Accelerated mineralization of prosthetic heart valves

The most common cause of prosthetic heart valve failure is severe regurgita tion due to rupture of one or more valve cusps that have become mineralized and rigid. To assess the role of stress and strain in the mineralization i nitiation, in vitro, reference-grade. essentially lipid-free, glutaraldehyd e-tanned bovine pericardium (developed as a standard reference material for bioprosthetic device testing) was exposed to a supersaturated calcium phos phate solution in a high-speed valve tester. The pericardium was tested as sheets constructed into tricuspid valves and dumbbell-shaped tensile-test specimens. and then tested at 720 cycles/min, for up to 18 million cycles. Mineralization was followed using X-ray photog raphy, energy-dispersive X-ray analysis, field-emission scanning electron m icroscopy, and multiple-attenuated internal reflection infrared spectroscop y. Tensile strength of the tissue was determined using a chemomechanical te sting apparatus, Phosphate-based tissue mineralization, first concentrated superficially in an annular distribution at the valve cusp bases, was followed by minimal di ffuse calcification within the valve cusps. Small crystalline patches also appeared in the tissue compressed by the valve support rings. Mineralizatio n occurred in a distribution similar to that found in clinically explanted prosthetic heart valves. in areas of maximal tensile and compressive stress and maximal strain. Infrared and Tensile test data combine to show that ti ssue fatigue due to cyclic loading most likely caused breakage of collagen cross-links. Exposure of superficial broken cross-link sites, and unmasking of hydroxyproline binding sites, of the tissue collagen are thus implicate d as the main factors in phosphate-radical nucleation events leading to val ve mineralization, overshadowing previously cited contributions from tissue lipids and membranes. Mineralization first occurs at the surface regions s ubjected to the greatest stress and strain, and begins as amorphous phospha te-rich rather than crystalline calcium-rich deposits.