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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">MBDNKbVgPMRkprpt8jZ5nRz</article-id>
      <article-id pub-id-type="other">00009</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2008000400009</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(08)09000409</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2008000400009</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Relev&#226;ncia diagn&#243;stica da massagem do seio carot&#237;deo durante teste de inclina&#231;&#227;o</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Benchimol</surname>
            <given-names>Marcos</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Oliveira-Souza</surname>
            <given-names>Ricardo</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <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">Cl&#237;nica Benchimol</institution>
        <country country="BR">Brasil</country>
      </aff>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="state">Rio de Janeiro</named-content>
        </addr-line>
        <institution content-type="orgname">Universidade Federal do Estado do Rio de Janeiro</institution>
        <country country="BR">Brazil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>04</month>
        <year>2008</year>
      </pub-date>
      <volume>90</volume>
      <issue>4</issue>
      <fpage>288</fpage>
      <lpage>292</lpage>
      <history>
        <date date-type="received">
          <day>09</day>
          <month>06</month>
          <year>2007</year>
        </date>
        <date date-type="accepted">
          <day>30</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: As s&#237;ncopes por hipersensibilidade do seio carot&#237;deo (HSC) podem ser pouco diagnosticadas por causa da baixa desconfian&#231;a diagn&#243;stica ou do medo de complica&#231;&#245;es da pr&#243;pria massagem do seio carot&#237;deo. OBJETIVO: Investigar o papel da hipersensibilidade do seio carot&#237;deo (HSC) em desmaios n&#227;o-convulsivos e quedas inexplicadas. M&#201;TODOS: Duzentos e cinq&#252;enta e nove pacientes com idade m&#233;dia de 50&#177;24 anos, encaminhados para investiga&#231;&#227;o de desmaios n&#227;o-convulsivos e quedas inexplicadas, foram submetidos ao Teste da Mesa Inclinada (TI) sem ("passivo") e com provoca&#231;&#227;o farmacol&#243;gica ("sensibilizado"). Exames cl&#237;nicos e complementares n&#227;o revelaram causa &#243;bvia para as queixas. Cinq&#252;enta e cinco volunt&#225;rios com idade m&#233;dia de 57&#177;21 anos sem hist&#243;ria de epilepsia, desmaios e quedas serviram de controles. Todos os participantes foram submetidos ao TI precedido por estimula&#231;&#227;o digital dos seios carot&#237;deos a zero e a 60&#186;. RESULTADOS: A estimula&#231;&#227;o dos seios carot&#237;deos foi positiva em 4 controles. O diagn&#243;stico cl&#237;nico de HSC foi endossado por resposta positiva &#224; estimula&#231;&#227;o carot&#237;dea a 60&#186; em 28 pacientes, em sua maioria homens idosos. A estimula&#231;&#227;o carot&#237;dea foi positiva a 0&#186; em apenas tr&#234;s desses pacientes. N&#227;o houve diferen&#231;a estat&#237;stica no TI entre os pacientes com e sem HSC. CONCLUS&#195;O: A estimula&#231;&#227;o dos seios carot&#237;deos a 60&#186; deve ser inclu&#237;da na avalia&#231;&#227;o rotineira de pacientes com desmaios n&#227;o-convulsivos ou quedas inexplicadas, uma vez que os exames cardiovasculares de rotina, incluindo o TI, n&#227;o foram &#250;teis para estabelecer o diagn&#243;stico nesses casos. Novos estudos em indiv&#237;duos normais s&#227;o necess&#225;rios para estabelecer o significado da resposta positiva &#224; estimula&#231;&#227;o carot&#237;dea na aus&#234;ncia de hist&#243;ria de desmaios ou quedas.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>S&#237;ncope</kwd>
        <kwd>hipersensibilidade</kwd>
        <kwd>seio carot&#237;deo</kwd>
        <kwd>teste da mesa inclinada</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>29</day>
        <month>05</month>
        <year>2008</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>ARTIGO ORIGINAL</bold>
    </p>
    <p> Relev&#226;ncia diagn&#243;stica da massagem do seio carot&#237;deo durante teste de inclina&#231;&#227;o</p>
    <p>
      <bold>Marcos Benchimol<sup>I, II</sup>; Ricardo Oliveira-Souza<sup>I</sup></bold>
    </p>
    <p><sup>I</sup>Universidade Federal do Estado do Rio de Janeiro (UNI-RIO) </p>
    <p><sup>II</sup>Cl&#237;nica Benchimol, Rio de Janeiro, RJ - Brasil </p>
    <p>
      <xref ref-type="corresp" rid="end">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold> FUNDAMENTO:</bold> As s&#237;ncopes por hipersensibilidade do seio carot&#237;deo (HSC) podem ser pouco diagnosticadas por causa da baixa desconfian&#231;a diagn&#243;stica ou do medo de complica&#231;&#245;es da pr&#243;pria massagem do seio carot&#237;deo. </p>
    <p><bold>OBJETIVO:</bold> Investigar o papel da hipersensibilidade do seio carot&#237;deo (HSC) em desmaios n&#227;o-convulsivos e quedas inexplicadas. </p>
    <p><bold>M&#201;TODOS:</bold> Duzentos e cinq&#252;enta e nove pacientes com idade m&#233;dia de 50&#177;24 anos, encaminhados para investiga&#231;&#227;o de desmaios n&#227;o-convulsivos e quedas inexplicadas, foram submetidos ao Teste da Mesa Inclinada (TI) sem ("passivo") e com provoca&#231;&#227;o farmacol&#243;gica ("sensibilizado"). Exames cl&#237;nicos e complementares n&#227;o revelaram causa &#243;bvia para as queixas. Cinq&#252;enta e cinco volunt&#225;rios com idade m&#233;dia de 57&#177;21 anos sem hist&#243;ria de epilepsia, desmaios e quedas serviram de controles. Todos os participantes foram submetidos ao TI precedido por estimula&#231;&#227;o digital dos seios carot&#237;deos a zero e a 60&#186;. </p>
