Heart failure with preserved ejection fraction: An alternative paradigm to explain the clinical implications of atrial fibrillation

Atrial fibrillation (AF) is associated with exercise intolerance, stroke, and all-cause mortality. However, whether this can be solely attributable to the arrhythmia itself or alternative mechanisms remains controversial. Heart failure with preserved ejection (HFpEF) commonly coexists with AF and may contribute to the poor outcomes associated with AF. Indeed, several invasive hemodynamic studies have confirmed that patients with AF are at increased risk of underlying HFpEF and that the presence of HFpEF may have important prognostic implications in these patients. Mechanistically, AF and HFpEF are closely linked. Both conditions are driven by the presence of common cardiovascular risk factors and are associated with left atrial (LA) myopathy, characterized by mechanical and electrical dysfunction. Progressive worsening of this left atrial (LA) myopathy is associated with both increased AF burden and worsening HFpEF. In addition, there is growing evidence to suggest that worsening LA myopathy is associated with poorer outcomes in both conditions and that reversal of the LA myopathy could improve outcomes. In this review article, we will present the epidemiologic and mechanistic evidence underlying the common coexistence of AF and HFpEF, discuss the importance of a progressive LA myopathy in the pathogenesis of both conditions, and review the evidence from important invasive hemodynamic studies. Finally, we will review the prognostic implications of HFpEF in patients with AF and discuss the relative merits of AF burden reduction vs HFpEF reduction in improving outcomes of patients with AF and HFpEF.