Progression of Myocardial Fibrosis in MD Patients Slowed with ACE Inhibitors

Patients with Duchenne muscular dystrophy and Becker muscular dystrophy treated with ACE inhibitors inhibitors (drugs that dilate blood vessels) had slower progression of myocardial fibrosis than those treated with usual care.

The study with the findings, “Myocardial Fibrosis Progression in Duchenne and Becker Muscular Dystrophy: A Randomized Clinical Trial,” is published in JAMA Cardiology.

Cardiac fibrosis refers to an abnormal thickening of the heart valves due to a proliferation of cardiac fibroblasts, and refers to the growth of fibroblasts in the cardiac muscle. Fibrotic cardiac muscle is stiffer and less compliant and is seen in the progression to heart failure.

ACE inhibitors widen blood vessels, increasing blood flow, which leads to lower blood pressure and decreased oxygen demand from the heart.

To assess the effect of early ACE (angiotensin-converting enzyme) inhibitor therapy in patients with normal LV (left ventricular) function on the progression of myocardial fibrosis (MF), Marly Conceição Silva, MD, PhD, from the Heart Institute, University of São Paulo Medical School in Brazil and colleagues, conducted randomized clinical trial in 76 male patients with Duchenne MD or Becker MD undergoing cardiovascular magnetic resonance (CMR) assessments with a two-year interval for ventricular function and MF evaluation.

Of the 76 patients included in the study, 70 had Duchenne MD and six had Becker MD. Myocardial fibrosis was present in 55 patients and left ventricle systolic dysfunction was identified in 13 patients. Some of these patients were not included in the randomized comparison because they had abnormal ventricular function or no myocardial fibrosis at study entry.

The researchers randomized 42 patients with MF and normal left ventricular ejection fraction (LVEF) to either receive or not receive ACE inhibitors.

The primary endpoint was progression of myocardial fibrosis from baseline to two years as assessed by CMR.

The researchers found that patients who received ACE inhibitors had slower progression of myocardial fibrosis at two years compared with patients who received usual care.

Results from a multivariable analysis showed that treatment with ACE inhibitors independently predicted decreased progression of myocardial fibrosis.

When researchers performed statistical analyses considering the entire cohort of patients, they found that patients with myocardial fibrosis (confirmed by CMR) were more likely to have cardiovascular events than those who did not (18.2% versus 0%, respectively).

Elizabeth M. McNally, MD, PhD, director of the Center for Genetic Medicine at Northwestern University Feinberg School of Medicine and associate editor for translational science of JAMA Cardiology, wrote in an accompanying editorial, “The findings provide support for the concept of pretreating cardiomyopathy before the onset of LV dysfunction.”

While there is some debate over prophylactic treatment for young people with a genetic mutation that puts them at increased risk for dilated cardiomyopathy and MF, “the present investigation indicates that this issue should be addressed,” McNally wrote.