BACKGROUND: Duchenne muscular dystrophy (DMD) patients are monitored periodically for cardiac involvement, including cardiac MRI with gadolinium-based contrast agents (GBCA). Texture analysis (TA) offers an alternative approach to assess late gadolinium enhancement (LGE) without relying on GBCA administration, impacting DMD patients' care. The study aimed to evaluate the prognostic value of selected TA features in the LGE assessment of DMD patients. RESULTS: We developed a pipeline to extract TA features of native T1 parametric mapping and evaluated their prognostic value in assessing LGE in DMD patients. For this evaluation, five independent TA features were selected using Boruta to identify relevant features based on their importance, least absolute shrinkage and selection operator (LASSO) to reduce the number of features, and hierarchical clustering to target multicollinearity and identify independent features. Afterward, logistic regression was used to determine the features with better discrimination ability. The independent feature inverse difference moment normalized (IDMN), which measures the pixel values homogeneity in the myocardium, achieved the highest accuracy in classifying LGE (0.857 (0.572-0.982)) and also was significantly associated with changes in the likelihood of LGE in a subgroup of patients with three yearly examinations (estimate: 23.35 (8.7), p-value = 0.008). Data are presented as mean (SD) or median (IQR) for normally and non-normally distributed continuous variables and numbers (percentages) for categorical ones. Variables were compared with the Welch t-test, Wilcoxon rank-sum, and Chi-square tests. A P-value < 0.05 was considered statistically significant. CONCLUSION: IDMN leverages the information native T1 parametric mapping provides, as it can detect changes in the pixel values of LGE images of DMD patients that may reflect myocardial alterations, serving as a supporting tool to reduce GBCA use in their cardiac MRI examinations.

• Klíčová slova
• Cardiac MRI, Duchenne muscular dystrophy, Radiomics, Texture analysis,
• MeSH
• dítě MeSH
• Duchennova muskulární dystrofie * diagnostické zobrazování   MeSH
• gadolinium MeSH
• kontrastní látky MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   MeSH
• mladiství MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• gadolinium MeSH
• kontrastní látky MeSH

Duchenne muscular dystrophy is a genetic disorder where an X-linked mutation in the DMD gene initiates pathogenic development caused by the absence of dystrophin protein. This impacts primarily the evolution of a functional muscle tissue resulting in muscle weakness and later severe disability in young male patients leading to an early death. Patients in the final stage develop dilated cardiomyopathy leading ultimately to cardiac or respiratory failure as the cause of death. This review discusses recent advances in modeling the DMD pathology in vitro. It describes in detail the molecular abnormalities found on the cellular and organoid levels. The in vitro pathology is compared to that found in patients. Likewise, the drawbacks and limitations of current models are discussed.

• Klíčová slova
• Cardiomyocyte, Contraction, Duchenne muscular dystrophy, Heart failure, In vitro modeling,
• MeSH
• dilatační kardiomyopatie patologie   MeSH
• Duchennova muskulární dystrofie patologie   MeSH
• lidé MeSH
• srdce fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND: Duchenne muscular dystrophy (DMD) manifests in males mainly by skeletal muscle impairment, but also by cardiac dysfunction. The assessment of the early phases of cardiac involvement using echocardiography is often very difficult to perform in these patients. The aim of the study was to use cardiac magnetic resonance (CMR) strain analysis and mitral annular plane systolic excursion (MAPSE) in the detection of early left ventricular (LV) dysfunction in DMD patients. METHODS AND RESULTS: In total, 51 male DMD patients and 18 matched controls were examined by CMR. MAPSE measurement and functional analysis using feature tracking (FT) were performed. Three groups of patients were evaluated: A/ patients with LGE and LV EF < 50% (n = 8), B/ patients with LGE and LVEF ≥ 50% (n = 13), and C/ patients without LGE and LVEF ≥ 50% (n = 30). MAPSE and global LV strains of the 3 DMD groups were compared to controls (n = 18). Groups A and B had significantly reduced values of MAPSE, global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) in comparison to controls (p < 0.05). The values of MAPSE (11.6 ± 1.9 v 13.7 ± 2.7 mm) and GCS (- 26.2 ± 4.2 v - 30.0 ± 5.1%) were significantly reduced in group C compared to the controls (p < 0.05). CONCLUSION: DMD patients had decreased LV systolic function measured by MAPSE and global LV strain even in the case of normal LV EF and the absence of LGE. FT and MAPSE measurement provide sensitive assessment of early cardiac involvement in DMD patients.

