Duchenne Muscular Dystrophy Patients: Troponin Leak in Asymptomatic and Implications for Drug Toxicity Studies

BACKGROUND: Cardiomyopathy is the leading cause of death in Duchenne Muscular Dystrophy (DMD), but studies suggest heart failure biomarkers correlate poorly with cardiomyopathy severity. DMD clinical trials have used troponin I (cTnI) as a biomarker of toxicity but it is unclear if asymptomatic DMD patients have elevated cTnI. We longitudinally evaluated cTnI, brain natriuretic peptide (BNP), and N-terminal proBNP (NT-proBNP) in a DMD cohort. METHODS: DMD patients were prospectively enrolled and followed for three years. Serum was drawn at time of cardiac magnetic resonance (CMR). Normal biomarker values were derived from healthy subjects. Biomarkers were correlated with CMR markers. RESULTS: All subjects were asymptomatic at time of enrollment. Several DMD subjects had transiently elevated cTnI. Those with elevated cTnI were more likely to have late gadolinium enhancement on baseline CMR. NT-proBNP correlated with indexed left ventricular end diastolic and maximum left atrial volumes. Otherwise, standard cardiac biomarkers did not correlate with CMR markers of cardiomyopathy. CONCLUSIONS: CTnI, BNP, and NT-proBNP do not correlate with CMR assessment of cardiomyopathy progression. A subset of DMD patients have asymptomatic cTnI leak of uncertain clinical significance, though of critical importance if cTnI is used to assess for cardiac toxicity in future drug trials.