Central Arterial Wave Reflection in Duchenne Muscular Dystrophy: Role of Ambulation and Corticosteroid Treatment

• Grant Maxa, Human Physiology, University of Delaware

• Melissa Witman, Kinesiology and Applied Physiology, University of Delaware

Duchenne muscular dystrophy (DMD) is a genetic disorder marked by dystrophin deficiency, resulting in progressive muscle wasting and loss of ambulation. Systemic corticosteroids are the standard of care, which have improved non-cardiac outcomes, e.g., skeletal muscle function; however, dilated cardiomyopathy remains the leading cause of death. Peripheral arterial dysfunction precedes cardiovascular disease (CVD), and while non-invasive markers of arterial wave reflection like augmentation index (AIx) and reflection magnitude (RM) are elevated in DMD, the role of ambulation or corticosteroid use remains unclear. PURPOSE: To examine the effects of ambulation status and corticosteroid treatment duration on arterial wave reflection in boys diagnosed with DMD. METHODS: Peripheral pressure waveforms were recorded in boys with DMD and typically-developing controls using an oscillometric cuff device. Central pressure waveforms were derived via a generalized transfer function, and AIx and RM recorded. Ambulation was defined as the ability to walk independently outdoors for short distances, as per the DMD Functional Ability Self-Assessment Tool. Corticosteroid duration was calculated in years since first dose and dichotomized by median split into short (<6 years) and long (≥6 years) treatment duration groups. Multivariable linear regression was used to compare AIx and RM between DMD and control groups, adjusting for height, heart rate, body mass index (BMI), and central mean arterial pressure. RESULTS: Boys with DMD had higher AIx (p<0.001) and RM (p <0.001) than controls. Non-ambulatory boys with DMD had higher AIx (p=0.007) and RM (p=0.007) than ambulatory counterparts. Those with long corticosteroid treatment duration had lower RM (p=0.048), and a non-significant trend toward lower AIx (p=0.097). CONCLUSION: DMD is associated with elevated arterial wave reflection. Impaired ambulation and shorter duration of steroid treatment may negatively affect these parameters. Larger scale longitudinal studies are warranted into therapies that enhance peripheral circulation, which may offer cardiovascular benefits for patients with DMD with reduced mobility, and the long-term vascular consequences of varying types of corticosteroid treatment.