Clinical analysis of cardiac autonomic ganglion plexus ablation for bradyarrhythmia: Research protocol for an intervention study.

OBJECTIVE: This study aimed to explore the safety and effectiveness of selective cardiac autonomic ganglion plexus (GP) ablation on patients with bradyarrhythmia. The heart is controlled by its own intrinsic and central autonomic nerves. Increased cardiac vagal tone leads to sinus node dysfunction and atrioventricular conduction disorders, resulting in bradyarrhythmia. Pacemaker implantation can relieve the symptoms of arrhythmia caused by bradycardia, but it is not easy for patients to accept a pacemaker implantation as a form of treatment. Therefore, more and more attention has been paid to cardiac vagus nerve ablation. METHODS: In this study, 20 patients who met the inclusion criteria of GP ablation in the First Affiliated Hospital of Xinjiang Medical University from November 2019 to June 2020 were enrolled. Biochemical and other related examinations along with electrophysiological examinations were conducted before ablation, and then cardiac GP ablation was performed. The patients were followed up 3 times at 3, 6, and 12 months after the operation. RESULTS: The minimum HR and mean HR were significantly increased after treatment with cardiac autonomic GP ablation (p<0.01). Moreover, the SDNN (Standard deviation of Normal-to-Normal Intervals) and RMSSD (Root mean square successive differences between successive R-R intervals) was significantly decreased after treatment with cardiac autonomic ganglion plexus ablation for 6 months and 12 months (p<0.01). CONCLUSION: Cardiac GP ablation is relatively simple and easy to implement in units that have performed radiofrequency ablation for bradyarrhythmias. This procedure can be performed without any new equipment. Some patients with bradycardia may not have a permanent pacemaker implantation and may go in for additional treatment options.

Why is pulmonary vein isolation not enough for vagal denervation in all cases?

Pulmonary vein isolation (PVI) may cause vagal response during radiofrequency application or increase on heart rate after ablation. All those responses are related to inadvertent ablation effect on ganglionated plexi. In the present case, we aimed to explain why vagal response effects of PVI are not same in all cases.

Dissection of Pelvic Autonomic Ganglia and Associated Nerves in Male and Female Rats.

The bilateral major pelvic ganglia (MPG; synonym, pelvic ganglia) are the primary source of postganglionic sympathetic and parasympathetic neurons innervating pelvic organs of rodents; the functionally equivalent structure in humans is the inferior hypogastric plexus. The major pelvic ganglia also provide the route by which lumbar and sacral sensory axons reach the pelvic organs. These complex, mixed ganglia can prove challenging to identify and dissect for further experimental study of normal autonomic mechanisms or to establish preclinical models of disease, injury or visceral pain. Here we describe a protocol to access and visualize these ganglia and their associated nerve tracts. We provide this protocol with schematics for both male and female rats, as the ganglion size and landmarks for identification differ between sexes. The protocol describes removal of the ganglion for in vitro studies, but this method can be integrated into a surgical recovery protocol for experimental interventions (e.g., nerve crush, nerve resection) or for mapping neuronal circuits (e.g., by microinjection of neural tracers). We also demonstrate the primary structures of the ganglion and its associated nerves immediately following dissection and following immunohistochemical staining.

Different effects of additional ganglion plexus ablation on catheter and surgical ablation for atrial fibrillation: a systemic review and meta-analysis.

The effect of ganglion plexus (GP) ablation in addition to pulmonary veins isolation (PVI) for atrial fibrillation (AF) remained controversial between the catheter and surgical-based studies. Eleven studies (five randomized controlled trials and six nonrandomized studies) of 1750 patients were included in a meta-analysis to elucidate the incremental benefit of additional GP ablation in patients undergoing catheter or surgical ablation. Risk ratios were calculated for freedom from AF or AT recurrence after a single procedure. Additional GP ablation was associated with a better rhythm outcome for patients undergone catheter ablation but did not seem to increase freedom from AF/AT for surgical patients. Both paroxysmal and non-paroxysmal AF showed a positive outcome comparing additional GP ablation with PVI alone.

Long-Term Outcome of Additional Superior Vena Cava to Septal Linear Ablation in Catheter Ablation of Atrial Fibrillation.

