Safety and Effectiveness of Edwards Lifesciences SAPIEN XT Transcatheter Heart Valve in the Chinese Population
Phase: NA
Conditions: Aortic Stenosis, Symptomatic Aortic Stenosis, Aortic Regurgitation
Sponsor: Edwards Lifesciences

PROPRIETARY DATA: This document and the information contained herein may not be reproduced, used or 
disclosed without written permission from Edwards Lifesciences LLC 
Edwards Lifesciences, Edwards, the stylized logo, and SAPIEN XTTM are trademarks of Edwards Lifesciences Corporation 
 
 
 
 
Safety and Effectiveness of Edwards Lifesciences SAPIEN XTTM Transcatheter 
Heart Valve (THV) in the Chinese Population 
 
 
 
 
 
NCT03314857 
 
 
 
 
 
 
February 7, 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table of Contents 
1. 
Study Synopsis ......................................................................................................................... 5 
2. 
Introduction ............................................................................................................................. 9 
2.1 
Study Purpose .................................................................................................................. 9 
2.2 
Clinical Background .......................................................................................................... 9 
2.2.1 
Disease Process ....................................................................................................... 10 
2.2.2 
Alternative Therapies/Techniques .......................................................................... 10 
3. 
Study Device .......................................................................................................................... 12 
3.1 
SAPIEN XT Transcatheter Heart Valve ............................................................................ 12 
3.1.1 
NovaFlex+ Delivery System ..................................................................................... 13 
3.1.2 
Expandable Introducer Sheath Set ......................................................................... 14 
3.1.3 
Edwards Transfemoral Balloon Catheter ................................................................ 14 
3.1.4 
RetroFlex Dilator Kit ................................................................................................ 14 
3.1.5 
Crimper ................................................................................................................... 14 
3.1.6 
Qualcrimp ................................................................................................................ 14 
3.1.7 
Inflation Devices ...................................................................................................... 14 
3.2 
Instructions for Use (IFU) ............................................................................................... 15 
4. 
Study Objective ...................................................................................................................... 15 
4.1 
Primary Endpoint............................................................................................................ 15 
4.2 
Secondary Endpoints ...................................................................................................... 15 
5. 
Patient Population ................................................................................................................. 16 
5.1 
Inclusion Criteria ............................................................................................................ 16 
5.2 
Exclusion Criteria ............................................................................................................ 16 
6. 
Investigation Plan .................................................................................................................. 17 
6.1 
Study Design ................................................................................................................... 17 
6.2 
Study Compliance and Regulations ................................................................................ 18 
6.3 
Study Procedures ........................................................................................................... 19 
6.3.1 
Informed Consent ................................................................................................... 20 
6.3.2 
Patient Screening and Enrolment ........................................................................... 20 
6.3.3 
Study Procedures .................................................................................................... 21 
6.3.4 
Missed Visits ........................................................................................................... 30 
6.3.5 
Study Termination .................................................................................................. 30 
6.3.6 
Standard of Care ..................................................................................................... 31 
7. 
Study Material & Methods .................................................................................................... 31 
7.1 
Study Device ................................................................................................................... 31 

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7.2 
Storage & Labeling ......................................................................................................... 31 
7.3 
Device Accountability ..................................................................................................... 31 
8. 
Evaluation of Safety ............................................................................................................... 32 
8.1 
Adverse Event Assessments ........................................................................................... 32 
8.1.1 
Investigator Assessment Responsibilities ............................................................... 32 
8.1.2 
Sponsor Assessment Responsibilities ..................................................................... 32 
8.1.3 
Medical Reviewer Responsibilities ......................................................................... 32 
8.2 
Device Deficiency ........................................................................................................... 32 
8.3 
Adverse Event Reporting ................................................................................................ 33 
8.4 
SAE and USADE Reporting .............................................................................................. 33 
8.5 
Device Deficiency and Vigilance Reporting .................................................................... 34 
8.6 
Source Documents ......................................................................................................... 34 
9. 
Risk Evaluation ....................................................................................................................... 34 
9.1 
Potential Risk to Study Subjects ..................................................................................... 34 
9.2 
Methods to Minimize Risk .............................................................................................. 34 
9.3 
Study Site Criteria ........................................................................................................... 35 
9.4 
Benefits........................................................................................................................... 35 
9.5 
Risk-Benefit Analysis ...................................................................................................... 36 
10. Definitions .............................................................................................................................. 36 
11. Statistical Considerations ...................................................................................................... 43 
11.1 Sample Size ..................................................................................................................... 43 
11.2 Timing ............................................................................................................................. 43 
11.3 Analysis Sets ................................................................................................................... 43 
11.4 Missing Data ................................................................................................................... 44 
11.5 Endpoint Analysis ........................................................................................................... 44 
12. Study Administration ............................................................................................................. 44 
12.1 General Study Organization ........................................................................................... 44 
12.2 Medical Reviewers ......................................................................................................... 45 
12.3 Echocardiography Core Laboratory ............................................................................... 45 
12.4 Clinical Sites .................................................................................................................... 45 
12.5 Site Training .................................................................................................................... 45 
12.6 Study Monitoring ........................................................................................................... 46 

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12.7 Data Collection and Quality Assurance .......................................................................... 47 
12.8 Publication Policy ........................................................................................................... 48 
13. Ethical Review and Consideration ......................................................................................... 48 
13.1 Confidentiality ................................................................................................................ 48 
13.2 Records and Reports ...................................................................................................... 48 
13.2.1 
Records ................................................................................................................... 48 
13.2.2 
Deviations from Protocol ........................................................................................ 49 
13.2.3 
Record Retention Policy .......................................................................................... 49 
14. Financial and Insurance Considerations ................................................................................ 49 
14.1 Clinical Trial Funding ...................................................................................................... 49 
14.2 Clinical Trial Insurance .................................................................................................... 50 
15. References ............................................................................................................................. 50 
Appendix A: Assessments for Stroke and Stroke Severity………………………...………………….……………..A 
Appendix B: Frailty Index…………………………………………………………………….………………………………..……B 
Appendix C: 6 Minute Walk Test…………………….……………………………………………………………………….….C 
Appendix D: Clinical Trial Report Contents…………………….……………………………………………………………D 
 
 
 

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1. Study Synopsis 
Title 
Safety and Effectiveness of Edwards Lifesciences SAPIEN XTTM 
Transcatheter Heart Valve (THV) in the Chinese Population 
Study Purpose 
To evaluate the safety and effectiveness of the SAPIEN XT 
(Edwards Lifesciences, Irvine, California) transcatheter heart 
valve implantation (TAVI) in Chinese patients with 
symptomatic severe calcific aortic stenosis who are considered 
at high risk for surgical valve replacement. 
Study Design 
Prospective, single-arm, multi-center study.  The study is 
expected to take 5.5 years to complete. 
Study Device 
Edwards SAPIEN XT™ Transcatheter Heart Valve and NovaFlex+ 
delivery system  
Study Population 
A maximum of 60 patients with symptomatic severe calcific 
aortic stenosis requiring transcatheter aortic valve 
implantation (TAVI), who are considered high risk for surgical 
valve replacement who receive a SAPIEN XT THV. 
Inclusion Criteria 
1. Subjects who are considered to be operable and high risk 
for surgical valve replacement: 8 ≤ STS Score ≤ 15 or 15 ≤ 
Logistic EuroSCORE ≤ 40.  If STS score is below 8 and/or 
Logistic EuroSCORE is below 15, patients should have other 
clinical or anatomical risk factors that would be considered 
high risk for surgery and documented by the heart team 
2. Severe symptomatic aortic stenosis requiring aortic valve 
replacement characterized by one or more of the following 
within 60 days prior to the index procedure: AVA < 0.8 cm2, 
Indexed AVA <0.5 cm2/m2, mean gradient > 40mmHg, or 
peak aortic jet velocity > 4.0m/sec. [41] 
3. NYHA Functional Class II or greater.  
4. The study patient or the study patient’s legal 
representative has been informed of the nature of the 
study, agrees to its provisions and has provided written 
informed consent as approved by the EC of the respective 
clinical site.  
5. The study patient agrees to comply with all required post-
procedure follow-up visits. 
6. Native aortic valve annulus area between 314 mm2 - 660 
mm2 as measured by CT. 

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7. Native aortic annulus diameter between 20 mm – 29 mm as 
measured by CT. 
Exclusion Criteria 
1. Evidence of an acute myocardial infarction ≤ 1 month (30 
days) before the intended treatment [(defined as: Q wave 
MI, or non-Q wave MI with total CK elevation of CK-MB ≥ 
twice normal in the presence of MB elevation and/or 
troponin level elevation (WHO definition)]. 
2. Aortic valve is a congenital unicuspid or is non-calcified. 
3. Aortic valve is bicuspid and the patient is less than 60 years 
old, or the aortic valve is bicuspid with no raphe (Sievers 
classification type 0) [42] 
4. Anomalous coronary artery that would interfere with 
proper placement of the valve. 
5. Mixed aortic valve disease (aortic stenosis and aortic 
regurgitation with predominant aortic regurgitation >3+). 
6. Pre-existing mechanical or bioprosthetic valve in any 
position.  
7. Any therapeutic invasive cardiac procedure resulting in a 
permanent implant that is performed within 30 days of the 
index procedure.  Implantation of a permanent pacemaker 
or ICD is not considered exclusion criteria. 
8. Any patient with a balloon valvuloplasty (BAV) within 30 
days of the procedure (unless BAV is a bridge to procedure 
after a qualifying echocardiogram). 
9. Leukopenia (WBC < 3000 cell/mL), acute anemia (Hgb < 9 
g/dL), Thrombocytopenia (Plt < 50,000 cell/mL).  
10. Renal insufficiency (creatinine > 3.0 mg/dL) and/or renal 
replacement therapy at the time of screening. 
11. Untreated clinically significant coronary artery disease 
requiring revascularization. 
12. Emergency interventional/surgical procedures within one 
month (30 days) prior to the TAVI procedure.  
13. Hypertrophic cardiomyopathy with or without obstruction 
(HOCM). 
14. Severe ventricular dysfunction with LVEF < 20%. 
15. Echocardiographic evidence of intracardiac mass, 
thrombus or vegetation. 
16. Active upper GI bleeding within 3 months (90 days) prior to 
procedure.  
17. A known contraindication or hypersensitivity to all 
anticoagulation regimens, or inability to be anticoagulated 
for the study procedure. 

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18. Stroke or transient ischemic attack (TIA) within 3 months 
(90 days) of the procedure. 
19. Estimated life expectancy < 12 months (365 days) due to 
carcinomas, chronic liver disease, chronic renal disease or 
chronic end stage pulmonary disease. 
20. Significant aortic disease, including marked tortuosity 
(hyperacute bend), aortic arch atheroma [especially if thick 
(> 5 mm), protruding or ulcerated] or narrowing (especially 
with calcification and surface irregularities) of the 
abdominal or thoracic aorta, severe “unfolding” and 
tortuosity of the thoracic aorta. 
21. Iliofemoral vessel characteristics that would preclude safe 
placement of the introducer sheath. 
22. Currently participating in an investigational drug or 
another device study.  Note: Trials requiring extended 
follow-up for products that were investigational, but have 
since become commercially available, are not considered 
investigational trials. 
23. Active bacterial endocarditis within 6 months (180 days) of 
procedure, with our without treatment. 
Primary Endpoint 
All-cause mortality at 30 days 
Secondary Endpoints 
Safety 
• Cardiovascular mortality at 30 days 
• Stroke at 30 days 
• TIA at 30 days 
• All-cause mortality & stroke at 30 days 
• Vascular complications (major) at 30 days 
• Bleeding complications (life threatening or disabling, and 
major) at 30 days 
• Myocardial infarction at 30 days 
• Acute kidney injury at 30 days (stages II and III) 
• Coronary obstruction requiring intervention at 30 days 
• Permanent pacemaker implantation at 30 days 
 
Device Success 
• Absence of procedural mortality AND 
• Correct positioning of a single prosthetic heart valve into 
the proper anatomic location AND 
• Intended performance of the prosthetic heart valve (no 
prosthesis-patient mismatch and mean aortic valve 

