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: 21Jul2019 

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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 
Sponsor/Local Sponsor Medtronic, Inc. 
Coronary and Structural Heart Clinical  
 
 
 
  
 
 
 
 
 
 
Medtronic of Canada Ltd. 
 
  
 
 
 
 
Document Version 3.0, 21 July 2019 
Co-Principal Investigators Dr. Kendra Grubb 
Emory University Hospital 
 
 
 
Dr. Steven Yakubov 
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 
Sponsor 
Medtronic Coronary and Structural Heart Clinical  
Version Number/Date  
3.0, 21 July 2019 
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.................................................................................................................... 2 
Table of Contents ................................................................................................................................... 3 
2. 
Glossary .......................................................................................................................................... 7 
3. 
Synopsis ......................................................................................................................................... 9 
4. 
Introduction.................................................................................................................................. 11 
4.1. Background and Rationale ................................................................................................................... 11 
4.2. Purpose ................................................................................................................................................ 12 
5. 
Objectives and Endpoints .............................................................................................................. 12 
5.1. Objectives ............................................................................................................................................ 12 
5.1.1. 
Primary Objective ....................................................................................................................... 12 
5.2. Endpoints ............................................................................................................................................. 12 
5.2.1. 
Primary Endpoint ........................................................................................................................ 12 
5.2.2. 
Secondary Endpoints .................................................................................................................. 12 
5.2.3. 
Additional Exploratory Endpoints ............................................................................................... 12 
5.2.4. 
Rationale ..................................................................................................................................... 13 
6. 
Study Design ................................................................................................................................. 13 
6.1. Duration ............................................................................................................................................... 13 
6.2. Trial Organization ................................................................................................................................ 13 
6.2.1 
Participating Sites ....................................................................................................................... 13 
6.2.2. 
Site Principal Investigator ........................................................................................................... 14 
6.2.2 
Heart Team ................................................................................................................................. 14 
6.2.3 
Publication Committee ............................................................................................................... 14 
6.2.4 
Trial Training ............................................................................................................................... 15 
7. 
Product Description ...................................................................................................................... 15 
7.1 Description of Devices ......................................................................................................................... 15 
7.1.2 Medtronic Evolut PRO System ......................................................................................................... 15 
7.2. Manufacturer ....................................................................................................................................... 19 
7.3. Intended Population ............................................................................................................................ 19 

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7.4. Product Training Requirements ........................................................................................................... 20 
7.5. Product Labeling, Tracking, and Accountability .................................................................................. 20 
7.6. Product Storage ................................................................................................................................... 20 
8. 
Selection of Subjects ..................................................................................................................... 20 
8.1 Study Population ................................................................................................................................. 20 
8.2. Subject Enrollment .............................................................................................................................. 20 
8.3. Inclusion Criteria .................................................................................................................................. 21 
8.4. Exclusion Criteria ................................................................................................................................. 21 
9. 
Study Procedures .......................................................................................................................... 22 
9.1 Schedule of Events ............................................................................................................................... 22 
9.1.1 
Screening Procedures ................................................................................................................. 23 
9.1.2 
Enrollment .................................................................................................................................. 23 
9.1.3 
Implant Procedure (TAVR) .......................................................................................................... 24 
9.1.4 
Prior to Discharge ....................................................................................................................... 25 
9.1.5 
Follow-Up Evaluations ................................................................................................................ 25 
9.1.6 
Additional Evaluations for Pacemaker Implants ......................................................................... 27 
9.1.7 
Missed Follow-Up Visits .............................................................................................................. 27 
9.1.8 
Core Labs ..................................................................................................................................... 27 
9.1.9 
Informed Consent ....................................................................................................................... 27 
9.2 Revisions in Patient Information and Informed Consent Form ........................................................... 28 
9.3 Assessment of Efficacy ........................................................................................................................ 28 
9.4 Assessment of Safety ........................................................................................................................... 29 
9.4.1 
Serious Adverse Events and Device Deficiencies ........................................................................ 29 
9.5 Recording Data .................................................................................................................................... 29 
9.5.1 
Source Documents ...................................................................................................................... 29 
9.6 Deviation Handling .............................................................................................................................. 30 
9.7 Subject Withdrawal or Discontinuation .............................................................................................. 31 
10 Risks and Benefits ......................................................................................................................... 31 
10.1 Potential Risks...................................................................................................................................... 31 

