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  <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">rZGVt4hZWVhS6vbSHF7kZRm</article-id>
      <article-id specific-use="previous-pid" pub-id-type="publisher-id">S0066-782X2022005018202</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2022001300940</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20220081</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo Original</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Wolff-Parkinson-White Apresentado como QRS Alternante e Outros Diagn&#243;sticos Diferenciais em uma Grande Coorte de Triagem de ECG Pr&#233;-Participa&#231;&#227;o</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-9715-6970</contrib-id>
          <name>
            <surname>Lim</surname>
            <given-names>Daniel Y. Z.</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Obten&#231;&#227;o de dados</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>An&#225;lise estat&#237;stica</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ho</surname>
            <given-names>Wilbert H. H.</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Obten&#231;&#227;o de dados</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Wang</surname>
            <given-names>Luokai</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
          <xref ref-type="aff" rid="aff3">
            <sup>3</sup>
          </xref>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ang</surname>
            <given-names>Wee Kiat</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <role>Obten&#231;&#227;o de dados</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Thiagarajan</surname>
            <given-names>Nishanth</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <role>Obten&#231;&#227;o de dados</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Sng</surname>
            <given-names>Gerald GR</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <role>Obten&#231;&#227;o de dados</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Wang</surname>
            <given-names>Hankun</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <role>Obten&#231;&#227;o de dados</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Loo</surname>
            <given-names>Wesley TW</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <role>Obten&#231;&#227;o de dados</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Yang</surname>
            <given-names>Lim Huai</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Chow</surname>
            <given-names>Weien</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Chua</surname>
            <given-names>Terrance J</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">
            <sup>3</sup>
          </xref>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Yeo</surname>
            <given-names>Tee Joo</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff4">
            <sup>4</sup>
          </xref>
          <xref ref-type="aff" rid="aff5">
            <sup>5</sup>
          </xref>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lim</surname>
            <given-names>Paul</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff3">
            <sup>3</sup>
          </xref>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Chong</surname>
            <given-names>Thuan Tee Daniel</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff3">
            <sup>3</sup>
          </xref>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante</role>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgdiv2">Medical Classification Centre</institution>
        <institution content-type="orgdiv1">Central Manpower Base</institution>
        <institution content-type="orgname">Singapore Armed Forces</institution>
        <country country="SG">Cingapura</country>
        <institution content-type="original">Medical Classification Centre, Central Manpower Base, Singapore Armed Forces, Cingapura</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgdiv1">HQ Medical Corps</institution>
        <institution content-type="orgname">Singapore Armed Forces</institution>
        <country country="SG">Cingapura</country>
        <institution content-type="original">HQ Medical Corps, Singapore Armed Forces, Cingapura</institution>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution content-type="orgdiv1">Department of Cardiology</institution>
        <institution content-type="orgname">National Heart Centre Singapore</institution>
        <country country="SG">Cingapura</country>
        <institution content-type="original">Department of Cardiology, National Heart Centre Singapore, Cingapura</institution>
      </aff>
      <aff id="aff4">
        <label>4</label>
        <institution content-type="orgdiv1">Department of Cardiology</institution>
        <institution content-type="orgname">National University Heart Centre Singapore</institution>
        <country country="SG">Cingapura</country>
        <institution content-type="original">Department of Cardiology, National University Heart Centre Singapore, Cingapura</institution>
      </aff>
      <aff id="aff5">
        <label>5</label>
        <institution content-type="orgdiv1">University Medicine Cluster</institution>
        <institution content-type="orgname">National University Health System</institution>
        <country country="SG">Cingapura</country>
        <institution content-type="original">University Medicine Cluster, National University Health System, Cingapura</institution>
      </aff>
      <author-notes>
        <corresp id="c01"> Correspond&#234;ncia: Daniel YZ Lim &#8226; Singapore Health Service - Outram Road Singapore Singapore Singapore 168751 Cingapura E-mail: <email>daniel.lim@mohh.com.sg</email> </corresp>
        <fn fn-type="conflict">
          <p>Potencial conflito de interesse</p>
          <p>N&#227;o h&#225; conflito com o presente artigo</p>
        </fn>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>21</day>
        <month>11</month>
        <year>2022</year>
      </pub-date>
      <pub-date publication-format="electronic" date-type="collection">
        <month>12</month>
        <year>2022</year>
      </pub-date>
      <volume>119</volume>
      <issue>6</issue>
      <fpage>940</fpage>
      <lpage>945</lpage>
      <history>
        <date date-type="received">
          <day>03</day>
          <month>02</month>
          <year>2022</year>
        </date>
        <date date-type="rev-recd">
          <day>12</day>
          <month>05</month>
          <year>2022</year>
        </date>
        <date date-type="accepted">
          <day>10</day>
          <month>08</month>
          <year>2022</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 License, which permits unrestricted 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> A s&#237;ndrome de Wolff-Parkinson-White (WPW) &#233; uma condi&#231;&#227;o pr&#243;-arr&#237;tmica que pode exigir restri&#231;&#227;o de atividades extenuantes e &#233; caracterizada por sinais de ECG, incluindo ondas delta. Observamos casos de padr&#245;es intermitentes de WPW apresentando-se como QRS alternante (&#8216;WPW alternante&#8217;) em uma grande coorte de triagem de ECG pr&#233;-participa&#231;&#227;o de homens jovens que se candidataram ao recrutamento militar.</p>
