This single-center prospective observational follow-up study aimed to evaluate 2-year changes in carotid plaque volume and echogenicity and to explore whether clinical and biochemical baseline factors are associated with plaque progression. It was an exploratory observational follow-up of patients with echolucent plaques previously enrolled in a 12-month randomized controlled trial. Plaque volume and grayscale median were measured at baseline and at 3, 6, 12, and 24 months using three-dimensional ultrasound (3D-US). Associations between baseline characteristics and plaque progression were evaluated using mixed-effects models with time-predictor interactions, adjusted for baseline plaque volume. Medication adherence from 12 to 24 months was examined. Plaque echogenicity remained stable over 24 months, whereas mean plaque volume increased with heterogeneous patterns. Approximately 20% of plaques were classified as progressors, 70% as stable, and 10% as regressors. Higher mean arterial pressure, low density lipoprotein cholesterol (LDL-C), and larger baseline volume were significantly associated with plaque progression. Poor statin adherence showed a non-significant trend toward greater progression. In conclusion, echolucent carotid plaques demonstrated stable echogenicity but volumetric progression over 24 months. Blood pressure, LDL-C, and baseline plaque size were associated with progression, although limited by sample size, supporting a role for longitudinal 3D-US plaque volume assessment in individualized cardiovascular prevention.

OBJECTIVE:Surveillance of abdominal aortic aneurysms (AAAs) traditionally relies on diameter measurements, yet up to 10% of ruptures occur below repair thresholds. The relationship between localised wall strain and future AAA growth remains unexplored. This study aimed to examine localised AAA wall strain patterns and their association with aneurysm growth. METHODS:This was a prospective study of patients with an infrarenal AAA under surveillance with conventional ultrasound. In a standard examination, ten second ultrasound videos (cineloops) were acquired in transverse plane with the curved array transducer at the maximum anteroposterior diameter during breath hold. From these cineloops, strain patterns were extracted and analysed via functional data analysis to assess changes over time and associations with annual AAA diameter growth. RESULTS:Two hundred and seventy-eight patients (median age 73 years; 238 men) across 1 117 clinic visits were included, with a median follow up of 2.3 years. Progressive vessel wall stiffening and increasingly homogeneous strain patterns were observed over time (p < .001). Baseline strain patterns were statistically significantly associated with future AAA growth (p = .006), especially in specific regions. In the posterior left and right vessel wall, a 5% point increase in strain corresponded to a 31.9% and 6.7% higher annual growth rate, respectively. Conversely, the same increase at the anterior middle wall was linked to a 33.3% reduction in annual growth rate. These associations remained statistically significant after adjusting for baseline diameter, age, sex, smoking, hypertension, and diabetes (p = .041). CONCLUSION:Ultrasound strain mapping identified biomechanical regions linked to AAA progression. Strain patterns were associated with future growth independently of diameter, supporting their potential utility in complementing diameter in AAA monitoring and risk stratification.

Abdominal aortic aneurysm (AAA) is a potentially lethal condition if left untreated. AAA growth is a predictor of rupture as well as decreased survival. Minimally invasive infrarenal endovascular aortic repair (EVAR) is the primary option for AAA treatment. One of the most common complications after EVAR is the presence of type 2 endoleaks (T2ELs), i.e., continued retrograde perfusion of the aneurysm sac by aortic side branches, typically the lumbar arteries. In many cases, a T2EL prevents optimal aneurysm exclusion and is associated with continued aneurysm growth. Thus, a low but persistent risk of rupture and a high rate of reinterventions remain an issue/concern in the presence of T2ELs. In addition, failure of aneurysm sac shrinkage even without concomitant endoleak is associated with decreased long-term survival. Pre-emptive as well as postoperative selective side branch occlusion to prevent or treat T2ELs is time-consuming and technically demanding with a low technical and clinical success rate. Therefore, perioperative, nonselective embolization of the aneurysm sac during EVAR has been proposed to prevent T2EL and promote sac shrinkage (PREVAR—Clinical Trial NCT05575570). Patients scheduled for EVAR at the Department of Vascular Surgery, Rigshospitalet Copenhagen University Hospital, The Heart Center, Denmark, are offered inclusion in this study. Patients are randomized to infrarenal EVAR (control) or infrarenal EVAR plus sac embolization with Shape Memory plugs (SMP) (intervention). The plugs are based on a resorbable scaffolding and a small radiopaque marker causing minimal imaging artifacts on computed tomography angiography (CTA). The number of plugs is individually calculated based on aneurysm sac flow volume. Postoperative follow-up (FU) is performed after 3 months, 1 year, and 5 years with both contrast-enhanced ultrasound (CEUS) and 3-phase CTA (without contrast, arterial phase, and venous phase). AAA sac volume change is the primary endpoint. Incidence of T2EL, reintervention rate, and long-term survival are the secondary endpoints. The study is terminated after the final patient has completed the 5-year FU. EVAR has revolutionized AAA treatment since its introduction. In the short term, outcomes are superior to open aortic repair in anatomically suitable candidates. However, the high incidence of T2ELs and failure of AAA sac shrinkages associated with reinterventions and decreased survival in many patients. Preliminary data on intraoperative AAA sac embolization during EVAR seems to promote sac shrinkage. SMP plugs are tested and CE marked (Conformité Européenne) for embolization treatment but the effect of aneurysm sac embolization during EVAR is poorly known. This randomized study investigates the effect of aneurysm sac embolization with SMP plug material in a single-center setting. Clinical Trial, PREVAR—Clinical Trial NCT05575570, registered October 12, 2022, https://clinicaltrials.gov/study/NCT05575570.

