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Original research
Filamin A heart valve disease as a genetic cause of inherited bicuspid and tricuspid aortic valve disease
  1. Constance Delwarde1,
  2. Claire Toquet1,
  3. Anne Sophie Boureau1,
  4. Robin Le Ruz1,
  5. Solena Le Scouarnec1,
  6. Jean Mérot1,
  7. Florence Kyndt1,
  8. Daniel Bernstein2,
  9. Jonathan A Bernstein2,
  10. Jan J J Aalberts3,
  11. Hervé Le Marec1,
  12. Jean-Jacques Schott1,
  13. Jean-Christian Roussel1,
  14. Thierry Le Tourneau1,
  15. Romain Capoulade1
  1. 1 Nantes Université, CHU Nantes, CNRS, INSERM, l’institut du thorax, F-44000 Nantes, Nantes, France
  2. 2 Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA
  3. 3 Department of Cardiology, Reinier de Graaf Hospital, Delft, Netherlands
  1. Correspondence to Dr Romain Capoulade, Institut du thorax, Nantes, Pays de la Loire, France; romain.capoulade{at}; Dr Thierry Le Tourneau; Thierry.LETOURNEAU{at}


Objective Variants in the FLNA gene 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 in FLNA-MVD families and its impact on outcomes.

Methods 262 subjects (37 (18–53) years, 140 male, 79 carriers: FLNA+) from 4 FLNA-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.

Results Aortic valve alterations were found in 58% of FLNA+ compared with 6% of FLNA− (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 in FLNA+ (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 in FLNA+ subjects (all p<0.05). 8 FLNA+ 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 between FLNA+ versus FLNA− 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 in FLNA+ men (p=0.06) whereas not in women (p=0.71).

Conclusion The patients with FLNA variants present frequent aortic valve disease and worse outcomes. Bicuspid aortic valve is more frequent in patients carrying the FLNA-MVD variants. These unique features should be factored into the management of patients with dystrophic and/or bicuspid aortic valve.

  • Bicuspid aortic valve
  • Aortic Valve Insufficiency
  • Aortic Valve Stenosis
  • Congenital Abnormalities

Data availability statement

Data are available upon reasonable request.

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  • CD and CT are joint first authors.

  • TLT and RC are joint senior authors.

  • X @asboureau, @CapouladeR

  • Contributors RC and TLT designed the study. All authors participated to the familial enrolment and the collection of the genetic, clinical, imaging, histological and surgical data. CD, CT, TLT and RC analysed and interpreted the data. CD and RC drafted the manuscript. RC and TLT approved the final version and are responsible for the overall content. All authors critically reviewed the manuscript and contributed to editing the final version.

  • Funding The present study has received funding from the Fédération Française de Cardiologie (2011, Paris, France) and the French Ministry of Health ‘PHRC-I 2012’ (API12/N/019, Paris, France) awarded to TLT. This work has also received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 846291 and the French Society of Cardiology under the “Alain Castaigne” scientific prize, both awarded to RC. RC is also supported by a “Connect Talent” research chair from Région Pays de la Loire and Nantes Métropole.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.