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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">nLndtGvGTwYnTjwnHLSg5Rp</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2013000100011</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(13)10000100011</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2012005000115</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo Original</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Dispers&#227;o da onda P e &#237;ndice de volume do &#225;trio esquerdo como preditores na insufici&#234;ncia card&#237;aca</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Silva</surname>
            <given-names>Rose Mary Ferreira Lisboa da</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Kazzaz</surname>
            <given-names>Nadya Mendes</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Torres</surname>
            <given-names>Ros&#225;lia Morais</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Moreira</surname>
            <given-names>Maria da Consola&#231;&#227;o Vieira</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="city">Belo Horizonte</named-content>
          <named-content content-type="state">Minas Gerais</named-content>
        </addr-line>
        <institution content-type="orgname">Universidade Federal de Minas Gerais</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina </institution>
        <country country="BR">Brazil</country>
      </aff>
      <aff id="aff02">
        <addr-line>
          <named-content content-type="city">Belo Horizonte</named-content>
          <named-content content-type="state"/>
        </addr-line>
        <institution content-type="orgname">Cl&#237;nica ECOGRAF</institution>
        <institution content-type="orgdiv1">N&#250;cleo de Diagn&#243;stico N&#227;o Invasivo </institution>
        <country country="BR">Brazil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>01</month>
        <year>2013</year>
      </pub-date>
      <volume>100</volume>
      <issue>1</issue>
      <fpage>67</fpage>
      <lpage>74</lpage>
      <history>
        <date date-type="received">
          <day>25</day>
          <month>05</month>
          <year>2012</year>
        </date>
        <date date-type="accepted">
          <day>15</day>
          <month>08</month>
          <year>2012</year>
        </date>
        <date date-type="rev-recd">
          <day>15</day>
          <month>08</month>
          <year>2012</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/" xml:lang="en">
          <license-p>This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.</license-p>
        </license>
      </permissions>
      <abstract>
        <p>FUNDAMENTO: Estudos demonstram que a dispers&#227;o da onda P (DP) e o &#237;ndice de volume do &#225;trio esquerdo (Aesc) s&#227;o preditores de eventos cardiovasculares (EC). OBJETIVO: Verificar o valor progn&#243;stico da dispers&#227;o da onda P e do Aesc para a ocorr&#234;ncia de EC em pacientes com insufici&#234;ncia card&#237;aca. M&#201;TODOS: Estudo longitudinal e prospectivo com 78 pacientes consecutivos com idade m&#233;dia de 47,2 anos, sendo 52 homens, est&#225;veis com insufici&#234;ncia card&#237;aca, submetidos &#224; avalia&#231;&#227;o cl&#237;nica, aos exames de eletrocardiograma e ao ecocardiograma, com seguimento de 26,5 meses. RESULTADOS: As m&#233;dias das vari&#225;veis foram: 50 ms DP e 35,5 ml/m&#178; Aesc. Considerando-se DP &gt; 40 ms e como refer&#234;ncia Aesc &gt; 28 ml/m&#178;, o valor preditivo positivo da DP foi de 87,5% e o negativo de 76,9%. Durante o seguimento, 21 pacientes apresentaram EC. Houve associa&#231;&#227;o entre as medidas do &#225;trio esquerdo, os volumes do ventr&#237;culo esquerdo e a fra&#231;&#227;o de eje&#231;&#227;o e EC. N&#227;o houve associa&#231;&#227;o entre a DP e EC. Pela an&#225;lise multivariada, o &#225;trio esquerdo e o Aesc foram preditores de eventos (p = 0,00 e 0,02). Pela curva de opera&#231;&#227;o caracter&#237;stica para a vari&#225;vel est&#225;vel EC, foram obtidas as &#225;reas de 0,80 e 0,69 para Aesc (p = 0,00) e Aesc &gt; 28 ml/m&#178; (p = 0,01). As curvas de sobrevida (Kaplan-Meier) livre daqueles eventos para Aesc &gt; 28 ml/m&#178; e para a etiologia chag&#225;sica demonstraram raz&#227;o de chance de 14,4 (p = 0,00) e de 3,2 (p = 0,03). N&#227;o houve diferen&#231;a de evolu&#231;&#227;o entre pacientes com insufici&#234;ncia card&#237;aca isqu&#234;mica e n&#227;o isqu&#234;mica. CONCLUS&#195;O: DP n&#227;o esteve correlacionada a EC. Aesc foi um preditor independente de EC e os chag&#225;sicos apresentaram pior evolu&#231;&#227;o.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>insufici&#234;ncia card&#237;aca</kwd>
        <kwd>onda p</kwd>
        <kwd>&#225;trios do cora&#231;&#227;o</kwd>
        <kwd>eletrocardiografia</kwd>
        <kwd>fibrila&#231;&#227;o atrial</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>11</day>
        <month>12</month>
        <year>2012</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>Dispers&#227;o da onda P e &#237;ndice de volume do &#225;trio esquerdo como preditores na insufici&#234;ncia card&#237;aca</bold>
    </p>
    <p>
      <bold>Rose Mary Ferreira Lisboa da Silva<sup>I</sup>; Nadya Mendes Kazzaz<sup>I, II</sup>; Ros&#225;lia Morais Torres<sup>I</sup>; Maria da Consola&#231;&#227;o Vieira Moreira<sup>I</sup></bold>
    </p>
    <p><sup>I</sup>Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil </p>
    <p><sup>II</sup>Cl&#237;nica ECOGRAF N&#250;cleo de Diagn&#243;stico N&#227;o Invasivo, Belo Horizonte, MG, Brasil</p>
    <p>
      <xref ref-type="corresp" rid="end">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>FUNDAMENTO:</bold> Estudos demonstram que a dispers&#227;o da onda P (DP) e o &#237;ndice de volume do &#225;trio esquerdo (Aesc) s&#227;o preditores de eventos cardiovasculares (EC). </p>
    <p><bold>OBJETIVO:</bold> Verificar o valor progn&#243;stico da dispers&#227;o da onda P e do Aesc para a ocorr&#234;ncia de EC em pacientes com insufici&#234;ncia card&#237;aca. </p>
    <p><bold>M&#201;TODOS: </bold>Estudo longitudinal e prospectivo com 78 pacientes consecutivos com idade m&#233;dia de 47,2 anos, sendo 52 homens, est&#225;veis com insufici&#234;ncia card&#237;aca, submetidos &#224; avalia&#231;&#227;o cl&#237;nica, aos exames de eletrocardiograma e ao ecocardiograma, com seguimento de 26,5 meses. </p>
    <p><bold>RESULTADOS:</bold> As m&#233;dias das vari&#225;veis foram: 50 ms DP e 35,5 ml/m<sup>2</sup> Aesc. Considerando-se DP <underline>&gt;</underline> 40 ms e como refer&#234;ncia Aesc <underline>&gt;</underline> 28 ml/m<sup>2</sup>, o valor preditivo positivo da DP foi de 87,5% e o negativo de 76,9%. Durante o seguimento, 21 pacientes apresentaram EC. Houve associa&#231;&#227;o entre as medidas do &#225;trio esquerdo, os volumes do ventr&#237;culo esquerdo e a fra&#231;&#227;o de eje&#231;&#227;o e EC. N&#227;o houve associa&#231;&#227;o entre a DP e EC. Pela an&#225;lise multivariada, o &#225;trio esquerdo e o Aesc foram preditores de eventos (p = 0,00 e 0,02). Pela curva de opera&#231;&#227;o caracter&#237;stica para a vari&#225;vel est&#225;vel EC, foram obtidas as &#225;reas de 0,80 e 0,69 para Aesc (p = 0,00) e Aesc <underline>&gt;</underline> 28 ml/m<sup>2</sup> (p = 0,01). As curvas de sobrevida (Kaplan-Meier) livre daqueles eventos para Aesc <underline>&gt;</underline> 28 ml/m<sup>2</sup> e para a etiologia chag&#225;sica demonstraram raz&#227;o de chance de 14,4 (p = 0,00) e de 3,2 (p = 0,03). N&#227;o houve diferen&#231;a de evolu&#231;&#227;o entre pacientes com insufici&#234;ncia card&#237;aca isqu&#234;mica e n&#227;o isqu&#234;mica. </p>
