Synchrony in Cardiac Conduction: Assessing the Effects of Pacing on Cardiac Performance Through Magnetic Resonance Imaging and Advanced ECG-imaging (HARMONY)

Rationale Right ventricular pacing (RVP) is an established and effective therapy for patients with atrioventricular (AV) block. However, frequent RVP has been associated with left ventricular (LV) dyssynchrony and may progess heart failure. Conduction system pacing (CSP), a recently introduced alternative to RVP, aims to preserve physiological ventricular activation by engaging the heart's native conduction system. CSP includes diverse pacing approaches such as selective or non-selective His-bundle pacing, selective left bundle pacing, and LV-septal pacing, each with varying levels of fidelity in reproducing normal conduction. The mechanical impact of these distinct CSP strategies on left and right ventricular (RV) performance remains poorly understood.

Cardiac magnetic resonance imaging (CMR), a non-invasive and highly accurate tool for assessing cardiac structure and function, is uniquely positioned to elucidate the effects of CSP and RVP on cardiac performance. This trial aims to evaluate the comparative mechanical effects of these pacing strategies, potentially identifying the optimal approach for improving outcomes in patients with AV block.

Objective To investigate and compare the effects of CSP and RVP on cardiac performance, as assessed by CMR and electrocardiographic imaging (ECG-imaging).

Main Trial Endpoints The primary endpoints are measures of LV and RV performance assessed via CMR, including: ventricular volumes, ejection fraction (EF), and myocardial strain

Secondary Trial Endpoints

Secondary endpoints include:

Safety and Feasibility:

• Adverse events (e.g., troponin release, lead displacement, arrhythmias, heart failure).
• Technical feasibility (e.g., ease of device implantation, ability to maintain proper pacing).

Electrophysiological Assessment:

• Degree of selectivity in engaging the native conduction system.
• Ventricular activation times as assessed by ECG-imaging.

Trial Design This is a randomized, controlled, single blind, two-center crossover trial. Participants will undergo CSP and RVP in a randomized sequence, each for six months. CMR and ECG-imaging will be performed at 6 months (end of the first pacing phase) and 12 months (end of the second pacing phase).

Trial Population The trial will enroll 88 patients with a normal of at most mildly reduced ejection fraction and an indication for ventricular pacing.

Interventions Participants will undergo CMR and ECG-imaging at 6 months and 12 months.

Ethical Considerations This trial is designed to advance understanding of the mechanical and clinical effects of CSP relative to RVP in patients with AV block. The anticipated benefits include improved cardiac performance and enhanced quality of life. The primary burden to participants is the requirement for an additional CMR scan, which may be perceived as inconvenient or even stressful. The trial minimizes risk by utilizing established clinical procedures and closely monitoring participants for adverse events.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure; AV Block
• Intervention / Treatment: Device: Ventricular pacing

• Study Type: Interventional
• Enrollment (Estimated): 88
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dr. Hopman; Phone Number: +31204444105; Email: l.hopman@amsterdamumc.nl

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:

• Age ≥ 18 years
• Patients with a left ventricular ejection fraction of ≥35%
• Patients with an indication for ventricular pacing and high-degree atrioventricular block where the degree of anticipated RV pacing is >20% including:
• Third degree AV block
• Symptomatic or asymptomatic second-degree AV block
• High degree AV block
• Pace and ablate (AV-node ablation)

Exclusion criteria

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

• CRT indication (patients with heart failure (NYHA >1) in sinus rhythm with left ventricular ejection fraction (LVEF) <35%, QRS duration >150 ms, and left bundle branch block (LBBB) QRS morphology despite optimised medical therapy)
• Inability to undergo CMR (i.e. severe claustrophobia or MRI contraindications)
• Life expectancy <12 months
• Indication for an implantable cardioverter defibrillator
• Presence of severe valve disease or mechanical valves
• Any prior attempt at implantation of an ICD, CRT, CSP
• Permanent AF with rapid ventricular response, unless pace and ablate

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Right ventricular pacing	Device: Ventricular pacing; Participants will undergo conductionsystem pacing and right ventricular pacing in a randomized sequence, each for six months. After each phase, patients will undergo a CMR scan and advanced ECG imaging
Active Comparator: Conduction system pacing	Device: Ventricular pacing; Participants will undergo conductionsystem pacing and right ventricular pacing in a randomized sequence, each for six months. After each phase, patients will undergo a CMR scan and advanced ECG imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary endpoint is LV ejection fraction measured on CMR	At 6 months after crossover

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: February 2, 2025
• First Submitted That Met QC Criteria: February 18, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 18, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Heart Block; Heart Failure; Atrioventricular Block
• Other Study ID Numbers: NL88751.018.25

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: No
• product manufactured in and exported from the U.S.: No