Background: Vulnerable carotid atherosclerotic plaques are prone to cap rupture and thrombosis, yet definitive assessment still relies on postoperative histology. We investigated whether circulating circular RNAs (circRNAs) in peripheral blood mononuclear cells (PBMCs) can identify plaque vulnerability preoperatively. Method: In patients undergoing carotid endarterectomy, plaques were classified as vulnerable or stable, and PBMC expression of candidate circRNAs (circVIRMA, circGRN, circANRIL and CDR1as) and paired linear transcripts was quantified by RT-qPCR. A composite in-plaque_SCORE (IL-1β, IL-6, IL-10, PPARγ mRNAs) characterized intraplaque inflammation. We derived two PBMC metrics: circRNA_SCORE (mean expression of deregulated circRNAs) and circ/linear mRNA_SCORE (mean of circ/linear mRNA expression ratios) and evaluated diagnostic performance by Receiver Operating Characteristic curve (ROC) analysis and logistic regression. Results: circVIRMA and circGRN were modestly increased in PBMCs from patients with vulnerable plaques, whereas linear host genes were unchanged. CDR1as was markedly upregulated and showed the strongest discrimination among the other circRNAs, similarly to the circRNA_and circRNA/linear mRNA ratio_SCOREs. Indeed, circRNA_SCORE correlated positively with the intraplaque inflammatory in-plaque_SCORE, linking systemic signatures to local plaque biology. In plaque tissue, CDR1 mRNA was reduced while CDR1as was relatively preserved, yielding a higher CDR1as/CDR1 mRNA ratio in vulnerable lesions. Conclusions: PBMC circRNAs—particularly CDR1as—show promise as noninvasive biomarkers of carotid plaque vulnerability and reflect plaque inflammatory status. Validation in independent cohorts and integration with imaging could enable improved preoperative risk stratification.

Thoracic endovascular aortic repair (TEVAR) is one of the main treatments, together with open aortic repair, for thoracic aortic aneurysm. This procedure is associated with low procedural morbidity and mortality and provides satisfactory mid-term results. However, identifying the optimal location for device deployment before the operation remains essential. In previous studies, computer simulations were used to examine the hemodynamic stress linked to different areas of the arch, pinpointing regions unsuitable for TEVAR delivery. Computational fluid dynamics (CFD) simulations suggest that zone 3 poses the most challenges for delivering endograft in type III arches, as it is considered a hostile region from biomechanical and hemodynamic perspectives. Morphologically, type III aortic arch shows a more pronounced curvature and a lower position of the arch, resulting in increased separation between the ascending and descending aorta. However, these studies utilized 3D geometrical models reconstructed from computed tomography angiography scans. Still, the flow boundary conditions were based on existing data rather than the specific hemodynamic characteristics of the patient. To bridge this gap, the present study uses MRI flow wave data to compute displacement forces (DFs) for each proximal landing zone. We found that zones 0 and 3 exhibited a high magnitude of displacement forces. Still, only zone 3 was identified as the most hemodynamically stressed area when the force was normalized for the lumen area. Furthermore, there was a significant discontinuity in the upward components of DFs between zone 2 and zone 3. The patient-specific assessment of displacement forces enabled us to identify suboptimal areas for TEVAR delivery, suggesting that personalized computer simulations could greatly enhance preoperative planning for TEVAR procedures.

Background/Objectives: To describe our experience of using an alternative technique for retrograde branch graft cannulation during Branched EndoVascular Aortic Repair (B-EVAR) of complex abdominal and thoraco-abdominal aortic aneurysm (TAAA) with branched endografts. Methods: Data from patients who underwent B-EVAR for TAAA/complex abdominal aneurysms and in whom the cannulation of a branch was performed through a retrograde approach with our technique were retrospectively collected and analyzed. The technique consists of the placement of two 4F Ber catheters in both femoral arteries, which are advanced in parallel with the main graft before its deployment and left in the aneurysmal sac. These catheters are then used as a bailout for the retrograde cannulation of one or more branches of the endograft. Results: The technique was employed in 4 patients (1 female, 1 urgent) treated from 2018 onward, allowing the successful catheterization of 4 challenging branches that could not be catheterized using other approaches. The patients' mean age was 80.7 + 2.2 years. No intraoperative nor postoperative complications linked to the technique occurred. Conclusions: The placement of two catheters from both femoral arteries inside the aneurysmal sac before graft deployment can be safe and useful for bailout retrograde cannulation of any branch of the endograft, when other techniques fail.

