Cardiovascular Disease-Specific Responses to Autonomic Denervation.

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).