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.

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.

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.

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.

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.

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 - 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.

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.

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.

Superior two-year results of externally unsupported polyester compared to supported grafts in above-knee bypass grafting: a multicenter randomised trial.

OBJECTIVES: The aim of this study was to compare externally supported thin wall knitted polyester (P-EXS) and externally unsupported thin wall knitted polyester (P-non-EXS) for above-knee (AK) femoro-popliteal bypass grafting. DESIGN: A prospective multicenter randomised clinical trial. MATERIAL AND METHODS: Between 1999 and 2008, 265 AK femoro-popliteal bypass grafts (6 mm in diameter) were performed, including 136 P-EXS and 129 P-non-EXS. The selection of patients was based on the presence of disabling claudication or critical ischaemia. Follow-up took place at 3, 6, 12, 18, and 24 months and included clinical examination and duplex ultrasonography. The main end points of this study were primary patency rates at one and two years. Secondary end points were mortality, and primary assisted and secondary patency rates. Cumulative patency rates were calculated with life-table analysis and log-rank testing. RESULTS: The 1-year primary, primary assisted and secondary patency rates were 65%, 70% and 84%, respectively, for P-EXS and 76% (p = 0.05), 82% (p = 0.03) and 88% (p = 0.35), respectively, for P-non-EXS. Two-year primary, primary assisted and secondary patency rates were 45%, 57% and 70%, respectively, for P-EXS and 62% (p = 0.003), 75% (p = 0.005) and 84% (p = 0.02), respectively, for P-non-EXS. The overall mortality rate after two years was 11.3%. CONCLUSION: In above-knee femoro-popliteal bypass grafting patency rates of externally supported knitted polyester grafts were inferior to their unsupported counterpart. ISRCTN: At the time this study started this number was not the standard.

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.

Type 2 diabetes mellitus is associated with an imbalance in circulating endothelial and smooth muscle progenitor cell numbers.

AIMS/HYPOTHESIS: Individuals with type 2 diabetes mellitus have increased rates of macrovascular disease (MVD). Endothelial progenitor cells (EPCs), circulating angiogenic cells (CACs) and smooth muscle progenitor cells (SMPCs) are suggested to play a role in the pathogenesis of MVD. The relationship between vasoregenerative EPCs or CACs and damaging SMPCs and the development of accelerated MVD in diabetes is still unknown. We tried to elucidate whether EPC, CAC and SMPC numbers and differentiation capacities in vitro differ in patients with and without diabetes or MVD. METHODS: Peripheral blood was obtained from individuals with and without diabetes and MVD (coronary or peripheral artery disease). EPC and SMPC numbers were determined with flow cytometry. Furthermore, CAC and SMPC numbers were quantified after in vitro culture. Their in vitro differentiation capacity was investigated with real-time RT-PCR and quantitative immunofluorescence. RESULTS: In diabetic patients both EPC and CAC levels were reduced (1.3-fold [p < 0.05] and 1.5-fold [p < 0.05], respectively). CAC outgrowth from diabetic patients with MVD was reduced 1.5-fold compared with diabetic patients without MVD (p < 0.05). SMPC levels were similar between diabetic patients and healthy controls. The CAC/SMPC ratio of in vitro cultured progenitor cells was reduced 2.3-fold in samples from diabetic patients (p < 0.001). The differentiation capacity of CACs and SMPCs in vitro remained similar independently of diabetes or MVD. CONCLUSIONS/INTERPRETATION: The ratio between EPCs or CACs and SMPCs is disturbed in type 2 diabetes in favour of SMPCs. This may translate into reduced vascular repair capacity, thereby promoting MVD in type 2 diabetes.

When is supervised exercise therapy considered useful in peripheral arterial occlusive disease? A nationwide survey among vascular surgeons.

