The Subclinical Window for Cardioprotection in Duchenne Muscular Dystrophy: A Systematic Review and Meta-analysis

Cardiomyopathy is a major cause of morbidity and mortality in Duchenne muscular dystrophy (DMD). Myocardial injury begins during a prolonged subclinical phase while left ventricular ejection fraction (LVEF) remains preserved, suggesting a potential therapeutic window for early cardioprotective intervention. This study evaluated whether cardioprotective pharmacotherapy initiated before overt ventricular dysfunction is associated with improved clinical outcomes in DMD. A systematic review and meta-analysis were conducted following PRISMA guidelines (PROSPERO: CRD420261353435). Randomized trials and observational studies evaluating early cardioprotective therapy were included. Effect estimates were pooled using random-effects models to account for between-study heterogeneity. Fourteen studies including 1,788 patients were included in the review. Early cardioprotective therapy was associated with a significantly reduced risk of death (HR 0.39, 95% CI 0.23–0.65; I 2 = 0%; K = 3, N = 958), as well as a lower risk of clinically meaningful cardiac progression (HR 0.36, 95% CI 0.21–0.62; I 2 = 21.5%) and progression to overt left ventricular dysfunction (HR 0.41, 95% CI 0.24–0.70; I 2 = 12.0%). In contrast, early therapy was not associated with a significant change in short-term left ventricular ejection fraction (mean difference −0.14%, 95% CI −2.57 to 2.29; I 2 = 0%). Early cardioprotective therapy initiated prior to overt ventricular dysfunction is associated with lower mortality and reduced progression of cardiomyopathy in Duchenne muscular dystrophy. These findings support the early initiation of cardioprotective therapy during the subclinical phase of Duchenne cardiomyopathy.