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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">yjkY4KSVhLgddc9tP3xtYgt</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2013003100010</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(13)10100500010</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20130190</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>A dissincronia mec&#226;nica &#233; semelhante em diferentes padr&#245;es do bloqueio de ramo esquerdo</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Barretto</surname>
            <given-names>Rodrigo Bellio de Mattos</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Piegas</surname>
            <given-names>Leopoldo Soares</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Assef</surname>
            <given-names>Jorge Eduardo</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Melo Neto</surname>
            <given-names>Jos&#233; Francisco</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Resende</surname>
            <given-names>Thiago Uchoa</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Moreira</surname>
            <given-names>Dalmo Antonio</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>LeBihan</surname>
            <given-names>David Costa</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Fran&#231;a</surname>
            <given-names>Francisco Faustino</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Meneghelo</surname>
            <given-names>Romeu S&#233;rgio</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Sousa</surname>
            <given-names>Amanda Guerra Moraes Rego</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">S&#227;o Paulo</named-content>
        </addr-line>
        <institution content-type="orgname">Instituto Dante Pazzanese de Cardiologia</institution>
        <country country="BR">Brazil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>11</month>
        <year>2013</year>
      </pub-date>
      <volume>101</volume>
      <issue>5</issue>
      <fpage>449</fpage>
      <lpage>456</lpage>
      <history>
        <date date-type="received">
          <day>06</day>
          <month>11</month>
          <year>2012</year>
        </date>
        <date date-type="accepted">
          <day>26</day>
          <month>06</month>
          <year>2013</year>
        </date>
        <date date-type="rev-recd">
          <day>19</day>
          <month>06</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>FUNDAMENTOS: O bloqueio do ramo esquerdo (BRE) e a presen&#231;a de disfun&#231;&#227;o sist&#243;lica s&#227;o as principais indica&#231;&#245;es de terapia de ressincroniza&#231;&#227;o card&#237;aca (TRC). A dissincronia ventricular mec&#226;nica pela ecocardiografia pode ajudar a identificar pacientes responsivos &#224; TRC. O BRE pode mostrar diferentes padr&#245;es em sua morfologia. OBJETIVO: Comparar a preval&#234;ncia de dissincronia mec&#226;nica em diferentes padr&#245;es de BRE em pacientes com disfun&#231;&#227;o sist&#243;lica esquerda. M&#201;TODOS: Analisaram-se 48 pacientes com fra&#231;&#227;o de eje&#231;&#227;o (FE) &lt; 40% e BRE referidos consecutivamente para an&#225;lise de dissincronia. Foram realizados ecocardiograma convencional e an&#225;lise da dissincronia mec&#226;nica, interventricular e intraventricular, por 10 conhecidos m&#233;todos, usando modo M, Doppler e Doppler tecidual, sozinhos ou combinados. A morfologia do BRE foi categorizada pelo desvio esquerdo do eixo no plano frontal e dura&#231;&#227;o de QRS &gt; 150 ms. RESULTADOS: Eram 24 homens, com idade 60 &#177; 11 anos e FEVE de 29 &#177; 7%. Trinta e dois apresentavam QRS &gt; 150 ms, e 22, ECG eixo entre -30&#186; e +90&#186;. A dissincronia interventricular foi identificada em 73% dos pacientes e a intraventricular em valores entre 37-98%. Portadores de QRS &gt; 150 ms apresentaram maiores dimens&#245;es do &#225;trio e ventr&#237;culo esquerdos, e menor FE (p &lt; 0,05), e o desvio esquerdo do eixo associou-se a pior fun&#231;&#227;o diast&#243;lica e maior di&#226;metro atrial. A presen&#231;a de dissincronia mec&#226;nica interventricular e intraventricular (10 m&#233;todos) foi semelhante entre os diferentes padr&#245;es de BRE (p = ns). CONCLUS&#195;O: Nos dois diferentes padr&#245;es eletrocardiogr&#225;ficos de BRE analisados, n&#227;o foram observadas diferen&#231;as em rela&#231;&#227;o &#224; presen&#231;a de dissincronia mec&#226;nica.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Bloqueio de Ramo</kwd>
        <kwd>Disfun&#231;&#227;o Ventricular</kwd>
        <kwd>Terapia de Ressincroniza&#231;&#227;o Card&#237;aca</kwd>
        <kwd>Volume Sist&#243;lico</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>24</day>
        <month>09</month>
        <year>2013</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>A dissincronia mec&#226;nica &#233; semelhante em diferentes padr&#245;es do bloqueio de ramo esquerdo</bold>
    </p>
    <p>
      <bold>Rodrigo Bellio de Mattos Barretto; Leopoldo Soares Piegas; Jorge Eduardo Assef; Jos&#233; Francisco Melo Neto; Thiago Uchoa Resende; Dalmo Antonio Moreira; David Costa LeBihan; Francisco Faustino Fran&#231;a; Romeu S&#233;rgio Meneghelo; Amanda Guerra Moraes Rego Sousa</bold>
    </p>
    <p>Instituto Dante Pazzanese de Cardiologia, S&#227;o Paulo, SP - Brasil</p>
    <p>
