Safety and Effectiveness of Pulsed Field Ablation to Treat Atrial Fibrillation: One-Year Outcomes From the MANIFEST-PF Registry

Abstract

BACKGROUND: Pulsed field ablation is a novel nonthermal cardiac ablation modality using ultra-rapid electrical pulses to cause cell death by a mechanism of irreversible electroporation. Unlike the traditional ablation energy sources, pulsed field ablation has demonstrated significant preferentiality to myocardial tissue ablation, and thus avoids certain thermally mediated complications. However, its safety and effectiveness remain unknown in usual clinical care. METHODS: MANIFEST-PF (Multi-National Survey on the Methods, Efficacy, and Safety on the Post-Approval Clinical Use of Pulsed Field Ablation) is a retrospective, multinational, patient-level registry wherein patients at each center were prospectively included in their respective center registries. The registry included all patients undergoing postapproval treatment with a multielectrode 5-spline pulsed field ablation catheter to treat atrial fibrillation (AF) between March 1, 2021, and May 30, 2022. The primary effectiveness outcome was freedom from clinical documented atrial arrhythmia (AF/atrial flutter/atrial tachycardia) of ≥30 seconds on the basis of electrocardiographic data after a 3-month blanking period (on or off antiarrhythmic drugs). Safety outcomes included the composite of acute (<7 days postprocedure) and latent (>7 days) major adverse events. RESULTS: At 24 European centers (77 operators) pulsed field ablation was performed in 1568 patients with AF: age 64.5±11.5 years, female 35%, paroxysmal/persistent AF 65%/32%, CHA 2 DS 2 -VASc 2.2±1.6, median left ventricular ejection fraction 60%, and left atrial diameter 42 mm. Pulmonary vein isolation was achieved in 99.2% of patients. After a median (interquartile range) follow-up of 367 (289–421) days, the 1-year Kaplan-Meier estimate for freedom from atrial arrhythmia was 78.1% (95% CI, 76.0%–80.0%); clinical effectiveness was more common in patients with paroxysmal AF versus persistent AF (81.6% versus 71.5%; P =0.001). Acute major adverse events occurred in 1.9% of patients. CONCLUSIONS: In this large observational registry of the postapproval clinical use of pulsed field technology to treat AF, catheter ablation using pulsed field energy was clinically effective in 78% of patients with AF.

Coronary Artery Spasm During Pulsed Field vs Radiofrequency Catheter Ablation of the Mitral Isthmus

“…The pentaspline PFA catheter studied herein was designed for pulmonary vein isolation, but after regulatory approval, it has been used for mitral isthmus ablation . Most cases of PFA-related spasm, even severe spasm, are subclinical or, when clinically evident, cause only transient ST-segment changes .…”

“…Indeed, right coronary spasm occurred in 100% of patients undergoing PFA at the CTI using a multielectrode pentaspline catheter, albeit the spasm was subclinical—no ST-segment elevation, arrhythmias, or ventricular wall motion abnormalities—and attenuated by prophylactic administration of nitroglycerin . Furthermore, 2 patients undergoing PFA of the CTI developed symptomatic ST-segment elevation responsive to nitroglycerin, in one case degenerating to ventricular fibrillation requiring defibrillation …”

Clinical Outcomes by Sex After Pulsed Field Ablation of Atrial Fibrillation

“…Importantly, there were no atrioesophageal fistulas or symptomatic PV stenosis in either sex. This is consistent with prior preclinical, first in-man clinical studies and real-world experience from the MANIFEST-PF registry, demonstrating the preferentiality of myocardial tissue susceptibility to PFA …”

“…A waiver of consent was granted by the ethical committee due to the use of deidentified personal information. As previously described, MANIFEST-PF is a large multinational registry from 24 European centers, including patients (aged 18 years and older) who underwent first-ever PFA for paroxysmal AF, persistent AF, or long-standing persistent AF after regulatory approval in March 1, 2021, enrolling consecutive patients in approximately May 2022 . Patients were categorized by sex (male vs female) and evaluated for clinical outcomes of PFA within sex subgroups, including freedom from AF and adverse events.…”

“…Details of the treatment strategies and follow-up in the MANIFEST-PF registry have been previously described . During PFA, a series of high-voltage, ultrashort electric pulses are delivered to the targeted area.…”