Optimize PRO Transcatheter Aortic Valve Replacement Post Market Study
Conditions: Symptomatic Aortic Stenosis
Sponsor: Medtronic Cardiovascular

 
Optimize PRO Study 
 
NCT: 04091048 
 
Study Protocol/Document Date: 04May2021 

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Clinical Investigation Plan 
Clinical Investigation Plan/Study Title  Optimize PRO TAVR Post Market Study  
Study Product Name Medtronic Evolut™ PRO System and Medtronic Evolut™ 
PRO+ System 
Sponsor/Local Sponsor Global Sponsor (funding source): 
Medtronic, Inc. 
Coronary and Structural Heart Clinical  
 
 
 
  
 
Local Sponsors:  
 
 
 
 
Medtronic of Canada ULC 
  
  
 
(EU Legal Representative) 
Medtronic Bakken Research Center BV 
  
 
Medtronic Australia Pty. Ltd 
 
 
 
Medtronic New Zealand Limited 
 
 
Document Version 6.0, 04 May 2021 
Co-Principal Investigators Dr. Kendra Grubb 
Emory University Hospital 
 
 
 
Dr. Steven Yakubov 

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Riverside Methodist Hospital / Ohio Health Research 
Institute 
 
 
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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1. Investigator Statement 
Study product Name 
Medtronic Evolut™ PRO and Medtronic Evolut™ PRO+ 
Sponsor 
Medtronic Structural Heart Clinical  
Version Number/Date  
6.0, 04 May 2021 
I have read the protocol, including all appendices, and I agree that it contains all necessary details for me 
and my staff to conduct this study as described. I will conduct this study as outlined herein and will make 
a reasonable effort to complete the study within the time designated. 
I agree to comply with local and internal institutional requirements including the protocol, GCP, and 
ethical principles that have their origin in the Declaration of Helsinki.   
I agree to ensure that the confidential information contained in this document will not be used for any 
purpose other than the evaluation and conduct of the clinical study without the prior written consent of 
Medtronic. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Medtronic. I will discuss this material with them to ensure that they are fully 
informed about the products and the study. 
Investigator’s Signature: 
 
Investigator’s Name: 
 
Institution: 
 
Date:  
 
 
 

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Table of Contents  
 
1. 
Investigator Statement.................................................................................................................... 3 
Table of Contents ................................................................................................................................... 4 
2. 
Glossary .......................................................................................................................................... 9 
3. 
Synopsis ....................................................................................................................................... 11 
4. 
Introduction.................................................................................................................................. 14 
4.1. Background and Rationale ................................................................................................................... 14 
4.2. Purpose ................................................................................................................................................ 14 
5. 
Objectives and Endpoints .............................................................................................................. 15 
5.1. Objectives ............................................................................................................................................ 15 
5.1.1. 
Study Objective ........................................................................................................................... 15 
5.1.2. 
Primary Objective ....................................................................................................................... 15 
5.1.3. 
Secondary Objective ................................................................................................................... 15 
5.1.4. 
Exploratory Objective ................................................................................................................. 15 
5.2. Endpoints ............................................................................................................................................. 15 
5.2.1. 
Primary Endpoint ........................................................................................................................ 15 
5.2.2. 
Secondary Endpoints .................................................................................................................. 15 
5.2.3. 
Additional Exploratory Endpoints ............................................................................................... 16 
5.2.4. 
Rationale ..................................................................................................................................... 16 
6. 
Study Design ................................................................................................................................. 16 
6.1. Duration ............................................................................................................................................... 16 
6.2. Study Oversight ................................................................................................................................... 16 
6.3. Trial Organization ................................................................................................................................ 17 
6.3.1 Participating Sites ............................................................................................................................ 17 
6.3.2 Site Principal Investigator ................................................................................................................ 17 
6.3.3 Heart Team ...................................................................................................................................... 17 
6.3.4 Publication Committee .................................................................................................................... 18 
6.3.5 Trial Training .................................................................................................................................... 18 
7 
Product Description ...................................................................................................................... 18 

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7.1 Description of Devices ......................................................................................................................... 18 
7.1.1 Medtronic Evolut PRO and Evolut™ PRO+ Systems ........................................................................ 18 
7.2 Manufacturer ......................................................................................................................................... 25 
7.3 Intended Population .............................................................................................................................. 25 
7.4 Product Training Requirements ............................................................................................................. 25 
7.5 Product Labeling, Tracking, and Accountability .................................................................................... 25 
7.6 Product Storage ..................................................................................................................................... 26 
8 Study Site Requirements .................................................................................................................... 26 
8.1 Study Site Activation ............................................................................................................................ 26 
9 Selection of Subjects .......................................................................................................................... 26 
9.1 Study Population ................................................................................................................................. 26 
9.2 Subject Enrollment ................................................................................................................................ 27 
9.2.1 Roll-In Subjects ................................................................................................................................... 27 
9.3 Inclusion Criteria .................................................................................................................................... 27 
9.4 Exclusion Criteria ................................................................................................................................... 27 
10 Study Procedures ............................................................................................................................. 29 
10.1 Schedule of Events ............................................................................................................................... 29 
10.1.1 
Screening Procedures .............................................................................................................. 29 
10.1.2 
Enrollment ............................................................................................................................... 29 
10.1.3 
Implant Procedure (TAVR) ...................................................................................................... 30 
10.1.3.1 
Procedural Angiograms ........................................................................................................... 31 
10.1.4 
Prior to Discharge .................................................................................................................... 31 
10.1.5 
Follow-Up Evaluations ............................................................................................................. 32 
10.1.6 
Additional Evaluations for Pacemaker Implants ..................................................................... 33 
10.1.7 
Missed Follow-Up Visits .......................................................................................................... 34 
10.1.8 
Core Labs ................................................................................................................................. 34 
10.1.9 
Subject Consent....................................................................................................................... 34 
10.2 Revisions in Patient Information and Informed Consent Form ........................................................... 35 
10.3 Assessment of Efficacy ........................................................................................................................ 35 

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10.4 Assessment of Safety ........................................................................................................................... 35 
10.4.1 
Adverse Events and Device Deficiencies ................................................................................. 35 
10.5 Device Malfunction or Explant ............................................................................................................ 36 
10.6 Data Collection .................................................................................................................................... 36 
10.6.1 
Source Documents .................................................................................................................. 37 
10.7 Deviation Handling .............................................................................................................................. 38 
10.8 Subject Exit, Withdrawal or Discontinuation....................................................................................... 38 
11 Risks and Benefits ............................................................................................................................ 39 
11.1 Potential Risks...................................................................................................................................... 39 
11.2 Potential Benefits ................................................................................................................................ 39 
11.3 Risk-Benefit Rationale ......................................................................................................................... 39 
11.3.1 
Risk Minimization .................................................................................................................... 39 
11.3.2 
Alternative Therapies .............................................................................................................. 39 
11.3.3 
Results from the Risk Analysis and Justification for the Study ............................................... 40 
12 Adverse Events and Device Deficiencies ........................................................................................... 40 
12.1 Definitions/Classifications ................................................................................................................... 40 
12.1.1 
Evaluation and Documentation of Adverse Events ................................................................. 42 
12.1.2 
Evaluation and Documentation of Device Deficiencies .......................................................... 43 
12.2 Reporting of Adverse Events ............................................................................................................... 44 
12.3 Emergency Contact Details for Reporting AEs and Device Deficiencies.............................................. 44 
12.4 Product Complaint Reporting .............................................................................................................. 44 
13 Statistical Design and Methods ........................................................................................................ 45 
13.1 General Aspects of Analysis ................................................................................................................. 45 
13.1.1 
Enrolled Population ................................................................................................................. 45 
13.2 Description of Baseline Variables ........................................................................................................ 46 
13.3 Primary Analysis .................................................................................................................................. 46 
13.3.1 
Primary Endpoint .................................................................................................................... 46 
13.4 Sample Size .......................................................................................................................................... 46 
13.5 Secondary Endpoints ........................................................................................................................... 47 

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13.6 Additional Exploratory Endpoints ........................................................................................................ 47 
13.7 Missing Data ........................................................................................................................................ 47 
14 Ethics .............................................................................................................................................. 47 
14.1 Statement of Compliance .................................................................................................................... 47 
15 Study Administration ....................................................................................................................... 48 
15.1. 
Monitoring ..................................................................................................................................... 48 
15.2. 
Data Management ......................................................................................................................... 49 
15.3. 
Direct Access to Source Data/Documents ..................................................................................... 49 
15.4. 
Confidentiality ............................................................................................................................... 49 
15.5. 
Liability .......................................................................................................................................... 49 
15.6. 
CIP Amendments ........................................................................................................................... 50 
15.7. 
Record Retention ........................................................................................................................... 50 
15.8. 
Publication and Use of Information .............................................................................................. 50 
15.9. 
Suspension or Early Termination ................................................................................................... 51 
15.9.1 
Suspension or Early Termination of the Trial .......................................................................... 51 
15.9.2 
Suspension or Early Termination of a Trial Site ...................................................................... 51 
16 Other Institutions and Professional Services ..................................................................................... 51 
17 References ...................................................................................................................................... 51 
18 Appendices ...................................................................................................................................... 54 
18.1 Conduction Disturbance Management ............................................................................................... 54 
18.2 Quality of Life Questionnaires ............................................................................................................. 58 
18.3 Echocardiography Procedure .............................................................................................................. 58 
18.3.1 
Required Exams ....................................................................................................................... 58 
18.3.2 
General Imaging and Recording Procedures ........................................................................... 59 
18.3.3 
List of Recommended Images ................................................................................................. 59 
18.3.4 
Data Requirements ................................................................................................................. 61 
18.3.5 
Acquisition of Key Variables .................................................................................................... 62 
18.3.6 
Core Lab Analysis ..................................................................................................................... 71 
18.4 Recommended MSCT Procedures ....................................................................................................... 73 

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18.4.1 
General requirements ............................................................................................................. 74 
18.4.2 
ECG-gated contrast enhanced scan of aortic root .................................................................. 74 
18.4.3 
Anatomic suitability and valve size selection .......................................................................... 79 
18.5 Resheath and Recapture Definitions ................................................................................................... 79 
18.6 Endpoint Definitions ............................................................................................................................ 80 
19 Version History ............................................................................................................................. 89 
 
 
 

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Exploratory Objective 
The exploratory objective is to collect longer-term clinical evidence on 
the safety and efficacy of the Evolut™ PRO and Evolut™ PRO+ devices, 
as well as collect evidence on hospital readmissions post-TAVR. 
Primary Endpoint 
Rate of all-cause mortality or all-stroke at 30 days 
Secondary Endpoints 
• Median days from index procedure to discharge 
• Percentage of subjects with ≥ moderate aortic regurgitation (AR) at 
discharge. 
• Rate of pacemaker implant for new onset or worsening conduction 
disturbance at 30 days 
Additional Exploratory 
Endpoints 
• 30-day and 1-year hospital re-admission rates 
• 1-year composite of all-cause mortality or all-stroke 
Study Design 
Post-market, multi-center, prospective, non-randomized 
Sample Size 
• Up to 46 sites in the United States and Canada with approximately 
400 attempted implant subjects and 138 roll-in subjects 
• Up to 15 sites in Europe, Middle East, and Africa (EMEA) with at least 
200 subjects and approximately 45 roll-in subjects 
• Up to 7 sites in Australia and New Zealand (ANZ) with approximately 
50 subjects and 21 roll-in subjects 
Patient Population 
Subjects with severe, symptomatic aortic stenosis (AS) necessitating 
valve replacement 
Duration 
Total study duration is estimated to be 4 years (time from first subject 
implanted to one-year follow-up on last subject implanted) 
Key Inclusion Criteria 
• Acceptable candidate for treatment with the Evolut™ PRO or Evolut™ 
PRO+ system in accordance with the commercial Instructions for Use 
and local regulations; 
• Subject is symptomatic from his/her aortic valve stenosis, as 
demonstrated by New York Heart Association (NYHA) Functional 
Class II or greater; 
• Subject and the treating physician agree that the subject will return 
for all required post procedure follow-up visits; 
• Anatomically suitable for transfemoral TAVR with the Medtronic 
TAVR system; 
• Subject meets the legal minimum age to provide Informed Consent 
based on local regulatory requirements; 
Key Exclusion Criteria 
• 
Contraindicated for treatment with the Evolut™ PRO or Evolut™ 
PRO+ system in accordance with the Instructions for Use  

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• 
Anatomically not suitable for the Evolut™ PRO or Evolut™ PRO+ 
system; 
• 
Previous aortic valve replacement; 
• 
Reduced ventricular function with left ventricular ejection fraction 
(LVEF) < 35% as measured by resting echocardiogram; 
• 
Frailty assessments identify: 
o Subject is <80 years of age and three or more of the 
following apply; OR subject is > 80 years of age and two 
or more of the following apply  
 
Wheelchair bound 
 
Resides in an institutional care facility (eg. 
nursing home, skilled care center) 
 
Body Mass Index <20kg/m2 
 
Grip strength <16kg 
 
Katz Index score ≤4 
 
Albumin <3.5 g/dL 
• 
Bicuspid valve verified; 
• 
Aortic root angulation (angle between plane of aortic valve annulus 
and horizontal plane/vertebrae) > 70°.   
• 
Implanted with pacemaker or ICD; 
• 
Prohibitive left ventricular outflow tract calcification; 
• 
Estimated life expectancy of less than 12 months due to associated 
non-cardiac co-morbid conditions; 
• 
Other medical, social, or psychological conditions that in the opinion 
of the Investigator precludes the subject from appropriate consent, 
adherence to the protocol required follow-up exams; 
• 
Currently participating in an investigational drug or another device 
trial (excluding registries); 
• 
Need for emergency surgery for any reason; 
• 
Subject is less than legal age of consent, legally incompetent, or 
otherwise vulnerable.  
Study Procedures and 
Assessments 
• Clinical assessment at baseline, discharge, 30 days, and 1 year 
• Transthoracic echo at baseline, discharge, and 1 year 
• Multi-Detector Computed Tomography at baseline 
• Quality of Life pre and post-procedure, 30 days, and 1 year 

