Abdominal Aortic Aneurysm Rupture Research Articles

Construction of ferroptosis-related prediction model for pathogenesis, diagnosis and treatment of ruptured abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a dangerous cardiovascular disease, which often brings great psychological burden and economic pressure to patients. If AAA rupture occurs, it is a serious threat to patients' lives. Therefore, it is of clinical value to actively explore the pathogenesis of ruptured AAA and prevent its occurrence. Ferroptosis is a new type of cell death dependent on lipid peroxidation, which plays an important role in many cardiovascular diseases. In this study, we used online data and analysis of ferroptosis-related genes to uncover the formation of ruptured AAA and potential therapeutic targets. We obtained ferroptosis-related differentially expressed genes (Fe-DEGs) from GSE98278 dataset and 259 known ferroptosis-related genes from FerrDb website. Enrichment analysis of differentially expressed genes (DEGs) was performed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG). Receiver Operating characteristic (ROC) curve was employed to evaluate the diagnostic abilities of Fe-DEGs. Transcription factors and miRNAs of Fe-DEGs were identified through PASTAA and miRDB, miRWalk, TargetScan respectively. Single-sample gene set enrichment analysis (ssGSEA) was used to observe immune infiltration between the stable group and the rupture group. DGIdb database was performed to find potential targeted drugs of DEGs. GO and KEGG enrichment analysis found that DEGs mainly enriched in "cellular divalent inorganic cation homeostasis," "cellular zinc ion homeostasis," "divalent inorganic cation homeostasis," "Mineral absorption," "Cytokine - cytokine receptor interaction," "Coronavirus disease - COVID-19." Two up-regulated Fe-DEGs MT1G and DDIT4 were found to further analysis. Both single and combined applications of MT1G and DDIT4 showed good diagnostic efficacy (AUC = 0.8254, 0.8548, 0.8577, respectively). Transcription factors STAT1 and PU1 of MT1G and ARNT and MAX of DDIT4 were identified. Meanwhile, has_miR-548p-MT1G pairs, has_miR-53-3p/has_miR-181b-5p/ has_miR-664a-3p-DDIT4 pairs were found. B cells, NK cells, Th2 cells were high expression in the rupture group compared with the stable group, while DCs, Th1 cells were low expression in the rupture group. Targeted drugs against immunity, GEMCITABINE and INDOMETHACIN were discovered. We preliminarily explored the clinical significance of Fe-DEGs MT1G and DDIT4 in the diagnosis of ruptured AAA, and proposed possible upstream regulatory transcription factors and miRNAs. In addition, we also analyzed the immune infiltration of stable and rupture groups, and found possible targeted drugs for immunotherapy.

Roles and Mechanisms of miRNAs in Abdominal Aortic Aneurysm: Signaling Pathways and Clinical Insights.

Abdominal aortic aneurysm refers to a serious medical condition that can cause the irreversible expansion of the abdominal aorta, which can lead to ruptures that are associated with up to 80% mortality. Currently, surgical and interventional procedures are the only treatment options available for treating abdominal aortic aneurysm patients. In this review, we focus on the upstream and downstream molecules of the microRNA-related signaling pathways and discuss the roles, mechanisms, and targets of microRNAs in abdominal aortic aneurysm modulation to provide novel insights for precise and targeted drug therapy for the vast number of abdominal aortic aneurysm patients. Recent studies have highlighted that microRNAs, which are emerging as novel regulators of gene expression, are involved in the biological activities of regulating abdominal aortic aneurysms. Accumulating studies suggested that microRNAs modulate abdominal aortic aneurysm development through various signaling pathways that are yet to be comprehensively summarized. A total of six signaling pathways (NF-κB signaling pathway, PI3K/AKT signaling pathway, MAPK signaling pathway, TGF-β signaling pathway, Wnt signaling pathway, and P53/P21 signaling pathway), and a total of 19 miRNAs are intimately associated with the biological properties of abdominal aortic aneurysm through targeting various essential molecules. MicroRNAs modulate the formation, progression, and rupture of abdominal aortic aneurysm by regulating smooth muscle cell proliferation and phenotype change, vascular inflammation and endothelium function, and extracellular matrix remodeling. Because of the broad crosstalk among signaling pathways, a comprehensive analysis of miRNA-mediated signaling pathways is necessary to construct a well-rounded upstream and downstream regulatory network for future basic and clinical research of AAA therapy.

