Heart Failure With Preserved Ejection Fraction

A Clinical Dilemma

Michel Komajda; Carolyn S.P. Lam


Eur Heart J. 2014;35(16):1022-1032. 

In This Article

Abstract and Introduction


Heart failure with preserved ejection fraction (HFpEF) is now recognized as a major and growing public health problem worldwide. Yet significant uncertainties still surround its pathophysiology and treatment, leaving clinicians in a dilemma regarding its optimal management. Whether HFpEF and heart failure with reduced ejection fraction (HFrEF) are two distinct entities or two ends of a common spectrum remains a matter of debate. In particular, the lack of benefit observed with renin–angiotensin system blockers has raised questions regarding our understanding of the pathophysiology of HFpEF. New paradigms including a prominent role of co-morbidities, inflammation, endothelial dysfunction, and pro-hypertrophic signalling pathways have been proposed. Recent proof-of-concept trials using a phosphodiesterase inhibitor, a mineralocorticoid receptor antagonist, an angiotensin receptor/neprilysin inhibitor, a soluble guanylate cyclase stimulator, or a sino atria, if current blocker provide important insight for the development of novel therapeutic strategies in HFpEF.


Large epidemiologic studies demonstrated that heart failure (HF) could occur in the presence of a normal LVEF, and patients with so-called HF with preserved ejection fraction (HFpEF) may represent up to half of the HF population.[1] In contrast to heart failure with reduced ejection fraction (HFrEF), outcomes in HFpEF have not improved over the last decades, underscoring our continued lack of effective therapies for this important syndrome.[2,3]

The purpose of this review is to provide a global perspective on HFpEF, to discuss the controversies surrounding the disease syndrome, to analyse the reasons for failure of clinical trials to improve outcomes, and to gain insight from recent proof of concept trials.