Molecular Mechanisms of Volume Overload-Aim 1(SCCOR in Cardiac Dysfunction and Disease)

• Status: Completed
• Trial end date: 2010-07-01
• Target enrollment: 0
• Participant gender: All

Summary

The investigators hypothesize that beta-1 receptor blockade (ß1-RB) attenuates extracellular matrix (ECM) degradation and progressive adverse Left Ventricular (LV) remodeling and failure in the volume overload of mitral regurgitation (MR). Patients without coronary artery disease and moderate MR, as assessed by color/flow Doppler echocardiography, will be randomized to ß1-RB vs. placebo to address the following aims:

*Aim 1: Establish whether ß1-RB attenuates adverse LV remodeling compared to placebo in patients with non-surgical, chronic MR. Using 3-dimensional magnetic resonance imaging (MRI) and tissue tagging, LV function and geometry will be assessed at baseline and every 6 months for up to 2 years.

Aim 2: Determine whether indices of inflammation correlate with degree of LV remodeling and whether ß1-RB decrease indices of inflammation and collagen turnover. At the time of MRI, blood samples for collagen breakdown products, matrix metalloproteinase (MMP) activity, and markers of excess production of reactive inflammatory species (RIS) will be obtained and related to changes in LV remodeling defined by serial 3-dimensional MRI and tissue tagging.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Alabama at Birmingham
• Collaborators: AstraZeneca; National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Metoprolol

Criteria

Inclusion Criteria:Patients who have Moderate MR documented by color flow doppler:

1. LV ejection fraction > 55%; LV end-systolic dimension < 4.0 cm.

2. Quantifiable by Doppler-Echo equal or more than moderate in severity.

3. Organic disease of the mitral valve demonstrated by echocardiography (not normal valve as in functional or ischemic MR).

4. Isolated MR (no valve disease other than mild tricuspid or pulmonic regurgitation by Doppler-Echocardiography that is often associated with mitral valve prolapse).

5. Asymptomatic (or mildly symptomatic but not considered as candidates for immediate surgery by their attending physician).

Exclusion Criteria:

1. Significant obstructive coronary artery disease and/or myocardial ischemia on graded exercise test with myocardial perfusion.

2. Previous myocardial infarction or percutaneous coronary intervention.

3. Hypertrophic cardiomyopathy, congenital or pericardial disease.

4. Aortic valve disease (> trace aortic regurgitation or mean gradient > 10 mmHg).

5. Mitral stenosis (mean gradient >5 mmHg, valve area < 1.5 cm2).

6. Intolerance or contraindication to Beta1-AR blockade.

7. Renal failure with creatinine > 2.5 mg/dl.

8. Hypertension requiring medical treatment or renal artery stenosis.

9. Severe comorbidity: liver disease, malignancy, collagen vascular, steroid requirement.

10. Pregnancy (negative pregnancy test and effective contraceptive methods are required prior to enrollment of females of childbearing potential).

11. Uncontrolled (rate > 120/min) or recent (<4 weeks) atrial fibrillation.

12. Routine, regular use of anti-inflammatory medications.

Exclusion Criteria Related to MRI

1. Severe claustrophobia.

2. Presence of a pacemaker or non-removable hearing aid.

3. Presence of metal clips in the body.