A Prospective, Single-arm, Controlled, Multicenter Study to Establish the Safety and Effectiveness of the CENTERA THV System in Intermediate Risk Patients Who Have Symptomatic, Severe, Calcific, Aortic Stenosis Requiring Aortic Valve Replacement
Phase: NA
Conditions: Aortic Valve Stenosis
Sponsor: Edwards Lifesciences

 
 
 
 
ExCEED: 
A Prospective, Single-arm, Controlled, Multicenter Study to 
Establish the Safety and Effectiveness of the CENTERA THV 
System in IntermEDiate Risk Patients who have Symptomatic, 
Severe, Calcific, Aortic Stenosis Requiring Aortic Valve 
Replacement 
 
 
 
 
NCT03517436 
 
 
 
July 29, 2021 

PROPRIETARY DATA: This document and the information contained herein may not be reproduced, used or 
disclosed without written permission from Edwards Lifesciences LLC. 
Edwards, Edwards Lifesciences, the stylized E logo, Edwards CENTERA, CENTERA, Edwards SAPIEN, SAPIEN, 
Edwards SAPIEN XT, SAPIEN XT, Edwards SAPIEN 3, SAPIEN 3 and eSheath, are trademarks of Edwards 
Lifesciences Corporation. 
 
 
 
 
ExCEED: 
A Prospective, Single-arm, Controlled, Multicenter Study to 
Establish the Safety and Effectiveness of the CENTERA THV 
System in IntermEDiate Risk Patients who have Symptomatic, 
Severe, Calcific, Aortic Stenosis Requiring Aortic Valve 
Replacement 
 
 
Clinical Protocol 
Study Number:  2017-18 
Version 2.0 
July 29, 2021 
 
 
 
Study Sponsor: 
Edwards Lifesciences LLC 
One Edwards Way 
Irvine, CA  92614 
USA 
 
 

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TABLE OF CONTENTS 
LIST OF TABLES ...................................................................................................................... 4 
PROTOCOL SYNOPSIS ........................................................................................................... 5 
INVESTIGATOR SIGNATURE PAGE ....................................................................................... 9 
1 
INTRODUCTION ...............................................................................................................10 
 
AORTIC STENOSIS ........................................................................................................10 
 
TREATMENT OF AS .......................................................................................................10 
 
TAVR vs. SAVR ..................................................................................................................... 11 
 
CENTERA THV CLINICAL HISTORY ..............................................................................12 
 
CENTERA Study #2014-03 ................................................................................................... 13 
 
CENTERA Study #2012-03 ................................................................................................... 22 
 
CENTERA Study #2010-08 ................................................................................................... 23 
2 
STUDY OBJECTIVE .........................................................................................................24 
3 
STUDY DESIGN ................................................................................................................24 
4 
STUDY DEVICES ..............................................................................................................24 
 
CENTERA THV ..........................................................................................................25 
 
CENTERA DELIVERY SYSTEM ......................................................................................25 
 
EDWARDS DILATOR KIT ................................................................................................25 
 
EDWARDS ESHEATH INTRODUCER .................................................................................25 
5 
STUDY OUTCOMES .........................................................................................................26 
6 
STUDY POPULATION ......................................................................................................26 
 
INCLUSION CRITERIA ....................................................................................................26 
 
EXCLUSION CRITERIA ...................................................................................................26 
7 
STUDY PROCEDURES .....................................................................................................28 
 
INFORMED CONSENT ....................................................................................................28 
 
SCREENING .................................................................................................................28 
 
Case Review .......................................................................................................................... 30 
 
PROCEDURE ................................................................................................................30 
 
Device Preparation ................................................................................................................ 31 
 
Antithrombotic Recommendations ......................................................................................... 31 
 
Antibiotic Prophylaxis ............................................................................................................. 32 
 
Contrast Media ....................................................................................................................... 32 
 
Radiation Precautions ............................................................................................................ 32 
 
POST-PROCEDURE .......................................................................................................32 
 
DISCHARGE .................................................................................................................32 
 
FOLLOW-UP .................................................................................................................33 
 
30 Days (+ 7 days) ................................................................................................................. 33 
 
1 Year (+ 30 days) ................................................................................................................. 34 
 
2 through 5, 7 and 10 years (+ 45 days) ................................................................................ 35 
 
6, 8 and 9 years (+ 45 days) .................................................................................................. 35 
 
IMAGING ASSESSMENTS ...............................................................................................35 
 
NEUROLOGICAL ASSESSMENTS .....................................................................................35 
 
QOL QUESTIONNAIRES .................................................................................................35 
 
SUBJECT DISCONTINUATION .........................................................................................36 
8 
ADVERSE EVENTS ..........................................................................................................39 

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ADVERSE EVENT DEFINITIONS ......................................................................................39 
 
INVESTIGATOR ASSESSMENT OF AES ............................................................................39 
 
AE REPORTING REQUIREMENTS ...................................................................................40 
 
Events that do not require reporting to the Sponsor .............................................................. 41 
 
SPONSOR ASSESSMENT OF AES ...................................................................................42 
 
DEVICE MALFUNCTIONS ................................................................................................42 
9 
RISKS AND BENEFIT ANALYSIS ....................................................................................43 
 
POTENTIAL BENEFITS ...................................................................................................43 
 
POTENTIAL RISKS .........................................................................................................43 
 
Risk Minimization ................................................................................................................... 45 
10 
STATISTICAL ANALYSIS .............................................................................................45 
 
ANALYSIS POPULATIONS ...............................................................................................45 
 
GENERAL STATISTICAL METHODOLOGY .........................................................................45 
11 
STUDY ADMINISTRATION ...........................................................................................46 
 
GENERAL STUDY ORGANIZATION ..................................................................................46 
 
STEERING COMMITTEE .................................................................................................46 
 
CASE REVIEW BOARD ...................................................................................................46 
 
DATA SAFETY MONITORING BOARD ...............................................................................46 
 
CLINICAL EVENTS COMMITTEE ......................................................................................47 
 
ECHOCARDIOGRAPHIC CORE LAB ..................................................................................47 
 
COMPUTED TOMOGRAPHY CORE LAB ............................................................................47 
 
IMAGE MANAGEMENT....................................................................................................47 
 
HISTOPATHOLOGY ........................................................................................................47 
 SITE PERSONNEL TRAINING ..........................................................................................47 
 DEVICE MANAGEMENT ..................................................................................................48 
 Investigational Device ............................................................................................................ 48 
 Device Storage ...................................................................................................................... 48 
 Device Accountability ............................................................................................................. 48 
 DATA MANAGEMENT .....................................................................................................48 
 MONITORING PROCEDURES ..........................................................................................48 
 AUDITING .....................................................................................................................49 
 PUBLICATION POLICY ....................................................................................................49 
12 
ETHICAL AND REGULATORY CONSIDERATIONS ....................................................49 
 
APPLICABLE REGULATIONS ...........................................................................................49 
 
INSTITUTIONAL REVIEW BOARD .....................................................................................49 
 
INFORMED CONSENT ....................................................................................................49 
 
CONFIDENTIALITY .........................................................................................................50 
 
INVESTIGATOR RECORDS ..............................................................................................50 
 
INVESTIGATOR REPORTS ..............................................................................................50 
 
AMENDING THE PROTOCOL ...........................................................................................51 
 
PROTOCOL DEVIATIONS ................................................................................................51 
APPENDIX A. 
ABBREVIATIONS ........................................................................................52 
APPENDIX B. 
DEFINITIONS ...............................................................................................55 
APPENDIX C. 
REFERENCES .............................................................................................70 
 

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LIST OF TABLES 
Table 1: CENTERA Study #2014-03: Demographics and Baseline Characteristics .................................. 13 
Table 2: CENTERA Study #2014-03: Primary Endpoint: 30-Day All-Cause Mortality (AT Population, 
N=203) ........................................................................................................................................................ 15 
Table 3: CENTERA Study #2014-03: Device Success at 30 Days (AT Population, N=203) ..................... 16 
Table 4: CENTERA Study #2014-03: CEC-Adjudicated AEs through 1 Year (KM) (AT Population, N=203)
 .................................................................................................................................................................... 16 
Table 5: CENTERA Study #2014-03: Patient Prosthesis Mismatch through 1 Year (VI Population*, 
N=197) ........................................................................................................................................................ 18 
Table 6: CENTERA Study #2014-03: Prosthetic Valve Dysfunction through 1 Year (VI Population*, 
N=197) ........................................................................................................................................................ 18 
Table 7: CENTERA Study #2014-03: Effectiveness Endpoints through 1 Year (VI Population*, N=197) .. 19 
Table 8: CENTERA THV Sizing Dimensions .............................................................................................. 25 
Table 9: Recommended Antithrombotic Regimen ...................................................................................... 31 
Table 10: Schedule of Assessments ........................................................................................................... 37 
 
 
 

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PROTOCOL SYNOPSIS 
Title 
A Prospective, Single-arm, Controlled, Multicenter Study to Establish the 
Safety and Effectiveness of the CENTERA THV System in IntermEDiate 
Risk Patients who have Symptomatic, Severe, Calcific, Aortic Stenosis 
Requiring Aortic Valve Replacement (ExCEED) 
Objective 
Following discontinuation of the CENTERA program, the objective is to 
monitor the safety and valve performance of the Edwards CENTERA 
Transcatheter Heart Valve (THV) System in patients with symptomatic, 
severe, calcific aortic stenosis who are at intermediate operative risk for 
surgical aortic valve replacement (SAVR) 
Study Device 
Edwards CENTERA THV System 
Control 
NA 
Study Design 
Prospective, single-arm, multicenter study. 
Study 
Population 
Subjects with symptomatic, severe, calcific AS and appropriate iliofemoral 
anatomy who are at intermediate operative risk 
Sample Size 
A sample size of 750 subjects was planned; 101 subjects were enrolled at 
the time of enrollment closure.  Up to two roll-in subjects were allowed per 
site; roll-in subjects were not counted towards the enrolled sample size. 
Study Sites 
Up to 65 actively enrolling sites in the US was planned; 23 US sites enrolled 
subjects at the time of enrollment closure. 
Visit Schedule 
Office Visit:  Screening, Procedure, Post-Procedure, Discharge, 30 days, 
Years 1-5, 7 and 10 
Phone:  Years 6, 8, 9 
Study 
Outcomes 
The following outcomes will be evaluated: 
1. Mortality at 30 days, 1 year and annually (up to 10 years) 
2. Stroke at 30 days, 1 year and annually (up to 10 years) 
3. Aortic valve reintervention at 30 days, 1 year and annually (up to 10 
years) 
4. Structural valve deterioration at years 1-5, 7 and 10 
5. Hemodynamic valve performance evaluation by echocardiography 
including AV stenosis and AV regurgitation (paravalvular & central) at 
30 days, and years 1-5, 7 and 10 
Inclusion 
Criteria 
Candidates must meet all of the following criteria to be included in the study: 
1. Severe, calcific AS meeting the following transthoracic echocardiogram 
(TTE) criteria: 
• 
AV area ≤ 1.0 cm2 OR AV area index ≤ 0.6 cm2/m2 
• 
Jet velocity ≥ 4.0 m/s OR mean gradient ≥ 40 mmHg 

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2. NYHA functional class ≥ II 
3. Judged by the Heart Team to be at intermediate risk for open surgical 
therapy (i.e., predicted risk of surgical mortality ≥ 3% and < 8% at 30 
days, based on the Society of Thoracic Surgeons (STS) risk score and 
other clinical co-morbidities unmeasured by the risk calculator) 
4. The subject has been informed of the nature of the study, agrees to its 
provisions and has provided written informed consent as approved by 
the Institutional Review Board/Ethics Committee of the respective 
clinical site. 
Exclusion 
Criteria 
Candidates will be excluded from the study if any of the following 
conditions are present: 
1. Native aortic annulus size unsuitable for sizes 23, 26 or 29 mm 
CENTERA THV based on 3D imaging analysis 
2. Aortic valve is unicuspid, bicuspid or non-calcified 
3. Pre-existing mechanical or bioprosthetic valve in any position.  (Of note, 
mitral ring is not an exclusion). 
4. Known hypersensitivity to Nitinol (nickel or titanium) 
5. Severe aortic regurgitation (> 3+) 
6. Severe mitral regurgitation (> 3+) or ≥ moderate stenosis 
7. Ventricular dysfunction with left ventricular ejection fraction (LVEF) < 
30% 
8. Cardiac imaging (echocardiography, computed tomography and/or 
magnetic resonance imaging) evidence of intracardiac mass, thrombus 
or vegetation 
9. Evidence of an acute myocardial infarction ≤ 30 days before the valve 
implant procedure 
10. Subjects with planned concomitant ablation for atrial fibrillation 
11. Hypertrophic cardiomyopathy with obstruction (HOCM) 
12. Coronary anatomy that increases the risk of coronary artery obstruction 
post-TAVR 
13. Complex coronary artery disease (CAD): 
a. Unprotected left main coronary artery 
b. SYNTAX score > 32 (in the absence of prior revascularization) 
c. Heart Team assessment that optimal revascularization cannot be 
performed 
14. Iliofemoral vessel characteristics that would preclude safe placement of 
the introducer sheath. 
15. Significant abdominal or thoracic aortic disease that would preclude 
safe passage of the delivery system 

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16. Active bacterial endocarditis within 180 days of the valve implant 
procedure 
17. Stroke or transient ischemic attack within 90 days of the valve implant 
procedure 
18. Symptomatic carotid or vertebral artery disease or successful treatment 
of carotid stenosis within 30 days of the valve implant procedure 
19. Severe lung disease (Forced Ejection Volume 1 (FEV1) < 50% 
predicted) or currently on home oxygen 
20. Severe pulmonary hypertension (e.g., pulmonary artery systolic 
pressure ≥ 2/3 systemic pressure) 
21. Hemodynamic or respiratory instability requiring inotropic support, 
mechanical ventilation or mechanical heart assistance within 30 days of 
the valve implant procedure 
22. History of cirrhosis or any active liver disease 
23. Renal insufficiency (estimated glomerular filtration rate (eGFR) < 30 
mL/min per the Cockcroft-Gault formula) and/or renal replacement 
therapy at the time of screening 
24. Leukopenia (WBC < 3000 cell/mL), anemia (Hgb < 9 g/dL), 
thrombocytopenia (Plt < 50,000 cell/mL), history of bleeding diathesis 
or coagulopathy or hypercoagulable states 
25. Inability to tolerate or condition precluding treatment with antithrombotic 
therapy during or after the valve implant procedure 
26. Absolute contraindications or allergy to iodinated contrast that cannot 
be adequately treated with pre-medication 
27. Significant frailty as determined by the Heart Team (after objective 
assessment of frailty parameters) 
28. Immobility that would prevent completion of study procedures (e.g., six-
minute walk tests, etc.) 
29. Subject refuses blood products 
30. Body mass index > 50 kg/m2 
31. Estimated life expectancy < 24 months 
32. Positive urine or serum pregnancy test in female subjects of 
childbearing potential 
33. 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.  Observational studies are not 
considered exclusionary. 
Statistical 
Methods 
Summary data for the 101 enrolled patients will be presented with descriptive 
statistics; no hypothesis testing will be performed. 

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Principal 
Investigators 
Martin Leon, MD, FACC 
Columbia University Medical Center/ NY Presbyterian Hospital 
New York, NY 
Sponsor 
Edwards Lifesciences LLC 
One Edwards Way 
Irvine, CA 92614 
 
 

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INVESTIGATOR SIGNATURE PAGE 
Protocol Title:  ExCEED: A Prospective, Single-arm, Controlled, Multicenter Study to Establish 
the Safety and Effectiveness of the CENTERA THV System in IntermEDiate Risk Patients who 
have Symptomatic, Severe, Calcific, Aortic Stenosis Requiring Aortic Valve Replacement  
 
I have read this protocol and agree to adhere to its requirements.  I will ensure that the study is 
conducted in compliance with the protocol, Good Clinical Practice, Declaration of Helsinki and all 
applicable regulatory requirements. 
 
