Abdominal Aortic Aneurysm Morphology Research Articles

Morphology of Abdominal Aortic Aneurysms and Correlation with Biomechanical Tests of Aneurysmal Wall Fragments

Evaluate how specific morphologic aspects of abdominal aortic aneurysms (AAAs), including asymmetries, curvatures, tortuosities, and angulations, among others can influence the intrinsic biomechanical properties of the AAA's wall. This study analyzed the correlation of geometric measurements (1-dimensional, 2-dimensional, and 3-dimensional) of preoperative tomographic images of AAA with uniaxial biomechanical tests of the arterial wall fragments of these AAA obtained in open surgical repair of aneurysms. It was a multicenter, experimental, and observational study, and initially 54 individuals were selected who underwent open surgical of AAA, with valid biomechanical tests of the anterior wall of the AAA. Seven individuals were excluded because they had poor preoperative quality computed tomography scans and/or artifacts that impeded image segmentation and extraction of AAA geometric indices. The aortic fragments were subjected to uniaxial biomechanical destructive tests to obtain the following data: maximum load, failure stress, failure tension, failure strain energy, strain, and fragment thickness. In the same patients, preoperative computed tomography scans were performed with the extraction of 26 geometric indices, subdivided into 9 1-dimensional indices, 6 2-dimensional indices, and 11 3-dimensional indices. Data were subjected to statistical analysis using SPSS version28. Comparing ruptured and unruptured AAA, no statistical difference was observed between the biomechanical and geometric parameters. The fragment thickness of the ruptured AAA was lower than that of the unruptured AAA (P<0.05). By comparing tomographic geometric indices and biomechanical parameters of the aortic fragments using Pearson's coefficient, positive and linear correlations (P<0.05) were observed between the geometric variable maximum diameter (Dmax) of the AAA with maximum load (r=0.408), failure tension (r=0.372), and failure stress (r=0.360). Positive and linear correlations were also observed between the variable diameter/height ratio (DHr) and the maximum load (r=0.360), failure tension (r=0.354), and failure stress (r=0.289). The geometric variable DHr was dependent and correlated with Dmax. Simple regression analysis showed that R2 varied between 8.3% and 16.7%, and all models were significant (P<0.05). Dmax and DHr were linearly and positively correlated with the resistance parameters (maximum load, failure tension, and failure stress) of the AAA fragments. The DHr variable is dependent and correlated with Dmax. There was no correlation between the other geometric indices and the biomechanical parameters of the AAA wall. The asymmetries did not globally influence the biomechanics of AAA wall; however, they may influence regionally. Larger AAAs were stronger than smaller ones. Therefore, such findings may point toward Dmax is still the main geometric parameter, which influences the anterior wall, and possibly globally in the AAA.

Impact of Type 2 endoleaks on abdominal aortic aneurysm morphology

Impact of Type 2 endoleaks on abdominal aortic aneurysm morphology

Abdominal Aortic Aneurysm Morphology in the Chinese Population and Endovascular Aortic Aneurysm Repair Eligibility

Introduction: The current commercial endovascular abdominal aortic stent grafts are designed based on the anatomical data from the Western population. Objective: To investigate the morphological features of abdominal aortic aneurysm (AAA) in a Chinese cohort and its clinical implications. Methods: It was a retrospective, observational study. The preoperative computed tomography angiogram (CTAs) of patients who underwent endovascular aortic aneurysm repair (EVAR) from January 01, 2015 to December 31, 2020, were analyzed. A predefined set of AAA morphological measurements was taken. The eligibility of EVAR with current commercially available stent grafts on the market was examined. Results: A total of 210 cases were studied. The mean AAA diameter was 64.3 mm. The mean proximal and distal neck diameters were 22.9 mm and 24.4 mm, respectively, whereas the mean neck length was 23.8 mm and the mean infra-renal angle was 51.6°. The right and left mean common iliac arteries (CIAs) diameters were 21.2 mm and 18.3 mm. The right and left mean CIA lengths were 35.7 mm and 37.3 mm. The mean external iliac artery (EIA) diameter was 8.3 mm bilaterally. Female gender was associated with significantly smaller neck diameters, smaller EIA diameters, and larger infra-renal angle. EVAR eligibility ranged from 16%–37% and was significantly lower in females. Conclusions: The majority of Chinese patients with AAA did not meet the anatomical eligibility for EVAR, with neck angulation being the major deterrent. Female patients posed an additional anatomical challenge due to larger infra-renal angle and smaller iliac access diameter. The development of low-profile angulated neck-compatible EVAR devices may expand EVAR applicability in future.