BACKGROUND: In-stent restenosis (ISR) is a well-recognized late complication of carotid artery stenting (CAS), but there is no consensus on the optimal endovascular treatment. The aim of this study was to compare the short- and mid-term outcomes of paclitaxel-eluting drug-coated balloon (DEB) and cutting balloon (CB) angioplasty for the treatment of significant carotid ISR. METHODS: Consecutive patients treated for significant (>70%) ISR after CAS at a single tertiary center between January 2022 and June 2023 with either a paclitaxel-coated DEB (ELUTAX (TM)) or a CB (WOLVERINE (TM)) were retrospectively analyzed. Allocation between the two devices was performed at the operator's discretion in a non-randomized fashion. The primary safety endpoint was the composite of any neurological event, death, and recurrent restenosis >50% at 30 days. The primary efficacy endpoint was freedom from recurrent >70% restenosis at 12 months on duplex ultrasound surveillance. Categorical variables were compared with the Chi-square or Fisher's Exact Test, continuous variables with Student's t-test. Freedom from restenosis was estimated by the Kaplan-Meier method and compared with the log-rank test. Statistical significance was set at P<0.05. RESULTS: Thirty patients were included (18 DEB, 12 CB). Baseline demographic and anatomical features were comparable between groups, with the exception of a higher prevalence of chronic obstructive pulmonary disease in the DEB group (38.9% vs. 0%, P=0.02). Procedural technical success was achieved in all 30 cases. At 30 days, no neurological events, deaths or recurrent restenoses >50% were observed in either group. After a mean follow-up of 14.1 +/- 8.1 months, freedom from >70% restenosis at 12 months was 100% in the DEB group and 41.7 +/- 14.2% in the CB group (log-rank P=0.02). CONCLUSIONS: In this small single-center retrospective experience, both DEB and CB angioplasty proved feasible and safe for the endovascular treatment of carotid ISR after CAS. DEB angioplasty was associated with a significantly lower rate of recurrent restenosis at 12-month follow-up. These hypothesis-generating findings should be confirmed in larger, ideally prospective and randomized studies before any definitive recommendation can be made.

BACKGROUND:To analyze the impact of sex on the occurrence of death, stroke, and myocardial infarction at 30 days and at 1 year after either carotid endarterectomy (CEA) or carotid artery stenting (CAS) for the treatment of significant carotid stenosis on the real-world dataset coming from TriNetX. METHODS:A retrospective multicenter cohort study was built within the TriNetX platform (TriNetX LLC, Cambridge, MA) to investigate cohorts of patients aged 18 years or older diagnosed with carotid artery occlusion or stenosis receiving either CEA or CAS from January 1, 2010 to June 19, 2025. Patients were also classified as symptomatic, thus delineating 4 cohorts: symptomatic CAS, symptomatic CEA, asymptomatic CAS, and asymptomatic CEA. The primary outcome was identified as the occurrence of death from all causes, stroke and myocardial infarction, within each of the 4 cohorts of patients, comparing male versus female patients. These outcomes were evaluated both individually and as a composite outcome within 1 month and 1 year after the intervention. RESULTS:The results of 59,340 procedures of carotid revascularization (5599 CAS and 53,741 CEA) from 2010 ongoing were analyzed, being 22,574 on female patients (38.0%). At 30 days, the propensity-matched score analysis adjusted for age did not show any significant difference for the risk of all the outcomes between males and females both in the cohort of patients who underwent CEA as well as in that of patients who underwent CAS, neither in symptomatic nor in asymptomatic patients. At 1 year, no significant differences were recorded between men and women for the all the outcomes in both the cohorts, except for a lower survival of symptomatic female patients who underwent CAS (86.7% vs. 93.8%, P = 0.013). CONCLUSION:At 30 days and at long-term follow-up, no differences were recorded between male and female patients undergoing CAS or CEA, except for a lower 1-year survival of symptomatic female patients who underwent CAS.