        </sec>
        <sec>
          <title>Objetivos</title>
          <p> Nosso objetivo foi determinar o padr&#227;o de WPW alternante, as caracter&#237;sticas do caso e a preval&#234;ncia de outros diagn&#243;sticos diferenciais relevantes apresentando-se como altern&#226;ncia de QRS em um ambiente de pr&#233;-participa&#231;&#227;o.</p>
        </sec>
        <sec>
          <title>M&#233;todos</title>
          <p> Cento e vinte e cinco mil cento e cinquenta e oito recrutas militares do sexo masculino prospectivos foram revisados de janeiro de 2016 a dezembro de 2019. Uma revis&#227;o de prontu&#225;rios m&#233;dicos eletr&#244;nicos identificou casos de WPW alternante e padr&#245;es ou s&#237;ndrome de WPW. A revis&#227;o de prontu&#225;rios m&#233;dicos eletr&#244;nicos identificou casos de diagn&#243;sticos diferenciais relevantes que podem causar altern&#226;ncia de QRS.</p>
        </sec>
        <sec>
          <title>Resultados</title>
          <p> Quatro indiv&#237;duos (2,2%) apresentaram WPW alternante em 184 indiv&#237;duos com diagn&#243;stico final de padr&#227;o ou s&#237;ndrome de WPW. Dois desses indiv&#237;duos manifestaram sintomas ou achados eletrocardiogr&#225;ficos compat&#237;veis com taquicardia supraventricular. A preval&#234;ncia geral de WPW alternante foi de 0,003%, e a preval&#234;ncia de WPW foi de 0,147%. As WPW alternantes representaram 8,7% dos indiv&#237;duos com QRS alternantes, e QRS alternantes tiveram preval&#234;ncia de 0,037% em toda a popula&#231;&#227;o.</p>
        </sec>
        <sec>
          <title>Conclus&#245;es</title>
          <p> A WPW alternante &#233; uma variante da WPW intermitente, que compreendeu 2,2% dos casos de WPW em nossa coorte de triagem pr&#233;-participa&#231;&#227;o. N&#227;o indica necessariamente um baixo risco de taquicardia supraventricular. Deve ser reconhecido na triagem de ECG e distinguido de outras patologias que tamb&#233;m apresentam QRS alternantes.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <kwd>S&#237;ndrome de Wolf-Parkinson-White</kwd>
        <kwd>S&#237;ndrome do Complexo PR curto-QRS normal</kwd>
        <kwd>Pr&#233;-Excita&#231;&#227;o Tipo Mahaim</kwd>
        <kwd>Eletrocardiografia/m&#233;todos</kwd>
        <kwd>Eletrocardiografia/diagn&#243;stico</kwd>
      </kwd-group>
      <counts>
        <fig-count count="2"/>
        <table-count count="2"/>
        <equation-count count="0"/>
        <ref-count count="18"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>A avalia&#231;&#227;o f&#237;sica pr&#233;-participa&#231;&#227;o antes de atividades extenuantes, como esportes, pode permitir a detec&#231;&#227;o de condi&#231;&#245;es m&#233;dicas potencialmente desqualificantes, como anormalidades card&#237;acas graves. A triagem eletrocardiogr&#225;fica (ECG) &#233; uma das modalidades utilizadas nessas avalia&#231;&#245;es para detectar condi&#231;&#245;es pr&#243;-arr&#237;tmicas. &#201; recomendado por v&#225;rias sociedades profissionais e diretrizes,<sup><xref ref-type="bibr" rid="B1">1</xref> - <xref ref-type="bibr" rid="B3">3</xref></sup> com crit&#233;rios de interpreta&#231;&#227;o, incluindo os crit&#233;rios<sup><xref ref-type="bibr" rid="B4">4</xref></sup> da European Society of Cardiology (ESC) 2010, Seattle Criteria,<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Refined Criteria,<sup><xref ref-type="bibr" rid="B6">6</xref></sup> e, mais recentemente, os Crit&#233;rios Internacionais para interpreta&#231;&#227;o de ECG em Atletas.<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
      <p>Wolff-Parkinson-White (WPW) &#233; uma condi&#231;&#227;o potencialmente pr&#243;-arr&#237;tmica que pode ser detectada na triagem de ECG. A anormalidade subjacente &#233; uma via acess&#243;ria que permite a condu&#231;&#227;o dos &#225;trios para os ventr&#237;culos, contornando o n&#243; atrioventricular. Essa pr&#233;-excita&#231;&#227;o se manifesta como ondas delta, intervalo PR curto, intervalo QRS prolongado e anormalidades de repolariza&#231;&#227;o no ECG. O padr&#227;o WPW no ECG em combina&#231;&#227;o com taquiarritmia sintom&#225;tica constitui a s&#237;ndrome WPW. Indiv&#237;duos com WPW requerem revis&#227;o e estratifica&#231;&#227;o de risco antes de participar de atividades extenuantes. O padr&#227;o WPW convencional &#233; prontamente reconhec&#237;vel pela pr&#233;-excita&#231;&#227;o em cada batimento, mas raramente pode apresentar pr&#233;-excita&#231;&#227;o intermitente em batimentos alternados (ou seja, com QRS alternante, definido pela altern&#226;ncia de amplitude, morfologia ou dura&#231;&#227;o do complexo QRS). Esse fen&#244;meno pode dificultar o reconhecimento, existindo apenas relatos de casos isolados do fen&#244;meno &#8216;WPW alternante&#8217; na literatura.<sup><xref ref-type="bibr" rid="B8">8</xref> - <xref ref-type="bibr" rid="B10">10</xref></sup> Esses casos foram identificados esporadicamente, em vez de coletados sistematicamente.</p>
      <p>A altern&#226;ncia WPW tamb&#233;m deve ser distinguida de outras etiologias de altern&#226;ncia QRS. Em situa&#231;&#245;es de emerg&#234;ncia, um diagn&#243;stico diferencial chave que &#233; classicamente descrito &#233; o tamponamento peric&#225;rdico (onde h&#225; QRS alternante devido &#224; oscila&#231;&#227;o mec&#226;nica do &#225;pice card&#237;aco em vez da patologia das vias de condu&#231;&#227;o intr&#237;nsecas). Outras situa&#231;&#245;es em que o QRS alternante pode ocorrer em ritmos n&#227;o estimulados incluem pausa sinusal intermitente/bloqueio de sa&#237;da com escape ventricular ou escape juncional com bloqueio de ramo (BR), BR intermitente em batimentos alternados, bigeminismo atrial com condu&#231;&#227;o aberrante e bigeminismo ventricular. Tamb&#233;m pode ocorrer durante taquiarritmias, como taquicardia ventricular bidirecional e taquicardia supraventricular em altas frequ&#234;ncias (por exemplo, taquicardia por reentrada atrioventricular).</p>
      <p>Nenhuma literatura examinou sistematicamente a preval&#234;ncia de WPW alternante ou QRS alternante em um ambiente de pr&#233;-participa&#231;&#227;o, n&#227;o emergencial. No entanto, continua sendo necess&#225;rio que os m&#233;dicos que realizam a triagem de ECG reconhe&#231;am corretamente WPW alternante como uma forma de WPW, distingam-no de outras causas de QRS alternante e, a partir da&#237;, determinem se a causa subjacente justifica a exclus&#227;o da participa&#231;&#227;o.</p>
