Silencing IL2RB attenuates abdominal aortic aneurysm-related pathology in experimental models by partially restoring mitochondrial homeostasis

Outcomes of unibody endoprosthesis for treatment of aortic aneurysmal pathology and aortoiliac occlusive disease.

Approval of medical devices is typically based on data from relatively small clinical studies with a highly selected patient population. Postmarket surveillance is required by regulatory bodies after approval to collect and evaluate experience gained from real world use in larger and unselected populations. Terumo Aortic is a manufacturer of off-the-shelf and custom-made stent-grafts for endovascular repair of thoracic and abdominal aortic pathologies and is assessing device performance in a large registry. A multiarm, multicenter, open label, prospective observational registry designed to obtain both short- and long-term safety and performance data on the use of standard and custom-made Terumo Aortic endovascular devices in patients with thoracic and abdominal aortic pathologies. Eligibility requirements are minimal, and a standard-of-care protocol will ensure real-world evidence is collected as far as 10 years. Challenges to this research reflect its real-world nature such as differences in standard of care between centers and geographies, varying levels of experience and expertise with the devices or techniques, all-comer populations that may not always be comparable, and a design specifically limited to a single manufacturer. Advantages of this registry design include long-term follow-up, different modules to collect standardized outcomes across pathologies and global reach to reflect practice in many different geographies with a wide range of latest-generation endovascular devices. This protocol is a large endovascular registry of all aortic pathologies that are treated by both off-the-shelf and custom-made Terumo Aortic products. It is ambitious in scope and projection and will be part of an overall response involving patients, physicians, and manufacturers to answer the remaining questions of endovascular aortic repair, contribute to continuing improvement of the techniques and technologies, and present an accurate picture of outcomes with latest generation stent-graft devices.Clinical ImpactThis large, long-term registry will generate robust real-world evidence on the safety and performance of both standard and custom-made Terumo Aortic endovascular devices in treating thoracic and abdominal aortic pathologies. By including a broad, minimally selected patient population across diverse global centers, the study mirrors everyday clinical practice and helps bridge the gap between clinical trials and real-world outcomes. Its findings will inform clinical decision-making, support regulatory compliance, and guide ongoing device development. Ultimately, the registry aims to enhance patient care by improving the understanding of endovascular treatment effectiveness and long-term durability in heterogeneous populations.

The purpose of this study was to examine the immediate and midterm outcomes of percutaneous endovascular repair of thoracic and abdominal aortic pathology. Between December 2003 and June 2005, 21 patients (mean age: 60.4 +/- 17.1 years; 15 males, 6 females) underwent endovascular stent-graft insertion for thoracic (n = 13) or abdominal aortic (n = 8) pathology. Preprocedural computed tomographic angiography (CTA) was performed to assess the suitability of aorto-iliac and common femoral artery (CFA) anatomy, including the degree of CFA calcification, for total percutaneous aortic stent-graft repair. Percutaneous access was used for the introduction of 18- to 26-Fr delivery devices. A 'preclose' closure technique using two Perclose suture devices (Perclose A-T; Abbott Vascular) was used in all cases. Data were prospectively collected. Each CFA puncture site was assessed via clinical examination and CTA at 1, 6, and 12 months, followed by annual review thereafter. Minimum follow-up was 36 months. Outcome measures evaluated were rates of technical success, conversion to open surgical repair, complications, and late incidence of arterial stenosis at the site of Perclose suture deployment. A total of 58 Perclose devices were used to close 29 femoral arteriotomies. Outer diameters of stent-graft delivery devices used were 18 Fr (n = 5), 20 Fr (n = 3), 22 Fr (n = 4), 24 Fr (n = 15), and 26 Fr (n = 2). Percutaneous closure was successful in 96.6% (28/29) of arteriotomies. Conversion to surgical repair was required at one access site (3.4%). Mean follow-up was 50 +/- 8 months. No late complications were observed. By CT criteria, no patient developed a >50% reduction in CFA caliber at the site of Perclose deployment during the study period. In conclusion, percutaneous aortic stent-graft insertion can be safely performed, with a low risk of both immediate and midterm access-related complications.

