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: 15Dec2022 

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Clinical Investigation Plan Addendum 
Clinical Investigation Plan/Addendum 
Title  
Optimize PRO TAVR Post Market Study – FX Addendum 
Study Product Name Medtronic Evolut™ FX System 
Sponsor/Local Sponsor  
Medtronic, Inc. 
Structural Heart Clinical  
 
 
  
 
Document Version 3.0, 15 December 2022 
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 Agreement and Signature Page 
Study product Name 
Medtronic Evolut™ FX System 
Sponsor 
Medtronic Structural Heart Clinical  
Version Number/Date  
3.0, 15 December 2022 
 
I have read the Optimize PRO Clinical Investigation Plan – FX Addendum 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 Optimize PRO Study 
Protocol, Optimize PRO – FX Addendum, 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 addendum 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 addendum. 
 
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 ..................................................................................................................................... 7 
4. 
Introduction ............................................................................................................................... 9 
4.1. Parent Study ...................................................................................................................................... 9 
4.2. Purpose ............................................................................................................................................. 9 
5. 
Objective and Endpoints ........................................................................................................... 10 
5.1. Objective ......................................................................................................................................... 10 
5.2. Endpoints ........................................................................................................................................ 10 
5.2.1. 
Primary Endpoint .................................................................................................................. 10 
5.2.2. 
Secondary Endpoints ............................................................................................................. 10 
5.2.3. 
Additional Exploratory Endpoints ......................................................................................... 10 
5.2.4. 
Rationale ............................................................................................................................... 10 
6. 
Study Design ............................................................................................................................ 11 
6.1. Duration .......................................................................................................................................... 11 
6.2. Study Oversight ............................................................................................................................... 11 
6.3. Trial Organization ............................................................................................................................ 11 
7 
Product Description .................................................................................................................. 11 
7.1 Description of Devices .................................................................................................................... 11 
7.1.1 Medtronic Evolut FX System ...................................................................................................... 12 
7.2 Manufacturer .................................................................................................................................... 14 
7.3 Intended Population ......................................................................................................................... 14 
7.4 Product Training Requirements ........................................................................................................ 15 
7.5 Product Labeling, Tracking, and Accountability ................................................................................ 15 
7.6 Product Storage ................................................................................................................................ 15 
8 Study Site Requirements ............................................................................................................... 15 
8.1 FX Addendum Site Activation ......................................................................................................... 15 

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9 Selection of Subjects ..................................................................................................................... 16 
9.1 Study Population ............................................................................................................................. 16 
9.2 Subject Enrollment ............................................................................................................................ 16 
9.3 Inclusion Criteria ............................................................................................................................... 16 
9.4 Exclusion Criteria ............................................................................................................................... 16 
10 Study Procedures ........................................................................................................................ 18 
10.1 Schedule of Events .......................................................................................................................... 18 
10.1.1 
Screening and Enrollment Procedures .............................................................................. 18 
10.1.2 
Implant Procedure (TAVR) and peri-procedural data collection ....................................... 18 
10.1.2.1 
External ECG Monitors ...................................................................................................... 19 
10.1.3 
Follow-Up Evaluations ....................................................................................................... 19 
10.1.3.1 
Visit Windows .................................................................................................................... 19 
10.1.4 
Additional Evaluations for Pacemaker Implants................................................................ 20 
10.1.5 
Missed Follow-Up Visits ..................................................................................................... 21 
10.1.6 
Core Labs ........................................................................................................................... 21 
10.1.7 
Subject Consent ................................................................................................................. 21 
10.2 Assessment of Efficacy .................................................................................................................... 21 
10.3 Assessment of Safety ...................................................................................................................... 21 
10.4 Device Malfunction or Explant ........................................................................................................ 21 
10.5 Data Collection ................................................................................................................................ 21 
10.5.1 
Source Documents ............................................................................................................. 21 
10.6 Deviation Handling .......................................................................................................................... 21 
10.7 Subject Exit, Withdrawal or Discontinuation .................................................................................. 22 
11 Risks and Benefits ....................................................................................................................... 22 
11.1 Potential Risks ................................................................................................................................. 22 
11.2 Potential Benefits ............................................................................................................................ 22 
11.3 Risk-Benefit Rationale ..................................................................................................................... 22 
12 Adverse Events and Device Deficiencies ....................................................................................... 22 
12.1 Emergency Contact Details for Reporting AEs and Device Deficiencies ......................................... 22 

