Absolute Claudication Distance Research Articles

Narrative Review: Peripheral Arterial Disease in Patients with Hyperuricemia and Gout.

To discuss what is currently known about the association and potential mechanistic interactions of hyperuricemia and gout with peripheral arterial disease (PAD). Gout patients are at increased risk for coronary artery disease, but less is known about their risk for PAD. Studies suggest that the presence of gout and hyperuricemia are associated with PAD independent of known established risk factors. Moreover, higher SU was found to be associated with greater odds of having PAD and was independently associated with decreased absolute claudication distance. Urate's role in free radical formation, platelet aggregation, vascular smooth muscle proliferation, and impaired endothelial vasodilation may promote atherosclerotic progression. Studies suggest that patients with hyperuricemia or gout are at higher risk for developing PAD. Evidence is stronger for the relationship between elevated SU and PAD than for gout and PAD, but more data is needed. Whether elevated SU serves as a marker or cause of PAD remains to be investigated.

Propionyl-L-carnitine for intermittent claudication.

Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis. Intermittent claudication is a symptomatic form of PAD that is characterized by pain in the lower limbs caused by chronic occlusive arterial disease. This pain develops in a limb during exercise and is relieved with rest. Propionyl-L-carnitine (PLC) is a drug that may alleviate the symptoms of PAD through a metabolic pathway, thereby improving exercise performance. The objective of this review is to determine whether propionyl-L-carnitine is efficacious compared with placebo, other drugs, or other interventions used for treatment of intermittent claudication (e.g. exercise, endovascular intervention, surgery) in increasing pain-free and maximum walking distance for people with stable intermittent claudication, Fontaine stage II. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov trials register to July 7, 2021. We undertook reference checking and contact with study authors and pharmaceutical companies to identify additional unpublished and ongoing studies. Double-blind randomized controlled trials (RCTs) in people with intermittent claudication (Fontaine stage II) receiving PLC compared with placebo or another intervention. Outcomes included pain-free walking performance (initial claudication distance - ICD) and maximal walking performance (absolute claudication distance - ACD), analyzed by standardized treadmill exercise test, as well as ankle brachial index (ABI), quality of life, progression of disease, and adverse events. Two review authors independently selected trials, extracted data, and evaluated trials for risk of bias. We contacted study authors for additional information. We resolved any disagreements by consensus. We performed fixed-effect model meta-analyses with mean differences (MDs) and 95% confidence intervals (CIs). We graded the certainty of evidence according to GRADE. We included 12 studies in this review with a total number of 1423 randomized participants. A majority of the included studies assessed PLC versus placebo (11 studies, 1395 participants), and one study assessed PLC versus L-carnitine (1 study, 26 participants). We identified no RCTs that assessed PLC versus any other medication, exercise, endovascular intervention, or surgery. Participants received PLC 1 grams to 2 grams orally (9 studies) or intravenously (3 studies) per day or placebo. For the comparison PLC versus placebo, there was a high level of both clinical and statistical heterogeneity due to study size, participants coming from different countries and centres, the combination of participants with and without diabetes, and use of different treadmill protocols. We found a high proportion of drug company-backed studies. The overall certainty of the evidence was moderate. For PLC compared with placebo, improvement in maximal walking performance (ACD) was greater for PLC than for placebo, with a mean difference in absolute improvement of 50.86 meters (95% CI 50.34 to 51.38; 9 studies, 1121 participants), or a 26% relative improvement (95% CI 23% to 28%). Improvement in pain-free walking distance (ICD) was also greater for PLC than for placebo, with a mean difference in absolute improvement of 32.98 meters (95% CI 32.60 to 33.37; 9 studies, 1151 participants), or a 31% relative improvement (95% CI 28% to 34%). Improvement in ABI was greater for PLC than for placebo, with a mean difference in improvement of 0.09 (95% CI 0.08 to 0.09; 4 studies, 369 participants). Quality of life improvement was greater with PLC (MD 0.06, 95% CI 0.05 to 0.07; 1 study, 126 participants). Progression of disease and adverse events including nausea, gastric intolerance, and flu-like symptoms did not differ greatly between PLC and placebo. For the comparison of PLC with L-carnitine, the certainty of evidence was low because this included a single, very small, cross-over study. Mean improvement in ACD was slightly greater for PLC compared to L-carnitine, with a mean difference in absolute improvement of 20.00 meters (95% CI 0.47 to 39.53; 1 study, 14 participants) or a 16% relative improvement (95% CI 0.4% to 31.6%). We found no evidence of a clear difference in the ICD (absolute improvement 4.00 meters, 95% CI -9.86 to 17.86; 1 study, 14 participants); or a 3% relative improvement (95% CI -7.4% to 13.4%). None of the other outcomes of this review were reported in this study. When PLC was compared with placebo, improvement in walking distance was mild to moderate and safety profiles were similar, with moderate overall certainty of evidence. Although In clinical practice, PLC might be considered as an alternative or an adjuvant to standard treatment when such therapies are found to be contraindicated or ineffective, we found no RCT evidence comparing PLC with standard treatment to directly support such use.

