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  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
        <publisher-loc>S&#227;o Paulo, SP, Brazil</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">ycFvBP6cqnd7vNpGLvc8dnH</article-id>
      <article-id pub-id-type="other">00008</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2005000200008</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(05)08400208</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2005000200008</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Determina&#231;&#227;o do pept&#237;deo natriur&#233;tico cerebral humano em portadores da doen&#231;a de Chagas</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Melo</surname>
            <given-names>Railton Bezerra de</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Parente</surname>
            <given-names>Giordano Bruno de Oliveira</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Victor</surname>
            <given-names>Edgar Guimar&#227;es</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <institution content-type="orgname">UFP</institution>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>02</month>
        <year>2005</year>
      </pub-date>
      <volume>84</volume>
      <issue>2</issue>
      <fpage>137</fpage>
      <lpage>140</lpage>
      <history>
        <date date-type="received">
          <day>02</day>
          <month>02</month>
          <year>2004</year>
        </date>
        <date date-type="accepted">
          <day>07</day>
          <month>04</month>
          <year>2004</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/" xml:lang="en">
          <license-p>This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.</license-p>
        </license>
      </permissions>
      <abstract>
        <p>OBJETIVO: Determinar os n&#237;veis s&#233;ricos do pept&#237;deo natriur&#233;tico cerebral (PNB) em pacientes com cardiopatia chag&#225;sica cr&#244;nica e em indiv&#237;duos com sorologia positiva para doen&#231;a de Chagas sem comprometimento card&#237;aco, e correlacionar os n&#237;veis de PNB com o grau de comprometimento card&#237;aco, dimens&#245;es card&#237;acas, presen&#231;a de marcapasso e fra&#231;&#227;o de eje&#231;&#227;o. M&#201;TODOS: Concentra&#231;&#245;es s&#233;ricas de PNB foram determinadas atrav&#233;s do Triage&#174; - BNP Test, produzido pela BIOSITE&#174;. Foi avaliado o PNB s&#233;rico de 25 indiv&#237;duos do ambulat&#243;rio de doen&#231;a de Chagas do Hospital Universit&#225;rio Oswaldo Cruz, distribu&#237;dos em 2 grupos, um, G1; composto por 13 portadores de sorologia positiva para doen&#231;a de Chagas, assintom&#225;ticos e sem cardiopatia detect&#225;vel pelo eletrocardiograma, radiografia do t&#243;rax e ecocardiograma, o outro, G2; por 12 portadores da doen&#231;a de Chagas com comprometimento card&#237;aco. RESULTADOS: N&#237;veis significativamente mais elevados de PNB foram detectados nos pacientes chag&#225;sicos com comprometimento card&#237;aco: (G1=4,4&#177;4,4 pg/ml, G2=293,0&#177;460,2 pg/ml) p&lt;0,01. Nos 2 grupos n&#227;o houve correla&#231;&#227;o dos n&#237;veis s&#233;ricos de PNB com a idade e o sexo. Os n&#237;veis foram diretamente proporcionais &#224; classe funcional e &#224; &#225;rea card&#237;aca no estudo radiol&#243;gico do t&#243;rax. Apesar de demonstrar uma tend&#234;ncia de eleva&#231;&#227;o no comprometimento da fun&#231;&#227;o sist&#243;lica, n&#227;o houve correla&#231;&#227;o linear com a fra&#231;&#227;o de eje&#231;&#227;o ao ecocardiograma. Presen&#231;a de marcapasso definitivo e altera&#231;&#245;es eletrocardiogr&#225;ficas n&#227;o modificaram os n&#237;veis s&#233;ricos de PNB. CONCLUS&#195;O: Os indiv&#237;duos com sorologia positiva para doen&#231;a de Chagas, assintom&#225;ticos e sem evid&#234;ncia de disfun&#231;&#227;o ventricular, possuem n&#237;veis s&#233;ricos de PNB semelhantes aos da popula&#231;&#227;o em geral.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>doen&#231;a de Chagas</kwd>
        <kwd>pept&#237;deos natriur&#233;ticos</kwd>
        <kwd>pept&#237;deo natriu r&#233;tico cerebral</kwd>
        <kwd>insufici&#234;ncia card&#237;aca congestiva</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>08</day>
        <month>03</month>
        <year>2005</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>ARTIGO ORIGINAL</bold>
    </p>
    <p>Determina&#231;&#227;o do pept&#237;deo natriur&#233;tico cerebral humano em portadores da doen&#231;a de Chagas  </p>
    <p>Railton Bezerra de Melo; Giordano Bruno de Oliveira Parente; Edgar Guimar&#227;es Victor </p>
    <p>Recife, PE</p>
    <p>Programa de P&#243;s Gradua&#231;&#227;o em Medicina Interna - UFP </p>
    <p>
      <xref ref-type="corresp" rid="end">Endere&#231;o para correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>OBJETIVO:</bold> Determinar os n&#237;veis s&#233;ricos do pept&#237;deo natriur&#233;tico cerebral (PNB) em pacientes com cardiopatia chag&#225;sica cr&#244;nica e em indiv&#237;duos com sorologia positiva para doen&#231;a de Chagas sem comprometimento card&#237;aco, e correlacionar os n&#237;veis de PNB com o grau de comprometimento card&#237;aco, dimens&#245;es card&#237;acas, presen&#231;a de marcapasso e fra&#231;&#227;o de eje&#231;&#227;o. </p>
