Irwin B. Jacobs

Progressive left ventricular dysfunction and long-term outcomes in patients with Duchenne muscular dystrophy receiving cardiopulmonary therapies

Objective To describe the natural history of cardiomyopathy in patients with Duchenne muscular dystrophy (DMD) who are receiving contemporary therapies. Methods This is a single-institution retrospective cohort study of 57 patients aged >15 years with DMD. Serial digital echocardiograms were performed over a median follow-up of 8 years. Left ventricular dysfunction (LVD) was defined as shortening fraction (SF) <29% plus focal wall motion abnormalities. Therapies included ACE inhibitors, beta-blockers and assisted ventilation. Results The SF declined progressively in 53/57 patients (93%). LVD occurred in 40 of 57 patients (70%), with variable age at onset (median 18 years, IQR 14–21.5 years). Rate of SF decline (–1.51%±1.16%/year) was variable and unrelated to genotype. However, survival was shorter for patients with LVD onset at age <18 years vs onset at ≥18 years (death at 21.1±2.5 years vs 33.1±4.4 years; P<0.001). Death occurred in 27/57 (47%) patients at a median age of 26.3 years (IQR 20.6–31.5). Death was preceded by LVD in 22/27 patients (81%), 15 (68%) of whom developed class 4 heart failure (CHF). Time from CHF to death was brief (median 8.0 months). Conclusion Despite contemporary therapies, SF declined progressively in almost all patients. Age at onset of LVD and age at death were variable and unrelated to genotype; however, survival was shortened for patients with LVD onset at age <18 years. Death was usually preceded by LVD. CHF was a sentinel event, with death occurring shortly thereafter.