Cardioneuroablation With a Stepwise Strategy in Patients With Cardioinhibitory and Mixed Vasovagal Syncope

Cardioneuroablation (CNA) is an emerging treatment for refractory vasovagal syncope (VVS). While biatrial approaches are common, the efficacy of a stepwise strategy-beginning with right-sided ablation and progressing to the left atrium only if necessary-remains incompletely defined. We conducted an observational, retrospective registry (2024-2025) of 57 patients (mean age 34.5 ± 16.8 years) with highly refractory cardioinhibitory (Vasovagal Syncope International Study 2A/2B, 77.2%) or mixed (Vasovagal Syncope International Study 1, 22.8%) VVS. All patients had normal intrinsic conduction verified by electrophysiological study and a positive atropine challenge. A fragmented electrogram-guided stepwise CNA was performed. Left-sided ablation was performed exclusively if right-sided ablation failed to meet predefined end points (fragmented electrogram elimination, heart rate [HR] increase >25%, and postablation atropine response <10%). Acute procedural success was achieved in 96.5% of cases. Right-sided ablation alone met denervation criteria in 30 patients (52.6%), while 27 (47.4%) required a subsequent biatrial approach. The requirement for a biatrial approach was not significantly predicted by the predominant rhythm disturbance (sinus slowing vs AV block). At a mean follow-up of 12.5 ± 6.0 months, there were 0% syncope recurrences. Significant improvements were observed at 6 months in mean HR (59.7 ± 9.9 to 79.6 ± 7.8 beat/min; p < 0.001) and in all time- and frequency-domain HR variability parameters, confirming sustained parasympathetic withdrawal. A stepwise, electrogram-guided CNA is a highly safe and effective therapy for carefully selected patients with functional VVS. Initial right-sided ablation is sufficient in over half of the cases, safely optimizing procedure time and avoiding unnecessary left atrial access without compromising clinical outcomes.