Optimal ablation strategies for persistent atrial fibrillation remain under investigation, particularly with emerging pulsed field ablation technologies. A prospective single-center, non-randomized comparative cohort study published in Heart Rhythm evaluated an electrogram (EGM)-guided pulsed field ablation (PFA) strategy for persistent atrial fibrillation (PerAF). The study enrolled 170 patients with persistent atrial fibrillation treated using a 3D electroanatomical mapping system and a pulsed field ablation catheter.

Eighty-five patients underwent EGM-guided PFA comprising pulmonary vein isolation (PVI), posterior wall isolation (PWI), and targeted EGM ablation (EGM group), while 85 patients underwent anatomical PVI plus PWI using the same PFA system (PWI group). The procedural endpoint was atrial fibrillation (AF) termination or complete ablation of target sites.

Intra-procedural AF termination occurred in 84.7% of the EGM group compared with 11.8% in the PWI group (p < 0.001). At 12 months, freedom from AF/atrial tachycardia (AT) recurrence after a single procedure without anti-arrhythmic drugs was observed in 82.4% of the EGM group versus 65.9% of the PWI group (HR 0.47; 95% CI 0.25-0.87; log-rank p = 0.017). AF termination during the procedure was associated with higher AF/AT-free survival (84.1% vs 64.8%; HR 0.40; 95% CI 0.21-0.77; log-rank p = 0.007). One PFA-related hemolysis event occurred in the EGM group (1.2%), and no other PFA-related adverse events were observed.

EGM-guided PFA was associated with higher AF termination rates and greater arrhythmia-free survival compared with the anatomical PVI+PWI strategy.