    <p><bold>RESULTADOS:</bold> A estimula&#231;&#227;o dos seios carot&#237;deos foi positiva em 4 controles. O diagn&#243;stico cl&#237;nico de HSC foi endossado por resposta positiva &#224; estimula&#231;&#227;o carot&#237;dea a 60&#186; em 28 pacientes, em sua maioria homens idosos. A estimula&#231;&#227;o carot&#237;dea foi positiva a 0&#186; em apenas tr&#234;s desses pacientes. N&#227;o houve diferen&#231;a estat&#237;stica no TI entre os pacientes com e sem HSC. </p>
    <p><bold>CONCLUS&#195;O:</bold> A estimula&#231;&#227;o dos seios carot&#237;deos a 60&#186; deve ser inclu&#237;da na avalia&#231;&#227;o rotineira de pacientes com desmaios n&#227;o-convulsivos ou quedas inexplicadas, uma vez que os exames cardiovasculares de rotina, incluindo o TI, n&#227;o foram &#250;teis para estabelecer o diagn&#243;stico nesses casos. Novos estudos em indiv&#237;duos normais s&#227;o necess&#225;rios para estabelecer o significado da resposta positiva &#224; estimula&#231;&#227;o carot&#237;dea na aus&#234;ncia de hist&#243;ria de desmaios ou quedas. </p>
    <p><bold>Palavras-chave:</bold> S&#237;ncope, hipersensibilidade, seio carot&#237;deo, teste da mesa inclinada.</p>
    <p>
      <bold>Introdu&#231;&#227;o </bold>
    </p>
    <p>A descri&#231;&#227;o original da s&#237;ncope convulsiva por massagem do seio carot&#237;deo foi tamb&#233;m a primeira a interpretar corretamente a bradicardia e a hipotens&#227;o como respostas reflexas anormais e sua normaliza&#231;&#227;o por aplica&#231;&#227;o pr&#233;via de atropina<sup>1</sup>. Atualmente, a <italic>hipersensibilidade</italic> do seio carot&#237;deo (HSC) &#233; diagnosticada em pacientes nos quais a <italic>massagem</italic> do seio carot&#237;deo (MSC) induz assistolia por mais de 3 segundos (tipo cardioinibit&#243;rio) ou queda da press&#227;o sist&#243;lica superior a 50 mmHg (tipo vasodepressor)<sup>2</sup>. Estudos subseq&#252;entes estabeleceram a import&#226;ncia da HSC como causa de desmaios<sup>3 </sup>e ataques de quedas (<italic>drop attacks</italic>)<sup>4</sup>, assim como o aumento da reatividade reflexa do seio carot&#237;deo com o envelhecimento, principalmente nos homens<sup>5</sup>. A inclus&#227;o da MSC no Teste de Mesa Inclinado (TI)<sup>6</sup> ampliou o leque das causas das s&#237;ncopes neurocardiog&#234;nicas, particularmente as ocasionadas por HSC<sup>7</sup>. Todavia, a despeito do n&#250;mero crescente de estudos que utilizam a MSC em condi&#231;&#245;es controladas, o significado cl&#237;nico da HSC permanece obscuro, principalmente em vista de sua preval&#234;ncia inesperadamente elevada em pessoas que nunca desmaiaram na vida<sup>8</sup>. A presente investiga&#231;&#227;o teve por principais objetivos: 1) reportar uma s&#233;rie de indiv&#237;duos encaminhados ao TI para investiga&#231;&#227;o de desmaios ou quedas injustificadas; 2) determinar a preval&#234;ncia da HSC induzida por MSC nesta s&#233;rie de pacientes, e 3) a utilidade do protocolo do TI utilizado em nosso servi&#231;o a partir de um grupo de volunt&#225;rios sem hist&#243;ria de quedas ou desmaios.</p>
    <p>
      <bold>M&#233;todos </bold>
    </p>
    <p>Cento e setenta mulheres e 89 homens com idades de 10 a 96 anos (m&#233;dia = 50 &#177; 24 anos) foram encaminhados para investiga&#231;&#227;o de "desmaios" ou quedas inexplicadas ("ataques de quedas") que haviam ocorrido a primeira vez v&#225;rios meses antes (m&#233;dia = 53 &#177; 100 meses). Dezenove pacientes com MSC+ utilizavam regularmente benzodiazep&#237;nicos (n = 2), anticonvulsivantes (n = 3), hipotensores (n = 15), diur&#233;ticos (n = 5) e anticoagulante oral (n = 1). O exame f&#237;sico, ECG e ecocardiograma foram normais ou sem rela&#231;&#227;o com os sintomas de interesse. Cinq&#252;enta e cinco volunt&#225;rios (32 mulheres e 23 homens) sem hist&#243;ria de quedas ou desmaios, com 16 a 88 anos de idade (m&#233;dia = 57 &#177; 21 anos), serviram de controle para o TI. Homens e mulheres n&#227;o diferiram em idade no grupo de pacientes (<italic>U</italic> = 5.200, <italic>p</italic> &gt; 0,56) ou controles (<italic>U</italic> = 329, <italic>p</italic> &gt; 0,98). Tampouco se constatou diferen&#231;a entre os grupos quanto &#224; composi&#231;&#227;o de sexo (c<sup>2</sup> = 0,77, <italic>p</italic> &gt; 0,38). Todos forneceram consentimento informado por escrito antes do ingresso no estudo, que foi aprovado pelo Comit&#234; de &#201;tica do Hospital Universit&#225;rio Gaffr&#233;e e Guinle.</p>
    <p>
      <bold>Teste inclinado e MSC</bold>
    </p>
    <p>O TI foi realizado entre 14 e 17 horas<sup>9</sup>, em sala silenciosa, ilumina&#231;&#227;o t&#234;nue e temperatura ambiente agrad&#225;vel, de acordo com recomenda&#231;&#245;es t&#233;cnicas amplamente aceitas<sup>10</sup>. A mesa de exame (Carci, S&#227;o Paulo, Brasil), equipada com sistema TEB para monitora&#231;&#227;o cont&#237;nua do ECG e apoio para os p&#233;s, permite inclina&#231;&#245;es de 60 a 80&#186;. A press&#227;o arterial foi aferida por aparelho oscilom&#233;trico e os valores confirmados com esfigmoman&#244;metro a intervalos regulares. Bandeja de reanima&#231;&#227;o foi mantida ao alcance por todo o tempo de exame. Solicitou-se a cada indiv&#237;duo que cumprisse jejum de 12 horas e, quando poss&#237;vel, que suspendesse os medicamentos 24 horas antes. Ap&#243;s 10 minutos de repouso em dec&#250;bito dorsal, o examinador massageava manualmente por 5 segundos a regi&#227;o do pesco&#231;o onde a pulsa&#231;&#227;o da car&#243;tida atingia intensidade m&#225;xima, geralmente no plano da borda superior da cartilagem cric&#243;ide, come&#231;ando pelo lado direito. Em seguida, inclinava a mesa a 60&#186; e repetia a manobra de cada lado. Observa&#231;&#245;es anteriores mostraram que a massagem dos seios carot&#237;deos pode ser inteiramente normal a zero grau e tornar-se positiva apenas ap&#243;s inclina&#231;&#227;o<sup>11</sup>. O TI consistiu de duas condi&#231;&#245;es<sup>10</sup>: 1) uma condi&#231;&#227;o "passiva" (isto &#233;, sem interven&#231;&#227;o farmacol&#243;gica) e 2) uma