Changes in transmural mass transport correlate with ascending thoracic aortic aneurysm diameter in a fibulin-4 E57K knockin mouse model.

Thoracic aortic aneurysm is characterized by dilation of the aortic diameter by greater than 50%, which can lead to dissection or rupture. Common histopathology includes extracellular matrix remodeling that may affect transmural mass transport, defined as the movement of fluids and solutes across the wall. We measured in vitro ascending thoracic aorta mass transport in a mouse model with partial aneurysm phenotype penetration due to a mutation in the extracellular matrix protein fibulin-4 [Fbln4E57K/E57K, referred to as MU-A (aneurysm) or MU-NA (no aneurysm)]. To push the aneurysm phenotype, we also included MU mice with reduced levels of lysyl oxidase [Fbln4E57K/E57K;Lox+/-, referred to as MU-XA (extreme aneurysm)] and compared all groups to wild-type (WT) littermates. The phenotype variation allows investigation of how aneurysm severity correlates with mass transport parameters and extracellular matrix organization. We found that MU-NA ascending thoracic aortae have similar hydraulic conductance (Lp) to WT, but 397% higher solute permeability (ω) for 4 kDa FITC-dextran. In contrast, MU-A and MU-XA ascending thoracic aortae have 44-68% lower Lp and similar ω to WT. The results suggest that ascending thoracic aortic aneurysm progression involves an initial increase in ω, followed by a decrease in Lp after the aneurysm has formed. All MU ascending thoracic aortae are longer and have increased elastic fiber fragmentation in the extracellular matrix. There is a negative correlation between diameter and Lp or ω in MU ascending thoracic aortae. Changes in mass transport due to elastic fiber fragmentation could contribute to aneurysm progression or be leveraged for treatment.NEW & NOTEWORTHY Transmural mass transport is quantified in the ascending thoracic aorta of mice with a mutation in fibulin-4 that is associated with thoracic aortic aneurysms. Fluid and solute transport depend on aneurysm severity, correlate with elastic fiber fragmentation, and may be affected by proteoglycan deposition. Transport properties of the ascending thoracic aorta are provided and can be used in computational models. The changes in mass transport may contribute to aneurysm progression or be leveraged for aneurysm treatment.

Three-dimensional parametric modeling of bicuspid aortopathy and comparison with computational flow predictions.

Bicuspid aortic valve (BAV)-associated ascending aneurysmal aortopathy (namely "bicuspid aortopathy") is a heterogeneous disease making surgeon predictions particularly challenging. Computational flow analysis can be used to evaluate the BAV-related hemodynamic disturbances, which likely lead to aneurysm enlargement and progression. However, the anatomic reconstruction process is time consuming so that predicting hemodynamic and structural evolution by computational modeling is unfeasible in routine clinical practice. The aim of the study was to design and develop a parametric program for three-dimensional (3D) representations of aneurysmal aorta and different BAV phenotypes starting from several measures derived by computed-tomography angiography (CTA). Assuming that wall shear stress (WSS) has an important implication on bicuspid aortopathy, computational flow analyses were then performed to estimate how different would such an important parameter be, if a parametric aortic geometry was used as compared to standard geometric reconstructions obtained by CTA scans. Morphologic parameters here documented can be used to rapidly model the aorta and any phenotypes of BAV. t-test and Bland-Altman plot demonstrated that WSS obtained by flow analysis of parametric aortic geometries was in good agreement with that obtained from the flow analysis of CTA-related geometries. The proposed program offers a rapid and automated tool for 3D anatomic representations of bicuspid aortopathy with promising application in routine clinical practice by reducing the amount of time for anatomic reconstructions.

Temporal evolution of ascending aortic aneurysm wall stress predicts all-cause mortality.

