High proportion of undiagnosed diabetes in patients surgically treated for infrarenal abdominal aortic aneurysm: findings from the multicentre Norwegian Aortic Aneurysm and Diabetes (ABANDIA) Study.

BACKGROUND: The aim was to investigate the total prevalence of known and undiagnosed diabetes mellitus (DM), and the association of DM with perioperative complications following elective, infrarenal, open surgical (OSR) or endovascular (EVAR), Abdominal Aortic Aneurysm (AAA) repair. METHODS: In this Norwegian prospective multicentre study, 877 patients underwent preoperative screening for DM by HbA1c measurements from November 2017 to December 2020. Diabetes was defined as screening detected HbA1c ≥ 48 mmol/mol (6.5%) or previously diagnosed diabetes. The association of DM with in-hospital complications, length of stay, and 30-day mortality rate were evaluated using adjusted and unadjusted logistic regression models. RESULTS: The total prevalence of DM was 15% (95% CI 13%,17%), of which 25% of the DM cases (95% CI 18%,33%) were undiagnosed upon admission for AAA surgery. The OSR to EVAR ratio was 52% versus 48%, with similar distribution among DM patients, and no differences in the prevalence of known and undiagnosed DM in the EVAR versus the OSR group. Total 30-day mortality rate was 0.6% (5/877). Sixty-six organ-related complications occurred in 58 (7%) of the patients. DM was not statistically significantly associated with a higher risk of in-hospital organ-related complications (OR 1.23, 95% CI 0.57,2.39, p = 0.57), procedure-related complications (OR 1.48, 95% CI 0.79,2.63, p = 0.20), 30-day mortality (p = 0.09) or length of stay (HR 1.06, 95% CI 0.88,1.28, p = 0.54). According to post-hoc-analyses, organ-related complications were more frequent in patients with newly diagnosed DM (n = 32) than in non-DM patients (OR 4.92; 95% CI 1.53,14.3, p = 0.005). CONCLUSION: Twenty-five percent of all DM cases were undiagnosed at the time of AAA surgery. Based on post-hoc analyses, undiagnosed DM seems to be associated with an increased risk of organ related complications following AAA surgery. This study suggests universal DM screening in AAA patients to reduce the number of DM patients being undiagnosed and to improve proactive diabetes care in this population. The results from post-hoc analyses should be confirmed in future studies.

Risk factors and associated outcomes of postoperative delirium after open abdominal aortic aneurysm repair.

OBJECTIVE: Open abdominal aortic aneurysm repair (OAR) is a major vascular procedure that incurs a large physiologic demand, increasing the risk for complications such as postoperative delirium (POD). We sought to characterize POD incidence, identify delirium risk factors, and evaluate the effect of delirium on postoperative outcomes. We hypothesized that POD following OAR would be associated with increased postoperative complications and resource utilization. METHODS: This was a retrospective study of all OAR cases from 2012 to 2020 at a single tertiary care center. POD was identified via a validated chart review method based on key words and Confusion Assessment Method assessments. The primary outcome was POD, and secondary outcomes included length of stay, non-home discharge, 90-day mortality, and 1-year survival. Bivariate analysis as appropriate to the data was used to assess the association of delirium with postoperative outcomes. Multivariable binary logistic regression was used to identify risk factors for POD and Cox regression for variables associated with worse 1-year survival. RESULTS: Overall, 198 OAR cases were included, and POD developed in 34% (n = 67). Factors associated with POD included older age (74 vs 69 years; P < .01), frailty (50% vs 28%; P < .01), preoperative dementia (100% vs 32%; P < .01), symptomatic presentation (47% vs 27%; P < .01), preoperative coronary artery disease (44% vs 28%; P = .02), end-stage renal disease (89% vs 32%; P < .01) and Charlson Comorbidity Index score >4 (42% vs 26%; P = .01). POD was associated with 90-day mortality (19% vs 5%; P < .01), non-home discharge (61% vs 30%; P < .01), longer median hospital length of stay (14 vs 8 days; P < .01), longer median intensive care unit length of stay (6 vs 3 days; P < .01), postoperative myocardial infarction (7% vs 2%; P = .045), and postoperative pneumonia (19% vs 8%; P = .01). On multivariable analysis, risk factors for POD included older age, history of end-stage renal disease, lack of epidural, frailty, and symptomatic presentation. A Cox proportional hazards model revealed that POD was associated with worse survival at 1 year (hazard ratio, 3.8; 95% confidence interval, 1.6-9.0; P = .003). CONCLUSIONS: POD is associated with worse postoperative outcomes and increased resource utilization. Future studies should examine the role of improved screening, implementation of delirium prevention bundles, and multidisciplinary care for the most vulnerable patients undergoing OAR.