      <p>As For&#231;as Armadas de Cingapura realizaram triagem universal de ECG pr&#233;-participa&#231;&#227;o antes do alistamento militar para todos os jovens cingapurianos do sexo masculino para determinar a aptid&#227;o card&#237;aca.<sup><xref ref-type="bibr" rid="B11">11</xref> - <xref ref-type="bibr" rid="B13">13</xref></sup> Nosso objetivo principal foi determinar sistematicamente a preval&#234;ncia do padr&#227;o WPW alternante e as caracter&#237;sticas relevantes do caso neste cen&#225;rio de pr&#233;-participa&#231;&#227;o, n&#227;o emergencial. Nosso objetivo secund&#225;rio foi determinar sistematicamente a preval&#234;ncia de outros diagn&#243;sticos diferenciais relevantes apresentando-se como QRS alternante no mesmo cen&#225;rio.</p>
    </sec>
    <sec sec-type="methods">
      <title>M&#233;todos</title>
      <p>Cento e vinte e cinco mil cento e cinquenta e oito recrutas militares do sexo masculino em potencial foram revisados de janeiro de 2016 a dezembro de 2019 como parte de sua determina&#231;&#227;o de aptid&#227;o para se alistar no servi&#231;o militar. Todos os indiv&#237;duos compareceram ao mesmo servi&#231;o centralizado e realizaram ECG de 12 deriva&#231;&#245;es em dec&#250;bito dorsal. Os ECGs foram informados por m&#233;dicos treinados usando um algoritmo padronizado baseado nos Crit&#233;rios Internacionais.<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
      <p>Durante este per&#237;odo, observamos quatro casos de WPW alternante no ECG apresentado. Revisamos as refer&#234;ncias eletr&#244;nicas ao centro terci&#225;rio nacional de cardiologia para suspeita de padr&#245;es de ECG de WPW e os registros m&#233;dicos eletr&#244;nicos dos 184 indiv&#237;duos que receberam um novo padr&#227;o de WPW ou diagn&#243;stico de s&#237;ndrome. N&#227;o foram identificados outros casos de altern&#226;ncia WPW. Separadamente, identificamos 34 indiv&#237;duos que haviam sido diagnosticados com WPW antes de participar da triagem pr&#233;-participa&#231;&#227;o. Esses casos foram exclu&#237;dos de nossa an&#225;lise porque seus ECGs n&#227;o estavam dispon&#237;veis. Esses 34 indiv&#237;duos tiveram ECGs repetidos em nosso centro de triagem, dos quais nenhum apresentou WPW alternante.</p>
      <p>Concomitantemente, identificamos indiv&#237;duos com QRS alternante de outras etiologias. Determinamos isso por dois meios: primeiro, por uma revis&#227;o da documenta&#231;&#227;o de texto feita para a interpreta&#231;&#227;o cl&#237;nica do ECG; segundo, por uma revis&#227;o dos c&#243;digos diagn&#243;sticos para arritmias card&#237;acas e tamponamento peric&#225;rdico. Com o primeiro m&#233;todo, empregamos uma pesquisa por palavra-chave e uma revis&#227;o manual do gr&#225;fico de toda a documenta&#231;&#227;o. Os termos de pesquisa para as v&#225;rias condi&#231;&#245;es est&#227;o listados no <ext-link ext-link-type="uri" xlink:href="http://abccardiol.org/supplementary-material/2022/11906/2022-0081-supp-material.pdf">Ap&#234;ndice 1</ext-link> e s&#227;o baseados no vocabul&#225;rio padronizado de interpreta&#231;&#227;o de ECG de nossas instala&#231;&#245;es. Extra&#237;mos os prontu&#225;rios eletr&#244;nicos de indiv&#237;duos com os c&#243;digos de diagn&#243;stico relevantes com o segundo m&#233;todo. Isso garantiu a identifica&#231;&#227;o exaustiva de indiv&#237;duos com morfologia QRS alternante. Todos os indiv&#237;duos identificados com WPW alternantes e QRS alternantes tiveram seus ECG revisados manualmente.<sup><xref ref-type="bibr" rid="B14">14</xref></sup></p>
      <p>A aprova&#231;&#227;o para coleta e uso de dados foi concedida pelo Comit&#234; M&#233;dico Conjunto das For&#231;as Armadas de Cingapura e a aprova&#231;&#227;o &#233;tica foi obtida do conselho de revis&#227;o institucional local.</p>
      <sec>
        <title>An&#225;lise estat&#237;stica</title>
        <p>Adotou-se uma abordagem descritiva, calculando a preval&#234;ncia de WPW alternante na popula&#231;&#227;o geral e indiv&#237;duos com WPW. Tamb&#233;m calculamos a preval&#234;ncia de QRS alternante na popula&#231;&#227;o geral e os diagn&#243;sticos individuais causadores de QRS alternante. A an&#225;lise quantitativa foi feita usando Excel (Microsoft 365 Apps). Os detalhes de casos de indiv&#237;duos com WPW alternante s&#227;o apresentados qualitativamente.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Resultados</title>
      <p>Quatro indiv&#237;duos (2,2%) apresentaram WPW alternante em 184 indiv&#237;duos com diagn&#243;stico final de padr&#227;o ou s&#237;ndrome de WPW. Em toda a coorte de triagem, a preval&#234;ncia de WPW alternante foi de 0,003% e a preval&#234;ncia de WPW foi de 0,147%.</p>
      <p>Tamb&#233;m identificamos outros 42 indiv&#237;duos com morfologia de QRS alternante a partir de revis&#227;o de prontu&#225;rios na triagem de ECG. Este incluiu 1 indiv&#237;duo com BR intermitente em batimentos alternados, 9 indiv&#237;duos com bigeminismo atrial e 32 com bigeminismo ventricular. Nenhum indiv&#237;duo apresentou bloqueio/pausa sinusal intermitente com escape ventricular, escape juncional com BR ou taquicardia ventricular ao apresentar ECG. Nenhum indiv&#237;duo em nossa coorte teve diagn&#243;stico ativo de tamponamento peric&#225;rdico no momento da triagem. No geral, os WPW alternantes representaram 8,7% dos indiv&#237;duos que apresentavam QRS alternantes, e os QRS alternantes tiveram uma preval&#234;ncia de 0,037% em toda a popula&#231;&#227;o de triagem de ECG. Todos os indiv&#237;duos identificados n&#227;o tinham doen&#231;a card&#237;aca pr&#233;-existente. Essas descobertas s&#227;o resumidas por meio de um diagrama de fluxo na <xref ref-type="fig" rid="f01">Figura 1</xref> .</p>
      <p>
        <fig id="f01">
          <label>Figura 1</label>
          <caption>
            <title>Fluxograma dos indiv&#237;duos inclu&#237;dos no estudo. ECG: eletrocardiogr&#225;fica; TSV: taquicardia supraventricular; WPW: Wolff-Parkinson-White..</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-119-06-0940-20081-gf01.jpg"/></fig>
      </p>
      <p>Apresentamos na <xref ref-type="table" rid="t1">Tabela 1</xref> os detalhes do caso dos quatro indiv&#237;duos com WPW alternantes. No momento da reda&#231;&#227;o deste artigo, nenhum dos indiv&#237;duos havia consentido em estudos eletrofisiol&#243;gicos invasivos e nenhum havia sofrido morte s&#250;bita card&#237;aca. Todos foram aconselhados a n&#227;o se envolverem em atividades fisicamente extenuantes.</p>
      <p>
        <table-wrap id="t1">
          <label>Tabela 1</label>
          <caption>
            <title>Detalhes do caso WPW alternante</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead>
              <tr>
                <th align="left" style="font-weight:normal"> </th>
                <th>Caso 1</th>
                <th>Caso 2</th>
                <th>Caso 3</th>
                <th>Caso 4</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>ECG na triagem</td>
                <td align="center" colspan="4">Por favor, consulte o Ap&#234;ndice 2 para ECGs de cada caso</td>
              </tr>
              <tr>
                <td>Idade</td>
                <td align="center">19</td>
                <td align="center">19</td>
                <td align="center">18</td>
                <td align="center">18</td>
