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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">sh3wDYztZMs7YHxR6RQRQDd</article-id>
      <article-id pub-id-type="other">00002</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2008000300002</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(08)09000302</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2008000300002</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Preval&#234;ncia e preditores da resposta cardioinibit&#243;ria &#224; massagem do seio carot&#237;deo em 502 pacientes ambulatoriais</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Lacerda</surname>
            <given-names>Gustavo de Castro</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pedrosa</surname>
            <given-names>Roberto Coury</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lacerda</surname>
            <given-names>Renato C&#244;rtes de</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Santos</surname>
            <given-names>Marcela Cedenilla dos</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Perez</surname>
            <given-names>Maur&#237;cio de Andrade</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Teixeira</surname>
            <given-names>Alfredo Brasil</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Siqueira-Filho</surname>
            <given-names>Aristarco Gon&#231;alves de</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="state">Rio de Janeiro</named-content>
        </addr-line>
        <institution content-type="orgname">Universidade Federal do Rio de Janeiro</institution>
        <country country="BR">Brazil</country>
      </aff>
      <aff id="aff02">
        <addr-line>
          <named-content content-type="city">Rio de Janeiro</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <institution content-type="orgname">Hospital Geral de Bonsucesso</institution>
        <country country="BR">Brasil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>03</month>
        <year>2008</year>
      </pub-date>
      <volume>90</volume>
      <issue>3</issue>
      <fpage>163</fpage>
      <lpage>171</lpage>
      <history>
        <date date-type="accepted">
          <day>08</day>
          <month>08</month>
          <year>2007</year>
        </date>
        <date date-type="rev-recd">
          <day>20</day>
          <month>06</month>
          <year>2007</year>
        </date>
        <date date-type="received">
          <day>22</day>
          <month>04</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: A resposta cardioinibit&#243;ria (RCI) caracteriza-se por assistolia &gt; 3 segundos em resposta a 5 a 10 segundos de massagem do seio carot&#237;deo (MSC). O implante de marcapasso &#233; indicado nos pacientes com s&#237;ncope inexplicada e RCI. OBJETIVO: Determinar a preval&#234;ncia e os preditores da RCI em pacientes com alta preval&#234;ncia de doen&#231;a cardiovascular. Avaliar o significado cl&#237;nico da RCI em pacientes com hist&#243;ria de s&#237;ncope ou queda. M&#201;TODOS: Desenho transversal. Casu&#237;stica: pacientes ambulatoriais, com idade &gt; 50 anos, encaminhados ao Setor de Eletrocardiografia de um hospital terci&#225;rio. Indiv&#237;duos com dem&#234;ncia, sopro carot&#237;deo, hist&#243;ria de infarto agudo do mioc&#225;rdio ou acidente vascular cerebral nos &#250;ltimos tr&#234;s meses foram exclu&#237;dos. Os pacientes foram submetidos a MSC direito por 10 segundos seguida de MSC esquerdo por 10 segundos. As MSCs foram realizadas na posi&#231;&#227;o supina por um &#250;nico investigador. RESULTADOS: No total, 502 indiv&#237;duos foram submetidos a MSC, dos quais 52 apresentaram RCI (preval&#234;ncia: 10,4%; intervalo de confian&#231;a de 95% [IC95%]: 7,7%-13%). Os preditores independentes da RCI foram: sexo masculino ("odds ratio" [OR]: 2,61; IC95%: 1,3%-5,1%), cardiopatia estrutural (OR: 3,28; IC95%: 1,3%-7,9%), e freq&#252;&#234;ncia card&#237;aca de base (p &lt; 0,05). A sensibilidade da RCI no diagn&#243;stico etiol&#243;gico de epis&#243;dios de s&#237;ncope ou queda foi baixa (9,8%). Sua especificidade foi boa (89,5%), sendo melhor nas mulheres (95,3%) e nos n&#227;o-cardiopatas (96,2%). CONCLUS&#195;O: A RCI foi encontrada em 10,4% dos pacientes com idade &gt; 50 anos. Nos homens e nos cardiopatas, a probabilidade de a MSC provocar o aparecimento de RCI foi maior. Nas mulheres e nos pacientes sem cardiopatia estrutural aparente, a RCI mostrou ser achado altamente espec&#237;fico para o diagn&#243;stico etiol&#243;gico dos epis&#243;dios de s&#237;ncope ou queda.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Seio carot&#237;deo</kwd>
        <kwd>s&#237;ncope</kwd>
        <kwd>arritmia</kwd>
        <kwd>pacientes ambulatoriais</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>04</day>
        <month>04</month>
        <year>2008</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>ARTIGO ORIGINAL</bold>
    </p>
    <p>
      <bold>Preval&#234;ncia e preditores da resposta cardioinibit&#243;ria &#224; massagem do seio carot&#237;deo em 502 pacientes ambulatoriais</bold>
    </p>
    <p>
      <bold>Gustavo de Castro Lacerda; Roberto Coury Pedrosa; Renato C&#244;rtes de Lacerda; Marcela Cedenilla dos Santos; Maur&#237;cio de Andrade Perez; Alfredo Brasil Teixeira; Aristarco Gon&#231;alves de Siqueira-Filho</bold>
    </p>
    <p>Universidade Federal do Rio de Janeiro - Hospital Geral de Bonsucesso - Rio de Janeiro, RJ - Brasil</p>
    <p>
      <xref ref-type="corresp" rid="back">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>FUNDAMENTO: </bold> A resposta cardioinibit&#243;ria (RCI) caracteriza-se por assistolia <underline>&gt;</underline> 3 segundos em resposta a 5 a 10 segundos de massagem do seio carot&#237;deo (MSC). O implante de marcapasso &#233; indicado nos pacientes com s&#237;ncope inexplicada e RCI. </p>
    <p><bold>OBJETIVO: </bold> Determinar a preval&#234;ncia e os preditores da RCI em pacientes com alta preval&#234;ncia de doen&#231;a cardiovascular. Avaliar o significado cl&#237;nico da RCI em pacientes com hist&#243;ria de s&#237;ncope ou queda. </p>
    <p><bold>M&#201;TODOS:</bold> Desenho transversal. Casu&#237;stica: pacientes ambulatoriais, com idade <underline>&gt;</underline> 50 anos, encaminhados ao Setor de Eletrocardiografia de um hospital terci&#225;rio. Indiv&#237;duos com dem&#234;ncia, sopro carot&#237;deo, hist&#243;ria de infarto agudo do mioc&#225;rdio ou acidente vascular cerebral nos &#250;ltimos tr&#234;s meses foram exclu&#237;dos. Os pacientes foram submetidos a MSC direito por 10 segundos seguida de MSC esquerdo por 10 segundos. As MSCs foram realizadas na posi&#231;&#227;o supina por um &#250;nico investigador. </p>
