Bicuspid Aortic Valve and Thoracic Aortic Aneurysm: Three Patient Populations, Two Disease Phenotypes, and One Shared Genotype

Figure 4

Cardiovascular phenotypes related to malformations of the aortic valve and thoracic aorta. Trilaminar ECM organization of the normal aortic valve (a,c) is characterized by cusps organized into Fibrosa (F), Spongiosa (S), and Ventricularis (V) layers, while the normal proximal aorta (B,D) is characterized by Adventitia (A), Media (M), and Intima (I) layers. Histopathology of a functional BAV, that is a malformed valve without disease, demonstrates preserved ECM organization and normal morphometrics in both the valve (e) and aorta (f). Similarly, the small bicuspid aortic valve of a patient with hypoplastic left heart syndrome, a severe form of aortic valve malformation, shows normal trilaminar ECM organization and morphometrics (g,h). However, BAV with AVD in a younger patient (I) shows ECM disorganization (black arrowheads), in both the affected valve (i) and the aorta with normal dimensions (j). In an older patient with BAV-TAA, there is advanced AVD characterized by marked valve thickening, ECM disorganization (black arrowheads) and calcification (asterisk) and TAA characterized by subintimal hyperplasia, elastic fiber fragmentation, proteoglycan accumulation (white arrowheads), and adventitial fibrosis (asterisk).