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13 Statistical Design and Methods .................................................................................................... 23 
13.1 General Aspects of Analysis ............................................................................................................ 23 
13.1.1 
Enrolled Population ........................................................................................................... 23 
13.2 Description of Baseline Variables ................................................................................................... 23 
13.3 Primary Analysis .............................................................................................................................. 24 
13.3.1 
Primary Endpoint ............................................................................................................... 24 
13.4 Sample Size ..................................................................................................................................... 24 
13.5 Secondary Endpoints ...................................................................................................................... 24 
13.6 Additional Exploratory Endpoints ................................................................................................... 24 
13.7 Missing Data .................................................................................................................................... 25 
14 Ethics .......................................................................................................................................... 25 
14.1 Statement of Compliance ............................................................................................................... 25 
15 Study Administration ................................................................................................................... 25 
15.1. 
Monitoring ................................................................................................................................ 25 
15.2. 
Data Management .................................................................................................................... 25 
15.3. 
Direct Access to Source Data/Documents ................................................................................ 25 
15.4. 
Confidentiality ........................................................................................................................... 25 
15.5. 
Liability ...................................................................................................................................... 25 
15.6. 
CIP Amendments ...................................................................................................................... 25 
15.7. 
Record Retention ...................................................................................................................... 25 
15.8. 
Publication and Use of Information .......................................................................................... 26 
15.9. 
Suspension or Early Termination .............................................................................................. 26 
16 Other Institutions and Professional Services ................................................................................. 26 
17 References .................................................................................................................................. 26 
18 Appendices ................................................................................................................................. 26 
18.1 Appendix I: Post-Procedure MSCT Requirements .......................................................................... 26 
18.1.1 
General Requirements ....................................................................................................... 26 
18.1.2 
ECG-gated Contrast Enhanced Scan of Aortic Root ........................................................... 27 
18.1.3 
Post-processing .................................................................................................................. 27 

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19 Version History ......................................................................................................................... 28 
 
 
 

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2. Glossary 
Refer to the Optimize PRO parent protocol for a glossary of terms. 
3. Synopsis 
Title 
Optimize PRO – FX Addendum 
Devices 
Medtronic Evolut™ FX TAV System  
Sponsor  
Medtronic Structural Heart Clinical Research  
FX Addendum Principal 
Investigator 
Dr. Hemal Gada 
Product Status 
Only commercially approved product will be used. 
Study Objective 
The purpose of this addendum is to collect post-market clinical 
evidence on valve performance and procedural outcomes associated 
with the Evolut FX Device. 
Primary Endpoint 
Rate of all-cause mortality or all-stroke at 30 days 
Secondary Endpoints 
• Median days from index procedure to discharge 
• Percentage of subjects with ≥ moderate aortic regurgitation (AR) at 
discharge 
• Rate of pacemaker implant for new onset or worsening conduction 
disturbance at 30 days  
• Percentage of subjects with a Non-Coronary Cusp (NCC) depth of 
implant between 1.0 and 5.0 mm 
• Percentage of subjects with a canting absolute value |NCC − Left 
Coronary Cusp (LCC)| of ≤ 2.0 mm 
Additional Exploratory 
Endpoints 
• 30-day and 1-year hospital re-admission rates 
• 1-year composite of all-cause mortality or all-stroke 
• Percent of patients with a major vascular complication 
• Percent of patients that require a recapture or resheath of the TAV 
• Percent of patients in which the target depth of implant was 
achieved 
• Orientation of valve relative to native anatomy 
Study Design 
Post-market, multi-center, prospective, non-randomized 
Sample Size 
Approximately 10 sites in the United States with approximately 150 
subjects  

