Impact of Vagal Effect on Atrial and Ventricular Refractoriness and Atrial Fibrillation: A Comparative Analysis Before and After Cardioneuroablation.

Background: Extracardiac vagal stimulation (ECVS) provides a simple, reproducible method to study human vagal effects. While vagus nerve clearly modulates atrial electrophysiology, its influence on human ventricular refractoriness remains uncertain. Likewise, the impact of cardioneuroablation (CNA) on atrial and ventricular refractoriness has not been evaluated in a paired human study OBJECTIVE: To quantify the impact of ECVS on atrial and ventricular effective refractory periods (AERP/VERP) before and after CNA and to evaluate a practical AF ablation functional endpoint.

Methods: 89 consecutive patients were enrolled (76 paroxysmal AF undergoing pulmonary vein isolation plus CNA; 13 reflex syncope undergoing CNA alone). AERP and VERP were measured at four stages: baseline, during ECVS, post-CNA, and post-CNA during ECVS. AF inducibility was tested at each stage with a single extra-stimulus (Vagal AF Induction Test, VAFIT).

Results: ECVS produced marked AERP shortening (right atrium: 213.8±25 to 100.6±33ms; left atrium: 235.2±32 to 143.3±32ms; both p<0.001). After CNA, AERP returned toward baseline and was no longer modified by ECVS. In contrast, VERP in both ventricles remained unchanged across all stages (p>0.13). AF inducibility rose from 3.4% at baseline to 95.5% during ECVS, then fell to 7.9% during ECVS post-CNA (Cochran's Q p<0.00001; McNemar p<0.00001).

Conclusions: Vagal activation is a potent atrial AF trigger, whereas ventricular refractoriness remains unchanged facing ECVS and/or CNA, underscoring chamber-specific autonomic effects and supporting the electrophysiological safety of ECVS and of CNA. ECVS and VAFIT provide objective, reproducible functional endpoints to guide ablation strategy, confirm atrial vagal denervation, and potentially reduce AF recurrence.