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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</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</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">6ZtnyyqYsRMVRFKGFp65SMx</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2014000300006</article-id>
      <article-id pub-id-type="other">00006</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S0066-782X2014005040003</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20140003</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="pt">Par&#226;metros Ecocardiogr&#225;ficos e Sobrevida na Cardiopatia
               Chag&#225;sica com Disfun&#231;&#227;o Sist&#243;lica Importante</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Rassi</surname>
            <given-names>Daniela do Carmo</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
          <xref ref-type="corresp" rid="c01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Vieira</surname>
            <given-names>Marcelo Luiz Campos</given-names>
          </name>
          <xref ref-type="aff" rid="aff02">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Arruda</surname>
            <given-names>Ana L&#250;cia Martins</given-names>
          </name>
          <xref ref-type="aff" rid="aff03">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Hotta</surname>
            <given-names>Viviane Tiemi</given-names>
          </name>
          <xref ref-type="aff" rid="aff02">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Furtado</surname>
            <given-names>Rog&#233;rio Gomes</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rassi</surname>
            <given-names>Danilo Teixeira</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rassi</surname>
            <given-names>Salvador</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <label>1</label>
        <institution content-type="orgdiv2">Faculdade de Medicina</institution>
        <institution content-type="orgdiv1">Hospital das Cl&#237;nicas</institution>
        <institution content-type="orgname">Universidade Federal de Goi&#225;s</institution>
        <addr-line>
          <named-content content-type="city">Goi&#226;nia</named-content>
          <named-content content-type="state">GO</named-content>
        </addr-line>
        <country>Brasil</country>
        <institution content-type="original">Faculdade de Medicina e Hospital das Cl&#237;nicas da
               Universidade Federal de Goi&#225;s (UFG), Goi&#226;nia, GO - Brasil</institution>
      </aff>
      <aff id="aff02">
        <label>2</label>
        <institution content-type="orgdiv2">Instituto do Cora&#231;&#227;o</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina</institution>
        <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country>Brasil</country>
        <institution content-type="original">Instituto do Cora&#231;&#227;o da Faculdade de Medicina da
               Universidade de S&#227;o Paulo (USP), S&#227;o Paulo, SP - Brasil</institution>
      </aff>
      <aff id="aff03">
        <label>3</label>
        <institution content-type="orgdiv2">Instituto de Radiologia</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina</institution>
        <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country>Brasil</country>
        <institution content-type="original">Instituto de Radiologia da Faculdade de Medicina da
               Universidade de S&#227;o Paulo (USP), S&#227;o Paulo, SP - Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c01"><bold>Correspond&#234;ncia:</bold> Daniela do Carmo Rassi, Rua 1, n&#250;mero 352, apto 901,
               Edif&#237;cio Reserva dos Buritis, Setor Oeste. CEP 74115-040, Goi&#226;nia, GO - Brasil.
               E-mail: <email>dani.rassi@hotmail.com</email>, <email>danirassi@cardiol.br</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa: Rassi DC, Vieira MLC, Arruda ALM, Furtado RG,
                  Rassi DT, Rassi S; Obten&#231;&#227;o de dados: Rassi DC, Rassi DT, Rassi S; An&#225;lise e
                  interpreta&#231;&#227;o dos dados, Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do
                  intelectual e Reda&#231;&#227;o do manuscrito: Rassi DC, Vieira MLC, Arruda ALM, Hotta VT,
                  Furtado RG, Rassi DT, Rassi S; An&#225;lise estat&#237;stica: Rassi DC, Vieira MLC, Arruda
                  ALM, Hotta VT, Furtado RG; Obten&#231;&#227;o de financiamento: Rassi S.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial Conflito de Interesses</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
          </p>
          <p>Este artigo &#233; parte de disserta&#231;&#227;o de Mestrado de Daniela do Carmo Rassi pela
                  Faculdade de Medicina da Universidade Federal de Goi&#225;s (UFG).</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub">
        <day>10</day>
        <month>02</month>
        <year>2014</year>
      </pub-date>
      <pub-date pub-type="collection">
        <month>04</month>
        <year>2014</year>
      </pub-date>
      <volume>102</volume>
      <issue>3</issue>
      <fpage>245</fpage>
      <lpage>252</lpage>
      <history>
        <date date-type="received">
          <day>22</day>
          <month>05</month>
          <year>2013</year>
        </date>
        <date date-type="rev-recd">
          <day>13</day>
          <month>09</month>
          <year>2013</year>
        </date>
        <date date-type="accepted">
          <day>16</day>
          <month>09</month>
          <year>2013</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">
          <license-p>This is an Open Access article distributed under the terms of the Creative
                  Commons Attribution Non-Commercial License which permits unrestricted
                  non-commercial use, distribution, and reproduction in any medium, provided the
                  original work is properly cited. </license-p>
        </license>
      </permissions>
      <abstract xml:lang="pt">
        <sec>
          <title>Fundamento:</title>
          <p> O ecocardiograma fornece dados importantes na avalia&#231;&#227;o cardiol&#243;gica de pacientes
                  em insufici&#234;ncia card&#237;aca. A identifica&#231;&#227;o de par&#226;metros ecocardiogr&#225;ficos na
                  cardiopatia chag&#225;sica grave auxiliaria na implementa&#231;&#227;o terap&#234;utica e na avalia&#231;&#227;o
                  progn&#243;stica. </p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p> Correlacionar par&#226;metros ecocardiogr&#225;ficos com desfecho mortalidade
                  cardiovascular em pacientes com fra&#231;&#227;o de eje&#231;&#227;o &lt; 35%. </p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p> Estudo de an&#225;lise retrospectiva de par&#226;metros ecocardiogr&#225;ficos coletados
                  prospectivamente e pr&#233;-especificados em 60 pacientes inclu&#237;dos no Estudo
                  Multic&#234;ntrico Randomizado de Terapia Celular em Cardiopatias - bra&#231;o cardiopatia
                  chag&#225;sica. Os par&#226;metros foram: di&#226;metros e volumes diast&#243;lico e sist&#243;lico do
                  ventr&#237;culo esquerdo, fra&#231;&#227;o de eje&#231;&#227;o, di&#226;metro do &#225;trio esquerdo, volume do &#225;trio
                  esquerdo, volume indexado do &#225;trio esquerdo, press&#227;o sist&#243;lica da art&#233;ria
                  pulmonar, integral da velocidade do fluxo a&#243;rtico, &#237;ndice de performance
                  mioc&#225;rdica, taxa de aumento da press&#227;o do ventr&#237;culo esquerdo, tempo de
                  relaxamento isovolum&#233;trico, velocidade das ondas E, A, Em, Am e Sm, tempo de
                  desacelera&#231;&#227;o da onda E, rela&#231;&#227;o E/A , E/Em e insufici&#234;ncia mitral. </p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p> No seguimento m&#233;dio de 24,18 meses, 27 pacientes faleceram. a fra&#231;&#227;o de eje&#231;&#227;o
                  m&#233;dia era de 26,6 &#177; 5,34%. Na an&#225;lise multivariada, foram inclu&#237;dos os par&#226;metros
                  de fra&#231;&#227;o de eje&#231;&#227;o (HR = 1,114; p = 0,3704), volume indexado do &#225;trio esquerdo
                  (HR = 1,033; p &lt; 0,0001) e rela&#231;&#227;o E/Em (HR = 0,95; p = 0,1261). O volume
                  indexado do &#225;trio esquerdo foi um fator de predi&#231;&#227;o independente em rela&#231;&#227;o ao
                  desfecho e observou-se que um valor &gt; 70,71 mL/m<sup>2</sup> foi associado ao
                  aumento significativo na mortalidade (log rank p &lt; 0,0001). </p>
        </sec>
        <sec>
          <title>Conclus&#227;o:</title>
          <p> O volume indexado do &#225;trio esquerdo mostrou-se como &#250;nico fator de predi&#231;&#227;o
                  independente de mortalidade nesta popula&#231;&#227;o de pacientes chag&#225;sicos e com
                  disfun&#231;&#227;o sist&#243;lica importante.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <kwd>Ecocardiografia / diagn&#243;stico</kwd>
        <kwd>Sobrevida</kwd>
        <kwd>Cardiomiopatia Chag&#225;sica</kwd>
        <kwd>Doen&#231;a de Chagas</kwd>
      </kwd-group>
      <funding-group>
        <award-group>
          <funding-source>FINEP</funding-source>
        </award-group>
      </funding-group>
      <counts>
        <fig-count count="3"/>
        <table-count count="4"/>
        <equation-count count="0"/>
        <ref-count count="22"/>
        <page-count count="8"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>Ap&#243;s 100 anos de sua descoberta, a doen&#231;a de Chagas permanece um problema grave de sa&#250;de
            e economia na maioria dos pa&#237;ses da Am&#233;rica Latina. Estima-se que 10 milh&#245;es de pessoas
            est&#227;o infectadas no mundo, a maioria na Am&#233;rica Latina, onde a doen&#231;a &#233; end&#234;mica. Mais
            de 25 milh&#245;es de pessoas est&#227;o sob risco da doen&#231;a. A doen&#231;a de Chagas matou mais de 10
            mil pessoas em uma estimativa realizada em 2008<xref ref-type="bibr" rid="B01">1</xref>.</p>
      <p>Essa doen&#231;a parasit&#225;ria &#233; transmitida ao homem por meio de fezes infectadas de insetos
            hemat&#243;fagos em &#225;reas end&#234;micas e, ocasionalmente, por transfus&#227;o sangu&#237;nea, e o seu
            diagn&#243;stico &#233; realizado por uma hist&#243;ria sugestiva de contato e dois ou mais testes
            sorol&#243;gicos espec&#237;ficos positivos<xref ref-type="bibr" rid="B02">2</xref>
				<sup>,</sup>
				<xref ref-type="bibr" rid="B03">3</xref>.</p>
      <p>A doen&#231;a de Chagas possui duas fases: aguda e cr&#244;nica. A fase aguda comumente
            manifesta-se como uma s&#237;ndrome febril autolimitada, que dura de 2 a 8 semanas com
            manifesta&#231;&#245;es cl&#237;nicas em menos de 1% dos pacientes. Na fase cr&#244;nica, aproximadamente
            metade desses pacientes permanece na forma indeterminada, que possui baixa morbidade e
            bom progn&#243;stico, enquanto que a outra metade evolui para a forma cr&#244;nica, com
            comprometimento card&#237;aco e/ou digestivo ap&#243;s 10 a 30 anos da infec&#231;&#227;o inicial<xref ref-type="bibr" rid="B02">2</xref>
				<sup>,</sup>
				<xref ref-type="bibr" rid="B04">4</xref>
				<sup>,</sup>
				<xref ref-type="bibr" rid="B05">5</xref>.</p>
      <p>A forma card&#237;aca &#233; a manifesta&#231;&#227;o mais frequente e grave da doen&#231;a de Chagas em sua fase
            cr&#244;nica. As altera&#231;&#245;es mioc&#225;rdicas na fase cr&#244;nica s&#227;o extremamente vari&#225;veis. V&#227;o desde
            formas discretas, como os aneurismas digitiformes apicais e altera&#231;&#245;es somente na fun&#231;&#227;o
            diast&#243;lica do ventr&#237;culo esquerdo, at&#233; dilata&#231;&#245;es importantes das cavidades card&#237;acas,
            com disfun&#231;&#227;o sist&#243;lica importante<xref ref-type="bibr" rid="B05">5</xref>
				<sup>-</sup>
				<xref ref-type="bibr" rid="B08">8</xref>.</p>
      <p>O ecocardiograma &#233; um exame j&#225; bem estabelecido na pr&#225;tica cl&#237;nica e com par&#226;metros que
            podem analisar e estratificar os pacientes chag&#225;sicos. Em nosso estudo, foram avaliados
            pacientes com disfun&#231;&#227;o sist&#243;lica importante, que j&#225; possuem um progn&#243;stico reservado.
