Case-matched Comparison of Cardiovascular Outcome in Loeys-Dietz Syndrome versus Marfan Syndrome.

Pathogenic variants in , and genes cause Loeys-Dietz syndrome, and pathogenic variants in cause Marfan syndrome. Despite their similar phenotypes, both syndromes may have different cardiovascular outcomes. Three expert centers performed a case-matched comparison of cardiovascular outcomes. The Loeys-Dietz group comprised 43 men and 40 women with a mean age of 34 ± 18 years. Twenty-six individuals had pathogenic variants in , 40 in , and 17 in . For case-matched comparison we used 83 age and sex-frequency matched individuals with Marfan syndrome. In Loeys-Dietz compared to Marfan syndrome, a patent ductus arteriosus ( = 0.014) was more prevalent, the craniofacial score was higher ( < 0.001), the systemic score lower ( < 0.001), and mitral valve prolapse less frequent ( = 0.003). Mean survival for Loeys-Dietz and Marfan syndrome was similar (75 ± 3 versus 73 ± 2 years; = 0.811). Cardiovascular outcome was comparable between Loeys-Dietz and Marfan syndrome, including mean freedom from proximal aortic surgery (53 ± 4 versus 48 ± 3 years; = 0.589), distal aortic repair (72 ± 3 versus 67 ± 2 years; = 0.777), mitral valve surgery (75 ± 4 versus 65 ± 3 years; = 0.108), and reintervention (20 ± 3 versus 14 ± 2 years; = 0.112). In Loeys-Dietz syndrome, lower age at initial presentation predicted proximal aortic surgery (HR = 0.748; < 0.001), where receiver operating characteristic analysis identified ≤33.5 years with increased risk. In addition, increased aortic sinus diameters (HR = 6.502; = 0.001), and higher systemic score points at least marginally (HR = 1.175; = 0.065) related to proximal aortic surgery in Loeys-Dietz syndrome. Cardiovascular outcome of Loeys-Dietz syndrome was comparable to Marfan syndrome, but the severity of systemic manifestations was a predictor of proximal aortic surgery.