      <xref ref-type="corresp" rid="enda">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>FUNDAMENTOS:</bold> O bloqueio do ramo esquerdo (BRE) e a presen&#231;a de disfun&#231;&#227;o sist&#243;lica s&#227;o as principais indica&#231;&#245;es de terapia de ressincroniza&#231;&#227;o card&#237;aca (TRC). A dissincronia ventricular mec&#226;nica pela ecocardiografia pode ajudar a identificar pacientes responsivos &#224; TRC. O BRE pode mostrar diferentes padr&#245;es em sua morfologia. </p>
    <p><bold>OBJETIVO:</bold> Comparar a preval&#234;ncia de dissincronia mec&#226;nica em diferentes padr&#245;es de BRE em pacientes com disfun&#231;&#227;o sist&#243;lica esquerda. </p>
    <p><bold> M&#201;TODOS:</bold> Analisaram-se 48 pacientes com fra&#231;&#227;o de eje&#231;&#227;o (FE) &lt; 40% e BRE referidos consecutivamente para an&#225;lise de dissincronia. Foram realizados ecocardiograma convencional e an&#225;lise da dissincronia mec&#226;nica, interventricular e intraventricular, por 10 conhecidos m&#233;todos, usando modo M, Doppler e Doppler tecidual, sozinhos ou combinados. A morfologia do BRE foi categorizada pelo desvio esquerdo do eixo no plano frontal e dura&#231;&#227;o de QRS &gt; 150 ms. </p>
    <p><bold>RESULTADOS:</bold> Eram 24 homens, com idade 60 &#177; 11 anos e FEVE de 29 &#177; 7%. Trinta e dois apresentavam QRS &gt; 150 ms, e 22, ECG eixo entre -30&#186; e +90&#186;. A dissincronia interventricular foi identificada em 73% dos pacientes e a intraventricular em valores entre 37-98%. Portadores de QRS &gt; 150 ms apresentaram maiores dimens&#245;es do &#225;trio e ventr&#237;culo esquerdos, e menor FE (p &lt; 0,05), e o desvio esquerdo do eixo associou-se a pior fun&#231;&#227;o diast&#243;lica e maior di&#226;metro atrial. A presen&#231;a de dissincronia mec&#226;nica interventricular e intraventricular (10 m&#233;todos) foi semelhante entre os diferentes padr&#245;es de BRE (p = ns). </p>
    <p><bold> CONCLUS&#195;O:</bold> Nos dois diferentes padr&#245;es eletrocardiogr&#225;ficos de BRE analisados, n&#227;o foram observadas diferen&#231;as em rela&#231;&#227;o &#224; presen&#231;a de dissincronia mec&#226;nica. </p>
    <p><bold>Palavras-chave:</bold> Bloqueio de Ramo; Disfun&#231;&#227;o Ventricular; Terapia de Ressincroniza&#231;&#227;o Card&#237;aca; Volume Sist&#243;lico.</p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p>A insufici&#234;ncia card&#237;aca, uma s&#237;ndrome cl&#237;nica resultante da disfun&#231;&#227;o card&#237;aca estrutural e/ou funcional, &#233; reconhecidamente o est&#225;gio final de v&#225;rias cardiopatias. As altera&#231;&#245;es eletrocardiogr&#225;ficas, como o bloqueio de ramo esquerdo (BRE), s&#227;o achados comuns em pacientes portadores de insufici&#234;ncia card&#237;aca, principalmente quando ocorre disfun&#231;&#227;o sist&#243;lica<sup>1,2</sup>.</p>
    <p>H&#225;, na atualidade, v&#225;rias op&#231;&#245;es de tratamento da insufici&#234;ncia card&#237;aca. Uma das alternativas terap&#234;uticas com comprovada efici&#234;ncia &#233; a terapia de ressincroniza&#231;&#227;o card&#237;aca<sup>3</sup> (TCR). A indica&#231;&#227;o do implante de marca-passo ressincronizador &#233; baseada em preenchimento de crit&#233;rios cl&#237;nicos e eletrocardiogr&#225;ficos, e tamb&#233;m em informa&#231;&#245;es obtidas pelo ecocardiograma. No eletrocardiograma, o aumento da largura do complexo QRS, como observado no BRE, &#233; a condi&#231;&#227;o mais frequente para indica&#231;&#227;o desse tratamento<sup>4-6</sup>. No entanto, o insucesso do tratamento ocorre em aproximadamente 30% dos casos em diversas s&#233;ries descritas na literatura<sup>3</sup>.</p>
    <p>Al&#233;m das informa&#231;&#245;es j&#225; classicamente conhecidas, como a dimens&#227;o do ventr&#237;culo esquerdo e de sua fra&#231;&#227;o de eje&#231;&#227;o, o ecocardiograma permite a an&#225;lise do sincronismo interventricular e intraventricular, que &#233; o foco da TRC. Diferentes m&#233;todos, utilizando diversas t&#233;cnicas ecocardiogr&#225;ficas, t&#234;m sido empregados na detec&#231;&#227;o e na estratifica&#231;&#227;o da dissincronia<sup>7,8</sup>, possibilitando predizer aqueles que apresentam bons resultados com esse tipo de tratamento.</p>
    <p>O bloqueio de ramo esquerdo pode apresentar diferentes caracter&#237;sticas relacionadas a maior morbidade e mortalidade<sup>9,10</sup>. A rela&#231;&#227;o entre diferentes caracter&#237;sticas do bloqueio de ramo esquerdo e a dissincronia avaliada pelo ecocardiograma ainda n&#227;o foi estabelecida, o que pode ter uma participa&#231;&#227;o na taxa de insucesso dessa terapia.</p>
    <p>
      <bold>Objetivos</bold>
    </p>
    <p>O objetivo deste estudo foi o de comparar os achados ecocardiogr&#225;ficos convencionais e da sincronia ventricular relacionados a diferentes morfologias do BRE em pacientes com disfun&#231;&#227;o ventricular sist&#243;lica esquerda.</p>
    <p>
      <bold>M&#233;todos</bold>
    </p>
    <p>O estudo foi aprovado pelo Comit&#234; de &#201;tica em Pesquisa do Instituto Dante Pazzanese de Cardiologia.</p>
    <p>
      <bold>Popula&#231;&#227;o do estudo</bold>
    </p>
    <p>Foram avaliados pacientes ambulatoriais, em tratamento de insufici&#234;ncia card&#237;aca encaminhados para a se&#231;&#227;o de ecocardiografia com disfun&#231;&#227;o sist&#243;lica caracterizada por fra&#231;&#227;o de eje&#231;&#227;o, pelo m&#233;todo de Simpson, abaixo de 40%. Todos os pacientes apresentavam ritmo sinusal e BRE<sup>11</sup>. Foram exclu&#237;dos pacientes menores de idade, portadores de marca-passo, assim como aqueles submetidos a cirurgia valvar pr&#233;via ou com valvopatia a&#243;rtica de qualquer grau. Os dados cl&#237;nicos quanto &#224; classe funcional, antecedentes e medica&#231;&#245;es em uso foram tamb&#233;m avaliados.</p>
