Treating Duchenne and Becker’s muscular dystrophy patients with angiotensin-converting enzyme (ACE) blocking drugs at early disease stages may slow the development of heart fibrosis and, as a consequence, offer patients a better prognosis.
Those findings are in the study “Myocardial Fibrosis Progression in Duchenne and Becker Muscular Dystrophy,” which was published in the journal JAMA Cardiology. It also showed that detection of fibrosis using magnetic resonance imaging (MRI) of the heart, better predicted heart problems in patients than conventional heart examinations, such as electrocardiography.
Researchers at the University of São Paulo Medical School in Brazil previously had investigated heart fibrosis in the two types of muscular dystrophies with the help of cardiovascular magnetic resonance scans. To explore whether ACE blockers — a type of medicine used to treat high blood pressure — may impact the outcomes of patients, the team designed a Phase 3 clinical trial (NCT02432885).
The trial randomized 42 muscular dystrophy patients with heart fibrosis, but preserved heart output, to receive the ACE blocker Enalapril (marketed as Epaned or Vaster), or no treatment. The majority, 39 patients, had Duchenne muscular dystrophy, and the mean age was 12.1 years.
All participants underwent a heart scan at the study start, and then again after two years. Researchers noted that the untreated patients had a significantly larger increase in fibrosis — 10% compared to only 3.1% in the treated group.
The increase in fibrosis did not lead to a significant change in the fibrosis percentage of left ventricular mass among treated patients. Untreated patients, on the other hand, had increased their proportion of fibrosis to the total mass of the left ventricle.
Corticosteroid treatment was not linked to the amount of fibrosis at study start, and did not impact the rate of fibrosis development. In contrast, an analysis showed that treatment was the only predictor of preserved left ventricle ejection fraction (the proportion of blood that leaves the heart during each contraction).
Researchers also studied how heart disease developed in two other groups of patients; 13 patients with a poor heart function, defined as an ejection fraction of less than 50%, and 21 patients with a preserved heart function and no fibrosis. The first group received heart medications in addition to standard muscular dystrophy care.
The study showed that while patients in the first group developed more fibrosis over time, those without fibrosis at the study’s start did not. This finding may have been influenced by age, because age could predict fibrosis both at study start and at the follow-up two years later.
Also, researchers noted that as fibrosis increased with age, levels of creatine kinase decreased. Among those patients, the team could not see that corticosteroid treatment impacted fibrosis development.
The presence of fibrosis, however, could indicate that a patient would fare worse than those without. Four patients died during the study, and fibrosis levels in these four were significantly higher than in those who did not die.
Also, patients with fibrosis had a higher risk of experiencing heart problems compared to those without. Researchers also showed that the traditional heart measures chest radiography, electrocardiography, and echocardiography were not sensitive in detecting heart fibrosis. These methods also could not predict if patients would experience heart problems.