Ganglionated Plexi Research Articles

Comparative study of the therapeutic effects of radiofrequency ablation of ganglionated plexi guided by high-frequency stimulation and anatomical localization methods in the treatment of vagal syncope in young people.

To investigate the differences in safety and efficacy between high-frequency stimulation (HFS) and anatomically guided endocardial catheter ablation (AA) of the ganglionated plexi (GPs) for treating vasovagal syncope (VVS) in individuals engaged in high-intensity physical training. Forty-five patients (age 22.5 ± 4.4 years) undergoing high-intensity physical training were included from January 2020 to January 2023 at our hospital. Patients underwent GP ablation for recurrent syncope. Comprehensive evaluations, including head MRI, cardiac ultrasound, electrocardiogram (ECG), ambulatory ECG (Holter), ambulatory blood pressure monitoring, plate motion tests, and head-up tilt tests (HUT), were conducted to exclude other systemic disorders causing syncope. HFS and AA-guided GP ablation were performed on 10 and 35 patients, respectively, all of whom tested positive for HUT. Differences between the two groups were compared regarding ablation sites, ablation time, safety, and effectiveness. The ablation time was significantly shorter in the AA group compared to the HFS group (P < 0.001). The number of GPs selected for ablation using the AA method was reduced (P < 0.001). All patients in the HFS group experienced palpitations and discomfort, whereas only 31.43% of patients in the AA group reported these symptoms (P = 0.001). Fentanyl analgesia was administered in both groups, and no significant complications arose from the ablation. The longest follow-up duration was 52 months, while the shortest was 15 months. One case of pre-syncope occurred in the HFS group 8 months post-ablation, and one case of pre-syncope and two cases of syncope occurred in the AA group at 1 and 3 months post-ablation, respectively. There were no statistically significant differences in heart rate variability (HRV) and cardiac deceleration capacity (DC) between the two groups after ablation (P > 0.05). Two cases in the AA group still exhibited type II second-degree atrioventricular block during sleep. Both groups of patients were able to complete high-intensity physical training and showed significant symptom improvement post-ablation. Young individuals with VVS engaged in high-intensity physical training can benefit from GP ablation using both HFS and AA methods. The AA method requires relatively simple equipment, shorter procedure time, and results in less discomfort during the ablation.

Abstract 4145890: P-Wave Parameters on 12-Lead Electrocardiogram after Catheter Ablation: A Comparison between Pulsed Field Ablation and Cryoablation

Background: Catheter ablation (CA) is a well-established treatment for atrial fibrillation (AF). The most popular current methods of CA include radiofrequency ablation (RFA) and cryoablation (CRYO) which are thermal methods of ablation known to affect the autonomic nervous system through ablation of cardiac ganglionated plexi (GP). Pulsed[SC1] -field ablation (PFA) is a newer method of CA with demonstrated efficacy that preferentially affects cardiac cells and spares surrounding structures such as GP through irreversible electroporation which does not lead to chronic fibrosis like RFA or CRYO. Elevations in the marker the marker P terminal force (PTF) have been associated with AF/stroke and have been known to correlate with atrial fibrosis, and higher PTF after cryoablation for patients with paroxysmal AF has been associated with an increased risk of recurrence. The differences in P-wave parameters pre and post PFA have not been studied. Objective: To investigate the differences in P-wave parameters after PFA and compare them to CRYO. Methods: We identified 40 patients who underwent PFA (20 patients) or CRYO (20 patients) for paroxysmal AF and compared P-wave parameters including duration and amplitude in leads aVF, V1 and the PTF calculated as the duration x amplitude of the terminal negative component of the P-wave in V1. Data were obtained from 12-lead electrocardiograms obtained pre and post ablation. Results: The mean age of patients in our study was 61 with 75% male and 33% on antiarrythmics. We noticed a significant reduction in PTF for patients who underwent CRYO (54 mVmS at baseline compared to 36.8 mVmS after CRYO, p = 0.04) and no significant reduction in PTF for patients who underwent PFA (46 mVmS at baseline compared to 38 mVmS after PFA, p = 0.27). There was also a significant increase in HR after CRYO (65 bpm at baseline compared to 78 bpm after CRYO, p=0.01) and no significant change in HR after PFA (61 bpm at baseline compared with 60 bpm after PFA, p=0.8). There was no statistical difference in both groups looking at aVF or total V1 duration or amplitude pre and post ablation. Conclusions: CRYO leads to a significant change in PTF after ablation while PFA does not, consistent with the notion that PFA does not lead to fibrosis and PTF is not a useful marker for measuring risk of recurrence of AF post PFA.