    <p><bold>M&#201;TODOS: </bold> Concentra&#231;&#245;es s&#233;ricas de PNB foram determinadas atrav&#233;s do Triage<sup>&#174;</sup> - BNP Test, produzido pela BIOSITE<sup>&#174;</sup>. Foi avaliado o PNB s&#233;rico de 25 indiv&#237;duos do ambulat&#243;rio de doen&#231;a de Chagas do Hospital Universit&#225;rio Oswaldo Cruz, distribu&#237;dos em 2 grupos, um, G1; composto por 13 portadores de sorologia positiva para doen&#231;a de Chagas, assintom&#225;ticos e sem cardiopatia detect&#225;vel pelo eletrocardiograma, radiografia do t&#243;rax e ecocardiograma, o outro, G2; por 12 portadores da doen&#231;a de Chagas com comprometimento card&#237;aco. </p>
    <p><bold>RESULTADOS: </bold>N&#237;veis significativamente mais elevados de PNB foram detectados nos pacientes chag&#225;sicos com comprometimento card&#237;aco: (G1=4,4&#177;4,4 pg/ml, G2=293,0&#177;460,2 pg/ml) p&lt;0,01. Nos 2 grupos n&#227;o houve correla&#231;&#227;o dos n&#237;veis s&#233;ricos de PNB com a idade e o sexo. Os n&#237;veis foram diretamente proporcionais &#224; classe funcional e &#224; &#225;rea card&#237;aca no estudo radiol&#243;gico do t&#243;rax. Apesar de demonstrar uma tend&#234;ncia de eleva&#231;&#227;o no comprometimento da fun&#231;&#227;o sist&#243;lica, n&#227;o houve correla&#231;&#227;o linear com a fra&#231;&#227;o de eje&#231;&#227;o ao ecocardiograma. Presen&#231;a de marcapasso definitivo e altera&#231;&#245;es eletrocardiogr&#225;ficas n&#227;o modificaram os n&#237;veis s&#233;ricos de PNB. </p>
    <p><bold>CONCLUS&#195;O: </bold>Os indiv&#237;duos com sorologia positiva para doen&#231;a de Chagas, assintom&#225;ticos e sem evid&#234;ncia de disfun&#231;&#227;o ventricular, possuem n&#237;veis s&#233;ricos de PNB semelhantes aos da popula&#231;&#227;o em geral. </p>
    <p><bold>Palavras-chave:</bold> doen&#231;a de Chagas, pept&#237;deos natriur&#233;ticos, pept&#237;deo natriu r&#233;tico cerebral, insufici&#234;ncia card&#237;aca congestiva</p>
    <p> Estima-se que 16 a 18 milh&#245;es de pessoas est&#227;o infectados na Am&#233;rica Latina<sup>1</sup>, sendo a doen&#231;a de Chagas a 4&#170; causa de maior dano entre as doen&#231;as transmiss&#237;veis na Am&#233;rica e, no Brasil, 6 a 8 milh&#245;es de infectados<sup>2</sup>. A cardiopatia chag&#225;sica pode se manifestar de diversas formas, podendo o indiv&#237;duo estar assintom&#225;tico e sem evid&#234;ncias de envolvimento card&#237;aco, ser portador de miocardiopatia com insufici&#234;ncia card&#237;aca e de arritmias card&#237;acas diversas. </p>
    <p>J&#225; foi bem demonstrado que pacientes com insufici&#234;ncia card&#237;aca congestiva t&#234;m altas concentra&#231;&#245;es s&#233;ricas de PNA e pept&#237;deo natriur&#233;tico cerebral (PNB) e que estes n&#237;veis se correlacionam com a extens&#227;o da disfun&#231;&#227;o ventricular, aumentando numa propor&#231;&#227;o de 30 vezes em pacientes com doen&#231;a card&#237;aca avan&#231;ada. As concentra&#231;&#245;es altas tamb&#233;m s&#227;o preditoras de curta sobrevida, correlacionando-se mais intimamente com o progn&#243;stico<sup>3-5</sup>. </p>
    <p>Em decorr&#234;ncia da import&#226;ncia do PNB como marcador de gravidade e de mortalidade em v&#225;rias doen&#231;as, principalmente em cardiopatias, justifica-se a determina&#231;&#227;o dos n&#237;veis s&#233;ricos deste pept&#237;deo na doen&#231;a de Chagas. Prov&#225;veis altera&#231;&#245;es dos n&#237;veis de PNB podem estar envolvidas de acordo com as fases cl&#237;nicas da doen&#231;a. Esta t&#233;cnica poder&#225; fornecer subs&#237;dios para formular estrat&#233;gias terap&#234;uticas mais adequadas segundo o perfil bioqu&#237;mico do paciente. </p>
    <p>
      <bold>M&#233;todos</bold>
    </p>
    <p>Os participantes do estudo foram oriundos do ambulat&#243;rio de doen&#231;a de Chagas do Hospital Universit&#225;rio Oswaldo Cruz da Universidade de Pernambuco, recrutados por carta a participarem do estudo. </p>
    <p>A popula&#231;&#227;o do estudo foi composta de 25 indiv&#237;duos divididos em 2 grupos: o 1&#186; grupo (G1) composto de 13 indiv&#237;duos encaminhados por institui&#231;&#227;o de hemoterapia por terem sorologia positiva para doen&#231;a de Chagas. Indiv&#237;duos que n&#227;o apresentavam comprometimento card&#237;aco, verificado atrav&#233;s de aus&#234;ncia de sintomatologia cl&#237;nica e nenhuma altera&#231;&#227;o sugestiva de cardiopatia ao eletrocardiograma, radiografia do t&#243;rax e ecodopplercardiograma. O 2&#186; grupo (G2) constitu&#237;do de 12 portadores da forma card&#237;aca cr&#244;nica da doen&#231;a de Chagas, que eram acompanhados naquele ambulat&#243;rio; indiv&#237;duos sororeagentes para doen&#231;a de Chagas e que apresentavam comprometimento card&#237;aco (presen&#231;a de sintomatologia e altera&#231;&#227;o compat&#237;vel com cardiopatia chag&#225;sica ao eletrocardiograma, &#224; radiografia do t&#243;rax e/ou ao ecodopplercardiograma). </p>
    <p>Foram utilizadas as t&#233;cnicas de hemaglutina&#231;&#227;o indireta e imunofluoresc&#234;ncia indireta nos dois grupos para confirma&#231;&#227;o sorol&#243;gica da doen&#231;a de Chagas. </p>
    <p>Os crit&#233;rios de exclus&#227;o foram: portadores de qualquer outra doen&#231;a card&#237;aca ou sist&#234;mica; uso de medica&#231;&#227;o n&#227;o cardiol&#243;gica que pudesse alterar significativamente os n&#237;veis de PNB; estados fisiol&#243;gicos que pudessem modificar significativamente os n&#237;veis de PNB, tais como gravidez; idade inferior a 18 anos ou incapacidade mentalmente. </p>
    <p>Ap&#243;s a coleta da amostra sang&#252;&#237;nea, foram utilizadas micropipetas transferidoras dispon&#237;veis juntamente com o "KIT" do PNB, e o conte&#250;do destas adicionados ao <italic>Triage</italic><sup>&#174;</sup><italic> BNP Test Device </italic>em temperatura ambiente. </p>
