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Filamin C variant-associated Cardiomyopathy: A Pooled Analysis of Individual Patient Data to Evaluate the Clinical Profile and Risk of Sudden Cardiac Death
- Publication Year :
- 2022
- Publisher :
- Elsevier B.V., 2022.
-
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.
- Subjects :
- Proband
Adult
Male
Risk
medicine.medical_specialty
Adolescent
Cardiac magnetic resonance
Filamins
Population
Cardiomyopathy
Contrast Media
Magnetic Resonance Imaging, Cine
Sudden cardiac death
Electrocardiography
Fibrosis
Physiology (medical)
Internal medicine
medicine
Prevalence
Humans
cardiovascular diseases
FLNC
Filamin-C
education
Child
Arrhythmogenic Cardiomyopathy
Aged
education.field_of_study
Dilated Cardiomyopathy
business.industry
Dilated cardiomyopathy
Middle Aged
medicine.disease
Pedigree
Sudden Cardiac death
Death, Sudden, Cardiac
Phenotype
Cohort
Mutation
Cardiology
Female
Cardiology and Cardiovascular Medicine
business
Cardiomyopathies
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....0f8ef5e46382539dfe275f42bf5a22b5