Clinical trial NCT06620705: Left Bundle Branch Area Pacing or Biventricular Pacing in AF and Left Ventricular Dysfunction
Official title: Pacing Away from Heart Failure: Left Bundle Branch Area Pacing or Biventricular Pacing in Patients with Atrial Fibrillation and Left Ventricular Dysfunction
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure
Block, Heart
Pacing-Induced Cardiomyopathy
Keywords: pacing
cardiac resynchronization therapy
left bundle branch area pacing
conduction system pacing
heart failure
heart block
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
First posted: 2024-10-01
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized patient and assessor blinded non-inferiority cross-over trial.
Primary purpose: TREATMENT

Brief summary: 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.

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 \&lt; 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).

Eligibility criteria: 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 \&lt; 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 \&gt; 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 \&lt; 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 (\&lt; 6 months)
* NYHA functional class IV heart failure, left ventricular assist device or cardiac transplant

Primary outcomes:
measure: Left ventricular end-systolic volume (LVESV) change
timeFrame: 6 months
Secondary outcomes:
measure: Change in New York Heart Association functional class
timeFrame: 6 months
measure: Change in Minnesota living with heart failure questionnaire
timeFrame: 6 months
measure: Change in 6-minute walking distance
timeFrame: 6 months
measure: Change in QRS duration
timeFrame: 6 months
measure: Change in vectorcardiographic QRS area
timeFrame: 6 months
measure: Change in left ventricular function
timeFrame: 6 months
measure: Change in NT-proBNP
timeFrame: 6 months
measure: Complications
timeFrame: 6 months
measure: Lead pacing thresholds
timeFrame: 6 months
measure: Costs
timeFrame: 6 months
Other outcomes:
Locations:
city: Aarhus N
country: Denmark
facility: Aarhus University Hospital
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
state: Zuid-Holland
Study officials:
affiliation: Leiden University Medical Center, Leiden, the Netherlands
name: Sebastiaan Piers, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: