Long-term suppression of atrial fibrillation by botulinum toxin injection into epicardial fat pads in patients undergoing cardiac surgery: Three-year follow-up of a randomized study

Romanov, Alexander; Pokushalov, Evgeny; Ponomarev, Dmitry; Bayramova, Sevda; Шабанов, В. В.; Losik, Denis; Стенин, И. Г.; Елесин, Д. А.; Mikheenko, I.; Стрельников, А. Г.; Sergeevichev, David; Kozlov, B. N.; Po, Sunny S.; Steinberg, Jonathan S.

doi:10.1016/j.hrthm.2018.08.019

Cited by 88 publications

(66 citation statements)

References 20 publications

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“…Meanwhile physicians from diverse specialties are integrating botulinum toxin injections into their practices ranging from the treatment of incontinence, pain, headache, and hyperhidrosis [1] to the reduction of postoperative complications e.g. in cardiac surgery [2]. But the general popularity of BoNT was reached mainly after BoNT was used for cosmetic indications.…”

Section: Introductionmentioning

confidence: 99%

Effective long-term treatment with incobotulinumtoxin (Xeomin®) without neutralizing antibody induction: a monocentric, cross-sectional study

et al. 2020

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Background Among the spectrum of licensed botulinum neurotoxin preparations incobotulinumtoxin (incoBoNT/A; Xeomin®) is the only one which does not contain complex proteins. Therefore, incoBoNT/A has been suggested to have a low antigenicity, but precise estimations on incidence and prevalence of neutralizing antibody formation during long-term treatment are outstanding so far. Methods For the present cross-sectional study, 59 patients having exclusively been treated with incoBoNT/A (mono group) and 32 patients having been treated with other BoNT/A preparations less than nine times and who were then switched to at least 14 sessions of incoBoNT/A treatment (switch group) were recruited from one botulinum toxin outpatient clinic. Side effects and doses were extracted from the charts, and the efficacy of treatment was assessed by the patients using a visual analogue scale (0-100). The prevalence of neutralizing antibodies was tested by means of the mouse hemi-diaphragm assay (MHDA). Findings None of the patients in the mono and only two in the switch group had a positive MHDA-test. Across all indications and patients, mean improvement exceeded 67%. Improvement did not depend on age at onset, sex, change of dose or duration of treatment, but on disease entity. In patients with cervical dystonia, improvement was about the same in the mono and switch subgroup, but the last dose was different. Conclusions The present study confirms the low antigenicity of incoBoNT/A, which has immediate consequences for patient management, and the use of higher doses and shorter durations of reinjection intervals in botulinum toxin therapy.

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Section: Introductionmentioning

confidence: 99%

Effective long-term treatment with incobotulinumtoxin (Xeomin®) without neutralizing antibody induction: a monocentric, cross-sectional study

et al. 2020

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“…18 Although they are constituted by parasympathetic and sympathetic elements, a recent clinical trial has demonstrated the reduction of long-term atrial tachyarrhythmias in paroxysmal AF patients who underwent cardiac surgery, by specific parasympathetic denervation with botulinum toxin injection on EAT. [19][20][21] However, the unsuccessful results achieved in some patients, as well as the association between EAT and AF recurrence after catheter ablation, 22 suggest a possible interaction between parasympathetic activity and epicardial fat in arrhythmogenesis perpetuation. One of the most important parasympathetic neurotransmitters is acetylcholine (ACh), which can regulate the endocrine/paracrine activity of epicardial fat.…”

Section: Introductionmentioning

confidence: 99%

Inflammatory and lipid regulation by cholinergic activity in epicardial stromal cells from patients who underwent open‐heart surgery