Background: To characterize the variation of the renal arteries' origin from the aorta, through examination of computed tomography angiographies (CTAs) in a cohort of patients, and to evaluate any gender-related difference. Methods: CTA of the thoracoabdominal district in patients with a nondilated aorta (group A), patients with aortic aneurysm involving the origin of splanchnic and/or renal vessels (group B), and patients with abdominal aortic aneurysm (group C), were retrospectively analyzed. The diameter and angles of emergence (axial and craniocaudal) of the renal arteries were measured, as well as their mutual distance, and the distance between the renal vessels and the superior mesenteric artery/the aortic bifurcation. Shapiro-Wilk, one-way analysis of variance and bivariate Pearson's Correlation tests were performed as appropriate. A P value <0.05 was considered statistically significant. Results: Six-hundred CTA of patients (452 males) were examined, being 286 in group A, 119 in group B, and 195 in group C. When examining the whole population and also the subgroup of female patients, the clock position of the right renal artery (RRA) was the only parameter that followed a Gaussian distribution, and its ostium raised from the aorta with a mean axial angle of -61.5 degrees +/- 16.6 degrees. There was a negative correlation between left renal artery (LRA) and RRA's coronal angle and aortic diameter at the same level, as well as between the LRA's clock position and the aortic diameter at the same level. The longitudinal distances between established landmarks and both renal arteries positively correlated to the aortic diameter. Conclusions: The LRA showed a high anatomic variability, both in males and in females. With the increase of the aortic diameters in the juxtarenal/infrarenal portion of the aorta, the renal vessels tended to have a more horizontal course in the coronal view, a more acute "clock-position"and longer longitudinal distances between their ostia and the aortic bifurcation.

Background/Objectives: Carotid artery stenosis (CAS) is one of the main causes of stroke, and the vulnerability of plaque has been proved to be a determinant. A joint analysis of shear wave elastography, a radiofrequency echo-based wall tracking technique for arterial stiffness evaluation, and of autonomic and baroreflex function is proposed to noninvasively, preoperatively assess plaque vulnerability in asymptomatic CAS patients scheduled for carotid endarterectomy. Methods: Elastographic markers of arterial stiffness were derived preoperatively in 78 CAS patients (age: 74.2 + 7.7 years, 27 females). Autonomic and baroreflex markers were also assessed by means of an analysis of the beat-to-beat fluctuations in heart period and systolic arterial pressure, derived at rest in supine position (REST) and during active standing. Postoperative analysis identified 36 patients with vulnerable plaque (VULN) and 42 with stable plaque (STABLE). Results: Baroreflex sensitivity (BRS) at a respiratory rate decreased during STAND only in VULN patients, being much higher at REST compared to STABLE levels. Autonomic indexes were not helpful in separating experimental conditions and/or populations. The Young’s modulus (YM) of the plaque was lower in the VULN group than in the STABLE one. Cardiovascular control and elastographic markers were significantly correlated only in VULN patients. A multivariate logistic regression model built combining YM and BRS at the respiratory rate improved the prediction of plaque vulnerability, reporting an area under the ROC curve of 0.694. Conclusions: Noninvasive techniques assessing shear wave elastography and baroreflex control could contribute to the early detection of plaque vulnerability in patients with asymptomatic CAS.

