Objective. Prior animal studies suggest that botulinum toxin injection into the epicardial fat pads can suppress atrial fibrillation (AF) inducibility. The purpose of the present study was to assess the efficacy and safety of endocardial botulinum toxin injection into epicardial fat pads and intramyocardial left atrial ganglionated plexi (GP) for preventing AF. Methods. Twenty-four dogs were separated into 3 groups: endocardial approach for botulinum toxin (Xeomin, Germany) injection into epicardial fat pads and intramyocardial GPs; endocardial approach for placebo injection (0.9% normal saline; control 1; n = 8) and epicardial approach for botulinum toxin injection (control 2; n = 8). Results. A mean of 6.9±1.7 intramyocardial injections (10 U/0.2 mL at each) and 3 injections (50 U/1 mL at each) were administered into each site exhibiting a positive vagal response and into each epicardial fat pad in all groups (p>0.05 between groups). The injections of botulinum toxin demonstrated dramatic prolongation of ERP in all PV-atrial junctions. This effect correlated with less pronounced ERP shortening in response to vagal nerve stimulation. Suppression of AF inducibility was observed at 7 days after endocardial botulinum toxin injections. The level of AF inducibility was: at 7 days – 57% (p 0.05 for all). The effect of AF suppression disappeared at 3 months. No procedure-related complications occurred. Conclusion. Botulinum toxin injection into intramyocardial GPs and epicardial fat pads by an endocardial approach is feasible and safe. It provides complete removal of cardiac vagal responses and reliably reduces vulnerability to atrial fibrillation.

Objective. This randomized clinical trial was designed to assess the impact of pulmonary vein isolation (PVI) combined with LAA occlusion on patients with high-risk AF. Methods. Patients with a history of symptomatic paroxysmal (P) AF and/or persistent (Pers) AF and CHA2DS2-VASc score ≥2 and HAS-BLED score ≥3 were randomized in groups with PVI only (n = 44) and PVI combined with LAA occlusion (n = 45). All patients were followed during 24 months in order to evaluate the safety of thromboembolic complications and to monitor the heart rhythm conducted by means of an implantable cardiac monitor. Results. 6 patients from the PVI with LAA occlusion group were transferred to the PVI only group because of a failure to implant a LAA closure device. Based on ILR data, by the end of the follow-up 33 (66%) out of 50 patients in the PVI only group and 23 (59%) out of 39 patients in the PVI with LAA closure device implantation group were free from atrial fibrillation and flutter without antiarrhythmic drugs (p = 0.34). In the blanking period, AF% was significantly higher in the PVI with LAA closure group than that in the PVI-only group, 9.7±10.8 and 4.2±4.1% respectively (p = 0.004). After the blanking period, the AF% was similar in both groups. During the entire follow-up, no AF/intervention-related complications were observed. Conclusion. The combination of LAA closure device implantation with PVI seems to be a safe procedure. However, it does not improve the efficacy of PVI in patients with symptomatic refractory AF. But in the blanking period LAA occlusion increases AF %.

Objective. Prior animal studies suggest that botulinum toxin injection into the epicardial fat pads can suppress atrial fibrillation (AF) inducibility. The purpose of the present study was to assess the efficacy and safety of endocardial botulinum toxin injection into epicardial fat pads and intramyocardial left atrial ganglionated plexi (GP) for preventing AF.Methods. Twenty-four dogs were separated into 3 groups: endocardial approach for botulinum toxin (Xeomin, Germany) injection into epicardial fat pads and intramyocardial GPs; endocardial approach for placebo injection (0.9% normal saline; control 1; n = 8) and epicardial approach for botulinum toxin injection (control 2; n = 8).Results. A mean of 6.9±1.7 intramyocardial injections (10 U/0.2 mL at each) and 3 injections (50 U/1 mL at each) were administered into each site exhibiting a positive vagal response and into each epicardial fat pad in all groups (p>0.05 between groups).The injections of botulinum toxin demonstrated dramatic prolongation of ERP in all PV-atrial junctions. This effect correlated with less pronounced ERP shortening in response to vagal nerve stimulation. Suppression of AF inducibility was observed at 7 days after endocardial botulinum toxin injections. The level of AF inducibility was: at 7 days – 57% (p<0.001 vs placebo; p<0.001 vs baseline); at 14 days – 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 months – 23% (p = 0.003; p = 0.06 vs baseline). There were no differences between botulinum groups (p>0.05 for all). The effect of AF suppression disappeared at 3 months. No procedure-related complications occurred.Conclusion. Botulinum toxin injection into intramyocardial GPs and epicardial fat pads by an endocardial approach is feasible and safe. It provides complete removal of cardiac vagal responses and reliably reduces vulnerability to atrial fibrillation.

