P539 - Case-control study of cardiovascular outcome of Loeys-Dietz versus Marfan syndrome

Background: Pathogenic variants in TGFBR1, TGFBR2 and SMAD3 genes cause Loeys-Dietz syndrome, and pathogenic variants in FBN1 cause Marfan syndrome. Despite similar phenotypes, both syndromes may have different cardiovascular outcomes.
Methods: Three expert centers performed a case-control study to compare cardiovascular outcomes. The Loeys-Dietz group comprised 43 men, 40 women with a mean age of 34±18 years. Thirty-two individuals had pathogenic variants in TGFBR1, 34 in TGFBR2, and 17 in SMAD3. The control group comprised 83 age and sex-frequency matched individuals with Marfan syndrome and FBN1 pathogenic variants.
Results: In Loeys-Dietz compared to Marfan syndrome, a patent ductus arteriosus (P=.014) was more prevalent, craniofacial score points were higher (P<.001), systemic score points lower (P<.001), and mitral valve prolapse less frequent (P=.003). Mean survival of Loeys-Dietz and Marfan syndrome was similar (75±3 versus 73±2 years; P=.811). Cardiovascular outcome was comparable between Loeys-Dietz and Marfan syndrome, including mean freedom from proximal aortic surgery (53±4 versus 48±3 years; P=.589), distal aortic repair (72±3 versus 67±2 years; P=.777), mitral valve surgery (75±4 versus 65±3 years; P=.108), and reintervention (20±3 versus 14±2 years; P=.112). In Loeys-Dietz syndrome, lower age at initial presentation predicted proximal aortic surgery (HR=.731; P<.001), where receiver operating characteristic analysis identified <=33.5 years with increased risk. Higher systemic score points (HR=1.205; P=.028) and increased aortic sinus diameters (HR=6.502; P=.001) were additional predictors of proximal aortic surgery in Loeys-Dietz syndrome. Conclusions: Cardiovascular outcome of Loeys-Dietz was comparable to Marfan syndrome, but the severity of systemic manifestations is a predictor of proximal aortic surgery.