"TARGET 2.0 Study": Safety and Performance of the Cardiovalve TR Replacement System

Inclusion Criteria:

1. Subject is ≥ 18 and <85 years

2. Severe tricuspid regurgitation (TR) ≥3+ based upon echocardiography, as assessed byindependent core laboratory using a 5-grade classification (mild (1), moderate (2),severe (3), massive (4), torrential (5)). Trace and no TR is considered 0)29

3. Symptomatic, NYHA Class II-IV

4. Left ventricular ejection fraction (LVEF) ≥ 30%

5. Subject adequately treated based upon medical standards

6. Subjects are at high risk for open heart surgery

7. Subject provided written, informed consent before investigation enrollment

8. Subject approved by the Subject Screening Committee Anatomical Inclusion Criteria (measured by CT)

9. Right femoral vein diameter > 9mm

10. Tricuspid valve diameter < 55 mm

11. RV length > 45 mm

Exclusion Criteria:

Subjects will be excluded from the investigation if fulfill any of the following criteria:

1. Cardiac anatomy deemed not suitable for the Cardiovalve TR system as evaluated (byCT)

2. Venous peripheral anatomy or any spinal anatomy that is unsuitable for CardiovalveTR implant delivery (by CT)

3. Primary tricuspid disease that may interfere with Cardiovalve implantation

4. Severe right ventricular failure (by Echo core lab adjudication)

5. Significant coronary artery disease requiring percutaneous or surgical intervention

6. Severe systolic pulmonary arterial pressure, pASP > 2/3 systemic BP with PVR > 5Wood units after vasodilator challenge

7. Presence of any known life threatening non-cardiac disease that will limit thesubject's life expectancy to less than one year

8. Cerebrovascular event (stroke, TIA) within the past 3 months

9. Active endocarditis or history of mitral/tricuspid endocarditis within 3 months orinfection requiring antibiotic within 2 weeks before index procedure

10. Subject has significant other sided valvular heart disease which requires treatment (e.g. mitral regurgitation or stenosis, or aortic regurgitation or stenosis)

11. Documented primary coagulopathy or platelet disorder, including thrombocytopenia (absolute platelet count <90k)

12. Documented evidence of significant renal dysfunction (eGFR<30 ml/min/1.73m2) or anyform of dialysis at time of screening within 30 days

13. Untreatable hypersensitivity or contraindication to any of the following: allantiplatelets, all anticoagulants, nitinol alloys (nickel and titanium), bovinetissue, glutaraldehyde, contrast media, or Polyethylene Glycol (PEG)

14. Subjects unsuitable for implantation due to thrombosis of the lower venous system orpresence of a vena cava filter

15. Evidence of an acute myocardial infarction (AMI) ≤ 1 month (30 days)

16. Liver cirrhosis > Child-Pugh Class A

17. Psychiatric or behavioral disease including known alcohol or drug abuser that islikely to impair compliance with protocol

18. Pregnant, lactating or planning pregnancy within next 12 months

19. Requirement for antibiotic treatment within the last 48 hours

20. Surgical or interventional procedure planned within 30 days prior to index procedure

21. Refractory heart failure requiring advanced intervention (i.e. left ventricularassist device, transplantation) or UNOS Status 1 heart transplant or priororthotropic heart transplantation.

22. Prior Tricuspid valve surgery or transcatheter tricuspid valve procedure that mayinterfere with the Cardiovalve device. Valve in a valve procedure is excluded.

23. Modified Rankin Scale > 4 disability

24. Implant or revision of any rhythm management device (CRT or CRT-D) or implantablecardioverter-defibrillator within 30 days prior to index procedure

25. Acutely decompensated heart failure (i.e. hemodynamically unstable or requiring IVinotrope) at the time of screening

26. Severe COPD or continuous use of home oxygen

27. Hgb < 9 g/dL at screening

28. The subject has contraindication against a transesophageal echo (TEE) during theprocedure that cannot be replaced by other imaging.

29. Currently participating in an investigational drug or another device investigationwhich has not reached its primary endpoint

30. Subjects with >2 leads or with any lead that may interfere with Cardiovalveprocedure or device