Identification of circumferential regional heterogeneity of ascending thoracic aneurysmal aorta by biaxial mechanical testing.

Ascending thoracic aortic aneurysm (ATAA) in patients with bicuspid aortic valve (BAV) can present an asymmetrical aortic dilatation compared with patients with tricuspid aortic valve (TAV). This pattern of aneurysm dilatation led us to hypothesize that biomechanical differences likely induced by regional heterogeneity of material properties can underlie the observed asymmetric enlargement discrepancies between BAV ATAA and TAV ATAA. This study aimed to characterize the mechanical properties and associated aortic tissue stiffness changes along the circumferential direction of aortic rings collected from surgically-repaired patients with ATAA. Biaxial material testing was performed on tissue specimens extrapolated from all aortic quadrants (i.e. anterior, posterior, major and minor curvature of the aorta), and then the tissue stiffness was quantified at both physiological and supra-physiological stress levels (i.e. 142 kPa and 242 kPa, respectively). Tissue stiffness revealed that the major curvature of BAV ATAA is statistically less stiff than the anterior quadrant (276.6 ±â€¯137.1 kPa for BAV ATAA and 830.1 ±â€¯557.1 kPa for BAV ATAA, p = .024, at 142 kPa) and to that of major curvature of TAV ATAA (276.6 ±â€¯137.0 kPa for BAV ATAA and 733.2 ±â€¯391.1 kPa for TAV ATAA, p = .001, at 142 kPa), suggesting local weakening of bicuspid aortic wall. Multiphoton imaging revealed local changes on elastic fiber networks. The recovered material parameters for the Fung-type constitutive model are crucial for reliable stress predictions while the information on regional tissue stiffness changes are fundamental to develop risk stratification strategies not based on aortic size.

Engineering in-plane mechanics of electrospun polyurethane scaffolds for cardiovascular tissue applications.

Effective cardiovascular tissue surrogates require high control of scaffold structural and mechanical features to match native tissue properties, which are dependent on tissue-specific mechanics, function heterogenicity, and morphology. Bridging scaffold processing variables with native tissue properties is recognized as a priority for advancing biomechanical performance of biomedical materials and, when translated to the clinical practice, their efficacy. Accordingly, this study selected electrospinning on a rotating cylindrical target as an apparatus of broad application and mapped the relationship between key processing variables and scaffold mechanics and structure. This information was combined with mechanical anisotropy ranges of interest for the three main categories of tissue surrogated in cardiovascular tissue engineering: heart valve leaflets, ventricle wall, and large diameter blood vessels. Specifically, three processing variables have been considered: the rotational velocity and the rastering velocity of the mandrel and the dry (single nozzle - polymer only) vs wet (double nozzle - polymer plus phosphate buffer saline solution) fabrication configuration. While the dry configuration is generally utilized to obtain micro-fiber based polymeric mats, the wet fabrication is representative of processing conditions utilized to incorporate cells, growth factors, or micro-particles within the fibrous scaffold matrix. Dry and wet processed electrospun mats were fabricated with tangential and rastering velocities within the 0.3-9.0 m/s and 0.16-8 cm/s range respectively. Biaxial mechanics, fiber network, and pore micro-architectures were measured for each combination of velocities and for each fabrication modality (dry and wet). Results allowed identification of the precise combination of rotational and rastering velocities, for both dry and wet conditions, that is able to recapitulate the native cardiovascular tissue anisotropy ratio. By adopting a simple and broadly utilized electrospinning layout, this study is meant to provide a repeatable and easy to access methodology to improve biomimicry of the in plane-mechanics of heart valve leaflets, ventricular wall, and large diameter blood vessels.

Patient-specific computational evaluation of stiffness distribution in ascending thoracic aortic aneurysm.

