Atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) are two growing epidemics that will continue to frequently coexist as our population ages. Here, experts from ACC analyse two major trials- AATAC-AF in Heart Failure and CASTLE-AF trial.

Both atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) share a number of risk factors and common pathophysiology involving tissue fibrosis and electrical remodelling. They also synergistically alter the prognosis and treatment of affected individuals, increasing the risk of stroke, heart failure hospitalization, and death. The loss of atrial contraction in AF reduces cardiac output and impairs diastolic filling, resulting in further hemodynamic compromise in patients with heart failure. Moreover, atrial tachyarrhythmias can induce or exacerbate preexisting ventricular dysfunction, and HFrEF by itself promotes left atrial structural and electrical remodelling, thereby increasing the risk of AF.

Maintaining sinus rhythm in patients with AF prevents further hemodynamic deterioration and improves quality of life. Unfortunately, pharmacological rhythm control in patients with AF and HFrEF remains controversial especially in the light of the main results of the AF-CHF (Atrial Fibrillation and Congestive Heart Failure) trial4 and the DIAMOND-CHF (Danish Investigations of Arrhythmia and Mortality on Dofetilide—Congestive Heart Failure) trial, both of which failed to show reduction in mortality compared with rate-control strategy.

Amiodarone and dofetilide were respectively the main antiarrhythmic drugs tested in those trials and remain the only pharmacological options available in patients with HFrEF according to the international guidelines. These drugs face modest efficacy at maintaining sinus rhythm along with high rates of toxic adverse effects and medication intolerance.