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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">6w7tpbVRPmdWqcGGT39CJQv</article-id>
      <article-id pub-id-type="other">00004</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2006000300004</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(06)08600304</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2006000300004</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Dosagem dos n&#237;veis de NT pro-BNP nas afec&#231;&#245;es peric&#225;rdicas e sua utilidade como m&#233;todo complementar de avalia&#231;&#227;o de restri&#231;&#227;o diast&#243;lica. Experi&#234;ncia inicial de 25 casos: 25 cases</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Fernandes</surname>
            <given-names>F&#225;bio</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Almeida</surname>
            <given-names>Izabel Jos&#233; de</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ramires</surname>
            <given-names>F&#233;lix J. A.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Buck</surname>
            <given-names>Paula C.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Salemi</surname>
            <given-names>Vera M. C.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ianni</surname>
            <given-names>B&#225;rbara M.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rabelo</surname>
            <given-names>Rog&#233;rio</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mady</surname>
            <given-names>Charles</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <institution content-type="orgname">Hospital das Cl&#237;nicas</institution>
        <institution content-type="orgdiv1">Instituto do Cora&#231;&#227;o </institution>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>03</month>
        <year>2006</year>
      </pub-date>
      <volume>86</volume>
      <issue>3</issue>
      <fpage>175</fpage>
      <lpage>180</lpage>
      <history>
        <date date-type="accepted">
          <day>30</day>
          <month>03</month>
          <year>2005</year>
        </date>
        <date date-type="received">
          <day>28</day>
          <month>10</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 se os n&#237;veis de NT pro-BNP encontram-se elevados em pacientes com afec&#231;&#245;es peric&#225;rdicas e avaliar a sua rela&#231;&#227;o com medidas ecocardiogr&#225;ficas de disfun&#231;&#227;o diast&#243;lica. M&#201;TODOS: Vinte e cinco pacientes foram divididos em dois grupos: 1) derrame peric&#225;rdico (DP), 15 pacientes; 2) pericardite constritiva (PC), 10 pacientes. Foi constitu&#237;do um grupo controle de 30 indiv&#237;duos sem doen&#231;a card&#237;aca. O grau de derrame peric&#225;rdico foi avaliado pelo ecocardiograma bidimensional e a restri&#231;&#227;o avaliada pelo Doppler puls&#225;til do fluxo mitral. O diagn&#243;stico de PC foi confirmado por meio da resson&#226;ncia magn&#233;tica. Os n&#237;veis de NT pro-BNP foram medidos por imunoensaio com detec&#231;&#227;o por eletroquimioluminesc&#234;ncia. RESULTADOS: Dos 15 pacientes com DP, 14 apresentavam DP importante e apenas 1, moderado. Log NT pro-BNP esteve aumentado no DP (p &lt;0,05), com m&#233;dia de log 2,31 pg/ml e PC (p &lt;0,05), com m&#233;dia de log 2,67 pg/ml, quando comparados ao grupo controle, m&#233;dia de log 1,32 pg/ml. N&#227;o houve diferen&#231;a entre DP e PC (p = 0,149). O log NT pro-BNP correlacionou-se com o pico de velocidade da onda E (r = 0,845; p = 0,001) e com a rela&#231;&#227;o E/A (r=0,717; p= 0,003). CONCLUS&#195;O: O NT pro-BNP encontra-se aumentado nas afec&#231;&#245;es peric&#225;rdicas e apresenta rela&#231;&#227;o com o grau de disfun&#231;&#227;o diast&#243;lica, podendo servir como m&#233;todo adicional na quantifica&#231;&#227;o de restri&#231;&#227;o.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Derrame peric&#225;rdico</kwd>
        <kwd>pericardite constritiva</kwd>
        <kwd>NT pro-BNP</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>30</day>
        <month>03</month>
        <year>2006</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>ARTIGO ORIGINAL</bold>
    </p>
    <p>Dosagem dos n&#237;veis de NT pro-BNP nas afec&#231;&#245;es peric&#225;rdicas e sua utilidade como m&#233;todo complementar de avalia&#231;&#227;o de restri&#231;&#227;o diast&#243;lica. Experi&#234;ncia inicial de 25 casos </p>
    <p>
      <bold>F&#225;bio Fernandes; Izabel Jos&#233; de Almeida; F&#233;lix J. A. Ramires; Paula C. Buck; Vera M. C. Salemi; B&#225;rbara M. Ianni; Rog&#233;rio Rabelo; Charles Mady</bold>
    </p>
    <p>Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas - 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>OBJETIVO: </bold>Determinar se os n&#237;veis de NT pro-BNP encontram-se elevados em pacientes com afec&#231;&#245;es peric&#225;rdicas e avaliar a sua rela&#231;&#227;o com medidas ecocardiogr&#225;ficas de disfun&#231;&#227;o diast&#243;lica. </p>
    <p><bold>M&#201;TODOS: </bold>Vinte e cinco pacientes foram divididos em dois grupos: 1) derrame peric&#225;rdico (DP), 15 pacientes; 2) pericardite constritiva (PC), 10 pacientes. Foi constitu&#237;do um grupo controle de 30 indiv&#237;duos sem doen&#231;a card&#237;aca. O grau de derrame peric&#225;rdico foi avaliado pelo ecocardiograma bidimensional e a restri&#231;&#227;o avaliada pelo Doppler puls&#225;til do fluxo mitral. O diagn&#243;stico de PC foi confirmado por meio da resson&#226;ncia magn&#233;tica. Os n&#237;veis de NT pro-BNP foram medidos por imunoensaio com detec&#231;&#227;o por eletroquimioluminesc&#234;ncia. </p>
