Changes in platelet function with inflammation in patients undergoing vascular surgery.

The role of platelets in ischaemic events is well established. Aspirin represents the default antiplatelet and blocks the metabolism of arachidonic acid (AA) at the cyclo-oxygenase enzyme (COX). AA is commonly used as a test of response to aspirin, but recent data raise uncertainty about the validity of this approach. Specifically, in some patients AA-induced clotting is not suppressed, but the level of COX-dependent AA metabolite, thromboxane B2 (TXB2) is negligible. Furthermore, AA-induced whole blood clotting varies dynamically in individuals, who are aspirin responsive according to TXB2 levels. The aim of this study was to assess the level of AA-, ADP- and thrombin-mediated platelet reactivity in patients on aspirin before, during, and after major vascular surgery, which represents a model of on/off vascular inflammation. Firstly, we hypothesized, that in association with this inflammatory episode AA-, ADP- and thrombin-induced clotting would change in a dynamic manner. Secondly, that AA-induced clotting will be modified despite complete suppression of platelet TXB2 production by aspirin throughout the periprocedural period, possibly via a lipoxygenase-mediated mechanism. Fourty patients underwent major vascular surgery (open abdominal aortic aneurysm operation, infrainguinal bypass for subcritical limb ischaemia or peripheral aneurysm repair with bypass). They were all on 75 mg of aspirin prior to and throughout the perioperative period and received 5000 units of unfractionated heparin intraoperatively. AA-, ADP-, and thrombin-induced clotting, AA metabolites (TXB2 and 12-Hyroxyeicosatetraenoic acid (12-HETE)) and inflammatory markers (CRP, IL-6, TNF-α and CD40) were measured pre-procedure and at 2, 24, 48 hours, 3 to 5 days and 3 months after surgery. AA-, ADP- and thrombin-induced platelet reactivity was assessed using thrombelastography. TXB2, 12-HETE, IL-6, TNF-α, CD40 were determined using the sequential competitive binding Enzyme-Linked ImmunoAssay technique and CRP was determined using an immune-turbidimetric test on human serum. There was a transient rise in inflammatory markers in the early perioperative period (CRP at 24, 48 hours and 3 to 5 days p < 0.001 and IL-6 at 2, 24, 48 hours and 3 to 5 days p < 0.001 as compared to baseline). Patients had negligible levels of TXB2 throughout, confirming a consistent therapeutic response to aspirin. There was a transient rise in thrombin-mediated clotting (MAThrombin at 48 hours p = 0.001 and 3 to 5 days p < 0.001) and a fall in AA- and ADP-induced clotting in the early post op period (both MAAA and MAADP p = 0.001 at 2 hours). At 3 months, the level of AA- and ADP-induced clotting was significantly higher than at baseline (p = 0.008 for MAAA and p = 0.002 for MAADP), hence demonstrating a rebound effect. These data demonstrate a novel dynamic variation in platelet aggregation with acute vascular inflammation, including AA-induced whole blood clotting which is apparently COX-1 independent.

Understanding Patient Acceptance of Risk with Treatment Options for Intermittent Claudication.

BACKGROUND: Intermittent claudication has a major impact on the quality of life and functional ability of the patient. However, when treating these patients, management is largely influenced by vascular surgeons' perceptions of risk. There is little information available regarding the level of risk that patients perceive to be acceptable, when considering complications of treatment. This study investigates patients' acceptance of risk associated with current management options for intermittent claudication and explores factors associated with greater risk acceptance. METHODS: Patients with confirmed intermittent claudication presenting to vascular clinic and supervised exercise classes were surveyed in a single-center prospective study. A standard gamble-type method was used to measure patients' acceptance of risk associated with medical treatment, angioplasty, and surgical bypass. Level of risk acceptance was correlated to patient factors. RESULTS: Fifty patients were surveyed; 74% were male, median age was 68 years (interquartile range [IQR] 59-74), maximal walking distance was 100 m (IQR 70-200), and ankle-brachial pressure index was 0.65 (IQR 0.60-0.78). Median risk acceptance for treatment failure was 70% for medical treatment, 50% for angioplasty, and 40% for surgical bypass. Median risk acceptance for major amputation and death was 0% for all 3 management options. Claudicants with maximal walking distance <100 m accepted higher risk of treatment failure (P = 0.0005 for medical treatment, P = 0.0038 for angioplasty), and death with medical treatment (P = 0.0009). There was no significance between claudication distance and risk acceptance of major amputation with any treatment modality or death with angioplasty or surgical bypass. There was no significant correlation among level of risk acceptance and age, gender, or diabetic status. CONCLUSIONS: Claudicants are prepared to accept significant risk of treatment failure, in order to gain benefit, but regardless of claudication distance, patients have low acceptance of the risk of amputation or death. Patient acceptance of risk should be considered when planning management.

