CYP2C19 genotype-guided antithrombotic treatment versus conventional clopidogrel therapy in peripheral arterial disease: study design of a randomized controlled trial (GENPAD).

BACKGROUND: Clopidogrel is recommended in international guidelines to prevent arterial thrombotic events in patients with peripheral arterial disease (PAD). Clopidogrel itself is inactive and metabolism is dependent on the CYP2C19 enzyme. About 30% of Caucasian PAD patients receiving clopidogrel carry 1 or 2 CYP2C19 loss-of-function allele(s) and do not or to a limited extent convert the prodrug into its active metabolite. As a result, platelet inhibition may be inadequate which could lead to an increased risk of adverse clinical events related to arterial thrombosis. A CYP2C19 genotype-guided antithrombotic treatment might be beneficial for PAD patients. METHODS: GENPAD is a multicenter randomized controlled trial involving 2,276 PAD patients with an indication for clopidogrel monotherapy. Patients with a separate indication for dual antiplatelet therapy or stronger antithrombotic therapy are not eligible for study participation. Patients randomized to the control group will receive clopidogrel 75 mg once daily without pharmacogenetic guidance. Patients randomized to the intervention group will be tested for carriage of CYP2C19 *2 and *3 loss-of-function alleles, followed by a genotype-guided antithrombotic treatment with either clopidogrel 75 mg once daily for normal metabolizers, clopidogrel 150 mg once daily for intermediate metabolizers, or acetylsalicylic acid 80 mg once daily plus rivaroxaban 2.5 mg twice daily for poor metabolizers. The primary outcome is a composite of myocardial infarction, ischemic stroke, cardiovascular death, acute or chronic limb ischemia, peripheral vascular interventions, or death. The secondary outcomes are the individual elements of the primary composite outcome and clinically relevant bleeding complications. CONCLUSION: The aim of the GENPAD study is to evaluate the efficacy, safety, and cost-effectiveness of a genotype-guided antithrombotic treatment strategy compared to conventional clopidogrel treatment in PAD patients.

Nutritional status and out-of-hospital mortality in vascular surgery patients.

BACKGROUND: Malnutrition is often present in vascular surgery patient during hospital admission. The present evidence of the consequence malnutrition has on morbidity and mortality is limited. AIM: The purpose of this study was to determine the effect of nutritional status on out-of-hospital mortality in vascular surgery patients. METHODS: An observational cohort study was performed, studying non-cardiac vascular surgery patients surviving hospital admission 18 years or older treated in Boston, Massachusetts, USA. The exposure of interest was nutritional status categorized as well nourished, at-risk for malnutrition, nonspecific malnutrition or protein-energy malnutrition. The all cause 90-day mortality following hospital discharge was the primary outcome. Adjusted odds ratios were estimated by multivariable logistic regression models. RESULTS: This cohort included 4432 patients comprised of 48% women and a mean age 61.7 years. After evaluation by a registered dietitian, 3819 patients were determined to be well nourished, 215 patients were at-risk for malnutrition, 351 had non-specific malnutrition and 47 patients had protein-energy malnutrition. After adjustment for age, sex, ethnicity, medical versus surgical Diagnosis Related Group type, Deyo-Charlson index, length of stay, and vascular Current Procedural Terminology code category, the 90-day post-discharge mortality odds ratio for patients with non-specific malnutrition OR 1.96 (95%CI 1.21, 3.17) and for protein-energy malnutrition OR 3.58 (95%CI 1.59, 8.06), all relative to patients without malnutrition. DISCUSSION: Nutritional status is a strong predictor of out-of-hospital mortality. This suggests that patient with vascular disease suffering from malnutrition could benefit from more intensified In-hospital and out-of-hospital dietary guidance and interventions.

Increased frequency of proangiogenic tunica intima endothelial kinase 2 (Tie2) expressing monocytes in individuals with type 2 diabetes mellitus.