    <p><bold>RESULTADOS: </bold> No total, 502 indiv&#237;duos foram submetidos a MSC, dos quais 52 apresentaram RCI (preval&#234;ncia: 10,4%; intervalo de confian&#231;a de 95% [IC95%]: 7,7%-13%). Os preditores independentes da RCI foram: sexo masculino ("odds ratio" [OR]: 2,61; IC95%: 1,3%-5,1%), cardiopatia estrutural (OR: 3,28; IC95%: 1,3%-7,9%), e freq&#252;&#234;ncia card&#237;aca de base (p &lt; 0,05). A sensibilidade da RCI no diagn&#243;stico etiol&#243;gico de epis&#243;dios de s&#237;ncope ou queda foi baixa (9,8%). Sua especificidade foi boa (89,5%), sendo melhor nas mulheres (95,3%) e nos n&#227;o-cardiopatas (96,2%). </p>
    <p><bold>CONCLUS&#195;O: </bold> A RCI foi encontrada em 10,4% dos pacientes com idade <underline>&gt;</underline> 50 anos. Nos homens e nos cardiopatas, a probabilidade de a MSC provocar o aparecimento de RCI foi maior. Nas mulheres e nos pacientes sem cardiopatia estrutural aparente, a RCI mostrou ser achado altamente espec&#237;fico para o diagn&#243;stico etiol&#243;gico dos epis&#243;dios de s&#237;ncope ou queda.</p>
    <p><bold>Palavras-chave: </bold> Seio carot&#237;deo, s&#237;ncope, arritmia, pacientes ambulatoriais.</p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p>A hipersensibilidade do seio carot&#237;deo (HSC) &#233; a exacerba&#231;&#227;o de um reflexo presente em indiv&#237;duos normais. A Sociedade Europ&#233;ia de Cardiologia definiu essa condi&#231;&#227;o como assistolia de pelo menos 3 segundos ou queda da press&#227;o arterial (PA) sist&#243;lica de pelo menos 50 mmHg, provocadas por 5 a 10 segundos de massagem do seio carot&#237;deo (MSC)<sup>1</sup>.</p>
    <p>Na maioria dos indiv&#237;duos a MSC provoca um pequeno grau de alentecimento da freq&#252;&#234;ncia card&#237;aca (FC), com discreta redu&#231;&#227;o dos n&#237;veis tensionais. Duas formas de resposta &#224; MSC s&#227;o consideradas patol&#243;gicas: a cardioinibit&#243;ria, caracterizada pela presen&#231;a de assistolia de pelo menos 3 segundos, e a vasodepressora, definida pela queda significativa da PA sist&#243;lica (<underline>&gt;</underline> 50 mmHg). Ambas podem ocorrer de forma isolada (respostas cardioinibit&#243;ria ou vasodepressora puras) ou combinadas (resposta mista)<sup>1,2</sup>.</p>
    <p>Ainda existem d&#250;vidas a respeito do significado cl&#237;nico da resposta cardioinibit&#243;ria<sup>3,4</sup>. A MSC pode provocar o aparecimento de assistolia <underline>&gt;</underline> 3 segundos em uma parcela significativa da popula&#231;&#227;o<sup>5,6</sup>. Esse comportamento ocorre mais freq&#252;entemente nos indiv&#237;duos com hist&#243;ria de s&#237;ncope, particularmente nos idosos e nos portadores de cardiopatia estrutural<sup>7,8,9</sup>.</p>
    <p>No Brasil, ainda n&#227;o foram publicados estudos que tenham avaliado a preval&#234;ncia da resposta cardioinibit&#243;ria &#224; MSC. Na literatura estrangeira, os preditores da resposta cardioinibit&#243;ria s&#227;o descritos em poucos trabalhos, em sua maioria com pequeno n&#250;mero de pacientes<sup>6,10</sup>.</p>
    <p>Este estudo tem o objetivo de determinar a preval&#234;ncia e os preditores da resposta cardioinibit&#243;ria &#224; MSC em pacientes ambulatoriais, com idade <underline>&gt;</underline> 50 anos e com alta preval&#234;ncia de doen&#231;a cardiovascular. Al&#233;m disso, neste estudo pretende-se avaliar o significado cl&#237;nico da resposta cardioinibit&#243;ria &#224; MSC em pacientes com hist&#243;ria de epis&#243;dios de s&#237;ncope ou queda no &#250;ltimo ano.</p>
    <p>
      <bold>M&#233;todos</bold>
    </p>
    <p><italic>Desenho -</italic> Estudo transversal realizado no Ambulat&#243;rio de Cardiologia do Hospital Geral de Bonsucesso (HGB), um hospital p&#250;blico de n&#237;vel terci&#225;rio. O recrutamento dos pacientes foi iniciado ap&#243;s a aprova&#231;&#227;o do estudo pelo Comit&#234; de &#201;tica em Pesquisa dessa institui&#231;&#227;o. Todos os pacientes assinaram termo de consentimento livre e esclarecido.</p>
    <p><italic>Casu&#237;stica -</italic> Selecionou-se, de modo aleat&#243;rio, pacientes ambulatoriais com idade <underline>&gt;</underline> 50 anos, encaminhados para registro eletrocardiogr&#225;fico precedendo consulta cardiol&#243;gica de rotina, e pacientes que por solicita&#231;&#227;o de m&#233;dicos de outras especialidades, cl&#237;nicas ou cir&#250;rgicas, foram encaminhados para realiza&#231;&#227;o do eletrocardiograma.</p>
    <p>Os indiv&#237;duos selecionados foram entrevistados pelo investigador principal deste estudo e submetidos a avalia&#231;&#227;o cl&#237;nica. Os pacientes foram esclarecidos acerca dos objetivos do estudo e dos riscos da MSC. Durante a anamnese, enfatizou-se a pesquisa de hist&#243;ria de epis&#243;dios de s&#237;ncope ou queda inexplicadas.</p>
    <p>S&#237;ncope foi definida como perda abrupta e transit&#243;ria da consci&#234;ncia, associada a perda do t&#244;nus postural.</p>
    <p>Considerou-se queda inexplicada toda situa&#231;&#227;o na qual o indiv&#237;duo &#233; levado a um n&#237;vel inferior ou ao ch&#227;o sem que situa&#231;&#245;es acidentais (trope&#231;o, empurr&#227;o) ou m&#233;dicas (crise convulsiva, acidente vascular cerebral, abuso de &#225;lcool, hipotens&#227;o ortost&#225;tica, arritmia) possam ser responsabilizadas. Pacientes com mais de tr&#234;s quedas no &#250;ltimo ano tamb&#233;m foram considerados portadores de queda inexplicada, ainda que apresentassem hist&#243;ria de causa acidental para esses epis&#243;dios.</p>
    <p>Foram exclu&#237;dos do estudo os pacientes que n&#227;o assinaram o termo de consentimento livre e esclarecido, e aqueles nos quais n&#227;o foi poss&#237;vel realizar a MSC (indiv&#237;duos com obesidade m&#243;rbida, feridas no pesco&#231;o e traqueostomizados). Os pacientes com dem&#234;ncia, os portadores de sopro carot&#237;deo ou com Doppler de car&#243;tidas documentando estenose carot&#237;dea <underline>&gt;</underline> 50%, os indiv&#237;duos com hist&#243;ria de infarto agudo do mioc&#225;rdio nos &#250;ltimos tr&#234;s meses ou com passado de acidente vascular cerebral ou ataque isqu&#234;mico transit&#243;rio nos &#250;ltimos tr&#234;s meses, os pacientes com bradiarritmia sintom&#225;tica, os portadores de marcapasso definitivo e aqueles com hist&#243;rico de arritmia ventricular complexa tamb&#233;m foram exclu&#237;dos.</p>
    <p><italic>T&#233;cnica de realiza&#231;&#227;o da MSC -</italic> A MSC foi realizada em ambiente com desfibrilador card&#237;aco, marcapasso transcut&#226;neo e com todo o material necess&#225;rio para realiza&#231;&#227;o de ressuscita&#231;&#227;o cardiopulmonar. Em todos os casos, o primeiro autor deste estudo foi o respons&#225;vel pela realiza&#231;&#227;o da MSC.</p>
    <p>A MSC foi realizada apenas na posi&#231;&#227;o supina, primeiramente do lado direito. Exerceu-se press&#227;o com movimentos longitudinais no ponto onde &#233; palpada a m&#225;xima impuls&#227;o do pulso carot&#237;deo, imediatamente acima da cartilagem tire&#243;ide e abaixo do &#226;ngulo da mand&#237;bula, por um per&#237;odo de 10 segundos. Nos casos sem complica&#231;&#227;o imediata, o procedimento foi repetido ap&#243;s um minuto do lado esquerdo. As altera&#231;&#245;es da FC e do ritmo card&#237;aco provocadas pela MSC foram registradas no eletrocardi&#243;grafo Cardiofax modelo 9010B<sup>&#174;</sup> a uma velocidade de 25 mm/s.</p>
