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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">N6fxG8Ld75tbNJpSntnFtzG</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2022001000531</article-id>
      <article-id pub-id-type="publisher-id">abc.20220619</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20220619</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Dist&#250;rbios de Condu&#231;&#227;o ap&#243;s o Implante Transcateter de V&#225;lvula A&#243;rtica: Desafio para mais 20 Anos?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Pozetti</surname>
            <given-names>Antonio H&#233;lio</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-1273-1823</contrib-id>
          <name>
            <surname>Ribeiro</surname>
            <given-names>Henrique Barbosa</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
      </contrib-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 do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo , S&#227;o Paulo , SP &#8211; Brasil </institution>
      </aff>
      <aff id="aff2">
        <label> 2 </label>
        <institution content-type="orgname">Hospital Samaritano Paulista</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"> Hospital Samaritano Paulista , S&#227;o Paulo , SP &#8211; Brasil </institution>
      </aff>
      <author-notes>
        <corresp id="c01">Correspond&#234;ncia: Henrique Barbosa Ribeiro &#8226; Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo &#8211; Av. Dr. En&#233;as Carvalho de Aguiar, 44. CEP 05403-900, Cerqueira C&#233;sar, S&#227;o Paulo, SP &#8211; Brasil E-mail: <email>henrique.ribeiro@hc.fm.usp.br</email> </corresp>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>21</day>
        <month>10</month>
        <year>2022</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>10</month>
        <year>2022</year>
      </pub-date>
      <volume>119</volume>
      <issue>4</issue>
      <fpage>531</fpage>
      <lpage>532</lpage>
      <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>TAVI</kwd>
        <kwd>Marca-passo</kwd>
        <kwd>Dist&#250;rbios de Condu&#231;&#227;o</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="14"/>
        <page-count count="2"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>O implante transcateter de v&#225;lvula a&#243;rtica (TAVI) &#233; um procedimento bem estabelecido para o tratamento da estenose a&#243;rtica grave, independente do risco cir&#250;rgico para pacientes idosos. <sup><xref ref-type="bibr" rid="B1">1</xref></sup> Desde sua introdu&#231;&#227;o h&#225; duas d&#233;cadas houve grandes avan&#231;os tecnol&#243;gicos nos dispositivos, que aliados a novas t&#233;cnicas de implante trouxeram redu&#231;&#245;es significativas nas taxas de complica&#231;&#245;es periprocedimento, impulsionando sua maior ado&#231;&#227;o mundialmente. No entanto, a incid&#234;ncia dos dist&#250;rbios de condu&#231;&#227;o apresentou redu&#231;&#227;o modesta, permanecendo como a complica&#231;&#227;o mais frequente ap&#243;s o TAVI, <sup><xref ref-type="bibr" rid="B2">2</xref> - <xref ref-type="bibr" rid="B4">4</xref></sup> o que contribui para o aumento da perman&#234;ncia hospitalar, dos custos e da piora dos desfechos cl&#237;nicos a curto e longo prazos. <sup><xref ref-type="bibr" rid="B4">4</xref> , <xref ref-type="bibr" rid="B5">5</xref></sup> Al&#233;m disso, a abordagem dos dist&#250;rbios de condu&#231;&#227;o ainda tem grande varia&#231;&#227;o entre os centros, principalmente em rela&#231;&#227;o ao manejo do bloqueio de ramo esquerdo (BRE) novo, bloqueio atrioventricular avan&#231;ado (BAV) p&#243;s procedimento e bloqueio de ramo direito (BRD) pr&#233;vio, traduzido em taxas vari&#225;veis de implante de marca-passo definitivo (MP). <sup><xref ref-type="bibr" rid="B3">3</xref></sup> Entre os pacientes que receberam MP ap&#243;s o TAVI tamb&#233;m h&#225; grande variabilidade com respeito &#224; sua depend&#234;ncia (estimula&#231;&#227;o ventricular) no seguimento.</p>