Quantifying local aortic stiffness properties in vivo is acknowledged as essential to assess the severity of an ascending thoracic aortic aneurysm (ATAA). Recently, the LESI (local extensional stiffness identification) methodology has been established to quantify non-invasively local stiffness properties of ATAAs using electrocardiographic-gated computed tomography (ECG-gated CT) scans. The aim of the current study was to determine the most sensitive markers of local ATAA stiffness estimation with the hypothesis that direct measures of local ATAA stiffness could better detect the high-risk patients. A cohort of 30 patients (12 BAV and 18 TAV) referred for aortic size evaluation by ECG-gated CT were recruited. For each patient, the extensional stiffness Q was evaluated by the LESI methodology whilst computational flow analyses were also performed to derive hemodynamics markers such as the wall shear stress (WSS). A strong positive correlation was found between the extensional stiffness and the aortic pulse pressure (R = 0.644 and p < 0.001). Interestingly, a significant positive correlation was also found between the extensional stiffness and patients age for BAV ATAAs (R = 0.619 and p = 0.032), but not for TAV ATAAs (R = -0.117 and p = 0.645). No significant correlation was found between the extensional stiffness and WSS evaluated locally. There was no significant difference either in the extensional stiffness between BAV ATAAs and TAV ATAAs (Q = 3.6 ± 2.5 MPa.mm for BAV ATAAs vs Q = 5.3 ± 3.1 MPa.mm for TAV ATAAs, p = 0.094). Future work will focus on relating the extensional stiffness to the patient-specific rupture risk of ATAAs on larger cohorts to confirm the promising interest of the LESI methodology.

Simulation study of transcatheter heart valve implantation in patients with stenotic bicuspid aortic valve.

Bicuspid aortic valve (BAV) anatomy has routinely been considered an exclusion in the setting of transcatheter aortic valve implantation (TAVI) because of the large dimension of the aortic annulus having a more calcified, bulky, and irregular shape. The study aims to develop a patient-specific computational framework to virtually simulate TAVI in stenotic BAV patients using the Edwards SAPIEN 3 valve (S3) and its improved version SAPIEN 3 Ultra and quantify stent frame deformity as well as the severity of paravalvular leakage (PVL). Specifically, the aortic root anatomy of n.9 BAV patients who underwent TAVI was reconstructed from pre-operative CT imaging. Crimping and deployment of S3 frame were performed and then followed by fluid-solid interaction analysis to simulate valve leaflet dynamics throughout the entire cardiac cycle. Modeling revealed that the S3 stent frame expanded well on BAV anatomy with an elliptical shape at the aortic annulus. Comparison of predicted S3 deformity as assessed by eccentricity and expansion indices demonstrated a good agreement with the measurement obtained from CT imaging. Blood particle flow analysis demonstrated a backward blood jet during diastole, whereas the predicted PVL flows corresponded well with those determined by transesophageal echocardiography. This study represents a further step towards the use of personalized simulations to virtually plan TAVI, aiming at improving not only the efficacy of the implantation but also the exploration of "off-label" applications as the TAVI in the setting of BAV patients. Graphical abstract Computational frameworks of TAVI in patients with stenotic bicuspid aortic valve.

Shear Stress and Aortic Strain Associations With Biomarkers of Ascending Thoracic Aortic Aneurysm.

