Carpentier-Edwards® Perimount Magna® Mitral Pericardial Bioprostheses Models 7000/7000 TFX and Carpentier-Edwards® Perimount Magna® Mitral Ease™ Pericardial Bioprostheses Models 7200TFX and 7300/7300TFX
Phase: NA
Conditions: Coronary Artery Disease, Mitral Valve Regurgitation, Mitral Valve Incompetence, Heart Failure
Sponsor: Edwards Lifesciences

 This document and the information contained herein is considered Proprietary and Confidential  
and may not be reproduced, used or disclosed without written permission from Edwards Lifesciences LLC. 
 
 
- 1 of 80  - 
 
 
POST-APPROVAL STUDY PROTOCOL 
STUDY# 2006-05 
 
CARPENTIER-EDWARDS PERIMOUNT MAGNA MITRAL 
PERICARDIAL BIOPROSTHESES MODELS 7000/7000TFX 
and 
CARPENTIER-EDWARDS PERIMOUNT MAGNA MITRAL 
EASE™ PERICARDIAL BIOPROSTHESIS MODEL 7200TFX and 
7300/7300TFX 
 
Protocol Change Status 
Protocol Revision # 
Revision Date 
Revision A 
(Not implemented) 
January 23, 2007 
Revision B 
(Implemented in the European Community) 
May 23, 2007 
Revision C 
(Not implemented) 
July 17, 2007 
Revision D 
(United States and European Community) 
September 25, 2008 
Revision E 
(United States and European Community) 
January 23, 2009 
Revision F 
(United States only) 
November 24, 2009 
Revision G  
(Not implemented) 
September 17,  2010 
Revision H 
(United States and European Community) 
May 24, 2011 
Revision  I 
(United States and European Community) 
November 18 , 2013 
 
 
 
 
 
 
 

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- pg 2 of 80 - 
 
 
 
Sponsor 
Edwards Lifesciences, LLC 
One Edwards Way 
Irvine, CA  92656 
Tel: 001-949-250-0500 
Fax: 001-949-250-3630  
 

Magna Mitral Post Approval Study Protocol 2006-05 
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- 3 of 80  -
TABLE OF CONTENTS 
1.0  STUDY SUMMARY ......................................................................................................................................... 6 
2.0  INTRODUCTION ............................................................................................................................................. 9 
2. 1 
BACKGROUND
9 
2.1 
MITRAL VALVE REPLACEMENT 
10 
2.2 
MULTIPLE VALVE REPLACEMENT 
10 
2.3 
TRICUSPID VALVE REPAIR 
11 
2.4  
STUDY VALVES 
11 
3.0   STUDY OVERVIEW ...................................................................................................................................... 13 
3.1 
PURPOSE 
13 
3.2 
INDICATIONS FOR USE 
13 
3.3 
ENDPOINTS 
13 
3.3.1 
Primary Safety Endpoints .......................................................................................................... 13 
3.3.2 
Secondary Safety Endpoints ...................................................................................................... 13 
3.3.3 
Primary Effectiveness Endpoints ............................................................................................... 14 
3.3.4 
Secondary Effectiveness Endpoints ........................................................................................... 14 
4.0   STUDY DESIGN ............................................................................................................................................. 16 
4.1 
SITE SELECTION 
16 
4.2 
STUDY TIMELINE 
16 
4.4 
STUDY POPULATION 
18 
4.5  
STUDY ELIGIBILITY AND ENROLLMENT 
19 
4.6 
TIMING OF INFORMED CONSENT 
19 
4.7  
INCLUSION CRITERIA 
20 
4.8  
EXCLUSION CRITERIA 
20 
5.0  STUDY MATERIALS .................................................................................................................................... 22 
5.1  
DEVICE DESCRIPTION 
22 
5.2 
PRE-CLINICAL STUDIES 
24 
6.0  STUDY PROCEDURES ................................................................................................................................. 25 
6.1 
PREOPERATIVE PROCEDURES 
25 
6.2 
OPERATIVE PROCEDURES 
26 
6.3 
POSTOPERATIVE PROCEDURES 
27 
6.1.1 
Hospital Discharge .................................................................................................................... 27 
6.1.2 
Late Post-Operative Follow- Up ............................................................................................... 29 
6.4 
UNSCHEDULED VISITS 
31 
6.5  
MISSED VISIT 
31 
6.6 
LOST TO FOLLOW-UP 
31 
6.7 
TIME PERIODS FOR COMPLETING STUDY VISITS 
32 
6.8 
VALVE EXPLANTS 
32 
6.9  
DEATHS/AUTOPSY REPORTS 
33 
6.10  SUBJECT WITHDRAWAL 
33 
6.11 
CORE LABORATORY 
34 
7.0  ADVERSE EVENTS ....................................................................................................................................... 35 
7.1 
ADVERSE EVENT REPORTS 
37 

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7.2 
MEDICAL DEVICE REPORTING (MDR) 
38 
7.3 
MEDICAL DEVICE REPORTING OUTSIDE THE UNITED STATES 
38 
8.0   RISK ANALYSIS ............................................................................................................................................ 38 
8.1 
POTENTIAL RISKS 
39 
8.2 
MINIMIZATION OF RISKS 
40 
8.2.1 
Physician Training .................................................................................................................... 40 
8.2.2 
Clinical Events Review Committee ............................................................................................ 41 
8.2.3 
Echocardiography Core Laboratory ......................................................................................... 41 
8.2.4 
Data Quality Assurance ............................................................................................................. 42 
8.3 
POTENTIAL BENEFITS 
42 
8.4 
RISK /BENEFIT ANALYSIS 
44 
9.0 STATISTICAL ANALYSIS ........................................................................................................................... 45 
9.1 
SAMPLE SIZE CALCULATION 
45 
9.2 
ANALYSIS POPULATION 
47 
9.3 SAFETY ANALYSIS ...................................................................................................................................... 47 
9.3.1 
Primary Safety Endpoint............................................................................................................ 47 
9.4  
SECONDARY SAFETY ENDPOINTS 
48 
9.4.1 
Blood Data ................................................................................................................................. 48 
9.4.2 
Time to Death, Reoperation, and Explant ................................................................................. 49 
9.5  
EFFECTIVENESS ANALYSIS 
49 
9.5.1 
Subject Functional Classification .............................................................................................. 50 
9.5.2 
Hemodynamic Performance ...................................................................................................... 50 
9.6  
POOLABILITY 
50 
9.7  
MISSING DATA 
51 
10.0 ETHICAL AND REGULATORY CONSIDERATIONS............................................................................ 52 
10.1 
SUBJECT INFORMED CONSENT AND INSTITUTIONAL REVIEW BOARD/ETHICAL REVIEW COMMITTEE 
52 
10.2  HEALTH ECONOMIC INFORMATION 
53 
10.3 
CASE REPORT FORMS (CRFS) 
53 
10.4 
STUDY TERMINATION 
54 
10. 5 RECORD RETENTION 
54 
10.6  STUDY RESPONSIBILITIES 
55 
10.6.1  
Investigator Responsibilities ...................................................................................................... 55 
10.6.2  
Study Monitor/Sponsor Responsibilities .................................................................................... 57 
10.6.3 
Clinical Monitor ........................................................................................................................ 57 
10. 7  STUDY CHANGES 
58 
10. 8  IMPLANT DATA CARD 
58 
10.9  STUDY PUBLICATION 
59 
11.0  REFERENCES .............................................................................................................................................. 60 
12.0  APPENDIX 1- STS GUIDELINES FOR REPORTING MORBIDITY AND MORTALITY AFTER 
CARDIAC VALVULAR OPERATIONS ................................................................................................... 63 
13.0  APPENDIX 2: SAMPLE SUBJECT INFORMED CONSENT FORM AND HIPAA 
AUTHORIZATION ...................................................................................................................................... 64 
14.0  APPENDIX 3: ECHO CORE LAB PROTOCOL ...................................................................................... 72 

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15.0  APPENDIX 4: INSTRUCTIONS FOR USE .............................................................................................. 73 
16.0  APPENDIX 5: CASE REPORT FORMS ................................................................................................... 74 
17.0  APPENDIX 6: QUALITY OF LIFE SURVEY .......................................................................................... 75 
18.0  APPENDIX 7: IMPLANT DATA CARD ................................................................................................... 76 
19.0  APPENDIX 8:  ADVERSE EVENT DEFINITIONS ................................................................................. 79 
20.0  APPENDIX 9:  CLINICAL RISK ASSESSMENT .................................................................................... 80 

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1.0  
STUDY SUMMARY  
 
Protocol No: 
2006-05 
Study Title 
Post Approval  Study 2006-05 Carpentier-Edwards® PERIMOUNT® Magna 
Mitral Pericardial Bioprostheses Models 7000/7000TFX and Carpentier-
Edwards® PERIMOUNT® Magna Mitral Ease™ Pericardial Bioprostheses 
Models 7200TFX and 7300/7300TFX  
Study Purpose: 
To evaluate the long term safety and effectiveness of the Carpentier-Edwards® 
PERIMOUNT® Magna Mitral Bioprostheses Models 7000/7000TFX and the 
Carpentier-Edwards® PERIMOUNT®  Magna Mitral Ease™ Pericardial 
Bioprostheses Models 7200TFX and 7300/7300TFX in patients undergoing 
mitral valve replacement with or without concomitant procedures requiring 
cardiopulmonary bypass. 
Study Device: 
Carpentier-Edwards® PERIMOUNT® Magna Mitral Pericardial Bioprostheses, 
Models 7000/7000TFX and Carpentier-Edwards® PERIMOUNT® Magna Mitral 
Ease™ Pericardial Bioprostheses Models 7200TFX and 7300/7300TFX 
Study Design: 
This is a prospective, single-arm, multi-center study to be conducted in the US 
and outside the US (OUS). This study will enroll a minimum of 250 subjects 
implanted with the study valve in order to achieve 101 mitral valve replacement 
subjects who complete follow-up for a minimum of 8 years. 
Study 
Population: 
Male and female patients, 18 years or older, requiring replacement for a 
diseased, damaged, or malfunctioning native or prosthetic mitral valve. 
Entry Criteria: 
Patients will preoperatively sign the subject informed consent form, and meet 
all inclusion criteria and none of the exclusion criteria to participate in this 
clinical study. 
Duration of 
Participation: 
After the valve implantation, subjects will be followed and assessed at 
discharge, 6-months, one year, and annually thereafter for a minimum of 8 
years. 
 

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Clinical 
Endpoints: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Primary Safety
 
Linearized rates of: 
  
• 
Thromboembolism  
• 
All hemorrhage  
• 
All perivalvular leak  
• 
Endocarditis 
 
Early and late linearized and actuarial rates of: 
Secondary Safety  
• 
Thromboembolism 
• 
Valve thrombosis 
• 
All hemorrhage 
• 
Major hemorrhage 
• 
All perivalvular leak 
• 
Major perivalvular leak 
• 
Endocarditis  
• 
Hemolysis 
• 
Structural valve deterioration 
• 
Non-structural valve dysfunction 
• 
Reoperation 
• 
Explant 
• 
Death 
• 
Valve-related death 
 
Blood Studies to assess hemolysis and adverse events.   
• 
white blood count 
• 
red blood count 
• 
hematocrit  
• 
plasma free hemoglobin (or haptoglobin and SLDH) 
• 
platelet count  
• 
reticulocyte counts 
 

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Percentage of subjects in NYHA Functional Class I or II at 8 years 
post implant. 
Primary Effectiveness: 
 
Hemodynamic Performance at 8 years post implant: 
Secondary Effectiveness: 
• 
Peak gradient 
• 
Mean gradient 
• 
Effective orifice area (EOA) 
• 
EOA index 
• 
Performance index 
• 
Cardiac output 
• 
Cardiac index 
• 
Severity of mitral regurgitation 
• 
Left ventricular mass regression 
 
Quality of Life Survey (EQ-5D)  
Study Sponsor: 
Edwards Lifesciences LLC 
One Edwards Way 
Irvine, CA  92614 USA 
Telephone:   001 949-250-2500 
Facsimile:   
001 949-250-3630  
 
 
 
 
 
 
 
 
 
 

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- pg 9 of 80 - 
2.0  
INTRODUCTION 
2. 1 
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 
year1.  Mitral valvular heart disease is a condition that involves obstruction of the blood 
flow through the mitral heart valve or stenosis, leakage of the mitral valve, known as 
regurgitation, incompetence, or insufficiency; and combination of the two, sometimes 
referred to as mixed disease.  It may be caused by any number of factors, including 
congenital 
abnormalities, 
infection 
by 
various 
microorganisms, 
degenerative 
calcification, and rheumatic heart disease.   
 
Diseased heart 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 (constructed 
from synthetic material) or a tissue bioprosthetic valve (made primarily from animal 
tissue including bovine pericardium, or human valves from cadavers).  
 
Since Carpentier introduced improved techniques for mitral valve repair in 19712, the 
etiology and treatment of mitral valve disease have changed3. As the incidence of 
rheumatic mitral stenosis and regurgitation has decreased, mitral regurgitation caused 
by degenerative disease of the mitral apparatus and caused by the left ventricular 
dysfunction associated with coronary artery disease has become the predominant 
hemodynamic lesion of the mitral valve4. Edward et. al. reviewed data collected from 
1648 patients between January 1990 and December 1999 in northern New England, and 
noted 3.7 times increase in mitral valve repair (from 2.4 to 8.9 cases/100,000/year) 
whereas 
mitral 
valve 
replacement 
increased 
1.9 
times 
from 
(4.3 
to 
8.0 

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- pg 10 of 80 - 
cases/100,000/year). Based on the regional data they concluded 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 problems4.   
2.1 
Mitral Valve Replacement  
 
The Society of Thoracic Surgeons (STS) published an Executive Summary quantifying 
major cardiac surgical procedures performed in the United States throughout a 10 year 
period from 1998 to 2007.  The data showed an average of 4,339 isolated mitral valve 
replacements are performed per year5. The Starr-Edwards ball-and-cage mitral valve 
was the first commercially available reliable device for mitral valve replacement6. This 
device was implanted in a 52 year old patient in 1960. Since then, many generations of 
both mechanical and bioprosthetic valves have emerged.  As the first, second and third 
generations of mechanical prosthetic valves were being developed, bioprosthetic 
replacement valves were simultaneously being developed.  The advantages of 
bioprosthetic valves include a much lower frequency of thromboembolism and long-term 
anticoagulation therapy can be avoided7. The third generation of these valves included 
pericardial valves which incorporated new technology aimed at improving valve longevity 
and hemodynamic function.   
2.2 
Multiple Valve Replacement   
 
Simultaneous replacement of the mitral and aortic valves is recommended by the 
ACC/AHA 2006 Guidelines for the Management of Patients with Valvular Heart Disease 
when patients are diagnosed with regurgitation or stenosis in both the mitral and aortic 
valves when treatment by repair or valvuloplasty would not or did not have a therapeutic 
effect8.  When both aortic and mitral valves are replaced, the prostheses chosen should 
both be tissue or mechanical to balance the need for anticoagulation and projected 
longevity9.  Studies have shown that the implantation of simultaneous tissue versus 
mechanical valves has no reduction in risk of valve-related morbidity, thromboembolism, 
or late death10,11.  The STS Executive Summary indicated that 15% of patients 

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- pg 11 of 80 - 
undergoing mitral valve surgery in 2007 in the United States underwent simultaneous 
mitral and aortic valve replacement (1205/7883).  
2.3 
Tricuspid Valve Repair 
 
The most common Tricuspid Valve disease etiology in North America is tricuspid 
regurgitation secondary to left heart pathology, such as mitral valve disease and left 
heart failure12. Tricuspid regurgitation may be functional or organic. Functional tricuspid 
regurgitation is commonly caused by severe mitral valve stenosis or regurgitation, both 
of which lead to dilatation of the right ventricle and the tricuspid annulus13.  Tricuspid 
regurgitation is a significant clinical problem that may be undertreated by cardiologists 
and surgeons14. Tricuspid dilation secondary to mitral regurgitation is often unrecognized 
as tricuspid regurgitation15,16,17.   The ACC/AHA 2006 Guidelines for the Management of 
Patients with Valvular Heart Disease recommend concomitant tricuspid annuloplasty to 
be considered at time of mitral valve surgery, especially if there are preoperative signs or 
symptoms of right-sided heart failure.  This would alleviate the risk of severe persistent 
TR and the need for another surgery.  The European Society of Cardiology 2007 
Guidelines on the Management of Valvular Heart Disease point out that the relative 
simplicity of tricuspid valve repair along with the high risk of secondary surgical 
correction are incentives for earlier tricuspid repair.  Furthermore, reoperation on the 
tricuspid valve after mitral valve surgery in persistent tricuspid regurgitation carries a 
high risk due to the clinical condition of the patients, including advanced age and the 
number of previous cardiac interventions, and may result in poor long-term results due to 
irreversible right ventricular dysfunction18.  
2.4  
Study Valves 
 
The Carpentier-Edwards PERIMOUNT Magna Mitral pericardial bioprostheses, 
models 7000/7000TFX and Carpentier-Edwards PERIMOUNT Magna Mitral Ease™ 
Pericardial Bioprostheses Models 7200TFX and 7300/7300TFX  (also referred to as the 
Magna Mitral valves) are built upon the same proven wireform frame and leaflet 
attachment as the Carpentier-Edwards PERIMOUNT mitral pericardial bioprostheses 

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- pg 12 of 80 - 
models 6900, 6900P and 6900PTFX.  Valves are available in the sewing ring diameters 
and sizes shown below in Section 5, Table 3.   
 
The Magna Mitral valve model 7000TFX received European CE marking in August 2005 
and Canadian approval in November 2005.  Models 7000 and 7000TFX, received 
Australian approval in July 2008 and FDA approval in August 2008 (sizes 25 mm – 33 
mm (P860057/S029).  More than 4000 Magna Mitral 7000TFX valves had been sold 
worldwide as of August 2008.The Magna Mitral model 7200TFX received FDA approval 
on July 09, 2009 (P860057/S56). Models 7300/7300TFX received FDA approval in June 
24,2010 (P860057/S68). 
 
Table 1: Magna Mitral Device Approvals by Region  
 
Region 
Approval Date 
Valve Model(s) 
European Community 
August 2005 
7000 TFX 
Canada 
November 2005 
7000 TFX 
Australia 
July 2008 
7000/7000 TFX 
United States 
July 2009 
7200TFX 
European Community 
August 2010  
7300/7300 TFX 
United States 
June 2010  
7300/7300 TFX 
 
 
 
 
 

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3.0   STUDY OVERVIEW  
3.1 
Purpose 
 
 
The purpose of this study is to evaluate the long term safety and effectiveness of the 
Magna Mitral valves in patients undergoing mitral valve replacement with or without 
concomitant procedures requiring cardiopulmonary bypass. 
3.2 
Indications for Use 
 
The Carpentier-Edward PERIMOUNT Magna Mitral and Magna Mitral Ease 
bioprostheses are indicated for use in patients who require replacement of their native or 
prosthetic mitral valve.    
3.3 
Endpoints 
3.3.1  Primary Safety Endpoints  
Long term safety performance will be evaluated by comparing the linearized 
rates listed below to the objective performance criteria referenced in ISO 5840-
2005, Cardiovascular Implants-Cardiac Valve Prostheses 
• 
Thromboembolism 
• 
All Hemorrhage 
• 
All Perivalvular Leak 
• 
Endocarditis 
3.3.2 Secondary Safety Endpoints 
Secondary safety endpoints will include early and late linearized and actuarial 
analysis of the following: 
• 
Thromboembolism 
• 
Valve thrombosis 
• 
All hemorrhage 
• 
Major hemorrhage 

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- pg 14 of 80 - 
• 
All perivalvular leak 
• 
Major perivalvular leak 
• 
Endocarditis  
• 
Hemolysis 
• 
Structural valve deterioration 
• 
Non-structural valve dysfunction 
• 
Reoperation 
• 
Explant 
• 
Death 
• 
Valve-related death 
Blood studies including white blood count, red blood count, hematocrit, plasma 
free hemoglobin (or haptoglobin and SLDH), platelet and reticulocyte counts will 
be used to evaluate the rate of hemolysis and adverse events at the 6 month, 1 
year and annual follow-up visits. 
3.3.3 Primary Effectiveness Endpoints  
The primary effectiveness endpoint will be the percentage of subjects in NYHA 
functional classification I or II at 8 years post-implant  
3.3.4 Secondary Effectiveness Endpoints  
The secondary Effectiveness endpoints will be: 
Hemodynamic Performance by echocardiography at 8 years post implant, which 
includes: 
• 
Peak Gradient 
• 
Mean Gradient 
• 
Effective Orifice Area 
• 
Effective Orifice Area Index 
• 
Performance Index 
• 
Cardiac Output  
• 
Cardiac Index 

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- pg 15 of 80 - 
• 
Severity of Valvular Regurgitation 
• 
LV Mass Regression  
Quality of Life Survey (EQ-5D) at 6 month post index procedure as compared to 
preoperative baseline. 
 

