Duchenne and Becker muscular dystrophy carriers: Evidence of cardiomyopathy by exercise and cardiac MRI testing.
BACKGROUND
Varied detection methods have resulted in conflicting reports on the prevalence of cardiac disease in Duchenne and Becker muscular dystrophy carriers (MDC).


METHODS
We performed a prospective cohort study of 77 genetically-confirmed MDC mothers, 22 non-carrier mothers, and 25 controls. All participants underwent Cardiopulmonary Exercise Testing (CPET) and Cardiac Magnetic Resonance imaging (CMR).


RESULTS
25% of carriers had ventricular ectopy in recovery of exercise (RecVE) as compared to 1 non-carrier and no controls (p = .003). No difference in age or maximal oxygen consumption was noted. 11 carriers had abnormal (<55%) left ventricular ejection fraction by CMR. Evidence of late gadolinium enhancement (LGE) was noted in 48% of MDC, 1 non-carrier patient and no control subjects (p < .0001). Subset analysis of LGE+ and LGE- subjects revealed differences in age (44.1 v 38.6 yrs.; p = .005), presence of RecVE, (38.9% v 10.5%, p = .004), and high serum creatine kinase (CK) (> 289 U/l; 52.8% v 31.6%, p = .065).


CONCLUSION
We describe the prevalence of disease using CPET and CMR in genetically-proven MDC. 49% of carriers had fibrosis, opposed to 5% of non-carriers, highlighting the importance of genetic testing in this population. Despite cardiomyopathy, functional assessment by treadmill was normal, illustrating the discrepancy in cardiac and skeletal muscle impacts. Age, RecVE and serum CK appear to have an important role in predicting cardiomyopathy. Serum CK levels suggest that a systemic higher global disease severity and not tissue heterogeneity may be the etiology for greater cardiac disease and relatively spared skeletal muscle disease in this population. Clinical Trial Registration https://clinicaltrials.gov/ct2/show/NCT02972580?term=mendell&cond=Duchenne+Muscular+Dystrophy&rank=5; ClinicalTrials.gov Identifier: NCT02972580.
['Mah|May Ling|ML|', 'Cripe|Linda|L|', 'Slawinski|Michelle K|MK|', 'Al-Zaidy|Samiah A|SA|', 'Camino|Eric|E|', 'Lehman|Kelly J|KJ|', 'Jackson|Jamie L|JL|', 'Iammarino|Megan|M|', 'Miller|Natalie|N|', 'Mendell|Jerry R|JR|', 'Hor|Kan N|KN|']
D000328:Adult D009202:Cardiomyopathies D003287:Contrast Media D005682:Gadolinium D006801:Humans D008279:Magnetic Resonance Imaging D019028:Magnetic Resonance Imaging, Cine D020388:Muscular Dystrophy, Duchenne D011446:Prospective Studies D013318:Stroke Volume D016277:Ventricular Function, Left
Cardiomyopathy Cardiac magnetic resonance imaging Ventricular ectopy Late gadolinium enhancement Duchenne carrier Peak oxygen uptake T1 mapping