Perfusion pressure of elastase impacts the formation ratio and diameters of abdominal aortic aneurysms in rats.

Intra-arterial perfusion with elastase is a common method used to create abdominal aortic aneurysms (AAA) models. The present study aimed to explore the impact of porcine pancreatic elastase (PPE) perfusion pressure on the morphology of abdominal aortic aneurysms. A total of 40 male Sprague Dawley rats were randomized into four groups. The elastase was perfused at pressures in the aortic lumen of 300, 100 and 0 mmHg in three groups, respectively. Rats perfused with saline at 300 mmHg were used as controls. The maximum diameters of the AAA were monitored with ultrasound at 7, 14 and 28 days after the operation. Elastin degradation and inflammatory cell counts were determined using histochemical staining. All rats were successfully perfused at the scheduled pressure. After 7 days, the AAA formation ratio of PPE-300, PPE-100 and PPE-0 was 100, 50 and 0%, respectively. After 14 days, the AAA formation ratio in PPE-100 and PPE-0 reached 90 and 20%, respectively. After 28 days, the diameters of the isolated aorta in PPE-300, PPE-100, PPE-0 and NaCl-300 were (mean ± standard deviation) 7.34±1.81, 4.02±0.40, 2.92±0.32 and 2.49±0.07 mm, respectively, and the difference between groups was statistically significant (P<0.05). The formation ratio in PPE-300, PPE-100, PPE-0 and NaCl-300 was 100, 100, 20 and 0%, respectively. Elastase perfusion pressure could impact the AAA formation ratio at an early stage and the maximum diameter of the aneurysm without increasing animal mortality. Elastase perfusion with high pressure could accelerate aneurysm formation and represents a potential method for building large-size abdominal aortic aneurysms. However, the underlying mechanisms need further investigation.

Abdominal Aortic Aneurysm Morphology as an Essential Criterion for Stratifying the Risk of Aneurysm Rupture.

The current stratification model of aneurysm rupture seems to be insufficient in some clinical cases. In our study, we determined the differences in wall structure between ruptured and unruptured aneurysms. We obtained computed tomography angiograms and categorized them into the following three groups, consisting of 49 patients each: the group with ruptured abdominal aortic aneurysms (rAAA), symptomatic (sAAA), and asymptomatic (aAAA). The three-dimensional AAA anatomy was digitally reconstructed for each patient through semi-automatically obtained segmentation, and each aneurysm was distinguished by the following three parameters: AFL (aneurysm flow lumen), ILT (intraluminal thrombus), and calcifications. The AFL volume was greater in rAAA compared with aAAA (p = 0.004), the ILT volume was greater in aAAA than in rAAA (p = 0.013), and the AFL/ILT surface ratio was bigger in rAAA than in aAAA (p < 0.001), sAAA than in aAAA (p = 0.033), and rAAA than in sAAA (p = 0.016). AFL/ILT surface*100 was defined as an independent predictive factor of rAAA to aAAA (OR 1.187; 95% CI 1.099–1.281), to sAAA (OR 1.045; 95% CI 1.004–1.087), and in sAAA vs. aAAA (OR 1.067; 95% CI 1.017–1.119). Consequently, the wall of rAAA differs significantly from unruptured aneurysms. The AFL/ILT surface ratio might indicate an increased risk of aneurysm rupture and the occurrence of symptoms in AAA.

