Optimising Pacing Therapy, Integrated Medical Therapy, and Catheter AbLation for Atrial Fibrillation in Heart Failure Trial

NCT ID: NCT07238452

Last Updated: 2025-11-28

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 1056 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-01
• Study Completion Date: 2033-01-01

Brief Summary

Atrial Fibrillation (AF) and Heart Failure (HF) are colliding global cardiovascular epidemics, individually impairing quality of life and cardiac performance, as well as increasing the risk of hospitalisation and mortality. When AF and HF co-exist, disease progression accelerates and the adverse outcomes are magnified, leading to incrementally higher morbidity, mortality, and healthcare expenditure. The management of AF has been dichotomised into the restoration and maintenance of sinus rhythm ("Rhythm control") or acceptance of AF with control of the ventricular response ("Rate control"). Previous studies suggested that pharmacologic rhythm control and pharmacologic rate control confer similar survival and morbidity outcomes in patients with significant left ventricular dysfunction. Recognising the limitations of pharmacotherapy, more recent studies have examined the utility of catheter ablation procedures, either designed to restore and maintain sinus rhythm (e.g., catheter-based pulmonary vein isolation) or control the ventricular response (e.g., pacemaker implantation in combination with catheter ablation of the atrioventricular junction). Compared to pharmacotherapy, these studies have suggested that catheter ablation may provide sustained improvements in quality of life, decreased hospitalisation and, potentially, improved survival for patients with co-existing AF and HF. However, these studies were performed prior to the modern era of quadruple LV enhancing therapy (beta-blocker, an angiotensin receptor-neprilysin inhibitor, mineralocorticoid receptor antagonist, and an SGLT2 inhibitor). The true impact of catheter-based interventions, and thus the optimal management of AF for patients with co-existing HF is not known. The investigators propose a randomised controlled trial to definitively answer the question regarding the optimal invasive treatment of AF in patients with heart failure with reduced ejection fraction (HFrEF - LVEF ≤ 40%).

Conditions

Heart Failure With Reduced Ejection Fraction; Atrial Fibrillation (AF)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Optimal Medical Therapy

Patients randomised to medical rate control will receive evidence-based beta-blockers (extended-release metoprolol succinate, bisoprolol, carvedilol), titrated to achieve a resting heart rate of \<100 bpm during AF, in accordance with contemporary guidelines (Appendix B). In the event of patients not achieving satisfactory symptom or heart rate-control with monotherapy, then these agents may be combined with digoxin (trough target 0.5 and 0.9 ng/ml) or oral amiodarone.

Group Type: ACTIVE_COMPARATOR

Pharmacological Rate Control

Intervention Type: DRUG

Rate

Catheter Ablation with The Goal of Sinus Rhythm Restoration (Pulmonary Vein Isolation)

Patients randomised to invasive rhythm control will undergo a percutaneous catheter ablation procedure using standardised techniques to achieve pulmonary vein isolation. The procedure will be performed with a combined radiofrequency + pulsed-field ablation energy catheter. Circumferential lesions around the veins will be considered complete when spontaneous, associated PV potentials are no longer recorded by the circular catheter (entrance block) and when exit block (dissociated spontaneous PV ectopy, and/or local PV capture without conduction from the pulmonary vein into the left atrium) has been demonstrated.

Group Type: ACTIVE_COMPARATOR

Pulmonary Vein Isolation

Intervention Type: DEVICE

PVI

Catheter Ablation with The Goal of Ventricular Rate Control and Regularization (AVJ Ablation)

Patients randomised to catheter ablation of the AV junction will undergo a percutaneous catheter ablation procedure using standardised techniques to achieve complete AV block. Patients randomised to AVJ ablation will receive a cardiac resynchronisation capable device owing to the risk of pacing induced cardiomyopathy (CRT-D if LVEF ≤35%, CRT-P or CSP with an FDA approved conduction system lead if LVEF 36-40%)

Group Type: ACTIVE_COMPARATOR

Atrioventricular Node Ablation

Intervention Type: PROCEDURE

AVJ

Interventions

Pulmonary Vein Isolation

PVI

Intervention Type: DEVICE

Atrioventricular Node Ablation

AVJ

Intervention Type: PROCEDURE

Pharmacological Rate Control

Rate

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age of 18 years or older on the date of Informed Consent,
• Atrial fibrillation,
• Left ventricular ejection fraction of 40% or less, measured within 6 months of enrollment,
• Receiving stable foundational HF quadruple therapy at maximally tolerated dose,
• BNP ≥ 100 pg/mL (NT-proBNP ≥ 400 pg/ml), measured within 1 month of randomisation.

Exclusion Criteria

• Anticipated life expectancy less than one year from the consent date,
• Continuous atrial fibrillation of >1 year in duration,
• Left atrial anteroposterior diameter > 6 cm, volume > 100 mL, or volume index > 60 mL/m2,
• Previous left atrial ablation or left atrial surgery,
• The presence of a percutaneous left atrial appendage closure device,
• Uncontrolled hypo- or hyperthyroidism,
• Subject known to be pregnant or breast-feeding,
• Contraindication to oral anticoagulation therapy,
• Left atrial myxoma,
• Myocardial infarction or percutaneous coronary intervention within 3-months of consent,
• History of, or anticipated to undergo heart transplant, ventricular assist device insertion, or mitral or tricuspid valve repair or replacement within 3-months of the consent date.

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of British Columbia

OTHER

Sponsor Role: lead

Responsible Party

Jason Andrade

Director, Electrophysiology, Principal Investigator, Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Jason Andrade

Role: CONTACT

jason.andrade@vch.ca

6048755069

Other Identifiers

H24-02147

Identifier Type: -

Identifier Source: org_study_id