BACKGROUND: Individuals with type 2 diabetes mellitus (T2DM) have an increased risk for developing macrovascular disease (MVD) manifested by atherosclerosis. Phenotypically and functionally different monocyte subsets (classical; CD14++CD16-, non-classical; CD14+CD16++, and intermediate; CD14++CD16+) including pro-angiogenic monocytes expressing Tie2 (TEMs) can be identified. Here we investigated monocyte heterogeneity and its association with T2DM and MVD. METHODS: Individuals with (N = 51) and without (N = 56) T2DM were recruited and allocated to "non-MVD" or "with MVD" (i.e., peripheral or coronary artery disease) subgroups. Blood monocyte subsets were quantified based on CD14, CD16 and Tie2 expression levels. Plasma levels of Tie2-ligands angiopoietin-1 and angiopoietin-2 were determined using ELISA. Carotid endarterectomy samples from individuals with (N = 24) and without (N = 22) T2DM were stained for intraplaque CD68+ macrophages (inflammation) and CD34+ (angiogenesis), as plaque vulnerability markers. RESULTS: Monocyte counts were similar between individuals with T2DM and healthy controls (non-diabetic, non-MVD). Non-classical monocytes were reduced (p < 0.05) in T2DM, whereas the percentage of TEMs within the intermediate subset was increased (p < 0.05). T2DM was associated with increased angiopoietin-1 (p < 0.05) and angiopoietin-2 (p = 0.0001) levels. Angiopoietin-2 levels were higher in T2DM individuals with MVD compared with non-MVD (p < 0.01). Endarterectomized plaques showed no differences in macrophage influx and microvessel number between individuals with and without T2DM. CONCLUSIONS: Monocyte subset distribution is altered in T2DM with reduced non-classical monocytes and increased TEM percentage in the intermediate monocyte subset. Increased angiopoietin-2 levels together with increased frequency of TEMs might promote plaque vulnerability in T2DM which could however not be confirmed at tissue level in advanced atherosclerotic lesions.

Inguinal microbiome in patients undergoing an endovascular aneurysm repair: Application of next-generation sequencing of the 16S-23S rRNA regions.

BACKGROUND: Surgical site infection (SSI) remains a hazardous complication after vascular surgery. In this pilot study we investigated the inguinal microbiome in skin biopsies using histology and 16S-23S rDNA Next Generation Sequencing (NGS). Our hypothesis was that causative microorganisms of SSI are present in the inguinal microbiome. METHODS: Data on surgical site infections and skin samples from the Percutaneous in Endovascular Repair versus Open (PiERO) trail were evaluated. Two patients with SSI were matched for age and comorbidity to eight matching patients of the PiERO trial. All patients were treated for an abdominal aortic aneurysm with endovascular repair. Nasal and perineal cultures were taken preoperatively to detect Staphylococcus aureus carriage. After disinfection with chlorhexidine, groin biopsies were taken to identify bacteria in deeper skin layers. All samples were subjected to histological analysis and culture-free 16S-23S rDNA NGS. RESULTS: Staphylococcus aureus species were cultured in 5 out of 20 preoperative nasal and perineal swaps. Histology detected only a few bacteria. NGS of the 16S-23S rRNA regions identified DNA of bacterial species in all biopsies (20/20). Most identified genera and species proved to be known skin flora bacteria. No relation was found between SSIs and the preoperative microbiome. CONCLUSION: In this pilot study, an innovative analysis of the preoperative microbiome using 16S-23S rDNA NGS did not show a relation with the occurrence of a surgical site infection. No pathogenic bacterial species were present in the inguinal skin after disinfection with chlorhexidine.

Eosinopenia and post-hospital outcomes in critically ill non-cardiac vascular surgery patients.

