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. 2021 Feb 19;116(2):334–345. [Article in Portuguese] doi: 10.36660/abc.20200477
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Fibrilação Atrial (Parte 2) – Ablação por Cateter

Eduardo B Saad 1,2, Andre d’Avila 3,4
PMCID: PMC7909976  PMID: 33656085

Resumo

Após mais de 20 anos desde sua utilização inicial, a ablação por cateter se tornou um procedimento rotineiramente realizado para tratamento de pacientes com fibrilação atrial (FA). Fundamentado inicialmente no isolamento elétrico das veias pulmonares em pacientes com FA paroxística, subsequentes avanços no entendimento da fisiopatologia levaram a técnicas adicionais não só para obter melhores resultados, mas também para tratar pacientes com formas persistentes de arritmia, assim como pacientes com cardiopatia estrutural e insuficiência cardíaca.

Keywords: Arritmias Cardíacas, Fibrilação Atrial/terapia, Ablação por Cateter/métodos, Ecocardiografia/métodos


Significativos avanços tecnológicos, em especial no mapeamento eletroanatômico 3D, no uso de ecocardiograma intracardíaco e na forma de energia aplicada (crioablação e força de contato tecidual com radiofrequência), permitiram redução significativa na taxa de complicações e no uso de radiação ionizante.

Atualmente, a ablação é o tratamento mais eficiente para pacientes com FA, sendo uma excelente alternativa ao uso de fármacos antiarrítmicos, cujo desenvolvimento foi insignificante nas últimas décadas.

Com as pioneiras observações feitas por Haissaguerre et al.,1 demostrou-se o papel fundamental de focos arritmogênicos nas veias pulmonares (VP) na fisiopatologia da iniciação e na manutenção dos episódios de FA. Nestas foi estabelecido o conceito de FA focal, em que uma arritmia atrial que acomete difusamente ambos os átrios tem origem bem determinada, logo, passível de intervenções terapêuticas. Técnicas utilizando a ablação por cateter foram desenvolvidas e aperfeiçoadas, visando à eliminação dos focos geradores da FA por meio da ablação circunferencial ao redor das VP,2 - 4 com índices de sucesso e performance superiores quando comparados com a melhor terapêutica farmacológica.5 - 10

O objetivo deste artigo é revisar os avanços ocorridos no tratamento ablativo da FA e descrever para o cardiologista clínico o atual estado da arte em relação a suas indicações, técnicas, resultados e complicações.

Estratégias de ablação

Ao longo dos últimos 20 anos, diversas estratégias de ablação foram utilizadas para controle da FA. Em comum, é consenso atual que o isolamento de todas as VP é fundamental em todos os grupos de pacientes (FA paroxística, persistente ou persistente de longa duração).11 - 15 Esse isolamento deve ser comprovado eletricamente por mapeamento circular no interior das VP (Figuras 1 e 2), pois essa etapa é primordial para o sucesso do procedimento. Estudos recentes mostram que deve, inclusive, ser realizado sem interrupção da anticoagulação oral, estratégia que reduz os riscos trombóticos e hemorrágicos.16 - 18

Em pacientes com FA paroxística, em geral, o isolamento das VP é tudo que é necessário, realizando-se lesões adicionais apenas em situações específicas (p. ex., focos deflagradores mapeados fora das VP). Alguns centros realizam de rotina o isolamento da veia cava superior,19 , 20 visto que também pode ser, mais raramente, fonte deflagradora de ectopias e arritmias , podendo induzir FA. A maioria das publicações demonstra resultados favoráveis, com taxas de sucesso superiores a 70%.6 , 7 , 9

O isolamento das VP pode ser realizado utilizando: 1) energia de radiofrequência (RF), por meio de aplicações focais ponto a ponto (Figura 1A), idealmente com cateteres com sensores da pressão tecidual exercida ( Figura 1 B), ou 2) congelamento (crioablação), utilizando um cateter-balão posicionado no antro das VP, capaz de realizar toda a lesão tecidual simultaneamente na circunferência em contato com o tecido (Figura 1D). Estudo randomizado (Fire and ICE)21 comparando diretamente as duas estratégias para tratamento de FA paroxística demonstrou resultados semelhantes. Esses achados foram replicados em um segundo estudo randomizado (CIRCA-DOSE)22 que comparou dois regimes de crioablação (4min vs . 2min de congelamento) ao uso da RF com força de contato para isolamento das VP em pacientes com FA paroxística. Nesse estudo, observou-se redução da carga de FA >98% por meio de monitoramento eletrocardiográfico contínuo. Importante salientar que o cateter-balão usualmente não é utilizado para ablação em outras regiões além das VP; quando necessário, deve-se utilizar um cateter de RF (Figura 1C).

Figura 1. Ablação por cateter para tratamento da FA paroxística. A) Isolamento das VP esquerdas por ablação circunferencial (RF ponto a ponto) guiado por mapeamento eletroanatômico 3D (sistema NAVx – Abbott), demonstrando o desaparecimento dos eletrogramas (*) registrados por um cateter circular no interior das VP. B) Isolamento das VP direitas (sistema CARTO – Biosense Webster) com cateter com sensor de contato tecidual (demonstrado pelo vetor de força e pela quantificação = 7g); o cateter circular de mapeamento está no interior da VP superior direita. C) Ablação de FA persistente (sistema NAVx – Abbott) demonstrando a extensão das lesões de RF para isolamento da parede posterior do AE (lesão linear no teto e na parte inferior), levando ao desaparecimento dos eletrogramas na parede posterior (registrados pelo cateter circular de mapeamento). D) Imagem fluoroscópica durante crioablação para isolamento da VP superior esquerda, demonstrando o cateter-balão (seta) insuflado e em contato com o óstio dessa veia. A ablação em toda a circunferência da VP é realizada simultaneamente pelo balão, que usualmente é restrito para isolamento das VP – quando necessário ablação adicional, um cateter de RF deve ser utilizado.

Figura 1

Já nas formas persistente e persistente de longa duração, a criação de barreiras elétricas adicionas é frequentemente realizada, visto que o simples isolamento das VP é insuficiente e associado a altas taxas de recorrência.23 - 25 Diversas estratégias foram estudadas,26 - 37 sendo as mais frequentemente utilizadas: ablação de deflagradores fora das veias pulmonares, lesões lineares no átrio esquerdo (AE) e extensas aplicações de RF em sítios com registro de eletrogramas fracionados durante a FA (mais comumente observados na parede posterior, septo, teto, anel mitral, base do apêndice atrial esquerdo (AAE) e no interior do seio coronário). Durante a aplicação de RF nesses locais, pode ocorrer reversão a taquicardias atriais regulares ou até mesmo ao ritmo sinusal.

Merece ressalva o resultado negativo do estudo randomizado Star AF II,38 que comparou a adição de lesões lineares e ablação de potenciais fragmentados ao isolamento das VP em pacientes com FA persistente. Nesse estudo, não houve diferença na manutenção do ritmo sinusal aos 18 meses entre os grupos (59% para o isolamento apenas vs. 49% e 46% nos outros grupos, sem significância estatística). Por isso, muitos centros ainda praticam apenas o isolamento das VP mesmo em pacientes com FA persistente.

