Sex-differences in Echocardiographic Assessment of Aortic Valve in Young Adult LDLr/ApoB/IGF-II Mice

Background: LDLr/ApoB/IGF-II mice are used as a calcific aortic valve disease (CAVD) model. However, normal aortic valve hemodynamics i.e. remotely from CAVD onset and the sex-related differences are poorly known.

Methods And Results: Four groups of mice, intact males (IM, n = 49) and females (IF, n = 50), castrated males (CxM, n = 79) and ovariectomized females (OxF: 73), underwent a Doppler-echocardiography at 12 weeks of age. Gonadectomy was performed at 8 weeks. Aortic valve assessment using effective orifice area (EOA, using the continuity equation) and peak aortic transvalvular velocity (V) was feasible in 89% of the mice with good to excellent reliability (intraclass correlation coefficients ranging from 0.90 to 0.98, p < 0.001). Mean V was 104 ± 17 cm/s and mean EOA was 1.18*10 ± 0.22*10 cm. EOA indexed to body surface area was 1.5 ± 0.3 cm/m. The 95th percentile of Vpeak was 132 cm/s and the 5th percentile of indexed EOA was 1.0 cm/m. Interestingly, IM had the highest V (114 ± 14 cm/s) vs each of the other groups (CxM: 106 ± 19 cm/s, OxF: 97 ± 13 cm/s and IF: 96 ± 12 cm/s, ANOVA and corrected p < 0.001). This was mostly explained by a higher stroke volume (ANOVA and corrected p < 0.001) in IM compared to other groups. There were no major sex-differences in ventricular systolic function parameters.

Conclusion: In LDLr/ApoB/IGF-II CAVD mice model, an aortic EOA <0.8*10 cm (or indexed EOA <1.0cm/m), and a peak aortic valve velocity > 132 cm/s may be proposed as thresholds to define CAVD. Intact male mice appear to have higher velocities.