Effects of Losartan Versus Atenolol on Aortic and Cardiac Muscle Stiffness in Adults With Marfan Syndrome
Effects of Losartan Versus Atenolol on Aortic and Cardiac Muscle Stiffness in Adults With Marfan Syndrome
Marfan syndrome is an inherited connective tissue disorder with morbidity and mortality from
 aortic dilation and dissection. The degree of aortic dilation and response to beta-blockade
 (standard of care) vary in adults with Marfan syndrome. However, aortic stiffness is often
 present, and can be a predictor of aortic dilation and cardiovascular complications. In
 addition, adults with Marfan syndrome develop left ventricular diastolic dysfunction, which
 can progress to heart failure. Aortic stiffness and diastolic dysfunction are important and
 logical therapeutic targets in adults with Marfan syndrome.

 TGF-beta mediates disease pathogenesis in Marfan syndrome and contributes to aortic
 stiffness. The angiotensin receptor blocker, losartan, inhibits TGF-beta activity and
 reverses aortic wall pathology in a Marfan mouse model. Losartan also decreases aortic
 stiffness and improves diastolic function in hypertension, renal disease and hypertrophic
 cardiomyopathy.

 This trial is a randomized, double-blind trial of 50 adults with Marfan syndrome, treated
 with 6 months of atenolol vs. losartan. Arterial tonometry for aortic stiffness and
 echocardiography for diastolic function will be performed at the beginning and end of
 treatment. A blood draw for serum markers of extracellular matrix turnover and inflammation
 will also be performed at 0 and 6 months. We plan to determine whether losartan decreases
 aortic stiffness and left ventricular diastolic dysfunction significantly more than atenolol.
Please See Summary.
Inclusion Criteria:

 -  Age greater than 25 years

 -  Clinical Marfan Syndrome

 Exclusion Criteria:

 -  Previous aortic or cardiac surgery

 -  Pregnancy

 -  Renal Insufficiency

 -  Medication intolerance