Acute kidney injury in patients undergoing endovascular or open repair of juxtarenal or pararenal aortic aneurysms.

BACKGROUND: The aim of this cohort study was to report the proportion of patients who develop periprocedural acute kidney injury (AKI) after endovascular repair (ER) and open surgery (OS) in patients with juxta/pararenal abdominal aortic aneurysm and to assess potential risk factors for AKI. The study also aimed to report the short- and long-term outcomes of patients with and without AKI. METHODS: This was a multicenter cohort study of five European academic high-volume centers (>50 OS or 50 ER infrarenal AAA repairs, plus >15 complex AAA repairs per year). All consecutively treated patients were extracted from a prospective vascular surgical registry and the data were scrutinized retrospectively. The primary end point for this study was the development of AKI. AKI was diagnosed when there is a two-fold increase of serum creatinine or decrease of glomerular filtration rate of >50% within 1 week of AAA repair. Secondary end points included long-term mortality and end-stage renal disease (ESRD). RESULTS: AKI occurred in 16.6% of patients in the ER group vs 30.3% in the OS group (P < .001). The 30-day mortality rate was higher among patients with AKI in both ER (15.4% vs 3.1%; P = .006) and OS (13.2% vs 5.3%; P = .001) groups. Age, chronic kidney disease, presence of significant thrombus burden in the pararenal region, >1000 mL blood loss in ER group were associated with development of AKI. Age, diabetes mellitus, chronic kidney disease, presence of significant thrombus burden in the pararenal region, and a proximal clamping time of >30 minutes in the OS group were associated with the development of AKI, whereas renal perfusion during clamping was the protective factor against AKI development. After a median follow-up of 91 months, AKI was associated with higher mortality rates in both the ER group (58.9% vs 29.7%; P < .001) and the OS group (61.5% vs 27.3%; P < .001). After the same follow-up period, AKI was associated with a higher incidence of ESRD in both the ER group (12.8% vs 3.6%; P = .009) and the OS group (9.9% vs 2.9%; P < .001). CONCLUSIONS: The current study identified important pre and postoperative factors associated with AKI after juxta/pararenal abdominal aortic aneurysm repair. Patients with postoperative AKI had significantly higher short- and long term mortality and higher incidence of ESRD than patients without AKI.

Calprotectin as a new inflammatory marker of abdominal aortic aneurysm: A pilot study.

INTRODUCTION: Abdominal aortic aneurysm (AAA) is a relevant clinical problem due to the risk of rupture of progressively dilated infrarenal aorta. It is characterized by degradation of elastic fibers, extracellular matrix, and inflammation of the arterial wall. Though neutrophil infiltration is a known feature of AAA, markers of neutrophil activation are scarcely analyzed; hence, the main objective of this study. METHODS: Plasma levels of main neutrophil activation markers were quantified in patients with AAA and a double control group (CTL) formed by healthy volunteers (HV) and patients with severe atherosclerosis submitted for carotid endarterectomy (CE). Calprotectin, a cytoplasmic neutrophil protein, was quantified, by Western blot, in arterial tissue samples from patients with AAA and organ donors. Colocalization of calprotectin and neutrophil elastase was assessed by immunofluorescence. RESULTS: Plasma calprotectin and IL-6 were both elevated in patients with AAA compared with CTL (p ⩽ 0.0001) and a strong correlation was found between both molecules (p < 0.001). This difference was maintained when comparing with HV and CE for calprotectin but only with HV for IL-6. Calprotectin was also elevated in arterial tissue samples from patients with AAA compared with organ donors (p < 0.0001), and colocalized with neutrophils in the arterial wall. CONCLUSIONS: Circulating calprotectin could be a specific AAA marker and a potential therapeutical target. Calprotectin is related to inflammation and neutrophil activation in arterial wall and independent of other atherosclerotic events.

Identification and characterization of new candidates for abdominal aortic aneurysm screening in patients outside of current accepted guidelines.

