Botulinum Toxin Injection in Epicardial Fat Pads Can Prevent Recurrences of Atrial Fibrillation After Cardiac Surgery

Pokushalov, Evgeny; Kozlov, B. N.; Romanov, Alexander; Стрельников, А. Г.; Bayramova, Sevda; Sergeevichev, David; Bogachev-Prokophiev, Alexander; Железнев, С. И.; Shipulin, V. M.; Salakhutdinov, N. F.; Lomivorotov, Vladimir V.; Karaskov, Alexander; Po, Sunny S.; Steinberg, Jonathan S.

doi:10.1016/j.jacc.2014.04.062

Cited by 70 publications

(49 citation statements)

References 2 publications

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“…22, 23 Another randomized trial showed that botulinum toxin injection in epicardial fat pads can prevent recurrences of AF after cardiac surgery. 24 While epicardial fat pad ablation does not have long-term effects in animal models, 25 the same group of authors have later concluded that extensively ablating LA covering GP areas along with pulmonary vein antrum isolation enhanced the denervation of autonomic nerve system and seemed to improve procedural outcome in patients with AF. 26 …”

Section: Discussionmentioning

confidence: 99%

Skin sympathetic nerve activity precedes the onset and termination of paroxysmal atrial tachycardia and fibrillation

et al. 2017

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Background Skin sympathetic nerve activity (SKNA) is useful in estimating sympathetic tone in humans Objective To test the hypothesis that (1) increased SKNA is associated with the onset and termination of paroxysmal atrial tachycardia (AT) and AF and (2) The sinoatrial node (SAN) response to SKNA is reduced in patients with more frequent of AT or AF. Methods SKNA and electrocardiogram were recorded in 11 patients (4 males and 7 females, average age 66±10 years), including 3 patients with AT (11±18 episodes/patient) and 8 patients with AF (24±26 episodes/patient). Results The average SKNA (aSKNA, in μV) 10 s prior to AT onset were 1.07±0.10; 10 s after termination were 1.27±0.10, both were significantly (p=0.032, p<0.0001) higher than that during sinus rhythm (0.97±0.09). The aSKNA 10 s prior to AF onset were 1.34±0.07 and 10 s after termination were 1.31±0.07. Both were significantly (p<0.0001) higher than that during sinus rhythm (1.04±0.07). The aSKNA before onset (p<0.0001) and after termination (p= 0.0011) were both higher in AF than in AT. The sinus rate correlated (p<0.0001) with aSKNA in each patient (average r: 0.74, 95% confidence interval (CI): 0.65–0.84). The r in each patient negatively correlated with the number of AT and AF episodes (r= − 0.6493, 95% confidence interval: −0.8990 to −0.08073, p=0.0306). Conclusions Increased SKNA was observed both at onset and termination of AT and AF. The patients with more frequent AT and AF episodes had less of a correlation between sinus rate and aSKNA, suggesting SAN remodeling by tachycardia.

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Section: Discussionmentioning

confidence: 99%

Skin sympathetic nerve activity precedes the onset and termination of paroxysmal atrial tachycardia and fibrillation

et al. 2017

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“…In addition, the mechanisms of postoperative AF may be more complex and are not entirely dependent on the presence of abnormal autonomic nerve activities. 19 A more recent study 20 shows that botulinum toxin injection into epicardial fat pads during coronary artery bypass graft surgery provided substantial suppression of atrial tachyarrhythmias postoperatively. These findings suggest that increased burst ICNA discharges maybe causally related to the development of postoperative atrial arrhythmias, including AF.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous recordings of intrinsic cardiac nerve activity and skin sympathetic nerve activity from human patients during the postoperative period

et al. 2017

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Background Intrinsic cardiac nerve activities (ICNA) and the skin nerve activities (SKNA) are both associated with cardiac arrhythmias in dogs. Objective To test the hypothesis that ICNA and SKNA correlate with postoperative cardiac arrhythmias in humans. Methods Eleven patients (60±13 years old; 4 female) were enrolled in this study. Electrical signals were simultaneously recorded from electrocardiogram (ECG) patch electrodes on the chest wall and from two temporary pacing wires placed during open heart surgery on the left atrial epicardial fat pad. The signals were filtered to display SKNA and ICNA. Premature atrial contractions (PAC) and premature ventricular contractions (PVC) were manually determined. The SKNA and ICNA of the first 300 min of each patient were calculated min-by-min to determine baseline average amplitudes of nerve activities and to determine their correlation with arrhythmia burden. Results We processed 1365±973 min of recording per patient. Low-amplitude SKNA and ICNA were present at all time, while the burst discharges were observed much less frequently. Both SKNA and burst ICNA were significantly associated with the onset of PACs and PVCs. Baseline average ICNA (aICNA), but not SKNA (aSKNA), had a significant association with PAC burden. The correlation coefficient (r) between aICNA and PAC burden was 0.78 (P<0.01). A patient with the greatest aICNA developed postoperative atrial fibrillation. Conclusions ICNA and SKNA can be recorded from human patients in the postoperative period. Baseline magnitude of ICNA correlates with PAC burden and development of postoperative atrial fibrillation.

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“…36 Briefly, this was a randomized, double-blind, parallel-group, 2-center study that compared treatment with botulinum toxin to normal saline (placebo). The study protocol was approved by the local Ethics Committee and conducted in compliance with the protocol, and in accordance with standard institutional operating procedures and the Declaration of Helsinki.…”

Section: Methodsmentioning

confidence: 99%

“…This study demonstrated that botulinum toxin injection substantial suppressed postoperative atrial tachyarrhythmias during the first postoperative month after CABG without any serious adverse events. 36 We hypothesized that by suppression of the ganglionated plexi (GP) activity in the epicardial fat pads, longer term antiarrhythmic effects can be achieved.…”

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confidence: 99%

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

Pokushalov

Kozlov

Romanov

et al. 2015

Circ: Arrhythmia and Electrophysiology

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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.

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Botulinum Toxin Injection in Epicardial Fat Pads Can Prevent Recurrences of Atrial Fibrillation After Cardiac Surgery

Cited by 70 publications

References 2 publications

Skin sympathetic nerve activity precedes the onset and termination of paroxysmal atrial tachycardia and fibrillation

Skin sympathetic nerve activity precedes the onset and termination of paroxysmal atrial tachycardia and fibrillation

Simultaneous recordings of intrinsic cardiac nerve activity and skin sympathetic nerve activity from human patients during the postoperative period

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

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