Vessel-based CTA-image to spatial anatomy registration using tracked catheter position data: preclinical evaluation of in vivo accuracy.

Electromagnetic tracking of endovascular instruments has the potential to substantially decrease radiation exposure of patients and personnel. In this study, we evaluated the in vivo accuracy of a vessel-based method to register preoperative computed tomography angiography (CTA) images to physical coordinates using an electromagnetically tracked guidewire. Centerlines of the aortoiliac arteries were extracted from preoperative CTA acquired from five swine. Intravascular positions were obtained from an electromagnetically tracked guidewire. An iterative-closest-point algorithm registered the position data to the preoperative image centerlines. To evaluate the registration accuracy, a guidewire was placed inside the superior mesenteric, left and right renal arteries under fluoroscopic guidance. Position data was acquired with electromagnetic tracking as the guidewire was pulled into the aorta. The resulting measured positions were compared to the corresponding ostia manually identified in the CTA images after applying the registration. The three-dimensional (3D) Euclidean distances were calculated between each corresponding ostial point, and the root mean square (RMS) was calculated for each registration. The median 3D RMS for all registrations was 4.82 mm, with an interquartile range of 3.53-6.14 mm. A vessel-based registration of CTA images to vascular anatomy is possible with acceptable accuracy and encourages further clinical testing. RELEVANCE STATEMENT: This study shows that the centerline algorithm can be used to register preoperative CTA images to vascular anatomy, with the potential to further reduce ionizing radiation exposure during vascular procedures. KEY POINTS: Preoperative images can be used to guide the procedure without ionizing intraoperative imaging. Preoperative imaging can be the only imaging modality used for guidance of vascular procedures. No need to use external fiducial markers to register/match images and spatial anatomy. Acceptable accuracy can be achieved for navigation in a preclinical setting.

GP VI-Mediated Platelet Activation and Procoagulant Activity Aggravate Inflammation and Aortic Wall Remodeling in Abdominal Aortic Aneurysm.

BACKGROUND: Platelets play an important role in cardiovascular and cerebrovascular diseases. Abdominal aortic aneurysm (AAA) is a highly lethal, atherosclerosis-related disease with characteristic features of progressive dilatation of the abdominal aorta and degradation of the vessel wall, accompanied by chronic inflammation. Platelet activation and procoagulant activity play a decisive role in the AAA pathology as they might trigger AAA development in both mice and humans. METHODS: The present study investigated the impact of the major platelet collagen receptor GP (platelet glycoprotein) VI in pathophysiological processes underlying AAA initiation and progression. For experimental AAA induction in mice, PPE (porcine pancreatic elastase) and the external PPE model were used. RESULTS: Genetic deletion of GP VI offered protection of mice against aortic diameter expansion in experimental AAA. Mechanistically, GP VI deficiency resulted in decreased inflammation with reduced infiltration of neutrophils and platelets into the aortic wall. Furthermore, remodeling of the aortic wall was improved in the absence of GP VI, as indicated by reduced MMP (matrix metalloproteinase)-2/9 and OPN (osteopontin) plasma levels and an enhanced α-SMA (α-smooth muscle actin) content within the aortic wall, accompanied by reduced cell apoptosis. Consequently, an elevation in intima/media thickness and elastin content was observed in GP VI-deficient PPE mice, resulting in a significantly reduced aortic diameter expansion and reduced aneurysm incidence. In patients with AAA, enhanced plasma levels of soluble GP VI and fibrin, as well as fibrin accumulation within the intraluminal thrombus might serve as new biomarkers to detect AAA early. Moreover, we hypothesize that GP VI might play a role in procoagulant activity and thrombus stabilization via binding to fibrin. CONCLUSIONS: In conclusion, our results emphasize the potential need for a GP VI-targeted antiplatelet therapy to reduce AAA initiation and progression, as well as to protect patients with AAA from aortic rupture.

Insight in the (Phospho)proteome of Vascular Smooth Muscle Cells Derived From Patients With Abdominal Aortic Aneurysm Reveals Novel Disease Mechanisms.