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• 12-lead ECG at pre and post-procedure, discharge, 30 days, and 1 
year 
4. Introduction  
4.1. Background and Rationale 
Transcatheter aortic valve replacement (TAVR) has been shown to be a safe and effective treatment for 
patients with severe aortic stenosis who are at extreme, high, or intermediate surgical risk(1-3).  Since 
CoreValve™ became commercially approved in the Europe in 2007, and in United States by the Food and 
Drug Administration (FDA) in 2014, the procedure and valve iterations have become increasingly efficient 
with reducing complications.  The Evolut™ PRO and Evolut™ PRO+ valve’s outer pericardial wrap was 
designed  to enhance annular sealing to promote a decrease in paravalvular leak(4).  There is also a growing 
shift towards optimizing the TAVR care pathway by protocolizing the pre, peri, and post procedure 
assessments.  This optimization can further increase the efficiency of the procedure and subsequently 
decrease the length of hospital stay and reduce health care costs(5,6).     
This procedural efficiency has not translated to a consistent reduction in permanent pacemaker 
implantation (PPI) rates.  Rates have decreased with newer generation TAVR valves, however, variability 
continues(7).  There is a lack of consensus regarding the management of post-TAVR conduction 
abnormalities leading towards heterogenous PPI rates across institutions and potentially unnecessary 
pacemaker implantations for abnormalities that could have resolved intrinsically over time(8,9).  Previous 
studies indicate most of high degree atrioventricular block (HAVB) and left bundle branch block (LBBB) 
occur prior to hospital discharge, and early monitoring is key to identifying and managing persistent TAVR-
induced conduction abnormalities(10,11).   
The objective of this study is to collect outcome data on valve performance while following a pre-specified 
TAVR care pathway.  Additionally, this study will protocolize the management of the post-TAVR conduction 
disturbances and evaluate whether a consistent deployment technique will reduce the variability of new 
onset conduction disturbances.  
This study will collect safety and performance data on guidewires and sheaths that are used during the 
TAVR procedure.  
4.2. Purpose 
The purpose of this study is to collect clinical evidence on valve performance and procedural outcomes 
associated with an “optimized” TAVR care pathway and using the Evolut™ PRO and Evolut™ PRO+ devices. 

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5. Objectives and Endpoints 
5.1. Objectives 
5.1.1. 
Study Objective  
The study objective is to collect post-market clinical evidence on valve performance and procedural 
outcomes associated with an “optimized” TAVR care pathway and post-TAVR conduction disturbance 
pathway while using the Evolut™ PRO and Evolut™ PRO+ devices. 
5.1.2. 
Primary Objective 
The primary objective is to collect short-term clinical evidence on the safety of the Evolut™ PRO and 
Evolut™ PRO+ devices. 
5.1.3. 
Secondary Objective 
The secondary objective is to collect clinical evidence on valve performance and procedural outcomes. 
5.1.4. 
Exploratory Objective  
The exploratory objective is to collect longer-term clinical evidence on the safety of the Evolut™ PRO and 
Evolut™ PRO+ devices, as well as collect evidence on reasons for hospital readmissions post-TAVR. 
 
5.2. Endpoints 
The following endpoints will be used to evaluate the study objective as noted in sections 5.1.1, 5.1.2, 5.1.3, 
and 5.1.4. 
5.2.1. 
Primary Endpoint 
The primary endpoint is the rate of all-cause mortality or all-stroke at 30 days. 
5.2.2. 
Secondary Endpoints 
The following are the secondary endpoints: 
• 
Median days from index procedure to discharge 
• 
Percentage of subjects with ≥ moderate aortic regurgitation (AR) at discharge 
• 
Rate of pacemaker implant for new onset or worsening conduction disturbance at 30 days 

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5.2.3. 
Additional Exploratory Endpoints  
The following are additional exploratory endpoints: 
• 
30-day and 1-year hospital re-admission rates 
• 
1-year composite of all-cause mortality or all-stroke 
5.2.4. 
Rationale 
The basis for the selection of these study endpoints include: 
• 
Clinically relevant outcomes of the Evolut™ PRO and Evolut™ PRO+ devices 
• 
In accordance with objectively measuring the efficacy of an optimized care pathway for TAVR 
subjects 
• Objectively defined and measurable in the majority of subjects 
• Consistent with current recommendations for endpoints in TAVR clinical studies(12)  
6. Study Design  
This is a post market, multi-center, prospective, non-randomized, interventional study.  The study methods 
include the following measures to minimize potential sources of bias: 
• 
An external, 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. 
• 
All sites will follow a standardized protocol for acquisition of echocardiographic endpoint data. 
• 
Core labs will evaluate all echocardiograms and ECGs.  Echocardiographic trial endpoint results 
will be based on Core Lab assessments. 
• 
Subjects will be screened to confirm eligibility for enrollment with pre-defined inclusion and 
exclusion criteria. 
6.1. Duration 
The enrollment period is estimated to be approximately 36 months and subjects will be followed for up to 
one year post index procedure; therefore, the estimated total duration of the study (first subject enrolled 
to last subject completing his/her last follow-up exam) is estimated to be approximately 4 years.  
6.2. Study Oversight 
The study will utilize a Steering Committee. The Steering Committee advises on the scientific content of the 
study and provides input for the execution. Members may be study site investigators. The purpose of the 
Steering Committee is to provide unbiased opinions and expertise to the clinical study design and process. 
The Steering Committee will support the execution of the Optimize PRO study and provide guidance, 

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feedback, and direction to the study. The Steering Committee is comprised of the members as indicated in 
the Steering Committee Charter.  
The study will utilize a Screening Committee. The Screening Committee will be utilized when final 
confirmation of approval is required for a subject to be approved into the study. The Screening Committee 
is comprised of the members as indicated in the Screening Committee Charter. 
6.3. Trial Organization 
6.3.1 Participating Sites 
This trial may be conducted at up to 46 sites in the United States and Canada, up to 15 sites in EMEA, and 
up to 7 sites in ANZ.  Investigative sites will meet the following criteria: 
• 
The site will have extensive facility experience with TAVR.  Operator 1 and Operator 2 must 
individually meet the minimum of  ≥ 20 TAVR procedures in the prior year, or ≥ 40 TAVR procedures 
in the prior two years.  
• 
The site will have the presence or capacity of establishing an investigative team consisting of the 
following: 
o Minimum of 2 TAVR implanters with expertise in transcatheter aortic valve replacement as 
noted above 
o Electrophysiologist  
o Echocardiographer 
o Trial coordinator 
6.3.2 Site Principal Investigator 
Each site will have a Principal Investigator (PI) who is a TAVR implanter among the Heart Team.  The PI will 
have overall responsibility for the conduct of the study at the site, including protecting the rights, safety, 
and welfare of the study subjects at their site, the integrity of the trial data generated by their site, and for 
ensuring the trial is conducted in compliance with the Clinical Investigation Plan and IRB/REB/EC 
requirements. 
6.3.3 Heart Team 
Each site will utilize a local Heart Team to assess eligibility of the prospective subject for the trial according 
to the site’s standard process and payer requirements. 
At a minimum, the local Heart Team should include the TAVR implanter.  The site PI may also serve as a 
member of the Heart Team. 

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6.3.4 Publication Committee 
A Publication Committee will provide direction and support in the development of clinical publications.  The 
Publication Committee will consist of steering committee members.  The Publication Committee will be 
responsible to: 
• 
Define the publication plan 
• 
Review, approve, and prioritize publication proposals 
• 
Provide input on the scientific merit and clinical relevance of ancillary publications 
• 
Identify the manuscript/abstract first author(s)/writer(s)/presenter(s) 
• 
Review publications prior to submission 
 
The Committee will be in charge of publication efforts until the completion of the primary endpoint.  All 
publication activities post the primary endpoint will be facilitated by the Medtronic TAVR Global Evidence 
Committee.   
6.3.5 Trial Training 
Prior to participating, center activation, or subsequent involvement in study activities, Medtronic will 
provide training to the investigative team on the trial methods, procedures, and requirements.  Training 
may be conducted via site initiation visits, investigator meetings, and/or other media sessions.  Medtronic 
and the site will maintain documentation of these training sessions.  Additionally, Medtronic 
representative(s) may be present at each site’s implant procedures as part of the ongoing procedure 
support process. 
7 Product Description 
7.1 Description of Devices  
All products used in this study will be market released in the geographies they are used. 
7.1.1 Medtronic Evolut PRO and Evolut™ PRO+ Systems 
The Medtronic Evolut PRO System is a TAVR implantation system comprised of the following 3 components 
(Table 1): 
• 
Medtronic Evolut PRO TAV 
• 
Medtronic EnVeo PRO DCS with EnVeo InLine Sheath  
• 
Medtronic EnVeo PRO LS  
 

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Figure 2. (A) Evolut PRO+ TAV; (B) Evolut PRO+ 23-29mm DCS; (C) Evolut PRO+ 34mm DCS (D) Evolut PRO+ 23-29mm 
LS (E) Evolut PRO+ 34mm LS 
7.1.2.1 Medtronic Evolut PRO Transcatheter Aortic Valve 
The Evolut PRO TAV is available in 3 sizes (23, 26, 29 mm), covering an aortic annulus diameter of 18 to 26 
mm. For the 26mm and 29mm bioprostheses: If the patient’s annulus diameter is within 0.5 mm of the 
upper or lower bound of the range, use of the larger valve size can be considered, provided additional 
dimensional criteria as outlined in the CIP are met. The TAV is comprised of 3 leaflets, a sealing skirt, and 
outer tissue wrap constructed from glutaraldehyde-fixated porcine pericardium, sewn to a compressible 
and self-expandable Nitinol support frame. The TAV is processed with an anti-mineralization treatment of 
AOATM, a compound derived from oleic acid, a naturally occurring long-chain fatty acid. 

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7.1.2.2 Medtronic Evolut PRO+ Transcatheter Aortic Valve 
The Medtronic Evolut PRO+ TAV is available in certain geographies in 4 sizes (23, 26, 29, 34mm), covering 
an aortic annulus diameter of 18 to 30 mm. For the 26mm and 29mm bioprostheses: If the patient’s 
annulus diameter is within 0.5 mm of the upper or lower bound of the range, use of the larger valve size 
can be considered, provided additional dimensional criteria as outlined in the CIP are met. The TAV is 
comprised of 3 leaflets, a sealing skirt, and outer tissue wrap constructed from glutaraldehyde-fixated 
porcine pericardium, sewn to a compressible and self-expandable Nitinol support frame. The TAV is 
processed with an anti-mineralization treatment of AOA, a compound derived from oleic acid, a naturally 
occurring long-chain fatty acid. 
7.1.2.3 Medtronic EnVeo PRO Delivery Catheter System with EnVeo InLine 
Sheath 
The EnVeo PRO DCS facilitates the placement of the TAV within the annulus of the aortic valve. 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.  Updates to the system include redesign of the 
distal tip of the DCS. 
The EnVeo InLine Sheath 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 for the 23 mm, 26 
mm, and 29 mm Evolut PRO system is compatible with a 20 Fr introducer.  
The DCS 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 accurate 

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placement of the bioprosthesis frame paddles during loading. In addition, the device packaging is swiveled 
and secured to facilitate the bioprosthesis loading procedure. 
7.1.2.4 Medtronic Evolut PRO+ Delivery System 
The Evolut PRO+ catheter facilitates the placement of the bioprosthesis within the annulus of the aortic 
valve. 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 the 
bioprosthesis to be partially or fully recaptured 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. A PRO+ 
InLine sheath is assembled over the stability layer, which functions as a hemostatic introducer sheath and 
minimizes the access site size to the capsule diameter. The catheter is compatible with an 18 Fr (6.0 mm) 
introducer sheath for the 23, 26, and 29 mm TAVs and a 22 Fr (7.3 mm) introducer sheath for the 34 mm 
TAV. 
The DCS consists of a catheter with an integrated handle to assist 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 
deployment knob turns to deploy the bioprosthesis. Arrows on the deployment knob indicate the direction 
of rotation required to deploy the bioprosthesis. If desired, the deployment knob can be turned in the 
opposite direction to partially or fully recapture the bioprosthesis if the radiopaque capsule marker band 
has not yet reached the distal end of the radiopaque paddle attachment. Once the radiopaque capsule 
marker band reaches the distal end of the radiopaque paddle attachment, it is at the point of no recapture. 
The deployment knob also features a trigger, which can be engaged to make macro adjustments to the 
capsule position. A blue hand rest connects to the deployment knob. 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 accurate 
placement of the bioprosthesis frame paddles during loading. In addition to these features, the device 
packaging is swiveled and secured to facilitate the bioprosthesis loading procedure. 
7.1.2.5 EnVeo PRO Loading System 
The EnVeo PRO LS is a system of reduction cones and tubing designed to gradually reduce the diameter of 
the TAV radially to an optimal diameter to facilitate manual loading of the Evolut PRO TAV into the 
deployment sheath capsule of the EnVeo PRO DCS. The EnVeo PRO loading system incorporates minor 
modifications including a change to the capsule guide tube (CGT) to include a locking collar, which reduces 
the ability of the user to load the TAV with a paddle in the incorrect position by preventing movement of 
the frame paddles once positioned in the spindle pockets. Additionally, manufacturing process changes and 

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a minor design and material change, including the color differentiation between the two loading system 
sizes, was implemented on the catheter tip guide tube (TGT) components. A third modification is to the 
inner diameter of the inflow ring designed to allow multiple TAVs to seat securely into the inflow ring.   
7.1.2.6 Evolut PRO+ Loading System 
The Evolut PRO+ LS compresses the bioprosthesis into the catheter. Note: verify the correct delivery 
system and loading system are used for the Evolut PRO+ 34 mm valve. This loading system is designed for 
compatibility with this specific TAV and delivery system. 
7.2 Manufacturer 
The legal manufacturer and design site of the Evolut PRO and Evolut PRO+ systems is as follows: 
Medtronic CoreValve LLC 
 
  
7.3 Intended Population 
The study population includes patients with symptomatic native aortic valve stenosis necessitating valve 
replacement.  Patients who undergo an emergency procedure should not be included in this study.   
7.4 Product Training Requirements 
The Evolut PRO and Evolut PRO+ devices will be used within the local commercially approved indication in 
the geographies in which each device is approved, with exception to any inclusion and exclusion criteria in 
this protocol and obtained by the study sites according to standard hospital procedures for commercial 
products.  Local existing approved procedures for commercial product regarding training, distribution, 
shipment, storage, and handling will be followed. In the event of a device malfunction or explant, please 
refer to section 10.5.  
7.5 Product Labeling, Tracking, and Accountability  
Subjects enrolled in this study will be treated using commercial product.  Device lot and serial numbers, as 
applicable, will be collected in the Device Identification CRF.  As this is not an investigational trial, Product 
Accountability Logs (PALs) will not be utilized.  Sites will follow their institutional standard practice for 
device ordering and replenishment of commercial product for use in this study.   
   

