Circulating NEP and NEP Inhibition Study in Heart Failure With Preserved Ejection Fraction

Inclusion Criteria 1. Age ≥ 50 years 2. LVEF ≥ 45% assessed by echocardiography, nuclear scan, MRI or left ventriculogram within the past 24 months 3. Current New York Heart Association (NYHA) class 2-4 symptoms of heart failure (HF) 4. Stable medical therapy for 30 days as defined by: 1. No addition or removal of ACE, ARB, beta-blockers, calcium channel blockers (CCBs) or aldosterone antagonists 2. No change in dosage of ACE, ARBs, beta-blockers, CCBs or aldosterone antagonists of more than 100% 5. One of the following within the last 24 months 1. Previous hospitalization for HF with radiographic evidence of pulmonary congestion (pulmonary venous hypertension, vascular congestion, interstitial edema, pleural effusion) or 2. Catheterization documented elevated filling pressures at rest (LVEDP≥15 or PCWP≥20) or with exercise (PCWP≥25) or 3. Elevated NT-proBNP (\> 400 pg/ml) or BNP (\> 200 pg/ml) or 4. Echo evidence of diastolic dysfunction / elevated filling pressures (at least two) i. E/A \> 1.5 + decrease in E/A of \> 0.5 with valsalva ii. Deceleration time ≤ 140 ms iii. Pulmonary vein velocity in systole \< diastole (PVs\<PVd) (sinus rhythm) iv. E/e'≥15 v. Left atrial enlargement (≥ moderate) vi. Pulmonary artery systolic pressure \> 40 mmHg vii. Evidence of left ventricular hypertrophy 1. LV mass/BSA ≥ 96 (♀) or ≥ 116 (♂) g/m2 2. Relative wall thickness ≥ 0.43 (♂ or ♀) \[(IVS+PW)/LVEDD\] 3. Posterior wall thickness ≥ 0.9 (♀) or 1.0 (♂) cm Exclusion Criteria 1. History of hypersensitivity or allergy to ACE inhibitors (ACEIs), ARBs, or NEP inhibitors 2. Known history of angioedema 3. Previous LVEF \< 40% at any time 4. Systolic blood pressure \< 100 mmHg or \> 180 mmHg 5. Current acute decompensated HF (exacerbation of chronic HF manifested by signs and symptoms that may require intravenous therapy) 6. Unstable angina, myocardial infarction, stroke, transient ischemic attack, or cardiovascular surgery or urgent percutaneous coronary intervention (PCI) within 3 months of screening or elective PCI within 30 days of entry 7. Significant valvular stenosis or regurgitation (greater than moderate in severity), hypertrophic, restrictive or obstructive cardiomyopathy including amyloidosis, constrictive pericarditis, primary pulmonary hypertension, or biopsy proven active myocarditis 8. Severe congenital heart disease 9. History of heart transplant or with LV assist device 10. Evidence of severe hepatic disease as determined by any one of the following: history of hepatic encephalopathy, history of esophageal varices, or history of porto-caval shunt. 11. Glomerular filtration rate \< 20 ml/min/1.73 m2 on most recent clinical laboratories\* 12. Serum potassium of \> 5.5 mEq/dL on most recent clinical laboratories\* 13. Concomitant use of aliskiren in patients with diabetes 14. Currently receiving an investigational drug 15. Inability to comply with planned study procedures 16. Female subject who is pregnant or breastfeeding * Performed within 90 days of enrollment