Managing dystrophinopathic cardiomyopathy

Heart transplantation in patients with dystrophinopathic cardiomyopathy: Review of the literature and personal series

“…Absence, reduced levels or abnormal structure of dystrophin lead to membrane fragility, making muscle fibres more prone to injury during contraction (6). As muscle disease progresses, muscle repair cannot adequately compensate for damage, leading to necrosis of skeletal and cardiac myocytes and the progressive replacement by fibro-fatty tissue (7)(8)(9)(10)(11)(12)(13)(14)(15). Dystrophinopathies include four different clinical presentations: Duchenne muscular dystrophy (DMD), the more severe form, Becker muscular dystrophy (BMD), the more benign form, the X-linked dilated cardiomyopathy (XL-dCM) (8) and the cardiomyopathy of DMD/BMD carriers.…”

“…Cardiac death usually occurs from ventricular dysfunction and dilated cardiomyopathy, that represents the end-stage of dystrophinopathic cardiomyopathy (DCM) (10)(11)(29)(30). DCM is constantly progressive and evolves in a stage-wise manner, passing from a presymptomatic condition to dilated cardiomyopathy through a number of pathophysiologically distinct stages (10,11) (Figure 1). …”

Chloroquine decreases cardiac fibrosis and improves cardiac function in a mouse model of Duchenne muscular dystrophy

“…Recent reports have demonstrated that the mean lifespan of DMD patients is as high as 35 years of age and that more than half of DMD patients die from cardiomyopathy [12][13][14]. To improve the prognosis of DMD-related cardiomyopathy, mechanistic and therapeutic studies to yield more targeted approaches to treatment are necessary.…”

“…Fibrosis-associated cardiomyopathy generally leads to dilated cardiomyopathy. More than 80% of DMD patients older than 18 years have reduced cardiac function, and 90% of DMD patients develop dilated cardiomyopathy [ 13 , 14 ]. General therapeutic protocols for dilated cardiomyopathy secondary to DMD are not curative, e.g.…”

238th ENMC International Workshop: Updating management recommendations of cardiac dystrophinopathyHoofddorp, The Netherlands, 30 November - 2 December 2018

“…Sacubitril-valsartan ('Entresto') may be able to improve on the benefits of ACE-inhibitor therapy but this has yet to be tested in DMD [18] . Although there is good rationale for adding prophylactic beta-blocker therapy to an ACE-inhibitor, the evidence for this is less clear [19][20][21] .…”