Cardioneuroablation for pediatric patients with functional sinus node dysfunction and paroxysmal atrioventricular block.

INTRODUCTION: Severe transitory episodes of bradycardia with subsequent syncope in children are common, and generally portend a benign prognosis. Rarely, patients may experience prolonged asystolic episodes secondary to significant sinus pauses (SP) or paroxysmal atrioventricular block (AVB). Cardioneuroablation (CNA) is a catheter-based intervention, used to identify and ablate the epicardial ganglionated plexi (GP), which results in disruption of the vagal-mediated parasympathetic input to the sinus and atrioventricular node. OBJECTIVE: Describe the methodology and role of CNA for treatment of pediatric patients with functional AVB or SP. METHODS: This is a single-center, case series study. Patients with SP or AVB, 21 years of age or younger, who underwent CNA between 2015 and 2021 were included. CNA was performed via anatomically guided and high-frequency stimulation methods. RESULTS: Six patients were included. The median age was 18.9 years (range 12.3-20.9 years), 33% female. Two patients had prolonged SP, two had paroxysmal AVB, and two had both SP and AVB. Four patients had prior syncope. The median longest pause was 8.9 s (range 3.9-16.8) with 11 total documented pauses (range 2-231) during the 6 months pre-CNA. Post-CNA, the median longest pause was 1.3 s (range 0.8-2.2) with one documented SP after termination of atrial tachycardia at the 3-month follow-up. At 6 months, the median longest pause was 1.1 s (0.8-1.3) with 0 documented pauses. No patients had syncope post-CNA. CONCLUSION: CNA may be an effective alternative to pacemaker implantation in pediatric patients with syncope or significant symptoms secondary to functional SP or AVB.

Long-term outcomes of cardioneuroablation with and without extra-cardiac vagal stimulation confirmation in severe cardioinhibitory neurocardiogenic syncope.

BACKGROUND: Cardioneuroablation (CNA) is a novel therapeutic approach for functional bradyarrhythmias, specifically neurocardiogenic syncope or atrial fibrillation, achieved through endocardial radiofrequency catheter ablation of vagal innervation, obviating the need for pacemaker implantation. Originating in the nineties, the first series of CNA procedures was published in 2005. Extra-cardiac vagal stimulation (ECVS) is employed as a direct method for stepwise denervation control during CNA. OBJECTIVE: This study aimed to compare the long-term follow-up outcomes of patients with severe cardioinhibitory syncope undergoing CNA with and without denervation confirmation via ECVS. METHOD: A cohort of 48 patients, predominantly female (56.3%), suffering from recurrent syncope (5.1 ± 2.5 episodes annually) that remained unresponsive to clinical and pharmacological interventions, underwent CNA, divided into two groups: ECVS and NoECVS, consisting of 34 and 14 cases, respectively. ECVS procedures were conducted with and without atrial pacing. RESULTS: Demographic characteristics, left atrial size, and ejection fraction displayed no statistically significant differences between the groups. Follow-up duration was comparable, with 29.1 ± 15 months for the ECVS group and 31.9 ± 20 months for the NoECVS group (p = .24). Notably, syncope recurrence was significantly lower in the ECVS group (two cases vs. four cases, Log Rank p = .04). Moreover, the Hazard ratio revealed a fivefold higher risk of syncope recurrence in the NoECVS group. CONCLUSION: This study demonstrates that concluding CNA with denervation confirmation via ECVS yields a higher success rate and a substantially reduced risk of syncope recurrence compared to procedures without ECVS confirmation.

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.

Making certain that noninvasive therapy for vasovagal syncope has failed before proceeding to invasive interventions.

There is a perceived need to express concisely the advice of guidelines in the context of consideration of invasive management of highly symptomatic vasovagal syncope. In response to this need the table is presented as a checklist and the text adds explanation and details. It is anticipated that this will prove to be of value for clinicians.

Mechanism-based therapy of non-cardiac syncope: a practical guide.