    <p>Foram estudadas as variav&#233;is: idade, sexo, classe funcional da insufici&#234;ncia card&#237;aca (NYHA), uso de medicamentos, presen&#231;a de marcapasso, altera&#231;&#245;es eletrocardiogr&#225;ficas, radiogr&#225;ficas e ecocardiogr&#225;ficas </p>
    <p>Os par&#226;metros ecocardiogr&#225;ficos analisados foram: as dimens&#245;es, espessura e volumes das cavidades card&#237;acas, as caracter&#237;sticas da contratilidade regional e global do ventr&#237;culo esquerdo e, as ondas de fluxo por Doppler, derivando-se da&#237; a fun&#231;&#227;o e diast&#243;lica do ventr&#237;culo esquerdo. Caso a fun&#231;&#227;o sist&#243;lica (avaliada pelo m&#233;todo de Simpson) estivesse diminu&#237;da, o comprometimento era classificado em leve, moderado e grave. Foram pesquisadas as altera&#231;&#245;es estruturais e a mobilidade das valvas card&#237;acas al&#233;m da presen&#231;a de trombo intracavit&#225;rio. </p>
    <p>Como as amostras estudadas apresentaram distribui&#231;&#227;o acentuadamente assim&#233;trica os grupos foram comparados atrav&#233;s do teste n&#227;o-param&#233;trico de Kruskal-Wallis. </p>
    <p>O presente estudo foi aprovado pelo Comit&#234; de &#201;tica do HUOC-UPE, que segue as normas contidas na resolu&#231;&#227;o 196/96 do Conselho Nacional de Sa&#250;de. Ap&#243;s serem informados mais detalhadamente sobre a pesquisa, todos os pacientes assinaram termo de consentimento livre e esclarecido. </p>
    <p>
      <bold>Resultados</bold>
    </p>
    <p>A popula&#231;&#227;o total do estudo foi constitu&#237;da por 25 pacientes divididos em dois grupos: o G1 com 13 indiv&#237;duos sendo 7 homens (69,2 %) e 6 mulheres (30,8 %) e o G2 com 12 participantes sendo a metade de mulheres e com uma m&#233;dia de idade maior que o G1 (62,7&#177;7,7 anos vs 42,2&#177;11,7 anos). </p>
    <p>Os participantes do G1 n&#227;o eram portadores de cardiopatia e tiveram ao ecocardiograma m&#233;dia de 49,6 mm de di&#226;metro diast&#243;lico final (DDF) e m&#233;dia de 30,8 mm de di&#226;metro sist&#243;lico final. A fra&#231;&#227;o de eje&#231;&#227;o dos participantes era normal e apresentou m&#233;dia de 67,2 %. Nenhum dos integrantes era portador de marcapasso, ou fazia uso de medica&#231;&#227;o. </p>
    <p>Do G2 a classe funcional (classifica&#231;&#227;o da NYHA), 8,3% eram da classe funcional I, 50% da classe funcional II, 8,3% da III e 33,3% da classe IV. </p>
    <p>As medica&#231;&#245;es mais utilizadas pelos participantes do G2 eram IECA (91,7%), diur&#233;ticos em geral (66,7%), espironolactona (50,0%), caverdilol (50,0%), digoxina (33,3%) e amiodarona (33,3%). Os pacientes geralmente estavam usando mais de uma medica&#231;&#227;o. </p>
    <p>Sete (58,3%) pacientes eram portadores de marcapasso definitivo. As principais altera&#231;&#245;es eletrocardiogr&#225;ficas encontradas nos 5 pacientes que n&#227;o tinham marcapasso foram BRD (40%), HBAE (60%), ESV (40%), e BRE (40%). </p>
    <p>Dos 12 pacientes do G2, apenas 2 tinham ecocardiograma normal. Na <xref ref-type="table" rid="tab01">tabela I</xref>, s&#227;o descritas a distribui&#231;&#227;o das altera&#231;&#245;es encontradas. </p>
    <table-wrap id="tab01">
      <graphic xlink:href="1678-4170-abc-84-02-0137-00008-gt01.jpg"/></table-wrap>
    <p>As altera&#231;&#245;es da contratilidade segmentar estiveram sempre correlacionadas aos defeitos de condu&#231;&#227;o intraventricular observados. N&#227;o foi registrada a presen&#231;a de trombos. </p>
    <p>Observou-se uma m&#233;dia de n&#237;veis de PNB mais elevada no G2. (G2=293,0&#177;460,2 pg/ml vs G1= 4,4&#177;4,4 pg/ml). Esta diferen&#231;a foi estatisticamente significante (P&lt; 0,001). </p>
    <p>N&#227;o houve diferen&#231;a estatisticamente significante entre os n&#237;veis de PNB em rela&#231;&#227;o ao sexo e &#224; idade, em ambos os grupos. </p>
    <p>A <xref ref-type="table" rid="tab02">tabela II</xref> correlaciona os n&#237;veis s&#233;ricos de PNB e a classe funcional segundo a classifica&#231;&#227;o da NYHA, demonstrando tend&#234;ncia de n&#237;veis crescentes de PNB com a piora da sintomatologia. </p>
    <table-wrap id="tab02">
      <graphic xlink:href="1678-4170-abc-84-02-0137-00008-gt02.jpg"/></table-wrap>
    <p>N&#227;o se observou diferen&#231;a estatisticamente significativa nos n&#237;veis de PNB entre o subgrupo que portava marcapasso (MP) definitivo: (217 pg/ml) e o de n&#227;o portadores de MP (49,8 pg/ml). (p=0,062). </p>
    <p>Mesmo n&#227;o sendo estatisticamente significativo observou-se correla&#231;&#227;o entre os n&#237;veis de PNB e o tamanho do cora&#231;&#227;o, observado ao estudo radiogr&#225;fico do t&#243;rax. </p>
    <p>N&#227;o houve diferen&#231;as significativas entre os portadores das diversas altera&#231;&#245;es eletrocardiogr&#225;ficas (BRD, HBAE, ESV e BRE) e os n&#237;veis s&#233;ricos de PNB. </p>
    <p>No G2, os pacientes com aumento de c&#226;maras card&#237;acas ao ecocardiograma tiveram valores de PNB m&#237;nimo de 3,6 pg/ml, m&#225;ximo de 1.300,0 pg/ml e m&#233;dio de 344,9 pg/ml. Enquanto que nos 2 com cora&#231;&#245;es de dimens&#245;es normais, variaram de 4,9 a 63,20 pg/ml, m&#233;dio de 34,05 pg/ml, n&#227;o sendo todavia, estatisticamente diferentes (p=0,41). </p>
    <p>A fun&#231;&#227;o ventricular sist&#243;lica tamb&#233;m esteve diretamente relacionada aos n&#237;veis de PNB. Observou-se uma tend&#234;ncia ao aumento dos n&#237;veis de PNB, com o maior comprometimento da fun&#231;&#227;o ventricular, embora o achado tenha sido marginalmente significante (p=0,06). </p>