Uma estratégia mais agressiva para eliminação de deflagradores foi também testada em um estudo randomizado controlado (BELIEF Trial)39 – o isolamento elétrico do AAE. Neste, o isolamento dessa estrutura em adição à ablação convencional foi associado à redução de 55% no risco relativo de recorrência de FA em uma população de pacientes com FA persistente de longa duração . O isolamento do AAE é atualmente realizado seletivamente devido ao fato de exigir extensas aplicações de RF e adicionar risco para fenômenos embólicos – a perda da contração do AAE leva à remora e formação de trombo. Pacientes com AAE eletricamente isolado devem ser anticoagulados cronicamente independente do escore CHADSVASC, e devem ser submetidos à oclusão dessa estrutura caso o anticoagulante seja contraindicado.40

Portanto, em formas mais persistentes de FA com significativo remodelamento atrial, há necessidade de mudança do substrato atrial, implicando maior número e extensão das aplicações de RF. Não há consenso na literatura quanto a melhor estratégia a ser utilizada ( Tabela 1 ). A evolução da FA para formas persistentes representa progressão de um processo patológico41 , 42 e deve servir de motivação para o tratamento mais precoce, quando ainda paroxística. Um grande estudo retrospectivo com mais de 4.500 pacientes analisou o impacto do tempo entre o diagnóstico de FA e a realização da ablação.43 Os resultados são contundentes, demonstrando que quanto mais cedo a ablação é realizada, melhores são os resultados – estabelecendo o “conceito oncológico da FA”, ou seja, os melhores resultados são obtidos quando se faz o tratamento nas fases iniciais da doença (isolamento das VP em pacientes com FA paroxística). Em fases mais avançadas (FA persistente e permanente), o tratamento é bem mais extenso e com resultados inferiores. Por isso, aqui também, quanto mais cedo, melhor.

Tabela 1. – Estratégias durante ablação da fibrilação atrial.

Para o isolamento elétrico das veias pulmonares
Classe I – A Isolamento das VP é recomendado para todos os procedimentos de ablação de FA
Classe I – B Demonstração de bloqueio de entrada nas VP
Classe IIa – B Monitoramento para reconexão das VP por 20 minutos após o isolamento inicial
Classe IIb – B
  • Administração de adenosina 20min após isolamento das VP

  • Estimulação ao longo da linha de ablação circunferencial

  • Demonstração do bloqueio de saída nas VP

Em conjunto com isolamento das veias pulmonares
Classe I – B Ablação do ICT em pacientes com histórico de flutter típico ou se a arritmia é indutível durante a ablação da FA
Classe I – C Se forem realizadas lesões lineares, o bloqueio bidirecional deve ser demonstrado
Classe IIa – C
  • Se forem identificados gatilhos reprodutíveis extra-VP, a ablação deve ser considerada

  • Ao usar um cateter de RF com sensor de contato, um mínimo de 5 a 10g de força é razoável

Classe IIb – B
  • O isolamento da parede posterior do AE pode ser considerado para ablação inicial ou repetida de AF persistente ou persistente de longa duração.

  • Isoproterenol em altas doses para detecção e ablação de gatilhos extra-VP pode ser considerado para procedimentos iniciais ou reintervenções para FA paroxística, persistente ou persistente de longa duração

VP: veia pulmonar; FA: fibrilação atrial; RF: radiofrequência; ICT: istmo cavotricuspídeo; AE: átrio esquerdo.

Tecnologias para guiar a ablação

Independentemente da estratégia utilizada, métodos de mapeamento por imagem frequentemente são utilizados em adição ao tradicional mapeamento eletrofisiológico. Dois tipos de tecnologia são apropriados nesta circunstância:

  1. Mapeamento eletroanatômico: esta forma de mapeamento em 3D permite definir com precisão a anatomia da cavidade atrial esquerda e das VP, delinear o substrato funcional pela medida da voltagem tecidual, marcar as lesões de RF ( Figura 1 ) no mapa formado e traduzir em cores a informação elétrica obtida. É possível, também, navegar em imagens da anatomia real originada em tomografia computadorizada ou ressonância magnética. Essa metodologia é especialmente útil para reduzir o tempo de exposição à fluoroscopia, tornando de fácil apreciação o circuito ou o foco da arritmia e as lesões realizadas para tratá-las. Dois sistemas estão atualmente disponíveis no Brasil: CARTO – Biosense Webster e NavX – Abbott Medical .

  2. Ecocardiograma intracardíaco (ICE): através de um cateter inicialmente posicionado no átrio direito, é possível obter imagens ultrassonográficas detalhadas da anatomia cardíaca em tempo real,44 , 45 permitindo uma manipulação precisa e segura dos cateteres através das diversas estruturas visualizadas ( Figura 2 ). Sua utilização permite também a realização segura das punções transeptais sob visualização direta e a detecção precoce de complicações agudas (derrame pericárdico, trombos). Estudo recente com mais de 100.000 pacientes submetidos à ablação mostra a importância desse método na significativa redução do risco de uma complicação grave – a perfuração cardíaca.46 Nessa série contemporânea, o não uso do ICE foi o maior fator de risco para perfuração (RR 4.85).

Figura 2. Uso do eco intracardíaco (ICE) durante ablação da FA. A) Desenho esquemático mostrando o cateter de ICE na cavidade atrial direita com feixe direcionado para guiar as duas punções transeptais e o posicionamento dos cateteres de mapeamento circular e de ablação no AE. B) Imagem do ICE demonstrando o posicionamento antral e o contato tecidual durante aplicação de RF ao redor da VP superior esquerda (VPSE). AE: átrio esquerdo; AAE: apêndice atrial esquerdo; Map: cateter de mapeamento; RF: cateter de ablação.

Figura 2

Essas ferramentas não fluoroscópicas têm sido cada vez mais utilizadas nos laboratórios de eletrofisiologia ao longo dos anos e podem até orientar todo o procedimento de ablação, evitando completamente o uso de raios X.47 Relatado inicialmente há aproximadamente 10 anos, as técnicas “Zero-Fluoro” estão ganhando popularidade na comunidade eletrofisiológica, porque foram demonstradas tão seguras e eficazes quanto os métodos tradicionais guiados pela fluoroscopia.48 - 50

Recorrências

Dois fatores predominantes justificam as recorrências da FA após ablação:

  1. Reconexão da condução nas VP: para que as lesões circunferenciais sejam permanentes, deve ocorrer formação de tecido fibroso, usualmente 4 a 8 semanas após a lesão aguda (edema tecidual). Caso a lesão não tenha profundidade suficiente, pode haver tecido viável remanescente após a reabsorção do edema. Basta um pequeno segmento para restabelecer a condução elétrica.

  2. Ocorrência de focos independentes, fora das VP: estes ocorrem mais frequentemente, mas não exclusivamente, em formas persistentes de FA ou em pacientes com remodelamento atrial.

A reconexão das VP é facilmente resolvida com novas aplicações de RF nos gaps de condução. A reintervenção geralmente é rápida, fácil e segura. Em FA paroxística, eleva os índices de controle da FA a 95%. Com o uso de cateteres com sensor de contato tecidual, é um fenômeno cada vez mais raro,51 - 53 pois as lesões de RF tendem a ser mais profundas e permanentes.54

Os focos extra-VP representam um substrato atrial mais difuso, sendo necessários o reconhecimento e a ablação extensa, sem os quais não é possível o controle da arritmia.33 , 54 , 55 Mais comumente, envolvem a parede posterior do AE, o AAE e o seio coronário32 , 54 – estruturas que podem ser também isoladas por aplicações de RF. É possível a manutenção do ritmo sinusal a longo prazo, mesmo se necessário mais de uma intervenção.

Seleção de pacientes e resultados

A seleção de pacientes para ablação por cateter da FA baseia-se atualmente na falência do tratamento clínico ( Tabela 2 ). De acordo com o último consenso de especialistas HRS/EHRA/ECAS/APHRS/SOLAECE, de 2017,11 a indicação primária para ablação de FA é a presença de fibrilação atrial paroxística ou persistente sintomática, refratária ou intolerante a pelo menos um fármaco antiarrítmico da classe I ou III. Há sólidas evidências de melhora em parâmetros de qualidade de vida desses pacientes.5 , 56

Tabela 2. – Indicações para ablação por cateter na fibrilação atrial.

