Left Bundle Branch Area Pacing or Biventricular Pacing in AF and Left Ventricular Dysfunction

Pacing Away from Heart Failure: Left Bundle Branch Area Pacing or Biventricular Pacing in Patients with Atrial Fibrillation and Left Ventricular Dysfunction

It is unknown whether left bundle branch area pacing (LBBAP) or biventricular pacing best prevents or reverses left ventricular (LV) adverse remodelling in patients with atrial fibrillation (AF) who require ventricular pacing or CRT. This randomized non-inferiority cross-over trial will compare left ventricular end-systolic volume change and secondary endpoints between LBBAP and biventricular pacing in patients with AF and LV dysfunction.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Pacing-Induced Cardiomyopathy; Block, Heart
• Intervention / Treatment: Device: Left bundle branch area pacing; Device: Biventricular pacing

Detailed Description

Rationale: Patients with atrial fibrillation (AF) and left ventricular (LV) dysfunction may require ventricular pacing because of bradycardia, AV junction ablation, or for cardiac resynchronization therapy. Right ventricular (RV) pacing is associated with the risk of adverse LV remodelling and heart failure, in particular in those with pre-existing LV dysfunction. Both LBBAP and biventricular pacing can prevent LV dyssynchrony. It is unknown which pacing mode best prevents or reverses LV adverse remodelling in patients with AF who require ventricular pacing or CRT.

Primary objectives:

1. To compare LVESV change between LBBAP and biventricular pacing in patients with AF and LV dysfunction.

   Secondary objectives:

2. To compare change in quality of life, New York Heart Association functional class, 6-minute walking distance, QRS duration, vectorcardiographic QRS area, left ventricular ejection fraction (LVEF), global longitudinal strain and NT-proBNP between LBBAP and biventricular pacing in patients with AF and LV dysfunction.

Study design: Randomized patient and assessor blinded non-inferiority cross-over trial.

Study population: Patients with permanent AF and LVEF < 50% who require ventricular pacing because of bradycardia, AV junction ablation, or CRT.

Intervention: Patients will be randomized according to a crossover design to first 6 months of LBBAP and then 6 months of biventricular pacing, or vice versa.

After finishing the randomization phase of the study at 12 months, patients will be followed according to routine clinical practice. Clinical follow-up, an ECG, device interrogation and echocardiography will be performed at 36 months (2 years after finishing the randomization phase) in all patients.

Main study parameters/endpoints: New York Heart Association (NYHA) functional class, Minnesota Living with Heart Failure Questionnaire (MLHFQ), 6-minute walking distance, ECG (vectorcardiographic QRS area, QRS duration), echocardiography (LVESV, LVEF, global longitudinal strain), NT-proBNP, lead and device performance (sensing, pacing, expected battery life), complications and costs will be evaluated for each pacing mode.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: For the purpose of this randomized controlled trial, patients will also receive a LBBAP lead. The additional risk of serious adverse events is ~1.5% (lead dislodgement 1.1%, 0.4% acute coronary syndrome [all managed conservatively without further sequelae in prior studies]).(1) Patients who participate in the trial will have 3 extra follow-up visits, 4 extra questionnaires, 3 extra ECGs, 3 extra device interrogations, 3 extra echocardiograms and 4 extra blood samples (5 mL each).

• Study Type: Interventional
• Enrollment (Estimated): 34
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sebastiaan RD Piers, MD, PhD; Phone Number: +31715262020; Email: s.r.d.piers@lumc.nl

Study Locations

• Denmark
  • Aarhus N, Denmark, DK-8200
    • Not yet recruiting
    • Aarhus University Hospital
    • Contact: Jens Kristensen, MD, PhD; Phone Number: +45 7845 0000; Email: jens.kristensen@auh.rm.dk
    • Contact: Mads B Kronborg, MD, PhD
    • Contact: Jens C Nielsen, MD, PhD
    • Contact: Jens Kristensen, MD, PhD
• Netherlands
  • Zuid-Holland
    • Leiden, Zuid-Holland, Netherlands, 2300 RC
      • Recruiting
      • Leiden University Medical Center
      • Contact: Sebastiaan RD Piers, MD, PhD; Phone Number: 0031715262020; Email: s.r.d.piers@lumc.nl
      • Contact: Sebastiaan RD Piers, MD, PhD
      • Contact: Katja Zeppenfeld, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