Background:Aortic stiffness is a proxy for cardiovascular risk, but the methods are technically demanding. Ultrasound-based assessment of aortic wall strain patterns is established in abdominal aortic aneurysms but has never been described in the non-aneurysmal aorta. This study aimed to describe a workflow for ultrasound-derived strain mapping of the non-aneurysmal abdominal aorta and assess technical applicability, acquisition reproducibility, and age-related strain patterns. Methods:In this cross-sectional proof-of-concept study, healthy volunteers underwent ultrasound scanning of their non-aneurysmal abdominal aortas with standard equipment. Three independent operators scanned each participant. The ultrasound acquisitions were saved as short videos, or cine-loops, and were analysed off-line with prototype software to extract mean strain, strain heterogeneity, and circumferential strain patterns. Acquisition reproducibility was assessed with extended Bland-Altman statistics, and associations with age group and sex were analysed using regression models and functional data analysis. Results:Fifty-seven volunteers were included, generating 171 cineloops; all were suitable for strain analysis. Mean strain decreased with age from 8.70% in participants aged <30 years to 3.90% in those aged >50 years (P < .001), and strain heterogeneity was associated with age (P = .01). Mean strain and heterogeneity were not associated with sex. Inter-operator limits of agreement were ±1.5 mm for diameter, ±1.64 percentage points for mean strain, and ±0.18 for heterogeneity index. Conclusion:Ultrasound-derived strain mapping of the non-aneurysmal abdominal aorta is applicable and shows acceptable acquisition reproducibility. The method describes age-related differences in aortic strain, supporting validation as a future tool for assessing aortic stiffness and cardiovascular risk.

OBJECTIVE:The aim of this cross-sectional study was to assess the association between burnout and pain among vascular surgeons (VS) and vascular surgical trainees (VST) in Denmark. METHODS:In 2023, all clinically active VS/VST in Denmark were invited to participate in an anonymous survey consisting of validated questionnaires assessing burnout, perceived physical job demands, and pain. RESULTS:Of 111 VS/VST in Denmark, a response rate of 72% was obtained (n = 80). The majority were men (54%, n = 43) and VS (75%, n = 60). Associations between burnout and pain in the nine body regions assessed were statistically significant (p = .035 to < .001). Surgeons reporting frequent pain (weekly or more often) had statistically significantly higher burnout scores compared with surgeons reporting pain less often (monthly or never) (p = .029 to < .001). Pain was primarily reported in the neck/shoulders, back, and head, with different main pain areas depending on type of surgical procedure primarily performed (open, endovascular, endovenous). Pain during or after surgery was reported by 65% (n = 51), with frequency ranging from always (8%, n = 6), to often (24%, n = 19) and sometimes (33%, n = 26). The overall burnout prevalence (ranging from mild to severe) was 72% (n = 58), of whom 32% (n = 26) reported moderate to severe burnout symptoms. On a scale from 0 - 100, the mean burnout score was 37.7 (95% confidence interval [CI] 32.9 - 42.4) and varied between departments (p = .096) and job positions, with junior attendings reporting the highest levels of burnout (47.4, 95% CI 36.8 - 57.9) (attending vs. junior attending, p = .066; chief resident vs. resident, p = .58). Higher levels of perceived physical job demands were associated with higher levels of burnout (Pearson's r = 0.49). CONCLUSION:This national study showed that pain during or after surgery is frequent among VS/VST and that it is significantly associated with burnout. Creating work conditions that mitigate pain and burnout is essential to support occupational health and to maintain a robust vascular surgical service.