condi&#231;&#227;o farmacologicamente "sensibilizada", em que se ministrava 1,25 mg de dinitratro de isosorbida por via sublingual, para provocar sintomas inaparentes na condi&#231;&#227;o passiva. Cada condi&#231;&#227;o durava 25 minutos ou menos, em caso de pr&#233;-s&#237;ncope. Quando positivo na primeira fase, conclu&#237;a-se o teste sem passar &#224; condi&#231;&#227;o sensibilizada. O TI foi conduzido normalmente nos casos de MSC positiva. O TI foi considerado anormal ("positivo") se sintomas sincopais ou pr&#233;-sincopais mediados por mecanismos neurais ocorressem por causa de hipotens&#227;o, bradicardia, ou ambos, quer o indiv&#237;duo atestasse ou n&#227;o a replica&#231;&#227;o dos sintomas que o acometiam na vida real. A MSC foi considerada positiva se houvesse queda m&#237;nima de 50 mmHg da press&#227;o arterial sist&#243;lica ou bradicardia/asistolia<sup>2,10</sup>. Sopro carot&#237;deo, acidentes cerebrovasculares ou infarto agudo do mioc&#225;rdio nos seis meses precedentes ou hist&#243;ria de arritmia ventricular grave constitu&#237;ram contra-indica&#231;&#227;o para a realiza&#231;&#227;o do exame.</p>
    <p>
      <bold>An&#225;lise estat&#237;stica dos resultados</bold>
    </p>
    <p>Os resultados s&#227;o descritos por m&#233;dias e desvios padr&#227;o. Poss&#237;veis associa&#231;&#245;es entre vari&#225;veis categ&#243;ricas foram inferidas pelo teste do c<sup>2</sup>. A signific&#226;ncia de diferen&#231;as entre grupos foi aferida pelos testes de Mann-Whitney (<italic>U</italic>) e Exato de Fisher<sup>12</sup>. A contribui&#231;&#227;o relativa de idade, sexo, resultado do TI, e &#237;ndices fisiol&#243;gicos (press&#227;o arterial e freq&#252;&#234;ncia card&#237;aca) para ocorr&#234;ncia da HSC foi inferida por regress&#227;o log&#237;stica binomial. A regress&#227;o log&#237;stica binomial &#233; apropriada para vari&#225;veis dependentes dicot&#244;micas (por exemplo, MSC+ vs. MSC-), &#224;s quais se atribui valor 1 &#224; de principal interesse (por exemplo, MSC+) e zero &#224; outra (por exemplo, MSC-). O tamanho do efeito e o sentido da associa&#231;&#227;o entre as vari&#225;veis independentes s&#227;o expressos como <italic>odds ratios</italic> (<bold>OR</bold>). Cada <bold>OR</bold> pode variar de zero a 0,999 (no caso de uma rela&#231;&#227;o inversa) ou de 1,001 ao infinito (no caso de uma rela&#231;&#227;o direta); quando <bold>OR</bold> = 1, as vari&#225;veis s&#227;o estatisticamente independentes<sup>13</sup>. O tamanho do efeito global da regress&#227;o log&#237;stica foi aferido pelo coeficiente R<sup>2</sup> de Nagelkerke, que, &#224; semelhan&#231;a do coeficiente de determina&#231;&#227;o m&#250;ltipla (R<sup>2</sup>), varia entre zero e 1. Adotamos limiar de signific&#226;ncia de 0,05, bicaudado, para todos os testes estat&#237;sticos. Os c&#225;lculos foram realizados no <bold>SPSS</bold> for Windows, v. 13.0 (<bold>SPSS</bold> Inc, 2004).</p>
    <p>
      <bold>Resultados </bold>
    </p>
    <p>Os principais resultados est&#227;o apresentados na <xref ref-type="table" rid="tab1">Tabela 1</xref>. Dos 259 pacientes encaminhados ao TI, 28 (11%) apresentaram MSC+ a 60&#186; e a zero grau apenas em tr&#234;s. Nenhum participante apresentou complica&#231;&#245;es da MSC e do TI, o que vai ao encontro da seguran&#231;a reportada do teste<sup>14</sup>.</p>
    <table-wrap id="tab1">
      <graphic xlink:href="1678-4170-abc-90-04-0288-00009-gt01.jpg"/></table-wrap>
    <p>
      <bold>Pacientes</bold>
    </p>
    <p>Quando comparados aos pacientes MSC-, o grupo de pacientes MSC+ se constituiu predominantemente de homens idosos. Embora o TI tenha sido positivo em mais de dois ter&#231;os (71%) destes &#250;ltimos, essa propor&#231;&#227;o n&#227;o diferiu estatisticamente da observada nos pacientes MSC- (<italic>p</italic> = 0,53)</p>
    <p>Para explorar as associa&#231;&#245;es <italic>cl&#237;nicas da HSC</italic>, procedemos a regress&#245;es log&#237;sticas binomiais computando a MSC (MSC+ vs. MSC-) como vari&#225;vel dependente e, como vari&#225;veis independentes, idade, sexo, hist&#243;ria de desmaios (pacientes vs. controles), resultado do TI (positivo vs. normal) e &#237;ndices hemodin&#226;micos (press&#227;o arterial e freq&#252;&#234;ncia card&#237;aca). Houve correla&#231;&#227;o significativa entre o conjunto de vari&#225;veis e a ocorr&#234;ncia de HSC (R<sup>2</sup> = 0,47, <italic>p</italic> &lt; 0,001). A HSC foi prevista por sexo masculino (<bold>OR</bold> = 5,19, <italic>p</italic> &lt; 0,02), idade avan&#231;ada (<bold>OR</bold> = 1,10, <italic>p</italic> &lt; 0,001) e menor freq&#252;&#234;ncia card&#237;aca durante o TI no grupo com MSC+ (<bold>OR</bold> = 0,96, <italic>p</italic> &lt; 0,04). Esses resultados n&#227;o se modificaram qualitativamente ap&#243;s remo&#231;&#227;o dos controles da planilha de c&#225;lculo.</p>
    <p>Em an&#225;lise subseq&#252;ente, verificamos o resultado da MSC apenas nos pacientes com mais de 60 anos de idade (n = 138). Nesse subgrupo, a MSC foi positiva em 27, ou 19% (20 homens), e negativa em 111, ou 81% (32 homens). Como antecipado, n&#227;o houve diferen&#231;a estat&#237;stica de idade entre os grupos (<italic>U</italic> = 1411, <italic>p</italic> &gt; 0,64), mas a predomin&#226;ncia masculina de HSC foi reafirmada (c<sup>2</sup> = 19, <italic>p</italic> &lt; 0,001).</p>
    <p>
      <bold>Controles</bold>
    </p>
    <p>No grupo controle, a MSC a 60&#186; foi positiva em quatro homens com idade mediana de 70 anos. O predom&#237;nio masculino foi significativo nesse grupo em rela&#231;&#227;o aos demais controles (<italic>p</italic> = 0,02), e, embora as idades n&#227;o diferissem (<italic>U</italic> = 73, <italic>p</italic> &gt; 0,45), esse grupo tamb&#233;m mostrou tend&#234;ncia a menor freq&#252;&#234;ncia card&#237;aca basal durante o TI (medianas: 62 bpm x 70 bpm (<italic>U</italic> = 41,5, <italic>p</italic> &lt; 0,07)). O TI foi positivo em apenas tr&#234;s controles (&lt; 6%), nenhum dos quais apresentou HSC. Em rela&#231;&#227;o aos controles, a positividade do TI foi significativamente maior nos pacientes com HSC (c<sup>2</sup> = 35, <italic>p</italic> &lt; 0,001).</p>
