Global Vascular Guidelines on the Management of Chronic Limb-Threatening Ischemia.

GUIDELINE SUMMARY: Chronic limb-threatening ischemia (CLTI) is associated with mortality, amputation, and impaired quality of life. These Global Vascular Guidelines (GVG) are focused on definition, evaluation, and management of CLTI with the goals of improving evidence-based care and highlighting critical research needs. The term CLTI is preferred over critical limb ischemia, as the latter implies threshold values of impaired perfusion rather than a continuum. CLTI is a clinical syndrome defined by the presence of peripheral artery disease (PAD) in combination with rest pain, gangrene, or a lower limb ulceration >2 weeks duration. Venous, traumatic, embolic, and nonatherosclerotic etiologies are excluded. All patients with suspected CLTI should be referred urgently to a vascular specialist. Accurately staging the severity of limb threat is fundamental, and the Society for Vascular Surgery Threatened Limb Classification system, based on grading of Wounds, Ischemia, and foot Infection (WIfI) is endorsed. Objective hemodynamic testing, including toe pressures as the preferred measure, is required to assess CLTI. Evidence-based revascularization (EBR) hinges on three independent axes: Patient risk, Limb severity, and ANatomic complexity (PLAN). Average-risk and high-risk patients are defined by estimated procedural and 2-year all-cause mortality. The GVG proposes a new Global Anatomic Staging System (GLASS), which involves defining a preferred target artery path (TAP) and then estimating limb-based patency (LBP), resulting in three stages of complexity for intervention. The optimal revascularization strategy is also influenced by the availability of autogenous vein for open bypass surgery. Recommendations for EBR are based on best available data, pending level 1 evidence from ongoing trials. Vein bypass may be preferred for average-risk patients with advanced limb threat and high complexity disease, while those with less complex anatomy, intermediate severity limb threat, or high patient risk may be favored for endovascular intervention. All patients with CLTI should be afforded best medical therapy including the use of antithrombotic, lipid-lowering, antihypertensive, and glycemic control agents, as well as counseling on smoking cessation, diet, exercise, and preventive foot care. Following EBR, long-term limb surveillance is advised. The effectiveness of nonrevascularization therapies (eg, spinal stimulation, pneumatic compression, prostanoids, and hyperbaric oxygen) has not been established. Regenerative medicine approaches (eg, cell, gene therapies) for CLTI should be restricted to rigorously conducted randomizsed clinical trials. The GVG promotes standardization of study designs and end points for clinical trials in CLTI. The importance of multidisciplinary teams and centers of excellence for amputation prevention is stressed as a key health system initiative.

Do thrombotic events during endovascular interventions lead to poorer outcomes in patients with severe limb ischemia?

INTRODUCTION: Intra-procedural acute thrombosis (IPAT) is a complication of endovascular procedures. We aim to identify risk factors for IPAT and compare the outcomes of patients with or without IPAT. METHODS: Paired T test and χ (2) test were used to identify risk factors and short-term outcomes. Kaplan-Meier survival analysis was used for mid-term outcomes. RESULTS: A total of 228 procedures were performed with 21 IPAT events (9.21%). The odds ratio of Indian patients developing IPAT was 2.8x (95% CI 1.1-7.6). Patients with in-stent occlusion or prior IPAT were 5.6x (95% CI 1.3-24.2) and 5.6x (95% CI 1.3-24.4) more likely to develop an IPAT event. Patients without IPAT had significantly more improvement in mean runoff score (-1.15 ± 1.31, p < 0.01). The odds of patients with IPAT requiring subsequent endovascular intervention and arterial bypass surgery were 4.2x (95% CI 1.6-10.7) and 7.1x (95% CI 1.9-27.0). There was no significant Kaplan-Meier estimated overall survival or amputation-free survival difference between patients with or without IPAT event. CONCLUSION: Indian ethnicity, in-stent occlusion and previous IPAT were associated with higher risk of IPAT. Even after successful endovascular salvage, patients with IPATs were more likely to require secondary revascularization procedure. Patients with IPATs had no decrease in overall survival or amputation-free survival.

Cilostazol for intermittent claudication.