Can We Still Teach Open Repair of Abdominal Aortic Aneurysm in The Endovascular Era? Single-Center Analysis on The Evolution of Procedural Characteristics Over 15 Years

In many vascular centers an endovascular first policy for the treatment of abdominal aortic aneurysms (AAA) has resulted in endovascular aortic repair (EVAR) outnumbering open aortic repair (OAR). The declining routine in OAR raises the question whether this might influence procedural outcomes and diminish surgical expertise for current and future vascular surgeons. We aimed to analyze OAR outcomes, AAA morphology and procedural details over the past 15 years while an endovascular first approach was successively implemented. All patients operated for (i)ntact infra-/juxtarenal AAA between January 1, 2005 and December 31, 2019 were identified. Outcome parameters were length of stay (hospital/ICU), in-hospital mortality and medical/surgical complications. Operative details were clamping zone, access and graft configuration. AAA anatomy including neck and iliac parameters was analyzed with Endosize©. Logistic regression, uni- and multivariate analysis were applied. 293 patients received elective OAR for iAAA. Baseline characteristics (age, sex, hypertension, smoking, occlusive disease, coronary disease, hyperlipidemia, diabetes, renal insufficiency and obesity) did not change over time. The number of OAR dropped significantly (-0.5 cases/year p = 0.02). The procedure time (2005-2007: 192.2 ± 87.5min to 2017-2019: 235.6 ± 88.2min; p = 0.0001) and the length of stay (2005-2007: 12.0 ± 7.9 to 2017-2019: 17.0 ± 23.1; p = 0.03) increased significantly, whereas the in-hospital mortality, length of ICU stay and complication rates didn't, nor did AAA anatomy. Upon multivariate analysis, annual number of OAR and any additional anastomosis significantly influenced procedure time, trainee involvement, for example, did not. Hospital length-of-stay depended on patient age (p = 0.002), complication rates (p < 0.0001) and procedure time (p = 0.006). Mortality and complication rates for OAR have remained low and constant. With the increase of EVAR, the absolute number of OARs has decreased significantly. However, the total procedure time has increased and depends significantly on the annual number of OARs in total and per surgeon. This might influence outcome parameters and should be implanted in future surgical education.

The risk of rupture and abdominal aortic aneurysm morphology: A computational study.

Prediction of rupture and optimal timing for abdominal aortic aneurysm (AAA) surgical intervention remain wanting even after decades of clinical, histological, and numerical research. Although studies estimating rupture from AAA geometrical features from CT imaging showed some promising results, they are still not being used in practice. Patient-specific numerical stress analysis introduced too many assumptions about wall structure for the related rupture potential index (RPI) to be considered reliable. Growth and remodeling (G&R) numerical models eliminate some of these assumptions and thus might have the most potential to calculate mural stresses and RPI and increase our understanding of rupture. To recognize numerical models as trustworthy, it is necessary to validate the computed results with results derived from imaging. Elastin degradation function is one of the main factors that determine idealized aneurysm sac shape. Using a hundred different combinations of variables defining AAA geometry or influences AAA stability (elastin degradation function parameters, collagen mechanics, and initial healthy aortic diameters), we investigated the relationship between AAA morphology and RPI and compared numerical results with clinical findings. Good agreement of numerical results with clinical expectations from the literature gives us confidence in the validity of the numerical model. We show that aneurysm morphology significantly influences the stability of aneurysms. Additionally, we propose new parameters, geometrical rupture potential index (GRPI) and normalized aneurysm length (NAL), that might predict rupture of aneurysms without thrombus better than currently used criteria (i.e., maximum diameter and growth rate). These parameters can be computed quickly, without the tedious processing of CT images.

High-Frequency Three-Dimensional Lumen Volume Ultrasound Is a Sensitive Method to Detect Early Aneurysmal Change in Elastase-Induced Murine Abdominal Aortic Aneurysm.

