Physicochemical characterization of natural and bioprosthetic heart valve calcific deposits: Implications for prevention

This investigation was performed to provide a comprehensive physicochemical characterization of calcific deposits (CDs) that form on human heart valves under various pathological conditions. We examined and characterized CDs associated with aortic stenosis on congenitally bicuspid valves (n = 10), degenerative aortic stenosis on valves with previously normal anatomy (n = 10), and rheumatic aortic (n = 10) and mitral (n = 10) stenosis. Native and deproteinated CDs underwent chemical analysis and structural characterization, whereas deproteinated CDs were measured for thermodynamic solubility. The CDs in valvular heart disease were microcrystalline apatitic products containing substantial amounts of sodium magnesium, carbonate, fluoride, and organic fraction. The properties of natural heart valve CDs were compared with those of previously measured CDs that form on or in heart valve bioprostheses. Compared with bioprosthetic valve CDs, natural valve CDs have a higher ratio of calcium to phosphorus, higher crystallinity, and lower solubility. These differences indicate that natural heart valve CDs appear to comprise a more mature biomineral. If the formation of mature CDs proceeds through transient stages involving unstable precursors then the main strategy for prevention of calcific deterioration of bioprosthetic heart valves would be the development of locally applied long-term inhibitors that both (1) suppress nucleation and growth of more soluble precursors and (2) inhibit subsequent augmentation of less soluble CDs.