            Nosso objetivo foi identificar os par&#226;metros de mau progn&#243;stico, que nos possibilitariam
            instituir um tratamento mais agressivo e otimizado, na tentativa de melhorar a evolu&#231;&#227;o
            desfavor&#225;vel desses pacientes<xref ref-type="bibr" rid="B09">9</xref>
				<sup>,</sup>
				<xref ref-type="bibr" rid="B10">10</xref>.</p>
    </sec>
    <sec sec-type="methods">
      <title>M&#233;todos</title>
      <sec>
        <title>Popula&#231;&#227;o e local do estudo</title>
        <p>Este foi um estudo de an&#225;lise retrospectiva dos dados coletados prospectivamente e
               pr&#233;-especificados de pacientes inclu&#237;dos no Estudo Multic&#234;ntrico Randomizado de
               Terapia Celular em Cardiopatias (EMRTCC) - bra&#231;o cardiopatia chag&#225;sica, realizado no
               per&#237;odo de fevereiro de 2006 a fevereiro de 2009. O EMRTCC foi um estudo prospectivo,
               randomizado, duplo-cego, que, em nossa institui&#231;&#227;o, teve uma amostra de 60 pacientes
               com disfun&#231;&#227;o sist&#243;lica importante (Fra&#231;&#227;o de Eje&#231;&#227;o - FE &lt; 35%) e em classes
               funcionais III e IV (NYHA). Os crit&#233;rios de exclus&#227;o foram doen&#231;as valvares, exceto
               insufici&#234;ncia funcional mitral ou tric&#250;spide; coronariografia mostrando les&#227;o
               significativa (50% ou mais de obstru&#231;&#227;o em uma ou mais coron&#225;rias); presen&#231;a de
               cardioversor/desfibrilador implant&#225;vel em funcionamento; doen&#231;as que pudessem ter
               impacto na expectativa de vida ou qualquer outra comorbidade com impacto na sobrevida
               em 2 anos; e imagem ecocardiogr&#225;fica inadequada para sua correta interpreta&#231;&#227;o. Foram
               realizadas as medidas ecocardiogr&#225;ficas quando da randomiza&#231;&#227;o dos pacientes. Nessa
               ocasi&#227;o, a otimiza&#231;&#227;o do tratamento cl&#237;nico havia sido alcan&#231;ada, e os pacientes se
               encontravam hemodinamicamente est&#225;veis. O resultado do estudo EMRTCC - bra&#231;o
               cardiopatia chag&#225;sica n&#227;o mostrou eleva&#231;&#227;o da FE no grupo que recebeu implante de
               c&#233;lul tronco, sendo considerada homog&#234;nea a popula&#231;&#227;o de 60 pacientes, sem influ&#234;ncia
               da interven&#231;&#227;o entre os dois grupos<xref ref-type="bibr" rid="B11">11</xref>.</p>
        <p>O desfecho prim&#225;rio de nosso estudo foi definido como mortalidade cardiovascular.
               Considerou-se como mortalidade cardiovascular a morte s&#250;bita, quando esta ocorreu em
               menos de 1 hora da mudan&#231;a dos sintomas, ou como morte por piora progressiva da
               insufici&#234;ncia card&#237;aca, quando esta se deu por piora dos sintomas ou deteriora&#231;&#227;o
               hemodin&#226;mica pr&#233;via.</p>
        <p>O estudo foi realizado no Hospital das Cl&#237;nicas da Universidade Federal de Goi&#225;s
               (HC-UFG). Os pacientes foram selecionados do ambulat&#243;rio de Insufici&#234;ncia Card&#237;aca da
               institui&#231;&#227;o. As avalia&#231;&#245;es cl&#237;nicas e o seguimento desses pacientes foram realizados
               neste ambulat&#243;rio. O ecocardiograma foi realizado no servi&#231;o de imagem da
               institui&#231;&#227;o. O projeto foi aprovado pela Comiss&#227;o Cient&#237;fica e de &#201;tica do HC-UFG e
               os pacientes assinaram o Termo de Consentimento Livre e Esclarecido.</p>
      </sec>
      <sec>
        <title>Avalia&#231;&#227;o ecocardiogr&#225;fica</title>
        <p>Os ecocardiogramas foram realizados no aparelho Xsario (Toshiba), dispon&#237;vel do setor
               de ecocardiografia do HC UFG, com imagens gravadas digitalmente. As imagens foram
               obtidas de acordo com os crit&#233;rios estabelecidos pela <italic>American Society of
                  Echocardiography</italic> (ASE)<xref ref-type="bibr" rid="B12">12</xref>. Todos os
               exames foram realizados por um &#250;nico examinador, com ampla experi&#234;ncia em sua
               realiza&#231;&#227;o, devidamente treinado para a obten&#231;&#227;o dos par&#226;metros mensurados e em um
               &#250;nico aparelho da institui&#231;&#227;o.</p>
        <p>Foram avaliados os seguintes par&#226;metros do estudo ecocardiogr&#225;fico: di&#226;metro
               diast&#243;lico final do ventr&#237;culo esquerdo (DDFVE) e di&#226;metro sist&#243;lico final do VE
               (DSFVE), volume diast&#243;lico final do VE (VDFVE) e volume sist&#243;lico final do VE
               (VSFVE), FE estimada pelo m&#233;todo de Simpson, di&#226;metro do &#225;trio esquerdo (AE), volume
               do AE (VAE), VAE indexado para a superf&#237;cie corp&#243;rea (VAE/m<sup>2</sup>), press&#227;o
               sist&#243;lica da art&#233;ria pulmonar (PSAP), integral da velocidade do fluxo a&#243;rtico (VTI
               Ao), derivada de press&#227;o/derivada de tempo (dP/dT), tempo de relaxamento
               isovolum&#233;trico (TRIV), &#237;ndice de <italic>performance</italic> mioc&#225;rdica (IPM),
               velocidade das ondas E e A (por meio do Doppler pulsado), rela&#231;&#227;o E/A e tempo de
               desacelera&#231;&#227;o da onda E (TDA), velocidade tecidual mioc&#225;rdica das ondas Em, Am e Sm
               (por meio do Doppler tecidual no segmento basal da parede septal inferior), rela&#231;&#227;o
               das ondas E/Em.</p>
      </sec>
      <sec>
        <title>An&#225;lise estat&#237;stica</title>
        <p>As curvas de sobrevida foram calculadas com o m&#233;todo produto-limite de Kapplan-Meier
               e comparadas com o teste log-rank. Probabilidades de sobrevida foram estimadas com
               Intervalo de Confian&#231;a (IC) de 95%. Vari&#225;veis quantitativas foram dicotomizadas
               utilizando se o ponto de corte &#243;timo obtido de an&#225;lises ROC (sigla do ingl&#234;s
                  <italic>Receive Operatoring Characteristic</italic>). Raz&#245;es de Risco (RR) n&#227;o
               ajustada e ajustada com IC95% foram estimadas nas an&#225;lises de regress&#227;o univariada e
               multivariada de Cox, respectivamente. O modelo de regress&#227;o m&#250;ltipla utilizou a
               propor&#231;&#227;o de n&#250;mero de eventos por vari&#225;vel de 9/1, com estabilidade confirmada das
               estimativas. Normalidade de vari&#225;veis foi avaliada com teste de Kolmogorov-Smirnov,
               sendo representadas como m&#233;dia &#177; desvio padr&#227;o ou mediana e IC95%, dependendo da
               distribui&#231;&#227;o normal ou n&#227;o normal, respectivamente. Todas as probabilidades de
               signific&#226;ncia (valores de p) apresentadas s&#227;o do tipo bilateral e valores &lt; 0,05
               foram considerados estatisticamente significantes. Valores de p entre 0,05 e 0,10
               foram interpretados como marginalmente significantes. A an&#225;lise estat&#237;stica dos dados
               foi efetuada utilizando-se os <italic>softwares</italic> Stata 11 (Stata Corp,
               College Station, TX) e SAS 9.2 (Statistical Analysis System, Cary, NC).</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Resultados</title>
      <p>As caracter&#237;sticas cl&#237;nicas e ecocardiogr&#225;ficas do grupo estudado est&#227;o demonstradas nas
               <xref ref-type="table" rid="t01">Tabelas 1</xref> e <xref ref-type="table" rid="t02">2</xref>, respectivamente.</p>
      <table-wrap id="t01">
        <label>Tabela 1</label>
        <caption>
          <title>Caracter&#237;sticas cl&#237;nicas do grupo</title>
        </caption>
        <table rules="rows" frame="hsides">
          <thead>
            <tr>
              <td>
                <bold>Caracter&#237;stica</bold>
              </td>
              <td align="center">
                <bold>M&#233;dia &#177; DP</bold>
              </td>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td>Idade (anos)</td>
              <td align="center">50,9 &#177; 9,3</td>
            </tr>
            <tr>
              <td>Sexo(%)</td>
              <td align="center">n = 60</td>
            </tr>
            <tr>
              <td>Masculino</td>
              <td align="center">70</td>
            </tr>
            <tr>
              <td>Tratamento medicamentoso (%)</td>
              <td align="center">n = 60</td>
            </tr>
            <tr>
              <td>Diur&#233;tico</td>
              <td align="center">88,3</td>
            </tr>
            <tr>
              <td>IECA</td>
              <td align="center">60</td>
            </tr>
            <tr>
              <td>BRA</td>
              <td align="center">21</td>
            </tr>
            <tr>
              <td>Betabloqueador</td>
              <td align="center">60</td>
            </tr>
            <tr>
              <td>Espironolactona</td>
              <td align="center">85</td>
            </tr>
            <tr>
              <td>Digoxina</td>
              <td align="center">61</td>
            </tr>
            <tr>
              <td>Amiodarona</td>
              <td align="center">58,33</td>
            </tr>
            <tr>
              <td>Ritmo de fibrila&#231;&#227;o atrial (%)</td>
              <td align="center">6,6</td>
            </tr>
            <tr>
              <td>Marca-passo (%)</td>
              <td align="center">30</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn>
            <p>DP: desvio padr&#227;o; IECA: enzima conversora da angiotensina; BRA: bloqueador do
                     receptor de angiotensina II.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <table-wrap id="t02">
        <label>Tabela 2</label>
        <caption>
          <title>Caracter&#237;sticas ecocardiogr&#225;ficas do grupo</title>
        </caption>
        <table rules="rows" frame="hsides">
          <thead>
            <tr>
              <td rowspan="2">
                <bold>Vari&#225;vel</bold>
              </td>
              <td rowspan="2" align="center">
                <bold>P (KS)</bold>
              </td>
              <td colspan="3" align="center">
                <bold>Par&#226;metros</bold>
              </td>
            </tr>
            <tr>
              <td align="center">
                <bold>M&#233;dia &#177; DP</bold>
              </td>
              <td align="center">
                <bold>Mediana</bold>
              </td>
              <td align="center">
                <bold>IC 95%</bold>
              </td>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td>FE (%)</td>
              <td align="center">0,617</td>
              <td align="center">26,7 &#177; 5,3</td>
              <td align="center">27,4</td>
              <td align="center">25,3 - 28,1</td>
            </tr>
            <tr>
              <td>DDFVE (mm)</td>
              <td align="center">0,667</td>
              <td align="center">78,9 &#177; 8,7</td>
              <td align="center">78,6</td>
              <td align="center">76,7 - 81,2</td>
            </tr>
            <tr>
              <td>DSFVE (mm)</td>
              <td align="center">0,485</td>
              <td align="center">67,4 &#177; 8,0</td>
              <td align="center">67,3</td>
              <td align="center">65,3 - 69,5</td>
            </tr>
            <tr>
              <td>VDFVE (mL)</td>
              <td align="center">0,724</td>
              <td align="center">271,3 &#177; 94,5</td>
              <td align="center">265,6</td>
              <td align="center">246,9 - 295,7</td>
            </tr>
            <tr>
              <td>VSFVE (mL)</td>
              <td align="center">0,855</td>
              <td align="center">189,3 &#177; 73,0</td>
              <td align="center">186,8</td>
              <td align="center">170,5 - 208,2</td>
            </tr>
            <tr>
              <td>AE (mm)</td>
              <td align="center">0,833</td>
              <td align="center">48,3 &#177; 8,5</td>