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gradient <20mmHg or peak velocity <3m/s, AND no 
moderate or severe prosthetic valve regurgitation) at 30 
Days 
Efficacy 
• New York Heart Association (NYHA) Classification at 30 
days 
• Hemodynamic valve performance evaluation by 
echocardiography for aortic valve stenosis and aortic 
valve regurgitation (paravalvular & central) at 30 Days 
as determined by Echo core lab 
Patient Follow-up Schedule 
Patients consented to trial and implanted with a SAPIEN XT 
THV will be assessed at Baseline, Peri- and Post-Procedure, 
Index Hospitalisation Discharge, and 30 Days, 6 Months, 1 
Year, 2 Years, 3 Years, 4  Years and 5 Years post-procedure.  
Study Duration 
Subjects implanted with SAPIEN XT THV will be followed for 5 
years after the procedure 
Statistical Considerations 
The sample size of 50-60 patients is determined per Chinese 
regulatory requirements and agreement for a regional study of 
a medical device already approved in other regions based on a 
well-designed prospective study. 
Sponsor 
Edwards Lifesciences LLC 
One Edwards Way 
Irvine, CA 92614 USA 
Local Sponsor 
Edwards (Shanghai) Medical Products Co. Ltd 
 
 
Sponsor Representative / 
Study Manager 
 
THV Clinical Project Manager 
Edwards Lifesciences Pty Ltd 
 
 
Principal Investigator 
Prof Runlin GAO 
Fuwai Hospital 
 

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Beijing, China 
Study Centers 
Fuwai Hospital, CAMS&PUMC 
Beijing, China 
 
Prof Mai CHEN 
WestChina Hospital, Sichuan University 
Chengdu, China 
 
Prof Jianan WANG 
The Second Affiliated Hospital of Zhejiang University School of 
Medicine 
Hangzhou, China 
Contract Research 
Organization (CRO) 
 
  
 
  
 
2. Introduction 
2.1 
Study Purpose 
The purpose of this trial is to evaluate the safety and effectiveness of the SAPIEN XT 
transcatheter heart valve implantation (TAVI) in Chinese patients with symptomatic severe 
calcific aortic stenosis who are considered at high risk for surgical valve replacement. Clinical 
data will be submitted for the purposes of obtaining Chinese regulatory approval.   
2.2 
Clinical Background 
Prolonged average life expectancy has resulted in an aging population and consequently, an 
increase in the number of patients with acquired, calcific, severe, symptomatic aortic stenosis 
(AS). The standard of care therapy for patients suffering from severe AS is aortic valve 
replacement surgery (AVR). In the aged population, many patients are too sick to be operated 
or have co-morbidities that preclude the option for surgery [1]. 
 
AS is a progressive, debilitating and life-threatening disease if left untreated. Affected 
individuals are typically > 65 years of age. The pathology involves progressive calcification of the 
leaflet bodies which limits normal cusp opening during systole. Cellular aging and degeneration 
have been implicated in this form of the disease and diabetes mellitus and 
hypercholesterolemia are risk factors. 
 

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2.2.1 
Disease Process 
The pathophysiology of AS includes an increase in afterload, progressive hypertrophy of the left 
ventricle, and a decrease in systemic and coronary blood flow as consequences of valve 
obstruction. Typically, patients with AS are free from cardiovascular symptoms (e.g. angina, 
syncope and/or heart failure) until late in the course of the disease. However, once symptoms 
manifest, the prognosis is poor, especially when associated with congestive heart failure. 
Death in general, including sudden death, occurs primarily in symptomatic patients. Survival 
analyses have demonstrated that the interval from onset of symptoms to time of death is 
approximately two years in patients with heart failure, three years in those with syncope, and 
five years in those with angina [2]. Among symptomatic patients with moderate-to-severe AS 
treated medically, mortality rates after the onset of symptoms were approximately 25% at 1 
year and 50% at 2 years and more than 50% of deaths were sudden [3]. 
 
Grading the severity of AS is based on a variety of hemodynamic and natural history data. 
According to the ACC/AHA guideline authors, AS is best described as a continuum. In patients 
with moderate-to-severe AS, valve area may decline up to 0.3 cm2 per year and the systolic 
pressure gradient across the valve can increase by as much as 15-19 mmHg per year, with a 
higher rate of progression observed in elderly patients with coronary artery disease 
(CAD) and chronic renal insufficiency [4]. Relief of aortic valve obstruction typically results in an 
improvement of symptoms, hemodynamic parameters, and global left ventricle systolic 
function, as well as reversal of left ventricular hypertrophy [4,5]. 
 
2.2.2 
Alternative Therapies/Techniques 
Treatment options for patients suffering from symptomatic AS include palliation of symptoms 
without valve replacement (non-surgical standard therapy), surgical aortic valve replacement 
(AVR) or TAVI with another valve. Treatment options are determined by patient risk for 
morbidity or mortality after surgery and patient choice. Non-surgical treatment options 
including balloon aortic valvuloplasty have been demonstrated to lead to shortened life 
expectancies and poor quality of life [6-8]. Patients considered poor candidates for AVR 
typically present with significant morbidities or anatomic limitations, such as severely calcified 
aorta, chest wall radiation, etc. [9]. Also a state of frailty may lead to a patient or physician 
decision to forego surgery. AVR has been demonstrated to have excellent long term outcomes 
for patients with aortic valve stenosis, including patients who were operable but had predicted 
high risk for surgery (by STS PROM > 10) [10-15]. 
 
Transcatheter aortic valve implantation (TAVI) was first performed in man in 2002 and was 
followed by European commercialization in 2007 [16-18]. Today more than 160,000 patients 
worldwide have undergone TAVI and there is a proliferation of published literature supporting 

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the safety and performance of the SAPIEN balloon expandable heart valve (SAPIEN, SAPIEN XT, 
and SAPIEN 3). The Edwards THV clinical research program includes more than 15,000 patients 
enrolled in approximately 23 clinical studies which include first-in-man, feasibility, pivotal 
randomized controlled trials and post-market registries. Results from these trials have been 
publicly reported in the scientific congresses and journals [19-34]. 
 
The PARTNER (I) trial was the first of its kind to randomize patients to THV versus the current 
standard of care, and has produced the most conclusive evidence of the safety and 
effectiveness of the Edwards SAPIEN THV in both high risk surgical (Cohort A) and inoperable 
patients with symptomatic aortic stenosis (Cohort B). Cohort B randomized patients between 
medical therapy and transfemoral (TF) TAVI. The one-year results for survival and functional 
improvements in both New York Heart Association (NYHA) class and Quality of Life indices 
indicated that TAVI should be the new standard of treatment for patients with severe AS 
considered to be at too high a risk to undergo surgical AVR [24, 35]. Recent results support the 
sustained benefit up to five years post TAVI [19, 21, 36]. 
 
The Cohort A randomized TAVI to AVR in patients who were considered at high operative risk 
for surgery based on the STS score [37]. While peri-procedural stroke rates were higher in the 
TAVI arm (3.8% vs. 2.1% [p=0.20]), the overall composite endpoint of all-cause mortality or 
stroke at 1 year was not different between the two arms (24.2% for TAVI vs. 26.8% for AVR 
(difference -2.6%, 95% upper confidence limit 3.0%, pre-defined margin 7.5%; p = 0.001 for 
non-inferiority). Moreover, despite the initial higher 30-day stroke rate in the TAVI arm, the 
mortality at 30 days was numerically lower in the TAVI arm (3.4% vs. 6.5% for TAVI and AVR, 
respectively). This difference did not reach statistical significance, however (p=0.07). 
Major vascular complications were more frequent after TAVI (11.0% vs. 3.2%, P<0.001), 
whereas major bleeding (9.3% vs. 19.5%, P<0.001) and new-onset atrial fibrillation (8.6% vs. 
16.0%, P<0.001) were more frequent after AVR. Both NYHA Class and Quality of Life index 
improvements favoured TAVI at 30 days, but were similar after 1 year. Paravalvular aortic 
regurgitation (PAR) was more frequent after TAVI than AVR (P<0.001), and a late association 
between residual PAR and mortality has been subsequently revealed [21].  
 
Three year data demonstrate sustained benefits for aortic valve replacement in both the TAVI 
and AVR arms with the SAPIEN valve demonstrating a sustained durability similar to surgical 
bioprostheses with no differences in long term mortality (44.2 vs. 44.8%, for TAVI vs. AVR, 
respectively)[38]. 
 
Conclusions from the first randomized Edwards SAPIEN THV studies indicate that balloon 
expandable TAVI should be recognized as the standard of care for inoperable patients and is an 

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acceptable alternative to AVR in high risk patients. Also reported were significant outcomes 
related to the study device versus standard therapy control, such as stroke, major vascular 
complications and major bleeding events which had significant impact on overall mortality. 
These findings were consistent with earlier published reports. Despite the high-risk nature of 
the population studied, it is a widely held belief that design improvements in the profile and 
ease of use of the delivery system may reduce procedure-related adverse events and thus 
support expansion of the study population to include patients previously excluded due to 
anatomical limitations. Two year data from the SOURCE XT post-approval study of the SAPIEN 
XT demonstrate similar long-term performance to the SAPIEN valve [39], with more favourable 
long-term survival for patients presenting with few comorbidities at baseline. The SAPIEN 3 is 
the most recent SAPIEN THV to obtain the CE Mark (January 2014). The SAPIEN 3 has been 
designed to be placed via a fully percutaneous TF approach using the Edwards Expandable 
Sheath (“eSheath”), and its TF delivery has demonstrated the lowest rates of death, stroke, and 
major vascular complications (2.1, 1.0 and 4.2%, respectively) for any SAPIEN THV [40]. 
The robust body of consistently improving clinical evidence presented by Edwards SAPIEN 
transcatheter valve platforms attests to the Edwards history of leadership in heart valve 
bioprosthesis technology.  
3. Study Device 
3.1 
SAPIEN XT Transcatheter Heart Valve 
The Edwards SAPIEN XT Transcatheter Heart Valve (Figure 1) is indicated for use in patients 
with severe, symptomatic, calcified aortic stenosis.   
The Edwards SAPIEN XT transcatheter heart valve (THV) is comprised of a balloon-expandable, 
radiopaque, nickel cobalt chromium frame, trileaflet bovine pericardial tissue valve, and 
polyethylene terephthalate (PET) fabric skirt.  It is treated according to the Edwards ThermaFix 
process, and is packaged and terminally sterilized in glutaraldehyde.  
 
Figure 1 
SAPIEN XT Transcatheter Heart Valve (THV) 
 

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Edwards SAPIEN XT 
Transcatheter Heart 
Valve 
9300TFX 
(23mm) 
9300TFX 
(26mm) 
9300TFX 
(29mm) 
NovaFlex+ Delivery 
System1 
9355FS23 
9355FS26 
9355FS29 
Edwards Expandable 
Introducer Sheath 
Set (“eSheath”) 
916ES23 
918ES26 
920ES29 
RetroFlex Dilator Kit 
9100DKS 
Edwards 
Transfemoral 
Balloon Catheter 
9350BC20 
9350BC23 
9350BC25 
Crimper 
9350CR 
Inflation Devices (x2) 
1Includes the Qualcrimp Crimping Accessory, and 2-piece Crimp Stopper 
 
3.1.2 Expandable Introducer Sheath Set 
The Edwards eSheath Introducer Set is intended for introduction of interventional devices in 
the vascular system.  The product is intended for use by physicians trained and experienced in 
interventional techniques.  Standard techniques for placement of vascular access sheaths 
should be employed.   
3.1.3 Edwards Transfemoral Balloon Catheter 
The balloon catheter is indicated for dilation of stenotic native aortic valve leaflets. 
 
3.1.4 RetroFlex Dilator Kit 
The RetroFlex dilator kit contains a set of four hydrophilically coated tapered dilators used for 
arterial dilatation. 
3.1.5 Crimper 
The crimper reduces the diameter of the THV to mount it to the delivery system. The crimper is 
comprised of a compression mechanism that is closed with a handle located on the housing. 
The crimper includes a 2-piece Crimp Stopper (packaged with the delivery system) used to 
correctly crimp the THV. 
3.1.6 Qualcrimp 
The Qualcrimp crimping accessory (packaged with the NovaFlex+ delivery system) is used 
during crimping of the THV. 
3.1.7 Inflation Devices 
Inflation devices with a locking mechanism are used during native valve predilation and THV 
deployment. 