    <p>
      <bold>Discuss&#227;o </bold>
    </p>
    <p>Os principais resultados do estudo podem ser assim resumidos: a) dentre os pacientes com desmaios, o TI n&#227;o diferiu naqueles com e sem HSC; b) estatisticamente, a freq&#252;&#234;ncia de HSC n&#227;o diferiu entre pacientes e controles; c) a propens&#227;o &#224; HSC nos homens idosos relacionou-se, estatisticamente, &#224; idade avan&#231;ada e ao sexo masculino; d) a aplica&#231;&#227;o da MSC a zero grau pode ser dispensada em favor da aplica&#231;&#227;o da MSC a 60&#186;.</p>
    <p>
      <bold>Import&#226;ncia da MSC no diagn&#243;stico da HSC</bold>
    </p>
    <p>Nossos achados enfatizam a import&#226;ncia da realiza&#231;&#227;o da MSC a 60&#186; no diagn&#243;stico da HSC: em 259 pacientes com hist&#243;ria de desmaios ou quedas inexplicadas, 28 (11%) apresentaram HSC &#224; inclina&#231;&#227;o de 60&#186;. Destes, em apenas tr&#234;s a resposta foi positiva a 0&#186;. Em contraste, apenas quatro controles apresentaram HSC. Curiosamente, a HSC n&#227;o foi maior no grupo com hist&#243;ria de desmaios em rela&#231;&#227;o aos controles. Embora os quatro indiv&#237;duos do grupo controle com HSC pudessem vir a apresentar desmaios se acompanhados por tempo suficiente, por ora podemos apenas sugerir que a utilidade diagn&#243;stica da MSC+ deve se restringir &#224;queles indiv&#237;duos com hist&#243;ria de desmaios claramente relacionados a manipula&#231;&#245;es cervicais. A relev&#226;ncia da HSC &#233; maior quando coincide com hist&#243;ria de desmaios ou quedas precipitadas por manipula&#231;&#245;es cervicais na vida real. Infelizmente, o nexo causal entre posi&#231;&#227;o da cabe&#231;a e s&#237;ncope fica nublado pela amn&#233;sia transit&#243;ria que acomete alguns desses pacientes<sup>15</sup>. Estudo recente em 80 indiv&#237;duos assintom&#225;ticos com mais de 65 anos constatou HSC em 28 (35%) deles<sup>16</sup>. A discrep&#226;ncia entre este resultado e o do presente estudo provavelmente se deve &#224; idade m&#233;dia mais baixa e &#224; maior preval&#234;ncia de mulheres nos nossos controles. Embora nossos resultados e os de v&#225;rios outros estudos concordem que a HSC &#233; ocorr&#234;ncia relativamente freq&#252;ente em indiv&#237;duos que nunca desmaiaram, o significado exato desse fen&#244;meno apenas ser&#225; esclarecido por estudos prospectivos que determinem a incid&#234;ncia de desmaios com a passagem do tempo. Por enquanto, a MSC+ na aus&#234;ncia de hist&#243;ria de desmaio ou queda det&#233;m significado cl&#237;nico incerto<sup>2,15</sup>.</p>
    <p>
      <bold>Teste inclinado e MSC</bold>
    </p>
    <p>A positividade do TI n&#227;o diferiu entre pacientes com e sem HSC, isto &#233;, o TI n&#227;o substituiu a MSC a 60&#186; no diagn&#243;stico da HSC. Do ponto de vista pr&#225;tico, se a MSC n&#227;o fosse realizada nos 8 indiv&#237;duos com desmaios e TI negativo, o diagn&#243;stico de HSC passaria despercebido. Al&#233;m disso, os pacientes com HSC e TI negativo indicam a opera&#231;&#227;o de mecanismos fisiopatol&#243;gicos distintos na produ&#231;&#227;o da s&#237;ncope.</p>
    <p>De fato, os mecanismos fisiopatol&#243;gicos exatos que levam &#224; falha intermitente dos reflexos cardiovasculares no dia-a-dia dos pacientes com HSC ainda n&#227;o foram completamente esclarecidos. Nesse sentido, uma constata&#231;&#227;o fisiopatol&#243;gica potencialmente relevante foi a menor FC <italic>durante</italic> o TI nos pacientes com HSC, sugestiva de falha nos reflexos baroceptores. Esses reflexos, cuja fisiologia &#233; hoje bem conhecida<sup>2</sup>, s&#227;o integrados por fibras que chegam pelos nervos glossofar&#237;ngeos aos n&#250;cleos vegetativos da forma&#231;&#227;o reticular do bulbo, de onde emanam fibras vagais e ret&#237;culo-espinhais para a coluna simp&#225;tica da medula tor&#225;cica<sup>17</sup>. Novos estudos s&#227;o necess&#225;rios para esclarecer os segmentos alterados desse circuito que comprometem a resposta cronotr&#243;pica nos pacientes com HSC.</p>
    <p>
      <bold>Contribui&#231;&#227;o da MSC para a economia diagn&#243;stica</bold>
    </p>
    <p>A maior parte dos pacientes com HSC havia consultado generalistas e especialistas antes que o TI fosse solicitado. &#201; prov&#225;vel que a imprevisibilidade e a raridade dos desmaios tenham contribu&#237;do para retardar o diagn&#243;stico de HSC. A m&#233;dia de quatro desmaios, aparentemente pequena em n&#250;mero absoluto, n&#227;o deve subestimar a elevada morbidade associada a uma &#250;nica queda, principalmente em pessoas idosas<sup>18</sup>. Al&#233;m disso, o atraso no diagn&#243;stico implica custos freq&#252;entemente desnecess&#225;rios. Por exemplo, se os pacientes encaminhados a parecer de especialista (cardiologista ou neurologista), eletrocardiograma e ecocardiograma, Holter, EEG, ecodoppler de car&#243;tidas e vertebrais, e pelo menos um exame de imagem cerebral (tomografia computadorizada ou resson&#226;ncia magn&#233;tica) houvessem sido submetidos no in&#237;cio &#224; MSC, o custo diagn&#243;stico seria substancialmente menor. Aparentemente, tal n&#227;o ocorreu por falta de uma estrat&#233;gia diagn&#243;stica guiada pela hip&#243;tese de HSC nesses casos.</p>
    <p>Ainda do ponto de vista econ&#244;mico, a HSC encerra implica&#231;&#245;es adicionais para a condu&#231;&#227;o de ve&#237;culos automotores<sup>19</sup>, pois, em raz&#227;o do mecanismo de deflagra&#231;&#227;o dos desmaios nesses casos, essa modalidade de s&#237;ncope pode acometer o indiv&#237;duo sentado ao volante, em movimentos da cabe&#231;a que comprimam um dos seios carot&#237;deos anormalmente sens&#237;vel.</p>
    <p>
      <bold>Agradecimentos </bold>
