Atrioventricular Node Ablation and Conduction System Pacing in Patients With Well Controlled Permanent Atrial Fibrillation (AF), Heart Failure and Preserved Ejection Fraction: Heart Rate Regularization Versus Medical Rate Control (HF-RELIEF)

Atrioventricular (AV) Node Ablation and Conduction System Pacing in Patients With Well Controlled Permanent Atrial Fibrillation (AF), Heart Failure and Preserved Ejection Fraction: Heart Rate Regularization vs. Medical Rate Control

The goal of this clinical trial is to assess the clinical efficacy of physiological pacing combined with atrioventricular node ablation, in patients with Heart Failure with preserved Ejection Fraction (HFpEF) and well controlled permanent atrial fibrillation.The main question it aims to answer is that heart rate regularization added to physiological pacing - preventing the deleterious effect of right ventricular apical pacing - would reduce mortality and heart failure hospitalizations.

Researchers will compare physiological pacing combined with atrioventricular node ablation (intervention arm) versus optimal pharmacological therapy (control arm) to see if physiological pacing combined with atrioventricular node ablation reduce time to the composite of all-cause mortality or hospitalization due to heart failure or intravenous diuretics (time frame 24 months).

Participants will :

• Be randomized in intervention arm or control arm.
• Visit the clinic 3 months, 12 months and 24 months after the randomization for checkups and tests.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation, Persistent; Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Procedure: pacemaker implantation; Procedure: atrioventricular node ablation; Device: Pacemaker programming

Detailed Description

Heart failure with preserved ejection fraction is a major public health issue affecting 4.9% of general population aged ≥ 60 years. It accounts for more than half of all heart failure hospital admissions. Atrial fibrillation is very common in this diseased population as pathophysiologies are highly interrelated. Atrial fibrillation occurs in two thirds of Heart failure with preserved ejection patients at some point in the natural history and confers a poor prognosis. Therapeutic alternatives are currently limited as patients with permanent Atrial fibrillation and Heart failure with preserved ejection are often treated with drug therapies for lenient rate control.

Recently, the APAF-CRT mortality trial demonstrated a reduction in mortality and hospitalization in Heart Failure and Atrial fibrillation patients treated with Atrioventricular node ablation plus Cardiac Resynchronization Therapy versus pharmacological rate control, irrespective of their baseline Ejection Fraction. The optimal rate regularization achieved with atrioventricular node ablation emerges as the main determinant of reduction in mortality and hospitalization. This conclusion is supported by old robust physiology studies showing that beat-to-beat heart rate irregularity has significant hemodynamic effects and notably decreases cardiac output. However, no specific trials have been conducted in patients with Heart failure with preserved ejection, a population for whom treatment strategies that effectively improve outcomes are sparse. We aim at analyzing the benefit of heart rate regularization and physiological pacing in patients with Heart failure with preserved ejection (Left Ventricular Ejection Fraction ≥ 50%) and permanent Atrial Fibrilation.

We hypothesize that heart rate regularization added to physiological pacing - preventing the deleterious effect of right ventricular apical pacing - would reduce mortality and Heart Failure hospitalizations.

• Study Type: Interventional
• Enrollment (Estimated): 266
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tessa BERGOT, MSc; Phone Number: +33144907033; Email: tessa.bergot@sfcardio.fr

Study Locations

• Belgium
  • Aalst, Belgium, 9300
    • Not yet recruiting
    • OLV Aalst
    • Contact: Ward HEGGERMONT, MD
  • Leuven, Belgium, 3000
    • Not yet recruiting
    • UZ Leuven
    • Contact: Gabor VOROS, MD
  • Ottignies-Louvain-la-Neuve, Belgium, 1340
    • Not yet recruiting
    • Clinique St Pierre Ottignies
    • Contact: Aurélien WAUTERS, MD
• France
  • Brest, France, 29200
    • Not yet recruiting
    • CHRU de Brest - Hopital de la Cavale Blanche
    • Contact: Jacques MANSOURATI, MD
  • Caen, France, 14000
    • Not yet recruiting
    • CHRU de Caen
    • Contact: Pierre OLLITRAULT, MD
  • Chambray-lès-Tours, France, 37170
    • Not yet recruiting
    • CHRU de Tours - Trousseau
    • Contact: Arnaud BISSON, MD
  • Grenoble, France, 38043
    • Not yet recruiting
    • Chu Grenoble Alpes
    • Contact: Pascal DEFAYE, MD
  • La Rochelle, France, 17019
    • Not yet recruiting
    • Groupe Hospitalier La Rochelle-Ré-Aunis
    • Contact: Antoine MILHEM, MD
  • Lille, France, 59000
    • Not yet recruiting
    • CHRU Lille
    • Contact: Christelle MARQUIE, MD
  • Lomme, France, 59462
    • Not yet recruiting
    • GHICL Allome - Hôpital St Philibert
    • Contact: Guillaume VIART, MD
  • Montpellier, France, 34000
    • Not yet recruiting
    • Clinique Millenaire
    • Contact: Nicolas CLEMENTY, MD
  • Nantes, France, 44093
    • Not yet recruiting
    • CHU de Nantes - Hopital Nord Laennec
    • Contact: Jean-Baptiste GOURRAUD, MD
  • Pessac, France, 33604
    • Not yet recruiting
    • CHU de Bordeaux - Hôpital Cardiologique du Haut-Leveque
    • Contact: Pierre BORDACHAR, MD
  • Poitiers, France, 86021
    • Recruiting
    • CHU Poitiers
    • Contact: Rodrigue GARCIA, MD
  • Rouen, France, 76000
    • Not yet recruiting
    • CHU de Rouen
    • Contact: Frédéric ANSELME, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Permanent atrial fibrilation > 6 months
• Preserved Left Ventricular Ejection Fraction ≥ 50%
• ≥ 1 heart failure hospitalization in the previous year
• NYHA (New York Heart Association) score ≥ 2