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3.2 
Instructions for Use (IFU) 
These devices must always be used according to the current IFU provided with each product 
4. Study Objective 
The objective of the study is to evaluate the safety and effectiveness of the SAPIEN XT 
transcatheter heart valve implantation in Chinese patients with symptomatic severe calcific 
aortic stenosis who are considered at high risk for surgical valve replacement. 
4.1 
Primary Endpoint 
The primary endpoint is all-cause mortality at 30 days post-index procedure.   
4.2 
Secondary Endpoints 
Safety 
• Cardiovascular mortality at 30 days 
• Stroke at 30 days 
• TIA at 30 days 
• All-cause mortality & stroke at 30 days 
• Vascular complications (major) at 30 days 
• Bleeding complications (life threatening or disabling, and major) at 30 days 
• Myocardial infarction at 30 days 
• Acute kidney injury at 30 days (stages II and III) 
• Coronary obstruction requiring intervention at 30 days 
• Permanent pacemaker implantation at 30 days 
 
Device Success 
• Absence of procedural mortality AND 
• Correct positioning of a single prosthetic heart valve into the proper anatomic location 
AND 
• Intended performance of the prosthetic heart valve (no prosthesis-patient mismatch and 
mean aortic valve gradient <20mmHg or peak velocity <3m/s, AND no moderate or severe 
prosthetic valve regurgitation) at 30 Days 
Efficacy 
• New York Heart Association (NYHA) Classification at 30 days 
• Hemodynamic valve performance evaluation by echocardiography for aortic valve stenosis 
and aortic valve regurgitation (paravalvular & central) at 30 Days as determined by Echo 
core lab 

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5. Patient Population 
To ensure that a minimum of 50 patients are implanted with the SAPIEN XT THV and complete 
the 30 Day follow-up for Primary Endpoint, up to 60 patients will be enrolled and implanted 
with SAPIEN XT THV. Each site may not contribute more than 30 implanted patients to the 
study population.   All patients will be followed for 5 years. 
Enrolment will be closely monitored to ensure not more than 60 patients are implanted with 
SAPIEN XT THV. 
5.1 
Inclusion Criteria 
Patients must meet all of the Inclusion Criteria in order to participate in the study 
1. Subjects who are considered to be operable and high risk for surgical valve replacement: 
8 ≤ STS Score ≤ 15 or 15 ≤ Logistic EuroSCORE ≤ 40.  If STS score is below 8 and/or 
Logistic EuroSCORE is below 15, patients should have other clinical or anatomical risk 
factors that would be considered high risk for surgery and documented by the heart 
team 
2. Severe symptomatic aortic stenosis requiring aortic valve replacement characterized by one 
or more of the following within 60 days prior to the index procedure: AVA < 0.8 cm2, 
Indexed AVA <0.5 cm2/m2, mean gradient > 40mmHg, or peak aortic jet velocity > 
4.0m/sec. [41] 
3. NYHA Functional Class II or greater.  
4. The study patient or the study patient’s legal representative has been informed of the 
nature of the study, agrees to its provisions and has provided written informed consent 
as approved by the EC of the respective clinical site.  
5. The study patient agrees to comply with all required post-procedure follow-up visits. 
6. Native aortic valve annulus area between 314 mm2 - 660 mm2 as measured by CT. 
7. Native aortic annulus diameter between 20 mm – 29 mm as measured by CT. 
 
5.2 
Exclusion Criteria 
Patients must not meet any of the Exclusion Criteria in order participate in the study 
1. 
Evidence of an acute myocardial infarction ≤ 1 month (30 days) before the intended 
treatment [(defined as: Q wave MI, or non-Q wave MI with total CK elevation of CK-MB 
≥ twice normal in the presence of MB elevation and/or troponin level elevation (WHO 
definition)]. 
2. 
Aortic valve is a congenital unicuspid or is non-calcified. 
3. 
Aortic valve is bicuspid and the patient is less than 60 years old, or the aortic valve is 
bicuspid with no raphe (Sievers classification type 0) [42] 
4. 
Anomalous coronary artery that would interfere with proper placement of the valve. 
5. 
Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant 
aortic regurgitation >3+). 

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6. 
Pre-existing mechanical or bioprosthetic valve in any position.  
7. 
Any therapeutic invasive cardiac procedure resulting in a permanent implant that is 
performed within 30 days of the index procedure.  Implantation of a permanent 
pacemaker or ICD is not considered exclusion criteria. 
8. 
Any patient with a balloon valvuloplasty (BAV) within 30 days of the procedure (unless 
BAV is a bridge to procedure after a qualifying echocardiogram). 
9. 
Leukopenia (WBC < 3000 cell/mL), acute anemia (Hgb < 9 g/dL), Thrombocytopenia (Plt 
< 50,000 cell/mL).  
10. Renal insufficiency (creatinine > 3.0 mg/dL) and/or renal replacement therapy at the 
time of screening. 
11. Untreated clinically significant coronary artery disease requiring revascularization. 
12. Emergency interventional/surgical procedures within one month (30 days) prior to the 
TAVI procedure.  
13. Hypertrophic cardiomyopathy with or without obstruction (HOCM). 
14. Severe ventricular dysfunction with LVEF < 20%. 
15. Echocardiographic evidence of intracardiac mass, thrombus or vegetation. 
16. Active upper GI bleeding within 3 months (90 days) prior to procedure.  
17. A known contraindication or hypersensitivity to all anticoagulation regimens, or inability 
to be anticoagulated for the study procedure. 
18. Stroke or transient ischemic attack (TIA) within 3 months (90 days) of the procedure. 
19. Estimated life expectancy < 12 months (365 days) due to carcinomas, chronic liver 
disease, chronic renal disease or chronic end stage pulmonary disease. 
20. Significant aortic disease, including marked tortuosity (hyperacute bend), aortic arch 
atheroma [especially if thick (> 5 mm), protruding or ulcerated] or narrowing (especially 
with calcification and surface irregularities) of the abdominal or thoracic aorta, severe 
“unfolding” and tortuosity of the thoracic aorta. 
21. Iliofemoral vessel characteristics that would preclude safe placement of the introducer 
sheath. 
22. Currently participating in an investigational drug or another device study.  Note: Trials 
requiring extended follow-up for products that were investigational, but have since 
become commercially available, are not considered investigational trials. 
23. Active bacterial endocarditis within 6 months (180 days) of procedure, with our without 
treatment. 
 
6. Investigation Plan 
6.1 
Study Design 
This is a prospective, single-arm, multi-center study to assess the safety and effectiveness of the 
SAPIEN XT THV.  Up to 60 patients will be enrolled and implanted with the device at three sites 
in China over an estimated six month enrolment period with a follow-up period to 5 years.   
An Echocardiography Core Lab will be established for standardizing echocardiographic 
secondary endpoints.  A Medical Reviewer will review all endpoint-related adverse events. 

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6.2 
Study Compliance and Regulations 
The SAPIEN XT THV System is not commercially available in China.  The clinical investigation 
shall be conducted in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki (as updated in Fortaleza Brazil in 2013) and in compliance with China’s 
Good Clinical Practice (GCP) for Medical Devices and any national regulations. The clinical 
investigation plan and Patient Informed Consent form used to study the SAPIEN XT THV System 
must be reviewed and approved by the appropriate national authority and local or regional 
Ethics Committee (EC) where the clinical investigation is to be conducted before enrolment of 
patients may begin.  Any additional requirements imposed by the EC or regulatory authority 
shall be followed.   
Changes to the investigational plan that may increase the risk or present new risks to the 
patient must be approved in writing by Edwards Lifesciences and the EC before the change is 
implemented. 
 
 

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6.3.1 
Informed Consent 
The Patient Informed Consent Form must be approved by Edwards Lifesciences and the site’s 
EC. 
The study investigator(s) and support staff will approach patients with symptomatic aortic 
stenosis to assess their interest in participating in the study.  They will provide an overview of 
the study and device, including the background, benefits, risks, and study procedures.  If 
patients are interested in participating in the study, then they will be provided with the full 
Patient Informed Consent Form document.  Patients will be allowed to read the document in its 
entirety, and then delegated study personnel will answer all of their questions. If the patient is 
comfortable with proceeding, then they will be asked to sign and date the Patient Informed 
Consent Form.  Informed consent must be obtained prior to the screening procedures or 
baseline tests that are specific to this study.  
During the course of the study, if new information becomes available that can affect a patient’s 
future health and medical care, then the information will be provided to the patient and the 
process documented.  If relevant, all affected patients will be asked to confirm their continuing 
informed consent in writing. 
All patients who sign a Patient Informed Consent Form should be entered in the database.  Data 
should not be entered until a Patient Informed Consent Form is signed.  Patients that are 
screened and do sign a Patient Informed Consent Form should be documented on the 
Screening Log. 
6.3.2 
Patient Screening and Enrolment 
The study site shall have a committed Heart Team involved in the screening process. The 
Heart Team will include at least two cardiac surgeon, one interventional cardiologist, one 
radiologist, and one anesthesiologist but could also include (without being limited to) the 
following specialties: 
• Echocardiography 
• Gerontology 
The screening of patients in cardiovascular and cardiac surgery departments will be conducted 
by one or more delegated study team members. The study team will be responsible for 
ensuring and reporting study patient screening for study eligibility. Cumulative screening and 
enrollment logs will be maintained by study sites. Reasons for screen failures will be 
documented in study logs. 
To accommodate the implant procedure learning curve, a roll-in strategy will be available.  Each 
study site will be allowed up to two roll-in patients.  Edwards Lifesciences will document if the 

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6.3.3.1 
Screening 
The following screening data will be collected for all study patients to assess eligibility as per 
standard of care: 
• Operability Risk Assessment 
• Medical history, pertinent physical examination [include blood pressure, height, weight 
and all major systems findings] 
• NYHA functional classification 
• CSS Angina classification 
• Risk assessment (STS Risk Score, Logistic EuroSCORE, and EuroSCORE II) 
Non-Invasive Studies (must be completed within 60 days before procedure date) 
• Comprehensive transthoracic echocardiogram (TTE) (transesophageal echocardiogram 
(TEE) may be used as an alternative) 
Invasive Studies (must be completed before the procedure date) 
• Cardiac and abdominal CT angiogram with visualization of the aortic arch, both iliac and 
femoral arteries to the aorta.  In the situation where patients have compromised renal 
function that precludes the use of contrast agents, MR imaging may be used as an 
alternative to CT (≤180 days before procedure) 
• Left heart catheterization to assess the severity of aortic stenosis and severity of 
coronary artery disease (≤180 days before procedure) 
If any assessments need to be completed or repeated outside of standard of care, a patient will 
need to sign a Patient Informed Consent prior to completing assessments. 
6.3.3.2 
Baseline 
Assessments and laboratory tests are required to be completed within 30 days prior to the 
procedure date.  Assessments and laboratory tests completed outside of the 30 days will need 
to be repeated.  If completed outside of standard of care, then a Patient Informed Consent 
Form will need to be signed first. 
The following Baseline data will be collected for all study patients prior to procedure: 
• Current cardiac medications and all medications given for cardiovascular effect; 
• Neurological assessment (Appendix A) 
o NIHSS 
o MRS  
• Frailty Assessment (Appendix B) 

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• Six Minute Walk Test (Appendix C) 
• Clinical Laboratory Tests 
o Blood count (hemoglobin, hematocrit, platelet count, white blood cells) 
o PTT or PT/INR 
o CK/CK-MB and/or Troponins 
o Creatinine 
o Liver Panel (ALT, AST) 
o Albumin 
• Non-invasive studies 
o 12-Lead ECG 
o Chest x-ray 
• Adverse Event Assessment 
6.3.3.3 
Procedure 
Transfemoral access technique will be used by the investigator in his/her normal practice of 
interventional cardiology and patient selection process. 
6.3.3.3.1 
Recommended Antiplatelet/Anticoagulation Regimen  
Table 5 outlines the recommended antiplatelet regimen.  The categories were developed by 
The PARTNER II Trial Patient and Procedure Management Steering Committee. There are no 
current validated guidelines in this specific study population, however, the literature was 
surveyed and used as guidance for the following proposed guidelines. It is expected that 
specific agents and dosing regimens may vary from site to site. Patients will be assessed by the 
heart team for Category of Stroke Risk prior to prescribing treatment regimen. The Category 
and specific treatment regimen will be documented in the discharge case report form. 
Committee Categories are based on CHADS 2 score for stroke risk [40]. 
 
