Why the study?
A head-to-head comparison of LV morphological and functional changes had never been performed in males and females with severe aortic regurgitation using the latest echocardiography imaging modalities.
Does severe aortic regurgitation cause sexually dimorphic left ventricular remodeling in a rat model?
Does severe aortic regurgitation cause sexually dimorphic left ventricular remodeling in a rat model?
Absolute Event Rate: 157% vs 88%
Female rats with severe aortic regurgitation develop more pronounced left ventricular dilation, quicker wall thickening, and earlier loss of circumferential strain compared to males, highlighting significant sex dimorphism in volume overload remodeling.
Hypothesis-generating for sex-specific LV remodeling in AR; human studies needed before clinical consideration.
BACKGROUND: Aortic valve regurgitation (AR) results in left ventricle (LV) volume overload (VO) leading to its dilation and hypertrophy (H). We study a rat model of severe AR induced by puncturing one or two leaflets using a catheter. Most of our studies were conducted in male animals. Recently, we started investigating if sex dimorphism existed in the AR rat model. We observed that AR females developed as much LVH as males but morphological remodeling differences were present. A head-to-head comparison of LV morphological and functional changes had never been performed in AR males (M) and females (F) using the latest modalities in cardiac imaging by echocardiography. METHODS: We performed a longitudinal study to evaluate the development of LV hypertrophy caused by chronic AR in male and female rats over 6 months. Sham-operated (sham) animals were used as controls. RESULTS: LV diastolic volumes (EDV) increased more over 6 months in sham males than in females (38% vs. 23% for EDV, both p < 0.01). AR resulted in significant LV dilation for both sexes (54% vs. 51% increase in EDV) vs. baseline values. Since normal cardiac growth was less in females, dilation from AR was relatively more important for them (88% (M) vs. 157% (F) increase in EDV over sham). AR caused LV wall thickening in both males and females. It happened sooner for AR females and was more important than in males (25% (M) vs. 56% (F) increase in septum thickness at 2 months and 10% (M) vs. 30% (F) at 6 months). We then evaluated if AR was associated with changes in LV strain using speckle-tracking 2D echocardiography. Global longitudinal strain remained similar between AR and sham animals. Circumferential strain was negatively modulated by AR but only in females and early after VO induction (13% (M) vs. 26% (F)). CONCLUSION: AR resulted in more LV dilation and quicker wall thickening in female AR rats compared to males. Global circumferential strain was negatively modulated in AR females but not in males. AR also seemed to lead to a more spherical LV shape in females whereas; it kept mostly an ellipsoid shape in males. This can influence validity of mass estimation of the dilated LV in females by echocardiography.
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Walsh‐Wilkinson et al. (2020) studied Aortic valve regurgitation (AR) with left ventricle volume overload (n=44). Severe aortic valve regurgitation (AR) induced by leaflet puncture vs. Sham operation was evaluated on Increase in left ventricular end-diastolic volume (EDV) over sham.
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