Calcium-Induced Autonomic Denervation in Patients With Post-Operative Atrial Fibrillation

J Am Coll Cardiol. 2021 Jan 5;77(1):57-67. doi: 10.1016/j.jacc.2020.10.049.

Abstract

Background: Post-operative atrial fibrillation (POAF) is associated with worse long-term cardiovascular outcomes.

Objectives: This study hypothesized that injecting calcium chloride (CaCl2) into the major atrial ganglionated plexi (GPs) during isolated coronary artery bypass grafting (CABG) can reduce the incidence of POAF by calcium-induced autonomic neurotoxicity.

Methods: This proof-of-concept study randomized 200 patients undergoing isolated, off-pump CABG to CaCl2 (n = 100) or sodium chloride (sham, n = 100) injection. Two milliliters of CaCl2 (5%) or sodium chloride (0.9%) was injected into the 4 major atrial GPs during CABG. All patients received 7-day continuous telemetry and Holter monitoring. The primary outcome was incidence of POAF (≥30 s) in 7 days. Secondary outcomes included length of hospitalization, POAF burden, average ventricular rate during AF, plasma level of inflammatory markers, and actionable antiarrhythmic therapy to treat POAF.

Results: The POAF incidence was reduced from 36% to 15% (hazard ratio: 0.366; 95% confidence interval: 0.211 to 0.635; p = 0.001). Length of hospitalization did not differ between the 2 groups. POAF burden (first 7 post-operative days), the use of amiodarone or esmolol, and the incidence of atrial couplets and nonsustained atrial tachyarrhythmias were significantly reduced in the CaCl2 group. Heart rate variability data showed a decrease in both high-frequency and low-frequency power in the CaCl2 group with a preserved low-frequency/high-frequency ratio, suggesting that the sympathetic/parasympathetic balance was not perturbed by CaCl2 injection.

Conclusions: Injection of CaCl2 into the 4 major atrial GPs reduced the POAF hazard by 63%. Inhibition of GP function by Ca-mediated neurotoxicity may underlie the therapeutic effect. (Calcium Autonomic Denervation Prevents Postoperative Atrial Fibrillation; ChiCTR1800019276).

Keywords: autonomic nervous system; calcium-mediated neurotoxicity; ganglionated plexi; post-operative atrial fibrillation.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amiodarone / therapeutic use
  • Anti-Arrhythmia Agents / therapeutic use
  • Atrial Fibrillation / prevention & control*
  • Autonomic Denervation*
  • Calcium Chloride / administration & dosage*
  • Coronary Artery Bypass*
  • Double-Blind Method
  • Drug Utilization / statistics & numerical data
  • Female
  • Heart Conduction System
  • Humans
  • Injections
  • Male
  • Middle Aged
  • Postoperative Complications / prevention & control*
  • Proof of Concept Study
  • Propanolamines / therapeutic use

Substances

  • Anti-Arrhythmia Agents
  • Propanolamines
  • Calcium Chloride
  • esmolol
  • Amiodarone

Associated data

  • ChiCTR/ChiCTR1800019276