BACKGROUND: Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication, characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age-matched controls, people with intermittent claudication have a three- to six-fold increase in cardiovascular mortality. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise programme. Antiplatelet treatment is beneficial in patients with intermittent claudication for the reduction of vascular events but has not previously been shown to influence claudication distance. This is an update of a review first published in 2007. OBJECTIVES: To determine the effect of cilostazol (an antiplatelet treatment) on improving initial and absolute claudication distances, and in reducing mortality and vascular events in patients with stable intermittent claudication. SEARCH METHODS: For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9). SELECTION CRITERIA: Double-blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We performed the meta-analysis as a fixed-effect model with weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous data, and odds ratios (ORs) with 95% CIs for dichotomous data. MAIN RESULTS: We included fifteen double-blind, RCTs comparing cilostazol with placebo, or medications currently known to increase walking distance e.g. pentoxifylline. There were a total of 3718 randomised participants with treatment durations ranging from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Comparisons included cilostazol twice daily, with dosages of 50 mg, 100 mg and 150 mg compared with placebo, and cilostazol 100 mg, twice daily, compared with pentoxifylline 400 mg, three times daily. The methodological quality of the trials was generally low, with the majority being at an unclear risk for selection bias, performance bias, detection bias and other bias. Attrition bias was generally low, but reporting bias was high or unclear in the majority of the studies. For eight studies data were compatible for comparison by meta-analysis, but data for seven studies were too heterogenous to be pooled. For the studies included in the meta-analysis, for initial claudication distance (ICD - the distance walked on a treadmill before the onset of calf pain) there was an improvement in the cilostazol group for the 100 mg and 50 mg twice daily, compared with placebo (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; P < 0.00001) and WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; P = 0.0002), respectively. ICD was improved in the cilostazol group for the comparison of cilostazol 150 mg versus placebo and cilostazol 100 mg versus pentoxifylline, but only single studies were used for these analyses. Absolute claudication distance (ACD - the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg and 50 mg twice daily, compared with placebo (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; P = 0.0007) and WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; P = 0.0004), respectively. As with ICD, ACD was increased in participants taking cilostazol 150 mg versus placebo, but with only one study an association cannot be clearly determined. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise CI (WMD 13.42 metres (95% CI -43.51 to 70.35 metres; P = 0.64). Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; P < 0.00001). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI.There was no association between treatment type and all-cause mortality for any of the treatment comparisons, but there were very few events, and therefore larger, adequately powered studies will be needed to assess if there is a relationship. Only one study evaluated individual cardiovascular events, and from this study there is no clear evidence of a difference between any of the treatment groups and risk of myocardial infarction or stroke. We evaluated adverse side effects, and in general cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations. We only reported quality of life measures descriptively as there was insufficient statistical detail within the studies to combine the results, although there was a possible indication in improvement of quality of life in the cilostazol treatment groups. AUTHORS' CONCLUSIONS: Cilostazol has been shown to be of benefit in improving walking distance in people with intermittent claudication secondary to PAD. Although there is an increase in adverse side effects, they are generally mild and treatable. There is currently insufficient data on whether taking cilostazol results in a reduction of all-cause mortality and cardiovascular events or an improvement in quality of life. Future research into the effect of cilostazol on intermittent claudication should carefully consider comparability, sample size and homogeneity when designing a study.

Comparative outcomes of primary autogenous fistulas in elderly, multiethnic Asian hemodialysis patients.

BACKGROUND: The number of elderly (≥65 years) end-stage renal disease (ESRD) patients on hemodialysis is rapidly increasing. Vascular access outcomes remain contradictory and understudied across different elderly populations. We hypothesized age might influence primary autogenous fistula use and outcomes in a predominantly diabetic multiethnic Asian ESRD population. METHODS: Demographic and clinical factors affecting fistula patency and maturation were retrospectively compared among patients with incident ESRD aged <65 and ≥65 years at a single center. Fistula patency was estimated by Kaplan-Meier curves with log-rank test comparison. RESULTS: We analyzed 280 primary fistulas (59% radiocephalic, 33% brachiocephalic, and 8% brachiobasilic) in this cohort consisting of 31.8% aged ≥65 years, 50% Chinese, 39% Malay, 42% women, and 70% diabetic. One- and 2-year primary and secondary patency in patients aged <65 vs ≥65 years were comparable: 41.3% vs 36.7% and 28.7% vs 24.4% (P = .547) and 57.7% vs 56.8% and 47.1% vs 47.2% (P = .990). On multivariate analysis, only non-Chinese, dialysis initiation with tunneled catheters, and surgical/endovascular interventions affected fistula survival hazard ratios (HR): 0.622 (95% confidence interval [CI], 0.43-1.00), 0.549 (95% CI, 0.297-0.841), and 2.503 (95% CI, 1.695-3.697), respectively. Nonmaturation and intervention rates were also similar at 56.7% vs 61.8% and 34% vs 32.2% at 3 and 6 months and 0.31 vs 0.36 per access year, respectively (P > .05). Females and tunneled catheters were the only risk factors for nonmaturation (HR, 1.568; 95% CI, 1.148-1.608, and HR, 1.623; 95% CI, 1.400-1.881, respectively). CONCLUSIONS: A primary fistula strategy in incident elderly ESRD is feasible and does not result in inferior outcomes. Age should therefore not be a determinant for primary fistula creation.

