29-06: Inducibility of Atrial Fibrillation After Epicardial Injection of the new pharmaceutical composition containing botulinum toxin into epicardial fat pads

Abstract

Introduction: Prior clinical and animal studies suggest that botulinum toxin injection into the epicardial fat pads can suppress AF recurrences and inducibility. However, currently known botulinum toxin compositions do not have a prolonged action, nor increase the therapeutic effect of botulinum toxin and are not intended to treat cardiac arrhythmias. The aim of the present study was to assess the efficacy and safety of the new pharmaceutical composition containing botulinum toxin and mucopolysaccharide injection into epicardial fat pads for prevention of AF. Methods: 24 dogs were separated into 3 groups: epicardial approach for the new pharmaceutical composition containing botulinum toxin and mucopolysaccharide (chitosan; WO2014184746 A1) injection into 3 main epicardial fat pads, epicardial approach for placebo (normal saline) injection (control 1; n=8) and epicardial approach for pure botulinum toxin injection (control 2; n=8). Results: 3 epicardial injections (50 unit of botulinum toxin per 1 mL at each) were administrated into 3 main left atrial autonomic nervous system projection of each animal. Injections of all forms botulinum toxin demonstrated dramatic prolongation of ERP in all PV-atrial junctions and vagal stimulation shortened ERP was less pronounced. Suppression of AF inducibility was observed at day 7 after all forms botulinum toxin group injections. The reduction of AF inducibility after pure botulinum toxin injection was: at 7 day-57% (p<0.001 vs placebo; p<0.001 vs baseline); at 14day - 61% (p<0.001 vs placebo; p<0.001 vs baseline); at 1 month - 38% (p<0.001 vs placebo; p<0.001 vs baseline); at 3 month-23% (p=0.003; p=0.06 vs baseline). Composition containing botulinum toxin and mucopolysaccharide showed the lowest AF inducibility and prolonged effect: at 7 day-86% (p<0.05 vs pure form); at 14 day-75% (p<0.05 vs pure form); at 1 month-71% (p<0.05 vs pure form); at 3 month-65% (p<0.05 vs pure form). No cardiac suppressive effect or significant procedure-related complications occurred. Conclusions: Composition containing botulinum toxin and mucopolysaccharide injection into epicardial fat pads was feasible and safe, increased and prolonged effect of complete abolition of cardiac vagal responses and significant AF suppression.