BACKGROUND: Abdominal aortic aneurysm (AAA) is characterized by weakening and dilatation of the aortic wall in the abdomen. The aim of this study was to gain insight into cell-specific mechanisms involved in AAA pathophysiology by analyzing the (phospho)proteome of vascular smooth muscle cells derived from patients with AAA compared with those of healthy donors. METHODS: A (phospho)proteomics analysis based on tandem mass spectrometry was performed on vascular smooth muscle cells derived from patients with AAA (n=24) and healthy, control individuals (C-SMC, n=8). Following protein identification and quantification using MaxQuant, integrative inferred kinase activity analysis was used to calculate kinase activity scores. RESULTS: Expression differences between vascular smooth muscle cells derived from patients with AAA and healthy, control individuals were predominantly found in proteins involved in ECM (extracellular matrix) remodeling (THSD4 [thrombospondin type-1 domain-containing protein 4] and ADAMTS1 [A disintegrin and metalloproteinase with thrombospondin motifs 1]), energy metabolism (GYS1 [glycogen synthase 1] and PCK2 [phosphoenolpyruvate carboxykinase 2, mitochondrial]), and contractility (CACNA2D1 [calcium voltage-dependent channel subunit α-2/δ-1] and TPM1 [tropomyosin α-1 chain]). Phosphorylation patterns on proteins related to actin cytoskeleton organization dominated the phosphoproteome of vascular smooth muscle cells derived from patients with AAA . Besides, phosphorylation changes on proteins related to energy metabolism (GYS1), contractility (PARVA [α-parvin], PPP1R12A [protein phosphatase 1 regulatory subunit 12A], and CALD1 [caldesmon 1]), and intracellular communication (GJA1 [gap junction α-1 protein]) were seen. Kinase activity of NUAK1 (NUAK family SNF1-like kinase 1), FYN (tyrosine-protein kinase Fyn), MAPK7 (mitogen-activated protein kinase 7), and STK10 (serine/threonine kinase 10) was different in vascular smooth muscle cells derived from patients with AAA compared with those from healthy, control individuals. CONCLUSIONS: This study revealed changes in expression and phosphorylation levels of proteins involved in various processes responsible for AAA progression and development (eg, energy metabolism, ECM remodeling, actin cytoskeleton organization, contractility, intracellular communication, and cell adhesion). These newly identified proteins, phosphosites, and related kinases provide further insight into the underlying mechanism of vascular smooth muscle cell dysfunction within the aneurysmal wall. Our omics data thereby offer the opportunity to study the relevance, either as drug target or biomarker, of these proteins in AAA development.

Small AAAs: Recommendations for Rodent Model Research for the Identification of Novel Therapeutics.

CLINICAL PROBLEM: Most abdominal aortic aneurysms (AAAs) are small with low rupture risk (<1%/y) when diagnosed but slowly expand to ≥55 mm and undergo surgical repair. Patients and clinicians require medications to limit AAA growth and rupture, but drugs effective in animal models have not translated to patients. RECOMMENDATIONS FOR INCREASING TRANSLATION FROM MOUSE MODELS: Use models that simulate human AAA tissue pathology, growth patterns, and rupture; focus on the clinically relevant outcomes of growth and rupture; design studies with the rigor required of human clinical trials; monitor AAA growth using reproducible ultrasound; and perform studies in both males and females. SUMMARY OF STRENGTHS AND WEAKNESSES OF MOUSE MODELS: The aortic adventitial elastase oral ß-aminopropionitrile model has many strengths including simulating human AAA pathology and modeling prolonged aneurysm growth. The Ang II (angiotensin II) model performed less well as it better simulates acute aortic syndrome than AAA. The elastase plus TGFß (transforming growth factor-ß) blocking antibody model displays a high rupture rate, making prolonged monitoring of AAA growth not feasible. The elastase perfusion and calcium chloride models both display limited AAA growth.

