Editor's Choice - Management of Lower Extremity Venous Outflow Obstruction: Results of an International Delphi Consensus.

OBJECTIVE: The endovascular treatment of venous obstruction has expanded significantly in recent years. Best practices for optimal patient outcomes are not well established and the evidence base is poor. The purpose of this study was to obtain consensus on management criteria for patients with lower extremity venous outflow obstruction. METHODS: The study was conducted as a two round Delphi consensus. Statements addressed imaging, symptoms and other baseline measures, differential diagnosis, treatment algorithm, indications for stenting, inflow and outflow assessment, successful procedural outcomes, post-procedure therapies and stent surveillance, and clinical success factors. Statements were prepared by six expert physicians (round 1, 40 statements) and an expanded panel of 24 physicians (round 2, 80 statements) and sent to a pre-identified group of venous experts who met qualifying criteria. A 9 point Likert scale was used and consensus was defined as ≥ 70% of respondents rating a statement between 7 and 9 (agreement) or between 1 and 3 (disagreement). Round 1 results were used to guide rewording and splitting compound statements for greater clarity in round 2. RESULTS: In round 1, 75 of 110 (68%) experts responded, and 91 of 121 (75%) experts responded in round 2. Round 1 achieved consensus in 32/40 (80%) statements. Consensus was not reached in the treatment algorithm section. Round 2 achieved consensus in 50/80 (62.5%). Statements reaching consensus were imaging (2/3, 66%), symptoms and other baseline measures (12/24, 50%), differential diagnosis (2/8, 25%), treatment algorithm (10/17, 59%), indications for stenting (10/10, 100%), inflow and outflow assessment (2/2, 100%), procedural outcomes (2/2, 100%), post-procedure therapies and stent surveillance, (5/7, 71%), and clinical success factors (5/7, 71%). CONCLUSION: This study demonstrated that considerable consensus was achieved between venous experts on the optimal management of lower extremity venous outflow obstruction. There were multiple domains where consensus is lacking, highlighting important areas for further investigation and research.

Metabolic Profiling Reveals Changes in Serum Predictive of Venous Ulcer Healing.

OBJECTIVE: The aim of this study was to identify potential biomarkers predictive of healing or failure to heal in a population with venous leg ulceration. SUMMARY BACKGROUND DATA: Venous leg ulceration presents important physical, psychological, social and financial burdens. Compression therapy is the main treatment, but it can be painful and time-consuming, with significant recurrence rates. The identification of a reliable biochemical signature with the ability to identify nonhealing ulcers has important translational applications for disease prognostication, personalized health care and the development of novel therapies. METHODS: Twenty-eight patients were assessed at baseline and at 20 weeks. Untargeted metabolic profiling was performed on urine, serum, and ulcer fluid, using mass spectrometry and nuclear magnetic resonance spectroscopy. RESULTS: A differential metabolic phenotype was identified in healing (n = 15) compared to nonhealing (n = 13) venous leg ulcer patients. Analysis of the assigned metabolites found ceramide and carnitine metabolism to be relevant pathways. In this pilot study, only serum biofluids could differentiate between healing and nonhealing patients. The ratio of carnitine to ceramide was able to differentiate between healing phenotypes with 100% sensitivity, 79% specificity, and 91% accuracy. CONCLUSIONS: This study reports a metabolic signature predictive of healing in venous leg ulceration and presents potential translational applications for disease prognostication and development of targeted therapies.

Design of a treatment satisfaction measure for patients undergoing varicose vein treatment: Venous Treatment Satisfaction Questionnaire (VenousTSQ).

BACKGROUND: Established condition-specific patient-reported outcome measures for varicose veins are limited to the measurement of health status and function. A treatment satisfaction measure is needed to understand patient satisfaction with different treatment options. The aim of this study was to design a Venous Treatment Satisfaction Questionnaire (VenousTSQ) that would be ready for large-scale data collection and psychometric evaluation. METHODS: Relevant items were selected from the -TSQ Item Library and new items were designed where necessary. A draft VenousTSQ was prepared using the existing AneurysmTSQ as a template. Fifteen interviews were conducted from 4 days to 16 months after the procedure. The interviews were designed to elicit important sources of satisfaction or dissatisfaction before completion of draft questionnaires. The VenousTSQ drafts were modified between sets of interviews until no further changes were required. RESULTS: The final VenousTSQ consists of two questionnaires: VenousTSQ early (VenousTSQe) and VenousTSQ status (VenousTSQs). Items that need be asked only once are in the VenousTSQe, whereas those that can usefully be asked more than once are in the VenousTSQs. Of the 16 unique items forming the VenousTSQ, 12 were from the -TSQ Item Library. Only 1 of these 12 required significant modification. CONCLUSIONS: The VenousTSQ represents a condition-specific psychological outcome measure for varicose veins, enabling patient satisfaction or dissatisfaction with such treatments to be measured. Large-scale data collection is under way to establish optimal scoring, quantitative validity, and reliability of the VenousTSQ.