NOTE: The CHADS 2 score only applies to patients in atrial fibrillation (AF) and has not been 
validated in non-AF patient populations; therefore the CHADS 2 score reference was used as 
one among many guidelines to establish the risk stratification for intensity of anticoagulation 
regimen. 
Table 4 
Summary of Recommended Antiplatelet/Anticoagulation Therapy 
 
Pre procedure 
Aspirin 75-100 mg once daily 
• Patients with bare metal stent (BMS) within one month or drug 
eluting stent (DES) within 12 months should be continued on 
Clopidogrel/Prasugrel prior to their procedure 
• Patients in atrial fibrillation on warfarin should be bridged with 

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LMW or UF heparin prior to the procedure 
• Patients with persistent or paroxysmal atrial fibrillation, not on 
anticoagulation, will not be required to have a TEE to rule out 
LA thrombus prior to procedure.  If intra-procedural TEE during 
TAVI reveals thrombus, procedure will be aborted and delayed 
until patient has been on warfarin or dabigatran for 30 days.   
• In patients under concomitant TAVI/PCI, Clopidogrel loading 
with either 300mg or 600mg prior to the procedure is 
recommended in addition to ASA:  
Intra procedure 
Heparin will be given to  achieve/ maintain ACT>250 sec. 
Post procedure 
 
Category I  for Stroke Risk 
No atrial fibrillation, 
No recent stents 
• ASA 75mg once daily 
• Clopidogrel 300mg load within 6 hours of procedure (either pre 
or post) 
• Clopidogrel 75mg once daily  for at least one month post 
procedure 
 
Category II for Stroke 
Risk 
No atrial fibrillation, 
recent stents 
 
 
• ASA 75mg once daily 
• Clopidogrel 75mg once daily should be continued prior to the 
procedure and after the procedure without interruption for at 
least one month after BMS and 12 months after DES 
Category III for Stroke 
Risk 
Atrial fibrillation, no 
recent stents 
 
• ASA 75mg once daily 
• Patients should be started on warfarin or dabigatran 24 hours 
post TAVI if clinically safe and this should be continued for at 
least one month or indefinitely if possible.  If clinically safe, 
patients started on warfarin should be bridged with 
unfractionated or low molecular weight heparin until INR 
therapeutic. 
• If patients are not a candidate for warfarin or dabigatran, 
Clopidogrel 75mg once daily can be considered as an 
alternative 
 
Category IV for Stroke 
Risk  
Atrial fibrillation, 
recent stents 
• ASA 75mg once daily 
• Clopidogrel 75mg once daily for at least one month post BMS 
or 12 months post DES 
• Patients should be started on warfarin or dabigatran 24 hours 
post TAVI if clinically safe and continued indefinitely.  If 

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clinically safe, patient’s being started on warfarin should be 
bridged with UF or LMW heparin until INR therapeutic. 
Note: Any changes to anticoagulation regimen from study visit to study visit will be noted on the CRF 
including reason for change. 
 
6.3.3.3.2 
Antibiotic Prophylaxis 
Study subjects should be treated prophylactically with antibiotics for endocarditis per the 
recommendations of the American Heart Association [43]. 
6.3.3.3.3 
Procedure Assessments 
Procedural information, findings, results, and SAPIEN XT delivery system and device 
identification will be recorded on the Case Report Form and are listed below: 
• Duration of the procedure, defined as the time from skin incision to access closure; 
• All cardiac medications and all medications given for cardiovascular effect; 
• A supra-aortic angiogram or TEE to assess valve performance and coronary patency 
• Fluoroscopic imaging of implanted valve to assess acute deployment (e.g. proper 
annular placement, fully vs. under deployed, circularity/ovality) 
• Contrast media quantity 
• Total fluoroscopy time and dose 
• Adverse events 
Subjects will be continuously monitored clinically, hemodynamically, and 
electrocardiographically during the index procedure for all local and systemic side-effects. 
It is recommended subjects are monitored in the operating room for at least 15 minutes after 
completion of the procedure, with special attention to hemodynamic condition and cardiac 
rhythm. The sheaths may be removed when ACTs reach <150 sec after implantation of the 
study valve (for non-surgical closures). 
6.3.3.4 
Post-Procedure 
Post-procedure clinical evaluations should be performed within 48 hours of the index 
procedure.  Specific assessments include the following: 
• Current cardiac medications and all medications given for cardiovascular effect 
• Adverse events 
• Neurological assessment 
o NIHSS 
o MRS  

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o CK/CK-MB and/or troponins 
o Albumin 
• 12-Lead ECG 
• Comprehensive TTE.  If not adequate, a TEE will be performed 
For patients with abnormal findings related to valve integrity and position and patients with 
adverse events related to worsening valve function, fluoroscopic imaging of the implanted valve 
will be completed.   
6.3.3.6.2 
6 Month Visit 
All patients will undergo the following assessments within the 6 Month follow-up period: 
• Adverse events 
• Current cardiac medications and all medications given for cardiovascular effect 
The 6 month visit may be completed via a telephone conversation with a delegated study team 
member.  The telephone call must be documented in the patient’s study records.  
6.3.3.6.3 
1 Year Visit 
All patients will undergo the following assessments within the 12 Month follow-up period: 
• Pertinent physical examination [include blood pressure, weight and all major systems 
findings] 
• Adverse events 
• Current cardiac medications and all medications given for cardiovascular effect 
• NYHA functional classification 
• CSS Angina Classification 
• 12-Lead ECG 
• Comprehensive TTE.  If not adequate, a TEE will be performed 
For patients with abnormal findings related to valve integrity and position and patients with 
adverse events related to worsening valve function, fluoroscopic imaging of the implanted valve 
will be completed. 
6.3.3.6.4 
2-5 Year Annual Follow-up Visit 
All patients will undergo the following assessments within the 2-5 Year annual follow-up period: 
• Pertinent physical examination [include blood pressure, weight and all major systems 
findings] 
• Adverse events 
• Current cardiac medications and all medications given for cardiovascular effect 

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• NYHA functional classification 
• CSS Angina Classification 
• Comprehensive TTE.  If not adequate, a TEE will be performed 
For patients with abnormal findings related to valve integrity and position and patients with 
adverse events related to worsening valve function, fluoroscopic imaging of the implanted valve 
will be completed. 
6.3.4 
Missed Visits 
Every patient should be encouraged to remain in the study until they have completed the 
protocol-required follow-up period. If the patient discontinues prematurely from the study, the 
reason for discontinuation must be documented on the appropriate case report form (CRF). 
Possible reasons for premature discontinuation may include, but are not limited to the 
following: 
• Withdrawal of consent: Patient decides to withdraw from the study. If a subject 
withdraws from the clinical investigation, the reason(s) should be recorded. If such 
withdrawal is due to problems related to the investigational device safety or 
performance, the investigator shall ask for the subject’s permission to follow his/her 
status/condition outside the investigation. 
• Lost to follow-up: All patients should be encouraged to return to the clinic for evaluation 
during follow-up (excluding 6 Month telephone visit).  If a patient is unable to return to 
the clinic, 3 separate telephone calls should be made to attempt to bring the patient 
back into the clinic or obtain safety information. All attempts should be documented in 
the source documents. If the patient does not respond to the 3 telephone calls then the 
Investigator should send a certified letter to the subject.  
 
6.3.5 
Study Termination 
The Sponsor has the right to discontinue a site or terminate the trial for the following reasons: 
• The Sponsor may terminate the study for safety reasons 
• A decision on the part of the Sponsor to suspend or discontinue testing, evaluation, or 
development of the product for any reason 
• The Sponsor may decide to close a study site when the Investigator fails to enroll 
patients 
• Failure of the Investigator to comply with pertinent regulations of appropriate 
regulatory authorities 
• Insufficient adherence to protocol requirements 

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• Submission of knowingly false information from the research facility to the Sponsor, the 
Sponsor’s representatives or appropriate regulatory authorities 
If the study is terminated early, all specified follow-up data on subjects enrolled prior to 
termination will be collected and reported 
6.3.6 
Standard of Care 
All enrolled patients will receive the standard of care during the clinical trial as well as following 
the conclusion of their participation. Any patients with symptoms of valve failure at any time 
throughout the study duration should undergo standard diagnostic imaging (e.g. (TTE)) to 
assess valve function. Each patient will be provided with an implant card. This implant card can 
be carried by the patient to be shown to any clinician to inform a treating physician of the 
implanted SAPIEN XT THV. Subjects that are enrolled, but not treated with the SAPIEN XT THV 
will likely be screened for alternative treatments (when available) or continue with the care 
they have been receiving to date. 
7. Study Material & Methods 
7.1 
Study Device  
The SAPIEN XT and its delivery components will have a unique product identifier.  This 
information will be recorded in the study subject’s medical file.  The Instructions for Use for the 
SAPIEN XT THV System are provided with the device.  
7.2 
Storage & Labeling 
The SAPIEN XT THV System is to be stored as specified on the unit labels.  All investigational 
stock will be stored in a secure and controlled area. 
7.3 
Device Accountability 
The Investigator shall maintain accurate records of the receipt and disposition of the 
investigational devices. A device disposition log supplied by Edwards will be used to record 
device receipt, uses, discards, or returns. Device disposition will be verified by the Sponsor 
periodically throughout the study. All unused devices shall return to Edwards, along with the 
completed device disposition log at completion of the enrolment period. The Investigator’s 
copy of the device disposition log must document the devices used in study subjects as well as 
unused devices that are returned to Edwards. Use of the SAPIEN XT THV System is prohibited 
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8. Evaluation of Safety 
8.1 
Adverse Event Assessments 
Adverse events may be volunteered by patients, elicited from questioning by Investigator or 
delegated study personnel, or collected via observation by the Investigator.  In addition, 
patients will be instructed to contact the investigator, and/or study coordinator if any 
significant adverse events (e.g., expanded safety composite events) occur between study 
evaluation visits. 
Adverse event collection begins when the patient starts the procedure.  This is defined as when 
anesthesia is first administered.     
8.1.1 
Investigator Assessment Responsibilities 
The Investigator will determine if an adverse event is serious and not related, possibly related, 
or related to the device or procedure. 
Pre-existing medical conditions or symptoms reported prior enrolment will be recorded in 
medical history form and will not be recorded as an adverse event.  In the event there is a 
worsening in the pre-existing medical condition or symptoms after enrolment, then an adverse 
event will be recorded.  
8.1.2 
Sponsor Assessment Responsibilities 
All adverse events will be reviewed by the Study Safety Officer who will determine if the 
adverse event is serious; anticipated or unanticipated; and not related, possibly related, or 
related to the device or procedure.  
8.1.3 
Medical Reviewer Responsibilities 
All endpoint related adverse events will be reviewed by a Medical Reviewer who will determine 
if the adverse event is serious; and not related, possibly related, or related to the device or 
procedure. 
8.2 
Device Deficiency 
Device deficiency is an inadequacy of a medical device with respect to its integrity, quality, 
durability, reliability, safety or performance. It includes malfunctions, user errors and 
inadequate labeling. 
Device deficiencies that did not lead to an adverse event but could have led to a medical 
occurrence: 
a) If either suitable action had not been taken, 
b) If intervention had not been made, or 
c) If circumstances had been less fortunate. 

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Reporting conventions for device deficiencies that could result in a Serious Adverse Event (SAE) 
are the same as those for an actual SAE. 
8.3 
Adverse Event Reporting 
All adverse events are reported from the start of the procedure, which is defined as when 
anesthesia is firsts administered, and are reported until subject participation has ended (i.e. 
completion of the study or withdrawal of consent).  Adverse events must be reviewed at every 
follow-up visit until resolution, AE has stabilized (according to Investigator), or the study has 
been completed.  Should the adverse event be ongoing at time of study completion, the 
database should be updated to reflect status. 
Reporting guidelines for adverse events: 
• Record the number of units of blood needed for any transfusion associated with any 
overt bleeding event 
• Failure of a percutaneous closure device shall be reported as an access site vascular 
closure device complication 
• Vascular complications shall be designated as access or non-access related; 
8.4 
SAE and USADE Reporting 
All Serious Adverse Events (SAE) and Unanticipated Serious Adverse Device Effect (USADE) must 
be reported to Edwards Lifesciences within 24 hours of the Investigator or delegated study 
personnel becoming aware of the event or according to local regulations (whatever is most 
stringent).  SAEs and USADEs will be reported to the EC and regulatory authorities as required 
by national regulations or by the EC itself. 
Information may be entered into the Case Report Form or reported directly to the Edwards 
Lifesciences, with documentation of such notification being recorded and filed.  Notifications 
and source documents will be provided to Safety Officer. 
At the time of initial notification, the following minimal information should be provided: 
• Identifiable patient: subject number 
• Identifiable reporter: study site 
• Adverse event summary 
• Causal relationship to device and procedure 
• Awareness date 
The USADE Case Report Forms should be completed within five working days.  All USADEs must 
be followed until resolution or until a stable clinical endpoint is reached.  All required 
treatments and outcomes of the USADE must be recorded.  