    <p>Nesta edi&#231;&#227;o do jornal, Pinto et al. <sup><xref ref-type="bibr" rid="B6">6</xref></sup> avaliaram a incid&#234;ncia de dist&#250;rbios de condu&#231;&#227;o, preditores e a taxa de depend&#234;ncia do MP, em uma popula&#231;&#227;o de 340 pacientes consecutivos submetidos a TAVI. <sup><xref ref-type="bibr" rid="B6">6</xref></sup> Os dist&#250;rbios de condu&#231;&#227;o ocorreram em mais de 50% dos pacientes p&#243;s procedimento, sendo o BRE o mais frequente (32%), com resolu&#231;&#227;o espont&#226;nea em 56% deles ap&#243;s 6 meses. A taxa global de implante de MP foi de 18,5%, sendo o BRD pr&#233;vio seu principal preditor. Entre os pacientes que necessitaram de MP, as principais raz&#245;es foram BAV avan&#231;ado (60,3%), seguido do BRE com BAV de baixo grau (22%). De maneira interessante, houve grande varia&#231;&#227;o na porcentagem de estimula&#231;&#227;o ventricular entre os pacientes que receberam MP, sendo de 83% nos pacientes com BAV avan&#231;ado (BAVT e Mobitz II) e de apenas 2% naqueles implantados por BRE e BAV de baixo grau (BAV de primeiro grau e Mobitz tipo I). Os resultados deste estudo refor&#231;am os dados da literatura que demonstram a elevada incid&#234;ncia dos dist&#250;rbios de condu&#231;&#227;o em cerca da metade dos pacientes ap&#243;s o TAVI e a necessidade de MP definitivo em quase 20% deles. <sup><xref ref-type="bibr" rid="B2">2</xref> - <xref ref-type="bibr" rid="B4">4</xref> , <xref ref-type="bibr" rid="B7">7</xref></sup> Contudo, alguns aspectos deste estudo merecem uma reflex&#227;o.</p>
    <p>Em primeiro lugar, a avalia&#231;&#227;o pr&#233;-procedimento &#233; fundamental para identificarmos fatores de risco para dist&#250;rbios de condu&#231;&#227;o e auxiliar a estrat&#233;gia do operador. Assim como demonstrado por Pinto et al., <sup><xref ref-type="bibr" rid="B6">6</xref></sup> a presen&#231;a de BRD pr&#233;vio (~10% dos pacientes) <sup><xref ref-type="bibr" rid="B8">8</xref></sup> &#233; o principal fator de risco para implante de MP p&#243;s TAVI, aumentando sua incid&#234;ncia em 3 a 4 vezes, <sup><xref ref-type="bibr" rid="B8">8</xref> , <xref ref-type="bibr" rid="B9">9</xref></sup> sendo tamb&#233;m um preditor de mortalidade p&#243;s-procedimento. <sup><xref ref-type="bibr" rid="B9">9</xref></sup> No presente estudo o BRE e o BAV de primeiro grau pr&#233;vios n&#227;o se correlacionaram com maior necessidade de MP, diferentemente de outros autores que em n&#250;mero maior de pacientes, demonstraram que o BRE pode ter impacto na necessidade de MP nos primeiros 30 dias, mas n&#227;o no seguimento ap&#243;s 30 dias, por&#233;m sem impacto em mortalidade. <sup><xref ref-type="bibr" rid="B8">8</xref> , <xref ref-type="bibr" rid="B10">10</xref></sup></p>
    <p>Um segundo ponto importante refere-se ao procedimento, no qual alguns aspectos modific&#225;veis tamb&#233;m podem influenciar nas taxas de dist&#250;rbios de condu&#231;&#227;o. Por exemplo, metade dos dist&#250;rbios de condu&#231;&#227;o ocorrem antes do implante da v&#225;lvula, principalmente durante a pr&#233;-dilata&#231;&#227;o, sugerindo alguma correla&#231;&#227;o com valvoplastia por bal&#227;o, <sup><xref ref-type="bibr" rid="B11">11</xref></sup> como tamb&#233;m evidenciado no presente estudo. Al&#233;m disso, foi demonstrado que as v&#225;lvulas de nova gera&#231;&#227;o e t&#233;cnicas para implantes mais altos no anel propiciaram redu&#231;&#245;es significativas nas taxas de MP para &lt;10%. <sup><xref ref-type="bibr" rid="B7">7</xref> , <xref ref-type="bibr" rid="B8">8</xref> , <xref ref-type="bibr" rid="B12">12</xref></sup> De fato, Pinto et al. <sup><xref ref-type="bibr" rid="B6">6</xref></sup> demostram uma redu&#231;&#227;o de quase 50% com as pr&#243;teses de nova gera&#231;&#227;o, e na presen&#231;a de biopr&#243;tese cir&#250;rgica disfuncionante ( <italic>valve-in-valve</italic> ). <sup><xref ref-type="bibr" rid="B13">13</xref></sup></p>
