REPRISE IV: LOTUS Edge Valve System in Intermediate Surgical Risk Subjects
REPRISE IV: LOTUS Edge Valve System in Intermediate Surgical Risk Subjects
REPRISE IV: REpositionable Percutaneous Replacement of Stenotic Aortic Valve through
 Implantation of LOTUS Edge Valve System in IntermediatE Surgical Risk Subjects
To evaluate safety and effectiveness of the LOTUS Edge™ Valve System when used with the
 Lotus™ or iSleeve™ Introducer Sets for transcatheter aortic valve replacement (TAVR) in
 symptomatic subjects with severe aortic stenosis who are considered at intermediate risk for
 surgical valve replacement including those who have a bicuspid native valve.
Inclusion Criteria:

 -  Subject has documented severe aortic stenosis defined as initial AVA ≤1.0 cm2 (or AVA
 index ≤0.6 cm2/m2) AND a mean pressure gradient ≥40 mm Hg OR maximal aortic valve
 velocity ≥4.0 m/s OR Doppler velocity index ≤0.25 as measured by echocardiography
 and/or invasive hemodynamics. Note: In cases of low flow, low gradient aortic stenosis
 with left ventricular dysfunction (ejection fraction <50%), dobutamine can be used to
 assess the grade of aortic stenosis (maximum dobutamine dose of 20 mcg/kg/min
 recommended)c; the subject may be enrolled if echocardiographic criteria are met with
 this augmentation. (IC1)

 -  A subject in the Bicuspid Aortic Valve Nested Registry cohort must have a documented
 Sievers Type 0 or Sievers Type 1 bicuspid aortic valve based on CT assessment and
 confirmed by the CT core lab with hemodynamic parameters that meet the criteria in
 IC1.

 -  Subject has a documented aortic annulus size of ≥20 mm and ≤27 mm based on the
 center's assessment of pre-procedure diagnostic imaging (and confirmed by the Case
 Review Committee [CRC]).

 -  Subject has symptomatic aortic valve stenosis per IC1 definition above with NYHA
 Functional Class ≥ II.

 -  Heart team (which must include an experienced cardiac interventionalist and an
 experienced cardiac surgeon) agrees that the subject is at intermediate risk of
 operative mortality (≥3% and <8% at 30 days based on the Society of Thoracic Surgeons
 [STS] risk score and other clinical comorbidities unmeasured by the risk calculator)
 and TAVR is appropriate. Note: Risk of operative mortality 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).

 -  Heart team agrees that the subject is likely to benefit from valve replacement. IC7.
 Subject (or legal representative) has been informed of the study requirements and the
 treatment procedures, and provides written informed consent.

 -  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.

 -  Subject is expected to be able to take the protocol-required adjunctive pharmacologic
 therapy.

 Exclusion Criteria:

 -  Subject has a unicuspid or bicuspid aortic valve (not applicable to subjects in the
 Bicuspid Nested Registry cohort).

 -  Subjects in the Bicuspid Nested Registry cohort will have a documented Sievers Type 0
 or Sievers Type 1 bicuspid aortic valve based on CT assessment and confirmed by the CT
 core lab. Subjects are not eligible for inclusion in the Bicuspid Nested Registry
 cohort if the maximum diameter of the ascending aorta is >45 mm or if the subject has
 another indication for aortic root replacement. Subjects with a Sievers Type 2
 bicuspid valve are not eligible for enrollment in any study cohort.

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

 -  Subject has had a cerebrovascular accident or transient ischemic attack clinically
 confirmed by a neurologist or neuroimaging within the past 6 months prior to study
 enrollment.

 -  Subject is on renal replacement therapy or has GFR <20 (based on hospital preferred
 method). See AEC1 below if subject is in the CT Imaging Substudy.

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

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

 -  Subject has moderate to severe mitral stenosis (mitral valve area ≤1.5 cm2 and
 diastolic pressure half-time ≥150 ms, Stage C or Dc).

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

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

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

 -  Subject has platelet count <50,000 cells/mm3 or >700,000 cells/mm3, or white blood
 cell count <1,000 cells/mm3.

 -  Subject will refuse transfusions or 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.

 -  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.

 -  Subject has a life expectancy of less than 24 months due to non-cardiac, comorbid
 conditions based on the assessment of the investigator at the time of enrollment.

 -  Subject has hypertrophic cardiomyopathy.

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

 -  Subject has multivessel coronary artery disease with a Syntax score >22, and/or an
 unprotected left main coronary artery.

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

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

 -  Subject has arterial access that is not acceptable for the study device delivery
 system as defined in the device Instructions For Use.

 -  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 thick, protruding,
 ulcerated atheroma in the aortic arch).

 -  Subject has current problems with substance abuse (e.g., alcohol, etc.) that may
 interfere with the subject's participation in this study.

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

 -  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.

 -  Subject has severe incapacitating dementia.