Specimen width affects vascular tissue integrity for in-vitro characterisation.

The preparation of slender specimens for in-vitro tissue characterisation could potentially alter mechanical tissue properties. To investigate this factor, rectangular specimens were prepared from the wall of the porcine aorta for uniaxial tensile loading. Varying strip widths of 16 mm, 8 mm, and 4 mm were achieved by excising zero, one, and three cuts within the specimen along the loading direction, respectively. While specimens loaded along the vessel's circumferential direction acquired consistent tissue properties, the width of test specimens influenced the results of axially loaded tissue; vascular wall stiffness was reduced by approximately 40% in specimens with strips 4 mm wide. In addition, the cross-loading stretch was strongly influenced by specimen strip width, and fiber sliding contributed to the softening of slender tensile specimens, an outcome from finite element analysis of test specimens. We may, therefore, conclude that cutting orthogonal to the main direction of collagen fibers introduces mechanical trauma that weakens slender tensile specimens, compromising the determination of representative mechanical vessel wall properties.

On the Impact of Residual Strains in the Stress Analysis of Patient-Specific Atherosclerotic Carotid Vessels: Predictions Based on the Homogenous Stress Hypothesis.

The identification of carotid atherosclerotic lesion at risk for plaque rupture, eventually resulting in cerebral embolism and stroke, is of paramount clinical importance. High stress in the fibrous plaque cap has been proposed as risk factor. However, among others, residual strains influence said stress predictions, but quantitative and qualitative implications of residual strains in this context are not well explored. We therefore propose a multiplicative kinematics-based Growth and Remodeling (G&R) framework to predict residual strains from homogenizing tissue stress and then investigate its implication on plaque stress. Carotid vessel morphology of four patients was reconstructed from clinical Computed Tomography-Angiography (CT-A) images and equipped with heterogeneous tissue constitutive properties assigned through a histology-based artificial intelligence image segmentation tool. As compared to a purely elastic analysis and depending on patient-specific morphology and tissue distributions, the incorporation of residual strains reduced the maximum wall stress by up to 30 % and resulted in a fundamentally different distribution of stress across the atherosclerotic wall. Regardless residual strains homogenized tissue stresses, the fibrous plaque cap may persistently be exposed to spots of high stress. In conclusion, the incorporation of residual strains in biomechanical studies of atherosclerotic carotids may be important for a reliable assessment of fibrous plaque cap stress.

Fracture of porcine aorta. Part 2: FEM modelling and inverse parameter identification.

The mechanics of vascular tissue, particularly its fracture properties, are crucial in the onset and progression of vascular diseases. Vascular tissue properties are complex, and the identification of fracture mechanical properties relies on robust and efficient numerical tools. In this study, we propose a parameter identification pipeline to extract tissue properties from force-displacement and digital image correlation (DIC) data. The data has been acquired by symconCT testing porcine aorta wall specimens. Vascular tissue is modelled as a non-linear viscoelastic isotropic solid, and an isotropic cohesive zone model describes tissue fracture. The model closely replicated the experimental observations and identified the fracture energies of 1.57±0.82 kJ m-2 and 0.96±0.34 kJ m-2 for rupturing the porcine aortic media along the circumferential and axial directions, respectively. The identified strength was always below 350 kPa, a value significantly lower than identified through classical protocols, such as simple tension, and sheds new light on the resilience of the aorta. Further refinements to the model, such as considering rate effects in the fracture process zone and tissue anisotropy, could have improved the simulation results. STATEMENT OF SIGNIFICANCE: This paper identified porcine aorta's biomechanical properties using data acquired through a previously developed experimental protocol, the symmetry-constraint compact tension test. An implicit finite element method model mimicked the test, and a two-step approach identified the material's elastic and fracture properties directly from force-displacement curves and digital image correlation-based strain measurements. Our findings show a lower strength of the abdominal aorta as compared to the literature, which may have significant implications for the clinical evaluation of the risk of aortic rupture.

Three-dimensional growth and biomechanical risk progression of abdominal aortic aneurysms under serial computed tomography assessment.