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Edwards will notify all participating clinical Investigators, ECs, and regulatory bodies as 
necessary of all USADEs that occur during the study within the specified reporting time frame 
following event notification.  Investigators are responsible for reviewing information received 
about USADEs.  
8.5 
Device Deficiency and Vigilance Reporting 
Device deficiencies which could have led to a serious adverse device effect should undergo the 
same reporting as serious adverse events.  They should be reported to Edwards Lifesciences 
within 24 hours of awareness and to the EC and regulatory authorities as required by 
regulations or the EC. 
Adverse device effects, device malfunctions and device failures must be reported to Edwards 
Lifesciences in accordance with the regulations and Edwards Lifesciences policies. 
The Edwards Lifesciences ‘Complaint Reporting Process’ form is available in the site study 
document file. 
8.6 
Source Documents 
The site will provide to Edwards Lifesciences a copy of anonymized supporting documentation 
(such as hospital record, laboratory results, autopsy results) of all SAES and safety related 
composite events.  
9. Risk Evaluation 
9.1 
Potential Risk to Study Subjects 
For the purposes of this study, adverse events that may be anticipated are associated with the 
use of the SAPIEN XT THV System as well as the anesthesia and interventional procedures used 
to deliver and deploy the SAPIEN XT THV. 
Anticipated risks have been minimized to the furthest extent possible, but the nature of the 
procedure and the severity of the patient’s disease state has inherent risks. Exposure to ionizing 
radiation associated with fluoroscopy, x-rays and CT is no more than is associated with routine 
clinical practice for transcatheter aortic heart valve replacement. 
Risks are outlined in the SAPIEN XT THV System Instructions for Use (IFU) 
9.2 
Methods to Minimize Risk 
Product handling and procedure guidance are provided in the Training Materials and IFU and 
will be used for device training to minimize risks associated with device use. 

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Additionally, efforts will be made to minimize these possible risks though site/investigator 
selection and management. First, site and investigator selection criteria are established to 
ensure that the study personnel and their institutions are qualified to screen, perform and 
manage the study procedures as well as support the associated requirements for research. 
Second, the trial management structure is designed to provide disciplined oversight of the trial 
activities including close monitoring of site and personnel performance and also support 
opportunities for investigators and study personnel to share best practices through investigator 
meetings, ongoing education and case reviews. 
 
9.3 
Study Site Criteria 
Site and investigator criteria include the following: 
• Interventional cardiologists must be experienced and skilled in percutaneous balloon 
valvuloplasty. 
• Strong interdepartmental collaboration between cardiac surgery and interventional 
cardiology operators will be assessed by an experienced trial study team. The study site 
team must be trained in the use of the investigational devices prior to enrollment of 
study patients. 
• The procedure setting must include a fixed C-arm angiography imaging capability in the 
catheterization lab or operative suite and/or a hybrid catheterization/operating room 
suite. 
• The study site must have an operating room. 
• The study site must have an adequately staffed research department with a minimum of 
one dedicated study coordinator. 
 
9.4 
Benefits 
Participation in the study does not guarantee any benefits.  The potential benefits resulting 
from this study fall into the following categories: 
• Direct benefit patient(s) may receive from participation in the study and being treated 
with the investigational device, 
• Possible benefit patient(s) may receive from participation in the study and being treated 
with the investigational device, 
• Possible benefit for future patient(s) receiving the SAPIEN XT THV based upon results of 
the study. 
Aortic valve replacement with the Edwards SAPIEN XT THV System may result in one or more of 
the following benefits: improved valvular function, acute alleviation of symptoms related to 

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aortic stenosis, improved quality of life in patients that may prefer or be more suitable for 
alternative treatments for aortic valve stenosis, and/or improved morbidity and mortality.  
Information gained from the conduct of this study may be of benefit to other people with the 
same medical condition in the future. Alternative treatments include palliative medical therapy, 
aortic balloon valvuloplasty and high-risk surgical replacement of the aortic valve.  
 
9.5 
Risk-Benefit Analysis 
The body of clinical evidence supporting treatment with the SAPIEN XT THV is robust, and is 
described in Section 2.2. The device design and implantation procedure for the SAPIEN XT valve 
is similar to other Edwards SAPIEN THVs. 
The relative safety of the TAVI procedure in comparison to surgical AVR in high risk patients is 
being studied in the PARTNER Cohort A, as previously described in Section 2.2. The 2-year 
outcome data from the PARTNER study demonstrate that TAVI is non-inferior to surgical AVR 
(SAVR) in terms of all-cause mortality [32]. Strokes and major vascular events were statistically 
more prevalent with TAVI, whereas major bleeding and new onset atrial fibrillation events were 
more prevalent in the AVR subjects. Both stroke and major bleeding had a significant impact on 
mortality. Major vascular complications had impact on mortality only in the TAVI arm. Although 
strokes were more frequent in the TAVI arm, those that occurred in the SAVR arm were twice 
as likely to be associated with mortality than those that occurred in the TAVI arm (hazard ratio 
= 2.76 for TAVI and 4.99 for SAVR) [49]. Major bleeding complications were not only 2 to 3 
times more frequent in the AVR arm than TAVI arm, but were also associated with a 
significantly increased 1-year mortality in the AVR arm, whereas major bleeding complications 
after TF-TAVR were not [50]. 
Benefits of TAVI over AVR include shorter hospital stay and faster resolution of symptoms of 
congestive heart failure demonstrated by greater reductions in NYHA class observed at 30 days 
[32]. Concomitant to the improvement in NYHA class, quality of life also improved significantly 
more over the first 30 days post-procedure for TAVI patients. Patients undergoing TAVI via the 
transfemoral approach demonstrated significant health status benefits with TAVI versus SAVR 
at 1 month (difference, 9.9 points; 95% confidence interval: 4.9 to 14.9; p<0.001) on the Kansas 
City Cardiomyopathy Questionnaire [30]. 
10. Definitions 
The definitions used in this protocol are consistent with those initiated with the initial set of 
standardized end-points proposed by the Valve Academic Research Consortium (VARC) [45] and 
updated in VARC-2 publication [46] as well as those used in the PARTNER clinical trials. 

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Term 
Definition 
Reference/ 
Justification 
Adverse Event (AE) 
Any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory findings) in subjects, 
users or other persons, whether or not related to the investigational 
device.  
 
ISO 14155: 
2011 
Serious Adverse Event (SAE) 
Adverse Event that:  
a) led to a death, 
b) led to a serious deterioration in the health of a study patient that  
• resulted in a life-threatening illness or injury, 
• resulted in permanent impairment of a body structure or body 
function, 
• required inpatient hospitalization or prolongation of existing 
hospitalization, 
• resulted in a medical or surgical intervention to prevent permanent 
impairment to body structure or a body function. 
c) leads to fetal distress, fetal death or a congenital abnormality or birth 
defect 
Important medical events not resulting in the above should be assessed as 
an SAE. 
Any major or clinically significant adverse event occurring during and after 
the study valve implantation or BAV procedure:  
The following is not considered an SAE: Hospitalization for diagnostic or 
elective surgical procedures, planned at or before the enrollment for a pre-
existing condition. 
 
ISO 14155: 
2011 
 
FDA (21 CFR 
312.32 (a) 
 
Adverse Device Effect (ADE) 
Adverse event related to the use of an investigational medical device.  
This definition also includes adverse events resulting from insufficient or 
inadequate instructions for use, deployment, implantation, installation, or 
operation, or any malfunction of the investigational device. And events 
resulting from use error or from intentional misuse. 
 
ISO 14155: 
2011 
Serious Adverse Device 
Effect (SADE) 
Adverse Device Effect that resulted in any of the consequences 
characteristics of a Serious Adverse Event. 
 
ISO 14155: 
2011 
Unanticipated Serious 
Adverse Device Effect 
(USADE) 
Any serious adverse effect on health or safety or any life-threatening 
problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious 
problems associated with a device that relates to the rights, safety, or 
welfare of patients. 
 
ISO 14155: 
2011 
Acute Kidney Injury 
Increase in serum creatinine (up to 7 days) compared with baseline 
Stage 1: Increase in serum creatinine to 150% to 199% (1.5 to 1.99 
increase compared with baseline) OR increase of 0.3 mg/dl (26.4 mmol/l), 
OR 
 
Urine output < 0.5ml/kg/hr for > 6 hours but < 12 hours 
Stage 2: Increase in serum creatinine to 200% to 299% (2.0 to 2.99  
increase compared with baseline), OR  
 
Urine output < 0.5ml/kg/hr for > 12 hours but < 24 hours 
Stage 3:* Increase in serum creatinine to 300% (3  increase compared with 
baseline) or serum creatinine of 4.0 mg/dl (354 mmol/l) with an acute 
increase of at least 0.5 mg/dl (44 mmol/l), OR 
 
Urine output < 0.3ml/kg/hr for ≥ 24 hours OR anuria ≥ 12 hours 
The Increase in creatinine must occur within 48 hours 
*Patients receiving renal replacement therapy are considered to meet 
Stage 3 criteria irrespective of other criteria. 
VARC-2 
Aortic Prosthetic Valve 
Dysfunction 
Prosthetic Valve Stenosis 
VARC-2 

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Term 
Definition 
Reference/ 
Justification 
Prosthetic valve regurgitation: Mean aortic valve gradient ≥20 mmHg, EOA 
≤0.9-1.1 cm2‡ and/or DVI<0.35, AND/OR moderate or severe prosthetic 
valve regurgitation* 
‡Depending on body surface area 
* Refers to VARC-2 definitions listed in this table 
Bleeding Event 
Life-threatening or Disabling Bleeding 
• Fatal bleeding (BARC Type 5),  OR 
• Bleeding in a critical area or organ, such as intracranial, intraspinal, 
intraocular, or pericardial necessitating pericardiocentesis, or 
intramuscular with compartment syndrome (BARC Type 3b or 3c), OR    
• Bleeding causing hypovolemic shock or severe hypotension requiring 
vasopressors or surgery, OR 
• Overt source of bleeding with drop in hemoglobin of ≥5 g/dL or whole 
blood of packed red blood cells (RBC) transfusion ≥4 units* (BARC type 
3b) 
Major Bleeding (BARC type 3a) 
Overt bleeding either associated with a drop in the hemoglobin level of at 
least 3.0 g/dL or requiring transfusion of 2-3 units of whole blood/RBC  
AND  
Does not meet criteria of life-threatening or disabling bleeding. 
Minor  Bleeding (BARC type 2 or 3a, depending on severity) 
Any bleeding worthy of clinical mention (e.g. access site hematoma) that 
does not qualify as life-threatening, disabling or major. 
* Given one unit of packed RBC typically will raise blood hemoglobin 
concentration by 1 g/dL, an estimated decrease in hemoglobin will be 
calculated. 
BARC = Bleeding Academic Research Consortium 
VARC-2 
 
 
 
 
 
 
 
 
  
Cardiac Tamponade (TAVI-
related) 
Evidence of a new pericardial effusion associated with hemodynamic 
instability and clearly related to the TAVI procedure 
VARC-2 
Cardiomyopathy 
A chronic disease of the myocardium in which the muscle is abnormally 
enlarged, thickened, and/or stiffened. Indicate “Yes” on the Baseline CRF if 
the patient has a documented history of cardiomyopathy. 
Cardiopulmonary Bypass, 
Unplanned Use (TAVI-
related) 
Unplanned use of CPB for hemodynamic support at any time during the 
TAVI procedure 
VARC-2 
Conduction Disturbances 
and Arrhythmias 
Up to 72 h, continuous rhythm monitoring is recommended in order to 
maximize detection of arrhythmias 
Data elements to be collected should include: 
• 
Baseline conduction abnormalities, paroxysmal or permanent atrial 
fibrillation (or flutter), and presence of permanent pacemaker*  
• 
Implant-related new or worsened cardiac conduction disturbance 
(new or worsened first degree atrioventricular (AV) block, second 
degree AV block (Mobitz I or Mobitz II), third degree AV block, 
incomplete right bundle branch block, right bundle branch block, 
intraventricular conduction delay, left bundle branch block, left 
anterior fascicular block, or left posterior fascicular block, including 
block requiring permanent pacemaker implant 
• 
Persistent or transient high degree AV block. High grade AV block is 
persistent if  it is present every time the underlying rhythm is checked 
• 
New permanent pacemaker implantation, with precision of the 
indication and number of days post-implant of placement of new 
permanent pacemaker 
• 
New-onset atrial fibrillation (or flutter)†  
• 
Any new arrhythmia resulting in hemodynamic instability or requiring 
therapy‡ 
VARC-2 

