End-stage heart failure is increasingly becoming the main cause of death in patients with Duchenne muscular dystrophy (DMD). Because cardiomyopathy, an abnormal heart condition, is difficult to detect, a study examined current diagnostic methods, treatment options, and potential future therapies for heart failure among patients with DMD, the most common type of muscular dystrophy.
The study, “A current approach to heart failure in Duchenne muscular dystrophy,” appeared in the journal Heart. Domenico D’Amario, from the Catholic University of the Sacred Heart’s Institute of Cardiology, in Rome, Italy, led the research.
DMD is caused by genetic mutations that result in the absence of a protein called dystrophin. DMD also affects cell biology in the heart tissue and causes an increase in intracellular calcium levels, which leads to the degradation of contractile proteins and promotes cellular death and fibrosis, or tissue scarring.
DMD impairs the ability to walk, decreases respiratory function, and ultimately, leads to heart failure in the third or fourth decade of life.
Although the frequency and severity of cardiovascular complications in DMD patients depend on the specific mutation in the DMD gene and may vary within the same mutation, progressive changes in heart functioning typically include arrhythmias, congestive heart failure, and dilated cardiomyopathy, a disease of the heart muscle.
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Diagnosing cardiovascular disease in DMD patients is difficult because it progresses slowly. Most patients do not show the classic symptoms of heart failure, which often leads to delays in evaluation, referral to cardiology units, and initiation of treatment.
Therefore, early diagnosis of cardiomyopathy in DMD patients is critical and may attenuate symptoms of heart failure. Current procedures include an initial cardiac assessment when a patient is 6 years old, and then biannually until the age of 10 or until symptoms occur. Subsequent annual evaluations should follow. Arrhythmias associated with left-ventricular dysfunction and myocardial fibrosis also should be investigated, given their reported prevalence.
Prevention of left-ventricular dysfunction should be started before the onset of symptoms, the review notes. Current therapy options include inhibitors of the renin-angiotensin system, which are used as first-line therapy, along with corticosteroid treatment, COX-inhibiting nitric oxide donors (a class of drugs that is similar to non-steroidal anti-inflammatory drugs, but better able to transport nitric oxide), and beta-blockers.
Mechanical cardiac support with left-ventricular assist devices (LVAD) is a possible treatment for end-stage heart failure in DMD, as these patients usually are not recommended for cardiac transplants due to progressive myopathy and limited functional capacity. However, the insufficient availability of LVAD devices and the lack of prospective studies with large follow-up periods evaluating their use in DMD is a concern. Therefore, a careful preoperative, multidisciplinary study of patients is necessary.
New therapies also are being developed, including sophisticated molecular biology approaches that use gene therapy to restore dystrophin production, or cell therapy involving healthy cell transplants to DMD patients. Recently, the U.S. Food and Drug Administration approved for the treatment of DMD the compounds Translarna (ataluren) and Exondys 51 (eteplirsen), which target cellular dysfunctions and ameliorate DMD phenotype.
Given the lack of specific genetic or cell-based therapies for DMD, “work in this area should focus on … the implementation of current recommendations in the prevention and early treatment of DMD cardiomyopathy,” and “the role of mechanical cardiac support in patients with end-stage” heart failure, the review’s authors wrote.