Abstract 53: Characterization of a Feline HFpEF Model Induced by Slow Progressive Pressure Overload

Abstract

Rationale: The prevalence of Heart Failure with preserved Ejection Fraction (HFpEF) is almost equal to that of Heart Failure with reduced Ejection Fraction (HFrEF) and represents a major public health problem. There are no proven effective treatments for HFpEF, partially attributable to the lack of well-established animal models for HFpEF. Hypothesis: Cats develop a HFpEF phenotype similar to patients after induction of slow progressive pressure overload. Methods and Results: Female and male short hair cats, aged 2 months, underwent either aortic constriction, with a customized pre-shaped band, or sham procedure. In contrast to immediate pressure overload, this approach results in a slow progressive pressure overload during growth. Transthoracic echocardiography was performed at baseline and 1, 2, 3, and 4 months after banding. Concentric LV hypertrophy was observed and heart weight to body weight ratio significantly increased in banded male and female cats compared to sham (male: 8.5±1.6 vs. 4.5±0.4; female: 7.4±0.2 vs. 4.9±0.8; p<0.05). Wet/dry lung weight ratio, indicating pulmonary congestion, did not differ between groups. End-diastolic wall thickness was significantly increased in banded cats at 2, 3 and 4 months, while the end-diastolic diameter and systolic function did not differ between banded and sham cats at any time point. A significant left atrial (LA) enlargement was observed in banded cats at 3 and 4 months, as measured by an increased LA/aorta ratio and increased LA area. LA ejection fraction was significantly decreased after aortic constriction (male sham vs. banded: 75.4±0.2 vs. 47.3±0.2; p<0.01; female sham vs. band: 75.4±2.1 vs. 53.9±4.4; p<0.05). Diastolic function, assessed by tissue Doppler imaging, was impaired in banded cats. Summary and Conclusion: Slow progressive pressure overload in cats induces severe LV concentric hypertrophy, LA enlargement and dysfunction without causing LV dilation or systolic dysfunction, mimicking many clinical phenotypes in HFpEF patients. Further characterization will include incorporating invasive measurements, exercise capacity and serum biomarkers and testing of novel therapies.