<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.1 20151215//EN" "http://jats.nlm.nih.gov/publishing/1.1/JATS-journalpublishing1.dtd">
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.1" specific-use="sps-1.9" xml:lang="pt">
  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id specific-use="scielo-v3" pub-id-type="publisher-id">JBrw5c5hcrTrTMyHRLDgFwp</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2020000800071</article-id>
      <article-id pub-id-type="publisher-id">abc.20190281</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20190281</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo Original</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Avalia&#231;&#227;o da Din&#226;mica do Acoplamento da Condu&#231;&#227;o Atrioventricular &#224; Varia&#231;&#227;o dos Intervalos RR em Atletas e Indiv&#237;duos Sedent&#225;rios</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-4782-822X</contrib-id>
          <name>
            <surname>Benchimol-Barbosa</surname>
            <given-names>Paulo Roberto</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nasario</surname>
            <given-names>Olivass&#233;</given-names>
            <suffix>Junior</suffix>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nadal</surname>
            <given-names>Jurandir</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">Hospital Universit&#225;rio Pedro Ernesto</institution>
        <addr-line>
          <named-content content-type="city">Rio de Janeiro</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Hospital Universit&#225;rio Pedro Ernesto, Coordena&#231;&#227;o Cl&#237;nica, Rio de Janeiro, RJ &#8211; Brasil</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgname">Universidade Federal do Rio de Janeiro</institution>
        <institution content-type="orgdiv1">Instituto Alberto Luiz Coimbra de P&#243;s-Gradua&#231;&#227;o e Pesquisa de Engenharia</institution>
        <addr-line>
          <named-content content-type="city">Rio de Janeiro</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Universidade Federal do Rio de Janeiro, Instituto Alberto Luiz Coimbra de P&#243;s-Gradua&#231;&#227;o e Pesquisa de Engenharia, Rio de Janeiro, RJ &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c01"> Correspond&#234;ncia: Paulo Roberto Benchimol-Barbosa &#8226; Hospital Universit&#225;rio Pedro Ernesto &#8211; Boulevard Vinte e Oito de setembro, 77, Gabinete da Dire&#231;&#227;o Geral, T&#233;rreo. CEP 20551-030, Rio de Janeiro, RJ &#8211; Brasil E-mail: <email>ecgar@yahoo.com</email> , <email>benchimol@globo.com</email> </corresp>
        <fn fn-type="con">
          <p>Contribui&#231;&#227;o dos autores</p>
          <p>Concep&#231;&#227;o e desenho da pesquisa: Benchimol-Barbosa PR, Nasario-Junior O, Nadal J. Obten&#231;&#227;o de dados: Benchimol-Barbosa PR. An&#225;lise e interpreta&#231;&#227;o dos dados: Benchimol-Barbosa PR, Nasario-Junior O, Nadal J. An&#225;lise estat&#237;stica: Benchimol-Barbosa PR, Nadal J. Obten&#231;&#227;o de financiamento: Nadal J. Reda&#231;&#227;o do manuscrito: Benchimol-Barbosa PR, Nasario-Junior O, Nadal J. Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Benchimol-Barbosa PR, Nasario-Junior O, Nadal J.</p>
        </fn>
        <fn fn-type="conflict">
          <p>Potencial Conflito de Interesse</p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>08</day>
        <month>05</month>
        <year>2020</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>07</month>
        <year>2020</year>
      </pub-date>
      <volume>115</volume>
      <issue>1</issue>
      <fpage>71</fpage>
      <lpage>77</lpage>
      <history>
        <date date-type="received">
          <day>30</day>
          <month>04</month>
          <year>2019</year>
        </date>
        <date date-type="rev-recd">
          <day>02</day>
          <month>07</month>
          <year>2019</year>
        </date>
        <date date-type="accepted">
          <day>01</day>
          <month>08</month>
          <year>2019</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <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>
        <title>Resumo</title>
        <sec>
          <title>Fundamento</title>
          <p> O tempo de condu&#231;&#227;o atrioventricular (TCAV) &#233; influenciado pelo est&#237;mulo auton&#244;mico e sujeito a remodela&#231;&#227;o fisiol&#243;gica.</p>
        </sec>
        <sec>
          <title>Objetivo</title>
          <p> Avaliar a variabilidade da TCAV batimento-a-batimento e o intervalo RR em atletas e indiv&#237;duos sedent&#225;rios saud&#225;veis.</p>
        </sec>
        <sec>
          <title>M&#233;todos</title>
          <p> Vinte adultos, incluindo 10 indiv&#237;duos sedent&#225;rios saud&#225;veis (controles) e 10 corredores de elite de longa dist&#226;ncia (atletas), com idade, peso e altura ajustados foram submetidos &#224; avalia&#231;&#227;o do equivalente metab&#243;lico m&#225;ximo (MET) e registro de ECG em repouso supino de 15 minutos sete dias depois. O intervalo entre os picos da onda P e da onda R definiu o TCAV. Foram calculadas a m&#233;dia (M) e o desvio padr&#227;o (DP) de intervalos RR consecutivos (RR) e TCAV acoplados, bem como as linhas de regress&#227;o de RR vs. TCAV (RR-TCAV). A condu&#231;&#227;o AV concordante foi definida como o <italic>slope</italic> RR-AVCT positivo e, caso contr&#225;rio, discordante. Um modelo de regress&#227;o linear multivariada foi desenvolvido para explicar o MET com base nos par&#226;metros de variabilidade do TCAV e intervalo RR. N&#237;vel de signific&#226;ncia: 5%.</p>
        </sec>
        <sec>
          <title>Resultados</title>
          <p> Nos atletas, os valores de M-RR e DP-RR foram maiores que nos controles, enquanto M-TCAV e DP-TCAV n&#227;o foram. Os <italic>slopes</italic> RR-TCAV foram, respectivamente, 0,038 &#177; 0,022 e 0,0034 &#177; 0,017 (p &lt; 0,05). Utilizando um valor de corte de 0,0044 (AUC 0,92 &#177; 0,07; p &lt; 0,001), o <italic>slope</italic> RR-TCAV mostrou 100% de especificidade e 80% de sensibilidade. Em um modelo multivariado, o <italic>slope</italic> DP-RR e RR-TCAV foram vari&#225;veis explicativas independentes do MET (raz&#227;o F: 17,2; p &lt; 0,001), apresentando especificidade de 100% e sensibilidade de 90% (AUC: 0,99 &#177; 0,02; p &lt; 0,001).</p>
        </sec>
        <sec>
          <title>Conclus&#227;o</title>
          <p> Em corredores de elite, o acoplamento din&#226;mico de TCAV para intervalo RR apresenta condu&#231;&#227;o AV discordante espont&#226;nea, caracterizada por <italic>slope</italic> na linha de regress&#227;o TCAV negativa vs. intervalo RR. O desvio padr&#227;o dos intervalos RR e o <italic>slope</italic> da linha de regress&#227;o do TCAV vs. intervalo RR s&#227;o vari&#225;veis explicativas independentes do MET. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <kwd>Atletas</kwd>
        <kwd>Adultos</kwd>
        <kwd>Treinamento de Resist&#234;ncia</kwd>
        <kwd>Aptid&#227;o F&#237;sica</kwd>
        <kwd>Remodela&#231;&#227;o Ventricular</kwd>
        <kwd>Sedentarismo</kwd>
        <kwd>Eletrocardiografia/m&#233;todos</kwd>
        <kwd>Ventr&#237;culos do Cora&#231;&#227;o</kwd>
        <kwd>Fun&#231;&#227;o Ventricular</kwd>
      </kwd-group>
      <counts>
        <fig-count count="4"/>
        <table-count count="4"/>
        <equation-count count="0"/>
        <ref-count count="19"/>
        <page-count count="7"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>A adapta&#231;&#227;o card&#237;aca secund&#225;ria &#224; aptid&#227;o f&#237;sica se reflete na remodela&#231;&#227;o mec&#226;nica, el&#233;trica e auton&#244;mica do cora&#231;&#227;o, como consequ&#234;ncia de repetidas atividades de alta demanda. Atletas bem treinados costumam apresentar discreto ganho de massa ventricular, aumento da amplitude da onda do ECG, repolariza&#231;&#227;o precoce, redu&#231;&#227;o da frequ&#234;ncia card&#237;aca em repouso e aumento da variabilidade da frequ&#234;ncia card&#237;aca, relacionados ao status de condicionamento.<sup><xref ref-type="bibr" rid="B1">1</xref> - <xref ref-type="bibr" rid="B7">7</xref></sup></p>
      <p>Particularmente, a maior parte do remodelamento auton&#244;mico do cora&#231;&#227;o em atletas bem condicionados &#233; consequ&#234;ncia do aumento do t&#244;nus vagal e da estimula&#231;&#227;o simp&#225;tica reduzida sobre o seio e os n&#243;s atrioventriculares (AV).<sup><xref ref-type="bibr" rid="B1">1</xref> , <xref ref-type="bibr" rid="B6">6</xref></sup> Embora o aumento do t&#244;nus vagal possa ser detectado diretamente pela medida da frequ&#234;ncia card&#237;aca em repouso, diferenciar entre o aumento da atividade parassimp&#225;tica sobre o n&#243; sinusal e o n&#243; AV no ECG de superf&#237;cie pode n&#227;o ser t&#227;o simples.</p>
      <p>Frequentemente, atletas de alta demanda apresentam remodelamento do n&#243; atrioventricular (AV), caracterizado por v&#225;rios graus de bloqueio de condu&#231;&#227;o AV, ritmo atrial ou juncional baixo n&#227;o-sinusal e, mais raramente, bloqueio AV completo.<sup><xref ref-type="bibr" rid="B8">8</xref> - <xref ref-type="bibr" rid="B10">10</xref></sup> Esses dist&#250;rbios da condu&#231;&#227;o AV dependem do status do condicionamento f&#237;sico e est&#227;o relacionados n&#227;o apenas ao aumento da atividade parassimp&#225;tica sobre o n&#243; AV, mas tamb&#233;m ao remodelamento secund&#225;rio das fibras do n&#243; AV e ao acoplamento c&#233;lula a c&#233;lula.<sup><xref ref-type="bibr" rid="B11">11</xref> - <xref ref-type="bibr" rid="B13">13</xref></sup></p>
      <p>Embora os dist&#250;rbios da condu&#231;&#227;o AV tenham sido documentados repetidamente em atletas, a adapta&#231;&#227;o din&#226;mica da condu&#231;&#227;o AV ao ciclo card&#237;aco nessa popula&#231;&#227;o ainda precisa de esclarecimentos. Na popula&#231;&#227;o geral, a dura&#231;&#227;o AV varia dinamicamente de acordo com a dura&#231;&#227;o do intervalo RR, caracterizando um efeito semelhante a uma sanfona. Entretanto, em atletas, o remodelamento auton&#244;mico pode influenciar a condu&#231;&#227;o din&#226;mica AV na adapta&#231;&#227;o do intervalo RR, levando a um comportamento distinto da condu&#231;&#227;o AV, em uma resposta &#224; varia&#231;&#227;o do intervalo RR relacionada ao tempo.</p>
      <p>O presente estudo avaliou as variabilidades do tempo de condu&#231;&#227;o AV (TCAV) batimento por batimento e do intervalo RR em corredores de elite e indiv&#237;duos sedent&#225;rios saud&#225;veis, em repouso, com o objetivo de avaliar o efeito do status da aptid&#227;o f&#237;sica na dura&#231;&#227;o do acoplamento espont&#226;neo de TCAV ao intervalo RR.</p>
    </sec>
    <sec sec-type="methods">
      <title>M&#233;todos</title>
      <p>Informa&#231;&#245;es detalhadas sobre o protocolo do estudo, aprova&#231;&#227;o do Comit&#234; de &#201;tica e aquisi&#231;&#227;o de dados do ECG foram descritas em outro artigo.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> O presente estudo analisou dados brutos de ECG de alta resolu&#231;&#227;o do banco de dados de ECG do Programa de Engenharia Biom&#233;dica, utilizando uma nova t&#233;cnica para extra&#231;&#227;o do tempo de condu&#231;&#227;o atrioventricular e intervalos RR.<sup><xref ref-type="bibr" rid="B14">14</xref></sup> O procedimento de amostragem de dados foi descrito em outro artigo.<sup><xref ref-type="bibr" rid="B6">6</xref></sup></p>
      <p>A popula&#231;&#227;o do estudo foi composta por 20 volunt&#225;rios divididos em dois grupos: &#8216;Atleta&#8217;, composto por dez corredores de elite de longa dist&#226;ncia (&#8805; 16,0 equivalentes metab&#243;licos m&#225;ximos [MET]) calculados como o consumo m&#225;ximo de oxig&#234;nio obtido durante o teste de estresse dividido por 3,5 mL&#183;kg<sup>-1</sup>&#183;min<sup>-1</sup>, [m&#233;dia &#177; DP] 19,5 &#177; 1,3 MET; idade 25,1 &#177; 7,1 anos) e &#8216;Controle&#8217;, constitu&#237;do por dez volunt&#225;rios sedent&#225;rios saud&#225;veis do sexo masculino (&#8804; 11,5 MET; 8,7 &#177; 1,9 MET; idade 29,0 &#177; 5,4 anos). Vale ressaltar que o termo &#8216;MET&#8217; &#233; empregado ao longo do texto como o equivalente metab&#243;lico m&#225;ximo alcan&#231;ado durante o teste de estresse. O programa de treinamento dos atletas consistiu em seis a oito sess&#245;es de treinamento / semana; 90 a 120 min / sess&#227;o; 90 a 110 km / semana A detec&#231;&#227;o das ondas e do ponto fiducial foi realizada no ECG realizado com deriva&#231;&#245;es XYZ de Frank modificadas em posi&#231;&#227;o supina em repouso, usando filtro passa-baixa a 15 Hz (Butterworth, 4&#170; ordem). Para a an&#225;lise da dura&#231;&#227;o do intervalo RR, artefatos e batimentos ect&#243;picos foram adequadamente exclu&#237;dos.<sup><xref ref-type="bibr" rid="B15">15</xref> , <xref ref-type="bibr" rid="B16">16</xref></sup></p>
