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.