Effect of EVAR on International Ruptured AAA Mortality-Sex and Geographic Disparities.

Background: We sought to investigate the differential impact of EVAR (endovascular aneurysm repair) vis-à-vis OSR (open surgical repair) on ruptured AAA (abdominal aortic aneurysm) mortality by sex and geographically. Methods: We performed a retrospective study of administrative data on EVAR from state statistical agencies, vascular registries, and academic publications, as well as ruptured AAA mortality rates from the World Health Organization for 14 14 states across Australasia, East Asia, Europe, and North America. Results: Between 2011-2016, the proportion of treatment of ruptured AAAs by EVAR increased from 26.1 to 43.8 percent among females, and from 25.7 to 41.2 percent among males, and age-adjusted ruptured AAA mortality rates fell from 12.62 to 9.50 per million among females, and from 34.14 to 26.54 per million among males. The association of EVAR with reduced mortality was more than three times larger (2.2 vis-à-vis 0.6 percent of prevalence per 10 percentage point increase in EVAR) among females than males. The association of EVAR with reduced mortality was substantially larger (1.7 vis-à-vis 1.1 percent of prevalence per 10 percentage point increase in EVAR) among East Asian states than European+ states. Conclusions: The increasing adoption of EVAR coincided with a decrease in ruptured AAA mortality. The relationship between EVAR and mortality was more pronounced among females than males, and in East Asian than European+ states. Sex and ethnic heterogeneity should be further investigated.

Identification and Evaluation of Blood-Based Biomarkers for Abdominal Aortic Aneurysm.

Blood-based biomarkers for abdominal aortic aneurysm (AAA) have been studied individually; however, we considered a panel of proteins to investigate AAA prognosis and its potential to improve predictive accuracy. Using a prospectively recruited cohort of patients with/without AAA (n = 452), we conducted a prognostic study to develop a model that accurately predicts AAA outcomes using clinical features and circulating biomarker levels. Serum concentrations of 9 biomarkers were measured at baseline, and the cohort was followed for 2 years. The primary outcome was major adverse aortic event (MAAE; composite of rapid AAA expansion [>0.5 cm/6 months or >1 cm/12 months], AAA intervention, or AAA rupture). Using 10-fold cross-validation, we trained a random forest model to predict 2 year MAAE using (1) clinical characteristics, (2) biomarkers, and (3) clinical characteristics and biomarkers. Two-year MAAE occurred in 114 (25%) patients. Two proteins were significantly elevated in patients with AAA compared with those without AAA (angiopoietin-2 and aggrecan), composing the protein panel. For predicting 2 year MAAE, our random forest model achieved area under the receiver operating characteristic curve (AUROC) 0.74 using clinical features alone, and the addition of the 2-protein panel improved performance to AUROC 0.86. Using a combination of clinical/biomarker data, we developed a model that accurately predicts 2 year MAAE.

The role of diabetes on the development of abdominal aortic aneurysms (AAA)

An abdominal aortic aneurysm (AAA) is a pathological local dilatation of the abdominal aorta that may develop from a variety of causes. With a 80% mortality rate, it is mainly linked to male gender, age above 65 years, smoking, and a family history of AAA. Ultrasonography is an effective method for screening males who are 65 or older for AAA. Endovascular aneurysm repair (EVAR) procedure reduces 30-day operative mortality and hospital stay, becoming a global standard. Both open and endovascular surgery aim to cut off the aneurysm's circulation, preventing it from rupturing. Diabetes mellitus (DM) may provide protection against regrowth and the need for additional intervention after endovascular AAA repair, thereby limiting the enlargement and rupture of AAAs. Hyperglycemia thickens the aortic walls and reduces wall stress in diabetic patients' abdominal aortas. It stabilizes collagen structure and promotes the synthesis of collagen type IV. Anti-diabetic drugs like metformin, thiazolidinedione, and dipeptidyl peptidase 4 inhibitors (DPP-4i) have been shown in both animal and human studies to protect against aortic aneurysms. In a dose-response pattern, these antidiabetic drugs may lower the prevalence, incidence, and enlargement rate of AAA.

