LS-PersAFone: Pulsed Field Ablation for Long-Standing Persistent Atrial Fibrillation

Among patients with paroxysmal AF, numerous randomized studies have demonstrated the efficacy of catheter ablation as compared with anti-arrhythmic therapy to prevent arrhythmia recurrence. However, among patients with long-standing persistent AF the efficacy of catheter ablation remains particularly poor, with long-term freedom from Atrial Tachycardia AT/AF off anti-arrhythmic medications generally as low as 30% after one procedure. Multiple catheter ablation procedures are usually required in long-standing persistent AF to achieve arrhythmia suppression.

Although pulmonary vein isolation (PVI) has been the main focus of catheter ablation for atrial fibrillation, as a lesion set it is insufficient for long-standing persistent AF. Electrical isolation of the posterior wall has been proposed as an adjunctive lesion set to PVI for patients with persistent and long-standing persistent AF. The left atrial posterior wall has a common embryological origin with the pulmonary veins, and differences in fiber orientation at the intersection of the pulmonary veins and the LA posterior wall may contribute to localized re-entrant circuits and subsequent AF. In addition, the posterior wall is a site of parasympathetic innervation that could act as a non-pulmonary vein trigger for AF. Typically, posterior wall isolation (PWI) during catheter ablation involves the creation of lines between the superior edge of the left- and right-sided PVI lesion sets, as well as between the inferior edges of the left- and right-sided lesion sets. Another approach involves the delivery of lesions throughout the posterior wall to target any electrical activity.

Observational studies of PWI have suggested that it improves outcomes over PVI in persistent AF. However, randomized trials of catheter ablation for PWI have not shown clinical benefit over PVI. An important possible reason for the negative results of the randomized trials is the difficulty achieving durable PWI. In fact, a recent clinical trial of a hybrid epicardial/endocardial ablation to achieve PVI and PWI was compared with a standard endocardial catheter ablation set of PVI and a roof line. The CONVERGE clinical trial of 153 patients with persistent and long-standing persistent AF showed significantly higher rate of AF burden reduction in the treatment group (74% versus 55%) by 18 months. The durability of PWI through epicardial ablation may be a major reason for the increased efficacy in the hybrid ablation group.

Left atrial posterior wall ablation is also supported by 2 important mechanistic studies-1 surgical (HISTORIC-AF) and 1 catheter based (PersAFone). Like in CONVERGE, HISTORIC-AF evaluated a 2-procedure strategy of a minimally invasive, thoracoscopic epicardial RF tool to create a posterior box lesion isolating all PVs and the posterior wall en bloc; followed 1 month later by catheter-based endocardial touch-up ablation of residual conduction gaps. This multicenter, prospective, nonrandomized study of 100 patients (32% with PerAF, 68% with longstanding PerAF) used implantable loop recorders (ILRs) for continuous ECG monitoring for AF recurrence, and nonetheless demonstrated an excellent 1-year maintenance of sinus rhythm rate of 88%. In PersAFone, patients with PerAF underwent PVI + PWI using the Farawave pulsed field ablation (PFA) catheter. While this trial only included 25 patients, the trial was notable for a design which included remapping at 3 months (demonstrating durable PWI in all patients) with any necessary touch-up ablation performed. Following this, the one-year freedom from AF recurrence was 92±5.4%.

PFA for AF offers very promising efficacy for PVI, with ~96% durability of isolated veins at 90-day remapping. Furthermore, studies of PFA for PVI have also shown an extremely low risk of esophageal injury.

Together, these data support a PFA-based PVI+PWI strategy as a simple, safe, fast approach to treat this troublesome population of long-standing PerAF patients. Accordingly, the research team proposes a prospective study of PVI and PWI for patients with longstanding PerAF, using PFA in order to minimize the risk of esophageal injury and maximize the likelihood of durable catheter-based ablation lesions. The research team seeks to obtain precise estimates of arrhythmia recurrence post-ablation through ILRs in follow-up.