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7.6 Product Storage 
Sites will follow their institutional standard practice for storing commercial TAVR product. 
 
8 Study Site Requirements 
8.1 Study Site Activation 
During the activation process (prior to subject enrollment), Medtronic will train study site personnel on the 
clinical investigation plan, informed consent, and on data collection and reporting tools. If new members 
join the study site team, they will receive training on the applicable study requirements relevant to their 
role before contributing to the study. 
Prior to performing study related activities, all regulatory requirements shall be fulfilled, including, but not 
limited to the following:  
• 
IRB/REB/EC approval (and voting list, as required by local law) of the current version of the CIP 
and IC.  
• 
Fully executed CTA: Medtronic contracts with participating institutions/investigators through a 
Clinical Trial Agreement that defines the scope and responsibilities and associated 
compensation related to carrying out the obligations under a clinical study sponsored by 
Medtronic. 
• 
CV of investigators and key members of the investigation study site team (as required ). The 
signature on the CV must be dated within 3 years prior to the date of activation of the study 
site.   
• 
Documentation of delegated tasks 
• 
Documentation of study training 
In addition, all participating study site staff must be trained on the current version of the CIP as well as on 
the applicable study requirements depending on their role and must be delegated by the principal 
investigator to perform study related activities.   
Medtronic will provide each study site with documentation of study site/investigator readiness; this letter 
must be received prior to performing study related activities. 
 
9 Selection of Subjects 
9.1 Study Population 
The study population includes patients with symptomatic native aortic valve stenosis that necessitates 
valve replacement who meet the criteria for on-label use of the Evolut PRO and/or Evolut PRO+ system in 
accordance with Instructions for Use and local regulations. 

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9.2 Subject Enrollment 
This study will involve approximately 650 subjects in the US, Canada, EMEA, and ANZ (not including roll-in 
subjects) based on the number of subjects with an attempted TAVR procedure among all active sites.  To 
ensure a widespread distribution of data and to minimize bias in the study results, no site will implant more 
than 50 subjects without prior authorization from Medtronic.  Subjects who exit from the study after 
implantation will not be replaced.   
9.2.1 Roll-In Subjects 
For all participating centers, the first three subjects implanted will be considered “roll-in” subjects and will 
not be included in the 650 ‘attempted implant’ cohort.   The purpose of the roll-in subjects is to provide 
Investigators the time for training and familiarization with the protocolized implant technique.  The Training 
and Education team will review and provide recommendations for transition of sites from roll-in phase to 
attempted implant analysis phase. Medtronic will notify each site with official correspondence on approval 
to move into the as-treated analysis phase.  
Roll-in subjects will complete in-clinical follow-up evaluations as noted in section 10.1.5 Follow-Up 
Evaluations however the results for the roll-in population will be analyzed separately from the primary 
analysis cohorts.  
9.3 Inclusion Criteria 
Prospective subjects must meet all of the following inclusion criteria to be eligible for participation: 
1. Acceptable candidate for treatment with the Evolut PRO or Evolut PRO+ system in accordance with 
the commercial Instructions for Use and local regulations; 
2. Subject is symptomatic from his/her aortic valve stenosis, as demonstrated by New York Heart 
Association (NYHA) Functional Class II or greater; 
3. Subject and the treating physician agree that the subject will return for all required post procedure 
follow-up visits; 
4. Anatomically suitable for transfemoral TAVR with the Medtronic TAVR system; 
5. Subject meets the legal minimum age to provide Informed Consent based on local regulatory 
requirements. 
9.4 Exclusion Criteria 
Subjects are not eligible for study participation if they meet ANY of the following exclusion criteria: 
1. Contraindicated for treatment with the Evolut PRO or Evolut PRO+ system in accordance with the 
Instructions for Use  

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2. Anatomically not suitable for the Evolut PRO or Evolut PRO+ system; 
3. Reduced ventricular function with left ventricular ejection fraction (LVEF) < 35% as measured by 
resting echocardiogram; 
4. Previous aortic valve replacement; 
5. Frailty assessments identify: 
o Subject is <80 years of age and three or more of the following apply; OR subject is > 80 
years of age and two or more of the following apply  
 
Wheelchair bound 
 
Resides in an institutional care facility (e.g. nursing home, skilled care center) 
 
Body Mass Index <20kg/m2 
 
Grip strength <16kg 
 
Katz Index score ≤4 
 
Albumin <3.5 g/dL 
6. Bicuspid valve verified; 
7. Aortic root angulation (angle between plane of aortic valve annulus and horizontal 
plane/vertebrae) > 70°.   
8. Implanted with pacemaker or ICD; 
9. Prohibitive left ventricular outflow tract calcification; 
10. Estimated life expectancy of less than 12 months due to associated non-cardiac co-morbid 
conditions; 
11. 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; 
12. Currently participating in an investigational drug or another device trial (excluding registries); 
13. Need for emergency surgery for any reason. 
14. Subject is less than legal age of consent, legally incompetent, or otherwise vulnerable*. 
 
* Notes: Vulnerable subjects include individuals whose willingness to volunteer in a clinical investigation 
could be unduly influenced by the expectation, whether justified or not, of benefits associated with 
participation or of retaliatory response from senior members of a hierarchy in case of refusal to participate.  
EXAMPLE Individuals with lack of or loss of autonomy due to immaturity or through mental disability, 
persons in nursing homes, children, impoverished persons, subjects in emergency situations, ethnic minority 
groups, homeless persons, nomads, refugees, and those incapable of giving informed consent. Other 
vulnerable subjects include, for example, members of a group with a hierarchical structure such as 
university students, subordinate hospital and laboratory personnel, employees of the sponsor, members of 
the armed forces, and persons kept in detention. (13) 

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10 Study Procedures 
10.1 Schedule of Events 
Follow-up protocol required evaluations should be performed at the trial site, however remote visits via 
phone contact are permitted, if necessary.  The protocol required evaluations for each trial interval are 
listed as follows and summarized in Table 3. 
10.1.1 
Screening Procedures  
The following assessments must be completed within 12 weeks prior to TAVR index procedure unless 
otherwise indicated: 
• 
Clinical assessment, history, and concomitant medications  
o Physical examination including height, weight, systolic and diastolic blood pressure, and body 
surface area. 
o 5-Meter Gait Speed 
o Grip Strength 
• 
NYHA classification 
• 
MSCT angiogram – within 1 year prior to procedure 
• 
TTE – within 10 weeks prior to procedure 
• 
Heart Team eligibility assessment 
• 
Laboratory tests – glomerular filtration rate (GFR), hemoglobin, international normalized ratio (INR) for 
subjects on warfarin, and serum creatinine  
• 
Modified Rankin Score – conducted by certified site personnel 
• 
Quality of Life Questionnaires 
o EQ-5D 
o KCCQ 
• 
STS Risk Score 
• 
Katz Index of Independence in Activities of Daily Living 
 
The Optimize PRO study will include a Confirmation of Qualification process conducted by Medtronic 
Clinical Analysts and an independent Screening Committee to review the anatomical characteristics of 
potential subjects identified by the sites for enrollment.  Depending on whether a subject’s anatomical 
characteristics meet entry criteria for the study, a recommendation to proceed with treatment or to re-
evaluate / exit the subject will be provided to the site.   
10.1.2 
Enrollment 
Subjects will be considered enrolled into the study at the time of Informed Consent.  Due to the 
inclusion/exclusion criteria, not all patients enrolled in the study will be treated. All sites will be required 

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to maintain a record of patients screened for the trial meeting general inclusion criteria who have signed 
the approved Informed Consent document.  For subjects that do not meet study criteria, the reason for 
not continuing in the trial must be documented and recorded in the EDC system.  
Pediatric, legally incompetent, or otherwise vulnerable patients are not eligible for the trial.  Further, the 
Medtronic TAVR system will not be used as an emergency treatment. 
Subjects must have their TAVR procedure as soon as possible and no later than 90 days post-enrollment. 
10.1.3 
Implant Procedure (TAVR) 
Procedural aspects specific to the Medtronic TAVR system should be performed according to the 
Instructions for Use.  Concomitant procedures including percutaneous coronary intervention (PCI) are not 
permitted to be completed during the index procedure.   
The valve deployment will be completed in accordance to the cusp overlap technique via procedural  
angiogram, and the standard procedures of the implanting physicians and the TAVR clinical pathway 
protocol requirements noted below. This described TAVR clinical pathway should serve as a guide for 
accelerated discharge.  Institutional clinical TAVR pathways can be followed as long as the modifications are 
consistent with an accelerated discharge. 
Pre-procedure: 
• 
12-lead ECG – within 48 hours prior to procedure  
• 
Develop “early discharge plan” (including frailty, mental assessment, and home health if required) with 
multi-disciplinary team along with optimized screening checklist for first and / or second visit leading 
up to TAVR procedure.    
• 
Standardize room layout – team composition in procedure room (planning with multi-disciplinary 
team).    
 
Peri-Procedure: 
• 
No pre-deployment balloon aortic valvuloplasty TAVR procedure unless medically necessary  
• 
General anesthesia should be avoided unless deemed necessary (e.g. for placement of a 
transesophageal echo), and it is believed that its use will not impede an early discharge 
• 
Percutaneous and transfemoral access only 
• 
No urinary catheter 
• 
Minimize central lines: no Swan-Ganz catheterization or internal jugular vein unless for temporary 
transvenous pacing 
 
Post Procedure Recovery: 
• 
Complete 12-lead ECG within 2 hours after the TAVR procedure 

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o If no ECG changes compared to pre-procedure ECG and subject did not have pre-existing RBBB: 
 
Remove all remaining lines within 2 hours of TAVR procedure 
 
Repeat 12-lead ECG prior to discharge to confirm no new ECG changes 
o Refer to Appendix 18.1 Conduction Disturbance Management if new ECG changes or subject 
had pre-existing RBBB 
• 
Mobilize within 4 - 6 hours of TAVR procedure 
• 
Minimal intensive care unit (ICU) utilization: consider post-anesthesia care unit (PACU) in place of ICU 
or transfer straight to stepdown floor or telemetry unit 
10.1.3.1 
Cusp Overlap Procedural Steps  
Ensure the following procedural steps are captured in the recorded fluoroscopy and submitted to 
Medtronic in DICOM format. 
 
1. Conduct initial deployment in the cusp overlap projection and conduct aortogram to obtain the 
estimated implant depth at the NCC.  
2. Use of Double Curved Lunderquist guidewire is highly recommended unless clinically 
contraindicated. 
3. Ensure guidewire is properly positioned within the left ventricle. 
4. Begin deployment with the marker band positioned at mid-pigtail or higher. 
5. Do not exceed 3mm depth at the NCC prior to full annular contact. 
6. Initiate pacing at the third node and rapidly deploy to point of no recapture (80% deployment). 
7. Discontinue pacing at point of no recapture. 
8. Assess depth in cusp overlap view at 80% deployment. 
9. At the point of no recapture, roll LAO (at least 25˚) and remove any remaining parallax at the inflow 
of the TAV. Conduct pre-release aortogram to obtain the estimated depth of implant from this view 
at the LCC (80% deployment). 
10. Determine if appropriate to deploy or recapture (recapture or resheath if depth at NCC is <1mm or 
>5mm). 
11. Redeployment in cusp overlap view, if applicable. 
12. Retract the wire prior to release. 
13. Demonstrate very slow release of the TAV. 
14. Centralize the nosecone prior to withdrawal of the delivery catheter system. 
15. Assess final implant depth on the NCC by aortography in the original cusp overlap projection.  
10.1.4 
Prior to Discharge  
• 
Physical examination including weight, systolic and diastolic blood pressure, and concomitant 
medications. 
• 
NYHA classification 
• 
12-lead ECG (refer to Appendix 18.1 Conduction Disturbance Management for discharge 12-lead 
ECG requirements for subjects with conduction abnormalities) 

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• 
Laboratory tests - glomerular filtration rate (GFR), hemoglobin, international normalized ratio (INR) 
for subjects on warfarin, and serum creatinine  
• 
TTE – should be done between 12 hours and 7 days post TAVR  
• 
Adverse event review 
10.1.5 
Follow-Up Evaluations 
All treated subjects will undergo follow-up evaluations at the following time points post procedure. All 
follow-up periods are defined as the number of days after the date of the index procedure. 
 
