New insights into the correlation between genotype and cardiac phenotype in laminopathies

Abstract Funding Acknowledgements Type of funding sources: None. Background Genotype-phenotype correlation and risk stratification for heart failure progression in patients with cardiolaminopathies are poorly defined. Purpose The primary aim the present study is to characterize correlate phenotype genotype sex. secondary test two main existing prognostic scores (the Arbustini Whabi score), both developed predict ventricular arrhythmic events cardiolaminopathies, major arrhythmias (MVA) end-stage (ESHF). Methods This a retrospective, single-center study, including lamin (LMNA) and/or emerin (EMD) genetic variants. Data were collected from first medical contact (FMC) last follow-up (FU). Results 28 (57% male, 82% probands, 68% family history sudden death) included: 96% harbored LMNA heterozygous variants, 15% had non-missense 11% variant previously never described. Functionally, 50% undetermined significance (VUS, C3), rest either pathogenetic or likely pathogenic (C4/C5) Median age at FMC was 41 years (IQR 30-55 years), median FU 11 8-18 years). At FMC, all cardiac involvement, 54% muscle involvement. By FU, atrial fibrillation, 43% atrioventricular block (AVB) > I degree, carried an implantable cardioverter defibrillator (21% resynchronization), suffered least one episode MVA, 25% ESHF: died due refractory HF, 14% underwent transplantation (mean 43.5 ± 9 onset different types not influenced by penetrance (AV) conduction defects (Figure 1 Panel A) tachyarrhythmias B) higher earlier subjects Subjects VUS, compared those pathogenetic/likely showed significantly lower later MVA 2 non- sustained tachycardia (NSVT, Figure 2, B), but AV disturbances, arrhythmias, contractile dysfunction. score proved be predictor ESHF, while only predicted MVA. Conclusions In our series, prevalence appearance phenotypes sex, presence VUS correlated other manifestations disfunction failure. Our data suggest importance close monitoring larger prospective studies even VUS. All sever 60.