Differential Trajectories of CMR Strain Parameters in Muscular Dystrophy: Age and Genotype-Specific Analysis

Background: Cardiac involvement is a leading cause of mortality in patients with Duchenne (DMD) and Becker muscular dystrophy (BMD). Conventional metrics like ejection fraction lack sensitivity for early dysfunction. While CMR strain imaging shows promise, the age and genotype-specific trajectories of segmental and global strain parameters across the dystrophinopathy spectrum remain poorly characterized. This study aim to comprehensively analyze the progression patterns of regional and global circumferential (CS), radial (RS), and longitudinal strain (LS) in DMD and BMD patients compared to healthy controls, and to investigate the association between strain impairment and dystrophin gene mutation location in DMD.

Methods: This retrospective study included patients with genetically confirmed DMD (n=397) and BMD(n=49) (aged 5-20 years), and 125 age matched healthy male controls. All underwent CMR at 3T. Totally 1007 CMR scans of DMD and 101 scans of BMD were enrolled in analysis. Global and segmental (basal, mid, apical) strain parameters (GLS, BLS, MLS, ALS; GCS, BCS, MCS, ACS; GRS, BRS, MRS, ARS) were analyzed using feature-tracking (cvi42). Patients were stratified by age group (5-7y, 7-10y, 10-14y, 14-20y) and DMD patients by mutation location (exons 1-30, 31-44, 45-79). Age-specific Z-scores were calculated from controls. Piecewise linear regression and linear mixed-effects models were employed to analyze trajectories and group differences.

Results: Significantly different strain trajectories were observed between DMD, BMD, and controls. DMD patients showed the earliest and most severe impairment, with mean Z-scores diverging from healthy values by age 7-10, particularly in LS and RS (-2 to -4 SD). BMD patients demonstrated intermediate, slower progression. DMD patients with mutations in exons 1-30 showed more pronounced strain impairment compared to other mutations. Comprehensive genotype-specific analysis revealed distinct patterns of myocardial strain impairment across different mutation locations in the dystrophin gene. This group showed progressive deterioration across all longitudinal parameters (GLS, BLS, MLS, ALS), with Z-scores ranging from -3.6 to -1.2. The Exons 31-44 group exhibited moderate CMR strain impairment (Z-scores: -2.7 to -0.1), while the Exons 45-79 group showed the mildest CMR strain involvement (Z-scores: -0.9 to -0.4).

Conclusion: CMR strain parameters, especially segmental analysis, effectively track differential cardiac dysfunction in dystrophinopathies, with DMD showing a rapid, age-dependent decline and BMD a more gradual change. Strain impairment is associated with genotype in DMD. These findings underscore the value of dynamic CMR strain as a sensitive biomarker for early detection, progression monitoring and disease stractification in these populations.

Different strain trajectories of DMD, BMD and controls.
Age specific strain impairment
Genotype specific analysis