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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">XHZrgCZ9L5sFkWR53F4mPCy</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2023000100202</article-id>
      <article-id pub-id-type="other">00202</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20220864</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>O Raro Padr&#227;o de Pr&#233;-Excita&#231;&#227;o Alternante: Fen&#244;meno Genuinamente Benigno?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-6313-4933</contrib-id>
          <name>
            <surname>Facin</surname>
            <given-names>Mirella</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Samesima</surname>
            <given-names>Nelson</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="orgdiv2">Hospital das Cl&#237;nicas</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina</institution>
        <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Instituto do Cora&#231;&#227;o (InCor) - Hospital das Cl&#237;nicas HCFMUSP - Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c01"> Correspond&#234;ncia: Mirella Facin &#8226; Instituto do Cora&#231;&#227;o (InCor), Hospital das Clinicas FMUSP, Faculdade de Medicina, Universidade de Sao Paulo - Unidade Cl&#237;nica de Eletrocardiografia de Repouso - Av. Dr. En&#233;as de Carvalho Aguiar, 44. CEP 05403-010, S&#227;o Paulo, SP - Brasil E-mail: <email>mirellafacin@gmail.com</email> </corresp>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>10</day>
        <month>02</month>
        <year>2023</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>01</month>
        <year>2023</year>
      </pub-date>
      <volume>120</volume>
      <issue>1</issue>
      <elocation-id>e20220864</elocation-id>
      <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>
      <kwd-group xml:lang="pt">
        <kwd>N&#243; Atrioventricular</kwd>
        <kwd>S&#237;ndrome de Wolff-Parkinson-White</kwd>
        <kwd>Preval&#234;ncia</kwd>
        <kwd>Grau de risco</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="15"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>O sistema de condu&#231;&#227;o &#233; um conjunto de c&#233;lulas mioc&#225;rdicas especializadas, organizadas para gerar e transmitir os est&#237;mulos el&#233;tricos, levando &#224;s contra&#231;&#245;es coordenadas e sequenciais de cada ciclo card&#237;aco.<sup><xref rid="B1" ref-type="bibr">1</xref></sup> Uma espessa camada de tecido fibroso, o <italic>annulus fibrosus</italic> , isola quase totalmente o mioc&#225;rdio atrial do ventricular, exceto na regi&#227;o do nodo atrioventricular (AV) e sistema His-Purkinje que, no cora&#231;&#227;o normal, constitui o &#250;nico caminho el&#233;trico entre as c&#226;maras superiores e inferiores.<sup><xref rid="B1" ref-type="bibr">1</xref> , <xref rid="B2" ref-type="bibr">2</xref> </sup></p>
    <p>Em alguns indiv&#237;duos, entretanto, feixes musculares que conectam diretamente &#225;trios e ventr&#237;culos, remanescentes de etapas anteriores de desenvolvimento card&#237;aco, perduram ap&#243;s o nascimento.<sup><xref rid="B2" ref-type="bibr">2</xref></sup> A presen&#231;a de vias atrioventriculares adicionais ou acess&#243;rias (VA) permite que o est&#237;mulo el&#233;trico contorne o nodo AV, resultando na ativa&#231;&#227;o precoce dos ventr&#237;culos ou pr&#233;-excita&#231;&#227;o. Vias acess&#243;rias podem cruzar o sulco atrioventricular em qualquer ponto de justaposi&#231;&#227;o entre o mioc&#225;rdio atrial e ventricular. A maioria delas tem propriedades de condu&#231;&#227;o bidirecional e n&#227;o decremental, e pode servir como bra&#231;o de circuitos ortodr&#244;micos/antidr&#244;micos reentrantes, ou como via r&#225;pida para a transmiss&#227;o do est&#237;mulo el&#233;trico durante outras taquicardias supraventriculares, tais como a fibrila&#231;&#227;o atrial (FA).<sup><xref rid="B3" ref-type="bibr">3</xref></sup></p>
