Abstract 2156: Idebenone Improves Peak Systolic Strain in Children With Duchenne Muscular Dystrophy With Preserved Ejection Fraction: Results of a 12 Month Double-blind, Randomized, Controlled Trial
Objective - To evaluate effect of treatment with idebenone compared to placebo on myocardial radial and longitudinal deformation parameters in children and adolescents with Duchenne muscular dystrophy (DMD).
Background - Idebenone supports mitochondrial respiratory chain function and reduces oxidative stress. We have shown that early long-term treatment with idebenone is cardioprotective and improves exercise performance in the dystrophin-deficient mdx mouse. Peak systolic strain is reduced in young patients with DMD and precedes overt cardiac dysfunction. We hypothesized that early treatment with idebenone in presymptomatic children has a cardioprotective effect.
Design/Methods - 21 DMD patients (8 –16 yr) without overt cardiac dysfunction but reduced baseline peak radial systolic strain values were enrolled in a phase II double-blind, randomized, placebo-controlled trial. Comedication with glucocorticoids was allowed at stable dosage; use of ACE-inhibitors was excluded. Thirteen patients received idebenone (450 mg daily) and 8 patients placebo for 52 weeks. The primary endpoint was the change from baseline in peak systolic radial strain of the left ventricular (LV) inferolateral wall, the region of the heart which is most affected in DMD.
Results - All subjects completed the study, and idebenone showed good safety and tolerability. Compared to placebo, treated patients showed significant improvement in peak systolic radial strain of the LV inferolateral wall (percent change 28.9 ± 40.7 placebo and 104.4 ± 92.2 idebenone; p= 0.030). Peak systolic longitudinal strain of the LV lateral wall improved in patients on idebenone and deteriorated in patients on placebo (percent change 42.3 ± 61.8 idebenone −4.5 ± 23.0 placebo; p=0.039). Ejection fraction was normal at baseline and did not significantly change in both groups.
Conclusions - Idebenone improves cardiac radial and longitudinal deformation parameters in the inferolateral wall in children with DMD which have not yet developed overt cardiac dysfunction. The results provide the basis and guidance for phase III studies with SNT-MC17/idebenone in DMD. This is the first clinical trial where strain imaging was used as a primary endpoint in children.