    <p><bold>CONCLUS&#195;O:</bold> DP n&#227;o esteve correlacionada a EC. Aesc foi um preditor independente de EC e os chag&#225;sicos apresentaram pior evolu&#231;&#227;o. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0)</p>
    <p><bold>Palavras-chave:</bold> insufici&#234;ncia card&#237;aca, onda p, &#225;trios do cora&#231;&#227;o, eletrocardiografia, fibrila&#231;&#227;o atrial.</p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p>A insufici&#234;ncia card&#237;aca (IC) representa um grave problema de sa&#250;de p&#250;blica e &#233; considerada uma pandemia do s&#233;culo XXI. Apresenta um aumento de sua preval&#234;ncia, com alta morbidade - 83% dos pacientes apresentando pelo menos uma interna&#231;&#227;o e 43% com pelo menos quatro interna&#231;&#245;es ap&#243;s seu diagn&#243;stico. A despeito dos avan&#231;os no tratamento e da melhora da sobrevida nas &#250;ltimas d&#233;cadas, as taxas anuais de mortalidade por insufici&#234;ncia card&#237;aca ainda s&#227;o altas, atingindo a propor&#231;&#227;o de todas as mortes de 40,5% nos homens e 59,5% nas mulheres, considerando-se todas as idades<sup>1-3</sup>. Assim, torna-se importante a estratifica&#231;&#227;o de risco dos pacientes est&#225;veis para predizer os eventos relacionados a esse quadro com o objetivo de uma abordagem mais racional. H&#225; estudos que demonstraram correla&#231;&#227;o entre as medidas da onda P, obtida por meio do eletrocardiograma convencional e/ou do de alta resolu&#231;&#227;o, e a ocorr&#234;ncia ou recorr&#234;ncia de fibrila&#231;&#227;o atrial (ap&#243;s cardiovers&#227;o el&#233;trica ou abla&#231;&#227;o por radiofrequ&#234;ncia)<sup>4-7</sup>, de arritmias atriais na s&#237;ndrome de Brugada<sup>8</sup> e ap&#243;s transplante card&#237;aco<sup>9</sup>, de hipertrofia e disfun&#231;&#227;o diast&#243;lica esquerda em pacientes hipertensos<sup>10</sup>, de IC<sup>11,12</sup> e de melhora da fra&#231;&#227;o de eje&#231;&#227;o ap&#243;s a terapia de ressincroniza&#231;&#227;o card&#237;aca<sup>13</sup>. Outros estudos demonstraram que o aumento do &#225;trio esquerdo, determinado principalmente pelo &#237;ndice de volume do &#225;trio esquerdo, &#233; um preditor de eventos cardiovasculares, como mortalidade, IC, interna&#231;&#227;o, necessidade de transplante card&#237;aco, maior incid&#234;ncia de acidente vascular encef&#225;lico e de fibrila&#231;&#227;o atrial, infarto agudo do mioc&#225;rdio e cirurgia de revasculariza&#231;&#227;o cir&#250;rgica<sup>14-17</sup>. No quadro de IC, os estudos progn&#243;sticos sobre as medidas da onda P em conjunto com as do &#225;trio esquerdo ainda s&#227;o escassos<sup>11,18</sup>, motivando o presente trabalho. Os principais objetivos deste trabalho s&#227;o correlacionar as medidas da onda P com o volume do &#225;trio esquerdo e seu &#237;ndice e verificar o valor progn&#243;stico destas medidas e outras vari&#225;veis em pacientes est&#225;veis com IC.</p>
    <p>
      <bold>M&#233;todos</bold>
    </p>
    <p>Trata-se de um estudo observacional, longitudinal e prospectivo. A popula&#231;&#227;o foi constitu&#237;da por 78 pacientes consecutivos, est&#225;veis, com IC independente da etiologia, em ritmo atrial sinusal, de ambos os sexos, com idade superior a 18 anos, que aceitaram participar do estudo. Tanto o projeto de pesquisa quanto o termo de consentimento livre e esclarecido (TCLE) foram aprovados pelo Comit&#234; de &#201;tica e Pesquisa da Universidade Federal de Minas Gerais (UFMG) (parecer n&#250;mero 270/06). Ap&#243;s o aceite e assinatura do TCLE, os pacientes foram submetidos &#224; avalia&#231;&#227;o cl&#237;nica e &#224; realiza&#231;&#227;o do eletrocardiograma (ECG) convencional de 12 deriva&#231;&#245;es de superf&#237;cie, ao eletrocardiograma de alta resolu&#231;&#227;o (ECGAR) e ao ecocardiograma transtor&#225;cico. Foram exclu&#237;dos pacientes com valvopatia, gestantes, pacientes com cardiopatia cong&#234;nita, aqueles j&#225; submetidos a transplante card&#237;aco e os portadores de doen&#231;a considerada terminal.</p>
    <p>O ECG de 12 deriva&#231;&#245;es foi realizado no eletrocardi&#243;grafo a velocidade de 50 mm/s e voltagem de 20 mm/mV para permitir a medida da dura&#231;&#227;o da onda P nas 12 deriva&#231;&#245;es e de sua dispers&#227;o (DP), definida pela diferen&#231;a entre seu valor m&#225;ximo e m&#237;nimo. O in&#237;cio da onda P foi definido na jun&#231;&#227;o entre a linha isoel&#233;trica e o in&#237;cio da deflex&#227;o ascendente e, o final, como o ponto entre o t&#233;rmino entre a deflex&#227;o e a linha isoel&#233;trica<sup>18</sup>. Ap&#243;s o registro, as medidas foram realizadas por dois observadores habilitados e independentes, antes da execu&#231;&#227;o do ecocardiograma e sem conhecimento das condi&#231;&#245;es cl&#237;nicas dos pacientes para se analisar a variabilidade interobservador.</p>
    <p>Foi realizada a obten&#231;&#227;o de um sinal eletrocardiogr&#225;fico pr&#243;-mediado, amplificado e filtrado, obtido pelas deriva&#231;&#245;es ortogonais X, Y e Z (ECGAR), com um ru&#237;do final &lt; 0,5 &#181;V e um n&#250;mero de batimentos ect&#243;picos inferior a 1% do total de batimentos. O registro foi captado durante um monitoramento de 16 minutos, utilizando um multicardi&#243;grafo digital, com os pacientes na posi&#231;&#227;o supina, em uma sala com isolamento de ru&#237;dos. A avalia&#231;&#227;o do sinal foi feita ap&#243;s edi&#231;&#227;o manual rigorosa dos registros. A dura&#231;&#227;o da onda P foi mensurada manualmente, do in&#237;cio ao fim do sinal, o qual apresentava uma amplitude de pelo menos duas vezes &#224; do ru&#237;do<sup>19</sup>.</p>
    <p>Os pacientes foram submetidos tamb&#233;m ao estudo ecocardiogr&#225;fico feito por dois observadores no mesmo momento. O volume do &#225;trio esquerdo foi obtido por interm&#233;dio do software do equipamento, utilizando as medidas do &#225;trio nos eixos cefalocaudal, laterolateral e obl&#237;quo. Foi utilizado para valor de corte do &#237;ndice de volume do &#225;trio esquerdo (Aesc - volume do &#225;trio esquerdo/superf&#237;cie corp&#243;rea) o valor de 28 ml/m<sup>2</sup> e 32 ml/m<sup>2</sup>, conforme a literatura de refer&#234;ncia<sup>14,20</sup>.</p>
    <p>O tempo m&#233;dio de seguimento foi de 26,5 &#177; 8,0 meses. As intercorr&#234;ncias cl&#237;nicas foram registradas, bem como as eventuais interna&#231;&#245;es hospitalares.</p>
    <p>
      <bold>An&#225;lise estat&#237;stica </bold>
    </p>