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Patient Population 
Subjects with severe, symptomatic aortic stenosis (AS) necessitating 
valve replacement 
Duration 
Total addendum duration is estimated to be 24 months (time from 
first subject implanted to one-year follow-up on last subject 
implanted) 
Key Inclusion Criteria 
• Acceptable candidate for treatment with the Evolut FX system in 
accordance with the Instructions for Use and local regulations 
• Subject is symptomatic from his/her aortic valve stenosis, as 
demonstrated by New York Heart Association (NYHA) Functional 
Class II or greater 
• Subject and the treating physician agree that the subject will 
return for all required post procedure follow-up visits 
• Anatomically suitable for transfemoral TAVR with the Medtronic 
TAVR system 
• Subject meets the legal minimum age to provide Informed Consent 
based on local regulatory requirements 
Key Exclusion Criteria 
• 
Contraindicated for treatment with the Evolut™ FX system in 
accordance with the Instructions for Use 
• 
Anatomically not suitable for the Evolut™ FX system 
• 
Previous aortic valve replacement 
• 
Reduced ventricular function with left ventricular ejection 
fraction (LVEF) < 35% as measured by resting echocardiogram 
• 
Frailty assessments identify: 
o Subject is <80 years of age and three or more of the 
following apply; OR subject is > 80 years of age and 
two or more of the following apply  
 
Wheelchair bound 
 
Resides in an institutional care facility (e.g., 
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 

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• 
Estimated life expectancy of less than 12 months due to 
associated non-cardiac co-morbid conditions 
• 
Other medical, social, or psychological conditions that in the 
opinion of the Investigator precludes the subject from 
appropriate consent, adherence to the protocol required follow-
up exams 
• 
Currently participating in an investigational drug or another 
device trial (excluding registries) 
• 
Need for emergency surgery for any reason 
• 
Subject is less than legal age of consent, legally incompetent, or 
otherwise vulnerable 
Study Procedures and 
Assessments 
• Clinical assessment at baseline, discharge, 30 days, and 1 year 
• Transthoracic echo at baseline, discharge, and 1 year  
• Multi-Detector Computed Tomography at baseline and anytime 
post-procedure through the 30-day visit (contrast required for 
post-procedure CT) 
• Quality of Life pre- and post-procedure, 30 days, and 1 year 
• 12-lead ECG at pre- and post-procedure, discharge, 30 days, and 1 
year 
4. Introduction  
4.1. Parent Study 
The Optimize PRO Clinical Investigation Plan (Parent protocol or Parent CIP) is the governing document 
for this addendum.  Always refer to the most recent version of the parent protocol for details not 
described within this addendum.  The purpose of this addendum is to provide details and requirements 
unique to participation in the FX addendum portion of the study.  
4.2. Purpose 
The purpose of this addendum is to collect post-market clinical evidence on valve performance and 
procedural outcomes associated with the Evolut FX Device. 

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5. Objective and Endpoints 
5.1. Objective 
The purpose of this addendum is to collect post-market clinical evidence in the United States, on valve 
performance and procedural outcomes associated with the Evolut FX Device. 
5.2. Endpoints 
The following endpoints will be used to evaluate valve performance and procedural outcomes 
associated with the Evolut™ FX System. 
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  
• Percentage of subjects with an NCC depth of implant between 1.0 and 5.0 mm 
• Percentage of subjects with an absolute canting value |NCC-LCC| of ≤ 2.0 mm 
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 
• 
Percent of patients with a major vascular complication 
• 
Percent of patients that require a recapture or resheath of the TAV 
• 
Percent of patients in which the target depth of implant was achieved 
• 
Orientation of valve relative to native anatomy 
5.2.4. 
Rationale 
The basis for the selection of these study endpoints include: 
• 
Clinically relevant outcomes of the Evolut™ FX System 

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• Objectively defined and measurable in the majority of subjects 
• Consistent with current recommendations for endpoints in TAVR clinical studies(1)  
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; echocardiographic trial endpoint results will be 
based on Core Lab assessments. 
• 
Subjects will be screened to confirm eligibility for enrollment with pre-defined inclusion and 
exclusion criteria. 
6.1. Duration 
The enrollment period is estimated to be approximately 12 months and subjects will be followed for one 
year post index procedure; therefore, the estimated total duration of the addendum (first subject 
enrolled to last subject completing his/her last follow-up exam) is estimated to be approximately 24 
months.  
6.2. Study Oversight 
Refer to the Optimize PRO Parent Protocol for details of study oversight. 
6.3. Trial Organization 
Refer to the Optimize PRO parent protocol for details on participating site requirements, site principal 
investigators (PIs), site heart teams, the publications committee, and trial training. 
 
7 Product Description 
7.1 Description of Devices  
 

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Figure 1. Evolut FX System – changes from Evolut PRO+ include radiopaque gold markers for enhanced 
visualization, a single spine outer shaft, longer and stiffer stability member, flexible capsule, 3 way stopcock, and 
redesigned tip. 
 
