Supplemental Methods

INCLUSION/EXCLUSION CRITERIA

Inclusion Criteria

1) Subject must have co-morbidities such that one cardiologist and two cardiac surgeons agree

that medical factors preclude operation, based on the 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.

2) Failed surgical bioprosthetic aortic valve

3) Subject is symptomatic from his/her aortic valve stenosis, as demonstrated by New York

Heart Association (NYHA) Functional Class II or greater.

4) 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.

5) The subject and the treating physician agree that the subject will return for all required post-

procedure follow-up visits.

EXCLUSION CRITERIA

Subjects were NOT eligible for study participation if they met any of the following exclusion

criteria:

Clinical

1. Evidence of an acute myocardial infarction ≤ 30 days before the MCS TAVR procedure.

2. Any percutaneous coronary or peripheral interventional procedure performed within 30 days

prior to the MCS TAVI procedure.

3. Blood dyscrasias as defined: leukopenia (WBC < 1000mm3), thrombocytopenia (platelet

count <50,000 cells/mm3), history of bleeding diathesis or coagulopathy.

4. Untreated clinically significant coronary artery disease requiring revascularization.

5. Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or

mechanical hemodynamic support.

6. Need for emergency surgery for any reason.

7. Severe ventricular dysfunction with left ventricular ejection fraction (LVEF) < 20% as

measured by resting echocardiogram.

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

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

10. A known hypersensitivity or contraindication to all anticoagulation/antiplatelet regimens

(including inability to be anticoagulated for the index procedure), nitinol, or allergic sensitivity to

contrast media which cannot be adequately pre-medicated.

11. Ongoing sepsis, including active endocarditis.

12. Subject refuses a blood transfusion.

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

14. Other medical, social, or psychological conditions that in the opinion of an Investigator

precludes the subject from appropriate consent.

15. 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).

16. Currently participating in an investigational drug or another device study.

17. Symptomatic carotid or vertebral artery disease.

Anatomical

18. Subject has a:

a) native aortic annulus size < 18 mm or > 29 mm per the baseline diagnostic imaging

(Not applicable for TAV in SAV subjects) OR

b) Surgical bioprosthetic annulus <17mm or >29mm

i. Stented SAV per the manufactured labeled inner diameter OR

ii. Stentless SAV per the baseline diagnostic imaging.

19. Pre-existing prosthetic heart valve with a rigid support structure in either the mitral or

pulmonic position:

a. That could affect the implantation or function of the study valve OR

b. The implantation of the study valve could affect the function of the pre-existing

prosthetic heart valve.

20. Moderate to severe mitral stenosis.

21. 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 aortic

bioprosthesis).

22. Hypertrophic obstructive cardiomyopathy.

23. Echocardiographic evidence of new or untreated intracardiac mass, thrombus or vegetation

24. Severe basal septal hypertrophy with an outflow gradient.

25. 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).

26. Ascending aorta that exceeds the maximum diameter for any given native or bioprosthetic

surgical* 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

27. Congenital bicuspid or unicuspid valve verified by echocardiography (Not applicable for TAV

in SAV subjects).

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

29. Degenerated surgical bioprosthesis presents with a significant concomitant perivalvular leak

(between prosthesis 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)

30. Degenerated surgical bioprosthesis presents with a partially detached leaflet that in the

aortic position may obstruct a coronary ostium (ONLY FOR TAV in SAV subjects)

Vascular

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

SECONDARY ENDPOINTS

1) Major Adverse Cardiovascular and Cerebrovascular Event (MACCE)- event rate at 30 days,

6 months, 12 months and annually thereafter up to 5 years.

MACCE is defined as a composite rate of:

all-cause death

myocardial infarction (MI)

all stroke, and

reintervention

2) The occurrence of individual MACCE components at 30 days, 6 months, 12 months and

annually thereafter up to 5 years.

3) Major Adverse Events (MAE) at 30 days, 6 months, 12 months and annually thereafter up to

5 years.

4) Conduction disturbance requiring permanent pacemaker implantation at 30 days, 6 months,

12 months and annually thereafter up to 5 years.

5) Change in NYHA class from baseline at 30 days, 6 months, 12 months and annually

thereafter up to 5 years.

6) Change in distance walked during 6-minute walk test (6MWT) from baseline to 30 days and

baseline to 12 months.

7) Ratio of days alive out of hospital versus total days alive assessed at 12 months follow-up.

8) Quality of Life (QoL) change from baseline at 30 days, 6 months, 12 months and annually

thereafter up to 5 years using the following measures:

Kansas City Cardiomyopathy Questionnaire (KCCQ)

SF-12, and

EuroQoL

9) Echocardiographic assessment of valve performance at discharge, 30 days, 6 months, 12

months and annually thereafter up to 5 years using the following measures:

transvalvular mean gradient

effective orifice area

degree of aortic valve regurgitation (transvalvular and paravalvular)

10) Aortic valve disease hospitalization at 30 days, 6 months, 12 months and annually thereafter

up to 5 years.

