Editor's Choice - The VASCUNExplanT Project: An International Study Assessing Open Surgical Conversion of Failed Non-Infected Endovascular Aortic Aneurysm Repair.

OBJECTIVE: The need for open surgical conversion (OSC) after failed endovascular aortic aneurysm repair (EVAR) persists, despite expanding endovascular options for secondary intervention. The VASCUNExplanT project collected international data to identify risk factors for failed EVAR, as well as OSC outcomes. This retrospective cross sectional study analysed data after OSC for failed EVAR from the VASCUNET international collaboration. METHODS: VASCUNET queried registries from its 28 member countries, and 17 collaborated with data from patients who underwent OSC (2005 - 2020). Any OSC for infection was excluded. Data included demographics, EVAR, and OSC procedural details, as well as post-operative mortality and complication rates. RESULTS: There were 348 OSC patients from 17 centres, of whom 33 (9.4%) were women. There were 130 (37.4%) devices originally deployed outside of instructions for use. The most common indication for OSC was endoleak (n = 143, 41.1%); ruptures accounted for 17.2% of cases. The median time from EVAR to OSC was 48.6 months [IQR 29.7, 71.6]; median abdominal aortic aneurysm diameter at OSC was 70.5 mm [IQR 61, 82]. A total of 160 (45.6%) patients underwent one or more re-interventions prior to OSC, while 63 patients (18.1%) underwent more than one re-intervention (range 1 - 5). Overall, the 30 day mortality rate post-OSC was 11.8% (n = 41), 11.1% for men and 18.2% for women (p = .23). The 30 day mortality rate was 6.1% for elective cases, and 28.3% for ruptures (p < .0001). The predicted 90 day survival for the entire cohort was 88.3% (95% CI 84.3 - 91.3). Multivariable analysis revealed rupture (OR 4.23; 95% CI 2.05 - 8.75; p < .0001) and total graft explantation (OR 2.10; 95% CI 1.02 - 4.34; p = .04) as the only statistically significant predictive factors for 30 day death. CONCLUSION: This multicentre analysis of patients who underwent OSC shows that, despite varying case mix and operative techniques, OSC is feasible but associated with significant morbidity and mortality rates, particularly when performed for rupture.

Contemporary management and outcomes of peripheral venous aneurysms: A multi-institutional study.

OBJECTIVE: Extremity venous aneurysms result in the risk of pulmonary embolism (PE) and chronic venous insufficiency. At present, owing to the rarity of these aneurysms, no consensus for their treatment has been established. The purpose of the present study was to review the presentation, natural history, and contemporary management of extremity venous aneurysms. METHODS: We performed a retrospective, multi-institutional review of all patients with extremity venous aneurysms treated from 2008 to 2018. A venous aneurysm was defined as saccular or fusiform with an aneurysm/vein ratio of >1.5. RESULTS: A total of 66 extremity aneurysms from 11 institutions were analyzed, 40 of which were in a popliteal location, 14 iliofemoral, and 12 in an upper extremity or a jugular location. The median follow-up was 27 months (range, 0-120 months). Of the 40 popliteal venous aneurysms, 8 (20%) had presented with deep vein thrombosis (DVT) or PE, 13 (33%) had presented with pain, and 19 had been discovered incidentally. The mean size of the popliteal venous aneurysms presenting with DVT or PE was larger than that of those presenting without thromboembolism (3.8 cm vs 2.5 cm; P = .003). Saccular aneurysm morphology in the lower extremity was associated with thromboembolism (30% vs 9%; P = .046) and fusiform aneurysm morphology with a thrombus burden >25% (45% vs 3%). Patients presenting with thromboembolism were more likely to have had a thrombus burden >25% in their lower extremity venous aneurysm compared with those who had presented without thromboembolism (70% vs 9%). Approximately half of all the patients underwent immediate intervention, and half were managed with observation or antithrombotic regimen. In the non-operative cohort, three patients subsequently developed a DVT. Eight patients in the medically managed cohort went on to require surgical intervention. Of the 12 upper extremity venous aneurysms, none had presented with DVT or PE, and only 2 (17%) had presented with pain. Of the 66 patients in the entire cohort, 41 underwent surgical intervention. The most common indication was the absolute aneurysm size. Nine patients had undergone surgery because of a DVT or PE, and 11 for pain or extremity swelling. The most common surgery was aneurysmorrhaphy in 21 patients (53%), followed by excision and ligation in 14 patients (35%). Five patients (12%) had undergone interposition bypass grafting. A postoperative hematoma requiring reintervention was the most common complication, occurring in three popliteal vein repairs and one iliofemoral vein repair. None of the patients, treated either surgically or medically, had reported post-thrombotic complications during the follow-up period. CONCLUSIONS: Large lower extremity venous aneurysms and saccular aneurysms with thrombus >25% of the lumen are more likely to present with thromboembolic complications. Surgical intervention for lower extremity venous aneurysms is indicated to reduce the risk of venous thromboembolism (VTE) and the need for continued anticoagulation. Popliteal aneurysms >2.5 cm and all iliofemoral aneurysms should be considered for repair. Upper extremity aneurysms do not have a significant risk of VTE and warrant treatment primarily for symptoms other than VTE.