    <p>Para a an&#225;lise dos dados, foi utilizado o programa SPSS (<italic>Statistical Package for Social Science</italic>) vers&#227;o 14.0. Os resultados foram expressos em n&#250;meros e propor&#231;&#227;o, para vari&#225;veis discretas, e em medidas de tend&#234;ncia central e de dispers&#227;o, para as vari&#225;veis cont&#237;nuas. Os testes de Mann-Whitney, de Kurskall-Wallis e o teste do qui-quadrado ou de Fisher foram utilizados, quando apropriados, para comparar as diferen&#231;as entre as vari&#225;veis cont&#237;nuas e discretas, respectivamente. A correla&#231;&#227;o entre as vari&#225;veis foi feita pelo o coeficiente de Pearson. Para se analisar a variabilidade interobservador foi utilizado o teste de concord&#226;ncia de Kappa. A curva de opera&#231;&#227;o caracter&#237;stica foi utilizada para determinar a sensibilidade e especificidade para a DP e a Aesc. Foi utilizada a an&#225;lise de regress&#227;o log&#237;stica pelo m&#233;todo <italic>Stepwise</italic>, sendo a vari&#225;vel dependente a ocorr&#234;ncia de eventos cardiovasculares, considerando-se as vari&#225;veis com p <underline>&lt;</underline> 0,10 na an&#225;lise univariada. Foi realizada a an&#225;lise de sobrevida pela curva de Kaplan Meier, considerando-se a medida Aesc <underline>&gt;</underline> 28 ml/m<sup>2 </sup>e <underline>&gt;</underline> 32 ml/m<sup>2 </sup>e a etiologia da IC. Ficou estabelecido em 0,05 o n&#237;vel de rejei&#231;&#227;o da hip&#243;tese de nulidade.</p>
    <p>
      <bold>Resultados</bold>
    </p>
    <p>A casu&#237;stica foi composta por 78 pacientes, sendo 52 (66,6%) do sexo masculino e 26 (33,3%) do sexo feminino. A idade m&#233;dia foi de 47,2 &#177; 13,2 anos, variando de 19 a 71 anos. Os demais dados cl&#237;nicos est&#227;o dispostos na <xref ref-type="table" rid="aop312tab1">Tabela 1</xref>. Quanto &#224; etiologia da miocardiopatia, 23 pacientes apresentavam etiologia idiop&#225;tica, 17 chag&#225;sica, 15 isqu&#234;mica, em nove pacientes a etiologia foi hipertensiva, em seis alco&#243;lica e em cinco a etiologia foi periparto, e dois apresentaram miocardiopatia dilatada por causa de miocardite. Em rela&#231;&#227;o aos h&#225;bitos de vida, foi detectado tabagismo em 29 pacientes (37,2%) e etilismo em 21 pacientes (26,6%). Quanto &#224;s comorbidades, dezenove pacientes apresentavam hipertens&#227;o arterial sist&#234;mica; 16, diabetes<italic> mellitus</italic>; oito, hipotireoidismo e quatro apresentavam insufici&#234;ncia renal cr&#244;nica. Em rela&#231;&#227;o ao tratamento farmacol&#243;gico, 41 pacientes estavam em uso de inibidor de enzima de angiotensina, 24 de bloqueador do receptor da angiotensina, 59 em uso de furosemida, 53 de espironolactona, 10 de tiaz&#237;dico, 50 de carvedilol, tr&#234;s de metoprolol, 47 de digoxina, 10 de &#225;cido acetilsalic&#237;lico, 11 de estatina e 15 de dicumar&#237;nico.</p>
    <p content-type="asset">
      <table-wrap id="aop312tab1">
        <graphic xlink:href="1678-4170-abc-100-01-0067-00115-gt01.jpg"/></table-wrap>
    </p>
    <p>Ao ECG as m&#233;dias das medidas obtidas foram: dura&#231;&#227;o da onda P na deriva&#231;&#227;o D2 120,0 &#177; 14,6 ms; DP 50 &#177; 14,6 ms; dura&#231;&#227;o da onda P ao ECGAR 114,0 &#177; 20,8 ms (m&#233;dio de ru&#237;do de 0,3 &#177; 0,1 microvolt e n&#250;mero de ciclos captados de 975,6 &#177; 208,0). A variabilidade interobservador em rela&#231;&#227;o &#224;s medidas da onda P foi feita por meio do teste de concord&#226;ncia Kappa, sendo os valores de 0,69 para DP e de 0,86 para a dura&#231;&#227;o da onda P pelo ECGAR. Foi considerada a concord&#226;ncia entre os dois observadores a diferen&#231;a <underline>&lt;</underline> 10 ms, para medida da onda P por meio do ECG convencional, e <underline>&lt;</underline> 5 ms, pelo ECGAR.</p>
    <p>Ao ecocardiograma, as m&#233;dias mensuradas est&#227;o dispostas na <xref ref-type="table" rid="aop312tab2">Tabela 2</xref>.</p>
    <p content-type="asset">
      <table-wrap id="aop312tab2">
        <graphic xlink:href="1678-4170-abc-100-01-0067-00115-gt02.jpg"/></table-wrap>
    </p>
    <p>
      <bold>Associa&#231;&#227;o e correla&#231;&#227;o entre vari&#225;veis </bold>
    </p>
    <p>Aplicando-se o teste de Kruskal-Wallis para a an&#225;lise das vari&#225;veis entre os pacientes, segundo as etiologias chag&#225;sica, isqu&#234;mica e outras, foi obtido o valor-p de 0,015 para idade (47,1, 56,2 e 44,6 anos, respectivamente). N&#227;o houve diferen&#231;a significante em rela&#231;&#227;o &#224;s demais vari&#225;veis, sejam cl&#237;nicas, eletrocardiogr&#225;ficas ou ecocardiogr&#225;ficas. O sexo n&#227;o influenciou na etiologia da insufici&#234;ncia card&#237;aca (&#224; exce&#231;&#227;o da periparto).</p>
    <p>Os coeficientes de Pearson entre a DP e as vari&#225;veis ecocardiogr&#225;ficas, como di&#226;metro do &#225;trio esquerdo (AE), seu volume (VAE) e Aesc, e di&#226;metros diast&#243;lico e sist&#243;lico do ventr&#237;culo esquerdo, demonstraram valor-p de 0,00 para cada (r = 0,47, 0,42, 0,37, 0,46, 0,40, respectivamente). N&#227;o houve correla&#231;&#227;o entre a DP e a fra&#231;&#227;o de eje&#231;&#227;o (FE), seja pelo m&#233;todo Teichholz (p = 0,054) ou pelo m&#233;todo Simpson (p = 0,153). Em rela&#231;&#227;o &#224; dura&#231;&#227;o da onda P pelo ECGAR, os valores p foram os seguintes: 0,001 para o AE e VAE e de 0,024 para Aesc, n&#227;o havendo correla&#231;&#227;o com as demais medidas ecocardiogr&#225;ficas.</p>
    <p>Quanto ao Aesc e &#224;s medidas do ventr&#237;culo esquerdo, os coeficientes de Pearson foram os seguintes, com valor-p de 0,000: di&#226;metros diast&#243;lico, r = 0,62; e sist&#243;lico, r = 0,59; volumes diast&#243;lico, r = 0,53; e sist&#243;lico, r = 0,60; massa, r = 0,46; e FE pelos dois m&#233;todos, Teichholz e Simpson, r = 0,48 e 0,38, respectivamente.</p>
    <p>
      <bold>Curva de opera&#231;&#227;o caracter&#237;stica </bold>
    </p>
    <p>Aplicando-se a curva de opera&#231;&#227;o caracter&#237;stica para vari&#225;vel est&#225;vel de Aesc <underline>&gt;</underline> 28ml/m<sup>2</sup>, a DP apresentou uma &#225;rea abaixo da curva de 0,67 e p = 0,015, sendo a melhor medida quando comparada com as demais (dura&#231;&#227;o da onda P pelo ECG e pelo ECGAR). Considerando-se como valor alterado a DP <underline>&gt;</underline> 40 ms e como padr&#227;o de refer&#234;ncia Aesc <underline>&gt;</underline> 28 ml/m<sup>2</sup> , o valor preditivo positivo da DP foi de 87,5% e o valor preditivo negativo foi de 76,9%.</p>
    <p>
      <bold>Eventos cl&#237;nicos </bold>
    </p>
    <p>Durante o per&#237;odo de seguimento ambulatorial foram constatados os seguintes eventos: interna&#231;&#227;o por IC descompensada em seis pacientes, fibrila&#231;&#227;o atrial em sete pacientes (sendo sintom&#225;tica em tr&#234;s pacientes), acidente vascular encef&#225;lico em tr&#234;s pacientes, taquicardias ventriculares em sete pacientes, morte card&#237;aca s&#250;bita recuperada em um paciente, tromboembolismo pulmonar em um paciente e &#243;bito por causas card&#237;acas em sete pacientes. Dois pacientes foram submetidos &#224; terapia de ressincroniza&#231;&#227;o card&#237;aca e quatro ao transplante card&#237;aco.</p>
    <p>Vinte e um pacientes apresentaram um ou mais desses eventos durante o seguimento cl&#237;nico de 26,5 &#177; 8,0 meses. N&#227;o houve perdas de acompanhamentos dos pacientes, sendo, entretanto, o per&#237;odo de seguimento entre 15 dias e 35 meses, de acordo com a ocorr&#234;ncia ou n&#227;o de eventos cardiovasculares.</p>
    <p>Comparando-se as vari&#225;veis cl&#237;nicas, eletrocardiogr&#225;ficas e ecocardiogr&#225;ficas, por meio da an&#225;lise univariada pelo teste de Mann-Whitney, entre os grupos de pacientes sem e com eventos cardiovasculares, foram obtidos os valores dispostos na <xref ref-type="table" rid="aop312tab3">Tabela 3</xref>.</p>
    <p content-type="asset">
      <table-wrap id="aop312tab3">
