“Dilated cardiomyopathy is a major complication and leading cause of death in Becker muscular dystrophy (BMD). Echocardiographic measures such as left ventricular ejection fraction (LVEF%) and left ventricular end-diastolic volume indicized by body surface (LVEDVi) are routinely used for clinical monitoring of patients, but their rate of change over time has not been quantified in natural history studies.We present longitudinal echocardiographic data from 92 male BMD patients (average age±SD: 32.7±16.4years, range 4-70), followed up over 4.5±3.8 years (maximum 16.8) with 4.3±2.8 echocardiograms (maximum 12). Linear mixed models were used to estimate yearly change of measures and correlations with mutation type.The estimate of LVEF reduction was -0.14%±0.05% (standard error, SE) per year (p=0.008), while LVEDVi was more variable and did not decrease significantly over time in the overall cohort. A negative effect on LVEF was observed for N-terminal mutations (involving the first 10 exons of the coding DMD sequence), estimated at -15.6 ± 3.5%, p = 0.00003. regarding LVEDVi, a negative effect (larger volume) was observed for both N-terminal mutations (+36.3 ± 8.5 mL/m2, p=0.00008), but also duplications (+31.5 ± 11.8 mL/m2, p = 0.010) and nonsense mutations (+35.6 ± 13.7 mL/m2, p=0.012).
In conclusion, LVEF decreases slowly but significantly over time in BMD, some mutational groups (e.g. N-terminal) showing faster and more frequent progression of hypokinetic cardiomyopathy. LV dilation is less frequent and more variable, affecting some mutational groups more prominently (e.g. N-terminal, nonsense, duplications). Limitations of this retrospective study include a yet incomplete evaluation of the efficacy of cardiological treatments.”