The ENCIRCLE Trial

Inclusion Criteria:

1. 18 years of age or older

2. MR ≥ 3+

3. NYHA functional class ≥ II

4. Per the Heart Team, commercially available surgical or transcatheter treatmentoptions are deemed unsuitable due to clinical, anatomic or technical considerations.

5. Subject's heart failure management has been optimized based on subjectcharacteristics and applicable guidelines, and stable for at least 30 days prior toenrollment.

6. The subject or subject's legal representative has been informed of the nature of thestudy, agrees to its provisions and has provided written informed consent.

Exclusion Criteria:

1. Mitral/cardiac anatomy that would preclude appropriate delivery and deployment ofthe SAPIEN M3 dock or valve

2. Inappropriate anatomy for femoral introduction and delivery of the SAPIEN M3 dockand valve

3. Presence of any device that will contact or interfere with the SAPIEN M3 Systemduring delivery or after implantation

4. Left ventricular ejection fraction <25%

5. Severe right ventricular dysfunction

6. Need for aortic, tricuspid or pulmonic valve intervention within the next 12 months

7. History of heart transplant

8. Cardiac imaging evidence of intracardiac mass, thrombus or vegetation

9. Active bacterial endocarditis within 180 days of the procedure

10. Hemodynamic instability requiring inotropic or mechanical support within 30 days ofthe procedure

11. Myocardial infarction within 30 days of the procedure

12. Clinically significant untreated coronary artery disease requiring revascularization

13. Any percutaneous cardiovascular intervention, cardiovascular surgery, or carotidsurgery within 30 days of the procedure

14. Stroke or transient ischemic attack within 90 days of the procedure

15. Irreversible, severe pulmonary hypertension

16. Chronic obstructive pulmonary disease requiring home oxygen therapy or chronicoutpatient oral steroid use

17. Renal insufficiency or receiving renal replacement therapy

18. Liver disease

19. Planned surgery within the next 12 months

20. Inability to tolerate or a medical condition precluding treatment withantithrombotic therapy, including heparin administration during the procedure

21. Active infection requiring current antibiotic therapy

22. Active SARS-CoV-2 infection (Coronavirus-19 [COVID-19]) or previously diagnosed withCOVID-19 with sequelae that could confound endpoint assessments

23. Leukopenia, anemia, thrombocytopenia, history of bleeding diathesis or coagulopathyor hypercoagulable states

24. Refusal of blood products

25. Female who is pregnant or lactating

26. Estimated life expectancy <12 months due to non-cardiac conditions

27. Participating in another investigational drug or device study that has not reachedits primary endpoint

28. Subject considered to be part of a vulnerable population