ProspeCtive, nOn-randoMized, MulticENter Clinical Evaluation of Edwards Pericardial Aortic and Mitral Bioprostheses (Models 11000A and 11000M) With a New Tissue Treatment Platform (COMMENCE)
Phase: NA
Conditions: Aortic Stenosis, Mitral Stenosis, Aortic Valve Insufficiency, Mitral Valve Insufficiency, Heart Failure
Sponsor: Edwards Lifesciences

 
 
 
 
CLINICAL INVESTIGATIONAL PLAN 
 
ProspeCtive, nOn-randoMized, MulticENter Clinical evaluation 
of the Edwards Pericardial Aortic & Mitral Bioprostheses 
(Models 11000A & 11000M) with a new tissue treatment 
platform (COMMENCE #2012-02)  
 
 
  
NCT01757665 
 
March 03, 2021 
 

 
 
 
CONFIDENTIAL AND PROPRIETATARY DATA: This document and the information contained herein may not be reproduced, used, or disclosed 
without written permission from Edwards Lifesciences LLC 
Revision J: 03 March 2021 
 
 
Page 1 of 43 
                                                    
Protocol Number 2012-02 
 
 
 
CLINICAL INVESTIGATIONAL PLAN 
Revision J 
03 March 2021 
 
 
 
 
ProspeCtive, nOn-randoMized, MulticENter Clinical evaluation 
of the Edwards Pericardial Aortic & Mitral Bioprostheses 
(Models 11000A & 11000M) with a new tissue treatment 
platform (COMMENCE TRIAL) 
 
Trial Sponsor: 
Edwards Lifesciences LLC 
One Edwards Lifesciences Way 
Irvine, CA 92614 USA 
 
 
Edwards Lifesciences, the stylized E logo, Carpentier-Edwards, Magna Ease, PERIMOUNT, PERIMOUNT Magna, and 
ThermaFix are trademarks of Edwards Lifesciences Corporation 
 
 
 

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PAGE 2 OF 47 
 
 
1.0  INVESTIGATOR SIGNATURE PAGE 
Trial Title: 
ProspeCtive, nOn-randoMized, MulticENter Clinical evaluation of 
the Edwards Pericardial Aortic & Mitral Bioprostheses(Models 
11000A and 11000M) with a new tissue treatment platform 
(COMMENCE TRIAL) 
Protocol Number: 
2012-02 
Version Number: 
Rev. J 
Date: 
03 March 2021 
I have read this protocol and agree to participate in the clinical investigation of the Model 11000A and 
Model 11000M sponsored by Edwards Lifesciences LLC.  I agree to conduct this investigation according to 
the requirements of the trial protocol and in accordance with Good Clinical Practice, applicable State and 
U.S. Federal regulations and conditions imposed by the reviewing Institutional Review Board/Ethics 
Committee/Research Ethics Board.  I agree to supervise all sub-investigators at my site as well as the use 
of all of the investigational devices at my institution and to ensure appropriate informed consent is 
obtained from all subjects prior to inclusion in this trial.   
 
 
 
INVESTIGATOR NAME 
 
INVESTIGATOR TITLE 
INVESTIGATOR SIGNATURE 
 
DATE 
 
 
 
 
 
 
 

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3.0  PROTOCOL SYNOPSIS 
Title: 
ProspeCtive, nOn-randoMized, MulticENter Clinical evaluation of the Edwards 
Pericardial Aortic & Mitral Bioprostheses(Models 11000A and 11000M) with a 
new tissue treatment platform (COMMENCE TRIAL) 
Protocol Number 
2012-02 
Trial Sponsor: 
Edwards Lifesciences 
One Edwards Way  
Irvine, CA 92614 
  
 
 
 
Trial Device: 
Edwards Pericardial Aortic Bioprosthesis, Model 11000A 
Edwards Pericardial Mitral Bioprosthesis, Model 11000M 
Indication for Use: 
The Edwards Pericardial Aortic Bioprosthesis, Model 11000A, is indicated for 
patients who require replacement of their native or prosthetic aortic valve. 
The Edwards Pericardial Mitral Bioprosthesis, Model 11000M, is indicated for 
patients who require replacement of their native or prosthetic mitral valve. 
Trial Objective: 
The objective of this trial is to confirm that the modifications to tissue 
processing, valve sterilization, and packaging of the FDA-approved 
(P860057/S042) Carpentier-Edwards PERIMOUNT Magna Ease Pericardial Aortic 
Bioprosthesis, Model 3300TFX, which will be designated as the Edwards 
Pericardial Aortic Bioprosthesis Model 11000A, and the Carpentier-Edwards 
PERIMOUNT Magna Mitral Ease Pericardial Bioprosthesis, Model 7300TFX, 
which will be designated as the Edwards Pericardial Mitral Bioprosthesis Model 
11000M do not raise any new questions of safety and effectiveness in subjects 
who require replacement of their native or prosthetic aortic or mitral valve. The 
only differences between the Model 3300TFX and the Model 11000A and 
between the Model 7300TFX and the Model 11000M are modifications in tissue 
processing, valve sterilization, and packaging.   
Trial Design: 
Multicenter, prospective, double arm trial – Up to seven hundred (700) aortic 
valve replacement (AVR) subjects and up to one hundred seventy five (175) 
mitral valve replacement (MVR) subjects at up to forty (40) clinical sites will be 
enrolled.  An enrollment rate of three (3) to four (4) subjects per site per month 
is anticipated. At least eight (8) centers will implant and follow for at least 1 year, 

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PAGE 5 OF 47 
 
thirty (30) or more AVR or thirty (30) or more AVR/MVR subjects. Analysis for 
the aortic arm will be performed when at least three hundred (300) AVR subjects 
have completed the POD 390 follow-up visit and at least eight hundred (800) 
AVR patient-years of cumulative follow-up have been reached. Analysis for the 
mitral arm will be completed when at least three hundred (300) combined aortic 
and mitral subjects have completed the POD 390 follow-up visit and at least 
eight hundred (800) AVR and at least one hundred (100) MVR patient-years of 
cumulative follow-up have been reached. The tests for the trial endpoints were 
performed and the trial data was submitted to FDA for the PMA approval of the 
devices evaluated under the aortic and mitral arms. All IDE Subjects (aortic and 
mitral arms) who are currently enrolled and alive will be followed to 5 years. In 
an effort to obtain sufficient long-term data, approximately 250 Subjects 
implanted with the Model 11000A valve at up to 10 sites will be asked to consent 
for extended follow-up annually through 10 years post-procedure.  In addition, 
approximately 25 Subjects implanted with the Model 11000M valve at select 
sites will be asked to consent for extended follow-up annually through 10 years 
post procedure.  
Trial Sites: 
Participating sites are chosen based on their experience in conducting clinical 
trials, their surgical experience implanting bioprosthetic valves, as well as their 
ability to maintain robust subject enrollment and follow-up. The investigational 
sites will be selected throughout the United States, Canada, Europe and Asia 
Pacific.  
Trial Duration: 
Total enrollment period for this trial is estimated to be 1095 days or 3 years.  
Subject duration in the trial is estimated to be no longer than 1825 days (5 years) 
or 3650 days (10 years) for those who have consented to continued follow-up.  
Overall duration of the trial is estimated to be 3833 days or 10.5 years, and will 
involve at least 800 AVR patient-years and at least 100 MVR patient-years of 
cumulative follow-up. The trial begins with the enrollment of the first subject 
and ends after the last subject is exited from the trial after completing the last 
follow-up visit at approximately postoperative day (POD) 3650, all subjects are 
fully monitored, all outstanding data queries are resolved and all trial sites are 
closed to follow-up. 
 
Visit 
Visit Window (Days) 
Timing from Implant (Day 0) 
Screening/Baseline 
 
Day -60 to Day 0 

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Trial Follow-Up 
Visits: 
Discharge1 
 
Prior to Discharge 
POD 30 
-5/+10 
Day 25 to 40  
POD 105 
- 15/+30 
Day 90 to 135 
POD 390 (1 yr) 
-25/+45 
Day 365 to 435 
POD 730 (2 yr) 
-25/+45 
Day 705 to 775 
POD 1095 (3 yr) 
-25/+45 
Day 1070 to 1140 
POD 1460 (4 yr) 
-25/+45 
Day 1435 to 1505 
POD 1825 (5 yr) 
-25/+45 
Day 1800 to 1870 
POD 2190 (6 yr)* 
-55/+75 
Day 2135 to 2265  
POD 2555 (7 yr)* 
-55/+75 
Day 2500 to 2630 
POD 2920 (8 yr)* 
-55/+75 
Day 2865 to 2995 
POD 3285 (9 yr)* 
-55/+75 
Day 3230 to 3360 
POD 3650 (10yr)* 
-55/+75 
Day 3595 to 3725 
 
1 Subjects who are not discharged within 10 days post procedure must have an echocardiogram 
to assess performance of the trial valve. Those subjects will not require an additional 
echocardiogram at discharge. 
*Subjects who have consented to continued follow up with the Model 11000A or Model 11000M 
valve. 
Trial Endpoints:  
Primary Safety Endpoint (up to 390 days post-implant): 
The primary safety endpoint for the trial is the rate of implanted subjects that 
experience structural deterioration of the trial valve by the time of the POD 390 
follow-up visit. The null hypothesis is that the rate of structural valve 
deterioration at one year is greater than 1%. The alternative hypothesis is that 
this rate is less than 1%.  
Primary Safety Endpoint (Continued follow-up): 
For continued follow-up of Subjects, the primary safety endpoint for the trial is 
the rate of implanted subjects that experience structural deterioration of the 
trial valve as determined by a Clinical Events Committee (CEC). 
Secondary Safety Endpoints (Pre-approval):  
Safety is established by comparing the occurrence of specific safety endpoints 
to the objective performance criteria (OPC) reported in Table R.1 in ISO 
5840:2009, Annex R.1 as recommended by the FDA in the Draft Guidance 
involving Heart Valves – Investigational Device Exemption (IDE) and Premarket 
Approval (PMA) Applications (2010). 
 
Secondary Safety Endpoints (Continued follow-up):  

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For continued follow-up of Subjects, linearized rates will be used to summarize 
the following safety endpoints for the late (>30 days) post-operative period. 
 
 
• 
Thromboembolism 
• 
Valve thrombosis 
• 
All bleeding/hemorrhage 
• 
Major bleeding/hemorrhage 
• 
All paravalvular leak  
• 
Major paravalvular leak  
• 
Non-structural valve deterioration 
 
• 
Endocarditis 
• 
All-cause mortality 
• 
Trial valve-related mortality 
• 
Trial valve-related reoperation 
• 
Explant  
• 
Hemolysis 
 
Effectiveness Endpoints: 
• 
Clinically acceptable hemodynamic performance confirmed by core lab 
evaluation of echocardiography 
• 
New York Heart Association (NYHA) functional class compared to baseline 
• 
Change in Quality of Life questionnaire Short Form 12 version 2 (SF-12v2) 
from baseline/screening to POD 390 
 
Additional Data in support of analysis: 
• 
Blood Data 
Subject Enrollment: 
Inclusion Criteria: 
Each subject is required to meet all of the following inclusion criteria: 
1. Is 18 years or older 
2. Provides written informed consent prior to trial procedures 
3. Agrees to attend all follow-up assessments for up to 5 years and is willing to 
comply with specified follow-up evaluations at clinical investigational sites 
that are participating in the COMMENCE trial and/or obtain the protocol-
specified diagnostic tests at centers that are under the same IRB or the same 
healthcare system 
4. Diagnosed with aortic or mitral valve disease requiring valve replacement 
based on pre- operative evaluation  
5.  Scheduled to undergo planned aortic or mitral valve replacement with or 
without concomitant bypass surgery 
6.  Scheduled to undergo planned aortic valve replacement with or without 
resection and replacement of the ascending aorta from the sinotubular 
junction and without the need for circulatory arrest for hemi arch or arch 
replacement 
 
 
 

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PAGE 8 OF 47 
 
 
Exclusion criteria: A subject meeting any of the following criteria shall be excluded: 
1. Requires emergency surgery 
2. Requires planned multiple valve replacement/ repair (with the exception of 
mitral valve replacement with tricuspid valve repair) 
3. Has prior valve surgery, which included implant of a bioprosthetic valve, 
mechanical valve, or annuloplasty ring that will remain in situ  
4. Requires a surgical procedure outside of the cardiac area (e.g. vascular 
bypass) 
5. Requires surgical replacement of the aortic root 
6. Has active endocarditis/myocarditis or endocarditis/myocarditis within 3 
months to the scheduled aortic or mitral valve replacement surgery 
7. Has renal insufficiency as determined by creatinine (S-Cr) level ≥ 2.5 mg/dL 
or end-stage renal disease requiring chronic dialysis at screening visit  
8. Has MRI or CT scan confirmed stroke, cerebrovascular accident (CVA) or 
transient ischemic attack (TIA) within 6 months (180 days) prior to planned 
valve surgery  
9. Has acute myocardial infarction (MI) within 30 days prior to planned valve 
surgery  
10. Has presence of non-cardiac disease limiting life expectancy to less than 12 
months 
11. Diagnosed with hypertrophic obstructive cardiomyopathy (HOCM) 
12. Diagnosed with abnormal calcium metabolism and hyperparathyroidism 
13. Exhibits left ventricular ejection fraction  ≤ 20% as validated by diagnostic 
procedure prior to planned valve surgery 
14. Echocardiographic evidence of an intra-cardiac mass, thrombus, or 
vegetation 
15. Hemodynamic or respiratory instability requiring inotropic support, 
mechanical circulatory support, or mechanical ventilation within 30 days 
prior to planned valve surgery 
16. Documented leukopenia (WBC < 3.5x 103/µL), acute anemia (Hgb < 10.0 
gm/dL or 6 mmol/L), or thrombocytopenia (platelet count < 50x103/µL) 
accompanied by history of bleeding diathesis or coagulopathy 
17. Has prior organ transplant or is currently an organ transplant candidate 
18. Current or recent participation (within 6 weeks prior to surgery) in another 
drug or device trial  
19. Was previously implanted with trial device (Model 11000A or Model 
11000M)1 
20. Pregnant (female subject of childbearing potential only), lactating or 
planning to become pregnant during the duration of participation in trial 
21. Currently incarcerated or unable to give voluntary informed consent 
22. Documented history of substance (drug or alcohol) abuse within the last 5 
years prior to implant 
23. Requires concomitant left ventricular assist device (LVAD) placement 

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4.0  ABBREVIATIONS 
ACC 
American College of Cardiology 
IRB 
Institutional Review Board 
AE 
Adverse Event 
ISO 
International Standardization Organization 
AHA 
American Heart Association 
LVOT 
Left Ventricular Outflow Tract 
AS 
Aortic Stenosis 
MI 
Myocardial Infarction 
ASD 
Atrial Septal Defect 
MOF 
Multi-system Organ Failure 
AVR 
Aortic Valve Replacement 
MR 
Magnetic Resonance 
CABG 
Coronary Artery Bypass Graft 
MVR 
Mitral Valve Replacement 
CBC 
Complete Blood Count 
NSVD 
Nonstructural Valve Dysfunction 
CEC 
Clinical Events Committee 
NYHA 
New York Heart Association 
CFR 
Code of Federal Regulations 
OPC 
Objective Performance Criteria 
CO/CI 
Cardiac Output/Cardiac Index 
OUS 
Outside United States 
CRF 
Case Report Form 
PFO 
Patent Foramen Ovale 
CV 
Critical Value 
PMA 
Premarket Approval  
CVA 
Cerebrovascular Accident 
PO 
Postoperative 
DIC 
Disseminated Intravascular Coagulation 
POD 
Postoperative Day 
DMC 
Data Monitoring Committee 
PT 
Prothrombin Time 
EC 
Ethics Committee 
PTFE 
Polytetrafluoroethylene 
eCRF 
Electronic Case Report Form 
PTT 
Partial Thromboplastin Time 
ECG 
Electrocardiogram 
PVL 
Paravalvular Leak 
EDC 
Electronic Data Capture 
QOL 
Quality of Life 
EOA 
Effective Orifice Area 
RBC 
Red Blood Cell  
FDA 
Food and Drug Administration 
REB 
Research Ethics Board 
FMEA 
Failure Modes and Effects Analysis 
RGA 
Returned Good Authorization 
GCP 
Good Clinical Practice 
SAE 
Serious Adverse Effect 
GLP 
Good Laboratory Practices 
SAR 
Specific Absorption Rate 
HGB 
Hemoglobin 
SAVR 
Surgical Aortic Valve Replacement 
HIPAA 
Health Insurance Portability & Accountability Act 
SMVR 
Surgical Mitral Valve Replacement 
HCT 
Hematocrit 
SF-12 
Short Form 12 Health Survey 
HIT 
Heparin Induced Thrombocytopenia 
SVD 
Structural Valve Deterioration 
HOCM Hypertrophic Obstructive Cardiomyopathy 
TAD 
Tissue Annulus Diameter 
ICF 
Informed Consent Form 
TEE 
Transesophageal Echocardiography 
ICU 
Intensive Care Unit 
TIA 
Transient Ischemic Attack 
ID 
Identification 
TTE 
Transthoracic Echocardiography 
IDE 
Investigational Device Exemption 
UADE 
Unanticipated Adverse Device Effect 
IE 
Infective Endocarditis 
WBC 
White Blood Cell  
IFU 
Instructions for Use 
 
INR 
International Normalized Ratio 
 
 
 
 
 
 

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Table of Contents 
 
Section 
Page 
1.0 
INVESTIGATOR SIGNATURE PAGE ........................................................................................... 2 
2.0 
TRIAL CONTACT PERSONNEL .................................................................................................. 3 
2.1 SPONSOR CONTACT ......................................................................................................................... 3 
2.2 TRIAL CONTACT ................................................................................................................................ 3 
3.0 
PROTOCOL SYNOPSIS ............................................................................................................. 4 
4.0 
ABBREVIATIONS ..................................................................................................................... 9 
5.0 
TRIAL OVERVIEW ................................................................................................................. 13 
5.1 INTRODUCTION AND BACKGROUND .............................................................................................. 13 
5.2 DEVICE DESCRIPTION ..................................................................................................................... 14 
5.3 REPORT OF PRIOR INVESTIGATIONS .............................................................................................. 16 
6.0 
BENEFITS AND RISKS ............................................................................................................ 17 
6.1 BENEFITS ........................................................................................................................................ 17 
6.2 RISKS .............................................................................................................................................. 18 
6.3 MINIMIZING SUBJECT RISK ............................................................................................................ 19 
7.0 
TRIAL DESIGN ...................................................................................................................... 19 
7.1 OBJECTIVE ...................................................................................................................................... 19 
7.2 DESIGN .......................................................................................................................................... 20 
7.3 ENDPOINTS .................................................................................................................................... 20 
7.4 ADDITIONAL CLINICAL MEASURES ................................................................................................. 22 
7.5 NUMBER OF SUBJECTS ................................................................................................................... 22 
7.6 METHODS OF FOLLOW-UP ............................................................................................................. 23 
8.0 
TRIAL POPULATION .............................................................................................................. 24 
8.1 SUBJECT INCLUSION CRITERIA ........................................................................................................ 24 
8.2 SUBJECT EXCLUSION CRITERIA ....................................................................................................... 24 
8.3 ENROLLED POPULATION ................................................................................................................ 26 
8.4 INDEX VALVE POPULATION ............................................................................................................ 26 
8.5 SUBJECT AND TRIAL DURATION ..................................................................................................... 26 
8.6 SUBJECT TERMINATION OR WITHDRAWAL .................................................................................... 26 
9.0 
STATISTICAL METHODS ........................................................................................................ 27 
9.1 ANALYSIS POPULATION ................................................................................................................. 27 
9.2 SAMPLE SIZE .................................................................................................................................. 27 
9.3 STATISTICAL ANALYSIS ................................................................................................................... 27 

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9.4 ADDITIONAL MEASURES ................................................................................................................ 30 
9.5 POOLABILITY .................................................................................................................................. 31 
9.6 ANALYSIS OF COVARIATES ............................................................................................................. 31 
9.7 MISSING DATA ............................................................................................................................... 31 
9.8 FOLLOW-UP AND COMPLIANCE DATA ............................................................................................ 31 
10.0 
TRIAL PROCEDURES .............................................................................................................. 32 
10.1 SUBJECT SCREENING ...................................................................................................................... 32 
10.2 INFORMED CONSENT ..................................................................................................................... 32 
10.3 BASELINE ASSESSMENT .................................................................................................................. 33 
10.4 VALVE REPLACEMENT PROCEDURE ................................................................................................ 33 
10.5 POST INDEX VALVE IMPLANT ......................................................................................................... 34 
10.6 DISCHARGE .................................................................................................................................... 34 
10.7 POST DISCHARGE FOLLOW-UP ASSESSMENTS ................................................................................ 35 
10.8 MISSED FOLLOW-UP ...................................................................................................................... 36 
10.9 DEVICE REMOVAL OR EXPLANT ...................................................................................................... 37 
11.0 
ADVERSE EVENTS ................................................................................................................. 37 
11.1 REPORTING .................................................................................................................................... 37 
11.2 NOTIFICATION OF UADE AND/OR SERIOUS DEVICE RELATED ADVERSE EFFECTS ........................... 38 
11.3 DEATH AND EXPLANTS ................................................................................................................... 38 
11.4 DATA MONITORING COMMITTEE .................................................................................................. 39 
11.5 CLINICAL EVENTS COMMITTEE ....................................................................................................... 39 
12.0 
TRIAL AND DATA MANAGEMENT ......................................................................................... 40 
12.1 TRIAL CORE LABS ........................................................................................................................... 40 
12.2 DEVICE ACCOUNTABILITY ............................................................................................................... 40 
12.3 PROTOCOL DEVIATIONS ................................................................................................................. 41 
12.4 TRIAL SITE INITIATION AND MONITORING PLAN ............................................................................ 42 
12.5 DOCUMENTATION REQUIREMENTS ............................................................................................... 43 
12.6 DATA COLLECTION ......................................................................................................................... 44 
12.7 DATA AND DOCUMENT RETENTION ............................................................................................... 44 
12.8 TRIAL PROTOCOL AMENDMENTS ................................................................................................... 45 
12.9 TRIAL COMPLETION ....................................................................................................................... 45 
12.10 
FUTURE PLANS ....................................................................................................................... 45 
13.0 
STATEMENTS OF COMPLIANCE, CONFIDENTIALITY AND RESPONSIBILITIES ............................ 45 
13.1 GOOD CLINICAL PRACTICE STATEMENT.......................................................................................... 45 
13.2 REGULATIONS AND GUIDELINES .................................................................................................... 46 

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13.3 INVESTIGATOR RESPONSIBILITIES .................................................................................................. 46 
13.4 SPONSOR RESPONSIBILITIES .......................................................................................................... 46 
14.0 
PUBLICATIONS ..................................................................................................................... 47 
15.0 
REFERENCES ........................................................................................................................ 47 
 
TRIAL PROTOCOL ATTACHMENTS 
ATTACHMENT A: 
CLINICAL TRIAL SCHEME 
ATTACHMENT B: 
INSTRUCTIONS FOR USE 
ATTACHMENT C: 
INFORMED CONSENT FORM TEMPLATE 
ATTACHMENT D: 
CASE REPORT FORMS 
ATTACHMENT E: 
CORE LABORATORY PROCEDURE MANUAL 
ATTACHMENT F: 
SERUM GLYCEROL SAMPLE COLLECTION MANUAL 
ATTACHMENT G: 
QUALITY OF LIFE QUESTIONNAIRE (SF-12 V2) 
ATTACHMENT H: 
ADVERSE EFFECT (CODES & DEFINITIONS) 
ATTACHMENT J: 
RESPONSIBILITIES (INVESTIGATOR & SPONSOR) 
ATTACHMENT K: 
SUBJECT IMPLANT CARD 
ATTACHMENT L: 
PROTOCOL DEVIATION CODES 
ATTACHMENT M: DEVICE DEFICIENCY CODES 
ATTACHMENT N: 
CLINICAL TRIAL AGREEMENT 
ATTACHMENT O:  POWER SIMULATION CODE FOR PRIMARY SAFETY ENDPOINT 

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5.0  TRIAL OVERVIEW 
5.1 
INTRODUCTION AND BACKGROUND 
Valvular heart disease is a life-threatening disease that afflicts millions of people worldwide and leads to 
approximately 250,000 valve repairs and/or replacements each year. The number of subjects requiring 
aortic valve replacement (AVR) is increasing due to prolonged life expectancy. Many subjects are 
asymptomatic until the disease is well advanced and, once diagnosed, have poor prognosis depending on 
the severity of valve calcification and history of cardiac events1.  Diseased heart valves can be treated by 
medication, surgical repair or surgical replacement.  
5.1.1 
AORTIC AND MITRAL HEART DISEASE 
Aortic valvular heart disease includes conditions involving any of the following – obstructions of the aortic 
heart valve or stenosis; leakage of the aortic valve, known as regurgitation, incompetence, or insufficiency, 
and combinations of the two, sometimes referred to as mixed disease or combined lesions. Valvular heart 
disease may be caused by any number of factors, including congenital abnormalities, infection by various 
micro-organisms, degenerative calcification and rheumatic heart disease. When subjects become 
symptomatic, angina, syncope, and congestive heart failure (CHF) are the primary clinical signs observed. 
Studies report that among symptomatic subjects with medically treated moderate-to-severe AS, mortality 
rates after the onset of symptoms are approximately 25% at one year and 50% at two years. Other studies 
show that subjects with symptomatic AS have a life expectancy of 2 – 4 years.2 Neither aortic stenosis nor 
aortic insufficiency can be effectively treated medically; however, the symptoms of aortic valve disease 
can be managed medically. 
Stenosis of the mitral valve is the narrowing of the valve opening that causes lower blood flow through 
the valve.  In over 99% of stenotic mitral valves, the etiology is rheumatic disease.3 Other rare causes of 
mitral stenosis include congenital malformed valves, active infective endocarditis, massive annular 
calcium, and metabolic or enzymatic abnormalities.3 Regurgitation of the mitral valve occurs when blood 
flows back into the valve as the leaflets close or leaks through the leaflets after they are closed.  Mitral 
regurgitation has multiple etiologies including: floppy mitral valves, active or healed infective 
endocarditis, papillary muscle dysfunction, annular calcium, idiopathic chordae tendineae rupture, 
rheumatic disease, dilated and hypertrophic cardiomyopathies, endocardial fibrosis, and collagen-
vascular disorders (lupus, scleroderma), or Marfan’s or Marfan-like disorders. Edward et al reviewed data 
collected from 1648 patients between January 1990 and December 1999 in northern New England, and 
noted that mitral valve replacements and repair procedures have substantially increased and indications 
for these procedures have expanded to also include older and sicker patients with less rheumatic and 
more degenerative and coronary artery-related mitral valve problems.4  As the incidence of rheumatic 
mitral stenosis and regurgitation has decreased, mitral regurgitation caused by degenerative disease of 

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the mitral apparatus and caused by the left ventricular dysfunction associated with coronary artery 
disease has become the predominant hemodynamic lesion of the mitral valve.5  
5.1.2 
TREATMENT OF AORTIC AND MITRAL VALVULAR HEART DISEASE 
Aortic stenosis and insufficiency can be treated by surgical intervention, including balloon valvuloplasty, 
valve repair, and valve replacement.  Balloon valvuloplasty, a treatment option for aortic stenosis, utilizes 
a balloon-tipped catheter to stretch open the narrowed valve. Valvuloplasty is predominately used to 
treat children or adults who are poor surgical candidates. Valve repair techniques include annuloplasty 
for dilated valve disease, patching leaflet perforations, resected vegetations, or tears, and leaflet 
extension.6,7  Aortic valve repair for stenosis does not show good clinical results.8  Replacement of the 
aortic valve is indicated for symptomatic subjects and asymptomatic subjects with left ventricular 
dysfunction.  
Diseased mitral valves can be treated by medication, surgical repair and surgical replacement.  Repairing 
the native valve is generally preferred over replacing it.  Surgical repair can involve modifying the valve 
tissue or underlying structures.  This procedure can be performed with or without implantation of an 
annuloplasty ring that provides support to the native valve so that it closes completely and functions 
normally.  If the native valve cannot be repaired, it is replaced by either a mechanical valve (constructed 
from synthetic material) or a tissue bioprosthetic valve (made primarily from animal tissue including 
bovine pericardium, or human valves from cadavers. 
5.1.3 
BIOPROSTHETIC HEART VALVES 
Bioprosthetic heart valves are indicated for use in subjects suffering from valvular heart disease. These 
tissue valves are used particularly in those subjects for whom long-term anticoagulation therapy is 
contraindicated or who may be difficult to maintain on anticoagulation therapy. 
5.2 
DEVICE DESCRIPTION 
Edwards Pericardial Aortic Bioprosthesis 
The Edwards Pericardial Aortic Bioprosthesis, Model 11000A (also referred to as the Model 11000A) is a 
bioprosthesis comprised of bovine pericardium. It is based on the same design as the Carpentier-Edwards 
PERIMOUNT Magna Ease Pericardial Aortic Bioprosthesis, Model 3300TFX, which was approved under 
P860057/S042 on 07 May 2009.  
The physical structure and design of the Model 11000A is identical to the Model 3300TFX, except for tissue 
processing, sterilization and packaging. The Edwards Pericardial Aortic Bioprosthesis, Model 11000A, is a 
trileaflet bioprosthesis comprised of treated bovine pericardium that is mounted on a flexible frame. It is 
available in sizes 19, 21, 23, 25, 27, and 29 mm.  The bioprosthesis is stored in non-aqueous packaging, 
and does not require rinsing prior to implantation. 

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The wireform is made of a cobalt-chromium alloy and is covered with a woven polyester fabric. A cobalt-
chromium alloy/polyester film laminate band surrounds the base of the wireform frame. A silicone sewing 
ring that is covered with a porous polytetrafluoroethylene (PTFE) cloth is attached to the wireform frame. 
The sewing ring has three, equally spaced black silk suture markers at the cusp centers to aid in 
bioprosthesis orientation and suture placement. 
The Model 11000A valve is treated with a new tissue process that builds on Edwards’ existing tissue 
process, ThermaFix (TFX). The new process allows the valve to be stored in non-aqueous packaging and 
the valve is ethylene oxide sterilized. 
Edwards Pericardial Mitral Bioprosthesis 
The Edwards Pericardial Mitral Bioprosthesis, Model 11000M is a bioprosthesis comprised of bovine 
pericardium. It is based on the same design as the Carpentier-Edwards PERIMOUNT Magna Mitral Ease 
Pericardial Bioprosthesis, Model 7300TFX, which was approved under P860057/S068 on 24 June 2010. 
The physical structure and design of the Model 11000M is identical to the Model 7300TFX, except for 
tissue processing, sterilization and packaging. The Edwards Pericardial Mitral Bioprosthesis, Model 
11000M, is a trileaflet bioprosthesis comprised of treated bovine pericardium that is mounted on a flexible 
frame. It is available in sizes 25, 27, 29, 31, and 33 mm. The bioprosthesis is stored in non-aqueous 
packaging, and does not require rinsing prior to implantation. 
The wireform is made of a cobalt-chromium alloy and is covered with a woven polyester fabric. A cobalt 
chromium alloy/polyester film laminate band surrounds the base of the wireform frame. A waffled silicone 
sewing ring that is covered with a porous polytetrafluoroethylene (PTFE) cloth is attached to the wireform 
frame. The sewing ring is scalloped along its anterior portion. Black silk suture markers on the anterior 
portion facilitate the orientation of the bioprosthesis and help avoid obstruction of the left ventricular 
outflow tract by a strut. A black silk suture guide line circles the sewing ring. 
The Model 11000M valve is treated with a new tissue process that builds on Edwards’ existing tissue 
process, ThermaFix (TFX). The new process allows the valve to be stored in non-aqueous packaging and 
the valve is ethylene oxide sterilized. 
 
5.2.1 
DEVICE INDICATION FOR USE 
The Edwards Pericardial Aortic Bioprosthesis, Model 11000A, is indicated for patients who require 
replacement of their native or prosthetic aortic valve. The device is contraindicated only if the implanting 
surgeon decides the anatomy and pathology pose unwarranted risk. 
The Edwards Pericardial Mitral Bioprosthesis, Model 11000M, is indicated for patients who require 
replacement of their native or prosthetic mitral valve. The device is contraindicated only if the implanting 
surgeon decides the anatomy and pathology pose unwarranted risk. 

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5.2.2 
DEVICE TRAINING 
Training on the Model 11000A and Model 11000M will be per the Instructions for Use (IFUs) provided in 
Attachment B. The implant technique for the Model 11000A and Model 11000M is the same as other 
supraannular bioprosthetic valves.  The only usage difference in Model 11000A and Model 11000M from 
other tissue valves is that Models 11000A and 11000M do not require rinsing prior to implantation. If the 
bioprosthesis is rinsed prior to implantation, the valve must then be kept hydrated with sterile 
physiological saline irrigation on both sides of the leaflets until the heart is closed. 
5.3 
REPORT OF PRIOR INVESTIGATIONS 
A clinical trial (Protocol Number 2010-03) initiated in Europe in July 2011 is underway to gather data on 
the Model 11000A. This is a prospective, non-randomized clinical trial of the investigational valve for 
subjects undergoing aortic valve replacement (AVR). This trial is an observational, confirmatory trial and 
not powered for statistical analysis. To date, the trial has enrolled one hundred thirty three (133) subjects 
at two (2) investigational sites in Poland. There are three (3) early deaths, of which two (2) deaths were 
adjudicated by the CEC as not related to the valve, and one (1) death was adjudicated as valve related.  
There are sixteen (16) late deaths, of which three (3) have been adjudicated as valve related. One (1) 
incident of late study valve related mortality was adjudicated to be due to valve thrombosis, one (1) was 
adjudicated as to be due to nonspecific/unknown cause, and one (1) valve-related late death was 
adjudicated to be due to cardiac arrest.  As of 7 April 2017, 100% of the eligible subjects completed the 
discharge, 99.2% completed the 3 month, 97.6% completed the 1 year follow-up, 92.5% completed the 2 
year follow-up, 93.8% completed the 3 year follow-up, 92.7% of eligible subjects completed the 4 year 
follow-up, and 100% completed the 5 year follow up visits. At the time of this interim report there are no 
occurrences of study valve related bleeding, hemolysis, structural valve deterioration or unanticipated 
adverse device effects. 
 
 
 

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6.2 
RISKS 
As with all prosthetic heart valves, serious complications, sometimes leading to death may be associated 
with the use of tissue valves. Complications due to individual subject reaction to an implanted device, or 
to physical or chemical changes in the components, particularly those of biological origin, may occur at 
varying intervals (hours or days) necessitating reoperation and replacement of the prosthetic device. 
Some or all of the risks listed below could require a reoperation or explant, and/or they may lead to 
permanent disability or death. 
Known/potential risks associated with stented bioprosthetic heart valves include but not limited to: 
 Angina 
 Bleeding diatheses (coagulopathy) related to 
anticoagulant therapy 
 Cardiac arrhythmias 
 Cardiac failure 
 Coronary ostial blockage 
 Endocarditis 
 Hemolysis/Hemolytic anemia 
 Hemorrhage 
 Immunological response 
 Leaflet entrapment (impingement) 
 Myocardial infarction 
 Nonstructural valve dysfunction 
 Paravalvular/Perivalvular leak 
 Malfunctions of valve due to distortion at 
implant, fracture of wireform, physical and or 
chemical deterioration of valve components 
 Patient prosthetic mismatch (PPM) 
 Regurgitation/insufficiency  
 Stenosis 
 Thromboembolism/stroke 
 Tissue deterioration including infection, 
calcification, thickening, perforation, 
degeneration, suture abrasion, instrument 
trauma, and or leaflet detachment 
 Transient ischemic attack (TIA) 
 Valve pannus 
 Valve thrombosis 
 
Potential risks associated with aortic valve replacement surgery include but not limited to: 
 Allergic reaction 
 Annular dissection 
 Aortic dissection 
 Arterial dissection  
 Bleeding, anticoagulant related  
 Bleeding, procedural  
 Bleeding, post‐procedural  
 Cardiac arrest 
 Cardiogenic shock 
 Disseminated intravascular coagulation 
(DIC) 
 Esophageal rupture 
 Heart failure 
 Hypoxemia 
 Infection, local or wound 
 Infection, systemic (septicemia) 
 Myocardial infarction 
 Multi-system organ failure (MOF) 
 Pericardial effusion 
 Pericardial tamponade 
 Pleural effusion 
 Pulmonary edema 
 Pneumonia 
 Renal dysfunction 
 Respiratory failure 

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 Hematoma 
 Heparin induced thrombocytopenia (HITs) 
 Hypotension 
 Hypertension 
 Thromboembolism 
– Venous, peripheral or central 
– Arterial, peripheral or central 
– Pulmonary, thrombus or other 
Risks associated with Models 11000A and 11000M are anticipated to be the same as those listed above 
for other aortic or mitral bioprosthetic valves and valve replacement surgery.  Based on pre-clinical 
testing, it is not anticipated that any new risks associated with the Model 11000A and Model 11000M 
tissue process, sterilization method, or packaging will be observed. 
6.3 
MINIMIZING SUBJECT RISK 
Several safeguards are incorporated into the trial to minimize subject risk. The pre-clinical device testing 
for the implantable valve was performed in accordance with FDA guidance, ISO 5840:2009 and recognized 
product standards. All test results met or passed the required specifications supporting reasonable safety 
for this investigational product.  
This clinical trial is conducted under the direction of qualified physicians experienced with cardiac surgery 
including aortic and mitral valve repair/replacement and the use of investigational devices. All 
participating investigators and sites are screened and qualified. They must be experienced in conducting 
clinical research and have adequate personnel to assure compliance to the trial protocol. No special 
training is required to implant the Models 11000A and 11000M. The Instructions for Use (Attachment B) 
provide detailed instructions on the proper handling and implantation of these investigational valves.  
7.0  TRIAL DESIGN 
This trial design methodology is based on a one year structural valve deterioration primary endpoint, as 
discussed in Sections 7.3.1 and 9.0. Based on the results of a pre-clinical assessment and OUS clinical trial, 
the use of the investigational valve is justified. 
7.1 
OBJECTIVE 
The objective of this trial is to confirm that the modifications to tissue processing, valve sterilization, and 
packaging of the FDA-approved (P860057/S042) Carpentier-Edwards PERIMOUNT Magna Ease Pericardial 
Aortic Bioprosthesis, Model 3300TFX, which will be designated as the Edwards Pericardial Aortic 
Bioprosthesis Model 11000A, and the Carpentier-Edwards PERIMOUNT Magna Mitral Pericardial 
Bioprosthesis, Model 7300TFX, which will be designated as the Edwards Pericardial Mitral Bioprosthesis 
Model 11000M do not raise any new questions of safety and effectiveness in subjects who require 
replacement of their native or prosthetic aortic or mitral valve. The only differences between the Model 
3300TFX and Model 11000A, and Model 7300TFX and 11000M are modifications in tissue processing, 

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valve sterilization, and packaging. The primary safety hypothesis to be accepted or rejected by statistical 
data is provided in Statistical Methods Section 9.0. 
7.2 
DESIGN 
The trial is a multicenter, prospective, double arm trial to be conducted throughout the United States, 
Canada, Europe and Asia Pacific. It will include subjects with valve stenosis or insufficiency, or stenosis 
plus insufficiency requiring a planned valve replacement of their native or prosthetic valve. Final analysis 
for the aortic arm will be performed when at least three hundred (300) AVR subjects have completed the 
POD 390 follow-up visit, and at least 800 AVR patient-years of cumulative follow-up have been reached. 
Analysis for the mitral arm will be completed when at least three hundred (300) combined aortic and 
mitral subjects have completed the POD 390 follow-up visit and at least eight hundred (800) AVR and at 
least one hundred (100) MVR patient-years of cumulative follow-up have been reached. The tests for the 
trial endpoints were performed and the trial data was submitted to FDA for the PMA approval of the 
devices evaluated under the aortic and mitral arms. All IDE Subjects (aortic and mitral arms) who are 
currently enrolled and alive will be followed to 5 years. In an effort to obtain sufficient long-term data,  
approximately 250 Subjects implanted with the Model 11000A valve at up to 10 sites will be asked to 
consent for extended follow-up annually through 10 years post-procedure. In addition, approximately 25 
Subjects implanted with the Model 11000M valve at select sites will be asked to consent for extended 
follow-up annually through 10 years post-procedure. 
7.3 
ENDPOINTS 
All safety and effectiveness data for the Model 11000A and Model 11000M valves will be compared to 
control data published in articles in the prosthetic heart valve literature. 
 
 

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7.3.1 
SAFETY 
Primary Safety Endpoint (up to 390 days post-implant): 
The primary safety endpoint for the trial is the rate of implanted subjects that experience structural 
deterioration of the trial valve by the time of the POD 390 follow-up visit. The null hypothesis is that the 
rate of structural valve deterioration at one year is greater than 1%. The alternative hypothesis is that this 
rate is less than 1%.  
Primary Safety Endpoint (Continued follow-up): 
For continued follow-up of Subjects, the primary safety endpoint for the trial is the rate of implanted 
subjects that experience structural deterioration of the trial valve as determined by a Clinical Events 
Committee (CEC). 
Secondary Safety Endpoints (Pre-approval):  
Safety will be established by comparing the occurrence of specific safety endpoints to the objective 
performance criteria (OPC) reported in Table R.1 in ISO 5840:2009, Annex R.1 as recommended by the 
FDA in the Draft Guidance involving Heart Valves – Investigational Device Exemption (IDE) and Premarket 
Approval (PMA) Applications issued January 20, 2010.   
Secondary Safety Endpoints (Continued follow-up):  
For continued follow-up of Subjects, linearized rates will be used to summarize the following safety 
endpoints for the late (>30 days) post-operative period. 
 Thromboembolism 
 Valve thrombosis 
 All bleeding/hemorrhage 
 Major bleeding/hemorrhage 
 All paravalvular leak  
 Major paravalvular leak  
 Non-structural valve deterioration 
 Endocarditis 
 All-cause mortality 
 Trial valve-related mortality 
 Trial valve-related reoperation 
 Explant  
 Hemolysis 
The Data Monitoring Committee (DMC) will review aggregate safety and hemodynamic data to determine 
if the trial is being conducted safely and in accordance to the protocol. The DMC will decide if the clinical 
investigation should be modified, suspended and or stopped. 
The Clinical Events Committee (CEC) evaluates the adverse events that are endpoint related as well as 
those resulting in death. The CEC adjudicates early and late events for their relatedness to the 
investigational device and/or the surgical procedure.    
Adverse event categories are provided in Section 11.0 and definitions are provided in Attachment H – 

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Adverse Effect (Codes and Definitions). 
7.3.2 
EFFECTIVENESS 
Effectiveness endpoints include the following:  
• 
Clinically acceptable hemodynamic performance confirmed by echocardiography and core lab 
evaluation which will include the following parameters: 
– 
Mean gradient 
– 
Peak gradient 
– 
Effective orifice area [EOA] 
– 
EOA index 
– 
Performance index 
– 
Cardiac Output [CO] 
– 
Cardiac index 
– 
Valvular regurgitation including 
paravalvular leak 
• 
New York Heart Association (NYHA) functional class compared to baseline 
• 
Change in Quality of Life assessment – Short Form 12 version 2 (SF-12v2) score from baseline to 
POD 390. 
7.4 
ADDITIONAL CLINICAL MEASURES 
Additional Data in support of analysis: 
• 
Blood Data 
– 
White Blood Cell Count 
– 
Red Blood Cell Count 
– 
Hemoglobin 
– 
Hematocrit 
– 
Platelet Count 
– 
Plasma free hemoglobin or haptoglobin or serum LDH 
– 
Coagulation profile (If collected per standard of care dependent on anticoagulation 
regimen) 
– 
Serum Glycerol (See Section 10.4.1 for details) 
 
 
7.5 
NUMBER OF SUBJECTS 
Up to seven hundred (700) aortic valve replacement (AVR) subjects and up to one hundred seventy five 
(175) mitral valve replacement (MVR) subjects at up to forty (40) clinical sites will be enrolled. At least 
eight (8) centers will implant thirty (30) or more AVR or thirty (30) or more AVR/MVR subjects with one 
year follow-up.   An enrollment rate of three (3) to four (4) subjects per site per month is anticipated.  Sites 
with less than ten (10) subjects enrolled will have data combined and reported.  Enrollment period 
completion is anticipated within 1095 days or three (3) years. 

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7.6 
METHODS OF FOLLOW-UP 
Following informed consent and determination of eligibility, subjects undergo a pre-operative 
echocardiogram to document the function of their current valve prior to surgery. Evaluation of the 
echocardiogram (echo) is performed by a qualified cardiologist/sonographer at the site and over read by 
an independent core lab. Other baseline exams include physical assessment, recording of pertinent 
medical history, electrocardiogram (ECG), NYHA classification, Canadian Cardiovascular Society (CCS) 
Angina classification, quality of life (QOL) assessment, and selected hematological variables. 
During the procedure, a transesophageal echo (TEE) and blood collection (if applicable, see Section 10.4.1) 
will be completed, and a post-operative ECG/rhythm strip will be conducted upon admission to the 
intensive care unit. In addition, follow-up will occur at or prior to hospital discharge where physical 
assessment, NYHA classification, CCS Angina classification, ECG, echo and evaluation of selected 
hematological variables will occur. A post-op echocardiogram must be completed on or prior to post-
operative Day 10.  At POD 30, a phone follow-up will assess NYHA classification and information on any 
adverse events that have occurred since discharge. At POD 105 follow-up visit, a physical assessment, 
NYHA classification, ECG, echocardiogram, and selected hematological variables will be evaluated. The 
subsequent follow-up visits will be made at POD 390, and annually thereafter up to POD 1825 or 3650.   
Table 2 lists the follow-up visit time points and visit windows. 
Adverse events and anti-thromboembolic therapy/medications are collected from the time of the index 
procedure until the subject exits the clinical trial.  
 
 

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4. Requires a surgical procedure outside of the cardiac area (e.g. vascular bypass) 
5. Requires surgical replacement of the aortic root 
6. Has active endocarditis/myocarditis or endocarditis/myocarditis within 3 months to the scheduled aortic 
or mitral valve replacement surgery 
7. Has renal insufficiency as determined by creatinine (S-Cr) level ≥ 2.5 mg/dL or end-stage renal disease 
requiring chronic dialysis at screening visit 
8. Has MRI or CT scan confirmed stroke, cerebrovascular accident (CVA) or transient ischemic attack (TIA) 
within 6 months (180 days) prior to planned valve surgery  
9. Has acute myocardial infarction (MI) within 30 days prior to planned valve surgery 
10. Has presence of non-cardiac disease limiting life expectancy to less than 12 months 
11. Diagnosed with hypertrophic obstructive cardiomyopathy (HOCM) 
12. Diagnosed with abnormal calcium metabolism and hyperparathyroidism 
13. Exhibits left ventricular ejection fraction ≤ 20% as validated by diagnostic procedure prior to planned valve 
surgery 
14. Echocardiographic evidence of an intra-cardiac mass, thrombus, or vegetation 
15. Hemodynamic or respiratory instability requiring inotropic support, mechanical circulatory support, or 
mechanical ventilation within 30 days prior to planned valve surgery 
16. Documented leukopenia (WBC < 3.5x 103/µL), acute anemia (Hgb < 10.0 gm/dL or 6 mmol/L), or 
thrombocytopenia (platelet count < 50x103/µL) accompanied by history of bleeding diathesis or 
coagulopathy 
17. Has prior organ transplant or is currently an organ transplant candidate 
18. Current or recent participation (within 6 weeks prior to surgery) in another drug or device trial 
19. Was previously implanted with investigational device (Model 11000A or Model 11000M)2 
20. Pregnant (female subject of childbearing potential only), lactating or planning to become pregnant during 
the duration of participation in trial 
21. Currently incarcerated or unable to give voluntary informed consent 
22. Documented history of substance (drug or alcohol) abuse within the last 5 years prior to implant 
23. Requires concomitant left ventricular assist device (LVAD) placement 
 
 
2 Note: Previously implanted means that the index valve replacement procedure was completed. The procedure is complete 
when the surgeon takes the subject off cardiopulmonary bypass and restarts the heart. 

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8.3 
ENROLLED POPULATION 
Subjects will be included in the enrolled population after meeting all the enrollment criteria, signing the 
informed consent, and after the surgeon assesses the subject’s anatomy, sizes the annulus, and 
determines that the trial valve can be implanted. If the surgeon is unable to complete the implant 
procedure, the subject is considered “intent to treat” and will be followed for safety (adverse event 
collection) for 30 days or until any adverse events experienced by subject are resolved. No protocol-
specified tests during this period will be required. 
Each investigator screens subjects for potential inclusion into the trial. Screening results are used to make 
a final determination as to subject suitability for enrollment. Early and late results from this trial (i.e., 
immediate post-operative and up to one year) serve as the basis for determining the safety and 
effectiveness of the Edwards Pericardial Aortic Bioprosthesis, Model 11000A and the Edwards Pericardial 
Mitral Bioprosthesis, Model 11000M. Subjects must meet all applicable inclusion criteria and no pre-
operative exclusion criteria at the time of enrollment evaluation in order to participate. 
8.4 
INDEX VALVE POPULATION 
The investigational valve population includes all enrolled subjects that receive and retain the index valve. 
The analysis of the effectiveness endpoints and of the primary safety endpoint will be based on the 
investigational valve population. 
8.5 
SUBJECT AND TRIAL DURATION 
Total enrollment period for this trial is estimated to be 1095 days or 3 years.  Subject duration in the trial 
is estimated to be no longer than 1825 days (5 years) or 3650 days (10 years) for those who have 
consented to continued follow-up. Overall duration of the trial is estimated to be 3833 days or 10.5 years, 
and will involve at least eight hundred (800) AVR patient-years and at least one hundred (100) mitral valve 
replacement (MVR) patient-years of follow-up.  Trial begins with the enrollment of the first subject and 
ends after the last subject is exited from the trial after completing the last follow-up visit at approximately 
POD 3650, all subjects are fully monitored, all outstanding data queries are resolved and all trial sites are 
closed to follow-up. 
8.6 
SUBJECT TERMINATION OR WITHDRAWAL 
Once enrolled, subjects may discontinue participation at any time by withdrawing informed consent or 
meeting the requirement for termination. Participation in the trial is entirely voluntary. Subject 
participation for any patient requiring explant or valve-in-valve (ViV) procedure will be terminated at 
either 30 days post-explant/ViV (followed for safety only) or when all post-explant/ViV adverse events are 
resolved (whichever comes last). If the surgeon is unable to complete the implant procedure, those 
subjects are considered enrolled as “intent to treat” and will be followed for safety (adverse event 

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collection) for 30 days or until any adverse events experienced by this cohort are resolved and then will 
be exited from the trial.   
9.0  STATISTICAL METHODS 
9.1 
ANALYSIS POPULATION 
The analysis populations will include the enrolled population and the index valve population. The index 
valve population will include all subjects who meet enrollment criteria, provide written informed consent, 
those deemed able to implant in the operating room and who receive the index valve.  The enrolled 
population will include the index valve population and the “intent to treat” population3.  For the enrolled 
population, the number of patients enrolled per site will be reported. Summaries of baseline and 
procedural data will be based on the enrolled population. The analysis of mortality and all safety data, 
including the primary endpoint, shall in general be based on the index valve population; however, the 
analysis will also be provided using the enrolled cohort. For the investigational valve population, the 
number of subjects implanted per site will be reported, stratified by implant position and valve size within 
each position. 
9.2 
SAMPLE SIZE 
The sample size for this study follows the recommendation from the FDA in the Draft Guidance involving 
Heart Valves – Investigational Device Exemption (IDE) and Premarket (PMA) Applications (2010).  
Assuming the Poisson distribution and the true rate being equal to its OPC, and with probabilities of Type 
I error of 0.05 and Type II error of 0.20, the amount of data necessary to achieve the smallest OPC of 1.2% 
per patient-year (excluding the OPCs for valve thrombosis, major hemorrhage, and major paravalvular 
leak, which are all less than 1.2% per patient-year) is 800 patient-years. 
 
9.3 
STATISTICAL ANALYSIS 
9.3.1 
SAFETY ANALYSIS 
9.3.1.1 
Primary Safety Endpoint (up to 390 days post-implant) 
The primary safety endpoint for the trial is the rate of structural deterioration of the study valve at the 
time of the POD 390 visit. If we let p denote the probability that an implanted subject will experience 
structural valve deterioration by the time of the POD 390 visit, then the null and alternative hypotheses 
for the primary safety endpoint are: 
 
3 If the surgeon is unable to complete the implant procedure, those subjects are considered enrolled as 
“intent to treat” and will be followed for 30 days or until any adverse events experienced by this cohort 
are resolved and then will be exited from the trial. 

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H0: p ≥ 1% 
Ha: p < 1% 
The statistical test of the null hypothesis for the primary safety endpoint is based on a one-sided, upper 
95% confidence interval calculated by the method of Clopper and Pearson9:  
B(0.95; x + 1, n – x) 
Here x is the number of structural valve deteriorations occurring by the POD 390 visit, n is the number of 
patients completing the POD 390 visit, and B(0.95; x + 1, n – x) is the 95% upper quantile of the Beta 
distribution with parameters x + 1 and n – x. If the confidence interval above is less than 1%, then it will 
be concluded with 95% confidence that p is less than 1% and the acceptance criterion for the primary 
safety endpoint will be met. For the purposes of this hypothesis test, both aortic and mitral patients will 
be combined; however, results for the primary safety endpoint also will be reported separately for each 
implant position. 
Based on a simulation, the power of the confidence interval above to reject the null hypothesis is greater 
than 80% for the sample size of 300 patients receiving the POD 390 visit.  The simulation assumed for the 
purposes of power calculation a rate of SVD at the POD 390 visit of 0.05%; if a smaller rate is assumed, 
the power of the statistical test would of course be higher. The code for this simulation has been provided 
to FDA and is included in Attachment O.   
9.3.1.2 
PRIMARY SAFETY ENDPOINT (CONTINUED FOLLOW-UP): 
For continued follow-up of Subjects, the primary safety endpoint for the trial is the rate of implanted 
subjects that experience structural deterioration of the trial valve as determined by a Clinical Events 
Committee (CEC). The linearized rate will be calculated as the number of late events divided by the total 
number of late-subject years. These results will be reported for both implant positions combined and 
separately for each position. 
 
9.3.1.3 
Secondary Safety Endpoints (Pre-approval) 
The secondary safety endpoints listed in Section 7.3.1 will be analyzed using the enrolled population. Early 
adverse events within 30 days of procedure will be reported as the number of events divided by the 
number of enrolled subjects.  Linearized rates will be used to summarize adverse events for the late (>30 
days) post-operative period.  The linearized rates will be calculated as the number of late events divided 
by the total number of late-subject years. In addition, a one-sided upper 95% confidence limit will be 
calculated for the linearized rate.  
The hypotheses for the secondary safety endpoints are: 

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𝐻𝐻0 :𝑝𝑝≥2 × 𝑂𝑂𝑂𝑂𝑂𝑂     𝑣𝑣𝑣𝑣.        𝐻𝐻𝐴𝐴 : 𝑝𝑝 < 2 × 𝑂𝑂𝑂𝑂𝑂𝑂 
 
where p is the complication rate for a given valve-related event. If the one-sided sided upper 95% 
confidence limit for p for a given secondary endpoint is less than  2 × 𝑂𝑂𝑂𝑂𝑂𝑂 then the trial will be considered 
a success with regards to that secondary endpoint.  These hypotheses will be tested based on the 
combined aortic and mitral populations; however the results will also be reported separately for each 
implant position. 
Percentages for the early events and linearized rates for the late events also will be calculated for all other 
complications observed in the trial, including structural deterioration. These results will be reported for 
both implant positions combined and separately for each position. 
Actuarial rates based on the method of Kaplan - Meier will be calculated for SVD and for each of the safety 
events in Section 7.3.1 at each of the follow-up time points; the number of subjects at risk for the event 
will be reported at each of these intervals. These results will be reported for both implant positions 
combined and separately for each position. 
9.3.1.4 
SECONDARY SAFETY ENDPOINTS (CONTINUED FOLLOW-UP):  
For continued follow-up of Subjects, percentages for the early events and linearized rates for the late 
events also will be calculated for all other complications observed in the trial, including structural 
deterioration.  
Actuarial rates based on the method of Kaplan - Meier will be calculated for SVD and for each of the safety 
events in Section 7.3.1 at each of the follow-up time points; the number of subjects at risk for the event 
will be reported at each of these intervals. These results will be reported for both implant positions 
combined and separately for each position. 
 
9.3.2 
EFFECTIVENESS ANALYSIS 
The following effectiveness endpoints will be analyzed using the investigational valve population. The 
analysis for valve performance will be performed separately for each implant position, and the analyses 
for NYHA Class and Quality of Life will be performed for both implant positions combined, separately for 
each position, and for isolated mitral valve replacement and mitral valve replacement with concomitant 
tricuspid valve repair. 
9.3.2.1 
VALVE PERFORMANCE 
The following parameters will be summarized at baseline and at each follow-up visit for all subjects in 
the investigational valve population 

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• 
Peak pressure gradient  
• 
Mean pressure gradient  
• 
Effective orifice area  
• 
Valvular regurgitation 
• 
Effective orifice area index  
• 
Performance index  
• 
Cardiac output  
• 
Cardiac index 
Valvular regurgitation will be summarized by the number and percentage of subjects in each level of 
regurgitation.  All other parameters will be summarized by N, mean, and standard deviation, and a 95% 
confidence interval. These summaries will be stratified by valve size. 
9.3.2.2 
NYHA CLASS 
A comparison of preoperative and postoperative NYHA functional class (presented as the percentage of 
subjects in each class at baseline, at each follow-up time-point, and as the percentage of subjects at each 
follow-up time-point who improved, worsened, or did not change in class) will be presented.  This 
comparison will be based on the investigational valve population.  Additionally, a cross-tabulation of 
baseline vs. POD 390 NYHA will be presented for all subjects in the investigational valve population with 
both baseline and POD 390 NYHA data. 
9.3.2.3 
QUALITY OF LIFE 
The N, mean and standard deviation for the SF-12 physical and mental health summary measures (PCS-
12 and MCS-12, respectively) will be calculated for baseline and POD 390.  In addition, the N and mean 
for the change from baseline to POD 390 in PCS-12 and MCS-12 will be presented with a 95% confidence 
interval. These summaries will be based on the investigational valve population. 
9.4 
ADDITIONAL MEASURES 
9.4.1.1 
BLOOD DATA 
For all measured blood parameters, individual results will be compared to documented normal ranges.  
The Investigator will determine for each parameter that is out-of-range whether the value is not clinically 
significant and summary statistics will be provided.   
Summary statistics (N, mean, and standard deviation) will be calculated preoperatively and post-
operatively.  In addition, the percentage of patient within the normal range preoperatively and post-
operatively will be calculated.  The percentage of patients within the normal range post-operatively will 
be reported separately for patients within and without the normal range preoperatively and for all 
patients combined. 
Analyses of blood data will be performed for both implant positions combined and separately for each 
position. 

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9.5 
POOLABILITY 
Subject baseline risk will be statistically compared between the regions (US, Canada, Europe and Asia 
Pacific) and among centers for the implanted population.  Chi-square tests will be used to compare 
categorical risk factors while analysis of variance will be used to compare continuous risk factors.  
Comparisons will be based on the following demographic and pre-operative variables: age, sex, etiology, 
pre-operative NYHA, and concomitant CABG procedures, and any other baseline risk factors as deemed 
appropriate.   
One-year Kaplan Meier estimates for the implanted population will be compared between the regions 
(US, Canada, Europe and Asia Pacific) and among sites for the following events: thromboembolism, valve 
thrombosis, major bleeding/ hemorrhage, all paravalvular leak, endocarditis, explant, and death.  
Estimates will be compared via a log-rank test. The primary safety endpoint will not be compared between 
regions or sites as it is expected that no structural valve deteriorations will be observed within the first 
year at any site or within any region. 
9.6 
ANALYSIS OF COVARIATES 
A hazard regression analysis will be performed to test for the effect of gender, age at implant, pre-
operative NYHA functional classification, previous valve surgery, concomitant coronary artery bypass 
surgery, implant position, and implant size on survival. This analysis will be performed by using a Cox 
proportional hazards model and will be based on the implanted population. Additionally, one-year Kaplan 
Meier estimates for each of the adverse events listed in the Safety Endpoints Section 7.3.1 will be 
compared between the genders via a log-rank test.   
Finally, the effect of gender on each of the following effectiveness endpoints at POD 390 (1 year) will be 
investigated with a linear regression model: peak gradient, mean gradient, effective orifice area (EOA) 
index.  These linear regression models will be adjusted by BSA (to adjust for the effect of body size), 
implant position, and by valve size.  The effect of gender on all valvular regurgitation at POD 390 (1 year) 
will be investigated via an ordinal logistic regression; this model also will be adjusted by BSA, implant 
position, and by valve size. All analyses will be based on the implanted population.  
9.7 
MISSING DATA 
All statistical tests on the effectiveness endpoints will be performed using only those subjects with 
available data required for endpoint analysis.  No missing value imputation will be performed. 
9.8 
FOLLOW-UP AND COMPLIANCE DATA 
The number of valve population subjects followed to 390 days post-implant will be reported stratified by 
site and valve size; follow-up duration information, including mean follow-up, standard deviation and 
range of follow-up, and cumulative follow-up in subject-years will be reported for the valve population. 

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Subject compliance will be calculated and reported as the following four percentages:  the number of 
subjects a) having completed follow-up visits; b) with NYHA functional classification data; c) with 
echocardiographic data; and d) with clinical laboratory results at each follow-up time-point, divided by 
the total number of implanted subjects available (i.e., who have not died or had their valve explanted) 
and eligible (i.e., who have reached the given time-point) for follow-up at that particular time-point.  
Compliance will be reported for each follow-up visit and will be based on the investigational valve 
population. 
10.0 TRIAL PROCEDURES 
10.1 SUBJECT SCREENING 
All subjects diagnosed with aortic or mitral stenosis, insufficiency or stenosis-insufficiency requiring valve 
replacement as assessed by cardiac surgeons participating in this clinical trial, should be screened for 
eligibility. All subjects who may meet eligibility requirements will be asked to participate.  
A “Screening Log” is provided to the investigational sites to maintain a cumulative log of all screened 
subjects. For subjects who are ineligible for participation in the clinical investigation, a reason supporting 
the disqualification of the subject must be entered on the Screening Log. Sites are not required to enter 
data into the EDC system for any preoperative or intraoperative screen failures. Any subject deemed 
ineligible due to active or recent endocarditis/myocarditis, recent myocardial infarction, pregnancy or 
lactation, or participation in another clinical investigation may be re-screened later. Re-screened subjects 
must be re-entered on the Screening Log.   
10.2 INFORMED CONSENT 
Written informed consent, in accordance with applicable international standards and trial center 
regulations, shall be obtained from each subject, prior to the trial procedures. The investigator retains a 
copy of the signed informed consent document in each subject’s record, and provides a copy to the 
subject.  
The Investigator must obtain the written informed consent of all subjects, and must not allow any subject 
to participate in the investigation prior to obtaining governing institutional review board (IRB), research 
ethics board (REB) approval, or Ethics Committee (EC) approval. Before starting the trial, the investigator 
provides trial Sponsor with a copy of the sample Informed Consent document approved by the IRB, REB, 
or EC with documented evidence that the IRB, REB, or EC approved the protocol and the informed 
consent. 
Attachment C provides an example of a consent form submitted to each IRB, REB, or EC. The example 
form contains the minimal consent language content that must be incorporated into the Informed 

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All efforts should be taken by the Investigator and the research staff to encourage subjects to return for 
required follow-up visits.  If a subject cannot return for follow-up visits, all attempts will be made to collect 
the protocol-specified data from outside hospitals or clinics. For echocardiography exams performed 
outside of the trial site, a copy of the Core Laboratory Procedure Manual is provided in Attachment E to 
ensure compliance with the echocardiography requirements. 
10.8 MISSED FOLLOW-UP 
The Investigator(s) will make every attempt to follow the subjects. All subjects will be encouraged by the 
Investigator(s) to report any address or telephone number changes to the trial site. They are informed of 
the importance of returning for scheduled follow-up visits even if they are not having any medical issues. 
If a subject cannot be reached for a follow-up visit, the Investigator will document on the CRF, the efforts 
undertaken to contact the subject or the subject’s primary health care provider. These efforts should 
include three (3) attempts of telephone contact at separate dates and times, and a registered letter sent 
before the end of the follow-up window (telephone attempts may include a family member if available). 
If a subject cannot be reached for a follow-up visit, or misses a scheduled visit, the visit will be recorded 
as a missed visit on the date of last attempted contact. Subjects who miss a visit will not be considered 
withdrawn. At the next visit interval, the Investigator and/or designee will make three (3) attempts of 
telephone contact at separate dates and times, and a registered letter sent before the end of the follow-
up window (telephone attempts may include a family member if available). Subjects who miss two (2) 
sequential follow-up visits will be considered lost to follow-up at the second missed visit and exempt from 
further trial follow-up. After the subject is terminated from the trial, the Investigator will attempt to 
determine if the subject is alive, including searching national mortality registries as permitted by local 
laws. 
Trial Subjects exit the trial when no additional follow-up visits, procedures, or data collection are required. 
A subject is exited from the trial in the following instances: 
 Fails enrollment criteria after written consent 
 Is Lost-to-follow-up (LTFU) 
 Voluntarily withdraws from the trial  
 Death 
 Explant or valve-in-valve (ViV) intervention (after 30 days for safety endpoints only; or after 
adverse events from explant/ViV are resolved, whichever comes later) 
 Does not retain trial valve after attempt to implant (after 30 days for safety endpoints only; or 
after adverse events from explant are resolved, whichever comes later) 
 Completes last trial follow-up visit (at POD 1825 or POD 3650 for Continued Follow-Up Subjects) 
 Investigator withdraws the subject from the trial 

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10.9 DEVICE REMOVAL OR EXPLANT 
Index valve ‘removal’ is the excision of the investigational valve, before implant of the investigational valve 
is complete, i.e., the subject does not leave the OR with the investigational valve. If the surgeon is unable 
to satisfactorily position or sew in the index valve, it will be removed and returned to the trial Sponsor 
who will provide a return valve kit.  If the subject leaves the OR with the investigational valve in place, the 
valve will be considered implanted and if removal is required from this point forward, it will be considered 
an explant. 
In the event a valve is explanted/ requires a valve-in-valve intervention, a copy of the procedure report 
must be provided to the trial Sponsor. Information on the cause of explant and its relationship to the valve 
will be provided by the investigator(s). Explanted valves must be returned to the trial Sponsor for analysis. 
Return kits for devices will be provided by the trial Sponsor. 
11.0 ADVERSE EVENTS 
11.1 REPORTING 
Adverse event information is reported throughout the clinical investigation. Adverse events are followed 
until they are adequately resolved. A list of potential adverse events, which may result from the trial 
procedure, are included in the Risk Section 6.2, the Instructions for Use (IFU) in Attachment C, and further 
defined in Attachment G. 
11.1.1 UNANTICIPATED ADVERSE DEVICE EFFECT 
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 the device, if that effect, problem, or death 
was not previously identified in nature, severity, degree of incidence in this Investigational Plan. 
Additionally, an unanticipated adverse event includes any other unanticipated serious problem associated 
with the device that relates to the rights, safety, or welfare of subjects.   
Investigator(s) are required to submit to the reviewing IRB/REB/EC and the trial Sponsor a report of any 
unanticipated adverse device effect (UADE) occurring during this investigation as soon as possible, but in 
no event later than two (2) business days after the investigator(s) first learns of the effect (21CFR 
812.150(a)(l)).  The trial Sponsor must immediately conduct an evaluation of an UADE, and must report 
the results of the evaluation to FDA, all reviewing IRB/REB/ECs, and participating investigators within ten 
(10) business days after the trial Sponsor first receives notice of the effect (21CFR 812.46(b), 
812.150(b)(l)). 
If it is determined that an UADE occurred, the trial Sponsor will notify the Data Monitoring Committee 
(DMC) within five (5) business days after the trial Sponsor or its designee first receives notice of the event. 
If the trial Sponsor and/or the DMC determines an event or event rate presents an unreasonable risk to a 

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subject, all investigations or parts of investigations presenting that risk are terminated, as soon as 
possible. Termination of the investigation shall occur no later than five (5) working days after the trial 
Sponsor makes this determination and no later than fifteen (15) days after trial Sponsor or its designee 
first receives notice of the event. 
11.1.2 ADVERSE DEVICE EFFECTS 
An adverse event is any undesirable experience associated with the use of a medical product in a patient. 
The event is serious and should be reported to FDA (and other relevant regulatory agencies) when the 
subject outcome is/led to: 
• 
Death 
• 
Life-threatening 
• 
Hospitalization or prolonged hospitalization 
• 
Disability or permanent damage 
• 
Congenital Anomaly or birth defect 
• 
Intervention to prevent permanent impairment or damage 
• 
Other serious or important medical events – medical or surgical intervention to prevent one of 
the above outcomes 
. 
Investigational sites report all applicable serious adverse events in accordance with the reviewing 
IRB/REB/EC committee’s requirements. 
Trial Sponsor or its designee determines reportability of applicable adverse events according to its 
responsibilities for European vigilance reporting. 
11.2 NOTIFICATION OF UADE AND/OR SERIOUS DEVICE RELATED ADVERSE EFFECTS 
Notification of UADE and serious device related adverse effects should be done via email to 
HVTClinicalResearch@edwards.com  or faxed to 949-809-5610. 
11.3 DEATH AND EXPLANTS 
In the event of subject death, every effort should be made to obtain a copy of the autopsy report and/or 
death summary. Information on the cause of death and its relationship to the device used in this clinical 
trial will be determined by the investigator(s). Copies of an autopsy report, if available, and/or a death 
summary are to be sent to the trial Sponsor.  
If a device is explanted during autopsy, the device should be returned to the trial Sponsor for analysis. 
Return kits for devices will be provided by the trial Sponsor.  
 

