Abdominal Aortic Aneurysm Volume Research Articles

Relative Thrombus Burden Ratio Reveals Overproportioned Intraluminal Thrombus Growth-Potential Implications for Abdominal Aortic Aneurysm.

Background: An intraluminal, non-occlusive thrombus (ILT) is a common feature in an abdominal aortic aneurysm (AAA). This study investigated the relative progression of ILT vs. AAA volume using a novel parameter, the so-called thrombus burden ratio (TBR), in non-treated AAAs. Parameters potentially associated with TBR progression were analyzed and TBR progression in large vs. small and fast- vs. slow-growing AAAs was assessed. Methods: This retrospective, single-center study analyzed sequential contrast-enhanced computed tomography angiography (CTA) scans between 2009 and 2018 from patients with an AAA before surgical treatment. Patients' medical data and CTA scans were analyzed at two given time points. The TBR was calculated as a ratio of ILT and AAA volume, and relative TBR progression was calculated by normalization for time between sequential CTA scans. Spearman's correlation was applied to identify morphologic parameters correlating with TBR progression, and multivariate linear regression analysis was used to evaluate the association of clinical and morphological parameters with TBR progression. Results: A total of 35 patients were included. The mean time between CT scans was 16 ± 15.9 months. AAA volume progression was 12 ± 3% and ILT volume progression was 36 ± 13%, resulting in a TBR progression of 11 ± 4%, suggesting overproportioned ILT growth. TBR progression was 0.8 ± 0.8% per month. Spearman's correlation verified ILT growth as the most relevant parameter contributing to TBR progression (R = 0.51). Relative TBR progression did not differ significantly in large vs. small and fast- vs. slow-growing AAAs. In the multivariate regression analysis, none of the studied factors were associated with TBR progression. Conclusion: TBR increases during AAA development, indicating an overproportioned ILT vs. AAA volume growth. The TBR may serve as a useful parameter, as it incorporates the ILT volume growth relative to the AAA volume, therefore combining two important parameters that are usually reported separately. Yet, the clinical relevance in helping to identify potential corresponding risk factors and the evaluation of patients at risk needs to be further validated in a larger study cohort.

Abdominal Aortic Aneurysm Response to Interleukin-10 Hydrogel-Based “Bio-Ink” Therapy in Rodent Models

Abdominal Aortic Aneurysms (AAA) are the pathological expansion of the aorta, which can rupture and cause significant mortality. Approximately 200,000 AAA cases occur annually in the US, with more than 15,000 cases resulting in death. Risk factors for AAA are similar to those of cardiovascular disease states, particularly cigarette smoking, and AAA patients are generally elderly, Caucasian males. Currently, no medical therapy exists for AAA outside of surgical intervention. We previously hypothesized that the early initiation and propagation of stages in AAA development are inflammatory driven. This process results in a weaker aortic wall, whichwe have evidenced through increased elastin breakdown products and inflammatory markers in AAA patients in comparison to matched controls. This project investigated the use of a novel anti-inflammatory hydrogel to ameliorate AAA progression.
 Our study uses a gelatin-based biodegradable bio-ink containing the anti-inflammatory cytokine interleukin-10 (IL-10), which was applied to the aorta with a novel hydrogel extruding “BIOPENCIL” device. We used a previously described rodent model consisting of intra-luminal injection of elastase in the infrarenal aorta combined with topical application of calcium chloride; alternatively, topical calcium chloride was used alone for AAA development. The BIOPENCIL was used to deliver the hydrogel containing IL-10 or control at the time of AAA creation. The animals were euthanized 14 or 21 days post-procedure and evaluated for AAA volume, surface area, and diameter alongside molecular analyses to evaluate for immunological changes between control and treatment groups. We predict that the rodent groups treated with IL-10 will not have AAA expansion, while the control group will see AAA expansion. This is based onlongitudinal data from weekly ultrasounds and will be confirmed with microCT.

The Role of Aortic Volume in the Natural History of Abdominal Aortic Aneurysms and Post-Endovascular Aortic Aneurysm Repair Surveillance.

There has been a debate about whether maximum diameter can be solely used to assess the natural history of abdominal aortic aneurysm. The aim of the present review is to collect all the available evidence on the role of abdominal aortic aneurysm (AAA) volume in the natural history of AAAs, including small untreated AAAs and AAAs treated by EVAR. The current literature appears to reinforce the role of volume as a supplementary measure for evaluating the natural history of AAA, in both intact AAAs and after EVAR. The clinical impact of AAA volume measurements remains unclear. Several studies show that volumetric analysis can assess changes in AAAs and predict successful endoluminal exclusion after EVAR more accurately than diameter. However, most studies lack strict standardized measurement criteria and well-defined outcome definitions. It remains unclear whether volumetry could replace diameter assessment in defining the risk of rupture of AAAs and identifying clinically relevant sac growth.

