Small Abdominal Aortic Aneurysms Research Articles

Patient Perceptions of Surveillance of Small Abdominal Aortic Aneurysms in the Over 85s

Recently instigated local practice for patients with small abdominal aortic aneurysms (AAAs) involves contacting all patients, aged ≥85 years, to discuss with them the advantages and disadvantages of removal from surveillance. However, reasons why patients opt to remain on, or come off, surveillance, are currently unknown. The current study's objective is to explore patient perception of surveillance decision-making. A mixed-methods exploratory evaluation was undertaken using patient feedback obtained from a telephone survey. All patients aged ≥85 years, who had a consultation regarding ongoing surveillance of small AAAs (30-49mm), and consented, were contacted by researchers, who conducted semi-structured interviews concerning factors influencing decision-making. A total of 24 patients (20 male; mean age = 86.9 years) were interviewed; 16/24 (66%) had opted to remain on surveillance, with no age difference between those opting-in or out. Most felt surveillance was important (91%), and that it made them feel safer (73%). The majority (73%) thought they knew what happened when their AAA reached threshold (5.5cm), what happened when a threshold AAA is not fixed (64%), and how major AAA surgery is (59%). However, actual knowledge was poor: most (91%) correctly understood surgery was major; but 56% thought that threshold AAA meant certain death or rupture; and 38% thought immediate surgery was required. Thematic analysis expounded patients' beliefs regarding surveillance, which were summarised in three distinct sub-groups: reliance on professionals' opinions; needing peace of mind; and poor understanding. Whilst most patients find surveillance reassuring, patient knowledge of AAA management at threshold is poor, potentially impacting surveillance decision-making. Elderly patients, with small AAAs contemplating ongoing surveillance, need to be better informed about AAA management at threshold to support shared decision-making.

Multimodality magnetic resonance evaluating the effect of enhanced physical exercise on the growth rate, flow haemodynamics, aneurysm wall and ventricular-aortic coupling of patients with small abdominal aortic aneurysms (AAA MOVE trial): a study protocol for an open-label randomised controlled trial

IntroductionThe best lifestyle for small abdominal aortic aneurysms (sAAA) is essential for its conservative management. Physical exercise can improve the cardiopulmonary function of the patients, but it remains unclear which...

Biomechanical Characterization of Abdominal Aortic Aneurysm: The Rupture Mechanism

In this work, a four-week-old male C57Bl/6 mouse model of abdominal aortic aneurysm (AAA) was developed to examine the AAA rupture mechanism. Immunofluorescence staining was adopted for quantifying the degradation of elastin, and Picrosirius Red staining was adopted for evaluating the density of collagen. Atomic force microscopy with two probe tip sizes of 5 µm and 20 nm was adopted for mechanical characterization of the AAA. The microstructure changes and stiffness changes in both AAA samples and controlled samples were inspected. The degradation of elastin, wall thickening, formation of micro vessels, and increased density of collagen were observed in the AAA samples. The AAA samples also exhibited fragmented texture from AFM scanning. The histogram of stiffness measurements of the AAA samples with a 20 nm tip demonstrated two unique peak frequencies of stiffness intervals (0–10 kPa and 40–50 kPa). The stiffer regions were correlated with the increased density of collagen, as shown in the immunofluorescence images. The softer regions, combined with the fragmented texture, could be the key index contributing to the initiation and propagation of AAA rupture. Overall, the AAA group showed a higher stiffness than the control group (50.77 ± 62.4 kPa vs. 40.6 ± 51.86 kPa). The findings from this work may help in explaining ruptures in small AAA (<5.5 mm), which account for ten percent of all AAA ruptures. Additionally, the observations in this study may help develop early detection methods and innovative treatments for AAA.

Evaluation of Roxithromycin as a Treatment Option for Small Abdominal Aortic Aneurysms: An Integrated Study of Meta-analysis and Network Pharmacology.