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11.4 DATA MONITORING COMMITTEE 
The trial Sponsor will appoint a Data Monitoring Committee (DMC) composed of two or more independent 
physicians including a cardiothoracic surgeon and a cardiologist, and a statistician. Members of the DMC 
will not have scientific, financial, or other conflict of interest related to the trial Sponsor or the 
Investigators. Curricula Vitae for the DMC members are maintained by the trial Sponsor, and are available 
for regulatory review. These individuals may not participate in this trial as investigators, and may not hold 
significant material, financial or other interests, which create a potential conflict with respect to this role. 
DMC members must sign a non-conflict-of-interest statement in this regard. 
The primary purpose of the DMC is to ensure a consistent, independent review of events and their clinical 
significance using standardized criteria and definitions. The DMC will be tasked with identifying any issues 
such as higher than expected AE and/or death rates, UADEs or hemodynamic performance that is 
substantially worse than expected, to determine if the trial should be stopped, suspended, or modified at 
any time. The DMC will establish guideline criteria for recommending trial termination. 
The DMC will meet at least yearly or more often as determined by the Chairperson and possibly on an ad 
hoc basis to evaluate trial progress and results during the enrollment phase. The Chairperson of the DMC 
will be informed of all UADEs within five (5) business days of these events being reported to the trial 
Sponsor or its designee. This requirement, in addition to the guideline criteria for recommending trial 
termination, will be incorporated into the DMC charter. 
11.5 CLINICAL EVENTS COMMITTEE 
The Clinical Events Committee (CEC) evaluates adverse events that are endpoint related. The CEC 
adjudicates events for their relatedness to the investigational device and/or the surgical procedure. The 
CEC will be composed of physicians familiar with the treatment of valvular heart disease and cardiac 
surgery and who are not participating in the investigational trial. 
The trial Sponsor will provide the CEC completed case report forms and any relevant source 
documentation/subject information as provided by the clinical site investigators. The trial Sponsor will 
insure that all information is de-identified before presenting to the committee. The CEC documents its 
findings or rulings on each event. All meeting minutes and supporting documentation are maintained by 
the CEC administrator with a copy provided to the trial Sponsor.  

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12.0 TRIAL AND DATA MANAGEMENT 
12.1 TRIAL CORE LABS 
12.1.1 ECHOCARDIOGRAPHY CORE LAB 
The Echocardiography Core Lab is responsible for independently evaluating echocardiograms submitted 
preoperatively and postoperatively by trial sites, and for reporting of hemodynamic and other valvular 
function results. The purpose of the Echocardiography Core Lab is to ensure unbiased, timely and 
consistent analysis of the diagnostic data, and for evaluating changes in subject status over the course of 
the trial based on serial echocardiographic studies conducted on the same subject. 
Personnel at the Echocardiography Core Lab must demonstrate appropriate training and experience for 
analyzing Doppler Echocardiography data. The trial Sponsor or its designee periodically will audit the 
Echocardiography Core Lab.  Echocardiograms will be sent directly from the investigational sites to the 
Echocardiography Core Lab. The Echocardiography Core Lab reviews the Doppler echocardiograms upon 
receipt, and promptly notifies the site and the trial Sponsor if the quality of the echocardiograph is 
insufficient for analysis.  The Echocardiography Core Lab will enter the data into the eCRF. See Attachment 
E for the Core Laboratory Procedure Manual. 
12.1.2 GLYCEROL ASSESSMENT CORE LAB 
The Glycerol Assessment Core Lab is responsible for independently analyzing all blood samples collected 
for measurement of serum glycerol. The purpose is to ensure unbiased, timely and consistent analysis of 
the data. See Attachment F for the Serum Glycerol Sample Collection Manual.  
 
12.2 DEVICE ACCOUNTABILITY 
An initial set of Edwards Pericardial Bioprostheses Models 11000A and/or 11000M, is shipped to the 
clinical site once the following conditions are met: the site obtained regulatory approval (Institutional 
Review Board, Ethics Committee approval or Research Ethics Board), a signed Clinical Trial Agreement is 
in place, and the Site Initiation Visit, including Principal Investigator training, is complete. Additional 
devices are sent to the clinical site as devices are used or as needed. 
12.2.1 INVENTORY AND ACCOUNTABILITY RECORDS 
A Device Accountability Log is maintained by the Investigator noting all investigational devices received 
for use during this clinical trial. The log is kept with the documents for the clinical trial and is available for 
review during trial Sponsor monitoring visits.  
All device shipments include inventory and shipment records (packing slip). The Principal Investigator or 
designee will take inventory of the product,  note the condition of the device, and attest to accuracy of 
the valve shipment by signing the packing slip.  Both the investigational site and the trial Sponsor retain 
copies of the packing slips and the Device Accountability Log. 

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12.2.2 DEVICE STORAGE 
The device inventory is to be stored in a locked, controlled, cool, dry and clean area. This storage area 
shall be accessible only to the Principal Investigator(s), Co-Investigator(s) or approved designee(s). Only 
cardiac surgeons identified in the Clinical Trial Agreement and/or on the Delegation of Authority form on 
file may implant the investigational device. 
12.2.3 DEVICE RETURN 
The Principal Investigator(s) is notified in writing upon termination of the clinical trial. All unused devices 
in original package and/or those in opened packages will be returned upon receipt of this notice as 
described in the IFU. The Investigator’s copy of the Device Accountability Log must document any unused 
devices that are returned. The trial Sponsor will provide shipping instructions. 
12.3 PROTOCOL DEVIATIONS 
A protocol deviation is defined as an event where the Investigator or trial personnel did not conduct the 
trial according to the clinical protocol or the Clinical Trial Agreement.  
Deviations shall be reported to the trial Sponsor regardless of whether medically justifiable or taken to 
protect the subject in an emergency. Subject specific deviations and non-subject specific deviations, (e.g. 
unauthorized use of a trial device outside the trial, unauthorized use of a trial device by a physician who 
is not listed in the Clinical Trial Agreement, etc.) will be reported in writing. Investigators will adhere to 
procedures for reporting trial deviations to the IRB/EC/REB in accordance with their specific reporting 
policies and procedures. 
For reporting purposes, deviations are classified as major or minor: 
• Major deviations – will be reported to the trial Sponsor within 48 hours but no later than 3 business 
days of awareness of the major deviation and document on the appropriate case report form 
provided; and to the IRB/REB/EC per their guidelines 
– 
Any deviation from subject inclusion and exclusion criteria 
– 
Any deviation from subject informed consent procedures 
– 
Unauthorized use of an investigational device outside the trial 
– 
Unauthorized use of an investigational device by a physician who is not listed in the Clinical Trial 
Agreement 
 
• Minor deviations – will be reported to the trial Sponsor in writing on the appropriate form provided    
– 
Deviation from a protocol requirement such as incomplete/inadequate testing procedures; 
– 
Follow-up performed outside specified time windows in the protocol  
NOTE: Information that is not essential to the trial endpoints is not considered a deviation if absent. 

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12.4 TRIAL SITE INITIATION AND MONITORING PLAN 
12.4.1 SITE INITIATION AND TRAINING 
Site staff will be trained and experienced to perform their delegated tasks. Training may be in person, 
webinar, read and review, or other methods as deemed appropriate.  
Training is documented on a “Training Log”. A “Delegation of Authority Form” is completed at each site 
designating which individuals are allowed to perform specific clinical trial related tasks. The delegated 
tasks will determine what the training requirements are for each member of the trial support staff.  
New research staff members may be trained by previously trained personnel on the Delegation of 
Authority Form. 
12.4.2 MONITORING 
Written procedures have been established by the trial Sponsor for monitoring clinical investigations, to 
assure the quality of the trial and to assure that each person involved in the monitoring process carries 
out his or her duties. Standardized written procedures, sufficiently detailed to cover the general aspects 
of clinical investigations, will be used as a basic monitoring plan and will be supplemented by more specific 
/ additional procedures specific to this clinical investigation. 
A pre-trial monitoring visit or meeting will be conducted to ensure that the Investigator clearly 
understands and accepts the obligations incurred in undertaking the clinical investigation as listed in Table 
7 (Regulations and Guidelines), and that the facilities are acceptable.   Periodic monitoring visits will be 
conducted with adequate frequency to ensure that the Investigator’s obligations as set forth in 21 CFR 
Part 56 and 21 CFR Part 812 are being fulfilled and that the facilities continue to be acceptable.  
The trial Sponsor will assign a monitor to oversee the progress of the clinical investigation at each 
investigational center. The monitor will remain in close contact with each investigational center 
throughout the duration of the investigation to provide any needed materials, (i.e., investigation forms) 
and answer any questions. The monitor will be responsible for verifying that the subject signed the 
consent, reviewing all data recorded on the eCRFs, and visiting each investigational center periodically to 
observe trial progress and compliance with clinical protocol and regulations applicable to this clinical 
investigation.  Additionally, the monitor will provide assurance that complete records are being 
maintained, appropriate timely reports are made to the trial Sponsor and IRB/REB/EC, device inventory is 
controlled, and that the Investigator is carrying out all agreed upon activities. Any personnel changes must 
be reported to the monitor immediately and a training program must be scheduled and documented.   A 
trial termination monitoring visit will be conducted at the completion of the clinical trial to ensure that all 
data are properly documented and reported. 

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Site Termination: If a clinical monitor becomes aware that an Investigator is not complying with the signed 
Investigator’s Agreement, the Investigational Plan, the requirements of applicable health authority 
regulations, or any conditions of approval imposed by the reviewing IRB/REB/EC or health authority, trial 
Sponsor will immediately either secure compliance or terminate the Investigator’s participation in the 
trial. The final action will be taken with the goal of assuring the rights, safety and welfare of the patients. 
12.5 DOCUMENTATION REQUIREMENTS 
12.5.1 SOURCE DOCUMENTS 
Clinical regulations require that Investigators maintain information in the clinical trial subject’s medical 
records that corroborate data collected on the eCRF. Some examples of critical information to be 
maintained for review by the regulatory inspectors and trial Sponsor monitors are: 
• 
Medical history and physical condition of the clinical trial subject before involvement in the clinical 
trial sufficient to verify protocol entry criteria  
• 
Dated and signed notes in the subject’s medical record on the day of entry into the clinical trial 
• 
Dated and signed notes, laboratory records, and test reports, from each clinical subject visit with 
reference to the eCRF for further information, if appropriate (for specific results of procedures 
and exams). 
• 
Notations on abnormal lab results, adverse events reported and their resolution 
• 
Notes regarding concomitant anticoagulant/antithrombotic medications taken during the clinical 
trial 
• 
Subject’s condition upon completion of or withdrawal from the clinical trial. 
To protect subject confidentiality, the subject’s name must not appear anywhere on the imaging media 
sent to trial Sponsor e.g. for reporting serious adverse device effects (SADE), or prepared for evaluation 
by the core lab. Each page should be identified with the subject’s unique trial ID number. All other subject 
identifiers (i.e. medical record number, personal number) are to be obscured. Original copies of all data 
must be kept at the site. 
Site monitoring will include 100% primary source verification of events contributing to the safety and 
effectiveness endpoints and unanticipated adverse device effects (UADE).  
12.5.2 TRIAL DOCUMENTS 
The trial Sponsor will provide pre-printed forms to each trial site for documentation of: 
• 
Investigator and site training to the protocol (Training Log) 
• 
Authorized trial site personnel (Delegation of Authority) 

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• 
Subject consent and screening (Screening and Enrollment Log) 
• 
Monitoring visit tracking (Site Visit Log) 
• 
Investigational Device Accountability (Investigational Device Accountability Log) 
The site visit is recorded on the appropriate site visit report. All tasks and action items noted during the 
visit should be documented with detailed findings and comments provided as appropriate. The monitor 
provides a visit follow-up letter to the investigator and other appropriate trial staff briefly summarizing 
the visit and specifically addressing any outstanding issues and/or action items from the visit, any incidents 
of noncompliance with the protocol or applicable regulations noted during the visit, and any necessary 
corrective actions.  
During the course of the clinical trial, all correspondence (letters, records of telephone calls, emails and 
faxes) regarding the trial must be maintained in the regulatory binder provided by the trial Sponsor. This 
binder must be made available for monitoring visits and audits. 
12.6 DATA COLLECTION 
All required data for this trial are to be collected with standardized Case Report Forms (CRF) for individual 
subjects; the eCRF outline is included in Attachment D. Electronic CRF (eCRF) will be utilized for this trial. 
Each eCRF must be signed electronically by the Principal Investigator listed in the Clinical Trial Agreement 
and Delegation of Authority Log. If for any reason an eCRF is unavailable and/or inaccessible, a paper CRF 
will be provided by the trial Sponsor to be completed, signed by the Principal Investigator or designee and 
submitted to the trial Sponsor.  
Case Report Form Instructions will be provided to assist the Investigator(s) and appropriate trial staff with 
the completion of each required eCRF. 
The Sponsor’s data management group is responsible for database development, validation, control and 
management of input from each monitored CRF, issuance and resolution of queries, database 
maintenance, and statistical support.  Data Management personnel will employ a full-featured relational 
Oracle database application (or equivalent) on a central server that is 21 CFR Part 11 compliant. The 
application provides the capability of data collection remotely through the Internet so the participating 
site personnel may log on to the system securely and enter the data. Other data management 
programming and/or data analyses will be done in the database system through the trial Sponsor’s 
internal network.  
12.7 DATA AND DOCUMENT RETENTION 
Trial-related correspondence, subject records, consent forms, records of device implant, and source 
document worksheets are to be maintained on file by the trial site. The trial Sponsor requires that it be 
notified in writing if the Principal Investigator wishes to relinquish ownership of the data and information 

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PAGE 45 OF 47 
 
so that mutually agreed upon arrangements can be made for transfer of ownership to a qualified entity.  
Per FDA regulation 21 CFR 812.140, records of each subject’s participation in the trial must be maintained 
for a period of two (2) years after trial closure and submission of the final report to the IRB/REB/EC.  
12.8 TRIAL PROTOCOL AMENDMENTS 
Changes in the protocol are made only by written amendment agreed upon by the trial Sponsor, the 
applicable regulatory agency, including the United States Food and Drug Administration, and if pertinent, 
the IRB/REB/EC. As appropriate, the trial Sponsor will submit changes in the protocol to the applicable 
regulatory agencies, including the United States Food and Drug Administration and investigators to obtain 
IRB/REB/EC re-approval. A report of withdrawal of IRB, REB or EC approval must be submitted to the trial 
Sponsor within five (5) business days. Any revisions to the protocol, including the Informed Consent Form 
and the Case Report Forms, other than very minor revisions must be approved by trial Sponsor, the 
IRB/EC/REB and the FDA and/or other regulatory agencies. 
12.9 TRIAL COMPLETION 
The principal investigator will be notified in writing upon termination/conclusion of the clinical trial. The 
trial Sponsor retains the right to suspend or terminate this clinical trial at any time.  
A final clinical report shall be compiled once data collection is complete. Such reports include all 
information required and outlined in this protocol. The final report will be provided to regulatory agencies 
and/or institutional review boards/independent ethics committees and other regulatory agencies as per 
applicable laws. The final clinical report will be filed in the clinical trial master file. 
12.10 FUTURE PLANS 
No changes are planned at this time. 
13.0  STATEMENTS OF COMPLIANCE, CONFIDENTIALITY AND RESPONSIBILITIES 
13.1 GOOD CLINICAL PRACTICE STATEMENT 
This trial will be conducted in compliance with all applicable US Federal regulations pertaining to 
investigational devices including but not limited to: 21 CFR Part 50, Part 54, Part 56, Part 812, Good Clinical 
Practice (GCP) standards, and Health and Insurance Portability and Accountability Act (HIPAA). The 
protocol and supporting documents for this trial will be reviewed and approved by an appropriately 
constituted IRB, REB or EC prior to trial initiation. All reviews and approvals will be in accordance with 
Good Clinical Practice (GCP) and all other applicable standards, regulations (local and national), guidelines 
and institutional policies. 

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14.0 PUBLICATIONS 
Edwards Lifesciences, as the trial Sponsor of record, has a proprietary interest in this trial. Authorship and 
manuscript composition will reflect cooperation between multiple investigators and sites, core 
laboratories, and Edwards Lifesciences. Authorship will be established prior to writing of the manuscript. 
No individual publications will be allowed prior to the completion of the final report for this trial and as 
agreed in writing by Edwards Lifesciences.  
15.0 REFERENCES 
1. Rosenhek R, Binder R, Porenta G et al. Predictors of outcome in severe asymptomatic aortic 
stenosis. N Engl J Med 2000; 343(9): 611-7.  
2. Waller BF, Howard J, Fess S. Pathology of mitral valve stenosis and pure mitral regurgitation, part 
I. Clin Cardiol 1994; 17:330. 
3. Waller BF, Howard J, Fess S. Pathology of mitral valve stenosis and pure mitral regurgitation, part 
II. Clin Cardiol 1994; 17:395. 
4. Edward NR et al. Mitral valve repair and replacement in northern New England. American Heart 
Journal 2003; 145(6): 1058-1062. 
5. Horstkotte D, Loogen F. The natural history of aortic valve stenosis. Eur Heart J Supp E 1998;  
57-64.  
6. Carpentier A. Cardiac valve surgery. The French Correction.  J Thorac Cardiovasc Surg 1983; 86: 
323-37. 
7. Carpentier A. Carpentier's Reconstructive Valve Surgery. Maryland Heights: Saunders, 2010. 
8. Craver JM. Aortic valve debridement by ultrasonic surgical aspirator: A word of caution.  Ann 
Thorac Surg 1990; 49: 746-52. 
9. Clopper, C.; Pearson, E. S. (1934). "The use of confidence or fiducial limits illustrated in the case 
of the binomial". Biometrika 26: 404–413. 

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ATTACHMENTS 
 
CONFIDENTIAL AND PROPRIETATARY DATA: This document and the information contained herein may not be reproduced, used, or disclosed 
without written permission from Edwards Lifesciences LLC 
REVISION J: 03 MARCH 2021 
 
 
 
 
ATTACHMENT A – CLINICAL TRIAL SCHEME 
 
 
 

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ATTACHMENTS 
CLINICAL INVESTIGATIONAL PLAN 
PROTOCOL NUMBER: 2012-02 
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REVISION J: 03 MARCH 2021 
 
 
 
CLINICAL TRIAL SCHEME 
Schedule of Tests: 
Baseline 
Procedure 
(Day 0) 
Discharge 
30 Days 
(Phone) 105 Days 390 Days 
730-3650 
Days7 
Signed Informed Consent 
X 
 
 
 
 
 
 
Physical Exam1  
X 
 
X 
 
X 
X 
X 
Medical History2 
X 
 
 
 
 
 
 
Blood Labs3 
X 
X 
X 
 
X 
X 
X 
ECG 
X 
X 
X 
 
X 
X 
X 
Echocardiogram4 
X 
X 
X 
 
X 
X 
X 
NYHA Class/ CCS Angina Class 
X 
 
 
X 
X 
X 
X 
QOL Questionnaire (SF-12 v2) 
X 
 
 
 
 
X 
 
Coagulation Profile5 
X 
 
X 
 
X 
X 
X 
Anti-thromboembolic  
Therapy & Medications 
X 
 
X 
X 
X 
X 
X 
Pregnancy Test6 
X 
 
 
 
 
 
 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
1  Physical exam: height, weight and vital signs [BP, HR]. 
2  Includes cardiovascular & non-cardiovascular conditions, prior cardiac interventions and surgeries. 
3    Blood labs: CBC [RBC, WBC, Hgb, HCT, PLT], plasma free hemoglobin or haptoglobin or serum LDH; Serum 
creatinine is required only at baseline.  
    Serum glycerol is only required at the procedure interval (See Section 10.4.1). 
4  TTE will be the standard echocardiography assessment for the aortic or mitral valve. TEE intra-operatively or 
within 1 hour (from cross clamp removal) to confirm placement of the device and confirm initial function of the 
valve. 
5  Coagulation profile will be determined for subjects on anticoagulant therapy only, where coagulation profile is 
collected per standard of care. Non-Vitamin K oral anticoagulants (NOACs) that do not require monitoring of 
coagulation profile, for example, will not require collection/reporting of coagulation profile. 
6  Applicable only to females of child bearing age.  
7  All IDE subjects to be followed to POD 1825 (5 yrs). All Subjects implanted with the Model 11000A or Model 
11000M valve who have consented to continued follow-up will be followed annually through 10 years post-
procedure. 
 
 

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ATTACHMENTS 
 
CONFIDENTIAL AND PROPRIETATARY DATA: This document and the information contained herein may not be reproduced, used, or disclosed 
without written permission from Edwards Lifesciences LLC 
REVISION J: 03 MARCH 2021 
 
 
 
 
ATTACHMENT B – INSTRUCTIONS FOR USE

3
Note: Based on reports in the literature on tissue valves (Refs.  6, 7, 8, 9 & 10), 
there appears to be an increased incidence of leaflet calcification in patients 
under the age of 20.  In this regard, animal research studies (Ref.  11) show that a 
high systemic calcium level can lead to early calcification.  Furthermore, at least 
one published report describes a potential relationship between the 
consumption of daily calcium supplements and early leaflet calcification in an 
adult (Ref.  13).  When feasible, repeated intravenous injections containing 
calcium should be avoided during the postoperative period; and excessive milk 
or dairy product consumption should be avoided in children.  There are no 
clinical data demonstrating increased resistance of the Edwards Pericardial 
Aortic Bioprosthesis Model 11000A to calcification as compared to other 
commercially available bioprostheses.
5.2	 Potential Adverse Events
Adverse events potentially associated with the use of bioprosthetic heart valves 
include:
• 
Angina
• 
Bleeding diatheses (coagulopathy) related to anticoagulant therapy
• 
Cardiac arrhythmias
• 
Coronary ostial blockage
• 
Endocarditis
• 
Heart failure
• 
Hemolysis
• 
Hemolytic anemia
• 
Hemorrhage
• 
Local and/or systemic infection
• 
Myocardial infarction
• 
Patient prosthetic mismatch (PPM)
• 
Prosthesis leaflet entrapment (Impingement)
• 
Prosthesis nonstructural dysfunction
• 
Prosthesis pannus
• 
Prosthesis perivalvular leak
• 
Prosthesis regurgitation
• 
Prosthesis structural deterioration
• 
Prosthesis thrombosis
• 
Stroke
• 
Thromboembolism
• 
Transient ischemic attack (TIA)
It is possible that these complications may lead to:
 
• 
Reoperation
 
• 
Explantation
 
• 
Permanent disability
 
• 
Death
6.	 Clinical Studies
Pre-Approval Patient Cohort
Clinical data, available on 719 patients requiring isolated aortic valve 
replacement (AVR) with the model 2700 Carpentier-Edwards PERIMOUNT 
pericardial bioprosthesis with mean follow-up of 3. 9 years, indicate overall 
actuarial survival rate at 6 years of 73. 7% ± 2. 0%.  Clinical data, available on 
70 patients requiring double valve replacement (DVR) with mean follow-up of 
3. 7 years, indicate overall actuarial survival rate at 6 years of 67. 2% ± 6. 5%.  
These pre-approval patient cohort data were collected from the period between 
August 1981 to January 1989.  
In the isolated AVR population, there were a total of 455 (63. 3%) males and 264 
(36. 7%) females with a mean age at implant (± standard deviation) of 64 
(± 12. 4) years and a range of 18 to 90 years.  The indications for valve 
replacement were stenosis (63. 4%), regurgitation (16. 3%), mixed disease 
(15. 3%) and previous prosthetic aortic valve dysfunction (5. 0%).  
In the DVR population, there were a total of 24 (34. 3%) males and 46 (65. 7%) 
females with a mean age (± standard deviation) of 62. 9 (± 12. 7) years and a 
range of 31 to 94 years.  The indications for valve replacement were stenosis 
(45. 7%), regurgitation (25. 7%), mixed disease (21. 4%) and previous prosthetic 
aortic valve dysfunction (7. 4%).
The follow-up methods included hospital visits, office visits and contact by 
telephone or letter with either the patient, the patient’s family or local doctor.
Table 2 summarizes the operative and postoperative complication rates for the 
isolated AVR and DVR populations.  The operative rates are based on 
719 patients for the isolated AVR population and on 70 patients for the DVR 
population.  The postoperative rates are based on 2767. 9 and 255. 8 years of 
follow-up occurring > 30 days after implant for the isolated AVR and DVR 
populations, respectively.
Table 3 presents, by valve size, the postoperative echocardiography results of 
patients in this study population.
Information on preoperative and postoperative NYHA Functional Class was 
gathered for the isolated AVR population.  The NYHA Functional Class was not 
reported in 220 patients (171 patients expired and 49 patients not available).  Of 
the 499 patients with reported preoperative and postoperative NYHA Functional 
Class at the last available follow up, 10 patients, (2. 0%) got worse, 59 patients 
(11. 8%) remained the same and 430 patients (86. 2%) improved.
Table 4 presents data comparing preoperative NYHA Functional Class to 
postoperative NYHA Functional Class at the last available follow up.
Post-Approval Patient Cohort
Edwards has followed a post-approval cohort of 267 patients with isolated valve 
replacements (AVR) (model 2700) from four centers of the original clinical trial 
for the Carpentier-Edwards PERIMOUNT pericardial bioprosthesis since 
November 1981.  The population is comprised of 171 (64%) males and 96 (36%) 
females.  The mean age (± standard deviation) of these patients at the time of 
implant was 64. 9 ± 11. 8 years and ranged from 21 to 86 years.  A total of 
2,407 patient years of data were available for analysis (2,386 late patient years).  
Mean follow-up was 9. 0 ± 5. 5 years, with a maximum of 20. 3 years.  A total of 
189 deaths occurred between 1981 and 1994.  Forty-eight (25. 3%) of the 
189 deaths were determined to be valve-related.  The follow-up methods used 
at each clinic included hospital visits, office visits, and contact by telephone or 
letter with either the patient, the patient’s family, or local doctor.  
Table 5 summarizes the freedom from complication rates at 20 years.  Patient 
status as of the last follow-up interval included 189 expired (70. 8%), 10 alive 
(3. 8%), 46 explanted (17. 2%), and 22 lost to follow-up (8. 2%).  

4
There were a total of 48 valve-related expirations in this patient population; 
1 valve-related expiration occurred in the operative period and consisted of 
bleeding.  Twenty-eight postoperative valve-related expirations included 5 due 
to thromboembolism, 4 due to endocarditis/sepsis, 3 due to structural valve 
deterioration and 1 due to bleeding.  There were 15 other expirations that were 
considered to be valve-related because of lack of information or because the 
expiration was classified as valve-related by the investigator.  The actuarial 
freedom from valve-related expiration was 67. 9 ± 6. 6% at 20 years.  Nineteen 
additional expirations were due to either unknown causes or sudden death and 
might have been valve related.  These deaths were conservatively classified as 
valve related; accordingly, the resulting actuarial freedom from valve-related 
expiration was 55. 4 ± 6. 4% at 20 years.  
Improvement in NYHA functional classification also was demonstrated 
postoperatively.  As of the latest follow-up evaluation, 108 patients (44. 8%) 
were in NYHA Functional Class I.  
These data were compiled from a multi-center clinical trial conducted by 
Edwards Lifesciences.  For additional information on this trial, please contact 
Edwards Lifesciences LLC, Heart Valve Therapy Marketing Department, One 
Edwards Way, Irvine, CA 92614-5686.
Confirmatory Study
From August 2003 through January 2004, 60 patients requiring aortic valve 
replacement (AVR) were implanted with the Carpentier-Edwards 
PERIMOUNT Magna aortic bioprosthesis, model 3000, from five institutions (two 
European and three Canadian).  Shortly thereafter, the clinical protocol was 
amended to allow implantation with the Carpentier-Edwards PERIMOUNT Magna 
aortic bioprosthesis, model 3000TFX, and to add three US institutions.  
Subsequently, 193 additional patients were implanted with the model 3000TFX 
from December 2004 through December 2006.  The model 3000TFX differs from 
the model 3000 in that the model 3000TFX is treated with the ThermaFix process.
In the model 3000TFX population, there were a total of 116 males (60. 1%) and 
77 females (39. 9%) with a mean age at implant of 72. 0 (± 8. 59 SD) years and an 
age range from 26 to 89 years.  The main indication for valve replacement was 
stenosis (78. 2%) followed by mixed disease (14. 5%), and regurgitation (7. 3%).
In the combined models 3000 and 3000TFX population, there were a total of 
150 males (59. 3%) and 103 females (40. 7%) with a mean age at implant of 72. 2 
(± 8. 31 SD) years and an age range from 26 to 89 years.  Again the major 
indication for valve replacement was stenosis (77. 5%), mixed disease (15. 4%), 
and regurgitation (7. 1%).
Patients were evaluated preoperatively, intraoperatively, at discharge, at 3 to 
6 months, at 1 year, and annually thereafter.  The cumulative follow-up for the 
model 3000TFX was 167 patient-years, with a mean follow-up of 0. 9 years 
(SD = 0. 42, range = 0. 0 to 2. 1 years); and the cumulative follow-up for both 
models 3000 and 3000TFX combined was 232 patient-years with a mean 
follow-up of 0. 9 years (SD = 0. 42, range = 0. 0 to 2. 1 years).  
Table 6 summarizes early (≤ 30 days) and late postoperative (> 30 days) 
valve‑related adverse event rates for the model 3000TFX and the combined 
models 3000/3000TFX populations, respectively.
Table 7 illustrates, by valve size, hemodynamic variables reported in 
echocardiograms at one year performed on patients in the model 3000TFX and 
the combined model 3000/3000TFX studies.
Table 8 presents the change in NYHA Functional Class from baseline assessment 
to the 1-year visit.  It should be noted that there was a 56. 5% improvement in 
functional class at the 1-year visit for model 3000TFX.  For the model 
3000/3000TFX combined population, there was a 60. 9% improvement in 
functional class at the 1-year visit.
Several published clinical studies demonstrate the long-term durability of 
Carpentier-Edwards PERIMOUNT pericardial aortic bioprostheses, the foundation 
on which the Carpentier-Edwards PERIMOUNT Magna and Magna Ease 
pericardial aortic bioprostheses are designed (Refs.  14, 15, 16 & 17).  
Additionally, published data show the PERIMOUNT Magna aortic bioprosthesis 
demonstrates exceptional hemodynamic performance, with a very low risk of 
patient-prosthesis mismatch (Refs.  18, 19, 20, 21, 22 & 23).
7.	 Individualization of Treatment
Bioprosthetic heart valve recipients should be maintained on anticoagulation 
therapy, except where contraindicated, during the initial stages after 
implantation as determined by the physician on an individual basis.  Long-term 
anticoagulation and/or antiplatelet therapy should be considered for patients 
with risk factors for thromboembolism.  
The ultimate judgment regarding care of a particular patient must be made by 
the healthcare provider and patient in light of all the circumstances presented 
by that patient (Ref.  12).  A bioprosthesis is recommended for AVR in patients of 
any age who will not take warfarin or who have major medical contraindications 
to warfarin therapy.  Patient preference is a reasonable consideration in the 
selection of aortic valve operation and valve prosthesis.  A mechanical prosthesis 
is reasonable for AVR in patients under 65 years of age who do not have a 
contraindication to anticoagulation.  A bioprosthesis is reasonable for AVR in 
patients under 65 years of age who elect to receive this valve for lifestyle 
considerations after detailed discussions of the risks of anticoagulation versus 
the likelihood that a second AVR may be necessary (Ref.  12).
7.1	 Specific Patient Populations
The safety and effectiveness of the Model 11000A bioprosthesis has not been 
established for the following specific populations because it has not been 
studied in these populations:
 
• 
patients who are pregnant;
 
• 
nursing mothers;
 
• 
patients with abnormal calcium metabolism (e.g., chronic renal failure, 
hyperparathyroidism);
 
• 
patients with aneurysmal aortic degenerative conditions (e.g., cystic 
medial necrosis, Marfan’s syndrome);
 
• 
children, adolescents, and young adults
Caution: Based on reports in the literature on tissue valves (Refs.  6, 7, 8, 9 & 10), 
there appears to be an increased incidence of leaflet calcification in patients under 
the age of 20.  When feasible, repeated intravenous injections containing calcium 
should be avoided during the postoperative period, and excessive milk or dairy 
product consumption should be avoided in children.  Animal research studies 
(Ref.  11) show that a high systemic calcium level can lead to early calcification.
8.	 Patient Counseling Information
Careful and continued medical follow up (at least by an annual visit to the 
physician) is advised so that bioprosthesis-related complications, particularly 
those related to material failure, can be diagnosed and properly managed.  
Patients with bioprostheses are at risk from bacteremia (e. g. , undergoing dental 
procedures) and should be advised about prophylactic antibiotic therapy.  Patients 
should be encouraged to carry their Patient Identification Card at all times and to 
inform their healthcare providers that they have an implant when seeking care.
9.	 How Supplied
9.1 	 Packaging
The Edwards Pericardial Aortic Bioprosthesis, Model 11000A, is provided sterile 
and non-pyrogenic, in a double barrier tray package.  The double tray package is 
in a foil pouch, which is in a carton.  

9
12.	 Patient Information
12.1	 Study Identification Card
A Study Identification Card is provided to each subject implanted with the 
Edwards Pericardial Aortic Bioprosthesis, Model 11000A.
12.2	 Patient Information Materials
Patient information materials may be obtained from Edwards or an Edwards 
clinical sales specialist.
13.	 References
1.	 Carpentier, A. , et al.  Biological Factors Affecting Long Term Results of 
Valvular Heterografts.  J Thorac Cardiovasc Surg 1969, 58:467-483.
2.	 Carpentier, A. , et al.  Six Year Follow-up of Glutaraldehyde Preserved 
Heterografts.  J Thorac Cardiovasc Surg 1974, 68:771-782.
3.	 Reis, Robert L. , et al.  The Flexible Stent.  A New Concept in the Fabrication of 
Tissue Heart Valve Prostheses.  J Thorac Cardiovasc Surg 1971, 62(5):683-689 
and 693-695.
4.	 Barratt-Boyes, B. G.  and A. H. G.  Roche.  A Review of Aortic Valve Homografts 
Over a Six and One-half Year Period.  Ann Surg 1969, 170:483-492.
5.	 Brewer, R. J. , et al.  The Dynamic Aortic Root.  Its Role in Aortic Valve 
Function.  J Thorac Cardiovasc Surg 1976, 72:413-417.
6.	 Jamieson,W. R. E. , et al.  Carpentier-Edwards Standard Porcine Bioprosthesis: 
Primary Tissue Failure (Structural Valve Deterioration) by Age Groups.  Ann 
Thorac Surg 1988, 46:155-162.
7.	 Odell, J. A.  Calcification of Porcine Bioprostheses in Children.  In Cohn, L.  and 
V.  Gallucci (eds): Cardiac Bioprostheses.  Yorke Medical Books.  New York, 
1982, pp 231-237.
8.	 Reul, G. J. , et al.  Valve Failure with the lonescu-Shiley Bovine Pericardial 
Bioprosthesis: Analysis of 2680 Patients.  J Vasc Surg 1985, 2(1):192-204.
9.	 Sanders, S. P. , et al.  Use of Hancock Porcine Xenografts in Children and 
Adolescents.  Am J Cardiol 1980, 46(3):429-438.
10.	 Silver, M. M. , et al.  Calcification in Porcine Xenograft Valves in Children.  Am J 
Cardiol 1980, 45:685-689.
11.	 Carpentier, A. , et al.  Continuing Improvements in Valvular Bioprostheses.  
J Thorac Cardiovasc Surg 1982, 83(1):27-42.
12.	 Bonow R. O. , et al.  ACC/AHA Guidelines for the Management of Patients with 
Valvular Heart Disease: A Report of the American College of Cardiology/
American Heart Association Task Force on Practice Guidelines (Committee 
on Management of Patients With Valvular Heart Disease).  J Am Coll Cardiol 
2006, 48:e1-148.
13.	 Moront, M. G.  and N. M.  Katz.  Early Degeneration of a Porcine Aortic Valve 
Bioprosthesis in the Mitral Valve Position in an Elderly Woman and its 
Association with Long-Term Calcium Carbonate Therapy.  Am J Cardiol 1987, 
59:1006-1007.
14.	 Aupart, M. R. , et al.  Perimount Pericardial Bioprosthesis for Aortic Calcified 
Stenosis: 18-Year Experience with 1,133 Patients.  J Heart Valve Dis 2006, 
15:768-776.
15.	 Dellgren, G. , et al.  Late Hemodynamic and Clinical Outcomes of Aortic Valve 
Replacement with the Carpentier-Edwards Perimount Pericardial 
Bioprosthesis.  J Thorac Cardiovasc Surg 2002, 124:146-154.
16.	 Frater, R. W. M. , et al.  Long-Term Durability and Patient Functional Status of 
the Carpentier-Edwards Perimount Pericardial Bioprosthesis in the Aortic 
Position.  J Heart Valve Dis 1998, 7:48-53.
17.	 Jamieson,W. R. E. , et al.  15-Year Comparison of Supra-Annular Porcine and 
PERIMOUNT Aortic Bioprostheses.  Asian Cardiovasc Thorac Ann 2006, 
14:200-205.
18.	 Borger, M. A. , et al.  Carpentier-Edwards Perimount Magna Valve Versus 
Medtronic Hancock II: A Matched Hemodynamic Comparison.  Ann Thorac 
Surg 2007; 83:2054-2058.
19.	 Botzenhardt, F. , et al.  Hemodynamic Comparison of Bioprostheses for 
Complete Supra-Annular Position in Patients With Small Aortic Annulus.  
J Am Coll Cardiol 2005, 45:2054-2060.
20.	 Botzenhardt, F. , et al.  Hemodynamic Performance and Incidence of 
Patient‑Prosthesis Mismatch of the Complete Supraanular 
Perimount Magna Bioprosthesis in the Aortic Position.  Thorac Cardiov Surg 
2005, 53:226-230.
21.	 Dalmau, M. J. , et al.  The Carpentier-Edwards Perimount Magna Aortic 
Xenograft: A New Design with an Improved Hemodynamic Performance.  
Interact Cardiovasc Thorac Surg 2006, 5:263-267.  
22.	 Totaro, P. , et al.  Carpentier-Edwards PERIMOUNT Magna Bioprosthesis: A 
Stented Valve with Stentless Performance? J Thorac Cardiovasc Surg 2005, 
130:1668-1674.
23.	 Wagner, I. M. , et al.  Influence of Completely Supra-annular Placement of 
Bioprostheses on Exercise Hemodynamics in Patients With a Small Aortic 
Annulus.  J Thorac Cardiovascular Surg 2007; 133:1234-1241.
This product is manufactured and distributed under at least one or more of the 
following U. S.  Patents: US-Patent Nos.  5,928,281; 5,931,969; 5,961,549; 
6,102,944; 6,245,105; 6,413,275; 6,561,970; 6,585,766; 6,837,902; 6,945,997; 
7,214,344; 7,972,376; 8,007,992; 8,357,387; 8,366,769; 8,632,608; and RE 40570; 
and corresponding foreign patents.  Likewise, additional patents pending.
Refer to the symbol legend at the end of this document.

10
Table 2. Summary of Complication Rates, Model 2700
Complication
Isolated AVR Population
DVR Population
Operative 
% of Pts.
Post- 
Operative  
% Per Pt. Yr.
% Event-Free  
at Six Years 
(Standard Error)
Operative 
% of Pts.
Post- 
Operative  
% Per Pt. Yr.
% Event-Free  
at Six Years 
(Standard Error)
Death
Explant
Valve Related Reoperation
All Reoperation
Valve Related Thromboembolism
All Thromboembolism
Endocarditis
Valve Dysfunction
Perivalvular Leak
Hemorrhagic Anticoagulation Complication
Hemolysis
Valve Thrombosis
4. 7
0
0. 7
22. 4
3. 1
5. 0
0. 6
0. 1
0. 1
1. 4
0
0
4. 6
0. 3
0. 1
1. 8
1. 5
2. 4
0. 8
0. 7
0. 3
0. 4
0. 2
0
73. 5 (2. 0)
98. 5 (1. 0)
99. 8 (0. 4)
75. 4 (1. 8)
91. 4 (1. 1)
84. 9 (1. 6)
95. 8 (0. 9)
96. 0 (1. 1)
98. 8 (0. 5)
96. 4 (1. 1)
99. 1 (0. 4)
100. 0 (0)
12. 9
0
0
34. 3
1. 4
5. 7
1. 4
0
0
4. 3
0
0
4. 2
0. 8
0
2. 3
5. 1
6. 6
1. 5
0. 4
1. 2
2. 3
0. 4
0. 4
67. 2 (6. 5)
NA *
NA *
NA *
NA *
NA *
NA *
NA *
NA *
NA *
NA *
NA *
* NA = Not Applicable
Table 3. Postoperative Echocardiography Results, Model 2700
Valve Size
19 mm
21 mm
23 mm
25 mm
27 mm
29 mm
Total
Total N
Avg.  Months Postoperative
Velocity (M/sec)
	 mean ± S. D.
	 n =
	 range
Peak Instantaneous 
Gradient (mmHg)
	 mean ± S. D.
	 n =
	 range
12
28. 6 ± 7. 2
2. 80 ± 0. 49
12
1. 90 - 3. 60
 
32. 22 ± 11. 08
12
14. 40 - 51. 80
22
34. 9 ± 8. 6
2. 56 ± 0. 46
21
1. 90 - 3. 90
 
27. 04 ± 10. 49
21
14. 40 - 60. 80
15
36. 9 ± 9. 2
2. 36 ± 0. 42
15
1. 39 - 2. 86
 
23. 00 ± 7. 30
15
7. 70 - 32. 70
8
39. 9 ± 7. 6
2. 15 ± 0. 56
7
1. 00 - 2. 60
 
19. 50 ± 8. 16
7
4. 00 - 27. 00
3
31. 4 ± 15. 9
2. 09 ± 0. 27
3
1. 90 - 2. 40
 
17. 60 ± 4. 70
3
14. 40 - 23. 00
3
15. 3 ± 12. 2
2. 08 ± 0. 1
3
2. 05 - 2. 10
 
14. 4 ± 0. 58
3
13. 95 - 15. 06
63
34. 6 ± 9. 2
2. 46 ± 0. 50
61
1. 00 - 3. 90
 
25. 67 ± 10. 14
61
4. 00 - 60. 80

11
Table 4. Effectiveness Outcomes, NYHA Functional Class, Model 2700
Preoperative  
NYHA Functional Class
Postoperative  
NYHA Functional Class
I
II
III
IV
Expiration
Not  
Available
I
II
III
IV
Not Available
18
140
181
43
5
19
37
48
16
1
4
2
1
9
35
72
53
2
15
24
2
2
Table 5. Freedom from Complication Rates at 20 years (N = 267), Model 2700
Freedom from Complications at 20 Years
Actual
Actuarial
Linearized (%/ptyr)
Valve-Related Expirations
Thromboembolism/Thrombosis
Bleeding
Endocarditis/Sepsis
Explant due to SVD
≥ 60
≥ 65
> 70
85. 8 ± 2. 5%
82. 4 ± 2. 6%
94. 0 ± 1. 5%
91. 7 ± 1. 7%
92. 6 ± 2. 0%
96. 3 ± 1. 6%
96. 0 ± 2. 3%
67. 9 ± 6. 6%
68. 2 ± 6. 8%
91. 7 ± 2. 2%
89. 3 ± 2. 4%
77. 1 ± 7. 2%
81. 5 ± 9. 6%
69. 9 ± 20. 5%
1. 2
1. 7
0. 4
0. 8
n. r. *
* Not relevant. SVD does not occur as a constant hazard function; consequently, linearized rates are not meaningful.
Table 6. Summary of Valve-Related Adverse Events, Models 3000 and 3000TFX
Adverse Events
≤ 30 Days Post-Operative
> 30 Days Post-Operative
3000TFX (N = 193) 
# of events (% of Pts)
3000/3000TFX  
(N = 253) 
# of events (% of Pts)
3000TFX (N = 193) 
# of events (% of Pts)
3000/3000TFX  
(N = 253) 
# of events (% of Pts)
Valve-Related Thromboembolism
Non-Structural Valve Dysfunction (PVL)
Explant (NSVD)
Death (Cardiac Arrest, Bleeding Event, CVA)
Reoperation
Hemolysis
AC related Bleeding
Endocarditis
Structural Valve Deterioration
Valve Thrombosis
Other (Tear In Aorta)
6 (3. 1)
3 (1. 5)
2 (1. 0)
1 (0. 5)
1 (0. 5)
1 (0. 5)
0 (0. 0)
0 (0. 0)
0 (0. 0)
0 (0. 0)
1 (0. 5)
7 (2. 8)
4 (1. 6)
2 (0. 8)
1 (0. 4)
1 (0. 4)
1 (0. 4)
0 (0. 0)
0 (0. 0)
0 (0. 0)
0 (0. 0)
1 (0. 4)
3 (2. 0)
3 (2. 0)
0 (0. 0)
3 (2. 0)
1 (0. 7)
3 (2. 0)
2 (1. 4)
0 (0. 0)
0 (0. 0)
0 (0. 0)
0 (0. 0)
3 (1. 4)
3 (1. 4)
0 (0. 0)
3 (1. 4)
1 (0. 5)
3 (1. 4)
2 (1. 0)
0 (0. 0)
0 (0. 0)
0 (0. 0)
0 (0. 0)

12
Table 7. Hemodynamic Variables at 1-Year Follow-Up Echo Assessment, Models 3000 and 3000TFX
Valve Type
Variable
19 mm 
Mean ± SD (N)
21 mm 
Mean ± SD (N)
23 mm 
Mean ± SD (N)
25 mm 
Mean ± SD (N)
27 mm 
Mean ± SD (N)
29 mm 
Mean ± SD (N)
3000TFX
Mean Systolic 
Gradient (mmHg)
16. 7 ± 4. 7  
(10)
15. 8 ± 4. 4  
(18)
11. 3 ± 3. 7  
(45)
11. 1 ± 4. 1  
(37)
9. 4 ± 4. 3  
(12)
9. 0 ± 0. 0  
(2)
Ejection  
Fraction (%)
65. 8 ± 10. 4  
(10)
62. 7 ± 9. 4  
(19)
60. 6 ± 11. 3  
(48)
61. 4 ± 11. 2  
(38)
59. 5 ± 10. 7  
(12)
55. 0 ±14. 1  
(2)
Aortic EOA  
(cm2)
1. 2 ± 0. 4  
(10)
1. 5 ± 0. 4  
(18)
1. 8 ± 0. 6  
(44)
1. 8 ± 0. 5  
(36)
2. 1 ± 0. 6  
(12)
2. 1 ± 0. 1  
(2)
3000/ 
3000TFX
Mean Systolic 
Gradient (mmHg)
16. 7 ± 4. 2  
(16)
13. 8 ± 4. 8  
(34)
11. 7 ± 4. 7  
(56)
11. 0 ± 3. 8  
(47)
9. 5 ± 4. 1  
(14)
9. 0 ± 0. 0  
(2)
Ejection  
Fraction (%)
62. 1 ± 15. 1  
(16)
58. 6 ± 11. 6  
(34)
60. 2 ± 11. 2  
(59)
60. 2 ± 11. 5  
(47)
58. 5 ± 10. 5  
(14)
55. 0 ± 14. 1  
(2)
Aortic EOA  
(cm2)
1. 3 ± 0. 5  
(16)
1. 5 ± 0. 4  
(32)
1. 8 ± 0. 6  
(55)
1. 8 ± 0. 6  
(46)
2. 1 ± 0. 6  
(14)
2. 1 ± 0. 1  
(2)
Table 8. NYHA Functional Class: Change From Baseline To 1-Year Visit, Models 3000 and 3000TFX
-----Baseline-----
Valve Type
Follow-Up NYHA Class
Class I
Class II
Class III
Class IV
N/A
3000TFX
N = 193
Class I
10
33
51
10
3
Class II
2
8
13
2
1
Class III
-
-
3
-
-
Class IV
-
-
-
1
-
Expiration
-
3
16
1
-
Explant
-
-
3
-
-
N/A
2
6
21
4
-
3000/ 
3000TFX
N = 253
Class I
12
40
71
11
3
Class II
2
14
29
3
1
Class III
-
-
3
-
-
Class IV
-
-
1
1
-
Expiration
-
3
19
2
-
Explant
-
-
3
-
-
N/A
2
7
22
4
-
NYHA Functional Class: Change From Baseline To 1-Year Visit
Valve Type
Improve 
N (%)
Same 
N (%)
Worse 
N (%)
N/A 
N (%)
3000TFX (N = 193)
109 (56. 5)
22 (11. 4)
2 (1. 0)
60 (31. 1)
3000/3000TFX (N = 253)
154 (60. 9)
30 (11. 9)
3 (1. 2)
66 (26. 1)

15
5.2	 Événements indésirables potentiels
Les événements indésirables potentiels associés à l’utilisation de biovalvules 
cardiaques prothétiques sont les suivants :
• 
Angine de poitrine
• 
Diathèse hémorragique (coagulopathie) en lien avec l’anticoagulothérapie
• 
Arythmie cardiaque
• 
Blocage de la valvule ostiale coronaire
• 
Endocardite
• 
Insuffisance cardiaque
• 
Hémolyse
• 
Anémie hémolytique
• 
Hémorragie
• 
Infection locale et systémique
• 
Infarctus du myocarde
• 
Inadaptation de la prothèse au patient 
• 
Enclavement de la valve prothétique (coincement)
• 
Dysfonction non structurelle de la prothèse
• 
Pannus de la prothèse
• 
Fuite périvalvulaire de la prothèse
• 
Régurgitation de la prothèse
• 
Détérioration de la structure de la prothèse
• 
Thrombose prothétique
• 
Accident vasculaire cérébral
• 
Thrombo-embolie
• 
Insuffisance cardiaque congestive
Ces complications peuvent avoir les conséquences suivantes :
 
• 
Nouvelle opération chirurgicale
 
• 
Explantation
 
• 
Handicap permanent
 
• 
Décès
6.	 Études cliniques 
Cohorte de patients avec approbation préalable
Des données cliniques sur 719 patients ayant besoin isolément d’un remplacement 
de la valvule aortique (RVA) par la bioprothèse péricardique PERIMOUNT de 
Carpentier-Edwards, modèle 2700, avec suivi moyen de 3,9 années, indiquent un 
taux de survie global (calcul actuariel) de 73,7 % ± 2 % à la 6e année.  Les données 
cliniques provenant de 70 patients ayant besoin d’un remplacement double de la 
valvule (RDV) avec suivi moyen de 3,7 années, indiquent un taux de survie global 
(calcul actuariel) de 67,2 % ± 6,5 % à la 6e année.  Ces données sur une cohorte de 
patients avec approbation préalable ont été recueillies dans la période allant 
d’août 1981 à janvier 1989.  
La population ayant subi isolément un RVA comprenait un total de 455 hommes 
(63,3 %) et de 264 femmes (36,7 %).  Leur âge moyen (± l’écart-type) au moment 
de l’implantation était de 64 ans (± 12,4), et ils étaient âgés de 18 à 90 ans.  Les 
indications pour le remplacement de la valvule étaient la sténose (63,4 %), la 
régurgitation (16,3 %), des maladies mixes (15,3 %) et une dysfonction de la 
valvule aortique prothétique (5 %).  
La population ayant subi un RDV comprenait un total de 24 hommes (34,3 %) et 
de 46 femmes (65,7 %).  L’âge moyen (± l’écart-type) était de 62,9 ans (± 12,7), 
et ils étaient âgés de 31 à 94 ans.  Les indications pour le remplacement de la 
valvule étaient la sténose (45,7 %), la régurgitation (25,7 %), des maladies 
mixes (21,4 %) et une dysfonction de la valvule aortique prothétique (7,4 %).
Les méthodes de suivi incluaient des visites à l’hôpital, des visites au cabinet et 
des communications par téléphone ou par lettre avec le patient, sa famille ou le 
médecin.
Le tableau 2 récapitule les taux de complications opératoires et postopératoires 
pour la population avec RVA isolé et pour la population ayant subi un RDV.  Les 
taux de complications opératoires proviennent de 719 patients de la population 
ayant subi un RVA isolé et de 70 patients de la population ayant subi un RDV.  
Les taux de complications postopératoires se basent sur un suivi de 2767,9 et 
255,8 années ayant eu lieu plus de 30 jours après les implantations chez la 
population ayant subi un RVA isolé et chez la population ayant subi un RDV, 
respectivement.
Le tableau 3 présente les résultats de l’échocardiographie postopératoire des 
patients de la population de cette étude, par taille de valvule.
Les données sur la classification fonctionnelle préopératoire et postopératoire de 
la NYHA ont été recueillies pour la population ayant subi isolément un RVA.  La 
classification fonctionnelle de la NYHA n’a pas été mentionnée pour 220 patients 
(171 patients décédés et 49 patients non disponibles).  En ce qui concerne les 
499 patients pour lesquels la classification fonctionnelle préopératoire et 
postopératoire de la NYHA a été mentionnée lors du dernier suivi disponible, la 
situation s’était empirée pour 10 d’entre eux (2 %), était inchangée pour 
59 d’entre eux (11,8 %) et s’était améliorée pour 430 d’entre eux (86,2 %).
Le tableau 4 présente une comparaison des données de la classification 
fonctionnelle préopératoire de la NYHA avec celles de la classification 
postopératoire lors du dernier suivi.
Cohorte de patients avec approbation postérieure
Depuis novembre 1981, Edwards a suivi une cohorte approuvée 
postérieurement de 267 patients ayant subi un remplacement de la valvule 
(RVA) (modèle 2700), provenant de quatre centres de l’étude clinique d’origine 
de la bioprothèse péricardique PERIMOUNT de Carpentier-Edwards.  Cette 
population était constituée de 171 hommes (64 %) et de 96 femmes (36 %).  
Leur âge moyen (± écart-type) au moment de l’implantation était de 64,9 ans 
± 11,8 ans, et ils étaient âgés de 21 à 86 ans.  En tout, 2407 années-patient de 
données étaient disponibles pour l’analyse (2386 d’années-patient tardives).  Le 
suivi moyen était de 9 ± 5,5 ans, avec un maximum de 20,3 ans.  En tout, on 
compte 189 décès entre 1981 et 1994, dont 48 (25,3 %) en lien établi avec la 
valvule.  Les méthodes de suivi utilisées par chaque clinique incluaient des visites 
à l’hôpital, des visites au cabinet et des communications par téléphone ou par 
lettre avec le patient, sa famille ou le médecin.  
Le tableau 5 résume la latitude découlant des taux de complications après 
20 ans.  La situation des patients à partir du dernier intervalle de suivi incluait 
189 décédés (70,8 %), 10 vivants (3,8 %), 46 ayant subi une explantation 
(17,2 %) et 22 ayant quitté le suivi (8,2 %).  
Cette population comptait 48 décès en lien avec la valvule.  Un décès en lien avec 
la valvule est survenu au cours de la période de l’opération, par saignement.  Sur 
les 28 décès postopératoires en lien avec la valvule, 5 découlaient de thrombo-
embolie, 4 d’endocardite/sepsie, 3 de détérioration de la structure de la valvule 
et 1 de saignement.  Quinze autres décès ont été associés à la valvule à cause du 
manque d’information, ou parce qu’ils ont été classés ainsi par le chercheur.  Le 
calcul actuariel de la latitude des décès liés à la valvule donne 67,9 ± 6,6 % 
après 20 ans.  Enfin, 19 autres décès sont reliés à une cause inconnue ou à une 

16
mort subite, et pourraient avoir un lien avec la valvule.  Par prudence, ces décès 
sont associés à la valvule.  Par conséquent, la latitude actuarielle qui en découle 
pour les décès en lien avec la valvule sont de 55,4 ± 6,4 % après 20 ans.  
Une amélioration dans la classification fonctionnelle de la NYHA a également été 
démontrée dans la période postopératoire.  Jusqu’à l’évaluation du dernier suivi, 
108 patients (44,8 %) faisaient partie de la classe fonctionnelle I de la NYHA.  
Ces données sont été compilées à partir d’un essai clinique multicentre effectué 
par Edwards Lifesciences.  Pour en savoir plus sur cet essai, communiquez avec 
Edwards Lifesciences S. A. R. L. , Heart Valve Therapy Marketing Department, One 
Edwards Way, Irvine, CA 92614-5686.
Étude de confirmation
Entre les mois d’août 2003 et janvier 2004, 60 patients ayant besoin d’un 
remplacement de la valvule aortique (RVA) se sont vus implanter la bioprothèse 
aortique Magna PERIMOUNT de Carpentier-Edwards (modèle 3000) dans cinq 
établissements (deux en Europe et trois au Canada).  Peu de temps après, le 
protocole a été modifié en vue d’autoriser l’implantation de la bioprothèse 
aortique Magna PERIMOUNT de Carpentier-Edwards (modèle 3000TFX), et 
d’ajouter trois établissements américains.  Par la suite, 193 autres patients se 
sont vus implanter le modèle 3000TFX entre décembre 2004 et décembre 2006.  
À la différence du modèle 3000, le modèle 3000TFX est traité par le biais du 
processus ThermaFix.
La population ayant reçu le modèle 3000TFX comprenait un total de 116 hommes 
(60,1 %) et de 77 femmes (39,9 %).  L’âge moyen au moment de l’implantation 
était de 72 ans (écart-type de ± 8,59) et ils étaient âgés de 26 à 89 ans.  La 
principale indication pour le remplacement de la valvule était la sténose (78,2 %), 
suivie des maladies mixtes (14,5 %) et de la régurgitation (7,3 %).
La population ayant reçu les modèles 3000 et 3000TFX comprenait un total de 
150 hommes (59,3 %) et de 103 femmes (40,7 %).  L’âge moyen au moment de 
l’implantation était de 72,2 ans (écart-type de ± 8,31) et ils étaient âgés de 26 à 
89 ans.  Ici encore, la principale indication pour le remplacement de la valvule 
était la sténose (77,5 %), suivie des maladies mixtes (15,4 %) et de la 
régurgitation (7,1 %).
Les patients étaient évalués avant l’opération, pendant l’opération, lors de la sortie, 
entre 3 et 6 mois, après un an, et chaque année par la suite.  Le suivi cumulatif pour 
le modèle 3000TFX était de 167 années-patient, pour un suivi moyen de 0,9 année 
(écart-type = 0,42, plage = 0 à 2,1 années).  Le suivi cumulatif pour les modèles 
3000 et 3000TFX combinés était de 232 années-patient, avec un suivi moyen de 
0,9 année (écart-type = 0,42, plage = 0 à 2,1 années).  
Le tableau 6 récapitule les taux d’événements indésirables en lien avec la 
valvule et survenus au début (≤ 30 jours) et à la fin (> 30 jours) de la période 
postopératoire dans les populations ayant reçu le modèle 3000TFX et les 
modèles 3000 et 3000TFX combinés, respectivement.
Le tableau 7 illustre, par taille de valvule, les variables hémodynamiques 
signalées dans les échocardiogrammes effectués après un an chez les patients 
des études sur le modèle 3000TFX et sur les modèles 3000 et 3000TFX combinés.
Le tableau 8 présente le changement de classe fonctionnelle de la NYHA par 
rapport à l’évaluation de base de la visite après un an.  Il convient de remarquer 
qu’une amélioration de 56,5 % a été signalée lors de la visite de un an dans la 
classification fonctionnelle de la population portant le modèle 3000TFX.  En ce 
qui concerne les modèles 3000 et 3000TFX combinés, on constate une 
amélioration de 60,9 % dans la classification fonctionnelle au bout d’un an.
Plusieurs études cliniques ayant été publiées démontrent la durabilité à long 
terme des bioprothèses aortiques péricardiques PERIMOUNT de 
Carpentier‑Edwards, qui constituent la base sur laquelle les bioprothèses 
aortiques péricardiques Magna et Magna Ease PERIMOUNT de 
Carpentier‑Edwards sont conçues (réfs.  14, 15, 16 & 17).  De plus, des données 
publiées prouvent que la bioprothèse aortique Magna PERIMOUNT a un 
rendement hémodynamique exceptionnel et ne présente qu’un risque très 
réduit d’inadaptation de la prothèse au patient (réfs.  18, 19, 20, 21, 22 & 23).
7.	 Individualisation du traitement
Sauf indication contraire, les destinataires de la valvule bioprothétique doivent 
suivre une anticoagulothérapie pendant les premiers stades suivant 
l’implantation, selon les consignes données à chacun par le médecin.  Une 
anticoagulothérapie ou un traitement antiplaquettaire doit être envisagé pour 
les patients montrant des facteurs de risque de thrombo-embolie.  
Le jugement final concernant les soins pour un patient donné doit être pris par 
le fournisseur de santé et le patient à la lumière de l’ensemble de la situation 
que présente ce dernier (réf.  12).  Il est recommandé de poser une bioprothèse 
en cas de RVA sur des patients de tous âges qui ne prennent pas de warfarine ou 
pour lesquels il existe une contre-indication importante à la thérapie à base de 
warfarine.  Les préférences du patient sont également à prendre en compte dans 
une mesure raisonnable lors du choix de l’opération de la valvule aortique et de 
la valve prothétique.  Il est raisonnable d’envisager l’implantation d’une 
prothèse mécanique pour un RVA de patients de moins de 65 ans pour lesquels 
l’anticoagulation n’est pas contre-indiquée.  Il est également raisonnable 
d’envisager l’implantation d’une bioprothèse pour un RVA de patients de moins 
de 65 ans qui ont fait ce choix pour des raisons de mode de vie après avoir été 
informés dans les détails des risques de l’anticoagulation par rapport à 
l’éventuelle nécessité d’un deuxième RVA (réf.  12).
7.1	 Populations de patients spécifiques
L’innocuité et l’efficacité de la bioprothèse 11000A n’ont pas été établies pour 
les populations suivantes, sur lesquelles elles n’ont pas été étudiées :
 
• 
patientes enceintes ;
 
• 
mères qui allaitent ;
 
• 
patients métabolisant le calcium de manière anormale (p. ex., 
insuffisance rénale, hyperparathyroïdisme) ;
 
• 
patients présentant une insuffisance dégénérative anévrismale de 
l’aorte (p.  ex. , nécrose médiale kystique, syndrome de Marfan) ;
 
• 
enfants, adolescents et jeunes adultes.
Avertissement : selon des rapports issus de documentation sur des valvules 
tissulaires (réfs.  6, 7, 8, 9 et 10), la fréquence des calcifications de la valve serait 
supérieure chez les patients de moins de 20 ans.  Lorsque cela est possible, il faut 
éviter les injections intraveineuses répétées contenant du calcium pendant la 
période postopératoire.  Parallèlement, la consommation excessive de lait ou de 
produits laitiers doit être évitée chez l’enfant.  À cet égard, les recherches 
effectuées sur les animaux (réf.  11) démontrent qu’un niveau élevé de calcium 
dans le système peut entraîner une calcification précoce.
8.	 Informations et conseils au patient
Il est conseillé de procéder à un suivi sérieux et continu (au moins par une visite 
annuelle chez le médecin) afin que les complications liées à la bioprothèse, et 
plus particulièrement aux problèmes de matériau, puissent faire l’objet d’un 
diagnostic et d’un traitement adaptés.  Les patients porteurs de bioprothèses 
sont vulnérables à la bactériémie (p.  ex. , lors de procédures dentaires) et doivent 
recevoir des conseils concernant l’antibioprophylaxie.  Enfin, il faut encourager 
les patients à porter en permanence leur carte d’identification et d’informer les 
fournisseurs dont ils sollicitent des soins qu’ils possèdent un implant.
9.	 Présentation
9.1 	 Conditionnement
La bioprothèse aortique péricardique d’Edwards, modèle 11000A, est fournie 
stérile et non pyrogène.  Elle est livrée dans un emballage de plateau à double 
barrière placé dans un sachet métallisé, se trouvant lui-même dans un carton.

