The Dutch chronic lower limb-threatening ischemia registry (THRILLER): A study protocol for popliteal and infrapopliteal endovascular interventions.

INTRODUCTION: Chronic limb-threatening ischemia (CLTI) is the end stage of peripheral arterial disease (PAD) and is associated with high amputation rates, mortality and disease-related health care costs. In infrapopliteal arterial disease (IPAD), endovascular revascularization should be considered for the majority of anatomical and clinical subgroups of CLTI. However, a gap of high-quality evidence exists in this field. The aim of the Dutch Chronic Lower Limb-Threatening Ischemia Registry (THRILLER) is to collect real world data on popliteal and infrapopliteal endovascular interventions. METHODS: THRILLER is a clinician-driven, prospective, multicenter, observational registry including all consecutive patients that undergo a popliteal or infrapopliteal endovascular intervention in seven Dutch hospitals. We estimate that THRILLER will include 400-500 interventions annually. Standardized follow-up visits with wound monitoring, toe pressure measurement and duplex ultrasonography will be scheduled at 6-8 weeks and 12 months after the intervention. The independent primary endpoints are primary patency, limb salvage and amputation free survival. Patients must give informed consent before participation and will be included according to predefined reporting standards. A data log of patients who meet the inclusion criteria but are not included in the registry will be maintained. We intend to conduct the first interim analysis two years after the start of inclusion. The results will be published in a scientific journal. DISCUSSION: Despite innovations in medical therapy and revascularization techniques, patients with CLTI undergoing endovascular revascularization still have a moderate prognosis. Previous prospective cohort studies were hampered by small sample sizes or heterogeneous reporting. Randomized controlled trials (RCTs) have high costs, potential conflicts of interest and give a limited reflection of daily practice. THRILLER aims to provide the largest prospective well phenotyped up-to-date dataset on treatment outcomes in CLTI patients to answer multiple underexplored research questions regarding diagnostics, medication, patient selection, treatment strategies and post intervention follow-up.

Short-term outcome and mid-term access site complications of the percutaneous approach to endovascular abdominal aortic aneurysm repair (PEVAR) after introduction in a vascular teaching hospital.

The objective is to evaluate our center's experience with the safety and efficacy of the percutaneous approach to endovascular abdominal aortic aneurysm repair (PEVAR) with use of the Perclose Proglide device, in the first period after introduction in our center in 2014. We retrospectively identified all patients that underwent PEVAR or endograft extension with percutaneous approach in our center in the urgent and elective setting. Included were all procedures performed between the introduction of the technique in January 2014 and February 2016 when PEVAR had become the predominant technique in our center. Exclusion progressed from expected difficulty of the procedure as estimated by the operator to total calcification of the ventral wall of the CFA towards the end of the study period. Surgical and clinical reports were used to analyze patient characteristics, procedural success, and short-term outcome after 30 days. Follow-up imaging was used to assess mid-term access site complications at 1 and 2 years postoperatively. A univariate regression analysis was conducted to determine significant predictors of access-related complications with the Perlcose Proglide system. Of all 78 patients (mean age 74, SD: 7 years, 70 men), 68 (87.2%) underwent PEVAR and 10 (12.8%) underwent endograft extension procedures with percutaneous approach. Sixty-seven (85.9%) patients underwent an elective procedure and 11 (14.1%) patients underwent urgent PEVAR. The total number of vessels that was percutaneously accessed was 142. Direct technical success of the procedure as analyzed per vessel was 98.6% (140/142), with two cases of conversion to the femoral cut-down approach. A total of 274 Perclose Proglide devices were placed. Device failure of the Perclose device occurred in 5.8% (16/274) and was reason for conversion to cut-down procedure in one case. Mean duration of the procedure and median time of hospitalization were 100 (SD: 34) min and 2 (IQR 1, 3) days, respectively. Event-free survival per vessel after 30 days was 91.0%, with two minor access-related complication. Fifty-five individual patients (105 vessels) were eligible for inclusion in the 1-year follow-up analysis. Of these patients, 19 (34 vessels) could be included in the 2-year follow-up analysis. No additional access site complications occurred at mid-term follow-up. No significant predictors of device failure were found. The percutaneous approach to EVAR appears to be a safe and effective option with high success rate and low complication rate in a real-world setting. Based on our findings, we conclude that the technique can safely be introduced in a vascular center.