    <p><bold>RESULTADOS: </bold>Dos 15 pacientes com DP, 14 apresentavam DP importante e apenas 1, moderado. Log NT pro-BNP esteve aumentado no DP (p &lt;0,05), com m&#233;dia de log 2,31 pg/ml e PC (p &lt;0,05), com m&#233;dia de log 2,67 pg/ml, quando comparados ao grupo controle, m&#233;dia de log 1,32 pg/ml. N&#227;o houve diferen&#231;a entre DP e PC (p = 0,149). O log NT pro-BNP correlacionou-se com o pico de velocidade da onda E (r = 0,845; p = 0,001) e com a rela&#231;&#227;o E/A (r=0,717; p= 0,003). </p>
    <p><bold>CONCLUS&#195;O: </bold>O NT pro-BNP encontra-se aumentado nas afec&#231;&#245;es peric&#225;rdicas e apresenta rela&#231;&#227;o com o grau de disfun&#231;&#227;o diast&#243;lica, podendo servir como m&#233;todo adicional na quantifica&#231;&#227;o de restri&#231;&#227;o. </p>
    <p><bold>Palavras-chave:</bold> Derrame peric&#225;rdico, pericardite constritiva, NT pro-BNP.</p>
    <p>As doen&#231;as peric&#225;rdicas apresentam v&#225;rias etiologias, levando a diferentes tipos de acometimentos morfol&#243;gicos. O exame f&#237;sico e os m&#233;todos complementares n&#227;o-invasivos s&#227;o &#250;teis no diagn&#243;stico de derrames e constri&#231;&#245;es peric&#225;rdicas. Entretanto, ainda existem dificuldades na quantifica&#231;&#227;o da restri&#231;&#227;o nestes pacientes. </p>
    <p>A decis&#227;o de se adotar uma t&#233;cnica invasiva &#233; influenciada pelo quadro cl&#237;nico do paciente. Quando este &#233; evidente, com presen&#231;a de hipotens&#227;o arterial, dispn&#233;ia e pulso paradoxal, n&#227;o existe controv&#233;rsia quanto ao procedimento. Por outro lado, o achado de derrame peric&#225;rdico importante e aus&#234;ncia de sintomatologia leva-nos a uma d&#250;vida quanto &#224; necessidade de interven&#231;&#227;o<sup>1</sup>.</p>
    <p>O NT pro-BNP &#233; descrito como sendo um marcador de disfun&#231;&#227;o sist&#243;lica e diast&#243;lica, sendo utilizado como m&#233;todo complementar na avalia&#231;&#227;o e acompanhamento de pacientes com insufici&#234;ncia card&#237;aca<sup>2</sup>.</p>
    <p>O objetivo deste estudo foi determinar os n&#237;veis s&#233;ricos de NT pro-BNP nos pacientes com derrame peric&#225;rdico e pericardite constritiva e avaliar sua rela&#231;&#227;o com as medidas de fun&#231;&#227;o diast&#243;lica, obtidas pelo ecocardiograma.</p>
    <p>
      <bold>M&#201;TODOS</bold>
    </p>
    <p>Foram avaliados, de forma prospectiva e consecutiva, 25 pacientes sintom&#225;ticos, no per&#237;odo de 2003 a 2004. Os pacientes foram divididos em grupo derrame peric&#225;rdico (DP), 15 pacientes, 10 mulheres, 3 da ra&#231;a negra, com idade entre 21 e 76 anos (m&#233;dia 54&#177;15), e 10 pacientes com pericardite constritiva (PC), 3 mulheres, 2 da ra&#231;a negra, com idade entre 16 e 71 anos (m&#233;dia 32&#177;17). Foi constitu&#237;do um grupo controle de 30 indiv&#237;duos sem doen&#231;a card&#237;aca, sendo 15 mulheres, 2 da ra&#231;a negra, com idade entre 37 e 68 anos (m&#233;dia 47&#177;12).</p>
    <p>Ap&#243;s a avalia&#231;&#227;o cl&#237;nica inicial, o tipo de acometimento foi caracterizado pelo ecocardiograma e pela resson&#226;ncia magn&#233;tica, nos casos de espessamento peric&#225;rdico. </p>
    <p>Foram considerados como crit&#233;rios de exclus&#227;o: creatinina s&#233;rica &gt; 1,4 mg/dl, disfun&#231;&#227;o ventricular esquerda (fra&#231;&#227;o de eje&#231;&#227;o &lt; 55%, avaliada pelo ecocardiograma pelo m&#233;todo Teichholz), fibrila&#231;&#227;o atrial, gravidez e lacta&#231;&#227;o.</p>
    <p>O estudo ecocardiogr&#225;fico foi realizado com os pacientes em dec&#250;bito lateral esquerdo e dorsal, com o aparelho <italic>Acuson</italic> (Sequ&#243;ia 512, Montain View, CA), equipado com transdutor multifreq&#252;encial de 2,5 - 4,0 MHz. Foram realizados estudos ecocardiogr&#225;ficos completos, sendo obtidas pelo menos tr&#234;s medidas de cada vari&#225;vel e, a seguir, calculou-se a m&#233;dia de cada valor obtido.</p>
    <p>As medidas, em modo-M, foram feitas de acordo com as recomenda&#231;&#245;es da Sociedade Americana de Ecocardiografia<sup>3</sup>. A massa ventricular esquerda foi calculada por meio da f&#243;rmula modificada de Devereux, corrigida pela &#225;rea de superf&#237;cie corporal e expressa tamb&#233;m como &#237;ndice de massa<sup>4</sup>. A fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo foi determinada pelo m&#233;todo de Teichholz<sup>5</sup>. Derrame peric&#225;rdico importante foi definido pela presen&#231;a de derrame peric&#225;rdico posterior e anterior maior que 20 mm e moderado, entre 10 e 20 mm<sup>6</sup>.</p>
    <p>O fluxo mitral foi obtido pelo Doppler puls&#225;til em corte apical 4 c&#226;maras, com a amostra de volume posicionada nas bordas dos folhetos valvares, com redu&#231;&#227;o do ganho e filtro para obter melhor defini&#231;&#227;o do fluxo. Foram medidos o pico de velocidade das ondas E e A, rela&#231;&#227;o E/A<sup>7</sup>.</p>
    <p>Para a an&#225;lise da varia&#231;&#227;o respirat&#243;ria da velocidade de fluxo mitral, foi obtida a m&#233;dia da onda E de 3 ciclos card&#237;acos na inspira&#231;&#227;o e de outros 3 ciclos na expira&#231;&#227;o. Assim, dessas m&#233;dias, foi calculada a varia&#231;&#227;o percentual, sendo considerado valor de refer&#234;ncia uma varia&#231;&#227;o <underline>&gt;</underline> 25%<sup>8,9</sup>.</p>
