Abstract 11897: Cardiovascular Phenotype of the Recently Discovered Aggressive Aneurysms-Osteoarthritis Syndrome (aos) Caused by Smad3 Mutations
Background Aneurysms-osteoarthritis syndrome (AOS), caused by SMAD3 mutations, is a recently described autosomal dominant syndrome characterized by arterial tortuosity and aneurysms throughout the arterial tree in combination with osteoarthritis. This is the first study describing all cardiovascular findings.
Methods and results We included 44 AOS patients (age 42±17 years) participating in extensive cardiovascular evaluation, including transthoracic echocardiography and computed tomography angiography. In 68% of patients, arterial aneurysms were present, predominantly (87%) in the aortic root. In 11% multiple aneurysms were found and 46% showed arterial tortuosity throughout thorax and abdomen. In addition, in 38% intracranial aneurysms were found and 50% of patients showed intracranial tortuosity. Mortality was high (34%) with a median survival with elective surgery of 62 years (Figure). Main cause of death was aortic dissection (60%), which already happened at mildly dilated aortic diameters (mean Sinus of Valsalva diameter 43.2 ± 4.3 mm). Median age at first elective cardiovascular surgery or intervention, for example valve-sparing aortic root replacement or splenic artery coiling, was 41 years (Figure). Furthermore, intracardiac abnormalities were common, such as congenital heart defects (9%), mitral valve abnormalities (68%), left ventricular hypertrophy (23%) and atrial fibrillation (22%). NT-proBNP was significantly increased in AOS patients compared to matched controls (p<0.001).
Conclusion In conclusion, SMAD3 mutations predispose patients to aggressive and widespread cardiovascular disease. If left untreated, mortality is high. Dissections can occur at relatively small aortic diameters, so aggressive and early elective repair of the ascending aorta should be considered once the diameter reaches 40 mm.
- © 2011 by American Heart Association, Inc.