      <p>A dist&#226;ncia entre o pico da onda P e o pico da onda R em batimentos normais definiu o intervalo PR-pico e foi utilizada para analisar a adapta&#231;&#227;o instant&#226;nea do TCAV ao longo do ciclo card&#237;aco.<sup><xref ref-type="bibr" rid="B14">14</xref></sup> O acoplamento PR-pico a intervalos RR foi avaliado batimento a batimento durante todo o registro do ECG, utilizando a deriva&#231;&#227;o que mostra a onda P mais alta, geralmente a deriva&#231;&#227;o Y. O intervalo RR foi avaliado como o tempo entre os picos das ondas R de dois batimentos normais consecutivos. O intervalo PR-pico foi avaliado imediatamente antes do segundo batimento do respectivo intervalo RR. Para cada indiv&#237;duo, foi calculada a m&#233;dia (M) e o desvio padr&#227;o (DP) de todos os intervalos RR normais consecutivos (M-RR e DP-RR) e o respectivo intervalo PR-pico (M-TCAV e DP-TCAV). Os intervalos PR-pico foram correlacionados com os respectivos intervalos RR e o slope (inclina&#231;&#227;o) das linhas de regress&#227;o foi calculado (RR-TCAV<sub>slope</sub>).</p>
      <sec>
        <title>An&#225;lise Estat&#237;stica</title>
        <p>As vari&#225;veis foram expressas como m&#233;dia &#177; DP ou mediana e varia&#231;&#227;o interquartil, quando apropriado. A normalidade dos dados foi avaliada pelo teste de Kolmogorov-Smirnov, e todas as vari&#225;veis analisadas tiveram sua premissa de normalidade aceita. As vari&#225;veis foram comparadas entre os grupos usando o teste <italic>t</italic> de Student n&#227;o pareado. Para avaliar os melhores valores de corte, as curvas ROC foram calculadas a partir do <italic>slope</italic> das linhas de regress&#227;o (TCAV vs. intervalo RR) em ambos os grupos. Um modelo de regress&#227;o linear multivariada foi desenvolvido para explicar o MET com base em par&#226;metros significativos de TCAV e intervalo RR. O coeficiente de correla&#231;&#227;o de Pearson r foi testado quanto &#224; signific&#226;ncia (o n&#237;vel de signific&#226;ncia adotado foi de 5%). Uma condu&#231;&#227;o AV concordante foi arbitrariamente definida como TCAV e o intervalo RR aumentou e diminuiu na mesma dire&#231;&#227;o em ciclos card&#237;acos consecutivos e, de outro modo, foi discordante. O TCAV foi avaliado como intervalo de PR pico.</p>
        <p>Um procedimento de reamostragem de valida&#231;&#227;o de <italic>bootstrap</italic> aplicado ao modelo multivariado foi realizado em duas abordagens diferentes. Na primeira abordagem, 1.100 repeti&#231;&#245;es com substitui&#231;&#227;o foram realizadas em toda a amostra de ambos os grupos para avaliar estimativas m&#233;dias e DP de vari&#225;veis independentes. Em uma segunda abordagem, os dois grupos foram divididos em um grupo de teste, composto por 67% dos indiv&#237;duos de cada grupo, e um grupo de valida&#231;&#227;o, com os 33% restantes. O MET estimado pelo modelo multivariado foi utilizado para classificar Controles e Atletas em todos os conjuntos de procedimentos de <italic>bootstrap</italic> . Os sinais brutos de ECG foram processados utilizando programas personalizados, escritos na linguagem Matlab R2007a (The MathWorks, Inc). A an&#225;lise estat&#237;stica foi realizada utilizando o MS-Excel 360 (Microsoft Corporation) e Medcalc vers&#227;o 11 (Medcalc Software bvba). O n&#237;vel de signific&#226;ncia adotado na an&#225;lise estat&#237;stica foi de 5%.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Resultados</title>
      <p>Os atletas apresentaram valores de M-RR e DP-RR significativamente maiores que os controles, embora sem diferen&#231;as significativas entre os valores de M-TCAV e DP-TCAV ( <xref ref-type="table" rid="t1">Tabela 1</xref> ). Exemplos de indiv&#237;duos dos grupos Controle (a) e Atletas (b) s&#227;o apresentados na <xref ref-type="fig" rid="f01">Figura 1</xref> , onde s&#227;o apresentadas as linhas de regress&#227;o e os respectivos gr&#225;ficos de dispers&#227;o r de TCAV vs. de intervalos RR. O RR-TCAV<sub>slope</sub> &#233; positivo nos Controles ( <xref ref-type="fig" rid="f01">Figura 1-a</xref> ) e negativo nos Atletas ( <xref ref-type="fig" rid="f01">Figura 1-b</xref> ). No geral, o <italic>slope</italic> RR-TCAV nos Controles e Atletas resultou em diferen&#231;as significativas entre os grupos ( <xref ref-type="table" rid="t1">Tabela 1</xref> ).</p>
      <p>
        <table-wrap id="t1">
          <label>Tabela 1</label>
          <caption>
            <title>&#8211; An&#225;lises univariadas das vari&#225;veis estudadas (m&#233;dia &#177; DP)</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="17%">
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead>
              <tr>
                <th align="left" style="font-weight:normal"> </th>
                <th>
                  <italic>M-RR</italic>
                </th>
                <th>
                  <italic>DP-RR</italic>
                </th>
                <th>
                  <italic>M-TCAV</italic>
                </th>
                <th>
                  <italic>DP-TCAV</italic>
                </th>
                <th style="font-weight:normal">
                  <italic>RR-TCAV<sub>slope</sub></italic>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>
                  <bold>Grupo Controle (m&#233;dia &#177; DP)</bold>
                </td>
                <td align="center">853,9 &#177; 94,0</td>
                <td align="center">44,5 &#177; 10,1</td>
                <td align="center">134,0 &#177; 17,7</td>
                <td align="center">2,8 &#177; 1,1</td>
                <td align="center">0,0376 &#177; 0,0219</td>
              </tr>
              <tr>
                <td>
                  <bold>Grupo Atleta (m&#233;dia &#177; DP)</bold>
                </td>
                <td align="center">1079,1 &#177; 207,9</td>
                <td align="center">76,4 &#177; 21,0</td>
                <td align="center">143,3 &#177; 27,6</td>
                <td align="center">3,8 &#177; 2,2</td>
                <td align="center">-0,0034 &#177; 0,0172</td>
              </tr>
              <tr>
                <td>
                  <bold>N&#237;vel de Signific&#226;ncia p</bold>
                </td>
                <td align="center">0,0084</td>
                <td align="center">0,0008</td>
                <td align="center">0,3820</td>
                <td align="center">0,2032</td>
                <td align="center">0,002</td>
              </tr>
              <tr>
                <td>
                  <bold>Estat&#237;sticas ROC</bold>
                </td>
                <td> </td>
                <td> </td>
                <td> </td>
                <td> </td>
                <td> </td>
              </tr>
              <tr>
                <td>&#193;rea sob a curva ROC (AUC)</td>
                <td align="center">0,89</td>
                <td align="center">0,9</td>
                <td align="center">0,56</td>
                <td align="center">0,61</td>
                <td align="center">0,92</td>
              </tr>
              <tr>
                <td>Erro Padr&#227;o</td>
                <td align="center">0,07</td>
                <td align="center">0,08</td>
                <td align="center">0,14</td>
                <td align="center">0,14</td>
                <td align="center">0,06</td>
              </tr>
              <tr>
                <td>Intervalo de Confian&#231;a de 95%</td>
                <td align="center">0,67&#8211;0,98</td>
                <td align="center">0,68&#8211;0,98</td>
                <td align="center">0,32&#8211;0,78</td>
                <td align="center">0,37&#8211;0,82</td>
                <td align="center">0,71&#8211;0,99</td>
              </tr>
              <tr>
                <td>Estat&#237;stica z</td>
                <td align="center">5,5</td>
                <td align="center">5,2</td>
                <td align="center">0,4</td>
                <td align="center">0,8</td>
                <td align="center">6,7</td>
              </tr>
              <tr>
                <td>N&#237;vel de Signific&#226;ncia p (&#225;rea = 0.5)</td>
                <td align="center">&lt; 0,0001</td>
                <td align="center">&lt; 0,0001</td>
                <td align="center">0,6721</td>
                <td align="center">0,4177</td>
                <td align="center">&lt; 0,0001</td>
              </tr>
              <tr>
                <td>Valor de corte</td>
                <td align="center">917,3</td>
                <td align="center">60,9</td>
                <td align="center">124,1</td>
                <td align="center">3,8</td>
                <td align="center">0,0044</td>
              </tr>
              <tr>
                <td>Especificidade</td>
                <td align="center">80%</td>
                <td align="center">100%</td>
                <td align="center">40%</td>
                <td align="center">50%</td>
                <td align="center">100%</td>
              </tr>
              <tr>
                <td>Sensibilidade</td>
                <td align="center">80%</td>
                <td align="center">80%</td>
                <td align="center">90%</td>
                <td align="center">80%</td>
                <td align="center">80%</td>
              </tr>
              <tr>
                <td>Exatid&#227;o</td>
                <td align="center">80%</td>
                <td align="center">90%</td>
                <td align="center">65%</td>
                <td align="center">65%</td>
                <td align="center">90%</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN1">
              <p>
                <italic>M-RR: m&#233;dia de todos os intervalos RR normais; DP-RR: desvio-padr&#227;o de todos os intervalos RR normais; M-TCAV: m&#233;dia dos intervalos de PR-pico correspondentes aos intervalos RR normais; DP-TCAV: desvio padr&#227;o dos intervalos PR-pico respectivos aos intervalos RR normais; RR-TCAV<sub>slope</sub>: slope da linha de regress&#227;o linear entre os intervalos de PR-pico e o respectivo intervalo RR</italic>
              </p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </p>
      <p>
        <fig id="f01">
          <label>Figura 1</label>
          <caption>
            <title>&#8211; <italic>Gr&#225;fico de dispers&#227;o e linha de regress&#227;o do intervalo RR batimento a batimento em fun&#231;&#227;o do respectivo intervalo PR-pico de um indiv&#237;duo Controle de 30 anos (a) e um Atleta de 19 anos de idade (b). Duzentas sequ&#234;ncias de batimentos card&#237;acos das respectivas s&#233;ries de intervalos de pico RR e PR s&#227;o mostradas em (c) e (d). Em (a), o intervalo PR-pico aumenta &#224; medida que o intervalo RR aumenta (slope positivo: 0,0227; r = 0,50; p &lt; 0,01), claramente observado em (c) (condi&#231;&#227;o concordante espont&#226;nea). Por outro lado, em (b), o intervalo PR-pico diminui &#224; medida que o intervalo RR aumenta (slope negativo: -0,0316; r = -0,68; p &lt; 0,01). Em (d), observe per&#237;odos de varia&#231;&#227;o rec&#237;proca nos intervalos de pico RR e PR (condu&#231;&#227;o discordante espont&#226;nea): o intervalo de pico PR diminui &#224; medida que o intervalo RR aumenta (seta pontilhada) e o intervalo PR-pico aumenta &#224; medida que o intervalo RR diminui (condu&#231;&#227;o decremental, seta s&#243;lida) (consulte o texto para mais detalhes).</italic></title>
          </caption>
          <graphic xlink:href="1678-4170-abc-115-01-0071-90281-gf01.tif"/></fig>
      </p>
      <p>As vari&#225;veis que apresentaram diferen&#231;as significativas entre os grupos foram inseridas em um modelo de regress&#227;o linear multivariada, considerando o MET como vari&#225;vel dependente no procedimento bootstrap. DP-RR (p = 0,0099) e RR-TCAV<sub>slope</sub> (p = 0,006) foram vari&#225;veis explicativas independentes do MET, mostrando especificidade de 90%, sensibilidade de 100% e exatid&#227;o total de 95% ( <xref ref-type="table" rid="t2">Tabela 2</xref> ). A estat&#237;stica-C m&#233;dia nos grupos de teste e valida&#231;&#227;o foi, respectivamente, 0,97 &#177; 0,06 e 0,87 &#177; 0,13; p &lt;0,001 para ambos. A an&#225;lise de regress&#227;o linear multivariada e os respectivos resultados dos procedimentos de <italic>bootstrap</italic> est&#227;o resumidos na <xref ref-type="table" rid="t2">Tabela 2</xref> .</p>
      <p>
        <table-wrap id="t2">
          <label>Tabela 2</label>
          <caption>
            <title>&#8211; Modelo explicativo multivari&#225;vel do consumo m&#225;ximo de VO2; 1.100 resultados do procedimento de reamostragem de <italic>bootstrap</italic> e valida&#231;&#227;o interna do modelo explicativo multivari&#225;vel de consumo m&#225;ximo de VO2 usando o &#8216;Teste&#8217; <italic>bootstrap</italic> 2: 1 vs. resultados do procedimento &#8216;Valida&#231;&#227;o&#8217;</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="14%">
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead>
              <tr>
                <th align="left" style="font-weight:normal"> </th>
                <th colspan="2" style="font-weight:normal">Modelo multivariado</th>
                <th colspan="2" style="font-weight:normal">Procedimento de bootstrap</th>
                <th colspan="2" style="font-weight:normal">Teste de bootstrap -valida&#231;&#227;o</th>
              </tr>
              <tr>
                <th align="left" colspan="7" style="font-weight:normal">
                  <hr/>
                </th>
              </tr>
              <tr>
                <th align="left" style="font-weight:normal">Vari&#225;veis do Modelo</th>