The role of tissue remodeling in mechanics and pathogenesis of abdominal aortic aneurysms.

Arterial walls can be regarded as composite materials consisting of collagen fibers embedded in an elastic matrix and smooth muscle cells. Remodeling of the structural proteins has been shown to play a significant role in the mechanical behavior of walls during pathogenesis of abdominal aortic aneurysms (AAA). In this study, we systematically studied the change in the microstructure, histology and mechanics to link them to AAA disease progression. We performed biaxial extension tests, second-harmonic generation imaging and histology on 15 samples from the anterior part of AAA walls harvested during open aneurysm surgery. Structural data were gained by fitting to a bivariate von Mises distribution and yielded the mean fiber direction and in- and out-of-plane fiber dispersions of collagen. Mechanical and structural data were fitted to a recently proposed material model. Additionally, the mechanical data were used to derive collagen recruitment points in the obtained stress-stretch curves. We derived 14 parameters from histology such as smooth muscle cell-, elastin-, and abluminal adipocyte content. In total, 22 parameters were obtained and statistically evaluated. Based on the collagen recruitment points we were able to define three different stages of disease progression. Significant differences in elastin content, collagen orientation and adipocyte contents were discovered. Nerves entrapped inside AAA walls pointed towards a significant deposition of newly formed collagen abluminally, which we propose as neo-adventitia formation. We were able to discriminate two types of remodeled walls with a high collagen content - potentially safe and possibly vulnerable walls with a high adipocyte content inside the wall and significant amounts of inflammation. The study yielded a hypothesis for disease progression, derived from the systematic comparison of mechanical, microstructural and histological changes in AAAs. STATEMENT OF SIGNIFICANCE: Remodeling of the structural proteins plays an important role in the mechanical behavior of walls during pathogenesis of abdominal aortic aneurysms (AAA). We analyzed changes in the microstructure, histology and biomechanics of 15 samples from the anterior part of AAA walls and, for the first time, linked the results to three different stages of disease progression. We identified significant differences in elastin content, collagen orientation, adipocyte contents, and also a deposition of newly formed collagen forming a neoadventitia. We could discriminate two types of remodeled walls: (i) potentially safe and (ii) possibly vulnerable associated with inflammation and a high amount of adipocytes.

Increased hospital costs are associated with low skeletal muscle mass in patients undergoing elective open aortic surgery.

OBJECTIVE: Low psoas muscle area is shown to be an indicator for worse postoperative outcome in patients undergoing vascular surgical. Additionally, it has been associated with longer durations of hospital stay in patients with cancer who undergo surgery and subsequently greater health care costs in Europe and the United States. We sought to evaluate this effect on hospital expenditure for patients undergoing vascular repair in a health care system with universal access. METHODS: Skeletal muscle mass was assessed on preoperative abdominal computed tomography scans of patients undergoing open aortic aneurysm repair in a retrospective fashion. The skeletal muscle index (SMI) was used to define low muscle mass. Health care costs were obtained for all patients and the relationship between a low SMI and higher costs was explored using linear regression and cross-sectional analysis. RESULTS: We included 156 patients (81.5% male) with a median age of 72 years undergoing elective surgery for infrarenal abdominal aortic aneurysm in this analysis. The median SMI for patients with low skeletal muscle mass was 53.21 cm2/kg and for patients without, 70.07 cm2/kg. Hospital duration of stay was 2 days longer in patients with low skeletal muscle mass as compared with patients with normal (14 days vs 11 days; P = .001), as was duration of intensive care stay (3 days vs 1 day; P = .01). The median overall hospital costs were €10,460 higher for patients with a low SMI as compared with patients with a normal physical constitution (€53,739 [interquartile range, €45,007-€62,471] vs €43,279 [interquartile range, €39,509-€47,049]; P = .001). After confounder adjustment, a low SMI was associated with a 14.68% cost increase in overall hospital costs, for a cost increase of €6521. CONCLUSIONS: Low skeletal muscle mass is independently associated with higher hospital as well as intensive care costs in patients undergoing elective aortic aneurysm repair. Strategies to reduce this risk factor are warranted for these patients.