        <graphic xlink:href="1678-4170-abc-100-01-0067-00115-gt03.jpg"/></table-wrap>
    </p>
    <p>Aplicando-se a curva de opera&#231;&#227;o caracter&#237;stica, considerando-se a vari&#225;vel est&#225;vel a ocorr&#234;ncia de eventos cardiovasculares, a vari&#225;vel Aesc apresentou uma &#225;rea sob a curva de 0,80 (p = 0,000, intervalo de confian&#231;a de 95% de 0,69 a 0,90); o melhor ponto de corte foi em 29,3 ml/m<sup>2</sup>, cuja sensibilidade foi de 94,7% e especificidade de 55,4%.</p>
    <p>Por meio da an&#225;lise multivariada por <italic>Stepwise</italic>, somente as vari&#225;veis AE e Aesc foram significantes, com p = 0,001 e p = 0,022, respectivamente.</p>
    <p>
      <bold>Curvas de sobrevida </bold>
    </p>
    <p>Utilizando a curva de Kaplan-Meier e considerando como base progn&#243;stica a ocorr&#234;ncia de eventos, foram constru&#237;das curvas de sobrevida em rela&#231;&#227;o &#224;s vari&#225;veis Aesc <underline>&gt;</underline> 28 ml/m<sup>2</sup>, Aesc <underline>&gt;</underline> 32ml/m<sup>2</sup> e &#224;s etiologias chag&#225;sica e n&#227;o chag&#225;sica e isqu&#234;mica e n&#227;o isqu&#234;mica. Foi aplicado o teste de <italic>Log rank</italic> (Mantel-Cox) para comparar as curvas. Os dados se encontram foram plotados nas <xref ref-type="fig" rid="aop312fig1">Figuras 1</xref>, <xref ref-type="fig" rid="aop312fig2">2</xref> e <xref ref-type="fig" rid="aop312fig3">3</xref>.</p>
    <p content-type="asset">
      <fig id="aop312fig1">
        <graphic xlink:href="1678-4170-abc-100-01-0067-00115-gf01.jpg"/></fig>
    </p>
    <p content-type="asset">
      <fig id="aop312fig2">
        <graphic xlink:href="1678-4170-abc-100-01-0067-00115-gf02.jpg"/></fig>
    </p>
    <p content-type="asset">
      <fig id="aop312fig3">
        <graphic xlink:href="1678-4170-abc-100-01-0067-00115-gf03.jpg"/></fig>
    </p>
    <p>Durante o seguimento, 13 (47,0%) pacientes com IC de etiologia chag&#225;sica apresentaram eventos cardiovasculares contra oito (21,3%) daqueles n&#227;o chag&#225;sicos. Tomando-se por base a etiologia isqu&#234;mica, somente dois pacientes (14,2%) apresentaram eventos contra 29,6% dos pacientes com IC de etiologia n&#227;o isqu&#234;mica, sem diferen&#231;a estat&#237;stica.</p>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>O principal achado desse estudo foi a correla&#231;&#227;o entre o Aesc e os eventos cardiovasculares, sendo aquela medida uma preditora independente da evolu&#231;&#227;o dos pacientes com IC com uma raz&#227;o de chance de 14,4 para o Aesc <underline>&gt;</underline> 28 ml/m<sup>2</sup> e de 18,0 para o Aesc <underline>&gt;</underline> 32 ml/m<sup>2</sup>. Al&#233;m disso, os pacientes com IC de etiologia chag&#225;sica apresentaram uma menor sobrevida livre daqueles eventos em rela&#231;&#227;o aos pacientes n&#227;o chag&#225;sicos.</p>
    <p>Em pacientes com IC, a &#225;rea do AE &#233; considerada um marcador importante de progn&#243;stico, relacionando-se seu aumento &#224; mortalidade e interna&#231;&#227;o devido &#224; piora do quadro de IC, independentemente da idade, da classe funcional, da fra&#231;&#227;o de eje&#231;&#227;o e do padr&#227;o restritivo de enchimento, como demonstrado em uma meta-an&#225;lise de 18 estudos, com casu&#237;stica total de 1157 pacients<sup>16</sup>. Neste mesmo estudo, foi obtido o &#237;ndice do AE, pelo quociente entre a &#225;rea do AE e a superf&#237;cie corp&#243;rea, em 721 pacientes, observando-se que valores <underline>&gt;</underline> 9,85 cm<sup>2</sup>/m<sup>2</sup> apresentavam uma raz&#227;o de chance de 2,35. N&#227;o foi feita a an&#225;lise das medidas da onda P e tampouco o volume do AE. Outro importante estudo do mesmo autor<sup>21</sup>, realizado tomando-se como medida o Aesc em 102 pacientes com miocardiopatia dilatada, verificou que essa medida estava associada tamb&#233;m com mortalidade e necessidade de transplante card&#237;aco. O melhor ponto de corte para o valor m&#225;ximo de Aesc foi de 68,5 ml/m<sup>2</sup>, com uma sensibilidade de 65% e uma raz&#227;o de chance de 3,8. Por&#233;m, nesse estudo 12% dos pacientes estavam em ritmo de fibrila&#231;&#227;o atrial. Assim, o presente estudo apresentou associa&#231;&#227;o, correla&#231;&#227;o e valor progn&#243;stico independente do Aesc, indo de encontro aos achados da literatura. Entretanto, os aspectos de relev&#226;ncia do nosso estudo foram o uso de valores considerados na literatura para eventos cardiovasculares de menor magnitude, de 28 ml/m<sup>2 20 </sup>e 32 ml/m<sup>2 14</sup>, a casu&#237;stica composta de pacientes com IC e todos em ritmo sinusal, incluindo outras etiologias al&#233;m da idiop&#225;tica e isqu&#234;mica. Adicionado a essa metodologia, foram realizadas as medidas da onda P pelo ECG, obtendo-se sua dispers&#227;o, e por meio do ECGAR, o que n&#227;o foi realizado naqueles principais estudos sobre o tema.</p>
    <p>As anormalidades da onda P s&#227;o associadas ao aumento do AE, &#224; hipertens&#227;o nesta c&#226;mara, aos dist&#250;rbios da condu&#231;&#227;o intra-atrial ou &#224; combina&#231;&#227;o de todos esses elementos. O AE permanece diretamente exposto &#224; aumentada press&#227;o diast&#243;lica final do VE, o que resulta em aumento da press&#227;o intra-atrial para manter o fluxo adequado, elevando a tens&#227;o nas paredes atriais e causando dilata&#231;&#227;o e estiramento das fibras mioc&#225;rdicas. Em pacientes com IC, foi demonstrado que a dura&#231;&#227;o da onda P pelo ECGAR depende mais da press&#227;o intra-atrial que da dimens&#227;o do AE<sup>19</sup>.</p>
    <p>Entretanto, no presente estudo, apesar da correla&#231;&#227;o entre DP e a dura&#231;&#227;o da onda P pelo ECGAR e as medidas de AE, e do valor preditivo positivo de 87,5% para DP <underline>&gt;</underline> 40 ms em rela&#231;&#227;o ao Aesc <underline>&gt;</underline> 28 ml/m<sup>2</sup>, o coeficiente de Pearson foi menor que 0,50, sugerindo um grau moderado de depend&#234;ncia estat&#237;stica linear entre aquelas vari&#225;veis. Esse achado tamb&#233;m pode estar relacionado &#224; baixa sensibilidade do ECG em rela&#231;&#227;o ao ecocardiograma no que tange &#224;s sobrecargas de AE, ou ainda ao menor valor de corte para o Aesc no qual nos baseamos. N&#227;o houve correla&#231;&#227;o entre a DP e a FE em virtude da homogeneidade da casu&#237;sta composta de pacientes com cl&#237;nica de IC e FE m&#233;dia de 37% pelo m&#233;todo de Simpson.</p>
    <p>Analisando os dados cl&#237;nicos da compara&#231;&#227;o de vari&#225;veis entre os grupos sem e com eventos, observou-se que as vari&#225;veis que tradicionalmente j&#225; foram correlacionadas ao pior progn&#243;stico<sup>1,2</sup>, como a classe funcional e a dimens&#227;o do AE e do ventr&#237;culo esquerdo e sua FE, tamb&#233;m apresentaram essa associa&#231;&#227;o na an&#225;lise univariada. Por&#233;m, por meio da an&#225;lise multivariada, somente as vari&#225;veis AE e Aesc foram preditoras independentes de eventos cardiovasculares.</p>
    <p>Apesar da propor&#231;&#227;o de somente 21,7% dos pacientes da casu&#237;sta apresentar a etiologia chag&#225;sica, foi observado seu pior progn&#243;stico, com uma raz&#227;o de chance de 3,2 de ocorr&#234;ncia de eventos cardiovasculares em rela&#231;&#227;o aos n&#227;o chag&#225;sicos. Essa pior evolu&#231;&#227;o est&#225; em conson&#226;ncia com os dados da literatura<sup>22</sup>, sendo atribu&#237;do esse pior progn&#243;stico ao comprometimento hemodin&#226;mico, &#224; magnitude maior da disfun&#231;&#227;o sist&#243;lica e &#224; ativa&#231;&#227;o humoral e inflamat&#243;ria.</p>
