Reversing Endothelial and Diastolic Dysfunction and Improving Collagen Turnover in Diastolic Heart Failure
Reversing Endothelial and Diastolic Dysfunction and Improving Collagen Turnover in Diastolic Heart Failure
The principle aim is to determine the efficacy of eplerenone in patients with diastolic heart
 failure to reverse cardiac remodeling and to improve diastolic function.
The study will be a single center, double-blind, randomized, parallel group trial enrolling a
 minimum of 80 patients designed to determine the efficacy of eplerenone in subjects with
 diastolic heart failure. Prior to administration of study medication, a medical history,
 physical exam, blood draw, electrocardiogram, 2D echocardiogram, and cardiomyopathy
 questionnaire will be performed. Subjects will then be randomized to receive either
 eplerenone 25 mg once daily or placebo for 2 weeks. At the Week 2 visit all patients will be
 titrated up to the next dose (50 mg eplerenone once daily or placebo). Each study arm will
 have 40 subjects who will participate for 9 months. Follow-up assessments will be completed
 at 1 week, 2 weeks, 1 month, 3 months, 6 months, and 9 months.

 Starting at the Month 1 visit, any subjects with uncontrolled blood pressure will be
 administered add-on therapy of HCTZ (starting dose of 12.5 mg daily, that may titrate up to
 25 mg daily) and/or amlodipine (starting dose at 5 mg daily, that may titrate up to 10 mg
 daily). Any subject who receives add-on therapy must have their blood pressure checked within
 2 weeks. Uncontrolled blood pressure may be treated by either increasing the add-on therapy
 dose or increasing the add-on therapy regimen to include both add-on drugs. Changes in add-on
 therapy require blood pressure checks within 2 weeks.
Inclusion Criteria:

 Patients must meet all of the following inclusion criteria to be eligible for enrollment
 into the study:

 1. Male or non-pregnant female (if female, either post-menopausal, or if of child-bearing
 potential, using adequate contraception e.g. hormonal or barrier methods, or
 surgically sterile, and not lactating)

 2. Age >/= 18 years of age

 3. Present or prior history of symptoms of heart failure (dyspnea, fatigue) consistent
 with diagnosis of diastolic heart failure, following optimized medical therapy
 including blood pressure control with ACE inhibitors and/or beta-blockers for 2 weeks
 or over.

 4. Echocardiographic evidence of preserved left ventricular systolic function (LVEF >/=
 45%) and evidence of diastolic dysfunction (by transmitral inflow, pulmonary venous
 flow, color M-mode and/or tissue Doppler).

 5. Signed informed consent

 Exclusion Criteria:

 The presence of any of the following will exclude a patient from study enrollment:

 1. Unwilling to participate for the 9-month duration of the study

 2. Significant primary valvular, pulmonary or congenital cardiac disease believed to be
 the cause of dyspnea

 3. Life expectancy or planned cardiac transplantation <9 months

 4. History of hypertrophic obstructive cardiomyopathy

 5. Unstable angina or ischemia requiring revascularization

 6. Renal insufficiency (Cr >2.0 mg/dL in males and >1.8 mg/dl in females, or modified
 Cockcroft-Gault estimate of creatinine clearance <30 mL/min) at enrollment

 7. Known hypersensitivity to spironolactone or eplerenone

 8. Decompensated heart failure or clinical evidence of instability at the time of
 enrollment 9 History of hyperkalemia (>6.0 mg/dL) with spironolactone

 10. Use of spironolactone or amiloride within 30 days 11. Poorly controlled seating blood
 pressure at the time of drug initiation:

 -  Systolic blood pressure >160 mmHg; and/or

 -  Diastolic blood pressure >100 mmHg