. The mean of the scores observed at rest was 12.9 (SD = 9.1), at stress in treadmill was 19.3 (DP = 10), and during rehabilitation was 15.1 (SD = 10.2).</p>
      <table-wrap id="tab2-body2">
        <graphic xlink:href="1678-4170-abc-91-04-0245-00007-gt02-en.jpg"/></table-wrap>
      <p>The mean difference between score at rest and score of scintigraphy associated with treadmill test was 6.3 CI (95%) [4.3; 8.3] (P&lt;0.0001), and between the score at rest and the score of the scintigraphy executed during the rehabilitation session was 2.2 CI (95%) [0.8; 3.6] (P&lt;0.001). The mean difference between the score of the scintigraphy executed during the rehabilitation session and the score of scintigraphy associated with treadmill test was 4.1 CI (95%) [2.3; 5.8] (P&lt;0.0001). Analyzed alone, all the cases presented a higher score in the stress scintigraphy in treadmill than at rest, as this condition was determinant for inclusion of the case in the trial. However, during the rehabilitation session, 12 patients (46.2%) had the same score obtained at rest. In 11 (42.3%), the score obtained in the bicycle exercise was higher than the score at rest, but less than the score at the treadmill test. A total of three patients (11.5%) had the same score in the two tests. Thus, in 14 cases (53.8%), the score observed in the scintigraphy during rehabilitation session was higher than that obtained at rest, indicating the presence of transient hypo-uptake during the rehabilitation session. Suggestive myocardial ischemia has not occurred in 12 cases (46.6%), which presented the same score in myocardial scintigraphy during the rehabilitation session and at rest.</p>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>Current guidelines determine that the prescription of exercise for patients with coronary heart disease must be made at levels that do not produce myocardial ischemia characterized by angina pectoris and/or ST segment depression<sup>15</sup>. The observance of this rule can be easily done today through clinical and electrocardiographic monitoring in a rehabilitation session. However, under conditions such as: after acute myocardial infarction, ventricular hypertrophies, previous changes of the ST segment and others, the myocardial perfusion scintigraphy allow the precise evaluation of possible myocardial ischemia presence during cardiovascular rehabilitation. In this sense, the present investigation is original and extends the possible use of nuclear cardiology.</p>
      <p>The patients selected for the investigation did not constitute a homogeneous group as to clinical conditions at the time of inclusion, but all of them presented coronary heart disease, identified through coronary angiography and, thus, justifying to present myocardial scintigraphy with hypo-uptake induced by stress. A total of 10 patients (38.5%) was not submitted to any kind of revascularization, and the remaining 16 (61.5%) were revascularized through surgery and/or angioplasty. Although, through clinical history, in 13 an episode of myocardial infarction was clearly identified, in 23 a score higher than zero was recognized in rest scintigraphy, showing that only three had not had previous myocardial infarction. Such characteristics make the group similar to the groups in rehabilitation, according to current indications for supervised rehabilitation.</p>
      <p>To select the protocol used, we tried to change as little as possible the rehabilitation session so that the results would not suffer the interference of complex procedures likely to generate insecurity and anxiety in the patients. Unlike a usual session, a Holter recorder was installed, and a peripheral vessel catheterization was conducted at the beginning of the exercise with bicycle only. Also, the session environment should not present characteristics of a great trial. However, we cannot discard the hypothesis that some degree of anxiety may have interfered with the results.</p>
      <p>The characteristics of the bicycle test for exercise prescription, used by our institution, and also in this investigation, have the scope of identifying cardiac frequency values and electrocardiographic changes, as close as possible to the stable state at a given charge. The errors made are thus minimized when the prescription is done from a test shorter than five minutes in each stage, used by the majority of conventional protocols. The mean advised values of cardiac frequency of 104.7 (SD 15.6) and the mean observed values at the 19<sup>th</sup> minute of exercise in bicycle during rehabilitation session of 102.6 (SD=15.1) were not different from the statistical viewpoint (p&lt;0.005). Such data show the good accuracy of the prescription test to foresee the cardiac frequency values after 20 minutes of stress, with a prescribed charge for the same ergometer, in both situations.</p>
      <p>The mean values of the prescribed charge of 49 watts (SD = 8.6) and cardiac frequency of 104.7 (SD = 15.6), corresponding to an average percentage of maximum cardiac frequency of 66.7% (SD = 9.4), are relatively modest for the normal individual training, but perfectly acceptable for the rehabilitation of patients with coronary heart disease, according to the prescription levels recommended by guidelines in use<sup>15</sup>.</p>
      <p>The use of electrocardiographic monitoring in the present trial enabled in a simple and accurate way, obtaining the cardiac frequency and the ST segment evaluation during injection of MIBI-Tc-99m. The system used allowed a good correlation between these two variables, given that, at the time of the injection, an event button was activated, recording an electronic signal concurrent with the electrocardiographic tracing of that moment.</p>
      <p>The mean scores observed in scintigraphies at rest, in treadmill and bicycle during the rehabilitation session were different from the statistical viewpoint. The higher mean score was observed during the treadmill exercise, confirming the characteristics of the selected population which, for inclusion in the trial, should have transient hypo-uptake in scintigraphy associated with the conventional ergometric test. However, during the rehabilitation session, the mean scintigraphy scores were higher, with statistic relevance than at rest, indicating the presence of possible myocardial ischemia induced by the prescribed exercise (p&lt;0.001). However, the mean value observed in that situation (15.07), less than the mean score of 19.3 observed during ergometric conventional test (p&lt;0.0001), indicated that the hypo-uptake degree during the rehabilitation session was smaller.</p>
