Cardiac magnetic resonance in patients with muscular dystrophies: strengthening the data

Muscular dystrophies (MDs) are genetically inherited, primary degenerative disorders of the muscle. The word ‘dystrophy’ is derived from the Greek words ‘δυσ-’ meaning bad/faulty and ‘τροφή’ meaning nourishment, and is used to describe the progressive muscle degeneration and weakness associated with MDs as well as the dystrophic changes of fibre necrosis and eventually replacement by connective tissue and fat on muscle biopsy. MDs comprise a heterogeneous group with different inheritance patterns and pathogenetic abnormalities, and variable disease onset, severity and distribution of predominant muscle weakness. Disease progression and life expectancy also vary considerably.1,2 MDs can be classified into congenital forms presenting at birth or during the first few months of life, and later onset conditions including Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), Emery–Dreifuss muscular dystrophy (EDMD), facioscapulohumeral, distal, oculopharyngeal muscular dystrophy and the heterogeneous group of limb–girdle muscular dystrophies (LGMDs). The X-linked DMD, with complete absence of the sarcolemmal protein dystrophin, and its milder allelic condition BMD represent the most common types of MDs in children. Myotonic dystrophy (dystrophia myotonica; DM) is an autosomal dominant muscular dystrophy associated with stiffness of various muscles (myotonia) and is the most frequent form in adults.1–3 Cardiac involvement is common in many forms of MDs and may be a predominant feature in the absence of clinically significant weakness, even in carriers of the disease.1,4 Cardiomyopathy in MDs is generally the result of the same mutational event that leads to skeletal muscle degeneration,5 although alternative mechanisms including sympathovagal imbalance and ergoreflex sensitivity have been proposed.6 The main features are myocardial fibre degeneration and fibrosis which may be ‘patchy’, ‘streaky’ or diffuse, mainly involving the subepicardial layer of the left ventricular wall, with some component of fatty infiltration.7 Right ventricular involvement is less frequent, but in some cases it might even precede the impairment in left ventricular function.8 In DMD, BMD and some forms of LGMD, dilated cardiomyopathy is the main cardiac complication and is the leading cause of death. Patients with DM, EDMD and some types of LGMD are at increased risk of sudden cardiac death (SCD) due to conduction abnormalities and cardiac arrhythmias; implantation of cardiac pacemaker/implantable cardioverter defibrillator is usually required.2,9 However, due to the relatively low incidence of MDs and the delayed or clinically silent cardiac involvement because of physical inactivity, cardiologists outside expert care centres have only recently started to familiarise themselves with cardiac complications in these patients. Factors that have contributed to this are the significant advances in respiratory care leading to improved survival rates, increased cardiac screening of patients and relatives using advanced imaging techniques, and an overall enhanced understanding of the importance of cardiac involvement. Cardiac magnetic resonance imaging (CMR) offers an invaluable tool for the accurate and reproducible assessment of cardiac volumes and function, without any geometric assumptions, limitations from chest wall/spinal deformities or lung disease and without ionising radiation. In patients with MDs, CMR is the only imaging modality that can detect focal or diffuse myocardial fibrosis with late gadolinium enhancement (LGE) or parametric mapping, assess for fatty infiltration of the myocardium and detect myocardial oedema. Furthermore, myocardial strain analysis can reveal subclinical myocardial dysfunction even in patients with preserved ejection fraction.10 In this issue of the European Journal of Preventive Cardiology, Grigoratos et al.11 try to summarise CMR findings in patients with MDs and attempt to provide practical recommendations on the use of CMR for diagnosis, risk stratification, follow-up and long-term prognosis. The authors should be congratulated for providing a concise contemporary summary of the available literature, despite the paucity of multicentre data and the small number of patients evaluated with CMR in most studies. The main CMR findings in patients with MDs, as described in the review by Grigoratos et al., can be summarised as follows: (a) Patients with MDs demonstrate areas of focal fibrosis, which is usually subepicardial or mid-wall but can progress to transmural scar. Fibrotic areas are most commonly located in the inferolateral wall in patients with DMD, BMD and some forms of LGMD, in the basal inferior/inferolateral/septal walls in patients with facioscapulohumeral muscular dystrophy, while no specific preferential location has been reported for DM. In small cohorts of patients with EDMD evaluated with CMR, no areas with LGE enhancement were demonstrated. (b) The presence and extent of LGE is associated with myocardial dysfunction, disease progression, the occurrence of arrhythmias and has been shown to predict