Aldosterone Antagonism in Diastolic Heart Failure

Inclusion Criteria: All patients must have DHF as defined by all 3 of the following criteria: i)Presence of clinical heart failure for greater than or equal to 2 months before the screening visit. At the time of enrollment they should have NYHA functional class II or III heart failure symptoms such as dyspnea, fatigue on exertion, paroxysmal nocturnal dyspnea, and orthopnea. ii)Left ventricular ejection fraction greater than or equal to 50% (by echo, radionuclide angiography or contrast angiography) within 2 months of screening iii) BNP (brain natriuretic peptide) greater than or equal to 62 pg/ml within 2 months of screening Patients euvolemic on clinical examination. If patients are not euvolemic, all attempts will be made to achieve a euvolemic state with change in diuretic doses prior to enrollment into the study Systolic blood pressure less than or equal to 150 mmHg and diastolic blood pressure less than or equal to 95 mmHg for 4 weeks prior to and at the time of enrollment Able to walk at least 50 m at the time of enrollment All patients will be required to be on ACE inhibitors or angiotensin receptor blockers for at least 4 weeks prior to enrollment Exclusion Criteria: Patients requiring eplerenone or spironolactone for treatment of other comorbid illnesses, e.g. ascites due to cirrhosis. Also, patients with severe hepatic impairment will not be included. Contraindication to eplerenone therapy with creatinine > 2.5 mg/dl or serum potassium > 5.0 mEq/L or creatinine clearance < 30 ml/min/1.73 m2 or intolerance to eplerenone or spironolactone in the past Significant valvular heart disease, pericardial disease or severe chronic lung disease with cor pulmonale, as the cause of symptoms and signs of CHF Patients with technically inadequate echocardiographic windows or patients with severe mitral annular calcification Unstable angina or MI within 4 weeks prior to enrollment Patient with severe peripheral vascular disease and claudication or other physical conditions that will limit the distance walked by them Pregnant or lactating females History of alcohol or substance abuse or history of repeated non-compliance with medications History of cancer within 3 years (other than resected cutaneous basal or squamous cell carcinoma) Participation in any other drug trial within 30 days prior to enrollment Inability to provide informed consent On drugs that are strong inhibitors of CYP3A4 such as ketoconazole, itraconazole, nefazodone, trolandeomycin, clarithromycin, ritonavir, nelfinavir etc.