The utilisation of vascular limb salvage services in the assessment and management of chronic limb-threatening ischaemia and diabetic foot ulceration: A systematic review.

Specialist vascular limb salvage services have gained prominence as a new model of care to help overcome barriers which exist in the management of patients with chronic limb-threatening ischaemia (CLTI) and/or diabetic foot ulceration (DFU). This systematic review aims to explore the nature of reported services, investigate their outcome in the management of CLTI/DFU, and assess the scope and quality of the evidence base to help make recommendations for future practice and research. A systematic search of MEDLINE, Embase, The Cochrane Library, Scopus and CINAHL, from 1st January 1995 to 18th January 2019, was performed. Specialist vascular limb salvage services were defined as those services conforming to the definition of "centres of excellence" within the 2019 Global Vascular Guidelines. A study protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42019123325). In total, 2260 articles were screened, with 12 articles (describing 11 services) included in a narrative synthesis. All services ran akin to the "toe-and-flow" model, with a number of services having additional core input from diabetology, microbiology, allied health professionals and/or internal/vascular medicine. Methodological weaknesses were identified within the design of the included articles and only one was deemed of high quality. The inception of services was associated with improved rates of major amputation; however, no significant changes in minor amputation or mortality rates were identified. Further research should adopt more a standardised study design and outcomes measures in order to improve the quality of evidence within the literature.

Post-Carotid Endarterectomy Hypertension. Part 1: Association with Pre-operative Clinical, Imaging, and Physiological Parameters.

OBJECTIVE/BACKGROUND: Post-endarterectomy hypertension (PEH) is a well recognised, but poorly understood, phenomenon after carotid endarterectomy (CEA) that is associated with post-operative intracranial haemorrhage, hyperperfusion syndrome, and cardiac complications. The aim of the current study was to identify pre-operative clinical, imaging, and physiological parameters associated with PEH. METHODS: In total, 106 CEA patients undergoing CEA under general anaesthesia underwent pre-operative evaluation of 24 hour ambulatory arterial blood pressure (BP), baroreceptor sensitivity, cerebral autoregulation, and transcranial Doppler measurement of cerebral blood flow velocity (CBFv) and pulsatility index. Patients who met pre-existing criteria for treating PEH after CEA (systolic BP [SBP] > 170 mmHg without symptoms or SBP > 160 mmHg with headache/seizure/neurological deficit) were treated according to a previously established protocol. RESULTS: In total, 40/106 patients (38%) required treatment for PEH at some stage following CEA (26 in theatre recovery [25%], 27 while on the vascular surgical ward [25%]), while seven (7%) had SBP surges > 200 mmHg back on the ward. Patients requiring treatment for PEH had a significantly higher pre-operative SBP (144 ± 11 mmHg vs. 135 ± 13 mmHg; p < .001) and evidence of pre-existing impairment of baroreceptor sensitivity (3.4 ± 1.7 ms/mmHg vs. 5.3 ± 2.8 ms/mmHg; p = .02). However, PEH was not associated with any other pre-operative clinical features, CBFv, or impaired cerebral haemodynamics. Paradoxically, autoregulation was better preserved in patients with PEH. All four cases of hyperperfusion associated symptoms were preceded by PEH. Length of hospital stay was significantly increased in patients with PEH (p < .001). CONCLUSION: In this study, where all patients underwent CEA under general anaesthesia, PEH was associated with poorly controlled pre-operative BP and impaired baroreceptor sensitivity, but not with other peripheral or central haemodynamic parameters, including impaired cerebral autoregulation.

Meta-analysis of Outcomes Following Aneurysm Repair in Patients with Synchronous Intra-abdominal Malignancy.

