Impact of Left Bundle Branch Area Pacing vs. Right Ventricular Pacing in Atrioventricular Block (LEAP-Block)

Overview

This is a multicenter, randomized controlled study. The aim of this study is to compare the impact of LBBAP on left ventricular function as compared with traditional right ventricular pacing in patients with atrioventricular block.

Full Title of Study: “Impact of Left Bundle Branch Area Pacing vs. Right Ventricular Pacing in Atrioventricular Block (LEAP-Block): A Randomized Controlled Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Outcomes Assessor)
  • Study Primary Completion Date: June 30, 2024

Detailed Description

LEAP-BLOCK is a prospective, multi-center, randomized controlled trial that is designed to determine whether left bundle branch area pacing (LBBAP) may reduce the risk of RV ventricular pacing induced cardiac dysfunction as compared with traditional RV pacing (RVP) in patients with atrioventricular (AV) block and normal LV function (LVEF≥50%) who require high percent of ventricular pacing. The primary aim of this trial is to compare the time to first event (composite of all-cause mortality and newly heart failure hospitalization and device upgrade due to heart failure) between LBBAP and RVP group in patients with AV block. Patients with AV block and normal LV function who require high burden of ventricular pacing (expected >40%) will be randomized to LBBAP or RVP group for therapy. Patients will be followed at least every 3 months for clinical status and every 6 months for echocardiographic evaluation until the study closure.

Interventions

  • Device: Left bundle branch area pacing
    • Left bundle branch area pacing(LBBAP) is a novel physiological pacing form for ventricular pacing. In patients received LBBAP, the pacing lead will be placed at left bundle branch area to achieve narrow paced QRS duration.
  • Device: Right ventricular pacing
    • Right ventricular pacing is the traditional pacing modality for ventricular pacing. The pacing lead was placed in the apex or septum of right ventricle.

Arms, Groups and Cohorts

  • Experimental: LBBAP group
    • AV block patients randomized to left bundle branch area pacing
  • Active Comparator: RVP group
    • AV block patients randomized to right ventricular pacing group

Clinical Trial Outcome Measures

Primary Measures

  • The primary endpoint is the time to a first event of composite outcomes, including all-cause death, hospitalization for heart failure, and an upgrade to cardiac resynchronization therapy due to pacing induced heart failure.
    • Time Frame: Within two years after device implantation
    • All-cause death: including cardiovascular and non-cardiovascular deaths. Hospitalization for heart failure: an unplanned outpatient or emergency department visit or inpatient hospitalization in which the patient presented with signs and symptoms consistent with heart failure and required medication therapy. Upgrade to cardiac resynchronization therapy (CRT): Upgrade from dual-chamber pacemaker to CRT-Pacemaker/CRT-Defibrillator due to impaired LV function (LVEF decrease to 40% or less).

Secondary Measures

  • Rate of the composite outcomes of all-cause death and/or hospitalization for heart failure
    • Time Frame: Within 2 years after device implantation
    • All-cause death: including cardiovascular and non-cardiovascular deaths. Hospitalization for heart failure: an unplanned outpatient or emergency department visit or inpatient hospitalization in which the patient presented with signs and symptoms consistent with heart failure and required medication therapy.
  • Rate of the composite outcomes of hospitalization for heart failure and/or an upgrade to cardiac resynchronization therapy due to pacing induced heart failure.
    • Time Frame: Within 2 years after device implantation
    • Hospitalization for heart failure: an unplanned outpatient or emergency department visit or inpatient hospitalization in which the patient presented with signs and symptoms consistent with heart failure and required medication therapy. Upgrade to cardiac resynchronization therapy: Upgrade from dual chamber pacemaker to CRT-P/CRT-D due to impaired LV function (LVEF decrease to 40% or less).
  • Rate of the composite outcomes of LVEF <50%, and/or an increase in LVESV ≥15% during follow-up as compared with the value at randomization
    • Time Frame: Within 2 years after device implantation
    • Echocardiography will be assessed every 6 month during follow-up to determine whether the LVEF is less than 50% and/or the LVESV is increased by 15% or more.
  • The value of LVEF and LVESV assessed by echocardiography at 1-year and 2-year follow-up
    • Time Frame: 24 months
    • Echocardiography will be assessed at 1-year, and 2-year follow-up and the absolute value of LVEF and LVESV will be compared between two groups.
  • The time to a first event of LVEF <50% and decrease in LVEF by ≥ 10% during 2 years follow-up as compared with the value at randomization.
    • Time Frame: 24 months
    • Echocardiography will be assessed every 6 month during follow-up to determine whether the LVEF is less than 50% and decreased by 15% or more as compared with the value at randomization.
  • The immediate success rate of the LBBAP procedure
    • Time Frame: 1 weeks
    • Successful LBBAP procedure is identified according to ECG and intracardiac electrogram (IEGM) during the procedure. All LBBAP procedures will be categorized as selective left bundle branch pacing (S-LBBP), non-selective left bundle branch pacing(NS-LBBP), or left ventricular septal pacing (LVSP).
  • The rate of procedure and Device related complications
    • Time Frame: 24 months
    • Procedure complications include pneumothorax, hemothorax, and air embolism. Device related complications include lead and pocket complications.
  • Changes in Pacing parameters and ECG characteristics.
    • Time Frame: 24 months
    • Pacing parameters include pacing thresholds (ventricle), Sense ampitude (ventricle), Impedance (ventricle). ECG characteristics include paced QRS duration and QRS morphology, etc.
  • The occurrence of LV dyssynchrony
    • Time Frame: 24 months
    • The occurrence of LV dyssynchrony will be evaluated by echocardiography during 2-year follow-up.
  • Atrial high-rate episodes recorded by the pacemaker
    • Time Frame: 24 months
    • Atrial high-rate episodes recorded in the pacemaker will be followed during two years of follow-up
  • The long-term success rate of LBBAP
    • Time Frame: 24 months
    • In LBBAP group, the successful LBBAP will be identified according ECG features at 2-years follow-up

