Aortic Aneurysm Research Articles

Estimated aortic pulse wave velocity predicts adverse events in females with thoracic aortic aneurysms

Abstract Introduction Despite being more common in males, thoracic aortic aneurysms (TAAs) have worse prognosis in females. Females with TAA are 3x more likely to experience acute aortic syndromes, and 40% more likely to die than their male counterparts, but mechanisms underlying this paradox are incompletely understood. The estimated aortic pulse wave velocity (e-PWV) is a marker of aortic stiffness that can be used widely due to its simplicity, as it does not require specialized equipment. We have previously shown that e-PWV was independently associated with faster TAA growth,(1) and that this association was twice as strong in females than males, but the role of e-PWV as a predictor of adverse outcomes in TAA remains unknown. Purpose We sought to evaluate the sex-specific association of e-PWV with adverse outcomes in patients with TAA. Methods We performed a prospective study of 102 males and 48 females with TAA. e-PWV was calculated according to validated equations utilizing age, mean arterial pressure, and presence/absence of cardiovascular risk factors.(2) The primary outcome was a composite of acute aortic syndromes, death, or elective aortic surgery. We used a Cox proportional hazard model to determine the independent association of e-PWV with the primary outcome, adjusted for age, BSA, aneurysm size and location, hypertension, and pulse pressure. Sex-specific models were performed if the interaction of sex*e-PWV was significant (P≤0.05). Univariate logistic regression models were performed to determine the c-statistic for e-PWV in predicting adverse outcomes, and the best e-PWV cutoff for this prediction was established based on sensitivity and specificity. Kaplan-Meier curves were performed using this cut-off. Results A summary of study design and results is presented in Picture 1. Mean age was 62±12 years, 70 (47%) had degenerative etiology, baseline aneurysm size was 46.3±4.3mm, and e-PWV was 9.5±1.9 m/s (not different between sexes, P>0.07 for each). Mean follow-up was 4.6±2.4 years in females and 5.5±2.3 years in males, P=0.031. The primary outcome occurred in 37 (25%) participants (3 dissections, 3 intramural hematomas, 1 aortic rupture, 22 elective surgical repairs and 11 deaths - 3 of which followed surgery). The interaction term sex*e-PWV was significant (P=0.0001), so sex-specific models were performed. e-PWV independently predicted the primary outcome in females (HR for 1m/s increase in e-PWV: 3.4; 95% confidence interval (CI): 1.1-14.7, P=0.033), but not in males (HR: 0.87; 95% CI: 0.50-1.51, P=0.622). In females, e-PWV had a c-statistic of 0.860 for the detection of the primary outcome, with a best e-PWV cutoff of 11.58 m/s (73% sensitivity, 92% specificity). Kaplan-Meier curves for the primary outcome in females using this cutoff are shown in Picture 2. Conclusion e-PWV independently predicts adverse outcomes in females with TAA, highlighting a novel marker for risk stratification and therapeutic targeting.Study summaryKaplan-Meier curves

Itga9 protects against thoracic aortic aneurysm or dissection

Abstract Background The thoracic aortic aneurysm or dissection (TAAD) is a fatal cardiovascular disease with unclear pathogenic mechanisms. Integrins are important in coordinating the transmembrane connections between the extracellular matrix (ECM) and cytoskeleton, contributing to pathological processes of various diseases. Integrin α9 (Itga9), one of the integrin family subunits, has emerged as critical for vascular homeostasis. However, the contribution of Itga9 to TAAD remains elusive. Purpose The present study aimed to determine the role of Itga9 in the development of TAAD and its underlying mechanisms. Methods Western blotting and immunofluorescence staining were used to evaluate ITGA9 expression in the human Standford-A AAD tissues and rodent model of TAAD. Beta-aminopropionitrile monofumarate (BAPN) was used to induce TAAD mouse model. Vascular smooth muscle cell (VSMC)-specific Itga9 knockout mice or adeno-associated virus (AAV)-treated Itga9 overexpressed mice were generated to detect the role of Itga9 in the progression of TAAD. RNA-sequencing analysis was performed to discern possible transcriptome changes in the aorta tissues of VSMC-specific Itga9 knockout mice after BAPN treatment. Primary mouse aortic VSMC culture, flow cytometry analysis, EdU incorporation assay, transmission electron microscopy, and autophagy flux experiments were performed to evaluate the function of Itga9 on VSMCs and uncover its downstream target. Results ITGA9 expression levels were reduced in the aorta tissues of Standford-A AAD patients and BAPN-induced TAAD mice. VSMC-specific deletion of Itga9 exacerbated the incidence of BAPN-induced TAAD in mice. Itga9 deficiency downregulated Valosin-containing protein (Vcp) expression in mice aorta and caused reduced autophagy biomarkers of LC3 after BAPN treatment. In the primary aortic VSMCs, Itga9 deficiency resulted in repressed autophagy, accelerated apoptosis, and reduced proliferation ability. Mechanistically, Itga9 recruited the transcription factor Pre-B-cell leukemia transcription factor 1 (Pbx1) to activate the Vcp and promote VSMC autophagy. Consistently, overexpression of Itga9 in vitro and in vivo rescued the autophagic change and protected against the TAAD progression by upregulating the expression of Pbx1 and Vcp. Conclusions Our findings indicate a critical role of Itga9 in the regulation of VSMC autophagy by controlling Pbx1-Vcp. The Itga9-Pbx1-Vcp axis may represent a novel therapeutic target against TAAD.