FA sintomática, refratária ou intolerante a pelo menos 1 fármaco antiarrítmico (classe I ou III)
Classe I – A FA paroxística
Classe IIa – B FA persistente
Classe IIb – C FA persistente de longa duração
FA sintomática, antes do início de fármacos antiarrítmicos (Classe I ou III)
Classe IIa – B FA paroxística
Classe IIa – C FA persistente
Classe IIb – C FA persistente de longa duração
Indicações em populações de pacientes pouco representadas em ensaios clínicos
Classe IIa – B
  • Insuficiência cardíaca congestiva

  • Pacientes ≥75 anos de idade

  • Cardiomiopatia hipertrófica

  • Jovens (≤45 anos de idade)

  • Síndrome taqui-bradi

Classe IIa – C Atletas com FA
Classe IIb – C FA assintomática

FA: fibrilação atrial.

Esta técnica pode ser utilizada em pacientes com diversos tipos de cardiopatia (doença arterial coronária, hipertrofia ventricular esquerda, insuficiência cardíaca) e apresentações clínicas de FA (paroxística, persistente ou de longa duração), porém, os melhores resultados são obtidos nos pacientes com coração estruturalmente normal. No maior estudo randomizado que comparou ablação com tratamento farmacológico (CABANA),7 sobrevida livre de recorrência da FA é significativamente melhor (HR 0.53) nos pacientes ablacionados quando comparados aos que permanecem em uso de múltiplos fármacos antiarrítmicos. Apesar disso, nesse estudo, não foi demonstrada redução em desfechos duros combinados (morte, acidente vascular cerebral [AVC], sangramento grave ou parada cardíaca) na análise intention to treat , apesar de haver problemas com grande crossover de pacientes para o grupo ablação (27%). Nesse estudo, os subgrupos que mais se beneficiaram foram os mais jovens (<65 anos) e os pacientes com insuficiência cardíaca congestiva.

A seleção de pacientes com formas persistente e permanente de FA segue o mesmo raciocínio, porém a decisão deve ser individualizada de acordo com o tamanho do AE57(que é um importante fator preditor de recorrência) e a duração da FA. FA persistente é uma doença heterogênea, com diferentes graus de fibrose atrial e com influência do sistema nervoso autônomo e outros processos fisiopatológicos ainda mal compreendidos, o que explica os resultados heterogêneos observados com diferentes estratégias de ablação. Essa forma exige uma definição individual do substrato e mecanismos envolvidos.58 , 59

É importante notar que, mesmo com a estratégia de extensas aplicações de RF descritas, o índice de recidivas e a necessidade de novos procedimentos são maiores. Na experiência de Natale et al., 60% dos pacientes mantiveram ritmo sinusal sem fármacos após o primeiro procedimento.54 Naqueles que foram submetidos a uma segunda intervenção, 80% mantiveram ritmo sinusal. A Tabela 3 sumariza alguns dos principais estudos publicados.

Tabela 3. – Ensaios clínicos em ablação de fibrilação atrial.

Estudo (ano) Tipo Estratégia de ablação Follow -up (meses) Manutenção do ritmo sinusal p-valor
FA paroxística
Thermocool AF (2010) Randomizado ablação RF ou DAA; multicêntrico IVP CFAE e linhas opcionais 167 12 66%/16% <0,001
STOP AF (2013) Randomizado para crioablação ou DAA; multicêntrico IVP 245 12 70%/7% <0,001
SMART AF (2014) Não randomizado; cateter sensor de contato; multicêntrico IVP CFAE e linhas opcionais 172 12 72,5%/NA <0,0001
TOCCASTAR (2015) Randomizado com ou sem cateter sensor de contato; multicêntrico IVP CFAE, gatilhos e linhas extra-VP opcionais 300 12 67,8%/69,4% 0,0073*
RAAFT-2 (2014) Randomizado ablação RF ou DAA (primeira linha); multicêntrico IVP gatilhos extra-VP opcionais 127 24 45%/28% 0,02
MANTRA-PAF (2012) Randomizado ablação RF ou DAA (primeira linha); multicêntrico PVI + linha teto linhas mitral e ICT opcionais 294 24 Carga de FA: 13%/19% -
FIRE and ICE (2016) Randomizado RF ou crioablação; multicêntrico IVP 762 12 64,1% (RF)/65,4% (crio) -
CIRCA DOSE (2019) Randomizado RF ou crio 4min ou crio 2min; multicêntrico IVP 346 12 53,9% (RF)/52,2% (crio 4min)/51,7% (crio 2min) 0,87
FA persistente
TTOP (2014) Randomizado ablação RF ou DAA / CVE IVP + CFAE 210 6 56%/26% <0,001
SARA (2014) Randomizado ablação RF ou DAA; multicêntrico IVP CFAE e linhas opcionais 146 12 70%/44% 0,002
STAR AF II (2015) Randomizado 3 estratégias de ablação RF; multicêntrico IVP; IVP + CFAE; IVP + Linhas 589 18 59%/49%/46% 0,15
FA paroxística ou persistente
CABANA (2019) Randomizado ablação RF ou DAA; multicêntrico IVP ablação adicional opcional 2204 48,5 69%/50% -

FA: fibrilação atrial; RF: radiofrequência; DAA: drogas antiarrítmicas; IVP: isolamento das veias pulmonares; CFAE: eletrogramas atriais fracionados complexos; CVE: cardioversão elétrica; *não inferioridade.

A ablação por cateter é menos eficaz em determinados subgrupos de pacientes,60 em que ainda é necessário avançar no conhecimento fisiopatológico: átrios dilatados e fibrosados, FA persistente ou de longa duração, cardiomiopatia hipertrófica, infiltrado amiloide, obesidade e apneia do sono.

O acompanhamento a longo prazo de pacientes submetidos à ablação por cateter mostra que há a possibilidade de recidivas tardias,61 - 63 na ordem de 7% ao ano nos primeiros 5 anos. Deve-se destacar que a estimativa do real sucesso da ablação é dificultada pelas inconsistências e heterogeneidades nas definições de sucesso e recorrências nos diferentes estudos. Como exemplo, a maior parte dos estudos considera recidiva qualquer arritmia atrial com duração maior que 30 segundos, uma definição claramente com pouco significado clínico. Nesse cenário, a carga de FA deve ser mais valorizada nas pesquisas futuras.

Com a tendência ao isolamento permanente das VP, observa-se mais frequentemente a recorrência por aparecimento de focos extra-VP, que devem ser identificados e ablacionados.32 , 33 , 54 , 64 Portanto, é importante manter a vigilância com monitoramento periódico dos pacientes, sendo prudente manter a terapia anticoagulante nos pacientes de mais alto risco que não apresentem contraindicações.

A Tabela 4 resume os cuidados adjuvantes para maximizar a segurança e a eficácia do procedimento.

Tabela 4. – Estratégias adjuvantes à ablação de fibrilação atrial.

Não diretamente relacionado ao procedimento de ablação
Classe IIa – B
  • Perda de peso

  • Considerar o IMC do paciente na avaliação para procedimento de ablação

  • Pesquisar sinais e sintomas de apneia do sono

  • Tratar apneia do sono

Classe IIb – C
  • Interrupção de DAA antes da ablação para melhorar os resultados a longo prazo não é clara

  • Uso de DAA durante o período de cicatrização (3 meses) após a ablação para melhorar os resultados não é claro

Redução do risco durante o procedimento de ablação
Classe I – B Delineamento preciso da anatomia das VP para evitar ablação no seu interior
Classe I – C Redução da potência aplicada na parede posterior do AE, próximo ao esôfago
Classe IIa – C Utilização de um cateter com sensor de temperatura no lúmen esofágico para guiar a titulação da energia aplicada

DAA: drogas antiarrítmicas; IMC: índice de massa corporal; VP: veia pulmonar; AE: átrio esquerdo.

