Cell- and molecular-level mechanisms contributing to diastolic dysfunction in HFpEF

Abstract

Heart failure with preserved ejection fraction (HFpEF) is the default diagnosis for patients who have symptoms of heart failure, an ejection fraction >0.5, and evidence of diastolic dysfunction. The clinical condition, which was largely unrecognized 30 years ago, is now a major health problem and currently accounts for 50% of all patients with heart failure. Clinical studies show that patients with HFpEF exhibit increased passive stiffness of the ventricles and a slower rate of pressure decline during diastole. This review discusses some of the cell- and molecular-level mechanisms that contribute to these effects and focuses on data obtained using human samples. Collagen cross linking, modulation of protein kinase G-related pathways, Ca2+ handling, and strain-dependent detachment of cross bridges are highlighted as potential factors that could be modulated to improve ventricular function in patients with HFpEF.