7.1.2.1 Medtronic Evolut FX Transcatheter Aortic Valve 
The Medtronic Evolut FX TAV is available in 4 sizes (23, 26, 29, & 34mm), covering an aortic annulus 
diameter of 18 to 30 mm.  For the 26mm and 29mm bioprostheses: If the patient’s annulus diameter is 
within 0.5 mm of the upper or lower bound of the range, use of the larger valve size can be considered, 
provided additional dimensional criteria as outlined in the Clinical Investigation Plan (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, as well 
as 3 gold radiopaque markers located approximately 3 mm from the inflow of the frame.  These 
radiopaque markers are aligned below the 3 tissue commissure pads, between the inner tissue skirt and 
the outer tissue wrap, and serve to enhance visualization during implant.  The TAV is processed with an 
anti-mineralization treatment of AOA, a compound derived from oleic acid, a naturally occurring long-
chain fatty acid.  With the exception of the markers added to the frame, there are no changes to the 
frame compared to the Evolut PRO+ TAV. 

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7.1.2.2 Medtronic Evolut FX Delivery System 
The Evolut FX DCS is available in two sizes: 18 Fr and 22 Fr.  The 18 Fr FX DCS (hereafter 23-29 mm 
Evolut FX DCS) is compatible with the Evolut FX 23-29 mm TAVs and the 22 Fr FX DCS is compatible with 
the Evolut FX 34 mm TAV. The delivery catheter systems are designed to be compatible with commercial 
0.035” intravascular wires, and 18 Fr and 22 Fr introducers. The DCS Fr size / TAV compatibility and the 
compatibility with commercial intravascular wires and introducers is identical to Evolut PRO+.  Changes 
have been made to the tip, capsule, stability member, outer shaft, ILS stopcock and to the handle in 
order to improve overall ease of use through reduced insertion forces tracking forces of the DCS in 
tortuous anatomies while preserving stability during deployment. 
The DCS consists of a catheter with an integrated handle to assist the user with accurate and controlled 
deployment.  The handle features a gray front grip used to stabilize the system.  The deployment knob 
turns to deploy the bioprosthesis.  Arrows on the deployment knob indicate the direction of rotation 
required to deploy the bioprosthesis.  If desired, the deployment knob can be turned in the opposite 
direction to partially or fully recapture the bioprosthesis if the radiopaque capsule marker band has not 
yet reached the distal end of the radiopaque paddle attachment.  Once the radiopaque capsule marker 
band reaches the distal end of the radiopaque paddle attachment, it is at the point of no recapture.  The 
deployment knob also features a trigger, which can be engaged to make macro adjustments to the 
capsule position.  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. 
7.1.2.3 Evolut FX Loading System 
The Evolut FX compresses the bioprosthesis into the catheter.  There have been no changes made 
between the Evolut PRO+ and FX loading systems.  This loading system is designed for compatibility 
with this specific TAV and delivery system. 
7.2 Manufacturer 
The legal manufacturer and design site of the Evolut FX system is as follows: 
Medtronic CoreValve LLC 
 
  
7.3 Intended Population 
The study population includes patients with symptomatic native aortic valve stenosis necessitating valve 
replacement.  Patients who undergo an emergency procedure should not be included in this study.   

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7.4 Product Training Requirements 
The Evolut FX system will be used within the commercially approved indication in the United States, 
with exception to any inclusion and exclusion criteria in this protocol, and obtained by the study sites 
according to standard hospital procedures for commercial products.  Local existing approved procedures 
for commercial product regarding training, distribution, shipment, storage, and handling will be 
followed. In the event of a device malfunction or explant, refer to the Optimize PRO parent protocol. 
7.5 Product Labeling, Tracking, and Accountability  
Refer to the Optimize PRO parent protocol for product tracking, labeling, and accountability. 
7.6 Product Storage 
Sites will follow their institutional standard practice for storing commercial TAVR product. 
 
8 Study Site Requirements 
8.1 FX Addendum Site Activation 
All sites should be activated to the parent protocol prior to, or concurrent with, FX Addendum 
activation.  Full Ethics Committee (EC) or Institutional Review Board (IRB) approval/acknowledgement 
should be received prior to beginning study activities. 
Prior to activation to the addendum, Medtronic will train study site personnel on this clinical 
investigation plan addendum, and any corresponding changes to the informed consent or data 
collection and reporting tools. If new members join the study site team, they will receive training on the 
applicable study requirements relevant to their role before contributing to the study. 
Medtronic will provide each study site with documentation of study site/investigator readiness; this 
letter must be received prior to performing study addendum related activities. 
 