The term non-cardiac syncope includes all forms of syncope, in which primary intrinsic cardiac mechanism and non-syncopal transient loss of consciousness can be ruled out. Reflex syncope and orthostatic hypotension are the most frequent aetiologies of non-cardiac syncope. As no specific therapy is effective for all types of non-cardiac syncope, identifying the underlying haemodynamic mechanism is the essential prerequisite for an effective personalized therapy and prevention of syncope recurrences. Indeed, choice of appropriate therapy and its efficacy are largely determined by the syncope mechanism rather than its aetiology and clinical presentation. The two main haemodynamic phenomena leading to non-cardiac syncope include either profound hypotension or extrinsic asystole/pronounced bradycardia, corresponding to two different haemodynamic syncope phenotypes, the hypotensive and bradycardic phenotypes. The choice of therapy-aimed at counteracting hypotension or bradycardia-depends on the given phenotype. Discontinuation of blood pressure-lowering drugs, elastic garments, and blood pressure-elevating agents such as fludrocortisone and midodrine are the most effective therapies in patients with hypotensive phenotype. Cardiac pacing, cardioneuroablation, and drugs preventing bradycardia such as theophylline are the most effective therapies in patients with bradycardic phenotype of extrinsic cause.

Cardioneuroablation for treatment of carotid sinus syndrome secondary to oropharyngeal squamous cell cancer.

Head and neck tumors can rarely cause carotid sinus syndrome and this often resolves by surgical intervention or palliative chemoradiotherapy. If these modalities are not an option or are ineffective, the most preferred treatment is permanent pacemaker therapy. Here, we present the first case of cardioneuroablation treatment performed in patient with oropharyngeal squamous cell cancer who developed recurrent asystole and syncope attacks due to compression of the carotid sinus on neck movement.

Ganglionated plexi ablation in the right atrium for the treatment of cardioinhibitory syncope.

Neurocardiogenic syncope, also called vasovagal syncope, represents one of the clinical manifestations of neurally mediated syncopal syndrome. Generally, the prognosis of the cardioinhibitory form of neurocardiogenic syncope is good, but quality of life is seriously compromised in patients who experience severe forms. Drug therapy has not achieved good clinical results and very heterogeneous data come from studies regarding permanent cardiac pacing. In this scenario, the ganglionated plexi ablation has been proposed as an effective and safe method in patients with cardioinhibitory neurocardiogenic syncope, especially in young patients in order to avoid or prolong, as much as possible, the timing of definitive cardiac pacing. Certainly, making this procedure less extensive and limiting the ablation in the right atrium (avoiding the potential complications of a left atrial approach) and at level of anatomical regions of the most important ganglionated plexy, considered 'gateway' of the sino-atrial and atrio-ventricular node function (through the recognition of specific endocardial potentials), could be very advantageous in this clinical scenario. Finally, randomized, multicentre, clinical trials on a large population are needed to better understand which is the best ablation treatment (right-only or bi-atrial) and provide evidence for syncope guidelines.

Cardioneuroablation for the Treatment of Vasovagal Syncope: Current Status and Impact on Quality of Life.

PURPOSE OF REVIEW: Vasovagal syncope (VVS) is a common entity causing transient loss of consciousness and affecting quality of life. Guideline-recommended therapy involves conservative measures and pacing in selected patients. Cardioneuroablation (CNA) targeting the ganglionated plexi in the heart has been shown to reduce excessive vagal excitation, which plays a major role in the pathophysiology of VVS and functional bradycardia. RECENT FINDINGS: The introduction of CNA has fueled research into its value for the treatment of VVS. Multiple observational studies and one randomized trial have demonstrated the safety and efficacy of CNA and the positive impact on quality of life. This review describes the rationale and CNA procedural techniques and outcomes. Patient selection and future directions have also been described. Cardioneuroablation is a promising treatment for patients with recurrent VVS and functional bradycardia. Further large-scale randomized studies are needed to further verify the safety and efficacy of this approach.