BACKGROUND: Previous studies have identified groups of patients with abdominal aortic aneurysm (AAA) that fall outside of currently accepted screening guidelines. Population-based studies have found AAA screening would be cost-effective at a prevalence of 0.5% to 1.0%. The goal of this study was to determine the prevalence of AAA in patients that fall outside of the current screening guidelines. In addition, we analyzed outcomes of the groups with a prevalence of greater than 1%. METHODS: Using the TriNetX Analytics Network, several patient cohorts were abstracted with a diagnosis of ruptured or unruptured AAA based on previously identified groups with a potentially high risk for AAA that fall outside of currently accepted screening guidelines. Groups were also stratified by sex. For groups found to have a prevalence of greater than 1%, the unruptured patients were further analyzed for long-term rates of rupture and included male ever-smokers aged 45 to 65, male never-smokers aged 65 to 75, male never-smokers aged greater than 75, and female ever-smokers aged 65 or greater. Long-term mortality, stroke, and myocardial infarction rates were compared in patients with treated and untreated AAA after propensity score matching. RESULTS: We identified 148,279 patients across the four groups with a prevalence of AAA of greater than 1% with female ever-smokers aged 65 or older being the most prevalent (2.73%). In each of the four groups, the rate of AAA rupture increased every 5 years and all had rupture rates of greater than 1% at 10 years. Meanwhile, controls for each of these four subgroups without a previous AAA diagnosis had rupture rates between 0.090% and 0.013% at 10 years. Those who underwent repair of their AAA had decreased incidence of mortality, stroke, and myocardial infarction. Specifically, male ever-smokers aged 45 to 64 had a significant difference in incidence of mortality and myocardial infarction at 5 years and stroke at 1 and 5 years. CONCLUSIONS: Our analysis suggests male ever-smokers aged 45 to 65, male never-smokers aged 65 to 75, male never-smokers aged greater than 75, and female ever-smokers aged 65 or greater have a more than 1% prevalence of AAA and, therefore, may benefit from screening. Outcomes were significantly worse compared with well-matched controls in these groups.

One-year safety and effectiveness of the Alto abdominal stent graft in the ELEVATE IDE trial.

OBJECTIVE: This study reports the results of a prospective, multicenter trial designed to evaluate the safety and effectiveness of the polymer based Endologix Alto Stent Graft System in treating abdominal aortic aneurysms (AAAs), with sealing 7 mm below the top of the fabric in aortic neck diameters from 16 to 30 mm. METHODS: Seventy-five patients were treated with Alto devices between March 2017 and February 2018 in 16 centers in the United States for infrarenal AAAs (max diameter ≥5.0 cm in diameter or size increase by 0.5 cm in 6 months or diameter ≥1.5 times the adjacent normal aorta). Patients were followed for 30 days, 6 months, and 1 year by clinical evaluation and computed tomography and abdominal x-ray imaging. Treatment success was defined as technical success and freedom from AAA enlargement, migration, type I or III endoleak, AAA rupture or surgical conversion, stent graft stenosis, occlusion, kink, thromboembolic events, and stent fracture attributable to the device requiring secondary intervention through 12 months. Preoperative characteristics, perioperative variables, follow-up clinical evaluations, and radiographic examination results through the first 1 year were analyzed. RESULTS: The mean patient age was 73 years, with 93% of patients being male. The 30-day major adverse event rate was 5.3%. At 1 year, the primary endpoint was met with a treatment success rate of 96.7%. Through 1-year post-treatment, all-cause mortality was 4.0%. No AAA-related mortality occurred. AAA enlargement was 1.6%, type I endoleak rate was 1.4%, with 100% freedom from type III endoleaks, device migration, device fracture, stent occlusion, or AAA rupture. The device-related secondary intervention rate was 2.7%. CONCLUSIONS: This prospective study demonstrates the Endologix Alto is safe and effective in treating AAAs with appropriate anatomy at 1 year. The safety endpoint is met by a 5.3% 30-day major adverse event rate, whereas the effectiveness endpoint is met by a treatment success rate of 96%.

Long-term outcomes of the Endurant endograft in patients undergoing endovascular abdominal aortic aneurysm repair.

