Eligibility

All Candidates for this study (Cohorts A and B) must meet the following criteria:

1. Patient has senile degenerative aortic valve stenosis with echocardiographically derived criteria: mean gradient >40 mmHg or jet velocity greater than 4.0 m/s and an initial aortic valve area (AVA) of ≤0.8 cm2 or indexed EOA < 0.5 cm2/m2. Qualifying echo must be within 45 days of the date of the procedure.
2. Patient is symptomatic from his/her aortic valve stenosis, as demonstrated by NYHA Functional Class II or greater.
3. The heart team agrees (and verified in the case review process) that valve implantation will likely benefit the patient.
4. The study patient or the study patient's legal representative has been informed of the nature of the study, agrees to its provisions and has provided written informed consent as approved by the Institutional Review Board (IRB) of the respective clinical site.
5. The study patient agrees to comply with all required post-procedure follow-up visits including annual visits through 5 years and analysis close date visits, which will be conducted as a phone follow-up.

Once eligibility in accordance to the above criteria is established, patients are assessed for operability. Patients who are candidates for AVR must meet the criteria set forth in Section 5.2.4 and patients who are deemed not to be candidates for surgery must meet the criteria set forth in Section 5.2.5. All candidates must meet the above criteria in order to be stratified into Cohort A or Cohort B.

Additional Eligibility Criteria Specific to Cohort A

Inclusion Criteria:

1. STS ≥ 4
2. Heart team (including examining cardiac surgeon) agrees on eligibility including assessment that TAVR or AVR is appropriate
3. Heart team agrees (a priori) on treatment strategy for concomitant coronary disease (if present)
4. Study patient agrees to undergo surgical aortic valve replacement (AVR) - if randomized to control treatment

Exclusion Criteria:

1. Heart Team assessment of inoperability (including examining cardiac surgeon).
2. Evidence of an acute myocardial infarction ≤ 1 month (30 days) before the intended treatment [defined as: Q wave MI, or non-Q wave MI with total CK elevation of CK-MB ≥ twice normal in the presence of MB elevation and/or troponin level elevation (WHO definition)].
3. Aortic valve is a congenital unicuspid or congenital bicuspid valve, or is non-calcified.
4. Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation >3+).
5. Preexisting bioprosthetic valve or ring in any position

6. Complex coronary artery disease:

   1. Unprotected left main coronary artery
   2. Syntax score> 32 (in the absence of prior revascularization)
7. Any therapeutic invasive cardiac procedure resulting in a permanent implant that is performed within 30 days of the index procedure (i.e. PCI). Implantation of a permanent pacemaker is not excluded.
8. Any patient with a balloon valvuloplasty (BAV) within 30 days of the procedure.
9. Leukopenia (WBC < 3000 cell/mL), acute anemia (Hgb < 9 g/dL), Thrombocytopenia (Pit < 50,000 cell/mL).
10. Hypertrophic cardiomyopathy with or without obstruction (HOCM).
11. Severe ventricular dysfunction with LVEF < 20%.
12. Echocardiographic evidence of intracardiac mass. thrombus or vegetation.
13. Active upper GI bleeding within 3 months (90 days) prior to procedure.
14. A known contraindication or hypersensitivity to all anticoagulation regimens, or inability to be anticoagulated for the study procedure.
15. Native aortic annulus size < 18 mm or> 25 mm as measured by echocardiogram.
16. Clinically (by neurologist) or neuroimaging confirmed stroke or transient ischemic attack (TIA) within 6 months (180 days) of the procedure.
17. Renal insufficiency (creatinine> 3.0 mg/dL) and/or renal replacement therapy at the time of screening.
18. Estimated life expectancy < 24 months (730 days) due carcinomas, chronic liver disease, chronic renal disease or chronic end stage pulmonary disease.
19. Expectation that patient will not improve despite treatment of aortic stenosis.
20. 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.
21. It is known that the patient is currently enrolled in The PARTNER Trial or was withdrawn from The PARTNER Trial prior to endpoint analysis.
22. Active bacterial endocarditis within 6 months (180 days) of procedure.
23. Patient refuses aortic valve replacement surgery.

Additional Eligibility Criteria Specific to Cohort B Inclusion Criteria

1. The heart team agrees that medical factors preclude operation, based on a conclusion that the probability of death or serious, irreversible morbidity exceeds the probability of meaningful improvement. Specifically, the probability of death or serious, irreversible morbidity is ≥ 50%.
2. The heart team agrees the patient is likely to benefit from valve replacement.

