Impact of Atrio-ventricular Optimization With His Bundle Pacing on Treatment of Atrio-ventricular Dromotropathy

Study Overview
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Brief Summary
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This study aims to determine the clinical and hemodynamic benefit of atrio-ventricular (AV) resynchronization with His bundle pacing in patients with symptomatic first degree AV block.

Detailed Description
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The term AV dyssynchrony was introduced by Salden F. and coauthors in 2018. It stands for the adverse effects of AV dyssynchrony due to PR interval prolongation. According to the ESC and ACC guidelines, severe first degree AV block is an IIa indication for permanent pacemaker implantation, yet data on these patients' clinical outcomes are scarce. To independently determine the impact of AV resynchronization, His bundle pacing will be used to avoid intraventricular desynchronization. Symptomatic patients with severe first-degree AV block and echocardiographically proven AV dyssynchrony will be included in the study. All patients will receive a dual-chamber pacemaker with an atrial lead positioned in the right atrium and ventricular lead placed on the bundle of His. In a single-blind cross-over design, patients will be randomized to AV sequential His bundle pacing with echo-guided AV optimization or back-up VVI pacing mode. Each study period will last for three months. At the end of both periods, cardiopulmonary exercise testing, complete echocardiographic study, and clinical evaluation will be performed. Peak oxygen uptake and echocardiography-based hemodynamic parameters in both periods will be compared.

Official Title
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Impact of Atrio-ventricular Optimization With His Bundle Pacing on Treatment of Atrio-ventricular Dromotropathy

Conditions
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Atrioventricular Block, Atrioventricular Dyssynchrony

Intervention / Treatment
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* Device: His bundle pacing, AV optimized
* Device: Backup VVI pacing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First OR second degree Mobitz type 1 atrioventricular block with a PR interval > 250 ms left ventricular ejection fraction > 50% echocardiographic criteria of atrioventricular dyssynchrony (diastolic filling time/RR interval ratio < 0,4 OR fusion of E and A waves OR diastolic mitral regurgitation) symptoms on exertion (dyspnea, palpitations) insufficient shortening of PR interval during exercise (PR interval > 200 ms at heart rate of 100 beats per minute) Exclusion Criteria: left ventricular ejection fraction < 50% third degree atrioventricular block atrial fibrillation sinus node disease left bundle branch block right bundle branch block ventricular arrhythmia that indicates implantation of cardioverter defibrillator consumption of drugs that influence atrioventricular conduction active bacterial infection inability to undergo cardiopulmonary exercise test anaemia (haemoglobin concentration < 100 g/L) pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: His bundle pacing, AV optimized<br>Pacemaker programmed to DDD mode with ventricular lead placed on the bundle of His and echocardiographically optimized AV delay. | Device: His bundle pacing, AV optimized<br>* A Select Secure 3830 (Medtronic, MN, USA) pacing lead will be placed on the bundle of His. In case of unsuccessful His capture, left bundle branch area pacing is going to be targeted. Pacemaker will be programmed to a low base rate and a high tracking rate to allow for intrinsic sinus rhythm. AV delay will be optimized with echocardiography to the shortest AV delay without truncation of the A wave on transmitral pulse wave doppler.<br>|
| Sham Comparator: Backup VVI pacing<br>Pacemaker programmed to ventricular only pacing with low base rate (40/min) to allow intrinsic rhythm. | Device: Backup VVI pacing<br>* Pacemaker will be programmed to VVI (ventricular only) mode with low base rate as to allow for intrinsic sinus rhythm without AV optimization.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in exercise capacity | Measured by peak oxygen consumption on cardiopulmonary exercise test | Baseline, 3 months, 6 months | 
| Changes in left ventricular stroke volume | Measured by echocardiography | Baseline, 3 months, 6 months | 
| Changes in quality of life using the 5 level EQ-5D questionnaire | EQ-5D is a standardized measure of health status consisting of 2 pages - the EQ-5D descriptive system (descriptive system with five levels) and the EQ visual analog scale ranging from 0 (worst state) to 100 (best state). | Baseline, 3 months, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in left ventricular volume | End diastolic volume measured echocardiographicaly with biplane Simpson method | Baseline, 3 months, 6 months | 
| Changes in left atrial volume | Left atrial volume indexed by body surface area measured by echocardiography | Baseline, 3 months, 6 months | 
| Changes in the measure of left ventricular mechanical dyssynchrony | Measured by mid-ventricular radial speckle-tracking strain with an anteroseptal to posterior wall delay (AS-P delay) | Baseline, 3 months, 6 months | 
| Changes in QRS complex width | Measured by electrocardiogram | Baseline, 3 months, 6 months | 
| Changes in pacing thresholds | Measured during device check | Baseline, 3 months, 6 months | 
| Changes in sensing of R wave | Measured during device check | Baseline, 3 months, 6 months | 
| Changes in lead impedance | Measured during device check | Baseline, 3 months, 6 months | 
| Fluoroscopy time | Time of fluoroscopy use during device implantation | Baseline | 
| Adverse events | Any of the following adverse events: pocket hematoma, pneumothorax, hemothorax, cardiac tamponade, lead dislocation, lead perforation, cardiac implantable device infection | through study completion, an average of one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AV block, His bundle pacing, AV dyssynchrony, AV optimization, AV dromotropathy, First degree AV block, Peak oxygen uptake