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10.2 Potential Benefits ................................................................................................................................ 31 
10.3 Risk-Benefit Rationale ......................................................................................................................... 32 
10.3.1 
Measures to Mitigate Risks in the Trial Subjects .................................................................... 32 
10.3.2 
Alternatives ............................................................................................................................. 32 
10.3.3 
Results from the Risk Analysis and Justification for the Study ............................................... 32 
11 Adverse Events and Device Deficiencies ......................................................................................... 33 
11.1 Definitions/Classifications ................................................................................................................... 33 
11.1.1 
Evaluation and Documentation of Serious Adverse Events .................................................... 33 
11.1.2 
Evaluation and Documentation of Device Deficiencies .......................................................... 35 
11.2 Reporting of Serious Adverse Events .................................................................................................. 35 
11.3 Emergency Contact Details for Reporting SAE and Device Deficiencies ............................................. 35 
12 Data Review Committees .............................................................................................................. 35 
12.1 Clinical Events Committee ................................................................................................................... 35 
13. Statistical Design and Methods ...................................................................................................... 36 
13.1 Analysis Populations ............................................................................................................................ 36 
13.1.1 
Enrolled Population ................................................................................................................. 36 
13.2 Description of Baseline Variables ........................................................................................................ 36 
13.3 Primary Analysis .................................................................................................................................. 37 
13.3.1 
Primary Endpoint .................................................................................................................... 37 
13.4 Sample Size .......................................................................................................................................... 37 
13.5 Secondary Endpoints ........................................................................................................................... 37 
13.6 Additional Exploratory Endpoints ........................................................................................................ 37 
13.7 Missing Data ........................................................................................................................................ 38 
14. Ethics and Regulatory Compliance ................................................................................................. 38 
15. Study Administration .................................................................................................................... 39 
15.1. 
Monitoring ..................................................................................................................................... 39 
15.2. 
Data Management ......................................................................................................................... 39 
15.3. 
Direct Access to Source Data/Documents ..................................................................................... 40 
15.4. 
Confidentiality ............................................................................................................................... 40 

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15.5. 
Liability .......................................................................................................................................... 40 
15.6. 
CIP Amendments ........................................................................................................................... 40 
15.7. 
Record Retention ........................................................................................................................... 41 
15.8. 
Publication and Use of Information .............................................................................................. 41 
15.9. 
Suspension or Early Termination ................................................................................................... 41 
15.9.1 
Suspension or Early Termination of the Trial .......................................................................... 41 
15.9.2 
Suspension or Early Termination of a Trial Site ...................................................................... 41 
16. Other Institutions and Professional Services .................................................................................. 42 
17. Version History ............................................................................................................................. 42 
18. References .................................................................................................................................... 45 
19. Appendices ................................................................................................................................... 47 
19.1 Conduction Disturbance Management ............................................................................................... 47 
19.2 Quality of Life Questionnaires ............................................................................................................. 51 
19.3 Echocardiography Procedure .............................................................................................................. 51 
19.3.1 
Required Exams ....................................................................................................................... 51 
19.3.2 
General Imaging and Recording Procedures ........................................................................... 51 
19.3.3 
List of Recommended Images ................................................................................................. 52 
19.3.4 
Data Requirements ................................................................................................................. 54 
19.3.5 
Acquisition of Key Variables .................................................................................................... 55 
19.3.6 
Core Lab Analysis ..................................................................................................................... 64 
19.4 Recommended MSCT Procedures ....................................................................................................... 66 
19.4.1 
General requirements ............................................................................................................. 67 
19.4.2 
ECG-gated contrast enhanced scan of aortic root .................................................................. 67 
19.4.3 
Anatomic suitability and valve size selection .......................................................................... 72 
19.5 Resheath and Recapture Definitions ................................................................................................... 72 
19.6 Endpoint Definitions ............................................................................................................................ 73 
 
 
 