    <p>Com rela&#231;&#227;o a fun&#231;&#227;o diast&#243;lica n&#227;o se observou, na amostra estudada, diferen&#231;a nos n&#237;veis de PNB e seu respectivo comprometimento da fun&#231;&#227;o (p=0,43). Os valores de PHB relacionados aos da fun&#231;&#227;o ventricular equerda, sist&#243;lica e diast&#243;lica, est&#227;o sumariados na <xref ref-type="table" rid="tab03">tabela III</xref>. </p>
    <table-wrap id="tab03">
      <graphic xlink:href="1678-4170-abc-84-02-0137-00008-gt03.jpg"/></table-wrap>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>Os pept&#237;deos natriur&#233;ticos t&#234;m sido utilizados cada vez mais como marcadores de morbimortalidade nas cardiopatias. Na doen&#231;a de Chagas, prevalente em popula&#231;&#245;es menos favorecidas economicamente, at&#233; hoje n&#227;o h&#225; registro de observa&#231;&#245;es com <italic>o Triage</italic><sup>&#174;</sup><italic> BNP test</italic>, comercialmente dispon&#237;vel para determina&#231;&#227;o sang&#252;&#237;nea do PNB. Os estudos existentes utilizaram outras t&#233;cnicas de determina&#231;&#227;o e contemplaram a forma congestiva, onde existe comprometimento card&#237;aco evidente. Na fase intermedi&#225;ria ou indeterminada, em que existe apenas sorologia positiva e nenhuma altera&#231;&#227;o cl&#237;nica, eletrocardiogr&#225;fica, radiol&#243;gica ou ecocardiogr&#225;fica, n&#227;o h&#225;, ainda, investiga&#231;&#227;o sobre a determina&#231;&#227;o do PNB por qualquer das t&#233;cnicas. </p>
    <p>O <italic>Triage</italic><sup>&#174;</sup><italic> BNP Test, Biosite</italic><sup>&#174;</sup>&#233; uma tecnologia j&#225; aprovada, pela sua efic&#225;cia e precis&#227;o em determinar os n&#237;veis s&#233;ricos do PNB<sup>6</sup> e o seu uso foi licenciado pela FDA americano. </p>
    <p>No presente estudo, os dois grupos investigados apresentaram diferen&#231;as estatisticamente significativas nos n&#237;veis de PNB (p&lt;0,01). Os chag&#225;sicos sem comprometimento card&#237;aco apresentaram n&#237;veis preconizados como normais pelo m&#233;todo, enquanto os chag&#225;sicos com comprometimento card&#237;aco apresentaram n&#237;veis s&#233;ricos diferentes, que aumentavam de acordo com a classe funcional e com as dimens&#245;es do cora&#231;&#227;o. </p>
    <p>O grupo 2 foi constitu&#237;do por 12 pacientes em graus diferentes de comprometimento card&#237;aco. Houve um n&#250;mero maior de portadores de classe funcional I e II, uma vez que 58,4% estavam situados na faixa dos pouco sintom&#225;ticos, supostamente com menores &#237;ndices de dilata&#231;&#227;o das c&#226;maras card&#237;acas e, provavelmente, menores n&#237;veis de PNB. Note-se que este pept&#237;deo tem como est&#237;mulo &#224; sua libera&#231;&#227;o a distens&#227;o das cavidades card&#237;acas. Caso o estudo tivesse envolvido apenas portadores de cardiopatia chag&#225;sica cr&#244;nica na forma congestiva, seriam observadas, muito provavelmente, diferen&#231;as maiores entre os dois grupos. Por outro lado, o fato de serem estudados pacientes com comprometimentos card&#237;acos diversos e em variados est&#225;gios da doen&#231;a, possibilitou inferir a import&#226;ncia do PNB, n&#227;o apenas nos quadros de insufici&#234;ncia card&#237;aca congestiva, como tamb&#233;m nos indiv&#237;duos sem sinais e/ou sintomas de disfun&#231;&#227;o ventricular esquerda. </p>
    <p>A classe funcional, segundo a classifica&#231;&#227;o da NYHA, esteve diretamente relacionada aos n&#237;veis s&#233;ricos do PNB, o que est&#225; de acordo, com a literatura, exceto em rela&#231;&#227;o &#224; classe funcional III que nesta amostra, n&#227;o evidenciou valores maiores do que a II. Conv&#233;m ressaltar que na classe III havia apenas um indiv&#237;duo, o que representa um vi&#233;s da amostra. Todavia, se forem agrupadas as classes III e IV constata-se que os n&#237;veis de PNB s&#227;o estatisticamente diferentes dos das classes I e II. </p>
    <p>O implante de marcapasso, mesmo traduzindo uma maior gravidade da doen&#231;a, independente da &#225;rea card&#237;aca ou dos volumes ventriculares, n&#227;o elevou significativamente os n&#237;veis de PNB. </p>
    <p>Altera&#231;&#245;es da contratilidade segmentar, presen&#231;a de aneurisma apical ou trombo intracavit&#225;rio, s&#227;o elementos freq&#252;entes nos eco-cardiogramas dos chag&#225;sicos cr&#244;nicos. O fato de n&#227;o serem observados no presente estudo, pode ser atribu&#237;do ao tamanho pequeno da amostra: 12 pacientes com comprometimento card&#237;aco, sendo 7 portadores de marcapasso card&#237;aco, condi&#231;&#227;o que dificulta a observa&#231;&#227;o das altera&#231;&#245;es de contratilidade. </p>
    <p>Os &#237;ndices de fra&#231;&#227;o de eje&#231;&#227;o do grupo 2 apresentaram uma m&#233;dia de 50,9%&#177;14,2), traduzindo que este grupo, em sua maioria, era formado por indiv&#237;duos com leve comprometimento da fun&#231;&#227;o sist&#243;lica ventricular esquerda. </p>
    <p>A fra&#231;&#227;o de eje&#231;&#227;o n&#227;o esteve diretamente relacionada aos n&#237;veis de PNB. Todavia, embora n&#227;o houvesse uma rela&#231;&#227;o linear, os indiv&#237;duos com comprometimento da fun&#231;&#227;o sist&#243;lica apresentaram n&#237;veis aumentados de PNB. Na presente amostra tamb&#233;m n&#227;o foi poss&#237;vel estabelecer correla&#231;&#227;o entre os n&#237;veis de PNB e disfun&#231;&#227;o diast&#243;lica. </p>
