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Pathogenic FBN1 Genetic Variation and Aortic Dissection in Patients With Marfan Syndrome
Olivier Milleron1, Florence Arnoult2, Gabriel Delorme1
1Centre de référence pour le syndrome de Marfan et apparentés, VASCERN HTAD European Reference Center, AP-HP, Hôpital Bichat, 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.
Insights
Aortic dissection risk is low in Marfan syndrome patients with FBN1 variants and aortic root diameter <50 mm, especially with beta-blocker therapy and limited exercise. This highlights the importance of monitoring global aortic risk.
Area of Science:
- Cardiovascular Genetics
- Marfan Syndrome Research
- Aortic Disease
Background:
- Aortic risk assessment is crucial for Marfan syndrome patients with FBN1 gene variants.
- Previous evaluations of aortic risk in this specific population are limited.
Purpose of the Study:
- To describe the aortic risk in individuals with Marfan syndrome and FBN1 pathogenic variants.
- To analyze aortic risk as a function of aortic root diameter.
Main Methods:
- Included 954 patients with FBN1 variants, followed for 9.1 years.
- Monitored aortic events (surgery, dissection) and deaths post-visit.
- Calculated event rates per 1,000 patient-years.
Main Results:
- Aortic dissection risk was low (<0.7 events/1,000 patient-years) when aortic root diameter was <50 mm.
- Prophylactic surgery was performed on 142 patients; 5 had type A dissection.
- Type B dissection risk was 0.5 events/1,000 patient-years.
Conclusions:
- Aortic risk remains low in FBN1 variant patients with aortic diameter <50 mm, on beta-blockers, and limiting exercise.
- Global aortic risk, including type B dissection, is comparable to residual type A dissection risk.
- Management strategies should consider the overall aortic risk profile.
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