Safe and favorable prognosis of thoracic endovascular aortic repair for the low-risk patients with non-acute type B aortic dissection

ObjectivePreemptive thoracic endovascular aortic repair (TEVAR) has the potential to improve the prognosis of Stanford type B aortic dissection (TBAD), however it is important to determine whether it could be safely performed as a prophylactic treatment. This study aimed to determine the short- and long-term outcomes of preemptive TEVAR for uncomplicated TBAD with a small aortic aneurysm.DesignRetrospective multicenter analysis.MethodsWe analyzed 212 patients with medically treated uncomplicated subacute TBAD between July 2004 and October 2019 in two Japanese academic centers. The short- and long-term prognosis of patients who underwent preemptive TEVAR and the changes in aortic diameter over time after TEVAR were analyzed. Aorta-related complications, aortic-related death and postoperative complications were recorded and analyzed. Analysis was performed on an intension-to-treat basis.ResultsDuring follow-up, patients were divided into two groups: optimal medical treatment [OMT; n = 185 (87%)] and preemptive TEVAR [n = 27 (13%)]. In all cases, aortic enlargement was the reason for therapeutic intervention in the preemptive TEVAR group. Propensity score matching yielded a cohort of 27 control patients with OMT (group A) and 27 patients who underwent preemptive TEVAR (group B). Preoperative characteristics were similar between groups. In group B, only one patient developed type A dissection at a late stage and died from aortic rupture. Freedom from aortic-related death at 1/5/10 years was 100%/92%/92% in group B. Overall growth (mm/year) of max aorta was significantly smaller in the TEVAR group than in the control group (−3.7 ± 2.9 vs. 0.4 ± 5.6, p < 0.01), and the diameter of the false lumen was reduced (−8 ± 4.8 vs. −1.3 ± 8.0, p < 0.001).ConclusionsShort- and long-term outcomes of TEVAR for uncomplicated TBAD with a small aortic aneurysm were excellent, with few postoperative complications. After TEVAR, aortic remodeling was observed in the short term, suggesting that it may contribute to the prevention of aortic-related death due to rupture.

Comparison of open and hybrid endovascular repair for aortic arch: a multi-Centre study of 1052 adult patients.

We aimed to evaluate early and late outcomes by comparing open total arch repair and endovascular arch repair using proximal landing zone analysis in a multicentre cohort. From 2008 to 2019, patients treated surgically for aortic arch disease at six centres were included, excluding cases with type A aortic dissection, additional aortic root replacement, and extensive aortic aneurysm. In all patients and populations with proximal landing zone 0/1 (N = 144) and 2 (N = 187), early and late outcomes were compared using propensity score matching. A total of 1052 patients, including 331 (31%) and 721 (69%) undergoing endovascular arch repair and open total arch repair, respectively, were enrolled. After propensity score match (endovascular arch repair, 295, open total arch repair; 566), no significant difference was observed in in-hospital mortality rate (endovascular arch repair, 6.8%, open total arch repair, 6.2%; p = 0.716). Open total arch repair was associated with a lower risk of all-cause death (log-rank test; p = 0.010, hazard ratio 1.41 [95% confidence interval: 1.17-1.71]). The incidence of aorta-related death was higher in endovascular arch repair (Gray test; p = 0.030, hazard ratio; 1.44 [95% confidence interval; 1.20-1.73]). When compared to endovascular arch repair with proximal landing zone 0/1, open total arch repair was associated with lower risks of all-cause death (log-rank test; p < 0.001, hazard ratio; 2.04 [95% confidence interval; 1.43-2.90]) and aorta-related death (Gray's test; p = 0.002, hazard ratio; 1.67 [95% confidence interval; 1.25-2.24]). There was no difference in the risk of all-cause death (log-rank test; p = 0.961, HR; 0.99 [95% confidence interval; 0.67-1.46]) and aorta-related death (Gray's test; p = 0.55, hazard ratio; 1.31 [95% confidence interval; 1.03-1.67]) between endovascular arch repair with proximal landing zone 2 and open total arch repair. Open total arch repair was considered the first choice based on early and late results; however, endovascular arch repair may be a useful option if the proximal landing zone is limited to zone 2.