OBJECTIVES: The management of concomitant intra-abdominal malignancy (IAM) and abdominal aortic aneurysm (AAA) remains a challenge, even though malignancy is common in an elderly population. By means of systematic review and meta-analysis, the aim was to investigate outcomes in patients undergoing open (OAR) or endovascular AAA repair (EVAR) that have a concomitant malignancy. METHODS: A systematic literature review was performed (Medline and EMBASE databases) to identify all series reporting outcomes of AAA repair (OAR or EVAR) in patients with concomitant IAM. Meta-analysis was applied to assess mortality and major morbidity at 30 days and long term. RESULTS: The literature review identified 36 series (543 patients) and the majority (18 series) reported on patients with colorectal malignancy and AAA. Mean weighted mortality for OAR at 30 days was 11% (95% CI: 6.6% to 17.9%); none of the EVAR patients died peri-operatively. The weighted 30-day major complication rate for EVAR was 20.4% (10.0-37.4%) and for OAR it was 15.4% (7.0-30.8%). Most patients had their AAA and malignancy treated non-simultaneously (56.6%, 95% CI, 42.1-70.1%). In the EVAR cohort, three patients (4.6%) died at last follow-up (range 24-64 months). In the OAR cohort 23 (10.6%) had died at last follow up (range from 4 to 73 months). CONCLUSION: In this meta-analysis, OAR was associated with significant peri-operative mortality in patients with an IAM. EVAR should be the first-line modality of AAA repair. The majority of patients were not treated simultaneously for the two pathologies, but further investigation is necessary to define the optimal timing for each procedure and malignancy.

Microarray-based Gene Expression Profiling of Abdominal Aortic Aneurysm.

OBJECTIVE/BACKGROUND: Microarray-based gene expression profiling studies may detect transcriptional signatures carrying prognostic value in abdominal aortic aneurysms (AAA). A gene expression profiling study was conducted to compare individuals with AAA with screened controls. METHODS: The peripheral blood transcriptome was compared between 12 individuals with AAA and 12 age- and sex-matched controls using microarray. Validation by Taqman real-time quantitative (qPCR) was performed in an independent group as described. Peripheral blood RNA was hybridized to Illumina microarrays, each representing 37,846 genes, allowing comparison of gene expression between cases and controls. Eleven differentially expressed genes were re-quantified by qPCR in the independent group with AAA (n = 95), controls (n = 92), pre- and postendovascular AAA repair (EVAR, n = 31); or open AAA repair (n = 13), AAA wall biopsies (n = 11), and in matched smooth muscle cultures (n = 7). RESULTS: Microarray detected 47 significantly differentially expressed genes in AAA after correction for multiple testing (p < .05). These genes conferred roles in regulation of apoptosis, proteolysis, the electron transport chain, leukocyte migration, and the humoral immune response. Gene quantification in the independent group demonstrated three genes to be downregulated in AAA compared with controls: MSN, PSMB10, and STIM1; however, their expression remained unchanged post-AAA repair. PSMB10 was the only gene conferring a consistent direction of effect in both the discovery and validation analyses (downregulated). EIF3G, SIVA, PUF60, CYC1, FIBP, and CARD8 were downregulated post-EVAR. Expression of all 11 genes of interest was detected in aortic biopsies and matched smooth muscle cultures. CONCLUSION: This study demonstrates differential expression of transcripts in peripheral blood of individuals with AAA, with functional roles in proteolysis, inflammation, and apoptotic processes. These were modulated by aneurysm exclusion from the circulation and expressed in matched aortic biopsies and smooth muscle cultures. These observations further support the key roles for these pathways in the pathogenesis of AAA.

Gene and Protein Expression of Chemokine (C-C-Motif) Ligand 19 is Upregulated in Unstable Carotid Atherosclerotic Plaques.

OBJECTIVE/BACKGROUND: The aim was to investigate the expression of genes associated with carotid plaque instability and their protein products at a local and systemic level. METHODS: Carotid plaques from 24 patients undergoing carotid endarterectomy (CEA) were classified as stable or unstable using clinical, histological, ultrasound, and transcranial Doppler criteria, and compared using whole genome microarray chips. Initial results of differentially expressed genes were validated by quantitative reverse transcriptase polymerase chain reaction in an independent group of 96 patients undergoing CEA. The protein product of genes significantly differentially expressed between patients with stable and unstable plaques were analysed by plaque immunohistochemistry and serum protein quantification by enzyme-linked immunosorbent assay on a further independent cohort. RESULTS: Expression of chemokine (c-c-motif) ligand 19 (CCL19) was significantly upregulated in plaques from patients with clinically unstable disease (p < .001). Cathepsin G expression was upregulated in histologically unstable plaques (p = .04). Serum concentration of CCL19 was significantly higher in patients with clinically unstable plaques (p = .02). Immunohistochemical staining for CCL19 demonstrated positive staining in histologically and clinically unstable plaques (p = .03). CCL19 also co-localised with CD3+ T-cell lymphocytes in the core region, around where CCL19 was expressed. CONCLUSIONS: CCL19 is significantly overexpressed in patients with unstable carotid atherosclerotic plaques and may be a possible novel biomarker for identifying high-risk patients in whom more urgent intervention may be indicated.