              </tr>
              <tr>
                <td>Sintomas</td>
                <td align="center">Palpita&#231;&#245;es Sem s&#237;ncope</td>
                <td align="center">Palpita&#231;&#245;es Sem s&#237;ncope</td>
                <td align="center">Palpita&#231;&#245;es Sem s&#237;ncope</td>
                <td align="center">Sem sintomas</td>
              </tr>
              <tr>
                <td>Presen&#231;a de taquicardia supraventricular</td>
                <td align="center">Sim Teve palpita&#231;&#245;es consideradas clinicamente compat&#237;veis com taquicardia supraventricular</td>
                <td align="center">Sim Desenvolveu taquicardia RP longo durante a consulta &#8211; diagnosticada como taquicardia atrial</td>
                <td align="center">N&#227;o</td>
                <td align="center">N&#227;o</td>
              </tr>
              <tr>
                <td>Teste de esfor&#231;o em esteira</td>
                <td align="center">Pr&#233;-excitado com pr&#233;-excita&#231;&#227;o intermitente</td>
                <td align="center">Pr&#233;-excitado com perda de pr&#233;-excita&#231;&#227;o na FC m&#225;xima de 194 bpm</td>
                <td align="center">Pr&#233;-excitado sem perda s&#250;bita de pr&#233;-excita&#231;&#227;o</td>
                <td align="center">Normal</td>
              </tr>
              <tr>
                <td>Ecocardiograma 2D</td>
                <td align="center">Normal</td>
                <td align="center">Normal</td>
                <td align="center">Normal</td>
                <td align="center">N&#227;o realizada</td>
              </tr>
              <tr>
                <td>Outras investiga&#231;&#245;es</td>
                <td align="center">Holter 24 horas: pr&#233;-excita&#231;&#227;o intermitente</td>
                <td align="center">Nada</td>
                <td align="center">Holter 24 horas: pr&#233;-excita&#231;&#227;o intermitente</td>
                <td align="center">Nada</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN1">
              <p>
                <italic>ECG: eletrocardiogr&#225;fica; FC: frequ&#234;ncia card&#237;aca. RP: intervalo de onda R para P.</italic>
              </p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </p>
    </sec>
    <sec sec-type="discussion">
      <title>Discuss&#227;o</title>
      <p>A triagem de ECG pr&#233;-participa&#231;&#227;o eficaz requer o reconhecimento de padr&#245;es anormais, incluindo apresenta&#231;&#245;es incomuns de anormalidades de ECG. Nossa casu&#237;stica de quatro indiv&#237;duos com WPW alternantes mostrou preval&#234;ncia de 2,2% entre os casos de WPW e 0,003% em toda a coorte. At&#233; onde sabemos, esta &#233; a maior s&#233;rie de casos de WPW alternantes na literatura e o &#250;nico estudo que determinou sistematicamente sua preval&#234;ncia. Isso sugere que WPW alternante pode n&#227;o ser t&#227;o raro quanto sua escassez na literatura existente sugere.</p>
      <p>A WPW alternante &#233; uma forma de pr&#233;-excita&#231;&#227;o intermitente, convencionalmente pensada para conferir menor risco de taquicardia supraventricular.<sup><xref ref-type="bibr" rid="B15">15</xref></sup> N&#227;o observamos isso em nossa s&#233;rie de casos - na verdade, o caso 2 desenvolveu epis&#243;dios de taquicardia supraventricular (TSV) durante a consulta de triagem. Foi cardiovertido com manobras vagais e encaminhado de emerg&#234;ncia ao centro terci&#225;rio nacional de cardiologia. O caso 4 apresentou palpita&#231;&#245;es recorrentes que o cardiologista respons&#225;vel considerou compat&#237;veis com TSV parox&#237;stica. Evid&#234;ncia de Escudero et al.,<sup><xref ref-type="bibr" rid="B15">15</xref></sup> em um recente estudo de WPW multic&#234;ntrico pedi&#225;trico<sup><xref ref-type="bibr" rid="B16">16</xref></sup> sugere que a pr&#233;-excita&#231;&#227;o intermitente n&#227;o &#233; totalmente isenta de risco, e esses indiv&#237;duos ainda podem ter vias acess&#243;rias subjacentes com alto risco de desenvolver TSV. Portanto, &#233; importante que o padr&#227;o WPW alternante seja adequadamente reconhecido no momento da triagem de ECG e n&#227;o seja erroneamente considerado benigno. Deve ser concedido o mesmo tratamento que qualquer outro caso de WPW.</p>
      <p>O reconhecimento de WPW alternante pode ser confundido por outras patologias que apresentam o padr&#227;o QRS alternante. Como esperado de uma coorte jovem, pr&#233;-participa&#231;&#227;o, n&#227;o emergencial, n&#227;o foram diagnosticados casos de patologias agudas graves, como taquicardia ventricular bidirecional ou tamponamento card&#237;aco. O bigeminismo ventricular foi a patologia alternativa mais comum, seguido pelo bigeminismo atrial e BR intermitente em batimentos alternados. Exemplos de ECGs de tais condi&#231;&#245;es coletadas de indiv&#237;duos nesta arte de coorte inclu&#237;dos no <ext-link ext-link-type="uri" xlink:href="http://abccardiol.org/supplementary-material/2022/11906/2022-0081-supp-material.pdf">Ap&#234;ndice 3</ext-link>. A &#250;nica maneira de distinguir WPW dessas outras patologias &#233; examinar cuidadosamente o ECG para ondas delta. Como tal, os m&#233;dicos examinadores devem estar atentos a esses outros diagn&#243;sticos diferenciais e considerar ECGs seriados para elicita&#231;&#227;o adicional de ondas delta.</p>
      <p>A principal for&#231;a do nosso estudo &#233; que foi uma pesquisa abrangente, em toda a popula&#231;&#227;o, realizada ao longo de v&#225;rios anos. &#201; o primeiro estudo a examinar sistematicamente a epidemiologia do padr&#227;o WPW alternante no cen&#225;rio de triagem de ECG e a documentar a epidemiologia de importantes diagn&#243;sticos diferenciais que tamb&#233;m podem se apresentar com QRS alternante. Isso ajudar&#225; os m&#233;dicos que realizam a triagem de ECG a chegar a um diagn&#243;stico diferencial relevante para o sinal visualmente marcante de QRS alternante, pois as patologias observadas n&#227;o s&#227;o as mesmas descritas em configura&#231;&#245;es de emerg&#234;ncia.</p>
      <p>Nosso estudo tem algumas limita&#231;&#245;es importantes. Primeiro, os ECGs do estudo foram revisados por diferentes m&#233;dicos, e a equipe do estudo n&#227;o revisou pessoalmente todos os ECGs do banco de dados. Pode haver varia&#231;&#227;o interindividual na interpreta&#231;&#227;o do ECG entre os m&#233;dicos. Em segundo lugar, notamos que a WPW n&#227;o tem predile&#231;&#227;o por g&#234;nero em grupos et&#225;rios pedi&#225;tricos,<sup><xref ref-type="bibr" rid="B17">17</xref></sup> mas &#233; conhecida por ter uma predomin&#226;ncia masculina em adultos.<sup><xref ref-type="bibr" rid="B18">18</xref></sup> A preval&#234;ncia relativa de nossa coorte de adolescentes do sexo masculino pode, portanto, n&#227;o ser totalmente generaliz&#225;vel para indiv&#237;duos do sexo feminino. No entanto, o reconhecimento correto do sinal de ECG alternante e WPW alternante ainda seria importante para indiv&#237;duos do sexo feminino submetidos &#224; triagem de ECG. Terceiro, n&#227;o podemos confirmar nenhum mecanismo eletrofisiol&#243;gico espec&#237;fico de WPW alternante, pois nenhum dos indiv&#237;duos identificados consentiu em um estudo eletrofisiol&#243;gico invasivo. Finalmente, n&#227;o podemos comentar sobre o risco de morte s&#250;bita card&#237;aca em longo prazo para os indiv&#237;duos com WPW ou WPW alternantes neste estudo, uma vez que os indiv&#237;duos examinados tinham sido diagnosticados apenas nos &#250;ltimos anos. Estudos futuros podem incluir um acompanhamento prolongado desses indiv&#237;duos para melhor verificar seu risco de morte s&#250;bita card&#237;aca.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclus&#227;o</title>
