Strain-based characterization of atrioventricular and left atrial remodelling in rat models of heart failure with preserved ejection fraction.

Abstract

Current experimental models of heart failure with preserved ejection fraction (HFpEF) lack standardized approaches for evaluating left atrial (LA) remodelling and atrioventricular (AV) coupling, leaving a critical gap in mechanistic understanding and phenotypic characterization. This study aimed to explore LA function and AV coupling status in a rat model of hypertension-related HFpEF, thereby providing support for phenotype-specific therapeutic strategies. We established two experimental rat models: A dual-hit model (high-fat diet combined with N-nitro-l-arginine methyl ester; HD + NAME) and a high-salt-sensitive model (Dahl salt-sensitive; Dahl/SS). LA function and AV coupling were quantified using speckle-tracking echocardiography (STE) with a modified LA imaging protocol and dedicated strain analysis software. Key parameters included phasic LA function, circumferential strain rates, LA stiffness index (LASI), and LA reservoir strain (LASr). Correlations with histopathological alterations were also examined. Both HFpEF groups exhibited significant left ventricular remodelling, diastolic dysfunction and reduced LASr compared with control (Control: 25.5&#xa0;&#xb1;&#xa0;3.4%, Dahl/SS: 17.8&#xa0;&#xb1;&#xa0;2.6%, and HD + NAME: 15.6&#xa0;&#xb1;&#xa0;2.9%; all P&#xa0;<&#xa0;0.001 vs. Control). The HD + NAME model demonstrated higher LASI and E/early diastolic circumferential strain rate, indicating impaired AV coupling. Histological analysis revealed LA cardiomyocyte hypertrophy and interstitial fibrosis (fibrotic area: Control: 1.1&#xa0;&#xb1;&#xa0;0.5%; HD + NAME: 4.9&#xa0;&#xb1;&#xa0;1.7%, Dahl/SS: 6.7&#xa0;&#xb1;&#xa0;1.9%; all P&#xa0;<&#xa0;0.001 vs. Control). Importantly, LASI correlated strongly with cardiomyocyte hypertrophy (r&#xa0;=&#xa0;0.0.635) and fibrosis (r&#xa0;=&#xa0;0.733; all P&#xa0;<&#xa0;0.001). Standardized STE enables high-resolution quantification of LA function and AV coupling in preclinical HFpEF models. Comparative evaluation of dual-hit and salt-sensitive hypertension models provides phenotypic stratification and yields novel mechanistic insights into atrioventricular decoupling in HFpEF.