Survey of ankle-brachial pressure index use and its perceived barriers by general practitioners in the UK.

BACKGROUND: Peripheral arterial disease (PAD) is often undetected until complications arise, despite it being a major healthcare burden and an independent risk factor for cardiovascular death and systemic atherosclerosis. Appropriate diagnostic tools are as important as clinical knowledge and skill to investigate patients for PAD. Currently, the ankle-brachial pressure index (ABPI) is the recommended diagnostic tool for PAD. PURPOSE: We explore current opinions on ABPI by general practitioners (GPs) and the limitations to its implementation in primary care practice. METHODS: GPs attending a regional 1-day study event, were surveyed in October 2014. Survey questionnaires were placed at the top of each conference pack for each attendee. The survey questionnaire was modelled from the ankle-brachial index (ABI) usage survey questionnaire used in the PAD Awareness, Risk and Treatment: New Resources for Survival (PARTNERS) preceptorship study. RESULTS: All respondents were GPs, with a survey response rate of 77.1%. All respondents regarded ABPI as an important test, that is primarily performed by nursing staff (79.5%) in their respective GP surgeries. 70% and 97% of GPs found ABPI useful for the diagnosis of asymptomatic and symptomatic PAD, respectively. 69% of GPs regarded ABPI as a feasible test in primary care practice. Time constraints (84%), staff availability (89%) and staff training (72%) were cited as the main limitations to its use. CONCLUSIONS: Targeted training of nursing staff may improve ABPI usage, although a less time-consuming test for PAD may be another option.

Systematic review of cardiovascular disease and cardiovascular death in patients with a small abdominal aortic aneurysm.

BACKGROUND: Screening for abdominal aortic aneurysm (AAA) has reduced the rate of AAA rupture. However, cardiovascular disease is still a major cause of death in men with an AAA. The aim of this study was to assess cardiovascular risk in patients with a small AAA. METHODS: Standard PRISMA guidelines were followed. Analysis was performed of studies reporting cardiovascular outcomes in patients with a small AAA (30-54 mm). Weighted metaregression was performed for cardiovascular death in patients with a small AAA, and the prevalence of cardiovascular disease was reviewed. RESULTS: Twenty-one articles were identified describing patients with an AAA, and the prevalence of, and death from, cardiovascular disease. Ten of these reported cardiovascular death rates in patients with a small AAA. Some 2323 patients with a small AAA were identified; 335 cardiovascular deaths occurred, of which 37 were due to AAA rupture. Metaregression demonstrated that the risk of cardiovascular death was 3·0 (95 per cent c.i. 1·7 to 4·3) per cent per year in patients with a small AAA (R(2) = 0·902, P < 0·001). The prevalence of ischaemic heart disease (44·9 per cent), myocardial infarction (26·8 per cent), heart failure (4·4 per cent) and stroke (14·0 per cent) was also high in these patients. CONCLUSION: The risk of cardiovascular death in patients with a small AAA is high and increases by approximately 3 per cent each year after diagnosis. Patients with a small AAA have a high prevalence of cardiovascular disease. Patients a small AAA should be considered for lifestyle modifications and secondary cardiovascular protection.

Identification of microRNAs associated with abdominal aortic aneurysms and peripheral arterial disease.