OBJECTIVE/BACKGROUND: To investigate the long-term outcomes after endovascular aneurysm repair (EVAR) in a real-world setting using the Endurant endograft (EG). METHODS: 184 EVAR candidates treated with the Endurant family EGs in a single vascular center were prospectively enrolled from January 2009 to December 2016. Kaplan-Meir estimates of long-term standardized primary and secondary outcome measures were performed. Per protocol, subgroup comparison analysis was performed in three groups: patients treated within instructions for use (in-IFU) vs patients treated outside IFU (outside-IFU), EVAR in patients receiving the Endurant proximal diameter 32 or 36 mm EG vs those receiving the <32 mm diameter EG and EVAR with various Endurant EG versions. RESULTS: The mean follow-up was 75.09 ± 37.9 months (range: 4.1-172 months). The median age of the patients was 72.96 ± 7.03 years (range: 55-88 years). A total of 177 patients were male (96.2%). Compliance with IFU was followed in 107 patients (58.2%). Overall survival was 69.5% and 48% at 5 and 8 years, respectively. Of the 102 all-cause deaths, 7 (6.9%) were aneurysm related. Six of these postimplant deaths occurred in patients presented with aneurysm rupture from type Ia or/and type Ib endoleak. At 5, 8, and 10 years of observation, freedom from aneurysm rupture, open surgical conversion, type I/III endoleak, any type of endoleak, aneurysm-related secondary intervention probabilities, and neck-related events were as follows: 98.1%, 95%, and 89.4%; 95.1%, 91.2%, and 85.7%; 93.6%, 87.3%, and 83.9%; 83.4%, 74%, and 70.9%; 89.8%, 76.7%, and 72%; and 96.3%, 90%, and 87.6%, respectively. Corresponding clinical success was 90%, 77.4%, and 68.4%, respectively. Patients treated outside-IFU had significantly higher risk of aneurysm rupture, open surgical conversion probability, occurrence of type I/III endoleak, and chance of reinterventions and lower clinical success probabilities compared with the in-IFU counterparts at 5 and 8 years. This statistical difference remained when type Ia endoleak or endoleak of any type was considered independently. In addition, it was stronger in patients having extreme anatomic boundaries (>1 hostile anatomic condition), when aneurysm-related death, aneurysm rupture, and clinical success at 5 years were considered. Overall proximal migration and limb occlusion were recorded in 1.1% and 4.9% of the patients, respectively. Overall reintervention rate was 17.4%. An increase in aneurysm sac diameter was observed in 12.5% of patients and was not related to IFU status. The Endurant version or the proximal EG diameter had no significant association with the chance of any complication or adverse event. CONCLUSIONS: The data confirmed the durability of the Endurant EG, achieving promising long-term outcomes in a real-world setting. However, its positive performance must be interpreted with caution in patients treated off-label especially those with extreme anatomic boundaries. In this cohort, some of EVAR advantages might be lost in the late future. Further similar studies are warranted.

Initial Clinical Experience With AneuFix Injectable Biocompatible Elastomer for Translumbar Embolization of Type 2 Endoleaks.

PURPOSE: The aim of this study was to assess the initial experience, technical success, and clinical benefit of AneuFix (TripleMed, Geleen, the Netherlands), a novel biocompatible and non-inflammatory elastomer that is directly injected into the aneurysm sac by a translumbar puncture in patients with a type II endoleak and a growing aneurysm. MATERIALS AND METHODS: A multicenter, prospective, pivotal study was conducted (ClinicalTrials.gov:NCT02487290). Patients with a type II endoleak and aneurysm growth (>5 mm) were included. Patients with a patent inferior mesenteric artery connected to the endoleak were excluded for initial safety reasons. The endoleak cavity was translumbar punctured with cone-beam computed tomography (CT) and software guidance. Angiography of the endoleak was performed, all lumbar arteries connected to the endoleak were visualized, and AneuFix elastomer was injected into the endoleak cavity and short segment of the lumbar arteries. The primary endpoint was technical success, defined as successful filling of the endoleak cavity with computed tomography angiography (CTA) assessment within 24 hours. Secondary endpoints were clinical success defined as the absence of abdominal aortic aneurysm (AAA) growth at 6 months on CTA, serious adverse events, re-interventions, and neurological abnormalities. Computed tomography angiography follow-up was performed at 1 day and at 3, 6, and 12 months. This analysis reports the initial experience of the first 10 patients treated with AneuFix. RESULTS: Seven men and 3 women with a median age of 78 years (interquartile range (IQR), 74-84) were treated. Median aneurysm growth after endovascular aneurysm repair (EVAR) was 19 mm (IQR, 8-23 mm). Technical success was 100%; it was possible to puncture the endoleak cavity of all treated patients and to inject AneuFix. Clinical success at 6 months was 90%. One patient showed 5 mm growth with persisting endoleak, probably due to insufficient endoleak filling. No serious adverse events related to the procedure or AneuFix material were reported. No neurological disorders were reported. CONCLUSION: The first results of type II endoleak treatment with AneuFix injectable elastomer in a small number of patients with a growing aneurysm show that it is technically feasible, safe, and clinically effective at 6 months. CLINICAL IMPACT: Effective and durable embolization of type II endoleaks causing abdominal aortic aneurysms (AAA) growth after EVAR is challenging. A novel injectable elastic polymer (elastomer) was developed, specifically designed to treat type II endoleaks (AneuFix, TripleMed, Geleen, the Netherlands). Embolization of the type II endoleak was performed by translumbar puncture. The viscosity changes from paste-like during injection, into an elastic implant after curing. The initial experience of this multicentre prospective pivotal trial demonstrated that the procedure is feasible and safe with a technical success of 100%. Absence of AAA growth was observed in 9 out of 10 treated patients at 6 months.