Descriptive embryological insights of the colorectum of quail embryos with concern to its functional morphology

BackgroundQuail is an interesting emerging bird species gaining attention in developmental embryology research due to its small size, quick lifespan, and fast growth rate. These characteristics make quail an ideal model for examining the development of the gastrointestinal tract. Consequently, the embryonic development of the colorectum was conducted to provide a comprehensive understanding of its functions in digestion, absorption, and immunity.MethodologyThe morphological anatomy and microscopical structure of the colorectal wall of 74 embryos were studied using light and scanning electron microscopy (SEM). Histologically, the embryos were collected and dissected to extract the intestine. The samples were then fixed in 10% neutral buffer formalin for a minimum of 24 h, and in 2.5% glutaraldehyde buffer formalin for semithin processing and scanning electron microscopy.ResultsThe wall of the embryonic colorectum on the hatching day consisted of three layers; mucosa, muscularis externa, and serosa. Mucosa was a simple layer of columnar enterocytes interspersed with goblet cells that appeared as cub-like shaped cells. Additionally, two ganglionic plexuses were also developed in the colorectal wall; Auerbach plexus (among the colorectal tunica muscularis) and Meissner plexus (submucosal plexus).ConclusionThe morphological characteristics of the quail colorectum at different ages were closely related to its functional features.

The role of ganglionic plexi neurons in atrial fibrillation following spinal cord injury.

The role of ganglionic plexi neurons in atrial fibrillation following spinal cord injury.

Autonomic modulation impacts conduction velocity dynamics and wavefront propagation in the left atrium.

Atrial fibrosis and autonomic remodelling are proposed pathophysiological mechanisms in atrial fibrillation (AF). Their impact on conduction velocity (CV) dynamics and wavefront propagation was evaluated. Local activation times (LATs), voltage, and geometry data were obtained from patients undergoing ablation for persistent AF. LATs were obtained at three pacing intervals (PIs) in sinus rhythm (SR). LATs were used to determine CV dynamics and their relationship to local voltage amplitude. The impact of autonomic modulation- pharmacologically and with ganglionated plexi (GP) stimulation, on CV dynamics, wavefront propagation, and pivot points (change in wavefront propagation of ≥90°) was determined in SR. Fifty-four patients were included. Voltage impacted CV dynamics whereby at non-low voltage zones (LVZs) (≥0.5 mV) the CV restitution curves are steeper [0.03 ± 0.03 m/s ΔCV PI 600-400 ms (PI1), 0.54 ± 0.09 m/s ΔCV PI 400-250 ms (PI2)], broader at LVZ (0.2-0.49 mV) (0.17 ± 0.09 m/s ΔCV PI1, 0.25 ± 0.11 m/s ΔCV PI2), and flat at very LVZ (<0.2 mV) (0.03 ± 0.01 m/s ΔCV PI1, 0.04 ± 0.02 m/s ΔCV PI2). Atropine did not change CV dynamics, while isoprenaline and GP stimulation resulted in greater CV slowing with rate. Isoprenaline (2.7 ± 1.1 increase/patient) and GP stimulation (2.8 ± 1.3 increase/patient) promoted CV heterogeneity, i.e. rate-dependent CV (RDCV) slowing sites. Most pivot points co-located to RDCV slowing sites (80.2%). Isoprenaline (1.3 ± 1.1 pivot increase/patient) and GP stimulation (1.5 ± 1.1 increase/patient) also enhanced the number of pivot points identified. Atrial CV dynamics is affected by fibrosis burden and influenced by autonomic modulation which enhances CV heterogeneity and distribution of pivot points. This study provides further insight into the impact of autonomic remodelling in AF.

Cardioneural ablation-the first case series without the use of fluoroscopy.

Cardioneural ablation (CNA) and fluoroless ablation (FA) are emerging procedures and movements in contemporary in electrophysiology. Ablation of ganglionated plexus (GP) inputs in the atrium has been successfully targeted as a treatment for symptomatic bradyarrhythmias due to increased parasympathetic tone. As most of these patients are young, avoidance of ionizing radiation is of critical importance to limit potential long term deleterious effects. With widespread use of 3D electroanatomic mapping systems and advanced intracardiac echo (ICE) imaging, fluoroless ablation has become more widely adopted. However, fluoroless CNA has not been widely performed. The objective of this study is to demonstrate that CNA can be done safely and effectively without fluoroscopy. At a single-center, consecutive patients undergoing CNA with a fluoroless approach are described. GP mapping and ablation were performed in both atria. From the right atrium (RA), the right atrium-superior vena cava (RA-SVC GP), the posteromedial ganglionated plexus (PMLGP), which can be accessed from the right atrium-coronary sinus ostium, and the Vein of Marshall GP (VOM-GP) were evaluated. From the left atrium (LA), the superior left atrial ganglionated plexus (LSGP), the left inferior ganglionated plexus (LIGP), the right anterior ganglionated plexus (RAGP), and the right inferior ganglionated plexus (RIGP) were targeted. Over the study period, beginning on January 31, 2021, 30 consecutive subjects (15 females/15 males) aged 42.9 ± 13.6years underwent GP ablation. The average subject had 9.5 (± 9.2) episodes of syncope prior to ablation. The average CHADS2-VA2SC score was zero. The average LVEF was 64.8% (± 4.9). Two of the subjects had concomitant ablations, six failed prior medical therapy, and one had a prior pacemaker placed. All of the procedures were done without fluoroscopy. The average follow-up was 604 (± 366) days. There were 8 patients that did not improve symptomatically postfirst ablation. Four of the eight underwent repeat ablation and have subsequently improved. 26/30 patients symptomatically improved after the 1st or 2nd ablation. There were no complications noted. In comparison to the traditional CNA with fluoroscopy, this proof of concept study reveals fluoroless GP ablation can be performed safely. In addition, the durability and success rate are comparable to other studies of CNA. Given the young age of the cohort and the longitudinal risks of ionizing radiation, fluoroless CNA is a feasible procedure for this patient population.