PurposeTo review the available evidence on the effectiveness and safety of bleomycin electrosclerotherapy (BEST) for slow-flow vascular malformations.Materials and MethodsA systematic review was conducted according to PRISMA guidelines, with a protocol registered in PROSPERO. Five databases were searched, supplemented by citation tracking, to identify peer-reviewed studies reporting clinical outcomes of BEST for slow-flow vascular malformations. Single-patient case reports were excluded. Two authors independently extracted data and assessed risk of bias.ResultsTen studies were included, with a total of 401 patients and 416 lesions. Seven studies were retrospective, three were prospective, and one was comparative. Any symptom improvement was reported in 62-100% of patients; however, outcome definitions and assessment methods varied substantially across studies, limiting direct comparability. Any size reduction was reported in 83-100% of lesions, based on clinical and imaging-based assessments, including volumetry. Serious adverse events were uncommon, and no systemic toxicity was reported. All non-randomised studies had serious risk of bias.ConclusionBEST appears promising for selected slow-flow vascular malformations. However, evidence is limited by methodological heterogeneity and high risk of bias, and treatment decisions should remain individualised and based on multidisciplinary evaluation.

Introduction: Simulation-based education (SBE) for endovascular aortic repair (EVAR) is typically delivered in simulation centres and workshops using standardised aortic anatomy. A logical next step is patient-specific rehearsal (PSR), in which the planned EVAR is rehearsed using the individual patient’s anatomy and the planned EVAR device. This exploratory study aims to explore PSR realism and its impact on procedural planning and operator preparedness for standard EVAR. Methods Standard EVAR procedures were scheduled for PSR. The aortic anatomy was segmented from each patient’s CT scan, and a virtual patient was uploaded into the simulator. The primary operator practised the PSR scenario immediately before the real EVAR case. Time spent creating the virtual patient and for the PSR scenarios was recorded. Operator preparedness was assessed with the cognitive appraisal ratio (CAR) before and after the PSR. Results Ten EVAR procedures were included during the study period. The median time to create the PSR scenarios was 24 (IQR:22–29) minutes. It was possible to complete 9 of the 10 PSR scenarios; one case could not be created due to poor imaging quality. Operators spent a median of 32 (IQR: 28–34) minutes to practice the case. 89% of the operators rated the simulations as realistic, and 89% reported that the PSR improved their confidence level, which was confirmed by a median reduction in CAR of 0.6 (IQR: 0.3–0.7) (p=.008). Conclusions PSR in EVAR is well received by the primary operator and has the potential to improve preparedness for real procedures. PSR in EVAR is feasible to implement in everyday clinical practice and in randomised controlled trials investigating peri- and postoperative outcomes.

Objectives:This study assessed the effectiveness of a modified simulation-based education (SBE) program, originally designed for vascular surgical trainees, adapted for endovascular scrub nurses (ESNs). The goal was to enhance their technical and non-technical skills and explore the program's impact on operating room (OR) teamwork and workflow. Materials and methods:A mixed-methods design was used. Eleven experienced ESNs-each with experience from approximately 100 endovascular procedures in the past 2-3 years-participated in role-reversal simulations, practicing peripheral endovascular procedures in the role of the surgeon under the guidance of a supervisor. Quantitative assessments included the Global Rating Scale (GRS) and an Examiner's Checklist for technical skills, while semi-structured interviews provided qualitative insights into non-technical domains such as teamwork, workflow, and job satisfaction. Results:The program significantly improved ESNs' technical skills, with GRS scores increasing from median [IQR] 19.0 [14.0; 24.0] to 43.0 [32.0; 44.0] (p=.004) and Examiner's Checklist scores rising from 49.0 [45.0; 58.0] to 73.0 [65.0; 78.0] (p=.004). Qualitative findings, derived from the themes of learning potential, job satisfaction, culture, feedback, overwhelming, and COVID-19, further demonstrated improvements in non-technical domains, including understanding of procedural sequences, teamwork, workflow, and job satisfaction. Participants reported better anticipation of surgeons' needs and a more collaborative atmosphere in the operating room. Conclusions:The role-reversal simulation-based education program for ESNs improved technical skills and strengthened teamwork and collaboration in the operating room. These findings highlight the potential of role-reversal training to enhance surgical performance and job satisfaction among OR staff.