17
Chaque bioprothèse se trouve dans un carton avec un indicateur de température 
visible à travers une fenêtre sur le panneau latéral.  Cet indicateur vise à repérer 
les produits exposés à des températures extrêmes transitoires.  À la réception de 
la bioprothèse, inspecter immédiatement l’indicateur et consulter l’étiquette du 
carton pour confirmer l’état « Utiliser ».  Si l’état « Utiliser » n’est pas apparent, 
ne pas se servir de la bioprothèse et contacter le fournisseur local ou le 
représentant d’Edwards Lifesciences pour prendre des arrangements en vue 
d’une autorisation de retour et d’un remplacement.  
Mise en garde : inspecter soigneusement la bioprothèse avant 
l’implantation pour trouver des traces d’exposition à des températures 
extrêmes ou d’autres dégâts.
9.2	 Stockage
La bioprothèse aortique péricardique d’Edwards, modèle 11000A, doit être 
entreposée à une température comprise entre 10 °C et 25 °C (50 °F et 77 °F), 
dans son sachet métallisé et son carton de rangement.
10.	 Directives d’utilisation
10.1	 Formation du médecin
Les techniques d’implantation de cette bioprothèse sont semblables à celles du 
placement supra-annulaire de n’importe quelle bioprothèse aortique avec 
endoprothèse.  Aucune formation particulière n’est nécessaire pour implanter la 
bioprothèse aortique péricardique d’Edwards, modèle 11000A.
10.2	 Choix de la taille
Vérifier que les accessoires ont été stérilisés conformément aux 
recommandations fournies avec les articles réutilisables.
Mesure supra-annulaire
Pour l’implantation supra-annulaire, l’anneau de suture de la bioprothèse est 
placé au-dessus de l’annulus, maximisant ainsi la zone de l’orifice de la valve.  
Lors de la mesure pour une implantation supra-annulaire, le calibreur doit être 
placé parallèlement au plan de l’annulus et il faut utiliser la technique de 
mesure suivante :
Étape
Procédure
1
À l’aide du calibreur de modèle 1133, sélectionner l’embout 
cylindrique du calibreur ayant le diamètre le plus large qui 
s’adapte confortablement dans l’annulus du patient.
HVT21
Étape
Procédure
2
Une fois que l’embout cylindrique approprié a été vérifié, 
utiliser l’embout de réplique du même calibreur afin de vérifier 
que l’anneau de suture s’adapte bien sur le dessus de l’annulus.  
S’assurer que l’ostium coronaire n’est pas bloqué et que les 
montants de l’endoprothèse du bout de réplique n’interfèrent 
pas avec la paroi aortique à la jonction sinotubulaire.  Si 
l’embout de réplique convient, choisir cette taille de 
bioprothèse pour l’implantation.
HVT37
10.3	 Instructions de manipulation et de préparation
Il est conseillé de suivre une formation sur le tas avant de manipuler et de 
préparer la bioprothèse aortique péricardique d’Edwards, modèle 11000A.
Étape
Procédure
1
Avertissement : ne pas ouvrir pas l’emballage du 
modèle 11000A de la bioprothèse aortique péricardique 
d’Edwards avant d’avoir l’assurance que l’implantation 
aura lieu.
Mise en garde : Ne pas ouvrir le sachet métallisé dans une 
zone stérile. Ce sachet ne sert qu’à protéger la 
bioprothèse. Seul l’emballage le plus à l’intérieur peut 
pénétrer dans la zone stérile.
Une fois que la bonne taille de bioprothèse a été choisie, retirer le 
sachet métallisé du carton dans la zone non stérile.  Avant 
d’ouvrir, examiner l’emballage pour vérifier s’il y a des 
dommages et des scellés cassés ou manquants.
2
Près de la zone stérile, tenir la base du plateau extérieur et retirer 
son couvercle.

22
16.	 Frater, R. W. M. , et al.  Long-Term Durability and Patient Functional Status of 
the Carpentier-Edwards Perimount Pericardial Bioprosthesis in the Aortic 
Position.  J Heart Valve Dis 1998, 7:48-53.
17.	 Jamieson,W. R. E. , et al.  15-Year Comparison of Supra-Annular Porcine and 
PERIMOUNT Aortic Bioprostheses.  Asian Cardiovasc Thorac Ann 2006, 
14:200-205.
18.	 Borger, M. A. , et al.  Carpentier-Edwards Perimount Magna Valve Versus 
Medtronic Hancock II: A Matched Hemodynamic Comparison.  Ann Thorac 
Surg 2007; 83:2054-2058.
19.	 Botzenhardt, F. , et al.  Hemodynamic Comparison of Bioprostheses for 
Complete Supra-Annular Position in Patients With Small Aortic Annulus.  
J Am Coll Cardiol 2005, 45:2054-2060.
20.	 Botzenhardt, F. , et al.  Hemodynamic Performance and Incidence of 
Patient‑Prosthesis Mismatch of the Complete Supraanular 
Perimount Magna Bioprosthesis in the Aortic Position.  Thorac Cardiov Surg 
2005, 53:226-230.
21.	 Dalmau, M. J. , et al.  The Carpentier-Edwards Perimount Magna Aortic 
Xenograft: A New Design with an Improved Hemodynamic Performance.  
Interact Cardiovasc Thorac Surg 2006, 5:263-267.  
22.	 Totaro, P. , et al.  Carpentier-Edwards PERIMOUNT Magna Bioprosthesis: A 
Stented Valve with Stentless Performance? J Thorac Cardiovasc Surg 2005, 
130:1668-1674.
23.	 Wagner, I. M. , et al.  Influence of Completely Supra-annular Placement of 
Bioprostheses on Exercise Hemodynamics in Patients With a Small Aortic 
Annulus.  J Thorac Cardiovascular Surg 2007; 133:1234-1241.
Ce produit est fabriqué et distribué selon au moins un des brevets américains 
suivants : Nos de brevets américains 5,928,281; 5,931,969; 5,961,549; 
6,102,944; 6,245,105; 6,413,275; 6,561,970; 6,585,766; 6,837,902; 6,945,997; 
7,214,344; 7,972,376; 8,007,992; 8,357,387; 8,366,769; 8,632,608; et RE 40570; 
ainsi que les brevets étrangers correspondants.  De plus, des brevets 
supplémentaires sont en attente.
Se référer à la légende des symboles à la fin du document.

23
Tableau 2 - Récapitulation des taux de complications, modèle 2700
Complication
Population ayant subi isolémentun RVA
Population ayant subi un RDV
Opératoires 
% de pt
Post 
Opératoires 
% par année-
patient
% sans  
événement  
après 6 ans 
(écart-type)
Opératoires 
% de pt
Post 
Opératoires 
% par année-
patient
% sans  
événement  
après 6 ans 
(écart-type)
Décès
Explantation
Nouvelle opération en lien avec la valvule
Toutes les nouvelles opérations
Thrombo-embolie en lien avec la valvule
Toutes les thrombo-embolies
Endocardite
Dysfonction de la valvule
Fuite périvalvulaire
Complication hémorragique anticoagulation
Hémolyse
Thrombose de la valvule
4,7
0
0,7
22,4
3,1
5,0
0,6
0,1
0,1
1,4
0
0
4,6
0,3
0,1
1,8
1,5
2,4
0,8
0,7
0,3
0,4
0,2
0
73,5 (2,0)
98,5 (1,0)
99,8 (0,4)
75,4 (1,8)
91,4 (1,1)
84,9 (1,6)
95,8 (0,9)
96,0 (1,1)
98,8 (0,5)
96,4 (1,1)
99,1 (0,4)
100,0 (0)
12,9
0
0
34,3
1,4
5,7
1,4
0
0
4,3
0
0
4,2
0,8
0
2,3
5,1
6,6
1,5
0,4
1,2
2,3
0,4
0,4
67,2 (6,5)
S. O. *
S. O. *
S. O. *
S. O. *
S. O. *
S. O. *
S. O. *
S. O. *
S. O. *
S. O. *
S. O. *
* S. O.  = sans objet
Tableau 3 - Résultats de l’échocardiographie postopératoire, modèle 2700
Taille de la valvule
19 mm
21 mm
23 mm
25 mm
27 mm
29 mm
Total
Total N
Moyenne des mois 
après l’opération
Vélocité (M/s)
	 moyen ± E. -T.
	 n =
	 Plage
Gradient instantané 
de crête (mmHg) 
	 moyen ± E. -T.
	 n =
	 Plage
12
 
28,6 ± 7,2
2,80 ± 0,49
12
1,90 - 3,60
 
32,22 ± 11,08
12
14,40 - 51,80
22
 
34,9 ± 8,6
2,56 ± 0,46
21
1,90 - 3,90
 
27,04 ± 10,49
21
14,40 - 60,80
15
 
36,9 ± 9,2
2,36 ± 0,42
15
1,39 - 2,86
 
23,00 ± 7,30
15
7,70 - 32,70
8
 
39,9 ± 7,6
2,15 ± 0,56
7
1,00 - 2,60
 
19,50 ± 8,16
7
4,00 - 27,00
3
 
31,4 ± 15,9
2,09 ± 0,27
3
1,90 - 2,40
 
17,60 ± 4,70
3
14,40 - 23,00
3
 
15,3 ± 12,2
2,08 ± 0,1
3
2,05 - 2,10
 
14,4 ± 0,58
3
13,95 - 15,06
63
 
34,6 ± 9,2
2,46 ± 0,50
61
1,00 - 3,90
 
25,67 ± 10,14
61
4,00 - 60,80

24
Tableau 4 - Résultats en matière d’efficacité, classification fonctionnelle de la NYHA, modèle 2700
Préopératoire Classification 
fonctionnelle de la NYHA
postopératoire 
Classification fonctionnelle de la NYHA
I
II
III
IV
Décès
Non disponible
I
II
III
IV
Non disponible
18
140
181
43
5
19
37
48
16
1
4
2
1
9
35
72
53
2
15
24
2
2
Tableau 5 - Latitude concernant les taux de complications après 20 ans (N = 267), modèle 2700
Latitude concernant les taux de 
complications après 20 ans
Réelle
Actuarielle
Linéarisée  
(%/année-patient)
Décès en lien avec la valvule
Thrombo-embolie/thrombose
Saignement
Endocardite/sepsie
Explantation due à une DSV
≥ 60
≥ 65
> 70
85,8 ± 2,5%
82,4 ± 2,6%
94,0 ± 1,5%
91,7 ± 1,7%
92,6 ± 2,0%
96,3 ± 1,6%
96,0 ± 2,3%
67,9 ± 6,6%
68,2 ± 6,8%
91,7 ± 2,2%
89,3 ± 2,4%
77,1 ± 7,2%
81,5 ± 9,6%
69,9 ± 20,5%
1,2
1,7
0,4
0,8
n. p. *
* Non pertinent. La DSV ne relève pas d’une fonction de risque constante. Par conséquent, les taux linéarisés ne sont pas significatifs.
Tableau 6 - Résumé des événements indésirables en lien avec la valvule, modèles 3000 et 3000TFX
Événements indésirables
≤ 30 jours après l’opération
> 30 jours après l’opération
3000TFX  
(N = 193) 
Nbre d’événements  
(% de patients)
3000/3000TFX  
(N = 253) 
Nbre d’événements  
(% de patients)
3000TFX  
(N = 193) 
Nbre d’événements  
(% de patients)
3000/3000TFX  
(N = 253) 
Nbre d’événements  
(% de patients)
Thrombo-embolies en lien avec la valvule
Dysfonction non structurelle de la valvule (PVL)
Explantation (DNSV)
Décès (arrêt cardiaque, saignement, AVC)
Nouvelle opération chirurgicale
Hémolyse
Saignement en lien avec l’AC
Endocardite
Détérioration de la structure de la valvule
Thrombose de la valvule
Autre (déchirure de l’aorte)
6 (3,1)
3 (1,5)
2 (1,0)
1 (0,5)
1 (0,5)
1 (0,5)
0 (0,0)
0 (0,0)
0 (0,0)
0 (0,0)
1 (0,5)
7 (2,8)
4 (1,6)
2 (0,8)
1 (0,4)
1 (0,4)
1 (0,4)
0 (0,0)
0 (0,0)
0 (0,0)
0 (0,0)
1 (0,4)
3 (2,0)
3 (2,0)
0 (0,0)
3 (2,0)
1 (0,7)
3 (2,0)
2 (1,4)
0 (0,0)
0 (0,0)
0 (0,0)
0 (0,0)
3 (1,4)
3 (1,4)
0 (0,0)
3 (1,4)
1 (0,5)
3 (1,4)
2 (1,0)
0 (0,0)
0 (0,0)
0 (0,0)
0 (0,0)

25
Tableau 7 - Variables hémodynamiques à l’évaluation échographique du suivi d’un an, modèles 3000 et 3000TFX
Type de valvule
Variable
19 mm 
Moyenne ±  
écart-type (N)
21 mm 
Moyenne ±  
écart-type (N)
23 mm 
Moyenne ±  
écart-type (N)
25 mm 
Moyenne ±  
écart-type (N)
27 mm 
Moyenne ±  
écart-type (N)
29 mm 
Moyenne ±  
écart-type (N)
3000TFX
Gradient systolique  
moyen (mmHg)
16,7 ± 4,7  
(10)
15,8 ± 4,4  
(18)
11,3 ± 3,7  
(45)
11,1 ± 4,1  
(37)
9,4 ± 4,3  
(12)
9,0 ± 0,0  
(2)
Fraction  
d’éjection (%)
65,8 ± 10,4  
(10)
62,7 ± 9,4  
(19)
60,6 ± 11,3  
(48)
61,4 ± 11,2  
(38)
59,5 ± 10,7  
(12)
55,0 ±14,1  
(2)
Aire valvulaire efficace  
de l’aorte (cm2)
1,2 ± 0,4  
(10)
1,5 ± 0,4  
(18)
1,8 ± 0,6  
(44)
1,8 ± 0,5  
(36)
2,1 ± 0,6  
(12)
2,1 ± 0,1  
(2)
3000/ 
3000TFX
Gradient systolique  
moyen (mmHg)
16,7 ± 4,2  
(16)
13,8 ± 4,8  
(34)
11,7 ± 4,7  
(56)
11,0 ± 3,8  
(47)
9,5 ± 4,1  
(14)
9,0 ± 0,0  
(2)
Fraction  
d’éjection (%)
62,1 ± 15,1  
(16)
58,6 ± 11,6  
(34)
60,2 ± 11,2  
(59)
60,2 ± 11,5  
(47)
58,5 ± 10,5  
(14)
55,0 ± 14,1  
(2)
Aire valvulaire efficace  
de l’aorte (cm2)
1,3 ± 0,5  
(16)
1,5 ± 0,4  
(32)
1,8 ± 0,6  
(55)
1,8 ± 0,6  
(46)
2,1 ± 0,6  
(14)
2,1 ± 0,1  
(2)
Tableau 8 - Classe fonctionnelle de la NYHA : changement par rapport à l’évaluation de base lors de la visite de un an, modèles 3000 et 3000TFX
-----Évaluation de base-----
Type de valvule
Suivi de la  
classification NYHA
Classe I
Classe II
Classe III
Classe IV
S.O.
3000TFX
N = 193
Classe I
10
33
51
10
3
Classe II
2
8
13
2
1
Classe III
-
-
3
-
-
Classe IV
-
-
-
1
-
Décès
-
3
16
1
-
Explantation
-
-
3
-
-
S.O.
2
6
21
4
-
3000/ 
3000TFX
N = 253
Classe I
12
40
71
11
3
Classe II
2
14
29
3
1
Classe III
-
-
3
-
-
Classe IV
-
-
1
1
-
Décès
-
3
19
2
-
Explantation
-
-
3
-
-
S.O.
2
7
22
4
-
Classe de fonctionnement de la NYHA : changement par rapport à l’évaluation de base lors de la visite de un an
Type de valvule
Amélioration 
N (%)
Identique 
N (%)
Aggravation 
N (%)
S.O. 
N (%)
3000TFX (N = 193)
109 (56,5)
22 (11,4)
2 (1,0)
60 (31,1)
3000/3000TFX (N = 253)
154 (60,9)
30 (11,9)
3 (1,2)
66 (26,1)

28
• 
Zablokowanie ujścia wieńcowego
• 
Zapalenie wsierdzia
• 
Niewydolność serca
• 
Hemoliza
• 
Niedokrwistość hemolityczna
• 
Krwotok
• 
Miejscowe i/lub uogólnione zakażenie
• 
Zawał mięśnia sercowego
• 
Niedopasowanie protezy do pacjenta (PPM) 
• 
Usidlenie płatka zastawki (wklinowanie)
• 
Niestrukturalna dysfunkcja protezy
• 
Wytworzenie łuszczki
• 
Przeciek okołozastawkowy
• 
Niedomykalność protezy
• 
Strukturalne uszkodzenie protezy
• 
Zakrzepica protezy
• 
Udar mózgu
• 
Zaburzenia zakrzepowo-zatorowe
• 
Przemijające niedokrwienie mózgu (TIA)
Wymienione powikłania mogą prowadzić do:
• 
powtórnego zabiegu operacyjnego
• 
usunięcia zastawki
• 
trwałej niepełnosprawności
• 
zgonu
6.	 Badania kliniczne 
Kohorta pacjentów przed zatwierdzeniem produktu
Dostępne dane kliniczne 719 pacjentów wymagających operacji wymiany jednej 
zastawki aortalnej (aortic valve replacement, AVR) na model bioprotezy 
osierdziowej 2700 Carpentier-Edwards PERIMOUNT, ze średnim okresem 
obserwacji wynoszącym 3,9 roku, wskazują na ogólny aktuarialny wskaźnik 
przeżycia 73,7% ± 2,0% w okresie 6 lat.  Dostępne dane kliniczne 70 pacjentów 
wymagających operacji wymiany dwóch zastawek (double valve replacement, 
DVR), ze średnim okresem obserwacji wynoszącym 3,7 roku, wskazują na ogólny 
aktuarialny wskaźnik przeżycia 67,2% ± 6,5% w okresie 6 lat.  Te dane dla grupy 
kontrolnej pacjentów przed zatwierdzeniem produktu zgromadzono w okresie 
od sierpnia 1981 do stycznia 1989 roku.  
W populacji wymagającej pojedynczego zabiegu AVR znajdowało się ogółem 
455 mężczyzn (63,3%) i 264 kobiety (36,7%), zaś średni wiek pacjentów 
podczas wszczepienia (± odchylenie standardowe) wynosił 64 lata (± 12,4) 
przy zakresie wieku od 18 do 90 lat.  Wskazaniami do wymiany zastawki były 
zwężenie (63,4%), niedomykalność (16,3%), wada mieszana (15,3%) oraz 
dysfunkcja poprzedniej prostetycznej zastawki aortalnej (5,0%).  
W populacji wymagającej zabiegu DVR znajdowało się ogółem 24 mężczyzn 
(34,3%) i 46 kobiet (65,7%), zaś średni wiek pacjentów podczas wszczepienia 
(± odchylenie standardowe) wynosił 62,9 lat (± 12,7) przy zakresie wieku od 
31 do 94 lat.  Wskazaniami do wymiany zastawki były: zwężenie (45,7%), 
niedomykalność (25,7%), wada mieszana (21,4%) oraz dysfunkcja poprzedniej 
protezy zastawki aorty (7,4%).
Metody obserwacji obejmowały wizyty w szpitalu, wizyty w gabinetach oraz 
kontakt telefoniczny lub listowny z pacjentem, jego rodziną lub miejscowym 
lekarzem.
Tabela 2 zawiera zestawienie współczynników powikłań operacyjnych i 
pooperacyjnych dla izolowanych populacji AVR i DVR.  Obliczenia wskaźników z 
okresu operacji oparto na grupie 719 pacjentów przechodzących zabieg AVR i 
70 pacjentów w grupie poddanej zabiegowi DVR.  Wskaźniki pooperacyjne 
obliczono na podstawie obserwacji wynoszącej 2767,9 i 255,8 pacjentolat, 
odpowiednio dla grup poddanych zabiegom AVR i DVR, mającej miejsce > 30 
dni po implantacji.
Tabela 3 przedstawia, według rozmiaru zastawki, wyniki echokardiografii w 
okresie pooperacyjnym dla tej populacji badania.
Zebrano informacje dotyczące przynależności pacjentów poddanych zabiegowi 
izolowanej AVR do poszczególnych klas czynnościowych NYHA przed i po 
operacji.  Klasy czynnościowej NYHA nie podawano w przypadku 220 pacjentów 
(171 pacjentów zmarło, a 49 pacjentów nie było dostępnych).  Spośród 
499 pacjentów, u których podano klasę czynnościową NYHA przed i po operacji 
(z ostatniej dostępnej wizyty kontrolnej), 10 pacjentów (2,0%) wykazywało 
pogorszenie, stan 59 pacjentów (11,8%) pozostawał bez zmian, zaś u 
430 pacjentów (86,2%) stwierdzono poprawę.
W tabeli 4 przedstawiono dane wynikające z porównania klasy czynnościowej 
NYHA sprzed operacji i po operacji z ostatniej wizyty kontrolnej.
Kohorta pacjentów po zatwierdzeniu produktu
Firma Edwards od listopada 1981 r.  kontynuuje badania kontrolne zatwierdzonej 
kohorty 267 pacjentów, którzy przeszli zabieg wymiany wyłącznie jednej zastawki 
(AVR) (model 2700) z czterech ośrodków z oryginalnego badania klinicznego nad 
osierdziową bioprotezą Carpentier‑Edwards PERIMOUNT.  Ta grupa składa się ze 
171 (64%) mężczyzn i 96 (36%) kobiet.  Średni wiek tych pacjentów w chwili 
implantacji (± odchylenie standardowe) wynosił 64,9 ± 11,8 roku przy zakresie 
wieku od 21 do 86 lat.  Łączna liczba danych w ilości 2407 pacjentolat była 
dostępna do analizy (2386 późnych pacjentolat).  Średni czas obserwacji 
kontrolnej wynosił 9,0 ± 5,5 lat, a maksymalnie 20,3 lat.  W okresie od 1981 r.  do 
1994 r.  doszło łącznie do 189 zgonów.  Czterdzieści osiem (25,3%) z tych 
189 zgonów zostało uznane za powiązane z zastawkami.  Metody obserwacji 
wykorzystywane w każdej klinice obejmowały wizyty w szpitalu, wizyty w 
gabinetach oraz kontakt telefoniczny lub listowny z pacjentem, jego rodziną lub 
miejscowym lekarzem.  
Tabela 5 podsumowuje współczynniki wolności od powikłań po 20 latach.  Stan 
pacjentów na ostatni okres obserwacji to 189 osób zmarłych (70,8%), 10 osób 
żyjących (3,8%), 46 osób poddanych zabiegowi usunięcia zastawki (17,2%) i 
22 osoby, z którymi utracono kontakt podczas okresu obserwacji (8,2%).  
W tej grupie pacjentów odnotowano 48 zgonów powiązanych z zastawką; do 
1 zgonu powiązanego z zastawką doszło w okresie operacyjnym i wynikał on z 
krwawienia.  Do dwudziestu ośmiu zgonów związanych z zastawką w okresie 
pooperacyjnym zaliczono 5 spowodowanych zaburzeniami 
zakrzepowo‑zatorowymi, 4 spowodowane zapaleniem wsierdzia/posocznicą, 
3 spowodowane strukturalnym uszkodzeniem protezy i 1 spowodowany 
krwawieniem.  Wystąpiło 15 innych zgonów, które rozpatrywano jako związane 
z zastawką ze względu na brak danych lub w związku z tym, że zgon został 
zaklasyfikowany jako powiązany z zastawką przez badacza.  Wolność aktuarialna 
od zgonu powiązanego z zastawką wynosiła 67,9 ± 6,6% po 20 latach.  
Dziewiętnaście dodatkowych zgonów były spowodowanych nieznanymi 
przyczynami lub nagłą śmiercią i mogło mieć związek z zastawką.  Te zgony 
zaklasyfikowano w sposób zachowawczy jako powiązane z zastawką; 
odpowiednio, wynikająca aktuarialna wolność od zgonu powiązanego z 
zastawką wynosiła 55,4 ± 6,4% po 20 latach.  

29
Wykazano także poprawę klasy czynnościowej NYHA w okresie pooperacyjnym.  
Zgodnie z ostatnimi wynikami obserwacji 108 pacjentów (44,8%) znajdowało 
się w I klasie czynnościowej NYHA.  
Niniejsze dane zostały skompilowane na podstawie wieloośrodkowego badania 
klinicznego prowadzonego przez firmę Edwards Lifesciences.  W celu uzyskania 
dodatkowych informacji na temat tego badania należy skontaktować się z 
Edwards Lifesciences LLC, Heart Valve Therapy Marketing Department, One 
Edwards Way, Irvine, CA 92614-5686.
Badanie potwierdzające
W okresie od sierpnia 2003 r.  do stycznia 2004 r.  60 pacjentom z pięciu 
ośrodków (dwóch europejskich i trzech kanadyjskich), wymagającym wymiany 
zastawki aortalnej (AVR) wszczepiono bioprotezę aortalną Carpentier-Edwards 
PERIMOUNT Magna, model 3000.  Wkrótce potem wprowadzono do protokołu 
klinicznego poprawki pozwalające na implantację bioprotezy aortalnej 
Carpentier-Edwards PERIMOUNT Magna, model 3000TFX, oraz dodanie trzech 
ośrodków amerykańskich.  Następnie, w okresie od grudnia 2004 r.  do grudnia 
2006 r. , 193 dodatkowym pacjentom wszczepiono model 3000TFX.  Model 
3000TFX różni się od modelu 3000 tym, że model 3000TFX jest poddawany 
procesowi ThermaFix.
W grupie modelu 3000TFX znajdowało się łącznie 116 mężczyzn (60,1%) i 
77 kobiet (39,9%) o średniej wieku w momencie wszczepienia rzędu 72,0 
(± 8,59 SD) lat i zakresie wieku od 26 do 89 lat.  Głównym wskazaniem do 
wymiany zastawki było zwężenie (78,2%), a w dalszej kolejności wada 
mieszana (14,5%) oraz niedomykalność (7,3%).
W połączonej grupie modeli 3000 i 3000TFX znajdowało się łącznie 
150 mężczyzn (59,3%) i 103 kobiety (40,7%) o średniej wieku w momencie 
wszczepienia rzędu 72,2 (± 8,31 SD) lata i zakresie wieku od 26 do 89 lat.  
Ponownie głównym wskazaniem do wymiany zastawki było zwężenie (77,5%), 
wada mieszana (15,4%) oraz niedomykalność (7,1%).
Stan pacjentów oceniano przedoperacyjnie, śródoperacyjnie, przy wypisywaniu 
ze szpitala, po 3 do 6 miesiącach, po 1 roku i następnie corocznie.  Skumulowana 
obserwacja dla modelu 3000TFX wynosiła 167 pacjentolat, ze średnim okresem 
obserwacji wynoszącym 0,9 roku (SD = 0,42, zakres = 0,0 do 2,1 roku); a 
skumulowana obserwacja dla obu modeli 3000 i 3000TFX łącznie wynosiła 
232 pacjentolat ze średnim okresem obserwacji wynoszącym 0,9 roku 
(SD = 0,42, zakres = 0,0 do 2,1 roku).  
Tabela 6 podsumowuje wczesne (≤ 30 dni) oraz późne pooperacyjne (> 30 dni) 
współczynniki zdarzeń niepożądanych związanych z zastawką dla, odpowiednio, 
grup modelu 3000TFX i połączonych modeli 3000/3000TFX.
Ta bela 7 ilustruje, według modelu zastawki, zmienne hemodynamiczne 
odnotowywane w elektrokardiogramach po jednym roku, wykonywanych na 
pacjentach w badaniach modelu 3000TFX i połączonych modeli 3000/3000TFX.
Tabela 8 prezentuję zmianę w klasie czynnościowej NYHA od oceny dokonywanej 
w momencie wyjściowym do wizyty po 1 roku.  Należy zwrócić uwagę na fakt, że 
w przypadku modelu 3000TFX odnotowano poprawę klasy czynnościowej na 
poziomie 56,5% dla wizyty po 1 roku.  Dla modelu grupy łączonej 3000/3000TFX 
odnotowano 60,9% poprawę klasy czynnościowej dla wizyty po 1 roku.
Kilka opublikowanych badań klinicznych demonstruje długoterminową trwałość 
osierdziowych bioprotez aortalnych Carpentier-Edwards PERIMOUNT, na 
podstawie których konstruowano osierdziowe bioprotezy aortalne 
Carpentier‑Edwards PERIMOUNT Magna oraz Magna Ease (poz.  14, 15, 16 & 17).  
Ponadto opublikowane dane pokazują, że bioproteza aortalna 
PERIMOUNT Magna wykazuje wyjątkowe parametry hemodynamiczne, z bardzo 
niskim ryzykiem niedopasowania pacjenta i protezy (poz.  18, 19, 20, 21, 22 & 23).
7.	 Indywidualizacja leczenia
We wszystkich przypadkach bez przeciwwskazań pacjenci z wszczepionymi 
bioprotezami zastawek serca powinni otrzymywać leczenie przeciwzakrzepowe 
podczas wstępnych etapów po implantacji indywidualnie, według zaleceń lekarza.  
Długoterminowe leczenie przeciwzakrzepowe i/lub przeciwpłytkowe należy 
rozważyć u pacjentów z czynnikami ryzyka zaburzeń zakrzepowo-zatorowych.  
Ostateczną decyzję w sprawie opieki nad konkretnym pacjentem powinien podjąć 
personel medyczny oraz pacjent, w świetle wszystkich okoliczności dotyczących 
tego pacjenta (poz.  12).  Bioproteza jest zalecana do AVR u pacjentów w każdym 
wieku, którzy nie będą przyjmować warfaryny lub mają poważne 
przeciwwskazania medyczne do leczenia warfaryną.  Preferencje pacjenta to 
racjonalne kryterium przy wyborze operacji wymiany zastawki aortalnej oraz 
wyborze protezy aortalnej.  Mechaniczna bioproteza jest rozsądnym wyborem do 
AVR u pacjentów poniżej 65 roku życia, którzy nie mają przeciwwskazania do 
leczenia przeciwzakrzepowego.  Bioproteza jest rozsądnym wyborem do AVR u 
pacjentów poniżej 65 roku życia, którzy wybrali wymianę zastawki ze względów 
związanych ze stylem życia po szczegółowych omówieniach ryzyka leczenia 
przeciwzakrzepowego względem prawdopodobieństwa konieczności 
przeprowadzenia kolejnego zabiegu AVR (poz.  12).
7.1	 Szczególne grupy pacjentów
Nie potwierdzono bezpieczeństwa ani skuteczności stosowania modelu 
bioprotez 11000A w następujących szczególnych populacjach, ponieważ nie 
przebadano ich w takich grupach:
 
• 
kobiety ciężarne;
 
• 
matki karmiące;
 
• 
pacjenci z nieprawidłowym metabolizmem wapnia (np. z przewlekłą 
niewydolnością nerek lub nadczynnością przytarczyc);
 
• 
pacjenci ze schorzeniami zwyrodnieniowymi aorty powodującymi 
powstawanie tętniaków (np.  martwica torbielowata błony środkowej, 
zespół Marfana);
 
• 
dzieci, młodzież lub młode osoby dorosłe.
Przestroga: Na podstawie doniesień w piśmiennictwie na temat zastawek 
tkankowych (poz.  6, 7, 8, 9 i 10) wydaje się występować zwiększony odsetek 
zwapnienia listków u pacjentów w wieku poniżej 20 lat.  W miarę możliwości 
należy unikać podawania w okresie pooperacyjnym wielokrotnych wstrzyknięć 
dożylnych zawierających wapń oraz unikać spożywania przez dzieci 
nadmiernych ilości mleka lub nabiału.  Wyniki badań prowadzonych na 
zwierzętach (poz.  11) wskazują, że wysoki poziom wapnia w organizmie może 
prowadzić do wczesnego powstawania zwapnień.
8.	 Informacja dla pacjenta
Po operacji zaleca się uważną i stałą obserwację lekarską (przynajmniej jedna 
wizyta rocznie), aby umożliwić rozpoznanie i właściwe leczenie powikłań 
związanych z bioprotezą, szczególnie wynikających z uszkodzenia materiału.  
Pacjentom z bioprotezą, którzy są w grupie podwyższonego ryzyka bakteriemii 
(np.  poddawanym zabiegom stomatologicznym), warto doradzić profilaktyczną 
terapię antybiotykową.  Pacjentom należy doradzać, aby zawsze nosili przy sobie 
Kartę danych wszczepu oraz informowali pracowników służby zdrowia o 
posiadanym implancie przy zasięganiu porady lekarskiej.
9.	 Sposób dostarczania
9.1 	 Opakowanie
Osierdziowa bioproteza aortalna Edwards model 11000A jest dostarczana w 
postaci jałowej i niepirogennej w opakowaniu tacowym z podwójną ochroną.  
Opakowanie tacowe z podwójną ochroną mieści się w torebce foliowej, która 
znajduje się w kartonie.

30
Każda bioproteza umieszczona jest w kartonie ze wskaźnikiem temperatury 
widocznym przez okienko na panelu bocznym.  Wskaźnik temperatury 
przeznaczony jest do identyfikacji produktów narażonych na przejściowe skrajne 
warunki temperaturowe.  W chwili otrzymania bioprotezy należy niezwłocznie 
sprawdzić wskaźnik i zapoznać się z etykietą kartonu, aby potwierdzić stan „Do 
wykorzystania”.  Jeśli stan „Do wykorzystania” nie jest oczywisty, nie należy 
używać bioprotezy i skontaktować się z lokalnym dostawcą lub 
przedstawicielem firmy Edwards Lifesciences w celu dokonania ustaleń 
dotyczących potwierdzenia zwrotu i wymiany.  
Ostrzeżenie: Dokładnie sprawdzić bioprotezę przed implantacją pod 
kątem dowodów ekspozycji na skrajne temperatury lub innych 
uszkodzeń.
9.2	 Przechowywanie
Osierdziową bioprotezę aortalną Edwards model 11000A należy przechowywać w 
temperaturze 10°C do 25°C (50-77°F), w torebce foliowej i na półce kartonowej.
10.	 Wskazówki dotyczące użycia
10.1	 Szkolenia lekarzy
Techniki implantacji niniejszej bioprotezy są podobne do stosowanych podczas 
wszczepiania ponad pierścieniem jakichkolwiek stentowych protez biologicznych 
zastawki aorty.  Przeszkolenie lekarzy nie jest konieczne do wykonywania 
implantacji osierdziowej bioprotezy aortalnej Edwards model 11000A.
10.2	 Kalibrowanie
Sprawdzić, czy akcesoria zostały wyjałowione zgodnie z zalecanymi instrukcjami 
dostarczonymi z akcesoriami wielorazowymi.
Kalibrowanie w implantacji nadpierścieniowej
W celu przeprowadzenia implantacji nadpierścieniowej pierścień do wszywania 
bioprotezy należy umieścić nad pierścieniem włóknistym, maksymalnie 
powiększając w ten sposób otwór zastawki.  Podczas dobierania rozmiaru do 
implantacji nadpierścieniowej kalibrator powinien być ułożony równolegle do 
płaszczyzny pierścienia; należy zastosować następującą technikę kalibracji:
Krok
Postępowanie
1
Używając kalibratora model 1133, wybrać cylindryczne 
zakończenie kalibratora o największej średnicy, które można 
bez trudu dopasować do pierścienia włóknistego pacjenta.
HVT21
Krok
Postępowanie
2
Po zweryfikowaniu odpowiedniego zakończenia cylindrycznego 
należy użyć zakończenia replikującego w tym samym rozmiarze, 
aby sprawdzić, czy pierścień do wszywania będzie dobrze 
dopasowany do górnej części pierścienia włóknistego.  Należy 
zwrócić szczególną uwagę na to, czy ujścia naczyń wieńcowych 
nie są zablokowane i czy wsporniki stentu zakończenia 
replikującego nie kolidują ze ścianą aorty przy połączeniu 
opuszkowo-komorowym.  Jeśli dopasowanie zakończenia 
replikującego jest satysfakcjonujące, do implantacji należy 
wybrać ten rozmiar bioprotezy.
HVT37
10.3	 Instrukcje dotyczące manipulacji i przygotowania
Zaleca się przeprowadzenie szkolenia w miejscu pracy przed rozpoczęciem 
manipulowania i przygotowania osierdziowej bioprotezy aortalnej Edwards, 
model 11000A.
Krok
Postępowanie
1
Przestroga: Nie otwierać opakowania osierdziowej 
bioprotezy aortalnej Edwards, model 11000A przed 
upewnieniem się, że dojdzie do implantacji.
Ostrzeżenie: Nie otwierać torebki foliowej w polu 
jałowym. Torebka foliowa stanowi jedynie osłonę 
zabezpieczającą. Jedynie najbardziej wewnętrzne 
opakowanie tacowe można wprowadzać do pola 
jałowego.
Po wyborze odpowiedniego rozmiaru bioprotezy należy, poza 
polem jałowym, wyjąć z kartonu torebkę foliową.  Przed 
otwarciem należy sprawdzić, czy opakowanie nie jest 
uszkodzone i czy nie brakuje pieczęci lub czy nie są one 
uszkodzone.
2
Należy przytrzymać podstawę tacy zewnętrznej w pobliżu pola 
jałowego i oderwać pokrywę tacy zewnętrznej.

35
23.	 Wagner, I. M. , et al.  Influence of Completely Supra-annular Placement of 
Bioprostheses on Exercise Hemodynamics in Patients With a Small Aortic 
Annulus.  J Thorac Cardiovascular Surg 2007; 133:1234-1241.
Niniejszy produkt jest wytwarzany i sprzedawany zgodnie z co najmniej jednym 
spośród następujących patentów amerykańskich: patenty amerykańskie nr: 
5,928,281; 5,931,969; 5,961,549; 6,102,944; 6,245,105; 6,413,275; 6,561,970; 
6,585,766; 6,837,902; 6,945,997; 7,214,344; 7,972,376; 8,007,992; 8,357,387; 
8,366,769; 8,632,608; i RE 40570; oraz odpowiadające patenty zagraniczne.  
Ponadto trwa uzyskiwanie innych patentów.
Należy zapoznać się z objaśnieniami symboli, umieszczonymi na końcu 
niniejszego dokumentu.

36
Tabela 2. Zestawienie współczynników powikłań, model 2700
Powikłanie
Grupa po izolowanej AVR
Populacja DVR
pooperacyjny 
% pacjentów
Okres  
pooperacyjny 
% na  
pacjentorok
% wolności  
od zdarzeń po  
sześciu latach  
(błąd standardowy)
pooperacyjny 
% pacjentów
Okres  
pooperacyjny 
% na  
pacjentorok
% wolności  
od zdarzeń po  
sześciu latach  
(błąd standardowy)
Zgon
Eksplantacja
Powtórny zabieg operacyjny  
związany z zastawką
Wszystkie przypadki  
powtórnej operacji
Zaburzenia zakrzepowo-zatorowe  
związane z zastawką
Wszystkie zdarzenia  
zakrzepowo-zatorowe
Zapalenie wsierdzia
Dysfunkcja zastawki
Przeciek okołoza-stawkowy
Powikłania krwotoczne leczenia
Hemoliza
Zakrzepica zastawki
4,7
0
 
0,7
 
22,4
 
3,1
 
5,0
0,6
0,1
0,1
1,4
0
0
4,6
0,3
 
0,1
 
1,8
 
1,5
 
2,4
0,8
0,7
0,3
0,4
0,2
0
73,5 (2,0)
98,5 (1,0)
 
99,8 (0,4)
 
75,4 (1,8)
 
91,4 (1,1)
 
84,9 (1,6)
95,8 (0,9)
96,0 (1,1)
98,8 (0,5)
96,4 (1,1)
99,1 (0,4)
100,0 (0)
12,9
0
 
0
 
34,3
 
1,4
 
5,7
1,4
0
0
4,3
0
0
4,2
0,8
 
0
 
2,3
 
5,1
 
6,6
1,5
0,4
1,2
2,3
0,4
0,4
67,2 (6,5)
N/D *
 
N/D *
 
N/D *
 
N/D *
 
N/D *
N/D *
N/D *
N/D *
N/D *
N/D *
N/D *
* N/D = Nie dotyczy
Tabela 3. Wyniki echokardiografii w okresie pooperacyjnym, model 2700
Rozmiar zastawki
19 mm
21 mm
23 mm
25 mm
27 mm
29 mm
Całkowita
Ogółem N
Śr.  liczba miesięcy po operacji
Prędkość przepływu (m/sek.)
	 średnia ± S. D.
	 n =
	 zakres 
Chwilowa wartość szczytowa 
gradientu (mmHg)
	 średnia ± S. D.
	 n =
	 zakres
12
28,6 ± 7,2
2,80 ± 0,49
12
1,90 - 3,60
 
32,22 ± 11,08
12
14,40 - 51,80
22
34,9 ± 8,6
2,56 ± 0,46
21
1,90 - 3,90
 
27,04 ± 10,49
21
14,40 - 60,80
15
36,9 ± 9,2
2,36 ± 0,42
15
1,39 - 2,86
 
23,00 ± 7,30
15
7,70 - 32,70
8
39,9 ± 7,6
2,15 ± 0,56
7
1,00 - 2,60
 
19,50 ± 8,16
7
4,00 - 27,00
3
31,4 ± 15,9
2,09 ± 0,27
3
1,90 - 2,40
 
17,60 ± 4,70
3
14,40 - 23,00
3
15,3 ± 12,2
2,08 ± 0,1
3
2,05 - 2,10
 
14,4 ± 0,58
3
13,95 - 15,06
63
34,6 ± 9,2
2,46 ± 0,50
61
1,00 - 3,90
 
25,67 ± 10,14
61
4,00 - 60,80

37
Tabela 4. Wyniki skuteczności, klasa czynnościowa NYHA, model 2700
Okres przedoperacyjny Klasa 
czynnościowa NYHA
Okres pooperacyjny  
Klasa czynnościowa NYHA
I
II
III
IV
Zgon
Brak dostępnych 
danych
I
II
III
IV
Niedostępne
18
140
181
43
5
19
37
48
16
1
4
2
1
9
35
72
53
2
15
24
2
2
Tabela 5. Współczynniki wolności od powikłań po 20 latach (n = 267), model 2700
Wolność od powikłań po 20 latach
Faktyczna
Aktuarialna
Liniowa (%/pacjentorok)
Zgony związane z zastawką
Zaburzenia zakrzepowo-zatorowe/zakrzepica
Krwawienie
Zapalenie wsierdzia/posocznica
Eksplantacja spowodowana SVD
≥ 60
≥ 65
> 70
85,8 ± 2,5%
82,4 ± 2,6%
94,0 ± 1,5%
91,7 ± 1,7%
92,6 ± 2,0%
96,3 ± 1,6%
96,0 ± 2,3%
67,9 ± 6,6%
68,2 ± 6,8%
91,7 ± 2,2%
89,3 ± 2,4%
77,1 ± 7,2%
81,5 ± 9,6%
69,9 ± 20,5%
1,2
1,7
0,4
0,8
b/z*
* Bez znaczenia. SVD nie występuje jako stała funkcja ryzyka; w rezultacie liniowe współczynniki nie są istotne.
Tabela 6. Podsumowanie zdarzeń niepożądanych związanych z zastawką, modele 3000 oraz 3000TFX
Zdarzenia niepożądane
≤ 30 dni po operacji
> 30 dni po operacji
3000TFX  
(N = 193) 
liczba zdarzeń 
(% pacjentów)
3000/3000TFX  
(N = 253) 
liczba zdarzeń 
(% pacjentów)
3000TFX  
(N = 193) 
liczba zdarzeń 
(% pacjentów)
3000/3000TFX  
(N = 253) 
liczba zdarzeń 
(% pacjentów)
Zaburzenia zakrzepowo-zatorowe związane z zastawką
Niestrukturalna dysfunkcja zastawki (PVL)
Eksplantacja (NSVD)
Zgon (zatrzymanie akcji serca, zdarzenie typu 
krwawienie, CVA)
Powtórny zabieg operacyjny
Hemoliza
Krwawienie związane z AC
Zapalenie wsierdzia
Strukturalne pogorszenie stanu zastawki
Zakrzepica zastawki
Inne (rozdarcie aorty)
6 (3,1)
3 (1,5)
2 (1,0)
 
1 (0,5)
1 (0,5)
1 (0,5)
0 (0,0)
0 (0,0)
0 (0,0)
0 (0,0)
1 (0,5)
7 (2,8)
4 (1,6)
2 (0,8)
 
1 (0,4)
1 (0,4)
1 (0,4)
0 (0,0)
0 (0,0)
0 (0,0)
0 (0,0)
1 (0,4)
3 (2,0)
3 (2,0)
0 (0,0)
 
3 (2,0)
1 (0,7)
3 (2,0)
2 (1,4)
0 (0,0)
0 (0,0)
0 (0,0)
0 (0,0)
3 (1,4)
3 (1,4)
0 (0,0)
 
3 (1,4)
1 (0,5)
3 (1,4)
2 (1,0)
0 (0,0)
0 (0,0)
0 (0,0)
0 (0,0)

38
Tabela 7. Zmienne hemodynamiczne w elektrokardiogramach dla kontroli po 1 roku, modele 3000 i 3000TFX
Rodzaj  
zastawki
Parametr
19 mm 
Średnia ± SD  
(n)
21 mm 
Średnia ± SD  
(n)
23 mm 
Średnia ± SD  
(n)
25 mm 
Średnia ± SD  
(n)
27 mm 
Średnia ± SD  
(n)
29 mm 
Średnia ± SD  
(n)
3000TFX
Średni gradient ciśnienia  
skurczowego (mmHg)
16,7 ± 4,7  
(10)
15,8 ± 4,4  
(18)
11,3 ± 3,7  
(45)
11,1 ± 4,1  
(37)
9,4 ± 4,3  
(12)
9,0 ± 0,0  
(2)
Frakcja  
wyrzutowa (%)
65,8 ± 10,4  
(10)
62,7 ± 9,4  
(19)
60,6 ± 11,3  
(48)
61,4 ± 11,2  
(38)
59,5 ± 10,7  
(12)
55,0 ±14,1  
(2)
EOA aorty  
(cm2)
1,2 ± 0,4  
(10)
1,5 ± 0,4  
(18)
1,8 ± 0,6  
(44)
1,8 ± 0,5  
(36)
2,1 ± 0,6  
(12)
2,1 ± 0,1  
(2)
3000/ 
3000TFX
Średni gradient ciśnienia  
skurczowego (mmHg)
16,7 ± 4,2  
(16)
13,8 ± 4,8  
(34)
11,7 ± 4,7  
(56)
11,0 ± 3,8  
(47)
9,5 ± 4,1  
(14)
9,0 ± 0,0  
(2)
Frakcja  
wyrzutowa (%)
62,1 ± 15,1  
(16)
58,6 ± 11,6  
(34)
60,2 ± 11,2  
(59)
60,2 ± 11,5  
(47)
58,5 ± 10,5  
(14)
55,0 ± 14,1  
(2)
EOA aorty  
(cm2)
1,3 ± 0,5  
(16)
1,5 ± 0,4  
(32)
1,8 ± 0,6  
(55)
1,8 ± 0,6  
(46)
2,1 ± 0,6  
(14)
2,1 ± 0,1  
(2)
Tabela 8. Klasa czynnościowa NYHA: Zmiana względem wartości wyjściowych dla wizyty kontrolnej po 1 roku, modele 3000 i 3000TFX
-----Wartości wyjściowe-----
Rodzaj zastawki
Klasa NYHA w  
okresie obserwacji
Klasa I
Klasa II
Klasa III
Klasa IV
Nie dotyczy
3000TFX
N = 193
Klasa I
10
33
51
10
3
Klasa II
2
8
13
2
1
Klasa III
-
-
3
-
-
Klasa IV
-
-
-
1
-
Zgon
-
3
16
1
-
Eksplantacja
-
-
3
-
-
Nie dotyczy
2
6
21
4
-
3000/ 
3000TFX
N = 253
Klasa I
12
40
71
11
3
Klasa II
2
14
29
3
1
Klasa III
-
-
3
-
-
Klasa IV
-
-
1
1
-
Zgon
-
3
19
2
-
Eksplantacja
-
-
3
-
-
Nie dotyczy
2
7
22
4
-
Klasa czynnościowa NYHA: Zmiana względem wartości wyjściowych dla wizyty kontrolnej po 1 roku
Rodzaj zastawki
Poprawa 
N (%)
Bez zmian 
N (%)
Pogorszenie 
N (%)
Nie dotyczy 
N (%)
3000TFX (N = 193)
109 (56,5)
22 (11,4)
2 (1,0)
60 (31,1)
3000/3000TFX (N = 253)
154 (60,9)
30 (11,9)
3 (1,2)
66 (26,1)

2
external stent diameter at the base.  The lip of the replica sizer 1173R replicates 
the sewing ring of the bioprosthesis, with its scalloped anterior portion and 
black markings, to determine the outcomes of specific suture or subvalvular 
apparatus preservation techniques.
The sizers 1173B and 1173R are labeled with the bioprosthesis size.  The 
complete set of sizers is housed in a tray, model SET1173, which can be reused 
and resterilized.
Figure 1a –  
1173B Barrel Sizer
Figure 1b –  
1173R Replica Sizer
CP1089-16
CP1089-15
Lip
Barrel
Tricentrix Holder System and Handles
The holder/handle assembly consists of two components: the Tricentrix holder 
system (Figure 2) that is mounted to the 11000M bioprosthesis, and a handle 
(1111, 1117, 1173, or 1126) that is attached to the Tricentrix holder system at 
the time of surgery.
Figure 2 – Tricentrix Holder System
CP1089-28
HVT55
The following handles (Table 2) may be used with the 11000M Bioprosthesis:
Table 2. Accessory Handles
Model
Shaft Material
Overall Length
Reusable
inch
cm
1111
Stainless steel
7. 0
17. 8
Yes
1117
Nitinol
9. 1
23. 2
Yes
1126
Stainless steel
11. 5
29. 2
No
1173
Nitinol
11. 3
28. 6
Yes
Handles with a nitinol shaft are more flexible than stainless steel.  With each 
sterilization cycle, they return to their original straight shape for easier 
attachment to the holder.
2.	 Indications for Use
The Edwards Pericardial Mitral Bioprosthesis, Model 11000M is indicated for 
patients who require replacement of their native or prosthetic mitral valve.
3.	 Contraindications
Do not use if the surgeon believes such would be contrary to the best interests of 
the patient.  The actual decision for or against the use of this bioprosthesis must 
remain with the surgeon who can evaluate all the various risks involved, 
including the anatomy and pathology observed at the time of surgery.
4.	 Warnings
FOR SINGLE USE ONLY. This device is designed, intended, and 
distributed for single use only. Do not re-sterilize or reuse this device. 
There are no data to support the sterility, nonpyrogenicity, and 
functionality of the device after sterile reprocessing. Exposure of the 
bioprosthesis or package to irradiation, steam, ethylene oxide, or 
other chemical sterilants will render the bioprosthesis unfit for use.
DO NOT FREEZE OR EXPOSE THE BIOPROSTHESIS TO EXTREME HEAT. 
Exposure of the bioprosthesis to extreme temperatures will render the 
device unfit for use. 
DO NOT USE the bioprosthesis:
• 
If the foil pouch, sealed trays, or lids are opened, damaged, or 
stained
• 
If the expiration date has elapsed, or
• 
If it has been dropped, damaged, or mishandled in any way. Should 
a bioprosthesis be damaged during insertion, do not attempt repair.
DO NOT EXPOSE the bioprosthesis to any solutions, chemicals, 
antibiotics, etc., except for sterile physiological saline solution. 
Irreparable damage to the leaflet tissue, which may not be apparent 
under visual inspection, may result.
DO NOT GRASP the leaflet tissue of the bioprosthesis with instruments 
or cause any damage to the bioprosthesis. Even the most minor leaflet 
tissue perforation may enlarge in time to produce significant 
impairment of valve function.
DO NOT OVERSIZE. Oversizing may cause bioprosthesis damage or 
localized mechanical stresses, which may in turn injure the heart or 
result in leaflet tissue failure, stent distortion and valve regurgitation.

3
DO NOT PASS CATHETERS, transvenous pacing leads, or any surgical 
instrument across the bioprosthesis with the exception of a surgical 
mirror used to examine struts and suture placement. Other surgical 
devices may cause leaflet tissue damage.
As with any implanted medical device, there is a potential for patient 
immunological response. Some components of the model 11000M are 
a metal alloy that contains cobalt, chromium, nickel, molybdenum, 
manganese, carbon, beryllium and iron. Care should be exercised in 
patients with hypersensitivities to these materials. This device was 
manufactured without latex, but may have been produced in a 
latex‑containing environment.
5.	 Adverse Events
5.1	 Observed Adverse Events
As with all prosthetic heart valves, serious adverse events, sometimes leading to 
death, may be associated with the use of tissue valves.  In addition, adverse 
events due to individual patient reaction to an implanted device or to physical or 
chemical changes to the components, particularly those of biological origin, 
may occur at varying intervals (hours or days) necessitating reoperation and 
replacement of the prosthetic device.
The Edwards Pericardial Mitral Bioprosthesis Model 11000M is similar in design 
to the Carpentier-Edwards PERIMOUNT Magna Mitral Ease pericardial 
bioprostheses model 7300TFX.  
Three (3) multi-center, non-randomized, prospective non-US clinical studies were 
conducted with the mitral pericardial bioprosthesis model 6900.  Three hundred 
one (301) patients had isolated mitral valve replacement (MVR) and 62 patients 
had double valve replacement (DVR), where the aortic valve was replaced with a 
Carpentier-Edwards PERIMOUNT pericardial bioprosthesis aortic model.
In the first study, bioprostheses were implanted between 1984 and 1986; in the 
second study, bioprostheses were implanted between 1989 and 1994; and in 
the third study, bioprostheses were implanted between 1996 and 1997.  
Patients were evaluated preoperatively, intraoperatively, at discharge, at 1 year, 
and annually thereafter.  Adverse events were captured throughout the 
postoperative period.  
Table 3 presents the observed rates for early events (≤ 30 days for valve-related 
adverse events), the linearized rates for late events (> 30 days postoperatively), 
and the actuarial adverse event rates at 1, 5, and 8 years postoperatively for 
model 6900.  The adverse event rates were based on 363 patients at nine 
centers.  The cumulative follow-up was 1100 patient-years with a mean 
follow‑up of 3. 0 years (SD = 2. 4 years, range = 0 to 8. 2 years).  Preoperative and 
operative patient demographics are presented in Tables 5 and 7.  Effectiveness 
results are presented in Tables 9 and 11.
One (1) multi-center, non-randomized, prospective international clinical study 
was conducted with patients implanted with the Carpentier-Edwards 
PERIMOUNT Plus pericardial bioprosthesis model 6900P mitral.  One hundred 
seventy five (175) patients had isolated mitral replacement (MVR) and 34 patients 
had double valve replacement (DVR), where the aortic valve was replaced with a 
Carpentier-Edwards PERIMOUNT pericardial bioprosthesis aortic model.  In this 
study, patients were implanted between 1999 and 2007.  Patients were evaluated 
preoperatively, intraoperatively at discharge, at 1 year, and annually thereafter.  
Adverse events were captured throughout the postoperative period.  Table 4 
presents the observed rates for early events (≤ 30 days for valve related adverse 
events), the linearized rates for late events (> 30 days postoperatively), and the 
actuarial adverse event rates at 1- and 5-years postoperatively for model 6900P.  
The adverse event rates were based on two hundred nine (209) patients at seven 
centers.  The cumulative follow-up was 873. 18 patient-years with a mean 
follow‑up of 4. 2 years (SD = 2. 3 years, range = 0 to 8. 2 years).  Preoperative and 
operative patient demographics are presented in Tables 6 and 8.  Effectiveness 
results are presented in Tables 10 and 12.
5.2	 Potential Adverse Events
Adverse events potentially associated with the use of bioprosthetic heart valves 
include:
• 
Angina
• 
Bleeding diatheses (coagulopathy) related to anticoagulant therapy
• 
Cardiac arrhythmias
• 
Coronary ostial blockage
• 
Endocarditis
• 
Heart failure
• 
Hemolysis
• 
Hemolytic anemia
• 
Hemorrhage
• 
Local and/or systemic infection
• 
Myocardial infarction
• 
Patient prosthetic mismatch (PPM)
• 
Prosthesis leaflet entrapment (Impingement)
• 
Prosthesis nonstructural dysfunction
• 
Prosthesis pannus
• 
Prosthesis perivalvular leak
• 
Prosthesis regurgitation
• 
Prosthesis structural deterioration
• 
Prosthesis thrombosis
• 
Stroke
• 
Thromboembolism
• 
Transient ischemic attack (TIA)
It is possible that these complications could lead to:
• 
Reoperation
• 
Explantation
• 
Permanent disability
• 
Death
Other adverse events associated with the use of Carpentier-Edwards PERIMOUNT 
mitral pericardial bioprostheses model 6900 compiled from the literature and 
from reports received through the Edwards Lifesciences complaint handling 
system include: stenosis, regurgitation through an incompetent valve, 
ventricular perforation by stent posts, malfunctions of the valve due to 
distortion at implant, and fracture of the wireform frame.
6.	 Clinical Studies
The safety endpoints captured in the prospective studies were adverse events; 
blood analyses were used to confirm the absence or presence of certain adverse 
events.  The safety results for model 6900 are provided in Table 3 and for model 
6900P in Table 4.  Preoperative patient demographics for model 6900 are 
provided in Table 5 and for model 6900P in Table 6.  Operative patient 
demographics for model 6900 are provided in Table 7 and for model 6900P in 
Table 8.  Effectiveness endpoints were New York Heart Association (NYHA) 
functional classification summarized in Table 9 for model 6900 and Table 10 for 

4
model 6900P and echocardiographic assessments summarized in Table 11 for 
model 6900 and Table 12 for model 6900P.
There are no clinical data presently available demonstrating increased resistance 
of the Edwards Pericardial Mitral Bioprosthesis Model 11000M to calcification as 
compared to other commercially available bioprostheses.
7.	 Individualization of Treatment
Bioprosthetic heart valve recipients should be maintained on anticoagulant 
therapy, except where contraindicated, during the initial stages after 
implantation, as determined by the physician on an individual basis.  Long-term 
anticoagulant and/or antiplatelet therapy should be considered for patients 
with risk factors for thromboembolism.
The ultimate judgment regarding care of a particular patient must be made by 
the healthcare provider and patient in light of all the circumstances presented 
by that patient (Ref.  7).  A bioprosthesis is recommended for MVR in patients of 
any age who will not take warfarin or who have major medical contraindications 
to warfarin therapy.  Patient preference is a reasonable consideration in the 
selection of mitral valve operation and valve prosthesis.  A mechanical prosthesis 
is reasonable for MVR in patients under 65 years of age who do not have a 
contraindication to anticoagulation.  A bioprosthesis is reasonable for MVR in 
patients under 65 years of age who elect to receive this valve for lifestyle 
considerations after detailed discussions of the risks of anticoagulation versus 
the likelihood that a second MVR may be necessary (Ref.  7).
7.1	 Specific Patient Populations
The safety and effectiveness of the Model 11000M bioprosthesis has not been 
established for the following specific populations because it has not been 
studied in these populations:
• 
patients who are pregnant;
• 
nursing mothers;
• 
patients with abnormal calcium metabolism (e.g., chronic renal failure, 
hyperparathyroidism);
• 
patients with aneurysmal aortic degenerative conditions (e.g., cystic medial 
necrosis, Marfan’s syndrome);
• 
children, adolescents, and young adults
Caution: Based on reports in the literature on tissue valves (Refs.  9, 10, 11, 12 & 13), 
there appears to be an increased incidence of leaflet calcification in patients under 
the age of 20.  When feasible, repeated intravenous injections containing calcium 
should be avoided during the postoperative period, and excessive milk or dairy 
product consumption should be avoided in children.  Animal research studies 
(Ref.  14) show that a high systemic calcium level can lead to early calcification.
8.	 Patient Counseling Information
Careful and continued medical follow-up (at least by an annual visit to the 
physician) is advised so that bioprosthesis-related complications, particularly 
those related to material failure, can be diagnosed and properly managed.  
Patients with bioprostheses are at risk from bacteremia (e. g. , undergoing dental 
procedures) and should be advised about prophylactic antibiotic therapy.  Patients 
should be encouraged to carry their Patient Identification Card at all times and to 
inform their healthcare providers that they have an implant when seeking care.
9.	 How Supplied
9.1	 Packaging
The Edwards Pericardial Mitral Bioprosthesis, Model 11000M, is provided sterile 
and non-pyrogenic, in a double barrier tray package.  The double tray package is 
in a foil pouch, which is in a carton.
Each bioprosthesis is contained in a carton with a temperature indicator 
displayed through a window on the side panel.  The temperature indicator is 
intended to identify products which have been exposed to transient 
temperature extremes.  Upon receipt of the bioprosthesis, immediately inspect 
the indicator and refer to the carton label to confirm a “Use” condition.  If the 
“Use” condition is not apparent, do not use the bioprosthesis and contact the 
local supplier or Edwards Lifesciences representative to make arrangements for 
return authorization and replacement.
Warning: Carefully inspect the bioprosthesis before implantation for 
evidence of extreme temperature exposure or other damage.
9.2	 Storage
The Edwards Pericardial Mitral Bioprosthesis, Model 11000M, should be stored 
at 10 °C to 25 °C (50-77 °F), in the foil pouch and shelf carton.
10.	 Directions for Use
10.1	 Physician Training
The techniques for implanting this bioprosthesis are similar to those for 
implanting any stented mitral bioprosthesis.  No special training is required to 
implant the Edwards Pericardial Mitral Bioprosthesis, Model 11000M.
10.2	 Sizing
Caution: Do not use other manufacturer’s valve sizers, or sizers for 
other Edwards Lifesciences valve prostheses to size the 11000M 
bioprosthesis.
Caution: Examine sizers and handles for signs of wear, such as dullness, 
cracking or crazing. Replace sizer or handle if any deterioration is 
observed.
Warning: Fragments of handles and sizers are not radiopaque and 
cannot be located by means of an external imaging device.
Verify that the accessories have been sterilized according to the recommended 
instructions provided with the reusable accessories.
The black marks on the lip replicate the black suture markers on the sewing ring.  
They delimit the anterior portion of the bioprosthesis sewing ring which should 
be positioned across the anterior intercommissural portion of the native 
annulus, in order to straddle the left ventricular outflow tract area.  The height 
and location of the stent posts are marked on the replica sizer 1173R to aid in 
assessing optimal alignment and seating.
The sizers include pre-attached handles with increased handle length for 
improved access in the case of a difficult exposure, a deep thoracic cage or 
minimally invasive access.  The posterior handle attachment to the sizer allows 
an unobstructed view through the barrel into the ventricle for assessment of 
subvalvular structures.  The sizers 1173B and 1173R are labeled with the 
bioprosthesis size.

