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Phenotypic Expression, Natural History, and Risk Stratification of Cardiomyopathy Caused by Filamin C Truncating
Marta Gigli1, Davide Stolfo1,2, Sharon L Graw3
1Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy (M.G., D.S., M.M., M.D.F., A.P., G.D.A., F.B., G.S.).
Circulation
|September 30, 2021
Summary
Filamin C truncating variants (FLNCtv) cause arrhythmogenic cardiomyopathy. This study reveals FLNCtv carriers face high risks of heart failure and arrhythmias, irrespective of left ventricular dysfunction severity.
Area of Science:
- Cardiology
- Genetics
- Molecular Biology
Background:
- Filamin C truncating variants (FLNCtv) are linked to arrhythmogenic cardiomyopathy.
- The presentation, natural history, and risk stratification of FLNCtv remain under-explored.
Purpose of the Study:
- To develop a risk profile for refractory heart failure and life-threatening arrhythmias in FLNCtv carriers.
- To analyze outcomes in a multicenter cohort of FLNCtv carriers.
Main Methods:
- Identified FLNCtv carriers from 10 tertiary care centers.
- Compiled clinical and outcome data, defining composite outcomes including mortality, heart transplantation, and ventricular assist device implantation.
- Compared prognoses with LMNA and DSP-related arrhythmogenic cardiomyopathy cohorts.
Main Results:
- Eighty-five FLNCtv carriers (42±15 years, 53% male) presented with heterogeneous phenotypes, including dilated and arrhythmogenic cardiomyopathies.
- During a median 61-month follow-up, 22% experienced mortality/heart transplantation/LVAD, 15% nonarrhythmic death/HT/LVAD, and 27% sudden cardiac death/major ventricular arrhythmias.
- FLNCtv carriers showed similar sudden cardiac death/major ventricular arrhythmias incidence compared to LMNA and DSP carriers; left ventricular ejection fraction predicted D/HT/LVAD risk.
Conclusions:
- FLNCtv arrhythmogenic cardiomyopathy is phenotypically diverse in tertiary referral patients.
- FLNCtv carriers face a significant risk of life-threatening arrhythmias.
- Arrhythmia risk in FLNCtv cardiomyopathy does not appear directly correlated with left ventricular dysfunction severity.
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