    <p>Considerando a rela&#231;&#227;o custo/benef&#237;cio n&#227;o parece poss&#237;vel no momento, preconizar o uso dessa tecnologia para programas nacionais de sa&#250;de p&#250;blica, uma vez que outras t&#233;cnicas diagn&#243;sticas, de menor custo, permanecem &#250;teis. </p>
    <p>&#201; interessante observar que, nos pacientes cr&#244;nicos com comprometimento card&#237;aco, mesmo sem que houvesse dilata&#231;&#227;o de c&#226;maras card&#237;acas, registrou-se diferen&#231;a estatisticamente significante dos n&#237;veis s&#233;ricos de PNB, em rela&#231;&#227;o aos pacientes que possu&#237;am somente sorologia positiva, o que faz crer que &#233; poss&#237;vel que o PNB preste-se para avaliar a gravidade da doen&#231;a de Chagas, n&#227;o apenas nos indiv&#237;duos congestos mas tamb&#233;m naqueles com as formas incipientes da doen&#231;a. </p>
    <p>&#201; necess&#225;rio que novas pesquisas, utilizando amostras populacionais maiores sejam realizadas, para que seja poss&#237;vel avaliar, com maior seguran&#231;a, a utilidade do PNB na estratifica&#231;&#227;o do risco dos portadores de cardiopatia chag&#225;sica cr&#244;nica, uma vez que a doen&#231;a apresenta graus variados de comprometimento<sup>7</sup>. A determina&#231;&#227;o s&#233;rica de PNB pode auxiliar no estabelecimento da estrat&#233;gia terap&#234;utica mais adequada, como ocorre na insufici&#234;ncia card&#237;aca de outras causas. A mensura&#231;&#227;o deste pept&#237;deo nos chag&#225;sicos cr&#244;nicos poder&#225; tamb&#233;m servir para o diagn&#243;stico diferencial da descompensa&#231;&#227;o card&#237;aca, j&#225; que outras causas podem cursar com sintomatologia id&#234;ntica, sem que alterem significativamente os n&#237;veis de PNB, como &#233; o caso da doen&#231;a pulmonar obstrutiva cr&#244;nica e outras s&#237;ndromes respirat&#243;rias. Intercorr&#234;ncias ou doen&#231;as associadas como anemias, infec&#231;&#245;es, principalmente respirat&#243;rias, que podem atingir o chag&#225;sico cr&#244;nico, poder&#227;o ter estratificada a sua participa&#231;&#227;o na descompensa&#231;&#227;o card&#237;aca pela determina&#231;&#227;o dos n&#237;veis de PNB. &#201; poss&#237;vel que a maior compreens&#227;o da fisiopatologia destes pept&#237;deos na doen&#231;a de Chagas venha a propiciar a sua aplica&#231;&#227;o terap&#234;utica.</p>
    <p>
      <fn id="end" fn-type="corresp">
        <label>
          <bold>Endere&#231;o para correspond&#234;ncia</bold>
        </label>
        <p> Edgar Guimar&#227;es Victor </p>
        <p> Av. Beira Mar, 138/101 - Piedade </p>
        <p> Cep 54160-230 - Jaboat&#227;o dos Guararapes - PE </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="edgardvictor@cardiol.br">edgardvictor@cardiol.br</email>
        </p>
      </fn>
    </p>
    <p>Recebido em 02/02/2004 </p>
    <p> Aceito em 07/04/2004</p>
  </body>
  <back>
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  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Measurement of human brain natriuretic peptide in patients with Chagas' disease</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>OBJECTIVE: To measure the serum levels of brain natriuretic peptide (BNP) in patients with chronic chagasic heart disease and in individuals with positive serology for Chagas' disease and no heart impairment, and to correlate the serum BNP levels with the degree of cardiac impairment, cardiac dimensions, presence of a pacemaker, and ejection fraction. METHODS: Serum BNP concentrations were determined by use of the Triage - BNP Test produced by BIOSITE. Serum BNP was assessed in 25 patients from the Chagas' disease outpatient clinic of the Hospital Universit&#225;rio Oswaldo Cruz, who were divided into 2 groups as follows: 1) G1 - comprising 13 assymptomatic patients with positive serology for Chagas' disease and no heart disease detectable on electrocardiography, chest X-ray, and echocardiography; and 2) G2 - comprising 12 patients with Chagas' disease and heart impairment. RESULTS: Significantly more elevated BNP levels were detected in the chagasic patients with cardiac impairment: (G1=4.4 &#177;4.4 pg/ml, G2=293.0&#177;460.2 pg/ml); (P&lt;0.01). In the 2 groups, the serum levels of BNP correlated neither with age nor with sex. The levels were directly proportional to functional class and cardiac area on chest X-ray. Although a trend towards an increment in systolic function impairment was observed, no linear correlation with the ejection fraction on echocardiography occurred. The presence of definitive pacemaker and electrocardiographic alterations did not change the serum BNP levels. CONCLUSION: Asymptomatic individuals with a positive serology for Chagas' disease and no evidence of ventricular dysfunction have serum BNP levels similar to those of the general population.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Chagas' disease</kwd>
        <kwd>natriuretic peptides</kwd>
        <kwd>cerebral natriuretic peptide</kwd>
        <kwd>congestive heart failure</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ORIGINAL ARTICLE</bold>
      </p>
      <p>Measurement of human brain natriuretic peptide in patients with Chagas' disease</p>
      <p>Railton Bezerra de Melo; Giordano Bruno de Oliveira Parente; Edgar Guimar&#227;es Victor</p>
      <p>Recife, PE - Brazil</p>
      <p>Universidade Federal de Pernambuco </p>
      <p>
        <xref ref-type="corresp" rid="end-body2">Correspondence</xref>
