Ganglionated Plexi Ablation Research Articles

Acute change in parasympathetic cardiac innervation after pulmonary vein isolation by pulse-field and radiofrequency energy

Abstract Background In patients with atrial fibrillation (AF), pulmonary vein isolation (PVI) by radiofrequency (RF) energy is associated with a significant change of cardiac autonomic regulations due to collateral ganglionic plexi ablation. Pulse-field (PF) ablation energy presumably spares neural tissue. Purpose We compared the effect of PVI by PF and RF energy on cardiac autonomic function. Methods A study enrolled 23 patients who underwent PVI in general anaesthesia. In 12 patients, a novel lattice-tip catheter and PF energy were used for ablation while 11 patients were ablated using a conventional irrigated-tip catheter and RF energy. The response of the sinus node (SAN) and atrioventricular node (AVN) to extracardiac high-frequency vagal stimulation (ECVS) was tested before and after PVI (via right internal jugular vein; stimulation frequency of 50 Hz; pulse width of 0.05 ms; output of 1 V/kg (<70V); train duration of 5 s). Results At baseline, physiological massive response to ECVS (sinus arrest and/or AV block) was demonstrated in the majority of patients. After PVI, complete loss of autonomic response of the SAN in 11/11 (100%) and 3/12 (25%) patients (p=0.003), and the AVN in 9/11 (82%) and 3/12 (25%) patients (p=0.01) was observed in RF and PF groups, respectively. The figure shows the maximum duration of the pause in sinus rhythm (maximum P-P interval) and AVN block (maximum R-R interval during atrial pacing) induced by ECVS after PVI. Conclusion Cardiac vagal response is preserved in a considerable proportion of AF patients after PF ablation which is in contrast with a significantly stronger effect of RF energy. This may influence the clinical outcome of AF ablation procedures. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Institute for Clinical and Experimental Medicine, Prague

Long-term Success of Partial Ganglionated Plexus Ablation in a Patient with Tachycardia-bradycardia Syndrome and Syncope: Whom and How?

Long-term Success of Partial Ganglionated Plexus Ablation in a Patient with Tachycardia-bradycardia Syndrome and Syncope: Whom and How?

Location of Parasympathetic Innervation Regions From Electrograms to Guide Atrial Fibrillation Ablation Therapy: An in silico Modeling Study.

The autonomic nervous system (ANS) plays an essential role in the generation and maintenance of cardiac arrhythmias. The cardiac ANS can be divided into its extrinsic and intrinsic components, with the latter being organized in an epicardial neural network of interconnecting axons and clusters of autonomic ganglia called ganglionated plexi (GPs). GP ablation has been associated with a decreased risk of atrial fibrillation (AF) recurrence, but the accurate location of GPs is required for ablation to be effective. Although GP stimulation triggers both sympathetic and parasympathetic ANS branches, a predominance of parasympathetic activity has been shown. This study aims was to develop a method to locate atrial parasympathetic innervation sites based on measurements from a grid of electrograms (EGMs). Electrophysiological models representative of non-AF, paroxysmal AF (PxAF), and persistent AF (PsAF) tissues were developed. Parasympathetic effects were modeled by increasing the concentration of the neurotransmitter acetylcholine (ACh) in randomly distributed circles across the tissue. Different circle sizes of ACh and fibrosis geometries were considered, accounting for both uniform diffuse and non-uniform diffuse fibrosis. Computational simulations were performed, from which unipolar EGMs were computed in a 16 × 1 6 electrode mesh. Different distances of the electrodes to the tissue (0.5, 1, and 2 mm) and noise levels with signal-to-noise ratio (SNR) values of 0, 5, 10, 15, and 20 dB were tested. The amplitude of the atrial EGM repolarization wave was found to be representative of the presence or absence of ACh release sites, with larger positive amplitudes indicating that the electrode was placed over an ACh region. Statistical analysis was performed to identify the optimal thresholds for the identification of ACh sites. In all non-AF, PxAF, and PsAF tissues, the repolarization amplitude rendered successful identification. The algorithm performed better in the absence of fibrosis or when fibrosis was uniformly diffuse, with a mean accuracy of 0.94 in contrast with a mean accuracy of 0.89 for non-uniform diffuse fibrotic cases. The algorithm was robust against noise and worked for the tested ranges of electrode-to-tissue distance. In conclusion, the results from this study support the feasibility to locate atrial parasympathetic innervation sites from the amplitude of repolarization wave.

