Cardiac Involvement in Patients With Muscular Dystrophies

Muscular dystrophy (MD) connotes a heterogeneous group of inherited disorders characterized by progressive wasting and weakness of the skeletal muscles. In several forms of MD, cardiac dysfunction occurs, and cardiac disease may even be the predominant manifestation of the underlying genetic myopathy. Cardiologists may be unfamiliar with these diseases owing to their low incidence; also, significant advances in respiratory care have only recently unmasked cardiomyopathy as a significant cause of death in MD.1Early detection of MD-associated cardiomyopathy is important, because institution of cardioprotective medical therapies may slow adverse cardiac remodeling and attenuate heart failure symptoms in these patients.2–6 Although ECG and echocardiography are typically advocated for screening,7,8 cardiovascular magnetic resonance (CMR) has shown promise in revealing early cardiac involvement when standard cardiac evaluation is unremarkable.9,10This review will focus on 4 groups of skeletal muscle disease most commonly associated with cardiac complications (the Table): (1) dystrophin-associated diseases such as Duchenne and Becker (DMD and BMD, respectively), (2) Emery-Dreifuss MD (EDMD), (3) limb-girdle MD (LGMD), and (4) myotonic dystrophy (DM).View this table:Table. Characteristics of the Types of MD Molecular and Genetic FeaturesDMD and BMD are X-linked disorders affecting the synthesis of dystrophin, a large, sarcolemmal protein that is absent in DMD11 and reduced in amount or abnormal in size in BMD patients.12 Dystrophin provides the connection between a large, multimeric complex of glycoproteins in the muscle cell membrane (termed the dystrophin-glycoprotein complex) and intracellular actin filaments (Figure 1), thereby transmitting forces generated by sarcomere contraction to the extracellular matrix.13,14 Correlations between dystrophin mutations and the onset of cardiomyopathy have been noted15; some mutations result in only cardiomyopathy without skeletal myopathy.16 Other proteins not shown in Figure 1 that are particularly involved in both inside-out and outside-in transmission …