Abdominal aortic aneurysms volume growth patterns with three-dimensional ultrasound.

Three-dimensional ultrasound (3D-US) and computed tomography (CT) have proven abdominal aortic aneurysm (AAA) volume a more sensitive measure of growth than diameter. This proof-of-concept study aimed to investigate the clinical applicability of two-dimensional ultrasound and 3D-US for AAA diameter and volume growth pattern evaluation. AAA patients with at least three follow-ups within a minimum of 24 months were included prospectively and consecutively from the COpenhagen Aneurysms CoHort (COACH). Individual diameter and volume growth rates were categorized as rapid, slow, or no growth (>6.0, 3.8-6.0, and ≤3.7 mm/year for diameter. >17.4, 8.8-17.3, and ≤8.7 mL/year for volume). Similarly, diameter and volume growth patterns were categorized as as linear, exponential, staccato, and indeterminate growth, based from individual regressions. Thirty patients were included, of which 19 (63%) had no diameter growth, 10 (33%) had slow growth, and one (3%) had rapid growth. Regarding volume, 11 (37%) patients had no growth, 12 (40%) had slow growth, and seven (23%) had rapid growth. Growth patterns according to diameter showed that 18 (60%) patients had linear growth, none had staccato or exponential growth. Twelve (40%) were indeterminate. Volume growth patterns found 19 (63%) patients with linear growth, 3 (10%) with staccato, and none with exponential growth. Eight (27%) were indeterminate. Analysis of AAA volume growth patterns is a practical and safe modality that seems more sensitive at detecting growth patterns than AAA diameter. Volume also detects more AAA growth than diameter.

Comparing maximum diameter and volume when assessing the growth of small abdominal aortic aneurysms using longitudinal CTA data: cohort study.

Monitoring of abdominal aortic aneurysms (AAAs) is currently based on serial measurements of maximum aortic diameter. Additional assessment of aneurysm volume has previously been proposed to possibly improve growth prediction and treatment decisions. To evaluate the use of supplementing volume measurements, the authors aimed to characterise the growth distribution of AAA volume and to compare the growth rates of the maximum diameter and volume at the patient level. Maximum diameter and volume were monitored every 6 months in 84 patients with small AAAs, with a total of 331 computed tomographic angiographies (with initial maximum diameters of 30-68mm). A previously developed statistical growth model for AAAs was applied to assess the growth distribution of volume and to compare individual growth rates for volume and for maximum diameter. The median (25-75% quantile) expansion in volume was 13.4 (6.5-24.7) % per year. Cube root transformed volume and maximum diameter showed a closely linear association with a within-subject correlation of 0.77. At the surgery threshold maximum diameter of 55mm, the median (25-75% quantile) volume was 132 (103-167)ml. In 39% of subjects, growth rates for volume and maximum diameter were equivalent, in 33% growth was faster in volume and in 27% growth was faster in maximum diameter. At the population level, volume and maximum diameter show a substantial association such that the average volume is approximately proportional to the average maximum diameter raised to a power of three. At the individual level, however, in the majority of patient's AAAs grow at different pace in different dimensions. Hence, closer monitoring of aneurysms with sub-critical diameter but suspicious morphology may benefit from complementing maximum diameter by volume or related measurements.

Associations of Tissue and Soluble LOX-1 with Human Abdominal Aortic Aneurysm.