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4.0   STUDY DESIGN 
 
This study has been designed as a prospective, multi-center post-approval study to be 
conducted in the United States (US) and outside the United States (OUS).  A minimum of 250 
subjects will be enrolled to obtain long term data from at least 101 subjects who have completed 
8 years of post-implant follow-up.  Of these 250, approximately 38 (15%) are anticipated to be 
simultaneous aortic and mitral replacements.  Subject enrollment will not start in the US before 
obtaining FDA approval.  
4.1 
Site Selection 
 
Up to 25 sites will enroll subjects in this study.  Participating sites will be chosen based 
on their experience in conducting clinical studies, implanting bioprostheses, academic 
and medical reputation, and their ability to enroll the required study subject population. 
Study centers will be required to have a study coordinator to assist the primary 
investigator(s), and study participating center must have the time and resources 
available to participate in this study. 
 
Study sites will be in the United States, and OUS (Outside the US, i.e. Canada, Europe, 
Asia Pacific, Israel).  On average, each site is expected to enroll at least 15 subjects. It is 
anticipated that each of the participating sites will have a Principal Investigator, and 
there will be up to six Co-Investigators per site, for a total of up to 140 investigators. 
Each of the operating investigators will be experienced in mitral valve replacement. 
4.2 
Study Timeline 
Subject enrollment in this study was initiated with the Magna Mitral Model 
7000/7000TFX in Europe under protocol revision B as of May 23, 2007 and in the United 
States under protocol version D as of September 25, 2008.  Internal revisions A and C 
were not reviewed or approved by FDA and were never implemented.  Internal revision 
G was submitted to FDA to request inclusion of the Magna Mitral valve model 7300 in 
the study.   Revision H was  submitted in response to FDA requests to update the 

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- pg 17 of 80 - 
statistical analysis plan to address the inclusion of double valve replacement recipients 
in the study population and include a comparison of the subject data separating the 
various valve models covered under this post approval study .  
 
The Study Timeline is revised to reflect the final study report date of December 31, 2020.  
Table 2 which follows shows the report schedule listing the original and revised scheduled 
report dates: 
 
                            Table 2: Revised Study Reporting Time 
 
Report Schedule 
Original Schedule Report Date Scheduled Report  Date 
6-Year Interim Report 
Remains the same 
August 28, 2014 
7-year Interim Report 
Remains the same 
August 28, 2015 
8-year Interim Report 
Remains the same 
August 27, 2016 
9-Year Interim Report 
This was originally intended to 
be the final report, and was to 
be submitted November 27, 
2017.  
August 27, 2017 
10-Year Interim Report 
None 
August  27, 2018 
11-Year Interim Report 
None 
August 27, 2019 
Final Report, minimum 101 
patients with 8 year follow-up 
August 27, 2017 
December 31, 2020 
 
Justification for Change in the Study Reporting Time 
 
As of November 4, 2013, a total of 249 patients had a study valve in place at discharge. 
Therefore, only one (1) additional subject must be implanted between now and December 31, 
2014, to meet the protocol requirement of 250 subjects implanted. Of the minimum 250 
implanted subjects required per revision H of study protocol (2006-05), a minimum of 101 
subjects must be followed for eight (8) years. As of November 4, 2013, we have lost the ability 
to follow 55 patients either due to death, withdrawal or removal of the study valve. This leaves 
203 who can potentially make it to the eight (8) year follow up. Currently, the longest recorded 
follow-up is five (5) years. Therefore, it will be another three (3) years before the first patient 
reaches the 8-year follow-up visit and up to six (6) years to achieve 101 patients with eight (8) 

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- pg 18 of 80 - 
year follow-up data. As a result, Edwards anticipates the final study report will be submitted in 
December 2020. 
 
Table 3. Study Enrollment by Protocol Revision by Valve Model  
Location  
Protocol 
Revision 
Revision Date 
Valve Model No(s). 
United States/Europe 
(Not implemented) 
Revision A 
January 23, 2007 
7000/7000TFX 
Europe  
Revision B. 
May 23, 2007 
7000/7000TFX 
United States/Europe 
(Not implemented) 
Revision C 
July 17, 2007 
7000/7000TFX 
United States/Europe 
Revision D 
September 25, 2008 
7000/7000TFX 
United States/Europe 
Revision E 
January 23, 2009 
7000/7000TFX 
United States 
(Northwestern University only) 
Revision F 
November 24, 2009 
7200TFX 
United States 
(Not implemented) 
Revision G 
September 17, 2010 
7300/7300TFX 
United States/Europe 
Revision H  
May 24, 2011 
7000/7000TFX/ 
7300/7300TFX  
 
Edwards continues to actively review study recruitment procedures in an ongoing effort 
to improve study enrollment rates and complete the study in a timely fashion.  
 
4.4 
Study Population 
 
The Carpentier-Edward PERIMOUNT Magna Mitral bioprostheses is indicated for 
patients who require replacement of a native or prosthetic mitral valve.   Therefore this 
post-approval study population may include patients age 18 or older who have been 
identified as a potential candidates for mitral valve replacement based on the pre-

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- pg 19 of 80 - 
operative diagnosis and intraoperative anatomical and pathological considerations as 
determined by the implanting surgeon. 
 
4.5  
Study Eligibility and Enrollment  
 
Patients who have been diagnosed with mitral valve disease for which valve 
replacement surgery is indicated may be considered for study participation at qualified 
study sites.  Patients who have been considered for study inclusion by the study 
investigator shall be listed on the Subject Screening Log.  Patients who agree to 
participate in the study and have completed approved written informed consent will be 
considered enrolled in the study and will be assigned a unique site specific sequential 
study identification numbers defined by Edwards Lifesciences.  
 
4.6 
Timing of Informed Consent  
 
Informed consent must be obtained from any potential study subject prior to conducting 
any preoperative assessments that are not part of the routine preparation and evaluation 
of a study subject for mitral valve replacement.   
 
Study subjects who complete informed consent but are found to be ineligible for study 
inclusion, shall be notified and the reason for study exclusion shall be documented on 
the Subject Screening Log. A Patient Selection case report form shall be used to 
document subject ineligibility and a Study Withdrawal case report form shall be 
completed to document the reason for subject withdrawal. No further CRFs need to be 
completed for these subjects. 
 
For subjects who are eligible for the study but who do not receive the study valve, the 
reason the subject did not receive a study valve shall be recorded on the Subject 
Screening Log.  A Patient Selection case report form and Study Withdrawal form shall 

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- pg 20 of 80 - 
also be completed to document the reason for subject withdrawal. No further CRFs need 
to be completed for these subjects.   
 
For subjects who are eligible for the study, but who ultimately receive a non-study  valve, 
the reason for use of a non-study valve shall be documented on the Subject Screening 
Log, and Patient Selection and Study Withdrawal case report forms completed.  No 
other CRFs need to be completed for these subjects. 
 
Documentation of all potential study subjects is required in order to reduce the potential 
for study subject selection bias. Subjects who are censored from the study will be 
identified and the reason for censorship will be indicated in the data analysis.  
4.7  
Inclusion Criteria 
 
1. The patient requires, as indicated in the preoperative evaluation, a replacement 
mitral valve. 
2. The patient has signed and dated the subject informed consent form prior to 
surgery. 
3. The patient is expected to survive the surgery and be discharged.  
4. The patient is geographically stable and agrees to attend follow-up assessments. 
5. The patient is 18 years or older. 
4.8  
Exclusion Criteria 
 
1. The patient has any known non-cardiac life-threatening disease, which will limit 
the patient’s life expectancy below 1 year. 
2. The patient presents with active endocarditis within the last 3 months. 
3. The patient is pregnant or lactating. 
4. The patient  is an intravenous drug abuser. 
5. The patient is currently a prison inmate. 
6. The patient  is currently participating in a study of an investigational drug or 
device. 

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- pg 21 of 80 - 
7. The patient requires replacement of a native or prosthetic tricuspid or pulmonic 
valve. 
8. The patient requires replacement of a native or prosthetic aortic valve with a 
prosthesis other than a commercially available Carpentier-Edwards PERIMOUNT 
Valve (i.e. models 2700, 2700TFX, 2800, 2800TFX, 2900, 3000, 3000TFX, 
3300TFX)*. 
9. The patient was previously enrolled in the study. 
10. The patient has had prior aortic, tricuspid and/or pulmonary valve surgery, which 
included implantation of a bioprosthetic valve or mechanical valve that will remain 
in situ. 
 
NOTE: Commercial availability may vary by region. At the time of this protocol, the 
model 2900 is not available in the United States.  
 
As of Protocol revision D, this study allows simultaneous implantation of the Magna 
Mitral valve with a concomitant replacement of the aortic valve, if the aortic valve 
replacement is performed using a commercially available Carpentier Edwards aortic 
prosthesis.    
 
 
 
 
However, if the study subject already has a valve prosthesis in the aortic, tricuspid or 
pulmonic position or requires a valve replacement of the native valve or replacement of a 
prior prosthesis in one of these positions, and this valve is intended to remain in the 
subject at the time of mitral valve replacement, the study subject should NOT be 
included in the study.  
 
 
CEP Magna Mitral 
(Models 7000/7200/7300) 
+
Simultaneous CEP Aortic 
Valve  
implantation or 
replacement 
(Models 2700, 2800, 2900, 
3000, 3300) 
Subject eligible for 
study inclusion 
Remaining Aortic, 
Tricuspid or  Pulmonic  
implant, or need for 
simultaneous  
non- CEP Aortic valve 
replacement 
Subject is NOT 
eligible for study 
inclusion 
+
CEP Magna Mitral 
(Models 
7000/7200/7300) 

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- pg 22 of 80 - 
 
 
5.0  
STUDY MATERIALS 
 
5.1  
Device Description 
 
The Carpentier-Edwards PERIMOUNT Magna Mitral and Magna Mitral Ease valves 
included in this study are modified versions of the Carpentier-Edwards PERIMOUNT 
mitral valve models 6900, 6900P and 6900PTFX.  All study valves are built upon the 
same proven wireform frame and leaflet attachment as the Model 6900 and are available 
in various sewing ring diameters and sizes shown below in Table 3.   
 
Table 4. Valve Size by Tissue Annulus Diameter  (mm) 
Tissue Annulus Diameter (TAD)  
28  
29.5  
31.5  
33.5  
33.5  
Model 7000/7000TFX  
25 
27 
29 
31 
33 
Model 7200TFX 
27 
29 
31 
33 
35 
Model 7300/7300TFX 
25 
27 
29 
31 
33 
 
These bioprostheses incorporate a sewing ring specifically designed for the mitral 
position and are the first bioengineered mitral valve design with three selected bovine 
pericardial leaflet mounted on a flexible metal alloy frame.  
 
Bovine pericardium was selected for its intrinsic properties for valve manufacture, 
notably in terms of collagen content and tolerance to high bending curvatures. Bovine 
pericardium is cross-linked using a Neutralogic fixation process in which tissue is treated 
in a stress-free bath of buffered glutaraldehyde solution. Magna Mitral valve models 
7000TFX, 7200TFX and 7300TFX are treated according to the ThermaFix process, 
which involves heat treat of the tissue in glutaraldehyde and uses ethanol and 
Polysorbate-80 (a surfactant). Glutaraldehyde has been shown to reduce the antigenicity 

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- pg 23 of 80 - 
of tissue xenograft valves and increase tissue stability.  Glutaradehyde alone has not 
been shown to affect or reduce the calcification rate of the valve. 23, 24. 
 
Tissue thickness is measured for each valve size and leaflets are die-cut in selected 
areas of the pericardial sheet.  Three leaflets matched for similar thickness and elasticity 
are then assembled and mounted underneath the lightweight wireform frame, to 
minimize commissural stress points.  The lightweight wireform frame is made of 
corrosion resistant cobalt-chromium ally, chosen for its spring efficiency and fatigue 
properties. The frame is designed to be compliant at the orifice as well as at the 
commissures. The frame is covered with a woven polyester fabric sewn with 
polyfluoroethylene thread.  The wireform frame is symmetrical and the three commissure 
supports (struts) are equally spaced.   Detailed instructions for use of the valve including 
a description of the sewing ring and valve holder system can be found for each Magna 
mitral valve model in Appendix 4.  
 
 
 
 
 
 
 
 
 
 
 
Comparison of Mitral Valve and Packaging Systems 
 
System 
Feature 
Carpentier-Edwards 
PERIMOUNT  
Magna Mitral  
7000 / 7000TFX 
 
Carpentier-Edwards 
PERIMOUNT  
Magna Mitral Ease  
7200TFX 
 
Carpentier-Edwards PERIMOUNT 
Magna Mitral Ease  
7300 / 7300TFX 
 
 

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- pg 24 of 80 - 
System 
Feature 
Carpentier-Edwards 
PERIMOUNT  
Magna Mitral  
7000 / 7000TFX 
 
Carpentier-Edwards 
PERIMOUNT  
Magna Mitral Ease  
7200TFX 
 
Carpentier-Edwards PERIMOUNT 
Magna Mitral Ease  
7300 / 7300TFX 
 
 
Valve 
Carpentier-Edwards 
PERIMOUNT Magna Mitral 
pericardial bioprosthesis, 
model 7000TFX 
sizes 25 – 33 mm 
Valve is identical to the model 
7000TFX Valve, but has a 
different sizing convention; 
sizes 27 – 35 
Valve is identical to the model 
7000TFX valve, sizes 25 – 33 mm. 
A black silk suture guide line is 
added to the sewing ring 
Clip 
Acetal Homopolymer 
Acetal Homopolymer 
Acetal Homopolymer 
Clip contains new features for 
sleeve engagement and blue 
arrow molded into material. 
Jar 
3.8 oz Jar 
 
3.8 oz Jar 
 
3.8 oz Ribbed Jar 
Internal Ribs added to 3.8 oz Jar 
Sleeve 
Polypropylene Sleeve 
 
Polypropylene Sleeve 
 
Polypropylene Ribbed Sleeve 
External Ribs added to Sleeve 
Holder 
System 
 
 
Tricentrix Holder System: 
White* Holder  
White Post  
White Adapter  
 
*White also referred to as Natural  
Grey Tricentrix Holder System: 
Grey Holder  
Grey Post  
White Adapter  
Tri-color Tricentrix Holder System:  
Grey Holder  
White Post Blue Adapter  
Component color changed to 
provide additional contrast 
Accessories 
Handle Class I 
Sizers Class IIa 
Tray Class I 
 
NB: TÜV SÜD 
Product 
Service GmbH 
CE 0123 
Handles 1111, 1117 
Sizer 1177HP 
Tray TRAY1177HP  
Flex Handle 1172 
Replica Sizer 1171R 
Barrel Sizer 1171B 
Tray SET 1171 
Flex Handle 1173 
Replica Sizer 1173R 
Barrel Sizer 1173B 
Tray SET 1173 
Updated graphics and size 
markings on sizers and tray 
 
5.2 
Pre-Clinical Studies 
Pre-clinical bench studies included sewing ring integrity testing, spot weld pull test and 
chromium-cobalt band compression resistance testing, valve hydrodynamic, durability 
and structural integrity testing, shelf life & packaging and biocompatibility testing.  All 
testing met acceptance criteria per ISO 5840 and FDA Heart Valve Guidance 1996. 
 

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- pg 25 of 80 - 
6.0  
STUDY PROCEDURES 
 
Edwards will provide the study sites with the post approval study clinical protocol, case 
report forms (CRFs) (Appendix 5), Quality of Life survey (Appendix 6) and all other 
necessary study related documentation.  Edwards’ Clinical Affairs Department or 
authorized designee will conduct all aspects of data quality assurance (data monitoring, 
and monitoring of study sites) per departmental Standard Operating Procedures. 
 
Each study site will adhere to all the requirements specified in this protocol.  
Assessments will be obtained for the preoperative and operative visits, and 
postoperatively at discharge, six months, 1-year and annually thereafter for a minimum 
of 8 years (see Tables 4, 5, 6 and 7).   
 
The investigator will make every attempt to follow the subjects and will document the 
information gathered during the required study follow-up visits on the standardized 
CRFs.  The subjects will be encouraged by the investigator to report any address or 
telephone number changes.  They will also be informed of the importance of returning 
for scheduled follow-up visits even if they are not having any problems.   
 
Each site will provide a list of normal blood values and a certificate, or equivalent 
documentation, outlining the quality level of their laboratory prior to study initiation. 
 
6.1 
Preoperative Procedures 
 
All procedures shall be documented on the applicable visit case report forms (see 
Appendix 5). Compact discs or electronic copies of Doppler echocardiographic 
examinations will be sent directly to the Core Laboratory according to the procedures 
outlined in Appendix 3 - Echo Core Lab Protocol.  A summary of all required treatment 
procedures can be found in Table - Study Schedule.  
 

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- pg 26 of 80 - 
Table 5: Pre- Operative Evaluations and Data Requirements 
 
Patient Status 
Date of birth, gender, demographics 
Physical Assessment 
Height, Weight, Heart Rate, Blood Pressure, 
NYHA classification 
Medical History 
Non cardiac conditions, cardiac conditions, 
previous cardiac surgery  
Electrocardiogram  
Cardiac Rhythm 
Blood studies 1  
RBC, WBC, HCT, Plasma Free HGB, (or 
Haptoglobin and SLDH) Platelet and 
Reticulocyte counts 
Pregnancy Test 
Blood or Urine 
Medication Use 
Antiplatelet, Antithrombolytic Therapies 
Coagulation Profile  
PTT or INR  
Echocardiography 2 
Exam Date/Interval 
Echo Core Lab  
Cardiac output, Ejection fraction, Peak and 
mean valve gradients, assessment of stenosis 
or regurgitation, LV structure and function, LV 
mass, jet velocities 
Quality of Life Survey 3 
EQ-5D  
 
 1  Pre-procedure blood studies to be performed within 30 days of the planned valve 
replacement procedure. 
 
2  Pre- procedure echocardiography to be performed within 6 months of the planned valve 
replacement procedure 
 
3 Quality of Life survey to be completed within 3 months of planned valve replacement 
procedure 
 
6.2 
Operative Procedures 
 
Investigators shall use routine surgical technique for mitral valve replacement surgery in 
accordance with the relevant IFUs and carefully following the valve sizing, and valve 

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- pg 27 of 80 - 
orientation Tricentrix valve holder system instructions, (See Appendix 4 for Instructions 
for Use).   
 