                <th style="font-weight:normal">Coeficientes &#177;</th>
                <th>
                  <italic>p</italic>
                </th>
                <th style="font-weight:normal">Coeficientes &#177;</th>
                <th>
                  <italic>p</italic>
                </th>
                <th style="font-weight:normal">Coeficientes &#177;</th>
                <th>
                  <italic>p</italic>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>
                  <bold><italic>Slope</italic> PR a RR (15 Hz)</bold>
                </td>
                <td align="center">-100,36 &#177; 31,97</td>
                <td align="center">0,006</td>
                <td align="center">-105,76 &#177; 33,93</td>
                <td align="center">0,0009</td>
                <td align="center">-101,42 &#177; 29,39</td>
                <td align="center">0,0003</td>
              </tr>
              <tr>
                <td>
                  <bold>DP-RR</bold>
                </td>
                <td align="center">0,115 &#177; 0,040</td>
                <td align="center">0,0099</td>
                <td align="center">0,115 &#177; 0,041</td>
                <td align="center">0,003</td>
                <td align="center">0,115 &#177; 0,036</td>
                <td align="center">0,0007</td>
              </tr>
              <tr>
                <td>
                  <bold>Constante</bold>
                </td>
                <td align="center">8,88</td>
                <td align="center"> </td>
                <td align="center">8,75 &#177; 3,22</td>
                <td align="center">0,003</td>
                <td align="center">8,85 &#177; 2,83</td>
                <td align="center">0,0009</td>
              </tr>
              <tr>
                <td>Estat&#237;sticas ROC</td>
                <td align="center"> </td>
                <td align="center"> </td>
                <td align="center"> </td>
                <td align="center"> </td>
                <td align="center">Grupo Teste</td>
                <td align="center">Grupo Valida&#231;a&#245;</td>
              </tr>
              <tr>
                <td>&#193;rea sob a curva ROC (AUC)</td>
                <td align="center">0,99</td>
                <td> </td>
                <td align="center">0,99</td>
                <td> </td>
                <td align="center">0,97</td>
                <td align="center">0,87</td>
              </tr>
              <tr>
                <td>Erro Padr&#227;o</td>
                <td align="center">0,02</td>
                <td> </td>
                <td align="center">0,02</td>
                <td> </td>
                <td align="center">0,06</td>
                <td align="center">0,13</td>
              </tr>
              <tr>
                <td>Intervalo de Confian&#231;a de 95%</td>
                <td align="center">0,94&#8211;1,00</td>
                <td> </td>
                <td align="center">0,94&#8211;1,00</td>
                <td> </td>
                <td align="center">0,85&#8211;1,00</td>
                <td align="center">0,61&#8211;1,00</td>
              </tr>
              <tr>
                <td>Estat&#237;stica z</td>
                <td align="center">42,1</td>
                <td> </td>
                <td align="center">42,1</td>
                <td> </td>
                <td align="center">16,7</td>
                <td align="center">6,5</td>
              </tr>
              <tr>
                <td>N&#237;vel de Signific&#226;ncia <italic>p</italic> (&#225;rea = 0,5)</td>
                <td align="center">&lt; 0,001</td>
                <td> </td>
                <td align="center">&lt; 0,001</td>
                <td> </td>
                <td align="center">&lt; 0,001</td>
                <td align="center">&lt; 0,001</td>
              </tr>
              <tr>
                <td>Valor de corte</td>
                <td align="center">12,3</td>
                <td> </td>
                <td align="center">12,0</td>
                <td> </td>
                <td align="center">14,2</td>
                <td> </td>
              </tr>
              <tr>
                <td>Especificidade</td>
                <td align="center">90%</td>
                <td> </td>
                <td align="center">90%</td>
                <td> </td>
                <td align="center">90,2%</td>
                <td align="center">81,0%</td>
              </tr>
              <tr>
                <td>Sensibilidade</td>
                <td align="center">100%</td>
                <td> </td>
                <td align="center">100%</td>
                <td> </td>
                <td align="center">96,7%</td>
                <td align="center">80,4%</td>
              </tr>
              <tr>
                <td>Exatid&#227;o total</td>
                <td align="center">95%</td>
                <td> </td>
                <td align="center">95%</td>
                <td> </td>
                <td align="center">93,4%</td>
                <td align="center">80,7%</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN2">
              <p>
                <italic>* Procedimento de bootstrap realizado sem restitui&#231;&#227;o. O modelo explicativo multivariado foi calculado no grupo Teste e validado no grupo Valida&#231;&#227;o; &#177; = (m&#233;dia &#177; DP).</italic>
              </p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </p>
      <p>Os valores de RR-TCAV<sub>slope</sub> para cada grupo, incluindo faixa interquartil e intervalos de confian&#231;a (IC) de 95%, s&#227;o mostrados na <xref ref-type="fig" rid="f02">figura 2-a</xref> . A sensibilidade, a especificidade e a exatid&#227;o total foram calculadas utilizando-se o valor de corte ideal apresentado na <xref ref-type="table" rid="t1">tabela 1</xref> e exibido como inser&#231;&#227;o. Para enfatizar a associa&#231;&#227;o entre condu&#231;&#227;o decremental espont&#226;nea e status f&#237;sico, uma linha de regress&#227;o de RR-TCAV<sub>slope</sub> vs. MET &#233; apresentada na <xref ref-type="fig" rid="f02">figura 2-a</xref> . Ela mostra correla&#231;&#227;o significativa (r = 0,70; p &lt; 0,05) e slope negativo, demonstrando que o RR-TCAV<sub>slope</sub> diminui &#224; medida que o MET aumenta. Um exemplo de uma curta sequ&#234;ncia de batimentos sinusais mostrando condu&#231;&#227;o decremental espont&#226;nea, registrada durante o repouso em posi&#231;&#227;o supina em um atleta de 19 anos (MET 16,8 METs) &#233; mostrado na <xref ref-type="fig" rid="f02">Figura 2-b</xref> .</p>
      <p>
        <fig id="f02">
          <label>Figura 2</label>
          <caption>
            <title>&#8211; <italic>(a) Valores do slope da linha de regress&#227;o do TCAV combinado vs. intervalos RR m&#233;dios (RR-TCAV<sub>slope</sub>) em fun&#231;&#227;o do consumo de VO2 expresso como equivalente metab&#243;lico m&#225;ximo (MET) alcan&#231;ado durante o teste de estresse e o respectivo gr&#225;fico boxplot. Observe que o RR-TCAV<sub>slope</sub> tende a ser mais negativo &#224; medida que o status do condicionamento f&#237;sico aumenta (pontos cinzas), em compara&#231;&#227;o com indiv&#237;duos sedent&#225;rios (pontos brancos). Gr&#225;ficos boxplot mostrando mediana, intervalo interquartil e intervalos de confian&#231;a de 95% s&#227;o mostrados nas proximidades dos respectivos pontos do grupo. Os valores de especificidade, sensibilidade e exatid&#227;o foram calculados utilizando-se o RR-TCAV<sub>slope</sub> = 0,0044 como crit&#233;rio de corte. (b) Ilustra&#231;&#227;o do segmento de ECG de atleta de 19 anos, representando uma sequ&#234;ncia de batimentos sinusais normais, mostrando o alongamento do TCAV &#224; medida que o intervalo RR diminui, indicando condu&#231;&#227;o AV decremental. Observe os picos de onda P e onda R tomados como pontos fiduciais para avalia&#231;&#227;o do intervalo PR-pico. O TCAV foi avaliado como intervalo de PR-pico. TCAV - tempo de condu&#231;&#227;o atrioventricular (veja o texto para maiores detalhes).</italic></title>
          </caption>
          <graphic xlink:href="1678-4170-abc-115-01-0071-90281-gf02.tif"/></fig>
      </p>
    </sec>
    <sec sec-type="discussion">
      <title>Discuss&#227;o</title>
      <p>A condu&#231;&#227;o ventricular atrial &#233; o determinante mais importante da dura&#231;&#227;o do intervalo PR, que sofre flutua&#231;&#245;es din&#226;micas, dependendo dos estados auton&#244;micos e de sa&#250;de, idade, FC instant&#226;nea, medicamentos, postura e frequ&#234;ncia respirat&#243;ria.<sup><xref ref-type="bibr" rid="B17">17</xref></sup> A avalia&#231;&#227;o do intervalo PR utilizando as abordagens de in&#237;cio de onda P de ou pico de onda P como pontos fiduciais demonstraram fornecer resultados concisos e precisos e, portanto, ambos s&#227;o apropriados para avaliar as varia&#231;&#245;es de TCAV inter-batimentos.<sup><xref ref-type="bibr" rid="B14">14</xref> - <xref ref-type="bibr" rid="B17">17</xref></sup></p>
      <p>No presente estudo, corredores de longa dist&#226;ncia altamente treinados e indiv&#237;duos sedent&#225;rios saud&#225;veis tiveram sua pot&#234;ncia aer&#243;bica m&#225;xima avaliada e a variabilidade do TCAV acoplado ao intervalo RR anterior avaliada no ECG em repouso na posi&#231;&#227;o supina. Foi levantada a hip&#243;tese de que, em repouso, a condu&#231;&#227;o AV seria afetada pela remodela&#231;&#227;o AV induzida por treinamento avan&#231;ado, fazendo com que o acoplamento do TCAV ao intervalo RR se comportasse de maneira diferente das condi&#231;&#245;es sedent&#225;rias. Em um modelo linear, o acoplamento de TCAV ao intervalo RR mostrou um <italic>slope</italic> m&#233;dio negativo da linha de regress&#227;o no grupo Atleta e, inversamente, um <italic>slope</italic> m&#233;dio positivo no grupo Controle, indicando que a remodela&#231;&#227;o do n&#243; AV devido ao treinamento induz aumento decrescente da condu&#231;&#227;o. Uma medida potencialmente distinta da aptid&#227;o f&#237;sica, o <italic>slope</italic> de regress&#227;o do TCAV para o intervalo RR identificou corretamente 90% do status de aptid&#227;o f&#237;sica de todos os indiv&#237;duos. Embora a identifica&#231;&#227;o de condu&#231;&#227;o decremental em atletas seja um achado comum, que seja de nosso conhecimento, a aplica&#231;&#227;o de uma modelagem linear para quantificar TCAV e sua rela&#231;&#227;o com o intervalo RR em atletas altamente treinados ainda n&#227;o foi relatada.</p>
      <p>Estudos anteriores demonstraram uma alta preval&#234;ncia de bloqueio AV Mobitz I de 2&#186; grau em corredores de longa dist&#226;ncia em repouso.<sup><xref ref-type="bibr" rid="B8">8</xref> - <xref ref-type="bibr" rid="B10">10</xref></sup> No presente estudo, a ocorr&#234;ncia de alongamento espont&#226;neo do intervalo PR-pico relacionado ao encurtamento do intervalo RR foi um achado importante, tornando o <italic>slope</italic> m&#233;dio negativo no grupo Atletas ( <xref ref-type="fig" rid="f02">Figura 2b</xref> ). Ao contr&#225;rio desses estudos, nenhuma onda P bloqueada foi encontrada ap&#243;s uma revis&#227;o cuidadosa dos sinais. Epis&#243;dios espont&#226;neos de condu&#231;&#227;o decremental foram frequentes no grupo de Atletas (57,9% do tempo agregado de registro no ECG de Atletas) e raros no grupo Controle (7,9% do tempo agregado de registro no ECG dos Controles). Al&#233;m disso, quando o slope de regress&#227;o de TCAV vs. intervalo RR foi plotado contra MET, observou-se que quanto maior o MET, mais negativo era o RR-TCAV<sub>slope</sub>, mostrando que a condu&#231;&#227;o AV decremental espont&#226;nea se torna mais frequente &#224; medida que o status do condicionamento f&#237;sico melhora ( <xref ref-type="fig" rid="f02">Figura 2a</xref> ) . Destaca-se que a condu&#231;&#227;o decremental foi mais frequentemente observada quando o intervalo RR foi superior a 1.022,0 ms. A redu&#231;&#227;o do intervalo PR-pico relacionada ao aumento do intervalo RR tamb&#233;m foi observada nos atletas ( <xref ref-type="fig" rid="f02">Figura 1d</xref> ). Uma poss&#237;vel explica&#231;&#227;o para esse &#250;ltimo achado &#233; a ocorr&#234;ncia comum de atividade de estimula&#231;&#227;o espont&#226;nea para-sinusal induzida vagalmente.</p>
      <p>Foi demonstrado que o ECG de repouso de atletas de resist&#234;ncia pode mostrar caracter&#237;sticas distintas de indiv&#237;duos sedent&#225;rios saud&#225;veis demograficamente equivalentes, tendo semelhan&#231;as com aquelas observadas em idosos e / ou pacientes com doen&#231;a cardiovascular.<sup><xref ref-type="bibr" rid="B18">18</xref></sup> Entretanto, em atletas, as anormalidades da condu&#231;&#227;o AV t&#234;m sido relacionadas a maior atividade parassimp&#225;tica, diferentemente dos idosos.<sup><xref ref-type="bibr" rid="B19">19</xref></sup> Estudos atuais t&#234;m demonstrado que o treinamento atl&#233;tico pode induzir adapta&#231;&#245;es fisiol&#243;gicas intr&#237;nsecas no sistema de condu&#231;&#227;o, contribuindo para a maior preval&#234;ncia de anormalidades na condu&#231;&#227;o AV.<sup><xref ref-type="bibr" rid="B11">11</xref> - <xref ref-type="bibr" rid="B13">13</xref></sup> Os mecanismos fisiol&#243;gicos pelos quais o treinamento de resist&#234;ncia induz essas altera&#231;&#245;es intr&#237;nsecas no sistema de condu&#231;&#227;o card&#237;aca apresentam entendimento limitado e podem ser multifatoriais, mas altera&#231;&#245;es anat&#244;micas, como dilata&#231;&#227;o atrial e ventricular, demonstraram a cria&#231;&#227;o de um remodelamento mec&#226;nico-el&#233;trico necess&#225;rio para causar adapta&#231;&#245;es eletrofisiol&#243;gicas AV intr&#237;nsecas.<sup><xref ref-type="bibr" rid="B7">7</xref> , <xref ref-type="bibr" rid="B11">11</xref></sup></p>