2023 Update on Vascular Anesthesia.

The authors thank the editors for this opportunity to review the recent literature on vascular surgery and anesthesia and provide this clinical update. The last in a series of updates on this topic was published in 2019.1 This review explores evolving discussions and current trends related to vascular surgery and anesthesia that have been published since then. The focus is on the major points discussed in the recent literature in the following areas: carotid artery surgery, infrarenal aortic surgery, peripheral vascular surgery, and the preoperative evaluation of vascular surgical patients.

Temporal Trends and Outcomes of Abdominal Aortic Aneurysm Care in the United States.

BACKGROUND: Endovascular aortic aneurysm repair (EVAR) has had a dynamic impact on abdominal aortic aneurysm (AAA) care, often supplanting open AAA repair (OAR). Accordingly, US AAA management is often highlighted by disparities in patient selection and guideline compliance. The purpose of this analysis was to define secular trends in AAA care. METHODS: The Society for Vascular Surgery Vascular Quality Initiative was queried for all EVARs and OARs (2011-2021). End points included procedure utilization, change in mortality, patient risk profile, Society for Vascular Surgery-endorsed diameter compliance, off-label EVAR use, cross-clamp location, blood loss, in-hospital complications, and post-EVAR surveillance missingness. Linear regression was used without risk adjustment for all end points except for mortality and complications, for which logistic regression with risk adjustment was used. RESULTS: In all, 66 609 EVARs (elective, 85% [n=55 805] and nonelective, 15% [n=9976]) and 13 818 OARs (elective, 70% [n=9706] and nonelective, 30% [n=4081]) were analyzed. Elective EVAR:OAR ratios were increased (0.2 per year [95% CI, 0.01-0.32]), while nonelective ratios were unchanged. Elective diameter threshold noncompliance decreased for OAR (24%→17%; P=0.01) but not EVAR (mean, 37%). Low-risk patients increasingly underwent elective repairs (EVAR, +0.4%per year [95% CI, 0.2-0.6]; OAR, +0.6 points per year [95% CI, 0.2-1.0]). Off-label EVAR frequency was unchanged (mean, 39%) but intraoperative complications decreased (0.5% per year [95% CI, 0.2-0.9]). OAR complexity increased reflecting greater suprarenal cross-clamp rates (0.4% per year [95% CI, 0.1-0.8]) and blood loss (33 mL/y [95% CI, 19-47]). In-hospital complications decreased for elective (0.7% per year [95% CI, 0.4-0.9]) and nonelective EVAR (1.7% per year [95% CI, 1.1-2.3]) but not OAR (mean, 42%). A 30-day mortality was unchanged for both elective OAR (mean, 4%) and EVAR (mean, 1%). Among nonelective OARs, an increase in both 30-day (0.8% per year [95% CI, 0.1-1.5]) and 1-year mortality (0.8% per year [95% CI, 0.3-1.6]) was observed. Postoperative EVAR surveillance acquisition decreased (67%→49%), while 1-year mortality among patients without imaging was 4-fold greater (9.2% versus imaging, 2.0%; odds ratio, 4.1 [95% CI, 3.8-4.3]; P<0.0001). CONCLUSIONS: There has been an increase in EVAR and a corresponding reduction in OAR across the United States, despite established concerns surrounding guideline adherence, reintervention, follow-up, and cost. Although EVAR morbidity has declined, OAR complication rates remain unchanged and unexpectedly high. Opportunities remain for improving AAA care delivery, patient and procedure selection, guideline compliance, and surveillance.

Unravelling CD4+ T cell diversity and tissue adaptation of Tregs in abdominal aortic aneurysms through single-cell sequencing.

Immune cell infiltration is a significant pathological process in abdominal aortic aneurysms (AAA). T cells, particularly CD4+ T cells, are essential immune cells responsible for substantial infiltration of the aorta. Regulatory T cells (Tregs) in AAA have been identified as tissue-specific; however, the time, location, and mechanism of acquiring the tissue-specific phenotype are still unknown. Using single-cell RNA sequencing (scRNA-seq) on CD4+ T cells from the AAA aorta and spleen, we discovered heterogeneity among CD4+ T cells and identified activated, proliferating and developed aorta Tregs. These Tregs originate in the peripheral tissues and acquire the tissue-specific phenotype in the aorta. The identification of precursors for Tregs in AAA provides new insight into the pathogenesis of AAA.

