Systemic inflammatory conditions
Endocardial involvement is relatively common in systemic lupus erythematosus (SLE).7
There may be fusion of the mitral valve commissures leading to stenosis but, more commonly, there is generalised thickening of the leaflets (30–70%) with regurgitation (30–50%). Libman-Sacks vegetations are usually <10 mm in diameter, sessile, of mixed echogenicity and usually rounded. They may occur anywhere – most commonly at the leaflet edges on the atrial surface of the mitral valve and, less frequently, at the ventricular side of the aortic valve. The right-sided valves are rarely affected.
Valve lesions are more common in the presence of antiphospholipid antibodies and may occur in the absence of features of SLE in the antiphospholipid syndrome.
Rheumatoid arthritis causes an immune-complex valvulitis with infiltration of plasma cells, histiocytes, lymphocytes and eosinophils leading to fibrosis and retraction. Nodules 4–12 mm in diameter may develop at the base of the mitral or aortic valves. Occasionally there may be more generalised valvulitis with leaflet fibrosis and retraction causing regurgitation.
Ankylosing spondylitis is associated with HLA-B27 mediated chronic inflammation and proliferative endarteritis of the aortic root and left-sided valves. The frequency of valve disease is uncertain. Aortic valve thickening has been reported in 40%, mitral valve thickening in 34% and significant aortic dilatation in 25%.
Novel treatment strategies
The similarity between atherosclerosis and degenerative aortic valve disease led to trials of targeted treatments in modifying this process. Statins are HMG–CoA reductase inhibitors that reduce low-density lipoprotein and total cholesterol. They have proven efficacy in both primary and secondary prevention of cardiovascular events. However, three randomised control trials (SALTIRE, SEAS and ASTRONOMER) failed to show any benefit of cholesterol lowering therapies on aortic stenosis progression, valvular calcification or composite cardiovascular event endpoints. 8-10
The appreciation that calcification is the key pathological process driving progressive valve narrowing suggests that it should be targeted directly with novel therapies. Indeed this hypothesis is currently being tested in SALTIRE 2, a randomised controlled trial testing whether drugs targeting calcium metabolism can slow disease progression in aortic stenosis (Clinical trials.gov NCT02132026).
Conclusion
Heart valve disease is emerging as an increasing health care burden, yet medical therapies are often lacking. We have reviewed the key pathological processes underlying the most common valvular conditions. Improved understanding of these mechanisms will prove key to the development of novel therapeutic strategies.
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References
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8. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. 352, 2389–2397 (2005).
9. Rossebø, A. B. et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N. Engl. J. Med. 359, 1343–1356 (2008).
10. Chan, K. L. et al. Effect of Lipid Lowering With Rosuvastatin on Progression of Aortic Stenosis Results of the Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) Trial. Circulation 121, 306–U247 (2010).
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