Physical Activity Impacts Walking Distances and Energy Consumption of Patients with Peripheral Artery Disease

Lower extremity peripheral artery disease (PAD) is attributed to buildup of atherosclerotic plaques preventing adequate blood flow, leading to pain during walking, and ultimately physical inactivity. Normal day-to-day levels of physical activity may impact the distance a subject can walk before claudication pain onset, as well as their energy consumption capabilities. This study compared walking performance (initial claudication distance (ICD) and absolute claudication distance (ACD)), and energy consumption (EC) between active and inactive subjects with PAD. The distinction between groups was made using previous research that declared the average PAD patient walks 3586 steps/day. Ten subjects were classified as active (□3586 average steps/day) and sixteen participants as inactive (<3586 steps/day) based on a 7-day accelerometer measurement. The Gardner progressive treadmill test was used to asses ICD, ACD, and EC. EC was measured using a metabolic cart and calculated from the second minute of walking and the last minute prior to stopping due to claudication pain. The average ICD and ACD for the active group were 130.6±106.7 meters and 306.0±184.7 meters, respectively and 143.8±119.0 meters and 248.0±156.0 meters, respectively for the inactive group. The average EC for the second minute and last minute were 9.6±1.9 mlkg-1min-1 and 11.5±2.4 mlkg-1min-1 respectively for active group and 7.0±3.1 mlkg-1min-1 and 8.1±3.8 mlkg-1min-1 respectively for inactive group. The data suggests that the active group had better walking performance and greater energy consumption indicating increased efficiency of oxygen transport and extraction capability in the leg muscles.

Cilostazol for intermittent claudication.

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(exercise-induced lower limb pain relieved by rest).Thesepatients have a three- to six-fold increase in cardiovascular mortality. Cilostazol is a drug licensed for the use of improving claudication distance and, if shown to reduce cardiovascular risk,could offer additional clinical benefits. This is an update of the review first published in 2007. To determine the effect of cilostazolon initial and absolute claudication distances, mortality and vascular events in patients with stable intermittent claudication. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and AMED databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries, on 9 November 2020. We considered double-blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other drugs used to improve claudication distance in patients with stable intermittent claudication. Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We assessed the risk of bias with the Cochrane risk of bias tool. Certainty of the evidence was evaluated using GRADE. For dichotomous outcomes, we used odds ratios (ORs) with corresponding 95% confidence intervals (CIs) and for continuous outcomes we used mean differences (MDs) and 95% CIs. We pooled data using a fixed-effect model, or a random-effects model when heterogeneity was identified. Primary outcomes were initial claudication distance (ICD) and quality of life (QoL). Secondary outcomes were absolute claudication distance (ACD), revascularisation, amputation, adverse events and cardiovascular events. We included 16 double-blind, RCTs (3972 participants) comparing cilostazol with placebo, of which five studies also compared cilostazol with pentoxifylline. Treatment duration ranged from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Cilostazol dose ranged from 100 mg to 300 mg; pentoxifylline dose ranged from 800 mg to 1200 mg. The certainty of the evidence was downgraded by one level for all studies because publication bias was strongly suspected. Other reasons for downgrading were imprecision, inconsistency and selective reporting. Cilostazol versus placebo Participants taking cilostazol had a higher ICD compared with those taking placebo (MD 26.49 metres; 95% CI 18.93 to 34.05; 1722 participants; six studies; low-certainty evidence). We reported QoL measures descriptively due to insufficient statistical detail within the studies to combine the results; there was a possible indication in improvement of QoL in the cilostazol treatment groups (low-certainty evidence). Participants taking cilostazol had a higher ACD compared with those taking placebo (39.57 metres; 95% CI 21.80 to 57.33; 2360 participants; eight studies; very-low certainty evidence). The most commonly reported adverse events were headache, diarrhoea, abnormal stools, dizziness, pain and palpitations. Participants taking cilostazol had an increased odds of experiencing headache compared to participants taking placebo (OR 2.83; 95% CI 2.26 to 3.55; 2584 participants; eight studies; moderate-certainty evidence).Very few studies reported on other outcomes so conclusionson revascularisation, amputation, or cardiovascular events could not be made. Cilostazol versus pentoxifylline There was no difference detected between cilostazol and pentoxifylline for improving walking distance, both in terms of ICD (MD 20.0 metres, 95% CI -2.57 to 42.57; 417 participants; one study; low-certainty evidence); and ACD (MD 13.4 metres, 95% CI -43.50 to 70.36; 866 participants; two studies; very low-certainty evidence). One study reported on QoL; the study authors reported no difference in QoL between the treatment groups (very low-certainty evidence). No study reported on revascularisation, amputation or cardiovascular events. Cilostazol participants had an increased odds of experiencing headache compared with participants taking pentoxifylline at 24 weeks (OR 2.20, 95% CI 1.16 to 4.17; 982 participants; two studies; low-certainty evidence). Cilostazol has been shown to improve walking distance in people with intermittent claudication. However, participants taking cilostazol had higher odds of experiencing headache. There is insufficient evidence about the effectiveness of cilostazol for serious events such as amputation, revascularisation, and cardiovascular events. Despite the importance of QoL to patients, meta-analysis could not be undertaken because of differences in measures used and reporting. Very limited data indicated no difference between cilostazol and pentoxifylline for improving walking distance and data weretoo limited for any conclusions on other outcomes.