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Term 
Definition 
Reference/ 
Justification 
* Type of permanent pacemaker should be recorded (e.g. defibrillator, 
single versus dual chamber, biventricular) 
† New-onset atrial fibrillation (or flutter)* is diagnosed as any arrhythmia 
within hospitalization that has the ECG characteristics of atrial fibrillation 
(or flutter) and lasts sufficiently long to be recorded on a 12-lead ECG, or at 
least 30 seconds on a rhythm strip 
‡ Therapy includes electrical/medical cardioversion or initiation of a new 
medication (oral anticoagulation, rhythm or rate controlling therapy). 
Conversion to Open Surgery 
(TAVI-related) 
Conversion to open sternotomy during the TAVI procedure secondary to 
any procedure-related complications 
VARC-2 
Coronary obstruction (TAVI-
related) 
Angiographic or echocardiographic evidence of a new, partial or complete, 
obstruction of a coronary ostium, either by the valve prosthesis itself, the 
native leaflets, calcifications, or dissection, occurring during or after the 
TAVI procedure 
VARC-2 
Device Malfunction 
The failure of a device to meet any of its performance specifications or 
otherwise perform as intended.  Performance specifications include all 
claims made in the labeling of the device. 
ISO14155:2011 
Device Success 
Absence of procedural mortality AND  
Correct positioning of a single prosthetic heart valve into the proper 
anatomical location AND  
Intended performance of the prosthetic heart valve (no prosthesis-patient 
mismatch and mean aortic valve gradient <20 mmHg or peak velocity <3 
m/s, AND no moderate or severe prosthetic valve regurgitation*) 
*Refers to VARC definitions detailed elsewhere in this Table 
If success or failure cannot be determined due to missing or unevaluable 
echos, device success will be considered missing. 
VARC-2  
Endocarditis (Operated 
Valvular Endocarditis) 
Any one of the following: 
• The diagnosis of operated valvular endocarditis based on customary 
clinical criteria including an appropriate combination of positive blood 
cultures, clinical signs and histologic confirmation of endocarditis at 
reoperation or autopsy (using revised Duke criteria). 
• Evidence of abscess, paravalvular leak, pus, or vegetation confirmed as 
secondary to infection by histological or bacteriological studies during 
a re-operation 
• Findings of abscess, pus, or vegetation involving a repaired or replaced 
valve during an autopsy 
VARC-2 
 
Hostile Chest 
Any of the following or other reasons that make redo operation through 
sternotomy or right anterior thoracotomy prohibitively hazardous: 
• Abnormal chest wall anatomy due to severe kyphoscoliosis or other 
skeletal abnormalities (including thoracoplasty, Potts’ disease 
• Complications from prior surgery 
• Evidence of severe radiation damage (e.g. skin burns, bone 
destruction, muscle loss, lung fibrosis or esophageal stricture) 
• History of multiple recurrent pleural effusions causing internal 
adhesions 
VARC-2 
Liver Disease, 
Severe/Cirrhosis 
Any of the following: 
• Child-Pugh class C  
• MELD score ≥10 
• Portal-caval, spleno-renal, or transjugular intrahepatic portal shunt,  
• Biopsy proven cirrhosis with portal hypertension or hepatocellular 
dysfunction 
VARC-2 
Mitral Valve Apparatus 
Damage (TAVI-related) 
Angiographic or echocardiographic evidence of new damage to the mitral 
valve apparatus (chordae papillary muscle, or leaflet) during or after the 
TAVI procedure 
VARC-2 

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Term 
Definition 
Reference/ 
Justification 
Mortality 
Cardiovascular Death 
Any one of the following criteria: 
• Any death due to proximate cardiac disease cause (e.g. myocardial 
infarction, cardiac tamponade, worsening heart failure); 
• Death caused by non-coronary vascular conditions such as 
cerebrovascular disease, pulmonary embolism, ruptured aortic 
aneurysm, or other vascular disease. 
• All procedure-related deaths, including those related to a complication 
of the procedure or treatment for a complication of the procedure; 
• All valve-related including structural or nonstructural valve dysfunction 
or other valve-related adverse events 
• Sudden or unwitnessed death  
• Death of unknown cause 
Non-Cardiovascular Death 
Any death in which the primary cause of death is clearly related to another 
condition (e.g. trauma, cancer, suicide) 
VARC-2 
Myocardial Infarction 
Peri-Procedural MI (≤72 hours of the index procedure): 
1. New ischemic symptoms (e.g. chest pain or shortness of breath),new 
ischemic signs (e.g. ventricular arrhythmias, new or worsening heart 
failure, new ST-segment changes,  hemodynamic instability, new 
pathological Q waves in at least 2 contiguous leads, imaging evidence 
of new loss of viable myocardium or new wall motion abnormality)   
AND 
2. Elevated cardiac biomarkers (preferably CK-MB) within 72 hours after 
the index procedure, consisting of at least one sample post-procedure 
with a peak value exceeding 15x upper reference limit (troponin) or 5x 
for CK-MB. If cardiac biomarkers are increased at baseline (>99th 
percentile), a further increase of at least 50% post-procedure is 
required AND the peak value must exceed the previously stated limit. 
Spontaneous MI (>72 h after the index procedure): 
Any one of the following criteria: 
• Detection of rise and/or fall of cardiac biomarkers (preferably 
troponin) with at least one value above the 99th percentile URL, 
together with evidence of myocardial ischemia with at least one of 
the following: 
o Symptoms of ischemia 
o ECG changes indicative of new ischemia [new ST-T changes or 
new left bundle branch block [LBBB]); 
o New  pathological Q waves in at least 2 contiguous leads; 
o Imaging evidence of new loss of viable myocardium or new 
regional wall motion abnormality. 
Sudden, unexpected cardiac death, involving cardiac arrest, often with 
symptoms suggestive of myocardial ischemia, and accompanied by 
presumably new ST elevation, or new LBBB, and/or evidence of fresh 
thrombus by coronary angiography and/or at autopsy, but death occurring 
before blood samples could be obtained, or at a time before the 
appearance of cardiac biomarkers in the blood. 
Pathological findings of an acute myocardial infarction.  
VARC-2 
New York Heart Association 
Classification (NYHA) 
Class I:  Patients with cardiac disease but without resulting limitations of 
physical activity.  
Class II: Patients with cardiac disease resulting in slight limitation of 
physical activity.  Patients are comfortable at rest.  Ordinary physical 
activity results in fatigue, palpitation, dyspnea, or anginal pain. 
New York 
Heart 
Association 

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Term 
Definition 
Reference/ 
Justification 
Class III: Patients with cardiac disease resulting in marked limitation of 
physical activity.  They are comfortable at rest.  Less than ordinary physical 
activity causes fatigue, palpitation dyspnea, or anginal pain. 
Class IV:Patients with cardiac disease resulting in inability to carry on any 
physical activity without discomfort.  Symptoms of cardiac insufficiency or 
of the anginal syndrome may be present even at rest.  If any physical 
activity is undertaken, discomfort is increased. 
Paravalvular Leak (See Also 
“Nonstructural Dysfunction”) 
See “ Aortic Valve (Prosthesis) Regurgitation”  
VARC-2 
Porcelain Aorta 
Heavy circumferential calcification of the entire ascending aorta extending 
to the arch such that cross-clamping is not feasible.   
VARC-2 
Pulmonary Hypertension, 
Severe 
Right Ventricular 
Dysfunction, Severe 
Primary or secondary pulmonary hypertension with PA systolic pressures 
greater than 2/3 of systemic pressure 
VARC-2 
Stroke and Transient 
Ischemic Attack (TIA) 
Diagnostic Criteria: 
Acute episode of a focal or global neurological deficit with at least one of 
the following: 
• Change in level of consciousness 
• Hemiplegia 
• Hemiparesis 
• Numbness or sensory loss affecting one side of the body 
• Dysphasia or Aphasia 
• Hemianopia  
• Amaurosis fugax  
• Other new neurological sign(s)/symptom(s) consistent with stroke 
Stroke: Duration of a focal or global neurological deficit ≥ 24 hours OR  
< 24 hours if available neuroimaging documents a new hemorrhage or 
infarct; OR the neurological deficit results in death. 
Transient Ischemic Attack (TIA): Duration of a focal or global neurological 
deficit < 24 hours; any variable neuroimaging does no demonstrate a new 
hemorrhage or infarct.  
No other readily identifiable non-stroke cause for the clinical presentation 
(e.g., brain tumor, trauma, infection, hypoglycemia, peripheral lesion, 
pharmacological  influences) to be determined by or in conjunction with 
designated neurologist* 
Confirmation of the diagnosis by at least one of the following: 
• Neurology or neurosurgical specialist 
• Neuroimaging procedure (CT or brain MRI), but stroke may be 
diagnosed on clinical grounds alone. 
*Patients with non-focal global encephalopathy will not be reported as a 
stroke without unequivocal evidence of cerebral infarction based upon 
neuroimaging studies (CT scan or brain MRI).  
VARC-2  
Stroke Classifications 
Ischemic – An acute episode of focal cerebral, spinal, or retinal dysfunction 
caused by infarction of central nervous 
system tissue 
Hemorrhagic – An acute episode of focal or global cerebral or spinal 
dysfunction caused by intraparenchymal, intraventricular, or subarachnoid 
hemorrhage 
A stroke may be classified as undetermined if there is insufficient 
information to allow categorization as ischemic or hemorrhagic 
VARC-2 
Structural Valvular 
Deterioration (SVD) 
See: “Time-Related Valve Safety” 
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Term 
Definition 
Reference/ 
Justification 
Transcatheter Aortic Valve in 
Transcatheter Aortic Valve 
(TAV-TAV) 
 An additional valve prosthesis is implanted within a previously implanted 
prosthesis because of suboptimal device position and/or function, during 
or after the index procedure. 
VARC-2 
Valve Malpositioning 
Valve migration 
After initial correct positioning, the valve prosthesis moves upward or 
downward, within the aortic annulus from its initial position, with or 
without consequences 
Valve embolization 
The valve prosthesis moves during or after deployment such that it loses 
contact with the aortic annulus 
Ectopic valve deployment 
Permanent deployment of the valve prosthesis in a location other than the 
aortic root 
VARC-2 
Valve-Related Mortality 
See: “Mortality” 
VARC-2 
Valve Thrombosis 
Any thrombus attached to or near an implanted valve that occludes part of 
the blood flow path, interferes with valve function, or is sufficiently large 
to warrant treatment. Note that valve-associated thrombus identified at 
autopsy in a patient whose cause of death was not valve-related or at 
operation for an unrelated indication should not be reported as valve 
thrombosis 
VARC-2 
Vascular Access Site and 
Access- Related 
Complications 
Major Vascular Complications: 
• 
Any aortic dissection, aortic rupture, annulus rupture, left ventricle 
perforation, or new apical aneurysm/pseudo-aneurysm OR 
• 
Access site or access-related vascular injury (dissection, stenosis, 
perforation, rupture, arterio-venous fistula, pseudoaneurysm, 
hematoma, irreversible nerve injury, compartment syndrome, 
percutaneous closure device failure) leading to death, life-threatening 
or major bleeding*, visceral ischemia or neurological impairment OR 
• 
Distal embolization (non-cerebral) from a vascular source requiring 
surgery or resulting in amputation or irreversible end-organ damage 
OR 
• 
The use of unplanned endovascular or surgical intervention associated 
with death, major bleeding, visceral ischemia or neurological 
impairment OR 
• 
Any new ipsilateral lower extremity ischemia documented by patient 
symptoms, physical exam, and/or decreased or absent blood flow on 
lower extremity angiogram OR 
• 
Surgery for access site-related nerve injury OR 
• 
Permanent access site-related nerve injury OR 
Minor Vascular Complications: 
• Access site or access-related vascular injury (dissection, stenosis, 
perforation, rupture, arterio-venous fistula, pseudoaneuysms, 
hematomas, percutaneous closure device failure) not leading to death, 
life-threatening or major bleeding*, visceral ischemia or neurological 
impairment OR 
• Distal embolization treated with embolectomy and/or thrombectomy 
and not resulting in amputation or irreversible end-organ damage OR 
• Any unplanned endovascular stenting or unplanned surgical 
intervention not meeting the criteria for a major vascular complication 
OR 
• Vascular repair or the need for vascular repair (via surgery, ultrasound-
guided compression, transcatheter embolization, or stent-graft) OR 
Percutaneous closure device failure 
VARC-2  

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Term 
Definition 
Reference/ 
Justification 
• Failure of a closure device to achieve hemostasis at the arteriotomy 
site leading to alternative treatment (other than manual compression 
or adjunctive endovascular ballooning) 
*Refers to VARC bleeding definitions 
Ventricular Septal 
Perforation (TAVI-related) 
Angiographic or echocardiographic evidence of a new septal perforation 
during or after the TAVI procedure 
VARC-2 
Note: The Valve Academic Research Consortium (VARC) consists of representatives from several independent Academic 
Research Organizations (Cardialysis, Rotterdam, the Netherlands, Cardiovascular Research Foundation, New York City, NY, 
Duke Clinical Research Institute, Durham, NC, and Harvard Clinical Research Institute, Boston, MA), several Surgery and 
Cardiology Societies (American Association of Thoracic Surgeons, American College of Cardiology, American Heart Association, 
European Association of CardioThoracic Surgeons, European Society of Cardiology, Society of Cardiac Angiography and 
Intervention, and Society of Thoracic Surgeons) and several independent expert scientists and consultants.  
 