Objective The aim of this study was to investigate the reproducibility of anterior–posterior diameter (APd max ) and three-dimensional lumen volume (3DLV) measurements of abdominal aortic aneurysms (AAA) in a classical murine AAA model. We also compared the magnitude of change in the aortic size detected with each method of assessment. Methods Periadventitial application of porcine pancreatic elastase (PPE AAA) or sham surgery was performed in two cohorts of mice. Cohort 1 was used to assess for observer variability with the APd max and 3DLV measurements. Cohort 2 highlighted the relationship between APd max and 3DLV and changes in AAA detected. Results There was no significant observer variability detected with APd max measurement. Similarly, no significant intraobserver variability was evident with 3DLV; however, a small but significant interobserver difference was present. APd max and 3DLV measurements of PPE AAA significantly correlated. However, changes in the AAA morphology were detected earlier with 3DLV. Conclusion APd max and 3DLV are both reliable methods for measuring an AAA. Both these methods correlate with each other. However, changes in AAA morphology were detected earlier with 3DLV, which is important to detect subtle but important changes to aortic geometry in a laboratory setting. 3DLV measurement of AAA is a simple, reproducible, and comprehensive method for assessing changes in disease morphology.

Statistical techniques for predicting rupture risk in abdominal aortic aneurysms: A contribution based on bootstrap.

The morphometry of abdominal aortic aneurysms (AAA) has been recognized as one of the main factors that may predispose them to rupture. The need to quantify the morphometry of AAA on a patient-specific basis constitutes a valuable tool for assisting in rupture risk prediction. Previous results of this research group have determined the correlations between hemodynamic stresses and aneurysm morphometry by means of the Pearson coefficient. The present work aims to find how the AAA morphology correlates with the hemodynamic stresses acting on the arterial wall. To do so, the potential of the bootstrap technique has been explored. Bootstrap works appropriately in applications where few data are available (13 patient-specific AAA models were simulated). The methodology developed can be considered a contribution to predicting the hemodynamic stresses from the size and shape indices. The present work explores the use of a specific statistical technique (the bootstrap technique) to predict, based on morphological correlations, the patient-specific aneurysm rupture risk, provide greater understanding of this complex phenomenon that can bring about improvements in the clinical management of aneurysmatic patients. The results obtained using the bootstrap technique have greater reliability and robustness than those obtained by regression analysis using the Pearson coefficient, thus allowing to obtain more reliable results from the characteristics of the samples used, such as their small size and high variability. Additionally, it could be an indicator that other indices, such as AAA length, deformation rate, saccular index, and asymmetry, are important.

A comparison of subjective clinical and objective judgement of abdominal aortic aneurysm morphology

Background We compared the subjective, clinical judgement of morphology with the objective judgement of mechanical structural analysis. Methods Using structural analysis with the finite element method, we previously created a model of abdominal aortic aneurysm (AAA) that visualized the distribution of the maximum principal stress (MPS) in the aortic wall and identified the area of prominent stress. AAA morphology was determined according to the area showing MPS>0.03 MPa. AAAs with low aspect ratio (horizontally long AAA sac) and small fillet radius were defined as saccular. Twelve vascular surgeons were recruited. First, they judged the AAA as saccular or fusiform with 3-dimensional images at their clinical impression (subjective eyeball judgement). Second, they applied the deformable figure tools on the AAA-shaped sagittal view in the application model for 30 AAA cases. From the data of the tools applied, the mechanical structural analysis was performed semi-automatically and the morphology was judged with the objective simple application. Results The structural analysis revealed that only one case was judged as saccular by 11 out of 12 surgeons and the other 29 AAAs were judged as fusiform by two-thirds or more of the surgeons. In contrast, 5 cases were subjectively judged as saccular by eight and more of the surgeons. Conclusions The clinical judgement of AAA saccular morphology by the vascular surgeons was different from the judgement derived from the mechanical structural analysis using the application model. The saccular morphology may be theoretically rare in AAAs.

A machine leaning approach for abdominal aortic aneurysm severity assessment using geometric, biomechanical, and patient-specific historical clinical features.

