PO-05-158 DESCRIBING THE PHENOTYPE OF THE FLMC GENE TO INCLUDE SEPTAL SCARRING

Abstract

Filamin C (FLNC) gene variants have been reported to be associated with arrhythmogenic cardiomyopathy (ACM), dilated cardiomyopathy (DCM), and sudden cardiac death. Currently left ejection fraction and sudden cardiac death risks do not appear to be clearly associated. FLNC and DSP + cardiomyopathy tend to show ring-shaped sub-epicardial scars. Although there is evidence to suggest FLNC variants can cause arrhythmia or sudden cardiac arrest, it continues to be reported as a variant of uncertain significance. The primary objective was to further describe the phenotype of FLNC gene variants to include the presence of cardiac septal scarring. A retrospective review was completed of patients with known FLNC gene variants using the Phoenix Cardiac Genetic Registry (PCGR) database. The PCGR includes patients that have undergone cardiomyopathy and arrhythmia genetic testing due to clinical abnormalities including reduced left ventricular ejection fraction, cardiac scarring on baseline imaging, and/or arrhythmia. Left ventricular ejection fraction, cardiac arrhythmia, and cardiac scarring locations were compared to further describe the FLNC phenotype. The PCGR database included 115 patients with cardiomyopathy and arrhythmia genetic testing completed between 2015 and 2022 ranging from 25 to 77 years of age. Of these patients, 10 patients came back with an FLNC variant. The mean LVEF was 31% (+/- SD 14.0). Ventricular arrhythmia history was reported in 9 patients, 6 of which had PVC or VT ablations. Atrial arrhythmia history was reported in 8 patients, 7 of which required ablations. Cardiac magnetic resonance imaging (CMRI) was completed in 6 out of the 10 patients revealing septal scarring in 4 patients. Variants of unknown significance in the FLNC gene are associated with septal substrate abnormalities, suggesting that the majority of patients with VT may be pathogenic.