This study will explore the potential benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors in preventing cardiac ischemia and cardiopulmonary edema in patients with acute decompensated heart failure during weaning from ventilators.

Patients with acute decompensated HF will be open-label randomly assigned to be treated with or without SGLT2 inhibitors (either empagliflozin 10 mg once daily or dapagliflozin 10 mg once daily) 3 days before ventilator weaning in a ratio of 2:1. If the patients are allocated to SGLT2i treatment group, they will be further randomized equally to either empagliflozin- or dapagliflozin-treated group. A series of examination will be performed to detect weaning-induced cardiac ischemia and weaning-induced cardiopulmonary edema, including electrocardiography, chest X-ray, echocardiography, and biomarkers.

Echocardiography Transthoracic echocardiography (TTE) will be performed by a trained operator at several time points: (1) before SBT and SGLT2i initiation; (2) during SBT trial just after initiating SGLT2 inhibitor; (3) during SBT trial 3 days after initiation of SGLT2 inhibitor; (4) within 24 hrs after extubation; (5) 7-10 days after extubation; (6) 90±7 days after extubation.

Biomarkers NT-proBNP, plasma protein, high-sensitive cardiac troponin T, and hemoglobin level will be checked at several time points: (1) before spontaneous breathing trial (SBT), (2) during SBT trial (at least 10 mins after the initiation of SBT) just after initiating SGLT2 inhibitor; (3) during SBT (at least 10 mins after the initiation of SBT) trial 3 days after SGLT2 inhibitor; (4) within 24 hrs after extubation; (5) 7~10 days after extubation; (5) 90±7 days after extubation. We will also check arterial blood gas analyses at the end of SBT trial just after initiating SGLT2 inhibitor and 3 days after SGLT2 inhibitor.

Inclusion Criteria:

1. Patients aged ≥20 years

2. Currently hospitalized for the primary diagnosis of acute HF (de novo or decompensated chronic HF) in HFrEF patients (LVEF≤40%)

3. Meet the stabilization criteria:

   A. Systolic BP ≥100mm Hg and no symptoms of hypotension in the preceding 6 hours B. No increase in i.v. diuretic dose for 6 hours prior to randomization C. No i.v. vasodilators including nitrates within the last 6 hours prior to randomization D. No i.v. inotropic drugs for 24 hours prior to randomization

4. Elevated N-terminal proB-type natriuretic peptide (NT-proBNP) or BNP:

   A. Without atrial fibrillation (AF): NT-proBNP ≥1600 pg/mL or BNP ≥400 pg/mL B. With AF: NT-proBNP ≥2400 pg/mL or BNP ≥600 pg/mL

5. Patients were intubated for at least 24 hour with ventilator settings allowing to initiate the weaning process [SpO2 > 90% or PaO2/FiO2 ≥ 150 mmHg with a fraction of inspired oxygen (FiO2) ≤ 40% and a positive end-expiratory pressure (PEEP) ≤ 8 cmH2O].

Exclusion Criteria:

1. Decision to withdraw life support
2. Cardiogenic shock
3. Hospitalization for HF (HHF) triggered by acute myocardial infarction (AMI) or pulmonary embolism
4. Planned or previous (within 30 days) cardiovascular revascularization or major cardiac surgery/intervention/device implantation
5. Prior acute coronary syndrome, AMI, stroke or transient ischemic accident within 90 days
6. Estimated glomerular filtration rate (eGFR) of less than 30 ml per minute per 1.73 m2 of body-surface area
7. Type 1 diabetes mellitus
8. Poorly controlled type 2 diabetes mellitus (a glycated hemoglobin level above 10.5%)
9. Uncontrolled urinary tract infection