Importance: Open surgical repair (OSR) should be prioritized for patients with asymptomatic abdominal aortic aneurysm (AAA) and long life expectancy, whereas endovascular repair (EVAR) is preferred for patients with suitable anatomy and life expectancy less than 2 to 3 years. However, life expectancy estimation and risk stratification are not well established. Objective: To evaluate risk-stratified survival differences between OSR and EVAR following elective AAA treatment. Design, Setting, and Participants: This cohort study used data from Danish national health registries. Patients older than 60 years undergoing elective AAA repair between 2004 and 2023 were categorized into 4 risk groups according to age, estimated glomerular filtration rate, and chronic obstructive pulmonary disease. Follow-up was until March 31, 2024. Exposure: OSR or EVAR for AAA. Main Outcomes and Measures: The primary outcome was overall survival. Secondary outcomes were incidence of AAA rupture and new cancer diagnosis. Comorbidities were balanced using inverse probability weighting. Kaplan-Meier estimators were generated for both treatments and the 4 risk score groups. Results: Of 6891 identified patients, 5757 (83.4%) were men. Women were older (median [IQR] age, 75.4 [70.9-79.3] vs 74.5 [70.5-78.5] years), more often had chronic obstructive pulmonary disease (156 women [13.6%] vs 512 men [8.9%]), and had lower estimated glomerular filtration rate (median [IQR], 68.4 [54.2-80.4] vs 70.4 [56.5-82.4] mL/min/1.73 m2) compared with men. The median follow-up was 8.28 years (95% CI, 8.10-8.50 years). OSR was associated with higher perioperative mortality in all risk groups. In low-risk patients, OSR was associated with a 10-month (95% CI, 2.2-18.3 months; P = .02) longer mean survival time restricted at 15 years compared with EVAR. In moderate-to-high-risk patients, OSR was associated with a 9-month (95% CI, 1.9-16.9 months; P = .008) shorter mean survival time restricted after 12.5 years compared with EVAR. No difference in mean survival time was seen in low-to-moderate-risk and high-risk patients at the study end. No differences in 10-year incidence of secondary AAA ruptures (OSR, 2.6% [95% CI, 1.9%-3.4%] vs EVAR, 2.2% [95% CI, 1.7%-2.7%]; P = .34) or solid malignant tumor (OSR, 18.6% [95% CI, 16.7%-20.5%] vs EVAR, 20.5% [95% CI, 18.9%-22.1%]; P = .35) were detected. Conclusions and Relevance: In this cohort study of 6891 patients with AAA, OSR was associated with higher perioperative mortality in all risk groups, but with longer mean survival only in low-risk patients. Conversely, EVAR was associated with longer mean survival in moderate-to-high-risk patients. These findings highlight the potential benefits of risk stratification when planning AAA treatment.

