The Global Limb Anatomic Staging System (GLASS) for CLTI: Improving Inter-Observer Agreement.

OBJECTIVE: The 2020 Global Vascular Guidelines aim at improving decision making in Chronic Limb-Threatening Ischemia (CLTI) by providing a framework for evidence-based revascularization. Herein, the Global Limb Anatomic Staging System (GLASS) serves to estimate the chance of success and patency of arterial pathway revascularization based on the extent and distribution of the atherosclerotic lesions. We report the preliminary feasibility results and observer variability of the GLASS. GLASS is a part of the new global guideline and posed as a promising additional tool for EBR strategies to predict the success of lower extremity arterial revascularization. This study reports on the consistency of GLASS scoring to maximize inter-observer agreement and facilitate its application. METHODS: GLASS separately scores the femoropopliteal (FP) and infrapopliteal (IP) segment based on stenosis severity, lesion length and the extent of calcification within the target artery pathway (TAP). In our stepwise approach, we used two angiographic datasets. Each following step was based on the lessons learned from the previous step. The primary outcome was inter-observer agreement measured as Cohen's Kappa, scored by two (step 1 + 2) and four (step 3) blinded and experienced observers, respectively. Steps 1 (n = 139) and 2 (n = 50) were executed within a dataset of a Dutch interventional RCT in CLTI. Step 3 (n = 100) was performed in randomly selected all-comer CLTI patients from two vascular centers in the United States. RESULTS: In step 1, kappa values were 0.346 (FP) and 0.180 (IP). In step 2, applied in the same dataset, the use of other experienced observers and a provided TAP, resulted in similar low kappa values 0.406 (FP) and 0.089 (IP). Subsequently, in step 3, the formation of an altered stepwise approach using component scoring, such as separate scoring of calcification and adding a ruler to the images resulted in kappa values increasing to 0.796 (FP) and 0.730 (IP). CONCLUSION: This retrospective GLASS validation study revealed low inter-observer agreement for unconditioned scoring. A stepwise component scoring provides acceptable agreement and a solid base for further prospective validation studies to investigate how GLASS relates to treatment outcomes.

Prognostic value of the Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) classification in patients with no-option chronic limb-threatening ischemia.

OBJECTIVE: The Wound, Ischemia, and foot Infection (WIfI) classification was developed to assess amputation risk and hence to aid in clinical decision-making in patients with chronic limb-threatening ischemia (CLTI). WIfI has been validated in multiple CLTI cohorts worldwide. In this study, we examined the relationship between WIfI stage and clinical outcomes in a well-defined subpopulation of CLTI patients considered not eligible for conventional revascularization. The aim of this study was to assess the prognostic value of the WIfI classification for clinical outcomes in a "no-option" CLTI population. METHODS: The Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-arterial Supplementation (JUVENTAS) trial was a single-center, double-blinded, randomized placebo-controlled trial studying the effects of autologous bone marrow mononuclear cells in no-option CLTI patients (N = 160). We conducted a retrospective analysis incorporating baseline and follow-up data from the JUVENTAS trial. All wounds were photographed and described at the start and end of the trial to allow WIfI staging. Two independent researchers retrospectively classified all limbs according to the WIfI scheme, which was then related to prospectively collected trial data. Outcomes including wound healing, clinical improvement, minor and major amputation rate, amputation-free survival, and mortality were assessed using Kaplan-Meier analyses. RESULTS: Of the 160 patients, 150 could be included in this study. Most patients had been classified as Rutherford stage 4 (34%) and stage 5 (61%), with corresponding WIfI stage 2 (33%), stage 3 (21%), or stage 4 (35%). Diabetes, impaired renal function, and ankle-brachial index were independently associated with WIfI stage. On univariate analysis, WIfI stage was strongly associated with wound healing (P = .001), improvement of Rutherford stage (P = .009), amputation rate (P < .001), and long-term mortality (median follow-up, 21.1 months; P = .025). Of note, WIfI stage 2 patients had a worse 6-month major amputation rate compared with stage 3. Of the seven amputated stage 2 patients, six were in WIfI category W0-I3-fI0 and scored a maximum grade 3 on ischemia. Reclassification of ischemic rest pain (W0-I3-fI0) to stage 3 improved and reordered the discrimination of outcomes by WIfI stage in this cohort. CONCLUSIONS: This is the first study to demonstrate that WIfI classification is associated with important clinical outcomes in a no-option CLTI population. Our data suggest that limb prognosis is poor in patients with classic ischemic rest pain, without wounds or infection (W0-I3-fI0), when they lack revascularization options. Further studies are needed to determine whether reassignment of this population from WIfI stage 2 to WIfI stage 3 may be appropriate to reflect amputation risk in the absence of successful revascularization for patients suffering from ischemic rest pain in general.

