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  <front>
    <journal-meta>
      <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-loc>S&#227;o Paulo, SP, Brazil</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">Q74HSKRxLFFDYJh797ZgCBC</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2012001400001</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(12)09900501</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2012001400001</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Editorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Oclus&#227;o percut&#226;nea do ap&#234;ndice atrial esquerdo: colocando o ap&#234;ndice mais letal do corpo humano atr&#225;s das grades</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Caixeta</surname>
            <given-names>Adriano</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Silva</surname>
            <given-names>Erlon O. de Abreu</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>G&#233;n&#233;reux</surname>
            <given-names>Philippe</given-names>
          </name>
          <xref ref-type="aff" rid="aff03"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">S&#227;o Paulo</named-content>
        </addr-line>
        <institution content-type="orgname">Hospital Israelita Albert Einstein</institution>
        <country country="BR">Brazil</country>
      </aff>
      <aff id="aff02">
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">S&#227;o Paulo</named-content>
        </addr-line>
        <institution content-type="orgname">Universidade Federal de S&#227;o Paulo</institution>
        <institution content-type="orgdiv1">Escola Paulista de Medicina </institution>
        <country country="BR">Brazil</country>
      </aff>
      <aff id="aff03">
        <addr-line>
          <named-content content-type="city">New York</named-content>
          <named-content content-type="state">NY</named-content>
        </addr-line>
        <institution content-type="orgname">Cardiovascular Research Foundation</institution>
        <country country="US">USA</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>11</month>
        <year>2012</year>
      </pub-date>
      <volume>99</volume>
      <issue>5</issue>
      <fpage>968</fpage>
      <lpage>970</lpage>
      <history>
        <date date-type="received">
          <day>18</day>
          <month>10</month>
          <year>2012</year>
        </date>
        <date date-type="accepted">
          <day>18</day>
          <month>10</month>
          <year>2012</year>
        </date>
        <date date-type="rev-recd">
          <day>18</day>
          <month>10</month>
          <year>2012</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/" xml:lang="en">
          <license-p>This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.</license-p>
        </license>
      </permissions>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Ap&#234;ndice Atrial</kwd>
        <kwd>Fibrila&#231;&#227;o Atrial</kwd>
        <kwd>Anticoagulantes</kwd>
        <kwd>Cateterismo Card&#237;aco</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>22</day>
        <month>11</month>
        <year>2012</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>EDITORIAL</bold>
    </p>
    <p>Oclus&#227;o percut&#226;nea do ap&#234;ndice atrial esquerdo: colocando o ap&#234;ndice mais letal do corpo humano atr&#225;s das grades</p>
    <p>
      <bold>Adriano Caixeta<sup>I,II</sup>; Erlon O. de Abreu Silva<sup>II</sup>; Philippe G&#233;n&#233;reux<sup>III</sup></bold>
    </p>
    <p><sup>I</sup>Hospital Israelita Albert Einstein, S&#227;o Paulo, SP - Brasil </p>
    <p><sup>II</sup>Escola Paulista de Medicina, Universidade Federal de S&#227;o Paulo, S&#227;o Paulo, SP - Brasil </p>
    <p><sup>III</sup>Columbia University Medical Center and the Cardiovascular Research Foundation, New York, NY - USA</p>
    <p>
      <xref ref-type="corresp" rid="end">Correspond&#234;ncia</xref>
    </p>
    <p><bold>Palavras-chave: </bold>Ap&#234;ndice Atrial / fisiopatologia; Fibrila&#231;&#227;o Atrial / complica&#231;&#245;es; Anticoagulantes / uso terap&#234;utico; Cateterismo Card&#237;aco.</p>