Abdominal aortic aneurysm (AAA) is a segmental, progressive, and fatal vascular disorder, and the current strategy for small AAAs is close observation alone.The purpose of this study is to summarize the available evidence to assess the effects of antibiotics on small abdominal aortic aneurysms (AAA). We searched PubMed, EMBASE, Web of Science, and Scopus from inception to September 29, 2023, and included randomized controlled trials (RCTs) that evaluated the effects of antibiotics on small AAAs in humans. We first performed a meta-analysis to assess the effects of antibiotics on small AAAs. Afterward, network pharmacology analysis was applied to investigate the optimal drug generated from the meta-analysis results. We searched Pharmmapper and GeneCards to obtain the common potential targets of the selected drug and AAA-related targets. The protein-protein interaction network and functional enrichment analysis were performed by the STRING database, Cytoscape 3.7.2 software, and R, respectively. Docking studies were carried out for validation. We incorporated data from six RCTs involving a total of 997 patients. The results of this meta-analysis revealed that roxithromycin exhibited a modest yet statistically significant protective effect in terms of slowing down the AAA expansion rate. Furthermore, our subsequent bioinformatics analysis pinpointed MMP-2, MMP-9, ALB, MMP-3, and CCL-5 as potential therapeutic targets that could be explored for the treatment of AAA using roxithromycin. In conclusion, the study indicates roxithromycin is a promising drug for treating small AAAs and supports its underlying clinical use in small AAAs.

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.

Association of women-specific size threshold and mortality in elective abdominal aortic aneurysm repair.

It is unclear whether women derive mortality benefit from early repair of abdominal aortic aneurysms (AAA). The aim of this study was to compare short- and mid-term mortality for women treated at small versus large diameters. Women receiving elective repair of AAA at small (49-54 mm) and large (≥55 mm) diameters from 2008 to 2022 were extracted from the Swedish National Registry for Vascular Surgery (n = 1642 women). The effect of diameter on 90-day, 1- and 3-year mortality was studied in logistic regression and propensity score models. Age, co-morbidities, smoking and repair modality were considered as confounders. Men (n = 9047) were analysed in parallel. Some 1642 women were analysed, of whom 34% underwent repair at small diameters (versus 52% of men). Women with small (versus large) AAAs were younger (73 versus 75 years, P < 0.001), and 63% of women in both size groups had endovascular repairs (P = 0.120). Mortality was 3.5% (90 days), 7.1% (1 year) and 15.8% (3 years), with no differences between the size strata. There was no consistent association between AAA size and mortality in multivariable models. Sex differences in mortality were almost entirely due to mortality in younger-than-average women versus men (3-year mortality: small AAAs 11.1% versus 7.3%, P < 0.030, or large 14.4% versus 10.7%, P < 0.038). Mortality in women is high and unaffected by AAA size at repair. The optimal threshold for women remains undefined. The higher rupture risk in women should not automatically translate into a lower, women-specific threshold.

Next-Generation Sequencing of microRNAs in Small Abdominal Aortic Aneurysms: MiR-24 as a Biomarker

Small abdominal aortic aneurysms (AAAs) are asymptomatic but can potentially lead to rupture if left undetected. To date, there is a lack of simple nonradiologic routine tests available for diagnosing AAAs. MicroRNAs (miRNAs) have been proven to be good-quality biomarkers in several diseases, including AAA. An attempt to identify a panel of circulating miRNAs with differential expression in AAAs via next-generation sequencing (NGS) was performed in serum samples: small AAAs (n=3), large AAAs (n=3), and controls (n=3). For miR-24, validation with real-time polymerase chain reaction (PCR) was undertaken in a larger group (n=80). In the NGS study, 23 miRNAs were identified as differentially expressed (with statistical significance) in small AAAs in comparison with controls. Among them, miR-24 showed the largest upregulation with 23-fold change (log2FC 4.5, P=0.024). For large AAAs compared with controls, and small AAAs compared with large AAAs, a panel of 33 and 131 miRNAs showed statistically significant differential expression, respectively. Based on the results of the NGS stage, a literature search was performed, and information regarding AAA pathogenesis, coronary artery disease, and peripheral arterial disease was documented where applicable: miR-24, miR-103, miR-193a, miR-486, miR-582, and miR-3663. Of these 6 miRNAs, miR-24 was chosen for further validation with real-time PCR. Additionally, in the NGS study analysis, 17 miRNAs were common between the small-large AAAs, small AAAs-controls, and large AAAs-controls comparisons: miR-7846, miR-3195, miR-486-2, miR-3194, miR-5589, miR-1538, miR-3178, miR-4771-1, miR-5695, miR-6504, miR-1908, miR-6823, miR-3159, miR-23a, miR-7853, miR-496, and miR-193a. Interestingly, in the validation stage with real-time PCR, miR-24 was found downregulated in small and large AAAs compared with controls (fold-changes: 0.27, P=0.015 and 0.15, P=0.005, respectively). No correlation was found between average Ct values, aneurysm diameter, and patients' age. Our findings further highlight the importance of miR-24 as a potential biomarker as well as a therapeutic target for abdominal aneurysmal disease. Future research and validation of a panel of miRNAs for AAA would aid in diagnosis and discrimination between diseases with overlapping pathogeneses.