Inadequate Health Literacy in Patients with Arterial Vascular Disease.

OBJECTIVE: The aim was to identify the prevalence of inadequate health literacy in patients with arterial vascular disease. This was a cross sectional study. METHODS: Patients with arterial vascular disease visiting the outpatient clinic between January 5, 2015 and December 28, 2016, were randomly included and screened for inadequate health literacy with the Newest Vital Sign-Dutch (NVS-D), a validated health literacy assessment measure. A score of <4 out of six identified individuals with inadequate health literacy. Age, gender, highest education level, and reason for consultation were also registered. Data analysis was performed using Student's t-test or the Mann-Whitney U test and chi-square test. Logistic regression with backward elimination was applied to identify independent predictors. RESULTS: A total of 202 patients were included. The mean NVS-D score was 1.91 (SD ± 1.948, median 1). The prevalence of inadequate health literacy was 76.7%. A significantly higher prevalence of inadequate health literacy was found in patients ≥65 years (p < .001) and patients with a lower education level (p < .001). No significant difference was found between female/male patients (p = .056), nor between participants with peripheral arterial occlusive disease and abdominal aortic aneurysm (p = .116). Age (OR 1.060; 95% CI 1.017-1.104; p = .005) and education level (OR 0.164; 95% CI 0.078-0.346; p < .001) were identified as independent predictors of inadequate health literacy. CONCLUSION: This study shows a prevalence of inadequate health literacy of 76.7% in patients with arterial vascular disease, with a significantly higher prevalence in patients ≥ 65 years and patients with a lower education level. The high prevalence of inadequate health literacy should be considered when information is provided, and suggests the need to further investigate the best methods to convey medical information to this group of vulnerable patients.

Endovenous laser ablation of insufficient perforating veins: Energy is key to success.

OBJECTIVE: To evaluate the feasibility and anatomical success of endovenous laser ablation (EVLA) of incompetent perforating veins (IPV). METHODS: All 135 consecutive patients with IPV treated with ELVA (intention-to-treat) from January 2008 to December 2013 were included. Up to the end of 2011, an 810-nm laserset (14 W) was used, and afterwards, a 1470-nm laserset (6 W) was introduced. Duplex ultrasound was performed at 6 weeks' follow-up to assess anatomical success. RESULTS: Overall anatomical success at 6 weeks' follow-up was 56%. Anatomical success was 63% after treatment with 810 nm and 45% with 1470 nm (p = 0.035). This difference in the success rate seems associated with the significantly higher amount of energy delivered in the 810 nm cohort (560 J) versus 1470 nm (186 J). Regardless of the type of laser, anatomical success was significantly higher after treatment with more than 400 J (66%) compared with 0-200 J (40%, p = 0.009) and 200-400 J (43%, p = 0.029). Complications were limited to two cases of transient paresthesia. CONCLUSIONS: EVLA of IPVs is safe and feasible. The amount of energy is highly important in achieving anatomical success.

Histological characteristics of the abdominal aortic wall in patients with vascular chronic Q fever.

The aim of this study was to describe specific histological findings of the Coxiella burnetii-infected aneurysmal abdominal aortic wall. Tissue samples of the aneurysmal abdominal aortic wall from seven patients with chronic Q fever and 15 patients without evidence of Q fever infection were analysed and compared. Chronic Q fever was diagnosed using serology and tissue PCR analysis. Histological sections were stained using haematoxylin and eosin staining, Elastica van Gieson staining and immunohistochemical staining for macrophages (CD68), T lymphocytes (CD3), T lymphocyte subsets (CD4 and CD8) and B lymphocytes (CD20). Samples were scored by one pathologist, blinded for Q fever status, using a standard score form. Seven tissue samples from patients with chronic Q fever and 15 tissue samples from patients without Q fever were collected. Four of seven chronic Q fever samples showed a necrotizing granulomatous response of the vascular wall, which was characterized by necrotic core of the arteriosclerotic plaque (P = 0.005) and a presence of high numbers of macrophages in the adventitia (P = 0.007) distributed in typical palisading formation (P = 0.005) and surrounded by the presence of high numbers of T lymphocytes located diffusely in media and adventitia. Necrotizing granulomas are a histological finding in the C. burnetii-infected aneurysmal abdominal aortic wall. Chronic Q fever should be included in the list of infectious diseases with necrotizing granulomatous response, such as tuberculosis, cat scratch disease and syphilis.

