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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">djxfDnnLZrfLkMbrmvkVDtc</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2013003200007</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(13)10100600007</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20130214</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>&#205;ndices de onda P na predi&#231;&#227;o de recorr&#234;ncia de fibrila&#231;&#227;o atrial ap&#243;s isolamento da veia pulmonar</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Salah</surname>
            <given-names>Ahmed</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Zhou</surname>
            <given-names>Shenghua</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Liu</surname>
            <given-names>Qiming</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Yan</surname>
            <given-names>Hui</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="state"/>
        </addr-line>
        <institution content-type="orgname">Central South University</institution>
        <institution content-type="orgdiv1">Second Xiangya Hospital </institution>
        <country country="CN">China</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>12</month>
        <year>2013</year>
      </pub-date>
      <volume>101</volume>
      <issue>6</issue>
      <fpage>519</fpage>
      <lpage>527</lpage>
      <history>
        <date date-type="received">
          <day>19</day>
          <month>02</month>
          <year>2013</year>
        </date>
        <date date-type="accepted">
          <day>05</day>
          <month>08</month>
          <year>2013</year>
        </date>
        <date date-type="rev-recd">
          <day>29</day>
          <month>07</month>
          <year>2013</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: &#205;ndices de ondas P s&#227;o marcadores interessantes para prever recorr&#234;ncias de fibrila&#231;&#227;o atrial (FA) p&#243;s abla&#231;&#227;o. OBJETIVO: Esse estudo avalia o valor dos &#237;ndices de onda P para prever recorr&#234;ncias ap&#243;s isolamento da veia pulmonar (IVP) em pacientes com fibrila&#231;&#227;o atrial parox&#237;stica. M&#201;TODOS: Foram selecionados 198 pacientes (57 &#177; 8 anos, 150 homens) com FA parox&#237;stica sintom&#225;tica refrat&#225;ria a medicamentos submetidos ao IVP em nosso hospital. Um eletrocardiograma de 12 deriva&#231;&#245;es foi utilizado para medir a dura&#231;&#227;o da onda P na deriva&#231;&#227;o II, a for&#231;a terminal de P (FTP) na deriva&#231;&#227;o V1, o eixo e a dispers&#227;o da onda P. RESULTADOS: No acompanhamento de 9 &#177; 3 meses, as recorr&#234;ncias ocorreram em 60 (30,3%) pacientes. Os pacientes que apresentaram recorr&#234;ncia de FA tiveram maior dura&#231;&#227;o m&#233;dia de onda P (122,9 &#177; 10,3 versus 104,3 &#177; 14,2 ms, p &lt; 0,001), maior dispers&#227;o da onda P (40,7 &#177; 1,7 ms vs 36,6 &#177; 3,2 ms, p &lt; 0,001). A dura&#231;&#227;o da onda P &gt; 125 ms apresenta 60% de sensibilidade, especificidade de 90%, valor preditivo positivo (VPP) de 72% e valor preditivo negativo (VPN) de 83,7%, enquanto a dispers&#227;o da onda P &gt; 40 ms tem 78% de sensibilidade, 67% de especificidade, PPV 51% e VPN de 87,6%. 48/66 (72,7%) dos pacientes com FTP &lt; -0,04 mm/segundo vs 12/132 (9%) com FTP &gt; -0,04 mm/segundo tiveram recorr&#234;ncia de FA (p &lt; 0,001). O eixo da onda P n&#227;o diferiu entre os dois grupos. Na an&#225;lise multivariada, os &#237;ndices da onda P n&#227;o foram independentes do tamanho do &#225;trio esquerdo e da idade. CONCLUS&#213;ES: A dura&#231;&#227;o da onda P &gt; 125 ms, a dispers&#227;o da onda P &gt; 40 ms e FTP em V1 &lt; -0,04 mm/sec s&#227;o bons preditores cl&#237;nicos das recorr&#234;ncias de FA p&#243;s IVP em pacientes com fibrila&#231;&#227;o atrial parox&#237;stica; contudo, eles n&#227;o foram independentes do tamanho do &#225;trio esquerdo e da idade.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Fibrila&#231;&#227;o Atrial</kwd>
        <kwd>Onda P</kwd>
        <kwd>Fibrila&#231;&#227;o Ventricular</kwd>
        <kwd>Veias Pulmonares</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>01</day>
        <month>11</month>
        <year>2013</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>&#205;ndices de onda P na predi&#231;&#227;o de recorr&#234;ncia de fibrila&#231;&#227;o atrial ap&#243;s isolamento da veia pulmonar</bold>
    </p>
    <p>
      <bold>Ahmed Salah; Shenghua Zhou; Qiming Liu; Hui Yan</bold>
    </p>
    <p>Second Xiangya Hospital of Central South University - China</p>
    <p>
      <xref ref-type="corresp" rid="end">Endere&#231;o para correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>FUNDAMENTO:</bold> &#205;ndices de ondas P s&#227;o marcadores interessantes para prever recorr&#234;ncias de fibrila&#231;&#227;o atrial (FA) p&#243;s abla&#231;&#227;o. </p>
    <p><bold>OBJETIVO:</bold> Esse estudo avalia o valor dos &#237;ndices de onda P para prever recorr&#234;ncias ap&#243;s isolamento da veia pulmonar (IVP) em pacientes com fibrila&#231;&#227;o atrial parox&#237;stica. </p>
    <p><bold>M&#201;TODOS:</bold> Foram selecionados 198 pacientes (57 &#177; 8 anos, 150 homens) com FA parox&#237;stica sintom&#225;tica refrat&#225;ria a medicamentos submetidos ao IVP em nosso hospital. Um eletrocardiograma de 12 deriva&#231;&#245;es foi utilizado para medir a dura&#231;&#227;o da onda P na deriva&#231;&#227;o II, a for&#231;a terminal de P (FTP) na deriva&#231;&#227;o V1, o eixo e a dispers&#227;o da onda P. </p>
    <p><bold>RESULTADOS:</bold> No acompanhamento de 9 &#177; 3 meses, as recorr&#234;ncias ocorreram em 60 (30,3%) pacientes. Os pacientes que apresentaram recorr&#234;ncia de FA tiveram maior dura&#231;&#227;o m&#233;dia de onda P (122,9 &#177; 10,3 versus 104,3 &#177; 14,2 ms, p &lt; 0,001), maior dispers&#227;o da onda P (40,7 &#177; 1,7 ms vs 36,6 &#177; 3,2 ms, p &lt; 0,001). A dura&#231;&#227;o da onda P <underline>&gt;</underline> 125 ms apresenta 60% de sensibilidade, especificidade de 90%, valor preditivo positivo (VPP) de 72% e valor preditivo negativo (VPN) de 83,7%, enquanto a dispers&#227;o da onda P <underline>&gt;</underline> 40 ms tem 78% de sensibilidade, 67% de especificidade, PPV 51% e VPN de 87,6%. 48/66 (72,7%) dos pacientes com FTP <underline>&lt;</underline> -0,04 mm/segundo vs 12/132 (9%) com FTP &gt; -0,04 mm/segundo tiveram recorr&#234;ncia de FA (p &lt; 0,001). O eixo da onda P n&#227;o diferiu entre os dois grupos. Na an&#225;lise multivariada, os &#237;ndices da onda P n&#227;o foram independentes do tamanho do &#225;trio esquerdo e da idade. </p>
    <p><bold>CONCLUS&#213;ES:</bold> A dura&#231;&#227;o da onda P <underline>&gt;</underline> 125 ms, a dispers&#227;o da onda P <underline>&gt;</underline> 40 ms e FTP em V1 <underline>&lt;</underline> -0,04 mm/sec s&#227;o bons </p>
    <p> preditores cl&#237;nicos das recorr&#234;ncias de FA p&#243;s IVP em pacientes com fibrila&#231;&#227;o atrial parox&#237;stica; contudo, eles n&#227;o foram independentes do tamanho do &#225;trio esquerdo e da idade. </p>
    <p><bold>Palavras-chave:</bold> Fibrila&#231;&#227;o Atrial; Onda P; Fibrila&#231;&#227;o Ventricular; Veias Pulmonares.</p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p>A fibrila&#231;&#227;o atrial (FA) &#233; a arritmia card&#237;aca sustentada mais comum, cuja import&#226;ncia vem do fato de ser uma das principais e mais comuns causas de instabilidade circulat&#243;ria e acidente vascular cerebral. Os objetivos principais no tratamento de FA s&#227;o a frequ&#234;ncia card&#237;aca ou o controle do ritmo card&#237;aco e anticoagula&#231;&#227;o. Caso seja desejado o controle do ritmo e ele n&#227;o puder ser mantido atrav&#233;s de medica&#231;&#227;o ou cardiovers&#227;o, ent&#227;o a abla&#231;&#227;o por cateter pode ser tentada.</p>
    <p>A abla&#231;&#227;o por cateter com radiofrequ&#234;ncia (ACRF) da FA &#233; eficaz em 70-80% dos casos, mas as recidivas s&#227;o frequentes e, no momento, faltam marcadores precisos de recidivas<sup>1-4</sup>. A hist&#243;ria natural da AF &#233; caracterizada por mecanismos de autoperpetua&#231;&#227;o, altera&#231;&#245;es eletrofisiol&#243;gicas induzidas pela frequ&#234;ncia card&#237;aca e remodela&#231;&#227;o estrutural envolvendo o mioc&#225;rdio atrial<sup>5</sup>.</p>
    <p>O remodelamento atrial &#233; tanto el&#233;trico quanto estrutural; ele causa uma condu&#231;&#227;o el&#233;trica lenta e o alargamento do &#225;trio, que se reflete em mudan&#231;as na morfologia da onda P no eletrocardiograma (ECG). S&#227;o necess&#225;rios preditores para discriminar quem pode se beneficiar da abla&#231;&#227;o e assim economizar dinheiro, tempo e esfor&#231;o. A utiliza&#231;&#227;o dos par&#226;metros de ECG como preditores &#233; muito &#250;til, pois &#233; um m&#233;todo barato, vi&#225;vel e pode resultar em uma grande volume de informa&#231;&#227;o. Em nosso estudo, avaliamos o uso de &#237;ndices de onda P para prever a recorr&#234;ncia da fibrila&#231;&#227;o atrial ap&#243;s isolamento das veias pulmonares (IVP) em pacientes com fibrila&#231;&#227;o atrial parox&#237;stica.</p>
    <p>
      <bold>M&#233;todos</bold>
    </p>
    <p>
      <bold>Popula&#231;&#227;o</bold>
    </p>
    <p>Ap&#243;s consentimento informado, 198 pacientes consecutivos (57 &#177; 8 anos, 150 homens e 48 mulheres) com FA parox&#237;stica sintom&#225;tica refrat&#225;ria a medicamento, submetidos &#224; ACRF, foram inclu&#237;dos em nosso estudo. A FA foi classificada como parox&#237;stica quando os epis&#243;dios geralmente terminavam sem interven&#231;&#227;o e n&#227;o duravam mais de 7 dias, de acordo com as defini&#231;&#245;es das diretrizes da Sociedade Europeia de Cardiologia<sup>6</sup>.</p>
    <p>Antes do procedimento, todos os pacientes foram submetidos a um exame de ecocardiografia transtor&#225;cica abrangente para avaliar o tamanho e fun&#231;&#227;o do &#225;trio esquerdo (AE), a fun&#231;&#227;o do ventr&#237;culo esquerdo (VE), e para excluir doen&#231;a card&#237;aca estrutural; todos os pacientes tamb&#233;m foram submetidos &#224; ecocardiografia transesof&#225;gica imediatamente antes do procedimento de abla&#231;&#227;o, para excluir trombos no AE. As caracter&#237;sticas cl&#237;nicas est&#227;o resumidas na <xref ref-type="table" rid="aop_5444tab01">Tabela 1</xref>.</p>
    <p content-type="asset">
      <table-wrap id="aop_5444tab01">
        <graphic xlink:href="1678-4170-abc-101-06-0519-30214-gt01.jpg"/></table-wrap>
    </p>
    <p>
      <bold>Eletrocardiograma Padr&#227;o de 12 Deriva&#231;&#245;es (ECG)</bold>
    </p>