8
10.4	 Device Implantation
Step
Procedure
1
The surgeon should be familiar with the recommendations for 
proper sizing and placement in the supra-annular position 
(See 10. 2 Sizing).
Because of the complexity and variation of cardiac valve 
replacement surgery, the choice of surgical technique, 
appropriately modified in accordance with the previously 
described Warnings, is left to the discretion of the individual 
surgeon.  In general, the following steps should be employed:
1.	 Surgically remove the diseased or damaged valve leaflets 
and all associated structures deemed necessary.
2.	 Surgically remove any calcium from the annulus to ensure 
proper seating of the sewing ring of the bioprosthesis to 
avoid damage to the delicate leaflet tissue.
3.	 Proper sizing.  Measure the annulus using only the mitral 
sizer models 1173B and 1173R (Figures 1a-1b).
4.	 Proper seating of the prosthesis; 
5.  	 Tying sutures with the holder in place to minimize the 
potential for suture looping or chordal entrapment; 
6.	 Examination of the bioprosthetic leaflets for distortion or 
leak during tying.
Caution: When choosing a bioprosthesis for a given 
patient, the size, age, and physical condition of the 
patient in relation to the size of the bioprosthesis must 
be taken into consideration to minimize the possibility 
of obtaining a suboptimal hemodynamic result. The 
selection of a bioprosthesis, however, must ultimately 
be made by the physician on an individual basis after 
carefully weighing all of the risks and benefits to the 
patient.
Caution: Adequate removal of calcium deposits from 
the patient’s annulus must be performed before 
implantation to avoid damage to the delicate 
bioprosthesis leaflet tissue as a result of contact with 
calcium deposits. Insert the sizer into the mitral 
annulus. The barrel of the sizer should always fit 
comfortably in the annulus. 
Caution: Use only sizers 1173B or 1173R during the 
selection of the bioprosthesis size; other sizers may 
result in improper valve selection (see 1.2 Accessory 
Description). Like other mitral bioprostheses, the 
Edwards Pericardial Mitral Bioprosthesis, Model 11000M 
is usually implanted using pledgeted mattress sutures. 
It is recommended to size the annulus after the sutures 
have been placed, as sutures may decrease the size of 
the bioprosthesis that can be implanted.
Step
Procedure
2
Proper orientation of the bioprosthesis:
Caution: The wireform frame of the Model 11000M 
bioprosthesis is symmetrical, and the three commissure 
supports (struts) are equally spaced. However, the 
sewing ring is designed for a specific orientation of the 
bioprosthesis. The scalloped part of the sewing ring, 
between the two silicone protrusions, should be placed 
across the intercommissural anterior portion of the 
annulus and straddle the left ventricular outflow tract.
The contrasting suture markers in the sewing ring are intended 
to aid in proper orientation and denote a typical 
intercommissural distance.  However, this distance may vary for 
each individual patient.  On the left side, two close black sutures 
indicate where the first stitch should be placed and correspond 
to the anterior commissure.  On the right side, only one black 
suture indicates the approximate location of the posterior 
commissure.  Using these orientation aids, the third post should 
naturally fall in place in or around the middle of the posterior 
leaflet location.
Caution: Special care must be exercised to avoid placing 
a strut in front of the left ventricular outflow tract, as it 
may impair the long-term hemodynamic performance.
3
Suture Placement:
A black suture guide line circles the sewing ring.  When placing 
sutures through the sewing ring, sliding drag forces are 
reduced when sutures are placed straight through the sewing 
ring and in the region from the suture guide line to the outer 
portion of the sewing ring.  
Firm tension must be maintained on the sutures as the 
bioprosthesis is lowered into the annulus; this minimizes the 
potential for formation of suture loops that might entrap a 
leaflet.  This, when combined with the fully retracted stent 
posts when the Tricentrix holder system is in place, helps guide 
the sutures into their correct position behind the struts and 
onto the sewing ring.  
Remove the handle prior to tying the sutures.  The handle and 
blue adapter must be removed as an assembly.  Maintain the 
bioprosthesis placement in the annulus by gently placing 
forceps or gloved hands onto the holder and cutting the green 
thread on the blue adapter.  Remove the blue adapter and 
handle assembly as one unit.
CP1089-27
Adapter

10
13.	 References
1.	 Marchand MA. , et al.  Fifteen-year Experience with the Mitral 
Carpentier‑Edwards PERIMOUNT Pericardial Bioprosthesis.  Ann Thorac Surg. 
2001; 71:S236-9.
2.	 Liao K. , et al.  Bovine Pericardium versus Porcine Aortic Valve: Comparison of 
Tissue Biological Properties As Prosthetic Valves; Artificial Organs.  
1992;16(4):361-5.
3.	 Vesely I. , et al.  Comparison of the Compressive Buckling of Porcine Aortic 
Valve Cusps and Bovine Pericardium.  J. Heart Valve Dis. January 1998; 
7(1):34-9.
4.	 Carpentier A.  From Valvular Xenograft to Valvular Bioprosthesis 
(1965‑1977).  Med. Instrum.  1977; 11(2):98-101.
5.	 Carpentier A. , et al.  Continuing Improvements in Valvular Bioprostheses.  
J. Thorac. Cardiovasc. Surg.  1982; 83(1):27-42.
6.	 Arounlangsy P. , et al.  Histopathogenesis of early stage mitral annular 
calcification.  J. Med Dent Sci.  2004; 51(1):35-44.
7.	 Bonow RO. , et al.  ACC/AHA Guidelines for the Management of Patients With 
Valvular Heart Disease: A Report of the American College of Cardiology/
American Heart Association Task Force on Practice Guidelines (Committee 
on Management of Patients with Valvular Heart Disease).  J. Am Coll Cardiol.  
2006; 48:e1-148.
8.	 Aagaard J. , et al.  Mitral valve replacement with total preservation of native 
valves and subvalvular apparatus.  J. Heart Valve Dis.  May 1997; 6(3):274-8; 
discussion 279-80.
9.	 Jamieson,W. R. E. , et al.  Carpentier‐Edwards Standard Porcine Bioprosthesis: 
Primary Tissue Failure (Structural Valve Deterioration) by Age Groups.  Ann 
Thorac Surg 1988, 46:155‐162.
10.	 Odell, J. A.  Calcification of Porcine Bioprostheses in Children.  In Cohn, L.  and 
V.  Gallucci (eds): Cardiac Bioprostheses.  Yorke Medical Books.  New York, 
1982, pp 231‐237.
11.	 Reul, G. J. , et al.  Valve Failure with the lonescu‐Shiley Bovine Pericardial 
Bioprosthesis: Analysis of 2680 Patients.  J. Vasc Surg 1985, 2(1):192‐204.
12.	 Sanders, S. P. , et al.  Use of Hancock Porcine Xenografts in Children and 
Adolescents.  Am J. Cardiol 1980, 46(3):429‐438.
13.	 Silver, M. M. , et al.  Calcification in Porcine Xenograft Valves in Children.  
Am J. Cardiol 1980, 45:685‐689.
14.	 Carpentier, A. , et al.  Continuing Improvements in Valvular Bioprostheses.  
J. Thorac Cardiovasc Surg 1982, 83(1):27‐42.
Prices subject to change without notice.  This product is manufactured and 
distributed under at least one or more of the following U. S.  Patents: US-Patent 
Nos.  5,928,281; 5,931,969; 5,961,549; 6,102,944; 6,245,105; 6,413,275; 
6,416,547; 6,561,970; 6,585,766; 6,837,902; 6,945,997; 6,966,925; RE 40570; 
7,214,344; 7,658,763; 7,682,391; 7,972,376; 8,007,992; 8,357,387; and 
8,632,608; and corresponding foreign patents.  Likewise, additional patents 
pending.
Refer to the symbol legend at the end of this document.

12
Table 5: Preoperative Patient Demographics (Model 6900)
Variable
Category
Study Characteristics (N = 363; 1100 total pt-yrs. )
n
% (n/N)1
Age at implant (N = 363)
Mean ± SD
66. 1 ± 10. 7
Gender
Female/Male
212/151
58. 4%/41. 6%
Diagnosis/Etiology
None
30
8. 3%
Stenosis
91
25. 1%
Regurgitation
184
50. 7%
Mixed Disease
58
16. 0%
Note:
1.	 n = number of patients in each category; N = total number of study patients.
Table 6: Preoperative Patient Demographics (Model 6900P)
Variable
Category
Study Characteristics (N = 209; 873. 18 total pt-yrs. )
n
% (n/N)1
Age at implant (N = 209)
Mean ± SD
71. 4 ± 9. 4
Gender
Female/Male
138/71
66. 0%/34. 0%
Diagnosis/Etiology
Mixed Disease
48
23. 0%
Regurgitation
121
57. 9%
Stenosis
32
15. 3%
Valve Dysfunction
8
3. 8%
Note:
1.	 n = number of patients in each category; N = total number of study patients.

13
Table 7: Operative Patient Demographics (Model 6900)
Study Characteristics 
(N = 363; 1100 total pt-yrs. )
Variable
Category
n
% (n/N)1
Etiology2
Rheumatic heart disease
135
37. 2%
Calcification
82
22. 6%
Degeneration
50
13. 8%
Endocarditis
39
10. 7%
Failed Bioprosthesis
15
4. 1%
Ischemic Heart Disease
14
3. 9%
Congenital Abnormalities
8
2. 2%
Other
44
12. 1%
Concomitant Procedures2
None
200
55. 1%
CABG3
78
21. 5%
Tricuspid Repair
61
16. 8%
Intra-aortic balloon pump
17
4. 7%
Pacemaker4
6
1. 7%
Aortic repair/replacement
5
1. 4%
Aneurysm Repair
4
1. 1%
Other
31
8. 5%
Pre-existing Conditions2
None
122
33. 6%
CAD5/CABG
72
19. 8%
Hypertension
61
16. 8%
Atrial Fibrillation
53
14. 6%
Previous MI6
45
12. 4%
Cerebrovascular Disease 
36
9. 9%
Other
234
64. 5%
Valve Size (mm)
25
22
6. 1%
27
110
30. 3%
29
137
37. 7%
31
81
22. 3%
33
13
3. 6%
Notes:
1.  	 n = number of patients in each category; N = total number of study patients
2.  	 May be more than one per patient
3.  	 CABG = Coronary Artery Bypass Graft
4.  	 Permanent or temporary
5.  	 CAD = Coronary Artery Disease
6.  	 MI = Myocardial Infarction

14
Table 8: Operative Patient Demographics (Model 6900P)
Study Characteristics 
(N = 209; 873. 18 total pt-yrs. )
Variable
Category
n
% (n/N)1
Etiology2
Calcified
38
18. 2%
Congenital
1
0. 5%
Degenerative
105
50. 2%
Endocarditis Remote
10
4. 8%
Ischemic
12
5. 7%
Rheumatic
64
30. 6%
Other
36
17. 2%
Concomitant Procedures2
None
91
43. 5%
Aortic Valve/Annulus Repair
3
1. 4%
CABG3
58
27. 8%
Permanent Pacemaker
1
0. 5%
Tricuspid Valve/Annulus Repair
21
10. 0%
Other
78
37. 3%
Pre-existing Conditions2
None
17
8. 1%
Arrhythmias
95
45. 5%
CAD4
85
40. 7%
Cardiomyopathy
13
6. 2%
Congestive Heart Failure
66
31. 6%
Endocarditis
14
6. 7%
Myocardial Infarction
21
10. 0%
Peripheral Vascular Disease
9
4. 3%
Pulmonary Hypertension
66
31. 6%
Rheumatic Fever
16
7. 7%
Systemic Hypertension
49
23. 4%
TIA5/CVA6
24
11. 5%
Other
35
16. 7%
Valve Size (mm)
25
28
13. 4%
27
37
17. 7%
29
84
40. 2%
31
43
20. 6%
33
17
8. 1%
Notes:
1.  	 n = number of patients in each category; N = total number of study patients
2.  	 May be more than one per patient
3.  	 CABG = Coronary Artery Bypass Graft
4.  	 CAD = Coronary Artery Disease
5.  	 TIA = Transient Ischemic Attack
6.	 CVA = Cerebral Vascular Accident

15
Table 9: Effectiveness Outcomes, Functional NYHA (Model 6900)
NYHA Functional Class
Preoperative 
Assessment
Postoperative Assessments
1 to 2 Year
5 Year
n/N1
%
n/N
%
n/N
%
I
11/363
3. 0
120/268
44. 8
40/129
31. 0
II
73/363
20. 1
90/268
33. 6
25/129
19. 4
III
192/363
52. 9
15/268
5. 6
1/129
0. 8
IV
84/363
23. 1
0/268
0. 0
0/129
0. 0
Not Available
3/363
0. 8
43/268
16. 0
63/129
48. 8
Note:
1.  	 n = number of patients in each category; N = total number of study patients.
Table 10: Effectiveness Outcomes, Functional NYHA (Model 6900P)
NYHA Functional Class
Preoperative  
Assessment
Postoperative Assessments
1 Year
5 Year
n/N1
%
n/N
%
n/N
%
I
6/209
2. 9
86/187
46. 0
30/96
31. 3
II
27/209
12. 9
68/187
36. 4
33/96
34. 4
III
121/209
57. 9
8/187
4. 3
6/96
6. 3
IV
55/209
26. 3
1/187
0. 5
0/96
0. 0
Not Available
0/209
0. 0
24/187
12. 8
27/96
28. 1
Note:
1.  	 n = number of patients in each category; N = total number of study patients.

20
Français
Bioprothèse mitrale péricardique 
d’Edwards, modèle 11000M
Mode d’emploi
ATTENTION : dispositif expérimental. Limité à une utilisation 
expérimentale en vertu des lois fédérales (États-Unis).
AVERTISSEMENT : dispositif expérimental. Exclusivement à des fins de 
recherche clinique.
Avertissement : dispositif expérimental. Utilisation limitée à la 
recherche. Pour une utilisation par des (médecins) chercheurs qualifiés 
uniquement.
1.	 Description du dispositif et des accessoires
1.1	 Description du dispositif
La bioprothèse mitrale péricardique d’Edwards, modèle 11000M, est une 
bioprothèse trivalve composée d’un péricarde bovin traité installé sur une 
structure flexible.  Elle est disponible dans les tailles suivantes : 25, 27, 29, 31 et 
33 mm (tableau 1).  Elle est conservée dans un emballage non aqueux et ne 
nécessite pas de rinçage avant l’implantation.
Le fil métallique est fait d’un alliage de chrome-cobalt recouvert d’un matériau 
tissé en polyester.  Une bande laminée en alliage de chrome-cobalt et film en 
polyester entoure la base de la structure en fil métallique.
Un anneau de suture gaufré en silicone, qui est couvert d’un tissu poreux en 
polytétrafluoroéthylène (PTFE), est attaché à la structure en fil métallique.  
L’anneau de suture est crénelé sur sa partie antérieure.  Les marqueurs de suture en 
soie noire de la partie antérieure contribuent à orienter la bioprothèse et à éviter 
que la voie d’évacuation du ventricule droite ne soit obstruée par un montant.
L’anneau de suture est encerclé par une ligne de guidage de suture en soie 
noire.  L’utilisation de cette ligne pour positionner les sutures à travers l’anneau 
de suture et dans la région sur la partie externe de l’anneau de suture facilite la 
pénétration de l’aiguille et donne une compliance variable.  Les cellules du 
gaufrage sont plus larges dans la partie postérieure, là où les calcifications et les 
irrégularités de l’anneau mitral d’origine sont plus fréquentes (réf.  6).  
Tableau 1. Dimensions nominales
HVT63
Taille
25  
mm
27  
mm
29  
mm
31  
mm
33  
mm
A.  Diamètre de l’endoprothèse 
(fil métallique, mm)
25
27
29
31
31
B.  Diamètre de l’anneau tissulaire 
(mm)
28
29,5
31,5
33,5
33,5
C.  Diamètre du montant de 
l’endoprothèse externe 
(embout, mm)
29
31
34
35
35
D.  Diamètre de l’anneau de suture 
externe (en mm)
36
38
40
42
44
E.  Profil effectif antérieur (mm)
7
7,5
8
8,5
8,5
F.  Profil effectifpostérieur (mm)
10
10,5
11
11,5
11,5
G.  Hauteur profil total (mm)
15
16
17
18
18
Surface de l’orifice (en mm2)
424
499
580
653
653
1.2	 Description des accessoires
Les accessoires pouvant être utilisés avec la bioprothèse 11000M sont les suivants :
• 
Système de support Tricentrix
• 
Calibreur pour réplique 1173R
• 
Calibreur pour porteuse 1173B
• 
Plateau de stérilisation fourni avec le modèle SET1173
• 
Modèles de poignée 1111, 1117, 1173 et 1126 (pour utilisation unique)
Tous les accessoires sont vendus non stériles, sauf le système de support 
Tricentrix qui est fixé à la bioprothèse stérile et la poignée 1126 qui est réservée 
à une utilisation unique.
Calibreurs et plateau
Seuls les calibreurs 1173B (figure 1a) et 1173R (figure 1b) peuvent être 
employés avec la bioprothèse 11000M.
Attention : pour calibrer la bioprothèse 11000M, ne pas utiliser de 
calibreurs de valves d’autres fabricants ou d’autres prothèses de valves 
d’Edwards Lifesciences.
N’utiliser que les calibreurs 1173B ou 1173R pour définir la taille à employer pour 
la bioprothèse 11000M.  Les calibreurs 1173B et 1173R permettent de constater 
immédiatement si la prothèse s’adapte à l’anneau et sont proposés pour chaque 
taille de bioprothèse 11000M.  Le corps des calibreurs 1173B et 1173R indique le 
diamètre de l’endoprothèse à la base.  Grâce à sa partie antérieure crénelée et à 
ses marqueurs noirs, la lèvre du calibreur 1173R reproduit l’anneau de suture de 
Edwards Lifesciences, le logo E stylisé, Edwards, Carpentier-Edwards, Tricentrix, 
PERIMOUNT, PERIMOUNT Magna, PERIMOUNT Plus, TFX et Magna Mitral Ease 
sont des marques de commerce d’Edwards Lifesciences Corporation.

21
la bioprothèse et permet de déterminer les résultats de la suture ou des 
techniques de préservation de l’appareil sous-valvulaire.
Les calibreurs 1173B et 1173R portent une étiquette indiquant la taille de la 
bioprothèse.  La trousse complète de calibreurs se trouve dans un plateau, 
modèle SET1173, qui peut être réutilisé et restérilisé.
Figure 1a – Calibreur  
pour porteuse 1173B
Figure 1b – Calibreur  
pour réplique 1173R
CP1089-16
CP1089-15
Lèvre
Corps
Système de support Tricentrix et poignées
L’ensemble de poignée et support est constitué de deux composants : le 
système de support Tricentrix (figure 2) monté sur la bioprothèse 11000M, et 
une poignée (1111, 1117, 1173 ou 1126) fixée au système de support Tricentrix 
lors de l’opération chirurgicale.
Figure 2 – Système de support Tricentrix
CP1089-28
• Support
• Adaptateur
• Montant
• Clip
• Manchon
Manchon
Valve
Support
Adaptateur
Poignée
Clip
Système de support Tricentrix
Montant
HVT55
Les poignées suivantes (tableau 2) peuvent être utilisées avec la bioprothèse 
11000M.
Tableau 2. Poignées accessoires
Modèle
Matériau de l’axe
Longueur totale
Réutilisable
pouces
cm
1111
Acier inoxydable
7,0
17,8
Oui
1117
Nitinol
9,1
23,2
Oui
1126
Acier inoxydable
11,5
29,2
Non
1173
Nitinol
11,3
28,6
Oui
Les poignées équipées d’un axe en nitinol sont plus souples que celles en acier 
inoxydable.  Lors de chaque cycle de stérilisation, elles redeviennent droites, ce 
qui facilite leur fixation au support.
2.	 Mode d’emploi
La bioprothèse mitrale péricardique d’Edwards, modèle 11000M, est destinée 
aux patients dont il faut remplacer la valve mitrale d’origine ou prothétique.
3.	 Contre-indications
Ne pas utiliser la bioprothèse si le chirurgien estime que son utilisation est 
contraire à l’intérêt du patient.  La décision finale à ce propos relève du 
chirurgien qui doit évaluer tous les risques impliqués, y compris l’anatomie et la 
pathologie observées au moment de l’opération chirurgicale.
4.	 Mises en garde
POUR UTILISATION UNIQUE SEULEMENT. Ce dispositif est conçu, destiné 
et distribué pour une utilisation unique seulement. Ne pas restériliser 
ou réutiliser ce dispositif. Aucune donnée n’existe pour corroborer le 
caractère stérile, la non-pyrogénicité et la fonctionnalité du dispositif 
après le processus de restérilisation. La bioprothèse et l’emballage 
deviendront inutilisables en cas d’exposition à des radiations, à la 
vapeur, à l’oxyde d’éthylène ou à d’autres agents chimiques de 
stérilisation.
NE PAS CONGELER NI EXPOSER LA BIOPROTHÈSE À UNE CHALEUR 
EXTRÊME. L’exposition de la bioprothèse à des températures extrêmes 
rendra le dispositif inutilisable.
NE PAS UTILISER la bioprothèse :
• 
si le sachet métallisé, les plateaux scellés ou les lèvres sont ouverts, 
endommagés ou tachés ;
• 
si la date d’expiration est passée ;
• 
si elle est tombée, endommagée ou mal manipulée de quelle que 
façon que ce soit. Si une bioprothèse est endommagée lors de 
l’insertion, ne pas tenter de la réparer.
NE PAS EXPOSER la bioprothèse à des solutions, des produits chimiques, 
des antibiotiques, etc., à l’exception de solutions salines 
physiologiques. Le tissu de la valve peut comporter des dommages 
irréparables non apparents lors d’une inspection visuelle.
NE PAS SAISIR le tissu de la valve de la bioprothèse avec des 
instruments ni endommager la bioprothèse. Même la plus petite 
perforation du tissu de la valve peut s’agrandir à terme et 
compromettre gravement son fonctionnement.

22
NE PAS CHOISIR UNE TAILLE SUPÉRIEURE. Le choix d’une taille 
supérieure peut entraîner des dommages à la bioprothèse ou un stress 
mécanique localisé, susceptible de blesser le cœur ou de causer une 
panne du tissu de la valve, une distorsion de l’endoprothèse ou une 
régurgitation du tissu de la valve.
NE PAS PASSER, à travers la bioprothèse, des cathéters, des sondes 
électrodes transveineuses ou d’autres instruments chirurgicaux autres 
qu’un miroir servant à vérifier le positionnement des montants et des 
sutures. Les autres dispositifs risquent d’endommager le tissu de la valve.
Comme pour tout dispositif médical implanté, il existe un risque de 
réponse d’immunisation de la part du patient. Certains composants du 
modèle 11000M sont en alliage contenant du cobalt, du chrome, du 
nickel, du molybdène, du manganèse, du carbone, du béryllium et du 
fer. Il faut prendre des précautions avec les patients souffrant 
d’hypersensibilité à ces matières. Ce dispositif ne contient pas de latex 
mais peut avoir été fabriqué dans un environnement qui en contient.
5.	 Évènements indésirables
5.1	 Évènements indésirables observés
Comme pour toutes les valves cardiaques prothétiques, des évènements 
indésirables graves pouvant parfois aller jusqu’au décès peuvent survenir.  En 
outre, des évènements indésirables découlant de la réaction du patient au 
dispositif implanté ou encore d’une modification physique ou chimique de ses 
composants, plus particulièrement de ceux dont l’origine est biologique, peuvent 
survenir à des intervalles variables (allant de plusieurs heures à plusieurs jours) et 
nécessitent une nouvelle opération pour remplacer la prothèse.
La conception de la bioprothèse mitrale péricardique d’Edwards, modèle 
11000M, est similaire à celle des bioprothèses péricardiques PERIMOUNT 
Magna Mitral Ease du modèle 7300TFX de Carpentier-Edwards.
Trois (3) essais cliniques multicentre prospectifs non randomisés ont été 
effectués hors des États-Unis avec la bioprothèse mitrale péricardique 6900.  Sur 
l’ensemble des patients, trois cent un (301) ont subi un remplacement isolé de 
la valve mitrale (RVM) tandis que 62 subissaient un double remplacement 
valvulaire (DRV), la valve aortique étant remplacée par une bioprothèse aortique 
péricardique PERIMOUNT de Carpentier-Edwards.
Les bioprothèses ont été implantées de 1984 à 1986 dans la première étude, de 
1989 à 1994 dans la deuxième et de 1996 à 1997 dans la troisième.  Les patients 
ont été évalués avant l’opération, pendant l’opération, à la sortie, après 1 an et 
tous les ans par la suite.
Le tableau 3 présente les taux observés d’évènements précoces (≤ 30 jours pour 
les évènements indésirables en lien avec la valve), le taux linéarisé pour les 
évènements tardifs (> 30 jours postopératoires) et les taux actuariels 
d’évènements indésirables 1, 5 et 8 ans après l’opération pour le modèle 6900.  
Les taux d’évènements indésirables concernaient 363 patients de neuf centres.  
Le suivi cumulatif était de 1 100 patient-années, avec une moyenne de suivi de 
3 années (écart-type = 2,4 années, intervalle = 0 à 8,2 ans).  Les données 
démographiques des patients en période préopératoire et opératoire sont 
présentées dans les tableaux 5 et 7.  Les résultats en matière d’efficacité sont 
présentés dans les tableaux 9 et 11.
Un (1) essai clinique multicentre prospectif non randomisé a été effectué à 
l’échelon international auprès de patients ayant reçu la bioprothèse mitrale 
péricardique PERIMOUNT 6900P de Carpentier-Edwards.  Sur l’ensemble des 
patients, cent soixante-quinze (175) ont subi un remplacement isolé de la valve 
mitrale (RVM) tandis que trente-quatre (34) subissaient un double 
remplacement (DRV), la valve aortique étant remplacée par une bioprothèse 
aortique péricardique PERIMOUNT de Carpentier-Edwards.  Dans cette étude, les 
bioprothèses ont été implantées de 1999 à 2007.  Les patients étaient évalués 
pendant la période préopératoire, pendant la période péropératoire et à la 
sortie, après 1 an et chaque année par la suite.  Les évènements indésirables ont 
été consignés tout au long de la période postopératoire.  Le tableau 4 présente 
les taux observés d’évènements précoces (≤ 30 jours pour les évènements 
indésirables en lien avec la valve), le taux linéarisé pour les évènements tardifs 
(> 30 jours postopératoires) et les taux actuariels d’évènements indésirables 
1 et 5 ans après l’opération pour le modèle 6900P.  Les taux d’évènements 
indésirables concernaient deux cent neuf (209) patients de sept centres.  Le suivi 
cumulatif était de 873,18 patient-années, avec une moyenne de suivi de 
4,2 années (écart-type = 2,3 années, intervalle = 0 à 8,2 ans).  Les données 
démographiques des patients en période préopératoire et opératoire sont 
présentées dans les tableaux 6 et 8.  Les résultats en matière d’efficacité sont 
présentés dans les tableaux 10 et 12.
5.2	 Évènements indésirables potentiels
Les évènements indésirables potentiels associés à l’utilisation de biovalves 
cardiaques prothétiques sont les suivants :
• 
Angine de poitrine
• 
Diathèse hémorragique (coagulopathie) 
en lien avec l’anticoagulothérapie
• 
Arythmie cardiaque
• 
Blocage de la valve ostiale coronaire
• 
Endocardite
• 
Insuffisance cardiaque
• 
Hémolyse
• 
Anémie hémolytique
• 
Hémorragie
• 
Infection locale et systémique
• 
Infarctus du myocarde
• 
Inadaptation de la prothèse au patient
• 
Enclavement de la valve prothétique (coincement)
• 
Dysfonction non structurelle de la prothèse
• 
Pannus de la prothèse
• 
Fuite périvalvulaire de la prothèse
• 
Régurgitation de la prothèse
• 
Détérioration de la structure de la prothèse
• 
Thrombose prothétique
• 
Accident vasculaire cérébral
• 
Thrombo-embolie
• 
Insuffisance cardiaque congestive
Ces complications peuvent avoir les conséquences suivantes :
• 
Nouvelle opération chirurgicale
• 
Explantation
• 
Handicap permanent
• 
Décès
Voici les autres évènements indésirables en lien avec l’utilisation des 
bioprothèses mitrales péricardiques PERIMOUNT 6900 de Carpentier-Edwards 
tirés de la documentation et des rapports issus du système de gestion des 

23
plaintes d’Edwards Lifesciences : sténose, régurgitation par une valve 
insuffisante, perforation du ventricule par les montants de l’endoprothèse, 
dysfonction de la valve découlant d’une déformation de l’implant et rupture de 
la structure métallique.
6.	 Études cliniques
Les indicateurs de sécurité mentionnés dans les études prospectives 
correspondent aux évènements indésirables.  Des analyses sanguines ont été 
utilisées pour confirmer l’absence ou la présence de certains évènements 
indésirables.  Les résultats concernant la sécurité sont détaillés dans le tableau 3 
pour le modèle 6900 et dans le tableau 4 pour le modèle 6900P.  Les données 
démographiques préopératoires sont détaillées dans le tableau 5 pour le modèle 
6900 et dans le tableau 6 pour le modèle 6900P.  Les données démographiques 
opératoires sont détaillées dans le tableau 7 pour le modèle 6900 et dans le 
tableau 8 pour le modèle 6900P.  Les indicateurs d’efficacité correspondent à la 
classification fonctionnelle de la New York Heart Association (NYHA), résumée 
dans le tableau 9 pour le modèle 6900 et dans le tableau 10 pour le modèle 
6900P, et aux évaluations échocardiographiques résumées dans le tableau 11 
pour le modèle 6900 et dans le tableau 12 pour le modèle 6900P.
Il n’existe aucune donnée clinique démontrant la résistance accrue à la 
calcification de la bioprothèse mitrale péricardique d’Edwards, modèle 11000M, 
par rapport aux autres bioprothèses du marché.
7.	 Individualisation du traitement
Sauf indication contraire, les destinataires de la valve bioprothétique doivent 
suivre une anticoagulothérapie pendant les premiers stades suivant 
l’implantation, selon les consignes données à chacun par le médecin.  Une 
anticoagulothérapie ou un traitement antiplaquettaire à long terme doit être 
envisagé pour les patients montrant des facteurs de risque de thrombo-embolie.
Le jugement final concernant les soins pour un patient donné doit être pris par 
le fournisseur de santé et le patient à la lumière de l’ensemble de la situation 
que présente ce dernier (réf.  7).  Il est recommandé de poser une bioprothèse en 
cas de RVA sur des patients de tous âges qui ne prennent pas de warfarine ou 
pour lesquels il existe une contre-indication importante à la thérapie à base de 
warfarine.  Les préférences du patient sont également à prendre en compte dans 
une mesure raisonnable lors du choix de l’opération de la valve mitrale et de la 
valve prothétique.  Il est raisonnable d’envisager l’implantation d’une prothèse 
mécanique pour un RVA de patients de moins de 65 ans pour lesquels 
l’anticoagulation n’est pas contre-indiquée.  Il est également raisonnable 
d’envisager l’implantation d’une bioprothèse pour un RVA de patients de moins 
de 65 ans qui ont fait ce choix pour des raisons de mode de vie après avoir été 
informés dans les détails des risques de l’anticoagulation par rapport à 
l’éventuelle nécessité d’un deuxième RVA (réf.  7).  
7.1	 Populations de patients spécifiques
L’innocuité et l’efficacité de la bioprothèse, modèle 11000M, n’ont pas été établies 
pour les populations suivantes, sur lesquelles elles n’ont pas été étudiées :
• 
patientes enceintes ;
• 
mères qui allaitent ;
• 
patients métabolisant le calcium de manière anormale (p. ex., insuffisance 
rénale, hyperparathyroïdisme) ;
• 
patients présentant une insuffisance dégénérative anévrismale de l’aorte 
(p.  ex. , nécrose médiale kystique, syndrome de Marfan) ;
• 
enfants, adolescents et jeunes adultes.
Attention : Selon des rapports issus de documentation sur des valves tissulaires 
(réf.  9, 10, 11, 12 et 13), la fréquence des calcifications de la valve serait 
supérieure chez les patients de moins de 20 ans.  Lorsque cela est possible, il faut 
éviter les injections intraveineuses répétées contenant du calcium pendant la 
période postopératoire.  Parallèlement, la consommation excessive de lait ou de 
produits laitiers doit être évitée chez l’enfant.  À cet égard, les recherches 
effectuées sur les animaux (réf.  14) démontrent qu’un niveau élevé de calcium 
dans le système peut entraîner une calcification précoce.  
8.	 Informations et conseils au patient
Il est conseillé de procéder à un suivi sérieux et continu (au moins par une visite 
annuelle chez le médecin) afin que les complications liées à la bioprothèse, et 
plus particulièrement aux problèmes de matériau, puissent faire l’objet d’un 
diagnostic et d’un traitement adaptés.  Les patients porteurs de bioprothèses 
sont vulnérables à la bactériémie (p.  ex. , lors de procédures dentaires) et doivent 
recevoir des conseils concernant l’antibioprophylaxie.  Enfin, il faut encourager 
les patients à porter en permanence leur carte d’identification et à informer les 
fournisseurs dont ils sollicitent des soins qu’ils possèdent un implant.
9.	 Présentation
9.1	 Conditionnement
La bioprothèse mitrale péricardique d’Edwards, modèle 11000M, est stérile et 
non pyrogène.  Elle est livrée dans un emballage de plateau à double barrière 
placé dans un sachet métallisé, se trouvant lui-même dans un carton.
Chaque bioprothèse se trouve dans un carton avec un indicateur de température 
visible à travers une fenêtre sur le panneau latéral.  Cet indicateur vise à repérer 
les produits exposés à des températures extrêmes transitoires.  À la réception de 
la bioprothèse, inspecter immédiatement l’indicateur et consulter l’étiquette du 
carton pour confirmer l’état « Utiliser ».  Si l’état « Utiliser » n’est pas apparent, 
ne pas se servir de la bioprothèse et contacter le fournisseur local ou le 
représentant d’Edwards Lifesciences pour organiser une autorisation de retour 
et un remplacement.
Mise en garde : inspecter soigneusement la bioprothèse avant 
l’implantation pour trouver des traces d’exposition à des températures 
extrêmes ou d’autres dégâts.
9.2	 Stockage
La bioprothèse mitrale péricardique d’Edwards, modèle 11000M, doit être 
entreposée à une température comprise entre 10 °C et 25 °C (50 °F et 77 °F), 
dans son sachet métallisé et son carton de rangement.
10.	 Directives d’utilisation
10.1	 Formation du médecin
Les techniques d’implantation de cette bioprothèse sont semblables à celles du 
placement d’une bioprothèse mitrale avec endoprothèse.  Aucune formation 
particulière n’est nécessaire pour implanter la bioprothèse mitrale péricardique 
d’Edwards, modèle 11000M.
10.2	 Choix de la taille
Attention : pour calibrer la bioprothèse 11000M, ne pas utiliser de 
calibreurs de valves d’autres fabricants ou d’autres prothèses de valves 
d’Edwards Lifesciences.
Attention : vérifier si les calibreurs et les poignées contiennent des traces 
d’usure comme des ternissures, des fissurations ou des craquelures. 
Remplacer le calibreur ou la poignée en cas de détériorations.
Mise en garde : les fragments des poignées et des calibreurs ne sont pas 
radio-opaques et ne peuvent pas être détectés par un imageur externe.
Vérifier que les accessoires ont été stérilisés conformément aux 
recommandations fournies avec les articles réutilisables.

27
10.4	 Implantation du dispositif
Étape
Procédure
1
Le chirurgien doit être familier avec les recommandations 
concernant la mesure et le positionnement supra-annulaire 
(voir la section 10. 2 Choix de la taille. )
À cause de la complexité et de la variété du remplacement 
chirurgical de la valve cardiaque, le choix de la technique 
chirurgicale, correctement modifiée selon les mises en garde 
décrites précédemment, est à la discrétion du chirurgien 
individuel.  En général, les étapes suivantes doivent être suivies :
1.	 Retirer par chirurgie les valves malades ou endommagées 
ainsi que toutes les structures associées au besoin.
2.	 Retirer par chirurgie le calcium de l’anneau afin d’assurer un 
bon positionnement de l’anneau de suture de la bioprothèse 
pour éviter d’endommager le tissu délicat de la valve.
3.	 Choisir la bonne taille.  Mesurer l’anneau exclusivement à 
l’aide du calibreur mitral 1173B ou 1173R (figures 1a et 1b).
4.	 Bien positionner la prothèse.
5.	 Nouer les sutures une fois le support en place pour éviter 
qu’elles ne forment une boucle ou que la membrane ne se 
coince.
6.	 Examiner les valves de la bioprothèse pour repérer les 
déformations ou les fuites pouvant être survenues lors de 
l’étape précédente.
Attention : lors d’un choix d’une bioprothèse, il faut 
prendre en compte la taille, l’âge et l’état physique par 
rapport à la taille de la bioprothèse, afin de minimiser 
le risque d’hémodynamique sous-optimale. Toutefois, 
le choix final revient au médecin après l’évaluation des 
risques et des avantages pour le patient.
Attention : il faut éliminer adéquatement les 
calcifications de l’anneau du patient avant 
l’implantation pour éviter que le tissu délicat de la valve 
bioprothétique ne s’endommage à leur contact. Insérer 
le calibreur dans l’anneau mitral. Le corps devrait 
toujours s’y adapter dans peine.
Attention : n’utiliser que des calibreurs 1173B ou 1173R 
pour choisir la taille de la bioprothèse. L’emploi d’autres 
calibreurs peut conduire à un choix non adapté (voir 
1.2 Description des accessoires). Comme pour les autres 
bioprothèses mitrales, l’implantation de la bioprothèse 
mitrale péricardique d’Edwards, modèle 11000M, 
s’effectue généralement par la technique de suture 
discontinue matelassée. Cette technique est 
recommandée pour choisir la taille de l’anneau après le 
placement des sutures, ces dernières pouvant réduire 
la taille de la bioprothèse pouvant être implantée.
Étape
Procédure
2
Orientation adéquate de la bioprothèse :
Attention : le fil métallique de la bioprothèse, modèle 
11000M, est symétrique, et les trois supports des 
commissures (montants) sont équidistants. L’anneau de 
suture est cependant conçu en fonction d’une orientation 
donnée de la bioprothèse. La partie crénelée de l’anneau 
de suture, entre les deux protubérances en silicone, doit 
être placée face à la partie intercommissurale antérieure 
de l’anneau et enjamber la région de la voie d’évacuation 
du ventricule gauche.
Les marqueurs de suture en contraste de l’anneau de suture 
indiquent la bonne orientation et la distance type entre les 
commissures.  Cette distance peut cependant varier d’un patient 
à l’autre.  Sur le côté gauche, deux sutures noires rapprochées 
indiquent où placer le premier point et correspondent à la 
commissure antérieure.  
Le côté droit comporte une seule suture noire qui indique 
l’emplacement approximatif de la commissure postérieure.  
Lorsque ces guides d’orientation sont utilisés, le troisième 
montant se positionne naturellement vers le milieu de 
l’emplacement de la valve postérieure.
Attention : il convient de bien faire attention à ne pas 
placer un montant en face de la voie d’évacuation du 
ventricule gauche, car il pourrait compromettre le 
rendement hémodynamique sur le long terme.
3
Positionnement de la suture :
L’anneau de suture est encerclé par une ligne de guidage de 
suture en soie noire.  Lors du positionnement des sutures à 
travers l’anneau de suture, la force de glissement est réduite 
lorsque les sutures sont placées directement à travers l’anneau 
de suture et dans la région, de la ligne de guidage à la partie 
externe de l’anneau de suture.
Il faut maintenir une tension sur les sutures pendant que la 
bioprothèse est enfoncée dans l’anneau, afin de réduire les 
risques de formation de boucles susceptibles de coincer une 
valve.  Une fois les montants d’endoprothèse complètement 
rétractés après la mise en place du système de support 
Tricentrix, il sera plus facile de guider les sutures vers la position 
adaptée derrière les montants et sur l’anneau de suture.

28
Étape
Procédure
Retirer la poignée avant de nouer les sutures.  La poignée et 
l’adaptateur bleu doivent être retirés en même temps.  
Maintenir la position de la bioprothèse dans l’anneau en plaçant 
délicatement le forceps ou les mains recouvertes de gants sur le 
support et en coupant le fil vert de l’adaptateur bleu.  Retirer 
l’adaptateur bleu et la poignée en une seule opération.
CP1089-27
Adaptateur
4
Attention : éviter d’enrouler ou de coincer une suture 
autour des cages ouvertes, des montants libres ou des 
supports de commissures de la bioprothèse, sous peine 
de compromettre le bon fonctionnement de la valve. 
Pour réduire les risques d’enroulement des sutures, il 
est essentiel de laisser le support déployé en place 
jusqu’à ce que tous les nœuds soient faits.
Cependant, si le support gêne la vision du chirurgien, il faut 
nouer toutes les sutures proches des trois montants du cadre 
avant de couper les trois fils de fixation du support vert pour 
enlever le support.
Attention : si les fils de fixation du support déployé 
sont coupés avant que les sutures adjacentes ne soient 
nouées, le support n’empêchera plus l’enroulement 
des sutures autour des montants de la structure.
Il faut bien prendre soin d’éviter de nouer les sutures en haut 
des coins des tiges grises du support.  Avant de nouer chaque 
suture, examiner les valves tout en tenant les deux brins sous 
tension.  La déformation ou le déplacement des valves pendant 
cette étape indique que la suture est enroulée autour d’un 
montant.  Il ne faut pas relâcher la tension sur les sutures avant 
ou après le retrait du support, sous peine de favoriser la 
formation de boucles et de coincer les sutures.  Il est conseiller 
de passer un miroir chirurgical à travers les valves après le 
retrait du support afin d’examiner chaque montant ainsi que 
le positionnement des sutures.
Attention : lors de sutures séparées, il est important de 
les couper près des nœuds et de veiller à ce que le bout 
exposé n’entre pas en contact avec le tissu de la valve 
(réf. 8). 
Étape
Procédure
Voici comment retirer le système de support Tricentrix en une 
seule opération à la fin des sutures :
CP1089-14
1.	 À l’aide d’un scalpel ou de ciseaux placés uniquement dans 
le canal de coupe, couper chacune des trois (3) sutures 
vertes exposées.  Ne jamais tenter de couper une suture sous 
un support partiellement détaché, car un fragment pourrait 
tomber dans le ventricule.  Éviter de couper ou 
d’endommager l’endoprothèse ou le tissu de la valve en 
même temps que les sutures.
2.	 Après avoir coupé les trois (3) sutures du support, retirer le 
système de support Tricentrix de la bioprothèse en une seule 
opération, en même temps que vous nouez les sutures, en 
utilisant des gants ou des forceps protégés.
3.	 Après l’implantation, retirer et jeter la baguette.
10.5	 Nettoyage et stérilisation des accessoires
Les accessoires de la bioprothèse mitrale péricardique d’Edwards, modèle 
11000M, sont emballés à part.  La poignée du modèle 1126 est stérile et est 
destinée à un usage unique.  Les poignées des modèles 1111, 1117 et 1173 et les 
calibreurs 1173B et 1173R ne sont pas stériles et doivent être nettoyés et 
stérilisés avant l’utilisation.  Les poignées, les calibreurs, la base et le couvercle 
du plateau doivent être nettoyés et stérilisés à nouveau avant chaque 
utilisation.  Consulter le mode d’emploi fourni avec les accessoires réutilisables 
pour connaitre les consignes de nettoyage et de stérilisation.
10.6	 Retour de la bioprothèse
Edwards Lifesciences souhaite obtenir des échantillons cliniques recouverts de la 
bioprothèse mitrale péricardique d’Edwards, modèle 11000M, à des fins d’analyse.  
Pour retourner des bioprothèses recouvertes, contacter votre représentant.
• 
Emballage non ouvert avec la barrière stérile intacte : si le sachet métallisé 
ou les plateaux n’ont pas été ouverts, retourner la bioprothèse dans son 
emballage d’origine.
• 
Emballage ouvert, mais avec la bioprothèse non implantée : si le plateau est 
ouvert, la bioprothèse n’est plus stérile.  Si la bioprothèse n’est pas 
implantée, elle doit être placée dans un fixateur histologique adapté 
comme du méthanediol à 10 % ou du glutaraldéhyde à 2 %, puis retournée 
à l’entreprise.  La réfrigération n’est pas nécessaire dans ces circonstances.
• 
Bioprothèse explantée : la bioprothèse explantée doit être placée dans un 
fixateur histologique adapté comme du méthanediol à 10 % ou du 
glutaraldéhyde à 2 %, puis retournée à l’entreprise.  La réfrigération n’est 
pas nécessaire dans ces circonstances.

31
Tableau 5 : Données démographiques préopératoires (modèle 6900)
Variable
Catégorie
Caractéristiques de l’étude (N = 363; 1 100 total pt-an)
n
% (n/N)1
Âge lors de l’implantation (N = 363)
Moyenne ± écart-type
66,1 ± 10,7
Sexe
Fém. /masc.
212/151
58,4%/41,6%
Diagnostique/étiologie
Aucune
30
8,3%
Sténose
91
25,1%
Régurgitation
184
50,7%
Maladies mixtes
58
16,0%
Remarque :
1.	 n = nombre de patients pour chaque catégorie; N = total de patients de l’étude.
Tableau 6 : Données démographiques préopératoires (modèle 6900P)
Variable
Catégorie
Caractéristiques de l’étude (N = 209; 873,18 total pt-an)
n
% (n/N)1
Âge lors de l’implantation (N = 209)
Moyenne ± écart-type
71,4 ± 9,4
Sexe
Fém. /masc.
138/71
66,0%/34,0%
Diagnostique/étiologie
Maladies mixtes
48
23,0%
Régurgitation
121
57,9%
Sténose
32
15,3%
Dysfonction de la valve
8
3,8%
Remarque :
1.	 n = nombre de patients pour chaque catégorie; N = total de patients de l’étude.

32
Tableau 7 : Données démographiques des patients en période opératoire (modèle 6900)
Caractéristiques de l’étude 
(N = 363; 1 100 total pt-an)
Variable
Catégorie
n
% (n/N)1
Étiologie2
Rhumatisme cardiaque
135
37,2%
Calcification
82
22,6%
Dégénération
50
13,8%
Endocardite
39
10,7%
Bioprothèse défectueuse
15
4,1%
Cardiopathie ischémique
14
3,9%
Anomalies congénitales
8
2,2%
Autre
44
12,1%
Procédures concomitantes2
Aucune
200
55,1%
PA3
78
21,5%
Réparation tricuspidienne
61
16,8%
Pompe à ballonnet intra aortique
17
4,7%
Stimulateur cardiaque4
6
1,7%
Réparation/remplacement aortique
5
1,4%
Réparation d’un anévrisme
4
1,1%
Autre
31
8,5%
Affections préexistantes2
Aucune
122
33,6%
C5 / PA
72
19,8%
Hypertension
61
16,8%
Fibrillation auriculaire
53
14,6%
IM antérieur6
45
12,4%
Maladie cérébrovasculaire
36
9,9%
Autre
234
64,5%
Taille de la valve (mm)
25
22
6,1%
27
110
30,3%
29
137
37,7%
31
81
22,3%
33
13
3,6%
Remarques :
1.  	 n = nombre de patients pour chaque catégorie; N = total des patients de l’étude
2.  	 Possibilité de plus d’un par patient
3.  	 PA = Pontage aortocoronarien
4.  	 Permanent ou temporaire
5.  	 C = Coronaropathie
6.  	 IM = Infarctus du myocarde

33
Tableau 8 : Données démographiques des patients en période opératoire (modèle 6900P)
Caractéristiques de l’étude 
(N = 209; 873,18 total pt-an)
Variable
Catégorie
n
% (n/N)1
Étiologie2
Calcification
38
18,2%
Congénital
1
0,5%
Dégénératif
105
50,2%
Endocardite récente
10
4,8%
Ischémique
12
5,7%
Rhumatismal
64
30,6%
Autre
36
17,2%
Procédures concomitantes2
Aucune
91
43,5%
Réparation valve/anneau aortique
3
1,4%
PA3
58
27,8%
Stimulateur cardiaque permanent
1
0,5%
Réparation de la valve/anneau tricuspide
21
10,0%
Autre
78
37,3%
Affections préexistantes2
Aucune
17
8,1%
Arythmie
95
45,5%
C6
85
40,7%
Myocardiopathie
13
6,2%
Insuffisance cardiaque congestive
66
31,6%
Endocardite
14
6,7%
Infarctus du myocarde
21
10,0%
Maladie vasculaire périphérique
9
4,3%
Hypertension artérielle pulmonaire
66
31,6%
Fièvre rhumatismale
16
7,7%
Hypertension généralisée
49
23,4%
AIT4/AVC5
24
11,5%
Autre
35
16,7%
Taille de la valve (mm)
25
28
13,4%
27
37
17,7%
29
84
40,2%
31
43
20,6%
33
17
8,1%
Remarques :
1.  	 n = nombre de patients pour chaque catégorie; N = total des patients de l’étude
2.  	 Possibilité de plus d’un par patient
3.  	 PA = Pontage aortocoronarien
4.  	 AIT = accident ischémique transitoire
5 .	 AVC = accident vasculaire cérébral
6.  	 C = Coronaropathie

34
Tableau 9 : Résultats en matière d’efficacité, classification fonctionnelle NYHA (modèle 6900)
Classification fonctionnelle 
de la NYHA
Évaluation  
préopératoire
Évaluations postopératoires
1 à 2 ans
5 ans
n/N1
%
n/N
%
n/N
%
I
11/363
3,0
120/268
44,8
40/129
31,0
II
73/363
20,1
90/268
33,6
25/129
19,4
III
192/363
52,9
15/268
5,6
1/129
0,8
IV
84/363
23,1
0/268
0,0
0/129
0,0
Non disponible
3/363
0,8
43/268
16,0
63/129
48,8
Remarque :
1.  	 n = nombre de patients pour chaque catégorie; N = total de patients de l’étude.
Tableau 10 : Résultats en matière d’efficacité, classification fonctionnelle NYHA (modèle 6900P)
Classification fonctionnelle 
de la NYHA
Évaluation  
préopératoire
Évaluations postopératoires
1 an
5 ans
n/N1
%
n/N
%
n/N
%
I
6/209
2,9
86/187
46,0
30/96
31,3
II
27/209
12,9
68/187
36,4
33/96
34,4
III
121/209
57,9
8/187
4,3
6/96
6,3
IV
55/209
26,3
1/187
0,5
0/96
0,0
Non disponible
0/209
0,0
24/187
12,8
27/96
28,1
Remarque :
1.  	 n = nombre de patients pour chaque catégorie; N = total de patients de l’étude.

39
Polski
Osierdziowa bioproteza mitralna 
Edwards model 11000M
Instrukcja użytkowania
PRZESTROGA: Urządzenie badawcze. Prawo federalne (Stanów 
Zjednoczonych Ameryki) ogranicza użytkowanie tego urządzenia do 
celów badawczych.
PRZESTROGA: Urządzenie badawcze. Wyłącznie do badań klinicznych.
Przestroga: Urządzenie badawcze. Przeznaczone wyłącznie do celów 
badawczych. Do stosowania wyłącznie przez wykwalifikowanych 
badaczy (lekarzy).
1.	
Opis urządzenia i akcesoriów
1.1	 Opis urządzenia
Osierdziowa bioproteza mitralna Edwards model 11000M jest trójpłatkową 
bioprotezą wykonaną z odpowiednio przygotowanego wołowego osierdzia, 
umocowaną na elastycznej ramie.  Jest dostępna w rozmiarach 25, 27, 29, 31 i 
33 mm (Tabela 1).  Bioproteza jest przechowywana w opakowaniu niewodnym i 
nie wymaga przemywania przed wszczepieniem.
Prowadnica druciana jest wykonana ze stopu kobaltowo-chromowego i jest 
pokryta tkaniną poliestrową.  Stop kobaltowo-chromowy/warstwa laminatu 
poliestrowego otacza podstawę ramy prowadnicy drucianej.
Silikonowy pierścień do wszywania o strukturze waflowej, pokryty porowatą 
tkaniną politetrafluoroetylenową (PTFE), jest przymocowany do ramy 
prowadnicy drucianej.  Pierścień do wszywania jest obrębiony wzdłuż przedniej 
części.  Szwy znacznikowe z czarnego jedwabiu na przedniej części ułatwiają 
ułożenie bioprotezy i pomagają zapobiec zablokowaniu drogi odpływu z lewej 
komory przez rozpórkę.
Linia prowadząca szew z czarnego jedwabiu otacza pierścień do wszywania.  
Umieszczanie szwów przechodzących przez pierścień do wszywania i w regionie 
od linii prowadzącej szew do zewnętrznej części pierścienia do wszywania 
ułatwia penetrację igły i zapewnia zmienną zgodność.  W strukturze waflowej 
komórki są szersze wzdłuż części tylnej, gdzie w naturalnym pierścieniu 
mitralnym częstsze są zwapnienia i nieregularności (poz.  6).  
Tabela 1: Wymiary nominalne
HVT63
Rozmiar
25  
mm
27  
mm
29  
mm
31  
mm
33  
mm
A.  Średnica stentu (prowadnica 
druciana, mm)
25
27
29
31
31
B.  Średnica pierścienia tkanki (mm)
28
29,5
31,5
33,5
33,5
C.  Zewnętrzna średnica wspornika 
stentu (końcówka, mm)
29
31
34
35
35
D.  Zewnętrzna średnica pierścienia 
do wszywania (mm)
36
38
40
42
44
E.  Efektywny profil – część 
przednia (mm)
7
7,5
8
8,5
8,5
E.  Efektywny profil – część tylna 
(mm)
10
10,5
11
11,5
11,5
G.  Całkowita wysokość profilu (mm)
15
16
17
18
18
Powierzchnia geometryczna 
otworu (mm2)
424
499
580
653
653
1.2	 Opis akcesoriów
Do bioprotezy 11000M dostępne są następujące akcesoria:
• 
system uchwytu Tricentrix
• 
kalibrator replikujący 1173R
• 
kalibrator cylindra 1173B
• 
taca do wyjaławiania dostarczana z modelem SET1173
• 
modele rękojeści 1111, 1117, 1173 i 1126 (do jednorazowego użytku)
Wszelkie akcesoria są dostarczane jako niejałowe, z wyjątkiem systemu uchwytu 
Tricentrix, dostarczanego w postaci jałowej i dołączonego do jałowej bioprotezy, 
oraz rękojeści 1126, dostarczanej w postaci jałowej i przeznaczonej do 
jednokrotnego użycia.
Kalibratory i taca
Z bioprotezą 11000M można stosować wyłącznie modele kalibratorów 1173B 
(Rysunek 1a) lub 1173R (Rysunek 1b).
Przestroga: Do określania rozmiaru bioprotezy 11000M nie należy 
używać kalibratorów zastawkowych innych producentów ani 
kalibratorów przeznaczonych do innych protez zastawkowych firmy 
Edwards Lifesciences.
Do ustalenia odpowiedniego rozmiaru bioprotezy 11000M należy używać 
wyłącznie kalibratorów model 1173B i 1173R.  Kalibratory 1173B i 1173R 
umożliwiają bezpośrednią obserwację dopasowania w pierścieniu włóknistym.  Są 
dostarczane dla każdego z dostępnych rozmiarów bioprotezy 11000M.  Cylindry 
kalibratorów model 1173B i 1173R wskazują zewnętrzną średnicę stentu przy 
Edwards Lifesciences, logo stylizowanej litery E, Edwards, Carpentier-Edwards, 
Tricentrix, PERIMOUNT, PERIMOUNT Magna, PERIMOUNT Plus, TFX i 
Magna Mitral Ease to znaki towarowe firmy Edwards Lifesciences Corporation.

40
podstawie.  Krawędź kalibratorów replikujących 1173R powiela kształt pierścienia 
do wszywania bioprotezy z jego przednią, obrębioną częścią oraz czarnymi 
znacznikami.  Ma to na celu lepsze ustalenie wyników stosowania specyficznych 
technik wszywania lub technik zabezpieczenia aparatu podzastawkowego.
Kalibratory 1173B i 1173R są oznaczone rozmiarem bioprotezy.  Kompletny 
zestaw kalibratorów jest umieszczony na tacy model SET1173, którą można 
ponownie wykorzystywać i sterylizować.
Rysunek 1a – 1173B 
kalibrator cylindra
Rysunek 1b – 1173R 
kalibrator replikujący
CP1089-16
CP1089-15
Krawędź
Cylinder
 
System uchwytu Tricentrix i rękojeści
Zespół uchwyt/rękojeść składa się z dwóch części: systemu uchwytu Tricentrix 
(Rysunek 2), który jest mocowany do bioprotezy 11000M, i rękojeści (1111, 
1117, 1173 lub 1126), która jest dołączana do systemu uchwytu Tricentrix 
podczas zabiegu.
Rysunek 2 – System uchwytu Tricentrix
CP1089-28
• Uchwyt
• Adapter
• Trzon
• Zacisk
• Tuleja
Tuleja
Zastawka
Uchwyt
Adapter
Rękojeść
Zacisk
System uchwytu Tricentrix
Trzon
HVT55
Poniższe rękojeści (Tabela 2) mogą być stosowane z bioprotezą 11000M:
Tabela 2. Rękojeści akcesoriów
Model
Materiał korpusu
Całkowita długość
Do  
wielokrotnego  
użytku
cale
cm
1111
Stal nierdzewna
7,0
17,8
Tak
1117
Nitinol
9,1
23,2
Tak
1126
Stal nierdzewna
11,5
29,2
Nie
1173
Nitinol
11,3
28,6
Tak
Rękojeści o trzonie nitinolowym są elastyczniejsze od uchwytów ze stali 
nierdzewnej.  Po każdym cyklu wyjaławiania powracają do oryginalnego, 
prostego kształtu, co pozwala na łatwiejsze przymocowanie uchwytu.
2.	 Wskazania do stosowania
Osierdziowa bioproteza mitralna Edwards model 11000M jest przeznaczona dla 
pacjentów wymagających wymiany naturalnej lub protetycznej zastawki mitralnej.
3.	 Przeciwwskazania
Nie należy stosować produktu, jeżeli chirurg sądzi, że jego użycie jest sprzeczne 
z dobrem pacjenta.  To on powinien podjąć decyzję dotyczącą zastosowania tej 
bioprotezy lub zrezygnowania z jej użycia, ponieważ może ocenić różne czynniki 
ryzyka związane z jej wszczepieniem, w tym również budowę anatomiczną 
pacjenta oraz zmiany patologiczne widoczne podczas operacji.
4.	 Ostrzeżenia
WYŁĄCZNIE DO JEDNORAZOWEGO UŻYTKU. Opisywane urządzenie jest 
zaprojektowane i rozprowadzane wyłącznie z zamiarem jednorazowego 
użytku i takie jest jego przeznaczenie. Urządzenia nie wolno sterylizować 
ani stosować ponownie. Nie istnieją żadne dane potwierdzające 
jałowość, niepirogenność i sprawność produktu po ponownej sterylizacji. 
Wystawienie bioprotezy lub pojemnika na działanie promieniowania, 
pary, tlenku etylenu lub innych chemicznych środków sterylizujących 
spowoduje, że bioproteza będzie niezdatna do użytku.
NIE WOLNO ZAMRAŻAĆ BIOPROTEZY ANI PODDAWAĆ DZIAŁANIU 
SKRAJNIE WYSOKIEJ TEMPERATURY. Narażenie bioprotezy na skrajne 
temperatury uczyni urządzenie niezdatnym do użycia.
Bioprotezy NIE NALEŻY UŻYWAĆ:
• 
jeśli torebka foliowa, zapieczętowane tace lub pokrywy są otwarte, 
uszkodzone lub zabrudzone
• 
jeśli minął termin ważności lub
• 
jeśli została upuszczona, zniszczona lub postępowano z nią w 
niewłaściwy sposób. Jeśli podczas wszczepiania bioproteza ulegnie 
zniszczeniu, nie należy podejmować próby jej naprawy.
NIE NALEŻY NARAŻAĆ bioprotezy na działanie jakichkolwiek roztworów, 
środków chemicznych, antybiotyków itp., z wyjątkiem jałowego 
roztworu soli fizjologicznej. Może nastąpić nienaprawialne uszkodzenie 
tkanki płatków, które może nie być widoczne gołym okiem.
NIE WOLNO CHWYTAĆ tkanki płatków bioprotezy narzędziami ani w 
żaden sposób uszkadzać bioprotezy. Nawet najmniejsza perforacja 
tkanki płatków może z czasem ulec powiększeniu, powodując znaczne 
upośledzenie czynności zastawki.