Variation in care in individuals hospitalised with abdominal aortic aneurysm in nine high-income countries: a cross-sectional cohort study

Abstract Background Abdominal aortic aneurysms (AAA) can be safely repaired using either endovascular aneurysm repair (EVAR) or open repair when intact, but after rupture morbidity and mortality are extremely high. Treatment patterns and outcomes for intact AAA are likely to differ between countries due to differences in AAA screening policies, health system capacity and payment approaches, and other factors, such as demographics and lifestyle, but are poorly studied. Methods We conducted a retrospective serial cross-sectional cohort study of adults aged ≥66 years hospitalised for with an intact AAA and repair procedure in the same admission between 2011 and 2019 in nine countries (US, Canada, England, Denmark, Netherlands, Switzerland, Taiwan, South Korea and Israel) using population-representative administrative data. We investigated age-sex standardised (to the 2019 US population) repair rates (open repair or EVAR) and health system performance measures, including hospital length of stay (LOS), 30-day readmission, and all-cause mortality (30 days and 1 year). Results The number of intact AAA hospital admissions between 2011 and 2019 ranged from 1,290 in Israel to 199,764 in the US. The rates of intact AAA repair per 1000 population varied between countries and over time, from 0.11 per 1000 (South Korea) to 0.69 per 1000 (US) in 2011 and from 0.14 per 1000 (Taiwan) to 0.57 per 1000 (the Netherlands) in 2019. Most countries saw a decline in the rate of AAA repair over the study period. The proportion repaired using open repair vs EVAR also varied widely across the countries. In the US, Israel and Taiwan open repair was used in 11% or fewer cases whereas in the remaining countries we observed open repair in 25.1 % (South Korea) to 56.7% (Denmark) of cases. (Figure 1) Mortality was generally higher following open repairs compared to EVAR in all countries. In 2019, following EVAR, 30-day mortality varied from 0.6% (8.1% at 1 year) in South Korea to 2.3% (11.7% at 1 year) in Israel and following open repair varied from 2.9 (4.4% at 1 year) in England to 7.6% (15.1% at 1 year) in the US. (Figure 2) Mean hospital LOS in 2019 ranged from 2.5 days (US) to 12.2 days (South Korea), following EVAR and from 9.1 days (Taiwan) to 21.5 days (South Korea) following open repair. The 30-day readmission rate in 2019 ranged from 8.1% (US) to 31.8% in Israel following EVAR and from 11.4% (US) to 22.2% (South Korea) following open repair. Conclusions We observed substantial between-country variation in surgical approaches, mortality, and health system performance measures for AAA. Further research is needed to understand and plan optimal, evidence-based AAA screening and treatment strategies.Rates of EVAR and open repairAdjusted 30-day all-cause mortality

Evaluation of aortic inflammation in marfan syndrome patients with 18-fluorodeoxyglucose positron emission and computed tomography

Abstract Background The role of inflammation in Marfan Syndrome (MS) has been well studied in current research. These studies have investigated the role of serum Interleukin 6 (IL-6), Transforming Growth Factor-b (TGF-b) and Macrophage Colony Stimulating Factor (MCSF) as biomarkers of disease severity and progression. Surgical repair is the recommended treatment of aortic aneurysms when aortic diameter reaches the indication threshold. It has been observed however that dissection may occur even before this threshold is reached. 18-fluorodeoxyglucose (18 F-FDG) positron emission tomography / computed tomography (PET/CT) is the gold standard imaging modality to noninvasively assess vascular inflammation. Purpose Our aim was to investigate whether MS patients have increased aortic wall inflammation as assessed by 18F-FDG PET/CT, and the relationship between aortic wall inflammation with serum levels of IL-6, TGF-b and MCSF. Methods The study population consisted of fifteen MS patients and seventeen sex and age matched controls. In all subjects, serum levels of circulating IL-6, TGF-b and MCSF were measured. In PET/CT, the arterial target-to-background ratio (TBR) was calculated for aortic root (AR), ascending aorta(As), aortic arch (AA) and descending aorta (DA). Also, all patients were assessed with transthoracic echocardiography where the diameters of AR, As, AA, and DA were estimated at baseline and were reexamined at the end of the follow up period. Results TBR for MS vs. controls was 2.17±0.75 vs 2.01±0.36, p=0.75 at AR; 2.15±0.67 vs 1.84±0.35, p=0.040 at As; 2.16±0.64 vs 1.70±0.25, p=0.03 at AA and 1.97±0.52 vs 1.83±0.42, p=0.23 at DA respectively. Additionally, Marfan patients had increased levels of serum biomarkers. However, this difference was statistically significant (SS) only for IL-6 serum levels; 2.17±0.46 vs 1.08±0.12 p=0.011 and IL-6 was SS associated with AR TBR (rho=0.572, p=0.033), As TBR (rho=0.604, p=0.022) and DA TBR (rho=0.714, p=0.004). Two of our patients were operated due to severe dilatation of the aortic root and the surgical specimens showed aortic wall inflammation of moderate severity along with fibrosis. Conclusion MS patients have increased of aortic wall inflammation as assessed by 18F-FDG PET/CT, a finding that highlights the role of inflammation in the pathway of disturbed TGF signaling. Further research is needed to determine its prognostic role and value in identifying patients with an indication for early intervention.

