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Safety and feasibility of upper limb cardiopulmonary exercise test in Friedreich ataxia

This study aims to explore the feasibility of upper limbs cardiopulmonary exercise test (CPET) in Friedreich ataxia (FRDA) patients and to compare the results with sex, age, and body mass index (BMI) matched cohort of healthy controls (HC). Cardiopulmonary exercise test was performed using an upper limbs cycle ergometer on fasting subjects. Peak oxygen uptake (peak VO2) was recorded as the mean value of VO2 during a 20 s period at the maximal effort of the test at an appropriate respiratory exchange rate. The ventilatory anaerobic threshold (AT) was detected by the use of the V-slope method. The investigators performed echocardiography with an ultrasound system equipped with a 2.5 MHz multifrequency transducer for complete M-mode, two-dimensional, Doppler, and Tissue Doppler Imaging analyses. 55 FRDA and 54 healthy matched controls (HC) were studies. Peak VO2 showed a significant 31% reduction in FRDA patients compared to HC (15.2 ± 5.7 vs. 22.0 ± 6.1 mL/kg/min; P < 0.001). Peak workload was reduced by 41% in FRDA (42.9 ± 12.5 vs. 73.1 ± 21.2 W; P < 0.001). In FRDA patients, peak VO2 is inversely correlated with the Scale for Assessment and Rating of Ataxia score, disease duration, and 9HPT performance, and directly correlated with activities of daily living. The AT occurred at 48% of peak workload time in FRDA patients and at 85% in HC (P < 0.001). Upper limb CPET is useful in the assessment of exercise tolerance and a possible tool to determine the functional severity of the mitochondrial oxidative defect in patients with FRDA. The cardiopulmonary exercise test is an ideal functional endpoint for Phases II and III trials through a simple, non-invasive, and safe exercise test.

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