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

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: 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.

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.

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.

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.

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.

Differential effect of ganglionic plexi ablation in a patient with neurally mediated syncope and intermittent atrioventricular block.

AIMS: In patients with severe neurally mediated syncope (NMS), radiofrequency catheter ablation (RFA) of ganglionic plexi (GP) has been proposed as a new therapeutic approach. Cardio-inhibitory response during NMS is usually related to the sinoatrial (SA) and less frequently to atrioventricular (AV) node. Differential effect of GP ablation on SA and AV node is poorly understood. METHODS AND RESULTS: We report a case of a 35-year-old female with frequent symptomatic episodes of advanced AV block treated by anatomically guided RFA at empirical sites of GPs. After RFA at the septal portion of the right atrium-superior vena cava junction, heart rate accelerated from 62 to 91 beats/min and PR interval prolonged from 213 to 344 ms. Sustained first-degree AV block allowed to observe directly the effects of subsequent RFA on the AV nodal properties. Subsequent RFA at right- and left-sided aspects of the inter-atrial septum had no further effect on heart rate and PR interval. Ablation at the inferior left GP was critical for restoration of normal AV conduction (final PR interval of 187 ms). No bradycardia episodes were observed by implantable loop recorder during the follow-up of 10 months and the patient was symptomatically improved. CONCLUSION: This is the first clinical case showing the differential effect of GP ablation on SA and AV nodal function, and critical importance of targeting the GP at the postero-inferior left atrium. The successful procedure corroborates clinical utility of ablation treatment instead of pacemaker implantation in selected patients with cardio-inhibitory NMS.

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.

Catheter Ablation of Recurrent Paroxysmal Atrial Fibrillation: Is Gap-Closure Combining Ganglionated Plexi Ablation More Effective?

BACKGROUND: For repeat treatment with paroxysmal atrial fibrillation (PAF) recurrence, gap-closure at pulmonary vein ostia alone is not enough. Many recent studies indicated that ganglionated plexi (GPs) denervation could reduce the recurrence of AF. However, it is unclear whether the clinical outcomes of additional GP ablation plus pulmonary veins (PVs ) reisolation during a repeat procedure were associated with less recurrence in PAF patients. The purpose of this study was to evaluate if a repeat procedure of GP ablation (GPA) combining repeated procedure of pulmonary vein isolation (re-PVI), i.e., gap-closure, can offer additional benefit for patients with PAF recurrence. METHOD: A total of 123 consecutive patients with PAF recurrence who underwent success repeat procedures were retrospectively analyzed in our center (2014-2015). Note that 64 patients (group 1, GPA group) were performed with GPA plus re-PVI, while 59 patients (group 2, re-PVI group) had re-PVI (gap-closure) alone. Organized atrial tachycardias (OATs) documented or induced at the end of the procedure were all mapped and ablated. Patients were scheduled for a 12-month follow-up. Clinical presentation and outcome data for the two groups were assessed. RESULT: At the 12-month follow-up 58 of 64 patients (90.6%) in group 1 and 46 of 59 patients (78%) in group 2 remained in sinus rhythm (SR) off antiarrhythmia drugs (AADs) (P = 0.045). CONCLUSION: GPA conferred incremental benefit when performed in addition to re-PVI in patients with PAF recurrence; the GPA group yielded higher success rates than the re-PVI group.

Impact of Anatomically Guided Ganglionated Plexus Ablation on Electrical Firing from Isolated Pulmonary Veins.