Situações especiais

Diretrizes internacionais publicadas em 2016 e 2017 e atualizadas em 2019 e 2020 pelas diferentes sociedades internacionais (SBC/HRS/EHRA/ECAS/APHRS/ACC/AHA/ESC/EHRA)11 - 13 , 15 recomendam de forma quase consensual o tratamento ablativo em situações especiais ( Tabela 2 ):

1) Ablação como primeira escolha:

A crescente segurança e a eficácia permitem que a ablação seja oferecida como terapia de primeira linha para tratamento (antes mesmo do uso de fármacos antiarrítmicos) em algumas situações especiais (atletas, jovens, corações normais).65 , 66 Em pacientes com FA paroxística ou persistente sintomática é indicação Classe IIa. Situações apropriadas para esta estratégia são pacientes com pausas sintomáticas na reversão (síndrome de taquibradi)67 ou atletas competitivos, que frequentemente tem contraindicação ao uso de fármacos.

2) FA em pacientes com insuficiência cardíaca (IC):

A IC pode predispor um indivíduo à ocorrência de FA através de vários mecanismos, como o aumento da pressão de enchimento do ventrículo esquerdo ou a dilatação e a fibrose do AE, levando à remodelação estrutural e elétrica do átrio. A FA pode aumentar a mortalidade em pacientes com disfunção ventricular esquerda,68 portanto, o tratamento da FA nesse subconjunto de pacientes é de importância crucial,69 - 73 dadas as limitações da amiodarona, único medicamento antiarrítmico disponível para esse subgrupo. As mais recentes diretrizes europeias de 2020 referem indicação Classe IIa,15 com base em estudos comparativos com amiodarona (AATAC)69 e na publicação de estudos randomizados como o AMICA74 e CASTLE-AF,75 este último realizado em pacientes com IC grave (Fração de ejeção média 32%), demonstrando uma redução expressiva na mortalidade ou hospitalização por IC (38%) e na mortalidade cardiovascular (51%). Tais achados sem precedentes confirmam o prognóstico negativo da FA nessa população e abrem uma nova fronteira de indicações para ablação em centros com experiência e infraestrutura adequados. Resultados positivos recentes são animadores, com demonstração de melhora da função ventricular e reversão do remodelamento atrial.76

3) FA em idosos:

Há estudos que se concentraram em relatar os resultados da ablação da FA em indivíduos mais velhos. O limite de idade para a definição de idosos variou entre ≥70, 75 ou 80. O número de idosos nesses estudos foi, porém, pequeno, com cinco dos sete estudos inscrevendo menos de 100 pacientes, e os maiores resultados relatados em 261 idosos. Os resultados desses estudos fornecem evidências de que a ablação preenche critérios de segurança e eficácia nessa população,77 , 78 apesar de redução nas taxas de sobrevida livre de FA a cada década de idade (Classe IIa).

4) FA em assintomáticos e redução do risco de AVC:

Ablação da FA (paroxística ou persistente) em pacientes realmente assintomáticos pode ser considerada,79 a despeito das poucas evidências de significativa mudança em desfechos “duros” – em particular no risco de fenômenos tromboembólicos/AVC. Deve ser realizada por operador experiente e após uma discussão detalhada dos riscos e benefícios da realização do procedimento (Classe IIb). Há sólidas evidências de redução de hospitalizações80e uso de recursos, com relação custo-benefício favorável.10 Nesse cenário, deve-se priorizar pacientes com alta probabilidade de sucesso (jovens, FA paroxística, sem remodelamento atrial significativo).

Diversos estudos retrospectivos observacionais apontam para uma significativa redução do risco tromboembólico em pacientes com escore CHADSVASC ≤3 submetidos à ablação bem-sucedida,81 - 87 muitos deles reportando até desfechos favoráveis em pacientes que interromperam a terapia anticoagulante. Dados do estudo KP-RHYTHM88comprovando que a o risco de AVC é proporcional à carga de FA em pacientes paroxísticos, independentemente do escore CHADSVASC, e metánalise de estudos randomizados89 sugerindo redução de mortalidade e hospitalizações, são compatíveis com a hipótese de redução de risco após uma ablação bem-sucedida.

É preciso ressaltar, porém, que não há evidência direta de estudos randomizados especificamente desenhados para este objetivo; o estudo CABANA7 não demonstrou redução em desfechos combinados em uma população heterogênea (FA paroxística e persistente) submetida à ablação versus tratamento medicamentoso. O recém-publicado EAST-AFNET 490 demonstrou significativo benefício em desfechos cardiovasculares com uma estratégia inicial visando ao controle do ritmo quando comparado com o controle da frequência cardíaca. Contudo, nesse importante estudo randomizado, apenas 20% dos pacientes foram tratados com ablação.

Por isso, todas as diretrizes atuais recomendam que o tratamento ablativo não tenha como objetivo a suspensão da terapia anticoagulante,11 - 14 que deve ter sua indicação a partir do risco de base do paciente (usualmente indicada em pacientes com escore CHADSVASC ≥2). Todos os pacientes submetidos à ablação devem ficar sob uso de anticoagulantes por período mínimo de 2 meses, independentemente dos fatores de risco, e sua continuação por período indeterminado deve ser individualizada pelo escore de risco.

O estudo OCEAN,91 em andamento, compara a manutenção da anticoagulação (rivaroxabana) com o ácido acetilsalicílico em pacientes de risco moderado a severo submetidos à ablação e mantendo ritmo sinusal por pelo menos 1 ano após o procedimento. Os resultados devem ajudar a refinar as indicações de anticoagulação a longo prazo pós-ablação.

Complicações

O procedimento de ablação está associado a pequenas taxas de complicações em centros de excelência com grande volume e experiência, sendo as mais graves complicações individualmente menores que 1% nos centros com maior experiência.11 A Tabela 5 resume as principais complicações e suas incidências relatadas na literatura.

Tabela 5. Complicações relacionadas à ablação da fibrilação atrial.

Complicações Incidência Teste diagnóstico
Morte <0,1% a 0,4% -
Estenose/oclusão de artéria coronária <0,1% Cineangiocoronariografia
Fístula atrioesofágica 0,02% a 0,11% TC/RM; evitar endoscopia com insuflação de ar
Embolia aérea <1% Clínica ou angiografia
Estenose VP <1% TC/RM
Síndrome do AE duro <1,5% Eco; cateterismo cardíaco
Paralisia permanente do nervo frênico 0% a 0,4% Raio X do tórax; fluoroscopia; Sniff test
AVC/AIT 0% a 2% TC/RM; angiografia cerebral
Complicações vasculares 0,2% a 1,5% Ultrassom vascular; TC
Tamponamento cardíaco 0,2% a 5% Eco
Pericardite 0% a 5% Clínica; ECG; Eco
Gastroparesia 0% a 17% Endoscopia; deglutição de bário; estudo do esvaziamento gástrico

TC: tomografia computadorizada; RM: ressonância magnética; VP: veia pulmonar; AE: átrio esquerdo; AVC: acidente vascular cerebral; AIT: ataque isquêmico transitório; ECG: eletrocardiograma.

