Conduction System Pacing Versus Biventricular Resynchronization in Patients With Chronic Heart Failure

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of conduction system pacing versus biventricular pacing on death, worsening heart failure, and left ventricular ejection fraction in patients with chronic heart failure with reduced ejection fraction and left bundle branch block.

Official Title
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Conduction System Pacing Versus Biventricular Resynchronization in Patients With Chronic Heart Failure (PhysioSync-HF)

Conditions
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Heart Failure, Left Bundle-Branch Block, Cardiac Resynchronization, Conduction System Pacing

Intervention / Treatment
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* Device: Conduction system pacing
* Device: Biventricular pacing


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or female, age ≥18 years Established diagnosis of symptomatic heart failure (New York Heart Association class II-III) Left ventricular ejection fraction ≤35% in prior 3 months Left bundle branch block (QRS ≥130 ms) Clinical indication for cardiac resynchronization therapy Patients should be clinically stable Patients should receive background standard of care for heart failure with reduced ejection fraction, with the maximum tolerated doses of ACE inhibitor or ARB or ARNI, beta-blocker, and mineralocorticoid receptor antagonist Exclusion criteria: Life expectancy <12 months due to any disease Dementia or advanced cerebrovascular disease NYHA class IV Plan to implant an implantable cardioverter defibrillator (ICD), with or without resynchronization therapy (CRT-D) Enrollment in other clinical trials involving cardiac pacing Pregnancy or pre-menopausal women who do not use regular contraceptive methods Patients unable to understand and sign the consent for participation

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Conduction system pacing<br>Patients will be randomized 1:1 to either conduction system pacing or biventricular pacing. | Device: Conduction system pacing<br>* Pacing from the His-Purkinje system (His-bundle pacing, left bundle branch area pacing, or deep septal pacing).<br>|
| Active Comparator: Biventricular pacing<br>Patients will be randomized 1:1 to either conduction system pacing or biventricular pacing. | Device: Biventricular pacing<br>* Pacing from the coronary sinus and right ventricular leads.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Outcome Measure | Non-inferiority of clinical benefit, a hierarchical composite of all-cause death, any hospitalization for heart failure, any urgent heart failure visit, and left ventricular ejection fraction change at 12 months. The category of clinical benefit of each patient will be determined by assessing the following criteria sequentially, stopping when the event is present: All-cause death: death during follow-up. Hospitalization for heart failure: any hospitalization for heart failure during follow-up. Urgent heart failure visit: any urgent heart failure visit during follow-up. Left ventricular ejection fraction change: the difference between baseline and follow-up, categorized by every 5-point change. The distribution of clinical benefit categories will be compared by ordinal distribution analysis. Non-inferiority margin: odds ratio <1.2. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Key secondary outcome: Cost-effectiveness analysis (dominance) (superiority) | Time-Driven Activity-Based Costing analysis to assess cost-effectiveness of the intervention. | 12 months | 
| Time to composite endpoint of all-cause death, hospitalization for heart failure, or urgent heart failure visit |  | 12 months |