Recent studies monitoring severity of abdominal aortic aneurysm (AAA) suggested that reliance on only the maximum transverse diameter ( D max ) may be insufficient to predict AAA rupture risk. Moreover, geometric indices, biomechanical parameters, material properties, and patient-specific historical data affect AAA morphology, indicating the need for an integrative approach that incorporates all factors for more accurate estimation of AAA severity. We implemented a machine learning algorithm using 45 features extracted from 66 patients. The model was generated using the J48 decision tree algorithm with the aim of maximizing model accuracy. Three different feature sets were used to assess the prediction rate: i) using D max as a single-feature set, ii) using a set of all features, and, lastly iii) using a feature set selected via the BestFirst feature selection algorithm. Our results indicate that BestFirst feature selection yielded the highest prediction accuracy. These results indicate that a combination of several specific parameters that comprehensively capture AAA behavior may enable a suitable assessment of AAA severity, suggesting the potential benefit of machine learning for this application.

Investigation of the observed rupture lines in abdominal aortic aneurysms using crack propagation simulations.

To use crack propagation simulation to study the rupture site characteristics in ruptured abdominal aortic aneurysms (AAA). Rupture lines were precisely documented in four ruptured AAA harvested whole from cadavers. Wall thickness and material parameters were experimentally determined. Using subject-specific 3D geometry and subject-specific finite elastic model parameters, crack propagation simulations were conducted based on basic fracture mechanics principles to investigate if and how localized weak spots may have led to the observed rupture lines. When an initial crack was imposed at the site of peak wall stress, the propagated path did not match the observed rupture line. This indicates that in this study population, the peak wall stress was unlikely to have caused the observed rupture. When cracks were initiated at random locations in the AAA along random orientations for random initial lengths, the orientation of the resulting propagated rupture line was consistently longitudinal. This suggests that the AAA morphology predisposes the AAA to rupture longitudinally, which is consistent with observations. It was found that, in this study population, rupture may have initiated at short segments of less than about 1 cm that then propagated to form the observed rupture lines. This suggests that ex vivo experimental and in vivo elastography studies should seek a spatial resolution (approx. 1 cm) to reliably identify weak spots in AAA. The small study population and lack of a reliable failure model for AAA tissue make these findings preliminary.

The Relationship Between Serum Interleukin-1α and Asymptomatic Infrarenal Abdominal Aortic Aneurysm Size, Morphology, and Growth Rates

In a pilot study, a relationship between abdominal aortic aneurysm (AAA) diameter and serum interleukin (IL)-1α levels was reported, and that endothelial cell (EC) activation invitro in response to serum from patients with AAA was blocked by anti-IL-1α antibodies. The aim of the present study was to further investigate the relationship between serum IL-1α and asymptomatic infrarenal AAA size, morphology, and growth rates. Serum IL-1α was measured using enzyme linked immunosorbent assay in 101 patients with asymptomatic, infrarenal AAA and related to aneurysm size, morphology, and growth rates. IL-1α was measured in 101 patients. There was no statistically significant difference in mean age between men and women. IL-1α was detectable in 62.4% of patients; median IL-1α titre was 3.26pg/mL. There was no statistically significant relationship between IL-1α and maximum AAA antero-posterior diameter as measured by ultrasound (p=.649), AAA morphology (aortic length [p=.394], sac [p=.369], and thrombus volume [p=.629]) as measured on computed tomography, absolute increase in AAA diameter (p=.214), or AAA growth rate (p=.230). IL-1α is detectable in the majority of patients with infrarenal AAA, but the cause and clinical significance of this novel observation remains unknown.

Predicting reinterventions after open and endovascular aneurysm repair using the St George's Vascular Institute score

