Epicardial Fat Pads Research Articles

Quantitative investigation of acute lesions created by ethanol infusion into the vein of Marshall

BackgroundEthanol infusion into the vein of Marshall (EIVOM) has been performed as an adjunctive atrial fibrillation therapy. However, the time course change, quantitative lesion investigation, and effects on epicardial fat pads and fractionated atrial electrograms created by EIVOM have never been investigated. ObjectiveThis study aimed to perform a quantitative analysis of lesions created by EIVOM. MethodsWe created voltage maps using a 3-dimensional mapping system immediately before and 30 minutes and 60 minutes after performing EIVOM to study the time course change in the lesions. We compared differences in the average contact force value required for successful conduction block in the Marshall vein area of patients with and without EIVOM. We also investigated effects of EIVOM on the area of complex fractionated atrial electrograms before and after EIVOM. We measured the total epicardial fat pad volume before and after EIVOM by computed tomography. ResultsVoltage was significantly reduced after EIVOM, and there were significant differences in voltage reduction between the control status and 30 minutes and 60 minutes after EIVOM (P < .05). The average contact force value was significantly lower with vs without EIVOM (P < .05). The total epicardial fat volume and complex fractionated atrial electrogram area also significantly decreased after EIVOM (P < .05). ConclusionEIVOM provided significant therapeutic effects on the left atrial tissue perpetuating atrial fibrillation, which was demonstrated by a quantitative analysis.

Localization of ganglionated plexi by high density mapping: an atropine-response analysis

Abstract Introduction Growing interest has emerged around cardiac autonomic nervous system driven by ablation approaches for the treatment of neurally-mediated syncope (NMS). Ganglionated-plexi (GPs) located in the epicardial fat pads are the main target of ablative therapies, but little is known about the finest method to track their location from the endocardium. Most current techniques rely on empirical research of signal fragmentation and/or vagal response at anatomical landmarks. A poor accuracy in targeting GPs may lead to the risk of incomplete or over-extensive ablation. Purpose We analyzed the atrial electrograms (EGMs) in healty subjects and their response to atropine to describe physiological fragmentation and the relationship with vagal output. Methods Study partecipants were selected from young patients without structural heart desease who underwent electrophysiological study (EPS) for standard indications. High-density mapping of right atrium was performed before and after administration of 2 mg atropine at the end of the planned procedure. Offline analyses were performed comparing the two maps of each patient focusing on the fragmentation of the atrial EGMs. Results The study cohort comprised 10 patients (mean age of 39±11 years, 6 males). The indication for EPS was: supraventricular tachycardia (SVT) ablation in 9 patients, syncope in 1 patient. High density three-dimensional electro-anatomic maps (EAM) were all obtained with a multipolar catheter during sinus rhythm (number of points: 8794±937 in basal maps and 9007±1296 after atropine, p=0,87). The response to atropine was documented by an increase in heart rate (mean increase 59 ± 19% of basal cycle length). All basal maps showed a similar pattern of fragmentation in the posterior-septal wall reflecting the anatomical distribution of right GPs. In particular, three main stations were identified in the supero-, mid- and infero-posterior regions. Fragmentation of EGMs was found to progress from the edge to the core of each area. After administration of atropine, a reduction in fractionated area was observed in all patients. Filtering the maps according to a cut-off of fragmentation ≥ 6 peaks allowed identification of the nucleus with the highest degree of variation after atropine injection (mean basal area = 0,89 ± 0,81 cm2 ; mean atropine area = 0,44 ± 0,56 cm2 p&amp;lt;0,001). Conclusion Fragmentation of atrial electrograms is a dynamic property related to vagal output. High density mapping with a high pass filter of 6 peaks allows to identify the smallest vagal sensitive area in the anatomical stations of the GPs.

Efficacy and Safety of Botulinum Toxin Type A for the Prevention of Postoperative Atrial Fibrillation