Couselo‐Seijas

Lopez-Canoa

Fernández

et al. 2020

J Cellular Molecular Medi

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The modulation of acetylcholine (ACh) release by botulinum toxin injection into epicardial fat diminishes atrial fibrillation (AF) recurrence. These results suggest an interaction between autonomic imbalance and epicardial fat as risk factors of AF. Our aim was to study the inflammatory, lipidic and fibroblastic profile of epicardial stroma from patients who underwent open‐heart surgery, their regulation by cholinergic activity and its association with AF. We performed in vitro and ex vivo assays from paired subcutaneous and epicardial stromal cells or explants from 33 patients. Acute ACh effects in inflammation and lipid‐related genes were analysed by qPCR, in intracellular calcium mobilization were performed by Fluo‐4 AM staining and in neutrophil migration by trans‐well assays. Chronic ACh effects on lipid accumulation were visualized by AdipoRed. Plasma protein regulation by parasympathetic denervation was studied in vagotomized rats. Our results showed a higher pro‐inflammatory profile in epicardial regarding subcutaneous stromal cells. Acute ACh treatment up‐regulated monocyte chemoattractant protein 1 levels. Chronic ACh treatment improved lipid accumulation within epicardial stromal cells (60.50% [22.82‐85.13] vs 13.85% [6.17‐23.16], P < .001). Additionally, patients with AF had higher levels of fatty acid‐binding protein 4 (1.54 ± 0.01 vs 1.47 ± 0.01, P = .005). Its plasma levels were pronouncedly declined in vagotomized rats (2.02 ± 0.21 ng/mL vs 0.65 ± 0.23 ng/mL, P < .001). Our findings support the characterization of acute or chronic cholinergic activity on epicardial stroma and its association with AF.

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“…The effects of the Botulism toxin can last anywhere between one and six months and provide a better, untaxing alternative to the use of β-blocker medication. In studies by Pokushalov et al and Romanov et al the number of AF recurrences in patients administered Botulism injections showed a decrease of AF instances (7% Botulism group, 30% Placebo group, and 23.3% Botulism group, 50% Placebo group) at 12 and 36 months, respectively [ 127 , 128 ]. The Botulism toxin was found to induce a pronounced alteration of heart rate variability (HRV) in patients at six months, with heart rate parameters remaining significantly reduced during follow-up [ 127 ].…”

Section: Gp Ablation For Afmentioning

confidence: 99%

Ganglionated Plexi Ablation for the Treatment of Atrial Fibrillation

Avazzadeh

McBride

O’Brien³

et al. 2020

JCM

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Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and is associated with significant morbidity and mortality. The autonomic nervous system (ANS) plays an important role in the initiation and development of AF, causing alterations in atrial structure and electrophysiological defects. The intrinsic ANS of the heart consists of multiple ganglionated plexi (GP), commonly nestled in epicardial fat pads. These GPs contain both parasympathetic and sympathetic afferent and efferent neuronal circuits that control the electrophysiological properties of the myocardium. Pulmonary vein isolation and other cardiac catheter ablation targets including GP ablation can disrupt the fibers connecting GPs or directly damage the GPs, mediating the benefits of the ablation procedure. Ablation of GPs has been evaluated over the past decade as an adjunctive procedure for the treatment of patients suffering from AF. The success rate of GP ablation is strongly associated with specific ablation sites, surgical techniques, localization techniques, method of access and the incorporation of additional interventions. In this review, we present the current data on the clinical utility of GP ablation and its significance in AF elimination and the restoration of normal sinus rhythm in humans.

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Long-term suppression of atrial fibrillation by botulinum toxin injection into epicardial fat pads in patients undergoing cardiac surgery: Three-year follow-up of a randomized study

Cited by 88 publications

References 20 publications

Effective long-term treatment with incobotulinumtoxin (Xeomin®) without neutralizing antibody induction: a monocentric, cross-sectional study

Effective long-term treatment with incobotulinumtoxin (Xeomin®) without neutralizing antibody induction: a monocentric, cross-sectional study

Inflammatory and lipid regulation by cholinergic activity in epicardial stromal cells from patients who underwent open‐heart surgery

Ganglionated Plexi Ablation for the Treatment of Atrial Fibrillation

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