Long-term results of Talent endografts for endovascular abdominal aortic aneurysm repair.

BACKGROUND: Since the introduction of endovascular aneurysm repair (EVAR), long-term follow-up studies reporting single-device results are scarce. In this study, we focus on EVAR repair with the Talent stent graft (Medtronic, Santa Rosa, Calif). METHODS: Between July 2000 and December 2007, 365 patients underwent elective EVAR with a Talent device. Patient data were gathered prospectively and evaluated retrospectively. By American Society of Anesthesiologists category, 74% were categories III and IV. Postoperative computed tomography (CT) scanning was performed before discharge, at 3, 12 months, and yearly thereafter. Data are presented according to reporting standards for EVAR. RESULTS: The mean proximal aortic neck diameter was 27 mm (range, 16-36 mm), with a neck length <15 mm in 31% (data available for 193 patients). Deployment of endografts was successful in 361 of 365 patients (99%). Initially, conversion to laparotomy was necessary in four patients. Primary technical success determined by results from computed tomography (CT) scans before discharge was achieved in 333 patients (91%). Proximal type I endoleaks were present in 28 patients (8%) during follow-up, and 14 of these patients needed additional treatment for type I endoleak. The 30-day mortality for the whole Talent group was 1.1% (4 of 365). Follow-up to 84 months is reported for 24 patients. During follow-up, 122 (33%) patients died; in nine, death was abdominal aortic aneurysm (AAA)-related (including 30-day mortality). Kaplan-Meier estimates revealed primary clinical success rates of 98% at 1 year, 93% at 2 years, 88% at 3 years, 79% at 4 years, 64% at 5 years, 51% at 6 years, and 48% at 7 years. Secondary interventions were performed in 73 of 365 patients (20%). Ten conversions for failed endografts were performed. Life-table yearly risk for AAA-related reintervention was 6%, yearly risk for conversion to open repair was 1.1%, yearly risk for total mortality was 8.9%, and yearly risk for AAA-related mortality was 0.8%. CONCLUSION: Initially, technical success of endovascular aneurysm repair (EVAR) using the Talent endograft is high, with acceptable yearly risk for AAA-related mortality and conversion. However, a substantial amount of mainly endovascular reinterventions is necessary during long-term follow-up to achieve these results.

Risk factors for surgical-site infection following common femoral artery endarterectomy.

Surgical-site infection is a major complication following endarterectomy of the common femoral artery. The aim of this single-center study was to determine risk factors for surgical-site infection after endarterectomy of the common femoral artery and especially the possible association between patch type (venous, bovine, or prosthetic) and the occurrence of groin infection. Retrospectively 140 patients who underwent an endarterectomy of the common femoral artery between 2003 and 2006 were reviewed. About 20 patients (14%) suffered from a surgical-site infection (12 superficial and 8 deep, of which 2 with involvement of the patch). All infections occurred within 30 days postoperatively. There was no statistically significant difference between type of patch and surgical-site infection. However, using multivariate analysis, previous arterial surgery in the groin (P = .013) and a wound drain left postoperatively (P = .016) were independent variables for the development of a surgical-site infection after endarterectomy of the common femoral artery.

Low levels of Nogo-B in human carotid atherosclerotic plaques are associated with an atheromatous phenotype, restenosis, and stenosis severity.

OBJECTIVE: Reticulon-4/Nogo (Nogo-B) protects mouse arteries from lumen loss by reducing smooth muscle cell (SMC) migration and intimal thickening. Our goal was to determine plaque and circulating levels of Nogo-B in atherosclerotic and control subjects. Therefore, we studied the relationships between local Nogo-B, plaque characteristics, and clinical data in patients undergoing carotid endarterectomy. METHODS AND RESULTS: Western blot analysis showed that endarterectomy specimens from the femoral (n=19) and carotid arteries (n=145) contained significantly less Nogo-B than nonatherosclerotic mammary arteries (n=8; P<0.003) and aortas (n=15; P=0.03). Immunohistochemistry revealed that in atherosclerotic lesions, Nogo-B was expressed by macrophage/foam cells, SMC rich, and neo-vascularized areas. Atheromatous plaques (>40% fat content) showed a significant reduction in Nogo-B expression (P=0.002). Nogo-B expression levels were significantly lower in patients with more than 90% of carotid stenosis (P=0.04) or restenotic lesions after prior carotid intervention (duplex; P=0.01). In contrast, plasmatic levels of Nogo-B (soluble Nogo-B) did not differ between atherosclerotic subjects (n=68) and risk-factor matched controls (n=63; P=0.5). CONCLUSION: Our findings suggest that local reduction of Nogo-B in atherosclerotic tissue might contribute to plaque formation and/or instability triggering luminal narrowing. In contrast, plasma Nogo-B levels are not associated with clinically manifested atherosclerotic disease.