41
NIE NALEŻY STOSOWAĆ ZBYT DUŻEGO ROZMIARU. Stosowanie zbyt 
dużego rozmiaru może spowodować uszkodzenie bioprotezy lub 
miejscowe naprężenia mechaniczne, których efektem może być 
uszkodzenie serca, zniszczenie tkanki płatków, zniekształcenie stentu i 
przepływ fali zwrotnej przez zastawkę.
NIE PRZEPROWADZAĆ PRZEZ BIOPROTEZĘ CEWNIKÓW, wprowadzanych 
do żył elektrod stymulujących ani żadnych narzędzi chirurgicznych, z 
wyjątkiem lusterka chirurgicznego używanego do sprawdzania 
umieszczenia rozpórek i szwów. Pozostałe narzędzia chirurgiczne 
mogą spowodować uszkodzenie tkanki płatków.
Podobnie jak w przypadku każdego implantowanego przyrządu 
medycznego, istnieje ryzyko odpowiedzi immunologicznej u pacjenta. 
Do składników modelu 11000M należy stop metalu, który zawiera 
kobalt, chrom, nikiel, molibden, mangan, węgiel, beryl oraz żelazo. 
Należy zachować ostrożność u pacjentów z nadwrażliwościami na te 
materiały. Urządzenie zostało wytworzone bez lateksu, ale mogło być 
produkowane w środowisku zawierającym lateks.
5.	 Zdarzenia niepożądane
5.1	 Zaobserwowane zdarzenia niepożądane
Podobnie jak w przypadku wszystkich sztucznych zastawek serca, stosowanie 
zastawek tkankowych może wiązać się z poważnymi działaniami niepożądanymi, 
niekiedy prowadzącymi do zgonu.  Ponadto po upływie różnych okresów czasu 
(godzin lub dni) mogą występować zdarzenia niepożądane wynikające z 
indywidualnej reakcji pacjenta na wszczepione urządzenie lub fizycznych i 
chemicznych zmian jego komponentów, zwłaszcza pochodzenia biologicznego; 
mogą one powodować konieczność ponownej operacji i wymiany protezy.
Osierdziowa bioproteza mitralna Edwards model 11000M jest podobna w 
konstrukcji do bioprotez osierdziowych Carpentier-Edwards PERIMOUNT 
Magna Mitral Ease model 7300TFX.
Przeprowadzono trzy (3) wieloośrodkowe, nierandomizowane, prospektywne 
badania kliniczne, poza terenem Stanów Zjednoczonych, u pacjentów z 
zaimplantowaną bioprotezą osierdziową zastawki mitralnej model 6900.  
Trzystu jeden (301) pacjentów poddanych zostało izolowanej wymianie 
zastawki mitralnej (MVR), a 62 wymianie dwóch zastawek (DVR), przy czym 
zastawka aortalna była wymieniana na bioprotezę osierdziową PERIMOUNT 
firmy Carpentier-Edwards model aortalny.
W pierwszym badaniu bioprotezy wszczepiano w latach od 1984 do 1986, w 
drugim badaniu bioprotezy wszczepiano w latach od 1989 do 1994, w trzecim 
badaniu bioprotezy wszczepiano w latach od 1996 do 1997.  Stan pacjentów 
oceniano przedoperacyjnie, śródoperacyjnie, przy wypisywaniu ze szpitala, po 
1 roku i następnie corocznie.  Przez cały okres pooperacyjny notowano 
występowanie zdarzeń niepożądanych.
Tabela 3 przedstawia częstość obserwowanych zdarzeń wczesnych dla modelu 
6900 (≤ 30 dni w przypadku zdarzeń niepożądanych związanych z zastawką), 
liniowo przedstawia częstość zdarzeń późnych (> 30 dni po zabiegu) oraz 
aktuarialną częstość zdarzeń niepożądanych po 1 roku, 5 latach i 8 latach po 
zabiegu.  Częstości występowania zdarzeń niepożądanych pochodzą od 
363 pacjentów w dziewięciu ośrodkach.  Zbiorczy czas obserwacji wyniósł 
1100 pacjentolat ze średnim czasem obserwacji wynoszącym 3,0 roku 
(SD = 2,4 roku, zakres = 0 do 8,2 lat).  Przedoperacyjne i pochodzące z okresu 
operacji dane demograficzne pacjentów zostały przedstawione w tabelach 5 i 7.  
Wyniki dotyczące skuteczności operacji zostały przedstawione w tabelach 9 i 11.
Przeprowadzono jedno (1) wieloośrodkowe, nierandomizowane, prospektywne, 
międzynarodowe badanie kliniczne u pacjentów z zaimplantowaną bioprotezą 
osierdziową zastawki mitralnej Carpentier-Edwards PERIMOUNT Plus model 
6900P.  U stu siedemdziesięciu pięciu (175) pacjentów przeprowadzono zabieg 
izolowanej wymiany zastawki mitralnej (MVR), a u 34 pacjentów zabieg wymiany 
dwóch zastawek (DVR) z wymianą zastawki aortalnej na bioprotezę osierdziową 
zastawki aortalnej Carpentier-Edwards PERIMOUNT.  W tym badaniu implantacje 
przeprowadzano w latach 1999-2007.  Stan pacjentów oceniano przedoperacyjnie, 
śródoperacyjnie/przy wypisywaniu ze szpitala, po 1 roku, a następnie corocznie.  
Przez cały okres pooperacyjny notowano występowanie zdarzeń niepożądanych.  
Tabela 4 przedstawia częstość obserwowanych zdarzeń wczesnych dla modelu 
6900P (≤ 30 dni w przypadku zdarzeń niepożądanych związanych z zastawką), 
liniowo przedstawia częstość zdarzeń późnych (> 30 dni po zabiegu) oraz 
aktuarialną częstość zdarzeń niepożądanych po 1 roku i 5 latach po zabiegu.  
Częstości zdarzeń niepożądanych podano w oparciu o dane dotyczące dwustu 
dziewięciu (209) pacjentów z siedmiu ośrodków.  Łączny okres obserwacji wyniósł 
873,18 pacjentolat ze średnim okresem obserwacji 4,2 roku (SD = 2,3 roku, zakres 
= 0 do 8,2 lat).  Przedoperacyjne i pochodzące z okresu operacji dane 
demograficzne pacjentów zostały przedstawione w tabelach 6 i 8.  Wyniki 
dotyczące skuteczności operacji zostały przedstawione w tabelach 10 i 12.
5.2	 Możliwe zdarzenia niepożądane
Zdarzenia niepożądane potencjalnie związane z zastosowaniem bioprotez 
zastawek serca to:
• 
Dławica piersiowa
• 
Skazy krwotoczne związane z leczeniem przeciwzakrzepowym 
(koagulopatia)
• 
Zaburzenia rytmu serca
• 
Zablokowanie ujścia wieńcowego
• 
Zapalenie wsierdzia
• 
Niewydolność serca
• 
Niedokrwistość hemolityczna
• 
Hemoliza
• 
Krwotok
• 
Miejscowe i/lub uogólnione zakażenie
• 
Zawał mięśnia sercowego
• 
Niedopasowanie protezy do pacjenta (PPM)
• 
Usidlenie płatka zastawki (wklinowanie)
• 
Niestrukturalna dysfunkcja protezy
• 
Wytworzenie łuszczki
• 
Przeciek okołozastawkowy
• 
Niedomykalność protezy
• 
Strukturalne uszkodzenie protezy
• 
Zakrzepica protezy
• 
Udar mózgu
• 
Zaburzenia zakrzepowo-zatorowe
• 
Przemijające niedokrwienie mózgu (TIA)
Wymienione powikłania mogą prowadzić do:
• 
Powtórnego zabiegu operacyjnego
• 
Usunięcia zastawki
• 
Trwałej niepełnosprawności
• 
Zgonu

42
Inne zdarzenia niepożądane, związane z zastosowaniem osierdziowej 
bioprotezy zastawki mitralnej Carpentier-Edwards PERIMOUNT model 6900, 
zebrane w literaturze oraz pochodzące z doniesień otrzymanych z systemu 
obsługi reklamacji firmy Edwards Lifesciences obejmują: stenozę, 
niedomykalność niewydolnej zastawki, perforację komory wspornikami 
stentów, niesprawność zastawki z powodu odkształcenia implantu, pęknięcie 
ramy prowadnicy drucianej.
6.	 Badania kliniczne
Punktami końcowymi bezpieczeństwa uchwyconymi w badaniach 
prospektywnych były zdarzenia niepożądane; stosowano analizy krwi w celu 
potwierdzenia nieobecności lub obecności określonych zdarzeń niepożądanych.  
Wyniki bezpieczeństwa dla modelu 6900 zaprezentowano w tabeli 3, a dla 
modelu 6900P w tabeli 4.  Przedoperacyjne dane demograficzne pacjentów dla 
modelu 6900 zostały przedstawione w tabeli 5, a dla modelu 6900P w tabeli 6.  
Operacyjne dane demograficzne pacjentów, którym wszczepiono model 6900, 
podano w tabeli 7, a model 6900P – w tabeli 8.  Punktami końcowymi 
skuteczności były klasyfikacja funkcjonalna Nowojorskiego Towarzystwa 
Kardiologicznego (NYHA) i badania echokardiograficzne.  Podsumowanie 
wyników klasyfikacji zawarto w tabeli 9 dla modelu 6900 i tabeli 10 dla modelu 
6900P.  Wyniki badań echokardiograficznych podsumowano w tabeli 11 dla 
modelu 6900 i tabeli 12 dla modelu 6900P.
Brak danych klinicznych wskazujących na zwiększoną odporność osierdziowej 
bioprotezy mitralnej Edwards model 11000M na zwapnienie, w porównaniu do 
innych dostępnych na rynku bioprotez.
7.	 Indywidualizacja leczenia
Biorcy bioprotez zastawek serca powinni kontynuować leczenie 
przeciwzakrzepowe (z wyjątkiem przypadków, w których jest ono 
przeciwwskazane) w pierwszym okresie po wszczepieniu – w każdym 
przypadku według oceny lekarza.  Długoterminowe leczenie przeciwzakrzepowe 
i/lub przeciwpłytkowe należy rozważyć u pacjentów z czynnikami ryzyka 
zaburzeń zakrzepowo-zatorowych.
Ostateczną decyzję w sprawie opieki nad konkretnym pacjentem powinien 
podjąć personel medyczny oraz pacjent, w świetle wszystkich okoliczności 
dotyczących tego pacjenta (poz.  7).  Bioproteza jest zalecana do MVR u 
pacjentów w każdym wieku, którzy nie będą przyjmować warfaryny lub mają 
poważne przeciwwskazania medyczne do leczenia warfaryną.  Preferencje 
pacjenta to racjonalne kryterium przy wyborze operacji wymiany zastawki 
mitralnej oraz wyborze protezy mitralnej.  Mechaniczna proteza jest rozsądnym 
wyborem do MVR u pacjentów poniżej 65 roku życia, którzy nie mają 
przeciwwskazania do leczenia przeciwzakrzepowego.  Bioproteza jest rozsądnym 
wyborem do MVR u pacjentów poniżej 65 roku życia, którzy wybrali wymianę 
zastawki ze względów związanych ze stylem życia po szczegółowym omówieniu 
ryzyka leczenia przeciwzakrzepowego względem prawdopodobieństwa 
konieczności przeprowadzenia kolejnego zabiegu MVR (poz.  7).  
7.1	 Szczególne grupy pacjentów
Nie potwierdzono bezpieczeństwa ani skuteczności stosowania modelu 
bioprotez 11000M w następujących szczególnych populacjach, ponieważ nie 
przebadano ich w takich grupach:
• 
kobiety ciężarne;
• 
matki karmiące;
• 
pacjenci z nieprawidłowym metabolizmem wapnia (np. z przewlekłą 
niewydolnością nerek lub nadczynnością przytarczyc);
• 
pacjenci ze schorzeniami zwyrodnieniowymi aorty powodującymi 
powstawanie tętniaków (np.  martwica torbielowata błony środkowej, 
zespół Marfana);
• 
dzieci, młodzież lub młode osoby dorosłe.
Przestroga: Na podstawie doniesień w piśmiennictwie na temat zastawek 
tkankowych (poz.  9, 10, 11, 12 i 13) wydaje się występować zwiększony odsetek 
zwapnienia listków u pacjentów w wieku poniżej 20 lat.  Jeśli jest to możliwe, 
należy unikać powtarzanych dożylnych wstrzyknięć preparatów zawierających 
wapń w okresie pooperacyjnym, a u dzieci także nadmiernego spożycia mleka 
oraz nabiału.  Wyniki badań prowadzonych na zwierzętach (poz.  14) wskazują, 
że wysoki poziom wapnia w organizmie może prowadzić do wczesnego 
powstawania zwapnień.  
8.	 Informacja dla pacjenta
Po operacji zaleca się uważną i stałą obserwację lekarską (przynajmniej jedna 
wizyta rocznie), aby umożliwić rozpoznanie i właściwe leczenie powikłań 
związanych z bioprotezą, szczególnie wynikających z uszkodzenia materiału.  
Pacjentom z bioprotezą, którzy są w grupie podwyższonego ryzyka bakteriemii 
(np.  mają być poddani zabiegom stomatologicznym), warto doradzić 
profilaktyczną terapię antybiotykową.  Pacjentom należy doradzać, aby zawsze 
nosili przy sobie Kartę danych wszczepu oraz informowali pracowników służby 
zdrowia o posiadanym implancie przy zasięganiu porady lekarskiej.
9.	 Sposób dostarczania
9.1	 Opakowanie
Osierdziowa bioproteza mitralna Edwards model 11000M jest dostarczana w 
postaci jałowej i niepirogennej w opakowaniu tacowym z podwójną ochroną.  
Opakowanie tacowe z podwójną ochroną mieści się w torebce foliowej, która 
znajduje się w kartonie.
Każda bioproteza umieszczona jest w kartonie ze wskaźnikiem temperatury 
widocznym przez okienko na panelu bocznym.  Wskaźnik temperatury 
przeznaczony jest do umożliwienia identyfikacji produktów narażonych na 
przejściowe skrajne warunki temperaturowe.  W chwili otrzymania bioprotezy 
należy niezwłocznie sprawdzić wskaźnik i zapoznać się z etykietą kartonu, aby 
potwierdzić stan „Do wykorzystania”.  Jeśli stan „Do wykorzystania” nie jest 
oczywisty, nie należy używać bioprotezy i skontaktować się z lokalnym 
dostawcą lub przedstawicielem firmy Edwards Lifesciences w celu dokonania 
ustaleń dotyczących potwierdzenia zwrotu i wymiany.
Ostrzeżenie: Dokładnie sprawdzić bioprotezę przed implantacją pod 
kątem dowodów ekspozycji na skrajne temperatury lub innych 
uszkodzeń.
9.2	 Przechowywanie
Osierdziową bioprotezę mitralną Edwards model 11000M należy przechowywać 
w temperaturze 10°C do 25°C (50-77 °F), w torebce foliowej i kartonie, na półce.
10.	 Wskazówki dotyczące użycia
10.1	 Szkolenia lekarzy
Techniki wszczepiania niniejszej bioprotezy są zbliżone do technik stosowanych 
przy wszczepianiu innych stentowych bioprotez zastawki mitralnej.  Specjalne 
przeszkolenie lekarzy nie jest konieczne do wykonywania implantacji 
osierdziowej bioprotezy mitralnej Edwards model 11000M.
10.2	 Kalibrowanie
Przestroga: Do określania rozmiaru bioprotezy 11000M nie należy 
używać kalibratorów zastawkowych innych producentów ani 
kalibratorów przeznaczonych do innych protez zastawkowych firmy 
Edwards Lifesciences.
Przestroga: Sprawdzić kalibratory i rękojeści pod kątem zużycia, 
takiego jak stępienie, pękanie lub spękanie włoskowate. W razie 
zauważenia jakichkolwiek objawów zużycia kalibrator lub rękojeść 
należy wymienić.

43
Ostrzeżenie: Fragmenty rękojeści i kalibratorów nie są radiologicznie 
nieprzezroczyste i nie można ich lokalizować za pomocą zewnętrznego 
urządzenia obrazującego.
Sprawdzić, czy akcesoria zostały wyjałowione zgodnie z zalecanymi instrukcjami 
dostarczonymi z akcesoriami wielorazowymi.
Czarne znaczniki na krawędzi odpowiadają czarnym szwom znacznikowym na 
pierścieniu do wszywania.  Wyznaczają one przednią część pierścienia do 
wszywania bioprotezy, która powinna zostać umieszczona naprzeciw przedniej 
międzyspoidłowej części naturalnego pierścienia, aby objąć obszar odpływu z 
lewej komory.  Wysokość i lokalizacja wsporników stentów jest oznaczona na 
kalibratorze 1173R, aby pomóc w optymalnym wyrównaniu i osadzeniu.
Kalibratory są dostarczane z wstępnie przymocowanymi rękojeściami, które 
wydłużają rękojeść dla lepszego dostępu w przypadku trudnych warunków, 
głębokiej klatki piersiowej lub dostępu minimalnie inwazyjnego.  Przyłączenie 
do kalibratora rękojeści tylnej zapewnia nieograniczany wgląd przez cylinder do 
komory celem oceny struktur podzastawkowych.  Kalibratory 1173B i 1173R są 
oznaczone rozmiarem bioprotezy.
Krok
Postępowanie
1
Ustalanie wymiarów za pomocą kalibratora cylindra 
1173B:  
Aby ustalić wymiary za pomocą kalibratora cylindra 1173B, należy 
przełożyć część cylindryczną kalibratora przez pierścień zastawki 
mitralnej.  Upewnić się, że część cylindryczna jest położona 
bezpośrednio w płaszczyźnie pierścienia zastawki mitralnej.
HVT60
2
Ustalanie wymiarów za pomocą kalibratora 1173R:  
Aby ustalić wymiary za pomocą kalibratora 1173R, należy 
przeprowadzić część cylindryczną kalibratora przez pierścień 
zastawki mitralnej w taki sposób, aby końcówka kalibratora 
(symulująca część pierścienia do wszywania bioprotezy) 
spoczywała na górnej krawędzi pierścienia.
HVT61
Inne techniki, jak zastosowanie podkładek, fałdowanie (reefing) płatków lub 
zachowywanie mitralnego aparatu podzastawkowego mogą dodatkowo 
zmniejszać rozmiar pierścienia zastawki mitralnej, a tym samym rozmiar 
bioprotezy do wszczepienia (poz.  8).  Przy stosowaniu tych technik zaleca się 
ponownie określić rozmiar pierścienia dla uniknięcia wszczepienia zbyt dużej 
bioprotezy.  Spójna wydolność osierdziowych bioprotez mitralnych Edwards 
model 11000M czyni wszczepianie zbyt dużego rozmiaru protezy 
niepotrzebnym do osiągnięcia pożądanej wydolności hemodynamicznej u 
większości pacjentów (tabela 11 i 12).
Ze względu na elastyczne właściwości struna może zostać wydłużona przez 
system uchwytu Tricentrix podczas implantacji, jednak skurczy się po usunięciu 
uchwytu, chwytając płatki i zaburzając funkcję zastawki.  Kalibratory 1173B i 
1173R są wykonane z przezroczystego materiału, aby aparat podzastawkowy 
był widoczny podczas dobierania rozmiaru.  Należy upewnić się, że żadna ze 
strun nie znajdzie się na drodze rozpórek.
Przestroga: Przy stosowaniu technik zachowania aparatu 
podzastawkowego należy zachować szczególną ostrożność, aby nie 
doszło do uchwycenia strun ścięgnistych w rozpórce.
Ostrzeżenie: Unikać stosowania zbyt dużego rozmiaru bioprotezy. 
Stosowanie zbyt dużego rozmiaru może spowodować uszkodzenie 
bioprotezy lub miejscowe naprężenia mechaniczne, których skutkiem 
może być uszkodzenie serca, zniszczenie tkanki płatków, 
zniekształcenie stentu i przepływ fali zwrotnej.
10.3	 Instrukcje dotyczące manipulacji i przygotowania
Zaleca się przeprowadzenie szkolenia w miejscu pracy przed rozpoczęciem 
manipulacji i przygotowania osierdziowej bioprotezy mitralnej Edwards, model 
11000M.
Krok
Postępowanie
1
Przestroga: Nie otwierać opakowania osierdziowej 
bioprotezy mitralnej Edwards model 11000M przed 
upewnieniem się, że dojdzie do implantacji.
Ostrzeżenie: Nie otwierać torebki foliowej w polu 
jałowym. Torebka foliowa stanowi jedynie osłonę 
zabezpieczającą. Jedynie najbardziej wewnętrzne 
opakowanie tacowe można wprowadzać do pola 
jałowego.
Po wyborze odpowiedniego rozmiaru bioprotezy należy, poza 
polem jałowym, wyjąć z kartonu torebkę foliową.  Przed 
otwarciem należy sprawdzić, czy opakowanie nie jest 
uszkodzone i czy nie brakuje pieczęci lub czy nie są one 
uszkodzone.
2
Należy przytrzymać podstawę tacy zewnętrznej w pobliżu 
pola jałowego i oderwać pokrywę tacy zewnętrznej.

46
Krok
Postępowanie
12
Do każdego pierścienia do wszywania bioprotezy dołączona jest 
etykieta z numerem seryjnym.  Należy sprawdzić, czy numer 
seryjny jest zgodny z numerem na opakowaniu bioprotezy i kartą 
danych implantacji bioprotezy.  Etykiety nie należy odrywać od 
bioprotezy przed upewnieniem się, że dojdzie do wszczepienia.
Przestroga: W przypadku zauważenia jakiejkolwiek 
różnicy w numerze seryjnym należy zwrócić nieużywaną 
bioprotezę.
Przestroga: Należy zwrócić szczególną uwagę na to, aby 
podczas usuwania etykiety z numerem seryjnym 
uniknąć nacięcia lub rozerwania tkaniny pierścienia do 
wszywania.
Przestroga: By uniknąć uszkodzenia tkaniny pierścienia 
do wszywania, nie należy przeciągać supła szwu z 
etykietą z numerem seryjnym przez pierścień do 
wszywania.
13
Osierdziowa bioproteza mitralna Edwards model 11000M NIE 
WYMAGA PŁUKANIA przed implantacją.
Przestroga: Jeśli bioproteza zostanie wypłukana przed 
implantacją, należy ją utrzymywać w stanie nawodnienia 
jałowym roztworem soli fizjologicznej po obu stronach 
tkanki płatka przez pozostały czas trwania zabiegu 
chirurgicznego. Zaleca się przepłukiwanie co jedną lub 
dwie minuty.
Przestroga: Należy unikać kontaktu tkanki płatka z 
ręcznikami, płótnem i innymi źródłami materii pylastej, 
która może zostać przeniesiona na tkankę płatka.
10.4	 Implantacja urządzenia
Krok
Postępowanie
1
Chirurg powinien znać zalecenia dotyczące doboru rozmiarów 
oraz umiejscowienia protezy ponad pierścieniem (Patrz 10. 2 
Kalibrowanie).
Ze względu na złożoność i rodzaje operacji wymiany zastawki 
serca wybór techniki chirurgicznej, odpowiednio 
zmodyfikowanej zgodnie z wcześniej opisanymi 
Ostrzeżeniami, zależy od decyzji chirurga.  Zasadniczo należy 
wykonać następujące kroki:
1.	 Chirurgicznie usunąć zmienione chorobowo lub uszkodzone 
płatki zastawki i wszystkie związane z nią struktury 
konieczne do usunięcia.
2.	 Chirurgicznie usunąć wapń z pierścienia w celu 
zapewnienia odpowiedniego umieszczenia pierścienia do 
wszywania bioprotezy i niedopuszczenia do uszkodzenia 
delikatnej tkanki płatka.
3.	 Odpowiednio dobrać rozmiar.  Zmierzyć pierścień, 
posługując się wyłącznie modelami kalibratorów 
mitralnych 1173B i 1173R (Rysunki 1a-1b).
4.	 Prawidłowo osadzić protezę.
5.	 Założyć szwy z umieszczonym na miejscu uchwytem w celu 
zminimalizowania możliwości zapętlenia szwów lub 
uchwycenia strun ścięgnistych.
Krok
Postępowanie
6.	 Upewnić się, że nie nastąpiło uszkodzenie płatków 
bioprotezy podczas zakładania szwów i że nie występuje 
przeciek.
Przestroga: Podczas doboru wymiarów bioprotezy dla 
danego pacjenta należy wziąć pod uwagę jego wymiary 
anatomiczne, wiek i kondycję fizyczną, aby zmniejszyć do 
minimum możliwość uzyskania suboptymalnego wyniku 
hemodynamicznego. Jednak ostatecznego doboru 
bioprotezy w poszczególnych przypadkach powinien 
dokonać lekarz po starannym rozważeniu wszystkich 
zagrożeń i korzyści dla określonego pacjenta.
Przestroga: Przed implantacją protezy należy w 
dostatecznym stopniu usunąć złogi wapnia z pierścienia 
włóknistego u pacjenta, aby uniknąć uszkodzenia 
delikatnych płatków bioprotezy w wyniku ich kontaktu 
ze złogami wapnia. Należy wprowadzić kalibrator do 
pierścienia zastawki mitralnej. Cylinder kalibratora 
powinien zawsze mieścić się swobodnie w pierścieniu.
Przestroga: Do wyboru rozmiaru bioprotezy stosować 
wyłącznie kalibratory 1173B lub 1173R; inne kalibratory 
mogą prowadzić do wyboru niewłaściwej zastawki 
(patrz 1.2 Opis akcesoriów). Podobnie do innych 
bioprotez mitralnych, osierdziową bioprotezę mitralną 
Edwards model 11000M wszczepia się zazwyczaj za 
pomocą zakładkowych szwów materacowych. Zaleca się 
dokonanie pomiaru pierścienia po założeniu szwów, 
ponieważ mogą one zmniejszyć rozmiar bioprotezy 
przeznaczonej do wszczepienia.
2
Prawidłowe zorientowanie bioprotezy:
Przestroga: Rama prowadnicy drucianej bioprotezy 
model 11000M jest symetryczna, a trzy podpórki spoidła 
(rozpórki) są rozmieszczone w równych odstępach. 
Jednak pierścień do wszywania został tak 
zaprojektowany, aby można go było użyć w określonym 
położeniu bioprotezy. Obrębiona część pierścienia do 
wszywania, znajdująca się pomiędzy dwoma 
silikonowymi wybrzuszeniami, powinna być umieszczona 
naprzeciw przedniej międzyspoidłowej części pierścienia, 
obejmując drogę odpływu z lewej komory.
Kontrastujące szwy znacznikowe na pierścieniu do wszywania 
są przeznaczone do ułatwienia właściwego ułożenia i wskazują 
typową odległość międzyspoidłową.  Jednak odległość ta może 
różnić się u poszczególnych pacjentów.  Po lewej stronie, dwa 
sąsiadujące ze sobą czarne szwy wskazują miejsce, w którym 
powinien być wykonany pierwszy szew i odzwierciedlają 
spoidło przednie.  Po prawej stronie pojedynczy czarny szew 
wskazuje przybliżoną lokalizację spoidła tylnego.  Dzięki 
wykorzystaniu powyższych pomocy w ułożeniu trzeci element 
powinien w sposób naturalny wypaść w miejscu (lub w pobliżu) 
tylnego płatka.
Przestroga: Należy zwrócić szczególną uwagę, aby nie 
umieścić rozpórki na wprost drogi odpływu z lewej 
komory, ponieważ mogłoby to upośledzić 
długookresową wydolność hemodynamiczną.

47
Krok
Postępowanie
3
Założenie szwu:
Czarna linia prowadząca szew obiega pierścień do wszywania.  
Przy zakładaniu szwów na pierścieniu do wszywania można 
zredukować siły przesuwające pierścień przez rozmieszczanie 
szwów na wprost przez pierścień i w obszarze od linii 
prowadzącej szwy do zewnętrznej części pierścienia do 
wszywania.
Należy utrzymywać szwy naprężone podczas obniżania 
bioprotezy do pierścienia; minimalizuje to możliwość 
utworzenia się zapętleń szwu, które mogłyby uchwycić płatek.  
Wraz z w pełni wsuniętymi wspornikami stentu, gdy system 
uchwytu Tricentrix znajduje się na miejscu, pomaga to we 
wprowadzeniu szwów do ich właściwych pozycji poza 
rozpórkami oraz na pierścieniu do wszywania.
Przed zawiązaniem szwów należy usunąć rękojeść.  Rękojeść i 
niebieski adapter muszą zostać usunięte razem jako zespół.  
Utrzymać rozmieszczenie bioprotezy w obrębie pierścienia przez 
delikatne chwycenie uchwytu kleszczykami lub dłonią w 
rękawiczce i przecięcie zielonej nitki na niebieskim adapterze.  
Zestaw niebieskiego adaptera i rękojeści należy wyjąć w całości 
jako zespół.
CP1089-27
Adapter
4
Przestroga: Należy unikać zapętlenia lub uwięzienia 
szwu wokół otwartych elementów szkieletu, wolnych 
rozpórek lub wsporników spoideł bioprotezy, co 
mogłoby zakłócać prawidłowe działanie zastawki. Dla 
zminimalizowania ryzyka zapętlenia szwów należy 
koniecznie pozostawić uchwyt w sercu do momentu 
zakończenia szycia.
Jeżeli jednak pozostawienie uchwytu na miejscu ogranicza pole 
widzenia chirurga, wszystkie szwy przylegające do każdej z 
trzech rozpórek szkieletu muszą zostać związane przed 
przecięciem trzech zielonych nici utrzymujących uchwyt (w celu 
jego usunięcia).
Przestroga: Jeżeli szwy utrzymujące umieszczony uchwyt 
zostaną przecięte przed związaniem tych przylegających 
szwów, uchwyt nie będzie już minimalizować możliwości 
zapętlenia szwów wokół rozpórek szkieletu.
Krok
Postępowanie
Należy w szczególności uważać, aby nie zawiązać szwów na 
szczytach rogów szarych odnóg uchwytu.  Przed zawiązaniem 
każdego ze szwów trzeba sprawdzić płatki, utrzymując oba 
końce nici w stanie naprężenia.  Odkształcenie lub ruch płatków 
podczas tej czynności może świadczyć o zapętleniu szwu wokół 
rozpórki.  W żadnym momencie przed usunięciem uchwytu lub 
po jego usunięciu nie wolno zmniejszyć naprężenia nici, gdyż 
mogłoby to spowodować powstanie pętli na szwach i 
ewentualnie uwięzienie.  Zaleca się umieszczenie lusterka 
chirurgicznego za płatkami po usunięciu uchwytu, aby 
sprawdzić każdą rozpórkę i właściwe umieszczenie szwów.
Przestroga: Podczas zakładania szwów przerywanych 
istotne jest, aby uciąć nici blisko punktów wiązania i 
upewnić się, aby odsłonięte końcówki nici nie stykały się 
z tkanką płatków (poz. 8). 
System uchwytu Tricentrix usuwa się jako jedną część po 
zakończeniu zakładania szwów w następujący sposób:
CP1089-14
1.	 Należy przeciąć każdy z trzech (3) widocznych zielonych 
szwów, używając skalpela lub nożyczek wprowadzonych 
wyłącznie do kanału cięcia.  Nigdy nie wolno podejmować 
prób przecięcia szwów pod częściowo oddzielonym 
uchwytem, ponieważ część szwów mocujących może wpaść 
do komory serca.  Należy unikać przecięcia oraz uszkodzenia 
stentu lub tkanki płatków podczas przecinania szwów.
2.	 Po prawidłowym przecięciu wszystkich trzech (3) szwów 
mocujących należy usunąć z bioprotezy (jako jedną część) 
system uchwytu Tricentrix wraz ze szwami mocującymi, 
używając jałowych rękawic lub zabezpieczonych 
kleszczyków.
3.	 Po implantacji wyjąć i wyrzucić uchwyt.
10.5	 Czyszczenie i sterylizacja akcesoriów
Akcesoria do osierdziowej bioprotezy mitralnej Edwards, model 11000M, są 
pakowane oddzielnie.  Rękojeść model 1126 dostarczana jest w stanie jałowym i 
jest przeznaczona wyłącznie do jednorazowego użytku.  Rękojeści model 1111, 
1117 i 1173 oraz kalibratory model 1173B i 1173R są dostarczane w stanie 
niejałowym i przed użyciem trzeba je umyć i wyjałowić.  Należy wyczyścić i 
ponownie wysterylizować rękojeści, kalibratory, podstawę i pokrywę tacy przed 
każdym użyciem.  Instrukcje dotyczące mycia i wyjaławiania zawarte są w 
instrukcji stosowania dostarczanej z akcesoriami wielorazowymi.

50
Tabela 5: Przedoperacyjne dane demograficzne pacjentów (Model 6900)
Parametr
Kategoria
Charakterystyka badania (N = 363; łącznie 1100 pacjentolat)
n
% (n/N)1
Wiek w momencie wszczepienia (N = 363)
Średnia ± SD
66,1 ± 10,7
Płeć
Kobieta/mężczyzna
212/151
58,4%/41,6%
Rozpoznanie/etiologia
Brak
30
8,3%
Stenoza
91
25,1%
Niedomykalność
184
50,7%
Wada złożona
58
16,0%
Uwaga:
1.	 n = liczba pacjentów w każdej kategorii; N = liczba pacjentów w badaniu ogółem.
Tabela 6: Przedoperacyjne dane demograficzne pacjentów (Model 6900P)
Parametr
Kategoria
Charakterystyka badania (N = 209; łącznie 873,18 pacjentolat)
n
% (n/N)1
Wiek w momencie wszczepienia (N = 209)
Średnia ± SD
71,4 ± 9,4
Płeć
Kobieta/mężczyzna
138/71
66,0%/34,0%
Rozpoznanie/etiologia
Wada złożona
48
23,0%
Niedomykalność
121
57,9%
Stenoza
32
15,3%
Dysfunkcja zastawki
8
3,8%
Uwaga:
1.	 n = liczba pacjentów w każdej kategorii; N = liczba pacjentów w badaniu ogółem.

51
Tabela 7: Operacyjne dane demograficzne pacjentów (Model 6900)
Charakterystyka badania 
(N = 363; łącznie 1100 pacjentolat)
Parametr
Kategoria
n
% (n/N)1
Etiologia2
Choroba reumatyczna serca
135
37,2%
Zwapnienie
82
22,6%
Degeneracja
50
13,8%
Zapalenie wsierdzia
39
10,7%
Uszkodzenie bioprotezy
15
4,1%
Choroba niedokrwienna serca
14
3,9%
Nieprawidłowości wrodzone
8
2,2%
Inna
44
12,1%
Procedury towarzyszące2
Brak
200
55,1%
CABG3
78
21,5%
Zabieg naprawczy zastawki trójdzielnej
61
16,8%
Kontrapulsacja wewnątrzaortalna
17
4,7%
Rozrusznik4
6
1,7%
Zabieg naprawczy aorty/wymiana
5
1,4%
Zabieg naprawczy tętniaka
4
1,1%
Inna
31
8,5%
Występujące wcześniej schorzenia2
Brak
122
33,6%
CAD5/CABG
72
19,8%
Nadciśnienie
61
16,8%
Migotanie przedsionków
53
14,6%
Przebyty MI6
45
12,4%
Choroba naczyń mózgowych
36
9,9%
Inna
234
64,5%
Rozmiar zastawki (mm)
25
22
6,1%
27
110
30,3%
29
137
37,7%
31
81
22,3%
33
13
3,6%
Uwagi:
1.  	 n = liczba pacjentów w każdej kategorii; N = liczba pacjentów w badaniu ogółem
2.  	 Może być więcej niż jeden na pacjenta
3.  	 CABG = Coronary Artery Bypass Graft (Pomostowanie aortalno-wieńcowe)
4.  	 Utrwalone lub napadowe
5.  	 CAD = Coronary Artery Disease (Choroba wieńcowa)
6.  	 MI = Myocardial Infarction (Zawał serca)

52
Tabela 8: Operacyjne dane demograficzne pacjentów (Model 6900P)
Charakterystyka badania 
(N = 209; łącznie 873,18 pacjentolat)
Parametr
Kategoria
n
% (n/N)1
Etiologia2
Zwapnienie
38
18,2%
Wada wrodzona
1
0,5%
Zmiany zwyrodnieniowe
105
50,2%
Odległe następstwa zapalenia wsierdzia
10
4,8%
Niedokrwienne
12
5,7%
Reumatyczne
64
30,6%
Inna
36
17,2%
Procedury towarzyszące2
Brak
91
43,5%
Korekta zastawki/pierścienia włóknistego
3
1,4%
CABG3
58
27,8%
Stały stymulator serca
1
0,5%
Korekta zastawki trójdzielnej/pierścienia 
włóknistego
21
10,0%
Inna
78
37,3%
Występujące wcześniej schorzenia2
Brak
17
8,1%
Arytmie
95
45,5%
CAD4
85
40,7%
Kardiomiopatia
13
6,2%
Zastoinowa niewydolność serca
66
31,6%
Zapalenie wsierdzia
14
6,7%
Zawał mięśnia sercowego
21
10,0%
Choroba naczyń obwodowych
9
4,3%
Nadciśnienie płucne
66
31,6%
Gorączka reumatyczna
16
7,7%
Nadciśnienie uogólnione
49
23,4%
TIA5/CVA6
24
11,5%
Inna
35
16,7%
Rozmiar zastawki (mm)
25
28
13,4%
27
37
17,7%
29
84
40,2%
31
43
20,6%
33
17
8,1%
Uwagi:
1.  	 n = liczba pacjentów w każdej kategorii; N = liczba pacjentów w badaniu ogółem
2.  	 Może być więcej niż jeden na pacjenta
3.  	 CABG = Coronary Artery Bypass Graft (Pomostowanie aortalno-wieńcowe)
4.  	 CAD = Coronary Artery Disease (Choroba wieńcowa)
5.  	 TIA = przejściowy atak niedokrwienny
6.	 CVA = udar mózgu

53
Tabela 9: Skuteczność według kryterium klasyfikacji NYHA (Model 6900)
Klasa funkcjonalna NYHA
Ocena  
przedoperacyjna
Oceny pooperacyjne
1 do 2 lat
5 lat
n/N1
%
n/N
%
n/N
%
I
11/363
3,0
120/268
44,8
40/129
31,0
II
73/363
20,1
90/268
33,6
25/129
19,4
III
192/363
52,9
15/268
5,6
1/129
0,8
IV
84/363
23,1
0/268
0,0
0/129
0,0
Niedostępne
3/363
0,8
43/268
16,0
63/129
48,8
Uwaga:
1.  	 n = liczba pacjentów w każdej kategorii; N = liczba pacjentów w badaniu ogółem.
Tabela 10: Skuteczność według kryterium klasyfikacji NYHA (Model 6900P)
Klasa funkcjonalna NYHA
Ocena  
przedoperacyjna
Oceny pooperacyjne
1 rok
5 lat
n/N1
%
n/N
%
n/N
%
I
6/209
2,9
86/187
46,0
30/96
31,3
II
27/209
12,9
68/187
36,4
33/96
34,4
III
121/209
57,9
8/187
4,3
6/96
6,3
IV
55/209
26,3
1/187
0,5
0/96
0,0
Niedostępne
0/209
0,0
24/187
12,8
27/96
28,1
Uwaga:
1.  	 n = liczba pacjentów w każdej kategorii; N = liczba pacjentów w badaniu ogółem.

58
This page intentionally left blank. n Cette page est intentionnellement laissée blanche. n Niniejsza strona pozostaje pusta. 

EDWARDS LIFESCIENCES LLC 
CLINICAL INVESTIGATIONAL PLAN 
PROTOCOL NUMBER: 2012-02 
 
ATTACHMENTS 
 
CONFIDENTIAL AND PROPRIETATARY DATA: This document and the information contained herein may not be reproduced, used, or disclosed 
without written permission from Edwards Lifesciences LLC 
REVISION J: 03 MARCH 2021 
 
 
 
 
ATTACHMENT C – INFORMED CONSENT FORM TEMPLATE 
 

Sample Informed Consent 
Page 1 
SAMPLE INFORMED CONSENT – Model 11000A 
Subject Information 
CLINICAL TRIAL # 2012-02 (AORTIC CONSENT FORM, CONTINUED FOLLOW-UP) 
ProspeCtive, nOn‐randoMized, MulticENter Clinical evaluation of the Edwards Pericardial Aortic 
& Mitral Bioprostheses (Models 11000A and 11000M) with a new tissue treatment platform 
(COMMENCE TRIAL) 
You are invited to take part in a clinical research trial.  This information sheet tells you why the 
research is being done and what it would involve for you if you chose to take part.  Please read 
the following information carefully and feel free to discuss this with your family or your doctor.  
If you are unclear about anything or would like more information, please contact, <Name> on 
<Tel. number>. Give yourself time to decide whether or not you wish to take part.  Your 
participation in this research trial is voluntary.  If you decide to participate, we will ask you to sign 
this document in order to state your agreement.  This trial is given a favorable opinion by the 
Institutional Review Board and by the US Food and Drug Administration (FDA).  It will be 
conducted according to the regulations governing clinical research.  A description of this clinical 
trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This Web site will 
not include information that can identify you. At most, the Web site will include a summary of 
the results. You can search this Web site at any time.  
Introduction 
The heart contains four (4) valves, which allow the blood to flow in the correct direction.  When 
a valve does not work properly, the heart has to work harder in order to pump the required 
amount of blood to the body.  This may cause symptoms that depend on the valve that is 
damaged and the amount of the damage. If the damage is serious, surgery to remove and replace 
the damaged valve with a new valve is recommended. 
What is the purpose of this trial? 
The objective of this trial is to confirm that modifications to tissue processing, valve sterilization, 
and packaging of the FDA-approved (P860057/S042) Carpentier-Edwards PERIMOUNT Magna 
Ease Pericardial Bioprosthesis, Model 3300TFX (designated as the Edwards Pericardial Aortic 
Bioprosthesis, Model 11000A) do not raise any new questions of safety and effectiveness in 
subjects who require replacement of their native or prosthetic aortic valve. The only differences 
between the Model 3300TFX and the Model 11000A are modifications in tissue processing, valve 
sterilization, and packaging. Data collected in this clinical investigation was submitted to the FDA, 
and the Model 11000A valve is now approved to sell in the United States. In order to obtain 
sufficient long-term data on the valve, up to 250 Subjects at up to 10 hospitals that consent to 
extended follow-up will continue  to be followed in this trial for up to 10 years (an additional 5 
years from original study design). 
Why am I asked to participate to this research trial? 
You are being asked to continue to participate in this trial because continued follow up beyond 
the original 5 year duration is a request by the FDA so that Edwards may obtain long term 

Sample Informed Consent 
Page 2 
performance data on the valve that you received. This new aortic valve was developed to treat 
subjects having aortic valve disease like you. 
Trial design  
Up to 700 aortic valve replacement subjects and up to 175 mitral valve replacement subjects in 
up to 40 hospitals located throughout the United States, Canada, Europe and Asia Pacific will be 
enrolled in this trial. Your participation in this trial will not change your planned surgical 
treatment as all enrolled subjects will receive the Model 11000A valve, unless contraindicated by 
the trial doctor. The entire length of the trial is expected to last up to 10.5 years. Your 
participation will last for 10 years. You will be asked to return to the hospital where the surgery 
was done and be checked by the trial doctor or his/her colleagues.  You will be assessed at 
discharge, 1 month, at 3 months, 12 months, and annually thereafter for 10 years from the time 
of implant of the Model 11000A valve into your heart.  Please note the 1 month visit will be 
conducted by phone. 
 
Description of the Edwards Pericardial Aortic Bioprosthesis, Model 11000A  
The Edwards Pericardial Aortic Bioprosthesis, Model 11000A is an FDA-approved device.  The 
Model 11000A valve is an FDA-approved Carpentier-Edwards PERIMOUNT Magna Ease 3300TFX 
valve, with modifications in tissue processing, valve sterilization, and packaging.   
The Magna Ease valve consists of three tissue leaflets made of bovine (cow) pericardium (heart 
tissue). These leaflets have been treated with a new Edwards tissue process, built on the FDA-
approved Edwards ThermaFix process to stabilize and preserve tissue. This process also allows 
the Model 11000A to be stored in non-liquid packaging and to not require rinsing prior to implant.  
How was the valve under investigation tested? 
The valve was tested, on animals and in bench-top laboratory testing, in conformity with the U.S. 
Regulations. The valve also has been implanted in 133 patients in Europe. Preliminary results of 
these tests to date have shown that the valve is suitable for implant in humans. 
The technique used for implanting the valve is the same as your doctor uses with other biological 
heart valves. Each of the trial doctors involved in this clinical trial is properly trained on how to 
implant the Model 11000A valve. 
The Model 11000A valve is being tested in ongoing clinical trials inside and outside the United 
States. 
What will happen to me if I take part? 
If you agree to participate in this trial, you will be treated like any other subject having a similar 
operation and you also will have some more tests (described below) to collect more information 
about the valve and the surgery. 
The decision about participating in this trial is entirely yours.  Please make sure that all your 
questions are addressed before you make a decision.  If you consent to participate, we will ask 
you to sign and date this informed consent form.  A copy of this form will be given to you.  

Sample Informed Consent 
Page 3 
The trial doctor will then ask you questions and will run tests and procedures to see if you qualify 
for trial participation. These tests and procedures include: 
• Your blood pressure, heart rate, height, and weight will be measured (physical exam) 
• Your medical history and your current medications will be reviewed  
• Your blood will be collected for laboratory testing.  The blood draw will consist of a needle 
being stuck into a vein in your arm (or other area where a vein can be accessed).  
Approximately two tablespoons (30 mL) of blood will be drawn at this visit for routine 
tests including a complete blood count, plasma free hemoglobin, or haptoglobin or serum 
LDH, coagulation profile, and serum creatinine to test for kidney function.  Any remaining 
blood sample will be discarded according to hospital regulations. 
• An electrocardiogram (a test using a machine that records the electrical activity of your 
heart. The recording is done by putting self adhesive discs on your chest) 
• An echocardiogram (a test using a machine that creates sound waves creating pictures of 
inside your heart. A small probe is put on the outside of your chest) 
• The severity of your health will be graded using a standard scale by the New York Heart 
Association (NYHA) based on your ability to do physical activities 
• You will complete a questionnaire to assess your quality of life 
• If you are a woman of child-bearing age (and are not sterile) a small amount of blood or 
urine will be obtained to check for pregnancy 
If the results of the tests and examinations do not meet the trial requirements and your doctor 
assesses that you are not qualified to participate in the trial, you will be excluded from the trial 
and the trial doctor will discuss with you an alternative treatment for your disease.  No further 
commitments related to this trial will be requested from you. 
If, as a result of the above mentioned tests and examinations, your doctor assesses that you are 
qualified to participate in the trial, you will be scheduled for surgery. Upon your approval, your 
personal physician will be informed of your participation in the clinical trial. 
Similar to other aortic valve replacement operations, this surgical procedure is performed under 
general anesthesia.  The cardiac surgeon reaches the heart by making a cut in the chest and 
opening the sternum [breast bone].  The beating of the heart is stopped and the blood circulation 
will continue using a “heart-lung” machine.   
If during surgery your trial doctor finds a reason not to implant the Model 11000A valve, you will 
receive an FDA-approved aortic valve. You will not have any further commitments related to this 
trial. 
If your trial doctor determines that there are no contraindications, you will receive the Model 
11000A valve and you will be considered enrolled in the trial.  
During your surgery after the Model 11000A valve is implanted, a small tube used as a probe for 
a transesophageal echocardiogram (TEE) will be entered through your mouth and advanced 
down to the area of the heart.  The doctor will use this echocardiogram to take pictures of your 
heart.  This is part of every surgery to replace a heart valve.  
If the Model 11000A valve is replaced with another FDA-approved aortic valve at any time after 
enrollment, you will be followed for 30 days or until any symptoms or side effects you may 

Sample Informed Consent 
Page 4 
experience have resolved. Your investigational valve may be removed or explanted and sent to 
the Sponsor or an independent lab for further analysis. 
After your surgery and before you go home, you will have some more tests and examinations as 
described below: 
• Your blood pressure, heart rate and weight will be measured (physical exam) 
• Your current medications will be recorded  
• Blood tests (including a complete blood count, plasma free hemoglobin or haptoglobin or 
serum LDH and coagulation profile) 
• An electrocardiogram (once right after your procedure, and once before you go home) 
• An echocardiogram will be obtained to see that the newly implanted Model 11000A valve 
sits well in its position and that it works well 
• You will be asked if you have experienced any unusual symptoms or side effects since the 
procedure – any finding will be recorded in order to control your health status 
 
At 1 month after your surgery, you will be called and asked to provide information about your 
health status: 
• Your current medications will be recorded 
• Your health condition will be graded based on your ability to perform physical activities 
(NYHA class) 
• You will be asked if you have experienced any unusual symptoms or side effects since 
your last assessment 
• An appointment will be scheduled for you to return to the trial center approximately at 3 
months from your procedure date 
 
During your 3 month and subsequent annual follow-up visits, you will be asked to provide 
information about your health status and you will undergo the following procedures: 
• Your blood pressure, heart rate and weight will be measured (physical exam) 
• Your current medications will be recorded 
• Blood tests (including a complete blood count, plasma free hemoglobin or haptoglobin or 
serum LDH, and coagulation profile)  
• An electrocardiogram  
• An echocardiogram  
• Your health condition will be graded based on your ability to perform physical activities 
(NYHA class) 
• You will complete a questionnaire that will help your doctor to assess your quality of life 
(only at 12 month follow-up) 
• You will be asked if you have experienced any unusual symptoms or side effects since 
your last assessment 
 
 
Participant responsibilities 

Sample Informed Consent 
Page 5 
If you decide to participate in this research trial, you will have to follow the instructions given by 
your trial doctor and his colleagues and return to the hospital for all the follow-up visits until the 
tenth follow up year. Completing all trial visits is important to make sure that the trial results are 
complete and accurate. If you wish to stop participating in the trial or if you find you have not 
followed instructions listed above, it is important that you notify the trial doctor or research staff. 
Your participation in this research trial is entirely voluntary and it is your right to refuse to 
participate or withdraw at any time without penalty or loss of benefits to which you are otherwise 
entitled.  You are free to withdraw from the trial at any time without giving any reason, even if 
you have confirmed in writing that you want to take part.  Your decision to withdraw will not 
have any adverse effect whatsoever on your further treatment in our hospital. 
Giving false, incomplete, or misleading information about your medical history, including past 
and present use of medications, could have a very serious effect on your health.  It is very 
important that you give a true and complete medical history. 
What are the possible benefits of taking part? 
There are no guaranteed benefits from participation in this clinical investigation.   
 
Potential benefits resulting from this clinical trial include:  
• improvement of aortic valve function 
• acute relief of symptoms related to aortic stenosis 
• improvement in morbidity and mortality compared to similar/conventional devices  
 
In addition, information gained from the conduct of this trial may be of benefit to other people 
with the same medical condition in the future. The long-term results of using the investigational 
valve are not known at the present time.  
 
Alternative treatments include palliative medical therapy, aortic balloon valvuloplasty (opening 
the narrowed aortic valve with a balloon catheter) and surgical replacement of the aortic valve 
with another brand of prosthesis. 
What are the possible risks/inconveniences of taking part? 
You must understand that the treatment of choice for your condition is a heart valve replacement 
and that alternative valves are available.  
As with all prosthetic heart valves, there is a possibility that serious complications, sometimes 
leading to death, could develop that were not anticipated. In addition, complications and 
inconveniences due to individual subject reaction to an implanted device, or to physical or 
chemical changes in the components, particularly those of biological origin may occur, 
necessitating reoperation and replacement of the prosthetic device. These risks will be explained 
to you by your trial doctor. Unforeseeable risks may also occur.  Should any side effects occur, 
they will be fully assessed and you will be monitored closely.  
You may experience events and/or outcomes that may include, but are not necessarily limited 
to, the following: 
 

Sample Informed Consent 
Page 6 
Known/potential risks associated with the use of stented bioprosthetic heart valves include but 
are not limited to:  
 
 
Angina (chest pain or other pain 
from the heart) 
 
Bleeding diatheses/coagulopathy 
related to anticoagulant therapy 
(increased susceptibility to bleeding) 
 
Cardiac arrhythmias (change in or 
blockage of the heartbeat rhythm) 
 
Cardiac failure 
 Coronary ostial blockage (blockage 
of opening of coronary artery) 
 Endocarditis (infection of the valve) 
 
Hemolysis/Hemolytic anemia 
(breaking open of red blood cells 
with release of hemoglobin) 
 
Hemorrhage (bleeding) 
 
Immunological response 
 
Leaflet entrapment (impingement) 
 
Myocardial infarction (heart attack) 
 
Nonstructural valve dysfunction 
 
Malfunctions 
of 
valve 
due 
to 
distortion at implant, fracture of 
wireform, physical and or chemical 
deterioration of valve components 
 
Paravalvular/Perivalvular leak (blood 
leaking around the valve when it is 
closed) 
 
Patient prosthetic mismatch (PPM) 
(inappropriate sizing) 
 
Regurgitation/insufficiency (blood 
leaking through the valve when it is 
closed) 
 
Stenosis (narrowing of the valve) 
 
Thromboembolism/stroke 
(blood clot breaking off from the 
valve and causing blockage in the 
circulation downstream) 
 
Tissue 
deterioration 
including 
infection, calcification, thickening, 
perforation, degeneration, suture 
abrasion, instrument trauma, and or 
leaflet detachment 
 
Transient ischemic attack (TIA) 
(mini-stroke) 
 
Valve pannus  (excessive tissues 
growth around the valve) 
 
Valve thrombosis (blood clot 
attachment to the valve) 
 
 
Potential risks associated with aortic valve replacement surgery include but are not limited 
to: 
 
 
Allergic reaction  
 
Annular dissection (tear in the tissue 
around valve opening) 
 
Aortic/arterial dissection (tear in the 
artery) 
 
Bleeding, anticoagulant related 
(related to blood thinners) 
 
Bleeding, procedural/post-
procedural (during or after surgery) 
 
Cardiac arrest (heart stops beating) 
 
Cardiogenic shock (not enough 
blood being pumped by the heart) 
 
Disseminated intravascular 
coagulation (DIC) (the blood clots 
too much) 
 
Esophageal rupture (tear or hole in 
the tube that connects the mouth to 
the stomach) 

Sample Informed Consent 
Page 7 
 
Heart failure 
 
Hematoma (localized collection of 
blood) 
 
Heparin induced thrombocytopenia 
(HITs) (low platelet count in blood 
due to medication) 
 
Hypertension/Hypotension (blood 
pressure that is too low or too high) 
 
Hypoxemia (lack of oxygen) 
 
Infection, local or wound 
 
Infection, systemic (body-wide, 
called septicemia) 
 
Myocardial Infarction (heart attack) 
 
Multi-system organ failure (MOF) 
(example liver and or kidneys stop 
working) 
 
Pericardial effusion (fluid around the 
heart) 
 
Pericardial tamponade (a large 
amount of fluid around the heart 
such that is interferes with its 
normal performance) 
 
Pleural effusion (fluid around the 
lungs) 
 
Pulmonary edema (fluid in the lungs) 
 
Pneumonia (infection of the lungs) 
 
Renal dysfunction (kidney function 
worsening) 
 
Respiratory failure (lung failure 
where the level of oxygen in the 
blood becomes dangerously low) 
 
Thromboembolism (blood clot) 
– Venous, peripheral or central 
(blood clot in vein) 
– Arterial, peripheral or central 
(blood clot in artery) 
– Pulmonary, thrombus (blood clot 
in lung)
 
These complications may manifest clinically as symptoms including but not limited to abnormal 
heart murmur, exercise intolerance, shortness of breath, anemia, and/or fever. 
It is possible that these complications could lead to:  
• 
Reoperation 
• 
Explant (removal of the valve) 
• 
Permanent disability 
• 
Death 
 
Risks associated with the Model 11000A are anticipated to be the same as listed above for other 
aortic bioprosthetic valves and valve replacement surgery. 
You may require anti-coagulant therapy (a substance that prevents clotting of the blood) as a 
result of having your aortic valve replaced with the Model 11000A valve.  You may require long-
term anti-platelet therapy (aspirin, unless there is a reason you should not take it) even if long-
term anti-coagulant therapy is not required. 
Post procedural anti-coagulant and anti-platelet medications include the risk of causing severe 
bleeding and heavy blood loss. Because of this risk, anyone taking these drugs must take care to 
avoid injuries. Any falls, blows to the body or head, or other injuries should be reported to a 
physician, as internal bleeding may occur without any obvious symptoms.  Post procedural anti-
coagulation and associated risks are no different with the investigational valve than with valves 
already approved by the FDA. 
 

Sample Informed Consent 
Page 8 
Risks from taking a blood sample 
You will have routine blood samples taken from a vein in your arm by a needle stick.  Risks 
associated with drawing blood from your arm include slight discomfort and/or bruising.  
Infection, bleeding, clotting, or fainting also are possible, although unlikely.  The number of times 
that you will have a blood sample drawn for this trial is maximal 8 times over approximately 5 
years.  At maximum, two tablespoons (30 mL) of blood will be taken at a single visit.   
 
Risks from an electrocardiogram 
In rare circumstances, a rash or irritation at the location of the electrocardiogram electrode 
placement can occur due to the adhesive.  If this should occur, it will be assessed and treated 
using clinical standards of care with appropriate medication(s) and/or compresses. 
 
Risks from an echocardiogram 
A lubricant (gel) is used on the skin to improve picture quality and this may feel cold.  There are 
no known risks associated with receiving a transthoracic echocardiogram. 
Risks from an transesophageal echocardiography (TEE) 
The few risks of TEE involve passing the probe from your mouth down into your throat and 
esophagus. You may have a sore throat for a day or two. In very rare cases, TEE causes the 
esophagus to bleed. 
If I decide against participating in the clinical trial what other options do I have? 
If you decide not to participate in this trial, you can discuss with your doctor which options of 
heart valve replacement best suit your requirements.  There are a number of brands of 
bioprosthetic valves available.  Alternatives available to you may include continuation of your 
current heart medications and treatments without having surgery to replace your aortic valve.  It 
is important that you discuss these other options with your doctor. This does not in any way 
affect your further clinical care.  
What if something goes wrong? 
Your doctor and Edwards Lifesciences LLC will take all appropriate efforts to prevent any injury 
or illness which may occur as a result of your participation in this trial.  If you suffer any injury or 
illness as a direct result of participating in this trial, you will receive medical care and treatment 
at this hospital. Call your trial doctor immediately. Signing this consent does not affect any legal 
rights you have.  
Will my taking part in this trial be kept confidential? 
The records of this trial will be kept confidential. This section explains how your medical records 
might be used and disclosed if you agree to participate in this trial. 
All physicians involved in the trial follow a strict clinical protocol. You have the right to determine 
who has access to your health records.  Records collected in this trial includes your medical 
history, the results of physical exams, lab tests and other diagnostic procedures as described 

Sample Informed Consent 
Page 9 
above in this consent form, as well as basic demographic information and data related to your 
trial treatment. 
By signing this form: 
• You allow the research staff and/or the trial doctor to use your medical records for the 
trial and to disclose your health information to the Sponsor, Edwards Lifesciences LLC, or 
to the sponsor’s representatives, in order to review the results of the trial and to monitor 
the safety of participants. 
• You allow the trial doctor and/or sponsor to publish the results of the trial or discuss the 
results at conferences. If this is done, no information will be included that would reveal 
your identity. 
The information sent by the trial doctor and/or research staff to the Sponsor will not include your 
name, address, or other identifiers.  Instead, the trial doctor will assign a coded number to the 
records that are provided to the Sponsor.  However, your entire medical record may be reviewed 
at the trial doctor’s office and/or hospital by the Sponsor and/or Sponsor representatives, by 
regulatory/government agencies including the Food and Drug Administration (FDA) and the 
independent Institutional Review Board (IRB - a committee formally selected to approve, review 
and monitor research involving human subjects), and/or other regulatory agencies in other 
countries. The purpose of these reviews is to assure the safety and well-being of trial participants 
and the quality of the clinical trial. 
The trial doctor and/or research staff will make every effort to protect the privacy of your 
information.  However, absolute confidentiality cannot be guaranteed because of the need to 
disclose information as described above.   
This authorization does not have an expiration date.  If you do not cancel this authorization then 
it will remain in effect indefinitely. 
You can cancel this authorization at any time by giving a written notice to the trial doctor.  If you 
cancel this authorization, then you no longer will be able to participate in the trial, and the 
information that was collected prior to canceling the authorization may still be used and disclosed 
to the above-mentioned parties.  You will receive a signed copy of this consent for your records. 
All data collected within the scope of the trial may be forwarded to other persons or institutions 
not authorized for direct data inspection in an anonymized form only. 
Participation and Withdrawal 
You have the right to choose not to be in this trial or to stop being a part of this trial at any time 
without any consequences. This means that there will be no penalty or loss of medical benefits 
to which you are entitled. 
If you choose to stop being a part of this trial, you must first notify the trial doctor immediately 
so that a plan can be provided for your continued medical care.  At the time you stop taking part 
in the trial, you will be asked to return for a final safety evaluation that will include gathering 
information about your current medical condition and conducting any required procedures. For 
your own safety, you should go through the trial exit procedures any time you leave the trial and 
make arrangements for your continued medical care. 
It is possible that your participation in this trial may be stopped at any time without asking you.  
This might happen if you do not follow the instructions given by the trial doctor or if the trial 

Sample Informed Consent 
Page 10 
doctor believes it is in your best interest.  The trial also may be stopped for administrative, 
medical, or other reasons as determined by the trial doctor, the Sponsor, or regulatory 
authorities.  Any significant new findings developed during the course of this research that might 
affect your willingness to participate in the trial will be provided to you and the trial doctor. 
While participating in this trial, you should not take part in any other clinical trial.  This is to 
protect you from possible injury that may arise. 
Who is organizing and funding the research? 
This trial/research is organized by Edwards Lifesciences LLC, the Sponsor and the company that 
makes the Model 11000A valve. The clinical research staff will not be paid to include you in this 
trial but the hospital will be reimbursed for the costs incurred in conducting this research. 
Costs and Compensation 
You will be billed for all charges normally associated with heart valve replacement (including trial-
related visits) – only those required procedures outside of the routine standard of care will be 
paid for by the sponsor. There will be no financial compensation for your participation in this 
clinical trial.   
You will be reimbursed for the travel expenses you have in order to return to the hospital for the 
follow-up visits required during the trial. You will still be responsible for the cost of your usual 
ongoing medical care, including procedures and/or non-trial drugs that are not required by this 
clinical research trial.  If you have any questions, please ask the trial doctor, or a member of the 
research staff. 
You understand that all forms of medical diagnosis and treatment, whether routine or trial-
related, involve some risk of injury. In spite of all precautions, you might develop medical 
complications from participating in this research trial. You understand that the Sponsor or the 
hospital cannot assume liability for injury caused by the use of this particular valve or any other 
valve. In the event physical injury occurs as a result of participating in this research trial, the 
necessary facilities, emergency treatment and professional medical services will be available to 
you, just as they are to anyone. In the event of an unexpected injury directly related to the 
investigational device or the procedures described in the Clinical Research Protocol, the 
Sponsor will reimburse the hospital for the cost of treatment for any such injury, under the 
following conditions: 
• The costs of treatment are not paid for by your medical or hospital insurance or 
coverage; and 
• The injury is not due to negligence of the Investigator or the hospital; 
• The Investigator and the hospital have followed the Clinical Protocol 
requirements; and  
• You have followed the instructions of the Investigator  
You further understand that you do not waive any liability rights for personal injury by signing 
this form. 
Contact details for further information 

Sample Informed Consent 
Page 11 
If you require any further information before or during the trial, or if you have any questions after 
you have read this Subject Information Sheet/ Informed Consent, please contact the trial doctor 
responsible for you: 
Trial Doctor: ____________________________ 
 
Phone: ______________ 
Further information 
You consent to participate in a research trial and your data will be used in the statistical analysis 
of that clinical trial. It is understood that your personal identifiable data continues to be subject 
to data protection and shall not be disclosed to any third parties. Participation in this clinical 
trial is voluntary, and you can discontinue participation at any time without giving reasons, and 
without penalty. The Principal Investigator or the Sponsor also may decide on your premature 
discontinuation in this trial. 
Signature of subject or his/her legal representative 
I have received written information about the clinical trial or the information was read out to me 
and I had sufficient time to read this through and think about it.  I also was orally informed in 
detail by _____________________________ (name of clinical investigator) about the nature, 
significance and scope of the clinical trial; in particular about the objectives, conduct, benefit, 
risk, and insurance coverage including the associated obligations. All my questions were 
answered in an understandable way.  I do not have any further questions right now. I know that 
I can ask questions at any time, including during and after the clinical trial. 
• I declare my voluntary consent to the clinical trial. I am aware that I can refuse to participate 
or withdraw my consent at any time without incurring any penalties or disadvantages. 
• I agree that my medical data may be recorded in the context of this clinical trial.  I agree that 
the medical data may be forwarded in anonymous form to authorized specialists for data 
processing and scientific evaluation and to the competent authorities for review. 
• At the same time, I agree that my health data may be recorded in the context of this clinical 
trial and representatives of the Sponsor or the regulatory agencies may inspect my data for 
review purposes. 
• Finally, I agree to scientific publication of the research results in compliance with provisions 
of data protection legislation. 
 
_____ I agree / _____ I do not agree that my primary care physician may be informed about my 
participation in this trial. 
 
 
 
 

Sample Informed Consent 
Page 12 
Print name of trial participant 
 
 
Date 
 
Time1 
Signature of trial participant 
 
 
 
 
 
 
 
 
 
 
Print name of legal representative (if 
required) 
 
Date 
 
Time 
 
 
 
 
 
 
Signature of legal representative 
(if required) 
 
 
 
 
Signature of Person Obtaining Consent 
I have explained the clinical trial to the subject or his/her legal representative and answered all 
his/her questions. I have the impression that he/she understands the information contained in 
this document and gives his/her consent to participate on his/her own free will. The subject was 
given a copy of the signed consent form. 
 
Name of  Person Obtaining Consent 
(printed) 
 
Date 
 
Time 
 
 
 
Signature of Person Obtaining 
Consent 
 
Clinic 
 
 
1 Required only if consent is taken on the same day as the trial procedure 
 

Sample Informed Consent 
Page 1 
SAMPLE INFORMED CONSENT- Model 11000M 
Subject Information 
CLINICAL TRIAL # 2012-02 (MITRAL CONSENT FORM, CONTINUED FOLLOW-UP) 
ProspeCtive, nOn‐randoMized, MulticENter Clinical evaluation of the Edwards Pericardial Aortic 
& Mitral Bioprostheses (Models 11000A & 11000M) with a new tissue treatment platform 
(COMMENCE TRIAL)  
You are invited to take part in a clinical research trial.  This information sheet tells you why the 
research is being done and what it would involve for you if you chose to take part.  Please read 
the following information carefully and feel free to discuss this with your family or your doctor.  
If you are unclear about anything or would like more information, please contact, <Name> on 
<Tel. number>. Give yourself time to decide whether or not you wish to take part.  Your 
participation in this research trial is voluntary.  If you decide to participate, we will ask you to sign 
this document in order to state your agreement.  This trial is given a favorable opinion by the 
Institutional Review Board and by the US Food and Drug Administration (FDA).  It will be 
conducted according to the regulations governing clinical research.  A description of this clinical 
trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This Web site will 
not include information that can identify you. At most, the Web site will include a summary of 
the results. You can search this Web site at any time.  
Introduction 
The heart contains four (4) valves, which allow the blood to flow in the correct direction.  When 
a valve does not work properly, the heart has to work harder in order to pump the required 
amount of blood to the body.  This may cause symptoms that depend on the valve that is 
damaged and the amount of the damage. If the damage is serious, surgery to remove and replace 
the damaged valve with a new valve is recommended. 
What is the purpose of this trial? 
The objective of this trial is to confirm that modifications to tissue processing, valve sterilization, 
and packaging of the FDA-approved (P860057/S068) Carpentier-Edwards PERIMOUNT Magna 
Mitral Ease Pericardial Bioprosthesis, Model 7300TFX, which will be designated as the Edwards 
Pericardial Mitral Bioprosthesis Model 11000M, do not raise any new questions of safety and 
effectiveness in subjects who require replacement of their native or prosthetic mitral valve. The 
only differences between the Model 7300TFX and the Model 11000M are modifications in tissue 
processing, valve sterilization, and packaging. Data collected in this clinical investigation was 
submitted to the FDA, and the Model 11000M valve is now approved to sell in the United States.  
In order to obtain sufficient long-term data on the valve, up to 25 Subjects at select hospitals that 
consent to extended follow-up will continue to be followed in this trial for up to 10 years (an 
additional 5 years from original study design). 
 
 

Sample Informed Consent 
Page 2 
 
Why am I asked to participate to this research trial? 
You are being asked to continue to participate in this trial as requested by the FDA so that 
Edwards may obtain long term safety and performance data on the valve that you received. This 
new mitral valve was developed to treat subjects having mitral valve disease like you. 
Trial design  
Up to 700  aortic valve replacement subjects and up to 175 mitral valve replacement subjects in 
up to 40 hospitals located throughout the United States, Canada, Europe and Asia Pacific will be 
enrolled in this trial. Your participation in this trial will not change your planned surgical 
treatment as all enrolled subjects will receive the Model 11000M valve, unless contraindicated 
by the trial doctor. The entire length of the trial is expected to last up to 10.5 years. Your 
participation will last for 10 years.  You will be asked to return to the hospital where the surgery 
was done and be checked by the trial doctor or his/her colleagues. You will be assessed at 
discharge, 1 month, 3 months, 12 months, and annually thereafter for 10 years from the time of 
implant of the Model 11000M valve into your heart. Please note the 1 month visit will be 
conducted by phone. 
 
Description of the Edwards Pericardial Mitral Bioprosthesis, Model 11000M  
The Edwards Pericardial Mitral Bioprosthesis, Model 11000M is an FDA-approved device. The 
Model 11000M valve is an FDA-approved Carpentier-Edwards PERIMOUNT Magna Mitral Ease 
7300TFX valve, with modifications in tissue processing, valve sterilization, and packaging.   
The Magna Mitral Ease valve consists of three tissue leaflets made of bovine (cow) pericardium 
(heart tissue). These leaflets have been treated with a new Edwards tissue process, built on the 
FDA-approved Edwards ThermaFix process to stabilize and preserve tissue. This process also 
allows the Model 11000M to be stored in non-liquid packaging and to not require rinsing prior to 
implant.  
How was the valve under investigation tested? 
The valve was tested on animals and in bench-top laboratory testing, in conformity with the U.S. 
Regulations. The results of these tests to date have shown that the valve is suitable for implant 
in humans. 
The technique used for implanting the valve is the same as your doctor uses with other biological 
heart valves. Each of the trial doctors involved in this clinical trial is properly trained on how to 
implant the Model 11000M valve. 
The Model 11000M valve is being tested in ongoing clinical trials. 
 
What will happen to me if I take part? 

Sample Informed Consent 
Page 3 
If you agree to participate in this trial, you will be treated like any other subject having a similar 
operation and you also will have some more tests (described below) to collect more information 
about the valve and the surgery. 
The decision about participating in this trial is entirely yours.  Please make sure that all your 
questions are addressed before you make a decision.  If you consent to participate, we will ask 
you to sign and date this informed consent form.  A copy of this form will be given to you.  
The trial doctor will then ask you questions and will run tests and procedures to see if you qualify 
for trial participation. These tests and procedures include: 
• Your blood pressure, heart rate, height, and weight will be measured (physical exam) 
• Your medical history and your current medications will be reviewed  
• Your blood will be collected for laboratory testing.  The blood draw will consist of a needle 
being stuck into a vein in your arm (or other area where a vein can be accessed).  
Approximately two tablespoons (30 mL) of blood will be drawn at this visit for routine 
tests including a complete blood count, plasma free hemoglobin or haptoglobin or serum 
LDH coagulation profile, and serum creatinine to test for kidney function.  Any remaining 
blood sample will be discarded according to hospital regulations. 
• An electrocardiogram (a test using a machine that records the electrical activity of your 
heart. The recording is done by putting self-adhesive discs on your chest) 
• An echocardiogram (a test using a machine that creates sound waves creating pictures of 
inside your heart. A small probe is put on the outside of your chest) 
• The severity of your health will be graded using a standard scale by the New York Heart 
Association (NYHA) based on your ability to do physical activities 
• You will complete a questionnaire to assess your quality of life 
• If you are a woman of child-bearing age (and are not sterile) a small amount of blood or 
urine will be obtained to check for pregnancy 
If the results of the tests and examinations do not meet the trial requirements and your doctor 
assesses that you are not qualified to participate in the trial, you will be excluded from the trial 
and the trial doctor will discuss with you an alternative treatment for your disease.  No further 
commitments related to this trial will be requested from you. 
If, as a result of the above mentioned tests and examinations, your doctor assesses that you are 
qualified to participate in the trial, you will be scheduled for surgery. Upon your approval, your 
personal physician will be informed of your participation in the clinical trial. 
Similar to other mitral valve replacement operations, this surgical procedure is performed under 
general anesthesia.  The beating of the heart is stopped and the blood circulation will continue 
using a “heart-lung” machine.   
If during surgery your trial doctor finds a reason not to implant the Model 11000M valve, you will 
receive an FDA-approved mitral valve. You will not have any further commitments related to this 
trial. 
If your trial doctor determines that there are no contraindications, you will receive the Model 
11000M valve and you will be considered enrolled in the trial.  