mortality in patients with DMD and BMD; data are limited and findings inconclusive for other MD forms. (c) T1 mapping techniques can detect diffuse myocardial fibrosis even in the absence of focal fibrosis on LGE imaging. (d) Myocardial strain is impaired even before the decline in ejection fraction. Despite its rather broad and descriptive nature, the review contributes to existing CMR literature in patients with MDs. Based on the available knowledge, the authors provide suggestions on the clinical use of CMR in patients with MDs, taking into consideration the advantages over echocardiography but also the challenges in patients with severe respiratory or mobility problems. In particular, (a) CMR can be useful in detecting early cardiac involvement in patients with established MD, carriers of disease-causing mutations and patients undergoing diagnostic work-up for skeletal myopathy of unknown origin. (b) CMR is probably of less added benefit in patients with advanced muscle and/or cardiac involvement, already portending a poor prognosis. (c) The presence of impaired left ventricular systolic function and/or myocardial fibrosis can guide the initiation of treatment, because the early detection of cardiomyopathy and initiation of anti-heart failure therapy may attenuate the progressive decline in cardiac function.12 (d) Strain imaging, LGE and potentially parametric CMR mapping can improve the prediction of heart failure and arrhythmic events. As the authors point out, the challenge is to identify predictors of SCD with CMR. (e) Due to its unsurpassed accuracy and reproducibility in defining cardiac morphology and function, CMR can be helpful in the long-term follow-up, to monitor disease progression and response to treatment. The above suggestions are in agreement with recently published scientific statements and recommendations.3,13–15 The role of CMR in the assessment of patients with MDs is continuously evolving; however, the utility of CMR in all forms of MD has not yet been established. As the authors emphasise, large-scale multicentre prospective studies using dedicated CMR protocols are needed to evaluate the correlation of CMR findings to clinical outcomes and establish their possible association with heart failure, conduction abnormalities/arrhythmias and the risk of SCD. Assessment of global and regional myocardial deformation with strain imaging and interrogation of myocardial energetics with magnetic resonance spectroscopy may help further elucidate underlying causal mechanisms and unmask early cardiac involvement. To conclude, although cardiac involvement is common in several forms of MDs, significant gaps remain in our understanding of the pathophysiology of cardiac implications and particularly the ability to predict cardiac events. CMR can provide valuable information about anatomy, function, tissue composition and myocardial metabolism and energetics, with a few limitations in patients with MDs which can be overcome with newer and evolving CMR techniques (Table 1). At the same time, the increased recognition of myocardial changes with CMR raises challenging questions about their potential role in the clinical management of patients with MDs. More robust data on the correlation of CMR findings to clinical outcomes are required to establish the role and strengthen the position of CMR in the diagnostic algorithm and therapeutic management of MDs. CMR advantages, limitations and ways to overcome limiting factors in patients with MDs. •regional or global wall motion abnormalities •myocardial deformation (myocardial strain analysis) •focal or diffuse myocardial fibrosis •fatty infiltration of the myocardium •myocardial oedema •regional or global wall motion abnormalities •myocardial deformation (myocardial strain analysis) •focal or diffuse myocardial fibrosis •fatty infiltration of the myocardium •myocardial oedema CMR: cardiac magnetic resonance; eGFR: estimated glomerular filtration rate; ICD: implantable cardioverter defibrillator; LGE: late gadolinium enhancement; LV: left ventricular; MD: muscular dystrophy; MR: magnetic resonance; RV: right ventricular. CMR advantages, limitations and ways to overcome limiting factors in patients with MDs. •regional or global wall motion abnormalities •myocardial deformation (myocardial strain analysis) •focal or diffuse myocardial fibrosis •fatty infiltration of the myocardium •myocardial oedema •regional or global wall motion abnormalities •myocardial deformation (myocardial strain analysis) •focal or diffuse myocardial fibrosis •fatty infiltration of the myocardium •myocardial oedema CMR: cardiac magnetic resonance; eGFR: estimated glomerular filtration rate; ICD: implantable cardioverter defibrillator; LGE: late gadolinium enhancement; LV: left ventricular; MD: muscular dystrophy; MR: magnetic resonance; RV: right ventricular. The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The opinions expressed in this article are not necessarily those of the Editors of the European Journal of Preventive Cardiology or of the European Society of Cardiology. The author(s) received no financial support for the research, authorship, and/or publication of this article.