Incidental ablation of ganglionated plexus during atrial fibrillation ablation.

Cardioneuroablation targeting the autonomic nerves within ganglionated plexus (GP) has been used to treat atrial fibrillation (AF). Incidental cardioneuroablation may be an important mechanism by which pulmonary vein isolation (PVI) is effective. Automated fractionation mapping software can identify regions of fractionation correlating with GP locations. To examine the overlap between standard PVI ablation lesions and fractionated electrograms suggestive of GP. We retrospectively examined AF ablations performed from 2021 to 2023 that included only PVI performed using wide antral circumferential isolation without prospective evaluation of fractionation. Retrospectively, a fractionation map was created (width 10 ms, refractory time 30 ms, roving sensitivity 0.1 mv, and threshold of 2). We evaluated the anatomic overlap between PVI lesions and fractionation in regions associated with GP. Among 52 patients (mean 65 (IQR 46-74) years, 82% male, and 69% paroxysmal AF), sites of fractionation corresponding to GP locations were seen in all cases. PVI ablation incidentally overlapped with fractionation in 50 (96%) patients. On average, 26% of the fractionation corresponding with GP locations were incidentally ablated. The highest proportion of fractionated areas were ablated in the left superior (36%) and right superior (31%) GP regions. More complete incidental ablation of these regions was associated with a greater intraprocedural increase in heart rate (ρ = 0.46, p < 0.001), which was subsequently associated with freedom from AF during 15.9 ± 5.2 months of follow-up. Patients undergoing AF ablation universally have fractionated electrograms corresponding to anticipated sites of GP. Partial ablation of these regions frequently occurs incidentally during PVI.

Pain Management of Refractory Hidradenitis Suppurativa: Case Report

Background: Hidradenitis suppurativa (HS) is a chronic, relapsing, and painful inflammatory condition of the skin. Pain in HS is one of the most common symptoms and has a devastating effect on quality of life. Here, we present a unique case of a patient with HS and pain management guidelines used to treat her condition. Case Report: This is a 42-year-old woman with a history of HS, hypertension, depression who presented with one month of pain in her groin crease, vulva, and rectum. She was recently discharged from the hospital for HS superinfection. She was treated with intravenous and oral antibiotics. She previously tried treatment with acetaminophen, lidocaine 2% jelly, gabapentin 400 mg TID, oxycodone, dilaudid, adalimumab, infliximab, topical clindamycin, intralesional steroid injections, and doxycycline. The pain management specialist recommended continuing treatment with gabapentin 400 mg TID and titrate to 600 mg TID as tolerated, and to follow up with the dermatology team to restart infliximab. Discussion: This case demonstrates a complicated, refractory HS condition that necessitates first, second, and third line treatment modalities. Pain control in HS starts by having best control of the underlying disease. The United States and Canadian Hidradenitis Suppurativa Foundations clinical guidelines suggest acute pain management should include topical analgesics (ie, lidocaine), oral acetaminophen, and oral nonsteroidal anti-inflammatory drugs. Chronic pain management should focus on a multidisciplinary approach. Clinical guidelines recommend escalating oral analgesics for pain that doesn’t respond to first-line agents. Opiate use should follow the World Health Organization pain ladder of tramadol, codeine, hydrocodone, and morphine. Neuropathic pain can be treated with pregabalin or gabapentin, titrated as tolerated by patients. Chronic HS lesions can be treated with wide local scalpel, CO2, or electrosurgical excision, and recurrent nodules can be deroofed or excised. Superior hypogastric plexus block and/or ganglion impar block can be considered for refractory cases. Conclusion: HS is an extremely painful condition severely affecting quality of life. Adequate pain management is vital, and a stepwise approach is recommended.

Characteristics of Retinal Vascular Degeneration and the Expression of Vessel-Related Claudin Proteins in Retinal Degeneration Mouse.