É importante estar atento a uma complicação tardia (nas primeiras semanas) relacionadas à lesão esofagiana devido à proximidade desse órgão com a parede posterior do AE. Durante a aplicação de energia nessa região, deve-se reduzir a potência e o tempo de aplicação, além do monitoramento da temperatura esofágica luminal ( Tabela 4 ). Uma alternativa já em uso corrente consiste em diversos modos de desvio do trajeto do esôfago, de forma a distanciá-lo do local de aplicação de RF.92 - 95 Há relatos de fístulas atrioesofágicas, com elevado índice de mortalidade.96 - 100 Felizmente, essa complicação tem incidência estimada ao redor de 0,04%, mas seu reconhecimento precoce pode ser fundamental para evitar um desfecho fatal.99 , 101 - 103

Perspectivas futuras

O uso de alta potência de RF com curta duração ( high power short duration ) tem sido advogado como um modo de produzir lesões teciduais de melhor qualidade,104 , 105 além de provocar lesões mais largas e de menor profundidade e, portanto, com menor risco de danos colaterais (especialmente ao esôfago). Essa técnica foi associada a menor tempo de aplicações de RF e de instrumentação do átrio esquerdo e baixos índices de complicações,106 , 107 impulsionando novas investigações de cateteres que possam fazer lesões mais permanentes em poucos segundos de aplicação.108

Há uma grande expectativa com o desenvolvimento de uma nova modalidade de energia para ablação, denominada “eletroporação”. Diferentemente das energias térmicas (RF, crioterapia, laser , ultrassom e micro-ondas), cuja propensão é eliminar todos os tecidos indiscriminadamente, a ablação por campo pulsado ou “eletroporação” é uma modalidade ablativa não térmica, na qual os campos elétricos ultrarrápidos (<1s) são aplicados ao tecido-alvo de forma seletiva, desestabilizando as membranas celulares e culminando em morte celular. Isso é possível, pois os tecidos têm diferentes limiares para necrose. Essa tecnologia é usada para tratar tumores sólidos irressecáveis devido à proximidade de vasos sanguíneos ou nervos, dada a resistência a campos elétricos pulsados.109 , 110 Os cardiomiócitos têm um dos limiares de lesão tecidual mais baixos, podendo, por isso, ser aplicados limitando o dano colateral, como o esôfago111e o nervo frênico.112

Experiência inicial em pacientes submetidos a isolamento ultrarrápido das VP é bastante promissora, com índices de isolamento permanente nunca antes obtidos (100%).113 Essa tecnologia tem grande potencial para substituir definitivamente a RF e outras energias térmicas para tratamento da FA por cateter.

O estudo ERADICATE-AF,114 recentemente publicado, avaliou o efeito adicional da denervação renal por cateter em 302 pacientes hipertensos submetidos à ablação de FA, randomizados para isolamento das VP simples ou combinado à ablação na artéria renal. Nesse estudo, a adição da denervação resultou em melhor sobrevida livre de FA aos 12 meses (72% vs. 56%). Esses achados certamente necessitam ser replicados em um modelo cego ( sham procedure ) de denervação renal, porém, a modulação do sistema nervoso autônomo é um mecanismo fisiopatológico importante e que deve ser melhor explorado.

Conclusão

A ablação por cateter é o método mais eficaz para controle do ritmo em pacientes com FA, associada à expressiva redução dos sintomas, da carga de FA e das internações hospitalares, com significativa melhora na qualidade de vida. É associada a baixas taxas de complicações quando realizada em centros experientes. Seu papel na redução de eventos tromboembólicos e na mortalidade ainda necessita de comprovação definitiva em futuros estudos randomizados, apesar desta forte tendência nos dados atualmente disponíveis.

Vinculação acadêmica

Não há vinculação deste estudo a programas de pós-graduação.

Fontes de financiamento .O presente estudo não teve fontes de financiamento externas.

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Arq Bras Cardiol. 2021 Feb 19;116(2):334–345. [Article in English]

Atrial Fibrillation (Part 2) - Catheter Ablation

Eduardo B Saad 1,2, Andre d’Avila 3,4

Abstract

More than 20 years since its initial use, catheter ablation has become a routinely performed procedure for the treatment of patients with atrial fibrillation (AF). Initially based on the electrical isolation of pulmonary veins in patients with paroxysmal AF, subsequent advances in the understanding of pathophysiology led to additional techniques not only to achieve better results, but also to treat patients with persistent forms of arrhythmia, as well as patients with structural heart disease and heart failure.

Keywords: Arrhythmias Cardiac, Fibrilation Atrial, Catheter Ablation/methods, Echocardiography/methods


Significant technological advances, especially in 3D electroanatomic mapping, intracardiac echocardiography use and how energy is delivered to the tissue (cryoablation and tissue contact force with radiofrequency) have allowed a significant reduction in the rate of complications and in the use of ionizing radiation.

Currently, ablation is the most efficient treatment for patients with AF, and an excellent alternative to the use of antiarrhythmic drugs, whose development has been insignificant in recent decades.

With the pioneering observations made by Haissaguerre et al.,1the pivotal role of arrhythmogenic foci located in the pulmonary veins (PV) in the pathophysiology of the initiation and maintenance of AF episodes was shown. The concept of focal AF was then established, where atrial arrhythmia that diffusely affects both atria have a well-determined origin, and is therefore susceptible to therapeutic interventions. Techniques using catheter ablation were developed and improved to eliminate AF-generating foci through circumferential ablation around the PVs,2 - 4with higher success and performance rates compared to the best pharmacological therapy.5 - 10

The aim of this article is to review the advances in catheter ablation for AF and describe to the clinical cardiologist state-of-the-art indications, techniques, results and complications.

Ablation Strategies

Over the last 20 years, several ablation strategies have been used to control AF. In common, there is a current consensus that the isolation of all PVs is fundamental in all groups of patients (paroxysmal, persistent or long-standing persistent AF).11 - 15Isolation must be electrically proven by circular mapping inside the PVs (Figures 1 and 2), as this step is paramount for the success of the procedure. Recent studies have shown that the procedure should be performed on uninterrupted oral anticoagulation, a strategy proven to reduce thrombotic and hemorrhagic complications.16 - 18

In patients with paroxysmal AF, PV isolation is usually all that is needed, targeting additional sites only in specific situations (e.g., triggering foci mapped outside the PVs). Some centers routinely perform isolation of the superior vena cava19 , 20since it can also be, albeit rarely, a triggering AF-inducing source. Most publications show favorable results, with success rates above 70%.6

PV isolation can be performed using: 1) radiofrequency (RF) energy, through point-by-point focal applications ( Figure 1 – A), ideally with catheters with contact force sensors at the tip ( Figure 1 – B), or 2) freezing (cryoablation), using a balloon catheter positioned in the antrum of the PVs, capable of performing ablation simultaneously around the entire circumference in contact with the tissue ( Figure 1 - D). A randomized study (Fire and ICE)21directly comparing the two strategies for the treatment of paroxysmal AF showed similar results. These findings were replicated in a second randomized study (CIRCA-DOSE)22that compared two cryoablation regimens (4 min vs. 2 min freezings) to the use of contact force-guided RF to isolate the PVs in patients with paroxysmal AF; in this study, there was a >98% reduction in AF burden demonstrated through continuous electrocardiographic monitoring. It is important to note that the Cryo balloon catheter is not commonly used for ablation at sites other than around the PVs; when necessary, an RF catheter should be used for that ( Figure 1 - C).

Figure 1. – Catheter ablation for the treatment of paroxysmal AF. A) Isolation of left VPs by circumferential ablation (RF point-by-point) guided by 3D electroanatomic mapping (NAVx system — Abbott), demonstrating the elimination of electrograms (*) recorded by a circular catheter inside the PVs. B) Isolation of the right PVs (CARTO system — Biosense Webster) with a contact force-sensing catheter (shown by the force vector and force quantification = 7 g); the circular mapping catheter is inside the right superior PV. C) Persistent AF ablation (NAVx system — Abbott) demonstrating the additional linear RF lesions to isolate the LA posterior wall (roof and inferior lines), leading to the elimination of electrograms (recorded by the circular mapping catheter). D) Fluoroscopic imaging during cryoablation for isolation of the left superior PV, demonstrating the balloon catheter (arrow) inflated and in contact with the vein ostium. Balloon ablation along the PV circumference is performed simultaneously, which is usually restricted to PV isolation — when additional ablation is required, an RF catheter should be used.

