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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="case-report" 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">3XVQdc8JhZrLCbRfyQKWqKG</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2020001000010</article-id>
      <article-id pub-id-type="publisher-id">abc.20190363</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20190363</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Relato de Caso</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Bloqueio do Ramo Esquerdo Idiop&#225;tico e Sintomas Inexplic&#225;veis Durante o Exerc&#237;cio: Um Relato de Caso</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-2304-3110</contrib-id>
          <name>
            <surname>Guimar&#227;es</surname>
            <given-names>Guilherme Veiga</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Bocchi</surname>
            <given-names>Edimar Alcides</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
        <institution content-type="orgdiv1">Instituto do Cora&#231;&#227;o</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Universidade de S&#227;o Paulo Instituto do Cora&#231;&#227;o,S&#227;o Paulo, SP &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c01"> Correspond&#234;ncia: Guilherme Veiga Guimar&#227;es &#8226; Universidade de S&#227;o Paulo Instituto do Cora&#231;&#227;o &#8211; Av. Dr. Eneas de Carvalho Aguiar, 44. CEP 05403-000, S&#227;o Paulo, SP &#8211; Brasil E-mail: <email>gvguima@usp.br</email> </corresp>
        <fn fn-type="con">
          <p>Contribui&#231;&#227;o dos Autores</p>
          <p>Concep&#231;&#227;o e desenho da pesquisa, Obten&#231;&#227;o de dados e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Guimar&#227;es GV; An&#225;lise e interpreta&#231;&#227;o dos dados e Reda&#231;&#227;o do manuscrito: Guimar&#227;es GV, Bocchi EA.</p>
        </fn>
        <fn fn-type="conflict">
          <p>Potencial Conflito de Interesses</p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>14</day>
        <month>09</month>
        <year>2020</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>04</month>
        <year>2020</year>
      </pub-date>
      <volume>115</volume>
      <issue>1 suppl 1</issue>
      <fpage>10</fpage>
      <lpage>13</lpage>
      <history>
        <date date-type="received">
          <day>05</day>
          <month>06</month>
          <year>2019</year>
        </date>
        <date date-type="rev-recd">
          <day>25</day>
          <month>07</month>
          <year>2019</year>
        </date>
        <date date-type="accepted">
          <day>10</day>
          <month>09</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>
      <kwd-group xml:lang="pt">
        <kwd>Bloqueio de Ramo</kwd>
        <kwd>Exerc&#237;cio</kwd>
        <kwd>Atividade F&#237;sica</kwd>
        <kwd>Consumo de Oxig&#234;nio/fisiologia</kwd>
        <kwd>Doen&#231;as Cardiovasculares/preven&#231;&#227;o e controle</kwd>
      </kwd-group>
      <funding-group>
        <award-group>
          <funding-source>Conselho Nacional de Desenvolvimento Cient&#237;fico e Tecnol&#243;gico</funding-source>
          <award-id>301957/2017-7</award-id>
        </award-group>
        <funding-statement>Fontes de Financiamento</funding-statement>
      </funding-group>
      <counts>
        <fig-count count="4"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="11"/>
