Abstract 17361: Phenotype of the Aortic Valve in Patients With Filamin-A Mutations: Echocardiographic Features and Clinical Outcomes

Abstract

Background: Filamin-A ( FLNA ) mutations have been associated with the development of mitral valve prolapse and a unique mitral valve features described as a paradoxical restrictive leaflets motion in diastole has been recently described using a comprehensive echocardiographic screening. Polyvalvular diseases have also been reported in these patients, especially affecting the aortic valve. Objectifs: The objective of this study was to perform a comprehensive echocardiographic analysis of the aortic valve (AV) and the proximal aortic root of patients with FLNA mutations, and assess the impact of the aortic disease on outcomes. Methods: We included in this analysis 256 subjects (42±22 years, 136 men, 76 mutated: FLNA+) with confirmed genetic status, from 5 FLNA families. Comprehensive echocardiographic characterization of the aortic valve and the proximal aortic root, including the measurement of the aortic annulus, sinuses of Valsalva, sinotubular junction and ascending aorta, was performed in FLNA+ patients vs control relatives. Results: Overall, 47 subjects (18%) presented an aortic valve alteration: 40 (53%) of FLNA+ compared to 7 (4%) FLNA- subjects (p<0.001). Among the 76 FLNA+ patients, 7 (9%) had a bicuspid aortic valve phenotype as opposed to 2 (1%) in control relatives (p=0.02). The underlying disease affecting the aortic valve was AV sclerosis, stenosis and AV regurgitation with either prolapse or restricted cusps motion. A restrictive opening of the AV was also reported in some patients. Aortic valve mean gradient was slightly increased in FLNA+ compared with FLNA- subjects (5.7±5.1 vs 4.2±1.8 mmHg, P= 0.02). In adults, left ventricular outflow tract diameter (12.5±1.4 vs 12.0±1.0 mm/m 2 ; p=0.02), sinuses of Valsalva (17.8±2.5 vs 16.2±1.9 mm/m 2 ; p<0.001) and sinotubular junction (15.0±2.0 vs 13.7±1.6 mm/m 2 ; p<0.001) were larger in FLNA+ subjects as compared to control relatives. 8 FLNA+ subjects (11%; 6 males) underwent aortic valve-related surgery versus 0 in controls (p<0.001). Survival was also impaired in FLNA+ male subjects (70 year old: 72% vs 64%, p=0.03). Conclusion: The FLNA -mutated patients presented aortic valve disease more frequently, including a higher prevalence of bicuspid valve, stenosis, and regurgitation owing to either cusp prolapsed or restrictive motion. This unique features described in this population was associated with worse clinical outcomes, especially in FLNA+ males. Management and decision making should be done according to the features of these patients with polyvalvular diseases