    <p>
      <bold>ECG</bold>
    </p>
    <p>O eletrocardiograma foi realizado em 12 deriva&#231;&#245;es. Foram medidos os intervalos PR e a largura do complexo QRS, assim como caracter&#237;sticas do eixo frontal. Os pacientes foram analisados em grupos de acordo com a presen&#231;a de intervalo QRS &gt; 150 ms e pela presen&#231;a de desvio do eixo el&#233;trico &#224; esquerda no plano frontal, isto &#233;, valores do eixo frontal menores que -30&#186;.</p>
    <p>
      <bold>Ecocardiograma</bold>
    </p>
    <p>O ecocardiograma foi realizado em aparelho Vivid7<sup>&#174;</sup> (GE Vingmed, System VII, Horton, Noruega). As imagens foram adquiridas na forma de clipes digitais. Posteriormente, as medidas, lineares e bidimensionais, foram realizadas conforme as diretrizes da Sociedade Americana de Ecocardiografia, utilizando-se uma m&#233;dia de tr&#234;s ciclos consecutivos em esta&#231;&#227;o de trabalho EchoPAC PC version 6.0.1<sup>&#174;</sup> (GE Vingmed Ultrasound). Tamb&#233;m houve caracteriza&#231;&#227;o da fun&#231;&#227;o diast&#243;lica por meio das diretrizes da Sociedade Americana de Ecocardiografia, assim como a quantifica&#231;&#227;o da regurgita&#231;&#227;o valvar mitral<sup>12,13</sup>.</p>
    <p>A dissincronia interventricular foi avaliada como a diferen&#231;a entre os intervalos pr&#233;-ejetivos, isto &#233;, do in&#237;cio do QRS at&#233; os in&#237;cios da eje&#231;&#227;o ventricular nas valvas a&#243;rtica e pulmonar, utilizando-se o Doppler puls&#225;til, sendo considerada presente quando esse valor excedia 40 ms<sup>14,15</sup>. A dissincronia intraventricular mec&#226;nica foi avaliada por meio de diversas metodologias relatadas na literatura, cujos valores de corte foram descritos como marcadores de sucesso da TRC. A an&#225;lise foi efetuada por meio de crit&#233;rios como: 1) intervalo de tempo decorrido entre o deslocamento sist&#243;lico do septo e a parede posterior, em modo M &gt; 130 ms, como descrito por Pitzalis e cols.<sup>16</sup>; 2) maior intervalo entre o deslocamento sist&#243;lico m&#225;ximo de seis segmentos basais do ventr&#237;culo esquerdo superior a 110 ms aferidos por meio do Doppler tecidual, como demonstrado por Notabartolo e cols.<sup>17</sup>; 3) valor do intervalo entre o deslocamento sist&#243;lico m&#225;ximo entre o septo e a parede lateral ao Doppler tecidual &gt; 65 ms, como descrito por Gorcsan e cols.<sup>18</sup>; 4) presen&#231;a de crit&#233;rio positivo no escore do Hospital Saint Mary, Reino Unido, descrito por Lane e cols.<sup>19</sup>; 5) crit&#233;rio positivo para a presen&#231;a de dissincronia, como estabelecido por Cleland e cols.<sup>14</sup>, no estudo CARE-HF; 6) valor do desvio-padr&#227;o entre os tempos de deslocamento m&#225;ximo, medidos pelo Doppler tecidual, em 12 segmentos do ventr&#237;culo esquerdo superior a 32 ms, proposto por Yu e cols.<sup>7</sup>; 7) valores superiores a 60 ms entre o intervalo de in&#237;cio de deslocamento sist&#243;lico do anel mitral em quatro segmentos medidos pelo Doppler tecidual, como mostrado por De Sutter e cols.<sup>20</sup>; 8) valores superiores a 100 ms entre o intervalo de final de deslocamento sist&#243;lico do anel mitral em quatro segmentos medidos pelo Doppler tecidual, como descrito por Perez de Isla e cols.<sup>21</sup>, no registro de assincronia ventricular espanhol - RAVE; 9) intervalo entre a contra&#231;&#227;o m&#225;xima do segmento anterosseptal e posterior &gt; 130 ms medido pelo strain bidimensional associado a intervalo entre o deslocamento sist&#243;lico m&#225;ximo entre o septo e a parede lateral ao Doppler tecidual &gt; 60 ms, como demonstrado por Gorcsan e cols.<sup>22</sup>.</p>
    <p>
      <bold>An&#225;lise estat&#237;stica</bold>
    </p>
    <p>As vari&#225;veis quantitativas est&#227;o descritas em m&#233;dia &#177; desvio-padr&#227;o, e as qualitativas, em porcentagem. Aplicou-se o teste t de Student, Wilcoxon, o teste do qui-quadrado e o teste de Fisher, quando apropriados, para compara&#231;&#245;es entre as diferentes apresenta&#231;&#245;es do bloqueio de ramo esquerdo. O software JMP8,0<sup>&#174;</sup> (Institute Inc., Carry, Carolina do Norte) foi usado para realiza&#231;&#227;o dos c&#225;lculos. Foi considerado n&#237;vel de signific&#226;ncia de 5%.</p>
    <p>
      <bold>Resultados</bold>
    </p>
    <p>As caracter&#237;sticas cl&#237;nicas dos 48 pacientes estudados s&#227;o apresentadas na <xref ref-type="table" rid="tab01">Tabela 1</xref>, e as do eletrocardiograma encontram-se na <xref ref-type="table" rid="tab02">Tabela 2</xref>, onde se observa a utiliza&#231;&#227;o em aproximadamente 90% dos indiv&#237;duos de betabloqueadores e inibidores de enzima de convers&#227;o/bloqueadores dos receptores de angiotensina. As vari&#225;veis aferidas pelo ecocardiograma s&#227;o demonstradas na <xref ref-type="table" rid="aop_5253tab03">Tabela 3</xref>, com graus vari&#225;veis da presen&#231;a de dissincronia intraventricular de acordo com os crit&#233;rios utilizados.</p>
    <p content-type="asset">
      <table-wrap id="aop_5253tab03">
        <graphic xlink:href="1678-4170-abc-101-05-0449-30190-gt01.jpg"/></table-wrap>
    </p>
    <table-wrap id="tab01">
      <graphic xlink:href="1678-4170-abc-101-05-0449-30190-gt02.jpg"/></table-wrap>
    <table-wrap id="tab02">
      <graphic xlink:href="1678-4170-abc-101-05-0449-30190-gt03.jpg"/></table-wrap>