Background Indication for prophylactic surgical abdominal aortic aneurysm (AAA) repair depends on the maximal aortic diameter. The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major receptor for uptake of oxidized low-density lipoprotein cholesterol and is implicated in atherosclerosis. A soluble form of LOX-1 (sLOX-1) has been discussed as a novel biomarker in coronary artery disease and stroke. Herein, we assessed the regulation of aortic LOX-1 as well as the diagnostic and risk stratification potential of sLOX-1 in patients with AAA. Methods and Results Serum sLOX-1 was assessed in a case-control study in AAA (n=104) and peripheral artery disease (n=104). sLOX-1 was not statistically different between AAA and peripheral artery disease but was higher in AAA (β=1.28, P=0.04) after adjusting for age, atherosclerosis, type 2 diabetes, prescription of statins, β-blockers, ACE inhibitors, and therapeutic anticoagulation. sLOX-1 was not associated with the aortic diameter, AAA volume, or the thickness of the intraluminal thrombus. Aortic LOX-1 mRNA expression tended to be higher in AAA when compared with disease, and expression was positively associated with cleaved caspase-3, smooth muscle actin, collagen, and macrophage content. Conclusions In AAA, sLOX-1 was differently affected by age, cardiometabolic diseases, and corresponding medical therapies. Comparison with nonatherosclerotic disease would be beneficial to further elucidate the diagnostic potential of sLOX-1, although it was not useful for risk stratification. Aneurysmal LOX-1 mRNA expression was increased and positively associated with smooth muscle cells and collagen content, suggesting that LOX-1 is eventually not deleterious in human AAA and could counteract AAA rupture.

3D-Ultrasound Based Mechanical and Geometrical Analysis of Abdominal Aortic Aneurysms and Relationship to Growth.

The heterogeneity of progression of abdominal aortic aneurysms (AAAs) is not well understood. This study investigates which geometrical and mechanical factors, determined using time-resolved 3D ultrasound (3D + t US), correlate with increased growth of the aneurysm. The AAA diameter, volume, wall curvature, distensibility, and compliance in the maximal diameter region were determined automatically from 3D + t echograms of 167 patients. Due to limitations in the field-of-view and visibility of aortic pulsation, measurements of the volume, compliance of a 60mm long region and the distensibility were possible for 78, 67, and 122 patients, respectively. Validation of the geometrical parameters with CT showed high similarity, with a median similarity index of 0.92 and root-mean-square error (RMSE) of diameters of 3.5mm. Investigation of Spearman correlation between parameters showed that the elasticity of the aneurysms decreases slightly with diameter (p = 0.034) and decreases significantly with mean arterial pressure (p < 0.0001). The growth of a AAA is significantly related to its diameter, volume, compliance, and surface curvature (p < 0.002). Investigation of a linear growth model showed that compliance is the best predictor for upcoming AAA growth (RMSE 1.70mm/year). To conclude, mechanical and geometrical parameters of the maximally dilated region of AAAs can automatically and accurately be determined from 3D + t echograms. With this, a prediction can be made about the upcoming AAA growth. This is a step towards more patient-specific characterization of AAAs, leading to better predictability of the progression of the disease and, eventually, improved clinical decision making about the treatment of AAAs.

Circulating biomarkers of cardiovascular disease are related to aneurysm volume in abdominal aortic aneurysm.

Surveillance programs in abdominal aortic aneurysms (AAA) are mainly based on imaging and leave room for improvement to timely identify patients at risk for AAA growth. Many biomarkers are dysregulated in patients with AAA, which fuels interest in biomarkers as indicators of disease progression. We examined associations of 92 cardiovascular disease (CVD)-related circulating biomarkers with AAA and sac volume. In a cross-sectional analysis, we separately investigated (1) 110 watchful waiting (WW) patients (undergoing periodic surveillance imaging without planned intervention) and (2) 203 patients after endovascular aneurysm repair (EVAR). The Cardiovascular Panel III (Olink Proteomics AB, Sweden) was used to measure 92 CVD-related circulating biomarkers. We used cluster analyses to investigate protein-based subphenotypes, and linear regression to examine associations of biomarkers with AAA and sac volume on CT scans. Cluster analyses revealed two biomarker-based subgroups in both WW and EVAR patients, with higher levels of 76 and 74 proteins, respectively, in one subgroup versus the other. In WW patients, uPA showed a borderline significant association with AAA volume. Adjusting for clinical characteristics, there was a difference of -0.092 (-0.148, -0.036) loge mL in AAA volume per SD uPA. In EVAR patients, after multivariable adjustment, four biomarkers remained significantly associated with sac volume. The mean effects on sac volume per SD difference were: LDLR: -0.128 (-0.212, -0.044), TFPI: 0.139 (0.049, 0.229), TIMP4: 0.110 (0.023, 0.197), IGFBP-2: 0.103 (0.012, 0.194). LDLR, TFPI, TIMP4, and IGFBP-2 were independently associated with sac volume after EVAR. Subgroups of patients with high levels of the majority of CVD-related biomarkers emphasize the intertwined relationship between AAA and CVD.ClinicalTrials.gov Identifier: NCT03703947.

Factors associated with all-cause mortality following endovascular abdominal aortic aneurysm repair.