B-PO05-138 CATHETER ABLATION OF ATRIAL FIBRILLATION IS NOT ASSOCIATED WITH DESTRUCTION OF CARDIAC AFFERENTS DRIVING VOLUME-REGULATING AUTONOMIC REFLEXES

We have previously shown abnormal cardiac volume-sensitive reflexes (whose receptors are co-located in veno-atrial tissue) in AF patients. Whether unintended nerve disruption from Pulmonary Vein Isolation (PVI) could also occur is unknown. To evaluate whether PVI disrupts afferent volume-sensitive reflexes. We consecutively studied paroxysmal/persistent AF patients pre-PVI (n =18) and recontacted them for a post-PVI visit. We excluded those with AF recurrence/procedural complications, allowing redo procedures if AF-free >6 months. A cohort of 9 patients consented to both visits. We measured beat-to-beat mean arterial pressure (MAP) and heart rate (HR) continuously while testing reflex vasoconstriction from Lower Body Negative Pressure (LBNP), which offloads veno-atrial volume receptors, using forearm blood flow (FBF∝1/vascular resistance), at 0, -20 & -40 mmHg LBNP by venous occlusion plethysmography. We withheld anti-hypertensives/arrhythmics (5 half-lives). Mean age was 64±3 years; 78% male; BMI 28±1 kg/m2; LA size 37±2 ml/m2; and left ventricular function 65±3 %. We performed single ring radiofrequency PVI (PV and posterior wall, n=7); cryoablation (n=1) and wide antral PVI (n=1). Redo in n=2. During LBNP, MAP decreased slightly both pre (-1.6±3%) and post-PVI (-2.8±1.8%); P=0.7. HR increased similarly (P=0.7) pre (10.6±6.4%) and post-PVI (7.2±1.5%). FBF was unchanged (P=0.8), Figure. The reflex response to decreased cardiac volume is not altered by PVI. More work to assess other lesion sets or ganglionated plexi ablation is needed to ensure absence of adverse autonomic remodelling due to catheter ablation for AF.

Effect of ganglionated plexi ablation by high-density mapping on long-term suppression of paroxysmal atrial fibrillation - The first clinical survey on ablation of the dorsal right plexusus.

BackgroundLong-term outcomes of suppressing paroxysmal atrial fibrillation (PAF) with additive ganglionated plexus (GP) ablation (GPA) remains unknown.ObjectivesThe aim of the study is to assess potential role of additional GPA for PAF suppression.MethodsThis study consisted of 225 patients; 68 (group A: 58 male, aged 60 ± 11 years) underwent pulmonary vein isolation (PVI) alone and 157 (group B: 137 male, aged 61 ± 11 years) GPA followed by PVI. GPA was performed based on the high-density mapping with high-frequency stimulation (HFS) delivered to left atrial (LA) major GP. The latter 85 group B patients (54%) underwent ablation to a posteromedial area within superior vena cava as a part of dorsal right atrial GP (SVC-Ao GP).ResultsIn group B, HFS was applied to 126 ± 32 sites, with a median of 47 GP sites (40.0%) being ablated. In patients undergoing an SVC-Ao GPA, HFS and the SVC-Ao GPA were applied at a median of 15 and 4 sites (29.4%), respectively. The PVI with a GPA provided higher PAF suppression than a PVI alone during more than 4 years of follow-up (56.7% vs 38.2%, odds ratio: 0.42, 95% confidence interval: 0.23–0.76, P < .05), but the SVC-Ao GPA did not provide further suppressive effects. Multivariate analyses revealed that tachycardia-bradycardia syndrome and non-PV foci were independent predictors of PAF recurrence after PVI with a GPA (P < .01).ConclusionGPA to LA major GP by high-density mapping provides long-term benefits for PAF suppression over 4 years of follow-up, but the effect of an empiric SVC-Ao GPA could not be appreciated, suggesting little effect on suppressing non-PV foci.