 
Required operative evaluations and data requirements are listed below in Table 6. An 
intra-operative transesophageal echo (TEE) is not required for this study, however if an 
echo is performed, the investigator should send a copy of the examination to the Echo 
Core Lab for evaluation.   
 
Table 6: Operative Evaluations and Data Requirements 
 
Valve Implant Procedure  
Implant date, implanting surgeon name 
Valvular Lesion Assessment 
Diagnosis for valve replacement, current 
condition of valve, condition of annulus, 
(debridement procedures) condition of leaflets 
and preservation of subvalvular apparatus  
Study Valve Implant Data 
Valve size, model and serial number, bypass 
pump time, total cross clamp time, suture 
technique, use of pledgets, valve seating leaflet 
coaptation 
Surgical Approach 
Full or mini-sternotomy 
Concomitant Procedures 
CABG, AVR, tricuspid repair, etc. 
Echocardiography 
TEE is optional, If TEE is performed, site shall 
send to exam to Core Lab for evaluation  
Adverse Events 
All adverse events or complications regardless 
of relationship to the device or valve 
replacement procedure 
 
6.3 
Postoperative Procedures 
6.1.1  Hospital Discharge  
 
 Prior to hospital discharge, the investigator or designee will provide the study 
subject with an Implant Data Card (See Section 10.8 and Appendix 7).   

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The Investigator or designee will explain the use and importance of the implant 
card and shall ensure that all required information (Investigator Name, Facility 
Name and contact information) has been included on the card.   The Investigator 
or designed shall also ensure that one of the valve serial number  serial number 
stickers provided with the implant packaging is firmly attached to the back side of 
the Implant Data Card.  The second implant serial number sticker should be 
placed either on the front page of the subject’s operations notes, or scanned into 
the subject’s hospital electronic records. 
 Hospital discharge evaluations and data requirements are listed in Table 7. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
        Table 7: Early Post-Operative / Discharge Procedures and Data Requirements 
(30 days or discharge, whichever is later)  
Patient Status 
Complete Implant Card 
Physical Assessment 
Heart Rate, Blood Pressure, NYHA 

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- pg 29 of 80 - 
classification 
Electrocardiogram  
Cardiac Rhythm 
Medication Use 
Antiplatelet, Antithrombolytic Therapies 
Coagulation Profile  
PTT or INR  
Echocardiography  
Exam Date/Interval, clinical evidence of PV 
leak or regurgitation 
Echo Core Lab  
Cardiac output, Ejection fraction, Peak and 
mean valve gradients, assessment of stenosis 
or regurgitation, LV structure and function, LV 
mass, jet velocities 
Adverse Events 
All adverse events or complications that have 
occurred since the valve replacement 
procedure 
 
 
 
6.1.2 Late Post-Operative Follow- Up   
 
Postoperative follow-up visits are required between 3-6-months, at one year, and 
annually thereafter for a minimum of 8 years.   Required evaluations and data 
requirements are listed below in Table 8.    
 
 
 
 
 
 
 
Table 8.  Late Post-Operative Procedures and Data Requirements 
 
Patient Status 
Visit Date, Type of Visit 

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Physical Assessment 
Heart Rate, Blood Pressure, NYHA 
classification 
Electrocardiogram  
Cardiac Rhythm 
Blood studies  
RBC, WBC, HCT, Plasma Free HGB (or 
Haptoglobin and SLDH), Platelet and 
Reticulocyte counts 
Medication Use 
Antiplatelet, Antithrombolytic Therapies 
Coagulation Profile  
PTT or INR  
Echocardiography 
 (6 mo, 1. 2, 4 6, and 8 year follow-up visits) 
Exam Date/Interval, clinical evidence of PV 
leak or regurgitation 
Echo Core Lab  
Cardiac output, Ejection fraction, Peak and 
mean valve gradients, assessment of stenosis 
or regurgitation, LV structure and function, LV 
mass, jet velocities 
Quality of Life Survey  
(6 month visit only)  
EQ-5D  
Adverse Events 
All adverse events or complications that have 
occurred since the last visit 
 
Echocardiography exams are required at the 6-month visit (between 3-6 months), 
and at 1, 2, 4, 6, and 8 year follow-ups (± 1 month).  A QOL survey (EQ-5D) will 
be completed for the 6-month follow-up visit.   
 
Use of anticoagulant therapy is recommended for two to three months post-
operatively except where contraindicated.  The appropriate anticoagulation 
therapy must be determined by the physician on an individual basis and based 
on current ACC/AHA guidelines.   
 
Clinical assessment of adverse events shall be conducted per revised STS 
guidelines (Appendix 1) and reported per the event classifications and definitions 
provided in Section 7.0 and Appendix 8 respectively.  
 

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- pg 31 of 80 - 
6.4 
Unscheduled Visits 
 
If a subject needs to be seen at other than a regularly scheduled follow-up visit for 
assessment of cardiac symptoms, all visit information shall be recorded on the 
appropriate follow-up visit CRF.  If blood studies are performed the investigator shall 
document these studies on the CRF.  Doppler/echocardiography performed at these 
visits is optional, however if performed, the investigator should send the echo exam to 
the Core Lab for evaluation.  
6.5  
Missed Visit  
 
If a subject cannot be reached for the follow-up visit and misses the scheduled visit, the 
visit will be recorded as a missed visit.  The study site shall document the efforts made 
to contact the study subject or the subject’s primary health care provider for each 
required follow-up visit.  
   
6.6 
Lost To Follow-Up  
 
 
A subject will be considered “lost to follow-up” and terminated from the study when all of 
the following criteria have been met: 
 
• 
Failure to complete two consecutive visits without due cause; and 
• 
Documentation of three unsuccessful attempts on three different days 
over a period of 3 months by the Investigator or his/her designee to 
contact the subject or next of kin; and 
• 
A letter from the Investigator to Edwards requesting subject removal from 
the study, and 
• 
Prior agreement of Edwards to remove the subject from the study. 
 

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6.7 
Time Periods for Completing Study Visits 
 
Follow-up visits are scheduled for appointed times after the date of the procedure.  It is 
important that this schedule be maintained as closely as possible for all study subjects.  
Edwards recognizes that subjects may not be able to return for all scheduled visits at 
precisely the date required, and therefore, a period of time in which each visit is allowed 
is described in Table 9 below.  Studies not completed within these windows will be 
considered missed visits.  Study visits should be scheduled as close to the early part of 
the visit time period as possible so that if it is necessary to cancel and reschedule the 
visit, the visit could still be conducted in the required time period. 
 
Table 9.  Schedule of Follow-up Visits and Time Periods 
Follow-up Visit 
Time Period 
Discharge/30 Days 
Day before or Day of Discharge or 30 days post 
implant (whichever is later) 
Early Postoperative 
3 - 6 months  
Late Postoperative 
12 months ± 1 month 
Late Postoperative 
Annually from procedure date ± 1 month 
 
 
6.8 
Valve Explants 
 
Every effort should be made to return the explanted valve(s), at autopsy or explantation 
to Edwards.  The explanted valve should be placed in a container with a suitable 
histological fixative such as 10% formalin or 2% glutaraldehyde immediately after 
excision and returned to Edwards.  Refrigeration is not necessary under these 
circumstances.  Contact Edwards Clinical Research for additional instructions.   
 
Any pertinent information, e.g. operative notes, autopsy report etc should be sent to 
Edwards.  All supporting data should be de-identified at the site to protect the privacy of 
the study subject. 

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- pg 33 of 80 - 
 
After the study valve is explanted, the subject will be followed for either an additional 30 
days to monitor for any new adverse events or until all study device related serious 
adverse events are resolved.  After that point the subject will be discontinued from the 
study.  No further evaluations and/or case report forms are needed after study exit.  Data 
from these subjects will be included in analysis 
 
6.9  
Deaths/Autopsy Reports 
 
All deaths that occur during study participation and deaths that occur 30 days post-study 
valve explantation shall be reported to the Edwards Clinical Affairs Department. The 
Investigator shall provide a written summary of the subject death including the cause of 
death and relationship of the death to the study valve or procedure. Copies of an 
autopsy report and/or death certificate shall be submitted to Edwards as permitted by 
local law.  Death notifications shall be de-identified in order to protect the privacy of the 
subject. 
6.10  Subject Withdrawal  
 
Although all subjects are informed of their right to withdraw from the clinical study at any 
time, it is anticipated that such withdrawals will be infrequent.  All measures should be 
taken by the Investigator and their staff to encourage subjects to return for required 
follow-up visits.  The clinical study objective may be jeopardized if large numbers of 
subjects are lost to follow-up. 
 
All subjects are expected to continue in the study until Edwards notifies the Investigator, 
in writing that further follow-up is no longer required, except in the event of death or upon 
the subject’s written request for early withdrawal from the clinical study. A copy of any 
request for subject withdrawal shall should sent to Edwards via the study monitor and a 
Subject Withdrawal case report form completed.  

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- pg 34 of 80 - 
Table 10.  Study Schedule 
Time Period  
 
Data Collection  
Pre-
Operative 
Operative 
 
Early Post-
Operative 
/Hospital  
Discharge  
 
Late  
Postoperative 
(3-6 Months) 
1 Year 
 (11-13 
months)  
Annually   
Unscheduled 
Visit 
Informed Consent 
X 
 
 
 
 
 
Study Eligibility 
X 
 
 
 
 
 
Patient Status 
X 
 
X 
X 
X 
 
Physical Assessment  
X 
 
X 
X 
X 
 
Electrocardiogram 
X 
 
X 
 
X 
 
Blood Studies 
X 
 
 
X 
X 
 
Pregnancy Test 
X 
 
 
 
 
 
Medication Use 
X 
 
X 
X 
X 
 
Coagulation Profile 
X 
 
X 
X 
X 
 
Echocardiography 
X 
 
X 
X 2 
X 2 
X 3 
Quality of Life Survey 
(EQ-5D) 
X 1 
 
 
X 1 
 
 
Implant Procedure 
 
X 
 
 
 
 
Concomitant 
Procedures 
 
X 
 
 
 
 
Adverse Events 
 
X 
X 
X 
X 
X 
 
1  QOL surveys are required pre-operatively and at the 3-6 month visit.  
2  Echocardiograms are required at 6 months, 1 year, 2, 4, 6 and 8 year follow- up visits. 
3  If blood studies or echocardiograms performed at unscheduled visits, they should be recorded on the 
appropriate CRF, Echo data should be submitted to the Core Lab for evaluation.  
 
6.11 Core Laboratory 
Independent Core Laboratory evaluation of all Doppler echocardiograms will be 
performed using common protocols and CRFs.  The purpose of a Core Laboratory is to 
ensure unbiased, timely and consistent analysis of this diagnostic data.  A Core Lab is 
responsible for evaluating changes in study subject status over the course of the study 
based on serial studies in the same study subject.  Core Lab personnel shall be qualified 

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- pg 35 of 80 - 
by training and experience in Doppler echocardiography data analysis. Edwards will 
ensure that Core Lab personnel are familiar with the study valve.  Edwards or its 
designee will monitor Core Labs periodically to ensure adherence to data review 
schedules.  Clinical Affairs will also perform audits of  Core Labs at least once per year 
to ensure compliance with applicable study requirements   
 
Doppler Echocardiograms 
Echocardiographic studies shall be performed per the Core Lab Protocol found in 
Appendix 3.  Sites shall send properly labeled compact discs or electronic copies of 
echocardiograms directly from the Study Sites to the Core Lab. The Core Laboratory will 
review the echocardiograms upon receipt and notify the Edwards promptly if the exam is 
of insufficient quality for analysis.  Edwards will contact the site and request additional 
echocardiograms for analysis. 
 
7.0  
ADVERSE EVENTS 
 
An adverse event has been defined as any side effect, complication or medical consequence 
that has adverse health implications for the study subject receiving the study product/ treatment. 
Adverse events may be considered anticipated or unanticipated and shall be classified per the 
applicable definitions for the countries in which the study is being conducted.  
 
The Investigator at each participating center is responsible for reporting adverse events 
(complications) to the Edwards or its designee regardless of whether they are considered to be 
related to the study procedure or study device.  The Investigator shall complete the appropriate 
adverse event case report forms (See CRFs in Attachment 5) at each study visit, indicating the  
relationship of the event to the study device or procedure. The adverse event CRF for a given 
visit must report all adverse events that have occurred since the last documented visit.  For 
example, all adverse events occurring after the Discharge visit, but prior to the 3-6 months 
postoperative visit should be reported on the 6 month follow-up CRF. 
 

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Anticipated Adverse Events 
A variety of device and procedure related complications are expected to occur in 
subjects undergoing mitral valve replacement  These predefined complications are 
considered adverse events. (See Appendix 8 for definitions of anticipated adverse 
events).  
 
Unanticipated Adverse Device Effect (US CFR 21-812.3 ) 
An unanticipated adverse device effect is defined as “Any serious adverse effect on 
health or safety or any life-threatening problem or death caused by, or associated with, a 
device, if that effect, problem, or death was not previously identified in nature, severity, 
or degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious problem 
associated with a device that relates to the rights, safety, or welfare of subjects.    
 
NOTE: By definition a UADE is considered Serious, therefore for the purposes of 
reporting at European sites under ISO 14155, all UADEs should be reported as 
Serious Adverse Device Effects (SADEs).  
 
This study will also report adverse events from non-US sites under the following 
additional classifications:  
 
Adverse Device Effect (ADE): (ISO14155-1:2009) 
An Adverse Device Effect is defined per ISO 14155 as “Any untoward and unintended 
response to a medical device”, including events that result from insufficiencies or 
inadequacies in the Instructions for Use, the deployment of the device, as a result of 
user error. Both the study subject or user may experience an adverse device effect if the 
event is due to user error. (Meddev 2.12) 
 
 
 

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Serious Adverse Event (SAE): (ISO 14155-1:2009) 
An serious adverse event is defined as an event that:  
a) 
led to death 
b) 
led to a serious deterioration in the health of a subject that  
1) 
resulted in a life-threatening illness or injury,  
2) 
resulted in a permanent impairment of a body structure or a body 
 
function,  
3) 
required in-patient hospitalization or prolongation of existing 
 
hospitalization, or  
4) 
resulted in-patient medical or surgical intervention to prevent permanent 
 
impairment to body structure or a body function 
c) 
led to fetal distress, fetal death or a congenital abnormality or birth defect.   
 
Serious Adverse Device Effect (SADE): (ISO 14155-1:2009) 
As Serious Adverse Device Effect is defined as an “adverse device effect that has 
resulted in any of the consequences characteristic of a Serious Adverse Event or that 
might have led to any of these consequences if suitable action had not been taken or 
intervention had not been made or if circumstances had been less opportune”.   
 
7.1 
Adverse Event Reports 
 
All adverse events regardless of device relationship shall be recorded and reported to 
Edwards Lifesciences.   
 
Adverse events related to the study device, unanticipated adverse device effects 
(UADEs) and serious adverse events (SAEs) or adverse device effects (SADEs) 
must be reported to Edwards within 2 business days of knowledge of the event.    
 

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Following initial notification, the Investigator shall submit a written summary of the event 
(including the time and date of onset, complete description of the event, severity, 
duration, actions taken and outcome) to the Heart Valve Therapy Clinical Research 
department either via email to HVTClinicalResearch@edwards.com
 
, or by fax to +1-949-
809-5610 and to the reviewing IRB or Ethics Committee.  
Edwards shall report the event to the appropriate regulatory authorities per country 
specific regulations and respective adverse event classifications.  
7.2 
Medical Device Reporting (MDR) 
 
Edwards will be responsible for reporting events to the Food and Drug Administration in 
accordance with 21 CFR 803 Medical Device Reporting.  Examples of MDR events 
include the Safety Endpoints listed in section 3.3 above.  
 
7.3 
Medical Device Reporting Outside the United States 
 
Edwards will be responsible for reporting events to the Country Competent Authorities 
and EU Notified Bodies in accordance with MedDev 2.7.1 Dec 2009. Guidelines on 
Medical Devices.    
 
8.0   RISK ANALYSIS  
 
The purpose of this study is to confirm reasonable safety and effectiveness for the use of the 
Magna Mitral valve when compared to the Objective Performance Criteria from Annex R, Table R.1 
per ISO 5840 as proposed by the US FDA in the Heart Valve Guidance draft 2009.  

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8.1 
Potential Risks 
 
Risks known to be associated with the use of bioprothestic heart valves and valve 
replacement  procedures may include, but are not limited to the following: angina,  
cardiac 
arrhythmia, 
endocarditis, 
heart failure, 
hemolysis, 
hemolytic 
anemia, 
hemorrhage (bleeding), local and/or systemic infection, myocardial infarction, prothetic 
leaflet entrapment, prosthetic nonstructural dysfunction, prosthetic pannus, prosthesis 
perivalvular leak, prosthetic regurgitation, prosthetic structural deterioration, prosthesis 
thrombosis, thromboembolism, multi-system organ failure, non-cerebral blood clot, 
pericardial effusion or cardiac tamponade, respiratory failure, stroke or transient 
ischemic attack  
 
Additional risks associated with the use of Carpentier-Edwards PERIMOUNT mitral 
valve models have been compiled from critical literature reviews and from reports 
received through the Edwards Lifesciences complaint handling system. These risks may 
include but are not limited to the following: 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.  
As a result of these complications, a study subject may require: 
• 
reoperation or  
• 
explant and replacement of the Edwards Magna Mitral valve,   
OR may experience: 
• 
permanent disability 
• 
death    

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Although the Magna Mitral valve models have undergone extensive bench top and 
animal testing in accordance with the FDA guidance document, not all models required 
clinical trial data due to minor modifications.  
 
8.2 
Minimization of Risks 
 
Potential study subjects will undergo thorough preoperative assessments and only 
subjects who meet the study eligibility criteria will be allowed to participate in the study. 
Subjects will be closely followed intraoperatively and carefully monitored in the early 
post-operative period through hospital discharge.  Study subjects will undergo regular 
clinical examinations including serial blood studies to assess for hemolysis and anemia,  
and Doppler echocardiography examinations to assess hemodyamic performance of the 
valve throughout the duration of the study.  
 
The study devices were developed, designed and manufactured under an ISO compliant 
quality system and in accordance with applicable guidelines and international standards 
including the ISO14971 Medical Design Risk Management process. The biocompatibility 
of all components of the valve has been established in compliance with international 
standards (ISO10993-1), and designed to provide hemodynamic performance similar to 
other commercially available valves.  The sewing ring has been designed to facilitate 
sewing to and seating in the mitral annulus and valve materials have been selected for 
their durability and resistance to wear and fatigue.     
 
The study device should be used with caution in the presence of severe systemic 
hypertension or when the anticipated subject longevity is longer than the known 
longevity of the prosthesis.  Subjects undergoing dental procedures should receive 
prophylactic antibiotic therapy to minimize the possibility of prosthetic infection. 
8.2.1 Physician Training 
 

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Each investigator will have received appropriate product training in the study 
protocol and investigational plan requirements by the sponsor or sponsor 
representative. 
 
Data from all study sites will be monitored as it is submitted to Edwards.  
Qualified employees of Edwards, or a designated contract research organization 
(CRO), under contract with Edwards will conduct monitoring visits at the initiation 
of the study, periodically during the course of the study and upon study 
completion to assess ongoing compliance with the study protocol and adherence 
to protocol requirements.   
8.2.2 Clinical Events Review Committee  
 
A Clinical Events Committee (CEC) will be responsible for the ongoing review of 
all reported adverse events and will serve to adjudicate the relationship of the 
event and the study device or surgical procedure. The CEC will be composed of 
independent physicians familiar with the treatment of valvular heart disease and 
cardiac surgery and a statistician will evaluate the rates of complications, 
including deaths and explants for all subjects in the study as well as the 
hemodynamic performance of the Magna Mitral valve.  The CEC will be tasked 
with identifying any issues such as higher than expected complication and/or 
death rates or unanticipated adverse events or hemodynamic performance that is 
substantially better or worse than expected, to determine if the study should be 
stopped or changed at any time. 
 