BACKGROUND AND AIMS: Eosinopenia is a marker for acute inflammation. We hypothesized that eosinopenia at Intensive Care Unit (ICU) admission in vascular surgery patients who receive critical care, would be associated with increased mortality following hospital discharge. METHODS AND RESULTS: We performed a two-center observational cohort study of critically ill, non-cardiac adult vascular surgery patients who received treatment in Boston between 1997 and 2012 and survived hospital admission. The consecutive sample included 5083 patients (male 57%, white 82%, mean age [SD] 61.6 [17.4] years). The exposure was Absolute eosinophil count measured within 24 h of admission to the ICU and categorized as ≤10 cells/µL, 11-50 cells/µL, 51-100 cells/µL, 101-350 cells/µL (normal range), and >350 cells/µL. The primary outcome was all-cause mortality within 90 days of hospital discharge. The secondary outcome was discharge to home following hospitalization. 90-day post-discharge mortality was 6.7%, and 12.9% of patients were readmitted within 30 days. After multivariable adjustment, patients with eosinopenia (≤10 cells/µL) have a 90-day post-discharge mortality OR of 1.97 (95%CI 1.42, 2.73; P < 0.001) relative to patients with an absolute eosinophil count of 101-350 cells/µL. Further, after multivariable adjustment, patients with eosinopenia (≤10 cells/µL) have a 25% lower odds of discharge to home compared to patients with an absolute eosinophil count of 101-350 cells/µL [OR = 0.71 (CI 95% 0.59-0.85); P < 0.001]. CONCLUSION: Eosinopenia at ICU admission is a robust predictor of increased mortality and lower likelihood of discharge to home in vascular surgery patients treated with critical care who survive hospitalization.

18F-sodium fluoride positron emission tomography assessed microcalcifications in culprit and non-culprit human carotid plaques.

BACKGROUND: 18F-NaF positron emission tomography (PET) targets microcalcifications. We compared in vitro microPET assessed 18F-NaF uptake between culprit and non-culprit human carotid plaques. Furthermore, we compared 18F-NaF uptake with calcification visualized on microcomputed tomography (microCT). METHODS: Carotid plaques from stroke patients undergoing surgery were incubated in 18F-NaF and scanned using a microPET and a microCT scan. The average PET assessed 18F-NaF uptake was expressed as percentage of the incubation dose per gram (%Inc/g). 18F-NaF PET volume of interest (VOI) was compared with CT calcification VOI. RESULTS: 23 carotid plaques (17 culprit, 6 non-culprit) were included. The average 18F-NaF uptake in culprit carotid plaques was comparable with the uptake in non-culprit carotid plaques (median 2.32 %Inc/g [IQR 1.98 to 2.81] vs. median 2.35 %Inc/g [IQR 1.77 to 3.00], P = 0.916). Only a median of 10% (IQR 4 to 25) of CT calcification VOI showed increased 18F-NaF uptake, while merely a median of 35% (IQR 6 to 42) of 18F-NaF PET VOI showed calcification on CT. CONCLUSIONS: 18F-NaF PET represents a different stage in the calcification process than CT. We observed a similar PET assessed 18F-NaF uptake and pattern in culprit and non-culprit plaques of high-risk patients, indicating that this method may be of more value in early atherosclerotic stenosis development.

Decision making process for amputation in case of therapy resistant complex regional pain syndrome type-I in a Dutch specialist centre.

Deciding for an amputation in case of complex regional pain syndrome type I (CRPS-I) is controversial. Evidence for favorable or adverse effects of an amputation is weak. We therefore follow a careful and well-structured decision making process. After referral of the patient with the request to amputate the affected limb, it is checked if the diagnosis CRPS-I is correct, duration of complaints is more than 1 year, all treatments described in the Dutch guidelines have been tried and if consequences of an amputation have been well considered by the patient. Thereafter the patient is assessed by a multidisciplinary team (psychologist, physical therapist, anesthesiologist-pain specialist, physiatrist and vascular surgeon). During a multidisciplinary meeting professionals summarize their assessment. Pros and cons of an amputation are discussed, taking into account level of amputation and expectations about post amputation functioning of patient and team. Based on assessments and discussion a consensus based decision is formulated and the patient is informed. If it is decided that an amputation is to be performed, the amputation will follow shortly. If it is decided not to amputate, the decision is extensively explained to the patient. Incidence of patients suffering from therapy resistant CRPS-I referred for amputation is low and because referred patients are strongly in favor of an amputation, a randomized controlled trial will be difficult to perform. Hence level of evidence in favor or against an amputation will remain low. We therefore report our decision making process to facilitate discussion about this difficult and delicate matter.

