Cardiovascular Disease-Specific Responses to Autonomic Denervation.

Guannan Liu, Jikai Zhao, Praloy Chakraborty, Huishan Wang, Yuji Zhang, Fangran Xin, Dengshun Tao, Sunny S Po, Keyan Zhao, Zongtao Yin

Journal: JACC. Clinical electrophysiology 2025;11(4):776-788

PMID: 39846931

Abstract

BACKGROUND

Calcium-mediated autonomic denervation has been shown to suppress postoperative atrial fibrillation (POAF) after coronary artery bypass grafting.

OBJECTIVES

This study sought to evaluate whether similar autonomic denervation can prevent POAF after mitral or aortic valve surgeries.

METHODS

This research consisted of 2 single-center, randomized, double-blind, sham-controlled trials: CAP-AF2 (Calcium Autonomic Denervation Prevents Postoperative Atrial Fibrillation in Patients Undergoing Isolated Mitral Valve Surgery for Mitral Regurgitation) for mitral valve (MV) surgery and CAP-AF3 (Calcium Autonomic Denervation Prevents Postoperative Atrial Fibrillation in Patients Undergoing Isolated Aortic Valve Surgery) for aortic valve surgery. Patients were randomized to receive injections of either 5% CaCl or 0.9% NaCl (control) into the atrial ganglionated plexi during surgery. The primary outcome was the incidence of POAF ≥30 seconds within 7 days after surgery. Secondary outcomes included hospital stay, AF burden, actionable antiarrhythmic therapy for POAF, and inflammatory marker.

RESULTS

After 160 patients were enrolled into the CAP-AF2 trial, mid-term analysis revealed a significant increase in POAF incidence in the CaCl group (55.13%, CaCl vs 37.80%, NaCl; P = 0.028). The CAP-AF2 trial was terminated by the safety committee. In the CAP-AF3 trial, 239 patients were randomized; final analysis showed no significant difference in the POAF incidence between the CaCl and NaCl groups (35.59% vs 39.67%, P = 0.516). Postoperative hospital stay, AF burden, antiarrhythmic therapy for POAF, and plasma levels of inflammatory markers were not different between the 2 groups in both trials. Immunohistochemical analyses showed parasympathetic predominance at the tissue level in patients receiving MV surgery.

CONCLUSIONS

Calcium-mediated autonomic denervation did not uniformly prevent POAF across all cardiac surgeries, with an increased incidence observed in the MV surgery group, highlighting the need for disease-specific strategies to prevent POAF. (Calcium Autonomic Denervation Prevents Postoperative Atrial Fibrillation in Patients Undergoing Isolated Mitral Valve Surgery for Mitral Regurgitation [CAP-AF2]; ChiCTR2000029314; Calcium Autonomic Denervation Prevents Postoperative Atrial Fibrillation in Patients Undergoing Isolated Aortic Valve Surgery [CAP-AF3]; ChiCTR2000029313).

Copyright © 2025 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Address: Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China.; Section of Cardiovascular Diseases and Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. Electronic address: [email protected].; Section of Cardiovascular Diseases and Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.; Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China. Electronic address: [email protected].
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