OBJECTIVES: Diameter-based risk stratification for elective repair of ascending aortic aneurysm fails to prevent type A dissection in many patients. Aneurysm wall stresses may contribute to risk prediction; however, rates of wall stress change over time are poorly understood. Our objective was to examine aneurysm wall stress changes over 3-5 years and subsequent all-cause mortality. METHODS: Male veterans with <5.5 cm ascending aortic aneurysms and computed tomography at baseline and 3- to 5-year follow-up underwent three-dimensional aneurysm model construction. Peak circumferential and longitudinal wall stresses at systole were calculated using finite element analysis. Temporal trends were assessed by mixed-effects modelling. Changes in aortic wall stresses, diameter and length over time were evaluated as predictors of subsequent 3-year all-cause mortality by Cox proportional hazards modelling. RESULTS: Sixty-two male veterans were included in the study. Yearly changes in geometric and biomechanical measures were 0.12 mm/year (95% confidence interval, 0.04-0.20) for aortic diameter, 0.41 mm/year (0.12-0.71) for aortic length, 1.19 kPa/year -5.94 to 8.33) for peak circumferential stress, and 0.48 kPa/year (-3.89 to 4.84) for peak longitudinal stress. Yearly change in peak circumferential stress was significantly associated with hazard of death-hazard ratio for peak circumferential stress growth per 10 kPa/year, 1.27 (95% CI, 1.02-1.60; P = 0.037); hazard ratio for peak circumferential stress growth ≥ 32 kPa/year, 8.47 (95% CI, 2.42-30; P < 0.001). CONCLUSIONS: In this population of nonsurgical aneurysm patients, large temporal changes in peak circumferential stress, but not aortic diameter or length, was associated with all-cause mortality. Biomechanical stress and stress changes over time may be beneficial as additional risk factors for elective surgery in small aneurysms.

Insights into ascending aortic aneurysm: Interactions between biomechanical properties of the aortic wall and tissue biomarkers.

Background: It remains difficult to understand the association between the local mechanical properties of ascending thoracic aorta aneurysm (asTAA), its tissue, and its cellular and molecular changes. The purpose of our study was to investigate the relationship between biomechanical properties, histopathological findings, and tissue biomarkers of asTAA. Methods: Intraoperative asTAA samples from 30 patients were studied. All samples were examined histologically and underwent a tensile test. We determined the tensile strength (σв, MPa), the strain (ε, mm/mm˟%), and the area under the strength-strain curve (S) along with the concentrations of tissue matrix metalloproteinases (MMP-1 et al.) and their inhibitors, their interleukins (IL) -6 -10, and their tumor necrosis factor (TNF) -α. Results: It was found that 43.3 % of asTAA patients had atherosclerosis, 3.3 % had aortitis, and 53.3 % of patients had connective tissue dysplasia. Differences in the studied parameters between these subgroups were not found. Age correlated with ε (r = -0.49) and S (r = -0.54). ε was also associated with media fibrosis degree (r = -0.5), collagen/elastin ratio (r = -0.61), and IL-10 (r = 0.52). IL-10 correlated with collagen/elastin ratio (r = -0.58), TNF-α (r = 0.77), and MMP-1 (r = 0.71). Conclusion: Tissue IL-10 has a protective effect on the elastic structures of the aortic wall and is positively associated with the activity of MMP-1 and pro-inflammatory cytokines. IL-6 is associated with media fibrosis degree, and negatively affects strength-strain parameters of asTAA samples.

Region-specific delamination strength of ascending thoracic aortic aneurysm of elderly hypertensive patients with bicuspid and tricuspid aortic valves.

Both ageing and hypertension are clinical factors that may lead to a higher propensity for dissection or rupture of ascending thoracic aortic aneurysms (ATAAs). This study sought to investigate effect of valve morphology on regional delamination strength of ATAAs in the elderly hypertensive patients. Whole fresh ATAA samples were harvested from 23 hypertensive patients (age, 71 ± 8 years) who underwent elective aortic surgery. Peeling tests were performed to measure region-specific delamination strengths of the ATAAs, which were compared between patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). The regional delamination strengths of the ATAAs were further correlated with patient ages and aortic diameters for BAV and TAV groups. In the anterior and right lateral regions, the longitudinal delamination strengths of the ATAAs were statistically significantly higher for BAV patients than TAV patients (33 ± 7 vs. 23 ± 8 mN/mm, p = 0.01; 30 ± 7 vs. 19 ± 9 mN/mm, p = 0.02). For both BAV and TAV patients, the left lateral region exhibited significantly higher delamination strengths in both directions than the right lateral region. Histology revealed that disruption of elastic fibers in the right lateral region of the ATAAs was more severe for the TAV patients than the BAV patients. A strong inverse correlation between longitudinal delamination strength and age was identified in the right lateral region of the ATAAs of the TAV patients. Results suggest that TAV-ATAAs are more vulnerable to aortic dissection than BAV-ATAAs for the elderly hypertensive patients. Regardless of valve morphotypes, the right lateral region may be a special quadrant which is more likely to initiate dissection when compared with other regions.