Correlation between severity of spinal stenosis and multifidus atrophy in degenerative lumbar spinal stenosis

BackgroundDegenerative lumbar spinal stenosis (DLSS) is a common degenerative condition in older adults. Muscle atrophy (MA) is a leading cause of muscle weakness and disability commonly reported in individuals with spinal stenosis. The purpose of this study was to investigate if the MA correlates with the grade of spinal stenosis in patients with DLSS.MethodsA retrospective analysis on 48 male and 184 female DLSS patients aged around 54.04 years (54.04 ± 8.93) were involved and divided into 6 groups according to claudication-distance-based grading of spinal stenosis, which confirmed by two independent orthopedic surgeons using T2- weighted images. Using 1.5T MRI scanner, the severity of MA is assessed based on its negative correlation with the ratio of total fat-free multifidus muscle cross-sectional area (TFCSA) to total multifidus muscle cross-sectional area (TCSA). Adobe Photoshop CS6 was used for qualitative image analysis and calculate the TFCSA/TCSA ratio to assess the severity of MA, compare the grade of MA with the spinal stenosis segment, stenosis grade and symptom side.ResultsIn DLSS group, The TFCSA/TCSA ratio are 74.33 ± 2.18 in L3/4 stenosis, 75.51 ± 2.79 in L4/5 stenosis, and 75.49 ± 2.69 in L5/S1 stenosis. there were significant decreases in the TFCSA/TCSA ratio of stenotic segments compared with non-stenotic segments of the spinal canal (P < 0.05) while no significant difference between the non-stenotic segments (P > 0.05). TFCSA/TCSA ratios is significant differences in the TFCSA/TCSA ratios of the 6 DLSS groups (F = 67.832; P < 0.05). From Group 1 to Group 6, the TFCSA/TCSA ratio of stenotic segments positively correlated with the absolute claudication distance (ACD). (P < 0.001, r = 0.852). Besides, the TFCSA/TCSA ratios are smaller in the symptomatic sides of the spine than the contralateral sides (t = 4.128, P = 0.001).ConclusionsThe stenotic segments of the spinal canal are more atrophied than the non-stenotic segment in DLSS patients. It is shows that a strong positive correlation between the severity of multifidus atrophy and the severity of spinal stenosis.

Intermittent Administration of Nitroglycerin Sublingual Powder Compared with Placebo in Outpatients with Peripheral Artery Disease: Results of a Randomised Proof of Concept Study

Treatment of peripheral artery disease (PAD), Fontaine Stage IIb with vasoactive substances is of limited efficacy and does not last beyond the active treatment. Glyceryl trinitrate (GTN) is a vasodilating agent that relaxes vascular smooth muscle cells. The aim was to prove the concept that GTN sublingual powder has sustained clinical efficacy and adequate safety in these patients. This was a multicentre, randomised, double blind, placebo controlled, forced titration, proof of concept study (phase IIa). Patients had a treadmill test at baseline, after 12 weeks of GTN/placebo administration, and at 19 and 26 weeks (without treatment). Primary objectives were an increase in initial claudication distance (ICD) and absolute claudication distance (ACD) at 12 weeks. Ninety-five patients were screened and 73 randomised, of which 53 patients completed the 12 week treatment phase (GTN 26, placebo 27). At a baseline ICD of 59.2±32.8m (GTN) and 57.5±39.7m (placebo), GTN led to a placebo corrected ICD increase of 23.2% vs. baseline (p=.35). Baseline ACD was 105.3±52.9m (GTN) and 106.1±95.0m (placebo), and GTN led to a placebo corrected increase of 3.6% (p=.44), with substantial interindividual variation. The change in claudication distance was greater in patients with an ICD of ≥50m at baseline (ΔICD 29.3%; p=.19), and an ACD≥100m (ΔACD 8.5%; p=.40). The effect lasted beyond the active treatment period as shown by a 49.3% increase in ICD (p=.31) and a 20.6% increase in ACD (p=.21) by week 26. GTN sublingual powder was well tolerated. Intermittent treatment with nitroglycerin sublingual powder may represent a potential treatment option for patients with PAD stage Fontaine IIb, with an immediate and a sustained effect. The observed increases in ACD and ICD were however not statistically significant in this phase IIa proof of concept study. Further studies are required.

