<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.1 20151215//EN" "https://jats.nlm.nih.gov/publishing/1.1/JATS-journalpublishing1.dtd">
<article xmlns:xlink="http://www.w3.org/1999/xlink" specific-use="sps-1.9" dtd-version="1.1" xml:lang="pt" article-type="research-article">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
        <publisher-loc>S&#227;o Paulo, SP, Brazil</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">w5ZJKgG38ZnTqyyq8FMvn9m</article-id>
      <article-id pub-id-type="other">00004</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2006000100004</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(06)08600104</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2006000100004</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Estudos eletrofisiol&#243;gicos seriados do sistema &#233;xcito-condutor do cora&#231;&#227;o de pacientes com cardiopatia chag&#225;sica cr&#244;nica</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Valente</surname>
            <given-names>Ney</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pimenta</surname>
            <given-names>Jo&#227;o</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Paola</surname>
            <given-names>Angelo Amato Vincenzo de</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
      </contrib-group>
      <aff id="aff02">
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">S&#227;o Paulo</named-content>
        </addr-line>
        <institution content-type="orgname">Universidade Federal de S&#227;o Paulo</institution>
        <country country="BR">Brazil</country>
      </aff>
      <aff id="aff01">
        <institution content-type="orgname">Hospital do Servidor P&#250;blico Estadual</institution>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>01</month>
        <year>2006</year>
      </pub-date>
      <volume>86</volume>
      <issue>1</issue>
      <fpage>19</fpage>
      <lpage>25</lpage>
      <history>
        <date date-type="received">
          <day>18</day>
          <month>05</month>
          <year>2005</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>OBJETIVOS:Estudar a evolu&#231;&#227;o das les&#245;es do sistema de condu&#231;&#227;o do cora&#231;&#227;o, por meio de estudos eletrofisiol&#243;gicos (EEF) invasivos, o impacto dessas altera&#231;&#245;es nos eventos cardiovasculares (ECV) e a freq&#252;&#234;ncia desses eventos em pacientes com cardiopatia chag&#225;sica cr&#244;nica. M&#201;TODOS: Estudo prospectivo iniciado em 1979, com seguimento cl&#237;nico at&#233; 2000, com participa&#231;&#227;o de 28 pacientes chag&#225;sicos cr&#244;nicos, com idade entre 18 e 65 anos, portadores de bloqueios de ramo e/ou bloqueios atrioventriculares (AV). Os pacientes foram submetidos a dois EEF, com intervalo de tempo m&#237;nimo de 4 anos, sendo estudados 5 par&#226;metros eletrofisiol&#243;gicos, que foram correlacionados com ECV. Holter de 24 horas e ecocardiograma foram realizados. RESULTADOS: O tempo m&#233;dio de seguimento ap&#243;s o 1&#186; EEF foi de 154,5 meses, enquanto o intervalo entre os EEF foi de 107,5 meses. A idade variou entre 25 e 65 anos. Vinte e sete pacientes apresentavam bloqueio completo de ramo direito, associado ou n&#227;o a bloqueio divisional &#226;ntero-superior esquerdo. O ecocardiograma foi alterado em 12 pacientes. Ao Holter de 24 horas e &#224; estimula&#231;&#227;o ventricular, apenas um paciente apresentou TVS. Nove apresentaram ECV e somente o intervalo HV &gt;70 ms apresentou rela&#231;&#227;o estatisticamente significante com esses eventos. CONCLUS&#213;ES: a) A forma cr&#244;nica da doen&#231;a de Chagas apresenta diferentes porcentagens de anormalidades evolutivas nas vari&#225;veis eletrofisiol&#243;gicas, sendo a mais freq&#252;ente a altera&#231;&#227;o no PW. b) Entre os achados eletrofisiol&#243;gicos, somente o intervalo HV &gt; 70 ms relacionou-se com ECV. c) A incid&#234;ncia de ECV foi de 31,1% seguimento m&#233;dio de 154,5 meses.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>estudo eletrofisiol&#243;gico</kwd>
        <kwd>eventos cardiovasculares</kwd>
        <kwd>doen&#231;a de Chagas</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>13</day>
        <month>02</month>
        <year>2006</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>ARTIGO ORIGINAL</bold>
    </p>
    <p>Estudos eletrofisiol&#243;gicos seriados do sistema &#233;xcito-condutor do cora&#231;&#227;o de pacientes com cardiopatia chag&#225;sica cr&#244;nica </p>
    <p>
      <bold>Ney Valente; Jo&#227;o Pimenta; Angelo Amato Vincenzo de Paola</bold>
    </p>
    <p>Hospital do Servidor P&#250;blico Estadual e Universidade Federal de S&#227;o Paulo - Unifesp - S&#227;o Paulo, SP</p>
    <p>
      <xref ref-type="corresp" rid="end">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>OBJETIVOS:</bold>Estudar a evolu&#231;&#227;o das les&#245;es do sistema de condu&#231;&#227;o do cora&#231;&#227;o, por meio de estudos eletrofisiol&#243;gicos (EEF) invasivos, o impacto dessas altera&#231;&#245;es nos eventos cardiovasculares (ECV) e a freq&#252;&#234;ncia desses eventos em pacientes com cardiopatia chag&#225;sica cr&#244;nica. </p>
    <p><bold>M&#201;TODOS: </bold>Estudo prospectivo iniciado em 1979, com seguimento cl&#237;nico at&#233; 2000, com participa&#231;&#227;o de 28 pacientes chag&#225;sicos cr&#244;nicos, com idade entre 18 e 65 anos, portadores de bloqueios de ramo e/ou bloqueios atrioventriculares (AV). Os pacientes foram submetidos a dois EEF, com intervalo de tempo m&#237;nimo de 4 anos, sendo estudados 5 par&#226;metros eletrofisiol&#243;gicos, que foram correlacionados com ECV. Holter de 24 horas e ecocardiograma foram realizados. </p>
    <p><bold>RESULTADOS: </bold>O tempo m&#233;dio de seguimento ap&#243;s o 1&#186; EEF foi de 154,5 meses, enquanto o intervalo entre os EEF foi de 107,5 meses. A idade variou entre 25 e 65 anos. Vinte e sete pacientes apresentavam bloqueio completo de ramo direito, associado ou n&#227;o a bloqueio divisional &#226;ntero-superior esquerdo. O ecocardiograma foi alterado em 12 pacientes. Ao Holter de 24 horas e &#224; estimula&#231;&#227;o ventricular, apenas um paciente apresentou TVS. Nove apresentaram ECV e somente o intervalo HV &gt;70 ms apresentou rela&#231;&#227;o estatisticamente significante com esses eventos. </p>
    <p><bold>CONCLUS&#213;ES: </bold>a) A forma cr&#244;nica da doen&#231;a de Chagas apresenta diferentes porcentagens de anormalidades evolutivas nas vari&#225;veis eletrofisiol&#243;gicas, sendo a mais freq&#252;ente a altera&#231;&#227;o no PW. b) Entre os achados eletrofisiol&#243;gicos, somente o intervalo HV <underline>&gt;</underline> 70 ms relacionou-se com ECV. c) A incid&#234;ncia de ECV foi de 31,1% seguimento m&#233;dio de 154,5 meses.</p>
    <p><bold>Palavras-chave:</bold> estudo eletrofisiol&#243;gico, eventos cardiovasculares, doen&#231;a de Chagas</p>
    <p>Na doen&#231;a de Chagas, eventos cardiovasculares (ECV) como taquicardia ventricular sustentada (TVS), morte s&#250;bita (MS), tromboembolismo e morte card&#237;aca tardia (MCT) t&#234;m sido amplamente estudados<sup>1-4</sup>. O eletrocardiograma (ECG) pode mostrar sinais de comprometimento mioc&#225;rdico significativo, como a presen&#231;a de bloqueio completo de ramo direito, associado ou n&#227;o a bloqueio da divis&#227;o &#226;ntero-superior esquerda. A presen&#231;a de &#225;reas inativas, bloqueio completo de ramo esquerdo, fibrila&#231;&#227;o atrial e taquiarritmias ventriculares indica pior prognose em raz&#227;o de extensa fibrose mioc&#225;rdica presente nessas situa&#231;&#245;es. </p>
    <p>O estudo eletrofisiol&#243;gico (EEF) e a angiografia do ventr&#237;culo esquerdo realizados em pacientes sintom&#225;ticos ou n&#227;o, e com ou sem dist&#250;rbios da condu&#231;&#227;o, mostraram pior evolu&#231;&#227;o em chag&#225;sicos cr&#244;nicos. Essa evolu&#231;&#227;o esteve relacionada com disfun&#231;&#227;o mioc&#225;rdica e, em menor propor&#231;&#227;o, pela presen&#231;a de dist&#250;rbios de condu&#231;&#227;o<sup>5</sup>, provavelmente pelo fato de a primeira estar associada &#224; presen&#231;a de arritmias ventriculares complexas<sup>6</sup>.</p>
    <p>V&#225;rios relatos de EEF repetidos em pacientes n&#227;o-chag&#225;sicos foram publicados, todos acompanhando as mudan&#231;as no sistema de condu&#231;&#227;o com intervalo m&#225;ximo de 35 meses entre os estudos<sup>7,8</sup>. Em rela&#231;&#227;o &#224; doen&#231;a de Chagas, n&#227;o se encontram trabalhos utilizando EEF repetidos no mesmo paciente, acompanhados por longo per&#237;odo de tempo e relacionando as altera&#231;&#245;es desse exame com ECV. O presente trabalho teve como objetivo estudar o comportamento evolutivo das les&#245;es do sistema &#233;xcito-condutor do cora&#231;&#227;o por meio de EEF invasivos, o impacto dessas altera&#231;&#245;es sobre os ECV e a freq&#252;&#234;ncia de ECV nesses pacientes seguidos em longo prazo. </p>
    <p>
      <bold>M&#201;TODOS</bold>
    </p>
    <p>Trata-se de um estudo prospectivo, aprovado pelo Comit&#234; de &#201;tica e Pesquisa da Institui&#231;&#227;o. Foram estudados 28 pacientes com as seguintes caracter&#237;sticas ao entrar no estudo: ter pelo menos duas provas sorol&#243;gicas positivas para a doen&#231;a de Chagas, idade entre dezoito e 65 anos, serem assintom&#225;ticos ou oligossintom&#225;ticos at&#233; a classe II da NYHA, sem outra cardiopatia pr&#233;via, com ECG alterado por bloqueio de ramo ou bloqueio atrioventricular, com radiografia de t&#243;rax mostrando &#225;rea card&#237;aca normal ou com aumento de at&#233; ++ (em 4+). Ecocardiograma foi realizado por ocasi&#227;o do 2&#186; EEF, sendo observadas a contratilidade mioc&#225;rdica e a fra&#231;&#227;o de eje&#231;&#227;o. A an&#225;lise da contratilidade mioc&#225;rdica era considerada alterada quando apresentava hipocontratilidade difusa ou segmentar de qualquer grau, e a fra&#231;&#227;o de eje&#231;&#227;o quando fosse inferior a 0,65. O Holter de 24 horas tamb&#233;m foi realizado junto ao 2&#186; EEF, com a finalidade de se detectar extra-s&#237;stoles ventriculares, TVS e TVNS. </p>
    <p>Todos os pacientes aceitaram, por escrito, se submeter ao EEF. O in&#237;cio do estudo correspondia &#224; data da primeira avalia&#231;&#227;o eletrofisiol&#243;gica e nenhum paciente fazia uso de medica&#231;&#227;o que pudesse alterar as medidas avaliadas. Foram realizados dois EEF com t&#233;cnicas j&#225; descritas, bem como seus valores normais<sup>9,10</sup>. Foram considerados elevados os valores que se apresentavam acima do normal no 1&#186; e 2&#186; EEF ou quando aumentavam do 1&#186; para o 2&#186; estudos. Os achados do intervalo HV foram subdivididos em maior ou igual e menores que 70 ms para avaliar um poss&#237;vel grupo de maior risco para ECV. Os valores elevados no 1&#186; estudo, que se normalizaram no 2&#186;, fato observado com o intervalo AH e com o PW pela flutua&#231;&#227;o vagal, foram considerados normais. </p>
    <p>Estimula&#231;&#227;o ventricular foi realizada em todos os pacientes com extra-est&#237;mulo at&#233; o per&#237;odo refrat&#225;rio. Holter de 24 horas e ecocardiograma foram realizados por ocasi&#227;o do 2&#186; EEF para observa&#231;&#227;o de arritmias e avalia&#231;&#227;o da fun&#231;&#227;o ventricular, respectivamente (<xref ref-type="table" rid="tab01">tabela 1</xref>). O seguimento ambulatorial era realizado a cada tr&#234;s ou seis meses, na depend&#234;ncia do aparecimento de sintomas. </p>
    <table-wrap id="tab01">
      <graphic xlink:href="1678-4170-abc-86-01-0019-00004-gt01.jpg"/></table-wrap>
    <p>A an&#225;lise estat&#237;stica foi realizada por meio do teste exato de Fisher, sendo considerado estatisticamente significante quando p &lt; 0,05. </p>
    <p>
      <bold>RESULTADOS</bold>
    </p>
    <p>A idade variou entre 25 e 65 anos, m&#233;dia de 42,3 anos e mediana de quarenta anos no 1&#186; EEF, e entre 34 e oitenta anos, com m&#233;dia de 52,2 anos, no 2&#186; EEF, sendo dezesseis do sexo masculino. Com exce&#231;&#227;o de um, todos os demais apresentavam bloqueio completo do ramo direito (BCRD), sendo associados a bloqueio divisional &#226;ntero-superior esquerdo (BDAS) em dezessete. Uma paciente, &#250;nica com complexos QRS normais, apresentava bloqueio AV de 2&#186; grau tipo I. O padr&#227;o eletrocardiogr&#225;fico n&#227;o se alterou na maioria dos pacientes durante o estudo, notando-se apenas mudan&#231;a para bloqueio AV total em dois deles, um com BCRD e o outro com BCRD associado a BDAS quando do 1&#186; EEF. Uma paciente que apresentava bloqueio AV de 2&#186; grau tipo I, sem dist&#250;rbio na condu&#231;&#227;o intraventricular, desenvolveu BCRD, sem piora do bloqueio AV. O intervalo m&#233;dio entre os estudos foi de 107,5 (50 a 199) meses e o tempo m&#233;dio de seguimento ap&#243;s o 1&#186; EEF foi de 154,5 (81 a 233) meses. </p>