This study aimed to investigate the characteristics of retinal vascular degeneration and the expression of vessel-related claudin (CLD) proteins in retinal degeneration mouse (Pde6βrd1/rd1 rd1 mouse). Retinas from wild-type (WT) mice and rd1 mice at postnatal day 3 (P3), P5, P8, P11, P13, P15, P18, and P21 were collected. Immunofluorescence staining was used to assess the retinal vascular plexus, cell proliferation, CLD expression, and retinal ganglion cells (RGCs). The distribution of retinal superficial and deep vessels was determined by isolectin B4 fluorescence staining of retinal flat mounts and frozen sections. Hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated dNTP nick-end labeling were used to investigate retinal histological degeneration and apoptosis in rd1 mice, respectively. Quantitative real-time PCR and Western blot were used to measure the expression of vessel-related CLD-1, -2, -3, and -5, vascular endothelial growth factor A (VEGFA), and vascular endothelial growth factor receptor 2 (VEGFR2) in the retinas. Compared to the WT mice, the rd1 mice displayed delayed but completed progressive development in the retinal superficial vascular plexuses (SVPs) and deep vascular plexuses (DVPs). In the rd1 mice, the thickness of retinal layers gradually decreased and the retinas underwent progressive atrophy and degeneration. The deterioration got worse at the late developmental stage. The declined vessel density of SVP and DVP correlated with the decreased thickness of the full and inner parts of the retina and the reduced number of RGCs. DVP degeneration and the thinning of the outer nuclear layer exhibited an obvious reduction at P15. The expression levels of CLD-1, CLD-2, CLD-3, CLD-5, VEGFA, and VEGFR2 decreased and were consistently lower in the rd1 mice than in WT mice since P15. Rd1 mice exhibited progressive vascular degeneration of retinal SVP and DVP, the thinning and atrophy of retinal ONL and RGC, and the downregulation of vessel-related CLD proteins during the late developmental period. Thus, the rd1 mouse is a useful model of not only retinal neuro-degeneration but also retinal vascular degeneration.

Laser catheter ablation of atrial zones with ganglionated plexi: impact on atrial fibrillation inducibility and the risk of esophageal damage in experimental settings

Aim. To study the potential applicability of transcatheter laser ablation for the destruction of atrial ganglionated plexi (GP) zones and the safety of this technique in relation to inadvertent esophageal damage.Methods. This was a two-stage investigation: (1) ex vivo experiments: the risk of esophageal damage during ablation on the dorsal (posterior) left atrial (LA) wall was assessed; three swine organ complexes were used, which included the heart, lungs and esophagus; (2) in vivo experiments assessing the effects of laser catheter ablation of GP zones on the inducibility of atrial fibrillation (AF) and changes in atrial effective refractory period - included 13 landrace pigs (average weight 38.8±1.2 kg).Ex vivo: laser catheter ablations were performed from the endocardial surface of the LA towards the esophagus with a power of 15 watts of varying duration; ablation was performed under thermal scanning of the LA and esophagus; then a macroscopic examination of the myocardial and esophageal walls was performed.In vivo: before and after catheter laser ablation (15 W) of the GP zones in the right atrium and atrial septum, atrial ERP was assessed with programmed stimulation, and AF induction with high-frequency (33 Hz, 2 min) stimulation was evaluated. At the end of the experiment, the animals were euthanized, and the heart and lungs were collected in a single unit.Results. Ex vivo experiments: in two cases, damage to the endocardium of the LA was detected at an exposure time of 30 s. Damage to the esophagus was observed with a longer exposure time (&gt; 30 seconds) with a 11.3-15.4°C increase in temperature. In the in vivo experiments, 78 laser applications (6±1 in one swine) were delivered to the posterior wall of the right atrium and atrial septum. Atrial effective refractory period was not altered after ablation (183±20 ms vs 186±18 ms, P=0.99). At the baseline, AF was induced in 12 out of 13 animals (92%). After ablation, AF was induced in 7 animals (54%) (P=0.03). There was a trend toward a decrease in the duration of AF after laser ablation of GP zones (18 [5; 141] vs. 2 [0; 14] s after ablation, P=0.06). Transmural damage was observed in 46% of the hearts. No damage to extra-cardiac structures was detected.Conclusion. Ex vivo, laser ablation on the dorsal (posterior) wall of the LA with a power of 15 W and duration &lt;30 s does not lead to visible damage to the esophagus. Laser ablation of atrial GP zones is feasible and reduces the inducibility of AF. No change in atrial effective refractory period is detected following GP zones ablation, when performed from the right atrium.

Anatomic-guided ablation of the right ganglionated plexi validated by the automatic fractionation map