11. Statistical Considerations 
The clinical study is a single-arm prospective study intended to demonstrate the safety and 
performance of the SAPIEN XT THV in the Chinese population. The sample size was determined 
based on the regulatory requirement and includes the following considerations: 
11.1 
Sample Size 
The sample size of 50-60 patients is determined per Chinese regulatory requirements and 
agreement for a regional study of a medical device already approved in other regions based on 
a well-designed prospective study. 
11.2 
Timing 
Study subjects will undergo screening and pre-procedure visits, and then follow-up visits at 
Discharge, and 30 Days (+14 days) for Endpoint analysis.  Long-term follow-up data is collected 
at 6 Months (+/- 30 days), 1 Year (+/- 60 days), 2 Years (+/- 60 days), 3 Years (+/- 60 days), 4 
Years (+/- 60 days), and 5 Years (+/- 60 days). 
11.3 
Analysis Sets 
• As Treated (AT) Population: all patients that were enrolled in the trial for whom the 
SAPIEN XT valve implant procedure was begun, defined as the time in which the first 
Edwards’ investigational device is inserted into the patient. 
• Valve Implant (VI) Population: all AT patient who received and retained the SAPIEN XT 
valve upon leaving the procedure room 
All patients documented as part of the roll-in patient strategy will not be included in analysis 
population and evaluated separately.  
The primary and secondary endpoints will be reported based on the AT Population. AT patients 
that did not receive the SAPIEN XT valve will be censored at 30 days or at resolution of any AE.  

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Descriptive and summary statistical analysis will be performed on all endpoints. Patient listings 
for adverse events, deaths, and reinterventions will include all enrolled patients.   
 
11.4 
Missing Data 
All possible steps will be taken to minimize missing data in the study, including monitoring of 
data forms for completeness and efforts to track and maintain contact with study subjects 
during the follow-up period. 
 
11.5 
Endpoint Analysis 
Patient data listings and tabular and graphical presentations of results will be provided. All 
clinically relevant baseline and follow-up variables will be tabulated. Descriptive statistics will 
be used for continuous variables (e.g., mean, standard deviation, sample size, minimum, and 
maximum) and frequency tables or proportions for discrete variables. 
 
Kaplan Meier estimates will be performed at the pre-specified follow-up times to project the 
estimates for time-related safety endpoints. The Kaplan-Meier analysis will be used to compute 
the 30-day mortality rate, the primary endpoint; the standard error and confidence limits will 
be computed using Greenwood’s algorithm. 
 
Echocardiographic data will be analyzed by an Echo core laboratory with respect to the degree 
of total aortic valve regurgitation (TVR) and paravalvular aortic valve regurgitation (PAR) 
according to the VARC-2 definitions [46]. 
 
 These data and other categorical data (e.g., NYHA class) will also be presented as shift from 
baseline for each of the pre-specified follow-up periods. 
 
More specific information regarding the statistical analysis will be presented in the Statistical 
Analysis Plan (SAP). 
12. Study Administration 
12.1 
General Study Organization 
Edwards Lifesciences is the Study Sponsor, and has the overall responsibility for the conduct of 
the study, including assurance that the study meets the regulatory requirements of the 
appropriate regulatory bodies.  Edwards Lifesciences will have certain direct responsibilities and 
will coordinate other responsibilities to the specified committees, Echo core lab and other 
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Edwards Lifesciences will be responsible for submitting the Clinical Investigation Plan and all 
changes to it to the regulatory body and local EC to obtain ongoing approvals as needed. 
Edwards Lifesciences will submit all reports required by the appropriate regulatory authorities 
as identified in this section of the regulation. This may include unanticipated and serious 
adverse device effects, withdrawal of EC approval, current investigators list, annual progress 
reports, recall information, final reports and protocol violations. 
 
Edwards Lifesciences and Core Laboratories will maintain copies of correspondence, data, 
shipment of devices, adverse device effects and other records related to the study as 
appropriate. 
12.2 
Medical Reviewers 
Medical Reviewers will review and classify adverse events in accordance with the study 
protocol.   
12.3 
Echocardiography Core Laboratory 
A Core laboratory will be established for Echocardiography endpoint analysis.  Standardized 
protocols for acquiring and transmitting electronic records will be developed and documented 
prior to study initiation.   
Clinical Sites will upload a qualifying echocardiography prior to the enrolment of the first 
subject in accordance with the standardized protocol. 
Edwards Lifesciences will review echocardiography data for the duration of the study. 
12.4 
Clinical Sites 
Edwards Lifesciences will select qualified investigators, ship devices only to participating 
investigators, obtain a signed Clinical Study Agreement and provide the investigators with the 
information and training necessary to conduct the study. Edwards Lifesciences will retain copies 
of all study-related correspondence with study sites. 
 
12.5 
Site Training 
Clinical sites will be chosen that have proper facilities in place to complete THV procedures. 
Additional training of appropriate clinical site personnel will be the responsibility of the 
Sponsor. To ensure proper device usage, uniform data collection, and protocol compliance, the 
Sponsor will present a formal training session to study site personnel which will review the 
instructions for use of the device, the Investigational Plan, techniques for the identification of 
eligible patients, instructions on in-hospital data collection, CT recommendations, 
echocardiography data collection for core laboratory analysis, methods for soliciting data from 

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alternative sources, schedules for follow-up with the study site coordinators, and regulatory 
requirements. Detailed feedback regarding completion of forms will be provided by the 
Sponsor, and through regular site monitoring. Edwards Lifesciences reserves the right to 
enforce retraining for sites who have demonstrated study or procedure compliance issues. 
 
12.6 
Study Monitoring 
Edwards Lifesciences will contract with a Clinical Research Organization (CRO) to provide a 
CRA(s) to monitor the study sites to ensure that all investigators are in compliance with the 
protocol and the Investigator’s Agreement, and that all study subjects have been properly 
consented with the current version of the informed consent document. Edwards Lifesciences 
will evaluate circumstances where an investigator deviates from the clinical protocol and will 
retain the right to remove either the investigator or the investigational site from the study. 
Routine on-site monitoring visits shall include verification of the following: 
• Compliance with the protocol, any subsequent amendment(s), GCP and maintenance of 
regulatory and EC requirements.  Deviations shall be discussed with the Investigator(s) 
or delegated personnel, documented and reported 
• Only authorized and delegated individuals are participating in the study 
• The SAPIEN XT THV System is being used according to the protocol and IFU 
• Study Site resources, equipment and study personnel, remain adequate throughout the 
duration of the study 
• Patient Informed Consent is completed in accordance to the protocol and regulations 
• Only Patient Informed Consents Forms approved by the EC are used appropriately 
• Source documents and other clinical records are accurate, complete up to date, stored 
and maintained properly 
• CRFs and queries are complete, recorded in a timely manner, and consistent with source 
documents  
• All adverse events and device deficiencies are reported to Edwards without unjustified 
delay 
• All serious adverse events and deviations are reported to the EC, if required 
• All other required reports, notifications, applications, submissions and correspondence 
are maintained in the investigator's files and are accurate, complete, timely, legible, 
dated and identify the clinical investigation 
• Current laboratory normal values, laboratory certifications, accreditations, or other 
validations are present in the investigator's file 
• Subject withdrawal has been documented; the monitor shall discuss this with the 
principal investigator or his/her authorized designee 

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• Subject non-compliance with the requirements stated in the informed consent has been 
documented; the monitor shall discuss this with the principal investigator or his/her 
authorized designee 
• Suitability of the attempts to contact lost to follow-up patients and any intermediaries 
• The principal investigator and investigation site team are informed and knowledgeable 
of all relevant document updates concerning the clinical investigation 
• Any corrective and preventive actions, as needed, have been implemented and are 
effective. 
Monitors shall be appropriately qualified per the following requirements: 
• Qualified in the field of the applicable regulations and GCP through training and 
experience as well as scientific or clinical knowledge; 
• Knowledgeable on the use of the investigational device(s) and relevant requirements, 
protocol and informed consent process; 
• Trained on the Edwards' clinical quality assurance and quality control system 
All monitoring activities shall be documented in a written report. The frequency of monitoring 
visits will depend on enrollment and center compliance, but each center will at least be visited 
once per year. Further details are laid out in the monitoring plan. 
 
Edwards Lifesciences will review significant new information, including unanticipated adverse 
events and ensure that such information is provided to the study investigators and to all 
reviewing ECs and regulatory agencies as necessary.  Efforts will be made to ensure that data 
collection compliance is monitored and communicated to the Investigators in a timely manner 
throughout the trial. 
 
12.7 
Data Collection and Quality Assurance 
Data will be captured and managed through an electronic data capture (EDC) system. 
Passwords will be issued to appropriate data management personnel to ensure confidentiality 
and protection of the data by allowing variable levels of access to the computer system. 
Electronic CRFs (eCRFs) will be used to collect all patient data during the trial. eCRFs must be 
fully completed for each patient, and signed electronically by the investigator and/or designee. 
The investigator, or an individual designated by him/her, is responsible for recording all data 
from the trial onto the eCRFs on a dedicated website. The investigator is required to provide an 
electronic signature on the appropriate eCRF pages to verify that he/she has reviewed the 
recorded data. 
Completed eCRFs will be reviewed at the investigational site and remotely by authorized 
Edwards Lifesciences personnel at regular intervals throughout the trial. All eCRFs will be 

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tracked at Edwards Lifesciences and missing or unclear data will be requested as necessary 
throughout the trial.  
12.8 
Publication Policy 
Clinical sites have the right, consistent with academic standards, to publish their individual 
registry results provided such publication does not constitute a violation of the Study 
Agreement. The site agrees to submit any proposed submission for publication to Edwards 
Lifesciences for review and approval before any submission. Consent cannot be denied without 
a sensible reason.  
The results of the clinical investigation will be submitted, whether positive or negative for 
publication. The publication policy will be part of Study Agreement.   
13. Ethical Review and Consideration 
13.1 
Confidentiality 
All information and data sent to the data management center concerning patients or their 
participation in this trial will be considered confidential.  Only authorized data management 
center personnel will have access to these confidential files.  Authorized personnel from 
Edwards Lifesciences and its contractors and regulatory authorities have the right to inspect 
and copy all records pertinent to this trial.  All data used in the analysis and reporting of this 
evaluation will be without identifiable reference to the patient. 
13.2 
Records and Reports 
13.2.1 
Records 
All records related to the study and qualifications of site personnel must be kept on file and 
available for review.  These documents may include but are not limited to: 
• Clinical trial investigational plan and all amendments, all approved versions 
• Signed clinical trial agreement 
• EC approval letter, including final informed consent 
• EC membership list 
• Correspondence relating to the trial 
• CVs for all investigators and research coordinator 
• Site personnel signature list 
• Clinical monitor sign-in log 
• Patient screening/enrollment log 
• Lab certification and lab test normal ranges 
• Reports (includes annual reports, final reports from investigator and sponsor) 

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All records related to the patients’ consent and study data must be maintained for each patient 
enrolled in the trial.  These records include and are not limited to: 
• Signed Patient Informed Consent Form (latest approved site version) 
• All completed eCRFs 
• Supporting documentation of any complications and/or safety events. 
Edwards Lifesciences requests that the investigator retain copies of procedure reports, 
procedure nursing notes and the results of any interventional procedures that occurs post trial 
procedure.  Edwards Lifesciences reserves the right to secure data clarification and additional 
medical documentation on patients enrolled in this trial. 
 
