First-in-human experience from RESET-AF (Rapid onE-Shot Electroporation Trial for Atrial Fibrillation)

Pulsed field ablation (PFA) is increasingly used to treat patients with atrial fibrillation (AF). The RESET-AF was a single-arm, first-in-human, clinical trial of AF ablation using a novel, single-shot PFA system (ElePulse^®, CRC EP, Tustin, CA, USA), trial registration ACTRN12622001523796 (Date registered 8th December 2022).

In 36 consecutively-enrolled patients (57 ± 11 years, 69% male) with symptomatic paroxysmal (n = 22) and persistent (n = 14) AF, pulmonary vein isolation (PVI) was performed using this catheter, guided by 3D mapping. All patients underwent remapping at 3 months to confirm PVI durability. Patients were followed at 6 and 12 months with clinical review, Holter monitoring and electrocardiography. The primary efficacy and safety endpoints included a freedom from recurrent AF at 12 months > 50% and serious adverse events (SAE) at 7 and 30 days < 5%, respectively. The secondary efficacy endpoints included 3-month PVI durability > 50% and 6-month freedom from AF > 60%.

All endpoints were achieved in the entire study cohort. There was 1 SAE (renal impairment which resolved with conservative management) with a total SAE rate of 2.8%. One patient was lost to follow-up at 12 months with a primary efficacy endpoint of 92% (32/35 patients). The secondary efficacy endpoints were 82% 3-month PVI and 94% (34/36 patients) 6-month freedom from AF. During the study, the PFA dose was adjusted in 3 cohorts. The "optimized subset" had 100% PVI durability and freedom from AF at 6 and 12 months without SAEs.

This study of a novel PFA catheter system for ablation of paroxysmal and persistent AF achieved all predetermined primary and secondary clinical endpoints.