LXRα Promotes Abdominal Aortic Aneurysm Formation Through UHRF1 Epigenetic Modification of miR-26b-3p.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a severe aortic disease without effective pharmacological approaches. The nuclear hormone receptor LXRα (liver X receptor α), encoded by the NR1H3 gene, serves as a critical transcriptional mediator linked to several vascular pathologies, but its role in AAA remains elusive. METHODS: Through integrated analyses of human and murine AAA gene expression microarray data sets, we identified NR1H3 as a candidate gene regulating AAA formation. To investigate the role of LXRα in AAA formation, we used global Nr1h3-knockout and vascular smooth muscle cell-specific Nr1h3-knockout mice in 2 AAA mouse models induced with angiotensin II (1000 ng·kg·min; 28 days) or calcium chloride (CaCl2; 0.5 mol/L; 42 days). RESULTS: Upregulated LXRα was observed in the aortas of patients with AAA and in angiotensin II- or CaCl2-treated mice. Global or vascular smooth muscle cell-specific Nr1h3 knockout inhibited AAA formation in 2 mouse models. Loss of LXRα function prevented extracellular matrix degeneration, inflammation, and vascular smooth muscle cell phenotypic switching. Uhrf1, an epigenetic master regulator, was identified as a direct target gene of LXRα by integrated analysis of transcriptome sequencing and chromatin immunoprecipitation sequencing. Susceptibility to AAA development was consistently enhanced by UHRF1 (ubiquitin-like containing PHD and RING finger domains 1) in both angiotensin II- and CaCl2-induced mouse models. We then determined the CpG methylation status and promoter accessibility of UHRF1-mediated genes using CUT&Tag (cleavage under targets and tagmentation), RRBS (reduced representation bisulfite sequencing), and ATAC-seq (assay for transposase-accessible chromatin with sequencing) in vascular smooth muscle cells, which revealed that the recruitment of UHRF1 to the promoter of miR-26b led to DNA hypermethylation accompanied by relatively closed chromatin states, and caused downregulation of miR-26b expression in AAA. Regarding clinical significance, we found that underexpression of miR-26b-3p correlated with high risk in patients with AAA. Maintaining miR-26b-3p expression prevented AAA progression and alleviated the overall pathological process. CONCLUSIONS: Our study reveals a pivotal role of the LXRα/UHRF1/miR-26b-3p axis in AAA and provides potential biomarkers and therapeutic targets for AAA.

Ganglioside GM3 Protects Against Abdominal Aortic Aneurysm by Suppressing Ferroptosis.

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

Endograft position and endoleak detection after endovascular abdominal aortic repair with low-field tiltable MRI: a feasibility study.

BACKGROUND: Abdominal aortic endoleaks after endovascular aneurysm repair might be position-dependent, therefore undetectable using supine imaging. We aimed to determine the feasibility and benefit of using a low-field tiltable magnetic resonance imaging (MRI) scanner allowing to study patients who can be imaged in both supine and upright positions of endoleaks. METHODS: Ten EVAR patients suspected of endoleak based on ultrasound examination were prospectively included. MRI in upright and supine positions was compared with routine supine computed tomography angiography (CTA). Analysis was performed through (1) subjective image quality assessment by three observers, (2) landmark registration between MRI and CTA scans, (3) Euclidean distances between renal and endograft landmarks, and (4) evaluation of endoleak detection on MRI by a consensus panel. Statistical analysis was performed by one-way repeated measures analysis of variance. RESULTS: The image quality of upright/supine MRI was inferior compared to CTA. Median differences in both renal and endograft landmarks were approximately 6-7 mm between upright and supine MRI and 5-6 mm between supine MRI and CTA. In the proximal sealing zone of the endograft, no differences were found among all three scan types (p = 0.264). Endoleak detection showed agreement between MRI and CTA in 50% of the cases, with potential added value in only one patient. CONCLUSIONS: The benefit of low-field upright MRI for endoleak detection was limited. While MRI assessment was non-inferior to standard CTA in detecting endoleaks in selected cases, improved hardware and sequences are needed to explore the potential of upright MRI in patients with endoleaks. RELEVANCE STATEMENT: Upright low-field MRI has limited clinical value in detecting position-dependent endoleaks; improvements are required to fulfil its potential as a complementary modality in this clinical setting. KEY POINTS: • Upright MRI shows potential for imaging endoleaks in aortic aneurysm patients in different positions. • The image quality of upright MRI is inferior to current techniques. • Upright MRI complements CTA, but lacks accurate deformation measurements for clinical use. • Advancements in hardware and imaging sequences are needed to fully utilise upright MRI capabilities.

