Low Fitness in Midlife: A Novel Therapeutic Target for Heart Failure with Preserved Ejection Fraction Prevention

Heart failure (HF) with preserved ejection fraction (HFpEF) is common and recalcitrant to any medical therapy, highlighting the need for novel strategies focused on its prevention. Recent studies have shown that low cardiorespiratory fitness (CRF) in middle age identifies a subgroup of individuals at particularly high risk for HF, particularly HFpEF. These findings suggest that low CRF in middle age represents an upstream marker for late-life HFpEF. Furthermore, evidence from recent epidemiological studies suggests that low CRF associated risk for HFpEF appears to be modifiable with improvement in CRF. The primary objective of this review is to provide an overview of the potential mechanisms through which exercise training and improvement in CRF may protect against the transition from a low fit stage to clinical HFpEF among at-risk sedentary, middle-age adults.