Growth of abdominal aortic aneurysms (AAAs) is often described as erratic and discontinuous. This study aimed at describing growth patterns of AAAs with respect to maximal aneurysm diameter (Dmax) and aneurysm volume, and to characterize changes in the intraluminal thrombus (ILT) and biomechanical indices as AAAs grow. 384 computed tomography angiographies (CTAs) from 100 patients (mean age 70.0, standard deviation, SD = 8.5 years, 22 women), who had undergone at least three CTAs, were included. The mean follow-up was 5.2 (SD = 2.5) years. Growth of Dmax was 2.64 mm/year (SD = 1.18), volume 13.73 cm3/year (SD = 10.24) and PWS 7.3 kPa/year (SD = 4.95). For Dmax and volume, individual patients exhibited linear growth in 87% and 77% of cases. In the tertile of patients with the slowest Dmax-growth (< 2.1 mm/year), only 67% belonged to the slowest tertile for volume-growth, and 52% and 55% to the lowest tertile of PWS- and PWRI-increase, respectively. The ILT-ratio (ILT-volume/aneurysm volume) increased with time (2.6%/year, p < 0.001), but when adjusted for volume, the ILT-ratio was inversely associated with biomechanical stress. In contrast to the notion that AAAs grow in an erratic fashion most AAAs displayed continuous and linear growth. Considering only change in Dmax, however, fails to capture the biomechanical risk progression, and parameters such as volume and the ILT-ratio need to be considered.

Biomechanics and early sac regression after endovascular aneurysm repair of abdominal aortic aneurysm.

Background: Sac regression after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAA) is regarded as a marker of successful response to treatment. Several factors influence sac behavior after EVAR, yet little is known about the value of preoperative biomechanics. The aim of this study was to investigate the difference in aortic biomechanics between patients with and without sac regression. Methods: Patients treated with standard EVAR for infrarenal AAA at the Karolinska University Hospital between 2009 and 2012 with one preoperative and a minimum of two postoperative computed tomography angiography (CTA) scans were considered for inclusion in this single-center retrospective cohort study. Biomechanical indices such as AAA wall stress and wall stress-strength ratio as well as intraluminal thrombus (ILT) thickness and stress were measured preoperatively in A4ClinicRE (VASCOPS GmbH). AAA diameter and volume were analyzed on preoperative, 30-day, and 1-year CTAs. Patients were dichotomized based on sac regression, defined as a ≥ 5 mm decrease in maximal AAA diameter between the first two postoperative CTA scans. Multivariable logistic regression was used for analysis of factors associated with early sac regression. Results: Of the 101 patients treated during the inclusion period, 64 were included. Thirty-nine (61%) demonstrated sac regression and 25 (39%) had a stable sac or sac increase. The mean patients age (73 years vs 76 years), male sex (85% vs 96%), and median AAA diameter (58 mm vs 58.5 mm) did not differ between patients with and without sac regression. Although no difference in preoperative biomechanics was seen between the groups, multivariable logistic regression revealed that a larger AAA diameter (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.06-1.51; P = .009) and smoking (OR, 22.1; 95% CI, 2.78-174; P = .003) were positively associated with sac regression. In contrast, the lumen diameter (OR, 0.87; 95% CI, 0.77-0.98; P = .023), ILT thickness (OR, 0.85; 95% CI, 0.75-0.97; P = .013), aspirin or direct-acting oral anticoagulant use (OR, 0.11; 95% CI, 0.02-0.61; P = .012), and mean ILT stress (OR, 0.35; 95% CI, 0.14-0.87; P = .024) showed a negative association. Patients with sac regression had fewer reinterventions (log-rank P = .010) and lower mortality (log-rank P = .012) at the 5-year follow-up. Conclusions: This study, characterizing preoperative biomechanics in patients with and without sac regression, demonstrated a negative association between mean ILT stress and ILT thickness with a change in sac diameter after EVAR. Given that the ILT is a highly dynamic entity, further studies focusing on the role of the thrombus are needed. Furthermore, patients presenting with early sac regression had improved outcomes after EVAR.

Association between aortic peak wall stress and rupture index with abdominal aortic aneurysm-related events.