A Core Outcome Set for Intact Abdominal Aortic Aneurysm Repair

Technology and advances in clinical care have changed the management of abdominal aortic aneurysms (AAAs) but the clinical effectiveness of continuing advances needs to be assessed. To facilitate rapid synthesis of new evidence and improve stakeholder representation, including patients, the concept of core outcome sets has been developed. Core outcome sets, reflecting the needs of all stakeholders, have been established across several surgical specialties. This study aimed to develop an international core outcome set for intact AAA repair. Following COMET methodology, potential outcomes were identified from a systematic review of published outcomes and focus groups involving patients, carers, and nurses. A 38 question Delphi consensus survey in lay language was developed (with translation to local languages); this included 35 themes identified from the findings of the systematic review and three themes from the focus groups. All three of the themes identified by the focus groups (cognitive, physical, and social functioning) can be evaluated from quality of life instruments, with overall quality of life being identified from the systematic review. The survey was completed by patients, carers or family members, vascular nurses, vascular surgeons, trainees, interventional radiologists, anaesthetists, and industry partners from six European countries. After two rounds of the survey, the top outcomes were discussed at a face to face multistakeholder consensus meeting. The 38 item questionnaire was amended after piloting among all stakeholder groups. After the first round of the Delphi survey (98 respondents), 15 questions were eliminated and 11 further questions were eliminated after round two (90 respondents). This left two outcome questions for discussion at the consensus meeting, where the top six outcomes were unanimously endorsed: mortality at 30 days (or in hospital if longer), secondary AAA rupture, overall quality of life and retention of cognitive functioning after recovery, 5 year survival, and continued sac growth. Six core outcomes are recommended for use as a minimum framework in all future studies and registries of intact open and endovascular AAA repair. Further work to select instruments for quality of life and define instruments for cognitive functioning is needed.

Anesthetic Management for Abdominal Aortic Aneurysm Rupture

Background: Aortic aneurysm is the thirteenth leading cause of death in the united states. Around 15.000 people died each year because of aortic aneurysm rupture. The mortality rate for this case are still high at around 90%. Patient diagnosed with acute aortic rupture will need an urgent surgery.Case: A 36-year-old man came with complaints of pain in the waist to back area since 1 week before entering the hospital and worsening 2 days before entering the hospital. Pain is felt intermittent. The pain is sharp and severe when the patient strains. On physical examination found high blood pressure (160/104 mmHg), chest X-ray showed widening of the mediastinum suspected descending aortic aneurysm, CT angiography showed a fusiform type descending aortic aneurysm pars thoracoles, ruptured abdominal aortic aneurysm of juxtarenal fusiform type to the terminal abdominal aorta and hemoperitoneum. The patient underwent repair of an abdominal aortic aneurysm under general anesthesia. After surgery the patient was admitted to the ICU for clinical and hemodynamic monitoring, but the patient's condition in the ICU worsened. The patient experienced acute kidney failure and liver failure, then the patient died on the 10th day after surgery.Discussion: Surgery for ruptured abdominal aortic aneurysm is associated with high mortality. Even patients who survive the initial procedure are at high risk of complications (such as renal, cardiac, respiratory, haematological, or gastrointestinal failure). The main goal of anesthesia is to maintain anesthesia with cardiovascular stability and normothermia for as long as possible. Minimum standards of monitoring for surgery include electrocardiogram, CVP, arterial line, temperature, and urine output. This operation uses a cell saver machine which functions to collect lost blood, clean the blood and return it to the patient.Conclusion: Surgery for patients with acute aortic rupture requires complicated and complex anesthetic techniques. This operation requires collaboration and good communication between the surgeon and the anesthesiologist.

Protective effect of clotrimazole on lung injury in an experimental model of ruptured abdominal aortic aneurysm.