Background: Knowledge of factors that influence all-cause mortality after endovascular abdominal aortic aneurysm repair (EVAR) could improve therapeutic strategies post-EVAR and thus patient prognosis. Our study aimed to evaluate the association between sociodemographic information, comorbidities, laboratory parameters, treatment, selected anatomical and genetic factors and all-cause mortality post-EVAR. Patients and methods: We reviewed all patients who had undergone elective EVAR for non-ruptured abdominal aortic aneurysm (AAA) between January 2010 and December 2019. AAA size (maximum diameter and volume) was measured using CT-angiography. Sac expansion was defined as at least 5 mm increase, sac regression as at least 5 mm decrease in the sac diameter determined at 36±3 months post-EVAR in relation to pre-EVAR AAA diameter. Adjustments were performed for age, hypertension, diabetes mellitus, dyslipidaemia, sex, smoking, number of lumbar arteries, patency of inferior mesenteric artery and number of reinterventions post-EVAR. Results: One hundred and sixty-two patients (150 men, 12 women) with a mean age of 72.6±7.3 years were included in the analysis. Pre-EVAR AAA diameter (HR 1.07; 95% CI 1.03 - 1.12; p=0.001), pre-EVAR AAA volume (HR 1.01; 95% CI 1.002 - 1.011; p=0.008), post-EVAR sac diameter (HR 1.06; 95% CI 1.03 - 1.10; p=0.000), post-EVAR sac volume (HR 1.01; 95% CI 1.002 - 1.011; p=0.006) and anticoagulation therapy (HR 2.46; 95% CI 1.18 - 5.14; p=0.019) were associated with higher mortality in multivariate analysis. Sac regression (HR 0.42; 95% CI 0.22 - 0.82; p=0.011), and treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) (HR 0.71; 95% CI 0.36 - 0.97; p=0.047) were associated with lower mortality. Conclusions: Greater pre- and post-EVAR diameter and volume, failure of sac regression and anticoagulation were associated with higher mortality post-EVAR. Reduced mortality was observed in patients treated with ACE inhibitors or ARBs, and in patients with AAA sac regression.

The Impact Associated with Changing Practice Patterns for the Treatment of Abdominal Aortic Aneurysms in the United States

We have witnessed an evolution in the treatment of abdominal aortic aneurysm (AAA) from open to endovascular repair. The implications that these changes have had on outcomes, have not been thoroughly studied. We evaluated the trends in volume of open and endovascular AAA repairs done nationwide in a recent 20-year period, and the outcomes associated with each type of repair, to assess how outcomes may have changed over this period. Patients with AAA undergoing elective open and endovascular repair between 2000 and 2020 were identified using the TriNetX Analytics Network, a federated network of nationwide healthcare organizations that provides deidentified patient data. Patients undergoing first-time elective endovascular or open AAA repair (infrarenal and visceral) from 2001 to 2020 were separated, plotted over time, and propensity score matched. Primary outcome was mortality; secondary outcomes included myocardial infarction (MI), pneumonia and acute kidney injury (AKI). Over the 20-year period we identified 21,368 endovascular patients and 6473 open patients. The endovascular volume surpassed open volume between 2004 and 2005 and we saw a steady increase in endovascular repairs (Fig 1). From 2001 to 2010, mortality was 2.35% for open and 0.98% for endovascular (P < .001); MI was 1.40% for open and 0.90% for endovascular (P = .0004); pneumonia was 2.77% for open and 1.03% for endovascular (P < .001); and AKI was 1.85% for open and 0.91% for endovascular (P = .0014). From 2011 to 2020 mortality was 5.07% for open and 3.89% for endovascular (P = .09); MI was 2.48% for open and 2.39% for endovascular (P = .375); pneumonia was 4.21% for open and 3.10% for endovascular (P = .02); and AKI was 6.53% for open and 4.65% for endovascular (P = .07). When mortality was plotted over time for endovascular and open repairs they both increased (Fig 2). With respect to open repairs the mortality for infrarenal AAA increased from 2001 to 2010 by 2.07% and from 2011 to 2020 by 16.20% (P = .004); visceral AAA increased from 2001 to 2010 by 5.45% and from 2010 to 2020 by 15.73% (P = .016). Endovascular AAA repair has steadily increased over time, while open repair decreased and subsequently increased to a steady state over the recent 20-year period. It appears our mortality has increased for both endovascular and open repair types despite our increased exposure to endovascular cases in practice. Mortality for endovascular repair was significantly higher from 2000 to 2009, but not for 2010 to 2020. Mortality increased significantly from the first decade for both infrarenal and visceral aneurysms.