From Biomechanical Properties to Morphological Variations: Exploring the Interplay between Aortic Valve Cuspidity and Ascending Aortic Aneurysm.

Background: This research explores the biomechanical and structural characteristics of ascending thoracic aortic aneurysms (ATAAs), focusing on the differences between bicuspid aortic valve aneurysms (BAV-As) and tricuspid aortic valve aneurysms (TAV-As) with non-dilated aortas to identify specific traits of ATAAs. Methods: Clinical characteristics, laboratory indices, and imaging data from 26 adult patients operated on for aneurysms (BAV-A: n = 12; TAV-A: n = 14) and 13 controls were analyzed. Biomechanical parameters (maximal aortic diameter, strain, and stress) and structural analyses (collagen fiber organization, density, fragmentation, adipocyte deposits, and immune cell infiltration) were assessed. Results: Significant differences in biomechanical parameters were observed. Median maximal strain was 40.0% (control), 63.4% (BAV-A), and 45.3% (TAV-A); median maximal stress was 0.59 MPa (control), 0.78 MPa (BAV-A), and 0.48 MPa (TAV-A). BAV-A showed higher tangential modulus and smaller diameter, with substantial collagen fragmentation (p < 0.001 vs. TAV and controls). TAV-A exhibited increased collagen density (p = 0.025), thickening between media and adventitia layers, and disorganized fibers (p = 0.036). BAV-A patients had elevated adipocyte deposits and immune cell infiltration. Conclusions: This study highlights distinct pathological profiles associated with different valve anatomies. BAV-A is characterized by smaller diameters, higher biomechanical stress, and significant collagen deterioration, underscoring the necessity for tailored clinical strategies for effective management of thoracic aortic aneurysm.

Effect of hypertension on the delamination and tensile strength of ascending thoracic aortic aneurysm with a focus on right lateral region.

Hypertension is a major predisposing factor to initiate thoracic aortopathy. The objective of this study is to investigate effect of hypertension on delamination and tensile strength of ascending thoracic aortic aneurysms (ATAAs). A total of 35 fresh ATAA samples were harvested from 19 hypertensive and 16 non-hypertensive patients during elective aortic surgery. Peeling tests with two extension rates were performed to determine delamination strength, while uniaxial tensile (UT) tests were employed to measure failure stresses. The delamination strength and failure stresses of the ATAAs were further correlated with patient ages for hypertensive and non-hypertensive groups. The delamination strength to peel apart the ATAA tissue along the longitudinal direction was statistically significantly lower for the hypertensive patients than that of the non-hypertensive patients (35 ± 11 vs. 49 ± 9 mN/mm, p = 0.02). A higher delamination strength was measured if peeling was performed with a higher extension rate. The circumferential failure stresses were significantly lower for the hypertensive ATAAs than those of the non-hypertensive ATAAs (1.03 ± 0.27 vs. 1.43 ± 0.38 MPa, p = 0.02). Histology showed that laminar structures of elastic fibers were mainly disrupted in the hypertensive ATAAs. The longitudinal delamination strength of the ATAAs was significantly decreased and strongly correlated with ages for the hypertensive patients. Strong inverse correlations were also identified between the circumferential and longitudinal failure stresses of the ATAAs and ages for the hypertensive patients. Results suggest that the ATAAs of the elderly hypertensive patients may have a higher propensity for dissection or rupture. The dissection properties of the ATAA tissue are rate dependent.

Stiffness matters: Improved failure risk assessment of ascending thoracic aortic aneurysms.

Objectives: Rupture and dissection are feared complications of ascending thoracic aortic aneurysms caused by mechanical failure of the wall. The current method of using the aortic diameter to predict the risk of wall failure and to determine the need for surgical resection lacks accuracy. Therefore, this study aims to identify reliable and clinically measurable predictors for aneurysm rupture or dissection by performing a personalized failure risk analysis, including clinical, geometrical, histologic, and mechanical data. Methods: The study cohort consisted of 33 patients diagnosed with ascending aortic aneurysms without genetic syndromes. Uniaxial tensile tests until failure were performed to determine the wall strength. Material parameters were fitted against ex vivo planar biaxial data and in vivo pressure-diameter relationships at diastole and systole, which were derived from multiphasic computed tomography (CT) scans. Using the resulting material properties and in vivo data, the maximal in vivo stress at systole was calculated, assuming a thin-walled axisymmetric geometry. The retrospective failure risk was calculated by comparing the peak wall stress at suprasystolic pressure with the wall strength. Results: The distensibility coefficient, reflecting aortic compliance and derived from blood pressure measurements and multiphasic CT scans, outperformed predictors solely based on geometrical features in assessing the risk of aneurysm failure. Conclusions: In a clinical setting, multiphasic CT scans followed by the calculation of the distensibility coefficient are of added benefit in patient-specific, clinical decision-making. The distensibility derived from the aneurysm volume change has the best predictive power, as it also takes the axial stretch into account.