Figure 1

In persistent and long-standing persistent forms of AF, additional electrical conduction barriers are often created, as stand-alone PV isolation is usually insufficient and associated with high recurrence rates.23 - 25Several strategies have been studied,26 - 37the most frequently used being: ablation of triggers outside the PVs, linear lesions in the left atrium (LA) and extensive RF applications at sites depicting fractionated electrograms during AF (most commonly observed in the posterior LA wall, septum, LA roof, mitral annulus, base of the left atrial appendage (LAA) and inside the coronary sinus). During RF applications at these sites, AF conversion to regular atrial tachycardias or even to sinus rhythm may occur.

The negative results of the randomized Star AF II38study should be noted. The study compared the addition of linear lesions and ablation of fragmented potentials to PV isolation in patients with persistent AF. In this study, there was no difference in the rates of sinus rhythm maintenance at 18 months between the groups (59% for PVI only vs. 49% and 46% in the other groups, without statistical significance). Therefore, many centers still perform PV isolation only, even in patients with persistent AF.

A more aggressive strategy for eliminating AF triggers was also tested in a randomized controlled trial (BELIEF Trial),39by electrical isolation of the left atrial appendage (LAA). Isolation of this structure in addition to conventional ablation was associated with a 55% reduction in the relative risk of AF recurrence in patients with long-term persistent AF. LAA isolation is currently performed selectively as it requires extensive RF applications and its association with increased risk of embolic phenomena (due to the loss of LAA contraction leading to slow flow and thrombus formation). Patients with electrically isolated LAA should be permanently anticoagulated, regardless of the CHADSVASC score, and should undergo occlusion of this structure if anticoagulation is contraindicated.40

Therefore, more persistent forms of AF with significant atrial remodeling require modification of the atrial substrate, implying a greater number, sites and extent of RF applications. There is no consensus in the literature on the best strategy to be used ( Table 1 ). The evolution of AF to persistent forms represent progression of a pathological process (atrial myopathy)41 , 42and should motivate earlier intervention, ideally when AF is still paroxysmal, and LA remodeling is not yet present. A large retrospective study with more than 4,500 patients analyzed the impact of time between the diagnosis of AF and ablation therapy.43The results are striking, demonstrating that the earlier the ablation is performed the better the results – establishing the so called “oncological concept of AF”, that is, the best results are obtained when treatment is done in the early stages of the disease (PV isolation in paroxysmal AF). In more advanced diseases (persistent and long-standing persistent AF), treatment is usually much more extensive and associated with worse results. A message to cardiologists and clinicians caring for AF patients is that the sooner the better.

Table 1. – Atrial fibrillation Ablation Strategies.

For PV Isolation:
Class I – A PV isolation is recommended for all AF ablation procedures
Class I – B Demonstration of PV entrance block
Class IIa – B Monitor for PV reconnection for 20 minutes after initial isolation
Class IIb – B
  • Adenosine administration 20 minutes after PV isolation

  • Pacing along the circumferential ablation line

  • Demonstration of PV exit block

In addition to PV isolation:
Class I – B CTI ablation in patients with history of typical flutter or if the arrhythmia is inducible during AF ablation
Class I – C If linear lesions are performed, bidirectional block should be demonstrated
Class IIa – C
  • If reproductible non-PV triggers are identified, ablation should be considered

  • When using a contact force-sensor catheter, a minimum of 5-10 g is reasonable

Class IIb – B
  • LA posterior wall isolation can be considered for initial or redo procedures for persistent or long-standing persistent AF

  • High dose Isoproterenol for non-PV trigger detection and ablation can be considered for initial or redo procedures for paroxysmal, persistent, or long-standing persistent AF

PV: pulmonary vein; AF: atrial fibrillation; ICT: cavo-tricuspid isthmus; LA: left atrium.

Technologies to guide ablation

Regardless of the strategy used, imaging-based mapping methods are often used in addition to traditional electrophysiological mapping. Two types of technology are appropriate in this setting:

a) Electroanatomic mapping – this form of 3D mapping allows to accurately define the anatomy of the atrial cavities and the PVs, depict the functional substrate by measuring tissue voltage, mark the RF lesions spots ( figure 1 ) on the constructed map and color-code the electrical activation information obtained. It is also possible to navigate on images of the true anatomy obtained by computed tomography or magnetic resonance imaging. 3D mapping is especially useful to reduce exposure to fluoroscopy and to make easy to show electrical activation of the arrhythmia circuit or focus as well as the RF lesions performed to treat them. Two systems are currently available in Brazil: CARTO — Biosense Webster and NavX — Abbott.

b) Intracardiac echocardiogram (ICE) – through an ultrasound catheter initially positioned (but not limited to) in the right atrium, it is possible to obtain detailed real-time images of cardiac anatomy44 , 45and visualize precise and safe manipulation of catheters through the various cardiac structures ( Figure 2 ). Its use also allows the safe performance of transeptal punctures under direct visualization and the early detection of acute complications (pericardial effusion, thrombi). A recent study with more than 100,000 patients undergoing AF ablation showed the importance of this imaging method in significantly reducing the risk of a severe complication: cardiac perforation.46In this contemporary series, failure to use ICE was the greatest risk factor for cardiac perforation (RR 4.85).

Figure 2. Use of intracardiac echo (ICE) during AF ablation. A) Schematic diagram showing the ICE catheter in the right atrial cavity with the ultrasound beam directed to guide the two transeptal punctures and positioning of circular mapping and ablation catheters in LA. B) ICE image demonstrating PV antral positioning and tissue contact during RF delivery around the left superior PV (VPSE). LA: left atrium; LAA: left atrial appendage; Map: mapping catheter; RF: ablation catheter.

Figure 2

These non-fluoroscopic imaging tools have been increasingly used in the EP laboratory over the years and can even guide the entire ablation procedures, completely avoiding the use of X-rays.47Initially reported approximately 10 years ago, “Zero-Fluoro” techniques are increasingly used in the electrophysiological community because they have been shown as safe and effective as traditional methods guided by fluoroscopy.48 - 50

Recurrences

Two main factors justify AF recurrences after ablation:

1. Reconnection or recurrent conduction in the PVs – for circumferential lesions to provide permanent PV isolation, contiguous fibrous tissue formation should form usually four to eight weeks after the acute injury (energy-induced tissue edema). If the lesion is not deep enough in the atrial wall, there may be remaining viable tissue after edema resorption. It only takes a small recovered segment to restore electrical PV-LA connection.

2. Occurrence of ectopic foci outside the PVs (non-PV triggers) – these occur more commonly (but not only) in persistent forms of AF or in patients with significant atrial remodeling.

PV reconnection is easily solved with new RF applications in conduction gaps. Reintervention is usually quick, easy and safe. In paroxysmal AF, it increases the control rates of AF in approximately 95% of cases. With the use of catheters with contact-force sensors, it has become an increasingly rare phenomenon51 - 53as RF lesions tend to be deeper and permanent.54

Non-PV triggers represent a more diffuse atrial substrate; their recognition and extensive ablation are necessary to improve outcomes, without which arrhythmia control is usually not possible.33 , 54 , 55They are most commonly located at the LA posterior wall, LAA and coronary sinus32 , 54— structures that can also be isolated by RF applications. It is certainly possible to maintain sinus rhythm in the long term, even if more than one intervention if necessary.