Objective. The key element of the onset and progression of atrial fibrillation is an autonomic nervous system. The aim of this study was to assess the electrophysiological efficacy and periprocedural safety of Type A botulinum toxin, the preparation that safely blocks the conduction without any serious complications. Methods. 30 mini pigs (weight 15-20 kg), were randomized into two groups. The first group (n = 15) received botulinum toxin injected in the projection of ANS ganglion plexus of the left atrium, while 0.9% sodium chloride solution was administered in the same zones of animals of the second (control) group (n = 15). Electrophysiological examination of the left atrium and procedure safety was carried out at baseline and 7, 14, 21, 30 days of follow-up.Results. 24 (80%) out of 30 animals survived. All exclusions were not related with the injection procedure. No significant complications, vital functional disorders, a decrease in left ventricular ejection fraction or a high level of cardiac toxic markers were observed in both groups. Starting from 7 to 30 days after the procedure we observed the statistically significant difference between the left atrium effective refractory period of the botulinum toxin and control group (12.4±3.5% versus 31.2±5.6%, p<0.001, respectively) on the 30th day. Also noticeable was AF inducibility reduction only in the botulinum toxin group: at baseline 71±107%; on the 30th day 41±11.4% (p<0.001).Conclusion. The epicardial botulinum toxin injection into the main projections of the left atrium autonomic nervous system is an effective and safe method reducing vulnerability of the myocardium to AF.

Цель. Оценить влияние изоляции легочных вен в сочетании с окклюзией ушка левого предсердия у пациентов с высоким риском развития тромбоэмболических осложнений при фибрилляции предсердий. Методы и результаты. Пациентов с симптоматичной пароксизмальной или персистирующей формой фибрилляции предсердий, рефрактерной не менее чем к двум антиаритмическим препаратам, с риском возникновения тромбоэмболических осложнений по шкале CHA2DS2-VASc не менее 2 баллов и риском возникновения кровотечений по шкале HAS-BLED не менее 3 баллов рандомизировали в группы только изоляции легочных вен (n = 44) и изоляции легочных вен в сочетании с окклюзией ушка левого предсердия (n = 45). Всех пациентов наблюдали в течение 24 мес. для оценки безопасности тромбоэмболических осложнений и контроля сердечного ритма, который проводили с помощью имплантируемого аппарата длительного мониторирования электрокардиограммы. Шесть пациентов из группы изоляции легочных вен в сочетании с окклюзией ушка левого предсердия переведены в группу изоляции легочных вен ввиду невозможности имплантации окклюдера ушка левого предсердия. C учетом кроссоверов к концу наблюдения у 33 (66%) из 50 пациентов в группе изоляции легочных вен и у 23 (59%) из 39 пациентов в группе изоляции легочных вен в сочетании с имплантацией окклюдера ушка левого предсердия не было фибрилляции и трепетания предсердий без применения антиаритмических препаратов (р = 0,34). Процент фибрилляции предсердий в «слепом» периоде был достоверно выше в группе изоляции легочных вен с окклюзией ушка левого предсердия по сравнению с группой изоляции легочных вен 9,7±10,8 против 4,2±4,1% (p = 0,004). После «слепого» периода процент фибрилляции предсердий был одинаковым в обеих группах. В течение всего наблюдения не отмечены осложнения, связанные с фибрилляцией предсердий или вмешательством (инсульт, тромбоэмболия). Выводы. Изоляция легочных вен в сочетании с имплантацией окклюдера ушка левого предсердия является безопасным методом, но не повышает эффективность изоляции легочных вен у пациентов с симптоматической фибрилляцией предсердий. Однако окклюзия ушка левого предсердия в «слепом» периоде увеличивает процент фибрилляции предсердий.