What are the effects of treatments used to prevent or treat heart complications in Duchenne muscular dystrophy, Becker muscular dystrophy, and X‐linked dilated cardiomyopathy? A Cochrane Review summary with commentary

The aim of this commentary is to discuss, from a rehabilitation perspective, the Cochrane Review ‘Interventions for preventing and treating cardiac complications in Duchenne and Becker muscular dystrophy and X-linked dilated cardiomyopathy’ by Bourke et al.1 published by the Cochrane Neuromuscular Disease Group. This Cochrane Corner is produced in agreement with Developmental Medicine & Child Neurology by Cochrane Rehabilitation. Dystrophinopathies are mainly X-linked inherited degenerative muscle disorders, which include Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and X-linked dilated cardiomyopathy (XLDCM). Despite other significant improvements in physical and respiratory management, cardiac involvement and its consequences have not changed.2 Cardiac complications, in the form of dilated cardiomyopathy with cardiac failure or ventricular arrhythmias, remain a common cause of death in DMD, with 40% to 50% of patients dying as a direct consequence.3 As cardiomyopathy is now the most important limiting factor for long-term survival among the BMD and DMD population, this review1 is important to determine the best available treatment to preserve or improve cardiac function and to enhance rehabilitation outcomes. The aim of this Cochrane Review was to assess the effects of interventions for preventing or treating cardiac involvement in DMD, BMD, and XLDCM. The population addressed in this review were children and adults of all ages, diagnosed as having a dystrophinopathy (DMD, BMD, or XLDCM) by muscle biopsy showing relevant dystrophin staining abnormalities and/or DNA studies showing relevant abnormalities in the dystrophin gene. Interventions included pharmacological and non-pharmacological treatments known to have an effect on improving or reversing adversely affected cardiac function. The primary outcome studied was the change in cardiac function after a 6-month period of intervention. The secondary outcomes included size of metabolically abnormal areas of myocardium identified with other forms of cardiac imaging, improvements in quality of life measures, and the occurrence of one or more adverse events. The review authors searched articles in the Cochrane Neuromuscular Specialised Register and CENTRAL up to 16th October 2017, MEDLINE and Embase up to 16th October 2016, two clinical trials registries (US National Institutes of Health Ongoing Trials register and World Health Organization International Clinical Trials Registry Platform) up to 30th August 2018 and 31st July 2018 respectively, as well as conference proceedings and bibliographies. The review included five studies with a total of 205 participants. Four studies included participants with DMD only and one study included participants with DMD or BMD. There were no studies involving XLDCM. The authors pointed to comparable beneficial effects of early treatment with ACE inhibitors or ARBs for people with a dystrophinopathy. Adding eplerenone might have additional benefit when early cardiomyopathy is detected. There was no clinically meaningful effect for growth hormone or idebenone. However, they acknowledged the certainty of evidence was very low. Coordinated multidisciplinary management in patients with dystrophinopathy has improved the quality of care, including prolonging independent ambulation and increasing survival.3 As most patients with dystrophinopathy will have cardiac involvement and its complications,3, 4 selecting the best treatment to prevent or treat cardiac complications is very important. Cardiac involvement and its complications influence the outcome of rehabilitation management, which mainly focuses on ambulation and independence in daily activities. In light of the very low-certainty evidence in the review,1 perindopril may prevent cardiac involvement. Adding eplerenone on top of ACE inhibitors or ARBs may reduce deterioration of cardiac function, but it cannot be certain if these are indeed the outcomes in real-life situations. Guided exercise can prevent sedentary lifestyles, and problems of social isolation and overweight among patients with dystrophinopathy.5 This evidence on pharmacological options is highly relevant in rehabilitation management, as better cardiac function will increase exercise capacity and overall outcome. The studies evaluated in the review did not assess the effects of these medications on health-related quality of life. This is very important, as health-related quality of life is significantly associated with disease progression.6 The authors thank Cochrane Rehabilitation and Cochrane Neuromuscular for reviewing the contents of the Cochrane Corner. The authors have stated that they had no interests that could be perceived as posing a conflict or bias.