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9 Selection of Subjects 
9.1 Study Population 
The study population includes patients with symptomatic native aortic valve stenosis that necessitates 
valve replacement who meet the criteria for on-label use of the Evolut™ FX system in accordance with 
the Instructions for Use and local regulations. 
9.2 Subject Enrollment 
This addendum will involve approximately 150 subjects in the US, 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 40 subjects without prior 
authorization from Medtronic.  Subjects who exit from the study after implantation will not be replaced.    
9.3 Inclusion Criteria 
Prospective subjects must meet all of the following inclusion criteria to be eligible for participation: 
1. Acceptable candidate for treatment with the Evolut™ FX system in accordance with the 
commercial Instructions for Use and local regulations 
2. Subject is symptomatic from his/her aortic valve stenosis, as demonstrated by New York Heart 
Association (NYHA) Functional Class II or greater 
3. Subject and the treating physician agree that the subject will return for all required post 
procedure follow-up visits 
4. Anatomically suitable for transfemoral TAVR with the Medtronic TAVR system 
5. Subject meets the legal minimum age to provide Informed Consent based on local regulatory 
requirements 
9.4 Exclusion Criteria 
Subjects are not eligible for study participation if they meet ANY of the following exclusion criteria: 
1. Contraindicated for treatment with the Evolut™ FX system in accordance with the commercial 
Instructions for Use  
2. Anatomically not suitable for the Evolut™ FX system 
3. Previous aortic valve replacement 
4. Reduced ventricular function with left ventricular ejection fraction (LVEF) < 35% as measured by 
resting echocardiogram 
5. Frailty assessments identify: 

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

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10 Study Procedures 
10.1 Schedule of Events 
Protocol required follow-up evaluations should be performed at the trial site.  Remote visits via phone 
contact are permitted, if necessary.  The protocol required evaluations for each trial interval are listed as 
follows and summarized in Table 2. 
10.1.1 
Screening and Enrollment Procedures  
Refer to the Optimize PRO parent protocol for screening and enrollment procedures.  Training specific to 
implanting the Evolut FX TAV will be required prior to enrolling in the addendum. 
 
10.1.2 
Implant Procedure (TAVR) and peri-procedural data collection 
Refer to the Optimize PRO parent protocol for details pertaining to the implant procedure, pre- and peri-
procedural data collection, including 12-lead ECG timepoints, required laboratory tests, and procedural 
angiograms confirming cusp overlap view.  In addition to the views specified in the Optimize PRO parent 
protocol, fluoroscopy images in the LAO view are required to be saved at the following two time points: 
• 
Prior to crossing the aortic arch 
• 
In the ascending aorta prior to switching to RAO view, ideally immediately prior to crossing the 
annulus 
If the aortic arch is recrossed for the purpose of aligning the commissures, a second set of the two 
images listed above will be required. 
A post-procedure MSCT with contrast has been added for the purpose of assessing coronary-
commissure overlap, and can be collected anytime post-procedure through the 30 day follow-up visit. 
Procedural aspects specific to the Medtronic TAVR system should be performed according to the 
Instructions for Use.   
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 in the Optimize PRO parent protocol. 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. 

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10.1.2.1 
External ECG Monitors 
The conduction disturbance pathway indicates in some circumstances that the subject should be 
discharged home with an external ECG monitor (Holter monitor).  Holter monitors will be provided to 
participating sites for the FX addendum.  
10.1.3 
Follow-Up Evaluations 
Refer to the Optimize PRO parent protocol for requirements for 30-day and 12-month follow-up visits.  
Note a Modified Rankin Score assessment should be conducted at 1 and 3 months following any stroke 
event. 
 