        <page-count count="4"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>A presen&#231;a de bloqueio do ramo esquerdo (BRE) na aparente aus&#234;ncia de outra doen&#231;a card&#237;aca suscita quest&#245;es e preocupa&#231;&#245;es a respeito da estratifica&#231;&#227;o de risco de eventos ou sintomas cardiovasculares subsequentes.<sup><xref ref-type="bibr" rid="B1">1</xref> - <xref ref-type="bibr" rid="B5">5</xref></sup> Estima-se que a detec&#231;&#227;o de BRE em adultos assintom&#225;ticos, inclusive em atletas, varie entre 0,1% e 0,8%, o que muito provavelmente corresponde a doen&#231;as card&#237;acas estruturais, e n&#227;o a respostas fisiol&#243;gicas ao exerc&#237;cio.<sup><xref ref-type="bibr" rid="B6">6</xref> - <xref ref-type="bibr" rid="B8">8</xref></sup> Por outro lado, alguns estudos demonstraram que o risco de morte dos pacientes com BRE e doen&#231;a card&#237;aca varia entre 2,4% e 11% ao ano.<sup><xref ref-type="bibr" rid="B9">9</xref></sup></p>
      <p>Embora v&#225;rios estudos tenham sugerido que o BRE induzido por exerc&#237;cio esteja geralmente associado &#224; doen&#231;a cardiovascular, sobretudo &#224; doen&#231;a arterial coronariana, h&#225; estudos contrastantes que demonstram uma rela&#231;&#227;o entre o BRE induzido por exerc&#237;cio e art&#233;rias coron&#225;rias normais.<sup><xref ref-type="bibr" rid="B6">6</xref> , <xref ref-type="bibr" rid="B7">7</xref> , <xref ref-type="bibr" rid="B9">9</xref></sup> Entretanto, os efeitos cardiovasculares adversos relacionados ao exerc&#237;cio no BRE com fun&#231;&#227;o card&#237;aca normal em repouso ainda s&#227;o pouco definidos.</p>
      <p>Este relato de caso examinou a rela&#231;&#227;o entre o exerc&#237;cio, o BRE, sintomas e capacidade de exerc&#237;cio em mulher mais jovem com BRE t&#237;pico, sem hist&#243;ria de doen&#231;a cardiovascular, que relatou ansiedade e falta de ar s&#250;bitas durante exerc&#237;cio vigoroso, o que pode ser sugestivo de doen&#231;a card&#237;aca, tendo sido encaminhada para teste de esfor&#231;o.</p>
    </sec>
    <sec>
      <title>Relato de Caso</title>
      <p>Mulher saud&#225;vel de 42 anos de idade com BRE, que relatou ansiedade e falta de ar s&#250;bitas durante exerc&#237;cio vigoroso, encaminhada para teste cardiopulmonar do exerc&#237;cio (TCPE) para avalia&#231;&#227;o dos sintomas inexplic&#225;veis. Ela n&#227;o estava tomando nenhuma medica&#231;&#227;o e n&#227;o tinha hist&#243;rico m&#233;dico relevante. Sem sintomas pr&#233;vios sugestivos de doen&#231;a card&#237;aca (desconforto no peito, palpita&#231;&#245;es, desmaios e angina). N&#227;o havia hist&#243;ria de doen&#231;a neuromuscular ou pulmonar. Ela n&#227;o fumava nem consumia &#225;lcool. N&#227;o havia hist&#243;ria familiar de doen&#231;a card&#237;aca ou ataque card&#237;aco. Nos seis meses anteriores, ela vinha se exercitando tr&#234;s vezes por semana em uma academia. O programa de exerc&#237;cio consistia em sess&#245;es de pelo menos 60 minutos de atividade regular de intensidade moderada, incluindo exerc&#237;cios aer&#243;bicos, de fortalecimento e flexibilidade muscular e de fortalecimento do equil&#237;brio. Seu exame f&#237;sico foi considerado normal, o IMC era 21,5 kg/m<sup>2</sup> e a press&#227;o arterial em repouso estava em 110/70 mmHg. O eletrocardiograma (ECG) em repouso mostrou ritmo sinusal (RS) e frequ&#234;ncia card&#237;aca (FC) de 70 bpm, com caracter&#237;stica dominante de bloqueio intraventricular: complexo QRS prolongado (&#8805;0,12s) resultante do atraso na ativa&#231;&#227;o do ventr&#237;culo esquerdo, acompanhado de morfologia caracter&#237;stica do complexo QRS.6 A angiotomografia coronariana (ATC) foi realizada, e n&#227;o mostrou dep&#243;sitos de c&#225;lcio e gordura nas art&#233;rias coron&#225;rias, nem art&#233;rias coron&#225;rias com estenose. O hemograma completo mostrou resultados normais: glicemia de jejum: 78 mg/dL; colesterol lipoprote&#237;na de baixa densidade (LDL): 168 mg/dL; colesterol lipoprote&#237;na de alta densidade (HDL): 81 mg/dL; colesterol total (CT): 159 mg/dL; lipoprote&#237;na (a) [Lp(a)]: 7 mg/dL; triglic&#233;rides (Tg): 49 mg/dL e creatina fosfoquinase (CPK): 26 U/L. A resson&#226;ncia magn&#233;tica (RM) do cora&#231;&#227;o mostrou fun&#231;&#227;o biventricular normal, fra&#231;&#227;o de eje&#231;&#227;o do VE de 65% e dimens&#245;es preservadas, exceto por um movimento septal anormal.</p>
