2/2 Catheter Ablation Versus Antiarrhythmic and Heart Failure Drug Therapy in Preserved Ejection Fraction Heart Failure (CABANA-HF)

About This Grant

Atrial fibrillation (AF) often coexists with heart failure with preserved ejection fraction (HFpEF), and when present in combination portends a worse prognosis. HFpEF and AF are closely related as they share left atrial (LA) dysfunction as a common pathophysiologic risk factor. Furthermore, AF is a risk factor for HFpEF; and HFpEF is a risk factor for AF. The presence of AF in HFpEF is also a marker of LA myopathy, which contributes to pulmonary venous congestion, pulmonary vascular disease, right heart failure, cardiorenal syndrome, HF hospitalization, and death. Patients with HFpEF and LA myopathy also cannot appropriately augment stroke volume during exertion, resulting in dependence on increases in heart rate to augment cardiac output. Thus, a rate control strategy for AF in HFpEF may be detrimental and can lead to worse symptoms and exercise tolerance. Despite all that is known about comorbid HFpEF and AF, optimal treatment of AF, including ideal indications and timing of ablation of AF, in HFpEF remains unclear. There are approximately 1.2 million patients with HFpEF and AF in the US. Over the next decade, the prevalence of HFpEF with AF is projected to increase by around 50% due to the aging of the population and the increasing prevalence of key risk factors. Currently, less than 5% of patients with HFpEF and AF receive catheter ablation for atrial fibrillation, mostly for symptom control. An appropriately powered and rigorous randomized clinical trial of AF ablation in HFpEF is therefore a critical unmet need. We propose the Catheter Ablation Versus Antiarrhythmic and Heart Failure Drug Therapy in Preserved Ejection Fraction Heart Failure (CABANA-HF) Trial, a 1552-patient multi-center, randomized, two-arm, open label trial designed to test whether catheter ablation for AF in HFpEF added to guideline- directed medical therapy (GDMT) improves prognosis relative to GDMT alone. The CABANA-HF research proposal consists of two linked grant applications: The Clinical Coordinating Center (CCC) and the Data Coordinating Center (DCC). This application is for the DCC. The primary aim of the trial will be to determine whether routine percutaneous left atrial catheter ablation is superior to optimal guideline-directed medical therapy (GDMT) alone. The primary endpoint will be the composite of cardiovascular (CV) mortality or a worsening HF event. A blinded (to treatment assignment) independent Clinical Events Committee will review and classify all primary and major clinical secondary events. Major secondary endpoints of the trial will include all-cause mortality, all-cause mortality or worsening HF events, time to recurrent AF, quality of life, and incremental cost effectiveness. The concern of increasing morbidity and mortality in HFpEF patients with AF, along with limitations in results of past studies and promising preliminary data, provides a sufficient incentive to undertake this trial with an anticipated high likelihood of guideline-changing results from the CABANA-HF trial.