Short Term and Long Term Clinical Outcomes of Endovascular versus Open Repair for Juxtarenal and Pararenal Abdominal Aortic Aneurysms Using Propensity Score Matching: Results from Juxta- and pararenal aortic Aneurysm Multicentre European Study (JAMES).

OBJECTIVE: The aim of this study was to compare the short and long term clinical outcomes of endovascular (EVAR) vs. open surgical repair (OSR) of juxtarenal (JAAAs) and pararenal abdominal aortic aneurysms (PAAAs) in five high volume European academic centres. METHODS: This was a retrospective multicentre cohort study of five high volume European academic centres (> 50 open or 50 endovascular abdominal aortic aneurysm repairs annually) including 834 consecutive patients who were operated on and prospectively followed. Using propensity score matching (PSM) each patient who underwent OSR was matched with one patient who underwent EVAR in a 1:1 ratio (145 patients per group). The primary endpoint was long term all cause mortality, while the secondary endpoint was freedom from aortic related re-intervention. RESULTS: After a follow up of 87 months, no difference in overall survival between the two groups was observed (38.6% for EVAR vs. 42.1% for OSR; p = .88). Patients undergoing EVAR underwent aortic related re-interventions more frequently (24.1% vs. 6.9%; p < .001). Acute kidney injury (AKI) occurred more frequently in patients in the OSR group (40.7% vs. 24.8%; p = .006). However, most patients who suffered from AKI recovered without further progression to renal failure. In hospital (3.4% for EVAR vs. 4.1% for OSR; p = 1.0) and 30 day (4.1% for EVAR vs. 5.5% for OSR; p = .80) mortality rates did not differ between groups. CONCLUSION: Both open and endovascular treatment can be performed in high volume aortic centres with low short term mortality and morbidity rates, and good long term outcomes. These data provide useful information to help patients choose between the two procedures when both are feasible.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Circular RNA suppression of vascular smooth muscle apoptosis through the miR-545-3p/CKAP4 axis during abdominal aortic aneurysm formation.

BACKGROUND: Abdominal aortic aneurysms (AAA) are an important cause of cardiovascular deaths. The loss of vascular smooth muscle cells (VSMCs) has been reported to be related to the pathology of AAA. This study focused on investigating the function of circ_0002168 in VSMC apoptosis. METHODS: Levels of genes and proteins were measured by quantitative real-time-polymerase chain reaction (qRT-PCR) and Western blot. The growth of VSMCs was determined by using cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry and the evaluation of caspase-3 activity analysis, reactive oxygen species (ROS) production as well as lactate dehydrogenase (LDH) activity. The binding between miR-545-3p and circ_0002168 or Cytoskeleton-associated protein 4 (CKAP4) was confirmed by bioinformatics analysis, dual-luciferase reporter, RNA immunoprecipitation, and pull-down assays. RESULTS: Circ_0002168 decreased in the aortic tissues of patients with AAA. Functionally, ectopic overexpression of circ_0002168 dramatically induced proliferation and suppressed apoptosis in VSMCs. Mechanistically, circ_0002168 sequestered miR-545-3p to release CKAP4 expression via the ceRNA mechanism, indicating the circ_0002168/miR-545-3p/CKAP4 feedback loop in VSMCs. Increased miR-545-3p and a decreased CKAP4 expression were observed in patients with AAA. Rescue experiments showed that miR-545-3p reversed the protective effects of circ_0002168 on VSMC proliferation. Moreover, inhibition of miR-545-3p could restrain the apoptosis of VSMCs, which was abolished by CKAP4 silencing. CONCLUSION: Circ_0002168 has a protective effect on VSMC proliferation by regulating the miR-545-3p/CKAP4 axis, adding further understanding of the pathogenesis of AAA and a potential therapeutic approach in AAA management.

Presence of Helicobacter cinaedi in Atherosclerotic Abdominal Aortic Aneurysmal Wall.