    <p>Ap&#243;s o t&#233;rmino do procedimento, todos os indiv&#237;duos foram questionados sobre a presen&#231;a de sintomas durante a realiza&#231;&#227;o da MSC.</p>
    <p>O maior intervalo RR provocado pela MSC foi medido com aux&#237;lio de r&#233;gua, lupa e compasso, com precis&#227;o de 20 ms.</p>
    <p><italic>Desfecho -</italic> Resposta cardioinibit&#243;ria &#224; MSC. Foram considerados portadores de resposta cardioinibit&#243;ria todos os pacientes nos quais a MSC provocou o aparecimento de assistolia <underline>&gt;</underline> 3 segundos, independentemente do comportamento da PA e da presen&#231;a de sintomas.</p>
    <p><italic>An&#225;lise estat&#237;stica -</italic> Para estudar a preval&#234;ncia da resposta cardioinibit&#243;ria com seguran&#231;a de 95%, seria necess&#225;ria a realiza&#231;&#227;o da MSC em 427 indiv&#237;duos. Esse n&#250;mero foi obtido com base na estimativa de que a preval&#234;ncia da resposta cardioinibit&#243;ria nos pacientes com idade <underline>&gt;</underline> 50 anos atendidos no Ambulat&#243;rio de Cardiologia do HGB seja igual a 12% &#177; 3%, e de que o n&#250;mero de pacientes atendidos anualmente nesse ambulat&#243;rio seja igual a oito mil. Como tamb&#233;m tinha-se por objetivo estudar os preditores da resposta cardioinibit&#243;ria, optou-se por aumentar o tamanho dessa amostra, estudando aproximadamente 500 pacientes.</p>
    <p>As compara&#231;&#245;es entre o maior intervalo RR obtido durante a massagem do seio carot&#237;deo direito (MSCD) e a massagem do seio carot&#237;deo esquerdo (MSCE) da popula&#231;&#227;o geral, dos homens, das mulheres, dos usu&#225;rios e n&#227;o-usu&#225;rios de drogas cronotr&#243;picas negativas, dos portadores e n&#227;o-portadores de cardiopatia estrutural foram realizadas com aux&#237;lio do teste de Mann-Whitney.</p>
    <p>As vari&#225;veis dicot&#244;micas preditoras da presen&#231;a da resposta cardioinibit&#243;ria foram determinadas por meio da confec&#231;&#227;o de tabelas de conting&#234;ncia e da determina&#231;&#227;o das raz&#245;es de preval&#234;ncia. Estabeleceu-se o valor de p por meio do teste exato de Fisher. Foi considerada significativa toda a associa&#231;&#227;o com p &lt; 0,05. As vari&#225;veis cont&#237;nuas preditoras da presen&#231;a de resposta cardioinibit&#243;ria foram comparadas por meio do teste <italic>t</italic>. Vari&#225;veis com p &lt; 0,1 na an&#225;lise univariada foram inclu&#237;das em um modelo bin&#225;rio de regress&#227;o log&#237;stica (modelo <italic>stepwise forward Wald</italic>).</p>
    <p>
      <bold>Resultados</bold>
    </p>
    <p><italic>Descri&#231;&#227;o da popula&#231;&#227;o -</italic> Durante o per&#237;odo de recrutamento, 1.686 pacientes com idade <underline>&gt;</underline> 50 anos passaram pelo Setor de Eletrocardiografia do Ambulat&#243;rio do HGB. Desses pacientes, 562 (33,3%) foram selecionados de modo aleat&#243;rio, dos quais 60 foram exclu&#237;dos do estudo (<xref ref-type="fig" rid="f1">fig. 1</xref>). As caracter&#237;sticas dos 502 indiv&#237;duos submetidos a MSC est&#227;o apresentadas, de forma resumida, na <xref ref-type="table" rid="t1">tabela 1</xref>.</p>
    <p content-type="asset">
      <fig id="f1">
        <graphic xlink:href="1678-4170-abc-90-03-0163-00002-gf01.jpg"/></fig>
    </p>
    <p content-type="asset">
      <table-wrap id="t1">
        <graphic xlink:href="1678-4170-abc-90-03-0163-00002-gt01.jpg"/></table-wrap>
    </p>
    <p>O valor m&#233;dio do maior intervalo RR provocado pela MSCD foi superior ao valor m&#233;dio do maior intervalo RR provocado pela MSCE. Esse comportamento foi observado na popula&#231;&#227;o geral, nos homens, nas mulheres e em quatro grupos de pacientes (<xref ref-type="table" rid="t2">tab. 2</xref>). O valor m&#233;dio do maior intervalo RR provocado pela MSC nos homens foi superior &#224;quele verificado entre as mulheres (p &lt; 0,05). O valor m&#233;dio do maior intervalo RR provocado pela MSC nos usu&#225;rios de medica&#231;&#227;o cronotr&#243;pica negativa foi superior ao encontrado nos n&#227;o-usu&#225;rios de medica&#231;&#227;o cronotr&#243;pica negativa (p &lt; 0,05), e o valor m&#233;dio do maior intervalo RR provocado pela MSC nos portadores de cardiopatia estrutural foi superior &#224;quele encontrado nos n&#227;o-portadores de cardiopatia estrutural (p &lt; 0,05) (<xref ref-type="table" rid="t2">tab. 2</xref>).</p>
    <p content-type="asset">
      <table-wrap id="t2">
        <graphic xlink:href="1678-4170-abc-90-03-0163-00002-gt02.jpg"/></table-wrap>
    </p>
    <p><italic>Preval&#234;ncia e preditores da resposta cardioinibit&#243;ria &#224; MSC -</italic> A MSC provocou o aparecimento de resposta cardioinibit&#243;ria em 52 pacientes (preval&#234;ncia: 10,4%; intervalo de confian&#231;a de 95% [IC95%]: 7,7% a 13%). A resposta cardioinibit&#243;ria foi detectada em 34 indiv&#237;duos exclusivamente durante a MSCD, e em 9 apenas no momento da MSCE. Resposta cardioinibit&#243;ria durante a MSCD e durante a MSCE foi observada em 9 pacientes (<xref ref-type="fig" rid="f2">figs. 2</xref> e <xref ref-type="fig" rid="f3">3</xref>).</p>
    <p content-type="asset">
      <fig id="f2">
        <graphic xlink:href="1678-4170-abc-90-03-0163-00002-gf02.jpg"/></fig>
    </p>
    <p content-type="asset">
      <fig id="f3">
        <graphic xlink:href="1678-4170-abc-90-03-0163-00002-gf03.jpg"/></fig>
    </p>
    <p>As caracter&#237;sticas dos pacientes com resposta cardioinibit&#243;ria presente e ausente encontram-se descritas na <xref ref-type="table" rid="t1">tabela 1</xref>.</p>
    <p>Os portadores da resposta cardioinibit&#243;ria tinham FC de base inferior &#224; daqueles sem essa resposta (<xref ref-type="table" rid="t1">tab. 1</xref>, <xref ref-type="fig" rid="fig4">fig. 4</xref>).</p>
    <fig id="fig4">
      <graphic xlink:href="1678-4170-abc-90-03-0163-00002-gf04.jpg"/></fig>
    <p>N&#227;o se observou nenhuma rela&#231;&#227;o significativa entre hist&#243;ria de s&#237;ncope ou queda e presen&#231;a de resposta cardioinibit&#243;ria &#224; MSC. Na an&#225;lise univariada, o sexo masculino (RR: 2,82; p &lt; 0,05) e a presen&#231;a de coronariopatia conhecida (RR: 2,49; p &lt; 0,05) e de cardiopatia estrutural (RR: 3,42; p &lt; 0,05) foram os maiores preditores da presen&#231;a de resposta cardioinibit&#243;ria &#224; MSC (<xref ref-type="fig" rid="f5">fig. 5</xref>).</p>
    <p content-type="asset">
      <fig id="f5">
        <graphic xlink:href="1678-4170-abc-90-03-0163-00002-gf05.jpg"/></fig>
    </p>
    <p>As vari&#225;veis independentes preditoras da resposta cardioinibit&#243;ria foram a FC de base (p &lt; 0,05), o sexo masculino (OR: 2,61; IC95%: 1,3% a 5,1%) e a presen&#231;a de cardiopatia estrutural (OR: 3,28; IC 95%: 1,3% a 7,9%).</p>