BACKGROUND: The mechanisms underlying atrial fibrillation (AF) initiation and pulmonary vein isolation (PVI) effectiveness remain unclear. Ganglionated plexus (GPs) have been implicated in AF initiation and maintenance. In this study, we evaluated the impact of GP ablation in patients with pulmonary vein (PV) firing after PVI. METHODS: Patients with drug-refractory paroxysmal AF undergoing radiofrequency catheter ablation therapy with PVI were screened. Among 840 cases over a 3.75-year period, 12 cases were identified with persistent PV firing (left = 4 and right = 8) after PVI was achieved and left atrial sinus rhythm restored. Adjacent GP ablation was performed anatomically and followed if necessary by additional PV ablation. RESULTS: In eight patients, PV firing was terminated during GP ablation outside of the circumferential ablation line. In one patient, additional PV ablation resulted in cessation of PV firing and in the remaining three patients, firing could not be terminated by GP ablation or additional PVI. CONCLUSION: GP ablation outside of wide antral circumferential line frequently results in the cessation of rapid firing from electrically isolated PVs. These observations suggest that interactions between left atrium and PV beyond electrical conduction warrant consideration in AF mechanisms.

Additional benefit of cryoballoon-based atrial fibrillation ablation beyond pulmonary vein isolation: modification of ganglionated plexi.

AIMS: It has been known that cryoballoon-based pulmonary vein isolation (PVI) is an efficacious and a safe therapeutic option to eliminate triggers of atrial fibrillation (AF). However, the effect of cryoablation on external modifiers of AF-like ganglionated plexi (GP) has never been investigated. In this study, we aimed to investigate whether vagal reactions probably due to GP modification during cryoablation, are associated with success rates during follow-up. METHODS AND RESULTS: A total of 145 patients (age: 54.5 ± 10.1, 52.4% males and 80.7% paroxysmal AF) who were symptomatic despite treatment with ≥ 1 antiarrhythmic drug underwent PVI with cryoballoon. Occurrences of intraprocedural vagal reactions were recorded in all patients. Intraprocedural vagal reaction was observed in 59 patients (40.7%). Vagal reaction characterized by bradycardia and hypotension was more common in patients free of AF recurrence as was the requirement of atropine administration or temporary pacing (46.2 vs. 15.4%, P = 0.004 and 38.7 vs. 7.7%, P = 0.002, respectively). At a median 17 (4-27) months follow-up, AF recurrence was observed in 26 (17.9%) patients. Multivariate Cox regression analysis showed that non-paroxysmal AF, left atrial diameter, and early recurrence significantly increased AF recurrence; however, requirement of atropine administration or temporary pacing (hazard ratio: 0.064; 95% confidence interval: 0.008-0.48, P = 0.008) decreased AF recurrence. CONCLUSION: Our findings indicate that vagal reactions during cryoablation, as a surrogate marker of cardiac ANS modification, decrease AF recurrence in a subgroup of patients with paroxysmal and persistent AF. This finding may be attributed to the concomitant ablation of GP during antral PVI.

Active ganglionated plexi is a predictor of atrial fibrillation recurrence after minimally invasive surgical ablation.

BACKGROUND AND AIM: Ganglionated plexi (GP) ablation has been become an important strategy for treating atrial fibrillation (AF). We hypothesize that active GP is a predictor of AF recurrence after minimally invasive surgical AF ablation. METHODS: Eighty-nine patients with symptomatic lone AF undergoing minimally invasive surgical pulmonary vein isolation combined with GP testing and ablations were followed for a median of 50 months. Success was defined as freedom from any atrial tachyarrhythmia lasting >30 seconds duration. RESULTS: The single-procedure success rate is 56.3% for paroxysmal AF, 27.3% for persistent AF, and 25% for long-term persistent AF. A mean of 4.1 active GPs were identified in each patient. There were more active GP on the right side than on the left side (2.8 ± 2.2 vs. 1.4 ± 1.2, p<0.001). The number of active GP independently predicted recurrence of AF at 12 months (hazard ratios [95% CI]: 0.67 [0.48, 0.95]; p=0.022), 24 months (0.71 [0.53, 0.95]; p=0.019), and 60 months (0.69 [0.54, 0.89]; p=0.004). Patients with active GP above 5 were associated with higher long-term success rates in comparison to patients with less active GP (p=0.014). Duration of AF >24 months, early recurrence of AF, and left atrial diameter also predicted long-term recurrences of AF. CONCLUSIONS: The number of active GP is a predictor of AF recurrence after minimally invasive surgical AF ablation. Patients with more active GP were associated with markedly higher single-procedure success rates.