Abstract Background and aim Cardiac autonomic modulation through endocardial ablation of atrial ganglionated plexi (GP) is an alternative strategy in selected patients with severe vagal induced bradyarrhythmias. A strictly anatomical approach targeting the right GPs has demonstrated good success rates but is an empirical approach and has yet to be validated. The presence of fractionated electrograms has been associated with the areas of GPs and can be automatically mapped (fractionation map). The aim of this study was to compare the empirical ablated area, to the automatically assessed area of GPs based on the presence of fractionated electrograms (FEs). Methods We studied eight consecutive patients referred for parasympathetic modulation. A high-density map of the left and right atria (LA, RA) in sinus rhythm was performed. The settings for the automatic map were as follows: bipolar high pass filter of 500 Hz, a fractionation threshold of 4, and a width of 5 ms. The ablation was empirically performed by an operator blinded to the results of the fractionation map, as per site protocol. The ablation was aimed at the anatomic locations of the right GPs in the LA and RA. At the anterior and inferior aspect of the right superior pulmonary vein and inferior aspect of the right inferior pulmonary vein on the LA, and posterior RA opposite to the LA RF applications and around the coronary sinus ostium on the RA (Figure). Before ablation, 2 mg of atropine was administered in bolus, and the increase in heart rate was registered and repeated at the end of the procedure. After the operator completed the ablation, access to the fractionation map was available, and additional radiofrequency (RF) applications were applied as needed (Figure). The number of additional RF applications to cover all the areas with FEs was assessed. Success was defined as an absence of response to atropine after the procedure. Results Three patients underwent autonomic system modulation only, and five underwent additional pulmonary vein isolation (PVI). The mean age was 66 (50-77) years, five males. The median mapping time of the LA and RA was 11 (17-7) and 14 (9-18) min. All patients underwent successful parasympathetic modulation. The initial median (Q1-Q3) increase in heart rate with atropine was 34 (23-39)% versus 0 (0-2)% after ablation, p=0.012. The differences between empiric and FEs map-guided ablation are depicted in the Table. The additional number of points was low. However, a median of 9 (5-15) additional points were added. Conclusions A purely anatomic-guided procedure directed only at the atrial right GPs is usually enough as a therapeutic approach for cardiac autonomic modulation, however, the fractionation map tool helped validate the method and ensure success at the first pass.

Differential and synergistic effects of left and right atrial ablation of paraseptal ganglionated plexuses in a cohort of consecutive patients undergoing cardioneuroablation

Abstract Background Cardioneuroablation (CNA) treats reflex syncope by ablating the main epicardial ganglionated plexuses (GPs) conveying vagal outputs to the sino-atrial (SA) and atrio-ventricular (AV) nodes. The two main GPs, superior paraseptal (SPSGP) and inferior paraseptal (IPSGP), regulate vagal tone to SA and AV nodes, respectively. Both GPs can be targeted with radiofrequency energy (RF) from the right (RA) and left atrium (LA). It is unclear if bi-atrial ablation yields more effective GP ablation or if the ablation sequence affects GP response. Purpose We aimed to assess the added efficacy of ablating the SPSGP and IPSGP in the LA after initial RA ablation, and vice versa, in a separate group of patients. Methods In a consecutive patient population undergoing CNA we evaluated the acute efficacy of RF delivery on the SPSGP and the IPSGP. The population was divided into two consecutive groups: one receiving RF initially in the RA and then in the LA (group 1), and the other in the reverse order (group 2). The acute effect of RF applications was measured as percentage increase in heart rate (HR) for the SPSGP and as reduction of PR interval for the IPSGP. Results Sixty-one patients (50±15 years; 61% males) underwent CNA. Of these, 17 underwent ablation of the SPSGP and IPSGP starting from the RA and completing the procedure in the LA (group 1), while in 44 patients, the procedure was performed in the opposite order (group 2). In group 1, RF delivery on the SPSGP from the RA prompted an increase in HR (54.1±11.1 vs 60.6±14.7 bpm; p=0.03; median HR increment 3.8%, IQR 0-38.3) that was further enhanced after LA ablation (from 57.5±11.9 to 64.5±13.5 bpm; p&amp;lt;0.001; median HR increment: 8.0%, IQR: 2.0-13.5). In group 1, RA ablation of the IPSGP reduced PR interval in a single patient (from 224 to 184 ms), without further shortening after LA ablation. Final CNA success was 82% in group 1. In group 2, RF delivery on the SPSGP from the LA induced a marked increase in HR (58.4±13.1 vs 76.8±16.1 bpm; p&amp;lt;0.001; median HR increase 30.0%, IQR 14.0-43.0). In the same patients, additional ablation from the RA prompted further but lower incremental effect (from 70.0±17.3 to 76.9±17.9 bpm; p&amp;lt;0.001; median HR increment 8.3%, IQR: 0-16.4). In group 2, 4 (9%) patients had PR shortening after LA ablation of the IPSGP (241±93 vs 172±14 ms; p value). Of these, a single patient had further PR reduction after IPSGP RA ablation (from 189 to 161 bpm). Final CNA success was 93% in group 2. Symptoms-free survival was 88% at 16±5 months in group 1 and 89% at 19±7 months in group 2 (p= ns). Conclusions Bi-atrial ablation of the SPSGP and IPSGP provides incremental acute efficacy compared to ablation from either the RA or the LA alone. LA ablation of the main GPs seems an essential component of CNA. The physiological significance of these findings requires further investigationGanglionated Plexuses Segmentation