      <p>WPW alternante &#233; uma apresenta&#231;&#227;o variante de WPW intermitente, que ocorreu em 2,2% dos casos de WPW em uma coorte de triagem pr&#233;-participa&#231;&#227;o. N&#227;o indica necessariamente um baixo risco de taquicardia supraventricular. Portanto, deve ser reconhecida na triagem de ECG e distinguido de outras patologias que tamb&#233;m apresentam QRS alternante. Nos diagn&#243;sticos diferenciais comuns de QRS alternante observados em nossa pr&#233;-participa&#231;&#227;o, a coorte n&#227;o emergencial incluiu bigeminismo ventricular, bigeminismo atrial e BR intermitente em batimentos alternados.</p>
    </sec>
  </body>
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        <p>Vincula&#231;&#227;o acad&#234;mica</p>
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    </fn-group>
    <fn-group>
      <fn fn-type="supported-by">
        <p>Fontes de financiamento: O presente estudo n&#227;o teve fontes de financiamento externas.</p>
      </fn>
    </fn-group>
    <app-group>
      <app id="app1">
        <title>* Material suplementar</title>
        <p>Para informa&#231;&#227;o adicional, por favor,<ext-link ext-link-type="uri" xlink:href="http://abccardiol.org/supplementary-material/2022/11906/2022-0081-supp-material.pdf">clique aqui</ext-link>.</p>
      </app>
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  </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>Wolff-Parkinson-White Presenting as QRS Alternans and Other Differential Diagnoses in a Large Pre-Participation ECG Screening Cohort</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-9715-6970</contrib-id>
          <name>
            <surname>Lim</surname>
            <given-names>Daniel Y. Z.</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <role>Conception and design of the research</role>
          <role>Acquisition of data</role>
          <role>Analysis and interpretation of the data</role>
          <role>Statistical analysis</role>
          <role>Writing of the manuscript</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ho</surname>
            <given-names>Wilbert H. H.</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <role>Conception and design of the research</role>
          <role>Acquisition of data</role>
          <role>Analysis and interpretation of the data</role>
          <role>Writing of the manuscript</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Wang</surname>
            <given-names>Luokai</given-names>
          </name>
          <xref ref-type="aff" rid="aff2001">
            <sup>2</sup>
          </xref>
          <xref ref-type="aff" rid="aff3001">
            <sup>3</sup>
          </xref>
          <role>Analysis and interpretation of the data</role>
          <role>Critical revision of the manuscript for important intellectual content</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ang</surname>
            <given-names>Wee Kiat</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <role> Acquisition of data</role>
          <role>Writing of the manuscript</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Thiagarajan</surname>
            <given-names>Nishanth</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <role>Acquisition of data</role>
          <role>Writing of the manuscript</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Sng</surname>
            <given-names>Gerald GR</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <role>Acquisition of data</role>
          <role>Critical revision of the manuscript for important intellectual content</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Wang</surname>
            <given-names>Hankun</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <role>Acquisition of data</role>
          <role>Critical revision of the manuscript for important intellectual content</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Loo</surname>
            <given-names>Wesley TW</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <role>Acquisition of data</role>
          <role>Critical revision of the manuscript for important intellectual content</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Yang</surname>
            <given-names>Lim Huai</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <role>Critical revision of the manuscript for important intellectual content</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Chow</surname>
            <given-names>Weien</given-names>
          </name>
          <xref ref-type="aff" rid="aff2001">
            <sup>2</sup>
          </xref>
          <role>Critical revision of the manuscript for important intellectual content</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Chua</surname>
            <given-names>Terrance J</given-names>
          </name>
          <xref ref-type="aff" rid="aff3001">
            <sup>3</sup>
          </xref>
          <role>Critical revision of the manuscript for important intellectual content</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Yeo</surname>
            <given-names>Tee Joo</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff4001">
            <sup>4</sup>
          </xref>
          <xref ref-type="aff" rid="aff5001">
            <sup>5</sup>
          </xref>
          <role>Critical revision of the manuscript for important intellectual content</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lim</surname>
            <given-names>Paul</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff3001">
            <sup>3</sup>
          </xref>
          <role>Critical revision of the manuscript for important intellectual content</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Chong</surname>
            <given-names>Thuan Tee Daniel</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff3001">
            <sup>3</sup>
          </xref>
          <role>Critical revision of the manuscript for important intellectual content</role>
        </contrib>
      </contrib-group>
      <aff id="aff1001">
        <label>1</label>
        <country country="SG">Singapore</country>
        <institution content-type="original">Medical Classification Centre, Central Manpower Base, Singapore Armed Forces, Singapore</institution>
      </aff>
      <aff id="aff2001">
        <label>2</label>
        <country country="SG">Singapore</country>
