Abstract 3549: Regression of Myocardial Hypertrophy After Aortic Valve Replacement: Faster In Women?
To understand sex differences in cardiac remodelling, we studied myocardial hypertrophy and postoperative regression in women and men with aortic stenosis (AS) undergoing aortic valve replacement (AVR). We analysed sex differences in fibrosis related gene expression in intraoperative biopsies from these patients and assessed the effects of estradiol (E2) on the expression of profibrotic genes in cultured rat cardiac fibroblasts.
Methods: We prospectively studied 92 patients, 53 women and 39 men with isolated AS undergoing AVR by pre- and early postoperative echocardiography. In a subgroup we obtained septal biopsies and analysed matrix gene expression by QPCR with informed consent. In addition, we studied the effect of E2 on collagen and matrix metalloproteinase expression in female and male rat cardiac fibroblasts.
Results: Pre- and postoperative systolic function was similar in both sexes (pre-AVR: EF W: 58 %, M 56 %, ns). Similar percentages of women and men (37 and 38 %, ns) had increased end-diastolic ventricular diameters (LVEDD) based on age and sex corrected normal values. However, women had more frequently increased LV mass and LV hypertrophy (LVH) than men (W: 86%, M 56%, p<0.001). Postoperatively, increased LVEDD persisted in 34 % of men but only in 12% of women (p <0,023). LV mass and prevalence of LVH decreased to a greater extent in women than in men, leading to a similar prevalence of LVH after surgery (W: 45 %, M: 36 %, ns). In the surgical biopsies from the septum, men had significantly higher collagen 1 and 3 and MMP2 gene expression compared with controls and with women. MMP9 was stronger downregulated in women. In isolated rat cardiac fibroblasts, E2 downregulated gene expression of collagen 1 and 3 in female and upregulated it in male cells. In contrast, E2 downregulated MMP2 and MMP9 gene expression in cells from both sexes.
Conclusions: Women may adapt to pressure overload with a more benign form of hypertrophy, characterized by more concentric LVH, less matrix turnover and faster regression. This could be due to regulation of matrix gene expression by estrogen.