Partner 3 Study (CPMC, MPMC, ABSMC)

The participants in this study will receive the Edwards SAPIEN 3 transcatheter heart valve replacement (THV) study device. The procedure is referred to as TAVR, or “transcatheter aortic valve replacement.” The device and its delivery system are investigational, which means they are not approved for commercial use by the U.S. Food and Drug Administration (FDA) for patients that have a low risk for complications from surgery. TAVR and the SAPIEN 3 device are FDA-approved for patients who have a high operative risk. However, the FDA is still studying the data on safety and efficacy of TAVR and SAPIEN 3 in low-risk patients and has not yet approved it for these patients. For such patients, the standard method of valve replacement includes open-heart surgery (referred to as “SAVR”—for “surgical aortic valve replacement”).

This study will help provide more data on TAVR in low-risk patients, as well as provide continued access to this procedure while it is still investigational. Your study doctor and staff will explain the risks and potential benefits of TAVR and the standard options open to you. This information is also presented later in this consent form.

The Edwards SAPIEN 3 THV Model 9600TFX study device (S3) is a bioprosthetic heart valve. It is an artificial device made to replace your diseased aortic heart valve. Each valve consists of a stent (mesh tube made of metal) to hold the study device in its intended position and valve leaflets (made of biological material derived from cows) to direct the flow of blood in your heart.

The study device SAPIEN 3 THV with the Commander Delivery System will be implanted transfemorally (through an artery in the leg). Through this route, the study device is delivered by means of a catheter (a long, thin, bendable tube that is placed in a blood vessel) in your leg and then maneuvered through the arteries in your leg leading to your heart to expand (open) your diseased aortic valve.

The study doctor performing the procedure may have limited experience with this technology, but has received extensive training by experienced study doctors who have implanted the study device in patients in the United States, Europe and/or Canada, and by the manufacturer of the study device, Edwards Lifesciences LLC. The risks for the study device and the procedure are listed in the Risk section.

This trial is available at multiple locations:

CPMC (San Francisco)

MPMC (Mills Peninsula- Burlingame)

ABSMC (Alta Bates Summit - Oakland)

Please contact Milena Ferreira FerreiML@sutterhealth.org about study Partner 3

Principal Investigator

David Daniels, MD

Recruitment Information

3 CAP Patients must be covered by Medicare to enable linkage with CMS data for long term follow-up at years 2 through 10

Inclusion:

1. Severe, calcific aortic stenosis as follows:
1. Jet velocity ≥ 4.0 m/s ORmean gradient ≥ 40 mmHg
1. AND
2. AVA ≤ 1.0 cm2ORAVA index ≤ 0.6 cm2/m2
1. AND
3. NYHA ≥ 2 ORexercise test that demonstrates a limited exercise capacity, abnormal BP OR arrhythmia ORasymptomatic with LVEF < 50%
4. Qualifying echo must be within 90 days prior to 4enrollment
2. 2.Heart team agrees the patient has a low risk of operative mortality (STS < 4)
3. 3.The patient has been informed of the nature of the study, agrees to its provisions and has provided written informed consent as approved by the IRB

Exclusion:

1. Native aortic annulus size unsuitable for sizes 20, 23, 26, or 29mm THV based on 3D imaging analysis
2. Iliofemoral vessel characteristics that would preclude safe placement of the introducer sheath
3. MI ≤ 30 Days before enrollment
4. Aortic valve is a unicuspid or bicuspid valve, or non-calcified
5. Severe AR (>3+)
6. Severe MR (>3+) or ≥ moderate stenosis
7. Pre-existing mechanical or bioprosthetic valve in any position (mitral ring is not an exclusion)
8. Complex coronary artery disease:
1. Unprotected left main coronary artery
2. Syntax score > 32 (in the absence of prior revascularization)
3. Heart Team assessment that optimal revascularization cannot be performed
9. Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 30 days of enrollment

10. Leukopenia (WBC < 3000 cell/mL), anemia (Hgb < 9 g/dL), Thrombocytopenia (Plt < 50,000 cell/mL), history of bleeding diathesis, coagulopathy or hypercoagulable states
11. Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of 3enrollment
12. Hypertrophic cardiomyopathy with obstruction (HOCM)
13. Ventricular dysfunction with LVEF < 30%
14. Cardiac imaging (echo, CT, and/or MRI) evidence of intracardiac mass, thrombus or vegetation
15. Inability to tolerate or condition precluding treatment with anti-thrombotic/anticoagulation therapy during or after the valve implant procedure
16. Stroke or TIA within 90 days of enrollment
17. Renal insufficiency (eGFR < 30 ml/min per the Cockcroft-Gault formula) and/or renal replacement therapy
18. Active bacterial endocarditis within 180 days of 4enrollment
19. Severe lung disease (FEV1 < 50% predicted) or currently on home oxygen
20. Severe pulmonary hypertension (e.g., PA systolic pressure ≥ 2/3 systemic pressure)
21. History of cirrhosis or any active liver disease
22. Significant frailty as determined by the Heart Team (after objective assessment of frailty parameters)
23. Significant abdominal or thoracic aortic disease (such as porcelain aorta, aneurysm, severe calcification, aortic coarctation, etc.) that would preclude safe passage of the delivery system or cannulation and aortotomy for SAVR
24. Hostile chest or conditions or complications from prior surgery that preclude safe reoperation (i.e., mediastinitis, radiation damage, abnormal chest wall, adhesion of aorta or IMA to sternum, etc.)
25. Patient refuses blood products
26. BMI > 50 kg/m²
27. Estimated life expectancy < 24 months
28. Absolute contraindication or allergy to iodinated contrast that cannot be adequately treated with pre-medication
29. Currently participating in an investigational drug or another device study. Note: Trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials. Observational studies are not considered exclusionary