His-Bundle Corrective Pacing in Heart Failure

Study Overview
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Brief Summary
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The investigators aim to prospectively evaluate the efficacy and mechanism of benefit of His-bundle pacing enhanced cardiac resynchronization therapy (His-CRT) vs. cardiac resynchronization therapy (BIV-CRT) in patients with heart failure and right bundle branch block (RBBB).

Detailed Description
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In this prospective, randomized, multi-center clinical trial, the investigators aim to prospectively evaluate the efficacy and mechanism of benefit of His-bundle pacing enhanced cardiac resynchronization therapy (His-CRT) vs. cardiac resynchronization therapy (BIV-CRT) in patients with Right Bundle Branch Block (RBBB) Electrocardiogram (ECG) Pattern by assessing the improvement in left ventricular ejection fraction (LVEF) in the His-CRT vs. BIV-CRT arm at 6 months, and by evaluating changes in ECG biomarkers, NT-pro-brain natriuretic peptide (NT-proBNP) levels, and echocardiography biomarkers (left ventricular volumes, strain contractility, and dyssynchrony), as well as temporal changes in functional status and quality of life in the His-CRT vs. BIV-CRT arm at 6, 12, and 24 months.

Official Title
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His-Bundle Corrective Pacing in Heart Failure

Conditions
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Right Bundle-Branch Block, Heart Failure, His-bundle Pacing, Cardiac Resynchronization Therapy

Intervention / Treatment
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* Procedure: His-CRT implantation
* Procedure: BIV-CRT implantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older (no upper age limit) Optimal medical therapy for heart failure by current guidelines Class IIa or IIb guideline-based indication for CRT-D implant in RBBB patients, including one of the following: New York Heart Association (NYHA) class II HF symptoms, LVEF ≤ 30% and QRS≥ 150 ms (IIb); OR NYHA class III-IV a HF, LVEF ≤ 35%, and QRS duration ≥ 150 ms (IIa); OR NYHA class III-IV a HF, LVEF ≤ 35%, and QRS duration 120-149 ms (IIb) Exclusion Criteria: Unable to obtain most recent imaging data from echocardiogram within 1 year prior to date of randomization Left bundle branch block (LBBB) or intraventricular conduction delay (IVCD) ECG morphology Unable or unwilling to follow study protocol Less than 12 months life expectancy at consent Pregnancy or planned pregnancy during duration of the study On heart transplant list or likely to undergo heart transplant

Ages Eligible for Study
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Minimum Age: 18 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: His-CRT implantation<br>His-CRT implantation includes implantation of three leads, an endocardial right atrial lead, an endocardial right ventricular lead, and an endocardial His-bundle pacing leads directly pacing the intrinsic conduction system. | Procedure: His-CRT implantation<br>* The pathophysiological process is utilized in His-Bundle corrective pacing, resulting in a faster and more homogeneous activation of the heart pacing directly via the intrinsic conduction system of the heart accompanied by a right atrial endocardial lead and a right ventricular endocardial lead.<br>|
| Active Comparator: BIV-CRT implantation<br>BIV-CRT implantation includes implantation of three leads, an endocardial right atrial lead, an endocardial right ventricular lead, and an epicardial left ventricular lead implanted in a branch of the coronary sinus. | Procedure: BIV-CRT implantation<br>* Biventricular cardiac resynchronization therapy has been shown to improve outcomes by delivering synchronized electrical stimuli to the right and left ventricles utilizing an an endocardial right atrial lead, an endocardial right ventricular lead, and an epicardial left ventricular lead implanted in a branch of the coronary sinus.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Left Ventricular Ejection Fraction at 6 months with His-CRT vs. BIV-CRT, in heart failure patients with Right bundle branch block (RBBB) | The effect of His-CRT vs. BIV-CRT on left ventricular ejection fraction (as a percentage) measured during an echocardiography imaging study will be analyzed using an analysis of covariance model for changes in LVEF from pre-implantation (baseline) to post-implantation (6 months follow-up), with randomized treatment group as the factor of interest, and baseline LVEF as a covariate. A t-test will be performed using this model to compare the adjusted group means, and a confidence interval will be constructed for their difference. | 6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the mechanism of benefit with His-CRT vs. BIV-CRT by evaluating changes in ECG biomarkers | Secondary endpoint measured on a continuous scale of paced ventricular depolarization (QRS) duration in the His-CRT vs. BIV-CRT arm | 6 months | 
| Assess the mechanism of benefit with His-CRT vs. BIV-CRT by evaluating changes in echocardiographic left ventricular end-systolic volume (LVESV) | Secondary endpoint measured from echocardiography on left ventricular end-systolic volume (LVESV) in the His-CRT vs. BIV-CRT arm | 6 months | 
| Assess the mechanism of benefit with His-CRT vs. BIV-CRT by evaluating changes in echocardiographic left ventricular end-diastolic volume (LVEDV) | Secondary endpoint measured from echocardiography on left ventricular end-diastolic volume (LVEDV) in the His-CRT vs. BIV-CRT arm | 6 months | 
| Assess the mechanism of benefit with His-CRT vs. BIV-CRT by evaluating changes in NT-proBNP | Secondary endpoint of NT-proBNP in the His-CRT vs. BIV-CRT arm | 6 months |