    <p><italic><bold>Eventos cardiovasculares - </bold></italic>Foram observados em nove pacientes (31,1%), dos quais quatro tiveram MS, quatro acidente vascular cerebral isqu&#234;mico (AVCI), um TVS, um embolia pulmonar e tr&#234;s MCT. Um paciente apresentou AVCI e morte s&#250;bita, e aqueles com MCT tiveram outro evento adicional (embolia pulmonar, TVS e AVCI) precedendo o &#243;bito. Os dados obtidos no 1&#186; EEF e os ECV est&#227;o dispostos na <xref ref-type="table" rid="tab02">tabela 2</xref>, bem como a <xref ref-type="fig" rid="fig01">figura 1</xref> mostra as altera&#231;&#245;es do 1&#186; e do 2&#186; EEF e as respectivas propor&#231;&#245;es de aumento.</p>
    <table-wrap id="tab02">
      <graphic xlink:href="1678-4170-abc-86-01-0019-00004-gt02.jpg"/></table-wrap>
    <fig id="fig01">
      <graphic xlink:href="1678-4170-abc-86-01-0019-00004-gf01.jpg"/></fig>
    <p><italic><bold>Ecocardiograma</bold></italic> - A contratilidade mioc&#225;rdica foi normal em dezesseis pacientes e alterada em doze, com hipocinesia difusa em sete e segmentar em cinco. Destas, quatro eram inferobasais e uma &#226;ntero-apical (<xref ref-type="table" rid="tab01">tabela 1</xref>).</p>
    <p><italic><bold>Holter de 24 horas - </bold></italic>A presen&#231;a de TVS foi observada em somente um paciente e TVNS em nove. Extra-s&#237;stoles ventriculares &gt; 30/ h e &lt; 30/ h foram observadas em quatorze pacientes (<xref ref-type="table" rid="tab01">tabela 1</xref>).</p>
    <p><italic><bold>Estudo eletrofisiol&#243;gico - </bold></italic>Intervalo AH - Mostrou-se aumentado em cinco pacientes (17,8%), sendo quatro (14,2%) deles no 1&#186; estudo, e dois apresentaram ECV (NS). A propor&#231;&#227;o de novos aumentos do 1&#186; para o 2&#186; EEF foi de 4,16% (<xref ref-type="table" rid="tab02">tabela 2</xref>). </p>
    <p>Intervalo HV &#150; Observou-se aumento em seis pacientes (21,4%), sendo dois deles no 1&#186; estudo e quatro apresentaram ECV (NS). A propor&#231;&#227;o de novos aumentos do 1&#186; para o 2&#186; EEF foi de 15,38%. Cinco pacientes (17,8%) apresentaram intervalo HV <underline>&gt;</underline>70 ms, sendo quatro com ECV (p = 0,025) (<xref ref-type="table" rid="tab02">tabela 2</xref>). </p>
    <p>Tempo corrigido de recupera&#231;&#227;o do n&#243;dulo sinusal &#150; Esteve aumentado em seis pacientes (21,4%), tr&#234;s dos quais no 1&#186; estudo, sendo observado ECV em apenas um (NS). A propor&#231;&#227;o de novos aumentos do 1&#186; para o 2&#186; EEF foi de 12% (<xref ref-type="table" rid="tab02">tabela 2</xref>).</p>
    <p>Ponto de Wenckebach &#150; Mostrou-se aumentado em onze pacientes (39,2%) sendo sete no 1&#186; estudo, observando-se ECV em quatro (NS). A propor&#231;&#227;o de novos aumentos do 1&#186; para o 2&#186; EEF foi de 19,04% (<xref ref-type="table" rid="tab02">tabela 2</xref>).</p>
    <p>Altera&#231;&#227;o da curva de fun&#231;&#227;o do n&#243;dulo AV - Presente em seis pacientes (21,4%), sendo quatro deles (14,3%) no 1&#186; estudo, observando-se ECV em apenas um (NS). A propor&#231;&#227;o de novos casos com esta altera&#231;&#227;o foi de 8,3% (<xref ref-type="table" rid="tab02">tabela 2</xref>).</p>
    <p>Estimula&#231;&#227;o ventricular &#150; Observou-se TVS em um paciente e batimentos repetitivos em cinco (<xref ref-type="table" rid="tab02">tabela 2</xref>).</p>
    <p>
      <bold>DISCUSS&#195;O</bold>
    </p>
    <p>A cardiopatia chag&#225;sica cr&#244;nica com freq&#252;&#234;ncia apresenta evolu&#231;&#227;o prolongada, por&#233;m muitas vezes esta se torna abreviada pelo aparecimento de ECV. Tais complica&#231;&#245;es freq&#252;entemente se associam a um substrato histol&#243;gico, mostrando degenera&#231;&#227;o das fibras mioc&#225;rdicas e prolifera&#231;&#227;o de fibroblastos, com forma&#231;&#227;o de pequenas placas fibr&#243;ticas distribu&#237;das pelo mioc&#225;rdio. Para compensar a defici&#234;ncia funcional das fibras mioc&#225;rdicas e para manter a din&#226;mica circulat&#243;ria, ocorre dilata&#231;&#227;o dos ventr&#237;culos<sup>11</sup>. Assim, o tamanho do cora&#231;&#227;o na miocardiopatia chag&#225;sica cr&#244;nica guarda uma rela&#231;&#227;o estreita com o grau de les&#227;o mioc&#225;rdica, predispondo maior incid&#234;ncia de ECV de origem arr&#237;tmica<sup>12-14</sup> e tromboemb&#243;lica<sup>4,15,16</sup>.</p>
    <p>Recentemente, a microscopia confocal tridimensional p&#244;de evidenciar importante e difusa dilata&#231;&#227;o e tortuosidade das arter&#237;olas, causando uma perfus&#227;o tecidual inadequada com m&#250;ltiplos infartos. As &#225;reas de fibrose resultantes podem tamb&#233;m causar obstru&#231;&#227;o no trajeto dos vasos provocando les&#245;es isqu&#234;micas<sup>17</sup>. Outro estudo correlacionou a disfun&#231;&#227;o mioc&#225;rdica diretamente com a quantidade de col&#225;geno no interst&#237;cio do mioc&#225;rdio<sup>18</sup>. </p>
    <p>O EEF &#233; um m&#233;todo importante para detalhar as poss&#237;veis altera&#231;&#245;es no sistema &#233;xcito-condutor presentes na doen&#231;a de Chagas. Assim, o significado do intervalo AH foi estudado em pacientes n&#227;o-chag&#225;sicos com BCRD associado a BDAS, observando-se uma maior incid&#234;ncia de doen&#231;a card&#237;aca org&#226;nica e disfun&#231;&#227;o mioc&#225;rdica quando apresentavam um aumento desse intervalo<sup>19</sup>. Apesar disso, em seguimento de tr&#234;s anos n&#227;o houve diferen&#231;a estat&#237;stica em rela&#231;&#227;o ao n&#250;mero de MS e mortalidade geral, ao serem comparados pacientes com intervalo AH normal e aumentado. No presente trabalho, o aumento do intervalo AH ocorreu em 17,8% dos pacientes, incid&#234;ncia proporcionalmente similar &#224;s observadas em n&#227;o-chag&#225;sicos<sup>19-21</sup>, n&#227;o sendo apreciada uma rela&#231;&#227;o estatisticamente significante entre ECV e valores do intervalo AH. Em tr&#234;s pacientes foi observada normaliza&#231;&#227;o do intervalo AH no 2&#186; EEF, provavelmente em raz&#227;o da flutua&#231;&#227;o vagal. </p>
    <p>O aumento do PW ocorreu em maior n&#250;mero de indiv&#237;duos, confirmando essa freq&#252;ente altera&#231;&#227;o na doen&#231;a de Chagas, parecendo ser mais sens&#237;vel na identifica&#231;&#227;o do dist&#250;rbio da condu&#231;&#227;o nodal, visto mostrar-se alterado em v&#225;rios pacientes com intervalo AH normal. Apenas quatro indiv&#237;duos apresentaram ECV, n&#227;o havendo uma rela&#231;&#227;o estatisticamente significante com o aumento do PW. </p>
    <p>O dist&#250;rbio da condu&#231;&#227;o no sistema His-Purkinje &#233; freq&#252;ente em chag&#225;sicos, sendo geralmente a causa do bloqueio AV total. V&#225;rios estudos em pacientes n&#227;o-chag&#225;sicos relacionaram aumento do intervalo HV com eventos card&#237;acos<sup>19,22,23</sup>. Um deles avaliando 517 indiv&#237;duos n&#227;o-chag&#225;sicos com bloqueio bifascicular e com seguimento m&#233;dio de 3,4 anos observou uma rela&#231;&#227;o entre intervalo HV prolongado e maior incid&#234;ncia e gravidade de doen&#231;a card&#237;aca org&#226;nica, notando-se com maior freq&#252;&#234;ncia insufici&#234;ncia card&#237;aca com classe funcional mais avan&#231;ada, angina do peito e infarto do mioc&#225;rdio pr&#233;vio<sup>22</sup>. Al&#233;m disso, mortalidade geral e MS foram significativamente mais freq&#252;entes no grupo em que se evidenciava aumento do intervalo HV. Dois outros estudos com tr&#234;s anos e oito meses, respectivamente, confirmaram a maior incid&#234;ncia de bloqueio AV e mortalidade em indiv&#237;duos n&#227;o-chag&#225;sicos com essas altera&#231;&#245;es<sup>19,23</sup>. Outras observa&#231;&#245;es<sup>24,25</sup>, no entanto, n&#227;o reproduziram esses resultados. Neste trabalho, em chag&#225;sicos, a correla&#231;&#227;o entre ECV e intervalo HV aumentado s&#243; mostrou signific&#226;ncia estat&#237;stica quando o c&#225;lculo foi realizado com valores desse intervalo iguais ou superiores a 70 ms. </p>
    <p>O tempo de recupera&#231;&#227;o do n&#243;dulo sinusal pode ser influenciado por idade, doen&#231;a associada, metodologia empregada e principalmente pelo comprimento do ciclo de repouso, raz&#227;o pela qual foi utilizado o TCRS. A compara&#231;&#227;o entre pacientes n&#227;o-chag&#225;sicos portadores de bloqueio bi ou trifascicular com outros que apresentavam complexos QRS normais mostrou porcentagem claramente superior de anormalidades eletrofisiol&#243;gicas no n&#243;dulo sinusal e no &#225;trio no primeiro grupo<sup>26</sup>. Em indiv&#237;duos chag&#225;sicos, a fun&#231;&#227;o do n&#243;dulo sinusal foi avaliada em v&#225;rios estudos, havendo altera&#231;&#227;o no TCRS em porcentagens vari&#225;veis, dependendo da sintomatologia, da forma da doen&#231;a (indeterminada ou n&#227;o), da sua avalia&#231;&#227;o com ou sem bloqueio auton&#244;mico ou por meio do uso de atropina isoladamente<sup>5,10,27-32</sup>. O mecanismo da disfun&#231;&#227;o sinusal freq&#252;entemente &#233; misto, havendo comprometimento do automatismo e da condu&#231;&#227;o sinoatrial. Em indiv&#237;duos com a forma cr&#244;nica da doen&#231;a de Chagas, com e sem insufici&#234;ncia card&#237;aca, o TCRS &#233; anormal em porcentagem significativa, variando de 18,1% a 45%<sup>10,31,32</sup>, observando-se os menores valores em assintom&#225;ticos. O estudo de pacientes chag&#225;sicos cr&#244;nicos assintom&#225;ticos com BCRD e n&#227;o-chag&#225;sicos com BCRD ou bloqueio completo de ramo esquerdo mostrou que o TCRS alterado foi importante indicador de disfun&#231;&#227;o sintom&#225;tica do n&#243;dulo sinusal, havendo, por&#233;m, uma correla&#231;&#227;o com mortalidade de causa card&#237;aca apenas em indiv&#237;duos n&#227;o-chag&#225;sicos<sup>33</sup>. No presente estudo, a incid&#234;ncia de altera&#231;&#227;o no TCRS foi proporcionalmente similar aos menores resultados da literatura, possivelmente pelo grande n&#250;mero de pacientes assintom&#225;ticos presentes na amostra. A rela&#231;&#227;o desse par&#226;metro alterado com ECV n&#227;o mostrou signific&#226;ncia estat&#237;stica.</p>
    <p>A incid&#234;ncia de ECV observada ao final do estudo foi de 31,1%. A fisiopatologia da MS permanece incerta, mas sabe-se que a miocardite fibrosante cr&#244;nica iniciada e perpetrada por altera&#231;&#245;es na microcircula&#231;&#227;o mioc&#225;rdica, fatores auto-imunes, conjuntamente com les&#227;o no sistema nervoso aut&#244;nomo<sup>34</sup> e disfun&#231;&#227;o ventricular esquerda aumentam claramente o seu risco. Uma revis&#227;o realizada recentemente reafirma os preditores de MS, apontando a variabilidade da freq&#252;&#234;ncia card&#237;aca e a an&#225;lise da dispers&#227;o do intervalo QT como novos m&#233;todos para estratifica&#231;&#227;o de risco<sup>35</sup>. Dos pacientes com MS, nenhum apresentava insufici&#234;ncia card&#237;aca descompensada, refor&#231;ando a hip&#243;tese de arritmia card&#237;aca como causa do evento. </p>
    <p>Tromboembolismo pulmonar e sist&#234;mico &#233; freq&#252;ente na doen&#231;a de Chagas<sup>4,15</sup>. No primeiro, em geral nota-se a presen&#231;a de trombose intracavit&#225;ria e n&#227;o trombose venosa perif&#233;rica como origem do foco embolig&#234;nico. O acometimento sist&#234;mico costuma ser mais ami&#250;de nos rins e ba&#231;o, sendo mais raro no c&#233;rebro<sup>4,15</sup>, tornando-se comum nos casos em que h&#225; les&#227;o apical<sup>36</sup>. No presente estudo, dos cinco casos de tromboembolismo, quatro deslocaram-se para o c&#233;rebro e apenas um para o pulm&#227;o. Tal fato pode dever-se ao pequeno n&#250;mero de pacientes com insufici&#234;ncia card&#237;aca descompensada, que seria o fator predisponente para embolia pulmonar. </p>
    <p>A TVS na doen&#231;a de Chagas &#233; indicativo de gravidade, observando-se mortalidade de quase 100% em cinco anos<sup>37</sup>. Sua indu&#231;&#227;o por meio de estimula&#231;&#227;o ventricular programada &#233; um importante preditor de morte card&#237;aca de origem arr&#237;tmica e mortalidade geral em pacientes com taquicardia ventricular n&#227;o-sustentada<sup>38</sup>. Pacientes que apresentam TVS com repercuss&#227;o hemodin&#226;mica mostram prognose nitidamente pior que os assintom&#225;ticos ou aqueles que n&#227;o apresentaram TVS<sup>39</sup>. Predomina na regi&#227;o basal seguida da regi&#227;o septal e apical<sup>40</sup>, sendo a reentrada o mecanismo da arritmia<sup>41</sup>. No grupo estudado, s&#243; um paciente apresentou TVS ao Holter de 24 horas e ao EEF, possivelmente pelo grande n&#250;mero de pacientes assintom&#225;ticos, e tamb&#233;m pelo fato de os protocolos de estimula&#231;&#227;o ventricular na &#233;poca do in&#237;cio do estudo serem menos agressivos, em raz&#227;o de problemas &#233;ticos. </p>
    <p>A MCT pode ser causada por insufici&#234;ncia card&#237;aca congestiva (ICC), por&#233;m n&#227;o raramente o curso da doen&#231;a &#233; abreviado por taquiarritmia ventricular maligna ou epis&#243;dio de embolia pulmonar. Este estudo mostrou que os tr&#234;s pacientes que faleceram em ICC j&#225; tinham apresentado previamente um ECV, embolia pulmonar, TVS ou AVCI. </p>