Mechanical response of human subclavian and iliac arteries to extension, inflation and torsion.

Peripheral vascular trauma due to injuries of the upper and lower limbs are life-threatening, and their treatment require rapid diagnosis and highly-qualified surgical procedures. Experienced surgeons have recognized that subclavian arteries, affected by injuries of the upper limbs, require a more careful handling due to fragility than common iliac arteries, which are may be affected by injures of the lower limbs. We investigated these two artery types with comparable diameter to evaluate the differences in the biomechanical properties between subclavian and iliac arteries. Human subclavian and common iliac arteries of 14 donors either from the right or the left side (age: 63 yrs, SD: 19,9 female and 5 male) were investigated. Extension-inflation-torsion experiments at different axial strains (0-20%), transmural pressures (0-200 mmHg) and torsion (±25°) on preconditioned arterial tubes were performed. Residual stresses in both circumferential and axial direction were determined. Additionally, the microstructure of the tissues was determined via second-harmonic generation imaging and by histological investigations. At physiological conditions (pi=13.3 kPa, λz=1.1) common iliac arteries revealed higher Cauchy stresses in circumferential and axial directions but a more compliant response in the circumferential direction than subclavian arteries. Both arteries showed distinct stiffer behavior in circumferential than in axial direction. Circumferential stiffness of common iliac arteries at physiological conditions increased significantly with aging (r=-0.67,p=0.02). The median inversion stretches, where the axial force is basically independent of the transmural pressure, were determined to be 1.05 for subclavian arteries and 1.11 for common iliac arteries. Both arteries exhibited increased torsional stiffness, when either axial prestretch or inflation pressure was increased. Residual stresses in the circumferential direction were significantly lower for subclavian arteries than for common iliac arteries at measurements after 30 min (p=0.05) and 16hrs (p=0.01). Investigations of the collagen microstructure revealed different collagen fiber orientations and dispersions in subclavian and iliac arteries. The difference in the collagen microstructure revealed further that the adventitia seems to contribute significantly to the passive mechanical response of the tested arteries at physiological loadings. Histological investigations indicated pronounced thickened intimal layers in subclavian and common iliac arteries, with a thickness comparable to the adventitial layer. In conclusion, we obtained biomechanical differences between subclavian and common iliac arteries, which possibly resulted from their different mechanical loadings/environments and respective in vivo movements caused by their anatomical locations. The biomechanical differences explored in this study are well reflected by the microstructure of the collagen and the histology of the investigated arteries, and the results can improve trauma patient care and endovascular implant design. STATEMENT OF SIGNIFICANCE: During surgical interventions surgeons experienced that subclavian arteries (SAs) supplying the upper extremities, appear more fragile and prone to damage during surgical repair than common iliac arteries (CIAs), supplying the lower extremities. To investigate this difference in a systematic way the aim of this study was to compare the biomechanical properties of these two arteries from the same donors in terms of geometry, extension-inflation-torsion behavior, residual stresses, microstructure, and histology. In regard to cardiovascular medicine the material behavior of aged human arteries is of crucial interest. Moreover, the investigation of SA is important as it can help to improve surgical procedures at this challenging location. Over the long-term it might well be of value in the construction of artificial arteries for substituting native arteries. In addition, the analysis of mechanical stresses can improve design and material choice for endovascular implants to optimize long-term implant function.

Microstructure and mechanics of healthy and aneurysmatic abdominal aortas: experimental analysis and modelling.