              <td align="center">48,0</td>
              <td align="center">46,1 - 50,5</td>
            </tr>
            <tr>
              <td>VAE (mL)</td>
              <td align="center">0,375</td>
              <td align="center">104,9 &#177; 42,3</td>
              <td align="center">98,7</td>
              <td align="center">93,9 - 115,8</td>
            </tr>
            <tr>
              <td>VAE/m<sup>2</sup> (ml/m<sup>2</sup>)</td>
              <td align="center">0,330</td>
              <td align="center">62,9 &#177; 24,4</td>
              <td align="center">58,8</td>
              <td align="center">56,6 - 69,2</td>
            </tr>
            <tr>
              <td>PSAP (mmHg)</td>
              <td align="center">0,022<xref ref-type="table-fn" rid="t02-fn01">*</xref>
							</td>
              <td align="center">38,1 &#177; 13,4</td>
              <td align="center">33,6</td>
              <td align="center">34,3 - 41,9</td>
            </tr>
            <tr>
              <td>VTI Ao (cm)</td>
              <td align="center">0,002<xref ref-type="table-fn" rid="t02-fn01">*</xref>
							</td>
              <td align="center">13,2 &#177; 8,7</td>
              <td align="center">12,0</td>
              <td align="center">10,9 - 15,5</td>
            </tr>
            <tr>
              <td>TDA (ms)</td>
              <td align="center">0,122</td>
              <td align="center">188,0 &#177; 92,3</td>
              <td align="center">160,0</td>
              <td align="center">164,2 - 211,8</td>
            </tr>
            <tr>
              <td>IPM</td>
              <td align="center">0,026<xref ref-type="table-fn" rid="t02-fn01">*</xref>
							</td>
              <td align="center">0,89 &#177; 0,40</td>
              <td align="center">0,82</td>
              <td align="center">0,79 - 0,99</td>
            </tr>
            <tr>
              <td>dP/dT</td>
              <td align="center">0,286</td>
              <td align="center">489,6 &#177; 162,3</td>
              <td align="center">444,0</td>
              <td align="center">447,7 - 531,5</td>
            </tr>
            <tr>
              <td>TRIV (ms)</td>
              <td align="center">0,005<xref ref-type="table-fn" rid="t02-fn01">*</xref>
							</td>
              <td align="center">116,9 &#177; 72,1</td>
              <td align="center">100,0</td>
              <td align="center">98,3 - 135,6</td>
            </tr>
            <tr>
              <td>A (cm/s)</td>
              <td align="center">0,426</td>
              <td align="center">46,8 &#177; 23,3</td>
              <td align="center">41,3</td>
              <td align="center">40,5 - 53,1</td>
            </tr>
            <tr>
              <td>E (cm/s)</td>
              <td align="center">0,522</td>
              <td align="center">63,9 &#177; 25,0</td>
              <td align="center">61,4</td>
              <td align="center">57,5 - 70,4</td>
            </tr>
            <tr>
              <td>Am (cm/s)</td>
              <td align="center">0,853</td>
              <td align="center">4,8 &#177; 2,1</td>
              <td align="center">4,5</td>
              <td align="center">4,3 - 5,4</td>
            </tr>
            <tr>
              <td>Em (cm/s)</td>
              <td align="center">0,395</td>
              <td align="center">4,8 &#177; 1,7</td>
              <td align="center">4,5</td>
              <td align="center">4,4 - 5,3</td>
            </tr>
            <tr>
              <td>Sm (cm/s)</td>
              <td align="center">0,774</td>
              <td align="center">4,6 &#177; 1,2</td>
              <td align="center">4,7</td>
              <td align="center">4,3 - 4,9</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="t02-fn01">
            <label>*</label>
            <p> Significativo: vari&#225;veis que n&#227;o apresentam distribui&#231;&#227;o normal. KS: teste da
                     normalidade de Kolmogorov-Smirnov; DP: desvio padr&#227;o; IC95%: intervalo de
                     confian&#231;a de 95%; FE: fra&#231;&#227;o de eje&#231;&#227;o; DDFVE: di&#226;metro diast&#243;lico final do
                     ventr&#237;culo esquerdo; DSFVE: di&#226;metro sist&#243;lico final do ventr&#237;culo esquerdo;
                     VDFVE: volume diast&#243;lico final do ventr&#237;culo esquerdo; VSFVE: volume sist&#243;lico
                     final do ventr&#237;culo esquerdo; AE: medida anteroposterior do &#225;trio esquerdo;
                     VAE: volume do &#225;trio esquerdo; VAE/m<sup>2</sup>: volume do &#225;trio esquerdo
                     indexado para a superf&#237;cie corp&#243;rea; PSAP: press&#227;o sist&#243;lica da art&#233;ria
                     pulmonar; VTI Ao: integral da velocidade do fluxo a&#243;rtico; TDA: tempo de
                     desacelera&#231;&#227;o da onda E; IPM: &#237;ndice de performance mioc&#225;rdica; dP/dT: derivada
                     de press&#227;o/derivada de tempo; TRIV: tempo de relaxamento isovolum&#233;trico; A:
                     velocidade transmitral do enchimento ventricular tardio; E: velocidade
                     transmitral do enchimento ventricular precoce; Em e Am: velocidades teciduais
                     diast&#243;licas; Sm: velocidade tecidual sist&#243;lica.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>Morte de causa cardiovascular ocorreu em 27 (45%) dos 60 pacientes em seguimento m&#233;dio
            de 24 meses (<xref ref-type="fig" rid="f01">Figura 1</xref>). Todos mantiveram
            tratamento medicamentoso otimizado e n&#227;o receberam terapia de ressincroniza&#231;&#227;o ou
            cardiodesfibrilador implant&#225;vel durante o seguimento.</p>
      <fig id="f01" fig-type="other">
        <label>Figura 1</label>
        <caption>
          <title>Curva de Kapplan-Meier com an&#225;lise de sobrevida geral na popula&#231;&#227;o do
                  estudo.</title>
        </caption>
        <graphic xlink:href="1678-4170-abc-102-03-0245-40003-gf01.jpg"/></fig>
      <sec>
        <title>An&#225;lise dos par&#226;metros ecocardiogr&#225;ficos</title>
        <p>A associa&#231;&#227;o entre os par&#226;metros ecocardiogr&#225;ficos e o desfecho foi inicialmente
               avaliada pela an&#225;lise univariada (<xref ref-type="table" rid="t03">Tabela
               3</xref>).</p>
        <table-wrap id="t03">
          <label>Tabela 3</label>
          <caption>
            <title>An&#225;lise univariada dos fatores de predi&#231;&#227;o de eventos
                     cardiovasculares</title>
          </caption>
          <table rules="rows" frame="hsides">
            <thead>
              <tr>
                <td>
                  <bold>Par&#226;metro</bold>
                </td>
                <td align="center">
                  <bold> n</bold>
                </td>
                <td align="center">
                  <bold>Eventos</bold>
                </td>
                <td align="center">
                  <bold>HR</bold>
                </td>
                <td align="center">
                  <bold>IC 95% mais baixo</bold>
                </td>
                <td align="center">
                  <bold>IC 95% mais alto</bold>
                </td>
                <td align="center">
                  <bold>Valor de p</bold>
                </td>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>FE</td>
                <td align="center">60</td>
                <td align="center">27</td>
                <td align="center">0,932</td>
                <td align="center">0,873</td>
                <td align="center">0,994</td>
                <td align="center">0,031<xref ref-type="table-fn" rid="t03-fn01">*</xref>
								</td>
              </tr>
              <tr>
                <td>DDFVE</td>
                <td align="center">60</td>
                <td align="center">27</td>
                <td align="center">1,036</td>
                <td align="center">0,988</td>
                <td align="center">1,087</td>
                <td align="center">0,1464</td>
              </tr>
              <tr>
                <td>DSFVE</td>
                <td align="center">60</td>
                <td align="center">27</td>
                <td align="center">2,573</td>
                <td align="center">0,972</td>
                <td align="center">6,81</td>
                <td align="center">0,057</td>
              </tr>
              <tr>
                <td>VDFVE</td>
                <td align="center">60</td>
                <td align="center">27</td>
                <td align="center">1,005</td>
                <td align="center">1,001</td>
                <td align="center">1,009</td>
                <td align="center">0,0275<xref ref-type="table-fn" rid="t03-fn01">*</xref>
								</td>
              </tr>
              <tr>
                <td>VSFVE</td>
                <td align="center">60</td>
                <td align="center">27</td>
                <td align="center">1,005</td>
                <td align="center">1</td>
                <td align="center">1,01</td>
                <td align="center">0,0403<xref ref-type="table-fn" rid="t03-fn01">*</xref>
								</td>
              </tr>
              <tr>
                <td>AE</td>
                <td align="center">60</td>
                <td align="center">27</td>
                <td align="center">1,064</td>
                <td align="center">1,021</td>
                <td align="center">1,109</td>
                <td align="center">0,0031<xref ref-type="table-fn" rid="t03-fn01">*</xref>
								</td>
              </tr>
              <tr>
                <td>VAE</td>
                <td align="center">60</td>
                <td align="center">27</td>
                <td align="center">1,015</td>
                <td align="center">1,008</td>
                <td align="center">1,021</td>
                <td align="center">&lt; 0,0001<xref ref-type="table-fn" rid="t03-fn01">*</xref>
								</td>
              </tr>
              <tr>
                <td>VAE/m<sup>2</sup>
								</td>
                <td align="center">60</td>
                <td align="center">24</td>
                <td align="center">1,036</td>
                <td align="center">1,021</td>
                <td align="center">1,051</td>
                <td align="center">&lt; 0,0001<xref ref-type="table-fn" rid="t03-fn01">*</xref>
								</td>
              </tr>
              <tr>
                <td>PSAP</td>
                <td align="center">50</td>
                <td align="center">27</td>
                <td align="center">1,039</td>
                <td align="center">1,012</td>
                <td align="center">1,067</td>
                <td align="center">0,0039<xref ref-type="table-fn" rid="t03-fn01">*</xref>
								</td>
              </tr>
              <tr>
                <td>VTI Ao</td>
                <td align="center">59</td>
                <td align="center">26</td>
                <td align="center">0,947</td>
                <td align="center">0,852</td>
                <td align="center">1,053</td>
                <td align="center">0,3151</td>
              </tr>
              <tr>
                <td>TDA</td>
                <td align="center">60</td>
                <td align="center">27</td>
                <td align="center">0,993</td>
                <td align="center">0,987</td>
                <td align="center">0,998</td>
                <td align="center">0,0093<xref ref-type="table-fn" rid="t03-fn01">*</xref>
								</td>
              </tr>
              <tr>
                <td>IPM</td>
                <td align="center">60</td>
                <td align="center">27</td>
                <td align="center">2,423</td>
                <td align="center">1,032</td>
                <td align="center">5,689</td>
                <td align="center">0,0421<xref ref-type="table-fn" rid="t03-fn01">*</xref>
								</td>
              </tr>
              <tr>
                <td>dP/dT</td>
                <td align="center">60</td>
                <td align="center">27</td>
                <td align="center">1</td>
                <td align="center">0,998</td>
                <td align="center">1,003</td>