OBJECTIVES: Although international guidelines state that supervised exercise therapy (SET) should be offered to all patients with intermittent claudication (IC), SET appears to be underutilised in clinical practice. The aim of this study was to document current opinions of Dutch vascular surgeons on SET as treatment option for peripheral arterial occlusive disease (PAOD). MATERIALS AND METHODS: Vascular surgeons and fellows in vascular surgery were asked to complete a 24-question survey either at the 2011 Annual Meeting of the Dutch Society for Vascular Surgery or online. RESULTS: Ninety-one participants, including 83 vascular surgeons (51% of all Dutch vascular surgeons), completed the survey. The respondents would refer 75.4% of newly diagnosed patients with IC for SET. SET was considered less useful in patients with IC and major (cardiopulmonary) co-morbidity or a significant iliac artery stenosis. In critical limb ischaemia, the combination of SET and angioplasty was considered useful in 71.9%. Respondents regarded patient satisfaction (63.3%) and improvement in pain-free or maximal walking ability (26.6%) as clinically most relevant goals of SET. Most (84.4%) agreed that SET should also include lifestyle management. CONCLUSION: Although the vast majority of Dutch vascular surgeons consider SET as an important treatment option for PAOD, SET should receive more emphasis in clinical practice since arguments not to refer for SET are outdated. Furthermore, vascular surgeons agree that lifestyle management should be integrated in SET.

Prophylactic perioperative anti-thrombotics in open and endovascular abdominal aortic aneurysm (AAA) surgery: a systematic review.

OBJECTIVE: Heparin is used worldwide by vascular surgeons as prophylaxis for arterial thrombo-embolic complications during open and endovascular arterial surgery. Possible harmful effect of heparin use is more perioperative blood loss, resulting in a higher morbidity and mortality. To evaluate the evidence for the use of heparin during aorto-iliac arterial surgery a review was performed. METHODS: A systematic review was performed of literature from MEDLINE, EMBASE and Cochrane databases, last search performed on March 8, 2012. RESULTS: For open surgery for abdominal aortic aneurysm (AAA), only 5 studies were eligible for review and for endovascular aneurysm repair (EVAR) only 1 study. Overall methodological quality of the included studies was poor. One randomised trial could be retrieved. Possible harmful effects of heparin were found of increasing operation time, more blood loss and more transfusion requirements when heparin was used for open AAA surgery in one study. No data were found comparing heparin to no intervention for EVAR. One study compared heparin to a direct thrombin antagonist during EVAR, showing no differences in clinical outcomes. CONCLUSION: Despite limitations this review showed no compelling evidence on the beneficiary effect of the prophylactic perioperative use of heparin during open surgery for (r)AAA. Authors will promote a randomised controlled multi-center trial on this topic for elective open surgical repair of AAA.

B-cell lymphoma related iliac vein occlusion treated by endovenous stent placement.

Unilateral leg swelling is most often caused by deep vein thrombosis but other conditions may mimic this disorder. We describe the case of a patient with symptoms of unilateral lower extremity swelling caused by external compression of the iliac vein by a mass originating from the iliopsoas muscle. Initially this mass was diagnosed as an iliopsoas hematoma in a patient using anticoagulants. However, it proved to be B-cell non-Hodgkin lymphoma. Compression was relieved by placement of an endovenous stent in the left common iliac vein. Endovenous stenting is a relatively new treatment modality that is used to treat post-thrombotic venous occlusions and chronic venous insufficiency. Only a few case series have been described of stenting of compressed pelvic veins by adjacent structures such as gynecological malignancies. Although stent patency lasted only four weeks in this patient, venous stent placement quickly reliefs symptoms and should therefore be considered as an option to bridge time to allow development of sufficient venous collaterals.

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.

Standardised frailty indicator as predictor for postoperative delirium after vascular surgery: a prospective cohort study.

OBJECTIVES: To determine whether the Groningen Frailty Indicator (GFI) has a positive predictive value for postoperative delirium (POD) after vascular surgery. METHODS: Between March and August 2010, 142 consecutive vascular surgery patients were prospectively evaluated. Preoperatively, the GFI was obtained and postoperatively patients were screened with the Delirium Observation Scale (DOS). Patients with a DOS-score ≥3 points were assessed by a geriatrician. Delirium was defined by the DSM-IV-TR criteria. Primary outcome variable was the incidence of POD. Secondary outcome variables were any surgical complication and hospital length of stay (HLOS) (>7 days). RESULTS: Ten patients (7%) developed POD. The highest incidence of POD was found after aortic surgery (17%) and amputation procedures (40%). Increased comorbidities (p = 0.006), GFI score (p = 0.03), renal insufficiency (p = 0.04), elevated C-reactive protein (p = 0.008), high American Society of Anaesthesiologists score (p = 0.05), a DOS-score of ≥3 points (p = 0.001), post-operative intensive care unit admittance (p = 0.01) and HLOS ≥7 days (p = 0.005) were risk factors for POD. The GFI score was not associated with a prolonged HLOS. A mean number of 2 ± 1 (range 0-5) complications were registered. The receiver operator characteristics (ROC) area under the curve for the GFI was 0.70. CONCLUSIONS: The GFI can be helpful in the early identification of POD after vascular surgery in a select group of high-risk patients.