Exclusion Criteria

Candidates will be excluded from the study if any of the following conditions are present:

1. Evidence of an acute myocardial infarction ≤ 1 month (30 days) before the intended treatment [(defined as: Q wave MI, or non-Q wave MI with total CK elevation of CK-MB ≥ twice normal in the presence of MB elevation and/or troponin level elevation (WHO definition)].
2. Aortic valve is a congenital unicuspid or congenital bicuspid valve, or is non-calcified.
3. Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation >3+).
4. Preexisting bioprosthetic valve or ring in any position.
5. Any therapeutic invasive cardiac procedure resulting in a permanent implant that is performed within 30 days of the index procedure (i.e. PCI) Implantation of a permanent pacemaker is not excluded.
6. Any patient with a balloon valvuloplasty (BAV) within 30 days of the procedure.
7. Leukopenia (WBC < 3000 cell/mL). acute anemia (Hgb < 9 g/dL), Thrombocytopenia (Pit < 50,000 cell/mL).
8. Untreated clinically significant coronary artery disease requiring revascularization.
9. Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of screening evaluation.
10. Need for emergency surgery for any reason.
11. Hypertrophic cardiomyopathy with or without obstruction (HOCM).
12. Severe ventricular dysfunction with LVEF < 20%.
13. Echocardiographic evidence of intracardiac mass, thrombus or vegetation.
14. Active upper GI bleeding within 3 months (90 days) prior to procedure.
15. A known contraindication or hypersensitivity to all anticoagulation regimens, or inability to be anticoagulated for the study procedure.
16. Native aortic annulus size < 18 mm or > 25 mm as measured by echocardiogram.
17. Clinically (by neurologist) or neuroimaging confirmed stroke or transient ischemic attack (TIA) within 6 months (180 days) of the procedure.
18. Renal insufficiency (creatinine> 3.0 mg/dL) and/or renal replacement therapy at the time of screening.
19. Estimated life expectancy < 24 months (730 days) due carcinomas, chronic liver disease, chronic renal disease or chronic end stage pulmonary disease.
20. Expectation that patient will not improve despite treatment of aortic stenosis.
21. Significant aortic disease, including marked tortuosity (hyperacute bend), aortic arch atheroma [especially if thick (> 5 mm), protruding or ulcerated] or narrowing (especially with calcification and surface irregularities) of the abdominal or thoracic aorta, severe "unfolding" and tortuosity of the thoracic aorta.
22. Iliofemoral vessel characteristics that would preclude safe placement of 22F or 24F introducer sheath such as severe obstructive calcification. severe tortuosity or minimum average vessel size less than 7 mm.
23. 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.
24. It is known that the patient is currently enrolled in The PARTNER Trial or was withdrawn from The PARTNER Trial prior to endpoint analysis.
25. Active bacterial endocarditis within 6 months (180 days) of procedure.

Specific Criteria for Nested Registry 1 (NR1) Inclusion: Same criteria as Cohort B Including non-femoral access.

Exclusion: Same criteria as Cohort B.

Specific Criteria for Nested Registry 2 (NR2) Inclusion: Same criteria as Cohort B Including non-femoral access

Exclusion: Same criteria as Cohort B, except for exclusion 22 which is modified (italicized) for NR2 as follows.

• Iliofemoral vessel characteristics that would preclude safe placement of 22F or 24F introducer sheath such as severe obstructive calcification, severe tortuosity or minimum average vessel size less than 6 mm. (see NR 2).

Specific Criteria for Nested Registry 3 (NR3)

Inclusion:

1. Stenosed or insufficient bioprosthetic valve in any position.
2. Annulus measurement 18mm-25mm.

Exclusion:

1. The degenerated xenograft presents with a concomitant perivalvular leak (between prosthesis and native annulus), is not securely fixed in the native annulus or is not structurally intact (e.g. wireform frame fracture).
2. The degenerated xenograft presents with a partially detached leaflet that in the aortic position may obstruct a coronary ostium.
3. The inner diameter of the degenerated xenograft is outside of the measurement requirement for the placement of a 23 or 26mm SAPIEN XT THV.
4. The patient has echocardiographic evidence of intracardiac mass, thrombus or non-valvular vegetation.
5. Patient is multimorbid without appropriate motivation or life expectancy less than 1 year.
6. The patient requires emergency surgery for any reason.
7. The patient has a history of active endocarditis within the past three months.
8. The patient has an active infection requiring current antibiotic therapy (if temporary, enrollment possible 4 weeks after discontinuation of antibiotics).
9. Other xenograft or THV in another position.