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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01157572
Recruitment Status : Completed
First Posted : July 7, 2010
Last Update Posted : September 25, 2014
University Ghent
University Hospital, Gentofte, Copenhagen
University Hospital, Akershus
Haukeland University Hospital
Information provided by (Responsible Party):
Stig Urheim, Oslo University Hospital

Brief 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.

Condition or disease Intervention/treatment Phase
Aortic Valve Insufficiency Drug: Metoprolol Drug: Placebo Phase 4

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Beta Blockade on Left Ventricular Remodeling and Function in Moderate to Severe Asymptomatic Aortic Regurgitation
Study Start Date : August 2010
Actual Primary Completion Date : August 2014
Actual Study Completion Date : September 2014

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Metoprolol Drug: Metoprolol
Patients with moderate to severe aortic valve insufficiency will be randomized to Metoprolol
Placebo Comparator: Placebo Drug: Placebo
Patients with moderate to severe aortic valve insufficiency will be randomized to Placebo

Primary Outcome Measures :
  1. Left ventricular end-diastolic volume [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Left ventricular end-systolic volume [ Time Frame: 6 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Moderate to severe aortic valve insufficiency
  • Asymptomatic

Exclusion Criteria:

  • Arrhythmia
  • Other severe valve disease

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Stig Urheim, MD, PhD, Oslo University Hospital Identifier: NCT01157572     History of Changes
Other Study ID Numbers: EUDRACTNR: 2007-000518-34
First Posted: July 7, 2010    Key Record Dates
Last Update Posted: September 25, 2014
Last Verified: September 2014

Keywords provided by Stig Urheim, Oslo University Hospital:
Aortic valve insufficiency

Additional relevant MeSH terms:
Ventricular Remodeling
Aortic Valve Insufficiency
Pathological Conditions, Anatomical
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Anti-Arrhythmia Agents
Antihypertensive Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action