    <p>A condu&#231;&#227;o anter&#243;grada do ritmo sinusal atrav&#233;s de uma via acess&#243;ria modifica a sequ&#234;ncia temporal e espacial da ativa&#231;&#227;o card&#237;aca, levando a um padr&#227;o eletrocardiogr&#225;fico (ECG) t&#237;pico composto de 1) intervalo PR curto, 2) empastamento inicial do QRS ou onda &#8220;delta&#8221;, e 3) prolongamento do QRS, em n&#237;veis variados de express&#227;o.<sup><xref rid="B4" ref-type="bibr">4</xref> , <xref rid="B5" ref-type="bibr">5</xref> </sup> Descrito pela primeira vez em 1930,<sup><xref rid="B6" ref-type="bibr">6</xref></sup>o padr&#227;o eletrocardiogr&#225;fico de Wolff-Parkinson-White (WPW), ou pr&#233;-excita&#231;&#227;o ventricular, &#233; relativamente raro, com preval&#234;ncia reportada de 1-3:1.000 indiv&#237;duos.<sup><xref rid="B7" ref-type="bibr">7</xref> - <xref rid="B10" ref-type="bibr">10</xref> </sup> Sintomas arr&#237;tmicos ocorrem em um quinto dos pacientes com pr&#233;-excita&#231;&#227;o e definem a s&#237;ndrome de WPW.<sup><xref rid="B5" ref-type="bibr">5</xref></sup></p>
    <p>Palpita&#231;&#245;es, tontura, s&#237;ncope e dor tor&#225;cica s&#227;o apresenta&#231;&#245;es cl&#237;nicas comuns e na maioria das vezes causadas por taquicardias atrioventriculares reentrantes (TAVR). Possivelmente relacionada &#224; instabilidade el&#233;trica inerente &#224;s vias acess&#243;rias, a fibrila&#231;&#227;o atrial incide em 20-30% dos pacientes.<sup><xref rid="B5" ref-type="bibr">5</xref></sup> A condu&#231;&#227;o AV r&#225;pida de arritmias atriais pode degenerar em fibrila&#231;&#227;o ventricular e morte s&#250;bita card&#237;aca (MSC), a manifesta&#231;&#227;o mais temida da s&#237;ndrome WPW.<sup><xref rid="B5" ref-type="bibr">5</xref></sup> Embora eventos de MSC sejam consideravelmente mais frequentes em pacientes com sintomas (risco vital&#237;cio estimado em 4%),<sup><xref rid="B11" ref-type="bibr">11</xref></sup> esse risco n&#227;o &#233; nulo nos portadores assintom&#225;ticos, atingindo quase 0,13% ao ano em uma metan&#225;lise de 1.869 pacientes.<sup><xref rid="B12" ref-type="bibr">12</xref></sup> Epis&#243;dios arr&#237;tmicos s&#227;o ainda mais frequentes em pacientes com pr&#233;-excita&#231;&#227;o ventricular que realizam atividade f&#237;sica extenuante. Embora marcadores n&#227;o invasivos possam contribuir na identifica&#231;&#227;o de vias acess&#243;rias de baixo risco, diretrizes recentes sugerem postergar o treinamento f&#237;sico desses pacientes at&#233; estratifica&#231;&#227;o invasiva adequada.<sup><xref rid="B5" ref-type="bibr">5</xref> , <xref rid="B13" ref-type="bibr">13</xref> </sup> Idade precoce, indutibilidade de taquicardia AV reentrante durante estimula&#231;&#227;o el&#233;trica programada, m&#250;ltiplas vias acess&#243;rias e a demonstra&#231;&#227;o da capacidade da via acess&#243;rias em admitir condu&#231;&#227;o r&#225;pida aos ventr&#237;culos &#8211; menor intervalo R-R pr&#233;-excitado durante FA (SPERRI) &#8804; 250 ms, ou um curto per&#237;odo refrat&#225;rio anter&#243;grado efetivo (PRE) &#8804; 250 ms &#8211; foram associados ao aumento do risco.<sup><xref rid="B5" ref-type="bibr">5</xref> , <xref rid="B13" ref-type="bibr">13</xref> </sup> Reconhecer o padr&#227;o eletrocardiogr&#225;fico de WPW &#233;, portanto, obrigat&#243;rio, mas nem sempre tarefa simples.</p>