Cardioneuroablation for vasovagal syncope. Results from an EHRA Survey

Abstract Background Cardioneuroablation (CNA) is a recently introduced catheter-based therapy for vasovagal syncope (VVS), involving the modulation of the cardiac autonomic nervous system. Over the past decade, the body of evidence supporting CNA has consistently grown, sparking increased interest, and leading to broader adoption of this novel therapy for VVS treatment. However, several knowledge gaps persist, particularly concerning clinical indications, methodology, and long-term outcomes. Purpose The aim of this survey is to provide a comprehensive overview of the daily utilization of CNA in Europe. Methods and Results Among 204 participants, half reported that they are already performing CNA in their centres. The survey indicated CNA as an emerging therapy, with most centres initiating this treatment within the last two years. A significant majority of those who responded (71%) adopted a systematic approach by targeting ganglionated plexuses (GPs) in both the right atrium (RA) and left atrium (LA) as their first-line approach. The second most common approach (16%) involved performing ablation LA GPs only in the cases where there is no response following RA ablation. Figure 1 shows the GPs usually targeted for ablation. The most frequent procedural endpoint was the increase in the heart rate. Ninety percent of respondents relied on an anatomical approach for GP localization, while 59% also guided the procedure using electrogram analysis. Less frequently used approaches included pre-procedural imaging (20%), high-frequency stimulation (17%), and spectral analysis (10%). Only 11% of physicians discharged patients who underwent CNA without anticoagulation or antiplatelet therapy. In most cases (58%), respondents discharged their patients with anticoagulation, while 28% on single antiplatelet therapy. Overall, CNA is considered an effective procedure (80% of responders rating its effectiveness at or above 70%) and a safe procedure (with an estimated 1% rate of procedure-related complications, with symptomatic sinus tachycardia being the most frequently reported). Conclusions This survey confirmed high expectations for the future of this therapy, as most responders anticipate that CNA will be indicated as a first-line therapy for patients with recurrent cardioinhibitory VVS. Future efforts are necessary to standardize the procedural flow and peri-procedural patient management.

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.

Predictors of neuromodulation during single-shot thermal atrial fibrillation ablation: a computed tomography imaging analysis

Abstract Background Ganglionated plexi (GPs) are part of the cardiac autonomic nervous system (CANS), which play an important role in the induction and maintenance of atrial fibrillation (AF). Because of the anatomic proximity of the pulmonary veins with GPs, pulmonary vein isolation (PVI) using thermal (radiofrequency (RF) or cryo) ablation, has been shown to concomitantly affect the GPs, as suggested by increased heart rate (HR) after ablation. Right superior pulmonary vein (RSPV) isolation has been reported to have the most evident inhibitory responses to the CANS via modulation of the anterior right ganglionated plexus. Nonetheless, there are also cases with little to no effect on neuromodulation post-ablation. Purpose To assess the clinical and anatomical predictors of thermal ablation-induced CANS changes, as assessed via variations in resting HR post-ablation. Methods We retrospectively analyzed consecutive patients with symptomatic paroxysmal AF who underwent first-time PVI by cryoballoon (CB) or RF balloon (RFB) between January 2022 to November 2022. Patients who were not in sinus rhythm, had cardiac implantable electronic devices, or did not have a contrast-enhanced computed tomography before the ablation were excluded. Pre-ablation and 24-hour post-ablation ECGs in sinus rhythm were collected and analyzed to assess HR. Results A total of 83 patients (CB group, n = 43 vs RFB group, n = 40) were included in the analysis. Baseline patients’ characteristics were similar between the two groups (Table 1). A significant HR increase (ΔHR ≥ 15 bpm) at 24h post-ablation occurred in 31 patients [CB group 16 (52 %), RFB group 15 (48 %)]. Predictors of increased HR were the distance between superior vena cava (SVC) and RSPV (OR 0.51, CI 0.35 - 0.75, p value &amp;lt; 0.01) and age (OR 0.94, CI 0.89 - 0.99, p value &amp;lt; 0.01) (Table 2). Conclusions Single-shot thermal PVI influences the CANS, especially in patients with a shorter SVC - RSPV distance and in younger patients.Table 1Table 2

Heart rate dynamics after pulmonary vein isolation: pulsed-field vs. radiofrequency ablation

