European Clinical Evaluation of the Carmat Total Artificial Heart

Clinical Evaluation of the Carmat Total Artificial Heart for Patients With Advanced Heart Failure

The objective of this clinical investigation is to evaluate the safety and performance of the Carmat Total Artificial Heart (TAH) in subjects with advanced heart failure requiring biventricular support.

Each subject receiving the Carmat TAH will be evaluated at 6 months (180 days) for primary and secondary endpoints with further follow-up assessments up to 2 years.

The results of the study will be used to support a CE mark application.

Center selection is based on the following: experience with VAD/TAH implantation and record of good results in this patient population (% of survival), the infrastructure required to perform the clinical investigation (especially the surgical and cardiology teams); site resources and experience to manage the clinical study and the patient population; the adherence to the standards of Good Clinical Practice. A specific focus during the site selection is done on dedicated VAD - nurse team to ensure that:

• Sites are experienced in the selection of patients whom require a mechanical circulatory support. Social and psychological conditions of the patient and family must be considered to ensure patient and family commitment in the care pathway,
• Close supervision of patients on the use of the device (when changing batteries) by experienced hospital professionals is guarantee;
• Extensive hospital training program and regular support for patients and family - relatives are ensured.

Inclusion Criteria:

1. Patient age: 18 to 75 years

2. Inotrope dependent or cardiac Index (CI) < 2.2 L/min/m2 if inotropes are contra-indicated (heart failure due to restrictive or constrictive physiology).

3. On Optimal Medical Management as judged by the investigator based on current Heart Failure practice guidelines (ESC/AHA)

4. Eligible to biventricular Mechanical Circulatory Support according to ISHLT guidelines for mechanical circulatory support:

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

      1. RVEF ≤ 30%
      2. RVSWI ≤ 0.25 mmHg*L/m2
      3. TAPSE ≤ 14mm
      4. RV-to-LV end-diastolic diameter ratio > 0.72
      5. CVP > 15 mmHg
      6. CVP-to-PCWP ratio > 0.63
      7. Tricuspid insufficiency grade 4

   2. Treatment-refractory recurrent and sustained ventricular tachycardia or ventricular fibrillation in the presence of untreatable arrhythmogenic pathologic substrate

   3. Heart failure due to restrictive or constrictive physiology (e.g., hypertrophic cardiomyopathy, cardiac amyloidosis / senile or other infiltrative heart disease)

5. Anatomic compatibility confirmed using 3D imaging (CT-scan)

6. Patient's affiliation to health care insurance, if local requirement

7. Patient has signed the informed consent and committed to follow study requirements

Exclusion Criteria:

1. Body Mass Index (BMI) < 15 or > 47

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

3. Existence of any temporary mechanical circulatory support other than IABP and Impella

4. History of cardiac or other organ transplant

5. Patients who have required cardiopulmonary resuscitation for > 30 minutes within 14 days prior to implant

6. Known intolerance to anticoagulant or antiplatelet therapies

7. Coagulopathy defined by platelets < 100k/μl or INR ≥ 1.5 not due to anticoagulant therapy

8. Cerebro-vascular accident < 3 months or symptomatic or a known > 80% carotid stenosis

9. Known abdominal or thoracic aortic aneurysm > 5 cm

10. End-organ dysfunction as per investigator judgment and following but not limited criteria:

    1. Total bilirubin > 100 μmol/L (5,8 mg/dl) or cirrhosis evidenced by ultrasound, CT-scan or positive biopsy
    2. GFR < 30ml/min/1.73m2

11. History of severe Chronic Obstructive Pulmonary Disease or severe restrictive lung disease

12. Recent blood stream infection (<7 days)

13. Documented amyloid light-chain (AL amyloidosis)

14. Hemodynamically significant peripheral vascular disease accompanied by rest pain or extremity ulceration

15. Illness, other than heart disease, that would limit survival to less than 1 year

16. Irreversible cognitive dysfunction, psychosocial issues or psychiatric disease, likely to impair compliance with the study protocol and TAH management

17. Participation in any other clinical investigation that is likely to confound study results or affect the study

18. Pregnancy or breast feeding (woman in age of childbearing will have to show negative pregnancy test)