Effect of conscious sedation and deep sedation on the vagal response characteristics during ganglionated plexus ablation.

We aimed to determine the effects of conscious and deep sedation on vagal response (VR) characteristics during ganglionated plexus (GP) ablation. Forty consecutive patients undergoing GP ablation for vasovagal syncope were divided to receive conscious sedation with midazolam (Group 1, n = 29) or deep sedation with the midazolam-propofol combination (Group 2, n = 11). VR was defined on three levels. R-R interval increase of >50% (Level 1); R-R interval increase of 20%-50% (Level 2); and R-R interval increase of <20% (Level 3). The ratio of Level 1 VR during ablation on left superior and inferior GPs was significantly lower in Group 2 (p < .0001 and p = .034, respectively). Once the cut-off for VR was decreased to Level 2, the ratio of (+) VR was similar between groups during ablation of left-sided GPs. Positive VR in any level was lower than 20% during ablation of right-sided GPs. The autonomic tone might be affected in different ways by the level or type of intravenous sedation. Awareness of anesthesia-related differences may be important if GP ablation will be performed by using VR characteristics during ablation.

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

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. 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. 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). 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.

The impacts of the ganglionated plexus ablation sequence on the vagal response, heart rate, and blood pressure during cardioneuroablation.

Cardioneuroablation is an emerging and promising therapy to treat vasovagal syncope (VVS). The aim of this study was to assess the characteristics of vagal response (VR), heart rate (HR), and blood pressure (BP) during cardioneuroablation with different sequences of ganglionated plexus (GPs) catheter ablation and clarify the regulatory mechanism of cardiac GPs of the left atrium. A total of 28 patients with VVS who underwent cardioneuroablation were prospectively enrolled and randomly assigned to 2 groups according to the ablation order of GPs. Group A: Left superior GP (LSGP) - Left inferior GP (LIGP) - Right inferior GP (RIGP) - Right anterior GP (RAGP); Group B: RAGP - LSGP - LIGP - RIGP. In Group A, the VR in LSGP, LIGP, RIGP, and RAGP during ablation was observed in 11 (78.6%), 5 (35.7%), 4 (28.6%) and 2 (14.3%) cases, respectively. In contrast, in Group B, the VR in RAGP, LSGP, LIGP, and RIGP was observed in 2 (14.3%), 1 (7.1%), 0 (0%) and 0 (0%) cases, respectively. BP reduction during procedure was observed eight times in Group A and once in Group B (P=0.013). In both groups, the HR increased significantly during ablation of the RAGP (all P<0.001). The sequence of GPs ablation during cardioneuroablation affected the occurrence rate of VR and BP reduction during cardioneuroablation. The RAGP was a critical target to increase HR and inhibit VR and BP reduction during procedure, indicating that it may be a key GP in regulation of the cardiac vagal activity.

Open-Chest Pulsed Electric Field Ablation of Cardiac Ganglionated Plexi in Acute Canine Models

Objectives: This study aimed to evaluate the safety and acute effect on markers of cardiac autonomic tone following pulsed electric fields (PEF) delivered to epicardial ganglionated plexi (GP) during a cardiac surgical procedure. Background: Ablation of GP as a treatment for atrial fibrillation (AF) has shown promise but thermal ablation energy sources are limited by risk of inadvertent collateral tissue injury. Methods: In acute canine experiments, median sternotomy was performed to allow identification of 5 epicardial GP regions using an anatomy-guided approach. Each site was targeted with saline-irrigated PEF (1000 V, 100 µs, 10 ECG-synchronized pulse sequences). Atrial effective refractory period (AERP) and local electrogram (EGM) amplitude were measured before and after each treatment. Histology was performed post-treatment from samples of treatment adjacent structures. Results: In 5 animals, 30 (n=2) and 60 (n=3) pulses were successfully delivered to all 5 target sites). There was no difference in local atrial EGM amplitude before and after PEF at each site (1.83{plus minus}0.41 mV vs. 1.92{plus minus}0.53 mV; p = 0.72). Mean AERP increased from 97 {plus minus} 15 ms at baseline to 115 {plus minus} 7 ms following treatment at all sites (18.6% increase, 95% CI [1.9-35.2%]; p = 0.037). There were no sustained ventricular arrhythmias or acute evidence of ischemia following delivery. Histology showed complete preservation of adjacent atrial myocardium, phrenic nerves, pericardium, and esophagus. Conclusions: The use of PEF to target regions rich in cardiac GP in open-chest canine experiments was feasible and effective at acutely altering markers of cardiac autonomic tone.