 
 
_________________________________________________ 
Investigative Site Name 
 
 
 
_________________________________________________ 
Site Principal Investigator Name (print) 
 
 
 
 
______________________________ 
 
_____________ 
Site Principal Investigator Signature  
 
Date 
 
 

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1 INTRODUCTION 
 
Aortic Stenosis 
Aortic stenosis (AS) is one of the most common valvular diseases in developed countries, 
affecting ~5% of adults above the age of 65, and its prevalence is projected to increase over the 
next decade with an aging population.1,2  AS is a progressive, debilitating and life-threatening 
disease if left untreated.  The pathology involves progressive calcification of the leaflets that 
results in stenosis which limits valve opening.  The consequences of valve obstruction include 
increased afterload, left ventricular hypertrophy, and a decrease in systemic and coronary blood 
flow.  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 without intervention.  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.3 
Bicuspid aortic valve morphology is a common congenital valvular abnormality, occurring in 0.5% 
to 2% of the general population.4  AS is also a frequent complication in this population and may 
occur at a younger age in patients with a bicuspid valve, when compared with patients with a 
tricuspid aortic valve morphology.5,6 
 
Treatment of AS 
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.7,8  Treatment options for patients with severe, symptomatic AS include medical 
management, percutaneous balloon aortic valvuloplasty (BAV) or aortic valve replacement (AVR). 
AVR is considered the gold standard for treatment of patients with severe, symptomatic AS 9.  
AVR may be performed surgically or percutaneously.  Outcomes after surgical AVR (SAVR) are 
excellent in patients who do not have a high procedural risk, resulting in an improvement in 
symptoms, and in most patients, an improvement in exercise tolerance.10-14 
Transcatheter aortic valve replacement (TAVR) was originally developed as an alternative to 
SAVR in patients who were at high risk for surgical mortality or who were not suitable for surgical 
intervention, with the first successful TAVR procedure performed by Cribier and colleagues in 
2002.15 
The Placement of AoRtic TranNscathetER valve (PARTNER) study, Cohort B compared standard 
medical therapy (including BAV) to TAVR in patients with severe AS who were not candidates for 
surgical intervention.  Mortality rates at 1 year were significantly lower in the TAVR cohort 
compared to those who underwent medical therapy (30.7% vs. 50.7%, p<0.001).16  At 5-years, 
71.8% of TAVR patients had died compared to 93.6% of patients treated medically (p<0.0001).17 
In another study evaluating treatment of patients not suitable for surgery, self-expanding valves 
also showed superiority to medical therapy.  Comparing to an objective performance goal (OPG) 

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derived from the medical therapy arm of the PARTNER 1 Cohort B study, the rate of all-cause 
mortality or major stroke at 12 months was 26.0% with self-expanding TAVR versus 43.0% with 
the medical therapy OPG (p < 0.0001).18 
Two broad categories of devices for TAVR include balloon-expandable valves and self-expanding 
valves.  The Edwards SAPIEN transcatheter heart valve (THV), the first-generation balloon-
expandable valve, consists of a trileaflet, bovine pericardial tissue valve attached to a stainless-
steel frame; this valve has been commercially available in the US since November 2011.  Newer 
generations of balloon-expandable valves include the Edwards SAPIEN XT THV and the Edwards 
SAPIEN 3 THV, which have cobalt chromium frames. 
Self-expanding valves have the advantage of being able to be recaptured and repositioned prior 
to detachment.  The first self-expanding THV, the Medtronic CoreValve System (Medtronic Inc., 
Minneapolis, MN), obtained Food and Drug Administration (FDA) approval in January 2014.  The 
CoreValve consists of self-expanding trileaflet porcine pericardial tissue with a Nitinol frame.  This 
was followed by the Medtronic CoreValve Evolut R valve and later by the newest-generation 
Evolut Pro valve.  A number of other self-expanding THVs are available outside the US. 
Although patients with bicuspid valve morphology have historically been excluded from TAVR 
studies, recent reports indicate the use of transcatheter heart valves in these patients is feasible 
and effective with favorable valve performance.19-23 
 
TAVR vs. SAVR 
Numerous studies have been performed comparing TAVR to SAVR.  Studies comparing the two 
treatments in patients at high surgical risk have shown superiority of TAVR to SAVR with both 
balloon-expandable and self-expanding valves: 
• 
In the PARTNER study using the balloon-expandable SAPIEN THV, 1-year mortality rates 
were reported to be 24.2% vs. 26.8% (p = 0.001 for noninferiority) for TAVR and SAVR, 
respectively.  During 5-year follow-up, mortality rates were similar between the TAVR and 
SAVR (67.8% vs. 62.4%, p=0.76).  There was also no statistical difference between the 
two groups in the rate of stroke, repeat hospitalization or the need for a new pacemaker 
at one year, however peri-procedural risks at 30 days differed with statistically significant 
higher risk of major bleeding and new-onset atrial fibrillation with SAVR and higher 
incidence of vascular complications with TAVR.24 
• 
In a randomized study of patients using the self-expanding CoreValve, the rate of all 
cause-death at 1 year was significantly lower in the TAVR group than in the surgical group 
(14.2% vs. 19.1%), with an absolute reduction in risk of 4.9 percentage points (P<0.001 
for noninferiority; P = 0.04 for superiority).  The rate of major adverse cardiovascular and 
cerebrovascular events (MACCE) at 1 year was significantly lower in the TAVR group than 
in the SAVR group (20.4% vs. 27.3%, P = 0.03).  Major vascular complications and 
permanent pacemaker implantations were significantly more frequent in the TAVR group 
than in SAVR, whereas bleeding, acute kidney injury (AKI), and new-onset atrial fibrillation 
were significantly more common in the SAVR group than in the TAVR group.25 

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• 
Similar results were found in a large 4659 patients meta-analysis, which showed that 
TAVR had similar cardiovascular and all-cause mortality to SAVR at early and long-term 
follow-up.  There was no significant difference in the incidence of myocardial infarction 
(MI) (p = 0.59), stroke (p = 0.36), and transient ischemic attack (TIA) (p = 0.85) at averages 
of 72, 66, and 89 weeks, respectively.  TAVR was superior to SAVR for major bleeding 
complications and noninferior to SAVR for MACCE.26 
In patients with intermediate surgical risk, TAVR has been shown to be at least non-inferior to 
SAVR: 
• 
In trials evaluating balloon-expandable valves, there was no difference between TAVR 
and SAVR for the primary endpoint of all-cause death or disabling stroke at 2 years 
(Hazard Ratio: 0.89; 95% CI: 0.73 to 1.09; p=0.25).  All-cause mortality occurred in 16.7% 
of those randomized to TAVR with SAPIEN XT, compared with 18.0% of those treated 
with SAVR.  Disabling stroke occurred in 6.2% of patients treated with TAVR and 6.3% of 
patients treated with SAVR27  In a propensity score-matched comparison of the SAPIEN 
3 TAVR patients and PARTNER II Cohort A SAVR patients, TAVR was both noninferior 
and superior to SAVR (propensity score pooled weighted proportion difference: –9.2%; 
95% Confidence Interval (CI): –13.0 to –5.4; p<0.0001).  At 1 year, the rate of all-cause 
death was 7.4%, disabling stroke occurred in 2%, reintervention was required in 1%, and 
moderate or severe paravalvular leak (PVL) was seen in 2%28 
• 
A randomized study comparing TAVR with the self-expanding CoreValve to SAVR showed 
TAVR to be non-inferior alternative to SAVR.  At 24 months, the estimated incidence of 
the primary endpoint composite of all-cause death and disabling stroke was 12.6% in the 
TAVR group and 14.0% in the surgery group (95% credible interval [Bayesian analysis] 
for difference, −5.2 to 2.3%; posterior probability of noninferiority, >0.999).29 
 
As a result of these findings, the American College of Cardiology (ACC)/American Heart 
Association (AHA) guideline committees have provided TAVR with a Class I and IIa 
recommendation for patients with severe AS with high/prohibitive and intermediate surgical risk, 
respectively.30  And according to the 2017 European Society of Cardiology (ESC)/ European 
Association for Cardio-Thoracic Surgery (EACTS) guidelines on valvular heart diseases, TAVR 
is favored over SAVR in elderly patients with suitable transfemoral access and elevated surgical 
risk.31 
 
CENTERA THV Clinical History 
The following section presents the results of 3 clinical studies sponsored by Edwards 
Lifesciences.  These studies reported the incidence of mortality, adverse events and a summary 
of device efficacy including hemodynamic valve performance and functional improvement in 
implanted patients. 
The CENTERA THV System received CE Mark approval in February 2018.  Edwards 
discontinued the CENTERA program in July 2019; the CENTERA THV System is no longer 
commercially available. 

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CENTERA Study #2014-03 
The CENTERA THV clinical study (#2014-03) was a non-randomized, prospective, multi-center 
safety and device success study.  A total of 247 patients deemed at high risk for surgical 
intervention were enrolled in the CENTERA trial at 26 participating sites from March 12, 2015 
through June 28, 2016. 
Treatment was initiated in 203 patients (As Treated Population).  Primary and secondary 
endpoints were evaluated for the As Treated population.  A CENTERA THV (Model 9550C) was 
implanted in 198 patients (Valve Implant Population).  However, the CENTERA THV was 
explanted in one patient on the same day as the implant procedure due to coronary artery 
obstruction.  Hemodynamic and echocardiographic assessments were performed in 197 patients. 
Patients were assessed at the following intervals: baseline, hospital discharge, 30 days, 6 months 
and 1 year and will be followed annually thereafter through 5 years. 
 
Demographics and Baseline Characteristics 
Mean age at enrollment in the As Treated population (AT Population, N=203) was 82.7 ± 5.5 
years, and ranged from 60 to 94 years.  The majority of patients were female (67.5%).  Mean STS 
score was 6.1% ± 4.2% and there were 138/203 patients in New York Heart Association (NYHA) 
functional Class III/IV (68.0%).  Demographics and baseline characteristics are presented in 
Table 1. 
Table 1: CENTERA Study #2014-03: Demographics and Baseline Characteristics 
Baseline Characteristic 
Summary 
Statistic 
As Treated Population 
(N=203) 
Valve Implant Population 
(N=198) 
Age (Years) 
n 
203 
198 
Mean 
82.7 
82.8 
Std 
5.51 
5.42 
Median 
84.0 
84.0 
Min 
60.0 
60.0 
Max 
94.0 
94.0 
Sex 
Female 
n / N (%) 
137/203 (67.5%) 
136/198 (68.7%) 
Male 
n / N (%) 
66/203 (32.5%) 
62/198 (31.3%) 
Height (cm) 
n 
203 
198 
Mean 
163.6 
163.5 
Std 
8.75 
8.60 
Median 
163.0 
162.5 
Min 
145.0 
145.0 
Max 
188.0 
188.0 
Weight (kg) 
n 
203 
198 
Mean 
71.8 
71.7 

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Table 1: CENTERA Study #2014-03: Demographics and Baseline Characteristics 
Baseline Characteristic 
Summary 
Statistic 
As Treated Population 
(N=203) 
Valve Implant Population 
(N=198) 
Std 
16.52 
16.01 
Median 
71.0 
70.7 
Min 
40.0 
40.0 
Max 
153.2 
153.2 
Body Mass Index (kg/m2) 
n 
203 
198 
Mean 
26.8 
26.8 
Std 
5.36 
5.33 
Median 
26.0 
26.0 
Min 
14.3 
14.3 
Max 
44.8 
44.8 
Body Surface Area (m2) 
n 
203 
198 
Mean 
1.8 
1.8 
Std 
0.21 
0.21 
Median 
1.8 
1.8 
Min 
1.3 
1.3 
Max 
2.7 
2.7 
RISK SCORES 
STS Score 
n 
203 
198 
Mean 
6.1 
6.2 
Std 
4.19 
4.22 
Median 
5.0 
5.1 
Min 
1.4 
1.5 
Max 
28.0 
28.0 
Logistic EuroSCORE 1 
n 
203 
198 
Mean 
17.1 
17.1 
Std 
9.84 
9.92 
Median 
15.2 
15.2 
Min 
3.6 
3.6 
Max 
84.0 
84.0 
EuroSCORE 2 
n 
202 
198 
Mean 
5.1 
5.1 
Std 
3.95 
3.96 
Median 
3.8 
3.8 
Min 
0.8 
0.8 
Max 
27.2 
27.2 
NYHA Class 
Class I 
n / N (%) 
1/203 (0.5%) 
1/198 (0.5%) 

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Table 1: CENTERA Study #2014-03: Demographics and Baseline Characteristics 
Baseline Characteristic 
Summary 
Statistic 
As Treated Population 
(N=203) 
Valve Implant Population 
(N=198) 
Class II 
n / N (%) 
64/203 (31.5%) 
62/198 (31.3%) 
Class III 
n / N (%) 
126/203 (62.1%) 
124/198 (62.6%) 
Class IV 
n / N (%) 
12/203 (5.9%) 
11/198 (5.6%) 
NYHA Class Grouped 
Class I/II 
n / N (%) 
65/203 (32.0%) 
63/198 (31.8%) 
Class III/IV 
n / N (%) 
138/203 (68.0%) 
135/198 (68.2%) 
Source: Table 1.3 based on data extracted 18JAN2018 and run on 19JAN2018 
 
 
Procedural Information 
The CENTERA THV was implanted via transfemoral access in 198 of 203 patients (97.5%).  A 
size 26 mm valve was implanted in 117 patients (59.1%), a size 29 mm valve was implanted in 
59 patients (29.8%), and a size 23 mm valve was implanted in 22 patients (11.1%).  The 
CENTERA THV was recaptured and repositioned in 7 patients (3.4%) with no ventricular or aortic 
injury.  There were no ectopic valve deployments. 
 
Primary Endpoint: 30-Day All-Cause Mortality 
Two patients died within 30 days after the index procedure.  The Kaplan-Meier (KM) estimate for 
all-cause mortality at 30-days was 0.99%.  The primary endpoint was met as this rate is lower 
than the study hypothesis of <10% mortality at 30-days post-index procedure.  A summary of all-
cause mortality is presented in Table 2. 
Table 2: CENTERA Study #2014-03: Primary Endpoint: 30-Day All-Cause Mortality 
(AT Population, N=203) 
Event 
KM 
Rate* 
SE of 
KM 
90% CI 
No. of 
Events 
No. of Pts 
with Events 
No. of Pts 
at Risk 
P-
Value† 
All-Cause Mortality 
0.0099 0.0069 (0.0031, 0.0312) 
2 
2 
199 
<.0001 
Source: Table 2.1 based on data extracted 18JAN2018 and run on 19JAN2018 
Note: Imputed dates are used for events with missing or incomplete onset dates. 
* Kaplan-Meier estimates are through 30 days.  Events occurring after 30 days are not included in this analysis. 
† P-value is from one-sided test on a null hypothesis that the event rate was ≥10%. 
 
 
 

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Secondary Endpoint: Device Success at 30 Days 
Overall device success was reported in 131 of 138 patients (94.9%).  A summary of device 
success is presented in Table 3. 
Table 3: CENTERA Study #2014-03: Device Success at 30 Days 
(AT Population, N=203) 
Factor 
Result 
Overall Device Success* 
131/138 (94.9%) 
Factor 1: Alive at 3 Days (CEC) 
201/203 (99.0%) 
Factor 2: Single device in proper position 
160/165 (97.0%) 
Factor 3: Intended Performance of the CENTERA valve at 30 Days (echo core 
lab) 
159/161 (98.8%) 
Source: Table 3.1.1 based on data extracted 18JAN2018 and run on 19JAN2018 
Note: Summary statistics: Categorical measures – n/N (%) 
* Device success is defined as a composite of the following events: 
Factor 1: Absence of procedural mortality 
Factor 2: Correct positioning of a single prosthetic valve into the proper anatomical location 
Factor 3: Intended performance of the prosthetic heart valve (per the 30 day core lab echo assessment). 
The intended performance is defined as 
 • Total AR of none/trace/mild/mild-moderate and 
 • At least one of the following is true: 
   o Patient prosthesis mismatch of insignificant and mean gradient < 20 mmHg or 
   o Patient prosthesis mismatch of insignificant and peak velocity < 3 m/s or 
   o Mean Gradient < 20 mmHg and peak velocity < 3m/s 
 
 
CEC-Adjudicated Adverse Events 
Through 1 year of follow-up, there were a total of 18 deaths corresponding to a KM estimate of 
9.1% for all-cause mortality.  Nine deaths were adjudicated as cardiovascular-related deaths.  
Twenty-two cerebrovascular events were reported in 20 patients including 6 instances of TIA in 5 
patients and 16 stroke events in 15 patients, 8 of which were disabling stroke.  Through 1 year, 
new onset conduction abnormalities requiring pacemaker implantation was reported in 11 patients 
(KM estimate: 5.5%).  Clinical Events Committee (CEC)-adjudicated adverse events (AEs) are 
presented in Table 4. 
Table 4: CENTERA Study #2014-03: CEC-Adjudicated AEs through 1 Year (KM) 
(AT Population, N=203) 
Event 
30 Days 
180 Days 
1 Year* 
Death 
1.0% (2,2) 
5.0% (10,10) 
9.1% (18,18) 
Cardiovascular Death 
1.0% (2,2) 
2.0% (4,4) 
4.6% (9,9) 
Non-Cardiovascular Death 
0.0% (0,0) 
3.0% (6,6) 
4.7% (9,9) 
Myocardial Infarction 
1.5% (3,3) 
1.5% (3,3) 
2.0% (4,4) 
Periprocedural MI (Beginning ≤ 72 hours of Index 
procedure) 
1.0% (2,2) 
1.0% (2,2) 
1.0% (2,2) 
Spontaneous MI 
0.5% (1,1) 
0.5% (1,1) 
1.0% (2,2) 
Cerebrovascular Event 
5.0% (10,10) 
7.5% (15,15) 
10.2% (22,20) 
TIA 
1.0% (2,2) 
1.5% (3,3) 
2.6% (6,5) 

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Table 4: CENTERA Study #2014-03: CEC-Adjudicated AEs through 1 Year (KM) 
(AT Population, N=203) 
Event 
30 Days 
180 Days 
1 Year* 
Stroke (Any) 
4.0% (8,8) 
6.0% (12,12) 
7.6% (16,15) 
Disabling Stroke 
2.5% (5,5) 
3.0% (6,6) 
4.1% (8,8) 
Non-Disabling Stroke 
1.5% (3,3) 
3.0% (6,6) 
4.1% (8,8) 
Other Cerebrovascular Event 
0.0% (0,0) 
0.0% (0,0) 
0.0% (0,0) 
Bleeding‡ 
18.2% (40,37) 
NA 
NA 
Life-Threatening or Disabling Bleeding‡ 
4.9% (10,10) 
NA 
NA 
Major Bleeding‡ 
14.4% (30,29) 
NA 
NA 
Vascular Access Site and Access-related 
complications‡ 
6.4% (14,13) 
NA 
NA 
Major Vascular Complication‡ 
6.4% (14,13) 
NA 
NA 
Percutaneous closure device failure‡ 
0.5% (1,1) 
NA 
NA 
Acute Kidney Injury† 
3.5% (7,7) 
NA 
NA 
Stage I AKI† 
2.5% (5,5) 
NA 
NA 
Stage II AKI† 
0.5% (1,1) 
NA 
NA 
Stage III AKI† 
0.5% (1,1) 
NA 
NA 
New Conduction Abnormality 
24.7% (53,50) 28.3% (60,57) 29.4% (62,59) 
Atrial Fibrillation 
8.0% (16,16) 
11.0% (22,22) 11.6% (23,23) 
New Conduction Abnormality Requiring a Pacemaker 
4.9% (11,10) 
4.9% (11,10) 
5.5% (12,11) 
Prosthetic valve endocarditis 
0.0% (0,0) 
0.5% (1,1) 
0.5% (1,1) 
Prosthetic valve thrombosis 
0.0% (0,0) 
0.5% (1,1) 
1.0% (2,2) 
Valve embolization 
0.5% (1,1) 
0.5% (1,1) 
0.5% (1,1) 
Valve migration 
0.0% (0,0) 
0.0% (0,0) 
0.0% (0,0) 
Coronary artery obstruction requiring intervention‡ 
0.5% (1,1) 
NA 
NA 
Rehospitalization for valve related symptoms of CHF or 
worsening CHF 
0.5% (1,1) 
3.6% (8,7) 
6.8% (18,13) 
Source: Table 5.3.1.1 based on data extracted 18JAN2018 and run on 04FEB2018 
Note: Kaplan-Meier estimate - % (no. events, no. of subjects with the event) 
Imputed dates are used for events with incomplete onset dates 
* 1 Year is determined as 365 days. 
† Adjudicated only up to 7 days 
‡ Adjudicated only up to 30 days 
 
 
Patient Prosthesis Mismatch 
Patient prosthesis mismatch (PPM) was evaluated at discharge, 30 days, 6 months and 1 year.  
Among 129 patients evaluated at 1-year follow-up, moderate PPM was observed in 21 patients 
(16.3%) and severe PPM in 7 patients (5.4%).  A summary of PPM through 1 year is presented 
in Table 5. 