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• 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 system in 
accordance with the Instructions for Use  
• 
Anatomically not suitable for the Evolut™ PRO system; 
• 
Any percutaneous coronary or peripheral interventional procedure 
performed within 30 days prior to enrollment; 
• 
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; 

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• 
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 
• 12-lead ECG at pre and post-procedure, 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 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 valve’s outer pericardial wrap has shown to enhance annular sealing 
resulting in 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 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 pacemakers 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 and a pre-specified TAVR care 
pathway.  Additionally, this study will protocolize the management of the post-TAVR conduction 

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disturbances and evaluate whether a consistent deployment technique will reduce the variability of new 
onset conduction disturbances.   
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 device. 
5. Objectives and Endpoints 
5.1. Objectives 
5.1.1. 
Primary Objective 
The primary objective 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 device. 
5.2. Endpoints 
The following endpoints will be used to evaluate the primary trial objectives: 
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 
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 

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5.2.4. 
Rationale 
The basis for the selection of these study endpoints include: 
• 
Clinically relevant outcomes of the Evolut PRO device 
• 
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 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 less than 12 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 less than 2 years.  
6.2. Trial Organization 
6.2.1 
Participating Sites 
This trial may be conducted at up to 46 sites in the United States and Canada.  Investigative sites will meet 
the following criteria: 
• 
The site will have extensive facility experience with TAVR.  Operator 1 and Operator 2 must 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: 

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o Minimum of 2 TAVR implanters with expertise in transcatheter aortic valve replacement as 
noted above 
o Electrophysiologist  
o Echocardiographer 
o Trial coordinator 
 
6.2.2. 
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 requirements. 
6.2.2 
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. 
6.2.3 
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.   

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EnVeo R LS 
LS-MDT2-23-US 
LS-MDT2-23 
Used with 23 
mm TAV 
Not applicable 
LS-MDT2-2629-US 
LS-MDT2-2629 
Used with 26 
and 29 mm TAV 
Not applicable 
EnVeo PRO LS 
L-ENVPRO-1623US 
L-ENVPRO-1623 
Used with 23 
mm TAV 
Not applicable 
L-ENVPRO-16-US 
L-ENVPRO-16 
Used with 26 
and 29 mm TAV 
Not applicable 
 
 

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Figure 1. (A) Evolut PRO TAV; (B) EnVeo PRO DCS and EnVeo InLine Sheath; (C) EnVeo R DCS and EnVeo InLine Sheath 
(D) EnVeo R LS (E) EnVeo PRO 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 bioprotheses: 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. 
7.1.2.2 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. 

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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, the device packaging is swiveled 
and secured to facilitate the bioprosthesis loading procedure. 
7.1.2.3 Medtronic EnVeo R Catheter Delivery System with EnVeo InLine 
Sheath 
The EnVeo R catheter delivery system 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. 
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 EnVeo InLine Sheath for the 23 mm, 
26 mm, and 29 mm Evolut PRO system is compatible with a 20 Fr introducer.  
The delivery catheter system consists of a catheter with an integrated handle to provide the user with 
accurate and controlled deployment. The handle is on the proximal end of the catheter and is used to load, 
deploy, recapture, and reposition the bioprosthesis. The handle features a gray front grip used to stabilize 
the system. The blue actuator turns to deploy the bioprosthesis precisely. Arrows on the actuator indicate 
the direction of rotation required to deploy the bioprosthesis. If desired, the blue actuator can be turned in 
the opposite direction to recapture the bioprosthesis if the radiopaque capsule marker band has not yet 
reached the distal end of the spindle. The blue actuator also features a trigger, which can be engaged to 
make macro adjustments to the capsule position. A blue hand rest connects to the blue actuator. The end 
of the handle features a tip-retrieval mechanism, which can be used to withdraw the catheter tip to meet 
the capsule after the device has been fully deployed. 
The catheter packaging contains an integrated loading bath and a removable tray with 3 rinsing bowls for 
loading and rinsing the bioprosthesis. The integrated loading bath features a mirror, which aids in accurate 
placement of the bioprosthesis frame paddles during loading. In addition, the device packaging is swiveled 
and secured to facilitate the bioprosthesis loading procedure. 

