Bone formation and inflammation in cardiac valves

Background-For nearly a century, the mechanical failure of calcified heart valves was attributed to a passive degenerative process, Recently, several case reports described bone formation in surgically excised heart valves an d suggested an unexpected process of tissue repair. Methods and Results-We studied the prevalence and pathology of heterotopic ossification in 347 surgically excised heart valves (256 aortic, 91 mitral) in 324 consecutive patients (182 men, 142 women; mean age 68 years) who un derwent cardiac valve replacement surgery between 1994 and 1998, The valves were examined microscopically to determine the prevalence and features of bone formation and remodeling. Two hundred eighty-eight valves (83%) had dy strophic calcification. Mature lamellar bone with hematopoietic elements an d active bone remodeling were present in 36 valves (13%) with dystrophic ca lcification. Endochondral bone formation, similar to that seen in normal fr acture repair, was identified in 4 valves. Microfractures were present in 9 2% of all valves with ossification, Neoangiogenesis was found in all valves with ossification. Bone morphogenetic proteins 2 and 4 (BMP 2/4), potent o steogenic morphogens, were expressed by myofibroblasts and preosteoblasts i n areas adjacent to B- and T-lymphocyte infiltration in valves where ossifi cation was identified, Mast cells were present in calcified and ossified va lves and were especially prominent in atheromatous regions. Conclusions-Heterotopic ossification consisting of mature lamellar bone for mation and active bone remodeling is a relatively common and unexpected fin ding in end-stage valvular heart disease and may be associated with repair of pathological microfractures in calcified cardiac valves.