Temporary autonomic modulation with botulinum toxin type A to reduce atrial fibrillation after cardiac surgery.

Journal Article (Journal Article;Multicenter Study)

BACKGROUND: Postoperative atrial fibrillation (POAF) frequently complicates cardiac surgery and is associated with worse outcomes. The cardiac autonomic nervous system is implicated in the pathogenesis of POAF. OBJECTIVE: The purpose of this study was to determine the efficacy and safety of selective cardiac autonomic modulation in preventing POAF. METHODS: In this randomized, double-blind, placebo-controlled trial, adults undergoing cardiac surgery were randomized 1:1 to intraoperative injection of 250 units onabotulinumtoxinA (botulinum toxin type A [BoNTA]) or placebo into epicardial fat pads. The study was powered to detect a 40% reduction in relative risk of POAF. Time to first episode of in-hospital POAF was the primary outcome, evaluated in patients receiving injection. Additionally, incidence of POAF, length of stay (LOS), and adverse events were examined. RESULTS: The trial assigned 145 patients to injection, 15 of whom were dropped before treatment, leaving 130 patients for analysis. Overall, 36.5% (23/63) of BoNTA-treated patients developed POAF compared with 47.8% (32/67) of placebo-treated patients. The time-to-event analysis revealed a hazard ratio of 0.69 (95% confidence interval 0.41-1.19; P = .18) for the BoNTA vs placebo arm. There were no significant differences in postoperative hospital LOS (median [interquartile range] 6.0 [3.4] vs 6.2 [3.7] days; P = .51) or adverse events prolonging LOS (27/63 [42.9%] vs 30/67 [44.8%]; P = .83) in patients receiving BoNTA vs placebo. CONCLUSION: Epicardial injection of onabotulinumtoxinA was without discernible adverse effects, but we failed to detect a significant difference in risk of POAF. Future large-scale studies of epicardial onabotulinumtoxinA injection as a potential POAF prevention strategy should be designed to study smaller, but clinically meaningful, treatment effects.

Full Text

Duke Authors

Cited Authors

  • Waldron, NH; Cooter, M; Haney, JC; Schroder, JN; Gaca, JG; Lin, SS; Sigurdsson, MI; Fudim, M; Podgoreanu, MV; Stafford-Smith, M; Milano, CA; Piccini, JP; Mathew, JP

Published Date

  • February 2019

Published In

Volume / Issue

  • 16 / 2

Start / End Page

  • 178 - 184

PubMed ID

  • 30414840

Electronic International Standard Serial Number (EISSN)

  • 1556-3871

Digital Object Identifier (DOI)

  • 10.1016/j.hrthm.2018.08.021


  • eng

Conference Location

  • United States