Atherosclerotic plaque characteristics are not associated with future cardiovascular events in patients undergoing iliofemoral endarterectomy.

BACKGROUND: Plaque characteristics such as intraplaque hemorrhage (IPH) have been associated with secondary cardiovascular events (CVE) in patients undergoing carotid endarterectomy. In addition, carotid plaques containing macrophage infiltration or a large lipid core size were associated with less restenosis. It is currently unknown whether iliofemoral plaque histopathologic characteristics are predictive for secondary CVE in patients with peripheral arterial disease undergoing iliofemoral endarterectomy. The aim of this study was to examine the association between iliofemoral atherosclerotic plaque characteristics and secondary CVE in patients undergoing iliofemoral endarterectomy. METHODS: There were 497 patients with iliofemoral atherosclerotic disease who underwent primary endarterectomy of the iliac or femoral artery from 2002 to 2013 included. All specimen were uptaken in the Athero Express biobank and 7 histologic plaque characteristics were analyzed: calcification, collagen, fat content, IPH, macrophages, smooth muscle cells, and vessel density. The composite CVE consisted of myocardial infarction, cerebrovascular accident, peripheral (re-)interventions, and cardiovascular death. Multivariate Cox regression models were used to examine the association between plaque and the composite end point during a follow-up period of 3 years. RESULTS: Of the 497 patients, 225 (46.4%) experienced a composite CVE within 3 years after the initial surgery. Calcified plaques were univariably associated with composite CVE (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.00-1.73; P = .049). After correction for confounders, multivariable analyses showed no association between calcified plaques and composite CVE (HR, 1.13; 95% CI, 0.85-1.50; P = .413). IPH was not predictive of secondary CVE (HR, 1.02; 95% CI, 0.79-1.33; P = .867). CONCLUSIONS: In this cohort of patients with peripheral arterial disease undergoing iliofemoral endarterectomy, investigated atherosclerotic plaque characteristics were not independently associated with secondary CVE during follow-up.

Patients with diabetes differ in atherosclerotic plaque characteristics and have worse clinical outcome after iliofemoral endarterectomy compared with patients without diabetes.

OBJECTIVE: Diabetes mellitus (DM) is associated with peripheral arterial disease (PAD) and leads to worse clinical outcome compared with patients without DM. The objective of this study was to determine the impact of DM on iliofemoral artery plaque characteristics and to examine secondary clinical outcomes in patients with DM and PAD undergoing surgical revascularization. METHODS: We analyzed 198 patients with and 453 patients without DM from the Athero-Express biobank, a prospective ongoing biobank study, who underwent endarterectomy of the femoral or iliac artery between 2002 and 2013. Seven histologic plaque characteristics (calcification, collagen, lipid core, intraplaque hemorrhage, macrophages, microvessels, and smooth muscle cells) and secondary clinical outcome were compared. Composite outcome consisted of any of the following secondary manifestations of cardiovascular disease: stroke, myocardial infarction, cardiovascular death, or peripheral intervention. In addition, target vessel revascularization (TVR) was examined. The follow-up period was standardized at 3 years after the procedure. RESULTS: Patients with DM were more likely to have calcified plaques compared with patients without DM (odds ratio, 2.11; 95% confidence interval, 1.43-3.12; P < .01). No other plaque characteristic differed significantly between the two groups. In total, 112 (57.1%) patients with DM and 198 (45.1%) patients without DM reached a composite end point during follow-up, of whom 21 (10.7%) and 27 (6.2%) died of cardiovascular causes, respectively. DM was an independent predictor of composite cardiovascular events (hazard ratio, 1.36; 95% confidence interval, 1.020-1.801; P = .01) during follow-up. No difference in the incidence of TVR was observed between patients with and without DM (31.5% and 30%, respectively; difference in survival time, P = .86) or in longer duration of DM with composite event-free survival (difference in survival time, P = .57). CONCLUSIONS: Patients with DM who undergo surgical revascularization for PAD with the use of thromboendarterectomy or remote endarterectomy have a more calcified atherosclerotic plaque and an increased incidence in composite cardiovascular events but no increase in TVR.