BACKGROUND: MicroRNAs are crucial in the regulation of cardiovascular disease and represent potential therapeutic targets to decrease abdominal aortic aneurysm (AAA) expansion. The aim of this study was to identify circulating microRNAs associated with AAA. METHODS: Some 754 microRNAs in whole-blood samples from 15 men with an AAA and ten control subjects were quantified using quantitative reverse transcriptase-PCR. MicroRNAs demonstrating a significant association with AAA were validated in peripheral blood and plasma samples of men in the following groups (40 in each): healthy controls, controls with peripheral arterial disease (PAD), men with a small AAA (30-54 mm), those with a large AAA (over 54 mm), and those following AAA repair. MicroRNA expression was also assessed in aortic tissue. RESULTS: Twenty-nine differentially expressed microRNAs were identified in the discovery study. Validation study revealed that let-7e (fold change (FC) -1·80; P = 0·001), miR-15a (FC -2·24; P < 0·001) and miR-196b (FC -2·26; P < 0·001) were downregulated in peripheral blood from patients with an AAA, and miR-411 was upregulated (FC 5·90; P = 0·001). miR-196b was also downregulated in plasma from the same individuals (FC -3·75; P = 0·029). The same miRNAs were similarly expressed differentially in patients with PAD compared with healthy controls. Validated and predicted microRNA targets identified through miRWalk revealed that these miRNAs were all regulators of AAA-related genes (vascular cell adhesion molecule 1, intercellular cell adhesion molecule 1, DAB2 interacting protein, α1-antitrypsin, C-reactive protein, interleukin 6, osteoprotegerin, methylenetetrahydrofolate reductase, tumour necrosis factor α). CONCLUSION: In this study, circulating levels of let-7e, miR-15a, miR-196b and miR-411 were differentially expressed in men with an AAA compared with healthy controls, but also differentially expressed in men with PAD. Modulation of these miRNAs and their target genes may represent a new therapeutic pathway to affect the progression of AAA and atherosclerosis.

National Vascular Registry Report on surgical outcomes and implications for vascular centres.

BACKGROUND: The National Vascular Registry Report on Surgical Outcomes (NVSRO) coincided with the update of the National Health Service Standard Contract for Specialized Vascular Services in Adults (NHSSCSVS). The latter promises patients minimum standards for vascular centres. The present study aimed to determine whether current data support the standards proposed in the NHSSCSVS. METHODS: Numbers of abdominal aortic aneurysm (AAA) repairs and carotid endarterectomies (CEAs) performed by hospital Trust and surgeon, and their outcomes were obtained from the NVRSO. These were assessed against NHSSCSVS recommendations that included: more than 60 AAA repairs per year per Trust, over 50 CEAs per year per Trust and at least six vascular surgeons per Trust. RESULTS: Based on NVRSO data, 107 hospital Trusts (92.2 per cent) would fail to meet the minimum standards required to achieve vascular centre status. Outcomes were poorer in these hospitals (overall mortality rate after AAA: 2.7 versus 1.3 per cent; P = 0.007). There were strong associations between number of AAA repairs or CEAs per Trust and better outcomes (AAA repair, P < 0.001; CEA, P = 0.004). These remained significant when analysed by individual surgeon (AAA repair, P < 0.001; CEA, P < 0.001). Trusts undertaking 60 or fewer elective AAA repairs per year had significantly higher elective AAA mortality rates (2.7 versus 1·7 per cent; P = 0.010). Trusts performing a minimum of 50 CEAs per year had significantly lower perioperative mortality/morbidity rates (1.9 versus 3.0 per cent; P = 0.032). Trusts with seven or more surgeons demonstrated lower AAA-related mortality rates (1.7 versus 2.7 per cent; P = 0.018). CONCLUSION: Data from the NVRSO suggest that the majority of hospital Trusts presently fail to meet the standards for vascular centre status. NVRSO data support a standard of more than 60 elective AAA repairs and 50 CEAs per Trust per year. A minimum of seven vascular surgeons per unit was associated with better outcomes. These data support the ongoing remodelling of vascular services in the UK.

Meta-analysis and meta-regression analysis of biomarkers for abdominal aortic aneurysm.