Introduction Among lower extremity artery disease (LEAD), symptomatic carotid stenosis (SCS) and abdominal aortic aneurysm (AAA), the disease burden is insufficiently illuminated from a patient and societal perspective. Such knowledge is central to identifying patients at risk of poorer outcomes. Therefore, the Danish Vascular (DanVasc) survey aims to describe self-reported health status, health literacy, medication adherence and loneliness, including changes over time, and investigate characteristics associated with worse self-reported health at baseline and their associations with poorer outcomes within 1 year (healthcare utilisation and mortality) in patients with LEAD, SCS and AAA.Methods and analysis The DanVasc survey, a national prospective cohort study combining survey data measured at several time points with register-based data, includes validated patient-reported outcome measures (PROMs) and ancillary questions developed with patient representatives. Our baseline survey (T0) follows the index contact in vascular outpatient clinics with follow-up surveys determined by the patient’s trajectory: (1) newly referred patients in conservative treatment trajectories; the date for the outpatient visit activates 1-month (T1), 3-month (T2) and 12-month (T3) follow-ups. (2) Patients referred for vascular surgery; the surgery date activates 1-month (T1), 3-month (T2) and 12-month (T3) follow-ups. The included PROMs assess health-related quality of life (HRQoL), anxiety and depression, sleep, frailty status, health literacy, medication adherence and loneliness. For LEAD, a disease-specific PROM evaluates HRQoL. For AAA, disease-specific ancillary questions are added. Additionally, the DanVasc survey includes questions on health behaviour, preventive measures and sexual life. The DanVasc survey will be linked to national registries to obtain socio-demographic information and data on redeemed prescriptions, clinical information, healthcare utilisation, comorbidities and mortality. From December 2023 to December 2024, we aim to recruit approximately 5500 patients from all seven DanVasc surgery departments. Patient characteristics will be reported using descriptive statistics. Changes over time and factors associated with poorer health outcomes will be analysed using linear, logistic and Cox proportional hazard models, presented as univariate and multivariate regressions.Ethics and dissemination Approval for the collection of medical record data was granted by the Central Denmark Region, acting on behalf of all Danish regions (record 1-45-70-94-22). Consent to participate is obtained prior to answering the survey. Results will be disseminated through peer-reviewed scientific publications and conference presentations, and findings will be shared with patients and relevant stakeholders via public and social media.

Objectives: Abdominal aortic aneurysm (AAA) diameter is the primary predictor of AAA rupture. However, smaller aneurysms do rupture, and other parameters are required for a more nuanced risk stratification. Reduced renal function is associated with increased cardiovascular risk and thrombosis, but the impact of renal function on ILT and AAA size remains unknown. This study aimed to investigate the association between creatinine level and volume of ILT and AAA. Methods: In a cross-sectional study, 184 patients with AAA under ultrasound surveillance were included. ILT volume and thickness, and AAA volume and diameter, were measured using three-dimensional contrast-enhanced ultrasound. ILT and AAA measures were compared with creatinine levels. Results: No associations were found between creatinine level and ILT or AAA volume (p = 0.18 and p = 0.41). There were no differences in ILT volume between patients with normal and elevated creatinine levels, when adjusting for AAA size and comorbidities (p = 0.06 and p = 0.54). A positive association was found between ILT volume and AAA volume (p < 0.001). Creatinine level did not influence this association (p = 0.06). Conclusions: In this study, creatinine level did not seem associated with ILT or AAA volume. Longitudinal studies are required to elucidate associations between renal function, clinical outcomes, and ILT and AAA development.

Acute limb ischaemia is a vascular emergency with very high morbidity and mortality. It is defined by abrupt reduction in arterial perfusion and symptom duration of less than 14 days. The clinical presentations varies, but the six P's: pain, pallor, pulseless, paraesthesia, paralysis and perishingly cold, are present to some degree. Quick and efficient assessment is necessary, but amputation risk is high. Treatment options include catheter-directed thrombolysis, endovascular revascularization and open surgery. Endovascular treatment should be considered in patients with higher perioperative risk, as argued in this review.

OBJECTIVE:This nationwide, retrospective, registry study aimed to evaluate the rate of continued opioid use after revascularisation in patients with lower extremity peripheral artery disease (PAD) and the association between opioid treatment and post-discharge mortality. METHODS:Using Danish national registries, all patients undergoing first time endovascular or surgical revascularisation for PAD (1996 - 2018) were identified. Patients were categorised based on opioid use before admission: current new users (first time opioid prescription within 30 days before admission); current long term users (opioid prescription both before and within 30 days before admission); recent users (prescription within 31 - 365 days before admission); former users (prescription more than one year before); and non-users (no history of opioid prescription). Outcomes post-discharge were analysed using multivariable Cox regression. RESULTS:Among 40 186 patients (median age 70 years, 54% men) surviving revascularisation, 5.4% were current new users, 22.9% current long term users, 14.5% recent users, 19.0% former users, and 38.2% non-users. A higher proportion of opioid users presented with chronic limb threatening ischaemia. Within three months post-discharge, opioid prescription refills were highest among current long term users (76.7%) and lowest among non-users (14.6%). Compared with non-users, the one year adjusted hazard ratio for all cause mortality was 1.64 (95% confidence interval [CI] 1.44 - 1.86) for current new users, 1.59 (95% CI 1.46 - 1.74) for current long term users, and 1.13 (95% CI 1.03 - 1.26) for recent users, with no increased risk for former users. CONCLUSION:This nationwide study identified a high risk subgroup of PAD patients with substantial opioid use and elevated mortality risk. Despite revascularisation, many with prior opioid use continued treatment post-discharge, highlighting the need for cautious prescribing and structured follow up to manage persistent pain and complex care needs. Although causality cannot be confirmed, pre-revascularisation opioid use was associated with a higher all cause mortality rate, probably reflecting greater disease severity.