Soft biological tissues such as aortic walls can be viewed as fibrous composites assembled by a ground matrix and embedded families of collagen fibres. Changes in the structural components of aortic walls such as the ground matrix and the embedded families of collagen fibres have been shown to play a significant role in the pathogenesis of aortic degeneration. Hence, there is a need to develop a deeper understanding of the microstructure and the related mechanics of aortic walls. In this study, tissue samples from 17 human abdominal aortas (AA) and from 11 abdominal aortic aneurysms (AAA) are systematically analysed and compared with respect to their structural and mechanical differences. The collagen microstructure is examined by analysing data from second-harmonic generation imaging after optical clearing. Samples from the intact AA wall, their individual layers and the AAA wall are mechanically investigated using biaxial stretching tests. A bivariate von Mises distribution was used to represent the continuous fibre dispersion throughout the entire thickness, and to provide two independent dispersion parameters to be used in a recently proposed material model. Remarkable differences were found between healthy and diseased tissues. The out-of-plane dispersion was significantly higher in AAA when compared with AA tissues, and with the exception of one AAA sample, the characteristic wall structure, as visible in healthy AAs with three distinct layers, could not be identified in AAA samples. The collagen fibres in the abluminal layer of AAAs lost their waviness and exhibited rather straight and thick struts of collagen. A novel set of three structural and three material parameters is provided. With the structural parameters fixed, the material model was fitted to the mechanical experimental data, giving a very satisfying fit although there are only three material parameters involved. The results highlight the need to incorporate the structural differences into finite-element simulations as otherwise simulations of AAA tissues might not be good predictors for the actual in vivo stress state.

Phenotypical plasticity of vascular smooth muscle cells-effect of in vitro and in vivo shear stress for tissue engineering of blood vessels.

Vascular smooth muscle cells (vSMCs) can switch between a contractile (differentiated) and a synthetic (dedifferentiated) phenotype. Synthetic, proliferative vSMCs are observed during embryogenesis, wound repair, and tissue engineering. The potential of isolated vSMCs to reverse this phenotypic modulation depends strictly on culture conditions. Previous studies have demonstrated that applied shear stress is an important signal for vSMC phenotype. The objective of this study was to determine whether applied shear stress is capable of triggering re-differentiation of vSMCs in tissue-engineered aortas. vSMCs were isolated from ovine arteries. Cells were cultured statically or exposed to two- (2D) and three-dimensional (3D) shear stress after seeding on a tubular matrix. For 3D in vivo testing, grafts were seeded additionally with endothelial cells and implanted in the descending aorta. Particular attention was paid to the expression pattern of vSMC markers, cell ultra-structure, matrix remodeling activity, and proliferative activity. Cultured vSMCs de-differentiated during static in vitro culture, but 2D and 3D in vitro shear stress promoted re-expression of vSMC markers. During in vivo culture, vSMCs progressed toward a fully differentiated phenotype. Cells were expressing markers of differentiated vSMCs and resembled a morphologically contractile vSMC phenotype. Matrix remodeling activity and proliferative activity decreased. This study demonstrates the phenotypic plasticity of vSMCs and their ability to return to a differentiated phenotype under shear stress conditions. These results are crucial for tissue engineering of blood vessels, because they indicate for the first time the in vitro potential to regain physiological functionality of isolated vSMCs.

Tissue engineering of aortic tissue: dire consequence of suboptimal elastic fiber synthesis in vivo.

OBJECTIVE: To study autologous tissue engineered blood vessels (TEBV) in the descending aorta of juvenile sheep. METHODS: Autologous vascular smooth muscle cells (vSMC) and endothelial cells were obtained from ovine carotid arteries. vSMC were seeded on bioresorbable scaffolds and dynamically cultured for 14 days. Following endothelialization an additional external ovine small intestinal submucosa wrapping was applied. Constructs were implanted in the descending aorta of juvenile sheep and removed after 1, 3, 6, 12 and 24 weeks for evaluation with histological, microscopical and biochemical techniques. RESULTS: Up to 3 months after implantation, grafts were fully patent, without any signs of dilatation, occlusion or intimal thickening. Scanning electron microscopy revealed a confluent luminal endothelial cell layer. In contrast, the 6 months graft displayed significant dilatation and partial thrombus formation. Histology displayed layered tissue formation resembling native aorta. Extracellular matrix (ECM) stains, immunostaining and Transmission Electron Microscopy (TEM) revealed alternating layers of vSMC and extracellular matrix consisting of collagen, elastin and glycosaminogycans. Compared to native aorta, the elastin content of the TE grafts was significantly reduced. CONCLUSION: In this study, we report for the first time, the implantation of a TEBV in the descending aorta in a large animal model. TEBV were fully functional for up to 3 months. At 6 months the graft remained functional but significantly dilated, most likely caused by an insufficient elastic fiber synthesis. Hence, future studies need to focus on the stimulation of elastin synthesis in TEBV.

