Osseous Metaplasia in Calcific Aortic Valve Stenosis: Role of Congenital Bicuspid Valves
PA VanderLaan, RF Padera, FJ Schoen, RM Mitchell. Brigham and Women's Hospital, Boston, MA
Background: Calcific aortic valve stenosis (CAVS) is prevalent in aging populations, and is the most common pathology in aortic valves (AVs) requiring surgical excision; the pathogenesis is uncertain and controversial. We correlated the clinical and pathologic characteristics of AVs excised for CAVS that also demonstrate osseous metaplasia (OM).
Design: A retrospective analysis was performed for 2087 native AVs excised for CAVS at Brigham and Women's Hospital from January 2003 to July 2009. Cases of active endocarditis were excluded, as were fragmented valves where cuspal number could not be evaluated; 37 glutaraldehyde-pretreated bioprosthetic AVs excised for calcific degeneration were also examined, implanted from 2-24 years (mean 11.3). Patient demographics were correlated with histologic features (including OM) as diagnosed on paraffin embedded, formalin-fixed, decalcified H&E stained sections.
Results: Among 2087 native AVs with CAVS, 1597 (76%) were tricuspid (TC), 486 (23%) were bicuspid (BC), and 4 (0.2%) were unicuspid, with an overall M:F ratio of roughly 1.5:1. Overall, OM was present in 15% of valves with CAVS. OM was approximately twice as common in BC valves versus TC valves (23.5% vs. 12.6%, Z=5.85), with an earlier mean age of excision (59.7 vs. 75.6 years, p<0.0001). OM was also more common in valves removed from males versus females, in both BC (26.6% vs. 21.7%, Z=2.29), and TC valves (14.3% vs. 10.5%, Z=2.31), with an earlier age of excision (BC: 58.9 vs. 61.6 years, p<0.01; TC: 75.0 vs. 76.3 years, p<0.01). Notably, OM was not observed in any bioprosthetic AVs excised for calcific degeneration.
Conclusions: OM is a common finding in native AVs excised for CAVS, and is more frequent in congenital bicuspid valves. The higher frequency of OM in BC valves with CAVS at an earlier age suggests an inherent susceptibility of these congenitally abnormal valves, possibly attributable to mechanical effects or an intrinsic molecular phenotype of the valve cells. The higher incidence of OM in men further suggests a role for sex hormone modulation of the metaplastic process. The absence of OM in non-viable bioprosthetic AVs suggests osteoblastic transformation of intrinsic cells rather than recruitment of circulating stem cells. These findings can direct future mechanistic studies in unraveling the pathogenesis of CAVS.
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 23, Wednesday Afternoon