Etiology of bicuspid aortic valve disease: Focus on hemodynamics

Abstract

The bicuspid aortic valve (BAV) is the most common form of inheritable cardiac defect. Although this abnormality may still achieve normal valvular function, it is often associated with secondary valvular and aortic complications such as calcific aortic valve disease and aortic dilation. The clinical significance and economic burden of BAV disease justify the need for improved clinical guidelines and more robust therapeutic modalities, which address the root-cause of those pathologies. Unfortunately, the etiology of BAV valvulopathy and aortopathy is still a debated issue. While the BAV anatomy and its secondary complications have been linked historically to a common genetic root, recent advances in medical imaging have demonstrated the existence of altered hemodynamics near BAV leaflets prone to calcification and BAV aortic regions vulnerable to dilation. The abnormal mechanical stresses imposed by the BAV on its leaflets and on the aortic wall could be transduced into cell-mediated processes, leading ultimately to valvular calcification and aortic medial degeneration. Despite increasing evidence for this hemodynamic etiology, the demonstration of the involvement of mechanical abnormalities in the pathogenesis of BAV disease requires the investigation of causality between the blood flow environment imposed on the leaflets and the aortic wall and the local biology, which has been lacking to date. This editorial discusses the different hypothetical etiologies of BAV disease with a particular focus on the most recent advances in cardiovascular imaging, flow characterization techniques and tissue culture methodologies that have provided new evidence in support of the hemodynamic theory.

Keywords: Aortopathy; Bicuspid aortic valve; Hemodynamics; Shear stress; Valvulopathy.

Figure 1

Hemodynamic theory of bicuspid aortic valve disease. The hemodynamic theory of bicuspid aortic valve (BAV) disease can be illustrated as an irreversible feedback loop in which the BAV anatomy would subject the valve leaflets and the ascending aortic wall to local stress overloads. Those stress abnormalities could be sensed by specific endothelial receptors and then transduced into different biological responses that would lead ultimately to the formation of calcific lesions on the leaflets or to the progressive degeneration of the aortic media.