Patient Selection and Results

The selection of patients for catheter ablation of AF is currently mainly based on the failure of medical therapy ( Table 2 ). According to the last HRS/EHRA/ECAS/APHRS/SOLAECE consensus of experts in 2017,11the primary indication for AF ablation is the presence of symptomatic paroxysmal or persistent AF, refractory or intolerant to at least one class I or III antiarrhythmic drug. There is solid evidence for improved quality-of-life parameters in these patients.5 , 56

Table 2. – Indications for atrial fibrillation ablation.

Symptomatic AF, refractory or intolerant to at least 1 antiarrhythmic drug (class I or III):
Class I – A Paroxysmal AF
Class IIa – B Persistent AF
Class IIb – C Long-standing persistent AF
Symptomatic AF, before initiation of antiarrhythmic drugs (Class I or III):
Class IIa – B Paroxysmal AF
Class IIa – C Persistent AF
Class IIb – C Long-standing persistent AF
Indications for patient populations underrepresented in clinical trials:
Class IIa – B
  • Congestive heart failure

  • Older patients (≥ 75 years)

  • Hypertrophic cardiomyopathy

  • Younger patients (≤ 45 years)

  • Brady-tachy syndrome

Class IIa – C Athletes with AF
Class IIb – C Asymptomatic AF

AF: atrial fibrillation.

AF ablation can be performed in patients with various types of heart disease (coronary artery disease, left ventricular hypertrophy, heart failure) and clinical presentations of AF (paroxysmal, persistent or long-lasting persistent), but the best results are obtained for patients with structurally normal hearts. In the largest randomized study that compared ablation with pharmacological therapy (CABANA),7survival free of recurrent AF is significantly better (HR 0.53) in ablated patients compared to those who remained on multiple antiarrhythmic drugs. Nevertheless, in this study, there was no reduction in a combined hard endpoint (death, stroke, severe bleeding or cardiac arrest) in the “intention-to-treat” analysis, although there were problems with large crossover rates for the ablation group (27%). In this study, the subgroups that benefited the most were the youngest (<65 years) and patients with congestive heart failure.

The selection of patients with persistent and long-standing persistent forms of AF follows the same reasoning, but the decision should be individualized according to parameters of remodeling such as LA size or volume57(which is an important predictor of recurrence) and AF duration. Persistent AF is a heterogeneous disease, with different degrees of atrial fibrosis and with influence of the autonomic nervous system and other pathophysiological processes still poorly understood, which explains the heterogeneous results observed with different ablation strategies. Targeting this type of AF requires an individualized definition of the substrate and mechanisms involved.58 , 59

It is important to note that even with the strategy of extensive RF applications described above, higher recurrences rates and need for reinterventions are observed. In the experience of Natale et. al., 60% of patients maintained sinus rhythm without drugs after the first procedure.54In those undergoing a second intervention, 80% maintained sinus rhythm. Table 3 summarizes some of the main published studies.

Table 3. – Trials in atrial fibrillation ablation.

Trial (year) Type Ablation Strategy N Follow-up months Sinus Rhythm Maintenance p-value
Paroxysmal AF
Thermocool AF (2010) Randomized Ablation or AAD; multicentric PVI CFAE and lines optional 167 12 66%/16% <0.001
STOP AF (2013) Randomized Cryoablation or AAD; multicentric PVI 245 12 70%/7% <0.001
SMART AF (2014) Non-randomized; contact force-sensors; multicentric; PVI CFAE and lines optional 172 12 72.5%/NA <0.0001
TOCCASTAR (2015) Randomized contact force-sensors or not; multicentric PVI CFAE, non-PV triggers and lines optional 300 12 67.8%/69.4% 0.0073*
RAAFT-2 (2014) Randomized Ablation or AAD (1stline); multicentric PVI non-PV triggers optional 127 24 45%/28% 0.02
MANTRA-PAF (2012) Randomized Ablation or AAD (1stline); multicentric PVI + roof lines mitral and ICT lines optional 294 24 AF burden: 13%/19% -
FIRE and ICE (2016) Randomized RF or Cryo; multicentric PVI 762 12 64.1% (RF)/65.4% (Cryo) -
CIRCA DOSE (2019) Randomized RF or Cryo 4 min or Cryo 2 min; multicentric PVI 346 12 53.9% (RF)/52.2% (Cryo 4 min)/51.7% (Cryo 2 min) 0.87
Persistent AF
TTOP (2014) Randomized Ablation or AAD / DCC PVI + CFAE 210 6 56%/26% < 0.001
SARA (2014) Randomized Ablation or AAD; multicentric PVI CFAE and lines optional 146 12 70%/44% 0.002
STAR AF II (2015) Randomized 3 ablation strategies; multicentric PVI; PVI + CFAE; PVI + lines 589 18 59%/49%/46% 0.15
Paroxysmal or Persistent AF
CABANA (2019) Randomized Ablation or AAD; multicentric PVI additional ablation optional 2204 48.5 69%/50% -

AF: atrial fibrillation; RF: radiofrequency; AAD: antiarrhythmic drugs; PVI: pulmonary vein isolation; CFAE: complex fractionated atrial electrograms; DCC: direct current cardioversion; * non-inferiority.

Catheter ablation is less effective in certain subgroups of patients,60where advances in pathophysiological knowledge are still needed: dilated and fibrous atria, persistent or long-standing AF, hypertrophic cardiomyopathy, amyloid infiltrate, obesity and sleep apnea.

Long-term follow-up of patients undergoing catheter ablation shows the occurrence of late recurrences,61 - 63around 7% per year in the first 5 years. It should be noted that the estimation of the actual success of ablation is hampered by inconsistencies and heterogeneities in the definitions of success and recurrences in the different published studies. As an example, most studies consider as a recurrence any atrial arrhythmia lasting more than 30 seconds, a definition with clearly little clinical significance. In this scenario, the AF burden should be more valued and clinically meaningful in future research.

As new technologies and experiences tend to promote permanent PV isolation, recurrence is currently more frequently observed due to the appearance of non-PV triggers, which should be identified and addressed32 , 33 , 54 , 64. Therefore, it is important to maintain periodic monitoring of patients and it is prudent to maintain anticoagulant therapy in patients at higher risk who do not have contraindications.

Table 4 summarizes adjuvant care to maximize the safety and efficacy of the ablation procedure.

Table 4. – Adjunctive Strategies for atrial fibrillation ablation.

Not directly related to the AF ablation procedure:
Class IIa – B
  • Weight loss

  • Evaluate BMI for ablation procedure

  • Screen for sleep apnea signs and symptoms

  • Treat sleep apnea

Class IIb – C
  • Interruption of AAD before ablation to improve long-term results is not clear

  • AAD use during blanking period (3 months) after ablation to improve results is not clear

Reducing risk during ablation procedure:
Class I – B Clear delineation of PV ostia to avoid energy delivery inside the PVs
Class I – C Reduce the energy power delivered in the LA posterior wall near the esophagus
Class IIa – C Use a temperature sensor probe in the esophageal lumen and guide energy titration

AF: atrial fibrillation; AAD: antiarrhythmic drugs; BMI: body mass index; PV: PV: pulmonary vein; LA: left atrium.

Special Situations

International guidelines published in 2016 and 2017 and updated in 2019 and 2020 by different international societies (SBC/HRS/EHRA/ECAS/APHRS/ACC/AHA/ESC/EHRA)11 - 13 , 15almost consensually recommend ablative treatment in special situations ( Table 2 ):

1) Ablation as first-choice therapy:

Increasing safety and efficacy allow ablation to be offered as first-line therapy for treatment (even before the use of antiarrhythmic drugs) in some special situations (athletes, young people, normal hearts).65 , 66It is a Class IIa indication for patients with symptomatic paroxysmal or persistent AF. Other appropriate situations for this strategy are patients with symptomatic pauses upon arrhythmia interruption (brady-tachy syndrome)67or in competitive athletes, who may have contraindications to antiarrhythmic drug use.

