Bicuspid Aortic Valve Disease and Ascending Aortic Aneurysms: Gaps in Knowledge

Abstract

The bicuspid aortic valve is the most common congenital cardiac anomaly in developed nations. The abnormal bicuspid morphology of the aortic valve results in valvular dysfunction and subsequent hemodynamic derangements. However, the clinical presentation of bicuspid aortic valve disease remains quite heterogeneous with patients presenting from infancy to late adulthood with variable degrees of valvular stenosis and insufficiency and associated abnormalities including aortic coarctation, hypoplastic left heart structures, and ascending aortic dilatation. Emerging evidence suggests that the heterogeneous presentation of bicuspid aortic valve phenotypes may be a more complex matter related to congenital, genetic, and/or connective tissue abnormalities. Optimal management of patients with BAV disease and associated ascending aortic aneurysms often requires a thoughtful approach, carefully assessing various risk factors of the aortic valve and the aorta and discerning individual indications for ongoing surveillance, medical management, and operative intervention. We review current concepts of anatomic classification, pathophysiology, natural history, and clinical management of bicuspid aortic valve disease with associated ascending aortic aneurysms.

The Association Between Aortic Valve Leaflet Morphology and Patterns of Aortic Dilation in Patients With Bicuspid Aortic Valves

“…Multiple factors are of importance in the formation of the semilunar valves. Several genes or gene products have been implicated in formation of BAV, and some forms of BAV seem to be heritable [2,15]. A mutation in NOTCH-1 has been shown to cause cardiac abnormalities, including BAV with severe calcification [8,14].…”

“…These lesions are similar in fibrillin-1-deficient aorta (Marfan syndrome). Matrix metalloproteinases, endogenous enzymes that degrade matrix components, have been implicated in atherosclerotic aortic aneurysm formation, and matrix metalloproteinases become activated in fibrillin-1-deficient tissues, degrading the structural support of the aorta and resulting in dilation, aneurysms, and dissection [2,15,18]. Fedak and associates [15] found that matrix metalloproteinases activity may be elevated in the aorta of patients with BAV.…”

“…Recognition of these differences may eventually be helpful for patient counseling and the planning of follow-up. congenital heart anomaly in the general population, affecting 1% to 2% of individuals worldwide, and is responsible for more deaths and complications than the combined effects of all the other congenital heart defects [1,2]. Bicuspid aortic valve, which results from abnormal aortic leaflet formation during valvulogenesis, is most likely caused by a complex developmental process rather than the fusion of two normal leaflets [3].…”

Genetics of Thoracic Aortic Aneurysm

“…The main predictor of aortic dissection is the aortic diameter. 19,20 Historically, aortic diameters >5.5 cm are regarded as at high risk for dissection. Aortas with a diameter >6 cm have a 3.6% risk of rupture, and 10.8% of such patients die because of dissection within a year.…”

Part 2 - Sudden Cardiac Death in Athletes Focused Cause-and-Effect Screening

“…An aortic root dimension >40 mm in highly conditioned male athletes and >34 mm in female athletes is uncommon; is unlikely to represent the physiological consequences of exercise training; is most likely an expression of a pathological condition [136]; and mandates size-based surveillance [137] Table 4.Although there are multiple types of aortic aneurysms [137] there are three syndromic aortopathies of particular concern in asymptomatic athletes:Marfan syndrome [138,139],BAV [140][141][142], and cystic medial necrosis [143]. The presence of any aortic valve regurgitation in a young athlete should alert the examiner to a possible structural abnormality of the aortic valve [140].…”