    <p>O diagn&#243;stico de pericardite constritiva foi confirmado pelos achados da resson&#226;ncia magn&#233;tica, pela presen&#231;a de espessamento peric&#225;rdico acima de 4 mm. </p>
    <p>A determina&#231;&#227;o do NT pro-BNP foi realizada com a coleta de sangue perif&#233;rico em veia do antebra&#231;o em tubo seco, mantido em gelo e centrifugado sob refrigera&#231;&#227;o por 10 minutos a 3.000 rpm. Separado o soro usado na determina&#231;&#227;o do NT pro-BNP, os n&#237;veis foram medidos por imunoensaio, com detec&#231;&#227;o por eletroquimioluminesc&#234;ncia. </p>
    <p>Para an&#225;lise estat&#237;stica, foram utilizados o teste ANOVA e o teste Tukey HSD para avaliar as diferen&#231;as do log NT pro-BNP entre os grupos. O coeficiente de correla&#231;&#227;o de Spearman foi utilizado para analisar a rela&#231;&#227;o entre o log NT pro-BNP e os par&#226;metros ecocardiogr&#225;ficos (pico de velocidade da onda E, A e rela&#231;&#227;o E/A).</p>
    <p>
      <bold>RESULTADOS</bold>
    </p>
    <p>Quatorze pacientes apresentavam derrame peric&#225;rdico importante e apenas um, moderado. Tr&#234;s pacientes apresentavam sinais ecocardiogr&#225;ficos de tamponamento card&#237;aco. O diagn&#243;stico etiol&#243;gico foi de tuberculose (2), adenocarcinoma pulmonar (1), hipotiroidismo (1), doen&#231;a reumatol&#243;gica (3), artrite reumat&#243;ide (2), esclerodermia - s&#237;ndrome CREST (1) e idiop&#225;tico (10). Em apenas quatro pacientes n&#227;o foi realizada a pericardiocentese, sendo introduzido tratamento espec&#237;fico para a doen&#231;a de base (horm&#244;nios tireoidianos e antiinflamat&#243;rios). </p>
    <p>Na pericardite constritiva, o diagn&#243;stico foi secund&#225;rio a tuberculose em 2 pacientes, sendo nos outros, idiop&#225;tico. Os sintomas relatados foram: dispn&#233;ia aos esfor&#231;os (8 pacientes), aumento de volume abdominal com ascite (5 pacientes), edema de membros inferiores (6 pacientes). Todos os pacientes com PC foram operados, com exce&#231;&#227;o de um, que evoluiu para &#243;bito enquanto aguardava compensa&#231;&#227;o cl&#237;nica para cirurgia. Esse era o paciente que apresentava maiores n&#237;veis de NT pro-BNP do estudo.</p>
    <p>O resultados ecocardiogr&#225;ficos dos pacientes com derrame peric&#225;rdico e pericardite constritiva est&#227;o descritos na <xref ref-type="table" rid="tab01">tabela 1</xref>.</p>
    <table-wrap id="tab01">
      <graphic xlink:href="1678-4170-abc-86-03-0175-00004-gt01.jpg"/></table-wrap>
    <p>O log NT pro-BNP esteve estatisticamente aumentado (p &lt; 0,05) no DP, com m&#233;dia de log 2,31 pg/ml (IC 95%: 2,00-2,61 log pg/ml) e PC, com m&#233;dia de log 2,67 pg/ml (IC 95%: 2,29-3,05 log pg/ml), quando comparados a um grupo controle, com m&#233;dia de log 1,32 pg/ml (IC 95%: 1,18-1,47 log pg/ml). N&#227;o houve diferen&#231;a estatisticamente significante entre DP e PC (p=0,149) (<xref ref-type="fig" rid="fig01">figs. 1</xref> e <xref ref-type="fig" rid="fig02">2</xref>). Log NT pro-BNP correlacionou-se com par&#226;metros ecocardiogr&#225;ficos E/A (r = 0,717; p = 0,003) e pico de velocidade da onda E (r = 0,845; p = 0,001) (<xref ref-type="fig" rid="fig03">figs. 3</xref> e <xref ref-type="fig" rid="fig04">4</xref>).</p>
    <fig id="fig01">
      <graphic xlink:href="1678-4170-abc-86-03-0175-00004-gf01.jpg"/></fig>
    <fig id="fig02">
      <graphic xlink:href="1678-4170-abc-86-03-0175-00004-gf02.jpg"/></fig>
    <fig id="fig03">
      <graphic xlink:href="1678-4170-abc-86-03-0175-00004-gf03.jpg"/></fig>
    <fig id="fig04">
      <graphic xlink:href="1678-4170-abc-86-03-0175-00004-gf04.jpg"/></fig>
    <p>
      <bold>DISCUSS&#195;O</bold>
    </p>
    <p>Neste estudo, foi demonstrado que pacientes com comprometimento peric&#225;rdico e fun&#231;&#227;o ventricular preservada apresentam n&#237;veis elevados de NT pro-BNP. Este achado abre perspectivas para utiliza&#231;&#227;o do m&#233;todo como exame complementar no diagn&#243;stico de restri&#231;&#227;o em pacientes com derrames e constri&#231;&#245;es peric&#225;rdicas. </p>
    <p>O achado de derrame peric&#225;rdico importante ou de espessamento peric&#225;rdico, ao ecocardiograma, em pacientes sem sinais e sintomas cl&#237;nicos de restri&#231;&#227;o, deixa d&#250;vida quanto &#224; realiza&#231;&#227;o ou n&#227;o de pericardiocentese ou de outro procedimento cir&#250;rgico. </p>
    <p>A indica&#231;&#227;o de interven&#231;&#227;o peric&#225;rdica &#233; controversa, sendo que alguns autores sugerem a realiza&#231;&#227;o de pericardiocentese de rotina com finalidade diagn&#243;stica, a despeito da presen&#231;a de tamponamento<sup>10</sup>. Para este prop&#243;sito, a bi&#243;psia peric&#225;rdica por Marfan apresenta baixa sensibilidade, (cerca de 10,5%), devendo a decis&#227;o ser individualizada<sup>11</sup>. Por outro lado, nem sempre existe correla&#231;&#227;o entre os achados cl&#237;nicos e ecocardiogr&#225;ficos no diagn&#243;stico de tamponamento em pacientes com derrame peric&#225;rdico moderado a importante. Merc&#233; e cols.<sup>6 </sup>encontraram colapsos de c&#226;maras direita em 53% dos pacientes com efus&#245;es importantes. Cerca de 89% dos pacientes com sintomas cl&#237;nicos de tamponamento demonstravam colapso de pelo menos uma c&#226;mara. Todavia, em 33% dos pacientes que n&#227;o apresentavam sintomas de tamponamento existia colapso de pelo menos uma c&#226;mara.</p>