Mapping 18F-FDG PET uptake in the aortic wall and thrombus

Abstract Background Positron Emission Tomography (PET) uptake allows for the assessment of molecular activity, being 18F-FDG uptake indicative of glucose metabolism. PET uptake is commonly quantified manually by drawing regions of interest, which is subjective, poorly-reproducible and may miss relevant information. Purpose To develop and test an image analysis method to quantify and map 18F-FDG uptake on the whole aortic wall and thrombus. Methods PET-MRI was acquired in patients with thoracic or abdominal aortic aneurysms. The aorta was semi-automatically segmented in the MR angiography using 3DSlicer, generating a surface mesh that was expanded by 3 mm inward and outward. PET uptake was interpolated over this volume with a uniform spatial resolution of 1 mm. By means of 9 reference points, the aortic wall was discretized into 52 (thoracic) or 80 (thoraco-abdominal) standardized regions (i.e. wall patches). For each aortic patch and for the whole thrombus volume, the target to background Ratio (TBR) was calculated by dividing the uptake by a reference uptake in the left atrium. Two observers segmented the aorta and thrombus, located the anatomical reference points and quantified TBR. Inter-observer agreement for segmentation and aortic wall discretization was evaluated in terms of the 95% Hausdorff Distance (HD) and Dice Score Coefficient (DSC), while both median and 95% TBR in each region were tested via intra-class correlation coefficient (absolute value, single measure). Results Data from 20 patients with thoracic or abdominal aneurysms were analysed, 10 of them presented thrombus. The reproducibility of the segmentation of the aorta (median HD 3.16 IQR [2.42 - 3.94] mm, DSC 0.90 [0.89 - 0.92]) and of the thrombus (HD 4.87 [3.51 - 8.45] mm, DSC 0.85 [0.80 - 0.87]) were excellent. The inter-observer agreement in the localization of reference points was good (HD 5.10 [3.29 - 8.73] mm), resulting in excellent overlapping of the standardized aortic wall patches (HD 3.80 [2.44 - 5.08] mm). Inter-observer agreement of median and 95% TBR in each aortic patch were excellent (ICC of 0.90 and 0.93, respectively, Figure 1), with minimal bias (Figure 2). Similarly, excellent interobserver reproducibility was observed for median and 95% TBR in the thrombus (ICC of 0.97 and 0.96, respectively, Figure 2). Conclusions A robust and reproducible image analysis method to map PET uptake along the aortic wall was developed, extending the possibilities to study aortic diseases molecular activity and its association with local aortic characteristics.

Trends in Regional Disparities of Cardiovascular Surgery and Mortality in South Korea

Abstract Objectives Regional disparities in cardiovascular care in South Korea have led to uneven patient outcomes. Although procedure access and needs are increasing, few studies have linked regional service availability to mortality rates. This study analyzed variation in utilization of major cardiovascular procedures by region and association with short-term mortality to provide better evidence on links between healthcare resources distribution and patient survival. Methods A cross-sectional study was conducted using nationwide claims data on patients who underwent coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), stent insertion, or aortic aneurysm resection in 2022. Regional variation was assessed by a Relevance Index (RI). The associations between regional RI and 30-day mortality were analyzed. Results The RI was lowest for aortic aneurysm resection (mean, 26.2; standard deviation, 26.1), indicating the most uneven regional distribution among the surgical procedures. Patients undergoing this procedure in regions with higher RIs showed significantly lower 30-day mortality (adjusted odds ratio [aOR], 0.73; 95% confidence interval, 0.55 to 0.96; p = 0.026) versus those with lower RIs. This suggests that cardiovascular surgery regional availability, as measured by RI, has an impact on mortality rates for certain complex surgical procedures. The RI was not associated with significant mortality differences for more widely available procedures like CABG (aOR, 0.96), PCI (aOR, 1.00), or stent insertion (aOR, 0.91). Conclusions Significant regional variation and underutilization of cardiovascular surgery were found, with reduced access linked to worse mortality for complex surgeries. Addressing disparities through cooperation among hospitals and policy efforts is warranted to improve outcomes. Key messages • This study analyzed regional variations in major cardiovascular procedures using the Relevance Index and investigated their impact on mortality rates within 30 days of admission. • Addressing regional disparities requires improved healthcare infrastructure and comprehensive networks of specialists to ensure timely and high-quality cardiovascular care across South Korea.

Systematic review of clinical effectiveness and safety of abdominal aortic aneurysm screening in men

Abstract Background Abdominal aortic aneurysm (AAA) is characterised by a bulging in the aortic wall. AAA is typically asymptomatic until aneurysm rupture, which is associated with a very high mortality rate (approximately 80%). In the context of an ageing population and increasing life expectancy, innovative approaches to early detection and intervention are needed. The aim of this review was to assess the clinical effectiveness and safety of one-time ultrasound screening for AAA in men. Methods Systematic searches were conducted in electronic databases and grey literature sources. The primary outcomes of interest were AAA-related mortality, AAA rupture, all-cause mortality, rate of surgical repair and safety. The following study designs were included: systematic reviews, randomised controlled trials (RCTs), comparative observational studies and population-based non-comparative observational studies. Results Results from a systematic review by the US Preventive Services Task Force analysed 4 population-based RCTs, showing that one-time population-based screening for AAA in men (≥ 65 years) led to significant reductions in AAA-related mortality (OR = 0.65, 95% CI: 0.57 to 0.74), AAA rupture (OR = 0.61, 95% CI: 0.54 to 0.69) and emergency surgeries (OR = 0.53, 95% CI: 95% CI: 0.44 to 0.64) at 13-15 years follow-up, relative to no screening. Separate to this systematic review an additional 24 studies reported on clinical effectiveness, safety and psychosocial harms of AAA screening. Limited evidence from these studies suggest screening was associated with a reduction in AAA-related mortality and rupture but also transient psychological distress in some cases. Conclusions One-time ultrasound screening in men ≥65 years appears to offer benefits in terms of reducing AAA ruptures and AAA-related mortality, though the balance of benefits and harms requires careful consideration. In an ageing population, AAA screening could be transformative, by reducing mortality and rupture risks. Key messages • One-time ultrasound screening for AAA in older men (≥ 65 years) can reduce AAA-related mortality and rupture. • In the context of an ageing population in Europe, AAA screening could be transformative, but benefits must be weighed against potential risks.

