Pathogenic FBN1 Genetic Variation and Aortic Dissection in Patients With Marfan Syndrome.

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.