Is it time for medical therapy for aortic valve disease?

Abstract

Calcific aortic stenosis is the most common indication for surgical valve replacement. Currently there are no medical therapies approved for the treatment of this disease. This review will summarize the clinical and experimental studies published over the past 5 years that indicate that medical therapy may be an option for this patient population.

Figures

Figure 1. Calcified human aortic valve

Photograph of an aortic valve removed at the time of valve replacement. The arrow indicates bone-like nodules on the aortic surface of the aortic valve. The leaflets also demonstrate increased thickening. Reproduced with permission from the BMJ Publishing Group [28].

Figure 2. Cardiovascular features of a patient with familial hypercholesterolemia

Left circumflex artery and aortic valve demonstrating atheromatous changes along the aortic valve surface. Copyright© 2004, Massachusetts Medical Society. All rights reserved [7].

Figure 3. Angiotensin 1 receptors and apo E in a calcified aortic valve

Demonstrates immunohistochemistry for angiotensin 1 receptors, ACE and apo E, which localize along the surface of the aortic valve leaflet. Reproduced with permission from O'Brien KD, Shavelle DM, Caulfield MTet al. Association of angiotensin converting enzyme with low-density lipoprotein in aortic valvular lesions and in human plasma. Circulation 106(17), 2224–2230 (2002). ACE: Angiotensin converting enzyme; AngII: Angiotensin II; Apo: Apolipoprotein;

Figure 4. Potential mechanism for aortic valve calcification

The cell within the valve develops osteoblast-like features that synthesize bone matrix proteins involved in the calcification process within the valve leaflet. Reproduced with permission from the BMJ Publishing Group [28]. Cbfα: Core binding factor alpha-1; LDL: Low-density lipoprotein; PDGF: Platelet-derived growth factor; TGF: Tissue growth factor.

Figure 5. Experimental hypercholesterolemia and atorvastatin treatment in aortic valves

Demonstrates the effects of elevated cholesterol with and without atorvastatin in rabbit aortic valves. (A1,B1) The normal aortic valve surface is thin and intact, with a smooth endothelial layer in the spongiosa layer of the valve, (C1,D1) and there are no macrophages or proliferation. (A2) On a cholesterol diet, foam cells converge to form a large lipid-laden lesion on the valve leaflet, (C2) collagen is formed, (B2) and is stained blue, (D2) foam cells stain positive for macrophage cells, and there is a marked increase in myofibroblast proliferation cell nuclear antigen staining. (A3–D3) Animals on a cholesterol diet and treated with atorvastatin have a marked decrease in abnormal findings (A2–D2) seen in animals on only the cholesterol diet. Reproduced with permission from Rajamannan NM, Subramaniam M, Springett M et al. Atorvastatin inhibits hypercholesterolemia-induced cellular proliferation and bone matrix production in the rabbit aortic valve. Circulation 105(22), 2260–2265 (2002).

Figure 6. Potential therapeutic approach for aortic valve disease

Demonstrates the signaling pathways important in the treatment of aortic valve disease [38]. ACEI: Angiotensin-converting enzyme inhibitor; AT: Angiotensin; ENOS: Endothelial nitric oxide synthase; LDL: Low-density lipoprotein; NO: Nitric oxide.