Potential effects of a human milk oligosaccharide 6'-sialyllactose on angiotensin II-induced aortic aneurysm via p90RSK/TGF-β/SMAD2 signaling pathway.

The aberrant phenotypic transformation of vascular smooth muscle cells (VSMCs) is a key factor in the formation of aortic aneurysm (AA). This study aimed to explore theeffects of 6'-sialyllactose (6'-SL), a human milk oligosaccharide, on angiotensin II (Ang II)-induced VSMC dysfunction and AA formation both in vitro and in vivo. An AA model was established in male C57BL/6 mice challenged with Ang II via osmotic pumps and a lysyl oxidase inhibitor, β-aminopropionitrile (BAPN), in drinking water. The mice were administered with 6'-SL, FMK (a p90RSK inhibitor), or losartan (as a positive control). In vitro, VSMCs were pretreated with 6'-SL before Ang II stimulation. We found that p90RSK inhibition abolished Ang II/BAPN-induced thoracic AA and abdominal AA formation. Treatment with 100mg/kg 6'-SL significantly attenuated Ang II/BAPN-induced aortic dilatation. 6'-SL attenuated Ang II-induced collagen deposition, calcification, and immune cell accumulation. Consistently, 6'-SL downregulated p-p90RSK, p90RSK, and p-SMAD2, and mitigated VSMC contractility loss, as indicated by α-SMA expression in vivo. Interestingly, Ang II-induced transforming growth factor-beta (TGF-β) signaling pathway was suppressed by p90RSK inhibition in VSMCs. 6'-SL treatment significantly reduced TGF-β/SMAD2 targets, including dedifferentiation markers such asosteopontin and vimentin, and elastin degradation factors MMP2 and MMP9. Overexpression of p90RSK in VSMCs enhanced TGF-β and abrogated the effects of 6'-SL. Furthermore, 6'-SL co-treatment abolished high phosphate-induced calcification in vitro via p90RSK/TGF-β signaling pathway. Altogether, our findings suggest that 6'-SL could be a potential therapeutic candidate for protecting against Ang II-induced AA formation by inhibiting the p90RSK/TGF-β/SMAD2 signaling pathway.

Conservative Management of mild symptomatic descending thoracic aneurysm – A case report with 1year follow-up

Background: The thoracic aorta is made up of the ascending, descending, aortic arch, and aortic root. An aneurysm forms when the artery's usual diameter increases by fifty percent. Thoracic aneurysms affect 10 of every 100,000 elderly adults and are less common than their abdominal counterparts. Patients with thoracic aortic aneurysms (TAAs) rarely experience symptoms, and 95% of TAA patients are asymptomatic. Case history: A 47-year-old male patient who had a medical history of hypertension, dyslipidemia, and smoking. During the first visit, the patient presented with two months of dull back pain. The patient's blood pressure was 180/110 mm of Hg. Our initial assessment involved taking an X-ray and an echocardiography of the patient's chest. The data from his echocardiography and chest reveals that he has a thoracic aneurysm. After a confirmatory CT scan, the diagnosis of thoracic aortic aneurysm was made. Conclusion: In our case report, conservative method was successful in the management of a mild symptomatic descending thoracic aorta aneurysm. However, the size, growth pace, and underlying cause of an aortic aneurysm might all affect whether doctors recommend surgery to repair it. If an aneurysm ruptures or dissects, immediate surgery may be required. J Shaheed Suhrawardy Med Coll 2023; 15(1): 87-90

A Decade-Long Retrospective Study of Factors Influencing Survival in Ruptured Abdominal Aortic Aneurysm

Background: Ruptured abdominal aortic aneurysm (rAAA) carries a high mortality risk, requiring rapid diagnosis and intervention. This study assesses various clinical factors influencing rAAA management outcomes in alignment with evolving guidelines from 2011 to 2024. Methods: A retrospective analysis of 62 rAAA patients treated at Vivantes Clinic, Berlin, from July 2014 to May 2024 was conducted. Data were obtained from medical records, focusing on vital parameters at admission and during treatment. Both numerical and categorical variables were analyzed to identify survival determinants. Results: The overall survival rate was 55%. Significant differences in systolic and diastolic blood pressures during surgery were noted between survivors and non-survivors, with lower pressures observed in non-survivors at critical surgical stages. Other vital signs showed no significant variations. Survival was significantly associated with gender, fluid therapy, and aneurysm location. Conclusions: Effective blood pressure management during surgery is crucial for improving survival in rAAA cases. This study emphasizes adherence to current clinical guidelines and highlights the need for ongoing research to fill existing knowledge gaps. Further investigations are essential to enhance patient care and outcomes in rAAA.