Abdominal aortic aneurysm volume and relative intraluminal thrombus volume might be auxiliary predictors of rupture-an observational cross-sectional study.

The study aimed to identify differences and compare anatomical and biomechanical features between elective and ruptured abdominal aortic aneurysms (AAAs). Data (clinical, anatomical, and biomechanical) of 98 patients with AAA, 75 (76.53%) asymptomatic (Group aAAA) and 23 (23.46%) ruptured AAA (Group rAAA), were prospectively collected and analyzed. Anatomical, morphological, and biomechanical imaging markers like peak wall stress (PWS) and rupture risk equivalent diameter (RRED), comorbid conditions, and demographics were compared between the groups. Biomechanical features were assessed by analysis of Digital Imaging and Communication in Medicine images by A4clinics (Vascops), and anatomical features were assessed by 3Surgery (Trimensio). Binary and multiple logistic regression analysis were used and adjusted for confounders. Accuracy was assessed using receiving operative characteristic (ROC) curve analysis. In a multivariable model, including gender and age as confounder variables, maximal aneurysm diameter [MAD, odds ratio (OR) = 1.063], relative intraluminal thrombus (rILT, OR = 1.039), and total aneurysm volume (TAV, OR = 1.006) continued to be significant predictors of AAA rupture with PWS (OR = 1.010) and RRED (OR = 1.031). Area under the ROC curve values and correct classification (cc) for the same parameters and the model that combines MAD, TAV, and rILT were measured: MAD (0.790, cc = 75%), PWS (0.713, cc = 73%), RRED (0.717, cc = 55%), TAV (0.756, cc = 79%), rILT (0.656, cc = 60%), and MAD + TAV + rILT (0.797, cc = 82%). Based on our results, in addition to MAD, other important predictors of rupture that might be used during aneurysm surveillance are TAV and rILT. Biomechanical parameters (PWS, RRED) as valuable predictors should be assessed in prospective clinical trials. Similar studies on AAA smaller than 55 mm in diameter, even difficult to organize, would be of even greater clinical value.

Regulation of CD163 Receptor in Patients with Abdominal Aortic Aneurysm and Associations with Antioxidant Enzymes HO-1 and NQO1.

Red blood cells are found within the abdominal aortic aneurysm (AAA), in the intraluminal thrombus (ILT), and in neovessels. Hemolysis promotes aortic degeneration, e.g., by heme-induced reactive oxygen species formation. To reduce its toxicity, hemoglobin is endocytosed by the CD163 receptor and heme is degraded by heme oxygenase-1 (HO-1). A soluble form (sCD163) is discussed as an inflammatory biomarker representing the activation of monocytes and macrophages. HO-1 and NAD(P)H quinone dehydrogenase 1 (NQO1) are antioxidant genes that are induced by the Nrf2 transcription factor, but their regulation in AAA is only poorly understood. The aim of the present study was to analyze linkages between CD163, Nrf2, HO-1, and NQO1 and to clarify if plasma sCD163 has diagnostic and risk stratification potential. Soluble CD163 was 1.3-fold (p = 0.015) higher in AAA compared to patients without arterial disease. The difference remained significant after adjusting for age and sex. sCD163 correlated with the thickness of the ILT (rs = 0.26; p = 0.02) but not with the AAA diameter or volume. A high aneurysmal CD163 mRNA was connected to increases in NQO1, HMOX1, and Nrf2 mRNA. Further studies are needed to analyze the modulation of the CD163/HO-1/NQO1 pathway with the overall goal of minimizing the detrimental effects of hemolysis.

Contrast-enhanced CT radiomics improves the prediction of abdominal aortic aneurysm progression.