Diverging effects of diabetes mellitus in patients with peripheral artery disease and abdominal aortic aneurysm and the role of advanced glycation end-products: ARTERY study - protocol for a multicentre cross-sectional study.

INTRODUCTION: Diabetes mellitus is a well-defined risk factor for peripheral artery disease (PAD), but protects against the development and growth of abdominal aortic aneurysm (AAA). Diabetes mellitus is associated with arterial stiffening and peripheral arterial media sclerosis. Advanced glycation end-products (AGEs) are increased in diabetes mellitus and cardiovascular disease. AGEs are known to form cross-links between proteins and are associated with arterial stiffness. Whether AGEs contribute to the protective effects of diabetes mellitus in AAA is unknown. Therefore, the ARTERY (Advanced glycation end-pRoducts in patients with peripheral arTery disEase and abdominal aoRtic aneurYsm) study is designed to evaluate the role of AGEs in the diverging effects of diabetes mellitus on AAA and PAD. METHODS AND ANALYSIS: This cross-sectional multicentre study will compare the amount, type and location of AGEs in the arterial wall in a total of 120 patients with AAA or PAD with and without diabetes mellitus (n=30 per subgroup). Also, local and systemic vascular parameters, including pulse wave velocity, will be measured to evaluate the association between arterial stiffness and AGEs. Finally, AGEs will be measured in serum, urine, and assessed in skin with skin autofluorescence using the AGE Reader. ETHICS AND DISSEMINATION: This study is approved by the Medical Ethics committees of University Medical Center Groningen, Martini Hospital and Medisch Spectrum Twente, the Netherlands. Study results will be disseminated through peer-reviewed journals and scientific events. TRIAL REGISTRATION NUMBER: trialregister.nl NTR 5363.

Editor's Choice - Arteriotomy Closure Devices in EVAR, TEVAR, and TAVR: A Systematic Review and Meta-analysis of Randomised Clinical Trials and Cohort Studies.

OBJECTIVES: Cardiac and vascular surgery benefit from percutaneous interventions. Arteriotomy closure devices (ACDs) enable minimally invasive access to the common femoral artery (CFA). The objective of this review was to assess the differences between ACDs and surgical cut down (SCD) of the CFA regarding the number of complications, duration of surgery (DOS), and hospital length of stay (HLOS). DESIGN: A systematic literature search with predefined search terms was performed using MEDLINE, Embase, and the Cochrane Library (2000-2016). All studies reporting on ACD and SCD for a puncture of the CFA of at least 12 French (Fr.) were assessed for eligibility. METHODS: Included were randomised controlled trials and cohort studies comparing both techniques. Patient characteristics, exclusion criteria, and conversion rates were evaluated. Complications, DOS, and HLOS were compared. MATERIALS: A total of 17 studies were included for meta-analysis, describing 7889 vascular access sites; four studies were randomised trials, two studies reported from a prospective database, and 11 studies reported retrospective cohorts. RESULTS: ACD was associated with fewer post-operative seromas (odds ratio [OR] 0.15, 95% confidence interval [CI] 0.06-0.35), less wound dehiscence (OR 0.14, 95% CI 0.03-0.78), and fewer surgical site infections (OR 0.38, 95% CI 0.23-0.63). Post-operative pseudoaneurysms were significantly more common in the ACD group (OR 3.83, 95% CI 1.55-9.44). In five of 17 studies, DOS and HLOS were not reduced in the ACD group. When all studies reporting a mean DOS and/or HLOS were compared in a non-parametric analysis, neither was significantly different. CONCLUSION: This meta-analysis favours ACD regarding the number of wound complications compared with SCD in endovascular aneurysm repair, thoracic endovascular aneurysm repair, and transcatheter aortic valve repair. Treatment duration (DOS and HLOS) was not reduced in ACD. The differences are of limited clinical significance and with this equivocal quality of evidence, the ACD may be considered safe for CFA access in suitable patients.

Development and External Validation of a Model Predicting Death After Surgery in Patients With a Ruptured Abdominal Aortic Aneurysm: The Dutch Aneurysm Score.

