Long-Term Suppression of Atrial Fibrillation by Botulinum Toxin Injection Into Epicardial Fat Pads in Patients Undergoing Cardiac Surgery: One-Year Follow-Up of a Randomized Pilot Study.
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.


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.


BACKGROUND
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01842529.
From the State Research Institute of Circulation Pathology, Novosibirsk, Russia (E.P., A.R., A.S., S.B., D.S., A.B.-P., S.Z., V.V.L., A.K.); Institute of Cardiology, Siberian Division of Russian Academy of Medical Sciences, Tomsk, Russia (B.K., V.S.); Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City (S.S.P.); and University of Rochester School of Medicine & Dentistry and the Arrhythmia Institute, The Valley Health System, New York, NY and Ridgewood, NJ (J.S.S.).
Evgeny
E
Pokushalov
From the State Research Institute of Circulation Pathology, Novosibirsk, Russia (E.P., A.R., A.S., S.B., D.S., A.B.-P., S.Z., V.V.L., A.K.); Institute of Cardiology, Siberian Division of Russian Academy of Medical Sciences, Tomsk, Russia (B.K., V.S.); Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City (S.S.P.); and University of Rochester School of Medicine & Dentistry and the Arrhythmia Institute, The Valley Health System, New York, NY and Ridgewood, NJ (J.S.S.).
Boris
B
Kozlov
From the State Research Institute of Circulation Pathology, Novosibirsk, Russia (E.P., A.R., A.S., S.B., D.S., A.B.-P., S.Z., V.V.L., A.K.); Institute of Cardiology, Siberian Division of Russian Academy of Medical Sciences, Tomsk, Russia (B.K., V.S.); Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City (S.S.P.); and University of Rochester School of Medicine & Dentistry and the Arrhythmia Institute, The Valley Health System, New York, NY and Ridgewood, NJ (J.S.S.).
Alexander
A
Romanov
From the State Research Institute of Circulation Pathology, Novosibirsk, Russia (E.P., A.R., A.S., S.B., D.S., A.B.-P., S.Z., V.V.L., A.K.); Institute of Cardiology, Siberian Division of Russian Academy of Medical Sciences, Tomsk, Russia (B.K., V.S.); Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City (S.S.P.); and University of Rochester School of Medicine & Dentistry and the Arrhythmia Institute, The Valley Health System, New York, NY and Ridgewood, NJ (J.S.S.).
Artem
A
Strelnikov
From the State Research Institute of Circulation Pathology, Novosibirsk, Russia (E.P., A.R., A.S., S.B., D.S., A.B.-P., S.Z., V.V.L., A.K.); Institute of Cardiology, Siberian Division of Russian Academy of Medical Sciences, Tomsk, Russia (B.K., V.S.); Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City (S.S.P.); and University of Rochester School of Medicine & Dentistry and the Arrhythmia Institute, The Valley Health System, New York, NY and Ridgewood, NJ (J.S.S.).
Sevda
S
Bayramova
From the State Research Institute of Circulation Pathology, Novosibirsk, Russia (E.P., A.R., A.S., S.B., D.S., A.B.-P., S.Z., V.V.L., A.K.); Institute of Cardiology, Siberian Division of Russian Academy of Medical Sciences, Tomsk, Russia (B.K., V.S.); Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City (S.S.P.); and University of Rochester School of Medicine & Dentistry and the Arrhythmia Institute, The Valley Health System, New York, NY and Ridgewood, NJ (J.S.S.).
David
D
Sergeevichev
From the State Research Institute of Circulation Pathology, Novosibirsk, Russia (E.P., A.R., A.S., S.B., D.S., A.B.-P., S.Z., V.V.L., A.K.); Institute of Cardiology, Siberian Division of Russian Academy of Medical Sciences, Tomsk, Russia (B.K., V.S.); Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City (S.S.P.); and University of Rochester School of Medicine & Dentistry and the Arrhythmia Institute, The Valley Health System, New York, NY and Ridgewood, NJ (J.S.S.).
