Safety and Efficacy Study of Lotus Valve for Transcatheter Aortic Valve Replacement

Inclusion Criteria:

1. Subject has documented calcific, severe native aortic stenosis with an initial aortic
valve area (AVA) of ≤1.0 cm2 (or AVA index of ≤0.6 cm2/m2) and a mean pressure
gradient >40 mm Hg or jet velocity >4.0 m/s, as measured by echocardiography and/or
invasive hemodynamics

2. Subject has a documented aortic annulus size of ≥18 mm and ≤29 mm based on the
center's assessment of pre-procedure diagnostic imaging (and confirmed by the Case
Review Committee [CRC]) and, for the randomized cohort, is deemed treatable with an
available size of both test and control device. For the U.S. Continued Access Study
cohort the acceptable aortic annulus size is ≥20 mm and ≤27 mm.

3. Subject has symptomatic aortic valve stenosis with New York Heart Association (NYHA)
Functional Class ≥ II

4. There is agreement by the heart team (which must include a site investigator
interventionalist and a site investigator cardiac surgeon) that subject is at high or
extreme operative risk for surgical valve replacement (see note below for definitions
of extreme and high risk, the required level of surgical assessment, and CRC
confirmation) and that TAVR is appropriate. Additionally, subject has at least one of
the following.

- Society of Thoracic Surgeons (STS) score ≥8% -OR-

- If STS <8, subject has at least one of the following conditions: Hostile chest,
porcelain aorta, severe pulmonary hypertension (>60 mmHg), prior chest radiation
therapy, coronary artery bypass graft(s) at risk with re-operation, severe lung
disease (need for supplemental oxygen, forced expiratory volume in 1 second
[FEV1] <50% of predicted, diffusing capacity of the lungs for carbon monoxide
[DLCO] <60%, or other evidence of severe pulmonary dysfunction), neuromuscular
disease that creates risk for mechanical ventilation or rehabilitation after
surgical aortic valve replacement, orthopedic disease that creates risk for
rehabilitation after surgical aortic valve replacement, Childs Class A or B liver
disease (subjects with Childs Class C disease are not eligible for inclusion in
this trial), frailty as indicated by at least one of the following: 5‑meter walk
>6 seconds, Katz Assessment of Daily Living (Katz ADL) score of 3/6 or less, body
mass index <21, wheelchair bound, unable to live independently, age ≥90 years,
other evidence that subject is at high or extreme risk for surgical valve
replacement (CRC must confirm agreement with site heart team that subject meets
high or extreme risk definition)

5. Heart team (which must include a cardiac interventionalist and an experienced cardiac
surgeon) assessment that the subject is likely to benefit from valve replacement.

6. Subject (or legal representative) understands the study requirements and the treatment
procedures, and provides written informed consent.

7. Subject, family member, and/or legal representative agree(s) and subject is capable of
returning to the study hospital for all required scheduled follow up visits.

Note: Extreme operative risk and high operative risk are defined as follows: Extreme
Operative Risk: Predicted operative mortality or serious, irreversible morbidity risk ≥50%
at 30 days; High Operative Risk: Predicted operative mortality or serious, irreversible
morbidity risk ≥15% at 30 days. Risk of operative mortality and morbidity must be assessed
via an in-person evaluation by a center cardiac surgeon and must be confirmed by the CRC
(which must include an experienced cardiac surgeon).

Exclusion Criteria:

1. Subject has a congenital unicuspid or bicuspid aortic valve.

2. Subject has had an acute myocardial infarction (MI) within 30 days prior to the index
procedure (defined as Q-wave MI or non-Q-wave MI with total creatine kinase (CK)
elevation ≥ twice normal in the presence of creatine kinase-myoglobin band (CK-MB)
elevation and/or troponin elevation).

3. Subject has had a cerebrovascular accident or transient ischemic attack within the
past 6 months prior to study enrollment.

4. Subject has end-stage renal disease or has glomerular filtration rate (GFR) <20 (based
on Cockcroft-Gault formula).

5. Subject has a pre-existing prosthetic aortic or mitral valve.

6. Subject has severe (4+) aortic, tricuspid, or mitral regurgitation.

7. Subject has a need for emergency surgery for any reason.

8. Subject has a history of endocarditis within 6 months of index procedure or evidence
of an active systemic infection or sepsis.

9. Subject has echocardiographic evidence of new intra-cardiac mass, vegetation or
intraventricular or paravalvular thrombus requiring intervention.

10. Subject has (hemoglobin) Hgb <9 g/dL, platelet count <50,000 cells/mm3 or >700,000
cells/mm3, or white blood cell count <1,000 cells/mm3.

11. Subject requires chronic anticoagulation therapy after the implant procedure and
cannot be treated with warfarin (other anticoagulants are not permitted in the first
month) for at least 1 month concomitant with either aspirin or clopidogrel.

12. Subject has had a gastrointestinal bleed requiring hospitalization or transfusion
within the past 3 months, or has other clinically significant bleeding diathesis or
coagulopathy that would preclude treatment with required antiplatelet regimen, or will
refuse transfusions.

13. Subject has known hypersensitivity to contrast agents that cannot be adequately
pre-medicated, or has known hypersensitivity to aspirin, all P2Y12 inhibitors,
heparin, nickel, tantalum, titanium, or polyurethanes.

14. Subject has a life expectancy of less than 12 months due to non-cardiac, comorbid
conditions based on the assessment of the investigator at the time of enrollment.

15. Subject has hypertrophic obstructive cardiomyopathy.

16. Subject has any therapeutic invasive cardiac or vascular procedure within 30 days
prior to the index procedure (except for balloon aortic valvuloplasty or pacemaker
implantation, which are allowed).

17. Subject has untreated coronary artery disease, which in the opinion of the treating
physician is clinically significant and requires revascularization.

18. Subject has severe left ventricular dysfunction with ejection fraction <20%.

19. Subject is in cardiogenic shock or has hemodynamic instability requiring inotropic
support or mechanical support devices.

20. Subject has severe vascular disease that would preclude safe access (e.g., aneurysm
with thrombus that cannot be crossed safely, marked tortuosity, significant narrowing
of the abdominal aorta, severe unfolding of the thoracic aorta, or symptomatic carotid
or vertebral disease).

21. Subject has thick (>5 mm) protruding or ulcerated atheroma in the aortic arch

22. Subject has arterial access that is not acceptable for the test and control device
delivery systems as defined in the device Instructions For Use.

23. Subject has current problems with substance abuse (e.g., alcohol, etc.).

24. Subject is participating in another investigational drug or device study that has not
reached its primary endpoint.

25. Subject has untreated conduction system disorder (e.g., Type II second degree
atrioventricular block) that in the opinion of the treating physician is clinically
significant and requires a pacemaker implantation. Enrollment is permissible after
permanent pacemaker implantation.

26. Subject has severe incapacitating dementia.