11) Cardiovascular deaths and valve-related deaths at 30 days, 6 months, 12 months and

annually thereafter up to 5 years.

12) Strokes (of any severity) and TIAs at 30 days, 6 months, 12 months and annually thereafter

up to 5 years.

13) Index procedure related MAEs

14) Length of index procedure hospital stay

15) Device success defined as follows:

Successful vascular access, delivery and deployment of the device, and successful

retrieval of the delivery system,

Correct position of the device in the proper anatomical location (placement in the

annulus with no impedance on device function),

Intended performance of the prosthetic valve (aortic valve area >1.2 cm2 for 26, 29 and

31mm valves, ≥0.9 cm2 for 23mm valve (by echocardiography using the continuity

equation) and mean aortic valve gradient <20 mmHg or peak velocity <3 m/sec, without

moderate or severe prosthetic valve AR)

o Assessed acutely in a resting state, either within 24-48 hours after the index

procedure or before hospital discharge. This device success criterion is not

applicable for TAV in SAV subjects.

Only one study valve implanted in the proper anatomical location

16) Procedural success, defined as device success and absence of in-hospital MACCE.

17) Evidence of prosthetic valve dysfunction at 30 days, 6 months, 12 months and annually

thereafter up to 5 years

1Supplemental Methods provided as written in the study protocol.

Supplemental Table 1 Serial Echocardiography Findings

All

N=225

Regurgitation

N=50

Stenosis

N=126

Combined

N=49 P value

Mean aortic gradient, mmHg

Baseline, mmHg1 37.7 ± 18.1

(224)

15.3 ± 6.5

(50)

45.4 ± 15.7

(125)

41.1 ± 12.2

(49)

<0.001

30 day, mmHg 17.0 ± 8.8

(200)

13.2 ± 6.9

(44)

18.6 ± 9.8

(112)

16.9 ± 6.7

(44)

0.003

One year, mmHg 16.6 ± 8.9

(119)

15.4 ± 11.0

(21)

17.8 ± 8.6

(65)

15.0 ± 7.7

(33)

0.28

Effective orifice area, cm2

Baseline, mmHg1 1.02 ± 0.61

(216)

1.92 ± 0.69

(45)

0.72 ± 0.22

(122)

0.92 ± 0.37

(49)

<0.001

30 day, mmHg 1.41 ± 0.65

(173)

1.90 ± 0.88

(41)

1.22 ± 0.45

(90)

1.34 ± 0.49

(42)

<0.001

One year, mmHg 1.41 ± 0.62

(93)

1.73 ± 0.91

(19)

1.23 ± 0.37

(50)

1.51 ± 0.65

(24)

0.01

30 Day Total Aortic Regurgitation, N

201 46 113 42

None/trace 138 (68.7) 28 (60.9) 90 (79.6) 20 (47.6) 0.001

Mild 56 (27.9) 15 (32.6) 22 (19.5) 19 (45.2)

Moderate 7 (3.5) 3 (6.5) 1 (0.9) 3 (7.1)

Severe 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

One Year Total Aortic 122 22 67 33

Regurgitation, N

None/trace 82 (67.2) 14 (63.6) 47 (70.1) 21 (63.6) 0.27

Mild 31 (25.4) 3 (13.6) 19 (28.4) 9 (27.3)

Moderate 9 (7.4) 5 (22.7) 1 (1.5) 3 (9.1)

Severe 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

Values are presented as no. (%) or mean ± standard deviation (no.). 1Baseline data are site-reported. All follow-up data are from the

core lab.

Supplemental Figure 1. Study disposition.

Supplemental Figure 2. All-cause mortality by modality of SVF (A), all-cause mortality by SAV

size (B), and all-cause mortality by expected SV-PPM (C) for patients eligible for 1 year follow-

up. SVF: surgical valve failure; SAV: surgical aortic valve; SV-PPM: predicted surgical valve

prosthesis-patient mismatch.

Supplemental Figure 3. New York Heart Association (NYHA) Classification.

Supplemental Figure 4. Composite endpoint of all-cause mortality, rehospitalization, and

reintervention for any reason except residual aortic regurgitation.

Supplemental Figure 5. Degree of total residual aortic regurgitation over time.

Supplemental Figure 6. Quality of life improvement, represented by KCCQ overall summary

score change from baseline. KCCQ: Kansas City Cardiomyopathy Questionnaire.

Supplemental Figure 7. Quality of life improvement as assessed KCCQ improvements (change

from baseline) were stratified by the mechanism of SVF (A), SV-PPM (B), size of the surgical

valve (C), and residual gradient (D). KCCQ: Kansas City Cardiomyopathy Questionnaire; SVF:

Surgical valve failure; SV-PPM: predicted surgical valve prosthesis-patient mismatch.