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)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Aortic Valve Stenosis; Complete Heart Block; High Degree Second Degree Atrioventricular Block; Pacemaker-Induced Cardiomyopathy
• Intervention / Treatment: Device: Right ventricular septal pacing followed by left bundle branch area pacing; Device: Left bundle branch area pacing followed by right ventricular septal pacing

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Kansas City Heart Rhythm Institute
  • New Jersey
    • Ridgewood, New Jersey, United States, 07450
      • Valley Health System
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject has at least one of these conduction disturbances:

  1. Symptomatic (or hemodynamically significant) bradycardia or symptomatic persistent atrioventricular block including first-degree and Mobitz I (Wenckebach) or Mobitz type II atrioventricular bock
  2. High-grade atrioventricular block
  3. Third-degree atrioventricular block
• Subject has undergone TAVR (any valve system) in the last four 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% (≥45% if visually estimated at the time of enrollment)
• 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 < 45% if visually estimated at the time of enrollment
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A	Device: Right ventricular septal pacing followed by left bundle branch area pacing; 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.
Experimental: Group B	Device: Left bundle branch area pacing followed by right ventricular septal pacing; 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.

What is the study measuring?

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	Time Frame
Mortality	18 months
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
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

Collaborators and Investigators

• Sponsor: Main Line Health
• Collaborators: Medtronic; Sharpe-Strumia Research Foundation
• Investigators: Principal Investigator: Ali Keramati, MD, Lankenau Heart Institute

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2022
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: September 13, 2022
• First Submitted That Met QC Criteria: September 13, 2022
• First Posted (Actual): September 15, 2022

Study Record Updates

• Last Update Posted (Estimated): December 10, 2024
• Last Update Submitted That Met QC Criteria: December 5, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Atrioventricular Block; Cardiomyopathies; Heart Block
• Other Study ID Numbers: E-22-5212

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No