    <p>A sensibilidade de uma assistolia <underline>&gt;</underline> 3 segundos para o diagn&#243;stico etiol&#243;gico dos epis&#243;dios de sincope ou queda inexplicada foi baixa (9,9%), mas sua especificidade foi boa (89,6%) (<xref ref-type="table" rid="t3">tab. 3</xref>). Essa especificidade foi melhor nas mulheres (95,3%), nos n&#227;o-usu&#225;rios de medica&#231;&#227;o cronotr&#243;pica negativa (93,7%) e nos pacientes sem cardiopatia estrutural (96,2%) <xref ref-type="table" rid="t3">(tab. 3</xref>).</p>
    <p content-type="asset">
      <table-wrap id="t3">
        <graphic xlink:href="1678-4170-abc-90-03-0163-00002-gt03.jpg"/></table-wrap>
    </p>
    <p><italic>Complica&#231;&#245;es da MSC -</italic> Nenhum indiv&#237;duo apresentou complica&#231;&#227;o cardiol&#243;gica relacionada &#224; MSC. Dois pacientes apresentaram complica&#231;&#245;es cerebrovasculares que n&#227;o deixaram seq&#252;elas. Em um homem de 56 anos, documentou-se presen&#231;a de d&#233;ficit no campo visual com regress&#227;o completa em sete dias, e em um homem de 71 anos verificou-se aparecimento de disartria e monoparesia do bra&#231;o esquerdo, ambas com regress&#227;o completa em 30 minutos.</p>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>A estimula&#231;&#227;o card&#237;aca artificial tem sido recomendada para os pacientes com s&#237;ncope inexplicada, nos quais a MSC provoca o aparecimento de resposta cardioinibit&#243;ria pura ou predominante<sup>1,2</sup>. A Sociedade Brasileira de Cardiologia (SBC) recomenda implante de marcapasso nos indiv&#237;duos com epis&#243;dios recorrentes de s&#237;ncope associados &#224; presen&#231;a de resposta cardioinibit&#243;ria &#224; MSC<sup>11</sup>. A SBC ressalta ser fundamental a confirma&#231;&#227;o da rela&#231;&#227;o entre a bradicardia e os sintomas, pois pausas ou bradicardia sem significado cl&#237;nico podem ser facilmente induzidas pela MSC de pacientes idosos, sobretudo quando em uso de drogas cronotr&#243;picas negativas<sup>11</sup>.</p>
    <p>A resposta cardioinibit&#243;ria estava presente em 52 dos 502 pacientes submetidos a MSC no HGB. Em 86,5% desses 52 pacientes, a resposta cardioinibit&#243;ria n&#227;o estava associada a passado de epis&#243;dios de s&#237;ncope ou queda, podendo ser considerada resposta falso positiva. Esse resultado suscita d&#250;vidas a respeito da indica&#231;&#227;o de marcapasso nos pacientes com s&#237;ncope e resposta cardioinibit&#243;ria &#224; MSC.</p>
    <p>Publica&#231;&#245;es recentes tamb&#233;m questionaram essa indica&#231;&#227;o de estimula&#231;&#227;o card&#237;aca artificial<sup>3-6</sup>. Uma dessas publica&#231;&#245;es sugere a reavalia&#231;&#227;o da defini&#231;&#227;o atual de resposta cardioinibit&#243;ria anormal<sup>6</sup>.</p>
    <p>O que seria uma resposta cardioinibit&#243;ria anormal? No passado, consideravam-se anormais todos os casos em que a MSC provocava o aparecimento de ritmo de escape juncional ou ventricular, de bloqueio atrioventricular ou de pausas superiores a 2 segundos<sup>12</sup>. Hoje, somente per&#237;odos de assistolia <underline>&gt;</underline> 3 segundos s&#227;o considerados patol&#243;gicos<sup>1,2,11</sup>. Esse valor baseia-se na experi&#234;ncia adquirida com a realiza&#231;&#227;o da manobra em milhares de indiv&#237;duos. H&#225; cerca de 50 anos, Franke<sup>13</sup> submeteu 3.900 pacientes a MSC. Esse autor observou pausas <underline>&gt;</underline> 3 segundos em menos de 10% deles e verificou que um per&#237;odo de assistolia dessa magnitude freq&#252;entemente provoca algum tipo de sintoma<sup>13</sup>. N&#250;meros semelhantes foram descritos por Sigler ap&#243;s a avalia&#231;&#227;o de 1.886 indiv&#237;duos das mais diversas faixas et&#225;rias<sup>14</sup>.</p>
    <p>Poucos trabalhos foram realizados com o objetivo prim&#225;rio de analisar a acur&#225;cia da pausa de 3 segundos no diagn&#243;stico da HSC. Em um dos mais citados pela literatura, McIntosh e cols. submeteram 25 idosos saud&#225;veis e assintom&#225;ticos a 5 segundos de MSC nas posi&#231;&#245;es supina e ortost&#225;tica<sup>15</sup>. A maior pausa encontrada (1.540 ms de assistolia) foi provocada pela MSCD na posi&#231;&#227;o supina<sup>15</sup>. Esse resultado refor&#231;ou a id&#233;ia de que o valor de 3 segundos &#233; adequado, sendo capaz de distinguir indiv&#237;duos com alentecimento normal da FC daqueles com resposta cardioinibit&#243;ria patol&#243;gica.</p>
    <p>Assim, em indiv&#237;duos assintom&#225;ticos e saud&#225;veis, o ponto de corte de 3 segundos parece distinguir, de forma adequada, indiv&#237;duos com pequena exacerba&#231;&#227;o de um reflexo considerado normal daqueles com resposta cardioinibit&#243;ria claramente patol&#243;gica.</p>
    <p>Contudo, um porcentual significativo de pacientes com s&#237;ncope apresenta alguma forma de cardiopatia estrutural<sup>16</sup>. H&#225; muito se sabe que nos pacientes com cardiopatia estrutural a preval&#234;ncia da resposta cardioinibit&#243;ria &#233; mais elevada que aquela encontrada em indiv&#237;duos saud&#225;veis<sup>9,17</sup>. Brignole e cols. descreveram a presen&#231;a de resposta cardioinibit&#243;ria em 2% de um grupo de 288 volunt&#225;rios saud&#225;veis, preval&#234;ncia que foi 8,5 vezes inferior &#224; encontrada por esses mesmos autores em 105 pacientes cardiopatas<sup>9</sup>.</p>
    <p>Dessa forma, nos portadores de cardiopatia estrutural, a interpreta&#231;&#227;o do significado cl&#237;nico da resposta cardioinibit&#243;ria &#233; mais dif&#237;cil. Nesses indiv&#237;duos, o ponto de corte de 3 segundos pode ser inadequado.</p>
    <p>Recentemente, Kerr e colaboradores avaliaram a preval&#234;ncia de HSC em uma popula&#231;&#227;o de idosos<sup>6</sup>. Recrutaram 272 volunt&#225;rios, com m&#233;dia de idade de 71 anos. Ap&#243;s a realiza&#231;&#227;o do exame cl&#237;nico e do eletrocardiograma, os 272 indiv&#237;duos foram subdivididos em dois grupos. Os 192 pacientes do primeiro grupo referiam hist&#243;ria de s&#237;ncope, queda ou tonteira durante o &#250;ltimo ano. Nenhum dos 80 pacientes do segundo grupo apresentava esses sintomas. Todos foram submetidos a 5 segundos de MSC nas posi&#231;&#245;es supina e ortost&#225;tica. Vinte e tr&#234;s por cento dos 192 indiv&#237;duos do grupo sintom&#225;tico apresentaram resposta cardioinibit&#243;ria &#224; MSC. Essa preval&#234;ncia foi inferior &#224;quela encontrada nos indiv&#237;duos sem hist&#243;ria de s&#237;ncope, queda ou tonteira. A resposta cardioinibit&#243;ria estava presente em 25% dos 80 pacientes sem esses sintomas<sup>6</sup>. Nesse estudo, a sensibilidade, a especificidade, o valor preditivo positivo e o valor preditivo negativo da resposta cardioinibit&#243;ria &#224; MSC para o diagn&#243;stico da causa dos epis&#243;dios de s&#237;ncope, queda ou tonteira foram, respectivamente, de 23%, 75%, 69% e 29%<sup>6</sup>.</p>
