First-Line PFA Reduces Recurrence in Persistent AF

Pulsed field ablation (PFA) as initial therapy was associated with a lower risk of recurrent atrial arrhythmia than antiarrhythmic-drug (AAD) therapy in patients with persistent atrial fibrillation (AFib), according to results from the AVANT-GUARD trial published in The New England Journal of Medicine.

The international, randomized trial evaluated whether PFA could be used as an initial treatment strategy in patients with previously untreated persistent AFib. The authors noted that guidelines recommend a trial of AAD therapy before catheter ablation for persistent AFib, but whether PFA may be a preferred initial treatment had remained unclear.

Investigators randomly assigned 310 patients in a 2:1 ratio to receive PFA performed with a pentaspline catheter or AAD therapy. An additional group of 100 patients underwent PFA for assessment of the primary safety endpoint only. All patients received an insertable cardiac monitor. The primary effectiveness endpoint included short-term and long-term treatment success through 12 months.

At 12 months, treatment success occurred in 128 of 207 patients in the PFA group, for a Kaplan-Meier estimate of 56% (95% CI, 48-63), and in 40 of 103 patients in the AAD group, for a Kaplan-Meier estimate of 30% (95% CI, 21-40). The hazard ratio for composite treatment failure was 0.46 (95% CI, 0.33-0.65; P<0.001). According to the American College of Cardiology summary, symptomatic atrial tachyarrhythmia recurrence lasting at least 30 seconds occurred in 2% vs 3% of patients, while asymptomatic atrial tachyarrhythmia lasting at least 1 hour occurred in 30% vs 46% of patients in the PFA and AAD groups, respectively.

A primary safety endpoint event occurred in 13 of 257 patients (5.1%) in the combined PFA group. Serious adverse events at 12 months occurred in 45 patients in the PFA group and 20 patients in the AAD group. The American College of Cardiology summary noted that the trial was temporarily paused after 6 neurologic events were observed, with enrollment resuming after independent neurologic review and protocol modifications. The investigators emphasized balancing the risks and benefits of earlier intervention through shared decision-making.

Sources: Wazni OM, Chun KRJ, Nair DG, et al. Pulsed field ablation as initial therapy for persistent atrial fibrillation. N Engl J Med. 2026;394:2407-2418. doi:10.1056/NEJMoa2600929

American College of Cardiology. AVANT-GUARD: pulsed field ablation as first-line therapy for patients with persistent AFib. Published May 5, 2026. Accessed June 29, 2026.