To determine if three-dimensional (3D) radiomic features of contrast-enhanced CT (CECT) images improve prediction of rapid abdominal aortic aneurysm (AAA) growth. This longitudinal cohort study retrospectively analyzed 195 consecutive patients (mean age, 72.4years ± 9.1) with a baseline CECT and a subsequent CT or MR at least 6months later. 3D radiomic features were measured for 3 regions of the AAA, viz. the vessel lumen only; the intraluminal thrombus (ILT) and aortic wall only; and the entire AAA sac (lumen, ILT, and wall). Multiple machine learning (ML) models to predict rapid growth, defined as the upper tercile of observed growth (> 0.25cm/year), were developed using data from 60% of the patients. Diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve (AUC) in the remaining 40% of patients. The median AAA maximum diameter was 3.9cm (interquartile range [IQR], 3.3-4.4cm) at baseline and 4.4cm (IQR, 3.7-5.4cm) at the mean follow-up time of 3.2 ± 2.4years (range, 0.5-9years). A logistic regression model using 7 radiomic features of the ILT and wall had the highest AUC (0.83; 95% confidence interval [CI], 0.73-0.88) in the development cohort. In the independent test cohort, this model had a statistically significantly higher AUC than a model including maximum diameter, AAA volume, and relevant clinical factors (AUC = 0.78, 95% CI, 0.67-0.87 vs AUC = 0.69, 95% CI, 0.57-0.79; p = 0.04). A radiomics-based method focused on the ILT and wall improved prediction of rapid AAA growth from CECT imaging. • Radiomic analysis of 195 abdominal CECT revealed that an ML-based model that included textural features of intraluminal thrombus (if present) and aortic wall improved prediction of rapid AAA progression compared to maximum diameter. • Predictive accuracy was higher when radiomic features were obtained from the thrombus and wall as opposed to the entire AAA sac (including lumen), or the lumen alone. • Logistic regression of selected radiomic features yielded similar accuracy to predict rapid AAA progression as random forests or support vector machines.

One-year volume growth of abdominal aortic aneurysms measured by extended field-of-view ultrasound.

Measurement of volume has the potential to detect subtle growth not recognized in the current surveillance paradigm of abdominal aortic aneurysms (AAAs). Currently available three-dimensional ultrasound allows for estimation of AAA volume, but for most patients, the AAA extends beyond the ultrasound field-of-view and only allows visualization of a partial AAA volume. A new extended field-of-view three-dimensional ultrasound protocol (XFoV US) has been found to improve the proportion of patients with visualization of the full AAA volume. To investigate the applicability of the XFoV US protocol in estimating AAA volume growth in follow-up, 86 patients with AAAs were recruited from the surveillance program at a university hospital. All were imaged by XFoV US at baseline and at one-year follow-up. Assessment of full volume, based on visualization of the AAA neck and bifurcation at both baseline and one-year follow-up, was achieved in 67/86 (78%) of patients. One-year mean growth in maximum diameter was 2.8 mm (6%/year), in centerline length 2.9 mm (4%/year), and in volume 15.9 mL (19%/year). In 17/67 (25%) of patients, volume growth was detected in diameter-stable AAAs. Baseline XFoV US volume was associated with one-year AAA volume growth, while, conversely, maximum baseline diameter was not associated with one-year AAA diameter growth. This study concludes that the XFoV US protocol provides a safe and repeatable modality for assessing AAA volume growth, and that AAA volume is a promising predictive measure of AAA growth.

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

BackgroundSac 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. MethodsPatients 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. ResultsOf 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. ConclusionsThis 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.

Anticoagulants and reduced thrombus load in abdominal aortic aneurysms assessed with three-dimensional contrast-enhanced ultrasound examination.

The relationship between intraluminal thrombus (ILT) and abdominal aortic aneurysm (AAA) growth and rupture risk remains ambiguous. Studies have shown a limited effect of antiplatelet therapy on ILT size, whereas the impact of anticoagulant therapy on ILT is unresolved. This study aims to evaluate an association between antithrombotic therapy and ILT size assessed with three-dimensional contrast-enhanced ultrasound (3D-CEUS) examination in a cohort of patients with AAA. In a cross-sectional study, 309 patients with small AAAs were examined with 3D-CEUS. Patients were divided into three groups based on prescribed antithrombotic therapy: anticoagulant (n= 36), antiplatelet (n= 222), and no antithrombotic therapy (n= 51). Patient ILT size was calculated in volume and thickness and compared between the three groups. Patients on anticoagulants had a significantly lower estimated marginal mean ILT volume of 16mL (standard error [SE],±3.2) compared with 28mL (SE,±2.7) in the no antithrombotic group and 30mL (SE,±1.3) in the antiplatelet group when adjusting for AAA volume (P< .001) and comorbidities (P< .001). In addition, patients on anticoagulant therapy had significantly lower estimated marginal mean ILT thickness of 10mm (SE,±1.1) compared with 13mm (SE,±0.9) in the no antithrombotic group of and 13mm (SE,±0.4) in the antiplatelet group when adjusting for AAA diameter (P= .03) and comorbidities (P= .035). A 3D-CEUS examination is applicable for ILT assessment and demonstrates that patients with AAA on anticoagulant therapy have lower ILT thickness and volume than patients with AAA on antiplatelet therapy and those without antithrombotic therapy. Causality between anticoagulants and ILT size, and extrapolation to AAA growth and rupture risk, is unknown and merits further investigations, to further nuance US-based AAA surveillance strategy.