    <p>No estudo de Kerr e colaboradores, 5% dos 80 pacientes sem hist&#243;ria de s&#237;ncope, queda ou tonteira apresentaram assistolia superior a 7.277 ms<sup>6</sup>. Esse valor &#233; muito superior &#224;quele adotado pela Sociedade Europ&#233;ia de Cardiologia na defini&#231;&#227;o da resposta cardioinibit&#243;ria patol&#243;gica<sup>1</sup>, e pode ser atribu&#237;do ao fato de que 14% dos 80 pacientes avaliados eram coronariopatas, e ao fato de que um percentual significativo dessa popula&#231;&#227;o fazia uso de algum tipo de medica&#231;&#227;o cronotr&#243;pica negativa<sup>6</sup>.</p>
    <p>
      <bold>Conclus&#227;o</bold>
    </p>
    <p>Entre os 502 pacientes do HGB, 5% apresentaram pausas superiores a 4.482 ms no momento da MSCD e superiores a 2.418 ms durante a MSCE (<xref ref-type="table" rid="t2">tab. 2</xref>). Quando os homens s&#227;o exclu&#237;dos da an&#225;lise, encontram-se resultados muito pr&#243;ximos aos descritos por Franke e Sigler<sup>13,14</sup>. Entre as 243 mulheres estudadas, 5% apresentaram assistolia inferior a 2.672 ms durante a MSCD, e inferior a 1.836 ms durante a MSCE. Esse comportamento foi semelhante ao encontrado nos 155 pacientes sem cardiopatia estrutural e nos 199 indiv&#237;duos que n&#227;o faziam uso de medica&#231;&#227;o cronotr&#243;pica negativa (<xref ref-type="table" rid="t2">tab. 2</xref>).</p>
    <p>Assim, parece claro que nas mulheres, nos pacientes sem cardiopatia estrutural e nos n&#227;o-usu&#225;rios de medica&#231;&#227;o cronotr&#243;pica negativa o ponto de corte de 3 segundos &#233; adequado. Nesses indiv&#237;duos, a resposta cardioinibit&#243;ria &#224; MSC foi um achado espec&#237;fico para o diagn&#243;stico etiol&#243;gico dos epis&#243;dios de s&#237;ncope ou queda no &#250;ltimo ano (<xref ref-type="table" rid="t3">tab. 3</xref>).</p>
    <p>No entanto, em popula&#231;&#245;es com alta preval&#234;ncia de cardiopatia estrutural, em que o porcentual de usu&#225;rios de medica&#231;&#227;o cronotr&#243;pica negativa &#233; elevado, recomenda-se cautela na interpreta&#231;&#227;o do significado cl&#237;nico dos resultados da MSC. A resposta cardioinibit&#243;ria pode estar presente em pelo menos 10% desses indiv&#237;duos, sendo mais comum entre os homens, nos indiv&#237;duos bradic&#225;rdicos e nos portadores de cardiopatia estrutural.</p>
    <p>
      <fn id="back" fn-type="corresp">
        <p>Correspond&#234;ncia:</p>
        <p> Gustavo de Castro Lacerda </p>
        <p> Rua Hadock Lobo, 369/308 &#150; Est&#225;cio </p>
        <p> 20260-131 &#150; Rio de Janeiro, RJ &#150; Brasil </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="glacerda@cardiol.br">glacerda@cardiol.br</email>
        </p>
      </fn>
    </p>
    <p> Artigo recebido em 22/04/07; Revisado recebido em 20/06/07; Aceito em 08/08/07.</p>
  </body>
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  </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">Cardioinhibitory carotid sinus hypersensitivity: prevalence and predictors in 502 outpatients</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>BACKGROUND: Cardioinhibitory response (CIR) is defined as asystole &gt;3 seconds in response to 5-10 seconds of carotid sinus massage (CSM). Pacemaker implantation is indicated for patients with unexplained syncope episodes and CIR. OBJECTIVE: To determine the prevalence and predictors of CIR in patients with a high prevalence of cardiovascular disease, and assess the clinical significance of CIR in patients with a history of unexplained syncope or falls. METHODS: Cross-section design study. Outpatients, aged &gt;50 years, referred to the electrocardiography sector of a tertiary hospital. Those with dementia, carotid bruit, and history of myocardial infarction, stroke or transient ischemic attack in the preceding 3 months were excluded. CSM was performed by a single investigator, with the patients in the supine position. CSM was applied on the right side and then on the left side during 10 seconds each time. RESULTS: 502 patients underwent CSM. CIR was present in 52 patients (10.4%; 95% CI: 7.7%-13%). Independent predictors of CIR were male gender (OR: 2.61%; CI 95%: 1.3%-5.1%), structural heart disease (OR: 3.28%; CI 95%: 1.3%-7.9%) and baseline heart rate (P&lt;0.05). The sensitivity of the CIR to CSM in syncope evaluation was low (9.8%). Specificity was high (89.5%), being even better in women (95.3%) and in those without structural heart disease (96.2%). CONCLUSION: CIR was detected in 10.4% of the patients aged &gt; 50 years. In males and in patients with structural heart disease CIR was more common. In women and patients with no apparent structural heart disease, the presence of CIR was a highly specific finding in the evaluation of syncope or falls.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Carotid sinus</kwd>
        <kwd>syncope</kwd>
        <kwd>arrhythmia</kwd>
        <kwd>outpatients</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ORIGINAL ARTICLE</bold>
      </p>
      <p>
        <bold>Cardioinhibitory carotid sinus hypersensitivity: prevalence and predictors in 502 outpatients</bold>
      </p>
      <p>
        <bold>Gustavo de Castro Lacerda; Roberto Coury Pedrosa; Renato C&#244;rtes de Lacerda; Marcela Cedenilla dos Santos; Maur&#237;cio de Andrade Perez; Alfredo Brasil Teixeira; Aristarco Gon&#231;alves de Siqueira-Filho</bold>
      </p>
      <p>Universidade Federal do Rio de Janeiro &#150; Hospital Geral de Bonsucesso &#150; Rio de Janeiro, RJ - Brazil</p>
      <p>
        <xref ref-type="corresp" rid="back-body2">Mailing address</xref>
      </p>
      <p>
        <bold>SUMMARY</bold>
      </p>
      <p><bold>BACKGROUND: </bold>Cardioinhibitory response (CIR) is defined as asystole <underline>&gt;</underline>3 seconds in response to 5-10 seconds of carotid sinus massage (CSM). Pacemaker implantation is indicated for patients with unexplained syncope episodes and CIR.</p>
      <p><bold>OBJECTIVE: </bold>To determine the prevalence and predictors of CIR in patients with a high prevalence of cardiovascular disease, and assess the clinical significance of CIR in patients with a history of unexplained syncope or falls.</p>
      <p><bold>METHODS: </bold>Cross-section design study. Outpatients, aged <underline>&gt;</underline>50 years, referred to the electrocardiography sector of a tertiary hospital. Those with dementia, carotid bruit, and history of myocardial infarction, stroke or transient ischemic attack in the preceding 3 months were excluded. CSM was performed by a single investigator, with the patients in the supine position. CSM was applied on the right side and then on the left side during 10 seconds each time.</p>