• Presence of at least one of the following criteria related to diastolic dysfunction:

  • E/e' ratio > 9
  • Left Ventricular mass > 95 g/m2 (female) or > 115 g/m2 (male) with h/R ratio > 0.42
  • NT pro BNP (B-type Natriuretic Peptide) > 365 pg/mL or BNP (B-type Natriuretic Peptide) > 105 pg/mL
• Narrow QRS ≤ 120 ms
• Average heart rate ≤ 110/min on 24 hours Holter monitoring
• Age over 18-year-old
• Capacity to understand the nature of the study, legal ability and willingness to give informed consent
• Patient covered by a social insurance
• Effective contraception and a negative pregnancy test in women of a childbearing age

Exclusion Criteria:

• Patient eligible for atrial fibrilation catheter ablation
• Life expectancy < 12 months
• Severe chronic kidney disease (estimated Glomerular Filtration Rate ≤ 20 ml/1,73 m2)
• Severe respiratory disease (severe chronic obstructive pulmonary disease with Gold ≥ 3 and/or chronic oxygen therapy)
• Class III obesity (Body Mass Index ≥ 40)
• Confirmed or suspected infiltrative cardiomyopathy (amyloidosis, sarcoidosis, Fabry disease, others)
• Obstructive hypertrophic cardiomyopathy
• Previous implanted devices (Pacemaker / Implantable Cardioverter-Defibrillator / Cardiac Resynchronization Therapy)
• Other indication for pacemaker implantation
• Indication for implantable cardioverter-defibrillator
• Ambulatory ≤ 50% of time
• Pregnant women
• Breast-feeding women

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group with pacemaker implantation and atrioventricular node ablation; Pacemaker implantation and atrioventricular node ablation will be performed within a one week period after the randomization.Pharmacological heart failure therapy will be optimized according to current guidelines.	Procedure: pacemaker implantation; The Medtronic 3830 lead should be used as the Conduction System Pacing lead. However, in case of unsuccessful implantation with the 3830 lead, a stylet-driven lead can be used as an alternative.; Procedure: atrioventricular node ablation; Right-sided atrioventricular junction ablation will be attempted first with a radiofrequency catheter. The choice of the catheter will be at the discretion of the physician. The catheter will be advanced to the His Bundle and then slightly withdrawn proximally and caudally in order to target the compact atrioventricular node. Repeated ablation procedures will be recommended during follow-up if regression of atrioventricular block occurs.; Device: Pacemaker programming; The pacemaker device will be programmed in VVIR mode at a lower rate of 75 beats per minute in bipolar mode for sensing and pacing
No Intervention: Control; Conventional care support. The rate control therapy will be optimized to achieve a resting heart rate of <110 beats per minute. Pharmacological heart failure therapy will be optimized according to current guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to the composite of all-cause mortality or hospitalization due to heart failure or intravenous diuretics.	Delay between randomization and death or hospitalization or intravenous diuretics due to heart failure	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to all-cause mortality	Delay between randomization and death (all-cause).	24 months
Time to Cardiovascular mortality	Delay between randomization and death due to cardiovascular disease.	24 months
Time to heart failure hospitalization	Delay between randomization and hospitalization due to heart failure.	24 months
Change in B-type natriuretic peptide level	Evolution of B-type natriuretic peptide (BNP) level between randomization and 24 months follow up visit.	24 months
Major adverse events following pacemaker implantation	Record of safety information about pacemaker implantation procedure	24 months
Major adverse events following atrioventricular node ablation	Record of safety information about atrioventricular node ablation procedure	24 months
Change in New York Heart Association score	Evolution of the functional status measured by New York Heart Association score between randomization and 24 months follow up visit. From II (mild), III (moderate) to IV (severe).	24 months

Collaborators and Investigators

• Sponsor: French Cardiology Society
• Collaborators: ClinSearch; Medtronic France SAS
• Investigators: Principal Investigator: Frédéric ANSELME, MD, CHU de Rouen, France; Study Director: Corentin CHAUMONT, MD, CHU de Rouen, France

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2025
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: February 13, 2025
• First Submitted That Met QC Criteria: February 13, 2025
• First Posted (Actual): February 18, 2025

Study Record Updates

• Last Update Posted (Actual): September 22, 2025
• Last Update Submitted That Met QC Criteria: September 17, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Heart failure; Cardiac Resynchronization Therapy; Conduction System Pacing
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Pathological Conditions, Signs and Symptoms; Heart Failure; Atrial Fibrillation
• Other Study ID Numbers: 2023-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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