Safety and Validity of the Proposed European Society for Vascular Surgery Infrarenal Endovascular Aneurysm Repair Surveillance Protocol: A Single Centre Evaluation.

OBJECTIVE: Long term surveillance after endovascular aneurysm repair (EVAR) is essential to detect late complications, but there is variation in practice. The European Society for Vascular Surgery (ESVS) made a recommendation for a new surveillance protocol; one element involves risk stratifying patients depending on sac size reduction and presence of endoleak at their 30 day computed tomography angiogram into low risk groups (delayed imaging to five years) or higher risk groups (continue with the current protocol). The aim was to test this suggested protocol retrospectively within an EVAR patient cohort. METHODS: Data on EVARs performed from October 2009 to October 2019 were collected. Information gathered from an existing surveillance programme was used to assess the proposed ESVS protocol. All patients who underwent re-intervention were reviewed to see whether adopting the proposed ESVS protocol would have detected these events. RESULTS: In total, 309 procedures were included. Altogether, 219 of these patients had no endoleak (70.9%) and 86 had a type II (27.8%) endoleak. Only four developed a type I or III endoleak. No patient in the low risk cohort (no initial endoleak or sac shrinkage > 1 cm) required secondary intervention. Five year follow up data were available for 103 patients. In the type II endoleak group, there were 28 secondary interventions in 22 patients. No patient experienced a ruptured aneurysm within five years post-operatively. Had the proposed ESVS protocol been followed, all patients requiring a secondary intervention or with increasing sac size would have been detected/captured. Further, adherence to the ESVS guidelines would have resulted in 103 patients with a five year follow up history qualifying for reduced surveillance. A further 120 patients who had reached the three and four year follow up timepoints could have qualified for a reduced surveillance, reducing imaging cost further. CONCLUSION: Adopting the proposed ESVS EVAR surveillance protocol safely identified "low risk" patients who did not go on to require a secondary intervention. These patients could benefit from reduced surveillance scanning.

Quality of life of patients with peripheral arterial disease and chronic stable angina.

The Coronary Artery Disease in gENeral practiCE (CADENCE) study examined chronic stable angina (CSA). This further analysis examined atherosclerotic risk factors, symptomatic status, clinical management, and quality of life in patients with CSA with and without peripheral arterial disease (PAD). The CADENCE study involved 207 Australian general practitioners (GPs) recruiting 10 to 15 consecutively presenting patients with CSA (n = 2031). General practitioners completed a 2-page case report form, detailing demographic data, cardiovascular status, risk factors, and GP perception of control. Patients completed the Seattle Angina Questionnaire. Patients with coexisting CSA and PAD (17%) were more likely to be older and had more comorbidities than patients with CSA without coexisting PAD. Patients with peripheral arterial disease had a longer history of heart disease and were more likely to experience angina on a weekly basis. Patients with peripheral arterial disease had poorer quality-of-life indices.

Blood leucocyte telomere DNA content predicts vascular telomere DNA content in humans with and without vascular disease.

AIMS: Previous studies have suggested that reduced telomere length in circulating leucocytes in humans is associated with premature vascular disease and by implication, accelerated vascular ageing. Importantly, a link between telomere length in circulating leucocytes and the blood vessel wall has never been established. We, thus, investigated the relationship between vascular wall and circulating leucocyte telomere length in humans with and without overt vascular disease. METHODS AND RESULTS: Aortic biopsies and paired blood leucocytes were obtained from 20 patients with asymptomatic abdominal aortic aneurysms (AAAs), undergoing elective open repair, and 12 morphologically normal aortas from a group of cadaveric organ donors of similar mean age. Telomere content was compared by quantitative PCR and expressed as telomere:genomic DNA ratio. The telomere:genomic DNA content was significantly reduced in wall biopsies of AAA vs. normal aorta, and this difference remained after adjusting for age and gender. There were strong correlations between leucocyte and vascular telomere content when the AAA and control groups were analysed either separately or grouped irrespective of the presence of vascular disease (r = 0.62, P < 0.001). CONCLUSION: The findings demonstrate that leucocyte DNA content is predictive of vascular telomere content and is an accurate surrogate for human vascular age.

Plasma matrix metalloproteinase levels do not predict tissue levels in abdominal aortic aneurysms suitable for elective repair.

The role of matrix metalloproteinases (MMPs) in abdominal aortic aneurysm (AAA) pathogenesis is well described. However, a clear role for the MMPs in disease prediction has not been established. The aim of this study was to determine if circulating levels of MMPs correlated with AAA diameter and with MMP concentrations within the aneurysm wall. Preoperative plasma samples and intraoperative infrarenal AAA sac biopsies were taken in a standard fashion from 31 patients undergoing elective repair.The concentrations of MMP-1, MMP-2, MMP-3, MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1, and TIMP-2 were quantified in plasma and aneurysm wall homogenates using enzyme-linked immunosorbent assay. Comparison used the Spearman correlation. There were no correlations between the paired plasma and aneurysm wall concentrations for any MMP or TIMP. Correlation between MMP-9 levels in the aneurysm wall and aneurysm diameter was negative (r = -.42, p = .019). Other correlations between plasma and tissue levels with aneurysm diameter were nonsignificant.