Background We previously reported the benefit of linear ablation from the superior vena cava to the right atrial septum (SVC-L) within a year after circumferential pulmonary vein isolation (CPVI) in patients with paroxysmal atrial fibrillation (AF). We explored the long-term effects of SVC-L and its potential related mechanisms. Methods and Results Among 2140 consecutive patients with AF ablation, we included 614 patients (73.3% male, aged 57.8±10.7 years, 13.7% with persistent AF) who did not undergo an extra-pulmonary vein left atrial ablation after propensity score matching; of those, 307 had additional SVC-L and 307 had CPVI alone. We evaluated the heart rate variability and computational modeling study to explore mechanisms. Although the procedure time was longer in the SVC-L group than the CPVI group (P<0.001), the complication rates did not differ (P=0.560). During 40.5±24.4 months of follow-up, the rhythm outcome was significantly better in the SVC-L group than the CPVI group (log rank, P<0.001). At 2-year follow-up of heart rate variability, a significantly higher mean heart rate (P=0.018) and a lower ratio of low/high-frequency components (P=0.011) were found with SVC-L than CPVI alone. In realistic in silico biatrial modeling, which reflected the electroanatomies of 10 patients, SVC-L significantly reduced biatrial dominant frequency compared with CPVI alone (P<0.001) and increased AF termination and defragmentation rates (P=0.033). Conclusions SVC-L ablation in addition to CPVI significantly improved the long-term rhythm outcome over 2 years after AF catheter ablation by mechanisms involving autonomic modulation and AF organization.

Electroporation of epicardial autonomic ganglia: Safety and efficacy in medium-term canine models.

BACKGROUND: Endocardial radiofrequency ablation of epicardial ganglionic plexus (GP) for atrial fibrillation (AF) is complicated by myocardial damage. OBJECTIVES: We hypothesized that an epicardial approach with a novel nitinol catheter system capable of causing irreversible electroporation (IRE) with direct current (DC) could selectively and permanently destroy GP without collateral myocardial injury. METHODS: Acute studies and medium-term terminal studies (mean survival, 1137 days) were performed with seven dogs. In the acute studies, DC was used to target epicardial GP within the transverse sinus, oblique sinus, vein of Marshall, and right periaortic space. Successful electroporation was defined as the presence of ablative lesions in the GP without collateral myocardial damage. A four-point integer system was used to classify histologic changes in tissue harvested from the ablation sites. Atrial effective refractory period (AERP) was measured during the acute and medium-term studies. RESULTS: For six dogs in the medium-term studies, the postablation period was uneventful without complications. Lesions were successfully created at 20 of 21 sites (95.2%) with more than minimal myocardial damage in one dog. An increase in AERP occurred in both atria during the acute studies but was maintained only in the right atrium at medium-term follow-up (5032 milliseconds). No dog had damage to the esophagus, adjacent great arteries, or pulmonary veins. CONCLUSIONS: This proof-of-concept study suggests that safe, effective, and selective epicardial ablation of GP can be performed with DC by IRE with minimal collateral myocardial damage.

Histological characteristics of eosinophilic myenteric ganglionitis: an under-recognised cause of chronic intestinal pseudo-obstruction.

Eosinophilic myenteric ganglionitis (EMG) is characterised by eosinophilic infiltration of the myenteric plexus. EMG has been rarely reported as a cause of chronic intestinal pseudo-obstruction (CIPO), and its histopathological features are not fully elucidated. We analysed seven patients with CIPO. Three of them were diagnosed with EMG and four patients were categorised as non-EMG. Clinicopathological features were similar in both groups. These features included subtle to mild lymphocytic infiltration at the myenteric ganglia/muscularis propria, loss of myenteric ganglions and interstitial cells of Cajal (ICC), and no significant findings in the mucosa. The exceptions were moderate to severe degree of eosinophilic infiltration at the myenteric ganglia/muscularis propria in EMG. Functional gastrointestinal obstruction may be associated with inflammatory cell infiltration at the myenteric ganglia/muscularis propria, leading to subsequent hypoganglionosis and deficiency of ICC in EMG. Pathologists and clinicians should be aware of this distinction during differential diagnosis of patients with CIPO.

Selective ablation of atrial ganglionated plexus attenuates vasovagal reflex in a canine model.