      <p>Foi submetida ao TCPE em uma esteira. Ao longo do TCPE, o ECG de 12 deriva&#231;&#245;es mostrou ritmo sinusal ( <xref ref-type="fig" rid="f01">Figura 1</xref> ). As aferi&#231;&#245;es da press&#227;o arterial estavam dentro da normalidade: em repouso (126/82 mmHg), pico (160/90 mmHg) e recupera&#231;&#227;o (120/90 mmHg). Ela parou o exerc&#237;cio por causa da fadiga (RER=1,29). Os valores de pico de consumo de oxig&#234;nio (VO<sub>2</sub>, pico = 27,1 ml/kg/min) e frequ&#234;ncia card&#237;aca m&#225;xima (FCM = 176 bpm) obtidos no TCPE foram normais para a idade e o sexo: 95% e 102%, respectivamente (https://www.ahajournals.org/doi/10.1161/01.CIR.91.2.580). Do est&#225;gio 14 do protocolo de Balke modificado at&#233; o final do teste, o TCPE identificou uma redu&#231;&#227;o do VO<sub>2</sub> e do pulso O<sub>2</sub> (VO<sub>2</sub>/FC, ml/bpm), e um aumento da FC e da rela&#231;&#227;o espa&#231;o morto/volume corrente (Vd/Vt) ( <xref ref-type="fig" rid="f02">Figura 2</xref> ). A partir deste evento, a inclina&#231;&#227;o da rela&#231;&#227;o entre ventila&#231;&#227;o minuto/produ&#231;&#227;o de di&#243;xido de carbono (VE/VCO<sub>2</sub>) aumentou abruptamente e n&#227;o foi acompanhada de hip&#243;xia ( <xref ref-type="fig" rid="f02">Figura 2</xref> ).</p>
      <p>
        <fig id="f01">
          <label>Figura 1</label>
          <caption>
            <title>&#8211; Teste cardiopulmonar do exerc&#237;cio em repouso, durante o exerc&#237;cio e a recupera&#231;&#227;o. As linhas pretas indicam a transi&#231;&#227;o entre essas fases. A) linha verde &#8211; consumo de oxig&#234;nio (VO2/kg, ml/kg/min), linha vermelha &#8211; frequ&#234;ncia card&#237;aca (FC, bpm), linha preta &#8211; pulso de oxig&#234;nio (O2-Pls, ml/bpm) e linha azul &#8211; quociente respirat&#243;rio (QR); B) linha verde &#8211; ventila&#231;&#227;o por minuto (VE, l/min), linha vermelha &#8211; taxa respirat&#243;ria (RR), linha preta &#8211; volume corrente (Vt, ml/min) e linha azul - raz&#227;o espa&#231;o morto/volume corrente (Vd/Vt). C) Inclina&#231;&#227;o da rela&#231;&#227;o entre ventila&#231;&#227;o minuto/produ&#231;&#227;o de di&#243;xido de carbono (VE/VCO2). Na primeira parte do exerc&#237;cio, a inclina&#231;&#227;o VE/VCO2 est&#225; normal (21); a partir do momento do evento, durante o teste de esfor&#231;o, a inclina&#231;&#227;o VE/VCO2 aumentou vertiginosamente (49). Seta marrom &#8211; momento do evento.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-115-1suppl1-0010-90363-gf01.tif"/></fig>
      </p>
      <p>
        <fig id="f02">
          <label>Figura 2</label>
          <caption>
            <title>&#8211; Eletrocardiograma demonstrando bloqueio de ramo esquerdo: taxa de repouso de 75 bpm (A), frequ&#234;ncia card&#237;aca de 175 bpm durante o teste de toler&#226;ncia ao exerc&#237;cio m&#225;ximo (B) e frequ&#234;ncia card&#237;aca de 153 bpm no primeiro minuto do per&#237;odo de recupera&#231;&#227;o (C).</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-115-1suppl1-0010-90363-gf02.tif"/></fig>
      </p>
    </sec>
    <sec sec-type="discussion">
      <title>Discuss&#227;o</title>
