Abstract 4141603: Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases as Biomarkers in Duchenne Muscular Dystrophy Cardiomyopathy

Introduction/Background: Cardiomyopathy is the leading cause of death in patients with Duchenne muscular dystrophy (DMD), but existing biomarkers are poor indicators of cardiomyopathy onset and progression. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate collagen turnover and have previously been associated with DMD cardiomyopathy through their role in fibrosis. Hypothesis: We hypothesized that MMPs/TIMPs would correlate with cardiac magnetic resonance (CMR) measures of cardiomyopathy. Aims: We aimed to assess the relationship between circulating MMPs/TIMPs and CMR measures of cardiomyopathy. Methods: Patients with DMD were prospectively enrolled in a multi-center observational study with CMR, quantitative muscle testing (QMT), and bloodwork. CMR included measurement of left ventricular ejection fraction (LVEF), late gadolinium enhancement (LGE) global severity score (GSS), LGE using full-width half-maximum (FWHM), and global circumferential strain (Ecc) using tagged images. Spearman’s rank test was used to assess correlation between CMR measurements and MMPs. Wilcoxon rank-sum tests were used to compare MMPs by binary categories. Results: A total of 166 patients were included (mean age 14.4 years, 83% white/11.9% Black/10.8% Hispanic). MMP1 and the MMP1/TIMP1 ratio correlated negatively with LVEF and positively LGE GSS (Table 1). MMP7 correlated positively with LGE GSS and Ecc. Patients with LGE had higher MMP1, MMP7, and MMP1/TIMP1 (Figure 1). Similarly, patients with reduced LVEF had higher MMP1 and MMP1/TIMP1, although not MMP7. MMP7 and MMP1/TIMP1 were also negatively correlated with total QMT. Conclusions: Multiple MMPs and TIMPs associate with DMD cardiomyopathy severity and may serve as biomarkers of DMD cardiac disease progression.