Gender-associated differences in plaque phenotype of patients undergoing carotid endarterectomy.

BACKGROUND: Carotid endarterectomy to prevent a stroke is less beneficial for women compared with men. This benefit is lower in asymptomatic women compared with asymptomatic men or symptomatic patients. A possible explanation for this gender-associated difference in outcome could be found in the atherosclerotic carotid plaque phenotype. We hypothesize that women, especially asymptomatic women, have more stable plaques than men, resulting in a decreased benefit of surgical plaque removal. METHODS: Carotid endarterectomy specimens of 450 consecutive patients (135 women, 315 men) were studied. The culprit lesions were semi-quantitatively analyzed for the presence of macrophages, smooth muscle cells, collagen, calcifications, and luminal thrombus. Plaques were categorized in three phenotypes according to overall presentation and the amount of fat. Protein was isolated from the plaques for determination of interleukin-6 (IL-6) and IL-8 concentrations and matrix metalloproteinase-8 (MMP-8) and MMP-9 activities. RESULTS: Atheromatous plaques (>40% fat) were less frequently observed in women than in men (22% vs 40%; P < .001). In addition, plaques obtained from women more frequently revealed low macrophage staining (11% vs 18%; P = .05) and strong smooth muscle cell staining (38% vs 24%; P = .001). Compared with men, women had a lower plaque concentration of IL-8 (P = .001) and lower MMP-8 activity (P = .01). The observed differences were most pronounced in asymptomatic women, who showed the most stable plaques, with an atheromatous plaque in only 9% of cases compared with 39% in asymptomatic men (P = .02). In addition, a large proportion of plaques obtained from asymptomatic women showed high smooth muscle cell content (53% vs 30%; P = .03) and high collagen content (55% vs 24%; P = .003). All relations between gender and plaque characteristics, except for MMP-8, remained intact in a multivariate analysis, including clinical presentation and other cardiovascular risk factors. CONCLUSION: Carotid artery plaques obtained from women have a more stable, less inflammatory phenotype compared with men, independent of clinical presentation and cardiovascular risk profile. Asymptomatic women demonstrate the highest prevalence of stable plaques. These findings could explain why women benefit less from carotid endarterectomy compared with men.

Statin treatment is not associated with consistent alterations in inflammatory status of carotid atherosclerotic plaques: a retrospective study in 378 patients undergoing carotid endarterectomy.

BACKGROUND AND PURPOSE: Anti-inflammatory qualities are held partially responsible for the reduction of cardiovascular events after statin treatment. We examined the phenotype of carotid atherosclerotic plaques harvested during carotid endarterectomy in relation to the previous use of different statins prescribed in clinical practice. METHODS: Three hundred and seventy-eight patients were included. Atherosclerotic plaques were harvested, immunohistochemically stained and semiquantitively examined for the presence of macrophages (CD68), smooth muscle cells, collagen and fat. Adjacent atherosclerotic plaques were used to study protease activity and interleukin levels. Patients' demographics were recorded and blood samples were stored. RESULTS: Serum cholesterol, low-density lipoprotein, apolipoprotein B, and C-reactive protein levels were lower in patients treated with statins compared with patients without statin treatment. Atheromatous plaques were less prevalent in patients receiving statins compared with patients without statin therapy (29% versus 42%, P=0.04). An increase of CD68 positive cells was observed in patients receiving statins compared with nonstatin treatment (P=0.05). This effect was specifically related to atorvastatin treatment. In patients treated with atorvastatin, the increased amount of CD68 positive cells were not associated with increased protease activity. In contrast, a dose-dependent decrease in protease activity was shown in the atorvastatin group. Interleukin 6 expression was lower in plaques obtained from patients treated with statins (P=0.04). CONCLUSIONS: Statin use may exert pleiotropic effects on plaque phenotype. However, not the presence of macrophages but activation with subsequent protease and cytokine release may be attenuated by statin use.