Emergency revascularisation in a patient with acute mesenteric ischaemia: the role of open revascularisation and compensatory blood flow.

PURPOSE: This case highlights the importance of timely diagnosis and management of acute mesenteric ischaemia and illustrates the compensatory mechanisms of the mesenteric vasculature. CASE REPORT: A 53-year-old female presented with fever, abdominal pain, and vomiting. The patient had no risk factors for atherosclerosis and was a non-smoker in sinus rhythm with no history of coagulopathy. She was initially treated for viral gastroenteritis. Due to lack of clinical improvement and a rising C-Reactive Protein (416), a CT scan was performed. This demonstrated small bowel ischaemia, chronic occlusion of the coeliac axis, and a long acute-on-chronic occlusion of the superior mesenteric artery (SMA). The length and morphology of the SMA occlusion precluded endovascular treatment. Emergency laparotomy demonstrated 1 m of necrotic small bowel and a pulseless mesentery. An aorto-SMA bypass, using good-quality long saphenous vein was performed, with segmental small bowel resection. Postoperative nutritional support was required with discharge on the 23rd post-operative day. Interval surveillance confirmed graft patency. One year post-discharge, she presented to routine clinic with paroxysmal right iliac fossa pain and decreased appetite. CT angiography showed a long tight 75% stenosis of the graft and she was admitted for mesenteric angioplasty. Angiography confirmed a significantly hypertrophied inferior mesenteric artery, which was now the dominant mesenteric supply. CONCLUSIONS: This case demonstrates the importance of emergency mesenteric revascularisation and how it acts as a bridge to anatomical compensation, allowing the collateral circulation to develop and the IMA to hypertrophy, becoming the dominant mesenteric supply.

A prospective double-blind randomized controlled trial of radiofrequency versus laser treatment of the great saphenous vein in patients with varicose veins.

BACKGROUND: Endovenous ablation of varicose veins using radiofrequency ablation (RFA) and endovenous laser therapy (EVLT) has reported advantages over traditional open surgical treatment. There is little evidence comparing the efficacy and patient-reported outcomes between the 2 endovenous solutions. This study compares the RFA and EVLT strategies in a prospective double-blind clinical trial. METHODS: Consecutive patients with primary unilateral great saphenous vein (GSV) reflux undergoing endovenous treatment were randomized to RFA (VNUS ClosureFAST) or EVLT (810-nm diode laser). The primary outcome measure was GSV occlusion at 3 months after treatment. Secondary outcome measures were occlusion at 7 days, postoperative pain, analgesic requirement, and bruising, assessed at day 7 after surgery. Quality of life (QoL) was assessed preoperatively and 3 months after surgery using the Aberdeen Varicose Vein Questionnaire (AVVQ) and EQ-5D. RESULTS: A total of 159 patients were randomized to RFA (79 patients) or EVLT (80 patients). Groups were well matched for demographics, disease extent, severity, and preoperative QoL. Duplex scanning confirmed 100% vein occlusion at 1 week in both groups. At 3 months, occlusion was 97% for RFA and 96% for EVLT; P = 0.67. Median (interquartile range) percentage above-knee bruise area was greater after EVLT 3.85% (6.1) than after RFA 0.6% (2); P = 0.0001. Postoperative pain assessed at each of the first 7 postoperative days was less after RFA (P = 0.001). Changes in the AVVQ (P = 0.12) and EQ-5D (P = 0.66) at 3 months were similar in both groups. CONCLUSIONS: RFA and EVLT offer comparable venous occlusion rates at 3 months after treatment of primary GSV varices; with neither modality proving superior. RFA is associated with less periprocedural pain, analgesic requirement, and bruising. REGISTRATION NUMBER: ISRCTN63135694 (http://www.controlled-trials.com).