Preemptive Embolization of the Lumbar Arteries and Inferior Mesenteric Artery to Prevent Abdominal Aortic Aneurysm Enlargement Associated with Type 2 Endoleak Following Endovascular Aneurysm Repair.

Purpose: This study aims to evaluate the efficacy of preemptive embolization (PE) of the lumbar arteries (LAs) and inferior mesenteric artery (IMA) (PELI) for preventing abdominal aortic aneurysm (AAA) enlargement associated with type 2 endoleak (T2EL). Material and Methods: Patients who underwent endovascular aneurysm repair (EVAR) between January 2015 and December 2020 were classified into the control (without PE), IMA (PE of a patent IMA with a diameter ≥2.5 mm), and PELI (PE of patent LAs with a diameter ≥2 mm and IMA) groups. The rate of freedom from AAA enlargement following EVAR (enlargement ≥5 mm from pre-EVAR) was compared using the log-rank test. The prevalence of T2EL at 6 months and 1 year after EVAR was compared using Fisher's exact test. Results: The cumulative rates of freedom from AAA enlargement at 54 months after EVAR (maximum observational period in the PELI group) were as follows: control group, 77.5%; IMA group, 62.5%; and PELI group, 100%. The mean CT follow-up periods of the control, IMA, and PELI groups were 46.4 ± 22.3, 31.1 ± 20.6, and 22.9 ± 15.5 months, respectively. None of the 31 patients in the PELI group experienced AAA enlargement after EVAR, whereas 2 out of the 16 patients in the IMA group and 20 out of the 98 patients in the control group had AAA enlargement. No significant differences were observed in the rate of freedom from AAA enlargement (PELI group vs. IMA group, P = 0.11; PELI group vs. control group, P = 0.11). The prevalence of T2EL was significantly lower in the PELI group than in the control group at 6 months (13.6% in PELI group vs. 42.1% in control group, P = 0.02) and 1 year (14.3% in PELI group vs. 40.0% in control group, P = 0.04). Conclusions: PELI was significantly associated with a low prevalence of T2EL and may prevent T2EL-associated AAA enlargement.

CT analysis of aortic calcifications to predict abdominal aortic aneurysm rupture.

BACKGROUND: Abdominal aortic aneurysm (AAA) rupture prediction based on sex and diameter could be improved. The goal was to assess whether aortic calcification distribution could better predict AAA rupture through machine learning and LASSO regression. METHODOLOGY: In this retrospective study, 80 patients treated for a ruptured AAA between January 2001 and August 2018 were matched with 80 non-ruptured patients based on maximal AAA diameter, age, and sex. Calcification volume and dispersion, morphologic, and clinical variables were compared between both groups using a univariable analysis with p = 0.05 and multivariable analysis through machine learning and LASSO regression. We used AUC for machine learning and odds ratios for regression to measure performance. RESULTS: Mean age of patients was 74.0 ± 8.4 years and 89% were men. AAA diameters were equivalent in both groups (80.9 ± 17.5 vs 79.0 ± 17.3 mm, p = 0.505). Ruptured aneurysms contained a smaller number of calcification aggregates (18.0 ± 17.9 vs 25.6 ± 18.9, p = 0.010) and were less likely to have a proximal neck (45.0% vs 76.3%, p < 0.001). In the machine learning analysis, 5 variables were associated to AAA rupture: proximal neck, antiplatelet use, calcification number, Euclidian distance between calcifications, and standard deviation of the Euclidian distance. A follow-up LASSO regression was concomitant with the findings of the machine learning analysis regarding calcification dispersion but discordant on calcification number. CONCLUSION: There might be more to AAA calcifications that what is known in the present literature. We need larger prospective studies to investigate if indeed, calcification dispersion affects rupture risk. CLINICAL RELEVANCE STATEMENT: Ruptured aneurysms are possibly more likely to have their calcification volume concentrated in a smaller geographical area. KEY POINTS: • Abdominal aortic aneurysm (AAA) rupture prediction based on sex and diameter could be improved. • For a given calcification volume, AAAs with well-distributed calcification clusters could be less likely to rupture. • A machine learning model including AAA calcifications better predicts rupture compared to a model based solely on maximal diameter and sex alone, although it might be prone to overfitting.