Myocardial perfusion reserve compared with peripheral perfusion reserve: a [13N]ammonia PET study.

INTRODUCTION: [13N]ammonia PET allows quantification of myocardial perfusion. The similarity between peripheral flow and myocardial perfusion is unclear. We compared perfusion flow in the myocardium with the upper limb during rest and adenosine stress [13N]ammonia PET to establish whether peripheral perfusion reserve (PPR) correlates with MPR. METHODS: [13N]ammonia myocardial perfusion PET-scans of 58 patients were evaluated (27 men, 31 women, age 64 ± 13 years) and were divided in four subgroups: patients with coronary artery disease (CAD, n = 15), cardiac syndrome X (SX, n = 14), idiopathic dilating cardiomyopathy (DCM, n = 16), and normal controls (NC, n = 13). Peripheral limb perfusion was measured in the muscular tissue of the proximal upper limb and quantified through a 2-tissue-compartment model and the PPR was calculated (stress/rest ratio). MPR was also calculated by a 2-tissue-compartment model. The PPR results were compared with the MPR findings. RESULTS: Mean myocardial perfusion increased significantly in all groups as evidenced by the MPR (CAD 1.99 ± 0.47; SX 1.39 ± 0.31; DCM 1.72 ± 0.69; NC 2.91 ± 0.78). Mean peripheral perfusion also increased but not significantly and accompanied with great variations within and between groups (mean PPR: CAD 1.30 ± 0.79; SX 1.36 ± 0.71; DCM 1.60 ± 1.22; NC 1.27 ± 0.63). The mean difference between PPR and MPR for all subpopulations varied widely. No significant correlations in flow reserve were found between peripheral and myocardial microcirculatory beds in any of the groups (Total group: r = -0.07, SEE = 0.70, CAD: r = 0.14, SEE = 0.48, SX: r = 0.17, SEE = 0.30, DCM: r = -0.11, SEE = 0.71, NC: r = -0.19, SEE = 0.80). CONCLUSION: No correlations between myocardial and peripheral perfusion (reserve) were found in different patient populations in the same PET session. This suggests a functional difference between peripheral and myocardial flow in the response to intravenously administered adenosine stress.

[Results of endovascular repair of TAAA in the first 50  patients]. / Bericht über die ersten 50 endovaskulären thorako-abdominellen Behandlungen mit Seitenarmprothesen.

BACKGROUND: Developments with fenestrated and branched stent grafts have opened the way to treat complex aortic aneurysms involving the visceral arteries. First reports on endovascular treatment of thoracoabdominal aneurysms have demonstrated the feasibility of the technique. METHODS: A literature review and results of first 50  patients treated with a custom-made Zenith device with fixed branches are presented. Most of the patients were refused open surgery mainly for the extent of the disease combined with co-morbidity, which included in most patients a combination of several risk factors. Mean aneurysm size was 71 mm and extent of the aneurysm was type  I (n = 9), type  II (n = 13), type  III (n = 19), and type  IV (n = 9), respectively. RESULTS: Primary and primary assisted technical successes in our series were 88 % (44 / 50) and 92 % (46 / 50), respectively. One patient died on day  1 from an intraoperative aneurysm rupture. In two patients a renal artery was lost, one due to rupture and one due to malpositioning of the bridging stent graft. In a fourth patient, a celiac artery could not be catheterised and was lost. Finally, in two more patients, catheterisation of in total three renal arteries proved impossible. This was solved by a retrograde approach for two renal arteries via laparotomy in one patient, and a spleno-renal bypass in the other patient. Thirty-day mortality was 8 %. Estimated survival at 6  months, 1  year, and 2  years was 91.2 %, 79.8 %, and 69.7 %, respectively. Freedom of reintervention of all kinds at 1 and 2  years was 81.9 % and 73.7 %, respectively. CONCLUSION: Results of fully endovascular repair of thoracoabdominal aneurysms in a high-risk cohort are promising. A learning curve should be expected. Although longer term results need to be awaited, it is likely that endovascular repair of thoracoabdominal aneurysms will become a preferential treatment option for many patients in the future.