    <p>O grau da volemia, press&#245;es intracard&#237;acas, espessamento e rigidez das paredes card&#237;acas s&#227;o fatores que, ao ecocardiograma, influenciam parcialmente a presen&#231;a de colapso das c&#226;maras<sup>12</sup>. Sagrist&#224;-Sauleda e cols.<sup>13</sup>, avaliando pacientes com derrame peric&#225;rdico importante por um longo per&#237;odo, conclu&#237;ram que efus&#227;o &#233; bem tolerada na maioria dos pacientes, por&#233;m a presen&#231;a de tamponamento ocorreu inesperadamente. </p>
    <p>Neste estudo, a avalia&#231;&#227;o da fun&#231;&#227;o diast&#243;lica do VE foi feita por meio do Doppler puls&#225;til do fluxo mitral. Entretanto, este fluxo oscila em forma de U ou de par&#225;bola. Assim, indiv&#237;duos normais apresentam a rela&#231;&#227;o E/A entre 1 e 2. &#192; medida que ocorre a disfun&#231;&#227;o diast&#243;lica, esta rela&#231;&#227;o fica &lt; 1 (padr&#227;o altera&#231;&#227;o do relaxamento), onde apenas o relaxamento est&#225; alterado. Quando, al&#233;m do relaxamento lentificado, a complac&#234;ncia ou distensibilidade ventricular fica comprometida, observa-se padr&#227;o pseudonormal, caracterizado por E/A entre 1 e 2. Na presen&#231;a de relaxamento lentificado, complac&#234;ncia reduzida e aumento importante da press&#227;o atrial esquerda, o fluxo de enchimento ventricular torna-se restritivo, caracterizado por E/A &gt;2. A limita&#231;&#227;o da an&#225;lise da fun&#231;&#227;o diast&#243;lica apenas pelo Doppler puls&#225;til do fluxo mitral &#233; que, por meio deste m&#233;todo, n&#227;o se pode diferenciar o padr&#227;o de enchimento ventricular normal do pseudonormal, sendo necess&#225;ria a utiliza&#231;&#227;o de outros m&#233;todos, como o fluxo de veias pulmonares ou o Doppler tecidual. Assim, a excelente correla&#231;&#227;o entre os &#237;ndices de fun&#231;&#227;o diast&#243;lica (E e E/A) e o NT pro-BNP, observada neste estudo, ocorreu devido ao fato de ser extremamente improv&#225;vel termos algum paciente com o padr&#227;o de enchimento ventricular normal. Desta forma, considerando apenas os padr&#245;es altera&#231;&#227;o de relaxamento, pseudormal e restritivo, que oscilam de forma linear, encontramos excelente correla&#231;&#227;o com o NT pro-BNP. </p>
    <p>M&#233;rce e cols.<sup>6</sup> descreveram sensibilidade e especificidade de 75% e 91%, respectivamente, da an&#225;lise do fluxo venoso em pacientes com sintomas cl&#237;nicos de tamponamento. Desta forma, a utiliza&#231;&#227;o de outros m&#233;todos complementares diagn&#243;sticos, tais como o NT pro-BNP, poderia auxiliar na escolha do melhor momento da interven&#231;&#227;o.</p>
    <p>Na literatura, existem poucos estudos que avaliaram a presen&#231;a de fatores natriur&#233;ticos nas afec&#231;&#245;es peric&#225;rdicas, a maioria, utilizando o fator natriur&#233;tico atrial. Nestes estudos, h&#225; aumento do fator natriur&#233;tico atrial ap&#243;s a corre&#231;&#227;o cir&#250;rgica do tamponamento e da pericardite constritiva. A explica&#231;&#227;o para tal fato seria de que as afe&#231;&#245;es peric&#225;rdicas ocasionariam restri&#231;&#227;o da distensibilidade atrial, limitando a secre&#231;&#227;o do fator natriur&#233;tico atrial e reduzindo seus efeitos diur&#233;ticos e natriur&#233;ticos<sup>14,15</sup>. Com rela&#231;&#227;o ao BNP, apenas um estudo avaliou seus n&#237;veis em pacientes com tamponamento antes e ap&#243;s 30 minutos da pericardiocentese. Os resultados demonstraram que o BNP estava significantemente aumentado em rela&#231;&#227;o ao grupo controle, n&#227;o havendo diferen&#231;as ap&#243;s o procedimento terap&#234;utico<sup>16</sup>. </p>
    <p>Acreditamos que a disfun&#231;&#227;o diast&#243;lica secund&#225;ria ao derrame e &#224; constri&#231;&#227;o peric&#225;rdica estaria relacionada com a eleva&#231;&#227;o dos n&#237;veis s&#233;ricos de NT pro-BNP. Estudos experimentais demonstram que mesmo colapsos regionais est&#227;o associados &#224; redu&#231;&#227;o do d&#233;bito card&#237;aco e que este achado ecocardiogr&#225;fico usualmente ocorre antes do desenvolvimento de hipotens&#227;o e do pulso paradoxal<sup>17</sup>. </p>
    <p>Kaszaki e cols.<sup>18 </sup>demonstraram que com a redu&#231;&#227;o do d&#233;bito card&#237;aco no tamponamento peric&#225;rdico experimental existia libera&#231;&#227;o de subst&#226;ncia vasoativas. Dentre as subst&#226;ncias vasoconstritoras, destacou-se a libera&#231;&#227;o de vasopressina, epinefrina, norepinefrina e renina. Al&#233;m disso, com o efeito de atenuar e contra-regular a excessiva libera&#231;&#227;o de subst&#226;ncias vasoconstritoras, houve tamb&#233;m libera&#231;&#227;o de uma subst&#226;ncia vasodilatadora, a histamina. Talvez esta seria uma outra poss&#237;vel explica&#231;&#227;o para o aumento dos n&#237;veis dos horm&#244;nios natriur&#233;ticos, que s&#227;o subst&#226;ncias sabidamente vasodilatadoras.</p>
    <p>Na constri&#231;&#227;o peric&#225;rdica, a indica&#231;&#227;o cir&#250;rgica cl&#225;ssica ocorre nos casos em que h&#225; insufici&#234;ncia card&#237;aca cl&#237;nica. Nesta condi&#231;&#227;o, a interven&#231;&#227;o n&#227;o deve ser adiada, pois, pacientes em classe funcional avan&#231;ada (IV da NYHA) apresentam maior mortalidade (30 - 40% x 6 - 19%) e menor benef&#237;cio. A melhora da sintomatologia e a normaliza&#231;&#227;o das press&#245;es card&#237;acas podem ocorrer em alguns meses ap&#243;s pericardiectomia<sup>19</sup>. J&#225; nos casos de pacientes em classe funcional I, sem sinais cl&#237;nicos de insufici&#234;ncia card&#237;aca, a pericardiectomia n&#227;o deve ser realizada<sup>12</sup>. </p>