    <p>Assim, as altera&#231;&#245;es evolutivas do sistema &#233;xcito-condutor do cora&#231;&#227;o mostraram-se lentas, progressivas e difusas, permitindo identificar a import&#226;ncia e a freq&#252;&#234;ncia do comprometimento de cada um de seus segmentos, revelando quais deles apresentavam rela&#231;&#227;o com os ECV. Essas informa&#231;&#245;es s&#227;o de grande valia para os pacientes, reservando para aqueles com pior prognose um acompanhamento mais rigoroso com exames cl&#237;nico e laboratorial mais freq&#252;entes.</p>
    <p>
      <fn id="end" fn-type="corresp">
        <label>
          <bold>Correspond&#234;ncia</bold>
        </label>
        <p> Ney Valente </p>
        <p> Rua 1&#186; de Mar&#231;o, 193 </p>
        <p> 04044-040 &#150; S&#227;o Paulo, SP </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="pimenta@cardiol.br">pimenta@cardiol.br</email>
        </p>
      </fn>
    </p>
    <p> Recebido em 01/02/04 </p>
    <p> Aceito em 18/05/05</p>
  </body>
  <back>
    <ref-list>
      <ref id="B1">
        <mixed-citation>1. Bestetti RB, Dalbo CM, Arruda CA, Correia    Filho D, Freitas OC. Predictors of sudden cardiac death for patients with Chagas    disease: a hospital-derived cohort study. Cardiology 1996; 87: 481-7.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Predictors of sudden cardiac death for patients with Chagas&#8217; disease: a hospital-derived cohort study</article-title>
          <source>Cardiology</source>
          <date>
            <year>1996</year>
          </date>
          <fpage>481</fpage>
          <lpage>7</lpage>
          <volume>87</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Bestetti</surname>
              <given-names>RB</given-names>
            </name>
            <name>
              <surname>Dalbo</surname>
              <given-names>CM</given-names>
            </name>
            <name>
              <surname>Arruda</surname>
              <given-names>CA</given-names>
            </name>
            <name>
              <surname>Correia</surname>
              <given-names>Filho D</given-names>
            </name>
            <name>
              <surname>Freitas</surname>
              <given-names>OC</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B2">
        <mixed-citation>2. De Paola AAV. Estimula&#231;&#227;o    ventricular programada em pacientes com cardiopatia chag&#225;sica cr&#244;nica    e taquicardia ventricular. S&#227;o Paulo, 1990. Tese (Livre-Doc&#234;ncia)     Escola Paulista de Medicina.</mixed-citation>
        <element-citation publication-type="book">
          <source>Estimula&#231;&#227;o ventricular programada em pacientes com cardiopatia chag&#225;sica cr&#244;nica e taquicardia ventricular</source>
          <date>
            <year>1990</year>
          </date>
          <person-group person-group-type="author">
            <name>
              <surname>De Paola</surname>
              <given-names>AAV.</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B3">
        <mixed-citation>3. Espinosa RA, Carrasco HA, Belandria F,    Fuenmayor AM, Molina C, Gonz&#225;lez R et al. Life expectancy analysis in    patients with Chagas disease: Prognosis after one decade (1973-1983). Int J    Cardiol 1985; 8: 45-56.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Life expectancy analysis in patients with Chagas&#8217; disease: Prognosis after one decade (1973-1983)</article-title>
          <source>Int J Cardiol</source>
          <date>
            <year>1985</year>
          </date>
          <fpage>45</fpage>
          <lpage>56</lpage>
          <volume>8</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Espinosa</surname>
              <given-names>RA</given-names>
            </name>
            <name>
              <surname>Carrasco</surname>
              <given-names>HA</given-names>
            </name>
            <name>
              <surname>Belandria</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Fuenmayor</surname>
              <given-names>AM</given-names>
            </name>
            <name>
              <surname>Molina</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Gonz&#225;lez</surname>
              <given-names>R</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B4">
        <mixed-citation>4. Arteaga-Fernandez E, Barreto ACP, Ianni    BM, Mady C, Lopez EA, Vianna CB et al. Trombose card&#237;aca e embolia em    pacientes falecidos de cardiopatia chag&#225;sica cr&#244;nica. Arq Bras    Cardiol 1989; 52: 189-92.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Trombose card&#237;aca e embolia em pacientes falecidos de cardiopatia chag&#225;sica cr&#244;nica</article-title>
          <source>Arq Bras Cardiol</source>
          <date>
            <year>1989</year>
          </date>
          <fpage>189</fpage>
          <lpage>92</lpage>
          <volume>52</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Arteaga-Fernandez</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Barreto</surname>
              <given-names>ACP</given-names>
            </name>
            <name>
              <surname>Ianni</surname>
              <given-names>BM</given-names>
            </name>
            <name>
              <surname>Mady</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Lopez</surname>
              <given-names>EA</given-names>
            </name>
            <name>
              <surname>Vianna</surname>
              <given-names>CB</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B5">
        <mixed-citation>5. Benchimol CB, Ginefra P, Benchimol AB.    Avalia&#231;&#227;o eletrofisiol&#243;gica. In: Can&#231;ado JR, Chuster    M.: Cardiopatia chag&#225;sica. Belo Horizonte: Funda&#231;&#227;o Carlos    Chagas de Pesquisas M&#233;dicas, 1985, 213-22.</mixed-citation>
        <element-citation publication-type="book">
          <source>Cardiopatia chag&#225;sica</source>
          <date>
            <year>1985</year>
          </date>
          <fpage>213</fpage>
          <lpage>22</lpage>
          <person-group person-group-type="author">
            <name>
              <surname>Benchimol</surname>
              <given-names>CB</given-names>
            </name>
            <name>
              <surname>Ginefra</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Benchimol</surname>
              <given-names>AB</given-names>
            </name>
            <name>
              <surname>Can&#231;ado</surname>
              <given-names>JR</given-names>
            </name>
            <name>
              <surname>Chuster</surname>
              <given-names>M.</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B6">
        <mixed-citation>6. Carrasco HA, Gerrero L, Parada H, Molia    C, Vegas E, Chuecos R. Ventricular arrhythmias and left ventricular myocardial    function in chronic chagasic patients. Int J Cardiol 1990; 28: 35-41.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Ventricular arrhythmias and left ventricular myocardial function in chronic chagasic patients</article-title>
          <source>Int J Cardiol</source>
          <date>
            <year>1990</year>
          </date>
          <fpage>35</fpage>
          <lpage>41</lpage>
          <volume>28</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Carrasco</surname>
              <given-names>HA</given-names>
            </name>
            <name>
              <surname>Gerrero</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Parada</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Molia</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Vegas</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Chuecos</surname>
              <given-names>R</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B7">
        <mixed-citation>7. Peters RW, Scheinman MM, Dhingra R, Rosen    K, McAnulty J, Rahimtoola SH et al. Serial electrophysiological studies in patients    with chronic bundle branch block. Circulation 1982; 65: 1480-5.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Serial electrophysiological studies in patients with chronic bundle branch block</article-title>
          <source>Circulation</source>
          <date>
            <year>1982</year>
          </date>
          <fpage>1480</fpage>
          <lpage>5</lpage>
          <volume>65</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Peters</surname>
              <given-names>RW</given-names>
            </name>
            <name>
              <surname>Scheinman</surname>
              <given-names>MM</given-names>
            </name>
            <name>
              <surname>Dhingra</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Rosen</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>McAnulty</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Rahimtoola</surname>
              <given-names>SH</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B8">
        <mixed-citation>8. Prystowsky EN, Pritchett ELC, Roses AD,    Gallagher J. The natural history of conduction system disease in myotonic muscular    dystrophy, as determined by serial electrophysiological studies. Circulation    1979; 60: 1360-4.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>The natural history of conduction system disease in myotonic muscular dystrophy, as determined by serial electrophysiological studies</article-title>
          <source>Circulation</source>
          <date>
            <year>1979</year>
          </date>
          <fpage>1360</fpage>
          <lpage>4</lpage>
          <volume>60</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Prystowsky</surname>
              <given-names>EN</given-names>
            </name>
            <name>
              <surname>Pritchett</surname>
              <given-names>ELC</given-names>
            </name>
            <name>
              <surname>Roses</surname>
              <given-names>AD</given-names>
            </name>
            <name>
              <surname>Gallagher</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B9">
        <mixed-citation>9. Scherlag BJ, Lau SH, Helfant RH, Berkowitz    WD, Stein E, Damato NA. Catheter technique for recording His bundle activity    in man. Circulation 1969; 39: 13-8.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Catheter technique for recording His bundle activity in man</article-title>
          <source>Circulation</source>
          <date>
            <year>1969</year>
          </date>
          <fpage>13</fpage>
          <lpage>8</lpage>
          <volume>39</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Scherlag</surname>
              <given-names>BJ</given-names>
            </name>
            <name>
              <surname>Lau</surname>
              <given-names>SH</given-names>
            </name>
            <name>
              <surname>Helfant</surname>
              <given-names>RH</given-names>
            </name>
            <name>
              <surname>Berkowitz</surname>
              <given-names>WD</given-names>
            </name>
            <name>
              <surname>Stein</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Damato</surname>
              <given-names>NA</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B10">
        <mixed-citation>10. Pimenta J, Miranda M, Pereira CB. Electrophysiological    findings in long-term asymptomatic chagasic individuals. Am Heart J 1983; 106:    374-80.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Electrophysiological findings in long-term asymptomatic chagasic individuals</article-title>
          <source>Am Heart J</source>
          <date>
            <year>1983</year>
          </date>
          <fpage>374</fpage>
          <lpage>80</lpage>
          <volume>106</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Pimenta</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Miranda</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Pereira</surname>
              <given-names>CB</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B11">
        <mixed-citation>11. Anselmi A, Pifano F, Suarez JA, Gurdiel    O, Lapco L. Cardiovascular radiology in acute and chronic Chagas myocardiopathy.    Morphologic and dynamic study of the cardiac contour, correlated with the histological    changes observed in myocardiopathies attributed to Schizotrypanum cruzi. Am    Heart J 1967; 73: 626-39.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Morphologic and dynamic study of the cardiac contour, correlated with the histological changes observed in myocardiopathies attributed to Schizotrypanum cruzi</article-title>
          <source>Am Heart J</source>
          <date>
            <year>1967</year>
          </date>
          <fpage>626</fpage>
          <lpage>39</lpage>