                <td align="center">0,7342</td>
              </tr>
              <tr>
                <td>TRIV</td>
                <td align="center">60</td>
                <td align="center">27</td>
                <td align="center">0,997</td>
                <td align="center">0,99</td>
                <td align="center">1,004</td>
                <td align="center">0,3499</td>
              </tr>
              <tr>
                <td>A</td>
                <td align="center">56</td>
                <td align="center">23</td>
                <td align="center">0,976</td>
                <td align="center">0,956</td>
                <td align="center">0,996</td>
                <td align="center">0,0212<xref ref-type="table-fn" rid="t03-fn01">*</xref>
								</td>
              </tr>
              <tr>
                <td>E</td>
                <td align="center">60</td>
                <td align="center">27</td>
                <td align="center">1,029</td>
                <td align="center">1,013</td>
                <td align="center">1,046</td>
                <td align="center">0,0004<xref ref-type="table-fn" rid="t03-fn01">*</xref>
								</td>
              </tr>
              <tr>
                <td>E/A</td>
                <td align="center">56</td>
                <td align="center">23</td>
                <td align="center">1,589</td>
                <td align="center">1,205</td>
                <td align="center">2,096</td>
                <td align="center">0,001<xref ref-type="table-fn" rid="t03-fn01">*</xref>
								</td>
              </tr>
              <tr>
                <td>Am</td>
                <td align="center">56</td>
                <td align="center">23</td>
                <td align="center">0,847</td>
                <td align="center">0,687</td>
                <td align="center">1,044</td>
                <td align="center">0,1192</td>
              </tr>
              <tr>
                <td>Em</td>
                <td align="center">60</td>
                <td align="center">27</td>
                <td align="center">1,003</td>
                <td align="center">0,805</td>
                <td align="center">1,249</td>
                <td align="center">0,9815</td>
              </tr>
              <tr>
                <td>Sm</td>
                <td align="center">60</td>
                <td align="center">27</td>
                <td align="center">0,726</td>
                <td align="center">0,514</td>
                <td align="center">1,026</td>
                <td align="center">0,07<xref ref-type="table-fn" rid="t03-fn01">*</xref>
								</td>
              </tr>
              <tr>
                <td>E/ EM</td>
                <td align="center">59</td>
                <td align="center">27</td>
                <td align="center">1,083</td>
                <td align="center">1,019</td>
                <td align="center">1,151</td>
                <td align="center">0,0104<xref ref-type="table-fn" rid="t03-fn01">*</xref>
								</td>
              </tr>
              <tr>
                <td>IM 1 vs. 2</td>
                <td align="center">60</td>
                <td align="center">27</td>
                <td align="center">0,325</td>
                <td align="center">0,146</td>
                <td align="center">0,728</td>
                <td align="center">0,0063<xref ref-type="table-fn" rid="t03-fn01">*</xref>
								</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="t03-fn01">
              <label>*</label>
              <p> Significativo: vari&#225;veis estatisticamente significantes; HR: hazard ratio;
                        IC95%: intervalo de confian&#231;a de 95%; RR: raz&#227;o de risco; IC95%: intervalo
                        de confian&#231;a de 95%; FE: fra&#231;&#227;o de eje&#231;&#227;o; DDFVE: di&#226;metro diast&#243;lico final
                        do ventr&#237;culo esquerdo; DSFVE: di&#226;metro sist&#243;lico final do ventr&#237;culo
                        esquerdo; VDFVE: volume diast&#243;lico final do ventr&#237;culo esquerdo; VSFVE:
                        volume sist&#243;lico final do ventr&#237;culo esquerdo; AE: medida anteroposterior do
                        &#225;trio esquerdo; VAE: volume do &#225;trio esquerdo; VAE/m<sup>2</sup>: volume do
                        &#225;trio esquerdo indexado para a superf&#237;cie corp&#243;rea; PSAP: press&#227;o sist&#243;lica
                        da art&#233;ria pulmonar; VTI Ao: integral da velocidade do fluxo a&#243;rtico; TDA:
                        tempo de desacelera&#231;&#227;o da onda E; IPM: &#237;ndice de performance mioc&#225;rdica;
                        dP/dT: derivada de press&#227;o/derivada de tempo; TRIV: tempo de relaxamento
                        isovolum&#233;trico; A: velocidade transmitral do enchimento ventricular tardio;
                        E: velocidade transmitral do enchimento ventricular precoce; E/A: rela&#231;&#227;o
                        das ondas E e A; Em e Am: velocidades teciduais diast&#243;licas; Sm: velocidade
                        tecidual sist&#243;lica; E/Em: rela&#231;&#227;o das ondas E e Em; IM 1 vs. 2:
                        insufici&#234;ncia mitral discreta versus moderada.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Baseado na relev&#226;ncia cl&#237;nica e buscando a inclus&#227;o de dados anat&#244;micos e funcionais,
               foram selecionados para a an&#225;lise multivariada tr&#234;s par&#226;metros ecocardiogr&#225;ficos
                  (<xref ref-type="table" rid="t04">Tabela 4</xref>).</p>
        <table-wrap id="t04">
          <label>Tabela 4</label>
          <caption>
            <title>An&#225;lise multivariada dos fatores de predi&#231;&#227;o de eventos
                     cardiovasculares</title>
          </caption>
          <table rules="rows" frame="hsides">
            <thead>
              <tr>
                <td>
                  <bold>Par&#226;metro </bold>
                </td>
                <td align="center">
                  <bold>Coeficiente de regress&#227;o (beta)</bold>
                </td>
                <td align="center">
                  <bold>HR</bold>
                </td>
                <td align="center">
                  <bold>IC 95% mais baixo</bold>
                </td>
                <td align="center">
                  <bold>IC 95% mais alto</bold>
                </td>
                <td align="center">
                  <bold>Valor de p</bold>
                </td>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>FE</td>
                <td align="center">-0,0508945</td>
                <td align="center">0,95</td>
                <td align="center">0,89</td>
                <td align="center">1,014</td>
                <td align="center">0,1261</td>
              </tr>
              <tr>
                <td>VAE/m<sup>2</sup>
								</td>
                <td align="center">0,0321653</td>
                <td align="center">1,033</td>
                <td align="center">1,017</td>
                <td align="center">1,049</td>
                <td align="center">&lt; 0,0001<xref ref-type="table-fn" rid="t04-fn01">*</xref>
								</td>
              </tr>
              <tr>
                <td>E/Em</td>
                <td align="center"> 0,0337537</td>
                <td align="center">1,034</td>
                <td align="center">0,961</td>
                <td align="center">1,114</td>
                <td align="center">0,3704</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="t04-fn01">
              <label>*</label>
              <p> Significativo: vari&#225;veis estatisticamente significantes; HR: hazard ratio;
                        IC95%: intervalo de confian&#231;a de 95%; RR: raz&#227;o de risco; IC95%: intervalo
                        de confian&#231;a de 95%; FE: fra&#231;&#227;o de eje&#231;&#227;o; VAE/m': volume do &#225;trio esquerdo
                        indexado para a superf&#237;cie corp&#243;rea; E/Em: rela&#231;&#227;o das ondas E (velocidade
                        transmitral do enchimento) e Em (velocidade tecidual diast&#243;lica).</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Dentre os par&#226;metros avaliados, somente o VAE mL/m<sup>2</sup> apresentou-se como
               fator de predi&#231;&#227;o independente em rela&#231;&#227;o ao desfecho.</p>
        <p>Quando obtido um valor para o VAE/m<sup>2</sup> de 70,71 mL/m<sup>2</sup>,
               observou-se um maior distanciamento entre a popula&#231;&#227;o estudada em rela&#231;&#227;o ao desfecho
               mortalidade (<xref ref-type="fig" rid="f02">Figura 2</xref>), com uma &#225;rea sob a
               curva de 0,827 (IC95% = 0,708 - 0,913) (<xref ref-type="fig" rid="f03">Figura
                  3</xref>).</p>
        <fig id="f02" fig-type="other">
          <label>Figura 2</label>
          <caption>
            <title>Demonstra rela&#231;&#227;o entre a sobrevida e o volume indexado do &#225;trio esquerdo
                     (VAE /m<sup>2</sup>).</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-102-03-0245-40003-gf02.jpg"/></fig>
        <fig id="f03" fig-type="other">
          <label>Figura 3</label>
          <caption>
            <title>Demostra a curva ROC do volume indexado do &#225;trio esquerdo.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-102-03-0245-40003-gf03.jpg"/></fig>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discuss&#227;o</title>
      <p>A maioria dos estudos ecocardiogr&#225;ficos envolvendo pacientes com cardiomiopatia
            chag&#225;sica cr&#244;nica procurou correlacionar par&#226;metros ecocardiogr&#225;ficos com sobrevida,
            utilizando modelos de risco proporcional (modelos de COX). As popula&#231;&#245;es avaliadas
            nesses estudos possu&#237;am vari&#225;vel express&#227;o da doen&#231;a, que ia desde nenhum
            comprometimento card&#237;aco at&#233; doen&#231;a grave, com sintomas importantes. Em nosso estudo
            foram selecionados exclusivamente pacientes que apresentavam comprometimento estrutural
            card&#237;aco de grande magnitude e com disfun&#231;&#227;o sist&#243;lica importante<xref ref-type="bibr" rid="B10">10</xref>.</p>
      <p>Nossos dados n&#227;o demonstraram correla&#231;&#227;o entre o aumento dos di&#226;metros diast&#243;lico e
            sist&#243;lico do ventr&#237;culo esquerdo e a diminui&#231;&#227;o na taxa de sobrevida. Esse dado &#233;
            concordante com Bestetti e cols.<xref ref-type="bibr" rid="B13">13</xref>, Viotti e
               cols.<xref ref-type="bibr" rid="B14">14</xref> e Salles e cols.<xref ref-type="bibr" rid="B15">15</xref>. Evid&#234;ncias de altera&#231;&#245;es na contra&#231;&#227;o segmentar ou global, e um
            aumento no DDFVE tiveram correla&#231;&#227;o significativa com desfecho de mortalidade em uma
            coorte retrospectiva de 424 pacientes avaliados por Rassi e cols.<xref ref-type="bibr" rid="B16">16</xref>. O motivo da n&#227;o confirma&#231;&#227;o desses achados em nossa coorte pode
            ser por ela ser constitu&#237;da de pacientes com disfun&#231;&#227;o sist&#243;lica importante e com
            altera&#231;&#227;o segmentar ou global invariavelmente presente, diferente da coorte
            anteriormente citada. Os aumentos dos volumes diast&#243;lico e sist&#243;lico final do ventr&#237;culo
            esquerdo, assim como a diminui&#231;&#227;o da FE, demonstraram correla&#231;&#227;o com a taxa de
            sobrevida, nesse grupo de pacientes na an&#225;lise univariada, n&#227;o se mantendo, entretanto,
            na an&#225;lise multivariada<xref ref-type="bibr" rid="B13">13</xref>
				<sup>-</sup>
				<xref ref-type="bibr" rid="B16">16</xref>.</p>
      <p>A vari&#225;vel mais comumente relacionada como um fator de predi&#231;&#227;o independente de morte,
            entre os estudos j&#225; realizados, &#233; a FE. Ela avalia a fun&#231;&#227;o sist&#243;lica do ventr&#237;culo
            esquerdo e pode ser obtida por diferentes m&#233;todos na ecocardiografia. Numerosas s&#233;ries
            avaliaram o impacto da queda da FE em rela&#231;&#227;o &#224; sobrevida em pacientes chag&#225;sicos.