Rupture risk parameters upon biomechanical analysis independently change from vessel geometry during abdominal aortic aneurysm growth

ObjectiveThe indication for abdominal aortic aneurysm (AAA) repair is based on a diameter threshold. However, mechanical properties, such as peak wall stress (PWS) and peak wall rupture index (PWRI), influence the individual rupture risk. This study aims to correlate biomechanical and geometrical AAA characteristics during aneurysm growth applying a new linear transformation-based comparison of sequential imaging. MethodsPatients with AAA with two sequential computed tomography angiographies (CTA) were identified from a single-center aortic database. Patient characteristics included age, gender, and comorbidities. Semiautomated segmentation of CTAs was performed using Endosize (Therenva) for geometric variables (diameter, neck configuration, α/β angle, and vessel tortuosity) and for finite element method A4 Clinics Research Edition (Vascops) for additional variables (intraluminal thrombus [ILT]), vessel volume, PWS, PWRI). Maximum point coordinates from at least one CTA 6 to 24 months before their final were predicted for the final preoperative CTA using linear transformation along fix and validation points to estimate spatial motion. Pearson’s correlation and the t test were used for comparison. ResultsThirty-two eligible patients (median age, 70 years) were included. The annual AAA growth rate was 3.7 mm (interquartile range [IQR], 2.25-5.44; P < .001) between CTs. AAA (+17%; P < .001) and ILT (+43%; P < .001) volume, maximum ILT thickness (+35%; P < .001), β angle (+1.96°; P = .017) and iliac tortuosity (+0.009; P = .012) increased significantly. PWS (+12%; P = .0029) and PWRI (+16%; P < .001) differed significantly between both CTAs. Both mechanical parameters correlated most significantly with the AAA volume increase (r = 0.68 [P < .001] and r = 0.6 [P < .001]). Changes in PWS correlated best with the aneurysm neck configuration. The spatial motion of maximum ILT thickness was 14.4 mm (IQR, 7.3-37.2), for PWS 8.4 mm (IQR, 3.8-17.3), and 11.5 mm (IQR, 5.9-31.9) for PWRI. Here, no significant correlation with any of the aforementioned parameters, patient age, or time interval between CTs were observed. ConclusionsPWS correlates highly significant with vessel volume and aneurysm neck configuration. Spatial motion of maximum ILT thickness, PWS, and PWRI is detectable and predictable and might expose different aneurysm wall segments to maximum stress throughout aneurysm growth. Linear transformation could thus add to patient-specific rupture risk analysis. Clinical RelevanceAbdominal aortic aneurysm rupture risk assessment is a key feature in future individualized therapy approaches for patients, since more and more data are obtained concluding a heterogeneous disease entity that might not be addressed ideally looking only at diameter enlargement. The approach presented in this pilot study demonstrates the feasibility and importance of measuring peak wall stress and rupture risk indices based on predicted and actual position of maximum stress points including intraluminal thrombus.

Aneurysm Geometry Analyzed by the Novel Three-Dimensional Tomographic Ultrasound Relates to Abdominal Aortic Aneurysm Growth

Abdominal aortic aneurysms (AAAs) are increasingly screen-detected and many small aneurysms enter surveillance. Computed tomography identifies characteristics that can predict subsequent AAA growth but ionizing radiation and nephrotoxic contrast disadvantage its use in surveillance. We investigated whether duplex and 3-dimensional tomographic ultrasound identified features associated with AAA growth in patients on AAA surveillance. Duplex and three-dimensional tomographic ultrasound imaging was performed independently by 2 vascular scientists in 128 AAA surveillance patients who all had AAA growth measured over at least 2 years. Diameter, cross-sectional area, length, volume, wall thickness/volume, and intraluminal thrombus were measured. Pulsatility using maximum systolic and minimum diastolic diameters corrected for diameter and distensibility (consisting of strain and stiffness) were also calculated. AAA growth rate correlated with AAA diameter (r 0.43), volume (r 0.46), and cross-sectional area (r 0.42) (P < 0.01). Measuring wall thickness was inaccurate, but wall volume (corrected for AAA volume) inversely related to growth rate (r -0.43, P < 0.01). On a multivariate analysis, diameter and wall volume (r2adjusted 0.22, P < 0.01) improved prediction of growth rate compared with diameter alone (r2adjusted 0.18, P<0.01). Intraluminal thrombus volume, strain distensibility, and elastic distensibility were not significantly associated with AAA growth. AAA growth most strongly related to AAA volume and inversely to wall volume. AAA volume and wall volume may prove useful in the prediction of AAA growth rates.