Day 0 = day of index procedure 
• 
30 days (30 + 14 days) 
• 
12 months (365 ± 30 days) 
 
30 Days  
• 
Physical examination including weight, systolic and diastolic blood pressure, and concomitant 
medications. 
• 
NYHA classification 
• 
12-lead ECG 
• 
Quality of Life Questionnaires – KCCQ and EQ-5D 
• 
In-office pacemaker interrogation for subjects implanted with pacemakers post index TAVR procedure 
• 
Adverse event review 
 
12 Months 
• 
Physical examination including weight, systolic and diastolic blood pressure, and concomitant 
medications. 
• 
NYHA classification 
• 
12-lead ECG 
• 
Quality of Life Questionnaires – KCCQ and EQ-5D 
• 
TTE 
• 
In-office pacemaker interrogation for subjects implanted with a pacemaker post index TAVR procedure 
• 
Adverse event review 
 
Other Evaluations 
• 
Creatinine clearance from screening and discharge laboratory tests will be derived by the trial database 
system using the Cockcroft-Gault equation. 
• 
A Modified Rankin Score assessment should be conducted at 1 and 3 months following any stroke 
event. 

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follow-up visit. One copy will be stored at the site and another copy will be sent to Medtronic (device data 
must not be cleared).  A device interrogation (final ‘Interrogate All’)/Save-to-Media (or CareLink™ 
transmission) should also be completed at the time of study exit (prior to 12 months visit) and in the case of 
a death (where possible).  
10.1.7 
Missed Follow-Up Visits 
Every effort should be made to ensure subjects return to the clinic for all protocol required follow-ups.  If 
the subject is unable to return for an in-person clinic visit, the Investigator, or designee, should document in 
the subject record the reason the subject was unable to complete the visit and, if applicable, follow the 
requirements for deviation reporting as outlined in Deviation Handling section.  
The investigator should also make every effort to contact the subject within the visit window to collect the 
subject’s vital status as well as information related to potential adverse events, safety data, and 
hospitalizations. 
10.1.8 
Core Labs  
Transthoracic echocardiography (TTE), ECGs, explants, and angiogram imaging will be sent to core labs for 
central assessment.  Further details of the echocardiography methods are provided in Appendix 18.3. 
10.1.9 
Subject Consent 
Prior to enrolling in the trial, patients should be fully informed of the details of trial participation as 
required by applicable regulations, the site’s IRB/REB/EC and the Declaration of Helsinki.  Informed Consent 
must be obtained from each patient prior to conducting any protocol-induced activities beyond standard of 
care, by using the Informed Consent Form (ICF) approved by that site’s IRB/REB/EC and by Medtronic, Inc.  
All Informed Consent Forms, including Authorization/Data Protection or other consenting forms required 
per local requirements and/or short form consents, must be approved by Medtronic, Inc. prior to use.  The 
ICF must be signed and dated by the patient and by the person obtaining the consent.  Any additional 
persons required by the site’s IRB/REB/EC to sign the Informed Consent Forms must also comply.  
Prior to the patient signing the ICF, the investigator or authorized designee will fully explain to the patient 
the nature of the research, trial procedures, anticipated benefits, and potential risks of participation in the 
trial.  The investigator or delegate will allow adequate time for the patient to read and review the consent 
form and to ask questions.  Signing the ICF serves to document the written and verbal information that the 
investigator or authorized delegate provides to the patient, the patient’s understanding of the information, 
and his/her agreement to participate.  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. 

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The original signed consent form will be retained in the patient’s trial records and a copy of the Informed 
Consent Form will be provided to the patient.  
Patients should give written consent before undergoing any protocol-required testing. However, if any of 
protocol-required baseline/screening evaluations (e.g. echocardiography, MSCT, coronary arteriography, 
lab work) have been performed for clinical diagnostic purposes prior to consenting, they can be used as the 
protocol-required exams, provided they were obtained within the protocol-required time windows and 
contain the necessary information. 
Medtronic will provide each site with the study specific informed consent separately from this CIP. 
10.2 Revisions in Patient Information and Informed Consent Form 
Medtronic will inform the investigators whenever information becomes available that may be relevant to 
the subject’s continued participation in the trial.  The revised information will be sent to the investigator for 
approval and presented to subjects in an updated informed consent (if required by IRB/REB/EC).   
10.3 Assessment of Efficacy 
The following methods will be used for assessing, recording, and analyzing efficacy.  Refer to section 10.1 
Schedule of Events for timing of these assessments. 
• 
STS risk score 
• 
Heart team assessment 
• 
MSCT 
• 
TTE 
• 
12-lead ECG 
• 
NYHA functional classification 
• 
EQ-5D and KCCQ quality of life questionnaires 
10.4 Assessment of Safety 
10.4.1 
Adverse Events and Device Deficiencies  
Serious adverse events (SAE), device deficiencies (DD), and non-serious VARC-2 adverse events (that are 
outlined in Appendix 18.6) will be collected from the time of enrollment until the end of the study or until 
study exit, whichever comes first.  
The safety assessment performed during this study will be based on the relatedness to the TAVR implant 
procedure and the following devices: 
• 
Commercial Study Devices: 

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o Medtronic Evolut™ PRO Transcatheter Aortic Valve (TAV) 
o Medtronic EnVeo™ PRO Delivery Catheter System (DCS) with EnVeo™ InLine Sheath  
o Medtronic EnVeo™ PRO Loading System (LS)  
o Medtronic Evolut™ PRO+ Transcatheter Aortic Valve (TAV) 
o Medtronic Evolut™ PRO+ Delivery Catheter System (DCS)  
o Medtronic Evolut™ PRO+ Loading System (LS) 
• 
Commercial Accessory Devices: 
o Sheath  
o Guidewire 
10.5  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 
that a TAV is explanted after implant (due to reintervention or autopsy), the TAV and/or affected 
components should be returned to Medtronic to the following: 
Medtronic, Inc. 
Attn: Explant Lab [PE#] 1851 E. Deere Avenue 
Santa Ana, CA 92705-5720 
 
Additional details surrounding the device return process are contained within the Medtronic explant kit that 
will be provided upon notification of a device malfunction or explant. 
10.6 Data Collection 
Trial sites will assign a unique ID number to each subject.  Records of the subject/subject ID relationship will 
be maintained by the trial site.  Individual subject medical information obtained as a result of this trial will 
be considered confidential. 
This trial will utilize an Oracle Clinical Remote Data Capture (RDC) system that is the property of Medtronic.  
Required data will be recorded on electronic case report forms (eCRFs) by authorized site personnel as 
indicated on the Delegation Task List (DTL).  Trial personnel delegated for eCRF completion and/or approval 
per the DTL will be trained on the use of the RDC system and thereafter provided with a username and 
password to access the system.  The eCRFs must be completed and/or updated to reflect the latest 
observations on the subjects participating in the trial.  The investigator (or approved sub-investigator) will 
electronically sign the appropriate pages of each eCRF. 
Data from the core lab will be entered into the Oracle Clinical RDC system by core lab personnel per their 
procedures established for the trial.  The core lab physician will approve core lab eCRFs. 

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The Oracle Clinical RDC system maintains an audit trail of entries, changes, and corrections in eCRFs.  If a 
person only authorized to complete eCRFs makes changes to an already signed eCRF, the investigator shall 
re-approve this eCRF. 
All trial-related documents must be retained until notified by Medtronic that retention is no longer 
required.  Medtronic will inform the investigator/institution when these documents are no longer required 
to be retained. 
No trial document or image should be destroyed without prior written agreement between Medtronic and 
the investigator.  Should the investigator wish to assign the trial records to another party or move them to 
another location, advance written notice must be given to Medtronic. 
10.6.1 Source Documents 
Entered data must be traceable to source documents. Source data is all information in original records and 
certified copies of original records of clinical findings, observations, or other activities in a clinical trial 
necessary for the reconstruction and evaluation of the trial. Source data are contained in source 
documents. Source documentation is defined as the first time the data appear and may include all clinical 
records, hospital records, procedural reports, autopsy reports, and any other material that contains original 
information used for trial data collection or adverse event reporting.  Identified discrepancies between 
source documents and the eCRFs will be resolved through the on-line query resolution process per the Data 
Management plan. 
The eCRFs may not serve as source documents.  Source documentation for data elements not routinely 
captured in medical records (e.g. echocardiography variables, MSCT variables, catheter and procedural data 
variables, Heart Team assessment, Modified Rankin Score) may vary from center to center.  The site may 
use technical worksheets if identified as source documents. 
Source documents must be retained by the participating site for a period of two years after trial conclusion 
(or longer as required by local law) and made available for monitoring or auditing by the sponsor’s 
representative or representatives of the US FDA and other applicable regulatory agencies or IRB/REB/EC.   
The Investigator must ensure the availability of source documents from which the information on the eCRFs 
was derived.  Where printouts of electronic medical records are provided as original source documents, or 
where copies of source documents are retained as original source documents, they should be signed and 
dated by a member of the investigation site team indicating they are a true reproduction of the original 
source document. 

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10.7 Deviation Handling 
Protocol deviations will be reported regardless of whether medically justifiable, pre-approved by 
Medtronic, or taken to protect the subject in an emergency.   
A protocol deviation is to be completed for each trial protocol deviation, including, 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 IRB/REB/EC approval before the start of the study 
• 
Implanted subject did not meet inclusion/exclusion criteria 
• 
Enrollment of subjects during lapse of IRB/REB/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 well-being 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). 
In addition, Investigators are required to adhere to local IRB/REB/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. 
10.8 Subject Exit, Withdrawal or Discontinuation  
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 trial subjects.  If a subject is discontinued 
from the trial early, the reason for discontinuation should be documented in the subject file and a Study 
Exit eCRF must be completed.  If discontinuation is because of safety concerns or lack of effectiveness, the 
subject shall be asked to be followed for collection of ongoing safety data outside the clinical investigation.   
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 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.  Subjects will then be deemed lost to 
follow up.  All contact efforts to obtain follow-up must be documented in both the subject’s medical 
records and on the trial eCRFs. 

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If a subject discontinues the trial at any time, is withdrawn from the trial 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 aortic valve patients.  If, for any reason, this is not possible for a particular subject, or if 
a subject needs to change their follow-up site at any time point after conclusion of the trial, investigators 
should refer subjects to a local site with appropriate training and experience in managing patients with 
implanted aortic valves.  
11 Risks and Benefits 
11.1 Potential Risks 
There are possible risks and side effects connected to the Evolut PRO or Evolut PRO+ TAV implant, but 
the risks are the same as  those for an implant of the Evolut PRO or Evolut PRO+ TAV without 
participation in this study. Standard risks associated with the Evolut PRO and Evolut PRO+ systems in the 
study are provided in the Instructions for Use. 
Risks and events will be continuously monitored, assessed and documented by the investigator. 
11.2 Potential Benefits 
Participation in this clinical study will not result in any direct benefit to the patient. Trial subjects implanted 
with an Evolut PRO or Evolut PRO+ device receive the same medical treatment as if they were not 
participating in this post-market study. Participation contributes to expansion of the knowledge base with 
respect to the use of the Evolut PRO and Evolut PRO+ systems in a routine hospital setting. 
11.3 Risk-Benefit Rationale 
11.3.1 
Risk Minimization 
The following measures will be implemented to minimize risks to the trial subjects: 
• 
Implanting physicians will have considerable experience with TAVR 
• 
Study sites will have significant experience with TAVR 
• 
Patients will undergo thorough imaging assessment during their pre-implant workup 
• 
Patients will be rigorously followed over the course of the study 
11.3.2 
Alternative Therapies 
Presently, therapeutic alternatives for patients with the clinical indication targeted for the Medtronic TAVR 
System include the following: 

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NOTE 3: For users or other persons, this definition is restricted to events 
related to investigational medical devices. 
Serious Adverse Event 
(SAE)  
 
(ISO14155:2020 3.45) 
 
 
AE that led to any of the following 
a) 
death, 
b) 
serious deterioration in the health of the subject, users, or other 
persons as defined by one or more of the following:  
1) 
a life-threatening illness or injury, or  
2) 
a permanent impairment of a body structure or a body function, 
including chronic disease, or 
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, 
c) 
fetal distress, fetal death or a congenital abnormality or birth defect 
including physical or mental impairment.(13)  
Note 1: Planned hospitalization for a pre-existing condition, or a procedure 
required by the CIP, without serious deterioration in health, is not 
considered an SAE 
Device Deficiency 
(ISO 14155:2020, 3.19) 
Inadequacy of a medical device with respect to its identify, quality, durability, 
reliability, usability, safety or performance. 
 
NOTE 1: DD includes malfunctions, use errors, and inadequacy in the 
information supplied by the manufacturer including labeling.  
Serious Adverse Device 
Effect (SADE)  
(ISO 14155:2020, 3.44) 
Adverse device effect (adverse event related to the use of an investigational 
medical device) that has resulted in any of the consequences characteristic of 
a serious adverse event. 
Unanticipated Serious 
Adverse Device Effect 
(USADE) 
(ISO 14155:2020, 3.51) 
(Serious adverse) device effect which by its nature, incidence, severity or 
outcome has not been identified in the current risk assessment 
 
NOTE 1: ASADE is an effect which by its nature, incidence, severity or outcome 
has been identified in the risk assessment.  
 