OBJECTIVE: The decision whether or not to proceed with surgical intervention of a patient with a ruptured abdominal aortic aneurysm (rAAA) is very difficult in daily practice. The primary objective of the present study was to develop and to externally validate a new prediction model: the Dutch Aneurysm Score (DAS). METHODS: With a prospective cohort of 10 hospitals (n = 508) the DAS was developed using a multivariate logistic regression model. Two retrospective cohorts with rAAA patients from two hospitals (n = 373) were used for external validation. The primary outcome was the combined 30 day and in-hospital death rate. Discrimination (AUC), calibration plots, and the ability to identify high risk patients were compared with the more commonly used Glasgow Aneurysm Score (GAS). RESULTS: After multivariate logistic regression, four pre-operative variables were identified: age, lowest in hospital systolic blood pressure, cardiopulmonary resuscitation, and haemoglobin level. The area under the receiver operating curve (AUC) for the DAS was 0.77 (95% CI 0.72-0.82) compared with the GAS with an AUC of 0.72 (95% CI 0.67-0.77). The DAS showed a death rate in patients with a predicted death rate ≥80% of 83%. CONCLUSIONS: The present study shows that the DAS has a higher discriminative performance (AUC) compared with the GAS. All clinical variables used for the DAS are easy to obtain. Identification of low risk patients with the DAS can potentially reduce turndown rates. The DAS can reliably be used by clinicians to make a more informed decision in dialogue with the patient and their family whether or not to proceed with surgical intervention.

Cystathionine γ-lyase is expressed in human atherosclerotic plaque microvessels and is involved in micro-angiogenesis.

Atherosclerotic plaques are classically divided into stable and vulnerable plaques. Vulnerable plaques are prone to rupture with a risk for infarction. High intraplaque microvessel density predisposes to plaque vulnerability. Hydrogen sulfide (H2S) is a proangiogenic gasotransmitter which is endogenously produced by cystathionine γ-lyase (CSE), and is believed to have vasculoprotective effects. However, due to its proangiogenic effects, H2S may result in pathological angiogenesis in atherosclerotic plaques, thereby increasing plaque vulnerability. The aim of this study was to determine CSE expression pattern in atherosclerotic plaques, and investigate whether CSE is involved in micro-angiogenesis in vitro. Endarterectomy plaques were studied for CSE expression, and the role of CSE in micro-angiogenesis was studied in vitro. CSE is expressed in plaques with similar levels in both stable and vulnerable plaques. CSE co-localized with von Willebrand Factor-positive microvessel endothelial cells and alpha-smooth-muscle actin-positive SMCs. In vitro, inhibition of CSE in HMEC-1 reduced tube formation, cell viability/proliferation, and migration which was restored after culture in the presence of H2S donor GYY4137. CSE is expressed in intraplaque microvessels, and H2S is a stimulator of micro-angiogenesis in vitro. Due to this pro-angiogenic effect, high levels of CSE in atherosclerotic plaques may be a potential risk for plaque vulnerability.

Clinical Outcome of Isolated Popliteal Artery Aneurysms Treated with a Heparin-bonded Stent Graft.

OBJECTIVE: The use of self-expanding stent grafts for treatment of popliteal artery aneurysms (PAA) is a matter of debate, although several studies have shown similar results compared with open surgery. In recent years, a new generation stent graft, with heparin-bonding technology, became available. The aim of this study is to present the results of endovascular PAA repair with heparin-bonded stent grafts. METHODS: Data on all patients with PAA treated with a heparin-bonded polytetrafluoroethylene (ePTFE) stent graft between April 2009 and March 2014 were gathered in a database and retrospectively analyzed. Data were collected from four participating hospitals. Standard follow-up consisted of clinical assessment, and duplex ultrasound at 6 weeks, 6 months, 12 months, and annually thereafter. The primary endpoint of the study was primary patency. Secondary endpoints were primary-assisted and secondary patency and limb salvage rate. RESULTS: A total of 72 PAA was treated in 70 patients. Mean age was 71.2 ± 8.5 years and 93% were male (n = 65). The majority of PAA were asymptomatic (78%). Sixteen cases (22%) had a symptomatic PAA, of which seven (44%) presented with acute ischemia. Early postoperative complications occurred in two patients (3%). Median follow-up was 13 months (range 0-63 months). Primary patency rate at 1 year was 83% and after 3 years 69%; primary assisted patency rate was 87% at 1 year and 74% after 3 years. Secondary patency rate was 88% and 76% at 1 and 3 years, respectively. There were no amputations during follow-up. CONCLUSION: Endovascular treatment of PAA with heparin-bonded stent grafts is a safe treatment option with good early and mid-term patency rates comparable with open repair using the great saphenous vein.

