Filamin A heart valve disease as a genetic cause of inherited bicuspid and tricuspid aortic valve disease

Abstract

ObjectiveVariants in theFLNAgene have been associated with mitral valve dystrophy (MVD), and even polyvalvular disease has been reported. This study aimed to analyse the aortic valve and root involvement inFLNA-MVD families and its impact on outcomes.Methods262 subjects (37 (18–53) years, 140 male, 79 carriers:FLNA+) from 4FLNA-MVD families were included. Echocardiography was performed in 185 patients and histological analysis in 3 explanted aortic valves. The outcomes were defined as aortic valve surgery or all-cause mortality.ResultsAortic valve alterations were found in 58% ofFLNA+ compared with 6% ofFLNA− (p<0.001). 9 (13.4%)FLNA+ had bicuspid aortic valve compared with 4 (3.4%)FLNA− (p=0.03). Overall, the transvalvular mean gradient was slightly increased inFLNA+ (4.8 (4.1–6.1) vs 4.0 (2.9–4.9) mm Hg, p=0.02). The sinuses of Valsalva and sinotubular junction diameters were enlarged inFLNA+ subjects (all p<0.05). 8FLNA+ patients underwent aortic valve surgery (0 in relatives; p<0.001). Myxomatous remodelling with an infiltration of immune cells was observed. Overall survival was similar betweenFLNA+versusFLNA− subjects (86±5% vs 85±6%, p=0.36). There was no statistical evidence for an interaction between genetic status and sex (p=0.15), but the survival tended to be impaired inFLNA+ men (p=0.06) whereas not in women (p=0.71).ConclusionThe patients withFLNAvariants present frequent aortic valve disease and worse outcomes. Bicuspid aortic valve is more frequent in patients carrying theFLNA-MVD variants. These unique features should be factored into the management of patients with dystrophic and/or bicuspid aortic valve.