Safety and Efficacy of His Bundle Pacing Validated by Extracardiac Vagal Nerve Stimulation

Study Overview
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Brief Summary
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Different studies for extracardiac vagal nerve stimulation (ECANS) have been published and confirmed the influence of the vagus nerve on automaticity and conduction properties of the sinus node, atria, atrioventricular node, as well as the His-Purkinje system (HPS) and ventricles. However, there are limited data on the clinical value and impact of ECANS as well as vagus nerve activity on the parameters of permanent His-bundle (HB) or left bundle branch (LBB) pacing. Moreover, there have been no prospective studies evaluating the feasibility and efficacy of ECANS and the management of ECANS-induced scenarios, such as an exit block, increase in pacing threshold, as well as vagally mediated arrhythmias and conduction abnormalities in patients with physiological conduction system pacing (HB/LBB pacing). The objective of the HIS-STORY study in humans is to evaluate the clinical value of ECANS in patients with HB/LBB pacing for further development of patient-centered management strategy.

Detailed Description
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This is a multicenter, prospective, open-label, randomized, interventional study enrolling patients with indications for permanent cardiac pacing according to the current European Society of Cardiology Guidelines on Cardiac Pacing. All participants will undergo permanent pacemaker implantation for HB or LBB pacing. Subsequently, an invasive electrophysiological study (EPS) and ECANS will be performed. The 2 x 2 randomisation will be performed, i.e. right vs left side superior ECANS and blinded for operator ultrasonography guided effective vs ineffective inferior vagal nerve stimulation). The randomisation will prove the feasibility and efficacy of superior ECANS and feasibility, efficacy, and reproducibility of ultrasonography guided inferior ECANS. All the measured parameters as well as demographic and clinical data will be recorded in the study database. Patients with an exit block or an increase in a pacing threshold of an HB/LBB electrode will be further managed by electrophysiologists from the research group. The management will be based on clinical assessment and patient's decision and may involve pacemaker reprogramming, pacemaker upgrade with a back-up pacing electrode implantation, or cardio-neuro-ablation.

Official Title
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Safety and Efficacy of HIs Bundle Pacing Validated by electrophySiological STudy, autonOmic Tests and extRacardiac Vagal Nerve Stimulation (HIS-STORY)

Conditions
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Permanent His Bundle Pacing, Permanent Left Bundle Branch Pacing

Intervention / Treatment
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* Diagnostic Test: extracardiac vagal nerve stimulation (ECANS) + EPS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: signed informed consent form effective and stable HB or LBB pacing sinus rhythm during the intervention procedure Exclusion Criteria: contraindications to invasive EPS contraindications to general anesthesia contraindications to atropine administration (e.g., glaucoma) persistent atrial fibrillation or atrial flutter pregnancy diseases that may cause autonomic system neuropathy use of medications that may affect the parasympathetic system a history of cardiac surgery a history of ablation due to arrhythmia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ECANS started from the right vagus nerve<br>superior ECANS and ultrasonography guided inferior ECANS | Diagnostic Test: extracardiac vagal nerve stimulation (ECANS) + EPS<br>* The study intervention will consist of 3 steps, all of which will be performed under general anesthesia: EPS with the measurement of parameters of atrioventricular conduction and programmed atrial and ventricular pacing. ECANS of the right and the left vagus nerve (from the right and left internal jugular vein, respectively; patients will be randomized to start from the right or the left side) performed during: 1) the patient's spontaneous heart rhythm (if present); 2) HB/LBB pacing with permanently programmed impulse parameters; 3) HB/LBB pacing at a pacing threshold of +0.1 V; and 4) 5 minutes after intravenous injection of atropine (0.02-0.04 mg/kg). EPS with the measurement of parameters of atrioventricular conduction and programmed atrial and ventricular pacing.<br>|
| Active Comparator: ECANS started from the left vagus nerve<br>superior ECANS and ultrasonography guided inferior ECANS | Diagnostic Test: extracardiac vagal nerve stimulation (ECANS) + EPS<br>* The study intervention will consist of 3 steps, all of which will be performed under general anesthesia: EPS with the measurement of parameters of atrioventricular conduction and programmed atrial and ventricular pacing. ECANS of the right and the left vagus nerve (from the right and left internal jugular vein, respectively; patients will be randomized to start from the right or the left side) performed during: 1) the patient's spontaneous heart rhythm (if present); 2) HB/LBB pacing with permanently programmed impulse parameters; 3) HB/LBB pacing at a pacing threshold of +0.1 V; and 4) 5 minutes after intravenous injection of atropine (0.02-0.04 mg/kg). EPS with the measurement of parameters of atrioventricular conduction and programmed atrial and ventricular pacing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Loss of HB/LBB capture or significant increase in pacing threshold | significant increase in pacing threshold = above the permanently programmed impulse amplitude of HB/LBB electrode induced by ECANS | 0-12 months after HB/LBB pacemaker implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A nonsignificant increase in pacing threshold | below the permanently programmed impulse amplitude of HB/LBB electrode induced by ECANS | 0-12 months after HB/LBB pacemaker implantation | 
| Prolongation of the stimulus-QRS interval during HB/LBB pacing induced by ECANS |  | 0-12 months after HB/LBB pacemaker implantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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His bundle pacing, left bundle branch pacing, extracardiac vagal nerve stimulation