A functional–anatomic mapping protocol for cardioneuroablation: A mechanistic case series

Background: Radiofrequency catheter ablation of ganglionated plexi has been used for more than 2 decades as an alternative to pacemaker implantation in patients with functional bradycardia. Despite potential efficacy and a favorable safety profile, the optimal procedural strategy remains debated, particularly regarding the identification of critical targets and the need for unilateral vs biatrial ablation. Most centers perform cardioneuroablation (CNA) using combined left and right atrial access, although emerging evidence indicates that single-atrial approaches may be sufficient in selected cases. Objective: This study aimed to develop a functional-anatomic mapping approach combining extracardiac vagal stimulation and endocardial high-frequency stimulation, repeatedly applied throughout the procedure, to reveal critical vagal pathways. Methods: In this prospective mechanistic series, 5 consecutive patients with cardioinhibitory Vasovagal Syncope International Study 2B vasovagal syncope underwent CNA using the functional-anatomic protocol. Dynamic changes in responses to extracardiac vagal stimulation and high-frequency stimulation after lesion delivery were used to infer critical vagal connections to the sinoatrial and atrioventricular nodes. Results: 5 distinct functional profiles were identified, enabling individualized strategies: 3 patients underwent right atrial-only ablation, 1 had a single left atrial approach, and 1 underwent a biatrial procedure. All patients met the heart rate increment endpoint (>15%) and showed a significant standard deviation of normal-to-normal interval attenuation. No symptom recurrence was observed over a follow-up of 13.4 ± 3.2 months. Furthermore, functional mapping revealed asymmetrical vagal innervation patterns and interganglionated plexus connectivity influencing sinoatrial and atrioventricular modulation, which aided in tailoring the procedure. Conclusion: This functional-anatomic methodology can be used to define ablation extent and procedural laterality, providing a framework to standardize CNA.