          <volume>73</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Anselmi</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Pifano</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Suarez</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Gurdiel</surname>
              <given-names>O</given-names>
            </name>
            <name>
              <surname>Lapco</surname>
              <given-names>L.</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B12">
        <mixed-citation>12. Carrasco HA, Parada H, Gerrero L, Duque    M, Duran D, Molina C. Prognostic implications of clinical, electrocardiographic,    and hemodynamic findings in chronic Chagas disease. Int J Cardiol 1994; 43:    27-38.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Prognostic implications of clinical, electrocardiographic, and hemodynamic findings in chronic Chagas&#8217; disease</article-title>
          <source>Int J Cardiol</source>
          <date>
            <year>1994</year>
          </date>
          <fpage>27</fpage>
          <lpage>38</lpage>
          <volume>43</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Carrasco</surname>
              <given-names>HA</given-names>
            </name>
            <name>
              <surname>Parada</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Gerrero</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Duque</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Duran</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Molina</surname>
              <given-names>C</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B13">
        <mixed-citation>13. Bestetti RB, Muccillo G. Clinical course    of Chagas heart disease: A comparison with dilated cardiomyopathy. Int J Cardiol    1997; 60: 187-93.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Clinical course of Chagas&#8217; heart disease: A comparison with dilated cardiomyopathy</article-title>
          <source>Int J Cardiol</source>
          <date>
            <year>1997</year>
          </date>
          <fpage>187</fpage>
          <lpage>93</lpage>
          <volume>60</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Bestetti</surname>
              <given-names>RB</given-names>
            </name>
            <name>
              <surname>Muccillo</surname>
              <given-names>G</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B14">
        <mixed-citation>14. Barreto ACP, Bellotti G, Deperon SD, Arteaga-Fernandez    E, Mady C, Ianni BM et al. O valor do eletrocardiograma na avalia&#231;&#227;o    da fun&#231;&#227;o mioc&#225;rdica dos portadores de doen&#231;a de    Chagas. Arq Bras Cardiol 1989; 52: 69-73.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>O valor do eletrocardiograma na avalia&#231;&#227;o da fun&#231;&#227;o mioc&#225;rdica dos portadores de doen&#231;a de Chagas</article-title>
          <source>Arq Bras Cardiol</source>
          <date>
            <year>1989</year>
          </date>
          <fpage>69</fpage>
          <lpage>73</lpage>
          <volume>52</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Barreto</surname>
              <given-names>ACP</given-names>
            </name>
            <name>
              <surname>Bellotti</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Deperon</surname>
              <given-names>SD</given-names>
            </name>
            <name>
              <surname>Arteaga-Fernandez</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Mady</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Ianni</surname>
              <given-names>BM</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B15">
        <mixed-citation>15. Oliveira JSM, Araujo RRC, Navarro MA,    Muccillo G. Cardiac thrombosis and thromboembolism in chronic Chagas heart    disease. Am J Cardiol 1983; 52: 147-51.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Cardiac thrombosis and thromboembolism in chronic Chagas&#8217; heart disease</article-title>
          <source>Am J Cardiol</source>
          <date>
            <year>1983</year>
          </date>
          <fpage>147</fpage>
          <lpage>51</lpage>
          <volume>52</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Oliveira</surname>
              <given-names>JSM</given-names>
            </name>
            <name>
              <surname>Araujo</surname>
              <given-names>RRC</given-names>
            </name>
            <name>
              <surname>Navarro</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Muccillo</surname>
              <given-names>G</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B16">
        <mixed-citation>16. Elian AA. Aspectos cl&#237;nicos do    tromboembolismo. In Can&#231;ado SR, Chuster M. Cardiopatia chag&#225;sica    . Belo Horizonte: Funda&#231;&#227;o Carlos Chagas, 1985, 314-22.</mixed-citation>
        <element-citation publication-type="book">
          <source>Cardiopatia chag&#225;sica</source>
          <date>
            <year>1985</year>
          </date>
          <fpage>314</fpage>
          <lpage>22</lpage>
          <person-group person-group-type="author">
            <name>
              <surname>Elian</surname>
              <given-names>AA.</given-names>
            </name>
            <name>
              <surname>Can&#231;ado</surname>
              <given-names>SR</given-names>
            </name>
            <name>
              <surname>Chuster</surname>
              <given-names>M.</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B17">
        <mixed-citation>17. Higuchi ML, Fukasawa S, De Brito T, Parzianello    LC, Bellotti G, Ramires JAF. Different microcirculatory and interstitial matrix    patterns in idiopathic dilated cardiomyopathy and Chagas disease: a three dimensional    confocal microscopy study. Heart 1999; 82: 279-85.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Different microcirculatory and interstitial matrix patterns in idiopathic dilated cardiomyopathy and Chagas&#8217; disease: a three dimensional confocal microscopy study</article-title>
          <source>Heart</source>
          <date>
            <year>1999</year>
          </date>
          <fpage>279</fpage>
          <lpage>85</lpage>
          <volume>82</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Higuchi</surname>
              <given-names>ML</given-names>
            </name>
            <name>
              <surname>Fukasawa</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>De Brito</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Parzianello</surname>
              <given-names>LC</given-names>
            </name>
            <name>
              <surname>Bellotti</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Ramires</surname>
              <given-names>JAF</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B18">
        <mixed-citation>18. Mady C, Ianni BM, Arteaga E, Montes GS,    Caldini EG, Andrade G et al. Relation between interstitial myocardial collagen    and the degree of clinical impairment in Chagas disease. Am J Cardiol 1999;    84: 354-6.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Relation between interstitial myocardial collagen and the degree of clinical impairment in Chagas&#8217; disease</article-title>
          <source>Am J Cardiol</source>
          <date>
            <year>1999</year>
          </date>
          <fpage>354</fpage>
          <lpage>6</lpage>
          <volume>84</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Mady</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Ianni</surname>
              <given-names>BM</given-names>
            </name>
            <name>
              <surname>Arteaga</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Montes</surname>
              <given-names>GS</given-names>
            </name>
            <name>
              <surname>Caldini</surname>
              <given-names>EG</given-names>
            </name>
            <name>
              <surname>Andrade</surname>
              <given-names>G</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B19">
        <mixed-citation>19. Dhingra RC, Wyndham C, Amat-Y-Leon F,    Wu D, Denes P, Towne WD et al. Significance of A-H interval in patients with    chronic bundle branch block. Clinical, electrophysiological and follow-up observations.    Am J Cardiol 1976; 37: 231-6.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Significance of A-H interval in patients with chronic bundle branch block</article-title>
          <source>Clinical, electrophysiological and follow-up observations. Am J Cardiol</source>
          <date>
            <year>1976</year>
          </date>
          <fpage>231</fpage>
          <lpage>6</lpage>
          <volume>37</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Dhingra</surname>
              <given-names>RC</given-names>
            </name>
            <name>
              <surname>Wyndham</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Amat-Y-Leon</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Wu</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Denes</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Towne</surname>
              <given-names>WD</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B20">
        <mixed-citation>20. Narula OS, Samet P. Right bundle branch    block with normal left or right axis deviation. Analysis by His bundle recordings.    Am J Med 1971; 51: 432-55. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Analysis by His bundle recordings</article-title>
          <source>Am J Med</source>
          <date>
            <year>1971</year>
          </date>
          <fpage>432</fpage>
          <lpage>55</lpage>
          <volume>51</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Narula</surname>
              <given-names>OS</given-names>
            </name>
            <name>
              <surname>Samet</surname>
              <given-names>P.</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B21">
        <mixed-citation>21. Levites R, Haft JL. Significance of first    degree heart block (prolonged P-R interval) in bifascicular block. Am J Cardiol    1974; 34: 259-64.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Significance of first degree heart block (prolonged P-R interval) in bifascicular block</article-title>
          <source>Am J Cardiol</source>
          <date>
            <year>1974</year>
          </date>
          <fpage>259</fpage>
          <lpage>64</lpage>
          <volume>34</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Levites</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Haft</surname>
              <given-names>JL</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B22">
        <mixed-citation>22. Dhingra RC, Lalileo E, Strasberg B, Swiryn    S, Bauernfeind RA, Wyndham CRC et al. Significance of the HV interval in 517    patients with chronic bifascicular block. Circulation 1981; 64:1265-71.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Significance of the HV interval in 517 patients with chronic bifascicular block</article-title>
          <source>Circulation</source>
          <date>
            <year>1981</year>
          </date>
          <fpage>1265</fpage>
          <lpage>71</lpage>
          <volume>64</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Dhingra</surname>
              <given-names>RC</given-names>
            </name>
            <name>
              <surname>Lalileo</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Strasberg</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Swiryn</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Bauernfeind</surname>
              <given-names>RA</given-names>
            </name>
            <name>
              <surname>Wyndham</surname>
              <given-names>CRC</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B23">
        <mixed-citation>23. Scheinman M, Weiss A, Kunfel F. His bundle    recording in patients with bundle branch block and transient neurologic symptoms.    Circulation 1973; 48: 322-30.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>His bundle recording in patients with bundle branch block and transient neurologic symptoms</article-title>
          <source>Circulation</source>
          <date>
            <year>1973</year>
          </date>
          <fpage>322</fpage>
          <lpage>30</lpage>
          <volume>48</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Scheinman</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Weiss</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Kunfel</surname>
              <given-names>F</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B24">
        <mixed-citation>24. Denes P, Dhingra RC, Wu D, Chuquimia R,    Amat-Y-Leon F, Wyndham C et al. H-V interval in patients with bifascicular block    (right bundle branch block and left anterior hemiblock). Am J Cardiol 1975;    35: 23-9.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>H-V interval in patients with bifascicular block (right bundle branch block and left anterior hemiblock)</article-title>