Abstract Background The autonomic nervous system (ANS) plays a pivotal role in the onset and maintenance of atrial fibrillation (AF). During thermal ablation, the epicardial ganglionated plexi (GP) can inadvertently be affected, as indicated by a post-ablation increase in heart rate (HR), potentially impacting post-procedural outcomes. Pulsed-field ablation (PFA) offers a safer and potentially more effective alternative, as lesion transmurality is not inversely related to safety as in thermal ablation. However, PFA's tissue selectivity may limit its effectiveness in ablating potential AF triggers like GP. Purpose We aimed to assess the impact of PF and RF energy on GP ablation by examining HR changes following PVI procedures. Methods We examined consecutive paroxysmal AF patients undergoing PVI at a single center, using either a variable-loop circular PFA catheter, as part of the inspIRE trial, or a conventional point-by-point RF catheter (1:2 ratio). ECGs were collected before and after ablation at multiple time points, including 1-hour, 1-day, 1-month, and 3-month intervals, with a 24-hour Holter ECG at 3 months. Patients without obtainable sinus rhythm ECGs at these time points were excluded. We also gathered data on post-ablation antiarrhythmic drug and beta-blocker usage. Data are reported as mean±SD, and analysis employed Student’s t-tests, paired t-tests, chi-squared tests, and multiple linear regression analysis to identify influencing factors. Results A total of 105 patients were included (PF = 35, RF = 70). Baseline demographics were similar (Table A). In the RF group, HR significantly increased at all measured time-points. In contrast, this trend was not observed in the PF group (Figure A and B). Following the procedure, the RF cohort exhibited a significantly higher HR compared to PF (7.3±10.3 vs. 0.8±11 at 1-day, p=0.018), and this difference persisted after 3 months (8.5±10.1 vs. 0.9±9, p&amp;lt;0.001, Figure C). These findings remained consistent when HR was assessed using Holter ECG data (HR at 3 months: mean 72.1±8.8 vs 65.8±9.4, min 55.2 vs 48.9; p=0.002, p=0.001, Figure D). The use of RF energy was the only predictor of HR increase after the ablation procedure (β = 7.687, p &amp;lt; 0.001, Table B). Conclusion Our findings indicates that PFA does not increase resting HR as seen with thermal RF ablation, suggesting limited effect on ANS modulation. The role of adjunctive GP ablation during PVI procedures remains a topic of debate.While PFA shows promising improvement in lesion durability, current evidence does not conclusively establish its advantage over RF. This invites contemplation about whether the addition of GP ablation in RF procedures could be a contributing factor. The absence of HR acceleration may pose issues for patients with sick sinus syndrome or pure vagally mediated AF. Further research is essential to confirm these findings and their clinical implications.Central illustrationTables

Preventing vagal response during pulmonary vein isolation with pulsed field ablation: impact of the order of the targeted pulmonary veins

Abstract Background Vagal responses are frequently observed during pulmonary vein isolation (PVI). Radiofrequency ablation of the anterior right ganglionated plexus (ARGP) before PVI has been demonstrated to effectively prevent VR occurrence. Pulsed-field ablation (PFA) has emerged as an alternative energy source for PVI. Despite PFA being selective for the myocardium, intraprocedural VRs and reversible effects on ganglionated plexi (GP) have been documented during PVI. Purpose We aimed to investigate whether initiating PVI from the right superior pulmonary vein (RSPV) before any other pulmonary veins (PVs) could prevent VR occurrence via concomitant transient ARGP modulation. Methods 60 consecutive paroxysmal atrial fibrillation patients undergoing PVI with the pentaspline PFA ablation catheter were prospectively included. In the first 30 patients, PVI was started from the left superior pulmonary vein (LSPV-first group). In the last 30 patients, the RSPV was targeted first, followed by the left PVs, and finally the right inferior PV (RSPV-first group). VR was defined as sinus bradycardia (&amp;lt;40 beats/min), asystole, or atrioventricular block (AVB). Heart rate (HR) was evaluated at baseline, during PVI, and post-ablation to assess GP modulation. Results Baseline characteristics were similar between the two study groups. VR during PVI occurred in 22 (73%) patients in the LSPV-first group and 3 (10%) in the RSPV-first group (Figure1, p&amp;lt;0.001). A higher rate of VRs was observed in patients in the LSPV-first group compared to patients in the RSPV-first group during ablation of the LSPV and LIPV (73% vs. 7%, p&amp;lt;0.001 and 27% vs. 0%, p=0.005, respectively), while no differences were found during ablation of the right PVs. Temporary pacing was employed in 10 (33%) patients in the LSPV-first group and 3 (10%) in the RSPV-first group (p=0.028). RSPV isolation induced similar acute HR increase in the two groups (13±9 bpm vs 13±10 bpm, p=0.9). However, no significant HR variation was documented in both groups at the end of the procedure compared to baseline (all p&amp;gt;0.05). Conclusion PVI with PFA is frequently associated with intraprocedural VRs when ablation is initiated from the LSPV. However, an RSPV-first approach determined transient HR increase and reduced VR occurrence.Figure 1

Pulmonary vein isolation with additional substrate ablation for atrial fibrillation results in an increased risk for the development of atypical atrial flutter

Abstract Introduction Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) catheter ablation. Several extra pulmonary vein (PV) ablation strategies for substrate modification (PVI plus) have been employed to AF patients. It has not been proven that this approach decreases the recurrence of AF, and it could contribute to increase the risk of developing atypical atrial flutter. Methods Patients submitted to AF catheter ablation at our centre between 2005 and 2020 were included. Using logistic regression, we did a retrospective analysis of the association between the application of PVI plus strategies (such as ablation of the cavo tricuspid isthmus (CTI), ganglion plexus, isolation of the superior vena cava (SVC), mitral isthmus ablation and atrial roof line ablation) and the development of atypical flutter later submitted to ablation. Results Five hundred and seventy-five patients were included (64% males, age 57±12 years [between 14 and 81], 68.2% with paroxysmal AF) with &amp;gt; 1-year follow-up. Five hundred and five (87.8%) had PVI alone. From the 575 patients, 11 (1.9%) developed an atypical flutter during the follow-up, which was later submitted to ablation. The crude ODDS of a patient submitted to a PVI plus strategy developing atypical atrial flutter are 13.92 times higher than the one of those submitted to a stand-alone PVI technique, with a p value &amp;lt;0.001 (95% CI 3.96 – 48.87). When adjusted for age and history of heart failure, the ODDS of a patient submitted to a PVI plus strategy developing atypical atrial flutter are 16.29 times higher than the one of those submitted to a stand-alone PVI technique, with a p value &amp;lt;0.001 (95% CI 3.92 – 67.65). Conclusions Additional substrate ablation for AF significantly increases the risk of developing atypical auricular flutter.Characteristics of the study populationCharacterization of PIV plus strategies

