Bone Formation and Inflammation in Cardiac Valves

TLDR

For nearly a century, the mechanical failure of calcified heart valves was attributed to a passive degenerative process. The study examined the prevalence and pathology of heterotopic ossification in 347 surgically excised heart valves from 324 patients undergoing valve replacement between 1994 and 1998. Valves were microscopically examined to determine the prevalence and features of bone formation and remodeling. Among 347 valves, 83 % showed dystrophic calcification, 13 % contained mature lamellar bone with active remodeling, and 4 exhibited endochondral bone formation; ossified valves frequently displayed microfractures (92 %), neoangiogenesis, BMP‑2/4 expression by myofibroblasts and preosteoblasts near lymphocyte infiltrates, and mast cells, indicating that heterotopic ossification is common and may represent a repair response to microfractures in calcified valves.

Abstract

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 and suggested an unexpected process of tissue repair.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 underwent 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 dystrophic calcification. Mature lamellar bone with hematopoietic elements and active bone remodeling were present in 36 valves (13%) with dystrophic calcification. Endochondral bone formation, similar to that seen in normal fracture repair, was identified in 4 valves. Microfractures were present in 92% of all valves with ossification. Neoangiogenesis was found in all valves with ossification. Bone morphogenetic proteins 2 and 4 (BMP 2/4), potent osteogenic morphogens, were expressed by myofibroblasts and preosteoblasts in areas adjacent to B- and T-lymphocyte infiltration in valves where ossification was identified. Mast cells were present in calcified and ossified valves and were especially prominent in atheromatous regions.Heterotopic ossification consisting of mature lamellar bone formation and active bone remodeling is a relatively common and unexpected finding in end-stage valvular heart disease and may be associated with repair of pathological microfractures in calcified cardiac valves.