Are Genetics Useful to Guide Ablation Strategies in Patients With Persistent Atrial Fibrillation?

In the CAPLA trial, arrhythmia-free survival did not differ between patients with persistent atrial fibrillation (AF) who underwent pulmonary vein isolation (PVI) with posterior wall isolation (PWI) vs. PVI alone. High AF polygenic risk scores (PRS) have been associated with increased left atrial substrate and arrhythmia recurrence post-ablation. Whether AF patients with high AF-PRS benefit from a more extensive ablation strategy (PVI with PWI) is unknown.

To investigate the impact of adjunctive PWI on ablation outcomes in patients with persistent AF stratified by AF-PRS.

Genome-wide genotyping was performed in a CAPLA trial subgroup and a previously validated AF-PRS was derived. The primary endpoint was freedom from documented atrial arrhythmia with or without the use of antiarrhythmic drugs at 3 years after a single ablation procedure in patients with high AF-PRS who underwent PVI with PWI vs. PVI alone.

One hundred and seventy-four patients (75.29% male, median age 66.70 years) were evaluated. Mean AF-PRS was significantly higher than in a control cohort of healthy individuals (30.23 vs. 30.15; p < 0.001). Amongst patients with high AF-PRS (defined by AF-PRS corresponding to the top quartile of control cohort scores), there were no significant differences between patients who underwent PVI with PWI (n = 36) vs. PVI only (n = 49) with respect to atrial arrhythmia-free survival (p = 0.883), arrhythmia burden (p = 0.772) or quality-of-life scores (p = 0.794) over median follow-up of 3.76 years.

In patients with persistent AF undergoing ablation, the addition of PWI to PVI in those with high AF-PRS did not significantly improve long-term ablation outcomes.