      <p>As limita&#231;&#245;es do presente estudo incluem o tamanho da amostra de dois grupos distintos em rela&#231;&#227;o ao status de condicionamento f&#237;sico. Os sinais brutos do ECG foram obtidos no banco de dados de ECG dispon&#237;vel no Programa de Engenharia Biom&#233;dica (amostra de conveni&#234;ncia). O intervalo Pico-P ao Pico-R foi utilizado como substituto da medida convencional do intervalo PR. Embora tenha sido demonstrado que o intervalo Pico-P ao Pico-R adequadamente descreve a dinamicidade do intervalo PR, a real dura&#231;&#227;o do intervalo PR pode ser maior do que a observada no presente estudo. Observou-se que tanto a M-TCAV quanto o DP-TCAV foram maiores nos atletas quando comparados aos controles, embora a signific&#226;ncia estat&#237;stica n&#227;o tenha sido alcan&#231;ada. A explica&#231;&#227;o para esse achado pode ser dupla: i) embora se esperasse que a variabilidade do TCAV fosse maior entre os atletas, nenhum bloqueio Mobitz I verdadeiro foi observado ap&#243;s uma cuidadosa revis&#227;o do sinal. Isso indica que era esperado que a variabilidade do TCAV aumentasse at&#233; um certo limite e ii) o tamanho da amostra atual foi projetado para determinar diferen&#231;as relacionadas &#224; energia total da ativa&#231;&#227;o ventricular<sup><xref ref-type="bibr" rid="B6">6</xref></sup> , limitando assim seu poder estat&#237;stico para detectar a varia&#231;&#227;o do TCAV entre os grupos. Os indiv&#237;duos foram mantidos em repouso em posi&#231;&#227;o supina por 10 minutos antes da aquisi&#231;&#227;o do ECG, com o objetivo de impedir que o efeito da mem&#243;ria ortost&#225;tica na condu&#231;&#227;o AV influenciasse a condu&#231;&#227;o AV na dinamicidade do acoplamento ao intervalo RR, em um ambiente com temperatura controlada e isolado acusticamente. No entanto, n&#227;o se pode excluir completamente o fato de que algum efeito de mem&#243;ria ortost&#225;tica ainda pudesse estar presente. Neste estudo, observou-se a ocorr&#234;ncia de aumento espont&#226;neo do intervalo PR-pico &#224; medida que o intervalo RR diminuiu e vice-versa. Esse fen&#244;meno foi interpretado como uma manifesta&#231;&#227;o de condu&#231;&#227;o decremental durante o tr&#226;nsito da frente de onda da ativa&#231;&#227;o card&#237;aca atrav&#233;s do n&#243; AV. No entanto, devido &#224; natureza deste estudo, nenhum teste eletrofisiol&#243;gico invasivo foi realizado para melhor caracterizar a condu&#231;&#227;o decremental ou a atividade de estimula&#231;&#227;o para-sinusal. Ainda &#233; necess&#225;rio investigar o potencial impacto dos achados atuais em contextos cl&#237;nicos, como um marcador para taquiarritmias supraventriculares, particularmente a arritmia reentrante do n&#243; AV e fibrila&#231;&#227;o atrial.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclus&#227;o</title>
      <p>O n&#243; atrioventricular apresenta remodela&#231;&#227;o fisiol&#243;gica substancial em corredores de longa dist&#226;ncia de elite, caracterizada por condu&#231;&#227;o AV decremental espont&#226;nea em repouso na posi&#231;&#227;o supina, raramente observada em indiv&#237;duos sedent&#225;rios saud&#225;veis nas mesmas condi&#231;&#245;es de repouso. O <italic>slope</italic> da linha de regress&#227;o linear do acoplamento PR-pico ao intervalo RR &#233; uma vari&#225;vel explicativa forte e independente do equivalente metab&#243;lico m&#225;ximo alcan&#231;ado durante o teste de estresse nessa popula&#231;&#227;o.</p>
    </sec>
  </body>
  <back>
    <ack>
      <title>Agradecimento</title>
      <p>Agradecemos a Dr. Moacir Marocolo que realizou o recrutamento dos sujeitos do estudo e a capta&#231;&#227;o dos sinais de ECG, que foram inclu&#237;dos no banco de dados de ECG do Programa de Engenharia Biom&#233;dica. A capta&#231;&#227;o dos sinais de ECG foi realizada com a participa&#231;&#227;o e sob orienta&#231;&#227;o presencial do Dr. Paulo Roberto Benchimol-Barbosa.</p>
    </ack>
    <ref-list>
      <title>Refer&#234;ncias</title>
      <ref id="B1">
        <label>1</label>
        <mixed-citation>1. Melanson EL, Freedson PS. The effect of endurance training on resting heart rate variability in sedentary adult males. Eur J Appl Physiol. 2001;85(5):442-9.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Melanson</surname>
              <given-names>EL</given-names>
            </name>
            <name>
              <surname>Freedson</surname>
              <given-names>PS</given-names>
            </name>
          </person-group>
          <article-title>The effect of endurance training on resting heart rate variability in sedentary adult males</article-title>
          <source>Eur J Appl Physiol</source>
          <year>2001</year>
          <volume>85</volume>
          <issue>5</issue>
          <fpage>442</fpage>
          <lpage>449</lpage>
        </element-citation>
      </ref>
      <ref id="B2">
        <label>2</label>
        <mixed-citation>2. wasaki K, Zhang R, Zuckerman JH, Levine BD. Dose-response relationship of the cardiovascular adaptation to endurance training in healthy adults: how much training for what benefit? J Appl Physiol. 2003;95(4):1575-83.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>wasaki</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Zhang</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Zuckerman</surname>
              <given-names>JH</given-names>
            </name>
            <name>
              <surname>Levine</surname>
              <given-names>BD</given-names>
            </name>
          </person-group>
          <article-title>Dose-response relationship of the cardiovascular adaptation to endurance training in healthy adults: how much training for what benefit?</article-title>
          <source>J Appl Physiol</source>
          <year>2003</year>
          <volume>95</volume>
          <issue>4</issue>
          <fpage>1575</fpage>
          <lpage>1583</lpage>
        </element-citation>
      </ref>
      <ref id="B3">
        <label>3</label>
        <mixed-citation>3. Haigney MC, Zareba W, Gentlesk PJ, Goldstein RE, Illovsky M, McNitt S, et al. QT interval variability and spontaneous ventricular tachycardia or fibrillation in the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II patients. J Am Coll Cardiol.. 2004;44(7):1481-7.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Haigney</surname>
              <given-names>MC</given-names>
            </name>
            <name>
              <surname>Zareba</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>Gentlesk</surname>
              <given-names>PJ</given-names>
            </name>
            <name>
              <surname>Goldstein</surname>
              <given-names>RE</given-names>
            </name>
            <name>
              <surname>Illovsky</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>McNitt</surname>
              <given-names>S</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>QT interval variability and spontaneous ventricular tachycardia or fibrillation in the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II patients</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2004</year>
          <volume>44</volume>
          <issue>7</issue>
          <fpage>1481</fpage>
          <lpage>1487</lpage>
        </element-citation>
      </ref>
      <ref id="B4">
        <label>4</label>
        <mixed-citation>4. Maskhulia L, Chabashvili N, Akhalkatsi V, Chutkerashvili T. Left ventricular morphological changes due to vigorous physical activity in highly trained football players and wrestlers: relationship with aerobic capacity. Georgian Med News. 2006;133:68-71.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Maskhulia</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Chabashvili</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Akhalkatsi</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Chutkerashvili</surname>
              <given-names>T</given-names>
            </name>
          </person-group>
          <article-title>Left ventricular morphological changes due to vigorous physical activity in highly trained football players and wrestlers: relationship with aerobic capacity</article-title>
          <source>Georgian Med News</source>
          <year>2006</year>
          <volume>133</volume>
          <fpage>68</fpage>
          <lpage>71</lpage>
        </element-citation>
      </ref>
      <ref id="B5">
        <label>5</label>
        <mixed-citation>5. Atchley AE Jr, Douglas PS. Left ventricular hypertrophy in athletes: morphologic features and clinical correlates. Cardiol Clin. 2007;25(3):371-82.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Atchley</surname>
              <given-names>AE</given-names>
              <suffix>Jr</suffix>
            </name>
            <name>
              <surname>Douglas</surname>
              <given-names>PS</given-names>
            </name>
          </person-group>
          <article-title>Left ventricular hypertrophy in athletes: morphologic features and clinical correlates</article-title>
          <source>Cardiol Clin</source>
          <year>2007</year>
          <volume>25</volume>
          <issue>3</issue>
          <fpage>371</fpage>
          <lpage>382</lpage>
        </element-citation>
      </ref>
      <ref id="B6">
        <label>6</label>
        <mixed-citation>6. Marocolo M, Nadal J, Benchimol-Barbosa PR. The effect of an aerobic training program on the electrical remodeling of heart high-frequency components of the signal-averaged electrocardiogram is a predictor of the maximal aerobic power. Braz J Med Biol Res. 2007;40(2):199-208.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Marocolo</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Nadal</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Benchimol-Barbosa</surname>
              <given-names>PR</given-names>
            </name>
          </person-group>
          <article-title>The effect of an aerobic training program on the electrical remodeling of heart high-frequency components of the signal-averaged electrocardiogram is a predictor of the maximal aerobic power</article-title>
          <source>Braz J Med Biol Res</source>
          <year>2007</year>
          <volume>40</volume>
          <issue>2</issue>
          <fpage>199</fpage>
          <lpage>208</lpage>
        </element-citation>
      </ref>
      <ref id="B7">
        <label>7</label>
        <mixed-citation>7. Barbosa EC, Bomfim Ade S, Benchimol-Barbosa PR, Ginefra P. Ionic mechanisms and vectorial model of early repolarization pattern in the surface electrocardiogram of the athlete. Ann Noninvasive Electrocardiol. 2008;13(3):301-7.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Barbosa</surname>
              <given-names>EC</given-names>
            </name>
            <name>
              <surname>Bomfim Ade</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Benchimol-Barbosa</surname>
              <given-names>PR</given-names>
            </name>
            <name>
              <surname>Ginefra</surname>
              <given-names>P</given-names>
            </name>
          </person-group>
          <article-title>Ionic mechanisms and vectorial model of early repolarization pattern in the surface electrocardiogram of the athlete</article-title>
          <source>Ann Noninvasive Electrocardiol</source>
          <year>2008</year>
          <volume>13</volume>
          <issue>3</issue>
          <fpage>301</fpage>
          <lpage>307</lpage>
        </element-citation>
      </ref>
      <ref id="B8">
        <label>8</label>
        <mixed-citation>8. Hanne-Paparo N, Kellermann JJ. Long-term Holter ECG monitoring of athletes. Med Sci Sports Exerc. 1981;13(5):294-8.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Hanne-Paparo</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Kellermann</surname>
              <given-names>JJ</given-names>
            </name>
          </person-group>
          <article-title>Long-term Holter ECG monitoring of athletes</article-title>
          <source>Med Sci Sports Exerc</source>
          <year>1981</year>
          <volume>13</volume>
          <issue>5</issue>
          <fpage>294</fpage>
          <lpage>298</lpage>
        </element-citation>
      </ref>
      <ref id="B9">
        <label>9</label>
        <mixed-citation>9. Vitasalo MT, Kala R, Eisalo A. Ambulatory electrocardiographic recording in endurance athletes. Br Heart J. 1982;47(3):213-20.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Vitasalo</surname>
              <given-names>MT</given-names>
            </name>
            <name>
