Early-onset Late Gadolinium Enhancement Is a Prognostic Factor for Cardiomyopathy Young Patients with Duchenne Muscular Dystrophy

Background: Dilated cardiomyopathy (DCM) is an inevitable complication of Duchenne muscular dystrophy (DMD). Detecting the earliest changes of this disease may help us understand the impact of treatments. Late gadolinium enhancement (LGE) demonstrated by cardiac MRI is known to occur in DMD-related DCM and indicates myocyte death and replacement by fibrofatty tissue.

Methods: We conducted a retrospective chart review to identify patients with DMD in our center seen between January 2009 and July 2013. Subjects were divided by presence of LGE before age of 14. We excluded patients without MRI data, or with a first MRI after age 14 demonstrating LGE (as it could not be determined which group they belong to). We also reviewed accompanying clinical data including echocardiograms and genetic mutations. Normal left ventricular (LV) function is defined by a fractional shortening greater than 28%, and tonic contraction of the LV is defined as an LV internal dimension in diastole (LVIDd) more than 1.5 SD below age and size related mean. Statistical analyses included student’s T-test, chi-squared analysis, polynomial regression, as well as descriptive statistics.

Results: Forty-three subjects met inclusion criteria. Two were excluded due to inadequate MRI quality (n=1) or lack of gadolinium contrast (n=1). Of the remaining 41 subjects, those with LGE demonstrated before age 14 (n= 15) exhibited a more rapid decline in LV fractional shortening (Figure 1), onset of LV tonic contraction in the first decade (Figure 2), and LV dilation in adolescence compared to those without LGE before age 14 (n= 26). There was no difference in age at initiation of ACE inhibition (p=0.18) or mineralocorticoid receptor antagonist (p= 0.74) between the two groups. Early-onset LGE was not associated with obesity (chi-squared =0) or age at loss of ambulation (p=0.74). Of the patients with presence of LGE before age 14, 8 had exon deletions (53%), 6 had point mutations (40%), and 1 had exon duplication (7%). Of the patients without LGE before age 14, 15 had exon deletions (58%), 8 had point mutations (31%), and genetic reports were unavailable in 3 patients (n=11%, 2 had diagnosis proven by skeletal muscle biopsy).

Conclusion: Early onset of cardiac myocardial fibrosis as indicated by LGE on cardiac MRI is associated with earlier progression of cardiomyopathic changes including LV systolic dysfunction and a biphasic response of LV dimension. In this limited cohort, other clinical factors such as obesity, early loss of ambulation, or specific genetic mutations do not clearly correlate with earlier DCM onset. This provides guidance regarding the application of cardiac MRI in young patients with pre-clinical DCM.