The Impact of Intravascular Ultrasound on Femoropopliteal Artery Endovascular Interventions: A Randomized Controlled Trial.

OBJECTIVES: The aim of this study was to investigate whether the addition of intravascular ultrasound (IVUS) guidance during femoropopliteal artery interventions reduced the rate of binary restenosis within 12 months compared with angiographic guidance alone. BACKGROUND: IVUS is more accurate than angiography for assessment of vessel size and disease severity. Low-level studies suggest that the use of IVUS in femoropopliteal endovascular interventions improves outcomes, but currently, no level 1 evidence exists. METHODS: This was a prospective single-center trial of 150 patients undergoing femoropopliteal endovascular intervention, randomized (1:1) to guidance by angiography or angiography and IVUS. The primary outcome measure was freedom from binary restenosis, on duplex ultrasound, within 12 months. Secondary outcomes included clinically driven target lesion revascularization, disagreements in imaging findings between modalities, and changes in treatment caused by IVUS. RESULTS: Freedom from binary restenosis at 12 months was significantly higher in the IVUS group (72.4% vs 55.4%; P = 0.008). There was no significant difference between groups for clinically directed target lesion revascularization (84.2% and 82.4%; P = 0.776). Mean vessel diameter was significantly larger with IVUS (5.60 mm vs 5.10 mm; P < 0.001). A change in treatment occurred caused by IVUS in 79% of cases. Binary restenosis was lower in the IVUS group for cases treated with drug-coated balloons (9.1% vs 37.5%; P = 0.001). CONCLUSIONS: The use of IVUS resulted in a significant reduction in the rate of restenosis after endovascular intervention. This is the first randomized controlled trial to demonstrate that IVUS improves outcomes in femoropopliteal interventions. This benefit may primarily relate to cases treated with drug-coated balloons. (Does the use of intravascular ultrasound improve outcomes of endovascular interventional procedures for peripheral vascular disease of the superficial femoral artery or popliteal artery?; ACTRN12614000006640).

The effect of supervised exercise therapy for intermittent claudication on lower limb lean mass.

OBJECTIVE: Supervised exercise is currently recommended for the first-line treatment of intermittent claudication based on improvement in walking capacity. However, the promotion of skeletal muscle atrophy by repetitive ischemia-reperfusion caused by treadmill-based programs remains a concern. Because preservation of skeletal muscle mass (SMM) and lean mass (LM) is integral to functional capacity and longevity, this study measured the effect of standard treadmill-based supervised exercise on SMM and regional lower limb LM in patients with intermittent claudication. METHODS: Patients with calf claudication caused by infrainguinal peripheral artery disease underwent whole-body dual-energy X-ray absorptiometry scanning before and after completion of a 12-week supervised treadmill exercise program. Total body SMM and lower limb LM were measured according to anatomical regions of the lower limb (thigh vs calf) and side of symptoms. Walking performance was assessed using pain-free walking distance and 6-minute walking distance tests. RESULTS: Thirty-six patients with calf claudication completed exercise training and dual-energy X-ray absorptiometry scanning, allowing analysis of 55 symptomatic and 17 asymptomatic lower limbs. No difference in total body SMM (P = .41) or LM of symptomatic (P = .53) or asymptomatic calves (P = .59) was detected after the program. In contrast, a significant decrease in LM was observed in symptomatic (P = .04) and asymptomatic thighs (P = .005). Pain-free walking distance (P = .001) and the 6-minute walking distance both improved significantly (P = .004) but were not associated with changes in LM. CONCLUSIONS: Twelve weeks of standard treadmill-training for intermittent calf claudication did not result in loss of calf LM; however, a significant decrease in bilateral thigh LM was observed, even in patients with unilateral symptoms. Further research on optimum exercise modalities and end points are required to determine the pathophysiology and effects of these changes on function and survival.

A Comparison of Measures of Endothelial Function in Patients with Peripheral Arterial Disease and Age and Gender Matched Controls.

This study compared flow-mediated dilatation (FMD), peripheral artery tonometry (PAT), and serum nitric oxide (NO) measures of endothelial function in patients with peripheral artery disease (PAD) against age/gender matched controls. 25 patients (mean age: 72.4 years, M : F 18 : 7) with established PAD and an age/gender matched group of 25 healthy controls (mean age: 72.4 years, M : F 18 : 7) were studied. Endothelial function was measured using the % FMD, reactive hyperemia index (RHI) using PAT and serum NO (µmol). Difference for each method between PAD and control patients and correlation between the methods were investigated. FMD and RHI were lower in patients with PAD (median FMD for PAD = 2.16% versus control = 3.77%, p = 0.034 and median RHI in PAD = 1.64 versus control = 1.92, p = 0.005). NO levels were not significantly different between the groups (PAD median = 7.70 µmol, control median = 13.05 µmol, p = 0.662). These results were obtained in elderly patients and cannot be extrapolated to younger individuals. FMD and PAT both demonstrated a lower hyperaemic response in patients with PAD; however, FMD results in PAD patients were unequivocally reduced whereas half the PAD patients had RHI values above the established threshold for endothelial dysfunction. This suggests that FMD is a more appropriate method for the measurement of NO-mediated endothelial function.

