Medtronic CoreValve™ Evolut™ PRO System China Clinical Study
Phase: NA
Conditions: Severe, Symptomatic Aortic Stenosis
Sponsor: Medtronic Cardiovascular

COVER PAGE 
Study Official Title: Medtronic CoreValve™ Evolut™ PRO System China 
Clinical Study (Evolut PRO China Clinical Study) 
NCT Number: NCT04982588 
Document Type: Clinical Investigation Plan / Study Protocol 
Document Date: 13-July-2022 

Medtronic CoreValveTM EvolutTM PRO System China Clinical Study  
Clinical Investigation Plan  
 
MDT18065EVR009 
Version 4.0  13-JUL-2022 
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Clinical Investigation Plan (CIP) 
Protocol No.:  
MDT18065EVR009 
Clinical Trial Protocol: 
Medtronic CoreValve™ Evolut™ PRO System China Clinical Study 
(Evolut PRO China Clinical Study)  
Name of the investigational 
medical device:  
Medtronic CoreValve™ Evolut™ PRO System 
Model/ 
specification: 
The Medtronic CoreValve™ Evolut™ PRO System is comprised of the following three 
components: 
1. CoreValve™ Evolut™ PRO Transcatheter Aortic Valve (TAV) 
2. EnVeo™ PRO Delivery Catheter System (DCS)  
3. EnVeo™ PRO Loading System (LS) 
Component / 
Material 
Model Number/ 
Customer Facing 
Number (CFN) 
Size 
Aortic Annulus 
Diameter (mm) 
CoreValve™ Evolut™ 
PRO TAV 
EVOLUTPRO-23-US 
23 mm 
18 – 20  
EVOLUTPRO-26-US 
26 mm 
20 – 23 
EVOLUTPRO-29-US 
29 mm 
23 – 26 
EnVeo™ PRO Delivery 
Catheter System 
(16eFr) 
ENVPRO-16-US 
20 Fr (Outer 
diameter) 
Not applicable 
EnVeo™ PRO Loading 
System (16eFr) 
L-ENVPRO-1623-US 
Compatible 
with 23 mm 
TAV 
Not applicable 
L-ENVPRO-16-US 
Compatible 
with 26 and 
29 mm TAVs 
Not applicable 
Category of investigational 
medical device: 
Class III 
Class III medical devices 
requiring clinical trial approval: 
Yes 
 No 
 
Similar product in China: 
Yes 
 None
 
Protocol version No. and date:  
Version 4.0, 13-JUL-2022 
Leading Site Clinical trial 
institution: 
The Second Affiliated Hospital of Zhejiang University School of 
Medicine 
Leading Site Investigator: 
Professor Wang Jianan 
Co-Investigators:  
Professor Chen Mao 
The West China hospital 
Sponsor: 
Medtronic CoreValve LLC  

Medtronic CoreValveTM EvolutTM PRO System China Clinical Study  
Clinical Investigation Plan  
 
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Local Sponsor (Agency): 
Medtronic (Shanghai) Management Co., Ltd 
 
 
Confidentiality Statement 
The information contained in this document is confidential and the proprietary property of 
Medtronic. Any distribution, copying, or disclosure without the prior written authorization of 
Medtronic is strictly prohibited. Persons to whom the information is disclosed must know that it is 
confidential and that it may not be further disclosed by them. 
 
 
 

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Clinical Investigation Plan  
 
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1. Investigator’s Statement 
Study Product Name 
The Medtronic CoreValve™ Evolut™ PRO System is comprised of the 
following three components: 
1. CoreValve™ Evolut™ PRO Transcatheter Aortic Valve (TAV) 
2. EnVeo™ PRO Delivery Catheter System (DCS)  
3. EnVeo™ PRO Loading System (LS) 
Sponsor 
Medtronic CoreValve LLC 
Local Sponsor/Agent 
Medtronic (Shanghai) Management Co., Ltd 
Clinical Investigation Plan 
Identifier 
MDT18065EVR009 
Version Number/Date  
Version 4.0, 13-JUL-2022 
I agree that: 
1. I will conduct this clinical trial in strict compliance with the Declaration of Helsinki, current laws and 
regulations of China, and the requirements of the Clinical Investigation Plan; 
2. I will record all required data accurately on the Case Report Form (CRF) and assist to complete the 
final report of the clinical investigation; 
3. The investigational medical device will be used only for this clinical trial and the receipt and use of 
the investigational medical device will be recorded completely and accurately and the records will be 
retained during the process of the clinical investigation; 
4. The monitor and auditor authorized or designated by the Sponsor and the regulatory authorities 
are allowed to conduct monitoring, audit and inspection for the clinical investigation; 
5. The clinical investigation should be conducted in strict compliance with contract/articles of 
agreement signed by all parties. 
I have already read the clinical study protocol, including the above statement and I fully agree all the 
above requirements. 
Investigator’s Signature: 
 
Investigator’s Name: 
 
Institution: 
 
Date:  
 
 
 

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Comments of the Sponsor   
 
Signature (Stamp): 
 
Date: MM/DD/YYYY 
 
 
 
 
 
 
Comments of the Investigator: 
 
Signature: 
     
Date: MM/DD/YYYY 
 
Comments of Medical Device Clinical Trial Institution 
 
Signature (Stamp): 
 
Date: MM/DD/YYYY 

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Table of Contents  
1. 
Investigator’s Statement ................................................................................................. 3 
Table of Contents ...................................................................................................................... 5 
2. 
Sponsor’s information .................................................................................................... 11 
2.1. Name of Sponsor ................................................................................................................... 11 
2.2. Address of Sponsor ................................................................................................................ 11 
2.3. Contact of Sponsor................................................................................................................. 11 
2.4. Relevant qualification document(s) of the Sponsor ................................................................... 11 
2.5. Name, address, contact information and relevant qualification document(s) of local 
sponsor(agency) ........................................................................................................................... 11 
3. 
Glossary .......................................................................................................................... 12 
4. 
Synopsis ......................................................................................................................... 15 
5. 
Objectives and contents of clinical trial ......................................................................... 17 
5.1. Objectives ............................................................................................................................. 17 
5.2. Contents................................................................................................................................ 17 
5.3. Study Organization ................................................................................................................. 17 
6. 
Background information of the clinical trial .................................................................. 18 
7. 
Characteristics, structure and composition, operating principle, mechanism of action 
and range of trial of the investigational product .................................................................... 20 
7.1. Characteristics of the investigational product ........................................................................... 20 
7.2. Structure and composition, operating principle and mechanism of action of the investigational 
product 21 
7.2.1. 
Evolut PRO Transcatheter Aortic Valve (TAV) Prosthesis ..................................................... 21 
7.2.2. 
EnVeo PRO Delivery Catheter System with InLine Sheath ................................................... 22 
7.2.3. 
EnVeo PRO Loading System .............................................................................................. 22 
7.2.4. 
Manufacturer ................................................................................................................... 23 
7.2.5. 
Packaging ........................................................................................................................ 23 
7.2.6. 
Equipment ....................................................................................................................... 24 
7.3. Study trial .............................................................................................................................. 24 
8. 
Indications, contraindications and precautions of the investigational product ............ 24 
9. 
Overall design ................................................................................................................ 24 
9.1. Study design .......................................................................................................................... 24 

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9.1.1. 
Study objectives and/or Endpoints..................................................................................... 25 
9.1.1.1. Study Objective(s) ............................................................................................................ 25 
9.1.1.2. Primary Endpoints ............................................................................................................ 25 
9.1.1.3. Secondary Endpoints ........................................................................................................ 25 
9.1.1.4. Other Outcome Measures ................................................................................................. 26 
9.1.2. 
Selection of study method and rationale ............................................................................ 27 
9.1.3. 
Measures for reducing and avoiding deviation .................................................................... 27 
9.1.4. 
Investigational medical device and controlled medical device/diagnosis-therapeutic method 
(if any) 27 
9.1.5. 
Selection of subjects (including selection of control group if necessary) ............................... 28 
9.1.5.1. Inclusion criteria............................................................................................................... 28 
9.1.5.2. Exclusion criteria .............................................................................................................. 28 
9.1.5.3. Criteria and procedures for trial/treatment termination ....................................................... 30 
9.1.5.4. Time of enrollment ........................................................................................................... 30 
9.1.5.5. Estimated duration of clinical trial and the reasons for determination ................................... 30 
9.1.5.6. Estimated participation duration of each subject................................................................. 30 
9.1.5.7. Number of subjects required for clinical trial ...................................................................... 30 
9.1.6. 
Efficacy evaluation method ............................................................................................... 31 
9.1.6.1. Description of the efficacy parameters ............................................................................... 31 
9.1.6.2. Selection of method and time for evaluation, recording and analysis of the efficacy 
parameters ................................................................................................................................... 31 
9.1.7. 
Safety evaluation method ................................................................................................. 31 
9.1.7.1. Description of the safety parameters ................................................................................. 31 
9.1.7.2. Selection of methods and time for the evaluation, recording and analysis of the safety 
parameters ................................................................................................................................... 31 
9.2. Trial procedures ..................................................................................................................... 32 
9.2.1. 
Study Site Investigative Team Members ............................................................................ 32 
9.2.2. 
Trial flow chart ................................................................................................................. 34 
9.2.3. 
Subject Screening and Enrollment ..................................................................................... 34 
9.2.3.1. Heart Team Risk Assessment ............................................................................................ 37 
9.2.4. 
Required Evaluations ........................................................................................................ 37 
9.2.5. 
Recording Data ................................................................................................................ 41 

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9.2.6. 
Subject Withdrawal or Discontinuation ............................................................................... 43 
9.2.7. 
Norms for using device ..................................................................................................... 44 
9.2.7.1. Product and Study Training Requirements ......................................................................... 44 
9.2.7.2. Product Receipt and Tracking ............................................................................................ 44 
9.2.7.3. Product Storage ............................................................................................................... 45 
9.2.7.4. Product Accountability ...................................................................................................... 45 
9.2.7.5. Product Return ................................................................................................................. 45 
9.2.7.6. Device Malfunction or Explant ........................................................................................... 46 
9.3. Monitoring plan ...................................................................................................................... 46 
10. 
Statistical consideration ................................................................................................ 46 
10.1. 
Statistical design, method and analysis procedures ............................................................. 46 
10.1.1. Primary Endpoint Analyses ................................................................................................ 48 
10.1.2. Secondary Endpoint Analyses ............................................................................................ 48 
10.2. 
Calculation of sample size ................................................................................................. 48 
10.2.1. Total sample size ............................................................................................................. 48 
10.2.2. Case number for each disease in clinical trial and reasons for determination ........................ 49 
10.2.3. Minimum and maximum number of subjects for each clinical trial institution in multicenter 
clinical trial ................................................................................................................................... 49 
10.3. 
Significance level and study power of clinical trial ............................................................... 49 
10.4. 
Estimated drop-out rate .................................................................................................... 49 
10.5. 
Criteria for acceptability/unacceptability of clinical trial results ............................................. 49 
10.6. 
Criteria and reasons for trial termination based on statistics ................................................ 49 
10.7. 
Statistical methods for all data, and processing of missing, unused, wrong (including 
withdrawal and drop out) or abnormal data .................................................................................... 50 
10.8. 
Reporting of procedure deviations from the original statistical plan ...................................... 50 
10.9. 
Criteria for selection of the subjects for analysis set and reasons ......................................... 50 
10.10. 
Exclusion of special information during assumption validation and reasons thereof (if 
applicable) .................................................................................................................................... 50 
11. 
Data management .......................................................................................................... 51 
11.1. 
Data Collection ................................................................................................................. 51 
11.1.1. Electronic Case Report Forms (eCRFs) ............................................................................... 51 
11.1.2. Subject Questionnaires ..................................................................................................... 51 

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11.1.3. Time Windows For Completion and Submission of eCRFs .................................................... 51 
11.1.4. Data Review and Processing ............................................................................................. 51 
12. 
Feasibility analysis ......................................................................................................... 52 
12.1. 
Probability analysis of success ........................................................................................... 52 
12.2. 
Probability analysis of failure ............................................................................................. 52 
13. 
Risks and Benefits .......................................................................................................... 52 
13.1. 
Potential Risks .................................................................................................................. 52 
13.2. 
Potential Benefits ............................................................................................................. 55 
13.3. 
Risk-Benefit Rationale ....................................................................................................... 55 
14. 
Quality control of clinical trial ........................................................................................ 56 
15. 
Ethical issues and informed consent of clinical trial ...................................................... 56 
15.1. 
Ethical considerations ....................................................................................................... 56 
15.1.1. Statement of Compliance .................................................................................................. 56 
15.1.2. Investigator’s Responsibilities ............................................................................................ 57 
15.2. 
Examination and approval of study protocol ....................................................................... 59 
15.3. 
Informed consent process and informed consent form ........................................................ 60 
16. 
Provisions for reporting of adverse event and equipment deficiencies......................... 61 
16.1. 
Adverse event (AE) .......................................................................................................... 61 
16.2. 
Serious adverse event (SAE) ............................................................................................. 62 
16.3. 
Device Deficiency (DD) ..................................................................................................... 63 
16.4. 
Causality Assessment ....................................................................................................... 63 
16.5. 
Anticipated or Unanticipated ............................................................................................. 64 
16.6. 
Evaluation and Documentation of Adverse Events .............................................................. 64 
16.7. 
Reporting procedures and information of contact ............................................................... 66 
16.7.1. Reporting of Adverse Events ............................................................................................. 66 
16.7.2. Notification of Adverse Events ........................................................................................... 67 
16.7.3. Expedited Safety Reporting Requirements .......................................................................... 67 
17. 
Provisions for clinical study protocol deviation and the revision of clinical study 
protocol ................................................................................................................................... 71 
17.1. 
Protocol Deviations ........................................................................................................... 71 
17.2. 
Revisions or Amendments to the Clinical Investigational Plan .............................................. 72 
18. 
Record Retention ........................................................................................................... 72 

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19. 
Suspension or Early Termination ................................................................................... 73 
19.1. 
Investigational Center Suspension or Termination .............................................................. 73 
19.2. 
Subject Follow-Up In Case of Termination .......................................................................... 73 
20. 
Direct access to source data/documents ....................................................................... 74 
20.1. 
Investigator Records ........................................................................................................ 74 
20.2. 
Investigator Reporting Responsibilities ............................................................................... 75 
20.3. 
Audits and Inspections ..................................................................................................... 75 
21. 
Finance and insurance ................................................................................................... 76 
21.1. 
Clinical Investigation Agreement ....................................................................................... 76 
22. 
Contents included in the clinical study report ............................................................... 77 
23. 
Confidentiality principle ................................................................................................. 77 
24. 
Agreement on trial results publication .......................................................................... 77 
25. 
Responsibilities of all parties ......................................................................................... 78 
26. 
Data Review Committees ............................................................................................... 78 
26.1. 
Clinical Events Committee ................................................................................................. 78 
27. 
Appendices ..................................................................................................................... 78 
APPENDIX I: NAMES AND ADDRESSES OF INVESTIGATIONAL CENTERS .............................. 79 
APPENDIX II: ECHOCARDIOGRAPHY PROCEDURES .............................................................. 80 
APPENDIX III: MULTI-SLICE COMPUTED TOMOGRAPHY ACQUISTION GUIDELINES ........... 93 
APPENDIX IV: STS CALCULATOR AND RISK FACTORS ......................................................... 100 
APPENDIX V: DEFINITIONS: SAFETY ENDPOINTS AND EFFICACY EVENTS ......................... 102 
APPENDIX VI: STUDY CONTACTS ......................................................................................... 113 
APPENDIX VII: SAMPLE INFORMED CONSENT FORM .......................................................... 114 
28. 
Version History ............................................................................................................. 115 
29. 
References ................................................................................................................... 117 
 
List of Tables 
Table 1. The Evolut PRO System Components ..........................................................21 
Table 2. Summary of Site Key Study Personnel ........................................................33 
Table 3. Summary of visit schedule and required evaluations ..................................40 

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Table 4. Non-reportable medical occurrences associated with index implant 
procedure ..................................................................................................................65 
Table 5. Investigator Reporting Requirements for AE and Device Deficiencies ........68 
Table 6. Sponsor Reporting Requirements for AE and Device Deficiencies ...............68 
Table 7. Investigator Reporting Requirements .........................................................75 
Table 8. Parameters for evaluation of the severity of aortic regurgitation ...............88 
Table 9. Parameters for evaluation of the severity of mitral regurgitation ...............89 
Table 10. Parameters for evaluation of the severity of tricuspid regurgitation ........89 
Table 11.Recommended scan parameters ................................................................94 
 
 
List of Figures 
Figure 1. Study organization .....................................................................................18 
Figure 2. Medtronic CoreValve™ Evolut™ PRO System Components .........................23 
Figure 3. Study flow chart .........................................................................................34 
Figure 4. Flow chart of the study entry process ........................................................37 
Figure 5. Analysis sets for the study endpoints.........................................................47 
Figure 6. Left ventricular outflow tract (LVOT) diameter measurements .................84 
Figure 7. LVOT velocity recording .............................................................................85 
Figure 8. Aortic valve velocities ................................................................................86 
Figure 9. Left ventricle and left atrium measurements .............................................90 
Figure 10. Example images in original orientation (axial, coronal, and sagittal) ......95 
Figure 11. Example images of reformatted oblique coronal, oblique sagittal, double 
oblique axial, and 3D reconstruction ........................................................................96 
Figure 12. Aortic annulus measurements..................................................................97 
Figure 13. Examples of Sinus of Valsalva diameters .................................................98 
Figure 14. Examples of Sinus of Valsalva heights .....................................................99 
 

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2. Sponsor’s information 
2.1. Name of Sponsor 
Medtronic CoreValve LLC   
2.2. Address of Sponsor 
 
  
2.3. Contact of Sponsor 
The contact of Sponsor will be provided separately in the Investigational Site File (ISF).  
2.4. Relevant qualification document(s) of the Sponsor 
Relevant qualification document(s) of the sponsor will be provided under a separate cover. 
2.5. Name, address, contact information and relevant 
qualification document(s) of local sponsor(agency) 
Medtronic (Shanghai) Management Co., Ltd 
  
 
 
 
 
 
Relevant qualification document(s) of the sponsor will be provided under a separate cover. 
 
 

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3. Glossary  
Term/Acronym 
Definition 
2D 
Two-dimensional  
3D 
Three-dimensional 
ADE 
Adverse device effect 
AE 
Adverse event 
AOA 
Alpha-amino oleic acid 
AR 
Aortic regurgitation 
AS 
Aortic stenosis 
AVA 
Aortic valve area 
AVAI 
Aortic valve area index 
AVR 
Aortic valve replacement 
BAV 
Balloon aortic valvuloplasty  
BSA 
Body surface area 
CEC 
Clinical Events Committee 
CI 
Confidence interval 
CIP 
Clinical Investigation Plan 
CMDE 
Center for Medical Device Evaluation 
CT 
Computed tomography 
CVA 
Cerebrovascular accident 
DCS 
Delivery catheter system  
DD 
Device deficiency 
DVI 
Doppler velocity index 
EC 
Ethics Committee  
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EOA 
Effective orifice area 
EOAI 
Effective orifice area index 
ERC 
Eligibility Review Committee 
FDA 
(United States) Food and Drug Administration 
GCP 
Good clinical practice 
GI 
Gastrointestinal  
HIT/HITTS 
Heparin-Induced Thrombocytopenia / Heparin-Induced Thrombocytopenia and 
Thrombosis  
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 

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Term/Acronym 
Definition 
IFU 
Instructions for Use 
ILS 
EnVeo™ InLine Sheath 
IMA 
Internal mammary artery 
LBBB 
Left bundle branch block 
LIMA 
Left internal mammary artery 
LLC 
Limited liability company 
LS 
Loading system  
LTFU 
Lost-To-Follow-Up 
LV 
Left ventricle 
LVEF 
Left ventricular ejection fraction 
LVOT 
Left ventricular outflow tract 
MDCT/MSCT 
Multi-detector computer/computed tomography or Multi-slice 
computer/computed tomography 
MGV2 
Mean gradient across aortic valve 
MI 
Myocardial infarction 
mRS 
Modified Rankin score 
NMPA 
National Medical Product Administration  
NYHA 
New York Heart Association  
PCI 
Percutaneous coronary intervention  
PI 
Principal Investigator 
PROM 
Predicted risk of mortality 
PW 
Pulsed wave 
QoL 
Quality of Life  
RBBB 
Right bundle branch block  
SADE 
Serious adverse device effect 
SAE 
Serious adverse event 
SAVR 
Surgical aortic valve replacement 
SDV 
Source data verification 
STS 
Society of Thoracic Surgeons  
TAV 
Transcatheter aortic valve  
TAVI 
Transcatheter aortic valve implantation 
TAVR 
Transcatheter aortic valve replacement  
TEE 
Transesophageal echocardiology 
TIA 
Transient ischemic attack 
TR 
Tricuspid regurgitation 
TTE 
Transthoracic echocardiography /echocardiogram 

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Term/Acronym 
Definition 
TVT-R 
Transcatheter Valve Therapy Registry 
 
 
USADE 
Unanticipated serious adverse device effect 
V2 
Valve velocity 
VARC II 
Valve Academic Research Consortium II 
VTI 
Velocity time integral 
WBC 
White blood cell 
 
 
 

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4. Synopsis 
Title 
The Medtronic CoreValve™ Evolut™ PRO System (Transcatheter Aortic Valve 
Replacement-TAVR) Clinical Study in China (Evolut PRO China Clinical Study) 
Clinical Study 
Type 
Pivotal/Phase III, interventional study 
Study Design 
Prospective, single arm, multi-center, interventional, pre-market 
Product Name 
The Medtronic CoreValve™ Evolut™ PRO System is comprised of the following 
three components: 
1. CoreValve™ Evolut™ PRO Transcatheter Aortic Valve (TAV) 
2. EnVeo™ PRO Delivery Catheter System (DCS)  
3. EnVeo™ PRO Loading System (LS) 
Sponsor  
Medtronic CoreValve LLC  
 
Local Sponsor 
Medtronic (Shanghai) Management Co., Ltd 
  
 
Indication under 
investigation  
Severe, symptomatic aortic stenosis 
Product Status 
Investigational; the Evolut PRO System (TAV, DCS and LS) involved in this study 
are labeled “Clinical trial use only” (i.e., investigational device labeling) 
 
Note: Effective 24-DEC-2021, National Medical Products Administration (NMPA) 
approved the Medtronic CoreValve™ Evolut™ PRO System for the treatment of 
severe aortic stenosis for symptomatic patients in China who are at high or 
extreme risk for open heart surgery. Overseas clinical data were utilized to 
support product registration. The Evolut PRO System will be commercially 
available during the Evolut PRO China Clinical Study enrollment period. However, 
only Evolut PRO System components that are labeled investigational will be used 
in the study. Commercial Evolut PRO System components will not be used in the 
study.  
Study Objective 
To evaluate the safety and efficacy of the Medtronic CoreValve™ Evolut™ PRO 
System when used by China implanting centers in Chinese patients with severe 
symptomatic aortic stenosis (AS) who are at high risk for Surgical Aortic Valve 
Replacement (SAVR). 
Primary 
Endpoints 
Safety 
All-cause mortality at 30 days 
Efficacy 

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• 
Percentage (%) of evaluable echocardiograms with moderate or severe 
aortic regurgitation at 30 days 
Secondary 
Endpoints 
Safety 
• 
1) The VARC II1 Combined Safety Endpoint at 30 days, which includes the 
following components: 
• 
All-cause mortality 
• 
All stroke (disabling and non-disabling) 
• 
Life-threatening bleeding 
• 
Acute kidney injury: stage 2 or 3 (including renal replacement therapy) 
• 
Coronary artery obstruction requiring intervention 
• 
Major vascular complication 
• 
Valve-related dysfunction requiring repeat procedure (BAV, TAVI, or 
SAVR)  
• 
2) Event rates of the individual components of the VARC II composite safety 
endpoint at 30 days 
• 
3) New permanent pacemaker at 30 days 
Efficacy 
• 
4) Device success at 24 hours to 7 days per VARC II1  
• 
5) Valve performance parameters at 30 days by transthoracic 
echocardiography (TTE): 
• 
Mean aortic gradient 
• 
Effective orifice area 
• 
Degree of aortic regurgitation (transvalvular, paravalvular, total) 
Number of 
Centers 
Targeting 6 centers with a maximum of 8 centers in China 
Sample Size 
Estimating 65 subjects with a maximum of up to 70 subjects in China with an 
attempted implant, comprised of the following: 
• 
1) Primary study population: 50 subjects with an attempted implant using 
the Evolut PRO system 
• 
2) Roll-in population:  The first two attempted subjects at each site will be 
considered “roll-in” subjects.  The maximum number of roll-in subjects 
among all sites will be 20 subjects.  The roll-in population will be followed 
per the same protocol as the primary study population; however, results 
from the roll-in population will be analyzed separately from the primary 
study population. 
Key Inclusion/ 
Exclusion Criteria 
Key inclusion criteria: 
1. Aortic valve area (AVA) < 1.0 cm2 (or indexed AVA <0.6 cm2/m2) OR 
mean gradient > 40 mmHg, OR max aortic velocity > 4.0 m/sec 

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2. High risk for SAVR defined as STS-PROM score ≥ 8% AND ≤ 15%, OR 
documented Heart Team agreement of high risk for AVR due to frailty or 
comorbidities 
3. Symptoms of aortic stenosis and NYHA ≥ II 
Key exclusion criteria: 
1. Age is less than 65 years old  
2. Non‐calcified aortic valve  
3. Bicuspid aortic valve with no raphe or 2 raphes (Sievers classification 
type 0 or type 2)2 
4. Ascending aortic diameter > 4.5 cm 
Study Procedures 
and Assessments 
• 
Clinical assessment at pre and post-procedure, discharge, 30 days, 6 
months, 1 year, and annually through 5 years  
• 
Transthoracic echocardiogram (TTE) at pre and post-procedure, 30 days, 
1 year, and annually through 5 years  
• 
Multi-Detector Computed Tomography (MDCT) at pre-procedure  
• 
12-lead ECG at pre-procedure and 30 days  
• 
EQ-5D Quality of Life (QoL) at pre-procedure, 30 days and 1 year 
 
5. Objectives and contents of clinical trial 
5.1. Objectives 
The objective of this study is to evaluate the safety and efficacy of the Medtronic CoreValve™ Evolut™ 
PRO System when used by China implanting centers in Chinese patients with severe symptomatic aortic 
stenosis (AS) who are at high risk for Surgical Aortic Valve Replacement (SAVR).   
5.2. Contents 
This is a prospective, single arm, multi-center, interventional, pre-market study. The study is targeting 6 
centers with a maximum of 8 centers in China.  The study is estimating 65 subjects with a maximum of 
up to 70 subjects with attempted implants in this study. The primary endpoints are all-cause mortality 
and the percentage of evaluable echocardiograms with moderate or severe prosthetic aortic valve 
regurgitation at 30 Days. Subjects will be followed up through five-year post-implantation. 
5.3. Study Organization 
This multi-center clinical study will be conducted at the investigational sites including the leading site. 
Several vendors, core laboratories and committees will be established to provide independent review of 
the data or assessment of study parameters based on the services they provide. A Data Review 
Committee will comprise of the leading site Principal Investigator (PI) and the authorized data 

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management/biostatistics. Additionally, the study sponsor will oversee the execution and management 
of study. An overview of the study stakeholders and organization is provided in Figure 1. 
 