Hemostatic Biomarkers and Volumetry Help to Identify High-Risk Abdominal Aortic Aneurysms.

Predicting the progression of small aneurysms is a main challenge in abdominal aortic aneurysm (AAA) management. The combination of circulating biomarkers and image techniques might provide an alternative for risk stratification. We evaluated the association of plasma TAT complexes (TAT) and D-dimer with AAA severity in 3 groups of patients: group 1, without AAA (n = 52), group 2, AAA 40–50 mm (n = 51) and group 3, AAA > 50 mm (n = 50). TAT (p < 0.001) and D-dimer (p < 0.001) were increased in patients with AAA (groups 2 and 3) vs. group 1. To assess the association between baseline TAT and D-dimer concentrations, and AAA growth, aortic diameter and volume (volumetry) were measured by computed tomography angiography (CTA) in group 2 at recruitment (baseline) and 1-year after inclusion. Baseline D-dimer and TAT levels were associated with AAA diameter and volume variations at 1-year independently of confounding factors (p ≤ 0.044). Additionally, surgery incidence, recorded during a 4-year follow-up in group 2, was associated with larger aneurysms, assessed by aortic diameter and volumetry (p ≤ 0.036), and with elevated TAT levels (sub-hazard ratio 1.3, p ≤ 0.029), while no association was found for D-dimer. The combination of hemostatic parameters and image techniques might provide valuable tools to evaluate AAA growth and worse evolution.

Allogeneic Mesenchymal Stromal Cells Increase Type 1 Regulatory T Cells and Decrease Aneurysm Volume in Patients With Small Abdominal Aortic Aneurysms

We have previously demonstrated that patients with abdominal aortic aneurysms (AAA) have a defect in IL-10 expression, type 1 regulatory T cell (Tr1) function and a robust Th17 response. In this phase I, double masked, placebo-controlled trial, we assess the efficacy of intravenous delivery of escalating doses of allogeneic mesenchymal stromal cells in modulating immune responses in patients with small AAA. Patients with AAA less than 5.0 cm in diameter were randomized 1:1:1 to receive intravenous administration of placebo (Plasmalyte A), 1 million mesenchymal stem cells (MSCs)/kg, or 3 million MSCs/kg. The primary end point were changes in Tr1 cells at day 14 after treatment as measured by fluorescent activated cell sorting. Secondary end points included changes in aneurysm inflammation at day 14 as measured by positron emission tomography and change in AAA volume at 1 year as measured by a computed tomography scan. Changes in plasma cytokines using enzyme linked immunoassay were measured at days 7, 14, and 28 after treatment. Treatment-related adverse outcomes and adverse cardiac events were recorded. A total of 28 patients (28 male; mean age 66 ± 4 years) with small AAA (mean diameter 3.9 ± 0.6 cm) were randomized to placebo (n = 12), 1 million MSCs/kg (n = 6), or 3 million MSCs/kg (n = 10). There was a significant increase in the percent of Tr1 cells at day 14 compared with placebo in the high dose group (73.2 ± 6.9% vs –5.5 ± 20.1%; P = .02), but not in the low-dose group. There was a decrease in Th17 cells at day 14 compared with placebo in the high and low dose groups (–11.1 ± 4.3% and –13.3 ± 4.6% vs 9.7 ± 5%, respectively; P < .05). Compared with placebo, there was a significant increase in IL-10 in the high- and low-dose groups (28.8 ± 3.2 pg/mL and 42.7 ± 4.5 pg/mL vs 11.9 ± 2.1 pg/mL; P = .034 and .023, respectively) at day 7. There was a decrease in aneurysm volume in the high-dose group compared with placebo at 1 year, but it was not quite significant (–7.3 ± 0.14 mm3vs 12.3 ± 2.6 mm3; P = .055) (Figure). There were no changes in aortic inflammation and no treatment-related adverse events. The ARREST study demonstrates that systemic administration of allogeneic MSCs is safe and may reduce AAA expansion. We plan a multicenter multidosing trial to further assess the potential of MSCs in preventing AAA expansion.