OBJECTIVE: The aim of this study was to assess whether aortic peak wall stress (PWS) and peak wall rupture index (PWRI) were associated with the risk of abdominal aortic aneurysm (AAA) rupture or repair (defined as AAA events) among participants with small AAAs. METHODS: PWS and PWRI were estimated from computed tomography angiography (CTA) scans of 210 participants with small AAAs (≥ 30 and ≤ 50 mm) prospectively recruited between 2002 and 2016 from two existing databases. Participants were followed for a median of 2.0 (inter-quartile range 1.9, 2.8) years to record the incidence of AAA events. The associations between PWS and PWRI with AAA events were assessed using Cox proportional hazard analyses. The ability of PWS and PWRI to reclassify the risk of AAA events compared to the initial AAA diameter was examined using net reclassification index (NRI) and classification and regression tree (CART) analysis. RESULTS: After adjusting for other risk factors, one standard deviation increase in PWS (hazard ratio, HR, 1.56, 95% confidence intervals, CI 1.19, 2.06; p = 0.001) and PWRI (HR 1.74, 95% CI 1.29, 2.34; p < 0.001) were associated with significantly higher risks of AAA events. In the CART analysis, PWRI was identified as the best single predictor of AAA events at a cut-off value of > 0.562. PWRI, but not PWS, significantly improved the classification of risk of AAA events compared to the initial AAA diameter alone. CONCLUSION: PWS and PWRI predicted the risk of AAA events but only PWRI significantly improved the risk stratification compared to aortic diameter alone. KEY POINTS: • Aortic diameter is an imperfect measure of abdominal aortic aneurysm (AAA) rupture risk. • This observational study of 210 participants found that peak wall stress (PWS) and peak wall rupture index (PWRI) predicted the risk of aortic rupture or AAA repair. • PWRI, but not PWS, significantly improved the risk stratification for AAA events compared to aortic diameter alone.

A quarter of a century biomechanical rupture risk assessment of abdominal aortic aneurysms. Achievements, clinical relevance, and ongoing developments.

Abdominal aortic aneurysm (AAA) disease, the local enlargement of the infrarenal aorta, is a serious condition that causes many deaths, especially in men exceeding 65 years of age. Over the past quarter of a century, computational biomechanical models have been developed towards the assessment of AAA risk of rupture, technology that is now on the verge of being integrated within the clinical decision-making process. The modeling of AAA requires a holistic understanding of the clinical problem, in order to set appropriate modeling assumptions and to draw sound conclusions from the simulation results. In this article we summarize and critically discuss the proposed modeling approaches and report the outcome of clinical validation studies for a number of biomechanics-based rupture risk indices. Whilst most of the aspects concerning computational mechanics have already been settled, it is the exploration of the failure properties of the AAA wall and the acquisition of robust input data for simulations that has the greatest potential for the further improvement of this technology.

Biomechanical Assessment of Macro-Calcification in Human Carotid Atherosclerosis and Its Impact on Smooth Muscle Cell Phenotype.

Intimal calcification and vascular stiffening are predominant features of end-stage atherosclerosis. However, their role in atherosclerotic plaque instability and how the extent and spatial distribution of calcification influence plaque biology remain unclear. We recently showed that extensive macro calcification can be a stabilizing feature of late-stage human lesions, associated with a reacquisition of more differentiated properties of plaque smooth muscle cells (SMCs) and extracellular matrix (ECM) remodeling. Here, we hypothesized that biomechanical forces related to macro-calcification within plaques influence SMC phenotype and contribute to plaque stabilization. We generated a finite element modeling (FEM) pipeline to assess plaque tissue stretch based on image analysis of preoperative computed tomography angiography (CTA) of carotid atherosclerotic plaques to visualize calcification and soft tissues (lipids and extracellular matrix) within the lesions. Biomechanical stretch was significantly reduced in tissues in close proximity to macro calcification, while increased levels were observed within distant soft tissues. Applying this data to an in vitro stretch model on primary vascular SMCs revealed upregulation of typical markers for differentiated SMCs and contractility under low stretch conditions but also impeded SMC alignment. In contrast, high stretch conditions in combination with calcifying conditions induced SMC apoptosis. Our findings suggest that the load bearing capacities of macro calcifications influence SMC differentiation and survival and contribute to atherosclerotic plaque stabilization.