 
Figure 1. Study organization 
6. Background information of the clinical trial  
Over the past ten years, transcatheter aortic valve replacement (TAVR) has emerged as a transformative 
technology for the management of severe aortic stenosis.  TAVR has become the standard of care for 
patients with aortic stenosis who are inoperable or at extreme risk for surgical aortic valve replacement 
(SAVR) and is the preferred alternative for patients with severe aortic stenosis who are at high risk for 
SAVR.  Following Cribier’s3 first implantation in 2002, TAVR has evolved to become a standard procedure 
at specialized heart centers worldwide and is now performed with only moderate sedation rather than 
general anesthesia in many patients. 
The Medtronic CoreValve self-expanding TAVR system received the CE Mark in 2007, and the United 
States Food and Drug Administration (FDA) approvals for Extreme Risk and High Risk patient populations 
in 2014.  There is extensive published experience demonstrating the CoreValve system is fulfilling its 
Monitoring (Medtronic Core Clinical 
Solutions) 

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intended role with a favorable risk/benefit ratio, and rigorous clinical trials have established its safety 
and effectiveness, with improved mortality rate and quality of life compared with medical therapy in 
extreme risk patients,4 and even superiority to SAVR among high operative risk patients.5 
While there have been significant improvements in TAVR outcomes due to better patient selection, 
increasing operator experience, and iterations in device technology, important issues remain.  Clinical 
challenges where further advances would be desirable include the occurrence of major procedural 
complications6,7,8, stroke9,10, paravalvular aortic regurgitation11,12, vascular complications13,14, and need 
for new permanent pacemaker implantation15,16,17,18.  
To this end, Medtronic developed modifications to the CoreValve frame and delivery catheter system to 
enable resheathing or full recapture of the device before it is released from the delivery system.  These 
modifications are incorporated in the CoreValve™ Evolut™ R system (hereafter “Evolut R”).  The ability 
to resheath or recapture the device allows the operator to reposition or remove the bioprosthesis if the 
initial implant positioning is sub-optimal (too high or too low).  This feature is desirable in that it 
facilitates accurate final positioning which has been shown to mitigate risks associated with sub-optimal 
positioning such as paravalvular leak19,20, acute migration8, and AV-conduction disturbance related to 
implant depth15.  In addition, the EnVeo™ PRO Delivery Catheter System with EnVeo™ InLine Sheath 
provides physicians the option to use a lower profile introducer sheath, which may reduce the risk for 
major vascular complications. 
A comprehensive protocol of bench and animal testing of the Evolut R system has demonstrated its 
functionality and has confirmed that changes to enable recapture have not impacted the structural 
integrity, hydrodynamic performance, or durability of the CoreValve bioprosthesis.  Beginning in 
October 2013, clinical studies of the Evolut 23R, 26R and 29R valve sizes involving 301 patients have 
been conducted in Australia, New Zealand, Europe, and the United States.  These clinical studies confirm 
that TAVR with the Evolut R system can be performed with an acceptable incidence of procedural and 
device-related complications, that short term safety and clinical efficacy of the Evolut R system are 
similar to the predicate CoreValve system, and there are no new safety risks associated with the use of 
the resheath/recapture feature.  Results from these studies21 were used to gain the CE Mark in August 
2014 for the 23R valve size and February 2015 for the Evolut 26R and 29R valve sizes, and FDA approval 
in June of 2015 for the Evolut 23R, 26R and 29R sizes.  
In order to further improve the performance of the Evolut R system with respect to paravalvular 
regurgitation, the Evolut R valve was modified.  Specifically, an outer wrap of porcine pericardial tissue 
was added to cover the first 1.5 cells of the inflow aspect of the frame.  The intent of the tissue wrap is 
to provide a larger surface area contact between the frame and native annulus, intended to improve 
annular sealing and reduce the potential for paravalvular regurgitation.  This iteration of the Evolut R 
system is known as the Medtronic CoreValve™ Evolut™ PRO system (referred to as the “Evolut PRO 
system”). 
In 2016, a 60-patient pre-market clinical study of the Evolut PRO systemi in the United States 
demonstrated a reduction in the occurrence of moderate or severe paravalvular regurgitation and an 
acceptable safety profile consistent with Evolut R system.  Data from this study was used to obtain FDA 
approval in March 2017, and CE Marking in July 2017.  Intermediate risk approval was received by FDA in 
 
i The Evolut PRO system was initially labeled in the pre-market US clinical study as “Medtronic TAVR 2.0.”  The TAVR 2.0 devices are identical to 
the Evolut PRO models proposed for use in the clinical trial in China. 

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July 2017 and CE Marking August 2016. In addition, in September 2018, the United States FDA approved 
the removal of a precaution statement in the Evolut PRO labeling relating to the use of the Evolut PRO 
system in patients with bicuspid aortic valves who are at intermediate, high, or extreme risk for SAVR.  
This approval was based on clinical data from the Society of Thoracic Surgery/American College of 
Cardiology Transcatheter Valve Registry (TVT-R) from the commercial experience of the Evolut R and 
Evolut PRO systems in a post-market real-world environment that reported acceptable clinical outcomes 
in patients with bicuspid aortic valves and at increased risk for SAVR.22  
Therefore, the objective of this clinical study is to confirm that the established safety and efficacy of the 
Evolut PRO System, inclusive of the system component models outlined in Section 7.1, can be replicated 
by Chinese implanting centers in Chinese patients with severe symptomatic aortic stenosis, inclusive of 
both tricuspid and bicuspid anatomy (Sievers classification type 1), who are deemed at high risk for 
SAVR. Data from this study may be used to support license registration for new generation(s) or 
expanded indication(s) of the study devices in China. 
7. Characteristics, structure and composition, operating principle, 
mechanism of action and range of trial of the investigational 
product 
For overview of the Medtronic CoreValve™ Evolut™ PRO System, see also the Investigator’s Brochure 
(IB) which includes preclinical testing and clinical data of this investigational product.  
7.1. Characteristics of the investigational product 
The Medtronic CoreValve™Evolut™ PRO System (hereafter “Evolut PRO system”) is a recapturable 
transcatheter aortic valve replacement (TAVR) system comprised of the following three components:  
1. CoreValve™ Evolut™ PRO Transcatheter Aortic Valve (TAV): 23 mm, 26 mm, 29 mm sizes 
2. EnVeo™ PRO Delivery Catheter System (DCS)  
3. EnVeo™ PRO Loading System (LS) 
These components are provided separately for the procedure. A listing of the system components is 
provided in Table 1. All components are provided sterile and are intended for single use only. The 
CoreValve™ Evolut™ PRO TAV is loaded into the delivery catheter system using the loading system 
immediately prior to implantation. 
The Evolut PRO TAV is intended as a permanent implant throughout the patient’s life unless there is 
clinical indication to replace it with another prosthetic valve. The delivery catheter system is in contact 
with the body only during the device introduction and deployment phase of the implant procedure, 
typically less than 90 minutes. 
 
 

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Table 1. The Evolut PRO System Components 
Component / 
Material 
Description 
Model Number/ 
Customer Facing 
Number (CFN) 
Size 
Aortic Annulus 
Diameter (mm) 
CoreValve™ 
Evolut™ PRO 
TAV 
The bioprosthetic valve 
manufactured by suturing 
valve leaflets and skirt, 
made from porcine 
pericardium, onto a self-
expanding nitinol frame. 
There are three sizes: 
23mm, 26mm, and 29mm. 
EVOLUTPRO-23-US 
23 mm 
18 – 20  
EVOLUTPRO-26-US 
26 mm 
20 – 23 
EVOLUTPRO-29-US 
29 mm 
23 – 26 
EnVeo™ PRO 
Delivery 
Catheter 
System (16Fr 
Equivalent) 
TAV is loaded onto the 
distal end of DCS, 
introduced through the 
arterial vasculature to the 
stenotic native aortic valve, 
and percutaneously 
delivered and implanted. 
There is one size of DCS.  
ENVPRO-16-US 
20 Fr (Outer 
diameter) 
Not applicable 
EnVeo™ PRO 
Loading System 
(16Fr 
Equivalent) 
Supports loading of a TAV 
onto the distal end of DCS. 
There are two sizes of LS: 
23mm and 26/29mm. 
L-ENVPRO-1623-US 
Compatible with 
23 mm TAV 
Not applicable 
L-ENVPRO-16-US 
Compatible with 
26 and 29 mm 
TAVs 
Not applicable 
 
7.2. Structure and composition, operating principle and 
mechanism of action of the investigational product 
7.2.1. 
Evolut PRO Transcatheter Aortic Valve (TAV) Prosthesis 
The transcatheter aortic valve (TAV) is a single-use, implantable device. The Evolut PRO TAV is available 
in three sizes (23 mm, 26 mm and 29 mm), covering an aortic annulus diameter of 18 to 26 mm  
(Table 1). The TAV is comprised of three leaflets and a sealing skirt constructed from glutaraldehyde-
fixated porcine pericardium, sewn to a compressible and self-expandable Nitinol support frame  
(Figure 2A). An outer wrap made of porcine pericardium, the same material as the inner skirt and 
leaflets, covers the external frame on the first 1.5 cells of the inflow. The TAV is processed with an anti-
mineralization treatment of alpha-amino oleic acid (AOA), a compound derived from oleic acid, a 
naturally occurring long-chain fatty acid. 

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7.2.2. 
EnVeo PRO Delivery Catheter System with InLine Sheath 
The delivery catheter system facilitates the placement of the TAV within the annulus of the aortic valve 
(Figure 2C). The catheter assembly is flexible and compatible with a 0.035 in (0.889 mm) guidewire. The 
distal (deployment) end of the system features an atraumatic, radiopaque catheter tip and a capsule 
that covers and maintains the bioprosthesis in a crimped position. The capsule includes a distal flare to 
enable full recapture of the bioprosthesis after partial deployment. A stability layer is fixed at the handle 
and extends down the outside of the catheter shaft. It provides a barrier between the retractable 
catheter and the introducer sheath and vessel walls, thus enabling the catheter to retract freely. 
The EnVeo InLine Sheath (ILS) is assembled over the stability layer, which functions as a hemostatic 
introducer sheath and minimizes the access site size to the capsule diameter. The InLine Sheath is 
compatible with a 20 Fr introducer. 
The delivery catheter system consists of a catheter with an integrated handle to provide the user with 
accurate and controlled deployment. The handle is on the proximal end of the catheter and is used to 
load, deploy, recapture, and reposition the bioprosthesis. The handle features a gray front grip used to 
stabilize the system. The blue actuator turns to deploy the bioprosthesis precisely. Arrows on the 
actuator indicate the direction of rotation required to deploy the bioprosthesis. If desired, the blue 
actuator can be turned in the opposite direction to recapture the bioprosthesis if the radiopaque 
capsule marker band has not yet reached the distal end of the spindle. The blue actuator also features a 
trigger, which can be engaged to make macro adjustments to the capsule position. A blue hand rest 
connects to the blue actuator. The end of the handle features a tip-retrieval mechanism, which can be 
used to withdraw the catheter tip to meet the capsule after the device has been fully deployed. 
The catheter packaging contains an integrated loading bath and a removable tray with 3 rinsing bowls 
for loading and rinsing the bioprosthesis. The integrated loading bath features a mirror, which aids in 
placement of the bioprosthesis frame paddles during loading. In addition, the device packaging is 
swiveled and secured to facilitate the bioprosthesis loading procedure. 
7.2.3. 
EnVeo PRO Loading System 
The loading system facilitates manual loading of the TAV into the deployment sheath capsule of the 
delivery catheter system by gradually reducing the diameter of the bioprosthesis radially to an optimal 
diameter (Figure 2B). The manual loading is performed during the procedure prior to implantation. The 
loading procedure is performed while immersing the loading system, the TAV, and the distal end of the 
delivery catheter system in cold sterile saline. 
 

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Figure 2. Medtronic CoreValve™ Evolut™ PRO System Components 
(A) Evolut PRO TAV (B) EnVeo PRO loading system (LS); (C) EnVeo PRO delivery catheter system (DCS) 
7.2.4. 
Manufacturer 
Medtronic CoreValve LLC 
 
 
 
7.2.5. 
Packaging 
The Medtronic CoreValve™ Evolut™ PRO system consists of the transcatheter aortic valve (TAV), EnVeo 
PRO delivery catheter system (DCS) and the EnVeo PRO loading systems (LS). Each of these components 
is packaged separately and its packaging evaluated individually. The finished TAV, DCS, and LS 
components were subjected to packaging validation studies to demonstrate packaging integrity and to 
confirm preservation of product sterility after sterilization, handling, distribution, and storage. 
The Instructions for Use (IFU) for the Medtronic Evolut™ PRO system used in this study will be provided 
as a separate document. Product labeling (Chinese) has been developed according to local 
requirements. All study devices will be labeled as per China regulations. Investigational devices will be 
labeled “Clinical trial use only” in accordance with NMPA China GCP 2022.23   

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7.2.6. 
Equipment 
Medtronic will control the supply of investigational devices and study materials (e.g., Investigator Site 
File, eCRF access).  First investigational device shipment at each site will occur after the Principal 
Investigator (PI) and key site personnel who handle storage of the device complete all device training 
and documented on the Delegated Task List. Medtronic will not provide any study-specific equipment to 
the sites. 
Study sites should follow their institutional procedures for maintenance of echocardiography and 
laboratory equipment used for assessing the study variables. 
7.3. Study trial 
The objective of this study is to evaluate the safety and efficacy of the Medtronic CoreValve™ Evolut™ 
PRO System when used by Chinese implanting centers in patients with severe symptomatic aortic 
stenosis (AS) who are at high risk for Surgical Aortic Valve Replacement (SAVR). 
The study population will include males and females with severe symptomatic aortic stenosis who are 
considered at high risk for SAVR.24  
8. Indications, contraindications and precautions of the 
investigational product 
The Medtronic Evolut PRO system is intended for relief of aortic stenosis in patients with symptomatic 
heart disease due to severe native calcific aortic stenosis who are judged by a heart team, to be at high 
risk for open heart surgery in the evaluation of the Evolut PRO China Clinical Study. The TAV treats aortic 
stenosis by displacing and functionally replacing the dysfunctional native valve with a bioprosthetic 
valve delivered on a catheter while the heart is still beating, thus avoiding the risks of cardiopulmonary 
bypass.25,26,27,28 Its intended performance is to relieve aortic valve stenosis without inducing significant 
regurgitation, thereby restoring effective aortic valve function.   
Refer to the Investigator’s brochure (IB) and Instructions for Use (IFU) document for intended use, 
indications and contraindications. See IFU also for mechanism of action, manufacturing information, 
model numbers, device identification, storage and handling requirements, summary of training and 
experience, description of medical procedures, and list of potential risks and warnings. 
9. Overall design  
9.1. Study design 
This is a prospective, observational, single arm, interventional, multicenter, premarket study.  The study 
objective will be assessed by evaluating the primary and secondary endpoints at 30 days. 

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9.1.1. 
Study objectives and/or Endpoints 
9.1.1.1. 
Study Objective(s) 
The objective of this clinical study is to evaluate the safety and efficacy of the Medtronic CoreValve™ 
Evolut™ PRO System when used by Chinese implanting centers in patients with severe symptomatic 
aortic stenosis (AS) who are at high risk for Surgical Aortic Valve Replacement (SAVR). 
9.1.1.2. 
 Primary Endpoints 
The following primary endpoints will be used to evaluate the study objective:  
Safety 
• 
All-cause mortality at 30 days 
Efficacy 
• 
The percentage of evaluable echocardiograms with moderate or severe aortic regurgitation at 30 
days by transthoracic echocardiography (TTE).  
9.1.1.3. 
Secondary Endpoints 
The following secondary endpoints will be used to evaluate the study objective:  
Safety 
1) The VARC II1 Combined Safety Endpoint at 30 days, which includes the following components: 
• 
All-cause mortality 
• 
All stroke (disabling and non-disabling) 
• 
Life-threatening bleeding 
• 
Acute kidney injury: stage 2 or 3 (including renal replacement therapy) 
• 
Coronary artery obstruction requiring intervention 
• 
Major vascular complication 
• 
Valve-related dysfunction requiring repeat procedure (BAV, TAVI, or SAVR)  
2) Event rates of the individual components of the VARC II composite safety endpoint at 30 days  
3) New permanent pacemaker at 30 days 
Efficacy 
1) Device success at 24 hours to seven days, defined as1:  

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• 
Absence of procedural mortality, AND  
• 
Correct positioning of a single prosthetic heart valve into the proper anatomical location, 
AND  
• 
Intended performance of the prosthetic heart valve, defined as the absence of patient-
prosthesis-mismatch and mean aortic valve gradient less than 20 mmHg (or peak velocity 
<3m/sec), AND absence of moderate or severe prosthetic valve regurgitation 
2) Valve performance parameters at 30 days by transthoracic echocardiography (TTE): 
• 
Mean aortic gradient 
• 
Effective orifice area 
• 
Degree of aortic regurgitation (transvalvular, paravalvular, total) 
9.1.1.4. 
Other Outcome Measures 
1) Event rates of the following TAVI-related complications: 
a. change to surgery 
b. need for cardiopulmonary mechanical assistance 
c. coronary occlusion or obstruction 
d. annular rupture or dissection 
e. ventricular perforation 
f. mitral valve damage  
g. prosthetic valve displacement, migration, or embolism  
h. acute kidney injury (up to 7 days post procedure) 
2) All-cause mortality at 6 months, one year, and annually through 5 years 
3) All stroke (disabling and non-disabling) at 6 months, one year, and annually through 5 years 
4) Myocardial infarction at 30 days, 6 months, one year, and annually through 5 years 
5) Life-threatening bleeding at 30 days, 6 months, one year, and annually through 5 years 
6) New AV-Conduction disturbances (LBBB and RBBB) at 30 days  
7) Prosthetic valve endocarditis at 30 days, 6 months, one year, and annually through 5 years 
8) Prosthetic valve thrombosis at 30 days, 6 months, one year, and annually through 5 years 
9) Valve-related dysfunction, defined as moderate or severe prosthetic valve stenosis, or moderate or 
severe prosthetic regurgitation (per VARC II) at one year and annually through 5 years  
10) Valve-related dysfunction requiring repeat procedure at 30 days, 6 months, one year, and annually 
through 5 years 
11) Valve hemodynamic performance metrics by Doppler echocardiography at one year and annually 
through 5 years 

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a. Mean aortic gradient 
b. Effective orifice area 
c. Degree of aortic regurgitation (transvalvular, paravalvular, total) 
12) New York Heart Association (NYHA) functional classification at 30 days, 6 months, one year and 
annually through 5 years 
13) Post-operative EQ-5D quality of life at 30 days and one year 
9.1.2. 
Selection of study method and rationale 
The basis for the selection of these endpoints includes the following considerations: 
1) They are clinically relevant and address the most important safety and efficacy aspects of the 
Evolut PRO and associated implant procedure 
2) They are objectively defined and measurable in all subjects 
3) They are consistent with current recommendations for endpoints in TAVR clinical studies.1 
4) They follow the NMPA “Guidelines for Clinical Trials of Trans-catheter Aortic Valve Implantation” 
(2019-03-01)29 
Collectively, the 30-day endpoints will provide a valid assessment to determine if the established safety 
and efficacy of the Evolut PRO system can be replicated by Chinese implanting centers in Chinese 
patients with severe symptomatic aortic stenosis at high risk for SAVR. 
9.1.3. 
Measures for reducing and avoiding deviation 
The study methods include the following measures to minimize potential sources of bias: 
1) An Eligibility Review Committee (ERC) will confirm subject eligibility and anatomical suitability. 
2) An independent Clinical Events Committee (CEC) will review and adjudicate, at minimum, all 
deaths and endpoint related adverse events. Safety endpoint results will be based on CEC 
adjudications. 
3) All sites will follow a standardized protocol for acquisition of echocardiographic endpoint data. 
4) An independent Echo Core Lab will evaluate all echocardiograms. Echocardiographic study 
endpoint results will be based on core lab assessments. 
5) Study sites should follow their institutional procedures for maintenance of echocardiography 
and laboratory equipment used for assessing the study variables. 
9.1.4. 
Investigational medical device and controlled medical device/diagnosis-
therapeutic method (if any) 
The Evolut PRO Transcatheter Aortic Valve Replacement (TAVR) System is the investigational device that 
will be evaluated in this single-arm clinical study.  

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Note: Effective 24-DEC-2021, National Medical Products Administration (NMPA) approved the 
Medtronic CoreValve™ Evolut™ PRO System for the treatment of severe aortic stenosis for symptomatic 
patients in China who are at high or extreme risk for open heart surgery. Overseas clinical data were 
utilized to support product registration. The Evolut PRO System will be commercially available during the 
Evolut PRO China Clinical Study enrollment period. However, only Evolut PRO System components that 
are labeled investigational (i.e., “Clinical trial use only”) will be used in the study. Commercial Evolut PRO 
System components will not be used in the study. 
9.1.5. 
Selection of subjects (including selection of control group if necessary) 
Subjects who meet the eligibility criteria and sign the informed consent form will participate in this 
study. Subjects who do not meet all inclusion criteria or meet any one of the exclusion criteria will not 
be enrolled to participate in the clinical study.  
9.1.5.1. 
Inclusion criteria 
Prospective subjects must meet all of following inclusion criteria to be eligible for implantation: 
1. Severe aortic stenosis, defined as aortic valve area of <1.0 cm2 (or aortic valve area index of <0.6 
cm2/m2) by the continuity equation, OR mean gradient >40 mmHg OR maximal aortic valve 
velocity >4.0 m/sec by resting echocardiogram 
2. High risk for SAVR defined as STS-PROM score ≥ 8% AND ≤ 15%, OR documented Heart Team 
agreement of high risk for AVR due to frailty or comorbidities 
3. Symptoms of aortic stenosis AND NYHA Functional Class II or greater 
4. The subject and the treating physician agree that the subject will return for all required post 
procedure follow-up visits 
9.1.5.2. 
Exclusion criteria 
Exclusion Criteria 
If any of the following exclusion criteria are present, the prospective subject is not eligible for 
implantation: 
1. Any condition considered a contraindication for placement of a bioprosthetic valve (e.g., subject 
is indicated for mechanical prosthetic valve) 
2. Age is less than 65 years 
3. A known hypersensitivity or contraindication to any of the following which cannot be 
adequately pre-medicated: 
• 
aspirin or heparin (HIT/HITTS) and bivalirudin 
• 
ticlopidine and clopidogrel  
• 
nitinol (titanium or nickel) 
• 
contrast media 
4. Blood dyscrasias as defined: leukopenia (WBC <1000 mm3), thrombocytopenia (platelet count 
<50,000 cells/mm3), history of bleeding diathesis or coagulopathy, or hypercoagulable states 
5. Untreated clinically significant coronary artery disease requiring revascularization 

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6. Severe left ventricular dysfunction with left ventricular ejection fraction (LVEF) <20% by 
echocardiography, contrast ventriculography, or radionuclide ventriculography 
7. End stage renal disease requiring chronic dialysis or creatinine clearance <20 cc/min. 
8. Ongoing sepsis, including active endocarditis 
9. Any percutaneous coronary or peripheral interventional procedure with a bare metal or drug 
eluting stent performed within 30 days prior to study procedure 
10. Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis 
within 10 weeks of written informed consent signed 
11. Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical 
hemodynamic support 
12. Recent (within 6 months of Heart Team assessment) cerebrovascular accident (CVA) or transient 
ischemic attack (TIA) 
13. Gastrointestinal (GI) bleeding that would preclude anticoagulation 
14. Subject refuses a blood transfusion 
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. Estimated life expectancy of less than 12 months due to associated non-cardiac co-morbid 
conditions 
17. Other medical, social, or psychological conditions that in the opinion of the investigator 
precludes the subject from appropriate consent or adherence to the protocol required follow-up 
exams 
18. Currently participating in an investigational drug or another device study (excluding registries) 
19. Evidence of an acute myocardial infarction ≤30 days before the study procedure 
20. Need for emergency surgery for any reason 
21. Liver failure (Child-Pugh class C) 
22. Patients requiring TAV implantation via carotid aortic access 
23. Currently undergoing radiation therapy 
Anatomical exclusion criteria: 
24. Pre-existing prosthetic heart valve in any position 
25. Mixed aortic valve disease (aortic stenosis with severe aortic regurgitation with predominant 
aortic regurgitation > 3+) 
26. Severe mitral regurgitation 
27. Severe tricuspid regurgitation 
28. Moderate or severe mitral stenosis 
29. Hypertrophic obstructive cardiomyopathy 
30. Echocardiographic or Multi-Detector Computed Tomography (MDCT) evidence of intracardiac 
mass, thrombus, or vegetation 
31. Non-calcified aortic valve 
32. Unicuspid valve verified by echocardiography 
33. Bicuspid aortic valve with no raphe or 2 raphes (Sievers classification type 0 or type 2) 
34. Sinus of Valsalva diameter unsuitable for placement of the self-expanding bioprosthesis 
35. Aortic annulus diameter of < 18 or > 26 mm. 