    <p>A evid&#234;ncia de pr&#233;-excita&#231;&#227;o ao ECG depende do tempo necess&#225;rio para que o ritmo sinusal alcance o n&#243; AV e a via acess&#243;ria, da velocidade de condu&#231;&#227;o em cada via atrioventricular e de seu PRE.<sup><xref rid="B13" ref-type="bibr">13</xref></sup> Muitos fatores, como localiza&#231;&#227;o da via acess&#243;ria, t&#244;nus auton&#244;mico, dist&#250;rbios metab&#243;licos e drogas, podem afetar as vari&#225;veis mencionadas, tornando din&#226;mica a express&#227;o do padr&#227;o de WPW. Ondas &#8220;delta&#8221; podem ser marcantes, sutis, impercept&#237;veis, ou mesmo desaparecer de tempos em tempos. Deveras, a pr&#233;-excita&#231;&#227;o intermitente &#233; relatada em at&#233; 15% dos casos.<sup><xref rid="B14" ref-type="bibr">14</xref></sup> Um representante curioso deste fen&#244;meno &#233; a pr&#233;-excita&#231;&#227;o alternante, na qual complexos QRS alargados e com onda delta se alternam com QRS normais, batimento a batimento, no mesmo tra&#231;ado eletrocardiogr&#225;fico, um importante diagn&#243;stico diferencial de outras causas de altern&#226;ncia do QRS, como bloqueio de ramo intermitente, bigeminismo atrial e ventricular. Dados sobre essa apresenta&#231;&#227;o particular do padr&#227;o WPW eram escassos e aned&#243;ticos, dispon&#237;veis em alguns relatos de caso. No entanto, Lim et al. abordaram consistentemente a preval&#234;ncia de pr&#233;-excita&#231;&#227;o alternante nos registros m&#233;dicos pr&#233;-participa&#231;&#227;o de mais de 125 mil recrutas militares do sexo masculino.<sup><xref rid="B15" ref-type="bibr">15</xref></sup> O padr&#227;o WPW ocorreu em 184 (0,147%) indiv&#237;duos, frequ&#234;ncia semelhante &#224; relatada por extensos estudos epidemiol&#243;gicos. Dentre os portadores do padr&#227;o WPW, a pr&#233;-excita&#231;&#227;o alternante foi reportada em apenas em quatro (2,2%) pacientes &#8211; dois desses desenvolveram sintomas relacionados a TAVR. Embora a perda intermitente da pr&#233;-excita&#231;&#227;o tenha sido historicamente associada a vias acess&#243;rias de baixo risco, estudos recentes em sujeitos sintom&#225;ticos e assintom&#225;ticos demonstraram que mais de um quinto dos pacientes com padr&#227;o WPW intermitente apresentaram vias acess&#243;rias com PRE &lt;250 ms.<sup><xref rid="B15" ref-type="bibr">15</xref></sup> Infelizmente, Lim et al. n&#227;o puderam fornecer informa&#231;&#245;es sobre estratifica&#231;&#227;o de risco dessa forma t&#227;o particular de pr&#233;-excita&#231;&#227;o, devido ao pequeno n&#250;mero de pacientes com padr&#227;o WPW alternante, &#224; aus&#234;ncia de informa&#231;&#245;es eletrofisiol&#243;gicas invasivas e ao limitado per&#237;odo de seguimento de seu trabalho.<sup><xref rid="B15" ref-type="bibr">15</xref></sup> S&#227;o necess&#225;rios mais estudos para confirmar a preval&#234;ncia relatada de pr&#233;-excita&#231;&#227;o alternante e avaliar seu impacto progn&#243;stico.</p>
  </body>
  <back>
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    <fn-group>
      <fn id="fn1">
        <p>
          <italic>Minieditorial refere-se ao artigo: 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</italic>
        </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>Short Editorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>The Rare Alternans Pre-Excitation Pattern: Is It a Genuinely Benign Phenomenon?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-6313-4933</contrib-id>
          <name>
            <surname>Facin</surname>
            <given-names>Mirella</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Samesima</surname>
            <given-names>Nelson</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">Brazil</country>
