FlexNav EU CE Mark Study

Assessment of the Abbott FlexNav™ Delivery System for Portico Transcatheter Aortic Valve Implantation in High and Extreme Risk Patients With Symptomatic Severe Aortic Stenosis

The purpose of this clinical investigation is to characterize the safety of the next-generation FlexNav™ Delivery System for transfemoral implantation of the Portico™ Transcatheter Aortic Heart Valve in symptomatic severe aortic stenosis patients who are considered of high or extreme risk for surgical aortic valve replacement. Data from the study will be used to support CE Mark of the FlexNav™ Delivery System and Loading System in Europe.

The FlexNav European Union (EU) study will be conducted as a prospective, multi-center, single-arm investigational study.

High or extreme risk patients with symptomatic, severe native aortic stenosis who are determined by an independent subject selection committee to meet eligibility criteria for Portico™ Transcatheter Aortic Heart Valve implantation via a transfemoral access approach will undergo a Portico valve implant using the next-generation FlexNav Delivery System.

Subject data will be collected at screening, baseline, pre-procedure, peri-procedure, post-procedure, discharge, 30 days, 6 months and 1-year from the index procedure.

Inclusion Criteria:

- Candidates for High Risk classification must meet all the following inclusion criteria:

1. Subjects must have co-morbidities such that the local heart team concur the predicted risk of operative mortality is ≥15% or a minimum Society of Thoracic Surgeons (STS) score of 8%.

   a) A candidate who does not meet the STS score criteria of ≥ 8% may be included in the study if at least one surgeon in the local heart team concludes and documents the patient's predicted risk of operative mortality is ≥15%. The surgeon's assessment of operative comorbidities (including frailty indices) not captured by the STS score must be documented in the study case report form as well as in the patient medical record.

2. Subject is of legal age or older for consent in the host country.

3. Subject has senile degenerative aortic valve stenosis with echo-derived criteria: mean gradient >40 mmHg or jet velocity greater than 4.0 m/s or doppler velocity index (DVI) <0.25 and an initial aortic valve area (AVA) of ≤1.0 cm2 (indexed Effective Orifice Area (EOA) ≤ 0.6 cm2/m2). (Qualifying AVA baseline measurement must be within 60 days prior to informed consent).

4. Subject has symptomatic aortic stenosis as demonstrated by NYHA Functional Classification of II, III, or IV.

5. The subject 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.

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

7. Subject's aortic annulus is 19-27mm diameter as measured by computed tomography (CT) conducted within 12 months prior to informed consent. If a CT i contraindicated and/or not possible to be obtained for certain subjects, a 3D echo and non-contrast CT of chest and abdomen/pelvis may be accepted.

   All candidates for Extreme Risk classification must meet # 2, 3, 4, 5, 6, 7 of the above criteria, and

8. After formal consultation with the local heart team (including at least one surgeon) it is agreed that medical factors preclude the subject from undergoing 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%. The local heart teams' consult notes shall specify the medical or anatomic factors leading to that conclusion and include a printout of the calculation of the STS score to additionally identify the risks in these patients.

Exclusion Criteria:

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

1. Evidence of an acute myocardial infarction (defined as: ST Segment Elevation as evidenced on 12 Lead ECG) within 30 days prior to index procedure.
2. Aortic valve is a congenital unicuspid or congenital bicuspid valve, or is noncalcified as verified by echocardiography.
3. Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation 3-4+).
4. Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior to index procedure.
5. Pre-existing prosthetic heart valve or other implant in any valve position, prosthetic ring, severe circumferential mitral annular calcification (MAC) which is continuous with calcium in the LVOT, severe (greater than 3+) mitral insufficiency, or severe mitral stenosis with pulmonary compromise.
6. Blood dyscrasias as defined: leukopenia (WBC<3000 mm3), acute anemia (Hb < 9 g/dL), thrombocytopenia (platelet count <50,000 cells/mm³).
7. History of bleeding diathesis or coagulopathy.
8. Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support.
9. Untreated clinically significant coronary artery disease requiring revascularization.
10. Hemodynamic instability requiring inotropic support or mechanical heart assistance.
11. Need for emergency surgery for any reason.
12. Hypertrophic cardiomyopathy with or without obstruction (HOCM).
13. Severe ventricular dysfunction with left ventricular ejection fraction (LVEF) <20% as measured by resting echocardiogram.
14. Echocardiographic evidence of intracardiac mass, thrombus or vegetation.
15. Active peptic ulcer or upper GI bleeding within 3 months prior to index procedure.
16. A known hypersensitivity or contraindication to aspirin, heparin, ticlopidine (Ticlid), or clopidogrel (Plavix), or sensitivity to contrast media which cannot be adequately premedicated.
17. Recent (within 6 months prior to index procedure date) cerebrovascular accident (CVA) or a transient ischemic attack (TIA).
18. Renal insufficiency (creatinine > 3.0 mg/dL) and/or end stage renal disease requiring chronic dialysis.
19. Life expectancy < 12 months from the time of informed consent due to noncardiac co-morbid conditions.
20. Significant aortic disease, including abdominal aortic or thoracic aneurysm defined as maximal luminal diameter 5cm or greater; 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.
21. Native aortic annulus size < 19 mm or > 27 mm per the baseline diagnostic imaging.
22. Aortic root angulation > 70°.
23. Currently participating in an investigational drug or device study.
24. Active bacterial endocarditis within 6 months prior to the index procedure.
25. Bulky calcified aortic valve leaflets in close proximity to coronary ostia.
26. Non-calcified aortic annulus.
27. Iliofemoral vessel characteristics that would preclude safe insertion of the FlexNav™ delivery system with or without an arterial introducer sheath such as severe obstructive calcification, or severe tortuosity.
28. In the judgment of the investigator, a condition that could limit a patient's ability or willingness to participate in the study, comply with study required testing and/or follow- up visits or that could impact scientific integrity of the study.