Cardiomyopathy in Muscular Dystrophy: When to Treat?

Duchenne muscular dystrophy (DMD) is a rare, X-linked condition with progressive muscle weakness and accompanying cardiomyopathy. Cardiovascular magnetic resonance (CMR) has proved particularly useful for monitoring the earliest signs of cardiac involvement in DMD, including left ventricular (LV) strain defects and myocardial fibrosis, which appear before the onset of LV systolic dysfunction. Most patients with DMD develop cardiomyopathic features between ages 10 and 15 years. Because of this tight timeline during which heart dysfunction appears, DMD offers a unique opportunity to assess strategies to limit cardiomyopathy progression. Becker muscular dystrophy (BMD), like DMD, is caused by dystrophin mutations and often also includes dilated cardiomyopathy but with variable progression.

In this issue of JAMA Cardiology, Silva and colleagues evaluated a cohort of 76 patients with DMD or BMD (mean [SD] age, 13.1 [4.4] years) using CMR.¹ Myocardial fibrosis was most commonly seen midepicardially and subepicardially and tended to occur in inferior and lateral walls. Myocardial fibrosis correlated with systolic function, and patients with poor outcomes had more extensive myocardial fibrosis. Forty-two individuals had myocardial fibrosis but preserved function (LV ejection fraction ≥50%) and were randomized to treatment with enalapril or no enalapril. After 2 years, the treated group had slower progression of myocardial fibrosis determined with CMR. The findings provide support for the concept of pretreating cardiomyopathy before the onset of LV dysfunction.

Early treatment of cardiomyopathy in DMD has been advocated based on nuclear imaging of a distinct but similar-age DMD population.² In addition to angiotensin-converting enzyme inhibitors, treatment with eplerenone has been shown to reduce LV strain defects in DMD.³ Together, these studies provide sound evidence for early intervention to prevent or slow cardiomyopathy progression with medical management. Moreover, this recommendation was the consensus from a working group meeting convened by the National Heart, Lung, and Blood Institute and Parent Project Muscular Dystrophy on the cardiac management of DMD.⁴

Clinical trials in rare diseases have the advantage of using well-defined homogeneous populations but are often limited by small sample size. Nonetheless, in some settings it may be reasonable to extrapolate from rare disease findings to other groups. With the increasing availability of genetic testing for dilated cardiomyopathy, there is now emerging a group of younger, gene mutation–positive individuals who are prone to developing cardiomyopathy and ultimately heart failure. These gene mutation–positive individuals are most often discovered through cascade genetic testing of a family member with cardiomyopathy. Data are lacking on whether early treatment would similarly benefit this group, but the present investigation indicates that this issue should be addressed. As we move closer to using genetic signatures to identify individuals at risk and applying tailored therapy, we realize a goal of personalized medicine.

Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.