Notes: 
• 
The interpretation of Seriousness will exclude certain interventions considered standard of care 
during hospitalization (e.g. IV hydration, certain medications delivered intravenously due to 
available intravenous access or NPO (nothing by mouth) status, and the delivery of electrolytes to 
maintain electrolyte balance or to address mild electrolyte depletion).  Any nonoral medication or 
fluid delivery used to treat an acute physical decompensation/deterioration episode or to 
otherwise resuscitate a subject will be considered serious by definition in that it prevents a 
permanent impairment of a body structure or deterioration of the health of a subject. 
• 
Planned hospitalization for a pre-existing condition, or a procedure required by the CIP, without 
serious deterioration in health, is not considered a serious adverse event.  

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• 
Hospitalization requires admission for at least 24 hours. 
• 
Ballooning as needed during the implant procedure is standard practice and should not be 
considered a reintervention.  
 
The sponsor and the investigators will use the following definitions to assess the relationship of the serious 
adverse event to the investigational medical device or procedures:  
• 
No Relationship: No relationship between the AE and the administration of study treatment and a 
known relationship to other etiologies such as concomitant medications, surgical procedure, or 
subject’s clinical state. 
• 
Possible Relationship: An AE that follows a reasonable temporal sequence from administration of 
the study treatment and follows a known response pattern to the study treatment but could have 
been produced by the participant’s clinical state or by other therapies. 
• 
Probable Relationship: An AE that follows a reasonable temporal sequence from administration of 
the study treatment; follows a known response pattern to the study treatment; and cannot be 
reasonably explained by the known characteristics of the participant’s clinical state or by other 
therapies. 
• 
Causal Relationship: An AE that follows a plausible temporal sequence from administration of the 
study treatment and follows a known response pattern to the study treatment. The reaction cannot 
be reasonably explained by the known characteristics of the subject’s clinical state or other modes of 
therapy administered to the subject.  
• 
Unknown relationship: Given the information available, sequence and timing of events, it is 
unknown or impossible to determine the relationship of the AE with the study treatment. 
 
Particular attention shall be given to the causality evaluation of unanticipated serious adverse (device) 
events. The occurrence of unanticipated events related to the use of the device (USADE) could suggest 
that the clinical investigation places subjects at increased risk of harm than was to be expected. 
 
12.1.1 
Evaluation and Documentation of Adverse Events  
Investigators are required to evaluate and document in the subject’s medical records all serious adverse 
events, non-serious VARC-2 related events outlined in Appendix 18.6, device deficiencies, and device 
deficiencies with SADE potential (per the definitions in Table 5) observed in trial subjects from the time of 
enrollment until they are exited from the trial.  All SAEs should be followed through their resolution. 
Documented pre-existing conditions are not considered to be reportable unless there is a change in the 
nature or severity of the condition and meets definition of a SAE per definition in Table 5 or a non-serious 
VARC-2 AE in Appendix 18.6.  Pre-existing events should be reported as an SAE in the situation where a new 
treatment has to be started or an existing treatment has to be changed to treat the adverse event and the 
event is accompanied with signs and symptoms. 
Unavoidable events are conditions which do not fulfill the definition of an Adverse Event, meaning those 
medical occurrences, clinical signs (including toward abnormal laboratory findings), diseases or injuries that 

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CRF if the deficiency led to an adverse event (any untoward medical occurrence, unintended disease or 
injury, or untoward clinical signs). 
Device Deficiencies that did not lead to an AE but could have led to a SADE (i.e., if suitable action had not 
been taken, if intervention had not been made, or if the circumstances had been less fortunate) require 
immediate reporting.  
12.2 Reporting of Adverse Events 
Investigators are required to report all serious adverse events (SAE) and non-serious VARC-2 adverse events 
outlined in Appendix 18.6 observed in the study subjects from the point of enrollment until completion of 
follow-up.  
The VARC-2 document provides standardization of endpoint definitions for studies evaluating the use of 
TAVI. This study follows VARC-2 to allow for improved comparability and interpretability of study results. In 
addition, Investigators are obligated to report adverse events in accordance with the requirements and 
timeframes per their reviewing IRB/REB/EC and local regulations, if applicable.  
The Sponsor is obligated to report adverse events and device deficiencies that occur during this trial to the 
IRB/REB/EC as per local requirements.    
12.3 Emergency Contact Details for Reporting AEs and Device 
Deficiencies 
Investigators should contact their Medtronic clinical trial monitor or site manager if they have any 
questions regarding reportable AEs.  Medtronic will provide and maintain a listing of current contact details 
for each site. 
12.4 Product Complaint Reporting  
It is the responsibility of the investigator to report all product complaint(s) associated with a medical device 
distributed by Medtronic, regardless whether they are related to intended use, misuse or abuse of the 
product. Reporting must be done immediately and via the regular channels for market-released products. 
The reporting of product complaints by the clinical team must be done according to the local Standard 
Operating Procedures. Medtronic will notify the Regulatory Authorities (e.g. Competent Authority) as 
applicable for the following incidents immediately upon learning of them and is not limited to AEs and DDs 
only: 
• 
Any malfunction or deterioration in the characteristics and/or performance of a device, as 
well as any inadequacy in the labeling or instructions for use which led or might have led to 
the death or serious deterioration in the state of health of a patient, user, or other person. 

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• 
Any technical or medical reason resulting in withdrawal of a device from the market by the 
manufacturer. 
• 
Any serious deterioration in the state of health, including: 
 
Life-threatening illness or injury 
 
Permanent impairment of a body function or permanent damage to a body 
structure 
 
A condition necessitating medical or surgical intervention to prevent permanent 
impairment of a body function or permanent damage to a body structure 
 
13 Statistical Design and Methods 
13.1 
General Aspects of Analysis 
13.1.1 Enrolled Population 
Within the enrolled population the following analysis sets are distinguished: 
• 
The attempted implant set: The attempted implant set consists of all enrolled subjects with an 
attempted TAVR implant procedure, defined as when the subject is brought into the procedure room 
and any of the following have occurred: anesthesia or conscious sedation administered, vascular line 
placed, TEE placed, or any monitoring line placed. Subjects will be analyzed according to their first 
attempted procedure. Enrolled subjects that do not receive an attempted TAVR implant are to be 
exited from the study. 
• 
The implanted set: The implanted set consists of all the attempted implant subjects who are actually 
implanted with the TAV.  Subjects with an attempted implant that do not actually receive a TAV are to 
be exited from the study following discharge from the index hospitalization. 
• 
Per protocol (PP) set 1 for TAVR care pathway: This per protocol set consists of all implanted subjects 
with percutaneous and transfemoral access only and no concomitant procedures including 
percutaneous coronary intervention (PCI). This per protocol set 1 will be used for the secondary 
endpoint median days from index procedure to discharge. Time zero begins on the date of the first 
attempted implant procedure. 
• 
Per protocol (PP) set 2 for conduction disturbance pathway: This per protocol set consists of all 
attempted implant subjects whose peri and post TAVR index procedure follows the conduction 
disturbance pathway management and cusp overlap technique. This per protocol set 2 will be used for 
the secondary endpoint rate of pacemaker implant for new onset or worsening conduction disturbance 
at 30 days. 
• 
Roll-in: Roll-in subjects will not be analyzed with the attempted implant, implanted, or per protocol set 
and will be analyzed separately using descriptive statistics. See section 9.2.1 for definition of roll-in 
subjects.  

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The primary analysis for the primary endpoint and secondary safety and effectiveness endpoints will use 
the attempted implant set.   
13.2 
Description of Baseline Variables 
Baseline demographic and clinical variables will be summarized for the attempted implant, implanted, and 
per protocol sets.  Continuous variables will be summarized as means, medians, standard deviations, 
interquartile ranges, minima and maxima and categorical variables will be summarized as frequencies and 
percentages.   
13.3 
Primary Analysis 
The study objective and endpoints are descriptive, and no statistical hypothesis testing will be performed.  
The first interim analysis will be conducted after 100 subjects are enrolled in the attempted implant set and 
followed through 30 days post procedure.  
Roll-in subjects will not be included in the primary analysis; however, the data will be summarized 
separately with descriptive statistics.   
The rates of permanent pacemaker implantation at 30 days by region (US/CAN, EMEA, and ANZ) will be 
provided and compared. Additional information regarding this analysis can be found in the TAVR Low Risk 
Post Market Clinical Follow-Up Plan.  
13.3.1 Primary Endpoint 
The primary endpoint is the rate of all-cause mortality or all-stroke at 30 days.  A Kaplan-Meier survival 
analysis will be performed with results summarized at 30 days and 12 months. This endpoint is descriptive, 
and no statistical hypothesis test will be performed. 
13.4 
Sample Size 
The sample size for the attempted implant population from each geography is approximately 400 subjects 
at up to 46 sites in the US and Canada, at least 200 subjects at up to 15 sites in EMEA, and approximately 50 
subjects at up to 7 sites in ANZ. The sample size for the roll-in population is approximately 204 subjects. The 
total combined sample size with all analysis populations is approximately 854 subjects.  
This is not a hypothesis-driven study, therefore the attempted implant set sample size of approximately 650 
subjects was not determined by statistical sample size methods. With >25% of TAVR patients experiencing 
new conduction disturbances10, 650 patients will provide a sufficient sample (~160 patients) to evaluate the 
conduction disturbance management pathway.  

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13.5 
Secondary Endpoints 
The following are the secondary endpoints: 
• 
Median days from index procedure to discharge 
• 
Percentage of subjects with ≥ moderate aortic regurgitation (AR) at discharge 
• 
Rate of pacemaker implant for new onset or worsening conduction disturbance at 30 days 
13.6 
Additional Exploratory Endpoints 
The following are additional exploratory endpoints: 
• 
30-day and 1-year hospital re-admission rates 
• 
1-year composite of all-cause mortality or all-stroke 
13.7 
Missing Data 
Every effort will be undertaken to minimize missing data.  However, some missing data is inevitable, and 
the trial is designed with the expectation that there may be up to 6% of primary data missing at 12 months.  
14 Ethics 
14.1 Statement of Compliance 
 
The study will be conducted in accordance with the protocol, ICH E6 R2 GCP, and ethical principles that 
have their origin in the Declaration of Helsinki. Laws and regulations of the countries in which the study is 
conducted, including data protection laws, will be following.  
In addition, in Europe the study will be conducted in compliance with the Medical Device Regulation (EU) 
2017/745 (MDR). Each site must fulfill all local regulatory requirements prior to enrolling subjects and 
throughout the duration of the study, as applicable. 
Participating sites will not be activated nor begin enrolling subjects until the required approval/favorable 
opinion from the local IRB/REB/EC and regulatory agency has been obtained (as appropriate).   
This trial will be publicly registered prior to first enrollment in accordance with the 2007 Food and Drug 
Administration Amendments Act (FDAAA) and on http://clinicaltrials.gov (PL 110-85, Section 810(a)). 
Prior to enrolling subjects, each investigation site’s IRB/REB/EC will be required to approve the current CIP, 
the Informed Consent Form, and any other written information to be provided to the subjects.  Study sites 
must also utilize IRB/REB/EC approved Health Insurance Portability and Accountability Act (HIPAA) 
Authorization, when applicable. 

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IRB/REB/EC approval of the clinical trial must be received in the form of a letter and provided to Medtronic 
before commencement of the trial at an investigation site.  The approval letter must contain enough 
information to identify the version or date of the documents approved.  IRB/REB/EC roster or letter of 
compliance needs to be provided to allow verification that the investigator, other center trial staff, and/or 
Medtronic personnel are not members of the IRB/REB/EC. If they are members of the IRB/REB/EC, written 
documentation is required stating that he/she did not participate in the approval process.  Investigators 
must inform Medtronic of any change in status of IRB/REB/EC approval once the investigation site has 
started enrollment.  If any action is taken by an IRB/REB/EC with respect to the study, that information will 
be forwarded to Medtronic by the respective investigator. 
In addition to the requirements outlined above, any additional requirements imposed by the IRB/REB/EC or 
regulatory authority shall be followed, if appropriate. 
15 Study Administration 
15.1. Monitoring  
Participating sites will be monitored to ensure compliance with the trial protocol, adherence to applicable 
regulations, and accuracy of trial data.  Monitoring visits will be conducted primarily to ensure the safety 
and well-being of the subjects is preserved.  Sites should provide appropriate access to the source data.  
Site personnel will complete eCRFs following each subject visit.  Trial data submitted will be reviewed 
against subject charts and other sources containing original records of subject data.  Source document 
verification will occur via a risk-based approach as outlined in the Monitoring Plan. 
The progress of the trial will be monitored by: 
• 
On-site or remote review, as deemed appropriate by Medtronic 
• 
Telephone communications between the site personnel (e.g., investigator, trial coordinator) and trial 
monitors 
• 
Review of eCRFs and the associated clinical records 
• 
Review of regulatory documents 
 
Upon study completion, Site Closeout Visits will be conducted as outlined in the Monitoring Plan 
Monitoring and monitoring oversight will be provided by Medtronic 
 
.  Representatives of Medtronic (i.e. contractors and designees) may also act as trial monitors. 
Prior to the first site activation a monitoring plan will be established outlining the above activities, as well as 
trial materials to be supplied to sites, the process for corrective and preventive actions and Investigator 
disqualification procedures.  