    <p>As formas subcl&#237;nicas de constri&#231;&#227;o incluem pacientes que, ap&#243;s um ou v&#225;rios surtos de inflama&#231;&#227;o peric&#225;rdica, evoluem com espessamento peric&#225;rdico. Este grupo mereceu pouca aten&#231;&#227;o at&#233; o momento, sendo a forma menos estudada desta mol&#233;stia. &#201; aquela na qual os pacientes s&#227;o assintom&#225;ticos, apresentando altera&#231;&#245;es ecocardiogr&#225;ficas e fun&#231;&#227;o sist&#243;lica em repouso normal. O fato de serem assintom&#225;ticos gera dificuldade diagn&#243;stica e conseq&#252;ente subvaloriza&#231;&#227;o do problema. Como uma parte deles evolui para constri&#231;&#227;o, com todas as suas conseq&#252;&#234;ncias, &#233; importante termos profundo conhecimento sobre essa fase evolutiva da doen&#231;a. Se tivermos possibilidade de acompanhar esses indiv&#237;duos com dosagens seriadas de marcadores de disfun&#231;&#227;o diast&#243;lica, poderemos modificar as curvas de sobrevida, com indica&#231;&#227;o precoce de pericardiectomia. Nosso estudo demonstrou que, em pacientes sintom&#225;ticos com constri&#231;&#227;o peric&#225;rdica, h&#225; aumento dos n&#237;veis de NT pro-BNP. O NT pro-BNP poderia ser mais um m&#233;todo complementar no seguimento dos casos iniciais de espessamento peric&#225;rdico, quando o paciente ainda n&#227;o apresenta sinais e sintomas de insufici&#234;ncia card&#237;aca. </p>
    <p>Por outro lado, o NT pro-BNP poderia tamb&#233;m ser utilizado como fator progn&#243;stico. O paciente do grupo com pericardite constritiva que evoluiu para &#243;bito era aquele que tamb&#233;m apresentava maiores n&#237;veis de NT pro-BNP. </p>
    <p>Este estudo demonstra a experi&#234;ncia inicial com o uso do NT pro-BNP para diagn&#243;stico complementar nas afec&#231;&#245;es peric&#225;rdicas. Entretanto, acreditamos que apenas um estudo com um n&#250;mero maior de pacientes poderia responder a algumas quest&#245;es do m&#233;todo com rela&#231;&#227;o &#224; sensibilidade, especificidade, valores preditivos positivo e negativo, bem como, marcador progn&#243;stico nas restri&#231;&#245;es peric&#225;rdicas. </p>
    <p>
      <bold>Agradecimentos</bold>
    </p>
    <p>A M&#225;rcia Moreira Holcman, pelo aux&#237;lio na an&#225;lise estat&#237;stica.</p>
    <p>
      <fn id="end" fn-type="corresp">
        <label>
          <bold>Correspond&#234;ncia</bold>
        </label>
        <p> Fabio Fernandes </p>
        <p> Av. Dr. En&#233;as de Carvalho Aguiar, 44 </p>
        <p> 05403-000 &#150; S&#227;o Paulo, SP </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="car_fabio@incor.usp.br">car_fabio@incor.usp.br</email>
        </p>
      </fn>
    </p>
    <p>Recebido em 28/10/04 </p>
    <p> Aceito em 30/03/05</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">NT Pro-BNP levels in pericardial diseases and how they are used as complementary evaluation method of diastolic restriction. Inititial experience</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>OBJECTIVE: To determine whether NT pro-BNP levels are high in patients reporting pericardial diseases, as well as to investigate how they relate to diastolic dysfunction echocardiographic measures. METHODS: Twenty-five patients were split into two groups: 1) pericardial effusion (PE): 15 patients; 2) constrictive pericaditis (CP): 10 patients. A control group was made up with 30 individuals reporting no heart disease. Pericadial effusion was evaluated by bidimensional echocardiogram, with restriction evaluated by pulsed Doppler of mitral flow. CP diagnosis was confirmed by MRI. NT pro-BNP levels were measured by immunoassay and detected by electrochemiluminescence. RESULTS: From the 15 PD patients, 14 reported relevant PD, and only 1, moderate PD. Log NT pro-BNP was shown to be higher in PD (p &lt;0.05), with log mean of 2.31 pg/ml and CP (p &lt;0.05), with log mean of 2.67 pg/ml, when compared to control group, log mean of 1.32 pg/ml. No difference was reported between PD and CP (p = 0.149). The NT pro-BNP log showed to be correlated to peak velocity of the E wave (r = 0.845; p = 0.001) and with E/A (r=0.717; p= 0.003). CONCLUSION: NT pro-BNP is shown to have increased in pericardial diseases, and is associated to diastolic dysfunction. It may serve as an additional method in quantifying restriction.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Pericardial effusion</kwd>
        <kwd>constrictive pericaditis</kwd>
        <kwd>NT pro-BNP</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ORIGINAL ARTICLE</bold>
      </p>
      <p> NT pro-BNP levels in pericardial diseases and how they are used as complementary evaluation method of diastolic restriction. Inititial experience: 25 cases </p>
      <p>
        <bold>F&#225;bio Fernandes; Izabel Jos&#233; de Almeida; F&#233;lix J. A. Ramires; Paula C. Buck; Vera M. C. Salemi; B&#225;rbara M. Ianni; Rog&#233;rio Rabelo; Charles Mady</bold>
      </p>
      <p>Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas - 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>OBJECTIVE: </bold>To determine whether NT pro-BNP levels are high in patients reporting pericardial diseases, as well as to investigate how they relate to diastolic dysfunction echocardiographic measures.</p>
      <p><bold>METHODS: </bold>Twenty-five patients were split into two groups: 1) pericardial effusion (PE): 15 patients; 2) constrictive pericaditis (CP): 10 patients. A control group was made up with 30 individuals reporting no heart disease. Pericadial effusion was evaluated by bidimensional echocardiogram, with restriction evaluated by pulsed Doppler of mitral flow. CP diagnosis was confirmed by MRI. NT pro-BNP levels were measured by immunoassay and detected by electrochemiluminescence.</p>
