title: Myocardial Fibrosis Progression in Duchenne and Becker Muscular Dystrophy: A Randomized Clinical Trial.
abstract: In Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), interventions reducing the progression of myocardial disease could affect survival.
  
  
  
  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).
  
  
  
  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.
  
  
  
  Randomization (1:1) to receive or not receive ACE inhibitor therapy.
  
  
  
  Primary outcome was MF progression from baseline to the 2-year CMR study.
  
  
  
  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).
  
  
  
  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.
  
  
  
  clinicaltrials.org Identifier: NCT02432885.
authors.affiliation: Heart Institute, InCor, University of São Paulo Medical School, São Paulo, Brazil2Axial Medicina Diagnóstica Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Marly Conceição
authors.initials: MC
authors.lastname: Silva
authors.affiliation: Heart Institute, InCor, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Tiago Augusto
authors.initials: TA
authors.lastname: Magalhães
authors.affiliation: Department of Pediatrics, Federal University of Minas Gerais Medical School, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Zilda Maria Alves
authors.initials: ZM
authors.lastname: Meira
authors.affiliation: Heart Institute, InCor, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Carlos Henrique Reis Esselin
authors.initials: CH
authors.lastname: Rassi
authors.affiliation: Department of Pediatrics, Federal University of Minas Gerais Medical School, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Amanda Cristina de Souza
authors.initials: AC
authors.lastname: Andrade
authors.affiliation: Heart Institute, InCor, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Paulo Sampaio
authors.initials: PS
authors.lastname: Gutierrez
authors.affiliation: Heart Institute, InCor, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Clerio Francisco
authors.initials: CF
authors.lastname: Azevedo
authors.affiliation: Department of Pediatrics, Federal University of Minas Gerais Medical School, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Gurgel-Giannetti
authors.affiliation: Human Genome and Stem-Cell Center, Biosciences Institute, University of São Paulo, São Paulo, Brazil.
authors.forename: Mariz
authors.initials: M
authors.lastname: Vainzof
authors.affiliation: Human Genome and Stem-Cell Center, Biosciences Institute, University of São Paulo, São Paulo, Brazil.
authors.forename: Mayana
authors.initials: M
authors.lastname: Zatz
authors.affiliation: Heart Institute, InCor, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Kalil-Filho
authors.affiliation: Heart Institute, InCor, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Rochitte
mesh_terms: D000293:Adolescent; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001706:Biopsy; D009202:Cardiomyopathies / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D002648:Child; D018450:Disease Progression; D005260:Female; D005355:Fibrosis / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D005500:Follow-Up Studies; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000150:complications* / Q000175:diagnosis; D009206:Myocardium / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D012042:Registries; D013318:Stroke Volume / Q000502:physiology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors