Cardiopulmonary exercise testing as an integrative approach to explore physiological limitations in Duchenne muscular dystrophy

Abstract

Background: Cardiopulmonary exercise testing (CPET) is the gold-standard for quantification of peak oxygen uptake (VO2) and cardiorespiratory and muscle responses to exercise. Its application to Duchenne muscular dystrophy (DMD) has been scarce due to the notion that muscle weakness inherent to disease restricts the cardiorespiratory system from reaching maximal capacity. Objective: To investigate the utility of CPET in DMD by 1) establishing whether patients can perform maximal-effort exercise for valid VO2 peak assessment; 2) quantifying VO2 peak repeatability; 3) characterizing muscle and cardiorespiratory responses; 4) comparing VO2 peak to 6-min walk distance (6MWD). Methods: Twenty-seven DMD and eight healthy boys (6 years and older) underwent CPET using an incremental work-rate protocol for leg (ambulatory) or arm (non-ambulatory) cycling with measurement of heart rate (HR) and gas-exchange variables from rest to maximal-effort. The oxygen cost of work (ΔVO2/Δwork-rate) was calculated, and peak exercise parameters (VO2, HR, O2 pulse, ventilation (VE) and ventilatory threshold (VT)) were considered valid if the respiratory exchange ratio ≥1.01. Results: VO2 peak was valid (81.5% of patients), repeatable (intraclass correlation coefficient = 0.998) and low in ambulatory and non-ambulatory DMD compared to controls (19.0 ± 6.0; 10.7 ± 2; 35.2 ± 4.5 mL/kg/min respectively). VT was low (30.8 ± 10.7; 19.4 ± 3.0; 61.2 ± 6.9% VO2 peak) reflecting significant muscle metabolic impairment. Peak HR in ambulatory-DMD (172 ± 14 bpm) was similar to controls (183 ± 8.3 bpm), but O2 pulse was low (3.4 ± 1.0; 6.5 ± 1.1 mL/beat). Peak VE/VO2 (ambulatory = 42.1 ± 6.8; non-ambulatory = 42.2 ± 7.8; controls = 34.3 ± 4.6) and ΔVO2/Δwork-rate were elevated (ambulatory = 12.4 ± 4.9; non-ambulatory = 19.0 ± 9.7; controls = 10.1 ± 0.8) revealing ventilatory and mechanical inefficiency. Despite strong correlation between VO2 peak and 6MWD, severity of impairment was discordant. Conclusion: Valid CPET is feasible in DMD, revealing low VO2 peak due to abnormal muscle metabolic and cardiorespiratory responses during dynamic exercise. CPET reveals cardiorespiratory limitations in DMD boys with unremarkable 6MWD, and should be considered an integrative approach in clinical care and assessment of emerging therapeutics.