               Aquatella<xref ref-type="bibr" rid="B10">10</xref>, em uma meta-an&#225;lise de seis
            s&#233;ries ecocardiogr&#225;ficas envolvendo 3.135 pacientes, mostra com clareza esses
            achados.</p>
      <p>Especificamente, nas s&#233;ries que envolveram pacientes chag&#225;sicos com insufici&#234;ncia
            card&#237;aca grave, o &#250;nico dado ecocardiogr&#225;fico que se mostrou estatisticamente
            significante entre os sobreviventes, pela an&#225;lise multivariada, foi a diminui&#231;&#227;o da FE
            do ventr&#237;culo esquerdo (FE). A primeira delas foi conduzida por Mady e cols.<xref ref-type="bibr" rid="B17">17</xref>, na qual foram avaliados 104 pacientes em classe
            funcional de II a IV, com mortalidade de 50% em um seguimento de 47 meses. A segunda foi
            conduzida por Bestetti e cols.<xref ref-type="bibr" rid="B13">13</xref>, na qual foram
            avaliados 56 pacientes em classes funcionais III e IV, com mortalidade de 28% em um
            seguimento de 24 meses.</p>
      <p>Em outro estudo conduzido na era moderna do tratamento da insufici&#234;ncia card&#237;aca,
            Theodoropoulos e cols.<xref ref-type="bibr" rid="B18">18</xref> avaliaram 127 pacientes
            com diagn&#243;stico de insufici&#234;ncia card&#237;aca sist&#243;lica secund&#225;ria &#224; cardiomiopatia
            chag&#225;sica e observaram que a FE, assim como o uso de betabloqueador, digoxina, n&#237;vel
            s&#233;rico de s&#243;dio e classe funcional IV na admiss&#227;o, foi preditor independente de
            mortalidade, em um seguimento m&#233;dio de 25 meses<xref ref-type="bibr" rid="B18">18</xref>.</p>
      <p>A fun&#231;&#227;o sist&#243;lica do ventr&#237;culo direito n&#227;o foi avaliada em nosso estudo, pois fez
            parte dos par&#226;metros ecocardiogr&#225;ficos do protocolo estabelecido pelo EMRTCC. Por&#233;m &#233;
            importante citar que a presen&#231;a de disfun&#231;&#227;o sist&#243;lica do ventr&#237;culo direito tamb&#233;m &#233; um
            preditor independente de mortalidade na cardiopatia chag&#225;sica, como avaliado por meio do
            &#237;ndice de Tei por Nunes e cols.<xref ref-type="bibr" rid="B19">19</xref> em um estudo
            com 158 pacientes e com seguimento m&#233;dio de 34 meses.</p>
      <p>Em nosso estudo, houve correla&#231;&#227;o significativa entre o di&#226;metro do AE anteroposterior,
            VAE e VAE/m<sup>2</sup> com a taxa de sobrevida desses pacientes. O par&#226;metro
               VAE/m<sup>2</sup> mostrou ser o &#250;nico par&#226;metro ecocardiogr&#225;fico na an&#225;lise
            multivariada, como fator de predi&#231;&#227;o independente de mortalidade cardiovascular nessa
            popula&#231;&#227;o. Quando foi obtido, utilizando-se o ponto de corte &#243;timo de 70,71
               mL/m<sup>2</sup> por meio da an&#225;lise ROC, observou-se &#225;rea sob a curva de 0,827
            (IC95% = 0,708 - 0,913).</p>
      <p>Esses resultados est&#227;o de acordo com os de um recente estudo conduzido por Nunes e
               cols.<xref ref-type="bibr" rid="B20">20</xref>, que avaliaram 192 pacientes
            chag&#225;sicos de maneira prospectiva e com seguimento de 33,8 meses, evidenciando que o
            aumento do VAE/m<sup>2</sup> &#233; um fator de predi&#231;&#227;o independente de morte cardiovascular
            (HR = 1,037 mL/m<sup>2</sup>) e adicionando valor incremental a outros par&#226;metros, como
            FE e medidas derivadas do Doppler, para a avalia&#231;&#227;o da di&#225;stole<xref ref-type="bibr" rid="B20">20</xref>.</p>
      <p>As altera&#231;&#245;es do VAE tamb&#233;m t&#234;m impacto sobre a sobrevida em outras etiologias de
            cardiopatia, como na isqu&#234;mica. M&#248;ller e cols.<xref ref-type="bibr" rid="B21">21</xref>
            acompanharam 314 pacientes, com seguimento m&#233;dio de 15 meses, e demostraram que o
               VAE/m<sup>2</sup> &gt; 32 mL/m<sup>2</sup> foi um importante fator de predi&#231;&#227;o de
            mortalidade, mesmo ap&#243;s ajuste de fatores cl&#237;nicos, fun&#231;&#227;o sist&#243;lica e par&#226;metros
            derivados do Doppler de fun&#231;&#227;o diast&#243;lica<xref ref-type="bibr" rid="B21">21</xref>.</p>
      <p>Quanto os pacientes com disfun&#231;&#227;o sist&#243;lica importante, Rossi e cols.<xref ref-type="bibr" rid="B22">22</xref> realizaram uma meta-an&#225;lise com 1.157 pacientes
            pertencentes a 18 estudos de insufici&#234;ncia card&#237;aca e demostraram que um aumento da &#225;rea
            do AE foi associado com pior progn&#243;stico, independentemente da idade, classe funcional
            da NYHA, FE ou padr&#227;o de enchimento restritivo<xref ref-type="bibr" rid="B22">22</xref>.</p>
      <p>Em nosso grupo de pacientes, n&#227;o foi demonstrada correla&#231;&#227;o com signific&#226;ncia
            estat&#237;stica entre a altera&#231;&#227;o das velocidades das ondas Em e Am e sobrevida. Houve uma
            tend&#234;ncia para a correla&#231;&#227;o da onda Sm com a taxa de sobrevida (p = 0,07). A avalia&#231;&#227;o
            das velocidades teciduais foi realizada na parede septal inferior (segmento basal) e
            muitos pacientes chag&#225;sicos podem apresentar um comprometimento mais intenso nessa
            regi&#227;o, assim como no segmento basal da parede inferior, inferolateral e &#225;pex. Talvez o
            local mais adequado para a essas medi&#231;&#245;es seja outra parede, com menor probabilidade de
            comprometimento segmentar. Outro motivo que pode ter prejudicado nossos par&#226;metros
            teciduais foi o fato de que aproximadamente 30% dos pacientes apresentavam uso de
            marca-passo e 6,6% possu&#237;am ritmo de fibrila&#231;&#227;o atrial. Esses fatores tamb&#233;m dificultam
            a avalia&#231;&#227;o tecidual da di&#225;stole.</p>
      <sec>
        <title>Limita&#231;&#227;o</title>
        <p>Este foi um estudo de an&#225;lise retrospectiva, de dados coletados prospectivamente, que
               implica em limita&#231;&#245;es inerentes a essa qualidade de an&#225;lise.</p>
        <p>N&#227;o houve c&#225;lculo amostral para a an&#225;lise de desfechos, pois a coorte dispon&#237;vel era
               de 60 pacientes. Isso limita poss&#237;veis conclus&#245;es adicionais, devido ao n&#250;mero
               reduzido de desfecho prim&#225;rio (mortalidade).</p>
      </sec>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclus&#227;o</title>
      <p>O aumento do volume indexado do &#225;trio esquerdo mostrou-se como o &#250;nico par&#226;metro
            ecocardiogr&#225;fico que se correlacionou de forma independente com mortalidade
            cardiovascular nesta popula&#231;&#227;o de chag&#225;sicos graves.</p>
    </sec>
  </body>
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    <fn-group>
      <fn fn-type="supported-by">
        <p>
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      </fn>
    </fn-group>
  </back>
  <sub-article article-type="translation" id="TR01" 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">Echocardiographic Parameters and Survival in Chagas Heart
               Disease with Severe Systolic Dysfunction</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Rassi</surname>
            <given-names>Daniela do Carmo</given-names>
          </name>
          <xref ref-type="aff" rid="aff04">1</xref>
          <xref ref-type="corresp" rid="c02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Vieira</surname>
            <given-names>Marcelo Luiz Campos</given-names>
          </name>
          <xref ref-type="aff" rid="aff05">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Arruda</surname>
            <given-names>Ana L&#250;cia Martins</given-names>
          </name>
          <xref ref-type="aff" rid="aff06">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Hotta</surname>
            <given-names>Viviane Tiemi</given-names>
          </name>
          <xref ref-type="aff" rid="aff05">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Furtado</surname>
            <given-names>Rog&#233;rio Gomes</given-names>
          </name>
          <xref ref-type="aff" rid="aff04">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rassi</surname>
            <given-names>Danilo Teixeira</given-names>
          </name>
          <xref ref-type="aff" rid="aff04">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rassi</surname>
            <given-names>Salvador</given-names>
          </name>
          <xref ref-type="aff" rid="aff04">1</xref>
        </contrib>
      </contrib-group>
      <aff id="aff04">
        <label>1</label>
        <institution content-type="orgname">Universidade Federal de Goi&#225;s</institution>
        <institution content-type="orgdiv1">Hospital das Cl&#237;nicas</institution>
        <institution content-type="orgdiv2">Faculdade de Medicina</institution>
        <addr-line>
          <named-content content-type="city">Goi&#226;nia</named-content>
          <named-content content-type="state">GO</named-content>
        </addr-line>
        <country>Brazil</country>
        <institution content-type="original">Faculdade de Medicina e Hospital das Cl&#237;nicas da
               Universidade Federal de Goi&#225;s (UFG), Goi&#226;nia, GO - Brazil</institution>
      </aff>
      <aff id="aff05">
        <label>2</label>
        <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina</institution>
        <institution content-type="orgdiv2">Instituto do Cora&#231;&#227;o</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country>Brazil</country>
        <institution content-type="original">Instituto do Cora&#231;&#227;o da Faculdade de Medicina da
               Universidade de S&#227;o Paulo (USP), S&#227;o Paulo, SP - Brazil</institution>
      </aff>
      <aff id="aff06">
        <label>3</label>
        <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina</institution>
        <institution content-type="orgdiv2">Instituto de Radiologia</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country>Brazil</country>
        <institution content-type="original">Instituto de Radiologia da Faculdade de Medicina da
               Universidade de S&#227;o Paulo (USP), S&#227;o Paulo, SP - Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c02"><bold>Mailing address:</bold> Daniela do Carmo Rassi, Rua 1, n&#250;mero 352, apto 901,
               Edif&#237;cio Reserva dos Buritis, Setor Oeste. Postal Code 74115-040, Goi&#226;nia, GO -
               Brazil. E-mail: <email>dani.rassi@hotmail.com</email>,
                  <email>danirassi@cardiol.br</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research: Rassi DC, Vieira MLC, Arruda ALM, Furtado
                  RG, Rassi DT, Rassi S; Acquisition of data: Rassi DC, Rassi DT, Rassi S; Analysis
                  and interpretation of the data, Critical revision of the manuscript for
                  intellectual content and Writing of the manuscript: Rassi DC, Vieira MLC, Arruda
                  ALM, Hotta VT, Furtado RG, Rassi DT, Rassi S; Statistical analysis: Rassi DC,
                  Vieira MLC, Arruda ALM, Hotta VT, Furtado RG, Rassi S; Obtaining funding: Rassi
                  S.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potential Conflict of Interest</bold>
          </p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Study Association</bold>
          </p>
          <p>This article is part of the thesis of master submitted by Daniela do Carmo Rassi
                  from Faculdade de Medicina da Universidade Federal de Goi&#225;s (UFG).</p>
        </fn>
      </author-notes>
      <abstract xml:lang="en">
        <sec>
          <title>Background:</title>
          <p> Echocardiography provides important information on the cardiac evaluation of
                  patients with heart failure. The identification of echocardiographic parameters in
                  severe Chagas heart disease would help implement treatment and assess prognosis.
