**1. Introduction**

Dilated cardiomyopathy (DCM), arrhythmias, and congestive heart failure (HF) represent the most important life-limiting condition in Duchenne muscular dystrophy (DMD) [1–3].

Routinely cardiovascular evaluation including echocardiography is recommended in the current 2018 DMD Care consideration sponsored by Centers of disease control and prevention [4]. Moreover, HF treatments have evolved tremendously since 1980s and the armamentarium of adult HF specialists has been enriched with new drugs and the use of device (i.e., cardiac resynchronization therapy, intracardiac defibrillator, and ventricular assist device) before cardiac transplant. DMD patients are not usually candidate for heart transplantation because of the progressive skeletal myopathy, limited functional capacity [5], and shortage of donor availability.

In this review, we present the cardiologist perspective on current data regarding clinical management of DMD patients.

#### **2. Pathophysiology of DMD-DCM**

DMD is an X-linked recessive disorder occurring in one in 3500 male births. It is caused by mutations in the dystrophin gene that result in marked reduction or absence of the sarcolemmal protein dystrophin.

DMD belongs to the group of dystrophinopathies, characterized by different pathogenic conditions and variable degrees of skeletal and cardiac muscle impairment. Typically, DMD is the most severe form while Becker muscular dystrophy (BMD) is the more benign form along with the X-linked DCM (XL-DCM) [6,7] and the cardiomyopathy of DMD/BMD carriers [8].

Several patho-mechanisms are involved in the cellular damage initially caused by the lack of dystrophin, in both skeletal and cardiac muscles. Normally dystrophin provides structural support for the myocyte and sarcolemmal membrane by its linking of actin at the C amino-terminus with the dystrophin-associated protein complex and sarcolemma at the carboxyl-terminus and the extracellular matrix of muscle [9,10]. Dystrophin is also present in T-tubular membranes of cardiac myocytes. Thus, it is involved in the maintenance of membrane stability and in the transduction of mechanical force from the sarcomeres to the extracellular matrix. The absence of the dystrophin leads to an extreme vulnerability of the cellular membranes; cellular stress could be directly mediated by the lack of dystrophin, or indirectly via intracellular Ca2<sup>+</sup> overload or oxidative stress. The activation of these damaging cellular pathways and Ca2<sup>+</sup> signaling pathways lead to dystrophic DCM [11]. As muscle disease progresses, skeletal and cardiac myocytes necrotize and mechanisms of repair are not adequate, with consequent progressive replacement by fibrofatty tissue [12].

DMD-DCM is characterized by thinner left ventricle (LV) wall and progressive LV dilatation, reflecting the ongoing myocyte loss [1,5]. In particular the repetitive mechanical stress leads to apoptosis and fibrotic substitution and scarring that proceeds from the epicardium to the endocardium, starting generally at the region behind the posterior and mitral valve apparatus. This scarring spreads downward progressively toward the apex and around the heart, ultimately leading to DCM [13,14].