Objective: Fludrocortisone, a corticosteroid, is used to treat adrenocortical insufficiency. In a previous study to determine associations between fludrocortisone-induced high blood pressure and angiotensin regulation, we observed aortic aneurysms in some fludrocortisone-infused mice. The purpose of this study was to investigate fludrocortisone-induced aortic pathologies in normocholesterolemic and hypercholesterolemic mice. Methods and Results: To determine whether fludrocortisone induces aortic aneurysms in normocholesterolemic mice, male C57BL/6J at 8 - 9 weeks of age were infused with either vehicle (85% polyethylene glycol 400 (PEG-400) and 15% dimethyl sulfoxide (DMSO); N=5) or fludrocortisone (12 mg/kg/day dissolved in 85% PEG-400 and 15% DMSO; N=15) for 28 days. Fludrocortisone-infused mice had higher systolic blood pressure, compare to mice infused with vehicle. Fludrocortisone induced aortic pathologies in 4 of 15 mice with 3 having pathologies in the ascending/arch region and 1 having pathology in both the ascending and descending thoracic aorta. No pathologies were noted in abdominal aortas. To determine whether hypercholesterolemia augments fludrocortisone-induced aortic pathologies, we infused either vehicle (N=5/group) or fludrocortisone (N=15/group) into male ApoE -/- mice fed a normal diet or LDL receptor -/- mice fed either normal or Western diet. Fludrocortisone increased systolic blood pressure, irrespective of mouse strain or diet. In ApoE -/- mice infused with fludrocortisone, 2 of 15 had ascending aortic pathologies, but no mice had abdominal aortic pathologies. In LDL receptor -/- mice fed normal diet, 4 had ascending/arch aortic pathologies, 1 had pathologies in the ascending, arch and abdominal regions. In LDL receptor -/- mice fed Western diet, 2 died of aortic rupture, 4 had ascending/arch aortic pathologies, and 1 had pathologies in the ascending, arch and suprarenal aortic regions. Aortic pathologies were hemorrhage, wall thickening or thinning, or dilation. Given the low incidence, no quantification of aortic pathologies reached statistical significance. Conclusion: Fludrocortisone induces aortic pathologies with low incidence in both normo- and hypercholesterolemic mice.

Background Endovascular techniques have revolutionised the therapy of abdominal and thoracoabdominal aortic disease. For infrarenal abdominal aortic aneurysm, the endovascular aortic repair has become a standard for elective and emergent cases. In complex abdominal or thoracoabdominal aortic pathologies, involving reno-visceral vessels, there are technical challenges for open and endovascular surgery. Due to high mortality and morbidity of open surgery of complex aortic lesions, especially in emergent cases, endovascular techniques have developed as well. Results Endovascular treatment options for complex aortic pathologies are fenestrated and branched stent grafts and the chimney graft technique. In elective cases, fenestrated and branched stent grafts are ordered as "custom-made" devices but planning, production and delivery takes up to approximately 12 weeks. For urgent cases, there recently only exists one 4-vessel branched "off-the-shelf" stent graft, that fits only about 60% of patients' anatomy in complex abdominal or thoracoabdominal aneurysm cases. As an alternative for these patients, "surgeon-modified" stent grafts are a treatment option. Here, a commercially available stent graft is modified with the needed fenestrations and branches for the visceral vessel prior to the operation. Compared to off-the-shelf stent grafts, the surgeon-modified stent grafts have similar results for mortality and morbidity. Conclusion As long as off-the-shelf devices for a larger variety of abdominal and thoracoabdominal anatomy are available, surgeon-modified stent grafts are a good treatment alternative for urgent complex abdominal and thoracoabdominal aortic pathologies in high-risk patients.

Midterm Results With Endovascular Approach to Abdominal Aortic Pathologies in Behçet’s Disease