              <surname>Kala</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Eisalo</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
          <article-title>Ambulatory electrocardiographic recording in endurance athletes</article-title>
          <source>Br Heart J</source>
          <year>1982</year>
          <volume>47</volume>
          <issue>3</issue>
          <fpage>213</fpage>
          <lpage>220</lpage>
        </element-citation>
      </ref>
      <ref id="B10">
        <label>10</label>
        <mixed-citation>10. Barold SS. Type I Wenckebach second-degree AV block: A matter of definition. Clin Cardiol. 2018;41(3):282-4.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Barold</surname>
              <given-names>SS</given-names>
            </name>
          </person-group>
          <article-title>Type I Wenckebach second-degree AV block: A matter of definition</article-title>
          <source>Clin Cardiol</source>
          <year>2018</year>
          <volume>41</volume>
          <issue>3</issue>
          <fpage>282</fpage>
          <lpage>284</lpage>
        </element-citation>
      </ref>
      <ref id="B11">
        <label>11</label>
        <mixed-citation>11. Stein R, Moraes RS, Cavalcanti AV, Ferlin EL, Zimerman LI, Ribeiro JP. Atrial automaticity and atrioventricular conduction in athletes: contribution of autonomic regulation. Eur J Appl Physiol. 2000;82(1-2):155-7.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Stein</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Moraes</surname>
              <given-names>RS</given-names>
            </name>
            <name>
              <surname>Cavalcanti</surname>
              <given-names>AV</given-names>
            </name>
            <name>
              <surname>Ferlin</surname>
              <given-names>EL</given-names>
            </name>
            <name>
              <surname>Zimerman</surname>
              <given-names>LI</given-names>
            </name>
            <name>
              <surname>Ribeiro</surname>
              <given-names>JP</given-names>
            </name>
          </person-group>
          <article-title>Atrial automaticity and atrioventricular conduction in athletes: contribution of autonomic regulation</article-title>
          <source>Eur J Appl Physiol</source>
          <year>2000</year>
          <volume>82</volume>
          <issue>1-2</issue>
          <fpage>155</fpage>
          <lpage>157</lpage>
        </element-citation>
      </ref>
      <ref id="B12">
        <label>12</label>
        <mixed-citation>12. Stein R, Medeiros CM, Rosito GA, Zimerman LI, Ribeiro JP. Intrinsic sinus and atrioventricular node electrophysiologic adaptations in endurance athletes. J Am Coll Cardiol. 2002;39(6):1033-8.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Stein</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Medeiros</surname>
              <given-names>CM</given-names>
            </name>
            <name>
              <surname>Rosito</surname>
              <given-names>GA</given-names>
            </name>
            <name>
              <surname>Zimerman</surname>
              <given-names>LI</given-names>
            </name>
            <name>
              <surname>Ribeiro</surname>
              <given-names>JP</given-names>
            </name>
          </person-group>
          <article-title>Intrinsic sinus and atrioventricular node electrophysiologic adaptations in endurance athletes</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2002</year>
          <volume>39</volume>
          <issue>6</issue>
          <fpage>1033</fpage>
          <lpage>1038</lpage>
        </element-citation>
      </ref>
      <ref id="B13">
        <label>13</label>
        <mixed-citation>13. Santos M, Pinheiro-Vieira A, Hip&#243;lito-Reis A. Bradycardia in the athlete: don&#8217;t always blame the autonomic system! Europace. 2013;15(11):1650.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Santos</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Pinheiro-Vieira</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Hip&#243;lito-Reis</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
          <article-title>Bradycardia in the athlete: don&#8217;t always blame the autonomic system!</article-title>
          <source>Europace</source>
          <year>2013</year>
          <volume>15</volume>
          <issue>11</issue>
          <size units="pages">1650</size>
        </element-citation>
      </ref>
      <ref id="B14">
        <label>14</label>
        <mixed-citation>14. Nasario-Junior O, Benchimol-Barbosa PR, Pedrosa RC, Nadal J. Validity of P-peak to R-peak interval compared to classical PR-interval to assess dynamic beat-to-beat AV conduction variability on surface electrocardiogram. Biomed Phys Eng Express. 2018;4(3):035037.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Nasario</surname>
              <given-names>O</given-names>
              <suffix>Junior</suffix>
            </name>
            <name>
              <surname>Benchimol-Barbosa</surname>
              <given-names>PR</given-names>
            </name>
            <name>
              <surname>Pedrosa</surname>
              <given-names>RC</given-names>
            </name>
            <name>
              <surname>Nadal</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Validity of P-peak to R-peak interval compared to classical PR-interval to assess dynamic beat-to-beat AV conduction variability on surface electrocardiogram</article-title>
          <source>Biomed Phys Eng Express</source>
          <year>2018</year>
          <volume>4</volume>
          <issue>3</issue>
          <elocation-id>035037</elocation-id>
        </element-citation>
      </ref>
      <ref id="B15">
        <label>15</label>
        <mixed-citation>15. Nasario-Junior O, Benchimol-Barbosa PR, Nadal J. Refining the deceleration capacity index in phase-rectified signal averaging to assess physical conditioning level. J Electrocardiol. 2014;47(3):306-10.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Nasario</surname>
              <given-names>O</given-names>
              <suffix>Junior</suffix>
            </name>
            <name>
              <surname>Benchimol-Barbosa</surname>
              <given-names>PR</given-names>
            </name>
            <name>
              <surname>Nadal</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Refining the deceleration capacity index in phase-rectified signal averaging to assess physical conditioning level</article-title>
          <source>J Electrocardiol</source>
          <year>2014</year>
          <volume>47</volume>
          <issue>3</issue>
          <fpage>306</fpage>
          <lpage>310</lpage>
        </element-citation>
      </ref>
      <ref id="B16">
        <label>16</label>
        <mixed-citation>16. Nasario-Junior O, Benchimol-Barbosa PR, Pedrosa RC, Nadal J. Assessment of autonomic function by phase rectification of RR interval histogram analysis in Chagas disease. Arq Bras Cardiol. 2015;104(6):450-5.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Nasario</surname>
              <given-names>O</given-names>
              <suffix>Junior</suffix>
            </name>
            <name>
              <surname>Benchimol-Barbosa</surname>
              <given-names>PR</given-names>
            </name>
            <name>
              <surname>Pedrosa</surname>
              <given-names>RC</given-names>
            </name>
            <name>
              <surname>Nadal</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Assessment of autonomic function by phase rectification of RR interval histogram analysis in Chagas disease</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2015</year>
          <volume>104</volume>
          <issue>6</issue>
          <fpage>450</fpage>
          <lpage>455</lpage>
        </element-citation>
      </ref>
      <ref id="B17">
        <label>17</label>
        <mixed-citation>17. Forester J, Bo H, Sleigh J Wand Henderson JD. Variability of R-R, P wave-to-R wave, and R wave-to-T wave intervals. Am J Physiol. 1997;273(6):H2857-60.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Forester</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Bo</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Sleigh</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Wand Henderson</surname>
              <given-names>JD</given-names>
            </name>
          </person-group>
          <article-title>Variability of R-R, P wave-to-R wave, and R wave-to-T wave intervals</article-title>
          <source>Am J Physiol</source>
          <year>1997</year>
          <volume>273</volume>
          <issue>6</issue>
          <fpage>H2857</fpage>
          <lpage>H2860</lpage>
        </element-citation>
      </ref>
      <ref id="B18">
        <label>18</label>
        <mixed-citation>18. Zehender M, Meinertz T, Keul J, Just H. ECG variants and cardiac arrhythmias in athletes: clinical relevance and prognostic importance. Am Heart J. 1990;119(6):1378-90.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Zehender</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Meinertz</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Keul</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Just</surname>
              <given-names>H</given-names>
            </name>
          </person-group>
          <article-title>ECG variants and cardiac arrhythmias in athletes: clinical relevance and prognostic importance</article-title>
          <source>Am Heart J</source>
          <year>1990</year>
          <volume>119</volume>
          <issue>6</issue>
          <fpage>1378</fpage>
          <lpage>1390</lpage>
        </element-citation>
      </ref>
      <ref id="B19">
        <label>19</label>
        <mixed-citation>19. Drezner JA, Fischbach P, Froelicher V, Marek J, Pelliccia A, Prutkin JM, et al. Normal electrocardiographic findings: recognising physiological adaptations in athletes. Br J Sports Med. 2013;47(3):125-36.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Drezner</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Fischbach</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Froelicher</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Marek</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Pelliccia</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Prutkin</surname>
              <given-names>JM</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Normal electrocardiographic findings: recognising physiological adaptations in athletes</article-title>
          <source>Br J Sports Med</source>
          <year>2013</year>
          <volume>47</volume>
          <issue>3</issue>
          <fpage>125</fpage>
          <lpage>136</lpage>
        </element-citation>
      </ref>
    </ref-list>
    <fn-group>
      <fn fn-type="other">
        <p>Vincula&#231;&#227;o Acad&#234;mica</p>
        <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
      </fn>
      <fn fn-type="other">
        <p>Aprova&#231;&#227;o &#233;tica e consentimento informado</p>
        <p>Este estudo foi aprovado pelo Comit&#234; de &#201;tica do Instituto Nacional de Cardiologia sob o n&#250;mero de protocolo 0026/20.02.04. Todos os procedimentos envolvidos nesse estudo est&#227;o de acordo com a Declara&#231;&#227;o de Helsinki de 1975, atualizada em 2013. O consentimento informado foi obtido de todos os participantes inclu&#237;dos no estudo.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Errata</bold>
        </p>
        <p>
          <bold>Ahead of Print</bold>
        </p>
        <p> No artigo original publicado em ahead of print com o t&#237;tulo &#8220;Avalia&#231;&#227;o do Tempo de Condu&#231;&#227;o Atrioventricular Din&#226;mica para Acoplamento ao Intervalo RR em Atletas e Indiv&#237;duos Sedent&#225;rios&#8221;, com n&#250;mero de DOI: https://doi.org/10.36660/ abc.20190281, publicado no peri&#243;dico Arquivos Brasileiros de Cardiologia, considerar correto o t&#237;tulo &#8220;Avalia&#231;&#227;o da Din&#226;mica do Acoplamento da Condu&#231;&#227;o Atrioventricular &#224; Varia&#231;&#227;o dos Intervalos RR em Atletas e Indiv&#237;duos Sedent&#225;rios&#8221;.</p>
      </fn>
    </fn-group>
    <fn-group>
      <fn fn-type="supported-by">
        <p>Fontes de Financiamento</p>
        <p>O presente estudo foi financiado por FINEP, CNPq e CAPES.</p>
      </fn>
    </fn-group>
  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Assessing Dynamic Atrioventricular Conduction Time to RR-interval Coupling in Athletes and Sedentary Subjects</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-4782-822X</contrib-id>
          <name>
            <surname>Benchimol-Barbosa</surname>
            <given-names>Paulo Roberto</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2001">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nasario</surname>
            <given-names>Olivass&#233;</given-names>
            <suffix>Junior</suffix>
          </name>
          <xref ref-type="aff" rid="aff2001">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nadal</surname>
            <given-names>Jurandir</given-names>
          </name>
          <xref ref-type="aff" rid="aff2001">