BackgroundPostoperative atrial fibrillation (POAF) is associated with increased morbidity and mortality. Epicardial injection of botulinum toxin may suppress POAF. ObjectivesThis study sought to assess the safety and efficacy of AGN-151607 for the prevention of POAF after cardiac surgery. MethodsThis phase 2, randomized, placebo-controlled trial assessed the safety and efficacy of AGN-151607, 125 U and 250 U vs placebo (1:1:1), for the prevention of POAF after cardiac surgery. Randomization was stratified by age (<65, ≥65 years) and type of surgery (nonvalvular/valve surgery). The primary endpoint was the occurrence of continuous AF ≥30 seconds. ResultsAmong 312 modified intention-to-treat participants (placebo, n = 102; 125 U, n = 104; and 250 U, n = 106), the mean age was 66.9 ± 6.8 years; 17% were female; and 64% had coronary artery bypass graft (CABG) only, 12% had CABG + valve, and 24% had valve surgery. The primary endpoint occurred in 46.1% of the placebo group, 36.5% of the 125-U group (relative risk [RR] vs placebo: 0.80; 95% CI: 0.58-1.10; P = 0.16), and 47.2% of the 250-U group (RR vs placebo: 1.04; 95% CI: 0.79-1.37; P = 0.78). The primary endpoint was reduced in the 125-U group in those ≥65 years of age (RR: 0.64; 95% CI: 0.43-0.94; P = 0.02) with a greater reduction in CABG-only participants ≥65 years of age (RR: 0.49; 95% CI: 0.27-0.87; P = 0.01). Rehospitalization and rates of adverse events were similar across the 3 groups. ConclusionsThere were no significant differences in the rate of POAF with either dose compared with placebo; however, there was a lower rate of POAF in participants ≥65 years undergoing CABG only and receiving 125 U of AGN-151607. These hypothesis-generating findings require investigation in a larger, adequately powered randomized clinical trial. (Botulinum Toxin Type A [AGN-151607] for the Prevention of Post-operative Atrial Fibrillation in Adult Participants Undergoing Open-chest Cardiac Surgery [NOVA]; NCT03779841); A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose Ranging Study to Evaluate the Efficacy and Safety of Botulinum Toxin Type A [AGN 151607] Injections into the Epicardial Fat Pads to Prevent Post-Operative Atrial Fibrillation in Patients Undergoing Open-Chest Cardiac Surgery; 2017-004399-68)

The Intrinsic Cardiac Nervous System: From Pathophysiology to Therapeutic Implications.

The cardiac autonomic nervous system (CANS) plays a pivotal role in cardiac homeostasis as well as in cardiac pathology. The first level of cardiac autonomic control, the intrinsic cardiac nervous system (ICNS), is located within the epicardial fat pads and is physically organized in ganglionated plexi (GPs). The ICNS system does not only contain parasympathetic cardiac efferent neurons, as long believed, but also afferent neurons and local circuit neurons. Thanks to its high degree of connectivity, combined with neuronal plasticity and memory capacity, the ICNS allows for a beat-to-beat control of all cardiac functions and responses as well as integration with extracardiac and higher centers for longer-term cardiovascular reflexes. The present review provides a detailed overview of the current knowledge of the bidirectional connection between the ICNS and the most studied cardiac pathologies/conditions (myocardial infarction, heart failure, arrhythmias and heart transplant) and the potential therapeutic implications. Indeed, GP modulation with efferent activity inhibition, differently achieved, has been studied for atrial fibrillation and functional bradyarrhythmias, while GP modulation with efferent activity stimulation has been evaluated for myocardial infarction, heart failure and ventricular arrhythmias. Electrical therapy has the unique potential to allow for both kinds of ICNS modulation while preserving the anatomical integrity of the system.

Abstract 12958: Temporal Association of Systemic Inflammatory Biomarkers With Incidence of Postoperative Atrial Fibrillation After Botulinum Toxin Type A Administration in Epicardial Fat Pads