        <institution content-type="original">HQ Medical Corps, Singapore Armed Forces, Singapore</institution>
      </aff>
      <aff id="aff3001">
        <label>3</label>
        <country country="SG">Singapore</country>
        <institution content-type="original">Department of Cardiology, National Heart Centre Singapore, Singapore</institution>
      </aff>
      <aff id="aff4001">
        <label>4</label>
        <country country="SG">Singapore</country>
        <institution content-type="original">Department of Cardiology, National University Heart Centre Singapore, Singapore</institution>
      </aff>
      <aff id="aff5001">
        <label>5</label>
        <country country="SG">Singapore</country>
        <institution content-type="original">University Medicine Cluster, National University Health System, Singapore</institution>
      </aff>
      <author-notes>
        <corresp id="c01001">Mailing Address: Daniel Y. Z. Lim &#8226; Singapore Health Service &#8211; Outram Road Singapore 168751 E-mail: daniel.lim@mohh.com.sg</corresp>
        <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>Wolff-Parkinson-White (WPW) syndrome is a proarrhythmic condition that may require restriction from strenuous activities and is characterized by ECG signs, including delta waves. We observed cases of intermittent WPW patterns presenting as QRS alternans (&#8216;WPW alternans&#8217;) in a large pre-participation ECG screening cohort of young men reporting for military conscription.</p>
        </sec>
        <sec>
          <title>Objectives</title>
          <p>We aimed to determine the WPW alternans pattern, case characteristics, and the prevalence of other relevant differential diagnoses presenting as QRS alternans in a pre-participation setting.</p>
        </sec>
        <sec>
          <title>Methods</title>
          <p>One hundred twenty-five thousand one hundred fifty-eight prospective male military recruits were reviewed from January 2016 to December 2019. A review of electronic medical records identified cases of WPW alternans and WPW patterns or syndrome. Reviewing electronic medical records identified cases of relevant differential diagnoses that might cause QRS alternans.</p>
        </sec>
        <sec>
          <title>Results</title>
          <p>Four individuals (2.2%) had WPW alternans out of 184 individuals with a final diagnosis of WPW pattern or syndrome. Two of these individuals manifested symptoms or ECG findings consistent with supraventricular tachycardia. The overall prevalence of WPW alternans was 0.003%, and the prevalence of WPW was 0.147%. WPW alternans represented 8.7% of individuals presenting with QRS alternans, and QRS alternans had a prevalence of 0.037% in the entire population.</p>
        </sec>
        <sec>
          <title>Conclusions</title>
          <p>WPW alternans is a variant of intermittent WPW, which comprised 2.2% of WPW cases in our pre-participation screening cohort. It does not necessarily indicate a low risk for supraventricular tachycardia. It must be recognized at ECG screening and distinguished from other pathologies that also present with QRS alternans.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Wolff-Parkinson-White Syndrome</kwd>
        <kwd>Lown &#8211; Ganong &#8211; Levine Syndrome</kwd>
        <kwd>Pre-Excitation, Mahaim-Type</kwd>
        <kwd>Electrocardiography/methods</kwd>
        <kwd>Electrocardiography/diagnosis</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>Preparticipation physical evaluation prior to strenuous activities such as sports may allow for the detection of potentially disqualifying medical conditions, such as serious cardiac abnormalities. Electrocardiographic (ECG) screening is one of the modalities used in such evaluations to detect proarrhythmic conditions. It is recommended by multiple professional societies and guidelines,<sup><xref ref-type="bibr" rid="B1">1</xref> - <xref ref-type="bibr" rid="B3">3</xref></sup> with interpretation criteria including the European Society of Cardiology (ESC) 2010 criteria,<sup><xref ref-type="bibr" rid="B4">4</xref></sup> Seattle Criteria,<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Refined Criteria (2014)<sup><xref ref-type="bibr" rid="B6">6</xref></sup> and most recently, the International Criteria for ECG interpretation in Athletes (2017).<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
        <p>Wolff-Parkinson-White (WPW) is a potentially proarrhythmic condition that can be detected on ECG screening. The underlying abnormality is an accessory pathway that allows conduction from the atria to the ventricles, bypassing the atrioventricular node. This pre-excitation manifests as delta waves, short PR interval, prolonged QRS interval, and repolarization abnormalities on ECG. The WPW pattern on ECG in combination with symptomatic tachyarrhythmia constitutes WPW syndrome. Individuals with WPW require review and risk stratification before participating in strenuous activities. The conventional WPW pattern is readily recognizable by pre-excitation on every beat but can rarely present intermittent pre-excitation on alternate beats (i.e., with QRS alternans, defined by alternating amplitude, morphology, or duration of the QRS complex). This phenomenon may make recognition challenging, and only isolated case reports exist of the &#8216;WPW alternans&#8217; phenomenon in the literature.<sup><xref ref-type="bibr" rid="B8">8</xref> - <xref ref-type="bibr" rid="B10">10</xref></sup> These cases were sporadically identified rather than systematically collected.</p>
        <p>WPW alternans must also be distinguished from other etiologies of QRS alternans. In emergency settings, a key differential diagnosis that is classically described is pericardial tamponade (where there are QRS alternans due to mechanical swinging of the cardiac apex rather than the pathology of the intrinsic conduction pathways). Other situations in which QRS alternans may occur in non-paced rhythms include intermittent sinus pause/ exit block with ventricular escape or junctional escape with bundle branch block (BBB), intermittent BBB on alternate beats, atrial bigeminy with aberrant conduction and ventricular bigeminy. It may also occur during tachyarrhythmias such as bidirectional ventricular tachycardia and supraventricular tachycardias at high rates (e.g., atrioventricular re-entrant tachycardia).</p>
        <p>No literature has systematically examined the prevalence of WPW alternans or QRS alternans in a pre-participation, non-emergency setting. However, it remains necessary for medical providers conducting ECG screening to correctly recognize WPW alternans as a form of WPW, distinguish it from other causes of QRS alternans, and thence determine if the underlying cause warrants exclusion from participation.</p>
