Background: Dilated cardiomyopathy (DCM) is an inevitable complication of Duchenne muscular dystrophy (DMD). Late gadolinium enhancement (LGE) demonstrated by cardiac MRI (cMRI) is known to occur in DMD cardiomyopathy and indicates myocyte death and replacement by fibrofatty tissue. In these patients, LGE increases with age and correlates closely with progression of left ventricular (LV) dilation and dysfunction. While the presence of LGE tends to increase over time, the development and implication of early-onset LGE (before adolescence) has not been well-characterized.

Methods: We conducted a retrospective chart review to identify all patients with DMD in our center seen between January 2009 to July 2013. Subjects were cohorted by presence of LGE before the age of 14. We excluded patients in whom we could not determine LGE status prior to age 14. Primary outcome was decline in ventricular function as assessed by fractional shortening (FS) on echocardiogram. Normal LV systolic function was defined as FS greater than 28%. Charts were reviewed for patient demographics, confirmation of diagnosis, genetic testing, clinical status, and echocardiographic and cMRI information.

Results : Forty-three subjects were evaluated. Two were excluded due to inadequate MRI quality (n=1) or lack of gadolinium contrast (n=1). Of the remaining 41 subjects, 15 demonstrated LGE before age 14 (“early LGE”), and 26 had no LGE by age 14 (“controls”). Patients with early LGE had earlier average age at initiation of ACE inhibition (p=0.025), mineralocorticoid receptor antagonism (p= 0.0024), and beta blockade (p=0.0017), suggesting aggressive clinical management in response to early abnormal MRI findings. Those with early LGE exhibited a more rapid decline in LV fractional shortening compared with controls (p=0.028) but did not demonstrate significant difference in LV chamber dilation (p=0.1547). Early LGE was not associated with obesity (p=0.32) or age at loss of ambulation (p=0.31). Of the patients with early LGE, 8 had exon deletions (53%), 6 had point mutations (40%), and 1 had exon duplication (7%). Of the control patients, 15 had exon deletions (58%), 8 had point mutations (31%), and genetic reports were unavailable in 3 patients (11%, n= 2 had diagnosis proven by skeletal muscle biopsy).

Conclusion: LGE occurs before age 14 in approximately one-third of Duchenne patients. Early onset of myocardial fibrosis as indicated by LGE on cardiac MRI, even if concurrent systolic function and cardiac dimensions measured by echocardiogram appear normal, is associated with earlier progression to LV systolic dysfunction. Specifically in this study, genetic etiology and severity of skeletal muscle weakness did not correlate with earlier progression of cardiomyopathy. The authors advocate for obtaining at least one MRI in DMD patients prior to age 14 to risk stratify patients and personalize medication therapy.