BACKGROUND: The inspIRE study (Study for Treatment of Paroxysmal Atrial Fibrillation [PAF] by Pulsed Field Ablation [PFA] System With Irreversible Electroporation [IRE]) evaluated safety and effectiveness of a fully integrated biphasic pulsed field ablation (PFA) system with a variable-loop circular catheter for the treatment of drug-refractory paroxysmal atrial fibrillation. METHODS: Subjects underwent pulmonary vein (PV) isolation with the PFA system, using at least 12 applications per vein; adenosine/isoproterenol was administered to confirm entrance block. Wave I assessed initial safety, including for esophageal lesions, silent cerebral lesions, and PV stenosis. Wave II (pivotal phase) tested (1) primary safety, incidence of early-onset primary adverse events, and (2) primary effectiveness, confirmed PV isolation with freedom from documented atrial arrhythmia at 12 months. The study design specified an interim analysis to determine early success once 30 subjects reached the 12-month follow-up and all subjects reached 3-month follow-up. RESULTS: Across 13 centers in Europe/Canada, 226 subjects were enrolled, met criteria for safety and effectiveness evaluations, and received PFA (Wave I, 40; Wave II, 186). Wave I demonstrated no esophageal thermal lesions or PV stenosis. Among 39 subjects with cerebral magnetic resonance imaging, silent cerebral lesions were detected in 4 of the first 6 subjects, after which workflow enhancements, including a 10-second pause between PFA applications, were implemented; subsequently, only 4 of 33 subjects had silent cerebral lesions. In the Wave II phase, no primary adverse events were reported. Upon declaring early success, 83 subjects reached 12-month follow-up. With 100% entrance block, PV isolation without acute reconnection was achieved in 97.1% of targeted veins. For Wave II, the primary effectiveness end point per Kaplan-Meier at the time of interim analysis was 70.9%; 12-month freedom from symptomatic atrial fibrillation/atrial flutter/atrial tachycardia recurrence and repeat ablation was 78.9% and 92.3%, respectively. Total procedure and transpired PFA times were 70.1±27.7 and 26.7±14.0 minutes, respectively. CONCLUSIONS: The inspIRE trial confirmed the safety and effectiveness of the novel mapping-integrated PFA system. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; unique identifier: NCT04524364.

Cardiology Department Jessa Hospitals Hasselt Belgium

Cardiovascular Diseases University Hospital Center Split Croatia

Centre Hospitalier Universitaire de Bordeaux

Department für Kardiologie und Elektrophysiologie Akademisches Lehrkrankenhaus Ordensklinikum Linz GmbH Elisabethinen Austria

Department of Cardiology AZ Sint Jan Brugge Belgium

Department of Cardiology Na Homolce Hospital Prague Czech Republic

Department of Cardiology Ziekenhuis Oost Limburg Genk Belgium

Department of Cardiovascular Diseases Centre for Cardiology and Angiology Vilnius University Lithuania

Division of Cardiology University Heart Center Medical University Graz Austria

McGill University Health Centre McGill University Montréal Canada

Onze Lieve Vrouwziekenhuis Hospital Dienst Cardiologie Aalst Belgium

Ospedale Generale Regionale F Miulli UOC Cardiologia Acquaviva delle Fonti Bari Italy

Schulich School of Medicine and Dentistry University of Western Ontario London Canada

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Predictors of Success for Pulmonary Vein Isolation With Pulsed-field Ablation Using a Variable-loop Catheter With 3D Mapping Integration: Complete 12-month Outcomes From inspIRE

First-in-human clinical series of a novel conformable large-lattice pulsed field ablation catheter for pulmonary vein isolation

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ClinicalTrials.gov
NCT04524364