      <p><bold>RESULTS: </bold>502 patients underwent CSM. CIR was present in 52 patients (10.4%; 95% CI: 7.7%-13%). Independent predictors of CIR were male gender (OR: 2.61%; CI 95%: 1.3%-5.1%), structural heart disease (OR: 3.28%; CI 95%: 1.3%-7.9%) and baseline heart rate (P&lt;0.05). The sensitivity of the CIR to CSM in syncope evaluation was low (9.8%). Specificity was high (89.5%), being even better in women (95.3%) and in those without structural heart disease (96.2%).</p>
      <p><bold>CONCLUSION: </bold>CIR was detected in 10.4% of the patients aged <underline>&gt;</underline> 50 years. In males and in patients with structural heart disease CIR was more common. In women and patients with no apparent structural heart disease, the presence of CIR was a highly specific finding in the evaluation of syncope or falls. (Arq Bras Cardiol 2008; 90(3):148-155)</p>
      <p><bold>Key words:</bold> Carotid sinus; syncope; arrhythmia; outpatients.</p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p>Carotid sinus hypersensitivity (CSH) is the exacerbation of a reflex present in healthy individuals. The European Society of Cardiology defined this condition as asystole lasting for at least 3 seconds, or a drop in systolic blood pressure (BP) of at least 50 mmHg, provoked by 5 to 10 seconds of carotid sinus massage (CSM).<sup>1</sup></p>
      <p>In most individuals, CSM causes a slight reduction in heart rate (HR), as well as in tensional levels. Two forms of response to CSM can be considered pathological: the cardioinhibitory response characterized by the presence of asystole lasting for at least 3 seconds, and the vasopressor form characterized by a reduction in systolic blood pressure (<underline>&gt;</underline> 50 mmHg). Both may occur independently (pure cardioinhibitory or vasodepressor responses), or as a combination of the two (mixed response).<sup>1,2</sup></p>
      <p>Doubts still exist about the clinical meaning of the cardioinhibitory response.<sup>3,4</sup> CSM may produce asystole lasting <underline>&gt;</underline>3 seconds in a significant portion of the population.<sup>5,6</sup> This behavior occurs more frequently among subjects with a history of syncope, particularly the elderly and those with structural heart disease.<sup>7,8,9</sup></p>
      <p>In Brazil, no studies have been published that evaluate the prevalence of cardioinhibitory response to CSM. In foreign literature, predictors of cardioinhibitory response have been described in only a few studies, most of which with a small number of patients.<sup>6,10</sup></p>
      <p>The aim of this study was to determine the prevalence and predictors of cardioinhibitory response to CSM in outpatients aged <underline>&gt;</underline>50 years and with a high prevalence of cardiovascular disease. Moreover, we intended to evaluate the clinical meaning of the cardioinhibitory response to CSM among patients with a history of syncope or falls during the preceding year.</p>
      <p>
        <bold>Methods</bold>
      </p>
      <p><italic>Study design -</italic> This is a cross-section design study conducted at the cardiology outpatient unit of the <italic>Hospital Geral de Bonsucesso</italic> (HGB), a public tertiary hospital. Patient recruitment was started after approval of the research protocol by the hospital's Research Ethics Committee. All patients were asked to sign the informed consent form.</p>
      <p><italic>Patients -</italic> Outpatients aged <underline>&gt;</underline>50 years, who had been referred after routine cardiological examination and patients who were referred by physicians from other specialties (clinical or surgical) to undergo electrocardiogram testing (ECG), were randomly selected.</p>
      <p>Individuals selected were interviewed by the main investigator of this study and were submitted to clinical evaluation. Patients were informed about the objectives of the study and the risks of CSM. During the interview, the primary focus was on the patient's history of unexplained syncopal episodes or falls.</p>
      <p>Syncope was defined as a sudden and transient loss of consciousness, associated with loss of postural tone.</p>
      <p>Unexplained falling was considered any situation in which the individual fell down without any accidental (stumbling over or being pushed) or medical (convulsion, stroke, alcohol abuse, orthostatic hypotension, and arrhythmia) reason. Patients with more than 3 falls in the preceding year were also considered as unexplained fallers, even if they reported a history of an accidental cause for these episodes.</p>
      <p>Patients who did not sign the informed consent form and those in whom CSM was not feasible (individuals morbidly obese, with neck wounds and tracheostomy) were excluded from the study. Patients with dementia, carotid murmur or carotid Doppler exam showing <underline>&gt;</underline>50% carotid stenosis, individuals with a history of AMI,stroke, or TIA in the preceding 3 months, those with symptomatic bradyarrhythmias, those with pacemakers and those with a history of ventricular arrhythmia were also excluded.</p>
      <p><italic>CSM technique employed -</italic> CSM was performed in a facility equipped with a cardiac defibrillator, transcutaneous pacemaker and all items required to perform cardiopulmonary resuscitation. The first author of this study was responsible for performing CSM in all cases.</p>
      <p>CSM was carried out only in the supine position, initiating on the right side. Longitudinal massage was applied for 10 seconds over the point of maximal carotid pulse, just above the thyroid cartilage and below the angle of the jaw. In patients who did not present any immediate complication after one minute, the procedure was repeated on the left side. Heart rate and cardiac rhythm changes produced by CSM were recorded by the Cardiofax 9010B<sup>&#174;</sup> electrocardiograph at a speed of 25 mm/s.</p>
      <p>After CSM, all patients were asked about the presence of symptoms during the procedure.</p>
      <p>The greatest R-R interval produced by CSM was measured with the help of a ruler, a magnifying glass and a compass with a precision of 20 ms.</p>
      <p><italic>Outcome -</italic> Cardioinhibitory response to CSM. Patients considered as having cardioinhibitory responses were those in whom CSM produced asystole <underline>&gt;</underline>3 seconds, irrespective of the blood pressure behavior and the presence of symptoms.</p>
      <p><italic>Statistical analysis -</italic> In order to study the prevalence of cardioinhibitory response with 95% safety, 427 individuals would have to undergo CSM. This number was obtained based on the estimate that the prevalence of cardioinhibitory response in patients <underline>&gt;</underline>50 years of age seen at HGB outpatient cardiology unit is equal to 12% &#177; 3%, and that the number of patients seen per year at this outpatient clinic is equal to 8 thousand. As our objective was also to study the predictors of cardioinhibitory response, we decided to increase the size of the sample to 500 patients.</p>
