Effect of Beta Blockade on Left Ventricular Remodeling and Function in Moderate to Severe Asymptomatic Aortic Regurgitation
Condition: Aortic Valve Insufficiency
MeSH terms: Aortic Valve Insufficiency; Ventricular Remodeling
Study type: Interventional
Phase: Phase 4

Summary: 
      The primary objective of this study is to evaluate the effect of beta-blocker on left
      ventricular (LV) remodeling in asymptomatic patients with moderate to severe aortic
      regurgitation.
    

Detailed description: 
      The left ventricle responds to the volume load of chronic aortic regurgitation (AR) with a
      series of compensatory mechanisms, including an increase in end-diastolic volume, an increase
      in chamber compliance that accommodates the increased volume without an increase in filling
      pressures, and a combination of eccentric and concentric hypertrophy. The greater diastolic
      volume permits the ventricle to eject a large total stroke volume to maintain forward stroke
      volume in the normal range. This is accomplished through rearrangement of myocardial fibers
      with the addition of new sarcomeres and development of eccentric LV hypertrophy. As a
      consequence left ventricular ejection fraction will remain in the normal range.

      The clinical course of chronic aortic regurgitation is characterized by a prolonged phase of
      stability during which the left ventricle adapts to the volume overload. Eventually
      myocardial failure ensues through a series of complex events that include changes in myocyte
      phenotype due to re-expression of fetal genes, cellular apoptosis alteration in the
      expression and function of contractile proteins and changes in the extracellular matrix.

      The role of long-term vasodilator therapy in the care of asymptomatic patients with severe
      aortic regurgitation is controversial. Vasodilator therapy has been used to reduce the
      regurgitant volume, afterload, left ventricular volumes, and wall stress in an effort to
      preserve left ventricular function and reduce left ventricular mass. Thus time to surgical
      intervention has been found to be delayed by calcium antagonists, ACE-inhibitors and
      hydralazine, while a more recent study did not find any effect of nifedipine or enalapril on
      time to surgery or left ventricular volume and function.

      The decision to recommend operative intervention to the asymptomatic patient with chronic,
      severe aortic regurgitation (AR) is very difficult because aortic valve replacement (AVR)
      continues to entail immediate risk, and biologic and mechanical valves still have problems
      resulting in significant morbidity and mortality. On the other hand, the mortality rate in
      asymptomatic patients with AR is very low, and surgery does not improve the quality of life.
      Thus, the indication in asymptomatic patients must be delayed until changes occur that will
      predict an increased risk of operative or long-term death after AVR. At present indication
      for aortic valve replacement is development of symptoms, an increase in left ventricular
      volume or a decline in left ventricular function.
    

Intervention name(s): Metoprolol; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Patients with moderate to severe aortic valve insufficiency will be randomized to Metoprolol; Patients with moderate to severe aortic valve insufficiency will be randomized to Placebo
Intervention MeSH terms: Metoprolol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Aortic valve insufficiency; Beta-blocker