Comparative proteomics reveals a systemic vulnerability in the vasculature of patients with abdominal aortic aneurysms.

INTRODUCTION: Abdominal aortic aneurysms (AAA) are associated with inflammation, apoptosis, and matrix degradation. AAA tissue represents the end stage of disease, limiting its utility in identification of factors culpable for initiation of aneurysm development. Recent evidence suggests that AAAs are a local representation of a systemic disease of the vasculature. Morphologic and molecular changes, comparable to those found in the aneurysm wall, have been demonstrated in veins from patients with AAAs. Changes in the vascular tissue proteome of patients with AAAs were investigated, using inferior mesenteric vein (IMV), to gain insight into early molecular changes contributing to AAA development. METHODS: IMV was harvested from 16 patients with AAA and 16 matched controls. Whole IMV lysates were subjected to 2-D difference in gel electrophoresis (2D-DIGE) with quantitative densitometry. Protein spots differentially expressed in AAA were identified using mass spectrometry. Differential protein expression was validated by Western blotting and localized to cell type by immunohistochemistry (IHC). RESULTS: Decreased levels of prohibitin (AAA, 2.00 ± 1.37; controls, 3.81 ± 1.39; 1.9-fold change; P = .02) AAA (7.33 ± 3.9; controls, 14.5 ± 5.6; 2-fold change; P = .001), along with relative increases in a cleaved fragment of vimentin (AAA, 12.9 ± 9; controls, 6.9 ± 4.7; 2-fold change; P = .11) were identified in AAA patients. All proteins were localized to the vascular smooth muscle cells. CONCLUSIONS: Proteins important in combating the injurious effects of oxidative stress and modulating the response to inflammation appear reduced in the vasculature of patients with AAA. These changes may represent early events in AAA formation. Enhancing expression of these proteins might offer a novel therapeutic avenue to inhibit AAA development.

Examining the impact of psychological distress on short-term postoperative outcomes after elective endovascular aneurysm repair (EVAR).

PURPOSE: Preoperative psychological factors have an impact on postoperative outcomes and there is a paucity of research in vascular surgery. The objective of this study was to examine the impact of preoperative psychological factors on short-term postoperative outcomes in an infrarenal endovascular aneurysm repair (EVAR) cohort. METHODS: A prospective, multi-centre observational study was conducted across three vascular units in England. English-speaking participants who were older than 18 years, able to provide informed consent and awaiting an elective standard infrarenal EVAR were eligible for the study. A total of 46 patients undergoing elective infrarenal AAA repair were assessed preoperatively with the State Trait Anxiety Inventory (STAI), Beck's Depression Inventory (BDI-II) and Life Orientation Test-Revised (LOT-R). Data on five short-term postoperative outcomes was collected and analysed using Spearman's rank correlations. RESULTS: Higher preoperative anxiety levels (ρ = 0.38, p = 0.01), and depression scores (ρ = 0.36, p = 0.02) were moderately correlated with an increased length of postoperative critical care stay. Higher levels of preoperative depression were moderately correlated with greater postoperative opioid analgesia use (ρ = 0.34, p = 0.02). No correlation was witnessed between optimism scores and postoperative outcomes. No correlation was witnessed with respect to total length of stay, number of complications, or time to mobilisation. CONCLUSIONS: There is a potential link between preoperative psychological well-being and short-term postoperative outcomes in an EVAR cohort. Further work is necessary to validate this link and examine the role of preoperative interventions in optimising the psychological well-being of patients undergoing EVAR.