        <institution content-type="original">Instituto do Cora&#231;&#227;o (InCor) - Hospital das Cl&#237;nicas HCFMUSP - Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c01001">Mailing Address: Mirella Facin &#8226; Instituto do Cora&#231;&#227;o (InCor), Hospital das Clinicas FMUSP, Faculdade de Medicina, Universidade de Sao Paulo &#8211; Unidade Cl&#237;nica de Eletrocardiografia de Repouso &#8211; Av. Dr. En&#233;as de Carvalho Aguiar, 44. Postal Code 05403-010, S&#227;o Paulo, SP &#8211; Brazil E-mail: mirellafacin@gmail.com</corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <kwd>Atrioventricular Node</kwd>
        <kwd>Wolff-Parkinson-White Syndrome</kwd>
        <kwd>Prevalence</kwd>
        <kwd>Risk Grade</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>The conduction system is a specialized myocardial cell arrangement that neatly generates and transmits electrical stimuli, leading to sequentially coordinated contractions in each cardiac cycle.<sup><xref rid="B1" ref-type="bibr">1</xref></sup>A thick layer of fibrous tissue, the annulus fibrosus, almost entirely insulates the atrial from the ventricular myocardia, except in the region of the atrioventricular (AV) node and His-Purkinje system, which, in normal hearts, stands as the single electric pathway between the upper and lower chambers.<sup><xref rid="B1" ref-type="bibr">1</xref> , <xref rid="B2" ref-type="bibr">2</xref> </sup></p>
      <p>In some individuals, however, threads of myocardial tissue directly connecting atria to ventricles remain from previous developmental stages and endure after childbirth.<sup><xref rid="B2" ref-type="bibr">2</xref></sup>The presence of additional atrioventricular conduits or accessory pathways (AP) allows the electrical stimuli to bypass the AV node, resulting in earlier activation of the ventricles or pre-excitation. Bypass tracts may cross the atrioventricular groove wherever atrial and ventricular myocardium are juxtaposed. Most are capable of bidirectional and non-decremental conduction and may serve as a limb to reentrant orthodromic/antidromic circuits or fast lanes for impulse transmission during other supraventricular tachycardias, such as atrial fibrillation (AF).<sup><xref rid="B3" ref-type="bibr">3</xref></sup></p>
      <p>The antegrade sinus rhythm conduction through an accessory pathway modifies the temporal and spatial sequence of cardiac activation, leading to a typical electrocardiographic (ECG) pattern composed of 1) a short PR interval, 2) initial QRS slurring or &#8220;delta&#8221; wave, and 3) QRS enlargement, in various degrees of expression.<sup><xref rid="B4" ref-type="bibr">4</xref> , <xref rid="B5" ref-type="bibr">5</xref> </sup>First described in 1930,<sup><xref rid="B6" ref-type="bibr">6</xref></sup>the so-called pre-excitation or Wolff-Parkinson-White (WPW) pattern is relatively rare, accounting for 1-3:1000 individuals.<sup><xref rid="B7" ref-type="bibr">7</xref> - <xref rid="B10" ref-type="bibr">10</xref> </sup>Arrhythmic symptoms occur in one-fifth of the patients with pre-excitation and define the WPW syndrome.<sup><xref rid="B5" ref-type="bibr">5</xref></sup></p>
      <p>Palpitations, light-headedness, syncope, and thoracic pain are common clinical presentations and often relate to reentrant atrioventricular tachycardias. Possibly triggered by the electrical instability inherent to APs, atrial fibrillation arises in 20-30% of patients.<sup><xref rid="B5" ref-type="bibr">5</xref></sup>The rapid AV conduction of atrial arrhythmias may degenerate into ventricular fibrillation, leading to sudden cardiac death (SCD), WPW syndrome&#8217;s most feared manifestation.<sup><xref rid="B5" ref-type="bibr">5</xref></sup>The risk of SCD is considerably high for patients with symptoms, approaching 4% over a lifetime;<sup><xref rid="B11" ref-type="bibr">11</xref></sup>yet, it is not null in asymptomatic carriers, reaching almost 0.13% per year in a meta-analysis comprising 1869 patients.