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Multicenter Study
. 2025 Aug;11(8):1683-1695.
doi: 10.1016/j.jacep.2025.04.012. Epub 2025 Apr 27.

Cardioneural Ablation for Functional Bradycardia and Vasovagal Syncope: Outcomes From the U.S. Multicenter CNA Registry

Roderick Tung  1 , Margarida Pujol-Lopez  2 , Andrew H Locke  3 , Daniel M Alyesh  4 , Sri Sundaram  4 , Anand D Shah  5 , Vineet Kumar  6 , Guru Kowlgi  7 , Kapil Kumar  3 , Alexei Shvilkin  3 , Tolga Aksu  8 , Smit Vasaiwala  9 , J Peter Weiss  2 , Michael Zawaneh  2 , Jeffrey R Winterfield  10 , Leah A John  10 , Pasquale Santangeli  11 , Christopher Woods  12 , Wendy S Tzou  13 , Sunil Kapur  14 , William Sauer  14 , Amit J Thosani  15 , Thomas A Dewland  16 , Edward P Gerstenfeld  16 , Gaurav A Upadhyay  17 , Andre d'Avila  3
Affiliations
Multicenter Study

Cardioneural Ablation for Functional Bradycardia and Vasovagal Syncope: Outcomes From the U.S. Multicenter CNA Registry

Roderick Tung et al. JACC Clin Electrophysiol. 2025 Aug.

Abstract

Background: Cardioneural ablation (CNA) shows promise as a viable alternative to permanent cardiac pacing and pharmacotherapy for patients with symptomatic functional bradycardia and debilitating vasovagal syncope (VVS). The evidence supporting a potential therapeutic role for CNA is limited by relatively small sample sizes from predominantly single-center reports.

Objectives: This study sought to report the feasibility, safety, and clinical efficacy of CNA from a large, first-ever multicenter US registry.

Methods: A multicenter registry from 15 US sites was established by collecting data from consecutive patients undergoing CNA for recurrent VVS or symptomatic functional bradycardia (sinus bradycardia [SB] or atrioventricular block [AVB]) refractory to medical therapy and behavioral modification (2018-2024).

Results: A total of 205 patients who underwent 210 CNA procedures were included. The mean age was 47 ± 17 years, 49% were female, and baseline left ventricular ejection fraction was 60% ± 5%. The most common indication for CNA was syncope in 66.3% (VVS 61.5%, syncope related to AVB 4.9%), followed by SB in 31.2%, AVB in 1.5%, or both SB and AVB in 0.9%. An anatomical approach to target typical ganglionated plexus locations was implemented in all cases, with high-frequency stimulation in 47% of procedures. Endocardial ablation targeting ganglionated plexuses was performed in both atria in 77%, with 697 ± 515 seconds of radiofrequency application. Vagal and sympathetic responses during ablation were observed in 52% and 73% of cases, respectively. The mean increase in heart rate immediately after ablation was 20 ± 15 beats/min. Complications were observed in 4.7% of procedures: 2 respiratory failures requiring bilevel positive airway pressure, 1 right diaphragmatic paralysis, and 4 sinus node dysfunction, with a major adverse event rate of 1.4% (2 hemopericardium, 1 death). At a mean follow-up of 14 ± 11 months, 78% of patients with syncope remained free from recurrence, with a reduction in episodes from a median of 7 (4-15) episodes to a median of 0 (0-0) episodes. Overall, 97% of the cohort remained free from pacemaker implantation.

Conclusions: In the largest multicenter CNA experience to date, acceleration of baseline heart rate and a significant reduction in syncope burden were achieved with an acceptable rate of major procedural complications. These observational data pave the way for future randomized trials to evolve CNA indications beyond compassionate usage for managing functional bradycardia and reflex syncope.

Keywords: bradycardia; cardioneural ablation; syncope; vasovagal.

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Conflict of interest statement

Funding Support and Author Disclosures Dr Pujol-Lopez was funded through a Río Hortega contract CM22/00107 and M-AES MV23/00015 (Instituto de Salud Carlos III, Fondo Social Europeo). Dr Tung has received speaking fees and advisory board fees from Abbott, Biotronik, Boston Scientific, and Medtronic; and research grant support from Abbott. Dr Alyesh has received speaking fees, consulting, and advisory board fees from Abbott, Biosense Webster, and 3PH. Dr Gerstenfeld has received advisory board and lecture honoraria from Abbott, Biosense Webster, and Adagio Medical; and research grant and lecture honoraria from Abbott and Boston Scientific. Dr K. Kumar has received honoraria from Abbott (mapping/ablation technology) and Philips/Cardiologs (electrocardiogram interpretation). Dr Upadhyay has received speaking or consulting fees from Abbott, Biotronik, Boston Scientific, GE Medical, Medtronic, Philips, Rhythm Science, and Zoll Medical. Dr Pujol-Lopez has received speaker honoraria from Medtronic. Dr Sundaram is a patent holder on the Abbott Mapping system (unrelated to this topic); has speaker bureau and consulting agreements with Abbott, Boston Scientific, and Medtronic; and is an equity interest holder in and has received advisory board fees from Heart Hero (unrelated to this topic). Dr Aksu has received speaking fees and advisory board fees (Abbott). Dr Tzou has received speaking fees or advisory board fees from Abbott, the American Heart Association, the American College of Cardiology, Biosense Webster, Biotronik, Boston Scientific, Medtronic, and Pulsar; and research grant support from Biosense Webster, Abbott, and CardioNXT. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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