      <p><bold>RESULTS: </bold>From the 15 PD patients, 14 reported relevant PD, and only 1, moderate PD. Log NT pro-BNP was shown to be higher in PD (p &lt;0.05), with log mean of 2.31 pg/ml and CP (p &lt;0.05), with log mean of 2.67 pg/ml, when compared to control group, log mean of 1.32 pg/ml. No difference was reported between PD and CP (p = 0.149). The NT pro-BNP log showed to be correlated to peak velocity of the E wave (r = 0.845; p = 0.001) and with E/A (r=0.717; p= 0.003).</p>
      <p><bold>CONCLUSION: </bold>NT pro-BNP is shown to have increased in pericardial diseases, and is associated to diastolic dysfunction. It may serve as an additional method in quantifying restriction.</p>
      <p><bold>Key words: </bold>Pericardial effusion, constrictive pericaditis, NT pro-BNP.</p>
      <p>Pericardial diseases are presented through different etiologies, leading to different morphologic conditions. Physical examination and non-invasive complementary methods are useful in diagnosing pericardial effusion and constriction. However, difficulties are still being faced for restriction quantification in those patients. </p>
      <p>The decision to adopt an invasive technique is affected by patient&#146;s condition. When the condition is obvious, with records of hypotension, dyspnea, and paradoxal pulse, no controversy is posed regarding procedures. However, if findings include significant pericardial effusion and no symptoms, the need for intervention is questioned<sup>1</sup>.</p>
      <p>NT pro-BNP is described as a systolic and diastolic dysfunction marker. It is used as a complementary method for the evaluation and the monitoring of heart failure patients<sup>2</sup>.</p>
      <p>The purpose of the present study was to determine NT pro-BNP serum level in patients reporting pericardial effusion and constrictive pericarditis, as well as evaluating their association with echocardiographic diastolic function measures.</p>
      <p>
        <bold>METHODS</bold>
      </p>
      <p>Twenty-five patients were submitted to prospective and consecutive evaluation between 2003-2004. Patients were split into the pericardial effusion (PE) group - 15 patients, 10 females, being 3 Black women, age range 21-76 years old (mean 54&#177;15); and 10 patients reporting constrictive pericarditis (CP), 3 females, being 2 Black women, age range 16-71 years old (mean 32&#177;17). A control group was made up with 30 individuals reporting no heart diseases: 15 females, being 2 Black women, age range 37-68 years old (mean 47&#177;12).</p>
      <p>After initial clinical evaluation, condition was characterized by echocardiogram and MRI for those cases reporting pericardial thickening. </p>
      <p>The following exclusion criteria were used: serum creatinine &gt; 1.4 mg/dl; left ventricular dysfunction (ejection fraction &lt; 55%, as assessed by echocardiogram, Teichholz method); atrial fibrillation; pregnancy; and lactation.</p>
      <p>The echocardiographic study was carried out with patients in left lateral and dorsal decubitus, using <italic>Acuson</italic> (Sequoia 512, Montain View, CA), equipped with a 2.5 &#150; 4.0 MHz multifrequency probe. Full echocardiographic studies were carried out, with at least three measures for each variable, after which means were calculated for each value obtained.</p>
      <p>M-mode measures were taken in compliance with the American Society of Echocardiography<sup>3</sup>. Left ventricular mass was calculated by Devereux-modified formula, corrected by body surface area, and also expressed as mass index<sup>4</sup>. Left ventricle ejection fraction was obtained through Teichholz<sup>5 </sup>method. Significant previous pericardial effusion was defined as larger than 20 mm posterior pericardial effusion; moderate was considered to be between 10 and 20 mm<sup>6</sup>.</p>
      <p>Mitral flow was obtained by apical 4-chamber view pulsed Doppler, with volume sample placed on valvar leaflets ridges, with gain reduction and filter for better definition of flow. E and A waves velocity peak as well as E/A ratio were measured<sup>7</sup>.</p>
      <p>For the analysis of respiratory variation of mitral flow velocity, E wave mean was obtained from 3 heart cycles in inspiration and 3 cycles in expiration. Then, based on those means, percentual variation was calculated. Reference variation value: <underline>&gt;</underline> 25%<sup>8,9</sup>.</p>
      <p>Constrictive pericarditis dignosis was confirmed by MRI findings: pericardial thickening above 4 mm. </p>
      <p>NT pro-BNP was determined by the collection of peripheral blood from the forearm into a dry tube, kept in ice and centrifuged at 10 minutes to 3,000 rpm under refrigeration. After serum used to determine NT pro-BNP was separated, levels were measured through immunoassay and detected by electrochemiluminescence. </p>
      <p>For the purpose of statistical analysis, ANOVA and Tukey HSD tests were used to investigate log NT pro-BNP differences between groups. Spearman correlation coeficient was used for the analysis of the association between log NT pro-BNP and echocardiographic parameters (E and A waves velocity peak, and E/A ratio). </p>
      <p>
        <bold>RESULTS</bold>
      </p>