VENUM (Vascular Education iN Undergraduate Medicine): a multicentre evaluation of undergraduate vascular education in the UK.

INTRODUCTION: Vascular surgery is a recognised surgical subspecialty covering an array of circulatory conditions predominately affecting geriatric and diabetic patients. As such, a wide breadth of clinicians will see patients with vascular pathologies, but it is unclear how detailed their knowledge base is. Key to this is the education of medical students, which has been poorly documented during undergraduate training in the UK. VENUM aimed to establish students' perceptions of vascular surgery and their confidence in performing vascular objective structured clinical examination (OCSE) skills. METHODS: During the academic year of 2022/2023, final-year medical students were invited to complete a JISC survey (collaborative authorship). Seventy-seven research leads were recruited to disseminate the survey. Quantitative and thematic analysis was used to assess the data. RESULTS: In total, 240 final-year medical students completed the survey (54% female; 26 medical schools represented). Forty-five per cent of students reported never having had a vascular placement, 24% had never completed a vascular-focused clinical examination and 26% reported low confidence in performing ankle brachial pressure index measurement. An assessment of peripheral arterial disease morbidity was answered correctly in 17% of respondents compared with 92% for angina (chi-square test p<0.001). Students perceived the specialty to be non-inclusive and that early exposure to vascular surgery was required for better engagement with the specialty. CONCLUSION: Students have experienced little exposure to vascular surgery. This may affect future recruitment to vascular surgery and overall knowledge of vascular conditions in UK-trained doctors, which may affect long-term patient management.

Loss of TIMP3, but not TIMP4, exacerbates thoracic and abdominal aortic aneurysm.

AIMS: Aorta exhibits regional heterogeneity (structural and functional), while different etiologies for thoracic and abdominal aortic aneurysm (TAA, AAA) are recognized. Tissue inhibitor of metalloproteinases (TIMPs) regulate vascular remodeling through different mechanisms. Region-dependent functions have been reported for TIMP3 and TIMP4 in vascular pathologies. We investigated the region-specific function of these TIMPs in development of TAA versus AAA. METHODS & RESULTS: TAA or AAA was induced in male and female mice lacking TIMP3 (Timp3-/-), TIMP4 (Timp4-/-) or in wildtype (WT) mice by peri-adventitial elastase application. Loss of TIMP3 exacerbated TAA and AAA severity in males and females, with a greater increase in proteinase activity, smooth muscle cell phenotypic switching post-AAA and -TAA, while increased inflammation was detected in the media post-AAA, but in the adventitia post-TAA. Timp3-/- mice showed impaired intimal barrier integrity post-AAA, but a greater adventitial vasa-vasorum branching post-TAA, which could explain the site of inflammation in AAA versus TAA. Severity of TAA and AAA in Timp4-/- mice was similar to WT mice. In vitro, Timp3 knockdown more severely compromised the permeability of human aortic EC monolayer compared to Timp4 knockdown or the control group. In aneurysmal aorta specimens from patients, TIMP3 expression decreased in the media in AAA, and in adventitial in TAA specimens, consistent with the impact of its loss in AAA versus TAA in mice. CONCLUSION: TIMP3 loss exacerbates inflammation, adverse remodeling and aortic dilation, but triggers different patterns of remodeling in AAA versus TAA, and through different mechanisms.

