Impact of Left Bundle Branch Area Pacing vs. Right Ventricular Pacing in Atrioventricular Block (LEAP-Block)

Study Overview
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Brief Summary
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This is a multicenter, randomized controlled study. The aim of this study is to compare the impact of LBBAP on left ventricular function as compared with traditional right ventricular pacing in patients with atrioventricular block.

Detailed Description
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LEAP-BLOCK is a prospective, multi-center, randomized controlled trial that is designed to determine whether left bundle branch area pacing (LBBAP) may reduce the risk of RV ventricular pacing induced cardiac dysfunction as compared with traditional RV pacing (RVP) in patients with atrioventricular (AV) block and normal LV function (LVEF≥50%) who require high percent of ventricular pacing. The primary aim of this trial is to compare the time to first event (composite of all-cause mortality and newly heart failure hospitalization and device upgrade due to heart failure) between LBBAP and RVP group in patients with AV block. Patients with AV block and normal LV function who require high burden of ventricular pacing (expected >40%) will be randomized to LBBAP or RVP group for therapy. Patients will be followed at least every 3 months for clinical status and every 6 months for echocardiographic evaluation until the study closure.

Official Title
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Impact of Left Bundle Branch Area Pacing vs. Right Ventricular Pacing in Atrioventricular Block (LEAP-Block): A Randomized Controlled Trial

Conditions
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Atrioventricular Block, Left Bundle Branch Area Pacing, Right Ventricular Pacing, Heart Failure

Intervention / Treatment
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* Device: Left bundle branch area pacing
* Device: Right ventricular pacing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: a. Adult patients aged 18-90; b. AV block patients with ventricular pacing indications and the expected rate of ventricular pacing(VP)> 40%, including (a)Third-degree AV block; (b) Second degree AV block (type II); (c) intermittent advanced AV block with expected VP>40%; (d)Symptomatic first degree AV block and PR interval on ECG ≥ 250ms; c. The subject is able to receive a pectoral implant; d. The subject is willing and able to comply with the protocol; e. The subject is expected to remain available for follow-up visits at the study centers. f. Subject or authorized legal guardian or representative has signed and dated the study Subject Informed Consent Exclusion Criteria: a. Baseline echocardiographic assessment of patients with impaired LV function (LVEF<50%); b. Having difficulties in follow-up: Those who cannot accept 2-year follow-up on time due to physical condition or other reasons; c. Patients with persistent atrial fibrillation; d. Pacemaker replacement without new implanted ventricular electrodes; e. Patients with implantable cardioverter-defibrillator (ICD) indications; f. Surgery is required within 1 year due to severe structural heart disease; g. Patients with tricuspid mechanical valve replacement, or congenital heart disease (including transposition of the great arteries, or permanent left superior vena cava, etc), or AV block resulting from: (a) Hypertrophic cardiomyopathy(HCM)vpost (modified) Morrow surgery, (b) ventricular septal defect repair; and those who are unlikely to achieve successful LBBAP procedure.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LBBAP group<br>AV block patients randomized to left bundle branch area pacing | Device: Left bundle branch area pacing<br>* Left bundle branch area pacing(LBBAP) is a novel physiological pacing form for ventricular pacing. In patients received LBBAP, the pacing lead will be placed at left bundle branch area to achieve narrow paced QRS duration.<br>|
| Active Comparator: RVP group<br>AV block patients randomized to right ventricular pacing group | Device: Right ventricular pacing<br>* Right ventricular pacing is the traditional pacing modality for ventricular pacing. The pacing lead was placed in the apex or septum of right ventricle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint is the time to a first event of composite outcomes, including all-cause death, hospitalization for heart failure, and an upgrade to cardiac resynchronization therapy due to pacing induced heart failure. | All-cause death: including cardiovascular and non-cardiovascular deaths. Hospitalization for heart failure: an unplanned outpatient or emergency department visit or inpatient hospitalization in which the patient presented with signs and symptoms consistent with heart failure and required medication therapy. Upgrade to cardiac resynchronization therapy (CRT): Upgrade from dual-chamber pacemaker to CRT-Pacemaker/CRT-Defibrillator due to impaired LV function (LVEF decrease to 40% or less). | Within two years after device implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of the composite outcomes of all-cause death and/or hospitalization for heart failure | All-cause death: including cardiovascular and non-cardiovascular deaths. Hospitalization for heart failure: an unplanned outpatient or emergency department visit or inpatient hospitalization in which the patient presented with signs and symptoms consistent with heart failure and required medication therapy. | Within 2 years after device implantation | 
| Rate of the composite outcomes of hospitalization for heart failure and/or an upgrade to cardiac resynchronization therapy due to pacing induced heart failure. | Hospitalization for heart failure: an unplanned outpatient or emergency department visit or inpatient hospitalization in which the patient presented with signs and symptoms consistent with heart failure and required medication therapy. Upgrade to cardiac resynchronization therapy: Upgrade from dual chamber pacemaker to CRT-P/CRT-D due to impaired LV function (LVEF decrease to 40% or less). | Within 2 years after device implantation | 
| Rate of the composite outcomes of LVEF <50%, and/or an increase in LVESV ≥15% during follow-up as compared with the value at randomization | Echocardiography will be assessed every 6 month during follow-up to determine whether the LVEF is less than 50% and/or the LVESV is increased by 15% or more. | Within 2 years after device implantation | 
| The value of LVEF and LVESV assessed by echocardiography at 1-year and 2-year follow-up | Echocardiography will be assessed at 1-year, and 2-year follow-up and the absolute value of LVEF and LVESV will be compared between two groups. | 24 months | 
| The time to a first event of LVEF <50% and decrease in LVEF by ≥ 10% during 2 years follow-up as compared with the value at randomization. | Echocardiography will be assessed every 6 month during follow-up to determine whether the LVEF is less than 50% and decreased by 15% or more as compared with the value at randomization. | 24 months | 
| The immediate success rate of the LBBAP procedure | Successful LBBAP procedure is identified according to ECG and intracardiac electrogram (IEGM) during the procedure. All LBBAP procedures will be categorized as selective left bundle branch pacing (S-LBBP), non-selective left bundle branch pacing(NS-LBBP), or left ventricular septal pacing (LVSP). | 1 weeks | 
| The rate of procedure and Device related complications | Procedure complications include pneumothorax, hemothorax, and air embolism. Device related complications include lead and pocket complications. | 24 months | 
| Changes in Pacing parameters and ECG characteristics. | Pacing parameters include pacing thresholds (ventricle), Sense ampitude (ventricle), Impedance (ventricle). ECG characteristics include paced QRS duration and QRS morphology, etc. | 24 months | 
| The occurrence of LV dyssynchrony | The occurrence of LV dyssynchrony will be evaluated by echocardiography during 2-year follow-up. | 24 months | 
| Atrial high-rate episodes recorded by the pacemaker | Atrial high-rate episodes recorded in the pacemaker will be followed during two years of follow-up | 24 months | 
| The long-term success rate of LBBAP | In LBBAP group, the successful LBBAP will be identified according ECG features at 2-years follow-up | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrioventricular Block, Left bundle branch area pacing, Right ventricular pacing