            <sup>2</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1001">
        <label>1</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Hospital Universit&#225;rio Pedro Ernesto, Coordena&#231;&#227;o Cl&#237;nica, Rio de Janeiro, RJ &#8211; Brazil</institution>
      </aff>
      <aff id="aff2001">
        <label>2</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Universidade Federal do Rio de Janeiro, Instituto Alberto Luiz Coimbra de P&#243;s-Gradua&#231;&#227;o e Pesquisa de Engenharia, Rio de Janeiro, RJ &#8211; Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c01001">Mailing Address: Paulo Roberto Benchimol-Barbosa &#8226; Hospital Universit&#225;rio Pedro Ernesto &#8211; Boulevard Vinte e Oito de setembro, 77, Gabinete da Dire&#231;&#227;o Geral, T&#233;rreo. Postal Code 20551-030, Rio de Janeiro, RJ &#8211; Brazil E-mail: ecgar@yahoo.com, benchimol@globo.com</corresp>
        <fn fn-type="con">
          <p>Author contributions</p>
          <p>Conception and design of the research: Benchimol-Barbosa PR, Nasario-Junior O, Nadal J. Acquisition of data: Benchimol-Barbosa PR. Analysis and interpretation of the data: Benchimol-Barbosa PR, Nasario-Junior O, Nadal J. Statistical analysis: Benchimol-Barbosa PR, Nadal J. Obtaining financing: Nadal J. Writing of the manuscript: Benchimol-Barbosa PR, Nasario-Junior O, Nadal J. Critical revision of the manuscript for intellectual content: Benchimol-Barbosa PR, Nasario-Junior O, Nadal J.</p>
        </fn>
        <fn fn-type="conflict">
          <p>Potential Conflict of Interest</p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background</title>
          <p>Atrioventricular conduction time ( <italic>AVCT</italic> ) is influenced by autonomic input and subject to physiological remodeling.</p>
        </sec>
        <sec>
          <title>Objective</title>
          <p>To evaluate beat-by-beat <italic>AVCT</italic> and <italic>RR-interval</italic> variability in athletes and healthy sedentary subjects.</p>
        </sec>
        <sec>
          <title>Methods</title>
          <p>Twenty adults, including 10 healthy sedentary (Controls) and 10 elite long-distance runners (Athletes), age, weight and height-adjusted, underwent maximal metabolic equivalent (MET) assessment, and 15-min supine resting ECG recording seven days later. The interval between P-wave and R-wave peaks defined the <italic>AVCT</italic> . Mean (M) and standard deviation (SD) of consecutive <italic>RR-intervals (RR)</italic> and coupled <italic>AVCT</italic> were calculated, as well as regression lines of RR vs. <italic>AVCT (RR-AVCT)</italic> . Concordant AV conduction was defined as positive <italic>RR-AVCT slope</italic> and discordant otherwise. A multivariate linear regression model was developed to explain MET based on <italic>AVCT</italic> and <italic>RR-interval</italic> variability parameters. Significance-level: 5 %.</p>
        </sec>
        <sec>
          <title>Results</title>
          <p>In Athletes, <italic>M-RR</italic> and <italic>SD-RR</italic> values were higher than in Controls, whereas <italic>M-AVCT</italic> and <italic>SD-AVCT</italic> were not. <italic>RR-AVCT</italic> slopes were, respectively, 0.038 &#177; 0.022 and 0.0034 &#177; 0.017 (p &lt; 0.05). Using a cut-off value of 0.0044 (AUC 0.92 &#177; 0.07; p &lt; 0.001), <italic>RR-AVCT</italic> slope showed 100% specificity and 80% sensitivity. In a multivariate model, <italic>SD-RR</italic> and <italic>RR-AVCT</italic> slope were independent explanatory variables of MET (F-ratio: 17.2; p &lt; 0.001), showing 100% specificity and 90% sensitivity (AUC 0.99 &#177; 0.02; p &lt; 0.001).</p>
        </sec>
        <sec>
          <title>Conclusion</title>
          <p>In elite runners, <italic>AVCT</italic> to <italic>RR</italic> -interval dynamic coupling shows spontaneous discordant <italic>AV</italic> conduction, characterized by negative <italic>AVCT</italic> vs. <italic>RR</italic> -interval regression line slope. <italic>RR</italic> -intervals standard deviation and <italic>AVCT</italic> vs. <italic>RR</italic> -interval regression line slope are independent explanatory variables of MET (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Athletes</kwd>
        <kwd>Adults</kwd>
        <kwd>Resistance Training</kwd>
        <kwd>Physical Fitness</kwd>
        <kwd>Ventricular Remodeling</kwd>
        <kwd>Sedentarism</kwd>
        <kwd>Electrocardiography/methods</kwd>
        <kwd>Heart Ventricles</kwd>
        <kwd>Ventricular Function</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>Cardiac adaptation secondary to physical fitness is reflected in mechanical, electrical and autonomic remodeling of the heart, as a consequence of repeated high-demand activities. Well-trained athletes often have slight ventricular mass gain, increased ECG wave amplitude, early repolarization, reduction of resting heart rate and increased heart rate variability, related to the conditioning status.<sup><xref ref-type="bibr" rid="B1">1</xref> -7</sup></p>
        <p>Particularly, most autonomic heart remodeling in well-conditioned athletes is a consequence of increased vagal tonus and reduced sympathetic stimulation over the sinus and the atrioventricular (AV) nodes.<sup><xref ref-type="bibr" rid="B1">1</xref> , <xref ref-type="bibr" rid="B6">6</xref></sup> Although increased vagal tonus may be straightforwardly detected by measuring the resting heart rate, to differentiate between increased parasympathetic activity over the sinus node and the AV node on surface ECG may not be that simple.</p>
        <p>Frequently, high-demand athletes have atrioventricular (AV) node remodeling, characterized by several degrees of AV conduction block, non-sinus low atrial or junctional rhythm and, more rarely, complete AV block.<sup>8-10</sup>Those AV conduction disturbances depend on physical conditioning status and are related not only to increased parasympathetic activity over the AV node, but also to secondary remodeling of the AV node fibers and cell-to-cell coupling.<sup>11-13</sup></p>
        <p>Although <italic>AV</italic> conduction disturbances have been repeatedly documented in athletes, the dynamic <italic>AV</italic> conduction adaptation to the cardiac cycle in this population still needs clarification. In the general population, <italic>AV</italic> duration varies dynamically according to <italic>RR-interval</italic> duration, characterizing a concertina-like effect. However, in athletes, autonomic remodeling may influence dynamic <italic>AV</italic> conduction to <italic>RR-interval</italic> adaptation, leading to a distinct behavior of <italic>AV</italic> conduction, in a time-related response to <italic>RR-interval</italic> variation.</p>
        <p>The present study evaluated beat-by-beat <italic>AV</italic> conduction time ( <italic>AVCT</italic> ) and <italic>RR-interval</italic> variabilities in elite runners and healthy sedentary subjects, at rest, aiming at assessing the effect of physical fitness status on spontaneous <italic>AVCT</italic> to <italic>RR-interval</italic> duration coupling.</p>
      </sec>
      <sec sec-type="methods">
        <title>Methods</title>
        <p>Detailed information about study protocol, Ethics Committee approval, and ECG data acquisition has been described elsewhere.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> The present study analyzed raw high resolution ECG data from the ECG data bank of the Biomedical Engineering Program, using a novel technique for extraction of atrioventricular conduction time and <italic>RR-intervals</italic> .<sup>14</sup>Data sampling procedure was described elsewhere.<sup><xref ref-type="bibr" rid="B6">6</xref></sup></p>
        <p>The study population comprised 20 volunteers divided in two groups: the &#8216;Athlete&#8217; group, comprising ten elite long-distance runners (&#8805; 16.0 maximal metabolic equivalents [MET] calculated as the maximal oxygen consumption achieved during stress test divided by 3.5 ml&#183;kg<sup>-1</sup>&#183;min<sup>-1</sup>, [mean &#177; SD] 19.5 &#177; 1.3 MET; aged 25.1 &#177; 7.1 years), and the &#8216;Control&#8217; group, comprising ten male healthy sedentary volunteers (&#8804; 11.5 MET; 8.7 &#177; 1.9 MET; aged 29.0 &#177; 5.4 years). It is worth mentioning that the term &#8216;MET&#8217; is employed throughout the text as the maximal metabolic equivalent achieved during stress test. The athletes&#8217; training program consisted of six to eight training sessions/week; 90 to 120 min/session; 90 to 110 km/week. The waves and fiducial point detection were carried out on ECG acquired using <italic>XYZ</italic> modified <italic>Frank</italic> leads, in the resting supine position, using low-pass filter at 15 Hz ( <italic>Butterworth</italic> , 4th order). For the analysis of the <italic>RR-interval</italic> duration, artefacts and ectopic beats were adequately excluded.<sup>15,16</sup></p>
        <p>The distance between the peak of the <italic>P</italic> -wave and the peak of the <italic>R</italic> -wave in normal beats defined the <italic>PR-peak</italic> interval and was employed to analyze instantaneous <italic>AVCT</italic> adaptation over the cardiac cycle.<sup>14</sup>The <italic>PR-peak</italic> to <italic>RR-intervals</italic> coupling was assessed in a beat-by-beat basis throughout the whole ECG recording, using the lead showing the tallest <italic>P</italic> -wave, usually the <italic>Y</italic> lead. The <italic>RR-interval</italic> was assessed as the time between the peaks of the R-waves of two consecutive normal beats. The <italic>PR-peak</italic> interval was assessed immediately before the second beat of the respective <italic>RR-interval</italic> . For each subject, the mean <italic>(M)</italic> and standard deviation <italic>(SD)</italic> of all consecutive normal <italic>RR-intervals</italic> ( <italic>M-RR</italic> and <italic>SD-RR</italic> ) and respective <italic>PR-peak</italic> interval ( <italic>M-AVCT</italic> and SD- <italic>AVCT</italic> ) were calculated. <italic>PR-peak</italic> intervals were correlated to the respective <italic>RR-intervals</italic> and calculated regression line slopes ( <italic>RR-AVCT</italic> <sub>slope</sub>).</p>
        <sec>
          <title>Statistical Analysis</title>
          <p>The variables were expressed as mean &#177; SD or median and interquartile range, when appropriate. Data normality was assessed using Kolmogorov-Smirnov test, and all analyzed variables had their normality assumption accepted. Variables were compared between groups using non-paired Student&#8217;s t-test. To assess the optimal cut-off values, ROC curves were calculated from the regression line slopes ( <italic>AVCT</italic> vs. <italic>RR-</italic> interval) in both groups. A multivariate linear regression model was developed to explain the MET based on significant <italic>AVCT</italic> and <italic>RR-interval</italic> parameters. Pearson&#8217;s correlation coefficient r was tested for significance (significance level was set at 5%). A concordant AV conduction was arbitrarily defined as <italic>AVCT</italic> and <italic>RR-interval</italic> increased and decreased in the same direction in consecutive cardiac cycles, and discordant otherwise. <italic>AVCT</italic> was assessed as <italic>PR-peak-interval</italic> .</p>
          <p>A validation bootstrap resampling procedure applied to the multivariate model was carried out using two different approaches. In the first approach, 1100 replications with replacement were carried out in the whole sample of both groups to assess mean and SD estimates of independent variables. In a second approach, both groups were split in a test group, comprising 67% of subjects of each group, and a validation group, with the remaining 33%. The MET estimated by the multivariate model was employed to classify Controls and Athletes in all sets of bootstrap procedures. Raw ECG signals were processed using custom-made programs written in Matlab R2007a (The MathWorks, Inc) language. Statistical analysis was carried out using MS-Excel 360 (Microsoft Corporation) and Medcalc version 11 (Medcalc Software bvba). The significance level adopted in the statistical analysis was 5%.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Results</title>
        <p>The Athletes had significantly higher <italic>M-RR</italic> and <italic>SD-RR</italic> values than the Controls, whereas there were no significant differences between <italic>M-AVCT</italic> and <italic>SD-AVCT</italic> values ( <xref ref-type="table" rid="t1001">Table 1</xref> ). Examples of subjects from the Control (a) and Athlete (b) groups are shown in <xref ref-type="fig" rid="f01001">Figure 1</xref> , where regression lines and respective r of <italic>AVCT</italic> vs <italic>RR-intervals</italic> scatterplots are shown. <italic>RR-AVCT</italic> <sub>slope</sub>values are positive in Controls ( <xref ref-type="fig" rid="f01001">Figure 1-a</xref> ), whereas they are negative in Athletes ( <xref ref-type="fig" rid="f01001">Figure 1-b</xref> ). Overall, <italic>RR-AVCT</italic> <sub>slope</sub>in Controls and Athletes resulted in significant between-groups&#8217; differences ( <xref ref-type="table" rid="t1001">Table 1</xref> ).</p>