Lungs are the target organs most affected by ischemia/reperfusion (I/R) injury, which is exacerbated when hemorrhagic shock occurs. Suppressing various proinflammatory cytokines, inflammation and oxidation that initiate and aggravate lung damage with various drugs or methods provides significant benefits in preventing lung damage. This study aims to evaluate the protective effect of clotrimazole (CLT), an antimycotic drug, on lung injury and systemic inflammatory response in rats by creating an experimental model of a ruptured abdominal aortic aneurysm (RAAA). Thirty-six male Sprague Dawley rats were randomly divided into 5 groups: sham, sham+CLT, sham+polyethylene glycol (PEG), shock+ischemia/reperfusion (SIR), and SIR+CLT. Saline, CLT and PEG were administered in the sham groups without shock and I/R. The hemorrhagic shock was developed in SIR groups by drawing blood for 1 h to keep the mean arterial pressure at 50 mm Hg. After 60 min, the SIR+CLT group was given 20 mg/kg CLT; then, the aortic clamps were opened, and rats were left for 120 min of reperfusion. The blood taken to create hemorrhagic shock was returned in a controlled manner during this time. At the end of the reperfusion procedure, samples were taken for cytokine levels in serum and lung tissue and for other biochemical analyses. Blood gas, histopathological examination and wet/dry weight measurements were performed to assess lung injury. An increase was observed in all parameters in the SIR group compared to the sham group. In the SIR+CLT group, the serum myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-α), lung MPO values, histologically lung injury scores, and lung tissue wet/dry ratio were decreased significantly when compared to the SIR group (p < 0.05). These results indicate that CLT may reduce the systemic inflammatory response and lung injury due to shock and I/R in an experimental model of RAAA.

Evaluation of associations between outflow morphology and rupture risk of abdominal aortic aneurysms

PurposeThis study aimed to evaluate the association between the outflow morphology and abdominal aortic aneurysm (AAA) rupture risk, to find risk factors for future prediction models. Materials and methodsWe retrospectively analyzed 46 patients with ruptured AAAs and 46 patients with stable AAAs using a 1:1 match for sex, age, and maximum aneurysm diameter. The chi-square test, paired t-test, and Wilcoxon signed-rank test were used to compare variables. Logistic regression was performed to evaluate variables potentially associated with AAA rupture. Receiver operating characteristic curve analysis and the area under the curve (AUC) were used to assess the regression models. ResultsRuptured AAAs had a shorter proximal aortic neck (median (interquartile range, IQR): 24.0 (9.4–34.2) mm vs. 33.3 (20.0–52.8) mm, p = 0.004), higher tortuosity (median(IQR): 1.35 (1.23–1.49) vs. 1.29 (1.23–1.39), p = 0.036), and smaller minimum luminal area of the right common iliac artery (CIA) (median (IQR): 86.7 (69.9–126.4) mm2 vs. 118.9 (86.3–164.1)mm2, p = 0.001) and left CIA (median(IQR): 92.2 (67.3,125.1) mm2 vs. 110.7 (80.12, 161.1) mm2, p = 0.010) than stable AAA did. Multiple regression analysis demonstrated significant associations of the minimum luminal area of the bilateral CIAs (odds ratio [OR] = 0.996, 95 % confidence interval [CI] 0.991–0.999, p = 0.037), neck length (OR = 0.969, 95 % CI 0.941–0.993, p = 0.017), and aneurysm tortuosity (OR = 1.031, 95 % CI 1.003–1.063, p = 0.038) with ruptured AAAs. The AUC of this regression model was 0.762 (95 % CI 0.664–0.860, p < 0.001). ConclusionsThe smaller minimum luminal area of the CIA is associated with an increased risk of rupture. This study highlights the potential of utilizing outflow parameters as novel and additional tools in risk assessment. It also provides a compelling rationale to further intensify research in this area.

The Role of Integrated Air Transport System in Managing Patients with Abdominal Aortic Aneurysm Rupture