Patient-specific biomechanical analysis of atherosclerotic plaques enabled by histologically validated tissue characterization from computed tomography angiography: A case study.

BACKGROUND: Rupture of unstable atherosclerotic plaques with a large lipid-rich necrotic core and a thin fibrous cap cause myocardial infarction and stroke. Yet it has not been possible to assess this for individual patients. Clinical guidelines still rely on use of luminal narrowing, a poor indicator but one that persists for lack of effective means to do better. We present a case study demonstrating the assessment of biomechanical indices pertaining to plaque rupture risk non-invasively for individual patients enabled by histologically validated tissue characterization. METHODS: Routinely acquired clinical images of plaques were analyzed to characterize vascular wall tissues using software validated by histology (ElucidVivo, Elucid Bioimaging Inc.). Based on the tissue distribution, wall stress and strain were then calculated at spatial locations with varied fibrous cap thicknesses at diastolic, mean and systolic blood pressures. RESULTS: The von Mises stress of 152 [131, 172] kPa and the equivalent strain of 0.10 [0.08, 0.12] were calculated where the fibrous cap thickness was smallest (560 µm) (95% CI in brackets). The stress at this location was at a level predictive of plaque failure. Stress and strain at locations with larger cap thicknesses were calculated to be lower, demonstrating a clinically relevant range of risk levels. CONCLUSION: Patient specific tissue characterization can identify distributions of stress and strain in a clinically relevant range. This capability may be used to identify high-risk lesions and personalize treatment decisions for individual patients with cardiovascular disease and improve prevention of myocardial infarction and stroke.

Effect of Telmisartan on the Peak Wall Stress and Peak Wall Rupture Index of Small Abdominal Aortic Aneurysms: An Exploratory Analysis of the TEDY Trial.

OBJECTIVE: This study was an unplanned exploratory analysis of a subset of participants from the Telmisartan in the Management of Abdominal Aortic Aneurysm (TEDY) trial. It aimed to assess the efficacy of the angiotensin 1 receptor blocker telmisartan in reducing abdominal aortic aneurysm (AAA) peak wall stress (PWS) and peak wall rupture index (PWRI) among individuals with small AAAs. METHODS: Participants with AAAs measuring 35 - 49 mm in maximum diameter were randomised to receive telmisartan 40 mg or identical placebo in the TEDY trial. Participants who had computed tomography angiography performed at entry and at least one other time point during the trial (12 or 24 months) were included in the current study. Orthogonal AAA diameter, PWS, and PWRI were measured using previously validated methods. The annual change in PWS and PWRI from baseline was compared between participants allocated telmisartan or placebo using linear mixed effects models. These models were either unadjusted or adjusted for risk factors that were different in the groups at entry (p < .100) or systolic blood pressure (SBP) at one year. RESULTS: Of the 207 participants recruited to TEDY, 124 were eligible for inclusion in this study. This study included 65 and 59 participants from the telmisartan and placebo groups, respectively. The PWS and PWRI were not significantly different in the two groups at baseline. Participants allocated telmisartan had a slower annual increase in PWS (-4.19; 95% CI -8.24, -0.14 kPa/year; p = .043) and PWRI (-0.014; 95% CI -0.026, -0.001; p = .032) compared with those allocated placebo after adjusting for risk factors. After adjustment for SBP at one year, telmisartan did not significantly reduce annual increases in PWS or PWRI. CONCLUSION: The findings of this study suggest that telmisartan limits the rate of increase in PWS and PWRI of small AAAs by reducing blood pressure.

Geometric and biomechanical modeling aided by machine learning improves the prediction of growth and rupture of small abdominal aortic aneurysms.