Assessing Efficacy of Afatinib toward Elastic Matrix Repair in Aortic Aneurysms.

Abdominal aortic aneurysm (AAA) is a critical, multifactorial cardiovascular disorder marked by localized dilatation of the abdominal aorta. A major challenge to countering the pathophysiology of AAAs lies in the naturally irreversible breakdown of elastic fibers in the aorta wall, which is linked to the poor elastogenicity of adult and diseased vascular smooth muscle cells (SMCs) and their impaired ability to assemble mature elastic fibers in a chronic proteolytic tissue milieu. We have previously shown that these are downstream effects of neutrophil elastase-induced activation of the epidermal growth factor receptor (EGFR) activity in aneurysmal SMCs. The novelty of this study lies in investigating the benefits of an EGFR inhibitor drug, afatinib (used to treat nonsmall cell lung cancer), for proelastogenic and antiproteolytic stimulation of aneurysmal SMCs. In in vitro cell cultures, we have shown that safe doses of 0.5 and 1 nM afatinib inhibit EGFR and p-extracellular signal-regulated kinases 1/2 protein expression by 50-70% and downstream elastolytic matrix metalloprotease 2 (MMP2) versus untreated control cultures. In addition, elastin production on a per cell basis was significantly upregulated by afatinib doses within the 0.1-1 nM dose range, which was further validated through transmission electron microscopy showing significantly increased presence of tropoelastin coacervates and maturing elastic fibers upon afatinib treatment at the above doses. Therefore, our studies for the first time demonstrate the therapeutic benefits of afatinib toward use for elastic matrix repair in small AAAs.

External Validation of a Prognostic Model for Survival of Patients With Abdominal Aortic Aneurysms Treated by Endovascular Aneurysm Repair

Current guidelines recommend diameter monitoring of small and asymptomatic abdominal aortic aneurysms (AAAs) due to the low risk of rupture. Elective AAA repair is recommended for diameters ≥ 5.5 cm in men and ≥ 5.0 cm in women. However, data supporting the efficacy of elective treatment for all patients above these thresholds are diverging. For a subgroup of patients, life expectancy might be very short, and elective AAA repair at the current threshold may not be justified. This study aimed to externally validate a predictive model for survival of patients with asymptomatic AAA treated with endovascular aneurysm repair (EVAR). This was a multicentre international retrospective observational cohort study. Data were collected from four European aortic centres treating patients between 2001 and 2021. The initial model included age, estimated glomerular filtration rate (eGFR), and chronic obstructive pulmonary disease (COPD) as independent predictors for survival. Model performance was measured by discrimination and calibration. The validation cohort included 1 500 patients with a median follow up of 65 months, during which 54.6% of the patients died. The external validation showed slightly decreased discrimination ability and signs of overfitting in model calibration. However, a high risk subgroup of patients with impaired survival rates was identified: octogenarians with eGFR < 60 OR COPD, septuagenarians with eGFR < 30, and septuagenarians with eGFR < 60 and COPD having survival rates of only 55.2% and 15.5% at five and 10 years, respectively. EVAR is a valuable treatment option for AAA, especially for patients unsuitable for open repair. Nonetheless, not all these patients will benefit from EVAR, and an individualised treatment recommendation should include considerations on life expectancy. This study provides a risk stratification to identify patients who may not benefit from EVAR under the present diameter threshold.

Systematic Review and Meta-Analysis of the Incidence of Rupture, Repair, and Death of Small and Large Abdominal Aortic Aneurysms under Surveillance.

