Heart Failure with Preserved Ejection Fraction: Clinical Unmet Need

David Sim
National Heart Centre Singapore


Heart Failure is a disease of epidemic proportions. The impact of this new epidemic poses a significant burden on the patients and the society. Many novel therapeutic approaches have emerged and are continuing to evolve, with many exciting possibilities for the future. But with existing contemporary pharmacological therapy for heart failure, prognosis is still fairly poor.

Whereas heart failure was previously synonymous with pump failure (so-called “systolic heart failure”), it is now known that heart failure can occur in the presence of normal pump function or preserved left ventricular (LV) ejection fraction—the syndrome of “heart failure with preserved ejection fraction (HFPEF)”, also popularly called “diastolic heart failure.”

In fact, epidemiologic studies have shown that HFPEF comprises half of all heart failure cases. Compared to heart failure with reduced ejection fraction (HFREF), the overall survival in HFPEF may be better, however in patients following hospitalization for heart failure, the reported outcomes in HFPEF in terms of mortality and rehospitalization rates are similarly poor.

Yet in sharp contrast to the wealth of proven therapies for heart failure with HFREF, trials of conventional heart failure medications have been inconclusive in HFPEF and there is, to date, no therapy proven to reduce mortality in HFPEF. A greater understanding of the distinct pathophysiologic processes in HFPEF is key for the development of novel therapeutic approaches.

Long-term management of HFPEF focuses on the management of a specific cause (hypertension, diabetes, myocardial ischemia), modification of factors that affect the diastolic function (heart rate, blood pressure, circulating blood volume), and symptom reduction.

With better understanding of the pathophysiology of HFPEF, novel treatment strategies are emerging. Among these are agents that enhance cellular cyclic guanosine monophosphate signaling such as soluble guanylate cyclase stimulators, mineralocorticoid receptor antagonists , angiotensin receptor neprilysin inhibitors, and sodium glucose cotransporter type 2 inhibitors.