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

Abstract

BackgroundMarfan syndrome (MFS) guidelines recommend optimal pharmacological therapy (OPT) and replacement of the ascending aorta (RAA) at 5.0cm diameters 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. ObjectiveTo evaluate the effect of age at MFS diagnosis and therapy initiation on delayed RAA and death. MethodsThis 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 >5.0cm or ATAAD, and death from all causes. We used landmark design starting at age 21 years to determine associations with outcomes. ResultsThe study group consisted of 288 patients (45.1% male), including 169 patients with late MFS diagnosis (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 ≥5.0cm. 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<0.001) and death (P=0.025). Multivariate Cox regression analysis confirmed late diagnosis as predictor of delayed RAA (hazard ratio (HR)=8.01; 95% confidence interval (95%CI) 2.52-25.45; P<0.001) and death (HR=4.68; 95%CI 1.17-18.80; P=0.029). ConclusionsLate diagnosis of Marfan syndrome is associated with delayed surgery and death.