Do Medications Commonly Prescribed to Patients with Peripheral Arterial Disease Have an Effect on Nutritional Status? A Review of the Literature.

BACKGROUND: Polypharmacy is common among patients with peripheral arterial disease (PAD) with a combination of medications used for risk-factor modification and medical management of the disease itself. Interaction between commonly prescribed medications and nutritional status has not previously been well described. This review aims to critically appraise evidence exploring associations between medications commonly prescribed to patients with PAD and nutritional status and provide recommendations for practice. METHODS: A comprehensive literature search was conducted to locate studies relating to nutrient interactions among lipid-lowering, antihypertensive, antiplatelet, and oral hypoglycemic drug classes. Quality of the evidence was rated on the basis of recommendations by the National Health and Medical Research Council. RESULTS: A total of 25 articles were identified as suitable and included in the review. No studies were specific to patients with PAD, and hence findings highlighting risk of ubiquinone (coenzyme Q10 [CoQ10]) depletion with lipid-lowering medications, zinc depletion with antihypertensive medications, and vitamin B12 depletion with oral hypoglycemic medications are extrapolated from heterogeneous groups of patients and healthy adults. The body of evidence ranged in quality from satisfactory to poor. CONCLUSIONS: High-quality research is required to confirm the interactions suggested by the included studies in patients with PAD specifically. It is, however, recommended that patients with PAD that are long-term consumers of the selected medications are monitored for CoQ10, zinc, and vitamin B12 to facilitate early identification of deficiencies and initiation of treatment. Treatment may involve dietary intervention and/or supplementation.

The impact of different supervised exercise regimens on endothelial function in patients with intermittent claudication.

BACKGROUND AND OBJECTIVES: The impact of supervised exercise training on endothelial function in patients with intermittent claudication is unclear. This study assesses the impact of treadmill-based supervised exercise training alone or in combination with resistance training on pain free walking distance, flow-mediated dilatation, reactive hyperaemia index, nitric oxide and asymmetric dimethylarginine. METHODS: Thirty-five patients with intermittent claudication were randomised to 12 weeks of treadmill-only supervised exercise training (Group 1) or a combination of treadmill and lower-limb resistance supervised exercise training (Group 2). Pain free walking distance was assessed by six-minute walk test. Endothelial function was assessed by brachial artery flow-mediated dilatation, reactive hyperaemia index and serum analysis of asymmetric dimethylarginine and nitric oxide. RESULTS: Pain free walking distance improved within Group 1 (160 m to 204 m, p = 0.03) but not Group 2 (181 m to 188 m, p = 0.82), no between group difference. No significant change in flow-mediated dilatation or reactive hyperaemia index in either group. Nitric oxide decreased in Group 1 (15.0 µmol/L to 8.3 µmol/L, p = 0.003) but not Group 2 (11.2 µmol/L to 9.1 µmol/L, p = 0.14), p = 0.07 between groups. Asymmetric dimethylarginine decreased in Group 2 (0.61 µmol/L to 0.56 µmol/L, p = 0.03) but not Group 1 (0.58 µmol/l to 0.58 µmol/L, p = 0.776), no between group difference. CONCLUSION: Supervised exercise training does not improve endothelial function as measured by flow-mediated dilatation, reactive hyperaemia index and nitric oxide bioavailability.

Change in dietary intake of adults with intermittent claudication undergoing a supervised exercise program and compared to matched controls.

BACKGROUND: Presence of numerous diet responsive comorbidities and high atherosclerotic burden among adults with intermittent claudication demands attention is given to diet in an effort to delay progression of peripheral artery disease. The aim of this study was to compare diet of adults with intermittent claudication: (a) against dietary recommendations; (b) following 12 weeks of supervised exercise training; and (c) against non-peripheral artery disease controls. METHODS: Diet was assessed using a food frequency questionnaire pre and post supervised exercise training. Pre-exercise diet was compared against Suggested Dietary Targets and against non-peripheral artery disease controls matched for gender, age and body weight. Pre-exercise diet was also compared against post-exercise diet. RESULTS: Pre-exercise 25/31 participants, 5/31 participants, 16/31 participants and 4/31 participants achieved recommendations for protein, carbohydrate, total fat and saturated fat respectively. Few achieved recommended intakes for fibre (3/31 participants), cholesterol (8/31 participants), folate (11/31 participants), potassium (1/31 participants), sodium (4/31 participants), retinol equivalents (1/31 participants) and vitamin C (3/31 participants). There were no differences observed between participants compared to controls in achievement of recommendations. Post-exercise, marginally more participants were able to achieve targets for cholesterol, sodium and vitamin C but not for any other nutrients. CONCLUSIONS: Despite evidence to support benefits of dietary modification in risk reduction of peripheral artery disease, adults with intermittent claudication continue to consume poor diets. Research is required to determine whether dietary changes can be achieved with greater attention to nutrition counselling and the impact assessed in terms of delayed disease progression and long term health outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01871779.