Antiplatelet agents for intermittent claudication.

BACKGROUND: Peripheral arterial disease (PAD) is common and is a marker of systemic atherosclerosis. Patients with symptoms of intermittent claudication (IC) are at increased risk of cardiovascular events (myocardial infarction (MI) and stroke) and of both cardiovascular and all cause mortality. OBJECTIVES: To determine the effectiveness of antiplatelet agents in reducing mortality (all cause and cardiovascular) and cardiovascular events in patients with intermittent claudication. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases group searched their Specialised Register (last searched April 2011) and CENTRAL (2011, Issue 2) for publications on antiplatelet agents and IC. In addition reference lists of relevant articles were also searched. SELECTION CRITERIA: Double-blind randomised controlled trials comparing oral antiplatelet agents versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication were included. Patients with asymptomatic PAD (stage I Fontaine), stage III and IV Fontaine PAD, and those undergoing or awaiting endovascular or surgical intervention were excluded. DATA COLLECTION AND ANALYSIS: Data on methodological quality, participants, interventions and outcomes including all cause mortality, cardiovascular mortality, cardiovascular events, adverse events, pain free walking distance, need for revascularisation, limb amputation and ankle brachial pressure indices were collected. For each outcome, the pooled risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) was calculated. MAIN RESULTS: A total of 12 studies with a combined total of 12,168 patients were included in this review. Antiplatelet agents reduced all cause (RR 0.76, 95% CI 0.60 to 0.98) and cardiovascular mortality (RR 0.54, 95% CI 0.32 to 0.93) in patients with IC compared with placebo. A reduction in total cardiovascular events was not statistically significant (RR 0.80, 95% CI 0.63 to 1.01). Data from two trials (which tested clopidogrel and picotamide respectively against aspirin) showed a significantly lower risk of all cause mortality (RR 0.73, 95% CI 0.58 to 0.93) and cardiovascular events (RR 0.81, 95% CI 0.67 to 0.98) with antiplatelets other than aspirin compared with aspirin. Antiplatelet therapy was associated with a higher risk of adverse events, including gastrointestinal symptoms (dyspepsia) (RR 2.11, 95% CI 1.23 to 3.61) and adverse events leading to cessation of therapy (RR 2.05, 95% CI 1.53 to 2.75) compared with placebo; data on major bleeding (RR 1.73, 95% CI 0.51, 5.83) and on adverse events in trials of aspirin versus alternative antiplatelet were limited. Risk of limb deterioration leading to revascularisation was significantly reduced by antiplatelet treatment compared with placebo (RR 0.65, 95% CI 0.43 to 0.97). AUTHORS' CONCLUSIONS: Antiplatelet agents have a beneficial effect in reducing all cause mortality and fatal cardiovascular events in patients with IC. Treatment with antiplatelet agents in this patient group however is associated with an increase in adverse effects, including GI symptoms, and healthcare professionals and patients need to be aware of the potential harm as well as the benefit of therapy; more data are required on the effect of antiplatelets on major bleeding. Evidence on the effectiveness of aspirin versus either placebo or an alternative antiplatelet agent is lacking. Evidence for thienopyridine antiplatelet agents was particularly compelling and there is an urgent need for multicentre trials to compare the effects of aspirin against thienopyridines.