Effects of Physical Rehabilitation on Spatiotemporal Gait Parameters and Ground Reaction Forces of Patients with Intermittent Claudication.

Chronic ischemia of the lower extremities often presents as intermittent claudication characterized by lower limb pain which subsides after a short break. This study aimed to provide an assessment of the spatiotemporal parameters of gait and ground reaction forces in patients with PAD participating in three forms of supervised physical training. A total of 80 subjects completed a three-month supervised physical rehabilitation program with three sessions per week. The subjects were assigned to one of three programs: group 1—standard walking training on a treadmill (TT); group 2—Nordic walking (NW) training; group 3—strength and endurance training comprised of NW with isokinetic resistance training (NW + ISO). Gait biomechanics tests (kinematic and kinetic parameters of gait) and a six-minute walk test were carried out before and after three months of physical training. Nordic walking training led to the greatest improvements in the gait pattern of patients with PAD and a significant increase in the absolute claudication distance and total gait distance. Combined training (NW + ISO) by strengthening the muscles of the lower extremities increased the amplitude of the general center of gravity oscillation to the greatest extent. Treadmill training had little effect on the gait pattern. Nordic walking training should be included in the rehabilitation of patients with PAD as a form of gait training, which can be conducted under supervised or unsupervised conditions.

Impact Of An Ankle-foot Orthosis On Physical Activity In Patients With Peripheral Artery Disease

Patients with peripheral artery disease (PAD) are sedentary due to claudication pain in the lower extremities. Our research has documented an inability of the ankle plantarflexors to generate normal push-off during walking. An ankle-foot orthosis (AFO) to offset push-off deficiency may improve physical activity levels and walking distances in patients with PAD. PURPOSE: To compare step count (SC), peak activity index (PAI), initial claudication distances (ICD), and absolute claudication distances (ACD) before and after an AFO intervention. METHODS: Six patients with PAD (Age: 71.7 ± 9.3 years; Body Mass Index: 27.5 ± 5.5 kg/m2) were enrolled in the study. They underwent measurements of SC and PAI over a week using an accelerometer. ICD and ACD were determined while subjects performed the Gardner treadmill protocol without wearing AFOs. All measures were assessed before and after the three month AFO intervention. Signed Rank tests were performed to determine differences following the intervention. RESULTS: ACD was significantly increased following the AFO intervention (p=0.046). Mean ACD was 312 ± 169 meters at baseline and increased to 364 ± 194 meters after the three month AFO intervention. Measures before and after the AFO intervention of SC (2422 ± 1166 steps/day and 2349 ± 1112 steps/day), PAI (34 ± 13 steps/min and 30 ± 7 steps/min), and ICD (187 ± 111 meters and 173 ± 138 meters) were not significantly different. CONCLUSION: The preliminary results of this study indicated that the AFO intervention improves the ACD in patients with PAD while walking without AFO. Future work should increase the number of subjects and determine whether physical activity intensity levels (light, moderate, and vigorous) changed after AFO intervention. Supported by NIH Grant HD090333-01. We acknowledge Alex Dzewaltowski, Cody Anderson, and Kaeli Samson for supporting this study.

Interferential Electrical Stimulation Versus Pulsed Electro-Magnetic Field in Management of Intermittent Claudication