10.1.3.1 
Visit Windows 
Day 0 = day of index procedure 
• 
30 Day (30 + 14 days) 
• 
12 months (365 ± 30 days) 
 
 

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10.1.5 
Missed Follow-Up Visits 
Refer to the Optimize PRO parent protocol for instructions on the handling of missed follow-up visits. 
10.1.6 
Core Labs  
Refer to the Optimize PRO parent protocol for details on Core Labs utilized for this study.  The ECG Core 
Lab will not be utilized for the FX Addendum. 
10.1.7 
Subject Consent 
A separate subject consent form will be provided for this addendum.  Refer to the Optimize PRO parent 
protocol for instructions pertaining to obtaining subject consent and revisions to informed consent 
forms. 
10.2 Assessment of Efficacy 
Refer to the Optimize PRO parent protocol for assessments of efficacy. 
10.3 Assessment of Safety 
Refer to the Optimize PRO parent protocol for assessments of safety including adverse events and 
device deficiencies. 
10.4 Device Malfunction or Explant 
Refer to the Optimize PRO parent protocol for instructions pertaining to device malfunction or explant. 
10.5 Data Collection 
Refer to the Optimize PRO parent protocol for details pertaining to data collection. 
10.5.1 Source Documents 
Refer to the Optimize PRO parent protocol for source documentation requirements. 
10.6 Deviation Handling 
Refer to the Optimize PRO parent protocol for details on deviation handling. 

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10.7 Subject Exit, Withdrawal or Discontinuation  
Refer to the Optimize PRO parent protocol for details on subject exit, withdrawal or discontinuation. 
11 Risks and Benefits 
11.1 Potential Risks 
There are possible risks and side effects connected to the Evolut™ FX TAV implant, but the risks are 
the same as those for an implant of the Evolut FX™ TAV without participation in this study, with the 
exception of the incremental risks associated with the post-procedure CT scan.  Standard risks 
associated with use of the Evolut™ FX system in the study are provided in the Instructions for Use. 
Risks and events will be continuously monitored, assessed, and documented by the investigator. 
11.2 Potential Benefits 
Participation in this clinical study will not result in any direct benefit to the patient. Trial subjects 
implanted with an Evolut™ FX device receive the same medical treatment as if they were not 
participating in this post-market study. Participation contributes to expansion of the knowledge base 
with respect to the use of the Evolut™ FX system in a routine hospital setting. 
11.3 Risk-Benefit Rationale 
Refer to the Optimize PRO parent protocol for discussion on risk minimization, alternative therapies, and 
results from the risk analysis and justification for this study. 
12 Adverse Events and Device Deficiencies  
Refer to the Optimize PRO parent protocol for requirements pertaining to Adverse Events and Device 
Deficiencies.  
12.1 Emergency Contact Details for Reporting AEs and Device 
Deficiencies 
Investigators should contact their Medtronic clinical trial monitor or site manager if they have any 
questions regarding reportable AEs.  Medtronic will provide and maintain a listing of current contact 
details for each site. 
 

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13 Statistical Design and Methods 
13.1 
General Aspects of Analysis 
13.1.1 Enrolled Population 
Within the enrolled population the following analysis sets are distinguished: 
• 
The attempted implant set: The attempted implant set consists of all enrolled subjects with an 
attempted TAVR implant procedure, defined as when the subject is brought into the procedure 
room and any of the following have occurred: anesthesia or conscious sedation administered, 
vascular line placed, TEE placed, or any monitoring line placed. Subjects will be analyzed according 
to their first attempted procedure. Enrolled subjects that do not receive an attempted TAVR implant 
are to be exited from the study. 
• 
The implanted set: The implanted set consists of all the attempted implant subjects who are 
actually implanted with the TAV.  Subjects with an attempted implant that do not actually receive a 
TAV are to be exited from the study following discharge from the index hospitalization. 
• 
Per protocol (PP) set 1 for TAVR care pathway: This per protocol set consists of all implanted 
subjects with percutaneous and transfemoral access only and no concomitant procedures including 
percutaneous coronary intervention (PCI). This per protocol set 1 will be used for the secondary 
endpoint median days from index procedure to discharge. Time zero begins on the date of the first 
attempted implant procedure. 
• 
Per protocol (PP) set 2 for conduction disturbance pathway: This per protocol set consists of all 
attempted implant subjects whose peri and post TAVR index procedure follows the conduction 
disturbance pathway management and cusp overlap technique. This per protocol set 2 will be used 
for the secondary endpoint rate of pacemaker implant for new onset or worsening conduction 
disturbance at 30 days. 
The primary analysis for the primary objective and secondary safety and effectiveness objectives will use 
the attempted implant set.   
13.2 
Description of Baseline Variables 
Baseline demographic and clinical variables will be summarized for the attempted implant, implanted, 
and per protocol sets.  Continuous variables will be summarized as means, medians, standard 
deviations, first and third quartiles, 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.  The primary endpoint analysis will be conducted after the last subject has had the 
opportunity to be followed through 30 days post procedure. 
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 
This study is not hypothesis driven; therefore, the sample size for the attempted implant population is 
not guided by statistical principals and is fixed at approximately 150 subjects at approximately 10 sites in 
the US. 
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 
• 
Percentage of subjects with an NCC depth of implant between 1.0 and 5.0 mm 
• 
Percentage of subjects with a canting absolute value |NCC-LCC| of ≤ 2.0 mm 
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 
• 
Percentage of subjects with a major vascular complication at 30 days 
• 
Percentage of subjects that require a recapture or resheath of the TAV 
• 
Percentage of subjects in which the target depth of implant was achieved 
• 
Orientation of valve relative to native anatomy 