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Table 5: CENTERA Study #2014-03: Patient Prosthesis Mismatch through 1 Year 
(VI Population*, N=197) 
 
Insignificant 
Moderate 
Severe 
Discharge 
122/143 (85.3%) 
16/143 (11.2%) 
5/143 (3.5%) 
30 Days 
126/145 (86.9%) 
11/145 (7.6%) 
8/145 (5.5%) 
6 Months 
110/136 (80.9%) 
22/136 (16.2%) 
4/136 (2.9%) 
1 Year 
101/129 (78.3%) 
21/129 (16.3%) 
7/129 (5.4%) 
Source: Table 3.3.3.3 based on data extracted 18JAN2018 and run on 26JAN2018 
Note: Summary statistics: 
Categorical measures-No. / Total no. (%) 
Insignificant PPM is an EOAi > 0.85 cm2/m2 for patients with a BMI < 30 and EOAi > 0.70 cm2/m2 for patients with BMI ≥ 30 
Moderate PPM is an EOAi of 0.65-0.85 cm2/m2 for patients with a BMI < 30 and EOAi of 0.60-0.70 cm2/m2 for patients with BMI ≥ 30 
Severe PPM is an EOAi of <0.65 cm2/m2 for patients with a BMI < 30 and EOAi of <0.60 cm2/m2 for patients with BMI ≥ 30 
* Subject CNT 0354 014 was removed from VI population for this analysis due explant on the same day as implant procedure 
 
 
Structural Valve Deterioration Requiring Reintervention 
There have been no instances of structural valve deterioration (SVD) requiring reintervention 
reported for this study. 
 
Prosthetic Valve Dysfunction through 1 Year 
At 1-year follow-up, valve dysfunction was reported in 2 of 129 patients evaluated (1.6%).  A 
summary of prosthetic valve dysfunction is presented in Table 6. 
Table 6: CENTERA Study #2014-03: Prosthetic Valve Dysfunction through 1 Year 
(VI Population*, N=197) 
 
Discharge 
30 Days 
6 Months 
1 Year 
Prosthetic Valve Dysfunction 
2/160 (1.3%) 
3/151 (2.0%) 
3/142 (2.1%) 
2/129 (1.6%) 
95% Exact CI 
(0.15%, 4.44%) (0.41%, 5.70%) 
(0.44%, 6.05%) 
(0.19%, 5.49%) 
Source: Table 3.3.6.0 based on data extracted 18JAN2018 and run on 25JAN2018 
Note: Summary statistics: Categorical measures – n/N (%) 
* Subject CNT 0354 014 was removed from VI population for this analysis due explant on the same day as implant procedure 
A subject is considered to have prosthetic valve dysfunction if 
       • They have total aortic regurgitation or Moderate/Moderate-Severe/Severe or 
       • If the mean gradient ≥ 20 mmHg and EOA ≤ 1.1 for BSA ≥ 1.6; EOA ≤ 0.9 for BSA<1.6 or 
       • If the mean gradient ≥ 20 mmHg and DVI ≤ 0.35 or 
       • If EOA ≤ 1.1 for BSA ≥ 1.6; EOA ≤ 0.9 for BSA<1.6 and DVI  ≤ 0.35 
 
 
 

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Effectiveness Endpoints 
Hemodynamic and functional assessments demonstrated favorable clinical outcomes and valve 
performance in patients implanted with the CENTERA THV (Table 7).  Significant improvement 
from baseline in NYHA functional class and Six-Minute Walk Test (6MWT) evaluation was 
observed through 1 year of follow-up (p<0.0001 and p=0.0067, respectively).  Echocardiographic 
Core Lab evaluation demonstrated sustained significant reduction in mean transvalvular gradients 
from baseline through 1-year follow-up (p<0.0001).  Additionally, significant improvements in 
effective orifice area (EOA) and index orifice area from baseline through 1 year were reported 
(p<0.0001). 
Table 7: CENTERA Study #2014-03: Effectiveness Endpoints through 1 Year 
(VI Population*, N=197) 
 
Baseline 
Discharge 
30 Days 
6 Months 
1 Year 
NYHA Class 
I 
1 /197 
(0.5%) 
76 /187 
(40.6%) 
98 /185 
(53.0%) 
82 /176 
(46.6%) 
82 /171 
(48.0%) 
II 
62 /197 
(31.5%) 
90 /187 
(48.1%) 
74 /185 
(40.0%) 
77 /176 
(43.8%) 
74 /171 
(43.3%) 
III 
123 /197 
(62.4%) 
20 /187 
(10.7%) 
12 /185 
(6.5%) 
17 /176 
(9.7%) 
14 /171 
(8.2%) 
IV 
11 /197 
(5.6%) 
1 /187 
(0.5%) 
1 /185 (0.5%) 
0 /176 
(0.0%) 
1 /171 
(0.6%) 
P-value† 
NA 
<0.0001 
<0.0001 
<0.0001 
<0.0001 
Six Minute Walk 
Test (m) 
Summary at Visit 
230.5 ± 
123.54 (163) 
NA 
246.1 ± 
160.25 (151) 
NA 
NA 
Change from 
Baseline to Visit 
NA 
NA 
27.5 ± 115.02 
(133) 
NA 
NA 
P-Value‡ 
NA 
NA 
0.0067 
NA 
NA 
EQ5D 
Mobility 
Summary at Visit 
1.5 ± 0.51 
(193) 
1.5 ± 0.54 
(168) 
1.4 ± 0.54 
(161) 
NA 
1.5 ± 0.51 
(147) 
Change from 
Baseline to Visit 
NA 
-0.1 ± 0.56 
(166) 
-0.1 ± 0.57 
(159) 
NA 
-0.0 ± 0.63 
(146) 
P-Value‡ 
NA 
0.2174 
0.0138 
NA 
0.6011 
Self-Care 
Summary at Visit 
1.2 ± 0.45 
(193) 
1.3 ± 0.52 
(168) 
1.2 ± 0.47 
(161) 
NA 
1.3 ± 0.49 
(148) 
Change from 
Baseline to Visit 
NA 
0.1 ± 0.42 
(166) 
0.1 ± 0.49 
(159) 
NA 
0.1 ± 0.49 
(147) 
P-Value‡ 
NA 
0.0003 
0.1953 
NA 
0.0451 
Usual Activities Summary at Visit 
1.5 ± 0.61 
(193) 
1.6 ± 0.67 
(159) 
1.5 ± 0.63 
(160) 
NA 
1.5 ± 0.62 
(148) 
Change from 
Baseline to Visit 
NA 
0.1 ± 0.61 
(157) 
-0.0 ± 0.67 
(158) 
NA 
0.0 ± 0.68 
(147) 
P-Value‡ 
NA 
0.0505 
0.4750 
NA 
0.5431 

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Table 7: CENTERA Study #2014-03: Effectiveness Endpoints through 1 Year 
(VI Population*, N=197) 
 
Baseline 
Discharge 
30 Days 
6 Months 
1 Year 
Pain / 
Discomfort 
Summary at Visit 
1.6 ± 0.60 
(193) 
1.4 ± 0.55 
(166) 
1.5 ± 0.56 
(161) 
NA 
1.5 ± 0.61 
(147) 
Change from 
Baseline to Visit 
NA 
-0.2 ± 0.67 
(164) 
-0.1 ± 0.60 
(159) 
NA 
-0.1 ± 0.66 
(146) 
P-Value‡ 
NA 
0.0004 
0.0352 
NA 
0.3190 
Anxiety / 
Depression 
Summary at Visit 
1.3 ± 0.52 
(192) 
1.3 ± 0.49 
(167) 
1.3 ± 0.51 
(160) 
NA 
1.3 ± 0.56 
(147) 
Change from 
Baseline to Visit 
NA 
-0.1 ± 0.50 
(165) 
-0.1 ± 0.55 
(158) 
NA 
0.0 ± 0.57 
(145) 
P-Value‡ 
NA 
0.0858 
0.2495 
NA 
0.8846 
Overall State 
Summary at Visit 62.0 ± 16.35 
(192) 
66.6 ± 17.20 
(168) 
68.0 ± 16.96 
(161) 
NA 
67.3 ± 17.94 
(146) 
Change from 
Baseline to Visit 
NA 
5.1 ± 17.79 
(166) 
6.0 ± 17.11 
(158) 
NA 
5.5 ± 20.54 
(145) 
P-Value‡ 
NA 
0.0003 
<0.0001 
NA 
0.0015 
Echocardiographic measures 
Paravalvular 
Regurgitation 
None 
NA 
80 /169 
(47.3%) 
82 /160 
(51.3%) 
86 /151 
(57.0%) 
86 /137 
(62.8%) 
Trace 
NA 
15 /169 
(8.9%) 
17 /160 
(10.6%) 
14 /151 
(9.3%) 
13 /137 
(9.5%) 
Mild 
NA 
68 /169 
(40.2%) 
56 /160 
(35.0%) 
50 /151 
(33.1%) 
37 /137 
(27.0%) 
Mild-Moderate 
NA 
5 /169 
(3.0%) 
4 /160 (2.5%) 
1 /151 
(0.7%) 
1 /137 
(0.7%) 
Moderate 
NA 
1 /169 
(0.6%) 
1 /160 (0.6%) 
0 /151 
(0.0%) 
0 /137 
(0.0%) 
Moderate-Severe 
NA 
0 /169 
(0.0%) 
0 /160 (0.0%) 
0 /151 
(0.0%) 
0 /137 
(0.0%) 
Severe 
NA 
0 /169 
(0.0%) 
0 /160 (0.0%) 
0 /151 
(0.0%) 
0 /137 
(0.0%) 

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Table 7: CENTERA Study #2014-03: Effectiveness Endpoints through 1 Year 
(VI Population*, N=197) 
 
Baseline 
Discharge 
30 Days 
6 Months 
1 Year 
Total Aortic 
Regurgitation 
None 
37 /168 
(22.0%) 
72 /183 
(39.3%) 
71 /165 
(43.0%) 
77 /156 
(49.4%) 
83 /147 
(56.5%) 
Trace 
23 /168 
(13.7%) 
33 /183 
(18.0%) 
31 /165 
(18.8%) 
24 /156 
(15.4%) 
22 /147 
(15.0%) 
Mild 
92 /168 
(54.8%) 
71 /183 
(38.8%) 
58 /165 
(35.2%) 
54 /156 
(34.6%) 
40 /147 
(27.2%) 
Mild-Moderate 
12 /168 
(7.1%) 
6 /183 
(3.3%) 
4 /165 (2.4%) 
1 /156 
(0.6%) 
2 /147 
(1.4%) 
Moderate 
4 /168 
(2.4%) 
1 /183 
(0.5%) 
1 /165 (0.6%) 
0 /156 
(0.0%) 
0 /147 
(0.0%) 
Moderate-Severe 
0 /168 
(0.0%) 
0 /183 
(0.0%) 
0 /165 (0.0%) 
0 /156 
(0.0%) 
0 /147 
(0.0%) 
Severe 
0 /168 
(0.0%) 
0 /183 
(0.0%) 
0 /165 (0.0%) 
0 /156 
(0.0%) 
0 /147 
(0.0%) 
Effective Orifice 
Area (cm2) 
Summary at Visit 
0.7 ± 0.20 
(146) 
1.9 ± 0.48 
(143) 
1.9 ± 0.43 
(145) 
1.8 ± 0.42 
(136) 
1.7 ± 0.42 
(129) 
Change from 
Baseline to Visit 
NA 
1.2 ± 0.43 
(116) 
1.2 ± 0.40 
(113) 
1.1 ± 0.41 
(110) 
1.0 ± 0.40 
(100) 
P-Value‡ 
NA 
<0.0001 
<0.0001 
<0.0001 
<0.0001 
Indexed 
Effective Orifice 
Area (cm2/m2) 
Summary at Visit 
0.4 ± 0.12 
(146) 
1.1 ± 0.29 
(143) 
1.1 ± 0.28 
(145) 
1.1 ± 0.27 
(136) 
1.0 ± 0.27 
(129) 
Change from 
Baseline to Visit 
NA 
0.7 ± 0.26 
(116) 
0.7 ± 0.26 
(113) 
0.7 ± 0.26 
(110) 
0.6 ± 0.25 
(100) 
P-Value‡ 
NA 
<0.0001 
<0.0001 
<0.0001 
<0.0001 
Mean Aortic 
Valve Gradient 
(mmHg) 
Summary at Visit 40.6 ± 13.32 
(185) 
8.2 ± 3.23 
(186) 
7.2 ± 2.81 
(166) 
7.5 ± 2.95 
(161) 
8.1 ± 4.72 
(147) 
Change from 
Baseline to Visit 
NA 
-32.5 ± 
12.91 (178) 
-34.2 ± 13.36 
(159) 
-33.7 ± 
13.79 (152) 
-32.7 ± 
14.07 (139) 
P-Value‡ 
NA 
<0.0001 
<0.0001 
<0.0001 
<0.0001 
Source: Table 3.4 based on data extracted 18JAN2018 and run on 25JAN2018 
Note: Summary statistics: Categorical measures – n/N (%)    Continuous measures - mean ± SD (n) 
* Subject CNT 0354 014 was removed from VI population for this analysis due explant on the same day as implant procedure 
† P-value compares the NYHA at follow-up to baseline using a Fisher’s Exact Test. 
‡ The p-value is from a two-sided paired t-test with the null hypothesis that there is no change from baseline. 
 
 
 

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CENTERA Study #2012-03 
CENTERA study #2012-03 is a non-randomized, prospective, multicenter trial to assess the 
safety and device success of the Edwards CENTERA THV System (Model 9500G) in high surgical 
risk patients (STS Score ≥ 8) with symptomatic, severe AS who are indicated for AVR. 
 
Study Results 
From February 18, 2013 through August 23, 2013 there were 34 high surgical risk patients 
enrolled.  A database extract of September 6, 2016 was used for this report.  Mean age was 82.7 
± 4.6 years with a Logistic EuroSCORE of 22.7 ± 13.0 and STS Score of 7.1 ± 3.5.  The CENTERA 
THV was implanted in 32 out of 34 patients (94.1%).  With regard to the other two patients, one 
patient was converted to SAVR after the left ventricle was perforated by a guidewire; the 
procedure was initiated for the other patient but valve implantation was not attempted due to 
decline in the patient condition prior to introduction of the study device.  The two patients who did 
not receive the study implant died, resulting in a 30-day all-cause mortality rate of 5.9% in the AT 
population.  Of the 32 patients in whom the valve was implanted (VI population), there were no 
deaths at 30 days.  These rates are consistent with the study hypothesis of <10% mortality at 30-
days post-index procedure. 
Of the 32 enrolled patients in the VI population, 30 patients received a 26mm CENTERA THV 
(93.8%), and the remainder received the 23mm valve (6.3%).  The procedure was performed 
under conscious sedation for 21/32 patients (65.6%).  Predilation BAV was performed in all 
patients as specified per protocol and post-dilation was performed in 15/32 patients (46.9%).  The 
final valve deployment position was correct at the intended site in 31/32 patients (96.9%).  In one 
patient, the final position of the valve was more ventricular than intended, but the valve did not 
migrate or embolize.  No valve-in-valve procedures were performed. 
Follow-up evaluations are performed at discharge, 30 days, 6 months, and annually through 5 
years.  Three-year follow-up results are provided below. 
• 
KM estimate for all-cause mortality at 3 years was 29.9% (AT Population) 
o A total of 10 patients died; 5 deaths were due to cardiovascular causes and 5 deaths 
were considered non-cardiovascular related. 
• 
At 3 years, the incidence of CEC-adjudicated events was: 
o 2.9% for MI (n=1/34) 
o 5.9% for all stroke (n=2/34) 
o 14.7% for life-threatening or disabling bleeding (n=5/34) 
o 8.8% for vascular access related complications (n=3/34) 
o 11.8% for AKI (n=4/34) 
o 2.9% for SVD requiring repeat procedure (n=1/34) 
 
The CEC determined that there were no events of arrhythmia, prosthetic valve endocarditis, 
prosthetic valve thrombosis, valve embolization, valve migration and coronary artery obstruction 

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requiring intervention through 3 years. 
At every visit, the vast majority of patients with available NYHA data showed improvement from 
baseline.  Through 3 years of follow-up, there was an improvement in NYHA Class in 15 of 21 
patients evaluated while the remaining 6 remained in the same NYHA Class from baseline.  There 
were no patients with worsened NYHA functional status through 3 years. 
Echocardiographic endpoints were analyzed by a core laboratory.  At all visits, PVL was ≤ mild in 
most patients.  Moderate PVL was reported for 2 patients (9.1%) at discharge, and 1 patient 
(4.3%) at 30 days; no patients had severe PVL at any post-procedure time point.  Through 3 years 
of follow-up, there were no cases of > mild PVL among 12 patients evaluated.  The low incidence 
of PVL in the analyzed set of patients demonstrates the performance of the Edwards CENTERA 
THV. 
The mean aortic valve (AV) gradient decreased from 33.4 ± 8.5 mmHg from baseline to 7.3 ± 1.9 
mmHg at discharge, 7.0 ± 2.8 mmHg at 30 days, 7.5 ± 2.5 mmHg at 1 year, 8.7 ± 5.1 mmHg at 2 
years, and 7.5 ± 2.7 mmHg at 3 years.  The reduction in mean gradient from baseline at each 
visit was statistically significant. 
 
CENTERA Study #2010-08 
The purpose of this early feasibility study was to evaluate the safety and initial performance of the 
Edwards Self-Expanding THV with transarterial delivery system and accessories in symptomatic 
patients with severe calcific AS requiring AVR who were at high risk for open chest surgery due 
to existing co-morbidities. 
 