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36. Significant ascending aortopathy requiring surgical repair 
37. Ascending aorta diameter > 4.5 cm 
38. For transfemoral access vessel diameter < 5.5 mm or for transaxillary (subclavian) access < 6.0 
mm in patients with a patent left internal mammary artery (LIMA) 
9.1.5.3. 
Criteria and procedures for trial/treatment termination 
The subject will stop the implantation if there is an unexpected circumstance is encountered during the 
operation.  
9.1.5.4. 
Time of enrollment 
If the patient agrees to participate, written informed consent will be obtained. The date of the ERC 
confirms the subject is eligible will be considered the point of enrollment. 
9.1.5.5. 
Estimated duration of clinical trial and the reasons for determination 
Subjects will be consented for follow-up through 5 years. The enrollment phase of the study is estimated 
to be between 12 to 18 months; therefore, the estimated total duration of the study (first subject 
enrolled to last subject completing his/her last follow-up visit) is estimated to be 6.5-7 years, excluding 
the time required for preparing the study start-up, final report and study closure. 
9.1.5.6. 
Estimated participation duration of each subject 
Each implanted subject whether in the roll-in or primary study population will be followed up to 5 years 
post-procedure. Subjects who are taken to the procedure room for implantation but do not receive an 
Evolut PRO for any reason will be exited from the study within 30-days post the date of implant 
procedure unless a study system and/or implant procedure related Adverse Event (AE) is identified.  If a 
study system and/or implant procedure related AE is identified, the subject will be followed until the 
event is resolved or no further actions need to be taken. 
In the rare event the Evolut PRO TAV is explanted from the subject, their participation in the study ends 
following discharge from the explant hospitalization or 30 days post-explant (whichever comes later) to 
assess safety and then terminated from the study.  
9.1.5.7. 
Number of subjects required for clinical trial 
Estimating 65 subjects with a maximum of up to 70 subjects in China with an attempted implant, 
comprised of the following: 
• 
1) Primary study population: 50 subjects with an attempted implant using the Evolut PRO system 
2) Roll-in population:  The first two attempted subjects at each site will be considered “roll-in” 
subjects.  The maximum number of roll-in subjects among all sites will be 20 subjects. The roll-in 
population will be followed per the same protocol as the primary study population; however, results 
from the roll-in population will be analyzed separately from the primary study population. 

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9.1.6. 
Efficacy evaluation method 
The primary and secondary efficacy endpoints will be evaluated by quantitative assessment of 
transthoracic echocardiograms (TTE) by an independent Echo Core Laboratory and adjudication of the 
device success composite endpoint per the Valve Academic Research Consortium-2 (VARC II) definition1. 
9.1.6.1. 
Description of the efficacy parameters 
The efficacy parameters of aortic regurgitation and hemodynamic performance will be evaluated post-
transcatheter aortic valve implantation (TAVI) and at follow-up to assess valve durability and 
dysfunction. The composite endpoint of device success evaluates procedural mortality, positioning of 
the prosthetic valve in the proper anatomical location and performance of the prosthetic valve.  
9.1.6.2. 
Selection of method and time for evaluation, recording and analysis of the 
efficacy parameters 
Efficacy will be evaluated by the status of primary endpoint and secondary endpoints related with 
efficacy.  The efficacy endpoints were selected per the Valve Academic Research Consortium-2 (VARC II) 
recommendations1.  The primary efficacy endpoint is the percentage of evaluable echocardiograms with 
moderate or severe aortic regurgitation at 30 days.  Secondary efficacy endpoints are device success 
evaluated prior to discharge (at 24 hours to 7 days post-procedure) and hemodynamic performance at 
30 days. Statistical analysis of the efficacy parameters will be performed when the Implanted set (i.e., 
subjects who are implanted with the Evolut PRO, defined as the Evolut PRO is placed in the aortic 
annulus and completely released from the delivery catheter system) complete their 30-day follow-up 
evaluation.  Table 3 outlines the timing of the evaluations to assess the efficacy parameters.  
9.1.7. 
Safety evaluation method 
Adverse events (AEs) and serious adverse events (SAEs) and their outcomes including death will be 
reported throughout the study. Sites should capture or make every effort to collect source material for 
the safety-related endpoints and obtaining documentation of the cause of death, if available.  A Clinical 
Events Committee (CEC) will provide independent medical review and adjudication of adverse event 
data used in the safety endpoint assessment of the investigational device. The CEC will review source 
documentation to assess the clinical context from the implantation procedure leading up to the time of 
the event. 
9.1.7.1. 
Description of the safety parameters 
All-cause mortality adjudicated by the CEC will be categorized as cardiovascular and non-cardiovascular 
per the VARC II definition. 
9.1.7.2. 
Selection of methods and time for the evaluation, recording and analysis 
of the safety parameters 
Safety will be evaluated by the safety-related endpoints and reported adverse event (AE) and serious 
adverse event (SAE) data. The primary safety endpoint of all-cause mortality (cardiovascular and non-

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cardiovascular) will be evaluated at 30 days post-implantation per the VARC II definition1. Statistical 
analysis will be performed when the primary study population (n= 50 subjects with attempted implant, 
defined as all subjects who are brought into the procedure room and any of the following have 
occurred: anesthesia administered, vascular line placed, transesophageal echocardiology (TEE) placed, 
or any monitoring line placed) complete their 30-day follow-up evaluation.  Table 3 outlines the timing 
of the evaluations to assess the safety parameters. 
9.2. Trial procedures 
9.2.1. 
Study Site Investigative Team Members 
Investigative sites will meet the following criteria: 
1) Must be a medical institution qualified or filed in the NMPA clinical trial qualification 
certification system for conducting clinical studies by the regulatory department of NMPA and 
the Administrative Department of Health under the State Council. 
2) The site Principal Investigator will have experience as first or second operator for a minimum of 
five TAV implantations and/or have successfully completed Medtronic Transcatheter Aortic 
Valve Replacement (TAVR) operator training program. 
3) The site will have the presence or capacity of establishing an investigative team consisting of the 
following key personnel and their role/responsibilities provided in Table 2. 
 
 

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Table 2. Summary of Site Key Study Personnel 
Key Personnel 
Role/Responsibilities 
Interventional 
Cardiologist 
Each site will have at least one interventional cardiologist and one 
cardiothoracic surgeon with expertise in aortic valve replacement.  
The site Principal Investigation (PI) may be an interventional cardiologist or 
a cardiothoracic surgeon. The PI will undertake all the responsibilities of the 
investigator as required per NMPA regulations, and clinical trial agreement. 
In this study, the coordinating investigator of the leading site will 
coordinate the study with the Sponsor accordingly to the requirements in 
NMPA GCP23.  
Cardiothoracic surgeon 
Echocardiographer 
Each site will have a designated cardiologist whose primary responsibilities 
are to assure the required echocardiograms are performed in compliance 
with the CIP, and for reviewing and approving the site echocardiography 
eCRFs, if authorized by the PI. The designated echocardiographer may also 
serve as a member of the local Heart Team. 
Clinical Research 
Coordinator 
Each site will have a designated study coordinator whose responsibilities 
include coordination of study activities, follow-up evaluations, and 
maintaining the records defined in the CIP. 
Heart Team 
Each site will utilize a local Heart Team to make determinations regarding 
eligibility of the prospective subject for the study. In addition, the local 
Heart Team will confirm each enrolled subject meets the high-risk criteria 
for SAVR.  
At a minimum, the local Heart Team should include the following members: 
• 
A cardiothoracic surgeon 
• 
An interventional cardiologist 
The PI may serve as a member of the Heart Team. 
 
 
 

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9.2.2. 
Trial flow chart 
An overview of the study flow is shown in Figure 3:  
 
Figure 3. Study flow chart 
9.2.3. 
Subject Screening and Enrollment 
The process of patient screening and subject enrollment is as follows: 
1. Patients identified by the study site to have symptomatic aortic stenosis will be pre-screened by the 
investigative team for the criteria described in Section 9.1.5, Selection of Subjects, using available 
medical records, including relevant imaging studies that may have been previously performed for 
diagnostic purposes. 
2. If, based on the review of available information, the patient is deemed to be a potential candidate 
for the study, the investigational status of the Evolut PRO system and all aspects of the study will be 
explained to the patient. The patient will then be invited to participate in the study. 
3. If the patient agrees to participate, written informed consent will be obtained prior to undergoing 
any study-specific tests/procedures. The date of the signed informed consent will be considered the 
point of screening. The informed consent process should be documented in the patient’s medical 
record, and the subject shall be provided with a copy of the signed informed consent document. 
4. If the subject does not have a transthoracic echocardiography (TTE) available within 12 weeks of the 
submission to the Eligibility Review Committee (ERC), the subject will undergo a TTE.  If all 
echocardiographic criteria are met, the subject is eligible for further screening. 
5. Subjects that meet the echocardiographic criteria will undergo: 1) MDCT of their peripheral 
vasculature and aortic annulus to assess anatomic suitability for Evolut PRO implantationii, and 2) 
Heart Team assessment to determine their operative risk profile for SAVR. 
 
ii Anatomical suitability will be also be assessed by Medtronic Imaging Services Lab. Information on MDCT procedures and sizing 
recommendations is provided in Appendix III. 

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6. If the local Heart Team considers the subject to be suitable for implantation and at high risk for 
SAVR, the subjects’ clinical information will be submitted to the ERC. The following information 
should be submitted to the ERC: 
• 
Clinical assessments including STS-PROM, medical history and co-morbidities 
• 
TTE data on degree of aortic stenosis 
• 
MDCT data on anatomical suitabilityii 
7. The ERC will review clinical information to confirm the eligibility of the subject for implantation.  If 
the ERC confirms the subject is eligible, the date of the ERC confirms the subject eligibility will be 
considered the point of enrollment, and implantation should be performed within 90 days of ERC 
approval. 
8. Sites will maintain a log of patients consented, attempted, and implanted, as well as the Subject ID 
numbers assigned to each patient. Subjects who are consented but do not go forward to attempted 
implantation will be exited from the study. 
 
Figure 4 is a flow chart of subject screening and eligibility confirmation process leading up to the study 
implant procedure.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Point of enrollment 
Note 
1.
TTE or MDCT performed for diagnostic purposes prior to consent may be used, 
provided they are within window and contain the necessary data. 
Site pre-screens patient for eligibility 
Is patient a 
potential subject? 
Obtain Informed Consent 
Does subject meet 
criteria? 
Local Heart Team Assessment 
Does  Local Heart 
Team agree subject is 
eligible? 
Eligibility Review Committee (ERC) 
Assessment 
Exit from study 
Exit from study 
No 
No 
No 
Yes 
Yes 
Yes 
Point of screening 
Perform TT echo and MDCT
1 
Does ERC agree 
subject is eligible? 
Exit from study 
No 
Yes 
Implant 

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Figure 4. Flow chart of the study entry process 
9.2.3.1. 
Heart Team Risk Assessment 
Each screened subject will be evaluated by the local Heart Team to confirm they are considered to be 
high risk for SAVR according to the following definition: 
• 
STS-PROM ≥ 8% AND ≤ 15%, OR documented Heart Team agreement of high risk for AVR due to 
frailty or comorbidities 
Categorization of high risk will be based on the subject’s STS-PROM as well as additional risk factors not 
captured by STS-PROM, including: 
• 
porcelain aorta or severely atherosclerotic aorta 
• 
frailty  
• 
severe liver disease/cirrhosis  
• 
hostile chest 
• 
Internal mammary artery (IMA) or other critical conduit(s) crossing midline and/or adherent to 
posterior table of sternum 
• 
severe pulmonary hypertension 
• 
severe right ventricular dysfunction 
9.2.4. 
Required Evaluations 
Follow-up evaluations should be performed at the study site. The protocol required evaluations for each 
study interval are listed as follows and summarized in Table 3. 
Baseline/Pre-implant Required prior to Eligibility Review Committee (ERC) submission (within 12 
weeks prior to review by the ERC; except for MDCT)iii 
• 
Clinical assessment and history (e.g., clinical history, STS-PROM, co-morbidities, NYHA, symptoms, 
etc.)iv 
• 
Transthoracic echocardiogram (TTE) 
• 
Cardiac Multi-detector Computed Tomography (MDCT; peripheral vasculature and aortic annulus) 
• 
Heart Team assessment 
• 
Adverse Events  
Baseline/Pre-implant (performed upon ERC approval to Implant procedure) 
• 
12-lead ECG 
• 
Modified Rankin score (mRS) 
• 
EQ-5D Quality of Life survey 
• 
Adverse Events  
 Implant Procedure 
 
iii Pre-implant MDCT must be performed within 365 days of planned implant date 
iv Definitions of STS and other co-morbidities are provided in Appendix III 

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• 
Post deployment left ventricular and aortic pressures (hemodynamics) and aortography (final result) 
• 
Adverse Events  
• 
Device Deficiencies 
24 hours to 7 days Post Procedure (prior to Discharge) 
• 
TTE (for device success) 
• 
Adverse Events  
• 
Device Deficiencies 
Discharge (date of discharge or 7 days post procedure, whichever comes first) 
• 
Clinical assessment (NYHA not assessed at discharge) 
• 
Adverse Events  
• 
Device Deficiencies 
30 days (between 30 to 45 days post procedure) 
• 
Clinical assessment 
• 
TTE 
• 
12-lead ECG 
• 
EQ-5D Quality of Life survey 
• 
Adverse Events  
• 
Device Deficiencies 
6 months (between 183 to 210 days post procedure) 
• 
Clinical assessment 
• 
Adverse Events  
• 
Device Deficiencies 
One Year (between 365 and 395 days post procedure) 
• 
Clinical assessment 
• 
TTE 
• 
EQ-5D Quality of Life survey 
• 
Adverse Events 
• 
Device Deficiencies 
Annual through 5 years (between implant anniversary date and 30 days after) 
• 
Clinical assessment 
• 
TTE 
• 
Adverse Events  
• 
Device Deficiencies 
Other Evaluations 
• 
Modified Rankin score assessment should be conducted at 1 and 3 months following the date of a 
stroke event.1 

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Table 3. Summary of visit schedule and required evaluations 
Event 
Screening 
Index Hospitalization 
Follow-up Assessments 
Baseline 
(Local 
screening 
12 weeks 
prior to 
ERC) 
Baseline 
(ERC 
approval 
to 
Implant) 
Implant 
24 
Hours 
to 7 
Days 
Discharge 
30  
Days 
6  
Months 
1  
Year 
2-5 
Years  
Annually 
Clinic 
Visit 
Subject 
Contact1 
Clinic 
Visit 
Clinic 
Visit 
Clinical 
assessment 
X 
 
 
 
X2 
X 
X 
X 
X 
Adverse Event 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Device 
Deficiencies 
 
 
X 
X 
X 
X 
X 
X 
X 
MDCT 
X4 
 
 
 
 
 
 
 
 
TTE 
X 
 
 
X5 
 
X 
 
X 
X 
Heart Team 
Assessment 
X 
 
 
 
 
 
 
 
 
12-lead ECG 
 
X 
 
 
 
X 
 
 
 
Modified 
Rankin score6 
 
X 
 
 
 
 
 
 
 
Aortography 
 
 
X 
 
 
 
 
 
 
EQ-5D 
 
X 
 
 
 
X 
 
X 
 
1 Subject contact includes phone call, email or clinic visit 
2 NYHA assessment is not required at discharge  
3 Events are collected after the time of written informed consent signed 
4 Pre-implant MDCT must be within 365 days of planned implant date 
5 TTE for device success should be performed within 24 hours to 7 days post procedure 
6 Modified Rankin score assessment should be conducted at 1 and 3 months following the date of a stroke event 
 
 
Visit Windows 
Baseline 
Within 12 weeks prior to Eligibility Review Committee review 
Discharge 
Discharge from index procedure or 7 days post implant, whichever comes first 
30 Days 
Between 30 and 45 days post implant 
6 Months 
Between 183 and 210 days post implant 
1 Year 
Between 365 and 395 days post implant 
2-5 Years 
Between implant anniversary date and 30 days after 
 
 
 
 

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9.2.5. 
Recording Data 
Subject Disposition 
Sites will maintain a log of subjects consented, attempted, and implanted, as well as the Subject ID 
numbers assigned to each patient. Subjects who are consented but are not taken to the procedure room 
for implantation will be exited from the study and will not be followed beyond the date of study exit. 
Subjects who are taken to the procedure room for implantation but do not receive an Evolut PRO for 
any reason will be exited from the study within 30-days post the date of implant procedure unless a 
study system and/or implant procedure related Adverse Event (AE) is identified.  For subjects that have 
their Evolut PRO TAV explanted, their participation in the study ends following discharge from the 
explant hospitalization or 30 days post-explant (whichever comes later). 
Implant Procedure 
The implantation procedure is performed according to the standard procedures of the implanting 
physicians. Procedural aspects specific to the Evolut PRO system will be performed according to the 
Instructions for Use (IFU).  Valve size selection should be based on the anatomical dimension criteria 
described in Appendix III, Section 4.0. 
Data to be acquired during the implantation procedure include the following: 
• 
Name of the primary operator 
• 
Anesthesia type (general or local) 
• 
Delivery catheter access site and vessel diameter of access site 
• 
Pre-deployment BAV (yes/no) 
• 
Use of rapid or controlled pacing during BAV and deployment (yes/no) 
• 
Size of Evolut PRO TAV implanted 
• 
Post implant dilation (yes/no) 
• 
Post implant pressures at final result (LV systolic and end-diastolic, aortic systolic and 
diastolic, LV aortic peak-to-peak or mean gradient) 
• 
Implantation of Evolut PRO TAV within the desired location (yes/no) 
• 
Post implant severity of prosthetic regurgitation by angiography (none, 1+, 2+, 3+, 4+) by 
Sellers criteria30 
• 
Post implant severity of prosthetic paravalvular regurgitation by TEE, if performed 
• 
Post implant severity of prosthetic transvalvular regurgitation by TEE, if performed 
• 
More than one TAV implanted (yes/no) 
• 
Patency of coronary arteries post implant (yes/no) 
• 
Estimated contrast volume used 
• 
Total procedural time(minutes): time in procedure room to exit from procedure room  
• 
Occurrence of adverse events 
• 
If Evolut PRO implantation was not attempted, reason why 
Echocardiography 

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Transthoracic echocardiography (TTE) is required at the following intervals: pre-implant, 24 hours to 7 
days (for device success), 30 days, 1 year, and annually through 5 years. Exams will be sent to the Echo 
Core Lab for central assessment. Further details of the echocardiography methods are provided in 
APPENDIX II: ECHOCARDIOGRAPHY PROCEDURES. 
Sites will obtain the necessary views and measurements to document the following variables at each 
protocol-required exam: 
• 
Heightv and weight  
• 
Left ventricular outflow tract (LVOT) diameter in mid systole 
• 
Max aortic/prosthetic valve velocity (V2) by CW Doppler 
• 
Aortic valve velocity time integral (VTI) by CW Doppler 
• 
Mean gradient across aortic valve (MGV2) by CW Doppler 
• 
LVOT VTI by PW Doppler 
• 
Grade of aortic/prosthetic transvalvular regurgitation  
• 
Grade of prosthetic paravalvular regurgitation (post-implant only) 
• 
Grade of prosthetic total (transvalvular plus paravalvular) regurgitation (post-implant only) 
• 
Grade of mitral regurgitation 
• 
Grade of tricuspid regurgitation 
• 
Max tricuspid regurgitant (TR) jet velocity (if TR is present) 
• 
Left ventricular internal dimension at end diastole 
• 
Left ventricular internal dimension at end systole 
• 
Interventricular septal thickness at end diastole 
• 
Left ventricular posterior wall thickness at end diastole 
• 
Left atrial diameter (anterior-posterior linear dimension) at systole 
• 
Left ventricular ejection fraction 
In addition, the following variables will be derived by the central database from the appropriate 
measurements reported by the site: 
• 
Body surface area (Dubois and Dubois)31 
• 
Body mass index 
• 
Peak aortic pressure gradient 
• 
Aortic valve area (AVA)/effective orifice area (EOA) by continuity equation 
• 
Aortic valve area index (AVAI)/effective orifice area index (EOAI) 
• 
Doppler Velocity Index (DVI) 
Derived variables will be displayed on the eCRF upon entry of the appropriate raw measurements. The 
pre-implant qualifying AVA or AVAI must be based on the site reported variables for LVOT diameter, 
LVOT VTI, aortic valve VTI, height, and weight. 
Clinical Assessment 
 
v Height will be collected at the baseline (pre-implant) exam only.  Height for the post-implant exams will be derived from the 
baseline height. 

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Clinical assessment will be performed at the following intervals: pre-implant, discharge, 30 days, 6 
months, 1 year, and annually up to 5 years. 
The following variables will be documented at each protocol-required assessment: 
• 
Follow-up status 
• 
NYHA functional classification (except hospital discharge) 
• 
EQ-5D (at baseline, 30 days and one year only) 
• 
Documentation of adverse events and device deficiencies 
Missed Follow-up Visits 
Every effort should be made to ensure subjects return to the clinic for all protocol required follow-ups 
except for the 6-month subject contact (may be conducted by phone call, email or clinic visit). If the 
subject is unable to return for an in-person clinic visit, the Investigator, or designee, should document in 
the patient record the reason the subject was unable to complete the visit and, if applicable, follow the 
requirements for deviation reporting as outlined in Section 17.1. 
The investigator should also make every effort to contact the subject or subject’s legal representative, 
within the visit window to collect the subject’s vital status as well as information related to potential 
adverse events, safety data, and hospitalizations. 
Unscheduled Follow-up Visits 
If a subject returns to the study site or is contacted via telephone between their scheduled follow-up 
visits for an event potentially related to a study endpoint, the visit or telephone call will be treated as an 
unscheduled follow-up, and the assessments completed at this visit will be conducted at the discretion 
of the investigator. 
9.2.6. 
Subject Withdrawal or Discontinuation 
All subjects will be encouraged to remain in the study through the last follow-up visit at 5 years. Subjects 
who discontinue participation prematurely will be included in the analysis of results (as appropriate) and 
will not be replaced in the enrollment of total study subjects. If a study subject is discontinued from the 
study before study completion (including subjects with explants), the reason for discontinuation should 
be documented in the subject file and a Study Exit eCRF must be completed.  
The study site will make every effort to have all subjects complete the follow up visit schedule.  
Subject Lost-To-Follow-Up (LTFU) should be avoided as much as possible and investigators are urged to 
do their utmost best to maintain subject follow-up compliance. Continuous attempts throughout the 
five-year follow-up period should be made to contact the subject, the subject’s family or referring 
physician before documenting a subject LTFU. It is highly recommended to document each attempt to 
contact the subject and the method used (e.g. telephone contacts, registered letters) in the subject’s 
records. 
A subject will not be considered lost to follow-up unless all efforts to obtain compliance are 
unsuccessful. At a minimum, the effort to obtain follow-up information must include 3 attempts to make 
contact via telephone and if contact via phone is not successful, a traceable letter from the investigator 

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should be sent to the subject’s last known address. Should both telephone and mail efforts to contact 
the subject be unsuccessful, the subject’s primary physician should be contacted. In case a subject 
cannot be reached, all contact efforts to obtain follow-up must be documented in both the study files 
and on the study eCRFs. 
If a subject officially withdraws from the study but is willing to allow either regular vital status 
determinations or a one-time vital status determination prior to exiting the study, these are to be 
conducted per the follow-up visit schedule or only at the last planned follow-up visit, respectively, and 
may be conducted via telephone. 
If a subject discontinues the study at any time, is withdrawn from the study early, or completes all 
protocol required follow-up they should continue to be followed by the implanting site according to 
their routine clinical practice for TAV patients. If, for any reason, this is not possible for a particular 
subject, or if a subject needs to change his/her follow-up site at any time point after conclusion of the 
study, investigators should refer the subject to a local site with appropriate training and experience in 
managing patients with implanted transcatheter aortic valves.  
In addition, there is no post-study access of the investigational device for participants as initial 
treatment and the need for additional devices is not anticipated. 
9.2.7. 
Norms for using device 
9.2.7.1. 
Product and Study Training Requirements 
Prior to investigational site activation or subsequent involvement in study activities, Medtronic will 
provide training to the investigative team on the study methods, procedures, and requirements. 
Training may be conducted via site initiation visits, investigator meetings, and/or other media sessions. 
Medtronic will maintain documentation of these training sessions. For new study team members that 
join the study after site activation, the Principal Investigator may provide training on the study with 
permission from Medtronic. Additionally, Medtronic representative(s) may be present at each site’s 
implant procedures as part of the ongoing training process. 
Prior to each site’s first use, Medtronic will provide training to implanting physicians on the use of the 
investigational device following a similar training procedure applied to investigational studies conducted 
worldwide.  
9.2.7.2. 
Product Receipt and Tracking 
In this study, the Evolut PRO system including the Transcatheter Aortic Valve (TAV), Delivery Catheter 
System (DCS) and Loading System (LS) are considered investigational devices in China.  Sites are 
responsible for maintaining records for product delivery, receipt and tracking and product disposition to 
allow for traceability during and after the clinical investigation.  Sites are required to maintain 
investigational device records that contain the following information: 
• 
Investigational device name 
• 
Serial number / Lot number  