        <p>
          <table-wrap id="t1001">
            <label>Table 1</label>
            <caption>
              <title>&#8211; Univariate analyses of studied variables (mean &#177; SD)</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup width="17%">
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left" style="font-weight:normal"> </th>
                  <th style="font-weight:normal">
                    <italic>M-RR</italic>
                  </th>
                  <th style="font-weight:normal">
                    <italic>SD-RR</italic>
                  </th>
                  <th style="font-weight:normal">
                    <italic>M-AVCT</italic>
                  </th>
                  <th style="font-weight:normal">
                    <italic>SD-AVCT</italic>
                  </th>
                  <th style="font-weight:normal">
                    <italic>RR-AVCT<sub>slope</sub></italic>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>
                    <bold>Control group (mean &#177; SD)</bold>
                  </td>
                  <td align="center">853.9 &#177; 94.0</td>
                  <td align="center">44.5 &#177; 10.1</td>
                  <td align="center">134.0 &#177; 17.7</td>
                  <td align="center">2.8 &#177; 1.1</td>
                  <td align="center">0.0376 &#177; 0.0219</td>
                </tr>
                <tr>
                  <td>
                    <bold>Athlete group (mean &#177; SD)</bold>
                  </td>
                  <td align="center">1079.1 &#177; 207.9</td>
                  <td align="center">76.4 &#177; 21.0</td>
                  <td align="center">143.3 &#177; 27.6</td>
                  <td align="center">3.8 &#177; 2.2</td>
                  <td align="center">-0.0034 &#177; 0.0172</td>
                </tr>
                <tr>
                  <td>
                    <bold>p Significance level</bold>
                  </td>
                  <td align="center">0.0084</td>
                  <td align="center">0.0008</td>
                  <td align="center">0.3820</td>
                  <td align="center">0.2032</td>
                  <td align="center">0.002</td>
                </tr>
                <tr>
                  <td>
                    <bold>ROC statistics</bold>
                  </td>
                  <td> </td>
                  <td> </td>
                  <td> </td>
                  <td> </td>
                  <td> </td>
                </tr>
                <tr>
                  <td>Area under the ROC curve (AUC)</td>
                  <td align="center">0.89</td>
                  <td align="center">0.9</td>
                  <td align="center">0.56</td>
                  <td align="center">0.61</td>
                  <td align="center">0.92</td>
                </tr>
                <tr>
                  <td>Standard Error</td>
                  <td align="center">0.07</td>
                  <td align="center">0.08</td>
                  <td align="center">0.14</td>
                  <td align="center">0.14</td>
                  <td align="center">0.06</td>
                </tr>
                <tr>
                  <td>95% Confidence Interval</td>
                  <td align="center">0.67&#8211;0.98</td>
                  <td align="center">0.68&#8211;0.98</td>
                  <td align="center">0.32&#8211;0.78</td>
                  <td align="center">0.37&#8211;0.82</td>
                  <td align="center">0,71&#8211;0.99</td>
                </tr>
                <tr>
                  <td>z statistic</td>
                  <td align="center">5.5</td>
                  <td align="center">5.2</td>
                  <td align="center">0.4</td>
                  <td align="center">0.8</td>
                  <td align="center">6.7</td>
                </tr>
                <tr>
                  <td>p Significance level (area=0.5)</td>
                  <td align="center">&lt; 0.0001</td>
                  <td align="center">&lt; 0.0001</td>
                  <td align="center">0.6721</td>
                  <td align="center">0.4177</td>
                  <td align="center">&lt; 0.0001</td>
                </tr>
                <tr>
                  <td>Cut-off value</td>
                  <td align="center">917.3</td>
                  <td align="center">60.9</td>
                  <td align="center">124.1</td>
                  <td align="center">3.8</td>
                  <td align="center">0.0044</td>
                </tr>
                <tr>
                  <td>Specificity</td>
                  <td align="center">80 %</td>
                  <td align="center">100 %</td>
                  <td align="center">40 %</td>
                  <td align="center">50 %</td>
                  <td align="center">100 %</td>
                </tr>
                <tr>
                  <td>Sensitivity</td>
                  <td align="center">80 %</td>
                  <td align="center">80 %</td>
                  <td align="center">90 %</td>
                  <td align="center">80 %</td>
                  <td align="center">80 %</td>
                </tr>
                <tr>
                  <td>Accuracy</td>
                  <td align="center">80 %</td>
                  <td align="center">90 %</td>
                  <td align="center">65 %</td>
                  <td align="center">65 %</td>
                  <td align="center">90 %</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN1001">
                <p>
                  <italic>M-RR: mean of all normal RR-intervals; SD-RR: standard deviation of all normal RR-intervals; M-AVCT: mean of PR-peak intervals respective to normal RR-intervals; SD-AVCT: standard deviation of PR-peak intervals respective to normal RR-intervals; RR-AVCTslope: slope of the linear regression line between PR-peak intervals and respective RR interval</italic>
                </p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </p>
        <p>
          <fig id="f01001">
            <label>Figure 1</label>
            <caption>
              <title>&#8211; <italic>Scatterplot and regression line of beat-by-beat RR-interval as a function of respective PR-peak interval of a 30 y.o. Control subject (a) and a 19 y.o. Athlete (b). Two hundred heartbeat sequences of respective RR- and PR-peak intervals series are shown in (c) and (d). In (a), PR-peak interval increases as RR interval increases (positive slope: 0.0227; r = 0.50; p &lt; 0.01), clearly observed in (c) (spontaneous concordant condition). Conversely, in (b), PR-peak interval decreases as RR interval increases (negative slope: -0.0316; r = -0.68; p &lt; 0.01). In (d), note periods of reciprocal variation in RR- and PR-peak intervals (spontaneous discordant conduction): PR-peak interval shortens as RR-interval increases (dotted arrow) and PR-peak interval increases as RR-interval shortens (decremental conduction, solid arrow) (see text for details).</italic></title>
            </caption>
            <graphic xlink:href="1678-4170-abc-115-01-0071-90281-gf01-en.tif"/></fig>
        </p>
        <p>Variables showing significant intergroup differences were entered into a multivariate linear regression model, taking MET as the dependent variable in the bootstrap procedure. <italic>SD-RR</italic> (p = 0.0099) and RR- <italic>AVCT</italic> <sub>slope</sub>(p = 0.006) were independent explanatory variables of MET, showing 90% specificity, 100% sensitivity and 95% total accuracy ( <xref ref-type="table" rid="t2001">Table 2</xref> ). The average C-statistic in test and validation groups were, respectively, 0.97 &#177; 0.06 and 0.87 &#177; 0.13; p &lt; 0.001 for both. The multivariate linear regression analysis and respective bootstrap procedures results are summarized in <xref ref-type="table" rid="t2001">Table 2</xref> .</p>
        <p>
          <table-wrap id="t2001">
            <label>Table 2</label>
            <caption>
              <title>&#8211; Multivariable explanatory model of the maximal VO2 consumption; 1100 bootstrap resampling procedure results and Internal validation of the maximal VO2 consumption multivariable explanatory model using bootstrap 2:1 &#8216;Test&#8217; vs &#8216;Validation&#8217; procedure results</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup width="14%">
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left" style="font-weight:normal"> </th>
                  <th colspan="2" style="font-weight:normal">Multivariate model</th>
                  <th colspan="2" style="font-weight:normal">Bootstrap procedure</th>
                  <th colspan="2" style="font-weight:normal">Bootstrap test-validation</th>
                </tr>
                <tr>
                  <th align="left" colspan="7" style="font-weight:normal">
                    <hr/>
                  </th>
                </tr>
                <tr>
                  <th align="left" style="font-weight:normal">Model Variables</th>
                  <th style="font-weight:normal">Coefficients &#177;</th>
                  <th style="font-weight:normal">
                    <italic>p</italic>
                  </th>
                  <th style="font-weight:normal">Coefficients &#177;</th>
                  <th style="font-weight:normal">
                    <italic>p</italic>
                  </th>
                  <th style="font-weight:normal">Coefficients &#177;</th>
                  <th style="font-weight:normal">
                    <italic>p</italic>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>
                    <bold>PR to RR slope (15 Hz)</bold>
                  </td>
                  <td align="center">-100.36 &#177; 31.97</td>
                  <td align="center">0.006</td>
                  <td align="center">-105.76 &#177; 33.93</td>
                  <td align="center">0.0009</td>
                  <td align="center">-101.42 &#177; 29.39</td>
                  <td align="center">0.0003</td>
                </tr>
                <tr>
                  <td>
                    <bold>
                      <italic>SD RR</italic>
                    </bold>
                  </td>
                  <td align="center">0.115 &#177; 0.040</td>
                  <td align="center">0.0099</td>
                  <td align="center">0.115 &#177; 0.041</td>
                  <td align="center">0.003</td>
                  <td align="center">0.115 &#177; 0.036</td>
                  <td align="center">0.0007</td>
                </tr>
                <tr>
                  <td>
                    <bold>
                      <italic>Constant</italic>
                    </bold>
                  </td>
                  <td align="center">8.88</td>
                  <td align="center"> </td>
                  <td align="center">8.75 &#177; 3.22</td>
                  <td align="center">0.003</td>
                  <td align="center">8.85 &#177; 2.83</td>
                  <td align="center">0.0009</td>
                </tr>
                <tr>
                  <td>ROC statistics</td>
                  <td> </td>
                  <td> </td>
                  <td> </td>
                  <td> </td>
                  <td align="center">Test group</td>
                  <td align="center">Validation group</td>
                </tr>
                <tr>
                  <td>Area under the ROC curve (AUC)</td>
                  <td align="center">0.99</td>
                  <td> </td>
                  <td align="center">0.99</td>
                  <td> </td>
                  <td align="center">0.97</td>
                  <td align="center">0.87</td>
                </tr>
                <tr>
                  <td>Standard Error</td>
                  <td align="center">0.02</td>
                  <td> </td>
                  <td align="center">0.02</td>
                  <td> </td>
                  <td align="center">0.06</td>
                  <td align="center">0.13</td>
                </tr>
                <tr>
                  <td>95% Confidence Interval</td>
                  <td align="center">0.94&#8211;1.00</td>
                  <td> </td>
                  <td align="center">0.94&#8211;1.00</td>
                  <td> </td>
                  <td align="center">0.85&#8211;1.00</td>
                  <td align="center">0.61&#8211;1.00</td>
                </tr>
                <tr>
                  <td>z statistic</td>
                  <td align="center">42.1</td>
                  <td> </td>
                  <td align="center">42.1</td>
                  <td> </td>
                  <td align="center">16.7</td>
                  <td align="center">6.5</td>
                </tr>
                <tr>
                  <td><italic>p</italic> Significance level (area=0.5)</td>
                  <td align="center">&lt; 0.001</td>
                  <td> </td>
                  <td align="center">&lt; 0.001</td>
                  <td> </td>
                  <td align="center">&lt; 0.001</td>
                  <td align="center">&lt; 0.001</td>
                </tr>
                <tr>
                  <td>Cut-off value</td>
                  <td align="center">12.3</td>
                  <td> </td>