Recently, the relationship between Helicobacter cinaedi (H. cinaedi) infection and several diseases, including cardiovascular and central nervous system disorders, bone and soft tissue disorders, and infectious abdominal aortic aneurysms (AAAs), has been reported. Moreover, H. cinaedi may be associated with arteriosclerosis. In the present study, we investigated the association between H. cinaedi infection and clinically uninfected AAAs. Genetic detection of H. cinaedi in the abdominal aneurysm wall was attempted in 39 patients with AAA undergoing elective open surgery between June 2019 and June 2020. DNA samples extracted from the arterial wall obtained during surgery were analyzed using nested polymerase chain reaction (PCR). The target gene region was the H. cinaedi-specific cytolethal distending toxin subunit B (cdtB). Nine (23.1%) of 39 patients showed positive bands corresponding to H. cinaedi, and further sequencing analyses demonstrated the presence of H. cinaedi DNAs in their aneurysm walls. In contrast, all the non-aneurysm arterial walls in our patients were negative for H. cinaedi. In conclusion, this is the first report of the detection of H. cinaedi in the walls of a clinically non-infectious AAA.

Artificial Intelligence Application to Screen Abdominal Aortic Aneurysm Using Computed tomography Angiography.

The aim of our study is to validate a totally automated deep learning (DL)-based segmentation pipeline to screen abdominal aortic aneurysms (AAA) in computed tomography angiography (CTA) scans. We retrospectively evaluated 73 thoraco-abdominal CTAs (48 AAA and 25 control CTA) by means of a DL-based segmentation pipeline built on a 2.5D convolutional neural network (CNN) architecture to segment lumen and thrombus of the aorta. The maximum aortic diameter of the abdominal tract was compared using a threshold value (30 mm). Blinded manual measurements from a radiologist were done in order to create a true comparison. The screening pipeline was tested on 48 patients with aneurysm and 25 without aneurysm. The average diameter manually measured was 51.1 ± 14.4 mm for patients with aneurysms and 21.7 ± 3.6 mm for patients without aneurysms. The pipeline correctly classified 47 AAA out of 48 and 24 control patients out of 25 with 97% accuracy, 98% sensitivity, and 96% specificity. The automated pipeline of aneurysm measurements in the abdominal tract reported a median error with regard to the maximum abdominal diameter measurement of 1.3 mm. Our approach allowed for the maximum diameter of 51.2 ± 14.3 mm in patients with aneurysm and 22.0 ± 4.0 mm in patients without an aneurysm. The DL-based screening for AAA is a feasible and accurate method, calling for further validation using a larger pool of diagnostic images towards its clinical use.

Association of Genetic Polymorphisms with Abdominal Aortic Aneurysm in the Processes of Apoptosis, Inflammation, and Cholesterol Metabolism.

Background and Objectives: This study aims to identify the minor allele of the single nucleotide polymorphisms (SNPs) DAB2IP rs7025486, IL6R rs2228145, CDKN2BAS rs10757278, LPA rs3798220, LRP1 rs1466535, and SORT1 rs599839 in order to assess the risk of abdominal aortic aneurysm (AAA) formation and define the linkage among these SNPs. Materials and Methods: A case-control study with AAA patients (AAA group) and non-AAA controls (control group) was carried out in a study population. DNA was isolated from whole blood samples; the SNPs were amplified using PCR and sequenced. Results: In the AAA group of 148 patients, 87.2% of the patients were male, 64.2% had a history of smoking, and 18.2% had relatives with AAA. The mean ± SD of age, BMI, and aneurysmal diameter in the AAA group were 74.8 ± 8.3 years, 27.6 ± 4.6 kg/m2, and 56.2 ± 11.8 mm, respectively. In comparison with 50 non-AAA patients, there was a significantly elevated presence of the SNPs DAB2IP rs7025486[A], CDKN2BAS rs10757278[G], and SORT1 rs599839[G] in the AAA group (p-values 0.040, 0.024, 0.035, respectively), while LPA rs3798220[C] was significantly higher in the control group (p = 0.049). A haplotype investigation showed that the SNPs DAB2IP, CDKN2BAS, and IL6R rs2228145[C] were significantly elevated in the AAA group (p = 0.037, 0.037, and 0.046) with minor allele frequencies (MAF) of 25.5%, 10.6%, and 15.4%, respectively. Only DAB2IP and CDKN2BAS showed significantly higher occurrences of a mutation (p = 0.028 and 0.047). Except for LPA, all SNPs were associated with a large aortic diameter in AAA (p < 0.001). Linkage disequilibrium detection showed that LPA to DAB2IP, to IL6R, to CDKN2BAS, and to LRP1 rs1466535[T] had D' values of 70.9%, 80.4%, 100%, and 100%, respectively. IL6R to LRP1 and to SORT1 had values for the coefficient of determination (r2) of 3.9% and 2.2%, respectively. Conclusions: In the investigated study population, the SNPs CDKN2BAS rs10757278, LPA rs3798220, SORT1 rs599839, DAB2IP rs7025486, and IL6R rs2228145 were associated with the development of abdominal aortic aneurysms. Individuals with risk factors for atherosclerosis and/or a family history of AAA should be evaluated using genetic analysis.

