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Calcific aortic stenosis: an update

Nature Clinical Practice Cardiovascular Medicine volume 4, pages 254–262 (2007)Cite this article

Abstract

Calcific aortic stenosis in the elderly is the number one cause of surgical valve replacement in the US and Europe. The incidence of calcific aortic stenosis is increasing as the general age of the population increases. For many years, rheumatic heart disease was the main cause of aortic valve disease. Over the last half century, however, there has been a change from a rheumatic etiology to a 'degenerative' mechanism because of the increase in access to health care in developed countries and the increasing age of the population in the US and Europe. For many years 'degenerative' aortic stenosis was thought to be caused by the passive accumulation of calcium on the surface of the aortic valve leaflet. Recent studies have demonstrated, however, that the etiology of aortic valve disease has a similar pathophysiology to that of vascular atherosclerosis, and that the treatment of this disease could be similar to that of chronic vascular atherosclerosis. This Review will discuss our current understanding of the pathophysiology, risk factors, cellular mechanisms, diagnosis and finally, future medical therapies for calcific aortic stenosis.

Key Points

  • Calcific aortic stenosis is the number one indication for surgical valve replacement in the US and Europe

  • Risk factors include male sex, hypertension, elevated levels of LDL cholesterol, and smoking—similar to those for vascular atherosclerosis

  • Calcification is known to cause the development of stenosis in the diseased aortic valves

  • Experimental models have demonstrated the critical features of aortic valve calcification—osteoblast expression, cell proliferation and atherosclerosis—and specific bone-cell phenotypes have been found in calcifying human valves

  • The definitive, but not curative, therapy for calcific aortic stenosis is valve replacement

  • Future insights into the mechanisms of calcification and its progression might indicate lipid-lowering therapy in modifying the rate of progression of stenosis

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Figure 1: Hypercholesterolemic aortic valve disease
Figure 2: A photograph of a heavily calcified aortic valve removed at the time of surgical valve replacement
Figure 3: Potential pathways depicting inflammatory cytokine activation of aortic valve calcification
Figure 4: Light microscopic images showing the Lrp5 bone signaling markers (A) Lrp5, (B) WNT3 and (C) PCNA (indicated by arrows) in three different valvular lesions: control, degenerative mitral valve, and calcified tricuspid and bicuspid aortic valves
Figure 5: Cholesterol-induced aortic valve myofibroblast differentiation
Figure 6: Simultaneous left ventricular and aortic pressures from two separate catheters in a patient with severe aortic stenosis (aortic valve area = 0.4 cm2/m2)

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Author information

Authors and Affiliations

  1. RO Bonow is the Goldberg Distinguished Professor and Chief of the Division of Cardiology at the Northwestern University Feinberg School of Medicine, NM Rajamannan is Assistant Professor and Valve Director for the Bluhm Cardiovascular Institute, Chicago, IL, and SH Rahimtoola is Distinguished Professor of the University of Southern California, Los Angeles, CA, USA.,

    Nalini M Rajamannan, Robert O Bonow & Shahbudin H Rahimtoola

Authors
  1. Nalini M Rajamannan
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  2. Robert O Bonow
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  3. Shahbudin H Rahimtoola
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Corresponding author

Correspondence to Shahbudin H Rahimtoola.

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Competing interests

NM Rajamannan is an inventor on a patent for the medical treatment of valvular heart disease. The Mayo Clinic is the owner of the patent and she does not receive any Royalties from these patents.

RO Bonow is a consultant for Edwards Lifesciences in the development of percutaneous valve replacement and repair devices.

SH Rahimtoola declared he has no competing interests.

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Rajamannan, N., Bonow, R. & Rahimtoola, S. Calcific aortic stenosis: an update. Nat Rev Cardiol 4, 254–262 (2007). https://doi.org/10.1038/ncpcardio0827

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