Meeting News CoveragePerspective

Botulinum toxin injection during CABG suppresses AF for 1 year

BOSTON — Injection of botulinum toxin into epicardial fat pads during CABG reduced the incidence of postoperative atrial fibrillation and suppressed recurrent atrial fibrillation for 1 year, according to findings presented at the Heart Rhythm Society Annual Scientific Sessions.

Researchers randomly assigned 60 patients with paroxysmal AF and an indication for CABG to an injection of botulinum toxin (Xeomin, Merz Pharmaceuticals) 50 U/1 mL at each fat pad or placebo (0.9% normal saline, 1 mL at each fat pad) during surgery.

Evgeny Pokushalov, MD, PhD

Evgeny Pokushalov

“These patients have 10% to 50% [AF] recurrence,” Evgeny Pokushalov, MD, PhD, from State Research Institute of Circulation Pathology, Novosibirsk, Russia, said during a press conference.

He said some AF recurrences after CABG are explained by neurotransmitters related to the epicardial fat pads, and botulinum toxin in animal studies was shown to inhibit neurotransmitters and suppress AF.

Patients were followed for 1 year to assess maintenance of sinus rhythm using an implantable loop recorder.

The researchers previously reported that, at 30 days, AF recurred in 7% of the botulinum toxin group compared with 30% of the control group (P = .024).

However, from 30 days to 1 year, no patients in the botulinum toxin group had recurrent AF compared with 27% of the control group (P = .002), Pokushalov said. Of the controls, two evolved to persistent AF and required catheter ablation.

At 1-year follow-up, mean AF burden according to the implantable loop recorder was 0.07% in the botulinum toxin group compared with 1.5% in the control group (P < .001), the researchers found.

There were no strokes or other serious clinical events observed in either group.

“Injection of botulinum toxin ruins the vicious cycle [of neurotransmitters and AF], and the patient has enough time for reverse remodeling,” Pokushalov said. “Most important, the injection is safe. Before the surgery, we cannot predict who will have recurrent AF, so this can be a prophylactic.” – by Erik Swain

Reference:

Pokushalov E, et al. Abstract LBCT01-04. Presented at: Heart Rhythm Society Annual Scientific Sessions; May 13-16, 2015; Boston.

Disclosure: Pokushalov reports speaking for Biosense Webster, Boston Scientific and Medtronic.

BOSTON — Injection of botulinum toxin into epicardial fat pads during CABG reduced the incidence of postoperative atrial fibrillation and suppressed recurrent atrial fibrillation for 1 year, according to findings presented at the Heart Rhythm Society Annual Scientific Sessions.

Researchers randomly assigned 60 patients with paroxysmal AF and an indication for CABG to an injection of botulinum toxin (Xeomin, Merz Pharmaceuticals) 50 U/1 mL at each fat pad or placebo (0.9% normal saline, 1 mL at each fat pad) during surgery.

Evgeny Pokushalov, MD, PhD

Evgeny Pokushalov

“These patients have 10% to 50% [AF] recurrence,” Evgeny Pokushalov, MD, PhD, from State Research Institute of Circulation Pathology, Novosibirsk, Russia, said during a press conference.

He said some AF recurrences after CABG are explained by neurotransmitters related to the epicardial fat pads, and botulinum toxin in animal studies was shown to inhibit neurotransmitters and suppress AF.

Patients were followed for 1 year to assess maintenance of sinus rhythm using an implantable loop recorder.

The researchers previously reported that, at 30 days, AF recurred in 7% of the botulinum toxin group compared with 30% of the control group (P = .024).

However, from 30 days to 1 year, no patients in the botulinum toxin group had recurrent AF compared with 27% of the control group (P = .002), Pokushalov said. Of the controls, two evolved to persistent AF and required catheter ablation.

At 1-year follow-up, mean AF burden according to the implantable loop recorder was 0.07% in the botulinum toxin group compared with 1.5% in the control group (P < .001), the researchers found.

There were no strokes or other serious clinical events observed in either group.

“Injection of botulinum toxin ruins the vicious cycle [of neurotransmitters and AF], and the patient has enough time for reverse remodeling,” Pokushalov said. “Most important, the injection is safe. Before the surgery, we cannot predict who will have recurrent AF, so this can be a prophylactic.” – by Erik Swain

Reference:

Pokushalov E, et al. Abstract LBCT01-04. Presented at: Heart Rhythm Society Annual Scientific Sessions; May 13-16, 2015; Boston.

Disclosure: Pokushalov reports speaking for Biosense Webster, Boston Scientific and Medtronic.

    Perspective
    Jonathan R. Kaltman, MD

    Jonathan M. Kalman

    • The major implication of this study is the mechanism of AF. It tells us about the importance of the autonomic nervous system in the initiation of, at least, postsurgical AF. I’m not sure how well that will translate to patients who aren’t undergoing surgery who have AF. It’s an open question. If this translates well in a multicenter study, then it can save hospital stays and save complications for patients who develop AF in the postoperative setting.

      • Jonathan M. Kalman, MBBS, FRACP, PhD, FACC, FHRS
      • Professor of Medicine, University of Melbourne
        Director of Cardiac Electrophysiology, Royal Melbourne Hospital
        Melbourne, Australia
    • Disclosures: Kalman reports no relevant financial disclosures.
    Perspective
    John D. Day MD, FHRS, FACC

    John D. Day

    • This was a very well-done pilot study. It was not surprising that botulinum toxin helped in the early postoperative state. We know that the autonomic nervous system does play a role in post-operative AF. We also know that there are ganglionic plexi and other nerves within the fat pads. What was surprising was that by 6 months after the surgery, the heart rate variability had returned to baseline levels, an indication that there was no longer an effect of botulinum toxin, but yet there was no AF from months 6 to 12.

      Although this was a small study, we have never seen a study with 100% elimination of AF. Also, with the effects of botulinum toxin gone by 6 months, it raises the question as to whether there was “autonomic retraining,” accounting for complete elimination of AF as measured by an implantable loop recorder.

      This has profound implications. It challenges our whole paradigm of AF and gets into the issue of neuromodulation, the brain-heart connection. Could it be that neuromodulation is more important in eliminating AF than the traditional pulmonary vein isolation?

      Based on the findings of this study, the question that naturally arises is can the same results be obtained differently?  For example, Prash Sanders, MBBS, PhD, and colleagues have shown that the amount of pericardial fat predicts AF (Wong CX, et al. J Am Coll Cardiol. 2011;doi:10.1016/j.jacc.2010.11.045). Perhaps the reason why weight loss reduces AF is because pericardial fat is reduced.

      Alternatively, perhaps there are other ways to achieve neuromodulation.  For example, perhaps the reason why transplanted hearts don’t get AF is because they are denervated. Consider also a study conducted by Dhanunjaya Lakireddy, MD, FACC, FHRS, and colleagues on yoga and AF (J Am Coll Cardiol. 2013;doi:10.1016/j.jacc.2012.11.060). Yoga was associated with a profound drop in AF. Are yoga, meditation, etc. really forms of neuromodulation? 

       I realize this is just a small, early study, but I am fascinated by the data and there are profound implications. Maybe all of these things tie in through a pericardial fat or neuromodulation effect. 

      • John D. Day, MD, FHRS, FACC
      • Director of Heart Rhythm Services
        Intermountain Heart Institute, Murray, Utah
        President, Heart Rhythm Society
    • Disclosures: Day reports no relevant financial disclosures.

    See more from Heart Rhythm Society Scientific Sessions