Botulinum toxin injection does not prevent postoperative AF: NOVA
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CHICAGO — Epicardial botulinum toxin type A injected into epicardial fat pads after cardiac surgery did not suppress incidence of postoperative atrial fibrillation compared with placebo, according to findings from the NOVA study.
Postoperative AF occurs in 30% to 60% of patients after cardiac surgery and the incidence has not changed over decades, Jonathan P. Piccini, MD, MHS, FAHA, FHRS, associate professor of medicine and director of cardiac electrophysiology at Duke University Medical Center and member in the Duke Clinical Research Institute, said during a late-breaking science presentation at the American Heart Association Scientific Sessions.
There are few effective and safe therapies for postoperative AF; only 70% of patients receive beta-blockers and often have them withdrawn after surgery, whereas postoperative AF is associated with increased risk for stroke, morbidity and mortality, as well as higher health care utilization costs, Piccini, a member of the Cardiology Today Editorial Board, said.
“There is a significant and unmet need for safe and effective treatments to prevent postoperative AF after cardiac surgery,” Piccini said.
In a phase 2, randomized, placebo-controlled trial, Piccini and colleagues analyzed data from 312 adults aged 55 to 90 years who underwent open-chest cardiac surgery and had normal sinus rhythm in the 48 hours before surgery. The mean age of participants was 67 years; 17% were women; 64% underwent isolated bypass surgery and 12% underwent combination bypass surgery and heart valve surgery. Researchers randomly assigned patients 125 U botulinum toxin type A, 250 U botulinum toxin type A or sham placebo after surgery. The primary endpoint was the percentage of patients with at least one continuous AF episode lasting at least 30 seconds. Secondary endpoints included AF burden, percent of participants with at least one event of symptomatic AF and time to first occurrence of AF.
In the placebo group, 46% of participants experienced an episode of postoperative AF lasting at least 30 seconds, compared with 47% in the 250 U botulinum toxin group (RR = 1.04; 95% CI, 0.79-1.37; P = .78) and 36% in the 125 U botulinum toxin group (RR = 0.8; 95% CI, 0.58-1.1; P = .16). In analyses stratified by age, there was a significant reduction in postoperative AF among participants aged 65 years and older treated with 125 U vs. placebo, as well as among participants who underwent bypass surgery and received the 125 U dose, Piccini said.
There was no difference in mean length of hospital stay between groups; however, all-cause rehospitalization during the first 30 days after discharge was numerically lower among participants treated with botulinum toxin vs. placebo, Piccini said. Adverse events were similar across treatment groups.
“Subgroup analyses do suggest a lower rate of postoperative AF and rehospitalization in participants who underwent isolated bypass surgery and in those age 65 years and older who received 125 U of botulinum toxin type A,” Piccini said. “Suppression of AF with botulinum toxin is likely mediated through both direct autonomic effects as well as reductions in inflammation.”
Discussing the NOVA findings, Usha B. Tedrow, MD, MS, FHRS, director of the clinical cardiac electrophysiology fellowship program and clinical director of the ventricular arrhythmia program at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School, noted that reductions in AF incidence were only seen among participants who received the 125 U dose, raising questions about the mechanism of reductions in AF.
“The numbers are small, so subgroups are appropriately interpreted with caution,” Tedrow said. “It would be very interesting to know the results of heart rate variability of other autonomic assessment in the groups to try to better elucidate the mechanism of action of botulinum toxin in these patients.”
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Piccini JP, et al. LBS.08: Treating atrial and supraventricular arrhythmias. Presented at: American Heart Association Scientific Sessions; Nov. 5-7, 2022; Chicago (hybrid meeting).
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