    <p>O ECG padr&#227;o de 12 deriva&#231;&#245;es foi realizado em todos os pacientes durante o ritmo sinusal, pouco antes do procedimento de abla&#231;&#227;o, usando equipamento dispon&#237;vel no mercado (MAC 1200 ST General Electric Medical Information Technology). O ECG gravado antes do procedimento de abla&#231;&#227;o foi utilizado para a an&#225;lise estat&#237;stica, enquanto outro ECG registrado ap&#243;s a abla&#231;&#227;o foi utilizado para confirmar que o paciente estava em ritmo sinusal p&#243;s-procedimento. Antes da abla&#231;&#227;o os ECGs foram registrados durante 10 segundos a uma velocidade inicial de varredura de 25 mm/s e calibrado para 1 mV/cm nas deriva&#231;&#245;es-padr&#227;o e, em seguida, a uma velocidade de varredura de 50 mm/s e calibrado a 2 mV/cm nas deriva&#231;&#245;es-padr&#227;o para obter outras medidas mais precisas. Foram realizados o escaneamento e digitaliza&#231;&#227;o dos sinais de ECG a partir de registros em papel utilizando um esc&#226;ner &#243;ptico para todos os registros de ECG; o in&#237;cio e o deslocamento da onda P foram definidos como o in&#237;cio da deflex&#227;o para cima do padr&#227;o de ondas P e seu retorno &#224; linha basal isoel&#233;trica na deriva&#231;&#227;o II<sup>7</sup>. Todos os seguintes par&#226;metros foram avaliados: dura&#231;&#227;o da onda P na deriva&#231;&#227;o II, for&#231;a terminal de P (FTP) na deriva&#231;&#227;o V1, eixo e dispers&#227;o da onda P. </p>
    <p>A dispers&#227;o da onda P foi medida manualmente, subtraindo a dura&#231;&#227;o m&#237;nima (Pmin) da onda P da dura&#231;&#227;o m&#225;xima (Pmax) da onda P (Pmax - Pmin), medidas por m&#250;ltiplas deriva&#231;&#245;es de ECG de superf&#237;cie a partir de um &#250;nico batimento e os valores m&#233;dios de tr&#234;s complexos foram calculados.</p>
    <p>O c&#225;lculo da FTP foi feito atrav&#233;s da medi&#231;&#227;o da dura&#231;&#227;o da onda P em segundos multiplicada pela amplitude da por&#231;&#227;o terminal negativa da onda P em V1, em mil&#237;metros, conforme mostrado na <xref ref-type="fig" rid="aop_5444fig01">Figura 1</xref>. Os pacientes foram divididos em dois grupos, o primeiro grupo para o qual a FTP era &gt; -0,04 mm/sec. (menor do que um pequeno quadrado) e o segundo grupo no qual a FTP era <underline>&lt;</underline> -0,04 mm/sec. (maior do que um pequeno quadrado).</p>
    <p content-type="asset">
      <fig id="aop_5444fig01">
        <graphic xlink:href="1678-4170-abc-101-06-0519-30214-gf01.jpg"/></fig>
    </p>
    <p>Um grupo de controle, incluindo 120 indiv&#237;duos normais (80 homens; 40 mulheres, m&#233;dia de idade 44 &#177; 17 anos), sem qualquer hist&#243;rico de FA, doen&#231;a card&#237;aca estrutural ou hipertens&#227;o, foi utilizado para definir os valores normais para as caracter&#237;sticas da onda P.</p>
    <p>Ap&#243;s a abla&#231;&#227;o, todos os pacientes foram avaliados de forma sistem&#225;tica no ambulat&#243;rio durante um acompanhamento m&#233;dio de 9 &#177; 3 meses. Os registros de ECG foram feitos em cada visita, e registros Holter de 24 horas foram programados ap&#243;s 3, 6 e 9 meses de acompanhamento. &#201; importante ressaltar que todos os pacientes foram encorajados a obter imediatamente um registro de ECG se experimentassem palpita&#231;&#245;es. Medicamentos antiarr&#237;tmicos foram interrompidos ap&#243;s o procedimento de abla&#231;&#227;o, a recorr&#234;ncia da AF foi definida como qualquer registro de AF no ECG ou um epis&#243;dio de mais de 30 s no registro de Holter de 24 horas.</p>
    <p>Os &#237;ndices de onda P em cada tra&#231;o de ECG foram avaliados por dois examinadores independentes cegos e as an&#225;lises de Bland-Altman foram realizadas para avaliar a reprodutibilidade inter e intra-observador da dura&#231;&#227;o da onda P, dispers&#227;o da onda P, eixo de onda P e for&#231;a terminal da onda P em V1. As medidas mostraram vieses m&#237;nimos (1,2 &#177; 1,1 e 1,3 &#177; 10 ms, respectivamente para a dura&#231;&#227;o da onda P), (1,6 &#177; 10 e 1,5 &#177; 10 ms, respectivamente, para a dispers&#227;o da onda P), (2 &#177; 8 e 2 &#177; 9 graus, respectivamente, para o eixo da onda P), (1,8 + 10 e 1,7 + 10 mmsec., respectivamente para a for&#231;a terminal da onda P em V1)<sup>8</sup>.</p>
    <p>
      <bold>Procedimento de abla&#231;&#227;o por cateter de radiofrequ&#234;ncia</bold>
    </p>
    <p>O procedimento de abla&#231;&#227;o foi realizado em jejum. A veia femoral direita foi usada para a inser&#231;&#227;o de cateteres, uma &#250;nica pun&#231;&#227;o transseptal foi realizada utilizando sistema de cateter-guia de acesso transseptal FAST-CATH (SL1 8.5 F St. Jude Medical). Dois cateteres foram inseridos: um cateter lasso duodecapolar para o registro da VP (introduzido pela bainha longa SL0 e posicionado no &#243;stio de cada VP sequencialmente), outro cateter de abla&#231;&#227;o de ponta irrigada de quatro mil&#237;metros para isolamento das veias pulmonares. A veia jugular direita interna foi utilizada para a inser&#231;&#227;o de um cateter decapolar dirig&#237;vel (2 mm de espa&#231;amento) no seio coron&#225;rio distal. Ap&#243;s a pun&#231;&#227;o transseptal, foi administrada de 5000 U de heparina em bolus por via intravenosa e o tempo de coagula&#231;&#227;o ativado foi mantido acima de 280 s durante todo o procedimento.</p>
    <p>Mapeamento eletro-anat&#244;mico tridimensional foi realizado em todos os casos utilizando o sistema CARTO3 (Biosence Webster, Johnson &amp; Johnson). A abla&#231;&#227;o por radiofrequ&#234;ncia visou criar les&#245;es circulares inicialmente aplicadas em toda a circunfer&#234;ncia da regi&#227;o antral das veias (ipsilateral veia-a-veia) com subsequente isolamento el&#233;ctrico, desde que n&#227;o tivesse sido obtido na aplica&#231;&#227;o circunferencial das les&#245;es. O isolamento de todas as quatro VPs foi realizado utilizando o cateter de abla&#231;&#227;o, guiado pelo cateter de mapeamento circunferencial na VP [30-35 W de pot&#234;ncia m&#225;xima, temperatura m&#225;xima de 40; dura&#231;&#227;o da aplica&#231;&#227;o de radiofrequ&#234;ncia (RF) de 60 s]. O desfecho da aplica&#231;&#227;o de RF era o IVP completo, demonstrado pela aus&#234;ncia de VP potenciais na VP durante o ritmo sinusal ou ritmo do seio coronariano, pela aus&#234;ncia de condu&#231;&#227;o no &#225;trio da VP-esquerda durante o ritmo da VP, e pela grava&#231;&#227;o de voltagem muito baixa (0,5 mV) dentro das VPs no mapa final de tens&#227;o. A reconfirma&#231;&#227;o do isolamento da VP foi realizada 30 minutos ap&#243;s a abla&#231;&#227;o para cada VP. Os pacientes foram acompanhados com eletrocardiograma (ECG) de monitoramento cont&#237;nuo por 24 horas e receberam alta do hospital dois dias ap&#243;s o procedimento.</p>
    <p>
      <bold>An&#225;lise Estat&#237;stica</bold>
    </p>
    <p>Os dados s&#227;o expressos como m&#233;dia &#177; desvio padr&#227;o para vari&#225;veis cont&#237;nuas e frequ&#234;ncias para vari&#225;veis categ&#243;ricas. As diferen&#231;as entre os grupos foram avaliadas por meio da estat&#237;stica qui-quadrado para as vari&#225;veis categ&#243;ricas e an&#225;lise de vari&#226;ncia para as vari&#225;veis cont&#237;nuas. Foi considerado significativo um valor de p &lt; 0,05. Tamb&#233;m foram realizados o coeficiente de correla&#231;&#227;o de Pearson e a an&#225;lise multivariada da regress&#227;o de Cox usando vari&#225;veis significativas. As an&#225;lises estat&#237;sticas foram realizadas utilizando o programa SPSS vers&#227;o 16.0 (SPSS Inc., Chicago, IL). Uma curva caracter&#237;stica de opera&#231;&#227;o do receptor (ROC) foi gerada para avaliar os &#237;ndices da onda P como preditor das recorr&#234;ncias de FA p&#243;s IVP e diferentes valores de corte para a dura&#231;&#227;o e dispers&#227;o da onda P foram escolhidos para avaliar a probabilidade de recorr&#234;ncia de fibrila&#231;&#227;o atrial. As taxas de n&#227;o ocorr&#234;ncia de FA de acordo com a dura&#231;&#227;o da onda P &lt; 125 ms e <underline>&gt;</underline> 125 ms, juntamente com dispers&#227;o da onda P &lt; 40 ms e <underline>&gt;</underline> 40 ms foram calculadas utilizando a an&#225;lise de Kaplan-Meier com o teste de log-rank. </p>
    <p>
      <bold>Resultados</bold>
    </p>
    <p>Os pacientes com FA parox&#237;stica em compara&#231;&#227;o aos casos de controle apresentaram maior dura&#231;&#227;o da onda P (109,9 &#177; 15,6 ms <italic>vs</italic> 99,5 &#177; 11,6 ms, p &lt; 0,001), maior dispers&#227;o da onda P (&#177; 37,9 <italic>vs</italic> 24,9 &#177; 3,4 ms 9,1 ms, p &lt; 0,001), di&#226;metro do &#225;trio esquerdo maior (42,9 &#177; 4,5 mil&#237;metros <italic>vs</italic> 30 &#177; 6,3 mil&#237;metros, p &lt; 0,001); 66 de 198 pacientes mostraram FTP <underline>&lt;</underline> -0,04 mm/s, enquanto todo o grupo de controle apresentou FTP &gt; -0,04 mm/s (p &lt; 0,0001).</p>
    <p>Todos os pacientes tiveram sucesso no isolamento das veias pulmonares e todos os pacientes estavam em ritmo sinusal ao final do procedimento. N&#227;o foi observada recorr&#234;ncia da FA durante as primeiras 24 horas ap&#243;s o procedimento de abla&#231;&#227;o. Durante um acompanhamento m&#233;dio de 9 &#177; 3 meses, recorr&#234;ncias ocorreram em 30,3% (60/198). As caracter&#237;sticas cl&#237;nicas do total de pacientes com FA parox&#237;stica e os dois grupos est&#227;o resumidas na <xref ref-type="table" rid="aop_5444tab01">tabela 1</xref>.</p>
    <p>Pacientes com recorr&#234;ncia de FA tiveram maior dura&#231;&#227;o m&#233;dia da onda P (122,9 &#177; 10,3 <italic>vs</italic> 104,3 &#177; 14,2 ms, p &lt; 0,001), maior dispers&#227;o da onda P (40,7 &#177; 1,7 ms <italic>vs</italic> 36,6 &#177; 3,2 ms, p &lt; 0,001), quando comparados com pacientes sem recorr&#234;ncia de fibrila&#231;&#227;o atrial (<xref ref-type="fig" rid="aop_5444fig02">Figuras 2</xref> e <xref ref-type="fig" rid="aop_5444fig03">3</xref>). Uma an&#225;lise mais profunda do subgrupo de pacientes com tamanho normal do AE mostrou que pacientes com tamanho normal do AE e recorr&#234;ncia de FA p&#243;s IVP apresentaram maior dura&#231;&#227;o da onda P (119,5 &#177; 13,5 ms versus 100,6 &#177; 11,38, p = 0,01) e maior dispers&#227;o da onda P (38,09 &#177; 2,7ms <italic>vs</italic> 35,86 &#177; 3,38, p = 0,03), em compara&#231;&#227;o com pacientes com tamanho normal do AE sem recorr&#234;ncia da FA.</p>
    <p content-type="asset">
      <fig id="aop_5444fig02">
        <graphic xlink:href="1678-4170-abc-101-06-0519-30214-gf02.jpg"/></fig>
    </p>
    <p content-type="asset">
      <fig id="aop_5444fig03">
        <graphic xlink:href="1678-4170-abc-101-06-0519-30214-gf03.jpg"/></fig>
    </p>
    <p>Quarenta e oito dos 66 (72,7%) pacientes com for&#231;a terminal de onda P <underline>&lt;</underline> -0,04 mm/s tiveram recorr&#234;ncia da FA, quando comparados com 12/132 (9%) pacientes com for&#231;a terminal de onda P &gt;- 0,04 mm/s (p &lt; 0,001). O eixo da onda P n&#227;o foi significativamente diferente entre pacientes com e sem recorr&#234;ncia de fibrila&#231;&#227;o atrial (p &gt; 0,09).</p>