Editor's Choice--First Results of the Covered Endovascular Reconstruction of the Aortic Bifurcation (CERAB) Technique for Aortoiliac Occlusive Disease.

OBJECTIVE: In this study the first results are presented of a new endovascular technique using covered stents to reconstruct the aortic bifurcation in patients with aortoiliac occlusive disease. With the "Covered Endovascular Reconstruction of the Aortic Bifurcation" (CERAB) technique, the anatomy and physiology of the aortic bifurcation is mimicked. MATERIAL AND METHODS: Between 2009 and March 2014, 103 patients (51 male, 52 female) suffering from obstructive lesions at the level of the aortic bifurcation were treated with CERAB in two clinics. The median age was 61 years (range 36-85 years). Lesion morphology was evaluated by CT angiography. Six TASC-II B lesions, nine TASC-II C lesions, and 88 TASC-II D lesions were treated. Follow up was a median 12 months (range 0-49 months) and consisted of clinical examination, ankle brachial indices, and duplex ultrasound examination. RESULTS: Technical success was obtained in 98 procedures (95.1%). In five cases lesions could not be recanalized. Primary patency was 87.3% at 1 year and 82.3% at 2 years, while secondary patency was 95.0% at 1 year and 95.0% at 2 years. Mean ankle brachial indices improved significantly from 0.64 ± 0.21 before to 0.91 ± 014, after the procedure (p < .001). The overall 30 day complication rate was 23.3%, including 22 minor complications and two major complications (1.9%). There was no 30 day mortality. Median hospital stay was 2 days (range 1-16 days). CONCLUSIONS: The CERAB technique appears to be a safe and feasible alternative to open surgical reconstruction of the aortic bifurcation in complex occlusive disease. Comparative studies with the current gold standards are indicated.

Editor's Choice - Ten-year Experience with Endovascular Repair of Thoracoabdominal Aortic Aneurysms: Results from 166 Consecutive Patients.

OBJECTIVE: To present a 10 year experience with endovascular thoracoabdominal aortic aneurysm (TAAA) repair using fenestrated and branched stent grafts. MATERIALS AND METHODS: Consecutive patients with TAAA treated with fenestrated and branched stent grafts within the period January 2004-December 2013. Data were collected prospectively. RESULTS: 166 patients (125 male, 41 female, mean age 68.8 ± 7.6 years) were treated. The mean TAAA diameter was 71 ± 9.3 mm. Types of TAAA were: type I, n = 12 (7.2%), type II, n = 50 (30.1%), type III, n = 53 (31.9%), type IV, n = 41 (24.8%), and type V, n = 10 (6%). Fifteen (9%) patients had an acute TAAA (11 contained rupture, 4 symptomatic). One hundred and eight (65%) patients were refused for open surgery earlier. Seventy eight (47%) patients had previously undergone one or more open/endovascular aortic procedures. Technical success was 95% (157/166). Thirty day operative mortality was 7.8% (13/166), with an in hospital mortality of 9% (15/166). Peri-operative spinal cord ischemia (SCI) was observed in 15 patients (9%), including permanent paraplegia in two (1.2%). Mean follow up was 29.2 ± 21 months. During follow up 40 patients died, two of them probably from aneurysm related cause. Re-intervention, mostly by endovascular means, was needed in 40 (24%) patients. Estimated survival at 1, 2, and 5 years was 83% ± 3%, 78% ± 3.5%, and 66.6% ± 6.1%, respectively. Estimated target vessel stent patency at 1, 2, and 5 years was 98% ± 0.6%, 97% ± 0.8%, and 94.2% ± 1.5%, respectively. Estimated freedom from re-intervention at 1 and 3 years was 88.3% ± 2.7%, and 78.4% ± 4.5%, respectively. CONCLUSIONS: Endovascular repair of TAAA with fenestrated and branched stent grafts in high volume centers appears safe and effective in the mid-term in a high risk patient cohort. A considerable reintervention rate should be acknowledged, however.

