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

Aortic Valve Insufficiency Clinical Trial

— BAR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01157572
• Other study ID #: EUDRACTNR: 2007-000518-34
• Status: Completed
• Phase: Phase 4
• First received: July 5, 2010
• Last updated: September 24, 2014
• Start date: August 2010
• Est. completion date: September 2014

Study information

• Verified date: September 2014
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Norway: Norwegian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: September 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Moderate to severe aortic valve insufficiency

• Asymptomatic

Exclusion Criteria:

• Arrhythmia

• Other severe valve disease

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Aortic Valve Insufficiency
• Ventricular Remodeling

Intervention

Drug:
• Metoprolol
Patients with moderate to severe aortic valve insufficiency will be randomized to Metoprolol
• Placebo
Patients with moderate to severe aortic valve insufficiency will be randomized to Placebo

Locations

Country	Name	City	State
n/a

Sponsors (5)

Lead Sponsor	Collaborator
Oslo University Hospital	Haukeland University Hospital, University Ghent, University Hospital, Akershus, University Hospital, Gentofte, Copenhagen

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Left ventricular end-diastolic volume		6 months	Yes
Secondary	Left ventricular end-systolic volume		6 months	Yes