Identifying patients at risk for aneurysm rupture and sac expansion after open and endovascular abdominal aortic aneurysm (AAA) repair (EVAR) may help to attenuate this risk by intensifying follow-up and early detection of problems. The goal of this study was to validate the St George's Vascular Institute (SGVI) score to identify patients at risk for a secondary intervention after elective aneurysm repair. A post hoc on-treatment analysis of a randomized trial comparing open AAA repair and EVAR was performed. In this multicenter trial, 351 patients were randomly assigned to undergo open AAA repair or EVAR. Information on survival and reinterventions was available for all patients at 5years postoperatively, for 79% at 6years, and for 53% at 7years. Open repair was completed in 173 patients and EVAR in 171, based on an on-treatment analysis. Because 17 patients had incomplete anatomic data, 327 patients (157 open repair and 170 EVAR) were available for analysis. During 6years of follow-up, 78 patients underwent at least one reintervention. The SGVI score, which is calculated from preoperative AAA morphology using aneurysm and iliac diameter, predictively dichotomized patients into groups at high-risk or low-risk for a secondary intervention. The observed freedom from reintervention was compared between groups at predicted high-risk and predicted low-risk. The 20 patients in the high-risk group were indeed at higher risk for a secondary intervention compared with the 307 patients predicted to be at low risk (hazard ratio [HR], 3.82; 95% confidence interval [CI], 2.05-7.11; P< .001). Discrimination between high-risk and low-risk groups was valid for EVAR (HR, 4.06; 95% CI, 1.93-8.51; P< .001) and for open repair (HR, 3.41; 95% CI, 1.02-11.4; P= .033). The SGVI score appears to be a useful tool to predict reintervention risk in patients after open repair and EVAR.

Patient-specific analysis of displacement forces acting on fenestrated stent grafts for endovascular aneurysm repair

Treatment options for abdominal aortic aneurysm (AAA) include highly invasive open surgical repair or minimally invasive endovascular aneurysm repair (EVAR). Despite being minimally invasive, some patients are not suitable for EVAR due to hostile AAA morphology. Fenestrated-EVAR (F-EVAR) was introduced to address these limitations of standard EVAR, where AAA is treated using a Fenestrated Stent Graft (FSG). In order to assess durability of F-EVAR, displacement forces acting on FSGs were analysed in this study, based on patient-specific geometries reconstructed from computed tomography (CT) scans. The magnitude and direction of the resultant displacement forces acting on the FSG were numerically computed using computational fluid dynamics (CFD) with a rigid wall assumption. Although displacement force arises from blood pressure and friction due to blood flow, numerical simulations elucidated that net blood pressure is the dominant contributor to the overall displacement force; as a result, time dependence of the resultant displacement force followed pressure waveform very closely. The magnitude of peak displacement force varied from 1.9N to 14.3N with a median of 7.0N. A strong positive correlation was found between inlet cross-sectional area (CSA), anterior/posterior (A/P) angle and the peak displacement force i.e. as inlet CSA or A/P angle increases, the magnitude of resultant displacement increases. This study manifests that while loads exerted by the pulsatile flow dictates the cyclic variation of the displacement force, its magnitude depends not only on blood pressure but also the FSG morphology, with the latter determining the direction of the displacement force.

Comparison of fenestrated endografts and the snorkel/chimney technique

Recent approval by the Food and Drug Administration of custom fenestrated endografts has increased endovascular options for patients with short-neck or juxtarenal abdominal aortic aneurysms (AAAs). We sought to compare the early learning curve at a single institution of fenestrated repair vs the snorkel technique. From 2009 to 2013, we performed 57 consecutive snorkel procedures for juxtarenal AAAs in an Institutional Review Board-approved prospective cohort, and since the summer of 2012, we gained access to the Food and Drug Administration-approved custom fenestrated device. Patient demographics, imaging, and operative techniques were compared between the first 15 cases for each of the snorkel (sn-EVAR) and fenestrated (f-EVAR) endovascular aneurysm repair (EVAR) techniques. Patient demographics and AAA morphology on preoperative imaging were similar between the groups. Operative time tended to be similar in the 3- to 4-hour range, with more fluoroscopy time and less contrast material used in f-EVAR than in sn-EVAR (P< .05) because of differing strategies of renal premarking. Larger delivery systems for f-EVAR required a higher rate of iliac conduits (40% vs 0%). Perioperative complications, short-term renal patency rates, and evidence of acute kidney injury were similar. The early experience of f-EVAR was similar to that of sn-EVAR in terms of patient demographics, case selection, and procedural characteristics. A significant portion of the learning curve for both procedures, particularly for f-EVAR, lies in the preoperative planning of fenestrations and the cannulation of branch vessels. Similar short-term postoperative outcomes between these two particular techniques indicate that both will have utility in the treatment of high-risk patients with complex anatomy.