A Systematic Review of Renal Perfusion in Complex Abdominal Aortic Aneurysm Open Repair

Introduction: This systematic review aims to analyze the current literature regarding 30-day mortality and postoperative acute kidney disease (AKI) in complex abdominal aortic aneurysms (cAAAs), which included juxtarenal aortic aneurysm (JAA), suprarenal aortic aneurysm (SRAA), and type IV thoracoabdominal aortic aneurysm (TAAA) open surgery (OS), to evaluate the impact of renal perfusion on AKI and to try to define which is the best way to perform it. Methods: A literature search in PubMed and Cochrane Library was performed, and articles published from January 1986 to January 2024 reporting on JAA, SRAA, and TAAA type IV open surgery management were identified. Multicenter studies, single-center series, and case series with ≥10 patients were considered eligible. Comparisons of outcomes of patients who underwent OS for complex abdominal aortic aneurysms (cAAAs) with or without perfusion of the renal arteries were analyzed when available. The titles, abstracts, and full texts were evaluated by two authors independently. The primary outcomes included AKI and 30-day mortality rates. The new-onset dialysis rate was considered a secondary outcome. Results: A total of 295 articles were evaluated, and 21 were included, totaling 5708 patients treated for cAAAs with OS. The male patients totaled 4094 (71.7%), with a mean age of 70.35 ± 8.01 and a mean renal ischemia time of 32.14 ± 12.89 min. Data were collected and analyzed, at first in the entire cohort and then divided into two groups (no perfusion of the renal arteries—group A vs. selective perfusion—group B), with 2516 patients (44.08%) who underwent cAAAs OS without perfusion of the renal arteries and 3192 patients (55.92%) with perfusion. In group B, four types of renal perfusion were reported. Among the 21 studies included, 10 reported on selective renal perfusion in cAAA OS, with several types of fluids described: (1) “enriched” Ringer’s solution, (2) “Custodiol” (Istidine-tryptophan-ketoglutarate or Custodiol HTKsolution), (3) other cold (4 °C) solutions (i.e., several combinations of 4 °C isotonic heparinized balanced salt solution containing mannitol, sodium bicarbonate, and methylprednisolone), and (4) warm blood. Thirty-day mortality for patients in group A was 4.25% (107/2516) vs. 4.29% (137/3192) in group B. The reported incidence of AKI and new onset of dialysis was, respectively, 22.14% (557/2516) and 5.45% (137/2516) for group A and 22.49% (718/3192) and 4.32% (138/3192) for group B. A total of 579 patients presented with chronic kidney disease (CKD) at admission across all studies, which included 350 (13.91%) in group A vs. 229 (7.17%) in group B. Acute kidney injury, 30-day mortality, and new-onset dialysis rate were reported in four subgroups: (1) In the “Ringer” group, 30-day mortality was 2.52% (3/113), AKI affected 27.73% (33/119) of patients, and the new-onset dialysis rate was 2.52% (3/113). (2) In the “Custodiol” group, 30-day mortality was 3.70% (3/81), AKI affected 20.17% (24/81) of patients, and the new-onset dialysis rate was 2.46% (2/81). (3) In the “cold solutions” group (i.e., NaCl and mannitol), 30-day mortality was 4.38% (130/2966), AKI affected 21.81% (647/2966) of patients, and the new-onset dialysis rate was 4.48% (133/2966). (4) In the “Warm blood” group, 30-day mortality was 3.85% (1/26), AKI affected 53.84% (14/26) of patients, and the new-onset dialysis rate was 0% (0/26). Conclusions: This systematic review highlights the lack of standard definitions for AKI, CKD, and the type of renal perfusion. Despite similar results in terms of AKI and 30-day mortality, renal perfusion seems to be protective of the new-onset hemodialysis rate. Moreover, Custodiol appears to have lower rates of AKI and hemodialysis than the other perfusion types. A prospective randomized controlled trial to perform further subgroup analysis and research the various types of renal perfusion may be necessary to identify possible benefits.

The Influence of Material Properties and Wall Thickness on Predicted Wall Stress in Ascending Aortic Aneurysms: A Finite Element Study.