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7.4. Product Training Requirements 
The Evolut PRO device will be used within the local approved indication, with exception to any 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, handling, return of these devices will be followed.   
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.   
In Canada, only system components licensed for sale by Health Canada will be used in the study.   
7.6. Product Storage 
Sites will follow their institutional standard practice for storing commercial TAVR product. 
8. 
Selection of Subjects 
8.1 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 system in accordance with 
Instructions for Use and local regulations. 
8.2. Subject Enrollment 
This study will involve up to 400 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.   
8.2.2. 
Roll-In Subjects 
For all participating centers, the first three subjects implantedwill be considered “roll-in” subjects.  The 
purpose of the roll-in subjects is to provide Investigators the time for training and familiarization with the 

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protocolized implant technique.  The Training and Education team will review recommendations made by 
the Steering Committee for transition of sites from roll-in phase to as treated analysis phase.   
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.  
8.3. Inclusion Criteria 
Prospective subjects must meet all of the following inclusion criteria to be eligible for randomization: 
1. Acceptable candidate for treatment with the Evolut PRO system in accordance with the 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. 
8.4. 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 system in accordance with the Instructions for 
Use  
2. Anatomically not suitable for the Evolut PRO system; 
3. Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior 
to enrollment; 
4. Reduced ventricular function with left ventricular ejection fraction (LVEF) < 35% as measured by 
resting echocardiogram; 
5. Previous aortic valve replacement; 
6. 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) 

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 
Body Mass Index <20kg/m2 
 
Grip strength <16kg 
 
Katz Index score ≤4 
 
Albumin <3.5 g/dL 
7. Bicuspid valve verified; 
8. Aortic root angulation (angle between plane of aortic valve annulus and horizontal 
plane/vertebrae) > 70°.   
9. Implanted with pacemaker or ICD; 
10.  Prohibitive left ventricular outflow tract calcification; 
11. Estimated life expectancy of less than 12 months due to associated non-cardiac co-morbid 
conditions; 
12. 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; 
13. Currently participating in an investigational drug or another device trial (excluding registries); 
14. Need for emergency surgery for any reason. 
15. 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) 
9. 
Study Procedures  
9.1 Schedule of Events 
Follow-up protocol required evaluations should be performed at the trial site.  The protocol required 
evaluations for each trial interval are listed as follows and summarized in Table 2. 

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9.1.1 
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 
• 
MDCT angiogram – within 1 year prior to procedure 
• 
TTE – within 10 weeks prior to procedure 
• 
Heart Team eligibility assessment 
• 
12-lead ECG – within 48 hours prior to procedure  
• 
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.   
9.1.2 
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 
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 30 days post-enrollment. 

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9.1.3 
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: 
• 
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  
• 
No planned general anesthesia  
• 
Percutaneous and transfemoral femoral 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 
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 19.1 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 

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9.1.4 
Prior to Discharge  
• 
Physical examination and concomitant medications. 
• 
NYHA classification 
• 
12-lead ECG (refer to Appendix 19.1 Conduction Disturbance Management for discharge 12-lead ECG 
requirements for subjects with conduction abnormalities) 
• 
Laboratory tests - glomerular filtration rate (GFR), hemoglobin, international normalized ratio (INR) for 
subjects on warfarin, and serum creatinine  
• 
TTE – must be done within 12 hours and 7 days post TAVR  
• 
Adverse event review 
9.1.5 
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 height, 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 height, 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 pacemakers post index TAVR procedure 
• 
Adverse event review 
 

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9.1.6 
Additional Evaluations for Pacemaker Implants 
Medtronic brand pacemakers are required to be implanted for subjects that require pacemaker 
implantation post the TAVR index procedure through the duration of their study participation in order to 
collect device data from pacemakers.  Device data will be collected remotely via CareLink™ system at 3, 6, 
and 9 months post pacemaker implantation and during in-office pacemaker interrogations at pacemaker 
implant, 30-day, and 12-month follow-up visit. 
For subjects that require pacemaker implantation, a final ‘Interrogate All’ device interrogation file must be 
obtained and saved in a digital format (Save-to-Media) at pacemaker implant, 30 day, and 12-month 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).  
9.1.7 
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. 
9.1.8 
Core Labs  
Transthoracic echocardiography (TTE), ECGs, angiogram imaging, and external Holter monitor data (for 
applicable subjects) will be sent to core labs for central assessment.  Further details of the 
echocardiography methods are provided in Appendix 19.3. 
9.1.9 
Informed 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 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 and by Medtronic, Inc.  All 
Informed Consent Forms, including HIPAA forms 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 