Ablation of myocardial autonomic ganglion plexus in the treatment of bradyarrhythmia A one-arm interventional study.

OBJECTIVES: To study the complications and effectiveness of the treatment of chronic arrhythmias with cardiac Ganglion Plexus (GP) ablation, and to explore the value of the treatment of chronic arrhythmias with GP ablation. METHODS: This study was a one-arm interventional study of patients from the first hospital of Xinjiang Medical University and the People's Hospital of Xuancheng City admitted (09/2018-08/2021) because of bradyarrhythmia. The left atrium was modeled using the Carto3 mapping system. The ablation endpoint was the absence of a vagal response under anatomically localized and high-frequency stimulation guidance. Postoperative routine follow-up was conducted. Holter data at 3-, 6-, and 12-months were recorded. RESULTS: Fifty patients (25 male, mean age 33.16 ± 7.89 years) were induced vagal response by either LSGP, LIGP, RAGP, or RIGP. The heart rate was stable at 76 bpm, SNRT 1.092s. DC, DR, HR, SDNN, RMSSD values were lower than that before ablation. AC, SSR, TH values were higher than those before ablation, mean heart rate and the slowest heart rate were significantly increased. There were significant differences in follow-up data between the preoperative and postoperative periods (all p < 0.05). All the patients were successfully ablated, and their blood pressure decreased significantly. No complications such as vascular damage, vascular embolism and pericardial effusion occurred. CONCLUSIONS: Left Atrial GP ablation has good long-term clinical results and can be used as a treatment option for patients with bradyarrhythmia.

Pulsed field ablation of the right superior pulmonary vein prevents vagal responses via anterior right ganglionated plexus modulation.

BACKGROUND: Pulsed field ablation (PFA) is selective for the myocardium. However, vagal responses and reversible effects on ganglionated plexi (GP) are observed during pulmonary vein isolation (PVI). Anterior-right GP ablation has been proven to effectively prevent vagal responses during radiofrequency-based PVI. OBJECTIVE: The purpose of this study was to test the hypothesis that PFA-induced transient anterior-right GP modulation when targeting the right superior pulmonary vein (RSPV) before any other pulmonary veins (PVs) may effectively prevent intraprocedural vagal responses. METHODS: Eighty consecutive paroxysmal atrial fibrillation patients undergoing PVI with PFA were prospectively included. In the first 40 patients, PVI was performed first targeting the left superior pulmonary vein (LSPV-first group). In the last 40 patients, RSPV was targeted first, followed by left PVs and right inferior PV (RSPV-first group). Heart rate (HR) and extracardiac vagal stimulation (ECVS) were evaluated at baseline, during PVI, and postablation to assess GP modulation. RESULTS: Vagal responses occurred in 31 patients (78%) in the LSPV-first group and 5 (13%) in the RSPV-first group (P <.001). Temporary pacing was needed in 14 patients (35%) in the LSPV-first group and 3 (8%) in the RSPV-first group (P = .003). RSPV isolation was associated with similar acute HR increase in the 2 groups (13 ± 11 bpm vs 15 ± 12 bpm; P = .3). No significant residual changes in HR or ECVS response were documented in both groups at the end of the procedure compared to baseline (all P >.05). CONCLUSION: PVI with PFA frequently induced vagal responses when initiated from the LSPV. Nevertheless, an RSPV-first approach promoted transient HR increase and reduced vagal response occurrence.

Identification of left atrial ganglionated plexi by dense epicardial mapping as ablation targets for the treatment of concomitant atrial fibrillation.