Finite element analysis (FEA) has been used to predict wall stress in ascending thoracic aortic aneurysm (ATAA) in order to evaluate risk of dissection or rupture. Patient-specific FEA requires detailed information on ATAA geometry, loading conditions, material properties, and wall thickness. Unfortunately, measuring aortic wall thickness and mechanical properties non-invasively poses a significant challenge, necessitating the use of non-patient-specific data in most FE simulations. This study aimed to assess the impact of employing non-patient-specific material properties and wall thickness on ATAA wall stress predictions. FE simulations were performed on 13 ATAA geometries reconstructed from computed tomography angiography (CTA) images. Patient-specific material properties and wall thicknesses were made available from a previous study where uniaxial tensile testing was performed on tissue samples obtained from the same patients. The ATAA wall models were discretised with hexahedral elements and prestressed. For each ATAA model, FE simulations were conducted using patient-specific material properties and wall thicknesses, and group-mean values derived from all tissue samples included in the same experimental study. Literature-based material property and wall thickness were also obtained from the literature and applied to 4 representative cases. Additional FE simulations were performed on these 4 cases by employing group-mean and literature-based wall thicknesses. FE simulations using the group-mean material property produced peak wall stresses comparable to those obtained using patient-specific material properties, with a mean deviation of 7.8%. Peak wall stresses differed by 20.8% and 18.7% in patients with exceptionally stiff or compliant walls, respectively. Comparison to results using literature-based material properties revealed larger discrepancies, ranging from 5.4% to 28.0% (mean 20.1%). Bland-Altman analysis showed significant discrepancies in areas of high wall stress, where wall stress obtained using patient-specific and literature-based properties differed by up to 674kPa, compared to 227kPa between patient-specific and group-mean properties. Regarding wall thickness, using the literature-based value resulted in even larger discrepancies in predicted peak stress, ranging from 24.2% to 30.0% (mean 27.3%). Again, using the group-mean wall thickness offered better predictions with a difference less than 5% in three out of four cases. While peak wall stresses were most affected by the choice of mechanical properties or wall thickness, the overall distribution of wall stress hardly changed. Our study demonstrated the importance of incorporating patient-specific material properties and wall thickness in FEA for risk prediction of aortic dissection or rupture. Our future efforts will focus on developing inverse methods for non-invasive determination of patient-specific wall material parameters and wall thickness.

Regional Stiffness and Hardening Indices: New Indicators Derived from Multidimensional Dynamic CTA for Aneurysm Risk Assessment.

Two indices, indicating the regional average stiffness and the pace of strain hardening respectively, are derived from the nonlinear stress-strain behavior obtained from biomechanical analysis of aneurysm. A comprehensive method based on electrocardiographic-gated multidimensional dynamic computed tomography angiography (MD CTA) is developed for extracting these mechanical characteristics in vivo. The proposed indices are evaluated by 26 cases including 9 healthy, one aortosclerosis, and 16 abdominal aortic aneurysm cases. The difference of SSI and dSSI value between aneurysmal and healthy groups is up to orders in magnitude. Significant correlation of these indices with the clinical indicator of aneurysm diameter is found. Logistic models based on these indices are capable to sharply discriminate the healthy and the aneurysmal arteries with AUC>0.98. This work introduces new tools and new indices for aortic mechanical assessment which may shed light on understanding the mechanical condition, pathological state and eventually benefit clinical decision-making.

A bibliometric and visualization analysis of global trends and frontiers on macrophages in abdominal aortic aneurysms research.

Macrophages are key regulators of the inflammatory and innate immune responses. Researchers have shown that aberrant expression of macrophages contributes to the development of abdominal aortic aneurysms (AAA). However, a comprehensive bibliometric analysis exploring the research status and knowledge mapping of this area is lacking. This study aimed to explore the research status, knowledge mapping and hotspots of macrophages in AAA research from a bibliometric perspective. In this study, we retrieved articles published between 2000 and 2022 on macrophages associated with AAA research from the Web of Science Core Collection (WoSCC) database. The retrieved literature data were further analyzed using Citespace and VOSviewer software. A total of 918 qualified publications related to AAA-associated macrophages were retrieved. The number of publications in this field has been increasing annually. China and the United States were the 2 main drivers in this field, contributing to more than 64% of the publications. In addition, the US had the most publications, top institutions, and expert researchers, dominating in research on macrophages in AAA. The Harvard University was the most productive institution, with 60 publications. The journal with the most publications was Arteriosclerosis, Thrombosis, and Vascular Biology (86). Daugherty Alan was the most prolific author (28 publications) and he was also the most cited co- author. Furthermore, the exploration of established animal models, macrophage-related inflammatory-microenvironment, macrophage-related immune mechanism, clinical translation and molecular imaging research remained future research directions in this field. Our findings offered new insights for scholars in this field. They will help researchers explore new directions for their work.

Deep learning-based segmentation of abdominal aortic aneurysms and intraluminal thrombus in 3D ultrasound images.

Ultrasound (US)-based patient-specific rupture risk analysis of abdominal aortic aneurysms (AAAs) has shown promising results. Input for these models is the patient-specific geometry of the AAA. However, segmentation of the intraluminal thrombus (ILT) remains challenging in US images due to the low ILT-blood contrast. This study aims to improve AAA and ILT segmentation in time-resolved three-dimensional (3D + t) US images using a deep learning approach. In this study a "no new net" (nnU-Net) model was trained on 3D + t US data using either US-based or (co-registered) computed tomography (CT)-based annotations. The optimal training strategy for this low-contrast data was determined for a limited dataset. The merit of augmentation was investigated, as well as the inclusion of low-contrast areas. Segmentation results were validated with CT-based geometries as the ground truth. The model trained on CT-based masks showed the best performance in terms of DICE index, Hausdorff distance, and diameter differences, covering a larger part of the AAA. With a higher accuracy and less manual input the model outperforms conventional methods, with a mean Hausdorff distance of 4.4mm for the vessel and 7.8mm for the lumen. However, visibility of the lumen-ILT interface remains the limiting factor, necessitating improvements in image acquisition to ensure broader patient inclusion and enable rupture risk assessment of AAAs in the future.