Ruptured abdominal aortic aneurysms (rAAAs) are highly morbid emergencies. Not all hospitals are equipped to repair them, and an air ambulance network may aid in regionalising speciality care to quaternary referral centres. The association of travel distance by air ambulance on rAAA mortality in patients transferred emergently for repair was examined. A retrospective review of institutional data. Adults with rAAA (2002 - 2019) transferred from an outside hospital (OSH) to a single quaternary referral centre for repair via air ambulance were identified. Patients who arrived via ground transport or post-repair at OSH for continued critical care were excluded. Patients were divided into "near" and "far" groups based on the 75th percentile of straight line travel distance (> 72 miles) between hospitals. The primary outcome was 30 day mortality. Multivariate logistic regression was used to assess the association of distance with mortality after adjusting for age, sex, race, cardiovascular comorbidities, and repair type. A total of 290 patients with rAAA were transported a median distance of 40.4 miles (interquartile range 25.5, 72.7) with 215 (74.1%) near and 75 (25.9%) far patients. Both near and far groups had similar ages, sex, and race. There was no difference in pre-operative loss of consciousness, intubation, or cardiac arrest between groups. Endovascular aneurysm repair utilisation and intra-operative aortic occlusion balloon usage were also similar. Both observed (26.8% vs. 23.9%, p = .61) and adjusted odd ratio (0.70, 95% confidence interval 0.36 - 1.39, p = .32) 30 day mortality did not differ significantly between near and far groups. Increasing distance travelled during transfer by air ambulance was not associated with worse outcomes in patients with rAAA. The findings support the regionalisation of rAAA repair to large quaternary centres via an integrated and robust air ambulance network.

Emergency Treatment of Ruptured Abdominal Aneurysm

Introduction: Abdominal aneurysm is considered a formidable pathological condition that requires prompt treatment. Its progressive increase leads to rupture and massive internal bleeding, which requires the most effective medical care. However, despite the improvement in medical equipment and postoperative care, mortality due to ruptured abdominal aneurysms is still close to 50%, which is primarily related to the severity of the pathology and open surgical intervention.&#x0D; Materials and Methods: 46 patients diagnosed with rupture of the abdominal aorta took part in the study. Selection criteria were a history of abdominal aortic rupture, conservative/operative treatment for the disease, and absence of other complications (acute renal failure, liver infarction) that could affect the results of the study.&#x0D; Results: Since January 2018, 46 cases of ruptured AAAs have been diagnosed. In all forty-six cases, surgical intervention was used: open surgery or endovascular technique. All 100% of patients had a previous history of diagnosed abdominal aortic aneurysm, for which they underwent periodic ultrasound examinations.&#x0D; As a result of the study, it was found that endovascular aortic aneurysm correction is the optimal method for both planned and emergency treatment of aortic aneurysm and its rupture. According to the Cochrane Specialized Register, it was established that endovascular repair is associated with a reduction in early morbidity and mortality after abdominal aneurysm, compared with other methods of surgical treatment. Furthermore, the study found that, unlike open surgery methods, endovascular techniques are associated with a lower risk of complications in the form of intestinal ischemia.&#x0D; Conclusions: Inferior quality studies and lack of information limit the conclusions of this review. From the statistical data shown in this paper, it can be concluded that there is a difference between endovascular and open methods of treatment of abdominal aortic aneurysm rupture. Mortality within the first 30 days after treatment and short-term complications are significantly lower in patients using EVAR. Systemic complications are also more prevalent in patients who were prescribed open surgical treatment.

Ketosis prevents abdominal aortic aneurysm rupture through C–C chemokine receptor type 2 downregulation and enhanced extracellular matrix balance

Abdominal aortic aneurysms (AAAs) are prevalent with aging, and AAA rupture is associated with increased mortality. There is currently no effective medical therapy to prevent AAA rupture. The monocyte chemoattractant protein (MCP-1)/C–C chemokine receptor type 2 (CCR2) axis critically regulates AAA inflammation, matrix-metalloproteinase (MMP) production, and extracellular matrix (ECM) stability. We therefore hypothesized that a diet intervention that can modulate CCR2 axis may therapeutically impact AAA risk of rupture. Since ketone bodies (KBs) can trigger repair mechanisms in response to inflammation, we evaluated whether systemic ketosis in vivo could reduce CCR2 and AAA progression. Male Sprague–Dawley rats underwent surgical AAA formation using porcine pancreatic elastase and received daily β-aminopropionitrile to promote AAA rupture. Rats with AAAs received either a standard diet, ketogenic diet (KD), or exogenous KBs (EKB). Rats receiving KD and EKB reached a state of ketosis and had significant reduction in AAA expansion and incidence of rupture. Ketosis also led to significantly reduced aortic CCR2 content, improved MMP balance, and reduced ECM degradation. Consistent with these findings, we also observed that Ccr2−/− mice have significantly reduced AAA expansion and rupture. In summary, this study demonstrates that CCR2 is essential for AAA expansion, and that its modulation with ketosis can reduce AAA pathology. This provides an impetus for future clinical studies that will evaluate the impact of ketosis on human AAA disease.

