Abstract 4366789: Natural History Nomograms of Duchenne Cardiomyopathy by Cardiac Magnetic Resonance Imaging

Abstract

Introduction: Duchenne Muscular Dystrophy (DMD), an X-linked disorder resulting in skeletal and cardiac myopathy, typically leads to death from 20-40 years of age. Cardiac magnetic resonance (CMR) imaging is the gold standard for assessment of cardiac progression. However, it can be difficult for a clinical to understand the significant of trends in measurements and how they should alter management. While normal reference ranges for volumes and function are available in children and adults, it is not disease specific and may not be as useful in DMD disease progression. Research Questions: We hypothesized that a predictive model detailing the usual progression of disease could be developed from the DMD Cardiac Care Consortium Natural History Study (DMDCCC NHS) data. Methods: The DMDCCC NHS consists of 183 patients enrolled from 7 sites around the country with serial CMR imaging at baseline, 1 year, and 2 years. The CMR images are analyzed by a single reader at a central core laboratory. Analysis includes left ventricular ejection fraction (LVEF), indexed left ventricular end diastolic and systolic volumes (LVEDVi and LVESVi), and circumferential myocardial strain. Quantile longitudinal regression modeling with restricted cubic splines was used to evaluate the median, 5th, 25th, 75th, and 95th percentiles at each LVEF, LVEDVi, and LVESVi for age. Results: The median age at baseline CMR was 12.5 years (Inerquartile range (IQR) 10-16). The median LVEF at baseline was 57% (IQR 52-61). Of 183 patients, 74% had evidence of LGE and 34% had an LVEF <55% at baseline. There were a total of 383 CMR studies included in the analysis. As expected, LVEF, LVEDVi, and LVESVi curves demonstrate higher LVEF and lower LVEDVi and LVESVi at younger ages, followed by a more progressive decline with a plateau at older ages (Figure 1). Conclusion: There are predictable changes in LVEF and LV volumes in the DMD population based on age at CMR, which may help guide therapy and prognostic expectations particularly in patients who are progressing outside the percentiles. We hypothesize that the early improvement in function may be secondary to improved image quality with age and that the plateau effect in young adulthood is likely secondary to mortality in those with more severe cardiac disease. Despite these limitations, the data can aid clinicians in understanding the severity of disease.