The Role of Neprilysin Inhibitors in the Treatment of Heart Failure with Preserved Ejection Fraction

Abstract

Clinical and hemodynamic aggravation of heart failure with preserved ejection fraction (HFpEF) is largely due to progression of left ventricular (LV) diastolic dysfunction. The key role in the normal maintenance of diastolic function is played by a high level of activity of the intracellular signaling axis, cyclic guanosine-monophosphate-protein kinase G, the activity of which is significantly reduced in HFpEF. The activity of this axis can be increased by increasing the bioavailability of natriuretic peptides by blocking the enzyme neutral endopeptidase (neprilisin), which is responsible for the destruction of natriuretic peptides.This review presents experimental and clinical data on the use of neprilysin inhibitors in HFpEF and addresses prospects of this treatment.