The ultimate goal of treating patients with abdominal aortic aneurysms (AAAs) is to repair them when the risk of rupture exceeds the risk of repair. Small AAAs demonstrate a low rupture risk, and recently, large AAAs just above the threshold (5.5-6.0 cm) seem to be at low risk of rupture as well. The present review aims to investigate the outcomes of AAAs under surveillance through a comprehensive systematic review and meta-analysis. PubMed, Embase, and the Cochrane Central Register were searched (22 March 2022; PROSPERO; #CRD42022316094). The Cochrane and PRISMA statements were respected. Blinded systematic screening of the literature, data extraction, and quality assessment were performed by two authors. Conflicts were resolved by a third author. The meta-analysis of prevalence provided estimated proportions, 95% confidence intervals, and measures of heterogeneity (I2). Based on I2, the heterogeneity might be negligible (0-40%), moderate (30-60%), substantial (50-90%), and considerable (75-100%). The primary outcome was the incidence of AAA rupture. Secondary outcomes included the rate of small AAAs reaching the threshold for repair, aortic-related mortality, and all-cause mortality. Fourteen publications (25,040 patients) were included in the analysis. The outcome rates of the small AAA group (<55 mm) were 0.3% (95% CI 0.0-1.0; I2 = 76.4%) of rupture, 0.6% (95% CI 0.0-1.9; I2 = 87.2%) of aortic-related mortality, and 9.6% (95% CI 2.2-21.1; I2 = 99.0%) of all-cause mortality. During surveillance, 21.4% (95% CI 9.0-37.2; I2 = 99.0%) of the initially small AAAs reached the threshold for repair. The outcome rates of the large AAA group (>55 mm) were 25.7% (95% CI 18.0-34.3; I2 = 72.0%) of rupture, 22.1% (95% CI 16.5-28.3; I2 = 25.0%) of aortic-related mortality, and 61.8% (95% CI 47.0-75.6; I2 = 89.1%) of all-cause mortality. The sensitivity analysis demonstrated a higher rupture rate in studies including <662 subjects, patients with a mean age > 72 years, >17% of female patients, and >44% of current smokers. The rarity of rupture and aortic-related mortality in small AAAs supports the current conservative management of small AAAs. Surveillance seems indicated, as one-fifth reached the threshold for repair. Large aneurysms had a high incidence of rupture and aortic-related mortality. However, these data seem biased by the sparse and heterogeneous literature overrepresented by patients unfit for surgery. Specific rupture risk stratified by age, gender, and fit-for-surgery patients with large AAAs needs to be further investigated.

JNK2 silencing lipid nanoparticles for elastic matrix repair.

The over-expression of c-Jun N-terminal kinase (JNK2), a stress activated mitogen kinase, in the aortic wall plays a critical role in the formation and progression of abdominal aortic aneurysm (AAA). This triggers chronic downstream upregulation of elastolytic matrix metalloproteinases (MMPs), MMPs2 and 9 to cause progressive proteolytic breakdown of the wall elastic matrix. We have previously shown that siNRA knockdown of JNK2 gene expression in an AAA culture model stimulates downstream elastin gene expression, elastic fiber formation, crosslinking and reduces elastolytic MMPs2 and 9. Since naked siRNA poorly routes to intracellular targets, has poor stability in blood, and could be potentially toxic and immunogenic, this project is aimed to develop PEGylated lipid nanoparticles (LNPs) for delivery of JNK siRNA and to generate evidence of successful JNK2 knockdown and downstream attenuation of MMP2 gene and protein expressions. LNPs were formulated using thin-film hydration technique and had the size of 100-200 nm with zeta-potential ranging between 30 and 40 mV. JNK siRNA loaded PEGylated LNPs successfully knocked down JNK2 in cytokine-activated rat aneurysmal smooth muscle (EaRASMC) cultures. This resulted in a downstream decrease in MMP2 gene and protein expression and an upward trend in expression of genes for proteins critical for elastic fiber assembly such as elastin (ELN) and lysyl oxidase (LOX). Our result indicates cationic LNPs to be potential carriers for JNK siRNA delivery improving potency for elastin homeostasis required for AAA repair which could possibly provide benefits in preventing the progression of small AAAs.

