Introduction: Duchenne muscular dystrophy (DMD) is fatal X-linked neuromuscular disorder characterized by progressive dilated cardiomyopathy, respiratory insufficiency, and autonomic dysfunction. Cardiac, pulmonary, and autonomic function are thought to decline with disease progression in a co-dependent manner. However, these relationships have not been systematically evaluated. Right ventricular health, which depends on normal pulmonary hemodynamics, also remains understudied in DMD. The objective of this study was to characterize the relationships of pulmonary function test (PFT) parameters and indices of autonomic function, with cardiac magnetic resonance imaging (CMR) biomarkers of biventricular function and remodeling in children and adolescents with DMD.

Methods: We performed a prospective analysis of 27 boys with DMD who underwent CMR, PFT, and 24-hour ambulatory electrocardiogram (aECG) monitoring at two children’s hospitals to evaluate cardiac, pulmonary, and autonomic function, respectively. The CMR protocol included conventional biventricular volumetric and functional assessment, late gadolinium enhancement (LGE) imaging to detect focal myocardial fibrosis, and T1 mapping to assess diffuse fibrosis. PFTs were performed per institutional protocols and included spirometry and respiratory muscle strength testing. Average heart rate and the standard deviation of the time between normal heartbeats (SDNN) were obtained from aECG. The cohort was stratified based on presence of LGE and predicted forced vital capacity (FVC) <80%, both suggestive of more advanced disease.

Results: Median age of the cohort was 13 years (IQR 11-15.5 years). 8 patients were LGE (+) and 19 were LGE (-). LGE (+) boys had significantly lower percent predicted maximum expiratory pressure (MEP%) (25.8 vs. 48.0, p=0.035). Other respiratory, autonomic, and right ventricular function indices did not correlate with LGE status. There were no significant differences in CMR or autonomic parameters between boys with normal (FVC ≥80%) and abnormal (FVC <80%) pulmonary function.

Conclusion: Our findings suggest that cardiac, pulmonary, and autonomic function may decline independently with disease progression; dysfunction in one system did not necessarily correlate with dysfunction in the other. Decline in respiratory muscle strength, as measured by MEP%, was seen more often in patients with myocardial scarring (indicative of more advanced disease). Further longitudinal investigation involving prospective modulation of respiratory support during CMR may elucidate more subtle cardiopulmonary-autonomic interactions in DMD.