PHYSICOCHEMICAL CHARACTERIZATION OF NATURAL AND BIOPROSTHETIC HEART-VALVE CALCIFIC DEPOSITS - IMPLICATIONS FOR PREVENTION

This investigation was performed to provide a comprehensive physicoche mical characterization of calcific deposits (CDs) that form on human h eart valves under various pathological conditions. We examined and cha racterized CDs associated with aortic stenosis on congenitally bicuspi d valves (n = 10), degenerative aortic stenosis on valves with previou sly normal anatomy (n = 10), and rheumatic aortic (n = 10) and mitral (n = 10) stenosis. Native and deproteinated CDs underwent chemical ana lysis and structural characterization, whereas deproteinated CDs were measured for thermodynamic solubility. The CDs in valvular heart disea se were microcrystalline apatitic products containing substantial amou nts of sodium, magnesium, carbonate, fluoride, and organic fraction. T he properties of natural heart valve CDs were compared with those of p reviously measured CDs that form on or in heart valve biopxostheses. C ompared with bioprosthetic valve CDs, natural valve CDs have a higher ratio of calcium to phosphorus, higher crystallinity, and lower solubi lity. These differences indicate that natural heart valve CDs appear t o comprise a more mature biomineral. If the formation of mature CDs pr oceeds through transient stages involving unstable precursors, then th e main strategy for prevention of calcific deterioration of bioprosthe tic heart valves would be the development of locally applied long-term inhibitors that both (1) suppress nucleation and growth of more solub le precursors and (2) inhibit subsequent augmentation of less soluble CDs.