    <p>A an&#225;lise das curvas caracter&#237;sticas de opera&#231;&#227;o do receptor (ROC) foi realizada para diferentes pontos de corte da dura&#231;&#227;o e dispers&#227;o da onda P (<xref ref-type="fig" rid="aop_5444fig04">Figuras 4</xref> e <xref ref-type="fig" rid="aop_5444fig05">5</xref>). A &#225;rea sob a curva ROC para a dura&#231;&#227;o da onda P foi de 0,858 (intervalo de confian&#231;a de 95% 0,805-0,912) ( p &lt; 0,001), a &#225;rea sob a curva ROC para a dispers&#227;o da onda P foi 0,852 (intervalo de confian&#231;a de 95% 0,8 - 0,904) (p &lt; 0,001). Observando-se os diferentes valores de corte, a dura&#231;&#227;o da onda P <underline>&gt;</underline> 125 ms e dispers&#227;o da onda P <underline>&gt;</underline> 40 ms diferenciaram os pacientes propensos &#224; recorr&#234;ncia de fibrila&#231;&#227;o atrial ao longo do tempo de acordo com o teste de log-rank (<xref ref-type="fig" rid="aop_5444fig06">Figuras 6</xref> e <xref ref-type="fig" rid="aop_5444fig07">7</xref>). A dura&#231;&#227;o de 125 ms da onda P tem a melhor sensibilidade e especificidade combinadas (60% e 90%, respectivamente), juntamente com valor preditivo positivo de 72% e valor preditivo negativo de 83,7%, enquanto a dispers&#227;o da onda P de 40 ms tem a melhor sensibilidade e especificidade combinadas (78% e 67%, respectivamente), juntamente com valor preditivo positivo de 51% e valor preditivo negativo de 87,6%.</p>
    <p content-type="asset">
      <fig id="aop_5444fig04">
        <graphic xlink:href="1678-4170-abc-101-06-0519-30214-gf04.jpg"/></fig>
    </p>
    <p content-type="asset">
      <fig id="aop_5444fig05">
        <graphic xlink:href="1678-4170-abc-101-06-0519-30214-gf05.jpg"/></fig>
    </p>
    <p content-type="asset">
      <fig id="aop_5444fig06">
        <graphic xlink:href="1678-4170-abc-101-06-0519-30214-gf06.jpg"/></fig>
    </p>
    <p content-type="asset">
      <fig id="aop_5444fig07">
        <graphic xlink:href="1678-4170-abc-101-06-0519-30214-gf07.jpg"/></fig>
    </p>
    <p>A an&#225;lise de regress&#227;o multivariada de Cox mostrou que os &#237;ndices da onda P n&#227;o eram independentes do tamanho do &#225;trio esquerdo e idade; por&#233;m, a dura&#231;&#227;o da onda P tem correla&#231;&#227;o moderada com a idade (r = 0,3, p &lt; 0,001), e boa correla&#231;&#227;o com o tamanho do &#225;trio esquerdo (r = 0,5, p &lt; 0,001). N&#227;o foi encontrada correla&#231;&#227;o significativa entre a dura&#231;&#227;o da onda P e o eixo da onda P (r = 0,03, p = 0,6). A dispers&#227;o da onda P teve correla&#231;&#227;o positiva moderada com a idade (r = 0,41, p &lt; 0,001) e volume do &#225;trio esquerdo (r = 0,42, p &lt; 0,001). A dura&#231;&#227;o da onda P e a dispers&#227;o da onda P tiveram uma correla&#231;&#227;o positiva moderada (r = 0,3, p &lt; 0,001).</p>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>A FA &#233; uma das arritmias mais importantes encontradas na &#225;rea da cardiologia, pois &#233; a mais comum e causa muitas complica&#231;&#245;es. V&#225;rias estrat&#233;gias t&#234;m sido utilizadas em seu tratamento e a import&#226;ncia da abla&#231;&#227;o da FA tem aumentado por se acreditar que pode curar a arritmia. O desafio da recorr&#234;ncia da fibrila&#231;&#227;o atrial ap&#243;s abla&#231;&#227;o ainda &#233; alto, de forma que nosso estudo prop&#245;e um preditor n&#227;o invasivo e facilmente aplic&#225;vel para a recorr&#234;ncia de FA, que s&#227;o os &#237;ndices da onda P obtidos pelo ECG padr&#227;o de 12 deriva&#231;&#245;es. </p>
    <p>V&#225;rios preditores independentes de recorr&#234;ncia de FA p&#243;s-abla&#231;&#227;o por RF foram identificados, tais como idade, FA persistente<sup>1</sup>, hipertens&#227;o, hiperlipidemia, di&#226;metro do &#225;trio esquerdo, contagem de c&#233;lulas brancas do sangue antes da abla&#231;&#227;o<sup>2,3</sup> e remodelamento atrial por RM com contraste tardio<sup>4</sup>, embora marcadores quantitativos n&#227;o invasivos ainda sejam necess&#225;rios.</p>
    <p>A dura&#231;&#227;o prolongada da onda P denota condu&#231;&#227;o anormal inter e intra-atrial. Dogan e cols.<sup>9</sup> relataram que a m&#225;xima dura&#231;&#227;o e dispers&#227;o da onda P eram preditores da manuten&#231;&#227;o do ritmo sinusal ap&#243;s cardiovers&#227;o da FA e que o aumento da dispers&#227;o da onda P poderia ser usado para identificar pacientes em risco de recorr&#234;ncia ap&#243;s esse procedimento.</p>
    <p>Estudos anteriores foram feitos para avaliar diferentes valores de dura&#231;&#227;o e dispers&#227;o da onda P para prever a ocorr&#234;ncia de fibrila&#231;&#227;o atrial p&#243;s-cardiovers&#227;o, p&#243;s-infarto do mioc&#225;rdio e tamb&#233;m ap&#243;s cirurgia card&#237;aca. Rosiak e cols.<sup>10</sup> demonstraram que a dura&#231;&#227;o da onda P &gt; 125 ms e dispers&#227;o da onda P &gt; 25 ms, quando medidas logo ap&#243;s o infarto agudo do mioc&#225;rdio, eram independentemente associadas com a FA.</p>
    <p>A rela&#231;&#227;o entre a dura&#231;&#227;o da onda P e o atraso eletromec&#226;nico atrial foi avaliada atrav&#233;s de ecocardiograma com Doppler tecidual por Dabrowska-Kugacka e cols.<sup>11</sup>, que conclu&#237;ram que a dura&#231;&#227;o do ECG de superf&#237;cie &#233; altamente correlacionada com o atraso eletromec&#226;nico e, a partir dessa rela&#231;&#227;o, pode-se verificar a import&#226;ncia da dura&#231;&#227;o da onda P no ECG de superf&#237;cie como preditor da recorr&#234;ncia da fibrila&#231;&#227;o atrial ap&#243;s isolamento da veia pulmonar.</p>
    <p>Outros estudos que usaram a m&#233;dia do sinal de onda P para prever recorr&#234;ncia da fibrila&#231;&#227;o atrial ap&#243;s isolamento das veias pulmonares conclu&#237;ram que a dura&#231;&#227;o da onda P filtrada &gt; 140 ms no eletrocardiograma de alta resolu&#231;&#227;o da onda P &#233; um marcador &#250;til de recorr&#234;ncia de FA ao longo do tempo ap&#243;s isolamento das veias pulmonares. Embora esta t&#233;cnica ainda n&#227;o seja amplamente utilizada, ela confirma que a dura&#231;&#227;o prolongada provavelmente reflete os atrasos de condu&#231;&#227;o inter e/ou intra-atrial e pode estar relacionada com a extens&#227;o das cicatrizes e fibrose atrial, como demonstrado pela maior dura&#231;&#227;o da onda P em pacientes com FA recorrente<sup>12</sup>.</p>
    <p>A morfologia da onda P representa a ativa&#231;&#227;o el&#233;trica atrial que depende principalmente da dist&#226;ncia percorrida pela corrente el&#233;trica, a partir do primeiro ponto de despolariza&#231;&#227;o at&#233; o &#250;ltimo ponto de despolariza&#231;&#227;o, juntamente com a velocidade da corrente el&#233;trica. O remodelamento atrial, que &#233; o principal substrato da FA, &#233; essencialmente dividido em remodelamento estrutural e el&#233;trico, sendo que na maioria dos casos ambos ir&#227;o ocorrer em conjunto. O remodelamento estrutural &#233; representado principalmente pelo aumento dos &#225;trios detectado pelo ecocardiograma, enquanto o remodelamento el&#233;trico &#233; representado pelo prolongamento do tempo eletromec&#226;nico, demonstrado pelo Doppler tecidual ou de forma invasiva medindo o tempo total de ativa&#231;&#227;o atrial entre o primeiro potencial atrial detectado pelo eletrodo intracard&#237;aco, posicionado no &#225;trio direito alto, e o &#250;ltimo potencial atrial detectado pelo eletrodo intracard&#237;aco posicionado no seio coron&#225;rio distal. As principais caracter&#237;sticas do processo de remodela&#231;&#227;o el&#233;ctrica s&#227;o a redu&#231;&#227;o do per&#237;odo refrat&#225;rio com o aumento da dispers&#227;o e a redu&#231;&#227;o da condutividade atrial. A partir deste ponto sobre a remodela&#231;&#227;o atrial el&#233;trica, podemos esclarecer nossas conclus&#245;es em rela&#231;&#227;o aos pacientes com tamanho normal do AE, pois verificamos que, mesmo em pacientes com tamanho normal do AE, pacientes com recorr&#234;ncia de FA ap&#243;s IVP apresentaram dura&#231;&#227;o da onda P e dispers&#227;o da onda P mais longas, em compara&#231;&#227;o com pacientes com tamanho do AE normal sem recorr&#234;ncia de FA.</p>
    <p>As recorr&#234;ncias de FA ap&#243;s IVP ocorrem principalmente devido &#224; recondu&#231;&#227;o da VP no mioc&#225;rdio ablacionado ou algumas vezes em focos n&#227;o-VP<sup>13-16</sup>. Para testar a hip&#243;tese de que a dura&#231;&#227;o da onda P pode ser um marcador de um IVP bem sucedido, Date e cols.<sup>17</sup> estudaram o contribui&#231;&#227;o dos m&#250;sculos card&#237;acos da VP para a onda P usando um vetorcardiograma padr&#227;o e eletrocardiograma gravado antes e ap&#243;s o procedimento. Eles verificaram que a morfologia da onda P mudou depois do IVP e que o <italic>sleeve</italic> mioc&#225;rdico da VP desempenhava um papel importante na forma&#231;&#227;o da parte do meio da onda P.</p>
    <p>A dispers&#227;o da onda P ainda est&#225; em estudo e n&#227;o se sabe se a mesma &#233; determinada apenas pela heterogeneidade de condu&#231;&#227;o atrial ou por outros fatores<sup>18, 19</sup>. Em nosso estudo, verificamos que a dura&#231;&#227;o da onda P <underline>&gt;</underline> 125 ms e o valor de dispers&#227;o da onda P de <underline>&gt;</underline> 40 ms est&#227;o associados com maior taxa de recorr&#234;ncia de FA ap&#243;s IVP em pacientes com fibrila&#231;&#227;o atrial parox&#237;stica.</p>
    <p>Uma grande for&#231;a terminal da onda P na deriva&#231;&#227;o V1 junto com uma dura&#231;&#227;o da onda P prolongada prev&#234; anormalidade atrial esquerda, particularmente em pacientes com doen&#231;a cardiovascular subjacente (sensibilidade 82%, especificidade, de 40%, valor preditivo positivo de 70% e valor preditivo negativo de 55%), e sua presen&#231;a indica a necessidade de avalia&#231;&#245;es adicionais<sup>20</sup>. Al&#233;m disso, a for&#231;a terminal da onda P na deriva&#231;&#227;o V1 foi independentemente associada com AVC isqu&#234;mico ap&#243;s ajuste para outros fatores de risco para acidente vascular cerebral (<italic>odds ratio</italic>, 2,32, intervalo de confian&#231;a de 95%, 1,29-4,18)<sup>21</sup>.</p>
    <p>A maior preval&#234;ncia de FTPV1 <underline>&lt;</underline> -0,04 mm/s em pacientes com dura&#231;&#227;o prolongada da onda P e dispers&#227;o da onda P mais ampla, como observado em nosso estudo, provavelmente reflete a condu&#231;&#227;o do impulso tardio associado com um &#225;trio esquerdo anormal e aumentado.</p>
    <p>
      <bold>Implica&#231;&#227;o cl&#237;nica</bold>
    </p>
    <p>Nossos resultados indicam que a dura&#231;&#227;o da onda P, a dispers&#227;o da onda P, juntamente com a for&#231;a terminal da onda P em V1 podem ser marcadores &#250;teis de recorr&#234;ncia de FA ap&#243;s IVP, provavelmente refletindo a extens&#227;o da doen&#231;a atrial e remodelamento.</p>
