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Original Investigation
February 2017

Myocardial Fibrosis Progression in Duchenne and Becker Muscular DystrophyA Randomized Clinical Trial

Author Affiliations
  • 1Heart Institute, InCor, University of São Paulo Medical School, São Paulo, Brazil
  • 2Axial Medicina Diagnóstica Belo Horizonte, Minas Gerais, Brazil
  • 3Department of Pediatrics, Federal University of Minas Gerais Medical School, Belo Horizonte, Minas Gerais, Brazil
  • 4Human Genome and Stem-Cell Center, Biosciences Institute, University of São Paulo, São Paulo, Brazil
JAMA Cardiol. 2017;2(2):190-199. doi:10.1001/jamacardio.2016.4801
Key Points

Question  Does early use of angiotensin-converting enzyme inhibitor therapy in patients with Duchenne or Becker muscular dystrophy who have preserved left ventricular ejection fraction affect the progression of myocardial fibrosis defined as percentage of left ventricular mass identified by cardiovascular magnetic resonance?

Findings  In this randomized clinical trial of 42 patients with myocardial fibrosis and preserved left ventricular ejection fraction, those receiving angiotensin-converting enzyme inhibitors demonstrated significantly lower myocardial fibrosis progression compared with those who were untreated. Early use of angiotensin-converting enzyme inhibitor therapy was independently associated with a lower rate of myocardial fibrosis progression.

Meaning  Early angiotensin-converting enzyme inhibitor therapy, initiated when myocardial fibrosis is identified before a decrease in left ventricular ejection fraction, seems to benefit patients with Duchenne or Becker muscular dystrophy.

Abstract

Importance  In Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), interventions reducing the progression of myocardial disease could affect survival.

Objective  To assess the effect of early angiotensin-converting enzyme (ACE) inhibitor therapy in patients with normal left ventricular function on the progression of myocardial fibrosis (MF) identified on cardiovascular magnetic resonance (CMR).

Design, Setting, and Participants  A randomized clinical trial conducted in 2 centers included 76 male patients with DMD or BMD undergoing 2 CMR studies with a 2-year interval for ventricular function and MF assessment. In a non–intent-to-treat trial, 42 patients with MF and normal left ventricular ejection fraction (LVEF) were randomized (1:1) to receive or not receive ACE inhibitor therapy. The study was conducted from June 26, 2009, to June 30, 2012. Data analysis was performed from June 30, 2013, to October 3, 2016.

Interventions  Randomization (1:1) to receive or not receive ACE inhibitor therapy.

Main Outcomes and Measures  Primary outcome was MF progression from baseline to the 2-year CMR study.

Results  Of the 76 male patients included in the study, 70 had DMD (92%) and 6 had BMD (8%); mean (SD) age at baseline was 13.1 (4.4) years. Myocardial fibrosis was present in 55 patients (72%) and LV systolic dysfunction was identified in 13 patients (24%). Myocardial fibrosis at baseline was an independent indicator of lower LVEF at follow-up (coefficient [SE], −0.16 [0.07]; P = .03). Among patients with MF and preserved LVEF (42 [55%]), those randomized (21 patients in each arm) to receive ACE inhibitors demonstrated slower MF progression compared with the untreated group (mean [SD] increase of 3.1% [7.4%] vs 10.0% [6.2%] as a percentage of LV mass; P = .001). In multivariate analysis, ACE inhibitor therapy was an independent indicator of decreased MF progression (coefficient [SE], −4.51 [2.11]; P = .04). Patients with MF noted on CMR had a higher probability of cardiovascular events (event rate, 10 of 55 [18.2%] vs 0 of 21 [0%]; log-rank P = .04).

Conclusions and Relevance  In this 2-year, follow-up, randomized clinical trial of patients with Duchenne or Becker muscular dystrophy whose LVEF was preserved and MF was present as determined on CMR, ACE inhibitor therapy was associated with significantly slower progression of MF. The presence of MF was associated with worse patient prognosis.

Trial Registration  clinicaltrials.org Identifier: NCT02432885

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