Paroxysmal Atrial Fibrillation Ablation Using a Novel Variable-Loop Biphasic Pulsed Field Ablation Catheter Integrated With a 3-Dimensional Mapping System: 1-Year Outcomes of the Multicenter inspIRE Study

Abstract

Background - The inspIRE study 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 (AF). Methods - Subjects underwent pulmonary vein isolation (PVI) 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 (SCLs), and PV stenosis. Wave II (pivotal phase) tested i) primary safety - incidence of early onset primary adverse events (PAEs), and primary effectiveness - confirmed PVI with freedom from documented atrial arrhythmia at 12-months (12M). The study design specified an interim analysis to determine early success once 30 subjects reached 12M follow-up (FU) and all subjects reached 3M FU. 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 MRI, SCLs were detected in 4 of the first 6 subjects, after which workflow enhancements, including a 10s pause between PFA applications was implemented; subsequently, only 4 of 33 subjects had SCLs. In the Wave II phase, no PAE was reported. Upon declaring early success, 83 subjects reached 12M FU. With 100% entrance block, PVI without acute reconnection was achieved in 97.1% of targeted veins. For Wave II, the primary effectiveness endpoint per Kaplan Meier at the time of interim analysis was 70.9%; 12M freedom from symptomatic AF/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 min and 26.7 ± 14.0 min, respectively. Conclusions - The inspIRE trial confirmed the safety and effectiveness of the novel mapping-integrated PFA system.

Clinical Outcomes by Sex After Pulsed Field Ablation of Atrial Fibrillation

“…In the MANIFEST-PF registry, the rate of major procedure-associated adverse events was low and consistent with other contemporary AF ablation studies using PFA and did not differ significantly between the sex groups (female: 2.5% vs male: 1.5%). Major adverse events mostly consisted of cardiac tamponade (female: 1.4% vs male: 1.0%; P = .46) and stroke (0.4% vs 0.4%, P >.99).…”

“…The primary effectiveness outcome of freedom from atrial arrhythmia recurrence (>30 seconds after blanking) was 79.0% in male patients and 76.3% in female patients at 12 months of follow-up, with greater overall effectiveness in the paroxysmal AF cohort (male: 82.5% vs female: 80.2%; P = .30) than in the persistent AF/long-standing persistent AF cohort (male: 73.3% vs female: 67.3%; P = .40). These effectiveness rates compare favorably with early clinical experience with PFA . However, none of the previous studies examining PFA for AF reported clinical outcomes according to sex.…”

“…Importantly in clinical trials, PFA has demonstrated a unique safety profile, with no reported instances of pulmonary vein stenosis or evidence of esophageal injury . Beyond the favorable safety profile, the first in-human PFA trials demonstrated an effectiveness ranging from 55% to 92% at 1 year depending on AF type, PFA technology used, and intensity of AF monitoring …”

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

“…14,15,23 The other clinical effectiveness data published with PFA were from the recently published inspIRE study (A Study for Treatment of Paroxysmal Atrial Fibrillation [PAF] by Pulsed Field Ablation [PFA] System with Irreversible Electroporation) using a different circular PFA catheter system: 186 patients with paroxysmal AF underwent PFA at 13 centers, and the 1-year Kaplan-Meier estimate of freedom from AF/AFL/AT was 70.9%. 24 Also reported recently, the 1-year clinical effectiveness in the PULSED AF study (Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF) using yet another circular PFA catheter system was 66.2% and 55.1% for paroxysmal and persistent AF, respectively. 23 In comparing these various studies, one should be cognizant that the observed higher freedom from atrial tachyarrhythmia recurrence in MANIFEST-PF may reflect differences in monitoring intensity.…”

“…14,15,23 The AF underwent PFA at 13 centers, and the 1-year Kaplan-Meier estimate of freedom from AF/AFL/AT was 70.9%. 24 Also reported recently, the 1-year clinical effectiveness in the PULSED AF study (Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF) using yet another circular PFA catheter system was 66.2% and 55.1% for paroxysmal and persistent AF, respectively. 23 In comparing these various studies, one should be cognizant that the observed higher freedom from atrial tachyarrhythmia recurrence in MANIFEST-PF may reflect differences in monitoring intensity.…”