    <p>Em rela&#231;&#227;o a toda a popula&#231;&#227;o do estudo em quest&#227;o, foi observada a taxa de mortalidade card&#237;aca de 8,9% durante o tempo m&#233;dio de 2,2 anos. Dados no Brasil mostraram taxa anual de mortalidade de 6,3% de pacientes com IC, alcan&#231;ando o valor de 11% naqueles com mais de 80 anos<sup>1</sup>. Dados estat&#237;sticos da American Heart Association evidenciaram a taxa anual de mortalidade de 4,9% para aqueles com, pelo menos, 20 anos, alcan&#231;ando uma taxa de 50% em cinco anos<sup>3</sup>. E entre aqueles pacientes com IC que foram hospitalizados e receberam alta, a mortalidade geral foi de 26% durante o seguimento de 9,9 meses, sendo de 10,7% a mortalidade devido &#224; IC<sup>23</sup>. Dessa maneira, a taxa de mortalidade de nossa casu&#237;stica foi similar ou inferior &#224;s taxas da literatura, segundo as diferen&#231;as da popula&#231;&#227;o estudada, se em regime ambulatorial ou ap&#243;s a alta hospitalar, as diferentes classes funcionais, idade e etiologias.</p>
    <p>
      <bold>Conclus&#245;es</bold>
    </p>
    <p>A dispers&#227;o da onda P n&#227;o esteve correlacionada &#224; ocorr&#234;ncia de eventos cardiovasculares nessa casu&#237;stica de pacientes com IC. O Aesc foi um preditor independente de ocorr&#234;ncia daqueles eventos, com uma raz&#227;o de chance de 14,4 para o Aesc <underline>&gt;</underline> 28 ml/m<sup>2</sup> e de 18,0 para o Aesc <underline>&gt;</underline> 32 ml/m<sup>2</sup>. Pacientes com IC de etiologia chag&#225;sica apresentaram menor sobrevida livre daqueles eventos em rela&#231;&#227;o aos pacientes n&#227;o chag&#225;sicos, com uma raz&#227;o de chance de 3,2.</p>
    <p>
      <bold>Potencial Conflito de Interesses</bold>
    </p>
    <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
    <p>
      <bold>Fontes de Financiamento</bold>
    </p>
    <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
    <p>
      <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
    </p>
    <p>Este artigo &#233; parte de disserta&#231;&#227;o de Mestrado de Nadya Mendes Kazzaz pela Universidade Federal de Minas Gerais.</p>
    <p>
      <fn id="end" fn-type="corresp">
        <p>Correspond&#234;ncia:</p>
        <p> Rose Mary Ferreira Lisboa da Silva &#149; </p>
        <p> Faculdade de Medicina da UFMG - Av. Alfredo Balena, 190, sala 246, bairro Santa Efig&#234;nia, CEP 30.130-100 - Belo Horizonte/MG, Brasil </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="roselisboa@uol.com.br">roselisboa@uol.com.br</email>
        </p>
      </fn>
    </p>
    <p>Artigo recebido em 25/05/12; revisado recebido em 15/08/12; aceito em 15/08/12.</p>
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        <element-citation publication-type="journal">
          <article-title>Causes of death and rehospitalization in patients hospitalized with worsening heart failure and reduced left ventricular ejection fraction: results from Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) program</article-title>
          <source>Am Heart J</source>
          <date>
            <year>2010</year>
          </date>
          <fpage>841</fpage>
          <lpage>9</lpage>
          <issue>5</issue>
          <volume>159</volume>
          <person-group person-group-type="author">
            <name>
              <surname>O'Connor CM</surname>
            </name>
            <name>
              <surname>Miller</surname>
              <given-names>AB</given-names>
            </name>
            <name>
              <surname>Blair</surname>
              <given-names>JE</given-names>
            </name>
            <name>
              <surname>Konstam</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Wedge</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Bahit</surname>
              <given-names>MC</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
    </ref-list>
  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">P-wave dispersion and left atrial volume index as predictors in heart failure</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>BACKGROUND: Studies have shown that P-wave dispersion (PWD) and left atrial volume index (LAVi) are predictors of cardiovascular events (CE). OBJECTIVE: To verify the prognostic value of PWD and LAVi for the occurrence of CE in patients with heart failure (HF). METHODS: This was a longitudinal prospective study of 78 consecutive patients with a mean age of 47.2 years, of which 52 were males. Patients had stable HF and underwent clinical evaluation, electrocardiogram and echocardiogram assessments, with a follow-up of 26.5 months. RESULTS: The means of the variables were: 50 ms for PWD and 35.5 mL/m&#178; for LAVi. Considering PWD &gt; 40 ms and, as reference, LAVi &gt; 28 mL/m&#178;, the positive predictive value of PWD was 87.5% and the negative predictive value was 76.9%. During follow-up, 21 patients had CE. There was an association between left atrial measurements, left ventricular volumes, ejection fraction and CE. There was no association between PWD and CE. At the multivariate analysis, the left atrium and LAVi were predictors of events (p = 0.00 and 0.02). Through the operating characteristic curve for the variable stable CE, areas of 0.80 and 0.69 were obtained for LAVi (p = 0.00) and LAVi &gt; 28 mL/m&#178; (p = 0.01). Survival curves (Kaplan-Meier) free of those events for LAVi &gt; 28 mL/m&#178; and for Chagas disease etiology showed an odds ratio of 14.4 (p = 0.00) and 3.2 (p = 0.03). There was no difference in outcome between patients with ischemic and nonischemic heart failure. CONCLUSION: PWD was not correlated to CE. LAVi was an independent predictor of CE, and chagasic patients showed worse outcomes.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Heart Failure</kwd>
        <kwd>P Wave</kwd>
        <kwd>Heart Atria</kwd>
        <kwd>Electrocardiography</kwd>
        <kwd>Atrial Fibrillation</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <fn id="top-body2">
          <label>
            <bold>P-wave dispersion and left atrial volume index as predictors in heart failure</bold>
          </label>
          <p>
            <bold>Rose Mary Ferreira Lisboa da Silva<sup>I</sup>; Nadya Mendes Kazzaz<sup>I, II</sup>; Ros&#225;lia Morais Torres<sup>I</sup>; Maria da Consola&#231;&#227;o Vieira Moreira<sup>I</sup></bold>
          </p>
        </fn>
      </p>
      <p><sup>I</sup>Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil</p>
      <p><sup>II</sup>Cl&#237;nica ECOGRAF N&#250;cleo de Diagn&#243;stico N&#227;o Invasivo, Belo Horizonte, MG, Brazil</p>
      <p>Mailing Address</p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p><bold>BACKGROUND: </bold>Studies have shown that P-wave dispersion (PWD) and left atrial volume index (LAVi) are predictors of cardiovascular events (CE).</p>
      <p><bold>OBJECTIVE: </bold>To verify the prognostic value of PWD and LAVi for the occurrence of CE in patients with heart failure (HF).</p>
      <p><bold>METHODS: </bold>This was a longitudinal prospective study of 78 consecutive patients with a mean age of 47.2 years, of which 52 were males. Patients had stable HF and underwent clinical evaluation, electrocardiogram and echocardiogram assessments, with a follow-up of 26.5 months.</p>
