TY - JOUR T1 - Genotype–phenotype correlation in arrhythmogenic right ventricular cardiomyopathy—risk of arrhythmias and heart failure JF - Journal of Medical Genetics JO - J Med Genet SP - 858 LP - 864 DO - 10.1136/jmedgenet-2021-107911 VL - 59 IS - 9 AU - Alex Hørby Christensen AU - Pyotr G Platonov AU - Henrik Kjærulf Jensen AU - Monica Chivulescu AU - Anneli Svensson AU - Pia Dahlberg AU - Trine Madsen AU - Tanja Charlotte Frederiksen AU - Tiina Heliö AU - Øyvind Haugen Lie AU - Kristina H Haugaa AU - Jesper Hastrup Svendsen AU - Henning Bundgaard Y1 - 2022/09/01 UR - http://jmg.bmj.com/content/59/9/858.abstract N2 - Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is predominantly caused by desmosomal genetic variants, and clinical hallmarks include arrhythmias and systolic dysfunction. We aimed at studying the impact of the implicated gene(s) on the disease course.Methods The Nordic ARVC Registry holds data on a multinational cohort of ARVC families. The effects of genotype on electrocardiographic features, imaging findings and clinical events were analysed.Results We evaluated 419 patients (55% men), with a mean follow-up of 11.2±7.4 years. A pathogenic desmosomal variant was identified in 62% of the 230 families: PKP2 in 41%, DSG2 in 13%, DSP in 7% and DSC2 in 3%. Reduced left ventricular ejection fraction (LVEF) ≤45% on cardiac MRI was more frequent among patients with DSC2/DSG2/DSP than PKP2 ARVC (27% vs 4%, p<0.01). In contrast, in Cox regression modelling of patients with definite ARVC, we found a higher risk of arrhythmias among PKP2 than DSC2/DSG2/DSP carriers: HR 0.25 (0.10–0.68, p<0.01) for atrial fibrillation/flutter, HR 0.67 (0.44–1.0, p=0.06) for ventricular arrhythmias and HR 0.63 (0.42–0.95, p<0.05) for any arrhythmia. Gene-negative patients had an intermediate risk (16%) of LVEF ≤45% and a risk of the combined arrhythmic endpoint comparable with DSC2/DSG2/DSP carriers. Male sex was a risk factor for both arrhythmias and reduced LVEF across all genotype groups (p<0.01).Conclusion In this large cohort of ARVC families with long-term follow-up, we found PKP2 genotype to be more arrhythmic than DSC2/DSG2/DSP or gene-negative carrier status, whereas reduced LVEF was mostly seen among DSC2/DSG2/DSP carriers. Male sex was associated with a more severe phenotype.The full data set cannot be made available due to patient confidentiality. The data cannot be made publicly available due to patient confidentiality. ER -