BACKGROUND: Atrial ganglionated plexus (GP) ablation was proved to have therapeutic effects on vasovagal syncope. The study aimed to investigate whether selective ablation of only right anterior GP (ARGP) and right inferior GP (IRGP) was effective in a canine model of vasovagal syncope. METHODS: Seventeen mongrel dogs were divided into control (N = 10) and ablation group (N = 7). Bilateral thoracotomy was performed at the fourth intercostal space and ARGP and IRGP were ablated in the ablation group. A bolus of veratridine (15 ug/kg) was injected into the left atrium to induce vasovagal reflex. Surface electrocardiogram and blood pressure (BP) were continuously monitored. Heart rate (HR) variability was calculated to represent cardiac autonomic tone. RESULTS: Veratridine injection induced vasovagal reflex in all dogs. HR decreased from 149 ± 17 to 89 ± 33 beats/min (P < 0.001) in the control group, while in the ablation group HR decreased from 141 ± 35 to 125 ± 34 beats/min (P = 0.032). The postveratridine HR in the ablation group was significantly higher than that in the control group (P = 0.045). A significantly less intense HR decrease was observed in the ablation group compared with control (-17 ± 16 vs -61 ± 34 beats/min, P = 0.006). Significant BP decreases were induced in both the groups (all P < 0.01), while no evident differences in postveratridine BP and the extent of BP decreases were found between the groups. HR variability revealed significant decrease in cardiac vagal tone after ablation [high-frequency power, 0.50 (0.17-1.05) vs 6.28 (0.68-8.99) ms2 , P = 0.005]. CONCLUSIONS: Selective ablation of ARGP + IRGP weakened cardiac parasympathetic control and significantly attenuated the cardioinhibitory response in an animal model of vasovagal reflex. This ablation strategy might be effective for vasovagal syncope with evident cardioinhibitory response.

Quality of life improves after thoracoscopic surgical ablation of advanced atrial fibrillation: Results of the Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery (AFACT) study.

OBJECTIVE: We evaluated health-related quality of life at 12 months after thoracoscopic surgical ablation in patients enrolled in the Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery study. The Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery study assessed the efficacy and safety of ganglion plexus ablation in patients with symptomatic advanced atrial fibrillation undergoing thoracoscopic surgical ablation. METHODS: Patients (n = 240) underwent thoracoscopic pulmonary vein isolation with additional ablation lines in patients with persistent atrial fibrillation. Subjects were randomized to additional ganglion plexus ablation or control. Short Form 36 quality of life questionnaires were collected at baseline and at 6 and 12 months of follow-up. RESULTS: A total of 201 patients were eligible for quality of life analysis (age 59 ± 8 years, 72% were men, 68% had an enlarged left atrium, 57% had persistent atrial fibrillation). Patients improved in physical and mental health at 6 months (both P < .01) and 12 months (both P < .01) relative to baseline, with no difference between the ganglion plexus (n = 101) and control (n = 100) groups. Short Form 36 subscores in patients with 1 or no atrial fibrillation recurrences were similar to those in the general Dutch population after 12 months. Patients with multiple atrial fibrillation recurrences (30%) improved in mental (P < .01), but not physical health, and 6 of 8 Short Form 36 subscales remained below those of the general Dutch population. Patients with irreversible, but not with reversible procedural complications had persistently diminished quality of life scores at 12 months. CONCLUSIONS: Thoracoscopic surgery for advanced atrial fibrillation results in improvement in quality of life, regardless of additional ganglion plexus ablation. Quality of life in patients with no or 1 atrial fibrillation recurrence increased to the level of the general Dutch population, whereas in patients with multiple atrial fibrillation recurrences quality of life remained lower. Irreversible but not reversible procedural complications were associated with persistently lower quality of life.

Heart rate variability after radiofrequency ablation of epicardial ganglionated plexuses on the ovine left atrium.

BACKGROUND: Ganglionated plexuses (GP) are terminal parts of cardiac autonomous nervous system (ANS). Radiofrequency ablation (RFA) for atrial fibrillation (AF) possibly affects GP. Changes in heart rate variability (HRV) after RFA can reflect ANS modulation. METHODS: Epicardial RFA of GP on the left atrium (LA) was performed under the general anesthesia in 15 mature Romanov sheep. HRV was used to assess the alterations in autonomic regulation of the heart. A 24 - hour ECG monitoring was performed before the ablation, 2 days after it and at each of the 12 following months. Ablation sites were evaluated histologically. RESULTS: There was an instant change in HRV parameters after the ablation. A standard deviation of all intervals between normal QRS (SDNN), a square root of the mean of the squared differences between successive normal QRS intervals (RMSSD) along with HRV triangular index (TI), low frequency (LF) power and high frequency (HF) power decreased, while LF/HF ratio increased. Both the SDNN, LF power and the HF power changes persisted throughout the 12 - month follow - up. Significant decrease in RMSSD persisted only for 3 months, HRV TI for 6 months and increase in LF/HF ratio for 7 months of the follow - up. Afterwards these three parameters were not different from the preprocedural values. CONCLUSIONS: Epicardial RFA of GP's on the ovine left atrium has lasting effect on the main HRV parameters (SDNN, HF power and LF power). The normalization of RMSSD, HRV TI and LF/HF suggests that HRV after epicardial RFA of GPs on the left atrium might restore over time.