Effect of general and local anesthesia on the vagal response characteristics during ganglionated plexus ablation

Abstract Funding Acknowledgements Type of funding sources: None. Background The effect of different anesthetics on the function of the autonomic nervous system (ANS) is not well known. As a relatively new treatment option, ganglionated plexus (GP) ablation aims to modify the behavior of the cardiac ANS to prevent some/all of the autonomic processes occurring in vasovagal syncope (VVS) by using endocardial ablation techniques. Purpose The purpose of this study was to determine the effects midazolam and propofol on the vagal response (VR) characteristics during GP ablation in patients with vasovagal syncope (VVS). Methods Forty consecutive patients undergoing GP ablation for VVS were divided to receive local anesthesia with midazolam (group 1, n = 29) or general anesthesia with propofol (group EA, n = 11). All GP sites were detected by using previously defined fragmented electrogram based strategy. VR was defined on 3 levels: 1) R-R interval increased by 50% (level 1); 2) R-R interval increased by 20-50% (level 2); and 3) R-R interval increase lower than 20% (level 3). Results Baseline characteristics and mean follow-up times were comparable between groups. In both groups, the left superior GP (LSGP) was the most common GP site at which a VR was observed. However, there was a significant difference between groups for level of VR. While ablation on the LSGP caused a level 1 VR in 89.6% of cases in group 1, level 1 VR was seen in 22.2% of cases in group 2 (p &amp;lt; 0.0001). Similarly, ratio of level 1 VR during ablation on the left inferior GP (LIGP) was significantly lower in group 2 (44.8% vs 9%, p = 0.034). Once cut-off for VR was decreased to level 2, the ratio of (+) VR increased to 90.9% during ablation on the LSGP in group 2. Level 2 VR was detected in 45.4% of cases during ablation on the LIGP. Ratio of positive VRs in any level was lower than 20% during ablation on the right superior and inferior GPs in both groups. During a mean follow-up time of 12.1 ± 7 months, all but 2 (5%) of 40 patients were free of syncope. Conclusions The autonomic nervous tone might be affected in different ways by local and general anesthesia. Propofol may reveal a shift in the sympathovagal balance toward sympathetic predominance which may cause a blunting on VR during GP ablation. Further randomized, controlled and multicenter studies should be performed to confirm these findings.

Potential value of the low frequency/high frequency ratio of heart rate variability to guide atrial fibrillation ablation procedures

Abstract Funding Acknowledgements Type of funding sources: None. Background. The differentiation between vagally and non-vagally mediated atrial fibrillation (AF) could be useful to decide adding ganglionated plexi ablation (GPA) to pulmonary vein isolation (PVI) in patients with vagally mediated AF onset. The role of the autonomic nervous system in triggering paroxysmal AF can be analyzed through heart rate variability (HRV) parameters. The low frequency/high frequency ratio (LF/HF) is used as an index of sympatho-vagal interaction. Based on clinical criteria, values of LF/HF &amp;lt;1.5 are considered to reflect an increase of vagal modulation. Purpose Identify patients with paroxysmal AF who may benefit from GPA in addition to PVI, based on analysis of HRV parameters Material and methods From our database of unselected Holter recordings containing paroxysmal AF episodes, 199 analyzable AF onsets were labelled. We analyzed HRV frequential parameters by segments every 300 RR intervals to identify adrenergic and vagal onsets of AF episodes. We categorized AF onsets, depending of their respective values of LF/HF. We also checked the relationship of these parameters to heart rate (HR). We followed the evolution of the mean normalized values of LF/HF from the beginning of the recordings to the AF onsets (see figure). Results We found a progressive increase of LF/HF in normalized units (mean [95% confidence interval]) from 2.44 [2.12-2.76] to 3.12 [2.85-3.39] in the adrenergic group (n = 113) and a progressive decrease of LF/HF from 1.51 [1.28-1.75] to 1.02 [0.95-1.09] in the vagal group (n = 86). Differences between adrenergic and vagal AF were highly significant using Mann-Whitney test (p &amp;lt; 0.001). A given patient shows the same type of AF in 80% of cases. We found no correlation between frequential parameters and HR. Conclusions Our data show potential added value of frequential HRV analysis to guide additional ganglionated plexi ablation to PVI. This remains to be demonstrated in a prospective study. The ratio LF/HF should be considered to optimize the decision-making process for the ablation procedure. Abstract Figure. Frequential HRV parameters before AF