Background: Intermittent claudication is the occurrence of leg pain, aching, cramping, or fatigue triggered by walking and relieved by rest. It's a chronic disabling condition and the first symptom of peripheral arterial disease (PAD). Objective: This study was designed to compare between the therapeutic efficacy of Interferential electrical stimulation and pulsed electromagnetic field (PEMF) in management of intermittent claudication (IC). Subjects and methods: Forty five patients suffering from intermittent claudication due to atherosclerosis (Fontain stage II PAD) and randomly were assigned into three equal groups. Group “A” included 15 patients received 30 min of pulsed electromagnetic field in addition to heel raise exercise and calf stretch exercise and their medical treatment, group “B” included 15 patients received 20 min of interferential electrical stimulation in addition to heel raise exercise and calf stretch exercise and group “C” (control group) that included 15 patients received their medical treatment only. Ankle brachial pressure index, graded treadmill exercise testing to determine absolute claudication distance (ACD), Peak walking time (PWT) and walking impairment questionnaire (distance score, speed score, symptoms impairment score) were recorded pre and post the two months period for all groups. Results: All measured parameters were significantly improved in all groups with the greatest improvement was in group (A) and the least improvement was in group (C) except for ankle brachial index that was changed significantly in group (A) only. Conclusion: PEMF could be an effective vascular rehabilitation modality for improving walking efficiency and functional capacity in patients with intermittent claudication. It significantly increases the blood flow in peripheral arteries and so on can delay the complications of intermittent claudication.

Effects of Intermittent Calf Muscle Electrical Stimulation on Walking Capacity in Claudicants Living with Type 2 Diabetes.

First-line therapy for diabetic patients presenting with intermittent claudication includes supervised exercise programs to improve walking distance. However, exercise comes with a variety of barriers and may be contraindicated in certain conditions. The aim of this study was to evaluate whether calf muscle electrostimulation improves claudication distance. A prospective, one-group, pretest-posttest study design was used on 40 participants living with type 2 diabetes mellitus, peripheral artery disease (ankle brachial pressure index, <0.90), and calf muscle claudication. Calf muscle electrostimulation of varying frequencies (1-250 Hz) was prescribed on both limbs for 1-hour daily sessions for 12 consecutive weeks. The absolute claudication distance (ACD) was measured at baseline and after the intervention. The recruited cohort (30 men and ten women; mean age, 71 years; mean ankle brachial pressure index, 0.70) registered a mean ± SD baseline ACD of 333.71 ± 208 m. After a mean ± SD of 91.68 ± 6.23 days of electrical stimulation, a significant mean ± SD increase of 137 ± 136 m in the ACD (P = .001, Wilcoxon signed rank test) was registered. Improvement was found to be sex independent, but age was negatively correlated with proportion of improvement (r = -0.361; P = .011, Pearson correlation test). Electrical stimulation of varying frequencies on ischemic calf muscles significantly increased the maximal walking capacity in claudicants with type 2 diabetes. This therapeutic approach should be considered in patients with impaired exercise tolerance or as an adjunct treatment modality.

Long-term efficacy of a home-based training program coupled to education for patients with intermittent claudication

There are emerging evidences of efficacy of home-based exercise programs for peripheral artery disease (PAD) patients who suffer from intermittent claudication (IC), especially when they are coupled with educational programs (HEP - EPs). We have previously reported the positive one-year results of a specific 3 months home-based exercise program combined with therapeutic education. In this work, we aimed to evaluate the long-term effect of this program (24 months) in walking distance improvement. The secondary objective of the study was to evaluate the long-term results of our program for patients with aorto-iliac lesions. Patients with an ankle-brachial index (ABI) below 0.9 in at least one limb, and an absolute claudication distance (ACD) ≤ 500 meters, were included in the study. During the first three months, patient participated to an educational program with educational workshop, and a weekly telephone coaching. In educational session patients were assisted in delimiting walking objectives. Functional parameters were evaluated at 0, 12, and 24 months. Between Feb 2014 and Jan 2019, 112 and 39 PAD patients with IC completed the 12- and 24-month follow-up, respectively. More than a third of the population (42 patients) had significant aorto-iliac artery lesions. In both the overall population and the group of patients with aorto-iliac lesions, the mean initial claudication distance (ICD) increased by 3 times and the mean absolute claudication distance (ACD) by 2, compared to baseline values at 24-month follow-up ( Fig. 1 ). The results of our study indicate that home-based training combined with therapeutic educational programs for patients with PAD who suffer from IC, have a clear long-term beneficial effect in walking performance at 24 months. Patients with aorto-iliac disease can benefit equally from this program than patients with femoral lesions.

Efficacy and Feasibility of Pain management and Patient Education for Physical Activity in Intermittent claudication (PrEPAID): protocol for a randomised controlled trial

