Right ventricular stiffness as a key feature in the ZSF1 model of heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome defined by diastolic dysfunction and limited therapeutic options, with increasing recognition of right ventricular (RV) involvement. Using invasive pressure-volume loop analysis, we assessed biventricular hemodynamics in lean and obese ZSF1 rats, a well-established rodent model of HFpEF. Obese rats exhibited significantly increased RV and left ventricular (LV) chamber stiffness, with a positive correlation between RV and LV stiffness constants, indicating biventricular diastolic dysfunction. RV end-systolic elastance was preserved, whereas LV contractility was increased. Despite elevated RV stiffness, myocardial fibrosis was unchanged, while RV and septal cardiomyocyte hypertrophy was significantly increased. These findings demonstrate that RV diastolic dysfunction in this HFpEF model is driven primarily by myocytic stiffening rather than fibrotic remodeling. Our data provide invasive haemodynamic evidence of RV involvement in HFpEF and further support the translational relevance of the ZSF1 rat model for studying biventricular HFpEF pathophysiology.