    <p>
      <bold>Limita&#231;&#227;o do Estudo</bold>
    </p>
    <p>A terapia com drogas antiarr&#237;tmicas pr&#233;-abla&#231;&#227;o n&#227;o foi descontinuada antes da abla&#231;&#227;o com cateter por radiofrequ&#234;ncia; drogas como amiodarona e flecainida podem ter influenciado a recorr&#234;ncia. A dura&#231;&#227;o dos dados da FA foi obtida a partir do hist&#243;rico do paciente e registros de ECG; assim, a exist&#234;ncia de portadores assintom&#225;ticos de FA n&#227;o pode ser exclu&#237;da e a dura&#231;&#227;o da FA pode n&#227;o ser exata. Os epis&#243;dios assintom&#225;ticos de AF tamb&#233;m podem confundir os resultados de recorr&#234;ncia de FA durante o acompanhamento. O tamanho da amostra &#233; relativamente pequeno e os resultados do presente estudo devem ser confirmados por estudos prospectivos maiores.</p>
    <p>
      <bold>Conclus&#227;o</bold>
    </p>
    <p>A dura&#231;&#227;o da onda P <underline>&gt;</underline> 125ms, dispers&#227;o da onda P <underline>&gt;</underline> 40ms, bem como a for&#231;a terminal da onda P em V1 <underline>&lt;</underline> -0.04 mm/s s&#227;o bons preditores cl&#237;nicos de sequelas delet&#233;rias j&#225; conhecidas, principalmente recorr&#234;ncia de fibrila&#231;&#227;o atrial ap&#243;s IVP em pacientes com fibrila&#231;&#227;o atrial parox&#237;stica; no entanto elas n&#227;o foram independentes do tamanho do &#225;trio esquerdo e idade.</p>
    <p>
      <bold>Contribui&#231;&#227;o dos autores</bold>
    </p>
    <p>Concep&#231;&#227;o e desenho da pesquisa: Salah A, Zhou S. Obten&#231;&#227;o de dados: Salah A, Zhou S, Liu Q, Yang H. An&#225;lise e interpreta&#231;&#227;o dos dados: Salah A, Zhou S, Liu Q, Yang H. An&#225;lise estat&#237;stica: Salah A, Zhou S, Yang H. Reda&#231;&#227;o do manuscrito: Salah A, Yang H. Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual: Salah A, Zhou S, Liu Q, Yang H. Supervis&#227;o / como investigador principal: Salah A, Zhou S. Realiza&#231;&#227;o de isolamento das veias pulmonares em EP Lab. cateter: Salah A, Liu Q.</p>
    <p>
      <bold>Potencial Conflito de Interesses</bold>
    </p>
    <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
    <p>
      <bold>Fontes de Financiamento</bold>
    </p>
    <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
    <p>
      <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
    </p>
    <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
    <p>
      <fn id="end" fn-type="corresp">
        <p>Correspond&#234;ncia:</p>
        <p> Shenghua Zhou </p>
        <p> Departamento de Cardiologia, The Second Xiangya Hospital of Central South University </p>
        <p> middle Ren-Min road, 139, Changsha </p>
        <p> C&#243;digo Postal 410011, Hunan, China </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="zhougqin@21cn.com">zhougqin@21cn.com</email>
        </p>
      </fn>
    </p>
    <p>Artigo recebido em 19/02/13; revisado em 29/07/13, aceito em 05/08/13.</p>
  </body>
  <back>
    <ref-list>
      <ref id="B1">
        <mixed-citation>1. Tzou WS, Marchlinski FE, Zado ES, Lin D, Dixit S, Callans DJ, et al. Long-term outcome after successful catheter ablation of atrial fibrillation. Circ Arrhythm Electrophysiol. 2010;3(3):237-42.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Long-term outcome after successful catheter ablation of atrial fibrillation</article-title>
          <source>Circ Arrhythm Electrophysiol</source>
          <date>
            <year>2010</year>
          </date>
          <fpage>237</fpage>
          <lpage>42</lpage>
          <issue>3</issue>
          <volume>3</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Tzou</surname>
              <given-names>WS</given-names>
            </name>
            <name>
              <surname>Marchlinski</surname>
              <given-names>FE</given-names>
            </name>
            <name>
              <surname>Zado</surname>
              <given-names>ES</given-names>
            </name>
            <name>
              <surname>Lin</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Dixit</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Callans</surname>
              <given-names>DJ</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B2">
        <mixed-citation>2. Letsas KP, Weber R, B&#252;rkle G, Mihas CC, Minners J, Kalusche D, et al. Pre-ablative predictors of atrial fibrillation recurrence following pulmonary vein isolation: the potential role of inflammation. Europace. 2009;11(2):158-63.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Pre-ablative predictors of atrial fibrillation recurrence following pulmonary vein isolation: the potential role of inflammation</article-title>
          <source>Europace</source>
          <date>
            <year>2009</year>
          </date>
          <fpage>158</fpage>
          <lpage>63</lpage>
          <issue>2</issue>
          <volume>11</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Letsas</surname>
              <given-names>KP</given-names>
            </name>
            <name>
              <surname>Weber</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>B&#252;rkle</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Mihas</surname>
              <given-names>CC</given-names>
            </name>
            <name>
              <surname>Minners</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Kalusche</surname>
              <given-names>D</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B3">
        <mixed-citation>3. Shah AN, Mittal S, Sichrovsky TC, Cotiga D, Arshad A, Maleki K, et al. . Long-term outcome following successful pulmonary vein isolation: pattern and prediction of very late recurrence. J Cardiovasc Electrophysiol. 2008;19(7):661-7.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Long-term outcome following successful pulmonary vein isolation: pattern and prediction of very late recurrence</article-title>
          <source>J Cardiovasc Electrophysiol</source>
          <date>
            <year>2008</year>
          </date>
          <fpage>661</fpage>
          <lpage>7</lpage>
          <issue>7</issue>
          <volume>19</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Shah</surname>
              <given-names>AN</given-names>
            </name>
            <name>
              <surname>Mittal</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Sichrovsky</surname>
              <given-names>TC</given-names>
            </name>
            <name>
              <surname>Cotiga</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Arshad</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Maleki</surname>
              <given-names>K</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B4">
        <mixed-citation>4. Oakes RS, Badger TJ, Kholmovski EG, Akoum N, Burgon NS, Fish EN, et al. Detection and quantification of left atrial structural remodeling with delayed-enhancement magnetic resonance imaging in patients with atrial fibrillation. Circulation. 2009;119(13):1758-67.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Detection and quantification of left atrial structural remodeling with delayed-enhancement magnetic resonance imaging in patients with atrial fibrillation</article-title>
          <source>Circulation</source>
          <date>
            <year>2009</year>
          </date>
          <fpage>1758</fpage>
          <lpage>67</lpage>
          <issue>13</issue>
          <volume>119</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Oakes</surname>
              <given-names>RS</given-names>
            </name>
            <name>
              <surname>Badger</surname>
              <given-names>TJ</given-names>
            </name>
            <name>
              <surname>Kholmovski</surname>
              <given-names>EG</given-names>
            </name>
            <name>
              <surname>Akoum</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Burgon</surname>
              <given-names>NS</given-names>
            </name>
            <name>
              <surname>Fish</surname>
              <given-names>EN</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B5">
        <mixed-citation>5. Carnes CA, Chung MK, Nakayama T, Nakayama H, Baliga RS, Pia OS, et al. Ascorbate attenuates atrial pacing-induced peroxynitrite formation and electrical remodeling and decreases the incidence of postoperative atrial fibrillation. Circ Res. 2001;89(6):E32-8.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Ascorbate attenuates atrial pacing-induced peroxynitrite formation and electrical remodeling and decreases the incidence of postoperative atrial fibrillation</article-title>
          <source>Circ Res</source>
          <date>
            <year>2001</year>
          </date>
          <fpage>E32</fpage>
          <lpage>8</lpage>
          <issue>6</issue>
          <volume>89</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Carnes</surname>
              <given-names>CA</given-names>
            </name>
            <name>
              <surname>Chung</surname>
              <given-names>MK</given-names>
            </name>
            <name>
              <surname>Nakayama</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Nakayama</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Baliga</surname>
              <given-names>RS</given-names>
            </name>
            <name>
              <surname>Pia</surname>
              <given-names>OS</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B6">
        <mixed-citation>6. Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, et al; European Heart Rhythm Association; European Association for Cardio-Thoracic Surgery. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Europace. 2010;12(10):1360-420. Erratum in: Europace. 2011;13(7):1058.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC)</article-title>
          <source>Europace</source>
          <date>
            <year>2010</year>
          </date>
          <fpage>1360</fpage>
          <lpage>420</lpage>
          <issue>10</issue>
          <volume>12</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Camm</surname>
              <given-names>AJ</given-names>
            </name>
            <name>
              <surname>Kirchhof</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Lip</surname>
              <given-names>GY</given-names>
            </name>
            <name>
              <surname>Schotten</surname>
              <given-names>U</given-names>
            </name>
            <name>
              <surname>Savelieva</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Ernst</surname>
              <given-names>S</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B7">