BackgroundPhysical activity (PA) improves functional capacity and quality of life and provides secondary prevention benefits in individuals with peripheral arterial disease (PAD) and intermittent claudication (IC). However, pain and patient lack of knowledge are key barriers to the uptake of, and adherence to, PA recommendations. This trial will test the efficacy and feasibility of a non-invasive pain management intervention with and without patient education to improve PA in individuals with PAD and IC.MethodsThis is a randomised, controlled assessor-blinded feasibility trial with four parallel groups. Eighty adults with PAD and IC will be randomly assigned 1:1:1:1 to Active TENS (transcutaneous electrical nerve stimulation), Placebo TENS, Active TENS + Patient education or Placebo TENS + Patient education groups. All groups will continue to receive usual care over the intervention period. Participants randomised to Active TENS will receive a TENS device (preset at 120 Hz, 200 μs) and will be instructed to use the device daily at home or elsewhere for 6 weeks with a patient-determined intensity of “strong but comfortable”. Placebo TENS group participants will receive the same model of TENS device and instructions for use as those in the active group, except that the stimulation dose will be safely altered to produce non-therapeutic, ineffective stimulation. Participants randomised to patient education will receive a one-off 3-h workshop of structured group education (four to five persons in each group) and three sets of twice-weekly phone calls. Efficacy outcomes will be assessed at baseline, after 6 weeks of intervention and at 3 months follow-up. Absolute claudication distance using the Gardner treadmill protocol will be assessed as the primary outcome. Secondary outcomes will assess initial claudication distance, daily PA and patient-reported outcomes including quality of life, pain self-efficacy, depression, disease perception and walking impairment pain intensity and quality. Feasibility outcomes will assess rates of recruitment, retention and adherence. Focus groups with participants at the end of the trial will explore the acceptability of the interventions.DiscussionThis trial will determine the efficacy and feasibility of using a low-cost, CE-marked non-invasive pain management modality delivered with or without a patient-centred education intervention to improve PA in individuals with PAD and IC.Trial registrationClinicalTrials.gov, NCT03204825. Registered on 2 July 2017.

Venous Return Assist Devices for Intermittent Claudication: A Randomized Controlled Trial Utilizing a Sham Comparator

Objectives: To determine whether an intermittent mechanical compression device (Venowave) effects walking distance in patients with intermittent claudication as compared to placebo, as well as to review the published literature on the topic. Design: Randomized, cross-over, blinded trial of an intermittent mechanical compression device (Venowave), compared with a sham compression device. Setting: Hamilton Health Sciences, Hamilton, Canada. Participants: 27 patients with severe peripheral limb ischemia, as identified by at least one of: i) ABI<0.4; ii) ACD<200 m (Fontaine stage IIb); iii) toe-brachial index<0.5; or iv) toe pressure<40 mmHg or rest pain due to arterial ischemia. Main Outcome Measures: The primary outcome measure was Absolute Claudication Distance (ACD) while walking on a treadmill. Secondary outcome measures included Initial Claudication Distance (ICD), walk time measured in minutes, and a modified version of the Walking Impairment Questionnaire (WIQ). Results: There was no significant difference in ACD (mean difference: 14.1 m; 95% CI: -31.6 m-59.9 m; p=0.53) or ICD (mean difference: 5.9 m; 95% CI: -26.3 m-14.5 m; p=0.55) between active and sham devices. Mean walk time was identical between active and sham devices (5.6 minutes (2.1) vs. 5.6 minutes (2.0); p=0.99). The modified WIQ score was higher in the active group compared with the sham group (mean difference 2.1 m; 95% CI: 0.3 m-3.9 m; p=0.03). Conclusion: In patients with moderate to severe intermittent claudication, the Venowave device did not increase walking distance when used immediately prior to and during measured effort. This is the first study to use a sham device as a comparator in this specific context.

The effects of dietary flaxseed on cardiac arrhythmias and claudication in patients with peripheral arterial disease 1.

Patients with peripheral artery disease (PAD) are at increased risk for cardiovascular events, and higher susceptibility for cardiac arrhythmias may be involved. The objectives of this double-blinded randomized controlled FLAX-PAD trial were to determine whether daily consumption of a diet supplemented with 30 g of milled flaxseed (or placebo) over 1 year by PAD patients has effects on the prevalence of cardiac arrhythmias and exercise capacity. Cardiac arrhythmias were assessed on a cardiac stress test and at rest. At baseline, the PAD patients had a high incidence of cardiac arrhythmias (48% in the flaxseed group and 32% in the placebo group). After 1 year, the presence of cardiac arrhythmias in the flaxseed group decreased by 2% and increased by 12% in the placebo group (P > 0.05). Electrocardiographic variables (P, PR, QRS, QT, and QTc) did not change in either group during the trial. Patients from both groups improved initial and absolute claudication distances but the intergroup difference was also not statistically significant. In summary, the prevalence of cardiac arrhythmias and physical capacity trended in a positive direction for patients ingesting flaxseed but either a larger sample size or a longer intervention with flaxseed may be required to show statistically significant differences.