Efficacy of ganglionated plexi ablation in addition to pulmonary vein isolation for paroxysmal versus persistent atrial fibrillation: a meta-analysis of randomized controlled clinical trials.

PURPOSE: Adjunctive ganglionated plexi (GP) ablation may improve success rates for treatment of atrial fibrillation (AF) when combined with pulmonary vein (PV) isolation. Existing meta-analyses on GP ablation have included observational studies and have not incorporated more recent randomized clinical trial data. Moreover, the impact of AF subtype (paroxysmal vs. persistent) on outcomes of GP ablation has not been well established. METHODS: We performed a meta-analysis of randomized controlled trials (RCTs) comparing GP ablation + pulmonary vein (PV) isolation versus PV isolation alone according to the subtype of AF. The primary endpoint was freedom from sustained AF or atrial tachyarrhythmia (AT) after a single procedure. RESULTS: Across four RCTs, 718 patients (358 and 360 that underwent GP ablation + PV isolation [intervention] vs. PV isolation alone [control], respectively) were included in the study. Mean left atrial size and left ventricular ejection fraction were 45.7 mm and 54.8%, respectively. Among paroxysmal AF patients, GP ablation was linked to significantly higher freedom from AT/AF (75.8 vs. 60.0% for the intervention vs. control arms respectively; OR [95% CI]: 2.22 [1.36-3.61], P = 0.001). Among persistent AF patients, GP ablation was associated with a non-significant trend towards higher rates of freedom from AT/AF (54.7 vs. 43.3% for the intervention vs. control arms respectively; OR [95% CI]: 1.55 [0.96-2.52], P = 0.08). In all cases, heterogeneity was found to be low (I 2 of 32% or lower). CONCLUSIONS: Compared to PV isolation alone, GP ablation + PV isolation is associated with better outcomes in patients with paroxysmal AF and without significant structural heart disease.

Assessment of the effect of left atrial cryoablation enhanced by ganglionated plexi ablation in the treatment of atrial fibrillation in patients undergoing open heart surgery.

BACKGROUND: The aim of our study was to investigate, whether enhancement of left atrial cryoablation by ablation of the autonomic nervous system of left atrium leads to influencing the outcomes of surgical treatment of atrial fibrillation in patients with structural heart disease undergoing open-heart surgery. METHODS: The observed patient file consisted of 100 patients, who have undergone a combined open-heart surgery at our department between July 2012 and December 2014. The patients were indicated for the surgical procedure due to structural heart disease, and suffered from paroxysmal, persistent, or long-standing persistent atrial fibrillation. In all cases, left atrial cryoablation was performed in the extent of isolation of pulmonary veins, box lesion, connecting lesion with mitral annulus, amputation of the left atrial appendage and connecting lesion of the appendage base with left pulmonary veins. Furthermore, 35 of the patients underwent mapping and radiofrequency ablation of ganglionated plexi, together with discision and ablation of the ligament of Marshall (Group GP). A control group was consisted of 65 patients without ganglionated plexi intervention (Group LA). The main primary outcome was establishment and duration of sinus rhythm in the course of one-year follow-up. RESULTS: Evaluation of the number of patients with a normal sinus rhythm in per cent has shown comparable values in both groups (Group GP - 93.75%, Group LA - 86.67%, p = 0.485); comparable results were also observed in patients with normal sinus rhythm without anti-arrhythmic treatment in the 12th month (Group GP - 50%, Group LA - 47%, p = 0.306). We have not observed any relation between the recurrence of atrial fibrillation and the presence of a mitral valve surgery, or between the presence of a mitral and tricuspid valves surgery and between the left atrial diameter > 50 mm. CONCLUSIONS: Enhancement of left atrial cryoablation by gangionated plexi ablation did not influence the outcomes of surgical ablation due to atrial fibrillation in our population in the course of 12-month follow-up. TRIAL REGISTRATION: The study was approved retrospectively by the Ethics Committee of the University Hospital Ostrava ( reference number 867/2016).