Sample Informed Consent 
Page 4 
During your surgery after the Model 11000M valve is implanted, a small tube used as a probe for 
a transesophageal echocardiogram (TEE) will be entered through your mouth and advanced 
down to the area of the heart.  The doctor will use this echocardiogram to take pictures of your 
heart.  This is part of every surgery to replace a heart valve.  
If the Model 11000M valve is replaced with another FDA-approved mitral valve at any time after 
enrollment, you will be followed for 30 days or until any symptoms or side effects that you may 
experience have resolved. Your investigational valve may be removed or explanted and sent to 
the Sponsor or an independent lab for further analysis. 
After your surgery and before you go home, you will have some more tests and examinations as 
described below: 
• Your blood pressure, heart rate and weight will be measured (physical exam) 
• Your current medications will be recorded  
• Blood tests (including a complete blood count, plasma free hemoglobin or haptoglobin or 
serum LDH and coagulation profile) 
• An electrocardiogram (once right after your procedure, and once before you go home) 
• An echocardiogram will be obtained to see that the newly implanted Model 11000M valve 
sits well in its position and that it works well 
• You will be asked if you have experienced any unusual symptoms or side effects since the 
procedure – any finding will be recorded in order to control your health status 
 
At 1 month after your surgery, you will be called and asked to provide information about your 
health status: 
• Your current medications will be recorded 
• Your health condition will be graded based on your ability to perform physical activities 
(NYHA class) 
• You will be asked if you have experienced any unusual symptoms or side effects since 
your last assessment 
• An appointment will be scheduled for you to return to the trial center approximately at 3 
months from your procedure date 
 
During your 3 month and subsequent annual follow-up visits, you will be asked to provide 
information about your health status and you will undergo the following procedures: 
• Your blood pressure, heart rate and weight will be measured (physical exam) 
• Your current medications will be recorded 
• Blood tests (including a complete blood count, plasma free hemoglobin or haptoglobin or 
serum LDH, and coagulation profile)  
• An electrocardiogram  
• An echocardiogram  
• Your health condition will be graded based on your ability to perform physical activities 
(NYHA class) 
• You will complete a questionnaire that will help your doctor to assess your quality of life 
(only at 12 month follow-up) 
• You will be asked if you have experienced any unusual symptoms or side effects since 
your last assessment 

Sample Informed Consent 
Page 5 
 
Participant responsibilities 
If you decide to participate in this research trial, you will have to follow the instructions given by 
your trial doctor and his colleagues and return to the hospital for all the follow-up visits until the 
tenth follow up year. Completing all trial visits is important to make sure that the trial results are 
complete and accurate. If you wish to stop participating in the trial or if you find you have not 
followed instructions listed above, it is important that you notify the trial doctor or research staff. 
Your participation in this research trial is entirely voluntary and it is your right to refuse to 
participate or withdraw at any time without penalty or loss of benefits to which you are otherwise 
entitled.  You are free to withdraw from the trial at any time without giving any reason, even if 
you have confirmed in writing that you want to take part.  Your decision to withdraw will not 
have any adverse effect whatsoever on your further treatment in our hospital. 
Giving false, incomplete, or misleading information about your medical history, including past 
and present use of medications, could have a very serious effect on your health.  It is very 
important that you give a true and complete medical history. 
What are the possible benefits of taking part? 
There are no guaranteed benefits from participation in this clinical investigation.   
 
Potential benefits resulting from this clinical trial include:  
• improvement of mitral valve function 
• acute relief of symptoms related to mitral stenosis 
• improvement in morbidity and mortality compared to similar/conventional devices  
 
In addition, information gained from the conduct of this trial may be of benefit to other people 
with the same medical condition in the future. The long-term results of using the investigational 
valve are not known at the present time.  
 
Alternative treatments include palliative medical therapy, mitral balloon valvuloplasty (opening 
the narrowed mitral valve with a balloon catheter) and surgical replacement of the mitral valve 
with another brand of prosthesis. 
What are the possible risks/inconveniences of taking part? 
You must understand that the treatment of choice for your condition is a heart valve replacement 
and that alternative valves are available.  
As with all prosthetic heart valves, there is a possibility that serious complications, sometimes 
leading to death, could develop that were not anticipated. In addition, complications and 
inconveniences due to individual subject reaction to an implanted device, or to physical or 
chemical changes in the components, particularly those of biological origin may occur, 
necessitating reoperation and replacement of the prosthetic device. These risks will be explained 
to you by your trial doctor. Unforeseeable risks may also occur.  Should any side effects occur, 
they will be fully assessed and you will be monitored closely.  

Sample Informed Consent 
Page 6 
You may experience events and/or outcomes that may include, but are not necessarily limited 
to, the following: 
 
Known/potential risks associated with the use of stented bioprosthetic heart valves include but 
are not limited to:  
 
 
Angina (chest pain or other pain 
from the heart) 
 
Bleeding diatheses/coagulopathy 
related to anticoagulant therapy 
(increased susceptibility to bleeding) 
 
Cardiac arrhythmias (change in or 
blockage of the heartbeat rhythm) 
 
Cardiac failure 
 Coronary ostial blockage (blockage 
of opening of coronary artery) 
 Endocarditis (infection of the valve) 
 
Hemolysis/Hemolytic anemia 
(breaking open of red blood cells 
with release of hemoglobin) 
 
Hemorrhage (bleeding) 
 
Immunological response 
 
Leaflet entrapment (impingement) 
 
Myocardial infarction (heart attack) 
 
Nonstructural valve dysfunction 
 
Malfunctions 
of 
valve 
due 
to 
distortion at implant, fracture of 
wireform, physical and or chemical 
deterioration of valve components 
 
Paravalvular/Perivalvular leak (blood 
leaking around the valve when it is 
closed) 
 
Patient prosthetic mismatch (PPM) 
(inappropriate sizing) 
 
Regurgitation/insufficiency (blood 
leaking through the valve when it is 
closed) 
 
Stenosis (narrowing of the valve) 
 
Thromboembolism/stroke 
(blood clot breaking off from the 
valve and causing blockage in the 
circulation downstream) 
 
Tissue 
deterioration 
including 
infection, calcification, thickening, 
perforation, degeneration, suture 
abrasion, instrument trauma, and or 
leaflet detachment 
 
Transient ischemic attack (TIA) 
(mini-stroke) 
 
Valve pannus  (excessive tissues 
growth around the valve) 
 
Valve thrombosis (blood clot 
attachment to the valve) 
 
 
Potential risks associated with mitral valve replacement surgery include but are not limited 
to: 
 
 
Allergic reaction  
 
Annular dissection (tear in the tissue 
around valve opening) 
 
Aortic/arterial dissection (tear in the 
artery) 
 
Bleeding, anticoagulant related 
(related to blood thinners) 
 
Bleeding, procedural/post-
procedural (during or after surgery) 
 
Cardiac arrest (heart stops beating) 

Sample Informed Consent 
Page 7 
 
Cardiogenic shock (not enough 
blood being pumped by the heart) 
 
Disseminated intravascular 
coagulation (DIC) (the blood clots 
too much) 
 
Esophageal rupture (tear or hole in 
the tube that connects the mouth to 
the stomach) 
 
Heart failure 
 
Hematoma (localized collection of 
blood) 
 
Heparin induced thrombocytopenia 
(HITs) (low platelet count in blood 
due to medication) 
 
Hypertension/Hypotension (blood 
pressure that is too low or too high) 
 
Hypoxemia (lack of oxygen) 
 
Infection, local or wound 
 
Infection, systemic (body-wide, 
called septicemia) 
 
Myocardial Infarction (heart attack) 
 
Multi-system organ failure (MOF) 
(example liver and or kidneys stop 
working) 
 
Pericardial effusion (fluid around the 
heart) 
 
Pericardial tamponade (a large 
amount of fluid around the heart 
such that is interferes with its 
normal performance) 
 
Pleural effusion (fluid around the 
lungs) 
 
Pulmonary edema (fluid in the lungs) 
 
Pneumonia (infection of the lungs) 
 
Renal dysfunction (kidney function 
worsening) 
 
Respiratory failure (lung failure 
where the level of oxygen in the 
blood becomes dangerously low) 
 
Thromboembolism (blood clot) 
– Venous, peripheral or central 
(blood clot in vein) 
– Arterial, peripheral or central 
(blood clot in artery) 
– Pulmonary, thrombus (blood clot 
in lung)
 
These complications may manifest clinically as symptoms including but not limited to abnormal 
heart murmur, exercise intolerance, shortness of breath, anemia, and/or fever. 
It is possible that these complications could lead to:  
• 
Reoperation 
• 
Explant (removal of the valve) 
• 
Permanent disability 
• 
Death 
 
Risks associated with the Model 11000M are anticipated to be the same as listed above for other 
mitral bioprosthetic valves and valve replacement surgery. 
You may require anti-coagulant therapy (a substance that prevents clotting of the blood) as a 
result of having your mitral valve replaced with the Model 11000M valve.  You may require long-
term anti-platelet therapy (aspirin, unless there is a reason you should not take it) even if long-
term anti-coagulant therapy is not required. 
Post procedural anti-coagulant and anti-platelet medications include the risk of causing severe 
bleeding and heavy blood loss. Because of this risk, anyone taking these drugs must take care to 
avoid injuries. Any falls, blows to the body or head, or other injuries should be reported to a 

Sample Informed Consent 
Page 8 
physician, as internal bleeding may occur without any obvious symptoms.  Post procedural anti-
coagulation and associated risks are no different with the investigational valve than with valves 
already approved by the FDA. 
Risks from taking a blood sample 
You will have routine blood samples taken from a vein in your arm by a needle stick.  Risks 
associated with drawing blood from your arm include slight discomfort and/or bruising.  
Infection, bleeding, clotting, or fainting also are possible, although unlikely.  The number of times 
that you will have a blood sample drawn for this trial is maximal 8 times over approximately 5 
years.  At maximum, two tablespoons (30 mL) of blood will be taken at a single visit.   
Risks from an electrocardiogram 
In rare circumstances, a rash or irritation at the location of the electrocardiogram electrode 
placement can occur due to the adhesive.  If this should occur, it will be assessed and treated 
using clinical standards of care with appropriate medication(s) and/or compresses. 
Risks from an echocardiogram 
A lubricant (gel) is used on the skin to improve picture quality and this may feel cold.  There are 
no known risks associated with receiving a transthoracic echocardiogram. 
Risks from an transesophageal echocardiography (TEE) 
The few risks of TEE involve passing the probe from your mouth down into your throat and 
esophagus. You may have a sore throat for a day or two. In very rare cases, TEE causes the 
esophagus to bleed. 
If I decide against participating in the clinical trial what other options do I have? 
If you decide not to participate in this trial, you can discuss with your doctor which options of 
heart valve replacement best suit your requirements.  There are a number of brands of 
bioprosthetic valves available.  Alternatives available to you may include continuation of your 
current heart medications and treatments without having surgery to replace your mitral valve.  It 
is important that you discuss these other options with your doctor. This does not in any way 
affect your further clinical care.  
What if something goes wrong? 
Your doctor and Edwards Lifesciences LLC will take all appropriate efforts to prevent any injury 
or illness which may occur as a result of your participation in this trial.  If you suffer any injury or 
illness as a direct result of participating in this trial, you will receive medical care and treatment 
at this hospital. Call your trial doctor immediately. Signing this consent does not affect any legal 
rights you have.  
Will my taking part in this trial be kept confidential? 
The records of this trial will be kept confidential. This section explains how your medical records 
might be used and disclosed if you agree to participate in this trial. 
All physicians involved in the trial follow a strict clinical protocol. You have the right to determine 
who has access to your health records.  Records collected in this trial includes your medical 

Sample Informed Consent 
Page 9 
history, the results of physical exams, lab tests and other diagnostic procedures as described 
above in this consent form, as well as basic demographic information and data related to your 
trial treatment. 
By signing this form: 
• You allow the research staff and/or the trial doctor to use your medical records for the 
trial and to disclose your health information to the Sponsor, Edwards Lifesciences LLC, or 
to the sponsor’s representatives, in order to review the results of the trial and to monitor 
the safety of participants. 
• You allow the trial doctor and/or sponsor to publish the results of the trial or discuss the 
results at conferences. If this is done, no information will be included that would reveal 
your identity. 
The information sent by the trial doctor and/or research staff to the Sponsor will not include your 
name, address, or other identifiers.  Instead, the trial doctor will assign a coded number to the 
records that are provided to the Sponsor.  However, your entire medical record may be reviewed 
at the trial doctor’s office and/or hospital by the Sponsor and/or Sponsor representatives, by 
regulatory/government agencies including the Food and Drug Administration (FDA) and the 
independent Institutional Review Board (IRB - a committee formally selected to approve, review 
and monitor research involving human subjects), and/or other regulatory agencies in other 
countries. The purpose of these reviews is to assure the safety and well-being of trial participants 
and the quality of the clinical trial. 
The trial doctor and/or research staff will make every effort to protect the privacy of your 
information.  However, absolute confidentiality cannot be guaranteed because of the need to 
disclose information as described above.   
This authorization does not have an expiration date.  If you do not cancel this authorization then 
it will remain in effect indefinitely. 
You can cancel this authorization at any time by giving a written notice to the trial doctor.  If you 
cancel this authorization, then you no longer will be able to participate in the trial, and the 
information that was collected prior to canceling the authorization may still be used and disclosed 
to the above-mentioned parties.  You will receive a signed copy of this consent for your records. 
All data collected within the scope of the trial may be forwarded to other persons or institutions 
not authorized for direct data inspection in an anonymized form only. 
Participation and Withdrawal 
You have the right to choose not to be in this trial or to stop being a part of this trial at any time 
without any consequences. This means that there will be no penalty or loss of medical benefits 
to which you are entitled. 
If you choose to stop being a part of this trial, you must first notify the trial doctor immediately 
so that a plan can be provided for your continued medical care.  At the time you stop taking part 
in the trial, you will be asked to return for a final safety evaluation that will include gathering 
information about your current medical condition and conducting any required procedures. For 
your own safety, you should go through the trial exit procedures any time you leave the trial and 
make arrangements for your continued medical care. 

Sample Informed Consent 
Page 10 
It is possible that your participation in this trial may be stopped at any time without asking you.  
This might happen if you do not follow the instructions given by the trial doctor or if the trial 
doctor believes it is in your best interest.  The trial also may be stopped for administrative, 
medical, or other reasons as determined by the trial doctor, the Sponsor, or regulatory 
authorities.  Any significant new findings developed during the course of this research that might 
affect your willingness to participate in the trial will be provided to you and the trial doctor. 
While participating in this trial, you should not take part in any other clinical trial.  This is to 
protect you from possible injury that may arise. 
Who is organizing and funding the research? 
This trial/research is organized by Edwards Lifesciences LLC, the Sponsor and the company that 
makes the Model 11000M valve. The clinical research staff will not be paid to include you in this 
trial but the hospital will be reimbursed for the costs incurred in conducting this research. 
Costs and Compensation 
You will be billed for all charges normally associated with heart valve replacement (including trial-
related visits) – only those required procedures outside of the routine standard of care will be 
paid for by the sponsor. There will be no financial compensation for your participation in this 
clinical trial.   
You will be reimbursed for the travel expenses you have in order to return to the hospital for the 
follow-up visits required during the trial. You will still be responsible for the cost of your usual 
ongoing medical care, including procedures and/or non-trial drugs that are not required by this 
clinical research trial.  If you have any questions, please ask the trial doctor, or a member of the 
research staff. 
You understand that all forms of medical diagnosis and treatment, whether routine or trial-
related, involve some risk of injury. In spite of all precautions, you might develop medical 
complications from participating in this research trial. You understand that the Sponsor or the 
hospital cannot assume liability for injury caused by the use of this particular valve or any other 
valve. In the event physical injury occurs as a result of participating in this research trial, the 
necessary facilities, emergency treatment and professional medical services will be available to 
you, just as they are to anyone. In the event of an unexpected injury directly related to the 
investigational device or the procedures described in the Clinical Research Protocol, the 
Sponsor will reimburse the hospital for the cost of treatment for any such injury, under the 
following conditions: 
• The costs of treatment are not paid for by your medical or hospital insurance or 
coverage; and 
• The injury is not due to negligence of the Investigator or the hospital; 
• The Investigator and the hospital have followed the Clinical Protocol 
requirements; and  
• You have followed the instructions of the Investigator  
You further understand that you do not waive any liability rights for personal injury by signing 
this form. 
Contact details for further information 

Sample Informed Consent 
Page 11 
If you require any further information before or during the trial, or if you have any questions after 
you have read this Subject Information Sheet/ Informed Consent, please contact the trial doctor 
responsible for you: 
Trial Doctor: ____________________________ 
 
Phone: ______________ 
Further information 
You consent to participate in a research trial and your data will be used in the statistical analysis 
of that clinical trial. It is understood that your personal identifiable data continues to be subject 
to data protection and shall not be disclosed to any third parties. Participation in this clinical 
trial is voluntary, and you can discontinue participation at any time without giving reasons, and 
without penalty. The Principal Investigator or the Sponsor also may decide on your premature 
discontinuation in this trial. 
Signature of subject or his/her legal representative 
I have received written information about the clinical trial or the information was read out to me 
and I had sufficient time to read this through and think about it.  I also was orally informed in 
detail by _____________________________ (name of clinical investigator) about the nature, 
significance and scope of the clinical trial; in particular about the objectives, conduct, benefit, 
risk, and insurance coverage including the associated obligations. All my questions were 
answered in an understandable way.  I do not have any further questions right now. I know that 
I can ask questions at any time, including during and after the clinical trial. 
• I declare my voluntary consent to the clinical trial. I am aware that I can refuse to participate 
or withdraw my consent at any time without incurring any penalties or disadvantages. 
• I agree that my medical data may be recorded in the context of this clinical trial.  I agree that 
the medical data may be forwarded in anonymous form to authorized specialists for data 
processing and scientific evaluation and to the competent authorities for review. 
• At the same time, I agree that my health data may be recorded in the context of this clinical 
trial and representatives of the Sponsor or the regulatory agencies may inspect my data for 
review purposes. 
• Finally, I agree to scientific publication of the research results in compliance with provisions 
of data protection legislation. 
 
_____ I agree / _____ I do not agree that my primary care physician may be informed about my 
participation in this trial. 
 
 

Sample Informed Consent 
Page 12 
Print name of trial participant 
 
 
Date 
 
Time1 
Signature of trial participant 
 
 
 
 
 
 
 
 
 
 
Print name of legal representative (if 
required) 
 
Date 
 
Time 
 
 
 
 
 
 
Signature of legal representative 
(if required) 
 
 
 
 
Signature of Person Obtaining Consent 
I have explained the clinical trial to the subject or his/her legal representative and answered all 
his/her questions. I have the impression that he/she understands the information contained in 
this document and gives his/her consent to participate on his/her own free will. The subject was 
given a copy of the signed consent form. 
 
Name of Person Obtaining Consent 
(printed) 
 
Date 
 
Time 
 
 
 
Signature of Person Obtaining 
Consent 
 
Clinic 
 
 
1 Required only if consent is taken on the same day as the trial procedure 

EDWARDS LIFESCIENCES LLC 
CLINICAL INVESTIGATIONAL PLAN 
PROTOCOL NUMBER: 2012-02 
 
ATTACHMENTS 
 
CONFIDENTIAL AND PROPRIETATARY DATA: This document and the information contained herein may not be reproduced, used, or disclosed 
without written permission from Edwards Lifesciences LLC 
REVISION J: 03 MARCH 2021 
 
 
 
 
ATTACHMENT D – CASE REPORT FORMS 

 
EDWARDS 
          TRIAL NUMBER 2012-02 
COMMENCETM TRIAL  - REV H 
STUDY SCREENING 
PAGE 1 OF 2 
 
 
Subject Study ID  
201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
Inclusion Criteria 
 
 
 
DATE OF 
SCREENING 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
D 
D 
 
M 
M 
M 
 
Y 
Y 
Y 
Y 
YES 
NO 
NAP 
 
 
 
 
1. 
SUBJECT IS 18 YEARS OR OLDER 
 
 
 
2. 
SUBJECT HAS PROVIDED WRITTEN INFORMED CONSENT PRIOR TO TRIAL PROCEDURES  
 
IF YES, DATE OF CONSENT:_________________________    TIME:________________________________ 
 
 
 
3. 
SUBJECT AGREES TO ATTEND ALL FOLLOW-UP ASSESSMENTS FOR UP TO 5 YEARS AND IS WILLING TO COMPLY WITH 
SPECIFIED FOLLOW-UP EVALUATIONS AT CLINICAL INVESTIGATIONAL SITES THAT ARE PARTICIPATING IN THE 
COMMENCE TRIAL AND/OR OBTAIN THE PROTOCOL-SPECIFIED DIAGNOSTIC TESTS AT CENTERS THAT ARE UNDER THE 
SAME IRB OR THE SAME HEALTHCARE SYSTEM 
 
 
 
4. 
SUBJECT IS DIAGNOSED WITH AORTIC OR MITRAL VALVE DISEASE REQUIRING VALVE REPLACEMENT BASED ON PRE-
OPERATIVE EVALUATION  
 
 
 
5. 
SUBJECT IS SCHEDULED TO UNDERGO PLANNED AORTIC OR MITRAL VALVE REPLACEMENT WITH OR WITHOUT 
CONCOMITANT BYPASS SURGERY 
 
 
 
6. 
SUBJECT IS SCHEDULED TO UNDERGO PLANNED AORTIC VALVE REPLACEMENT WITH OR WITHOUT RESECTION AND 
REPLACEMENT OF THE ASCENDING AORTA FROM THE SINOTUBULAR JUNCTION AND WITHOUT THE NEED FOR 
CIRCULATORY ARREST FOR HEMI ARCH OR ARCH REPLACEMENT 
 
 
IF ANY RESPONSE BELOW IS “YES” THE SUBJECT IS NOT ELIGIBLE FOR THE STUDY 
 
EXCLUSION CRITERIA 
 
YES 
NO 
 
 
 
1. 
SUBJECT REQUIRES EMERGENCY SURGERY 
 
 
2. 
SUBJECT REQUIRES PLANNED MULTIPLE VALVE REPLACEMENT/REPAIR (WITH THE EXCEPTION OF MITRAL VALVE 
REPLACEMENT WITH TRICUSPID VALVE REPAIR) 
 
 
3. 
SUBJECT HAS PRIOR VALVE SURGERY, WHICH INCLUDED IMPLANT OF A BIOPROSTHETIC VALVE, MECHANICAL VALVE, OR 
ANNULOPLASTY RING THAT WILL REMAIN IN SITU 
 
 
4. 
SUBJECT REQUIRES A SURGICAL PROCEDURE OUTSIDE OF THE CARDIAC AREA (E.G. VASCULAR BYPASS) 
 
 
5. 
SUBJECT REQUIRES SURGICAL REPLACEMENT OF THE AORTIC ROOT 
 
 
6. 
SUBJECT HAS ACTIVE ENDOCARDITIS/MYOCARDITIS OR ENDOCARDITIS/MYOCARDITIS WITHIN 3 MONTHS PRIOR TO THE 
SCHEDULED AVR SURGERY 
 
 
 
7. 
SUBJECT HAS RENAL INSUFFICIENCY AS DETERMINED BY CREATININE (S-CR) ≥ 2.5 MG/DL OR END-STAGE RENAL DISEASE 
REQUIRING CHRONIC DIALYSIS AT SCREENING VISIT  
 
 
 
8. 
SUBJECT HAS AN MRI OR CT-SCAN CONFIRMED STROKE, CEREBROVASCULAR ACCIDENT (CVA), OR TRANSIENT ISCHEMIC 
ATTACK (TIA) WITHIN 6 MONTHS (180 DAYS) OF THE VALVE SURGERY 
 
 
9. 
SUBJECT HAS ACUTE MYOCARDIAL INFARCTION (MI) WITHIN 30 DAYS PRIOR TO THE SCHEDULED AORTIC OR MITRAL VALVE 
REPLACEMENT SURGERY 
 
 
10. 
SUBJECT HAS PRESENCE OF NON-CARDIAC DISEASE LIMITING LIFE EXPECTANCY TO LESS THAN 12 MONTHS 
 
 
11. 
SUBJECT IS DIAGNOSED WITH HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY (HOCM)  
 
 
12. 
SUBJECT IS DIAGNOSED WITH ABNORMAL CALCIUM METABOLISM AND HYPERPARATHYROIDISM 
 
 
13. 
SUBJECT EXHIBITS A LEFT VENTRICULAR EJECTION FRACTION ≤ 20% AS VALIDATED BY DIAGNOSTIC PROCEDURE PRIOR TO 
PLANNED VALVE SURGERY 

 
 
ASSESSMENT 
PAGE 1 OF 3 
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
VISIT DATE: ___ ___ / ___  ___  ___  /  ___  ___  ___  ___  
                                D     D      M     M     M         Y      Y      Y      Y  
1. Primary method of contact with subject: 
 
 
    HOSPITAL/ CLINIC VISIT 
 
 
    PHONE INTERVIEW 
        
 
    IN-PATIENT ADMISSION 
 
 
 
PHYSICAL ASSESSMENT / VITAL SIGNS: 
          WEIGHT:                                         ______  
   kg             
   lbs 
            HEART RATE:                                 ______ bpm 
            SYSTOLIC BLOOD PRESSURE     ______mmHg 
            DIASTOLIC BLOOD PRESSURE    ______mmHg 
CURRENT NYHA CLASSIFICATION 
 
 
 
CLASS I  
 
 
 
 
 
NOT DONE 
 
 
CLASS II 
 
 
 
 
 
NOT APPLICABLE AT DISCHARGE 
 
 
CLASS III 
 
 
CLASS IV 
CANADIAN CARDIOVASCULAR SOCIETY (CCS) ANGINA CLASS 
 
 CLASS 0 
 
 CLASS I 
 CLASS II 
 
 CLASS III 
 CLASS IV  
            
 UNKNOWN                    
NOT APPLICABLE AT DISCHARGE 
 
 
CURRENT MEDICATIONS  
YES    NO 
       
    MEDICATION LIST WAS COLLECTED 
 
ECHOCARDIOGRAPHY  
YES    NO 
       
    ECHOCARDIOGRAM WAS COMPLETED 
 
DATE OF EXAM:  _________________________ (DD/MMM/YYYY)  
 

 
 
ASSESSMENT 
PAGE 2 OF 3 
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
ELECTROCARDIOGRAM (ECG): 
YES    NO 
       
    ECG WAS COMPLETED 
 
DATE OF EXAM: ________________________________ (DD/MMM/YYYY) 
CARDIAC RHYTHM / CONDUCTION DISTURBANCES 
YES        NO 
   
   IMPLANTED WITH PERMANENT PACEMAKER (IF YES, SPECIFY TYPE) 
   CONTINUOUS  
 
 
   INTERMITTENT (Rate responsive/ On demand) 
 
 
   IMPLANTED WITH IMPLANTABLE CARDIOVERTER DEFIBRILLATOR (ICD/AICD)  
 
 
  SINUS RHYTHM  
 
 
   SINUS TACHYCARDIA 
 
 
   SINUS BRADYCARDIA 
 
 
   ATRIAL FIBRILLATION/ SUPRAVENTRICULAR TACHYCARDIA (INDICATE EPISODAL PATTERN) 
   PAROXYSMAL (SELF-TERMINATING) 
 
 
   PERSISTENT (NON-SELF TERMINATING) 
 
   ATRIAL FLUTTER 
 
 
   TACHYCARDIA-BRADYCARDIA SYNDROME 
 
 
   VENTRICULAR TACHYCARDIA (IF YES, INDICATE EPISODAL PATTERN) 
   NONSUSTAINED/PREMATURE VENTRICULAR COMPLEXES (PVC) 
 
 
   SUSTAINED 
 
 
   OTHER CARDIAC ARRHYTHMIA (IF YES, SPECIFY)_________________________________________________ 
  
    AV BLOCK (IF YES, INDICATE DEGREE) 
 
 
   1ST   
 
   UNKNOWN 
 
 
   2ND 
 
   3RD  
  
   BUNDLE BRANCH BLOCK/ INTRAVENTRICULAR CONDUCTION DELAY (IF YES, INDICATE BRANCH) 
 
 
   LEFT – COMPLETE  
 
 
   RIGHT - COMPLETE 
 
 
   LEFT- INCOMPLETE  
 
 
   RIGHT- INCOMPLETE 
  
   OTHER CONDUCTION DISTRUBANCE, SPECIFY: 
_____________________________________________________________________________________________ 

 
 
ASSESSMENT 
PAGE 3 OF 3 
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
BLOOD DATA 
YES    NO 
       
    BLOOD LABS WERE DRAWN AT THIS VISIT 
 
             
QUALITY OF LIFE SURVEY 
YES    NO 
       
    QOL SURVEY COMPLETED? 
 
DID ANY ADVERSE EVENTS OCCUR SINCE THE LAST FOLLOW-UP ASSESSMENT?  
   YES 
   NO 
IF YES, COMPLETE ADVERSE EVENT FORM 
Categories include: 
Blood and lymphatic (including ALL bleeding complications) 
Cardiovascular –Arrhythmia 
Cardiovascular - Regurgitation  
Cardiovascular - Stenosis  
Cardiovascular - Embolic Event/Valve Thrombosis  
Cardiovascular - Misc  
Device Dysfunction  
Gastrointestinal/Hepatic  
Genitourinary/Renal  
Pulmonary/Respiratory  
Peripheral Vascular  
Psychiatric  
Muscular Skeletal/Dermatologic  
Nonspecific or Unknown Body System  
 
 
 
 
 
DATE SIGNED 
 
 
 
 
 
 
 
 
 
 
 
SIGNATURE 
 
D 
D 
 
M 
M 
M 
 
Y 
Y 
Y 
Y 
 

 
 
BASELINE DEMOGRAPHICS 
FORM
PAGE 1 OF 1
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
VISIT DATE: ___ ___ / ___  ___  ___  /  ___  ___  ___  ___  
                       D     D      M    M     M         Y     Y     Y      Y  
DATE OF BIRTH 
__ 
__ / __ 
__ 
__ / __ 
__ 
__ 
__ 
OR YEAR
__ 
__ 
__ 
__ 
AND 
AGE __ 
__ 
__ 
 
D 
D  M 
M 
M  Y 
Y 
Y 
Y 
 
 
Y 
Y 
Y 
Y 
 
Y 
Y 
Y 
GENDER     
 MALE  
 FEMALE 
 
 
PREGNANCY TEST (IF FEMALE) 
 
 NOT PERFORMED 
  
POST-MENOPAUSAL / SURGICALLY STERILE 
 
OTHER ____________________________________________________________________ 
 
 PERFORMED 
 
 
 
 
 
 POSITIVE 
 NEGATIVE 
 
 
 
DATE TEST PERFORMED__________________ (DD/MMM/YYYY) 
RACE/ ETHNICITY 
  DECLINED TO IDENTIFY 
 
 
ETHNICITY 
  HISPANIC OR LATINO    
  NOT HISPANIC OR LATINO    
RACE 
     
  AMERICAN INDIAN OR ALASKA NATIVE  
    
     
   ASIAN 
 
 
 
     
   AFRICAN AMERICAN OR BLACK 
 
       
 
     
   NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER       
    
     
   WHITE    
       
 
      
SUBJECT HEIGHT:  __________________________
   cm 
   in 
 
 
CURRENT LEFT VENTRICULAR EJECTION FRACTION (LVEF)   ___________ % 
 
SERUM CREATININE LEVEL (mg/dL) ____________ 
 
IS THIS VALUE WITHIN THE NORMAL RANGE? 
 
NO 
 
 
WAS THIS RESULT CLINICALLY SIGNIFICANT? 
 
 
NO     
YES 
 
YES 
 
 
 
 
DATE
__ 
__ /
__ 
__ 
__ / __ 
__ 
__ 
__ 
 SIGNATURE 
D 
D 
M 
M 
M 
 
Y 
Y 
Y 
Y 
 

 
         
 
BLOOD DATA 
PAGE 1 OF 1 
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
Blood Draw Date:  ___ ___ / ___  ___  ___  /  ___  ___  ___  ___  
                                         D     D       M    M     M         Y     Y     Y      Y  
 
Blood Parameters  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
       Is this value within       Was the result clinically 
DONE 
NOT  
DONE 
 
 
 
       Values                                                 normal ranges?              significant?    
                                                                                                                       Yes         No             Yes         No 
 
  
 
 
 WHITE BLOOD CELLS (WBC):   __________  103/ 
µL
 
 
 
 
   
 
    
 
 
  
 
 
  RED BLOOD CELLS (RBC):      __________      
   106 /µL 
 
 
   
 
    
 
 
 
 
 
 
 
 
            
    1012 /L 
 
 
 
 
 
   
 
  
 
 
   HEMOGLOBIN :                      __________   
    g/dL 
 
 
   
 
    
 
 
 
 
 
 
 
 
    
    mmol/L   
                                                                     
    mg/dL     
 
 
 
 
 
   
 
  
 
 
   
 HEMATOCRIT:                              __________  % 
 
 
 
   
 
    
 
 
    
 
    PLATELET COUNT :                   __________  103/ µL 
    
 
 
 
 
  
 
   
 
 
 
 
  
 
 
 
 
 
 COAGULATION PROFILE: 
 
 
INR 
__________ 
 
 
PTT 
__________ 
     
                    PT 
__________ 
 
 
 
 
  
 
 
 
 
  PLASMA FREE HEMOGLOBIN :    __________       
    mg/dL 
 
 
   
 
    
 
 
 
 
 
 
 
 
                  
    mmol/L  
                                                                                   
    g/dL          
OR
 
 
   
    106 /uL           
 
 
 
 
  
 
 
 
 
  HAPTOGLOBIN :    __________       
    mg/dL 
 
 
   
 
    
 
 
 
 
OR 
 
 
 
 
  
 
 
 
 
SERUM LDH :    __________       
    IU/L 
 
 
   
 
    
 
       
 
DATE SIGNED 
SIGNATURE 
 
D D  M M M  Y Y Y Y 
 
 

 
 
      
 
MEDICATIONS 
PAGE 1 OF 1 
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
DATE INFORMATION COLLECTED:  _______________________________________ (DD/MMM/YYYY) 
 
CURRENT MEDICATIONS PLEASE INDICATE WHAT TYPE OF MEDICATIONS THE SUBJECT IS CURRENTLY TAKING: 
 
YES    NO     
 
 
 
ACE OR ARB INHIBITORS 
 
 
 
ANTIARRHYTHMICS 
 
 
 
                                 
    BETA BLOCKERS (PROPANOLOL, ESMOLOL) 
                            
    OTHER (SODIUM/ POTASSIUM CHANNEL BLOCKERS—AMIODARONE)   SPECIFY: 
 
                                   _____________________________________________________________ 
 
 
 
 
 
ANTICOAGULANTS 
 
 
 
                                  
    WARFARIN -- COUMADIN OR DERIVATIVES 
                        
    OTHER, SPECIFY: _____________________________________________________________ 
 
 
 
ANTIPLATELETS 
 
 
 
                                  
    DIPYRIDAMOLE -- PERSANTINE 
                        
    ASPIRIN – ECOTRIN OR ENTROPHEN 
                        
    TICLOPIDINE -- TICLID 
                        
    CLOPIDOGREL --PLAVIX 
 
 
 
 
    OTHER, SPECIFY: _____________________________________________________________ 
 
 
 
CALCIUM BLOCKER 
 
 
 
DIURETIC 
 
 
 
LIPID LOWERING 
 
 
 
NITRATES 
 
 
 
STEROIDS 
 
 
DATE 
 
 
  
 
 
  
 
 
 
SIGNATURE 
D 
D 
 
M 
M 
M 
 
Y 
Y 
Y 
Y 
 

 
 
           
 
MEDICAL HISTORY
PAGE 1 OF 8
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
 
CARDIOVASCULAR MEDICAL HISTORY 
 
YES 
NO 
 
 
 
CORONARY ARTERY DISEASE – (INDICATE WHICH NATIVE CORONARY VESSEL HAS ≥ 50% 
NARROWING) 
 
 
                        
    LEFT ANTERIOR DESCENDING (LAD) CORONARY ARTERY 
                        
    CIRCUMFLEX CORONARY ARTERY 
                        
    RIGHT CORONARY ARTERY 
                        
    LEFT MAIN CORONARY ARTERY 
 
 
CAROTID ARTERY DISEASE – (INDICATE THE SEVERITY OF DISEASE) 
 
 
                         
     CAROTID OCCLUSION (>79% DIAMETER OCCLUSION) 
                         
     ≥ 50% STENOSIS BUT NO OCCLUSION 
                         
     < 50% STENOSIS 
 
 
PERIPHERAL ARTERY /VASCULAR DISEASE  (INDICATE WHICH SYMPTOMS THE SUBJECT HAS EXPERIENCED)
 
 
 
 
  
     CLAUDICATION 
                         
     ˃ 50% STENOSIS BUT OF ANY PERIPHERAL ARTERY 
                         
    AORTIC ANEURYSM 
 
 
PULMONARY HYPERTENSION 
 
 
WHAT IS THE SEVERITY OF THE CONDITION? 
                        
    MILD (PULMONARY ARTERY SYSTOLIC PRESSURE <31mmHg) 
                        
    MODERATE (PULMONARY ARTERY SYSTOLIC PRESSURE 31-55mmHg) 
                            
 SEVERE (PULMONARY ARTERY SYSTOLIC PRESSURE IS >55mHg) 
 
 
 
SYSTEMIC HYPERTENSION     
 
 
    HAS A DOCUMENTED HISTORY OF HYPERTENSION DIAGNOSED AND TREATED WITH MEDICATION, DIET,    
         AND/OR EXERCISE 
 
          
    HAS PRIOR DOCUMENTATION OF BLOOD PRESSURE >140 MMHG SYSTOLIC OR 90 MMHG DIASTOLIC FOR PATIENTS WITHOUT    
                    DIABETES OR CHRONIC KIDNEY DISEASE; OR PRIOR DOCUMENTATION OF BLOOD PRESSURE >130 MMHG SYSTOLIC OR 80   
                    MMHG DIASTOLIC ON AT LEAST 2 OCCASIONS FOR PATIENTS WITH DIABETES OR CHRONIC KIDNEY DISEASE    
                 
         
  IS CURRENTLY ON PHARMACOLOGIC THERAPY TO CONTROL HYPERTENSION  
 
 
 
CARDIOMYOPATHY 
 
 
 
 
                        
    PRIMARY/INTRINSIC (HYPERTROPHIC, DILATED, ETC) 
                        
    SECONDARY/EXTRINSIC (ISCHEMIC, DIABETIC, ETC)                   
 
 
CONGESTIVE HEART FAILURE 
 
 
AORTIC STENOSIS 
                 IF YES: 
                        
     MILD 
                        
    MODERATE 
                            
    SEVERE  
                            
    UNKNOWN 
 
 
AORTIC INSUFFICIENCY 

 
 
           
 
MEDICAL HISTORY
PAGE 2 OF 8
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
 
 
                        
    +1TRACE 
                        
    +2 MILD 
                        
    +3 MODERATE 
                            
    +4 SEVERE 
 
 
MITRAL STENOSIS 
                       IF YES: 
                        
     MILD 
                        
    MODERATE 
                            
    SEVERE 
  
                             
    UNKNOWN 
 
 
MITRAL INSUFFICIENCY 
 
 
                        
    +1TRACE 
                        
    +2 MILD 
                        
    +3 MODERATE 
                            
    +4 SEVERE 
   
    
 
PULMONARY STENOSIS 
  IF YES: 
                        
     MILD 
                        
    MODERATE 
                            
    SEVERE 
  
                             
    UNKNOWN 
   
    
 
PULMONARY INSUFFICIENCY 
 
 
                        
    +1TRACE 
                        
    +2 MILD 
                        
    +3 MODERATE 
                        
    +4 SEVERE 
                            
     OTHER, SPECIFY: ________________________________________________________________
   
    
 
TRICUSPID STENOSIS 
  IF YES: 
                        
     MILD 
                        
    MODERATE 
                            
    SEVERE 
  
                             
    UNKNOWN 
   
    
 
TRICUSPID INSUFFICIENCY 
 
 
                        
    +1TRACE 
                        
    +2 MILD 
                        
    +3 MODERATE 
                        
    +4 SEVERE 
                            
     OTHER, SPECIFY:  
___________________________________ 
 
                    
 
                                              
 
 
MYCARDIAL INFARCTION       (IF YES, INDICATE TYPE AND DATE OF LAST OCCURRENCE) 
 
 
 
 
   STEMI           ___ ___ / ___  ___  ___  /  ___  ___  ___  ___  
                                                       D    D      M     M     M         Y     Y     Y       Y 
 
 
 
   NON STEMI   ___ ___ / ___  ___  ___  /  ___  ___  ___  ___  
                                                       D    D      M     M     M         Y     Y     Y       Y 
 
                                 
   OTHER         ___ ___ / ___  ___  ___  /  ___  ___  ___  ___  
                                                       D    D      M     M     M         Y     Y     Y       Y 
 
 

 
 
           
 
MEDICAL HISTORY
PAGE 3 OF 8
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
 
                                  
   UNK               ___ ___ / ___  ___  ___  /  ___  ___  ___  ___  
                                                       D    D      M     M     M         Y     Y     Y       Y 
 
                        IF DATE IS UNKNOWN, APPROXIMATELY HOW MANY MONTHS AGO DID THE LAST MI OCCUR? 
                        
                       _____________________________________MONTHS AGO 
 
 
                      IF UNKNOWN, DID THE EVENT OCCUR >5 YEARS AGO?     YES 
   NO 
       
 
   
    
 
CARDIAC RHYTHM ABNORMALITIES/ CONDUCTION DISTURBANCES 
 
 
HAS THE SUBJECT EVER HAD THE FOLLOWING CARDIAC RHYTHMS? 
 
 
                        
    SINUS TACHYCARDIA 
                        
    SINUS BRADYCARDIA 
                        
    TACHYCARDIA- BRADYCARDIA SYNDROME 
                        
    ATRIAL FIBRILLATION/SUPRAVENTRICULAR TACHYCARDIA 
                                                  
    PAROXYSMAL 
                                                  
    PERSISTENT 
                                                   IS THIS A PERMANENT CONDITION?   YES 
   NO 
      
 
                        
    ATRIAL FLUTTER 
                        
    TACHYCARDIA-BRADYCARDIA SYNDROME 
                        
    VENTRICULAR TACHYCARDIA 
                                                  
    NONSUSTAINED/PREMATURE VENTRICULAR COMPLEXES 
                                                  
    SUSTAINED 
                        
    OTHER CARDIAC ARRHYTHMIA 
                               PLEASE SPECIFY: ______________________________________________________ 
 
HAS THE SUBJECT EVER SHOWN SIGNS OF THE FOLLOWING CONDUCTION DISTURBANCES? 
                   
    AV BLOCK 
                               INDICATE THE LAST RECORDED DEGREE OF AV BLOCK 
                        
    1st 
                        
    2nd  
                        
    3rd  
                        
    UNKNOWN 
                  
    BUNDLE BRANCH BLOCK/ INTRAVENTRICULAR BLOCKS 
                               INDICATE BRANCH 
                       
    LEFT- COMPLETE         
    LEFT-INCOMPLETE 
                       
    RIGHT- COMPLETE       
    RIGHT - INCOMPLETE 
 
                
    LEFT ANTERIOR FASCULAR BLOCK                    
                      
    LEFT POSTERIOR FASICULAR BLOCK       
                      
    NONSPECIFIC INTRAVENTRICULAR CONDUCTION DEFECTS                  
                  
    OTHER CONDUCTION DISTURBANCE _________________________________________________ 
 
   
    
 
TRANSIENT ISCHEMIC ATTACK (TIA; RECOVERED WITHIN 24 HOURS) 
 
 
IS THE DATE WHEN THE LAST KNOWN TIA OCCURRED KNOWN? 
                     
                   DATE: ____________________________________ (DD/MMM/YYYY) 
 
                      IF DATE IS UNKNOWN, APPROXIMATELY HOW MANY MONTHS AGO DID THE LAST MI OCCUR? 

 
 
           
 
MEDICAL HISTORY
PAGE 4 OF 8
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
                        
                       _____________________________________MONTHS AGO 
 
 
                      IF UNKNOWN, DID THE EVENT OCCUR >5 YEARS AGO?     YES 
   NO 
 
 
 
 
CEREBROVASCULAR ACCIDENT (CVA/STROKE; DID NOT RECOVER WITHIN 24 HOURS) 
 
 (IF YES, INDICATE TYPE OF EVENTS AND DATE OF LAST OCCURRENCE) 
 
 
 
        
 
  
  DATE OF LAST KNOWN CVA 
 
 
                  
 
                                                                ___ ___ / ___  ___  ___  /  ___  ___  ___  ___  
                                                       D     D        M    M     M         Y     Y     Y      Y 
          
 
    
                      IF DATE IS UNKNOWN, APPROXIMATELY HOW MANY WEEKS AGO DID THE LAST TIA OCCUR? 
                        
                       _____________________________________WEEKS AGO 
 
 
                      IF UNKNOWN, DID THE EVENT OCCUR >5 YEARS AGO?     YES 
   NO 
       
         
 
     
                 DOES THE SUBJET HAVE SEVERE IMPAIRMENT OF MOBILITY AS A RESULT OF A NEUROLOGICAL   
                 DYSFUNCTION?                YES 
   NO 
       
   
 
 
ENDOCARDITIS 
 
 
                        
     CURENTLY BEING TREATED 
                        
     TREATED WITHIN THE LAST 3 MONTHS (NOT CURRENTLY BEING TREATED)  
                        
     TREATED > 3 MONTHS AGO 
 
 
 
 
 MYOCARDITIS 
 
 
                        
     CURENTLY BEING TREATED 
                        
     TREATED WITHIN THE LAST 3 MONTHS (NOT CURRENTLY BEING TREATED)  
                        
     TREATED > 3 MONTHS AGO   
 
 
HYPERLIPIDEMIA OR HYPERCHOLESTEROLEMIA 
   
     
 
RHEUMATIC FEVER 
 
PRIOR CARDIOVACULAR SURGICAL INTERVENTIONS 
 
HOW MANY CARDIOVASCULAR SURGERIES HAS THE SUBJECT PREVIOUSLY HAD? (Any vascular intervention including CABG, PTCA, Stent, 
PCI, Endarterectomy, endovascular angioplasties) 
                   
    0 
                        
    1 
                        
    2 
                        
    3 
                                  
    ≥ 4 
 
HOW MANY CARDIAC/HEART SURGERIES HAS THE SUBJECT PREVIOUSLY HAD? (Valve replacements/ repairs/ valvuloplasties/ 
commisurotomies/  ASD and PFO repairs, MAZE/ablation procedures) 
                   
    0 
                        
    1 
                        
    2 
                        
    3 
                                  
    ≥ 4 
 
HAS THE SUBJECT REQUIRED AMPUTATION OF A LIMB DUE TO ARTERIAL DISEASE?   YES 
   NO 
    
 

 
 
           
 
MEDICAL HISTORY
PAGE 5 OF 8
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
HAS THE SUBJECT BEEN IMPLANTED WITH A PERMANENT PACEMAKER OF AN IMPLANTABLE CARDIOVERTER DEFRIBRILLATOR?   
Yes 
No 
 
 
 
 
 
AICD / PACEMAKER IMPLANT 
 
 
 
SPECIFY THE TYPE OF IMPLANT THE SUBJECT HAS: 
                        
    INTERMITTANT (RATE-RESPONSIVE/ON DEMAND) PACEMAKER 
                        
   CONTINUOUS PACEMAKER 
                        
    ICD/AICD 
 
 
 
 
 
 
 
 
IF YES, INDICATE DATE OF IMPLANT  ___ ___ / ___  ___  ___  /  ___  ___  ___  ___  
                                                                          D    D      M     M     M         Y     Y     Y      Y 
 
 
 IF DATE IS UNKNOWN, APPROXIMATELY HOW MANY MONTHS AGO WAS THE SUBJECT 
IMPLANTED?                        
                       _____________________________________MONTHS AGO 
 
                      IF UNKNOWN, DID THE EVENT OCCUR >5 YEARS AGO?     YES 
   NO 
       
WERE SURGICAL INTERVENTIONS PERFORMED ON ANY OF THE FOLLOWING CARDIOVASCULAR COMPONENTS? 
 
 
 
CAROTID ARTERIES 
 
 
 
WHAT TYPES OF INTERVENTION WAS DONE ON THE CAROTIDS? 
 
 
 
                        
    ENDARTERECTOMY 
                        
    ENDOVASCULAR ANGIOPLASTY AND STENTING 
                            
    OTHER INTERVENTION ON THE CAROTIDS: ___________________________________________ 
 
 
 
ABDOMINAL AORTA  
 
 
 
THORACIC AORTA  
 
 
 
LIMB ARTERIES  
 
 
 
CORONARY ARTERIES 
 
                                  
                             WHAT TYPE OF INTERVENTIONS HAVE BEEN PERFORMED? 
                                  
                              CABG             YES 
   NO 
     
   
 
 
 
                        
    1 GRAFT 
    2 GRAFTS 
                        
    3 GRAFTS 
    4 GRAFTS 
                        
    UNKNOWN 
                               PTCA (BALLOON ANGIOPLASTY)/ PERCUTANEOUS CORONARY INTERVENTION (PTCI)      YES 
   NO 
       
 
 
         WAS A STENT EMPLOYED FOR ANY OF THE PAST PTCA/PTCI PROCEDURES?                     YES 
   NO 
 
 
 
 
 
        OTHER INTERVENTION ON THE CORONARY ARTERIES:  YES 
   NO 
       
 
        ______________________________________________ 
   
 
 
 
AORTIC VALVE 
 
 
 
                        
    VALVULOPLASTY 
                        
    VALVE REPLACEMENT                         
                        
    OTHER REPAIR:_________________________________________________  

 
 
           
 
MEDICAL HISTORY
PAGE 6 OF 8
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
 
 
 
MITRAL VALVE 
 
 
 
                        
    ANNULOPLASTY 
                        
    VALVULOPLASTY 
                        
    VALVE REPLACEMENT 
                        
    OTHER REPAIR:____________________________________________________ 
 
 
 
PULMONARY VALVE 
 
 
 
                        
    VALVULOPLASTY 
                        
    VALVE REPLACEMENT                         
                        
    OTHER REPAIR:_________________________________________________ 
                                             
 
 
 
TRICUSPID VALVE 
 
 
 
                        
    ANNULOPLASTY 
                        
    VALVULOPLASTY 
                        
    VALVE REPLACEMENT 
                        
    OTHER REPAIR:____________________________________________________ 
  
 
 
 
OTHER CARDIOVASCULAR COMPONENT, SPECIFY (LOCATION  AND TYPE OF PROCEDURE PERFORMED):  
 
_____________________________________________________________________________________ 
 
 

 
 
           
 
MEDICAL HISTORY
PAGE 7 OF 8
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
NON-CARDIOVASCULAR RISK FACTORS 
 
DOES THE SUBJECT CURRENTLY HAVE OR HAS THE SUBJECT EVER HAD THE FOLLOWING DISEASES?
 YES   NO    
  
 
 
BLEEDING DIATHESIS  
 
 
 ACUTE ANEMIA (HEMOGLOBIN <10.0G/DL OR 6.2 MMOL/L) 
 BLEEDING DIATHESIS 
 COAGULOPATHIES 
 LEUKOPENIA (WBC <3.5 x 10^3/ uL) 
 THROMBOCYTOPENIA (PLATELET COUNT < 50 x 10^3 /uL) 
 OTHER TYPE, SPECIFY: ________________________________________________________________________ 
  
 
 
CALCIUM METABOLIC DISORDERS 
  
 
 
CANCER, SPECIFY: ___________________________________________________________________________________ 
 
 
HAS THE SUBJECT RECEIVED OR WILL THE SUBJECT RECEIVE CHEMOTHERAPY WITHIN 30 DYAS PRIOR TO THE 
STUDY PROCEDURE?   YES 
   NO 
       
  
 
 
CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)/ CHRONIC LUNG DISEASE 
 
 
PLEASE INDICATE THE FEV1/FVC VALUE: 
 60-75% 
 50-59% 
 <50% 
 NOT AVAILABLE 
WHAT TREATMENT DID THE SUBJECT RECEIVE FOR THIS CONDITION? 
 CHRONIC INHALED OR ORAL BRONCHODILATOR THERAPY 
 CHRONIC STEROID THERAPY 
 OXYGEN OR VENTILATION 
 OTHER TREATMENT (SPECIFY) __________________________________________________________________ 
  
 
 
DIABETES 
 
 
                        
    TYPE 1 
                        
    TYPE 2 (INDICATE WHAT TREATMENT THE PATIENT IS RECEIVING) 
                                          
   NONE      
    DIET     
   ORAL     
   INSULIN 
  
 
 
OBESITY (BMI ≥ 30) 
  
 
 
LIVER DISEASE 
  
 
 
MUSCULOSKELETAL DYSFUNCTION 
 
 
DOES THE SUBJECT HAVE SEVERE IMPAIRMENT OF MOBILITY DUE TO THIS CONDITION?  YES 
   NO 
     
  
 
 
RENAL FAILURE / INSUFFICIENCY 
 
     
 
 
         DATE SUBJECT WAS DIAGNOSED:  
 
                                                             ___ ___ / ___  ___  ___  /  ___  ___  ___  ___  
                                                     D    D      M     M     M         Y     Y     Y      Y 
 
IF UNKNOWN, APPROXIMATELY HOW MANY MONTHS AGO WAS THE SUBJECT DIAGNOSED? ___________________ 
 
IF UNKNOWN, WAS THE SUBJECT DIAGNOSED > 5 YEARS AGO?  YES 
   NO 
       
 

 
 
           
 
MEDICAL HISTORY
PAGE 8 OF 8
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
YES 
   NO 
     SUBJECT CURRENTLY RECEIVING DIALYSIS 
 
 
 
   
 
 
OTHER DISEASE WHICH REQUIRES IMMUNOSUPPRESIVE THERAPY INHALED OR SYSTEMIC STEROID THERAPY OR 
CHEMOTHERAPY WITHIN 30 DAYS OF THE STUDY PROCEDURE 
   
    
 
 
SMOKER, CURRENT 
 
 
 
IF NO, WHEN DID SUBJECT QUIT: 
                        
     QUIT > 1 MONTH AGO 
                        
     QUIT ൑ 1 MONTH AGO 
    
 
 
ALCOHOL/DRUG ABUSE 
 
 
 
 
 
DATE 
 
 
 
 
 
  
 
 
 
SIGNATURE 
D 
D 
M 
M 
M 
 
Y 
Y 
Y 
Y 
 

 
          
 
QUALITY OF LIFE 
PAGE 1 OF 2 
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
1SF-12v2™ Health Survey© 1994, 2002 by QualityMetric incorporated and Medical Outcomes Trust. 
SF-12® a registered trademark of Medical Outcomes Trust. (SF12v2 Standard, US version 2.0). 
 
QualityMetric’s SF-12v2® Health Survey1 is a shorter version of the SF-36v2® Health Survey that uses just 12 
questions to measure functional health and well-being from the subject’s point of view.  It takes only 2-3 
minutes to complete.  The SF-12v2 is a practical, reliable, and valid measure of physical and mental health and 
covers the same eight health domains as the SF-36v2 with one or two questions per domain.  
 
 
Date of Assessment:                 ___ ___ / ___  ___  ___  /  ___  ___  ___  ___  
                                                                D     D       M    M     M         Y     Y     Y      Y  
1. In general, would you say your health is: 
 
Excellent 
1 
Very good 
2 
Good 
3 
Fair 
4 
Poor 
5 
 
2. The following questions are about activities you might do during a typical day.  Does your health now limit 
you in these activities?  If so, how much? 
 
 
 
 
Yes, limited a 
lot 
Yes, limited a 
little 
No, not 
limited at all 
a. Moderate activities, such as moving a 
table, pushing a vacuum cleaner, bowling, 
or playing golf. 
 
 
1 
 
2 
 
3 
b. Climbing several flights of stairs. 
1 
2 
3 
 
3. During the past 4 weeks, how much of the time have you had any of the following problems with your work or 
other regular daily activities as a result of your physical health? 
 
 
 
 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
a. Accomplished less than you 
would like. 
 
 
 
1 
 
2 
 
3 
 
4 
 
5 
b. Were limited in the kind of 
work or other activities. 
 
1 
2 
3 
4 
5 
4. During the past 4 weeks, how much of the time have you had any of the following problems with your work or 
other regular daily activities as a result of any emotional problems (such as feeling depressed or anxious)? 
                                                     
 

 
          
 
QUALITY OF LIFE 
PAGE 2 OF 2 
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
1SF-12v2™ Health Survey© 1994, 2002 by QualityMetric incorporated and Medical Outcomes Trust. 
SF-12® a registered trademark of Medical Outcomes Trust. (SF12v2 Standard, US version 2.0). 
 
 
 
 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
a. Accomplished less than you 
would like. 
 
 
1 
 
2 
 
3 
 
4 
 
5 
b. Did work or activities less 
carefully than usual? 
1 
2 
3 
4 
5 
 
 
5. During the past 4 weeks, how much did pain interfere with your normal work (including both work 
outside the home and housework)? 
Not at all 
1 
A little bit 
2 
Moderately 
3 
Quite a bit 
4 
Extremely 
5 
 
6. These questions are about how you feel and how things have been with you during the past 4 
weeks. For each question, please give one answer that comes closest to the way you have been 
feeling.  How much of the time during the past 4 weeks …… 
 
 
 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
a. Have you felt calm and 
peaceful? 
 
 
1 
 
2 
 
3 
 
4 
 
5 
b. Did you have a lot of energy? 
 
1 
2 
3 
4 
5 
c. Have you felt downhearted 
and depressed? 
1 
2 
3 
4 
5 
 
7. During the past 4 weeks, how much of the time has your physical health or emotional problems 
interfered with your social activities (like visiting friends, relatives, etc.)? 
All of the 
time 
1 
Most of the 
time 
2 
Some of the 
time 
3 
A little of the 
time 
4 
None of the 
time 
5 
 
 
 
DATE SIGNED 
 
 
 
 
 
 
 
 
 
 
 
SIGNATURE 
 
D 
D 
 
M 
M 
M 
 
Y 
Y 
Y 
Y 
 

 
 
       COMMENCETM TRIAL 
1
 
 
Subject Study ID  
201202  
 
 
- 
 
 
 
 
    Site# 
 
 
 
 
 
ECHO SITE TRACKING/EVALUATION 
Page 1 of 4
 
 
Study 2012‐02  
 
 
 
 
 
 
 
ECHO SITE TRACKING FORM 
Date ECHO exam 
 
 
/ 
 
 
 
/ 
 
 
 
 
(DD/MMM/YYYY) 
Name of the echocardiographer 
 
Echocardiograph equipment used (check one): 
 
GE Vivid 
 
Other GE, specify 
 
 
Philips IE33 
 
Other Philips, specify: 
 
 
Siemens 
 
Other model, specify: 
 
Please provide the following physical assessment parameters: 
Subject weight 
 
     kg            
     lb       
Heart rate 
 
bpm 
Blood pressure 
 
/ 
 
mmHg 
Cardiac rhythm (check one): 
       
     NSR          
     Afib           
     Paced       
     Indeterminate            
Miscellaneous 
Is subject enrolled in aortic or mitral arm of trial? 
       
    AORTIC          
     MITRAL           
Did the echocardiographer assess the study valve? 
       
     No          
     Yes            
Date echocardiographs shipped/uploaded to 
the Core Lab 
 
 
/ 
 
 
 
/ 
 
 
 
 
(DD/MMM/YYYY) 
Shipping 
Shipping method (check one): 
 
Images uploaded 

 
 
       COMMENCETM TRIAL 
2
 
 
Subject Study ID  
201202  
 
 
- 
 
 
 
 
    Site# 
 
 
 
 
 
ECHO SITE TRACKING/EVALUATION 
Page 2 of 4
 
 
Study 2012‐02  
 
 
 
 
 
 
 
 
Fed Ex 
 
UPS 
 
DHL 
 
Other provider, specify: 
 
Shipping tracking number: 
 
Comments: 
 
 
 
        DATE  
 
 
   
 
 
   
 
 
 
SIGNATURE 
 
D 
D 
  M  M  M    Y 
Y 
Y 
Y 
 
 
 

 
 
       COMMENCETM TRIAL 
3
 
 
Subject Study ID  
201202  
 
 
- 
 
 
 
 
    Site# 
 
 
 
 
 
ECHO SITE TRACKING/EVALUATION 
Page 3 of 4
 
 
Study 2012‐02  
 
 
 
 
 
 
 
ECHO SITE EVALUATION FORM 
Please indicate the results of the LVOT assessment:
Peak velocity 
 
m/sec 
    Not evaluable
Peak gradient 
 
mmHg 
    Not evaluable
Mean gradient 
 
mmHg 
    Not evaluable
VTI 
 
cm 
    Not evaluable
Please indicate the results of the AORTIC OR MITRAL valve assessment (complete section for trial arm position):
**Please only indicate results POST‐implant of the valve for the operative TEE 
Peak velocity 
 
m/sec 
    Not evaluable
Peak gradient 
 
mmHg 
    Not evaluable
Mean gradient 
 
mmHg 
    Not evaluable
VTI 
 
cm 
    Not evaluable
Annulus size 
 
cm 
    Not evaluable
Valve area 
 
cm2
    Not evaluable
Please indicate the AR severity: 
 
0 None 
 
+1 Trivial/Trace 
 
+2 Mild 
 
+3 Moderate 
 
+4 Severe 
 
Indeterminate 
Please indicate the MR severity: 
 
0 None 
 
+1 Trivial/Trace 
 
+2 Mild 
 
+3 Moderate 
 
+4 Severe 
 
Indeterminate 
LVEF 
 
% 
    Not evaluable
LVEF range (max, min) 
 
‐ 
 
%
    Not evaluable
 
 
 
 

 
 
       COMMENCETM TRIAL 
4
 
 
Subject Study ID  
201202  
 
 
- 
 
 
 
 
    Site# 
 
 
 
 
 
ECHO SITE TRACKING/EVALUATION 
Page 4 of 4
 
 
Study 2012‐02  
 
 
 
 
 
 
 
 
What method was used for LVEF? 
 
Single plane 
 
Biplane 
 
Quinones 
 
Visual 
Please indicate the severity of paravalvular leak (PVL) of the study valve: 
 
0 None 
 
+1 Trivial/Trace 
 
+2 Mild 
 
+3 Moderate 
 
+4 Severe 
 
Indeterminate 
 
Not applicable at baseline 
What was the assessment of RV function? 
 
Normal 
 
Mildly reduced 
 
Moderately reduced 
 
Severely reduced 
 
Indeterminate 
 
 
            DATE  
 
 
 
 
 
 
 
 
 
 
 
SIGNATURE 
 
D 
D 
 
M 
M 
M 
 
Y 
Y 
Y 
Y 
 
 
 
 
 
 
 

 
 
   COMMENCETM TRIAL – MODELS 11000A AND 11000M  
SURGERY
PAGE 1 OF 6
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
DATE OF HOSPITAL ADMISSION: 
  ___ ___ / ___  ___  ___  /  ___  ___  ___  ___  
                                                            
 
     D     D       M    M     M         Y     Y     Y      Y  
DATE OF SURGERY:                
 
   ___ ___ / ___  ___  ___  /  ___  ___  ___  ___  
                                     
         
 
     D     D       M    M     M         Y     Y     Y      Y  
 
IMPLANTING SURGEON: 
           ____________________________________________________ 
PREOPERATIVE CONDITION 
YES 
NO 
 
 
 
DID A MYOCARDIAL INFARCTION (MI) OCCUR WITHIN 21 DAYS PRIOR TO SURGERY? 
INDICATE THE TIME INTERVAL WHEN THE LAST MI OCCURRED: 
      
    <6 HOURS  
    6-24 HOURS  
    1-7 DAYS 
    8-21 DAYS 
 
 
 
WITHIN 2 WEEKS PRIOR TO THE SURGICAL PROCEDURE:  WAS THE SUBJECT IN CONGESTIVE HEART 
FAILURE? 
 