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• 
Quantity of devices received  
• 
Date of receipt of device 
• 
Name of person receiving the device 
• 
Name of person using the device 
• 
Date of implant or use 
• 
ID number of subjects receiving or using the device 
• 
Disposition (implanted, disposed of, or returned to Medtronic) 
9.2.7.3. 
Product Storage 
The Evolut PRO system should be labelled and stored in a secure location. The method of storage should 
prevent the use of these investigational devices for other applications than mentioned in this CIP.   
9.2.7.4. 
Product Accountability 
Device accountability records must be maintained at the study site. The quantity of devices received by 
the study site, those returned, and those devices used at the study site will be recorded in device 
accountability records. The Investigator or an authorized designee must explain in writing the reasons 
for any discrepancy noted in device accountability. When the study enrollment is complete, the 
Investigator shall return any unused devices, opened or unopened, to Medtronic. 
Medtronic and/or its designee will train the Investigator and appropriate site personnel on device-
tracking instructions and requirements, which will include the site’s record keeping responsibilities of 
receipt and disposition of all investigational devices shipped to and returned by the site.  
Note:  for additional information on shipment, receipt, and return of study devices refer to the device 
tracking instructions. 
9.2.7.5. 
Product Return 
Once enrollment for the study is identified by the sponsor as closed, the Investigator must return any 
unused devices to Medtronic and send a copy of the completed device inventory. The investigator’s 
copy of the device reconciliation records must document any unused devices that have been returned to 
Medtronic as well as all product usage including opened but non-implanted devices. 
For devices that are returned to Medtronic or disposed of, sites are required to document the following 
information: 
• 
The device serial numbers / Lot numbers  
• 
The quantity and reason for the device being returned to Medtronic or disposed of 
• 
Name of the person who returned or disposed of each device 
• 
Date of shipment back to Medtronic 

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9.2.7.6. 
Device Malfunction or Explant 
In the event of a device malfunction of the TAV device or its components prior to implant, or in the 
event a TAV is explanted after implant, the TAV and/or affected components should be disposed at 
study site according to hospital requirements.   
9.3. Monitoring plan 
Monitoring visits and/or remote reviews will be conducted at the start, during and at the closure of the 
clinical study in accordance with Medtronic SOPs and the Monitoring Plan.  Investigational sites will be 
monitored to ensure compliance with the study protocol (including the informed consent process), 
adherence to applicable regulations, accuracy of study data, and to ensure the safety and wellbeing of 
the subjects is preserved.  Prior to subject enrollment, an initiation visit will be completed with each site. 
Monitoring visits will also be used to verify that study data submitted on case report forms are complete 
and accurate with respect to the subject records and to verify device accountability. 
Site personnel will complete electronic case report forms (eCRFs) following each subject study schedule.  
Study data submitted will be reviewed against subject charts and other sources containing original 
records of subject data.   
Upon study completion, Site Closeout Visits will be conducted, as outlined in the Monitoring Plan. 
Monitoring will be provided by representatives of Medtronic, including but not limited to, Medtronic 
Core Clinical Solutions with oversight from the Medtronic clinical project manager and study team. 
Representatives of Medtronic (i.e. contractors and designees) may act as the study monitors or co-
monitors to the site.   
Prior to the first site activation a monitoring plan will be established outlining the activities, as well as 
study site training, the process for corrective and preventive actions, audit preparation and inspection 
support. Source data verification (SDV) will be performed and the extent of SDV will be described in the 
monitoring plan. 
The principal investigator(s), his/her delegate(s) and the study coordinator(s) are expected to be present 
and available during the monitoring visit to discuss monitoring outcomes. This accessibility is of 
particular importance for reviewing data in the eCRF. Direct access to subject medical files for source 
data verification will need to be granted and prepared prior to any monitoring visits. 
10. Statistical consideration  
10.1. Statistical design, method and analysis procedures 
This is a prospective, single arm, multi-center, interventional, pre-market study. The primary endpoints 
are all-cause mortality and the percentage of evaluable echocardiograms with moderate or severe 
prosthetic aortic valve regurgitation at 30 Days.  As this is not a powered hypothesis-driven study, the 
sample size was not determined by statistical methods.  The sample size is consistent with the 50 
subject minimum as outlined NMPA TAVI Clinical Trial Guideline29. 

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Subjects who are taken to the procedure room and attempt the implantation will comprise the study 
population evaluated for the study objectives and associated endpoints.  Data from subjects enrolled as 
roll-ins  will not be combined with the primary analysis cohort and will be analyzed separately. The 
analysis subsets for the study endpoints are shown in Figure 5. 
 
Figure 5. Analysis sets for the study endpoints 
There are 2 main analysis sets for the primary study population:  
1. Attempted implant set. Includes all subjects who are brought into the procedure room and any 
of the following have occurred: anesthesia administered, vascular line placed, TEE placed, or any 
monitoring line placed.  
2. Implanted set. Includes all subjects who are implanted with the Evolut PRO, defined as the 
Evolut PRO is placed in the aortic annulus and completely released from the delivery catheter 
system. 
Statistical analysis will be performed when the primary study population (n= 50 subjects with attempted 
implant, exclusive of “roll-in” patients) are followed for 30 days.  Results for the baseline characteristics 
and the primary and secondary endpoints from the 60-subject TAVR 2.0 US Clinical Study (Evolut PRO) 
will be provided for descriptive comparison.  In addition, results will be descriptively compared to 
available results for other commercially approved TAVR systems in China. 
Data will be analyzed and Clinical Study Reports (CSRs) will be prepared for the primary endpoint (at 30 
days) and for the final analysis.  The final analysis will be performed when all implanted subjects have 
completed their 5-year follow-up. Annual CSRs may also be prepared after the primary endpoint and 
prior to the final analysis CSRs, per the discretion of the Sponsor. 
Attempted implant set 
Implanted set 
Subjects consented 
Subjects who go to 
procedure room for 
Implantation 
Subjects who do not go to 
procedure room for 
Implantation 
Subjects 
implanted 
Subjects attempted, 
not implanted 
Roll-in Subjects 
attempted 
implant 

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10.1.1. 
Primary Endpoint Analyses 
The primary safety endpoint of all-cause Mortality at 30 Days will be analyzed for the Attempted implant 
set. The Kaplan-Meier rate and a 95% two-sided confidence interval will be calculated.  
The primary efficacy endpoint of aortic regurgitation at 30 Days will be analyzed for the Implanted set. 
The number and percentage of subjects with evaluable echocardiograms with moderate or severe total 
(paravalvular plus transvalvular) aortic regurgitation will be calculated. A 95% two-sided confidence 
interval for aortic regurgitation will be calculated. 
10.1.2. 
Secondary Endpoint Analyses 
The secondary safety endpoints of VARC II Combined and Individual Safety Components and new 
permanent pacemaker at 30 days will be analyzed for the Attempted implant set. The Kaplan-Meier 
rates and 95% two-sided confidence intervals will be calculated. 
The secondary efficacy endpoint of Device Success will be analyzed for the Attempted implant set. The 
number and percentage of subjects that meet device success criteria will be calculated. A 95% two-sided 
confidence interval for the device success rate will be calculated. 
The secondary efficacy endpoint of valve performance parameters at 30 Days will be analyzed for the 
Implanted set. Descriptive statistics for the following hemodynamic variables will be provided: 
• 
Mean aortic gradient 
• 
Effective orifice area 
• 
Degree of aortic valve regurgitation (transvalvular, paravalvular, total) 
For continuous variables the number of subjects, means, medians, standard deviations, and ranges will 
be presented. For categorical variables the number of subjects, total number of subjects, and 
percentages will be presented. 
10.2. Calculation of sample size 
As this is not a powered hypothesis-driven study, the sample size of 50 attempted subjects was not 
determined by statistical methods. Rather, it was based on adherence to the NMPA TAVI Clinical Trial 
Guideline29 and was confirmed during the NMPA consultation meetings and protocol synopsis submitted 
with no further objections/feedback (October 2018 through March 2019).    
10.2.1. 
Total sample size 
The total sample size of the primary study population is 50 attempted implants, exclusive of the roll-in 
population.  

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10.2.2. 
Case number for each disease in clinical trial and reasons for 
determination 
All 50 attempted implants that make up the primary study population will be categorized as high risk for 
surgical aortic valve replacement (SAVR).  The sample size is consistent with the 50 subject minimum as 
outlined NMPA TAVI Clinical Trial Guideline29. 
10.2.3. 
Minimum and maximum number of subjects for each clinical trial 
institution in multicenter clinical trial 
There is no minimum number of subjects required for each clinical institution. No site will implant more 
than 20 subjects, excluding the roll-in subjects, without prior authorization from Medtronic.  
10.3. Significance level and study power of clinical trial 
As this is not a powered hypothesis-driven study, formal hypothesis testing will not be performed. 
10.4. Estimated drop-out rate 
Since the study primary safety and efficacy endpoints are at 30 days, a minimal amount of missing data 
is anticipated for the primary endpoints. The estimated clinical attrition and lost to follow-up rate is less 
than 20% for the 5-year follow-up duration. 
10.5. Criteria for acceptability/unacceptability of clinical trial 
results 
Statistical analysis will be performed by the leading site with collaboration support and oversight from 
the Sponsor. Statistical analysis will be performed when the primary study population (n= 50 subjects 
with attempted implant, exclusive of “roll-in” patients) are followed for 30 days.  Results for the baseline 
characteristics and the primary and secondary endpoints from the 60-subject TAVR 2.0 US Clinical Study 
(Evolut PRO) will be provided for descriptive comparison. Criteria for acceptability/unacceptability is not 
applicable as this is not a powered hypothesis-driven study.  The leading site will be consulted to review 
the clinical trial results for acceptability/unacceptability.  
10.6. Criteria and reasons for trial termination based on statistics 
Interim analysis and corresponding early termination criteria are not planned for this trial. Hence, this 
section is not applicable. All statistical analysis will be performed after completing data collection, data 
review and data cleaning is confirmed. 

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10.7. Statistical methods for all data, and processing of missing, 
unused, wrong (including withdrawal and drop out) or 
abnormal data 
Every effort will be undertaken to minimize missing data. In time-to-event outcomes, drop-outs will be 
censored at the time of discontinuation, consistent with the Kaplan-Meier approach.   
Unless otherwise specified in each objective, no statistical techniques will be used to impute missing 
data for continuous or categorical outcomes. If a subject’s data are missing for any reason, that subject 
will not be included in that portion of the analysis. Erroneous (i.e., wrong including withdrawal and drop 
out) and abnormal data will be cleaned prior to performing the database snapshot for the statistical 
analyses.  The number of subjects included in each analysis will be reported so that the reader can 
assess the potential impact of missing data.   
10.8. Reporting of procedure deviations from the original 
statistical plan 
The statistical analysis plan (SAP) will be confirmed by the sponsor and the coordinating 
investigator/leading site and finalized before a database snapshot is performed for analysis. The SAP 
may be modified to consider actual scenarios observed during the study phase before final approval. In 
principle, major analysis methods or analysis sets will not be changed. All revisions will be recorded. 
10.9. Criteria for selection of the subjects for analysis set and 
reasons 
Statistical analysis sets should be clearly defined prior to the time when analysis is carried out. The two 
main analysis sets for this study are defined as follows: 
1. Attempted implant set. Includes all subjects who are brought into the procedure room and any 
of the following have occurred: anesthesia administered, vascular line placed, TEE placed, or any 
monitoring line placed.  
2. Implanted set. Includes all subjects who are implanted with the Evolut PRO, defined as the 
Evolut PRO is placed in the aortic annulus and completely released from the delivery catheter 
system. 
Statistical analysis will be performed when the primary study population (n= 50 subjects with attempted 
implant, exclusive of “roll-in” patients) are followed for 30 days.   
10.10. Exclusion of special information during assumption 
validation and reasons thereof (if applicable) 
There is no hypothesis testing in this study, hence it is not applicable to require excluded information for 
hypothesis testing. If there are special information observed in the study, it will be evaluated on a case 
by case basis and documented in the report. 

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11. Data management 
11.1. Data Collection 
11.1.1. 
Electronic Case Report Forms (eCRFs) 
The investigator must ensure accuracy, completeness and timeliness of the data reported in the eCRFs 
and in all other required reports. Data reported on the eCRFs which are derived from source documents 
must be consistent with the source documents and discrepancies need to be justified in a documented 
rationale, signed and dated by the (principal) investigator, and filed in the patient medical file. 
Only authorized persons can complete eCRFs. eCRFs shall be signed by investigational center staff as 
specified on the Delegation of Authority Log included in the Investigator Site Binder. The study 
Electronic Data Capture (EDC) system maintains an audit trail on entries, changes and corrections in 
eCRFs.  
A copy of the eCRFs to be used in this clinical study is available under a separate cover, upon request to 
the sponsor and in the Investigator Site Binder.  
Investigational center will be trained for use of the eCRF prior, or at latest during, investigational center 
initiation visit, on a training database. Access to final eCRFs for study conduct will be granted after 
training is performed. 
11.1.2. 
Subject Questionnaires 
Subject questionnaires will be collected on paper that will be kept at the investigational center. The 
investigator, or designated investigational center staff, will then enter the answers of the subject on the 
paper questionnaires into EDC system. It is important that the investigator or designated investigational 
center staff verifies questionnaires for completeness.  
11.1.3. 
Time Windows For Completion and Submission of eCRFs 
It is expected that eCRFs are completed in a timely manner with the exception of all AEs (see Section 
16.7), which need to be recorded within 24 hours in the eCRF after awareness of the investigator or 
investigational center staff to the event. After data entry, eCRFs should be submitted (i.e. saved) so that 
Monitors can proceed with data verification without delay.  
11.1.4. 
Data Review and Processing 
The leading investigational center will be accountable for data management and analysis about the data 
from each clinical research institution in a centralized manner according to local regulations and study 
requirements. Medtronic will oversee all data management functions and provide support if 
necessary.32  
Collected data will be reviewed for completeness, correctness and consistency, as per the Monitoring 
Plan and Data Management Plan. In case of issues, queries will be entered on the respective eCRF for 
the investigator or authorized designee to complete, correct or comment on the data.  

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12. Feasibility analysis  
12.1. Probability analysis of success 
The Medtronic manufacturing system is established, governed by quality system procedures and 
regularly audited by various auditing bodies from around the world. The quality of the investigational 
device is carefully examined and verified before delivery. The investigational device has been 
commercially available globally, including in the United States, Europe and other countries.  The Evolut 
PRO system has been studied in pre-market and post-market follow-up clinical studies.  The basic 
principles, structure composition, and materials either comply with the international and/or domestic 
standards or have been carefully examined and verified by Medtronic.  Additionally, Evolut PRO testing 
has been completed by an NMPA-certificated medical device testing organization.  
The study design of this study complies with related NMPA instructions and requirements of ethical 
review, and all potential subjects will be strictly selected according to indications of the investigational 
device. 
As this is not a powered hypothesis-driven study, the probability of success is not applicable. However, it 
is anticipated that the safety and efficacy profile will be similar to the overseas Evolut PRO data.  
12.2. Probability analysis of failure 
Although regulatory, ethical, scientific and medical requirements have been fully taken into 
consideration, the unanticipated risk in the clinical application of investigational device could lead to 
failure of this study. Potential risks could be reduced with well-trained study staff and strict protocol 
compliance. 
As this is not a powered hypothesis-driven study, the probability of failure is not applicable. However, 
we anticipate the safety and efficacy profile will be similar to the overseas Evolut PRO data.  
13. Risks and Benefits 
The results of risk analysis, balancing benefits against risks associated with both the device system itself 
and procedures involved in its use, are included in the Investigator’s Brochure (IB) and the Instructions 
for Use (IFU). Based on the risk assessments performed, the overall residual risk based on the potential 
Evolut PRO system design and use related risks have been determined to be acceptable and is exceeded 
by the benefits of TAVR to the patient.  
13.1. Potential Risks 
As with any TAVR procedure, there are risks associated with implantation of a TAV. However, the risks to 
a patient for participation in the Evolut PRO China study are not materially different than those a patient 
would incur if they underwent TAVR outside of the study. 

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TAVR has been associated with serious complications, including death. In addition, complications may 
occur at varying intervals necessitating re-intervention or surgical replacement of the TAV. Known 
complications that may result from TAVR include but are not limited to the following:  
• 
Death 
• 
Cardiac arrest 
• 
Coronary occlusion, obstruction, or vessel spasm (including acute coronary closure) 
• 
Urgent surgery (e.g., coronary artery bypass, heart valve replacement, valve explant) 
• 
Multi-organ failure 
• 
Heart failure or low cardiac output 
• 
Myocardial infarction  
• 
Cardiogenic shock 
• 
Respiratory insufficiency or respiratory failure 
• 
Cardiovascular injury (including rupture, perforation, or dissection of vessels, ventricles, 
myocardium, or valvular structures that may require intervention) 
• 
Perforation of the myocardium or a vessel 
• 
Stroke (ischemic or hemorrhagic) or other neurological deficits 
• 
Transient ischemic attack 
• 
Permanent disability 
• 
Urgent need for balloon valvuloplasty (note that BAV during implantation is expected) 
• 
Urgent need for Percutaneous Coronary Intervention (PCI) 
• 
Major or minor bleeding that may or may not require transfusion or intervention (including life-
threatening or disabling bleeding) 
• 
Cardiac tamponade 
• 
Ascending aorta trauma 
• 
Disturbances in the electrical system of the heart that may result in the permanent placement of a 
device (pacemaker) 
- 
Atrio-ventricular node block  
- 
Bundle branch block  
- 
Asystole  
• 
Cardiac arrhythmias  
• 
Thrombosis (including valve thrombosis) 
• 
Valve migration/embolization 
• 
Ancillary device migration/embolization (including components of the delivery catheter system) 
• 
Prosthetic valve dysfunction including but not limited to: 
- 
Fracture 
- 
Bending (out-of-round configuration) of the valve frame 
- 
Under-expansion of the valve frame 
- 
Calcification  
- 
Pannus 
- 
Wear, tear, prolapse or retraction in the valve leaflet 
- 
Poor valve coaptation 
- 
Suture breaks or disruption 
- 
Leak 

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- 
Mal-sizing (prosthesis-patient mismatch) 
- 
Malposition (either too high or too low) 
- 
Valve regurgitation (paravalvular or transvalvular) 
- 
Valve stenosis 
• 
Mitral valve regurgitation or injury 
• 
Hypotension or hypertension 
• 
Renal insufficiency or renal failure (including acute kidney injury) 
• 
Allergic reaction to antiplatelet agents, contrast medium, or anesthesia 
• 
Infection (including septicemia; bioprosthetic or native valve endocarditis)  
• 
Vascular access site or access related complications, including but not limited to: 
- Dissection 
- Perforation 
- Pain 
- Bleeding 
- Hematoma  
- Pseudoaneurysm 
- Irreversible nerve injury 
- Compartment syndrome 
- Arteriovenous fistula 
- Stenosis 
• 
Tissue erosion 
• 
Encephalopathy 
• 
Pulmonary edema 
• 
Pericardial effusion 
• 
Pleural effusion 
• 
Myocardial ischemia 
• 
Peripheral ischemia 
• 
Bowel ischemia 
• 
Heart murmur 
• 
Hemolysis 
• 
Cerebral infarction-asymptomatic 
• 
Non-emergent reoperation 
• 
Inflammation 
• 
Fever 
• 
Syncope 
• 
Dyspnea 
• 
Anemia 
• 
Angina 
• 
Abnormal lab values (including electrolyte imbalance) 
• 
Exposure to radiation through fluoroscopy and angiography 
• 
Delivery catheter malfunction resulting in need for additional re-crossing of the aortic valve and 
prolonged procedural time 

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13.2. Potential Benefits 
The Medtronic CoreValve™ Evolut™ PRO system has been approved in the United States (i.e., Country of 
Origin) for indication of use in patients with symptomatic severe aortic stenosis who are at high risk or 
greater for operative mortality with SAVR.  The primary potential benefit to subjects participating in the 
study is to restore function of their diseased (stenotic) native aortic valve. Other potential benefits 
include avoiding the risks of open-heart surgery and cardiopulmonary bypass and an earlier return to 
normal activities than after open heart surgery. 
13.3. Risk-Benefit Rationale 
The Evolut PRO system has been studied in pre-market and post-market clinical studies in the United 
States, Europe and other countries.  TAVR with the Evolut PRO system has been shown to be a safe and 
effective treatment for patients with severe aortic stenosis who are at high risk or greater for operative 
mortality with surgical aortic valve replacement (SAVR).  
Available pre-market and real-world clinical evidence on TAVR in tricuspid and bicuspid patients has 
demonstrated that implantation of the Evolut R and Evolut PRO transcatheter aortic valves can be 
accomplished by multiple operators with a high degree of technical success and with an acceptably low 
level of procedural complications. Results demonstrated comparable outcomes for bicuspid patients as 
compared to tricuspid patients who were deemed at increased risk for SAVR (intermediate and above).  
This study is designed to confirm the safety and efficacy of the Evolut PRO system in the Chinese patient 
population. Although there are risks to the study subjects for participation in the study, they are 
anticipated to be similar to the risks of undergoing TAVR outside of the study. The study endpoints are 
clinically relevant and consistent with the study objectives. The overall study design is confirmed with 
the NMPA TAVI Guideline29 was confirmed during the NMPA consultation meetings and protocol 
synopsis submitted with no further objections/feedback (October 2018 through March 2019).  
Therefore, the study as described is justified. 
 
 

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Measures to Mitigate Risks to Study Subjects 
The following measures will be implemented to minimize risks to the study subjects: 
• 
Implanting physicians will have experience with TAVR 
• 
Implanting physicians will undergo didactic and simulator training prior to the study start at each 
site 
• 
Patients will be rigorously followed over the course of the study 
Alternatives 
Presently, therapeutic alternatives for patients with the clinical indication targeted for the Evolut PRO 
system include the following: 
• 
Medical therapy 
• 
Balloon aortic valvuloplasty 
• 
Surgical aortic valve replacement 
• 
TAVI with another device approved in China 
14. Quality control of clinical trial 
Per NMPA GCP (China GCP 2022) 23, before site activation, Medtronic will reach a written agreement 
with clinical trial institutions and investigators on trial quality control. Medtronic will develop standard 
operating procedures related to quality control of clinical trials, such as the transportation, receiving, 
storage, distribution, disposal and return of investigational medical devices, which shall be followed by 
clinical trial institutions and investigators. These should also be covered in the written agreement.  
15. Ethical issues and informed consent of clinical trial 
15.1. Ethical considerations  
15.1.1. 
Statement of Compliance  
This study is a pre-market clinical trial to evaluate the safety and efficacy of the Medtronic CoreValve™ 
Evolut™ PRO System when used by China implanting centers in Chinese patients with severe 
symptomatic aortic stenosis (AS) who are at high risk for Surgical Aortic Valve Replacement (SAVR). The 
study will be conducted in accordance with the laws and regulations of China, including any future 
applicable laws and regulations in China.  
This protocol, any subsequent amendments to this protocol, the Informed Consent/Assent form, subject 
material and any form of subject recruitment information (e.g. advertisements) relating to this study will 
be approved by the responsible EC in accordance with NMPA China GCP 202223 and local regulatory 
requirements as applicable. The study will not start until EC approval has been granted, the sponsor has 
cleared the investigational center to begin the study, and the investigational center staff has been 
appropriately trained to conduct the study. Copies of all relevant correspondence between the 

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investigational center and the EC will be retained at investigational center with copies forwarded to the 
sponsor for their files.  
Regulatory Compliance 
To protect the rights and welfare of patients, this clinical study will be conducted in compliance with the 
latest version of the Declaration of Helsinki, the Clinical Trial Agreement and CIP, the laws and 
regulations of China including Good Clinical Practice for Medical Devices (China GCP 2022)23, 
Announcement of NMPA on Filing of Medical Device Clinical Trial (2015, No. 87) and also including 
applicable data protection laws. Investigational centers will also comply with any additional EC 
requirements applicable. 
The principles of the Declaration of Helsinki have been implemented through the patient informed 
consent process, EC approval, study training, clinical trial registration, preclinical testing, risk-benefit 
assessment and publication policy. The clinical trial filing will be completed prior to conduct of this study 
per the requirement of the Announcement of NMPA on Filing of the Medical Device Clinical Trial (2015, 
No. 87).  
Regulatory Submission 
Sponsor should be responsible for filing the study to Shanghai Municipal Food and Drug Administration 
after EC approval of the current version of the CIP and fully executed Clinical Trial Agreement. 
Sponsor’s Support  
The sponsor shall avoid improper influence on, or inducement to, the subject, monitor, any 
investigator(s) or other parties participating in or contributing to this study. 
Sponsor representatives may provide support as required for the study, including technical support at 
investigational center. Sponsor representatives may provide technical support as required for the study 
under supervision of the PI, including: 
1) Provide study training relevant and pertinent to the involvement of personnel conducting study 
activities and investigator responsibilities. 
2) Technical support will be provided during study period. 
3) Technical support will be under the supervision of a study investigator, but no data entry on the 
eCRF shall be performed by Medtronic personnel or their representatives at investigational 
centers. 
4) Technical support to conduct device interrogations.  
15.1.2. 
Investigator’s Responsibilities 
This study will be conducted at the investigational centers where all study-related activities will be 
performed and will be led by a PI. An investigator is an individual who actually conducts a clinical 
investigation (i.e., under whose immediate direction the test article is administered or dispensed to, or 
used involving, a subject) or, in the event of an investigation conducted by a team of individuals, is the 
responsible leader of that team. 