    <p>Ao final do procedimento um eletrocardiograma (ECG) de 12 deriva&#231;&#245;es deve ser realizado para determinar a conduta frente aos eventuais dist&#250;rbios de condu&#231;&#227;o, bem como a monitoriza&#231;&#227;o cont&#237;nua por 12-24 horas. <sup><xref ref-type="bibr" rid="B2">2</xref></sup> Assim como visto por Pinto et al. <sup><xref ref-type="bibr" rid="B6">6</xref></sup> o principal dist&#250;rbio de condu&#231;&#227;o &#233; o BRE, sendo que 10-15% evoluem para MP no primeiro ano, <sup><xref ref-type="bibr" rid="B9">9</xref></sup> refor&#231;ando a import&#226;ncia da monitoriza&#231;&#227;o ambulatorial destes casos. Posto a isso, recomenda-se a avalia&#231;&#227;o seriada dos ECG, sendo que em casos de aumento dos intervalos PR ou QRS &gt; 20 ms, especialmente na presen&#231;a de PR&gt;240 ms e QRS&gt;150 ms pode-se indicar o implante de MP profil&#225;tico pelo risco de morte s&#250;bita e BAV avan&#231;ado. <sup><xref ref-type="bibr" rid="B2">2</xref></sup> No estudo de Pinto et al. <sup><xref ref-type="bibr" rid="B6">6</xref></sup> 22% das indica&#231;&#245;es de MP foram por BRE combinado com BAV primeiro grau, por&#233;m este grupo apresentou apenas 2% de estimula&#231;&#227;o ventricular em 1 ano, demonstrando a dificuldade em conduzir este tipo de paciente bem como a real necessidade do marcapasso em determinadas circunst&#226;ncias, uma vez que apesar da baixa estimula&#231;&#227;o, ela tenha ocorrido durante epis&#243;dios parox&#237;ticos de BAV avan&#231;ado ou bradicardia extrema com risco de vida.</p>
    <p>Apesar de duas d&#233;cadas de avan&#231;o tecnol&#243;gico e melhora dos resultados da TAVI, os dist&#250;rbios de condu&#231;&#227;o ainda permanecem como principal complica&#231;&#227;o p&#243;s TAVI. Diversos estudos nos &#250;ltimos anos contribu&#237;ram para a identifica&#231;&#227;o dos fatores de risco, permitindo uma redu&#231;&#227;o das taxas de MP e tem auxiliado no manejo desses pacientes. Embora o estudo de Pinto et al. <sup><xref ref-type="bibr" rid="B6">6</xref></sup> apresente algumas limita&#231;&#245;es (retrospectivo, observacional e unic&#234;ntrico), ele refor&#231;a o BRD pr&#233;vio como principal fator de risco para necessidade de MP e traz uma reflex&#227;o sobre sua indica&#231;&#227;o para pacientes com BRE e BAV primeiro grau, onde estudos prospectivos como o PROMOTE ( <italic>clinicaltrials.org. NCT: 04139616)</italic> ir&#227;o avaliar algoritmos espec&#237;ficos de manejo dos dist&#250;rbios de condu&#231;&#227;o ap&#243;s o TAVI. Nesses pacientes, talvez a avalia&#231;&#227;o eletrofisiol&#243;gica do sistema de condu&#231;&#227;o, mesmo no per&#237;odo periprocedimento, poder&#225; auxiliar no manejo e indica&#231;&#227;o mais precisa do MP. <sup><xref ref-type="bibr" rid="B14">14</xref></sup></p>
  </body>
  <back>
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    <fn-group>
      <fn fn-type="other">
        <p>
          <italic>Minieditorial referente ao artigo: Depend&#234;ncia de Pacing a Longo-Prazo e Preditores de Implante de Pacemaker ap&#243;s Implante Percut&#226;neo de Pr&#243;tese Valvular A&#243;rtica &#8211; 1 Ano de Seguimento</italic>
        </p>
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    </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>Conduction Disturbances Associated with Transcatheter Aortic Valve Implantation: Challenge for another 20 Years?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Pozetti</surname>
            <given-names>Antonio H&#233;lio</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-1273-1823</contrib-id>
          <name>
            <surname>Ribeiro</surname>
            <given-names>Henrique Barbosa</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2001">
            <sup>2</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1001">
        <label>1</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brazil</institution>
