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, Valvulopathy, Hemodynamics, Bicuspid aortic valve, Shear stress

Core tip: The bicuspid aortic valve (BAV) is associated with secondary aortopathy and valvulopathy. However, the root cause of those complications remains controversial. While the genetic etiology has been the most popular historically, advances in cardiovascular imaging, flow characterization and tissue culture methodologies have provided new evidence in support of a hemodynamic origin. The assessment of the respective role of genetic and hemodynamic cues in BAV pathogenesis is critical to the development of improved diagnosis tools and patient-specific modalities. This editorial discusses the different possible etiologies of BAV disease with a particular focus on the most recent evidence for the hemodynamic pathway.