      </p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p><bold>OBJECTIVE: </bold> To measure the serum levels of brain natriuretic peptide (BNP) in patients with chronic chagasic heart disease and in individuals with positive serology for Chagas' disease and no heart impairment, and to correlate the serum BNP levels with the degree of cardiac impairment, cardiac dimensions, presence of a pacemaker, and ejection fraction.</p>
      <p><bold>METHODS: </bold> Serum BNP concentrations were determined by use of the Triage - BNP Test produced by BIOSITE. Serum BNP was assessed in 25 patients from the Chagas' disease outpatient clinic of the Hospital Universit&#225;rio Oswaldo Cruz, who were divided into 2 groups as follows: 1) G1 - comprising 13 assymptomatic patients with positive serology for Chagas' disease and no heart disease detectable on electrocardiography, chest X-ray, and echocardiography; and 2) G2 - comprising 12 patients with Chagas' disease and heart impairment.</p>
      <p><bold>RESULTS: </bold> Significantly more elevated BNP levels were detected in the chagasic patients with cardiac impairment: (G1=4.4 &#177;4.4 pg/ml, G2=293.0&#177;460.2 pg/ml); (P&lt;0.01). In the 2 groups, the serum levels of BNP correlated neither with age nor with sex. The levels were directly proportional to functional class and cardiac area on chest X-ray. Although a trend towards an increment in systolic function impairment was observed, no linear correlation with the ejection fraction on echocardiography occurred. The presence of definitive pacemaker and electrocardiographic alterations did not change the serum BNP levels.</p>
      <p><bold>CONCLUSION: </bold> Asymptomatic individuals with a positive serology for Chagas' disease and no evidence of ventricular dysfunction have serum BNP levels similar to those of the general population. </p>
      <p><bold>Key words: </bold>Chagas' disease, natriuretic peptides, cerebral natriuretic peptide, congestive heart failure</p>
      <p> Chagas' disease is the fourth major cause of impairment among transmissible diseases in Latin America, where 16 to 18 million people are estimated to be infected <sup>1</sup>. In Brazil, 6 to 8 million infected people exist <sup>2</sup>. Chagas' heart disease may manifest in several forms, and the individual may either be asymptomatic with no evidence of cardiac impairment, or have cardiomyopathy with heart failure and several cardiac arrhythmias. </p>
      <p>Patients with congestive heart failure have been demonstrated to have high serum levels of ANP and brain natriuretic peptide (BNP), and those levels correlate with the extension of ventricular dysfunction, being increased by 30 times in patients with advanced heart disease. High concentrations also predict short survival and correlate more closely with prognosis <sup>3-5</sup>. </p>
      <p>Due to the importance of BNP as a marker of severity and mortality in several diseases, mainly in heart diseases, measurement of its serum levels in Chagas' disease is justified. Alterations in BNP levels may be involved in the different clinical phases of the disease. This technique may support the formulation of more adequate therapeutic strategies according to the patient's biochemical profile. </p>
      <p>
        <bold>Methods</bold>
      </p>
      <p>The participants in the study originated from the Chagas' disease outpatient clinic of the Hospital Universit&#225;rio Oswaldo Cruz of the Universidade de Pernambuco. They were recruited through a letter. </p>
      <p>The population studied comprised 25 individuals divided into 2 groups as follows: 1) group 1 (G1) - comprising 13 individuals referred by a hemotherapy institution due to positive serology for Chagas' disease. The individuals had no cardiac impairment, verified through the lack of clinical symptomatology and no alteration suggestive of heart disease on electrocardiography, chest X-ray, and Doppler echocardiography; 2) group 2 (G2) - comprising 12 patients with the chronic cardiac form of Chagas' disease who were followed up at that outpatient clinic, seropositive for Chagas' disease, and who had cardiac impairment identified by the presence of symptomatology and alterations compatible with chagasic heart disease on electrocardiography, chest X-ray or Doppler echocardiography, or both. </p>
      <p>For serologic confirmation of Chagas' disease, indirect hemagglutination and indirect immunofluorescence were used in both groups. </p>
      <p>The exclusion criteria were as follows: presence of any other heart or systemic disease; use of noncardiologic medication that could significantly alter BNP levels; physiological states that could significantly change BNP levels, such as pregnancy, being less than 18 years old, and mental disability. </p>
      <p> After collecting the blood sample, transferring micropipettes available with the BNP kit were used, and their content was added to the Triage BNP Test Device at room temperature. </p>
      <p>The following variables were studied: age, sex, NYHA functional class of heart failure, medication use, presence of pacemaker, and electrocardiographic, echocardiographic and radiographic alterations. </p>
      <p>The echocardiographic parameters analyzed were as follows: the dimensions, thickness and volumes of the cardiac cavities; the characteristics of left ventricular regional and overall contratillity; and the flow waves on Doppler, from which the left ventricular diastolic function derived. If the systolic function (measured by Simpson method) was decreased, the impairment was classified as mild, moderate or severe. Structural alterations, mobility of the cardiac valves, and presence of intracavitary thrombi were assessed. </p>