               </p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p> To correlate echocardiographic parameters with the endpoint cardiovascular
                  mortality in patients with ejection fraction &lt; 35%. </p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p> Study with retrospective analysis of pre-specified echocardiographic parameters
                  prospectively collected from 60 patients included in the Multicenter Randomized
                  Trial of Cell Therapy in Patients with Heart Diseases (Estudo Multic&#234;ntrico
                  Randomizado de Terapia Celular em Cardiopatias) - Chagas heart disease arm. The
                  following parameters were collected: left ventricular systolic and diastolic
                  diameters and volumes; ejection fraction; left atrial diameter; left atrial
                  volume; indexed left atrial volume; systolic pulmonary artery pressure; integral
                  of the aortic flow velocity; myocardial performance index; rate of increase of
                  left ventricular pressure; isovolumic relaxation time; E, A, Em, Am and Sm wave
                  velocities; E wave deceleration time; E/A and E/Em ratios; and mitral
                  regurgitation. </p>
        </sec>
        <sec>
          <title>Results:</title>
          <p> In the mean 24.18-month follow-up, 27 patients died. The mean ejection fraction
                  was 26.6 &#177; 5.34%. In the multivariate analysis, the parameters ejection fraction
                  (HR = 1.114; p = 0.3704), indexed left atrial volume (HR = 1.033; p &lt; 0.0001)
                  and E/Em ratio (HR = 0.95; p = 0.1261) were excluded. The indexed left atrial
                  volume was an independent predictor in relation to the endpoint, and values &gt;
                  70.71 mL/m<sup>2</sup> were associated with a significant increase in mortality
                  (log rank p &lt; 0.0001). </p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p> The indexed left atrial volume was the only independent predictor of mortality in
                  this population of Chagasic patients with severe systolic dysfunction.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Echocardiography / diagnosis</kwd>
        <kwd>Survivorship (Public Health)</kwd>
        <kwd>Chagas Cardiomyopathy</kwd>
        <kwd>Chagas Disease</kwd>
      </kwd-group>
      <funding-group>
        <award-group>
          <funding-source>FINEP</funding-source>
        </award-group>
      </funding-group>
      <counts>
        <fig-count count="3"/>
        <table-count count="4"/>
        <equation-count count="0"/>
        <ref-count count="22"/>
        <page-count count="8"/>
      </counts>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>One hundred years after been first described, Chagas disease remains a serious health
               and economic problem in most countries in Latin America. Ten million people are
               estimated to be infected worldwide, most of them in Latin America, where the disease
               is endemic. More than 25 million people are at risk for the disease. Chagas disease
               has killed more than 10 thousand people according to an estimate made in 2008<xref ref-type="bibr" rid="B01">1</xref>.</p>
        <p>This parasitic disease is transmitted to man by means of infected feces of
               hematophagous insects in endemic areas and, occasionally, by blood transfusion. Its
               diagnosis is made based on a history suggestive of contact and on two or more
               positive specific serological tests<xref ref-type="bibr" rid="B02">2</xref>
					<sup>,</sup>
					<xref ref-type="bibr" rid="B03">3</xref>.</p>
        <p>Chagas disease has two phases: the acute and chronic phases. The acute phase commonly
               manifests as a self limited febrile syndrome lasting for 2 to 8 weeks, with clinical
               symptoms in less than 1% of patients. In the chronic phase, approximately half of
               these patients remain in the indeterminate form, which has low mortality and a good
               prognosis, whereas the other half progresses to the chronic form, with cardiac and/or
               digestive impairment 10 to 30 years after the initial infection<xref ref-type="bibr" rid="B02">2</xref>
					<sup>,</sup>
					<xref ref-type="bibr" rid="B04">4</xref>
					<sup>,</sup>
					<xref ref-type="bibr" rid="B05">5</xref>.</p>
        <p>The cardiac form is the most common and severe manifestation of Chagas disease in its
               chronic phase. The myocardial abnormalities in the chronic phase are extremely
               variable, ranging from mild forms, such as digitiform apical aneurysms and
               abnormalities of the left ventricular diastolic function only, to significant cardiac
               chamber dilatation, with severe systolic dysfunction<xref ref-type="bibr" rid="B05">5</xref>
					<sup>-</sup>
					<xref ref-type="bibr" rid="B08">8</xref>.</p>
        <p>Echocardiogram is a well-established test in the clinical practice and provides
               parameters by which chagasic patients can be analyzed and stratified. In our study,
               patients with severe systolic dysfunction, who already have a poor prognosis, were
               analyzed. The objective was to identify markers of a poor prognosis that would help
               us start a more aggressive and optimized treatment in an attempt to improve the
               unfavorable outcome of these patients<xref ref-type="bibr" rid="B09">9</xref>
					<sup>,</sup>
					<xref ref-type="bibr" rid="B10">10</xref>.</p>
      </sec>
      <sec sec-type="methods">
        <title>Methods</title>
        <sec>
          <title>Population and study site</title>
          <p>This is a study with retrospective analysis of pre-specified data collected
                  prospectively from patients included in the Multicenter Randomized Trial of Cell
                  Therapy in Heart Diseases (<italic>Estudo Multic&#234;ntrico Randomizado de Terapia
                     Celular em Cardiopatias -</italic> EMRTCC) - Chagas heart disease arm,
                  conducted from February 2006 to February 2009. The EMRTCC was a prospective
                  randomized double blind study, which, in our Institution, had a sample of 60
                  patients with severe systolic dysfunction (ejection fraction - EF &lt; 35%) and
                  NYHA functional classes III and IV. The exclusion criteria were: heart valve
                  diseases, except for functional tricuspid or mitral regurgitation; coronary
                  arteriography showing significant lesion (obstruction of 50% or more in one or
                  more coronary artery); presence of a functioning implantable
                  cardioverter/defibrillator; diseases that could impact the life expectancy or any
                  other comorbidity impacting on the 2-year survival; and echocardiographic images
                  inappropriate for a correct interpretation. The echocardiographic measurements
                  were performed when the patients were randomized. At that moment, optimization of
                  the medical treatment had been achieved, and the patients were hemodynamically
                  stable. The result of the EMRTCC - Chagas heart disease arm, did not show
                  elevation of the EF in the group receiving stem cell implantation, and the
                  population of 60 patients was considered homogeneous, with no influence of the
                  intervention between the two groups<xref ref-type="bibr" rid="B11">11</xref>.</p>
          <p>The primary endpoint of our study was defined as cardiovascular mortality.
                  Cardiovascular mortality was considered as sudden death, when occurring less than
                  1 hour after the change in symptoms, or as death for progressive worsening of
                  heart failure, when resulting from worsening of symptoms or previous hemodynamic
                  deterioration.</p>
          <p>The study was conducted in the Clinics Hospital of the Federal University of Goi&#225;s
                  (HC-UFG). The patients were selected from the heart failure outpatient clinic of
                  the institution. Clinical assessments and follow-up of these patients were carried
                  out in this outpatient clinic. Echocardiography was performed in the imaging
                  service of the institution. The project was approved by the Scientific and Ethics
                  Commission of HC-UFG, and the patients gave written informed consent.</p>
        </sec>
        <sec>
          <title>Echocardiographic assessment</title>
          <p>Echocardiograms were performed in a Xsario ultrasound scanner (Toshiba) available
                  in the department of echocardiography of HC-UFG, with images digitally recorded.
                  Images were obtained according to the criteria established by the American Society
                  of Echocardiography (ASE)<xref ref-type="bibr" rid="B12">12</xref>. All tests were
                  performed by one single highly experienced examiner duly trained to obtain the
                  parameters measured, and in one single scanner of the institution.</p>
          <p>The following parameters of the echocardiographic study were assessed: left
                  ventricular end-diastolic diameter (LVEDD) and LV end-systolic diameter (LVESD);
                  LV end diastolic volume (LVEDV) and LV end-systolic volume (LVESV); EF as
                  estimated by the Simpson's method; left atrial diameter (LA); LA volume (LAV); LAV
                  indexed for body surface (LAV/m<sup>2</sup>); pulmonary artery systolic pressure
                  (PASP); integral of the aortic flow velocity (IFV Ao); derivative of
                  pressure/derivative of time (dP/dT); isovolumic relaxation time (IVRT); myocardial
                  performance index (MPI); E and A wave velocities (by pulsed Doppler); E/A ratio
                  and E wave deceleration time (DCT); myocardial tissue velocity of Em, Am and Sm
                  waves (by tissue Doppler in the basal segment of the inferoseptal wall); and E/Em
                  wave ratio.</p>
        </sec>
        <sec>
          <title>Statistical analysis</title>
          <p>The survival curves were calculated using the Kapplan-Meier product-limit method,
                  and compared using the log-rank test. Survival probabilities were estimated with a
                  95% confidence interval (CI). Quantitative variables were dichotomized using the
                  optimal cut-off point obtained from the ROC (Receiver Operating Characteristic)
                  analyses. Non-adjusted and adjusted hazard ratios (HR) with 95% CI were estimated
                  in the Cox univariate and multivariate regression analyses, respectively. The
                  multiple regression model used the proportion of number of events per variable of
                  9:1, with confirmed balanced estimates. Normality of variables was assessed using
                  the Kolmogorov-Smirnov test, and were represented as mean &#177; standard deviation or
                  median and 95% CI, depending on a normal or non-normal distribution, respectively.
                  All probabilities of significance (p values) presented are two-sided and values
                  &lt; 0.05 were considered statistically significant. P values between 0.05 and
                  0.10 were interpreted as marginally significant. The statistical analysis of data
                  was carried out using the Stata 11 (Stata Corp, College Station, TX) and SAS 9.2
                  (Statistical Analysis System, Cary, NC) software programs.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Results</title>
        <p>Clinical and echocardiographic characteristics of the study group are shown in <xref ref-type="table" rid="t05">Tables 1</xref> and <xref ref-type="table" rid="t06">2</xref>, respectively.</p>
        <table-wrap id="t05">
          <label>Table 1</label>
          <caption>
            <title>Clinical characteristics of the group</title>
          </caption>
          <table rules="rows" frame="hsides">
            <thead>
              <tr>
                <td>
                  <bold>Characteristic</bold>
                </td>
                <td align="center">
                  <bold>Mean &#177; SD</bold>
                </td>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>Age (years)</td>
                <td align="center">50.9 &#177; 9.3</td>
              </tr>
              <tr>
                <td>Gender (%)</td>
                <td align="center">n = 60</td>
              </tr>
              <tr>
                <td>Male</td>
                <td align="center">70</td>
              </tr>
              <tr>
                <td>Drug therapy (%)</td>
                <td align="center">n = 60</td>
              </tr>
              <tr>
                <td>Diuretics</td>
                <td align="center">88.3</td>
              </tr>
              <tr>
                <td>ACEI</td>
                <td align="center">60</td>
              </tr>
              <tr>
                <td>ARB</td>
                <td align="center">21</td>
              </tr>
              <tr>
                <td>Betablocker</td>
                <td align="center">60</td>
              </tr>
              <tr>
                <td>Spironolactone</td>
                <td align="center">85</td>
              </tr>
              <tr>
                <td>Digoxin</td>
                <td align="center">61</td>
              </tr>
              <tr>
                <td>Amiodarone</td>
                <td align="center">58.33</td>
              </tr>
              <tr>
                <td>Rhythm in atrial fibrilation (%)</td>
                <td align="center">6.6</td>
              </tr>
              <tr>
                <td>Pacemaker (%)</td>
                <td align="center">30</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn>
              <p>SD: standard deviation; ACEI: angiotensin converting enzyme inhibitor; ARB:
                        angiotensin II receptor blocker.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <table-wrap id="t06">
          <label>Table 2</label>
          <caption>
            <title>Echocardiographic characteristics of the group</title>
          </caption>
          <table rules="rows" frame="hsides">
            <thead>
              <tr>
                <td rowspan="2">
                  <bold>Variable</bold>
                </td>
                <td rowspan="2" align="center">
                  <bold>p (KS)</bold>
                </td>
                <td align="center"/>
                <td align="center">
                  <bold>Parameters</bold>
                </td>
                <td align="center"/>
              </tr>
              <tr>
                <td align="center">
                  <bold>Mean &#177; SD</bold>
                </td>
                <td align="center">
                  <bold>Median</bold>
                </td>
                <td align="center">
                  <bold>95% CI</bold>
                </td>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>EF (%)</td>
                <td align="center">0.617</td>
                <td align="center">26.7 &#177; 5.3</td>
                <td align="center">27.4</td>
                <td align="center">25.3 - 28.1</td>
              </tr>
              <tr>
                <td>LVEDD (mm)</td>
