CR Aim #2 - AT1 Receptor Blockade & ACE Inhibition Effect on Humoral Function

Inclusion Criteria

• Left ventricular ejection fraction of equal or less than 40% assessed by echocardiography, nuclear scan, MRI or left ventriculogram within the past 48 months.
• Stable New York Heart Association (NYHA) class II and III symptoms as defined by: no change in NYHA symptoms over the past 3 months, on stable doses of ACE inhibitor, beta blocker, digoxin and furosemide over the last 4 weeks and no episode of decompensated CHF over the past 6 months.
• Calculated creatinine clearance of equal or less than 80 ml/min and greater than 20 ml/min, using the MDRD formula assessed within the past 48 months and a confirmatory calculated creatinine clearance equal or less than 80 ml/min and greater than 20 ml/min at the time of enrollment.

Subjects who are already taking AT1 receptor blocker will be excluded. Aldosterone antagonist, antiarrhythmic medications and other vasodilators will be allowed; however, all medications must be at stable doses 4 weeks prior to enrollment. Subjects taking nonsteroidal anti-inflammatory drugs (NSAIDs) except aspirin will not be able to increase their medication dose for the duration of the study. Subjects will be excluded if they have had a prior diagnosis of intrinsic renal disease, including renal artery stenosis of > 50%, or if they meet any one of the exclusion criteria listed below.

Exclusion Criteria

• Prior diagnosis of intrinsic renal diseases including renal artery stenosis of > 50%
• Peritoneal or hemodialysis within 90 days or anticipation that dialysis or ultrafiltration of any form will be required during the study period
• Hospitalization for decompensated CHF during the past 6 months
• Subjects that are taking AT1 receptor blockers
• Myocardial infarction within 6 months of screening
• Unstable angina within 6 months of screening, or any evidence of myocardial ischemia
• Significant valvular stenosis, hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or biopsy proven active myocarditis
• Severe congenital heart diseases
• Sustained ventricular tachycardia or ventricular fibrillation within 14 days of screening
• Second or third degree heart block without a permanent cardiac pacemaker
• Stroke within 3 months of screening, or other evidence of significantly compromised CNS perfusion
• ALT >1.5 times the upper limit of normal
• Serum sodium of 160 mEq/dL
• Serum potassium of 5.7 mEq/dL
• Serum digoxin level of > 2.0 ng/ml
• Hemoglobin < 9 gm/dl
• Other acute or chronic medical conditions or laboratory abnormality which may increase the risks associated with study participation or may interfere with interpretation of the data
• Received an investigational drug within 1 month prior to dosing
• Patients with an allergy to iodine.
• Female subject who is pregnant or breastfeeding
• In the opinion of the investigator, is unlikely to comply with the study protocol or is unsuitable for any reasons