PURPOSE:The study aim is to assess how surgical or endovascular treatments can impact carotid perivascular inflammation in patients affected by severe carotid artery stenosis. METHODS:Seventy consecutive patients with unilateral carotid stenosis from the BAROX trial were included in this study. CT angiography (CTA) exams were conducted on a dual-source CT system before and after the carotid endarterectomy (CEA) or stenting. Perivascular adipose tissue (PVAT) CT attenuation measurement in a 40 mm proximal segment of the internal carotid artery was measured as carotid PVAT (CPVAT). CT attenuation was calculated as the mean attenuation of all voxels in the range of -30 to -190 HU, thresholds used for identifying adipose tissue. RESULTS:The median CPVAT measurements before and after both surgical and percutaneous procedures in the stenotic side was -60 (-66, -57) before and -61 (-66, -56) after procedure (p = 0.046). The median CPVAT measurements before and after the surgical procedures was -59 (-66, -57) before and -59 (-62, -54) after procedure (p = 0.006). As well as before- and after stent placement was -60 (-65, -55) before and -65 (-70, -60) after procedure (p = 0.103). A correlation analysis showed a positive correlation between post-procedure CPVAT and the occurrence of the procedure (ρ = 0.403, p = 0.003), as well as a positive correlation between pre- and post-procedure CPVAT on the untreated side and the degree of stenosis (pre-procedure: ρ = 0.328, p = 0.007; post-procedure: ρ = 0.271, p = 0.027). CONCLUSION:We found an increase in CPVAT following CEA, indicating that an inflammatory process occurs during treatment.

The assessment of carotid plaque vulnerability is a relevant clinical information that can help prevent adverse cerebrovascular events. To this aim, in this work we study the ability of different non-invasive methods for assessing plaque vulnerability in patients undergoing carotid endarterectomy (CEA). Histological examinations of patients’ plaque samples were conducted after CEA while ultrasound (US) and computed tomography angiography (CTA) acquisitions were performed preoperatively. US acquisition included point shear wave elastography (p-SWE) and a radio frequency echo-based wall tracking mode for the evaluation of arterial wall stiffness. CTA images were segmented, and the results were used for an ad hoc procedure that semi-automatically reconstructed the atherosclerotic wall providing a 3D model of the different plaque components to perform patient-specific finite element analysis (FEA) of stress distributions. One hundred patients were involved in the study and a macroscopic assessment of the surgeon was used to classify carotid atherosclerotic plaques as vulnerable or stable. The data derived from histological analysis, US acquisitions and FEA were correlated with the outcome of the classification. Indeed, histological features differentiated between vulnerable and stable plaques, confirming the surgeon’s classification. From p-SWE, the measurement of Young’s Modulus (YM) in stable plaques was significantly higher than in vulnerable plaques. Also stress indexes related to the Von Mises and Max Principal stresses from FEAs showed statistically significant differences between plaque groups. These results demonstrate that both stiffness-related US measurements and stress parameters derived preoperatively from computational analyses were able to differentiate patients with vulnerable plaques from ones with stable plaques. Thus, the development and application of new methods for a non-invasive biomechanical assessment of atherosclerotic artery walls could give valuable information for plaque vulnerability evaluation.

BACKGROUND:Optimal management of uncomplicated type B aortic dissection (uTBAD) remains debated. While thoracic endovascular aortic repair (TEVAR) promotes false lumen thrombosis (FLT) and remodeling, the early clinical profile and long-term benefits in routine practice need further investigation. The pre-trial setup of the European Uncomplicated Type B Aortic Repair (EU-TBAR) program prospectively collated multicenter outcomes to evaluate real-world clinical outcomes of TEVAR for uTBAD across European centers, and to identify independent predictors of mortality, reintervention, and aortic remodeling to inform the design of a definitive randomized EU-TBAR trial. METHODS:Multicenter observational cohort of consecutive patients undergoing TEVAR for uTBAD and related descending thoracic pathology across European centers. Standardized electronic case-report forms captured demographics, presentation, imaging, procedural details, and outcomes. Primary outcomes were in-hospital and follow-up mortality; secondary outcomes included complications, reintervention, and aortic remodeling. Multivariable logistic regression identified predictors of mortality, reintervention, and remodeling. RESULTS:We analyzed 263 patients (mean age 61.4 ± 13.4 years; 79.5% male) from six countries. In-hospital mortality was 9.9%, and mortality during follow-up was 14.1% (median follow-up time ≈ 1 year). Postoperative acute kidney injury (AKI) was the strongest independent predictor of death (odds ratio [OR] 9.93, P < 0.0001); additional predictors included AKI at presentation (OR 4.24, P = 0.012), syncope (OR 3.15, P < 0.0001), and ventilation for >48 hr (OR 2.69, P = 0.024). Higher hemoglobin (OR 0.74 per g/dL, P < 0.0001) and estimated glomerular filtration rate (OR 0.79 per 10 units, P < 0.0001) were protective; reintervention was associated with lower mortality (OR 0.26, P = 0.013). Reintervention occurred in 18.3% at a median of 168 days; discharge endoleak (present in 18.3%) tripled reintervention odds (OR 3.08, P = 0.003). Imaging at discharge and follow-up was performed in 70.7% and 63.9%, respectively. At follow-up, FLT was complete in 42.1% and partial in 39.3%. Remodeling was associated with beta-blockers (descending aorta OR 3.58, P = 0.009), prior thoracic surgery (suprarenal OR 5.47; infrarenal OR 8.33; both P = 0.008), and targeted branch stenting (e.g., celiac OR 31.0, P = 0.016). Female sex independently predicted FLT (OR 11.53, P = 0.022). Survival was lower for emergent cases (65% vs 79-78%; P = 0.039) and in patients with postoperative AKI (36% vs. 86%; P < 0.001). CONCLUSION:This pre-trial setup and analysis successfully confirm the feasibility and methodological foundation for the definitive EU-TBAR trial. There is a clinical equipoise across European centers, with significant practice variation justifying a randomized trial comparing pre-emptive TEVAR versus medical management for uTBAD. Key mortality predictors provide objective criteria for patient selection, while the reintervention rate establishes important trial endpoints.