Participating in This Clinical Trial

Inclusion Criteria

  • a. Adult patients aged 18-90; – b. AV block patients with ventricular pacing indications and the expected rate of ventricular pacing(VP)> 40%, including (a)Third-degree AV block; (b) Second degree AV block (type II); (c) intermittent advanced AV block with expected VP>40%; (d)Symptomatic first degree AV block and PR interval on ECG ≥ 250ms; – c. The subject is able to receive a pectoral implant; – d. The subject is willing and able to comply with the protocol; – e. The subject is expected to remain available for follow-up visits at the study centers. – f. Subject or authorized legal guardian or representative has signed and dated the study Subject Informed Consent Exclusion Criteria:

  • a. Baseline echocardiographic assessment of patients with impaired LV function (LVEF<50%); – b. Having difficulties in follow-up: Those who cannot accept 2-year follow-up on time due to physical condition or other reasons; – c. Patients with persistent atrial fibrillation; – d. Pacemaker replacement without new implanted ventricular electrodes; – e. Patients with implantable cardioverter-defibrillator (ICD) indications; – f. Surgery is required within 1 year due to severe structural heart disease; – g. Patients with tricuspid mechanical valve replacement, or congenital heart disease (including transposition of the great arteries, or permanent left superior vena cava, etc), or AV block resulting from: (a) Hypertrophic cardiomyopathy(HCM)vpost (modified) Morrow surgery, (b) ventricular septal defect repair; and those who are unlikely to achieve successful LBBAP procedure.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 90 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Fu Wai Hospital, Beijing, China
  • Collaborator
    • Beijing Anzhen Hospital
  • Provider of Information About this Clinical Study
    • Principal Investigator: Fan Xiaohan, Professor, MD, PhD – Chinese Academy of Medical Sciences, Fuwai Hospital
  • Overall Official(s)
    • Xiaohan Fan, PhD., Study Chair, Fuwai Hospital
  • Overall Contact(s)
    • Xiaofei Li, M.D., +8617801013995, lixiaofei0103@163.com

References

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Vijayaraman P, Naperkowski A, Subzposh FA, Abdelrahman M, Sharma PS, Oren JW, Dandamudi G, Ellenbogen KA. Permanent His-bundle pacing: Long-term lead performance and clinical outcomes. Heart Rhythm. 2018 May;15(5):696-702. doi: 10.1016/j.hrthm.2017.12.022. Epub 2017 Dec 20.

Cho SW, Gwag HB, Hwang JK, Chun KJ, Park KM, On YK, Kim JS, Park SJ. Clinical features, predictors, and long-term prognosis of pacing-induced cardiomyopathy. Eur J Heart Fail. 2019 May;21(5):643-651. doi: 10.1002/ejhf.1427. Epub 2019 Feb 8.

Tayal B, Fruelund P, Sogaard P, Riahi S, Polcwiartek C, Atwater BD, Gislason G, Risum N, Torp-Pedersen C, Kober L, Kragholm KH. Incidence of heart failure after pacemaker implantation: a nationwide Danish Registry-based follow-up study. Eur Heart J. 2019 Nov 21;40(44):3641-3648. doi: 10.1093/eurheartj/ehz584.

Huang W, Su L, Wu S, Xu L, Xiao F, Zhou X, Mao G, Vijayaraman P, Ellenbogen KA. Long-term outcomes of His bundle pacing in patients with heart failure with left bundle branch block. Heart. 2019 Jan;105(2):137-143. doi: 10.1136/heartjnl-2018-313415. Epub 2018 Aug 9.

Abdelrahman M, Subzposh FA, Beer D, Durr B, Naperkowski A, Sun H, Oren JW, Dandamudi G, Vijayaraman P. Clinical Outcomes of His Bundle Pacing Compared to Right Ventricular Pacing. J Am Coll Cardiol. 2018 May 22;71(20):2319-2330. doi: 10.1016/j.jacc.2018.02.048. Epub 2018 Mar 10.

Vijayaraman P, Dandamudi G. Anatomical approach to permanent His bundle pacing: Optimizing His bundle capture. J Electrocardiol. 2016 Sep-Oct;49(5):649-57. doi: 10.1016/j.jelectrocard.2016.07.003. Epub 2016 Jul 11. Review.

Li X, Li H, Ma W, Ning X, Liang E, Pang K, Yao Y, Hua W, Zhang S, Fan X. Permanent left bundle branch area pacing for atrioventricular block: Feasibility, safety, and acute effect. Heart Rhythm. 2019 Dec;16(12):1766-1773. doi: 10.1016/j.hrthm.2019.04.043. Epub 2019 Apr 29.

Li X, Qiu C, Xie R, Ma W, Wang Z, Li H, Wang H, Hua W, Zhang S, Yao Y, Fan X. Left bundle branch area pacing delivery of cardiac resynchronization therapy and comparison with biventricular pacing. ESC Heart Fail. 2020 Aug;7(4):1711-1722. doi: 10.1002/ehf2.12731. Epub 2020 May 13.

Sharma PS, Dandamudi G, Naperkowski A, Oren JW, Storm RH, Ellenbogen KA, Vijayaraman P. Permanent His-bundle pacing is feasible, safe, and superior to right ventricular pacing in routine clinical practice. Heart Rhythm. 2015 Feb;12(2):305-12. doi: 10.1016/j.hrthm.2014.10.021. Epub 2014 Oct 22.

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