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Objective: The probability of aortic complications in patients with bicuspid aortic valve is higher in association with aortic regurgitation (AR) compared with aortic stenosis (AS) or normally functioning valves. The objective of this study was to determine whether this is related to the specific characteristics of aneurysmatic dilatation that includes AR or whether AR itself has a negative impact on the aortic wall, independent of aneurysmatic dilatation. Approach and Results: Nondilated aortic specimens were harvested intraoperatively from individuals with tricuspid aortic valves and either AS (n=10) or AR (n=16). For controls, nondilated aortas were harvested during autopsies from individuals with tricuspid aortic valves and no evidence of aortic valve disease (n=10). Histological and immunohistochemical analyses revealed that compared with control aortas, overall medial degeneration was more severe in AR-aortas (P =0.005) but not AS-aortas (P =0.23). This pathological remodeling included mucoid extracellular matrix accumulation (P =0.005), elastin loss (P =0.003), elastin fragmentation (P =0.008), and decreased expression of fibrillin (P =0.003) and collagen (P =0.008). Furthermore, eNOS (endothelial nitric oxide synthase) expression was decreased in the intima (P =0.0008) and in vasa vasorum (P =0.004) of AR-aortas but not AS-aortas (allP &gt;0.05). Likewise, subendothelial apoptosis was increased in AR-aortas (P =0.03) but not AS-aortas (P =0.50).Conclusions: AR has a negative effect on the nondilated ascending aortic wall. Accordingly, our results support the need for more detailed studies of the aortic wall in relation to aortic valve disease and may ultimately lead to more aggressive clinical monitoring and/or surgical criteria for patients with relevant AR. Graphic Abstract: A graphic abstract is available for this article.

Aortic Regurgitation Is Associated With Ascending Aortic Remodeling in the Nondilated Aorta