Time-dependent differences in femoral artery plaque characteristics of peripheral arterial disease patients.

BACKGROUND AND AIMS: Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis with an increasing incidence worldwide. The disease is still associated with high morbidity and mortality risks. Previous research in carotid arteries indicates that atherosclerotic plaque characteristics have stabilized over time in patients considered for surgery. It is currently unknown whether this time-dependent stabilization occurs in ilio-femoral arteries as well. Our objective was to analyze whether local ilio-femoral atherosclerotic plaque characteristics have changed over time. METHODS: 497 patients within the Athero-Express biobank who underwent primary endarterectomy of the iliac or femoral artery between 2002 and 2013 were analyzed. We investigated six histological plaque characteristics: calcification, collagen, fat content, intraplaque haemorrhage, macrophages and smooth muscle cells. RESULTS: Over the course of 10 years, we observed a lower percentage of all plaque characteristics that are considered indicators of a vulnerable plaque, such as: plaques with a large lipid core from 37.9% to 14.9% and plaques with intraplaque haemorrhage from 69.0% to 34.8% when the two-year cohorts 2003-2004 and 2011-2012 were compared, respectively. Multivariable analyses showed that time-dependent changes occurred independently of changing procedural and patient characteristics. CONCLUSIONS: In this cohort of peripheral arterial disease patients undergoing primary endarterectomy, we observed a time dependent shift of plaque characteristics towards a less lipid rich lesion with less intraplaque haemorrhage. These findings indicate research in cardiovascular disease would benefit from contemporary patient characteristics and plaque specimens to optimize translational potential.

Current status and future perspectives of bioresorbable stents in peripheral arterial disease.

BACKGROUND: Endovascular treatment of peripheral arterial disease (PAD) still yields unsatisfactory patency rates. Recent new developments include the use of bioresorbable stents. The objective of this study was to provide an overview of currently available data on the use of bioresorbable stents in lower limb PAD and to summarize the needs for future research focus. METHODS: A systematic search in the databases of MEDLINE, Embase, and the Cochrane Library was performed. Studies using predefined inclusion and exclusion criteria were included and critically appraised by two independent reviewers. Inclusion criteria were (1) original data on (2) bioresorbable stents in (3) lower limb arteries including the iliac tract. Primary end points were safety and feasibility of bioresorbable stents, including 30-day adverse events. Secondary end points included radial force, bioresorption process, long-term primary and secondary patency, and clinical outcomes, such as amputation rate, Rutherford category, and ankle-brachial index improvement. RESULTS: Seven published studies with a total of 316 patients were included, and five conference abstracts including 272 patients were assessed. Median follow-up time was 12 months. Overall technical success rate was 99% (range, 95.0%-100%). The 30-day adverse event rates were reported in 5.0% of patients (range, 0%-13.3%); these included one death, two major amputations, and seven reinterventions. Mean primary patency rate was 61.6% in the femoral arteries (range, 32.1%-80.0%) after 6 to 12 months compared with 50.3% in below-the-knee lesions (range, 31.8%-92.9%). Secondary patency rates were 91.5% (range, 84%-97.1%) and 72.1% (range, 62.9%-100%), respectively. The 1-year amputation rate was 3.0% in the whole group (range, 0%-12.4%). CONCLUSIONS: Experience with the use of bioresorbable stents in PAD is still limited and is investigated only in small studies. The use of bioresorbable stents in PAD appears to be feasible and safe. With current published results, we are unable to fully answer all of the questions about the future use of bioresorbable stents in PAD, and use should be limited to study-related cases in PAD.