                <td align="center">0.667</td>
                <td align="center">78.9 &#177; 8.7</td>
                <td align="center">78.6</td>
                <td align="center">76.7 - 81.2</td>
              </tr>
              <tr>
                <td>LVESD (mm)</td>
                <td align="center">0.485</td>
                <td align="center">67.4 &#177; 8.0</td>
                <td align="center">67.3</td>
                <td align="center">65.3 - 69.5</td>
              </tr>
              <tr>
                <td>LVEDV (mL)</td>
                <td align="center">0.724</td>
                <td align="center">271.3 &#177; 94.5</td>
                <td align="center">265.6</td>
                <td align="center">246.9 - 295.7</td>
              </tr>
              <tr>
                <td>LVESV (mL)</td>
                <td align="center">0.855</td>
                <td align="center">189.3 &#177; 73.0</td>
                <td align="center">186.8</td>
                <td align="center">170.5 - 208.2</td>
              </tr>
              <tr>
                <td>LA (mm)</td>
                <td align="center">0.833</td>
                <td align="center">48.3 &#177; 8.5</td>
                <td align="center">48.0</td>
                <td align="center">46.1 - 50.5</td>
              </tr>
              <tr>
                <td>LAV (mL)</td>
                <td align="center">0.375</td>
                <td align="center">104.9 &#177; 42.3</td>
                <td align="center">98.7</td>
                <td align="center">93.9 - 115.8</td>
              </tr>
              <tr>
                <td>LAV/m<sup>2</sup> (ml/m<sup>2</sup>)</td>
                <td align="center">0.330</td>
                <td align="center">62.9 &#177; 24.4</td>
                <td align="center">58.8</td>
                <td align="center">56.6 - 69.2</td>
              </tr>
              <tr>
                <td>PASP (mmHg)</td>
                <td align="center">0.022<xref ref-type="table-fn" rid="t06-fn01">*</xref>
								</td>
                <td align="center">38.1 &#177; 13.4</td>
                <td align="center">33.6</td>
                <td align="center">34.3 - 41.9</td>
              </tr>
              <tr>
                <td>IFV Ao (cm)</td>
                <td align="center">0.002<xref ref-type="table-fn" rid="t06-fn01">*</xref>
								</td>
                <td align="center">13.2 &#177; 8.7</td>
                <td align="center">12.0</td>
                <td align="center">10.9 - 15.5</td>
              </tr>
              <tr>
                <td>DCT (ms)</td>
                <td align="center">0.122</td>
                <td align="center">188.0 &#177; 92.3</td>
                <td align="center">160.0</td>
                <td align="center">164.2 - 211.8</td>
              </tr>
              <tr>
                <td>MPI</td>
                <td align="center">0.026<xref ref-type="table-fn" rid="t06-fn01">*</xref>
								</td>
                <td align="center">0.89 &#177; 0.40</td>
                <td align="center">0.82</td>
                <td align="center">0.79 - 0.99</td>
              </tr>
              <tr>
                <td>dP/dT</td>
                <td align="center">0.286</td>
                <td align="center">489.6 &#177; 162.3</td>
                <td align="center">444.0</td>
                <td align="center">447.7 - 531.5</td>
              </tr>
              <tr>
                <td>IVRT (ms)</td>
                <td align="center">0.005<xref ref-type="table-fn" rid="t06-fn01">*</xref>
								</td>
                <td align="center">116.9 &#177; 72.1</td>
                <td align="center">100.0</td>
                <td align="center">98.3 - 135.6</td>
              </tr>
              <tr>
                <td>A (cm/s)</td>
                <td align="center">0.426</td>
                <td align="center">46.8 &#177; 23.3</td>
                <td align="center">41.3</td>
                <td align="center">40.5 - 53.1</td>
              </tr>
              <tr>
                <td>E (cm/s)</td>
                <td align="center">0.522</td>
                <td align="center">63.9 &#177; 25.0</td>
                <td align="center">61.4</td>
                <td align="center">57.5 - 70.4</td>
              </tr>
              <tr>
                <td>Am (cm/s)</td>
                <td align="center">0.853</td>
                <td align="center">4.8 &#177; 2.1</td>
                <td align="center">4.5</td>
                <td align="center">4.3 - 5.4</td>
              </tr>
              <tr>
                <td>Em (cm/s)</td>
                <td align="center">0.395</td>
                <td align="center">4.8 &#177; 1.7</td>
                <td align="center">4.5</td>
                <td align="center">4.4 - 5.3</td>
              </tr>
              <tr>
                <td>Sm (cm/s)</td>
                <td align="center">0.774</td>
                <td align="center">4.6 &#177; 1.2</td>
                <td align="center">4.7</td>
                <td align="center">4.3 - 4.9</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="t06-fn01">
              <label>*</label>
              <p> Signifcant: variables statistically significant. HR: hazard ratio; 95% CI:
                        95% confidence interval; EF: ejection fraction; LVEDD: left ventricular
                        end-diastolic diameter; LVESD: left ventricular end-systolic diameter;
                        LVEDV: left ventricular end-diastolic volume; LVESV: left ventricular
                        end-systolic volume; LA: left atrial anteroposterior measurement; LAV: left
                        atrial volume; LAV/m<sup>2</sup>: left atrial volume indexed for body
                        surface; PASP: pulmonary artery systolic pressure; IFV Ao: integral of the
                        aortic flow velocity; DCT: E wave deceleration time; MPI: myocardial
                        performance index; dP/dT: derivative of the pressure/derivative of time;
                        IVRT: isovolumic relaxation time; A: transmitral flow velocity of late
                        ventricular filling; E: transmitral flow velocity of early ventricular
                        filling; E/A: E and A wave ratio; Em and Am: diastolic tissue velocities;
                        Sm: systolic tissue velocity; E/Em: E and Em wave ratio; MR 1 vs. 2: mild
                        versus moderate mitral regurgitation.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Cardiovascular deaths occurred in 27 (45%) of the 60 patients in a mean follow-up of
               24 months (<xref ref-type="fig" rid="f04">Figure 1</xref>). All remained with
               optimized drug therapy and did not receive resynchronization therapy or implantable
               cardio-defibrillator during the follow-up.</p>
        <fig id="f04" fig-type="other">
          <label>Figure 1</label>
          <caption>
            <title>Kapplan-Meier curve with analysis of overall survival in the study
                     population</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-102-03-0245-40003-gf01-en.jpg"/></fig>
        <sec>
          <title>Analysis of the echocardiographic parameters</title>
          <p>The association between the echocardiographic parameters and the endpoint was
                  initially assessed by univariate analysis (<xref ref-type="table" rid="t07">Table
                     3</xref>).</p>
          <table-wrap id="t07">
            <label>Table 3</label>
            <caption>
              <title>Univariate analysis of predictors of cardiovascular events</title>
            </caption>
            <table rules="rows" frame="hsides">
              <thead>
                <tr>
                  <td align="center">
                    <bold>Parameter</bold>
                  </td>
                  <td align="center">
                    <bold>n</bold>
                  </td>
                  <td align="center">
                    <bold>Events</bold>
                  </td>
                  <td align="center">
                    <bold>HR</bold>
                  </td>
                  <td align="center">
                    <bold>Lowest 95%CI</bold>
                  </td>
                  <td align="center">
                    <bold>Highest 95%CI</bold>
                  </td>
                  <td align="center">
                    <bold>p value</bold>
                  </td>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>EF</td>
                  <td align="center">60</td>
                  <td align="center">27</td>
                  <td align="center">0.932</td>
                  <td align="center">0.873</td>
                  <td align="center">0.994</td>
                  <td align="center">0.031<xref ref-type="table-fn" rid="t07-fn01">*</xref>
									</td>
                </tr>
                <tr>
                  <td>LVEDD</td>
                  <td align="center">60</td>
                  <td align="center">27</td>
                  <td align="center">1.036</td>
                  <td align="center">0.988</td>
                  <td align="center">1.087</td>
                  <td align="center">0.1464</td>
                </tr>
                <tr>
                  <td>LVESD</td>
                  <td align="center">60</td>
                  <td align="center">27</td>
                  <td align="center">2.573</td>
                  <td align="center">0.972</td>
                  <td align="center">6.81</td>
                  <td align="center">0.057</td>
                </tr>
                <tr>
                  <td>LVEDV</td>
                  <td align="center">60</td>
                  <td align="center">27</td>
                  <td align="center">1.005</td>
                  <td align="center">1.001</td>
                  <td align="center">1.009</td>
                  <td align="center">0.0275<xref ref-type="table-fn" rid="t07-fn01">*</xref>
									</td>
                </tr>
                <tr>
                  <td>LVESV</td>
                  <td align="center">60</td>
                  <td align="center">27</td>
                  <td align="center">1.005</td>
                  <td align="center">1</td>
                  <td align="center">1.01</td>
                  <td align="center">0.0403<xref ref-type="table-fn" rid="t07-fn01">*</xref>
									</td>
                </tr>
                <tr>
                  <td>LA</td>
                  <td align="center">60</td>
                  <td align="center">27</td>
                  <td align="center">1.064</td>
                  <td align="center">1.021</td>
                  <td align="center">1.109</td>
                  <td align="center">0.0031<xref ref-type="table-fn" rid="t07-fn01">*</xref>
									</td>
                </tr>
                <tr>
                  <td>LAV</td>
                  <td align="center">60</td>
                  <td align="center">27</td>
                  <td align="center">1.015</td>
                  <td align="center">1.008</td>
                  <td align="center">1.021</td>
                  <td align="center">&lt; 0.0001<xref ref-type="table-fn" rid="t07-fn01">*</xref>
									</td>
                </tr>
                <tr>
                  <td>LAV/m<sup>2</sup>
									</td>
                  <td align="center">60</td>
                  <td align="center">24</td>
                  <td align="center">1.036</td>
                  <td align="center">1.021</td>
                  <td align="center">1.051</td>
                  <td align="center">&lt; 0.0001<xref ref-type="table-fn" rid="t07-fn01">*</xref>
									</td>
                </tr>
                <tr>
                  <td>PASP</td>
                  <td align="center">50</td>
                  <td align="center">27</td>
                  <td align="center">1.039</td>
                  <td align="center">1.012</td>
                  <td align="center">1.067</td>
                  <td align="center">0.0039<xref ref-type="table-fn" rid="t07-fn01">*</xref>
									</td>
                </tr>
                <tr>
                  <td>IFV Ao</td>
                  <td align="center">59</td>
                  <td align="center">26</td>
                  <td align="center">0.947</td>
                  <td align="center">0.852</td>
                  <td align="center">1.053</td>
                  <td align="center">0.3151</td>
                </tr>
                <tr>
                  <td>DCT</td>
                  <td align="center">60</td>
                  <td align="center">27</td>
                  <td align="center">0.993</td>
                  <td align="center">0.987</td>
                  <td align="center">0.998</td>
                  <td align="center">0.0093<xref ref-type="table-fn" rid="t07-fn01">*</xref>
									</td>
                </tr>
                <tr>
                  <td>MPI</td>
                  <td align="center">60</td>
                  <td align="center">27</td>
                  <td align="center">2.423</td>
                  <td align="center">1.032</td>
                  <td align="center">5.689</td>
                  <td align="center">0.0421<xref ref-type="table-fn" rid="t07-fn01">*</xref>
									</td>
                </tr>
                <tr>
                  <td>dP/dT</td>
                  <td align="center">60</td>
                  <td align="center">27</td>
                  <td align="center">1</td>
                  <td align="center">0.998</td>
                  <td align="center">1.003</td>
                  <td align="center">0.7342</td>
                </tr>
                <tr>
                  <td>IVRT</td>
                  <td align="center">60</td>
                  <td align="center">27</td>
                  <td align="center">0.997</td>
                  <td align="center">0.99</td>
                  <td align="center">1.004</td>
                  <td align="center">0.3499</td>
                </tr>
                <tr>
                  <td>A</td>
                  <td align="center">56</td>
                  <td align="center">23</td>
                  <td align="center">0.976</td>
                  <td align="center">0.956</td>
                  <td align="center">0.996</td>
                  <td align="center">0.0212<xref ref-type="table-fn" rid="t07-fn01">*</xref>
									</td>
                </tr>
                <tr>
                  <td>E</td>
                  <td align="center">60</td>
                  <td align="center">27</td>
                  <td align="center">1.029</td>
                  <td align="center">1.013</td>
                  <td align="center">1.046</td>
                  <td align="center">0.0004<xref ref-type="table-fn" rid="t07-fn01">*</xref>
									</td>
                </tr>
                <tr>
                  <td>E/A</td>
                  <td align="center">56</td>
                  <td align="center">23</td>
                  <td align="center">1.589</td>
                  <td align="center">1.205</td>
                  <td align="center">2.096</td>
                  <td align="center">0.001<xref ref-type="table-fn" rid="t07-fn01">*</xref>
									</td>
                </tr>
                <tr>
                  <td>Am</td>
                  <td align="center">56</td>
                  <td align="center">23</td>
                  <td align="center">0.847</td>
                  <td align="center">0.687</td>
                  <td align="center">1.044</td>
                  <td align="center">0.1192</td>
                </tr>
                <tr>
                  <td>Em</td>
                  <td align="center">60</td>