      <p>As the samples studied had a markedly asymmetric distribution, the groups were compared by using the Kruskal-Wallis nonparametric test. </p>
      <p>The present study was approved by the Committee on Ethics of the HUOC-UPE, which follows the guidelines of the resolution 196/96 of the National Health Council. After being more carefully instructed about the research, all patients signed the written informed consent. </p>
      <p>
        <bold>Results</bold>
      </p>
      <p>The total population of the study comprised 25 patients divided into the 2 following groups: 1) G1 - comprising 13 individuals, 7 men (69.2%) and 6 women (30.8 %); and 2) G2 - comprising 12 individuals, half of them women, with a mean age greater than that in G1 (62.7&#177;7.7 anos vs 42.2&#177;11.7 anos). </p>
      <p>The G1 participants had no heart disease, and, on echocardiography, the mean end-diastolic and end-systolic diameters were 49.6 mm and 30.8 mm, respectively. The ejection fraction of the participants was normal, its mean being 67.2%. The participants used neither a pacemaker nor medication. </p>
      <p>The distribution of G2 patients according to NYHA functional classes was as follows: functional class I, 8.3%; functional class II, 50%; functional class III, 8.3%; and functional class IV, 33.3%. </p>
      <p>The most used medications by G2 patients were as follows: ACE inhibitors, 91.7%; diuretics, in general, 66.7%; spironolactone, 50.0%; carvedilol, 50.0%; digoxin, 33.3%; and amiodarone, 33.3%. The patients usually were on more than one medication. </p>
      <p>Seven (58.3%) patients had a definitive pacemaker. The major electrocardiographic alterations found in the 5 patients who had no pacemaker were as follows: right bundle-branch block, 40%; left anterior hemiblock, 60%; ESV, 40%; and left bundle-branch block, 40%. </p>
      <p>Of the 12 G2 patients, only 2 had a normal echocardiogram. <xref ref-type="table" rid="tab01-body2">Table I</xref> shows the distribution of the alterations found. </p>
      <table-wrap id="tab01-body2">
        <graphic xlink:href="1678-4170-abc-84-02-0137-00008-gt01-en.jpg"/></table-wrap>
      <p>The alterations in segmentary contractility always correlated with the defects of intraventricular conduction observed. No thrombi were observed. </p>
      <p>The mean BNP level was more elevated in G2 (G2=293.0&#177; 460.2 pg/ml vs G1=4.4&#177;4.4 pg/ml). This difference was statistically significant (P &lt; 0.001). </p>
      <p>No statistically significant difference was observed in BNP levels in regard to sex and age in both groups. </p>
      <p><xref ref-type="table" rid="tab02-body2">Table II</xref> correlates the serum levels of BNP and NYHA functional class classification, showing a trend towards an increase in BNP levels as symptomatology worsens. </p>
      <table-wrap id="tab02-body2">
        <graphic xlink:href="1678-4170-abc-84-02-0137-00008-gt02-en.jpg"/></table-wrap>
      <p>No statistically significant difference was observed in BNP levels between the individuals with a definitive pacemaker (PM, n=217) and those who had no PM (n=49.8; P=0.062). </p>
      <p>Although not statistically significant, a correlation between BNP levels and heart size on chest X-ray was observed. </p>
      <p>No significant differences were observed between the individuals with electrocardiographic alterations (right bundle-branch block, left anterior hemiblock, ESV, and left bundle-branch block) and the serum BNP levels. </p>
      <p>In G2, the patients with enlarged cardiac chambers on the echocardiogram had the following BNP values: minimum, 3.6 pg/mL; maximum, 1,300.0 pg/mL; and mean, 344.9 pg/mL. In the 2 patients whose hearts were of normal dimensions, those values ranged from 4.9 to 63.20 pg/mL, with a mean of 34.05; the difference, however, was not statistically significant (P=0.41). </p>
      <p>Left ventricular systolic function was also directly related to BNP levels. A trend towards an increase in BNP levels was observed, with a greater impairment in ventricular function, although the finding was marginally significant (P=0.06). </p>
      <p>In regard to diastolic function impairment, no difference in the respective BNP levels was observed in the sample studied (P=0.43). <xref ref-type="table" rid="tab03-body2">Table III</xref> shows the correlation of BNP values and left ventricular. </p>
      <table-wrap id="tab03-body2">
        <graphic xlink:href="1678-4170-abc-84-02-0137-00008-gt03-en.jpg"/></table-wrap>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>Natriuretic peptides have been increasingly used as markers of morbidity and mortality in heart diseases. In regard to Chagas' disease, prevalent in economically less favored populations, so far no study has been reported using the Triage BNP Test, commercially available for serum BNP measurement. The existing studies used other techniques for BNP measurement and assessed the congestive form of the disease, in which cardiac impairment is evident. In the intermediate or undetermined phase, which has only positive serology and no clinical, electrocardiographic, radiological, or echocardiographic alteration, no investigation exists about BNP measurement using any technique. </p>