Background and Objective: In an experiment designed to explore the mechanisms of fludrocortisone-induced high blood pressure, we serendipitously observed aortic aneurysms in mice infused with fludrocortisone. The purpose of this study was to investigate whether fludrocortisone induces aortic pathologies in both normocholesterolemic and hypercholesterolemic mice. Methods and Results: Male adult C57BL/6J mice were infused with either vehicle (85% polyethylene glycol 400 (PEG-400) and 15% dimethyl sulfoxide (DMSO); n = 5) or fludrocortisone (12 mg/kg/day dissolved in 85% PEG-400 and 15% DMSO; n = 15) for 28 days. Fludrocortisone-infused mice had higher systolic blood pressure, compared to mice infused with vehicle. Fludrocortisone induced aortic pathologies in 4 of 15 mice with 3 having pathologies in the ascending and aortic arch regions and 1 having pathology in both the ascending and descending thoracic aorta. No pathologies were noted in abdominal aortas. Subsequently, we infused either vehicle (n = 5/group) or fludrocortisone (n = 15/group) into male ApoE −/− mice fed a normal laboratory diet or LDL receptor −/− mice fed either normal or Western diet. Fludrocortisone increased systolic blood pressure, irrespective of mouse strain or diet. In ApoE −/− mice infused with fludrocortisone, 2 of 15 mice had ascending aortic pathologies, but no mice had abdominal aortic pathologies. In LDL receptor −/− mice fed normal diet, 5 had ascending/arch pathologies and 1 had pathologies in the ascending, arch, and suprarenal aortic regions. In LDL receptor −/− mice fed Western diet, 2 died of aortic rupture in either the descending thoracic or abdominal region, and 2 of the 13 survived mice had ascending/arch aortic pathologies. Aortic pathologies included hemorrhage, wall thickening or thinning, or dilation. Only ascending aortic diameter in LDLR −/− mice fed Western diet reached statistical significance, compared to their vehicle. Conclusion: Fludrocortisone induces aortic pathologies independent of hypercholesterolemia. As indicated by the findings in mouse studies, people who are taking or have taken fludrocortisone might have an increased risk of aortic pathologies.

Ultrasound and CT angiography are common diagnostic methods of abdominal aortic pathologies. In the last decade, hybrid methods (PET/CT, PET/MRI) have become more common in this diagnostic algorithm. Originally they were indicated in malignancies or inflammatory processes. Currently, efforts are developed to visualize possible local inflammatory activity in the aortic wall and thus to assess acertain “disease activity” with the goal to anticipate further development of aortic pathology. The aim of our study was to analyze potential benefits of hybrid methods in predicting abdominal aortic pathology progression. In this prospective, open-label, observational study we examined 75 patients referred to PET/CT (N=61) or PET/MRI (N=14) due to any aortic pathology in 2015-2017. The patients included those with abdominal aortic aneurysm (AAA) (N=48; 64%), aortitis (N=5; 6.7%), aortic dissection (N=4; 5.3%), patients undergoing EVAR (N=6; 8%), patients with excessive atherosclerosis (N=7; 9.3%), patients with concomitant AAA and retroperitoneal fibrosis (N=4; 5.3%) and patient with an intramural hematoma (N=1; 1.3%). The minimum follow-up period was 6 months (0.5-2.5 years). Clinical symptoms, aortic diameter, growth rate and CRP levels were analyzed during the follow-up and correlation with PET/CT or PET/MRI findings was evaluated. Increased metabolic activity in the aorta was found in 25 of the 75 examined patients (33.3%). Based on statistical analysis there were no associations between increased activity based on PET/CT or PET/MRI in the aortic wall and disease symptoms or progression. Our results provide no evidence that hybrid methods can predict further development of pathological findings in the abdominal aorta. PET/CT- or PET/MRI-based activity did not correlate with disease symptoms, AAA progression rate or dissection, either. Our results are also supported by some recent literature data.

Prior reports have associated increased circulating levels of matrix metalloproteinase-9 (MMP-9), an endopeptidase active in the extracellular matrix, with the formation and rupture of aortic aneurysms, raising the possibility that MMP-9 may be a useful diagnostic or therapeutic target for aortic pathology. However, associations between MMP-9 and pathological abdominal aortic phenotypes in the general population have not been reported. In the Dallas Heart Study, a population-based sample of Dallas County residents (n = 2304), we measured MMP-9 and performed magnetic resonance imaging (MRI) of the abdominal aorta, measuring aortic compliance, plaque, wall thickness and luminal diameter. After adjustment for traditional cardiac risk factors and body size, higher MMP-9 quartiles were independently associated with higher aortic wall thickness and larger luminal diameter (p < 0.0001 for each), but not abdominal aortic plaque (p = 0.08), coronary artery calcium (p = 0.20) or the aortic luminal diameter/aortic wall thickness ratio (p = 0.37), supporting the hypothesis that therapies targeting MMP-9 may affect the abdominal aortic wall and modify aortic pathology.