    <p>Quando os pacientes foram comparados quanto &#224;s diferentes morfologias de BRE, observou-se que a dura&#231;&#227;o do QRS superior a 150 ms e o eixo no plano frontal &lt; -30&#186; eixo n&#227;o estiveram relacionadas a diferen&#231;as em rela&#231;&#227;o a g&#234;nero, idade, antecedentes, classe funcional ou medica&#231;&#245;es em uso, como demonstrado nas <xref ref-type="table" rid="aop_5253tab04">Tabelas 4</xref> e <xref ref-type="table" rid="aop_5253tab05">5</xref>.</p>
    <p content-type="asset">
      <table-wrap id="aop_5253tab04">
        <graphic xlink:href="1678-4170-abc-101-05-0449-30190-gt04.jpg"/></table-wrap>
    </p>
    <p content-type="asset">
      <table-wrap id="aop_5253tab05">
        <graphic xlink:href="1678-4170-abc-101-05-0449-30190-gt05.jpg"/></table-wrap>
    </p>
    <p>Em rela&#231;&#227;o ao ecocardiograma, pacientes com intervalo QRS superior a 150 ms apresentaram dimens&#245;es lineares e volumes do ventr&#237;culo esquerdo maiores, maiores di&#226;metros do &#225;trio esquerdo e menor FE, mostrado na <xref ref-type="table" rid="aop_5253tab04">Tabela 4</xref>.</p>
    <p>Na an&#225;lise dos pacientes que apresentavam a orienta&#231;&#227;o do eixo el&#233;trico no plano frontal desviada para a esquerda, -30&#186;, observaram-se maiores di&#226;metros do &#225;trio esquerdo e associa&#231;&#227;o com piores graus de disfun&#231;&#227;o diast&#243;lica do ventr&#237;culo esquerdo, assim como maior di&#226;metro do ventr&#237;culo esquerdo, como evidenciado na <xref ref-type="table" rid="aop_5253tab05">Tabela 5</xref>.</p>
    <p>A an&#225;lise da dissincronia interventricular e intraventricular foi semelhante em rela&#231;&#227;o ao grupo com maior dura&#231;&#227;o do intervalo QRS e com desvio do eixo el&#233;trico no plano frontal para a esquerda (ver as <xref ref-type="table" rid="aop_5253tab04">Tabelas 4</xref> e <xref ref-type="table" rid="aop_5253tab05">5</xref>).</p>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>A presen&#231;a de diferentes apresenta&#231;&#245;es do BRE n&#227;o possibilita identificar um padr&#227;o de dissincronia, tampouco se caracteriza por apresentar diferentes preval&#234;ncias em rela&#231;&#227;o &#224;s diversas metodologias avaliadas por meio da ecocardiografia.</p>
    <p>No entanto, os padr&#245;es do BRE apresentam rela&#231;&#227;o com altera&#231;&#245;es morfol&#243;gicas e funcionais do ventr&#237;culo esquerdo, onde intervalos mais longos do QRS associam-se a maiores dimens&#245;es do ventr&#237;culo esquerdo, e o desvio do eixo para a esquerda no eletrocardiograma tem rela&#231;&#227;o com o grau mais avan&#231;ado de disfun&#231;&#227;o diast&#243;lica e maior dimens&#227;o do &#225;trio esquerdo.</p>
    <p>Esses achados corroboram o estudo pr&#233;vio de Das e cols.<sup>23</sup>, no qual se demonstrou que a fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo &#233; mais comprometida quando h&#225; aumento da dura&#231;&#227;o do QRS em pacientes com BRE, por&#233;m n&#227;o se associa ao desvio do eixo para a esquerda. Por outro lado, a maior incid&#234;ncia de eventos, descrita por Dhingra e cols.<sup>24</sup> em pacientes com BRE e desvio do eixo para a esquerda deve estar associada a maiores graus de disfun&#231;&#227;o diast&#243;lica, que &#233; comprovado fator relacionado &#224; mortalidade<sup>25</sup>.</p>
    <p>Apesar de nem todos os pacientes preencherem os crit&#233;rios propostos pelas &#250;ltimas diretrizes para implante de marca-passo ressincronizador<sup>5</sup>, essas indica&#231;&#245;es t&#234;m se modificado, e a maioria dos pacientes estudados constitui um grupo que &#233; candidato &#224; TRC, inclusive pacientes com FE &lt; 40%<sup>5,26</sup>. Os dados permitem supor a falta de rela&#231;&#227;o de intervalos mais longos do QRS no BRE e a resposta a esse tipo de tratamento<sup>27</sup>, pois a preval&#234;ncia da dissincronia mec&#226;nica &#233; semelhante, independentemente do m&#233;todo utilizado pelo ecocardiograma.</p>
    <p>Apesar das limita&#231;&#245;es do emprego do ecocardiograma como m&#233;todo para a sele&#231;&#227;o de pacientes candidatos a implante de marca-passo com capacidade de ressincroniza&#231;&#227;o evidenciado no estudo PROSPECT<sup>28</sup>, os m&#233;todos utilizados apresentaram em sua maioria a capacidade de distinguir pacientes que se beneficiaram dessa terapia, sendo descritos diversos m&#233;todos ecocardiogr&#225;ficos que, em estudos unic&#234;ntricos, possibilitaram evidenciar a melhor resposta a ela.</p>
    <p>Sweeney e cols.<sup>29</sup> mostraram em um estudo que a descri&#231;&#227;o convencional do eletrocardiograma em pacientes com BRE, como a dura&#231;&#227;o do intervalo QRS e a presen&#231;a de desvio de seu eixo para a esquerda, s&#227;o insuficientes para prever os indiv&#237;duos que apresentam melhora ecocardiogr&#225;fica ap&#243;s a ressincroniza&#231;&#227;o card&#237;aca por meio do marca-passo. No entanto, evid&#234;ncia ao eletrocardiograma de maior tempo de ativa&#231;&#227;o do ventr&#237;culo esquerdo e menor volume de cicatriz caracterizam o grupo de pacientes com melhor resposta ao ressincronizador. Tais medidas n&#227;o foram analisadas no presente estudo, assim como o estudo de Sweeney e cols.<sup>29</sup> n&#227;o comparou esses achados eletrocardiogr&#225;ficos com a avalia&#231;&#227;o da sincronia mec&#226;nica por meio da ecocardiografia, podendo essa rela&#231;&#227;o ser testada futuramente.</p>
    <p>
      <bold>Conclus&#227;o</bold>
    </p>