A risk-adjusted and anatomically stratified cohort comparison study of open surgery, endovascular techniques and medical management for juxtarenal aortic aneurysms-the UK COMPlex AneurySm Study (UK-COMPASS): a study protocol.

INTRODUCTION: In one-third of all abdominal aortic aneurysms (AAAs), the aneurysm neck is short (juxtarenal) or shows other adverse anatomical features rendering operations more complex, hazardous and expensive. Surgical options include open surgical repair and endovascular aneurysm repair (EVAR) techniques including fenestrated EVAR, EVAR with adjuncts (chimneys/endoanchors) and off-label standard EVAR. The aim of the UK COMPlex AneurySm Study (UK-COMPASS) is to answer the research question identified by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme: 'What is the clinical and cost-effectiveness of strategies for the management of juxtarenal AAA, including fenestrated endovascular repair?' METHODS AND ANALYSIS: UK-COMPASS is a cohort study comparing clinical and cost-effectiveness of different strategies used to manage complex AAAs with stratification of physiological fitness and anatomical complexity, with statistical correction for baseline risk and indication biases. There are two data streams. First, a stream of routinely collected data from Hospital Episode Statistics and National Vascular Registry (NVR). Preoperative CT scans of all patients who underwent elective AAA repair in England between 1 November 2017 and 31 October 2019 are subjected to Corelab analysis to accurately identify and include every complex aneurysm treated. Second, a site-reported data stream regarding quality of life and treatment costs from prospectively recruited patients across England. Site recruitment also includes patients with complex aneurysms larger than 55 mm diameter in whom an operation is deferred (medical management). The primary outcome measure is perioperative all-cause mortality. Follow-up will be to a median of 5 years. ETHICS AND DISSEMINATION: The study has received full regulatory approvals from a Research Ethics Committee, the Confidentiality Advisory Group and the Health Research Authority. Data sharing agreements are in place with National Health Service Digital and the NVR. Dissemination will be via NIHR HTA reporting, peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: ISRCTN85731188.

Existing risk prediction methods for elective abdominal aortic aneurysm repair do not predict short-term outcome following endovascular repair.

OBJECTIVE: Improving the safety of elective abdominal aortic aneurysm (AAA) repair has become an imperative. Five well-described risk-scoring systems developed on open aneurysm repair (OR) were tested on a multicenter contemporary sample of patients undergoing endovascular repair of AAA (EVR) to determine if they predicted 30-day morbidity and mortality. METHODS: The Glasgow score (GAS), combined prognostic index (CPI), and its modification (M-CPI), the Leiden score and the Vascular Biochemical and Haematological Outctome Model (VBHOM) score were studied using a retrospective database of 846 patients. Thirty-day mortality and serious morbidity were used as end-points. A receiver-operator characteristic curves was plotted and the area under this (known as the c-statistic) was calculated to determine discriminatory ability of each model. RESULTS: Incidence of postoperative mortality was 2.2% and serious morbidity was 12.3%. All scores were predictive of mortality except the Leiden score, which had a c-statistic of 0.603 (95% CI, 0.485-0.720; P = .123). The VBHOM score and the M-CPI had a c-statistic of 0.649 (95% CI, 0.514 -0.783; P = .026) and 0.653 (95% CI, 0.544-0.763; P = .026), respectively. The best performing scores were the GAS and CPI, which had a c-statistic of 0.677 (95% CI, 0.559-0.795; P = .008) and 0.679 (95% CI, 0.572-0.787; P = .007), respectively. No score effectively predicted morbidity. CONCLUSION: None of the available scores predicted the outcome of EVR with enough accuracy to be recommended for clinical use. To improve preoperative risk prediction in EVR validation of new systems is required, taking into account morphologic features of the aneurysm to predict medium-term morbidity and re-intervention.