Neutrophil-lymphocyte ratio as a prognostic marker of outcome in infrapopliteal percutaneous interventions for critical limb ischemia.

BACKGROUND: Endovascular intervention has become a frequently used treatment of critical limb ischemia (CLI) in recent times. The recent Bypass vs Angioplasty in Severe Ischaemia of the Leg (BASIL) trial consensus recommended endovascular treatment as a first-line treatment in patients who have a life expectancy that was limited to <2 years. Despite these recommendations, there still remains limited data available to clinicians when seeking to risk stratify patients who present with CLI. The neutrophil-lymphocyte ratio (NLR) has been suggested to be a marker for predicting mortality and patency. This study aimed to investigate the use of the NLR as a prognostic marker for primary patency and mortality after an infrapopliteal endovascular intervention in patients with CLI. METHODS: All patients who underwent tibial angioplasty for CLI were retrospectively analyzed. Demographics, degrees of stenosis, vessel patency rates, mortality, and comorbidities were recorded. NLRs were calculated from preoperative blood samples. Primary end points were all-cause mortality, primary patency, and amputation-free survival (AFS) within the follow-up period of 12 months. Multivariate Cox proportional hazard models were used to identify independent predictors. Overall survival, AFS, and the probability of a vessel remaining patent were evaluated by standard Kaplan-Meier survival curves and groups compared by the log-rank test. RESULTS: Eighty-three patients were monitored for 12 months. Ninety limbs were identified, with 104 procedural events and 127 vessels undergoing successful angioplasty. The technical success rate was 86%, and patency at 1 year was 19%. Survival at 1 year was 76% and AFS was 61%. Patients with a NLR ≥5.25 had an increased risk of death (hazard ratio, 1.97; 95% confidence interval, 1.08-3.62; P = .03) compared with those with a NLR of <5.25. Furthermore, those with lymphocytes counts of <1.5 × 10(9)/L had higher mortality (hazard ratio, 1.88; 95% confidence interval, 1.02-3.70; P = .045) than those with lymphocyte counts >1.5 × 10(9)/L. CONCLUSIONS: The NLR and absolute lymphocyte counts are potentially valuable prognostic indicators for risk stratification of patient's presenting with CLI undergoing infrapopliteal angioplasty.

A systematic review to evaluate the effectiveness of carnitine supplementation in improving walking performance among individuals with intermittent claudication.

OBJECTIVE: To evaluate the evidence for the use of carnitine supplementation in improving walking performance among individuals with intermittent claudication. DESIGN: Systematic review. METHODS: An electronic search of the literature was performed using MEDLINE (PubMed), Scopus, Cochrane Central Register of Controlled Trials and The Cochrane Library from inception through to November 2012. Search terms included peripheral arterial disease, intermittent claudication and carnitine. Reference lists of review articles and primary studies were also examined. Full reports of published experimental studies including randomized controlled trials and pre-test/post-test trials were selected for inclusion. A quality assessment was undertaken according to the Jadad scale. RESULTS: A total of 40 articles were retrieved, of which 23 did not meet the inclusion criteria. The 17 included articles reported on a total of 18 experimental studies of carnitine supplementation (5 pre-test/post-test; 8 parallel RCT; 5 cross-over RCT) for improving walking performance in adults with intermittent claudication. For pre-test/post-test studies, 300-2000 mg propionyl-L-carnitine (PLC) was administered orally or intravenously for a maximum of 90 days (7-42 participants) with statistically significant improvements of between 74 m and 157 m in pain free walking distance and between 71 m and 135 m in maximal walking distance across 3 out of 5 studies. Similarly, PLC (600 mg-3000 mg) was administered orally in 7 out of 8 parallel RCTs (22-485 participants), the longest duration being 12 months. All but one of the smallest trials demonstrated statistically significant improvements in walking performance between 31 and 54 m greater than placebo for pain free walking distance and between 9 and 86 m greater than placebo for maximal walking distance. A double-blind parallel RCT of cilostazol plus 2000 mg oral L-carnitine or placebo for 180 days (145 participants) did not demonstrate any significant improvement in walking performance. Of 5 cross-over RCTs (8-20 participants), 4 demonstrated significant improvements in walking performance following administration of 300-6000 mg L-carnitine or PLC. Compared to placebo, pain free walking distance and maximal walking distance improved by 23-132 m and 104 m respectively following carnitine intervention. CONCLUSIONS: Most trials demonstrated a small or modest improvement in walking performance with administration of PLC or L-carnitine. These findings were largely independent of level or quality of evidence, while there was some evidence that intravenous administration was more effective than oral administration and those with severe claudication may achieve greater benefits than those with moderate claudication. Routine carnitine supplementation in the form of PLC may therefore be a useful adjunct therapy for management of intermittent claudication. Further research is warranted to determine the optimal form, duration, dose and safety of carnitine supplementation across the spectrum of peripheral arterial disease severity and its effect with concurrent supervised exercise programs and best medical therapy. These studies should be supplemented with cost effectiveness studies to ensure that the return on the investment is acceptable.