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The investigator’s responsibilities include but are not limited to: 
• 
Conduct of the investigation in accordance with the CIP, the regulations as outlined in NMPA 
that apply to this study and other applicable regulations, and any conditions of approval 
imposed by the reviewing EC 
• 
Conduct of investigation in accordance to regulations from NMPA to meet responsibilities with 
respect to protect human subjects and ensuring the integrity of the data from clinical 
investigations. The regulations are also intended to clarify NMPA’s expectations concerning the 
investigator’s responsibility:  
o to supervise a clinical study in which some study tasks are delegated to employees or 
colleagues of the investigator or other third parties, and  
o to protect the rights, safety, and welfare of study subjects. 
• 
Supervision of all testing of the device involving human subjects 
• 
Ensuring that the requirements for obtaining informed consent are met in accordance with 
NMPA 
• 
Allowing study devices to be used only with subjects under the investigator’s supervision and to 
supply study devices only to persons authorized to receive it 
• 
Ensuring that investigational center staff are adequately trained to perform their assigned duties 
• 
Maintenance of accurate, complete, and current records relating to the investigator’s part of an 
investigation, to include 
o all relevant correspondence with Medtronic and EC 
o records of receipt, use, or disposition of a device 
o records of each subject’s case history and exposure to the device 
o the CIP, with documents showing the dates of and reasons for each deviation from the 
CIP 
• 
Preparation and submission to Medtronic and, when required, the reviewing EC, the following 
complete, accurate, and timely reports: 
o all AEs (see Section 16.7) occurring during an investigation 
o progress reports on the investigation as required by the EC 
o protocol deviation that may affect the subjects’ rights and interests, safety, health or 
the scientific integrity of clinical trials, including deviation regarding requests and 
reports 
o any use of the device without obtaining informed consent 
o any further information requested by the EC about any aspect of the investigation 
• 
Meeting with the monitor to discuss study progress and findings 

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• 
Ensuring that investigational center resources are adequate to fulfill the obligations of the study 
• 
Ensuring completion of eCRF to include: entry and addressing discrepancies in a timely fashion 
and approving selected eCRFs. It is expected that data is entered into EDC. Failure to keep up 
with entry of study data may result in study payment delay.  
Only authorized study personnel, as listed on the Delegation of Authority Log, are permitted to consent 
subjects, receive, dispense, dispose of and return investigational products, conduct subject visits, insert 
devices and enter data on eCRFs. These tasks may be delegated by the investigator; however, the 
investigator is ultimately responsible to ensure investigational center staff are qualified and perform the 
tasks that have been delegated to them. In addition, the investigator is responsible for the conduct of 
investigational center in the execution of the clinical trial. 
The investigator’s signature on the Investigator Statement and Signature Page confirms that the 
investigator is familiar with the CIP in its entirety and agrees to conduct this study in accordance with 
the provisions of the CIP and all applicable regulations.  The investigator, prior to the initiation of any 
study related activity, will sign the Investigator Statement and Signature Page. If the sponsor discovers 
that an investigator is not complying with the Investigator Statement and Signature Page, CIP, or other 
regulatory requirements, the sponsor shall promptly secure compliance or discontinue that 
investigator’s participation in the study. 
15.2. Examination and approval of study protocol 
The study will be conducted in accordance with the requirements of local Ethics Committees.  The 
responsible Ethics Committee (EC) at each investigational site must approve the study protocol and 
consent.  Study activities will not commence prior to receipt of documentation of EC approval by the site 
and Medtronic.  The Investigator and study site staff must comply with the requirements of their EC. 
Prior to enrolling subjects, each investigational site’s EC will be required to approve all necessary study 
documents including the CIP, the Informed Consent Form (ICF) and any other written information to be 
provided to the subjects.  EC approval of the clinical study must be received in the form of a letter and 
provided to Medtronic before commencement of the study at an investigational site.  The approval 
letter must contain enough information to identify the version or date of the documents approved.  If 
this information is not contained in the approval letter, it must be retrievable from the corresponding 
submission letter. If the EC approval letter is not in English, the Medtronic clinical study team must 
ensure documented review of the letter in English, or a translation to English must be obtained. In 
addition, the approval letter needs to be accompanied by an EC roster or letter of compliance, to allow 
verification that the investigator, other site study staff, and/or Medtronic personnel are not members of 
the EC. If they are members of the EC, written documentation is required stating that he/she did not 
participate in the approval process.  Medtronic will prepare the required documents and send them to 
the investigator for reporting to the EC.  Investigators must inform Medtronic of any change in status of 
EC approval once the investigational site has started enrollment.  If any action is taken by an EC with 
respect to the investigation, that information will be forwarded to Medtronic by the respective 
investigator. 

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15.3. Informed consent process and informed consent form 
Prior to enrolling in the study, patients should be fully informed of the details of study participation as 
required by applicable regulations, the site’s EC and by Medtronic. Informed consent must be obtained 
from each patient or legally authorized representative prior to conducting any protocol-induced 
activities beyond standard of care, by using the informed consent form (ICF) approved by that site’s EC 
and by Medtronic. The ICF must be signed and dated by the patient or legal representative and by the 
investigator or authorized designee obtaining the consent.  Any additional persons required by the site’s 
EC to sign the ICF must also comply. 
Prior to the patient or legal representative signing the ICF, the investigator or authorized designee will 
fully explain to the patient or legal representative the nature of the research, study procedures, 
anticipated benefits, and potential risks of participation in the study. The language used shall be in the 
patient’s native language, as non-technical as possible and must be understandable to the patient and 
legal representative, where applicable. The investigator or delegate will allow adequate time for the 
patient or legal representative to read and review the consent form and to ask questions.  
Neither the investigator, nor the investigation site staff shall coerce or unduly influence a subject to 
participate or to continue to participate in the clinical study.  The informed consent process shall not 
appear to waive the subject’s rights. 
Signing the ICF serves to document the written and verbal information that the investigator or 
authorized delegate provides to the patient or legal representative, the patient or legal representative’s 
understanding of the information, and their agreement to participate. The ICF must be signed and 
personally dated by the subject and investigator or authorized designee. The investigator or authorized 
delegate must document in the patient’s medical records that the patient was consented and the date 
on which the consent was obtained. The original signed consent form will be retained in the patient’s 
study records and a copy of the informed consent will be provided to the patient or legal representative.  
The principal investigator or his/her authorized designee will provide a patient with a patient study ID 
card during the informed consent process.  The patient shall use the card to inform doctors/nurses who 
are not involved in the clinical study in case of unscheduled visits or an emergency treatment. 
No patients from a vulnerable population will be included into the study. In addition, due to the nature 
of the eligibility criteria of the study, waiver of prior informed consent process due to emergency 
treatments is not applicable in this study.  
Revision for Informed Consent Form 
As directed by the regulatory authorities, EC or Medtronic, subjects may have to be re-consented to new 
revisions of the informed consent throughout the duration of the study. 
Medtronic will inform the investigators whenever information becomes available that may be relevant 
to the subject’s confirmed participation in the study. The investigator or his/her designee should inform 
the subject in a timely manner. 
Medtronic will revise the written ICF whenever new information becomes available that may be relevant 
to the subject’s confirmed participation in the study. The revised information will be sent to the 

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investigator for EC approval. After approval by the EC, a copy of this information must be provided to 
the participating subjects, and the informed consent process as described above needs to be repeated. 
16. Provisions for reporting of adverse event and equipment 
deficiencies 
Throughout the course of the study, investigational centers will make all efforts to remain alert to 
possible reportable adverse events (AEs) or untoward findings. The study personnel will elicit reports of 
AEs from the subject at each visit (including phone calls) documenting the medical diagnosis, date of 
event start and end, causality (relationship to device or procedure), treatment, outcome, and 
description that includes the details of the event.  The Investigator will determine if an adverse event is 
serious and device/procedure related.  
Pre-existing medical conditions or symptoms reported prior to written informed consent signed are not 
an adverse event (AE), therefore they will be recorded in medical history form. After written informed 
consent signed, if there is no worsening in the pre-existing medical conditions or symptoms, the out-
patient visit for regular follow up and/or medication replenishment or adjustment will not be reported 
as an AE. Investigators will be responsible for the clinical assessment/medical judgment and document 
the none worsening conditions or symptoms for each visit. If the investigator determines any worsening 
in conditions or symptoms, an AE will be recorded. 
Medtronic uses the definitions provided in National Medical Products Administration (NMPA, formerly 
CFDA) China GCP 202223, ISO 14155:2011 for AE definitions. ISO14155:2011 definitions are used for AE 
classifications while expedited reporting to local authorities/EC should be done based on local 
definitions of local regulations.) Medtronic follows MEDDEV 2.3/3 revision 3 guidelines for classifying 
causality levels; but will apply these causality definitions across all events, not only serious adverse 
events and definitions have been adapted accordingly. 
16.1. Adverse event (AE) 
Adverse Event (AE) (ISO 14155-2011) 
Any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including 
abnormal laboratory findings) in subjects, users or other persons, whether or not related to the 
investigational medical device. 
Note 1:  
This definition includes events related to the investigational medical device or the 
comparator. 
Note 2:  
This definition includes events related to the procedures involved. 
Note 3:  
For users or other persons, this definition is restricted to events related to 
investigational medical devices. 
Adverse Event (AE) (NMPA Order No.25 Article 93) 

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Untoward medical occurrence during the clinical study, whether or not related to investigational 
medical devices. 
 
Adverse Device Effect (ADE) (ISO 14155-2011) 
Adverse event related to the use of an investigational medical device.  
Note 1: 
This definition includes adverse events resulting from insufficient or inadequate 
instructions for use, the deployment, the implantation, the installation, the operation, 
or any malfunction of the medical device. 
Note 2:  
This definition includes any event that is a result of a use error or intentional misuse of 
the investigational device. 
16.2. Serious adverse event (SAE) 
Serious Adverse Event (SAE) (ISO 14155-2011) 
An adverse event that  
• 
Led to a death 
• 
Led to a serious deterioration in the health of the subject, that either resulted in 
1. life threatening illness or injury, 
2. a permanent impairment of a body structure or a body function 
3. in-patient* or prolonged hospitalization, or 
4. medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to a body structure or a body function  
Led to fetal distress, fetal death or a congenital abnormality or birth defect *Inpatient Hospitalization is 
defined as: admission to the hospital for a period of 24 hours or more based on urgent medical need 
rather than elective admission. 
Note 1:  
A planned hospitalization for pre-existing condition, or a procedure required by the CIP, 
without a serious deterioration in health, is not considered to be a serious adverse 
event. 
Note 2:  
The term “life-threatening” in the definition of “serious” refers to an event in which the 
patient was at risk of death at the time of the event; it does not refer to an event which 
hypothetically might have caused death if it were more severe. (ICH Topic E 2 A Clinical 
Safety Data Management: Definitions & Standards for Expedited Reporting. EMEA 2006) 
Serious Adverse Event (SAE) (China GCP 2022 Article 64) 

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Any untoward medical occurrence during the clinical study: results in death or serious deterioration in 
health; life-threatening diseases or injuries; causing permanent damage to the body structure or 
function; requires hospitalization or prolongation of hospitalization; requires medical measures to 
prevent from persistent or significant disability/incapacity; results in fetal distress, fetal death, or 
congenital anomaly/birth defect. 
Serious Adverse Device Effect (SADE) (ISO 14155-2011) 
Adverse device effect that has resulted in any of the consequences characteristic of a serious adverse 
event 
Unexpected Serous Adverse Device Effect (USADE) (ISO 14155-2011)  
Serious adverse device effect which by its nature, incidence, severity or outcome has not been identified 
in the current version of the risk analysis report.  
NOTE Anticipated serious adverse device effect (ASADE) is an effect which by its nature, incidence, 
severity or outcome has been identified in the risk analysis report. 
16.3. Device Deficiency (DD) 
Device Deficiency (ISO 14155-2011) 
Inadequacy of a medical device with respect to its identity, quality, durability, reliability, safety or 
performance.  
NOTE: Device deficiencies include malfunctions, use errors, and inadequate labeling. 
Device Deficiency (China GCP 2022 No.28 Article 64) 
Any unreasonable risk caused by a medical device in normal use during clinical trial that may endanger 
human health or life safety, such as label error, quality issues, malfunction and etc. 
16.4. Causality Assessment 
An event is not automatically related to the study device or procedure simply because the subject is 
wearing the device and participating in the study. The event should be reviewed to determine if the 
device or study procedure could have possibly caused the event and therefore is related to the study 
device or procedure.  
Causality assessment is the determination of the relationship between an event and the device being 
studied.  It is expected that the investigational center will review all elements surrounding the event to 
properly assess the causality of the event to the study device (TAV), the TAVR delivery system, the 
loading system or to a study TAVI implant procedure.  
Guidelines for classifying causal relationships between the event and the TAV, the delivery catheter 
system and the TAVR implant procedure is provided in APPENDIX V: DEFINITIONS: SAFETY ENDPOINTS 
AND EFFICACY EVENTS, Section 4.0 Classification of Causal Relationships. In addition to classifying causal 
relationships, sites are to provide a cause analysis for each event.  

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16.5. Anticipated or Unanticipated 
If the AE is determined to be related to the study device the sponsor will then assess the event to 
determine if it is anticipated or unanticipated. 
• 
Anticipated: the event is identified in the CIP; labeling; IB or IFU. 
• 
Unanticipated: the event has not been previously identified in the CIP; labeling; IB or IFU. 
16.6. Evaluation and Documentation of Adverse Events 
Investigators are required to evaluate and document all adverse events (AE) and device deficiencies (per 
the definitions above) observed in study subjects throughout the study duration, starting at the time of 
written informed consent signed. All AEs that occur during the study need to be reported to Medtronic 
via the AE eCRF. All AE should be followed through their resolution or until subject’s study exit.  
Medical occurrences that are inherent to a TAVR procedure and expected to occur in the majority of 
subjects for a projected duration may be considered unavoidable. The events listed in Table 4 are 
expected for patients undergoing TAVR, and do not need to be reported as AE; unless they occur outside 
of the stated timeframe, are otherwise considered need to be reported according to the treating 
investigator, or are suspected or confirmed to be device-related. 

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Table 4. Non-reportable medical occurrences associated with index implant procedure 
Event 
Timeframe (hours) from 
the Index Procedure 
Short transient episode of arrhythmia (including ventricular fibrillation) 
during index procedure 
0 
Confusion, anxiety and/or disorientation (other than TIA/stroke) starting 
within 48 hours with or without medical intervention 
120 (5 days) 
Temporary change in mental status (other than TIA/stroke) not requiring 
additional medical interventions or new medical assessments (e.g., CT) 
72 
Dizziness and/or lightheadedness with or without treatment  
24 
Headache with or without treatment 
72 
Sleep problems or insomnia with or without treatment 
120 (5 days) 
Mild dyspnea or cough with or without treatment 
72 
Oxygen supply after extubation/“forced breathing therapy” 
48 
Diarrhea with or without treatment 
48 
Obstipation/Constipation with or without treatment 
72 
Anesthesia-related nausea and/or vomiting with or without treatment  
24 
Low-grade fever (<101.3°F or <38.5°C) without confirmed infection 
48 
Low body temperature 
6 
Pain (e.g., back, shoulder) related to laying on the procedure table with 
or without treatment 
72 
Incisional pain (pain at access site) with or without standard treatment 
and patient not returning to clinic to have additional treatment 
72 
Pain in throat and/or trachea due to intubation 
72 
Mild to moderate bruising or ecchymosis at access site(s) as determined 
by physician 
168 (7 days) 
 
For all observed AEs, investigators should assess and document the following information on the 
Adverse Event eCRF: 
• 
Date of onset or first observation 
• 
AE code number 
• 
AE term 
• 
Description of the event 
• 
Date of site’s first knowledge of the event 
• 
Seriousness of the event 
• 
Causal relationship of the event to the Evolut PRO TAV 
• 
Causal relationship of the event to the DCS 
• 
Causal relationship of the event to the LS 

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• 
Causal relationship of the event to the implant procedure 
• 
Event cause analysis  
• 
Treatment required 
• 
Outcome or status of the event 
• 
Date of resolution 
In addition, sites should submit relevant source documents to Medtronic for the Clinical Events 
Committee (CEC) members to use in their adjudication for all surgical or catheter-based intervention on 
the Evolut PRO, deaths, and safety endpoint events. Definitions of safety endpoints, and guidelines for 
accessing causal relationships are provided in APPENDIX V: DEFINITIONS: SAFETY ENDPOINTS AND 
EFFICACY EVENTS. The AE code list will be provided under a separate cover.  
16.7. Reporting procedures and information of contact 
16.7.1. 
Reporting of Adverse Events 
The Investigator or designee will record all AEs since the time of written informed consent signed in the 
clinical study. Each AE needs to be assessed for its device or procedure relatedness.  Investigators should 
provide continuous monitoring, assessment and documentation of the events throughout the duration 
of the study. 
Baseline medical conditions should only be reported to sponsor on an AE eCRF if there is a worsening 
from the subject’s baseline.  For example, a subject previously diagnosed with asthma is hospitalized for 
severe asthma attack would be a reportable event. 
Adverse events will be documented in the subject source file and reported to sponsor on an eCRF. The 
investigational center is responsible for documentation of AEs including obtaining source documents 
related to the event, such as hospital records (admission summary; lab results, test results, discharge 
summary) or device operation reports to support the event if possible. Source documents will be 
reviewed to determine if additional AEs have occurred and require reporting. 
How long to follow an AE (AEs should be followed until one of these criteria is met): 
• 
Until the AE resolves 
• 
Until no further action can be taken for an ongoing AE 
• 
Until the subject exits the study, or 
• 
Until study closure 
NOTE: In the case of permanent impairment, continue to follow the event until it stabilizes, and the 
overall clinical outcome has been ascertained. 
Adverse events that have not resolved at the time of the subject’s discontinuation or completion of the 
study should have an “outcome” of Not Recovered/Not Resolved at study end in subject source and on 
an eCRF. The investigator should ensure that subject is aware of any follow-up or additional treatment 
that is required for any ongoing AE at end of study participation; however, there will be no eCRF entry 
for the ongoing follow-up. 

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16.7.2. 
Notification of Adverse Events 
Sponsor Notification: 
Initial reporting may be done by phone, fax, e-mail, or on the eCRF completing as much information as is 
available. The original fully completed AE eCRF must be submitted to Medtronic as soon as possible. 
As soon as possible (desired within 24 hours of investigator or study coordinator awareness), the 
investigational center staff must report all SAE, and SADE to Medtronic. For the previously mentioned 
events, the AE eCRF will be completed with all known details as soon as possible, this will serve as 
notification to Medtronic. If the study database cannot be accessed due to technical problems, contact 
the sponsor via email, phone, fax and provide the known details of the event. Once the access issue has 
been corrected, the event should be entered onto an AE eCRF. 
16.7.3. 
Expedited Safety Reporting Requirements 
Documentation of GCP office and EC notification of any safety event must be kept at the investigational 
center and a copy sent to the sponsor. 
It is the responsibility of the investigator to follow their EC reporting requirements. 
Timeframes and mechanisms for the clinical site reporting adverse events to EC, and Medtronic per 
NMPA GCP for Medical Devices23 (China GCP 2022) are listed in Table 5. 
 
 

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Table 5. Investigator Reporting Requirements for AE and Device Deficiencies 
For the following events, reporting requirements are: 
• 
Serious Adverse Events (SAE) 
Investigators shall report to (China GCP 2022 Article 32): 
Medtronic 
Within 24 hours 
GCP office 
Within 24 hours 
EC 
Within 24 hours 
For the following events, reporting requirements are: 
• 
All other AEs 
• 
All Device Deficiencies 
Investigators shall record adverse events and device deficiencies identified during clinical trials of 
medical devices. (China GCP 2022 Article 31) 
To Medtronic 
Submit AE and DD in a timely manner after the 
investigator first learns of the event. 
To EC and GCP office 
Submit event analysis report per EC’s requirements  
NOTE: In case there is/are additional AE reporting requirement(s) and/or process(es) (e.g. internal 
hospital policy or province regulatory authority instruction, etc.), these specific AE reporting requirement 
and process must be documented in a separate cover. 
Timeframes and mechanisms for the sponsor submitting adverse events to local regulatory authorities 
and other clinical Research institutions and investigators participating in the study per the NMPA GCP 
for Medical Devices23 (China GCP 2022) are listed in Table 6. 
Table 6. Sponsor Reporting Requirements for AE and Other Serious Safety Issues 
For the following events, reporting requirements are: 
• 
Investigational device related Serious Adverse Events (SAE) 
• 
Other serious safety issues that led to clinical study suspension or termination. 
Medtronic submits to: 
(China GCP 2022 Article 44) 
The drug regulatory departments 
in the province, autonomous 
region or municipality directly 
under the Central Government 
where the sponsor is located 
Within 7 days after learning that serious adverse events related 
to death or life-threatening serious adverse events occur on the 
medical device under clinical trial.  
Within 15 days after learning that serious adverse events not 
related to death or non-life-threatening serious adverse events 
occur on the medical device under clinical trial and the medical 
device under clinical trial may have other serious safety risks. 
Submit Large scale investigational device related SAEs or other 
serious safety issues that led to clinical study suspension or 
termination. 

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For the following events, reporting requirements are: 
• 
Investigational device related Serious Adverse Events (SAE) 
• 
Other serious safety issues that led to clinical study suspension or termination. 
The drug regulatory departments 
and health administration 
departments in the provinces, 
autonomous regions or 
municipalities directly under the 
Central Government where the 
clinical trial institutions of the 
medical device are located 
Within 7 days after learning that serious adverse events related 
to death or life-threatening serious adverse events occur on the 
medical device under clinical trial.  
Within 15 days after learning that serious adverse events not 
related to death or non-life-threatening serious adverse events 
occur on the medical device under clinical trial and the medical 
device under clinical trial may have other serious safety risks. 
Submit Large scale investigational device related SAEs or other 
serious safety issues that led to clinical study suspension or 
termination. 
Other clinical trial institutions of 
the medical device involved in 
the clinical trial  
Within 7 days after learning that serious adverse events related 
to death or life-threatening serious adverse events occur on the 
medical device under clinical trial.  
Within 15 days after learning that serious adverse events not 
related to death or non-life-threatening serious adverse events 
occur on the medical device under clinical trial and the medical 
device under clinical trial may have other serious safety risks. 
Submit Large scale investigational device related SAEs or other 
serious safety issues that led to clinical study suspension or 
termination.  
Other Ethics Committees 
involved in the clinical trial  
Within 7 days after learning that serious adverse events related 
to death or life-threatening serious adverse events occur on the 
medical device under clinical trial.  
Within 15 days after learning that serious adverse events not 
related to death or non-life-threatening serious adverse events 
occur on the medical device under clinical trial and the medical 
device under clinical trial may have other serious safety risks. 
Submit Large scale investigational device related SAEs or other 
serious safety issues that led to clinical study suspension or 
termination. 
Other principal investigators 
involved in the clinical trial 
Within 7 days after learning that serious adverse events related 
to death or life-threatening serious adverse events occur on the 
medical device under clinical trial.  
Within 15 days after learning that serious adverse events not 
related to death or non-life-threatening serious adverse events 
occur on the medical device under clinical trial and the medical 
device under clinical trial may have other serious safety risks. 

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Clinical Investigation Plan  
 
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For the following events, reporting requirements are: 
• 
Investigational device related Serious Adverse Events (SAE) 
• 
Other serious safety issues that led to clinical study suspension or termination. 
Submit Large scale investigational device related SAEs or other 
serious safety issues that led to clinical study suspension or 
termination. 
NOTE: In case there is/are additional AE reporting requirement(s) and/or process(es) (e.g. internal 
hospital policy or province regulatory authority instruction, etc.), these specific AE reporting requirement 
and process must be documented in a separate cover. 
Documentation and Reporting of Device Deficiencies 
Device deficiency information will be collected throughout the study and reported to Medtronic. Device 
deficiencies that led to an AE are reported on the AE eCRF. Device deficiencies that did not lead to an AE 
should be reported on a Device Deficiency eCRF (one for each Device deficiency). 
Device deficiencies that did not lead to an adverse event but might have led to a SADE if:  
• 
a suitable action had not been taken, or  
• 
an intervention had not been made, or  
• 
circumstances had been less fortunate,  
should be reported to Medtronic as soon as possible after the investigator first learns of the event. 
Initial reporting may be done by phone, fax, e-mail, or on the eCRF completing as much information as is 
available. The original fully completed Device Deficiency eCRF must be submitted to Medtronic as soon 
as possible. 
 
 

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Emergency Contact Details for Reporting SAE, SADE and Device Deficiencies 
Investigators should contact their Medtronic clinical study monitor if they have any questions regarding 
reportable AEs. Medtronic will provide and maintain a listing of current contact details for each site. In 
case the investigator requires information from Medtronic in an emergency situation, the investigator 
may contact Medtronic.  A list of contact information will be kept separately. 
17. Provisions for clinical study protocol deviation and the 
revision of clinical study protocol  
17.1. Protocol Deviations 
A deviation is any instance(s) of failure to follow, intentionally or unintentionally, the requirements of 
the CIP. It is expected that the investigator will conduct this clinical trial in compliance with the CIP and 
all applicable regulations governing the conduct of clinical research involving human subjects. Failure to 
do so could result in one or all of the following: 
• 
Investigational center disqualification  
• 
Notification to the regulatory authorities/EC depending on the severity of the deviation and 
reporting requirements 
Examples of protocol deviations include but are not limited to the following: 
• 
Failure to obtain informed consent prior to participation 
• 
Incorrect version of the informed consent form used 
• 
Failure to obtain EC approval before the start of the study 
• 
Implanted subject did not meet inclusion or met exclusion criteriavi 
• 
Required testing and/or measurements not done or incorrectly done 
• 
Subject does not attend follow-up visit or follow-up visit performed outside window 
• 
Unauthorized use of investigational devices 
• 
Adverse events not reported in the required time frame as required by regulation, the site’s EC, 
or as specified in the Clinical Investigation Plan (CIP) 
• 
Control of study devices not maintained 
• 
Source data permanently lost 
• 
Enrollment of patients during lapse of EC approval 
Investigators should obtain prior approval from Medtronic before initiating any change or deviation 
from the CIP, except where necessary to protect the life or physical wellbeing of a subject in an 
emergency situation. Such approval shall be documented in writing and maintained in the Investigator 
Site File. Prior approval is generally not expected in situations where unforeseen circumstances are 
beyond the investigator’s control (e.g., subject did not attend scheduled follow-up visit). 
 
vi Subjects must meet all inclusion/exclusion criteria to be eligible for implantation.  However, it will not be considered a protocol deviation if 
study related testing (e.g., echo, MDCT, Heart Team Assessment) of a consented patient identifies implantation eligibility criteria that are not 
met. 