      <p>Tanto quanto &#233; do nosso conhecimento, relatamos pela primeira vez o caso de uma paciente mais jovem com BRE sem cardiomiopatia aparente e com sintomas inexplic&#225;veis durante exerc&#237;cio vigoroso (redu&#231;&#227;o no VO<sub>2</sub> durante o TCPE), o que &#233; sugestivo de fun&#231;&#227;o card&#237;aca comprometida como consequ&#234;ncia de estresse cardiovascular. O ECG n&#227;o revelou anomalias, a n&#227;o ser pelo BRE. A reserva de frequ&#234;ncia card&#237;aca e a press&#227;o arterial permaneceram normais ao longo do TCPE.</p>
      <p>O exerc&#237;cio oferece uma ferramenta &#250;til para a avaliar indiretamente a reserva funcional card&#237;aca, a partir do desempenho ventricular esquerdo, as altera&#231;&#245;es do repouso para o pico do esfor&#231;o, podendo ser limitado na presen&#231;a de doen&#231;as. Nesse contexto, uma queda no padr&#227;o cardiovascular de resposta do VO<sub>2</sub> pode indicar um comprometimento do d&#233;bito card&#237;aco (DC) ou da extra&#231;&#227;o perif&#233;rica de oxig&#234;nio, conforme observado na insufici&#234;ncia card&#237;aca.10 Por outro lado, nos indiv&#237;duos saud&#225;veis, o n&#237;vel de aumento do consumo e extra&#231;&#227;o perif&#233;rica de oxig&#234;nio em resposta ao exerc&#237;cio &#233; muito maior, quando comparado com as altera&#231;&#245;es no volume sist&#243;lico, e semelhante ao aumento observado na FC.</p>
      <p>A redu&#231;&#227;o do VO<sub>2</sub> e do pulso O<sub>2</sub>, apesar do aumento na FC, observada nesse caso, pode indicar uma poss&#237;vel anomalia card&#237;aca. Sugerimos que o movimento ass&#237;ncrono do ventr&#237;culo esquerdo, com o atraso da contra&#231;&#227;o de suas paredes, pode diminuir a carga de trabalho do ventr&#237;culo esquerdo, resultando em um volume sist&#243;lico mais baixo e indicando uma diminui&#231;&#227;o do d&#233;bito card&#237;aco durante o exerc&#237;cio m&#225;ximo, apesar do aumento na FC.<sup><xref ref-type="bibr" rid="B8">8</xref> - <xref ref-type="bibr" rid="B10">10</xref></sup> Essa redu&#231;&#227;o na carga de trabalho do ventr&#237;culo esquerdo por um aparente defeito de perfus&#227;o septal durante o TCPE pode ocasionar perda de energia e &#8220;desperd&#237;cio&#8221; de trabalho mioc&#225;rdico, o que pode representar o impacto hemodin&#226;mico da ativa&#231;&#227;o el&#233;trica ass&#237;ncrona do mioc&#225;rdio no BRE,<sup><xref ref-type="bibr" rid="B8">8</xref> - <xref ref-type="bibr" rid="B10">10</xref></sup> al&#233;m de explicar, em parte, a queda do VO<sub>2</sub> observada durante o TCPE. Por outro lado, o bloqueio do ramo esquerdo induzido por exerc&#237;cio pode estar relacionado ou n&#227;o a altera&#231;&#245;es card&#237;acas aparentes. Entretanto, os pacientes com este achado apresentaram taxas de mortalidade por todas as causas significativamente maiores se comparados &#224;queles sem bloqueio do ramo esquerdo induzido por exerc&#237;cio.<sup><xref ref-type="bibr" rid="B11">11</xref></sup></p>
      <p>Essa aparente diminui&#231;&#227;o da fun&#231;&#227;o card&#237;aca durante o exerc&#237;cio pode ser decorrente de uma diminui&#231;&#227;o transit&#243;ria do volume sist&#243;lico, provavelmente relacionada a uma piora da fun&#231;&#227;o ventricular esquerda (VE), associada a um aumento repentino da inclina&#231;&#227;o VE/VCO<sub>2</sub>, dando origem a uma maior raz&#227;o entre o espa&#231;o morto e o volume corrente (Vd/Vt) e a um aumento precoce da frequ&#234;ncia respirat&#243;ria, como mecanismos compensat&#243;rios.