    <p>Diferentes apresenta&#231;&#245;es de BRE n&#227;o possibilitam diferenciar pacientes com maior chance de dissincronia mec&#226;nica evidenciada por diversos m&#233;todos ecocardiogr&#225;ficos, por&#233;m &#233; poss&#237;vel associ&#225;-los a padr&#245;es reconhecidamente de risco, como a redu&#231;&#227;o da fra&#231;&#227;o de eje&#231;&#227;o e maiores graus de disfun&#231;&#227;o diast&#243;lica.</p>
    <p>
      <bold>Contribui&#231;&#227;o dos autores</bold>
    </p>
    <p>Concep&#231;&#227;o e desenho da pesquisa: Barretto RBM, Piegas LS, Moreira DA, Fran&#231;a FF; Obten&#231;&#227;o de dados: Barretto RBM, Melo Neto JF, Resende TU; An&#225;lise e interpreta&#231;&#227;o dos dados: Barretto RBM, Piegas LS, Assef JE, Melo Neto JF, Resende TU, Moreira DA, Fran&#231;a FF; An&#225;lise estat&#237;stica e Obten&#231;&#227;o de financiamento: Barretto RBM; Reda&#231;&#227;o do manuscrito: Barretto RBM, Piegas LS, Assef JE; Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual: Barretto RBM, Assef JE, LeBihan DC, Meneghelo RS, Sousa AGMR.</p>
    <p>
      <bold>Potencial Conflito de Interesses</bold>
    </p>
    <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
    <p>
      <bold>Fontes de Financiamento</bold>
    </p>
    <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
    <p>
      <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
    </p>
    <p>Este artigo &#233; parte de tese de Doutorado de Rodrigo Bellio de Mattos Barretto pela Universidade de S&#227;o Paulo.</p>
    <p>
      <fn id="enda" fn-type="corresp">
        <label>
          <bold>Correspond&#234;ncia:</bold>
        </label>
        <p> Rodrigo Bellio de Mattos Barretto </p>
        <p> Rua Alagoas, 134, apt 91, Higien&#243;polis </p>
        <p> CEP 01242-000, S&#227;o Paulo, SP - Brasil </p>
        <p> E-mail: </p>
        <p><email xlink:href="barretto.rodrigo@terra.com.br">barretto.rodrigo@terra.com.br</email>, </p>
        <p>
          <email xlink:href="barrettorbm@hotmail.com">barrettorbm@hotmail.com</email>
        </p>
      </fn>
    </p>
    <p>Artigo recebido em 06/11/12; revisado em 19/06/13; aceito em 26/06/13.</p>
  </body>
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        <mixed-citation>30. Yu CM, Zhang Q, Fung JW, Chan HC, Chan YS, Yip GW, et al. A novel tool to assess systolic asynchrony and identify responders of cardiac resynchronization therapy by tissue synchronization imaging. J Am Coll Cardiol. 2005;45(5):677-84.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>A novel tool to assess systolic asynchrony and identify responders of cardiac resynchronization therapy by tissue synchronization imaging</article-title>
          <source>J Am Coll Cardiol</source>
          <date>
            <year>2005</year>
          </date>
          <fpage>677</fpage>
          <lpage>84</lpage>
          <issue>5</issue>
          <volume>45</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Yu</surname>
              <given-names>CM</given-names>
            </name>
            <name>
              <surname>Zhang</surname>
              <given-names>Q</given-names>
            </name>
            <name>
              <surname>Fung</surname>
              <given-names>JW</given-names>
            </name>
            <name>
              <surname>Chan</surname>
              <given-names>HC</given-names>
            </name>
            <name>
              <surname>Chan</surname>
              <given-names>YS</given-names>
            </name>
            <name>
              <surname>Yip</surname>
              <given-names>GW</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">Mechanical dyssynchrony is similar in different patterns of left bundle-branch block</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>BACKGROUND: Left bundle-branch block (LBBB) and the presence of systolic dysfunction are the major indications for cardiac resynchronization therapy (CRT). Mechanical ventricular dyssynchrony on echocardiography can help identify patients responsive to CRT. Left bundle-branch block can have different morphologic patterns. OBJECTIVE: To compare the prevalence of mechanical dyssynchrony in different patterns of LBBB in patients with left systolic dysfunction. METHODS: This study assessed 48 patients with ejection fraction (EF) &lt; 40% and LBBB consecutively referred for dyssynchrony analysis. Conventional echocardiography and mechanical dyssynchrony analysis were performed, interventricular and intraventricular, with ten known methods, using M mode, Doppler and tissue Doppler imaging, isolated or combined. The LBBB morphology was categorized according to left electrical axis deviation in the frontal plane and QRS duration &gt; 150 ms. RESULTS: The patients' mean age was 60 &#177; 11 years, 24 were males, and mean EF was 29% &#177; 7%. Thirty-two had QRS &gt; 150 ms, and22, an electrical axis between -30&#186; and +90&#186;. Interventricular dyssynchrony was identified in 73% of the patients, while intraventricular dyssynchrony, in 37%-98%. Patients with QRS &gt; 150 ms had larger left atrium and ventricle, and lower EF (p &lt; 0.05). Left electrical axis deviation associated with worse diastolic function and greater atrial diameter. Interventricular and intraventricular mechanical dyssynchrony (ten methods) was similar in the different LBBB patterns (p = ns). CONCLUSION: In the two different electrocardiographic patterns of LBBB analyzed, no difference regarding the presence of mechanical dyssynchrony was observed.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Bundle-Branch Block</kwd>