Stroke and transient ischaemic attack awareness.

OBJECTIVE: This study examined the knowledge of stroke warning signs and risk factors among the general public, including what they would do if they were to develop such symptoms. DESIGN, SETTING AND PARTICIPANTS: Population study of randomly selected members of the general public in Adelaide, South Australia. A simple survey assessed knowledge of stroke warning signs and gave four options for management. The survey was conducted on three separate occasions: before, immediately after and 3 months after the National Stroke Foundation's National Stroke Week in 2009. MAIN OUTCOME MEASURES: The outcome measures were the public perception of risk factors and warning signs of stroke and what the members of the public would do if presented with a range of warning signs. They were also asked about their knowledge of the Face, Arms, Speech, Time (FAST) test. RESULTS: The three surveys were completed by 251 members of the public. Hypertension and smoking were recognised as risk factors for stroke by 71% and 53% of respondents respectively. Before National Stroke Week, slurred speech was identified by 51% and both slurred speech and upper limb sensory loss was identified by 62% as warning signs to provoke presentation to an emergency department (ED). Amaurosis, upper limb sensory loss, upper limb numbness and upper limb weakness were correctly identified individually as warning signs to attend an ED by fewer than one-third of respondents. There was no significant difference in the survey results following National Stroke Week. CONCLUSIONS: Public awareness of the symptoms of stroke, and what to do about them, is limited. There was little improvement after the national week-long awareness campaign. The lack of public awareness about stroke warning signs must be addressed to reduce mortality and morbidity from stroke.

Vascular reconstruction in lower limb musculoskeletal tumours.

BACKGROUND: Individual experience in the investigative, planning and operative aspects of lower limb musculoskeletal tumours is often small, making comparison between results difficult. The aim of the study was to describe the recent experience of a single tertiary referral unit performing limb salvage surgery, to identify areas of concern that are amenable to intervention and to provide clinicians an understanding of the surgical options. METHODS: Nine patients with peripheral limb musculoskeletal tumours are described. Four patients had a leiomyosarcoma, and one each of osteosarcoma, synovial chondrosarcoma, synovial sarcoma, liposarcoma and recurrent malignant peripheral nerve sheath tumour. RESULTS: Thirty-day mortality was nil. Two patients (one with a leiomyosarcoma and one with an osteosarcoma) died at 6 months follow-up because of pulmonary metastases. One patient with synovial chondrosarcoma developed a local recurrence and underwent an above-knee amputation. Six patients at 18 months follow-up are alive with no evidence of local recurrence and a functional lower limb. CONCLUSION: These cases are a challenge to the clinicians, radiologists and pathologists. Review by a multidisciplinary team can produce successful results with low post-operative morbidity and mortality. Longer follow-up is required to determine the long-term implications.

Endovascular repair of abdominal aortic aneurysm reduces intraoperative cortisol and perioperative morbidity.

BACKGROUND: The release of catabolic stress hormones because of surgical trauma leads to a breakdown of fats, proteins, and carbohydrate stores and interference with immune function. This can delay wound healing and may increase the risk of systemic inflammatory response syndrome (SIRS)/sepsis and postoperative complications. Minimally invasive surgery can attenuate this response. Our purpose was (1) to compare neuroendocrine responses in patients undergoing open abdominal aneurysm repair with those in patients undergoing endovascular aneurysm repair (EVAR), (2) to compare the incidence of SIRS/sepsis and all complications in these two groups, and (3) to look at the relationship between procedure type, neuroendocrine response, and incidence of SIRS/sepsis and complications. METHODS: Forty-six patients who underwent open repair and 19 who underwent EVAR were studied. A baseline (T1) 24-hour urine save was undertaken in the week before admission, and a second 24-hour save (T2) commenced at anesthetic induction to measure cortisol and catecholamines. The incidences of SIRS/sepsis and complications were recorded. RESULTS: Significant ( P