      <p><bold>RESULTS: </bold>The means of the variables were: 50 ms for PWD and 35.5 mL/m<sup>2</sup> for LAVi. Considering PWD <underline>&gt;</underline> 40 ms and, as reference, LAVi <underline>&gt;</underline> 28 mL/m<sup>2</sup>, the positive predictive value of PWD was 87.5% and the negative predictive value was 76.9%. During follow-up, 21 patients had CE. There was an association between left atrial measurements, left ventricular volumes, ejection fraction and CE. There was no association between PWD and CE. At the multivariate analysis, the left atrium and LAVi were predictors of events (p = 0.00 and 0.02). Through the operating characteristic curve for the variable stable CE, areas of 0.80 and 0.69 were obtained for LAVi (p = 0.00) and LAVi <underline>&gt;</underline> 28 mL/m<sup>2</sup> (p = 0.01). Survival curves (Kaplan-Meier) free of those events for LAVi <underline>&gt;</underline> 28 mL/m<sup>2</sup> and for Chagas disease etiology showed an odds ratio of 14.4 (p = 0.00) and 3.2 (p = 0.03). There was no difference in outcome between patients with ischemic and nonischemic heart failure.</p>
      <p><bold>CONCLUSION:</bold> PWD was not correlated to CE. LAVi was an independent predictor of CE, and chagasic patients showed worse outcomes. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0)</p>
      <p><bold>Keywords:</bold> Heart Failure; P Wave; Heart Atria; Electrocardiography; Atrial Fibrillation.</p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p>Heart failure (HF) is a serious public health problem and is considered pandemic in the XXI century, as it shows an increase in prevalence, with high morbidity - 83% of patients having at least one hospitalization and 43% with at least four hospitalizations after diagnosis. Despite advances in treatment and improved survival in recent decades, the annual mortality rates for heart failure are still high, reaching proportions of all deaths of 40.5% in men and 59.5% in women, considering all ages<sup>1-3</sup>.</p>
      <p>Thus, risk stratification in stable patients is important to predict events related to this disease, with the objective of achieving a more rational approach. Studies have demonstrated a correlation between P-wave measurements, obtained through the conventional and/or high-resolution electrocardiogram, and the occurrence or recurrence of atrial fibrillation (after electrical cardioversion or radiofrequency ablation)<sup>4-7</sup>; atrial arrhythmias in Brugada syndrome<sup>8</sup>, and after cardiac transplantation<sup>9</sup>; hypertrophy and left diastolic dysfunction in hypertensive patients<sup>10</sup>; HF<sup>11,12</sup>; and improvement in ejection fraction after cardiac resynchronization therapy<sup>13</sup>.</p>
      <p>Other studies have shown that left atrial enlargement, mainly determined by the left atrial volume index (LAVi) is a predictor of cardiovascular events such as mortality; HF; hospitalization; need for heart transplantation; higher incidence of cerebrovascular accident (CVA) and atrial fibrillation; acute myocardial infarction; and coronary artery bypass surgery<sup>14-17</sup>. Considering the HF picture, the prognostic studies on P-wave measurements in conjunction with those of the left atrium are scarce<sup>11,18</sup>, which motivated the present study. The main objective of this study is to correlate the P-wave measurements with left atrial volume and its index and verify the prognostic value of these measurements and other variables in stable patients with HF.</p>
      <p>
        <bold>Methods</bold>
      </p>
      <p>This was an observational, longitudinal and prospective study. The study population consisted of 78 consecutive and stable patients with HF, regardless of the etiology, with atrial sinus rhythm, of both genders, aged 18 and older, who agreed to participate in the study. Both the research project and the informed consent form (ICF) were approved by the Ethics and Research Committee of the Universidade Federal de Minas Gerais (UFMG) (protocol number 270/06).</p>
      <p>After the ICF was signed, the patients underwent clinical evaluation and a conventional 12-lead surface electrocardiogram (ECG), a high-resolution electrocardiogram (HRECG), and a transthoracic echocardiography. We excluded patients with valvular heart disease, pregnant women, patients with congenital heart disease, those who had undergone heart transplantation, and terminally-ill patients.</p>
      <p>The 12-lead ECG was performed at the speed of 50 mm/s and voltage of 20 mm/mV to allow measurement of the P-wave duration at the 12 leads and its dispersion (PWD), defined as the difference between its maximum and minimum values. The onset of the P-wave was defined as the point of the first visible upward departure of the trace from the bottom of the baseline for the positive waves, and as the point of the first downward departure from the top of the baseline for negative waves. The return of the bottom of the trace to the baseline in positive waves was considered to be the end of the P-wave<sup>18</sup>. After the recording, the measurements were performed by two trained and independent observers before the echocardiogram was performed; these were blinded to patients' clinical condition, so as to analyze interobserver variability.</p>
      <p>A promediated ECG signal was acquired, amplified and filtered, after being obtained through orthogonal X, Y and Z leads (HRECG) with final noise &lt; 0.5 microvolts and a number of ectopic beats lower than 1% of the total number of beats. The recording was acquired during a 16-minute monitoring using a digital multi-cardiographer, with patients in the supine position in a room with noise insulation. The signal evaluation was made after rigorous manual editing of recordings. The P-wave duration was measured manually from the onset to the end of the signal, which had an amplitude at least twice the noise level<sup>19</sup>.</p>
      <p>The patients also underwent an echocardiographic assessment performed simultaneously by two observers. Left atrial volume was obtained through the available software, using atrial measurements in the cephalocaudal, latero-lateral and oblique axes. The cutoff value used for left atrial volume index (LAVi) - left atrial volume/body surface area, was 28 mL/m<sup>2</sup> and 32 mL/m<sup>2</sup>, according to literature references<sup>14,20</sup>.</p>
      <p>The mean follow-up duration was 26.5 &#177; 8.0 months. The clinical complications were recorded, as well as any hospitalizations.</p>
      <p>
        <bold>Statistical Analysis </bold>
      </p>
      <p>For data analysis, we used SPSS (Statistical Package for Social Sciences) software, release 14.0. The results were expressed as numbers and proportions for discrete variables, and measures of central tendency and dispersion for continuous variables. The Mann-Whitney test, the Kruskal-Wallis test, and the Chi-square or Fisher test were used, when appropriate, to compare differences between continuous and discrete variables, respectively. The correlation between variables was performed by Pearson's coefficient. Kappa agreement was used to analyze the interobserver variability. The operating characteristic curve was used to determine sensitivity and specificity for PWD and LAVi. Logistic regression analysis was used through the stepwise method, the dependent variable being the occurrence of cardiovascular events, considering the variables with p <underline>&lt;</underline> 0.10 in the univariate analysis. Survival analysis was performed using the Kaplan-Meier curve, considering the measurement of LAVi <underline>&gt;</underline> 28 mL/m<sup>2</sup> and <underline>&gt;</underline> 32 mL/m<sup>2</sup> and HF etiology. The level of rejection of the null hypothesis was set at 0.05.</p>
