The Heart in Human Dystrophinopathies

Abstract

Dystrophinopathies are due to mutations in the dystrophin gene on chromosome Xp21.1 and comprise the allelic entities Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD) and X-linked dilative cardiomyopathy (XLDCM). In all three entities, the heart is affected to various degrees, depending on the stage of the disease and the type of the mutation (cardiac involvement, CI). The pathoanatomic evidence of CI in dystrophinopathies is the replacement of myocardium by connective tissue or fat. In DMD/BMD, the left ventricular posterobasal and lateral walls are most extensively affected, sparing the right ventricle and the atrium. Degree and dynamics of CI vary among the three entities. In DMD/BMD, CI usually remains subclinical in the early stages of the disease. Typical initial manifestations of CI in DMD/BMD are sinus tachycardia, tall R1 in V1, prominent Q in I, aVL, V6 or in II, III, and aVF, increased QT dispersion and possibly autonomic dysfunction. Initially, echocardiography is normal or shows regional wall motion abnormalities in areas of fibrosis. With spreading of fibrosis, left ventricular dysfunction and ventricular arrhythmias additionally occur. In the final stages of the disease, systolic function may lead to heart failure and sudden death. Subclinical or clinical CI is present in about 90% of the DMD/BMD patients but is the cause of death in only 20% of the DMD and 50% of the BMD patients. XLDCM is a rapidly progressive, almost exclusively myocardial disorder, starting in teenage males as heart failure due to dilative cardiomyopathy (CMP), leading to death from intractable heart failure within 1–2 years after diagnosis. Therapy of arrhythmias and CMP in all three disorders follows the established cardiological recommendations. Due to its protective effect, ACE inhibitors are recommended already at the early stages of the disease. β-Blockers may be an additional option if indicated.