Heart Disease in Disorders of Muscle, Neuromuscular Transmission, and the Nerves

Abstract

Little is known regarding cardiac involvement (CI) by neuromuscular disorders (NMDs). The purpose of this review is to summarise and discuss the major findings concerning the types, frequency, and severity of cardiac disorders in NMDs as well as their diagnosis, treatment, and overall outcome. CI in NMDs is characterized by pathologic involvement of the myocardium or cardiac conduction system. Less commonly, additional critical anatomic structures, such as the valves, coronary arteries, endocardium, pericardium, and even the aortic root may be involved. Involvement of the myocardium manifests most frequently as hypertrophic or dilated cardiomyopathy and less frequently as restrictive cardiomyopathy, non-compaction, arrhythmogenic right-ventricular dysplasia, or Takotsubo-syndrome. Cardiac conduction defects and supraventricular and ventricular arrhythmias are common cardiac manifestations of NMDs. Arrhythmias may evolve into life-threatening ventricular tachycardias, asystole, or even sudden cardiac death. CI is common and carries great prognostic significance on the outcome of dystrophinopathies, laminopathies, desminopathies, nemaline myopathy, myotonias, metabolic myopathies, Danon disease, and Barth-syndrome. The diagnosis and treatment of CI in NMDs follows established guidelines for the management of cardiac disease, but cardiotoxic medications should be avoided. CI in NMDs is relatively common and requires complete work-up following the establishment of a neurological diagnosis. Appropriate cardiac treatment significantly improves the overall long-term outcome of NMDs.

Keywords: Cardiac arrhythmias; Cardiomyopathies; Muscular diseases; Neuromuscular disease.

Fig. 1. Echocardiographic 4-chamber view in a patient with a mitochondrial disorder showing apical left ventricular hypertrabeculation/noncompaction.

Fig. 2. Transthoracic echocardiography showing apical ballooning, akinesia, and reduced systolic function in a patient with a mitochondrial disorder.

Fig. 3. Left ventricular endomyocardial biopsy. Electron microscopy revealing an excessive number of mitochondria of variable size with an abnormal morphology and vacuoles containing glycogen and degenerated mitochondria. N: nucleus, Bar: 1 µm (reproduced with permission applied from Nakagawa et al.192)).

Fig. 4. Late Gadolinium enhancement-cardiac magnetic resonance images in midventricular short-axis and 3-chamber-views from two muscular dystrophy patients with different stages of cardiomyopathy. Upper panel images show subepicardial late Gadolinium enhancement (LGE) as the only sign of cardiac involvement in a 22 year Becker muscular dystrophy patient. Lower panel images show transmural LGE but only mildly impaired left ventricular systolic function in a 27 year Duchenne muscular dystrophy patient with non-sustained ventricular tachycardia (reproduced with permission from Florian et al.143)).

Fig. 5. Two-dimensional echocardiogram, parasternal long-axis view showing marked concentric hypertrophy with a non-dilated ventricle in a male with mitochondrial hCMP due to the mutation m.3303T>C (reproduced with applied permission from Palecek et al.193)). hCMP: hypertrophic cardiomyopathy.