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

Effects of pulse field and radiofrequency pulmonary vein isolation on parasympathetic cardiac innervation

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): IKEM Background Pulmonary vein isolation (PVI) is an established treatment modality for patients with atrial fibrillation (AF). PVI performed by radiofrequency (RF) energy results in parasympathetic denervation of the heart by collateral ganglionic plexi ablation. Pulse field (PF) is a novel nonthermal energy source for PVI that selectively ablates atrial myocardium while preserving cardiac autonomic nerves, which may affect the outcome after PVI. Purpose The study compared the effect of PVI between RF and PF ablation on cardiac autonomic function and a short-term AF recurrence rate. The resting heart rate (HR) was evaluated as a simple index of sinus nodal parasympathetic innervation. Methods We investigated 45 patients (aged 64 ± 7 years, 4 women) who underwent PVI by novel three-dimensional electroanatomical mapping/ablation system (lattice electrode ablation system). PVI was performed by either high-energy RF (n = 21) or PF (n = 24) energy using the identical ablation catheter. Resting HR assessed by standard ECG was recorded the day before the procedure and at the 3-month visit. Arrhythmia recurrences were analysed by 24-Holter at the 3-month visit. Results All PVs were acutely isolated in all patients. The HR data are shown in the Table. The baseline HR did not differ between both groups. A significant increase in HR was observed only in the RF ablation subgroup. The between-group difference remained significant even after adjustment for age, gender, and baseline HR. There was no difference in arrhythmia recurrences at the 3-month visit between study groups. Conclusions Parasympathetic denervation effects on HR after the PF ablation are virtually absent. Comparable AF recurrence rate at 3-month visit after RF and PF ablation suggests that preservation of autonomic innervation has no impact on AF recurrence during short-term follow-up. Table RF PVI (n = 21) PF PVI (n = 24) P Baseline HR (bpm) 60.0 ± 7.1 63.8 ± 9.4 n.s. HR change - 3-month visit (bpm) 14.4 ± 6.9 0.3 ± 8.6 P &amp;lt;0.001 Arrhythmia recurrences 3/21 (14%) 2/24 (8%) n.s.

Neuroscientific therapies for atrial fibrillation.

The cardiac autonomic nervous system (ANS) plays an integral role in normal cardiac physiology as well as in disease states that cause cardiac arrhythmias. The cardiac ANS, comprised of a complex neural hierarchy in a nested series of interacting feedback loops, regulates atrial electrophysiology and is itself susceptible to remodelling by atrial rhythm. In light of the challenges of treating atrial fibrillation (AF) with conventional pharmacologic and myoablative techniques, increasingly interest has begun to focus on targeting the cardiac neuraxis for AF. Strong evidence from animal models and clinical patients demonstrates that parasympathetic and sympathetic activity within this neuraxis may trigger AF, and the ANS may either induce atrial remodelling or undergo remodelling itself to serve as a substrate for AF. Multiple nexus points within the cardiac neuraxis are therapeutic targets, and neuroablative and neuromodulatory therapies for AF include ganglionated plexus ablation, epicardial botulinum toxin injection, vagal nerve (tragus) stimulation, renal denervation, stellate ganglion block/resection, baroreceptor activation therapy, and spinal cord stimulation. Pre-clinical and clinical studies on these modalities have had promising results and are reviewed here.

Size matters in atrial fibrillation: the underestimated importance of reduction of contiguous electrical mass underlying the effectiveness of catheter ablation.