OBJECTIVE:This study seeks to assess the influence of using patient-specific data from different imaging methods on evaluating carotid plaque vulnerability via finite element analysis (FEA) instead of using data derived from the literature. METHODS:54 patients were considered in this analysis, who preoperatively underwent computed tomography angiography (CTA) and ultrasound (US) imaging evaluations. The composition (i.e. calcific, lipidic and mixed) and vulnerability (i.e. stable or vulnerable) of their plaques were evaluated by macroscopic and histologic assessment post-endarterectomy. In particular, the plaques of these 54 patients were classified as mixed. 3D reconstructions of the carotid artery were generated from CTA scans, and computational analyses were performed using two different simulation settings for material properties and loads: a) the material properties of the plaque components were set as an average of values available in the literature (LIT-based); b) the material property of the plaque fibrous content was modified using stiffness data derived from US shear-wave elastography imaging (SWE-based). Statistical analyses were conducted to compare stress parameters obtained from the different simulations within groups of vulnerable and stable plaques. RESULTS:Comparisons between LIT-based and SWE-based FEA revealed notable differences in stress parameters associated with plaque vulnerability. In particular, the stress values derived from SWE-based simulations provided distinct stratification of vulnerable versus stable plaques, whereas LIT-based models showed limited differentiation. Significant variations in von Mises (p = 0.015, p = 0.037) and maximum principal stress (p = 0.014) distributions were observed in SWE-based FEA. CONCLUSIONS:Patient-specific modelling and computational analysis integrating CTA-derived morphological with US-derived biomechanical data could improve the assessment of plaque vulnerability in mixed-composition carotid plaques.

Biomechanical analysis of crosstalk between the carotids remains poorly underexplored. This study aims to clarify the impact of severe carotid stenosis on the local hemodynamics of the opposite carotid artery, before and after treatment. Data from patients diagnosed with severe internal carotid artery stenosis (≥ 70%), treated with carotid artery stenting (CAS) or carotid endarterectomy (CEA) were analyzed. Both sides' anatomical and hemodynamic remodeling parameters were evaluated before and after treatment. Forty-two patients underwent computed tomography angiography (CTA) and phase-contrast magnetic resonance imaging (PC-MRI) to measure carotid diameters and flow rates in the common, internal, and external carotids (CCA, ICA, and ECA, respectively) before and after CAS or CEA. Additionally, patient-specific computational fluid dynamics (CFD) simulations were performed to calculate time-averaged wall shear stress (taWSS) before and after the treatment. Post-treatment analysis revealed anatomical and hemodynamic changes in the contralateral side. Specifically, there was a decrease in blood flow and an increase in vessel diameters, particularly in the CCA, of patients who had undergone CEA (pre vs. post: flow p = .029, diameter p = .007). Additionally, there was an increase in low taWSS areas in the SOI after the operation: CEA from 15.50 (10.80) % to 18.00 (20.25) %, CAS from 17.00 (15.55) % to 19.50 (20.50) %. The study revealed new anatomical and hemodynamic parameters changes in both carotids, offering insights into the interaction between stenotic and contralateral carotid arteries in post-operative conditions.