    </p>
    <p>Os autores agradecem ao Professor Omar da Rosa Santos (Hospital Universit&#225;rio Gaffr&#233; e Guinle, Rio de Janeiro) pelo apoio institucional e ao Srs. Jos&#233; Ricardo Pinheiro e Jorge Ba&#231;al (Instituto Oswaldo Cruz, Rio de Janeiro) pela sua inestim&#225;vel ajuda na pesquisa da literatura pertinente. Esse estudo deve muito &#224; inspira&#231;&#227;o intelectual do Sr. Emilio Sunda, atualmente no <italic>Physiological Department of the University of Manchester, UK.</italic></p>
    <p>
      <bold>Potencial Conflito de Interesses</bold>
    </p>
    <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
    <p>
      <bold>Fontes de Financiamento</bold>
    </p>
    <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
    <p>
      <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
    </p>
    <p>N&#227;o h&#225; vincula&#231;&#227;o acad&#234;mica deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
    <p>
      <fn id="end" fn-type="corresp">
        <p>Correspond&#234;ncia:</p>
        <p> Marcos Benchimol </p>
        <p> Rua Senador Dantas, 07/601 - Centro </p>
        <p> 20031-202 - Rio de Janeiro, RJ - Brasil </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="benchimol@cardiol.br">benchimol@cardiol.br</email>
        </p>
      </fn>
    </p>
    <p>Artigo recebido em 09/06/07; revisado recebido em 13/09/07; aceito em 30/10/07.</p>
  </body>
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              <surname>Tinetti</surname>
              <given-names>ME</given-names>
            </name>
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        </element-citation>
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        <mixed-citation>19. Li H, Weitzel M, Easley A, Barrington W, Windle J. Potential risk of vasovagal syncope for motor vehicle driving. Am J Cardiol. 2000; 85: 184-6.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Potential risk of vasovagal syncope for motor vehicle driving</article-title>
          <source>Am J Cardiol</source>
          <date>
            <year>2000</year>
          </date>
          <fpage>184</fpage>
          <lpage>6</lpage>
          <volume>85</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Li</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Weitzel</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Easley</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Barrington</surname>
              <given-names>W</given-names>
            </name>
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              <surname>Windle</surname>
              <given-names>J</given-names>
            </name>
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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">Diagnostic relevance of the carotid sinus massage during a head up tilt table test (HUTT)</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>BACKGROUND: Syncope due to carotid sinus hypersensitivity (CSH) may be underdiagnosed due to a low level of diagnostic suspicion and fear of complications caused by massage of the carotid sinus. OBJECTIVE: To investigate the relevance of carotid sinus massage in the diagnosis of non-convulsive faints and unexplained falls. METHODS: Two-hundred and fifty-nine patients with a mean age of 50&#177;24 years referred for the investigation of non-convulsive faints or unexplained falls were evaluated with a head up tilt table test (HUTT) without ("passive") and with pharmacological stimulation. Clinical and laboratory work-up did not reveal an obvious cause for the complaints. Fifty-five volunteers with a mean age of 57&#177;21 years with no history of seizures, faints or falls were used as controls. All participants underwent a HUTT preceded by digital stimulation of each carotid sinus both at zero and 60&#186;. RESULTS: Carotid sinus massage was positive in 4 controls. The relevance of CSH in the evaluation of syncope was supported by a positive response to carotid sinus massage at 60&#186; in 28 patients, most of whom were elderly men. Carotid sinus massage was positive at 0&#186; in only three of such patients. The results of the HUTT did not show statistical difference between patients with and without CSH. CONCLUSION: Carotid sinus massage at 60&#186; under controlled conditions should be included in the assessment of patients with non-convulsive faints or unexplained falls. Routine cardiovascular exams, including the HUTT, are not useful for the diagnosis in such cases. Further studies in normal individuals are needed to establish the significance of a positive response to carotid sinus massage in the absence of a history of fainting or falling.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Syncope</kwd>
        <kwd>hypersensitivity</kwd>
        <kwd>carotid sinus</kwd>
        <kwd>tilt table test</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ORIGINAL ARTICLE</bold>
      </p>
      <p><undefined id="tit-body2"/>Diagnostic relevance of the carotid sinus massage during a head up tilt table test (HUTT)</p>
      <p>
        <bold>Marcos Benchimol<sup>I,II</sup>; Ricardo Oliveira-Souza<sup>I</sup></bold>
      </p>
      <p><sup>I</sup>Universidade Federal do Estado do Rio de Janeiro (UNI-RIO)</p>
      <p><sup>II</sup>Cl&#237;nica Benchimol, Rio de Janeiro, RJ - Brazil</p>
      <p>Mailing address</p>
      <p>
        <bold>SUMMARY</bold>
      </p>
      <p><bold>BACKGROUND:</bold> Syncope due to carotid sinus hypersensitivity (CSH) may be underdiagnosed due to a low level of diagnostic suspicion and fear of complications caused by massage of the carotid sinus.</p>
      <p><bold>OBJECTIVE:</bold> To investigate the relevance of carotid sinus massage in the diagnosis of non-convulsive faints and unexplained falls.</p>
