**3. Embryonic origin of the bicuspid aortic valve: Impact on clinical manifestations of AscAA**

BAV is the most common congenital malformation of the heart, with a prevalence of 1–2% in the general population [23]. It is characterized by the occurrence of two, as

#### *Ascending Aortic Aneurysm in Relation to Aortic Valve Phenotype DOI: http://dx.doi.org/10.5772/intechopen.112883*

opposed to the normal three, aortic valvular cusps, and its morphotype may be classified by the number of raphe – a fusion of the lanulae valvarum of the left-coronary (L), the right-coronary (R) or the noncoronary cusp (N) [24]. A fusion of two cusps, confers a type-I BAV where the most common variant is fusion of the R and L cusps, followed by R–N and L–N. A type II BAV entails fusion of two raphe, and type 0 BAV represents a BAV with only two valvular sinus. Interestlingly, studies investigating the involvement of cardiac progenitor cells in the development of different BAV phenotypes have suggested that the type 1 BAV fusions R–L and R–N (i.e., the most common BAV phenotypes) have separate developmental aberrations. In particular, the R–L fusion was shown to be associated with abnormal behavior of neural crest cells [15], whereas an eNOS mutation has been proposed as a cause for the R–N fusion and a predisposition to aortic dilatation and dissection [25, 26]. The latter finding may suggest a role of second heart field in the development of type 1 R–N BAV as eNOS is expressed by endocardial cells, cardiomyocytes, and VSMCs, all of which are derived from the second heart field [27].

A possible consequence of different cardiac progenitor cells conferring different BAV phenotypes could be that specific regions of the ascending aorta are affected depending on the individual's phenotype. Indeed, we and others have shown an association between BAV phenotype and different clinical manifestations [27, 28]. Furthermore, the R–L phenotype was associated with larger aortic root dimensions, which has been well-documented in echocardiography cohorts [29–32]. Additionally, patients with type 0 BAV tended to present clinically at an earlier age than those with other phenotypes, and a similar trend was observed in men in this study [28]. Interestingly there are trends showing that R–L and type 0 phenotypes are associated with a higher prevalence of ascending aortic dilatation at any segment compared with the R–N phenotype, which relation to aortopathy has historically been conflictingly [28]. For instance, a large study on a surgical cohort reported a lack of ascending aortic root dilatation in combination with R–N phenotype [33].
