Safety & Efficacy Study of the Medtronic CoreValve® System-Treatment of Symptomatic Severe Aortic Stenosis With Significant Comorbidities in Extreme Risk Subjects Who Need Aortic Valve Replacement
Safety & Efficacy Study of the Medtronic CoreValve® System-Treatment of Symptomatic Severe Aortic Stenosis With Significant Comorbidities in Extreme Risk Subjects Who Need Aortic Valve Replacement
To evaluate the safety and efficacy of the Medtronic CoreValve® System for the treatment of
 symptomatic severe aortic stenosis in subjects with significant comorbidities in whom the
 risk of surgical aortic valve replacement has a predicted operative mortality or serious,
 irreversible morbidity risk of ≥50% at 30 days.
The primary objective of the study is to evaluate the safety and effectiveness of the
 Medtronic CoreValve® System (MCS) in a subset of subjects excluded from the U.S. Extreme Risk
 Pivotal Trial population due to one or more additional co-morbidities, as measured by a
 composite of all-cause death or major stroke at 12 months, in the treatment of symptomatic
 severe aortic stenosis in subjects necessitating aortic valve replacement. Subjects enrolled
 in this study have a predicted operative mortality or serious, irreversible morbidity risk of
 ≥50% at 30 days associated with surgical aortic valve replacement.
Inclusion Criteria:

 -  Subject must have co-morbidities 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.

 -  Subjects must meet all of the criteria under at least one of the sub-groups 2a-c:

 a. Senile degenerative aortic valve stenosis and i. At least one of the following
 co-morbid conditions:

 1. Severe (≥3-4+) mitral valve regurgitation as measured by echocardiography

 2. Severe (≥3-4+) tricuspid valve regurgitation as measured by echocardiography

 3. End-stage renal disease requiring renal replacement therapy (Stage 5 of the KDOQI
 CKD Classification) or creatinine clearance <20cc/min but not requiring renal
 replacement therapy

 AND

 ii. mean gradient > 40 mmHg or jet velocity greater than 4.0 m/sec by either
 resting or dobutamine stress echocardiogram (if the LVEF < 50%), or simultaneous
 pressure recordings at cardiac catheterization either resting or with dobutamine
 stress (if the LVEF < 50%) AND iii. 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

 AND/OR

 b. Low gradient, low output aortic stenosis as defined by the presence of all
 three of the following i. In the presence of LVEF <50%, absence of contractile
 reserve, a mean gradient ≥25mmHg and <40mmHg AND jet velocity less than 4.0m/sec
 with dobutamine stress echocardiography or simultaneous pressure recordings at
 cardiac catheterization OR In the presence of LVEF ≥50%, a mean gradient ≥25mmHg
 and <40mmHg AND jet velocity less than 4.0 m/sec, by echocardiography or
 simultaneous pressure recordings at cardiac catheterization AND ii. 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 AND
 iii. radiographic evidence of severe aortic valve calcification AND/OR c. Failed
 bioprosthetic surgical aortic valve

 -  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 study, 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 MCS TAVI procedure.

 -  Any percutaneous coronary or peripheral interventional procedure performed within 30
 days prior to the MCS TAVI 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).

 -  Active Gastrointestinal (GI) bleeding that would preclude anticoagulation.

 -  A known hypersensitivity or contraindication to all anticoagulation/antiplatelet
 regimens (including ability to be anticoagulated for the index procedure), nitinol, or
 [allergic] sensitivity to contrast media which cannot be adequately pre-medicated.

 -  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
 study/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 study.

 -  Symptomatic carotid or vertebral artery disease.

 Anatomical

 Subject has a:

 -  Native aortic annulus size <18 mm or >29 mm per the baseline diagnostic imaging (not
 applicable for TAV in SAV subjects) OR

 -  Surgical bioprosthetic annulus <17mm or >29mm i. Stented SAV per the manufactured
 labeled inner diameter OR ii. Stentless SAV per the baseline diagnostic imaging

 -  Subject has a pre-existing prosthetic heart valve with a rigid support structure in
 either the mitral or pulmonic position:

 1. that could affect the implantation or function of the study valve OR

 2. the implantation of the study valve could affect the function of the pre-existing
 prosthetic heart valve

 -  Moderate to severe mitral stenosis.

 -  Mixed aortic valve disease: aortic stenosis and aortic regurgitation with predominant
 aortic regurgitation, (AR is moderate-severe to severe (≥3-4+))(except for failed
 surgical bioprothesis)

 -  Hypertrophic obstructive cardiomyopathy.

 -  Echocardiographic evidence of new or untreated 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 that exceeds the maximum diameter for any given native or surgical
 bioprosthetic* aortic annulus size (see table below) Aortic Annulus Diameter/
 Ascending Aorta Diameter, 18 mm* - 20 mm/ >34 mm, 20 mm - 23 mm/ >40 mm, 23 mm - 27
 mm/ >43 mm, 27 mm - 29 mm/ >43 mm,

 * 17mm for surgical bioprosthetic aortic annulus

 -  Congenital bicuspid or unicuspid valve verified by echocardiography (Not applicable
 for TAV in SAV subjects).

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

 -  Degenerated surgical bioprothesis presents with a significant concomitant perivalvular
 leak (between prothesis and native annulus), is not securely fixed in the native
 annulus, or is not structurally intact (e.g. wireform frame fracture) (ONLY FOR TAV in
 SAV subjects)

 -  Degenerated surgical bioprothesis presents with a partially detached leaflet that in
 the aortic position may obstruct a coronary ostium (ONLY FOR TAV in SAV subjects)

 Vascular

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