Redefining genotype-phenotype correlation among patients with arrhythmogenic cardiomyopathy: a CMR cohort study

Abstract Background and purpose Arrhythmogenic cardiomyopathy (ACM) is a poorly defined, life-threatening condition. We aimed at identifying the patterns of regional wall motion abnormalities, fibrosis, and fatty infiltration seen on Cardiac Magnetic Resonance (CMR) and correlate them with the different genetic backgrounds. Methods We retrospectively identified ACM patients who underwent CMR and genetic test analysis. We collected data on CMR-derived cardiac volumes, function and tissue characterization. Results Seventy-eight patients with a clinical diagnosis of ACM were enrolled. Genetic tests were performed in 65 (83%) and identified a pathogenetic/likely pathogenetic variant in 51 (78%) patients (38% plakophilin-2, 23% desmoplakin, 5% desmoglein, 5% desmocollin and 8% filamin-C). Imaging features varied according to the genetic background, with subepicardial or mid-wall fibrosis distribution affecting predominantly the lateral and inferior segments of the left ventricle (LV) among the different groups and the septal segments in patients with the filamin-C variant. A characteristic LV subepicardial circumferential LGE pattern ("ring-like") was distinctively and almost exclusively associated with the desmoplakin variant. Conclusions Genetic variants of ACM present some common but also distinctive CMR phenotypes that can help in further characterizing the specific disease signatures associated with different genes. Further studies should investigate the prognostic value of these CMR findings.