<sup><xref rid="B12" ref-type="bibr">12</xref></sup>Pre-excitation-related arrhythmic events are even more frequent in patients undergoing strenuous physical activity. Albeit non-invasive markers could add to the identification of low-risk APs, recent guidelines suggest postponing exercise training in those patients until proper invasive risk stratification.<sup><xref rid="B5" ref-type="bibr">5</xref> , <xref rid="B13" ref-type="bibr">13</xref> </sup>Younger age, inducibility of AV-reentrant tachycardia during programmed electrical stimulation, numerous accessory pathways, and demonstration of the bypass tract capability to admit rapid conduction to ventricles &#8211; i.e., shortest pre-excited RR interval during AF (SPERRI) of &#8804; 250 ms at baseline or an AP short antegrade effective refractory period (ERP) of &#8804; 250 ms &#8211; were associated to increased risk.<sup><xref rid="B5" ref-type="bibr">5</xref> , <xref rid="B13" ref-type="bibr">13</xref> </sup>Recognizing the WPW ECG pattern is hence mandatory but not always straightforward.</p>
      <p>The extent to which pre-excitation is evident on ECG depends on the time taken for the sinus rhythm to reach the AV node and the accessory pathway, on the conduction velocity in each atrioventricular trail, and their ERP.<sup><xref rid="B13" ref-type="bibr">13</xref></sup>Many factors, such as AP location, autonomic tone, metabolic disturbances, and drugs, can affect the abovementioned variables and make the WPW pattern expression dynamic. &#8220;Delta&#8221; waves can be marked or subtle, maybe unnoticed, even disappearing from time to time. Indeed, intermittent pre-excitation is reported in up to 15% of cases.<sup><xref rid="B14" ref-type="bibr">14</xref></sup>A curious representative of this phenomenon is the alternans pre-excitation, in which enlarged delta-waved QRS complexes alternate with normal ones, on a beat-to-beat basis, in the same ECG trace, an important differential diagnosis to other causes of QRS alternans, such as intermittent branch block, atrial and ventricular bigeminy. Data on this particular WPW pattern presentation was scarce and anecdotal, available in a few case reports. However, Lim et al. consistently addressed alternans pre-excitation prevalence by reviewing the pre-participation medical files from over 125 thousand male military recruits.<sup><xref rid="B15" ref-type="bibr">15</xref></sup>WPW pattern occurred in 184 (0.147%) individuals, a frequency similar to that of extensive epidemiologic studies. Beneath the cases of WPW pattern, alternans pre-excitation was rare, occurring in only four (2.2%) patients &#8211; half of them further developed AVRT-related symptoms. Although the intermittent loss of pre-excitation has historically been associated with low-risk AP, recent studies with both symptomatic and asymptomatic subjects demonstrated that over one-fifth of patients with intermittent WPW pattern presented AP ERP &lt;250 ms.<sup><xref rid="B15" ref-type="bibr">15</xref></sup>Unfortunately, Lim et al. could not provide information on risk stratification due to the small number of patients presenting alternans pre-excitation, the absence of invasive electrophysiologic information, and the limited follow-up period in their study.<sup><xref rid="B15" ref-type="bibr">15</xref></sup>More studies are needed to confirm the reported prevalence of alternans pre-excitation and evaluate its impact on patient prognosis.</p>
    </body>
    <back>
      <fn-group>
        <fn id="fn1001">
          <p>
            <italic>Short Editorial related to the article: Wolff-Parkinson-White Presenting as QRS Alternans and Other Differential Diagnoses in a Large Pre-Participation ECG Screening Cohort</italic>
          </p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