Study Results 
A total of 19 patients were enrolled in two phases between November 2010 and October 2012 at 
Asklepios Klinik in Hamburg, Germany.  In phase 1, under protocol version 001, 5 patients were 
enrolled in November and December 2010 and received valve model 9500TFX size 26 mm.  In 
phase 2, under protocol version 002, an additional 14 patients were enrolled between June 2012 
and October 2012 and received valve model 9500G sizes 23 mm (n=1) and 26 mm (n=13). 
The CENTERA THV model 9500TFX and delivery systems were obsoleted and replaced with the 
newer CENTERA THV model 9500G which incorporated changes in frame design and pericardial 
tissue leaflet treatment.  Clinical outcomes in patients implanted with CENTERA THV model 
9500TFX in Phase 1 (n=5) are not comparable to those obtained with the newer CENTERA THV 
model 9500G in Phase 2 (n=14).  Statistical analysis of safety and effectiveness were conducted 
for the 14 patients implanted with the CENTERA THV model 9500G. 
The primary safety endpoint for this study was freedom from death at 30 days after the implant 
procedure. 
• 
There were no patient deaths at 30 days among the initial 5 patients. 
• 
In the subsequent cohort of 14 patients there was 1 patient death at 30 days for a KM 
estimate for all-cause mortality at 30 days of 7.1%.  This rate is consistent with the study 

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hypothesis of <10% mortality at 30-days post-index procedure. 
• 
At 4 years, the incidence of all site-reported adverse events for the 14-patient cohort was: 
o 7.1% for bleeding 
o 7.1% for all stroke 
o 21.4% for heart failure 
o 7.1% for renal failure 
There were no unanticipated adverse events reported. 
Through 1 year of follow-up, 8 of 10 patients showed improvement over baseline in NYHA 
functional class while 2 patients remained the same.  There were no patients with worsened 
NYHA Class.  In 8 patients evaluated at 3 years, improvement in NYHA Class was observed in 7 
and 1 patient remained the same. 
At discharge, 13 of 14 patients had mild or less PVL and 1 patient had moderate PVL.  By 1 year 
follow-up, 8 of 9 patients had none/trace PVL and 1 patient presented with moderate PVL. 
The mean AV gradient decreased from 43.4 ± 12.64 mmHg at baseline to 10.6 ± 3.37 mmHg at 
discharge, 10.4 ± 2.67 mmHg at 30 days, 9.6 ± 4.75 mmHg at 6 months, 10.8 ± 3.38 mmHg at 1 
year, 13.3 ± 3.74 mmHg at 2 years, 16.3 ± 7.77 mmHg at 3 years and 12.0 mmHg at 4 years.  
The reduction in mean gradient from baseline at each visit to 2 years was statistically significant 
(p < 0.001 through 1 year and p = 0.0117 at 2 years). 
2 STUDY OBJECTIVE 
Following discontinuation of the CENTERA program, the objective of this study is to monitor the 
safety and valve performance of the Edwards CENTERA THV System in patients with 
symptomatic, severe, calcific AS who are at intermediate operative risk for SAVR. 
3 STUDY DESIGN 
This is a prospective, single-arm, multicenter study.  Enrollment of 750 subjects with symptomatic, 
severe, calcific AS was planned at up to 65 US sites; enrollment has been closed with 101 
subjects enrolled at 23 sites.  Up to two roll-in subjects were allowed per site; roll-in subjects were 
not counted towards the enrolled sample size. 
4 STUDY DEVICES 
The CENTERA THV System, model 9551S, consists of a THV that is pre-attached to the delivery 
system and protected within a loading capsule.  The THV and delivery system are supplied 
together in one package. 
The CENTERA THV System and accessories will be used per the Instructions for Use (IFU) and 
after sufficient training has been provided by Edwards. 

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CENTERA THV 
The CENTERA THV is composed of a self-expanding, radiopaque, Nitinol frame with trileaflet 
bovine pericardial tissue, and polyethylene terephthalate (PET) fabric.  The tissue leaflets are 
treated with a proprietary process that allows the valve to be stored dry. 
The CENTERA THV, available in 23, 26 and 29 mm sizes, is intended to be implanted in a native 
annulus size range comparable to the CT measurements shown in Table 8 below. 
Table 8: CENTERA THV Sizing Dimensions 
CENTERA THV Size 
23 mm 
26 mm 
29 mm 
Native Annulus Perimeter-Derived Diameter 
18-21 mm 
21-24 mm 
24-27 mm 
Native Annulus Perimeter 
56.5-66.0 mm 
66.0-75.4 mm 
75.4-84.8 mm 
Native Annulus Area 
254-346 mm² 
346-452 mm² 
452-573 mm² 
Minimum Access Vessel Diameter 
5.5 mm 
5.5 mm 
5.5 mm 
 
 
CENTERA Delivery System 
The delivery system is designed to be used to deliver the THV to the implant site via the 
transfemoral artery.  The system has a tapered distal tip which facilitates valve crossing, as well 
as a flex section which facilitates system tracking and positioning. 
The recommended minimum femoral-iliac vessel diameters for introduction of the CENTERA THV 
system are shown in .  Recommended vessel sizing is for use only with the 14F expandable 
sheath provided by Edwards. 
The delivery system has an integrated battery powered (6V total) motorized handle designed to 
advance or retract the delivery capsule for loading or deploying of the THV, respectively. 
NOTE:  The handle is protected against fluids (drip-proof equipment IPX1).  The handle is not 
suitable for use in the presence of a flammable anesthetic mixture.  The handle operates in a 
continuous mode and is internally battery powered.  The system constitutes a Type CF Applied 
Part. 
 
Edwards Dilator Kit 
The Edwards dilator kit contains a set of hydrophilically coated tapered dilators.  The 22F dilator 
is used to pre-dilate the expandable portion of the Edwards expandable sheath. 
 
Edwards eSheath Introducer 
Edwards 14F eSheath Introducer is used to introduce the CENTERA delivery system into the 
vasculature. 

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5 STUDY OUTCOMES 
The following outcomes will be evaluated: 
1. Mortality at 30 days, 1 year and annually (up to 10 years) 
2. Stroke at 30 days, 1 year and annually (up to 10 years) 
3. Aortic valve reintervention at 30 days, 1 year and annually (up to 10 years) 
4. SVD at years 1-5, 7 and 10 
5. Hemodynamic valve performance evaluation by echocardiography including AV stenosis 
and AV regurgitation (paravalvular & central) at 30 days, and years 1-5, 7 and 10. 
 
6 STUDY POPULATION 
The study population will be comprised of subjects with symptomatic, severe, calcific AS and 
appropriate iliofemoral anatomy who are at intermediate operative risk. 
 
Inclusion Criteria 
Candidates must meet all of the following criteria to be included in the study: 
1. Severe, calcific AS meeting the following transthoracic echocardiogram (TTE) criteria: 
• 
Aortic Valve Area (AVA) ≤ 1.0 cm2 OR AVA index ≤ 0.6 cm2/m2 
• 
Jet velocity ≥ 4.0 m/s OR mean gradient ≥ 40 mmHg 
2. NYHA functional class ≥ II 
3. Judged by the Heart Team to be at intermediate risk for open surgical therapy (i.e., 
predicted risk of surgical mortality ≥ 3% and < 8% at 30 days, based on the STS risk score 
and other clinical co-morbidities unmeasured by the risk calculator) 
4. The subject has been informed of the nature of the study, agrees to its provisions and has 
provided written informed consent as approved by the Institutional Review Board (IRB)/ 
Ethics Committee (EC) of the respective clinical site. 
 
 
Exclusion Criteria 
Candidates will be excluded from the study if any of the following conditions are present: 
1. Native aortic annulus size unsuitable for sizes 23, 26 or 29 mm CENTERA THV based on 
3D imaging analysis 
2. Aortic valve is unicuspid, bicuspid or non-calcified 
3. Pre-existing mechanical or bioprosthetic valve in any position.  (Of note, mitral ring is not an 
exclusion). 
4. Known hypersensitivity to Nitinol (nickel or titanium) 
5. Severe aortic regurgitation (> 3+) 

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6. Severe mitral regurgitation (> 3+) or ≥ moderate stenosis 
7. Ventricular dysfunction with left ventricular ejection fraction (LVEF) < 30% 
8. Cardiac imaging (echocardiography, computed tomography (CT) and/or magnetic 
resonance imaging (MRI)) evidence of intracardiac mass, thrombus or vegetation 
9. Evidence of an acute MI ≤ 30 days before the valve implant procedure 
10. Subjects with planned concomitant ablation for atrial fibrillation 
11. Hypertrophic cardiomyopathy with obstruction (HOCM) 
12. Coronary anatomy that increases the risk of coronary artery obstruction post-TAVR 
13. Complex coronary artery disease (CAD): 
a. Unprotected left main coronary artery 
b. SYNTAX score > 32 (in the absence of prior revascularization) 
c. Heart Team assessment that optimal revascularization cannot be performed 
14. Iliofemoral vessel characteristics that would preclude safe placement of the introducer 
sheath. 
15. Significant abdominal or thoracic aortic disease that would preclude safe passage of the 
delivery system 
16. Active bacterial endocarditis within 180 days of the valve implant procedure 
17. Stroke or TIA within 90 days of the valve implant procedure 
18. Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis 
within 30 days of the valve implant procedure 
19. Severe lung disease (Forced Ejection Volume 1 (FEV1) < 50% predicted) or currently on 
home oxygen 
20. Severe pulmonary hypertension (e.g., pulmonary artery systolic pressure ≥ 2/3 systemic 
pressure) 
21. Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or 
mechanical heart assistance within 30 days of the valve implant procedure 
22. History of cirrhosis or any active liver disease 
23. Renal insufficiency (estimated glomerular filtration rate (eGFR) < 30 mL/min per the 
Cockcroft-Gault formula) and/or renal replacement therapy at the time of screening 
24. Leukopenia (WBC < 3000 cell/mL), anemia (Hgb < 9 g/dL), thrombocytopenia (Plt < 50,000 
cell/mL), history of bleeding diathesis or coagulopathy or hypercoagulable states 
25. Inability to tolerate or condition precluding treatment with antithrombotic therapy during or 
after the valve implant procedure 
26. Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated 
with pre-medication 
27. Significant frailty as determined by the Heart Team (after objective assessment of frailty 
parameters) 
28. Immobility that would prevent completion of study procedures (e.g., six-minute walk tests, 
etc.) 

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29. Subject refuses blood products 
30. Body mass index (BMI) > 50 kg/m2 
31. Estimated life expectancy < 24 months 
32. Positive urine or serum pregnancy test in female subjects of childbearing potential 
33. 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.  Observational studies are 
not considered exclusionary. 
 
7 STUDY PROCEDURES 
 
Informed Consent 
The study investigator(s) and support staff will approach subjects with symptomatic, severe 
calcific AS who meet general requirements to assess their interest in participating in the study by 
providing them an overview of the study including the background, risks, benefits and study 
procedures.  If subjects are interested in participating in the study, the subject will sign the IRB/EC-
approved informed consent form (ICF) prior to any study-specific procedures being performed.  
All subjects consented should be entered into the study’s Electronic Data Capture (EDC) system. 
 
Screening 
The screening assessments will be completed within 30 days prior to the valve implant procedure, 
unless otherwise noted.  Screening assessments will include the following: 
Systems: 
• 
Medical History 
• 
Physical Assessment (height, weight, blood pressure and heart rate only) 
• 
Medications:  Antithrombotics (anticoagulants, antiplatelets, thrombolytics) only 
Risk: 
• 
STS Risk Score 
• 
EuroSCORE II 
• 
TAVR Risk Score 
Cardiopulmonary: 
• 
NYHA Functional Class 
• 
Canadian Cardiovascular Society (CCS) status of angina 
• 
12-lead Electrocardiogram (ECG) 
• 
TTE – Qualifying TTE must be performed within 90 days prior to the valve implant 
procedure. 
• 
3D Cardiac Imaging (CT, Transesophageal Echocardiogram (TEE) or cardiac MRI) with 
3D reconstruction to determine AV annulus area.  Qualifying cardiac imaging must be 

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performed within 1 year prior to the valve implant procedure. 
• 
Iliofemoral CT Angiography, including thoracic and abdominal scan with visualization of 
iliac and femoral arteries.  Iliofemoral CT Angiography must be performed within 1 year 
prior to the valve implant procedure. 
• 
Left Heart Catheterization to assess the severity of AS and, if applicable, the severity of 
CAD.  Qualifying catheterization must be performed within 1 year prior to the valve 
implant procedure. 
• 
Pulmonary Function Test – only for subjects with a history of lung disease 
• 
SYNTAX Score – only for subjects with significant native CAD 
Neurological: 
• 
National Institutes of Health Stroke Scale (NIHSS) 
• 
Modified Rankin Scale (mRS) 
• 
Mini Mental State Examination (MMSE) 
Clinical Laboratory Tests: 
• 
WBC, Hemoglobin, Platelet count 
• 
Prothrombin Time (PT) or International Normalized Ratio (INR) 
• 
Creatine Kinase (CK)/Creatine Kinase MB Isoenzyme (CKMB) and/or Troponins ≤ 72 
hours before the valve implant procedure 
• 
eGFR per the Cockcroft-Gault formula 
• 
Creatinine 
• 
Albumin (as part of Frailty Index), total bilirubin 
• 
Aspartame Aminotransferase (AST), Alanine Aminotransferase (ALT) – only for subjects 
with chronic liver disease 
• 
Pregnancy test (urine or serum) – only for female subjects of childbearing age 
Functional: 
• 
Frailty Index (5 Meter Walk Test, grip strength, Activities of Daily Living and serum 
Albumin) 
• 
6MWT 
• 
QoL Questionnaires 
o KCCQ 
o EQ-5D-5L 
o SF-36 
Candidates that have signed the ICF and do not meet the inclusion/exclusion criteria in Section 
6 will be considered a Screen Failure.  All assessments performed and the eligibility criteria that 
were not met will be entered into the EDC. 
Candidates that withdraw consent or expire prior to or after the Case Review but before the valve 

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implant procedure will also be considered a Screen Failure. 
 
Case Review 
Before a case is submitted for review, the site Principal Investigator and Heart Team will screen 
the subject for fundamental enrollment criteria.  It is required that at least one site surgeon 
Investigator personally examine the subject to determine operative risk.  Once fully screened and 
deemed an appropriate candidate, the site will submit the case for review and approval 
consideration by the Case Review Board. 
• 
If the case is approved by the Case Review Board, the subject may be scheduled for the 
valve implant procedure. 
• 
If the case is not approved, the subject’s status will be considered a Screen Failure. 
 
Edwards will maintain a record of the case presentation and case approval notes. 
 
Procedure 
The study devices will be used per the most current IFU for device sizing, preparation and 
recommended implant procedure.  Only physicians appropriately trained to the use of the device 
and identified on the Delegation of Authority (DoA) log on file with Edwards may perform the 
implant procedure in study subjects. 
The valve implant procedure will be considered to have started when the first interventional 
access-related puncture (arterial) is established.  Performance of TEE does not by itself constitute 
start of procedure. 
A subject will be considered enrolled in the study once the subject has signed the ICF and the 
valve implant procedure has begun, as defined above. 
It is strongly encouraged that the procedure be performed within 14 days of case review approval. 
Procedure assessments will include the following: 
Systems: 
• 
Medications:  Antithrombotics only 
• 
Adverse Events 
Cardiopulmonary: 
• 
Assessment of PVL and valve placement by either: 
o TEE, or 
o TTE and Aortogram 
Study 
subjects 
will 
be 
continuously 
monitored 
clinically, 
hemodynamically, 
and 
electrocardiographically during the procedure for all local, systemic side effects and 
complications. 

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If the procedure is aborted (prior to or after the start of the valve implant procedure), the procedure 
may be re-scheduled if the subject continues to meet all eligibility criteria. 
 
Device Preparation 
A detailed description of device preparation and required equipment is supplied in the IFU. 
 
Antithrombotic Recommendations 
Table 9 outlines the recommended antithrombotic regimen. 
Table 9: Recommended Antithrombotic Regimen 
Pre-Valve 
Implant 
Procedure 
• Aspirin (ASA) 81-100 mg QD 
• Subjects with a bare metal stent (BMS) within one month or drug-eluting stent 
(DES) within 12 months should be continued on Clopidogrel/prasugrel prior to 
their implant procedure. 
• Subjects in atrial fibrillation on warfarin should be bridged with low molecular 
weight (LMW) or unfractionated (UF) heparin prior to the implant procedure. 
• Subjects with persistent or paroxysmal atrial fibrillation and not on anticoagulation 
will not be required to have a TEE to rule out left atrial (LA) thrombus prior to 
implant procedure.  If intra-procedural TEE during TAVR reveals thrombus, 
implant procedure will be aborted and delayed until subject has been on warfarin 
or dabigatran for 30 days.  Note: thrombus must be eliminated in order to proceed 
with TAVR. 
• In subjects undergoing concomitant TAVR/Percutaneous Coronary Intervention 
(PCI), Clopidogrel loading with either 300 mg or 600 mg prior to the implant 
procedure is recommended in addition to ASA. 
Intraprocedural 
• Heparin will be given to achieve/ maintain activated clotting time (ACT) ≥ 250 sec. 
Post-Valve 
Implant 
Procedure 
Category I for Stroke Risk:  No atrial fibrillation, no recent stents 
• ASA 81 mg QD 
• Clopidogrel 300 mg load within 6 hours of the implant procedure (either pre or 
post) 
• Clopidogrel 75 mg QD for at least one month post-implant procedure 
Category II for Stroke Risk:  No atrial fibrillation, recent stents 
• ASA 81 mg QD 
• Clopidogrel 75 mg QD should be continued after the implant procedure without 
interruption for at least one month post-BMS and 12 months post-DES 
Category III for Stroke Risk:  Atrial fibrillation, no recent stents 
• ASA 81 mg QD 
• Subjects should be started on warfarin or dabigatran 24 hours post-TAVR if 
clinically safe and this should be continued for at least one month or indefinitely, if 
possible.  If clinically safe, subjects started on warfarin should be bridged with UF 
or LMW heparin until INR therapeutic. 
• If subjects are not a candidate for warfarin or dagibatran, Clopidogrel 75 mg QD 
can be considered as an alternative. 
Category IV for Stroke Risk:  Atrial fibrillation, recent stents 
• ASA 81 mg QD 
• Clopidogrel 75 mg QD for at least one month post-BMS or 12 months post-DES 
• Subjects should be started on warfarin or dabigatran 24 hours post-TAVR if 
clinically safe and continued indefinitely.  If clinically safe, subject’s being started 
on warfarin should be bridged with UF or LMW heparin until INR therapeutic. 

