Influence of sex on cardiovascular outcomes in RBM20 variant carriers. (3rd October 2022)

• Record Type: Journal Article
• Authors: Cannie, D; Protonotarios, A; Syrris, P; Sengupta, A; Bilinska, Z; Arana Achaga, X; Barriales-Villa, R; Garcia-Pavia, P; Gimeno, J; Merlo, M; Wahbi, K; Fatkin, D; Mogensen, J; Rasmussen, T B; Elliott, P
• Is Part Of: European heart journal. Volume 43(2022)Supplement 2
• Publication Date: 2022-10-03
• Subjects: Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/ehac544.1744
• Languages: English
• ISSNs: 0195-668X

Abstract

Abstract: Background: Variants in the RBM20 gene cause dilated cardiomyopathy and may be associated with a poor prognosis. Objectives: To determine disease penetrance, the risk of adverse events and the influence of sex on outcomes in RBM20 variant carriers. Methods: Consecutive probands and relatives carrying pathogenic or likely pathogenic RBM20 variants were retrospectively recruited from 12 cardiomyopathy units. The primary endpoint was a composite of malignant ventricular arrhythmia (MVA) and end-stage heart failure (ESHF). MVA and ESHF endpoints were also analysed separately and males and females compared. Results: Longitudinal follow-up data were available for 163 RBM20 variant carriers (82 male, median age 36.5 years, median follow-up 77.6 months). 10/163 had an MVA event at baseline. 30/153 without baseline MVA (19.6%) reached the primary endpoint with a trend towards worse outcomes in males (p=0.08). 16/153 (10.5%) had new MVA with no difference between males and females (p=0.92). 20/163 (12.2%) developed ESHF (17 males and 3 females; p<0.001). By the end of follow-up, 114 patients (70%) had either left ventricular systolic dysfunction (LVSD) or had experienced MVA. 22 patients received a first diagnosis of LVSD during follow-up. Disease penetrance in individuals over 40 years of age was 78.5% by last evaluation. Eleven patients that reached the MVA endpoint had a left ventricular ejection fraction (LVEF) available within 6 months of the event. Median [IQR] contemporary LVEF was 30% [23.75, 40%]. 5/11 patients had a contemporary LVEF >35%. 1/11 had a contemporary LVEF >45% (a female, 1st degree relative presenting with sustained ventricular tachycardia and an LVEF of 65%). Conclusions: RBM20 variants are highly penetrant. The risk of MVA in male and female RBM20 variant carriers is similar but male sex is strongly associated with ESHF. MVA events occur in patients with LVEF >35%. Funding Acknowledgement: Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Clinical Research Training Fellowship