Ascending aortic volume: A feasible indicator for ascending aortic aneurysm elective surgery?

Diameter-based criterion have been widely adopted for preventive surgery of ascending thoracic aortic aneurysm (ATAA). However, recent and growing evidence has shown that diameter-based methods may not be sufficient for identifying patients who are at risk of an ATAA. In this study, fluid-structure interaction (FSI) analysis was performed on one-hundred ATAA geometries reconstructed from clinical data to examine the relationship between hemodynamic conditions, ascending aortic volume (AAV), ascending aortic curvature, and aortic ratios measured from the reconstructed 3D models. The simulated hemodynamic and biomechanical parameters were compared among different groups of ATAA geometries classified based on AAV. The ATAAs with enlarged AAV showed significantly compromised hemodynamic conditions and higher mechanical wall stress. The maximum oscillatory shear index (OSI), particle residence time (PRT) and wall stress (WS) were significantly higher in enlarged ATAAs compared with controls (0.498 [0.497, 0.499] vs 0.499 [0.498, 0.499], p = 0.002, 312.847 [207.445, 519.391] vs 996.047 [640.644, 1573.140], p < 0.001, 769.680 [668.745, 879.795] vs 1072.000 [873.060, 1280.000] kPa, p < 0.001, respectively). Values were reported as median with interquartile range (IQR). AAV was also found to be more strongly correlated with these parameters compared to maximum diameter. The correlation coefficient between AAV and average WS was as high as 0.92 (p < 0.004), suggesting that AAV might be a feasible risk identifier for ATAAs. STATEMENT OF SIGNIFICANCE: Ascending thoracic aortic aneurysm is associated with the risk of dissection or rupture, creating life-threatening conditions. Current surgical intervention guidelines are mostly diameter based. Recently, many studies proposed to incorporate other morphological parameters into the current clinical guidelines to better prevent severe adverse aortic events like rupture or dissection. The purpose of this study is to gain a better understanding of the relationship between morphological parameters and hemodynamic parameters in ascending aortic aneurysms using fluid-solid-interaction analysis on patient-specific geometries. Our results suggest that ascending aortic volume may be a better indicator for surgical intervention as it shows a stronger association with pathogenic hemodynamic conditions.

Regional biomechanical characterization of human ascending aortic aneurysms: Microstructure and biaxial mechanical response.

The ascending thoracic aortic aneurysm (ATAA) is a permanent dilatation of the vessel with a high risk of adverse events, and shows heterogeneous properties. To investigate regional differences in the biomechanical properties of ATAAs, tissue samples were collected from 10 patients with tricuspid aortic valve phenotype and specimens from minor, anterior, major, and posterior regions were subjected to multi-ratio planar biaxial extension tests and second-harmonic generation (SHG) imaging. Using the data, parameters of a microstructure-motivated constitutive model were obtained considering fiber dispersion. SHG imaging showed disruptions in the organization of the layers. Structural and material parameters did not differ significantly between regions. The non-symmetric fiber dispersion model proposed by Holzapfel et al. [25] was used to fit the data. The mean angle of collagen fibers was negatively correlated between minor and anterior regions, and the parameter associated with collagen fiber stiffness was positively correlated between minor and major regions. Furthermore, correlations were found between the stiffness of the ground matrix and the mean fiber angle, and between the parameter associated with the collagen fiber stiffness and the out-of-plane dispersion parameter in the posterior and minor regions, respectively. The experimental data collected in this study contribute to the biomechanical data available in the literature on human ATAAs. Region-specific parameters for the constitutive models are fundamental to improve the current risk stratification strategies, which are mainly based on aortic size. Such investigations can facilitate the development of more advanced finite element models capable of capturing the regional heterogeneity of pathological tissues. STATEMENT OF SIGNIFICANCE: Tissue samples of human ascending thoracic aortic aneurysms (ATAA) were collected. Samples from four regions underwent multi-ratio planar biaxial extension tests and second-harmonic generation imaging. Region-specific parameters of a microstructure-motivated model considering fiber dispersion were obtained. Structural and material parameters did not differ significantly between regions, however, the mean fiber angle was negatively correlated between minor and anterior regions, and the parameter associated with collagen fiber stiffness was positively correlated between minor and major regions. Furthermore, correlations were found between the stiffness of the ground matrix and the mean fiber angle, and between the parameter associated with the collagen fiber stiffness and the out-of-plane dispersion parameter in the posterior and minor regions, respectively. This study provides a unique set of mechanical and structural data, supporting the microstructural influence on the tissue response. It may facilitate the development of better finite element models capable of capturing the regional tissue heterogeneity.