Background:Despite screening recommendations, many abdominal aortic aneurysms (AAAs) are incidentally imaged during various imaging studies but are frequently missed, especially when the imaging procedure is not specifically targeted to the aorta. The aims of this study were to conduct a retrospective analysis to assess the incidence of AAAs as incidental findings on lumbar spine magnetic resonance imaging (MRI) and to evaluate the detection rate of these findings reported by radiologists. Methods:After ethics committee approval, this retrospective study included patients aged 55 years or older who underwent for any indication a lumbar spine 1.5-T MRI between January 2017 and June 2023 at the Unit of Radiology of the IRCCS (Research Hospital) Policlinico San Donato. Patients with a known history of AAA or prior AAA repair were excluded. The maximal aortic diameter of the abdominal aorta was measured on axial and sagittal T2-weighted images. A threshold of ≥30 mm was adopted to define the presence of an AAA. The Mann-Whitney U test was used to compare measurements between sexes and reporting status (reported or not reported). Bland-Altman analysis evaluated agreement between axial and sagittal measurements. Spearman's correlation assessed relationships between age, AAA detection, and measurement values. Results:Out of 1,922 patients, 84 [4.4%, 95% confidence interval (CI): 3.5-5.3%] had an abdominal aorta diameter ≥30 mm, qualifying as AAAs. Only 26 (31.0%, 95% CI: 21.1-40.8%) of these AAAs were reported by radiologists. A significant difference in detection rates between sexes was observed (P<0.001), with males showing higher prevalence (8.4%, 95% CI: 6.4-10.3%) compared to females (1.7%, 95% CI: 0.9-2.4%). A significant difference was found also between the median maximal aortic diameter of 38 mm [interquartile range (IQR), 33-43 mm] for reported AAAs and 32 mm (IQR, 30-35 mm) for not reported AAAs (P=0.003). Bland-Altman analysis demonstrated good agreement between axial and sagittal measurements, showing also a strong correlation (ρ=0.93, P<0.001). Age correlated with the highest value between axial and sagittal measurements of AAAs (ρ=0.23, P<0.001) and detection rates (ρ=0.01, P<0.001), though the correlation was very weak. Conclusions:This study identified a substantial incidence of AAAs on lumbar spine MRI scans, with a significant proportion of these cases going unreported by radiologists. Age and male sex were key factors influencing AAA prevalence, underscoring the need for targeted screening and management strategies that account for demographic differences.

INTRODUCTION:Endovascular techniques and materials have significantly expanded their application in the treatment of abdominal and thoraco-abdominal aortic lesions, allowing for the management of increasingly complex pathologies that may require cannulation of target vessels. The treatment of such diseases deserves a particular approach and dedicated materials, for which correct procedural planning is mandatory. In the last decades, the use of 3D printing technology as an assisting tool for preoperative rehearsal of complex cases has progressively widespread. AREAS COVERED:A review was performed about the use of 3D printing technology for the planning of endovascular repair of complex abdominal and thoraco-abdominal aortic lesions. Also, our experience of planning and simulation of an elective challenging endovascular procedure for a Crawford's type II thoraco-abdominal aortic aneurysm using a Cook Zenith® T-BranchTM endograft, leveraging a 3D-printed model of the patient-specific anatomy from the aortic arch to the common femoral artery, is herein described. EXPERT OPINION:The benefits of using 3D printing technologies as an assistive tool in planning complex endovascular repairs of abdominal and thoraco-abdominal aortic lesions have been well-documented in the literature, including their application in urgent cases. However, further research and development are necessary to overcome the current limitations of this potentially highly valuable technology.