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Note: Any changes to antithrombotic regimen from study visit to study visit will be noted on the electronic Case Report 
Form (eCRF) including reason for change. 
 
 
Antibiotic Prophylaxis 
Study subjects should be prophylactically treated for endocarditis per the recommendations of 
the AHA 32. 
 
Contrast Media 
Careful management of contrast media is required.  Accurate measurement of the contrast used 
will be captured in the subject medical records. 
 
Radiation Precautions 
Radiation precautions will be adhered to per institutional standards.  If a radiation-induced skin 
injury is suspected, the Investigator must report an adverse event, and assess and treat the 
subject as medically necessary. 
 
Post-procedure 
The post-procedure time period is defined as the 48 hours after the subject exits the procedure 
room.  Subsequent monitoring will continue according to institutional standard of care. 
The following will be assessed during the post-procedure time period: 
Systems: 
• 
Medications:  Antithrombotics only 
• 
Adverse Events 
Cardiopulmonary: 
• 
12-lead ECG 
Neurological: 
• 
NIHSS 
All subjects should be assessed post-procedure to determine if there is evidence of neurological 
impairment.  If symptoms of stroke are suspected, the NIHSS should be performed. 
Clinical Laboratory Tests: 
• 
WBC, Hgb, and platelet count 
• 
PT or INR 
• 
Creatinine 
 
 
Discharge 
Discharge is the actual date and time the subject is discharged.  For subjects discharged within 
48 hours of exiting the procedure room, it is not required to repeat tests collected during the Post-

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Procedure period that are also required for the discharge visit.  If the subject was discharged over 
a weekend or holiday, the discharge assessments may be completed on the last weekday prior 
to discharge. 
The following assessments will be conducted within 24 hours of the date and time of discharge. 
Systems: 
• 
Physical assessment (weight, blood pressure and heart rate only) 
• 
Medications:  Antithrombotics only 
• 
Adverse Events 
Cardiopulmonary: 
• 
NYHA functional class 
• 
TTE 
Neurological: 
• 
NIHSS 
All subjects should be assessed to determine if there is evidence of neurological impairment.  If 
symptoms of stroke are suspected, the NIHSS should be performed. 
Clinical Laboratory Tests: 
• 
WBC, Hgb, and platelet count 
• 
PT or INR 
• 
Creatinine 
 
 
Follow-up 
The day of the procedure will be considered Day 0 and will be used to schedule all subsequent 
visits and calculate visit windows. 
 
30 Days (+ 7 days) 
The following assessments will be conducted: 
Systems: 
• 
Physical assessment (weight, blood pressure and heart rate only 
• 
Medications:  Antithrombotics only 
• 
Adverse Events 
Cardiopulmonary: 
• 
NYHA functional class 
• 
12-lead ECG 
• 
TTE 

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Neurological: 
• 
NIHSS 
• 
mRS 
• 
MMSE 
Clinical Laboratory Tests: 
• 
WBC, Hgb, and platelet count 
• 
Creatinine 
Functional: 
• 
6MWT 
• 
QoL Questionnaires 
o KCCQ 
o EQ-5D-5L 
o SF-36 
 
 
1 Year (+ 30 days) 
The following assessments will be conducted: 
Systems: 
• 
Physical assessment (weight, blood pressure and heart rate only) 
• 
Medications:  Antithrombotics only 
• 
Adverse Events 
Cardiopulmonary: 
• 
NYHA functional class 
• 
12-lead ECG 
• 
TTE 
Neurological: 
• 
MMSE 
The following assessments should be completed for all subjects diagnosed with stroke after the 
procedure: 
• 
NIHSS 
• 
mRS 
Functional: 
• 
6MWT 
• 
QoL Questionnaires 

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o KCCQ 
o EQ-5D-5L 
o SF-36 
 
 
2 through 5, 7 and 10 years (+ 45 days) 
The following assessments will be conducted annually: 
• 
Adverse Events 
• 
TTE 
 
 
6, 8 and 9 years (+ 45 days) 
Adverse events will be assessed annually by telephone or office visit. 
 
Imaging Assessments 
Imaging performed during the course of the study should follow imaging manual of operations: 
• 
Echo Manual of Operations 
• 
CT Manual of Operations 
 
 
Neurological Assessments 
Every effort should be made to have a neurologist (or neurology fellow) perform the NIHSS and 
mRS assessments.  If it is not possible to have the neurologist/fellow perform the assessments 
within the protocol-specified visit window, a certified study team member may perform the 
assessments.  For all subjects diagnosed with a new stroke after the procedure start, a follow-up 
mRS assessment should be performed 90 days (± 30 days) after stroke onset to assess stroke 
disability (visit or phone assessment is acceptable).  If the 90-day post-stroke assessment is 
scheduled to occur within 30 days of a protocol-specified visit, the mRS does not need to be 
repeated. 
 
QoL Questionnaires 
QoL will be measured through the following standard surveys: 
1. KCCQ is an assessment of disability and quality of life impairment due to congestive heart 
failure. 
2. EQ-5D-5L is a standardized questionnaire for describing and valuing subjects’ health- related 
quality of life for clinical and economic appraisal. 
3. The SF-36 is a generic health status instrument and rating scale that allows mapping of health 
status to population-level utility weights.  This is an important metric for cost- effectiveness 
analysis. 
Sites will be provided with paper QoL questionnaires (KCCQ, EQ-5D-5L, and the SF-36).  Subject 
questionnaires will be IRB/EC-approved prior to subject administration. 

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Investigational staff will administer subject questionnaires to study subjects.  Subjects will be 
instructed to complete each questionnaire at visits specified in Section 7.  Investigational sites 
should retain the completed questionnaire in the subjects’ source documents. 
 
Subject Discontinuation 
Every subject should be encouraged to remain in the study until they have completed the protocol 
required follow-up.  Site personnel should make all reasonable efforts to locate and communicate 
with the subject at each visit time point.  If the subject has missed multiple visits (with multiple 
attempts to contact), the subject may be considered lost-to-follow-up. 
Subjects are considered discontinued when they leave the study after they have been enrolled.  
Potential reasons for early discontinuation include: 
• 
Study Device Never Implanted:  Subjects considered enrolled but did not receive a study 
valve will be followed for 30 days or until resolution of any adverse events related to the 
valve implant procedure and then exited from the study. 
• 
Study Device Explanted:  Subjects who have a surgical reintervention where the 
CENTERA valve is explanted will be followed for 30 days post-reintervention or until 
resolution of any adverse events related to the procedure and then exited from the study.  
Note:  Subjects that have a BAV or valve-in-valve procedure will continue to be followed 
for the duration of the study. 
If a subject discontinues prematurely, all attempts should be made to have the subject come into 
the clinic for an exit visit to complete the assessments that would have occurred at the next 
scheduled visit.  At a minimum, a telehealth visit should occur to assess adverse events.  An exit 
form indicating the reason for discontinuation will be completed for all subjects.  Subjects who 
discontinue prematurely will be included in the analysis of results and will not be replaced. 
For subjects that are lost-to-follow-up or withdraw early, Edwards may request the site to search 
the Social Security Death Index and/or other death registries and may request the site to obtain 
the death certificate, if applicable. 
 
 

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Table 10 summarizes the subject assessments at each time point. 
Table 10: Schedule of Assessments 
Screening 
Procedure 
Post-Procedure 
Discharge 
30 Days 
1 Year 
2-5, 7, 10 Years 
6, 8, 9 Years p 
Visit Window (days) 
- 30 a 
 
+ 2 o 
 
+ 7 
+ 30 
+ 45 
+ 45 
Informed Consent 
X 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
Physical Assessment 
X 
 
 
X 
X 
X 
 
 
Medications: Antithrombotics 
X 
X 
X 
X 
X 
X 
 
 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
X 
STS Risk Score 
X 
 
 
 
 
 
 
 
EuroSCORE II 
X 
 
 
 
 
 
 
 
TAVR Risk Score 
X 
 
 
 
 
 
 
 
NYHA Functional Class 
X 
 
 
X 
X 
X 
 
 
CCS Angina 
X 
 
 
 
 
 
 
 
12-lead ECG 
X 
 
X 
 
X 
X 
 
 
TTE 
X b 
 
 
X c 
X c 
X c 
X c 
 
TTE/Aortogram or TEE 
 
X 
 
 
 
 
 
 
3D Cardiac Imaging (CT, TEE or cMRI) 
X d 
 
 
 
 
 
 
 
Iliofemoral CT Angiography 
X d 
 
 
 
 
 
 
 
Left Heart Catheterization 
X d 
 
 
 
 
 
 
 
Pulmonary Function Test 
X e 
 
 
 
 
 
 
 
SYNTAX Score 
X f 
 
 
 
 
 
 
 
NIHSS g 
X 
 
X h 
X h 
X 
X i 
 
 
mRS g,h 
X 
 
 
 
X 
X i 
 
 
MMSE 
X 
 
 
 
X 
X 
 
 
WBC, Hgb, Platelet Count 
X 
 
X 
X 
X 
 
 
 
PT or INR 
X 
 
X 
X 
 
 
 
 
CK/CKMB and/or Troponins 
X j 
 
 
 
 
 
 
 
eGFR 
X 
 
 
 
 
 
 
 
Creatinine 
X 
 
X 
X 
X 
 
 
 
Albumin, Total Bilirubin 
X 
 
 
 
 
 
 
 
AST/ALT 
X k 
 
 
 
 
 
 
 
Pregnancy test 
X l 
 
 
 
 
 
 
 
Frailty Index 
X m 
 
 
 
 
 
 
 
6MWT 
X 
 
 
 
X 
X 
 
 

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Table 10: Schedule of Assessments 
Screening 
Procedure 
Post-Procedure 
Discharge 
30 Days 
1 Year 
2-5, 7, 10 Years 
6, 8, 9 Years p 
Visit Window (days) 
- 30 a 
 
+ 2 o 
 
+ 7 
+ 30 
+ 45 
+ 45 
KCCQ 
X 
 
 
 
X 
X 
 
 
EQ-5D-5L 
X 
 
 
 
X 
X 
 
 
SF-36 
X 
 
 
 
X 
X 
 
 
Case Review 
X n 
 
 
 
 
 
 
 
Valve Implant Procedure 
 
X 
 
 
 
 
 
 
a. Screening assessments will be completed within 30 days prior to valve implant procedure, unless otherwise noted. 
b. Must be performed within 90 days prior to the valve implant procedure. 
c. Must be performed per Echo Manual of Operations. 
d. Must be performed within 1 year prior to the valve implant procedure. 
e. Only for subjects with a history of lung disease. 
f. 
Only for subjects with significant native CAD. 
g. Every effort should be made to have a neurologist (or neurology fellow) perform the NIHSS and mRS assessments.  If it is not 
possible to have the neurologist/fellow perform the assessments within the protocol-specified visit window, a certified study team 
member may perform the assessments. 
h. All subjects should be assessed to determine if there is evidence of neurological impairment.  If symptoms of a stroke are 
suspected, the NIHSS should be performed.  For all subjects diagnosed with a new stroke after the procedure start, a follow-up 
mRS assessment should be performed 90 days (± 30 days) after stroke onset to assess stroke disability (visit or phone 
assessment is acceptable). 
i. 
Only for subjects diagnosed with a stroke after the procedure. 
j. 
Required ≤ 72 hours before the valve implant procedure. 
k. Only required for subjects with chronic liver disease. 
l. 
Only for female subjects of childbearing age (urine or serum) 
m. Includes activities of daily living, 5 meter walk test, grip strength and albumin. 
n. Case Review will be completed when all screening procedures have been completed, all inclusion/exclusion criteria have been 
fundamentally confirmed and the site is ready to present a case. 
o. Post-procedure time period is defined as the 48 hours after the subject exits the procedure room. 
p. Can be done by telephone or office visit. 
 
 

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8 ADVERSE EVENTS 
 
Adverse Event Definitions 
An Adverse Event (AE) is any untoward medical occurrence, unintended disease or injury or 
untoward clinical signs (including abnormal laboratory findings) in subjects, users or other 
persons, whether or not related to the investigational medical device. 
AEs may be volunteered by subjects, elicited or collected via observation by the Investigator or 
designee or discovered by review of clinical records by the CEC, Edwards Safety team or 
Edwards Monitoring team.  In addition, subjects will be instructed to contact the Investigator 
and/or study coordinator if any significant AEs occur between study visits. 
All relevant AEs will be reported by the Investigator and reviewed by Edwards in compliance with 
applicable regulations as indicated below Section 8.3. 
A Serious Adverse Event (SAE) is any adverse event that: 
• 
Led to death; 
• 
Led to a serious deterioration in the health of the subject that: 
o Resulted in a life-threatening illness or injury; 
o Resulted in a permanent impairment of a body structure or a body function; 
o Required inpatient hospitalization or prolongation of existing hospitalization; 
o Resulted in medical or surgical intervention to prevent permanent impairment to body 
structure or a body function; 
• 
Led to fetal distress, fetal death or congenital abnormality or birth defect; 
• 
Significant medical event:  Important medical events that do not meet the above criteria 
may still be considered an SAE if they seriously jeopardize the subject and require 
immediate medical or surgical intervention to prevent one of the aforementioned 
outcomes. 
 
An anticipated AE is identified as a potential risk associated with the overall procedure or 
investigational device as stated in the IFU. 
An Unanticipated Adverse Device Effect (UADE) is 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 problem associated with a device that relates to the rights, safety or welfare 
of subjects. 
 
Investigator Assessment of AEs 
If it is determined that an AE has occurred, the Investigator should obtain all the information 
required to complete the AE eCRF. 

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For each AE, the Investigator will determine whether the event is related to the device and/or the 
implant procedure, whether it was anticipated or not anticipated (based on the list of potential 
risks provided in Section 9.2) and whether the event meets the definition of an SAE or UADE as 
outlined in Section 8.1. 
The causal relationship of the event to the device and the implant procedure will be categorized 
as follows: 
• 
None:  The event is not associated with the device or implant procedure.  There is no 
relation between the event and the device or implant procedure. 
• 
Unlikely Related:  The temporal sequence between the device or implant procedure and 
the event is such that the relationship is unlikely but not impossible or there is contradicting 
evidence that can provide plausible explanation of the study subject’s condition. 
• 
Possibly Related:  The temporal sequence between the device or implant procedure and 
the event is such that the relationship is not unlikely or there is no contradicting evidence 
that can reasonably explain the study subject’s condition.  There is a possibility of any 
relation between the event and the device or implant procedure. 
• 
Definitely Related:  The temporal sequence is relevant or the event abates upon device 
removal or the event cannot be reasonably explained by the subject’s condition or 
comorbidities.  The event is related or most likely associated with the device or implant 
procedure. 
 
All AEs must be followed until resolution or until a stable clinical outcome is reached or until the 
subject has exited the study. 
 
AE Reporting Requirements 
All AEs will be captured from the time of enrollment (start of valve implant procedure) through 1 
year post-procedure .  After 1 year post-procedure, only following events need to be captured: 
• 
All AEs related to outcomes 
• 
All AEs that are assessed or suspected to be device or implant procedure related 
• 
All AEs that meet the criteria for an SAE irrespective of device or implant procedure 
relationship 
• 
All AEs considered to be a UADE 
See Section 8.3.1 for events that are not required to be reported to Edwards. 
Pre-existing medical conditions or symptoms reported prior to subject enrollment will not be 
recorded as an AE.  In the event there is a worsening in the pre-existing medical condition that is 
relevant to the subject’s clinical course related to the treatment of their AS or symptoms due to 
the device or study related procedure, then an AE must be recorded. 
Death should not be recorded as an adverse event, but should be reflected as an outcome to 

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another specific AE. 
All relevant AEs, SAEs and UADEs must be reported to Edwards as soon as practical but no 
later than 10 working days of awareness.  Information must be entered into the EDC or when 
EDC is not available, reported via email to THV_Safety@edwards.com, copying the Edwards 
Safety Officer of the study. 
At the time of initial notification, the following minimal information must be provided: 
• 
Study site 
• 
Subject ID 
• 
AE description 
• 
Causal relationship to study device and implant procedure 
• 
Aware date 
 
The site will provide a copy of supporting documentation (example: admission history & physical, 
implant procedure reports, anesthesia records, discharge summary, echocardiogram and ECG 
reports, laboratory results, etc.) for all events related to endpoints and outcomes (see Section 5), 
device malfunctions, device- and procedure-related events and UADEs to Edwards (or designee).  
Source documentation may be requested by the Edwards Safety Officer for other AEs and SAEs 
on a case-by-case basis. 
Enrolling sites must send to Edwards Clinical Safety, at a minimum, an admission history and 
physical, valve implant procedure report and discharge summary from index hospitalization along 
with relevant labs, echocardiographic and ECG reports for each subject enrolled in the study.  
This will be done irrespective of subject having any AE/SAE. 
The Investigator is responsible for notifying the IRB/EC of SAEs, UADE and/or AEs, as required; 
UADEs must be reported as soon as practical but no later than 10 working days after the 
Investigator first learns of the effect and submitting any additional information as required by 
IRB/EC, local regulations, Edwards or FDA.  A copy of all IRB/EC reports should be provided to 
Edwards (or designee). 
Edwards will notify the FDA as well as all participating clinical Investigators and IRBs/ECs of all 
UADEs that occur during this study within 10 working days after becoming aware of the event.  
Investigators are responsible for reviewing information received about UADEs. 
 