2) AF in patients with Heart Failure (HF):

HF may predispose to AF occurrence through various mechanisms, such as increased left ventricular filling pressures or LA dilatation and fibrosis, leading to atrial structural and electrical remodeling. AF can increase mortality in patients with left ventricular dysfunction.68Treatment of AF in this subset of patients is of critical importance69 - 73given the limitations of Amiodarone, the only antiarrhythmic drug available for this subgroup. In the most recent European guidelines published in 2020, AF ablation in patients with HF received a Class Ia15indication based on comparative studies with Amiodarone (AATAC)69and the publication of randomized studies such as AMICA74and CASTLE-AF,75the latter performed in patients with severe HF (mean EF 32%), demonstrating a significant reduction in mortality or hospitalization for HF (38%) and cardiovascular mortality (51%). These unprecedented findings confirm the negative prognosis of AF in this population and open a new frontier of indications for ablation in centers with adequate experience and infrastructure. Recent positive results are encouraging, with demonstration of improvement in ventricular function and reversal of atrial remodeling.76

3) AF in the elderly:

There are studies that have focused on reporting the results of AF ablation in older individuals. The age limit for the definition of elderly ranged from ≥70, 75 or 80 years. However, the number of elderlies in these studies was relatively small, with five of the seven studies enrolling less than 100 patients and the largest series reporting on 261 patients. Overall, the results of these studies provide evidence that ablation meets safety and efficacy criteria in this population,77 , 78despite a reduction in AF-free survival rates with every decade of age (Class IIa).

4) AF in asymptomatic patients and reduced risk of stroke:

Ablation of AF (paroxysmal or persistent) in truly asymptomatic patients can be considered79despite the lack of definitive evidence of significant changes in hard outcomes – particularly in the risk of thromboembolic phenomena/stroke. It should be performed by experienced operators and after a detailed discussion of the risks and benefits (Class IIb). There is solid evidence of reduction of hospitalizations80and resource utilization, with favorable cost-effectiveness.10In this scenario, patients with a higher probability of success should be prioritized (young people, paroxysmal AF, without significant atrial remodeling).

Several retrospective observational studies point to a significant reduction in thromboembolic risks in patients with CHADVASC score ≤3 undergoing successful AF ablation,81 - 87many of them reporting favorable outcomes even in patients who discontinued anticoagulant therapy. Data from the KP-RHYTHM88study, proving that the risk of stroke is proportional to the burden of AF in paroxysmal patients, regardless of CHADVASC score, and a metanalysis from randomized studies89suggesting reduced mortality and hospitalizations, are compatible with the hypothesis of risk reduction after a successful ablation.

It should be emphasized, however, that there is no direct evidence from randomized studies specifically designed for this purpose; the CABANA7trial did not show any reduction in a combined endpoint in a heterogeneous population (paroxysmal and persistent AF) comparing ablation versus drug treatment. The recently published EAST-AFNET 490demonstrated a significant benefit in cardiovascular outcomes with a strategy of early rhythm control compared to heart rate control, but in this important randomized study, only 20% of patients were treated with ablation.

All current guidelines recommend that ablative treatment should not aim at discontinuation of anticoagulant therapy,11 - 14which should have its indication based on the baseline risk of the patient (usually indicated in patients with CHADSVASC score ≥ 2). All patients undergoing ablation should use anticoagulants for a minimum period of 2 months regardless of risk factors, and its continuation should be individualized by the risk score.

The ongoing OCEAN91study compares the maintenance of anticoagulation therapy (Rivaroxaban) with Aspirin in patients at moderate to severe risk undergoing ablation and maintaining sinus rhythm for at least 1 year after the procedure. The results should help refine indications of long-term anticoagulation after ablation.

Complications

The ablation procedure is associated with low complication rates in centers of excellence with high volume and experience, with major complications individually lower than 1% in highly experienced centers.11 Table 5 summarizes the main complications and their incidences as reported in the literature.

Table 5. – Complications Related to AF Ablation.

Complications Incidence Diagnostic test
Death <0.1% – 0.4% -
Coronary stenosis / occlusion <0.1% Coronary angiogram
Atrio-esophageal fistula 0.02% – 0.11% CT/MRI; avoid endoscopy with air insufflation
Air embolism <1% Clinical or angiography
PV stenosis <1% CT/MRI
Stiff LA syndrome <1.5% Echo; cardiac catheterization
Permanent phrenic nerve paralysis 0% – 0.4% Chest X-Ray; fluoroscopy; Sniff test
Stroke/TIA 0% – 2% CT/MRI; cerebral angiography
Vascular complications 0.2 – 1.5% Vascular ultrasound; CT
Cardiac tamponade 0.2% – 5% Echo
Pericarditis 0% – 5% Clinical; ECG; Echo
Gastroparesis 0% – 17% Endoscopy; barium swallow; gastric emptying evaluation

CT: computed tomography; MRI: magnetic resonance; PVI: pulmonary vein; LA: left atrium; TIA: transient ischemic attack; ECG: electrocardiogram.

It is important to be aware of a late complication (in the first weeks) related to esophageal injury due to its proximity to the LA posterior wall. During energy application in this region, power and/or time should be reduced, in addition to monitoring the luminal esophageal temperature ( Table 4 ). An available alternative consists of different methods of mechanical esophageal deviation to increase its distance from the site of energy delivery.92 - 95There are reports of atrio-esophageal fistulas, with a high mortality rate.96 - 100Fortunately, this is a rare complication, with an estimated incidence of approximately 0.04%. Its early recognition is critical to avoid a fatal outcome.99 , 101 - 103

Future Perspectives

The use of high-power RF with short duration has been advocated to produce better quality tissue lesions,104 , 105besides causing wider and shallower lesions and therefore less risk of collateral damage (especially to the esophagus). This technique was associated with shorter RF application and LA instrumentation times and low complication rates,106 , 107boosting further investigations of catheters that can cause more permanent lesions within seconds of energy delivery.108

There are great expectations for the development of a new energy source for ablation: “electroporation”. Unlike thermal energies (RF, cryotherapy, laser, ultrasound and microwave), which damages all tissues indiscriminately, pulsed field ablation (PFA) or “electroporation,” which is a non-thermal ablation modality in which ultrafast electric fields (<1 s) are applied to target tissue selectively, destabilizing cell membranes and culminating in cell death. This is possible because tissues have different thresholds for necrosis. This technology is already in use to treat unresectable solid tumors in close proximity to blood vessels or nerves, given their different resistance to pulsed electric fields.109 , 110Cardiomyocytes have one of the lowest tissue injury thresholds, and PFA can therefore be applied during catheter ablation, limiting collateral damage to nearby structures such as the esophagus111and phrenic nerve.112

Initial experience in patients undergoing ultra-fast PV isolation is very promising, with permanent isolation rates never reported before (100%).113This technology has great potential to replace RF and other thermal energies for catheter treatment of AF.

The recently published ERADICATE-AF114study evaluated the additional effect of catheter renal denervation in 302 hypertensive patients undergoing AF ablation, randomized to simply PV isolation or combined with renal artery ablation. The addition of denervation resulted in better AF-free survival at 12 months (72% vs. 56%). These findings certainly need to be replicated in a blinded model of renal denervation, but modulation of the autonomic nervous system is an important pathophysiological mechanism that should be further explored.

Conclusions

Catheter ablation is the most effective method for rhythm control in patients with AF, associated with significant improvement in symptoms, AF burden, quality of life and hospital admissions. It is associated with low complication rates when performed in experienced centers. Its role in reducing thromboembolic events and mortality still needs definitive proof in future randomized studies.

Study Association

This study is not associated with any thesis or dissertation work.

Sources of Funding .There were no external funding sources for this study.


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