Angiotensin-II Blockade in Mitral Regurgitation

Patients with MR organic (intrinsic valve disease), isolated (no other valve disease), moderate or more severe (regurgitant volume *30 mL/beat). A Clinical trial, randomized, placebo controlled, double-blind, without cross-over, of 1 year oral treatment with potent angiotensin-II receptor blockade using 32 mg Candesartan daily. The trial is preceded in all patients by an acute open-label study to determine tolerance and immediate response. The methods used to measure the end-points will be: a) Doppler-Echocardiography for quantitation of the degree of MR (measurement of regurgitant volume) using a combination of three simultaneous methods (quantitative Doppler, quantitative two-dimensional echocardiography, proximal flow convergence) and b) of left ventricular remodeling (end-diastolic volume index measured by echocardiography and by electron beam computed tomography). This single center study seeks to enroll a total of 90 patients. The analysis will be based on intention to treat and compare the regurgitant volume and left ventricular end-diastolic volume index measured after one year of treatment with the active drug or placebo. The results of the trial should provide strong evidence regarding medical treatment of patients with organic MR.

Inclusion criteria

Patients:

• 18 years old or older, with
• Mitral regurgitation on the basis of Color flow imaging
• Due to organic disease of the mitral valve on the basis of two-dimensional echocardiography
• Isolated (no valve disease other than functional tricuspid regurgitation on the basis of Doppler-Echocardiography)
• Pure (no mitral stenosis by Doppler echocardiography)
• Quantifiable by Doppler-Echocardiographic methods
• Of more than mild degree, defined as regurgitant volume * 30 mL/beat
• Occurring on native valves
• With Two-dimensional echocardiographic imaging allowing assessment of LV remodeling, and
• Asymptomatic (or mildly symptomatic but not considered as candidates for immediate surgery by their attending physician).

Exclusion criteria

• Associated aortic valve disease (more than trace aortic regurgitation by color flow imaging or mean gradient *25 mmHg)
• Associated mitral stenosis (mean gradient* 5 mmHg, valve area < 1.5 cm2)
• Associated congenital or pericardial diseases on the basis of Doppler echocardiography
• Intolerance to either AII blockers or Angiotensin converting enzyme inhibitors
• Intolerance to iodine contrast material
• Intolerance to intravenous echographic contrast agents
• Renal failure with creatinine * 2 mg/dl
• Blood pressure below 100 mmHg
• Known renal artery stenosis
• Ongoing therapy with hydralazine, calcium-entry blocking drugs or angiotensin converting enzyme inhibitors
• Known severe comorbidity such as liver disease, malignancy
• Pregnancy (A negative pregnancy test and effective contraceptive methods are required prior to enrollment of females of childbearing potential (not post-menopausal or surgically sterilized)), and
• Patients considered as requiring mitral valve surgery by their attending physician or with previous valve repair or replacement.