This will be a randomized, double-blind, crossover pilot study to measure the safety and feasibility of Interleukin-1 (IL-1) blockade with Anakinra in patients with stable heart failure with preserved ejection fraction.

Inclusion Criteria:

• Symptoms and signs of congestive heart failure

• Recent Imaging Study (<12 months) showing Left Ventricular Ejection Fraction (LVEF) >50% and Left Ventricular End Diastolic Volume Index (LVEDVI) <97ml/m2

• Evidence of abnormal Left Ventricular (LV) relaxation, filling, diastolic distensibility, and diastolic stiffness as shown by one of the following:

  1. Invasive Hemodynamic measurements

     • mean Pulmonary Capillary Wedge pressure (mPCW) >12
     • Left Ventricular End Diastolic Pressure (LVEDP) >16 mmHg

  2. Tissue Doppler Echocardiogram

     • E/E' >15

     • E/E' 8-15 and one of the following

       • Left Ventricular Hypertrophy (LVH)
       • Atrial Fibrillation
       • Left Atrial Enlargement
       • E/A <0.5 + Deceleration Time (DT) >280 (if >50yrs of age)

  3. Biomarkers

• Brain Natriuretic Peptide (BNP) >200pg/mL

Exclusion Criteria:

• Age <18
• Recent changes (previous 3 months) in HF maintenance medications (beta-blockers, angiotensin converting enzyme [ACE] inhibitors, aldosterone antagonists, vasodilators, cardiac glycosides, diuretics)
• Hospitalization for worsening Heart Failure (HF) or acute decompensated HF within the previous 12months
• Anticipated need for cardiac resynchronization therapy (CRT) or automated-implantable cardioverter defibrillator (AICD)
• Angina or electrocardiograph (ECG) changes that limit maximum exertion during cardiopulmonary exercise testing
• Active infection including chronic infection
• Active cancer
• Recent (<14 days) use of anti-inflammatory drugs (not including Non-Steroidal Anti-Inflammatory Drugs [NSAIDs]), Chronic inflammatory disorder (including but not limited to rheumatoid arthritis, systemic lupus erythematosus), malignancy, or any comorbidity limiting survival or ability to complete the study
• Pregnancy (determined by urine pregnancy test in women of childbearing potential)
• Inability to give informed consent
• Other conditions limiting completion of cardiopulmonary exercise test or completion of the study

This is a cross-over trial, so all patients have been treated with anakinra and with placebo at different times.

28 days

This is a pilot study to estimate the effects of targeted anti-inflammatory treatment on aerobic exercise capacity in patients with Heart Failure and Preserved Ejection Fraction. All findings should therefore be considered hypothesis generating.