Interleukin (IL)-1 Blockade in Acute Heart Failure (Anakinra ADHF)

Inclusion Criteria:

All 5 criteria need to be met for enrollment of the patient in the study

1. Primary diagnosis of acute decompensated heart failure within the last 24 hours as
evidenced by both of the following:

1. dyspnea or respiratory distress or tachypnea at rest or with minimal exertion

2. evidence of elevated cardiac filling pressure or pulmonary congestion (at least
one of the conditions must be met);

i. pulmonary congestion/edema at physical exam OR chest x-ray; ii. plasma Brain
Natriuretic Peptide (BNP) levels ≥200 pg/mL; iii.invasive measurement of left
ventricular end-diastolic pressure >18 mmHg or of pulmonary artery occluding pressure
(wedge) >16 mmHg.

2. Left ventricular systolic dysfunction (LVEF<40%) during index hospitalization or
prior 12 months.

3. Age ≥18 years old

4. Willing and able to provide written informed consent.

5. Screening plasma C-reactive protein levels >5 mg/L.

Exclusion Criteria Subjects will not be eligible if they meet any of the following 15
exclusion criteria.

1. The primary diagnosis for admission is NOT decompensated heart failure, including
diagnosis of acute coronary syndromes, hypertensive urgency/emergency, tachy- or
brady-arrhythmias.

2. Concomitant clinically significant comorbidities that would interfere with the
execution or interpretation of the study including but not limited to acute coronary
syndromes, uncontrolled hypertension or orthostatic hypotension, tachy- or
brady-arrhythmias, acute or chronic pulmonary disease or neuromuscular disorders
affecting respiration.

3. Recent (previous 3 months) or planned cardiac resynchronization therapy (CRT),
coronary artery revascularization procedures, or heart valve surgeries.

4. Previous or planned implantation of left ventricular assist devices or
heart-transplant.

5. Chronic use of intravenous inotropes.

6. Recent (<14 days) use of immunosuppressive or anti-inflammatory drugs (not including
Non-Steroidal Anti-Inflammatory Drugs [NSAIDs]).

7. Chronic inflammatory disorder (including but not limited to rheumatoid arthritis,
systemic lupus erythematosus).

8. Active infection (of any type);

9. Chronic/recurrent infectious disease (including Hepatitis B virus [HBV], Hepatitis C
virus [HCV], and HIV/AIDS).

10. Prior (within the past 10 years) or current malignancy.

11. Any comorbidity limiting survival or ability to complete the study.

12. End stage kidney disease requiring renal replacement therapy.

13. Neutropenia (<2,000/mm3) or Thrombocytopenia (<50,000/mm3).

14. Pregnancy.

15. Angina, arrhythmias, or electrocardiograph (ECG) changes that limit maximum exertion
during cardiopulmonary exercise testing obtained during the baseline testing.