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

NCT07238452 | Not Yet Recruiting Phase 4 DMC FDA Device

• 1 other identifier: H24-02147
• Study Type: interventional
• Target: 1,056
• Locations: 0 countries
• Sites: N/A

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)

Keywords

Atrial fibrillation; heart failure; cardiomyopathy; catheter ablation; pulsed field ablation; atrioventricular node ablation; conduction system pacing; cardiac resyncronization therapy

Outcome Measures

Primary Outcomes (1)

• Composite of cardiovascular mortality, stroke, and total number of heart failure events

  5 years

Secondary Outcomes (12)

• Composite of ejection fraction, distance on the 6-minute walk test, and QOL score

  1 year

• Time to death from any cause

  5 years

• Time to death from cardiovascular cause

  5 years

• Number of Participants with unplanned emergency department visit or all-cause hospitalisation

  5 years

• Number of Participants with unplanned emergency department visit or hospitalisation for heart failure

  5 years

Study Arms (3)

Optimal Medical Therapy

ACTIVE COMPARATOR

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.

Drug: Pharmacological Rate Control

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

ACTIVE COMPARATOR

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.

Device: Pulmonary Vein Isolation

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

ACTIVE COMPARATOR

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%)

Procedure: Atrioventricular Node Ablation

Interventions

Pulmonary Vein Isolation DEVICE

PVI

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

Atrioventricular Node Ablation PROCEDURE

AVJ

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

Pharmacological Rate Control DRUG

Rate

Optimal Medical Therapy

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of British Columbia: lead

MeSH Terms

Conditions

Atrial Fibrillation; Heart Failure; Cardiomyopathies

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Jason Andrade

CONTACT

6048755069; jason.andrade@vch.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Electrophysiology, Principal Investigator, Clinical Professor

Study Record Dates

• First Submitted: May 27, 2025
• First Posted: November 20, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): December 1, 2032
• Study Completion (Estimated): January 1, 2033
• Last Updated: November 28, 2025

Record last verified: 2025-11