      <p>Comparisons between the greatest R-R interval registered during CSM performed on the right side (RCSM) and on the left side (LCSM) in the overall population, male patients, female patients, users and non-users of negative chronotropic drugs, patients with and without structural heart disease, were performed using the Mann-Whitney test.</p>
      <p>The dichotomic predictor variables of the presence of a cardioinhibitory response were determined through contingency tables and determination of the relative risk. Fisher's exact test was used to establish the value of <italic>p</italic>. Each association with <italic>p</italic>&lt;0.05 was considered significant. The continuous variables predictors of the presence of cardioinhibitory response were compared with the use of the T test. The variables with <italic>p</italic>&lt;0.1 in the univariate analysis were included in a binary logistic regression model (<italic>stepwise forward Wald</italic>).</p>
      <p>
        <bold>Results</bold>
      </p>
      <p>
        <bold>Description of the population:</bold>
      </p>
      <p>During the recruitment period, 1,686 patients aged <underline>&gt;</underline>50 years were seen at the HGB electrocardiography outpatient unit, and 562 patients (33.3%) were randomly selected. Sixty patients were excluded from the study (<xref ref-type="fig" rid="en_02f1-body2">Figure 1</xref>). <xref ref-type="table" rid="en_02t1-body2">Table 1</xref> exhibits a summary of the characteristics of the 502 individuals who underwent CSM.</p>
      <p content-type="asset">
        <fig id="en_02f1-body2">
          <graphic xlink:href="1678-4170-abc-90-03-0163-00002-gf01-en.jpg"/></fig>
      </p>
      <p content-type="asset">
        <table-wrap id="en_02t1-body2">
          <graphic xlink:href="1678-4170-abc-90-03-0163-00002-gt01-en.jpg"/></table-wrap>
      </p>
      <p>The mean value of the greatest R-R interval produced by RCSM was greater than the mean value of the greatest R-R interval produced by LCSM. This behavior was observed in the overall population, in men, in women and in 4 groups of patients (<xref ref-type="table" rid="en_02t2-body2">Table 2</xref>). The mean value of the greatest R-R interval produced by CSM in men was greater than that recorded among women (<italic>p</italic>&lt;0.05). The mean value of the greatest R-R interval produced by CSM in users of negative chronotropic drugs was greater than that in non-users of negative chronotropic drugs (<italic>p</italic>&lt;0.05), and the mean value of the greatest R-R interval produced by CSM in patients with structural heart disease was greater than that observed among individuals who did not have structural heart disease (<italic>p</italic>&lt;0.05) (<xref ref-type="table" rid="en_02t2-body2">Table 2</xref>).</p>
      <p content-type="asset">
        <table-wrap id="en_02t2-body2">
          <graphic xlink:href="1678-4170-abc-90-03-0163-00002-gt02-en.jpg"/></table-wrap>
      </p>
      <p>
        <bold>Prevalence and predictors of cardioinhibitory response to CSM</bold>
      </p>
      <p>CSM produced cardioinhibitory responses in 52 patients (prevalence: 10.4%; CI 95%: 7.7% to 13%). In 34 individuals, the cardioinhibitory response was detected exclusively during RCSM, and in 9, exclusively during LCSM. Nine patients presented a cardioinhibitory response during RCSM and LCSM(<xref ref-type="fig" rid="en_02f2-body2">Figures 2</xref> and <xref ref-type="fig" rid="en_02f3-body2">3</xref>).</p>
      <p content-type="asset">
        <fig id="en_02f2-body2">
          <graphic xlink:href="1678-4170-abc-90-03-0163-00002-gf02-en.jpg"/></fig>
      </p>
      <p content-type="asset">
        <fig id="en_02f3-body2">
          <graphic xlink:href="1678-4170-abc-90-03-0163-00002-gf03-en.jpg"/></fig>
      </p>
      <p><xref ref-type="table" rid="en_02t1-body2">Table 1</xref> displays the characteristics of patients with and without cardioinhibitory response.</p>
      <p>Patients with cardioinhibitory response had a baseline HR lower than those who did not present this response (<xref ref-type="table" rid="en_02t1-body2">Table 1</xref>, <xref ref-type="fig" rid="fig4-body2">Figure 4</xref>).</p>
      <fig id="fig4-body2">
        <graphic xlink:href="1678-4170-abc-90-03-0163-00002-gf04-en.jpg"/></fig>
      <p>No significant relationship was observed between the history of syncope or falls and the presence of a cardioinhibitory response to CSM. In the univariate analysis, male gender (R-R: 2.82; <italic>p</italic>&lt;0.05), presence of known heart disease (R-R: 2.49) and structural heart disease (OR: 3.42; <italic>p</italic>&lt;0.05) were the greatest predictors of the presence of a cardioinhibitory response to CSM (<xref ref-type="fig" rid="fig5-body2">Figure 5</xref>).</p>
      <fig id="fig5-body2">
        <graphic xlink:href="1678-4170-abc-90-03-0163-00002-gf05-en.jpg"/></fig>
      <p>Independent predictor variables of cardioinhibitory response were baseline HR (<italic>p</italic>&lt;0.05), male gender (OR: 2.61; CI 95%: 1.3%) and the presence of structural heart disease (OR: 3.28; CI 95%: 1.3% to 7.9%).</p>
      <p>The sensitivity of an asystole <underline>&gt;</underline>3 seconds for the etiologic diagnosis of unexplained syncope or falls was low (9.9%), but its specificity was high (89.6%) (<xref ref-type="table" rid="en_02t3-body2">Table 3</xref>). This specificity was higher among women (95.3%), in those who did not use negative chronotropic agents (93.7%) and in patients with no structural heart disease (96.2%) (<xref ref-type="table" rid="en_02t3-body2">Table 3</xref>).</p>
      <p content-type="asset">
        <table-wrap id="en_02t3-body2">
          <graphic xlink:href="1678-4170-abc-90-03-0163-00002-gt03-en.jpg"/></table-wrap>
      </p>
      <p>
        <bold>Complications from CSM:</bold>
      </p>
      <p>No individual developed cardiac complications associated with CSM. Two patients had cerebrovascular complications with no sequelae. A 56-year-old man developed a visual field deficit which receded completely within 7 days, and a 71-year-old man experienced dysarthria and left-arm monoparesis, both of which receded within 30 minutes.</p>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>Pacemaker implantation is recommended for patients with unexplained syncope in which CSM produces a pure or predominant cardioinhibitory response.<sup>1,2</sup> The Brazilian Society of Cardiology (SBC) recommends implantation of pacemakers for individuals with recurrent episodes of syncope associated with the presence of a cardioinhibitory response to CSM.<sup>11</sup> SBC stresses the importance of confirmation of the relationship between bradycardia and symptoms, since pauses or bradycardia with no clinical significance may easily be induced by CSM in elderly patients, especially when they are using negative chronotropic drugs.<sup>11</sup></p>