Familial abdominal aortic aneurysm is associated with more complications after endovascular aneurysm repair

A familial predisposition to abdominal aortic aneurysms (AAAs) is present in approximately one-fifth of patients. Nevertheless, the clinical implications of a positive family history are not known. We investigated the risk of aneurysm-related complications after endovascular aneurysm repair (EVAR) for patients with and without a positive family history of AAA. Patients treated with EVAR for intact AAAs in the Erasmus University Medical Center between 2000 and 2012 were included in the study. Family history was obtained by written questionnaire. Familial AAA (fAAA) was defined as patients having at least one first-degree relative affected with aortic aneurysm. The remaining patients were considered sporadic AAA. Cardiovascular risk factors, aneurysm morphology (aneurysm neck, aneurysm sac, and iliac measurements), and follow-up were obtained prospectively. The primary end point was complications after EVAR, a composite of endoleaks, need for secondary interventions, aneurysm sac growth, acute limb ischemia, and postimplantation rupture. Secondary end points were specific components of the primary end point (presence of endoleak, need for secondary intervention, and aneurysm sac growth), aneurysm neck growth, and overall survival. Kaplan-Meier estimates for the primary end point were calculated and compared using log-rank (Mantel-Cox) test of equality. A Cox-regression model was used to calculate the independent risk of complications associated with fAAA. A total of 255 patients were included in the study (88.6% men; age 72 ± 7 years, median follow-up 3.3 years; interquartile range, 2.2-6.1). A total of 51 patients (20.0%) were classified as fAAA. Patients with fAAA were younger (69 vs 72 years; P = .015) and were less likely to have ever smoked (58.8% vs 73.5%; P = .039). Preoperative aneurysm morphology was similar in both groups. Patients with fAAA had significantly more complications after EVAR (35.3% vs 19.1%; P = .013), with a twofold increased risk (adjusted hazard ratio, 2.1; 95% confidence interval, 1.2-3.7). Secondary interventions (39.2% vs 20.1%; P = .004) and aneurysm sac growth (20.8% vs 9.5%; P = .030) were the most important elements accounting for the difference. Furthermore, a trend toward more type I endoleaks during follow-up was observed (15.6% vs 7.4%; P = .063) and no difference in overall survival. The current study shows that patients with a familial form of AAA develop more aneurysm-related complications after EVAR, despite similar AAA morphology at baseline. These findings suggest that patients with fAAA form a specific subpopulation and create awareness for a possible increase in the risk of complications after EVAR.

KLF4 Regulates Abdominal Aortic Aneurysm Morphology and Deletion Attenuates Aneurysm Formation

KLF4 mediates inflammatory responses after vascular injury/disease; however, the role of KLF4 in abdominal aortic aneurysms (AAAs) remains unknown. The goals of the present study were to (1) determine the role of KLF4 in experimental AAA; and (2) determine the effect of KLF4 on smooth muscle (SM) cells in AAAs. KLF4 expression progressively increased at days 3, 7, and 14 after aortic elastase perfusion in C57BL/6 mice. Separately, loss of a KLF4 allele conferred AAA protection using ERTCre+ KLF4 flx/wt mice in the elastase AAA model. In a third set of experiments, SM-specific loss of 1 and 2 KLF4 alleles resulted in progressively greater protection using novel transgenic mice (MYHCre+ flx/flx, flx/wt, and wt/wt) in the elastase AAA model compared with control. Elastin degradation, MAC2, and cytokine production (MCP1, tumor necrosis factor-α, and interleukin-23) were significantly attenuated, whereas α-actin staining was increased in KLF4 knockout mice versus controls. Results were verified in global KLF4 and SM-specific knockout mice using an angiotensin II model of aneurysm formation. KLF4 inhibition with siRNA attenuated downregulation of SM gene expression in vitro, whereas in vivo studies demonstrated that KLF4 binds to promoters of SM genes by chromatin immunoprecipitation analysis. Finally, human aortic aneurysms demonstrated significantly higher KLF4 expression that was localized to SM cells. KLF4 plays a critical role in aortic aneurysm formation via effects on SM cells. These results suggest that KLF4 regulates SM cell phenotypic switching and could be a potential therapeutic target for AAA disease.

