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

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.