Neuromuscular Electrical Stimulation for Intermittent Claudication (NESIC): multicentre, randomized controlled trial.

METHODS: This was an open, multicentre, randomized controlled trial. Patients with intermittent claudication attending vascular surgery outpatient clinics were randomized (1:1) to receive either neuromuscular electrical stimulation (NMES) or not in addition to local standard care available at study centres (best medical therapy alone or plus supervised exercise therapy (SET)). The objective of this trial was to investigate the clinical efficacy of an NMES device in addition to local standard care in improving walking distances in patients with claudication. The primary outcome was change in absolute walking distance, measured by a standardized treadmill test at 3 months. Secondary outcomes included intermittent claudication (IC) distance, adherence, quality of life, and haemodynamic changes. RESULTS: Of 200 participants randomized, 160 were included in the primary analysis (intention to treat, Tobit regression model). The square root of absolute walking distance was analysed (due to a right-skewed distribution) and, although adjunctive NMES improved it at 3 months, no statistically significant effect was observed. SET as local standard care seemed to improve distance compared to best medical therapy at 3 months (3.29 units; 95 per cent c.i., 1.77 to 4.82; P < 0.001). Adjunctive NMES improved distance in mild claudication (2.88 units; 95 per cent c.i., 0.51 to 5.25; P = 0.02) compared to local standard care at 3 months. No serious adverse events relating to the device were reported. CONCLUSION: Supervised exercise therapy is effective and NMES may provide further benefit in mild IC.This trial was supported by a grant from the Efficacy and Mechanism Evaluation Program, a Medical Research Council and National Institute for Health and Care Research partnership. Trial registration: ISRCTN18242823.

Patients with intermittent claudication experience pain in their legs during walking or exercise which ends with rest. This severely impairs physical activity and quality of life. Treatment for such patients typically involves best medical therapy, which includes exercise advice. This study aimed to determine whether a neuromuscular electrical stimulation device improved the walking distance of patients with intermittent claudication compared to local standard care available (which may include supervised exercise therapy) in a trial. Supervised exercise improved walking distances but there was no difference in those that received a device in this patient group.

A Randomized Trial of Early Endovenous Ablation in Venous Ulceration.

BACKGROUND: Venous disease is the most common cause of leg ulceration. Although compression therapy improves venous ulcer healing, it does not treat the underlying causes of venous hypertension. Treatment of superficial venous reflux has been shown to reduce the rate of ulcer recurrence, but the effect of early endovenous ablation of superficial venous reflux on ulcer healing remains unclear. METHODS: In a trial conducted at 20 centers in the United Kingdom, we randomly assigned 450 patients with venous leg ulcers to receive compression therapy and undergo early endovenous ablation of superficial venous reflux within 2 weeks after randomization (early-intervention group) or to receive compression therapy alone, with consideration of endovenous ablation deferred until after the ulcer was healed or until 6 months after randomization if the ulcer was unhealed (deferred-intervention group). The primary outcome was the time to ulcer healing. Secondary outcomes were the rate of ulcer healing at 24 weeks, the rate of ulcer recurrence, the length of time free from ulcers (ulcer-free time) during the first year after randomization, and patient-reported health-related quality of life. RESULTS: Patient and clinical characteristics at baseline were similar in the two treatment groups. The time to ulcer healing was shorter in the early-intervention group than in the deferred-intervention group; more patients had healed ulcers with early intervention (hazard ratio for ulcer healing, 1.38; 95% confidence interval [CI], 1.13 to 1.68; P=0.001). The median time to ulcer healing was 56 days (95% CI, 49 to 66) in the early-intervention group and 82 days (95% CI, 69 to 92) in the deferred-intervention group. The rate of ulcer healing at 24 weeks was 85.6% in the early-intervention group and 76.3% in the deferred-intervention group. The median ulcer-free time during the first year after trial enrollment was 306 days (interquartile range, 240 to 328) in the early-intervention group and 278 days (interquartile range, 175 to 324) in the deferred-intervention group (P=0.002). The most common procedural complications of endovenous ablation were pain and deep-vein thrombosis. CONCLUSIONS: Early endovenous ablation of superficial venous reflux resulted in faster healing of venous leg ulcers and more time free from ulcers than deferred endovenous ablation. (Funded by the National Institute for Health Research Health Technology Assessment Program; EVRA Current Controlled Trials number, ISRCTN02335796 .).

