Temporary autonomic modulation with botulinum toxin type A to reduce atrial fibrillation after cardiac surgery.
Aged
Atrial Fibrillation
/ diet therapy
Autonomic Nervous System
/ drug effects
Botulinum Toxins, Type A
/ administration & dosage
Cardiac Surgical Procedures
/ adverse effects
Double-Blind Method
Female
Follow-Up Studies
Humans
Male
Neurotoxins
/ administration & dosage
Postoperative Complications
/ drug therapy
Time Factors
Treatment Outcome
Atrial fibrillation
Autonomic modulation
Cardiac surgery
Neurocardiology
Postoperative atrial fibrillation
Journal
Heart rhythm
ISSN: 1556-3871
Titre abrégé: Heart Rhythm
Pays: United States
ID NLM: 101200317
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
29
05
2018
pubmed:
12
11
2018
medline:
3
10
2020
entrez:
12
11
2018
Statut:
ppublish
Résumé
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. The purpose of this study was to determine the efficacy and safety of selective cardiac autonomic modulation in preventing POAF. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 30414840
pii: S1547-5271(18)30822-1
doi: 10.1016/j.hrthm.2018.08.021
pii:
doi:
Substances chimiques
Neurotoxins
0
Botulinum Toxins, Type A
EC 3.4.24.69
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
178-184Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.