Late diagnosis of Marfan syndrome is associated with unplanned aortic surgery and cardiovascular death

Background: Marfan syndrome (MFS) guidelines recommend optimal pharmacologic therapy (OPT) and replacement of the ascending aorta (RAA) at 5.0 cm in diameter to prevent acute type A aortic dissection (ATAAD) and death. The effect of early MFS diagnosis and initiation of therapy on outcomes is not known. Therefore, we sought to evaluate the effect of age at MFS diagnosis and therapy initiation on delayed RAA and death. 

Methods: This retrospective observational cohort study with long-term follow-up included consecutive patients with MFS, pathogenic FBN1 variant, and regular visits to a European Reference Network Center. We considered MFS diagnosis at age ≥21 years late and OPT initiation at age <21 years early. Outcomes were delayed RAA with aneurysm diameter >5.0 cm or ATAAD and death from all causes. We used landmark design starting at age 21 years to determine associations with outcomes. 

Results: The study group consisted of 288 patients (45.1% male), including 169 patients with late diagnosis of MFS (58.7%) and 63 with early OPT (21.9%). During mean follow-up of 25 ± 14.7 years, 78 patients had delayed RAA, with 42 operations for ATAAD and 36 for aneurysms ≥5.0 cm. There were 33 deaths, including 11 deaths late after ATAAD. All deaths were cardiovascular. Late diagnosis, but not early OPT, showed univariate association with delayed RAA (P < .001) and death (P = .025). Multivariate Cox regression analysis confirmed late diagnosis as predictor of delayed RAA (hazard ratio, 8.01; 95% confidence interval, 2.52-25.45; P < .001) and death (hazard ratio, 4.68; 95% confidence interval, 1.17-18.80; P = .029). 

Conclusions: Late diagnosis of MFS is associated with delayed surgery and death.