Carmat Total Artificial Heart As a Bridge to Transplant in Patients with Advanced Heart Failure

Inclusion Criteria:

1. Patient 18 years or older

2. Patient in the waiting list for heart transplant or temporarily contraindicated forheart transplant

3. On inotropes or cardiac Index (CI) < 2.2 L/min/m2

4. On Optimal Medical Management as judged by the investigator based on current HeartFailure practice guidelines (ESC/HAS)

5. Eligible to biventricular Mechanical Circulatory Support according to one of thefollowing category:

6. Biventricular failure with at least two of the following hemodynamic/echocardiographic measurements implying right heart failure:

• RVEF ≤ 30% or FAC < 35%
• RVSWI ≤ 0.25 mmHg*L/m2
• TAPSE ≤ 14mm
• RV-to-LV end-diastolic diameter ratio > 0.72
• CVP > 15 mmHg or persistence of echographic and/or biological signs ofhepatic congestion
• CVP-to-PCWP ratio > 0.63
• PAP index <2
• Tricuspid insufficiency grade 4

2. Treatment-refractory recurrent and sustained ventricular tachycardia orventricular fibrillation in the presence of untreatable arrhythmogenicpathologic substrate.

3. Heart failure due to restrictive or constrictive physiology (e.g., hypertrophiccardiomyopathy, cardiac amyloidosis / senile or other infiltrative heartdisease)

4. Anatomic compatibility confirmed using 3D imaging (CT-scan) and by the screeningcommittee (for Cohort 1).

5. Patient's affiliation to health care insurance

6. Patient has signed the informed consent.

Exclusion Criteria:

1. Absolute contra-indication for heart transplant

2. Existence of any ongoing non-temporary mechanical circulatory support

3. Existence of any ongoing peripheral mechanical circulatory support such as ECMO,Impella (all types), IABP with a support duration > 21 days

4. Patient intubated and unconscious; or intubated and not awake

5. Known intolerance to anticoagulant or antiplatelet therapies or known HeparinInduced Thrombocytopenia.

6. Coagulopathy defined by platelets < 100G/l or INR ≥ 1.5 not due to anticoagulanttherapy.

7. Known thrombophilia (Antithrombin III, protein C or S deficiency) or any recurrentvenous thromboembolic events requiring long term curative oral anticoagulation.

8. Cerebrovascular accident < 3 months or symptomatic (Rankin score >1; Glasgow score <

14. or a known > 80% carotid stenosis.

9. Known abdominal or thoracic aortic aneurysm > 5 cm that has not been treated.

10. Severe end-organ dysfunction as per the following criteria:

11. Total bilirubin > 45 µmol/l (2.65 mg/dl) or cirrhosis evidenced by ultrasound,IRM and positive biopsy

12. GFR < 30ml/min/1.73m2 (with no hemodialysis)

13. History of severe Chronic Obstructive Pulmonary Disease or severe restrictive lungdisease with FEV1/FVC <0.7 and FEV1<50% predicted.

14. Recent active blood stream infection confirmed by a positive hemoculture within 48hours.

15. Documented amyloid light-chain (AL amyloidosis).

16. Hemodynamically significant peripheral vascular disease assessed by clinical exam.

17. Illness, other than heart disease, that would limit survival to less than 2 years.

18. Irreversible cognitive dysfunction, psycho-cognitive disabilities, psycho-socialissues or psychiatric disease, likely to impair compliance with the study protocoland TAH management that in the opinion of the investigator could interfere with theability to manage the therapy (i.e. non-compliance to heart failure therapy,uncontrolled diabetes, mental health issue, etc.).

19. Pregnancy or breast feeding (woman in childbearing age will have to show negativepregnancy test).

20. Patient is currently enrolled or has participated in the last 30 days in anothertherapeutic or interventional clinical study that is likely to confound the studyresults or affect the study.