BACKGROUND: Many studies have investigated the systemic and local expression of biomarkers in patients with abdominal aortic aneurysm (AAA). The natural history of AAA varies between patients, and predictors of the presence and diameter of AAA have not been determined consistently. The aim of this study was to perform a systematic review, meta-analysis and meta-regression of studies comparing biomarkers in patients with and without AAA, with the aim of summarizing the association of identified markers with both AAA presence and size. METHODS AND RESULTS: Literature review identified 106 studies suitable for inclusion. Meta-analysis demonstrated a significant difference between matrix metalloproteinase (MMP) 9, tissue inhibitor of matrix metalloproteinase 1, interleukin (IL) 6, C-reactive protein (CRP), α1-antitrypsin, triglycerides, lipoprotein(a), apolipoprotein A and high-density lipoprotein in patients with and without AAA. Although meta-analysis was not possible for MMP-2 in aortic tissue, tumour necrosis factor α, osteoprotegerin, osteopontin, interferon γ, intercellular cell adhesion molecule 1 and vascular cell adhesion molecule 1, systematic review suggested an increase in these biomarkers in patients with AAA. Meta-regression analysis identified a significant positive linear correlation between aortic diameter and CRP level. CONCLUSION: A wide variety of biomarkers are dysregulated in patients with AAA, but their clinical value is yet to be established. Future research should focus on the most relevant biomarkers of AAA, and how they could be used clinically.

What is the best option for elective repair of an abdominal aortic aneurysm in a young fit patient?

OBJECTIVE: The lower procedural risk associated with endovascular aneurysm repair (EVAR) compared with open aneurysm repair (OAR) is well known. Younger patients are likely to represent a group at low perioperative risk. The long-term durability and late complications following EVAR may have more significance when considering the optimal treatment for young patients with a longer life expectancy. This study examined perioperative and long-term outcomes of young patients undergoing aneurysm repair by either open surgical or endovascular means. METHODS: A retrospective review of a prospectively collated database was performed. Patients undergoing elective aneurysm repair at the age of 65 years or younger between January 2000 and September 2010 were included. All EVAR patients were followed up in a nurse-led clinic. Data regarding long-term outcomes for patients undergoing open repair were gathered from case note review. RESULTS: There were 99 patients who underwent open repair and 59 patients who underwent endovascular repair. Groups were well matched in terms of demographics and co-morbidities. 30-day mortality was 1% after open repair. There were no perioperative deaths after endovascular repair. Overall, 30-day complication rates were 15% after open repair and 12% after EVAR. The nature of complications differed between the two groups with the EVAR group experiencing endoleaks and the OAR group demonstrating more cardiorespiratory complications. Mean follow-up was 75.5 months and there was a 14% reintervention rate after EVAR compared with 7% after OAR. CONCLUSION: Young patients are likely to have a lower procedural risk for EVAR and OAR than described in published figures. Although mortality and complication rates in these two groups were similar, the nature of complications occurring following open surgery were often more significant than those occurring after EVAR. There remains a risk of late reintervention following either form of repair.

Type II endoleak: conservative management is a safe strategy.

OBJECTIVE: Type II endoleak is the most common complication after endovascular abdominal aortic aneurysm repair (EVAR); however, its natural history is unclear. The aim of this study was to examine the incidence and outcomes of type II endoleak, at a single institution after EVAR. METHODS: A total of 904 consecutive patients who underwent EVAR between September 1995 and July 2013 at a single centre were entered onto a prospective database. All patients were followed up by duplex ultrasound (DUSS). Patients who developed type II endoleak were compared for preoperative demographics, mortality, and sac expansion. RESULTS: A total of 175(19%) patients developed type II endoleak over a median follow-up of 3.6 years (1.5-5.9 years); 54% of type II endoleaks spontaneously resolved within 6 months (0.25-1.2 years). No difference was found in preoperative demographics or choice of endograft between the two groups. Survival was significantly higher in the group with type II endoleak (94.1% vs. 85.6%; p = .01) and this effect was most pronounced in those with late type II endoleaks (97.7% vs. 85.6% p = .004). No difference was seen in aneurysm-related mortality or rate of type I endoleak between the two groups. Freedom from sac expansion (>5 mm from preoperative diameter) was significantly lower in the group of patients with type II endoleak (82.5% vs. 93.2%, p = .0001); however, at a threshold of >10 mm from preoperative diameter no difference was seen. CONCLUSIONS: Patients with isolated type II endoleak demonstrate equivalent aneurysm-related mortality and an improved survival.

A review of current reporting of abdominal aortic aneurysm mortality and prevalence in the literature.

