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

Campbell KS, Sorrell VL. Cell-and molecular-level mechanisms contributing to diastolic dysfunction in HFpEF. J Appl Physiol 119: 1228-1232, 2015. First published April 24, 2015; doi:10.1152/japplphysiol.01168.2014.-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.