Early Treatment With a Sodium-glucose Co-transporter 2 Inhibitor in High-risk Patients With Acute Heart Failure

Inclusion Criteria:

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

1. Age of ≥20 and <90 years

2. Hospitalized with a diagnosis of acute heart failure, requiring intravenous loopdiuretic therapy, and with all of the following characteristics: i. Dyspnoea at rest or induced by slight exertion ii. At least two of the followingfindings: jugular venous distention, pulmonary rales, lower leg edema, and pulmonarycongestion on chest X-ray iii. If the patient has a sinus rhythm at the time ofadmission, BNP ≥350 pg/mL or NT-proBNP ≥1400 pg/mL; if the patient has atrialfibrillation at the time of admission, BNP ≥500 pg/mL or NT-proBNP ≥2000 pg/mL. Forpatients taking an angiotensin receptor neprilysin inhibitor, only the referencevalue 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 Collaborationfor JapaneseModification of Diet in Renal Disease formula ii. Already taking ≥40 mgof oral furosemide during the period before hospitalization. For patients on loopdiuretics other than furosemide, the following conversion should be used: oralfurosemide 20 mg = oral azosemide 30 mg = oral torasemide 5 mg. iii. Urine output of <300 mL during the 2 h following an appropriate dose ofintravenous furosemide administered after hospitalization. An appropriate dose ofintravenous furosemide is 20 mg for patients who have not been taking furosemideregularly before hospitalization and is the same as, or greater than, the daily oraldose for patients who have been taking furosemide regularly before hospitalization.

4. Provided written consent to participate in the study

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 flutterwith a ventricular response rate of ≥130 bpm, persistent bradycardia with aventricular response rate of <45 bpm, an infection, severe anemia, and an acuteexacerbation of COPD)

7. Acute coronary syndrome, pulmonary thromboembolism, or a cerebrovascular accident isthe 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 duringhospitalization is planned

10. Pregnant or lactating women

11. Underwent the following therapeutic interventions within 30 days: cardiovascularsurgery (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 theinvestigator's discretion) and implantation of an implantable defibrillator, cardiacresynchronization therapy defibrillator, or implantable ventricular-assist device

12. A diagnosis of acute coronary syndrome, cerebral infarction, or transient ischemicattack made within 90 days

13. Ventricular tachycardia with syncope within 90 days

14. Heart transplant recipient or listed for heart transplantation and expected toundergo transplantation during the present treatment; implanted with an implantableventricular-assist device or expected to require an implantable ventricular-assistdevice 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 orcatheterization (a reason to exclude secondary mitral or tricuspid regurgitation dueto reduced cardiac function does not exist, except for the absence of a plan toperform 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 totakotsubo cardiomyopathy, obstructive hypertrophic cardiomyopathy, complexcongenital heart disease (as determined by the investigator), or pericardialconstriction.

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 toruptured chordae tendineae)

22. Symptomatic bradycardia or complete atrioventricular block, being treated with atemporary pacemaker implantation at the time of admission, or expected to require atemporary pacemaker implantation in the future. Patients who have already beentreated 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 upperlimit of normal) or cirrhosis with varices or other findings suggestive of portalhypertension

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 withthe protocol

30. Other patients who are considered unsuitable by the principal investigator or otherinvestigators