Three-curve rocker-soled shoes and gait adaptations to intermittent claudication pain: A randomised crossover trial

BackgroundIntermittent claudication (IC) is a symptom of peripheral arterial disease where a cramp-like leg pain is exhibited during walking, which affects gait and limits walking distance. Specifically-designed rocker-soled shoes were purported to mechanically unload the calf musculature and increase walking distances until IC pain. Research questionsDo three-curve rocker-soled shoes increase walking distance and what are the biomechanical differences during pain-free walking and IC pain-induced walking, when compared with control shoes? MethodsFollowing NHS ethical approval, 31 individuals with claudication (age 69 ± 10 years, stature 1.7 ± 0.9 m, mass 83.2 ± 16.2 kg, ankle-brachial pressure index 0.55 ± 0.14) were randomised in this cross-over trial. Gait parameters whilst walking with rocker-soled shoes were compared with control shoes at three intervals of pain-free walking, at onset of IC pain (initial claudication distance) and when IC intensifies and prevents them walking any further (absolute claudication distance). Two-way repeated measures ANOVA were performed on gait variables. ResultsWhen compared with control shoes, rocker-soled shoes reduced ankle power generation (mean 2.1 vs 1.6 W/kg, respectively; p = 0.006) and altered sagittal kinematics of the hip, knee and ankle. However, this did not translate to a significant increase in initial (138 m vs 146 m, respectively) or absolute (373 m vs 406 m, respectively) claudication distances. In response to IC pain, similar adaptations in temporal-spatial parameters and the sagittal kinematics were observed between the shoe types. SignificanceThe three-curved rocker shoes, in their current design, do not augment gait sufficiently to enhance walking distance, when compared with control shoes, and therefore cannot be recommended for the intermittent claudication population.Clinical Reg No. (ClinicalTrials.gov): NCT02505503.

Effect of cilostazol on claudication distances and lipid profile in patients with occlusive peripheral arterial disease: A placebo controlled trial

Objectives(s): To study the efficacy and tolerability of cilostazol in patients with moderately severe peripheral arterial disease.&#x0D; Study Design: Randomized, open label, placebo controlled parallel study.&#x0D; Methods: It is a prospective, randomized, open label, placebo controlled parallel study conducted in Postgraduate Department of Pharmacology and Therapeutics in collaboration with Cardiothoracic and Vascular Surgery Department, Govt. Medical College Jammu for a period of one year.&#x0D; Results: Out of 53 patients fulfilling the inclusion criteria, 28 patients were assigned cilostazol 100mg twice daily, and 25 patients were given placebo twice daily. Cilostazol significantly raised both initial as well as absolute claudication distance, which was well sustained throughout all weeks of follow up, whereas placebo raised he claudication distance for initial few weeks, but decreased it below baseline subsequently. Cilostazol also had significant beneficial effect on lipid profile compared to placebo. There was almost no significant difference in patient’s assessment, physician’s assessment as well as side effect between two groups.&#x0D; Conclusion: Cilostazol can be an effective treatment for patients of peripheral arterial disease with intermittent claudication. It also has favorable effect on lipid profile. However, long term randomized trials on large scale are required to further substantiate our findings. JMS 2017;20(2):77-81

The Effectiveness of Calf Muscle Electrostimulation on Vascular Perfusion and Walking Capacity in Patients Living With Type 2 Diabetes Mellitus and Peripheral Artery Disease.

The aim of the study was to explore calf muscle electrostimulation on arterial inflow and walking capacity in claudicants with peripheral artery disease and diabetes mellitus. A prospective, 1-group, pretest-posttest study design was used on 40 high-risk participants (n = 40) who exhibited bilateral limb ischemia (ankle brachial pressure index [ABPI] <0.90), diabetes mellitus, and calf muscle claudication. A program of calf muscle electrical stimulation with varying frequency (1-250 Hz) was prescribed for 1 hour per day for 12 weeks. Spectral waveforms analysis, ABPI, absolute claudication distance (ACD), and thermographic temperature patterns across 4 specified regions of interest (hallux, medial forefoot, lateral forefoot, heel) at rest and after exercise, were recorded at baseline and following intervention to evaluate for therapeutic outcomes. A significant improvement in ACD and ABPI was registered following the intervention ( P = .000 and P = .001, respectively). Resting foot temperatures increased significantly ( P = .000) while the postexercise temperature drops were halved across all regions at follow-up, with hallux ( P = .005) and lateral forefoot ( P = .038) reaching statistical significance. Spectral Doppler waveforms were comparable ( P = .304) between both serial assessments. Electrical stimulation of varying frequency for 1 hour per day for 12 consecutive weeks registered statistically significant improvement in outcome measures that assess arterial inflow and walking capacity in claudicants with diabetes mellitus. These results favor the use of electrostimulation as a therapeutic measure in this high-risk population.