Toward an "off-the-shelf" fenestrated endograft for management of short-necked abdominal aortic aneurysms: an analysis of current graft morphological diversity.

PURPOSE: To examine the feasibility of an "off-the-shelf" fenestrated endograft repository to broaden the applicability of fenestrated endovascular aneurysm repair (f-EVAR) to a greater number of emergent cases. METHODS: Graft dimensions of 438 consecutive customized fenestrated endografts for juxtarenal aneurysms were obtained from the commercial manufacturer, classified into tolerance ranges, and encoded in a database for statistical analysis. Limits of variability for tolerance ranges were set to maintain target vessel patency within acceptable surgical limits at deployment. Key independent structural variables were identified and analyzed for trends. Detailed analysis was performed of 282 (64%) 3-fenestration endografts, representing 232 structurally unique grafts. RESULTS: Seven key individual structural variables were identified, constituting 21,952 possible combinations. Only 8/232 (3.5%) graft configurations were compatible with > or =3 patients. Nearly a third of the patients (86/282, 30.5%) were treated by a range of 36 customized endografts. Graft dimensions were not uniformly distributed; there were modal sizes that were likely to recur at a median 39 cases (95% CI 17-121). Deploying endografts incorporating double diameter-reducing tie technology increased the tolerance such that 28 grafts would treat 81% of this population. CONCLUSION: The current design of fenestrated stent-grafts means that an "off-the-shelf" option is not practicable. However, there is evidence of recurrent patterns of morphology. Statistical modeling is capable of predicting demand for graft configurations. Innovations in f-EVAR endograft technology may decrease the required variability in graft morphology, paving the way for ready-to-deploy fenestrated stent-grafts.

Validation of DynaCT in the morphological assessment of abdominal aortic aneurysm for endovascular repair.

PURPOSE: To evaluate the feasibility of intraoperative 3-dimensional rotational angiography (DynaCT) as a single tool to assess suitability for endovascular aneurysm repair (EVAR) and for sizing the stent-graft. METHODS: Twenty elective patients undergoing EVAR were prospectively recruited. All had preoperative multidetector computed tomography (CT) scans and intraoperative (pre-stent deployment) DynaCT scans. Images were read independently by 4 experienced endovascular practitioners. A total of 17 morphological variables, including aneurysm neck diameter and length, were measured from the CT and DynaCT images and compared. Bland-Altman plots examined intraclass correlation of continuous outcomes; kappa correlation coefficient assessed agreement of ordinal results. RESULTS: The mean DynaCT radiation dose was 3751+/-835 microGym(2). The mean difference between DynaCT and multidetector CT in aneurysm neck diameter measurement was -1.5 mm (95% CI -4.9 to 1.9). Differences in left and right common iliac artery diameters were -1.9 mm (95% CI -6.3 to 2.4) and -2.1 mm (95% CI -6.9 to 2.7), respectively. For presence of neck thrombus, the group kappa statistic was 0.51 (p<0.0001); for neck calcification, the kappa was 0.07 (p = 0.29). Nine (45%) cases had incomplete information on DynaCT because external iliac arteries were not included in the scan. CONCLUSION: DynaCT provides adequate preoperative imaging for morphological assessment of aortic anatomy. The greatest limitation is the evaluation of access vessels and underestimation of calcification. Due to current limited detector size, precise positioning is essential to attain all necessary sizing information using DynaCT.

The role of proteomic research in vascular disease.

