Table 1 Inclusion and exclusion criteria of REDHART2 study

Age ≥ 21 years old

LVEF ≤ 40% in the last 12 months with any imaging modality

Primary diagnosis for hospitalization admission is decompensated heart failure with both conditions:

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

2.Evidence of elevated cardiac filling pressure or pulmonary congestion

(one of the following met):

•Pulmonary congestion/edema at physical exam OR chest X-Ray

•Plasma BNP levels ≥ 200 pg/mL OR NTproBNP ≥ 600 pg/mL

•Invasive measurement of LVEDP > 18 mmHg OR PA occluding pressure (wedge) > 16 mmHg

Clinically stable, euvolemic, and meets standard criteria for hospital discharge as documented by all 3 of the conditions listed below:

1.Absence of dyspnea or pulmonary congestion/distress at rest

2.Absence of pitting edema in the lower extremities, or in any other region

3.Stable hemodynamic parameters (blood pressure, heart rate)

Willing and able to comply with the protocol (i.e., self-administration, exercise test, screening CRP)

CRP > 0.3 mg/dL or hsCRP > 2 mg/L

Exclusion criteria

The primary diagnosis for admission is NOT decompensated heart failure (i.e., acute coronary syndromes, hypertensive urgency/emergency, tachy- or brady-arrhythmias)

Concomitant comorbidities that would interfere with the execution or interpretation of the study (i.e., uncontrolled hypertension, orthostatic hypotension, tachy- or brady-arrhythmias, acute or chronic pulmonary disease, or neuromuscular disorders affecting respiration, peak respiratory exchange ratio (VCO₂/VO₂) < 1.0, or with angina, abnormal blood pressure or heart rate response, or ECG changes suggestive of coronary ischemia that limit maximum exertion during CPX obtained during the baseline testing

Cardiac resynchronization therapy (CRT) during index hospitalization, or planned CRT or valvular heart surgery within the following 6 months

Previous or planned implantation of left ventricular assist devices or heart transplant

Chronic use of intravenous inotropes

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 oral NSAIDs)

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

Current malignancy (excluding carcinoma in situ [any location] or localized non-melanoma skin cancer) receiving targeted therapy

Any comorbidity limiting survival or ability to complete the study

Evidence of COVID-19 within the last 60 days or recent (21 days) exposure to close personal contact

Stage V kidney disease (eGFR < 15 mL/min/1.73m²) or on renal-replacement therapy

Neutropenia (< 1500/mm³ or < 1000/mm³ in African American patients)

Pregnancy

Hypersensitivity to Kineret (anakinra) or to E. coli-derived products