Mechanics of ascending aortic aneurysms based on a modulus of elasticity dependent on aneurysm diameter and pressure.

The mechanical stresses and strains are examined, in ascending thoracic aortic aneurysm (aTAA) models, in a patient-specific aTAA as well as in healthy thoracic aortic models, via Finite Element Analysis. The aneurysms are assumed spherical, 1.5 mm thick, with diameters between 47 mm and 80 mm, eccentrically positioned. The geometry and wall thickness distribution of the aorta along its length are based on open literature data for an average patient age of 66.25 years, accounting for the Body Surface Area (BSA) parameter. The vessel wall material is assumed isotropic and incompressible, with its Young's modulus varying with the aneurysm diameter and the applied intraluminal pressure (120 mmHg to 240 mmHg). In the aTAAs, peak stresses were found to increase nonlinearly with aneurysm diameter (for a given pressure) tending to reach a plateau, appearing at the proximal area of the aneurysm, whereas lower stresses were found at its distal part and even smaller at the aneurysm maximum diameter. Regarding the patient-specific aTAA model, the peak stresses appeared at the distal part of the aneurysm where a tear of the intima layer was detected during surgical intervention. Peak strains exhibited for each pressure a maximum at a certain aneurysm diameter beyond which they dropped so that essentially the vessel wall's distensibility was thus reduced. Examining more than 100 geometry cases and employing a failure stress criterion, the rupture diameter thresholds were estimated to be 65, 52.5, 50 and 47.5 mm for a pressure of 120, 160, 200 and 240 mmHg respectively.

Geometry and flow in ascending aortic aneurysms are influenced by left ventricular outflow tract orientation: Detecting increased wall shear stress on the outer curve of proximal aortic aneurysms.

BACKGROUND: The geometrical characterization of ascending thoracic aortic aneurysms in clinical practice is limited to diameter measurements. Despite growing interest in hemodynamic assessment, its relationship with ascending thoracic aortic aneurysm pathogenesis is poorly understood. This study examines the relationship between geometry of the ventriculo-aortic junction and blood flow patterns in ascending thoracic aortic aneurysm disease. METHODS: Thirty-three patients with ascending thoracic aortic aneurysms (exclusions: bicuspid aortic valves, connective tissue disease) underwent 4-dimensional flow magnetic resonance imaging. After image segmentation, geometrical parameters were measured, including aortic curvature, tortuosity, length, and diameter. A unique angular measurement made by the trajectory of the left ventricular outflow tract axis and the proximal aorta was also conducted. Velocity profiles were quantitatively and qualitatively analyzed. In addition, 11 patients (33%) underwent wall shear stress mapping of the ascending thoracic aortic aneurysm region using computational fluid dynamics simulation. RESULTS: Greater left ventricular outflow tract aortic angles were associated with larger aortic diameters at the levels of the sinus (coefficient = 0.387, P = .014) and ascending aorta (coefficient = 0.284, P = .031). Patients with left ventricular outflow tract aortic angles greater than 60° had marked asymmetric flow acceleration on the outer curvature in the proximal aorta, ascertained from 4-dimensional flow analysis. For patients undergoing computational fluid dynamics assessment, regression analysis found that higher left ventricular outflow tract aortic angles were associated with significantly higher wall shear stress values in the outer curve of the aorta (coefficient 0.07, 95% confidence interval 0.04-0.11, P = .002): Angles greater than 50° yielded time-averaged wall shear stress values greater than 2.5 Pa, exhibiting a linear relationship. CONCLUSIONS: Our findings strengthen the hypothesis of flow-mediated ascending thoracic aortic aneurysm disease progression and that left ventricular outflow tract aortic angle may be a predictor of disease severity.