Background: Abdominal aortic aneurysms (AAAs) are an important cause of death. Small AAAs are surveyed with ultrasound (US) until a defined diameter threshold, often triggering a computer tomography scan and surgical repair. Nevertheless, 5%-10% of AAA ruptures are below threshold, and some large AAAs never rupture. AAA wall biomechanics may reveal vessel wall degradation with potential for patient-centred risk assessment. This clinical study investigated AAA vessel wall biomechanics and deformation patterns, including reproducibility. Methods: In 50 patients with AAA, 183 video clips were recorded by two sonographers. Prototype software extracted AAA vessel wall principal strain characteristics and patterns. Functional principal component analysis (FPCA) derived strain pattern statistics. Results: Strain patterns demonstrated reduced AAA wall strains close to the spine. The strain pattern "topography" (i.e., curve phases or "peaks" and "valleys") had a 3.9 times lower variance than simple numeric assessment of strain amplitudes, which allowed for clustering in two groups with FPCA. A high mean reproducibility of these clusters of 87.6% was found. Median pulse pressure-normalised mean principal strain (PPPS) was 0.038%/mm Hg (interquartile range: 0.029-0.051%/mm Hg) with no correlation to AAA size (Spearman's rho = 0.02, false discovery rate-p= 0.15). Inter-operator reproducibility of PPPS was poor (limits of agreement: +/- 0.031%/mm Hg). Discussion: Strain patterns challenge previous numeric stiffness measures based on anterior-posterior-diameter and are reproducible for clustering. This study's PPPS aligned with prior findings, although clinical reproducibility was poor. In contrast, US-based strain patterns hold promising potential to enhance AAA risk assessment beyond traditional diameter-based metrics.