      <p>Fourteen patients reported significant pericardial effusion; only one of them reported moderate effusion. Three patients presented echocardiographic signs of cardiac tamponade. Etiologic diagnosis was: tuberculosis (2), pulmonary adenocarcinoma (1), hypothyrodism (1), rheumatologic condition (3), rheumatoid arthritis (2), sclerodermy - CREST syndrome (1) and idiopathy (10). Pericardiocentesis was not carried out in four patients only. Specific treatment was introduced for base disease (thyroid and anti-inflamatory hormones). </p>
      <p>For constrictive pericarditis, diagnosis was secondary to tuberculosis in 2 patients; in all others, it was idiopathic. Symptoms reported included: dyspnea under effort (8 patients); increased abdominal volume with ascites (5 patients); edema in lower limbs (6 patients). All CP patients underwent surgery, except for one, whose death occurred while awaiting clinical compensation before surgery - the very patient who reported the highest NT pro-BNP levels in the study.</p>
      <p>Echocardiographic results of patients with pericar-dial effusion and constrictive pericarditis are described in <xref ref-type="table" rid="tab01-body2">Table 1</xref>.</p>
      <table-wrap id="tab01-body2">
        <graphic xlink:href="1678-4170-abc-86-03-0175-00004-gt01-en.jpg"/></table-wrap>
      <p>Log NT pro-BNP was shown to be statistically increased (p &lt;0.05) in PE, with log mean of 2.31 pg/ml (95% CI): 2.00-2.61 log pg/ml), and CP (p &lt;0.05), with log mean of 2.67 pg/ml (CI 95%: 2.29-3.05 log pg/ml), when compared to control group, log mean of 1.32 pg/ml (CI 95%: 1.18-1.47 log pg/ml). No statistically significant difference was reported between PE and CP (p=0.149) (<xref ref-type="fig" rid="fig01-body2">Figs. 1</xref> and <xref ref-type="fig" rid="fig02-body2">2</xref>). Log NT pro-BNP showed to be correlated to echocardiographic parameters E/A (r = 0.717; p = 0,003) an E wave peak velocity (r = 0.845; p= 0.001). (<xref ref-type="fig" rid="fig03-body2">Figs. 3</xref> and <xref ref-type="fig" rid="fig04-body2">4</xref>).</p>
      <fig id="fig01-body2">
        <graphic xlink:href="1678-4170-abc-86-03-0175-00004-gf01-en.jpg"/></fig>
      <fig id="fig02-body2">
        <graphic xlink:href="1678-4170-abc-86-03-0175-00004-gf02-en.jpg"/></fig>
      <fig id="fig03-body2">
        <graphic xlink:href="1678-4170-abc-86-03-0175-00004-gf03-en.jpg"/></fig>
      <fig id="fig04-body2">
        <graphic xlink:href="1678-4170-abc-86-03-0175-00004-gf04-en.jpg"/></fig>
      <p>
        <bold>DISCUSSION</bold>
      </p>
      <p>The study showed that patients reporting pericardial impairment and preserved ventricular function presented high levels of NT pro-BNP. Such finding opens the perspective for the use of the method as complementary exam for the diagnosis of restriction in patients with pericardial effusions and constrictions. </p>
      <p> The echocardiographic finding of significant pericardial effusion in patients who present no signs or clinical symptoms of restriction makes pericardiocentesis, or any other surgical procedure, questionable. </p>
      <p>The indication for pericardial intervention is controversial. Some authors suggest routine pericardiocentesis should be carried out for diagnosis purposes, despite tamponade<sup>10</sup>. To such purpose, pericardial biopsy by Marfan reports low sensitivity &#150; approximately 10.5%. Decision is to be made on case by case basis<sup>11</sup>. On the other hand, not always can one find correlation between clinical findings and echocardiographic findings when diagnosing tamponade pericardial effusion in patients reporting moderate to significant pericardial effusion. Merc&#233; and collaborators<sup>6 </sup>found left chamber collapses in 53% of patients reporting significant effusion. Approximately 89% of patients presenting tamponade clinical symptoms reported collapse in at least one chamber. However, 33% of patients that did not present tamponade symptoms reported collapse in at least one chamber.</p>
      <p>Level of volemia, intracardiac pressures, thickening, and cardiac walls stiffness are echocardiographic factors that partially influence the presence of a collapse in the chambers<sup>12</sup>. Sagrist&#224;-Sauleda and collaborators<sup>13</sup>, while on long-term evaluation of patients with pericardial effusion, concluded that effusion is well tolerated by most patients; however, tamponade occurred unexpectedly. </p>
      <p>In the present study, the investigation of LV diastolic function was carried out by pulsed Doppler of mitral flow. That flow oscilates, though, in a U shape or a parabola shape. So, normal individuals present E/A ratio between 1 and 2. As diastolic dysfunction occurs, it is shown to be &lt; 1 (pattern change for relaxation), when only relaxation is changed. When, in addition to slow relaxation, ventricular compliance or distensibility is compromised, a pseudonormal pattern can be observed, characterized by E/A between 1 and 2. Under slow relaxation, reduced compliance and significant increase of left atrial pressure, ventricular filling flow becomes restrictive, and is characterized by E/A &gt;2. The limitation posed to the analysis of diastolic function by pulsed Doppler of mitral flow only is that the method does not allow normal ventricular filling to be differentiated from pseudonormal filling, and other methods have to be put to use, such as pulmonary veins flow or tissue pulsed Doppler. Therefore, the excellent correlation between diastolic function ratio (E and E/A) and NT pro-BNP, as observed in the present study, resulted from the extremely improbable scenario of our counting on a patient reporting normal ventricular filling pattern. Therefore, considering relaxation, pseudonormal, and restrictive changes only, which oscilate linearly, excellent correlation with NT pro-BNP could be found. </p>
