Cardiopulmonary Exercise Testing Sheds Light on Early Physiologic Decline in Duchenne Muscular Dystrophy

While functional assessments such as the six-minute walk test (6MWT) remain the standard for tracking disease progression in Duchenne muscular dystrophy (DMD), they may not fully capture early physiologic impairment. A new prospective study published in the Journal of Neurology demonstrates how cardiopulmonary exercise testing (CPET) can provide a more granular picture of evolving cardio-respiratory and metabolic limitations—even in ambulatory patients with preserved motor function.

The study enrolled 39 male patients aged 7-16 with genetically confirmed DMD across a U.S. academic center. All were on stable corticosteroids and ambulatory at baseline, with North Star Ambulatory Assessment (NSAA) scores ≥26 (mean: 31.2). Participants underwent cycle ergometer CPET alongside standard 6MWT evaluations and pulmonary function testing.

The key objectives of the study were to evaluate the safety, feasibility, and physiological insights offered by CPET, with a focus on ventilatory, cardiac, and metabolic performance indices.

Subclinical Impairment Despite Preserved Ambulation

The researchers found:

• CPET was safe and well-tolerated across all subjects, even among those under 10 years old.
• Average peak oxygen uptake (VO₂peak) was 27.5 mL/kg/min—below age-adjusted norms, despite normal 6MWT results in many patients.
• Ventilatory efficiency (VE/VCO₂) was elevated in 48.7% of patients, indicating early ventilatory inefficiency not captured by resting spirometry.
• Chronotropic insufficiency (blunted heart rate response) was noted in over one-third of patients, independent of steroid use.
• Despite NSAA scores >30 in most participants, metabolic thresholds were crossed at low workloads, suggesting reduced aerobic capacity.

Importantly, VO₂peak and VE/VCO₂ correlated poorly with 6MWT distance and NSAA scores, suggesting CPET uncovers a distinct dimension of physiologic burden that may precede observable declines in gross motor performance.

Given these findings, CPET may be able to:

• Identify patients at risk for impending decline before clinical milestones are lost, potentially allowing earlier initiation of cardiac or pulmonary therapies.
• Inform individualized exercise prescriptions or aerobic conditioning programs, addressing deconditioning without overexertion.
• Serve as a complementary biomarker of treatment response—particularly in early or stable-phase patients where gross motor scores plateau—as emerging DMD therapies aim to stabilize or improve function.

Reference:

Bomma RS, Li H, Jackson E, et al. Cardiopulmonary exercise testing as an integrative approach to explore physiological limitations in Duchenne muscular dystrophy. J Neurol. Published online 2025. doi:10.1007/s00415-025-12347-6.