 
WITHIN 2 WEEKS PRIOR TO THE SURGICAL PROCEDURE:  DID THE SUBJECT EXPERIENCE AN 
ARRHYTHMIA? 
WAS THE OBSERVED ARRHYTHMIA CONSIDERED ATRIAL FIBRILLATION OR ATRIAL FLUTTER? 
    YES  
    NO 
 
 
WAS THE SUBJECT EXPERIENCING CARDIAC/CHEST PAIN AT ADMISSION? 
WHAT IS THE LIKELY CAUSE OF THESE SYMPTOMS? 
    STABLE ANGINA  
    UNSTABLE ANGINA  
    UNLIKELY DUE TO ISCHEMIA  
    NON-STEMI     
    STEMI 
 
 
DID THE SUBJECT RECEIVE IV INOTROPIC AGENTS WITHIN 48 HOURS PRECEDING SURGERY OR  
ADMINISTRATION OF THIS MEDICATION DOCUMENTED AS CONTRAINDICATED? 
DID THE SUBJECT EXPERIENCE OR REQUIRE ANY OF THE FOLLOWING AFTER ADMISSION BUT PRIOR TO GOING UNDER 
ANESTHESIA?:  
 
 
VENTRICULAR FIBRILLATION 
 
 
VENTRICULAR TACHYCARDIA 
 
 
CARDIOGENIC SHOCK 
 
 
ABORTED SUDDEN DEATH 
 
 
ACUTE RENAL FAILURE (ANURIA OR OLIGURIA <10 ML/HR) 
 
 
CARDIOPULMONARY RESUSCITATION < 1 HOUR PRIOR TO SURGERY 
 
 
VENTILATION PRIOR TO ARRIVAL IN THE ANESTHETIC ROOM 
 
 
INOTROPIC SUPPORT OR IABP 
 
 
ANOTHER CARDIAC INTERVENTION <6 HOURS PRIOR TO SCHEDULED SURGERY 
WHAT IS THE URGENCY OF THE SURGERY BEING PERFORMED?  (CHECK ONE) 

 
 
   COMMENCETM TRIAL – MODELS 11000A AND 11000M  
SURGERY
PAGE 2 OF 6
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
ELECTIVE 
 
URGENT 
 
SALVAGE 
 
EMERGENCY 
PLEASE CONFIRM THE DIAGNOSIS FOR THE CURRENT REPLACEMENT (CHECK ONE) 
 
STENOSIS 
 
STENOSIS  WITH INSUFFICIENCY 
 
PURE INSUFFICIENCY 
 
PROSTHETIC VALVE DYSFUNCTION 
 
OTHER DIAGNOSIS, SPECIFY: 
 
 
SURGICAL APPROACH (CHECK ONE) 
 
           FULL STERNOTOMY 
 
 
 
           MINI UPPER STERNOTOMY 
 
           RIGHT THORACOTOMY 
 
           OTHER MIS, SPECIFY: 
 
 
SURGICAL APPROACH AND ANNULUS PREPARATION 
WERE THE FOLLOWING CONCOMITANT PROCEDURES PERFORMED? 
YES 
NO 
 
 
 
CORONARY ARTERY BYPASS GRAFTNG (CABG = Distal 
anastomosis) 
 
 
 
 
 HOW MANY GRAFTS WERE DONE? 
     
    1      
    2      
    3      
    4+  
 
 

 
 
   COMMENCETM TRIAL – MODELS 11000A AND 11000M  
SURGERY
PAGE 3 OF 6
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
YES 
NO 
 
 
 
 PERMANENT PACEMAKER IMPLANT 
 
 
 
 
WAS CARDIAC RESYNCHRONIZATION TECHNIQUE (CRT) USED?         
 
     YES       
     NO 
 
WAS THIS PROCEDURE PLANNED? 
          
     YES       
     NO 
                          IF NO, WHY WERE TEMOPRARY PACER LINES NOT EMPLOYED?   
                          _____________________________________________________________________________________ 
 
 
AUTOMATED IMPLANTED CARDIOVERTER (AICD) IMPLANT  
 
 
 
WAS CARDIAC RESYNCHRONIZATION TECHNIQUE (CRT) USED?         
 
     YES       
     NO 
 
 
 
ATRIAL ABLATION 
 
 
 
 
WHAT TYPE OF ABLATION PROCEDURE WAS DONE? 
      
    PRIMARY EPICARDIAL 
      
    PRIMARILY INTRACARDIAC 
 
 
AORTIC ANEURYSM/ DISSECTION REPAIR 
 
 
ATRIAL SEPTAL DEFECT (ASD) REPAIR    
 
 
 
WHAT WAS THE TYPE OF DEFECT REPAIRED? 
      
    PATENT FORAMEN OVALE       
      
    SECUNDUM ASD 
      
   SINUS VENOSUS ASD 
      
    MULTIPLE DEFECTS 
 
 
ROOT SINUS ENLARGEMENT 
 
 
AORTIC ANNULAR ENLARGMENT 
 
 
 
 
 
 
 
WHAT METHOD WAS USED? 
      
    NICKS       
      
    MANOUGUIAN 
      
   KONNO 
 
 
TRICUSPID VALVE REPAIR  (WITH MITRAL VALVE REPLACEMENT) 
 
 
 
OTHER PROCEDURE, PLEASE SPECIFY:  
 
 
 

 
 
   COMMENCETM TRIAL – MODELS 11000A AND 11000M  
SURGERY
PAGE 4 OF 6
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
YES 
NO 
 
 
 
WERE ANY UNPLANNED PROCEDURES PERFORMED DURING THIS OPERATION? 
 
 
 
WHY WAS THIS PROCEDURE NECESSARY? 
      
    UNSUSPECTED SUBJECT DISEASE OR ANATOMY 
      
    SURGICAL COMPLICATION 
 
 
WAS AN INTRAAORTIC BALLOON PUMP (IABP) USED IN RELATION TO THIS SURGICAL 
PROCEDURE? 
? 
 
 
WHEN WAS THE IABP INSERTED? 
      
    PREOPERATIVELY 
      
    INTRAOPERATIVELY 
      
    POSTOPERATIVELY 
 
 
WAS ANNULAR DEBRIDEMENT PERFORMED? 
 
 
DEGREE: 
 
 
 
ROUTINE 
 
 
 
EXTENSIVE – NOT REQUIRING ANNULAR REPAIR  
 
 
 
EXTENSIVE – REQUIRING ANNULAR REPAIR/RECONSTRUCTION 
 
 
LOCATION: 
 
 
 
FULL ANNULAR CIRCUMFERENCE 
 
 
 
PARITAL ANNULAR CIRCUMFERENCE (>= 50%) 
 
 
 
PARTIAL ANNULAR CIRCUMFERENCE (<50%) 
 
 
CALCIFICATION REMOVAL: 
 
 
 
COMPLETE 
 
 
 
INCOMPLETE  (>= 50%) 
 
 
 
INCOMPLETE  (<50%) 
WHAT STUDY VALVE MODEL WAS EMPLOYED? (CHECK ONE) 
 
11000A 
 
11000M 
HOW MANY ATTEMPTS WERE MADE TO IMPLANT THE VALVE? (CHECK ONE) 
 
2 
 
1 
 
 

 
 
   COMMENCETM TRIAL – MODELS 11000A AND 11000M  
SURGERY
PAGE 5 OF 6
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
WHY WAS A SECOND ATTEMPT TO IMPLANT THE STUDY VALVE NOT PERFORMED?  
 
 
FIRST ATTEMPT SUCCESSFUL 
 
 
A STUDY VALVE OF THE CORRECT SIZE IS NOT AVAILABLE AT THE SITE 
 
 
NONE OF THE SIZES AVAILABLE FOR THE STUDY VALVE ARE SUITABLE FOR THE SUBJECT 
 
 
SURGEON CHOSE NOT TO ATTEMPT TO IMPLANT THE STUDY VAVLE AGAIN DUE TO A MEDICAL 
COMPLICATION 
 
 
OTHER REASON: SPECIFY: 
 
WAS THE HEART RESTARTED WITH THE STUDY VALVE IMPLANTED? 
 
NO 
 
WAS A COMMERCIAL VALVE SUCCESSFULLY IMPLANTED? 
 
 
NO (PLEASE FILL OUT A STUDY EXIT FORM) 
 
 
YES 
 
 
PLEASE PROVIDE THE FOLLOWING INFORMATION ABOUT THE COMMERCIAL VALVE: 
 
 
MANUFACTURER AND MODEL: 
 
 
 
VALVE SIZE (MM): 
 
 
 
SERIAL NUMBER: 
 
 
YES 
 
WAS A POST-IMPLANT TRANSESOPHAGEAL ECHOCARDIOGRAM PERFORMED? 
 
 
NO 
 
 
YES 
 
 
TIME ECHOCARDIOGRAM STARTED: 
 
 
: 
 
 
(24 HR FORMAT) 
 
 
WHAT TYPE OF ECHOCARDIOGRAM WAS DONE? 
      
    TEE     
    TTE 
 
 
WAS ANY OBSERVED REGURGITATON CLINICALLY ACCEPTABLE? 
      
    NO       
    YES 
 
WAS SERUM GLYCEROL ANALYSIS REQUIRED FOR THIS SUBJECT? 
      
    NO       
    YES 

 
 
   COMMENCETM TRIAL – MODELS 11000A AND 11000M  
SURGERY
PAGE 6 OF 6
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
WAS A POST-OPERATIVE ELECTROCARDIOGRAM PERFORMED UPON ARRIVAL TO THE ICU? 
      
    NO       
    YES 
YES 
NO 
 
 
 
WAS THERE A BLEEDING-RELATED REOPERATION WITHIN THE FIRST 24 HOURS AFTER SURGERY? 
 
 
DID ANY ADVERSE EVENTS OCCUR DURING SURGERY? 
IF YES, COMPLETE ADVERSE EVENT (AE) FORM (S) 
 
SURGICAL PROCEDURE TIMING 
SKIN INCISION:                        
 
: 
 
 
(24 HR FORMAT) 
START ECC (PUMP):               
 
: 
 
 
(24 HR FORMAT) 
START CROSS CLAMP:          
 
: 
 
 
(24 HR FORMAT) 
START SIZING:                         
 
: 
 
 
(24 HR FORMAT) 
REMOVAL CROSS CLAMP:     
 
: 
 
 
(24 HR FORMAT) 
END ECC (PUMP):                   
 
: 
 
 
(24 HR FORMAT) 
SKIN CLOSURE:                       
 
: 
 
 
(24 HR FORMAT) 
 
COMMENTS: 
 
 
 
 
 
 
DATE SIGNED
 
 
 
 
 
 
 
 
 
 
 
 SIGNATURE 
 
D 
D 
 
M 
M 
M 
 
Y 
Y 
Y 
Y 
 
 

 
 
   COMMENCETM TRIAL – MODELS 11000A AND 11000M  
NATIVE AORTIC VALVE CONDITION
PAGE 1 OF 1
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
AORTIC VALVE ETIOLOGY  
YES 
NO 
 
 
 
DEGENERATIVE 
 
 
 
DYSTROPHIC CALCIFICATION 
 
 
CONGENITAL 
 
 
RHEUMATIC 
 
 
REMOTE ENDOCARDITIS 
 
 
OTHER ETIOLOGY, SPECIFY: 
 
CONDITION OF THE AORTIC VALVE AND SURROUNDING ANATOMY 
YES 
NO 
 
 
 
WAS CALCIFICATION OBSERVED? 
 
 
YES 
NO 
 
 
 
 
 
ANNULUS 
 
 
 
 
LEAFLETS          
 
 
 
 
AORTIC WALL 
 
 
 
 
CORONARY ARTERIES 
 
 
 
 
LEAFLET FUSION  
 
 
 
 
LEAFLET PERFORATION 
 
 
 
 
MYXOMATOUS (LEAFLET) 
 
 
 
 
VEGETATION 
 
 
 
 
CONGENITAL VALVE DEFECT 
 
 
 
 
      
    BICUSPID AORTIC VALVE 
      
    UNICUSPID AORTIC VALVE     
 
 
 
 
OTHER DISEASE CONDITION, SPECIFY:_______________________________________________ 
 
COMMENTS: 
 
 
 
 
 
 
DATE SIGNED
 
 
 
 
 
 
 
 
 
 
 
 SIGNATURE 
 
D 
D 
 
M 
M 
M 
 
Y 
Y 
Y 
Y 
 
 

 
 
   COMMENCETM TRIAL – MODELS 11000A AND 11000M  
NATIVE MITRAL VALVE CONDITION
PAGE 1 OF 2
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
MITRAL VALVE ETIOLOGY  
YES 
NO 
 
 
 
DEGENERATIVE 
 
 
 
DYSTROPHIC CALCIFICATION 
 
 
FUNCTIONAL DISEASE 
 
 
CONGENITAL 
 
 
RHEUMATIC 
 
 
REMOTE ENDOCARDITIS 
 
 
ISCHEMIC HEART DISEASE 
 
 
MITRAL VALVE PROLAPSE 
 
 
       
    ANTERIOR 
       
    POSTERIOR 
       
    BILEAFLET 
 
 
OTHER ETIOLOGY, SPECIFY: 
 
CONDITION OF THE MITRAL VALVE AND SURROUNDING ANATOMY 
YES 
NO 
 
 
 
WAS CALCIFICATION OBSERVED? 
 
 
YES 
NO 
 
 
 
 
 
ANNULUS 
 
 
 
 
       
    ANTERIOR 
       
    POSTERIOR 
       
    BILATERAL 
 
 
 
 
LEAFLETS          
 
 
 
 
       
    ANTERIOR 
       
    POSTERIOR 
       
    BILEAFLET 
 
 
 
 
CHORDAE TENDINAE 
 
 
 
 
PAPILLARY MUSCLE 
 
 
 
 
DILATED ANNULUS 
 
 
 
 
LEAFLET FUSION 
 
 
 
 
LEAFLET PERFORATION 
 
 
 
 
MYXOMATOUS (LEAFLET) 
 
 
 
 
FIBROELASTIC DEFICIENCY 
 
 
 
 
VEGETATION 
 
 
 
 
CONGENITAL MITRAL VALVE DEFECT 
 
 

 
 
   COMMENCETM TRIAL – MODELS 11000A AND 11000M  
NATIVE MITRAL VALVE CONDITION
PAGE 2 OF 2
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
 
YES 
NO 
 
 
 
 
 
CHORDAE DYSFUNCTION 
 
 
 
 
       
    ELONGATED 
       
    TETHERED 
       
    RUPTURED 
 
 
 
 
OTHER DISEASE CONDITION, SPECIFY:_______________________________________________ 
MITRAL VALVE REPLACEMENT TECHNIQUE 
 
 ANTERIOR LEAFLET 
             
    COMPLETE PRESERVATION 
             
   PARTIAL PRESERVATION 
             
   COMPLETE REMOVAL 
POSTERIOR  LEAFLET 
             
    COMPLETE PRESERVATION 
             
   PARTIAL PRESERVATION 
             
   COMPLETE REMOVAL 
ANTERIOR CHORDS 
             
   PRESERVED 
             
   REMOVED 
POSTERIOR CHORDS 
             
   PRESERVED 
             
   REMOVED 
 
 
        
 
 
 
 
 
 
COMMENTS: 
 
 
 
 
 
 
DATE SIGNED
 
 
 
 
 
 
 
 
 
 
 
 SIGNATURE 
 
D 
D 
 
M 
M 
M 
 
Y 
Y 
Y 
Y 
 
 

 
 
     COMMENCETM TRIAL –  
1
 
 
Subject Study ID  
201202  
 
 
- 
 
 
 
 
    Site# 
 
 
 
 
 
DEVICE PERFORMANCE 
Page 1 of 2
 
 
Study 2012‐02  
 
 
 
 
 
 
 
What study valve implant attempt was being performed?                      
     1st attempt            
     2nd attempt     
Please provide the following information about the study valve: 
Valve size: 
     19mm            
     21mm          
     23mm           
     25mm          
     27mm            
     29mm            
     31mm          
       33mm 
Serial Number: 
 
What type of sizer was used? 
 
Model 1133 [AORTIC] 
 
Model 1173  [MITRAL] 
 
Universal sizer 
 
Other sizer, specify: 
 
What was the barrel size of the valve sizer? 
 
mm 
What suture technique was used to secure the valve (check one)? 
 
Single simple interrupted without pledgets 
 
Horizontal interrupted mattress without pledgets (intra‐annular) 
 
Horizontal interrupted without pledgets (supra‐annular) 
 
Horizontal interrupted with pledgets (intra‐annular) 
 
Horizontal interrupted with pledgets (supra‐annular) 
 
Continuous running sutures without pledgets/strip 
 
Continuous running sutures with pledgets/strip 
 
Interrupted figure of eight without pledgets 
 
Other technique, specify: 
 
 
Not attempted 
How was the valve positioned?          
     Supra‐annular            
     Intra‐annular          
     Not attempted 
Did the study valve perform as intended?          
     No            
     Yes           
 
Please indicate the types of valve failures observed (select all that apply): 

 
 
     COMMENCETM TRIAL –  
2
 
 
Subject Study ID  
201202  
 
 
- 
 
 
 
 
    Site# 
 
 
 
 
 
DEVICE PERFORMANCE 
Page 2 of 2
 
 
Study 2012‐02  
 
 
 
 
 
 
 
 
 
Device function, unable to place sutures through the sewing ring 
 
 
Device function, unable to position on the aortic annulus 
 
 
Device function, bioprosthesis and holder separate during procedure 
 
 
Device function, other, specify: 
 
 
 
Device use, sizing technique 
 
 
Device use, sterility compromised 
 
 
Device use, used expired product 
 
 
Device use, component damaged by operator 
 
 
Device use, improper postioning 
 
 
Device use, other, specify: 
 
DEVICE TECHNICAL SUCCESS 
Was the heart restarted with the valve in place after this implant attempt?          
     No            
     Yes           
Did the subject leave the operating room with the study valve in place for this attempt?          
     No            
     Yes           
 
If No, Why did the implant attempt fail? 
 
 
Valve failure (Please indicate the valve failure type on this form) 
 
 
Subject died 
 
 
Other reason, specify: 
 
Please provide the time at which each step in the study device procedure occurred in HH:MM:SS format: 
Start of study procedure (first stitch placed)                                
 
:  
 
:
 
 
     Not attempted             
     Not available           
First stitch placed on valve ring                      
 
 
:  
 
:
 
 
     Not attempted             
     Not available           
Complete the study procedure (last stitch tied down on the 
valve)                 
 
 
:  
 
:
 
 
     Not attempted             
     Not available           
Comments: 
 
 
DATE 
SIGNED 
 
 
   
 
 
   
 
 
 
SIGNATURE 
 
D  D    M  M  M    Y 
Y 
Y 
Y 
 

 
 
            
 
DISCHARGE
PAGE 1 OF 1
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
 
 
VISIT TYPE: 
 DISCHARGE           
 10 DAY FOLLOW UP (ECHO REQUIRED)         
 
 
DATE OF DISCHARGE:  ___  ___ / ___  ___  ___  /  ___  ___  ___  ___  
                                                      D    D       M    M     M         Y     Y     Y      Y  
 
DISCHARGED TO:  
         
 HOME 
         
 ANOTHER HOSPITAL 
         
 EXTENDED CARE 
 
POST OPERATIVE HOSPITALIZATION INFORMATION 
 
 DURATION OF TIME IN INTENSIVE CARE UNIT  
 
                            __________ DAYS  AND ____________HOURS 
 DURATION FO TIME IN INTERMEDIATE CARE / HIGH DEPENDENCY UNIT  __________ DAYS  AND ____________HOURS      
DURATION OF TIME IN GENERAL WARD  
    
                            __________ DAYS  AND ____________HOURS 
      
******COMPLETE ASSESSMENT FORM******** 
  
 
 
 
DATE SIGNED  
 
 
 
 
 
 
 
 
 
 
SIGNATURE 
 
D 
D 
 
M 
M 
M 
 
Y 
Y 
Y 
Y 
 

 
 
       
ADVERSE EVENT
PAGE 1 OF 3
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
 
 
 
RECORD ONLY ONE ADVERSE EVENT PER FORM 
1. 
EVENT ONSET DATE 
 
 
 
 
 
 
 
 
 
  
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
 
 
 
 
 
 
 
 
 
2. 
SITE AWARENESS DATE 
 
 
 
 
 
 
 
 
 
 
  
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
 
 
 
 
 
 
 
 
 
3. 
TIMING OF EVENT ONSET 
 
 INTRA-OPERATIVE 
 
 POST-OPERATIVE 
 
4. 
IS THIS A NEW OR WORSENING ADVERSE EVENT? 
 NEW 
 
 WORSENING 
 
5. 
EVENT NAME             
    (SEE ADVERSE EVENT LISTING*) 
 
 
6. 
EVENT SUMMARY  
 
 
 
 
 
7. 
METHOD OF DETECTION (CHECK ALL THAT APPLY) 
 LAB FINDING 
 ECHO 
 ANGIOGRAM 
 MRI 
ECG 
 AUTOPSY 
 OBSERVATION 
 EXAM 
 REOPERATION 
 (Date of reoperation:__________________ (DD/MMM/YYYY)
 
     
 OTHER (SPECIFY) 
  
 
 
 
DATE OF TEST/ EXAM: _________________________________ 
 
 
 
 
8. 
CAUSALITY: IS THIS EVENT RELATED TO ANY OF THE FOLLOWING? 
9.
DID ANTITHROMBOEMBOLIC MEDICATION 
CONTRIBUTETO EVENT? 
SURGICAL PROCEDURE 
 YES 
 NO 
 UNDETERMINED 
 YES     
 NO 
 
 
 
 
  
 ANTICOAGULANT MEDICATION 
STUDY VALVE 
 YES 
 NO 
 UNDETERMINED 
  
 ASPIRIN 
STUDY VALVE PROCEDURE 
 YES 
 NO 
 UNDETERMINED 
 OTHER ANTIPLATELET MEDICATION 
USER ERROR 
 YES 
 NO 
 UNDETERMINED 
 OTHER ANTITHROMBOEMBOLIC 
MEDICATION: ___________________________ 
DEFICIENCY IN INSTRUCTIONS 
 YES 
 NO 
 UNDETERMINED 
 
WAS THIS MEDICATION PRESCRIBED DUE TO 
THE IMPLANT? 
UNDERLYING CONDITION 
 YES 
 NO 
 UNDETERMINED 
             
 YES                        
 NO 
 
 
     IF YES, WHAT WAS THE UNDERLYING CONDITION:  ___________________________________ 
DID NON- ANTITHROMBOEMBOLIC MEDICATION 
CONTRIBUTE TO EVENT? 
 
 YES                        
 NO 
10. SERIOUS ADVERSE EVENT 
 YES 
 NO 
            IF YES, SPECIFY:___________________ 
 RESULTED IN DEATH 
 RESULTED IN LIFE-THREATENING ILLNESS OR INJURY 
 RESULTED IN PERMANENT IMPAIRMENT 

 
 
       
ADVERSE EVENT
PAGE 2 OF 3
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
 
 
 
 RESULTED IN HOPSITALIZATION OR PROLONGING OF CURRENT HOSPITALIZATION 
 RESULTED IN SURGICAL INTERVENTION TO PREVENT PERMANENT IMPAIRMENT TO BODY STRUCTURE OR FUNCTION 
 RESULTED IN FETAL DISTRESS OR DEATH, CONGENITAL ABNORMALITY OR BIRTH DEFECT 
 RESULTED IN MEDICAL INTERVENTION TO PREVENT PERMANENT IMPAIRMENT TO BODY STRUCTURE OR FUNCTION 
 
UNANTICIPATED DEVICE 
RELATED ADVERSE DEVICE 
EFFECT? 
 YES 
 NO 
 
 
 
11. ACTION TAKEN/TREATMENT (MULTIPLE RESPONSES POSSIBLE) 
 
 CARDIOVERSION 
 
 TRANSFUSION 
 
 IF YES, NUMBER OF PRBC UNITS TRANSFUSED______________________ 
 
 MEDICATION GIVEN, SPECIFY 
 
 PACEMAKER/ICD IMPLANT (NOT PLANNED PRIOR TO AVR  - PROVIDE DATE) __________________________ (DD/MMM/YYYY) 
 PROLONGED HOSPITALIZATION 
 
 RE-HOSPITALIZATION REQUIRED 
 
  
ADMISSION DATE:    __________________________ (DD/MMM/YYYY) 
 
  
IF SUBJECT DISCHARGED, DISCHARGE DATE:  __________________________ (DD/MMM/YYYY) 
 
 SURGICAL INTERVENTION, REOP ON STUDY VALVE OR OTHER INTERVENTION ON STUDY VALVE  (COMPLETE EXPLANT REPORT) 
 
 
 
 
 
 OTHER INVASIVE INTERVENTION  (NOT REOPERATION ON STUDY VALVE) 
 
 
 
 
 
 
 
 
 
 (SPECIFY BELOW – PROVIDE DATE) 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
 SPECIFY OTHER INVASIVE INTERVENTION  
 
12. OUTCOME 
 
 ONGOING 
 UNRESOLVED AT STUDY EXIT 
 UNKNOWN AT STUDY EXIT 
 CHRONIC CONDITION 
 
 
 
 
 
 RESOLVED WITH OUT SEQUELAE  
DATE:
 
 
 
 
 
 
 
 
 
  
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 RESOLVED WITH SEQUELAE 
DATE:
 
 
 
 
 
 
 
 
 
  
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
 
 
DEATH  (PRIMARY CAUSE) 
 
 
 DEATH  (NOT PRIMARY CAUSE) 
 
  
 
DATE SIGNED
 
 
 
 
 
  
 
 
 
SIGNATURE 
 
D 
D 
 
M 
M 
M 
Y 
Y 
Y 
Y 
 
 
 
 
 
 
 
 
 
 
 

 
 
       
ADVERSE EVENT
PAGE 3 OF 3
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*AE Categories include: 
Blood and lymphatic (including ALL bleeding complications) 
Cardiovascular –Arrhythmia 
Cardiovascular - Regurgitation  
Cardiovascular - Stenosis  
Cardiovascular - Embolic Event/Valve Thrombosis  
Cardiovascular - Misc  
Device Dysfunction  
Gastrointestinal/Hepatic  
Genitourinary/Renal  
Pulmonary/Respiratory  
Peripheral Vascular  
Psychiatric  
Muscular Skeletal/Dermatologic  
Nonspecific or Unknown Body System  
 
Select ONE Adverse event from listing in applicable category 
 

 
 
      
DEVICE REOP_EXPLANT FORM
PAGE 1 OF 1
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
DATE OF REOPERATION/ REMOVAL/ EXPLANT 
  
___ ___ / ___  ___  ___  /  ___  ___  ___  ___  
                               
 
                                                                   D     D      M    M     M         Y     Y     Y      Y  
SURGERY OCCURRED AT INVESTIGATIONAL CENTER: 
    YES 
    NO 
TYPE OF PROCEDURE PERFORMED: 
 
 
 
 
    EXPLANT 
        
 
 
    VALVE IN VALVE REPLACEMENT:   
 
 
 
 
MANUFACTURER and MODEL:_____________________________ SIZE (MM): ___________ 
 
                                 
    OTHER, SPECIFY: _________________________________________________________________________ 
EXPLANT PROCEDURE 
    NAP 
 
 
WHAT WAS THE SURGICAL APPROACH USED FOR THE EXPLANT PROCEDURE? 
    FULL STERNOTOMY 
 
 
    RIGHT THORACOTOMY 
    MINI UPPER STERNOTOMY  
 
    NOT AVAILABLE 
WHAT TYPE OF AORTOTOMY WAS PERFORMED? _________________________________________________________ 
WHAT WAS REMOVED?    
    NOT AVAILABLE 
 
 
    BIOPROSTHESIS LEAFLETS 
 
 
    BIOPROSTHESIS SEWING RING 
 
 
 
WAS A ROOT ABSCESS PRESENT AT REOPERATION?       
 NO  
YES 
 
EASE OF STUDY VALVE EXPLANT: 
1  
2  
3  
4  
5  
N/A             (5 is the easiest/best) 
 
 
WAS A REPLACEMENT VALVE IMPLANTED? 
 NO 
YES   MANUFACTURER and MODEL:_______________________________  SIZE (MM): ___________ 
DEVICE GROSS EVALUATION (APPEARANCE OF VALVE PRIOR TO OR IMMEDIATELY FOLLOWING EXPLANT) 
ANSWER EACH YES OR NO 
YES 
NO 
 
 
 
 
THROMBUS 
 
 
 
 
VEGETATION 
 
 
 
SUTURE INTERFERENCE 
 
 
 
CALCIFICATION 
 
 
 
FIBROSIS 
 
 
 
DEHISCENCE 
 
 
 
OTHER, SPECIFY: 
 
DID EXCISION OF STUDY VALVE REQUIRE OR RESULT IN STRUCTURAL CHANGES? 
 NOT AVAILABLE 
 NO 
YES, SPECIFY: ____________________________________________________________________________         
WAS EXPLANTED STUDY VALVE RETURNED? 
 NO     
YES, RGA#: __________________________________ 
 
 
DATE SIGNED
 
 
 
SIGNATURE 
 
D
D
M 
M 
M 
Y
Y
Y
Y
 

 
 
  
 
STUDY EXIT
PAGE 1 OF 1
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
A. DATE OF STUDY EXIT 
 
 
 
__ 
__ 
/ 
__ 
__ 
__ 
/ 
__ 
__ 
__ 
__ 
 
 
 
D 
D 
 
M 
M 
M 
 
Y 
Y 
Y 
Y 
B. REASON FOR EXIT (SELECT ONE) 
 
 
1. 
SUBJECT COMPLETED PROTOCOL REQUIRED FOLLOW UPS 
 
 
 
 
2. 
SUBJECT DID NOT RECEIVE STUDY VALVE DURING THE INDEX PROCEDURE AND COMPLETED THE PROTOCOL 
REQUIRED FOLLOW-UP PERIOD 
3. 
STUDY VALVE EXPLANTED AND SUBJECT COMPLETED THE PROTOCOL REQUIRED FOLLOW-UP PERIOD 
4. 
SUBJECT MET AN EXCLUSION CRITERION AFTER STUDY ENROLLMENT 
 
5. 
SUBJECT VOLUNTARY WITHDREW OR SUBJECT WITHDRAWN BY INVESTIGATOR 
 
 
a. 
 
POST STUDY PROCEDURE BUT PRIOR TO DISCHARGE 
 
 
b. 
 
POST DISCHARGE FROM THE HOSPITAL 
 
 
 
PLEASE INDICATE THE REASON FOR WITHDRAWAL: 
 
 
 
 
______________________________________________________________________________________ 
 
 
6. 
SUBJECT LOST TO FOLLOW-UP    (SUBJECT MISSED 2 SEQUENTIAL FOLLOW-UP VISITS) 
 
 
 
7. 
DEATH 
 
A. 
   DATE OF DEATH      _ _ / _ _ _ / _ _ _ _ (DD/MMM/YYYY) 
 
    B.      DID THE SUBJECT DIE INTRAOPERATIVELY DURING THE STUDY PROCEDURE?  
 YES  
  NO 
 
    C.      DID THE SUBJECT DIE PRIOR TO DISCHARGE FROM THE HOSPITAL AFTER THE STUDY          
                PROCEDURE?              
 YES  
  NO 
   
    D.      CAUSE OF DEATH:____________________________________________________________________ 
 
               DATE REPORTED TO SPONSOR: _________________________ (DD/MMM/YYYY) 
 
PLEASE PROVIDE THE FOLLOWING INFORMATION ABOUT THE SUBJECT’S HOSPITALIZATION AFTER THE STUDY VALVE 
PROCEDURE: 
 
DURATION AND TIME IN THE INTENSIVE CARE UNIT (ICU)       ____________DAYS AND _________HOURS 
 
DURATION AND TIME IN THE INTERMEDIATE CARE/ HIGH DEPENDENCY UNIT 
 
                                                                                                            ____________DAYS AND _________HOURS 
 
DURATION AND TIME IN THE GENERAL WARD                             ____________DAYS AND _________HOURS 
   
 
 DATE OF AUTOPSY:__________________________(DD/MMM/YYYY)     
  NOT APPLICABLE 
 
                  WAS A STUDY VALVE REMOVED AT AUTOPSY? 
 YES  
  NO   
                                                                                                      (IF YES, FILL OUT REOP_EXP FORM) 
 
 
 
8. 
OTHER REASON, SPECIFY: _______________________________________________________________________ 
 
 
 
 
DATE SIGNED 
 
 
 
 
 
 
 
 
 
 
 
SIGNATURE 
 
D 
D 
 
M 
M 
M 
 
Y 
Y 
Y 
Y 
 

 
 
         
 
PROTOCOL
DEVIATION
PAGE 1 OF 1
 
 
Subject Study ID  201202  
 
 
- 
 
 
 
 
Site#  
 
 
 
 
 
 
 
1. 
DATE OF DEVIATION:  
       __   __/ ___  ___  ___  /  ___  ___  ___  ___  
                                                        D    D     M    M     M         Y     Y     Y      Y  
 
2. 
PLEASE SELECT PROTOCOL DEVIATION CODE  (PROTOCOL DEVIATION CODE LIST) 
EVENT CODE: 
________________ 
IF MISSED VISIT, SPECIFY: 
1st ATTEMPTED CONTACT          __________________________________________(DD/MMM/YYYY), TIME (HH:MM) 
 
 2nd ATTEMPTED CONTACT          _________________________________________(DD/MMM/YYYY), TIME (HH:MM) 
 
3rd ATTEMPTED CONTACT          ___________________________________________(DD/MMM/YYYY), TIME (HH:MM) 
 
CAN YOU CONFIRM THROUGH ANY SOURCES THAT THE SUBJECT IS ALIVE?    
 No       
 Yes 
IF OTHER DEVIATION, SPECIFY: 
_____________________________________________________________________________________ 
 
3. 
REASON: 
 
 
 
    NOT ORDERED BY PHYSICIAN 
        
 
    OVERSIGHT 
 
 
    PATIENT NOT AVAILABLE 
 
 
    PATIENT TOO SICK TO HAVE TEST 
 
 
    OTHER, SPECIFY: 
____________________________________________________________________________________ 
4. 
CORRECTIVE ACTION: 
    STUDY STAFF RE-TRAINED 
 
    OTHER, SPECIFY: 
____________________________________________________________________________________ 
 
 
 
DATE SIGNED
 
 
 
SIGNATURE 
 
D
D
M 
M 
M 
Y
Y
Y
Y
 
 

 
EDWARDS 
          TRIAL NUMBER 2012-02 
COMMENCETM TRIAL  
1 O
 
 
Subject Study ID  
201202  
 
 
- 
 
 
 
 
    Site#  
 
 
 
 
 
ECHO CORE LAB EVALUATION 
Page 1 of 10
 
 
Study 2012‐02  
 
 
 
 
 
 
 
ECHO CORE LAB TRACKING FORM 
Date ECHO received by core lab 
 
 
/ 
 
 
 
/ 
 
 
 
 
(DD/MMM/YYYY) 
Date of readability assessment 
 
 
/ 
 
 
 
/ 
 
 
 
 
(DD/MMM/YYYY) 
Please indicated whether or not the images were readable (check one): 
 
 
Readable 
 
 
Partially readable 
 
 
Not readable 
 
 
Was a request sent to the site to resend the images? 
     No         
     Yes        
 
 
 
Date of resend request: 
 
 
/ 
 
 
 
/ 
 
 
 
 
(DD/MMM/YYYY) 
 
 
Was the readability issue resolved? 
     No         
     Yes       
 
 
 
Date readability issue resolved: 
 
 
/ 
 
 
 
/ 
 
 
 
 
(DD/MMM/YYYY) 
Was the ECHO assessed by the core lab? 
     No         
     Yes       
 
 
 

 
EDWARDS 
          TRIAL NUMBER 2012-02 
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2 O
 
 
Subject Study ID  
201202  
 
 
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    Site#  
 
 
 
 
 
ECHO CORE LAB EVALUATION 
Page 2 of 10
 
 
Study 2012‐02  
 
 
 
 
 
 
 
ECHO CORE LAB EVALUATION 
Physical Assessment 
Subject weight 
 
     kg            
     lb       
Body Surface Are (BSA) 
 
m2 
     Not evaluable 
Heart rate 
 
bpm 
Blood pressure 
 
/ 
 
mmHg 
Does the ECHO indicate the subject has the following cardiac rhythm/conducting system disturbances? 
No 
Yes 
Indeterminate 
 
 
 
 
Normal sinus rhythm 
 
 
 
Atrial fibrillation 
 
 
 
Atrial flutter 
 
 
 
Ventricular tachycardia 
 
 
 
Ventricular fibrillation 
 
 
 
AV Block 
 
 
 
Please indicate the degree: 
     1st            
     2nd           
     3rd          
     Unknown            
 
 
 
Bundle branch block 
 
Please specify the location: 
     Left            
     Right           
     Not evaluable           
  
            
                    
 
Paced rhythm 
Please specify the location: 
     Atrial           
     Ventricular           
     Atrioventricular           
Valve Assessment:  Stenosis 
Please indicate the level of aortic stenosis (check one): 
 
None 

 
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          TRIAL NUMBER 2012-02 
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    Site#  
 
 
 
 
 
ECHO CORE LAB EVALUATION 
Page 3 of 10
 
 
Study 2012‐02  
 
 
 
 
 
 
 
 
Mild 
 
Moderate 
 
Severe 
 
Not evaluable 
Is there mitral stenosis? 
 Yes 
 No 
If Yes,  
 
Mild 
 
Moderate 
 
Severe 
 
Not evaluable 
Etiology of mitral stenosis: 
 
Calcific 
 
Rheumatic 
 
Other: Specify ___________________________________________________________ 
 
Indeterminate 
LV Structure/Regional Function 
Please indicate if any of the following abnormalities were observed: 
No 
Yes 
 
 
 
LV aneurysm 
 
 
     Please specify the location: 
 
 
 
Wall motion abnormality 
 
 
     Please specify: 
 
 
 
Cavity dilation 

 
EDWARDS 
          TRIAL NUMBER 2012-02 
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Subject Study ID  
201202  
 
 
- 
 
 
 
 
    Site#  
 
 
 
 
 
ECHO CORE LAB EVALUATION 
Page 4 of 10
 
 
Study 2012‐02  
 
 
 
 
 
 
 
 
 
Apical and/or left atrial thrombi 
 
 
    Please specify: 
 
 
 
Other abnormality 
Global LV Structure/Function 
What method of calculation was used for LV function assessment (check one)? 
 
Biplane 
 
Single 
 
Quinones 
 
Visual 
LVEDV 
 
ml 
     Not evaluable 
LVESV 
 
ml 
     Not evaluable 
LVEF 
 
% 
     Not evaluable 
LV Dimension 
Septal thickness (end‐diastolic) 
 
cm 
     Not evaluable 
Posterior wall thickness (end‐diastolic) 
 
cm 
     Not evaluable 
LV end‐diastolic dimension 
 
cm 
     Not evaluable 
LV end‐systolic dimension 
 
cm 
     Not evaluable 
LV mass 
 
g 
     Not evaluable 
LV mass index (BSA Corrected LV Mass) 
 
g/m2 
     Not evaluable 
Left Atrium (LA) 
 
mm 
     Not evaluable 
Aortic Dimensions 
LVOT diameter 
 
cm 
     Not evaluable 
Aortic annulus 
 
cm 
     Not evaluable 
Aortic root diameter 
 
cm 
     Not evaluable 

 
EDWARDS 
          TRIAL NUMBER 2012-02 
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5 O
 
 
Subject Study ID  
201202  
 
 
- 
 
 
 
 
    Site#  
 
 
 
 
 
ECHO CORE LAB EVALUATION 
Page 5 of 10
 
 
Study 2012‐02  
 
 
 
 
 
 
 
STJ diameter 
 
cm 
     Not evaluable 
Valve Assessment:  Measurements 
Please fill out this section for the Trial arm position 
Vpeak 
 
m/sec 
     Not evaluable 
TVI  
 
cm 
     Not evaluable 
Peak gradient (by continuous wave) 
 
mmHg 
     Not evaluable 
Mean gradient (by continuous wave) 
 
mmHg 
     Not evaluable 
TVI (LVOT) 
 
cm 
     Not evaluable 
Maximum V(LVOT) 
 
m/sec 
     Not evaluable 
Mean V(LVOT) 
 
m/sec 
     Not evaluable 
Stroke volume  
[LVOT derived for aortic position; across mitral 
valve for mitral position] 
 
ml 
     Not evaluable 
Transvalvular flow 
 
mL/s 
     Not evaluable 
Cardiac output (LVOT derived) 
 
L/min 
     Not evaluable 
Cardiac index 
 
L/min/m2 
     Not evaluable 
EOA (continuity equation) 
 
cm2 
     Not evaluable 
EOA index 
 
cm2/m2 
     Not evaluable 
Performance index 
 
cm2/cm2 
     Not evaluable 
Valve Assessment:  Regurgitation 
Please fill out this section for the Trial arm position 
Please identify all the methods of calculation used: 
No 
Yes 
 
 
 
Color doppler 
 
 
Regurgitant fraction 
 
 
Proximal convergent flow 

 
EDWARDS 
          TRIAL NUMBER 2012-02 
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Subject Study ID  
201202  
 
 
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    Site#  
 
 
 
 
 
ECHO CORE LAB EVALUATION 
Page 6 of 10
 
 
Study 2012‐02  
 
 
 
 
 
 
 
 
 
Continuous wave Doppler (pressure half‐time, only applicable to aortic regurgitation) 
 
 
Aortic/pulmonary flow reversal 
Please indicate the paravalvular leak severity: 
 
0 None 
 
+1 Trivial/Trace 
 
+2 Mild 
 
+3 Moderate 
 
+4 Severe 
 
Not evaluable 
 
Not applicable 
If the paravalvular leak severity is +2, +3, or +4, please indicate the following: 
 
Number of jets:  
     1          
     2           
     3       
     4           
     Other, specify:      
 
Please indicate the location of the jets: 
 
 
Please indicate the image view of the jets:        
     PLAX          
     PSAX           
     A5C       
     A3C            
Please indicate the transvalvular leak severity: 
 
0 None 
 
+1 Trivial/Trace 
 
+2 Mild 
 
+3 Moderate 
 
+4 Severe 
 
Not evaluable 
Please indicate the total regurgitation severity: 
 
0 None 
 
+1 Trivial/Trace 

 
EDWARDS 
          TRIAL NUMBER 2012-02 
COMMENCETM TRIAL  
7 O
 
 
Subject Study ID  
201202  
 
 
- 
 
 
 
 
    Site#  
 
 
 
 
 
ECHO CORE LAB EVALUATION 
Page 7 of 10
 
 
Study 2012‐02  
 
 
 
 
 
 
 
 
+2 Mild 
 
+3 Moderate 
 
+4 Severe 
 
Not evaluable 
Primary mechanism of mitral valve regurgitation (Note: Only applicable if subject is in the mitral arm at baseline visit) 
 
Type I – Normal Leaflet Motion 
 
Type II – Leaflet Prolapse 
 
Type IIIa – Restricted leaflet opening 
 
Type IIIb – Restricted leaflet closure 
 
Not evaluable 
 
Not applicable 
Valve Morphology 
Please indicate the degree of calcification: 
 
Not evaluable 
 
None 
 
Mild  
 
Moderate  
 
Heavy 
Please indicate the degree of annular calcification (only applicable to mitral arm): 
 
Not applicable 
 
Not evaluable 
 
None 
 
Mild  
 
Moderate  

 
EDWARDS 
          TRIAL NUMBER 2012-02 
COMMENCETM TRIAL  
8 O
 
 
Subject Study ID  
201202  
 
 
- 
 
 
 
 
    Site#  
 
 
 
 
 
ECHO CORE LAB EVALUATION 
Page 8 of 10
 
 
Study 2012‐02  
 
 
 
 
 
 
 
 
Heavy 
Please indicate whether the following morphologies were observed: 
No 
Yes 
 
 
 
Cusp perforation 
 
 
Pannus formation 
 
 
Thrombus 
 
 
Vegetation 
 
 
Ring abscess 
 
 
Pseudoaneurysm 
 
Non‐Trial Arm Valve Assessment 
Please indicate the level of tricuspid valve regurgitation 
 
0 None 
 
+1 Trivial/Trace 
 
+2 Mild 
 
+3 Moderate 
 
+4 Severe 
 
Not evaluable 
Please indicate the level of mitral valve regurgitation 
[Note:  Select ‘Not applicable’ if subject is in the Mitral Trial arm] 
 
0 None 
 
+1 Trivial/Trace 
 
+2 Mild 
 
+3 Moderate 

 
EDWARDS 
          TRIAL NUMBER 2012-02 
COMMENCETM TRIAL  
9 O
 
 
Subject Study ID  
201202  
 
 
- 
 
 
 
 
    Site#  
 
 
 
 
 
ECHO CORE LAB EVALUATION 
Page 9 of 10
 
 
Study 2012‐02  
 
 
 
 
 
 
 
 
+4 Severe 
 
Not evaluable 
 
Not applicable 
Please indicate the level of aortic valve regurgitation 
[Note:  Select ‘Not applicable’ if subject is in the Aortic Trial arm] 
 
0 None 
 
+1 Trivial/Trace 
 
+2 Mild 
 
+3 Moderate 
 
+4 Severe 
 
Not evaluable 
 
Not applicable 
     
Pericardial effusion 
Please indicate the level of pericardial effusion: 
 
None 
 
Small 
 
Moderate 
 
Large 
 
Tamponade 
 
Not evaluable 
 
Other, specify: 
 
RV Function 
Please indicate the overall assessment of the right ventricle 

 
EDWARDS 
          TRIAL NUMBER 2012-02 
COMMENCETM TRIAL  
10 O
 
 
Subject Study ID  
201202  
 
 
- 
 
 
 
 
    Site#  
 
 
 
 
 
ECHO CORE LAB EVALUATION 
Page 10 of 10
 
 
Study 2012‐02  
 
 
 
 
 
 
 
 
Normal 
 
Abnormal 
ECHO Quality 
Please indicate the overall quality of the ECHOs 
 
Good 
 
Fair 
 
Poor 
 
Inadequate 
COMMENTS: 
 

EDWARDS LIFESCIENCES LLC 
CLINICAL INVESTIGATIONAL PLAN 
PROTOCOL NUMBER: 2012-02 
 
ATTACHMENTS 
 
CONFIDENTIAL AND PROPRIETATARY DATA: This document and the information contained herein may not be reproduced, used, or disclosed 
without written permission from Edwards Lifesciences LLC 
REVISION J: 03 MARCH 2021 
 
 
 
 
ATTACHMENT E – CORE LABORATORY PROCEDURE MANUAL 

Core Lab Manual [Protocol # 2012-02, Revision E] 
 
CONFIDENTIAL  
Page |2 
Table of Contents 
 
 
Contents 
 
1. 
Introduction and General Objectives .................................................................................................... 3 
2. 
Echo Timeline ........................................................................................................................................ 3 
3. 
Examination Protocol – Cardiac Echo-Doppler ..................................................................................... 4 
4. 
Site Echocardiographer Checklist........................................................................................................ 12 
5. 
Core Lab Echo Tracking Form .............................................................................................................. 14 
6. 
Site Data Collection/ Entry into EDC (Echo Tracking Form) ................................................................ 14 
7. 
Shipping & Contact Information ......................................................................................................... 16 
 
 
 
 
 
 
 
 
 
 

Core Lab Manual [Protocol # 2012-02, Revision E] 
 
CONFIDENTIAL  
Page |4 
3. Examination Protocol – Cardiac Echo-Doppler 
 
OBJECTIVES: 
 
The primary objective of the initial echo-Doppler examination is to establish baseline cardiac 
anatomy and function with an emphasis on the aortic valve, aortic root and left ventricular 
size and function 
 
The primary goals of the follow-up post-implantation studies are to reassess the aortic valve 
prosthesis (structure and function) and to determine the impact of the implantation on the 
parameters evaluated. 
 
Complete Echo-Doppler examinations are required at the time points specified in the table 
above. 
 
Two-dimensional ultrasound imaging systems with pulsed, continuous wave and color 
Doppler capability, and permanent recording capabilities are required. 
 
The only accepted storage format is DICOM standard digital. 
 
You should have transducers with both fundamental and harmonic capability with frequency 
ranges that are suitable for most adult subjects (approximately 2 to 7 mHz). 
 
 
EXAMINATION PREPARATION, POSITIONING, AND GENERAL PROCEDURES: 
 
A qualified physician or sonographer must perform all ultrasound exams. If possible, 
participating sites should attempt to utilize the same person as well as the same machine for 
image acquisition throughout the trial. 
 
Prior to starting the study, the physician/sonographer should provide the subject with an 
overview of the study (duration, general procedure etc). 
 
Subjects will typically be studied while they are in the left lateral decubitus position although 
occasionally the best images will be obtained with the subject supine. 
 
EKG leads will be applied and the EKG control setting of the machine optimized to ensure a 
high quality EKG with adequate amplitude QRS complex for reliable digital capture (lead II 
equivalent preferred). 
 
All views will be acquired with 2 captures OF EACH VIEW as follows: 
o Sinus rhythm (up to 90 bpm): 3 beat capture 
o Sinus rhythm (more than 90 bpm): 5 beat capture 
o Frequent atrial or ventricular ectopy: 3 second capture 
o Atrial fibrillation or flutter, paced rhythm: 5 second capture 
 
It is essential that the view be optimized and stabilized before recording. Images are typically 
acquired during quiet respiration. Breath-holding during recording is not required unless 
necessary to ensure a stable high quality image. 
 
The spatial resolution of the images should be optimized using the highest frequencies 
capable of providing adequate penetration. For each view, the gain, compression and focus 
should be optimized so that the best echocardiographic image of the endocardial borders is 
obtained. 
 
Use echo contrast if available for images with suboptimal endocardial definition 

Core Lab Manual [Protocol # 2012-02, Revision E] 
 
CONFIDENTIAL  
Page |5 
 
The sweep speed for all spectral Doppler and M-mode recordings should be 100 mm/sec. 
NOTE: at least 3 consecutive sinus beats and at least 5 consecutive “irregular rhythm” beats 
must be captured, so adjust the number of captures accordingly. 
 
As defined in the ASE Guidelines for the Quantification of Native Valve Regurgitation, Nyquist 
settings for color Doppler assessment of the cardiac valves should be 50-60 cm/sec. 
 
We encourage you to perform measurements as needed for clinical feedback to treating 
physicians. If you do perform on-line measurements, please do not obscure the flow profiles 
of subsequent beats. We suggest storing BOTH measured and unmeasured Doppler spectra 
and images. 
 
 
Once the data storage/file save operation is complete, transmit the data to the Core Lab, 
utilizing the instruction documentation provided in the AG Mednet Desktop Agent. 
o De-identify the images through the AG Mednet while uploading data. Enter the subject 
information as specified on the Echo Tracking Form. Importantly, the height and weight 
will have to be entered at every follow-up interval. Please measure and note the blood 
pressure on the subject ID screen or as an annotation on one or more images. 
  
 
 
EXAMINATION SEQUENCE: 
 
I.  Parasternal Long Axis of LV, LVOT and AV 
 2D (Image A below) 
 Color Doppler of MR 
 Color Doppler of LVOT and aortic valve (AV) for aortic insufficiency 
 Magnified views of LVOT and aortic valve – to identify the true LVOT dimension, AV annulus 
and stent diameter (Image B below) 
 High parasternal view to see ascending aorta 
 Off-axis views to search for aortic paravalvular leak 
 Obtain an RV inflow view 
 Color flow Doppler of triscuspid valve 
 Pulse wave Doppler of inflow 1-2cm below the valve 
 Continuous wave Doppler of TV 
 
 Obtain RV outflow to include bifurcation if possible 
 Color flow Doppler of PA 
 Pulse wave Doppler of the pulmonary valve 1-2 cm below the valve in the outflow tract 
 Continuous wave Doppler of PA 
 

Core Lab Manual [Protocol # 2012-02, Revision E] 
 
CONFIDENTIAL  
Page |6 
 
A. 
 
 
 
 
           B. 
 
 
II. Parasternal Short axis at LV level 
 2D should be obtained at 3 levels: apex, mid-papillary muscle and base 
 Color Doppler of MR from the basal view is also requested 
 
III. Parasternal Short axis at aortic valve level 
 2D 
 Color Doppler of aortic valve including sewing ring of prosthesis to search for paravalvular leak 
 Color Doppler of TR is optional in this view 
 
 
 
IV. Apical 4 chamber 
 2D optimizing LV endocardial borders:  Need to see all aspects of the lateral wall, septum, and 
apex 
 Show a loop with decreased depth such that LV occupies most of the imaging sector ensuring 
all walls are visualized 
 Color Doppler of MR showing entire left atrium (to allow jet dimension/LA measurement) 
 If there is more than mild MR, provide components for PISA calculation  
o CW of MR jet 
o Zoomed PISA display (baseline shift down to optimize hemispherical PISA shell) 
o  The aliasing velocity of color scale should be shifted down or towards MR jet to around 
40cm/sec 

Core Lab Manual [Protocol # 2012-02, Revision E] 
 
CONFIDENTIAL  
Page |7 
o If possible, provide split screen (color suppress) images (i.e. one side with color, one without) 
 Color Doppler of TR with CW 
 
 
 
V. Apical 5 chamber view  
 Pulse wave Doppler of LVOT (to avoid the region of flow acceleration - sample volume should 
be positioned at valve level and then moved apically until valve noise or “clicks” are no 
longer detected and then recorded for the baseline study) 
 For post-implantation studies, it is imperative that the sample volume be placed proximal to 
the valve frame AND at a second position within the valve frame but proximal to the valve 
cusps. Studies in which there are no clips with the sample volume proximal to the valve 
frame will be considered INADEQUATE.  
 Note: record a full screen 2D image showing the pulse wave sample position (either as moving 
image or still frame) as well as the Pulse Wave Spectral Doppler for each position. It is very 
difficult to establish the sample volume position from the small image that is available when 
image and spectral display are provided simultaneously. 
 Color Doppler of LVOT and aortic valve for AI (use off axis views to ensure that all AI jets are 
demonstrated) 
 Continuous wave and pulse wave Doppler through the aortic valve  
 Continuous wave Doppler through the aortic valve 
 Pulse Wave Doppler the left ventricular outflow tract 
 
VI. Apical 2 chamber 
 2D optimizing LV endocardial borders: Need to see all aspects of the anterior wall, inferior wall, 
and apex 
 Show a loop with decreased depth such that LV occupies most of the imaging sector ensuring 
all walls are visualized 
 Color Doppler of MR 
 

Core Lab Manual [Protocol # 2012-02, Revision E] 
 
CONFIDENTIAL  
Page |8 
 
A. 
 
 
 
 
           B. 
* Image A shows the traditional 2 chamber while image B shows the 2 chamber with decreased depth 
 
 
VII. Apical long axis view (also known as 3 chamber view) 
 Color Doppler of MR  
 Color Doppler of LVOT and aortic valve for AI (use off axis views to ensure that all AI jets are 
demonstrated) 
 Pulse Wave Doppler just apical to the valve frame as specified in apical 5 chamber view 
 Note: record a full screen 2D image showing the  pulsed wave sample position (either as 
moving image or still frame) as well as the Pulse Wave Spectral Doppler for each position 
 Continuous Wave Doppler through the aortic valve 
 
 
 
 
 
 
 
     
 
      A. 
 
 
 
 
           B. 
                                                              
 
VIII. Right Parasternal view 
 Continuous Wave Doppler through the aortic valve (Note: this view is particularly useful if you 
notice an anteriorly-directed transaortic jet from parasternal views) 
 

Core Lab Manual [Protocol # 2012-02, Revision E] 
 
CONFIDENTIAL  
Page |9 
IX. Suprasternal Notch view 
 Pulsed Doppler of the descending thoracic aorta from the suprasternal notch should be 
obtained to assess for reversal of flow if significant (moderate or greater) aortic insufficiency 
is present (Note: sample volume is placed in the descending thoracic aorta below the take 
off of the subclavian artery). 
 Continuous wave Doppler interrogation of the transaortic valvular flow should also be 
obtained using the pedoff transducer  
 

Core Lab Manual [Protocol # 2012-02, Revision E] 
 
CONFIDENTIAL  
Page |10 
X. Specific Comments on Imaging Planes 
 
A. Parasternal long axis view is recorded with the transducer in the third or fourth intercostal 
space immediately to the left of the sternum. The transducer should be angled so that the 
aortic valve, mitral valve and left ventricle are in their long axis. 
 
IMAGING TIP 1: PARASTERNAL LONG AXIS VIEW 
It is important that the parasternal long axis view displays the true long axis of the ventricle 
with the left ventricle lying horizontally on the image. If it is impossible to obtain a single 
view which optimally displays the long axis of the aortic valve and aortic root as well as the 
long axis of the left ventricle, record 2 separate views. It is unacceptable to record an off-
axis view in which the apex “points up” on the screen. If this type of image is obtained try 
moving the transducer up 1-2 intercostal spaces or having the subject take a breath in. 
Sometimes having the subject move to a more lateral decubitus position will help as well. 
 
 
 
IMAGING TIP 2: PARASTERNAL LONG AXIS VIEW 
Measurement of the left ventricular outflow tract and aortic annulus is a key component of 
the study. In pre-device imaging, it is important to note that the largest annulus may not be 
in a plane with valve opening centered in the aorta. 
 
 
B.  Parasternal short axis view is obtained by angling the probe 90° with respect to the 
parasternal long axis of the LV. The goal of this view is to obtain information about the aortic 
valve as well as the LV. 
 
IMAGING TIP 3: PARASTERNAL SHORT AXIS VIEW 
This is an essential view post-op to completely assess aortic regurgitation. This may be the 
only view in which prosthetic valve medial or lateral aortic regurgitant jets are imaged. 
Imaging at the level of as well as just below the leaflets may allow you to better image these 
jets. 
 
 
C.  Apical four-chamber view provides considerable information including the relative sizes of the 
right and left ventricles and the regional function of the LV. The four chamber view is defined 
as a view which maximizes the LV long axis and the tricuspid and mitral annular dimensions. In 
this view, the full excursion of the mitral and tricuspid valves should be seen. The complete 
endocardial border of the LV will be traced for chamber volume assessment (method of discs) 
so all aspects including the apex should be visualized. In the apical four chamber view, color 
Doppler of mitral and tricuspid regurgitation should be recorded. The four chamber view 
should visualize the lateral, septal and apical walls. 
 
D. Apical two-chamber view should be obtained for the goal of assessment of LV size and 
function. The complete endocardial border of the LV will be traced for chamber volume 
assessment (method of discs) so all aspects including the apex should be visualized. The degree 
of MR by color Doppler will also be assessed. The two chamber view should visualize the 
anterior, inferior and apical walls. 

Core Lab Manual [Protocol # 2012-02, Revision E] 
 
CONFIDENTIAL  
Page |11 
 
 
IMAGING TIP 4: APICAL 4 and 2 CHAMBER VIEWS 
Because we will measure volumes from the apical views as an important end-point of the study, 
please try to avoid apical foreshortening. If the view appears to be foreshortened, please bring 
the transducer down one intercostal space and have the subject take a breath in (particularly for 
the apical two-chamber view). Sometimes this will bring out a better (not foreshortened) view. 
 
E. Apical 5 chamber and 3 chamber views are obtained to provide detailed information about the 
aortic valve color, spectral and continuous wave Doppler. 
 
IMAGING TIP 5: APICAL 5 and 3 CHAMBER VIEWS 
Both these views are essential in imaging post-device aortic regurgitant jets. Because we will 
be measuring jet vena contracta and jet length, a Res/Zoom view which includes imaging of the 
entire jet would be helpful. In addition, the 3Ch view may be used in the biplane Simpson’s 
calculation of LV volume when the 2Ch view is inadequate. Thus, careful attention to 
endocardial definition is important. 
 
 
 
XI. Abbreviations 
2D=Two-dimensional 
AI =Aortic Insufficiency 
AR=Aortic Regurgitation 
AV=Aortic Valve 
AVA=Aortic valve area 
BSA=Body Surface Area 
CO=Cardiac Output 
CSA=Cross sectional area 
ED=End diastole 
EF=Ejection fraction 
ES=End systole 
HR =Heart rate 
LA=Left atrium 
LV=Left Ventricle 
LVED=Left ventricular end diastolic volume 
LVEF=Left ventricular ejection fraction 
LVES=Left ventricular end systolic volume 
LVOT=Left ventricular outflow tract 
MR=Mitral Regurgitation 
MV=Mitral Valve 
PI=Performance Index 
PW=Pulse wave 
SV=Stroke Volume 
TR=Tricuspid Regurgitation 
TVI or VTI=Time Velocity Integral 

Core Lab Manual [Protocol # 2012-02, Revision E] 
 
CONFIDENTIAL  
Page |12 
4.  Site Echocardiographer Checklist 
 
Labeling and Demographics: 
 
Subject Study ID: __________________ 
 
Visit: 
Baseline            Operative        Discharge 
POD 105        
 
POD 390 
2 yr       
3yr 
4yr     
 5yr 
 
6 yr 
7 yr 
8 yr 
9 yr 
10 yr                
 
 
 Interim (Specify Reason): ___________________________________ 
 
Exam Date __ __/__ __ __/__ __   (Day/Month/Year) 
Height: __________ cm 
Weight: __________ kg 
Heart Rate: _______ bpm 
Rhythm: _________ 
Blood Pressure (mmHg): 
Systolic________________ 
Diastolic________________ 
 
I. Parasternal Long Axis of LV, LVOT, Aortic Valve views  
 2D 
  Color Doppler of MR 
 Color Doppler of LVOT/aortic valve for AR 
 Magnified views of LVOT and aortic valve 
 High Parasternal View (ascending aorta) 
 Off-axis views to search for paravalvular AR 
 
 
II. Parasternal Short axis at LV level 
  
LV apex, 
LV mid-papillary muscle 
LV base 
  
Color Doppler of MR (basal view—optional) 
 
 
III. Parasternal Short axis at AV level 
  
2D 
 
Color Doppler of aortic valve 
 
Color Doppler of TR (optional) 
 
 
IV. Apical 4 chamber 
 
2D optimizing LV endocardial borders 
 
LV with decreased depth 
 
Color Doppler of MR 
 
Color Doppler of TR (with CW) 
 
PISA if more than mild MR 

Core Lab Manual [Protocol # 2012-02, Revision E] 
 
CONFIDENTIAL  
Page |13 
 
V. Apical 5 chamber view 
 
Pulsed Wave Doppler of LVOT (multiple levels) 
 
Continuous wave Doppler through the AV 
 
Color Doppler of LVOT and aortic valve 
 
VI. Apical 2 chamber 
 
2D optimizing LV endocardial borders 
 
LV with decreased depth 
 
Color Doppler of MR 
 
VII. Apical long axis (3 chamber) view 
 
2 D optimizing LV endocardial borders 
  
LV with decreased depth 
 
Pulsed Wave Doppler at the LVOT 
 
Continuous Wave Doppler through AV 
 
Color Doppler of LVOT and aortic valve for AI 
 
Color Doppler of MR  
 
 
VIII. Right Parasternal view 
  
Continuous Wave Doppler through AV  
 
 
IX. Suprasternal Notch view 
  
Pulsed Wave Doppler of the descending thoracic aorta for AI 
  
Continuous Wave Doppler through AV  
 

Core Lab Manual [Protocol # 2012-02, Revision E] 
 
CONFIDENTIAL  
Page |14 
5. Core Lab Echo Tracking Form 
 
An Echo Tracking Form will be completed for each subject including the following information, 
and will be submitted along with the echo data via AG Mednet (vendor providing digital transfer 
of echo data) to the Core Lab: 
 
1.  Follow-up interval 
2.  Exam transfer date 
3.  Exam date 
4.  Subject number 
5.  Site number 
6.  Echo type: TTE/ TEE 
7.  Heart rate (bpm) 
8.  Cardiac rhythm 
9.   Site comments 
10. Name and email of person completing form 
11. Scan date 
12. Date completed 
13. DICOM scan date 
14. Echo scanner manufacturer name and model 
15. Subject height (cm) and weight (kg) 
6. Site Data Collection/ Entry into Oracle EDC (Echo Tracking Form) 
Each echocardiogram should also be read by the sites and data should be entered on the 
appropriate case report form (CRF). Data to be reported in addition to what is requested in the 
Echo Tracking Form include the following measurements: 
 
 Subject blood pressure (systolic and diastolic) 
 
 LVOT assessment: 
 Peak velocity 
 Peak gradient 
 Mean gradient 
 VTI 
 
 Aortic valve assessment: 
 Peak velocity 
 Peak gradient 
 Mean gradient 
 VTI 
 Annulus size (cm) 
 AV area (cm2) 
 
 Aortic regurgitation severity 
 0 None 
 +1 Trivial/Trace 

Core Lab Manual [Protocol # 2012-02, Revision E] 
 
CONFIDENTIAL  
Page |15 
 +2 Mild 
 +3 Moderate  
 +4 Severe 
 Indeterminate 
 
 Mitral regurgitation severity 
 0 None 
 +1 Trivial/Trace 
 +2 Mild 
 +3 Moderate  
 +4 Severe 
 Indeterminate 
 
 LVEF 
 Range of LVEF 
 Method used to determine LVEF (single plane or biplane) 
 
 Severity of paravalvular leak (PVL) 
 0 None 
 +1 Trivial/Trace 
 +2 Mild 
 +3 Moderate  
 +4 Severe 
 Indeterminate 
 
 Assessment of RV function 
 Normal 
 Mildly reduced 
 Severely reduced 
 Indeterminate 
 
 Method of delivery of echocardiographs to Core Lab  
 Images uploaded, FedEx, UPS, DHL, Other  
 Tracking number 
 
 
 
 
 
 
 
 
 
 
 

Core Lab Manual [Protocol # 2012-02, Revision E] 
 
CONFIDENTIAL  
Page |16 
7.  Shipping & Contact Information 
 
A copy of all documents and data must be kept at your site. Documents and CD’s must be 
labeled with the trial protocol number (Protocol # 2012-02), the site ID, subject ID, subject 
initials, exam date, and exam interval. 
 
Though all data is preferred to be uploaded digitally via AG Mednet, if shipping CDs, please send 
us an e-mail at
 when you ship your package. Upon its receipt, an 
official e-mail notification will be sent from the Core Lab to your site coordinator. Please confirm 
that the e-mail notification correlates with your shipping records. You should contact the Core 
Lab immediately with any discrepancies or if you have shipped a study but you have not 
received an e-mail notification within 2 business days. 
 
Please do not hesitate to contact us with any questions. For non-urgent communications, e-mail 
is typically the best means. 
 
For echo-related urgent questions, please call 
  
 
 are looking forward to being your partners in this important clinical trial. 
 