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the consent.  Any additional persons required by the site’s IRB/REB 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.  
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, MDCT, 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. 
9.2 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 by the IRB/REB.   
9.3 Assessment of Efficacy 
The following methods will be used for assessing, recording, and analyzing efficacy.  Refer to section 9.1 
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 

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9.4 Assessment of Safety 
9.4.1 
Serious Adverse Events and Device Deficiencies  
Serious adverse events and device deficiencies will be collected from the time of enrollment until the end 
of the study or until study exit, whichever comes first.   
9.5 Recording Data 
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 user name 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. 
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. 
9.5.1 
Source Documents 
Entered data must be traceable to 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 

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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, MDCT 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 FDA and other applicable regulatory agencies or IRB/REB.   
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. 
9.6 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 approval before the start of the study 
• 
Implanted subject did not meet inclusion/exclusion criteria 
• 
Enrollment of subjects during lapse of IRB/REB 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 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 

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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. 
9.7 Subject 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. 
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.  
10  Risks and Benefits 
10.1 Potential Risks 
There are possible risks and side effects connected to the Evolut PRO TAV implant, but the risks are the 
same as  those for an implant of the Evolut PRO TAV without participation in this study. Standard risks 
associated with the Evolut PRO system in the study are provided in the Instruction for Use. 
Risks and events will be continuously monitored, assessed and documented by the investigator. 
10.2 Potential Benefits 
Participation in this clinical study will not result in any direct benefit to the patient. Trial subjects implanted 
with an Evolut PRO receive the same medical treatment as if they were not participating in this post-market 

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study. Participation contributes to expansion the knowledge base with respect to the use of the Evolut PRO 
system in a routine hospital setting. 
10.3 Risk-Benefit Rationale 
10.3.1 
Measures to Mitigate Risks in the Trial Subjects 
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 
10.3.2 
Alternatives 
Presently, therapeutic alternatives for patients with the clinical indication targeted for the Medtronic TAVR 
System include the following: 
• 
Medical therapy 
• 
Balloon aortic valvuloplasty 
• 
Surgical aortic valve replacement 
• 
TAVR with a non-Medtronic system 
10.3.3 
Results from the Risk Analysis and Justification for the Study 
TAVR is now established as a safe and effective treatment option for patients with symptomatic severe 
aortic stenosis who are at extreme, high, or intermediated risk for surgical aortic valve replacement. The 
Medtronic CoreValve™ system, the Evolut R system, and the Evolut PRO system (referred jointly as 
Medtronic TAVR) has been in widespread use since receiving the CE Mark in 2007, and there is now 
extensive published experience demonstrating the Medtronic TAVR system is fulfilling its intended role with 
a favorable risk/benefit ratio.(14-17) Rigorous clinical trials have established its safety and effectiveness, with 
improved mortality and quality of life compared with medical therapy in extreme , high and intermediate 
risk patients. (1-4)  
There are risks to the subjects for participation in the trial, they are anticipated to be to the same as risks 
provided in the IFU and guideline compatible therapy outside of the context of the study (i.e. TAVR or SAVR 
in a commercial, non-study setting).   

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The CEC members will be free from bias towards the trial and will be independent from both the trial and 
investigators and Medtronic.  The committee will consist of at least 3 independent experts (non-Medtronic 
employed physicians) with expertise relevant to the trial.  This may include experience in the areas of: 
• 
Cardiac surgery 
• 
Interventional cardiology 
• 
Neurology 
• 
Electrophysiology 
13. Statistical Design and Methods 
13.1 
Analysis Populations 
13.1.1 Enrolled Population 
Within the enrolled population the following analysis sets are distinguished: 
• 
The as treated (AT) set: The AT 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 AT 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 set: The per protocol set consists of all implanted subjects who’s index procedure adhere 
to the TAVR care pathway as described in section 9.1.3 Implant Procedure TAVR (treated with conscious 
sedation, iliofemoral, no concomitant procedures, etc.) 
• 
Roll-in: Roll-ins subjects will not be analyzed with the AT, implanted, or per protocol set and will be 
analyzed separately using descriptive statistics.  
The primary analysis for the primary objective and secondary safety and effectiveness objectives will use 
the as treated set.   
13.2 
Description of Baseline Variables 
Baseline demographic and clinical variables will be summarized for the AT, 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.   