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Deviations will be reported to Medtronic regardless of whether medically justifiable, pre-approved by 
Medtronic, or taken to protect the subject in an emergency. Study deviations should be reported to 
Medtronic via the Protocol Deviation eCRF (one eCRF for each protocol deviation).  
Investigators should report the following deviations to Medtronic and their reviewing EC within 5 
working days of the occurrence of the deviations:  
• 
Failure to obtain written informed consent 
• 
Deviations to protect the life or physical well-being of a subject in an emergency 
In addition, investigators are required to adhere to their EC procedures for reporting deviations. 
Medtronic is responsible for analyzing deviations, assessing their significance, and identifying any 
corrective and/or preventive actions that may be warranted. Repetitive or serious investigator 
compliance issues may represent a need to initiate a corrective action plan, which may include 
suspension of enrollment or termination of the investigator’s or site’s participation in the study. 
17.2. Revisions or Amendments to the Clinical Investigational Plan 
The investigator may propose any appropriate modification(s) of the CIP or investigational device or 
investigational device use. Medtronic will review this proposal and decide whether the modification(s) 
will be implemented.  
Medtronic will submit any significant amendment to the CIP, including a justification for the 
amendment, to the appropriate regulatory authorities (if applicable) and to the investigators to obtain 
approval from their EC. The investigator will only implement the amendment after approval of the EC, 
regulatory agency (if applicable) and Medtronic. Administrative amendments to the CIP will be 
submitted to the EC for notification. Furthermore, investigators shall sign any approved amendment for 
agreement.  
18. Record Retention 
The sponsor and investigator will retain all records and documents pertaining to this study in compliance 
with local regulations. They will be available for inspection by the appropriate regulatory agencies. In 
addition, the investigator will retain the source documents from which the information entered on the 
eCRF was derived. These records are to be retained in a secure storage facility maintained by the 
investigational center for 10 years after completion of the study or termination of the study, whichever 
is longer. The investigator should not dispose of these records without the approval of the sponsor. The 
investigator should take measures to prevent accidental or early destruction of the clinical study related 
materials. The sponsor shall keep the clinical data indefinitely and till no such medical device is used. 
In addition, the Medtronic Clinical Research Department should be contacted if the Principal 
Investigator plans to leave the investigational site. 
Investigator may withdraw responsibility to maintain records for the time required by the study protocol 
by transferring custody to another qualified person willing to accept responsibility for them. Medtronic 
will report this change within 10 days to the relevant regulatory authorities as necessary. 

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Medtronic will maintain study records under its responsibility until Evolut PRO is no longer commercially 
used, or at least 15 years, whichever is longer. 
19. Suspension or Early Termination 
19.1. Investigational Center Suspension or Termination 
Medtronic, EC, or a regulatory authority may decide to suspend or prematurely terminate an 
investigational center (e.g. if information becomes available that the risk to study subject is higher than 
initially indicated, business decision, in case of expiring approval of the reviewing EC, non-compliance to 
the CIP or lack of enrollment). The medical device clinical trial management departments of clinical trial 
institutions should be notified within 5 days with the rationale in writing. If an investigational center is 
suspended or prematurely terminated, Medtronic shall promptly inform the investigator(s) of the 
termination or suspension and the reason(s) for this. The investigator shall then promptly inform the 
reviewing EC and the study subjects.  
Clinical study institutions and the researchers discover that risks outweigh potential benefits or have 
obtained sufficient results to determine the safety and effectiveness of the testing medical devices, 
when it is required to suspend or terminate clinical studies, they shall inform the testing subjects, and 
assure them with proper treatment and follow-ups, meanwhile report as required, and provide detailed 
written explanation. When necessary, they shall report to the department of NMPA of the concerned 
province, autonomous region and municipality.  
Upon receiving notifications that the applicant or ethics committee need to suspend or terminate 
clinical studies, the researchers shall timely notify the testing subjects, and assure them with proper 
treatment and follow-ups. 
The suspended clinical studies cannot be resumed without permission from EC. Upon completion of 
clinical studies, the applicant shall send written notice to the management of food and drug 
administration of the concerned province, autonomous region and municipality 
Medtronic shall ensure that all investigators who conduct the clinical study comply with the clinical 
investigation plan. In case a clinical research institution and an investigator are found failed to comply 
with relevant laws and regulations, China NMPA Good Clinical Practice for Medical Devices (China GCP 
2022) 23 and this clinical investigation plan, Medtronic shall identify it and implement a course of 
corrective actions. For serious case or continued case without rectification, Medtronic should terminate 
the study at this clinical research institution and notify the local Food and Drug Administration 
(province, autonomous region or municipality as appropriate) where this clinical research institution 
locates and NMPA. 
19.2. Subject Follow-Up In Case of Termination 
In case of early investigational center suspension or termination, all subjects should be contacted to 
plan an early Termination visit at the investigational center. All efforts will be made to complete and 
report all study observations at the time of termination. The subject will receive appropriate treatment 
and follow-up as per local standard of care.  

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20. Direct access to source data/documents 
Source Data/Document Access 
Entered data must be traceable to source documents. Source documentation is defined as the first time 
the data appear and may include clinical records, hospital records, procedural reports, autopsy reports, 
and any other material that contains original information used for study data collection or adverse event 
reporting. 
The eCRFs may not serve as source documents. Source documentation for data elements not routinely 
captured in medical records (e.g., echocardiography variables, Modified Rankin Score) may vary from 
site to site: the site may use technical worksheets if identified as source documents. 
The investigator must ensure the availability of source documents from which the information on the 
eCRFs was derived. Direct access to subject medical files for source data verification will need to be 
granted and prepared prior to any monitoring visits. 
20.1. Investigator Records 
At a minimum, the following records must be kept by the investigator: 
• 
All essential study documents and correspondence that pertains to the clinical study 
• 
CIP and, if applicable, any amendments 
• 
Investigator’s Brochure and/or user guide 
• 
Medtronic and EC-approved Patient ICF 
• 
EC and Regulatory authority approval or notification 
• 
Fully signed clinical study agreements (i.e. including Investigator Statement and Signature Page, 
Clinical Trial Agreement and Confidential Disclosure Agreement) 
• 
Completed Delegation of Authority Log  
• 
Training documentation of all investigational center staff 
• 
Subject screening log and/or subject identification (SID) log  
• 
Signed, dated and fully executed ICFs 
• 
Source document requirements 
• 
Fully executed eCRFs and corrections  
• 
Report of AEs and Device Deficiencies 
• 
Device accountability records 
• 
CIP Deviation/ CIP Non Compliance, if any 
• 
Clinical Bulletins- A brief official update or summary of current study news on a matter of immediate 
interest and high importance to investigational center surrounding the CIP. 
• 
Current signed and dated curriculum vitae (CV) of PI (and key study team members if required per 
local requirements) 
• 
Site-specific summary or Clinical Study Reports (CSRs) 

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20.2. Investigator Reporting Responsibilities 
The Investigator reporting requirements are listed in Table 7. 
 
Table 7. Investigator Reporting Requirements 
Report 
Submit to 
Description/Constraints 
Protocol 
deviation 
 
Sponsor, Management 
department of medical 
device clinical study (if 
required), EC 
Any deviation from the clinical investigational plan shall be 
recorded together with the explanation of the deviation. 
Protocol deviation that may affect the subjects’ rights and 
interests, safety, health or the scientificity of clinical trials, 
including deviation regarding requests and reports. 
Principal investigators shall report any deviation from the 
clinical trial protocol in time.  
(China GCP 2022 Article 34) 
Failure to 
obtain 
informed 
consent 
Sponsor and EC 
Informed consent shall be obtained in writing and documented 
before a subject is enrolled into the clinical investigation.   
(ISO 14155:2011) 
Progress 
report 
EC and Management 
department of medical 
device clinical study (if 
required)  
Principal investigators shall report the progress of clinical trials 
of medical devices to the Ethics Committee on time. 
(China GCP 2022 Article 34) 
Site-
specific 
summary 
Sponsor,  EC (if needed 
per EC requirements)  
For multi-center studies: 
The site-specific summary of each sub-center shall be signed 
and dated by the principal investigator of the center, reviewed 
and signed by the clinical trial institution of medical device of 
the center, and then submitted to the sponsor. The site-specific 
summary of clinical trials in sub-centers mainly includes 
personnel information, information of investigational medical 
devices and control medical devices (if applicable), trial 
overview, case inclusion, implementation of clinical trial 
protocol, summary and descriptive analysis of trial data, quality 
management of clinical trials of medical devices, occurrence 
and treatment of adverse events and device deficiencies, 
description of deviation from the protocol, etc. 
(China GCP 2022 Article 56)  
Other 
EC and NMPA 
An investigator shall, upon request by a reviewing EC, NMPA or 
any other regulatory agency, provide accurate, complete, and 
current information about any aspect of the investigation. 
 
20.3. Audits and Inspections 
Medtronic may conduct audits at participating clinical sites.  The purpose of an audit is to assess clinical 
study activities independently of the personnel directly involved in the study.  Regulatory authorities, 
such as the NMPA, and ECs may also perform inspections at participating sites.  The investigator and/or 

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institution shall permit Medtronic and Regulatory Authority direct access to source data and documents.  
Any Regulatory Authority inspection announcements shall be forwarded immediately to the Medtronic 
Clinical Study Manager of this study.  A list of contact information will be kept separately. 
21. Finance and insurance 
If subjects are physically injured as a result of participation in this study, reasonable and appropriate 
medical treatment will be provided by Medtronic, if such treatment is not already covered by subject’s 
medical insurance according to the local requirements.  The sponsor shall undertake treatment 
expenses and corresponding economic compensation for injuries or death related to clinical studies 
occurred to testing subjects, except the damage due to mistakes of the medical institutions and their 
medical staff during diagnosis and treatment, if not addressed in a separate agreement. 
Medtronic maintains appropriate clinical study liability insurance coverage as required under applicable 
laws and regulations and will comply with applicable laws and customs concerning specific insurance 
coverage.  If required, a Clinical Study Insurance statement/certificate will be provided to the EC. 
21.1. Clinical Investigation Agreement 
A Clinical Investigation Agreement shall be entered into effect by the participating site and/or the 
principal clinical investigator at each site as per the local legal requirements and returned to Medtronic 
prior to the commencement of any study activities. The investigator is indicating approval of the 
Protocol and subsequent amendments, by signing and dating the agreement. Amendments to this 
protocol shall be agreed upon between Medtronic and clinical investigator(s) and be recorded with a 
justification for the amendments. 
Funding for the study will be defined according to the local regulations and must be agreed upon in 
writing by the clinical research institution and Medtronic before the study commences. The payments 
for the study should be appropriate relative to the number of subjects enrolled. The Evolut PRO System 
will be provided by Medtronic free of charge for use in this clinical study. A reasonable amount of the 
travel expense for the annual clinic follow-up will be reimbursed. The cost of the medical check-ups 
which are required by the study will be reimbursed as well. No other compensation for the participation 
in this study will be provided by Medtronic. 
 
 

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22. Contents included in the clinical study report 
The Clinical Study Reports (CSR) shall reflect the clinical trial results comprehensively, completely and 
accurately, and the data of safety and effectiveness of the clinical trial report shall be consistent with the 
source data of the clinical trial as described in NMPA China GCP 202223 and compliant with NMPA China 
GCP 2022 Appendix 2 “Template of Clinical Study Report of Medical Devices”. Any deviations from 
original statistical plan and the rationale will be described in the Clinical Study Report.  
Primary endpoint CSR and subsequent CSRs, along with the CIP, may support the new generation(s) of 
study devices being commercially available. 
23. Confidentiality principle 
Subject confidentiality will be maintained throughout the clinical study in a way that ensures the 
information can always be tracked back to the source data.  All information and data sent to parties 
involved in study conduct concerning subjects or their participation in this study will be considered 
confidential. Study sites will assign a unique subject ID number (SID) to each subject. Records of the 
subject/SID relationship will be maintained by the study site. The SID is to be recorded on all study 
documents to link them to the subject’s medical records at the site. To maintain confidentiality, the 
subjects’ name or any other personal identifiers should not be recorded on any study document other 
than the informed consent form. In the event a subject’s name is included for any reason, it will be 
masked as applicable. In the event of inability to mask the identification (e.g., digital media), it will be 
handled in a confidential manner by the authorized personnel. 
Study data may be made available to third parties, e.g., in the case of an audit performed by regulatory 
authorities, provided the data are treated confidentially and that the subject’s privacy is guaranteed.  
The identity of a subject will never be disclosed in the event that study data are published. 
24. Agreement on trial results publication 
This clinical study will be registered in a public clinical trials registry, ClinicalTrials.gov. Study information 
and study results will be posted. Medtronic is committed to the widespread dissemination of all primary 
and secondary endpoint results. A Publication Plan will be implemented and followed. During the course 
of or at the conclusion of the study, a multisite abstract reporting the primary results may be prepared 
by the Principal Investigators (in collaboration with others including but not limited to the echo core lab 
physicians and the Clinical Events Committee (CEC)). A multisite publication may similarly be prepared 
for publication in a reputable scientific journal. The publication of the principal results from any single 
site experience within the study is not allowed until both the preparation and publication of the 
multisite results, and then only with written permission from Medtronic. 

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25. Responsibilities of all parties 
Investigator responsibilities will be included in clinical trial agreement and subject responsibilities will be 
available in Informed Consent Form (ICF). Sponsor will undertake all the responsibilities of the sponsor 
as required per NMPA regulations. 
26. Data Review Committees 
26.1. Clinical Events Committee 
A Clinical Events Committee (CEC) will provide independent medical review and adjudication of adverse 
event data used in the endpoint assessment of the investigational device. The CEC will adjudicate all 
deaths, and all endpoint related events reported by the investigators.  The analysis of the study 
endpoint data will be based on CEC adjudicated events.  Endpoint definitions are provided in APPENDIX 
V: DEFINITIONS: SAFETY ENDPOINTS AND EFFICACY EVENTS. 
The CEC members will be free from bias towards the study and will be independent from both the study 
and investigators and Medtronic. The committee will consist of at least 3 independent experts (non-
Medtronic employed physicians) with expertise relevant to the study. This may include experience in the 
areas of: 
• 
Cardiac surgery 
• 
Interventional cardiology 
• 
Neurology 
• 
Electrophysiology 
A CEC charter will be established that describes the Committee roles, responsibilities, and processes.   
27. Appendices 
I.Names and Addresses of Investigational Centers  
II.Echocardiography Procedures 
III. MDCT Acquisition Guidelines 
IV. STS Calculator and Risk Factors 
V. Definitions: Safety Endpoints and Efficacy Events 
VI.Study contacts 
VII. Sample informed consent form 
 
 

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APPENDIX I: NAMES AND ADDRESSES OF INVESTIGATIONAL 
CENTERS  
List of all clinical trial institutions and investigators for multicenter clinical trial: 
Code of clinical trial 
institution 
Name of clinical trial 
institution 
Investigator 
Title 
Contact 
information 
The list of all clinical trial institutions and investigators will be provided separately in the 
Investigational Site File (ISF). 
 
 
 
 

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APPENDIX II: ECHOCARDIOGRAPHY PROCEDURES 
1.0 
Required Exams 
Transthoracic echocardiography is required at the following intervals: 
Interval 
Time Window 
Baseline (Pre-implant) 
Within 12 weeks prior to Eligibility Review Committee review 
Device Success 
Between 24 hours and 7 days post procedure 
30 days 
Between 30 and 45 days post procedure 
1 year 
Between 365 and 395 days post procedure 
Annual up to 5 years 
Between implant anniversary date and 30 days after 
2.0 
General Imaging and Recording Procedures 
• 
A list of recommended images is provided in Section 2.1. 
• 
The subject’s ID number and exam interval should be annotated on the image. 
• 
A simultaneous ECG with a clearly defined R-wave should be displayed on all clips. 
• 
Digital cine clips should be a minimum of two cardiac cycles in length (preferably three cycles) 
• 
Color Doppler images should be obtained at a minimum frame rate of 20 Hz through optimization of 
sector width and depth settings. 
• 
Still frames of measured variables (e.g., LVOT diameter, velocities) should be captured. In addition, 
still frames of spectral Doppler tracings without the measurements should be captured to facilitate 
analysis by the Echo Core Lab. Still frames of spectral Doppler tracings should contain a minimum of 
3 cardiac cycles for subjects in sinus rhythm, and a minimum of 5 cardiac cycles for subjects in atrial 
fibrillation (two sequential frames per variable may be necessary). 
• 
Spectral Doppler waveforms should be recorded at a minimum sweep speed of 50 mm/sec. 
• 
Echocardiograms should be recorded and archived on a DICOM digital format for transmission to 
the Echo Core Lab. 
• 
Exams will be transmitted to the Echo Core Lab via compact disc (CD-R) or Web-based picture 
archiving and communication system. Details of the image transmission process for each site will be 
established during site initiation process. 
• 
Exams sent to the Echo Core Lab via CD-R should be DICOM files in a true or pure DICOM format. 
• 
The following information should be documented on CD-R disks sent to the Echo Core Lab: 
- Study site ID number 
- Subject ID number 
- Exam date 
- Study interval 
2.1 List of Recommended Images 
Parasternal long-axis window 
• 
2D gray scale standard view (LV in a sagittal section) 

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• 
2D color Doppler for mitral regurgitation (MR) 
• 
2D color Doppler of aortic (or prosthetic) regurgitation (AR) 
• 
If AR is present, ZOOM & narrow sector with focus on vena contracta of regurgitant jet  
• 
2D gray scale ZOOM for LV outflow tract diameter (LVOT)  
• 
Frozen image of measured LVOT diameter 
• 
2D gray scale; ZOOM at an intercostal space higher for aortic root / aortic prosthesis  
Parasternal short-axis window 
• 
2D grayscale LV at mitral valve level 
• 
2D grayscale LV at papillary muscle level  
• 
2D grayscale-guided M-mode at LV minor axis (LV dimensions, avoid papillary muscles) 
• 
Frozen image of measured LV dimensions (without measurements) 
• 
2D grayscale LV at apical level 
• 
2D grayscale aortic valve level (post TAVI the native annulus is usually identified by maximal 
calcification) 
• 
2D color Doppler of AR: post TAVI start scanning from highest position and record first visible AR 
jet, scan more downwards and look for additional jets – confirm origin of AR jets from PLAX 
Parasternal long-axis view (RV inflow) 
• 
2D color Doppler of tricuspid regurgitation (TR) 
• 
If TR is present, CW Doppler of TR jet (frozen image without measurements) 
• 
Frozen image of TR jet velocity with measurements 
Apical 4-Chamber window 
• 
2D grayscale standard view  
• 
2D color Doppler of MR  
• 
If MR is present, ZOOM & narrow sector, shift Nyquist 35-40 for PISA measurements  
• 
If MR is present, CW Doppler of MR jet (frozen image) 
• 
2D color Doppler of TR 
• 
If TR is present, CW Doppler of TR jet (frozen image without measurement) 
• 
Frozen image of TR jet velocity with measurements 
• 
2D grayscale focussed on LV with decreased depth 
• 
PW Doppler of transmitral flow at mitral valve tips (frozen image) 
Apical long–axis view 
• 
2D grayscale standard view 
• 
2D color Doppler of AR 
• 
If AR is present, ZOOM & narrow sector, shift Nyquist 35-40 for PISA measurements  
• 
If AR is present, CW Doppler of AR jet (frozen image without measurement) 
• 
Frozen image of CW Doppler of AR jet (with measurements) 
• 
CW Doppler of aortic/prosthetic valve (frozen image without measurement) 
• 
Frozen image of measured aortic/prosthetic valve velocity 
• 
PW Doppler LVOT (native aortic valve): within 0.5 – 1 cm below native aortic valve (frozen image 
without measurements 

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• 
PW Doppler LVOT (post –implant) immediately proximal to inflow of stent (frozen image 
without measurements) 
• 
Frozen image: measured LVOT velocity 
Apical 2-Chamber view 
• 
2D grayscale standard view 
• 
2D grayscale focused on LV with decreased depth 
Sub-costal Position 
• 
2D grayscale; long-axis view 
• 
2D grayscale; short-axis view 
• 
2D grayscale: IVC and hepatic vein 
• 
IF AR mild by color Doppler, PW Doppler from descending aorta (frozen image) 
Supra-Sternal Position 
• 
CW Doppler of aortic valve velocity non-imaging probe (frozen image without measurements) 
• 
Frozen image: measured aortic valve velocity 
• 
If AR mild by color Doppler, PW Doppler from descending aorta (frozen image) 
Right Parasternal Position 
• 
CW Doppler of aortic valve velocity; non-imaging probe (frozen image without measurements) 
• 
Frozen image: measured aortic valve velocity 
Results Reporting 
• 
Screen prints of all results pages 
 
 

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3.0 
Data Requirements 
Sites should obtain the appropriate images and Doppler recordings in order for the Echo Core Lab to 
assess and report the variables listed below. Procedures for acquiring key variables are described in 
Section 4, Acquisition of Key Variables. 
• 
Heightvii and Weight  
• 
Left ventricular outflow tract (LVOT) diameter in mid systole 
• 
Max aortic/prosthetic valve velocity (V2) by CW Doppler 
• 
Aortic valve velocity time integral (VTI) by CW Doppler 
• 
Mean gradient across aortic valve (MGV2) by CW Doppler 
• 
LVOT VTI by PW Doppler 
• 
Grade of aortic/prosthetic transvalvular regurgitation  
• 
Grade of prosthetic paravalvular regurgitation (post-implant only) 
• 
Grade of prosthetic total (transvalvular plus paravalvular) regurgitation (post-implant only) 
• 
Grade of mitral regurgitation 
• 
Grade of tricuspid regurgitation 
• 
Max tricuspid regurgitant (TR) jet velocity (if TR is present) 
• 
Left ventricular internal dimension at end diastole 
• 
Left ventricular internal dimension at end systole 
• 
Interventricular septal thickness at end diastole 
• 
Left ventricular posterior wall thickness at end diastole 
• 
Left atrial diameter (anterior-posterior linear dimension) at systole 
• 
Left ventricular ejection fraction 
In addition, the following variables will be derived by the central database from the appropriate 
measurements reported on the site eCRF. 
• 
Body surface area (Dubois and Dubois)31 
• 
Body mass index 
• 
Peak aortic pressure gradient 
• 
Aortic valve area (AVA)/effective orifice area (EOA) by continuity equation 
• 
Aortic valve area/effective orifice area index 
• 
Doppler Velocity Index 
Derived variables will be displayed on the eCRF upon entry of the appropriate raw measurements.  The 
pre- implant qualifying AVA must be based on the site reported variables for LVOT diameter, LVOT VTI, 
aortic valve VTI, height, and weight. 
4.0 
Acquisition of Key Variables 
 
vii Height will be collected at the baseline (pre-implant) exam only.  Height for the post-implant exams will be derived from the 
baseline height 

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4.1 
LVOT Diameter  
Pre-implant LVOT diameter is measured from the inner edge to inner edge of the septal endocardium, 
and the anterior mitral leaflet in mid-systole (Figure 6A and B).33,34  Following implantation, LVOT 
diameter is measured from the parasternal long-axis view, immediately proximal to the inflow aspect of 
the stent, and in mid systole (Figure 6C and Figure 6D).33,34,35 
 
 
Figure 6. Left ventricular outflow tract (LVOT) diameter measurements 
(A) and (B) Examples of measurement of pre-implant LVOT diameter. LVOT diameter is measured from the white-
black interface of the septal endocardium to the anterior mitral leaflet, parallel to the aortic valve plane, 
approximately 0.5 cm below the level of the aortic annulus, and in mid systole; (C) and (D) Post implantation, LVOT 
diameter measurement is from outer edge to outer edge of the inflow aspect of the stent. 
4.2 
LVOT Velocity 

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LVOT velocity is recorded with PW Doppler from the apical position, in either the apical long-axis view or 
in the anteriorly angulated four-chamber view (or “5-chamber view”).  For pre-implant exams, the PW 
sample volume should be positioned just proximal to the aortic valve, with care to avoid the zone of pre-
valve acceleration (usually 0.5 to 1.0 cm proximal to the cusps, Figure 7A).33 
Post TAV implantation, the sample volume should be placed proximal to the inflow aspect of the stent.34 
Full-screen imaging of the Evolut PRO TAV should be used to verify positioning of the sample volume 
below the stent before switching to spectral Doppler mode (Figure 7C and Figure 7D).35,36 The LVOT VTI 
is measured by tracing the modal velocity (middle of the dense signal) for use in the continuity 
equation.33 
 
 
Figure 7. LVOT velocity recording 
(A) Sample volume placement just proximal to zone of pre-valve acceleration (illustration by Mayo Clinic, used with 
permission); (B) Optimal LVOT velocity signal showing a smooth spectral Doppler recording with a narrow velocity 
range at each time point; (C) Illustration showing correct sample volume placement just proximal to inflow of 
stent; (D) Full-screen imaging of stent to ensure positioning of sample volume below the stent. 