          <source>Am J Cardiol</source>
          <date>
            <year>1975</year>
          </date>
          <fpage>23</fpage>
          <lpage>9</lpage>
          <volume>35</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Denes</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Dhingra</surname>
              <given-names>RC</given-names>
            </name>
            <name>
              <surname>Wu</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Chuquimia</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Amat-Y-Leon</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Wyndham</surname>
              <given-names>C</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B25">
        <mixed-citation>25. McAnulty JH, Rahimtoola SH, Murphy E,    Demots H, Ritzmann L, Kanarek PE et al. Natural history of "high-risk"    bundle branch block. Final report of a prospective study. N Engl J Med 1982;    307: 137-43. </mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Natural history of "high-risk" bundle branch block</article-title>
          <source>Final report of a prospective study. N Engl J Med</source>
          <date>
            <year>1982</year>
          </date>
          <fpage>137</fpage>
          <lpage>43</lpage>
          <volume>307</volume>
          <person-group person-group-type="author">
            <name>
              <surname>McAnulty</surname>
              <given-names>JH</given-names>
            </name>
            <name>
              <surname>Rahimtoola</surname>
              <given-names>SH</given-names>
            </name>
            <name>
              <surname>Murphy</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Demots</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Ritzmann</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Kanarek</surname>
              <given-names>PE</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B26">
        <mixed-citation>26. Wise DG, McAnulty JH, Rahimtoola SH, Murphy    ES. Electrophysiological abnormalities of the sinus node and atrium in patients    with bundle branch block. Circulation 1979; 60: 413-20.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Electrophysiological abnormalities of the sinus node and atrium in patients with bundle branch block</article-title>
          <source>Circulation</source>
          <date>
            <year>1979</year>
          </date>
          <fpage>413</fpage>
          <lpage>20</lpage>
          <volume>60</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Wise</surname>
              <given-names>DG</given-names>
            </name>
            <name>
              <surname>McAnulty</surname>
              <given-names>JH</given-names>
            </name>
            <name>
              <surname>Rahimtoola</surname>
              <given-names>SH</given-names>
            </name>
            <name>
              <surname>Murphy</surname>
              <given-names>ES</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B27">
        <mixed-citation>27. Sosa EA. Contribui&#231;&#227;o ao    estudo da condu&#231;&#227;o &#225;trio-ventricular na forma cr&#244;nica    indeterminada da doen&#231;a de Chagas. S&#227;o Paulo, 1977. Disserta&#231;&#227;o    (Mestrado) - Faculdade de Medicina, Universidade de S&#227;o Paulo.</mixed-citation>
        <element-citation publication-type="book">
          <source>Contribui&#231;&#227;o ao estudo da condu&#231;&#227;o &#225;trio-ventricular na forma cr&#244;nica indeterminada da doen&#231;a de Chagas</source>
          <date>
            <year>1977</year>
          </date>
          <person-group person-group-type="author">
            <name>
              <surname>Sosa</surname>
              <given-names>EA.</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B28">
        <mixed-citation>28. Sosa EA. Contribui&#231;&#227;o para    o estudo das propriedades eletrofisiol&#243;gicas do cora&#231;&#227;o    na doen&#231;a de Chagas. S&#227;o Paulo, 1979. Tese (Doutorado) - Faculdade    de Medicina, Universidade de S&#227;o Paulo.</mixed-citation>
        <element-citation publication-type="book">
          <source>Contribui&#231;&#227;o para o estudo das propriedades eletrofisiol&#243;gicas do cora&#231;&#227;o na doen&#231;a de Chagas</source>
          <date>
            <year>1979</year>
          </date>
          <person-group person-group-type="author">
            <name>
              <surname>Sosa</surname>
              <given-names>EA.</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B29">
        <mixed-citation>29. Benchimol CB, Kreuzig R, Ginefra P, Schlesinger    P, Benchimol AB. A disfun&#231;&#227;o do n&#243;dulo sinusal na cardiopatia    chag&#225;sica cr&#244;nica. Arq Bras Cardiol 1977; 30: 337-44.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>A disfun&#231;&#227;o do n&#243;dulo sinusal na cardiopatia chag&#225;sica cr&#244;nica</article-title>
          <source>Arq Bras Cardiol</source>
          <date>
            <year>1977</year>
          </date>
          <fpage>337</fpage>
          <lpage>44</lpage>
          <volume>30</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Benchimol</surname>
              <given-names>CB</given-names>
            </name>
            <name>
              <surname>Kreuzig</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Ginefra</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Schlesinger</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Benchimol</surname>
              <given-names>AB</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B30">
        <mixed-citation>30. Benchimol CB. Disfun&#231;&#227;o    do n&#243;dulo sinusal na doen&#231;a de Chagas. Contribui&#231;&#227;o    cl&#237;nica, eletrofisiol&#243;gica e farmacol&#243;gica. Correla&#231;&#227;o    com a hemodin&#226;mica e cineangiocardiografia do ventr&#237;culo esquerdo.    Rio de Janeiro 1981. Tese (Doutorado) -- Universidade Federal do Rio de Janeiro.</mixed-citation>
        <element-citation publication-type="book">
          <source>Disfun&#231;&#227;o do n&#243;dulo sinusal na doen&#231;a de Chagas. Contribui&#231;&#227;o cl&#237;nica, eletrofisiol&#243;gica e farmacol&#243;gica: Correla&#231;&#227;o com a hemodin&#226;mica e cineangiocardiografia do ventr&#237;culo esquerdo.</source>
          <date>
            <year>1981</year>
          </date>
          <person-group person-group-type="author">
            <name>
              <surname>Benchimol</surname>
              <given-names>CB</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B31">
        <mixed-citation>31. Maia IG, S&#225; RS, Loyola LHC, Ara&#250;jo    PP, Monteiro SM, Amino JGC et al. O n&#243;dulo sinusal na cardiopatia chag&#225;sica    cr&#244;nica. Arq Bras Cardiol 1983; 40: 91-6.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>O n&#243;dulo sinusal na cardiopatia chag&#225;sica cr&#244;nica</article-title>
          <source>Arq Bras Cardiol</source>
          <date>
            <year>1983</year>
          </date>
          <fpage>91</fpage>
          <lpage>6</lpage>
          <volume>40</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Maia</surname>
              <given-names>IG</given-names>
            </name>
            <name>
              <surname>S&#225;</surname>
              <given-names>RS</given-names>
            </name>
            <name>
              <surname>Loyola</surname>
              <given-names>LHC</given-names>
            </name>
            <name>
              <surname>Ara&#250;jo</surname>
              <given-names>PP</given-names>
            </name>
            <name>
              <surname>Monteiro</surname>
              <given-names>SM</given-names>
            </name>
            <name>
              <surname>Amino</surname>
              <given-names>JGC</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B32">
        <mixed-citation>32. Carrasco HA, Mora R, Inglessis G, Contreras    JM, Marval J, Fuenmayor A. Estudio de la funci&#243;n del nodo sinusal y de    la conducci&#243;n atrioventricular en pacientes con enfermedad de Chagas.    Arch Inst Cardiol Mex 1982; 52: 245-51.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Estudio de la funci&#243;n del nodo sinusal y de la conducci&#243;n atrioventricular en pacientes con enfermedad de Chagas</article-title>
          <source>Arch Inst Cardiol Mex</source>
          <date>
            <year>1982</year>
          </date>
          <fpage>245</fpage>
          <lpage>51</lpage>
          <volume>52</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Carrasco</surname>
              <given-names>HA</given-names>
            </name>
            <name>
              <surname>Mora</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Inglessis</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Contreras</surname>
              <given-names>JM</given-names>
            </name>
            <name>
              <surname>Marval</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Fuenmayor</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B33">
        <mixed-citation>33. Pimenta J, Valente N, Miranda M. Evolu&#231;&#227;o    cl&#237;nica a longo prazo, correlacionando a presen&#231;a de bloqueios    da condu&#231;&#227;o intraventricular em pacientes chag&#225;sicos e    n&#227;o chag&#225;sicos assintom&#225;ticos. Rev Soc Bras Med Trop 1999;    32: 621-31.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Evolu&#231;&#227;o cl&#237;nica a longo prazo, correlacionando a presen&#231;a de bloqueios da condu&#231;&#227;o intraventricular em pacientes chag&#225;sicos e n&#227;o chag&#225;sicos assintom&#225;ticos</article-title>
          <source>Rev Soc Bras Med Trop</source>
          <date>
            <year>1999</year>
          </date>
          <fpage>621</fpage>
          <lpage>31</lpage>
          <volume>32</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Pimenta</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Valente</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Miranda</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B34">
        <mixed-citation>34. Rossi MA, Bestetti RB. The challenge of    chagasic cardiomyopathy. The pathologic roles of autonomic abnormalities, autoimmune    mechanisms and microvascular changes and therapeutic implications. Cardiology    1995; 86: 1-7.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>The challenge of chagasic cardiomyopathy: The pathologic roles of autonomic abnormalities, autoimmune mechanisms and microvascular changes and therapeutic implications</article-title>
          <source>Cardiology</source>
          <date>
            <year>1995</year>
          </date>
          <fpage>1</fpage>
          <lpage>7</lpage>
          <volume>86</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Rossi</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Bestetti</surname>
              <given-names>RB.</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B35">
        <mixed-citation>35. Rassi Jr A, Rassi SG, Rassi A. Morte s&#250;bita    na doen&#231;a de Chagas. Arq Bras Cardiol 2001; 76: 75-85.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Morte s&#250;bita na doen&#231;a de Chagas</article-title>
          <source>Arq Bras Cardiol</source>
          <date>
            <year>2001</year>
          </date>
          <fpage>75</fpage>
          <lpage>85</lpage>
          <volume>76</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Rassi</surname>
              <given-names>Jr A</given-names>
            </name>
            <name>
              <surname>Rassi</surname>
              <given-names>SG</given-names>
            </name>
            <name>
              <surname>Rassi</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B36">
        <mixed-citation>36. Silva F, Marins N, Kagami SK, Silva CT,    Motta VP, Barbosa PH. Acidentes c&#233;rebro-vasculares tromboemb&#243;licos    e miocardiopatia chag&#225;sica. Arq Bras Cardiol 1979; 32: 45-9.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Acidentes c&#233;rebro-vasculares tromboemb&#243;licos e miocardiopatia chag&#225;sica</article-title>
          <source>Arq Bras Cardiol</source>
          <date>
            <year>1979</year>
          </date>
          <fpage>45</fpage>
          <lpage>9</lpage>
          <volume>32</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Silva</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Marins</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Kagami</surname>
              <given-names>SK</given-names>
            </name>
            <name>
              <surname>Silva</surname>
              <given-names>CT</given-names>
            </name>
            <name>
              <surname>Motta</surname>
