Beta Blockers and Angiotensin Receptor Blockers in Bicuspid Aortic Valve Disease Aortopathy (BAV Study)
Beta Blockers and Angiotensin Receptor Blockers in Bicuspid Aortic Valve Disease Aortopathy (BAV Study)
The purpose of this study is to determine whether long-term treatment with a beta-blocker
 (BB) such as atenolol and/or an angiotensin receptor blocker (ARB) such as telmisartan, given
 to adult patients with bicuspid aortic valve (BAV) disease (aortopathy) reduces the widening
 (dilatation) of the aorta from its baseline size.
Bicuspid aortic valve (BAV) is the most common congenital heart disease lesion with an
 estimated 280 000 to 560 000 people affected in the Canada. Dilatation of the ascending aorta
 is a common feature in patients with BAV and is a result of inherent vascular abnormalities
 with superimposed effects of age and acquired cardiovascular risk factors. Severe aortic
 dilatation (> 50mm) leads to aortic dissection and premature death.

 Histopathological studies of the aortas in patients with BAVs report similar findings to that
 of patients with Marfan syndrome. Beta Blocker (BB) therapy and more recently, Angiotensin
 Receptor Blocker (ARB) therapy, have been shown to decrease to rate of aortic dilatation and
 be of benefit to patients with Marfan syndrome. There is no such data however in patients
 with BAV and aortopathy.

 Within the context of a randomized clinical trial, the investigators proposed to test the
 hypothesis that BB or ARB will reduce the rate of progressive aortic dilatation in adults
 with BAVs and ascending aortopathy as compared to placebo.

 Design: Multicentre, randomized, double-blind, placebo-controlled, trial of adult patients
 with bicuspid aortic valve aortopathy. Patients who are eligible to take either study
 medication will be randomly allocated to participate in either the BB (atenolol) vs. placebo
 arm, or the ARB (telmisartan) vs. placebo arm. Patients who are ineligible for the BB arm
 will be assigned to the ARB vs. placebo arm and patients who are ineligible for the ARB arm
 will be assigned to the BB vs. placebo arm. Within each arm, all participants will be
 randomized to take either placebo or active medication. The atenolol arm will be up-titrated
 to100mg/day and the telmisartan arm will be up-titrated to 80 mg/day, or to the maximum
 tolerated dose.
Inclusion Criteria:

 -  Age => 18 years

 -  Men and women with BAV and ascending aorta measuring > 37mm.

 -  Written informed consent

 General Study Exclusion Criteria

 1. History of cardiac diseases, such as

 -  Symptomatic aortic stenosis or aortic regurgitation referred for surgical
 intervention or asymptomatic severe aortic stenosis or regurgitation based on
 current guidelines

 -  Uncontrolled heart failure, right ventricular failure due to pulmonary
 hypertension

 -  Cardiogenic shock

 2. Systolic blood pressure < 100 mmHg

 3. History of drug sensitivity, contraindication or adverse reaction to both BB and ARB.
 Participants who are able to tolerate only a BB will be allocated to the BB vs.
 placebo arm, and participants who are able to tolerate only an ARB will be allocated
 to the ARB vs. placebo arm, assuming no other exclusion criteria are met.

 4. Ascending aorta measuring ≥ 50mm, requiring prophylactic ascending aorta surgery

 5. Unable to provide informed consent

 6. Need for both BB and ARB for treatment of concomitant medical conditions for which
 there are no other alternatives. Participants who are taking an ARB which cannot be
 discontinued will be allocated to the BB arm, and participants who are taking a BB
 which cannot be discontinued will be allocated to the ARB arm, if no other exclusion
 criteria are met.

 7. Prior surgery on ascending aorta or aortic root (balloon valvuloplasty, aortic
 valvotomy or post coarctation surgery are acceptable)

 8. Women who are pregnant at screening visit

 9. Contraindication to MRI (claustrophobia, pacemaker, metallic clip in eye or brain)

 10. History of any illness which limits the participants' ability to complete the study

 Additional Exclusion Criteria for BB arm only

 1. Heart rate <60 bpm

 2. Heart block (1st, 2nd and 3rd degree AV block on ECG), or sick sinus syndrome

 3. Asthma of sufficient severity to represent a contraindication to BB use in the
 judgment of the patient's physician

 4. History of severe peripheral artery disorders

 5. History of pheochromocytoma without the use of alpha-adrenergic blockers

 6. History of metabolic acidosis

 Additional Exclusion Criteria for ARB arm only

 1. Women who are pregnant, lactating or who intend to become pregnant during the course
 of the study

 2. Women who are of childbearing age and are not on reliable, accepted form of birth
 control

 3. Hyperkalemia [serum potassium > 5.5 mmol/L] or renal dysfunction [GFR<45% measured by
 MDRD)

 4. Patients being treated with an ACE Inhibitor that cannot be discontinued. (These
 patients may be randomized in the BB arm if no exclusion criteria are met.)

 5. History of bilateral renal artery stenosis or unilateral renal artery stenosis to a
 solitary kidney

 6. History of hepatic insufficiency and hepato-biliary obstruction

 7. History of fructose intolerance