It remains difficult to predict when which patients with abdominal aortic aneurysm (AAA) will require surgery. The aim was to study the accuracy of geometric and biomechanical analysis of small AAAs to predict reaching the threshold for surgery, diameter growth rate and rupture or symptomatic aneurysm. 189 patients with AAAs of diameters 40-50 mm were included, 161 had undergone two CTAs. Geometric and biomechanical variables were used in prediction modelling. Classifications were evaluated with area under receiver operating characteristic curve (AUC) and regressions with correlation between observed and predicted growth rates. Compared with the baseline clinical diameter, geometric-biomechanical analysis improved prediction of reaching surgical threshold within four years (AUC 0.80 vs 0.85, p = 0.031) and prediction of diameter growth rate (r = 0.17 vs r = 0.38, p = 0.0031), mainly due to the addition of semiautomatic diameter measurements. There was a trend towards increased precision of volume growth rate prediction (r = 0.37 vs r = 0.45, p = 0.081). Lumen diameter and biomechanical indices were the only variables that could predict future rupture or symptomatic AAA (AUCs 0.65-0.67). Enhanced precision of diameter measurements improves the prediction of reaching the surgical threshold and diameter growth rate, while lumen diameter and biomechanical analysis predicts rupture or symptomatic AAA.

Systematic Review and Meta-Analysis of Peak Wall Stress and Peak Wall Rupture Index in Ruptured and Asymptomatic Intact Abdominal Aortic Aneurysms.

Background Prior studies have suggested aortic peak wall stress (PWS) and peak wall rupture index (PWRI) can estimate the rupture risk of an abdominal aortic aneurysm (AAA), but whether these measurements have independent predictive ability over assessing AAA diameter alone is unclear. The aim of this systematic review was to compare PWS and PWRI in participants with ruptured and asymptomatic intact AAAs of similar diameter. Methods and Results Web of Science, Scopus, Medline, and The Cochrane Library were systematically searched to identify studies assessing PWS and PWRI in ruptured and asymptomatic intact AAAs of similar diameter. Random-effects meta-analyses were performed using inverse variance-weighted methods. Leave-one-out sensitivity analyses were conducted to assess the robustness of findings. Risk of bias was assessed using a modification of the Newcastle-Ottawa scale and standard quality assessment criteria for evaluating primary research papers. Seven case-control studies involving 309 participants were included. Meta-analyses suggested that PWRI (standardized mean difference, 0.42; 95% CI, 0.14-0.70; P=0.004) but not PWS (standardized mean difference, 0.13; 95% CI, -0.18 to 0.44; P=0.418) was greater in ruptured than intact AAAs. Sensitivity analyses suggested that the findings were not dependent on the inclusion of any single study. The included studies were assessed to have a medium to high risk of bias. Conclusions Based on limited evidence, this study suggested that PWRI, but not PWS, is greater in ruptured than asymptomatic intact AAAs of similar maximum aortic diameter.

Virtual Transcriptomics: Noninvasive Phenotyping of Atherosclerosis by Decoding Plaque Biology From Computed Tomography Angiography Imaging.

[Figure: see text].

Pliable, Scalable, and Degradable Scaffolds with Varying Spatial Stiffness and Tunable Compressive Modulus Produced by Adopting a Modular Design Strategy at the Macrolevel.

Clinical results obtained when degradable polymer-based medical devices are used in breast reconstruction following mastectomy are promising. However, it remains challenging to develop a large scaffold structure capable of providing both sufficient external mechanical support and an internal cell-like environment to support breast tissue regeneration. We propose an internal-bra-like prototype to solve both challenges. The design combines a 3D-printed scaffold with knitted meshes and electrospun nanofibers and has properties suitable for both breast tissue regeneration and support of a silicone implant. Finite element analysis (FEA) was used to predict the macroscopic and microscopic stiffnesses of the proposed structure. The simulations show that introduction of the mesh leads to a macroscopic scaffold stiffness similar to the stiffness of breast tissue, and mechanical testing confirms that the introduction of more layers of mesh in the modular design results in a lower elastic modulus. The compressive modulus of the scaffold can be tailored within a range from hundreds of kPa to tens of kPa. Biaxial tensile testing reveals stiffening with increasing strain and indicates that rapid strain-induced softening occurs only within the first loading cycle. In addition, the microscopic local stiffness obtained from FEA simulations indicates that cells experience significant heterogeneous mechanical stimuli at different places in the scaffold and that the local mechanical stimulus generated by the strand surface is controlled by the elastic modulus of the polymer, rather than by the scaffold architecture. From in vitro experiments, it was observed that the addition of knitted mesh and an electrospun nanofiber layer to the scaffold significantly increased cell seeding efficiency, cell attachment, and proliferation compared to the 3D-printed scaffold alone. In summary, our results suggest that the proposed design strategy is promising for soft tissue engineering of scaffolds to assist breast reconstruction and regeneration.

