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.

A Comparative Review of Vagal Nerve Stimulation Versus Baroreceptor Activation Therapy in Cardiac Diseases.

Sympathetic imbalance coupled with impairment of baroreceptor control is a key factor responsible for hemodynamic abnormalities in congestive heart failure. Vagal nerve stimulation (VNS) and baroreceptor activation therapy (BAT) are two novel interventions for the same. In this paper, we review the role of sympathovagal alterations in cardiac diseases like heart failure, arrhythmia, hypertension (HTN), etc. Studies like neural cardiac therapy for heart failure (NECTAR-HF), autonomic regulation therapy to enhance myocardial function and reduce progression of heart failure (ANTHEM-HF), and baroreflex activation therapy for heart failure (BEAT-HF), which comprise the history, efficacy, limitations, and current protocols, were extensively analyzed in contrast to one another. Vagal nerve stimulation reverses the reflex inhibition of cardiac vagal efferent activity, which is caused as a result of sympathetic overdrive during the course for heart failure. It has shown encouraging results in certain pre-clinical studies; however, there is also a possibility of serious cardiovascular adverse events if given in higher than the recommended dosage. Attenuated baroreflex sensitivity is attributed to cardiac arrhythmogenesis during heart failure. Baroreceptor activation therapy reverses this phenomenon. However, the surgical procedure for baroreceptor stimulation can have unwarranted complications, including worsening heart failure and hypertension. Considering the effectiveness of the given modalities and taking into account the inconclusive evidence of their adverse events, more clinical trials are needed for establishing the future prospects of these interventional approaches.

Generalized Epilepsy With Repetitive Sinus Pauses Following Generalized Tonic-Clonic Seizures Due to Reduced Baroreflex Sensitivity.

Epilepsy and syncope are sometimes difficult to differentiate, and they often occur together. We report here a unique case of severe neuromodulatory syncope associated with generalized epilepsy. A 24-year-old right-handed female with no remarkable history had her first epileptic seizure when she was 15 years old and was diagnosed with epilepsy. However, she had epileptic seizures or fainting spells every few months and was referred to Nara Medical Center at the age of 23 years. No obvious neurological abnormality was present, and no organic abnormality was found on head magnetic resonance imaging. The seizures were symmetrical generalized tonic-clonic seizures (GTCS) without aura, and the patient was unable to stand up for several hours after the seizure. Long-term video electroencephalogram monitoring revealed two types of seizures: (1) GTCS starting with generalized polyspikes and waves and (2) fainting with sinus arrest for up to 10 seconds when the patient tried to stand up after GTCS. After the addition of valproic acid following the diagnosis of generalized epilepsy, her epileptic seizures improved, but syncope remained. We consulted the cardiology department of our hospital and diagnosed mixed neuromodulatory syncope after performing the tilt test. She underwent catheter ablation for cardioneuromodulation, and her syncope improved. Several reports have described reduced baroreflex sensitivity during the interictal period in epilepsy, and seizure-related autonomic dysfunction has been implicated in sudden unexpected death in epilepsy (SUDEP). In addition to suppression of epileptic seizures, when autonomic nervous system symptoms associated with epilepsy are severe, as in this case, a thorough cardiovascular examination should be performed, and the patient should be treated with the goal of preventing SUDEP.

Congenital Central Hypoventilation Syndrome in Israel-Novel Findings from a New National Center.

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare autosomal-dominant disorder of the autonomic nervous system that results from mutations in the PHOX2B gene. A national CCHS center was founded in Israel in 2018. Unique new findings were observed. METHODS: All 27 CCHS patients in Israel were contacted and followed. Novel findings were observed. RESULTS: The prevalence of new CCHS cases was almost twice higher compared to other countries. The most common mutations in our cohort were polyalanine repeat mutations (PARM) 20/25, 20/26, 20/27 (combined = 85% of cases). Two patients showed unique recessive inheritance while their heterozygotes family members were asymptomatic. A right-sided cardio-neuromodulation was performed on an eight-year-old boy for recurrent asystoles by ablating the parasympathetic ganglionated plexi using radiofrequency (RF) energy. Over 36 months' follow-up with an implantable loop-recorder, no bradycardias/pauses events were observed. A cardiac pacemaker was avoided. CONCLUSIONS: A significant benefit and new information arise from a nationwide expert CCHS center for both clinical and basic purposes. The incidence of CCHS in some populations may be increased. Asymptomatic NPARM mutations may be much more common in the general population, leading to an autosomal recessive presentation of CCHS. RF cardio-neuromodulation offers a novel approach to children avoiding the need for permanent pacemaker implantation.

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.

A novel strategy to treat vaso-vagal syncope: Cardiac neuromodulation by cryoballoon pulmonary vein isolation.

