Left Bundle Branch Area Pacing for Cardiac Resynchronization Therapy: A Randomized Study

Study Overview
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Brief Summary
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The aim of this study proposal is to compare the effectiveness of two distinct pacing modalities for cardiac resynchronization therapy. Our primary hypothesis is that left bundle branch area pacing (LBBAP) using conventional stylet driven pacemaker leads is an effective resynchronization method that yield to at least similar clinical benefits and outcomes when compare to biventricular pacing.

Detailed Description
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Recently some retrospective or uncontrolled studies were published that compared cardiac resynchronization therapy (CRT) using left bundle branch area pacing (LBBAP) and biventricular pacing (BiV), although with a limited number of patients. Moreover, only one of these studies compared LBBAP + right ventricle stimulation to conventional BiV stimulation prospectively. None of the studies used conventional stylet-driven pacemaker leads for LBBAP. Therefore, the present trial aims to fill-in the gap in the current literature regarding LBBAP for CRT and provide a first randomized head-to-head comparison against CRT. The aim of this study proposal is to compare the effectiveness of two distinct pacing modalities for cardiac resynchronization therapy. Our primary hypothesis is that left bundle branch area pacing (LBBAP) using conventional stylet driven pacemaker leads is an effective resynchronization method that yields to at least similar clinical benefits and outcomes when compared to biventricular pacing. The study is a multicentre, randomized trial comparing LBBAP against biventricular pacing. After characterization of the type device implanted (Pacing or Defibrillator), randomization will occur between both groups in a 1:1 ratio. The trial purpose is to demonstrate the efficacy of LBBAP to treat clinical heart failure in-patient indicated to receive a CRT.

Official Title
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Left Bundle Branch Area Pacing Using Conventional Stylet Driven Pacemaker Leads for Cardiac Resynchronization Therapy: A Randomized Study

Conditions
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Heart Failure With Reduced Ejection Fraction

Intervention / Treatment
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* Procedure: Left Bundle Branch Area Pacing (LBBAP)
* Procedure: Biventricular pacing (BiV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 or above Left Ventricular Ejection Fraction (LVEF) and NYHA meeting one off the previous indications documented with transthoracic echocardiography (TTE) no later than 3 months before randomization. New York Heart Association (NYHA) class II-IV Baseline left bundle branch block and QRS >130ms or QRS >150ms of any morphology or a wide paced QRS duration. Exclusion Criteria: < 18 years age Pregnancy Any unstable medical condition, life expectancy < 12 months Inability to provide consent or to undergo follow-up Narrow QRS duration (≤130ms) or prolonged QRS duration with typical Right Bundle Branch Block (RBBB) morphology on 12 lead ECG and sinus rhythm. Significant hypertrophic cardiomyopathy - any septum abnormality contra-indicating LBBAP implantation (according to physician's evaluation) Patients who are unable to perform a 6 minute walk test (6MWT) Note: patients should be able to perform a 6 minute walk test, but it is not a requirement to have the test performed before the procedure (e.g. due to inability of planning).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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 |
| --- | --- |
| Experimental: LBBAP for CRT-p<br> | Procedure: Left Bundle Branch Area Pacing (LBBAP)<br>* Left bundle branch area pacing using conventional stylet driven pacemaker leads for cardiac resynchronization therapy<br>|
| Experimental: LBBAP for CRT-d<br> | Procedure: Left Bundle Branch Area Pacing (LBBAP)<br>* Left bundle branch area pacing using conventional stylet driven pacemaker leads for cardiac resynchronization therapy<br>|
| Active Comparator: BiV for CRT-p<br> | Procedure: Biventricular pacing (BiV)<br>* Cardiac resynchronization therapy (CRT) using biventricular pacing (BiV)<br>|
| Active Comparator: BiV for CRT-d<br> | Procedure: Biventricular pacing (BiV)<br>* Cardiac resynchronization therapy (CRT) using biventricular pacing (BiV)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of days elapsed from study procedure to first occurrence of one of the following events (combined endpoint) or to study close-out in the total patient population. | First occurrence of one of the following clinical events: death, hospitalization or unscheduled visit for heart failure (HF) or worsening HF symptoms with adaptation of the medical therapy, implant failure for any cause, implantable electronic cardiac device (IECD) re-intervention for any reason during follow-up (Lead Dislocation/phrenic nerve stimulation…) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of procedural characteristics: Operative and fluoroscopic times | Improvement of procedural characteristics: Operative and fluoroscopic times | 1 day | 
| Correction of electrical desynchrony post-implant | Correction of electrical desynchrony post-implant, at 1/6/12 months | 1/6/12 months | 
| Clinical functional response (6MWT) | Clinical functional response as evaluated by the improvement of the 6 Minutes Walk Test (6MWT) at 6 months follow-up | 6 months | 
| Left ventricular reverse remodelling | Left ventricular reverse remodelling at 6 and 12 months follow-up as evaluated by the reduction of the Left Ventricular End-systolic Volume (LVESV) using trans-thoracal echocardiography | 6/12 months | 
| Implantable cardioverter defibrillator (ICD) therapies | ICD therapies at 6 and 12 months | 6/12 months |