The Assessment of Partial Guideline-Directed Medical Therapy Down Titration in Heart Failure in Remission.

Inclusion criteria

• Signed and dated written informed consent prior to randomization
• Age ≥ 18 years
• Prior diagnosis of heart failure with reduced ejection fraction (left ventricular ejection fraction < 40%)
• Heart failure remission (defined as a quantified improvement in LVEF to ≥50% or described as a "normalized" or "recovered" LVEF on echocardiography or cardiac MRI at least 6 months prior; a normal LVESVi and LVEF during screening; no residual functional limitations caused by heart failure; a NT-proBNP < 250 pg/mL during screening)
• Treatment with at least three heart failure therapies (ACE inhibitors, angiotensin-receptor blockers, angiotensin receptor-neprilysin inhibitors, mineralocorticoid receptor antagonists, or sodium-glucose cotransporter-2 inhibitors), consistent with international heart failure guidelines, at maximally tolerated dose and stable for at least 6 months before screening.

Exclusion criteria

• Severe kidney disease: chronic kidney disease with significant albuminuria, defined as an eGFR (creatinine or cystatin C-based using the 2021 CKD-EPI formula) < 60 mL/min/1,73m2 and a urine-albumine creatinine ratio ≥ 200 mg/g, or requiring dialysis, or a history of kidney transplantation.
• Recent major cardiovascular events, including acute coronary syndromes, coronary artery bypass surgery, stroke, or TIA, in the 90 days before screening.
• Uncontrolled hypertension, defined as a systolic blood pressure above 160 mmHg and/or a diastolic blood pressure above 100 mmHg despite three antihypertensive agents, assessed during a 24-hour blood pressure measurement during screening.
• Atrial fibrillation or atrial flutter with a resting heart rate > 110 beats per minute during screening
• Suboptimal biventricular pacing in those treated with cardiac synchronization therapy, defined as a biventricular pacing percentage under 98% during screening.
• Any concomitant current or future class I indication for the use SGLT2i beside heart failure: diabetes mellitus type II with ASCVD, or at least two major risk factors (i.e., obesity, hypertension, smoking, dyslipidemia or albuminuria) during screening.
• Any sustained ventricular arrhythmias in the six months before screening.
• Any untreated valvular heart disease of moderate or greater severity during screening.
• Presence of any other disease with a life expectancy of less than two years.
• Pregnant or lactating women.