        <mixed-citation>7. Dilaveris P, Batchvarov V, Gialafos J, Malik M. Comparison of different methods for manual P wave duration measurement in 12-lead electrocardiograms. Pacing Clin Electrophysiol. 1999;22(10):1532-8.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Comparison of different methods for manual P wave duration measurement in 12-lead electrocardiograms</article-title>
          <source>Pacing Clin Electrophysiol</source>
          <date>
            <year>1999</year>
          </date>
          <fpage>1532</fpage>
          <lpage>8</lpage>
          <issue>10</issue>
          <volume>22</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Dilaveris</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Batchvarov</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Gialafos</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Malik</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B8">
        <mixed-citation>8. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986;1(8476):307-10.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Statistical methods for assessing agreement between two methods of clinical measurement</article-title>
          <source>Lancet</source>
          <date>
            <year>1986</year>
          </date>
          <fpage>307</fpage>
          <lpage>10</lpage>
          <issue>8476</issue>
          <volume>1</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Bland</surname>
              <given-names>JM</given-names>
            </name>
            <name>
              <surname>Altman</surname>
              <given-names>DG</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B9">
        <mixed-citation>9. Dogan A, Kahraman H, Ozturk M, Avsar A. P wave dispersion and left atrial appendage function for predicting recurrence after conversion of atrial fibrillation and relation of p wave dispersion to appendage function. Echocardiography. 2004;21(6):523-30.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>P wave dispersion and left atrial appendage function for predicting recurrence after conversion of atrial fibrillation and relation of p wave dispersion to appendage function</article-title>
          <source>Echocardiography</source>
          <date>
            <year>2004</year>
          </date>
          <fpage>523</fpage>
          <lpage>30</lpage>
          <issue>6</issue>
          <volume>21</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Dogan</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Kahraman</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Ozturk</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Avsar</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B10">
        <mixed-citation>10. Rosiak M, Bolinska H, Ruta J. P wave dispersion and P wave duration on SAECG in predicting atrial fibrillation in patients with acute myocardial infarction. Ann Noninvasive Electrocardiol. 2002;7(4):363-8.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>P wave dispersion and P wave duration on SAECG in predicting atrial fibrillation in patients with acute myocardial infarction</article-title>
          <source>Ann Noninvasive Electrocardiol</source>
          <date>
            <year>2002</year>
          </date>
          <fpage>363</fpage>
          <lpage>8</lpage>
          <issue>4</issue>
          <volume>7</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Rosiak</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Bolinska</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Ruta</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B11">
        <mixed-citation>11. Dabrowska-Kugacka A, Lewicka-Nowak E, Ruciaski P, Zagozdzon P, Rackzak G, Kutarski A. Relationship between P-wave duration and atrial electromechanical delay assessed by tissue Doppler echocardiography. Pacing Clin Electrophysiol. 2011;34(1):23-31.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Relationship between P-wave duration and atrial electromechanical delay assessed by tissue Doppler echocardiography</article-title>
          <source>Pacing Clin Electrophysiol</source>
          <date>
            <year>2011</year>
          </date>
          <fpage>23</fpage>
          <lpage>31</lpage>
          <issue>1</issue>
          <volume>34</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Dabrowska-Kugacka</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Lewicka-Nowak</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Ruciaski</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Zagozdzon</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Rackzak</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Kutarski</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B12">
        <mixed-citation>12. Blanche C, Tran N, Rigamonti F, Burri H, Zimmermann M. Value of P-wave signal averaging to predict atrial fibrillation recurrences after pulmonary vein isolation. Europace. 2012;15(2):198-204.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Value of P-wave signal averaging to predict atrial fibrillation recurrences after pulmonary vein isolation</article-title>
          <source>Europace</source>
          <date>
            <year>2012</year>
          </date>
          <fpage>198</fpage>
          <lpage>204</lpage>
          <issue>2</issue>
          <volume>15</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Blanche</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Tran</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Rigamonti</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Burri</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Zimmermann</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B13">
        <mixed-citation>13. Ouyang F, Antz M, Ernst S, Hachiya H, Mavrakis H, Deger FT, et al. Recovered pulmonary vein conduction as a dominant factor for recurrent atrial tachyarrhythmias after complete circular isolation of the pulmonary veins: lessons from double Lasso technique. Circulation. 2005;111(2):127-35.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Recovered pulmonary vein conduction as a dominant factor for recurrent atrial tachyarrhythmias after complete circular isolation of the pulmonary veins: lessons from double Lasso technique</article-title>
          <source>Circulation</source>
          <date>
            <year>2005</year>
          </date>
          <fpage>127</fpage>
          <lpage>35</lpage>
          <issue>2</issue>
          <volume>111</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Ouyang</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Antz</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Ernst</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Hachiya</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Mavrakis</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Deger</surname>
              <given-names>FT</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B14">
        <mixed-citation>14. Gerstenfeld EP, Callans DJ, Dixit S, Zado E, Marchlinski FE. Incidence and location of focal atrial fibrillation triggers in patients undergoing repeat pulmonary vein isolation: implications for ablation strategies. J Cardiovasc Electrophysiol. 2003;14(7):685-90.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Incidence and location of focal atrial fibrillation triggers in patients undergoing repeat pulmonary vein isolation: implications for ablation strategies</article-title>
          <source>J Cardiovasc Electrophysiol</source>
          <date>
            <year>2003</year>
          </date>
          <fpage>685</fpage>
          <lpage>90</lpage>
          <issue>7</issue>
          <volume>14</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Gerstenfeld</surname>
              <given-names>EP</given-names>
            </name>
            <name>
              <surname>Callans</surname>
              <given-names>DJ</given-names>
            </name>
            <name>
              <surname>Dixit</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Zado</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Marchlinski</surname>
              <given-names>FE</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B15">
        <mixed-citation>15. Nanthakumar K, Plumb VJ, Epstein AE, Veenhuyzen GD, Link D, et al. Resumption of electrical conduction in previously isolated pulmonary veins: rationale for a different strategy. Circulation. 2004;109(10):1226-9.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Resumption of electrical conduction in previously isolated pulmonary veins: rationale for a different strategy</article-title>
          <source>Circulation</source>
          <date>
            <year>2004</year>
          </date>
          <fpage>1226</fpage>
          <lpage>9</lpage>
          <issue>10</issue>
          <volume>109</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Nanthakumar</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Plumb</surname>
              <given-names>VJ</given-names>
            </name>
            <name>
              <surname>Epstein</surname>
              <given-names>AE</given-names>
            </name>
            <name>
              <surname>Veenhuyzen</surname>
              <given-names>GD</given-names>
            </name>
            <name>
              <surname>Link</surname>
              <given-names>D</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B16">
        <mixed-citation>16. Verma A, Kilicaslan F, Pisano E, Marrouche NF, Fanelli R, Brachmann J, et al. Response of atrial fibrillation to pulmonary vein antrum isolation is directly related to resumption and delay of pulmonary vein conduction. Circulation. 2005;112(5):627-35.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Response of atrial fibrillation to pulmonary vein antrum isolation is directly related to resumption and delay of pulmonary vein conduction</article-title>
          <source>Circulation</source>
          <date>
            <year>2005</year>
          </date>
          <fpage>627</fpage>
          <lpage>35</lpage>
          <issue>5</issue>
          <volume>112</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Verma</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Kilicaslan</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Pisano</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Marrouche</surname>
              <given-names>NF</given-names>
            </name>
            <name>
              <surname>Fanelli</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Brachmann</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B17">
        <mixed-citation>17. Date T, Yamane T, Inada K, Matsuo S, Kanzaki Y, Miynaga S, et al. The effects of pulmonary vein isolation on the morphology of P-waves: the contribution of pulmonary vein muscle excitation to the formation of P-waves. Pacing Clin Electrophysiol. 2007;30(1):93-101.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>The effects of pulmonary vein isolation on the morphology of P-waves: the contribution of pulmonary vein muscle excitation to the formation of P-waves</article-title>