St George's Vascular Institute Protocol: An Accurate and Reproducible Methodology to Enable Comprehensive Characterization of Infrarenal Abdominal Aortic Aneurysm Morphology in Clinical and Research Applications

To define the reproducibility of a protocol for the analysis of infrarenal abdominal aortic aneurysm (AAA) morphology for clinical and research purposes. A protocol for the comprehensive assessment of preoperative AAA morphology based on formal systematic review and expert opinion featured 114 morphological parameters (maximum and minimum diameters, cross-sectional areas, vessel lengths, volumes, angulation, and calcification and tortuosity indices) in each of 3 regions: the neck, sac, and access vessels. To validate the protocol, 4 observers measured these variables on the preoperative computed tomographic angiograms from 50 patients (45 men; mean age 75 years, range 52-89) scheduled for endovascular aneurysm repair using software for 3-dimensional image reconstruction. One observer performed repeated measurements. The intra- and interobserver variabilities were calculated for all parameters; measurement time for all 114 features was recorded. Aortoiliac diameter, length, volume, area, and tortuosity index measurements showed good inter/intraobserver agreement. Aortic neck and aortoiliac angle measurements displayed high intra/interobserver repeatability coefficients (28%-43% and 29%-61%, respectively). Calcification measurements had the highest variability within and between observers: 39%-65% and 44%-96%, respectively. The measurement protocol was completed in a mean 105 minutes (range 55-420). Accurate 3-dimensional analysis of AAA morphology can be performed reliably within a reasonable time. Measurements that relied on consistent anatomical landmarks were most reproducible. Assessment of angulation and calcification required a number of subjective judgments, increasing the potential for variation. Automated methods are likely to be more suitable for certain measurements.

Murine ultrasound imaging for circumferential strain analyses in the angiotensin II abdominal aortic aneurysm model

The underlying causes of abdominal aortic aneurysms (AAAs) remain obscure, although research tools such as the angiotensin II (Ang II) apolipoprotein E-deficient (apoE(-/-)) mouse model have aided investigations. Longitudinal imaging and determination of biomechanical forces in this small-scale model have been difficult. We hypothesized that high-frequency ultrasound biomicroscopy combined with speckle-tracking analytical strategies can be used to define the role of circumferential mechanical strain in AAA formation in the Ang II/apoE(-/-) mouse model of AAAs. We simultaneously examined dietary perturbations that might impact the biomechanical properties of the aortic wall, hypothesizing that the generalized inflammatory phenotype associated with diet-induced obesity would be associated with accelerated loss of circumferential strain and aneurysmal aortic degeneration. Receiving either a 60 kcal% fat Western diet or standard 10 kcal% fat normal chow, Ang II-treated apoE(-/-) mice (n = 34) underwent sequential aortic duplex ultrasound scan imaging (Vevo 2100 System; VisualSonics, Toronto, Ontario, Canada) of their entire aorta. Circumferential strains were calculated using speckle-tracking algorithms and a custom MatLab analysis. Decreased strains in all aortic locations after just 3 days of Ang II treatment were observed, and this effect progressed during the 4-week observation period. Anatomic segments along the aorta impacted wall strain (baseline highest in ascending aorta; P < .05), whereas diet did not. At 2 and 4 weeks, there was the largest progressive decrease in strain in the paravisceral/supraceliac aorta (P < .05), which was the segment most likely to be involved in aneurysm formation in this model. In the Ang II/apoE(-/-) aneurysm model, the aorta significantly stiffens (with decreased strain) shortly after Ang II infusion, and this progressively continues through the next 4 weeks. High-fat feeding did not have an impact on wall strain. Delineation of biomechanical factors and AAA morphology via duplex scan and speckle-tracking algorithms in mouse models should accelerate insights into human AAAs.