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13.3 
Primary Analysis 
The study objective and endpoints are descriptive, and no statistical hypothesis testing will be performed.  
Interim analyses will be conducted after 100 subjects are enrolled in the AT 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.   
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 AT population is 400 subjects and up to 46 sites in the US and Canada. The sample 
size for the roll-in population is up to 138 subjects. Total combined sample size with all analysis populations 
is up to 538 subjects.  
This is not a hypothesis-driven study, therefore the sample size of up to 400 subjects was not determined 
by statistical sample size methods. With >25% of TAVR patients experiencing new conduction 
disturbances10, 400 patients will provide a sufficient sample (~100 patients) to evaluate the conduction 
disturbance management pathway.  
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 

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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. 
The reasons for missing data will be described and evaluated for assessment of possible bias.  The 
distribution of prognostic factors between subjects with data and those without data will be examined to 
evaluate any potential sources of bias. 
14. Ethics and Regulatory Compliance 
This study will be conducted in accordance to the Evolut PRO commercially approved IFU and therefore is 
not considered to be a high risk study.  An Investigational Device Exemption (IDE) is not required to be 
submitted to the FDA and a pre-approval submission is not required to be submitted to Health Canada, if 
appropriate.   
The study will be conducted in accordance with the protocol, GCP, and ethical principles that have their 
origin in the Declaration of Helsinki. Each site must fulfill all local regulatory requirements prior to enrolling 
subjects, as applicable. 
Participating sites will be not be activated nor begin enrolling subjects until the required approval/favorable 
opinion from the local IRB/REB 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 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 approved Health Insurance Portability and Accountability Act (HIPAA) 
Authorization, when applicable. 
IRB/REB 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 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. If they are members of the IRB/REB, 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 approval once the investigation site has started 
enrollment.  If any action is taken by an IRB/REB with respect to the study, that information will be 
forwarded to Medtronic by the respective investigator. 

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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 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.  
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.  

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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 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 if required. 
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.  The investigator will only implement the 
amendment after approval of the IRB/REB, and Medtronic.  Administrative amendments to the CIP will be 
submitted to the IRB/REB for notification.  Furthermore, investigators shall sign any approved amendment 
for agreement. 

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15.7. Record Retention 
At a minimum, the investigator must retain records for at least 2 years 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. 
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. 
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.  Medtronic will, as soon as possible, provide a written statement to 
the investigators to enable prompt notification of the IRB/REB.  If trial enrollment is terminated early, 
follow-up visits will continue for all enrolled 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, 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 

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for transition of sites from roll-in phase to as treated 
analysis phase.   
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:  

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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 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.   
 

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18. 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. 
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. 
International Standard ISO 14155:2011(E).  Clinical investigation of medical devices for human 
subjects - Good Clinical Practice. 
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 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. 

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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. 
 
19. Appendices  
19.1 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.   
o If there are no new changes between the ECG done 24 hours post-op compared to the 2-
hour post-op ECG done (PR or QRS increase ≥ 20 ms), then the subject is eligible to be 
discharged 1-day post op.  This will also apply to those patients with normal ECG pre-TAVR 
and PR or QRS changes not reaching the criteria for 1st degree AVB and QRS <120 ms.  Refer 
to instructions for ECG changes if PR or QRS ≥ 20 m/s in patients with a) prior conduction 
abnormalities and b) with normal ECG pre-TAVR and ECG changes reaching the criteria for 
1st degree AVB or QRS interval duration >120 m/s. 
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.   

