Clinical And Pathological Study Of Degenerative Aortic Valvular Disease

Objective:To analysis demographic characteristics, clinical features, risk factors of patients with degenerative aortic valvular disease, in order to provide the theoretical basis for prevention and treatment the disease. And observe the histopathological changes of aortic valve in patients with aortic degenerative stenosis, in order to investigate the related pathogenesis of degenerative aortic valvular disease.Methods:According to the aortic transvalvular peak velocity, patients are divided into mild, moderate and severe aortic stenosis. Record their clinical datas and compare patients’ demographic characteristics and clinical features. Select the age and sex-matched patients, compare the cardiovascular risk factors with severe aortic stenosis patients. And analysis the effect of aortic valve replacement. Collect normal and calcific aortic valves. HE staining, EVG staining, AB-PAS staining, Masson staining, immunohistochemistry and electron microscopy examination were used to observe the histological features of degenerative aortic valves, in order to understand the related pathogenesis of degenerative aortic valvuar desease.Results:Univariate analysis of variance, compared with severe aortic stenosis patients, left ventricular end-diastolic diameter in patients with stenosis combined regurgitation is larger (P<0.001); Compared the left ventricular wall thickness of both interventricular septal and posterior left ventricular wall, that of in severe aortic stenosis patients are thicker than that of in mild, moderate stenosis patients (P<0.001, P=0.012; P<0.001, P=0.021, respectively). BNP levels in severe stenosis patients are significantly higher than in mild stenosis patients (P=0.006). Aortic transvalvular peak pressure is correlated to the interventricular septal thickness, posterior left ventricular wall thickness and BNP level (r=0.637, P<0.001; r=0.603, P<0.001; r=0.490, P=0.001. respectively). According to posterior left ventricular wall thickness and BNP level, we can calculate the aortic transvalvular peak pressure, the regression equation is Y=-97.347+11.127X1+0.031X2[Y=aortic transvalvular peak pressure (mmHg), X1=posterior left ventricular wall thickness (mm), X2=BNP level (pg/ml)]. Compared with age and sex-matched general population, history of smoking and history of hypertension in severe aortic stenosis are higher (P=0.043, P=0.021. respectively), and cholesterol level is higher (P=0.049). The effect of aortic valve replacement is good and the mortality less than1%. Macroscopic observation is that calcific aortic leaflet is thick. Calcification appears in the aortic side of valve leaflets. Inflammatory infiltrate, angiogenesis, cholesterol crystals and foamy cell aggregation can be seen in subendocardial space of the leaflet through the optical microscop. Hyalinization and cartilage-like cells can be seen in the center of fibrosis hyperplasia. Calcification is prevalent in degenerative aortic valves. Compared with normal valve, collagen/elastic fibers in calcified areas and non-calcified areas of stenotic aortic valves are significantly increased (P<0.001, P=0.01, respectively), and collagen content (collagen area/valve area) is also increased (P=0.028, P<0.001, respectively). Compared with normal valve, VEGF expression in non-calcified areas and calcified areas are both increased (P=0.020, P=0.014, respectively). MMP-2expression in calcified areas is significantly higher than in normal valve (P=0.003). Compared with normal valve, MMP-9expression in non-calcified areas and calcified areas are both increased (P=0.023, P<0.001, respectively). TIMP-1expression in calcified areas of stenosic valve is higher than in normal valve (P=0.042). There are no OSX and NFATcl expression in normal valve. The expression of OSX and NFATcl in calcified areas are higher than in non-calcified areas (P=0.040, P=0.025, respectively). Compared with normal valve, TGF-β1expression in non-calcified areas and calcified areas are both significent increased (P=0.016, P=0.018, respectively). Fibroblasts apoptosis and deposition of hydroxyapatite can be observed in the degenerative aortic valve through electron microscope.Conclusion:Aortic transvalvular peak pressure is correlated to the interventricular septal thickness, posterior left ventricular wall thickness and BNP level. According to posterior left ventricular wall thickness and BNP level, we can calculate the aortic transvalvular peak pressure, the regression equation is Y=-97.347+11.127X1+0.031X2[Y=aortic transvalvular peak pressure (mmHg), X1=posterior left ventricular wall thickness (mm), X2=BNP level (pg/ml)]. History of smoking and hypertension and hypercholesterolemia may be risk factors of degenerative aortic valvular disease. The effect of aortic valve replacement is good and the mortality is low. Inflammatory infiltrate, lipid deposition, angiogenesis, extracellular matrix remodeling, ossification are involved in the degenerative calcific aortic stenosis. Apoptosis and calcification may promote each other. Necrosis and apoptosis may be involved in the calcium nodule formation and expansion.