A research team from the Medical University of Vienna has developed a new experimental model that more accurately reflects the complexities of heart failure with preserved ejection fraction (HFpEF) HFpEF is one of the most challenging conditions in cardiology. The findings were presented at the European Society of Cardiology (ESC) Congress 2025.

HFpEF is frequently associated with hypertension, obesity, diabetes, and chronic kidney disease. While its prevalence continues to rise, progress in treatment has been limited, partly due to the lack of a robust translational model. To address this gap, investigators refined a previously published mouse model using a “two-hit” approach: metabolic stress through obesity and diabetes, and hemodynamic stress from continuous d-aldosterone infusion.

The study showed that Leprdb/db mice exposed to both stressors developed characteristic features of HFpEF. These included preserved ejection fraction but reduced cardiac index, left ventricular hypertrophy, and significant diastolic dysfunction as evidenced by elevated E/A and E/e′ ratios. Structural remodeling was marked by enlarged left atrial size, while functional analysis revealed impaired longitudinal strain. Vascular studies revealed reduced endothelial relaxation and heightened vasoconstriction in both renal arteries and the aorta. This highlights systemic vascular involvement. Also, no evidence of right heart failure or pre-capillary pulmonary hypertension was observed.

The researchers conclude that this refined two-hit HFpEF model effectively mirrors diastolic dysfunction, atrial remodeling, vascular impairment, and fibrosis. By better replicating patient pathophysiology, it offers a valuable tool for preclinical testing of future HFpEF therapies.