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?
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.
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.
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).
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.
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.
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.
clinicaltrials.org Identifier: NCT02432885
Marly Conceição Silva, Tiago Augusto Magalhães, Zilda Maria Alves Meira, Carlos Henrique Reis Esselin Rassi, Amanda Cristina de Souza Andrade, Paulo Sampaio Gutierrez, Clerio Francisco Azevedo, Juliana Gurgel-Giannetti, Mariz Vainzof, Mayana Zatz, Roberto Kalil-Filho, Carlos Eduardo Rochitte. Myocardial Fibrosis Progression in Duchenne and Becker Muscular DystrophyA Randomized Clinical Trial. JAMA Cardiol. 2017;2(2):190–199. doi:10.1001/jamacardio.2016.4801