Abstract 420: Characterization of Dahl Salt-Sensitive Rat Model for Heart Failure with Preserved Ejection Fraction Research: Defining Diagnostic Criteria

Abstract

Heart failure with preserved ejection fraction (HFpEF) is a condition that accounts for approximately 50 % of heart failure cases with the prevalence increased with advancing age. As of now, no effective treatment is available for HFpEF, which calls for continued efforts towards novel therapies. Dahl salt-sensitive (Dahl SS) rats have recently been reported as an experimental model of HFpEF, although a specific diagnostic criteria for HFpEF is still unclear in rodents. We aimed to provide clear criteria to identify HFpEF in Dahl SS rats. After a follow-up of 28 weeks, adult female Dahl SS rats receiving high salt (HS, 8 % NaCl) diet developed chronic hypertension (209 ± 80 vs. 147 ± 55 mm Hg; P <0.05 vs. low salt-fed control group (LS, 0.3 % NaCl) with consistent left ventricle (LV) remodeling compared to LS rats (LV hypertrophy index: 2.62 ± 0.07 vs. 1.79 ± 0.03 mg/mm, and cardiomyocyte cross-sectional area: 497 ± 38.9 vs. 290 ± 8.15 μm 2 , respectively; P < 0.05) and EF > 50 % (67.7 ± 1.5 %). Evidence that HS rats have developed HFpEF was observed only in rats with left atrial dimension (LAD)/body weight (BW), E/A, and E/E’ ratios above the 75 th percentile of the LS group (17.50 mm/kg, 1.53, and 14.25, respectively). In addition, HS rats diagnosed with HFpEF had increased LV end-diastolic pressure and plasma NT-proBNP compared to LS rats (12.8 ± 3.4 vs. 5.8 ± 0.8 mm Hg, and 78.7 ± 18.0 vs. 17.7 ± 3.5 pg/mL, respectively; P < 0.05), while no significant changes in LAD/BW, E/A, E/E’, and plasma NT-proBNP were demonstrated in HS rats not matching the suggested criteria for HFpEF. Distance run was not different between HS and LS groups. Survival rate was 39.9 % in HS compared to 94.7 % in LS rats ( P = 0.0001), with stroke as the main cause of death (69.6 % incidence in HS rats). These results provide the first clear criteria for diagnosis of HFpEF in Dahl SS rats. Our findings have important implications for future preclinical studies aiming to develop novel therapeutic strategies targeting diastolic dysfunction in HFpEF.