Intermediate pressure-normalized principal wall strain values are associated with increased abdominal aortic aneurysmal growth rates.

Current abdominal aortic aneurysm (AAA) assessment relies on analysis of AAA diameter and growth rate. However, evidence demonstrates that AAA pathology varies among patients and morphometric analysis alone is insufficient to precisely predict individual rupture risk. Biomechanical parameters, such as pressure-normalized AAA principal wall strain (/PP, %/mmHg), can provide useful information for AAA assessment. Therefore, this study utilized a previously validated ultrasound elastography (USE) technique to correlate /PP with the current AAA assessment methods of maximal diameter and growth rate. Our USE algorithm utilizes a finite element mesh, overlaid a 2D cross-sectional view of the user-defined AAA wall, at the location of maximum diameter, to track two-dimensional, frame-to-frame displacements over a full cardiac cycle, using a custom image registration algorithm to produce /PP. This metric was compared between patients with healthy aortas and AAAs (≥3 cm) and compared between small and large AAAs (≥5 cm). AAAs were then separated into terciles based on /PP values to further assess differences in our metric across maximal diameter and prospective growth rate. Non-parametric tests of hypotheses were used to assess statistical significance as appropriate. USE analysis was conducted on 129 patients, 16 healthy aortas and 113 AAAs, of which 86 were classified as small AAAs and 27 as large. Non-aneurysmal aortas showed higher /PP compared to AAAs (0.044 ± 0.015 vs. 0.034 ± 0.017%/mmHg, p = 0.01) indicating AAA walls to be stiffer. Small and large AAAs showed no difference in /PP. When divided into terciles based on /PP cutoffs of 0.0251 and 0.038%/mmHg, there was no difference in AAA diameter. There was a statistically significant difference in prospective growth rate between the intermediate tercile and the outer two terciles (1.46 ± 2.48 vs. 3.59 ± 3.83 vs. 1.78 ± 1.64 mm/yr, p = 0.014). There was no correlation between AAA diameter and /PP, indicating biomechanical markers of AAA pathology are likely independent of diameter. AAAs in the intermediate tercile of /PP values were found to have nearly double the growth rates than the highest or lowest tercile, indicating an intermediate range of /PP values for which patients are at risk for increased AAA expansion, likely necessitating more frequent imaging follow-up.

Characterization of small abdominal aortic aneurysms' growth status using spatial pattern analysis of aneurismal hemodynamics

Aneurysm hemodynamics is known for its crucial role in the natural history of abdominal aortic aneurysms (AAA). However, there is a lack of well-developed quantitative assessments for disturbed aneurysmal flow. Therefore, we aimed to develop innovative metrics for quantifying disturbed aneurysm hemodynamics and evaluate their effectiveness in predicting the growth status of AAAs, specifically distinguishing between fast-growing and slowly-growing aneurysms. The growth status of aneurysms was classified as fast (≥ 5 mm/year) or slow (< 5 mm/year) based on serial imaging over time. We conducted computational fluid dynamics (CFD) simulations on 70 patients with computed tomography (CT) angiography findings. By converting hemodynamics data (wall shear stress and velocity) located on unstructured meshes into image-like data, we enabled spatial pattern analysis using Radiomics methods, referred to as "Hemodynamics-informatics" (i.e., using informatics techniques to analyze hemodynamic data). Our best model achieved an AUROC of 0.93 and an accuracy of 87.83%, correctly identifying 82.00% of fast-growing and 90.75% of slowly-growing AAAs. Compared with six classification methods, the models incorporating hemodynamics-informatics exhibited an average improvement of 8.40% in AUROC and 7.95% in total accuracy. These preliminary results indicate that hemodynamics-informatics correlates with AAAs' growth status and aids in assessing their progression.