          <source>Pacing Clin Electrophysiol</source>
          <date>
            <year>2007</year>
          </date>
          <fpage>93</fpage>
          <lpage>101</lpage>
          <issue>1</issue>
          <volume>30</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Date</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Yamane</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Inada</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Matsuo</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Kanzaki</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Miynaga</surname>
              <given-names>S</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B18">
        <mixed-citation>18. Nussinovitch N, Livneh A, Katz K, Nussinovitch M, Volovitz B, Lidar M, et al. P wave dispersion in familial Mediterranean fever. Rheumatol Int. 2011;31(12):1591-4.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>P wave dispersion in familial Mediterranean fever</article-title>
          <source>Rheumatol Int</source>
          <date>
            <year>2011</year>
          </date>
          <fpage>1591</fpage>
          <lpage>4</lpage>
          <issue>12</issue>
          <volume>31</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Nussinovitch</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Livneh</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Katz</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Nussinovitch</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Volovitz</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Lidar</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B19">
        <mixed-citation>19. Michelucci A, Bagliani G, Colella A, Pieragnoli P, Porciani MC, Gensini G, et al. P wave assessment: state of the art update. Card Electrophysiol Rev. 2002;6(3):215-20.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>P wave assessment: state of the art update</article-title>
          <source>Card Electrophysiol Rev</source>
          <date>
            <year>2002</year>
          </date>
          <fpage>215</fpage>
          <lpage>20</lpage>
          <issue>3</issue>
          <volume>6</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Michelucci</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Bagliani</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Colella</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Pieragnoli</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Porciani</surname>
              <given-names>MC</given-names>
            </name>
            <name>
              <surname>Gensini</surname>
              <given-names>G</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B20">
        <mixed-citation>20. Jin L, Weisse AB, Hernandez F, Jordan T. Significance of electrocardiographic  isolated abnormal terminal P-wave force (left atrial abnormality): an echocardiographic and clinical correlation. Arch Intern Med. 1988;148(7):1545-9.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Significance of electrocardiographic isolated abnormal terminal P-wave force (left atrial abnormality): an echocardiographic and clinical correlation</article-title>
          <source>Arch Intern Med</source>
          <date>
            <year>1988</year>
          </date>
          <fpage>1545</fpage>
          <lpage>9</lpage>
          <issue>7</issue>
          <volume>148</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Jin</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Weisse</surname>
              <given-names>AB</given-names>
            </name>
            <name>
              <surname>Hernandez</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Jordan</surname>
              <given-names>T</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B21">
        <mixed-citation>21. Kohsaka S, Sciacca RR, Sugioka K, Sacco RL, Homma S, Di Tullio MR. Electrocardiographic left atrial abnorm alities and risk of ischemic stroke. Stroke. 2005;36(11):2481-3.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Electrocardiographic left atrial abnorm alities and risk of ischemic stroke</article-title>
          <source>Stroke</source>
          <date>
            <year>2005</year>
          </date>
          <fpage>2481</fpage>
          <lpage>3</lpage>
          <issue>11</issue>
          <volume>36</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Kohsaka</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Sciacca</surname>
              <given-names>RR</given-names>
            </name>
            <name>
              <surname>Sugioka</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Sacco</surname>
              <given-names>RL</given-names>
            </name>
            <name>
              <surname>Homma</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Di Tullio</surname>
              <given-names>MR</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
    </ref-list>
  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">P wave indices to predict atrial fibrillation recurrences post pulmonary vein isolation</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>BACKGROUND: P-wave indices are appealing markers for predicting atrial fibrillation (AF) recurrences post ablation. OBJECTIVE: This study evaluates the value of P wave indices to predict recurrences post pulmonary vein isolation (PVI) in patients with paroxysmal AF. METHODS: We selected 198 patients (57 &#177; 8 years, 150 males) with symptomatic drug-refractory paroxysmal AF undergoing PVI in our hospital. A 12-lead electrocardiogram was used to measure P wave duration in lead II, P wave terminal force (PWTF) in lead V1, P wave axis and dispersion. RESULTS: During a follow-up of 9 &#177; 3 months, recurrences occurred in 60 (30.3%) patients. The patients that had AF recurrence had longer mean P wave duration (122.9 &#177; 10.3 vs 104.3 &#177; 14.2 ms, p &lt; 0.001), larger P wave dispersion (40.7 &#177; 1.7 ms vs 36.6 &#177; 3.2 ms, p &lt; 0.001). P wave duration &gt; 125 ms has 60% sensitivity, 90% specificity, positive predictive value (PPV) of 72% and negative predictive value (NPV) of 83.7%, whereas P wave dispersion &gt; 40 ms has 78% sensitivity, 67% specificity, PPV of 51% and NPV of 87.6% 48/66 (72.7%) patients with PWTF &lt; -0.04 mm/second vs12/132(9%) with PWTF &gt; -0.04 mm/second showed recurrence of AF (p &lt; 0.001). P wave axis was not different between two groups. On multivariate analysis, P wave indices were not independent from left atrial size and age. CONCLUSIONS: P wave duration &gt; 125 ms, P wave dispersion &gt; 40 ms and PWTF in V1 &lt; -0.04 mm/sec are good clinical predictors of AF recurrences post PVI in patients with paroxysmal atrial fibrillation; however they were not independent from left atrial size and age.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Atrial Fibrillation</kwd>
        <kwd>P Wave</kwd>
        <kwd>Ventricular Fibrillation</kwd>
        <kwd>Pulmonary Veins</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <fn id="enda-body2">
          <label>
            <bold>P Wave indices to predict atrial fibrillation recurrences post pulmonary vein isolation</bold>
          </label>
          <p>
            <bold>Ahmed Salah; Shenghua Zhou; Qiming Liu; Hui Yan</bold>
          </p>
        </fn>
      </p>
      <p>Second Xiangya Hospital of Central South University - China</p>
      <p>Mailing Address</p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p><bold>BACKGROUND:</bold> P-wave indices are appealing markers for predicting atrial fibrillation (AF) recurrences post ablation.</p>
      <p><bold>OBJECTIVE:</bold> This study evaluates the value of P wave indices to predict recurrences post pulmonary vein isolation (PVI) in patients with paroxysmal AF.</p>
      <p><bold>METHODS:</bold> We selected 198 patients (57 &#177; 8 years, 150 males) with symptomatic drug-refractory paroxysmal AF undergoing PVI in our hospital. A 12-lead electrocardiogram was used to measure P wave duration in lead II, P wave terminal force (PWTF) in lead V1, P wave axis and dispersion.</p>
      <p><bold>RESULTS:</bold> During a follow-up of 9 &#177; 3 months, recurrences occurred in 60 (30.3%) patients. The patients that had AF recurrence had longer mean P wave duration (122.9 &#177; 10.3 vs 104.3 &#177; 14.2 ms, p &lt; 0.001), larger P wave dispersion (40.7 &#177; 1.7 ms vs 36.6 &#177; 3.2 ms, p &lt; 0.001). P wave duration <underline>&gt;</underline> 125 ms has 60% sensitivity, 90% specificity, positive predictive value (PPV) of 72% and negative predictive value (NPV) of 83.7%, whereas P wave dispersion <underline>&gt;</underline> 40 ms has 78% sensitivity, 67% specificity, PPV of 51% and NPV of 87.6% 48/66 (72.7%) patients with PWTF <underline>&lt;</underline> -0.04 mm/second vs12/132(9%) with PWTF &gt; -0.04 mm/second showed recurrence of AF (p &lt; 0.001). P wave axis was not different between two groups. On multivariate analysis, P wave indices were not independent from left atrial size and age.</p>
      <p><bold>CONCLUSIONS:</bold> P wave duration <underline>&gt;</underline> 125 ms, P wave dispersion <underline>&gt;</underline> 40 ms and PWTF in V1 <underline>&lt;</underline> -0.04 mm/sec are good clinical predictors of AF recurrences post PVI in patients with paroxysmal atrial fibrillation; however they were not independent from left atrial size and age. </p>
      <p><bold>Keywords:</bold> Atrial Fibrillation; P Wave; Ventricular Fibrillation; Pulmonary Veins.</p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p>Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, of which importance derives from the fact that it is one of the most common leading causes of circulatory instability and stroke. The main goals in the management of AF are heart rate or rhythm control and anticoagulation. If rhythm control is desired and cannot be maintained by medication or cardioversion, then catheter ablation may be attempted.</p>
      <p>Radiofrequency catheter ablation (RFCA) of AF is effective in 70-80% of the cases, but recurrences are frequent and at the present time, accurate markers of recurrences are lacking<sup>1-4</sup>. The natural history of AF is characterized by self-perpetuating mechanisms, rate-induced electrophysiological changes and structural remodeling that involves the atrial myocardium<sup>5</sup>.</p>
      <p>Atrial remodeling is both electrical and structural; it causes slow electrical conduction and enlargement of the atria, which is reflected by changes in the morphology of the P wave in the electrocardiogram (ECG). Predictors to discriminate who will benefit from ablation are needed to save money, time and effort. Using ECG parameters as a predictor is very useful, as it is low-cost, feasible and can yield a lot of information. In our study we evaluated the use of P-wave indices to predict the recurrence of atrial fibrillation post pulmonary vein isolation (PVI) in patients with paroxysmal atrial fibrillation.</p>
