Content area
Full text
Figure 1. Two aortic valves observed at autopsy showing progression of calcific aortic stenosis with corresponding radiographs demonstrating calcific deposits. (A) Aortic valve from an 83-year-old female. Note small calcific nodules on aortic surface of cusps with sparing of the free edge. Black line indicates region of sectioning. (B) Histologic section of cusp with small calcific deposits on aortic surface. Boxed inset is magnified in (C) and shows disruption of the zona fibrosa by small coalescing calcific deposits on the aortic surface. (D) Aortic valve from an 82-year-old female. There is marked nodular calcification of the cusps with bulky deposits filling the sinuses. (E) Histologic section through the cusp shows calcific nodules effacing leaflet architecture. Note fibrotic thickening of the ventricular surface.
(Figure omitted. See article PDF.)
Figure 2. Histologic progression of calcific aortic valve disease. (A) Early lesion. Aortic valve cusp showing early atheromatous lesion on aortic surface and fatty change in spongiosa. (B) Higher magnification shows atheromatous changes in fibrosa. (C) Von Kossa stain highlighting microscopic calcifications (calcium stains black). (D) Intermediate lesion showing focal plate-like calcification with satellite calcific deposits seen in (E) . (F) Atheromatous changes with cholesterol clefts near calcific deposits.
(Figure omitted. See article PDF.)
Figure 3. Progression of bicuspid aortic valve calcification. (A) Bicuspid aortic valve viewed from the aortic surface (early lesion); gross specimen and x-ray shows calcification limited to raphe. (B) A bicuspid valve with marked calcification and ulceration of the aortic surface. (C) A bicuspid aortic valve obtained at autopsy from a 49-year-old male who died suddenly (late lesion). (D) Severe nodular calcification arising in a bicuspid valve. Note multiple nodules involving the aortic surface and obscuring the raphe.
(Figure omitted. See article PDF.)
Figure 4. Potential paradigm for the understanding of calcific aortic stenosis. Traditional cardiovascular risk factors promote valvular calcification via atherosclerosis. Myoblast differentiation and proteoglycan synthesis and lipoprotein binding may enhance calcification. Alternatively, transdifferentiation into osteogenic phenotypes through the upregulation of Wnt/β-catenin, RANK/RANKL/OPG, Runx2/Cbfa1 and Msx2 pathways may occur. Systemic and paracrine regulators of osteoblast function, calcium hemostasis and dystrophic epitaxial calcification play an increasing role as calcification progresses. Genetic factors, valve morphology (e.g., unicuspid and bicuspid valves) and shear stress likely contribute to disease progression across the full spectrum of...