Core Lab Manual [Protocol # 2012-02, Revision F] 
 
CONFIDENTIAL  
Page | 2 
 
Table of Contents 
 
 
Contents 
 
1. 
Introduction and General Objectives ................................................................................................ 3 
2. 
Echo Timeline .................................................................................................................................. 3 
3. 
Examination Protocol – Cardiac Echo-Doppler ................................................................................. 4 
4. 
Site Echocardiographer Checklist ................................................................................................... 11 
5. 
Core Lab Echo Tracking Form ......................................................................................................... 13 
6. 
Site Data Collection/ Entry into EDC (Echo Tracking Form) ............................................................. 13 
7. 
Shipping & Contact Information ..................................................................................................... 15 
 
 
 
 
 
 
 
 

Core Lab Manual [Protocol # 2012-02, Revision F] 
 
CONFIDENTIAL  
Page | 4 
 
If applicable, always label the echo (or CD) with Subject ID, Visit Interval, and Exam Date and 
attach the Echo (Site) worksheet with vitals/ heart rhythm information. Please check to see that 
the demographic information on the images matches the data sheet. 
 
3. Examination Protocol – Cardiac Echo-Doppler 
 
OBJECTIVES: 
 
The primary objective of the initial echo-Doppler examination is to establish baseline cardiac 
anatomy and function with an emphasis on the mitral valve and left ventricular size and 
function 
 
The primary goals of the follow-up post-implantation studies are to reassess the mitral valve 
prosthesis (structure and function) and to determine the impact of the implant on the 
parameters evaluated. 
 
Complete Echo-Doppler examinations are required at the time points specified in the table 
above. 
 
Two-dimensional ultrasound imaging systems with pulsed, continuous wave and color 
Doppler capability, and permanent recording capabilities are required. 
 
The only accepted storage format is DICOM standard digital. 
 
You should have transducers with both fundamental and harmonic capability with 
frequency ranges that are suitable for most adult subjects (approximately 2 to 7 mHz). 
 
 
EXAMINATION PREPARATION, POSITIONING, AND GENERAL PROCEDURES: 
 
A qualified physician or sonographer must perform all ultrasound exams. If possible, 
participating sites should attempt to utilize the same person as well as the same machine 
for image acquisition throughout the trial. 
 
Prior to starting the study, the physician/sonographer should provide the subject with an 
overview of the study (duration, general procedure etc). 
 
Subjects will typically be studied while they are in the left lateral decubitus position 
although occasionally the best images will be obtained with the subject supine. 
 
EKG leads will be applied and the EKG control setting of the machine optimized to ensure a 
high quality EKG with adequate amplitude QRS complex for reliable digital capture (lead II 
equivalent preferred). 
 
All views will be acquired with 2 captures OF EACH VIEW as follows: 
o Sinus rhythm (up to 90 bpm): 3 beat capture 
o Sinus rhythm (greater than 90 bpm): 5 beat capture 
o Frequent atrial or ventricular ectopy: 3 second capture 
o Atrial fibrillation or flutter, paced rhythm: 5 second capture 
 
It is essential that the view be optimized and stabilized before recording. Images are 
typically acquired during quiet respiration. Breath-holding during recording is not required 
unless necessary to ensure a stable high quality image. 

Core Lab Manual [Protocol # 2012-02, Revision F] 
 
CONFIDENTIAL  
Page | 5 
 
 
The spatial resolution of the images should be optimized using the highest frequencies 
capable of providing adequate penetration. For each view, the gain, compression and focus 
should be optimized so that the best echocardiographic image of the endocardial borders is 
obtained. 
 
Use echo contrast if available for images with suboptimal endocardial definition 
 
The sweep speed for all spectral Doppler and M-mode recordings should be 100 mm/sec. 
NOTE: at least 3 consecutive sinus beats and at least 5 consecutive “irregular rhythm” beats 
must be captured, so adjust the number of captures accordingly. 
 
As defined in the ASE Guidelines for the Quantification of Native Valve Regurgitation, 
Nyquist settings for color Doppler assessment of the cardiac valves should be 50-60 cm/sec. 
 
We encourage you to perform measurements as needed for clinical feedback to treating 
physicians. If you do perform on-line measurements, please do not obscure the flow profiles 
of subsequent beats. We suggest storing BOTH measured and unmeasured Doppler spectra 
and images. 
 
 
Once the data storage/file save operation is complete, transmit the data to the Core Lab, 
utilizing the instruction documentation provided in the AG Mednet Desktop Agent. 
o De-identify the images through the AG Mednet while uploading data. Enter the subject 
information as specified on the Echo Tracking Form. Importantly, the height and weight 
will have to be entered at every follow-up interval. Please measure and note the blood 
pressure on the subject ID screen or as an annotation on one or more images. 
  
 
 
EXAMINATION SEQUENCE: 
 
I.  Parasternal Long Axis of LV, LVOT, and MV 
 2D (Image A below) 
 Color Doppler of Aortic valve 
 Color Doppler of Mitral Valve for mitral regurgitation 
 Magnified views of LVOT and aortic valve – to identify the true LVOT dimension 
 Magnify Mitral valve  
 Obtain an RV inflow view 
 

Core Lab Manual [Protocol # 2012-02, Revision F] 
 
CONFIDENTIAL  
Page | 6 
 
 
A. 
 
 
 
 
           B. 
 
 
 
 
II. Parasternal Short axis at LV level 
 
2d should be obtained at 4 levels: apex, mid-papillary muscle, mitral valve, and LV outflow 
tract   
 
Color Doppler the Mitral valve for regurgitation at the mitral valve and LVOT level views. 
 
III. Parasternal Short axis at aortic valve level 
 2D 
 Zoom image of Aortic Valve 
 Color Doppler of aortic valve   
 Color Doppler of tricuspid valve 
 
 
 
IV. Apical 4 chamber 
 2D optimizing LV endocardial borders:  Need to see all aspects of the lateral wall, septum, 
and apex 
 Zoom image of Mitral valve  
 Show a loop with decreased depth such that LV occupies most of the imaging sector ensuring 
all walls are visualized 
 Color Doppler of MR showing entire left atrium (to allow jet dimension/LA measurement) 

Core Lab Manual [Protocol # 2012-02, Revision F] 
 
CONFIDENTIAL  
Page | 7 
 
 Provide components for PISA calculation  
o CW of MR jet 
o PW of MR jet 
o Zoomed PISA display (baseline shift down to optimize hemispherical PISA shell) 
o  The aliasing velocity of color scale should be shifted down or towards MR jet to around 
40cm/sec 
o If possible, provide split screen (color suppress) images (i.e. one side with color, one 
without) 
o Pulse wave Doppler the mitral valve inflow. Maximize spectral Doppler wave form to 
provide a large enough tracing to make calculations. 
o Continuous wave Doppler the mitral valve inflow. Maximize spectral Doppler wave form to 
provide a large enough tracing to make calculations. 
  Color flow Doppler of tricuspid valve 
 Continuous wave Doppler of TV 
 
 
 
V. Apical 5 chamber view  
 2D image of apical 5 chamber 
 Pulse wave Doppler of LVOT (to avoid the region of flow acceleration - sample volume 
should be positioned at valve level and then moved apically until valve noise or “clicks” are 
no longer detected and then recorded for the baseline study)  
 Continuous wave Doppler through the aortic valve 
 Note: record a full screen 2D image showing the pulse wave sample position (either as 
moving image or still frame) as well as the Pulse Wave Spectral Doppler for each position. It is 
very difficult to establish the sample volume position from the small image that is available 
when image and spectral display are provided simultaneously. 
 
VI. Apical 2 chamber 
 2D optimizing LV endocardial borders: Need to see all aspects of the anterior wall, inferior 
wall, and apex 
 Zoom image of Mitral valve 
 Show a loop with decreased depth such that LV occupies most of the imaging sector ensuring 
all walls are visualized 
 Color Doppler of MR 

Core Lab Manual [Protocol # 2012-02, Revision F] 
 
CONFIDENTIAL  
Page | 8 
 
 
 
A. 
 
 
 
 
           B. 
* Image A shows the traditional 2 chamber while image B shows the 2 chamber with decreased depth 
 
 
VII. Apical long axis view (also known as 3 chamber view) 
 2D image of apical long axis 
 Color Doppler of Mitral valve  
 Zoom image of mitral valve 
 Pulse Wave Doppler just apical to the valve frame as specified in apical 5 chamber view 
 Note: record a full screen 2D image showing the  pulsed wave sample position (either as 
moving image or still frame) as well as the Pulse Wave Spectral Doppler for each position 
 Continuous Wave Doppler through the aortic valve 
 
 
 
 
 
     
 
      A. 
 
 
 
 
           B. 
                                                              
 
VIII. Non imaging transducer in apical window 
 Continuous wave Doppler interrogation of the mitral valvular flow should also be obtained 
using the pedoff transducer 

Core Lab Manual [Protocol # 2012-02, Revision F] 
 
CONFIDENTIAL  
Page | 9 
 
IX. Specific Comments on Imaging Planes 
 
A. Parasternal long axis view is recorded with the transducer in the third or fourth intercostal 
space immediately to the left of the sternum. The transducer should be angled so that the 
aortic valve, mitral valve and left ventricle are in their long axis. 
 
IMAGING TIP 1: PARASTERNAL LONG AXIS VIEW 
It is important that the parasternal long axis view displays the true long axis of the ventricle 
with the left ventricle lying horizontally on the image. If it is impossible to obtain a single 
view which optimally displays the long axis of the aortic valve, mitral valve, and aortic root 
as well as the long axis of the left ventricle, record 2 separate views. It is unacceptable to 
record an off-axis view in which the apex “points up” on the screen. If this type of image is 
obtained try moving the transducer up 1-2 intercostal spaces or having the subject take a 
breath in. Sometimes having the subject move to a more lateral decubitus position will 
help as well. 
 
 
 
IMAGING TIP 2: PARASTERNAL LONG AXIS VIEW 
Measurement of the left ventricular outflow tract and aortic valve and mitral valve are the 
key components of the study.  
 
 
B.  Parasternal short axis view is obtained by angling the probe 90° with respect to the 
parasternal long axis of the LV. The goal of this view is to obtain information about the aortic 
valve, the mitral valve as well as the LV. 
 
IMAGING TIP 3: PARASTERNAL SHORT AXIS VIEW 
This is an essential view post-op to completely assess mitral regurgitation. This may be the 
only view in which prosthetic valve regurgitant jets are imaged. Imaging at the level of as 
well as just below the leaflets may allow you to better image these jets. 
 
 
C.  Apical four-chamber view provides considerable information including the relative sizes of 
the right and left ventricles and the regional function of the LV. The four chamber view is 
defined as a view which maximizes the LV long axis and the tricuspid and mitral annular 
dimensions. In this view, the full excursion of the mitral and tricuspid valves should be seen. 
The complete endocardial border of the LV will be traced for chamber volume assessment 
(method of discs) so all aspects including the apex should be visualized. In the apical four 
chamber view, color Doppler of mitral and tricuspid regurgitation should be recorded. The 
four chamber view should visualize the lateral, septal and apical walls. 
 
D. Apical two-chamber view should be obtained for the goal of assessment of LV size and 
function. The complete endocardial border of the LV will be traced for chamber volume 
assessment (method of discs) so all aspects including the apex should be visualized. The 
degree of MR by color Doppler will also be assessed. The two chamber view should visualize 
the anterior, inferior and apical walls. 
 

Core Lab Manual [Protocol # 2012-02, Revision F] 
 
CONFIDENTIAL  
Page | 10 
 
 
IMAGING TIP 4: APICAL 4 and 2 CHAMBER VIEWS 
Because we will measure volumes from the apical views as an important end-point of the 
study, please try to avoid apical foreshortening. If the view appears to be foreshortened, please 
bring the transducer down one intercostal space and have the subject take a breath in 
(particularly for the apical two-chamber view). Sometimes this will bring out a better (not 
foreshortened) view. 
 
E. Apical 5 chamber and 3 chamber views are obtained to provide detailed information about 
the aortic valve and mitral valve color, and the spectral and continuous wave Doppler. 
 
IMAGING TIP 5: APICAL 5 and 3 CHAMBER VIEWS 
Both these views are essential in imaging post-device mitral regurgitant jets. Because we will 
be measuring jet vena contracta and jet length, a Res/Zoom view which includes imaging of 
the entire jet would be helpful. In addition, the 3Ch view may be used in the biplane 
Simpson’s calculation of LV volume when the 2Ch view is inadequate. Thus, careful attention 
to endocardial definition is important. 
 
 
XI. Abbreviations 
2D=Two-dimensional 
AI =Aortic Insufficiency 
AR=Aortic Regurgitation 
AV=Aortic Valve 
AVA=Aortic valve area 
BSA=Body Surface Area 
CO=Cardiac Output 
CSA=Cross sectional area 
ED=End diastole 
EF=Ejection fraction 
ES=End systole 
HR =Heart rate 
LA=Left atrium 
LV=Left Ventricle 
LVED=Left ventricular end diastolic volume 
LVEF=Left ventricular ejection fraction 
LVES=Left ventricular end systolic volume 
LVOT=Left ventricular outflow tract 
MR=Mitral Regurgitation 
MV=Mitral Valve 
PI=Performance Index 
PW=Pulse wave 
SV=Stroke Volume 
TR=Tricuspid Regurgitation 
TVI or VTI=Time Velocity Integral 

Core Lab Manual [Protocol # 2012-02, Revision F] 
 
CONFIDENTIAL  
Page | 11 
 
4. Site Echocardiographer Checklist 
 
Labeling and Demographics: 
 
Subject Study ID: __________________ 
 
Visit: 
Baseline            Operative        Discharge 
POD 105        
 
POD 390 
2 yr       
3yr 
4yr     
 5yr 
 
6 yr 
7 yr 
8 yr 
9 yr 
10 yr                
 
 
 Interim (Specify Reason): ___________________________________ 
 
Exam Date __ __/__ __ __/__ __   (Day/Month/Year) 
Height: __________ cm 
Weight: __________ kg 
Heart Rate: _______ bpm 
Rhythm: _________ 
Blood Pressure (mmHg): 
Systolic________________ 
Diastolic________________ 
 
I. Parasternal Long Axis of LV, LVOT, MV views  
 2D 
  Color Doppler of Mitral Valve for MR 
 Magnified views of LVOT and aortic valve 
    Magnified view of Mitral valve 
  
II. Parasternal Short axis at LV level 
  
LV apex, 
LV mid-papillary muscle 
LV Mitral valve 
LVOT 
Color Doppler of the Mitral valve for regurgitation at the mitral valve and LVOT level 
 
III. Parasternal Short axis at AV level 
  
2D 
 
Color Doppler of TR (optional) 
 
 
IV. Apical 4 chamber 
 
2D optimizing LV endocardial borders 
 
LV with decreased depth 
          Zoom Mitral valve 
 
Color Doppler of Mitral valve 
 
Color Doppler of TR (with CW) 
 
PISA  information for mitral valve 
 
 
 

Core Lab Manual [Protocol # 2012-02, Revision F] 
 
CONFIDENTIAL  
Page | 12 
 
 
V. Apical 5 chamber view 
 
Pulsed Wave Doppler of LVOT (multiple levels) 
 
Continuous wave Doppler through the AV 
 
 
 
VI. Apical 2 chamber 
 
2D optimizing LV endocardial borders 
LV with decreased depth 
         Zoom Mitral valve 
 
Color Doppler of Mitral valve 
 
VII. Apical long axis (3 chamber) view 
 
2 D optimizing LV endocardial borders 
  
LV with decreased depth 
          Zoom Mitral valve 
 
Pulsed Wave Doppler at the LVOT 
 
Continuous Wave Doppler through AV 
 
Color Doppler of Mitral valve for MR  
 
VIII. Non imaging transducer in apical window 
Continuous wave Doppler interrogation of the Mitral valvular flow should also be 
obtained using the pedoff transducer 
 
 

Core Lab Manual [Protocol # 2012-02, Revision F] 
 
CONFIDENTIAL  
Page | 13 
 
5. Core Lab Echo Tracking Form 
 
An Echo Tracking Form will be completed for each subject including the following information, 
and will be submitted along with the echo data via AG Mednet (vendor providing digital 
transfer of echo data) to the Core Lab: 
 
1.  Follow-up interval 
2.  Exam transfer date 
3.  Exam date 
4.  Subject number 
5.  Site number 
6.  Echo type: TTE/ TEE 
7.  Heart rate (bpm) 
8.  Cardiac rhythm 
9.   Site comments 
10. Name and email of person completing form 
11. Scan date 
12. Date completed 
13. DICOM scan date 
14. Echo scanner manufacturer name and model 
15. Subject height (cm) and weight (kg) 
6. Site Data Collection/ Entry into Oracle EDC (Echo Tracking Form) 
Each echocardiogram should also be read by the sites and data should be entered on the 
appropriate case report form (CRF). Data to be reported in addition to what is requested in 
the Echo Tracking Form include the following measurements: 
 
 Subject blood pressure (systolic and diastolic) 
 
 LVOT assessment: 
 Peak velocity 
 Peak gradient 
 Mean gradient 
 VTI 
 
 Mitral valve assessment: 
 Peak velocity 
 Peak gradient 
 Mean gradient 
 VTI 
 Annulus size (cm) 
 MV area (cm2) 
 
 Mitral regurgitation severity (Paravalvular, Transvalvular and Total 
Insufficiency/Regurgitation) 

Core Lab Manual [Protocol # 2012-02, Revision F] 
 
CONFIDENTIAL  
Page | 14 
 
 0 None 
 +1 Trivial/Trace 
 +2 Mild 
 +3 Moderate  
 +4 Severe 
 Indeterminate 
 
 Non-study valve regurgitation severity 
 0 None 
 +1 Trivial/Trace 
 +2 Mild 
 +3 Moderate  
 +4 Severe 
 Indeterminate 
 
 LVEF 
 Range of LVEF 
 Method used to determine LVEF (single plane or biplane) 
 
 
 Assessment of RV function 
 Normal 
 Mildly reduced 
 Severely reduced 
 Indeterminate 
 
 Method of delivery of echocardiographs to Core Lab  
 Images uploaded, FedEx, UPS, DHL, Other  
 Tracking number 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Core Lab Manual [Protocol # 2012-02, Revision F] 
 
CONFIDENTIAL  
Page | 15 
 
7. Shipping & Contact Information 
 
A copy of all documents and data must be kept at your site. Documents and CD’s must be 
labeled with the trial protocol number (Protocol # 2012-02), the site ID, subject ID, subject 
initials, exam date, and exam interval. 
 
Though all data is preferred to be uploaded digitally via AG Mednet, if shipping CDs, please 
send us an e-mail at 
 when you ship your package. Upon its receipt, 
an official e-mail notification will be sent from the Core Lab to your site coordinator. Please 
confirm that the e-mail notification correlates with your shipping records. You should contact 
the Core Lab immediately with any discrepancies or if you have shipped a study but you have 
not received an e-mail notification within 2 business days. 
 
Please do not hesitate to contact us with any questions. For non-urgent communications, e-
mail is typically the best means. 
 
For echo-related urgent questions, please call 
  
 
We are looking forward to being your partners in this important clinical trial. 
 

EDWARDS LIFESCIENCES LLC 
CLINICAL INVESTIGATIONAL PLAN 
PROTOCOL NUMBER: 2012-02 
 
ATTACHMENTS 
 
CONFIDENTIAL AND PROPRIETATARY DATA: This document and the information contained herein may not be reproduced, used, or disclosed 
without written permission from Edwards Lifesciences LLC 
REVISION J: 03 MARCH 2021 
 
 
 
          ATTACHMENT F – SERUM GLYCEROL SAMPLE COLLECTION 
MANUAL  
 
No Longer In Use 
 
 
 
 

EDWARDS LIFESCIENCES LLC 
 
ATTACHMENTS 
CLINICAL INVESTIGATIONAL PLAN 
PROTOCOL NUMBER: 2012-02 
CONFIDENTIAL AND PROPRIETATARY DATA: THIS DOCUMENT AND THE INFORMATION CONTAINED HEREIN MAY NOT BE REPRODUCED, USED, OR DISCLOSED 
WITHOUT WRITTEN PERMISSION FROM EDWARDS LIFESCIENCES LLC 
REVISION J: 03 MARCH 2021 
 
 
 
 
ATTACHMENT G – QUALITY OF LIFE QUESTIONNAIRE 
(SF-12 V2) 
 
 
 
 
 
 
 
 
 
 
 
No Longer In Use 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

EDWARDS LIFESCIENCES LLC 
 
ATTACHMENTS 
CLINICAL INVESTIGATIONAL PLAN 
PROTOCOL NUMBER: 2012-02 
CONFIDENTIAL AND PROPRIETATARY DATA: THIS DOCUMENT AND THE INFORMATION CONTAINED HEREIN MAY NOT BE REPRODUCED, USED, OR DISCLOSED 
WITHOUT WRITTEN PERMISSION FROM EDWARDS LIFESCIENCES LLC 
REVISION J: 03 MARCH 2021 
 
 
 
 
 
 
 
 
 
 
 
ATTACHMENT H – ADVERSE EFFECT (CODES & DEFINITIONS) 
 

EDWARDS LIFESCIENCES LLC 
CLINICAL INVESTIGATIONAL PLAN 
PROTOCOL NUMBER: 2012-02 
 
ATTACHMENTS 
 
CONFIDENTIAL AND PROPRIETATARY DATA: This document and the information contained herein may not be reproduced, used, or disclosed 
without written permission from Edwards Lifesciences LLC 
REVISION J: 03 MARCH 2021 
 
 
 
ATTACHMENT J – RESPONSIBILITIES 
INVESTIGATOR & SPONSOR 

INVESTIGATORS’ RESPONSIBILITIES 
1.0 
Investigators' Responsibilities For Significant Risk Device Investigations (Nov. 1995) 
This document is intended to assist investigators in identifying and complying with their responsibilities in 
connection with the conduct of clinical investigations involving medical devices. Although this guidance 
primarily addresses duties imposed upon clinical investigators by regulations of the Food and Drug 
Administration (FDA), investigators should be cognizant of additional responsibilities that may derive from 
other sources (such as the study protocol itself, the investigator agreement, any conditions of approval 
imposed by FDA or the governing Institutional Review Board, as well as institutional policy and state law). 
2.0 
General Responsibilities of Investigators (21 CFR 812.100) 
• 
Ensuring that the investigation is conducted according to the signed agreement, the 
investigational plan and applicable FDA regulations.  
• 
Protecting the rights, safety, and welfare of subjects under the investigator's care.  
• 
Controlling devices under investigation.  
• 
Ensuring that informed consent is obtained from each subject in accordance with 21 CFR Part 50, 
and that the study is not commenced until FDA and IRB approvals have been obtained.  
3.0 
Specific Responsibilities of Investigators (21 CFR 812.110) 
• 
Awaiting IRB approval and any necessary FDA approval before requesting written informed 
consent or permitting subject participation.  
• 
Conducting the investigation in accordance with:  
o 
the signed agreement with the sponsor  
o 
the investigational plan  
o 
the regulations set forth in 21 CFR Part 812 and all other applicable FDA regulations  
o 
any conditions of approval imposed by an IRB or FDA  
• 
Supervising the use of the investigational device. An investigator shall permit an investigational 
device to be used only with subjects under the investigator's supervision. An investigator shall not 
supply an investigational device to any person not authorized under 21 CFR Part 812 to receive 
it.  
• 
Disposing of the device properly. Upon completion or termination of a clinical investigation or the 
investigator's part of an investigation, or at the sponsor's request, an investigator shall return to 
the sponsor any remaining supply of the device or otherwise dispose of the device as the sponsor 
directs.  
4.0 
Maintaining Records (21 CFR 812.140) 
An investigator shall maintain the following accurate, complete, and current records relating to the 
investigator's participation in an investigation: 
• 
Correspondence with another investigator, an IRB, the sponsor, a monitor, or FDA.  
• 
Records of receipt, use or disposition of a device that relate to:  
o 
the type and quantity of the device, dates of receipt, and batch numbers or code marks  
o 
names of all persons who received, used, or disposed of each device  
o 
the number of units of the device returned to the sponsor, repaired, or otherwise 
disposed of, and the reason(s) therefore  
• 
Records of each subject's case history and exposure to the device, including:  
o 
documents evidencing informed consent and, for any use of a device by the investigator 
without informed consent, any written concurrence of a licensed physician and a brief 
description of the circumstances justifying the failure to obtain informed consent  
o 
all relevant observations, including records concerning adverse device effects (whether 
anticipated or not), information and data on the condition of each subject upon entering, 
and during the course of, the investigation, including information about relevant previous 
medical history and the results of all diagnostic tests  
o 
a record of the exposure of each subject to the investigational device, including the date 
and time of each use, and any other therapy  
• 
The protocol, with documents showing the dates of and reasons for each deviation from the 
protocol.  

INVESTIGATORS’ RESPONSIBILITIES 
• 
Any other records that FDA requires to be maintained by regulation or by specific requirement for 
a category of investigations or a particular investigation.  
5.0 
Inspections (21 CFR 812.145) 
Investigators are required to permit FDA to inspect and copy any records pertaining to the investigation 
including, in certain situations, those which identify subjects. 
6.0 
Submitting Reports (21 CFR 812.150) 
An investigator shall prepare and submit the following complete, accurate, and timely reports: 
• 
To the sponsor and the IRB:  
o 
Any unanticipated adverse device effect occurring during an investigation. (Due no later 
than 10 working days after the investigator first learns of the effect.)  
o 
Progress reports on the investigation. (These reports must be provided at regular 
intervals, but in no event less often than yearly. If there is a study monitor, a copy of the 
report should also be sent to the monitor.)  
o 
Any deviation from the investigational plan made to protect the life or physical well-being 
of a subject in an emergency. (Report is due as soon as possible but no later than 5 
working days after the emergency occurs. Except in emergency situations, a protocol 
deviation requires prior sponsor approval; and if the deviation may affect the scientific 
soundness of the plan or the rights, safety, or welfare of subjects, prior FDA and IRB 
approval are required.)  
o 
Any use of the device without obtaining informed consent. (Due within 5 working days 
after such use.)  
o 
A final report. (Due within 3 months following termination or completion of the 
investigation or the investigator's part of the investigation. For additional guidance, see 
the discussion under the section entitled "Annual Progress Reports and Final Reports.")  
o 
Any further information requested by FDA or the IRB about any aspect of the 
investigation.  
• 
To the Sponsor: Withdrawal of IRB approval of the investigator's part of an investigation. (Due 
within 5 working days of such action)  
7.0 
Investigational Device Distribution and Tracking 
The IDE regulations prohibit an investigator from providing an investigational device to any person not 
authorized to receive it [21 CFR 812.110(c)]. The best strategy for reducing the risk that an investigational 
device could be improperly dispensed (whether purposely or inadvertently) is for the sponsor and the 
investigators to closely monitor the shipping, use, and final disposal of the device(s). Upon completion or 
termination of a clinical investigation (or the investigator's part of an investigation), or at the sponsor's 
request, an investigator is required to return to the sponsor any remaining supply of the device or 
otherwise to dispose of the device as the sponsor directs [21 CFR 812.110(c)]. Investigators must also 
maintain complete, current and accurate records of the receipt, use, or disposition of investigational 
devices [21 CFR 812.140(a)(2)]. Specific recordkeeping requirements are set forth at 21 CFR 812.140(a). 
8.0 
Prohibition of Promotion and Other Practices (21 CFR 812.7) 
The IDE regulations prohibit the promotion and commercialization of a device that has not been first 
cleared or approved for marketing by FDA. This prohibition is applicable to sponsors and investigators (or 
any person acting on behalf of a sponsor or investigator), and encompasses the following activities: 
• 
Promotion or test marketing of the investigational device  
• 
Charging subjects or investigators for the device a price larger than is necessary to recover the 
costs of manufacture, research, development, and handling  
• 
Prolonging an investigation beyond the point needed to collect data required to determine 
whether the device is safe and effective  
• 
Representing that the device is safe or effective for the purposes for which it is being 
investigated. 
 

SPONSOR'S RESPONSIBILITIES 
1.0 
Sponsor's Responsibilities For Significant Risk Device Investigations (Nov. 1995) 
This document is intended to assist sponsors in identifying and complying with their responsibilities in 
connection with the conduct of clinical investigations of medical devices that are deemed "significant risk" by 
the reviewing IRB or by FDA. For a complete description of their responsibilities, sponsors should refer to the 
actual text of the regulations cited below. In addition, sponsors should be aware that a clinical investigation 
must be conducted in accordance with any requirements imposed by the reviewing IRB, by institutional 
policies, or by state law. 
2.0 
General Duties (21 CFR 812.40) 
• 
Submitting the IDE application to FDA  
• 
Obtaining both FDA and IRB approvals for the investigation and submitting certification of IRB 
approval to FDA before shipping the device to any investigator  
• 
Obtaining FDA approval and IRB approval for a supplemental application before beginning that portion 
of the investigation  
• 
Selecting qualified investigators  
• 
Ensuring proper monitoring  
• 
Ensuring patient informed consent is obtained  
3.0 
Selection of Investigators (21 CFR 812.43) 
• 
Assuring selection of investigators qualified by training and experience  
• 
Shipping the investigational device only to participating investigators  
• 
Obtaining a signed investigator's agreement containing:  
o 
investigator's curriculum vitae  
o 
statement of investigator's relevant experience, including dates  
o 
location, extent, and type of experience  
o 
if an investigator was involved in an investigation or other research that was terminated, an 
explanation of the circumstances that led to the termination  
o 
statement of the investigator's commitment to:  
 
conduct the investigation in accordance with the agreement, the investigational plan, Parts 50, 
56, and 812, and any conditions of approval imposed by the IRB or FDA  
 
supervise all testing of the device involving human subjects  
 
ensure that the requirements for informed consent are met (21 CFR Part 50)  
o 
Providing investigators with the necessary information to conduct the investigation including, but 
not necessarily limited to:  
o 
the investigational plan  
o 
the report of prior investigations  
4.0 
Monitoring (21 CFR 812.46) 
• 
Selecting monitor(s) qualified by training and experience to monitor the progress of the investigation  
• 
Securing compliance of all investigators in accordance with the signed investigator's agreement, the 
investigational plan, the requirements of this part or other applicable FDA regulations, or any condition 
of approval imposed by the reviewing IRB or FDA. If compliance cannot be secured, shipment of the 
device to the investigator and the investigator's participation in the investigation must be discontinued  
• 
Ensuring that significant new information about the investigation is provided to all reviewing IRBs, 
FDA, and investigators  
• 
Evaluating all unanticipated adverse device effects and terminating the investigation, or portions of it, if 
that effect presents an unreasonable risk to subjects (reporting requirements are listed below.)  
• 
Resuming terminated investigations only after both FDA and IRB approvals are obtained.  
5.0 
Controlling Distribution and Disposition of Devices 
Although investigators are responsible for ensuring that investigational devices are made available only to 
persons who are legally authorized to receive them (see 21 CFR 812.110(c)), sponsors also bear 
responsibility for taking proper measures to ensure that devices are not diverted outside of legally authorized 
channels. Sponsors may ship investigational devices only to qualified investigators participating in the clinical 
investigation (§ 812.43(b)). Sponsors must also maintain complete, current, and accurate records pertaining to 

SPONSOR'S RESPONSIBILITIES 
the shipment and disposition of the investigational device (§ 812.140(b)). Records of shipment shall include 
the name and address of the consignee, type and quantity of device, date of shipment, and batch number or 
code mark. Records of disposition shall describe the batch number or code marks of any devices returned to 
the sponsor, repaired, or disposed of in other ways by the investigator or another person, and the reasons for 
and method of disposal. 
To further ensure compliance with these requirements, sponsors should take appropriate measures to instruct 
investigators regarding their responsibilities with respect to recordkeeping and device disposition. The specific 
recordkeeping requirements for investigators are set forth at § 812.140(a). Upon completion or termination of a 
clinical investigation (or the investigator's part of an investigation), or at the sponsor's request, an investigator 
is required to return to the sponsor any remaining supply of the device or otherwise to dispose of the device as 
the sponsor directs (§ 812.110(c)). 
6.0 
Prohibition of Promotion and Other Practices (21 CFR 812.7) 
The IDE regulations prohibit the promotion and commercialization of a device that has not been first cleared or 
approved for marketing by FDA. This prohibition is applicable to sponsors and investigators (or any person 
acting on behalf of a sponsor or investigator), and encompasses the following activities: 
• 
Promotion or test marketing of the investigational device  
• 
Charging subjects or investigators for the device a price larger than is necessary to recover the costs 
of manufacture, research, development, and handling  
• 
Prolonging an investigation beyond the point needed to collect data required to determine whether the 
device is safe and effective  
• 
Representing that the device is safe or effective for the purposes for which it is being investigated.  
7.0 
Supplemental Applications [21 CFR 812.35(a) and (b)] 
Supplemental applications are required to be submitted to, and approved by, FDA in the following situations: 
• 
Changes in the investigational plan: FDA approval is required for any change that may affect the 
scientific soundness of the investigation or the rights, safety or welfare of the subjects. IRB approval is 
also required for changes that may affect the rights, safety or welfare of the subjects. The change in 
the investigational plan may not be implemented until FDA approval (and IRB approval, if required) is 
obtained.  
• 
Addition of new institutions: IRB approval is also required for new institutions. The investigation at 
the new institution(s) may not begin until both FDA and IRB approval(s) are obtained, and certification 
of IRB approval is submitted to FDA.  
8.0 
Maintaining Records [21 CFR 812.140(b)] 
A sponsor shall maintain the following accurate, complete, and current records relating to an investigation 
(also See Table I, next page): 
• 
Correspondence (including reports) with another sponsor, monitor, investigators, an IRB or FDA  
• 
Records of shipment, including:  
o 
name and address of consignee  
o 
type and quantity of device  
o 
date of shipment  
o 
batch numbers or code marks  
• 
Records of disposition, describing:  
o 
Batch number or code mark of devices returned, repaired, or disposed of by the investigator or 
other persons  
o 
Reasons for and method of disposal  
• 
Signed investigator agreements  
• 
Adverse device effects (whether anticipated or unanticipated) and complaints  
• 
Any other records that FDA requires by regulation or by specific requirement for a category of 
investigation or a particular investigation 

SPONSOR'S RESPONSIBILITIES 
 
Table I Responsibilities for Maintaining Records for a Significant Risk Device Study 
Records 
Maintained by Investigator 
Maintained by Sponsor 
All Correspondence Pertaining to the Investigation 
X 
X 
Shipment, Receipt, Disposition 
X 
X 
Device Administration and Use 
X 
- 
Subject Case Histories 
X 
- 
Informed Consent 
X 
- 
Protocols and Reasons for Deviations from Protocol 
X 
- 
Adverse Device Effects and Complaints 
X 
X 
Signed Investigator Agreements 
- 
X 
Membership/Employment/Conflicts of Interest 
- 
X 
Minutes of Meetings 
- 
- 
 
9.0 
Submitting Reports [21 CFR 812.150(b)] 
A sponsor shall prepare and submit the following complete, accurate, and timely reports (see Table II). 
• 
Unanticipated adverse device effects (with evaluation) to FDA, all IRBs, and investigators within 10 
working days after notification by the investigator. Subsequent reports on the effect may be required 
by FDA.  
• 
Withdrawal of IRB approval  
• 
Withdrawal of FDA approval  
• 
Current 6month investigator list  
• 
Annual progress report  see format for IDE progress report  
• 
Recall and device disposition (within 30 working days after the request was made)  
• 
Final report  see format for progress reports  
• 
Use of device without obtaining patient informed consent  
• 
Significant risk determinations by the IRB when proposed to be non-significant risk  
• 
Other reports requested by the IRB or FDA  
Table II Responsibilities for Preparing and Submitting Reports for Significant Risk Device Studies 
Type of Report 
Prepared by Investigators for 
Prepared by Sponsors for 
Unanticipated Adverse Effect Evaluation 
Sponsors & IRBs 
FDA, IRBs & Investigators 
Withdrawal of IDE Approval 
Sponsors 
FDA, IRBs, & Investigators 
Progress Report 
Sponsors, Monitors & IRBs 
FDA & IRBs 
Final Report 
Sponsors & IRBs 
FDA, IRBs, & Investigators 
Emergencies (Protocol Deviations) 
Sponsors & IRBs 
FDA 
Inability to Obtain Informed Consent 
Sponsors & IRBs 
FDA 
Withdrawal of FDA Approval 
N/A 
IRBs & Investigators 
Current Investigator List 
N/A 
FDA 
Recall and Device Disposition 
< N/A 
FDA & IRBs 
Records Maintenance Transfer 
FDA 
FDA 
Significant Risk Determinations 
N/A 
FDA 
10.0 
Inspections [21 CFR 812.145] 
Sponsors are required to permit FDA to enter and inspect (at reasonable times and in a reasonable manner) 
any establishment where devices are held (including any establishment where devices are manufactured, 
processed, packed, installed, used, or implanted or where records or results from use of devices are kept). 
FDA may also inspect and copy all records relating to an investigation including, in certain situations, records 
which, identify subjects. 

EDWARDS LIFESCIENCES LLC 
CLINICAL INVESTIGATIONAL PLAN 
PROTOCOL NUMBER: 2012-02 
 
ATTACHMENTS 
 
CONFIDENTIAL AND PROPRIETATARY DATA: This document and the information contained herein may not be reproduced, used, or disclosed 
without written permission from Edwards Lifesciences LLC 
REVISION J: 03 MARCH 2021 
 
 
 
ATTACHMENT K – SUBJECT IMPLANT CARD 

Outside of Card
Inside of Card
The following aortic valve was implanted.
MR Conditional
Non-clinical testing has demonstrated that the Edwards Aortic Bioprosthesis, Model 11000A, is MR Conditional. A patient 
with the Model 11000A valve can be scanned safely, immediately after placement of this implant under the following 
conditions:
- Static magnetic field of 1.5 tesla or 3.0 tesla.
- Maximum spatial magnetic gradient field of 2670 gauss/cm.
- Maximum MR system-reported whole body averaged specific absorption rate (SAR) of 2.0 W/kg in the normal operating 
mode for 15 minutes of scanning per sequence.
In non-clinical testing, the Edwards Aortic Bioprosthesis, Model 11000A, produced an estimated maximum in vivo
temperature rise of less than or equal to 1.8 °C at a maximum MR system reported, whole-body averaged specific 
absorption rate (SAR) of 2.0 W/kg, for 15 minutes of MR scanning in a GE Signa 64 MHz (1.5T) RF coil and a GE Signa 
HDx (3T) MR system with Software Version 15\LX\MR Software release 15.0.M4.0910.a. 
Image artifact was measured non-clinically in a GE Signa 3T HDx MR System according to ASTM F2119-07 using the spin 
echo and gradient echo sequences specified therein. The spin echo images exhibited light and dark artifacts that extended 
as far as 40 mm from the implant and partially to fully obscured the lumen. The gradient echo images exhibited opaque 
dark or light and dark triangular shaped artifacts that extended as far as 40 mm from the implant and totally obscured the 
lumen. Reduction in artifact may be possible with sequences designed for reduction of metal artifact.
Tel (USA) 800.424.3278                               Tel (outside USA) +1.949.250.2500 
IMPORTANT: For all other questions or concerns, contact:
Physician Name                                                      Contact Number                                        
Front
Back
(to have MR statement for USA)
Please affix the self-adhesive label with the serial 
number for the aortic valve implanted in this 
patient. This label may be found in the original 
device package.
Subject ID
2012-02- ________
_____________________
Trial Site Physician 
_____________________
Physician Contact #
_____________________
Hospital
Date: ____/_____/_____
Month      Day 
Year
EDWARDS Pericardial Aortic Bioprosthesis 
Model 11000A
1 Month: _____/_____     □Office visit
Month        Year            □Telephone interview
3 Month: _____/_____
Month       Year
1 year: ____/_____
Month       Year
2 year: _____/_____
Month       Year
3 year: _____/_____
Month        Year
4 year: _____/_____
Month        Year
5 year: _____/_____
Month        Year
Follow-Up Schedule

Outside of Card
Inside of Card
The following mitral valve was implanted.
MR Conditional
Non-clinical testing has demonstrated that the Edwards Pericardial Mitral Bioprosthesis, Model 11000M, is MR 
Conditional. A patient with the Model 11000M bioprosthesis can be scanned safely, immediately after placement of this 
implant under the following conditions:
- Static magnetic field of 3 tesla or less.
- Maximum Spatial gradient field of 720 gauss/cm.
- Maximum MR system-reported whole body-averaged specific absorption rate (SAR) of 3W/kg for 15 minutes of 
scanning.
In non-clinical testing, the Edwards Pericardial Mitral Bioprosthesis, Model 11000M, produced a temperature rise of less 
than or equal to 0.5 °C at a maximum MR system reported whole-body-averaged specific absorption rate (SAR) of 3W/kg 
for 15 minutes of MR scanning in a 3 tesla MR system (Excite, Software G3.0-052B, General Electric Healthcare). 
MR image quality may be compromised if the area of interest is in the same area or relatively close to the position of the 
Model 11000M bioprosthesis. Optimization of MR imaging parameters is recommended.
Tel (USA) 800.424.3278                               Tel (outside USA) +1.949.250.2500 
IMPORTANT: For all other questions or concerns, contact:
Physician Name                                                      Contact Number                                        
Front
Back
(to have MR statement for USA)
Please affix the self-adhesive label with the serial 
number for the mitral valve implanted in this 
patient. This label may be found in the original 
device package.
Subject ID
2012-02- ________
_____________________
Trial Site Physician 
_____________________
Physician Contact #
_____________________
Hospital
Date: ____/_____/_____
Month      Day 
Year
EDWARDS Pericardial Mitral Bioprosthesis Model 
11000M
1 Month: _____/_____     □Office visit
Month        Year            □Telephone interview
3 Month: _____/_____
Month       Year
1 year: ____/_____
Month       Year
2 year: _____/_____
Month       Year
3 year: _____/_____
Month        Year
4 year: _____/_____
Month        Year
5 year: _____/_____
Month        Year
Follow-Up Schedule

EDWARDS LIFESCIENCES LLC 
CLINICAL INVESTIGATIONAL PLAN 
PROTOCOL NUMBER: 2012-02 
 
ATTACHMENTS 
 
CONFIDENTIAL AND PROPRIETATARY DATA: This document and the information contained herein may not be reproduced, used, or disclosed 
without written permission from Edwards Lifesciences LLC 
REVISION J: 03 MARCH 2021 
 
 
 
ATTACHMENT L – PROTOCOL DEVIATION CODES 

Edwards Lifesciences LLC      
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Clinical Investigational Plan 
Protocol Number: 2012-02 
 
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PROTOCOL DEVIATION CODES  
SUBJECT SCREENING 
1.01 
SUBJECT DID NOT MEET INCLUSION CRITERION 
1.02 
SUBJECT MET EXCLUSION CRITERION 
1.03 
DATE OF INFORMED CONSENT IS AFTER DATE OF STUDY ENROLLMENT 
1.04 
INFORMED CONSENT WAS IMPROPERLY OBTAINED 
1.05 
PERSON OBTAINING INFORMED CONSENT DID NOT SIGN/DATE THE CONSENT FORM 
1.06 
OTHER SCREENING DEVIATION 
 
BASELINE 
2.01 
 BASELINE ECHOCARDIOGRAM NOT DONE 
2.21  
BASELINE ECHOCARDIOGRAM DONE > 60 DAYS PRIOR IMPLANT DATE 
2.03  
BASELINE BLOOD NOT DONE 
2.22  
BASELINE BLOOD DONE > 60 DAYS BEFORE IMPLANT 
2.05  
BASELINE BLOOD INCOMPLETE 
2.06  
BASELINE COAGULATION PROFILE NOT DONE 
2.23  
BASELINE COAGULATION PROFILE DONE > 60 DAYS BEFORE IMPLANT 
2.08  
BASELINE NYHA NOT DONE 
2.09  
BASELINE ELECTROCARDIOGRAM NOT DONE 
2.24  
BASELINE ELECTROCARDIOGRAM DONE > 60 DAYS BEFORE IMPLANT 
2.11  
BASELINE PHYSICAL ASSESSMENT / VITAL SIGNS NOT DONE 
2.12  
PREGNACY TEST NOT DONE 
2.13  
MEDICAL HISTORY NOT COLLECTED 
2.10 
BASELINE QUALITY OF LIFE NOT DONE 
2.14  
OTHER BASELINE DEVIATION 
 
IMPLANT SURGERY 
3.01 
 IMPLANTING SURGEON IS NOT ON APPROVED LIST 
3.02  
PROCEDURE DIAGNOSIS NOT DONE 
3.28  
INCORRECT SIZER USED 
3.04  
START SKIN INCISION TIME NOT RECORDED 
3.05  
START TIME OF ECC (PUMP) NOT RECORDED 
3.06  
START CROSS CLAMP TIME NOT RECORDED 
3.07  
START OF SIZING TIME NOT RECORDED 
3.09 
 REMOVAL CROSS CLAMP TIME NOT RECORDED 
3.10  
END ECC (PUMP) TIME NOT RECORDED 
3.11  
END SKIN CLOSURE TIME NOT RECORDED 
3.12  
UNAPPROVED CONCOMITANT PROCEDURE PERFORMED 
3.15  
VALVE SERIAL NUMBER NOT RECORDED 
3.18  
MORE THAN 2 STUDY VALVES ATTEMPTED TO BE IMPLANTED 
3.21  
START TIME FOR STUDY PROCEDURE (FIST STITCH PLACED ON THE ANNULUS) NOT RECORDED 
3.22  
TIME FIST STITCH PLACED ON THE VALVE RING NOT RECORDED 

Edwards Lifesciences LLC      
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Clinical Investigational Plan 
Protocol Number: 2012-02 
 
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3.26  
COMPLETION TIME OF STUDY PROCEDURE (LAST STITCH TIED DOWN ON THE VALVE) NOT RECORDED 
3.33  
POST-IMPLANT ECHOCARDIOGRAM NOT DONE 
3.30 
POST-IMPLANT ECHOCARDIOGRAM NOT DONE WITHIN 1 HOUR OF REMOVING THE CROSS-CLAMP 
3.31 
PRE-IMPLANT BLOOD COLLECTION (SERUM GLYCEROL) NOT DONE (ONLY REQUIRED FOR 120 SUBJECTS) 
3.19  
POST-IMPLANT BLOOD COLLECTION (SERUM GLYCEROL) NOT DONE (ONLY REQUIRED FOR 120 SUBJECTS) 
3.32  
POST-IMPLANT BLOOD COLLECTION (SERUM GLYCEROL) NOT DONE WITHIN 120 MINUTES OF RESTARTING THE HEART (ONLY REQUIRED FOR 120 SUBJECTS) 
3.27 
OTHER PROCEDURE DEVIATION 
 
DISCHARGE 
4.01  
DISCHARGE OR 10-DAY ECHOCARDIOGRAM NOT DONE 
4.02  
DISCHARGE OR 10-DAY ECHOCARDIOGRAM DONE > 10 DAYS POST IMPLANT DATE 
4.03  
DISCHARGE PHYSICAL ASSESSMENT / VITAL SIGNS NOT DONE 
4.04  
DISCHARGE ELECTROCARDIOGRAM NOT DONE 
4.05  
DISCHARGE COAGULATION PROFILE NOT DONE 
4.07  
DISCHARGE MEDICATIONS NOT ASSESSED 
4.09  
DISCHARGE HOSPITALIZATION TIMES NOT COLLECTED 
4.08  
OTHER DISCHARGE DEVIATION 
 
1 MONTH 
5.01  
1 MONTH- SUBJECT NOT CONTACTED 
5.01  
1 MONTH- MISSED VISIT- SUBJECT CONTACTED 
5.02  
1 MONTH- ASSESSMENT NOT DONE WITHIN FOLLOW-UP WINDOW 
5.03      1 MONTH -  NYHA NOT DONE 
5.04   1 MONTH -  MEDICATIONS NOT ASSESSED 
5.05 
1 MONTH - OTHER DEVIATION 
 
3 MONTH 
6.01  
 3 MONTH -  SUBJECT NOT CONTACTED 
6.01  
 3 MONTH -  MISSED VISIT- SUBJECT CONTACTED 
6.02  
 3 MONTH -  ASSESSMENT NOT DONE WITHIN FOLLOW-UP WINDOW 
6.03  
 3 MONTH -  PHYSICAL ASSESSMENT / VITAL SIGNS NOT DONE 
6.04  
 3 MONTH -  NYHA NOT DONE 
6.05  
 3 MONTH -  ELECTROCARDIOGRAM NOT DONE 
6.06  
 3 MONTH -  ELECTROCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
6.07  
 3 MONTH -  ECHOCARDIOGRAM NOT DONE 
6.08  
 3 MONTH -  ECHOCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
6.09  
 3 MONTH -  BLOOD NOT DONE 
6.10  
 3 MONTH -  BLOOD INCOMPLETE 
6.11  
 3 MONTH -  COAGULATION PROFILE NOT DONE 
6.12  
 3 MONTH -  BLOOD NOT DONE WITHIN FOLLOW-UP WINDOW 
6.13  
 3 MONTH -  MEDICATIONS NOT ASSESSED 
6.14  
 3 MONTH -  MEDICATIONS NOT ASSESSED WITHIN FOLLOW-UP WINDOW 
6.15  
 3 MONTH -  OTHER DEVIATION 

Edwards Lifesciences LLC      
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Protocol Number: 2012-02 
 
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1 YEAR 
8.01 
 1 YEAR - SUBJECT NOT CONTACTED 
8.01 
 1 YEAR – MISSED VISIT- SUBJECT CONTACTED 
8.02  
 1 YEAR - ASSESSMENT NOT DONE WITHIN FOLLOW-UP WINDOW 
8.03  
 1 YEAR - PHYSICAL ASSESSMENT / VITAL SIGNS NOT DONE 
8.04  
 1 YEAR - NYHA NOT DONE 
8.05  
 1 YEAR - ELECTROCARDIOGRAM NOT DONE 
8.06  
 1 YEAR - ELECTROCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
8.07 
 1 YEAR - ECHOCARDIOGRAM NOT DONE 
8.08 
 1 YEAR - ECHOCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
8.09 
 1 YEAR - BLOOD NOT DONE 
8.10 
 1 YEAR - BLOOD INCOMPLETE 
8.11 
 1 YEAR - COAGULATION PROFILE NOT DONE 
8.12  
1 YEAR - BLOOD NOT DONE WITHIN FOLLOW-UP WINDOW 
8.13  
1 YEAR - MEDICATIONS NOT ASSESSED 
8.14  
1 YEAR - MEDICATIONS NOT ASSESSED WITHIN FOLLOW-UP WINDOW 
8.16 
1 YEAR- QUALITY OF LIFE NOT DONE 
8.15  
1 YEAR - OTHER DEVIATION 
 
2 YEAR 
9.01 
 2 YEAR - SUBJECT NOT CONTACTED 
9.01 
 2 YEAR –MISSED VISIT- SUBJECT CONTACTED 
9.02 
 2 YEAR - ASSESSMENT NOT DONE WITHIN FOLLOW-UP WINDOW 
9.03 
 2 YEAR - PHYSICAL ASSESSMENT / VITAL SIGNS NOT DONE 
9.04 
 2 YEAR - NYHA NOT DONE 
9.05 
 2 YEAR - ELECTROCARDIOGRAM NOT DONE 
9.06  
2 YEAR - ELECTROCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
9.07  
2 YEAR - ECHOCARDIOGRAM NOT DONE 
9.08  
2 YEAR - ECHOCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
9.09  
2 YEAR - BLOOD NOT DONE 
9.10  
2 YEAR - BLOOD INCOMPLETE 
9.11  
2 YEAR - COAGULATION PROFILE NOT DONE 
9.12 
2 YEAR- BLOOD NOT DONE WITHIN FOLLOW-UP WINDOW 
9.13  
2 YEAR - MEDICATIONS NOT ASSESSED 
9.14  
2 YEAR - MEDICATIONS NOT ASSESSED WITHIN FOLLOW-UP WINDOW 
9.15  
2 YEAR - OTHER DEVIATION 
 
 
 
 
 
 

Edwards Lifesciences LLC      
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Protocol Number: 2012-02 
 
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3 YEAR 
10.01  3 YEAR - SUBJECT NOT CONTACTED 
10.01  3 YEAR – MISSED VISIT- SUBJECT CONTACTED 
10.02  3 YEAR - ASSESSMENT NOT DONE WITHIN FOLLOW-UP WINDOW 
10.03  3 YEAR - PHYSICAL ASSESSMENT / VITAL SIGNS NOT DONE 
10.04  3 YEAR - NYHA NOT DONE 
10.05  3 YEAR - ELECTROCARDIOGRAM NOT DONE 
10.06  3 YEAR - ELECTROCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
10.07  3 YEAR - ECHOCARDIOGRAM NOT DONE 
10.08  3 YEAR - ECHOCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
10.09  3 YEAR - BLOOD NOT DONE 
10.10  3 YEAR - BLOOD INCOMPLETE 
10.11  3 YEAR - COAGULATION PROFILE NOT DONE  
10.12  3 YEAR - BLOOD NOT DONE WITHIN FOLLOW-UP WINDOW 
10.13  3 YEAR - MEDICATIONS NOT ASSESSED 
10.14  3 YEAR - MEDICATIONS NOT ASSESSED WITHIN FOLLOW-UP WINDOW 
10.15  3 YEAR - OTHER DEVIATION 
 
4 YEAR 
11.01  4 YEAR - SUBJECT NOT CONTACTED 
11.01  4 YEAR – MISSED VISIT- SUBJECT CONTACTED 
11.02  4 YEAR - ASSESSMENT NOT DONE WITHIN FOLLOW-UP WINDOW 
11.03  4 YEAR - PHYSICAL ASSESSMENT / VITAL SIGNS NOT DONE 
11.04  4 YEAR - NYHA NOT DONE 
11.05  4 YEAR - ELECTROCARDIOGRAM NOT DONE 
11.06  4 YEAR - ELECTROCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
11.07  4 YEAR - ECHOCARDIOGRAM NOT DONE 
11.08  4 YEAR - ECHOCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
11.09  4 YEAR - BLOOD NOT DONE 
11.10  4 YEAR - BLOOD INCOMPLETE 
11.11 4 YEAR - COAGULATION PROFILE NOT DONE 
11.12  4 YEAR - BLOOD NOT DONE WITHIN FOLLOW-UP WINDOW 
11.13  4 YEAR - MEDICATIONS NOT ASSESSED 
11.14  4 YEAR - MEDICATIONS NOT ASSESSED WITHIN FOLLOW-UP WINDOW 
11.15  4 YEAR - OTHER DEVIATION 
 
 
 
 
 
 
 
 

Edwards Lifesciences LLC      
                                                                                                                                                                                                                           ATTACHMENTS 
 
Clinical Investigational Plan 
Protocol Number: 2012-02 
 
CONFIDENTIAL AND PROPRIETATARY DATA: This document and the information contained herein may not be reproduced, used, or disclosed without written permission from Edwards Lifesciences LLC 
 
 
 
 
 
 
 
5 YEAR 
12.01  5 YEAR - SUBJECT NOT CONTACTED 
12.01  5 YEAR – MISSED VISIT - SUBJECT CONTACTED 
12.02  5 YEAR - ASSESSMENT NOT DONE WITHIN FOLLOW-UP WINDOW 
12.03  5 YEAR - PHYSICAL ASSESSMENT / VITAL SIGNS NOT DONE 
12.04  5 YEAR - NYHA NOT DONE 
12.05  5 YEAR - ELECTROCARDIOGRAM NOT DONE 
12.06  5 YEAR - ELECTROCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
12.07  5 YEAR - ECHOCARDIOGRAM NOT DONE 
12.08  5 YEAR - ECHOCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
12.09  5 YEAR - BLOOD NOT DONE 
12.10  5 YEAR - BLOOD INCOMPLETE 
12.11  5 YEAR - COAGULATION PROFILE NOT DONE  
12.12  5 YEAR - BLOOD NOT DONE WITHIN FOLLOW-UP WINDOW 
12.13  5 YEAR - MEDICATIONS NOT ASSESSED 
12.14  5 YEAR - MEDICATIONS NOT ASSESSED WITHIN FOLLOW-UP WINDOW 
12.15  5 YEAR - OTHER DEVIATION 
 
6 year 
16.01  6 YR - SUBJECT NOT CONTACTED 
16.01  6 YR – MISSED VISIT - SUBJECT CONTACTED 
16.02  6 YR - ASSESSMENT NOT DONE WITHIN FOLLOW-UP WINDOW 
16.03  6 YR - PHYSICAL ASSESSMENT / VITAL SIGNS NOT DONE 
16.04  6 YR - NYHA NOT DONE 
16.05  6 YR - ELECTROCARDIOGRAM NOT DONE 
16.06  6 YR - ELECTROCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
16.07  6 YR - ECHOCARDIOGRAM NOT DONE 
16.08  6 YR - ECHOCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
16.09  6 YR - BLOOD NOT DONE 
16.10  6 YR - BLOOD INCOMPLETE 
16.11  6 YR - COAGULATION PROFILE NOT DONE  
16.12  6 YR - BLOOD NOT DONE WITHIN FOLLOW-UP WINDOW 
16.13  6 YR - MEDICATIONS NOT ASSESSED 
16.14  6 YR - MEDICATIONS NOT ASSESSED WITHIN FOLLOW-UP WINDOW 
16.15  6 YR - OTHER DEVIATION 
 
 
 
 
 
 

Edwards Lifesciences LLC      
                                                                                                                                                                                                                           ATTACHMENTS 
 
Clinical Investigational Plan 
Protocol Number: 2012-02 
 
CONFIDENTIAL AND PROPRIETATARY DATA: This document and the information contained herein may not be reproduced, used, or disclosed without written permission from Edwards Lifesciences LLC 
 
 
 
 
 
 
 
7 year 
17.01  7 YR - SUBJECT NOT CONTACTED 
17.01  7 YR – MISSED VISIT - SUBJECT CONTACTED 
17.02  7 YR - ASSESSMENT NOT DONE WITHIN FOLLOW-UP WINDOW 
17.03  7 YR - PHYSICAL ASSESSMENT / VITAL SIGNS NOT DONE 
17.04  7 YR - NYHA NOT DONE 
17.05  7 YR - ELECTROCARDIOGRAM NOT DONE 
17.06  7 YR - ELECTROCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
17.07  7 YR - ECHOCARDIOGRAM NOT DONE 
17.08  7 YR - ECHOCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
17.09  7 YR - BLOOD NOT DONE 
17.10  7 YR - BLOOD INCOMPLETE 
17.11  7 YR - COAGULATION PROFILE NOT DONE  
17.12  7 YR - BLOOD NOT DONE WITHIN FOLLOW-UP WINDOW 
17.13  7 YR - MEDICATIONS NOT ASSESSED 
17.14  7 YR - MEDICATIONS NOT ASSESSED WITHIN FOLLOW-UP WINDOW 
17.15  7 YR - OTHER DEVIATION 
8 year 
18.01  8 YR - SUBJECT NOT CONTACTED 
18.01  8 YR – MISSED VISIT - SUBJECT CONTACTED 
18.02  8 YR - ASSESSMENT NOT DONE WITHIN FOLLOW-UP WINDOW 
18.03  8 YR - PHYSICAL ASSESSMENT / VITAL SIGNS NOT DONE 
18.04  8 YR - NYHA NOT DONE 
18.05  8 YR - ELECTROCARDIOGRAM NOT DONE 
18.06  8 YR - ELECTROCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
18.07  8 YR - ECHOCARDIOGRAM NOT DONE 
18.08  8 YR - ECHOCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
18.09  8 YR - BLOOD NOT DONE 
18.10  8 YR - BLOOD INCOMPLETE 
18.11  8 YR - COAGULATION PROFILE NOT DONE  
18.12  8 YR - BLOOD NOT DONE WITHIN FOLLOW-UP WINDOW 
18.13  8 YR - MEDICATIONS NOT ASSESSED 
18.14  8 YR - MEDICATIONS NOT ASSESSED WITHIN FOLLOW-UP WINDOW 
18.15  8 YR - OTHER DEVIATION 
 
 
 
 
 
 
 
 

Edwards Lifesciences LLC      
                                                                                                                                                                                                                           ATTACHMENTS 
 
Clinical Investigational Plan 
Protocol Number: 2012-02 
 
CONFIDENTIAL AND PROPRIETATARY DATA: This document and the information contained herein may not be reproduced, used, or disclosed without written permission from Edwards Lifesciences LLC 
 
 
 
 
 
 
 
9 year 
19.01  9 YR - SUBJECT NOT CONTACTED 
19.01  9 YR – MISSED VISIT - SUBJECT CONTACTED 
19.02  9 YR - ASSESSMENT NOT DONE WITHIN FOLLOW-UP WINDOW 
19.03  9 YR - PHYSICAL ASSESSMENT / VITAL SIGNS NOT DONE 
19.04  9 YR - NYHA NOT DONE 
19.05  9 YR - ELECTROCARDIOGRAM NOT DONE 
19.06  9 YR - ELECTROCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
19.07  9 YR - ECHOCARDIOGRAM NOT DONE 
19.08  9 YR - ECHOCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
19.09  9 YR - BLOOD NOT DONE 
19.10  9 YR - BLOOD INCOMPLETE 
19.11  9 YR - COAGULATION PROFILE NOT DONE  
19.12  9 YR - BLOOD NOT DONE WITHIN FOLLOW-UP WINDOW 
19.13  9 YR - MEDICATIONS NOT ASSESSED 
19.14  9 YR - MEDICATIONS NOT ASSESSED WITHIN FOLLOW-UP WINDOW 
19.15  9 YR - OTHER DEVIATION 
 
10 year 
20.01  10 YR - SUBJECT NOT CONTACTED 
20.01  10 YR – MISSED VISIT - SUBJECT CONTACTED 
20.02  10 YR - ASSESSMENT NOT DONE WITHIN FOLLOW-UP WINDOW 
20.03  10 YR - PHYSICAL ASSESSMENT / VITAL SIGNS NOT DONE 
20.04  10 YR - NYHA NOT DONE 
20.05  10 YR - ELECTROCARDIOGRAM NOT DONE 
20.06  10 YR - ELECTROCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
20.07  10 YR - ECHOCARDIOGRAM NOT DONE 
20.08  10 YR - ECHOCARDIOGRAM NOT DONE WITHIN FOLLOW-UP WINDOW 
20.09  10 YR - BLOOD NOT DONE 
20.10  10 YR - BLOOD INCOMPLETE 
20.11  10 YR - COAGULATION PROFILE NOT DONE 
20.12  10 YR - BLOOD NOT DONE WITHIN FOLLOW-UP WINDOW 
20.13  10 YR - MEDICATIONS NOT ASSESSED 
20.14  10 YR - MEDICATIONS NOT ASSESSED WITHIN FOLLOW-UP WINDOW 
20.15  10 YR - OTHER DEVIATION 
 
Adverse Event 
14.01  UADE NOT REPORTED WITHIN 10 WORKING DAYS OF THE INVESTIGATOR AWARENESS DATE 
14.02  OTHER ADVERSE EVENT DEVIATION 
 
Miscellaneous 
15.01  STUDY DEVICE USED IN A SUBJECT NOT ENROLLED IN THE STUDY 
15.02  OTHER DEVIATION 

EDWARDS LIFESCIENCES LLC 
CLINICAL INVESTIGATIONAL PLAN 
PROTOCOL NUMBER: 2012-02 
 
ATTACHMENTS 
 
CONFIDENTIAL AND PROPRIETATARY DATA: This document and the information contained herein may not be reproduced, used, or disclosed 
without written permission from Edwards Lifesciences LLC 
REVISION J: 03 MARCH 2021 
 
 
 
ATTACHMENT M – DEVICE DEFICIENCY CODES 

Edwards Lifesciences 
LLC 
 
ATTACHMENTS
 
 
Clinical Investigational Plan 
Protocol Number: 2012-02 
 
CONFIDENTIAL AND PROPRIETATARY DATA: This document and the information contained herein may not be reproduced, used, or disclosed 
without written permission from Edwards Lifesciences LLC 
 
 
 
 
DEVICE DEFICIENCY CODES 
 
Code 
Label 
DD.2 
Valve / Holder 
DD.2.01 
Device function, packaging not intact 
DD.2.02 
Device function, component contamination 
DD.2.03 
Device function, unable to remove from jar 
DD.2.04 
Device function, unable to place sutures through sewing ring 
DD.2.05 
Device function, unable to position on the annulus 
DD.2.06 
Device function, bioprosthesis and holder separate during procedure 
DD.2.07 
Device function, other, specify 
DD.2.08 
Device use, sizing technique 
DD.2.09 
Device use, sterility compromised  
DD.2.10 
Device use, used expired product 
DD.2.11 
Device use, component damaged by operator 
DD.2.12 
Device use, improper positioning 
DD.2.13 
Device use, other specify 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

EDWARDS LIFESCIENCES LLC 
CLINICAL INVESTIGATIONAL PLAN 
PROTOCOL NUMBER: 2012-02 
 
ATTACHMENTS 
 
CONFIDENTIAL AND PROPRIETATARY DATA: This document and the information contained herein may not be reproduced, used, or disclosed 
without written permission from Edwards Lifesciences LLC 
REVISION J: 03 MARCH 2021 
 
 
 
ATTACHMENT N – CLINICAL TRIAL AGREEMENT 
 
 
No Longer In Use 
 
 
 

EDWARDS LIFESCIENCES LLC 
 
ATTACHMENTS 
CLINICAL INVESTIGATIONAL PLAN 
PROTOCOL NUMBER: 2012-02 
CONFIDENTIAL AND PROPRIETATARY DATA: THIS DOCUMENT AND THE INFORMATION CONTAINED HEREIN MAY NOT BE REPRODUCED, USED, OR DISCLOSED 
WITHOUT WRITTEN PERMISSION FROM EDWARDS LIFESCIENCES LLC 
REVISION J: 03 MARCH 2021 
 
 
 
 
 
ATTACHMENT O – POWER SIMULATION CODE FOR PRIMARY SAFETY 
ENDPOINT 
 
No Longer In Use