Efficacy and safety of pulsed-field ablation in atrial fibrillation patients with high versus low comorbidity burden: a multicenter analysis

Background Early rhythm control enhances cardiovascular outcomes in patients with atrial fibrillation (AF) and significant comorbidities. However, most evidence stems from antiarrhythmic drug-based strategies, while data on catheter ablation—especially pulsed-field ablation (PFA)—in this high-risk population remain limited. Aim This study aimed to assess the efficacy and procedural safety of pulsed-field ablation (PFA) in multimorbid AF patients. Methods Consecutive AF patients, undergoing PFA-based pulmonary vein isolation at two german electrophysiology centers between March 2023 and April 2025 were analyzed. Patients were stratified by CHA2DS-VA2 score; a score ≥4 defined high comorbidity burden. The primary endpoint was the recurrence of any atrial arrhythmia after a 60-day blanking period. The secondary endpoint addressed periprocedural safety. Arrhythmia recurrence was assessed by scheduled 72-hour Holter monitoring and 12-lead ECG during clinical follow-up visits. Results A total of 1001 patients (mean age 70 ± 11.5 years; 404/1001 [40.3%] female; 540/1001 [53.9%] suffering from paroxysmal AF) were included, of whom 282 (28.2%) had high comorbidity burden. Mean follow-up duration was 332 ± 119 days. Arrhythmia recurrence was significantly higher in patients with high versus low comorbidity burden (27.3% vs. 19.6%, p=0.0079). Recurrence was significantly associated with heart failure, diabetes and vascular disease. Age, sex, hypertension, and prior stroke showed no significant correlation. Overall periprocedural complications occurred in 35/1001 [3.5%] patients, with no significant difference between the two groups (p=0.25). Conclusion PFA for AF appears less effective in patients with high comorbidity burden, although procedural safety is comparable across groups. However, whether catheter ablation, particularly using novel technologies, is still superior to conservative therapy strategies in this high risk population is currently under investigation in randomized trials.