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 (&lt;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.

Suppression of Inflammation-induced Abdominal Aortic Aneurysm Formation by Induction of Elastin Tolerance

Abdominal aortic aneurysm (AAA) is a vascular disease process whereby the aorta expands to apoint where rupture may occur. This serious condition is diagnosed in approximately 200,000 people in the United States per year and accounts for over 15,000 deaths annually. The only medical intervention proven to reduce the risk of AAA rupture is surgical repair; however, such repair is associated with high risk of death, reduced quality of life, and high expense. AAA is caused by the weakening of the artery wall due to inflammation-induced destruction of its structural components. Our clinical data shows increased levels of circulating elastin degradation products in patients with AAA, especially smokers, compared to risk factor matched controls. This observation led us to hypothesize that an immune reaction to elastin fragments initiates the inflammatory cascade in the aorta that leads to AAA formation. To test this hypothesis, C57BL/6 mice were injected with poly(lactide-co-glycolide) nanoparticle-encapsulated IL-10 to induce immune tolerance or nanoparticle-encapsulated control ovalbumin. Injection of elastin fragments was performed 7 days later to induce an immune response. AAA of the infrarenal aorta was induced by topical application of elastase during laparotomy procedure 14 days after nanoparticle injection. Aorta diameter was measured 16 days post-operatively with Microfil. Immunologic changes were evaluated by cytokine analysis, Tr1/Th17 cell ratio inperipheral blood, and splenic Th17 and Tr1 response to elastin. Based on prior work, we expect that induction of elastin tolerance using poly(lactide-co-glycolide) nanoparticle-encapsulated IL-10 will suppress abdominal aortic aneurysm expansion and promote an anti-inflammatoryenvironment characterized by increased Tr1/Th17 cell ratio, increased levels of anti-inflammatory cytokines, and decreased pro-inflammatory cytokine expression.

Size thresholds for repair of abdominal aortic aneurysms warrant reconsideration

BackgroundThe historical size threshold for abdominal aortic aneurysm (AAA) repair is widely accepted to be 5.5 cm for men and 5.0 cm for women. However, contemporary AAA rupture risks may be lower than historical benchmarks, which has implications for when AAAs should be repaired. Our objective was to use contemporary AAA rupture rates to inform optimal size thresholds for AAA repair. MethodsWe used a Markov chain analysis to estimate life expectancy for patients with AAA. The primary outcome was AAA-related mortality. We estimated survival using Social Security Administration life tables and published contemporary AAA rupture estimates. For those undergoing repair, we modified survival estimates using data from the Vascular Quality Initiative and Medicare on complications, late rupture, and open conversion. We used this model to estimate the AAA repair size threshold that minimizes AAA-related mortality for 60-year-old average-health men and women. We performed a sensitivity analysis of poor-health patients and 70- and 80-year-old base cases. ResultsThe annual risk of all-cause mortality under surveillance for a 60-year-old woman presenting with a 5.0 cm AAA using repair thresholds of 5.5 cm, 6.0 cm, 6.5 cm, and 7.0 cm was 1.7%, 2.3%, 2.7%, and 2.8%, respectively. The corresponding risk for a man was 2.3%, 2.9%, 3.3%, and 3.4% for the same repair thresholds, respectively. For a 60-year-old average-health woman, an AAA repair size of 6.1 cm was the optimal threshold to minimize AAA-related mortality. Life expectancy varied by <2 months for repair at sizes from 5.7 cm to 7.1 cm. For a 60-year-old average-health man, an AAA repair size of 6.9 cm was the optimal threshold to minimize AAA-related mortality. Life expectancy varied by <2 months for repair at sizes from 6.0 cm to 7.4 cm. Women in poor health, at various age strata, had optimal AAA repair size thresholds that were >6.5 cm, whereas men in poor health, at all ages, had optimal repair size thresholds that were >8.0 cm. ConclusionsThe optimal threshold for AAA repair is more nuanced than a discrete size. Specifically, there appears to be a range of AAA sizes for which repair is reasonable to minmized AAA-related mortality. Notably, they all are greater than current guideline recommendations. These findings would suggest that contemporary AAA size thresholds for repair should be reconsidered.