        <p>The Singapore Armed Forces have conducted universal pre-participation ECG screening before military enlistment for all young male Singaporeans to determine cardiac fitness.<sup><xref ref-type="bibr" rid="B11">11</xref> - <xref ref-type="bibr" rid="B13">13</xref></sup> Our primary aim was to systematically determine the prevalence of the WPW alternans pattern and the relevant case characteristics in this pre-participation, non-emergency setting. Our secondary aim was to systematically determine the prevalence of other relevant differential diagnoses presenting as QRS alternans in the same setting.</p>
      </sec>
      <sec sec-type="methods">
        <title>Methods</title>
        <p>One hundred twenty-five thousand one hundred fifty-eight prospective male military recruits were reviewed from January 2016 to December 2019 as part of their determination of fitness to enlist in military service. All individuals attended the same centralized facility and had a supine resting 12-lead ECG. The ECGs were reported by trained clinicians using a standardized algorithm based on International Criteria.<sup><xref ref-type="bibr" rid="B7">7</xref></sup></p>
        <p>During this period, we observed four cases of WPW alternans on the presenting ECG. We reviewed electronic referrals to the national cardiology tertiary center for suspected WPW ECG patterns and the electronic medical records of the 184 individuals who had received a new WPW pattern or syndrome diagnosis. No other cases of WPW alternans were identified. Separately, we identified 34 individuals who had been diagnosed with WPW prior to attending the pre-participation screening. These cases were excluded from our analysis because their presenting ECGs were unavailable. These 34 individuals had repeat ECGs at our screening center, of which none displayed WPW alternans.</p>
        <p>Concurrently, we identified individuals presenting with QRS alternans arising from other etiologies. We determined this through two means: First, by a review of text documentation made for clinical ECG interpretation; Second, by a review of diagnostic codes for cardiac arrhythmias and pericardial tamponade. With the first method, we employed a keyword search and a manual chart review of all documentation. The search terms for the various conditions are listed in <ext-link ext-link-type="uri" xlink:href="http://abccardiol.org/supplementary-material/2022/11906/2022-0081-supp-material.pdf">Appendix 1</ext-link> and are based on our facility&#8217;s standardized ECG interpretation vocabulary. We extracted the electronic medical records for individuals with the relevant diagnosis codes with the second method. This ensured exhaustive identification of individuals with QRS alternans morphology. All individuals identified with WPW alternans and QRS alternans had their ECG manually reviewed.</p>
        <p>Approval for data collection and use was granted by the Singapore Armed Forces Joint Medical Committee, and ethical approval was obtained from the local institutional review board.</p>
        <sec>
          <title>Statistical analysis</title>
          <p>We adopted a descriptive approach, calculating the prevalence of WPW alternans in the overall population and individuals with WPW. We also calculated the prevalence of QRS alternans in the overall population and the individual diagnoses causing QRS alternans. Quantitative analysis was done using Excel (Microsoft 365 Apps). Case details of individuals with WPW alternans are qualitatively presented.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Results</title>
        <p>Four individuals (2.2%) had WPW alternans out of 184 individuals with a final diagnosis of WPW pattern or syndrome. In the entire screening cohort, the prevalence of WPW alternans was 0.003%, and the prevalence of WPW was 0.147%.</p>
        <p>We also identified 42 other individuals with QRS alternans morphology from medical records review on screening ECG. This comprised 1 individual with intermittent BBB on alternating beats, 9 individuals with atrial bigeminy, and 32 with ventricular bigeminy. No individuals had intermittent sinus pause/exit block with ventricular escape, junctional escape with BBB, or ventricular tachycardia on presenting ECG. No individuals in our cohort had an active diagnosis of pericardial tamponade at the point of screening. Overall, WPW alternans represented 8.7% of individuals presenting with QRS alternans, and QRS alternans had a prevalence of 0.037% in the entire ECG screening population. All of the individuals identified did not have pre-existing cardiac disease. These findings are summarized via a flow diagram in <xref ref-type="fig" rid="f01001">Figure 1</xref> .</p>
        <p>
          <fig id="f01001">
            <label>Figure 1</label>
            <caption>
              <title>Flow diagram of individuals included in the study. ECG: electrocardiographic; WPW: Wolff-Parkinson-White; SVT: supraventricular tachycardia.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-119-06-0940-20081-gf01-en.jpg"/></fig>
        </p>
        <p>We present in <xref ref-type="table" rid="t1001">Table 1</xref> the case details of the four individuals with WPW alternans. At the time of writing, none of the individuals had consented to invasive electrophysiology studies, and none had experienced any sudden cardiac death. All were advised not to engage in physically strenuous activities.</p>
        <p>
          <table-wrap id="t1001">
            <label>Table 1</label>
            <caption>
              <title>WPW alternans case details</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left" style="font-weight:normal"> </th>
                  <th>Case 1</th>
                  <th>Case 2</th>
                  <th>Case 3</th>
                  <th>Case 4</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>ECG at screening</td>
                  <td align="center" colspan="4">Please refer to Appendix 2 for ECGs of each case</td>
                </tr>
                <tr>
                  <td>Age</td>
                  <td align="center">19</td>
                  <td align="center">19</td>
                  <td align="center">18</td>
                  <td align="center">18</td>
                </tr>
                <tr>
                  <td>Symptoms</td>
                  <td align="center">Palpitations No syncope</td>
                  <td align="center">Palpitations No syncope</td>
                  <td align="center">Palpitations No syncope</td>
                  <td align="center">No symptoms</td>
                </tr>
                <tr>
                  <td>Presence of supraventricular tachycardia</td>
                  <td align="center">Yes Had palpitations deemed clinically compatible with supraventricular tachycardia</td>
                  <td align="center">Yes Developed long RP tachycardia during consult &#8211; diagnosed as atrial tachycardia</td>
                  <td align="center">No</td>
                  <td align="center">No</td>
                </tr>
                <tr>
                  <td>Treadmill exercise test</td>
                  <td align="center">Pre-excited with intermittent pre-excitation</td>
