Effect of Bisoprolol on Progression of Aortic Stenosis (BLAST)

• Change in peak aortic jet velocity from baseline to 4 years follow-up [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  Change in peak aortic jet velocity from baseline to 4 years follow-up. For each patient, the change in peak aortic jet velocity is calculated as (peak aortic jet velocity at 4 year follow-up) − (peak aortic jet velocity at baseline) on Doppler echocardiography.
  
  

• Change in mean pressure gradient across aortic valve [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  Change in mean pressure gradient across aortic valve from baseline to 4 years follow-up
  
  
• Change in aortic valve area [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  Change in aortic valve area from baseline to 4 years follow-up
  
  
• Change in BNP levels [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  Change in BNP levels from baseline to 4 years follow-up
  
  
• Change in E/E' ratio [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  Change in the ratio of E velocity (early mitral inflow velocity) to E' velocity (early mitral annular velocity) from baseline to 4 years follow-up
  
  

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.