Treatment Outcomes of Patients With Ruptured Abdominal Aortic Aneurysms.

BACKGROUND: Ruptured abdominal aortic aneurysm (rAAA) is a serious complication of abdominal aortic aneurysm associated with high operative mortality and morbidity rates. The present study evaluated the perioperative and long-term outcomes of Korean patients with rAAA based on national health insurance claims data. METHODS: The National Health Insurance Service (NHIS) database was searched retrospectively to identify patients with rAAA who underwent endovascular aneurysm repair (EVAR) and open surgical repair (OSR) from 2009 to 2018. Perioperative (≤ 30 days), early postoperative (≤ 3 month), and long-term (> 3 month) survival, reinterventions, and complications were assessed. RESULTS: The search identified 1,034 patients with rAAA, including 594 who underwent EVAR and 440 who underwent OSR. When the study period was divided into two, the total numbers of patients with rAAA, patients who underwent EVAR, and octogenarians were higher during the second half. The perioperative mortality rate was 29.8% in the EVAR and 35.0% in the OSR group (P = 0.028). Hartmann's procedure for bowel infarction was performed more frequently in the OSR than in the EVAR group (adjusted odds ratio, 6.28; 95% confidence interval [CI], 2.33-21.84; P = 0.001), but other complication rates did not differ significantly. All-cause mortality during the entire observation period did not differ significantly in the EVAR and OSR groups (adjusted hazard ratio, 1.17; 95% CI, 0.98-1.41; P = 0.087). Abdominal aortic aneurysm-related reintervention rate was significantly lower in the OSR group (adjusted hazard ratio, 0.31; 95% CI, 0.14-0.70; P = 0.005). CONCLUSION: Although EVAR showed somewhat superior perioperative outcomes for rAAA, the long-term outcomes of EVAR after excluding initial 3 months were significantly worse than OSR. When anatomically feasible for both treatments, the perioperative mortality risk and reasonable prospects of long-term survival should be considered in rAAA.

Association of HIV Infection and Incident Abdominal Aortic Aneurysm Among 143 001 Veterans.

BACKGROUND: People with HIV (PWH) have an increased risk of cardiovascular disease. Previous cross-sectional data suggest there is a higher prevalence of abdominal aortic aneurysm (AAA) in PWH than in those without HIV. Whether PWH have an increased risk of incident AAA compared with those without HIV is unknown. METHODS: We analyzed data among participants without prevalent AAA from the Veterans Aging Cohort Study, a prospective, observational, longitudinal cohort of veterans with HIV matched 1:2 with veterans without HIV infection. We calculated AAA rates by HIV status and assessed the association between HIV infection and incident AAA using Cox proportional hazards models. We defined AAA using the International Classification of Diseases, 9th or 10th revision, or Current Procedural Terminology codes and adjusted all models for demographic characteristics, cardiovascular disease risk factors, and substance use. Secondary analyses examined the association between time-varying CD4+ T-cell count or HIV viral load and incident AAA. RESULTS: Among 143 001 participants (43 766 with HIV), over a median follow-up of 8.7 years, there were 2431 incident AAA events (26.4% among PWH). Rates of incident AAA per 1000 person-years were similar among PWH (2.0 [95% CI, 1.9-2.2]) and people without HIV (2.2 [95% CI, 2.1-2.3]). There was no evidence that HIV infection increased the risk of incident AAA compared with no HIV infection (adjusted hazard ratio, 1.02 [95% CI, 0.92-1.13]). In adjusted analyses with time-varying CD4+ T-cell counts or HIV viral load, PWH with CD4+ T-cell counts <200 cells/mm3 (adjusted hazard ratio, 1.29 [95% CI, 1.02-1.65]) or HIV viral load ≥500 copies/mL (adjusted hazard ratio, 1.29 [95% CI, 1.09-1.52]) had an increased risk of AAA compared with those without HIV. CONCLUSIONS: HIV infection is associated with an increased risk of AAA among those with low CD4+ T-cell counts or elevated HIV viral load over time.