A multicenter randomized controlled study to evaluate whether neuromuscular electrical stimulation improves the absolute walking distance in patients with intermittent claudication compared with best available treatment.

OBJECTIVE: To assess the clinical efficacy of a neuromuscular electrical stimulation (NMES) device to improve the absolute walking distance in patients with intermittent claudication as an adjunct to the local standard care available at the study sites compared with local standard care alone. METHODS: This open, multicenter, randomized controlled trial included eight participating centers in England. Sites are equally distributed between those that provide supervised exercise therapy programs and those that do not. Patients with intermittent claudication meeting the eligibility criteria and providing consent will be randomized, depending on the center type, to either NMES and locally available standard care or standard care alone. The primary end point is change in absolute walking distance at 3 months (the end of the intervention period) by treadmill testing. Secondary outcomes include quality of life, compliance with the interventions, economic evaluation of the NMES device, and lower limb hemodynamic measures to further the understanding of underlying mechanisms. Recruitment commenced in March 2018 and will continue for a total of 15 months. The Neuromuscular Electrical Stimulation Improves the Absolute Walking Distance in Patients with Intermittent Claudication trial is funded by the UK Efficacy and Mechanism Evaluation Programme, Medical Research Council, and National Institute for Health Research partnership.

The Abdominal Aortic Aneurysm Statistically Corrected Operative Risk Evaluation (AAA SCORE) for predicting mortality after open and endovascular interventions.

BACKGROUND: Accurate adjustment of surgical outcome data for risk is vital in an era of surgeon-level reporting. Current risk prediction models for abdominal aortic aneurysm (AAA) repair are suboptimal. We aimed to develop a reliable risk model for in-hospital mortality after intervention for AAA, using rigorous contemporary statistical techniques to handle missing data. METHODS: Using data collected during a 15-month period in the United Kingdom National Vascular Database, we applied multiple imputation methodology together with stepwise model selection to generate preoperative and perioperative models of in-hospital mortality after AAA repair, using two thirds of the available data. Model performance was then assessed on the remaining third of the data by receiver operating characteristic curve analysis and compared with existing risk prediction models. Model calibration was assessed by Hosmer-Lemeshow analysis. RESULTS: A total of 8088 AAA repair operations were recorded in the National Vascular Database during the study period, of which 5870 (72.6%) were elective procedures. Both preoperative and perioperative models showed excellent discrimination, with areas under the receiver operating characteristic curve of .89 and .92, respectively. This was significantly better than any of the existing models (area under the receiver operating characteristic curve for best comparator model, .84 and .88; P < .001 and P = .001, respectively). Discrimination remained excellent when only elective procedures were considered. There was no evidence of miscalibration by Hosmer-Lemeshow analysis. CONCLUSIONS: We have developed accurate models to assess risk of in-hospital mortality after AAA repair. These models were carefully developed with rigorous statistical methodology and significantly outperform existing methods for both elective cases and overall AAA mortality. These models will be invaluable for both preoperative patient counseling and accurate risk adjustment of published outcome data.

Independence and mobility after infrainguinal lower limb bypass surgery for critical limb ischemia.

BACKGROUND: Critical limb ischemia (CLI) is a common condition associated with high levels of morbidity and mortality. Most work to date has focused on surgeon-oriented outcomes such as patency, but there is increasing interest in patient-oriented outcomes such as mobility and independence. OBJECTIVE: This study was conducted to determine the effect of infrainguinal lower limb bypass surgery (LLBS) on postoperative mobility in a United Kingdom tertiary vascular surgery unit and to investigate causes and consequences of poor postoperative mobility. METHODS: We collected data on all patients undergoing LLBS for CLI at our institution during a 3-year period and analyzed potential factors that correlated with poor postoperative mobility. RESULTS: During the study period, 93 index LLBS procedures were performed for patients with CLI. Median length of stay was 11 days (interquartile range, 11 days). The 12-month rates of graft patency, major amputation, and mortality were 75%, 9%, and 6%, respectively. Rates of dependence increased fourfold during the first postoperative year, from 5% preoperatively to 21% at 12 months. Predictors of poor postoperative mobility were female sex (P = .04) and poor postoperative mobility (P < .001), initially and at the 12-month follow-up. Patients with poor postoperative mobility had significantly prolonged hospital length of stay (15 vs 8 days; P < .001). CONCLUSIONS: Patients undergoing LLBS for CLI suffer significantly impaired postoperative mobility, and this is associated with prolonged hospital stay, irrespective of successful revascularization. Further work is needed to better predict patients who will benefit from revascularization and in whom a nonoperative strategy is optimal.