Prophylactic intraoperative antithrombotics in open infrainguinal arterial bypass surgery: a systematic review.

Unfractionated heparin (UFH) is used intraoperatively as antithrombotic by most vascular surgeons worldwide during infrainguinal bypass surgery (IABS) to reduce the risk of peroperative and early graft thrombosis. To reduce the harmful side effects of UFH (bleeding complications, HIT) and to reduce peroperative and early graft failure, other pharmaceuticals have been suggested for IABS. A systematic review was performed using MEDLINE, EMBASE and Cochrane databases. Only 9 studies on IABS and intraoperative antithrombotic use were eligible for review. Between studies heterogeneity was high and investigated study populations were often of small size. No study was retrieved comparing UFH to no-UFH. Dextran, human antithrombin and iloprost showed no beneficial effect compared to UFH alone for patency, mortality and morbidity. Low molecular weight heparin (LMWH) has potential benefits compared to UFH, but a statistically significant effect could not be demonstrated from the current review. The use of UFH during IABS to prevent intraoperative graft thrombosis has not been proven in randomized clinical trials. Dextran, human antithrombin and iloprost showed to be of no added beneficial effect for the patient compared to UFH alone. Data on the use of LMWH instead of UFH are promising, but no statistically significant benefit could be reproduced from literature. Results from a recent Cochrane review were favourable for LMWH, but it appeared that included data were not complete in that review. Randomized controlled trials are required for intra-operative use of antithrombotics and to improve peroperative and early patency after IABS.

Perioperative prophylactic antithrombotic strategies in vascular surgery: current practice in the Netherlands.

AIM: The aim of this study was to evaluate the current practice of the use of perioperative antithrombotic drugs to prevent arterial thrombo-embolic complications during arterial vascular surgery by Dutch vascular surgeons. Aim was also to compare the results with the literature and to evaluate the effect of guidelines. METHODS: A comprehensive questionnaire was sent to all Dutch vascular surgeons performing arterial reconstructive surgery. RESULTS: The response rate was 84%. Acetylsalicylic acid (ASA) was continued perioperatively by most surgeons (91%). Clopidogrel was discontinued by the majority of respondents (65%). During operation 97% of surgeons administered unfractionated heparin (UFH) before arterial clamping. A minority (11%) measures peroperatively anticoagulant activity in patients' blood. After infrainguinal venous bypass most surgeons (81%) preferred monotherapy with vitamin K antagonists (VKA), in agreement with the Dutch guideline in this respect. Before the introduction of the guideline in 2005, a survey was performed in 2004. Results of our 2011 survey showed more respondents (6% to 11%) prescribed ASA or VKA according to these guidelines. CONCLUSION: This survey showed a recognizable pattern of variation for perioperative arterial thrombosis prophylaxis amongst Dutch vascular surgeons, in agreement with reports from other countries over the past 20 years. Although a higher percentage of surgeons complied in 2011 with existing guidelines than in 2004, guidelines were not completely met. Possibly because current guidelines are not fully supported by evidence and do not cover all aspects of perioperative arterial thrombosis prophylaxis. Clearly there is need for (more) convincing data based on RCT's concerning the various aspects of perioperative arterial thrombosis prophylaxis.

Mesenteric ischemia after abdominal aortic aneurysm repair: a systemic review.

Mesenteric ischemia after abdominal aneurysm repair is a devastating complication with mortality rates up to 70%. Incidence however is relatively low. The aim of this review was to provide an overview on current insights, diagnostic modalities and on mesenteric ischemia after abdominal aortic aneurysm repair.

Cost-effectiveness and cost-utility of endovascular versus open repair of ruptured abdominal aortic aneurysm in the Amsterdam Acute Aneurysm Trial.

