Correlation between wall shear stress and wall rupture properties in ascending thoracic aortic aneurysms

Abstract

Introduction Ascending thoracic aorta aneurysm (ATAA) is the 19th common cause of human deaths. Despite important recent progress to better understand the pathogenesis and the development of the disease, the role played by deranged hemodynamics on the ATAAs risk of rupture is still partially unknown (Cheung et al. 2017; Farzaneh et al. 2019). The aim of this study is to obtain crucial indications about this role by combining in vivo, in vitro and in silico analyses (Figure 1). 2. Methods Computational fluid dynamics analyses were performed on 10 patients using patient-specific geometries and boundary conditions derived from 4D MRI. Blood flow time-averaged wall shear stress (TAWSS), helicity and eccentricity descriptors were assessed (Condemi et al 2017). A bulge inflation test was carried out in vitro on the 10 ATAAs after surgical repair (Farzaneh et al. 2019). The biomechanics and rupture properties of these samples were derived: burst pressure, physiological tangent modulus (Ephysio), Cauchy stress at the rupture stage (sigmarup), rupture stretch (lambdarup) and rupture stretch criteria (gammastretch). Spearman's rank-order correlation was performed to determine association between all variables. 3. Results and discussion The results showed a statistically significant (p<0.01) negative correlation between Ephysio and the TAWSS (r=-0.77 and p=0.009). A statistically significant positive correlation was found between sigmarup and the TAWSS (r=0.879 and p=0.001) and between lambdarup and the TAWSS (r=0.867 and p=0.001). Understanding the relationship between hemodynamics descriptors and rupture risk is not a trivial issue and there is still a pressing need to conduct research on their possible correlation for potential application in clinical prognosis. Chooi et al. (2016) showed that low residence time reduces the water flux and the advection of macromolecules into and across the arterial wall. Moreover, low oscillatory WSS has been shown to disturb endothelial cells in a number of locations of the arterial tree (cerebral aneurysms, coronaries) which may induce a larger permeability of the wall. It is well known that larger TAWSS is often associated with lower oscillatoryWSS and lower residence time of particles. Therefore, our findings lead to the hypothesis that relatively higher TAWSS may induce a 'washing effect', limiting this advection of macromolecules. The phenomenon of 'outward convection' was recently defined by (Michel et al. 2018). They showed that it is dependent on hemodynamic factors, such as pressure and wall shear stress, and on the aortic properties, such as permeability. More specifically, this biomechanical phenomenon results into blood-borne plasminogen infiltrating in the arterial wall. This may induce a proteolytic injury and cause damage of the extracellularmatrix, in particular elastin. This would explain why the higher ultimate stress were found for aTAA exposed to higher WSS and weaker properties (lower rupture stretch) were obtained for aTAA having smaller values of TAWSS. According with these trends, the WSSmax and the TAWSSmax negatively correlate with gammastretch and Ephysio. This stretch criteria ranges between 0 and 1. The closer it is to 1, the larger is the risk of rupture. From our results, high value of gammastretch are associated to lower WSSmax and TAWSSmax. However, these results still need to be confirmed on a larger cohort and also to be reconciled with the results of (Guzzardi et al. 2015) who showed more elastin damage in the ascending aorta of BAV patients in the regions exposed to largerWSS. However, these studies cannot be directly compared considering that (Guzzardi et al. 2015) looked at regional correlations betweenWSS and elastin proteolysis whereas our study found inter-individual correlations betweenWSS and rupture properties. 4. Conclusion In conclusion, this study demonstrates that large TAWSS have a protective effect in ATAA as they are related to larger rupture properties and smaller stiffness. Further investigations will be extended to a bigger cohort of patients. (Figure Presented).