Asia-Pacific Consensus Statement on the Management of Peripheral Artery Disease: A Report from the Asian Pacific Society of Atherosclerosis and Vascular Disease Asia-Pacific Peripheral Artery Disease Consensus Statement Project Committee.

BACKGROUND: Peripheral artery disease (PAD) is the most underdiagnosed, underestimated and undertreated of the atherosclerotic vascular diseases despite its poor prognosis. There may be racial or contextual differences in the Asia-Pacific region as to epidemiology, availability of diagnostic and therapeutic modalities, and even patient treatment response. The Asian Pacific Society of Atherosclerosis and Vascular Diseases (APSAVD) thus coordinated the development of an Asia-Pacific Consensus Statement (APCS) on the Management of PAD. OBJECTIVES: The APSAVD aimed to accomplish the following: 1) determine the applicability of the 2016 AHA/ACC guidelines on the Management of Patients with Lower Extremity Peripheral Artery Disease to the Asia-Pacific region; 2) review Asia-Pacific literature; and 3) increase the awareness of PAD. METHODOLOGY: A Steering Committee was organized to oversee development of the APCS, appoint a Technical Working Group (TWG) and Consensus Panel (CP). The TWG appraised the relevance of the 2016 AHA/ACC PAD Guideline and proposed recommendations which were reviewed by the CP using a modified Delphi technique. RESULTS: A total of 91 recommendations were generated covering history and physical examination, diagnosis, and treatment of PAD-3 new recommendations, 31 adaptations and 57 adopted statements. This Asia-Pacific Consensus Statement on the Management of PAD constitutes the first for the Asia-Pacific Region. It is intended for use by health practitioners involved in preventing, diagnosing and treating patients with PAD and ultimately the patients and their families themselves.

Limb salvage in patients with peripheral arterial disease managed by endovascular first approach.

This study aims to review the outcome of patients with peripheral arterial disease (PAD) managed with endovascular first approach for revascularization in a tertiary referral center. Revascularization procedures were performed in 202 patients with 229 symptomatic limbs. Angiogram was performed in all patients except those contraindicated for contrast agent. Angioplasty revascularization was carried out on the same setting whenever feasible based on the angiogram findings. Bypass surgery was performed in patients with arterial condition not feasible for endovascular intervention or in those with unsatisfactory revascularization after endovascular treatment. Endovascular intervention was successfully performed in 198 limbs. Bypass surgery was required in 31 patients. Another 16 patients required a bypass after endovascular intervention due to unsatisfactory wound healing. The Kaplan-Meier estimated survival and amputation-free survival were 80% and 75.5% at 1 year and 73% and 57.6% at 2 years, respectively. Satisfactory limb salvage rate can be achieved in patients with PAD managed with endovascular first approach.

Outcomes of initial hemodialysis access surgery in an Asian population.

PURPOSE: Access-related morbidity contributes substantially to the costs of hemodialysis. The aim of this study was to examine the outcomes of initial hemodialysis access surgery at a single center in Singapore and to analyze factors which might influence survival of the surgically-created access. METHODS: Patients undergoing their first hemodialysis access operations between January 2003 and December 2007 were retrospectively identified. Primary and assisted primary patency rates were determined by the Kaplan-Meier method. Data on age, sex, diabetic status, and prior tunneled central venous catheter (CVC) use were analyzed against the outcome of arteriovenous fistulas (AVF). RESULTS: During the study period, 410 primary upper limb access operations were performed: 297 forearm AVF (72.4%), 91 upper arm AVF (22.2%), and 22 arteriovenous grafts (AVG; 5.4%). Men comprised 55.4%, 271 (66.1%) had diabetes, and 316 patients (77.1%) came to surgery with pre-existing CVC. Sixty-two percent of forearm AVF and 67% of arm AVF were used successfully. Age, sex, diabetes, and prior use of a CVC did not significantly affect the ability to use an AVF. Only in the female diabetic subgroup was an earlier loss of primary assisted patency of AVF recorded. CONCLUSIONS: In our Asian population, we have demonstrated AVF patency rates equivalent to those of international centers. We now face the challenge of achieving a higher rate of pre-emptive AVF placement with a subsequent reduction in CVC use.

Central vein stenosis in an Asian hemodialysis population.