      <p><bold>METHODS:</bold> Two-hundred and fifty-nine patients with a mean age of 50&#177;24 years referred for the investigation of non-convulsive faints or unexplained falls were evaluated with a head up tilt table test (HUTT) without ("passive") and with pharmacological stimulation. Clinical and laboratory work-up did not reveal an obvious cause for the complaints. Fifty-five volunteers with a mean age of 57&#177;21 years with no history of seizures, faints or falls were used as controls. All participants underwent a HUTT preceded by digital stimulation of each carotid sinus both at zero and 60&#186;.</p>
      <p><bold>RESULTS:</bold> Carotid sinus massage was positive in 4 controls. The relevance of CSH in the evaluation of syncope was supported by a positive response to carotid sinus massage at 60&#186; in 28 patients, most of whom were elderly men. Carotid sinus massage was positive at 0&#186; in only three of such patients. The results of the HUTT did not show statistical difference between patients with and without CSH.</p>
      <p><bold>CONCLUSION:</bold> Carotid sinus massage at 60&#186; under controlled conditions should be included in the assessment of patients with non-convulsive faints or unexplained falls. Routine cardiovascular exams, including the HUTT, are not useful for the diagnosis in such cases. Further studies in normal individuals are needed to establish the significance of a positive response to carotid sinus massage in the absence of a history of fainting or falling.</p>
      <p><bold>Key words: </bold>Syncope; hypersensitivity; carotid sinus; tilt table test.</p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p>The original description of convulsive syncope due to carotid sinus massage was also the first one to correctly interpret bradycardia and hypotension as abnormal <italic>reflex</italic> responses and its normalization by previous atropine use<sup>1</sup>. Currently, the carotid sinus <italic>hypersensitivity</italic> (CSH) is diagnosed in patients in whom the carotid sinus massage (CSM) induces asystole for more than 3 seconds (cardioinhibitory type) <italic>or</italic> systolic pressure decrease &gt; 50 mmHg (vasodepressor type)<sup>2</sup>. Subsequent studies established the importance of CSM as the cause of fainting<sup>3</sup> and drop attacks<sup>4</sup>, as well as the increase in the reflex reactivity of the carotid sinus that occurs with aging, mainly in men<sup>5</sup>. The inclusion of the Head-up Tilt Table Test (HUTT)<sup>6</sup> increased the extent of causes of neurocardiogenic syncopes, particularly those caused by CSH<sup>7</sup>. </p>
      <p>However, despite the increasing number of studies that used CSM under controlled positions, the clinical significance of CSH remains to be clarified, especially considering its unexpectedly high prevalence among individuals that have never fainted<sup>8</sup>. The main objectives of the present study were: (i) to report on a series of individuals referred to a HUTT to investigate non-convulsive faints or unexplained falls; (ii) to determine the prevalence of induced CSH induced by CSM in this series of patients and (iii) to determine the usefulness of the HUTT used in our Service based on a group of volunteers with no history of unexplained falls or fainting.</p>
      <p>
        <bold>Methods</bold>
      </p>
      <p>One hundred and seventy women and 89 men aged 10 to 96 years (mean age = 50 &#177; 24 yrs) were referred for the investigation of "fainting" or unexplained falls (drop attacks) of which the first episode had occurred several months before (mean period = 53 &#177; 100 months). Nineteen patients with +CSM had been regularly using benzodiazepines (n=2), anticonvulsants (n=3), hypotensive drugs (n=15), diuretics (n=5) and oral anticoagulants (n=1). The physical examination, ECG and echocardiogram were either normal or showed no association with the symptoms of interest. Fifty-five volunteers (32 women, 23 men) with no history of unexplained falls or fainting, aged 16 to 88 years (mean age = 57 &#177; 21 yrs) served as controls for the HUTT. There was no difference regarding age between men and women in the patients' group (<italic>U</italic> = 5200, <italic>p</italic> &gt; 0.56) or controls (<italic>U</italic> = 329, <italic>p</italic> &gt; 0.98). Additionally, there was no difference between the groups regarding the gender composition (c<sup>2</sup> = 0.77, <italic>p</italic> &gt; 0.38). All patients and controls signed an informed consent form prior to enrollment in the study, which was approved by the Institutional Ethics Committee of <italic>Hospital Universit&#225;rio Gaffr&#233;e e Guinle</italic>.</p>
      <p>
        <bold>HUTT and CSM</bold>
      </p>
      <p>The HUTT was performed between 2 and 5 PM<sup>9</sup> in a quiet room, under soft lights and comfortable room temperature, according to the broadly accepted technical recommendations<sup>10</sup>. The test table (Carci, S&#227;o Paulo, Brazil), was equipped with a TEB system for continuous ECG monitoring and support for the feet and allowed 60 to 80&#186; inclinations. Blood pressure was measured by an oscillometer and the levels were confirmed by a sphygmomanometer at regular intervals. A resuscitation tray was kept at hand throughout the test. Each individual was asked to fast for 12 hours and, if possible, to withdraw medications for 24 hours prior to the test. After 10 minutes of resting on dorsal decubitus, the examiner manually massaged the region of the neck where the carotid pulse attained maximum intensity, for 5 seconds, usually on the upper border of the cricoid cartilage, starting on the right side. Subsequently, the table was tilted at 60&#186; and the maneuver was repeated on each side. Previous observations showed that the carotid sinus massage can be completely normal at 0&#186; and become positive only after the tilting<sup>11</sup>. The HUTT consisted of two conditions<sup>10</sup>: (i) a "passive" condition (<italic>i.e</italic>., without pharmacological intervention) and (ii) a pharmacologically "sensitized" condition