    <p>A fibrila&#231;&#227;o atrial (FA) &#233; a arritmia card&#237;aca sustentada mais comum, que afeta milh&#245;es de pessoas no mundo inteiro. Tendo em vista que a FA afeta especialmente os idosos, sua preval&#234;ncia dever&#225; aumentar com o envelhecimento da popula&#231;&#227;o. S&#243; nos Estados Unidos, mais de 15 milh&#245;es de pessoas ter&#227;o FA at&#233; o ano de 2050<sup>1</sup>. Entre as suas diversas consequ&#234;ncias, a mais significativa em termos de morbidade &#233; o acidente vascular cerebral emb&#243;lico. A taxa de acidente vascular cerebral isqu&#234;mico em pacientes com FA n&#227;o valvar gira em torno de 5% ao ano, um aumento de cinco vezes em compara&#231;&#227;o com a de pessoas sem FA<sup>2</sup>. O risco de acidente vascular cerebral aumenta com a idade; o risco anual de acidente vascular cerebral atribu&#237;do &#224; FA &#233; de 1,5% em indiv&#237;duos com idade entre 50 e 59 anos, e de 23% naqueles com idade entre 80 e 89 anos. &#201; importante ressaltar que o Ap&#234;ndice Atrial Esquerdo (AAE) &#233; o principal local de forma&#231;&#227;o de trombo como precursor para o acidente vascular cerebral emb&#243;lico em pacientes com FA n&#227;o valvar<sup>1</sup>. Nesses pacientes, a anticoagula&#231;&#227;o com warfarina tornou-se o tratamento cl&#237;nico padr&#227;o, reduzindo o risco de acidente vascular cerebral em aproximadamente 60%. No entanto, o uso prolongado da warfarina implica diversos inconvenientes e complica&#231;&#245;es, incluindo a n&#227;o toler&#226;ncia, a n&#227;o ades&#227;o, intera&#231;&#245;es alimentares e medicamentosas, janela terapeutica muito limitada e aumento do risco de hemorragias<sup>3</sup>. Al&#233;m disso, a anticoagula&#231;&#227;o oral &#233; contraindicada em at&#233; 40% dos pacientes com FA, que correm risco de ter acidente vascular cerebral. Sendo assim, diversas t&#233;cnicas cir&#250;rgicas e percut&#226;neas de oclus&#227;o do AAE foram exploradas para a preven&#231;&#227;o do acidente vascular cerebral. Como alternativa para a oclus&#227;o cir&#250;rgica, a oclus&#227;o percut&#226;nea transcateter do AAE (OAAE) representa uma nova t&#233;cnica para evitar acidentes vasculares cerebrais em pacientes com alto risco de FA n&#227;o valvar e contraindica&#231;&#245;es para a terapia anticoagulante oral de longo prazo. Em pacientes selecionados, dispositivos dedicados &#224; OAAE como o Watchman (Atritech Inc, Plymouth, Minnesota) e o plug card&#237;aco Amplatzer (PCA; AGA Medical Corporation, Minneapolis, MN, EUA) t&#234;m mostrado resultados iniciais promissores. Por exemplo, o ensaio <italic>Watchman Left Atrial Appendage System for Embolic Protection in Patients With AF</italic> [Sistema de Ap&#234;ndice Atrial Esquerdo Watchman para Prote&#231;&#227;o Emb&#243;lica em Pacientes com FA (PROTECT AF)] &#150; &#250;nico estudo randomizado que discute essa t&#233;cnica &#150; mostrou a n&#227;o inferioridade da OAAE quando usada como alternativa ao uso prolongado da warfarina na preven&#231;&#227;o do acidente vascular cerebral (com menos hemorragias intracranianas) em pacientes com escore CHADS<sub>2</sub><underline>&gt;</underline> 1<sup>4</sup>. Os eventos descritos no grupo Watchman ocorreram logo no in&#237;cio do estudo e relacionavam-se ao procedimento, predominantemente derrame peric&#225;rdico e acidente vascular cerebral relacionados a embolia a&#233;rea. </p>
    <p>Al&#233;m dos crit&#233;rios cl&#237;nicos mencionados aqui no que se refere &#224; OAAE percut&#226;nea e &#224; avalia&#231;&#227;o de risco de acidente vascular cerebral pelos escores CHA<sub>2</sub>DS<sub>2</sub>-VASc, as caracter&#237;sticas anat&#244;micas da AAE devem ser levadas em considera&#231;&#227;o na sele&#231;&#227;o de candidatos para esse procedimento. O ap&#234;ndice atrial esquerdo &#233; uma estrutura longa, tubular e em forma de gancho, que apresenta um entroncamento estreito com o componente venoso do &#225;trio. Em adultos, o volume m&#233;dio do AAE &#233; de cerca de 5,2 mL, com di&#226;metros de orif&#237;cio que variam de 5 a 40 mm. Existe uma variabilidade interindividual consider&#225;vel no tamanho e na forma do AAE. As fun&#231;&#245;es do AAE incluem modula&#231;&#227;o do t&#244;nus simp&#225;tico e parassimp&#225;tico, descompress&#227;o do &#225;trio esquerdo no cen&#225;rio de press&#227;o atrial elevada e sobrecarga de volume, produ&#231;&#227;o de pept&#237;deos natriur&#233;ticos (pept&#237;deo natriur&#233;tico