The ENCIRCLE Trial; SAPIEN M3 System TransCatheter MItral Valve ReplaCement via TransseptaL AccEss

1. 18 years of age or older
2. MR >= 3+ as assessed by the Echo Core Lab (See MAC Registry)
3. NYHA functional class >= II
4. Per the Heart Team, commercially available surgical or transcatheter
treatment options are deemed unsuitable due to clinical, anatomic or technical
considerations.
5. Subject*s heart failure management has been optimized based on subject
characteristics and applicable guidelines, and stable for at least 30 days
prior to enrollment (See Failed TEER Registry)
Note: Subjects who require significant changes to heart failure medication
after enrollment but prior to the procedure must re-stabilize for 30 days to be
eligible.
6. The subject or subject*s legal representative has been informed of the
nature of the study, agrees to its provisions and has provided written informed
consent.

Subjects who had an attempted but failed TEER procedure may be considered for
enrollment if they meet all eligibility criteria except inclusion 5, and do not
meet the following modified exclusion criteria:
10. Hemodynamic instability requiring inotropic or mechanical support within 72
hours of procedure
13. Percutaneous cardiovascular intervention (other than TEER procedure),
cardiovascular surgery, or carotid surgery within 30 days prior to the
procedure

Mitral/cardiac anatomy that would preclude appropriate delivery and deployment
of the dock or valve, including but not limited to:
• Annular dimensions that could potentially increase the risk of paravalvular
leak (as assessed by Computed Tomography [CT] core lab)
• Commissural jet or lateral commissural flail/prolapse that could potentially
increase the risk of paravalvular leak
• Medial commissural flail or prolapse
• Calcification that would interfere with the SAPIEN M3 System during delivery
or after implantation; if potential for interference is uncertain, see MAC
Registry
• Interatrial septum or left atrium not suitable for transcatheter trans-septal
access
• LVEDD >= 75 mm as assessed by Echo core lab
• Sub-valvular anatomy that is unsuitable for dock encircling as assessed by CT
core lab
• Significant risk of LVOT obstruction as assessed by CT core lab
2. Inappropriate anatomy for femoral introduction and delivery of the SAPIEN M3
Dock and Valve
3. Presence of any device that will contact or interfere with the SAPIEN M3
System during delivery or after implantation
4. LVEF < 25% as assessed by Echo core lab
5. Severe right ventricular dysfunction as assessed by Echo core lab
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 of the 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
carotid surgery within 30 days of the procedure; TEER procedures are excluded
regardless of timeframe (See Failed TEER Registry).
14. Stroke or transient ischemic attack within 90 days of the procedure
15. Irreversible, severe pulmonary hypertension (e.g., pulmonary artery
systolic pressure >= 2/3 systemic pressure)
16. Chronic obstructive pulmonary disease (COPD) requiring home oxygen therapy
or chronic outpatient oral steroid use
17. Renal insufficiency (estimated glomerular filtration rate [eGFR] < 30
mL/min/1.73 m2) or receiving renal replacement therapy
18. Liver disease (cirrhosis of the liver [Child-Pugh class B or C])
19. Planned surgery within the next 12 months
20. Inability to tolerate or a medical condition precluding treatment with
antithrombotic (antiplatelet, anticoagulant) therapy, including heparin
administration during the procedure
21. Active infection requiring current antibiotic therapy (if temporary
illness, subject may be a candidate 2 weeks after discontinuation of
antibiotics)
22. Active SARS-CoV-2 infection (Coronavirus-19 [COVID-19]) or previously
diagnosed with COVID-19 with sequelae that could confound endpoint assessments
(as assessed by the Case Review Board)
23. Leukopenia (White Blood Cells < 3000 cells/mL), anemia (Hemoglobin < 9
g/dL), thrombocytopenia (platelet < 50,000 cells/mL), history of bleeding
diathesis or coagulopathy, or 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
reached its primary endpoint
28. Subject considered to be part of a vulnerable population

Subjects who had an attempted but failed TEER procedure may be considered for
enrollment if they meet all eligibility criteria except inclusion 5, and do not
meet the following modified exclusion criteria:
10. Hemodynamic instability requiring inotropic or mechanical support within 72
hours of procedure
13. Percutaneous cardiovascular intervention (other than TEER procedure),
cardiovascular surgery, or carotid surgery within 30 days prior to the procedure
MAC Registry
Subjects with MAC where the impact on delivery and implantation of the SAPIEN
M3 system is uncertain may be considered for enrollment if they meet the
following modified inclusion criterion and all other eligibility criteria:
2. MR >= 3+, moderate MR and moderate MS, or severe MS as assessed by the Echo
Core Lab