INTRODUCTION: Arterial diseases including atherosclerosis, intimal hyperplasia and aneurysms have been shown to be a product of genotype and environment. Gene expression pathways rely on protein translation to generate target effects. As a result of alternative splicing and post-translational modifications, one gene does not code for a single protein but for many. Proteomic studies allow quantification of these proteins in a biological system and determination of altered protein expression in disease. Proteomics is a powerful and expanding field of investigation which in combination with other 'omics may enhance understanding of disease pathophysiology and/or identify biomarkers of vascular disease. This review describes the methodology of protein mining and provides an insight into the valuable contributions already made by proteomics to vascular surgery. METHODS: MEDLINE and EMBASE databases were searched for relevant articles. RESULTS: 118 relevant articles were identified. These were subdivided into categories based on the aspect of protein research they reported. The subheadings include methodology, atherosclerosis, intimal hyperplasia, aortic disease and biomarkers. CONCLUSIONS: Disease processes classified as genetic are functionally proteomic. Equally disease pathophysiology is the result of, or leads to alternate protein expression. Understanding the proteome will clarify the pathophysiology of disease. The translation of these findings to clinical practice impacts diagnosis, staging and treatment of disease processes. Biomarker discovery will enable earlier diagnosis of unstable atherosclerotic plaques, it will allow identification of aneurysms more likely to rupture and stratify risk. Proteomic research has enormous potential to modulate many aspects of patient care.

Evidence from cross-sectional imaging indicates abdominal but not thoracic aortic aneurysms are local manifestations of a systemic dilating diathesis.

INTRODUCTION: The pathogenesis of aortic aneurysms remains unclear. There is epidemiologic and histologic evidence showing significant differences in aneurysms of the thoracic and abdominal aorta. Studies suggest that abdominal aortic aneurysms (AAA) may represent a local manifestation of a systemic dilating diathesis. It is not known whether thoracic aortic aneurysms (TAA) also have a systemic etiology. The evidence for a systemic dilating diathesis in AAA disease is reviewed and supplemented with an original morphologic study based on computed tomography (CT) comparing nonaneurysmal controls with patients with AAAs and TAAs. METHODS: CT scans performed between January and November 2008 of 150 consecutive patients were examined. The morphology and dimensions of branches of the aorta in 50 TAA patients and 50 AAA patients were compared with 50 nonaneurysmal controls. Measurements of the aorta, common carotid artery (CCA), and superior mesenteric artery (SMA) were taken along with corresponding patient risk factors. RESULTS: Patients were well matched for age, gender, and comorbidity. Mean (SD) right CCA diameter was 9.3 +/- 1.2 in AAA patients vs 8.1 +/- 1 mm in TAA patients (P < .0001) and 7.9 +/- 0.9 mm in controls. Mean left CCA diameter was 9.3 +/- 1.2 mm in AAA patients vs 8.1+/- 0.8 mm in TAA patients (P < .0001) and 7.9 +/- 0.8 mm in controls. There was no significant difference in SMA morphology among the three groups: AAA, 8.6 +/- 1.1; TAA, 8.3 +/- .9; and controls, 8.4 +/- 0.9 mm. Multifactorial modeling accounting for risk factors, age, and gender confirmed that the diameter difference between groups retained independent statistical significance. CONCLUSIONS: This study provides further convincing evidence for a systemic dilating diathesis of elastic arteries in AAAs. It also highlights the differing natures of thoracic and abdominal aortic aneurysmal disease. CLINICAL RELEVANCE: A clear understanding of the pathophysiology of aortic aneurysms is essential. Observational studies have raised the suspicion that abdominal aortic aneurysms are a local representation of a systemic disease of the vasculature. Whether aneurysms of the thoracic aorta have a similar systemic tendency is unknown. Validation of this will open broader avenues of research clarifying understanding of the initiating factors of aneurysms and whether all aneurysms distributed through the arterial tree share the same etiology. This may in turn identify systemic treatments that eventually may allow targeted pharmaceutical management of small aortic aneurysms.

Endovascular management of chronic aortic dissection in patients with Marfan syndrome.