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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 – 2 
days and if there continues to be no new ECG changes then the subject is eligible to be 
discharged 2 – 3 days post index procedure with a continuous ECG monitoring via a Holter 
monitor.  The subject should maintain the continuous ECG monitoring system until the 30-
day follow-up visit.   
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): 
• 
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 m/s or 1st degree AVB pre-procedure, then temporary pacing must be maintained until 
after 24 hours post the TAVR index procedure.  
o If ECG changes resolve, or there are no further changes of ≥ 20 ms between the ≤ 2-hour 
post-op ECG compared to the 24-hour post-op ECG and QRS ≤ 150 m/s and PR ≤ 240 m/s, 
then the temporary pacing wire can be removed.  Continue telemetry for 1- 2 days. If there 
are no further ECG changes and/or bradyarrythmias, the subject is eligible to be discharged 
2 – 3 days post index procedure with a continuous ECG monitoring via a long-term Holter 
monitor until the 30-day follow-up visit. 
o  If there are ECG changes of ≥ 20 ms in the PR or QRS duration OR the QRS > 150 m/s or PR 
> 240 ms, then maintain temporary pacing for an additional 24 hours.   
 
If ECG changes resolve, or no further ECG changes and QRS ≤ 150 ms and PR ≤ 240 
ms then temporary pacing wire can be removed; continue telemetry for 1- 2 days. 
If there are no further ECG changes and/or bradyarrythmias, the subject is eligible 
to be discharged 2 – 3 days post index procedure with a continuous ECG monitoring 
via a long-term Holter monitor until the 30-day follow-up visit. 
 
Permanent pacemaker implantation may be considered if at 48 hours post-op the 
QRS remains > 150 m/s, PR remains > 240 m/s, or further increase of ≥ 20 m/s PR 
compared to 24-hour post-op ECG. 
• 
An EP study may be used to further evaluate the need for pacemaker 
implantation.   Infra-Hisian block during atrial pacing or a spontaneous HV 
interval > 100 ms should prompt permanent pacemaker implantation. 
• 
In those patients with 1st degree atrioventricular block (with stable PR 
duration for at least 24 hours, irrespective of PR interval duration) as the 
only conduction abnormality and a QRS duration <120 ms, continuous ECG 
monitoring at hospital discharge via a Holter monitor is preferred instead 
of permanent pacemaker. The subject should maintain the continuous ECG 
monitoring system until the 30-day follow-up visit.     

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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 – 2 days: 
 
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 is eligible to be discharged 2 – 3 days post index 
procedure with a continuous ECG monitoring via a Holter monitor.  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 proceeding 
with pacemaker implantation or an EP study to further evaluate if the subject 
should be implanted with a permanent pacemaker.   Infra-Hisian block during atrial 
pacing or a spontaneous HV interval > 100 ms should prompt permanent 
pacemaker implantation. 
o If there are 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 in the PR or QRS 
duration, then proceed with implanting a permanent pacemaker.  
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. 
o If the subject continues to experience HAVB/CHB then proceed with implanting a 
permanent pacemaker.     
o If the HAVB/CHB resolves and there is not recurrent heart block, then the temporary pacing 
wire can be removed and continue telemetry for 1-2 days.   
 
If the HAVB/CHB reoccurs then proceed with implanting a permanent pacemaker.   

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• 
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 
 
19.3.3 
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 
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) 

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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 
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 

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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 
 
19.3.4 
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 (V2) by CW Doppler 
• 
Aortic valve velocity time integral (VTI) by CW Doppler 
• 
Mean gradient across aortic valve (MGV2) by CW Doppler 
• 
LVOT VTI by PW Doppler 
• 
Grade of aortic/prosthetic transvalvular regurgitation (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 

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• 
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. 
19.3.5 
Acquisition of Key Variables 
19.3.5.1 
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 
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)  

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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. 
 
19.3.5.2 
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 

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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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19.3.5.3 
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. 
 
19.3.5.4 
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 5.(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 5.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 
19.3.5.7 
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. 
 