<sup><xref ref-type="bibr" rid="B1">1</xref> , <xref ref-type="bibr" rid="B3">3</xref> , <xref ref-type="bibr" rid="B5">5</xref> , <xref ref-type="bibr" rid="B10">10</xref></sup> Esse dist&#250;rbio na fisiopatologia est&#225; relacionado com a disfun&#231;&#227;o do VE, provocada ou piorada pelo BRE, o que pode ocasionar indiretamente uma disfun&#231;&#227;o ventricular direita, por meio do aumento da press&#227;o de enchimento do lado esquerdo, causando altera&#231;&#245;es na fun&#231;&#227;o das vias a&#233;reas dos pulm&#245;es, e o surgimento de troca anormal de gases em decorr&#234;ncia da disfun&#231;&#227;o alv&#233;olo-capilar.<sup><xref ref-type="bibr" rid="B3">3</xref> , <xref ref-type="bibr" rid="B4">4</xref></sup> Al&#233;m disso, uma inclina&#231;&#227;o VE/VCO<sub>2</sub> mais elevada &#233; indicativa de hipertens&#227;o pulmonar secund&#225;ria, como consequ&#234;ncia de outras condi&#231;&#245;es prim&#225;rias, tais como insufici&#234;ncia card&#237;aca ou doen&#231;a pulmonar.<sup><xref ref-type="bibr" rid="B3">3</xref> , <xref ref-type="bibr" rid="B4">4</xref></sup></p>
    </sec>
    <sec sec-type="conclusions">
      <title>Considera&#231;&#227;o</title>
      <p>O teste cardiopulmonar do exerc&#237;cio no BRE, na aus&#234;ncia de outras doen&#231;as card&#237;acas, deve ser considerado como uma t&#233;cnica para avaliar a capacidade de exerc&#237;cio em pacientes com sintomas inexplic&#225;veis.</p>
    </sec>
  </body>
  <back>
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    <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 &#201;tica e Consentimento Informado</p>
        <p>Este artigo n&#227;o cont&#233;m estudos com humanos ou animais realizados por nenhum dos autores.</p>
      </fn>
    </fn-group>
    <fn-group>
      <fn fn-type="financial-disclosure" id="fn6">
        <p>Fontes de Financiamento</p>
        <p>Guimar&#227;es GV foi financiado pelo Conselho Nacional de Desenvolvimento Cient&#237;fico e Tecnol&#243;gico (CNPq: 301957/2017-7).</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>Case Report</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Idiopathic Left-Bundle Branch Block and Unexplained Symptom At Exercise: A Case Report</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-2304-3110</contrib-id>
          <name>
            <surname>Guimar&#227;es</surname>
            <given-names>Guilherme Veiga</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Bocchi</surname>
            <given-names>Edimar Alcides</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1001">
        <label>1</label>
        <country country="BR">Brasil</country>
        <institution content-type="original">Universidade de S&#227;o Paulo Instituto do Cora&#231;&#227;o, S&#227;o Paulo, SP &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c01001">Mailing Address: Guilherme Veiga Guimar&#227;es &#8226; Universidade de S&#227;o Paulo Instituto do Cora&#231;&#227;o &#8211; Av. Dr. Eneas de Carvalho Aguiar, 44. Postal Code 05403-000, S&#227;o Paulo, SP &#8211; Brazil E-mail: gvguima@usp.br</corresp>
        <fn fn-type="con">
          <p>Author Contributions</p>
          <p>Conception and design of the research, Acquisition of data and Critical revision of the manuscript for intellectual content: Guimar&#227;es GV; Analysis and interpretation of the data and Writing of the manuscript: Guimar&#227;es GV, Bocchi EA.</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>
      <kwd-group xml:lang="en">
        <kwd>Bundle Branch Block</kwd>
        <kwd>Exercise</kwd>
        <kwd>Physical Activity</kwd>
        <kwd>Oxygen Consumption/physiology</kwd>
