Author + information
- Received June 9, 2019
- Revision received November 21, 2019
- Accepted December 21, 2019
- Published online February 24, 2020.
- Olivier Milleron, MDa,
- Florence Arnoult, MDa,b,
- Gabriel Delorme, MDa,
- Delphine Detaint, MDa,
- Quentin Pellenc, MDc,
- Richard Raffoul, MDd,
- Maria Tchitchinadze, MDa,
- Maud Langeois, BScia,
- Celine Guien, BScie,
- Christophe Beroud, PhDe,
- Jacques Ropers, PhDf,
- Nadine Hanna, MD, PhDg,h,
- Pauline Arnaud, PharmDg,h,i,
- Laurent Gouya, MD, PhDa,i,
- Catherine Boileau, PharmD, PhDa,g,h,i and
- Guillaume Jondeau, MD, PhDa,h,i,∗ (, )@hopitalbichat
- aCentre de référence pour le syndrome de Marfan et apparentés, VASCERN HTAD European Reference Center, AP-HP, Hôpital Bichat, Paris, France
- bService des explorations fonctionnelles AP-HP, Hôpital Bichat, Paris, France
- cService de chirurgie vasculaire AP-HP, Hôpital Bichat, Paris, France
- dService de chirurgie cardiaque AP-HP, Hôpital Bichat, Paris, France
- eAix Marseille Université, INSERM, MMG, Bioinformatics & Genetics, Marseille, France
- fUnité De Recherche Clinique, AP-HP, Pitié Salpêtrière–Charles Foix, Paris, France
- gDépartement de génétique moléculaire AP-HP, Hôpital Bichat, Paris, France
- hINSERM U1148, LVTS, Hôpital Bichat, Paris, France
- iUniversité de Paris, Paris, France
- ↵∗Address for correspondence:
Dr. Guillaume Jondeau, Centre de Référence pour le Syndrome de Marfan et apparentés, Hôpital Bichat, 46 rue Henri Huchard, 75018 Paris, France.
Background Aortic risk has not been evaluated in patients with Marfan syndrome and documented pathogenic variants in the FBN1 gene.
Objectives This study sought to describe aortic risk in a population with Marfan syndrome with pathogenic variants in the FBN1 gene as a function of aortic root diameter.
Methods Patients carrying an FBN1 pathogenic variant who visited our reference center at least twice were included, provided they had not undergone aortic surgery or had an aortic dissection before their first visit. Aortic events (aortic surgery or aortic dissection) and deaths were evaluated during the 2 years following each patient visit. The risk was calculated as the number of events divided by the number of years of follow-up.
Results A total of 954 patients were included (54% women; mean age 23 years). During follow-up (9.1 years), 142 patients underwent prophylactic aortic root surgery, 5 experienced type A aortic dissection, and 12 died (noncardiovascular causes in 3, unknown etiology in 3, post-operative in 6). When aortic root diameter was <50 mm, risk for proven type A dissection (0.4 events/1,000 patient-years) and risk for possible aortic dissection (proven aortic dissection plus death of unknown cause, 0.7 events/1,000 patients-years) remained low in this population that was treated according to guidelines. Three type A aortic dissections occurred in this population during the 8,594 years of follow-up, including 1 in a patient with a tubular aortic diameter of 50 mm, but none in patients with a family history of aortic dissection. The risk for type B aortic dissection in the same population was 0.5 events/1,000 patient-years.
Conclusions In patients with FBN1 pathogenic variants who receive beta-blocker therapy and who limit strenuous exercise, aortic risk remains low when maximal aortic diameter is <50 mm. The risk of type B aortic dissection is close to the remaining risk of type A aortic dissection in this population, which underlines the global aortic risk.
This study was supported by the Fondation Cœur et Recherche, Paris, France, Fédération Française de Cardiologie, Paris, France, ANR-14-CE15-0012, Paris, France, CRCBD18119, Paris, France. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received June 9, 2019.
- Revision received November 21, 2019.
- Accepted December 21, 2019.
- 2020 American College of Cardiology Foundation
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