      <p>CSM produced cardioinhibitory responses in 52 of the 502 patients who underwent the procedure at HGB. In 86.5% of these 52 patients, the cardioinhibitory response was not associated with a past history of syncopal episodes or falls, and could be considered a false-positive response. This result raises questions about the indication of pacemaker implantation for patients who experience syncope and cardioinhibitory responses to CSM.</p>
      <p>Recent publications have also questioned the indication of artificial cardiac stimulation.<sup>3-6</sup> One of these publications suggests a reevaluation of the current definition of abnormal cardioinhibitory response.<sup>6</sup></p>
      <p>In the past, all cases in which CSM produced the appearance of a junctional or ventricular escape rhythm, atrioventricular block or pauses greater than 2 seconds were considered abnormal.<sup>12</sup> Today, only asystole periods lasting <underline>&gt;</underline>3 seconds are considered pathological.<sup>1,2,11</sup> This value is based on the experience acquired with the performance of the maneuver in thousands of individuals. Approximately 50 years ago, Franke performed CSM in 3,900 patients. This author recorded pauses <underline>&gt;</underline>3 seconds in less than 10% of the patients, and observed that such a period of asystole frequently produced some type of symptom. <sup>13</sup> Similar numbers were described by Sigler after the evaluation of 1,886 individuals from different age groups.<sup>14</sup></p>
      <p>Few trials have been conducted with the primary aim of analyzing the accuracy of the 3-second pause for the diagnosis of CSH. In one of the most cited studies in literature, McIntosh <italic>et al.</italic> performed CSM in 25 asymptomatic healthy elderly patients during 5 seconds in the supine and upright positions.<sup>15</sup> The greatest pause observed (1,540 ms asystole) was produced by RCSM performed in the supine position.<sup>15</sup> This result reinforced the idea that the value of 3 seconds is appropriate and capable of distinguishing individuals with normal deceleration of the heart rate from those with a pathological cardioinhibitory response.</p>
      <p>Therefore, in asymptomatic and healthy individuals, the 3-second cutoff point seems to adequately distinguish individuals with a slight exacerbation of a reflex considered normal from those with a clearly pathological cardioinhibitory response.</p>
      <p>However, a significant percentage of patients with syncopal episodes have some form of structural heart disease.<sup>16</sup> It has long been known that in patients with structural heart disease the prevalence of the cardioinhibitory response is higher than that observed in healthy individuals<sup>9,17</sup>. Brignole <italic>et al</italic>. describe the presence of a cardioinhibitory response in 2% of a group of 288 healthy volunteers. This prevalence was 8.5 times lower than what they observed in 105 patients with heart diseases.<sup>9</sup></p>
      <p>Therefore, interpretation of the clinical meaning of a cardioinhibitory response in patients with structural heart disease is more difficult. In these individuals, the 3-second cut-off point may be inadequate.</p>
      <p>Recently, Kerr <italic>et al.</italic> evaluated the prevalence of CSH in a population of elderly people.<sup>6</sup> They recruited 272 volunteers with a mean age of 71 years. After clinical examination and ECG, the 272 individuals were subdivided into 2 groups. The 192 patients in the first group reported a history of syncope, falling or dizziness during the preceding year. None of the 80 patients in the second group had experienced these symptoms. All of them underwent 5 seconds of CSM in the supine and upright positions. Twenty-three percent of the 192 individuals in the symptomatic group developed cardioinhibitory responses to CSM. This prevalence was lower than that recorded for individuals with no history of syncope, falling or dizziness. Cardioinhibitory responses were observed in 25% of the 80 patients who did not have these symptoms.<sup>6</sup> In this study, sensitivity, specificity, positive predictive value and negative predictive value of the cardioinhibitory response to CSM for the diagnosis of the causes of episodes of syncope, falling or dizziness were 23%, 75%, 69% and 29%, respectively.<sup>6</sup></p>
      <p>In the study by Kerr <italic>et al.</italic>, 5% of the 80 patients with no history of syncope, falling or dizziness developed asystole greater than 7277 ms.<sup>6</sup> This value is much greater than that adopted by the European Society of Cardiology for the definition of a cardioinhibitory response<sup>1</sup>, and can be attributed to the fact that 14% of the 80 patients evaluated had heart diseases, and a significant percentage of this population used some type of negative chronotropic medication.<sup>6</sup></p>
      <p>Five percent of the 502 patients studied at HGB presented pauses greater than 4482 ms during RCSM and greater than 2418 ms during LCSM (<xref ref-type="table" rid="en_02t2-body2">Table 2</xref>). When men are excluded from the analysis, the results are very close to those described by Franke and Sigler.<sup>13,14</sup> Ninety-five percent of the 243 women presented asystole of less than 2672 ms during RCSM and less than 1836 ms during LCSM. This behavior was similar to that observed in the 155 patients with no structural heart disease and in the 199 individuals who were not taking any negative chronotropic medication (<xref ref-type="table" rid="en_02t2-body2">Table 2</xref>).</p>
      <p>Thus, it seems clear that in women, in patients with no structural heart disease, and in those who were not taking negative chronotropic medication, the 3-second cut-off point is appropriate. In these individuals, the cardioinhibitory response to CSM was a specific finding for the etiologic diagnosis of syncope or falls in the preceding year (<xref ref-type="table" rid="en_02t3-body2">Table 3</xref>).</p>
      <p>Nevertheless, in populations with a high prevalence of structural heart disease in which the percentage of users of negative chronotropic medication is high, caution is recommended in the interpretation of the clinical significance of CSM results. Cardioinhibitory response may be present in at least 10% of these individuals, and is more common in men, in bradycardic subjects and in those with structural heart disease.</p>
      <p>
        <bold>References</bold>
      </p>
      <p>
        <fn id="back-body2" fn-type="corresp">
          <p>Mailing address:</p>
          <p> Gustavo de Castro Lacerda</p>
          <p> Rua Hadock Lobo, 369/308 - Est&#225;cio</p>
          <p> 20260-131 - Rio de Janeiro, RJ - Brazil</p>
          <p> E-mail: </p>
          <p>
            <email xlink:href="glacerda@cardiol.br">glacerda@cardiol.br</email>
          </p>
        </fn>
      </p>
      <p>Manuscript received April 22, 2007; revised manuscript received June 20, 2007; accepted August 8, 2007.</p>
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