Evidence has accumulated over the last century of the importance of a critical electrical mass in sustaining atrial fibrillation (AF). AF ablation certainly reduces electrically contiguous atrial mass, but this is not widely accepted to be an important part of its mechanism of action. In this article, we review data showing that atrial size is correlated in many settings with AF propensity. Larger mammals are more likely to exhibit AF. This is seen both in the natural world and in animal models, where it is much easier to create a goat model than a mouse model of AF, for example. This also extends to humans—athletes, taller people, and obese individuals all have large atria and are more likely to exhibit AF. Within an individual, risk factors such as hypertension, valvular disease and ischaemia can enlarge the atrium and increase the risk of AF. With respect to AF ablation, we explore how variations in ablation strategy and the relative effectiveness of these strategies may suggest that a reduction in electrical atrial mass is an important mechanism of action. We counter this with examples in which there is no doubt that mass reduction is less important than competing theories such as ganglionated plexus ablation. We conclude that, when considering future strategies for the ablative therapy of AF, it is important not to discount the possibility that contiguous electrical mass reduction is the most important mechanism despite the disappointing consequence being that enhancing success rates in AF ablation may involve greater tissue destruction.

Symptomatic Premature Ventricular Contractions in Vasovagal Syncope Patients: Autonomic Modulation and Catheter Ablation.

IntroductionThere has been limited reports about the comorbid premature ventricular contractions (PVCs) and vasovagal syncope (VVS). Deceleration capacity (DC) was demonstrated to be a quantitative evaluation to assess the cardiac vagal activity. This study sought to report the impact of autonomic modulation on symptomatic PVCs in VVS patients.Methods and ResultsTwenty-six VVS patients with symptomatic idiopathic PVCs were consecutively enrolled. Identification and catheter ablation of left atrial ganglionated plexi (GP) and PVCs were performed in 26 and 20 patients, respectively. Holter 24 h-electrocardiograms were performed before and after the procedure to evaluate DC and PVCs occurrence. Eighteen patients were subtyped as DC-dependent PVCs (D-PVCs) and eight as DC-independent PVCs groups (I-PVCs). In D-PVCs group, circadian rhythm of hourly PVCs was positively correlated with hourly DC (P < 0.05) while there was no correlation in I-PVCs group (P > 0.05). Fifty-three GPs with positive vagal response were successfully elicited (2.0 ± 0.8 per patient). PVCs failed to occur spontaneously nor to be induced in six patients. In the remaining 20 patients, PVCs foci identified were all located in the ventricular outflow tract region. Post-ablation DC decreased significantly from baseline (P < 0.05). During mean follow-up of 10.64 ± 6.84 months, syncope recurred in one patient and PVCs recurred in another. PVCs burden of the six patients in whom neither catheter ablation nor antiarrhythmic drugs were applied demonstrated a significant decrease during follow-up (P = 0.037).ConclusionAutonomic activities were involved in the occurrence of symptomatic idiopathic PVCs in some VVS patients. D-PVCs might be facilitated by increased vagal activities. Catheter ablation of GP and PVCs foci may be an effective, safe treatment in patients with concomitant VVS and idiopathic PVCs.

The anatomical basis behind the neuromodulation effects associated with pulmonary vein isolation.

The anatomical basis underlying the neuromodulation effects seen with pulmonary vein (PV) isolation (PVI) is not fully understood. Left atrial (LA) electro-anatomical maps of 38 patients who underwent catheter cardioneuroablation for vagally mediated bradycarrhythmias were studied. During the procedure, LA ganglionic plexi (GPs) were systematically identified and ablated. Design PVI lines were created on these maps by a blinded observer, and the degree of overlap between four GPs and individual PVs was assessed. Here, 1.7 ± 7 (35.5 ± 17.0%) of the total 31.6 ± 10 GP ablation sites per patient were found to overlap with the design PVI lines. The overlap was higher for the right-sided GPs, p < .001. The degree of GP-PV overlap varied: 1 PV in 5 (13.2%) patients, 2 PVs in 15 (39.2%), 3 PVs in 16 (42.1%), and all 4 PVs in 2 (5.3%). No patient had zero GP-PV overlap. A vagal response was most commonly observed during ablation at the left superior GP (89.5%), while a sympathetic response was observed most often during the right superior GP ablation (97.4%). Some degree of GP-PV antral overlap is the norm, and this is more pronounced for the right-sided PVs. There is significant individual variability in the degree of overlap which may explain why neuromodulation effects are not seen universally following PVI.