Endovascular treatment of acute and chronic aortic pathology in patients with Marfan syndrome

Coexisting multilevel aortic pathologies were caused by atherosclerosis and hypertension and presented in a small subgroup of patients. Endovascular repair is a safe and effective treatment for a variety of aortic pathologies. However, fewer small series and cases were reported using simultaneous thoracic endovascular repair (TEVAR) and endovascular aneurysm repair (EVAR) for both aortic segments. To determine the outcomes of simultaneous and separately TEVAR and EVAR treating for multilevel aortic pathologies. Between 2010 and 2020, 31 patients and 22 patients were treated by one-staged and two-staged repair, respectively at a single center. All patients had the concomitant thoracic and abdominal aortic disease (aortic dissection, aneurysms, and penetrating aortic ulcers). Compared with the patients with two-staged aortic repair, the one-staged repair patients were older (mean age, 68 vs. 57 years; P < 0.001) and had a larger preoperative maximal aortic diameter (67.03 ± 10.65 vs. 57.45 ± 10.36 mm; p = 0.002). The intraoperative and postoperative outcomes show that the procedure times and length of hospital stay (LOS) were longer in the two-staged group. There is no significant difference in postoperative complications between the two groups. In the follow up, the freedom from re–intervention and the mean survival rate for the one-staged group were 100 vs. 100%, 92.4 vs. 95%, and 88 vs. 88% at one, two, and 5 years, respectively, whereas the mean survival rate for the two-staged group was 86.4 vs. 90.5%, 87 vs. 90.5%, and 76 vs. 84% at one, two, and 5 years, respectively, all with no statistical difference. Combined TEVAR and EVAR can be performed successfully with minimal morbidity and mortality. The one-staged repair was not associated with the increased risk for multilevel aortic pathologies treatment.

Endovascular therapy for the management of aortic pathology in patients with degenerative connective tissue disorder (DCTD) is controversial. Current guidelines are based on a paucity of literature and registry data are lacking. This study reports on medium term outcomes of patients with diagnosed DCTD compared to those without DCTD who were included in the W.L. Gore Global Registry for Endovascular Aortic Treatment (GREAT). Patients included in the GREAT registry who underwent treatment for any thoracic or abdominal aortic pathology were included and grouped according to the presence or absence of a DCTD. Baseline demographic and procedural data were collected as well as data relating to key outcomes within 5 years follow-up, including all-cause mortality, aortic-related mortality, reinterventions and serious adverse events (SAE). Multivariable Cox proportional hazards models were built to determine if any association existed between the presence of DCTD and any key outcomes. The analysis included 92 (1.9%) with DCTD and 4741 (98.1%) without DCTD. Patients with DCTD were more likely to be female (34.8% vs. 18.5%, P < .0001) and younger (66.8 [15.1] vs. 71.7 [10.3] years, P=.013) than those without DCTD. They were also more likely to have had prior aortic intervention (22.8% vs. 13.9%, P=.015) and an associated branch vessel procedure with the index operation (30.3% vs. 18.6%, P=.005). The majority of reinterventions in both groups occurred within the first 2 years and multivariable models demonstrated that the presence of DCTD was not predictive of all-cause mortality, aortic-related mortality, reinterventions or SAE within 5 years. Within the limitations of registry data, this work demonstrates the medium term safety and durability of endovascular stent-grafts across a spectrum of aortic pathology in some patients with DCTD. More work is required to determine the applicability of these findings to specific sub-types of DCTD and aortic pathology.

Simultaneous Endovascular Repair for Thoracic and Abdominal Aortic Pathologies: Early and Midterm Results

Editors' commentary

Chronic as well as acute diseases of the thoracic aorta are attracting increasing attention, both in the light of an ageing Western and Oriental population and with the proliferation of modern diagnostic imaging modalities. While classic surgical strategies still dominate the treatment of pathology of the ascending aorta and the proximal arch region, new endovascular concepts are emerging and are likely to evolve as primary treatment strategies for descending and abdominal aortic pathology. Additionally, aortic arch pathologies are becoming the target of hybrid approaches combining surgical head-vessel debranching and interventional stent-graft implantation in an attempt to improve outcome by avoiding the high risk of open arch repair or complete replacement. Nonetheless, due to the complexity of the underlying vascular disease, each patient should be discussed in a team consisting of cardiologists, cardiac surgeons, and an imaging specialist in order to design an individualized therapeutic strategy carried out best in a center with experience in both endovascular and surgical procedures.