Interleukin-1 Blockade In Recently Decompensated Heart Failure - 2

Prior treatment

• 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.
• Recent (previous 3 months) or planned resynchronization therapy (CRT), or valve surgeries.
• Previous or planned implantation of left ventricular assist devices or heart transplant.
• Recent (\<14 days) use of immunosuppressive or anti-inflammatory drugs (including oral corticosteroids at a dose of prednisone equivalent of 0.5 mg/kg/day but not including inhaled or low dose oral corticosteroids or non-steroidal anti-inflammatory drugs).

Other illness

• The primary diagnosis for admission is NOT decompensated heart failure, including diagnosis of acute coronary syndromes, hypertensive urgency/emergency, tachy- or brady-arrhythmias.
• Chronic inflammatory disorder (including but not limited to rheumatoid arthritis, systemic lupus erythematosus).
• Active infection (of any type), including chronic/recurrent infectious disease (i.e. HBV, HCV, and HIV/AIDS) - but excluding HCV+ with undetectable plasma RNA.
• Active malignancy - excluding carcinoma in situ \[any location\] or localized non-melanoma skin cancer.
• Stage V kidney disease or on renal-replacement therapy.
• Angina, hypertension, arrhythmias, electrocardiograph (ECG) changes, or other non-cardiac limitations (i.e., peak respiratory exchange ratio VCO2/VO2 \[RER\]\<1.0, reflecting sub-maximal test) that limit maximum exertion during CPX obtained during the baseline testing.
• Hypersensitivity to Kineret or to E. coli derived products. 16) Evidence of COVID19 within the last 60 days or recent (21 days) exposure to close personal contact.

Other

• Subjects will not be eligible if they meet any of the following 15 exclusion criteria.
• Chronic use of intravenous inotropes.
• Any comorbidity limiting survival or ability to complete the study.
• Neutropenia (\<1,500/mm3 or \<1,000/mm3 in African-American patients).
• Pregnancy.

• All 6 criteria need to be met for enrollment of the patient in the study
• Primary diagnosis for hospitalization is decompensated heart failure established as the finding at admission of both conditions listed below:
  • dyspnea or respiratory distress or tachypnea at rest or with minimal exertion;
  • evidence of elevated cardiac filling pressure or pulmonary congestion (at least one of the conditions must be met):
  • pulmonary congestion/edema at physical exam OR chest XRay;
  • plasma BNP levels ≥200 pg/mL;
  • invasive measurement of left ventricular end-diastolic pressure \>18 mmHg or of pulmonary artery occluding pressure (wedge) \>16 mmHg.
• The patient has a prior documentation of impaired left ventricular systolic function (ejection fraction ≤40%) at most recent assessment by any imaging modality (within 12 months).
• The patient is now clinically stable, euvolemic, and meets standard criteria for hospital discharge as documented by all the 3 conditions listed below:
  • absence of dyspnea or pulmonary congestion/distress at rest;
  • absence of pitting edema in the lower extremities, or in any other region;
  • stable hemodynamic parameters (blood pressure, heart rate).
• The patient is of age ≥21 years old, and is willing and able to provide written informed consent.
• The patient is willing and able to comply with the protocol (i.e., self-administration, or exercise test).
• The patient has screening high sensitivity plasma C-reactive protein levels (hsCRP) \>2 mg/L.