Subject-specific FE models of the human femur predict fracture path and bone strength under single-leg-stance loading.

Hip fractures are a major health problem with high socio-economic costs. Subject-specific finite element (FE) models have been suggested to improve the fracture risk assessment, as compared to clinical tools based on areal bone mineral density, by adding an estimate of bone strength. Typically, such FE models are limited to estimate bone strength and possibly the fracture onset, but do not model the fracture process itself. The aim of this study was to use a discrete damage approach to simulate the full fracture process in subject-specific femur models under stance loading conditions. A framework based on the partition of unity finite element method (PUFEM), also known as XFEM, was used. An existing PUFEM framework previously used on a homogeneous generic femur model was extended to include a heterogeneous material description together with a strain-based criterion for crack initiation. The model was tested on two femurs, previously mechanically tested in vitro. Our results illustrate the importance of implementing a subject-specific material distribution to capture the experimental fracture pattern under stance loading. Our models accurately predicted the fracture pattern and bone strength (1% and 5% error) in both investigated femurs. This is the first study to simulate complete fracture paths in subject-specific FE femur models and it demonstrated how discrete damage models can provide a more complete picture of fracture risk by considering both bone strength and fracture toughness in a subject-specific fashion.

Biomechanical indices are more sensitive than diameter in predicting rupture of asymptomatic abdominal aortic aneurysms.

OBJECTIVE: Several studies of biomechanical rupture risk assessment (BRRA) showed its advantage over the diameter criterion in rupture risk assessment of abdominal aortic aneurysm (AAA). However, BRRA studies have not investigated the predictability of biomechanical risk indices at different time points ahead of rupture, nor have they been performed blinded for biomechanical analysts. The objective of this study was to test the predictability of the BRRA method against diameter-based risk indices in a quasi-prospective patient cohort study. METHODS: In total, 12 women and 31 men with intact AAAs at baseline have been selected retrospectively at two medical centers. Within 56 months, 19 cases ruptured, whereas 24 cases remained intact within 2 to 56 months. This outcome was kept confidential until all biomechanical activities in this study were finished. The biomechanical AAA rupture risk was calculated at baseline using high-fidelity and low-fidelity finite element method models. The capability of biomechanics-based and diameter-based risk indices to predict the known outcomes at 1 month, 3 months, 6 months, 9 months, and 12 months after baseline was validated. Besides common cohort statistics, the area under the curve (AUC) of receiver operating characteristic curves has been used to grade the different rupture risk indices. RESULTS: Up to 9 months ahead of rupture, the receiver operating characteristic analysis of biomechanics-based risk indices showed a higher AUC than diameter-based indices. Six months ahead of rupture, the largest difference was observed with an AUC of 0.878 for the high-fidelity biomechanical risk index, 0.859 for the low-fidelity biomechanical risk index, 0.789 for the diameter, and 0.821 for the sex-adjusted diameter. In predictions beyond 9 months, none of the risk indices proved to be superior. CONCLUSIONS: High-fidelity biomechanical modeling improves the predictability of AAA rupture. Asymptomatic AAA patients with high biomechanical AAA rupture risk indices have an increased risk of rupture. Integrating biomechanics-based diagnostic indices may significantly decrease the false-positive rate in AAA treatment. CLINICAL RELEVANCE: Rupture of abdominal aortic aneurysm (AAA) is the tenth leading cause of death in men older than 60 years; however, the currently used maximal diameter criterion has a high false-positive rate. In this study, we have compared this criterion with biomechanical rupture risk assessment on the unique data set of 43 asymptomatic AAAs, of which 19 ruptured later. Moreover, the AAA outcome was blinded to the operator for the first time. Our data demonstrated that the biomechanical rupture risk assessment is superior to maximal diameter in predicting AAA rupture up to 9 months ahead and significantly decreases the false-positive rate.

Systematic review and meta-analysis of the association between intraluminal thrombus volume and abdominal aortic aneurysm rupture.

