Biomechanical Manifestations of Diastolic and Systolic Function in Rats with Heart Failure with Preserved Ejection Fraction

Objective Heart failure(HF)is divided into two types:Heart failure with reduced ejection fraction(HFrEF)and heart failure with preserved ejection fraction(HFpEF).The latter always results in diastolic dysfunction,characterized by changes in mechanical properties.The objective of this study is to build a finite element(FE)model of HFpEF and analyze diastolic and systolic function in rats.Methods Ten Dahl salt-sensitive rats were fed either a low-salt(LS)(n=5)or highsalt(HS)(n=5)diet beginning at 7 weeks of age and scanned by ultrasonic machine at 14 weeks of age.A non-linear FE model of the left ventricle(LV)was built from cardiac echo images at end-diastole and passive material properties of the LV were prescribed using Fung’s transversely isotropic constitutive law.Fiber angles of the endocardium and epicardium were prescribed as 53°°and-52°,respectively,with respect to the circumferential direction and varied linearly through the LV wall.The method developed by Krishnamurthywas used to determine the unloaded geometry to estimate the Fung passive material parameters.LV end-diastolic pressure(EDP)was determined from the measured pressure waves and applied to the endocardium at the unloaded geometry to simulate passive filling.Active material properties of the LV were prescribed using Guccione’s time-varying elastance model and maximum isometric tension was scaled to match the measured peak systolic pressure.The finite element model was then coupled to the Windkessel model,whose parameters were adjusted to the measured hemodynamics.Results Measured LVEDPs of LS and HS rats were 4.9±3.4 mmHg and 13.2±5.4 mmHg(P-0.030 8),respectively.End-diastolic Cauchy stress along the fiber direction for LS rats was significantly lower than for HS rats(0.91±0.60 kPa vs 3.00±0.63 kPa,P=0.001 4)and there was a similar trend in end-diastolic Green Strain along the fiber direction(0.058±0.003 vs 0.072±0.010,P=0.012 8,Figure 1b),as well.There was no distinctive difference between end-systolic Cauchy stress along the fiber direction for LS rats and HS rats(17.2±4.3 kPa vs 17.2±5.5 kPa,P=0.991 9)but end-systolic Green Strain along the fiber direction for LS rats was significantly higher than for HS rats(-0. 108±0.017 vs-0.065±0.024,negative sign represents direction).Conclusions For rats with HFpEF,it is the elevated LVEDP that induces the increase in end-diastolic stress and strain,thereby leading to diastolic dysfunction.Because of the preserved ejection fraction,HFpEF has less effect on systolic function.