BACKGROUND: Autonomic ganglionated plexi (GPs) play a significant role in the initiation and maintenance of atrial fibrillation (AF). GPs are key targets for a maze procedure. The purpose of this study was to identify the location of the left atrial GPs based on dense epicardial mapping during a maze procedure in patients with concomitant AF. METHODS: Sixteen patients (age, 68 ± 10 years; 11 males, 69%) with heart failure and concomitant AF (duration 55 ± 86 months) underwent intraoperative epicardial electrophysiological mapping and a GP ablation using the maze procedure at our institution. Twenty-four-site, high-frequency stimulation (1,000/min; output, 18 V; pulse width, 0.75 ms) was performed by placing tweezers directly onto the potential GP sites on the left atrial epicardium. RESULTS: Active GPs were found in 13 (81%) of the 16 patients, and 12 (92%) of 13 patients had active GPs between the right pulmonary veins (PVs) and the interatrial groove. For those patients with active locations, a 7-day event-loop recording demonstrated that 12 (92%) of 13 patients were maintained in sinus rhythm 3 months after the operation. CONCLUSION: Dense epicardial mapping in the potential GP areas identified active GP locations in a high percentage of patients. GPs between the PVs and interatrial groove have a high potential as ablation targets for treatment of concomitant AF.

Regional ganglionated plexus ablation eliminated rapid firing in an electrically isolated pulmonary vein.

Atrial fibrillation (AF) was initiated by rapid firing from left superior pulmonary vein (PV) by administration of isoproterenol (ISP) and adenosine triphosphate (ATP) before ablation. After successful isolation of all PVs, ISP and ATP were administered again. PVs were still isolated but an episode of rapid firing was observed inside the left PV isolation line during sinus rhythm. Radiofrequency energy was then delivered to the areas of superior left ganglionated plexus (GP) and inferior left GP. Then, PV firing could no longer be initiated. It suggests additional GP ablation may have additional benefit to circumferential PV isolation, to reduce the incidence of AF recurrence.

Autonomic denervation with magnetic nanoparticles.

BACKGROUND: prior studies indicated that ablation of the 4 major atrial ganglionated plexi (GP) suppressed atrial fibrillation. METHODS AND RESULTS: superparamagnetic nanoparticles (MNPs) made of Fe(3)O(4) (core), thermoresponsive polymeric hydrogel (shell), and neurotoxic agent (N-isopropylacrylamide monomer [NIPA-M]) were synthesized. In 23 dogs, a right thoracotomy exposed the anterior right GP (ARGP) and inferior right GP (IRGP). The sinus rate and ventricular rate slowing responses to high-frequency stimulation (20 Hz, 0.1 ms) were used as the surrogate for the ARGP and IRGP functions, respectively. In 6 dogs, MNPs carrying 0.4 mg NIPA-M were injected into the ARGP. In 4 other dogs, a cylindrical magnet (2600 G) was placed epicardially on the IRGP. MNPs carrying 0.8 mg NIPA-M were then infused into the circumflex artery supplying the IRGP. The hydrogel shell reliably contracted in vitro at temperatures ≥ 37°C, releasing NIPA-M. MNPs injected into the ARGP suppressed high-frequency stimulation-induced sinus rate slowing response (40 ± 8% at baseline; 21 ± 9% at 2 hours; P=0.006). The lowest voltage of ARGP high-frequency stimulation inducing atrial fibrillation was increased from 5.9 ± 0.8 V (baseline) to 10.2 ± 0.9 V (2 hours; P=0.009). Intracoronary infusion of MNPs suppressed the IRGP but not ARGP function (ventricular rate slowing: 57 ± 8% at baseline, 20 ± 8% at 2 hours; P=0.002; sinus rate slowing: 31 ± 7% at baseline, 33 ± 8 % at 2 hours; P=0.604). Prussian Blue staining revealed MNP aggregates only in the IRGP, not the ARGP. CONCLUSIONS: intravascularly administered MNPs carrying NIPA-M can be magnetically targeted to the IRGP and reduce GP activity presumably by the subsequent release of NIPA-M. This novel targeted drug delivery system can be used intravascularly for targeted autonomic denervation.