                  <td align="center">Pre-excited with loss of pre-excitation at maximal HR of 194 bpm</td>
                  <td align="center">Pre-excited with no sudden loss of pre-excitation</td>
                  <td align="center">Normal</td>
                </tr>
                <tr>
                  <td>2D Echocardiogram</td>
                  <td align="center">Normal</td>
                  <td align="center">Normal</td>
                  <td align="center">Normal</td>
                  <td align="center">Not performed</td>
                </tr>
                <tr>
                  <td>Other investigations</td>
                  <td align="center">24 hour Holter: intermittent pre-excitation</td>
                  <td align="center">Nil</td>
                  <td align="center">24 hour Holter: intermittent pre-excitation</td>
                  <td align="center">Nil</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN1001">
                <p>
                  <italic>ECG: Electrocardiographic ; HR: heart rate; RP: R to P wave interval.</italic>
                </p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </p>
      </sec>
      <sec sec-type="discussion">
        <title>Discussion</title>
        <p>Effective pre-participation ECG screening requires recognizing abnormal patterns, including uncommon presentations of ECG abnormalities. Our case series of four individuals with WPW alternans showed a prevalence of 2.2% among WPW cases and 0.003% in the entire cohort. To our knowledge, this is the largest case series of WPW alternans in the literature and the only study that has systematically determined its prevalence. It suggests that WPW alternans may not be as rare as its paucity in the extant literature suggests.</p>
        <p>WPW alternans is a form of intermittent pre-excitation, which is conventionally thought to confer a lower risk of supraventricular tachycardia.<sup><xref ref-type="bibr" rid="B15">15</xref></sup> We did not observe this in our case series - in fact, Case 2 developed episodes of supraventricular tachycardia (SVT) during the screening consultation. He was cardioverted with vagal maneuvers and emergently referred to the national cardiology tertiary center. Case 4 had recurrent palpitations that the attending cardiologist deemed consistent with paroxysmal SVT. Evidence from Escudero et al.<sup><xref ref-type="bibr" rid="B15">15</xref></sup> in a recent multicenter pediatric WPW study<sup><xref ref-type="bibr" rid="B16">16</xref></sup> suggests that intermittent pre-excitation is not entirely risk-free, and such individuals may still have underlying accessory pathways at high risk for developing the SVT. It is thus important that the WPW alternans pattern is adequately recognized at the point of ECG screening and not mistakenly deemed benign. It should be accorded the same treatment as any other case of WPW.</p>
        <p>Recognition of WPW alternans may be confounded by other pathologies presenting with the QRS alternans pattern. As expected of a young, pre-participation, non-emergency cohort, no cases of severe acute pathologies such as bidirectional ventricular tachycardia or cardiac tamponade were diagnosed. Ventricular bigeminy was the most common alternative pathology, followed by atrial bigeminy and intermittent BBB on alternate beats. Example ECGs of such conditions gathered from individuals in this cohort art included in <ext-link ext-link-type="uri" xlink:href="http://abccardiol.org/supplementary-material/2022/11906/2022-0081-supp-material.pdf">Appendix 3</ext-link>. The only way to distinguish WPW from these other pathologies is to examine the ECG for delta waves carefully. As such, examiner physicians must be alert to these other differential diagnoses and consider serial ECGs for further elicitation of delta waves.</p>
        <p>The main strength of our study is that it was a comprehensive, population-wide survey conducted over multiple years. It is the first study to systematically examine the epidemiology of the WPW alternans pattern in the ECG screening setting and to document the epidemiology of important differential diagnoses that can also present with QRS alternans. This will aid clinicians performing ECG screening in arriving at a relevant differential diagnosis for the visually striking sign of QRS alternans, as the pathologies observed are not the same as those described in emergency settings.</p>
        <p>Our study has some important limitations. First, the ECGs in the study were reviewed by different clinicians, and the study team did not personally review every ECG in the database. There may be inter-individual variation in ECG interpretation between clinicians. Second, we note that WPW has no gender predilection in pediatric age groups<sup><xref ref-type="bibr" rid="B17">17</xref></sup> but is known to have a male predominance in adults.<sup><xref ref-type="bibr" rid="B18">18</xref></sup> The relative prevalence of our cohort of adolescent males may thus not be entirely generalizable to female individuals. However, correct recognition of the alternans ECG sign and WPW alternans would still be important for female individuals undergoing ECG screening. Third, we cannot confirm any specific electrophysiologic mechanism of WPW alternans, as none of the individuals identified consented to an invasive electrophysiologic study. Finally, we cannot comment on the long-term sudden cardiac death risk for the individuals with WPW or WPW alternans in this study, given that the individuals examined had only been diagnosed within the last few years. Future studies may include extended follow-up for such individuals to ascertain their sudden cardiac death risk better.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclusion</title>
        <p>WPW alternans is a variant presentation of intermittent WPW, which occurred in 2.2% of WPW cases in a pre-participation screening cohort. It does not necessarily indicate a low risk for supraventricular tachycardia. Hence, it must be recognized at ECG screening and distinguished from other pathologies that also present with QRS alternans. Common differential diagnoses of QRS alternans observed in our pre-participation, the non-emergency cohort included ventricular bigeminy, atrial bigeminy and intermittent BBB on alternate beats.</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 study was approved by the Ethics Committee of the SingHealth Centralised IRB under the protocol number 2015/3095. 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-group>
      <fn-group>
        <fn fn-type="supported-by">
          <p>Sources of Funding: There were no external funding sources for this study.</p>
        </fn>
      </fn-group>
      <app-group>
        <app id="app01">
          <title>* Supplemental Materials</title>
          <p>For additional information, please <ext-link ext-link-type="uri" xlink:href="http://abccardiol.org/supplementary-material/2022/11906/2022-0081-supp-material.pdf">click here</ext-link>.</p>
        </app>
      </app-group>
    </back>
  </sub-article>
</article>
