Long-term outcomes of patients treated with pulsed field ablation under the first-in-human clinical trials with prospective invasive remap

Abstract Background Pulsed Field Ablation (PFA) is rapidly establishing itself as a leading modality in electrophysiology for the treatment of atrial fibrillation (AF), driven by its selective and predominantly non-thermal approach to tissue ablation[1]. Despite its promising short-term outcomes, comprehensive data on long-term efficacy and safety are still limited, with invasive remapping to assess lesion durability still posessing ethical challenges in certain countries. Objective This study aimed to assess the long-term clinical safety and efficacy outcomes of PFA for AF, specifically in patients who underwent protocol-driven invasive remapping as part of clinical trial protocols. Methods Patients with paroxysmal and persistent AF treated using PFA between October 2019 and January 2021 at our center were included in this retrospective analysis. All patients completed a 1-year follow-up with documented durable sinus rhythm. A total of 5 patients underwent pulmonary vein isolation (PVI) alone, while 12 patients had PVI combined with posterior wall ablation (PWA), utilizing a multielectrode pentaspline PFA catheter. Additionally, 33 patients underwent PVI using focal PFA and 5 of them also had CTI ablation using the same system. Patients were enrolled in multicenter clinical trials (PEFCATII - NCT03714178, PersAFOne - NCT04170621, ECLIPSE AF - CSP00007) at our center, with protocol-mandated remapping at 2-3 months post-procedure and standardized rhythm monitoring up to 1 year. After exiting the studies, patients continued follow-up under institutional standard of care. At a recent timepoint, follow-up was completed through an outpatient clinic visits. Results The cohort consisted of 50 patients with long-term safety and efficacy data, with an average follow-up period of 1409 ± 397 days. No adverse events related to ablation or invasive remapping occurred during the follow-up. AF recurrence was observed in 10 patients, with an average recurrence time of 825 days. Five of these patients required repeat catheter ablation for AF recurrence beyond one year. Of the 10 patients with recurrence, 8 were treated as persistent AF patients; among them, 3 initially received a lesion set of PVI plus PWA, while the remaining were treated with PVI alone. Conclusion This long-term evaluation of PFA demonstrates a robust safety profile with no late adverse events. Late arrhythmia recurrence rate appears promising, when compared with historical long-term effectiveness reports for radiofrequency ablation. The requirement for invasive remapping as part of clinical trial protocols may contribute to improved long-term outcomes by identifying and mitigating early gaps in lesion durability, potentially reducing the overall arrhythmia burden and thereby need for repeat procedures. Further long-term data are needed to fully assess the durability and safety of this emerging technology in real-world practice.Table 1