Abstract 14062: Longitudinal Rate of Change for Cardiac Magnetic Resonance Biomarkers Associates With Mortality in Duchenne Muscular Dystrophy

Abstract

Introduction: Cardiomyopathy (CM) is the leading cause of death in Duchenne muscular dystrophy (DMD). Progression is variable. Multiple DMD-specific CM medications are in development, but there are no established outcome measures for therapeutic trials. Our prior work demonstrated an association between cardiac magnetic resonance (CMR) metrics and mortality, including left ventricular ejection fraction (LVEF), ventricular volumes, and native T1 mapping. The objective of this study was to determine whether longitudinal change in these metrics associates with all-cause mortality. Methods: Seventy-eight DMD subjects underwent 211 comprehensive CMR studies, including LVEF, indexed LV end diastolic and systolic volumes (LVESVi and LVEDVi), and native T1 mapping. To explore how the slope of CMR biomarkers affects mortality, multivariable linear regression was used to model age, mortality, and the interaction term of age and mortality on predictors of interest (LVEF, LVEDVi, LVESVi, native T1). Results: At baseline CMR, the median age was 12.5 years (range 7.4-27.5), and the median LVEF was 57%; 32 subjects (41%) had LVEF < 55%. LGE was present in 54 subjects (71%). Fifteen subjects (19%) died over a median follow up of 5 years (IQR 3.1,7). The slope of LVEF decline differentiated between subjects with and without mortality (p<0.001) ( Figure 1 ). A steeper increase in LVEDVi and LVESVi also associated with mortality (p<0.001), while change in native T1 did not. Conclusions: DMD all-cause mortality is associated with the slope of progression of LVEF and ventricular volumes. Aggressive medical therapy to decrease the rate of progression may improve mortality in this patient population. In addition, a decrease in the rate of progression may serve as a valid surrogate outcome measure for therapeutic trials.