Background: A one-time injection of botulinum toxin type A (BoNT/A) in epicardial fat pads was evaluated for post-operative atrial fibrillation (POAF) in patients undergoing open-chest cardiac surgery in the Ph2 NOVA trial. Treatment with 125U BoNT/A numerically reduced the incidence of POAF in the mITT (36.5% vs 46.1%) and CABG populations (28.4% vs 40.0%), with statistical significance observed in the CABG + ≥65 years subgroup (27.5% vs 56.4%; P &lt;0.01). No significant reduction was observed in the 250U group vs placebo. Purpose: Explore systemic inflammatory biomarker changes after treatment with BoNT/A and the temporal relation to incidence of POAF. Methods: This analysis included 308 patients who received 125U BoNT/A (n=103), 250U BoNT/A (n=103), or placebo (n=102). Subgroup analysis was done for CABG (n=198), age ≥65 years (n=185), and CABG + ≥65 years (n=118). Serum samples were collected preoperatively prior to dosing on Day 1, then post-treatment on Days 2-4 to test for IL-6, IL-10, and hsCRP. A 2-sample t test was used for mean concentrations and a linear mixed model was used for fold change (FC) from baseline. Results: Baseline levels of IL-6, IL-10, and hsCRP were similar between treatment groups. Reduction of IL-6 (45.7 ± 4.4 vs 62.4 ± 5.8 pg/mL, P &lt;0.05; 10.8 vs 15.9 FC, P &lt;0.01) and IL-10 (1.49 ± 0.13 vs 2.04 ± 0.24 pg/mL, P &lt;0.05; 1.96 vs 2.66 FC, P &lt;0.01) was most significant on Day 2 in CABG patients treated with 125U vs placebo, which aligns with the highest rate and risk of POAF (Figure 1). Mean hsCRP was most significantly reduced on Day 4 in the 250U group among CABG patients (193 ± 8 vs 227 ± 10 mg/dL, P &lt;0.01) followed by 125U vs placebo (196 ± 10 vs 227 ± 10 mg/dL, P &lt;0.05); a similar dose-dependent reduction was observed by FC analysis. Conclusions: Treatment with 125U BoNT/A in cardiac surgery patients lowered the incidence of POAF vs placebo and reduced postoperative systemic IL-6 and IL-10 on Day 2, most significantly in the CABG population.

Abstract 11520: Safety and Efficacy of Botulinum Toxin Type A for Prevention of Postoperative Atrial Fibrillation in Cardiac Surgery Patients: Pulmonary Function Test Results From the Phase 2 NOVA Study

Background: Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery. Autonomic neuromodulation, including injection of botulinum toxin into epicardial fat pads, may suppress and/or attenuate atrial fibrillation. The respiratory safety of a potential preventative treatment for AF is critical. Aim: To assess efficacy and pulmonary safety of botulinum toxin type A (BoNT/A; AGN-151607) 125U and 250U vs placebo for prevention of POAF after coronary artery bypass graft and/or valve surgery. Methods: NeurOtoxin for the PreVention of post-operative Atrial fibrillation (NOVA; NCT03779841) was a phase 2, international, multicenter, randomized, placebo-controlled trial. The primary endpoint was proportion of patients with continuous AF ≥30 seconds within the first 30 days. Respiratory function was assessed via pulmonary function tests (PFTs) performed at baseline and day 30 after treatment. Adverse events (AEs), serious adverse events (SAEs), and time to extubation were recorded. Results: A total of 323 patients were randomized: BoNT/A 125U (n=106), 250U (n=109), placebo (n=108). The primary endpoint occurred in 46.1% of the placebo group, 36.5% of the 125U group (relative risk [RR] vs placebo, 0.80 [95% CI: 0.58, 1.10]; P =0.16), and 47.2% of the 250U group (RR vs placebo, 1.04 [95% CI: 0.79, 1.37]; P =0.78). Baseline, day 30, and change from baseline PFT results were similar for active treatment vs placebo ( Table ). Median time to extubation was 9.7, 9.6, and 9.6 h in the placebo, 125U, and 250U groups, respectively. Respiratory AEs were reported in 42.9%, 38.1%, and 50.5% of patients, and respiratory SAEs in 11.4%, 6.7%, and 5.5% of patients in the placebo, 125U, and 250U groups, respectively. Conclusion: In this analysis of respiratory function, there appeared to be no detrimental effect of AGN-151607 compared with placebo, as evidenced by similar outcomes in PFT parameters and respiratory AE/SAE incidences among treatment arms.

CE-521-04 VASOVAGAL SYNCOPE WITH ISOLATED ATRIOVENTRICULAR BLOCK FOLLOWING CARDIONEURAL ABLATION DEMONSTRATING DISTINCT INNERVATION OF THE SINUS AND ATRIOVENTRICULAR NODES

Radiofrequency ablation (RFA) of cardiac parasympathetic ganglionated plexi (GPs), termed cardioneural ablation (CNA), has been shown to successfully treat vasovagal syncope (VVS). Sinus (SN) and atrioventricular (AVN) nodes are innervated by distinct GPs in the epicardial fat pads of both atria. We present a case of CNA of SN-specific GPs for VVS eliminating sinus arrest, but recurrent syncope with AV block.

