Heart failure with preserved ejection fraction

Abstract Heart failure with preserved ejection fraction (HFpEF) is a diverse syndrome characterized by signs and symptoms of heart failure with relatively preserved ejection fraction. Despite the established efficacy of numerous classes of drugs and devices in heart failure with reduced ejection fraction, no specific therapy has yet proven to reduce morbidity and mortality in HFpEF. Currently, treatment of HFpEF remains empiric, and includes diuretic therapy for decongestion, treatment of hypertension, diagnosis and treatment of ischaemia, rate control for atrial fibrillation, and treatment of co-morbidities. While outcomes trials in HFpEF have tested renin–angiotensin–aldosterone inhibitors, and none have met their primary endpoint, there is some evidence that in appropriate patients, the mineralocorticoid receptor antagonist spironolactone may be helpful to reduce heart failure hospitalizations. Several other medications have been tested in phase II trials. Sildenafil, isosorbide mononitrate, and the soluble guanylate cyclase stimulator vericiguat did not show benefit in phase II trials. In contrast, sacubitril/valsartan was associated with a significant decrease in N-terminal pro-B-type natriuretic peptide values and improvement in left atrial size in a phase II trial. A large phase III trial to confirm these findings is under way.