Metallothionein Link to Bicuspid Aortic Valve–Associated Ascending Aortic Dilatation

Bicuspid aortic valve (BAV) is the most common congenital heart defect, occurring in 1% to 2% of the general population.1 Given the high incidence of sequelae, including aortic valve calcification and dysfunction, congenital aortic malformations, and aortic dilatation and dissection, it may account for considerable morbidity and mortality compared with other congenital cardiac abnormalities. The aortic dilatation that occurs with BAV occurs more frequently and at a younger age than it does in patients with trileaflet aortic valves, and the clinical significance of the correlation between BAV and ascending aortic dilatation is based on the potential for aortic dissection and rupture.2 Defining a potential molecular biological basis for aneurysm formation in BAV is critical for understanding disease progression and designing strategies for intervention. Medical treatments that might mitigate or halt the progression of aneurysmal expansion may significantly decrease the incidence of rupture and death and reduce the number of patients requiring high-risk surgical interventions. Potential targets for medical therapy have only recently begun to be elucidated, and much remains unclear about the mechanism of aneurysm formation and expansion.Article see p 2498 Unfortunately, the precise mechanisms underlying the development and progression of thoracic aortic disease in BAV patients have not been clearly delineated. Two logical considerations are most frequently believed to play a major role in this context: that the increased hemodynamic load placed on the proximal aorta may result in progressive aortic dilatation and that an as-yet unidentified genetic or developmental abnormality in the proximal aortic tissue clinically results in altered integrity of the extracellular matrix with consequent weakness of the aortic wall.Although the first hypothesis has the advantage of relative simplicity, several studies suggest that hemodynamic alterations alone cannot be responsible for aortic dilatation in these patients. In fact, aortic dilatation occurs in the presence …