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15.2. Data Management 
Medtronic will be responsible for the processing and quality control of the data.  Data review, database 
cleaning and issuing and resolving data queries will be done according to Medtronic internal SOPs and the 
Data Management Plan for this trial.  The trial database will be developed and validated per the Data 
Management Plan for this trial and will employ validation programs (e.g. range and logic checks) on entered 
data to identify possible data entry errors and to facilitate data validation.  The trial database will maintain 
an audit trail of all changes made to the eCRFs.   
Refer to Recording Data section for further information regarding data collection and management 
procedures.  
15.3. Direct Access to Source Data/Documents  
Medtronic may conduct audits at participating clinical sites.  The purpose of an audit is to verify the 
performance of the monitoring process and the trial conduct, independent of the personnel directly 
involved in the trial.   
The investigator and/or institution shall permit Medtronic, regulatory bodies, and IRB/REB/EC direct access 
to source data and documents. 
15.4. Confidentiality 
All information and data sent to parties involved in trial conduct concerning subjects or their participation 
in this trial will be considered confidential.  Trial sites will assign a unique subject ID number (SID) to each 
subject.  Records of the subject/SID relationship will be maintained by the trial site.  The SID is to be 
recorded on all trial 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 trial 
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. 
15.5. Liability 
Medtronic, Inc (including all wholly owned subsidiaries) maintains appropriate clinical trial liability 
insurance coverage as required under applicable laws and regulations and will comply with applicable law 
and custom concerning specific insurance coverage.  If required, a Clinical Trial Insurance 
statement/certificate will be provided to the IRB/REB/EC if required. 

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15.6. CIP Amendments 
The investigator may propose any appropriate modification(s) of the CIP.  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 investigators to obtain approval from their IRB/REB/EC.  The investigator will only implement the 
amendment after approval of the IRB/REB/EC, and Medtronic.  Administrative amendments to the CIP will 
be submitted to the IRB/REB/EC for notification.  Furthermore, investigators shall sign any approved 
amendment for agreement. 
Medtronic will maintain a list of internal CIP approvers separate from this document. 
15.7. Record Retention 
At a minimum, the investigator must retain records for at least 2 years (or in accordance with local law) or 
at least two years have elapsed since the formal discontinuation of clinical development of the devices.  
The investigator should take measures to prevent accidental or early destruction of the trial related 
materials. 
15.8. Publication and Use of Information 
Medtronic is committed to the widespread dissemination of all primary and secondary endpoint results.  A 
Publication Plan will be implemented and followed.  At the conclusion of the trial, a multisite abstract 
reporting the primary results will be prepared by the Principal Investigators (in collaboration with others 
including but not limited to the echo core lab physicians, and the CEC).  A multisite publication will similarly 
be prepared for publication in a reputable scientific journal.  The publication of the principal results from 
any single site experience within the trial is not allowed until both the preparation and publication of the 
multisite results, and then only with written permission from Medtronic and the Study Publication 
Committee. 
Following analysis and presentation of the endpoint results, active participation of all participating 
investigators, CEC committee members, and core laboratory personnel will be solicited for data analysis 
and abstract and manuscript preparation.  Submission of all abstracts and publications regarding the 
primary endpoint and secondary endpoints from the trial requires approval by the Principal Investigators 
after review by the Publications Committee. 
A separate Publication Plan will provide detailed information about the publication committee, authorship, 
publication proposals, and requests for data. 

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15.9. Suspension or Early Termination 
15.9.1 
Suspension or Early Termination of the Trial 
If the trial is terminated prematurely or suspended, Medtronic shall promptly inform the clinical 
investigators of the termination or suspension and the reason(s) for this.  The investigator shall then 
promptly inform the reviewing IRB/REB/EC.  Medtronic will provide a written statement to the investigators 
to enable prompt notification of the IRB/REB/EC.  If trial enrollment is terminated early, follow-up visits will 
continue for all implanted subjects. 
15.9.2 
Suspension or Early Termination of a Trial Site 
Medtronic may decide to suspend or prematurely terminate an investigation site (e.g. in case of expiring 
approval of the reviewing IRB/REB/EC, non-compliance to the CIP, or lack of enrollment).  If an investigation 
site 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 IRB/REB/EC. 
16 Other Institutions and Professional Services 
This study will utilize an Echo Core Lab, ECG Core Lab, a Pathology Core Lab, an angiogram Core Lab, a 
membranous septum Core Lab, Steering Committee, Screening Committee, and a Clinical Events 
Committee.  Information and contact details for each of these parties will be maintained in a separate 
document and provided to the study sites.  A definitive list of all participating parties will be provided in 
clinical reports.  In addition, a list of the names and addresses of participating institutions will be 
maintained and provided to the sites upon request. 
 
17 References 
1. Popma JJ, Adams DH, Reardon MJ et al. Transcatheter aortic valve replacement using a self-
expanding bioprosthesis in patients with severe aortic stenosis at extreme risk for surgery. J Am Coll 
Cardiol 2014;63:1972-81. 
2. Adams DH, Popma JJ, Reardon MJ et al. Transcatheter aortic-valve replacement with a self-
expanding prosthesis. N Engl J Med 2014;370:1790-8. 
3. Reardon MJ, Van Mieghem NM, Popma JJ et al. Surgical or Transcatheter Aortic-Valve Replacement 
in Intermediate-Risk Patients. N Engl J Med 2017;376:1321-1331. 

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4. Forrest JK, Mangi AA, Popma JJ et al. Early Outcomes With the Evolut PRO Repositionable Self-
Expanding Transcatheter Aortic Valve With Pericardial Wrap. JACC Cardiovasc Interv 2018;11:160-168. 
5. Lauck SB, Wood DA, Achtem L et al. Risk stratification and clinical pathways to optimize length of 
stay after transcatheter aortic valve replacement. Can J Cardiol 2014;30:1583-7. 
6. Lauck SB, Wood DA, Baumbusch J et al. Vancouver Transcatheter Aortic Valve Replacement Clinical 
Pathway: Minimalist Approach, Standardized Care, and Discharge Criteria to Reduce Length of Stay. 
Circ Cardiovasc Qual Outcomes 2016;9:312-21. 
7. van Rosendael PJ, Delgado V, Bax JJ. Pacemaker implantation rate after transcatheter aortic valve 
implantation with early and new-generation devices: a systematic review. Eur Heart J 2018;39:2003-
2013. 
8. Brignole M, Auricchio A, Baron-Esquivias G et al. 2013 ESC Guidelines on cardiac pacing and cardiac 
resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the 
European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm 
Association (EHRA). Eur Heart J 2013;34:2281-329. 
9. Sharma E, Chu AF. Predictors of right ventricular pacing and pacemaker dependence in 
transcatheter aortic valve replacement patients. J Interv Card Electrophysiol 2018;51:77-86. 
10. 
Auffret V, Puri R, Urena M et al. Conduction Disturbances After Transcatheter Aortic Valve 
Replacement: Current Status and Future Perspectives. Circulation 2017;136:1049-1069. 
11. 
Urena M, Mok M, Serra V et al. Predictive factors and long-term clinical consequences of 
persistent left bundle branch block following transcatheter aortic valve implantation with a balloon-
expandable valve. J Am Coll Cardiol 2012;60:1743-52. 
12. 
Gilard M ea. Registry of Transcatheter Aortic-Valve Implantation in High-Risk Patients. New 
England Journal of Medicine 2012:1705-1715. 
13. 
Nishimura RA, Otto CM, Bonow RO et al. 2014 AHA/ACC guideline for the management of 
patients with valvular heart disease: Executive summary :A report of the american college of 
cardiology/american heart association task force on practice guidelines. Circulation 2014;129:2440-
2492. 
14. 
Webb JG, Wood DA. Current status of transcatheter aortic valve replacement. Journal of 
the American College of Cardiology 2012;60:483-92. 
15. 
Genereux P, Head SJ, Wood DA et al. Transcatheter aortic valve implantation: 10-year 
anniversary part II: clinical implications. European heart journal 2012;33:2399-402. 

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16. 
Buellesfeld L, Gerckens U, Schuler G et al. 2-year follow-up of patients undergoing 
transcatheter aortic valve implantation using a self-expanding valve prosthesis. Journal of the 
American College of Cardiology 2011;57:1650-7. 
17. 
Ussia GP, Barbanti M, Petronio AS et al. Transcatheter aortic valve implantation: 3-year 
outcomes of self-expanding CoreValve prosthesis. European heart journal 2012;33:969-76. 
18. 
Dubois D, Dubois, E.F. A formula to estimate the approximate surface area if height and 
weight be known. Arch Intern Medicine 1916;17:863-71. 
19. 
Baumgartner H, Hung J, Bermejo J et al. Echocardiographic assessment of valve stenosis: 
EAE/ASE recommendations for clinical practice. European journal of echocardiography : the journal of 
the Working Group on Echocardiography of the European Society of Cardiology 2009;10:1-25. 
20. 
Douglas PS, Waugh RA, Bloomfield G et al. Implementation of echocardiography core 
laboratory best practices: a case study of the PARTNER I trial. Journal of the American Society of 
Echocardiography : official publication of the American Society of Echocardiography 2013;26:348-358 
e3. 
21. 
Clavel MA, Rodes-Cabau J, Dumont E et al. Validation and characterization of transcatheter 
aortic valve effective orifice area measured by Doppler echocardiography. JACC Cardiovascular 
imaging 2011;4:1053-62. 
22. 
Shames S, Koczo A, Hahn R, Jin Z, Picard MH, Gillam LD. Flow characteristics of the SAPIEN 
aortic valve: the importance of recognizing in-stent flow acceleration for the echocardiographic 
assessment of valve function. Journal of the American Society of Echocardiography : official 
publication of the American Society of Echocardiography 2012;25:603-9. 
23. 
Miller FA, Jr. Echocardiography derived valve area of the Edwards SAPIEN aortic valve 
prosthesis: new methodology is required to comply with old hemodynamic principles. Journal of the 
American Society of Echocardiography : official publication of the American Society of 
Echocardiography 2012;25:610-2. 
24. 
Genereux P, Head SJ, Hahn R et al. Paravalvular leak after transcatheter aortic valve 
replacement: the new Achilles' heel? A comprehensive review of the literature. Journal of the 
American College of Cardiology 2013;61:1125-36. 
25. 
Pibarot P, Hahn RT, Weissman NJ, Monaghan MJ. Assessment of paravalvular regurgitation 
following TAVR: a proposal of unifying grading scheme. JACC Cardiovascular imaging 2015;8:340-60. 
26. 
Zoghbi WA, Enriquez-Sarano M, Foster E et al. Recommendations for evaluation of the 
severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. Journal 

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of the American Society of Echocardiography : official publication of the American Society of 
Echocardiography 2003;16:777-802. 
27. 
Lang RM, Bierig M, Devereux RB et al. Recommendations for chamber quantification: a 
report from the American Society of Echocardiography's Guidelines and Standards Committee and the 
Chamber Quantification Writing Group, developed in conjunction with the European Association of 
Echocardiography, a branch of the European Society of Cardiology. Journal of the American Society of 
Echocardiography : official publication of the American Society of Echocardiography 2005;18:1440-63. 
28. 
Nagueh SF, Appleton CP, Gillebert TC et al. Recommendations for the evaluation of left 
ventricular diastolic function by echocardiography. Journal of the American Society of 
Echocardiography : official publication of the American Society of Echocardiography 2009;22:107-33. 
29. 
Zamorano JL, Badano LP, Bruce C et al. EAE/ASE recommendations for the use of 
echocardiography in new transcatheter interventions for valvular heart disease. Journal of the 
American Society of Echocardiography : official publication of the American Society of 
Echocardiography 2011;24:937-65. 
18 Appendices 
18.1 Conduction Disturbance Management 
The following section is intended to provide consistency in the management of subject’s conduction 
disturbance peri and post the TAVR index procedure.   
All subjects are required to have 12-lead ECG within the 2 hours following the TAVR procedure and the day 
of discharge.  The 2-hour post procedure ECG, peri-procedural rhythm abnormalities, and pre-existing 
conduction abnormalities will determine the pathway.  
 
Subjects with pre-existing conduction disturbances (eg RBBB) or new conduction disturbances may be 
discharged prior to the recommended timeframes with continuous ECG monitoring. Pacing wires may be 
removed prior to recommended timeframe and telemetry may be discontinued prior to the recommended 
timeframe to allow for early discharge. 
 
No ECG Changes Immediately (2 Hours) Post Procedure: 
• 
No new ECG changes refers specifically to PR and QRS increase < 20 ms on the ≤ 2-hour post-op 
ECG compared to the pre-procedure ECG. 
• 
Subjects Without Pre-Existing RBBB: 
o Temporary pacing wires can be removed within 2 hours of the TAVR index procedure with 
continuous telemetry for 24 hours post-op.   

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o If there are no new changes between the ECG done 24 hours post-op compared to the 2-
hour post-op ECG done, then the subject is eligible to be discharged 1-day post op.   
o Proceed with pacemaker implantation if there is an occurrence of HAVB/CHB any time 
during the post-TAVR period.  
• 
Subjects With Pre-Existing RBBB: 
o Maintain temporary pacing until after 24 hours post the TAVR index procedure.   
o If there are no changes between the ≤ 2-hour post-op ECG compared to the 24-hour post-
op ECG, then the temporary pacing wire can be removed.  Continue telemetry for 1  day 
and if there continues to be no new ECG changes then the subject is eligible to be 
discharged 2 days post index procedure 
o If there are ECG changes of at least ≥ 20 ms in the PR or QRS duration compared to the ECG 
2-hour post-op, then refer to instructions for New ECG Changes.  
o Proceed with pacemaker implantation if there is an occurrence of HAVB/CHB any time 
during the post-TAVR period.  
 