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4.3 
Aortic Valve Velocities 
The aortic valve velocity should be interrogated with CW Doppler from a minimum of 2 transducer 
positions (apical and either a parasternal or suprasternal position). The position that provides the 
highest velocity is used for measurements.  A smooth velocity curve with a clear outer edge and 
maximal velocity should be recorded. The maximal velocity is measured at the outer edge of the dark 
signal; fine linear signals at the peak should not be included in measurements. The outer edge of the 
dark “envelope” of the velocity curve is traced to provide both the VTI for the continuity equation and 
the mean gradient (Figure 8).33 
 
Figure 8. Aortic valve velocities 
(A) Aortic valve velocities interrogated from multiple transducer positions (illustration by Mayo Clinic, used with 
permission); (B) CW Doppler of severe aortic stenosis showing tracing of the velocity curve from mean gradient 
and VTI, and measurement of max velocity. 
4.4 
Assessment of Prosthetic Aortic Regurgitation 
An integrated exam approach using color flow, pulsed-wave (PW), and continuous-wave (CW) Doppler is 
used to assess the severity of transvalvular and paravalvular aortic regurgitation (AR).  Color flow 
Doppler imaging should be performed from the parasternal long and short-axis views, and the apical 
long-axis and/or 5-chamber views.  In the short axis view, color imaging should be performed at multiple 
levels (from level of the leaflets to below the skirt and frame to assess paravalvular regurgitation, and at 
the coaptation point of the leaflets for transvalvular (central) regurgitation.37,38  
If AR is seen by color Doppler, a CW Doppler recording of the regurgitant signal should be obtained for 
measurement of pressure half-time and assessment of jet density.  If the degree of AR by color Doppler 
appears more than mild by visual estimate, the velocity in the proximal descending aorta should be 
recorded with PW Doppler. 

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The degree of transvalvular, paravalvular, and total (transvalvular plus paravalvular) AR will be graded as 
none, trace, mild, mild to moderate, moderate, moderate to severe, and severe based on the synthesis 
of the Doppler parameters shown in Table 8.38 The category of “trace” should be used in cases where 
regurgitation is barely detectable by color Doppler.  Regurgitant signals observed to originate within the 
stent will be considered transvalvular, and regurgitant signals observed to originate outside the stent 
will be considered paravalvular. 

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Table 8. Parameters for evaluation of the severity of aortic regurgitation 
 
3-class Grading Scheme 
Trace 
Mild 
Mild 
Moderate 
Moderate 
Severe 
Unifying 5-Class Grading Scheme 
Trace 
Mild 
Mild-to-Moderate 
Moderate 
Moderate-to-severe 
Severe 
Doppler parameters (qualitative or semi-
quantitative) 
 
 
 
 
 
 
 Jet Features 
 
 
 
 
 
 
      Extensive/wide jet origin 
Absent 
Absent 
Absent 
Present 
Present 
Present 
      Multiple jets 
Possible 
Possible 
Often present 
Often present 
Usually present 
Usually present 
      Jet path visible along stent 
Absent 
Absent 
Possible 
Usually present 
Present 
 
      Proximal flow convergence visible 
Absent 
Absent 
Absent 
Possible 
Often present 
Often present 
 Vena contract width (mm) 
<2 
<2 
2-4 
4-5 
5-6 
>6 
 Vena contract area (mm2) 
<5 
5-10 
10-20 
20-30 
30-40 
>40 
 Jet width at origin (% LVOT diameter) 
Narrow (<5) 
Narrow (5-15) 
Intermediate (30-45) 
Large (45-60) 
Large (>60) 
 
 Jet density: CW Doppler 
Incomplete or faint 
Incomplete or faint 
Variable 
Dense 
Dense 
Dense 
 Pressure half-time (ms): CW Doppler 
Slow (>500) 
Slow (>500) 
Slow (>500) 
Variable (200-500) 
Variable (200-500) 
Steep (<200) 
 Diastolic flow reversal in descending aorta 
Absent 
Absent or brief 
early diastolic 
Intermediate 
Holodiastolic (end-
diast. Vel. >20 cm/s) 
Holodiastolic (end-
diast. Vel. >25 cm/s) 
 
 Circumferential extent of PVR (%) 
<10 
<10 
10-20 
20-30 
>30 
>30 
Doppler parameters (quantitative) 
 
 
 
 
 
 
 Regurgitant volume (ml/beat) 
<15 
<15 
15-30 
30-45 
45-60 
>60 
 Regurgitant fraction (%) 
<15 
<15 
5-10 
10-20 
20-30 
>30 
 Effective regurgitant orifice area (mm2) 
<5 
<5 
5-10 
10-20 
20-30 
>30 

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4.5 
Assessment of Mitral Regurgitation 
Color flow Doppler imaging of the left atrium should be performed from the parasternal long-axis view, and 
from the apical 4, 2, and long axis views. 
Mitral regurgitant (MR) jets should be recorded with CW Doppler using a velocity scale that allows 
assessment of the density, shape, duration, and peak velocity of the MR jet. If the severity appears 
moderate or greater by visual assessment, pulmonary vein velocities should be recorded with PW Doppler 
to assess for the presence of systolic flow reversal. Grading of the severity of mitral regurgitation should be 
integrative using the parameters in Table 9.39 
Table 9. Parameters for evaluation of the severity of mitral regurgitation 
Parameter 
Mild 
Moderate 
Severe 
Color flow jet area 
Small, central jet 
(usually <4 cm2 or 
<20% of LA area) 
Variable 
Large central jet 
(usually >10 cm2 or 
>40% of LA area), or variable wall-
impinging jet swirling in the LA 
Jet density (CW) 
Incomplete or faint 
Dense 
Dense 
Jet contour (CW) 
Parabolic 
Usually parabolic 
Early peaking, triangular 
Pulmonary vein flow 
Systolic dominance 
Systolic blunting 
Systolic flow reversal 
4.6 
Assessment of Tricuspid Regurgitation 
Color flow imaging of the right atrium should be performed from the apical 4-chamber view, the 
parasternal long-axis view of the RVOT, and the parasternal short-axis view at the level of the aortic valve. 
Tricuspid regurgitant (TR) jets should be recorded with CW Doppler using a velocity scale that allows 
assessment of the density, shape, duration, and peak velocity of the TR jet. If the severity appears 
moderate or greater by visual assessment, hepatic vein velocities should be recorded with PW Doppler to 
assess for the presence of systolic flow reversal. Grading of the severity of tricuspid regurgitation should be 
integrative using the parameters in Table 10.39  
Table 10. Parameters for evaluation of the severity of tricuspid regurgitation 
Parameter 
Mild 
Moderate 
Severe 
Jet area (cm2) 
<5 
5 – 10 
>10 
VC width (cm) 
Not defined 
Not defined, but <0.7 
≥0.7 
PISA Radius (cm) 
≤0.5 
0.6 – 0.9 
>0.9 
Jet density & contour 
Soft & parabolic 
Dense, variable contour 
Dense, triangular, with early 
peaking 
Hepatic vein flow  
Systolic dominance 
Systolic blunting 
Systolic flow reversal 

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4.7 
Assessment of Left Ventricular Function and Left Atrial Size 
Dimensions of the left ventricle and left atrium should be obtained by either 2-D linear measurements or 
using 2-D guided m-mode from either the parasternal long or short axis views (Figure 9). Left ventricular 
chamber dimensions, septal thickness, and posterior wall thickness are measured using the American 
Society of Echocardiography (ASE) measurement convention38 (blood-tissue interface). In addition, 
standard 2-D views of the left ventricle should be obtained from parasternal and apical transducer positions 
for visual estimation and quantitative assessment of left ventricular ejection fraction using the modified 
Simpson’s rule, and for assessment of regional wall motion. 
 
Figure 9. Left ventricle and left atrium measurements 
Measurements of the left ventricle (A) and left atrium (B) using 2-D guided m-mode. 
 
 
A 
B 

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5.0 
Core Lab Analysis 
Protocol-required echocardiograms will be sent to the Echo Core lab for assessment: the data generated by 
the Echo Core Lab will be the primary data used for analysis and reporting. Received echocardiograms will 
be logged in and analyzed by the Echo Core Lab according to their procedures determined for this study.  
The Echo Core Lab will report the following variables: 
• 
Heart rate 
• 
Left ventricular outflow tract (LVOT) diameter in mid systole 
• 
Max aortic/prosthetic valve velocity (V2) by CW Doppler 
• 
Aortic valve velocity time integral (VTI) by CW Doppler 
• 
Mean gradient across aortic valve (MGV2) by CW Doppler 
• 
LVOT VTI by PW Doppler 
• 
Grade of aortic/prosthetic transvalvular regurgitation  
• 
Grade of aortic/prosthetic paravalvular regurgitation (post-implant only) 
• 
Grade of prosthetic total (transvalvular plus paravalvular) regurgitation (post implant only) 
• 
Grade of mitral regurgitation 
• 
Grade of tricuspid regurgitation 
• 
Max tricuspid regurgitant (TR) jet velocity (if TR is present) 
• 
Left ventricular internal dimension at end diastole 
• 
Left ventricular internal dimension at end systole 
• 
Interventricular septal thickness at end diastole 
• 
Left ventricular posterior wall thickness at end diastole 
• 
Left atrial diameter (anterior-posterior linear dimension) at systole 
• 
Left ventricular ejection fraction by visual estimate 
Qualitative grading of valvular regurgitation will be performed using the criteria described in Sections 4.4 
through 4.6.  For reporting the degree of prosthetic regurgitation, the grading classes may be collapsed 
according to the 3-class grading scheme recommended by the American Society or Echocardiography (ASE)-
European Association of Cardiovascular Imaging Guidelines.39,40 
In addition, the following variables will be derived by the central database from the appropriate 
measurements reported by the Echo Core Lab: 
• 
Peak Pressure Gradient (Peak ∆ P) Across the Aortic Valve in mmHg 
Peak ∆ P = 4 x (V22) 
Where: V2 is the peak velocity across the prosthesis in m/sec 
• 
Aortic Valve Area (AVA) in cm2 
AVA = LVOT diameter in cm2 x 0.785 x (VTIV1/VTIV2) 
Where: VTIV1 is the velocity time integral of the left ventricular outflow tract in cm, and VTIV2 is the velocity 
time integral of the native aortic valve in cm 
• 
Aortic Valve Area Index (AVAI) in cm2/m2 
AVAI = AVA/BSA 

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Where: AVA is the native aortic valve area in cm2, and BSA is the body surface area in m2viii 
• 
Effective Orifice Area (EOA) in cm2 
EOA = LVOT diameter2 x 0.785 x (VTIV1/VTIV2) 
Where: VTIV1 is the velocity time integral of the left ventricular outflow tract in cm, and VTIV2 is the velocity 
time integral of the aortic prosthesis in cm 
• 
Effective Orifice Area Index (EOAI) in cm2/m2 
EOAI = EOA/BSA 
Where: EOA is the effective orifice area in cm2, and BSA is the body surface area in m2 
• 
Doppler Velocity Index (DVI) 
DVI = VTIV1/VTIV2 
Where: VTIV1 is the velocity time integral of the left ventricular outflow tract in cm, and VTIV2 is the time 
velocity integral of the prosthetic aortic valve in cm 
• 
Estimated Right Ventricular Systolic Pressure (RVSP) in mmHg 
RVSP = (4 x MVTR jet2) + 10 
Where: MV TR jet is the max velocity of the tricuspid regurgitant jet, and 10 = the assumed mean right atrial 
pressure in mmHg 
• 
Body Surface Area (BSA) in m2 
BSA = 0.007184 x (height in cm0.725 x weight in kg0.425) 
 
 
 
viii BSA derived from height and weight reported on the site eCRF 

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APPENDIX III: MULTI-SLICE COMPUTED TOMOGRAPHY 
ACQUISTION GUIDELINES 
1.0 
Introduction 
Multi-slice Computed Tomography (Cardiac MSCT) is used to evaluate aortic valve anatomy, determine 
aortic root dimensions for device sizing, and to evaluate peripheral vessel dimensions and anatomy. The 
following sections are intended as guidelines for acquiring the images for assessing anatomical suitability 
for implantation. 
2.0 
General Requirements 
• 
Multi-detector CT scanner (64-slice minimum) with ECG-gating capability. 
• 
ECG-gated contrast enhanced aortic root (slice thickness of ≤ 1.0 mm) 
• 
Temporal resolution should be optimized to reduce motion artifact. 
• 
Spatial resolution should be as high as possible (goal is smallest isotropic voxel size) 
3.0 
ECG-gated Contrast Enhanced Scan of Aortic Root 
Retrospective ECG-gated scans are recommended, which allows for reconstruction in various phases of the 
cardiac cycle and optimal evaluation of anatomic dimensions and valve morphology. Recommended scan 
parameters are listed in Table 11. 
Prospective ECG-gated sequential scans (step-and-shoot) and high-pitch spiral scans with ECG-gating (flash 
spiral) are also acceptable. The following parameters are important to the optimum scan: 
• 
Detector collimation 0.4-0.625 mm. 
• 
Slice thickness ≤ 1.0 mm. 
• 
The recommended coverage area is from superior to the aortic arch to inferior to the cardiac apex. The 
minimum required coverage area is from 50 mm above the aortic annulus to 10 mm below the aortic 
annulus. 
• 
The recommended slice overlap is 0.4 mm (will result in isotropic voxels with a 20 cm field of view). 
3.1 
Post processing 
• 
Retrospective ECG-gated scans 
- 
Verify heart rate ECG triggers are at consistent place in cardiac cycle, edit if necessary. Additional 
editing/removal of arrhythmias may be performed. 
- 
Reconstruct at multiple phases (10 increments of 10%), with ≤ 1.0 mm slice thickness. If the system 
has the capability, also reconstruct a “best systolic” and “best diastolic” phase. 
• 
Prospective ECG-gated scans (including flash spiral) 
- 
Reconstruct with medium soft kernel and slice thickness ≤ 1.0 mm (slice overlap of 0.4 mm 
recommended) 

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Table 11.Recommended scan parameters 
Parameter 
Recommendation 
IV injection with 
iodine contrast 
80-100 (320mg/ml or higher), modify per patient as appropriate 
Injection rate 
4-6 mL/sec 
Bolus tracking, delay 
Delay time calculated using protocol for current scanner (bolus tracking or similar) with 
peak of contrast concentration in the ascending aorta during acquisition. 
ECG-gating 
Retrospective 
Scan direction 
Cranial-caudal 
Scan coverage 
From above the aortic arch to past the cardiac apex 
Detector collimation 
0.4 – 0.625 mm 
Pitch 
0.2–0.43 adapted to the heart rate 
Dose modulation 
Modulation and full current between 30 and 80% of the cardiac cycle 
Slice thickness 
0.8 mm 
Slice overlap 
0.4 mm 
Reconstruction kernel 
Medium Smooth 
Post processing 
Retrospective ECG gating reconstruction algorithm that minimizes motion artifact. 
Reconstruct at multiple phases (10 minimum). Reconstructed slice thickness ≤ 0.8 mm. 
3.2 
Required Aortic Root Measurements 
The following measurements of the aortic root are obtained for assessing anatomical suitability: 
• 
Major aortic annulus (measured at systole if retrospective gating is used) 
• 
Orthogonal minor aortic annulus diameter (measured at systole if retrospective gating is used) 
• 
Annulus perimeter (measured at systole if retrospective gating is used) 
• 
Sinus of Valsalva diameters (measured at diastole) 
• 
Sinus of Valsalva heights (measured at diastole) 
3.2.1  Reformatting of Images41 
• 
Site image cross-hairs on aortic root in all windows where it is visible. Lock cross-hairs so they remain 
orthogonal for all steps. 
• 
In the coronal window, rotate cross-hairs (horizontal line) counter-clockwise to align with virtual basal 
plane, (Figure 10, upper left panel). 
• 
In the sagittal window, the horizontal line is rotated clockwise or counter-clockwise to align with virtual 
basal plane (Figure 10, lower left panel). 
• 
On the newly defined double-oblique axial image, scroll up and down through the aortic root until the 
most caudal attachment points of the three native leaflets come into view (indicated by arrowheads in 
Figure 11). If one of the leaflets comes into view at a more cranial or caudal slice, adjust the coronal or 
sagittal cross-hairs until all three leaflets come into view on the same axial slice. 

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• 
For confirmation of the correct aortic annulus plane, scroll through the double oblique axial images 
starting in the mid sinus and ending at the level of the aortic annulus. The sinuses should appear to be 
relatively the same size at the level of the mid-sinus and the leaflets should all disappear equally at the 
level of the annulus. 
 
Figure 10. Example images in original orientation (axial, coronal, and sagittal) 
Red curved arrow and line indicate adjustment of coronal and sagittal planes to align with aortic basal annulus. 
 
 
Sagittal 
Coronal 
Axial 

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Figure 11. Example images of reformatted oblique coronal, oblique sagittal, double oblique axial, and 3D 
reconstruction 
Example images of reformatted oblique coronal (upper left), oblique sagittal (lower left), double oblique axial (upper 
right), and 3D reconstruction (lower right). Yellow arrowheads indicate most caudal attachment of three leaflets of the 
aortic valve). 
3.2.2  Aortic Annulus Measurements 
• 
Choose the cleanest systolic images for the aortic annulus measurements, either automatically (e.g., 
best systolic) or by manually identifying. Measurement on a diastolic image is also acceptable. 
• 
Aortic annulus measurements should be completed on the properly reformatted double-oblique axial 
image at aortic annulus level, as described in Section 3.2.1, Reformatting of Images. 
• 
Trace the perimeter of the basal annulus (Figure 12, left). Place cross-hairs at site of basal annulus, 
create major diameter through the site, create minor diameter defined as perpendicular to major and 
through site (Figure 12, right). 
Oblique 
Coronal 
Oblique 
Sagittal 
Double-oblique axial 

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Figure 12. Aortic annulus measurements 
Example of perimeter measurement (left) and major and minor diameter measurements (right). 
3.2.3 Sinus of Valsalva Measurements 
Choose the best diastolic images for measurement of sinus of Valsalva diameters and heights from images 
using the same reformatting technique as described in Section 3.2.1. 
Sinus of Valsalva Diameters 
• 
Select the double oblique axial image where the widest portion of the three sinuses is visible. 
• 
For tricuspid aortic valves, measure a diameter from each commissure through the site of the root to 
the opposite sinus. Complete for all three sinuses (Figure 13, left).  For Sievers Type 1 bicuspid aortic 
valves, measure the commissure to opposing sinus using a single line measurement tool; complete for 
all three sinuses (Figure 13, right). 

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Figure 13. Examples of Sinus of Valsalva diameters 
Examples of tricuspid valves (left) and Sievers Type I bicuspid valves (right). 
Sinus of Valsalva Heights 
• 
The sinotubular junction is typically not co-planar with the aortic annulus. Therefore, a sinus of Valsalva 
height must be measured for each of the three sinuses. This height is defined as the distance between 
the aortic annular plane and the tallest point in the sinus. 
• 
Choose the double oblique axial image so that it is located at the level of the aortic annulus. The 
reformatting line representing the double oblique axial image should now be visible in the oblique 
coronal and oblique sagittal images at the level of the aortic annulus.  
• 
For the left coronary and non-coronary heights, use the oblique coronal image. For the right coronary 
height, use the oblique sagittal image. 
• 
To complete the measurement, scroll through the oblique coronal or sagittal image (depending on 
which sinus you are measuring) and locate the heights location of the sinotubular junction. On that 
image, measure the distance along the path of the aortic root from the aortic annular plane, marked by 
the reformatting line, to the sinotubular junction (Figure 14). 
 

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Figure 14. Examples of Sinus of Valsalva heights 
(A) left coronary; (B) non-coronary; (C) right coronary 
 
4.0 
Anatomic Suitability and Valve Size Selection 
TAV Size 
Aortic Annulus 
Sinus of Valsalva 
Perimeter 
(mm) 
Mean Diameter 
(mm) 
Mean Diameter 
(mm) 
Mean Height 
(mm) 
23 mm 
56.5 – 62.8 
18 – 20 
≥ 25 
≥ 15 
26 mm 
62.8 – 72.3 
20 – 23 
≥ 27 
≥ 15 
29 mm 
72.3 – 81.7 
23 – 26 
≥ 29 
≥ 15 
 
 
 

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APPENDIX IV: STS CALCULATOR AND RISK FACTORS 
1.0 
STS Calculator 
STS-PROM scores are to be calculated using the current Risk Model and Variables – STS Adult Cardiac 
Surgery Database at http://riskcalc.sts.org/stswebriskcalc/#/calculate. The risk model and variable 
definitions are provided within the database42.  
2.0 
Other Factors Not Captured by Traditional Risk Score1 
Co-morbidity 
Definition/Criteria 
Porcelain aorta or 
severely 
atherosclerotic aorta 
Heavy circumferential calcification or severe atheromatous plaques of the entire 
ascending aorta extending to the arch such that aortic cross-clamping is not feasible. 
Frailty 
Slowness, weakness, exhaustion, wasting and malnutrition, poor endurance and inactivity, 
loss of independence 
Criteria:  
• 
5-meter walking time 
• 
Grip strength*  
• 
BMI <20 kg/m2 and/or weight loss 5 kg/yr  
• 
Serum albumin <3.5 g/dL  
• 
Cognitive impairment or dementia  
Sever liver 
disease/cirrhosis 
Any of the following: 
• 
Child-Pugh class C  
• 
MELD score ≥10  
• 
Portal-caval, spleno-renal, or transjugular intrahepatic portal shunt  
• 
Biopsy proven cirrhosis with portal hypertension or hepatocellular dysfunction  
Hostile chest 
Any of the following or other reasons that make redo operation through sternotomy or 
right anterior thoracotomy prohibitively hazardous:  
• 
Abnormal chest wall anatomy due to severe kyphoscoliosis or other skeletal 
abnormalities (including thoracoplasty, Potts’ disease)  
• 
Complications from prior surgery  
• 
Evidence of severe radiation damage (e.g., skin burns, bone destruction, muscle loss, 
lung fibrosis or esophageal stricture)  
• 
History of multiple recurrent pleural effusions causing internal adhesions  
IMA or other critical 
conduit(s) crossing 
midline and/or 
adherent to posterior 
table of sternum  
 
A patent IMA graft that is adherent to the sternum such that injuring it during re-
operation is likely. A patient may be considered extreme risk if any of the following are 
present:  
• 
The conduit(s) are radiographically indistinguishable from the posterior table of the 
sternum.  
• 
The conduit(s) are radiographically distinguishable from the posterior table of the 
sternum but lie within 2-3 mm of the posterior table. 
Severe pulmonary 
hypertension  
Primary or secondary pulmonary hypertension with PA systolic pressures greater than 2/3 
of systemic pressure  

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Co-morbidity 
Definition/Criteria 
Severe right 
ventricular 
dysfunction  
Criteria as defined by the guidelines (e.g., TAPSE <15mm, RV end-systolic area >20 cm2, 
etc.) 
 
 
 

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APPENDIX V: DEFINITIONS: SAFETY ENDPOINTS AND EFFICACY 
EVENTS 
Definitions of adverse events to be evaluated as clinical safety endpoints, other TAVI-related complications, 
and efficacy events are provided in Sections 1.0, 2.0, and 3.0, respectively. Site investigators will classify the 
causal relationships between the event and the TAV, the delivery catheter system, and the TAVR implant 
procedure according to the definitions provided on Section 4.0. 
1.0 
Safety Endpoint Definitions 
Mortality 
Cardiovascular 
mortality 
Any of the following criteria: 
1) Death due to proximate cardiac cause (e.g., myocardial infarction, cardiac tamponade, 
worsening heart failure) 
2) Death caused by non-coronary vascular conditions such as neurological events, 
pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular 
disease 
3) All procedure-related deaths, including those related to a complication of the procedure 
or treatment for a complication of the procedure 
4) All valve-related deaths including structural or nonstructural valve dysfunction or other 
valve-related adverse events 
5) Sudden or unwitnessed death 
6) Death of unknown cause 
Non-cardiovascular 
mortality 
Any death in which the primary cause of death is clearly related to another condition (e.g., 
trauma, cancer, suicide). 
 
