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. 2022 Feb;19(2):235-243.
doi: 10.1016/j.hrthm.2021.09.029. Epub 2021 Oct 1.

Filamin-C variant-associated cardiomyopathy: A pooled analysis of individual patient data to evaluate the clinical profile and risk of sudden cardiac death

Rudy Celeghin  1 , Alberto Cipriani  1 , Riccardo Bariani  1 , Maria Bueno Marinas  1 , Marco Cason  1 , Michela Bevilacqua  2 , Monica De Gaspari  1 , Stefania Rizzo  1 , Ilaria Rigato  1 , Stefano Da Pozzo  3 , Alessandro Zorzi  1 , Martina Perazzolo Marra  1 , Gaetano Thiene  1 , Sabino Iliceto  1 , Cristina Basso  4 , Domenico Corrado  1 , Kalliopi Pilichou  1 , Barbara Bauce  1
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Free article

Filamin-C variant-associated cardiomyopathy: A pooled analysis of individual patient data to evaluate the clinical profile and risk of sudden cardiac death

Rudy Celeghin et al. Heart Rhythm. 2022 Feb.
Free article

Abstract

Background: Mutations in filamin-C (FLNC) are involved in the pathogenesis of arrhythmogenic cardiomyopathy (ACM) and dilated cardiomyopathy (DCM), and have been associated with a left ventricular (LV) phenotype, characterized by nonischemic LV fibrosis, ventricular arrhythmias, and sudden cardiac death (SCD).

Objective: The purpose of this study was to investigate the prevalence of FLNC variants in a gene-negative ACM population and to evaluate the clinical phenotype and SCD risk factors in FLNC-associated cardiomyopathies.

Methods: ACM probands who tested negative for mutations in ACM-related genes underwent FLNC genetic screening. Clinical and genetic data were collected and pooled together with those of previously published FLNC-ACM and FLNC-DCM patients.

Results: In a cohort of 270 gene-elusive ACM probands, 12 (4.4%) had FLNC variants, and 13 additional family members carried the same mutation. Eighteen FLNC variant carriers (72%) had a diagnosis of ACM (72% male; mean age 45 years). On pooled analysis, 145 patients with FLNC-associated cardiomyopathies were included. Electrocardiographic (ECG) low QRS voltages were detected in 37%, and T-wave inversion (TWI) in inferolateral/lateral leads in 24%. Among 67 patients who had cardiac magnetic resonance (CMR), LV nonischemic late gadolinium enhancement (LGE) was found in 75%. SCD occurred in 28 patients (19%), 15 of whom showed LV nonischemic LGE/fibrosis. Compared with patients with no SCD, those who experienced SCD more frequently had inferolateral/lateral TWI (P = .013) and LV LGE/fibrosis (P = .033).

Conclusion: Clinical phenotype of FLNC cardiomyopathies is characterized by late-onset presentation and typical ECG and CMR features. SCD is associated with the presence of LV LGE/fibrosis but not with severe LV systolic dysfunction.

Keywords: Arrhythmogenic cardiomyopathy; Cardiac magnetic resonance; Dilated cardiomyopathy; Filamin-C; Sudden cardiac death.

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