atrial, pept&#237;deo natriur&#233;tico cerebral) e contribui&#231;&#227;o para o enchimento diast&#243;lico do ventr&#237;culo esquerdo<sup>5</sup>. Em geral, os crit&#233;rios de inclus&#227;o para a OAAE s&#227;o: 1) aus&#234;ncia de trombo intracard&#237;aco ou ecocontraste espont&#226;neo denso pelo ecocardiograma transesof&#225;gico; 2) qualquer anatomia adversa, como AAE com m&#250;ltiplos lobos; e 3) di&#226;metro do &#243;stio do AAE &gt; 17 mm e &lt; 28 mm (32 mm para o dispositivo Watchman) e comprimento do AAE &gt; 20 mm; dimens&#245;es adequadas para acomodar a pr&#243;tese. O AAE com m&#250;ltiplos lobos e a variabilidade geom&#233;trica do &#243;stio podem resultar na veda&#231;&#227;o incompleta do ap&#234;ndice. </p>
    <p>No maior estudo observacional unic&#234;ntrico conduzido por Gu&#233;rios e cols.<sup>6</sup>, os autores relatam os resultados de curto e m&#233;dio prazo da OAAE utilizando o plug card&#237;aco Amplatzer. O estudo, que incluiu 86 pacientes com escore de risco CHADS<sub>2</sub> elevado previsto em 2,6%, demonstrou alto n&#237;vel de sucesso do procedimento (99%) com baixa taxa de complica&#231;&#245;es agudas ou subagudas, incluindo dois eventos cerebrovasculares. Vale notar que houve taxa de 97% da OAAE completa por ecocardiograma 3 a 6 meses ap&#243;s o procedimento, sem acidentes vasculares cerebrais, derrames ou emboliza&#231;&#227;o tardia do dispositivo. A taxa global de complica&#231;&#245;es descrita no estudo foi menor do que em registros menores anteriores, bem como no estudo PROTECT-AF ou na Multicentric European Experience<sup>4,7</sup>. Vale ressaltar que a maioria dos pacientes do estudo de Gu&#233;rios e cols.<sup>6</sup> (55,8%) foi submetida a procedimentos concomitantes, juntamente com a OAAE (Exemplo: implante percut&#226;neo de valva a&#243;rtica, interven&#231;&#227;o coronariana percut&#226;nea, forame oval patente ou fechamento da comunica&#231;&#227;o interatrial) &#151; considerados crit&#233;rios de exclus&#227;o no ensaio PROTECT AF. Os autores relatam ainda a viabilidade e seguran&#231;a da pr&#225;tica de realizar o procedimento guiado apenas por angiografia. O mais importante, embora se trate de um estudo observacional e n&#227;o haja compara&#231;&#227;o direta com a anticoagula&#231;&#227;o oral, &#233; que nessa coorte n&#227;o foram observados eventos durante o seguimento contra uma taxa estimada de 5,2% de eventos emb&#243;licos/ano pelo escore CHADS<sub>2</sub>.</p>
    <p>O desafio de selecionar pacientes para a OAAE percut&#226;nea depende de quatro fatores principais: 1) H&#225; uma falta de equil&#237;brio ao comparar a OAAE <italic>vs</italic>. terapia cl&#237;nica em pacientes com contraindica&#231;&#245;es para a anticoagula&#231;&#227;o oral. Por raz&#245;es &#233;ticas, essa compara&#231;&#227;o direta n&#227;o pode ser realizada. Assim, uma vez que n&#227;o h&#225; uma op&#231;&#227;o alternativa para evitar acidentes vasculares cerebrais emb&#243;licos, os pacientes contraindicados para anticoagulantes parecem ser os candidatos ideais para a OAAE; 2) Por outro lado, em pacientes eleg&#237;veis para a anticoagula&#231;&#227;o oral, h&#225; escassez de dados que comparem as duas estrat&#233;gias. Como mencionado anteriormente, o estudo PROTECT AF<sup>4</sup> &#233; o &#250;nico estudo randomizado, at&#233; ent&#227;o, que comparou a anticoagula&#231;&#227;o oral <italic>vs</italic>. OAAE. O estudo demonstrou n&#227;o inferioridade no que se refere ao desfecho prim&#225;rio, embora tenha sido demonstrado maior risco de complica&#231;&#245;es dos procedimentos, resultado com maior probabilidade de vi&#233;s devido &#224; curva de aprendizagem inicial. Tal como acontece com todos os novos procedimentos de interven&#231;&#227;o, no entanto, tem-se observado uma melhoria significativa na seguran&#231;a da OAAE de acordo com maior experi&#234;ncia<sup>8</sup> dos operadores e desenvolvimento dos dispositivos, fen&#244;meno demonstrado anteriormente e corroborado por Gu&#233;rios e cols.