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13.7 
Missing Data 
Refer to the Optimize PRO parent protocol for details pertaining to missing data. 
14 Ethics 
14.1 Statement of Compliance 
Refer to the Optimize PRO parent protocol for a statement of compliance. 
15 Study Administration 
15.1. Monitoring  
Refer to the Optimize PRO parent protocol for details pertaining to monitoring. 
15.2. Data Management 
Refer to the Optimize PRO parent protocol for details pertaining to data management. 
15.3. Direct Access to Source Data/Documents  
Refer to the Optimize PRO parent protocol for details pertaining to direct access to source data and 
documents. 
15.4. Confidentiality 
Refer to the Optimize PRO parent protocol for confidentiality information. 
15.5. Liability 
Refer to the Optimize PRO parent protocol for liability information. 
15.6. CIP Amendments 
Refer to the Optimize PRO parent protocol for information on CIP Amendments. 
15.7. Record Retention 
Refer to the Optimize PRO parent protocol for details pertaining to record retention. 

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15.8. Publication and Use of Information 
Refer to the Optimize PRO parent protocol for details pertaining to publication and the use of study 
information. 
15.9. Suspension or Early Termination 
Refer to the Optimize PRO parent protocol for details pertaining to suspension or early termination of 
the study or individual study sites. 
16 Other Institutions and Professional Services 
Refer to the Optimize PRO parent protocol for details pertaining to Core Labs and any other professional 
services provided for this study. 
17 References 
 
1. Gilard M et al. Registry of Transcatheter Aortic-Valve Implantation in High-Risk Patients. New 
England Journal of Medicine 2012:1705-1715. 
2. International Standard ISO 14155:2011(E).  Clinical investigation of medical devices for human 
subjects - Good Clinical Practice 
 
18 Appendices 
The Post-Procedure CT Requirements are listed below.  Refer to the Optimize PRO parent protocol for all 
other Appendices. 
 
 
18.1 Appendix I: Post-Procedure MSCT Requirements 
18.1.1 
General Requirements 
• 
Multi-detector CT scanner (64-slice minimum) with ECG-gating capability. 
• 
ECG-gated contrast enhanced aortic root (slice thickness of ≤1.0 mm). 
• 
Temporal resolution should be optimized to reduce motion artifact. 

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• 
Specified additional fluoroscopy images required prior to 
crossing aortic arch and immediately before crossing the 
annulus 
• 
Clarified Discharge CT will need to be with contrast 
• 
Updated that External ECG (Holter) monitors will be 
provided to the sites for the FX addendum 
• 
Stated ECG Core Lab will not be utilized for FX 
• 
Changed primary endpoint timing to after the last subject 
is followed for 30 days post-procedure 
• 
Added appendix with Discharge CT requirements 
3.0 
• 
Expanded window for post-procedure CT to be anytime 
between TAVR implant and 30 day follow-up visit 
• 
Corrected reference 2 to cite International Standard ISO 
14155:2011(E) 
• 
Added footnote to Table 2 clarifying that discharge TTE 
should be done between 12 hours and 7 days post TAVR 
• 
Corrected interquartile range to first and third quartiles in 
description of baseline variables 
• 
Clarified the Primary Endpoint to occur after the last 
subject has had the opportunity to be followed through 30 
days 
• 
Clarified that this study is not hypothesis driven, and that 
sample size is not determined by statistical principles.