Optimal PharmacoTherapy and Invasive Management of Atrial Fibrillation in Patients With Heart Failure

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 is 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 designed to restore and maintain sinus rhythm (e.g., catheter-based pulmonary vein isolation). Studies have suggested that catheter ablation procedures may provide sustained improvements in quality of life, decreased hospitalisation and, potentially, improved survival for patients with co-existing AF and HF, when compared to pharmacotherapy. However, significant limitations in these small trials have limited their impact on clinical practice. We propose a randomised controlled trial to definitively answer the question regarding the optimal treatment of AF in patients with heart failure with reduced ejection fraction (HFrEF), specifically aiming to determine if catheter ablation can reduce death, stroke, and heart failure events.

Inclusion Criteria: 1. Age of 18 years or older on the date of Informed Consent, 2. Atrial fibrillation (paroxysmal, persistent or long-standing persistent) 3. Left Ventricular Ejection Fraction of 40% or less, measured within 6 months of enrollment, 4. Receiving (current/planned uptitration) guideline directed medical therapy for heart failure, 5. Receiving stroke prevention therapy, initiated according to guidelines for treatment of AF Exclusion Criteria: 1. Anticipated life expectancy less than one year from the consent date, 2. Continuous atrial fibrillation of \> 2 years in duration at time of enrollment a. Note: AF duration does not refer to time from index AF diagnosis but the duration of the current AF episode, 3. Previous left atrial ablation or left atrial surgery, 4. Left atrial dimension greater than 6 cm, 5. The presence of a percutaneous left atrial appendage closure device, 6. Uncontrolled hypo- or hyperthyroidism, 7. Subject known to be pregnant or breast-feeding, 8. Contraindication to oral anticoagulation therapy, 9. Left atrial myxoma, 10. Type I myocardial infarction or percutaneous coronary intervention within 1-month of consent, 11. Requirement for dialysis due to terminal renal failure, 12. 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, 13. Participation in another investigational drug or device study