TNT-POAF: Botulinum toxin may reduce postoperative AF

Issue: December 2017

ANAHEIM, Calif. — Epicardial fat pad injections of botulinum toxin may be a safe way to reduce postoperative atrial fibrillation without increasing adverse events after cardiac surgery, according to the results of the TNT-POAF study presented at the American Heart Association Scientific Sessions.

Perspective from Renate B. Schnabel, MD, MSc

“Postoperative AF is the most common complication after cardiac surgery and is unfortunately one that is associated with postoperative morbidity, increased length of stay in the ICU in the hospital and short and long-term mortality,” Nathan H. Waldron, MD, MHSc, from Duke University Medical Center, said during his presentation. “Cardiac autonomic dysregulation has consistently been linked with the development of AF and the clinical strategies to modulate the intrinsic cardiac autonomous nervous system met some preliminary success in reducing AF.”

With this preliminary success in mind, Waldron and colleagues conducted a double-blind randomized controlled trial to evaluate the efficacy and safety of epicardial botulinum toxin injection to reduce postoperative AF.

Botulinum toxin is also used for facial injections and to treat muscle stiffness/spasms and migraines.

According to Waldron, patients undergoing CABG, valve surgery or CABG plus valve surgery underwent 1:1 randomization to either injection of botulinum toxin or normal saline in five epicardial fat pads. Providers and research staff were also blinded to treatment assignment.

The primary outcomes were time to onset of first postoperative AF episode, both unadjusted and adjusted for various risk factors to account for baseline differences between the groups.

Key secondary outcomes were the occurrence of postoperative AF, burden of in-hospital postoperative AF, ICU, length of hospital stay and postoperative adverse events

Time to onset of first postoperative AF episode did not differ between groups, either in unadjusted (HR = 0.69; 95% CI, 0.4-1.18) or adjusted (HR = 0.7; 95% CI, 0.41-1.21) analyses, Waldron said.

Duration of first episode was shorter in those assigned botulinum toxin (1.9 hours vs. 5.5 hours; P = .01), but there was no difference in the other key secondary outcomes, according to the researchers.

While there was no significant difference in the incidence of postoperative AF between groups, Waldon said it was 11% lower in patients receiving epicardial botulinum toxin.

Limitations include the enrollment of high-risk, heterogeneous cardiac surgical patients at a single academic institution and the inability to detect smaller, but potentially clinically significant reductions in the risk of post-operative AF, he said.

“Epicardial botulinum toxin may be a safe way to reduce postoperative AF, but warrants further study in larger scale clinical trials,” Waldon concluded. – by Dave Quaile

Reference:

Waldon N. LBS.07. Innovative Therapies and Novel Applications. Presented at: American Heart Association Scientific Sessions; Nov. 11-15, 2017; Anaheim, California.

Disclosure: Waldron reports no relevant financial disclosures.

Perspective

Renate B. Schnabel, MD, MSc

The possibility of AF is an important health issue after major surgery. Drug prevention has so far been largely ineffective except for amiodarone, which is not routinely used due to its many side effects, so we need new concepts.

One new approach that has been around for the last couple of years is the temporary blockage of the dense autonomic denervation of the heart and by injecting the epicardial fat pads, we're trying to at least temporarily reduce autonomic denervation.

This concept has been proven to be possibly effective in a smaller study in individuals with postoperative AF where it could clearly be demonstrated that the AF burden can be reduced not only in the immediate postoperative, but also during long term over 12 months.

The hypothesis in this study now was that through the injection of neurotoxin, the incidence of the timed first incidence of AF in the post-operative period could be reduced.

Actually, what the authors saw was an 11% absolute risk reduction, which did not reach statistical significance, however, the study was very optimistically powered for 40% risk reduction.

Out of 2,017 patients screened for this procedure, only 130 (6.4%) were finally treated, which means that there could be bias. For example, there are strict exclusions such as hepatic and renal failure and left ventricular ejection fraction below 25%, and these are common characteristics in patients that undergo cardiac surgery.

There's also, as outlined by the authors, a possible imbalance in the baseline variables. For example, a higher rate of ACE inhibitor treatment in the control group and more individuals with a history of MI in the intervention group.

Overall, there was high beta-blocker and statin use compared to other studies. Prior AF has been permitted and may have diluted the results and unfortunately, we did not observe any statistically nor numerically or clinically relevant numbers for the outcomes the authors presented.

Presently, this study does not help us to understand the mechanisms underlying the nature of this increased risk of AF in a postoperative period.

However, I think this study gives us a concept of the role of autonomic imbalance, particularly parasympathetic activation in postoperative AF. The authors show that it might be a safe procedure and I hope that the absence of side effects does not mean the absence of a main effect. We have a transient effect on the suppression of AF as seen in other studies and it's a non-destructive procedure. On the other hand, we have to realize that patients who develop postoperative AF are in the long run at high risk for developing AF, so we might need more sustainable procedures to finally prevent incidence of AF. At present, I very much like the concept and I think that the authors presented a promising, innovative way of possibly reducing postoperative AF burden. I'm looking forward to more results from this group and maybe more explosive results.

Renate B. Schnabel, MD, MSc

Professor of Medicine

Universitätsklinikum Hamburg-Eppendorf

Disclosures: Schnabel reports no relevant financial disclosures.

American Heart Association

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TNT-POAF: Botulinum toxin may reduce postoperative AF

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