INCLUSION CRITERIA

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

• Adults ≥18 years with permanent AF and LVEF < 50% who either require ventricular pacing because of bradycardia including patients undergoing AV junction ablation, or have an indication for cardiac resynchronization therapy.
• Expected percentage of ventricular pacing > 40%
• ≥ 3 months of heart failure medication optimization

Of note, patients who already have a device, but require an upgrade to a CRT device, can also be included

EXCLUSION CRITERIA

A potential subject who meets any of the following criteria will be excluded from participation in this study:

• Age < 18 years
• Pregnancy or active pregnancy wish
• Not eligible for implantation of an RV lead, LBBAP lead, or LV lead in the coronary sinus
• Recent valve intervention/surgery or acute myocardial infarction (< 6 months)
• NYHA functional class IV heart failure, left ventricular assist device or cardiac transplant

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Left bundle branch area pacing; 6 months of left bundle branch area pacing.	Device: Left bundle branch area pacing; Pacing of the left bundle branch area using a transvenous pacemaker lead; Other Names: Cardiac resynchronization therapy; Conduction system pacing
Active Comparator: Biventricular pacing; 6 months of biventricular pacing using a RV apex lead and LV lead in the coronary sinus.	Device: Biventricular pacing; Pacing of the right and left ventricle using transvenous pacemaker leads; Other Names: Cardiac resynchronization therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular end-systolic volume (LVESV) change	Left ventricular end-systolic volume change measured by echocardiography	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in New York Heart Association functional class	Change in New York Heart Association functional class (NYHA)	6 months
Change in Minnesota living with heart failure questionnaire	The Minnesota living with heart failure questionnaire (MLHFQ) is a self-administered disease-specific questionnaire for patients with heart failure, comprising 21 items rated on six-point Likert scales, representing different degrees of impact of heart failure on quality of life, from 0 (none) to 5 (very much). It provides a total score (range 0-105, from best to worst quality of life).	6 months
Change in 6-minute walking distance	Change in 6-minute walking distance	6 months
Change in QRS duration	Change in QRS duration on the 12-lead ECG	6 months
Change in vectorcardiographic QRS area	Change in vectorcardiographic QRS area on the vectorcardiogram reconstructed from a regular 12-lead ECG	6 months
Change in left ventricular function	Change in left ventricular function ejection fraction and global longitudinal strain on echocardiography	6 months
Change in NT-proBNP	Change in NT-proBNP as a heart failure biomarker	6 months
Complications	Complications related to device and leads	6 months
Lead pacing thresholds	Lead pacing thresholds, expressed as volts at pulse width (e.g. 0.4 V @ 0.4 ms). A lower pacing threshold is better.	6 months
Costs	Costs related to the device and leads	6 months

Collaborators and Investigators

• Sponsor: srdpiers
• Collaborators: Aarhus University Hospital
• Investigators: Principal Investigator: Sebastiaan Piers, MD, PhD, Leiden University Medical Center, Leiden, The Netherlands

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: September 10, 2024
• First Submitted That Met QC Criteria: September 26, 2024
• First Posted (Actual): October 1, 2024

Study Record Updates

• Last Update Posted (Actual): October 1, 2024
• Last Update Submitted That Met QC Criteria: September 26, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: cardiac resynchronization therapy; heart failure; left bundle branch area pacing; pacing; conduction system pacing; heart block
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Heart Failure; Heart Block; Cardiomyopathies; Ventricular Dysfunction; Ventricular Dysfunction, Left
• Other Study ID Numbers: NL84372.058.23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data will be shared with other researchers whenever reasonable and of potential benefit for patients.
• IPD Sharing Time Frame: After completion of the study and publication, the data will be shared with other researchers whenever reasonable and of potential benefit for patients.
• IPD Sharing Access Criteria: Whenever reasonable and of potential benefit for patients.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

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.: Yes