      <p>
        <bold>Results</bold>
      </p>
      <p>The sample consisted of 78 patients, of which 52 (66.6%) were males and 26 (33.3%) females. The mean age was 47.2 &#177; 13.2 years, ranging from 19 to 71 years. The other clinical data are shown in <xref ref-type="table" rid="en_aop312tab1-body2">Table 1</xref>. Concerning the etiology of the cardiomyopathy, 23 patients had idiopathic etiology; 17 had Chagas disease; 15 had ischemic etiology; nine patients were hypertensive; six had alcoholic etiology; five had peripartum etiology; and two had dilated cardiomyopathy due to myocarditis. Regarding lifestyle, smoking habit was reported by 29 patients (37.2%), and alcohol consumption by 21 patients (26.6%).</p>
      <p content-type="asset">
        <table-wrap id="en_aop312tab1-body2">
          <graphic xlink:href="1678-4170-abc-100-01-0067-00115-gt01-en.jpg"/></table-wrap>
      </p>
      <p>Regarding comorbidities, nineteen patients had hypertension, 16 had diabetes mellitus, eight had hypothyroidism, and four had chronic kidney disease. In relation to drug treatment, 41 patients were taking angiotensin enzyme inhibitor; 24 used angiotensin receptor blocker; 59 used furosemide; 53 used spironolactone; 10 used thiazide; 50 used carvedilol; 3 used metoprolol; 47 used digoxin; 10 used aspirin; 11 used statin; and 15 used dicumarinic therapy.</p>
      <p>ECG measurement means were obtained: P-wave duration in lead D2: 120.0 &#177; 14.6 ms; PWD: 50 &#177; 14.6 ms; duration of the P-wave at HRECG: 114.0 &#177; 20.8 ms (mean noise 0.3 &#177; 0.1 microvolt and number of acquired cycles = 975.6 &#177; 208.0). The interobserver variability in the P-wave measurements was performed by the Kappa test, with values of 0.69 for PWD, and 0.86 for the duration of the P-wave at the HRECG. It was considered an agreement between the two observers when the difference was <underline>&lt;</underline> 10 ms for the measurement of the P-wave through the conventional ECG, and <underline>&lt;</underline> 5 ms, at the HRECG.</p>
      <p><xref ref-type="table" rid="en_aop312tab2-body2">Table 2</xref> shows the measured means at the echocardiogram.</p>
      <p content-type="asset">
        <table-wrap id="en_aop312tab2-body2">
          <graphic xlink:href="1678-4170-abc-100-01-0067-00115-gt02-en.jpg"/></table-wrap>
      </p>
      <p>
        <bold>Association and correlation between variables</bold>
      </p>
      <p>When applying the Kruskal-Wallis test for the analysis of variables in patients according to chagasic, ischemic, and other types of etiology, a p value of 0.015 was obtained for age (47.1, 56.2, and 44.6 years, respectively). There was no significant difference in relation to other variables, whether clinical, electrocardiographic or echocardiographic ones. Gender did not influence the etiology of heart failure (except for peripartum etiology).</p>
      <p>Pearson's coefficients between the PWD and the echocardiographic variables, such as of the left atrial (LA) diameter, LA volume (LAV), and LAVi, as well as systolic and diastolic diameters of the left ventricle (LV) showed a p value of 0.00 for each of them (r = 0.47, 0.42, 0.37, 0.46, 0.40, respectively). There was no correlation between PWD and ejection fraction (EF), either by the Teicholtz method (p = 0.054) or the Simpson method (p = 0.153). Regarding the P-wave duration by the LAVi, p values were as follows: 0.001 for LA and LAV, and 0.024 for LAVi, with no correlation with the other echocardiographic measurements.</p>
      <p>As for the LAVi and LV measurements, Pearson's coefficients were as follows, with a p value of 0.000: diastolic diameter, r = 0.62, and systolic diameter, r = 0.59, diastolic volume, r = 0, 53, and systolic volume, r = 0.60; mass, r = 0.46, and EF by both methods, Teicholtz and Simpson, r = 0.48 and 0.38, respectively.</p>
      <p>
        <bold>Operating characteristic curve </bold>
      </p>
      <p>When applying the operating characteristic curve for the stable variable of LAVi <underline>&gt;</underline> 28 mL/m<sup>2</sup>, PWD showed an area under the curve of 0.67 and p = 0.015 to be the best measurement when compared with the others (P-wave duration at the ECG and HRECG). Considering PWD <underline>&gt;</underline> 40 ms as altered value, and LAVi <underline>&gt;</underline> 28 mL/m<sup>2 </sup>as a reference standard value, the positive predictive value of PWD was 87.5% and the negative predictive value was 76.9%.</p>
      <p>
        <bold>Clinical events </bold>
      </p>
      <p>The following events were recorded during follow-up: hospitalization due to decompensated HF in six patients; atrial fibrillation in seven patients (symptomatic in three patients); CVA in three patients; ventricular tachycardia in seven patients; recovered sudden cardiac arrest in one patient; pulmonary embolism in one patient; and death from cardiac causes in seven patients. Two patients underwent cardiac resynchronization therapy, and four underwent heart transplantation.</p>
      <p>Twenty-one patients had one or more of these events during a follow-up of 26.5 &#177; 8.0 months. There was no patient loss to follow-up; however, the follow-up period comprised between 15 days and 35 months, according to the occurrence of cardiovascular events.</p>
      <p><xref ref-type="table" rid="en_aop312tab3-body2">Table 3</xref> shows the comparison of the clinical, electrocardiographic, and echocardiographic variables by means of univariate analysis using the Mann-Whitney test between the groups of patients with and without cardiovascular events.</p>
      <p content-type="asset">
        <table-wrap id="en_aop312tab3-body2">
          <graphic xlink:href="1678-4170-abc-100-01-0067-00115-gt03-en.jpg"/></table-wrap>
      </p>
      <p>When applying the characteristic operating curve, considering the occurrence of cardiovascular events as the stable variable, the variable LAVi showed an area under the curve of 0.80 (p = 0.000, 95% confidence interval of 0.69 to 0.90); the best cutoff was 29.3 mL/m<sup>2</sup>, of which sensitivity was 94.7% and specificity was 55.4%.</p>
      <p>At the stepwise multivariate analysis, only the variables LA and LAVi were significant, with p = 0.001 and p = 0.022, respectively.</p>
      <p>
        <bold>Survival curves </bold>
      </p>
      <p>Using the Kaplan-Meier method and considering the occurrence of events as prognostic basis, survival curves were constructed in relation to variables LAVi <underline>&gt;</underline> 28 mL/m<sup>2</sup>, LAVi <underline>&gt;</underline> 32 mL/m<sup>2</sup>, and the Chagasic and non-Chagasic and ischemic and nonischemic etiologies. The Log rank test (Mantel-Cox) was applied to compare the curves. The data found were plotted in <xref ref-type="fig" rid="en_aop312fig1-body2">Figures 1</xref>, <xref ref-type="fig" rid="en_aop312fig2-body2">2</xref>, and <xref ref-type="fn" rid="en_aop312fig3-body2">3</xref>. During follow-up, 13 (47.0%) patients with heart failure due to Chagas disease had cardiovascular events <italic>versus</italic> eight (21.3%) non-Chagasic ones. Considering the ischemic etiology, only two patients (14.2%) had events <italic>versus</italic> 29.6% of patients with nonischemic etiology of HF, with no statistical difference.</p>