The heterogeneity of atherosclerotic plaques is critical for their vulnerability to rupture and the associate risk of cardiovascular events. Most proteomic studies have only examined bulk changes, potentially obscuring key spatial differences in protein content and abundance. Here we report a high-resolution spatial proteomics workflow that allows exploration of the molecular landscape of human plaques and murine myocardial tissue. This combines laser capture microdissection of tissue areas (50,000 µm² from 10 µm-thick sections, corresponding to < 30 cells), with high-sensitivity ion-mobility mass spectrometry, allowing spatial profiling of cellular and extracellular matrix (ECM) proteomes. Over 2700 proteins were detected, revealing substantial intra-plaque proteome heterogeneity across distinct regions (lipid-rich, media layers, shoulder regions, necrotic core, intima) and distance from the lumen into the artery wall. Strong inverse correlations were detected between proteases (e.g. cathepsin-B) and core structural ECM components (e.g. perlecan, HSPG2) consistent with active ECM remodeling. Analysis of media layers indicated distinct protein signatures associated with smooth muscle contraction and cell-cell communication. Blood coagulation signatures, including platelet degranulation and fibrin clot formation were enriched at the intimal surface. Inflammatory markers (clusters of differentiation 4 and 68, CD4/CD68; vascular cell adhesion molecular 1, VCAM1) and vascular damage markers (tenascin-C, TNC) were enriched in shoulder regions. The necrotic core was dominated by blood proteins, consistent with intra-plaque hemorrhage. The capacity of this workflow to resolve changes over modest distances (225 µm) provides unprecedented insights into the spatial organisation of the atherosclerotic microenvironment, offering a powerful tool for elucidating plaque biology and identifying potential therapeutic targets. ### Competing Interest Statement The authors have declared no competing interest. * ALDH1A1 : aldehyde dehydrogenase 1 family member A1 ALDH2 : aldehyde dehydrogenase 2 BCAM : basal cell adhesion molecule BGN : biglycan C3 : Complement protein 3 C4A/B : complement proteins 4 A and B isoforms CAA : 2-chloroacetamide CD4 : cluster of differentiation 4 CD36 : cluster of differentiation 36 CD68 : cluster of differentiation 68 CNN1 : calponin 1 COL6A1 : COL6A2, COL6A3, collagen VI-alpha1, -alpha2 and -alpha3 chains respectively CTSB : cathepsin B CVD : cardiovascular disease DDA : data dependent acquisition DDA-PASEF : data dependent acquisition with parallel acquisition-serial fragmentation DIA : data independent acquisition DIA-PASEF : data independent acquisition with parallel acquisition-serial fragmentation DDM : N -dodecyl-β-D-maltoside ECM : extracellular matrix FFPE : formalin-fixed paraffin-embedded FGA, FGB, FGG : fibrinogen alpha-, beta- and gamma- chains respectively FLNA : filamin A FTL : ferritin light chain GCFHR : GTP cyclohydrolase 1 feedback regulatory protein GO : gene ontology GSEA : gene set enrichment analysis HP : haptoglobin HSPG2 : heparin sulfate proteoglycan 2/perlecan IGHM : immunoglobulin heavy constant mu LAMB2 : laminin beta-2 chain LAMC1 : laminin gamma-1 chain LCM : laser-capture microdissection LC-MS/MS : liquid chromatography-mass spectrometry LDL : low-density lipoproteins LUM : lumican MARCO : macrophage receptor with collagenous structure MMP12 : matrix metalloproteinase 12 MYL6, MYL9 : myosin light chains 6 and 9 respectively MYH10, MYH11 : myosin heavy chains 10 and 11 respectively PASEF : parallel acquisition-serial fragmentation PBS : phosphate-buffered saline PCA : principal component analysis POSTN : periostin PRDX3 : peroxiredoxin 3 PSMs : peptide spectral matches TCEP : tris(2-carboxyethyl)phosphine TEAB : tetraethyl ammonium bicarbonate TFA : trifluoroacetic acid TimsTOF : total ion mobility-time of flight TNC : Tenascin C VCAM1 : vascular cell adhesion molecule 1 VCAN : versican VWF : von Willebrand factor. Novo Nordisk Foundation, https://ror.org/04txyc737, NNF13OC0004294, NNF20SA0064214 Lundbeck Foundation, https://ror.org/03hz8wd80, R322-2019-2337

Objective: Ultrasound-based aortic stiffness estimation has the potential to improve the diagnosis and prognosis of patients with abdominal aortic aneurysms (AAA), as a complement to routinely used diameter surveillance. However, existing methods have shown limited reproducibility, possibly influenced by the unknown effects of the highly variable ultrasound probe pressure. This proof-of-concept study addressed this gap by analyzing time-resolved ultrasound sequences from AAA patients. Methods: Two-dimensional ultrasound sequences were acquired from 10 AAA patients, applying light and firm probe pressure. Diameter variations and stiffness were evaluated and compared. An in-silico simulation was performed to support the in-vivo observations. Results: Measured stiffness decreased with an increased probe pressure. Specifically, in the most responsive patient group, the cyclic diameter variation between diastole and systole changed from 1% at light probe pressure to 5% at firm probe pressure, and the estimated stiffness decreased by a factor of 6.3. Another group of patients showed a marginal increase in the diameter variations and a smaller decrease in stiffness (factor of 1.5) when transitioning from light to firm probe pressure. These two behaviors were reproduced via numerical simulations, showing that the different responses to probe pressure depend on the stress-strain relationship of the wall material. Conclusion: Varying the ultrasound probe pressure can alter the in-vivo mechanics of AAAs. Significance: This proof-of-concept study suggests potential implications for AAA mechanical characterization via ultrasound imaging.

