Bicuspid aortic valve and aortic dilation: The current understanding

Abstract

Aim: The bicuspid aortic valve (BAV) is one of the most common congenital heart disorders affecting 1–2% of the population. Individuals with a BAV tend to develop ascending aortic dilation, and are believed to be at high risk of aortic rupture and dissection. The association between the BAV and aortic stenosis, aortic regurgitation or infective endocarditis has been previously described, leading to the hypothesis of a common developmental anomaly incorporating both the aortic valve and thoracic aorta, and requires genetic solutions. The present article aims to make a comprehensive review of the possible determinants of this congenital defect entity. Methods: A literature retrieval was made by using the search terms ‘bicuspid aortic valve’ and ‘aortic dilation’ or ‘aortic aneurysm’ in major medical databases, including EMBASE, Cochrane Library, LILACS, MEDLINE and ADOLEC. A total of 496 articles were obtained. Relevant studies in the aetiologies of the BAV on the basis of clinical observations and basic research were selected and analysed. Results: Results from clinical observations have taken a haemodynamically resultant aortic dilation in the presence of a BAV into consideration. The two pathogenetic factors, haemodynamic and genetic, might coexist. Each of them could in turn prevail in different clinical pictures or anatomical forms. The presence of medial degeneration, elastic fragmentation and changes in smooth muscle cells was found to be much more severe in patients with a BAV than in those with a tricuspid aortic valve. Determination of the apoptotic index showed significantly increased numbers of dead smooth muscle cells in aneurysmal sections when compared with the normal aorta. Mean endothelial nitric oxide synthase levels in the endothelial cells of the aortic wall in patients with a BAV were significantly lower compared with those with a tricuspid aortic valve. Of importance are the novel findings of extracellular matrix degradation in terms of matrix metalloproteinase and their inhibitors, as well as mutations of variable genes, including Notch1, NKX2.5, ubiquitin fusion degradation 1-like gene and KCNJ2, that have drawn particular attention in the hope of offering an evolutionary explanation of this disorder. Conclusion: The development of the BAV might have diverse molecular triggers, thus it might be difficult to characterize the inciting events that result in a BAV and aortic wall disorders. Extracellular matrix dysregulation and cell death pathways are regarded as important molecular mechanisms of the aortopathy. Matrix degradation and gene mutations are the preferred hypotheses accounting for the development of this congenital lesion.