Importance of vagal tone before atrial fibrillation onset

Neuromodulation is increasingly attempted during ablation procedures for atrial fibrillation (AF). The role of the cardiac autonomic nervous system (CANS) in triggering paroxysmal AF episodes is well-established. Heart rate variability (HRV) provides information on the final output of the influence of the CANS. The high frequency component (HF: 0.15–0.40 Hz) reflects vagal activity, and the low frequency component (LF: 0.04–0.15 Hz) reflects a complex mix of parasympathetic, sympathetic, and other unidentified non-linear factors. Therefore, clinically, the analysis of the temporality of these parameters could be useful for the selection of additional therapy during AF ablation procedures. Study the significance of CANS variations prior to AF onset by tracking the evolution of frequential parameters of HRV and premature atrial contractions (PACs). We screened our ECG Holter monitoring database of more than 20,000 patients to find those with paroxysmal AF episodes recorded. Three hundred analyzable AF onsets from 210 paroxysmal AF patients were labelled. We analyzed HRV frequential parameters by segments every 300 RR intervals, progressing beat by beat to allow the evolution of the spectral parameters of the HRV and count of PACs to be closely monitored. We focused on the evolution of low (LF) and high frequencies (HF), as well as the LF/HF ratio and the number of PACs. We observed several cyclical variations of increasing amplitude in CANS followed by a final significant upward shift in HF and LF preceding the onset of AF. The number of PACs shows a progressive increase in parallel to autonomic changes (see Fig. 1 ). These data suggest that vagal influence is preponderant in the AF onset for most of the patients. This is in favor of a thoracoscopic approach to neuromodulation procedures, as ganglionic plexi contain mainly parasympathetic neurons and are located in epicardial fat pads.

Design and Rationale of a Phase 2 Study of NeurOtoxin (Botulinum Toxin Type A) for the PreVention of Post-Operative Atrial Fibrillation – The NOVA Study

Post-operative AF (POAF) is the most common complication following cardiac surgery, occurring in 30% to 60% of patients undergoing bypass and/or valve surgery. POAF is associated with longer intensive care unit/hospital stays, increased healthcare utilization, and increased morbidity and mortality. Injection of botulinum toxin type A into the epicardial fat pads resulted in reduction of AF in animal models, and in two clinical studies of cardiac surgery patients, without new safety observations. The objective of NOVA is to assess the use of AGN-151607 (botulinum toxin type A) for prevention of POAF in cardiac surgery patients. This randomized, multi-site, placebo-controlled trial will study one-time injections of AGN-151607 125 U (25 U / fat pad) and 250 U (50 U / fat pad) or placebo during cardiac surgery in ∼330 participants. Primary endpoint: % of patients with continuous AF ≥ 30 s. Secondary endpoints include several measures of AF frequency, duration, and burden. Additional endpoints include clinically important tachycardia during AF, time to AF termination, and healthcare utilization. Primary and secondary efficacy endpoints will be assessed using continuous ECG monitoring for 30 days following surgery. All patients will be followed for up to 1 year for safety. The NOVA Study will test the hypothesis that injections of AGN-151607 will reduce the incidence of POAF and associated resource utilization. If demonstrated to be safe and effective, the availability of a one-time therapy for the prevention of POAF would represent an important treatment option for patients undergoing cardiac surgery.

Why is neuromodulation effect of pulmonary vein isolation not same in all cases?

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac ganglionated plexi (GPs) of the autonomic system are primarily located in major epicardial fat pads adjacent to the left atrium and pulmonary vein junctions. These structures may play a central role in both the initiation and maintenance of atrial fibrillation (AF). Previous studies reported modification of GPs during pulmonary vein isolation (PVI) may increase rate of sinus node and AF-free survival. However, a deficiency certainly existed why is modification of GPs observed in some patients during PVI but not in others? Purpose We aimed to evaluate ratio of ablation points within classical antral circumferential ablation lines for PVI and distribution of 4 major atrial ganglionated plexus. Methods Thirty-eight consecutive patients undergoing ablation of GP for vagally mediated bradyarrhythmias were evaluated. All GP sites were detected by using previously defined fragmented electrogram based strategy which is a validated tool when compared with a combination of spectral analysis and high frequency stimulation to detect GPs. Estimated ablation lines for antral circumferential ablation was defined as a circumferential isolation line performed ≥1 cm away from the pulmonary vein ostium as identified by 3D electroanatomical reconstruction (Figure 1). The total number of ablation points in each GP sites and ratio of ablation points within estimated antral circumferential ablation lines were recorded. Results The great majority of ablation points were detected at the insertion of the right pulmonary veins. Number of ablation points in each GP site in descending order is as follows: (1) the right superior GP = 13.6 ± 6; (2) the left superior GP = 10.5 ± 5; (3) the right inferior GP = 5.9 ± 4; and (4) the left inferior GP = 2.5 ± 3. The ratio of ablation points within estimated antral circumferential ablation lines was higher in right-sided GPs (50.5%±24 for the right superior GP and 30.2%±31 for the right inferior GP vs 18.3%±24 for the left superior GP and 11.6%±26 for the left inferior GP. Figure 2 demonstrates total number of ablation points and the ratio of ablation points within estimated antral circumferential ablation lines in each GP site. Conclusions The present study shows that individual variability of distribution of GPs and how antral ablation was done during PVI might be the main contributors of neuromodulation effect. Further randomized, controlled and multicenter studies should be performed to confirm these findings. Abstract Figure 1