      <p>
        <bold>Methods</bold>
      </p>
      <p>
        <bold>Population</bold>
      </p>
      <p>After informed consent, 198 consecutive patients (57 &#177; 8 years, 150 males, and 48 females) with symptomatic drug-refractory paroxysmal AF, undergoing RFCA were enrolled in our study. AF was classified as paroxysmal when episodes were generally self-terminating and lasted no longer than 7 days, according to the European Society of Cardiology guidelines<sup>6</sup>.</p>
      <p>Prior to the procedure, all patients underwent a comprehensive transthoracic echocardiographic examination to assess left atrial (LA) size and function, left ventricular (LV) function and to exclude structural heart disease; additionally, all patients underwent transesophageal echocardiography immediately before the ablation procedure to exclude LA thrombi. Clinical characteristics are summarized in <xref ref-type="table" rid="en_aop_5444tab01-body2">Table 1</xref>.</p>
      <p content-type="asset">
        <table-wrap id="en_aop_5444tab01-body2">
          <graphic xlink:href="1678-4170-abc-101-06-0519-30214-gt01-en.jpg"/></table-wrap>
      </p>
      <p>
        <bold>Standard 12 Lead Electrocardiogram (ECG)</bold>
      </p>
      <p>Standard 12 lead ECG was performed in all patients during sinus rhythm just before the ablation procedure using commercially available equipment (MAC 1200 ST General Electric Medical Information Technology). The ECG recorded before ablation procedure was the one used for statistical analysis, while another ECG recorded after ablation was used to confirm that the patient was in sinus rhythm post-procedure. Before ablation ECGs were recorded for 10 seconds first at a sweep speed of 25 mm/s and calibrated to 1 mV/cm in the standard leads and then at a sweep speed of 50 mm/s and calibrated to 2 mV/cm in the standard leads to obtain further precise measurements. Scanning and digitizing of ECG signals from paper records using an optical scanner were performed for all ECG recordings; the onset and offset of the P wave were defined as the start of the upward deflection of the P-wave pattern and its return to the isoelectric baseline in lead II<sup>7</sup>. All the following parameters were assessed; P-wave duration in lead II, P wave terminal force (PWTF) in lead V1, P wave axis and dispersion.</p>
      <p>P-wave dispersion was measured manually by subtracting the minimal P wave (Pmin) duration from the maximal P wave (Pmax) duration (Pmax - Pmin), measured by multiple surface ECG leads, from a single beat and mean values for three complexes were calculated.</p>
      <p>Calculation of the PWTF was performed by measuring the P wave duration in seconds multiplied by the P wave amplitude of the negative terminal portion of the P wave in V1 in millimeters as shown in <xref ref-type="fig" rid="en_aop_5444fig01-body2">Figure 1</xref>. The patients were further divided in to two groups, the first group in which the PWTF was &gt; -0.04 mm/sec. (smaller than one small square) and the second group in which the PWTF was <underline>&lt;</underline> -0.04 mm/sec. (larger than one small square).</p>
      <p content-type="asset">
        <fig id="en_aop_5444fig01-body2">
          <graphic xlink:href="1678-4170-abc-101-06-0519-30214-gf01-en.jpg"/></fig>
      </p>
      <p>A control group including 120 normal subjects (80 males; 40 females; mean age 44 &#177; 17 years) without any history of AF, structural heart disease or hypertension was used to define normal values for P-wave characteristics.</p>
      <p>After the ablation, all patients were systematically evaluated at the outpatient clinic during a mean follow up of 9 &#177; 3 months. ECG recordings were acquired on each visit and 24-h Holter recordings were scheduled after 3, 6 and 9 months of follow-up. Importantly, all patients were encouraged to immediately obtain an ECG registration when experiencing palpitations. Antiarrhythmic medications were interrupted after the ablation procedure and AF recurrence was defined as any recording of AF on ECG or an episode longer than 30 s on 24-h Holter recording.</p>
      <p>P-wave indices in each ECG trace was evaluated by two independent blinded investigators and Bland-Altman analyses were performed to assess the inter- and intra-observer reproducibility of P-wave duration, P-wave dispersion, P-wave axis and P-wave terminal force in V1. Measurements showed minimal biases (1.2&#177;11 and 1.3&#177;10 ms, respectively for P wave duration), (1.6&#177;10 and 1.5&#177;10 ms, respectively for P wave dispersion), (2&#177;8 and 2&#177;9 degree, respectively for P wave axis), (1.8+10 and 1.7+10 mm/sec., respectively for P wave terminal force in V1)<sup>8</sup>.</p>
      <p>
        <bold>Radiofrequency Catheter Ablation Procedure</bold>
      </p>
      <p>The ablation procedure was performed in a fasting state. The right femoral vein was used for the insertion of catheters, a single transseptal puncture was performed using FAST-CATH trans-septal guiding introducer (SL1 8.5 F St. Jude medical).Two catheters were inserted: one duodecapolar lasso catheter for PV recording (introduced through the SL0 long sheath and positioned at the ostium of each PV sequentially) and a 4-mm irrigated-tip ablation catheter for pulmonary veins isolation. The right internal jugular vein was used for the insertion of one decapolar (2 mm spacing) steerable catheter in the distal coronary sinus. After transseptal puncture, a bolus of 5000 U of intravenous heparin was administered and activated clotting time was maintained above 280 s throughout the procedure.</p>
      <p>Three-dimensional electro-anatomical mapping was performed in all cases using the CARTO3 system (Biosence Webster, Johnson &amp; Johnson). Radiofrequency catheter ablation was aimed at creating circular lesions initially applied in the whole circumference in the antral region of the veins (ipsilateral vein-to-vein), with subsequent electrical isolation provided it was not achieved in the circumferential application of the lesions. Isolation of all four PVs was performed using the ablation catheter guided by the circumferential mapping catheter in the PV [maximum power 30-35 W; maximal temperature 40; duration of the radiofrequency (RF) application 60 s]. The endpoint of RF application was complete PVI, demonstrated by the absence of PV potentials in the PV during sinus rhythm or coronary sinus pacing, by the absence of PV-left atrium conduction during PV pacing, and by recording of very-low (0.5 mV) voltage inside the PVs in the final voltage map. Reconfirmation of PV isolation was performed 30 min after ablation for each PV. Patients were followed with continuous ECG monitoring for 24 h and were discharged from the hospital two days after the procedure.</p>
      <p>
        <bold>Statistical Analysis</bold>
      </p>
      <p>Data are expressed as mean &#177; standard deviation for continuous variables and frequencies for categorical variables. Differences between groups were assessed using Chi-square statistics for categorical variables and analysis of variance for continuous variables. A p value &lt; 0.05 was considered significant. Pearson's correlation coefficient and multivariate Cox regression analysis using significant variables was also performed. Statistical analyses were performed using SPSS version 16.0 statistical software (SPSS Inc., Chicago, IL). A receiver operating characteristic (ROC) curve was generated to evaluate P wave indices as a predictor of AF recurrences post PVI and different cut-off values for P wave duration and P wave dispersion were chosen to evaluate probability of AF recurrences. The AF-free rates according to P wave duration of &lt; 125 ms and <underline>&gt;</underline> 125 ms along with P wave dispersion &lt; 40 ms and <underline>&gt;</underline> 40 ms were calculated using Kaplan-Meier analysis with the log-rank test.</p>
      <p>
        <bold>Results</bold>
      </p>
      <p>Paroxysmal AF patients in comparison to control cases had longer P wave duration (109.9 &#177; 15.6 ms vs 99.5 &#177; 11.6 ms, p &lt; 0.001), larger P wave dispersion(37.9 &#177; 3.4 ms vs 24.9 &#177; 9.1 ms, p &lt; 0.001), larger left atrial diameter (42.9 &#177; 4.5 mm vs 30 &#177; 6.3 mm, p &lt; 0.001); 66 of 198 patients showed PWTF <underline>&lt;</underline> -0.04 mm/second, while the entire control group had PWTF &gt; -0.04 mm/second (p &lt; 0.0001).</p>
      <p>All patients had successful pulmonary vein isolation and all patients were in sinus rhythm at the end of the procedure. No AF recurrence was observed during the first 24 h after the ablation procedure. During a mean follow-up of 9 &#177; 3 months, recurrences occurred in 30.3% (60/198). The clinical characteristics of the total paroxysmal AF patients and the two groups are summarized in <xref ref-type="table" rid="en_aop_5444tab01-body2">Table 1</xref>.</p>
      <p>Patients with AF recurrence had longer mean P-wave duration (122.9 &#177; 10.3 vs 104.3 &#177; 14.2 ms, p &lt; 0.001), larger P-wave dispersion (40.7 &#177; 1.7 ms vs 36.6 &#177; 3.2 ms, p &lt; 0.001) when compared with patients without recurrence of atrial fibrillation (<xref ref-type="fig" rid="en_aop_5444fig02-body2">Figures 2</xref> and <xref ref-type="fig" rid="en_aop_5444fig03-body2">3</xref>). Further subgroup analysis for patients with normal LA size showed that patients with normal LA size and recurrence of AF post PVI had longer P-wave duration (119.5 &#177; 13.5 ms vs 100.6 &#177;11.38 ms, p = 0.01) and larger P-wave dispersion (38.09 &#177; 2.7 ms vs 35.86 &#177; 3.38 ms, p = 0.03) in comparison with normal LA size patients without recurrence of AF.</p>
      <p content-type="asset">
        <fig id="en_aop_5444fig02-body2">
          <graphic xlink:href="1678-4170-abc-101-06-0519-30214-gf02-en.jpg"/></fig>
      </p>
      <p content-type="asset">
        <fig id="en_aop_5444fig03-body2">
          <graphic xlink:href="1678-4170-abc-101-06-0519-30214-gf03-en.jpg"/></fig>
      </p>
      <p>Forty-eight of 66 (72.7%) patients with P wave terminal force <underline>&lt;</underline> -0.04 mm/second showed recurrence of AF when compared with 12/132 (9%) patients with P-wave terminal force &gt; -0.04 mm/second (p &lt; 0.001). P-wave axis was not significantly different between patients with and without AF recurrences (p &gt; 0.09).</p>