that consisted in administering 1.25 mg of isosorbide dinitrate by sublingual route in order to cause unapparent symptoms in the passive condition. Each condition lasted 25 minutes or less, in case of pre-syncope. When the test was positive in the first phase, it was concluded without the need to perform the sensitized condition. The HUTT was normally performed in cases of positive CSM. The HUTT was considered abnormal ("positive") if syncopal or pre-syncopal symptoms mediated by neural mechanisms occurred due to hypotension, bradycardia or both, whether the individual attested or not the replication of symptoms that affected him/her in real life. The CSM was considered positive if there was a minimum decrease of 50 mmHg in the systolic blood pressure or bradycardia/asystole<sup>2,10</sup>. Carotid murmur, cerebrovascular accidents or acute myocardial infarction in the six months prior to the test or previous history of severe ventricular arrhythmia were contraindications for the test. </p>
      <p>
        <bold>Statistical analysis of the results</bold>
      </p>
      <p>The results are shown as means &#177; standard deviations. Possible associations between categorical variables were inferred by the Chi-square (c<sup>2</sup>) test. The significance of the differences between groups was measured by the Mann-Whitney test (<italic>U)</italic> and Fisher Exact test<sup>12</sup>. The relative contribution of age, sex, HUTT result and physiological indexes (blood pressure and heart rate) for the occurrence of CSH was inferred by Binomial Logistic Regression. The Binomial Logistic Regression is appropriate for dichotomous dependent variables (such as +CSM <italic>vs</italic> -CSM), to which a value equal to 1 is attributed to the main interest variable (for instance, +CSM) and zero to the other (for instance, -CSM). The size of the effect and the direction of the association between the independent variables are expressed as odds ratio (<bold>OR</bold>). </p>
      <p>Each <bold>OR</bold> can vary from zero to 0.999 (in the case of an inverse relation) or from1.001 to infinite (in the case of a direct relation); when the <bold>OR</bold> = 1, the variables are statistically independent<sup>13</sup>. The size of the global effect of the logistic regression was measured by Nagelkerke's R<sup>2</sup>, which, similarly to the multiple determination coefficient (R<sup>2</sup>), varies from zero to 1. Statistical significance level was set at 0.05 (two-tailed), for all statistical tests. Calculations were carried out using the spss for Windows, v. 13.0 (<bold>SPSS</bold> Inc, 2004).</p>
      <p>
        <bold>Results</bold>
      </p>
      <p>The main results are shown in <xref ref-type="table" rid="tab1-body2">Table 1</xref>. Of the 259 patients referred to HUTT, 28 (11%) presented +CSM at 60&#186; and only 3 at 0&#186;. No participant presented complications caused by the CSM or HUTT, which is in agreement with the reported safety of the test<sup>14</sup>.</p>
      <table-wrap id="tab1-body2">
        <graphic xlink:href="1678-4170-abc-90-04-0288-00009-gt01-en.jpg"/></table-wrap>
      <p>
        <bold>Patients</bold>
      </p>
      <p>When compared to the &#150;CSM patients, the +CSM group consisted mainly of elderly men. Although the HUTT was positive in more than two-thirds (71%) of the latter, this percentage did not statistically differ from that observed in &#150;CSM patients (<italic>p</italic> = 0.53).</p>
      <p>To explore the clinical associations of the CSH, the binomial logistic regressions were carried out, considering the CSM (+CSM <italic>vs</italic>. &#150;CSM) as a dependent variable and age, sex, history of fainting (patients <italic>vs</italic>. controls), HUTT result (positive <italic>vs</italic>. normal) and hemodynamic indexes (blood pressure and heart rate) as independent variables. There was a significant correlation between the set of variables and the occurrence of CSH (R<sup>2</sup> = 0.47, <italic>p</italic> &lt; 0.001). The CSH was predicted by male sex (or = 5.19, <italic>p</italic> &lt; 0.02), older age (or = 1.10, <italic>p</italic> &lt; 0.001), and lower heart rate during HUTT in the group with +CSM (or = 0.96, <italic>p</italic> &lt; 0.04). These results were not qualitatively modified after removing the controls from the calculation spreadsheets. </p>
      <p> At a subsequent analysis, the result of the CSM was verified only in patients older than 60 years (n=138). In this subgroup, CSM was positive in 27 or 19% of the patients (20 men) and negative in 111 or 81% (32 men). As anticipated, there was no statistical difference regarding the age between the groups <italic>(U</italic> = 1411, <italic>p</italic> &gt; 0.64), but the male predominance of CSH was confirmed (c<sup>2</sup> = 19, <italic>p</italic> &lt; 0.001).</p>
      <p>
        <bold>Controls</bold>
      </p>
      <p>In the control group, the CSM at 60&#186; was positive in four men with a median age of 70 years. The male predominance was significant in this group in relation to the other controls (<italic>p</italic> = 0.02) and, although there was no difference regarding the age <italic>(U</italic> = 73, <italic>p</italic> &gt; 0.45), this group also showed a tendency to present lower basal heart rate during HUTT [medians: 62 bpm x 70 bpm (<italic>U</italic> = 41.5, <italic>p</italic> &lt; 0.07)]. </p>
      <p>The HUTT was positive in only 3 controls (&lt; 6%), none of which presented CSH. Regarding the controls, positivity at the HUTT was significantly higher in patients with CSH (c<sup>2</sup> = 35, <italic>p</italic> &lt; 0.001).</p>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>The main results of the study can be thus summarized: (a) among patients with a history of fainting, the HUTT did not differ between those with and without CSH; (b) statistically, the frequency of CSH did not differ between patients and controls; (c) the tendency to CSH in elderly men was statistically correlated with older age and male sex; (d) the CSM at 0&#186; can be dispensed with in favor of the one at 60&#186;.</p>
