Pulsed Field Ablation As Initial Therapy for Persistent Atrial Fibrillation

Key Takeaways

• At 12 months, treatment success occurred more often with first-line pulsed field ablation than with antiarrhythmic-drug therapy in previously untreated persistent atrial fibrillation.
• All patients received an insertable cardiac monitor, and treatment success combined short-term and long-term components through 12 months.
• The primary safety end point occurred in 13 of 257 patients in the combined pulsed field ablation group, and serious adverse events were reported in both groups at 12 months.

First-line pulsed field ablation was associated with higher 12-month treatment success than antiarrhythmic-drug therapy in previously untreated persistent atrial fibrillation, with Kaplan–Meier estimates of 56% versus 30% in a NEJM trial of first-line pulsed field ablation. Investigators compared these strategies in patients who had not previously received treatment for persistent atrial fibrillation. Prespecified outcomes included a primary effectiveness end point through 12 months and safety outcomes, including a primary safety end point and serious adverse events at 12 months.

This international randomized trial enrolled patients with previously untreated persistent atrial fibrillation. Patients were assigned in a 2:1 ratio to pulsed field ablation with a pentaspline catheter or to antiarrhythmic-drug therapy. An additional PFA-assigned group underwent pulsed field ablation for analysis of the primary safety end point alone, creating a combined PFA safety population. All patients received an insertable cardiac monitor for recurrence detection during follow-up.

The primary effectiveness end point combined short-term and long-term treatment success through 12 months. In the pulsed field ablation group, short-term success meant procedural success. In the antiarrhythmic-drug group, it meant no ablation during the 90-day blanking period after treatment initiation. Long-term success from 90 days through 12 months required freedom from recurrence of atrial arrhythmias, repeat ablation, or need for antiarrhythmic drugs in the PFA group, and freedom from amiodarone use at any time in the drug-therapy group.

At 12 months, treatment success was observed in 128 of 207 patients in the PFA group and 40 of 103 in the antiarrhythmic-drug group. Kaplan–Meier estimates were 56% with PFA and 30% with drug therapy, with corresponding 95% confidence intervals of 48 to 63 and 21 to 40. The hazard ratio for composite treatment failure was 0.46, with a 95% confidence interval of 0.33 to 0.65 and P<0.001. Investigators also reported lower recurrence of atrial arrhythmia with first-line PFA than with antiarrhythmic-drug therapy. The prespecified effectiveness comparison favored pulsed field ablation at 12 months.

The primary safety end point was device- and procedure-related serious adverse events. That end point occurred in 13 of 257 patients, or 5.1%, in the combined PFA group, which included randomized and PFA-assigned patients. At 12 months, serious adverse events had occurred in 45 patients in the PFA group and 20 patients in the antiarrhythmic-drug group.