P.2.16 Cooperative International Neuromuscular Research Group (CINRG) study of echocardiographic outcome measures for use in clinical trials in muscular dystrophy

Cardiomyopathy is a significant clinical outcome for muscular dystrophy. Echocardiography (echo) is a versatile measure of cardiac function that is available in most muscular dystrophy centers and, therefore, has high utility for clinical care and multicenter clinical trials. Echo outcomes for treatment trials in muscular dystrophy have traditionally measured ejection fraction (EF). However, this measure can be challenging to obtain with more advanced disease due to chest wall deformities and difficulty with positioning for testing. This study was performed to pilot prospective measures of echo outcomes at 5 centers of the Cooperative International Neuromuscular Research Group (CINRG) using a central sonography protocol and 2 central readers. Forty-eight participants 8–18 years old with genetically confirmed Duchenne muscular dystrophy, Becker muscular dystrophy or limb girdle muscular dystrophy underwent electrocardiogram, echo and B-type natriuretic peptide testing. Notably, the echo quality was insufficient to read EF for 23 studies by one reader and for 5 studies by the other reader. In contrast, myocardial performance index (MPI) measured by Doppler could be read by both readers in 46 studies. Furthermore, the agreement of cardiac measures between the 2 independent readers and between one reader performing 2 different reads was greater for MPI than for EF. In 35% of studies, an abnormal MPI while EF remained normal suggested early cardiac dysfunction. This finding suggests that MPI may demonstrate increased sensitivity to detect cardiomyopathy when compared to EF. In subsequent analyses to explore echo measures of even greater sensitivity to detect cardiac dysfunction, speckle tracking was performed to measure longitudinal and circumferential strain. The results suggest that MPI and strain measures are sensitive and amenable to central reading for muscular dystrophy clinical trials.