                  <td align="center">27</td>
                  <td align="center">1.003</td>
                  <td align="center">0.805</td>
                  <td align="center">1.249</td>
                  <td align="center">0.9815</td>
                </tr>
                <tr>
                  <td>Sm</td>
                  <td align="center">60</td>
                  <td align="center">27</td>
                  <td align="center">0.726</td>
                  <td align="center">0.514</td>
                  <td align="center">1.026</td>
                  <td align="center">0.07<xref ref-type="table-fn" rid="t07-fn01">*</xref>
									</td>
                </tr>
                <tr>
                  <td>E/ EM</td>
                  <td align="center">59</td>
                  <td align="center">27</td>
                  <td align="center">1.083</td>
                  <td align="center">1.019</td>
                  <td align="center">1.151</td>
                  <td align="center">0.0104<xref ref-type="table-fn" rid="t07-fn01">*</xref>
									</td>
                </tr>
                <tr>
                  <td>MR 1 vs. 2</td>
                  <td align="center">60</td>
                  <td align="center">27</td>
                  <td align="center">0.325</td>
                  <td align="center">0.146</td>
                  <td align="center">0.728</td>
                  <td align="center">0.0063<xref ref-type="table-fn" rid="t07-fn01">*</xref>
									</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="t07-fn01">
                <label>*</label>
                <p> Signifcant: variables statistically significant. HR: hazard ratio; 95%
                           CI: 95% confidence interval; EF: ejection fraction; LVEDD: left
                           ventricular end-diastolic diameter; LVESD: left ventricular end-systolic
                           diameter; LVEDV: left ventricular end-diastolic volume; LVESV: left
                           ventricular end-systolic volume; LA: left atrial anteroposterior
                           measurement; LAV left atrial volume; LAV/m': left atrial volume indexed
                           for body surface; PASP: pulmonary artery systolic pressure; IFV Ao:
                           integral of the aortic flow velocity; DCT E wave deceleration time; MPI:
                           myocardial performance index; dP/dT: derivative of the
                           pressure/derivative of time; IVRT: isovolumic relaxation time; A:
                           transmitral flow velocity of late ventricular filling; E: transmitral
                           flow velocity of early ventricular filling; E/A: E and A wave ratio; Em
                           and Am: diastolic tissue velocities; Sm: systolic tissue velocity; E/Em:
                           E and Em wave ratio; MR 1 vs. 2: mild versus moderate mitral
                           regurgitation.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>Based on the clinical relevance and aiming to include anatomical and functional
                  data, three echocardiographic parameters were selected for the multivariate
                  analysis (<xref ref-type="table" rid="t08">Table 4</xref>).</p>
          <table-wrap id="t08">
            <label>Table 4</label>
            <caption>
              <title>Multivariate analysis of predictors of cardiovascular events</title>
            </caption>
            <table rules="rows" frame="hsides">
              <thead>
                <tr>
                  <td>
                    <bold>Parameter</bold>
                  </td>
                  <td align="center">
                    <bold>Regression coefficient (beta)</bold>
                  </td>
                  <td align="center">
                    <bold>HR</bold>
                  </td>
                  <td align="center">
                    <bold>Lowest 95%CI</bold>
                  </td>
                  <td align="center">
                    <bold>Highest 95%CI</bold>
                  </td>
                  <td align="center">
                    <bold>p value</bold>
                  </td>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>EF </td>
                  <td align="center">-0.0508945</td>
                  <td align="center">0.95</td>
                  <td align="center">0.89</td>
                  <td align="center">1.014</td>
                  <td align="center">0.1261</td>
                </tr>
                <tr>
                  <td>LAV/m2 </td>
                  <td align="center">0.0321653</td>
                  <td align="center">1.033</td>
                  <td align="center">1.017</td>
                  <td align="center">1.049</td>
                  <td align="center">&lt; 0.0001<xref ref-type="table-fn" rid="t08-fn01">*</xref>
									</td>
                </tr>
                <tr>
                  <td>E/Em </td>
                  <td align="center">0.0337537</td>
                  <td align="center">1.034</td>
                  <td align="center">0.961</td>
                  <td align="center">1.114</td>
                  <td align="center">0.3704</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="t08-fn01">
                <label>*</label>
                <p> Signifcant: variables statistically significant. HR: risk ratio; 95% CI:
                           95% confidence interval; EF: ejection fraction; LAV/m<sup>2</sup>: left
                           atrial volume indexed for body surface; E/Em: E (transmitral flow
                           velocity of filling) and Em (diastolic tissue velocity) wave ratio.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>Among the parameters assessed, only LAV/m<sup>2</sup> proved to be an independent
                  predictor in relation to the endpoint.</p>
          <p>When an LAV/m<sup>2</sup> value of 70.71 mL/m<sup>2</sup> was obtained, a larger
                  distance between the study population was observed in relation to the endpoint
                  mortality (<xref ref-type="fig" rid="f05">Figure 2</xref>), with an area under the
                  curve of 0.827 (95% CI = 0.708 - 0.913) (<xref ref-type="fig" rid="f06">Figure
                     3</xref>).</p>
          <fig id="f05" fig-type="other">
            <label>Figure 2</label>
            <caption>
              <title>Relationship between survival and Indexed Left Atrial Volume (LAV
                           /m<sup>2</sup>)</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-102-03-0245-40003-gf02-en.jpg"/></fig>
          <fig id="f06" fig-type="other">
            <label>Figure 3</label>
            <caption>
              <title>ROC curve of the indexed left atrial volume</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-102-03-0245-40003-gf03-en.jpg"/></fig>
        </sec>
      </sec>
      <sec sec-type="discussion">
        <title>Discussion</title>
        <p>Most of the echocardiographic studies involving patients with chronic chagasic
               cardiomyopathy sought to correlate echocardiographic parameters with survival, using
               proportional hazards models (Cox models). The populations assessed in these studies
               had varying expressions of the disease ranging from no cardiac impairment to severe
               disease with significant symptoms. In our study, exclusively patients presenting with
               severe structural cardiac involvement and significant systolic dysfunction were
                  selected<xref ref-type="bibr" rid="B10">10</xref>.</p>
        <p>Our results did not demonstrate a correlation between increased left ventricular
               diastolic and systolic diameters and decreased survival rates. This is consistent
               with Bestetti et al<xref ref-type="bibr" rid="B13">13</xref>, Viotti et al<xref ref-type="bibr" rid="B14">14</xref>, and Salles et al<xref ref-type="bibr" rid="B15">15</xref> findings. Evidences of segmental or global wall motion
               abnormalities and increased LVEDD significantly correlated with the endpoint
               mortality in a retrospective cohort of 424 patients evaluated by Rassi et al<xref ref-type="bibr" rid="B16">16</xref>. We may have not confirmed these findings in
               our cohort because it was comprised of patients with severe systolic dysfunction and
               segmental or global wall motion abnormalities invariably present, unlike Rassi's
                  cohort<xref ref-type="bibr" rid="B16">16</xref>. Increases in LVEDV and LVESV, as
               well as decrease in EF, correlated with the survival rate in the univariate analysis
               of this group of patients; however this was not confirmed in the multivariate
                  analysis<xref ref-type="bibr" rid="B13">13</xref>
					<sup>-</sup>
					<xref ref-type="bibr" rid="B16">16</xref>.</p>
        <p>The variable most commonly described as an independent predictor of death among the
               studies previously conducted is EF. This variable assesses the left ventricular
               systolic function and may be obtained by echocardiography using different methods.
               Several studies have evaluated the impact of the decrease in EF in relation to the
               survival of chagasic patients. In a meta-analysis of six echocardiographic series
               involving 3,135 patients, Aquatella<xref ref-type="bibr" rid="B10">10</xref> clearly
               demonstrated these findings.</p>
        <p>Specifically, in the series involving chagasic patients with severe heart failure,
               the only echocardiographic finding that proved to be statistically significant among
               survivors, in the multivariate analysis, was the decrease in left ventricular EF
               (LVEF). The first of them was conducted by Mady et al<xref ref-type="bibr" rid="B17">17</xref>, in which 104 patients in functional class from II to IV were assessed,
               with a 50% mortality in a 47-month follow-up. The second was conducted by Bestetti et
                  al<xref ref-type="bibr" rid="B13">13</xref>, in which 56 patients in functional
               classes III and IV were evaluated, with a 28% mortality in a 24-month follow-up. </p>
        <p>In another study conducted in the modern era of the treatment for heart disease,
               Theodoropoulos et al<xref ref-type="bibr" rid="B18">18</xref> evaluated 127 patients
               diagnosed with systolic heart failure secondary to chagasic cardiomyopathy and
               observed that LVEF, as well as the use of betablockers, digoxin, serum sodium level,
               and functional class IV on admission were independent predictors of mortality in a
               mean 25-month follow-up<xref ref-type="bibr" rid="B18">18</xref>.</p>
        <p>The right ventricular systolic function was not assessed in our study, because it was
               part of the echocardiographic parameters of the protocol established by EMRTCC.
               However, we should point out that the presence of right ventricular systolic
               dysfunction is also an independent predictor of mortality in chagasic cardiomyopathy,
               as demonstrated by Nunes et al<xref ref-type="bibr" rid="B19">19</xref> in a study of
               158 patients and a mean 34-month follow-up, in which this parameter was assessed
               using the Tei index.</p>
        <p>In our study, there was a significant correlation of the anteroposterior LA diameter,
               LAV, and LAV/m<sup>2</sup> with the survival rate of these patients.
                  LAV/m<sup>2</sup> was the only echocardiographic parameter in the multivariate
               analysis that proved to be an independent predictor of cardiovascular mortality in
               this population. When obtained, using an optimal cut-off point of 70.71
                  mL/m<sup>2</sup> by means of the ROC analysis, we observed an area under the curve
               of 0.827 (95% CI = 0.708 - 0.913).</p>
        <p>These results corroborate those of a recent study conducted by Nunes et al<xref ref-type="bibr" rid="B20">20</xref>, who evaluated 192 chagasic patients
               retrospectively in a follow-up of 33.8 months. The authors showed that the increase
               in LAV/m<sup>2</sup> is an independent predictor of cardiovascular mortality (HR =
               1.037 mL/m<sup>2</sup>) and increments the value of other parameters such as EF and
               Doppler-derived measurements in the assessment of diastole<xref ref-type="bibr" rid="B20">20</xref>.</p>
        <p>LAV abnormalities also have an impact on the survival in heart diseases of other
               causes, such as ischemic heart disease. M&#248;ller et al<xref ref-type="bibr" rid="B21">21</xref> followed up 314 patients for a mean of 15 months and showed that LAV
                  mL/m<sup>2</sup> &gt; 32 mL/m<sup>2</sup> was an important predictor of mortality,
               even after adjustment for clinical factors, systolic function, and Doppler-derived
               parameters of diastolic function<xref ref-type="bibr" rid="B21">21</xref>.</p>
        <p>As for patients with severe systolic dysfunction, Rossi et al<xref ref-type="bibr" rid="B22">22</xref> conducted a meta-analysis with 1157 patients from 18 studies
               on heart failure and demonstrated than increased LA area was associated with a worse
               prognosis, regardless of age, NYHA functional class, EF, or restrictive filling
                  pattern<xref ref-type="bibr" rid="B22">22</xref>.</p>
        <p>In our group of patients, no statistically significant correlation was demonstrated
               between Em and Am wave velocity abnormalities and survival. There was a tendency for
               a correlation between Sm wave and survival rate (p = 0.07). Tissue velocities were
               evaluated in the inferoseptal wall (basal segment); many chagasic patients may show
               greater impairment in this region, as well as in the basal segment of the inferior
               and inferolateral wall and apex. Perhaps the most appropriate site for these
               measurements is another wall, where the probability of segmental impairment is lower.
               Another factor that may have compromised our tissue parameters was that approximately
               30% of patients used pacemakers and 6.6% had rhythm in atrial fibrillation. These
               factors also compromise tissue assessment during diastole.</p>
        <sec>
          <title>Limitation</title>
          <p>This was a study of retrospective analysis of data prospectively collected, and
                  this implies in limitations inherent to this type of analysis.</p>
          <p>There was no sample calculation for the analysis of endpoints, because the cohort
                  available was of 60 patients. This limits possible additional conclusions, because
                  of the small number of primary endpoint (mortality).</p>
        </sec>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclusion</title>
        <p>Increased indexed left atrial volume proved to be the only echocardiographic
               parameter to independently correlate with cardiovascular mortality in this population
               of severely ill chagasic patients.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="financial-disclosure">
          <p>
            <bold>Sources of Funding</bold>
          </p>
          <p>This study was funded by FINEP.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