BACKGROUND: This study aims to investigate the association of wall shear stress (WSS) and aortic strain with circulating biomarkers including matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinase (TIMP), and exosomal level of microRNA (miRNA) in ascending aortic aneurysms of patients with bicuspid or tricuspid aortic valve. METHODS: A total of 76 variables from 125 patients with ascending aortic aneurysms were collected from (1) blood plasma to measure plasma levels of miRNAs and protein activity; (2) computational flow analysis to estimate peak systolic WSS and time-average WSS (TAWSS); and (3) imaging analysis of computed tomography angiography to determine aortic wall strain. Principal component analysis followed by logistic regression allowed the development of a predictive model of aortic surgery by combining biomechanical descriptors and biomarkers. RESULTS: The protein activity of MMP-1, TIMP-1, and MMP-2 was positively correlated to the systolic WSS and TAWSS observed in the proximal ascending aorta (eg, R = 0.52, P < .001, for MMP-1 with TAWSS) where local maxima of WSS were found. For bicuspid patients, aortic wall strain was associated with miR-26a (R = 0.55, P = .041) and miR-320a (R = 0.69, P < .001), which shows a significant difference between bicuspid and tricuspid patients. Receiver-operating characteristics curves revealed that the combination of WSS, MMP-1, TIMP-1, and MMP-12 is predictive of aortic surgery (area under the curve 0.898). CONCLUSIONS: Increased flow-based and structural descriptors of ascending aortic aneurysms are associated with high levels of circulating biomarkers, implicating adverse vascular remodeling in the dilated aorta by mechanotransduction. A combination of shear stress and circulating biomarkers has the potential to improve the decision-making process for ascending aortic aneurysms to a highly individualized level.

Comparison of hemodynamic and structural indices of ascending thoracic aortic aneurysm as predicted by 2-way FSI, CFD rigid wall simulation and patient-specific displacement-based FEA.

Patient-specific computational modeling is increasingly being used to predict structural and hemodynamic parameters, especially when current clinical tools are not accessible. Indeed, pathophysiology of ascending thoracic aortic aneurysm (ATAA) has been simulated to quantify the risk of complications by novel prognostic parameters and thus to improve the clinical decision-making process related to the intervention of ATAAs. In this study, the relevance of aneurysmal wall elasticity in determining parameters of clinical importance, such as the wall shear stress (WSS), is discussed together with the significance of applying realistic boundary conditions to consider the aortic stretch and twist transmitted by the heart motion. Results from both finite element analysis (FEA) and computational fluid-dynamic (CFD) were compared to those of 2-way fluid-solid interaction analyses (FSI), which were carried out on ATAAs with either bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV). Although both the shear and intramural stress spatial distributions were found different for a given ATAA, correlation analysis and Bland-Altman plots demonstrated that CFD-related WSS and FEA-related IMS predictions were comparable with those derived by the more sophisticated 2-way FSI modeling. This is likely caused by the stiff aneurysmal wall showing reduced diameter changes over the cardiac beating (ie, 4.2 ±â€¯2.4%). Therefore, with the fact that there is no gold-standard for the assessment of hemodynamic and structural mechanics of ATAAs and with accepted limitations of our approach, computational technique has to be verified before applications in routine clinical practice as demonstrated in this study.

In Vivo Strain Analysis of Dilated Ascending Thoracic Aorta by ECG-Gated CT Angiographic Imaging.

Accurate assessment of aortic extensibility is a requisite first step for elucidating the pathophysiology of an ascending thoracic aortic aneurysm (ATAA). This study aimed to develop a framework for the in vivo evaluation of the full-field distribution of the aortic wall strain by imaging analysis of electrocardiographic- (ECG) gated thoracic data of 34 patients with ATAA. Seven healthy controls (i.e., non-aneurysmal aorta) from patients who underwent ECG-gated CT angiography for coronary artery diseases were included for comparison. To evaluate the systolic function, ECG-gated computed tomography (CT) angiography was used to generate patient-specific geometric meshes of the ascending aorta, and then to estimate both the displacement and strain fields using a mathematical algorithm. Results evidenced stiff behavior for the aneurysmal aorta compared with that of the healthy ascending aorta of the controls, with patients over 55 years of age displaying significantly lower extensibility. Moreover, the patient risk as quantified by the ratio of in vivo strain to the ruptured one increased significantly with increased systolic blood pressure, older age, and higher pressure-strain modulus. Statistical analysis also indicated that an increased pressure-strain modulus is a risk factor for ATAAs with bicuspid aortic valve, suggesting a different mechanism of failure in these patients. The approach here proposed for the in vivo evaluation of the aortic wall strain is simple and fast, with promising applicability in routine clinical imaging, and could be used to develop a rupture potential criterion on the basis of the aortic aneurysm extensibility.