Effect of Beta Blockade on Left Ventricular Remodeling and Function in Moderate to Severe Asymptomatic Aortic Regurgitation

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effect of Beta Blockade on Left Ventricular Remodeling and Function in Moderate to Severe Asymptomatic Aortic Regurgitation

Conditions
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Aortic Valve Insufficiency

Intervention / Treatment
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* Drug: Metoprolol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Moderate to severe aortic valve insufficiency Asymptomatic Exclusion Criteria: Arrhythmia Other severe valve disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metoprolol<br> | Drug: Metoprolol<br>* Patients with moderate to severe aortic valve insufficiency will be randomized to Metoprolol<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Patients with moderate to severe aortic valve insufficiency will be randomized to Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular end-diastolic volume |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular end-systolic volume |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aortic valve insufficiency, Beta-blocker