Clinical Trials

Inclusion Criteria:

• Age ≥ 50 years.
• LVEF ≥ 45% assessed by echocardiography, nuclear scan, MRI or left ventriculogram within the past 24 months.
• Current New York Heart Association (NYHA) class 2-4 symptoms of heart failure (HF).
• Stable medical therapy for 30 days as defined by:
  • No addition or removal of ACE, ARB, beta-blockers, calcium channel blockers  (CCBs) or aldosterone antagonists;
  • No change in dosage of ACE, ARBs, beta-blockers, CCBs or aldosterone antagonists of more than 100%.
• Elevated NT-proBNP (>300 pg/ml) or BNP (>200 pg/ml).
• One of the following within the last 12 months:
  • Previous hospitalization for HF with radiographic evidence of pulmonary congestion (pulmonary venous hypertension, vascular congestion, interstitial edema, pleural effusion); or
  • Catheterization documented elevated filling pressures at rest (LVEDP≥15 or PCWP≥20) or with exercise (PCWP≥25); or
  • Echo evidence of diastolic dysfunction / elevated filling pressures (at least two):
    • E/A > 1.5+ decrease in E/A of > 0.5 with valsalva;
    • Deceleration time ≤ 140 ms;
    • Pulmonary vein velocity in systole < diastole (PVs
    • E/e ≥15;
    • Left atrial enlargement (≥ moderate);
    • Pulmonary artery systolic pressure > 40 mmHg;
    • Evidence of left ventricular hypertrophy:
      • LV mass/BSA ≥ 96 (♀) or ≥ 116 (♂) g/m2;
      • Relative wall thickness ≥ 0.43 (♂ or ♀) [(IVS+PW)/LVEDD];
      • Posterior wall thickness ≥ 0.9 (♀) or 1.0 (♂) cm.

Exclusion Criteria:

• History of hypersensitivity or allergy to ACE inhibitors (ACEIs), ARBs, or NEP inhibitors.
• Known history of angioedema to ACE inhibitors (ACEIs) or ARBs.
• Previous LVEF < 40% at any time.
• Systolic blood pressure < 100 mmHg or > 180 mmHg.
• Current acute decompensated HF (exacerbation of chronic HF manifested by signs and symptoms that may require intravenous therapy).
• 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.
• 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.
• Severe congenital heart disease.
• History of heart transplant or with LV assist device.
• 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.
• Glomerular filtration rate < 20 ml/min/1.73 m2 on most recent clinical laboratories.*
• Serum potassium of > 5.5 mEq/dL on most recent clinical laboratories.*
• Concomitant use of aliskiren in patients with diabetes.
• Currently receiving an investigational drug.
• Inability to comply with planned study procedures.
• Female subject who is pregnant or breastfeeding.
• * Performed within 90 days of enrollment