Phenotypic Expression, Natural History and Risk Stratification of Cardiomyopathy Caused by Filamin C Truncating Variants. Circulation Gigli, M., Stolfo, D., Graw, S., Merlo, M., Gregorio, C., Chen, S. N., Dal Ferro, M., Paldino, A., De Angelis, G., Brun, F., Jirikowic, J., Salcedo, E. E., Turja, S., Fatkin, D., Johnson, R., van Tintelen, J. P., Te Riele, A. S., Wilde, A., Lakdawala, N. K., Picard, K., Miani, D., Muser, D., Severini, G. M., Calkins, H., James, C. A., Murray, B., Tichnell, C., Parikh, V. N., Ashley, E. A., Reuter, C., Song, J., Judge, D., McKenna, W. J., Taylor, M. R., Sinagra, G., Mestroni, L. 2021


Background: Filamin C truncating variants (FLNCtv) cause a form of arrhythmogenic cardiomyopathy (ACM): the mode of presentation, natural history and risk stratification of FLNCtv remain incompletely explored. We sought to develop a risk profile for refractory heart failure and life-threatening arrhythmias in a multicenter cohort of FLNCtv carriers. Methods: FLNCtv carriers were identified from ten tertiary care centers for genetic cardiomyopathies. Clinical and outcome data were compiled. Composite outcomes were all-cause mortality/heart transplantation/left ventricle assist device (D/HT/LVAD), non-arrhythmic death/HT/LVAD and SCD/major ventricular arrhythmias (SCD/MVA). Previously established cohorts of 46 patients with LMNA and 60 with DSP-related ACM were used for prognostic comparison. Results: Eighty-five patients carrying FLNCtv were included (42±15 years, 53% males, 45% probands). Phenotypes were heterogeneous at presentation: 49% dilated cardiomyopathy, 25% arrhythmogenic left dominant cardiomyopathy, 3% arrhythmogenic right ventricular cardiomyopathy. Left ventricular ejection fraction (LVEF) was <50% in 64% of carriers and 34% had right ventricular fractional area changes (RVFAC=(right ventricular end-diastolic area - right ventricular end-systolic area)/ right ventricular end-diastolic area) <35%. During follow-up (median time 61 months), 19 (22%) carriers experienced D/HT/LVAD, 13 (15%) non-arrhythmic death/HT/LVAD and 23 (27%) SCD/MVA. The SCD/MVA incidence of FLNCtv carriers did not significantly differ from LMNA carriers and DSP carriers. In FLNCtv carriers, LVEF was associated with the risk of D/HT/LVAD and non-arrhythmic death/HT/LVAD. CConclusions: Among patients referred to tertiary referral centers, FLNCtv ACM is phenotypically heterogeneous and characterized by high risk of life-threatening arrhythmias, which does not seem to be associated with the severity of LV dysfunction.

View details for DOI 10.1161/CIRCULATIONAHA.121.053521

View details for PubMedID 34587765