European and US guidelines on acute DVT management.

Acute deep venous thrombosis (DVT) is a common health problem, affecting millions of patients in Europe and the United States annually. Europe and US national clinical practice guidelines are formulated by evaluation of the available scientific evidence, with expert opinion to create pragmatic guidance for the optimal patient management, representing the best available knowledge at the time of publication, and providing the best evidence-based recommendations for vascular patient care and venous pathologies. We here focus on the novel recommendations proposed by European and US guidelines for acute DVT, denoting main differences between the two panels. This review gives vascular surgeons the opportunity to identify the key points of the two largest Vascular Committees guidelines, in order to use them and offer their best individualized treatment approach to the specific patient's anatomy, lesion, and history.

Evaluating pharmacological THRomboprophylaxis in Individuals undergoing superficial endoVEnous treatment across NHS and private clinics in the UK: a multi-centre, assessor-blind, randomised controlled trial-THRIVE trial.

INTRODUCTION: Endovenous therapy is the first choice management for symptomatic varicose veins in NICE guidelines, with 56-70 000 procedures performed annually in the UK. Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a known complication of endovenous therapy, occurring at a rate of up to 3.4%. Despite 73% of UK practitioners administering pharmacological thromboprophylaxis to reduce VTE, no high-quality evidence supporting this practice exists. Pharmacological thromboprophylaxis may have clinical and cost benefit in preventing VTE; however, further evidence is needed. This study aims to establish whether when endovenous therapy is undertaken: a single dose or course of pharmacological thromboprophylaxis alters the risk of VTE; pharmacological thromboprophylaxis is associated with an increased rate of bleeding events; pharmacological prophylaxis is cost effective. METHODS AND ANALYSIS: A multi-centre, assessor-blind, randomised controlled trial (RCT) will recruit 6660 participants from 40 NHS and private sites across the UK. Participants will be randomised to intervention (single dose or extended course of pharmacological thromboprophylaxis plus compression) or control (compression alone). Participants will undergo a lower limb venous duplex ultrasound scan at 21-28 days post-procedure to identify asymptomatic DVT. The duplex scan will be conducted locally by blinded assessors. Participants will be contacted remotely for follow-up at 7 days and 90 days post-procedure. The primary outcome is imaging-confirmed lower limb DVT with or without symptoms or PE with symptoms within 90 days of treatment. The main analysis will be according to the intention-to-treat principle and will compare the rates of VTE at 90 days, using a repeated measures analysis of variance, adjusting for any pre-specified strongly prognostic baseline covariates using a mixed effects logistic regression. ETHICS AND DISSEMINATION: Ethical approval was granted by Brent Research Ethics Committee (22/LO/0261). Results will be disseminated in a peer-reviewed journal and presented at national and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN18501431.

Scoring systems for the post-thrombotic syndrome.

OBJECTIVE: To assess each of the scoring systems used to diagnose and classify post-thrombotic syndrome, a common chronic complication of deep vein thrombosis. The design of the study was a systematic review of the literature pertaining to post-thrombotic syndrome. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines by a search of PubMed (1948 to September 2011) using the search terms "post-thrombotic syndrome," "postthrombotic syndrome," "post-phlebitic syndrome," and "postphlebitic syndrome." A manual reference list search was also carried out to identify further studies that would be appropriate for inclusion. The various scoring systems in use were identified and assessed against a list of criteria to determine their validity for use. For outcome measures, each scoring system was assessed for specific criteria, including interobserver reliability, association with ambulatory venous pressures, ability to assess severity of post-thrombotic syndrome, ability to assess change in condition over time, and association with patient-reported symptom severity. RESULTS: The Villalta, Ginsberg, Brandjes, Widmer, CEAP, and Venous Clinical Severity Score systems all were assessed for the stated outcome measures. From their use in the literature, only the Villalta score was able to fulfill all the criteria described. The main criticism of the Villalta score in the literature appears to be its use of subjective measures. To that end, we propose that use of a venous disease-specific quality-of-life questionnaire in combination with the Villalta score may help standardize the subjective criteria. CONCLUSIONS: The Villalta score, combined with a venous disease-specific quality-of-life questionnaire, should be considered the "gold standard" for the diagnosis and classification of post-thrombotic syndrome.

