Please select the eligibility criteria that correspond to the clinical trial below.
Title: Transcatheter Aortic Valve Replacement With the Medtronic Transcatheter Aortic Valve Replacement System In Patients at Low Risk for Surgical Aortic Valve Replacement
Brief Summary: The study objective is to demonstrate that the safety and effectiveness of the Medtronic TAVR system as measured by rates of all-cause mortality or disabling stroke at two years is noninferior to SAVR in the treatment of severe aortic stenosis in subjects who have a low predicted risk of operative mortality for SAVR.

The purpose of the expanded use addendum to the Medtronic TAVR in Low Risk Patients Trial protocol is to conclude the randomized phase of the trial and initiate the single-arm, non-randomized, continued access phase of the trial.


Options:
A: Inclusion Criteria:

1. Severe aortic stenosis, defined as follows:

   1. For symptomatic patients:

      Aortic valve area ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2), OR mean gradient ≥40 mmHg, OR Maximal aortic valve velocity ≥4.0 m/sec by transthoracic echocardiography at rest
   2. For asymptomatic patients:

      * Very severe aortic stenosis with an aortic valve area of ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2), AND maximal aortic velocity ≥5.0 m/sec , or mean gradient ≥60 mmHg by transthoracic echocardiography at rest, OR
      * Aortic valve area of ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2), AND a mean gradient ≥40 mmHg or maximal aortic valve velocity ≥4.0 m/sec by transthoracic echocardiography at rest, AND an exercise tolerance test that demonstrates a limited exercise capacity, abnormal BP response, or arrhythmia OR
      * Aortic valve area of ≤1.0 cm2 (or aortic valve area index of ≤0.6 cm2/m2), AND mean gradient ≥40 mmHg, or maximal aortic valve velocity ≥4.0 m/sec by transthoracic echocardiography at rest, AND a left ventricular ejection fraction \<50%.
2. Documented heart team agreement of low risk for SAVR, where low risk is defined as predicted risk of mortality for SAVR \<3% at 30 days per multidisciplinary local heart team assessment.
3. The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits.

Exclusion Criteria:

1. Any condition considered a contraindication for placement of a bioprosthetic valve (eg, subject is indicated for mechanical prosthetic valve).
2. A known hypersensitivity or contraindication to any of the following that cannot be adequately pre-medicated:

   1. aspirin or heparin (HIT/HITTS) and bivalirudin
   2. ticlopidine and clopidogrel
   3. Nitinol (titanium or nickel)
   4. contrast media
3. Blood dyscrasias as defined: leukopenia (WBC \<1000 mm3), thrombocytopenia (platelet count \<50,000 cells/mm3), history of bleeding diathesis or coagulopathy, or hypercoagulable states.
4. Ongoing sepsis, including active endocarditis.
5. Any percutaneous coronary or peripheral interventional procedure with a bare metal stent within 30 days prior to randomization, or drug eluting stent performed within 180 days prior to randomization.
6. Multivessel coronary artery disease with a Syntax score \>22 and/or unprotected left main coronary artery.
7. Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 10 weeks of Heart Team assessment.
8. Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support.
9. Recent (within 2 months of Heart Team assessment) cerebrovascular accident (CVA) or transient ischemic attack (TIA).
10. Gastrointestinal (GI) bleeding that would preclude anticoagulation.
11. Subject refuses a blood transfusion.
12. Severe dementia (resulting in either inability to provide informed consent for the trial/procedure, prevents independent lifestyle outside of a chronic care facility, or will fundamentally complicate rehabilitation from the procedure or compliance with follow-up visits).
13. Estimated life expectancy of less than 24 months due to associated non-cardiac co-morbid conditions.
14. Other medical, social, or psychological conditions that in the opinion of the investigator precludes the subject from appropriate consent or adherence to the protocol required follow-up exams.
15. Currently participating in an investigational drug or another device trial (excluding registries).
16. Evidence of an acute myocardial infarction ≤30 days before the trial procedure due to unstable coronary artery disease (WHO criteria).
17. Need for emergency surgery for any reason.
18. Subject is pregnant or breast feeding.
19. Subject is less than legal age of consent, legally incompetent, or otherwise vulnerable
20. Pre-existing prosthetic heart valve in any position.
21. Severe mitral regurgitation amenable to surgical replacement or repair.
22. Severe tricuspid regurgitation amenable to surgical replacement or repair.
23. Moderate or severe mitral stenosis amenable to surgical replacement or repair.
24. Hypertrophic obstructive cardiomyopathy with left ventricular outflow gradient.
25. Bicuspid aortic valve verified by echocardiography, MDCT, or MRI.
26. Prohibitive left ventricular outflow tract calcification.
27. Sinus of Valsalva diameter unsuitable for placement of the self-expanding bioprosthesis.
28. Aortic annulus diameter of \<18 or \>30 mm.
29. Significant aortopathy requiring ascending aortic replacement.