Gender differences in the dissection properties of ascending thoracic aortic aneurysms.

OBJECTIVES: Presentation, management and outcomes in the aortic dissection (AD) of ascending thoracic aortic aneurysm (ATAA) differ in gender and age. The purpose of this study is to investigate the dissection properties of male and female ATAAs. METHODS: Peeling tests were performed to quantitatively determine the delamination strength and dissection energy of 41 fresh ATAA samples (22 males and 19 females) in relatively young (≤65 years) and elderly (>65 years) patients. The delamination strength of the ATAAs was further correlated with patient ages for males and females. The histological investigation was employed to characterize the dissected morphology. RESULTS: For elderly patients, circumferential and longitudinal delamination strengths of the female ATAAs were statistically significantly lower than those of the males (circumferential: 31 ± 6 vs 42 ± 6 mN/mm, P < 0.01; longitudinal: 35 ± 7 vs 49 ± 10 mN/mm, P = 0.02). No significant differences were found in the delamination strength between males and females for relatively young patients. The circumferential and longitudinal delamination strengths were significantly decreased and strongly correlated with patient ages for females. However, these correlations were not present in males. Dissection routes propagated in the aortic media to create ruptured surfaces for all specimens. Peeling tests of the male ATAAs generate rougher surfaces than females. CONCLUSIONS: There is a higher propensity of AD occurrence for the elderly females as compared to males with matched ages. Surgeons should be cognizant of the risk of AD onset later in life, especially in females.

Existing and Emerging Approaches to Risk Assessment in Patients with Ascending Thoracic Aortic Dilatation.

Ascending thoracic aortic aneurysm is a life-threatening disease, which is difficult to detect prior to the occurrence of a catastrophe. Epidemiology patterns of ascending thoracic aortic dilations/aneurysms remain understudied, whereas the risk assessment of it may be improved. The electronic databases PubMed/Medline 1966-2022, Web of Science 1975-2022, Scopus 1975-2022, and RSCI 1994-2022 were searched. The current guidelines recommend a purely aortic diameter-based assessment of the thoracic aortic aneurysm risk, but over 80% of the ascending aorta dissections occur at a size that is lower than the recommended threshold of 55 mm. Moreover, a 55 mm diameter criterion could exclude a vast majority (up to 99%) of the patients from preventive surgery. The authors review several visualization-based and alternative approaches which are proposed to better predict the risk of dissection in patients with borderline dilated thoracic aorta. The imaging-based assessments of the biomechanical aortic properties, the Young's elastic modulus, the Windkessel function, compliance, distensibility, wall shear stress, pulse wave velocity, and some other parameters have been proposed to improve the risk assessment in patients with ascending thoracic aortic aneurysm. While the authors do not argue for shifting the diameter threshold to the left, they emphasize the need for more personalized solutions that integrate the imaging data with the patient's genotypes and phenotypes in this heterogeneous pathology.

Mechanical characterization and material modeling of ascending aortic aneurysm with different bicuspid aortic cusp fusion morphologies.

Bicuspid aortic valve (BAV) is frequently associated with ascending thoracic aortic aneurysm (ATAA). Impact of cusp fusion patterns on biomechanics and microstructure of the ATAA remains unknown. This study aims to investigate biaxial mechanical properties of the ATAAs with right-left (RL) and right-noncoronary (RN) cusp fusion patterns. Fresh ATAA samples (n = 26) were obtained from patients who underwent surgical aneurysm repair. Biaxial extension tests were performed to characterize mechanical behaviors of the RL and RN BAV-ATAAs. A material model was fitted to biaxial experimental data to obtain model parameters. Histological and mass fraction analyses were employed to investigate the underlying microstructure and dry weight percentages of elastin and collagen in the ATAA tissue. The RL and RN BAV-ATAAs exhibited nonlinear and anisotropic mechanical responses to biaxial loading. Tissue stiffness of the RN BAV-ATAAs was significantly higher than that of the RL BAV-ATAAs in the circumferential (2679 ± 755 vs 1942 ± 578 kPa, mean ± SD, p = 0.04) and longitudinal (2535 ± 630 vs 1709 ± 512 kPa, mean ± SD, p = 0.02) directions under the equibiaxial stresses. Laminar structure of elastic fibers was disrupted in both RL and RN BAV-ATAAs. Notably, interstitial fibrosis and thinner elastic fibers were identified in the RN BAV-ATAAs. Mass fraction of collagen was significantly higher for the RN BAV-ATAAs than that of the RL BAV-ATAAs. The tissue stiffness in the circumferential direction was significantly increased and strongly correlated with the mass fractions of collagen for both RL and RN BAV-ATAAs. Our results suggest that elastic properties of the RN BAV-ATAAs are more deteriorated than those of the RL BAV-ATAAs. Changes in biomechanical properties may have great impact on ascending aortic dilation.