8.2.3 Echocardiography Core Laboratory  
 
 
An Echo Core Lab will provide unbiased independent review of valve 
hemodynamics and potential valve complications over time.   

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8.2.4 Data Quality Assurance 
 
Edwards has designed quality assurance procedures to ensure that complete, 
accurate and timely data are collected, all Study Protocol requirements are 
followed and that all complications and adverse events are reported in a timely 
manner. 
 
Standardized case report forms (CRFs) will be used for the collection and 
recording of data at all study sites.  Investigators are responsible for the timely 
completion and submission of these forms to the Clinical Monitor. 
 
Incoming data are reviewed to identify inconsistent or missing data and adverse 
events.  Data problems will be addressed by telephone or written communication 
with the study sites and/or during site visits.  All hard copy forms and data files 
will be secured to ensure confidentiality. 
 
Pre-operative diagnostic tests will be evaluated by the Investigator and other 
appropriate professionals at the study sites to determine the study subject’s 
suitability for the clinical study.  
 
Investigators shall maintain all source documents required by regulation, 
including diagnostic test reports, laboratory results, completed case report forms, 
supporting medical records and informed consents.  The source documents will 
be referenced during regular monitoring visits to verify the information 
documented on the case report forms.   
8.3 
Potential Benefits 
 
In general, young patients, patients with chronic atrial fibrillation and who require long-
term anticoagulation and patients who wish to minimize the chance of re-operation 

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should chose a mechanical valve6.  Patients with implanted mechanical valves are 
generally considered to have a serious threat of thromboembolic adverse events thus 
requiring a lifelong anti-thromboembolic therapy.  Even with adequate anti-
thromboembolic therapy, the risk of adverse events is significant, particularly when the 
risk of serious hemorrhage is considered.  
 
For patients in whom anticoagulation therapy is contraindicated and for patients who are 
in sinus rhythm and who wish to avoid anticoagulation therapy, a bioprosthetic (tissue) 
valve is preferred6.  The ACC/AHA Guidelines for Management of Patients with Valvular 
Heart Disease states that it is reasonable to implant  a mitral bioprostheses in patients 
age 65 years and older with long standing atrial fibrillation. A mitral valve replacement 
may be also considered appropriate for patients less than 65 years of age who are in 
sinus rhythm with lifestyle considerations who have been informed of the risks of 
reoperation vs. anticoagulation.   
 
Bioprosthetic valves have the advantage of low thrombogenicity, which must be weighed 
against limited long term durability and subsequent hemodynamic deterioration and the 
risk of reoperation6. Hemodynamically, the bovine pericardial valves maximize use of the 
flow area and minimize flow resistance, thus providing a better solution to flow problems 
than the porcine valves.  The bovine pericardium has superior intrinsic properties to 
porcine aortic valve, notably in terms of collagen content20 and tolerance to high bending 
curvatures which can favorably influence the long-term mechanical durability of 
pericardial valves.   
 
Although the proven longevity of bioprostheses is not as long as that of some of the 
currently available mechanical valves, results from a multi-center study involving the 
original Carpentier-Edwards PERIMOUNT mitral valve model 6900 showed actuarial 
freedom from explant due to structural valve deterioration (SVD) to be 68.8% ± 4.7%.  
Results from the same study showed overall actuarial survival rate to be 37.1% ± 3.3% 
and valve related survival rate to be 63.1% ± 4.4% at 14 years.  Actuarial freedom from 

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adverse events at 14 years was as follows: thromboembolism, 83.8% ± 3.2% and 
hemorrhage, 86.6% ± 3.2%20.  Subjects participating in this study will be closely followed 
to monitor their health and safety. 
 
8.4 
Risk /Benefit Analysis 
 The Clinical Risk Assessment has been revise to consider the Model 7300/7300TFX.  
Please refer to Appendix 9 attached. 
 
 

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9.0 
STATISTICAL ANALYSIS 
 
Please refer to Sections 11.1 – 11.3 for study sample size calculations, and a summary of the 
study analysis plan . Sections 11.4 and 11.5 address the issues of data poolability and missing 
data.  Unless otherwise noted, all statistical tests will be performed at the α = 0.05 level. 
9.1 
Sample Size Calculation 
The sample size calculation for the trial is based on the primary safety endpoints.  The 
linearized rates for thromboembolism, all hemorrhage, all perivalvular leak, and 
endocarditis will be compared to the Objective Performance Criteria from Annex R, Table 
R.1 per ISO 5840 as proposed by the US FDA in the Heart Valve Guidance draft 2009.  
These OPC are presented in Table 11. 
 
Table 11: Safety OPC 
 
Adverse Event 
OPC 
Thromboembolism 
2.5 
All Hemorrhage 
1.4 
All Perivalvular Leak 
1.2 
Endocarditis 
1.2 
 
More specifically, a statistical test based on the Poisson distribution will be performed 
for each of these adverse event rates to evaluate whether it is less than 2 times the 
appropriate OPC.  Thus, the null and alternative hypotheses for each adverse event 
are as follows: 
H0: λ ≥ 2·OPC 
HA: λ < 2·OPC 

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where λ is the linearized rate for the given adverse event (thromboembolism, valve thrombosis, 
all hemorrhage, all perivalvular leak, and endocarditis) computed when the total subject years 
reaches 808 and OPC denotes the relevant OPC.  The test statistic for each adverse event is of 
the form: 
(
)
λ
λ
OPC
Z
⋅
−
=
2
. 
H0 is rejected in favor of HA if Z is less than -1.645, the lower 5% percentile of the standard 
normal distribution.  Grunkemeier, et al.32 have demonstrated that 800 subject life-years is 
adequate to test against the smallest OPC of 1.2% per subject year (excluding valve 
thrombosis, and stratification for major versus minor hemorrhage, and perivalvular leak) with 
Type I and Type II error controlled at the .05 and .20 levels, respectively.   
The proposed subject enrollment is calculated to ensure that at least 101 subjects survive to 8 
years post implant.  These 8*101 = 808 life years in addition to the life years from those 
subjects not surviving to 8 years will more than fulfill the 800 life-years required by Grunkemeier, 
et al.32. 
Sample size calculation for primary effectiveness endpoint is based on a test of the hypothesis: 
H0: p ≤ 75% 
HA: p > 75% 
where p is the proportion of the subjects in NYHA Class I or Class II at 8 years post implant. 
The expected proportion of the alive subjects in NYHA class I or II at eight years is 
approximately 90%, based on 7 year follow up data for the Carpentier-Edwards PERIMOUNT 
6900/6900P valve (this proportion is essentially constant across each annual visit).  Based on 
this expected proportion, a sample size of 45 subjects provides 85% power to test the 
hypothesis that the true proportion is greater than 75% using an exact binomial test.  Thus, the 
sample size of 101 subjects with NYHA data at 8 year post implant is more than adequate to 
provide sufficient power. 

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The calculated number of subjects (n) that must be enrolled in order to have 101 subjects 
survive to 8 years post implant with 99% probability is based on the binomial distribution.  
Specifically, n is such that 
(
)
%
7.
98
1
1
101
1
>
−






−
−
=∑
x
n
x
x
p
p
x
n
 
where p is the probability that a subject will survive for 8 years post implant.  This calculation 
can be performed using standard statistical software.  Based on the reported 8-year survival of 
56% from Thourani, et al. 33, a sample size of 212 subjects fulfills the requirements of the 
equation above.  Based on the data collected in a previous post approval study conducted by 
Edwards (Study 98-1), a lost to follow-up rate of 7.8% was observed among subjects who 
reached 5 or more years of follow-up post implant.  The sample size is further inflated to 250 to 
account for up to a 15% rate of lost to follow up.  
 
The STS Executive Summary indicated that 15% of patients undergoing mitral valve surgery in 
2007 in the United States underwent simultaneous mitral and aortic valve replacement 
(1205/7883) 5.  In order to reflect actual market use of the Carpentier-Edwards PERIMOUNT 
Magna Mitral valve, of the 250 subjects enrolled in the study, approximately 38 are anticipated 
to be those patients eligible for simultaneous aortic and mitral valve replacement.  
9.2 
Analysis Population 
All the data collected up to the point of the explant or expirations will be included in the 
safety and effectiveness analyses.  The primary safety analysis will include all the 
enrolled subjects.  The primary effectiveness analysis will include the subjects who 
survived and have NYHA assessment at 8 years post implant. 
 
9.3 
Safety Analysis 
 
 
9.3.1 Primary Safety Endpoint 
 
As described above a statistical test based on the Poisson distribution will be 
performed to investigate whether the linearized yearly rate for each 

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cardiovascular adverse event (thromboembolism, all hemorrhage, all perivalvular 
leak, and endocarditis) is less than 2 times the appropriate Objective Performance 
Criteria from Annex R, Table R.1 per ISO 5840 as proposed by the US FDA in the 
Heart Valve Guidance draft 2009.  
 
For reporting purposes, the percent of subjects who experience an early adverse 
events within 30 days of implant will be summarized.  Linearized rates will be 
used to summarize adverse events for the late (>30 days) post-operative period.  
The linearized rates will be reported as the number of events occurring after the 
early post-operative period per year of subject survival.  In addition, the linearized 
rate and 30-day frequency for thromboembolism will be stratified by concomitant 
cardiac problems (atrial fibrillation, sinus rhythm, pacemakers, etc.). 
 
Accounting for both early and late post-operative events, actuarial analysis 
according to Kaplan-Meier will be used to show estimated probability of freedom 
from each adverse event.   
 
9.4  
Secondary Safety Endpoints 
The analysis of secondary safety endpoints will be presented for the entire study 
cohort and also stratified by valve size according to the Tissue Annulus Diameter 
(TAD) and by valve model (7000/7000 TFX, 7200 and 7300/7300TFX). 
 
9.4.1 Blood Data 
Blood data (red blood count, white blood count, hematocrit, plasma free 
hemoglobin (or Haptoglobin and SLDH), reticulocyte and platelet counts) will be 
collected preoperatively, at 6-months and annually post implant.  This blood data 
will support the absence / presence of related adverse events; in particular 
hemolysis.  Data will be reported as the percent of subjects with results within the 
normal ranges at each time interval.  The percent of subjects with hemolysis at 

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- pg 49 of 80 - 
each point will also be reported.  Summaries will be presented for the entire 
study cohort and will also be stratified by valve size and valve model.    
 
9.4.2 Time to Death, Reoperation, and Explant 
Time to death from the date of operation will be analyzed by the method of 
Kaplan and Meier.  Time to reoperation from the date of operation as well as time 
to explant from the date of reoperation will be similarly analyzed.  For time to 
explant and time to reoperation, the time to first explant or reoperation will be 
calculated for those subjects requiring explant or reoperation.  These analyses 
will also be reported for the entire study cohort and also stratified by valve size 
and valve model.  Analyses for time to explant and time to reoperation will also 
be stratified by fatal versus non-fatal events.   
 
9.4.3 Nonstructural Valve Dysfunction and Structural Valve Deterioration 
The percentage of subjects experiencing nonstructural valve dysfunction and 
structural valve deterioration within the early post-operative period (within 30 
days of implant) will be reported.  Linearized rates will be used to summarize 
nonstructural valve dysfunction and structural valve deterioration for the late (>30 
days) post-operative period.  The linearized rates will be reported as the number 
of nonstructural valve dysfunctions and structural valve deteriorations occurring 
after the early post-operative period per year of subject exposure.  The 30-day 
frequency and linearized rate for nonstructural deterioration and structural 
dysfunction will be stratified by the nature of the dysfunction. These analyses will 
be reported for the entire study cohort and also stratified by valve size and valve 
model. 
9.5  
Effectiveness Analysis 
The effectiveness analyses will be reported for the entire study cohort and also 
stratified by valve size according to the Tissue Annulus Diameter (TAD) and 
valve model (7000/7000 TFX ,7200 and 7300/7300 TFX). 

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9.5.1 Subject Functional Classification 
 
Subjects will be stratified according to the NYHA classification preoperatively, at 
6 months and annually post implant for 8 years.  The distribution (numbers of 
subjects and percentages) in the various NYHA classes with be tabulated at 
each follow-up interval.  The percentage of the subjects in NYHA Classes I or II 
at 8 years post implant will be calculated to determine if it is ≥ 75% using a one -
sided Binomial exact test. This analysis will also be reported stratified by valve 
size and valve model. 
 
9.5.2 Hemodynamic Performance 
 
Echocardiography data will be obtained preoperatively, early postoperatively 
and/or discharge, at 6-months and at 1, 2, 4, 6 and 8 year follow-ups.  
Descriptive statistics for the continuous echo variables and change from baseline 
(e.g. mean, standard deviation, and range) will be categorized by time interval 
and valve size.  Regurgitation data will be summarized using frequency at each 
severity level by time interval and valve size.  Improvement in regurgitation at 
one year will be analyzed via the Jonckheere-Terpstra test34.  Change at one 
year from baseline for all other hemodynamic outcomes will be analyzed using 
paired t-tests. These analyses will also be reported for the entire study cohort 
and also stratified by valve model. 
 
9.6  
Poolability 
 
Subject baseline risk will be statistically compared between centers and regions 
(ie,. United States vs. Canada, United States vs. Europe, United States vs. Asia 
Pacific, and United States vs. Israel).  Chi-square tests will be used to compare 
categorical risk factors while analysis of variance will be used to compare 

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continuous risk factors.  Comparisons will be based on the following 
demographic and pre-operative variables: age, sex, etiology, previous heart 
valve replacement surgery, valvular lesion, pre-operative NYHA, concomitant 
cardiac procedures, and coexisting cardiovascular conditions.  Also included in 
the analysis will be the size of implant adjusted for both model 7000/7000TFX, 
model 7200TFX and models 7300/7300TFX according to the TAD.  Furthermore, 
time to event for the following events will be compared between centers via a log-
rank statistic: thromboembolism, all hemorrhage, death or explant, and death.  
Additional analyses may be performed if the need arises. 
9.7  
Missing Data 
 
All statistical tests on the effectiveness endpoints will be performed in two ways: (1) 
using only those subjects with available required for endpoint analysis and (2) by using 
the method of last observation carried forward (LOCF).  Both methods of analyses will 
then be compared.  However, both methods will be used for the comparison of NYHA 
classification at 8 year post implant to OPC (75%) and for the comparison of 
hemodynamic performance one year to baseline for the purpose of investigating the 
effect of loss-to-follow-up.   
 
NYHA classification and hemodynamic performance will be summarized at each of the 
follow-up interval.  In addition, the NYHA classification will only be statistically compared 
to OPC at 8 years post implant and only the one year post implant hemodynamic 
performance will be statistically compared to baseline. 
 
To further demonstrate the impact of lost of the follow-up on the effectiveness 
calculation; a bootstrapped simulation for missing data imputation will be generated as 
described below: 
For each subject who is alive and for whom NYHA assessment is not available at the 8 
year post implant follow up visit (Subject A), the last year for which NYHA data is 
available will be identified (year X). 

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Separately, a sub group (Group A) of subjects with the same pre-operative and year X 
NYHA information as Subject A, available data at 8 year post-implant will be identified. 
Subsequently, an observed value from the pool of subjects in sub group A will be 
selected randomly and used to impute the NYHA classification for subject A at 8 years 
post implant. 
The above steps (1-3) will be performed for each subject who is lost to follow up before 
the 8 year post implant follow-up visit. 
Lastly, steps 1 – 4 above will be repeated 999 times to generate 1000 estimated 
percentages of subjects with NYHA in classes I or II at 8 years post implant.  The central 
95th percentile for the 1000 estimated percentages will be calculated. 
The central 95th percentile generated by the simulation will reflect the variability in the 
primary effectiveness endpoint estimate caused by lost to follow up. 
10.0 ETHICAL AND REGULATORY CONSIDERATIONS 
 
The following must be observed in order to comply with the sponsor's policy for conduct and 
monitoring of clinical studies; they also represent sound research practice. 
10.1 Subject Informed Consent and Institutional Review Board/Ethical 
Review Committee 
A written subject informed consent form will be obtained preoperatively from all subjects.  
The subject must be adequately informed of his or her participation in the clinical study 
and what will be required of him or her in order to comply with the protocol requirements.  
In addition, a subject informed consent form is required to allow appropriate data 
collection and data monitoring including access to medical records by the sponsor and 
regulatory agencies (Appendix 2). 
 
If an Institutional Review Board (IRB) or Ethics Committee (EC) exists for an institution, 
this board/committee must approve the subject informed consent form and protocol for 
use at its institution.  If an IRB or EC does not exist, the head of surgery or medical 
director of the institution must approve the use of the subject informed consent form and 
protocol.  A written statement by the IRB/ERC or head of surgery / medical director 

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- pg 53 of 80 - 
indicating approval of the subject informed consent form and protocol must be submitted 
to the sponsor prior to study initiation. 
10.2  Health Economic Information 
 
In the United States only, the Sponsor may choose to obtain billing information such as 
charges associated with the ICU and hospital stays to evaluate hospital costs for the 
initial implant hospitalization and subsequent readmissions, as necessary.  For each 
subject, hospital charge data will be obtained from form UB-04 or similar report provided 
by the hospital. 
 
10.3 Case Report Forms (CRFs) 
 
Case report forms (CRFs) for individual subjects will be provided by Edwards (Appendix 
5).  The principal investigator or designee must keep a separate log of subject names 
and current addresses to facilitate record keeping and his or her ability to contact 
subjects for future follow-up. 
 
Stadardized CRFs will be used to record all study data. All data should be recorded 
accurately and completely.  Paper CRFs should be filled out using a blue or black ball 
point pen, and all handwritten comments must be legible for monitoring review and data 
entry purposes. Errors should be corrected by drawing a single line through the 
erroneous data, and recording the correction next to the data field.  All corrections must 
be initialed and dated by the person who makes the change.   Copies of the changed 
paper form must be provided to the sponsor and retained in the subject study file.  
 
Electronic data capture (EDC) may be used for part or all of the data collection in this 
study.  Edwards will provide training in the use of EDC to all necessary site personnel.  
Each investigator and staff participant will be assigned a unique password and only that 
individual should access subject records under that password.  Changes made to the 

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- pg 54 of 80 - 
electronic record after a report has been saved as completed will be tracked in an 
electronic audit file linked to the date the change was made and the password of the 
individual who opened the record.  Regardless of the type of CRF used, the sponsor will 
monitor subject CRFs for agreement with source documents on an ongoing basis. 
 
CRFs must be kept current to reflect subject status at each phase during the course of 
the study.  Instructions for CRF collection or submission are provided in the CRF 
synopsis. 
 
Completed CRFs must be signed by the principal investigator, co-investigator or his or 
her designee as listed in the Designation of Authority form for each subject receiving a 
study valve.   
Source data (including originals or copies of pre-operative assessments, operative 
records, reports, postoperative examinations, laboratory and other test results) shall be 
retained at the study center and shall be made available for inspection by the study 
sponsor, the study monitor, and authorized regulatory bodies upon request.  
Source data shall be de-identified in order to protect the privacy of the study subject and 
comply with HIPAA regulations in the US and European data protection laws.  
10.4 Study Termination 
 
The principal investigator will be notified in writing upon termination of the study. 
Edwards retains the right to suspend or terminate this clinical study at any time. 
10. 5 Record Retention 
 
Study files must be maintained at the clinical site for a minimum of two years after the 
study is either completed or terminated or until Edwards notifies the investigator that the 
records may be destroyed. 
 