        <kwd>Cardiovascular Diseases/prevention and control</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>The presence of a left bundle branch block (LBBB) in the apparent absence of any other heart disease raises questions and concerns about the stratification of the risk of subsequent cardiovascular events or symptoms.<sup><xref ref-type="bibr" rid="B1">1</xref> - <xref ref-type="bibr" rid="B5">5</xref></sup> The detection of LBBB in asymptomatic adults, including athletes, is estimated to range between 0.1% and 0.8%, which is more likely to represent a structural heart disease rather than a physiological response to exercise.<sup><xref ref-type="bibr" rid="B6">6</xref> - <xref ref-type="bibr" rid="B8">8</xref></sup> On the other hand, some studies have shown that the mortality risk of patients with LBBB and heart disease varies between 2.4% and 11% per year.<sup><xref ref-type="bibr" rid="B9">9</xref></sup></p>
        <p>Although several studies have suggested that exercise-induced LBBB is usually associated with cardiovascular disease and, particularly, coronary artery disease, there are contrasting studies showing an association between exercise-induced LBBB and normal coronary arteries.<sup><xref ref-type="bibr" rid="B6">6</xref> , <xref ref-type="bibr" rid="B7">7</xref> , <xref ref-type="bibr" rid="B9">9</xref></sup> However, exercise-related cardiovascular adverse effects in LBBB with normal resting cardiac function remains poorly defined.</p>
        <p>This case report examined the relationship between exercise, LBBB, symptoms and exercise capacity in a younger woman, with typical LBBB and without history of cardiovascular disease, who reported sudden anxiety and shortness of breath during vigorous exercise, which can be suggestive of cardiac disease, being referred for exercise stress testing.</p>
      </sec>
      <sec>
        <title>Case Report</title>
        <p>A healthy 42-year-old woman with LBBB, who reported sudden anxiety and shortness of breath during vigorous exercise, and was referred for cardiopulmonary exercise testing (CPX) to evaluate the unexplained symptoms. She was not taking any medication and had no significant medical history. She had no previous symptoms suggestive of cardiac disease (chest discomfort, palpitations, fainting and angina). She had no history of neuromuscular or pulmonary disease. She did not smoke or drink alcohol. There was no family history of cardiac disease or heart attack. Over the previous 6 months, she had been exercising three times a week at the gym. The exercise program consisted of sessions of at least 60 min of regular activity at moderate intensity, including aerobic, muscle-strengthening, flexibility, and balance-strengthening exercises. Her physical examination was considered normal, her BMI was 21.5 kg/m<sup>2</sup>and her resting blood pressure was 110/70 mmHg. The resting electrocardiogram (ECG) showed a sinus rhythm (SR) and heart rate (HR) of 70 bpm, with the dominant feature of intraventricular block: prolonged QRS complex (&#8805;0.12s) due to delayed activation of the left ventricle, accompanied by a characteristic morphology of the QRS complex.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> Coronary computed tomography angiography (CTA) was performed, which showed no deposits of calcium and fatty material in the coronary arteries and no stenotic coronary arteries. A complete blood count showed normal results: her fasting glucose was 78 mg/dL, low-density lipoprotein cholesterol (LDL-C) was 168 mg/dL, high-density lipoprotein cholesterol (HDL-C) was 81 mg/dL, total cholesterol was 159 mg/dL, lipoprotein(a) [Lp(a)] was 7 mg/dL, triglycerides were 49 mg/dL and creatine phosphokinase (CPK) was 26 U/L. The magnetic resonance imaging (MRI) of the heart showed normal biventricular function, a left ventricular ejection fraction of 65% and preserved dimensions, except for an abnormal septal motion.</p>