Early Relative Growth Rate of Abdominal Aortic Aneurysms and Future Risk of Rupture or Repair

This study aimed to test whether the relative growth rate of subthreshold abdominal aortic aneurysms (AAAs) in the first 24 months of surveillance predicts the risk of future rupture or repair. This was a single centre retrospective observational analysis of all small (< 45 mm diameter) and medium (45 - 54 mm in men, 45 - 50 mm in women) AAAs entered into ultrasound surveillance between January 2002 and December 2019, which received ≥ 24 months of surveillance. Relative growth rates were calculated from measurements taken in the first 24 months of surveillance. The Kaplan-Meier method was used to estimate intervention and rupture free proportions five years following diagnosis for AAAs growing by < 5% and by ≥ 5% in the first 24 months of surveillance. Multivariable Cox regression analysis was used to further analyse this relationship by adjusting for factors found to be significantly associated with outcome in univariable analysis. A total of 556 patients with AAAs (409 men, 147 women) were followed for ≥ 24 months. This included 431 small AAAs. Of these, 109 (25.3%) grew by < 5% in the first 24 months of surveillance and had a cumulative event free proportion of 0.98 ± 0.05 at five years compared with 0.78 ± 0.05 for the ≥ 5% growth group (p < .001). Of 125 medium AAAs, 26 (20.8%) grew by < 5% in the first 24 months of surveillance and had a cumulative event free proportion of 0.73 ± 0.11 at five years compared with 0.29 ± 0.13 for the ≥ 5% growth group (p= .024). Baseline diameter and early relative growth rate were strongly and independently predictive of future intervention or rupture with hazard ratios of 9.16 (95% CI 5.98 - 14.03, p < .001) and 4.46 (95% CI 2.45 - 8.14, p < .001), respectively. The results suggest that slow expansion of small (< 45 mm) AAAs observed over an isolated 24 month period is indicative of a very low risk of rupture or repair in the medium term. Isolated growth rates may be a useful tool with which to triage low risk AAAs and prevent unnecessary surveillance.

Targeted PERK inhibition with biomimetic nanoclusters confers preventative and interventional benefits to elastase-induced abdominal aortic aneurysms.

Abdominal aortic aneurysm (AAA) is a progressive aortic dilatation, causing ∼80% mortality upon rupture. Currently, there is no approved drug therapy for AAA. Surgical repairs are invasive and risky and thus not recommended to patients with small AAAs which, however, account for ∼90% of the newly diagnosed cases. It is therefore a compelling unmet clinical need to discover effective non-invasive strategies to prevent or slow down AAA progression. We contend that the first AAA drug therapy will only arise through discoveries of both effective drug targets and innovative delivery methods. There is substantial evidence that degenerative smooth muscle cells (SMCs) orchestrate AAA pathogenesis and progression. In this study, we made an exciting finding that PERK, the endoplasmic reticulum (ER) stress Protein Kinase R-like ER Kinase, is a potent driver of SMC degeneration and hence a potential therapeutic target. Indeed, local knockdown of PERK in elastase-challenged aorta significantly attenuated AAA lesions in vivo. In parallel, we also conceived a biomimetic nanocluster (NC) design uniquely tailored to AAA-targeting drug delivery. This NC demonstrated excellent AAA homing via a platelet-derived biomembrane coating; and when loaded with a selective PERK inhibitor (PERKi, GSK2656157), the NC therapy conferred remarkable benefits in both preventing aneurysm development and halting the progression of pre-existing aneurysmal lesions in two distinct rodent models of AAA. In summary, our current study not only establishes a new intervention target for mitigating SMC degeneration and aneurysmal pathogenesis, but also provides a powerful tool to facilitate the development of effective drug therapy of AAA.

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.

Pathogenesis and management of abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) causes ∼170 000 deaths annually worldwide. Most guidelines recommend asymptomatic small AAAs (30 to <50 mm in women; 30 to <55 mm in men) are monitored by imaging and large asymptomatic, symptomatic, and ruptured AAAs are considered for surgical repair. Advances in AAA repair techniques have occurred, but a remaining priority is therapies to limit AAA growth and rupture. This review outlines research on AAA pathogenesis and therapies to limit AAA growth. Genome-wide association studies have identified novel drug targets, e.g. interleukin-6 blockade. Mendelian randomization analyses suggest that treatments to reduce low-density lipoprotein cholesterol such as proprotein convertase subtilisin/kexin type 9 inhibitors and smoking reduction or cessation are also treatment targets. Thirteen placebo-controlled randomized trials have tested whether a range of antibiotics, blood pressure-lowering drugs, a mast cell stabilizer, an anti-platelet drug, or fenofibrate slow AAA growth. None of these trials have shown convincing evidence of drug efficacy and have been limited by small sample sizes, limited drug adherence, poor participant retention, and over-optimistic AAA growth reduction targets. Data from some large observational cohorts suggest that blood pressure reduction, particularly by angiotensin-converting enzyme inhibitors, could limit aneurysm rupture, but this has not been evaluated in randomized trials. Some observational studies suggest metformin may limit AAA growth, and this is currently being tested in randomized trials. In conclusion, no drug therapy has been shown to convincingly limit AAA growth in randomized controlled trials. Further large prospective studies on other targets are needed.

