Arrhythmic risk stratification of filamin C truncating variants carriers

Abstract Background Truncating variants in Filamin C (FLNCtv) are a rare cause of cardiomyopathy with heterogeneous phenotypic presentation and high incidence of life-threatening ventricular arrhythmias, including sudden cardiac death (SCD). Nevertheless, there is a residual gap in the definition of...

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Bibliographic Details
Published in:European heart journal 2023-11, Vol.44 (Supplement_2)
Main Authors: Gigli, M, Stolfo, D, Barbati, G, Sinagra, G, Mestroni, L
Format: Article
Language:English
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Summary:Abstract Background Truncating variants in Filamin C (FLNCtv) are a rare cause of cardiomyopathy with heterogeneous phenotypic presentation and high incidence of life-threatening ventricular arrhythmias, including sudden cardiac death (SCD). Nevertheless, there is a residual gap in the definition of solid risk markers for the stratification of arrhythmic risk and the significance of conventional predictors (i.e. left ventricular ejection fraction [LVEF]) remains extremely controversial. Purpose The aim of this study was to analyze the risk profile and to identify the factors associated with increased risk of life-threatening arrhythmias in an international multicenter cohort of FLNCtv carriers. Methods Patients were retrospectively collected from 19 international tertiary care centers for genetic cardiomyopathies. Primary endpoint was SCD/major ventricular arrhythmias (MVA, i.e. sustained ventricular tachycardia and appropriate implantable cardioverter defibrillator [ICD] shocks). Multivariate Cox regression analysis was performed to identify the predictors of SCD/MVA, taking into account non-sudden cardiac death/heart transplant/destination left ventricle assist device as competing event and including family clusters in the model as clustering factor. Results Among the 326 included carriers (median age 45 years, IQR 33-57; 51% males), 120 (37%) were probands. 100 (31%) carriers had no clinical signs of overt disease; for the others, phenotypic presentation was heterogeneous (36% dilated cardiomyopathy, 17% arrhythmogenic left dominant cardiomyopathy, 4% arrhythmogenic right or biventricular cardiomyopathy, 11% minor phenotype). Median LVEF was 51% (IQR 35%-59%, 41% had LVEF
ISSN:0195-668X
1522-9645
DOI:10.1093/eurheartj/ehad655.643