Safety and Efficacy Study of the Medtronic CoreValve® System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement

Inclusion Criteria:

- Extreme Risk Only: Subject must have comorbidities such that one cardiologist and two
cardiac surgeons agree that medical factors preclude operation, based on a conclusion
that the probability of death or serious morbidity exceeds the probability of
meaningful improvement. Specifically, the predicted operative risk of death or
serious, irreversible morbidity is ≥ 50% at 30 days.

- High Risk Surgical Only: Subject must have comorbidities such that one cardiologist
and two cardiac surgeons agree that predicted risk of operative mortality is ≥15% (and
predicted operative mortality or serious, irreversible morbidity risk of < 50%) at 30
days.

- Subject has senile degenerative aortic valve stenosis with: mean gradient > 40 mmHg,
or jet velocity greater than 4.0 m/sec by either resting or dobutamine stress
echocardiogram, or simultaneous pressure recordings at cardiac catheterization (either
resting or dobutamine stress), AND an initial aortic valve area of ≤ 0.8 cm2 (or
aortic valve area index ≤ 0.5 cm2/m2) by resting echocardiogram or simultaneous
pressure recordings at cardiac catheterization

- Subject is symptomatic from his/her aortic valve stenosis, as demonstrated by New York
Heart Association (NYHA) Functional Class II or greater.

- The subject or the subject's legal representative has been informed of the nature of
the trial, agrees to its provisions and has provided written informed consent as
approved by the IRB of the respective clinical site.

- The subject and the treating physician agree that the subject will return for all
required post-procedure follow-up visits.

Exclusion Criteria:

Clinical

- Evidence of an acute myocardial infarction ≤ 30 days before the intended treatment.

- Any percutaneous coronary or peripheral interventional procedure performed within 30
days prior to the intended treatment. (High Risk Surgical Only: Including bare metal
stents. Additionally, any drug eluting stents placed within 6 months prior to the
index procedure.)

- Blood dyscrasias as defined: leukopenia (WBC < 1000mm3), thrombocytopenia (platelet
count <50,000 cells/mm3), history of bleeding diathesis or coagulopathy.

- Untreated clinically significant coronary artery disease requiring revascularization.

- Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or
mechanical hemodynamic support.

- Need for emergency surgery for any reason.

- Severe ventricular dysfunction with left ventricular ejection fraction (LVEF) < 20% as
measured by resting echocardiogram.

- Recent (within 6 months) cerebrovascular accident (CVA) or transient ischemic attack
(TIA).

- End stage renal disease requiring chronic dialysis or creatinine clearance < 20
cc/min.

- Active Gastrointestinal (GI) bleeding within the past 3 months.

- A known hypersensitivity or contraindication to any of the following which cannot be
adequately pre-medicated:

- Aspirin

- Heparin (HIT/HITTS)

- Bivalirudin (Extreme Risk Only)

- Nitinol (titanium or nickel)

- Ticlopidine and clopidogrel

- Contrast media

- Ongoing sepsis, including active endocarditis.

- Subject refuses a blood transfusion.

- Life expectancy < 12 months due to associated non-cardiac co-morbid conditions.

- Other medical, social, or psychological conditions that in the opinion of an
Investigator precludes the subject from appropriate consent.

- 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).

- Currently participating in an investigational drug or another device trial.

- Symptomatic carotid or vertebral artery disease.

- Subject has been offered surgical aortic valve replacement but declined. (High Risk
Surgical Only)

Anatomical

- Native aortic annulus size < 18 mm or > 29 mm per the baseline diagnostic imaging.

- Pre-existing prosthetic heart valve any position.

- Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant
aortic regurgitation (3-4+)).

- Moderate to severe (3-4+) or severe (4+) mitral or severe (4+) tricuspid
regurgitation.

- Moderate to severe mitral stenosis.

- Hypertrophic obstructive cardiomyopathy.

- New or untreated echocardiographic evidence of intracardiac mass, thrombus or
vegetation.

- Severe basal septal hypertrophy with an outflow gradient.

- Aortic root angulation (angle between plane of aortic valve annulus and horizontal
plane/vertebrae) > 70° (for femoral and left subclavian/axillary access) and > 30°
(for right subclavian/axillary access).

- Ascending aorta diameter > 43 mm if the aortic annulus diameter is 23-29 mm; ascending
aorta diameter > 40 mm if the aortic annulus diameter is 20-23 mm; or an ascending
aorta diameter > 34 mm if the aortic annulus diameter is 18-20 mm.

- Congenital bicuspid or unicuspid valve verified by echocardiography.

- Sinus of valsalva anatomy that would prevent adequate coronary perfusion.

Vascular

- Transarterial access not able to accommodate an 18Fr sheath.