Neuromodulation for Ventricular Tachycardia and Atrial Fibrillation: A Clinical Scenario-Based Review.

Autonomic dysregulation in cardiovascular disease plays a major role in the pathogenesis of arrhythmias. Cardiac neural control relies on complex feedback loops consisting of efferent and afferent limbs, which carry sympathetic and parasympathetic signals from the brain to the heart and sensory signals from the heart to the brain. Cardiac disease leads to neural remodeling and sympathovagal imbalances with arrhythmogenic effects. Preclinical studies of modulation at central and peripheral levels of the cardiac autonomic nervous system have yielded promising results, leading to early stage clinical studies of these techniques in atrial fibrillation and refractory ventricular arrhythmias, particularly in patients with inherited primary arrhythmia syndromes and structural heart disease. However, significant knowledge gaps in basic cardiac neurophysiology limit the success of these neuromodulatory therapies. This review discusses the recent advances in neuromodulation for cardiac arrhythmia management, with a clinical scenario-based approach aimed at bringing neurocardiology closer to the realm of the clinical electrophysiologist.

Effect of Lidocaine Injection of Ganglionated Plexi in a Canine Model and Patients With Persistent and Long-Standing Persistent Atrial Fibrillation.

Background This study assessed the effect of blockading neural transmission in the ganglionated plexi by injecting lidocaine into fat pads in the vagal nerve stimulation canine model and patients with persistent atrial fibrillation ( AF ). Methods and Results An efficacy test of lidocaine injection was performed in 7 canines. During vagal nerve stimulation, AF was sustained for >5 minutes. The lidocaine was injected into ganglionated plexi during sinus rhythm and reinduction of AF was attempted. Six patients with persistent AF were studied at open heart surgery. Lidocaine was injected into ganglionated plexi. Atrial electrograms were recorded from 96 epicardial electrodes covering Bachmann's bundle and atrial appendages. In the canine vagal nerve stimulation AF model, AF was not inducible in 4 of 7 after lidocaine injection. In patients with persistent AF , during baseline AF , there was a left atrium ( LA )-to-right atrium ( RA ) frequency gradient ( LA , mean cycle length [ CL ] 175±17 ms; RA , mean CL 192±17 ms; P<0.01). After lidocaine injection, AF persisted in all patients, and the LA -to- RA frequency gradient disappeared ( LA , mean CL 186±13 ms; RA , mean CL 199±23 ms; P=0.08). Comparison of mean CL s before and after lidocaine demonstrated prolongation of LA CL s ( P<0.05) with no effect on RA CL s. Conclusions In the canine vagal nerve stimulation AF model, lidocaine injection decreased inducibility of AF . In patients with persistent AF , atrial electrograms from the LA had shorter CL s than RA , indicating an LA -to- RA frequency gradient. Lidocaine injection significantly prolonged only LA CL s, explaining disappearance of the LA -to- RA frequency gradient. The mechanism of localized atrial electrogram CL prolongation in patients with persistent AF is uncertain.

Electroanatomic-mapping-guided cardioneuroablation versus combined approach for vasovagal syncope: a cross-sectional observational study.

PURPOSE: This study was designed to assess the efficacy of electroanatomic-mapping (EAM)-guided cardioneuroablation (CNA) vs combined approach for vasovagal syncope (VVS). METHODS: Twenty patients with VVS refractory to conventional treatments who underwent CNA in our institution were enrolled in the study. Twelve of these patients underwent recently introduced EAM-guided CNA using signal-based approach while 8 patients underwent combined CNA using a combination of high-frequency stimulation and spectral analysis. Both atria and coronary sinus were divided into seven segments to categorize distribution of ganglionated plexi in ablation sites. Clinical responses were evaluated and compared in terms of prodromal symptoms and syncope recurrence rates. Electrophysiological parameters and heart rate variability (HRV) analysis were used to evaluate procedural response. RESULTS: Procedural endpoints were achieved in all cases without any serious adverse events. Compared with the combined approach group, EAM-guided CNA was related to a shorter procedure and fluoroscopy times (p < 0.001). The mean number of ablation points in each anatomical segment was comparable between groups. The prodromal symptoms demonstrated a significant and comparable decrease after CNA. Median event-free survival was comparable between groups (χ2 = 0.03, p = 0.87). There was no new syncopal episode in any case at the end of 6-month follow-up. In the combined approach group, new syncope episodes occurred in two cases after 12-month follow-up. HRV parameters indicating parasympathetic activity were comparably decreased after ablation in both groups. CONCLUSION: This pilot study shows that EAM-guided CNA strategy is feasible and safe in VVS patients resistant to conventional therapies.