An Endovascular Approach to Abdominal Aortic Aneurysm Rupture is Associated With Improved Outcomes for Patients With Prior Aortic Repair

To assess whether outcomes of rupture repair differ by aortic repair history and determine the ideal approach for rupture repair in patients with previous aortic repair. This retrospective review included all patients who underwent repair of a ruptured infrarenal abdominal aortic aneurysm from 2003 - 2021 recorded in the Vascular Quality Initiative (VQI) registry. Pre-operative characteristics and post-operative outcomes and long term survival were compared between patients without prior aortic repair. To assess the impact of open and endovascular approaches to rupture, a subgroup analysis was then performed among patients who ruptured after a prior infrarenal aortic repair. Univariable and adjusted analyses were performed to account for differences in patient characteristics and operative details. A total of 6 197 patients underwent rupture repair during the study period, including 337 (5.4%) with prior aortic repairs. Univariate analysis demonstrated increased 30 day mortality in patients with prior repairs versus without (42 vs. 36%; p = .034), and prior repair was associated with increased post-operative renal failure (35 vs. 21%; p < .001), respiratory complications (32 vs. 24%; p < .001), and wound complications (9 vs. 4%; p < .001). Following adjustment, all outcomes were similar with the exception of bowel ischaemia, which was decreased among patients with prior repair (OR 0.7, 95% CI 0.6 - 0.9). Subgroup analysis demonstrated that patients with a prior aortic repair history who underwent open rupture repair had increased odds for 30 day mortality (OR 1.3, 95% CI 1.2 - 1.7) and adverse secondary outcomes compared with those managed endovascularly. Prior infrarenal aortic repair was not independently associated with increased morbidity or mortality following rupture repair. Patients with a prior aortic repair history demonstrated statistically significantly higher mortality and morbidity when treated with an open repair compared with endovascular approach. An endovascular first approach to rupture should be strongly encouraged whenever feasible in patients with prior aortic repair.

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.

Influence of cardiometabolic medications on abdominal aortic aneurysm growth in the UK Aneurysm Growth Study: metformin and angiotensin-converting enzyme inhibitors associated with slower aneurysm growth.

There is a clinical need for treatments that can slow or prevent the growth of an abdominal aortic aneurysm, not only to reduce the need for surgery, but to provide a means to treat those who cannot undergo surgery. Analysis of the UK Aneurysm Growth Study (UKAGS) prospective cohort was conducted to test for an association between cardiometabolic medications and the growth of an abdominal aortic aneurysm above 30 mm in diameter, using linear mixed-effect models. A total of 3670 male participants with data available on abdominal aortic aneurysm growth, smoking status, co-morbidities, and medication history were included. The mean age at recruitment was 69.5 years, the median number of surveillance scans was 6, and the mean(s.e.) unadjusted abdominal aortic aneurysm growth rate was 1.75(0.03) mm/year. In a multivariate linear mixed-effect model, smoking (mean(s.e.) +0.305(0.07) mm/year, P = 0.00003) and antiplatelet use (mean(s.e.) +0.235(0.06) mm/year, P = 0.00018) were found to be associated with more rapid abdominal aortic aneurysm growth, whilst metformin was strongly associated with slower abdominal aortic aneurysm growth (mean(s.e.) -0.38(0.1) mm/year, P = 0.00019), as were angiotensin-converting enzyme inhibitors (mean(s.e.) -0.243(0.07) mm/year, P = 0.0004), angiotensin II receptor antagonists (mean(s.e.) -0.253(0.08) mm/year, P = 0.00255), and thiazides/related diuretics (mean(s.e.) -0.307(0.09) mm/year, P = 0.00078). The strong association of metformin with slower abdominal aortic aneurysm growth highlights the importance of the ongoing clinical trials assessing the effectiveness of metformin with regard to the prevention of abdominal aortic aneurysm growth and/or rupture. The association of angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and diuretics with slower abdominal aortic aneurysm growth points to the possibility that optimization of cardiovascular risk management as part of abdominal aortic aneurysm surveillance may have the secondary benefit of also reducing abdominal aortic aneurysm growth rates.