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- pg 55 of 80 - 
10.6  Study Responsibilities 
 
10.6.1  Investigator Responsibilities 
 
The principal investigator is responsible for obtaining IRB/Ethics Committee 
approval for the study at his or her institution. 
 
Study records including CRFs, signed Agreement, originals of all blood and 
hemodynamic studies, signed subject informed consent forms, a copy of the 
implant data card, IRB/Ethics Committee approval letters, the log of IRB/Ethics 
Committee submissions, and other documents pertaining to the conduct of the 
study must be kept on file by the investigator. 
 
The investigator(s) will adhere to the regulations that provide the greatest 
protection to the subject. The investigator is responsible to comply with the 
following regulations: 
• 
US Code of Federal Regulations 
• 
21 CFR part 50: Protection of Human Subjects 
• 
21 CFR part 54: Financial Disclosure 
• 
21 CFR part 56: Institutional Review Boards 
• 
21 CFR part 814, subpart E: Post Approval Requirements 
• 
US Department of Health and Human Services: Health Insurance 
Portability and Accountability Act of 1996 (HIPAA) 
  
In Europe, study sites are responsible for complying with all applicable 
regulations including:  
• 
EU Medical Device Vigilance System 
• 
Declaration of Helsinki 
• 
Local and Regional Privacy Laws 

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- pg 56 of 80 - 
• 
Local and Regional Laws of the Country including Data Protection and 
ISO 14155 parts 1 & 2: Clinical Investigation of Medical Devices in 
Human Subjects, where appropriate for commercially available products 
 
 
All protocol deviations must be fully documented and explained on the CRF. 
These include noncompliance related to inclusion/exclusion criteria, consent 
form, blood data, echo and follow-up visits. 
 
Although the risks to the subject are felt to be the same as those reported for 
other available bioprostheses, the subjects receiving the Magna Mitral valves will 
be closely followed.  Any unusual or unanticipated adverse events will be 
reported immediately to the sponsor (see section 9.2) and if applicable, to the 
IRB/Ethics Committee as outlined in the Investigator's Statement and Agreement.  
If deemed necessary by the investigator, the IRB/Ethics Committee or the 
sponsor, the study may be suspended pending a thorough study of the incident. 
 
If the investigator wishes to assign the files to someone else or remove them to 
another location, he or she should consult with the sponsor in writing as to this 
change.  If there is a change or addition of co-investigator, an amended 
agreement must be completed promptly.  Any other personnel changes must be 
reported immediately to the monitor and a training program scheduled. 
 
Monitoring visits will be scheduled throughout the course of the study.  It is 
essential that the investigator set aside a sufficient amount of time for these visits 
to permit an adequate review of the study's progress, completed CRFs and 
original records. 
 
 
 

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10.6.2  Study Monitor/Sponsor Responsibilities 
 
A study monitor assigned to the study by the sponsor will monitor the progress of 
the study.  The study monitor must be acquainted with the investigator and other 
key individuals involved in the study.  The study monitor will remain in close 
contact with the site throughout the duration of the study to answer any questions 
and provide any needed materials, e.g. CRFs. 
 
The study monitor will be responsible for monitoring CRFs and visiting the site 
periodically to monitor study progress and compliance with the study protocol.  
Monitoring visits will be scheduled throughout the duration of the study at a 
mutually convenient time for the monitor and principal investigator or designee.  
 
The sponsor will provide results of the ongoing study to the Food and Drug 
Administration, including a comparison to the available data in the heart valve 
literature regarding other FDA-approved bioprosthetic valves implanted in the 
mitral position.  An Interim Post-Approval Study Status Report will be submitted 
every 6 months during the first two years of the study and annually thereafter.  A 
Final Clinical Study Report will be prepared as early as 3 months after the last 
study subject completes follow-up. 
 
10.6.3 Clinical Monitor 
 
The clinical monitor(s) is responsible for the conduct and administration of this 
clinical study.  These responsibilities include maintaining regular contact with 
each study site and conducting on-site monitoring visits at each study site at 
least once per year to ensure compliance with this study protocol, to verify that 
accurate and complete data are being submitted in a timely manner and to verify 
that the study site facilities continue to be adequate.   
 

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- pg 58 of 80 - 
The primary contact for this study is: 
 
 
 
  
 
  
 
 
   
 
 
 
 
 
 
 
 
10. 7  Study Changes 
 
Changes in the protocol may be made only by written amendments submitted to and 
agreed upon by the Food and Drug Administration (FDA).  Following written approval of 
a protocol amendment by the FDA, the sponsor will submit the amended protocol and 
associated document to the IRB/Ethics Committee.  The above changes shall be 
implemented upon written approval by the respective IRB/Ethics Committee.  
Administrative changes may be communicated to the FDA and to the IRB/Ethics 
Committee via the Annual Report. 
10. 8  Implant Data Card 
 
After implantation, subjects will be given the Implant Data Card by the Investigator prior 
to discharge (See Section 8.3.1 and Appendix 7).  This identification card allows 
subjects to inform healthcare providers what type of implant they have when they seek 
care. 
 
 
    

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10.9  Study Publication 
 
Investigator shall submit to Edwards early drafts of all abstracts, manuscripts or 
presentations authored by investigator and collaborators based on data generated from 
the clinical study at least sixty days prior to submission of the abstract, manuscript for 
publication or presentation.  Edwards shall have the right to advise investigator 
regarding proprietary information which shall not be divulged or the patentability of any 
inventions disclosed in the manuscripts.  If requested by Edwards, investigator shall 
delay submission of manuscripts for publication up to ninety days to permit preparation 
and filing of related patent applications.  In addition, Edwards shall have the right to 
require that any publication concerning the work performed hereunder acknowledges 
Edwards' financial support. 
 
It is understood, however, that no press releases, literature, advertising, publicity, or 
written statements in connection with work under the Clinical Studies Agreement having 
or containing any reference to Edwards shall be made by the clinical site and/or the 
investigator without the prior written consent of Edwards.  The clinical site and the 
investigator reserve the right to acknowledge the source of sponsorship in response to 
any legitimate inquiry. 
 
Neither party will use the name of the other in any form of advertising or publicity without 
the written permission of the other party. 
 
 
 
 
 
 
 
 
 

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- pg 60 of 80 - 
 
 
11.0  REFERENCES 
 
1. 
Yoganathan AP et. al., Fluid Mechanics of Heart Valves.  Annual Review of Biomedical 
Engineering 2004; 6:331-362. 
 
2. 
Carpentier A. Cardiac Valve Surgery—the “French Correction”. Journal of Thoracic 
Cardiovascular Surgery 1983; 86:323-337. 
 
3. 
Olson LJ et. al., Surgical pathology of the mitral valve: a study of 712 cases spanning 21 
years.  Mayo Clin Proc. 1987; 62:22-34. 
4. 
Edward NR et. al., Mitral valve repair and replacement in northern New England. American 
Heart Journal 2003; 145(6): 1058-1062. 
 
5. 
Executive Summary STS 10 year Report, December 2007. 
 
6. 
Gudbjartsson T. et. al., Mechanical/Bioprosthetic mitral valve replacement.  In: Cohn LH 
eds. Cardiac Surgery in the Adult. New York: McGraw-Hill, 2003:951-986. 
 
7. 
Chikwe J et. al., The surgical management of mitral valve disease.  British Journal of 
Cardiology  2004; 11(1): 42-48. 
 
8. 
The American College of Cardiology/American Heart Association 2006 Guidelines for the 
Management of Study subjects with Valvular Heart Disease. 
 
9. 
Schaff H Vi , Suri R Mi . Multiple Valve Disease. Cohn Lh, ed. Cardiac Surgery in the Adult. 
New York: McGraw-Hill, 2008:1129-1158. 
 
10. Bortolotti U, Milano A, Testolin L, et al: Influence of type of prosthesis on late results after 
combined mitral-aortic valve replacement. Ann Thorac Surg 1991; 52:84. 
 
11. Brown PJ, Roberts CS, McIntosh CL, et al: Relation between choice of prostheses and late 
outcome in double-valve replacement. Ann Thorac Surg 1993; 55:631. 
 
12. Cohn LH. Et al., Tricuspid regurgitation secondary to mitral valve disease: when and how to 
repair. Journal of Thoracic Cardiovascular Surgery 1994; 9:237-241 
 
13. De VegaNG, et al., La annuloplastia selective regulable y permanente: una tecnica original 
para el tratamiento de la insufficienca tricuspide. Rev Esp Cardiolo 1972; 25: 555-62. 
 

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and may not be reproduced, used or disclosed without written permission from Edwards Lifesciences LLC. 
 
 
- pg 61 of 80 - 
14. McCarthy PM, Bhudia SK, Rajeswaran J, et al.  Tricuspid valve repair:  durability and risk 
factors for failure.  J Thorac Cardiovasc Surg. 2004; 127: 674-685 
 
15. Matsuyama K, Matsumoto M, Sugita T, et al.  Predicotrs of residual tricuspid regurgitation 
after mitral valve surgery.  Ann Thorac Surg. 2003; 75: 1826-1828. 
 
16. Duran CM, et al., Is tricuspid valve repair necessary? J Thorac Cardiovasc Surg. 1980; 80: 
849-860 
 
17. Dreyfus GD, Corbi PJ, Chan KM, Bahrami T.  Secondary tricuspid regurgitation or 
dilatation:  which should be the criteria for surgical repair?  Ann Thorac Surg 79:127-132.  
  
18. Guidelines on the management of valvular heart disease by the European Society of 
Cardiology, 2007. 
 
19. McCarthy PM, Bhudia SK, Rajeswaran J, et al.  Tricuspid valve repair:  durability and risk 
factors for failure.  J Thorac Cardiovasc Surg. 2004; 127: 674-685. 
 
 
20. Marchand MA et. al., Fifteen year experience with the mitral Carpentier-Edwards 
PERIMOUNT pericardial bioprostheses.  Ann Thoracic Surgery 2001; 71: S236-9. 
 
21. David TE et. al., Late results of heart valve replacement with the Hancock II bioprostheses.  
J.  Thorac Cardiovasc Surg 2001; 121:268-78. ARTICLES 
 
22. Myken PS et. al., Seventeen-year experience with the St. Jude Medical Biocor porcine 
bioprostheses.  The Journal of Heart Valve Disease 2005; 14: 486-492. ARTICLES  
 
 
 
23. Carpentier A. From valvular xenograft to valvular bioprostheses (1965-1977). Med. Instrum. 
1977; 11(2); 98-101. 
 
24. Carpentier A., et. al., Continuing improvements in valvular bioprostheses. J. Thorac. 
Cardiovasc. Surg. 1982; 83(1): 27-42. 
 
25. Bonow RO et. al., ACC/AHA 2006 Guidelines for the management of study subjects with 
valvular heart disease.  JACC 2006; Vol. 48, No. 3, e1-e148. 
 
26. Edmunds, LH, Jr. et al. Guidelines for reporting morbidity and mortality after cardiac 
valvular operations. J Thorac Cardiovasc Surg 1988; 96: 351-353. 
 
27.  Akins, CW et al. Guidelines for reporting mortality and morbidity after cardiac valve 
interventions. J Thorac Cardiovasc Surg 2008;135:732-738. 
 
28. Yoganathan, AP et al. In vitro hemodynamic characteristics of tissue bioprostheses in the 
aortic position. J. Thorac Cardiovasc Surg 1986; 9212:198-209. 

Magna Mitral Post Approval Study Protocol 2006-05   
 
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and may not be reproduced, used or disclosed without written permission from Edwards Lifesciences LLC. 
 
 
- pg 62 of 80 - 
 
29. Liao K et. al., Bovine Pericardium versus porcine aortic valve: comparison of tissue 
biological  properties as prosthetic valves.  Artificial Organs 1992; 16(4) 261-365. 
 
30. Vesely I et. al., Comparison of the compressive buckling of porcine aortic valve cusps and 
bovine pericardium.  The Journal of Heart Valve Disease 1998; 7:34-39. 
 
31.  FDA 1994 draft Replacement Heart Valve Guidance 
 
32. Grunkemeier GL, et al., Sample size requirements for evaluating heart valves with constant 
risk events. The Journal of Heart Valve Disease 1994; 3:53-8 
 
33. Thourani VH et al., Outcomes and long-term survival for study subjects undergoing mitral 
valve repair versus replacement: effect of age and concomitant coronary artery bypass 
grafting. Circulation 2003; 108:298-304 
 
34. Sprent P et al., Applied nonparametric statistical methods. Chapman & Hall / CRC. New 
York, New York 2001 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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- pg 63 of 80 - 
 
 
 
 
 
 
 
12.0  APPENDIX 1- STS GUIDELINES FOR REPORTING MORBIDITY AND 
MORTALITY AFTER CARDIAC VALVULAR OPERATIONS 
 

DOI: 10.1016/j.jtcvs.2007.12.002 
 2008;135:732-738 
J Thorac Cardiovasc Surg
and Bruce W. Lytle 
Eric G. Butchart, David H. Adams, David M. Shahian, Siegfried Hagl, John E. Mayer
H. Blackstone, Gary L. Grunkemeier, Johanna J.M. Takkenberg, Tirone E. David, 
Cary W. Akins, D. Craig Miller, Marko I. Turina, Nicholas T. Kouchoukos, Eugene
 
interventions
Guidelines for reporting mortality and morbidity after cardiac valve
 
