This study will address whether the additional use of Ferric Derisomaltose on top of standard care will improve exercise capacity and quality of life in patients with acute heart failure and iron deficiency. One group of participants will receive treatment with Ferric Derisomaltose and the other group will receive normal saline 0.9% as placebo.

Acute heart failure (AHF) is a very common medical problem. Despite improvements in treatment, many patients suffer limiting exercise capacity and quality of life. Previous comorbidities may account for it. Approximately 80% of patients hospitalized with AHF suffered from a combination of iron deficiency. A decline in exercise capacity may occur under this condition. Some research studies have suggested that giving CHF patients intravenous iron improves symptoms in the short term. It is unknown, however, whether correcting iron deficiency is beneficial to patients with AHF to improve excise capacity and whether it improves quality of life and accelerate recovery from acute duration. This study will help us answer these key questions.

This is an investigator-initiated, randomised, parallel group, double-blind, placebo-controlled trial, evaluating the excise capacity improvement of using ferric derisomaltose versus placebo in hospitalized patients with acute heart failure with reduced ejection fraction before discharge.

Participants will be assessed daily using 6-minute walking test after IV iron injection until discharge from hospital, especially focus on the change from baseline to the 3rd day. Some questionnaires are also conducted to evaluate the self-reported status. Participants will be followed up at 2 weeks and 4 weeks.

The primary and secondary endpoints will be examined in subgroups predefined by baseline variables reflecting demography, Hb level, etiology of HF, left ventricular ejection fraction, natriuretic peptide, index of iron metabolism, eGFR and others.

Inclusion Criteria:

1. Age ≥18 years.

2. Clinical diagnosis of heart failure with reduced ejection fraction (HFrEF), defined as documented 2-dimensional echocardiography left ventricular ejection fraction (LVEF) <50% before randomization.

3. Currently hospitalised for an episode of acute heart failure (AHF) where AHF was the primary reason for hospitalisation, New York Heart Association (NYHA) class II - IV.

4. Reaching hemodynamic stability after standard treatment (if tolerated, initiate four pillars of guideline-directed medical therapies). All of the following (i.e., items a to c) must apply:

   1. Systolic blood pressure≥100mmHg, without symptoms of hypotension;
   2. Stop using intravenous diuretics;
   3. Neither intravenous inotropic drugs or vasodilators were used (including nitrates).

5. Subject is iron deficient defined as serum ferritin <100 ng/mL or 100 ng/mL ≤ serum ferritin ≤299 ng/mL if TSAT <20%.

6. Able and willing to provide informed consent and accomplish 6 minutes-walking test.

Exclusion Criteria:

1. Hematological criteria: ferritin >400 ug/L; hemoglobin <9.0, hemoglobin >13.5 g/dL in women or >14.5 g/dL in men.
2. Renal dialysis or MDRD/CKD-EPI estimated glomerular filtration rate (eGFR) <15ml/min/1.73m2
3. Body weight <35kg at randomization.
4. Heart failure was secondary to valvular diseases or congenital heart diseases.
5. History of acquired iron overload or hemochromatosis (or first-degree relative of hemochromatosis)
6. Known hypersensitivity reaction to any component of ferric derisomaltose (Monofer®) or any of its excipients (water for injections, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment)).
7. Non-iron deficiency anaemia.
8. Already receiving erythropoiesis stimulating agents (ESA) or other iron supplements in previous 4 weeks prior to randomization.
9. Active infection (defined as currently treated with oral or intravenous antibiotics), bleeding (gastrointestinal haemorrhagia, menorrhagia, history of peptic ulcer with no evidence of healing or inflammatory bowel disease) and history of malignant tumor.
10. Any of the following diseases that hinders exercise testing: severe musculoskeletal disease, unstable angina, obstructive cardiomyopathy, severe uncorrected valvular disease, or uncontrolled slow or rapid arrhythmia (mean ventricular rate> 100 beats / min at rest).
11. Known positive HBsAg and/or HCV RNA; known HIV positivity; chronic liver disease (including active hepatitis), hepatic sclerosis, ALT or AST > 3x upper limit of normal.
12. Within 3 months of any of the following: acute myocardial infarction (AMI) or acute coronary syndrome (ACS), transient ischemic attack (TIA) or stroke, uncontrolled hypertension.
13. Revascularization therapy (coronary artery bypass grafting, percutaneous intervention, or major surgery) in the past 3 months; or planning cardiac surgery or revascularization.
14. Baseline 6 minutes-walking distance>500m.
15. Treated with long-term oral high-dose or steroid-immunosuppression therapy.
16. Investigator considers a possible alternative diagnosis to explain the patient's HF symptoms: severe obesity, primary pulmonary hypertension, or chronic obstructive pulmonary disease (COPD).
17. Subject is pregnant (e.g., positive human chorionic gonadotropin test) or breast feeding.
18. Untreated hypothyroidism.
19. Currently enrolled in any other investigational device or drug study <30 days prior to screening, or received other investigational agent(s).