Cardiac Autonomic Denervation for Cardio-inhibitory Syncope

Study Overview
=================
Brief Summary
-----------------
Background: Autonomic system modification is an established therapeutic approach that has been increasingly used for the treatment of vagal-related symptomatic bradycardia, such as cardio-inhibitory vasovagal syncope1-12. Although convincing results had been reported from small populations, a large randomized study providing robust evidence on the efficacy of this approach has not yet been performed. Hypothesis: Cardiac autonomic system modification is effective for the treatment of vagal-related symptomatic bradycardia, and is associated better clinical results as compared to placebo.

Official Title
-----------------
Cardiac Autonomic Denervation for Cardio-inhibitory Syncope

Conditions
-----------------
Bradycardia; Syncope, Syncope, Vasovagal

Intervention / Treatment
-----------------
* Procedure: Electrophysiological study
* Procedure: Electrophysiological study and Right side Ganglionated Plexi ablation
* Procedure: Electrophysiological study and bi-atrial Ganglionated Plexi ablation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged between 18 and 70 years old. Cardio-inhibitory response (VASIS 2A or 2B) during tilt test, or after carotid sinus massage. Patients with bradycardia mediated by vagal hypertonia documented on 24-hour Holter monitoring and a clear relationship with symptoms. Exclusion Criteria: Ages under 18 and over 70 Presence of structural heart disease documented by echocardiography. Hypothyroidism and hyperthyroidism, drug effects, obstructive sleep apnea and other causes of secondary bradycardia. Anatomical disease of the conduction system.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized, prospective, sham controll, on a 1:1:1 basis to group A (Sham - 15 patients); group B (right sided denervation - 15 patients); and group C (bilateral denervation - 15 patients)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Group A<br>A diagnostic electrophysiological study will be performed in patients of group A | Procedure: Electrophysiological study<br>* Electrophysiological study: patients in a fasting state and under total intravenous anesthesia Intracardiacelectrogramsare displayed simultaneously on a multichannel recorder. Programmed atrial and ventricular stimulation are performed to rule out sustained arrhythmias, primary conduction system dysfunction, and sick sinus syndrome.<br>|
| Active Comparator: Group B<br>A electrophysiological study with cardiac denervation, with right Ganglionated Plexi ablation exclusively will be performed in patients of group B | Procedure: Electrophysiological study and Right side Ganglionated Plexi ablation<br>* Electrophysiological study: patients in a fasting state and under total intravenous anesthesia Intracardiacelectrogramsare displayed simultaneously on a multichannel recorder. Programmed atrial and ventricular stimulation are performed to rule out sustained arrhythmias, primary conduction system dysfunction, and sick sinus syndrome. GP Mapping and Cardiac denervation: Specific atrium sites are empirically identified as GP by presumed anatomic location based on previous works (anatomic mapping): In the RA: the posterior aspect of the interatrial septum, between the posterior wall and coronary sinus ostium; and, the septal aspect of the superior vena cava junction (opposite to the LA GP tags). A 3.5-mm irrigated tip catheter will be used to deliver radiofrequency energy (50°C, 20-30 W, for 30-60 seconds) with a 17 mL/min irrigation flow.<br>|
| Active Comparator: Group C<br>A electrophysiological study with cardiac denervation, with right and left Ganglionated Plexi ablation will be performed in patients of group C. | Procedure: Electrophysiological study and bi-atrial Ganglionated Plexi ablation<br>* Electrophysiological study: patients in a fasting state and under total intravenous anesthesia Intracardiacelectrogramsare displayed simultaneously on a multichannel recorder. Programmed atrial and ventricular stimulation are performed to rule out sustained arrhythmias, primary conduction system dysfunction, and sick sinus syndrome. GP Mapping and Cardiac denervation: Specific atrium sites are empirically identified as GP by presumed anatomic location based on previous works(anatomic mapping): In the LA: the inferior right GP (septal aspect of the right pulmonary veins [PV]) antra, and LA posterior wall. In the RA: the posterior aspect of the interatrial septum, between the posterior wall and coronary sinus ostium; and the septal aspect of the superior vena cava junction (opposite to the LA GP tags). A 3.5-mm irrigated tip catheter will be used to deliver radiofrequency energy (50°C, 20-30 W, for 30-60 seconds) with a 17 mL/min irrigation flow.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| recurrence of syncope | To compare the recurrence of syncope or pre-syncope and a negative tilt test with the different techniques of electrophysiological procedures currently used. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| electrocardiographic and electrophysiological parameters | Compare the following electrocardiographic and electrophysiological parameters of vagal attenuation: Heart rate (bpm - beats per minute); Internal AH (represents AV internodal conduction time, with normal values between 50-120 ms); Wenckebach cycle; Presence of Holter pauses 30 days after the intervention. | 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cardiac denervation, Cardio-inhibitory syncope