Examining the benefit of graduated compression stockings in the prevention of hospital-associated venous thromboembolism in low-risk surgical patients: a multicentre cluster randomised controlled trial (PETS trial).

INTRODUCTION: Hospital-acquired thrombosis (HAT) is defined as any venous thromboembolism (VTE)-related event during a hospital admission or occurring up to 90 days post discharge, and is associated with significant morbidity, mortality and healthcare-associated costs. Although surgery is an established risk factor for VTE, operations with a short hospital stay (<48 hours) and that permit early ambulation are associated with a low risk of VTE. Many patients undergoing short-stay surgical procedures and who are at low risk of VTE are treated with graduated compression stockings (GCS). However, evidence for the use of GCS in VTE prevention for this cohort is poor. METHODS AND ANALYSIS: A multicentre, cluster randomised controlled trial which aims to determine whether GCS are superior in comparison to no GCS in the prevention of VTE for surgical patients undergoing short-stay procedures assessed to be at low risk of VTE. A total of 50 sites (21 472 participants) will be randomised to either intervention (GCS) or control (no GCS). Adult participants (18-59 years) who undergo short-stay surgical procedures and are assessed as low risk of VTE will be included in the study. Participants will provide consent to be contacted for follow-up at 7-days and 90-days postsurgical procedure. The primary outcome is the rate of symptomatic VTE, that is, deep vein thrombosis or pulmonary embolism during admission or within 90 days. Secondary outcomes include healthcare costs and changes in quality of life. The main analysis will be according to the intention-to-treat principle and will compare the rates of VTE at 90 days, measured at an individual level, using hierarchical (multilevel) logistic regression. ETHICS AND DISSEMINATION: Ethical approval was granted by the Camden and Kings Cross Research Ethics Committee (22/LO/0390). Findings will be published in a peer-reviewed journal and presented at national and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN13908683.

Salvage antegrade visceral revascularization and antegrade aortic stenting for type I and III endoleaks after fenestrated juxtarenal aneurysm repair.

A 73-year-old man developed type I and III endoleaks from a fractured right renal stent with downward migration of a fenestrated endograft, 6 years after endovascular repair of a juxtarenal aneurysm. Endovascular treatment attempts were unsuccessful. He underwent aortic debranching and antegrade visceral artery revascularization via a left thoracolaparotomy incision and an extraperitoneal approach to the visceral aorta. An antegrade aortic stent covered the endoleak, with technical and clinical success at 9 months. Failure of complex endografts presents particular problems, potentially not amenable to totally endovascular repair. Continued surveillance is mandated as late, asymptomatic sac expansion can occur.

Reducing errors in combined open/endovascular arterial procedures: influence of a structured mental rehearsal before the endovascular phase.

PURPOSE: To assess the incidence of errors before and after implementation of a structured mental rehearsal prior to the endovascular phase of combined open/endovascular arterial procedures. METHODS: Over 6 weeks, 15 combined open/endovascular procedures (7 abdominal aorta and 8 thoracic aorta) lasting 58 hours were evaluated by a trained observer. In a blinded fashion, 2 individuals scrutinized event logs for errors, which were categorized by type, by potential to cause patient harm (danger), and by potential to disrupt the procedure (delay). After 9 procedures, a focus group-devised structured mental rehearsal was implemented prior to the endovascular phase for 6 combined procedures. Error patterns were compared before and after implementation. Data are expressed as median (range). RESULTS: The error rate during the endovascular phase of the combined procedures was higher than the non-endovascular phase [7.64/hour (1.71-9.6) vs. 3.75/hour (1.71-5.54), respectively; p = 0.05]. Error rates during the endovascular phase were lower after the intervention compared to before [2.5/hour (1.4-6.0) vs. 7.6/hour (1.7-9.6), respectively; p = 0.05]. During the endovascular phase, danger and delay scores were also lower after the intervention [1.2/error (1.0-2.0) and 1.3/error (1.0-2.3), respectively] compared to before [1.75/error (1.4-2.5) and 2.0/error (1.3-2.5), respectively] (p = 0.036 and p = 0.036 for danger and delay, respectively). CONCLUSION: A structured mental rehearsal before critical stages of procedures may reduce the rate and severity of intraoperative error.