The challenge of defining normality for human mitral and aortic valves: geometrical and compositional analysis

Advances in digital imaging technology and in tools for obtaining detailed quantitation of morphological features have facilitated a new approach to pathological assessment of many tissues, including heart valves. In the present study, we quantitatively examined the tissue geometry and composition of structurally normal mitral and aortic valves removed at autopsy or surgery from patients aged 15-84 years. Through univariate analyses of quantitative variables, we have determined which features change distinctively with age. The anterior mitral valve leaflet (AMV) underwent a statistically significant decrease in area of the valve proper and an increase in the number of superficial tissue accumulations called onlays as the patients aged. For all geometric variables measured in the aortic valve, increases were seen with age, leading to a thicker valve, with enlargement of the valve proper and onlays, and with changes in the number of onlays. The mitral valve proper, composed largely of collagen in younger individuals, showed significant increases in glycosaminoglycans and elastin and a relative decrease in collagen with age. The compositional characteristics of the aortic valve proper were similar to those of the mitral valve, with a dramatic relative increase in elastin and a decrease in collagen with age. Valve onlays, when present, were similar in composition to the valve proper for both valves. Our findings regarding normal valve tissue composition, when taken in the context of geometrical features, and together with evidence of age-related changes in the relative amounts of specific constituents, provide a basis on which to analyze human heart valves affected by various known or putative diseases.