Sinus nodal denervation by targeting the superior paraseptal ganglionated plexus: randomized comparison of right-atrial and bi-atrial cardioneuroablation guided by ablation index

Abstract Background Radiofrequency (RF) catheter ablation of superior paraseptal ganglionic plexus (SPSGP) that significantly suppresses the vagal modulation of the sinus node is used for the treatment of functional bradyarrhythmias. A reasonable effect can be achieved by targeting this plexus from the endocardial aspect of both the right and left atria. Purpose The study aimed to compare the acute efficacy of unifocal right-atrial (RA) and comparably extensive bi-atrial (BA) ablation of SPSGP for sinus nodal denervation as assessed by intraprocedural extracardiac vagus nerve stimulation (ECVS). Methods A population of 22 patients (age: 43±9 years, 55% males) undergoing cardioneuroablation (CAN) for functional bradyarrhythmias were randomized 1:1 to two ablation strategies that included: [1] single RF lesion at the very posterior site of the junction between right atrium and superior vena cava with ablation index (AI) = 800 (RA group) and [2] the same but twice smaller RF lesion (AI = 400) complemented with strictly contralateral left-atrial lesion (AI = 400) at the anterior vestibulum of right superior pulmonary vein (BA group). The effect of ablation was investigated by the post-ablation change in sinus rate and the attenuation of the response of the sinus node to ECVS (frequency: 50 Hz, pulse width: 0.05 ms, output: 1 V/kg [&amp;lt;70V], duration: 5 s) via the right internal jugular vein. Results Per-protocol ablation resulted in sinus acceleration by 9±15 bpm vs. 15±16 bpm (P=0.40) in RA vs. BA groups, respectively. Inducible sinus arrests were shortened by 4.7±4.2 s vs. 6.2±1.5 s (P=0.27) and reached the post-ablation level of 3.0±3.7 s vs. 1.0±0.3 s (P=0.08) in RA vs. BA groups, respectively. The results are also displayed in the Figure as medians, interquartile range (boxes) and total range (whiskers). Complete sinus nodal denervation was achieved in 8/11=73% vs. 11/11=100% patients (Fisher exact test P=0.21) in RA vs. BA groups, respectively. Practically 100% denervation efficacy in the BA group contrasted with 3 patients in the RA group in whom ablation had virtually no effect on ECVS-based indices (duration of post-ablation sinus arrests: 11.2, 8.7, and 5.2 s). Acute effects did not change substantially during the waiting period of 20±5 min. Conclusions In this small study with acute procedural endpoints, unifocal RA ablation of SPSGP appeared numerically less effective for sinus nodal denervation than comparably extensive BA ablation although the difference was formally non-significant. The ECVS-based outcome measure was valuable in detecting the differences between study groups. Change in sinus rate was not a reliable marker of sinus nodal denervation.

Cardioneuroablation for vasovagal syncope: insights on patients' selection, centre settings, procedural workflow and endpoints-results from an European Heart Rhythm Association survey.

Cardioneuroablation (CNA) is a catheter-based intervention for recurrent vasovagal syncope (VVS) that consists in the modulation of the parasympathetic cardiac autonomic nervous system. This survey aims to provide a comprehensive overview of current CNA utilization in Europe. A total of 202 participants from 40 different countries replied to the survey. Half of the respondents have performed a CNA during the last 12 months, reflecting that it is considered a treatment option of a subset of patients. Seventy-one per cent of respondents adopt an approach targeting ganglionated plexuses (GPs) systematically in both the right atrium (RA) and left atrium (LA). The second most common strategy (16%) involves LA GP ablation only after no response following RA ablation. The procedural endpoint is frequently an increase in heart rate. Ganglionated plexus localization predominantly relies on an anatomical approach (90%) and electrogram analysis (59%). Less utilized methods include pre-procedural imaging (20%), high-frequency stimulation (17%), and spectral analysis (10%). Post-CNA, anticoagulation or antiplatelet therapy is prescribed, with only 11% of the respondents discharging patients without such medication. Cardioneuroablation is perceived as effective (80% of respondents) and safe (71% estimated <1% rate of procedure-related complications). Half view CNA emerging as a first-line therapy in the near future. This survey offers a snapshot of the current implementation of CNA in Europe. The results show high expectations for the future of CNA, but important heterogeneity exists regarding indications, procedural workflow, and endpoints of CNA. Ongoing efforts are essential to standardize procedural protocols and peri-procedural patient management.