      <p>Through individual evaluation of the patients it was possible to observe that during the rehabilitation session, 12 patients (46.2%) showed the same score obtained at rest, indicating that they did not present probable myocardial ischemia induced by the prescribed exercise. In 11 patients (42.3%), the score at the bicycle exercise was higher than the score at rest, but smaller than the score observed in the treadmill test, indicating probable myocardial ischemia induced by the prescribed exercise, but of a lesser degree than the one observed in a conventional test. A total of three patients (11.5%) had the same score in both stress scintigraphies, indicating that those patients had, in both situations, the same degree of myocardial ischemia.</p>
      <p>Considering all the cases with a score in the bicycle scintigraphy during the rehabilitation session higher than at rest, 14 cases (53.8%) presented probable ischemia and 12 (46.6%) did not. In this trial, the electrocardiogram monitored by the Holter system was unable to identify any of the 14 cases with transient hypo-uptake during rehabilitation, if the criteria of one millimeter depression are to be considered as indicative of ischemic answer. However, depression or additional depression equal or higher than 0.5 mm occurred in three cases (sensitivity of 21.4%). It must be noted that all these patients were using medication for coronary failure, and the medication in use may be the cause of absence of ischemic manifestations at the electrocardiogram.</p>
      <p>Indeed, among the 12 patients without ischemia during the rehabilitation session, only two (16.6%) didn't take antianginal agents, and 10 (83.4%) used beta blockers and/or vasodilators. In the group of 16 patients with ischemia, five (35%) didn't take antianginal agents and nine (64.2%) used beta blockers and/or vasodilators. Another possibility for the discrepancy between the results of the scintigraphy and electrocardiogram were the "warming"<sup>18</sup> and ischemic preconditioning<sup>19,20</sup> phenomenons.</p>
      <p>Kay e cols.<sup>18</sup> showed that previous low intensity exercises can reduce posterior ischemic manifestations, when more intense exercises are made, in patients with coronary arterial disease. All the patients of this investigation have done several warming exercises before the more intense exercises done in ergometric bicycle. On the other hand, the ischemic preconditioning phenomenon was an attenuated response of the anginal and electrocardiographic manifestations, up to two hours after an exercise that caused myocardial ischemia. However, after 24 hours of the ischemia setting in from the previous exercise, there is a second protection window that can last up to 72 hours<sup>20</sup>.</p>
      <p>All our trial patients were, at least for six months, in a program and had at least three weekly sessions of physical exercises. If this mechanism occurred with our patients, the preconditioning can be a phenomenon with electrocardiographic manifestation only, but which does not interfere with the findings of myocardial perfusion detected by scintigraphy. Bogaty et al<sup>21</sup>, doing three successive ergometric tests in 12 patients with coronary heart disease, found significant attenuation of the ST segment depression during the third test, which was not followed by concurrent reduction of myocardial hypo perfusion in scintigraphy with thallium 201.</p>
      <p>The findings of the present investigation alert to the need of obeying the rule of exercise prescription determining the greatest individualization possible. All care taken could not avoid myocardial ischemia when a more sophisticated method, such as scintigraphy, was used to identify it. However, we cannot but presume, that the ischemic phenomenon during the rehabilitation sessions has not occurred in the majority of the patients, in whom unequivocal benefic effects have already been documented. Therefore, such degree of ischemia as documented here can perhaps be a stimulant for the manifestation of beneficial actions. The results obtained do not determine a change in behavior when evaluating patients with coronary heart disease in rehabilitation. Based on them, we cannot recommend the routine use of myocardial scintigraphy to evaluate the accuracy of the prescription in rehabilitation programs. However, the present study opens the possibility of using nuclear medicine in evaluating the degree of ischemia produced by regular rehabilitation exercises in some special patients.</p>
      <p>Our trial is limited by the small number of patients included, for not considering the female gender, and because the possible clinical outcomes on the long run have not been reported. Neither can we extrapolate the data to other types of exercise prescription, among which the use of ventilatory anaerobic threshold that is on the rise in the country. New investigations can clarify these matters.</p>
      <p>
        <bold>Conclusion</bold>
      </p>
      <p>The results obtained in this investigation allow drawing the following conclusions:</p>
      <p><bold>1)</bold> The use of exercises, prescribed based on the useful functional capacity, may cause myocardial ischemia in patients with coronary heart disease, during a usual session of supervised rehabilitation, identified by myocardial scintigraphy with MIBI-Tc-99m.</p>
      <p><bold>2)</bold> The electrocardiographic monitoring, with Holter system MC2 and MC5 derivations, was unable to identify patients with ischemia induced by the prescribed exercise, during a usual session of supervised rehabilitation, considering the presence of ST segment depression equal or higher than 0.1 mV as positivity criteria.</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 article is part of the thesis of Doctoral submitted by Romeu S. Meneghelo, from Faculdade de Medicina da Universidade de S&#227;o Paulo.</p>
      <p>
        <bold>References</bold>
      </p>
    </body>
  </sub-article>
</article>