The Role of Immune Mechanisms in Abdominal Aortic Aneurysm: Could It be a Promising Therapeutic Strategy?

Abdominal aortic aneurysm (AAA) is an enlargement of the aorta greater than 50% in diameter. Although up to 80% of cases result in mortality if the aneurysm ruptures, patients are often diagnosed too late, as most cases are asymptomatic. The current treatment for AAA is still surgery as there are currently no effective drug treatments. Knowledge of the pathophysiological mechanisms is essential for the development of new preventive and therapeutic approaches. However, the molecular mechanisms are complex and remain unclear. Apoptosis of vascular smooth muscle cells, the major cellular component of the aorta, and degeneration of the extracellular matrix, the skeleton of the aortic wall, are hallmarks of AAA pathology. Inflammation, mainly through macrophage cells, has been recognized as a central factor in the development of AAA. Macrophage cells also orchestrate other pathways and immune cells involved in this process. Macrophages do not exist as pure populations at aneurysm sites. M1 macrophages are pro-inflammatory and weaken the aortic wall during AAA development. M2 macrophages, in contrast, are involved in anti-inflammatory reactions and aorta tissue repair. The balancing effect on AAA progression makes M1/M2 macrophages therapeutic targets to control inflammation and destruction of the aortic wall. An early diagnosis is also important to allow for early interventions. This review article, based on the available data, aims to evaluate the role of an immunotherapeutic approach in controlling AAA development by briefly discussing the immunological mechanisms.

The financial implications of cardiac stress testing prior to abdominal aortic aneurysm repair.

BACKGROUND: The utilization and cost-effectiveness of stress testing before abdominal aortic aneurysm (AAA) repair remains insufficiently studied. We examined the variation and financial implications of stress testing, and their association with major adverse cardiovascular events (MACE). METHODS: We studied patients who underwent elective endovascular (EVAR) or open AAA repair (OAR) at Vascular Quality Initiative centers from 2015 to 2019. We grouped centers into quintiles of preoperative stress testing frequency. We calculated the risk of postoperative MACE, a composite of in-hospital myocardial infarction, heart failure, or death, for each center-quintile. We obtained charges for stress tests locally and applied these to the cohort to estimate charges per 1000 patients. RESULTS: We studied 32,459 patients (EVAR: 27,978; OAR: 4481; 283 centers). Stress test utilization varied across quintiles from 13.0% to 68.6% (median: 36.8%) before EVAR and 15.9% to 85.0% (median: 59.4%) before OAR. The risk of MACE was 1.4% after EVAR and 10.2% after OAR. There was a trend towards more common MACE after EVAR among centers with higher utilization of stress testing: 0.9% among centers in the lowest quintile, versus 1.7% in the highest quintile (p-trend = 0.068). There was no association between MACE and stress testing frequency for OAR (p-trend = 0.223). The estimated financial charges for stress testing before EVAR ranged from $125,806 per 1000 patients at 1st-quintile centers, to $665,975 at 5th-quintile centers. Charges before OAR ranged from $153,861 at 1st-quintile centers, to $825,473 at 5th-quintile centers. CONCLUSION: Stress test use before AAA repair is highly variable and associated with substantial cost, with an unclear association with postoperative MACE. This highlights the need for improved stress testing paradigms prior to surgery.

The role of dipeptidyl peptidase-IV in abdominal aortic aneurysm pathogenesis: A systematic review.