13.2.2 
Deviations from Protocol 
The investigator will not deviate from the protocol without the prior written approval of 
Edwards Lifesciences except in medical emergencies or in unforeseen, isolated instances where 
minor changes are made that will not increase the patient’s risk or affect the validity of the trial.  
In medical emergencies, prior approval for protocol deviations will not be required, but the 
Edwards Lifesciences clinical research personnel must be notified within 24 hours of the 
incident.  
All protocol deviations need to be recorded in the respective section of the eCRF and reported 
according national and ethics committee requirements. Periodic monitoring of protocol 
compliance will be performed for each site. The sponsor maintains the right to place a 
moratorium on enrollment in sites deemed to have excessive protocol compliance issues.  A 
major protocol violation is the instance where a deviation significantly affects the integrity of 
the study and guidelines for Good Clinical Practice, such as when there is failure to obtain 
informed consent or violation of inclusion/exclusion criteria. In cases of major protocol 
violation, the principal investigator is required to make a written statement attesting to 
retraining or other action(s) to be taken at his/her site to avoid such violations in the future. 
13.2.3 
Record Retention Policy 
All clinical sites will maintain study records for a minimum of 15 years after marketing approval 
is obtained.  After 15 years, clinical sites should following hospital and regulatory guidelines for 
record retention.  Record retention dates will be provided to all parties concerned by Edwards 
Lifesciences. 
14. Financial and Insurance Considerations 
14.1 
Clinical Trial Funding  
As the Sponsor, Edwards Lifesciences will fund the duration of the trial.   

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14.2 
Clinical Trial Insurance  
As required by local/country regulation, Edwards Lifesciences will obtain clinical trial insurance 
for the duration of the clinical trial and provide evidence of coverage. 
15. References 
1. 
Bonow, R.O., et al., ACC/AHA 2006 guidelines for the management of patients with 
valvular heart disease: a report of the American College of Cardiology/American Heart 
Association Task Force on Practice Guidelines (writing Committee to Revise the 1998 
guidelines for the management of patients with valvular heart disease) developed in 
collaboration with the Society of Cardiovascular Anesthesiologists endorsed by the Society 
for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. J 
Am Coll Cardiol, 2006. 48(3): p. e1-148.  
2. 
Frank, S., A. Johnson, and J. Ross, Jr., Natural history of valvular aortic stenosis. Br Heart J, 
1973. 35(1): p. 41-6.  
3. 
Gardin, J.M., et al., Aortic stenosis: can severity be reliably estimated noninvasively? 
Chest, 1980. 77(2): p. 130-1.  
4. 
Murakami, T., et al., Changes in patterns of left ventricular hypertrophy after aortic valve 
replacement for aortic stenosis and regurgitation with St. Jude Medical cardiac valves. 
Artif Organs, 2000. 24(12): p. 953-8.  
5. 
Korfer, R., et al., Left ventricular function in heart valve surgery: a multidisciplinary 
challenge. J Heart Valve Dis, 1995. 4 Suppl 2: p. S194-7.  
6. 
Bach, D.S., et al., Evaluation of patients with severe symptomatic aortic stenosis who do 
not undergo aortic valve replacement: the potential role of subjectively overestimated 
operative risk. Circ Cardiovasc Qual Outcomes, 2009. 2(6): p. 533-9.  
7. 
Kapadia, S.R., et al., Lessons learned from balloon aortic valvuloplasty experience from the 
pre-transcatheter aortic valve implantation era. J Interv Cardiol, 2010. 23(5): p. 499-508.  
8. 
Bach, D.S., N. Cimino, and G.M. Deeb, Unoperated patients with severe aortic stenosis. J 
Am Coll Cardiol, 2007. 50(20): p. 2018-9.  
9. 
Connolly, H.M., et al., Severe aortic stenosis with low transvalvular gradient and severe 
left ventricular dysfunction:result of aortic valve replacement in 52 patients. Circulation, 
2000. 101(16): p. 1940-6.  
10. 
Bouma, B.J., et al., To operate or not on elderly patients with aortic stenosis: the decision 
and its consequences. Heart, 1999. 82(2): p. 143-8.  
11. 
Brown, J.M., et al., Isolated aortic valve replacement in North America comprising 108,687 
patients in 10 years: changes in risks, valve types, and outcomes in the Society of Thoracic 
Surgeons National Database. J Thorac Cardiovasc Surg, 2009. 137(1): p. 82-90.  
12. 
Rankin, J.S., et al., Determinants of operative mortality in valvular heart surgery. J Thorac 
Cardiovasc Surg, 2006. 131(3): p. 547-57.  

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7 February 2017, Version 2.0  
 
    
 
 
 
               Page 51 of 53                                 
13. 
Chiappini, B., et al., Outcome after aortic valve replacement in octogenarians. Ann Thorac 
Surg, 2004. 78(1): p. 85-9.  
14. 
Thourani, V.H., et al., Outcomes of surgical aortic valve replacement in high-risk patients: 
a multiinstitutional study. Ann Thorac Surg, 2011. 91(1): p. 49-55; discussion 55-6.  
15. 
Thourani, V.H., et al., Long-term outcomes after isolated aortic valve replacement in 
octogenarians: a modern perspective. Ann Thorac Surg, 2008. 86(5): p. 1458-64; 
discussion 1464-5.  
16. 
Cribier, A., et al., Percutaneous transcatheter implantation of an aortic valve prosthesis for 
calcific aortic stenosis: first human case description. Circulation, 2002. 106(24): p. 3006-8.  
17. 
Thomas, M. and O. Wendler, Transcatheter aortic valve implantation (TAVI): how to 
interpret the data and what data is required? EuroIntervention, 2009. 5(1): p. 25-7. 
18. 
Grube, E., et al., Percutaneous aortic valve replacement for severe aortic stenosis in high-
risk patients using the second- and current third-generation self-expanding CoreValve 
prosthesis: device success and 30-day clinical outcome. J Am Coll Cardiol, 2007. 50(1): p. 
69-76.  
19. 
Kapadia, S.R., et al., Long-Term Outcomes of Inoperable Patients with Aortic Stenosis 
Randomized to Transcatheter Aortic Valve Replacement or Standard Therapy. Circulation, 
2014. 130: p. 1483-1492  
20. 
Kodali, S.K., et al., Early and late (one year) outcomes following transcatheter aortic valve 
implantation in patients with severe aortic stenosis (from the United States REVIVAL trial). 
Am J Cardiol, 2011. 107(7): p. 1058-64.  
21. 
Kodali, S.K., et al., Two-year outcomes after transcatheter or surgical aortic-valve 
replacement. N Engl J Med, 2012. 366(18): p. 1686-95.  
22. 
Lefevre, T., et al., One year follow-up of the multi-centre European PARTNER transcatheter 
heart valve study. Eur Heart J, 2011. 32(2): p. 148-57.  
23. 
Leon, M.B. Update from the PARTNER I and PARTNER II Trials in PCR London Valves. 2013. 
London, UK.  
24. 
Leon, M.B., et al., Transcatheter aortic-valve implantation for aortic stenosis in patients 
who cannot undergo surgery. N Engl J Med, 2010. 363(17): p. 1597-607.  
25. 
Makkar, R.R., et al., Transcatheter aortic-valve replacement for inoperable severe aortic 
stenosis. N Engl J Med, 2012. 366(18): p. 1696-704.  
26. 
Sack, S. The PREVAIL XT (TF and TA) Registries. in Transcatheter Cardiovasular 
Therapeutics 2012. Miami, FL.  
27. 
Sawa, Y., et al., Clinical efficacy of transcatheter aortic valve replacement for severe aortic 
stenosis in high-risk patients: the PREVAIL JAPAN trial. Surg Today, 2014.  
28. 
Svensson, L.G., et al., A comprehensive review of the PARTNER trial. J Thorac Cardiovasc 
Surg, 2013. 145(3 Suppl): p. S11-6.  

2015-06: SAPIEN XT Chinese Pre-Market Study  
Edwards Lifesciences 
7 February 2017, Version 2.0  
 
    
 
 
 
               Page 52 of 53                                 
29. 
Thomas, M. Update from the Edwards SOURCE Registries. in Transcatheter Valve 
Therapies 2013. Vancouver.  
30. 
Thomas, M., et al., One-year outcomes of cohort 1 in the Edwards SAPIEN Aortic 
Bioprosthesis European Outcome (SOURCE) registry: the European registry of 
transcatheter aortic valve implantation using the Edwards SAPIEN valve. Circulation, 
2011. 124(4): p. 425-33.  
31. 
Walters, D.L., et al., Initial experience with the balloon expandable Edwards-SAPIEN 
Transcatheter Heart Valve in Australia and New Zealand: the SOURCE ANZ registry: 
outcomes at 30 days and one year. Int J Cardiol, 2014. 170(3): p. 406-12.  
32. 
Walther, T., et al., One-year interim follow-up results of the TRAVERCE trial: the initial 
feasibility study for trans-apical aortic-valve implantation. Eur J Cardiothorac Surg, 2011. 
39(4): p. 532-7.  
33. 
Webb, J.G. 30-day Outcomes from the SAPIEN 3 Trial in EuroPCR. 2014. Paris, France.  
34. 
Windecker, S. One-Year Outcomes from The SOURCE XT Post Approval Study. in EuroPCR. 
2013. Paris, France.  
35. 
Reynolds, M.R., et al., Health-related quality of life after transcatheter aortic valve 
replacement in inoperable patients with severe aortic stenosis. Circulation, 2011. 124(18): 
p. 1964-72.  
36. 
Kapadia, S. Five-year outcomes of transcatheter aortic valve replacement in "inoperable" 
patients with severe aortic stenosis: The PARTNER Trial in Trancatheter Cardiovascular 
Therapeutics 2014. Washington, DC.  
37. 
Smith, C.R., et al., Transcatheter versus surgical aortic-valve replacement in high-risk 
patients. N Engl J Med, 2011. 364(23): p. 2187-98. 
38. 
Thourani, V.H. Three-year outcomes after transcatheter or surgical aortic valve 
replacement in high-risk patients with severe aortic stenosis in American College of 
Cardiology Scientific Sessions. 2013. San Francisco, CA.  
39. 
Windecker, S. Two-year outcomes from the SOURCE XT post approval study. in EuroPCR. 
2014. Paris, France. 
40. 
Finsterer, J. and C. Stollberger, Strategies for primary and secondary stroke prevention in 
atrial fibrillation. Neth J Med, 2008. 66(8): p. 327-33. 
41. 
Specialized Committee on Structural Heart Disease, Chinese Expert Consensus on 
Transcatheter Aortic Valve Replacement. Chin J Intervent Cardiol, 2015. 23(12): p. 661-71. 
42. 
Sievers, H., et al., A classification system for the bicuspid aortic valve from 304 surgical 
specimens. J Thorac Cardiovasc Surg, 2007. 133(5): p. 1226-33. 
43. 
Nishimura, R.A., et al., 2014 AHA/ACC Guideline for the Management of Patients With 
Valvular Heart Disease: executive summary: a report of the American College of 
Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation, 
2014. 129(23): p. 2440-92. 
44. 
Habib, G., et al., Guidelines on the prevention, diagnosis, and treatment of infective 
endocarditis (new version 2009): the Task Force on the Prevention, Diagnosis, and 

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7 February 2017, Version 2.0  
 
    
 
 
 
               Page 53 of 53                                 
Treatment of Infective Endocarditis of the European Society of Cardiology (ESC). Eur Heart 
J, 2009, 30(19): p2369-413 
45. 
Leon, M., et al., Standardized Endpoint Definitions for Transcatheter Aortic Valve 
Implantation Clinical Trials A Consensus Report From the Valve Academic Research 
Consortium. J Amer Col Card, 2011. 57(1): p.253-69 
46. 
Kappetein, A., et al., Updated Standardized Endpoint Definitions for Transcatheter Aortic 
Valve Implantation Clinical Trials A Consensus Report From the Valve Academic Research 
Consortium-2 Consensus Document. J Amer Col Card, 2012. 60(15): p.1438-54 
47. 
Comparison of 12 risk stratification schemes to predict stroke in patients with nonvalvular 
atrial fibrillation. Stroke, 2008. 39(6): p. 1901-10. 
48. 
Independent predictors of stroke in patients with atrial fibrillation: a systematic review. 
Neurology, 2007. 69(6): p. 546-54. 
49. 
Roten, L., et al., Incidence and predictors of atrioventricular conduction impairment after 
transcatheter aortic valve implantation. Am J Cardiol, 2010. 106(10): p. 1473-80. 
50. 
Genereux, P., et al., Bleeding complications after surgical aortic valve replacement 
compared with transcatheter aortic valve replacement: insights from the PARTNER I Trial 
(Placement of Aortic Transcatheter Valve). J Am Coll Cardiol, 2014. 63(11): p.1100-9.