        <kwd>Ventricular Dysfunction</kwd>
        <kwd>Cardiac Resynchronization Therapy</kwd>
        <kwd>Stroke Volume</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <fn id="end-body2">
          <label>
            <bold>Mechanical dyssynchrony is similar in different patterns of left bundle-branch block</bold>
          </label>
          <p>
            <bold>Rodrigo Bellio de Mattos Barretto; Leopoldo Soares Piegas; Jorge Eduardo Assef; Jos&#233; Francisco Melo Neto; Thiago Uchoa Resende; Dalmo Antonio Moreira; David Costa LeBihan; Francisco Faustino Fran&#231;a; Romeu S&#233;rgio Meneghelo; Amanda Guerra Moraes Rego Sousa</bold>
          </p>
        </fn>
      </p>
      <p>Instituto Dante Pazzanese de Cardiologia, S&#227;o Paulo, SP - Brazil</p>
      <p>Mailing Address</p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p><bold>BACKGROUND:</bold> Left bundle-branch block (LBBB) and the presence of systolic dysfunction are the major indications for cardiac resynchronization therapy (CRT). Mechanical ventricular dyssynchrony on echocardiography can help identify patients responsive to CRT. Left bundle-branch block can have different morphologic patterns.</p>
      <p><bold>OBJECTIVE:</bold> To compare the prevalence of mechanical dyssynchrony in different patterns of LBBB in patients with left systolic dysfunction.</p>
      <p><bold>METHODS:</bold> This study assessed 48 patients with ejection fraction (EF) &lt; 40% and LBBB consecutively referred for dyssynchrony analysis. Conventional echocardiography and mechanical dyssynchrony analysis were performed, interventricular and intraventricular, with ten known methods, using M mode, Doppler and tissue Doppler imaging, isolated or combined. The LBBB morphology was categorized according to left electrical axis deviation in the frontal plane and QRS duration &gt; 150 ms.</p>
      <p><bold>RESULTS:</bold> The patients' mean age was 60 &#177; 11 years, 24 were males, and mean EF was 29% &#177; 7%. Thirty-two had QRS &gt; 150 ms, and 22, an electrical axis between -30&#186; and +90&#186;. Interventricular dyssynchrony was identified in 73% of the patients, while intraventricular dyssynchrony, in 37%-98%. Patients with QRS &gt; 150 ms had larger left atrium and ventricle, and lower EF (p &lt; 0.05). Left electrical axis deviation associated with worse diastolic function and greater atrial diameter. Interventricular and intraventricular mechanical dyssynchrony (ten methods) was similar in the different LBBB patterns (p = ns).</p>
      <p><bold>CONCLUSION:</bold> In the two different electrocardiographic patterns of LBBB analyzed, no difference regarding the presence of mechanical dyssynchrony was observed.</p>
      <p><bold>Keywords:</bold> Bundle-Branch Block; Ventricular Dysfunction; Cardiac Resynchronization Therapy; Stroke Volume.</p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p>Heart failure, a clinical syndrome resulting from structural and/or functional cardiac dysfunction, is known to be the end stage of several cardiopathies. Electrocardiographic alterations, such as left bundle-branch block (LBBB), are common findings in patients with heart failure, mainly in the presence of systolic dysfunction<sup>1,2</sup>.</p>
      <p>Currently, there are several treatment options for heart failure. One efficient alternative is cardiac resynchronization therapy<sup>3</sup> (CRT). The indication for implantation of a resynchronizing pacemaker is based on clinical and electrocardiographic criteria, and echocardiographic data. On the electrocardiogram, QRS complex enlargement, as observed in LBBB, is the most frequent indication for that treatment<sup>4-6</sup>. However, treatment failure has been reported in approximately 30% of the cases in several series<sup>3</sup>.</p>
      <p>In addition to the already known classic information, such as left ventricular dimension and ejection fraction, echocardiography allows the analysis of interventricular and intraventricular synchronism, which is the focus of CRT. Different methods, using several echocardiographic techniques, have been used to detect and stratify dyssynchrony<sup>7,8</sup>, enabling predicting those who will have good results with a certain treatment.</p>
      <p>Left bundle-branch block can have different characteristics related to higher morbidity and mortality<sup>9,10</sup>. The relationship between different characteristics of LBBB and dyssynchrony assessed on echocardiography is yet to be established, which might contribute to the lack of success of that therapy.</p>
      <p>
        <bold>Objectives</bold>
      </p>
      <p>This study aimed at comparing conventional echocardiographic findings and those of ventricular synchrony related to different LBBB morphologies in patients with left ventricular systolic dysfunction.</p>
      <p>
        <bold>Methods</bold>
      </p>
      <p>This study was approved by the Committee on Ethics and Research of the Instituto Dante Pazzanese de Cardiologia.</p>
      <p>
        <bold>Study population</bold>
      </p>
      <p>This study assessed individuals followed up on an outpatient basis for heart failure treatment, who were referred to the echocardiography section with systolic dysfunction characterized by ejection fraction below 40%, according to the Simpson's method. All patients had sinus rhythm and LBBB<sup>11</sup>. Patients with the following characteristics were excluded: under the age of 18 years; wearing a pacemaker; and those who had undergone previous valvular surgery or had any degree of aortic valvulopathy. The clinical data concerning functional class, history and medications used were also assessed.</p>