Events that do not require reporting to the Sponsor 
For purposes of this study, the following events will not be required to be reported as AEs to 
Edwards, because they are normally expected to occur in conjunction with transcatheter valve 
implantation or are associated with customary, standard care of subjects undergoing THV 
implantation: 
• 
Post-operative pain 

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• 
Post-anesthesia emesis, nausea or headache (within 24 hours of procedure) 
• 
Electrolyte imbalance without clinical sequelae following procedure, even if requiring 
correction 
• 
Pre-planned future surgical procedures not associated with the study procedure or device 
• 
Low grade temperature increase (≤ 101°F or 38.5°C) 
• 
Dizziness: Imprecise term commonly used to describe various symptoms such as 
faintness, giddiness, imbalance, lightheadedness, unsteadiness or vertigo without signs 
of TIA or stroke. 
• 
Elevated WBC, outside the standard laboratory normal value, without signs and symptoms 
of infection 
• 
Minor, localized tenderness, swelling, induration, oozing, etc. at incision / delivery system 
insertion site 
• 
Systolic or diastolic blood pressure changes that do not require treatment or intervention 
• 
Thrombocytopenia: does not become an AE until treatment is administered; suspected 
heparin-induced thrombocytopenia should be reported. 
• 
Hyperglycemia – The use of insulin in the post-operative period does not constitute 
hyperglycemia if during the index hospitalization.  An elevated blood sugar of less than 
250 mg/dL during the first 48 hours post-operative does not constitute hyperglycemia. 
• 
Expected, non-clinically significant events such as non-significant lab variances. 
 
 
Sponsor Assessment of AEs 
All AEs will be reviewed by the Edwards Safety Officer.  Each AE will be assessed as to its 
relationship to the study device and/or implant procedure, whether it was anticipated or not 
anticipated (based on the list of potential risks provided in Section 9.2) and whether it qualifies 
as an SAE or UADE as outlined in Section 8.1. 
 
Device Malfunctions 
A device malfunction is defined as the failure of a device to meet its performance specifications 
or otherwise perform as intended.  Performance specifications include all claims made in the 
labeling for the device.  The intended performance of a device refers to the intended use for which 
the device is labeled. 
Device malfunctions should be reported to Edwards as soon as practical but no later than 10 
working days of the site awareness of these malfunctions. 

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9 RISKS AND BENEFIT ANALYSIS 
 
Potential Benefits 
There are no guaranteed benefits from participation in this study.  Information gained from this 
study may be of benefit to other people with the same medical condition in the future.  The long-
term results of using the CENTERA THV are not known at the present time.  Alternative 
treatments include other TAVR devices, surgical AVR and BAV. 
Implantation of the CENTERA THV may result in improved valvular function, acute alleviation of 
symptoms related to AS, and improved quality of life in patients with intermediate operative risk 
of mortality. 
 
Potential Risks 
The potential risks associated with this study can be grouped into two categories.  First, there are 
the potential risks related to the overall procedure (standard cardiac catheterization, BAV and use 
of anesthesia).  Second, there are the additional potential risks associated with the use of the 
CENTERA THV System. 
Potential risks associated with standard cardiac catheterization, BAV and use of anesthesia 
include but are not limited to: 
• 
Abnormal lab values (including 
electrolyte imbalance) 
• 
Acute myocardial infarction 
• 
Allergic reaction to device materials, 
antithrombotic therapy or contrast 
medium or anesthesia 
• 
Anemia 
• 
Aneurysm 
• 
Angina 
• 
Arrhythmias including ventricular 
fibrillation (VF) and ventricular 
tachycardia (VT) 
• 
Arteriovenous fistula 
• 
Arthralgia 
• 
Bleeding/bruising 
• 
Cardiovascular injury including 
perforation or dissection of vessels, 
ventricle, myocardium or valvular 
structures that may require 
intervention 
• 
Conduction system defect which 
may require a permanent 
pacemaker 
• 
Cardiogenic shock/pulmonary 
edema 
• 
Cerebrovascular accident 
• 
Death 
• 
Dissection: aortic or other vessels 
• 
Embolization including air, calcific 
valve material, or thrombus 
• 
Exercise intolerance or weakness 
• 
Fever 
• 
GI symptoms 
• 
Headache 
• 
Heart failure 
• 
Hematologic dyscrasia 
• 
Heart murmur 
• 
Hematoma 
• 
Hemorrhage requiring transfusion or 
intervention 
• 
Hemorrhagic stroke 
• 
Hepatic enzyme changes 
• 
Hypotension or Hypertension 
• 
Infection including septicemia and 
endocarditis 

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• 
Inflammation 
• 
Ischemia or nerve injury 
• 
Limb ischemia 
• 
Myocardial infarction 
• 
Myalgia 
• 
Pain or changes at the access site 
• 
Paralysis 
• 
Perforation or rupture of cardiac 
structure 
• 
Perforation or rupture of vessel 
• 
Pericardial effusion/cardiac 
tamponade 
• 
Permanent disability 
• 
Peripheral nerve injury/paralysis 
• 
Postoperative encephalopathy 
• 
Pleural effusion 
• 
Pulmonary edema 
• 
Pseudoaneurysm 
• 
Renal insufficiency or renal failure 
• 
Reoperation 
• 
Respiratory insufficiency or 
respiratory failure 
• 
Restenosis 
• 
Retroperitoneal bleed 
• 
Shock 
• 
Silent cerebral ischemia 
• 
Stroke/transient ischemic attack, 
clusters or neurological deficit 
• 
Syncope 
• 
Thoracic bleeding 
• 
Vasovagal response 
• 
Vessel spasm 
• 
Vessel thrombosis/occlusion 
• 
Vessel trauma requiring surgical 
repair or intervention 
 
In addition to the risks listed above, additional potential risks specifically associated with AVR and 
bioprosthetic heart valves include, but may not be limited to: 
• 
Acute coronary occlusion 
• 
Allergic/immunologic reaction to the 
implant 
• 
Aortic annulus 
dissection/rupture/trauma 
• 
Aortic valve insufficiency 
• 
Aortic valve thrombosis/occlusion 
• 
Atrial fibrillation/Atrial flutter 
• 
Arteriovenous block 
• 
Blood loss requiring blood 
transfusion 
• 
Cardiac arrest 
• 
Cardiac failure or low cardiac output 
• 
Cardiogenic shock 
• 
Cognitive impairment 
• 
Conduction disturbance including AV 
block requiring pacemaker 
• 
Device degeneration 
• 
Device embolization 
• 
Device explants 
• 
Device migration or malposition 
requiring intervention 
• 
Device thrombosis requiring 
intervention 
• 
Device malfunction requiring 
intervention/surgery 
• 
Emergency cardiac surgery 
• 
Endocarditis 
• 
Hemolysis 
• 
Injury to aortic and/or mitral valve 
• 
Mechanical failure of delivery 
system, and/or accessories 
• 
Mediastinitis 
• 
Mediastinal bleeding 
• 
Mitral regurgitation 
• 
Non-emergent reoperation 
• 
Nonstructural dysfunction 
• 
Peri-/Paravalvular leak/regurgitation 
(moderate to severe)  
• 
Structural valve deterioration (wear, 

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fracture, calcification, leaflet 
tear/tearing from the stent posts, 
leaflet retraction, thickening, 
stenosis) 
• 
Valve deployment in unintended 
location 
• 
Valve regurgitation 
• 
Valve stenosis 
• 
Valve thrombosis 
 
 
 
Risk Minimization 
Product handling and implant procedure guidance are provided in the IFU and training manual, 
which will be used for device training to minimize risks associated with device use.  All cases will 
be reviewed and approved prior to enrollment to confirm that the subject is an appropriate 
candidate for the investigational devices and Edwards representative(s) will be present during all 
implant procedures to provide device-related guidance.  Additionally, efforts will be made to 
minimize risks through site/investigator selection and study management.  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. 
10 STATISTICAL ANALYSIS 
 
Analysis Populations 
• 
The All Treated (AT) population is defined to include all enrolled subjects (see Section 
7.3), whether or not the index procedure is completed. 
• 
The Valve Implant (VI) population is the subset of the AT population consisting of all 
subjects who receive and retain the CENTERA valve upon leaving the procedure room.  
Subjects who are converted to SAVR during the procedure will not be part of the VI 
population. 
Roll-in subjects will not be pooled with enrolled subjects for data analysis and will not be counted 
towards the enrolled sample size. 
 
General Statistical Methodology 
The study outcomes will be summarized with descriptive statistics as described below.  No 
hypothesis testing will be performed. 
• 
Time-to-event variables will be analyzed using the KM algorithm, with standard errors 
computed by Greenwood’s formula.  The number of subjects-at-risk will be computed at 
exact time points, without reference to any nominal follow-up windows. 
• 
For continuous variables, summary statistics will include means, standard deviation and 
sample size. 
• 
For ordinal variables, summary statistics will include counts and percentages and will be 
presented when appropriate. 
• 
For categorical variables, summary statistics will include counts and percentages. 
 

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11 STUDY ADMINISTRATION 
 
General Study Organization 
Edwards 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 will be responsible for obtaining Investigational Device Exemption (IDE) approval for the 
study, selecting investigators, ensuring that sites have IRB/EC approval prior to device shipment, 
and conducting clinical site monitoring to ensure that subjects are being properly consented and 
the study is being conducted according to the protocol.  Edwards will notify investigative sites of 
enrollment closure. 
As appropriate, Edwards will submit changes in the Investigational Plan to the FDA and 
Investigators to obtain IRB/EC re-approval. 
Edwards will maintain copies of correspondence, data, shipment of devices, adverse device 
effects and other records related to the clinical study as appropriate. 
Edwards will submit all reports required by the FDA as identified in Title 21 Code of Federal 
Regulations (CFR) Part 812.150(b).  This includes UADEs, withdrawal of IRB/EC approval, 
current investigators list, annual progress reports, recall information, final reports and protocol 
violations. 
 
Steering Committee 
A Steering Committee will be selected to provide oversight and medical expertise to the study.  
Steering Committee activities will be defined in the Steering Committee Charter.  Steering 
Committee activities ceased after enrollment closure. 
 
Case Review Board 
The Case Review Board is comprised of a subset of Investigators who are participating in the 
study.  The role of the Case Review Board is to review submitted cases to determine if the subject 
is an appropriate candidate for the study, with a focus on confirming subject operative risk, valve 
sizing, appropriate vascular access, valve morphology and any relevant clinical factors impacting 
enrollment eligibility.  Case Review Board activities ceased after enrollment closure. 
 
Data Safety Monitoring Board 
An independent Data Safety Monitoring Board (DSMB) will review study data, evaluate trends in 
reported adverse events and any potential changes in risk assessment, and make 
recommendations to Edwards regarding safety issues and risks to research subjects as well as 
the continuing validity and scientific merit of the study.  DSMB activities are defined in the DSMB 
Charter.  DSMB activities ceased after enrollment closure. 

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Clinical Events Committee 
The CEC will adjudicate endpoint and outcome-related events (see Section 5) and provide 
assessment of SAEs and device/procedure-relatedness from enrollment through the primary 
endpoint.  CEC activities are defined in the CEC Charter.  CEC activities ceased after enrollment 
closure. 
 
Echocardiographic Core Lab 
Study subjects will receive an echocardiogram at the visits specified in Section 7.  An 
echocardiographic core lab will be established to independently review and analyze 
echocardiographic images.  A standardized protocol for acquiring images will be developed by 
the core lab and be provided to the clinical sites prior to study initiation.  Sites will be trained on 
acquiring images prior to study initiation. 
 
Computed Tomography Core Lab 
Study subjects will have a CT at the visits specified in Section 7.  A CT core lab will be established 
to independently review and analyze CT images (and MRI images, if any).  A standardized 
protocol for acquiring images will be developed by the core lab and be provided to the clinical 
sites prior to study initiation.  Sites will be trained on acquiring images prior to study initiation. 
 
Image Management 
An image transfer vendor will be established to receive, maintain and provide cardiac images 
(echocardiogram and CT) to the appropriate core lab for analysis. 
Instructions for image upload will be provided to investigative staff prior to study initiation.  
Investigative staff should upload all images to the image management core lab within 5 business 
days of data collection. 
 
Histopathology 
Histopathology will be performed on all explanted valves.  Explants will be prepared, preserved, 
and shipped to the Histopathology Core Lab per instructions provided by Edwards. 
 Site Personnel Training 
To ensure proper device usage, uniform data collection and protocol compliance, training is 
required for relevant study site personnel in accordance to roles outlined in the DoA log. 
At the beginning of the study, Edwards will provide training to site personnel.  Training will include 
review of the IFU of the device, study protocol, case review process, identification of eligible 
subjects, instructions on data collection, standardized data collection for core laboratory analysis, 
methods for soliciting data from alternative sources and regulatory requirements. 
Ongoing training may be provided in one of the following formats by Edwards or its designee: live 
training sessions, teleconference, WebEx, online or read and review.  Retraining may be 

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performed for sites who have demonstrated protocol or implant procedure compliance issues. 
Documentation of site personnel qualifications and training should be maintained in the site’s 
clinical study files and copies collected and forwarded to Edwards. 
 Device Management 
 Investigational Device 
All investigational devices will be supplied by Edwards.  Unique identifiers associated with any 
device should be recorded in the subject’s medical file as well as on the implant card that is given 
to the subject. 
 Device Storage 
All investigational device components provided for the study should be stored in a secure location 
where only study personnel can access the device for use. 
 Device Accountability 
The study site will maintain detailed records of the receipt and disposition of all investigational 
devices.  Device disposition will be verified by the clinical monitor periodically throughout the 
study.  The Investigator will return unused devices to Edwards along with the completed device 
accountability log at completion of enrollment.  Use of the investigational devices and accessories 
provided for use in this study is prohibited outside of this protocol. 
 Data Management 
Edwards will provide data management through a secure, password protected EDC system 
accessible via the Internet.  A unique Subject ID will be assigned for each subject enrolled in the 
study.  All pertinent data from the subject’s records will be entered by the study site and core lab 
personnel into the eCRFs. 
Every reasonable effort should be made to complete data entry within 5 business days of data 
collection.  Data review by Edwards personnel will occur remotely as well as during on-site 
monitoring.  Data discrepancies will be queried and resolved through the EDC system. 
The site Principal Investigator or designee must ensure the accuracy and completeness of the 
recorded data and then provide his/her electronic signature on the appropriate eCRFs.  Changes 
to data previously submitted to Edwards will require a new electronic signature to 
acknowledge/approve the changes. 
 Monitoring Procedures 
All clinical sites will be monitored periodically by Edwards or designee to ensure compliance with 
the protocol and the Investigator’s Agreement and that all study subjects have been properly 
consented.  The monitor will ensure that the completed eCRFs match the source documents and 
work with the site to resolve differences through electronically generated queries or formal action 
items. 

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Edwards 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. 
 Auditing 
The study may be subject to a quality assurance audit by Edwards or a designee, as well as 
inspection by appropriate regulatory authorities.  It is important that the Investigator and relevant 
study personnel are available during any audits and that sufficient time is devoted to the process.  
In the event of an audit by regulatory authorities, the Investigator should contact Edwards as soon 
as possible. 
 Publication Policy 
Publication or presentation of the overall clinical study results and/or site-specific results requires 
prior written approval of Edwards.  If Edwards approves the publication or presentation of the 
overall clinical study results and/or site-specific results, then Institutions and Investigators will 
comply with the Publications and Public Disclosure Section of the Clinical Trial Agreement.  
Edwards will provide statistical support for the publication process. 
The study results will be made public within 24 months of the end of data collection and a full 
report of the outcomes will be made public no later than three (3) years after the end of data 
collection. 
12 ETHICAL AND REGULATORY CONSIDERATIONS 
 
Applicable Regulations 
This study will be conducted in compliance with the Title 21 CFR Parts 50, 56, 812, and Good 
Clinical Practices (GCP). 
 
Institutional Review Board 
This protocol, the proposed ICF, other written subject information and any proposed advertising 
material must be submitted to the IRB/EC for written approval.  A copy of the written IRB/EC 
approval of the protocol and ICF must be received by Edwards before recruitment of subjects into 
the study and shipment of investigational product. 
The Investigator must submit and, where necessary, obtain approval from the IRB/EC for all 
subsequent protocol amendments and changes to the ICF. 
The Investigator is responsible for obtaining annual IRB/EC approval and renewal throughout the 
duration of the study.  Copies of the Investigator’s reports and the IRB/EC continuance of approval 
must be sent to Edwards. 
 
Informed Consent 
Edwards will provide a sample ICF to the Investigator to prepare for use at his/her site.  The site-
specific ICF, and any subsequent modifications, must be in agreement with current regulations 

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and guidelines and must be approved by Edwards prior to submission to the IRB/EC.  The 
reviewing IRB/EC must approve the ICF before use at the site. 
Before participating in the clinical study, each subject must give written Informed Consent after 
the context of the study has been fully explained in a language that is easily understood by the 
subject.  The subject must also be given the opportunity to ask questions and have those 
questions answered to his/her satisfaction. 
A copy of each subject’s signed and dated consent form must be maintained by each Investigator 
in a designated clinical study administrative file.  A signed copy of the consent form must be given 
to each subject.  The consent process must be documented in the subject’s medical chart. 
 
Confidentiality 
All data used in the analysis and reporting of this evaluation will be without identifiable reference 
to the subject.  Authorized personnel assigned by Edwards will have access to the confidential 
files and will have the right to inspect and copy all records pertinent to this study. 
 
Investigator Records 
Records to be maintained by the Investigator include, but are not limited to, the following: 
• 
Clinical study protocol and all amendments 
• 
Signed Clinical Trial Agreement and any amendments 
• 
IRB/EC approval letters, including continuing reviews and all amendments/changes 
• 
IRB/EC approved informed consent documents 
• 
All correspondence with another Investigator, IRB/EC, sponsor, monitor or FDA, 
including required reports 
• 
Records of receipt, use or disposition of a device 
 
The following records must be maintained for each subject enrolled in the study: 
• 
Signed ICF 
• 
All relevant source documentation for study visits and study-related procedures 
• 
Supporting documentation of any AEs 
 
All clinical sites will maintain the study records for a period of two years after the latter of the 
following two dates:  The date on which the investigation is terminated or completed, or the date 
that the records are no longer required for purposes of supporting a premarket approval 
application. 
 
Investigator Reports 
In addition to AE reporting requirements discussed in Section 8.3, the following reports are 

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required: 
• 
Withdrawal of IRB/EC Approval.  Within 5 working days, the Principal Investigator will 
report a withdrawal of approval by the reviewing IRB/EC of the Investigator’s part of an 
investigation to Edwards. 
• 
Informed Consent.  If an Investigator uses a device without obtaining informed consent, 
the Investigator shall report such use to Edwards and the reviewing IRB/EC within 5 
working days after the use occurs. 
• 
Progress Reports.  The Principal Investigator will submit progress reports on the 
investigation to Edwards and the IRB/EC at least yearly. 
• 
Final Report.  Upon completion or termination of this Study, the Principal Investigator must 
submit a final written report to Edwards and the IRB/EC as required by the regulations.  
The report must be submitted within 3 months of completion or termination of the study. 
 