BACKGROUND: It is common for authors to introduce a paper by demonstrating the importance of the clinical condition being addressed, usually by quoting data such as mortality and prevalence rates. Abdominal aortic aneurysm (AAA) epidemiology is changing, and therefore such figures for AAA are subject to error. The aim of this study was to analyse the accuracy of AAA prevalence and mortality citations in the contemporaneous literature. METHODS: Two separate literature searches were performed using PubMed to identify studies reporting either aneurysm prevalence or mortality. The first 40 articles or those published over the last 2 years were included in each search to provide a snapshot of current trends. For a prevalence citation to be appropriate, a paper had to cite an original article publishing its own prevalence of AAA or a national report. In addition, the cited prevalence should match that published within the referenced article. These reported statistics were compared with the most recent data on aneurysm-related mortality. RESULTS: The prevalence of AAA was reported to be as low as 1% and as high as 12.7% (mean 5.7%, median 5%). Only 47.5% of studies had referenced original articles, national reports or NICE, and only 32.4% of cited prevalences matched those from the referenced article. In total 5/40 studies were completely accurate. 80% of studies cited aneurysm mortality in the USA, with the majority stating 15,000 deaths per year (range 9,000 to 30,000). Current USA crude AAA mortality is 6,289 (2010). CONCLUSION: References for AAA mortality and prevalence reported in the current literature are often inaccurate. This study highlights the importance of accurately reporting mortality and prevalence data and using up-to-date citations.

Identification of patients with a histologically unstable carotid plaque using ultrasonic plaque image analysis.

OBJECTIVES: In patients with carotid stenosis the risk of stroke is highest in the first few days after onset of symptoms and it is low in asymptomatic patients. The ability to identify patients with a high (or low) probability of having a histologically unstable plaque might become a complimentary method that can refine the indications for surgical intervention. METHODS: Two histopathologists, using validated American Heart Association criteria, independently graded plaques harvested during carotid endarterectomy. Preoperative Duplex images were independently assessed for juxtaluminal black area, plaque type, plaque area, and grey-scale median (GSM) following image normalization. Logistic regression analysis was then performed to create a model for predicting predominantly histologically unstable or stable plaques. RESULTS: A total of 126 patients were included in the study. Based on the presence and extent of histological features including haemorrhage, thrombus, fibrous tissue, lipid core, inflammation, neovascularity, foam cells, and cap rupture, 39 plaques were graded as predominantly stable, while 87 were predominantly unstable. Unstable plaques were associated with a plaque area >95 mm(2) (OR 4.15; 95% CI 1.34-12.8 p = .009), a juxtaluminal black area >6 mm(2) (OR 2.77; 95% CI 1.24 to 6.17 p = .01) and a GSM <25 (OR 3.76; 95% CI 1.14-12.39). Logistic regression indicated that patients with the first two features had a 90% probability of having a histologically unstable plaque. The model was used to calculate the probability of having an unstable plaque in each patient. The receiver operating characteristic curve using the p value was 0.68 (95% CI 0.59-0.78). CONCLUSIONS: Computerized plaque analysis has the potential to identify patients with histologically unstable carotid plaques. This model requires validation, but offers the potential to influence patient selection for emergency interventions and the monitoring of medical therapy.

Systematic review and meta-analysis of the early and late outcomes of open and endovascular repair of abdominal aortic aneurysm.

BACKGROUND: Any possible long-term benefit from endovascular (EVAR) versus open surgical repair for abdominal aortic aneurysm (AAA) remains unproven. Long-term data from the Open Versus Endovascular Repair (OVER) trial add to the debate regarding long-term all-cause and aneurysm-related mortality. The aim of this study was to investigate 30-day and long-term mortality, reintervention, rupture and morbidity after EVAR and open repair for AAA in a systematic review. METHODS: Standard PRISMA guidelines were followed. Random-effects Mantel-Haenszel meta-analysis was performed to evaluate mortality and morbidity outcomes. RESULTS: The existing published randomized trials, together with information from Medicare and SwedVasc databases, were included in a meta-analysis. This included 25 078 patients undergoing EVAR and 27 142 undergoing open repair for AAA. Patients who had EVAR had a significantly lower 30-day or in-hospital mortality rate (1·3 per cent versus 4·7 per cent for open repair; odds ratio (OR) 0·36, 95 per cent confidence interval 0·21 to 0·61; P < 0·001). By 2-year follow-up there was no difference in all-cause mortality (14·3 versus 15·2 per cent; OR 0·87, 0·72 to 1·06; P = 0·17), which was maintained after at least 4 years of follow-up (34·7 versus 33·8 per cent; OR 1·11, 0·91 to 1·35; P = 0·30). There was no significant difference in aneurysm-related mortality by 2 years or longer follow-up. A significantly higher proportion of patients undergoing EVAR required reintervention (P = 0·003) and suffered aneurysm rupture (P < 0·001). CONCLUSION: There is no long-term survival benefit for patients who have EVAR compared with open repair for AAA. There are also significantly higher risks of reintervention and aneurysm rupture after EVAR.

