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FBN1 Genetic Variation and Aortic Dissection in Marfan Syndrome
Study Questions:
What is the risk of aortic events as a function of aortic root diameter among patients with Marfan syndrome and pathogenic variants in the FBN1 gene?
Methods:
In a single-center, retrospective study, data from patients with an FBN1 pathogenic variant who were seen at least twice at a reference center were evaluated, excluding patients who had 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. Aortic 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; median age, 19 years [interquartile range, 0-83 years]). During follow-up (median 9.1 [2.0-19.8] years), 142 patients underwent prophylactic aortic root surgery, five experienced type A aortic dissection, and 12 died (noncardiovascular causes in three, unknown etiology in three, postoperative in six). When aortic root diameter was <50 mm, the risk for proven type A dissection (0.4 events/1,000 patient-years) and the 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 patient-years of follow-up, including one 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:
Among patients with FBN1 pathogenic variants who are treated with beta-blocker therapy and who limit strenuous exercise, aortic risk remains low when the maximal aortic diameter is <50 mm. The risk of type B aortic dissection is close to the risk of type A aortic dissection, which the authors concluded is a sign of the underlying global aortic risk in this population.
Perspective:
Multiple variants in the FBN1 gene, associated with the large protein fibrillin-1, are found in a subset of patients with Marfan syndrome. Although aortic root dimension is used as the dominant factor to estimate the risk of aortic complications and guide the timing of prophylactic surgery among patients with Marfan syndrome, early disease recognition (aided by familial genetic screening) can play an important role in attempting to modify risk through exercise limitations and the prescription of beta-adrenergic antagonists. This study, performed at a French referral center that routinely employs family genetic screening, found that, with guideline-directed treatment, there was a relatively low rate of aortic complications among patients with Marfan syndrome and an FBN1 gene pathologic variant. These findings help support the use of existing guideline recommendations for patients with Marfan syndrome and a pathogenic variant in the FBN1 gene.
Clinical Topics: Cardiac Surgery, Congenital Heart Disease and Pediatric Cardiology, Geriatric Cardiology, Invasive Cardiovascular Angiography and Intervention, Prevention, Vascular Medicine, Cardiac Surgery and Arrhythmias, Cardiac Surgery and CHD and Pediatrics, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Interventions, CHD and Pediatrics and Quality Improvement, Interventions and Structural Heart Disease, Interventions and Vascular Medicine
Keywords: Adrenergic beta-Antagonists, Aneurysm, Dissecting, Aorta, Cardiac Surgical Procedures, Dissection, Genetic Testing, Genetic Variation, Geriatrics, Heart Defects, Congenital, Marfan Syndrome, Risk, Secondary Prevention, Vascular Diseases
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