To assess the efficacy of angiotensin II receptor blocker, Losartan, to prevent progressive dilation of aortic root in patients with Marfan syndrome.

Marfan syndrome (MFS) is a multisystem connective tissue disorder of autosomal dominant inheritance1. The cardinal features are noted in the cardiovascular, ocular, and skeletal system. The most life-threatening complication of MFS is progressive aortic root dilation leading to aortic dissection or rupture. Losartan, an angiotensin II type I receptor (AT1) antagonist, is a drug already in clinical use for hypertension and type II diabetic nephropathy. A recent study showed that Losartan prevents aortic root dilation and lung problem in a mouse model of MFS. Therefore, the goals of this clinical trial are to examine the efficacy and safety of Losartan in patients with Marfan syndrome for aortic root dilation prevention.

• Drug: Losartan and Atenolol or Propranolol
• Drug: Atenolol or Propranolol

• Experimental: In combination therapy,the maximal dose of Losartan is 100 mg/day for adult and 50 mg/day for children. 50 mg of Atenolol once daily, 20 mg of Propranolol twice daily for adult and 1 mg/Kg/day for children
• Active Comparator: The maximal dose of Atenolol or Propranolol is 150 mg/day for adult and 2 mg/Kg/day for children.

Inclusion criteria

• Marfan syndrome with recognized aortic root dilation
• Patients must be older than one year of age
• Beta-blocker treatment at least three months
• Must sign an informed consent form

Exclusion criteria

• Prior to aortic root surgery
• Aortic root dimension more than 5.5cm
• Aortic surgery within 6 months
• Diabetes mellitus or liver and renal dysfunction or asthma
• Pregnancy
• Intolerance to Losartan therapy