ERS5735. Genotype-Phenotype Relationships in Arrhythmogenic Cardiomyopathy Using Cardiac MRI
Authors* Denotes Presenting Author
Farah Cadour *;
Toronto General Hospital, University Health Network, University of Toronto; University of Toronto
Sarin Lekchuensakul;
Toronto General Hospital, University Health Network, University of Toronto
Danna Spears;
Toronto General Hospital, University Health Network, University of Toronto
Melanie Care;
Toronto General Hospital, University Health Network, University of Toronto
Kate Hanneman;
Toronto General Hospital, University Health Network, University of Toronto; University of Toronto
Objective:
Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy that can involve both ventricles. Several genes have been identified as pathogenic in ACM. However, there is currently limited data on the association between cardiac MRI findings and specific genotypes in ACM.
Materials and Methods:
In this retrospective cohort study, consecutive adult patients with a pathogenic variant in a gene associated with ACM and at least one cardiac MRI between 2004 - 2023 were included. Cardiac MRI evaluation included quantification of left ventricular (LV) and right ventricular (RV) volumes and function, regional wall motion abnormalities, and late gadolinium enhancement (LGE).
Results:
Of the 225 included patients (110 women, mean age 40 ± 16 years), pathogenic variants in desmosomal genes were identified in 107 (48%) (most frequently plakophilin-2 PKP2 in 22% and desmoplakin DSP in 18%) and non-desmosomal genes in 118 (52%) (most frequently titin TTN in 27% and lamin A/C LMNA in 12%). The proportion of women was higher in the desmosomal group compared to the non-desmosomal group (61% vs 38%, <em>p</em> = 0.001), however there was no difference in age (40 ± 17 years vs 41 ± 15 years, <em>p</em> = 0.59). The presence of any RV abnormality (RV dilation, low RVEF, RV regional wall motion abnormality, or RV LGE) was identified in 50% and the prevalence did not differ between non-desmosomal and desmosomal groups (56% vs 43%, <em>p</em> = 0.06). However, the prevalence of any LV abnormality (LV dilation, low LVEF, LV regional wall motion abnormality, or LV LGE) and prevalence of bi-ventricular abnormalities were more frequent in the non-desmosomal group (74% vs 39%, <em>p</em> = 0.001 and 49% vs 25%, <em>p</em> < 0.001, respectively). RVEF and LVEF were significantly lower in the non-desmosomal group (43±13% vs 51 ± 9%, <em>p</em> < 0.001 and 42 ± 16% vs 56 ± 8%, <em>p</em> < 0.001, respectively). However, there was substantial variability in the non-desmosomal group with mean RVEF ranging from 40 ± 13% in those with TTN variants to 56 ± 8% in those with TMEM43 variants. LGE imaging was available in 154 patients and the prevalence of LV-LGE did not differ between groups (46% non-desmosomal vs 53% desmosomal, <em>p</em> = 0.40); however, a ring-like pattern of LGE was more frequent in the desmosomal group (37% vs 10%, <em>p</em> < 0.001).
Conclusion:
Patients with pathogenic variants in non-desmosomal ACM genes were more likely to have left and biventricular abnormalities and had more impaired biventricular function compared to those with variants in desmosomal genes. The overall prevalence of LV LGE was similar between groups; however, those with variants in desmosomal genes were more likely to have a ring-like pattern of LGE. Further study is needed to determine whether differences in cardiac MRI findings are associated with disease progression and future arrhythmic events.