Interaction of the Blood Components with Ascending Thoracic Aortic Aneurysm Wall: Biomechanical and Fluid Analyses.

BACKGROUND: Ascending thoracic aortic aneurysm (ATAA) is an asymptomatic localized dilation of the aorta that is prone to rupture with a high rate of mortality. While diameter is the main risk factor for rupture assessment, it has been shown that the peak wall stress from finite element (FE) simulations may contribute to refinement of clinical decisions. In FE simulations, the intraluminal boundary condition is a single-phase blood flow that interacts with the thoracic aorta (TA). However, the blood is consisted of red blood cells (RBCs), white blood cells (WBCs), and plasma that interacts with the TA wall, so it may affect the resultant stresses and strains in the TA, as well as hemodynamics of the blood. METHODS: In this study, discrete elements were distributed in the TA lumen to represent the blood components and mechanically coupled using fluid-structure interaction (FSI). Healthy and aneurysmal human TA tissues were subjected to axial and circumferential tensile loadings, and the hyperelastic mechanical properties were assigned to the TA and ATAA FE models. RESULTS: The ATAA showed larger tensile and shear stresses but smaller fluid velocity compared to the ATA. The blood components experienced smaller shear stress in interaction with the ATAA wall compared to TA. The computational fluid dynamics showed smaller blood velocity and wall shear stress compared to the FSI. CONCLUSIONS: This study is a first proof of concept, and future investigations will aim at validating the novel methodology to derive a more reliable ATAA rupture risk assessment considering the interaction of the blood components with the TA wall.

Biomechanics in ascending aortic aneurysms correlate with tissue composition and strength.

Objective: This study correlates low strain tangential modulus (LTM) and transition zone onset (TZo) stress, biomechanical parameters that occur within the physiological range of stress seen in vivo, with tissue strength and histopathologic changes in aneurysmal ascending aortic tissue. Method: Ascending aortic aneurysm tissue samples were collected from 41 patients undergoing elective resection. Samples were subjected to planar biaxial testing to quantify LTM and TZo. These were then correlated with strength assessed from uniaxial testing and with histopathologic quantification of pathologic derangements in elastin, collagen, and proteoglycan (PG). Results: Decreased LTM and TZo were correlated with reduced strength (P < .05), PG content (P < .05), and elastin content (P < .05). Reduced TZo also was correlated with increased elastin fragmentation (P < .05). Conclusions: LTM and TZo are correlated with common biomechanical and histopathologic alterations in ascending aortic aneurysm tissue that are thought to relate to the risk of acute aortic syndromes. LTM and TZo are measured under conditions approximating in vivo physiology and have the potential to be obtained noninvasively using medical imaging techniques. Therefore, they represent parameters that warrant future study as potential contributors to our growing knowledge of pathophysiology, disease progression, and risk stratification of aortic disease.

New indicators for systematic assessment of aortic morphology: a narrative review.

In order to prevent the occurrence of aortic adverse events in ascending thoracic aortic aneurysm patients, preventive surgery is the sole option in case of large aneurysm. Identifying high-risk patients timely and accurately requires effective predictive indicators of aortic adverse events and accurate risk stratification thresholds. Absolute diameter measured after a single imaging examination, which has been used as the predictive indicator for decades, has been proved to be ineffective for risk stratification in moderately dilated aorta. Previously, new indicators combining absolute diameters with personalized parameters have been reported to show better predictive power of aortic adverse events than absolute diameters by correcting the effect of these parameters on the diameters. Meanwhile, combining three-dimensional parameters to formulate risk stratification thresholds not only may characterize the aortic risk morphology more precisely, but also predict aortic adverse events more accurately. These new indicators may provide more systematic assessment methods of patients' risk, formulate more personalized intervention strategies for ascending thoracic aortic aneurysm patients, and also provide a basis for researchers to develop more accurate and effective risk thresholds. We also highlight that the algorithm obtained by combining multiple indicators may be a better choice compared with single indicator, but this still requires the support of more evidence. Due to the particularity of syndromic aortic disease, whether these new indicators can be used for its risk stratification is still uncertain. Therefore, the scope of this manuscript does not include this kind of disease.