      </aff>
      <aff id="aff2001">
        <label>2</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Hospital Samaritano Paulista, S&#227;o Paulo, SP &#8211; Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c01001">Mailing Address: Henrique Barbosa Ribeiro &#8226; Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo &#8211; Av. Dr. En&#233;as Carvalho de Aguiar, 44. Postal Code 05403-900, Cerqueira C&#233;sar, S&#227;o Paulo, SP &#8211; Brazil E-mail: henrique.ribeiro@hc.fm.usp.br</corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <kwd>TAVI</kwd>
        <kwd>Pacemaker</kwd>
        <kwd>Conduction Disturbances</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>Transcatheter aortic valve implantation (TAVI) is a well-established procedure for treating severe aortic stenosis in elderly patients, regardless of the surgical risk.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Since its introduction two decades ago, there have been major technological advances in devices, which, combined with new implantation techniques, have brought significant reductions in periprocedural complication rates, leading to their greater adoption worldwide. However, the incidence of conduction disorders showed a modest reduction, remaining the most frequent complication after TAVI,<sup><xref ref-type="bibr" rid="B2">2</xref> - <xref ref-type="bibr" rid="B4">4</xref></sup> which contributes to the increase in hospital stay, costs and the worsening of short and long-term clinical outcomes.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> In addition, the approach to conduction disorders still varies greatly between centers, especially regarding the management of new left bundle branch block (LBBB), post-procedure advanced atrioventricular block (AVB) and previous right bundle branch block (RBBB), translated into variable rates of permanent pacemaker (PM) implantation.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Among patients who received PM after TAVI, there is also great variability regarding their dependence (ventricular pacing) at follow-up.</p>
      <p>In this journal edition, Pinto et al.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> evaluated the incidence of conduction disorders, predictors and the rate of PM dependence in a population of 340 consecutive patients undergoing TAVI.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> Conduction disorders occurred in more than 50% of post-procedure patients, with LBBB being the most frequent (32%), showing spontaneous resolution in 56% of them after 6 months. The overall PM implant rate was 18.5%, with prior RBBB being its main predictor. Among the patients who required PM, the main reasons were advanced AVB (60.3%), followed by LBBB with low-degree AVB (22%). Interestingly, there was a wide variation in the percentage of ventricular pacing among patients who received PM, being 83% in patients with advanced AVB (Advanced AVB and Mobitz Type II) and only 2% in those implanted with LBBB and low-degree AVB (first-degree AVB and Mobitz type I).<sup><xref ref-type="bibr" rid="B2">2</xref> - <xref ref-type="bibr" rid="B4">4</xref></sup> However, some aspects of this study deserve reflection.</p>
      <p>First, pre-procedure assessment is essential to identify risk factors for conduction disorders and assist the operator&#8217;s strategy. As demonstrated by Pinto et al.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> the presence of previous RBBB (~10% of patients)<sup><xref ref-type="bibr" rid="B8">8</xref></sup> is the main risk factor for PM implantation after TAVI, increasing its incidence by 3 to 4 times,<sup><xref ref-type="bibr" rid="B8">8</xref></sup> it is also a predictor of post-procedure mortality.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> In the present study, previous LBBB and first-degree AVB were not correlated with a greater need for PM, unlike other authors who, in a larger number of patients, have shown that LBBB can have an impact on the need for PM in the first 30 days, but not in the follow-up after 30 days, despite no impact on mortality.<sup><xref ref-type="bibr" rid="B8">8</xref></sup></p>
