Digoxin is the oldest, market-authorized drug for heart failure (HF), and very cheap. A large trial with digoxin, the DIG trial, executed in the early nineties revealed a highly significant reduction in HF hospitalizations, but no effect on mortality. A post-hoc analysis of the DIG trial suggests that low serum concentrations of digoxin may not only improve HF hospitalizations but also mortality in chronic HF patients. To confirm these retrospective analyses, a prospective, randomized, placebo-controlled trial is necessary to establish the position of digoxin in the contemporary treatment of HF. Therefore, the investigators examine whether low-level, aiming for serum concentrations 0.5-0.9ng/mL, digoxin is beneficial in HF patients with reduced or mid-range ejection fractions (LVEF <50%).

Inclusion Criteria:

1. Age ≥18year

2. Outpatients with chronic HF, New York Heart Association [NYHA] class II - ambulatory IV

3. LVEF<50%

4. Serum NT-proBNP concentrations:

   Previous HF hospitalization ≤ 1 year before randomisation ≥400pg/mL if sinus rhythm; ≥800pg/mL if AF Previous HF hospitalization > 1 year before randomisation or in the absence of HF hospitalizations ≥ 600pg/mL if sinus rhythm; ≥1000 pg/mL if AF

   BNP concentrations:

   Previous HF hospitalization ≤ 1 year before randomisation ≥100pg/mL if sinus rhythm; ≥200pg/mL if AF Previous HF hospitalization > 1 year before randomisation or in absence of HF hospitalization ≥150pg/mL if sinus rhythm; ≥250pg/mL if AF.

5. ≥14 days stable on guideline-recommended therapy (doses and number of therapies as tolerated by each patient)

Exclusion Criteria:

1. Heart rate ≤60bpm (if sinus rhythm); heart rate ≤70bpm (if AF)
2. History of HF hospitalization ≤7days
3. History of myocardial infarction, myocarditis, percutaneous intervention, RCT, pacemaker/ICD implantation, cardiac surgery or stroke ≤30 days
4. Estimated glomerular filtration rate (eGFR), ≤30ml/min/1.73m2
5. The presence of a mechanical assist device
6. Use of inotropic drugs (dopamine, dobutamine, (nor)adrenaline, and milrinon)
7. Scheduled for mechanical assist device or heart transplant
8. Other non-cardiac conditions with limited life expectancy (≤ duration of the study)
9. Amyloid, hypertrophic obstructive or constrictive cardiomyopathy
10. Accessory atrio-ventricular pathway (e.g. Wolf-Parkinson-White syndrome)
11. (Intermittent) complete heart block or second-degree AV block type Mobitz without pace maker or ICD
12. Severe (grade III/III) aortic valve disease
13. Complex congenital heart disease
14. Proven hypersensitivity to digoxin (prior side effects)
15. Concomitant medication that interacts with digoxin
16. Use of digoxin ≤6 months prior to inclusion
17. Participation in another (intervention) clinical trial (registry studies not included)
18. Women who are pregnant, breastfeeding or may be considering pregnancy during the study period

Double blind, placebo controlled