A comparative study of cilostazol and pentoxifylline in intermittent claudication in peripheral arterial disease

Aims: A comparative study of Cilostazole and Pentoxifylline on intermittent claudication in patients of peripheral arterial disease. Materials and Methods: A total of 70 patients clinically proven occlusive peripheral arterial disease admitted at wards of General Surgery at Acharya Vinoba Bhave Rural Hospital, Sawangi, Wardha. It was prospective study the patients were randomized in two groups in 1:1 ratio. The randomization was done using a random allocation sequence generated by computer program and sequential patient consenting to participate in the study was allocated in the respective treatment arms - Cilostazole and Pentoxyphylline per the allocation sequence. Group I Patients (n=35) were administered Tab. Pentoxifylline 400 mg thrice a day; Group II (n=35), Tab Cilostazol 100 mg twice a day. History, clinical examination, all routine investigation including lipid profile, color Doppler study of lower limb and Angiography of lower limb vessels was performed at the start of the trial. Patients were re-evaluated at the time of enrolment and at 24 weeks for Intermittent Claudication Distance (ICD), Absolute Claudication Distance (ACD), and Ankle Brachial Index (ABI). Results: The group II (Cilostazole Group) showed more rise in intermittent claudication distance and Acute Claudication Distance as compared to Pentoxifylline. There was also statically improvement in ankle brachial index of Group II (Cilostazole Group) as compared to Group I (Pentoxifylline). Conclusion: Thus, the comparative analysis revealed that the efficacy of Cilostazole is more than the Pentoxifylline in increasing the ICD and ACD in patients of occlusive peripheral arterial disease with stable intermittent claudication in patients of peripheral arterial disease.

Transcutaneous calf-muscle electro-stimulation: A prospective treatment for diabetic claudicants?

First-line therapy for claudicants with diabetes include supervised exercise programmes to improve walking distance. However, exercise comes with a number of barriers and may be contraindicated in certain conditions. The aim of this study was to evaluate whether calf-muscle electro-stimulation improves claudication distance. A prospective, one-group, pretest-posttest study design was employed on 40 participants living with type 2 diabetes mellitus, peripheral artery disease (ankle-brachial pressure index < 0.90) and calf-muscle claudication. Calf-muscle electro-stimulation of varying frequencies (1-250 Hz) was applied on both ischaemic limbs (N = 80) for 1 h per day for 12 consecutive weeks. The absolute claudication distance was measured at baseline and following the intervention. The cohort (n = 40; 30 males; mean age = 71 years; mean ankle-brachial pressure index = 0.70) registered a mean baseline absolute claudication distance of 333.71 m (standard deviation = 208). Following 91.68 days (standard deviation = 6.23) of electrical stimulation, a significant mean increase of 137 m (standard deviation = 136) in the absolute claudication distance was registered (p = 0.000, Wilcoxon signed rank test). Electrical stimulation of varying low to high frequencies on ischaemic calf muscles significantly increased the maximal walking capacity in claudicants with type 2 diabetes. This therapeutic approach may be considered in patients with impaired exercise tolerance or as an adjunct treatment modality.

Transcutaneous Electrical Nerve Stimulation Improves Walking Performance in Patients With Intermittent Claudication.

The purpose of this study was to investigate the effects of 2 types of transcutaneous electrical nerve stimulation (TENS) on walking distance and measures of pain in patients with peripheral arterial disease (PAD) and intermittent claudication (IC). In a phase 2a study, 40 participants with PAD and IC completed a graded treadmill test on 2 separate testing occasions. Active TENS was applied to the lower limb on the first occasion; and placebo TENS, on the second. The participants were divided into 2 experimental groups. One group received high-frequency TENS; and the other, low-frequency TENS. Measures taken were initial claudication distance, functional claudication distance, and absolute claudication distance. The McGill Pain Questionnaire (MPQ) vocabulary was completed at the end of the intervention, and the MPQ-Pain Rating Index score was calculated. Four participants were excluded from the final analysis because of noncompletion of the experimental procedure. Median walking distance increased with high-frequency TENS for all measures (P < .05, Wilcoxon signed rank test, all measures). Only absolute claudication distance increased significantly with low-frequency TENS compared with placebo (median, 179-228; Ws = 39; z = 2.025; P = .043; r = 0.48). No difference was observed between reported median MPQ-Pain Rating Index scores: 21.5 with placebo TENS and 21.5 with active TENS (P = .41). Transcutaneous electrical nerve stimulation applied to the lower limb of the patients with PAD and IC was associated with increased walking distance on a treadmill but not with any reduction in pain. Transcutaneous electrical nerve stimulation may be a useful adjunctive intervention to help increase walking performance in patients with IC.