      <p content-type="asset">
        <fig id="en_aop312fig1-body2">
          <graphic xlink:href="1678-4170-abc-100-01-0067-00115-gf01-en.jpg"/></fig>
      </p>
      <p content-type="asset">
        <fig id="en_aop312fig2-body2">
          <graphic xlink:href="1678-4170-abc-100-01-0067-00115-gf02-en.jpg"/></fig>
      </p>
      <p content-type="asset">
        <fn id="en_aop312fig3-body2">
          <p>
            <graphic xlink:href="1678-4170-abc-100-01-0067-00115-e01-en.jpg"/></p>
        </fn>
      </p>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>The main finding of this study was the correlation between LAVi and cardiovascular events, with that measure being an independent predictor of outcome of patients with HF with an odds ratio of 14.4 for LAVi <underline>&gt;</underline> 28 mL/m<sup>2</sup> and 18.0 for LAVi <underline>&gt;</underline> 32 mL/m<sup>2</sup>. Furthermore, patients with HF due to Chagas disease had a lower event-free survival compared to non-Chagasic ones.</p>
      <p>In patients with HF, the LA area is considered an important marker of prognosis, and its increase is related to mortality and hospitalization due to worsening of HF, regardless of age, functional class, ejection fraction and restrictive filling pattern, as shown in a meta-analysis of 18 studies, with a total sample of 1157 patients<sup>16</sup>. In this same study, the LA index was obtained through the ratio of the LA area and body surface in 721 patients, demonstrating that values <underline>&gt;</underline> 9.85 cm<sup>2</sup>/m<sup>2</sup> had an odds ratio of 2.35. There was no analysis of P-wave measurements or LA volume.</p>
      <p>Another important study by the same author<sup>21</sup>, which was performed by measuring LAVi in 102 patients with dilated cardiomyopathy, found that this measurement was also associated with mortality and need for heart transplantation. The best cutoff for the maximum value of LAVi was 68.5 mL/m<sup>2</sup>, with a sensitivity of 65% and an odds ratio of 3.8. However, in this study 12% of patients were in atrial fibrillation. Thus, the present study showed an association, correlation and independent prognostic value of LAVi, which are consistent with the literature.</p>
      <p>However, the relevant aspects of our study were the use of values considered to be of lesser magnitude in the literature for cardiovascular events (28 mL/m<sup>2 20</sup> and 32 mL/m<sup>2 14</sup>), a sample in which all patients had HF and sinus rhythm, and the inclusion of other etiologies in addition to ischemic and idiopathic etiologies. Additionally, P-wave measurements were carried out by ECG, obtaining its dispersion, and by HRECG, which was not performed in other studies that assessed the subject.</p>
      <p>P-wave abnormalities are associated with increased LA, hypertension in this chamber, disturbances of intra-atrial conduction or a combination of all these elements. The LA remains directly exposed to increased LV end-diastolic pressure, which results in increased intra-atrial pressure to maintain adequate flow, thus increasing the tension in the atrial walls and causing dilation and stretching of myocardial fibers. In patients with HF, it has been demonstrated that P-wave duration at the HRECG depends more on the intra-atrial pressure than on LA size<sup>19</sup>.</p>
      <p>However, in this study, in spite of the correlation between PWD and P-wave duration at the HRECG and LA measurements, and the positive predictive value of 87.5% for PWD <underline>&gt;</underline> 40 ms in relation to LAVi <underline>&gt;</underline> 28 mL/m<sup>2</sup>, Pearson's coefficient was &lt; 0.50, suggesting a moderate degree of statistical linear dependence between these variables. This finding may also be related to the low sensitivity of ECG in relation to echocardiography in regard to LA overloads, or the lower cutoff value for the LAVi on which it was based. There was no correlation between PWD and EF due to homogeneity of the sample, which consisted of patients with HF and mean EF of 37% by Simpson's method.</p>
      <p>Analyzing the clinical data when comparing variables between the groups with and without events, we observed that variables traditionally correlated with poor prognosis<sup>1,2</sup>, such as functional class and LA size and LV size and its EF, also showed this association in the univariate analysis. However, at the multivariate analysis, only variables LA and LAVi were independent predictors of cardiovascular events.</p>
      <p>Although only 21.7% of the sample patients had Chagas disease, a worse prognosis was observed for this group, with an odds ratio of 3.2 for cardiovascular events compared to non-Chagasic patients. This worse outcome is in agreement with literature data<sup>22</sup>, and this poor prognosis is attributed to greater hemodynamic impairment, greater magnitude of systolic dysfunction and humoral and inflammatory activation.</p>
      <p>In relation to the entire population of the present study, we observed a cardiac mortality rate of 8.9% during the mean period of 2.2 years. Data in Brazil showed an annual mortality rate of 6.3% of patients with HF, reaching a value as high as 11% in those older than 80 years<sup>1</sup>.</p>
      <p>Statistical data from the American Heart Association showed an annual mortality rate of 4.9% for those aged at least 20 years, reaching a rate of 50% in five years<sup>3</sup>. Among those patients with HF who were hospitalized and were discharged, the overall mortality was 26% during a follow-up of 9.9 months, with 10.7% mortality due to HF<sup>23</sup>. Therefore, the mortality rate of our patients was similar or lower than those in the literature, according to differences in study population, whether outpatient or after hospital discharge, different functional classes, age range and etiologies.</p>
      <p>
        <bold>Conclusion</bold>
      </p>
      <p>P-wave dispersion was not correlated with the occurrence of cardiovascular events in this series of patients with HF. LAVi was an independent predictor of occurrence of these events, with an odds ratio of 14.4 for LAVi <underline>&gt;</underline> 28 mL/m<sup>2</sup> and 18.0 for LAVi <underline>&gt;</underline> 32 mL/m<sup>2</sup>. Patients with heart failure due to Chagas' disease had lower event-free survival compared to those patients without Chagas' disease, with an odds ratio of 3.2.</p>
      <p>
        <bold>Potential Conflict of Interest</bold>
      </p>
      <p>No potential conflict of interest relevant to this article was reported.</p>
      <p>
        <bold>Sources of Funding</bold>
      </p>
      <p>There were no external funding sources for this study.</p>
      <p>
        <bold>Study Association</bold>
      </p>
      <p>This article is part of the thesis of master submitted by Nadya Mendes Kazzaz, from Universidade Federal de Minas Gerais.</p>
      <p>
        <bold>References</bold>
      </p>
    </body>
  </sub-article>
</article>