        <p>She underwent CPX on a treadmill. Throughout the CPX phases, the 12-lead ECG showed a SR ( <xref ref-type="fig" rid="f01001">Figure 1</xref> ). Blood pressure measurements were in the normal range: at rest (126/82 mmHg), peak exercise (160/90 mmHg) and recovery stages (120/90 mmHg). She stopped the exercise due to fatigue (RER=1.29). Peak oxygen consumption (VO<sub>2peak</sub>= 27.1 ml/kg/min) and maximum heart rate (HRmax = 176 bpm) values obtained from CPX were normal for age and gender, 95% and 102%, respectively. (https://www.ahajournals.org/doi/10.1161/01.CIR.91.2.580) From stage 14 of the modified Balke protocol until test termination, the CPX identified a decrease in VO<sub>2</sub>and in O<sub>2</sub>pulse (VO<sub>2</sub>/HR, ml/bpm), and an increase in HR and dead space to tidal volume ratio (Vd/Vt) ( <xref ref-type="fig" rid="f02001">Figure 2</xref> ). From this event, the minute ventilation/carbon dioxide production relationship slope (VE/VCO<sub>2</sub>slope) increased abruptly and was not accompanied by hypoxia ( <xref ref-type="fig" rid="f02001">Figure 2</xref> ).</p>
        <p>
          <fig id="f01001">
            <label>Figure 1</label>
            <caption>
              <title>&#8211; Cardiopulmonary exercise test at rest, during exercise and recovery. The black lines indicate the transition between these phases. A) green line - oxygen consumption (VO2/kg, ml/kg/min), red line - heart rate (HR, bpm), black line - oxygen pulse (O2-Pls, ml/bpm) and blue line - respiratory coefficient (RQ); B) green line - minute ventilation (VE, l/min), red line - respiratory rate (RR, bpm), black line - tidal volume (Vt, ml/min) and blue line - dead space to tidal volume ratio (Vd/Vt). C) Minute ventilation/carbon dioxide production relationship slope (VE/VCO2 slope). In the first part of the exercise, VE/VCO2 slope is normal (21); from the event point during the exercise test, the VE/VCO2 slope severely increased (49). Brown line arrow - event point.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-115-1suppl1-0010-90363-gf01-en.tif"/></fig>
        </p>
        <p>
          <fig id="f02001">
            <label>Figure 2</label>
            <caption>
              <title>&#8211; Electrocardiogram demonstrating left bundle branch block: a resting rate of 75 bpm (A), a heart rate of 175 bpm during maximal exercise tolerance test (B) and a heart rate 153 bpm in the first minute of the recovery period (C).</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-115-1suppl1-0010-90363-gf02-en.tif"/></fig>
        </p>
      </sec>
      <sec sec-type="discussion">
        <title>Discussion</title>
        <p>To the best of our knowledge, we report for the first time a younger woman with LBBB without apparent cardiomyopathy and with unexplained symptoms during vigorous exercise (decreased VO<sub>2</sub>, during CPX), which is suggestive of impaired cardiac function in the face of cardiovascular stress. There were no ECG abnormalities except for a LBBB. Heart rate reserve and blood pressure were normal throughout the CPX test.</p>
        <p>Exercise provides a useful tool for the indirect assessment of cardiac functional reserve, from left ventricular performance, the change from rest to peak exercise, and can be limited in the presence of disease. In this context, a drop in the cardiovascular pattern of VO<sub>2</sub>responses may represent impaired cardiac output (CO) or impaired peripheral oxygen extraction as is observed in heart failure.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> On the other hand, in healthy individuals, the level to which oxygen consumption and peripheral oxygen extraction increase in response to exercise is much greater compared to changes in stroke volume and similar to the increase observed in HR.</p>
