Comparison of Two Medications Aimed at Slowing Aortic Root Enlargement in Individuals With Marfan Syndrome--Pediatric Heart Network

Marfan syndrome is an inheritable disorder that affects the body's connective tissue. An
abnormal protein results in connective tissue that is weaker than normal. Because connective
tissue is found throughout the body, Marfan syndrome can affect many body systems, including
the skeleton, eyes, nervous system, skin, lungs, heart, and blood vessels. Overall, heart
and blood vessel abnormalities are the leading cause of death in individuals with Marfan
syndrome. A common blood vessel abnormality associated with this disease involves the aorta,
which is the large artery that carries blood away from the heart to the rest of the body.
The aortic root, the portion of the aorta that is attached to the heart, may enlarge and
tear or even rupture. A tear or rupture is considered a life-threatening emergency. Recent
studies have shown that the medication losartan may reduce aortic root growth and improve
heart function. The purpose of this study is to compare the effectiveness of losartan versus
atenolol at slowing aortic root growth in individuals with Marfan syndrome.

This 3-year study will enroll individuals with Marfan syndrome. Participants will be
randomly assigned to receive either losartan or atenolol on a daily basis. All participants
will initially receive a low dose of their assigned medication. This dose will be gradually
increased every 3 to 4 weeks until the maximum tolerated dose is reached. A continuous
electrocardiogram (ECG) that monitors heart rate and activity in 24-hour intervals will be
used to determine the proper dose increase for each participant. Participants will then
receive the maximum tolerated dose for the remainder of the study. Study visits will occur
at baseline and Months 6, 12, 24, and 36. Each study visit will include a physical
examination, a medical history review, an ECG, an echocardiogram, and questionnaires.
Additionally, at the baseline study visit blood will be collected for laboratory testing.