**7. Implications of aortic valve disease on degenerative ascending aortic aneurysm**

There are signs that degenerative AscAA is also associated with aortic valve disease when examining the surgical ASAP-cohort (described in detail elsewhere [12]); BAV-associated aortopathy has an equal prevalence of aortic stenosis (AS) and aortic regurgitation (AI). Contrastingly TAV-associated (degenerative) AscAA often associates with AI but very seldomly AS. This may imply that AS has protective effects on AscAA development, or the inverse, that AscAA patients are protected from AS.

The association of AI with degenerative AscAA may in part represent secondary causes of AI, i.e., disease of surrounding structures [104]. However, AI, combined with degenerative AscAA, was also prevalent in the absence of aortic root dilatation, as seen in the ASAP cohort, pointing toward a primary cause of AI to AscAA formation. Notably, AI is a well-known prognostic factor in clinical outcomes of patients undergoing ascending aortic repair [105]. A worse surgical outcome for AscAA/AI repair is reported in both BAV and TAV individuals [106].

Interestingly, further strengthening the association of AI to AscAA formation is the fact that degenerative changes are noted in ascending aortas of patients with *Ascending Aortic Aneurysm in Relation to Aortic Valve Phenotype DOI: http://dx.doi.org/10.5772/intechopen.112883*

normal aortic diamters and AI. Specifically, elastin fragmentation, thinning and MEMA (indicative of VSMC death) have been observed in patients with AI but not AS [105, 107]. One apparent line of investigation not yet explored is whether this association can be observed in individuals with BAV without dilatation but with respective aortic valve disease [37]. Neither have implications of AI-associated ascending aortic degeneration been investigated as a possible player in AscAA formation.

## **8. Summary**

In summary, the impact of aortic valve cuspidity on ascending aortic aneurysm is well-established. Specifically, BAV aortopathy has been associated with endothelial instability and endothelial-to-mesenchymal transition, possibly of embryonic origin. Moreover, different BAV fusion types may impose different mechanisms of aortopathy, with different aortic segments being affected. TAV-associated degenerative aneurysms, on the other hand, are molecularly more similar to AAA with clear medial degeneration and inflammation. Also, aortic valve disease may play a role in degenerative aneurysm formation, with aortic dilatation occurring almost exclusively in combination with aortic regurgitation. This is further supported by histopathological evidence.

As the aortic valve and ascending aorta are not only anatomically proximate but also embryonically associated and physiologically interacting, the impact of aortic valve cuspidity and disease on ascending aortopathy is warranted further research specifically to explore more patient-specific molecular mechanisms. An elucidation of the molecular underpinnings of AscAA development in different conditions of the aortic valve will help guide novel diagnosis and treatment strategies.