BACKGROUND: Intraluminal thrombus (ILT) is present in most abdominal aortic aneurysms (AAAs), although its role in AAA progression is controversial. METHODS: A literature search was performed to identify studies that investigated the association between ILT volume and AAA rupture. A study assessment tool was developed to assess the methodologic quality of included studies. A meta-analysis was conducted using an inverse variance-weighted random-effects model to compare the ILT volume in ruptured and asymptomatic intact AAAs. Leave-one-out sensitivity analyses were conducted to assess the robustness of the findings. A subanalysis was performed including studies in which patients with asymptomatic intact and ruptured AAAs were matched for aortic diameter. Interstudy heterogeneity was assessed using the I2 statistic. RESULTS: Eight studies involving 672 patients were included in this systematic review. Meta-analysis of all studies found a greater ILT volume in patients with ruptured AAAs than in patients with asymptomatic intact AAAs (standardized mean difference, 0.56; 95% confidence interval, 0.17-0.96; P = .005; I2 = 79.8%). Sensitivity analyses suggested that the findings were robust; however, aortic diameter was significantly larger in ruptured than in asymptomatic intact AAAs (mean ± standard deviation, 78 ± 18 and 64 ± 15 mm, respectively; P < .001). In the subanalysis of studies that matched for diameter, no significant difference in ILT volume between groups was found (standardized mean difference, 0.03; 95% confidence interval, -0.27 to 0.33; P = .824; I2 = 0%). CONCLUSIONS: This meta-analysis suggests that ILT volume is greater in patients with ruptured AAAs than in patients with asymptomatic intact AAAs, although this is most likely due to the larger diameter of ruptured AAAs.

A large proportion of patients with small ruptured abdominal aortic aneurysms are women and have chronic obstructive pulmonary disease.

OBJECTIVE: In a population-based cohort of ruptured abdominal aortic aneurysms (rAAAs), our aim was to investigate clinical, morphological and biomechanical features in patients with small rAAAs. METHODS: All patients admitted to an emergency department in Stockholm and Gotland, a region with a population of 2.1 million, between 2009-2013 with a CT-verified rupture (n = 192) were included, and morphological measurements were performed. Patients with small rAAAs, maximal diameter (Dmax) ≤ 60 mm were selected (n = 27), and matched 2:1 by Dmax, sex and age to intact AAA (iAAAs). For these patients, morphology including volume and finite element analysis-derived biomechanics were assessed. RESULTS: The mean Dmax for all rAAAs was 80.8 mm (SD = 18.9 mm), women had smaller Dmax at rupture (73.4 ± 18.4 mm vs 83.1 ± 18.5 mm, p = 0.003), and smaller neck and iliac diameters compared to men. Aortic size index (ASI) was similar between men and women (4.1 ± 3.1 cm/m2 vs 3.8 ± 1.0 cm/m2). Fourteen percent of all patients ruptured at Dmax ≤ 60 mm, and a higher proportion of women compared to men ruptured at Dmax ≤ 60 mm: 27% (12/45) vs. 10% (15/147), p = 0.005. Also, a higher proportion of patients with a chronic obstructive pulmonary disease ruptured at Dmax ≤ 60 mm (34.6% vs 14.6%, p = 0.026). Supra-renal aortic size index (14.0, IQR 13.3-15.3 vs 12.8, IQR = 11.4-14.0) and peak wall rupture index (PWRI, 0.35 ± 0.08 vs 0.43 ± 0.11, p = 0.016) were higher for small rAAAs compared to matched iAAAs. Aortic size index, peak wall stress and aneurysm volume did not differ. CONCLUSION: More than one tenth of ruptures occur at smaller diameters, women continuously suffer an even higher risk of presenting with smaller diameters, and this must be considered in surveillance programs. The increased supra-renal aortic size index and PWRI are potential markers for rupture risk, and patients under surveillance with these markers may benefit from increased attention, and potentially from timely repair.

Aortic Lumen Area Is Increased in Ruptured Abdominal Aortic Aneurysms and Correlates to Biomechanical Rupture Risk.