      <p>A second important aspect is a procedure in which some modifiable aspects can also influence the rates of conduction disorders. For example, half of the conduction disturbances occur before valve implantation, mainly during predilation, suggesting some correlation with balloon valvuloplasty,<sup><xref ref-type="bibr" rid="B11">11</xref></sup> as also evidenced in the present study. In addition, new generation valves and techniques for higher implantantion in the annulus have significantly reduced PM rates to &lt;10%.<sup><xref ref-type="bibr" rid="B7">7</xref> , <xref ref-type="bibr" rid="B8">8</xref> , <xref ref-type="bibr" rid="B12">12</xref></sup> In fact, Pinto et al.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> showed a reduction of almost 50% with new generation prostheses and in the presence of dysfunctional surgical bioprosthesis (valve-in-valve).<sup><xref ref-type="bibr" rid="B13">13</xref></sup></p>
      <p>At the end of the procedure, a 12-lead electrocardiogram (ECG) should be performed to determine the management of any conduction disturbances and continuous monitoring for 12-24 hours.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> As seen by Pinto et al.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> the main conduction disorder is LBBB, with 10-15% progressing to PM in the first year,<sup><xref ref-type="bibr" rid="B9">9</xref></sup> reinforcing the importance of outpatient monitoring of these cases. Therefore, serial ECG evaluation is recommended, and in cases of increased PR or QRS intervals &gt; 20 ms, especially in the presence of PR&gt;240ms and QRS&gt;150ms, prophylactic PM implantation may be indicated by the risk of sudden death and advanced AVB.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> In the study by Pinto et al.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> 22% of the PM indications were for LBBB combined with first-degree AVB. However, this group had only 2% of ventricular pacing at one year, demonstrating the difficulty in managing this type of patient as well as the real need for a PM in certain circumstances since, despite low stimulation, it has occurred during paroxysmal episodes of advanced AVB or extreme bradycardia that are life-threatening.</p>
      <p>Despite two decades of technological advancement and improvement in TAVI results, conduction disturbances remain the most frequent complication. Several studies in recent years have contributed to identify risk factors, allowing a reduction in PM rates and has helped in the management of these patients. Although the study by Pinto et al.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> presents some limitations (retrospective, observational and unicentric), it reinforces previous RBBB as the main risk factor for the need of PM, and it brings a reflection on its indication for patients with LBBB and first-degree AVB, where prospective studies such as PROMOTE (clinicaltrials. org. <italic>NCT: 04139616)</italic> will evaluate specific algorithms for the management of conduction disorders after TAVI. In such patients, perhaps the electrophysiological assessment of the conduction system, even in the periprocedural period, may help in the management and the more precise indication of PM.<sup><xref ref-type="bibr" rid="B14">14</xref></sup></p>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other">
          <p>
            <italic>Short Editorial related to the article: Long-Term Ventricular Pacing Dependency and Pacemaker Implantation Predictors after Transcatheter Aortic Valve Replacement &#8211; A 1-Year Follow-Up</italic>
          </p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