Ganglionated Plexus Ablation Procedures to Treat Vasovagal Syncope.

Vasovagal syncope (VVS) refers to a heterogeneous group of conditions whereby the cardiovascular reflexes normally controlling the circulation are interrupted irregularly in response to a trigger, resulting in vasodilation, bradycardia, or both. VVS affects one-third of the population at least once in their lifetime or by the age of 60, reduces the quality of life, and may cause disability affecting certain routines. It poses a considerable economic burden on society, and, despite its prevalence, there is currently no proven pharmacological treatment for preventing VVS. The novel procedure of ganglionated plexus (GP) ablation has emerged rapidly in the past two decades, and has been proven successful in treating syncope. Several parameters influence the success rate of GP ablation, including specific ablation sites, localization and surgical techniques, method of access, and the integration of other interventions. This review aims to provide an overview of the existing literature on the physiological aspects and clinical effectiveness of GP ablation in the treatment of VVS. Specifically, we explore the association between GPs and VVS and examine the impact of GP ablation procedures as reported in human clinical trials. Our objective is to shed light on the therapeutic significance of GP ablation in eliminating VVS and restoring normal sinus rhythm, particularly among young adults affected by this condition.

Pericarditis following left atrial ablation.

INTRODUCTION: We aimed to evaluate the incidence of acute pericarditis following cardioneuroablation (CNA) and to compare this with patients undergoing left atrial (LA) radiofrequency ablation for atrial fibrillation (AF). METHODS AND RESULTS: This is a single-center prospective study. During the study period, CNA for vasovagal syncope was performed in 42 patients, pulmonary vein isolation (PVI) for paroxysmal AF in 46 patients, and posterior wall isolation (PWI) in addition to PVI for persistent AF in 22 patients. Pericarditis was reported by 18 (16.4%) patients overall: 1 (2.4%) patient in CNA group, 8 (17.4%) patients in PVI group, and 9 (40.9%) patients in PWI (p < .001). On univariable logistic regression analysis, CNA was associated with a lower risk of pericarditis (odds ratio 0.11, 95% confidence interval [CI] 0.01-0.97), while ablation of PWI plus PVI was associated with a higher risk of pericarditis compared with PVI (odds ratio 3.29, 95% CI 1.05-10.3). CONCLUSION: This study shows that pericarditis is extremely uncommon following CNA and is significantly less frequent than following AF ablation. This difference is likely related to the much lower amount of LA ablation necessary in this group.

Procedural and short-term results of electroanatomic-mapping-guided ganglionated plexus ablation by first-time operators: A multicenter study.

INTRODUCTION: Single-center observational studies have shown promising results with fragmented electrogram (FE)-guided ganglionated plexus (GP) ablation in patients with vagally mediated bradyarrhythmia (VMB). We aimed to compare the acute procedural characteristics during FE-guided GP ablation in patients with VMB performed by first-time operators and those of a single high-volume operator. METHODS AND RESULTS: This international multicenter cohort study included data collected over 2 years from 16 cardiac hospitals. The primary operators were classified according to their prior GP ablation experience: a single high-volume operator who had performed > 50 GP ablation procedures (Group 1), and operators performing their first GP ablation cases (Group 2). Acute procedural characteristics and syncope recurrence were compared between groups. Forty-seven consecutive patients with VMB who underwent FE-guided GP ablation were enrolled, n = 31 in Group 1 and n = 16 in Group 2. The mean number of ablation points in each GP was comparable between groups. The ratio of positive vagal response during ablation on the left superior GP was higher in Group 1 (90.3% vs. 62.5%, p = .022). Ablation of the right superior GP increased heart rate acutely without any vagal response in 45 (95.7%) cases. The procedure time was longer in group 2 (83.4 ± 21 vs. 118.0 ± 21 min, respectively, p < .001). Over a mean follow-up duration of 8.0 ± 3 months (range 2-24 months), none of the patients suffered from syncope. CONCLUSION: This multi-center pilot study shows for the first time the feasibility of FE-guided GP ablation across a large group of procedure-naïve operators.