    For transfemoral or transaxillary (subclavian) access:
30. Access vessel mean diameter \<5.0 mm for Evolut 23R, 26R, or 29R mm TAV, or access vessel mean diameter \<5.5 mm for Evolut 34R mm or Evolut PRO TAV. However, for transaxillary (subclavian) access in patients with a patent LIMA, access vessel mean diameter \<5.5mm for Evolut 23R, 26R, or 29R mm TAV, or access vessel mean diameter \<6.0 mm for the Evolut 34R or Evolut PRO TAV.
B: Inclusion Criteria Cohort A

1. Patients must have co-morbidities such that the surgeon and cardiologist Co-PIs concur that the predicted risk of operative mortality is ≥15% and/or a minimum STS score of 10
2. Patient has senile degenerative aortic valve stenosis with echocardiographically derived criteria: mean gradient \>40 mmHg or jet velocity greater than 4.0 m/s or an initial aortic valve area of \< 0.8 cm2
3. Patient is symptomatic from his/her aortic valve stenosis, as demonstrated by NYHA Functional Class II or greater
4. The subject or the subject'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 IRB of the respective clinical site
5. The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits

   Cohort B All candidates for Cohort B of this study must meet #2, 3, 4, 5 of the above criteria and
6. The subject, after formal consults by a cardiologist and two cardiovascular surgeons agree 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 should exceed 50%.

Exclusion Criteria

1. Evidence of an acute myocardial infarction ≤ 1month before the intended treatment.
2. Aortic valve is a congenital unicuspid or bicuspid valve; or is non-calcified
3. Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation \>3+).
4. Any therapeutic invasive cardiac procedure performed within 30 days of the index procedure, (or 6 months if the procedure was a drug eluting coronary stent implantation).
5. Pre-existing prosthetic heart valve in any position, prosthetic ring, or severe (greater than 3+) mitral insufficiency.
C: Inclusion Criteria:

* Patients must have severe degenerative aortic valve stenosis (echocardiographic criteria: AV effective orifice area (EOA) of \< 1 cm2, mean AV gradient of \> 40 mmHg, or AV peak systolic velocity of \> 4.0 m/s)
* Patients must be symptomatic from the aortic valve stenosis (dyspnoea in NYHA-class II or greater, angina pectoris, or syncope), or asymptomatic but with echocardiographic evidence of left ventricular hypertrophy, decreased left ventricular ejection fraction, or atrial fibrillation)
* Patients must be 70 years or older
* Patients must be technical and anatomical eligible for both interventions (as specified by Medtronic CoreValve(TM) for the TAVI procedure) after a formal consult by a cardiologist and a cardiovascular surgeon
* Patients must be expected to survive more than one year after the intervention
* Patients must be able to provide written informed consent as approved by the regional ethical committee after having received adequate information about the study
* Patients must be able and agree to return to all post-procedural follow-up visits

Exclusion Criteria:

* Isolated aortic valve insufficiency
* Other significant heart valve disease requiring intervention
* Coronary artery co-morbidity requiring revascularisation
* Any previous open heart surgery
* Myocardial infarction or percutaneous coronary intervention within the last year
* Stroke or TIA within the last 30 days
* Renal insufficiency requiring hemodialysis
* Pulmonary insufficiency (FEV1 or diffusion capacity \< 40% of expected)
* Active infectious disease requiring antibiotics
* Emergency intervention (within 24 hours after the indication for intervention has been made)
* Unstable pre-interventional condition requiring inotropic support or mechanical heart assistance
* A known hypersensitivity or contraindication to heparin or nitinol
* Currently participating in an investigational drug or another device study
D: Inclusion 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 60 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.
6. Study patient agrees to undergo surgical aortic valve replacement (SAVR) - if randomized to control treatment.

Exclusion Criteria

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 mechanical or bioprosthetic valve in any position (except NR3).
5. Any therapeutic invasive cardiac procedure resulting in a permanent implant that is performed within 30 days of the index procedure (unless part of planned strategy for treatment of concomitant coronary artery disease). Implantation of a permanent pacemaker or ICD (S3 Cohort only) is not excluded.
6. Heart team assessment of inoperability (including examining cardiac surgeon).

Answer: A