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Sophie Mavrogeni ,
Duchenne and Becker muscular dystrophies are inherited X-linked, recessive disorders characterised by an abnormality in the dystrophin gene and in which elevated serum creatinine kinase activity is observed. Duchenne patients die in their 20s while Becker patients survive to age 40-50. In addition to corticosteroid treatment, a preventive use of ACE-inhibitors at 9yrs of age, when the heart is still normal, postpones the development of cardiomyopathy. Magnetic resonance imaging has been proposed as a non-invasive method of monitoring these patients and guiding treatment.
Duchenne Muscular Dystrophy (DMD) patients
Becker Muscular Dystrophy (BMD) patients
Both Duchenne (DMD) and Becker (BMD) muscular dystrophies are X-linked, recessive disorders in which the genetic locus has been identified as an abnormality in the dystrophin gene.
The dystrophin gene
The dystophin protein provides a structural link between myocyte cytoskeleton and extracellular matrix functioning to link contractile proteins to the cell membrane. Abnormal dystrophin has also been identified as a potential susceptibility gene for viral infection and as factor that markedly increases enterovirus induced cardiomyopathy (2). In DMD, the dystrophin is nearly absent, whereas in BMD the dystrophin is present but reduced in size or amount (1).
DMD is the most common inherited neuromuscular disorder, with an incidence of 30 per 100,000 live male births. Patients :
All DMD patients develop cardiomyopathy, but clinical recognition may be masked by severe muscle weakness. Thoracic deformities can also alter the cardiovascular evaluation in DMD.
A reduction in the anteroposterior chest dimensions is usually responsible for a systolic impulse displaced to the left sternal border, a grade 1-3/6 short mid-systolic murmur in the second left interspace and a loud pulmonary component of the second heart sound. Mitral regurgitation is related to posterior papillary muscle dysfunction.Additionally, the sudden onset of cardiac symptoms accompanied by deterioration of left ventricular function in young DMD patients already on treatment with a prednisone derivate, that postpones the development of DMD cardiomyopathy, should raise the suspicion of possible myocarditis (3).
The ECG is abnormal in 90% of cases, demonstrating tall R waves, increased RS in V1 and deep narrow Q waves in left precordial leads. Sinus tachycardia is the commonest abnormality. Atrial fibrillation, flutter and ventricular premature complexes can also be found.
is less common (3 per 100,000 live male births) and has a more variable presentation of skeletal muscle weakness and a better prognosis, with most patients surviving to age 40-50 years.
Cardiac involvement is independent of the severity of skeletal muscle disease. More than half of all patients with sub-clinical or benign skeletal muscle disease were noted to have cardiac manifestations.
Cardiomyopathy can initially involve the right ventricle solely. The presence of mitral regurgitation is due to mitral annulus dilatation. The ECG is abnormal in 75% of cases, demonstrating tall R waves, increased RS in V1 and deep narrow Q waves in left precordial leads and or incomplete right bundle branch block. In both diseases elevated serum creatinine kinase activity is observed (over 5-10 fold normal values).
Magnetic resonance imaging (MRI) has been proposed as a readily available, non-invasive method of monitoring tissue structure in these patients. Unlike other modalities, MRI has non-ionizing radiation, produces high-resolution images and can be used for quantitative tissue characterisation by measuring the T2 relaxation time of muscles. In patients with DMD, the T2 relaxation time in peripheral muscles was significantly different from that measured in healthy controls, essentially reflecting differences in fat and water composition between diseased and healthy muscles.
Because T2 relaxation time changes as the disease progresses, it could be used to monitor disease progression and possibly response to therapy in these patients. In our previous study, we assessed that MRI measurements of T2 relaxation time can detect differences in tissue composition between DMD patients without clinical evidence of cardio-respiratory symptoms and age-matched healthy volunteers (4).
Until treatment of the basic genetic defect becomes available, management depends on medical, surgical, and rehabilitative approaches that optimise and maintain patient function.
Many different medications have been tried as potential treatments for DMD, but only the corticosteroids prednisone and deflazacort have shown potential for providing temporary improvement, assessed mainly from slowing the rate of progression or stabilising muscle strength and function. Daily treatment with prednisone at a starting dosage of 0.75 mg/kg/day or deflazacort at a starting dosage of 0.9 mg/kg/day offers an optimal and effective initial treatment (5). The most frequent side effects are weight gain and development of a cushingoid facial appearance. The specific cellular events responsible for the beneficial effects of corticosteroid therapy in DMD are not known.
Studies using azathioprine as an alternative immunosuppressive treatment to prednisone showed no beneficial effect and suggested that the effects of prednisone observed in clinical studies are unlikely to result from its immunosuppressive actions.
Additionally, the prophylactic use of ACE-inhibitors is recommended from the age of 9 years and before the establishment of cardiomyopathy (6). Supportive treatment with ACE-inhibitors, diuretics, carvedilol and antiarrhythmic medication is recommended for cases presenting with heart failure.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.
1. Hoffman EP. Dystrophinopathies. In: Karpati G, Hilton-Jones D, Griggs R, eds. Disorders of voluntary muscle. Cambridge: Cambridge University Press, 2001: 385–432.
2. Badorff C, Knowlton KU. Dystrofin deficiency markedly increases enterovirus induced cardiomyopathy. Med Microbiol Immunol 2004; 193 (2-3): 121-6
3. Mavrogeni S, Papavassiliou A, Cokkinos DV. Myocarditis in a patient with Duchenne Muscular Dystrophy detected by cardiovascular magnetic resonance and cardiac biopsy. Int J Cardiol (in press)
4. Mavrogeni S, Tzelepis GE, Athanasopoulos G, et al. Cardiac and sternocleidomastoid muscle involvement in Duchenne muscular dystrophy: an MRI study. Chest. 2005; 127: 143-8
5. Mavrogeni S, Papavasiliou A, Douskou M, Kolovou G, Papadopoulou E, CokkinosDV. Effect of Deflazacort on Cardiac and Sternocleidomastoid muscles in Duchenne Muscular Dystrophy: A Magnetic Resonance Imaging Study. Eur J Ped Neurology (in press)
6. Duboc D, Meune C, Pierre B, Wahbi K, Eymard C, Toutain A, Berard C, Vaksmann G, Weber S, Becane HM. Perindopril preventive treatment on mortality in Duchenne Muscular Dystrophy: 10 yrs follow-up. Am Heart J 2007; 154(3): 596-602 .
Dr S. Mavrogeni Athens, Greece Nucleus Member of the ESC WG for Cardiovasular Magnetic Resonance
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