INTRODUCTION: Marfan syndrome patients are prone to aortic dilatation, dissection, and rupture. Success of aortic root replacement has generated a cohort of patients surviving longer and presenting with distal aortic dissection and enlargement. Thoracic endovascular stent-graft repair (TEVR) is being increasingly utilized to exclude aneurysms resulting from chronic aortic dissection. This report explores the role of TEVR in Marfan patients with this pathology. METHODS: Review of a prospectively maintained database identified seven patients with Marfan syndrome offered endovascular repair of aneurysmal chronic aortic dissection. All patients had previous aortic root repair. Talent or Valiant (Medtronic Vascular, Santa Rosa, Calif) aortic stent-grafts were used to occlude the dissection entry tear and cover the thoracic aorta. Electronic data, case notes, and radiological surveillance were analyzed. RESULTS: Seven consecutive patients (six male; mean age, 45.9 +/- 10 years, range, 29 to 63) underwent successful thoracic stent-graft deployment. Mean aortic aneurysmal diameter was 63.4mm (+/-11.2) with six of seven dissections extending to the aortic bifurcation. No perioperative neurological events occurred. Thirty-day mortality was 1/7 (14%) due to congestive cardiac failure. At median 16 month follow-up, two of six cases (33%) required intervention for endoleak. Aortic false lumen thrombosis (FLT) occurred in 5/6 (83%) cases and partial FLT occurred in 1/6 (17%). All thoracic aortas continued to dilate during follow-up. Crude median aortic growth rate was 7.2 mm/year (range, 3.5 to 19 mm). CONCLUSION: TEVR in Marfan syndrome patients with chronic aortic dissection is technically feasible. However, post intervention surveillance confirms that the aorta continues to dilate despite graft deployment and false lumen thrombosis. Endovascular repair may offer a viable option in patients who have contraindications to open surgery, but longer follow up of more patients is required to define the place of this therapy.

Patient Compliance with Surveillance Following Elective Endovascular Aneurysm Repair.

PURPOSE: Integral to maintaining good outcomes post-endovascular aneurysm repair (EVAR) is a robust surveillance protocol. A significant proportion of patients fail to comply with surveillance, exposing themselves to complications. We examine EVAR surveillance in Wessex (UK), exploring factors that may predict poor compliance. METHODS: Retrospective analysis of 179 consecutive elective EVAR cases [2008-2013] was performed. 167 patients were male, with the age range of 50-95. Surveillance was conducted centrally (tertiary referral trauma centre) and at four spoke units. Surveillance compliance and predictors of non-compliance including age, gender, co-morbid status, residential location and socioeconomic status were analysed for univariate significance. RESULTS: Fifty patients (27.9 %) were non-compliant with surveillance; 14 (8.1 %) had no imaging post-EVAR. At 1 year, 56.1 % (of 123 patients) were compliant. At years 2 and 3, 41.5 and 41.2 % (of 65 and 34 patients, respectively) were compliant. Four years post-EVAR, only one of eight attended surveillance (12.5 %). There were no statistically significant differences in age (p = 0.77), co-morbid status or gender (p = 0.64). Distance to central unit (p = 0.67) and surveillance site (p = 0.56) was non-significant. While there was a trend towards compliance in upper-middle-class socioeconomic groups (ABC1 vs. C1C2D), correlating with >50 % of non-compliant patients living within <10 mile radius of the central unit, overall predictive value was not significant (p = 0.82). CONCLUSIONS: Compliance with surveillance post-EVAR is poor. No independent predictor of non-compliance has been confirmed, but socioeconomic status appears to be relevant. There is a worrying drop-off in attendance beyond the first year. This study highlights a problem that needs to be addressed urgently, if we are to maintain good outcomes post-EVAR.

Increased Expression of Lamin A/C Correlate with Regions of High Wall Stress in Abdominal Aortic Aneurysms.