Porphyromonas gingivalis GroEL accelerates abdominal aortic aneurysm formation by matrix metalloproteinase-2 SUMOylation in vascular smooth muscle cells: A novel finding for the activation of MMP-2.

Infection is a known cause of abdominal aortic aneurysm (AAA), and matrix metalloproteases-2 (MMP-2) secreted by vascular smooth muscle cells (SMCs) plays a key role in the structural disruption of the middle layer of the arteries during AAA progression. The periodontal pathogen Porphyromonas gingivalis is highly associated with the progression of periodontitis. GroEL protein of periodontal pathogens is an important virulence factor that can invade the body through either the bloodstream or digestive tract and is associated with numerous systemic diseases. Although P. gingivalis aggravates AAA by increasing the expression of MMP-2 in animal studies, the molecular mechanism through which P. gingivalis regulates the expression of MMP-2 is still unknown and requires further investigation. In this study, we first confirmed through animal experiments that P. gingivalis GroEL promotes MMP-2 secretion from vascular SMCs, thereby aggravating Ang II-induced aortic remodeling and AAA formation. In addition, rat vascular SMCs and A7r5 cells were used to investigate the underlying mechanisms in vitro. The results demonstrated that GroEL can promote the interaction between the K639 site of MMP-2 and SUMO-1, leading to MMP-2 SUMOylation, which inhibits the reoccurrence of non-K639-mediated monoubiquitylation. Hence, the monoubiquitylation-mediated lysosomal degradation of MMP-2 is inhibited, consequently promoting MMP-2 stability and production. SUMOylation may facilitate intra-endoplasmic reticulum (ER) and Golgi trafficking of MMP-2, thereby enhancing its transport capacity. In conclusion, this is the first report demonstrating the presence of a novel posttranslational modification, SUMOylation, in the MMP family, suggesting that P. gingivalis GroEL may exacerbate AAA formation by increasing MMP-2 production through SUMOylation in vascular SMCs. This study also provides a novel perspective on the role of SUMOylation in MMP-2-induced systemic diseases.

Transmission line model as a digital twin for abdominal aortic aneurysm patients

We investigated the potential of the transmission line model as a digital twin of aneurysmal aorta by comparatively analyzing how a uniform lossless tube-load model were fitted to the carotid and femoral artery tonometry waveforms pertaining to (i) 79 abdominal aortic aneurysm (AAA) patients vs their matched controls (CON) and (ii) 35 AAA patients before vs after endovascular aneurysm repair (EVAR). The uniform lossless tube-load model fitted the tonometry waveforms pertaining to AAA as well as CON and EVAR. In addition, the parameters in the tube-load model exhibited physiologically explainable changes: when normalized, both pulse transit time and reflection coefficient increased with AAA and decreased after EVAR, which can be explained by the increase in arterial compliance and the decrease in arterial inertance due to the aortic expansion associated with AAA. In sum, the tube-load model may have the potential as a digital twin to enable personalized AAA monitoring.

The impact of large aneurysm diameter on the outcomes of thoracoabdominal aneurysm repair by fenestrated and branched endografts.

Aim of the study was to analyze the impact of preoperative thoraco-abdominal aneurysm diameter on the outcomes of fenestrated/branched endografting. Patients underwent endovascular thoraco-abdominal repair at 2 European centers (2011-2021) were analyzed. Median diameter was calculated; third quartile was considered as cut-off. Outcomes were compared in two groups based on the diameter value. Primary end-points were technical success, spinal cord ischaemia and 30-day/in-hospital mortality. Survival, freedom-from-reintervention and target-visceral-vessels instability were follow-up outcomes. Out of 247 thoraco-abdominal aortic aneurysms, the median diameter was 65 mm, first quartile was 57 mm; third quartile was 80 mm, set as cut-off value. Fifty-nine(24%) patients had diameter ≥80mm. Custom-Made and off-the-shelf branched endograft were used in 160(65%) and 87(35%), respectively. Technical success was 93% (<80mm : 91% vs ≥80mm : 94%; P:0.47). Twenty-three(9%) patients had spinal injury (<80mm : 7% vs ≥80mm : 17%; P:0.03). Twenty-two(9%) patients died within 30-day/in-hospital (<80mm : 7%; vs ≥80mm : 15%; P:0.06). Multivariate analysis did not report pre-operative diameter ≥80mm as significant risk factor for primary end-points. The median follow-up was 13 (interquartile-range : 2-37) months and at 3-years survival and freedom from reintervention rates were 65% and 62%, respectively. After univariate and multivariate analysis preoperative diameter ≥80mm was considered an independent risk factor for reinterventions (HR : 1.9; 95% CI : 1.1-3.6; P:0.04), and for target visceral vessels instability (HR : 3.1; 95% CI : 1.3-5.1; P:0.04), occurred in 45(18%) cases. However after competing risk methods preoperative diameter did not show significance for follow-up results. A pre-operative thoraco-abdominal aortic aneurysm diameter greater than 80 mm has not a direct impact on early technical and clinical outcomes. Diameter ≥80mm is considered risk-factor for reinterventions and target-vessels instability considered separately during follow-up.