BACKGROUND: Clinical management of vaso-vagal syncope (VVS) remains challenging since no therapy has proven to completely prevent VVS recurrence. OBJECTIVE: The purpose of this study was to analyze the mid-term outcome of cryoballoon (CB) cardioneuroablation achieved by pulmonary vein isolation (PVI) in patients with VVS. METHODS: Patients who underwent CB cardioneuroablation in our centers between January 2014 to June 2018 were included. All patients had a history of VVS or pre-syncope despite therapeutic attempts with medical and/or pacing treatments. Patients were excluded in case of structural heart diseases, cerebrovascular diseases or suspected drug-related syncope. Both heart rate (HR) and atrio-ventricular (AV) interval were analyzed on the 12-lead electrocardiogram (ECG) the day before the procedure, the day after, and in the follow-up. RESULTS: In total, 26 patients (76.9% males, 37.5 ± 9.0 years old) were included. All patients underwent a successful procedure with the 28 mm second-generation Arctic Front Advance CB. No major complication occurred. At a mean follow-up of 20.1 ± 11.6 months the freedom from VVS or reflex pre-syncope was 83,7%, with 22 patients free from any clinical recurrence. Basal HR significantly increased the day after the procedure (57.2 bpm vs 78.3 bpm, p < 0.001), while at the final follow-up it stabilized at a value halfway between the 2 previous ones (69.8 bpm, p = 0.0086). The AV interval didn't modify significantly after the procedure. CONCLUSION: Endocardial autonomic denervation achieved by CB PVI appears to be an effective and safe treatment option for patients with refractory VVS and reflex pre-syncope.

Predictors of cardiac neuromodulation achieved by cryoballoon ablation performed in patients with atrial fibrillation who were in sinus rhythm before the ablation.

BACKGROUND: The impact of pulmonary vein isolation (PVI) performed with cryoballoon (CB) on the intrinsic cardiac autonomic nervous system (ICANS) remains unclear. OBJECTIVE: The purpose of this study was to evaluate the predictors and the clinical meaning of cardiac neuromodulation achieved by CB-ablation as assessed by sinus heart rate (HR) response after the procedure. METHODS: Patients who underwent CB-ablation for drug-resistant atrial fibrillation (AF) from January 2014 to October 2018 were included. Twelve­leads rest ECG was taken both before and after the procedure. After discharge, patients were scheduled for follow-up visits at 1, 3, 6, and 12 months and 24 h Holter recordings were obtained at each follow-up visit. All documented AF episodes of >30 s were considered as recurrence. RESULTS: Four-hundred seventy-two patients (62.3% male, age 56.7 ± 13.6 years, 97.2% paroxysmal AF) were included. Mean HR before the procedure was 60.17 ± 10.4 bpm, while the morning after the procedure mean HR was 75.48 ± 12.0 bpm. Age at enrollment (R = -0.26; p < 0.001), baseline HR before the CB-A (R = -0.32; p < 0.001), nadir temperature in each right pulmonary vein (R = -0.11, p = 0.022; R = -0.16; p = 0.001) were significantly associated with the ∆HR. At 2-year follow-up, freedom from recurrences was 83.1% for the patients with HR increase ≥15 bpm after CB-A and 66.3% in patients with HR increase ˂15 bpm (p = 0.021). CONCLUSION: Sinus HR increase is a frequent phenomenon after CB-A, that can be predicted by both clinical and procedural factors and that correlates with better outcome after cryo-PVI.

"Cardio-Neuromodulation" With a Multielectrode Irrigated Catheter: A Potential New Approach for Patients With Cardio-Inhibitory Syncope.

Syncope is frequently neurally mediated and can seriously affect quality of life. Different ablation strategies have been successfully performed. These approaches have not gained wide acceptance and are quite extensive and complex, exposing patients to significant risks. This article reports the case of a 16-year-old girl who was severely affected by frequent and prolonged episodes of syncope and was treated by tailored ablation of the anterior right ganglionated plexus with a multielectrode irrigated catheter. She had fainted >30 times in the 5 years preceding treatment, experiencing approximately 10 severe episodes of syncope in the previous 12 months. After 3 minutes of ablation, the P-P interval was reduced by >400 milliseconds. Syncope disappeared and the patient has remained completely asymptomatic over a follow-up of 22 months. The "reset" basal P-P interval has remained unchanged (follow-up electrocardiogram at 16 months). At 6 months, there was no residual heart rate activity <50 bpm. On 24-hour rhythm registration, P-P intervals ≥1,000 milliseconds (corresponding to a heart rate of ≤60 bpm) were reduced by >16,000 beats. We believe that this case report is original for several reasons: the unusual clinical presentation; the unique structure targeted; the very limited ablation, implying much lower risks for the patient; the anatomical approach; and the different endpoint. This new "cardio-neuromodulation" approach could be useful for the treatment of patients with neurally mediated syncope.