<sup>6</sup> Novos estudos controlados randomizados com maior tempo de seguimento que comparem novos procedimentos de OAAE (como com o plug card&#237;aco Amplatzer) com anticoagula&#231;&#227;o oral ser&#227;o necess&#225;rios para investigar o impacto da OAAE sobre esses pacientes de menor risco (isto &#233;, pacientes eleg&#237;veis para o anticoagulante oral). Al&#233;m disso, a fun&#231;&#227;o desses dispositivos em pacientes de menor risco na era de anticoagulantes rec&#233;m-desenvolvidos, que incluem o uso dos inibidores do fator Xa apixaban e rivaroxabana, e o inibidor direto da trombina, o dabigatran, tamb&#233;m deve ser determinada em ensaios cl&#237;nicos randomizados. Embora a ades&#227;o possa ser maior com esses novos anticoagulantes e o risco de complica&#231;&#245;es hemorr&#225;gicas pode ser bastante reduzido quando comparado com a warfarina, ainda h&#225; grande risco de hemorragia com o passar do tempo<sup>9</sup>. Diretrizes para abordagens n&#227;o farmacol&#243;gicas para a preven&#231;&#227;o do tromboembolismo, como a OAAE percut&#226;nea, aguardam os resultados de outros estudos em andamento. No momento, a indica&#231;&#227;o para o procedimento deve ser individualizada ap&#243;s uma avalia&#231;&#227;o cuidadosa do risco global do paciente, que inclui o equil&#237;brio entre o risco de acidente vascular cerebral e hemorragia; 3) A OAAE pode contribuir para a redu&#231;&#227;o do risco de tromboembolismo, mas isso pode resultar em sequelas fisiol&#243;gicas indesej&#225;veis, tais como a redu&#231;&#227;o da complac&#234;ncia atrial e diminui&#231;&#227;o da capacidade de secre&#231;&#227;o do fator natriur&#233;tico atrial em resposta &#224; press&#227;o e a sobrecarga de volume. No entanto, essas consequ&#234;ncias fisiol&#243;gicas ainda s&#227;o desconhecidas; E, por fim, 4) O custo-efic&#225;cia do procedimento deve ser explorado em estudos futuros, onde se ponderaria o custo inicial substancial do dispositivo contra o custo total da terapia de anticoagula&#231;&#227;o oral de longo prazo. </p>
    <p>Em conclus&#227;o, a OAAE &#233; uma alternativa aceit&#225;vel em pacientes selecionados e de alto risco portadores de FA e que s&#227;o candidatos sub-&#243;timos - ou com contra-indica&#231;&#227;o - a terapia anticoagulante oral. Outrora considerado "o ap&#234;ndice mais letal do corpo humano", o AAE pode atualmente ser percut&#226;neamente exclu&#237;do, isolado, encarcerado e condenado a pris&#227;o perp&#233;tua por causar acidentes vasculares cerebrais emb&#243;licos.</p>
    <p>
      <fn id="end" fn-type="corresp">
        <p>Correspond&#234;ncia:</p>
        <p> Adriano Caixeta </p>
        <p> Av. Dom Armando Lombardi, 819, Apto. 21B, Vila Progredior </p>
        <p> CEP 05616-011, Sao Paulo, SP &#150; Brasil </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="adriano.caixeta@einstein.br">adriano.caixeta@einstein.br</email>
        </p>
      </fn>
    </p>
    <p>Artigo recebido em 18/10/2012; revisado em 18/10/2012; aceito em 18/10/2012.</p>
  </body>
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  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Editorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Percutaneous left atrial appendage occlusion: putting the most lethal human attachment behind bars</article-title>
      </title-group>
      <kwd-group xml:lang="en">
        <kwd>Atrial Appendage</kwd>
        <kwd>Atrial Fibrillation</kwd>
        <kwd>Anticoagulants</kwd>
        <kwd>Heart Catheterization</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>EDITORIAL</bold>
      </p>
      <p><undefined id="tx-body2"/>Percutaneous left atrial appendage occlusion: putting the most lethal human attachment behind bars</p>
      <p>
        <bold>Adriano Caixeta<sup>I,II</sup>; Erlon O. de Abreu Silva<sup>II</sup>; Philippe G&#233;n&#233;reux<sup>III</sup></bold>
      </p>
      <p><sup>I</sup>Hospital Israelita Albert Einstein, S&#227;o Paulo, SP - Brazil</p>
      <p><sup>II</sup>Escola Paulista de Medicina, Universidade Federal de S&#227;o Paulo, S&#227;o Paulo, SP - Brazil</p>
      <p><sup>III</sup>Columbia University Medical Center and the Cardiovascular Research Foundation, New York, NY - USA</p>
      <p>Mailing Address</p>
      <p><bold>Keywords: </bold>Atrial Appendage / physiopathology; Atrial Fibrillation / complications; Anticoagulants / therapeutic use; Heart Catheterization.</p>