Closure of the arteriotomy after carotid endarterectomy: patch type is related to intraoperative microemboli and restenosis rate.

OBJECTIVE: Patch closure after carotid endarterectomy (CEA) improves clinical outcome compared with primary closure. Whether there are differences in outcome between various patch materials is still not clear. The objective of this retrospective study was to investigate whether a relationship exists between the patch type and the number of microemboli as registered during CEA by transcranial Doppler imaging, the clinical outcome (transient ischemic attack and cerebrovascular accident), and the occurrence of restenosis. METHODS: We included 319 patients who underwent CEA. Intraoperative microembolus registration was performed in 205 procedures. Microembolization was recorded during four different periods: dissection, shunting, clamp release, and wound closure. The decision to perform primary closure or to use a patch for the closure of the arteriotomy was made by the surgeon, and Dacron patches were used when venous material was insufficient. Cerebral events were recorded within the first month after CEA, and duplex scanning was performed at 3 months (n = 319) and 1 year (n = 166) after CEA. A diameter reduction of more than 70% was defined as restenosis. RESULTS: Primary, venous, and Dacron patch closures were performed in 83 (26.0%), 171 (53.6%), and 65 (20.4%) patients, respectively. Primary closure was significantly related to sex (Dacron patch, 35 men and 30 women; venous patch, 108 men and 63 women; primary closure, 72 men and 11 women; P < .001). The occurrence of microemboli during wound closure was also related to sex (women, 2.5 +/- 0.6; men, 1.0 +/- 0.2; P = .01). Additionally, during clamp release, Dacron patches were associated with significantly more microemboli than venous patches (11.1 +/- 3.4 vs 4.0 +/- 0.9; P < .01), and this difference was also noted during wound closure (3.1 +/- 0.9 vs 1.4 +/- 0.4; P < .05). Transient ischemic attacks and minor strokes after CEA occurred in 5 (2.4%) of 205 and 6 (2.9%) of 205 procedures, respectively, and the degree of microembolization during dissection was related to adverse cerebral events (P = .003). In contrast, the type of closure was not related to immediate clinical adverse events. However, primary closure and Dacron patches were associated with an increase in the restenosis rate compared with venous patches: after 400 days, the restenosis rate for Primary closure was 11%, Dacron patch 16%, and venous patch 7% (P = .05; Kaplan-Meier estimates). CONCLUSIONS: Microemboli are more prevalent during clamp releases and wound closure when Dacron patches are used. Additionally, the observed differences in embolization noted by patch type were mainly evident in women. However, the use of Dacron patches was not related to immediate ischemic cerebral events but was associated with a higher restenosis rate compared with venous patch closure. This suggests that venous patch closure may be preferred for CEA.

Athero-express: differential atherosclerotic plaque expression of mRNA and protein in relation to cardiovascular events and patient characteristics. Rationale and design.

In clinical practice, biological markers are not available to routinely assess the progression of atherosclerotic disease or the development of restenosis following endarterectomy or catheter based interventions. Endarterectomy procedures provide an opportunity to study mechanisms of restenosis and progression of atherosclerotic disease since atherosclerotic tissue is obtained. Athero-Express is an ongoing prospective study, initiated in 2002, with the objective to investigate the etiological value of plaque characteristics for long term outcome. Patients are included who undergo an endarterectomy of the carotid artery. At baseline blood is withdrawn, patients fill in an extensive questionnaire and diagnostic examinations are performed. Atherosclerotic plaques are freshly harvested, immunohistochemically stained and examined for the presence of macrophages, smooth muscle cells, collagen and fat. Parts of the atherosclerotic plaques are freshly frozen to study protease activity and protein and RNA expressions. Patients undergo a duplex follow up to assess procedural restenosis (primary endpoint) at 3 months, 1 year and 2 years. Secondary endpoints encompass major adverse cardiovascular events. In the future, the creation of this biobank with atherosclerotic specimen will allow the design of cross-sectional and follow up studies with the objective to investigate the expression of newly discovered genes and proteins and their interaction with patients and plaque characteristics in the progression of atherosclerotic disease. Objective is to include 1000-1200 patients in 5 years. In January 2004, 289 patients had been included. It is expected that 250 patients will be included yearly.