http://jtcs.ctsnetjournals.org/cgi/content/full/135/4/732
located on the World Wide Web at: 
The online version of this article, along with updated information and services, is
2008 American Association for Thoracic Surgery 
Association for Thoracic Surgery and the Western Thoracic Surgical Association. Copyright © 
 is the official publication of the American
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Guidelines for reporting mortality and morbidity after
cardiac valve interventions
Cary W. Akins, MD,a D. Craig Miller, MD,a Marko I. Turina, MD,c Nicholas T. Kouchoukos, MD,b
Eugene H. Blackstone, MD,a Gary L. Grunkemeier, PhD,b Johanna J. M. Takkenberg, MD, PhD,c Tirone E. David, MD,a
Eric G. Butchart, MD,c David H. Adams, MD,b David M. Shahian, MD,b Siegfried Hagl, MD,c John E. Mayer, MD,b and
Bruce W. Lytle, MDa
S
ince the initial publication of ‘‘Guidelines for Reporting Morbidity and Mortal-
ity After Cardiac Valvular Operations’’ in 1988,1 followed by a revised version
in 1996,2 valvular heart surgery has evolved to include an enhanced under-
standing of patient- and disease-related factors affecting outcomes, increased numbers
of valve repairs, more operations performed for patients with minimal symptoms, new
prostheses, novel repair methods, and the emergence of percutaneous interventional
(catheter-based) valve repair and replacement. To adapt to this changing environment,
the Councils of the American Association for Thoracic Surgery, The Society of
Thoracic Surgeons, and The European Association for Cardio-Thoracic Surgery
have directed an Ad Hoc Liaison Committee for Standardizing Deﬁnitions of Pros-
thetic Heart Valve Morbidity to review current clinical practice to update and clarify
these reporting guidelines. The guidelines are intended to cover treatment of all four
cardiac valves in both adult and pediatric patients. Further, these guidelines apply uni-
formly, irrespective of whether the therapy was carried out as a conventional open
operation, as a minimally invasive (video-assisted or robotic) surgical procedure, or
with percutaneous interventional catheter techniques.
Purpose
These reporting guidelines are intended to facilitate analysis and reporting of clinical
results of various therapeutic approaches to diseased heart valves such that meaningful
comparisons can be made and inferences drawn from investigations of medical, surgi-
cal, and percutaneous interventional treatment of patients with valvular heart disease.
Early Mortality
Early mortality is to be reported as all-cause mortality at 30, 60, or 90 days and
depicted by actuarial estimates (with number remaining at risk and conﬁdence inter-
vals [CIs]) or as simple percentages, regardless of the patient’s location, be it home or
in a health care facility.
Definitions of Morbidity
Structural Valve Deterioration
Structural valve deterioration includes dysfunction or deterioration involving the
operated valve (exclusive of infection or thrombosis), as determined by reoperation,
autopsy, or clinical investigation. Clinical investigation should include periodic echo-
cardiographic surveillance. Substantially increased regurgitation or stenosis of the
From The American Association for Tho-
racic Surgery,a The Society of Thoracic Sur-
geons,b and the European Association for
Cardio-Thoracic Surgery.c
This article is being published concurrently
in The Annals of Thoracic Surgery and
the European Journal of Cardio-Thoracic
Surgery.
Received for publication Dec 11, 2007;
accepted for publication Dec 11, 2007.
Address for reprints: Cary W. Akins, MD,
Cardiac Surgery, Cox 648, Massachusetts
General Hospital, 55 Fruit St, Boston, MA
02114 (E-mail: cakins@partners.org).
J Thorac Cardiovasc Surg 2008;135:732-8
0022-5223/$34.00
Copyright  2008 by the American Associ-
ation for Thoracic Surgery, the European
Association for Cardio-Thoracic Surgery,
and the Society of Thoracic Surgeons
doi:10.1016/j.jtcvs.2007.12.002
Guidelines
732
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Abbreviation and Acronym
CI 5 conﬁdence interval
operated valve over time should be reported with quantitative
or semiquantitative methods. The term structural valve dete-
rioration refers to changes intrinsic to the valve, such as
wear, fracture, poppet escape, calciﬁcation, leaﬂet tear, stent
creep, and suture line disruption of components of a pros-
thetic valve; it also refers to new chordal rupture, leaﬂet dis-
ruption, or leaﬂet retraction of a repaired valve.
Nonstructural Dysfunction
Nonstructural dysfunction is any abnormality not intrinsic to
the valve itself that results in stenosis or regurgitation of the
operated valve or hemolysis. The term nonstructural dys-
function refers to problems (exclusive of thrombosis and in-
fection) that do not directly involve valve components yet
result in dysfunction of an operated valve, as diagnosed by
reoperation, autopsy, or clinical investigation. Examples of
nonstructural dysfunction include the following: entrapment
by pannus, tissue, or suture; paravalvular leak; inappropriate
sizing or positioning; residual leak or obstruction after valve
implantation or repair; and clinically important intravascular
hemolytic anemia. In addition, nonstructural dysfunction in-
cludesdevelopmentofaorticorpulmonicregurgitationasare-
sult of technical errors, dilatation of the sinotubular junction,
or dilatation of the valve annulus after either valve replace-
ment with stentless prostheses (eg, pulmonary autograft, aor-
tic allograft, and xenograft valves) or aortic valve-sparing
operations if the cusps are seen to be normal at reoperation,
autopsy, or clinical investigation. For percutaneous and trans-
apical approaches to aortic valve replacement or conventional
open aortic valve replacement, new onset of coronary ische-
mia from coronary ostial obstruction or paravalvular aortic re-
gurgitation is considered nonstructural dysfunction. More
than mild recurrent or residual mitral or tricuspidregurgitation
after surgical or percutaneous interventional valve procedures
(coronary sinus interventions, direct reparative methods, or
other methods aimed at achieving ventricular remodeling) is
nonstructural dysfunction, unless there is disruption of the
valve components themselves, which would then be struc-
tural deterioration.
Sudden or progressive dysfunction or deterioration of the
operated valve may be structural, nonstructural, or both, as
determined by reoperation, autopsy, or clinical investigation.
Valve Thrombosis
Valve thrombosis is any thrombus not caused by infection at-
tached to or near an operated valve that occludes part of the
blood ﬂow path, interferes with valve function, or is sufﬁ-
ciently large to warrant treatment. Valve thrombus found at
autopsy in a patient whose cause of death was not valve re-
lated or found at operation for an unrelated indication should
also be counted as valve thrombosis.
Embolism
Embolism is any embolic event that occurs in the absence of
infection after the immediate perioperative period. Embolism
may be manifested by a neurologic event or a noncerebral
embolic event.
A neurologic event includes any central, new neurologic
deﬁcit, whether temporary or permanent and whether focal
or global, that occurs after the patient emerges from anesthesia.
Stroke is a prolonged (.72 hours) or permanent neuro-
logic deﬁcit that is usually associated with abnormal results
of magnetic resonance imaging or computed tomographic
scans. Patients with minimal, atypical, or protean symptoms
that lead to radiographic imaging demonstrating an acute
ischemic event are considered to have sustained a stroke.
Transient ischemic attack is characterized by fully revers-
ible symptoms of short duration. If radiographic imaging
demonstrates an acute central neurologic lesion (‘‘cerebral in-
farction with transient symptoms’’), however, such patients
are reclassiﬁed as having sustained a stroke.
Multiple or repeated transient events occurring during
a short period (a burst or cluster) should be recorded as one
event for calculation of event rates, but documented as a clus-
ter. Rate calculations should be provided not only for all
embolic events but also separately for strokes, transient
ischemic attacks, and clusters.
Postoperative neurologic symptoms that mimic those of
a preoperatively documented neurologic event and that are
conﬁrmed radiographically to be consistent with the former
event are not counted as a new neurologic event. Central
neurologic events that are clearly related to aortic, internal ca-
rotid artery, or vertebral artery disease, such as acute throm-
botic occlusion, atheroembolism, or spontaneous arterial
dissection, are also not counted. Psychomotor deﬁcits found
by specialized testing are not considered neurologic events
related to operated valves. Patients who do not awaken or
who awaken after operation with a new stroke are not consid-
ered to have sustained valve-related neurologic events.
A noncerebral embolic event is an embolus documented
operatively, at autopsy, or clinically that produces signs or
symptoms attributable to complete or partial obstruction of
a peripheral artery. Intraoperative myocardial infarctions
are not counted. Postoperative myocardial infarction is also
not counted unless the infarction is caused by a coronary em-
bolus (as detected by operation, autopsy, or clinical imaging).
Emboli consisting of nonthrombotic material (eg, atheroscle-
rosis, myxoma) are not counted.
Bleeding Event
A bleeding event is any episode of major internal or external
bleeding that causes death, hospitalization, or permanent
Akins et al
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injury (eg, vision loss) or necessitates transfusion. Major
bleeding unexpectedly associated with minor trauma should
be reported as a bleeding event, but bleeding associated with
major trauma or a major operation should not. Bleeding
events are reported for all patients regardless of whether
they are taking anticoagulants or antiplatelet drugs. Although
total bleeding events must be reported, bleeding events can
also be reported separately for those who are taking anticoag-
ulants or antiplatelet agents and those who are not.
Antithrombotic Management
The method of initiating antithrombotic treatment during
hospitalization should be speciﬁed (eg, intravenous unfractio-
nated heparin, subcutaneous low-molecular-weight heparin,
antiplatelet agent). If oral anticoagulant therapy is instituted,
the following information should be speciﬁed: (1) speciﬁc
drug used (eg, warfarin sodium, acenocoumarol, phenprocou-
mon), (2) target international normalized ratio for each valve
position, (3) average achieved international normalized ratio,
(4) method of anticoagulation control (eg, physician or nurse
directed, patient home self-management), and (5) duration of
treatment for patients with bioprostheses. If antiplatelet drugs
are used, they should be speciﬁed.
If the patient has a valve thrombosis, embolism, or bleed-
ing event, the international normalized ratio associated with
that event should be reported, together with any antiplatelet
therapy.
Composite Thrombosis, Embolism, and Bleeding
The composite end point of thrombosis, embolism, and bleed-
ing includes occurrence of all events meeting the previously
stated deﬁnitions of valve thrombosis, embolism, and bleeding
event. Because thrombogenicity and intensity of anticoagula-
tion may be manifested by several separate complications,
this composite end point represents a more accurate overall
assessment of the total hazard of thrombogenicity and antico-
agulation.3
Operated Valve Endocarditis
Operated valve endocarditis is any infection involving
a valve on which an operation has been performed. The diag-
nosis of operated valvular endocarditis is based on one of the
following criteria: (1) reoperation with evidence of abscess,
paravalvular leak, pus, or vegetation conﬁrmed as secondary
to infection by histologic or bacteriologic studies; (2) autopsy
ﬁndings of abscess, pus, or vegetation involving a repaired or
replaced valve; or (3) in the absence of reoperation or au-
topsy, meeting of the Duke Criteria for endocarditis.4 Posi-
tive blood cultures are not required for the diagnosis of
operated valve endocarditis. Culture-negative endocarditis
should refer only to negative blood culture results and not
just the absence of any proof of infection. Morbidities asso-
ciated with active infection, such as valve thrombosis, throm-
botic embolus, bleeding event, or paravalvular leak, are
included under this category, but not counted in other cate-
gories of morbidity.
Reintervention
Reintervention is any surgical or percutaneous interventional
catheter procedure that repairs, otherwise alters or adjusts, or
replaces a previously implanted prosthesis or repaired valve.
In addition to surgical reoperations, enzymatic, balloon
dilatation, interventional manipulation, repositioning, or
retrieval, and other catheter-based interventions for valve-
related complications are also considered reinterventions. In-
dications for reintervention must be reported. Open surgical
and percutaneous catheter reinterventions should be listed
separately.
Valve-Related Mortality
Valve-related mortality is any death caused by structural
valve deterioration, nonstructural dysfunction, valve throm-
bosis, embolism, bleeding event, or operated valve endocar-
ditis; death related to reintervention on the operated valve; or
sudden, unexplained death. Deaths caused by heart failure in
patients with advanced myocardial disease and satisfactorily
functioning cardiac valves are not counted. Speciﬁc causes of
valve-related deaths should be reported.
Sudden, Unexplained Death
A sudden, unexplained death is one in which the cause of
death has not been determined by clinical investigation or
autopsy ﬁndings and the relationship to the operated valve
is undeﬁned. These deaths should be reported as a separate
category, but also included in valve-related mortality.
Cardiac Death
Cardiac death includes all deaths resulting from cardiac
causes. This category includes valve-related deaths, sudden
unexplained deaths, and deaths from non–valve-related car-
diac causes (eg, from heart failure, acute myocardial infarc-
tion, or documented arrhythmias).
All-Cause Mortality
All-cause mortality includes all deaths from any cause after
a valve intervention. Survival should be referenced to an
age- and sex-matched sample from the representative general
population being investigated whenever possible.
Permanent Valve-Related Impairment
Permanent valve-related impairment is any permanent neu-
rologic or other functional deﬁcit caused by structural valve
deterioration, nonstructural dysfunction, valve thrombosis,
embolism, bleeding event, operated valve endocarditis, or
reintervention.
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Major Adverse Valve-Related Event
Major adverse valve-related events include the following: (1)
valve-related mortality, (2) all valve-related morbidity, and
(3) need for new permanent pacemaker or deﬁbrillator within
14 days after the valve intervention.
Data Collection
Data collection and reporting for all treated valves should
include location (aortic, mitral, tricuspid, pulmonary, multi-
ple), treatment method (repair, replacement, percutaneous
catheter intervention), repair methods if valve preserved
(including type of annuloplasty ring, suture annuloplasty,
or coronary sinus cerclage), and, for valve replacement, pros-
thesis type (mechanical prosthesis, stented bovine pericardial
or porcine bioprosthesis, stentless xenograft bioprosthesis,
aortic or pulmonary allograft, pulmonary autograft). For
prostheses, including annuloplasty rings, manufacturer and
model should be reported. For allografts, method of preserva-
tion should be given. Manufacturer label size should be stated
for each valve location, type, and model; in addition, cali-
brated annulus size (or maximal dilatation balloon diameter
during preliminary balloon valvuloplasty and during valve
deployment in cases of percutaneous aortic valve replace-
ment) before valve implantation should also be reported.
Not only should the number of treated valves be listed, so
too should the number of patients who received them.
Additional Pertinent Material
In addition, the report should specify the following:
1. The patient population from which the study cohort
was selected, preferably according to CONSORT
(Consolidated Standards of Reporting Trials) recom-
mendations (see http://www.consort-statement.org).
Inclusive dates of operation and whether the series
was consecutive should be stated. Criteria used to se-
lect patients should be deﬁned and listed. If a subset of
the sample population is reported, the total number of
patients who underwent valve intervention during the
inclusive dates of the clinical investigation should be
reported.
2. The method used for follow-up. This includes type of
follow-up, which may be active (direct contact with
patients or their families by examination, telephone,
letter, or questionnaire) or passive (use of administra-
tive or government data not involving direct patient
contact). Mode of follow-up should be included,
whether prospective anniversary contact (although
periodic follow-up may be at intervals shorter or
longer than 1 year) or cross-sectional, whereby an
entire group of patients is followed up more or less
at the same calendar time despite their index proce-
dures having occurred at widely disparate times.
3. Percentages of patient-level responses from each
method should be given. In case of an anniversary-
type follow-up, frequency of follow-up inquiry should
be provided.
4. Total follow-up time (patient-years), mean (and SD) or
median (and quartiles) if the distribution of data is
skewed, and maximum years of follow-up should be
given. If the study involves multiple valve positions,
treatment methods, repair techniques, and prosthesis
types, total follow-up time for each should be reported
separately.
5. The time period (closing interval) required to com-
plete current follow-up should be given if the common
closing date method is not used. The closing interval,
in which the current status of all patients is determined,
should be as short as possible. Alternatively, the status
of all patients at their exact anniversary dates, or as of
the receipt of the ﬁrst response to a cross-sectional
inquiry, may be used as a common closing date.
6. Completeness of follow-up can be calculated as the
ratio of total observed person-time to potential per-
son-time of follow-up to the closing date of the study.5
Although follow-up to death (or explant in a valve-ori-
ented analysis) is 100% complete, because of deaths,
observable patient-years will be less than potential pa-
tient-years. A modiﬁcation can be made of Clark and
colleagues’ C statistic to account for this, which will
yield a somewhat higher percentage.6 To improve
statistical validity, every effort should be made to
achieve complete current follow-up for more than
90% of patients.
7. Percentage of autopsies and documented modes of
death should be reported.
Data Analysis and Reporting
The method of reporting data should facilitate comparison
between reports and support the conclusions, inferences,
and predictions made. Methods chosen to analyze the col-
lected data depend on the purpose of the report and availabil-
ity of analytic techniques. Methods used to collect and
analyze data should be summarized in the Methods section,
with references included or deﬁned in an appendix.
Percentages (Not Time Related)
Some morbid events occurring within a short time frame may
be reported as simple percentages, that is, the number of
events divided by the number of patients (eg, 30-, 60-, or
90-day mortality), as long as the status of all patients is
known. Percentages should be presented with CIs7 and may
be compared by Pearson’s c2 test or Fisher’s exact test.8
Logistic regression analysis9 is available for evaluating the si-
multaneous inﬂuence of several risk factors on a dichotomous
outcome variable (percentage) and is often used to establish
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a risk model, that is, a mathematical formula incorporating
such factors.
Time-Related Events
Valve-related events should be reported in a time-related
manner, with time of treatment designated as time zero. Ka-
plan–Meier10 or other life table techniques11 provide actuar-
ial estimates of morbid events, and these should be reported
with 1 or 2 SEs of the estimate (equivalent to 68% or 95%
CIs). Number of patients remaining at risk should be indi-
cated at appropriate intervals, and curves should use dashed
lines beyond time frames containing few patients, such as
10% of the initial cohort in a typical-size (hundreds, not thou-
sands, of patients) study. Although comparisons between
subsets of patients can be made, actuarial methods are not
predictive beyond the time of the last actuarial estimate and
cannot be adapted to multivariable analysis. These methods
are called nonparametric or distribution free because they
do not assume a particular statistical distribution or model.
Risk Factors
The Cox proportional hazards model12 produces a time-
dependent analysis of valve-related events and provides
a multivariable regression method to discriminate risk factors
associated with speciﬁc valve-related morbid events during
speciﬁc intervals. The Cox method is a semiparametric
(model partially speciﬁed) approach that makes no assump-
tion about the shape of the underlying hazard function, but
identiﬁes risk factors and estimates multipliers of the baseline
hazard. These multipliers are the relative risks (called hazard
ratios) associated with the risk factors. Several methods are
available for assessing the assumption of proportional haz-
ards.13 When such methods reject the hypothesis of propor-
tional hazards, one can be reasonably sure that the method
is inappropriate and alternatives to it are needed; if the hy-
pothesis is not rejected, one unfortunately has not learned
much, because these methods are sensitive to number of
events and tend to be conservative.
Results of a multivariable analysis should be accompanied
by a list of the variables considered and a tabular presentation
of the numeric results. When modeling event risk (by either
logistic or Cox regression), the amount of information avail-
able is based on number of events, not number of patients or
patient-years. Thus, it is important that a sufﬁcient number of
events occur to enable accurate estimates. A ‘‘rule of 10’’
events as the minimum per risk factor considered in the
model has been advocated for both logistic regression14
and Cox regression,15 although this minimum could be low-
ered a bit.16 In cases of few events per risk factor, resampling
techniques can be used to test model validity.
Temporal Pattern of Risk
A fully parametric method (model completely speciﬁed) of
calculating a hazard function of valve-related morbid events
deﬁnes the instantaneous risk of an event at any time after
treatment.17 20 Such methods permit univariable and multi-
variable analysis (including those speciﬁc to various time
frames, such as early vs long-term risk), provide predictive
information beyond the time of the last event, indicate
whether the risk is constant, and provide CIs. For example,
the hazard function for structural valve deterioration for bio-
prostheses is not constant across time, but increases with time
since insertion; a Weibull function that accommodates an
increasing hazard with time should be considered.21,22
Linearized rates
If the risk of an event is constant over time, there is a simple
method to calculate that rate. The linearized rate is calculated
as total number of observed events divided by total patient-
years of follow-up. It is often expressed as events per 100
patient-years (percent per year). These rates should be con-
sidered only approximate unless the hazard function for the
complication under study is constant during the entire inter-
val considered, which is often not true for complications after
a cardiac valve procedure. Linearized rates should be re-
ported with CIs, which can be based on the Poisson distribu-
tion23 or on likelihood ratio methods for comparing the
means of exponential distributions.11,23 Linearized rates
can be compared with the likelihood ratio test,19,20,24 a test
that is based on the F statistic,12,20 or within appropriate mul-
tivariable models.
Repeated events
Some valve-related events, such as thromboembolism and
bleeding, can occur repeatedly. Although estimating freedom
from any such event is meaningful, even more important is
enumerating all such events. Some of the previously men-
tioned methods have been devised or extended to consider re-
peated events in the same patient.17,25,26 A simple and widely
used approach uses linearized rates, as described previously, to
estimate the incidence of multiple events. These rates should
be considered only approximate unless the risk of recurrent
events is the same as for initial events (which is often not
the case). If it is not, a simple approach is to restart time
zero at each event occurrence.
Valve Outcome Versus Patient Outcome
Time-related events that estimate valve performance are
measured from time of treatment until time of patient death,
valve explantation, or censoring; however, patients are inter-
ested in learning what events they may encounter during the
remainder of their lives. Thus, patient outcome should be
measured starting at the time of treatment until death (or cen-
soring). Because patient death competes with event occur-
rence, it is important to make a clear distinction between
valve performance and patient outcome. Because the Ka-
plan–Meier method assumes patient immortality when esti-
mating cumulative freedom from events, it overestimates
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the actual probability of event occurrence for the patient (or
a particular patient population). To translate valve outcome
(valve performance) to patient outcome (risk of an adverse
event), the cumulative incidence method is recommended.
For assessment of valve prosthesis performance or durability
of repair, which focuses on the valve rather than the patient as
the unit of measure, Kaplan–Meier and related actuarial
methods are appropriate, rather than cumulative incidence
methods.27 The Kaplan–Meier method is usually used to es-
timate occurrence of valve-related events. This method is not
perfect, because it assumes independence between death and
the event of interest, which in most instances is not true. In-
verse probability weighting may correct for this to provide
a better estimate of true valve performance.28
Longitudinal Outcomes
Time-related events after valve replacement are assumed to
occur at an instant in time; however, many outcomes of im-
portance are conditions or processes that evolve with time,
such as return of regurgitation after valve repair, change in
New York Heart Association functional class (graded or or-
dinal outcomes), regression of ventricular mass (continuous
outcome), and use of warfarin sodium (binary outcome).29
Values for these outcomes are captured at discrete instances
in time (‘‘snapshots’’), which may be taken repeatedly at pro-
spectively speciﬁed follow-up intervals, cross-sectionally, or
opportunistically.
Snapshots are subject to many biases. If a condition
changes rapidly but snapshots are taken infrequently, aliasing
is introduced. If opportunistic follow-up occurs only when
symptoms recur, the prevalence of undesirable change may
be overestimated. Change is also related to precision of
measurements; for example, degree of mitral regurgitation
depends on systolic blood pressure and quality of the echo-
cardiogram. Of course, the entire series of assessments is
truncated by death or by removal of the valve of interest.
The challenge in analyzing longitudinal data is estimating
the average temporal pattern of outcome and its variability in
the group of patients. This average must account for sampling
challenges, censoring (truncation) by death, unequal number
of repeated measurements of the outcome per patient, vari-
ability in time among repeated measurements (such as serial
echocardiographic assessment at different intervals after treat-
ment), and the fact that sequential measurements obtained for
a given patient will be more correlated with themselves than
will measurements between individuals. Thus, these kinds
of data, methods of longitudinal data analysis have developed
rapidly during the last two decades.30 These methods include
mixed models, random and ﬁxed effects models, generalized
estimating equation approach, and hierarchic models (such as
currently used for The Society of Thoracic Surgeons National
Database risk assessment).31 33 Longitudinal data analysis of
a series of assessments is superior to analyzing only condition
at last follow-up. This methodology is also superior to dichot-
omizing outcomes and analyzing them with actuarial methods
as if they were events, such as freedom from grade 31 mitral
regurgitation after repair.
We acknowledge the invaluable assistance given by Cindy
VerColen of The American Association for Thoracic Surgery for
the organization of this review and development of this document.
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DOI: 10.1016/j.jtcvs.2007.12.002 
 2008;135:732-738 
J Thorac Cardiovasc Surg
and Bruce W. Lytle 
Eric G. Butchart, David H. Adams, David M. Shahian, Siegfried Hagl, John E. Mayer
H. Blackstone, Gary L. Grunkemeier, Johanna J.M. Takkenberg, Tirone E. David, 
Cary W. Akins, D. Craig Miller, Marko I. Turina, Nicholas T. Kouchoukos, Eugene
 
interventions
Guidelines for reporting mortality and morbidity after cardiac valve
 
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Magna Mitral Post Approval Study Protocol 2006-05   
 
 REV I  November 18, 2013  
 
 
 
 
 
 This document and the information contained herein is considered Proprietary and Confidential  
and may not be reproduced, used or disclosed without written permission from Edwards Lifesciences LLC. 
 
