Bioprosthetic Heart Valve Calcification: Clinicopathologic Correlations, Mechanisms, and Prevention

Bioprostheses, composed of chemically treated animal tissue and termed heterografts or xenografts, are the most widely used type of substitute heart valve. Their major limitation is structural degeneration caused by calcification. Calcification following implantation occurs in a tissue made vulnerable to calcification by the chemical treatment and physical changes induced during valve fabrication and their consequences following implantation. Data from clinical valve explants and subdermal and circulatory experiments in animal models have elucidated the pathophysiology, earliest events, and determinants of this significant clinical problem. The primary mechanism of calcification appears to result from exposure of a susceptible substrate (with phosphoester-containing devitalized cells and cell fragments) to extracellular fluid rich in calcium. The key drivers are (1) biochemical environment, (2) implant structure and chemistry, both of which are prerequisite to calcification, and (3) mechanical stress, which accelerates site-specific mineralization. Therefore, the primary approaches to inhibiting the fundamental process of calcification target the processes involved in the nucleation of calcific deposits and thus have sought to remove cell-based phospholipids or otherwise alter the substrate.