      <p>
        <bold>Electrocardiogram</bold>
      </p>
      <p>Twelve-lead electrocardiography was performed. The PR intervals and QRS complexes were measured, and the frontal axis characteristics were assessed. The patients were classified into two groups according to the presence of QRS interval &gt; 150 ms or left electrical axis deviation in the frontal plane, i.e. , frontal axis values &lt; -30&#186;.</p>
      <p>
        <bold>Echocardiogram</bold>
      </p>
      <p>Echocardiogram was performed on a Vivid7<sup>&#174;</sup> device (GE Vingmed, System VII, Horton, Norway). The images were acquired as digital clips. Then, linear and two-dimensional measures were taken according to the American Society of Echocardiography guidelines, using a mean of three consecutive cycles on a EchoPAC PC work station, version 6.0.1<sup>&#174;</sup> (GE Vingmed Ultrasound). Diastolic function was also characterized according to the American Society of Echocardiography guidelines, and mitral valve regurgitation was quantified<sup>12,13</sup>.</p>
      <p>Interventricular dyssynchrony was assessed as the difference between pre-ejection intervals, i.e. , from the beginning of the QRS complex to the beginning of the ventricular ejection into the aortic and pulmonary valves, using pulsed Doppler; interventricular dyssynchrony was considered to exist when that value exceeded 40 ms<sup>14,15</sup>. According to the literature, mechanical intraventricular dyssynchrony has been assessed by use of several methodologies, whose cutoff points have been described as markers of successful CRT. The analysis was performed according to the following criteria: 1) septal-to-posterior wall motion delay, in M mode, &gt; 130 ms, as reported by Pitzalis et al<sup>16</sup>; 2) greater interval between maximum systolic motion of six left ventricular basal segments &gt; 110 ms, measured on tissue Doppler, as demonstrated by Notabartolo et al<sup>17</sup>; 3) maximum systolic motion interval between the septum and lateral wall on tissue Doppler &gt; 65 ms, as reported by Gorcsan et al<sup>18</sup>; 4) presence of positive criterion of the Saint Mary Hospital score, United Kingdom, as reported by Lane et al<sup>19</sup>; 5) positive criteria for the presence of dyssynchrony, as established by Cleland et al<sup>14</sup>, in the CARE-HF study; 6) standard deviation of the maximum motion times, measured on tissue Doppler maging, in 12 left ventricular segments &gt; 32 ms, proposed by Yu et al<sup>7</sup>; 7) interval values &gt; 60 ms of the onset of mitral ring systolic motion in four segments measured by use of tissue Doppler imaging, as reported by De Sutter et al<sup>20</sup>; 8) interval values &gt; 100 ms of the end of mitral ring systolic motion in four segments measured on tissue Doppler imaging, as reported by Perez de Isla et al<sup>21</sup>, in the Spanish Ventricular Asynchrony Registry - RAVE; 9) interval between the maximum contraction of the anteroseptal and posterior segments &gt; 130 ms measured by use of two-dimensional strain associated with the interval of the septal-to-lateral wall maximum systolic motion on tissue Doppler &gt; 60 ms, as demonstrated by Gorcsan et al<sup>22</sup></p>
      <p>
        <bold>Statistical analysis</bold>
      </p>
      <p>The quantitative variables were described as mean &#177; standard deviation, and the qualitative ones, as percentages. For comparing the different LBBB presentations, the following tests were used: Student t test; Wilcoxon test; chi-square test; and Fisher exact test. The JMP8.0<sup>&#174;</sup> software (Institute Inc. , Carry, North Carolina) was used for calculation. The significance level of 5% was adopted.</p>
      <p>
        <bold>Results</bold>
      </p>
      <p><xref ref-type="table" rid="tab1-body2">Table 1</xref> shows the clinical characteristics of the 48 patients studied, with approximately 90% of them on beta-blockers and angiotensin-converting-enzyme inhibitors/angiotensin-receptor blockers. <xref ref-type="table" rid="tab2-body2">Table 2</xref> shows their electrocardiographic findings. <xref ref-type="table" rid="en_aop5253tab03-body2">Table 3</xref> shows their echocardiographic variables, with varied degrees of intraventricular dyssynchrony according to the criteria used.</p>
      <p content-type="asset">
        <table-wrap id="en_aop5253tab03-body2">
          <graphic xlink:href="1678-4170-abc-101-05-0449-30190-gt01-en.jpg"/></table-wrap>
      </p>
      <table-wrap id="tab1-body2">
        <graphic xlink:href="1678-4170-abc-101-05-0449-30190-gt02-en.jpg"/></table-wrap>
      <table-wrap id="tab2-body2">
        <graphic xlink:href="1678-4170-abc-101-05-0449-30190-gt03-en.jpg"/></table-wrap>
      <p>When patients were compared according to their different LBBB morphologies, QRS duration &gt; 150 ms and electrical axis in the frontal plane -30&#186; did not relate to differences concerning sex, age, history, functional class or medication used, as shown in <xref ref-type="table" rid="en_aop5253tab04-body2">Tables 4</xref> and <xref ref-type="table" rid="en_aop5253tab05-body2">5</xref>.</p>
      <p content-type="asset">
        <table-wrap id="en_aop5253tab04-body2">
          <graphic xlink:href="1678-4170-abc-101-05-0449-30190-gt04-en.jpg"/></table-wrap>
      </p>
      <p content-type="asset">