      <p>Receiver operating characteristic (ROC) curve analysis was performed for different P-wave duration and P wave dispersion cutoff points (<xref ref-type="fig" rid="en_aop_5444fig04-body2">Figures 4</xref> and <xref ref-type="fig" rid="en_aop_5444fig05-body2">5</xref>). The area under the ROC curve for P wave duration was 0.858 (95% confidence interval 0.805-0.912) (p &lt; 0.001). The area under the ROC curve for P wave dispersion was 0.852 (95% confidence interval 0.8-0.904) (p &lt; 0.001). By observing different cutoff values, P wave duration <underline>&gt;</underline> 125/ms and P wave dispersion <underline>&gt;</underline> 40 ms were found to discriminate patients prone to AF recurrences over time according to log-rank test (<xref ref-type="fig" rid="en_aop_5444fig06-body2">Figures 6</xref> and <xref ref-type="fig" rid="en_aop_5444fig07-body2">7</xref>). P wave duration of 125 ms has the best combined sensitivity and specificity (60% and 90% respectively) along with positive predictive value of 72% and negative predictive value of 83.7%, whereas P wave dispersion of 40 ms has the best combined sensitivity and specificity (78% and 67% respectively) along with positive predictive value of 51% and negative predictive value of 87.6%.</p>
      <p content-type="asset">
        <fig id="en_aop_5444fig04-body2">
          <graphic xlink:href="1678-4170-abc-101-06-0519-30214-gf04-en.jpg"/></fig>
      </p>
      <p content-type="asset">
        <fig id="en_aop_5444fig05-body2">
          <graphic xlink:href="1678-4170-abc-101-06-0519-30214-gf05-en.jpg"/></fig>
      </p>
      <p content-type="asset">
        <fig id="en_aop_5444fig06-body2">
          <graphic xlink:href="1678-4170-abc-101-06-0519-30214-gf06-en.jpg"/></fig>
      </p>
      <p content-type="asset">
        <fig id="en_aop_5444fig07-body2">
          <graphic xlink:href="1678-4170-abc-101-06-0519-30214-gf07-en.jpg"/></fig>
      </p>
      <p>Multivariate cox regression analysis showed that P wave indices were not independent from left atrial size and age; however, P wave duration was moderately correlated with age (r = 0.3, p &lt; 0.001) and a good correlation with left atrial size (r = 0.5, p &lt; 0.001). No significant correlation was found between P-wave duration and P-wave axis (r = 0.03, p = 0.6). P-wave dispersion had a moderate positive correlation with age (r = 0.41, p &lt; 0.001) and left atrial volume (r = 0.42, p &lt; 0.001). P-wave duration and P-wave dispersion had a moderate positive correlation (r = 0.3, p &lt; 0.001). </p>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>AF is one of the most important arrhythmias found in the field of cardiology, as it is the most prevalent and causes many complications. Several strategies have been used in its management and the importance of AF ablation has increased as it is believed it can cure arrhythmia. The challenge of post ablation atrial fibrillation recurrence is still high, so the present study proposes a non-invasive and easy-to-apply predictor for AF recurrence, which are the P wave indices obtained from standard 12 lead ECG. </p>
      <p>Multiple independent predictors of AF recurrences after RF ablation have been identified, such as age, persistent AF<sup>1</sup>, hypertension, hyperlipidemia, left atrial diameter, white blood cell count before ablation<sup>2,3</sup>, and atrial remodeling by delayed-enhancement MRI<sup>4</sup>, but quantitative non-invasive markers are still lacking.</p>
      <p>Prolonged P-wave duration denotes inter- and intra-atrial abnormal conduction. Dogan et al<sup>9</sup> reported that maximum P wave duration and P wave dispersion were predictors for the maintenance of sinus rhythm after AF cardioversion and that increased P wave dispersion could be used to identify patients at risk of such post procedural recurrence.</p>
      <p>Previous studies were performed to evaluate different P wave duration and dispersion values to predict occurrence of atrial fibrillation post cardioversion, post myocardial infarction and also post-cardiac surgery. Rosiak et al<sup>10</sup> demonstrated that P-wave duration &gt;125 ms and P-wave dispersion &gt;25 ms, when measured very early after an acute myocardial infarction, were independently associated with AF<sup>10</sup>.</p>
      <p>The association between P-wave duration and atrial electromechanical delay assessed by tissue Doppler echocardiography by Dabrowska-Kugacka et al<sup>11</sup> concluded that P-wave duration of the surface ECG is highly correlated with the atrial electromechanical delay and based on this association, one can verify the importance of P-wave duration on the surface ECG as a predictor of atrial fibrillation recurrence post pulmonary vein isolation.</p>
      <p>Other studies that used P-wave signal averaging to predict atrial fibrillation recurrences after pulmonary vein isolation concluded that Filtered P wave duration &gt; 140 ms on the P-wave signal averaged electrocardiogram is a useful marker of AF recurrences over time after pulmonary vein isolation. Although this technique is still not widely used, it confirms that prolonged P-wave duration probably reflects inter- and/or intra-atrial conduction delays and could be related to the extent of atrial scarring and fibrosis, as shown by the longer P-wave duration in patients with recurrent AF<sup>12</sup>.</p>
      <p>P-wave morphology represents atrial electrical activation, which depends mainly on the distance traveled by the electric current from the first to the last point of depolarization, along with the velocity of the electric current. Atrial remodeling, which is the main substrate of AF, is divided mainly into structural and electrical remodeling and in most cases, both will occur together. Structure remodeling is mainly represented by atrial enlargement detected by echocardiography, while electrical remodeling is represented by prolonged electromechanical time demonstrated by tissue Doppler imaging or invasively by measuring total atrial activation time between the first atrial potential detected by an intracardiac electrode positioned in high right atrium and the last atrial potential detected by an intracardiac electrode positioned in distal coronary sinus. The main characteristics of the electrical remodeling process are the shortening of the refractory period with increased dispersion and atrial conductivity reduction. Based on this point of view about atrial electrical remodeling, one can clarify our findings regarding patients with normal LA size, as we found that even in patients with normal LA size patients with recurrence of AF post PVI had longer P wave duration and larger P wave dispersion in comparison with normal LA size patients without AF recurrence.</p>
      <p>AF recurrences post PVI are mainly due to PV re-conduction in ablated myocardium or sometimes to non-PV foci<sup>13-16</sup>. To test the hypothesis that P-wave duration could be a marker of a successful PVI, Date et al<sup>17</sup> studied the contribution of PV cardiac muscles to the P-wave using standard vectorcardiography and electrocardiography recorded before and after the procedure. They found that the morphology of the P-wave changed after PVI and that the myocardial sleeves of the PV played an important role in the formation of the middle part of the P-wave.</p>
      <p>P wave dispersion is still under study and it remains unknown whether it is determined only by heterogeneity of atrial conduction or by other factors as well<sup>18,19</sup>. In our study, we found that P-wave duration <underline>&gt;</underline> 125 ms and P -wave dispersion <underline>&gt;</underline> 40 ms are associated with higher rate of AF recurrence post PVI in patients with paroxysmal AF.</p>
      <p>Large P terminal force in lead V1 along with prolonged P-wave duration predicts left atrial abnormality, particularly in patients with underlying cardiovascular diseases (sensitivity, 82%; specificity, 40%; positive predictive value, 70%; and negative predictive value, 55%) and its presence indicates the need for further evaluation<sup>20</sup>. Moreover, P-wave terminal force in lead V1 has been independently associated with ischemic stroke after adjustment for other stroke risk factors (odds ratio, 2.32; 95% confidence interval, 1.29-4.18)<sup>21</sup>. </p>
      <p>The higher prevalence of PTFV1 <underline>&lt;</underline> -0.04 mm/second in patients with prolonged P-wave duration and wider P-wave dispersion, as noted in our study, probably reflects the associated delayed impulse conduction through already abnormal and enlarged left atria.</p>
      <p>
        <bold>Clinical Implication</bold>
      </p>
      <p>Our findings indicate that P-wave duration, P-wave dispersion along with P wave terminal force in V1 may be useful markers of AF recurrence post PVI, probably reflecting the extent of the atrial disease and remodeling.</p>
      <p>
        <bold>Study Limitation</bold>
      </p>
      <p>Pre-ablation antiarrhythmic drug therapy was not discontinued before radiofrequency catheter ablation; drugs such as amiodarone and flecainide may have influenced the recurrence. AF duration data were derived from the patient's history and ECG recordings; thus, the existence of asymptomatic AF cannot be excluded and the duration of AF might not be accurate. The asymptomatic episodes of AF may also confound the results of AF recurrence during the follow-up. The sample size is relatively small and results of the present study should be confirmed by larger prospective trials.</p>
      <p>
        <bold>Conclusion</bold>
      </p>
      <p>P wave duration <underline>&gt;</underline> 125 ms, P wave dispersion <underline>&gt;</underline> 40 ms, as well as a P wave terminal force in V1 <underline>&lt;</underline> -0.04 mm/sec are good clinical predictors of the already known deleterious sequelae, mainly atrial fibrillation recurrence, post PVI in patients with paroxysmal atrial fibrillation; however, they were not independent from left atrial size and age.</p>
      <p>
        <bold>Author contributions</bold>
      </p>
      <p>Conception and design of the research: Salah A, Zhou S. Acquisition of data: Salah A, Zhou S, Liu Q, Yang H. Analysis and interpretation of the data: Salah A, Zhou S, Liu Q, Yang H. Statistical analysis: Salah A, Zhou S, Yang H. Writing of the manuscript: Salah A, Yang H. Critical revision of the manuscript for intellectual content: Salah A, Zhou S, Liu Q, Yang H. Supervision / as the major investigator: Salah A, Zhou S. Performing pulmonary vein isolation in EP catheter Lab.: Salah A, Liu Q.</p>
      <p>
        <bold>Potential Conflict of Interest</bold>
      </p>
      <p>No potential conflict of interest relevant to this article was reported.</p>
      <p>
        <bold>Sources of Funding</bold>
      </p>
      <p>There were no external funding sources for this study.</p>
      <p>
        <bold>Study Association</bold>
      </p>
      <p>This study is not associated with any post-graduation program.</p>
      <p>
        <bold>References</bold>
      </p>
    </body>
  </sub-article>
</article>