Amending the Protocol 
This protocol must be followed exactly.  It can be altered only by written amendments made by 
Edwards.  The amended protocol will be submitted to the required regulatory agencies before 
being distributed to all enrolling sites.  Each site must obtain IRB/EC approval, complete required 
training (if any, and as required by DoA role), and receive written approval from Edwards before 
implementing the revised protocol. 
 
Protocol Deviations 
An Investigator must not make any changes or deviate from this protocol, except to protect the 
life and physical well-being of a subject in an emergency.  Emergency changes to protect the life 
of the subject do not require prior approval but must be reported to Edwards and the reviewing 
IRB/EC within 5 days of the incident. 
Each deviation from the protocol must be documented with the date and reason for the deviation 
and reported to Edwards as soon as possible, and to the IRB/EC per local guidelines and 
government regulations. 
 
 

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APPENDIX A. ABBREVIATIONS 
Abbreviation 
Full Term 
6MWT 
Six-Minute Walk Test 
ACC 
American College of Cardiology 
ACT 
Activated Clotting Time 
AE 
Adverse Event 
AHA 
American Heart Association 
AKI 
Acute Kidney Injury 
ALT 
Alanine Aminotransferase 
ANOVA 
Analysis of Variance 
AR 
Aortic Regurgitation 
AS 
Aortic Stenosis 
ASA 
Aspirin 
AST 
Aspartate Aminotransferase 
AT 
All Treated 
ATT 
Average Treatment effect for the Treated 
AV 
Aortic Valve 
AVA 
Aortic Valve Area 
AVR 
Aortic Valve Replacement 
BAV 
Balloon Aortic Valvuloplasty 
BMI 
Body Mass Index 
BMS 
Bare Metal Stent 
CABG 
Coronary Artery Bypass Graft 
CAD 
Coronary Artery Disease 
CCS 
Canadian Cardiovascular Society 
CEC 
Clinical Events Committee 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
CK 
Creatine Kinase 
CKMB 
Creatine Kinase MB Isoenzyme 
COPD 
Chronic Obstructive Pulmonary Disease 
CT 
Computed Tomography 
DES 
Drug Eluting Stent 
DM 
Diabetes Mellitus 
DoA 
Delegation of Authority 
DSMB 
Data Safety Monitoring Board 
EACTS 
European Association for Cardio-Thoracic Surgery 
EC 
Ethics Committee 
ECG 
Electrocardiogram 

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Abbreviation 
Full Term 
eCRF 
Electronic Case Report Form 
eGFR 
Estimated Glomerular Filtration Rate 
EDC 
Electronic Data Capture 
EOA 
Effective Orifice Area 
EQ 
EuroQol 
ESC 
European Society of Cardiology 
ExCEED 
A Prospective, Single-arm, Controlled, Multicenter Study to Establish the Safety 
and Effectiveness of the CENTERA THV System in IntermEDiate Risk Patients 
who have Symptomatic, Severe, Calcific, Aortic Stenosis Requiring Aortic Valve 
Replacement 
FEV1 
Forced Expiratory Volume in 1 Second 
FDA 
Food and Drug Administration 
Hgb 
Hemoglobin 
HOCM 
Hypertrophic Obstructive Cardiomyopathy 
ICF 
Informed Consent Form 
ICU 
Intensive Care Unit 
IDE 
Investigational Device Exemption 
IFU 
Instructions for Use 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
KCCQ 
Kansas City Cardiomyopathy Questionnaire 
KM 
Kaplan-Meier 
LA 
Left Atrial 
LMW 
Low Molecular Weight 
LVEF 
Left Ventricular Ejection Fraction 
MACCE 
Major Adverse Cardiovascular and Cerebrovascular Events 
MI 
Myocardial Infarction 
MMSE 
Mini Mental State Examination 
MR/MRI 
Magnetic Resonance / Magnetic Resonance Imaging 
mRS 
Modified Rankin Scale 
NIHSS 
National Institutes of Health Stroke Scale 
NYHA 
New York Heart Association 
OPG 
Objective Performance Goal 
PARTNER 
Placement of AoRtic TranNscathetER 
PCI 
Percutaneous Coronary Intervention 
PET 
Polyethylene Terephthalate 
Plt 
Platelets 
PPM 
Patient Prosthesis Mismatch 
PT 
Prothrombin Time 
PVL 
Paravalvular Leak 

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Abbreviation 
Full Term 
QD 
Every Day / Daily 
QoL 
Quality of Life 
SAVR 
Surgical Aortic Valve Replacement 
SAE 
Serious Adverse Event 
SF 
Short Form 
STS 
Society of Thoracic Surgeons 
SVD 
Structural Valve Deterioration 
TAVR 
Transcatheter Aortic Valve Replacement 
TEE 
Transesophageal Echocardiogram 
THV 
Transcatheter Heart Valve 
TIA 
Transient Ischemic Attack 
TTE 
Transthoracic Echocardiogram 
UADE 
Unanticipated Adverse Device Effect 
UF 
Unfractionated Heparin 
VF 
Ventricular Fibrillation 
VI 
Valve Implant 
VT 
Ventricular Tachycardia 
WBC 
White Blood Cell 
 
 

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APPENDIX B. DEFINITIONS 
Term 
Definition 
Reference/ 
Justification 
6 Minute Walk 
Test (6MWT) 
A performance-based measure of functional exercise capacity.  The 
test measures the distance an individual is able to walk over a total of 
six minutes on a hard, flat surface.  See more at: 
https://www.rheumatology.org/I-Am-
A/Rheumatologist/Research/Clinician-Researchers/Six-Minute-Walk-
Test-SMWT 
ATS 
Access Site 
Any location (arterial or venous) traversed by a guidewire, a catheter 
or a sheath for TAVR 
VARC-1 33 
Access Site 
Related 
Complication 
Any adverse clinical consequence possibly associated with any of the 
access sites used during the procedure 
Planned repair of access site entry portals are not considered access 
site-related complications. 
VARC-1, 
VARC-2 34 
Acute Kidney 
Injury (AKI) 
AKI is defined by an abrupt decrease in kidney function 
• Reportable AKI is for any creatinine with an increase in serum 
creatinine to > 150% of baseline, OR 
• increase of ≥ 0.3 mg/dL compared to baseline within 48 hours of 
index procedure, OR 
• Urine output < 0.5 mL/kg per hour for > 6 but < 12 hours 
Patients receiving renal replacement therapy (dialysis, hemodialysis, 
peritoneal dialysis, hemofiltration, transplant therapy) are considered 
to meet Stage 3 AKI criteria. 
For AKI diagnosis beyond Index Procedure (or for subjects who do 
not get Index Procedure), the same criteria are to be used with a pre-
AKI diagnosis baseline. 
Note:  AKI stage will be determined per VARC-2 criteria. 
AKIN / 
KDIGO / 
VARC-2 / 
Sponsor 
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 medical device 
ISO 14155-
1:2011 
GCP 
Angina / 
Cardiac Chest 
Pain 
Chest pain due to myocardial ischemia caused by an imbalance 
between myocardial blood supply and oxygen demand. 
Sponsor 

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Term 
Definition 
Reference/ 
Justification 
Angina, 
Grading Scale 
Grade 
Description 
I 
Ordinary physical activity, such as walking and climbing stairs, 
does not cause angina.  Angina occurs with strenuous, rapid, or 
prolonged exertion at work or during recreation 
II 
Slight limitation of ordinary activity.  Angina occurs with walking or 
climbing stairs rapidly, walking uphill, walking or stair climbing 
after meals, walking in the cold, into the wind, while under 
emotional stress, or during the first hours after awakening.  
Walking more than two blocks on the level and climbing more 
than one flight of ordinary stairs at a normal pace and in normal 
conditions, does not cause angina 
III 
Marked limitation of ordinary physical activity.  Angina occurs with 
walking one to two blocks on the level and climbing one flight of 
stairs in normal conditions and at a normal pace 
IV 
Inability to carry on any physical activity without discomfort.  
Angina syndrome may be present at rest 
Canadian 
Cardiovascul
ar Society 
Aortic 
Dissection 
Aortic dissection is defined as separation of the layers within the 
aortic wall.  Tears in the intimal layer could have blood entering 
intima-media space resulting in the propagation of dissection 
(proximally or distally). 
Sponsor 
Aortic 
Stenosis, 
Native 
Aortic stenosis is classified as “severe” when the following are 
present: 
• Jet velocity ≥ 4.0 m/s 
• Mean gradient ≥ 40 mmHg 
• Valve area ≤ 1.0 cm2 
• Valve area index ≤ 0.6 cm2/m2 
2014 
AHA/ACC 
Arrhythmia / 
Conduction 
System Injury 
(Defect) 
Arrhythmia: an increased heart rate (> 100 beats/min Tachycardia) or 
decreased heart rate (< 60 beats/min Bradycardia) or an irregular 
heart rate which could result in symptoms or require medical/surgical 
intervention. 
Conduction system defect:  an impairment of Sinoatrial node, 
Atrioventricular node or specialized muscular fibers that conduct 
impulses through the heart (Internodal fibers, Bundle of His, Bundle 
branches, Purkinje fibers). 
Sponsor 

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Term 
Definition 
Reference/ 
Justification 
Atrial 
Fibrillation 
Atrial fibrillation is rapid irregular heart rhythm characterized by rapid 
and irregular beating of atria with or without associated ventricular 
fibrillation and has ECG characteristics of atrial fibrillation and lasts 
sufficiently long to be recorded on a 12-lead ECG, or at least 30 
seconds on a rhythm strip. 
The type of atrial fibrillation includes: 
• Paroxysmal atrial fibrillation:  Atrial fibrillation that terminates 
spontaneously or with intervention within 7 days of onset.  
Episodes may recur with variable frequency. 
• Persistent atrial fibrillation:  Continuous atrial fibrillation that is 
sustained >7 days or requires medical (rate/rhythm control) or 
surgical intervention (Ex: ablation, cardioversion or Maze 
procedure). 
• Permanent AF:  Permanent AF is used when there has been an 
inability to restore and/or maintain sinus rhythm with medical 
and/or surgical intervention. 
Sponsor 35 
Bicuspid 
Aortic Valve 
Bicuspid aortic valve is an inheritable condition where aortic valve 
appears on gross examination with only two cusps as a result of 
fusion during development.  This comprises a spectrum of deformed 
aortic valves presenting with two functional cusps forming a valve 
mechanism with less than three zones of parallel apposition between 
cusps. 
Type 1: valve with one raphe 
Type 2: valve with two raphes 
36 

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Term 
Definition 
Reference/ 
Justification 
Bioprosthetic 
Valve 
Dysfunction 
(BVD) 
Bioprosthetic valve dysfunction (BVD) can be either non-structural or 
structural: 
 
Non-structural causes of BVD (BVD due to extrinsic causes or 
processes unrelated to intrinsic function of valve leaflets) are defined 
as any of the following: 
• Paravalvular leak (PVL) 
• Endocarditis 
• Patient-prosthesis mismatch (moderate or severe per Valve 
Academic Research Consortium-2 (VARC 2) definitions) at 
discharge 
 
Structural BVD should be defined as follows (regardless of whether 
or not findings drive therapy): 
• 
Bioprosthetic valve hemodynamic dysfunction (BVHD) 
• 
Mild BVHD – A > 50% increase in mean gradient from 
discharge, and/or new or progressive mild intra-prosthetic (i.e. 
central) aortic regurgitation (AR).  If the mean gradient is 
greater than 20 or 40 mmHg, categorize as moderate or severe 
BVHD, respectively. 
• 
Moderate BVHD – Mean gradient ≥ 20 mmHg, and/or new or 
progressive moderate intra-prosthetic AR 
• 
Severe BVHD – Mean gradient ≥ 40 mmHg, and/or new or 
progressive severe intra-prosthetic AR 
• 
Bioprosthetic valve structural deterioration (BVSD) 
• 
Anatomic imaging evaluation (echocardiography or CT) or 
autopsy findings demonstrate persistent bioprosthetic leaflet 
pathology related to  
i. 
structure (leaflet tears, etc.) 
ii. 
abnormal thickness without mobility change 
iii. mobility restriction (RLM) 
iv. calcification 
• 
Bioprosthetic Valve Failure (BVF) 
• 
Referral for aortic valve re-intervention (valve-in-valve) or 
reoperation for progressive BVHD and/or BVSD 
• 
Valve-related death 
• 
An unexplained death following diagnosis of BVD in any of the 
above stages 
• 
BVSD observed at autopsy likely related to cause of death 
• 
The presence of severe hemodynamic dysfunction (i.e., mean 
gradient ≥ 40 mmHg, and/or new or progressive severe intra-
prosthetic regurgitation), whether or not the patient is referred 
for reintervention or reoperation 
FDA 

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Term 
Definition 
Reference/ 
Justification 
Bleeding 
Overt bleeding is defined as clinically obvious (visible bleeding and 
bleeding identified by imaging only). 
Examples of overt bleeding include: 
• Pseudoaneurysm 
• Retroperitoneal hematoma seen on CAT scan 
• Visible access site hematoma 
Actionable Bleeding is more bleeding than expected for clinical 
circumstance needing increased level of care like 
• hospitalization 
• medical/surgical intervention 
• transfusions 
Thresholds for reporting procedural bleeding for SAVR procedure is 
bloody chest tube output > 600 mL within any 24-hour period and for 
TF-TAVR >100 mL total EBL (Estimated Blood Loss) from access 
site.  These are suggested as guidelines for Site reporting of 
Bleeding events and clinical judgement should be used in reporting 
bleeding events. 
All post-procedural overt bleeding events must be reported 
including hematuria, melena, hematemesis, occult gastrointestinal 
bleeds or drop in Hgb with overt source of bleeding detected 
requiring transfusions etc. 
If the reason for Hgb drop was other than due to the overt bleeding 
i.e. due to hemodilution, chronic iron deficiency anemia, this will not 
be considered as a bleeding event. 
Note:  Bleeding will be adjudicated per VARC-2 and BARC criteria. 
Sponsor 
CABG 
Coronary artery bypass graft surgery is a procedure performed to 
bypass partially or completely occluded coronary arteries with veins 
(commonly Great/Small Saphenous veins) and/or arteries (commonly 
Internal thoracic/Mammary artery) harvested from elsewhere in the 
body, thereby improving the blood supply to the coronary circulation 
supplying the myocardium (heart muscle). 
Sponsor/ 
2014 
ACC/AHA 
Key Data 
Elements 
and 
Definitions 
for 
Cardiovascu
lar Endpoint 
Events in 
Clinical 
Trials 
Cardiac Arrest 
Cardiopulmonary arrest or circulatory arrest is a sudden stop in 
effective blood circulation due to the failure of the heart to contract 
effectively or at all. 
Sponsor / 
STS 
Cardiac 
Tamponade 
Evidence of a new pericardial effusion associated with hemodynamic 
instability evident by: 
1. Echo showing pericardial fluid and signs of tamponade such as 
right heart compromise, or 
2. Systemic hypotension due to pericardial fluid compromising 
cardiac function 
VARC-2 / 
STS 

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Term 
Definition 
Reference/ 
Justification 
Cardiogenic 
Shock 
Sustained (> 30 min) episode of systolic BP < 90 mmHg and/or 
cardiac index < 2.2 L/min/m2 determined to be secondary to cardiac 
dysfunction, and/or the requirement for parenteral inotropic or 
vasopressor agents or mechanical support (e.g., intra-aortic balloon 
pump, extracorporeal circulatory support, ventricular assist device) to 
maintain BP and cardiac index above those specified levels 
2014 
ACC/AHA 
Key Data 
Elements 
and 
Definitions 
for 
Cardiovascul
ar Endpoint 
Events in 
Clinical Trials 
Cardiopulmon
ary Bypass 
(CPB) 
CPB is a form of extracorporeal circulation that temporarily takes over 
the function of the heart and lungs during surgery, maintaining the 
circulation and oxygen content of blood in the patient's body. 
Sponsor 
Cerebrovascul
ar Disease 
Cerebrovascular disease includes all disorders in which an area of 
the brain is temporarily or permanently affected by ischemia or 
bleeding and one or more of the cerebral blood vessels are involved 
in the pathological process.  It includes: 
• 
Stroke 
• 
TIA 
• 
Noninvasive or invasive arterial imaging test demonstrating 
>=50% stenosis of any of the major extracranial or intracranial 
vessels to the brain  
• 
Previous cervical or cerebral artery revascularization surgery or 
percutaneous intervention 
This does not include chronic (nonvascular) neurological diseases or 
other acute neurological insults such as metabolic and anoxic 
ischemic encephalopathy 
STS 
Congestive 
Heart Failure 
(CHF) 
Heart failure develops when the heart due to an abnormality of 
cardiac function (detectable or not), fails to pump blood at a rate 
commensurate with the requirements of the metabolizing tissues or is 
able to do so only with an elevated diastolic filling pressure. 
Diagnosis requires physician documentation or report of clinical signs 
and symptoms of heart failure like: 
• 
Exertional dyspnea or Dyspnea at rest 
• 
Orthopnea or Paroxysmal nocturnal dyspnea (PND) 
• 
Acute pulmonary edema  
• 
Fluid retention; or the description of rales, jugular venous 
distension  
• 
Pulmonary edema on physical exam, or pulmonary edema on 
chest x-ray presumed to be cardiac dysfunction 
A low ejection fraction alone, without clinical evidence of heart failure 
does not qualify as heart failure. 
An elevated BNP without other supporting documentation should not 
be reported as CHF 
STS 