Characterization of the HCN Interaction Partner TRIP8b/PEX5R in the Intracardiac Nervous System of TRIP8b-Deficient and Wild-Type Mice.

The tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b/PEX5R) is an interaction partner and auxiliary subunit of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which are key for rhythm generation in the brain and in the heart. Since TRIP8b is expressed in central neurons but not in cardiomyocytes, the TRIP8b-HCN interaction has been studied intensely in the brain, but is deemed irrelevant in the cardiac conduction system. Still, to date, TRIP8b has not been studied in the intrinsic cardiac nervous system (ICNS), a neuronal network located within epicardial fat pads. In vitro electrophysiological studies revealed that TRIP8b-deficient mouse hearts exhibit increased atrial refractory and atrioventricular nodal refractory periods, compared to hearts of wild-type littermates. Meanwhile, heart rate, sino-nodal recovery time, and ventricular refractory period did not differ between genotypes. Trip8b mRNA was detected in the ICNS by quantitative polymerase chain reaction. RNAscope in situ hybridization confirmed Trip8b localization in neuronal somata and nerve fibers. Additionally, we found a very low amount of mRNAs in the sinus node and atrioventricular node, most likely attributable to the delicate fibers innervating the conduction system. In contrast, TRIP8b protein was not detectable. Our data suggest that TRIP8b in the ICNS may play a role in the modulation of atrial electrophysiology beyond HCN-mediated sino-nodal control of the heart.

The frequency of epicardial fat pads detected by chest x-rays in psoriasis patients

The frequency of epicardial fat pads detected by chest x-rays in psoriasis patients

Ganglionated Plexi Ablation for the Treatment of Atrial Fibrillation.

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.

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

Botulinum toxin (BTX) injections into epicardial fat pads in patients undergoing coronary artery bypass grafting (CABG) has resulted in suppression of atrial fibrillation (AF) during the early postoperative period through 1-year of follow-up in a pilot program. The purpose of this study was to report 3-year AF patterns by the use of implantable cardiac monitors (ICMs). Sixty patients with a history of paroxysmal AF and indications for CABG were randomized 1:1 to either BTX or placebo injections into 4 posterior epicardial fat pads. All patients received an ICM with regular follow-up for 3 years after surgery. The primary end point of the extended follow-up period was incidence of any atrial tachyarrhythmia after 30 days of procedure until 36 months on no antiarrhythmic drugs. The secondary end points included clinical events and AF burden. At the end of 36 months, the incidence of any atrial tachyarrhythmia was 23.3% in the BTX group vs 50% in the placebo group (hazard ratio 0.36; 95% confidence interval 0.14-0.88; P = .02). AF burden at 12, 24, and 36 months was significantly lower in the BTX group than in the placebo group: 0.22% vs 1.88% (P = .003), 1.6% vs 9.5% (P < .001), and 1.3% vs 6.9% (P = .007), respectively. In the BTX group, 2 patients (7%) were hospitalized during follow-up compared with 10 (33%) in the placebo group (P = .02). Injection of BTX into epicardial fat pads in patients undergoing CABG resulted in a sustained and substantial reduction in atrial tachyarrhythmia incidence and burden during 3-year follow-up, accompanied by reduction in hospitalizations.

