Heart failure (HF) is one of the most important reasons for hospital admission and is associated with high mortality and morbidity. After discharge, up to 40% of patients are readmitted within 6 months and 1-year post-discharge mortality is high. The cost burden of treating patients with HF is high and ~80% of healthcare costs are related to hospital admissions.

Sodium-glucose cotransporter-2 (SGLT2) inhibitor is considered one of the four foundational therapies (ACE-I or ARNI, beta-blockers, MRA, and SGLT2 inhibitors) for HFrEF. In particular, empagliflozin has been shown in randomized controlled trials to reduce the combined risk of cardiovascular death or HF hospitalization in HF patients with both reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). However, guidelines do not specify the sequence and the timing of which therapy to be commenced. The timing of SGLT inhibitors initiation in the treatment of acute HF is not established. In particular, new-onset acute HF is a group which is understudied in the major trials to date. This study aims to evaluate the efficacy and safety of in-hospital initiation of empagliflozin in patients hospitalized for new onset acute HF, regardless of LVEF for up to 90 days of follow-up.

Inclusion Criteria:

• Subject age >18 hospitalized for primary diagnosis of acute HF

• Dyspnoea (exertional or at rest) and 2 of the following signs: Congestion on chest X-ray; Rales on chest auscultation; Clinically relevant oedema (e.g. ≥1+ on a 0 to 3+ scale); Elevated jugular venous pressure

• Stabilization criteria (while in the hospital): systolic blood pressure ≥100mmHg and no symptoms of hypotension in the preceding 24 hours; No increase in i.v. diuretic dose for 24 h prior; No i.v. vasodilators including nitrates within the last 24 h prior; No i.v. inotropic drugs for 24 h prior

• NT-proBNP ≥1600 pg/mL or BNP ≥400 pg/mL. (Patients with atrial fibrillation: NT-proBNP ≥2400 pg/mL or BNP

  ≥600 pg/mL. Measured during index hospitalization

• Heart failure hospitalization that requires the treatment of a minimum single dose of 40 mg of i.v.

furosemide( or Equivalent i.v loop diuretics defined as 20 mg of torsemide or 1mg of bumetanide)

Exclusion Criteria:

• Cardiogenic shock
• Documented history of HF with previous HF admission
• Current hospitalization for acute HF primarily triggered by pulmonary embolism, cerebrovascular accident, or acute myocardial infraction
• Interventions in the past 30 days prior or planned during the study: Major cardiac surgery, or Transcatheter aortic valve implantation (TAVI), or percutaneous coronary intervention (PCI), or MitraClip; Implantation of cardiac resynchronization therapy device; Cardiac mechanical support implantation
• Current or expected heart transplant, left ventricular assist device (LVAD), intraaortic balloon pumping (IABP), or patients with planned inotropic support in an outpatient setting
• Haemodynamically severe uncorrected primary cardiac valvular disease planned for surgery or intervention during the course of the study
• eGFR <20 mL/min/1.73m2 as measured during index hospitalization (latest measurement before randomization) or patients requiring dialysis
• Type 1 diabetes mellitus (DM)
• History of ketoacidosis, including diabetic ketoacidosis
• Current or prior treatment with SGLT2 inhibitors in the 90 days prior to enrolment.