Heart failure with preserved ejection fraction (HFpEF): pathophysiology, diagnosis, and new therapies

OBJECTIVE: To synthesize up-to-date scientific evidence on the pathophysiology, diagnostic approach, and emerging therapeutic strategies for heart failure with preserved ejection fraction (HFpEF, its acronym in English), with emphasis on recent clinical trials that have changed the treatment paradigm. METHODS: A literature search was conducted systematically in PubMed, Scopus, and the Cochrane Library, focusing on articles published between 2019 and 2025. RESULTS: HFpEF represents the most common type of heart failure worldwide, with more than 32 million cases, while its prevalence is increasing as a result of population aging, together with increases in obesity, arterial hypertension, and type 2 diabetes mellitus. This condition can be characterized by a complex pathophysiological basis, with coronary microvascular inflammation, mitochondrial dysfunction, ventricular stiffness, and adipopathy representing the key components in this regard. However, diagnosis is the main clinical problem, as it involves combining validated algorithms (H2FPEF and HFA-PEFF) and biological markers with echocardiography and, in specific cases, hemodynamic assessment. Regarding treatment, the only drug class with a class I recommendation in the 2023 European guidelines for HFpEF is iSGLT2, while finerenone has recently demonstrated level A evidence for reducing heart failure events. CONCLUSIONS: HFpEF management needs to be personalized, phenotypic, and multimodal.