Pulsed Field Ablation of Persistent Atrial Fibrillation With Continuous Electrocardiographic Monitoring Follow-Up: ADVANTAGE AF Phase 2

Abstract

BACKGROUND: There are sparse high-quality safety and effectiveness data for pulsed field ablation (PFA) of persistent atrial fibrillation (PerAF), in which lesions beyond pulmonary vein isolation (PVI) are often placed. In addition, no large trials have used insertable cardiac monitors for continuous rhythm monitoring after ablation in patients with PerAF or after PFA in any atrial fibrillation population. In Phase 2 of the ADVANTAGE AF study (A Prospective Single Arm Open Label Study of the FARAPULSE Pulsed Field Ablation System in Subjects With Persistent Atrial Fibrillation), patients with PerAF underwent PFA for PVI and posterior wall ablation (PWA) and, in a subcohort, cavotricuspid isthmus ablation for typical atrial flutter. METHODS: Patients with PerAF underwent PVI and posterior wall ablation with the pentaspline PFA catheter and cavotricuspid isthmus with a novel focal-linear PFA catheter after intravenous nitroglycerin prophylaxis. Patients were followed up for 1 year with continuous rhythm monitoring after ablation with insertable cardiac monitors to emulate traditional intermittent monitoring for the primary efficacy end point and to examine atrial arrhythmia (AA) burden and episode duration. RESULTS: This 255-patient cohort (age, 66.7±9.3 years; female, 29%; CHA 2 DS 2 -VASc score, 2.4±1.4; body mass index, 30.9±5.3 kg/m 2 ; left atrium diameter, 4.3±0.6 cm) underwent PVI plus posterior wall ablation (99.6%/100% acute success); a subpopulation (n=141; 55.3%) also received cavotricuspid isthmus PFA, with 98.6% achieving bidirectional block without complications (ST-segment changes, ventricular fibrillation). Cavotricuspid isthmus ablation took 8±13 minutes, using 18±6 pulsed field applications and 4±2 mg IV nitroglycerin. The total procedure and atrial dwell times were 105±36 and 59±24 minutes, respectively. Mimicking traditional monitoring, freedom from AA was 73.4% with adverse events in 2.4%, both meeting prespecified end-point criteria. Freedom from recurrent atrial flutter was 97.2%. Detailed analysis of the full insertable cardiac monitor data revealed freedom from AA of ≥30 seconds in 52.0%, and no episode exceeded 24 hours in 94.0% of this PerAF cohort. Both an AA burden >0.1% and longest episode duration >1 hour were predictive of increased health care use. One-year procedural effectiveness was 71.6% and 70.0% using the thresholds of ≤0.1% burden and <1 hour duration, respectively. CONCLUSIONS: In Phase 2 of ADVANTAGE AF, the first multicenter PerAF study of PFA with continuous rhythm monitoring: (1) cavotricuspid isthmus ablation with nitroglycerin prophylaxis was safe and effective, (2) PVI plus posterior wall ablation was safe and effective, and (3) an AA burden <0.1% and AA episode <1 hour duration were end points associated with the lowest health care use. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05443594.