      <p>The technology of the Triage BNP Test (Biosite, San Diego, CA) has already been approved, due to its efficacy and accuracy for determining the serum levels of BNP <sup>6</sup>, and the North American FDA has licensed its use. </p>
      <p>In the present study, the 2 groups investigated had statistically significant differences in BNP levels (P&lt;0.01). The chagasic patients with no cardiac impairment had BNP levels recommended as normal according to the method; however, the chagasic patients with cardiac impairment had different serum levels that increased according to functional class and cardiac dimensions. </p>
      <p>Group 2 comprised 12 patients with different degrees of cardiac impairment. Most patients were in functional classes I or II, because 58.4% had few symptoms, and, supposedly, had lower indices of heart chamber dilation and, probably, lower BNP levels. It is worth noting that distension of the cardiac cavities stimulates the release of that peptide. If the study had comprised only patients with the congestive form of chronic chagasic heart disease, greater differences might have been observed between the 2 groups. On the other hand, the fact that the study comprised patients with different degrees of cardiac involvement and in different stages of the disease allowed the inference of the importance of BNP not only in patients with congestive heart failure, but also in individuals without signs or symptoms, or both, of left ventricular dysfunction. </p>
      <p>The NYHA functional class was directly related to serum BNP levels, which is in accordance with the literature, except for functional class III, which did not show values greater than those in functional class II. It is worth noting that only one individual was in functional class III, which represents a bias in the sample. However, if functional classes III and IV are combined, the BNP levels are statistically different from those in functional classes I and II. </p>
      <p>Pacemaker implantation, even indicating a greater severity of the disease, regardless of the cardiac area and ventricular volumes, did not significantly increase BNP levels. </p>
      <p>Alterations in segmentary contractility, and presence of apical aneurysm or intracavitary thrombus are elements frequently found on echocardiograms of chronic chagasic patients. The fact that they were not observed in the present study may be attributed to the small size of the sample: 12 patients with cardiac impairment, 7 of whom had pacemakers, a condition that hinders the observation of the alterations in contractility. </p>
      <p>In group 2, the mean ejection fraction was 50.9% (SD=14.2), indicating that that group was mostly formed of individuals with a mild impairment in their left systolic ventricular function. </p>
      <p>Ejection fraction did not directly correlate with BNP levels. However, although no linear relation existed, the individuals with impairment in their systolic function had increased BNP levels. In the present sample, no correlation could be established between BNP levels and diastolic dysfunction. </p>
      <p>Considering the cost/benefit ratio, the use of this technology cannot be recommended for national programs of public health, because other less expensive diagnostic techniques remain useful. </p>
      <p>It is worth noting that in chronic patients with cardiac impairment, even without dilation in the cardiac chambers, a statistically significant difference in the serum levels of BNP was observed in comparison with patients who had only positive serology. This makes us believe that BNP may be useful for assessing the severity of Chagas' disease not only in congestive individuals but also in those with the incipient forms of the disease. </p>
      <p>New studies with larger population samples are required for more safely assessing the usefulness of BNP in risk stratification in patients with chronic chagasic heart disease, who have different degrees of impairment <sup>7</sup>. Serum measurement of BNP may help in establishing the most adequate therapeutic strategy, similarly to that which occurs in heart failure of other causes. Measurement of that peptide in chronic chagasic patients may also serve for the differential diagnosis of heart decompensation, as other causes may have an identical symptomatology without a significant change in BNP levels, such as chronic obstructive pulmonary disease and other respiratory syndromes. Complications or associated diseases, such as anemias and infections, mainly respiratory, which may affect the chronic chagasic patient, may have its participation in cardiac decompensation stratified by the determination of BNP levels. A larger understanding of the pathophysiology of those peptides in Chagas' disease may propitiate their therapeutic application.</p>
      <p>
        <bold>References</bold>
      </p>
      <p>
        <fn id="end-body2" fn-type="corresp">
          <label>
            <bold>Correspondence to</bold>
          </label>
          <p> Edgar Guimar&#227;es Victor</p>
          <p> Av. Beira Mar, 138/101</p>
          <p> Cep 54160-230 - Jaboat&#227;o dos Guararapes, PE, Brazil</p>
          <p> E-mail: </p>
          <p>
            <email xlink:href="edgardvictor@cardiol.br">edgardvictor@cardiol.br</email>
          </p>
        </fn>
      </p>
      <p>Received for publication: 02/02/2004</p>
      <p> Accepted for publication: 04/07/2004</p>
      <p> English version by Stela Maris Costalonga</p>
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  </sub-article>
</article>
