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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
PubMed

Insights

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.
Abstract

Keywords:
FLNC protein, humanarrhythmogenic right ventricular dysplasiadeath, sudden, cardiacheart failureoutcome studiesprognosis

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