PURPOSE: To investigate how 2-dimensional geometric parameters differ between ruptured and asymptomatic abdominal aortic aneurysms (AAAs) and provide a biomechanical explanation for the findings. METHODS: The computed tomography angiography (CTA) scans of 30 patients (mean age 77±10 years; 23 men) with ruptured AAAs and 60 patients (mean age 76±8 years; 46 men) with asymptomatic AAAs were used to measure maximum sac diameter along the center lumen line, the cross-sectional lumen area, the total vessel area, the intraluminal thrombus (ILT) area, and corresponding volumes. The CTA data were segmented to create 3-dimensional patient-specific models for finite element analysis to compute peak wall stress (PWS) and the peak wall rupture index (PWRI). To reduce confounding from the maximum diameter, 2 diameter-matched groups were selected from the initial patient cohorts: 28 ruptured AAAs and another with 15 intact AAAs (diameters 74±12 vs 73±11, p=0.67). A multivariate model including the maximum diameter, the lumen area, and the ILT area of the 60 intact aneurysms was employed to predict biomechanical rupture risk parameters. RESULTS: In the diameter-matched subgroup comparison, ruptured AAAs had a significantly larger cross-sectional lumen area (1954±1254 vs 1120±623 mm2, p=0.023) and lower ILT area ratio (55±24 vs 68±24, p=0.037). The ILT area (2836±1462 vs 2385±1364 mm2, p=0.282) and the total vessel area (3956±1170 vs 4338±1388 mm2, p=0.384) did not differ statistically between ruptured and intact aneurysms. The PWRI was increased in ruptured AAAs (0.80 vs 0.48, p<0.001), but the PWS was similar (249 vs 284 kPa, p=0.194). In multivariate regression analysis, lumen area was significantly positively associated with both PWS (p<0.001) and PWRI (p<0.01). The ILT area was also significantly positively associated with PWS (p<0.001) but only weakly with PWRI (p<0.01). The lumen area conferred a higher risk increase in both PWS and PWRI when compared with the ILT area. CONCLUSION: The lumen area is increased in ruptured AAAs compared to diameter-matched asymptomatic AAAs. Furthermore, this finding may in part be explained by a relationship with biomechanical rupture risk parameters, in which lumen area, irrespective of maximum diameter, increases PWS and PWRI. These observations thus suggest a possible method to improve prediction of rupture risk in AAAs by measuring the lumen area without the use of computational modeling.

Neutrophil Elastase-Derived Fibrin Degradation Products Indicate Presence of Abdominal Aortic Aneurysms and Correlate with Intraluminal Thrombus Volume.

BACKGROUND: The intraluminal thrombi (ILT) of abdominal aortic aneurysms (AAA) contain neutrophils, which can secrete elastase. We evaluated whether plasma neutrophil elastase-derived cross-linked fibrin degradation products (E-XDP) could reveal the presence, size and mechanical stress of AAAs and its ILTs. METHODS: E-XDP and D-dimer were measured in plasma from 37 male patients with AAA and 42 male controls. The ILT volumes of the AAAs and any coexisting aneurysms could be measured in 29 patients and finite element analysis was performed to estimate mechanical stress of the ILT. E-XDP, neutrophil elastase and neutrophil marker CD66acd were evaluated in aortic tissue with immunohistochemistry (IHC). The association between ILT volume and E-XDP was validated in a separate cohort (n = 51). RESULTS: E-XDP levels were elevated in patients with AAA compared with controls (p = 5.8e-13), indicated AAA with 98% sensitivity, 86% specificity and increased with presence of coexisting aneurysms. The association between AAA and increased E-XDP was independent of smoking, comorbidities and medication. E-XDP correlated with volume of all ILTs (r = 0.76, p = 4.5e-06), mean ILT stress (r = 0.46, p = 0.013) and the volume of the AAA-associated ILT (r = 0.64, p = 0.00017). E-XDP correlated stronger with ILT volume compared with D-dimer (r = 0.76 vs. r = 0.64, p = 0.018). The correlation between E-XDP and ILT volume was validated in the separate cohort (r = 0.53, p = 7.6e-05). IHC revealed E-XDP expression in the ILT, spatially related to neutrophil elastase and neutrophils. CONCLUSION: E-XDP is a marker of the presence of AAA and coexisting aneurysms as well as the volume and mechanical stress of the ILT.