Pulsed Field Ablation for the Treatment of Atrial Fibrillation: PULSED AF Pivotal Trial

Abstract

Background: Pulsed field ablation uses electrical pulses to cause nonthermal irreversible electroporation and induce cardiac cell death. Pulsed field ablation may have effectiveness comparable to traditional catheter ablation while preventing thermally mediated complications.

Methods: The PULSED AF pivotal study (Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF) was a prospective, global, multicenter, nonrandomized, paired single-arm study in which patients with paroxysmal (n=150) or persistent (n=150) symptomatic atrial fibrillation (AF) refractory to class I or III antiarrhythmic drugs were treated with pulsed field ablation. All patients were monitored for 1 year using weekly and symptomatic transtelephonic monitoring; 3-, 6-, and 12-month ECGs; and 6- and 12-month 24-hour Holter monitoring. The primary effectiveness end point was freedom from a composite of acute procedural failure, arrhythmia recurrence, or antiarrhythmic escalation through 12 months, excluding a 3-month blanking period to allow recovery from the procedure. The primary safety end point was freedom from a composite of serious procedure- and device-related adverse events. Kaplan-Meier methods were used to evaluate the primary end points.

Results: Pulsed field ablation was shown to be effective at 1 year in 66.2% (95% CI, 57.9 to 73.2) of patients with paroxysmal AF and 55.1% (95% CI, 46.7 to 62.7) of patients with persistent AF. The primary safety end point occurred in 1 patient (0.7%; 95% CI, 0.1 to 4.6) in both the paroxysmal and persistent AF cohorts.

Conclusions: PULSED AF demonstrated a low rate of primary safety adverse events (0.7%) and provided effectiveness consistent with established ablation technologies using a novel irreversible electroporation energy to treat patients with AF.

Registration: URL: https://www.

Clinicaltrials: gov; Unique identifier: NCT04198701.

Keywords: atrial fibrillation; catheter ablation; clinical trial; electroporation; pulsed field ablation.

Conflict of interest statement

Disclosures Drs Verma, Boersma, Calkins, Haines, Hindricks, Kuck, Marchlinski, Natale, Packer, De Lurgio, and Sanders receive consultation funds from Medtronic, Inc. Dr Onal and J. Cerkvenik are employees of Medtronic, Inc. Dr Verma receives grants or consultation funds from Biosense Webster, Bayer, Medlumics, Adagio Medical, and Boston Scientific. Dr De Lurgio receives consultation or honoraria funds from Atricure and Boston Scientific. Dr Marchlinski receives grants, consultation, or honoraria funds from Biosense Webster, Abbott Medical, and Biotronik. Dr Sood receives consultation or honoraria funds from Johnson & Johnson, Boston Scientific, Atricure, Bristol Myers, and Pfizer. Dr Boersma receives consultation funds from Boston Scientific, Abbott Medical, Adagio Medical, Acutus Medical, and Philips Medical. Dr Kuck receives consultation funds from Cardiovalve. Dr Natale receives consultation funds from Abbott Medical, Baylis, Biosense Webster, Biotronik, and Boston Scientific. Dr Sanders receives grants or honoraria funds from Boston Scientific, Abbott Medical, Becton Dickenson, Pacemate, and CathRx. Dr Tada receives funds from Abbott Medical Japan LLC, Nippon Boehringer Ingelheim Co Ltd, Daiichi Sankyo Company Ltd, Alvaus Inc, Biotronik Japan Inc, Bristol Myers Squibb, and Novartis Pharma KK. Dr Calkins receives consultation or honoraria funds from Boston Scientific, Abbott Medical, Atricure, and Biosense Webster.

Figures

Figure 1.

Catheter ablation method with pulsed field ablation system. Alternating positive and negative electrodes sustains a bipolar electrical field around the catheter that extends into the tissue. The electrical field increases cell membrane permeabilization, which then leads to cell function disruption and eventually to cell death (ie, apoptosis and necrosis).

Figure 2.

Postablation voltage map of left atrium. The map demonstrates acute pulmonary vein isolation. Gray areas represent ablated or electrically isolated tissue around the 4 pulmonary veins.

Figure 3.

Treatment success at 12 months for paroxysmal atrial fibrillation. A, Primary end point of the study. B, Any atrial tachyarrhythmia found on a Holter, ECG, or transtelephonic monitor after the blanking period is considered an event. C, Any atrial tachyarrhythmia found on a transtelephonic monitor and accompanied by patient-reported symptoms is an event. The bars on the survival curves indicate 95% CIs. AF indicates atrial fibrillation; AFL, atrial flutter; and AT, atrial tachycardia.

Figure 4.

Treatment success at 12 months for persistent atrial fibrillation. A, Primary end point of the study. B, Any atrial tachyarrhythmia found on a Holter, ECG, or transtelephonic monitor after the blanking period is considered an event. C, Any atrial tachyarrhythmia found on a transtelephonic monitor and accompanied by patient-reported symptoms is an event. The bars on the survival curves indicate 95% CIs. AF indicates atrial fibrillation; AFL, atrial flutter; and AT, atrial tachycardia.