Abdominal aortic aneurysm (AAA) is an important vascular disease carrying significant mortality implications due to the risk of aneurysm rupture. Current management relies exclusively on surgical repair as there is no effective medical therapy. A key element of AAA pathogenesis is the chronic inflammation mediated by inflammatory cells releasing proteases, including the enzyme dipeptidyl peptidase IV (DPP-IV). This review sought to recapitulate available evidence on the involvement of DPP-IV in AAA development. Further, we assessed the experimental use of currently available DPP-IV inhibitors for AAA management in murine models. Embase, Medline, PubMed, and Web of Science databases were utilised to access the relevant studies. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). A narrative synthesis approach was used. Sixty-four studies were identified from the searched databases; a final 11 were included in the analysis. DPP-IV was reported to be significantly increased in both AAA tissue and plasma of patients and correlated with AAA growth. DPP-IV inhibitors (sitagliptin, vildagliptin, alogliptin, and teneligliptin) were all shown to attenuate AAA formation in murine models by reducing monocyte differentiation, the release of reactive oxygen species (ROS), and metalloproteinases (MMP-2 and MMP-9). DPP-IV seems to play a role in AAA pathogenesis by propagating the inflammatory microenvironment. This is supported by observations of decreased AAA formation and reduction in macrophage infiltration, ROS, matrix MMPs, and interleukins following the use of DPP-IV inhibitors in murine models. There is an existing translational gap from preclinical observations to clinical trials in this important and novel mechanism of AAA pathogenesis. This prior literature highlights the need for further research on molecular targets involved in AAA formation.

Smaller size is more suitable for pharmacotherapy among undersized abdominal aortic aneurysm: A systematic review and meta-analysis.

Background: Pharmacotherapy for undersized abdominal aortic aneurysm (AAA) is a clinical unmet need. Randomized controlled trials (RCTs) have failed to show effectiveness despite countless promising data in preclinical studies. We aimed to identify the population with undersized AAAs (30-54 mm) who potentially benefit from pharmacotherapy. Methods: In accordance with the PRISMA statement, we conducted a systematic review and meta-analysis of placebo-controlled RCTs. The primary outcome was mean difference (MD) in annual growth rate (< 0 favors pharmacotherapy), and the secondary outcome was aneurysm-related events (diameters ⩾ 55 mm, ruptures, or referral to surgery). Results: Our search strategy identified eight RCTs (six trials on antibiotics [ABx], two on renin-angiotensin system inhibitors [RAS-I]) with a total of 1325 patients. The mean of baseline diameters ranged from 33.1 mm to 43.1 mm. Neither ABx nor RAS-I showed significant differences in MD. Multivariable random-effects restricted maximum likelihood meta-regression revealed a statistically significant linear relationship between baseline diameter and MD (coefficient 0.15 [95% CI 0.0011, 0.30], p = 0.049) but not for the follow-up period (p = 0.28) and duration of treatment (p = 0.11). In line with this result, ABx with baseline diameter < 40 mm significantly reduced MD (-1.03 mm/year [95% CI -1.64, -0.42], p = 0.001) and a borderline significant difference in aneurysm-related events (HR 0.53 [95% CI 0.28, 1.00], p = 0.05), whereas the other groups ⩾ 40 mm never demonstrated effectiveness. Fixed-effect models did not change the results. No evidence of publication bias was detected. Conclusion: Undersized AAAs < 40 mm can potentially benefit from pharmacotherapy. Future RCTs should consider preferentially including undersized AAA with smaller diameters.

Mechanisms of abdominal aortic aneurysm progression: A review.

Abdominal aortic aneurysm (AAA) is a common disease associated with significant cardiovascular morbidity and mortality. Up to now, there is still controversy on the choice of treatment method of AAA. Even so, the mechanisms of AAA progression are poorly defined, making targeting new therapies problematic. Current evidence favors an interaction of the hemodynamic microenvironment with local and systemic immune responses. In this review, we aim to provide an update of mechanisms in AAA progression, involving hemodynamics, perivascular adipose tissue, adventitial fibroblasts, vasa vasorum remodeling, intraluminal thrombus, and distribution of macrophage subtypes.

Mycobacterium Bovis Causing Mycotic Aneurysm Secondary to Intravesical Treatment with Bacillus Calmette-Guérin: A Case Report.

BACKGROUND: Bacillus Calmette-Guerin (BCG) is a live, attenuated strain of Mycobacterium bovis that is used in the treatment of non-muscle invasive bladder cancer (NMIBC). Vascular complications, including mycotic aneurysms, after BCG therapy are exceedingly rare. In this patient population, the diagnosis of mycotic aneurysms can be delayed or missed due to their non-specific clinical and radiologic presentation. Literature review reveals management of mycotic aneurysms attributable to BCG therapy is widely varied.2,5-8,12,15 CASE REPORT: We report a patient who presented with mycotic aneurysm formation secondary to BCG treatment for bladder cancer that was repaired with in-line reconstruction utilizing cryoartery and buttressed with omental flap. We suggest this as an alternative treatment to in-line prosthetic graft or extra-anatomic reconstruction.