phrenic-safe pulsed field ablation: acute and long-term outcomes from a post hoc analysis of the Volt CE Mark and IDE Studies

Abstract Background Pulsed field ablation (PFA) has emerged as a tissue-selective energy source for atrial fibrillation (AF) ablation due to its preferential effect on myocardial tissue. This selectivity is hypothesized to reduce the risk of phrenic nerve injury (PNI), a known complication of pulmonary vein isolation. However, clinical reports indicate that PNI can still occur [1]. A novel CE-marked balloon-in-basket PFA system utilizing a lower voltage (LV) setting was developed for use in regions where phrenic nerve capture is unavoidable during ablation [2]. Purpose This post hoc analysis aimed to evaluate the acute and long-term effectiveness and safety of any low voltage (LV) setting use compared to nominal voltage (NV) only use in subjects undergoing PFA for paroxysmal (PAF) or persistent atrial fibrillation (PersAF). Methods Subjects were enrolled in the Volt CE Mark and VOLT-AF IDE studies, comprising 150 and 394 subjects, respectively. This analysis included subjects with PAF or PersAF who were categorized into four groups: PAF-LV, PAF-NV, PersAF-LV, and PersAF-NV. Baseline characteristics, acute procedural effectiveness (APE), long-term effectiveness (LTE) at 12 months, and primary safety outcomes were compared between LV and NV groups. Results A total of 166 subjects (108 PAF, 58 PersAF) received some ablation with LV, targeting the right inferior pulmonary vein (RIPV) or right superior pulmonary vein (RSPV). The LV cohort was 33.7% female and 66.3% male, with a mean age of 62.2 ± 11.1 years, and mean LAD of 39.2 ± 7.3 mm. Subjects were geographically distributed across the USA (57.2%), Australia (14.5%), and Europe (28.3%). Mean LV applications per subject were 3.3 ± 1.7 PAF and 3.1 ± 2.1 PersAF (RSPV) and 1.3 ± 1.8 PAF and 1.2 ± 1.7 PersAF (RIPV). APE was achieved in 97.2% of PAF-LV and 99.5% of PAF-NV subjects (p = 0.1312), and in 98.3% of PersAF-LV and 98.7% of PersAF-NV subjects (p = 1.000). At 12-month follow-up, LTE was 81.3% in PAF-LV and 79.9% in PAF-NV (p = 0.7854), and 72.4% in PersAF-LV versus 58.9% in PersAF-NV (p = 0.0642). A primary safety event through 7 days post-procedure occurred in 0.9% of PAF-LV and 1.5% of PAF-NV subjects (p = 1.0000), and in 1.4% of PersAF-LV and 4.4% of PersAF-NV subjects (p = 0.6852). There were no phrenic nerve related primary safety events reported in any group. In a pooled analysis of treated pulmonary veins (PVs) assessed during repeat procedures, reconnection was observed in 3/5 right-sided PVs treated with LV and 10/33 right-sided PVs treated with NV. Conclusion Use of LV in areas of unavoidable phrenic nerve capture during PFA demonstrated comparable APE and LTE to use of NV in both PAF and PersAF. Safety outcomes were consistent across all groups. These findings support the use of phrenic-safe LV to mitigate PNI risk without compromising procedural effectiveness.PAF No Significant Difference p=0.7854PersAF No Significant Difference p=0.064