              <given-names>VP</given-names>
            </name>
            <name>
              <surname>Barbosa</surname>
              <given-names>PH</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B37">
        <mixed-citation>37. Rassi A, Lorga AM, Rassi S. Abordagem    diagn&#243;stica e terap&#234;utica das arritmias na cardiopatia chag&#225;sica    cr&#244;nica. In Germiniani H. Diagn&#243;stico e terap&#234;utica das arritmias    card&#237;acas. 3&#350; ed. Rio de Janeiro: Editora Guanabara, 1990,    225-44.</mixed-citation>
        <element-citation publication-type="book">
          <source>Diagn&#243;stico e terap&#234;utica das arritmias card&#237;acas</source>
          <date>
            <year>1990</year>
          </date>
          <fpage>225</fpage>
          <lpage>44</lpage>
          <person-group person-group-type="author">
            <name>
              <surname>Rassi</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Lorga</surname>
              <given-names>AM</given-names>
            </name>
            <name>
              <surname>Rassi</surname>
              <given-names>S.</given-names>
            </name>
            <name>
              <surname>Germiniani</surname>
              <given-names>H.</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B38">
        <mixed-citation>38. Silva RMFL, Tavora MZP, Gondim FAA, Metha    N, Hara VM, Paola AAV. Valor preditivo das vari&#225;veis cl&#237;nicas    e eletrofisiol&#243;gicas em pacientes com miocardiopatia chag&#225;sica    cr&#244;nica e taquicardia ventricular n&#227;o-sustentada. Arq Bras Cardiol    2000; 75: 33-47.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Valor preditivo das vari&#225;veis cl&#237;nicas e eletrofisiol&#243;gicas em pacientes com miocardiopatia chag&#225;sica cr&#244;nica e taquicardia ventricular n&#227;o-sustentada</article-title>
          <source>Arq Bras Cardiol</source>
          <date>
            <year>2000</year>
          </date>
          <fpage>33</fpage>
          <lpage>47</lpage>
          <volume>75</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Silva</surname>
              <given-names>RMFL</given-names>
            </name>
            <name>
              <surname>Tavora</surname>
              <given-names>MZP</given-names>
            </name>
            <name>
              <surname>Gondim</surname>
              <given-names>FAA</given-names>
            </name>
            <name>
              <surname>Metha</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Hara</surname>
              <given-names>VM</given-names>
            </name>
            <name>
              <surname>Paola</surname>
              <given-names>AAV</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B39">
        <mixed-citation>39. Leite LR, Fenelon G, Sim&#245;es S.    Jr, Silva GG, Friedman PA, de Paola AA. Clinical usefulness of electrophysiological    testing in patients with ventricular tachycardia and chronic chagasic cardiomyopathy    treated with amiodarone or sotalol. J Cardiovasc Electrophysiol 2003; 14: 567-73.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Clinical usefulness of electrophysiological testing in patients with ventricular tachycardia and chronic chagasic cardiomyopathy treated with amiodarone or sotalol</article-title>
          <source>J Cardiovasc Electrophysiol</source>
          <date>
            <year>2003</year>
          </date>
          <fpage>567</fpage>
          <lpage>73</lpage>
          <volume>14</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Leite</surname>
              <given-names>LR</given-names>
            </name>
            <name>
              <surname>Fenelon</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Sim&#245;es</surname>
              <given-names>S. Jr</given-names>
            </name>
            <name>
              <surname>Silva</surname>
              <given-names>GG</given-names>
            </name>
            <name>
              <surname>Friedman</surname>
              <given-names>PA</given-names>
            </name>
            <name>
              <surname>de Paola</surname>
              <given-names>AA.</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B40">
        <mixed-citation>40. Takehara K, Scanavaca M, Sosa EA, Lopes    E, Marcial MB, Consolim FM et al. Aspectos anatomopatol&#243;gicos do foco    da taquicardia ventricular sustentada recorrente da miocardiopatia chag&#225;sica    cr&#244;nica. Arq Bras Cardiol 1990; 55: B-68. (Abstract)</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Aspectos anatomopatol&#243;gicos do foco da taquicardia ventricular sustentada recorrente da miocardiopatia chag&#225;sica cr&#244;nica</article-title>
          <source>Arq Bras Cardiol</source>
          <date>
            <year>1990</year>
          </date>
          <fpage>B</fpage>
          <lpage>68.</lpage>
          <volume>55</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Takehara</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Scanavaca</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Sosa</surname>
              <given-names>EA</given-names>
            </name>
            <name>
              <surname>Lopes</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Marcial</surname>
              <given-names>MB</given-names>
            </name>
            <name>
              <surname>Consolim</surname>
              <given-names>FM</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B41">
        <mixed-citation>41. Milei J, Pesce R, Valero E, Muratore C,    Beigelman R, Ferrans VJ. Electrophysiological-structural correlations in chagasic    aneurysm causing malignant arrhythmias. Int J Cardiol 1991; 32: 65-74.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Electrophysiological-structural correlations in chagasic aneurysm causing malignant arrhythmias</article-title>
          <source>Int J Cardiol</source>
          <date>
            <year>1991</year>
          </date>
          <fpage>65</fpage>
          <lpage>74</lpage>
          <volume>32</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Milei</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Pesce</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Valero</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Muratore</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Beigelman</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Ferrans</surname>
              <given-names>VJ</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
    </ref-list>
  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Serial electrophysiological studies of the heart&#8217;s excito conductor system in patients with chronic chagasic cardiopathy</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>OBJECTIVES: To study the evolution of lesions in conduction system using invasive electrophysiological studies (EPS), the impact of these alterations on cardiovascular events (CVE), and the frequency of these events in chronic chagasic patients. METHODS: Prospective study, initiated in 1979 with clinical follow-up until 2000, with the participation of 28 chronic chagasic patients that were 18 to 65 years old, with bundle branch and/or atrioventricular blocks. The patients were submitted to two EPS with a minimum interval of four years between the studies in order to assess five electrophysiologis parameters that were correlated with CVE. A 24-hour Holter and echocardiogram were performed. RESULTS: The average follow-up time after the first EPS was 154.5 months while the interval between EPS was 107.5 months. Ages ranged from 25 to 65 years. Twenty seven patients presented complete right bundle branch block associated with a left anterior hemiblock. The echocardiogram showed alteration in twelve patients. During the 24-hour Holter and ventricular stimulation, only one patient presented sustained ventricular tachycardia (SVT). Nine presented CVE during the study and only the HV interval &gt; 70ms presented a significant statistical relationship with CVE. CONCLUSIONS: a) The chronic form of Chagas disease presents different progressive abnormality percentages for the electrophysiological variables and WP alterations are the most common. b) Among the electrophysiological findings, only the HV interval &gt; 70ms was associated with CVE. c) The incidence of CVE was 31.1% during the average follow-up period of 154.5 months.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>electrophysiological studies</kwd>
        <kwd>cardiovascular events</kwd>
        <kwd>Chagas&#8217; disease</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ORIGINAL ARTICLE</bold>
      </p>
      <p>Serial electrophysiological studies of the heart&#146;s excito-conductor system in patients with chronic chagasic cardiopathy </p>
      <p>
        <bold>Ney Valente; Jo&#227;o Pimenta; Angelo Amato Vincenzo de Paola</bold>
      </p>
      <p>Hospital do Servidor P&#250;blico Estadual e Universidade Federal de S&#227;o Paulo - Unifesp - S&#227;o Paulo, SP - Brazil</p>
      <p>
        <xref ref-type="corresp" rid="end-body2">Mailing Address</xref>
      </p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p><bold>OBJECTIVES:</bold> To study the evolution of lesions in conduction system using invasive electrophysiological studies (EPS), the impact of these alterations on cardiovascular events (CVE), and the frequency of these events in chronic chagasic patients.</p>
      <p><bold>METHODS: </bold>Prospective study, initiated in 1979 with clinical follow-up until 2000, with the participation of 28 chronic chagasic patients that were 18 to 65 years old, with bundle branch and/or atrioventricular blocks. The patients were submitted to two EPS with a minimum interval of four years between the studies in order to assess five electrophysiologis parameters that were correlated with CVE. A 24-hour Holter and echocardiogram were performed.</p>
      <p><bold>RESULTS:</bold> The average follow-up time after the first EPS was 154.5 months while the interval between EPS was 107.5 months. Ages ranged from 25 to 65 years. Twenty seven patients presented complete right bundle branch block associated with a left anterior hemiblock. The echocardiogram showed alteration in twelve patients. During the 24-hour Holter and ventricular stimulation, only one patient presented sustained ventricular tachycardia (SVT). Nine presented CVE during the study and only the HV interval <underline>&gt;</underline> 70ms presented a significant statistical relationship with CVE.</p>
      <p><bold>CONCLUSIONS: </bold>a) The chronic form of Chagas disease presents different progressive abnormality percentages for the electrophysiological variables and WP alterations are the most common. b) Among the electrophysiological findings, only the HV interval <underline>&gt;</underline> 70ms was associated with CVE. c) The incidence of CVE was 31.1% during the average follow-up period of 154.5 months.</p>
      <p><bold>Key words:</bold> electrophysiological studies, cardiovascular events, Chagas&#146; disease</p>
      <p>Cardiovascular events (CVE) associated with Chagas disease such as SVT, sudden death, thromboembolism and late cardiac related death have been studied extensively.<sup>1-4</sup> The electrocardiogram (EKG) can show signs of significant myocardial damage, such as the presence of a complete right bundle branch block (RBBB) which may or may not be associated with a left anterior hemiblock (LAHB). The presence of inactive areas, complete left bundle branch block (LBBB), atrial fibrillation and ventricular tachyarrhythmia indicate a worse prognosis due to the extensive myocardial fibrosis found in these situations. </p>
      <p>The electrophysiological study (EPS) and the left ventricle angiography performed on symptomatic or asymptomatic patients, with or without conduction system disorders showed worse progression in chronic chagasic patients. This progression was related to myocardial dysfunction and to a lesser extent to the presence of conduction system disorders<sup>5</sup>, probably due to the fact that myocardial dysfunction is associated with the presence of complex ventricular arrhythmia.<sup>6</sup></p>
      <p>Various reports have been published in relation to repeated EPS on non-chagasic patients with follow-up of conduction system changes with a maximum interval of 35 months between the studies.<sup>7,8</sup> In relation to Chagas disease, there are no documented studies with repeated EPS on the same patients with long term follow-up that records the alterations of this exam with CVE. The objective of the present study was to evaluate the evolutionary behavior of lesions in the heart&#146;s excito conductor system using invasive EPS, the impact of these alterations on cardiovascular events (CVE), and the frequency of CVE in these patients over a prolonged follow-up period. </p>
      <p>
        <bold>METHODS</bold>
