LV Structure and Function in Duchenne Muscular Dystrophy Female Carriers

Duchenne muscular dystrophy (DMD) is a rare X-linked neuromuscular disorder affecting 1 in 5,000 live male births worldwide and resulting in permanent injury to the skeletal muscle and the heart due to the loss of dystrophin. Although the median life expectancy of DMD male patients has increased from 22 years in the mid-1990s to 28 years in 2021, the majority of DMD male patients currently succumb to complications related to advanced cardiomyopathy. Unfortunately, a limited number of studies have focused on the cardiovascular health of DMD female carrier patients.

Previously, we demonstrated that the majority of DMD female carrier patients developed subclinical cardiomyopathy. During #AHA21, we presented a new study regarding the induction of reverse cardiac remodeling in DMD female carrier patients. Specifically, we reported that DMD female carriers with reduced left ventricular ejection fraction (LVEF) showed significant improvement in LVEF and LV end-systolic volume following at least one year of treatment with an RAAS antagonist.

In a separate study, we observed that muscular dystrophy patients with normal or reduced LVEF had lower indexed LV mass and LV concentricity as compared to a matched healthy control population derived from the Dallas Heart Study. This observation held true for DMD female carriers as well. These data suggest that the lower LV mass and LV concentricity represent cardiac hypoplasia and/or atrophy.

Our work demonstrates a cardiac phenotype in DMD female carriers and highlights the importance of initiating RAAS inhibition in this patient population. Our ongoing clinical and translational research are being conducted in parallel with the groundbreaking work on the use of genome editing as a novel treatment for DMD patients by Dr. Eric Olson’s group at UT Southwestern. We anticipate that this collaborative work, forged within the UT Southwestern Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, will pave the way for future therapies for both DMD and DMD-carrier patients.