      <p>
        <bold>Importance of CSM in the diagnosis of CSH</bold>
      </p>
      <p>Our findings emphasize the importance of performing the CSM at 60&#186; in the diagnosis of CSH: of 259 patients with a history of fainting or unexplained falls, 28 (11%) presented CSH at 60&#186; inclination. Of these, only three presented a positive response at 0&#186;. In contrast, only 4 controls presented CSH. Interestingly, CSH was not higher in the group with a history of fainting in relation to controls. Although the four individuals from the control group with CSH could present fainting episodes if followed for a sufficient period of time, we can, at the moment, only suggest that the diagnosis usefulness of the +CSM must be restricted to those individuals with a history of fainting clearly related to cervical manipulations. The relevance of the CSH is higher when it coincides with a history of fainting or falls that are precipitated by cervical manipulations in real life. Unfortunately, the causal nexus between head position and syncope becomes blurred due to the transient amnesia that affects some of these patients<sup>15</sup>. A recent study in 80 asymptomatic individuals older than 65 years demonstrated CSH in 28 (35%) of them<sup>16</sup>. The discrepancy between these findings and those of the present study is probably due to the lower mean age and higher prevalence of women among our controls. Although our results and those of several other studies agree that CSH is a relatively frequent occurrence among individuals that never fainted, the exact meaning of this phenomenon will only be clarified by further prospective studies that will determine the incidence of fainting with the passing of time. For the time being, the +CSM in the absence of fainting or falls has an unclear clinical significance<sup>2,15</sup>.</p>
      <p>
        <bold>HUTT and CSM</bold>
      </p>
      <p> The HUTT positivity did not differ between patients with and without CSH; i.e., the HUTT did not substitute the CSM at 60&#186; in the diagnosis of CSH. From a practical point of view, if the CSM had not been performed in the 8 individuals who presented fainting and negative HUTT, the diagnosis of CSH would have been missed. Additionally, the patients with CSH and negative HUTT demonstrate the existence of distinct physiopathological mechanisms in the syncope event. </p>
      <p>In fact, the exact physiopathological mechanisms that lead to the intermittent failure of the cardiovascular reflexes in the daily life of patients with CSH have yet to be completely clarified. In this sense, a potentially relevant physiopathological observation was the lower HR <italic>during</italic> HUTT in patients with CSH, which is suggestive of baroreceptor reflex failure. These reflexes, of which physiology is currently well known<sup>2</sup>, are integrated by fibers that reach, through the glossopharyngeal nerves, the vegetative nuclei of the reticular formation of the bulb, from where the vagal and reticulospinal fibers radiate to the sympathetic column of the thoracic spinal cord<sup>17</sup>. </p>
      <p>Further studies are necessary to clarify the altered segments of this circuit that impair the chronotropic response in patients with CSH.</p>
      <p>
        <bold>Contribution of CSM to diagnostic economy</bold>
      </p>
      <p>Most of the patients with CSH had been seen by general practitioners and specialists before the HUTT was requested. It is likely that the unpredictability and rarity of the faints contributed to delay the diagnosis of CSH. The mean of four fainting episodes, apparently low in absolute numbers, must not underestimate the high morbidity associated to a single fall, especially among elderly patients<sup>18</sup>. Additionally, the diagnosis delay implicates in frequently unnecessary costs. For instance, if the patients referred to a specialist's assessment (cardiologist or neurologist), electrocardiogram and echocardiogram, Holter monitoring, EEG, echo Doppler of the carotid and vertebral arteries and at least one brain imaging assessment (computed tomography or magnetic resonance) had been initially submitted to CSM, the diagnostic cost would have been substantially lower. Apparently, such has not occurred due to the lack of diagnostic strategy guided by the hypothesis of CSH in these cases. </p>
      <p>Also from an economical point of view, the CSH presents additional implications for automobile driving<sup>19</sup>, considering that, due to the mechanism that triggers fainting in these cases, this type of syncope can affect the individual while driving, during head movements that compress one of the abnormally sensitive carotid sinuses.</p>
      <p>
        <bold>Acknowledgments</bold>
      </p>
      <p>The authors are indebted to Professor Omar da Rosa Santos (Gaffr&#233; and Guinle University Hospital, Rio de Janeiro) for institutional support and to Mr. Jos&#233; Ricardo Pinheiro and Mr. Jorge Ba&#231;al (<italic>Instituto Oswaldo Cruz</italic>, Rio de Janeiro) for their invaluable assistance in the retrieval of the pertinent literature. This study owes much to the intellectual inspiration of Mr. Emilio Sunda, presently at the Physiological Department of the University of Manchester, UK.</p>
      <p>
        <bold>Potential Conflict of Interest</bold>
      </p>
      <p>No potential conflict of interest relevant to this article was reported.</p>
      <p>
        <bold>Sources of Funding</bold>
      </p>
      <p>There were no external funding sources for this study.</p>
      <p>
        <bold>Study Association</bold>
      </p>
      <p>This study is not associated with any graduation program.</p>
      <p>
        <bold>References</bold>
      </p>
    </body>
  </sub-article>
</article>
