Bicuspid aortic valve aortopathy: genetics, pathophysiology and medical therapy

Abstract

The association between ascending aortic aneurysm (AA) and bicuspid aortic valve (BAV) has been well established. Different genetic, haemodynamic and cardiovascular risk factors have been implicated in the development and progression of AA. However, to date, definite conclusions cannot be drawn regarding the exact molecular, cellular and haemodynamic mechanisms causing BAV-associated aortopathy. For this study, we performed a thorough electronic systematic review of the literature using MEDLINE (1960-2012) and EMBASE databases. MeSH terms included: 'bicuspid aortic valve and ascending aorta', 'bicommissural aortic valve and aneurysm', 'bicuspid aortopathy', 'bicuspid aortic valve pathophysiology', 'bicuspid aortic valve and genetics' and 'bicuspid aortic valve and treatment'. We aim in this review to discuss the mechanisms, pathophysiology, genetics and modern drug therapy in the context of BAV-associated aortopathy.

Keywords: Aortic aneurysm; Aortopathy; Bicuspid aortic valve; Genetics; Medical therapy.

Figure 1:

Showing different tributaries to the development and progression of aneurysm in BAV disease. Genetic [30, 31] and haemodynamic factors [34] contributing to the weakness of the aortic wall and trigger the increase in MMP release leading to the TGFBR pathway activation and further dilatation [46, 47]. The presence of cardiovascular risk factors may also contribute to the progressive dilatation of the aorta [15, 19]. All the above interact with and are influenced by epigenetic control [50].

Figure 2:

Demonstrating different bicuspid aortic valve (BAV) phenotypes. RCC: right coronary cusp; LCC: left coronary cusp; NCC: non-coronary cusp. Showing in (A) normal TAV, (B) Type I BAV phenotype, (C) Type II BAV phenotype and (D) Type III BAV phenotype.

Figure 3:

Potential therapeutic targets blocking ANG II pathway. Showing how ACEi block both AT1 and AT2 receptors leading to a lesser protective effect compared with AT1 antagonism by losartan, which inhibits TGF-β activation pathway leading to aortic aneurysm.