 ECG Changes (Increase of PR or QRS ≥ 20 ms) in patients with pre-existing conduction disturbance: 
• 
If there are ECG changes of ≥ 20 m/s in the PR or QRS duration on the ≤ 2-hour post op ECG 
compared to the ECG done pre-procedure, and subjects have pre-existing RBBB, LBBB, IVCD with 
QRS ≥ 120 ms or 1st degree AVB pre-procedure, then temporary pacing must be maintained until 24 
hours post the TAVR index procedure.  
o If ECG changes resolve (regression to baseline value, irrespective of QRS/PR interval 
duration), OR there are no further changes between the ≤ 2-hour post-op ECG compared to 
the 24-hour post-op ECG and QRS ≤ 150 ms and PR ≤ 240 ms, then the temporary pacing 
wire can be removed.  Continue telemetry for 1 day. If there are no further ECG changes 
and/or bradyarrythmias, the subject is eligible to be discharged 2 days post index 
procedure. 
o  If there are ECG changes of ≥ 20 ms in the PR or QRS duration OR the QRS > 150 ms or PR > 
240 ms, then maintain temporary pacing for an additional 24 hours.   
 
If ECG changes resolve (regression to baseline value, irrespective of QRS/PR interval 
duration), OR no further ECG changes and QRS ≤ 150 ms and PR ≤ 240 ms then 
temporary pacing wire can be removed; continue telemetry for 1 day. If there are 
no further ECG changes and/or bradyarrythmias, the subject is eligible to be 
discharged 2 days post index procedure. 
 
If there are no further ECG changes, but QRS >150 ms or PR >240 ms OR further 
ECG changes of ≥20 ms in the PR or QRS duration consider one of the following:  
• 
Invasive EP study to guide the decision about pacemaker implantation 
• 
Continuous ECG monitoring until the 30-day follow-up visit. 
• 
Pacemaker implantation (not in patients with PR >240 ms but QRS <120 
ms)  

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o Proceed with pacemaker implantation if there is an occurrence of HAVB/CHB any time 
during the post-TAVR period.  
 
New Onset LBBB Post Procedure: 
• 
Maintain temporary pacing until after 24 hours post the TAVR index procedure.   
o If there are no changes between the ≤ 2-hour post-op ECG compared to the 24-hour post-
op ECG or the LBBB is resolved, then the temporary pacing wire can be removed and 
continue telemetry for 1 day: 
 
If there continues to be no new ECG changes or arrythmias and the LBBB resolves, 
then the subject is eligible to be discharged 2 days post index procedure without 
continuous monitoring. 
 
If the LBBB continues and QRS ≤ 150 ms and PR ≤ 240 ms compared to the 24-hour 
post-op ECG then the subject must be discharged with a continuous ECG 
monitoring system; which could occur as soon as 2 days post index procedure.  The 
subject should maintain the continuous ECG monitoring system until the 30-day 
follow-up visit.   
 
If the LBBB continues and QRS > 150 ms or PR > 240 ms then consider one of the 
following:  
• 
Invasive EP study to guide the decision about pacemaker implantation 
• 
Continuous ECG monitoring until the 30-day follow-up visit 
• 
Pacemaker implantation 
o If there are further ECG changes of at least ≥ 20 ms in the PR or QRS duration between the 
2-hour post-op ECG compared to the 24-hour post-op ECG, then maintain temporary 
pacing for an additional 24 hours.   
 
If no further ECG changes compared to 24-hour ECG (PR or QRS increase < 20 ms)or 
LBBB is resolved, then refer to instruction noted above.   
 
If the ECG changes do not resolve and there is further ≥ 20 ms changes in the PR or 
QRS duration, then consider one of the following:  
• 
Invasive EP study to guide the decision about pacemaker implantation 
• 
Continuous ECG monitoring until the 30-day follow-up visit 
• 
Pacemaker implantation 
o Proceed with pacemaker implantation if there is an occurrence of HAVB/CHB any time 
during the post-TAVR period.  
 
HAVB/CHB (transient or persistent) during the TAVR procedure: 
• 
Maintain temporary pacing until after 24 hours post the TAVR index procedure. 

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1 year 
Day 365 ± 30 days 
18.3.2 
General Imaging and Recording Procedures 
• 
A list of recommended images is provided in Section 19.3.3, List of Recommended Images. 
• 
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 any CD-R disks sent to the Echo Core Lab: 
- Trial site ID number 
- Subject ID number 
- Exam date 
- Trial interval 
 
18.3.3 
List of Recommended Images 
Parasternal long-axis window 
1. 2D gray scale standard view (LV in a sagittal section) 
2. 2D color Doppler for mitral regurgitation (MR) 
3. 2D color Doppler of aortic (native or prosthetic) regurgitation (AR) 
4. If AR is present, ZOOM & narrow sector with focus on vena contracta of regurgitant jet  
5. 2D gray scale ZOOM for LV outflow tract diameter (LVOT)  
6. Frozen image of measured LVOT diameter 

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7. 2D gray scale; ZOOM at an intercostal space higher for aortic root/aortic prosthesis  
Parasternal short-axis window 
8. 2D grayscale LV at mitral valve level 
9. 2D grayscale LV at papillary muscle level  
10. Frozen image of measured LV dimensions (without measurements) 
11. 2D grayscale LV at apical level 
12. 2D grayscale aortic valve level 
13. 2D color Doppler of AR: post-implant 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) 
14. 2D color Doppler of tricuspid regurgitation (TR) 
15. If TR is present, CW Doppler of TR jet (frozen image without measurements) 
16. Frozen image of TR jet velocity with measurements 
Apical 4-Chamber window 
17. 2D grayscale standard view  
18. 2D color Doppler of MR  
19. If MR is present, ZOOM & narrow sector 
20. If MR is present, CW Doppler of MR jet (frozen image) 
21. 2D color Doppler of TR 
22. If TR is present, CW Doppler of TR jet (frozen image without measurement) 
23. Frozen image of TR jet velocity with measurements 
24. 2D grayscale focussed on LV with decreased depth 
25. PW Doppler of transmitral flow at mitral valve tips (frozen image) 
26. Tissue Doppler of the septal mitral annulus (frozen image) 
27. Tissue Doppler of the lateral mitral annulus (frozen image) 
Apical long–axis view 
28. 2D grayscale standard view 
29. 2D color Doppler of AR 
30. If AR is present, ZOOM & narrow sector, shift Nyquist 35-40 for PISA measurements  
31. If AR is present, CW Doppler of AR jet (frozen image without measurement) 
32. Frozen image of CW Doppler of AR jet (with measurements) 
33. CW Doppler of aortic/prosthetic valve (frozen image without measurement) 
34. Frozen image of measured aortic/prosthetic valve velocity 

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35. PW Doppler LVOT (native aortic valve): within 0.5 – 1 cm below native aortic valve (frozen image 
without measurements 
36. PW Doppler LVOT (post –implant) immediately proximal to inflow of stent or valve (frozen image 
without measurements) 
37. Frozen image: measured LVOT velocity 
Apical 2-Chamber view 
38. 2D grayscale standard view 
39. 2D grayscale focused on LV with decreased depth 
Sub-costal Position 
40. 2D grayscale; long-axis view 
41. 2D grayscale; short-axis view 
42. 2D grayscale: IVC and hepatic vein 
43. If TR moderate by color Doppler, PW Doppler of hepatic vein (frozen image) 
44. IF AR mild by color Doppler, PW Doppler from descending aorta (frozen image) 
Supra-Sternal Position 
45. CW Doppler of aortic valve velocity non-imaging probe (frozen image without measurements) 
46. Frozen image: measured aortic valve velocity 
47. If AR mild by color Doppler, PW Doppler from descending aorta (frozen image) 
Right Parasternal Position 
48. CW Doppler of aortic valve velocity; non-imaging probe (frozen image without measurements) 
49. Frozen image: measured aortic valve velocity 
Results Reporting 
50. Screen prints of all results pages 
 
18.3.4 
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 19.3.5, 
Acquisition of Key Variables. 
• 
Height (cm) and Weight (kg) 
• 
Heart rate 
• 
Left ventricular outflow tract (LVOT) diameter in mid systole 
• 
Max aortic/prosthetic valve velocity (V 2) by CW Doppler 
• 
Aortic valve velocity time integral (VTI) by CW Doppler 
• 
Mean gradient across aortic valve (MGV 2) by CW Doppler 

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• 
LVOT VTI by PW Doppler 
• 
Grade of aortic/prosthetic transvalvular regurgitation (post-implant only) 
• 
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 
• 
Grade of diastolic dysfunction (if present) 
 
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)(18) 
• 
Peak aortic pressure gradient 
• 
Aortic valve area (AVA)/effective orifice area (EOA) by continuity equation 
• 
Aortic valve area/effective orifice area index (EOAI) 
• 
Doppler Velocity Index 
• 
Estimated right ventricular systolic pressure (RVSP) 
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. 
18.3.5 
Acquisition of Key Variables 
18.3.5.1 
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 2 A and B).(19,20). Following implantation of the TAV, LVOT 
diameter is measured from the parasternal long-axis view, immediately proximal to the inflow aspect of the 
stent, and in mid systole (Figure 2 C and D) (19-21) Post-surgical valve implantation, LVOT diameter is 

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measured from the junction of the anterior sewing ring and the ventricular septum to the junction of the 
sewing ring and the anterior mitral valve leaflet (Figure 2 E and F).(19)  
 
 
Figure 2 (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 TAV implantation, LVOT 
diameter measurement is from outer edge to outer edge of the inflow aspect of the stent (E) and (F) post surgical 
valve implantation, LVOT diameter is measured from the junction of the anterior sewing ring and the ventricular 
septum to the junction of the sewing ring and the anterior mitral valve leaflet. 
 

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18.3.5.2 
LVOT Velocity 
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 3).(19) 
Post TAV implantation, the sample volume should be placed proximal to the inflow aspect of the stent.(22) 
Full-screen imaging of the TAV should be used to verify positioning of the sample volume below the stent 
before switching to spectral Doppler mode (Figure 3 C and D).(22,23) 
The LVOT VTI is measured by tracing the modal velocity (middle of the dense signal) for use in the 
continuity equation.(19) 
            
 
Figure 3 (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 
TAV stent (D) Full-screen imaging of stent to ensure positioning of sample volume below the TAV stent. 
 
 

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18.3.5.3 
Aortic Valve Velocities 
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 4).(19) 
 
Figure 4 (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. 
 
18.3.5.4 
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.(24,25) 
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 6.(25) 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 6.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 semiquantitative) 
 
 
 
 
 
 
 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 
Often present 
Usually present 
Usually 
present 
   Proximal flow convergence 
visible 
Absent 
Absent 
Absent 
Possible 
Often present 
Often 
present 
 Vena contracta width (mm) 
<2 
<2 
2-4 
4-5 
5-6 
>6 
 Vena contracta area (mm2) 
<5 
5-10 
10-20 
20-30 
30-40 
>40 
 Jet width at origin (% LVOT 
diameter) 
Narrow (<5) 
Narrow (5-
15) 
Intermediate 
(15-30) 
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 
Intermediate 
Holodiastolic 
(end-diast. Vel. 
>20 cm/s) 
Holodiastolic 
(end-diast. 

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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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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 
18.3.5.7 
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 5). Left 
ventricular chamber dimensions, septal thickness, and posterior wall thickness are measured using the 
American Society of Echocardiography (ASE) measurement convention(27) (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 5. Measurements of the left ventricle (A) and left atrium (B) using 2-D guided m-mode. 
 
18.3.5.8 
Assessment of Left Ventricular Diastolic Function 
A spectral Doppler recording of mitral inflow should be obtained with PW Doppler in the apical 4-
chamber view, using a 1 to 3 mm sample volume placed between the mitral leaflet tips during diastole 
(Figure 6). The spectral gain and wall filter settings should be optimized to clearly display the onset and 
cessation of left ventricular inflow. The following variables should be measured: 
• 
Mitral inflow “A” velocity 
• 
Mitral inflow “E” velocity 
• 
Mitral inflow E-wave deceleration time 
 
A 
B 

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Figure 6. Positioning of the sample volume for recording of mitral inflow velocities. 
 
Mitral annular velocities should be obtained from the lateral and septal aspects of the mitral annulus 
using PW tissue Doppler (DTI) performed in the apical 4-chamber view. The sample volume should be 
positioned at or 1 cm within the septal and lateral insertion sites of the mitral leaflets and adjusted as 
necessary (usually 5 to 10 mm) to cover the longitudinal excursion of the mitral annulus in both systole 
and diastole. Minimal angulation (<20 degrees) should be present between the ultrasound beam and 
the plane of cardiac motion. The following variables should be measured: 
• 
Mitral annular tissue Doppler systolic velocity (septal and lateral) 
• 
Mitral annular tissue Doppler early diastolic velocity (septal and lateral) 
• 
Mitral annular tissue Doppler late diastolic velocity (septal and lateral) 
18.3.6 
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 trial.  
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 (V 2) by CW Doppler 

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• 
Aortic valve velocity time integral (VTI) by CW Doppler 
• 
Mean gradient across aortic valve (MGV 2) by CW Doppler 
• 
LVOT VTI by PW Doppler 
• 
Grade of aortic/prosthetic transvalvular regurgitation (post-implant only) 
• 
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 
• 
Grade of diastolic dysfunction (if present) 
• 
Diastolic function should be categorized as normal, mild dysfunction (impaired relaxation 
pattern), moderate dysfunction (pseudonormal filling), or severe dysfunction (restrictive filling) 
per the 2009 American Society of Echocardiography recommendations.(28) 
 
Qualitative grading of valvular regurgitation will be performed using the criteria described in Sections 
19.3.5.4 through 19.3.4.8. 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. (26,29) 
 
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 (V 2 2) 
Where: V 2 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 (VTI V1/VTI V2) 
Where: VTI V1 is the velocity time integral of the left ventricular outflow tract in cm, and VTI V2 is 
the velocity time integral of the native aortic valve in cm 
 
• Aortic Valve Area Index (AVAI) in cm2/m2 

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AVAI = AVA/BSA* 
Where: AVA is the native aortic valve area in cm2, and BSA* is the body surface area in m2 1 
 
• Effective Orifice Area (EOA) in cm2 
EOA = LVOT diameter2 x 0.785 x (VTI V1/VTI V2) 
Where: VTI V1 is the velocity time integral of the left ventricular outflow tract in cm, and VTI V2 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= VTI V1/VTI V2 
Where: VTI V1 is the velocity time integral of the left ventricular outflow tract in cm, and VTI V2 is 
the time velocity integral of the prosthetic aortic valve in cm 
 
• Left Ventricular Mass (LVM) in grams 
LVM = 0.83 x [(LVIDD + LVPW + IVS)3 - (LVIDD)3] +0.6 
Where: LVIDD is the left ventricular internal dimension at end diastole in cm, LVPW is the left 
ventricular posterior wall thickness at end diastole in cm, and IVS is the interventricular wall 
thickness at end diastole in cm. 
 
