Unicommissural aortic valves: Gross, histological, and immunohistochemical analysis of 52 cases (1978-2008)

Background: Unicommissural aortic valves (UAVs) are rare anomalies in which adjacent cusps of two commissures are congenitally fused. Currently, features of UAVs are poorly characterized. Methods: Fifty-two surgical and autopsy cases of UAV at Mayo Clinic were evaluated for various clinicopathologic features. Histology and immunohistochemistry (IHC) were used in 30 UAVs to identify biomarkers important to developing aortic stenosis. Results: In 52 UAV patients (58% were male, 42% were female), their ages ranged from 18 weeks' gestation to 80 years (mean, 28 years). Functional status was pure stenosis in 20, pure regurgitation in 9, combined in 22, and normal in 1. Common additional cardiovascular disorders included left ventricular hypertrophy (56%) and ascending aortopathies (42%). The position of the true commissure was determined in 30 UAVs and was left posterior in 73%. Gross calcification increased exponentially with age, starting as early as 16 years. Microscopically, the values of the 3 youngest patients showed dysplasia. Other UAVs exhibited fibrous thickening (93%), ventricular pads (89%), aortic pads (81%), and thickened spongy layer (74%). Macrophages were the most common leukocyte by IHC. Bone morphogenetic protein-2 was positive in 27 IHC cases; osteopontin was positive in 15, and matrix metalloproteinase (MMP) 2, MMP-9, and MMP-14 were positive in 1, 6, and 4 cases, respectively. Conclusion: The functional status of UAVs typically involves stenosis but can vary in type and degree or rarely be normal. In early stenosis (<16 years), the pathology is primarily fibrosis with minimal calcification. UAVs show more calcification compared with age-matched bicuspid or tricuspid aortic valves. The molecular mechanisms of calcification and fibrosis in UAVs remain incompletely understood.