Abstract 17250: Serum vs. Imaging Biomarkers of Myocardial Injury in Duchenne Muscular Dystrophy: Findings from the E-SCAR DMD Trial

Abstract

Introduction: Cardiomyopathy has become a leading cause of death in Duchenne muscular dystrophy (DMD). We previously showed that early mineralocorticoid receptor antagonist therapy reduces myocardial damage in a preclinical model of DMD. The Eplerenone for Subclinical Cardiomyopathy in DMD (E-SCAR DMD, NCT01521546) is a multicenter randomized placebo-controlled clinical trial evaluating eplerenone in boys with preserved left ventricular ejection fraction (LVEF) and evident myocardial injury by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Hypothesis: To better define biomarkers of early disease, we hypothesized that LGE has greater sensitivity vs. serum biomarkers for myocardial injury in DMD cardiomyopathy. Methods: Boys with DMD age ≥ 7 years were enrolled across 3 centers. LGE-CMR images were acquired using comparable techniques across 3T scanners, and core laboratory LGE quantification was performed blinded to laboratory findings as a percentage of LV mass using software based on the full-width half-maximum technique. Troponin-I, creatine kinase (CK) and CK isoenzymes were measured from blood samples obtained at the time of CMR examination using standardized clinical assays. Results: 42 boys age 16 ± 7 years had preserved LVEF (57 ± 6%), and LGE-positive regions averaged 5.0 ± 2.6% of LV myocardium. While 100% had evident myocardial injury by LGE, 43% had measurable CK-MB and only 18% had detectable troponin-I in serum (Figure). %LGE was higher (5.4 ± 2.7 vs. 3.3 ± 1.8%, p<0.05) and LVEF was lower (55.4 ± 4.9 vs. 59.0 ± 7.1%, p < 0.01) in boys with detectable vs. those with undetectable troponin-I, whereas detectable CK-MB did not predict higher %LGE or lower LVEF. Conclusion: DMD patients with abnormal myocardium by LGE-CMR may have no detectable abnormalities by serum biomarkers, underscoring the importance of myocardial injury imaging in identifying patients with subclinical cardiomyopathy who may benefit from early treatment.