        <p>The decrease in VO<sub>2</sub>and O<sub>2</sub>pulse, in spite of the increase in HR, observed in this case, may indicate a possible cardiac abnormality. We suggest that the asynchronous motion of the left ventricle associated with delayed wall contraction can reduce the left ventricular workload, resulting in a lower stroke volume and indicating a decrease in cardiac output during maximal exercise, despite the increase in HR.<sup><xref ref-type="bibr" rid="B8">8</xref> - <xref ref-type="bibr" rid="B10">10</xref></sup> This reduction in left ventricular work by an apparent septal perfusion defect during CPX can lead to energy loss and waste of myocardial work, which may represent the hemodynamic impact of asynchronous electrical activation of the myocardium during LBBB,<sup><xref ref-type="bibr" rid="B8">8</xref> - <xref ref-type="bibr" rid="B10">10</xref></sup> and partly explain the drop of VO<sub>2</sub>observed during CPX. On the other hand, exercise-induced left bundle branch block may be related or not to apparent cardiac abnormalities. However, patients with this finding have significantly higher all-cause mortality rates compared to those without exercise-induced left bundle branch block.<sup><xref ref-type="bibr" rid="B11">11</xref></sup></p>
        <p>This apparent decrease in cardiac function during exercise may be due to a transitory decrease in stroke volume, probably related to worsening left ventricular (LV) function associated with an abrupt increase in the VE/VCO<sub>2</sub>slope, giving rise to a higher dead space to tidal volume ratio and an early increase in the respiratory rate, as compensatory mechanisms.<sup><xref ref-type="bibr" rid="B1">1</xref> , <xref ref-type="bibr" rid="B3">3</xref> , <xref ref-type="bibr" rid="B5">5</xref> , <xref ref-type="bibr" rid="B10">10</xref></sup> This disturbance in pathophysiology is linked with LV dysfunction, caused or worsened by LBBB, may indirectly lead to right ventricular dysfunction through increased left-sided filling pressure, causing changes in the function of the lungs&#8217; airways, and to the development of abnormal gas exchange due to alveolar-capillary dysfunction.<sup><xref ref-type="bibr" rid="B3">3</xref> , <xref ref-type="bibr" rid="B4">4</xref></sup> In addition, a higher VE/VCO<sub>2</sub>slope is suggestive of secondary pulmonary hypertension, as a consequence of another primary condition, such as heart failure or pulmonary disease.<sup><xref ref-type="bibr" rid="B3">3</xref> , <xref ref-type="bibr" rid="B4">4</xref></sup></p>
      </sec>
      <sec sec-type="conclusions">
        <title>Consideration</title>
        <p>Cardiopulmonary exercise testing in LBBB, in the absence of other heart diseases, should be considered as a technique to evaluate the exercise capacity in patients with unexplained symptoms.</p>
      </sec>
    </body>
    <back>
      <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 article does not contain any studies with human participants or animals performed by any of the authors.</p>
        </fn>
      </fn-group>
      <fn-group>
        <fn fn-type="financial-disclosure" id="fn6001">
          <p>Sources of Funding</p>
          <p>GV Guimar&#227;es was supported by National Council for Scientific and Technological Development (CNPq:301957/2017-7).</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