 
- pg 64 of 80 - 
13.0  APPENDIX 2: SAMPLE SUBJECT INFORMED CONSENT FORM AND HIPAA 
AUTHORIZATION 
 
Subject Informed Consent form for Participation in Research 
Introduction 
You are being asked to participate in a research study that will evaluate the Carpentier-
Edwards® PERIMOUNT® Magna® Mitral/Magna Mitral Ease™ Bioprostheses, model 
7000/7000TFX/7200TFX/7300/7300TFX (also referred to as Magna Mitral valve). The Magna 
Mitral valve, Model 7000/7000TFX and Model 7200TFX received FDA approval in August 2008 
and July 2009, respectively. Model 7300/7300TFX received FDA approval in June 2010. 
 
You are being asked to participate in this research study because your mitral valve is not 
working properly and your doctor determined that it needs to be replaced.  This Magna Mitral 
valve will be used to replace your diseased mitral valve or a previously implanted prosthesis.  
Your participation in this research study is voluntary. 
 
Background and Purpose 
The purpose of this research study is to learn about the safety and how well the Magna Mitral 
Valve works for up to eight years in a minimum of 250 subjects at up to 25 hospitals.  It is 
anticipated that the research study will be completed in approximately 10 years. 
 
Procedures 
You will undergo routine evaluation including: medical history evaluation, a physical exam, a 
transthoracic echocardiogram (a probe is placed on your chest and images of your heart are 
recorded) and laboratory blood work.  
 
The Study Doctor will screen you to decide if you are eligible to participate in this research 
study.  If you are eligible, the Study Doctor will explain the study procedures. 
 
A representative from Edwards Lifesciences may be present in the operating room at the time of 
your surgery. 
 
After your surgery you will be asked to remain in contact with your cardiologist and/or Study 
Doctor for a minimum of eight years to monitor your medical progress.  Regular visits after the 
surgery include tests such as laboratory blood work and transthoracic echocardiography.  This 
is the standard procedure for all  patients who have an artificial valve.  No other procedures will 
be required for this study.  
 
Risks  
The treatment of choice for your disease is heart valve replacement, and that alternative valves 
are available.  The risks of placement of the valve is similar to those associated with any heart 
valve replacement surgery.  As with any prosthetic heart valve, there is a possibility that 
unforeseeable adverse events could develop that were not anticipated.  Your Study Doctor has 
already discussed any appropriate alternative procedures and these adverse events in detail.   

Magna Mitral Post Approval Study Protocol 2006-05   
 
 REV I  November 18, 2013  
 
 
 
 
 
 This document and the information contained herein is considered Proprietary and Confidential  
and may not be reproduced, used or disclosed without written permission from Edwards Lifesciences LLC. 
 
 
- pg 65 of 80 - 
 
If you have a related complication after the surgery, as described to you by your Study Doctor, 
you should contact _____________________________(the doctor responsible for your follow-
up) at _____________________________. 
 
Benefits 
You may or may not receive any direct benefit from this research study of the Magna Mitral 
Valve, but others may benefit in the future from your participation.  Your participation in this 
study is voluntary and it is your right to refuse to participate or withdraw without penalty or loss 
of benefits to which you are otherwise entitled. 
 
Financial Obligation and Liability 
Edwards Lifesciences is the manufacturer of the Magna Mitral valves and the sponsor of this 
study.  Edwards Lifesciences will charge the hospital a fee for purchase of the prosthesis, and 
such charges will be incorporated in the hospital’s charges to you.  This charge is comparable to 
the cost of other commercially available prostheses.  You or your insurance company will be 
responsible for the cost of this procedure.  You will not be paid for your participation in this 
study.  Edwards Lifesciences shall not compensate you for injury or for any additional expenses 
incurred because of this study. 
 
The hospital cannot assume liability for injury directly attributable to the use of this particular 
valve or any other valve.  In the event physical injury occurs as a result of participating in this 
study, the necessary facilities, emergency treatment and professional medical services will be 
available to you, just as they are to the general community. 
 
Confidentiality and Anonymity 
After surgery, the doctor who implanted the valve or one of his staff members will give you a 
card called the Implant Data Card.  This card has the name and contact information of the 
surgeon who implanted the valve as well as the name of the hospital where you had the 
surgery.  This card has information that helps Edwards Lifesciences to indentify the valve that 
was implanted in your heart.  This card allows you to inform healthcare providers what type of 
implant you have when you seek care.   
 
Upon implantation of the valve, the data collected from your participation may be used for 
publications on the results of the heart valve you have received.  Your participation in this study 
will remain confidential and any data that may be published will not reveal your identity. 
Information that is derived from this study will be given to the Edwards Lifesciences and to 
Federal and other Regulatory agencies, as required in the interest of public safety and 
regulations.  The U.S. Food and Drug Administration, for example, may inspect research 
records and learn your identity if this study falls within its jurisdiction.  By participating in this 
study, you agree to allow representatives of Edwards Lifesciences, who are involved with this 
study to have access to your medical records concerning the device. You will also allow them to 
photocopy information from your medical records for study purposes. 
 

Magna Mitral Post Approval Study Protocol 2006-05   
 
 REV I  November 18, 2013  
 
 
 
 
 
 This document and the information contained herein is considered Proprietary and Confidential  
and may not be reproduced, used or disclosed without written permission from Edwards Lifesciences LLC. 
 
 
- pg 66 of 80 - 
As part of this study, Edwards Lifesciences seeks to gather data in order to assess the costs of 
the procedure and hospital services prior to, during and following the procedure, and that you 
are being asked to sign a separate Medical Billing Release Form.  Signing the Medical Billing 
Release Form will only affect whether cost information is collected and will have no impact on 
your consent to participate in all other aspects of the study. 
While participating in this study, you will not participate in any other research project without 
approval from the Study Doctor.  This is to protect you from possible injury arising from such 
events as extra blood draws, x-rays, interaction of research drugs, or similar hazards. 
 
Any significant new findings that develop during the research study which may relate to your 
willingness to continue your participation will be provided to you by the Study Doctor.  The study 
investigator may choose to terminate your participation, if you fail to follow the study guidelines, 
or in view of new information, at any time during the study.  
 
All forms of medical diagnosis and treatment, whether routine or experimental, involve some risk 
of injury.  In spite of all precautions, you might develop medical adverse events from 
participating in this study.  If such adverse events arise, the Study Doctor will assist you in 
obtaining appropriate medical treatment, but this study does not provide financial assistance for 
additional medical or other costs.  You may withdraw your consent to participate in this study 
and discontinue participation without penalty at any time.  You do not waive any liability rights 
for personal injury by signing this form. 
 
Voluntary Participation and Termination 
You are voluntarily agreeing to participate in this research study and accept the program as 
outlined above.  If the study design or the use of the information is to be changed, you will be 
informed and your consent will be re-obtained.  Please tell your doctor right away if you wish to 
stop participating in this study.  If you decide to stop being a part of the study, your doctor will 
tell you if there will be any effects or consequences.  For your safety, your doctor may ask you 
to continue to receive care, such as medical tests, even after you quit the study. 
 
You acknowledge that you have read, or have had read to you, the information provided above.  
You have been given an opportunity to ask questions and all of you questions have been 
answered to your satisfaction.  You also acknowledge that you have been given a copy of this 
Consent Form. 
 
 
BY SIGNING THIS FORM, I WILLINGLY AGREE TO PARTICIPATE IN THE RESEARCH IT 
DESCRIBES. 
 
 
 
 
 
 
 
 
 
 
 
 
Subject’s Name 
 
 
 
Signature of Subject  
 
 
Date 
   
 
 
 
 
 

Magna Mitral Post Approval Study Protocol 2006-05   
 
 REV I  November 18, 2013  
 
 
 
 
 
 This document and the information contained herein is considered Proprietary and Confidential  
and may not be reproduced, used or disclosed without written permission from Edwards Lifesciences LLC. 
 
 
- pg 67 of 80 - 
SIGNATURE OF INVESTIGATOR 
I have explained the research to the subject, and answered all of his/her questions.  I believe 
that he/she understands the information described in this document and freely consents to 
participate. 
 
 
 
 
 
 
 
 
 
 
 
 
Name of Investigator 
 
 
Investigator’s Signature 
Date 
      
 Hospital 
       
 
 
SIGNATURE OF WITNESS (optional) 
My signature as witnessed certified that the subject signed this consent form in my presence as 
his/her voluntary act and deed. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Name of Witness  
 
 
 
 
Signature of Witness 
 
Date 
 

Magna Mitral Post Approval Study Protocol 2006-05   
 
 REV I  November 18, 2013  
 
 
 
 
 
 This document and the information contained herein is considered Proprietary and Confidential  
and may not be reproduced, used or disclosed without written permission from Edwards Lifesciences LLC. 
 
 
- pg 68 of 80 - 
Authorization (consent) to permit the use and disclosure of identifiable medical 
information (protected health information) for research purposes in the United States.  
 
Study Title: Carpentier-Edwards® PERIMOUNT® Magna® Mitral Pericardial Bioprostheses Model 
7000/7000TFX and Carpentier-Edwards® PERIMOUNT® Magna Mitral Ease™ Pericardial 
Bioprostheses Model 7200TFX/7300/7300TFX. 
 
 
Principal Investigator: (Insert PI name here) 
 
 
Participant’s Name: ___________________________________________________ 
 
 
1.  What is the purpose of this form? 
 
The research study in which you are participating may help researchers learn more about the 
causes, or how to prevent and treat your condition.  Researchers would like to use your health 
information for research.  This information may include data that identifies you.  Please carefully 
review the information below.  If you agree that researchers can use your personal health 
information, you must sign and date this form to give them your permission. 
 
2.  What personal health information do the researchers want to use? 
 
The researchers want to copy and use the portions of your medical record that they will need for 
their research.  If you enter a research study, information that will be used and/or released may 
include (but not limited to) the following: 
• 
The history and diagnosis of your disease; 
• 
Specific information about the treatments you received, including previous treatment(s) 
you may have had; 
• 
Information about other medical conditions that may affect your treatment; 
• 
Medical data, including laboratory test results, measurements, CT scans, MRIs, x-rays, 
and pathology results; 
• 
Information on side effects (adverse events) you may experience, and how these were 
treated; 
• 
Long-term information about your general health status and the status of your condition; 
• 
Data that may be related to tissue and/or blood samples that may be collected from you; 
and 
• 
Numbers or codes that will identify you, such as your medical record number. 
 
3.  Why do the researchers want your personal health information? 
 
(Insert reason for use of personal health information here) 
 
 

Magna Mitral Post Approval Study Protocol 2006-05   
 
 REV I  November 18, 2013  
 
 
 
 
 
 This document and the information contained herein is considered Proprietary and Confidential  
and may not be reproduced, used or disclosed without written permission from Edwards Lifesciences LLC. 
 
 
- pg 69 of 80 - 
4.  Who will be able to use your personal health information? 
 
(Insert your institution and department) will have access to the data than includes protected 
health information. 
 
(Insert your institution and department) will use your health information for research.  As part of 
this research, the below listed groups may have access to your information: (insert all groups 
that will have access to or receive information) 
• 
The study’s sponsor or representative of the sponsor; 
• 
Public Health agencies and other government agencies as authorized or required by 
law; 
• 
Other people or organizations assisting the company(ies) sponsoring the research with 
the research efforts; 
• 
Central laboratories, central review centers, and central reviewers.  The central 
laboratories and review agencies may also give your health information to those groups 
listed in the bullets above; 
• 
The Office of Human Research Protection (OHRP) and/or Food and Drug Administration 
(FDA) 
 
 
5.  How will information about you be kept private? 
 
Only researchers will have access to your information.  We will not release personal health 
information about you to others except as authorized or required by law and institutional policy.  
However, once your information is given to other organizations that are not required to follow 
federal privacy laws, we cannot assure that the information will remain protected. 
 
6.  What happens if you do not sign this permission form? 
 
Taking part in a research study is completely voluntary and there is no penalty if you choose not 
to participate.  If you decide not to sign this permission form you will not be able to take part in 
the research study for which you are being considered.  The choice is completely up to you. 
 
7.  If you sign this form, will you automatically be entered into the research study? 
 
No, you cannot be entered into any research study without further discussion and a separate 
consent.  After discussion, you may decide to take part in the research study.  At that time, you 
will be asked to sign a specific research consent form. 
 
8.  What happens if you want to withdraw your permission? 
 
You can change your mind at any time and withdraw your permission to allow your personal 
health information to be used in the research.  If this happens, you must withdraw your 
permission in writing.  Beginning on the date you withdraw your permission, no new personal 

Magna Mitral Post Approval Study Protocol 2006-05   
 
 REV I  November 18, 2013  
 
 
 
 
 
 This document and the information contained herein is considered Proprietary and Confidential  
and may not be reproduced, used or disclosed without written permission from Edwards Lifesciences LLC. 
 
 
- pg 70 of 80 - 
health information will be used for research.  However, researchers may continue to use the 
health information that was provided before you withdrew your permission. 
 
If you sign this form and enter the research study, but later change your mind and withdraw your 
permission, you will be removed from the research study at that time. 
 
To withdraw your permission, please contact the principal investigator at the number listed 
below.  The study team will make sure your written request to withdraw your permission is 
processed correctly. 
 
(Insert contact information for the principal investigator or study coordinator) 
 
9.  How long will this permission last? 
 
If you agree by signing this form that researchers can use your personal health information, this 
permission has no expiration date.  However, as stated above, you can change your mind and 
withdraw your permission at any time. 
 
 
 
 
Signatures 
You agree that your personal health information may be used for the research purposes 
described in this form. 
 
____________________________________________________________                
 
 
 
 
 
 
 
 
 
 
 
    
Subject’s Name  
 
 
Signature of Subject  
 
 
Date 
 
 
 
Person Obtaining Permission  
 
 
               
 
 
 
 
 
 
 
 
 
 
 
 
 
    
Name of Investigator 
 
 
Investigator’s Signature 
 
 
Date 
      
 
 

Magna Mitral Post Approval Study Protocol 2006-05   
 
 REV I  November 18, 2013  
 
 
 
 
 
 This document and the information contained herein is considered Proprietary and Confidential  
and may not be reproduced, used or disclosed without written permission from Edwards Lifesciences LLC. 
 
 
- pg 71 of 80 - 
Medical Billing Release Form 
 
1. 
Study subject’s Name: ____________________________________ 
2. 
Date of Birth: __/__/____ (mm/dd/yyyy) 
3. 
Study subject’s Medical Record Number: _____________________ 
4. 
Social Security Number: ___-__-____ 
5. 
Is study subject Medicare eligible? 
 
 YES 
 NO 
 
If yes, Medicare Beneficiary Number  ________________ 
 
The research study you have agreed to participate in to evaluate the Carpentier-Edwards 
PERIMOUNT Magna Mitral / Magna Mitral Ease Bioprostheses model 7000/7000TFX/7200TFX 
/7300/7300TFX (the “Magna Mitral valve”) includes gathering data in order to assess the costs 
of the valve replacement procedure and hospital services related to that procedure.   
 
By signing this form, you authorize the Edwards Lifesciences, which is the manufacturer of the 
Magna Mitral Valve and sponsor of the research study (the “Sponsor”) and its representatives to 
access and use the information set forth in items 1 through 5 above to collect copies of your 
medical bills for any hospital services potentially related to the valve replacement procedure, 
whether those services occur prior to, during, or following the procedure. 
 
In doing so, you authorize the Patient Accounting Department at any hospital where you receive 
care potentially related to the valve replacement procedure to disclose these billing records to 
the Sponsor.  This process may take up to 5 years following your enrollment in the study. 
 
You understand that this information collected by the Sponsor will be kept strictly confidential 
and be used solely to assess the medical expenses that occur as a result of the valve 
replacement procedure.  The cost information may be added to the pool of cost data collected in 
the study and included in summary form in publication, but any such data will not reveal the 
information set forth in items 1 through 5 above.   
 
Additionally, you understand that you have the right to: (1) refuse to sign this authorization; (2) 
withdraw this authorization at any time by giving written notice to the address listed at the 
bottom of this form, with the knowledge that this action will not affect any information collected 
before the notice of withdrawal is received; and (3) receive a copy of this authorization. 
 
6. 
This billing information may be collected from _______________ (study enrollment date) 
to _____________ (5 years from date of enrollment). 
 
7. 
Signature: ____________________________________   Study Subject  
 
 
 
 
 
 
 
 
 
 Proxy __________ 
 
 
 
 
 
 
 
 
 
 
(relationship) 
 
To withdraw authorization, forward notice of withdrawal to: [add contact information] 

Magna Mitral Post Approval Study Protocol 2006-05   
 
 REV I  November 18, 2013  
 
 
 
 
 
 This document and the information contained herein is considered Proprietary and Confidential  
and may not be reproduced, used or disclosed without written permission from Edwards Lifesciences LLC. 
 
 
- pg 72 of 80 - 
14.0  APPENDIX 3: ECHO CORE LAB PROTOCOL 
 

Echo Protocol 
Study # 2006-05 
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EDWARDS ECHOCARDIOGRAPHY GUIDELINE: CLINICAL STUDIES 
CONDUCTED FOR MITRAL BIOPROSTHESES 
 
REVISION D:  NOVEMBER 18, 2013 
 
 
 
 
 
 
 
 
 
 
 
 
Edwards Lifesciences LLC 
One Edwards Way 
Irvine, CA USA 92614 
 
 
Proprietary Data: This document and the information contained herein may not be reproduced, 
used or disclosed without written permission from Edwards Lifesciences LLC 

Echo Protocol 
Study # 2006-05 
 
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Table of Contents 
1 
CONTACT INFORMATION ................................................................................................................ 3 
1.1 
EDWARDS EUROPE .............................................................................. ERROR! BOOKMARK NOT DEFINED. 
1.2 
EDWARDS UNITED STATES / CANADA ................................................................................................... 3 
1.3 
CORE LAB EUROPE ............................................................................................................................ 3 
1.4 
CORE LAB UNITED STATES / CANADA ................................................................................................... 3 
2 
CLINICAL SITE PROCEDURES ............................................................................................................ 3 
2.1 
DATA COLLECTION ............................................................................................................................ 3 
2.2 
PERFORMING THE ECHO EXAM............................................................................................................ 3 
2.3 
SUBMITTING MEDIA TO THE EUROPEAN CORE LAB.................................................................................. 4 
2.4 
SUBMITTING MEDIA TO THE US / CANADA CORE LAB ............................................................................. 4 
3 
SPONSOR PROCEDURES .................................................................................................................. 5 
3.1 
MATERIALS ..................................................................................................................................... 5 
3.2 
DATA AUDITS .................................................................................................................................. 5 
4 
CORE LAB PROCEDURES .................................................................................................................. 5 
4.1 
RECEIVING EXAM MEDIA ................................................................................................................... 5 
4.2 
ECHO TRACKING CASE REPORT FORM (CRF) ......................................................................................... 5 
4.3 
ASSESS THE EXAM ............................................................................................................................ 6 
4.4 
DATA COLLECTION / CALCULATION ...................................................................................................... 7 
4.4.1 
Two-dimensional echo variables ........................................................................................... 7 
4.4.2 
Left Ventricle Ejection Fraction .............................................................................................. 8 
4.4.3 
Doppler Mitral Valve ............................................................................................................. 8 
4.4.4 
Doppler LVOT ......................................................................................................................... 9 
4.4.5 
Doppler Aortic Valve .............................................................................................................. 9 
4.4.6 
Calculated Variables ............................................................................................................ 10 
4.4.7 
Left Ventricle Assessment .................................................................................................... 10 
4.4.8 
Mitral Valve Regurgitation .................................................................................................. 11 
4.4.9 
Mitral Valve Stenosis ........................................................................................................... 11 
4.4.10 
Non-study valve assessment................................................................................................ 11 
4.5 
RECORDS ...................................................................................................................................... 12 
 
Attachment 1: Core Lab Shipment Log  
Attachment 2: Core Lab Receipt Log 
Attachment 3: Echo Tracking Form 
Attachment 4: Case Report Form 
 

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Contact Information 
1.1 
Edwards United States / Canada/ Europe 
  
 
                                                  
 
1.2 
Core Lab Europe 
 
 
 
 
  
 
 
 
 
  
1.3 
Core Lab United States / Canada 
 
 
 
 
 
 
 
 
 
 
 
 
2 Clinical Site Procedures 
2.1 Data Collection 
The Clinical site should record the date of the exam, time period, reason for the exam, 
and a physical assessment of the patient on the Echocardiography Tracking Data Form.  
Physical assessments are to include heart rate, height, weight, and blood pressure. 
2.2 Performing the Echo Exam 
Echocardiography exams are to be performed for each time point as specified in the 
study’s Clinical Protocol.  The examinations should be conducted as on the example CD 
provided by the Core lab.  The following views should be obtained: 

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Study # 2006-05 
 
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- parasternal long axis view 
- parasternal short axis view  
- apical four chamber view 
- apical two chamber view 
- apical three chamber view (apical long axis) 
- subcostal four chamber 
- subcostal short axis, if necessary 
- right parasternal, if necessary 
- right suprasternal, if necessary 
 
The sonographer should record 3 beats per view for patients in sinus rhythm and at 
least 5 beats per view for patients in atrial fibrillation. 
2.3 Submitting Media to the European Core Lab 
Echo exams should be saved to CD, DVD, or Tape.  The preferred format is AVI.  
Information that can identify the study patient should not be included in the image, or 
media label.  The media should be labeled with the patient’s study identification 
number, initials, time interval and date of assessment.  Every echo submission needs to 
be accompanied by the Echo Tracking Form.  Finalized echo media should be sent 
together with the respective Echo Tracking Form to the respective Core lab listed in 
section 1. 
Alternatively, the echo media can be collected from the site by the respective monitor. 
 