A Greek Multicentre Study Assessing the Outcome of Late Rupture After Endovascular Abdominal Aortic Aneurysm Repair

Late rupture after endovascular aortic aneurysm repair (EVAR) for an abdominal aortic aneurysm (AAA) is an increasing complication associated with high mortality. This study aimed to analyse the causes and outcomes in patients with AAA rupture after EVAR. A multi-institutional Greek study of late ruptures after EVAR between 2008 - 2022 was performed. Primary outcomes were intra-operative and in hospital mortality. A total of 70 patients presented with late rupture after EVAR (proportion of ruptured EVARs among all EVARs, 0.6%; 69 males; mean age 77.2 ± 6.7 years). The mean time interval between EVAR and late rupture was 72.3 months (range 6 - 180 months). In all cases the cause of rupture was the presence of endoleak (type I, 73%) with sac enlargement. Moreover, 34% of subjects with rupture after EVAR were lost to follow up and 32% underwent a secondary intervention. Additionally, 57 patients (81%) were treated with conversion to open surgical repair (COSR) and the remainder with endovascular correction of endoleak (ECE). Eleven intra-operative deaths (16%) were recorded. The overall in hospital mortality rate was 41% (23% ECE vs. 46% COSR; p = .21). Of the patients who presented as initially haemodynamically stable, 23% died during hospitalisation, while the respective mortality rate for patients who presented as unstable was 78% (odds ratio [OR] 11.8, 95% confidence interval [CI] 3.6 - 39.1; p < .001). Multivariate logistic regression analysis revealed that severity of haemodynamic shock was the most significant risk factor for intra-operative death (OR 7.15, 95% CI 1.58 - 32.40; p = .010) and in hospital mortality (OR 9.53, 95% CI 2.79 - 32.58; p < .001). These data underline the devastating prognosis of late rupture after EVAR. Haemodynamic status at presentation was an important predictive factor for mortality both in the ECE and COSR groups. Rigorous follow up and prompt evaluation of an unstable patient in case of rupture after EVAR is recommended.

Ganglioside GM3 Protects Against Abdominal Aortic Aneurysm by Suppressing Ferroptosis.

Abdominal aortic aneurysm (AAA) is a potentially life-threatening vascular condition, but approved medical therapies to prevent AAA progression and rupture are currently lacking. Sphingolipid metabolism disorders are associated with the occurrence and development of AAA. It has been discovered that ganglioside GM3, a sialic acid-containing type of glycosphingolipid, plays a protective role in atherosclerosis, which is an important risk factor for AAA; however, the potential contribution of GM3 to AAA development has not been investigated. We performed a metabolomics study to evaluated GM3 level in plasma of human patients with AAA. We profiled GM3 synthase (ST3GAL5) expression in the mouse model of aneurysm and human AAA tissues through Western blotting and immunofluorescence staining. RNA sequencing, affinity purification and mass spectrometry, proteomic analysis, surface plasmon resonance analysis, and functional studies were used to dissect the molecular mechanism of GM3-regulating ferroptosis. We conditionally deleted and overexpressed St3gal5 in smooth muscle cells (SMCs) in vivo to investigate its role in AAA. We found significantly reduced plasma levels of GM3 in human patients with AAA. GM3 content and ST3GAL5 expression were decreased in abdominal aortic vascular SMCs in patients with AAA and an AAA mouse model. RNA sequencing analysis showed that ST3GAL5 silencing in human aortic SMCs induced ferroptosis. We showed that GM3 interacted directly with the extracellular domain of TFR1 (transferrin receptor 1), a cell membrane protein critical for cellular iron uptake, and disrupted its interaction with holo-transferrin. SMC-specific St3gal5 knockout exacerbated iron accumulation at lesion sites and significantly promoted AAA development in mice, whereas GM3 supplementation suppressed lipid peroxidation, reduced iron deposition in aortic vascular SMCs, and markedly decreased AAA incidence. Together, these results suggest that GM3 dysregulation promotes ferroptosis of vascular SMCs in AAA. Furthermore, GM3 may constitute a new therapeutic target for AAA.