Ganglionated Plexi Ablation Suppresses Chronic Obstructive Sleep Apnea-Related Atrial Fibrillation by Inhibiting Cardiac Autonomic Hyperactivation.

Background: Previous studies have reported that right pulmonary artery ganglionated plexi (GP) ablation could suppress the onset of atrial fibrillation (AF) associated with obstructive sleep apnea (OSA) within 1 h.Objective: This study aimed to investigate the effect of superior left GP (SLGP) ablation on AF in a chronic OSA canine model.Methods and Results: Fifteen beagles were randomly divided into three groups: control group (CTRL), OSA group (OSA), and OSA + GP ablation group (OSA + GP). All animals were intubated under general anesthesia, and ventilation-apnea events were subsequently repeated 4 h/day and 6 days/week for 12 weeks to establish a chronic OSA model. SLGP were ablated at the end of 8 weeks. SLGP ablation could attenuate the atrial effective refractory period (ERP) reduction and decrease ERP dispersion, the window of vulnerability, and AF inducibility. In addition, chronic OSA leads to left atrial (LA) enlargement, decreased left ventricular (LV) ejection fraction, glycogen deposition, increased necrosis, and myocardial fibrosis. SLGP ablation reduced the LA size and ameliorated LV dysfunction, while myocardial fibrosis could not be reversed. Additionally, SLGP ablation mainly reduced sympathovagal hyperactivity and post-apnea blood pressure and heart rate increases and decreased the expression of neural growth factor (NGF), tyrosine hydroxylase (TH), and choline acetyltransferase (CHAT) in the LA and SLGP. After SLGP ablation, the nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway, cholesterol metabolism pathway, and ferroptosis pathway were notably downregulated compared with OSA.Conclusions: SLGP ablation suppressed AF in a chronic OSA model by sympathovagal hyperactivity inhibition. However, there were no significant changes in myocardial fibrosis.

QTc shortening effect of ganglionated plexi ablation.

In previous studies, patients undergoing ablation of ganglionated plexi (GPA) for vagally mediated bradyarrhythmias were noted to have shortening of their corrected QT interval (QTc). To compare the effects of GPA (group 1) to pulmonary vein isolation + GPA (group 2) on QTc. We enrolled 39 patients, n = 25 in group 1 and n = 14 in group 2. QTc was calculated at baseline, at 24 h after ablation, and at 9-12 months in the follow-up. Recurrent syncope, asystole >2 s, and/or second- or third-degree AVB episodes were carefully documented as the primary outcome in group 1. Any atrial arrhythmia ≥30 seconds documented on 24-h Holter monitoring was defined as the primary outcome in group 2. The mean follow-up time was 14.9 ± 4 months. Acute success was achieved in all cases. In whole cohort, a significant shortening on QTcBazett, QTcFramingham, QTcFredericia, and QTcHodges was observed [416 vs 398ms (p = .002), 411vs 378 ms (p < .001), 412 vs 379ms (p < .001), and 420 vs 383ms (p < .001), respectively]. In the linear mixed model analysis, the longitudinal reduction tendency in the QTc level was more pronounced in group 1. Event-free survival was detected in 90.7% (59/65) of cases. Our results demonstrate a significant shortening of QTc in addition to high medium-term success rates after GPA. Pulmonary vein isolation + GPA was associated with lower QTc shortening effect which implies structural disease may change electrophysiological response to ablation. The most likely mechanism is the effect of GPA on the sympathetic system.

Cardioneuroablation – Induced shift in sinus node activation: A new parameter of vagal denervation?

Experimental studies demonstrated a shift in the leading pacemaker site based on parasympathetic or sympathetic dominance. Radiofrequency catheter ablation of ganglionated plexi (GP) might be used to overcome deleterious effects of enhanced parasympathetic tone. Herein, we present two patients who underwent GP ablation due to cardioinhibitory type reflex syncope and symptomatic bradycardia, respectively. In both cases complete vagal denervation was achieved and was associated with a cranial shift of sinus node activation area with corresponding changes in surface P wave morphology. This unique phenomenon needs to be confirmed in the larger prospective study.