      </p>
      <p>This is a prospective study approved by the Ethics and Research Committee of the Institution. At the beginning of the study twenty-eight patients with the following characteristics were studied: all had at least two positive serological tests for Chagas disease, were between the ages of 18 and 65, had few or no symptoms for the NYHA functional class II, had no previous history of cardiopathies, had EKG alterations indicating bundle branch block or atrioventricular block, chest x-ray showed a cardiac silhouette within normal limits or with an increase of up to ++ (in 4+). An echocardiogram was performed during the 2<sup>nd</sup> EPS to observe myocardial contractibility and the ejection fraction. Myocardial contractibility was considered to be altered when any degree of diffused or segmental contractile abnormalities were detected. The ejection fraction was considered as altered when it was lower than 0.65. The 24-hour Holter EKG was also performed during the 2<sup>nd</sup> EPS in order to detect ventricular extrasystoles, SVT and nonsustained ventricular tachycardia (NSVT). </p>
      <p>All patients agreed in writing to be submitted to the EPS. The beginning of the study corresponded to the date of the first electrophysiological evaluation and the patients did not take any medications that could alter the evaluated measurements. Two EPS were performed using the techniques and normal values as previously described.<sup>9,10</sup> Values were considered elevated when they were above normal during 1<sup>st</sup> and 2<sup>nd</sup> EPS or when they increased from the 1<sup>st</sup> to the 2<sup>nd</sup> study. The findings of the HV interval were subdivided in greater than or equal to and less than 70 ms to evaluate the possibility of a group with a higher risk for CVE. Elevated values found during the 1<sup>st</sup> study that were within the normal range during the 2<sup>nd</sup> study, which was observed for the AH interval and the WP caused by vagal fluctuation, were considered normal. </p>
      <p>Ventricular stimulation was performed on all patients with extrastimulus until the refractory period was reached. A 24-hour Holter EKG and echocardiogram were performed during the 2<sup>nd</sup> EPS to observe arrhythmia and evaluate ventricular function, respectively (<xref ref-type="table" rid="tab01-body2">table I</xref>). Outpatient follow-up was made every three to six months, depending on the manifestation of symptoms. </p>
      <table-wrap id="tab01-body2">
        <graphic xlink:href="1678-4170-abc-86-01-0019-00004-gt01-en.jpg"/></table-wrap>
      <p>Statistical analysis was performed using the Fisher exact probability test and statistical significance was established as p &lt; 0.05. </p>
      <p>
        <bold>RESULTS</bold>
      </p>
      <p>The patients&#146; ages ranged from 25 to 65 years, an average of 42.3 years and a median of forty years during the 1<sup>st</sup> EPS and from 34 to 80 years, with an average of 52.2 years during the 2<sup>nd</sup> EPS. Sixteen of the patients were male. All patients except one presented a complete right bundle branch block (CRBBB), which was associated with a left anterior hemiblock (LAHB) in seventeen patients. One patient, the only one with normal QRS complexes, presented a type 1, 2<sup>nd</sup> degree AV block. The electrocardiograph pattern remained constant for the majority of patients during the study. The only significant change was the development of a total AV block in two patients, one who had CRBBB during the 1<sup>st</sup> EPS and the other who had CRBBB associated with a LAHB during the 1<sup>st</sup> EPS. One patient who had a type 1, 2<sup>nd</sup> degree AV block without an intraventricular conduction disorder developed CRBBB without any deterioration of the AV block. The average interval between the studies was 107.5 (50 to 199) months and the average follow-up duration after the 1<sup>st</sup> EPS was 154.5 (81 to 233) months. </p>
      <p><italic><bold>Cardiovascular Events </bold></italic>- Cardiovascular events affected nine patients (31.1%). Four suffered sudden death, four had ischemic strokes, one had SVT, one had a pulmonary embolism and three suffered cardiac related deaths. One patient presented an ischemic stroke and sudden death and those that suffered cardiac related deaths also suffered from another CVE (pulmonary embolism, SVT and ischemic stroke)prior to death. The data collected during the 1<sup>st</sup> EPS and the CVE are shown in <xref ref-type="table" rid="tab02-body2">table II</xref>. <xref ref-type="fig" rid="fig01-body2">Figure 1</xref> shows the alterations of the 1<sup>st</sup> and 2<sup>nd</sup> EPS and the respective proportions of increase.</p>
      <table-wrap id="tab02-body2">
        <graphic xlink:href="1678-4170-abc-86-01-0019-00004-gt02-en.jpg"/></table-wrap>
      <fig id="fig01-body2">
        <graphic xlink:href="1678-4170-abc-86-01-0019-00004-gf01-en.jpg"/></fig>
      <p><italic><bold>Echocardiogram</bold></italic> - Myocardial contractibility was normal in sixteen patients and abnormal in twelve with diffused hypokinesia in seven and segmental hypokinesia in five. Of these, four were infero-basal and one antero-apical. (<xref ref-type="table" rid="tab01-body2">table I</xref>) </p>
      <p><italic><bold>24-hour Holter </bold></italic>- Just one patient had SVT and nine had NSVT. Fourteen patients had ventricular extrasystoles &gt; 30/ h and &lt; 30/ h. (<xref ref-type="table" rid="tab01-body2">table I</xref>). </p>
      <p><italic><bold>Electrophysiological Study</bold></italic> - AH interval &#150; Five patients (17.8%) presented increases, four (14.2%) during the 1<sup>st</sup> study and two presented nonsustained CVE. The percentage of increases between the 1<sup>st</sup> and 2<sup>nd</sup> EPS was 4.16%. (<xref ref-type="table" rid="tab02-body2">table II</xref>).</p>
      <p>HV interval &#150; Six patients (21.4%) presented increases, two during the 1<sup>st</sup> study and four presented nonsustained CVE. The percentage of increases between the 1<sup>st</sup> and 2<sup>nd</sup> EPS was 15.38%. Five patients (17.8%) presented an HV interval <underline>&gt;</underline>70 ms, four with CVE (p = 0.025). (<xref ref-type="table" rid="tab02-body2">table II</xref>)</p>
      <p>Corrected sinus node recovery time &#150; Increased in six patients (21.4%), three during the 1<sup>st</sup> study and one presented nonsustained CVE. The percentage of increases between the 1<sup>st</sup> and 2<sup>nd</sup> EPS was 12%. (<xref ref-type="table" rid="tab02-body2">table II</xref>)</p>
      <p>Wenckebach Phenomenon &#150; Increased in eleven patients (39.2%), seven during the 1<sup>st</sup> study and four presented nonsustained CVE. The percentage of increases between the 1<sup>st</sup> and 2<sup>nd</sup> EPS was 19.04%. (<xref ref-type="table" rid="tab02-body2">table II</xref>).</p>
      <p>Alterations in the AV node function curve &#150; Present in six patients (21.4%), four (14.3%) during the 1<sup>st</sup> study and just one presented nonsustained CVE. The percentage of new cases with this alteration was 8.3%. (<xref ref-type="table" rid="tab02-body2">table II</xref>). </p>
      <p>Ventricular stimulation &#150; One patient presented SVT and five had repetitive heartbeats (<xref ref-type="table" rid="tab02-body2">table II</xref>).</p>
      <p>
        <bold>DISCUSSION</bold>
      </p>
      <p>The progression of chronic chagasic cardiopathy is usually prolonged, however CVE often hasten this process. These complications are frequently associated with a histological substrate showing myocardial fiber degeneration and fibroblast proliferation with the formation of small fibrous plaques that are distributed by the myocardium. To compensate for the functional deficiency of the myocardial fibers and to maintain circulatory dynamics, the ventricles dilate.<sup>11</sup> Consequently, the size of the heart in chronic chagasic cardiomyopathy is closely related to the degree of myocardial lesion attributing to a higher incidence of CVE caused by arrhythmia<sup>12-14</sup> and thromboembolism.</p>
      <p>Recently three-dimensional confocal microscopes have been used to detect severe diffused dilation and deformities of the arterioles which cause a perfusion of tissue that is detrimental to patients, who have had multiple heart attacks. The resulting areas of fibrosis can also cause vessel trajectory obstructions causing ischemic lesions.<sup>17</sup> Another study directly related myocardial dysfunction to the amount of interstitial myocardial collagen.<sup>18</sup></p>
      <p>The EPS is an important method to detail possible excito conductor system alterations in Chagas disease. Similarly, the significance of the AH interval was studied in non-chagasic patients with CRBBB associated with LAHB which revealed that an increase in this interval causes a higher incidence of organic heart disease and myocardial dysfunction.<sup>19</sup> Irregardless, follow-up during a three year period did not reveal any statistical differences in relation to the number of sudden deaths and overall mortality when compared to patients with normal and increased AH intervals. In this study, an increase in the AH interval was seen in 17.8% of the patients, which is similar to the percentages seen in non-chagasic patients<sup>19-21</sup> with no significant statistical relationship between CVE and AH interval values. Three patients presented normalization of the AH interval during the 2<sup>nd</sup> EPS probably due to vagal fluctuation. </p>
      <p>A higher number of individuals presented a WP increase, confirming this frequent alteration in Chagas disease, which appears to be more sensitive in the identification of the conduction node disorders since the value was altered in various patients with a normal AH interval. Only four individuals presented CVE which did not have a significant statistical relationship with the increase of WP. </p>
      <p>Conduction disorders in the His-Purkinje system are common in chagasic patients and are usually the cause of total AV block. Various studies on non-chagasic patients related an increase of the HV interval and cardiac events.<sup>19,22,23</sup> One study evaluated 517 non-chagasic individuals with a bifascicular block and an average follow-up period of 3.4 years, revealed a relationship between a prolonged HV interval and a higher incidence and severity of organic heart disease, noting that heart failure was more common with an advanced functional class rating, angina pectoris or a prior myocardial infarction.<sup>22</sup> Additionally, overall mortality and sudden death were significantly more common in the group with an increased HV interval. Two other studies with durations of three years and eight months, respectively, confirmed a higher incidence of AV block and mortality in non-chagasic individuals with these alterations.<sup>19,23</sup> However, other observations<sup>24,25</sup> did not reproduce these results. In this study of chagasic patients, the correlation between CVE and an increased HV interval was only statistically significant when calculated with HV interval values that were greater than or equal to 70ms. </p>
      <p>Sinus node recovery time can be affected by age, associated diseases, methods employed and to a great extent by the length of the rest cycle which is why the CSNRT was used. Comparison between non-chagasic patients with bifascicular or trifascicular blocks and others with normal QRS complexes showed that the first group had a much higher percentage of electrophysiological sinus node and atrium abnormalities.<sup>26</sup> In chagasic individuals, the sinus node function was evaluated in various studies revealing variable CSNRT alteration percentages depending on the symptoms, form of disease (determined or not), the evaluation with or without an autonomic block or caused by the isolated use of atropine.<sup>5,10,27-32</sup> The mechanism of the sinus dysfunction is frequently a combination of impairment of automatism and sinoatrial conduction . Individuals with chronic Chagas disease, with or without heart failure, have significant CSNRT abnormalities ranging from 18.1% to 45%,<sup>10,31,32</sup> with the lower percentages noted in asymptomatic patients. A study of asymptomatic chronic chagasic patients with CRBBB and non-chagasic patients with CRBBB or a complete left bundle branch block revealed that an alteration in the CSNRT was an important indicator of symptomatic sinus node dysfunction; however, there was only a correlation with cardiac related mortality in non-chagasic individuals.<sup>33</sup> In this study the incidence of CSNRT alterations were proportionally similar to lower results documented in medical literature which could be due to the large number of asymptomatic patients in the sample. The relation of an alteration in this parameter with CVE did not show any statistical significance.</p>