                  <td align="center">12.0</td>
                  <td> </td>
                  <td align="center">14.2</td>
                  <td> </td>
                </tr>
                <tr>
                  <td>Specificity</td>
                  <td align="center">90%</td>
                  <td> </td>
                  <td align="center">90%</td>
                  <td> </td>
                  <td align="center">90.2%</td>
                  <td align="center">81.0%</td>
                </tr>
                <tr>
                  <td>Sensitivity</td>
                  <td align="center">100%</td>
                  <td> </td>
                  <td align="center">100%</td>
                  <td> </td>
                  <td align="center">96.7%</td>
                  <td align="center">80.4%</td>
                </tr>
                <tr>
                  <td>Total accuracy</td>
                  <td align="center">95%</td>
                  <td> </td>
                  <td align="center">95%</td>
                  <td> </td>
                  <td align="center">93.4%</td>
                  <td align="center">80.7%</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN2001">
                <p>
                  <italic>* Procedimento de bootstrap realizado sem restitui&#231;&#227;o. O modelo explicativo multivariado foi calculado no grupo Teste e validado no grupo Valida&#231;&#227;o; &#177; = (m&#233;dia &#177; DP).</italic>
                </p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </p>
        <p>The RR- <italic>AVCT</italic> <sub>slope</sub>values for each group, including interquartile range and 95% confidence intervals (CI) are shown in <xref ref-type="fig" rid="f02001">figure 2-a</xref> . Sensitivity, specificity and total accuracy were computed utilizing the optimal cutoff value shown in <xref ref-type="table" rid="t1001">table 1</xref> , and exhibited as inset. To highlight the association between spontaneous decremental conduction and physical status, a regression line of RR- <italic>AVCT</italic> <sub>slope</sub>vs. MET is shown in <xref ref-type="fig" rid="f02001">figure 2-a</xref> . It shows a significant correlation (r = 0.70; p &lt; 0.05) and a negative slope, demonstrating that RR- <italic>AVCT</italic> <sub>slope</sub>decreases as MET increases. An example of a short sequence of sinus beats showing spontaneous decremental conduction, registered during supine rest in a 19 y.o. athlete (MET 16.8 METs) is shown in <xref ref-type="fig" rid="f02001">Figure 2-b</xref> .</p>
        <p>
          <fig id="f02001">
            <label>Figure 2</label>
            <caption>
              <title>&#8211; <italic>(a) Regression line slope values of pooled AVCT vs. mean RR-intervals (RR-AVCTslope) as a function of VO2 consumption expressed as maximal metabolic equivalent (MET) achieved during stress test and respective boxplot. Note that RR-AVCTslope tends to be more negative as physical conditioning status increases (grey dots), when compared to sedentary individuals (white dots). Box-plots showing median, interquartile range and 95% confidence intervals are shown in the vicinity of the respective group points. Specificity, sensitivity and accuracy values were computed utilizing RR-AVCTslope = 0.0044 as a cut-off criterion. (b) Illustration of 19 y.o. Athlete&#8217;s ECG segment depicting a sequence of normal sinus beats showing AVCT lengthening as RR-interval decreases, indicating AV decremental conduction. Note P-wave and R wave peaks taken as the fiducial points for assessment of the PR-peak interval. AVCT was assessed as PR peak interval. AVCT &#8211; atrioventricular conduction time (see text for details).</italic></title>
            </caption>
            <graphic xlink:href="1678-4170-abc-115-01-0071-90281-gf02-en.tif"/></fig>
        </p>
      </sec>
      <sec sec-type="discussion">
        <title>Discussion</title>
        <p>Atrial ventricular conduction is the most important determinant of the <italic>PR-interval</italic> duration, which undergoes dynamic fluctuations depending on autonomic and health statuses, age, instantaneous HR, medications, stance and respiratory frequency.<sup>17</sup>The evaluation of the <italic>PR-interval</italic> by using either <italic>P</italic> wave-onset or <italic>P</italic> wave-peak approaches as fiducial points has been shown to provide accurate and precise results, and, thus, are both appropriate to assess <italic>AVCT</italic> inter-beat variations.<sup>14,17</sup></p>
        <p>In the present study, highly trained longdistance runners and healthy sedentary subjects had their maximal aerobic power assessed, and <italic>AVCT</italic> coupled to the preceding <italic>RR-interval</italic> variability, assessed on resting supine ECG. It was hypothesized that, at rest, AV conduction would be affected by AV remodeling induced by high-end training, causing <italic>AVCT</italic> to <italic>RR-interval</italic> coupling to behave differently from sedentary conditions. In a linear model, <italic>AVCT</italic> to <italic>RR-interval</italic> coupling showed an average negative regression line slope in the Athlete group and, conversely, an average positive slope in the Control group, indicating that AV node remodeling due to training induces decremental conduction enhancement. A potentially distinguished measure of physical fitness, <italic>AVCT</italic> to <italic>RR-interval</italic> regression slope correctly identified 90% all subjects&#8217; related physical fitness status. Although identification of decremental conduction in athletes is a common finding, the application of a linear modeling to quantify <italic>AVCT</italic> and its relation to <italic>RR-interval</italic> in highly trained athletes has not been yet reported, to the best of our knowledge.</p>
        <p>Previous studies evidenced a high prevalence of Mobitz I 2nd degree AV block in long distance runners at rest.<sup>8-10</sup>In the present study, the occurrence of spontaneous <italic>PR-peak-interval</italic> lengthening related to <italic>RR-interval</italic> shortening was a major finding, making the average slope negative in the Athletes group ( <xref ref-type="fig" rid="f02001">Figure 2b</xref> ). Conversely to these studies, no blocked <italic>P</italic> -wave was found after a carefully revision of signals. Spontaneous episodes of decremental conduction were frequent in the Athletes group (57.9% of aggregated ECG recording time of Athletes) and rare in the Control group (7.9% of aggregated ECG time recording of Controls). Furthermore, when the <italic>AVCT</italic> vs. <italic>RR-interval</italic> regression slope was plotted against MET, it was observed that the higher the MET, the more negative the RR- <italic>AVCT</italic> <sub>slope</sub>, showing that spontaneous decremental AV conduction becomes more frequent as physical conditioning status improves ( <xref ref-type="fig" rid="f02001">Figure 2a</xref> ). Noteworthy was that the decremental conduction was more frequently observed when <italic>RR-interval</italic> was larger than 1022.0 ms. <italic>PR-peak</italic> interval reduction related to RR interval increase was also observed in Athletes ( <xref ref-type="fig" rid="f01001">Figure 1d</xref> ). A possible explanation for this latter finding is the common occurrence of vagal-induced spontaneous para-sinus pacing activity.</p>
        <p>It has been shown that the resting ECG of endurance athletes may show distinctive features from demographically equivalent healthy sedentary subjects, bearing similarities to those observed in elderly individuals and/or patients with cardiovascular disease.<sup>18</sup>However, in athletes, AV conduction abnormalities have been related to higher parasympathetic activity, differently from the elderly.19 Contemporary studies have shown that athletic training could induce intrinsic physiological adaptations in the conduction system, contributing to the higher prevalence of AV conduction abnormalities.<sup>11-13</sup>The physiological mechanisms by which endurance training induces those intrinsic changes in the cardiac conduction system are limitedly understood and may be multifactorial, but anatomic changes such as atrial and ventricular dilation has been shown to create a mechanical-to-electrical remodeling necessary to cause intrinsic AV electrophysiological adaptations.<sup>7,11</sup></p>
        <p>Limitations of the present study include the sample size of two distinct groups regarding the physical conditioning status. Raw ECG signals were obtained from the ECG database available in the Biomedical Engineering Program (convenience sample). <italic>Peak-P</italic> to <italic>Peak-R</italic> interval was employed as a surrogate of conventional <italic>PR-interval</italic> measurement. Although it has been shown that <italic>Peak-P</italic> to <italic>Peak-R</italic> interval appropriately describes <italic>PR-interval</italic> dynamicity, the duration of the actual <italic>PR-interval</italic> may be larger than the one observed in the present study. It was observed that both <italic>M-AVCT</italic> and <italic>SD-AVCT</italic> were larger among athletes when compared to controls, although statistical significance was not reached. The explanation of this finding may be twofold: i) although <italic>AVCT</italic> variability was expected to be higher among athletes, no true Mobitz I block was in fact observed after careful signal revision. This indicates that <italic>AVCT</italic> variability was expected to be increased to a limited extent, and ii) the sample size of the present sample was designed to determine differences related to ventricular activation total energy<sup><xref ref-type="bibr" rid="B6">6</xref></sup> , thus limiting its statistical power to detect <italic>AVCT</italic> variation between groups. Subjects were kept on supine rest for 10 minutes before ECG acquisition, aiming at preventing orthostatic memory effect on AV conduction to influence AV conduction to <italic>RR-interval</italic> coupling dynamicity, in a controlled temperature and acoustically isolated environment. However, it cannot be completely ruled out that some orthostatic memory effect might still be present. In this study, we observed the occurrence of spontaneous <italic>PR-peak</italic> interval enlargement as <italic>RR-interval</italic> decreased, and vice-versa. This phenomenon was interpreted as a manifestation of decremental conduction during the transit of the cardiac activation wave-front through the AV node. However, due to the nature of this study, no invasive electrophysiological test was carried out to further characterize decremental conduction or para-sinus pacing activity. It is still necessary to investigate the potential impact of the present findings on clinical settings, such as a marker for supraventricular tachyarrhythmia, particularly AV nodal reentrant arrhythmia and atrial fibrillation.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclusion</title>
        <p>The atrioventricular node undergoes substantial physiological remodeling in elite long-distance runners, characterized by spontaneous AV decremental conduction at supine rest, rarely observed in healthy sedentary subjects under the same resting conditions. The linear regression line slope of <italic>PR-peak</italic> to <italic>RR-interval</italic> coupling is a strong and independent explanatory variable of maximal metabolic equivalent achieved during stress test in this population.</p>
      </sec>
    </body>
    <back>
      <ack>
        <title>Acknowledgement</title>
        <p>We wish to thank Dr. Moacir Marocolo who recruited the study subjects and acquired ECG signals, contributing to the ECG database of the Biomedical Engineering Program. The ECG signals acquisition was carried out with the participation and under the personal guidance of Dr. Paulo Roberto Benchimol-Barbosa.</p>
      </ack>
      <fn-group>
        <fn fn-type="other">
          <p>Study Association</p>
          <p>This study is not associated with any thesis or dissertation work.</p>
        </fn>
        <fn fn-type="other">
          <p>Ethics approval and consent to participate</p>
          <p>This study was approved by the Ethics Committee of the Instituto Nacional de Cardiologia under the protocol number 0026/20.02.04. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Errata</bold>
          </p>
          <p>Ahead of Print</p>
          <p>In the original article published in ahead of print with the title &#8220;Avalia&#231;&#227;o do Tempo de Condu&#231;&#227;o Atrioventricular Din&#226;mica para Acoplamento ao Intervalo RR em Atletas e Indiv&#237;duos Sedent&#225;rios&#8221;, with DOI number: https://doi.org/10.36660/abc.20190281, published in the periodical Arquivos Brasileiros de Cardiologia, consider the title correct: &#8220;Avalia&#231;&#227;o da Din&#226;mica do Acoplamento da Condu&#231;&#227;o Atrioventricular &#224; Varia&#231;&#227;o dos Intervalos RR em Atletas e Indiv&#237;duos Sedent&#225;rios&#8221;.</p>
        </fn>
      </fn-group>
      <fn-group>
        <fn fn-type="supported-by">
          <p>Sources of Funding</p>
          <p>This study was funded by FINEP, CNPq and CAPES.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