        <table-wrap id="en_aop5253tab05-body2">
          <graphic xlink:href="1678-4170-abc-101-05-0449-30190-gt05-en.jpg"/></table-wrap>
      </p>
      <p>Regarding echocardiographic findings, patients with QRS duration &gt; 150 ms showed greater left ventricular linear dimensions and volumes, greater left atrial diameters and lower ejection fraction, as shown in <xref ref-type="table" rid="en_aop5253tab04-body2">Table 4</xref>.</p>
      <p>Patients with left electrical axis deviation in the frontal plane, &lt; -30&#186;, showed greater left atrial diameters associated with higher grades of left ventricular diastolic dysfunction, and greater left ventricular diameter, as evidenced in <xref ref-type="table" rid="en_aop5253tab05-body2">Table 5</xref>.</p>
      <p>The presence of interventricular and intraventricular dyssynchrony was similar in the two groups of LBBB (longer QRS interval duration and left electrical axis deviation in the frontal plane) (<xref ref-type="table" rid="en_aop5253tab04-body2">Tables 4</xref> and <xref ref-type="table" rid="en_aop5253tab05-body2">5</xref>).</p>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>The different LBBB presentations assessed do not allow identifying a dyssynchrony pattern, and their prevalences did not differ in the different echocardiographic methodologies assessed.</p>
      <p>However, the LBBB patterns relate to left ventricular morphologic and functional alterations, in which longer QRS complex durations associate with greater left ventricular dimensions, and the left electrical axis deviation on electrocardiogram relates to greater diastolic dysfunction and greater left atrial dimension.</p>
      <p>Those findings are in accordance with the study by Das et al<sup>23</sup>, who have shown that left ventricular ejection fraction is more impaired when the QRS duration is increased in patients with LBBB, but it is not associated with left electrical axis deviation. However, according to Dhingra et al<sup>24</sup>, the higher incidence of events in patients with LBBB and left electrical axis deviation should be associated with greater diastolic dysfunction, which is known to relate to mortality<sup>25</sup>.</p>
      <p>Although not all patients meet the criteria proposed by the last guidelines for implantation of resynchronizing pacemakers<sup>5</sup>, those indications have been modified, and most patients studied constitute a group candidate for CRT, including patients with ejection fraction &lt; 40%<sup>5,26</sup>. Findings might indicate lack of relationship between longer QRS intervals in LBBB and the response to that type of treatment<sup>27</sup>, because the prevalence of mechanical dyssynchrony is similar regardless of the echocardiographic method used.</p>
      <p>Despite the limitations of using echocardiography as the method for selecting candidates for pacemaker implantation with evidenced capacity of resynchronization on the PROSPECT study<sup>28</sup>, most of the methods used proved to distinguish patients who would benefit from that therapy. Single center studies have reported several echocardiographic methods that evidenced a better response to that therapy.</p>
      <p>Sweeney et al<sup>29</sup> have shown that the conventional electrocardiographic report in patients with LBBB, such as QRS duration and the presence of left electrical axis deviation, are not enough to predict individuals who will have echocardiographic improvement after cardiac resynchronization by use of pacemaker. However, electrocardiographic evidence of longer left ventricular activation time and smaller scar volume characterizes the group of patients with a better response to the resynchronizer. Such measures were not assessed in the present study, and the study by Sweeney et al<sup>29</sup> has not compared those electrocardiographic findings with the echocardiographic assessment of mechanical synchrony. That relationship can be tested in a further study.</p>
      <p>
        <bold>Conclusion</bold>
      </p>
      <p>In the two different electrocardiographic patterns of LBBB analyzed with ten echocardiographic methods, no difference regarding the presence of mechanical dyssynchrony was observed. They can, however, be associated with known risk patterns, such as a reduced ejection fraction and greater diastolic dysfunction grades.</p>
      <p>
        <bold>Author contributions</bold>
      </p>
      <p>Conception and design of the research: Barretto RBM, Piegas LS, Moreira DA, Fran&#231;a FF; Acquisition of data: Barretto RBM, Melo Neto JF, Resende TU; Analysis and interpretation of the data: Barretto RBM, Piegas LS, Assef JE, Melo Neto JF, Resende TU, Moreira DA, Fran&#231;a FF; Statistical analysis and Obtaining funding: Barretto RBM; Writing of the manuscript: Barretto RBM, Piegas LS, Assef JE; Critical revision of the manuscript for intellectual content: Barretto RBM, Assef JE, LeBihan DC, Meneghelo RS, Sousa AGMR.</p>
      <p>
        <bold>Potential Conflict of Interest</bold>
      </p>
      <p>No potential conflict of interest relevant to this article was reported.</p>
      <p>
        <bold>Sources of Funding</bold>
      </p>
      <p>There were no external funding sources for this study.</p>
      <p>
        <bold>Study Association</bold>
      </p>
      <p>This article is part of the thesis of doctoral submitted by Rodrigo Bellio de Mattos Barretto, from Universidade de S&#227;o Paulo.</p>
      <p>
        <bold>References</bold>
      </p>
    </body>
  </sub-article>
</article>
