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

University of British Columbia

Status and phase: Not yet enrolling; Phase 4

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

Treatments: Drug: Pharmacological Rate Control; Device: Pulmonary Vein Isolation; Procedure: Atrioventricular Node Ablation

Study type: Interventional

Funder types: Other

Identifiers

NCT07238452

H24-02147

Details and patient eligibility

About

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%).

Enrollment: 1,056 estimated patients

Sex: All

Ages: 19+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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1,056 participants in 3 patient groups

Optimal Medical Therapy

Active Comparator group

Description:

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.

Treatment:

Drug: Pharmacological Rate Control

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

Active Comparator group

Description:

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.

Treatment:

Device: Pulmonary Vein Isolation

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

Active Comparator group

Description:

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%)

Treatment:

Procedure: Atrioventricular Node Ablation