Abdominal aortic aneurysm rupture is associated with increased medial neovascularization and overexpression of proangiogenic cytokines.

OBJECTIVE: Matrix metalloproteinase (MMP) activity has been linked to abdominal aortic aneurysm (AAA) rupture. Medial neovascularization (MNV), a histopathologic characteristic of AAAs, involves proteolytic degradation of extracellular matrix by MMPs to facilitate endothelial cell migration. The role of MNV in aneurysm rupture is unknown. This study investigated whether MNV is increased in aneurysm rupture. METHODS AND RESULTS: Biopsy samples from aneurysm rupture edge were compared with control biopsy samples from aneurysm wall at the level of rupture and from anterior sac in 12 ruptured AAAs. Further controls were obtained from anterior sac of 10 nonruptured AAAs. MNV, microvessel diameter, maturity index, and inflammatory infiltrate were quantified using morphometric analyses following immunohistochemistry. Expression of proangiogenic mediators was quantified using quantitative real-time-polymerase chain reaction. Compared with anterior sac and aneurysm wall at level of rupture, MNV was increased (P<0.001) in rupture edge biopsy samples and consisted of smaller diameter (P<0.001) and more immature microvessels (P<0.001). mRNA expression of alpha(v)-integrin, vascular endothelial growth factor, vascular endothelial-cadherin, monocyte chemoattractant protein-1, and vimentin was increased (P<0.05) in rupture edge biopsy samples. CONCLUSIONS: This study demonstrated increased medial neovascularization and overexpression of proangiogenic cytokines at aneurysm rupture edge. Further investigations into whether this angiogenic response was a causative factor of aneurysm rupture are needed.

Matrix metalloproteinase-8 and -9 are increased at the site of abdominal aortic aneurysm rupture.

BACKGROUND: Abdominal aortic aneurysm (AAA) expansion is characterized by extracellular matrix degradation and widespread inflammation. In contrast, the processes that characterize AAA rupture are not well understood. The aim of this study was to investigate the proteolytic and cellular activity of ruptured AAA, focusing on matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). METHODS AND RESULTS: Anterior aneurysm wall biopsies were taken from 55 nonruptured and 21 ruptured AAAs. A further biopsy from the site of rupture was taken from 12 of the ruptured AAAs. MMP-1, -2, -3, -8, -9, and -13, as well as TIMP-1 and -2, were quantified in each biopsy with ELISA. A comparison of anterior aneurysm biopsies showed no difference in MMP or TIMP concentrations between nonruptured and ruptured AAA. In a comparison of ruptured AAA biopsies, MMP-8 and -9 levels were significantly elevated in the 12 rupture site biopsies compared with their 12 paired anterior wall biopsies, whereas other MMPs and TIMPs showed no difference (MMP-8, P<0.001; MMP-9, P=0.01). MMP-8 and -9 expression was mediated by native mesenchymal cells and was independent of the inflammatory infiltrate. CONCLUSIONS: A localized increase in MMP-8 and -9, mediated by native mesenchymal cells, presents a potential pathway for collagen breakdown and AAA rupture.

Suitability of ruptured AAA for endovascular repair.

PURPOSE: To determine the anatomical suitability and the range of endografts required to undertake an endovascular repair (EVR) program for ruptured abdominal aortic aneurysms. METHODS: The morphology of ruptured and nonruptured AAAs were compared by retrospective review of computed tomographic scans from 51 patients (47 men; mean age 76 years, range 55-90) with ruptured AAAs and 50 patients (37 men; mean age 74 years, range 57-75) with nonruptured AAAs. Three experienced clinicians reviewed the scans for EVR suitability based on a generic trimodular endograft with suprarenal fixation. Endograft oversizing was assumed to be 10% to 20%. RESULTS: Interobserver agreement was high, with a mean kappa of 0.78 (range 0.75-0.83, p<0.001). In all, 41% of ruptured and 68% of nonruptured AAAs were suitable for EVR (p=0.009). Ruptured AAAs had shorter mean neck lengths (17+/-12 versus 22+/-11 mm, p=0.031) and larger mean aneurysm diameters (75+/-15 versus 63+/-9 mm, p>0.001). Neck length and neck diameter were significantly correlated for ruptured AAAs (r=-0.34, p=0.018). The main contraindication to EVR was hostile neck morphology. A range of endografts with aortic components from 24 to 32 mm and iliac components from 12 to 22 mm would be required to stent 41% of ruptured AAAs. CONCLUSIONS: Ruptured AAAs are less suitable for EVR due to differing neck morphology. An EVR program for ruptured AAA requires an inventory of endografts with appropriate aortic and iliac components.