Recurrent vertebral arteriovenous fistula after surgical repair: treatment with a self-expanding stent-graft.

PURPOSE: To describe successful endovascular repair of a recurrent vertebral arteriovenous fistula (AVF) after surgical correction. CASE REPORT: A 42-year-old woman presented with recurrent dizziness, nausea, and headaches. A loud bruit in the right neck was present. Central venous catheter insertion had been done 1 year previously, creating an angiographically documented right-sided vertebral AVF that was successfully excluded by a surgical procedure. Four weeks later, the AVF reappeared. Successful endovascular repair with a self-expanding stent-graft was performed. Follow-up over 12 months was uneventful, with a patent vertebral artery and no recurrence of symptoms. CONCLUSIONS: Endovascular stent-graft repair is feasible and offers a therapeutic alternative in the treatment of vertebral AVF, in particular for recurrence after initial surgery. This minimally invasive method may become the treatment of choice in the management of such lesions, preserving patency of the vertebral artery.

Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis.

Oxidation products of low-density lipoproteins have been suggested to promote inflammation during atherogenesis, and reticulocyte-type 15-lipoxygenase has been implicated to mediate this oxidation. In addition, the 5-lipoxygenase cascade leads to formation of leukotrienes, which exhibit strong proinflammatory activities in cardiovascular tissues. Here, we studied both lipoxygenase pathways in human atherosclerosis. The 5-lipoxygenase pathway was abundantly expressed in arterial walls of patients afflicted with various lesion stages of atherosclerosis of the aorta and of coronary and carotid arteries. 5-lipoxygenase localized to macrophages, dendritic cells, foam cells, mast cells, and neutrophilic granulocytes, and the number of 5-lipoxygenase expressing cells markedly increased in advanced lesions. By contrast, reticulocyte-type 15-lipoxygenase was expressed at levels that were several orders of magnitude lower than 5-lipoxygenase in both normal and diseased arteries, and its expression could not be related to lesion pathology. Our data support a model of atherogenesis in which 5-lipoxygenase cascade-dependent inflammatory circuits consisting of several leukocyte lineages and arterial wall cells evolve within the blood vessel wall during critical stages of lesion development. They raise the possibility that antileukotriene drugs may be an effective treatment regimen in late-stage disease.

Revascularization during acute myocardial infarction: risks and benefits revisited.

BACKGROUND: Indication for immediate revascularization during acute myocardial infarction (MI) is debated. Drug-resistant crescendo angina, as well as hemodynamic compromise, however, often requires acute operation. In this study the differential risks of acute coronary artery bypass grafting with and without MI were stratified. METHODS: Five hundred eighteen patients undergoing isolated coronary artery bypass grafting were investigated. Thirty-nine patients underwent acute revascularization because of enzyme-proven or electrocardiogram-proven MI accompanied by crescendo angina, hemodynamic compromise, or both. They were compared with 33 emergent, 63 urgent, and 383 elective patients without MI. Preoperative risk factors for early mortality and necessity of continuous venovenous hemofiltration were analyzed by means of logistical regression analysis. Perioperative data were compared. RESULTS: Early mortality of the MI cohort was 15.4%, in contrast to 15.2% in emergent, none in urgent, and 2.1% in elective patients. Left internal thoracic artery was used in 87% of MI, 97% of emergent, 94% of urgent, and 97% of elective patients. Intraaortic balloon pump was necessary in 50% of MI patients, 27% of emergent, 6.3% of urgent, and 3.1% of elective cases. Continuous venovenous hemofiltration was performed in 29% of MI patients, 15% of emergent, 4.9% of urgent, and 3.4% of elective patients. Hemodynamic instability significantly increased the odds ratio for early mortality and continuous venovenous hemofiltration. CONCLUSIONS: Patients undergoing acute revascularization carried an elevated risk to die early notwithstanding the presence or absence of acute MI. Liberal use of left internal thoracic artery grafts was not detrimental in acute patients whereas liberal use of intraaortic balloon pump was beneficial. In almost 30% of MI patients, continuous venovenous hemofiltration was not necessary, implying a severely impaired perioperative hemodynamic condition. Immediate revascularization in the presence of acute MI is therefore indicated although it may be addressed as a separate high-risk group.