Heart failure with preserved ejection fraction: a clinical dilemma

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.