Type II endoleak after endovascular aneurysm repair.

BACKGROUND: The aim was to assess the risk of rupture, and determine the benefits of intervention for the treatment of type II endoleak after endovascular abdominal aortic aneurysm repair (EVAR). METHODS: This systematic review was done according to PRISMA guidelines. Outcome data included incidence, spontaneous resolution, sac expansion, interventions, clinical success, and complications including conversion to open repair, and rupture. RESULTS: Thirty-two non-randomized retrospective studies were included, totalling 21 744 patients who underwent EVAR. There were 1515 type II endoleaks and 393 interventions. Type II endoleak was seen in 10·2 per cent of patients after EVAR; 35·4 per cent resolved spontaneously. Fourteen patients (0·9 per cent) with isolated type II endoleak had ruptured abdominal aortic aneurysm; six of these did not have known aneurysm sac expansion. Of 393 interventions for type II endoleak, 28·5 per cent were unsuccessful. Translumbar embolization had a higher clinical success rate than transarterial embolization (81 versus 62·5 per cent respectively; P = 0·024) and fewer recurrent endoleaks were reported (19 versus 35·8 per cent; P = 0·036). Transarterial embolization also had a higher rate of complications (9·2 per cent versus none; P = 0·043). CONCLUSION: Aortic aneurysm rupture after EVAR secondary to an isolated type II endoleak is rare (less than 1 per cent), but over a third occur in the absence of sac expansion. Translumbar embolization had a higher success rate with a lower risk of complications.

Predicting aortic complications after endovascular aneurysm repair.

BACKGROUND: Lifelong surveillance is standard after endovascular repair of abdominal aortic aneurysm (EVAR), but remains costly, heterogeneous and poorly calibrated. This study aimed to develop and validate a scoring system for aortic complications after EVAR, informing rationalized surveillance. METHODS: Patients undergoing EVAR at two centres were studied from 2004 to 2010. Preoperative morphology was quantified using three-dimensional computed tomography according to a validated protocol, by investigators blinded to outcomes. Proportional hazards modelling was used to identify factors predicting aortic complications at the first centre, and thereby derive a risk score. Sidak tests between risk quartiles dichotomized patients to low- or high-risk groups. Aortic complications were reported by Kaplan-Meier analysis and risk groups were compared by log rank test. External validation was by comparison of aortic complications between risk groups at the second centre. RESULTS: Some 761 patients, with a median age of 75 (interquartile range 70-80) years, underwent EVAR. Median follow-up was 36 (range 11-94) months. Physiological variables were not associated with aortic complications. A morphological risk score incorporating maximum aneurysm diameter (P < 0·001) and largest common iliac diameter (measured 10 mm from the internal iliac origin; P = 0·004) allocated 75 per cent of patients to a low-risk group, with excellent discrimination between 5-year rates of aortic complication in low- and high-risk groups at both centres (centre 1: 12 versus 31 per cent, P < 0·001; centre 2: 12 versus 45 per cent, P = 0·002). CONCLUSION: The risk score uses commonly available morphological data to stratify the rate of complications after EVAR. The proposals for rationalized surveillance could provide clinical and economic benefits.

Changes in middle cerebral artery velocity after carotid endarterectomy do not identify patients at high-risk of suffering intracranial haemorrhage or stroke due to hyperperfusion syndrome.

