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Pisano et al. Vessel Plus 2020;4:33 I http://dx.doi.org/10.20517/2574-1209.2020.21 Page 9 of 13
[61]
In a recent and interesting paper, Wu et al. focused the attention on the longitudinal changes of the TAA.
They measured the ascending aortic length (AAL) from the aortic annulus to the origin of the innominate
artery using CT scan images. Interestingly, an AAL of ≥ 13 cm was associated with almost 5-fold higher
[62]
average of aortic adverse events. In addition, Heuts et al. assessed that measurements of aortic volume
and length have superior diagnostic accuracy compared with the maximal diameter and could improve the
timely identification of patients at risk for TAD.

However, we are aware that to validate our opinion and to confirm the importance of these morphological
parameter for surgical indication, a multicentric study is needed.

Flow abnormalities and shear stress
Finally, other important aspects to consider are flow abnormalities and wall shear stress (WSS) in TAA.
Beside the genetic aspects, hemodynamic factors play a crucial role in TAA onset and progression
through the endothelial dysfunction . Endothelial cells, in fact, line the lumen of blood vessels and they
[63]
are at the interface between hemodynamic forces and vascular wall biology. Endothelial cells transduce
mechanical and biological signals from blood flow into intracellular signals cascades through a process
[64]
called mechanotransduction which leads to inflammation and pathological conditions such as aneurysm
and dissection. The endothelial dysfunction induces a switch in phenotype of smooth muscle cells and
fibroblasts. These cells start to synthesize metalloproteinases and inflammatory pathways involved in the
elastic fragmentation and medial degeneration causing aneurysm and finally dissection.

Several studies have been focused on WSS related to BAV patients with aortopathy. Barker et al. found
[65]
that WSS in the ascending aorta of patients with BAV was significantly elevated compared to healthy
volunteers. Different phenotypes of BAV have been described according the cusps fusion (right-left; non-
coronary left; non-coronary right) associated with different grade of WSS. In particular, BAV with fusion
of the right and non-coronary cusps (non-coronary right phenotype) seems to have to higher WSS and
[66]
a greater risk of TAD . Additionally, it is evident that the WSS distribution is different according the
[67]
BAV phenotype. Mahadevia et al. described elevated WSS in the right-anterior wall of the ascending
aorta for right-left BAV phenotype, and right-posterior wall for non-coronary right BAV phenotype. In
all cases of BAV associated with aortopathy, the WSS is higher at the greater curvature of the ascending
[68]
aorta. Accordingly, Della Corte et al. found that medial degeneration was more severe in this region.
[69]
Furthermore, Guzzardi et al. has shown a direct association between WSS and histological alteration of
the aortic wall in TAA patients. BAV patients undergoing ascending aorta replacement had pre-operative
WSS mapping. In particular, they showed high levels of TGFβ-1, MMP-1, MMP-2, and MMP-3 in high
WSS regions causing severe elastic fiber degeneration and extracellular matrix degradation, two important
[70]
mechanisms underlying TAA progression and TAD onset . This may be the explanation why some
patients with aortic size below current intervention criteria develop acute aortic complications.

CLINICAL PRACTICE
Many different options are available to be used as criteria for determining when to operate on patients with
aortic aneurysm, but it remains to be seen which ones will be most predictive of TAD. The identification of
TAA patients with a high risk of TAD is very difficult in clinical practice. In the evaluation of TAA patient,
we thought that the quantification of the absolute aortic diameter is not enough to decide the optimal
surgical timing. It is necessary to perform specific and multiple evaluations. First of all, the absolute
aortic diameter to anthropometric measurements are needed to calculate the ASI, AHI, and IAAs. At
the same time, it is necessary to perform an imaging analysis of the TAA to identify markers of rupture
and dissection in the aortic root and ascending aorta (e.g., prolapse and asymmetry of sinus of Valsalva,
asymmetric ascending aorta dilatation, aortic-ventricle disjunction, and arising of the epiaortic vessels
from the convexity of the ascending aorta). Yet, it is necessary to evaluate the aortic length and the aortic