Myocardial Infarction 
Periprocedural MI 
(≤72 h after the 
index procedure) 
New ischemic symptoms (e.g., chest pain or shortness of breath), or new ischemic signs 
(e.g., ventricular arrhythmias, new or worsening heart failure, new ST-segment changes, 
hemodynamic instability, new pathological Q-waves in at least 2 contiguous leads, imaging 
evidence of new loss of viable myocardium or new wall motion abnormality)  
AND 
Elevated cardiac biomarkers (preferable CK-MB) within 72 h after the index procedure, 
consisting of at least 1 sample post procedure with a peak value exceeding 15x as the upper 
reference limit for troponin or 5x for CK-MB. If cardiac biomarkers are increased at baseline 
(>99th percentile), a further increase in at least 50% post procedure is required AND the 
peak value must exceed the previously stated limit. 
Spontaneous MI 
(>72 h after the 
index procedure) 
Any of the following criteria: 
1) Detection of rise and/or fall of cardiac biomarkers (preferably troponin) with at least 1 
value above the 99th percentile URL, together with the evidence of myocardial ischemia 
with at least 1 of the following: 
• 
Symptoms of ischemia 
• 
ECG changes indicative of new ischemia [new ST-T changes or new left bundle 
branch block (LBBB)] 

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Myocardial Infarction 
• 
New pathological Q-waves in at least 2 contiguous leads 
• 
Imaging evidence of a new loss of viable myocardium or new wall motion 
abnormality 
2) Sudden, unexpected cardiac death, involving cardiac arrest, often with symptoms 
suggestive of myocardial ischemia, and accompanied by presumably new ST elevation, 
or new LBBB, and/or evidence of fresh thrombus by coronary angiography and/or at 
autopsy, but death occurring before blood samples could be obtained, or at a time 
before the appearance of cardiac biomarkers in the blood. 
3) Pathological findings of an acute myocardial infarction  
 
Stroke and TIA 
Diagnostic criteria 
1) Acute episode of a focal or global neurological deficit with at least 1 of the following:  
• 
change in the level of consciousness 
• 
hemiplegia, hemiparesis 
• 
numbness or sensory loss affecting 1 side of the body 
• 
dysphasia or aphasia 
• 
hemianopia 
• 
amaurosis fugax 
• 
other neurological signs or symptoms consistent with stroke 
Stroke: duration of a focal or global neurological deficit ≥24 h; OR <24 h if available neuroimaging documents a 
new hemorrhage or infarct; OR the neurological deficit results in death 
TIA: duration of a focal or global neurological deficit <24 h, any variable neuroimaging does not demonstrate a 
new hemorrhage or infarct 
2) No other readily identifiable non-stroke cause for the clinical presentation (e.g., brain tumor, trauma, infection, 
hypoglycemia, peripheral lesion, pharmacological influences), to be determined by or in conjunction with the 
designated neurologist 
3) Confirmation of the diagnosis by at least 1 of the following: 
• 
Neurologist or neurosurgical specialist 
• 
Neuroimaging procedure (CT scan or brain MRI), but stroke may be diagnosed on clinical grounds alone 
Stroke Definitions 
Disabling stroke: an mRS score of 2 or more at 90 days and an increase in at least 1 mRS category from an 
individual’s pre-stroke baseline 
Non-disabling stroke: an mRS score of <2 at 90 days or one that does not result in an increase in at least 1 mRS 
category from an individual’s pre-stroke baseline 
Stroke Classifications 

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Stroke and TIA 
Ischemic: an acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of the central 
nervous system tissue 
Hemorrhagic: an acute episode of focal or global cerebral or spinal dysfunction caused by intraparenchymal, 
intraventricular, or subarachnoid hemorrhage 
Undetermined: insufficient information to allow categorization as ischemic or hemorrhagic 
 
Bleeding Complications 
Life-threatening or 
disabling bleeding 
1) Fatal bleeding (BARC type 5) OR 
2) Bleeding in a critical organ, such as intracranial, intraspinal, 
intraocular, or pericardial necessitating pericardiocentesis, or intramuscular with 
compartment syndrome (BARC type 3b and 3c) OR 
3) Bleeding causing hypovolemic shock or severe hypotension requiring vasopressors or 
surgery (BARC type 3b) OR 
4) Overt source of bleeding with drop in hemoglobin ≥5 g/dL or whole blood or packed 
red blood cells (RBCs) transfusion ≥4 units* 
(BARC type 3b) 
Major bleeding 
(BARC type 3a) 
1) Overt bleeding either associated with a drop in the hemoglobin level of at least 3.0 
g/dL or requiring transfusion of 2 or 3 units of whole blood/RBC, or causing 
hospitalization or permanent injury, or requiring surgery AND 
2) Does not meet criteria of life-threatening or disabling bleeding 
Minor bleeding 
(BARC type 2 or 3a, 
depending on the 
severity) 
Any bleeding worthy of clinical mention (e.g., access site hematoma) that does not qualify 
as life-threatening, disabling, or major 
*Given one unit of packed RBC typically will raise hemoglobin concentration by 1 g/dL, an estimated decrease in 
hemoglobin will be calculated; BARC: Bleeding Academic Research Consortium29; RBC: red blood cell  
Note: With respect to blood transfusions, it is critical to acknowledge that a bleeding complication has to be the result of overt 
bleeding and cannot be adjudicated based on blood transfusions alone. 
 
Acute Kidney Injury (up to 7 days post procedure) 
Stage 1 
1) Increase in serum creatinine to 150%-199% (1.5-1.99 x increase compared with 
baseline) OR increase of ≥0.3 mg/dL (≥26.4 mmol/L) OR 
2) Urine output <0.5 mL/kg/h for >6 but <12 h 
Stage 2 
1) Increase in serum creatinine to 200%-299% (2.0%-2.99% increase compared with 
baseline) OR 
2) Urine output <0.5 mL/kg/h for >12 but <24 h 

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Acute Kidney Injury (up to 7 days post procedure) 
Stage 3 
1) Increase in serum creatinine to ≥300% (>3 x increase compared with baseline) OR 
serum creatinine of ≥4.0 mg/dL (≥354 mmol/L) with an acute increase of at least 0.5 
mg/dL (44 mmol/L) OR 
2) Urine output <0.3 ml/kg/h for ≥24 h OR 
3) Anuria for ≥12 h 
 
Vascular Access Site and Access Related Complications 
Major vascular 
complication 
1) Any aortic dissection, aortic rupture, annulus rupture, left ventricle perforation, or 
new apical aneurysm/pseudoaneurysm OR 
2) Access site or access-related vascular injury (dissection, stenosis, perforation, rupture, 
arterio-venous fistula, pseudoaneurysm, hematoma, irreversible nerve injury, 
compartment syndrome, percutaneous closure device failure) leading to death, life-
threatening or major bleeding, visceral ischemia, or neurological impairment OR 
3) Distal embolization (noncerebral) from a vascular source requiring surgery or resulting 
in amputation or irreversible end-organ damage OR 
4) The use of unplanned endovascular or surgical intervention associated with death, 
major bleeding, visceral ischemia or neurological impairment OR 
5) Any new ipsilateral lower extremity ischemia documented by patient symptoms, 
physical exam, and/or decreased or absent blood flow on lower extremity angiogram 
OR 
6) Surgery for access site-related nerve injury OR 
7) Permanent access site-related nerve injury 
Minor vascular 
complication 
1) Access site or access-related vascular injury (dissection, stenosis, perforation, rupture, 
arterio-venous fistula, pseudoaneuysms, hematomas, percutaneous closure device 
failure) not leading to death, life-threatening or major bleeding*, visceral ischemia, or 
neurological impairment OR 
2) Distal embolization treated with embolectomy and/or thrombectomy and not 
resulting in amputation or irreversible end-organ damage OR 
3) Any unplanned endovascular stenting or unplanned surgical intervention not meeting 
the criteria for a major vascular complication OR 
4) Vascular repair or the need for vascular repair (via surgery, ultrasound-guided 
compression, transcatheter embolization, or stent-graft) 
Percutaneous closure 
device failure 
Failure of a closure device to achieve hemostasis at the arteriotomy site leading to 
alternative treatment (other than manual compression or adjunctive endovascular 
ballooning) 
*Refer to VARC bleeding definitions1 
 
 

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VALVE DYSFUNCTION REQUIRING REPEAT PROCEDURE 
Any valve dysfunction that requires repeat procedure (e.g., balloon valvuloplasty, TAVI, or surgical AVR) 
Note: Repeat procedures are reported on the appropriate eCRF (Surgical Intervention or Catheter Reintervention) 
2.0 
Other TAVI Related Complications 
Complication 
Definition 
Conversion to open surgery 
Conversion to open sternotomy during the TAVI procedure secondary to any 
procedure-related complications 
Unplanned use of 
cardiopulmonary bypass 
Unplanned use of CPB for hemodynamic support at any time during the TAVI 
procedure 
Coronary artery obstruction 
Angiographic or echocardiographic evidence of a new, partial or complete, 
obstruction of a coronary ostium, either by the CoreValve™ Evolut™ PRO 
prosthesis itself, the native leaflets, calcifications, or dissection, occurring 
during or after the TAVI procedure. 
Ventricular septal perforation 
Angiographic or echocardiographic evidence of a new septal perforation 
during or after the TAVI procedure 
Mitral valve apparatus damage or 
dysfunction 
Angiographic or echocardiographic evidence of new damage (chordae, 
papillary muscle, or leaflet) to the mitral valve apparatus or dysfunction (e.g., 
restrictions due to the CoreValve™ Evolut™ PRO) of the mitral valve during or 
after the TAVI procedure 
Cardiac tamponade 
Evidence of new pericardial effusion associated with hemodynamic instability 
and clearly related to the TAVI procedure 
Prosthetic valve thrombosis 
Any thrombus attached to or near an implanted valve that occludes part of 
the blood flow path, interferes with valve function, or is sufficiently large to 
warrant treatment. 
*Valve-associated thrombus identified at autopsy in a patient whose cause of 
death was not valve related should not be reported as valve thrombosis. 
Valve migration 
After initial correct positioning, any observed movement (upward or 
downward) of the Evolut PRO within the aortic annulus from its initial 
position, with or without consequences. 
Valve embolization 
The Evolut PRO moves during or after deployment such that it loses contact 
within the aortic annulus  
Note: Valve embolizations are not applicable to valve that move during the 
procedure but are able to be recaptured and repositioned. 
Ectopic valve deployment 
Permanent deployment of the Evolut PRO in a location other than the aortic 
root 
TAV in TAV deployment 
Additional valve prosthesis is implanted within a previously implanted 
CoreValve™ Evolut™ PRO because of sub-optimal device position and/or 
function, during or after the index procedure. 
Hemolysis 
Red cell destruction as evidenced by plasma free hemoglobin >50 mg/dl 
Minor hemolysis: No intervention required 
Major hemolysis: Requires intervention (e.g., iron supplements, transfusion, 
invasive intervention). 

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Complication 
Definition 
Frame fracture 
Visual evidence on radiography or at explant of loss of contact between 
elements (cells) of the stent. 
Minor frame fracture: Does not require intervention or is not associated with 
prosthetic valve dysfunction. 
Major frame fracture: Intervention required (e.g., reoperation, catheter re-
intervention) or is associated with prosthetic valve dysfunction 
Valve Thrombosis (Sub-Clinical) 
Any thrombus not caused by infection attached to or near the trial valve 
that occludes part of the blood flow path or interferes with valve function, 
without evident clinical sequelae, causing a hemodynamic impediment 
meeting the following criteria: 
• 
Increase in aortic regurgitation to moderate to severe. 
An increase by more than 50% of discharge mean aortic valve gradient (with 
the post discharge mean gradient being ≥ 20 mmHg) or a decrease in the 
Doppler Velocity Index (DVI) by more than 50% 
Leaflet Motion Abnormality (With 
Treatment) 
Possible leaflet motion abnormality identified by any imaging modality with 
medical therapy (e.g., anticoagulation therapy, fibrinolytic therapy or valve- 
related medical intervention) initiated and without significant negative 
change in valve function (i.e. increasing obstruction or central regurgitation). 
Leaflet Motion Abnormality 
(Without Treatment) 
Possible leaflet motion abnormality identified by any imaging modality 
without medical therapy (e.g., anticoagulation therapy, fibrinolytic therapy or 
valve-related medical intervention) initiated but without significant negative 
change in valve function (i.e. increasing obstruction or central regurgitation). 
TAVR Conversion to Other 
Percutaneous Procedure 
Any conversion of the intended TAVR procedure, prior to closure to other 
percutaneous intervention due to technical challenges, technical 
contraindications to the intended procedure identified intra-procedurally or 
complications. 
Aborted Procedure 
Termination of the procedure prior to implantation of the valve due to 
identification of a technical contraindication, intraprocedural complications of 
a concomitant procedure prior to valve implantation or radiation dosage. 
Reintervention – Surgical or 
Percutaneous 
Any surgical or percutaneous interventional catheter procedure that repairs, 
otherwise alters or adjusts, or replaces a previously implanted valve. In 
addition to surgical reoperations, balloon dilatation, interventional 
manipulation, repositioning, or retrieval, and other catheter-based 
interventions for valve-related complications are also considered 
reinterventions. Reintervention is further subdivided into surgical and 
percutaneous. 
 
 
 
PROSTHETIC VALVE ENDOCARDITIS 
Any of the following: 
1) Fulfillment of the following Duke criteria43 for definite endocarditis: 

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PROSTHETIC VALVE ENDOCARDITIS 
• 
Histologic and/or microbiologic evidence of infection at surgery or autopsy, or 
• 
2 major criteria, or 
• 
1 major criteria or 3 minor criteria, or  
• 
5 minor criteria 
Major and minor criteria are as follows: 
Major Criteria: 
• 
Blood cultures positive for Infective Endocarditis (IE) 
o 
Typical microorganisms consistent with IE isolated from two separate blood cultures, as noted below 
• 
Viridans streptococci, Streptococcus bovis, Staphylcoccus aureus, or HACEK group 
• 
Community-acquired enterococci in the presence of a primary focus 
o 
Microorganisms consistent with IE isolated from persistently positive blood cultures defined as: 
• 
At least two positive cultures or blood samples obtained >12 hours apart, or 
• 
All of three, or a majority of four or more separate cultures of blood, the first and last 
sample obtained > one hour apart 
o 
Single blood culture positive for Coxiella burnetti or an antiphase I IG antibody titer >1:800 
• 
Evidence of endocardial involvement 
o 
Positive results of echocardiography for IE defined as: 
• 
Oscillating intracardiac mass on a valve or supporting structures in the path of regurgitant 
jets or on implanted material in the absence of an anatomic explantation, or 
• 
Abscess, or 
• 
New partial dehiscence of a valvular prosthesis 
o 
New valvular regurgitation (worsening or changing or pre-existing murmur not sufficient) 
Minor Criteria: 
 
• 
Predisposition: predisposing heart condition or intravenous drug use 
• 
Fever: temperature >38◦C 
• 
Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial 
hemorrhage, conjunctival hemorrhages, and Janeway’s lesions 
• 
Immunological phenomena: glomerulonephritis, Osler’s nodes, Roth’s spots, and rheumatoid factor 
• 
Microbiological evidence: positive blood culture but does not meet a major criterion (as noted above) 
or serological evidence of active infection with organism consistent with infectious endocarditis. 
• 
Echocardiographic findings: consistent with IE but do not meet a major criterion as noted above 
If only 1 major and 1-2 minor criteria are fulfilled, or if only 3-4 minor criteria are fulfilled, the event will be 
coded as “possible endocarditis” 
2) Evidence of abscess, paravalvular leak, pus, or vegetation confirmed as secondary to infection by histological or 
bacteriological studies during a re-operation 
3) Findings of abscess, pus, or vegetation involving the CoreValve™ Evolut™ PRO at autopsy 
 
3.0 
Efficacy Event Definitions 
PROSTHETIC VALVE DYSFUNCTION 
Stenosis: moderate/severe 
 
Any of the following  
1) 
Peak aortic velocity >4 m/s OR mean aortic gradient >40 
mmHg, AND EOA <0.8 cm2. 

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PROSTHETIC VALVE DYSFUNCTION 
2) 
Peak aortic velocity >4 m/s OR mean aortic gradient >40 
mmHg, AND EOA ≥0.8 cm2, and DVI <0.25, 
3) 
Peak aortic velocity ≤4 m/s and mean aortic gradient ≤ 40 
mmHg, AND EOA <0.8 cm2, and DVI <0.25 
Paravalvular regurgitation: moderate 
Moderate paravalvular regurgitation (per echo criteria in CIP, Table 8) 
Paravalvular regurgitation: severe 
Severe paravalvular regurgitation (per echo criteria in CIP, Table 8) 
Transvalvular regurgitation: moderate 
Moderate transvalvular regurgitation (per echo criteria in CIP, Table 8) 
Transvalvular regurgitation: severe 
Moderate or severe transvalvular regurgitation (per echo criteria in CIP, 
Table 8) 
Total regurgitation: moderate 
Moderate total regurgitation (per echo criteria in CIP, Table 8) 
Total regurgitation: severe 
Severe total regurgitation (per echo in CIP, Table 8) 
Notes: 
 
1. DVI = Doppler Velocity Index (LVOT VTI/valve VTI) 
2. For subjects with BSA <1.6 m2, the EOA criteria for significant (moderate or severe) stenosis is <0.6 cm2 
3. For subjects LVOT diameter >2.5 cm, the DVI criteria for significant (moderate or severe) stenosis is 0.2 
4. Reporting of prosthetic valve dysfunction will be based on core lab values (if available). 
5. Prosthetic valve dysfunction events are not reported as adverse events, unless the dysfunction is accompanied with clinical 
sequelae at the time of event detection, and the clinical sequelae are chronologically and physiologically associated with the 
dysfunction. However, prosthetic dysfunctions that are associated with adverse events, and that meet the definition of a 
serious adverse event, should be reported as such. 

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4.0 
Classification of Causal Relationships 
The following definitions are intended as guidelines for classifying causal relationships between the 
event and the TAV, the delivery catheter system, and the TAVR implant procedure. Timeframe for 
assessing implant procedure relationships begins when the subject is being prepared for the TAVR 
implant (or re-implant) procedure. 
Causal relationships between event and the TAV  
Not related to the 
TAV 
The relationship to TAV can be excluded when: 
• 
the event is not a known side effect of the TAV product category the device belongs 
to or of similar devices; 
• 
The event has no temporal relationship with the TAV  
• 
The event does not follow a known response pattern to the TAV is biologically 
implausible;  
• 
The event involves a body-site or an organ not expected 
In order to establish non-relatedness, not all the criteria listed above might be met at the 
same time. 
Unlikely to be related 
to the TAV 
The relationship with the TAV seems not relevant and/or the event can be reasonably 
explained by another cause, but additional information may be obtained. 
Possibly related to the 
TAV 
The relationship with the TAV is weak but cannot be ruled out completely. Alternative 
causes are also possible (e.g., an underlying or concurrent illness/ clinical condition or/and 
an effect of another device, drug or treatment). Cases where relatedness cannot be 
assessed or no information has been obtained should also be classified as possible. 
Probably related to 
the TAV 
The relationship with TAV seems relevant and/or the event cannot reasonably be 
explained by another cause, but additional information may be obtained. 
Causal relationship 
“Related” to the TAV 
The event is associated with the TAV beyond reasonable doubt when:  
• 
the event is a known side effect of the TAV product category the device 
belongs to or of similar devices; 
• 
the event has a temporal relationship with investigational device 
use/application or procedures; 
• 
the event involves a body-site or organ that  
o the TAV or surgical valve is applied to;  
o the TAV of surgical valve has an effect on; 
• 
the event follows a known response pattern to the TAV; 
• 
other possible causes (e.g., an underlying or concurrent illness/clinical 
condition or an effect of another device, drug, or treatment) have been 
adequately ruled out 
• 
harm to the subject is due to error in use 
In order to establish relatedness, not all the criteria listed above might be met at the same 
time. 

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Causal relationships between event and the TAVR delivery system 
Not related to the TAVR 
delivery system 
The relationship with the TAVR delivery system can be excluded when:  
• 
the event is not a known side effect of the TAVR delivery system product category 
the device belongs to or of similar devices; 
• 
The event has no temporal relationship with the use of the TAVR delivery system 
• 
The event does not follow a known response pattern to the TAVR delivery system 
and is biologically implausible;  
• 
The event involves a body-site or an organ not expected 
In order to establish non-relatedness, not all the criteria listed above might be met at 
the same time 
Unlikely to be related to 
the TAVR delivery system 
The relationship with the TAVR delivery system seems not relevant and/or the event 
can be reasonably explained by another cause, but additional information may be 
obtained. 
Possibly related to the 
TAVR delivery system 
The relationship with the TAVR delivery system is weak but cannot be ruled out 
completely. Alternative causes are also possible (e.g., an underlying or concurrent 
illness/ clinical condition or/and an effect of another device, drug or treatment). Cases 
were relatedness cannot be assessed or no information has been obtained should also 
be classified as possible. 
Probably related to the 
TAVR delivery system 
The relationship with the TAVR delivery system seems relevant and/or the event 
cannot reasonably be explained by another cause, but additional information may be 
obtained. 
Causal relationship 
“Related” to the TAVR 
delivery system 
The event is associated with the TAVR delivery system reasonable beyond doubt 
when: 
• 
the event is a known side effect of the product category the device 
belongs to or of similar devices; 
• 
the event has a temporal relationship with the TAVR delivery system 
use/application; 
• 
the event involves a body-site or organ that  
o the TAVR delivery system is applied to;  
o the TAVR delivery system has an effect on; 
• 
the event follows a known response pattern to the TAVR delivery system; 
• 
other possible causes (e.g., an underlying or concurrent illness/clinical 
condition or an effect of another device, drug, or treatment) have been 
adequately ruled out 
• 
harm to the subject is due to error in use 
In order to establish relatedness, not all the criteria listed above might be met at the 
same time. 
 
 

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Causal relationships between event and the TAVR implant procedure 
Not related to the TAVR 
implant procedure 
The relationship with the TAVR implant procedure can be excluded when:  
• 
the event is not a known side effect of the TAVR implant procedure; 
• 
The event has no temporal relationship with the TAVR implant relationship 
• 
The event does not follow a known response pattern to the TAVR implant 
procedure and is biologically implausible;  
• 
The event involves a body-site or an organ not expected 
In order to establish non-relatedness, not all the criteria listed above might be met at 
the same time. 
Unlikely to be related to 
the TAVR implant 
procedure 
The relationship with the TAVR implant procedure seems not relevant and/or the 
event can be reasonably explained by another cause, but additional information may 
be obtained. 
Possibly related to the 
TAVR implant procedure 
The relationship with the TAVR implant procedure is weak but cannot be ruled out 
completely. Alternative causes are also possible (e.g., an underlying or concurrent 
illness/ clinical condition or/and an effect of another device, drug or treatment). Cases 
were relatedness cannot be assessed or no information has been obtained should also 
be classified as possible. 
Probably related to the 
TAVR implant procedure 
The relationship with TAVR implant procedure seems relevant and/or the event 
cannot reasonably be explained by another cause, but additional information may be 
obtained. 
Causal relationship 
“Related” to the TAVR 
delivery system 
The event is associated with the TAVR implant procedure beyond reasonable doubt 
when:  
• 
the event is a known side effect of the TAVR implant procedure; 
• 
the event has a temporal relationship with the TAVR implant procedure; 
• 
the event involves a body-site or organ that  
o the TAVR is applied to;  
o the TAVR implant procedure has an effect on; 
• 
the event follows a known response pattern to the TAVR implant 
procedure; 
• 
other possible causes (e.g., an underlying or concurrent illness/clinical 
condition or an effect of another device, drug, or treatment) have been 
adequately ruled out 
• 
harm to the subject is due to error in use 
In order to establish relatedness, not all the criteria listed above might be met at the 
same time. 
Note: Procedure related events refer to the procedure related to the initial application of the investigational medical device only and therefore 
not to any other procedures or treatments applied later throughout the clinical investigation, for instance to treat (serious) adverse events. 
 
 

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APPENDIX VI: STUDY CONTACTS 
 
Sponsor: 
Medtronic CoreValve LLC  
 
 
Local Sponsor (Project & 
Site Management): 
Medtronic (Shanghai) Management Co., Ltd 
 
Monitoring & Site 
Management 
 Medtronic Core Clinical Solutions 
Clinical Events 
Committee: 
Baim Institute for Clinical Research 
 
 
 
 
  
Echocardiography Core 
Laboratory: 
Mayo Foundation 
  
  
 
The detailed contact list will be kept separate from the CIP and provided to the investigators. Medtronic 
will maintain an updated list. For specific contact information of the core members (e.g. Medical expert) 
refer to the detailed list. 
 
For the relevant qualification documents of Medtronic refer to the EC review document package. 
 
 

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APPENDIX VII: SAMPLE INFORMED CONSENT FORM 
 
Sample Informed Consent Form will be provided in a separate cover. 
 
 
 

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28. Version History 
 
Version 
Summary of Changes 
Author(s)/Title 
1.0 
• 
Not Applicable, New Document 
 
2.0 
• 
Sections 6.0 and 7.2.1: Revised to correct 
outer wrap description from 2.0 to 1.5 
cells.  Rationale: align with engineering 
documents and IB.  
• 
Section 7.2.3 Figure 2: Corrected loading 
system name from Evolut PRO to EnVeo 
PRO 
• 
Section 16.6: Removed reference to “AE 
code list’ and added ‘The AE code list will 
be provided under a separate cover.‘ 
• 
Section 16.7.3, Table 5: Removed ‘with 
SADE potential’ as the Investigator should 
submit all AEs and DDs to Medtronic 
• 
Section 21.1: Added ‘The cost of the 
medical check-ups which are required by 
the study will be reimbursed as well.’ for 
consistency with the Patient Informed 
Consent Form 
• 
Minor formatting changes throughout 
 
3.0 
• 
Cover and Content: Updated lead site 
name, lead site investigator, the co-
investigator  
• 
Section 5.3:  deleted “vendor”.  
• 
Section 9.1.1.4: Other Outcome Measures 
• 
Added New York Heart Association (NYHA) 
functional classification at 30days. 
• 
Section 9.2.7.5 and 9.2.7.6: Revised the 
paragraph for Device Malfunction or 
Explant. 
• 
Section 9 (including fig.4): Added the point 
of screening and revised the point of 
enrollment and the related sections. 
• 
Content: Revised “AE” to “Ae”, “Ec” to 
“EC”. 
 
 

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• 
Fig1 and Appendix VI: STUDY CONTACTS: 
Delete Pathology Core Laboratory; Update 
Monitoring & Site Management. 
• 
Appendix V: revised “Moderate 
paravalvular regurgitation” to “Moderate 
transvalvular regurgitation”. 
4.0 
• 
Investigational Product Registration 
Approval Status Update 
• 
Device Success Analysis Cohort Correction 
• 
Supplemental Definitions for CIP Appendix 
V, Section 2.0- Other TAVI-related 
Complications 
• 
Updated all relevant sections to align with 
requirements of new NMPA GCP for 
Medical Devices 
• 
Fig1 and Appendix VI: STUDY CONTACTS: 
Delete Wuxi Clinical Development Services 
and replace with Medtronic Core Clinical 
Solutions. 
• 
Miscellaneous administrative 
updates/corrections throughout 
 
 
 
 

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29. References 
 
 
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after transcatheter aortic valve implantation. Journal of the American College of Cardiology. 
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21 Data on file at Medtronic: Evolut R ER/HR CSR (10181318DOC); Continued Follow-up of the CoreValve 
Evolut R US Cohort Post Approval Clinical Report (January 3, 2018). 
22 Data on file at Medtronic (10791732DOC). 
 

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