BACKGROUND: Minimally invasive endovascular aneurysm repair (EVAR) could be a surgical technique that improves outcome of patients with ruptured abdominal aortic aneurysm (rAAA). The aim of this study was to analyse the cost-effectiveness and cost-utility of EVAR compared with standard open repair (OR) in the treatment of rAAA, with costs per 30-day and 6-month survivor as outcome parameters. METHODS: Resource use was determined from the Amsterdam Acute Aneurysm (AJAX) trial, a multicentre randomized trial comparing EVAR with OR in patients with rAAA. The analysis was performed from a provider perspective. All costs were calculated as if all patients had been treated in the same hospital (Onze Lieve Vrouwe Gasthuis, teaching hospital). RESULTS: A total of 116 patients were randomized. The 30-day mortality rate was 21 per cent after EVAR and 25 per cent for OR: absolute risk reduction (ARR) 4·4 (95 per cent confidence interval (c.i.) -11·0 to 19·7) per cent. At 6 months, the total mortality rate for EVAR was 28 per cent, compared with 31 per cent among those assigned to OR: ARR 2·4 (-14·2 to 19·0) per cent. The mean cost difference between EVAR and OR was €5306 (95 per cent c.i. -1854 to 12,659) at 30 days and €10,189 (-2477 to 24,506) at 6 months. The incremental cost-effectiveness ratio per prevented death was €120,591 at 30 days and €424,542 at 6 months. There was no significant difference in quality of life between EVAR and OR. Nor was EVAR superior regarding cost-utility. CONCLUSION: EVAR may be more effective for rAAA, but its increased costs mean that it is unaffordable based on current standards of societal willingness-to-pay for health gains.

Calcification as a risk factor for rupture of abdominal aortic aneurysm.

OBJECTIVES: Abdominal aortic aneurysm (AAA) is a major cause of death in developed countries. The AAA diameter is still the only validated prognostic measure for rupture, and therapeutic interventions are initiated accordingly. This still leads to unnecessary interventions in some cases or unidentified impending ruptures. Vascular calcification has been validated abundantly as a risk factor in the cardiovascular field and may strengthen the rupture risk assessment of the AAA. With this study we aim to assess the correlation between AAA calcification and rupture risk in a retrospective unmatched case-control population. METHODS: A database of 334 AAA patients was evaluated. Three groups were formed: elective (eAAA; n = 233), ruptured (rAAA; n = 73) and symptomatic non-ruptured (sAAA; n = 28) AAA patients. The Abdominal Aortic Calcification-8 score (AAC-8) was used to measure the severity of vascular calcification. RESULTS: The AAA diameter (61 ± 12 mm vs. 74 ± 21 mm; p < .001) and AAC-8 score (3.4 ± 2 points vs. 4.9 ± 2.3 points; p < .001) of the eAAA and the combined rAAA and sAAA groups, respectively, were significantly different after univariate analysis. Multivariate analysis showed that larger AAA diameter (odds ratio [OR]: 1.048/mm increase; 95% confidence interval [CI]: 1.042-1.082; p < .001) and a higher AAC-8 score (OR: 1.34/point increase; 95% CI: 1.19-1.53; p < .001) were significantly associated with development into a sAAA or rAAA. Peripheral artery disease was significantly correlated to eventual elective treatment (OR: 0.39; 95% CI: .15-1; p = .049). CONCLUSION: This study suggests a trend of an increased degree of calcification in symptomatic or even ruptured AAA patients compared with elective AAA patients.

New insights in (acute) endovascular abdominal aneurysm repair: when fenestrated devices fall short.

The suitability for endovascular aneurysm repair (EVAR) is determined primarily by abdominal aortic aneurysm (AAA) anatomy. For patients unsuitable for standard EVAR, due to proximal neck anatomy, fenestrated aortic stent-grafting (FEVAR) is a viable alternative to open repair surgery. Initially FEVAR stent-grafts were custom-made to fit the unique anatomical characteristics of each treated individual. This customization leads to production delays therefore excluding acute aneurysms from endovascular treatment. For patients in need for more urgent treatment, several alternatives have currently been developed. The aim of this review is to provide an overview on current developments and results in acute endovascular abdominal aortic aneurysm repair.