The EMPA-AHF trial is a multicentre, randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of early initiation of once-daily oral empagliflozin 10 mg in patients hospitalized for patients with acute heart failure (AHF) who are at a high risk of adverse events.

Inclusion Criteria:

Patients who meet the below inclusion criteria will be randomized within 12 h after presentation to the hospital

1. Age of ≥20*

2. Hospitalized with a diagnosis of acute heart failure, requiring intravenous loop diuretic therapy, and with all of the following characteristics:

   i. Dyspnoea at rest or induced by slight exertion ii. At least two of the following findings: jugular venous distention, pulmonary rales, lower leg edema, and pulmonary congestion on chest X-ray iii. If the patient has a sinus rhythm at the time of admission, BNP ≥350 pg/mL or NT-proBNP ≥1400 pg/mL; if the patient has atrial fibrillation at the time of admission, BNP ≥500 pg/mL or NT-proBNP ≥2000 pg/mL. For patients taking an angiotensin receptor neprilysin inhibitor, only the reference value for NT-proBNP will be applicable.

3. At least one of the following characteristics:

   i. eGFR <60 mL/min/1.73m2, as calculated using the CKD Epidemiology Collaboration for JapaneseModification of Diet in Renal Disease formula ii. Already taking ≥40 mg of oral furosemide during the period before hospitalization. For patients on loop diuretics other than furosemide, the following conversion should be used: oral furosemide 20 mg = oral azosemide 30 mg = oral torasemide 5 mg.

   iii. Urine output of <300 mL during the 2 h following an appropriate dose of intravenous furosemide administered after hospitalization. An appropriate dose of intravenous furosemide is 20 mg for patients who have not been taking furosemide regularly before hospitalization and is the same as, or greater than, the daily oral dose for patients who have been taking furosemide regularly before hospitalization.

4. Provided written consent to participate in the study *If the patient is 90 years of age or older and cognitive decline is considered necessary, Mini-Cog should be used to confirm that its score is not less than 3.

Exclusion Criteria:

1. eGFR <20 mL/min/1.73m2 at the time of admission
2. Already taking an SGLT2i within 3 months prior to hospitalization
3. Type 1 diabetes mellitus
4. Systolic blood pressure <90 mmHg
5. Expected to newly require treatment with thiazide, tolvaptan, or carperitide within 48 hours of study drug administration
6. Main cause of acute heart failure hospitalization is not fluid retention (e.g., persistent ventricular tachycardia, persistent atrial fibrillation/atrial flutter with a ventricular response rate of ≥130 bpm, persistent bradycardia with a ventricular response rate of <45 bpm, an infection, severe anemia, and an acute exacerbation of COPD)
7. Acute coronary syndrome, pulmonary thromboembolism, or a cerebrovascular accident is the main cause of the present hospitalization.
8. At risk of ketoacidosis or hyperosmolar hyperglycaemia
9. On dialysis, including peritoneal dialysis, or the initiation of dialysis during hospitalization is planned
10. Pregnant or lactating women
11. Underwent the following therapeutic interventions within 30 days: cardiovascular surgery (e.g., coronary artery bypass grafting, surgery for valvular heart disease, transcatheter aortic valve implantation, percutaneous coronary intervention, percutaneous edge-to-edge mitral valve repair, and other types of surgery at the investigator's discretion) and implantation of an implantable defibrillator, cardiac resynchronization therapy defibrillator, or implantable ventricular-assist device
12. A diagnosis of acute coronary syndrome, cerebral infarction, or transient ischemic attack made within 90 days
13. Ventricular tachycardia with syncope within 90 days
14. Heart transplant recipient or listed for heart transplantation and expected to undergo transplantation during the present treatment; implanted with an implantable ventricular-assist device or expected to require an implantable ventricular-assist device during the present treatment; or expected to switch to palliative care
15. Intubated at the time of screening or expected to require intubation within within 48 hours of study drug administration
16. Severe valvular heart disease expected to be treated with thoracostomy or catheterization (a reason to exclude secondary mitral or tricuspid regurgitation due to reduced cardiac function does not exist, except for the absence of a plan to perform cardiac surgery or therapeutic catheterization)
17. A diagnosis of secondary cardiomyopathy such as amyloidosis, cardiac sarcoidosis, hemochromatosis, Fabry disease, and muscular dystrophy. Heart failure due to takotsubo cardiomyopathy, obstructive hypertrophic cardiomyopathy, complex congenital heart disease (as determined by the investigator), or pericardial constriction.
18. A diagnosis of peripartum cardiomyopathy made within 6 months
19. Active myocarditis
20. Presence of uncontrolled thyroid disease
21. Acute cardiac structural abnormalities (e.g., acute mitral regurgitation due to ruptured chordae tendineae)
22. Symptomatic bradycardia or complete atrioventricular block, being treated with a temporary pacemaker implantation at the time of admission, or expected to require a temporary pacemaker implantation in the future. Patients who have already been treated with a permanent pacemaker implantation do not meet the exclusion criteria.
23. Serious liver disorder (an increase in AST, ALT, or ALP level ≥3 times the upper limit of normal) or cirrhosis with varices or other findings suggestive of portal hypertension
24. Alcohol use disorder of at least mild severity according to the DSM-V
25. A diagnosis of active malignancy or suspected active malignancy made within 2 years
26. Coexisting diseases other than heart failure with an expected survival prognosis of ≤1 year
27. Participation in a clinical study of another drug 30 days before hospitalization
28. Patients considered to require fasting at screening.
29. Other conditions likely to interfere with the patient's safety or compliance with the protocol
30. Other patients who are considered unsuitable by the principal investigator or other investigators