Integrity of the Ganglionated Plexi Is Essential to Parasympathetic Innervation of the Atrioventricular Node by the Right Vagus Nerve.

INTRODUCTION: Radiofrequency isolation of pulmonary vein can be accompanied by transient sinus bradycardia or atrioventricular nodal (AVN) block, suggesting an influence on vagal cardiac innervation. However, the importance of the atrial fat pads in relation with the vagal innervation of AVN in humans remains largely unknown. The aim of this study was to evaluate the role of ganglionated plexi (GP) in the innervation of the AVN by the right vagus nerve. METHODS AND RESULTS: Direct epicardial high-frequency stimulation (HFS) of the GP (20 patients) and the right vagus nerve (10 patients) was performed before and after fat pad exclusion or destruction in 20 patients undergoing thoracoscopic epicardial ablation for the treatment of persistent AF. Asystole longer than 3 seconds or acute R-R prolongation over 25% was considered as a positive response to HFS. Prior to the ablation, positive responses to HFS were detected in 3 GPs in 7 patients (35%), 2 GPs in 5 patients (25%), and one GP in 8 patients (40%). After exclusion of the fat pads, all patients had a negative response to HFS. All the patients who exhibited a positive response to right vagus nerve stimulation (n = 10) demonstrated negative responses after the ablation. CONCLUSION: The integrity of the GP is essential for the right vagus nerve to exert physiological effects of on AVN in humans.

Low-intensity atrial ganglionated plexi stimulation decreases the serum level of inflammatory factors in canine.

BACKGROUND: Activation of efferent vagus fibers exerts an anti-inflammatory role, a mechanism known as the cholinergic anti-inflammatory pathway. We hypothesised that stimulation of atrial ganglionated plexi (GP) may also be anti-inflammatory. METHODS: Six-hour low-intensity GP stimulation was performed in eight dogs and the serum levels of acetylcholine (Ach), C reactive protein (CRP), interleukin-6 (IL-6), high-mobility group box 1 (HMGB1) were determined with enzyme-linked immunosorbent assay kits. RESULTS: The serum level of acetylcholine was significantly increased (P<0.05) while the serum levels of inflammatory factors of C reactive protein, interleukin-6 and high-mobility group box 1 were markedly decreased after six-hour GP stimulation (all P<0.05). CONCLUSIONS: These results suggest that GP stimulation exerts an anti-inflammatory role and might be a therapeutic option for inflammatory heart diseases.

Autonomic denervation added to pulmonary vein isolation for paroxysmal atrial fibrillation: a randomized clinical trial.

OBJECTIVES: The aim of this study was to investigate whether the combination of conventional pulmonary vein isolation (PVI) by circumferential antral ablation with ganglionated plexi (GP) modification in a single ablation procedure, yields higher success rates than PVI or GP ablation alone, in patients with paroxysmal atrial fibrillation (PAF). BACKGROUND: Conventional PVI transects the major left atrial GP, and it is possible that autonomic denervation by inadvertent GP ablation plays a central role in the efficacy of PVI. METHODS: A total of 242 patients with symptomatic PAF were recruited and randomized as follows: 1) circumferential PVI (n = 78); 2) anatomic ablation of the main left atrial GP (n = 82); or 3) circumferential PVI followed by anatomic ablation of the main left atrial GP (n = 82). The primary endpoint was freedom from atrial fibrillation (AF) or other sustained atrial tachycardia (AT), verified by monthly visits, ambulatory electrocardiographic monitoring, and implantable loop recorders, during a 2-year follow-up period. RESULTS: Freedom from AF or AT was achieved in 44 (56%), 39 (48%), and 61 (74%) patients in the PVI, GP, and PVI+GP groups, respectively (p = 0.004 by log-rank test). PVI+GP ablation strategy compared with PVI alone yielded a hazard ratio of 0.53 (95% confidence interval: 0.31 to 0.91; p = 0.022) for recurrence of AF or AT. Fluoroscopy duration was 16 ± 3 min, 20 ± 5 min, and 23 ± 5 min for PVI, GP, and PVI+GP groups, respectively (p < 0.001). Post-ablation atrial flutter did not differ between groups: 5.1% in PVI, 4.9% in GP, and 6.1% in PVI+GP. No serious adverse procedure-related events were encountered. CONCLUSIONS: Addition of GP ablation to PVI confers a significantly higher success rate compared with either PVI or GP alone in patients with PAF.