      <p>Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting millions of people worldwide. Since AF mainly affects the elderly, its prevalence is expected to increase with the aging of the population. In the United States alone, over 15 million people will have AF by the year 2050<sup>1</sup>. Among its many consequences, the one that carries the greatest burden with regard to morbidity is embolic stroke. The rate of ischemic stroke among patients with nonvalvular AF averages 5% per year, a fivefold increase compared with that of people without AF<sup>2</sup>. The risk of stroke increases with age. The annual risk of stroke attributed to AF is 1.5% in subjects aged 50 to 59 years and 23% in those aged 80 to 89 years. Importantly, the left atrial appendage (LAA) is the primary site of thrombus formation as a precursor to embolic stroke in nonvalvular AF patients<sup>1</sup>. In these patients, anticoagulation with warfarin has become standard medical therapy, reducing the risk of stroke by ~60%. Nonetheless, the long-term use of warfarin carries several drawbacks and complications, including non-tolerance, non-adherence, interactions with food and other medications, a very narrow therapeutic range, and an increased risk of bleeding<sup>3</sup>. In addition, oral anticoagulation is contraindicated in up to 40% of patients with AF who are at risk for stroke. Accordingly, several surgical and percutaneous techniques have been explored to occlude the LAA for stroke prevention. As an alternative to surgical closure, percutaneous transcatheter LAA closure (LAAC) represents a novel approach to prevent strokes in high-risk patients with nonvalvular AF and contraindications to long-term oral anticoagulant therapy. In selected patients, dedicated LAAC devices such as Watchman (Atritech Inc, Plymouth, Minn) and the Amplatzer cardiac plug (ACP; AGA Medical Corp., Minneapolis, MN, USA) have shown encouraging initial results. For instance, The Watchman Left Atrial Appendage System for Embolic Protection in Patients With AF (PROTECT AF) trial &#150; the only randomized study to address this issue &#150; has shown the therapeutic noninferiority of LAAC when used as an alternative to long-term warfarin in preventing stroke (with less intracranial hemorrhages) in patients with a CHADS<sub>2</sub> score <underline>&gt;</underline>1<sup>4</sup>. The events in the Watchman group occurred early and were related to the procedure, predominantly pericardial effusion and procedural stroke related to air embolism. </p>
      <p>Besides the aforementioned clinical criteria for percutaneous LAAC and the assessment of stroke risk by CHADS<sub>2</sub> and the CHA<sub>2</sub>DS<sub>2</sub>-VASc scores, anatomical characteristics of the LAA should be taken into account when selecting candidates for this procedure. The left atrial appendage is a long, tubular and hooked structure which has a narrow junction with the venous component of the atrium. In adults, the mean volume of the LAA is approximately 5.2 ml, with orifice diameters ranging from 5 to 40 mm. There is considerable inter-individual variability in the size and shape of the LAA. Functions of the LAA include modulation of sympathetic and parasympathetic tone, decompression of the left atrium in the setting of elevated atrial pressure and volume overload, production of natriuretic peptides (atrial natriuretic peptide, brain natriuretic peptide) and contribution to the diastolic filling of the left ventricle<sup>5</sup>. In general, the inclusion criteria for LAAC consist of: 1) absence of intracardiac thrombus or dense spontaneous echo contrast by transesophageal echocardiogram; 2) any adverse anatomy such as multiple LAA lobes; and 3) LAA ostium diameter &gt; 17 mm and &lt; 28 mm (32 mm for Watchman device) and LAA length &gt; 20 mm; dimensions suitable to accommodate the prosthesis. Multilobular LAA and ostium geometric variability may result in an incomplete seal of the appendage. </p>
