Phenotypic Expression, Natural History, and Risk Stratification of Cardiomyopathy Caused by Filamin C Truncating Variants. Issue 20 (16th November 2021)

• Record Type: Journal Article
• Authors: Gigli, Marta; Stolfo, Davide; Graw, Sharon L.; Merlo, Marco; Gregorio, Caterina; Nee Chen, Suet; Dal Ferro, Matteo; PaldinoMD, Alessia; De Angelis, Giulia; Brun, Francesca; Jirikowic, Jean; Salcedo, Ernesto E.; Turja, Sylvia; Fatkin, Diane; Johnson, Renee; van Tintelen, J. Peter; Te Riele, Anneline S.J.M.; Wilde, Arthur A.M.; Lakdawala, Neal K.; Picard, Kermshlise; Miani, Daniela; Muser, Daniele; Maria Severini, Giovanni; Calkins, Hugh; James, Cynthia A.; Murray, Brittney; Tichnell, Crystal; Parikh, Victoria N.; Ashley, Euan A.; Reuter, Chloe; Song, Jiangping; Judge, Daniel P.; McKenna, William J.; Taylor, Matthew R.G.; Sinagra, Gianfranco; Mestroni, Luisa;
• Is Part Of: Circulation. Volume 144:Issue 20(2021)
• Publication Date: 2021-11-16
• Subjects: arrhythmogenic right ventricular dysplasia -- death, sudden, cardiac -- FLNC protein, human -- heart failure -- outcome studies -- prognosis; Blood -- Circulation -- Periodicals; Cardiovascular system -- Periodicals; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; 616.1
• DOI: 10.1161/CIRCULATIONAHA.121.053521
• Languages: English
• ISSNs: 0009-7322

Abstract

Abstract : Background: Filamin C truncating variants ( FLNCtv ) cause a form of arrhythmogenic cardiomyopathy: the mode of presentation, natural history, and risk stratification of FLNCtv remain incompletely explored. We aimed 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 10 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), nonarrhythmic death/HT/LVAD, and sudden cardiac death/major ventricular arrhythmias. Previously established cohorts of 46 patients with LMNA and 60 with DSP -related arrhythmogenic cardiomyopathies were used for prognostic comparison. Results: Eighty-five patients carrying FLNCtv were included (42±15 years, 53% men, 45% probands). Phenotypes were heterogeneous at presentation: 49% dilated cardiomyopathy, 25% arrhythmogenic left dominant cardiomyopathy, 3% arrhythmogenic right ventricular cardiomyopathy. Left ventricular ejection fraction 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%) experienced nonarrhythmic death/HT/LVAD, and 23 (27%) experienced sudden cardiac death/major ventricular arrhythmias. The sudden cardiac death/major ventricular arrhythmias incidence of FLNCtv carriers did not significantly differ from LMNA carriers and DSP carriers. In FLNCtv carriers, left ventricular ejection fraction was associated with the risk of D/HT/LVAD and nonarrhythmic death/HT/LVAD. Conclusions: Among patients referred to tertiary referral centers, FLNCtv arrhythmogenic cardiomyopathy is phenotypically heterogeneous and characterized by a high risk of life-threatening arrhythmias, which does not seem to be associated with the severity of left ventricular dysfunction. Abstract : Supplemental Digital Content is available in the text.