Bicuspid Aortic Valve Disease: From Bench to Bedside

Abstract

The bicuspid aortic valve (BAV), which is an aortic valve with two functional leaflets instead of the normal three, is the most common congenital heart valve abnormality accounting for a large number of valve replacements in the United States. Although bicuspid aortic valve disease (BAVD) is more common with age, it is not an inevitable consequence of aging. Tricuspid aortic valve disease (TAVD) (Rajamannan et al. 2003) appears to be an actively regulated disease process that cannot be characterized simply as “senile” or “degenerative.” BAVD covers a spectrum of disease from initial changes in the cell biology of the valve leaflets, through early calcification, tissue remodeling and aortic sclerosis, to outflow obstruction and aortic stenosis (Rajamannan 2011a). The later stages are characterized by fibrotic thickening of the valve leaflets and the formation of new blood vessels and calcium nodules – often including the formation of actual bone – throughout the valve leaflets but concentrated near the aortic surface. Epidemiological studies show that some of the risk factors for BAVD are similar to those for vascular atherosclerosis. Age, gender, and certain clinical factors are all associated with an increased risk of BAVD and TAVD. Clinical risk factors associated with the presence of BAVD include elevated low-density lipoprotein (LDL) cholesterol, but the association is relatively weak in those over 65 years old, the group at greatest risk of progressing to aortic stenosis. Other factors include smoking, hypertension, shorter height, lipoprotein (a) level, metabolic syndrome, type II diabetes, end-stage renal disease (but not mild to moderate renal disease), and imbalances in calcium or phosphate metabolism. However, the factors associated with disease initiation may differ from those that promote disease progression. Although aortic stenosis may occur in individuals with otherwise anatomically normal tricuspid aortic valves, congenital valve abnormalities markedly increase the risk as shown in Fig. 3.1. Nearly half of the individuals with aortic stenosis have a bicuspid aortic valve (BAV).