Imaging signatures of high-risk arrhythmogenic genotypes in dilated cardiomyopathy.
BACKGROUND Dilated cardiomyopathy (DCM) exhibits substantial genotypic heterogeneity, paralleled by diverse cardiac magnetic resonance (CMR) phenotypes and clinical presentations. However, the specific genotype-phenotype associations underlying this heterogeneity remain incompletely clear. METHODS Ninety DCM patients were prospectively enrolled and stratified into three subtypes: high-risk arrhythmogenic variant carriers (HRAv, n = 30), TTN truncating variant carriers (TTNtv, n = 30), and genotype-negative patients (GN, n = 30). High-risk arrhythmogenic variants were identified as DSP, FLNC, LMNA, and PLN variants. Comprehensive CMR parameter comparisons and logistic regression analyses were performed to identify the associations between genotypes and CMR features. RESULTS Among 90 participants (mean age, 46 years; 54 men), no significant differences were observed in ventricular volumes, systolic functions or LV strain among subtypes. HRAv patients presented with a higher prevalence of LGE (83%) compared with TTNtv (13%) and GN (40%) (p < 0.001), with typical linear midwall, ring-like, and subepicardial patterns. Global native T1 mapping(1379 vs. 1329 vs. 1335 ms, p = 0.037), T2 mapping (46.3 vs. 44.1 vs. 42.8 ms, p < 0.001), and extracellular volume (ECV)(35.8 vs. 31.3 vs. 30.5%, p < 0.001) were significantly elevated in HRAv compared with TTNtv and GN. In Firth penalized logistic regression models, higher global T2 (odds ratio[OR] = 1.22, 95%CI: 1.06-1.43, p = 0.004), higher global ECV(OR = 1.45, 95%CI: 1.17-1.86, p < 0.001), and LGE presence(OR = 9.22, 95%CI: 3.26-29.81, p < 0.001) were independently associated with HRAv status when separately added to the baseline model. CONCLUSION Compared with TTNtv and genotype-negative DCM, HRAv is characterized by a distinct CMR tissue phenotype marked by more extensive myocardial injury and fibrosis, despite similar ventricular remodeling and systolic impairment. These findings suggest that CMR tissue characterization may help identify genotype-associated phenotypic differences in DCM.