Natural History of Cardiomyopathy in Duchenne Muscular Dystrophy and the Effects of Angiotensin-Converting Enzyme Inhibitor with or without -Blocker (S15.003)

Abstract

Objective: To prospectively examine the natural history of cardiomyopathy (CM) in Duchenne muscular dystrophy (DMD) patients & assess responses to treatment utilizing angiotensin-converting enzyme inhibitors (ACEI) with or without concomitant β-blocker (BB). Background Cardiomyopathy is an invariable consequence of DMD. Suggested treatments include ACEI and/or BB, but few large series are reported. We present 65 DMD patients with CM treated with ACEI or ACEI+BB, including their natural history & therapeutic responses. Design/Methods: Serial echocardiograms were performed and reported for natural history analysis prior to initiation of therapy when available. Adequate ejection fractions (EF) were obtained in 45 patients at initiation of therapy (EF 100 beats/min. Data analyzed using paired t-test & linear regression. Results: Natural history data (n=24) demonstrated decreased EF over time (r2=0.22). At ACEI therapy initiation, the mean age was 14.7 ± 4.4 years & mean EF was 44.3 ± 8.3%. BB therapy was used in 25/45 patients. Mean age for ACEI+BB group was 16.1 ± 3.9 years. Both groups demonstrated significant improvement compared to natural history (p≤0.0001 for ACEI, p Conclusions: Patients with DMD demonstrated gradual decline in myocardial function. Treatment with ACEI or ACEI+BB resulted in significant improvement compared to the natural history. No significant difference was noted in EF improvement between treatment groups. Treatment with ACEI or ACEI+BB can delay progression of CM. Supported by: Data collection was made possible by the Muscular Dystrophy Association & Wellstone Muscular Dystrophy Cooperative Research Center (NIH sponsored) and led to creation of the MDA DMD Clinical Network. Mutational analysis for most patients performed as part of the United Dystrophinopathy Project-supported by NINDS (R01 NS043264)[K.M.F.]. Disclosure: Dr. Thrush has nothing to disclose. Dr. Viollet has nothing to disclose. Dr. Flanigan has received personal compensaiton for activities with AVI Therapeutics, Prosensa Therapeutics, and PTC, Inc. Dr. Flanigan has received research support from PTC Therapeutics. Dr. Mendell has received research support from AVI BioPharmaceuticals Inc. Dr. Allen has nothing to disclose.