OBJECTIVES: To determine if significant increases in middle cerebral artery velocity (MCAV) or pulsatility index (PI) during and immediately after carotid endarterectomy (CEA) were predictive of patients suffering a stroke due to the hyperperfusion syndrome (HS) or intracerebral haemorrhage (ICH). METHODS: Transcranial Doppler (TCD) mean/peak MCAV and PI were recorded pre-operatively; pre-clamp; 1-min post-declamping; 10-min post-declamping and 30-min post-operatively. The study was divided into two time periods; Group 1 (1995-2007); where there was no formal guidance for managing post-CEA hypertension (PEH) and Group 2 (2008-2012); where written guidelines for treating PEH were available. RESULTS: 11/1024 patients in Group 1 (1.1%) suffered a stroke due to HS/ICH, compared to 0/426 patients (0.0%) in Group 2 (p = 0.02). In Group 1; intra-operative increases >100% in mean/peak MCAV and PI at 1 and 10-min post-clamp release had positive predictive values (PPV) of 1.2%, 6.3% and 20.0% and 2.9%, 8.0% and 16.6% respectively. Post-operatively; a >100% increase in mean and peak MCAV had a PPV of 6.3% and 2.7% respectively. CONCLUSION: We were unable to demonstrate that significant increases in MCAV and PI were able to predict patients at increased risk of suffering a post-operative stroke due to HS or ICH. The provision of written guidance for managing PEH in Group 2 patients was associated with virtual abolition of ICH/HS.

Features of unstable carotid plaque during and after the hyperacute period following TIA/stroke.

BACKGROUND: The aim was to test the hypothesis that histologically unstable carotid plaque features were more prevalent in patients undergoing carotid endarterectomy (CEA) in the acute period after onset of symptoms and that the plaque would assume more stable histological characteristics as the delay from the most recent event increased. METHODS: Seven histological features of plaque instability (haemorrhage, large lipid core, chronic plaque inflammation, chronic cap inflammation, marked vascularity, cap rupture and many foam cells) were independently quantified and then correlated with recency of symptoms in patients undergoing CEA. RESULTS: In patients undergoing CEA ≤14 days of their last event, 87/119 (73%) exhibited ≥5/7 unstable histological plaque features, compared with 22/40 (55%) of patients undergoing delayed surgery (P = 0.048). As expected, there was a sustained decline in the prevalence of unstable plaque features in 61 patients undergoing surgery between days 7-28. However, there was then a marked increase in the prevalence of plaque haemorrhage (59% up to 65%), large lipid core (41% up to 78%), chronic plaque inflammation (71% up to 91%), cap rupture (35% up to 39%), many foam cells (24% up to 43%) and marked vascularity (71% up to 91%) in 23 patients undergoing CEA after 29 days had elapsed. CONCLUSION: Patients undergoing surgery ≤14 days had a significantly higher overall burden of high risk plaque features compared with those undergoing delayed CEA. However, the secondary upsurge across a range of unstable plaque features in patients undergoing CEA after ≥29 days had elapsed suggests that the relationship between recency of symptoms and plaque histology is more complex than had been anticipated in previous studies.

Histologically unstable asymptomatic carotid plaques have altered expression of genes involved in chemokine signalling leading to localised plaque inflammation and rupture.

BACKGROUND: Many studies have evaluated histological and gene expression profiles in TIA/stroke patients after onset of symptoms, but there is limited understanding as to how these plaque related features interact before symptom onset. In particular, no studies have evaluated differential gene expression in histologically unstable (vs stable plaques) in neurologically asymptomatic patients. METHODS: Nine asymptomatic patients had their plaques scored blindly by two independent Histopathologists using the AHA plaque scoring system. RNA extracted from the plaques was hybridised onto a whole genome microarray. Analysis was performed using GenomeStudio (v1.0) and the DAVID bioinformatics resource (v6.7). RESULTS: Three plaques were histologically unstable (Grade 2/3), while six were stable (Grade 0/1). 346 differentially expressed genes (>1.3 fold, P < 0.05) were identified (293 down-regulated and 53 up-regulated) between stable and unstable plaques. Genes related to chemokine and protein signalling (pro-inflammatory/pro-apoptotic) were identified to have high enrichment scores (>1.3) and were significantly up-regulated in unstable (asymptomatic) plaques. CONCLUSION: The findings confirm the intuitively held belief that changes in chemokine and protein signalling may be associated with acute plaque disruption and precede the onset of symptoms. Once validated, these genes could therefore become targets for innovative medical treatments in the future or could help identify asymptomatic patients with histologically unstable plaques that would benefit from surgical intervention.