BACKGROUND: Since aortic diameter is the most -significant risk factor for rupture, we sought to identify stress-dependent changes in gene expression to illuminate novel molecular processes in aneurysm rupture. MATERIALS AND METHODS: We constructed finite element maps of abdominal computerized tomography scans (CTs) of seven abdominal aortic aneurysm (AAA) patients to map wall stress. Paired biopsies from high- and low-stress areas were collected at surgery using vascular landmarks as coordinates. Differential gene expression was evaluated by Illumina Array analysis, using the whole genome DNA-mediated, annealing, selection, extension, and ligation (DASL) gene chip (n = 3 paired samples). RESULTS: The sole significant candidate from this analysis, Lamin A/C, was validated at the protein level, using western blotting. Lamin A/C expression in the inferior mesenteric vein (IMV) of AAA patients was compared to a control group and in aortic smooth muscle cells in culture in response to physiological pulsatile stretch. -Areas of high wall stress (n = 7) correlate to those -regions which have the thinnest walls [778 µm (585-1120 µm)] in comparison to areas of lowest wall stress [1620 µm (962-2919 µm)]. Induced expression of Lamin A/C -correlated with areas of high wall stress from AAAs but was not significantly induced in the IMV from AAA patients compared to controls (n = 16). Stress-induced expression of Lamin A/C was mimicked by exposing aortic smooth muscle cells to prolonged pulsatile stretch. CONCLUSION: Lamin A/C protein is specifically increased in areas of high wall stress in AAA from patients, but is not increased on other vascular beds of aneurysm patients, suggesting that its elevation may be a compensatory response to the pathobiology leading to aneurysms.

Pathophysiology and epidemiology of abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAAs) are found in up to 8% of men aged >65 years, yet usually remain asymptomatic until they rupture. Rupture of an AAA and its associated catastrophic physiological insult carries overall mortality in excess of 80%, and 2% of all deaths are AAA-related. Pathologically, AAAs are associated with inflammation, smooth muscle cell apoptosis, and matrix degradation. Once thought to be a consequence of advanced atherosclerosis, accruing evidence indicates that AAAs are a focal representation of a systemic disease of the vasculature. Risk factors for AAAs include increasing age, male sex, smoking, and low HDL-cholesterol levels. Familial associations exist and although susceptibility genes have been described on the basis of candidate-gene studies, robust genetic studies have failed to discover causative gene mutations. The surgical management of AAAs has been revolutionized by minimally invasive endovascular repair. Ongoing randomized trials will establish whether endovascular repair confers a survival advantage over open surgery for patients with a ruptured AAA. In many countries, centralization of vascular surgical services has largely been driven by the improved outcomes of elective aneurysm surgery in specialized centers, the widespread adoption of endovascular techniques, and the introduction of screening programs.

Management of acute aortic syndrome and chronic aortic dissection.

Acute aortic syndrome (AAS) describes several life-threatening aortic pathologies. These include intramural hematoma, penetrating aortic ulcer, and acute aortic dissection (AAD). Advances in both imaging and endovascular treatment have led to an increase in diagnosis and improved management of these often catastrophic pathologies. Patients, who were previously consigned to medical management or high-risk open surgical repair, can now be offered minimally invasive solutions with reduced morbidity and mortality. Information from the International Registry of Acute Aortic Dissection (IRAD) database demonstrates how in selected patients with complicated AAD the 30-day mortality from open surgery is 17% and endovascular stenting is 6%. Despite these improvements in perioperative deaths, the risks of stroke and paraplegia remain with endovascular treatment (combined outcome risk 4%). The pathophysiology of each aspect of AAS is described. The best imaging techniques and the evolving role of endovascular techniques in the definitive management of AAS are discussed incorporating strategies to reduce perioperative morbidity.

Proteomics and pitfalls in the search for potential biomarkers of abdominal aortic aneurysms.

Proteomics is evolving as an important research technique in cardiovascular disease. We present exploratory research for a systemic biomarker of abdominal aortic aneurysm (AAA) in serum. Forty patients, 20 with large AAAs and 20 matched controls, were prospectively recruited. Serum was harvested, enriched, and mined for differential protein expression. Difference in gel electrophoresis using a two-dimensional platform, cyanine labeling, and Progenesis SameSpots software identified protein spots with significantly altered intensity. Liquid chromatography mass spectrometry aligned to the Seaquest protein database characterized proteins of interest, and 436 protein spots were demonstrated from the 20 processed gels. Thirteen spots of interest, demonstrating fold change (1.7-4) between the two patient cohorts and consistent significant differential expression (analysis of variance, p