• Left Ventricular Mass Index (LVMI) in g/m2 body surface area 
LVMI = LVM/BSA* 
Where: LVM is left ventricular mass in g, and BSA* is body surface area in m2 
 
• 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) 
 
* BSA derived from height and weight reported on the site eCRF  
 
18.4  Recommended MSCT Procedures 
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 
 
* BSA derived from height and weight reported on the site eCRF 

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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. 
 
18.4.2.2 
Required aortic root measurements 
The following measurements of the aortic root are obtained for assessing anatomical suitability: 
• 
Aortic valve annulus perimeter (measured at systole if retrospective gating is used) 
• 
Mean sinus of Valsalva diameter (measured at diastole) 
• 
Mean sinus of Valsalva heights (measured at diastole) 
 
Reformatting of Images (21) 
• 
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 7., upper left panel). 
• 
In the sagittal window, the horizontal line is rotated clockwise or counter-clockwise to align 
with virtual basal plane (Figure 7, 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 8).  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. 
• 
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. 
 

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Figure 8. 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). 
 
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. 
• 
Trace the perimeter of the basal annulus (Figure 9, 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 9, right). 
 
 
  
 
Figure 9.  Example of perimeter measurement (left) and major and minor diameter measurements (right). 
 
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 “Reformatting of Images.” 
Sinus of Valsalva diameters 
• 
Select the double oblique axial image where the widest portion of the three sinuses is visible. 
• 
Measure a diameter from each commissure through the site of the root to the opposite 
sinus. Complete for all three sinuses (Figure 10). 

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Figure 30.  Example of sinus of Valsalva diameters 
 
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 11). 

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Ventricular septal 
perforation 
Angiographic or echocardiographic evidence of a new septal perforation during 
or after the TAVR 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 Evolut™ PRO or PRO+) of the mitral valve during or after the TAVR 
procedure 
Cardiac tamponade 
Evidence of new pericardial effusion associated with hemodynamic instability 
and clearly related to the TAVR procedure 
Valve Thrombosis 
(Clinical) 
Any thrombus not caused by infection attached to or near the trial valve that 
occludes part of the blood flow path, interferes with valve function, or is 
sufficiently large to warrant treatment which is associated with any of the 
following clinical sequelae.: 
• 
Thromboembolic complications including 
o Any ischemic stroke  
o Any peripheral embolic event  
o ST segment elevation or Non-ST elevation myocardial 
infarction 
• 
Hemodynamic impairment associated with a worsening of heart failure 
Note: valve thrombus found at autopsy in a subject whose cause of death was 
not valve-related or found at operation for an unrelated indication should not 
be reported as valve thrombosis 
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 

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regurgitation). 
Valve migration 
After initial correct positioning, any observed movement (upward or 
downward) of the Evolut™ PRO or PRO+ within the aortic annulus from its initial 
position, with or without consequences. 
Valve embolization 
The Evolut™ PRO or PRO+ moves during  or after deployment such that it loses 
contact within the aortic annulus* 
Ectopic valve 
deployment 
Permanent deployment of the Evolut™ PRO or PRO+  in a location other than 
the aortic root 
Valve in Valve 
deployment 
Additional valve prosthesis is implanted within a previously implanted Evolut™ 
PRO or 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). 
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 
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. 
Aborted procedures will be considered serious adverse events regardless of 
reason for termination of the procedure.   
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 

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o Roll-in subjects will complete in-clinical follow-up 
evaluations as noted in section 9.1.5 Follow-Up 
Evaluations however the results for the roll-in 
population will be analyzed separately from the 
primary analysis cohorts. 
• 
Heart Team: added language stating the Heart Team 
should assess eligibility of the subject according to the 
site’s standard process and payer requirements. 
• 
Trial Organization: updated Publication Committee 
members to include steering committee members 
• 
Inclusion/Exclusion Criteria: Added exclusion criteria: 
o Subjects with pre-existing permanent pacemaker 
o Previous aortic valve replacement 
o Exclude subjects with horizontal aorta (aortic 
angulation > 70 degrees per the IFU) 
o Prohibitive left ventricular outflow tract 
calcification 
• 
Implant Procedure: Added statement in introduction of 
section. 
o In addition, the valve deployment will be 
completed in accordance to the cusp overlap 
technique via procedural angiography. 
• 
Follow-Up Evaluations: Added procedural angiography 
during TAVR procedure in Summary of Visit Schedule and 
Required Evaluations table. 
• 
Adverse Events and Definitions:  
o Added in AE definition table: “Ballooning as 
needed during the implant procedure is standard 
practice and should not be considered a 
reintervention.” 
o Clarified that Serious Adverse Events and Device 
Deficiencies will be collected from the time of 
enrollment 
• 
Statistical Design and Methods: Added potential for 
interim analysis in Primary Analysis.  
• 
Sample size:  
o Updated rationale for sample size 
o Updated sample size to include roll-in subjects 
• 
Conduction Disturbance Management Appendix: Updates 
to introduction section 
o Removed statement: An occurrence or recurrence 
of high-degree atrioventricular block (HAVB) or 
third-degree atrioventricular block (complete 
heart block [CHB]) (see definitions of conduction 

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disturbances section) at any time between 
procedure and discharge is an indication for 
permanent pacemaker implantation (PPI) (refer to 
HAVB during the TAVR procedure section). 
o Removed reference to subjects with pre-existing 
pacemakers.   
o Added statement: Subjects with pre-existing 
conduction disturbances (eg RBBB) or new 
conduction disturbances may be discharged prior 
to the recommended timeframes with continuous 
ECG monitoring. Pacing wires may be removed 
prior to recommended timeframe and telemetry 
may be discontinued prior to the recommended 
timeframe to allow for early discharge. 
o Revised instruction for the following cohorts: 
 
ECG changes (48 hours post op QRS 
remains > 150 ms, PR remains > 240 ms, 
or further increase of ≥ 20 ms PR 
compared to 24-hour post-op ECG) and  
 
New LBBB (48 hours post op continuing 
QRS > 150 ms or PR > 240 ms): 
 
Revised instruction: consider EP study to 
further evaluate if the subject should be 
implanted with a permanent pacemaker 
or discharge with continuous ECG 
monitoring system until 30-day follow-up 
visit. 
• 
Endpoint Definitions: Clarified valve thrombus found at 
autopsy in a subject whose cause of death was not valve-
related or found at operation for an unrelated indication 
should not be reported as valve thrombosis.   
 
4.0 
• 
Added the Evolut PRO+ 23, 26, 29, and 34mm TAVs, DCSs, 
and LSs to the commercially available devices able to be used 
in the study 
• 
Added guidewires and sheaths to the device list in the 
Synopsis 
• 
Added requirement to report non-serious VARC-2 adverse 
events from the time of enrollment until the completion of 
follow-up 
• 
Section 8.2.2 Updated to say the Training and Education 
Committee will provide recommendations for transition of 
 
  

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• 
Up to 15 sites with at least 200 subjects 
• 
Increased enrollment period to 36 months and study 
duration to 4 years 
• 
Updated inclusion criterion #1 to say: Acceptable candidate 
for treatment with the Evolut™ PRO or Evolut™ PRO+ system 
in accordance with the commercial Instructions for Use and 
local regulations 
• 
Removed exclusion criteria: Any percutaneous coronary or 
peripheral interventional procedure performed within 30 
days prior to enrollment 
• 
Added Section 6.2 Study Oversight 
• 
Section 7: removed EnVeo R Delivery System and Loading 
System since they are no longer being used in the 
geographies part of this study 
• 
Section 7.1.1: added European/Israeli device model numbers 
to Table 2 and Table 3 
• 
Section 9.2.1: Included that Medtronic will provide 
correspondence to sites when they are approved to move 
into the as-treated analysis phase 
• 
Section 9.3: changed word from “randomization” to 
“participation” 
• 
Section 10.1. 2: Updated duration from enrollment to TAVR 
procedure from 30 days to 90 days 
• 
Section 10.1.5: Added clarification in Table 4 on when ECGs 
must be collected within the study and removed statement 
regarding collection of UB-04 billing statements 
• 
Section 12.1: updated SAE and Device Deficiency definition to 
be current and added Serious Adverse Device Effect and 
Unanticipated Serious Adverse Device Effect definitions. In 
addition, added language on assessing SAE relatedness 
• 
Added Section 12.4: Product Complaint Reporting 
• 
Section 13.3: Included pacemaker implantation analysis 
required by BSI and referenced the TAVR Low Risk Post 
Market Clinical Follow-Up Plan 
• 
Section 13.1.1: updated the Per Protocol sets (1 and 2) 
• 
Section 14: Added that EU centers will follow EU MDR and 
GDPR 

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• 
Section 16: Added angiogram Core Lab and membranous 
septum Core Lab 
• 
Section 18.1: Clarified when a subject is required to be 
discharged with continuous ECG monitoring if they are in the 
new onset LBBB group 
• 
Section 18.3.1: Updated echo requirement to say one needs 
to be done within 10 weeks prior to procedure as this was an 
error in the previous CIP version 
• 
Section 18.4.3: added valve size information for the PRO+ 
34mm TAV and Minimal Lumen Diameter information for all 
valve sizes 
6.0 
• 
Added “EU Legal Representative” to the Bakken Research 
Center for local sponsor 
• 
Added ANZ as a local sponsor 
• 
Local Sponsor: Changed Canada address to ULC from LTD. 
• 
Added up to 7 sites in Australia and New Zealand with 
approximately 50 subjects 
• 
Updated overall sponsor to “Medtronic Structural Heart 
Clinical Research” and removed “Coronary” 
• 
Updated references to tables throughout document for 
accuracy 
• 
Changed ‘as treated’ to ‘attempted implant’ in sections 9.2.1 
and 13.1 to align with the statistical analysis set 
• 
Section 2: added ANZ (Australia, New Zealand) and VARC 
(Valve Academic Research Consortium) to the glossary 
• 
Added roll-in Sample Size to the Study Synopsis 
• 
Section 3 & Section 5: Updated Primary Objective to Study 
Objective and updated language to say: The study objective is 
to collect post-market clinical evidence on valve performance 
and procedural outcomes associated with an “optimized” 
TAVR care pathway and post-TAVR conduction disturbance 
pathway while using the Evolut™ PRO and Evolut™ PRO+ 
devices. In addition, added primary, secondary, and 
exploratory objectives to align with the primary, secondary, 
and exploratory endpoints 
• 
Section 7.1.1: Corrected the US Model Numbers for the DCS 
and LS as they were previously listed incorrectly. Added 
Australia, New Zealand, & Israeli Model Numbers for all 
devices 
 

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• 
Section 9.2: added additional 50 patients and 7 sites in ANZ. 
Stated study will include approximately 650 subjects instead 
of ‘up to 650 subjects’  
• 
Section 10.1.3.1: Added all steps included in the cusp-overlap 
procedural technique 
• 
Section 10.2: Updated language to say that new information 
would be provided to subjects in an updated informed 
consent 
• 
Section 10.6.1: Added definition of source data 
• 
Section 12.1: Added definition of Adverse Event and Adverse 
Device Effect 
• 
Section 13.1.1: removed ‘s’ from “Roll-ins subjects” in the 
“Roll-in” description 
• 
Section 13.1.1: Clarified the primary analysis will be based off 
the endpoints, not the objectives 
• 
Section 13.3:   
o Removed language stating another interim 
analysis will occur after 400 subjects are enrolled 
in the attempted implant set.  
o Modified language to state that pacemaker 
implantation rates at 30 days will be compared by 
region (US/CAN, EMEA, and ANZ). 
• 
Section 13.4:  
o Added additional 50 patients and 7 sites in ANZ to 
make the entire study population 854 (including 
roll-ins) 
o Removed the words “up to” from the total 
combined sample size with all analysis sets is 854 
subjects 
• 
Section 14.1:  
o Updated to say the study will comply to ICH E6 R2 
GCP 
o Clarified that each site must fulfill all local 
regulatory requirements prior to enrolling 
subjects and throughout the duration of the 
study, as applicable and updated regulations for 
Europe. 

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• 
Section 15.6: Added language that Medtronic will maintain 
a list of internal CIP approvers separate from this 
document. 
• 
Section 18.6:  
o Added Evolut PRO+ throughout where applicable 
with Evolut PRO 
o Removed the table with Signs and Symptoms of 
Aortic Valve Disease and added a new table that 
has the definition for Hospitalization and 
Rehospitalization