Coupling hemodynamics with mechanobiology in patient-specific computational models of ascending thoracic aortic aneurysms.

BACKGROUND AND OBJECTIVE: The prevention of ascending thoracic aortic aneurysms (ATAAs), which affect thousands of persons every year worldwide, remains a major issue. ATAAs may be caused by anything that weakens the aortic wall. Altered hemodynamics, which concerns a majority of patients with bicuspid aortic valves, has been shown to be related to such weakening and to contribute to ATAA development and progression. However the underlying mechanisms remain unclear and computational modeling in this field could help significantly to elucidate how hemodynamics and mechanobiology interact in ATAAs. METHODS: Accordingly, we propose a numerical framework combining computational fluid dynamics and 4D flow magnetic resonance imaging (MRI) coupled with finite element (FE) analyses to simulate growth and remodeling (G&R) occurring in patient-specific aortas in relation with altered hemodynamics. The geometries and the blood velocities obtained from 4D flow MRI are used as boundary conditions for CFD simulations. CFD simulations provide an estimation of the wall shear stress (WSS) and relative residence time (RRT) distribution across the luminal surface of the wall. An initial insult is then applied to the FE model of the aortic wall, assuming that the magnitude of the insult correlates spatially with the normalized RRT distribution obtained from CFD simulations. G&R simulations are then performed. The material behavior of each Gauss point in these FE models is evolved continuously to compensate for the deviation of the actual wall stress distribution from the homeostatic state after the initial insult. The whole approach is illustrated on two healthy and two diseased subjects. The G&R parameters are calibrated against previously established statistical models of ATAA growth rates. RESULTS: Among the variety of results provided by G&R simulations, the analysis focused especially on the evolution of the wall stiffness, which was shown to be a major risk factor for ATAAs. It was shown that the G&R parameters, such as for instance the rate of collagen production or cell mechanosensitivity, play a critical role in ATAA progression and remodeling. CONCLUSIONS: These preliminary findings show that patient-specific computational modeling coupling hemodynamics with mechanobiology is a promising approach to explore aneurysm progression.

Failure properties of ascending thoracic aortic aneurysms with dysfunctional tricuspid aortic valves.

OBJECTIVES: Ascending thoracic aortic aneurysms (ATAAs) often coexist with dysfunctional tricuspid aortic valves (TAVs). How valvular pathology relates to the aortic wall mechanical properties requires detailed examination. METHODS: Intact-wall and layer-specific mechanical properties from 40 and 21 patients with TAV-ATAAs, respectively, were studied using uniaxial tensile testing, longitudinally and circumferentially. Failure stress (tensile strength), failure stretch (extensibility) and peak elastic modulus (stiffness) measurements, along with histological assays of thickness and elastin/collagen contents, were compared among patients with no valvular pathology (NVP), aortic stenosis (AS) or aortic insufficiency (AI). RESULTS: Intact-wall stiffness longitudinally and medial strength and stiffness, in either direction, were significantly lower in AI patients than in AS and NVP patients. Intact-wall/medial thickness and extensibility in either direction were significantly lower in AS patients than in AI and NVP patients. In contrast, intact-wall/medial stiffness circumferentially was significantly higher in AS patients than in NVP patients, consistent with the significantly increased medial collagen in AS patients. Failure properties and medial thickness and elastin/collagen contents were significantly lower (more impaired) in females. The left lateral was the thickest quadrant in NVP patients, but the 4 quadrants were equally thick in AS and AI patients. There were significant differences in strength and stiffness among quadrants, which varied however in the 3 patient groups. CONCLUSIONS: The aortic wall load-bearing capacity was impaired in patients with ATAA in the presence of TAV stenosis or insufficiency. These findings lend biomechanical support to the current guidelines suggesting lower thresholds for elective ascending aorta replacement in cases of aortic valve surgery.