Abstract 14274: Novel Insights into Early Aortic Valve Pathology as a Precursor to Clinical Stenosis
Background: Aortic valve (AV) stenosis (AS) is characterized by a long latent period followed by rapid progression to death after the onset of symptoms where the underlying pathogenesis is poorly understood.
Methods: Grossly normal AV leaflets (n=34) from 18 autopsied hearts (mean age 61 years) and 8 heavily calcified surgical aortic valve explants (n=24 leaflets) were examined. These were assessed on H&E, Movat pentachrome, PAS, picrosirius red, and von Kossa (calcium) stains. Immunohistochemical markers for inflammatory cells (CD68, CD45RO), interstitial cell phenotypes (α-SMA, desmin, and vimentin) and mineralization (bone morphogenic protein-2 [BMP-2], matrix GLa protein [MGP], and osteoprotegerin [OPG]) were all graded semi-quantitatively.
Results: 23 lesion sites were found in leaflets from autopsy where 5 showed only lipid deposits while 18 had both lipid and calcification. Lesions were exclusively found at the site of valve attachment (44%) and/or region proximal to the line of closure (24%). Speckled calcification (particles ≤2 µm) was indentified in 7 lesions whereas 11 had larger particle size. The lesion morphologies were classified as early (proteoglycan + lipid) or late lipid insudation (lipid only) where significant differences were noted for free cholesterol, calcification and associated proteins MGP and OPG (see graph) while all surgical valves showed extensive calcification with inflammatory cells, fibrin, and varying degrees of bone forming proteins.
Conclusions: Lipid insudation of the valve interstitium is the earliest event followed by speckled calcification with minimal inflammation. The accumulation of free cholesterol is accompanied by larger calcified particulate with expression of mineralization markers, consistent with lesion progression. These results raise the possibility of instituting lipid-lowering therapy early for patients at high risk of developing AS.
- © 2011 by American Heart Association, Inc.