• Klíčová slova
• Cardiac magnetic resonance, Duchenne muscular dystrophy, Feature tracking, Strain analysis,
• MeSH
• Duchennova muskulární dystrofie * diagnostické zobrazování   MeSH
• dysfunkce levé srdeční komory * diagnostické zobrazování   MeSH
• funkce levé komory srdeční MeSH
• kardiomyopatie * MeSH
• lidé MeSH
• myokard MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Duchenne muscular dystrophy (DMD) is a severe genetic disorder characterized by the lack of functional dystrophin. DMD is associated with progressive dilated cardiomyopathy, eventually leading to heart failure as the main cause of death in DMD patients. Although several molecular mechanisms leading to the DMD cardiomyocyte (DMD-CM) death were described, mostly in mouse model, no suitable human CM model was until recently available together with proper clarification of the DMD-CM phenotype and delay in cardiac symptoms manifestation. We obtained several independent dystrophin-deficient human pluripotent stem cell (hPSC) lines from DMD patients and CRISPR/Cas9-generated DMD gene mutation. We differentiated DMD-hPSC into cardiac cells (CC) creating a human DMD-CC disease model. We observed that mutation-carrying cells were less prone to differentiate into CCs. DMD-CCs demonstrated an enhanced cell death rate in time. Furthermore, ion channel expression was altered in terms of potassium (Kir2.1 overexpression) and calcium handling (dihydropyridine receptor overexpression). DMD-CCs exhibited increased time of calcium transient rising compared to aged-matched control, suggesting mishandling of calcium release. We observed mechanical impairment (hypocontractility), bradycardia, increased heart rate variability, and blunted β-adrenergic response connected with remodeling of β-adrenergic receptors expression in DMD-CCs. Overall, these results indicated that our DMD-CC models are functionally affected by dystrophin-deficiency associated and recapitulate functional defects and cardiac wasting observed in the disease. It offers an accurate tool to study human cardiomyopathy progression and test therapies in vitro.

• Klíčová slova
• DMD, adrenergic response, cardiomyocyte death, cardiomyocytes, duchenne muscular dystrophy, excitation-contraction coupling, human pluripotent stem cells, intracellular calcium,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The progressive cardiomyopathy that develops in boys with Duchenne and Becker muscular dystrophy (DMD/BMD) is presumed to be a secondary consequence of the fibrosis within the myocardium. There are only limited data on using parametric imaging in these patients. The purpose of this study was to assess native T1 and extracellular volume (ECV) values in DMD patients. METHODS: The Czech population of males with DMD/BMD was screened. All eligible patients fulfilling the inclusion criteria were included. Forty nine males underwent cardiac magnetic resonance (MR) examination including T1 native and post-contrast mapping measurements. One DMD patient and all BMD patients were excluded from statistical analysis. Three groups were compared - Group D1 - DMD patients without late gadolinium enhancement (LGE) (n = 23), Group D2 - DMD patients with LGE (n = 20), and Group C - gender matched controls (n = 13). RESULTS: Compared to controls, both DMD groups had prolonged T1 native relaxation time. These results are concordant in all 6 segments as well as in global values (1041 ± 31 ms and 1043 ± 37 ms vs. 983 ± 15 ms, both p < 0.05). Group D2 had significantly increased global ECV (0.28 ± 0.044 vs. 0.243 ± 0.013, p < 0.05) and segmental ECV in inferolateral and anterolateral segments in comparison with controls. The results were also significant after adjustment for subjects' age. CONCLUSION: DMD males had increased native T1 relaxation time independent of the presence or absence of myocardial fibrosis. Cardiac MR may provide clinically useful information even without contrast media administration.

• Klíčová slova
• Cardiac magnetic resonance, Cardiomyopathy, Duchene muscular dystrophy, T1 mapping; extracellular volume,
• MeSH
• Duchennova muskulární dystrofie diagnostické zobrazování   MeSH
• gadolinium analýza   MeSH
• kardiomyopatie diagnostické zobrazování   MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mladiství MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• gadolinium MeSH