Temporary autonomic modulation with botulinum toxin type A to reduce atrial fibrillation after cardiac surgery

Postoperative atrial fibrillation (POAF) frequently complicates cardiac surgery and is associated with worse outcomes. The cardiac autonomic nervous system is implicated in the pathogenesis of POAF. The purpose of this study was to determine the efficacy and safety of selective cardiac autonomic modulation in preventing POAF. In this randomized, double-blind, placebo-controlled trial, adults undergoing cardiac surgery were randomized 1:1 to intraoperative injection of 250 units onabotulinumtoxinA (botulinum toxin type A [BoNTA]) or placebo into epicardial fat pads. The study was powered to detect a 40% reduction in relative risk of POAF. Time to first episode of in-hospital POAF was the primary outcome, evaluated in patients receiving injection. Additionally, incidence of POAF, length of stay (LOS), and adverse events were examined. The trial assigned 145 patients to injection, 15 of whom were dropped before treatment, leaving 130 patients for analysis. Overall, 36.5% (23/63) of BoNTA-treated patients developed POAF compared with 47.8% (32/67) of placebo-treated patients. The time-to-event analysis revealed a hazard ratio of 0.69 (95% confidence interval 0.41-1.19; P = .18) for the BoNTA vs placebo arm. There were no significant differences in postoperative hospital LOS (median [interquartile range] 6.0 [3.4] vs 6.2 [3.7] days; P=.51) or adverse events prolonging LOS (27/63 [42.9%] vs 30/67 [44.8%]; P = .83) in patients receiving BoNTA vs placebo. Epicardial injection of onabotulinumtoxinA was without discernible adverse effects, but we failed to detect a significant difference in risk of POAF. Future large-scale studies of epicardial onabotulinumtoxinA injection as a potential POAF prevention strategy should be designed to study smaller, but clinically meaningful, treatment effects.

A novel approach to mapping the atrial ganglionated plexus network by generating a distribution probability atlas.

IntroductionThe ganglionated plexuses (GPs) of the intrinsic cardiac autonomic system are implicated in arrhythmogenesis. GP localization by stimulation of the epicardial fat pads to produce atrioventricular dissociating (AVD) effects is well described. We determined the anatomical distribution of the left atrial GPs that influence atrioventricular (AV) dissociation.Methods and ResultsHigh frequency stimulation was delivered through a Smart‐Touch catheter in the left atrium of patients undergoing atrial fibrillation (AF) ablation. Three dimensional locations of points tested throughout the entire chamber were recorded on the CARTO™ system. Impact on the AV conduction was categorized as ventricular asystole, bradycardia, or no effect. CARTO maps were exported, registered, and transformed onto a reference left atrial geometry using a custom software, enabling data from multiple patients to be overlaid. In 28 patients, 2108 locations were tested and 283 sites (13%) demonstrated (AVD‐GP) effects. There were 10 AVD‐GPs (interquartile range, 11.5) per patient. Eighty percent (226) produced asystole and 20% (57) showed bradycardia. The distribution of the two groups was very similar. Highest probability of AVD‐GPs (>20%) was identified in: inferoseptal portion (41%) and right inferior pulmonary vein base (30%) of the posterior wall, right superior pulmonary vein antrum (31%).ConclusionIt is feasible to map the entire left atrium for AVD‐GPs before AF ablation. Aggregated data from multiple patients, producing a distribution probability atlas of AVD‐GPs, identified three regions with a higher likelihood for finding AVD‐GPs and these matched the histological descriptions. This approach could be used to better characterize the autonomic network.

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

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

Метод эндокардиальной инъекции ботулотоксина в ганглионарные сплетения автономной нервной системы сердца в целях снижения уязвимости к фибрилляции предсердий

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.

Anatomical Consideration in Catheter Ablation of Idiopathic Ventricular Arrhythmias.

Idiopathic ventricular arrhythmias (VAs) are ventricular tachycardias (VTs) or premature ventricular contractions (PVCs) with a mechanism that is not related to myocardial scar. The sites of successful catheter ablation of idiopathic VA origins have been progressively elucidated and include both the endocardium and, less commonly, the epicardium. Idiopathic VAs usually originate from specific anatomical structures such as the ventricular outflow tracts, aortic root, atrioventricular (AV) annuli, papillary muscles, Purkinje network and so on, and exhibit characteristic electrocardiograms based on their anatomical background. Catheter ablation of idiopathic VAs is usually safe and highly successful, but can sometimes be challenging because of the anatomical obstacles such as the coronary arteries, epicardial fat pads, intramural and epicardial origins, AV conduction system and so on. Therefore, understanding the relevant anatomy is important to achieve a safe and successful catheter ablation of idiopathic VAs. This review describes the anatomical consideration in the catheter ablation of idiopathic VAs.

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.

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. 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. 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. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01842529.