Comparison of Left Bundle Branch Area Versus Right Ventricular Septal Pacing in Patients With High-degree Conduction Disease After Transcatheter Aortic Valve Replacement (Left Bundle BRAVE)

Study Overview
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Brief Summary
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The purpose of the study is to investigate the superiority of chronic left bundle branch area pacing compared to traditional right ventricular (RV) septal pacing in patients with high-grade conduction disease after transcatheter aortic valve replacement (TAVR). In this investigator initiated, multicenter, prospective, double-blinded, crossover study, chronic left bundle branch area pacing will be compared to chronic right ventricular septal pacing using echocardiographic measures of left ventricular systolic function in patients with a high cumulative ventricular pacing burden after TAVR.

Official Title
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Comparison of Left Bundle Branch Area Versus Right Ventricular Septal Pacing in Patients With High-degree Conduction Disease After Transcatheter Aortic Valve Replacement

Conditions
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Complete Heart Block, High Degree Second Degree Atrioventricular Block, Pacemaker-Induced Cardiomyopathy, Aortic Valve Stenosis

Intervention / Treatment
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* Device: Right ventricular septal pacing followed by left bundle branch area pacing
* Device: Left bundle branch area pacing followed by right ventricular septal pacing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has at least one of these conduction disturbances: Symptomatic (or hemodynamically significant) bradycardia or symptomatic persistent atrioventricular block including first-degree and Mobitz I (Wenckebach) or Mobitz type II atrioventricular bock High-grade atrioventricular block Third-degree atrioventricular block Subject has undergone TAVR (any valve system) in the last two weeks Subject is receiving a first-time pacemaker implant Subject's most recent documented ejection fraction (by any method) within the past 90 days prior to study enrollment is > 50% Subject is a male or female at least 18 years old at the time of consent Subject is able to receive a left sided pectoral implant Exclusion Criteria: Subject has ever had a previous or has an existing implantable pulse generator (IPG), implantable cardiac defibrillator (ICD) or biventricular (BiV) implant Subject has more than mild para-valvular regurgitation following TAVR implantation. Subject has LVEF ≤ 50 Subject is indicated for a biventricular pacing device (CRT-P or CRT-D). Subject is enrolled in a concurrent study that may confound the results of this study Subject has a mechanical heart valve Subject is pregnant, or of childbearing potential and not on a reliable form of birth control Subject status post heart transplant Subject life expectancy less than 2 years

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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br> | Device: Right ventricular septal pacing followed by left bundle branch area pacing<br>* All patients will undergo implantation of right ventricular septal lead, left bundle branch area lead, and atrial lead in the absence of permanent atrial fibrillation with a CRT-pacing generator. Patients will be randomized to pacing protocols based on group assignment and crossover during the study.<br>|
| Experimental: Group B<br> | Device: Left bundle branch area pacing followed by right ventricular septal pacing<br>* All patients will undergo implantation of right ventricular septal lead, left bundle branch area lead, and atrial lead in the absence of permanent atrial fibrillation with a CRT-pacing generator. Patients will be randomized to pacing protocols based on group assignment and crossover during the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in global longitudinal strain (GLS%) | Primary efficacy outcome | 9 months | 
| Change in left ventricular ejection fraction (LVEF%) | Primary efficacy outcome | 9 months | 
| Composite of left bundle branch area pacing lead septal myocardial or coronary artery perforation, lead dislodgment, and repeat procedures related to left bundle branch area lead implantation | Primary safety endpoint | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events related to device function |  | 18 months | 
| Quality of life measured using the Minnesota Living with Heart Failure questionnaire (MLHQ) |  | 9 months | 
| Functional capacity measured using the New York Heart Association functional classification (NYHA) |  | 9 months | 
| Six minute walk test score |  | 9 months | 
| Hospitalizations for heart failure |  | 18 months | 
| Mortality |  | 18 months | 
| Right ventricular global longitudinal strain (RVGLS%) |  | 9 months | 
| Left ventricular mechanical systolic dyssynchrony indexed to heart rate (SDI) |  | 9 months | 
| Interventricular mechanical delay (IVMD) |  | 9 months | 
| Left ventricular end-systolic volume |  | 9 months | 
| Left ventricular stroke volume |  | 9 months | 
| Severity of tricuspid regurgitation |  | 18 months | 
| Severity of mitral regurgitation |  | 18 months | 
| Left bundle branch area pacing lead pacing threshold |  | 18 months | 
| Left bundle branch area pacing lead sensed R wave amplitude |  | 18 months | 
| Left bundle branch area pacing lead impedence |  | 18 months | 
| Brain natriuretic peptide or N-terminal pro-brain natriuretic peptide concentration |  | 9 months |