LVSP vs RVP in Patients With AV Conduction Disorders

Summary

Rationale:

Permanent cardiac pacing is the only available therapy in patients with atrioventricular (AV) conduction disorders and can be life-saving. Right ventricular pacing (RVP), the routine clinical practice for decades in these patients, is non-physiologic, leads to dyssynchronous electrical and mechanical activation of the ventricles, and may cause pacing-induced cardiomyopathy and heart failure.

Left ventricular septal pacing (LVSP) is an emerging form of physiologic pacing that can possibly overcome the adverse effects of RVP.

Study design and hypotheses:

The LEAP trial is a multi-center investigator-initiated, prospective, randomized controlled, open label, blinded endpoint evaluation (PROBE) study that compares LVSP with conventional RVP. A total of four hundred seventy patients with a class I or IIa indication for pacemaker implantation due to AV conduction disorders and an expected ventricular pacing percentage \>20% will be randomized 1:1 to LVSP or RVP. The primary endpoint is a composite endpoint of all-cause mortality, hospitalization for heart failure and a more than 10% decrease in left ventricular ejection fraction (LVEF) in absolute terms leading to a LVEF below 50% at one year follow-up. LVSP is anticipated to result in improved outcomes.

Secondary objectives are to evaluate whether LVSP is cost-effective and associated with an improved quality of life (QOL) as compared to RVP. Quality of life is expected to improve with LVSP and reduced healthcare resource utilizations are expected to ensure lower costs in the LVSP group during follow-up, despite initial higher costs of the implantation.

Study design: Multi-center investigator-initiated, prospective, randomized controlled, open label, blinded endpoint evaluation (PROBE) study.

Study population: Adult patients with a bradycardia-pacing indication because of AV conduction disorders with an expected ventricular pacing percentage of ≥ 20% and a left ventricular ejection fraction (LVEF) \>/= 40%. Four hundred seventy patients will be randomized 1:1 to LVSP or RVP.

Intervention: LVSP vs RVP.

Main study parameters/endpoints:

The primary endpoint is a composite of all-cause mortality, hospitalization for heart failure, and a more than 10% point decrease in left ventricular ejection fraction (LVEF) leading to an LVEF below 50%, which as a binary combined endpoint will be determined at one year follow-up.

Secondary endpoints are:

* Time to first occurrence of all cause mortality or hospitalization for heart failure.
* Time to first occurrence of all cause mortality.
* Time to first occurrence of hospitalization for heart failure.
* Time to first occurrence of atrial fibrillation (AF) de novo.
* The echocardiographic changes in LVEF at one year.
* The echocardiographic changes in diastolic (dys-)function at one year.
* The occurrence of pacemaker related complications.
* Quality of life (QOL), cost-effectiveness analyses (CEA) and budget impact analysis (BIA).

The secondary endpoints (other than echocardiographic LVEF change) will be determined at the end of the follow-up period, when the last included patient has reached one year follow-up. The individual follow-up time for patients at this time point will vary with a minimum of one year.

Conditions

• Cardiac Pacing
• Pacing-Induced Cardiomyopathy
• Conduction System Pacing
• Left Ventricular Septal Pacing
• Atrioventricular Block

Interventions

PROCEDURE

Left ventricular septal pacing

In the LVSP group, instead of placing the standard RV lead, the commercially available 3830 Select Secure (Medtronic, Minneapolis, USA) lead is introduced via standard transvenous approach and positioned against the right ventricular side of the IVS by using the commercially available non-deflectable septal delivery sheath (C315, Medtronic, Minneapolis, USA) under fluoroscopic guidance. Subsequently this pacing lead is advanced/screwed through the interventricular septum until the left ventricular septum is reached. Accurate lead position at the left ventricular septum will be determined anatomically using fluoroscopy, and electrically by evaluating local electrograms and changes in paced electrocardiogram morphology. In case of unsuccessful lead positioning in the left ventricular septum, the Select Secure lead may be placed at the His bundle region (natural conduction system of the heart) or in the right ventricle according to the physician's discretion.

PROCEDURE

Right ventricular pacing

In the RVP group, the ventricular pacing lead is positioned in the right ventricle.

Sponsors & Collaborators

• ZonMw: The Netherlands Organisation for Health Research and Development

  collaborator OTHER

• Medtronic

  collaborator INDUSTRY

• Maastricht University

  lead OTHER

Principal Investigators

• Justin Luermans, MD PhD · Department of Cardiology

• Kevin Vernooy, MD PhD · Department of Cardiology

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-05-01

Primary Completion

2025-05-01

Completion

2025-05-01

Countries

• Belgium
• Czechia
• Italy
• Netherlands
• Poland
• Spain
• Switzerland

Study Locations