ABC | Volume 114, Nº3, March 2020

Original Article Farah et al. Effort during 6-minute walk test Arq Bras Cardiol. 2020; 114(3):486-492 Recruitment and Patients PAD patients classified as Rutherford Grade I and Category 1 to 3 were evaluated at the Clinical Research Center at the University of Oklahoma Health Sciences Center. Patients arrived fasted, but were permitted to take their usual medications. Patients were recruited by referrals from the Health Sciences Center vascular clinics, as well as by newspaper advertisements for possible enrollment into an exercise study. 14,15 However, patients were included in the study if they fully met the following criteria: (a) graded treadmill test limited by intermittent claudication symptoms and (b) an ankle brachial index (ABI) ≤ 0.90 at rest, or an ABI ≤ 0.73 after exercise. 1 Patients were excluded if they met any of the following criteria: (a) inability to obtain an ABI measure due to non‑compressible vessels (ABI ≥ 1.40), (b) asymptomatic PAD determined from their medical history and verified upon the graded treadmill test, (c) exercise tolerance during progressive treadmill test limited by factors other than claudication symptoms (e.g. clinically significant electrocardiographic changes during exercise indicative of myocardial ischemia, dyspnea, poorly controlled blood pressure), (d) failure to achieve VT during treadmill exercise, (e) inability to complete the 6-minute walk test without stopping, and (f) failure to complete the testing within three weeks. Study Design This study was divided into three steps: 1) clinical examination, 2) graded treadmill test, and, 3) 6-minute walk test. Step 1 included evaluations for medical history, anthropometry, and ankle-brachial index. During step 2, patients performed a progressive graded cardiopulmonary treadmill test until maximal claudication pain, in order to obtain the VT. In step 3, the 6-minute walk test was applied aiming to identify the patients who did not and those who did achieve VT (Figure 1). The details of all evaluations are described below. Medical History and Anthropometry Demographic information, height, weight, body mass index, waist circumference, claudication history, physical examination and comorbid conditions (osteoarthritis, obesity, hypertension, diabetes, dyslipidemia, metabolic syndrome and heart disease) were assessed at the beginning of the study by a physician. Obesity was defined as body mass index > 30 kg/m 2 . 16 Hypertension was defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg, or use of anti-hypertensive medication. 16 Diabetes was defined as fasting blood glucose ≥ 126 mg/dl, or use of hypoglycemic medication. 17 Dyslipidemia was defined as triglycerides ≥ 150 mg/dl, LDL-C≥ 130 mg/dl, total cholesterol ≥ 200 mg/dl or HDL-C ≤ 40 mg/dl (men) and ≤ 50 mg/dl (women), or use of lipid-lowering medication. 18 Metabolic syndrome was defined as three ormore of the following components: (1) abdominal obesity (waist circumference >102 cm in men and> 88 cm in women), (2) elevated triglycerides (>150 mg/dl), (3) reduced HDL-C (< 40 mg/dl in men and < 50 mg/dl in women), (4) elevated bloodpressure (>130/85mmHg), and (5) elevated fasting glucose (> 110 mg/dl), as well as diagnosis of diabetes. 19 Ankle Brachial Index ABI was obtained after 10 minutes of supine rest by measuring the ankle and brachial systolic blood pressure using Doppler technique in the brachial artery and both posterior tibial and dorsalis pedis arteries. The highest value between the two measurements of arterial pressure from each leg was recorded, and the leg yielding the lowest ABI was used in the analyses, as previously described. 20 Graded Treadmill Test A graded treadmill test was used to obtain the VT and to assess walking capacity. Patients performed a progressive graded cardiopulmonary treadmill test until maximal claudication pain, as previously described. 21 The test started at 2 mph with 0% grade and the workload was increased 2% every 2 minutes. All patients were informed of the test protocol before being submitted to it. Oxygen consumption (VO 2 ) was continuously measured by a metabolic cart (Medical Graphics Corp., St Paul, MN), and averages of 30s were applied for analysis. The VT was visually detected by two experienced evaluators and defined as a nonlinear increase in respiratory quotient, carbon dioxide production and ventilation, as well as the increase in end‑tidal oxygen pressure. The following variables were analyzed: oxygen uptake (VO 2 ), carbon dioxide output (VCO 2 ), ventilatory equivalent (VE), ventilatory equivalent for O 2 (VE/VO 2 ), ventilatory equivalent for CO 2 (VE/VO 2 ), end-tidal oxygen (PETO 2 ) and carbon dioxide partial pressures (PETCO 2 ), and respiratory exchange ratio, as previously described. 22 A third researcher compared the results to check possible discrepancies in the determination of VT between evaluators. In this case, the determination of VT was repeated by both evaluators and the third evaluator made the final determination. Patients not presenting any of these respiratory parameters during the progressive graded cardiopulmonary treadmill test were considered to not have achieved the VT and were therefore excluded from the sample. Claudication Measurements and Peak Oxygen Uptake The claudication onset time was defined as the walking time at which the patient first experienced leg pain during the treadmill test, and the peak walking time was defined as the walking time at which the patients could not continue walking due the leg pain. VO 2 peak was defined as the 30-second window with the highest VO 2 achieved during the treadmill test. Using these procedures, the test-retest intra-class reliability coefficients are r = 0.89 for claudication onset time and r = 0.93 for peak walking time. 24 6-minute Walk Test A trained technician administered the 6-minute walk test which was conducted in a 30-meter long corridor. Subjects were instructed to walk as many laps around the cones as possible while bearing a light weight (0.8 kg), portable oxygen uptake unit (COSMED K4 b 2 , COSMED USA, Inc, Chicago, IL) which continuously measured oxygen uptake via indirect calorimetry. The technician was blinded to the VT results, and the test was performed following the standardized instructions, as previously described. 23 VO 2 was obtained breath-by-breath and then 487