Alexander
A
Bogachev-Prokophiev
From the State Research Institute of Circulation Pathology, Novosibirsk, Russia (E.P., A.R., A.S., S.B., D.S., A.B.-P., S.Z., V.V.L., A.K.); Institute of Cardiology, Siberian Division of Russian Academy of Medical Sciences, Tomsk, Russia (B.K., V.S.); Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City (S.S.P.); and University of Rochester School of Medicine & Dentistry and the Arrhythmia Institute, The Valley Health System, New York, NY and Ridgewood, NJ (J.S.S.).
Sergey
S
Zheleznev
From the State Research Institute of Circulation Pathology, Novosibirsk, Russia (E.P., A.R., A.S., S.B., D.S., A.B.-P., S.Z., V.V.L., A.K.); Institute of Cardiology, Siberian Division of Russian Academy of Medical Sciences, Tomsk, Russia (B.K., V.S.); Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City (S.S.P.); and University of Rochester School of Medicine & Dentistry and the Arrhythmia Institute, The Valley Health System, New York, NY and Ridgewood, NJ (J.S.S.).
Vladimir
V
Shipulin
From the State Research Institute of Circulation Pathology, Novosibirsk, Russia (E.P., A.R., A.S., S.B., D.S., A.B.-P., S.Z., V.V.L., A.K.); Institute of Cardiology, Siberian Division of Russian Academy of Medical Sciences, Tomsk, Russia (B.K., V.S.); Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City (S.S.P.); and University of Rochester School of Medicine & Dentistry and the Arrhythmia Institute, The Valley Health System, New York, NY and Ridgewood, NJ (J.S.S.).
Vladimir V
VV
Lomivorotov
From the State Research Institute of Circulation Pathology, Novosibirsk, Russia (E.P., A.R., A.S., S.B., D.S., A.B.-P., S.Z., V.V.L., A.K.); Institute of Cardiology, Siberian Division of Russian Academy of Medical Sciences, Tomsk, Russia (B.K., V.S.); Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City (S.S.P.); and University of Rochester School of Medicine & Dentistry and the Arrhythmia Institute, The Valley Health System, New York, NY and Ridgewood, NJ (J.S.S.).
Alexander
A
Karaskov
From the State Research Institute of Circulation Pathology, Novosibirsk, Russia (E.P., A.R., A.S., S.B., D.S., A.B.-P., S.Z., V.V.L., A.K.); Institute of Cardiology, Siberian Division of Russian Academy of Medical Sciences, Tomsk, Russia (B.K., V.S.); Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City (S.S.P.); and University of Rochester School of Medicine & Dentistry and the Arrhythmia Institute, The Valley Health System, New York, NY and Ridgewood, NJ (J.S.S.).
Sunny S
SS
Po
From the State Research Institute of Circulation Pathology, Novosibirsk, Russia (E.P., A.R., A.S., S.B., D.S., A.B.-P., S.Z., V.V.L., A.K.); Institute of Cardiology, Siberian Division of Russian Academy of Medical Sciences, Tomsk, Russia (B.K., V.S.); Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City (S.S.P.); and University of Rochester School of Medicine & Dentistry and the Arrhythmia Institute, The Valley Health System, New York, NY and Ridgewood, NJ (J.S.S.). steijo@valleyhealth.com.
Jonathan S
JS
Steinberg
D000273:Adipose Tissue; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage* / Q000009:adverse effects; D001026:Coronary Artery Bypass / Q000009:adverse effects; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000601:surgery*; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007267:Injections; D007430:Intraoperative Care; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome
D000889:Anti-Arrhythmia Agents; D019274:Botulinum Toxins, Type A; C545476:incobotulinumtoxinA
atrial fibrillation; autonomic nervous system; botulinum toxins; coronary artery bypass; tachycardia