Effect of Bisoprolol on Progression of Aortic Stenosis
Effect of Bisoprolol on Progression of Aortic Stenosis
Aortic stenosis has been thought to be a degenerative process basically induced by
 long-lasting mechanical stress, and hemodynamic factors such as shear forces, acceleration of
 blood flow, hypertension and rapid heart rate might contribute to progression of aortic
 stenosis. Peak aortic jet velocity is known to be associated with clinical outcomes in mild
 and moderate AS, and our previous study showed that rate of progression was significantly
 associated with baseline aortic jet velocity in mild aortic stenosis. Because beta-blocker
 therapy would decrease aortic jet velocity and heart rate, it might decrease hemodynamic
 stress and eventually slow down the degenerative process in patients whose disease is not too
 advanced for therapy to be effective. The investigators hypothesized that a beta-blocker
 therapy would decrease the rate of progression of aortic stenosis by modifying hemodynamic
 factors favorably in patients with mild to moderate aortic stenosis.
Aortic stenosis (AS) is a gradually progressive disease, characterized by an increase in
 calcium deposition leading to progressive narrowing of the aortic valve (AV). There are
 currently no effective medical treatment to halt the disease process and surgical valve
 replacement remains the only proven therapy when the valve becomes severely stenotic. AS is
 mediated by a chronic inflammatory disease process, very similar to that seen in
 atherosclerosis, but lipid-lowering therapy did not slow the progression of AS in the
 SALTIRE, SEAS, or ASTRONOMER trials. It is possible that these trials may have targeted
 patients in whom disease was too advanced for lipid-lowering therapy to be effective, or in
 whom atherosclerotic mechanism was not the central pathogenic process in AS. Because
 identifying and treating patients in earlier stages of AS would not be cost-effective, it
 seems more logical to explore alternative pharmacological approaches.

 AS has been thought to be a degenerative process basically induced by long-lasting mechanical
 stress, and hemodynamic factors such as shear forces, acceleration of blood flow,
 hypertension and rapid heart rate might contribute to progression of AS. Peak aortic jet
 velocity is known to be associated with clinical outcomes in mild and moderate AS, and our
 previous study showed that rate of progression was significantly associated with baseline
 aortic jet velocity in mild AS. Because beta-blocker therapy would decrease aortic jet
 velocity and heart rate, it might decrease hemodynamic stress and eventually slow down the
 degenerative process in patients whose disease is not too advanced for therapy to be
 effective. In a retrospective, observational study, beta-blocker therapy was associated with
 a favorable clinical outcome in AS.

 The investigators hypothesized that bisoprolol, a new generation beta-blocker, would decrease
 the rate of progression of AS by modifying hemodynamic factors favorably in patients with
 mild to moderate AS.
Inclusion Criteria:

 -  Mild to moderate aortic stenosis defined by peak velocity of aortic jet between 2.0
 and 3.5 m/sec

 -  Untreated hypertension: systolic BP ≥ 140 or diastolic BP ≥ 90 mmHg Treated
 hypertension using dihydropiridine calcium channel blockers, ACE inhibitors, ARB or
 diuretics

 -  Patients received no beta-blocker therapy for more than 12 months

 Exclusion Criteria:

 -  Symtomatic aortic stenosis: presence of exertional dyspnea, angina or syncope

 -  Planned cardiac surgery (e.g., CABG, valve repair or replacement, or aneurysmectomy)
 or planned major non-cardiac surgery within the study period

 -  Stroke or resuscitated sudden death in the past 6 months

 -  Evidence of congestive heart failure, or left ventricular ejection fraction < 50%

 -  Significant renal disease manifested by serum creatinine > 2.0mg/dL

 -  History of intolerance to beta-blocker

 -  History of adult asthma manifested by bronchospasm in the past 6 months, or currently
 taking regular anti-asthmatic medication(s)

 -  Moderate or severe aortic regurgitation

 -  Atrial fibrillation

 -  Female of child-bearing potential who do not use adequate contraception and women who
 are pregnant or breast-feeding

 -  A diagnosis of cancer (other than superficial squamous or basal cell skin cancer) in
 the past 3 years or current treatment for the active cancer

 -  Any clinically significant abnormality identified at the screening visit, physical
 examination, laboratory tests, or electrocardiogram which, in the judgment of the
 Investigator, would preclude safe completion of the study

 -  Unwillingness or inability to comply with the procedures described in this protocol