QTc shortening effect of ganglionated plexi ablation.

BACKGROUND: 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). AIMS: To compare the effects of GPA (group 1) to pulmonary vein isolation + GPA (group 2) on QTc. MATERIAL AND METHODS: 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. RESULTS: 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. DISCUSSION: 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 for cardioinhibitory vasovagal syncope.

BACKGROUND: Cardioneuroablation (CNA) is an emerging technique being used to treat patients with cardioinhibitory vasovagal syncope (VVS). We describe a case of CNA in targeting atrial ganglionated plexi (GP) based upon anatomical landmarks and fractionated electrogram (EGM) localization in a patient with cardioinhibitory syncope. CASE PRESENTATION: A 20-year-old healthy female presented with malignant VVS and symptomatic sinus pauses, with the longest detected at 10 s. She underwent acutely successful CNA with demonstration of vagal response (VR) noted after ablation of left sided GP, and tachycardia noted with right sided GP ablation. All GP sites were defined by anatomical landmarks and EGM analysis. By using the fractionation mapping software of Ensite Precision mapping system with high density mapping, fragmented EGMs were successfully detected in each GP site. One month after vagal denervation, there were no recurrent syncopal episodes or sinus pauses. Longer term follow-up with implantable loop recorder is planned. CONCLUSION: We performed CNA in a patient with VVS by utilizing a novel approach of combined use of high density mapping and fractionation mapping software. With this approach, we were able to detect fractionation in all GP sites and demonstrate acute VR. This workflow may allow for a new, standardized technique suitable for widespread use.

Management strategies for vasovagal syncope.

Vasovagal syncope (VVS) (or neurocardiogenic syncope) is a common clinical condition that is challenging to both physicians and patients alike. Severe episodes of recurrent syncope can result in physical injury as well as psychological distress. This article provides a brief overview of current management strategies and a detailed overview of therapeutic modalities such as closed loop stimulation (CLS) and cardioneuroablation (CNA).

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.

Effects of permanent cardiac pacing on ventricular repolarization when compared to cardioneuroablation.

INTRODUCTION: The impact of cardioneuroablation (CNA) on ventricular repolarization by using corrected QT interval (QTc) measurements has been recently demonstrated. The effects of cardiac pacing (CP) on ventricular repolarization have not been studied in patients with vasovagal syncope (VVS). We sought to compare ventricular repolarization effects of CNA (group 1) with CP (group 2) in patients with VVS. METHODS: We enrolled 69 patients with age 38 ± 13 years (53.6% male), n = 47 in group 1 and n = 22 in group 2. Clinical diagnosis of cardioinhibitory type was supported by cardiac monitoring or tilt testing. QTc was calculated at baseline (time-1), at 24 h after ablation (time-2), and at 9-12 months (time-3) in the follow-up. RESULTS: In the group 1, from time-1 to time-2, a significant shortening in QTcFredericia (from 403 ± 27 to 382 ± 27 ms, p < 0.0001), QTcFramingham (from 402 ± 27 to 384 ± 27 ms, p < 0.0001), and QTcHodges (from 405 ± 26 to 388 ± 24 ms, p < 0.0001) was observed which remained lower than baseline in time-3 (373 ± 29, 376 ± 27, and 378 ± 27 ms, respectively). Although the difference between measurements in time-1 and time-2 was not statistically significant for QTcBazett, a significant shortening was detected between time-1 and time-3 (from 408 ± 30 to 394 ± 33, p = 0.005). In the group 2, there was no time-based changes on QTc measurements. In the linear mixed model analysis, the longitudinal reduction tendency in the QTcFredericia and QTcFramingham was more pronounced in group 1. CONCLUSIONS: Our results demonstrate that CNA reduces QTc levels through neuromodulation effect whereas CP has no effect on ventricular repolarization in patients with VVS.