Characteristics and 1-year outcomes of patients with rupture of small abdominal aortic aneurysms

Objectives: Ruptured abdominal aortic aneurysms (rAAA) are associated typically with a large sac diameter; however, some patients experience rupture before reaching operative thresholds for elective repair. We aim to investigate the characteristics and outcomes of patients who experience small rAAA.

Rare Rupture of Small 4.3cm Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) is a common medical condition with the feared, and often fatal, complication of rupture. The risk of rupture has been well documented to correlate with aneurysm size. It is exceedingly rare for an AAA less than 5cm to rupture. This case report demonstrates an asymptomatic 4.3cm AAA that ruptured while admitted to the hospital with COVID-19 pneumonia. The patient was successfully managed with an endovascular aortoiliac stent graft. Although rare, in patients with small AAA, rupture must remain in the differential diagnosis in the setting of acute onset abdominal or back pain. Furthermore, when quickly recognized, these patients can be safely managed with an endovascular approach.

Intermediate Pressure-Normalized Strain Values Are Associated With Increased Abdominal Aortic Aneurysmal Growth Rates

Current abdominal aortic aneurysm (AAA) assessment methods rely on simple morphometric analysis of the AAA diameter and growth rate. However, evidence has shown that AAA pathology varies among patients, and morphometric analysis alone is insufficient to predict individual risk of growth. Biomechanical parameters, such as pressure-normalized aortic wall strain (εp+/PP), can provide a surrogate to vessel wall stiffness. We aimed to use our novel ultrasound elastography (USE) technique to measure ερ+/PP and correlate ερ+/PP with maximal AAA diameter and growth rate in the largest clinical trial to date. Our USE algorithm uses a finite element mesh overlayed on a 2D axial view of the user-defined AAA wall at the point of maximum diameter to track frame-to-frame displacements over a full cardiac cycle to measure ερ+/PP. ερ+/PP and growth rate were assessed between small and large AAAs based on a diameter of ≥5 cm. Patients with AAA were then separated into terciles based on ερ+/PP values of 0.0251 and 0.038 to assess differences in the AAA diameter and growth rate. Mann-Whitney U and Kruskal-Wallis tests were used to assess differences as appropriate. USE analysis was conducted on 127 patients, 16 normal aortas and 111 AAAs. A total of 79 patients had at least one follow-up clinical scan used to calculate growth rate. Of the 111 aortas, 85 were classified as small and 26 as large. AAAs showed lower ερ+/PP (stiffer) compared with nonaneurysmal aortas (0.034 ± 0.017 vs 0.044 ± 0.015 %/kPa; P = .006). There was no difference in ερ+/PP or growth rate between small and large AAAs. When divided into terciles based on ερ+/PP, there was no difference in the AAA diameter. There was a statistically significant difference in growth rate between the intermediate tercile and the outer terciles (1.46 ± 2.48 vs 3.59 ± 3.83 vs 1.78 ± 1.64 mm/y; P = .014) (Fig). Our validated USE algorithm shows that AAAs are stiffer than nonaneurysmal aortas, similar to previous reports. There was no correlation between AAA diameter and ερ+/PP, indicating that AAA stiffness is independent of diameter, and diameter thresholds alone may not accurately assess future risk of growth. AAAs in the intermediate tercile of ερ+/PP values were found to have greater growth rates than the outer tercile, indicating that an intermediate range of ερ+/PP values, regardless of diameter, place patients at increased risk for AAA growth. These findings also suggest that AAA growth may be related to a failure of collagen remodeling and may be the underlying event that leads to AAA rupture.