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Term 
Definition 
Reference/ 
Justification 
Coronary 
Obstruction 
Angiographic or echocardiographic evidence of a new, partial or 
complete, obstruction of a coronary artery lumen or ostium, either by 
the valve prosthesis itself, the native leaflets, calcifications, or 
dissection, occurring during or after the TAVR procedure. 
Mechanical coronary artery obstruction following TAVR includes: 
• 
impingement of the coronary ostia by the valve support structure 
in the setting of suboptimal valve positioning and/or ‘small aortic 
root’ anatomy; OR 
• 
displacement of native aortic valve leaflets towards the coronary 
ostia during TAVR 
VARC-2/ 
STS/ 
Sponsor 
Device 
For the determination of device relationship, the study device 
consists of: 
• 
Edwards CENTERA THV 
• 
Edwards CENTERA Delivery System 
• 
Edwards eSheath Introducer Kit 
• 
Edwards Dilator Kit 
Sponsor 
Device 
(Valve) 
Fracture 
The separation of any portion of the frame into two or more parts; as 
may be determined by radiography, computed tomography (CT), 
magnetic resonance imaging (MRI) or by direct examination. 
Sponsor 
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.  The intended 
performance of a device refers to the intended use for which the 
device is labeled. 
FDA, 21 CFR 
803.3(m) 
Device 
(Valve) 
Thrombosis 
Any thrombus attached to or near an implanted valve that is an 
incidental imaging finding (echocardiography or CT etc.) and is 
asymptomatic, occludes part of the blood flow path, interferes with 
valve function (immobility of one or more leaflets etc.), or is 
sufficiently large to warrant treatment. 
Prosthetic valve-associated thrombus identified at autopsy in a 
patient whose cause of death was not valve-related should not be 
reported as valve thrombosis 
VARC-2 
Endocarditis 
Endocarditis must meet at least one of the following: 
• 
Fulfilment of the Duke endocarditis 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 
37 
EuroSCORE 
II 
http://www.euroscore.org/calc.html  
European 
System for 
Cardiac 
Operative 
Risk 
Evaluation 
Explant 
Removal of the investigational valve implant regardless of reason 
after the Index procedure is complete. 
Sponsor 

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Term 
Definition 
Reference/ 
Justification 
Hemolysis 
The presence of a paravalvular leak on transesophageal or 
transthoracic echocardiography plus anemia requiring transfusion 
plus acute decrease in haptoglobin levels and/or increase in Serum 
Lactate Dehydrogenase (LDH) levels and/or standard blood 
examinations supporting hemolysis (Complete Blood Count, 
Peripheral Smear, etc.) and diagnosis of hemolysis due to prosthetic 
valve confirmed by a hematologist. 
Sponsor 
Hospitalizatio
n (repeat) 
Repeat hospitalization is defined as admission to an inpatient unit or 
ward in the hospital or emergency department stay for ≥24 hours, for 
either diagnostic or therapeutic purpose. 
Hospitalization for the valve implant procedure (Index procedure) is 
not considered repeat hospitalization. 
Hospitalizations planned for pre-existing conditions are excluded 
unless there is worsening of the baseline condition. 
Sponsor 
Hospitalizatio
n (Valve-
related or 
Cardiovascula
r) 
Prosthetic Aortic Valve-related rehospitalization is repeat 
hospitalization for symptoms of prosthetic valve related 
decompensation due to an acute, subacute, or late valve prosthesis 
dysfunction such as valve stenosis, valve regurgitation, valve 
thrombosis, endocarditis or bleeding complications related to oral 
anticoagulation or antiplatelet therapy for valve-related 
thromboembolic event prevention. 
This diagnosis also requires these symptoms of valve disease not 
related to other diagnoses like: 
• 
documentation of anginal symptoms with no clinical evidence that 
angina was related to CAD or ACS 
• 
documented loss of consciousness which is not related to seizure 
or tachyarrhythmia 
 
Valve Procedure-related rehospitalization is repeat hospitalization 
for complications related to the index valve procedure such as 
bleeding and vascular complications, stroke/TIA, arrhythmias and 
AKI.  This does not include complications indirectly related to the 
procedure or related to the hospitalization such as UTI, dehydration, 
other hospital acquired infections, etc. 
 
Heart failure related hospitalization is defined as repeat 
hospitalization for clinical symptoms, objective signs and/or 
diagnostic evidence of worsening heart failure and necessitating a 
medical intervention like administration of intravenous (Ex: IV 
diuretics, Vasopressors etc.) or mechanical heart failure 
therapies(Ex: Intra-aortic balloon pump, Left ventricular assist 
devices and TAVR valve reintervention etc.). 
 

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Term 
Definition 
Reference/ 
Justification 
Hypertension 
Hypertension is defined as a systolic blood pressure (SBP) of 140 
mmHg or more, or a diastolic blood pressure (DBP) of 90 mmHg or 
more or taking antihypertensive medication. 
Joint National 
Committee 
on 
Prevention, 
Detection, 
Evaluation, 
and 
Treatment of 
High Blood 
Pressure 
(JNC 7) 
Hypertrophic 
Cardiomyopat
hy (HOCM) 
Cardiomyopathy is a term applied to a wide spectrum of cardiac 
diseases in which the predominant feature is poor myocardial 
function in the absence of any anatomic abnormalities. 
Idiopathic hypertrophic subaortic stenosis (IHSS) is also known as 
hypertrophic obstructive cardiomyopathy (HOCM) and is 
characterized by a primary hypertrophy of the myocardium.  The 
obstructive forms involve different degrees of dynamic subvalvar 
aortic obstruction from a thickened ventricular wall and anterior 
motion of the mitral valve. 
Cardiomyopathies are into three entities: 
1. Dilated, characterized by ventricular dilatation and systolic 
dysfunction 
2. Hypertrophic, characterized by physiologically inappropriate 
hypertrophy of the left ventricle 
3. Restrictive, characterized by diastolic dysfunction, with a 
presentation often identical to constrictive pericarditis. 
STS 
Congenital 
Heart 
Surgery 
Database 
Data 
Specification
s 
Hypotension 
Hypotension is defined as a systolic blood pressure (SBP) lower than 
90 mmHg, or mean arterial pressure (MAP) lower than 60 mmHg 
Sponsor 
Index 
Hospitalizatio
n (Index 
Procedure 
Hospitalizatio
n) 
Index hospitalization is defined as the period of in-hospital stay for 
the prosthetic valve implant procedure.  The period of Index 
hospitalization begins with date and time of admission for valve 
implant procedure and continues till the date and time the patient is 
discharged from the hospital where Index procedure is done. 
Sponsor 
Lung Disease, 
Severe 
FEV1 < 50% predicted or currently on home oxygen 
Sponsor 
Mini-Mental 
State 
Examination 
(MMSE) 
A questionnaire that is used extensively in clinical and research 
settings to measure cognitive impairment. 
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Term 
Definition 
Reference/ 
Justification 
Modified 
Rankin Scale 
(mRS) 
A commonly used scale for measuring the degree of disability or 
dependence in the daily activities of people who have suffered a 
stroke, as follows: 
0 No symptoms at all 
1 No significant disability despite symptoms; able to carry out all 
usual duties and activities 
2 Slight disability; unable to carry out all previous activities, but able 
to look after own affairs without assistance 
3 Moderate disability; requiring some help, but able to walk without 
assistance 
4 Moderately severe disability; unable to walk without assistance 
and unable to attend to own bodily needs without assistance 
5 Severe disability; bedridden, incontinent and requiring constant 
nursing care and attention 
6 Dead 
39 
Mortality, All-
Cause 
Cardiovascular mortality 
Any of the following criteria: 
• 
Death due to proximate cardiac cause (e.g. myocardial infarction, 
cardiac tamponade, worsening heart failure) 
• 
Death caused by non-coronary vascular conditions such as 
neurological events, pulmonary embolism, ruptured aortic 
aneurysm, dissecting 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 deaths including structural or nonstructural valve 
dysfunction or other valve-related adverse events 
• 
Sudden or unwitnessed death 
• 
Death of unknown cause 
Non-cardiovascular mortality 
Any death in which the primary cause of death is clearly related to 
another condition (e.g. trauma, cancer, suicide). 
VARC-2 

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Term 
Definition 
Reference/ 
Justification 
Myocardial 
Infarction 
An acute ischemic event that is associated with documented and 
clinically significant myocardial necrosis  
Any one of the following criteria meets the diagnosis for MI: 
 
Periprocedural MI (≤ 72H after Index procedure)  
New signs or symptoms of ischemia. 
• 
Symptoms like chest pain or shortness of breath; 
• 
Ischemic signs like ECG changes indicative of new ischemia 
[new ST segment elevation/depression of ≥1mm in ≥2 contiguous 
leads or new persistent left bundle branch block (LBBB)] or 
• 
New pathological Q-waves in ≥2 contiguous leads or 
• 
Imaging evidence of a new loss of viable myocardium or new wall 
motion abnormality 
• 
AND Elevated cardiac biomarkers (Peak CK-MB rises post-
procedure exceeding 5× the upper reference limit for CK-MB OR 
Peak troponin rises post-procedure exceeding 15× as the upper 
reference limit for troponin) 
• 
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. 
STS 
 
Spontaneous MI (Before Index Procedure or > 72 hours after the 
index procedure) 
Detection of rise and/or fall of cardiac biomarkers (preferably 
Troponin) with at least one value above the 99th percentile URL 
together with at least one of the following: 
• 
Symptoms of ischemia like chest pain or shortness of breath; 
• 
ECG changes indicative of new ischemia (new ST-segment or T-
wave changes or new LBBB) or new pathologic Q-waves in ≥ 2 
contiguous leads 
• 
Imaging evidence of a new loss of viable myocardium or new wall 
motion abnormality 
MI associated with sudden, unexpected cardiac death 
Sudden cardiac death or cardiac arrest, often with symptoms 
suggestive of myocardial ischemia, accompanied by presumably new 
ST-segment 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 
 
Pathologic findings of an acute myocardial infarction 
National 
Institutes of 
Health Stroke 
Scale 
(NIHSS) 
The NIHSS is a method/tool developed by the National Institutes of 
Health used to gauge the severity of a stroke.  NIHSS is a tool to help 
physicians objectively determine the severity of a stroke, help predict 
clinical outcomes and help guide management. 
NIHSS/Spon
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Term 
Definition 
Reference/ 
Justification 
New York 
Heart 
Association 
Classification 
(NYHA) 
NYHA 
Class 
Functional Capacity 
I 
Patients with cardiac disease but without resulting limitation of 
physical activity.  Ordinary physical activity does not cause undue 
fatigue, palpitation, dyspnea or anginal pain. 
II 
Patients with cardiac disease resulting in slight limitation of 
physical activity.  They are comfortable at rest.  Ordinary physical 
activity results in fatigue, palpitation, dyspnea or anginal pain. 
III 
Patients with cardiac disease resulting in marked limitation of 
physical activity.  They are comfortable at rest.  Less than 
ordinary activity causes fatigue, palpitation, dyspnea or anginal 
pain. 
IV 
Patients with cardiac disease resulting in inability to carry on any 
physical activity without discomfort.  Symptoms of heart failure or 
the anginal syndrome may be present even at rest.  If any 
physical activity is undertaken, discomfort is increased. 
40 
Paravalvular 
Leak (PVL) 
Paravalvular or paraprosthetic leak is a complication associated with 
the implantation of a prosthetic heart valve whether traditional 
(surgical) or a transcatheter (TAVR) approach. 
PVL refers to blood flowing through a channel between the structure 
of the implanted valve and cardiac tissue as a result of a lack of 
appropriate sealing 
ESC 
Peripheral 
Vascular 
Disease 
(PVD) 
Includes peripheral arterial disease of upper and lower extremity, 
renal, mesenteric, and abdominal aortic systems, as follows: 
• 
Claudication, either with exertion or at rest 
• 
Amputation for arterial vascular insufficiency 
• 
Vascular reconstruction, bypass surgery, or percutaneous 
intervention to the extremities (excluding dialysis fistulas and vein 
stripping) 
• 
Documented abdominal aortic aneurysm with or without repair 
• 
Positive noninvasive test (e.g., ankle brachial index =< 0.9, 
ultrasound, magnetic resonance or computed tomography 
imaging of > 50% diameter stenosis in any peripheral artery, i.e., 
renal, subclavian, femoral, iliac) or angiographic imaging 
Peripheral arterial disease excludes disease in the carotid, 
cerebrovascular arteries or thoracic aorta. 
PVD does not include DVT. 
STS 
Pulmonary 
Hypertension 
Pulmonary hypertension (PH), defined as a mean pulmonary arterial 
pressure ≥ 25 mmHg at rest in the presence of Left Atrial 
Pressure(LAP)/Wedge pressure ≤15 mmHg and is often 
characterized by a progressive and sustained increase in pulmonary 
vascular resistance that eventually may lead to right ventricular (RV) 
failure 
ACC/Sponso
r 
Pre-existing 
Condition 
A pre-existing condition is any chronic, recurring condition identified 
prior to enrollment in a clinical study, whether present at enrollment 
or not.  A preexisting condition is not an adverse event unless it 
worsens as a result of the study treatment. 
Sponsor 

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Term 
Definition 
Reference/ 
Justification 
Reintervention 
Any intervention that repairs, alters or replaces a previously 
implanted or operated valve, which occurs after the completion of 
the valve implant procedure and the transfer to the procedure room.  
These interventions include: 
• 
Balloon aortic valvuloplasty 
• 
Surgical aortic valve replacement 
• 
Valve in valve 
• 
Paravalvular leak closure 
STS/AATS 
Serious 
Adverse 
Event (SAE) 
Adverse Event that: 
• 
Led to death, 
• 
Led to serious deterioration in the health of the subject, that 
either resulted in 
o 
a life-threatening illness or injury, or 
o 
a permanent impairment of a body structure or a body 
function, or 
o 
in-patient or prolonged hospitalization, or 
o 
medical or surgical intervention to prevent life-threatening 
illness or injury or permanent impairment to a body structure 
or a body function, 
• 
Led to fetal distress, fetal death or a congenital abnormality or 
birth defect 
• 
Significant medical event: 
Important medical events that do not meet the above criteria may 
still be considered an SAE if they seriously jeopardize the subject 
and require immediate medical or surgical intervention to prevent 
one of the aforementioned outcomes. 
ISO 14155-
1:2011 
FDA (21 CFR 
312.32 (a) 
Stroke / 
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, or other 
neurological signs or symptoms consistent with stroke 
AND 
No other readily identifiable nonstroke 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 
VARC-2 

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Term 
Definition 
Reference/ 
Justification 
Confirmation of the diagnosis by at least one of the following#: 
• 
Neurology or neurosurgical specialist 
• 
Neuroimaging procedure (MR or CT scan) 
• 
Clinical presentation alone 
 
Neurological event type classification: 
Stroke: duration of a focal or global neurological deficit ≥24 h OR 
<24 h if available neuroimaging documents a new intracranial or 
subarachnoid hemorrhage (hemorrhagic stroke) or central nervous 
system infarction (ischemic stroke) OR the neurological deficit results 
in death. 
TIA: duration of a focal or global neurological deficit <24 h and 
neuroimaging does not demonstrate a new hemorrhage or infarct 
 
Stroke etiological classification: 
1. Hemorrhagic: an acute episode of focal or global cerebral or 
spinal dysfunction caused by intraparenchymal, intraventricular, or 
subarachnoid hemorrhage. 
2. Ischemic: an acute episode of focal cerebral, spinal, or retinal 
dysfunction caused by an infarction of the central nervous system 
tissue 
3. Undetermined: stroke with insufficient information to allow 
categorization as ischemic or hemorrhagic. 
 
Stroke severity classification: 
1. Non-disabling: a mRS score of <2 at 90 days or the last available 
clinical visit with evaluable data or one that does not result in an 
increase of at least one mRS category from an individual’s pre-stroke 
baseline 
2. Disabling: a mRS score of ≥2 at 90 days or the last available 
clinical visit with evaluable data and an increase of at least one mRS 
category from an individual’s pre-stroke baseline 
Structural 
Valvular 
Deterioration 
(SVD) 
Structural deterioration includes dysfunction or deterioration due to 
changes intrinsic to the valve, such as wear, fracture, calcification, 
leaflet tear, leaflet retraction, suture line disruption of components, 
prosthetic valve thickening, stenosis as determined by reoperation, 
autopsy or clinical investigation 
SVD excludes infection/endocarditis or thrombosis 
41 
STS Adult 
Cardiac 
Surgery Risk 
Calculator 
The Society of Thoracic Surgeons’ risk models predict the risk of 
operative mortality and morbidity after adult cardiac surgery on the 
basis of subject demographic and clinical variables. 
http://riskcalc.sts.org/stswebriskcalc/#/  
STS 
Syncope 
A fainting spell or loss of consciousness 
STS 
SYNTAX 
Score 
An angiographic grading tool to determine the complexity of CAD. 
http://www.syntaxscore.com/ 
http://ir-nwr.ru/calculators/syntaxscore/frameset.htm 
 
TAVR Risk 
Score 
http://tools.acc.org/TAVRRisk/#!/content/evaluate/ 
 

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Term 
Definition 
Reference/ 
Justification 
THV-in-THV 
An additional valve prosthesis is implanted within a previously 
implanted prosthesis because of suboptimal device position and/or 
function, during or after the valve implant procedure 
VARC-2 
Transient 
Ischemic 
Attack (TIA) 
See “Stroke / Transient Ischemic Attack (TIA)” 
 
Unanticipated 
Adverse 
Device Effect 
(UADE) 
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. 
FDA 
Valve Implant 
Procedure 
Placement of study device and/or additional procedures occurring in 
the procedure room which are completed prior to subject transfer to a 
post-procedure recovery unit (e.g. Recovery Room, ICU/CCU, etc. 
The valve implant procedure will be considered to have started when 
the first interventional access-related puncture (arterial) is 
established.  The end of valve implant procedure is defined as date 
and time of vascular closure post-eSheath removal. 
Performance of TEE does not by itself constitute start of procedure 
Sponsor 
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 
Vascular 
Injury 
Injury to the vascular system that may be caused by the implanted 
valve or other accessories like guidewires, vascular sheaths, delivery 
catheters, or any balloons used for implanted valve dilatation etc.  
This includes arterial injuries like dissection, perforation, 
arteriovenous fistula, pseudoaneurysm formation, retroperitoneal 
hemorrhage, thromboembolism or incomplete arteriotomy closure 
and venous injuries like perforation, tears, or venous thrombosis 
including pulmonary embolism etc. and cardiac structural injuries like 
perforation or tearing of the major cardiac structures, 
pseudoaneurysm, cardiac tamponade or atrial septal defect etc. 
VARC-2 / 
Sponsor 
 
 
 

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