Permanent pacing for recurrent vasovagal syncope: New answers or just more questions?

Vasovagal syncope (VVS) is a clinical condition related to bradycardia (cardioinhibitory response) and/or hypotension (vasodepressor response), likely mediated by parasympathetic overactivity and sympathetic withdrawal. Although clinical presentation is usually related to a self-limited event, frequent episodes or events without prodrome might be debilitating. There are limited medical therapies proven effective in randomized clinical trials. In patients not responsive to standard therapy, permanent pacemaker therapy may be suggested. However, the role of cardiac pacing for the prevention of syncope recurrences remains controversial due to difficulties to exclude potential role of the vasodepressor component during the episode.

Anatomic guided ablation of the atrial right ganglionated plexi is enough for cardiac autonomic modulation in patients with significant bradyarrhythmias.

INTRODUCTION: Cardiac autonomic system modulation by endocardial ablation targeting atrial ganglionated plexi (GP) is an alternative strategy in selected patients with severe functional bradyarrhythmias, although no consensus exists on the best ablation strategy. The aim of this study was to evaluate if a simplified approach by a purely anatomical guided ablation of just the atrial right GP is enough for the treatment of these patients. METHODS: We prospectively enrolled patients with significant functional bradyarrhythmias and performed endocardial ablation purely guided by 3D electroanatomic mapping directed at the atrial right GP and accessed parameters of parasympathetic modulation and recurrence of bradyarrhythmias. RESULTS: Thirteen patients enrolled (76.9% male, median age 51, 42-63 years). After ablation, a median RR interval shortening of 28.3 (25.6-40.3)% occurred (1111, 937.5-1395.4 ms to 722.9, 652.2-882.4 ms, p = 0.0002). The AH interval also shortened (19, 10.5-35.7%) significantly after the procedure (115, 105-122 ms to 85, 71-105 ms, p = 0.0023) as well as Wenckebach cycle length (11.1, 5.9-17.8% shortening) from 450, 440-510 ms to 430, 400-460 ms, p = 0.0127. On 24-h Holter monitoring there was significant increase in heart rates (HR) of patients after ablation (minimal HR increased from 34 (26-43)bpm to 49 (43-56)bpm, p = 0,0102 and mean HR from 65 (47-72)bpm to 78 (67-87)bpm, p = 0.0004). No patients had recurrence of symptoms or significant bradyarrhythmias during a median follow-up of 8.4 months. CONCLUSIONS: A purely anatomic guided procedure directed only at the atrial right ganglionated plexi seems to be enough as a therapeutic approach for cardioneuroablation in selected patients with significant functional bradyarrhythmias.

Ultrasound-guided imaging for vagus nerve stimulation to facilitate cardioneuroablation for the treatment of functional advanced atrioventricular block.

We present a case study article demonstrating successful implementation of ultrasound guided extra cardiac vagus nerve stimulation during cardioneuroablation. To our knowledge it is first published description of this technique, as most ECVS are done in the internal jugular vein bulb area. This method allows for reduction of fluoroscopy time, and most importantly reproducible vagus nerve capture especially after full bi-nodal (sinus and atrioventricular) cardioneuroablation when stimulation of vagus nerve may not give any effect in the heart. This article includes a case study with "dual component" atrioventricular block, where functional component is cured with cardioneuroablation, but structural (PR elongation) remains after procedure.

[Ablation of ganglionated plexi to treat symptomatic parasympathetic induced atrioventricular block].

According to clinical guidelines a symptomatic atrioventricular block (AV block) is treated with a pacemaker. For young individuals such a therapy can be difficult due to possible long term complications such as infections, lead disruptions and pacemaker induced cardiomyopathy. We describe a twenty year old man with recurrent syncopes due to intermittent parasympathetic caused AV block of grade 2. The patient underwent cardioneuroablation where parasympathetic ganglia in the right atrium were ablated. After the procedure the PR interval normalized. This procedure has never been performed in Iceland before and there is a limited amount of case reports in the literature.