Cardiovascular involvement and outcomes in Marfan syndrome: new observations on evolving aortic risk associations in a single-center cohort from Poland

INTRODUCTION: Marfan syndrome (MFS) is a connective tissue disorder with aortic dilatation driving morbidity and mortality. OBJECTIVES: To characterize cardiovascular profile, outcomes, and factors associated with the lifetime risk of thoracic aortic events (TAE) in a contemporary MFS cohort. Patients and methods: We retrospectively analyzed data from MFS patients diagnosed based on revised Ghent criteria and followed for a median 6.8 (IQR 3-10) years at our tertiary center. RESULTS: The cohort comprised 151 patients (104 probands, median age 32 years, 58% female). Aortic root involvement was present in 95% patients, a positive family history in 69%, a systemic score of ≥7 points in 61%, and ectopia lentis in 36%. Among patients with identified FBN1 variants, 60% carried dominant-negative and 40% haploinsufficiency variants, 27% variants were novel. Overall, 107 TAE occurred in 85 (56%) patients. The first TAE (median age 33 years) comprised 60 elective operations and 25 aortic dissections; 19 in previously undiagnosed individuals. TAE-free survival was shorter in men and in patients with high systemic score, mainly before age 35, whereas later haploinsufficiency variants were associated with TAE. A second TAE developed in 18 (21%) patients and was more frequent after dissection than elective surgery (HR 2.9, 95% CI 1.2-7.1, P = 0.01). Mitral valve surgery was performed in 13% of patients. CONCLUSIONS: The majority of MFS patients experienced a TAE. The association of TAE risk with factors, such as male gender, extra-aortic features, and FBN1 variant type, varies with age group.