19.3.5.8 
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) 
19.3.6 
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 (V2) by CW Doppler 

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• 
Aortic valve velocity time integral (VTI) by CW Doppler 
• 
Mean gradient across aortic valve (MGV2) by CW Doppler 
• 
LVOT VTI by PW Doppler 
• 
Grade of aortic/prosthetic transvalvular regurgitation (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 (V22) 
Where: V2 is the peak velocity across the prosthesis in m/sec 
 
• Aortic Valve Area (AVA) in cm2 
AVA = LVOT diameter in cm2 x 0.785 x (VTIV1/VTIV2) 
Where: VTIV1 is the velocity time integral of the left ventricular outflow tract in cm, and VTIV2 is 
the velocity time integral of the native aortic valve in cm 
 
• Aortic Valve Area Index (AVAI) in cm2/m2 

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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 m21 
 
• Effective Orifice Area (EOA) in cm2 
EOA = LVOT diameter2 x 0.785 x (VTIV1/VTIV2) 
Where: VTIV1 is the velocity time integral of the left ventricular outflow tract in cm, and VTIV2 is 
the velocity time integral of the aortic prosthesis in cm 
 
• Effective Orifice Area Index (EOAI) in cm2/m2 
EOAI = EOA/BSA* 
Where: EOA is the effective orifice area in cm2, and BSA* is the body surface area in m2 
 
• Doppler Velocity Index (DVI) 
DVI= VTIV1/VTIV2 
Where: VTIV1 is the velocity time integral of the left ventricular outflow tract in cm, and VTIV2 is 
the time velocity integral of the prosthetic aortic valve in cm 
 
• 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  
 
19.4  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. 
 
19.4.2.2 
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 20.  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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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 
regurgitation). 
Valve migration 
After initial correct positioning, any observed movement (upward or 
downward) of the Evolut™ PRO within the aortic annulus from its initial 
position, with or without consequences. 
Valve embolization 
The Evolut™ PRO moves during  or after deployment such that it loses contact 
within the aortic annulus* 
Ectopic valve 
deployment 
Permanent deployment of the Evolut™ PRO in a location other than the aortic 
root 
Valve in Valve 
deployment 
Additional valve prosthesis is implanted within a previously implanted Evolut™ 
PRO because of sub-optimal device position and/or function, during or after the 
index procedure. 
Hemolysis 
Red cell destruction as evidenced by plasma free hemoglobin >50 mg/dl 
Minor hemolysis: No intervention required 

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Stenosis: mild 
For subjects with BSA ≥ 1.6 m2: Mean aortic gradient ≥ 20 and ≤40 
mmHg, EOA ≥ 0.8 and ≤ 1.1 cm2 AND/OR DVI ≥ 0.25 and ≤ 0.35 
For subjects with BSA < 1.6 m2: Mean aortic gradient ≥ 20 and 
≤40 mmHg, EOA ≥ 0.6 cm2 and ≤ 0.9 cm2 AND/OR DVI ≥ 0.25 and 
≤ 0.35 
Stenosis: moderate/severe 
For subjects with BSA ≥ 1.6 m2: Mean aortic gradient > 40 mmHg, EOA 
< 0.8 cm2 AND/OR DVI < 0.25 
For subjects with BSA < 1.6 m2: Mean aortic gradient > 40 mmHg, EOA 
< 0.6 cm2 AND/OR DVI < 0.25 
Paravalvular 
regurgitation: moderate 
Moderate paravalvular regurgitation (per echo criteria in CIP) 
Paravalvular 
regurgitation: severe 
Severe paravalvular regurgitation (per echo criteria in CIP) 
Transvalvular 
regurgitation: moderate 
Moderate transvalvular regurgitation (per echo criteria in CIP) 
Transvalvular 
regurgitation: severe 
Severe transvalvular regurgitation (per echo criteria in CIP) 
Notes: 
• 
DVI = Doppler Velocity Index (LVOT VTI/valve VTI) 
• 
For subjects LVOT diameter > 2.5 cm, the DVI criteria for significant (moderate or severe) stenosis 
is 0.2 
• 
Reporting of prosthetic valve dysfunction will be based on core lab values (if available). 
• 
Prosthetic valve dysfunction events are not reported as adverse events, unless the dysfunction is 
accompanied with clinical sequelae at the time of event detection, and the clinical sequelae are 
chronologically and physiologically associated with the dysfunction. However, prosthetic 
dysfunctions that are associated with adverse events, and that meet the definition of a serious 
adverse event, should be reported as such.