      <p>M&#233;rce and collaborators <sup>6</sup> have decribed sensitivity and specificity at 75% and 91%, respectively, for the venous flow in patients with tamponade clinical symptoms. Therefore, resorting to other complementary methods for diagnosis &#150; such as NT pro-BNP &#150; could help in choosing the best moment for intervention.</p>
      <p>Literature makes available few studies investigating the presence of natriuretic factors in pericardial diseases; most of them focus atrial natriuretic factor. Those studies report increase in atrial natriuretic factor after surgical correction of tamponade and of constrictive pericarditis. That could be explained by the fact that pericardial diseases supposedly cause atrial distensibility restriction, thus limiting atrial natriuretic factor secretion and reducing its diuretic and natriuretic effects<sup>14,15</sup>. In regard to BNP, only one study investigated those levels in patients with tamponade prior to and 30 minutes after pericardiocentesis. Results show that BNP was significantly increased as compared to control group. No differences were reported after therapeutic procedure<sup>16</sup>. </p>
      <p>The authors believe that diastolic dysfunction secondary to effusion and to pericardial constriction might be associated to NT pro-BNP serum level increase. Experimental studies have shown that even regional collapses are associated to cardiac debit, and that such echocardiographic finding usually occurs before the development of hypotension and paradoxical pulse<sup>17</sup>. </p>
      <p>Kaszaki and collaborators<sup>18 </sup>have demonstrated that cardiac debit reduction in experimental pericardial tamponade was associated to the release of vasoactive substances. Among the vasoconstrictive substances, vasopresine, epinephrine, and renin stand out. Additionally, to atennuate and counter-regulate excessive release of vasoconstricting substances, the release of a vasodilating substance &#150; histamine &#150; also occurred. That might also explain the increase of natriuretic hormone levels &#150; substances known to be vasodilating.</p>
      <p>In pericardial constriction, classic surgery is indicated for cases involving clinical heart failure. For such condition, intervention must not be postponed, since patients under advanced functional class (IV in NYHA) report higher mortality rate (30 - 40% x 6 - 19%) and lower benefits. Improvement of symptoms and normalization of cardiac pressures may occur within a few months after pericardiectomy<sup>19</sup>. As for patients in functional class I with no clinical signs of heart failure, pericardiectomy is not to be carried out<sup>12</sup>. </p>
      <p>Subclinical forms of constriction include patients that develop pericardial thickening after one or many outbreaks of pericardial inflammation. That group has deserved little attention up to this point in time; and this is the least studied aspect of the condition. Patients are asymptomatic, report echocardiographic alterations, and systolic function at normal rest position. By being asymptomatic, patients&#146; diagnosis is made more difficult, which results in underestimating the condition. As some patients develop into constriction, with all its consequences, it is important for physicians to be deeply aware of such stage in the course of the condition. If those individuals can be monitored with serial doses of diastolic dysfunction markers, survival curves will be changed, with early indication for pericardiectomy. Our study has demonstrated that pericardial constriction patients who are symptomatic report increase in NT pro-BNP levels. NT pro-BNP might be one more complementary method for the follow-up of early cases of pericardial thickening when patients do not yet present signs or symptoms of heart failure. </p>
      <p>On the other hand, NT pro-BNP might also be used as a prognostic factor. The patient in the constrictive pericarditis group whose condition developed into death was the same who reported the highest levels of NT pro-BNP. </p>
      <p>The present study demonstrates initial experiences with the use of NT pro-BNP as complementary diagnosis for pericardial diseases. However, the authors believe that only a study including a wider number of patients could answer some of the questions posed to the method regarding sensitivity, specificity, positive and negative predictive values, as well as prognostic markers for pericardial restrictions.</p>
      <p>
        <bold>Acknowledgments</bold>
      </p>
      <p>M&#225;rcia Moreira Holcman, for help and support in statistical analysis.</p>
      <p>
        <bold>REFERENCES</bold>
      </p>
      <p>
        <fn id="end-body2" fn-type="corresp">
          <label>
            <bold>Mailing Address:</bold>
          </label>
          <p> Fabio Fernandes</p>
          <p> Av. Dr. En&#233;as de Carvalho Aguiar, 44</p>
          <p> 05403-000 &#150; S&#227;o Paulo, SP - Brazil</p>
          <p> E-mail: </p>
          <p>
            <email xlink:href="car_fabio.incor.usp.br">car_fabio.incor.usp.br</email>
          </p>
        </fn>
      </p>
      <p>Received on 10/28/04</p>
      <p> Accepted on 03/30/05</p>
    </body>
  </sub-article>
</article>
