Pulsed Field Ablation Reduces Arrhythmia Recurrence in Persistent AFib

First-line treatment with pulsed field ablation (PFA) reduced the risk of recurrence of atrial arrhythmia among patients with persistent atrial fibrillation (Afib), the randomized AVANT GUARD trial showed. Among untreated patients at 12 months, short- and long-term treatment success was observed in 56% of those who received PFA with the Farapulse pentaspline catheter system compared with 30% of those who received upfront antiarrhythmic drug therapy (HR for composite treatment failure 0.46, 95% CI 0.33-0.65). The results were simultaneously published in the New England Journal of Medicine.

The PFA arm also met a prespecified safety performance goal, with safety events, namely device- or procedure-related serious adverse events, occurring in 5.1% of patients (upper confidence limit of 8.6%) in the randomized PFA arm combined with a separate PFA-assigned cohort. There was no significant excess of serious adverse events associated with PFA in AVANT GUARD (25% vs 21% for drug therapy). The overall risk of serious adverse events was similar between the two groups.

Persistent Afib, characterized as a single episode lasting more than 7 days, is associated with worse clinical outcomes compared with paroxysmal Afib. Patients with persistent atrial fibrillation often have substantial electrical and structural remodeling, which leads to worse procedural outcomes with thermal-based ablation techniques than in patients with paroxysmal atrial fibrillation. The Farapulse is a single-shot system with configurable flower or basket shapes and 20 electrodes; it has been FDA approved for paroxysmal Afib since 2024 and for drug-refractory persistent Afib since last summer.

The trial had been paused after six procedure-related strokes were observed, one of which was related to inadvertent introduction of air from the deflectable sheath. After the 3-week pause, enrollment was allowed to resume with an amended study protocol, with modifications including the exclusion of patients with CHA2DS2-VASc scores ≥4 and new requirements that patients undergo screening for left atrial thrombus within 24 hours before PFA, receive uninterrupted anticoagulation for at least 4 weeks before PFA, and have a minimum activated clotting time of 350 seconds before ablation. No neurologic events were observed after these protocol modifications.

The AVANT GUARD trial enrolled patients from 2023 to 2025 from the U.S., Europe, and Asia. After an initial roll-in phase, the investigators randomized 310 adults 2:1 to PFA or antiarrhythmic drug therapy. A separate 100-patient cohort was assigned to PFA for the safety analysis. Continuous rhythm monitoring was conducted using a LUX-Dx insertable cardiac monitor.

Atrial fibrillation affects more than 50 million people worldwide, including approximately one million Canadians, and significantly increases the risk of stroke, heart failure and early death. For decades, most patients with AFib have been treated with medications first, with catheter ablation typically reserved for patients whose symptoms persist despite drug therapy. The trial shows that, even in patients with more advanced AFib, earlier intervention with ablation can provide substantial benefits and better control of the disease.