LVAD Versus GDMT in Ambulatory Advanced Heart Failure Patients

Inclusion Criteria:

1. All patients ≥18 years,

2. End-stage heart failure, evaluated by the local Heart Team, defined as:

• Left ventricular ejection fraction ≤ 35% within 1 week prior to randomizationand

• Cardiac Index < 2.2 L/min/m² by hemodynamic use within 1 month prior torandomization or VO2 max < 14 ml/kg/min (or <50% of predicted VO2max) within 1month prior to randomization OR low 6-min walking test (< 420 m) within 1 monthprior to randomization or ≥ 2 hospitalizations for heart failure in the pastyear and

• NYHA III-IV (INTERMACS profile 4-6) and and

• Receiving medical management with optimal doses of betablockers,Angiotensin-Converting-Enzyme-inhibitors or Angiotensin II Receptor Blockers orangiotensin receptor neprilysin inhibitor (if eligible) and MineralocorticoidReceptor Antagonists and Sodium-GLucose co-Transporter-2 (SGLT2) inhibitors forat least 45 days if tolerated according to guideline at maximal tolerated dose (if maximal HF drug dosage is not reached the investigators will have toexplain reason behind not maximal dosage).

• Receiving Cardiac Resynchronization Therapy and or Implantable CardioverterDefibrillators if indicated for at least 45 days and

• No mechanical circulatory support or inotrope therapy since > 30 days,

3. Having a health coverage,

4. Signed written informed consent,

5. Patient without any legal protection measure.

Exclusion Criteria:

1. Inotrope dependent patients or existence of ongoing mechanical circulatory support (MCS) in the last 30 days,

2. Right ventricular dysfunction (heart team consensus) with the expected need ofBi-VAD support,

3. Female patients currently pregnant or women of childbearing age who were not usingcontraception,

4. Active infection,

5. Irreversible end-organ dysfunction prior to LVAD implantation,

6. Contraindication to anti-coagulant or anti-platelet therapies,

7. History of any organ transplant prior to inclusion,

8. Psychiatric disease/disorder, irreversible cognitive dysfunction or psychosocialissues likely to impair compliance,

9. Frailty according to heart team,

10. Platelet count < 100,000 x 103/liter (<100,000/ml)

11. Body Surface Area (BSA) < 1.2 m2,

12. Any condition other than heart failure that could limit survival to less than 24months,

13. Chronic renal insufficiency (GFR definitely <30 ml/min) or hepatic cirrhosis,

14. Participation in any other interventional clinical investigation.