      <p>In the largest single center observational study of the subject by Gu&#233;rios et al.<sup>6</sup>, the authors report the short- and mid-term results of LAAC using the Amplatzer cardiac plug. The study, which included 86 patients with a high predicted risk score of 2.6% by CHADS<sub>2</sub>, demonstrated high procedural success (99%) with a low rate of acute or subacute complications, including 2 cerebrovascular events. Of note, there was a high 97% rate of complete LAAC by echocardiogram 3 to 6 months after the procedure with no strokes or late device embolization. The overall rate of complications in this report was lower than in previous smaller registries as well as in the PROTECT-AF trial or the Multicentric European Experience<sup>4,7</sup>. It is noteworthy that most patients in the study by Gu&#233;rios et al<sup>7</sup> (55.8%) underwent concomitant procedures along with LAAC (e.g., transcatheter aortic valve implantation, percutaneous coronary intervention, patent foramen ovale or atrial septal defect closure) &#151; that were once considered exclusion criteria in the PROTECT AF trial. The authors also report the feasibility and safety of the elegant practice of performing the procedure guided by angiography alone. Most importantly, although it is an observational study and there is no direct comparison with oral anticoagulation, no events in this cohort were observed during follow-up against an estimated rate of 5.2% embolic events/year by CHADS<sub>2</sub> score.</p>
      <p>The challenge of selecting patients for percutaneous LAAC relies on 4 main factors: 1) there is a lack of equipoise when comparing LAAC vs. medical therapy in patients with contraindications to oral anticoagulation. For ethical reasons, such a head-to-head comparison cannot be conducted. Thus, since there is no alternative option to prevent embolic strokes, patients who are contraindicated for anticoagulants seem to be the ideal candidates for LAAC; 2) conversely, in patients eligible for oral anticoagulation, there is a paucity of data comparing the 2 strategies; as mentioned before, PROTECT AF<sup>4</sup> is the only randomized trial thus far comparing LAAC vs. oral anticoagulation. The trial demonstrated noninferiority with regard to the primary endpoint, although a higher risk of procedural complications was shown, a finding most likely biased by the initial learning curve. As with all new interventional procedures, however, there has been a significant improvement in the safety of LAAC with increased operator experience<sup>8 </sup>and device development, a phenomenon previously demonstrated and corroborated by Gu&#233;rios et al<sup>6</sup>. Further randomized controlled trials with longer follow-up comparing novel LAAC procedures (such as with the Amplatzer Cardiac Plug) with oral anticoagulation are required to investigate the impact of LAAC on these lower risk patients (i.e., patients eligible for oral anticoagulant). Furthermore, the role of these devices in lower risk patients in the era of novel anticoagulants, including the use of oral factor Xa inhibitors apixaban and rivaroxaban, and the direct thrombin inhibitor dabigatran, should also be determined in further randomized controlled trials. Although compliance may improve with these novel anticoagulants and the risk of bleeding complications can be somewhat reduced compared with warfarin, there is still an increased risk of bleeding over time<sup>9</sup>. Guidelines for non-pharmacological approaches to prevention of thromboembolism such as percutaneous LAAC are pending the results of additional ongoing trials. At present, the indication for the procedure must be individualized after a thorough evaluation of the patient's global risk, which includes balancing the risk of stroke and bleeding; 3) LAAC may contribute to a reduction in the risk of thromboembolism, but this may result in undesirable physiological sequelae such as reduced atrial compliance and a decreased capacity for atrial natriuretic factor secretion in response to pressure and volume overload. Nonetheless, these physiological consequences are still unknown; and, finally 4) the cost-effectiveness of the procedure must be explored in future studies, weighing the initial substantial cost of the device against the total cost of long-term oral anticoagulation therapy. </p>
      <p>In conclusion, LAAC is an acceptable therapeutic option in selected high-risk patients with non-valvular AF who are suboptimal candidates &#150; or not candidates at all &#150; for oral anticoagulant therapy. Once deemed "our most lethal human attachment" in AF patients<sup>10</sup>, the LAA can now be safely and efficaciously excluded, isolated, and imprisoned percutaneously with a life sentence for causing embolic strokes.</p>
      <p>
        <bold>References</bold>
      </p>
    </body>
  </sub-article>
</article>