Atherosclerotic plaque rupture is a major cause of cardiovascular events. Plaque destabilization is associated with extracellular matrix (ECM) modification involving proteases which generate protein fragments with new N-termini. We hypothesized that rupture-prone plaques would contain elevated fragment levels, and their sequences would allow identification of active proteases and target proteins. Plaques from 21 patients who underwent surgery for symptomatic carotid artery stenosis were examined in an observational/cross-sectional study. Plaques were analyzed by liquid chromatography-mass spectrometry for the presence of N-terminal fragments. 33920 peptides were identified, with 17814 being N-terminal species. 5735 distinct N-terminal peptides were quantified and subjected to multidimensional scaling analysis and consensus clustering. These analyses indicated three clusters, which correlate with gross macroscopic plaque morphology (soft/mixed/hard), ultrasound classification (echolucent/echogenic), and the presence of hemorrhage/ulceration. Differences in the fragment complements are consistent with plaque-type-dependent turnover and degradation pathways. Identified peptides include signal and pro-peptides from synthesis and those from protein fragmentation. Sequence analysis indicates that targeted proteins include ECM species and responsible proteases (meprins, cathepsins, matrix metalloproteinases, elastase, and kallikreins). This study provides a large data set of peptide fragments and proteases present in plaques of differing stability. These species may have potential as biomarkers for improved atherosclerosis risk profiling.

Objective: Endovascular aortic repair (EVAR) is being used increasingly for the treatment of infrarenal abdominal aortic aneurysms. Improvement in educational strategies is required to teach future vascular surgeons EVAR skills, but a comprehensive, pre-defined e-learning and simulation curriculum remains to be developed and tested. EndoVascular Aortic Repair Assessment of Technical Expertise (EVARATE), an assessment tool for simulation based education (SBE) in EVAR, has previously been designed to assess EVAR skills, and a pass limit defining mastery level has been set. However, EVARATE was developed for anonymous video ratings in a research setting, and its feasibility for real time ratings in a standardised SBE programme in EVAR is unproven. This study aimed to test the effect of a newly developed simulation based modular course in EVAR. In addition, the applicability of EVARATE for real time performance assessments was investigated. Methods: The European Society of Vascular Surgery (ESVS) and Copenhagen Certification Programme in EVAR (ENHANCE-EVAR) was tested in a prospective cohort study. ENHANCE-EVAR is a modular SBE programme in EVAR consisting of e-learning and hands-on SBE. Participants were rated with the EVARATE tool by experienced EVAR surgeons. Results: Twenty-four physicians completed the study. The mean improvement in EVARATE score during the course was +11.8 (95% confidence interval 9.8 - 13.7) points (p < .001). Twenty-two participants (92%) passed with a mean number of 2.8 +/- 0.7 test attempts to reach the pass limit. Cronbach's alpha coefficient was 0.91, corresponding to excellent reliability of the EVARATE scale. Differences between instructors' EVARATE ratings were insignificant (p = .16), with a maximum variation between instructors of +/- 1.3 points. Conclusion: ENHANCE-EVAR, a comprehensive certifying EVAR course, was proven to be effective. EndoVascular Aortic Repair Assessment of Technical Expertise (EVARATE) is a trustworthy tool for assessing performance within an authentic educational setting, enabling real time feedback.

Background: The current management of abdominal aortic aneurysm (AAA) hinges upon assessing diameter using ultrasound (US). Diameter reproducibility with conventional two-dimensional ultrasound (2D-US) is challenging and requires experienced operators. A novel automatic three-dimensional ultrasound (3D-US) system enables on-cart software-assisted diameter estimation (3D-SAUS), potentially facilitating more precise diameter measurements than 2D-US. This study aimed to assess the variance of AAA diameter measurements among US novices and experts by comparing 2D-US with 3D-SAUS in a clinical setting. Methods: A total of 580 US scans were scheduled by 29 US operators (13 experts and 16 novices) on 10 patients with AAAs. Experts and novices measured all patients' AAA anterior-posterior (AP) diameters with 2D-US and 3D-SAUS. Outcomes were limits of agreement (LoA) using a mixed-effects model. Results: In total, 564 of 580 planned US scans were performed. 500 US scans were automatically analyzed by the software and included. When using 3D-SAUS instead of 2D-US, novices reduced their LoA from +16.5% to +10.2% (P<0.001), reaching the experts'LoA of +10.5% (P=0.782 for difference). The experts'LoA was +10.5% for 2D-US and +9.7% for 3D-SAUS, with no statistically significant difference between the two modalities (P=0.423). Conclusions: Clinical implementation of the 3D-SAUS demonstrates a substantial reduction in variance in AAA diameter measurements among novice sonographers, surpassing the performance of conventional 2D-US techniques. Additionally, using the 3D-SAUS tool enables novice sonographers to achieve proficiency levels comparable to those of experts employing conventional 2D-US.