HFpEF (heart failure with preserved ejection fraction) is a complex and heterogeneous clinical syndrome characterized by impaired ventricular filling and diastolic dysfunction despite preserved ejection fraction. Its pathophysiology is driven by systemic comorbidities – including obesity, hypertension, and diabetes mellitus – and chronic low-grade inflammation. HFpEF represents a major and rapidly growing global health burden, accounting for approximately half of all heart failure cases worldwide. It is associated with high morbidity and mortality, and to date, no definitive disease-modifying therapy has been established.

In this lecture, we will present our experience and key findings obtained using a murine double-hit model combining a high-fat diet (HFD) with L-NAME, a nitric oxide synthase inhibitor. This approach integrates metabolic stress induced by HFD with hypertensive stress resulting from nitric oxide synthase inhibition. The model has been proposed to recapitulate the principal systemic and cardiovascular features of HFpEF and is widely regarded as a translationally relevant experimental platform. However, is this model truly suitable for studying HFpEF?

Contact at IPHYS: Markéta Hlaváčková, Laboratory of Developmental Cardiology, marketa.hlavackova@fgu.cas.cz