Non-Invasive Median Nerve Stimulation with a Wearable Stimulator to Reduce Atrial Arrhythmia Recurrence after Atrial Fibrillation Ablation: The NEUROPULSE Pilot.

BACKGROUND: To improve atrial fibrillation (AF) ablation success, empiric lesions are often placed - with variable effectiveness - but at the expense of myocardial destruction. Autonomic modulation may provide a non-ablative adjunct that improves rhythm outcomes without excess myocardial injury. OBJECTIVE: To evaluate cutaneous median nerve stimulation (MNS) after AF ablation. METHODS: NEUROPULSE was a 3-center, randomized, double-blind, sham-controlled pilot study. Seventy-seven patients were randomized 1:1 to active MNS (3x20-min sessions/week) or sham; the modified intention-to-treat (mITT) population included 59 patients (31 MNS, 28 sham). Treatment began within 48 hours after ablation (largely pulsed field ablation) and continued for 6 months (daily for 2 weeks, then 3 times weekly). Surveillance included twice-daily 2-minute device ECGs and 10-day patches at 2 and 6 months. RESULTS: Median age was 67 years (IQR, 56-74 years), 39% female, 68% paroxysmal AF, and 27% redo ablation. Blinding was maintained. During post-blanking follow-up (months 2-6), 12 AF/AT/AFL events occurred with MNS and 243 with sham (rate ratio [RR] 17.93; 95%CI 10.04-32.0; P<0.0001). Excluding 1 high-burden sham outlier, 12 vs 28 events occurred (RR 2.17; 95%CI 1.10-4.27; P=0.025). AF/AT/AFL recurred in 2 of 31 MNS and 5 of 28 sham patients; six-month arrhythmia-free survival was 90.0% vs 80.8% (hazard ratio 2.15; 95%CI 0.42-11.1; P=0.36), respectively. PAC counts and patient-reported outcomes did not differ. No MNS- or device-related serious adverse events occurred. CONCLUSIONS: Wearable MNS after AF ablation was associated with fewer recurrent atrial arrhythmia events. This pilot study warrants confirmation in an adequately-powered trial.