OBJECTIVE AND BACKGROUND: Central vein stenosis occurs commonly after instrumentation of the major thoracic veins. We aimed to investigate factors that contributed to this condition in an Asian hemodialysis population, and the results of intervention. PATIENTS AND METHODS: Hemodialysis patients diagnosed with central vein stenosis between January 2003 and December 2008, were identified from the records of the National University Hospital, Singapore. Eligible controls had a minimum of 2 years of hemodialysis via an arteriovenous fistula and/or central venous catheter, without clinical or radiological evidence of central vein stenosis. RESULTS: Central vein stenosis was diagnosed in 108 patients. The most common presenting features were arm swelling (32%) and failed hemodialysis catheter insertion (28%). The median frequency of permanent hemodialysis catheter insertion in those who subsequently developed venous stenosis (1.44 per patient per year) was 4 times that of controls (0.36 per patient per year; p<0.001). Ischemic heart disease (p = 0.03) and in certain patients, arteriovenous fistula surgery were associated with the development of central vein stenosis; whereas line sepsis, diabetes, and hypertension were not. Central vein angioplasty was attempted in 53 patients; the primary patency was 52% at 1 year. CONCLUSION: Central vein stenosis is associated with a higher frequency of hemodialysis catheter insertion and access surgery. Efforts to decrease permanent hemodialysis catheter use should reduce the incidence of central vein stenosis.

Does the introduction of a third examiner and global marking improve the generalisability of the surgical long case?

INTRODUCTION: Planning a high-stake clinical examination requires the evaluation of several psychometric and logistical variables. The authors conducted generalisability and decision studies to answer the following research questions in the context of the surgical long case: (1) Does the addition of a third examiner have any added benefit, vis-à-vis reliability, to the examination? (2) Is global marking more reliable than an itemised marking template? (3) What would be the impact on reliability if there was a reduction in the number of examinees that each panel of examiners is required to assess? METHODS: A third examiner and global marking were introduced. Separate generalisability and decision studies were carried out for both the two- and three-examiner models as well as for itemised and global scores. RESULTS: The introduction of a third examiner resulted in a modest gain of reliability by 0.05-0.07. Gain in reliability was higher when each candidate was allowed to undertake a higher number of clinical cases. Both the global and itemised scores provided equivalent reliability (generalisability coefficient 0.74-0.89). CONCLUSION: Our results showed that only a modest improvement in reliability of the surgical long case is achieved through the introduction of an additional examiner. Although the reliability of global scoring and the itemised marking template was comparable, the latter may provide opportunities for individualised feedback to examinees.

Late relapse of non-typhoidal salmonella vascular graft infection after 5 years.

Salmonella bacteremia can be complicated by mycotic aneurysm with the potential for a catastrophic presentation. Treatment involves prompt surgery with debridement, extraanatomic bypass, and prolonged antibiotic therapy. Any relapse tends to occur within the 1(st) year after surgery. We describe a case of Salmonella enteritidis mycotic aneurysm in a 56-year-old man 5 years after the initial presentation, emphasizing the importance of aggressive initial therapy and long-term surveillance.

Outcomes of endovascular intervention for salvage of failing hemodialysis access.

OBJECTIVE: To investigate the effectiveness of endovascular balloon angioplasty to preserve the patency of failing hemodialysis arteriovenous fistulas (AVF) and prosthetic arteriovenous grafts (AVG). METHODS: Patients on hemodialysis who received endovascular intervention for access problems were retrospectively analyzed. Fistulography was performed on patients who were suspected to have access stenosis and balloon angioplasty performed in the same setting if a stenosis of ≥50% is detected. Patients were followed up for post-operative complications and access restenosis or failure. RESULTS: 42 hemodialysis patients with 44 access sites (29 AVFs, 15 AVGs) required endovascular balloon angioplasty. There were no perioperative complications. Technical success rate was 100%. Median time from initial access creation to first balloon angioplasty was 13 months (2-146 months) for AVFs and 8 months (2-71 months) for AVGs. 19 of 44 patients subsequently developed restenosis. Median time for restenosis or access failure was 11 months (1-18 months) for AVFs and 5 months (1-10 months) for AVGs. Kaplan-Meier analysis for access patency after endovascular intervention showed 72% patency at 6 months and 32% at 12 months. CONCLUSIONS: Endovascular balloon angioplasty is effective in restoring patency of failing hemodialysis accesses. Recurrence is common, and repeat interventions are required.