Optimising Pacing Therapy, Integrated Medical Therapy, and Catheter AbLation for Atrial Fibrillation in Heart Failure Trial (OPTIMAL AF-HF)

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%).

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure With Reduced Ejection Fraction; Atrial Fibrillation (AF)
• Intervention / Treatment: Drug: Pharmacological Rate Control; Device: Pulmonary Vein Isolation; Procedure: Atrioventricular Node Ablation

• Study Type: Interventional
• Enrollment (Estimated): 1056
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jason Andrade; Phone Number: 6048755069; Email: jason.andrade@vch.ca

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: Pharmacological Rate Control; Rate
Active Comparator: 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.	Device: Pulmonary Vein Isolation; PVI
Active Comparator: 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%)	Procedure: Atrioventricular Node Ablation; AVJ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite of cardiovascular mortality, stroke, and total number of heart failure events	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Number of Participants with unplanned emergency department visit or hospitalisation for atrial fibrillation or arrhythmia	5 years
Number of Participants with heart failure event	5 years
Change in Quality of Life from baseline	5 years
Number of Participants with ischemic stroke or systemic arterial emboli	5 years
Number of Participants with new onset cognitive dysfunction	5 years
Change in left ventricular function (ejection fraction)	5 years
Time to first appropriate and inappropriate ICD intervention (ATP or ICD shock)	5 years

Collaborators and Investigators

• Sponsor: University of British Columbia

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): December 1, 2032
• Study Completion (Estimated): January 1, 2033

Study Registration Dates

• First Submitted: May 27, 2025
• First Submitted That Met QC Criteria: November 17, 2025
• First Posted (Estimated): November 20, 2025

Study Record Updates

• Last Update Posted (Actual): November 28, 2025
• Last Update Submitted That Met QC Criteria: November 21, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Atrial fibrillation; heart failure; catheter ablation; cardiomyopathy; conduction system pacing; pulsed field ablation; atrioventricular node ablation; cardiac resyncronization therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Pathological Conditions, Signs and Symptoms; Heart Failure; Atrial Fibrillation; Cardiomyopathies
• Other Study ID Numbers: H24-02147

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The decision to share IPD will be decided at a later dat by the academic steering committee.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes