Long-Term Suppression of Atrial Fibrillation by Botulinum Toxin Injection Into Epicardial Fat Pads in Patients Undergoing Cardiac Surgery

Abstract

Background-Animal models suggest that the neurotransmitter inhibitor, botulinum toxin, when injected into the epicardial fat pads can suppress atrial fibrillation inducibility. The aim of this prospective randomized double-blind study was to compare the efficacy and safety of botulinum toxin injection into epicardial fat pads for preventing atrial tachyarrhythmias. Methods and Results-Patients with history of paroxysmal atrial fibrillation and indication for coronary artery bypass graft surgery were randomized to botulinum toxin (Xeomin, Merz, Germany; 50 U/1 mL at each fat pad; n=30) or placebo (0.9% normal saline, 1 mL at each fat pad; n=30) injection into epicardial fat pads during surgery. Patients were followed for 1 year to assess maintenance of sinus rhythm using an implantable loop recorder. All patients in both groups had successful epicardial fat pad injections without complications. The incidence of early postoperative atrial fibrillation within 30 days after coronary artery bypass graft was 2 of 30 patients (7%) in the botulinum toxin group and 9 of 30 patients (30%) in the placebo group (P=0.024). Between 30 days and up to the 12-month follow-up examination, 7 of the 30 patients in the placebo group (27%) and none of the 30 patients in the botulinum toxin group (0%) had recurrent atrial fibrillation (P=0.002). There were no complications observed during the 1-year follow-up. Conclusions-Botulinum toxin injection into epicardial fat pads during coronary artery bypass graft provided substantial atrial tachyarrhythmia suppression both early as well as during 1-year follow-up, without any serious adverse events. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01842529.

Ganglionated plexi as neuromodulation targets for atrial fibrillation

“…Botulinum toxin injection in two fat pads suppressed AF inducibility at 1 week, but this disappeared at 2 weeks and 3 weeks. In human randomized clinical trials, however, botulinum toxin injected in the epicardial fat pads during cardiac surgery not only suppressed postoperative AF but also reduced the incidence of AF for at least 1 year . The prolonged benefit suggests that botulinum might induce GP remodeling.…”

Effect of botulinum toxin on inducibility and maintenance of atrial fibrillation in ovine myocardial tissue

“…showed that post‐CABG injection of BTX led to a decreased incidence of AF 30 days after surgery . More recently, the same group presented data showing that this difference was sustained for up to 1 year after surgery . The protective mechanism of BTX has been theorized to be due to its effects on acetylcholine release .…”

“…Finally, vulnerability to AF may not be reflected by programmed atrial stimulation. Although this may be debatable, studies have shown a correlation between AF inducibility using programmed atrial stimulation and the clinical burden of AF …”

“…Its mechanism of action is through the inhibition of acetylcholine release from axon endings . A recently reported 1‐year clinical study suggests that fat pad injection of BTX decreases the incidence of AF after coronary artery bypass grafting (CABG) …”

Highlights from Heart Rhythm Society 2017: Atrial Fibrillation

“…This would be reminiscent of data originally presented at the Annual Sessions in which the AF-free period after epicardial fat pad botulinum toxin injection in patients undergoing open heart surgery long outlasted the autonomic effects. 13 Conclusions AF has been a robust subject at many of the Heart Rhythm Sessions, and the 2017 Scientific Sessions were no exception. I hope these ''highlights,'' as subjective as they may be, spark a continuing interest in AF investigation, but more importantly, that they translate into improved care for our patients.…”