Introduction: Nearly half of heart failure patients pre-sent with a left ventricular ejection fraction (LVEF) of >50%. Not only that its incidence is increasing, but diagnosing and managing heart failure with preserved ejection fraction (HFpEF) is challenging and requires combining clinical, imagistic and biological elements. Methods: Natriuretic peptides are hormones secreted in response to myocardial stretch, acting via cyclic gu-anosine monophosphate (cGMP) to reduce fibrosis, counteract hypertrophy and promote vasodilatation.

Results: Although their levels increase in HF regardless of LVEF, it seems that HFpEF exhibit lower concen-tration. However, numerous factors may influence them, such as atrial fibrillation, thus interfering with diagnosis. As such, using several biomarkers in HFpEF diagnosis is recommended and combining the results with transthoracic echocardiography is justifiable. Given these diagnostic difficulties, newer molecules emerged, with increased specificity for HFpEF, such as middle-region pro-ANP (MR-proANP). Not only that NPs have diagnostic role, but they can be regarded as a therapeutic target. Augmenting their levels, by either administering recombinant NPs or inhibiting their breakdown (through sacubitril/valsartan), lead to an increase in cGMP and subsequent vasodilatation and decreased hypertrophy and myocardial fibrosis.

Conclusions: The fact that for a given concentration, the relative risk of death remains the same between phenotypes underlines the contribution of unevenly distributed comorbidities between HFrEF and HFpEF. However, despite controversies, they retain their diag-nostic, therapeutic and prognostic role.