      <p>At the end of the study the incidence of CVE was 31.1%. The pathophysiology of sudden death is unknown but it has been identified that chronic fibrous myocarditis, initiated and perpetrated by alterations in myocardial microcirculation and auto-immune factors, combined with autonomic nervous system lesions and left ventricular dysfunction dramatically increase the risk. A recent revision reaffirms sudden death warning signs, indicating heart rate variations and QT interval dispersion analysis as new methods of risk stratification.<sup>35</sup> None of the patients that suffered from sudden death had presented signs of decompensated heart failure, reinforcing the hypothesis that the cause was cardiac arrhythmia.</p>
      <p>Pulmonary and systemic thromboembolisms are common in Chagas disease.<sup>4,15</sup> Generally speaking, in pulmonary thromboembolisms the embolism originates from intracavity thrombosis and not peripheral venous thrombosis. Systemic thromboembolisms are usually found in the kidneys and spleen and rarely in the brain<sup>4,15</sup> and therefore are more common in the case of an apical lesion.<sup>36</sup> In this study, four of the five thromboembolism cases were located in the brain and one in the lungs. This fact could be related to the small number of patients with decompensated heart failure which is a prerequisite for pulmonary embolism. </p>
      <p>SVT indicates the seriousness of Chagas disease, with a five year mortality rate of almost 100%.<sup>37</sup> SVT that is induced by programmed ventricular stimulation is an important indicator of cardiac death due to arrhythmia and overall mortality in patients with nonsustained ventricular tachycardia.<sup>38</sup> Patients that present SVT with hemodynamic repercussions have worse prognoses than those that are asymptomatic or do not have SVT.<sup>39</sup> It is predominately located in the basal region followed by the septal and apical regions<sup>40</sup>, and is the arrhythmia reentrance mechanism <sup>41</sup>. In the group studied, only one patient presented SVT during the 24-hour Holter test and EPS possibly due to the large number of asymptomatic patients and also since the protocols of ventricular stimulation at the beginning of the study were less aggressive due to ethical problems. </p>
      <p>A cardiac related death could be caused by congestive heart failure (CHF) however more common causes are malignant ventricular tachyarrhythmia or pulmonary embolisms. The three patients in this study that died from CHF had a prior history of CVE, pulmonary embolism, SVT or ischemic stroke. </p>
      <p>Therefore, evolutionary alterations in the heart&#146;s excito conduction system are slow, progressive, and diffused which allows the identification of the seriousness and frequency of the damage to each segment, revealing which ones are related to CVE. This is valuable information for the patients, allowing a more rigorous follow-up and more frequent clinical and laboratory tests for those with the worst prognoses.</p>
      <p>
        <bold>REFERENCES</bold>
      </p>
      <p>1. Bestetti RB, Dalbo CM, Arruda CA, Correia Filho D, Freitas OC. Predictors of sudden cardiac death for patients with Chagas&#146; disease: a hospital-derived cohort study. Cardiology 1996; 87: 481-7.</p>
      <p>2. De Paola AAV. Estimula&#231;&#227;o ventricular programada em pacientes com cardiopatia chag&#225;sica cr&#244;nica e taquicardia ventricular. S&#227;o Paulo, 1990. Tese (Livre-Doc&#234;ncia) &#150; Escola Paulista de Medicina.</p>
      <p>3. Espinosa RA, Carrasco HA, Belandria F, Fuenmayor AM, Molina C, Gonz&#225;lez R et al. Life expectancy analysis in patients with Chagas&#146; disease: Prognosis after one decade (1973-1983). Int J Cardiol 1985; 8: 45-56.</p>
      <p>4. Arteaga-Fernandez E, Barreto ACP, Ianni BM, Mady C, Lopez EA, Vianna CB et al. Trombose card&#237;aca e embolia em pacientes falecidos de cardiopatia chag&#225;sica cr&#244;nica. Arq Bras Cardiol 1989; 52: 189-92.</p>
      <p>5. Benchimol CB, Ginefra P, Benchimol AB. Avalia&#231;&#227;o eletrofisiol&#243;gica. In: Can&#231;ado JR, Chuster M.: Cardiopatia chag&#225;sica. Belo Horizonte: Funda&#231;&#227;o Carlos Chagas de Pesquisas M&#233;dicas, 1985, 213-22.</p>
      <p>6. Carrasco HA, Gerrero L, Parada H, Molia C, Vegas E, Chuecos R. Ventricular arrhythmias and left ventricular myocardial function in chronic chagasic patients. Int J Cardiol 1990; 28: 35-41.</p>
      <p>7. Peters RW, Scheinman MM, Dhingra R, Rosen K, McAnulty J, Rahimtoola SH et al. Serial electrophysiological studies in patients with chronic bundle branch block. Circulation 1982; 65: 1480-5.</p>
      <p>8. Prystowsky EN, Pritchett ELC, Roses AD, Gallagher J. The natural history of conduction system disease in myotonic muscular dystrophy, as determined by serial electrophysiological studies. Circulation 1979; 60: 1360-4.</p>
      <p>9. Scherlag BJ, Lau SH, Helfant RH, Berkowitz WD, Stein E, Damato NA. Catheter technique for recording His bundle activity in man. Circulation 1969; 39: 13-8.</p>
      <p>10. Pimenta J, Miranda M, Pereira CB. Electrophysiological findings in long-term asymptomatic chagasic individuals. Am Heart J 1983; 106: 374-80.</p>
      <p>11. Anselmi A, Pifano F, Suarez JA, Gurdiel O, Lapco L. Cardiovascular radiology in acute and chronic Chagas&#146; myocardiopathy. Morphologic and dynamic study of the cardiac contour, correlated with the histological changes observed in myocardiopathies attributed to Schizotrypanum cruzi. Am Heart J 1967; 73: 626-39.</p>
      <p>12. Carrasco HA, Parada H, Gerrero L, Duque M, Duran D, Molina C. Prognostic implications of clinical, electrocardiographic, and hemodynamic findings in chronic Chagas&#146; disease. Int J Cardiol 1994; 43: 27-38.</p>
      <p>13. Bestetti RB, Muccillo G. Clinical course of Chagas&#146; heart disease: A comparison with dilated cardiomyopathy. Int J Cardiol 1997; 60: 187-93.</p>
      <p>14. Barreto ACP, Bellotti G, Deperon SD, Arteaga-Fernandez E, Mady C, Ianni BM et al. O valor do eletrocardiograma na avalia&#231;&#227;o da fun&#231;&#227;o mioc&#225;rdica dos portadores de doen&#231;a de Chagas. Arq Bras Cardiol 1989; 52: 69-73.</p>
      <p>15. Oliveira JSM, Araujo RRC, Navarro MA, Muccillo G. Cardiac thrombosis and thromboembolism in chronic Chagas&#146; heart disease. Am J Cardiol 1983; 52: 147-51.</p>
      <p>16. Elian AA. Aspectos cl&#237;nicos do tromboembolismo. In Can&#231;ado SR, Chuster M. Cardiopatia chag&#225;sica . Belo Horizonte: Funda&#231;&#227;o Carlos Chagas, 1985, 314-22.</p>
      <p>17. Higuchi ML, Fukasawa S, De Brito T, Parzianello LC, Bellotti G, Ramires JAF. Different microcirculatory and interstitial matrix patterns in idiopathic dilated cardiomyopathy and Chagas&#146; disease: a three dimensional confocal microscopy study. Heart 1999; 82: 279-85.</p>
      <p>18. Mady C, Ianni BM, Arteaga E, Montes GS, Caldini EG, Andrade G et al. Relation between interstitial myocardial collagen and the degree of clinical impairment in Chagas&#146; disease. Am J Cardiol 1999; 84: 354-6.</p>
      <p>19. Dhingra RC, Wyndham C, Amat-Y-Leon F, Wu D, Denes P, Towne WD et al. Significance of A-H interval in patients with chronic bundle branch block. Clinical, electrophysiological and follow-up observations. Am J Cardiol 1976; 37: 231-6.</p>
      <p>20. Narula OS, Samet P. Right bundle branch block with normal left or right axis deviation. Analysis by His bundle recordings. Am J Med 1971; 51: 432-55. </p>
      <p>21. Levites R, Haft JL. Significance of first degree heart block (prolonged P-R interval) in bifascicular block. Am J Cardiol 1974; 34: 259-64.</p>
      <p>22. Dhingra RC, Lalileo E, Strasberg B, Swiryn S, Bauernfeind RA, Wyndham CRC et al. Significance of the HV interval in 517 patients with chronic bifascicular block. Circulation 1981; 64:1265-71.</p>
      <p>23. Scheinman M, Weiss A, Kunfel F. His bundle recording in patients with bundle branch block and transient neurologic symptoms. Circulation 1973; 48: 322-30.</p>
      <p>24. Denes P, Dhingra RC, Wu D, Chuquimia R, Amat-Y-Leon F, Wyndham C et al. H-V interval in patients with bifascicular block (right bundle branch block and left anterior hemiblock). Am J Cardiol 1975; 35: 23-9.</p>
      <p>25. McAnulty JH, Rahimtoola SH, Murphy E, Demots H, Ritzmann L, Kanarek PE et al. Natural history of "high-risk" bundle branch block. Final report of a prospective study. N Engl J Med 1982; 307: 137-43. </p>
      <p>26. Wise DG, McAnulty JH, Rahimtoola SH, Murphy ES. Electrophysiological abnormalities of the sinus node and atrium in patients with bundle branch block. Circulation 1979; 60: 413-20.</p>
      <p>27. Sosa EA. Contribui&#231;&#227;o ao estudo da condu&#231;&#227;o &#225;trio-ventricular na forma cr&#244;nica indeterminada da doen&#231;a de Chagas. S&#227;o Paulo, 1977. Disserta&#231;&#227;o (Mestrado) - Faculdade de Medicina, Universidade de S&#227;o Paulo.</p>
      <p>28. Sosa EA. Contribui&#231;&#227;o para o estudo das propriedades eletrofisiol&#243;gicas do cora&#231;&#227;o na doen&#231;a de Chagas. S&#227;o Paulo, 1979. Tese (Doutorado) - Faculdade de Medicina, Universidade de S&#227;o Paulo.</p>
      <p>29. Benchimol CB, Kreuzig R, Ginefra P, Schlesinger P, Benchimol AB. A disfun&#231;&#227;o do n&#243;dulo sinusal na cardiopatia chag&#225;sica cr&#244;nica. Arq Bras Cardiol 1977; 30: 337-44.</p>
      <p>30. Benchimol CB. Disfun&#231;&#227;o do n&#243;dulo sinusal na doen&#231;a de Chagas. Contribui&#231;&#227;o cl&#237;nica, eletrofisiol&#243;gica e farmacol&#243;gica. Correla&#231;&#227;o com a hemodin&#226;mica e cineangiocardiografia do ventr&#237;culo esquerdo. Rio de Janeiro 1981. Tese (Doutorado) -- Universidade Federal do Rio de Janeiro.</p>
      <p>31. Maia IG, S&#225; RS, Loyola LHC, Ara&#250;jo PP, Monteiro SM, Amino JGC et al. O n&#243;dulo sinusal na cardiopatia chag&#225;sica cr&#244;nica. Arq Bras Cardiol 1983; 40: 91-6.</p>
      <p>32. Carrasco HA, Mora R, Inglessis G, Contreras JM, Marval J, Fuenmayor A. Estudio de la funci&#243;n del nodo sinusal y de la conducci&#243;n atrioventricular en pacientes con enfermedad de Chagas. Arch Inst Cardiol Mex 1982; 52: 245-51.</p>
      <p>33. Pimenta J, Valente N, Miranda M. Evolu&#231;&#227;o cl&#237;nica a longo prazo, correlacionando a presen&#231;a de bloqueios da condu&#231;&#227;o intraventricular em pacientes chag&#225;sicos e n&#227;o chag&#225;sicos assintom&#225;ticos. Rev Soc Bras Med Trop 1999; 32: 621-31.</p>
      <p>34. Rossi MA, Bestetti RB. The challenge of chagasic cardiomyopathy. The pathologic roles of autonomic abnormalities, autoimmune mechanisms and microvascular changes and therapeutic implications. Cardiology 1995; 86: 1-7.</p>
      <p>35. Rassi Jr A, Rassi SG, Rassi A. Morte s&#250;bita na doen&#231;a de Chagas. Arq Bras Cardiol 2001; 76: 75-85.</p>
      <p>36. Silva F, Marins N, Kagami SK, Silva CT, Motta VP, Barbosa PH. Acidentes c&#233;rebro-vasculares tromboemb&#243;licos e miocardiopatia chag&#225;sica. Arq Bras Cardiol 1979; 32: 45-9.</p>
      <p>37. Rassi A, Lorga AM, Rassi S. Abordagem diagn&#243;stica e terap&#234;utica das arritmias na cardiopatia chag&#225;sica cr&#244;nica. In Germiniani H. Diagn&#243;stico e terap&#234;utica das arritmias card&#237;acas. 3&#170; ed. Rio de Janeiro: Editora Guanabara, 1990, 225-44.</p>
      <p>38. Silva RMFL, Tavora MZP, Gondim FAA, Metha N, Hara VM, Paola AAV. Valor preditivo das vari&#225;veis cl&#237;nicas e eletrofisiol&#243;gicas em pacientes com miocardiopatia chag&#225;sica cr&#244;nica e taquicardia ventricular n&#227;o-sustentada. Arq Bras Cardiol 2000; 75: 33-47.</p>
      <p>39. Leite LR, Fenelon G, Sim&#245;es S. Jr, Silva GG, Friedman PA, de Paola AA. Clinical usefulness of electrophysiological testing in patients with ventricular tachycardia and chronic chagasic cardiomyopathy treated with amiodarone or sotalol. J Cardiovasc Electrophysiol 2003; 14: 567-73.</p>
      <p>40. Takehara K, Scanavaca M, Sosa EA, Lopes E, Marcial MB, Consolim FM et al. Aspectos anatomopatol&#243;gicos do foco da taquicardia ventricular sustentada recorrente da miocardiopatia chag&#225;sica cr&#244;nica. Arq Bras Cardiol 1990; 55: B-68. (Abstract)</p>
      <p>41. Milei J, Pesce R, Valero E, Muratore C, Beigelman R, Ferrans VJ. Electrophysiological-structural correlations in chagasic aneurysm causing malignant arrhythmias. Int J Cardiol 1991; 32: 65-74.</p>
      <p>
        <fn id="end-body2" fn-type="corresp">
          <label>
            <bold>Mailing Address</bold>
          </label>
          <p> Ney Valente</p>
          <p> Rua 1&#186; de Mar&#231;o, 193</p>
          <p> 04044-040 &#150; S&#227;o Paulo, SP - Brazil</p>
          <p> E-mail: </p>
          <p>
            <email xlink:href="pimenta@cardiol.br">pimenta@cardiol.br</email>
          </p>
        </fn>
      </p>
      <p>Received on 02/01/04</p>
      <p> Accepted on 05/18/05</p>
    </body>
  </sub-article>
</article>