The person (site or sponsor personnel) who sends the echo media to the Core lab 
should document this on the Core lab Shipment Log (see attachment 1). 
2.4 Submitting Media to the US / Canada Core Lab 
Echo exams should be saved to CD, DVD, or Tape.  The preferred format is DICOM 
format on CD, with a DICOMDIR (DICOM Directory) file.  Information that can identify 
the study patient should not be included in the image, or media label.  The media should 
be labeled with the patient’s study identification number, initials, time interval and date 
of assessment.  Every echo submission needs to be accompanied by a copy of the Echo 

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Tracking Form.  Finalized echo media should be sent together with the respective Echo 
Tracking Form to the respective Core lab listed in section 1. 
 
Alternatively, the echo media can be collected from the site by the respective monitor. 
 
The person (site or sponsor personnel) who sends the echo media to the Core lab 
should document this on the Core lab Shipment Log (see attachment 1). 
3 Sponsor Procedures 
3.1 Materials 
Upon request, sponsor will provide the study sites with CDs, DVDs or video 
tapes.   
3.2 Data Audits 
The sponsor may conduct an audit of the Core Lab(s) at least once a year. The 
purpose of the audit is to verify that the conditions of the consulting agreement 
are being met, ensure proper storage of study media, and ensure study data are 
complete and accurate   An audit of study data may be accomplished by a review 
of echo reports (print-outs from the echo machine or handwritten) or by 
observing the Core Lab complete a series of evaluations of study media.    
  
4 Core Lab Procedures 
4.1 
Receiving Exam Media 
The echo core lab should record all incoming echo media on the Core Lab 
Received log (See Attachment 2). Echos should be assessed within 4 weeks after 
receipt. The Core lab should inform the sponsor immediately if received 
echocardiographic images are not evaluable or of poor quality.  
4.2 
Echo Tracking Form 
 
   Verify the label on the media corresponds with the echo tracking form 

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4.3 
Assess the Exam 
The quality of the echo will be assessed using the following scale: 
Table 1: Echo Quality 
Rating 
Definition 
Excellent 
excellent visualization of all structures of the heart 
Good 
good visualization of LV, LA, LVOT, artificial valve and the 
endocardial borders 
Fair 
fair visualization of LV, artificial valve and LVOT; structures 
and borders can be detected 
Unreadable 
inadequate visualization of endocardial borders, artificial 
valve and LVOT; structures and borders cannot be detected 
 
 
The quality of the Doppler will be assessed using the following scale: 
Table 2: Doppler Quality 
Rating 
Definition 
Excellent 
Pulsed wave Doppler and continuous wave Doppler 
envelope are distinct and sharp, peak systolic, diastolic, in 
color mode atrial reversal velocities can be obtained in 
excellent pattern 
Good 
Pulsed wave Doppler and continuous wave Doppler 
envelope are distinct, peak systolic, diastolic, and atrial 
reversal velocities in color doppler with precise information 
Fair 
reduced quality of continuous and pulsed wave doppler 
curves, but doppler envelopes are readable, peak systolic, 
diastolic, and atrial reversal velocities can be obtained 
Unreadable 
fails to yield peak systolic, diastolic, and atrial reversal 
velocities, color doppler not readable 

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4.4 
Data Collection / Calculation 
4.4.1 Two-dimensional echo variables 
The variables listed in Table 3 will be measured. 
Table 3: 2D Echo Variables 
Variable 
Unit 
Plausible 
Range 
Measured by 
Interventricular Septal 
thickness (IVS) 
mm 
5 – 30 
End-diastolic endocardial border-to-
endocardial border of the interventricular 
septum, assessed in the parasternal long-
axis view below the level of the mitral 
leaflets, perpendicular to the visually 
assessed long-axis of the left ventricle; 
excluding RV trabeculae. 
Left Ventricular 
Internal Diameter  
in diastole (LVEDD) 
mm 
30 – 90 
End-diastolic endocardial border-to-
endocardial border of the LV cavity 
assessed in the parasternal long-axis view 
below the level of the mitral leaflets, 
perpendicular to the visually assessed long-
axis of the left ventricle. 
Posterior Wall 
thickness (end 
diastolic) (PW) 
mm 
5 – 30  
End-diastolic endocardial border-to-
epiocardial border of the LV posterior wall, 
assessed in the parasternal long-axis view 
below the level of the mitral leaflets, 
perpendicular to the visually assessed long-
axis of the left ventricle; excluding the 
pericardial space. 
Left Ventricular 
Internal Diameter  
in systole (LVESD) 
mm 
5 – 90  
Systolic endocardial border-to-endocardial 
border of the LV cavity assessed in the 
parasternal long-axis view below the level 
of the mitral leaflets, perpendicular to the 
visually assessed long-axis of the left 
ventricle, at the time of minimal LV 
diameter. 
Left Atrium (LA) 
mm 
19 – 70  
Systolic endocardial border-to-endocardial 
border of the LA cavity assessed in the 
parasternal long-axis view, perpendicular to 
the visually assessed long-axis of the left 
ventricle, at the time of maximal LA size and 
measured at the location of maximal LA 
diameter. 
Left Ventricular 
Outflow Tract (LVOT) 
mm 
14 – 30 
Mid-systolic endocardial border-to-
endocardial border of LVOT ~ 1 cm below 
level of aortic valve annulus that correlates 
with location of LVOT pulsed-wave Doppler 
sample volume, assessed in the parasternal 
long-axis view, perpendicular to the visually 
assessed long axis of the LVOT. 

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4.4.2 Left Ventricle Ejection Fraction 
Ejection Fraction can be measured visually or using Simpson’s method.  If Simpson’s 
method is used, the left ventricular end diastolic and end systolic volume are to be 
measured and recorded. 
Table 4: Ejection Fraction 
Variable 
Unit 
Plausible Range 
Left Ventricular 
Ejection Fraction 
(LVEF) 
% 
1 – 100  
4.4.3 Doppler Mitral Valve 
The variables listed in Table 5 will be measured. 
Table 5: Doppler Mitral Valve 
Variable 
Unit 
Plausible 
Range 
Measured / Calculated by 
Mitral Valve Peak 
Flow Velocity 
(VmaxMV) 
m/s 
0.5 – 3.0 
Continuous-wave Doppler envelope 
from apical window: maximal shift from 
baseline during antegrade flow through 
the mitral valve in diastole (E-wave or 
A-wave). 
Mean Pressure 
Gradient: Mitral 
Valve (MPG MV) 
mm Hg 
1.0 – 20.0  
Continuous-wave Doppler envelope 
from apical window: computer-assisted 
planimetry of area under the spectral 
Doppler envelope of antegrade flow 
through the mitral valve in diastole, 
from flow onset (E-wave) until end-
diastole as determined by ECG QRS 
onset. (Note: zero velocity during late 
diastole should be included in the 
planimetry to avoid over-estimation of 
mean transmitral gradient). 
Peak Pressure 
Gradient: Mitral 
Valve (PPG MV) 
mm Hg 
1.0 – 36.0  
Either: (4 x VmaxMV2 as determined 
above, or the computer-generated peak 
gradient derived from MV MPG 
continuous-wave Doppler planimetry 
above. 
Mitral Valve Time 
Velocity Integral 
(TVI MV) 
cm 
50 - 999 
From MV MPG planimetry as above, the 
area under the curve of the continuous 
wave spectral Doppler signal for 
antegrade transmitral flow during 
diastole from an apical window. 

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4.4.4 Doppler LVOT 
The variables listed in Table 6 will be measured.  
Table 6: Doppler LVOT 
Variable 
Unit 
Plausible 
Range 
Measured by 
LVOT Time 
Velocity Integral 
(TVI LVOT) 
cm 
50 – 300 
Pulsed-wave spectral Doppler of the 
LVOT from an apical window with the 
sample volume ~ 1 cm below the aortic 
valve annulus: area under the curve 
using computer-assisted planimetry of 
the Doppler envelope, from flow onset 
through flow cessation. 
Heart Rate (HR) 
min-1 
35 – 199  
Determined by QRS R-R interval () at the 
time of pulsed-wave Doppler 
assessment of the LVOT. HR may be 
derived from the echocardiographic 
ECG sensor if it is accurate, or is 
calculated as 6 x 104 / R-R interval (ms) 
4.4.5 Doppler Aortic Valve 
The variables listed in Table 7 will be measured. 
Table 7: Doppler Aortic Valve 
Variable 
Unit 
Plausible 
Range 
Measured / Calculated by 
Aortic Valve Peak 
Flow Velocity 
(VmaxAV) 
m/s 
0.5 – 4.0 
Continuous-wave spectral Doppler from 
apical, right parasternal or suprasternal 
window: maximal shift from baseline 
during antegrade flow through the 
aortic valve in systole. 
Mean Pressure 
Gradient: Aortic 
Valve (MPG AV) 
mm Hg 
1.0 – 39 
Continuous-wave spectral Doppler from 
apical, right parasternal or suprasternal 
window: computer-assisted planimetry 
of area under spectral Doppler 
envelope of antegrade flow through 
aortic valve in systole  
Aortic Valve Time 
Velocity Integral 
(TVI AV) 
cm 
50 – 999 
Continuous-wave spectral Doppler from 
apical, right parasternal or suprasternal 
window: area under the curve using 
computer-assisted planimetry of the 
Doppler envelope, from flow onset 
through flow cessation. 

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4.4.6 Calculated Variables 
The variables listed in Table 8 will be measured. 
Table 8: Calculated Variables 
Variable 
Unit 
Plausible 
Range 
Calculated by 
Stroke Volume 
(SV) 
mL 
30 – 200  
Derived as the product of TVI LVOT 
(cm)and cross-sectional area of the 
LVOT (= π x ((LVOT diameter/2)^2) 
(cm2) 
Cardiac Output 
(CO) 
L/min 
2.0 – 8.0  
Derived as the product of SV (cm3) and 
HR (min-1): SV x HR/1000 
Cardiac Index (CI) L/min/m2 1.0 – 4.0  
Derived as the ratio of CO (L/min) to 
body surface area. 
Effective Orifice 
Area: Mitral 
Valve (EOA MV) 
cm2 
1.0 – 8.0  
Derived using the continuity equation 
and the values to TVI MV, TVI LVOT and 
LVOT cross-sectional area (CSA, 
described above): 
EOA MV = (TVI LVOT x CSA LVOT) / TVI 
MV. 
4.4.7 Left Ventricle Assessment 
The left ventricle will be assessed for the presence of the conditions listed in Table 
9.  Other conditions may also be noted. 
Table 9: Left Ventricle Assessment 
Finding 
Definition 
Significant wall motion 
abnormality  
Defined as hypokinesis, akinesis or dyskinesis 
of ≥ 1 anterior circulation myocardial segment 
or ≥ 2 posterior circulation myocardial 
segments. 
Apical and/or Left Atrial 
Thrombus 
Defined as a soft-tissue density mass clinically 
consistent with thrombus noted in the left 
atrium or left ventricle. 
Pericardial Effusion 
Defined as an echo-lucent space external to 
and adjacent to the heart, clinically consistent 
with pericardial effusion. 
Trace/Minimal: Pericardial effusion evident 
only in systole but not in diastole. 
Small: Pericardial effusion larger than trace but 
no more than 1 cm in maximal diameter, 
Moderate: Pericardial effusion larger than 
small but no more than 2 cm in maximal 
diameter, 
Large: Pericardial effusion larger than 
moderate 

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4.4.8 Mitral Valve Regurgitation 
The Mitral valve will be assessed for the presence of the regurgitation.  If 
regurgitation is present the location of the leak will be noted as paravavlular, 
central, or indeterminate.  Regurgitation will also be graded as described in Table 
10.  The method of calculation for mitral regurgitation will be noted as Color 
Doppler, Regurgitant Fraction, PISA, or Pulmonary Vein Flow. 
 
Table 10: Mitral Valve Regurgitation 
Finding 
Definition 
+1 Trivial / Trace  
Physiological regurgitation, typically 
penetrating no more than 1 cm into the left 
atrium and/or a small non-holosystolic 
regurgitation jet. 
+2 Mild 
< 20% ratio of regurgitant jet area to left atrial 
area. 
+3 Moderate 
20 – 40% ratio of regurgitant jet area to left 
atrial area. 
+4 Severe 
> 40% ratio of regurgitant jet area to left atrial 
area. 
4.4.9 Mitral Valve Stenosis 
The Mitral valve will be assessed for the presence or absence of the stenosis.  
Stenosis is present if there is significant antegrade flow acceleration across the 
mitral valve in diastole, and/or a mean transmitral gradient > 6 mm Hg 
4.4.10 
Non-study valve assessment  
If the echo exam allows, the non study valves (aortic, tricuspid, or pulmonic) should 
be assessed for the presence of the regurgitation and stenosis.    Regurgitation will 
also be graded as described in Table 11.  
 
Table 11: Non-study Valve Regurgitation 
Finding 
Definition 
None / Trivial  
Clinical assessment of no regurgitation or 
physiological regurgitation. 
Mild 
Clinical assessment of mild regurgitation. 
Moderate 
Clinical assessment of moderate regurgitation. 
Severe 
Clinical assessment of severe regurgitation. 
 

Echo Protocol 
Study # 2006-05 
 
Revision D: November 2013                                                                 12 of 20                                                               
Confidential 
 
Stenosis will also be graded as described in Table 12.   
Table 12: Non-study Valve Stenosis 
Finding 
Definition 
None / Trivial  
Clinical assessment of no stenosis or 
hemodynamically insignificant. 
Mild 
Clinical assessment of mild stenosis. 
Moderate 
Clinical assessment of moderate stenosis. 
Severe 
Clinical assessment of severe stenosis. 
4.5 
Records 
Echo media and copies of echo reports and Case Report Forms will be filed in a secure 
location for the duration of the study.  Only authorized Core Lab personnel should have 
access to the media and data.  Original (white) and yellow Case Report Forms (CRF) will be 
sent to or collected by the sponsor.  The pink copy of the Echocardiography Data CRF 
remains at the Clinical site.  Alternative to 3-part NCR Echocardiography Data CRF is 
permissible with Sponsor prior approval. Originals or copies of the Echocardiography 
Tracking Data Form will be provided to the Core Lab. 
 

Echo Protocol 
Study # 2006-05 
 
Revision D: November 2013                                                                 13 of 20                                                               
Confidential 
 
 
 
 
 
 
ATTACHMENT 1 
CORELAB SHIPMENT LOG 

Echo Protocol 
Study # 2006-05 
 
Revision C: June 2010                                                                 15 of 20                                                               Confidential 
 
 
 
 
 
ATTACHMENT 2 
CORELAB RECEIVED LOG 

Echo Protocol 
Study # 2006-05 
Study Number 2006-05 
Carpentier-Edwards PERIMOUNT Magna Mitral Valve 
Echocardiography Tracking 
Data FORM 9 
 
 
 
Patient Study ID #  2 
0 
0 
6 
0 
5 
 
 
 
 
Patient Initials (First, Last)  
 
 
Clinic #   
 
 
 
Revision C: June 2010                                                                 17 of 20                                                               Confidential 
 
 
 
 
 
ATTACHMENT 3 
ECHO TRACKING FORM 
 

Echo Protocol 
Study # 2006-05 
Study Number 2006-05 
Carpentier-Edwards PERIMOUNT Magna Mitral Valve 
Echocardiography Tracking 
Data FORM 9 
 
 
 
Patient Study ID #  2 
0 
0 
6 
0 
5 
 
 
 
 
Patient Initials (First, Last)  
 
 
Clinic #   
 
 
 
Revision C: June 2010                                                                 18 of 20                                                               Confidential 
 
 
Please Provide The Following Information: 
1. 
ECHO DATE:  __ __ __ / __ __ / __ __ __ __ 
 
 
 
 
MMM DD 
YYYY 
2. 
TIME PERIOD: (Required preoperatively, at discharge, 6-months, 1, 2, 4, 6 and 8 year follow-up visits) 
    
   Preoperatively (≤ 6 months prior to implant) 
 
 Discharge or 30 days 
 
 6 Months (3-6 months) 
 
 1 Year  (11 – 13 months)  
 
 2 Years  (23 – 25 months) 
 
 4 Years  (47 – 49 months) 
 
 6 Years  (71 – 73 months) 
 
 8 Years  (95 – 97 months) 
 
 Other (Specify):   
 
 Months 
 Years 
 
3. 
ECHO RECORDED ON (MEDIA): 
 
 
 Tape    
 CD 
 
 
 MOD    
 DVD 
4. 
REASON FOR ECHO: 
 
 Per protocol 
 
 Symptomatic, study valve related 
 
 Symptomatic, non-study valve related 
 
 Other  (Specify):  
 
 
 
 
 
5. 
PHYSICAL ASSESSMENT: 
 Heart Rate __ __ __ (BPM)  
 Height __ __ __  (cm) 
 
 Weight __ __ __ (kg)  
 
 Blood Pressure __ __ __ / __ __  __ (mmHg) 
 
 
6. 
DATE MEDIA SENT: 
 __ __ __ / __ __ / __ __ __ __ 
 
(OR COLLECTED) 
      MMM 
DD          YYYY 
 
 
 
 
 
 
 

Echo Protocol 
Study # 2006-05 
 
Revision C: June 2010                                                                 19 of 20                                                               Confidential 
 
 
 
 
ATTACHMENT 4 
CASE REPORT FORMS 
 

Echo Protocol 
Study # 2006-05 
Study Number 2006-05 
Carpentier-Edwards PERIMOUNT Magna Mitral Valve 
Core Lab Echocardiography 
Data  
FORM 10 
Page 20 of 20 
 
Patient Study ID #  2 
0 
0 
6 
0 
5 
 
 
 
 
Patient Initials (First, Last)  
 
 
Clinic #   
 
 
 
I have reviewed and approved all information on this form.  (Reviewing 
Physician’s Signature) 
Date 
/
/
MMM 
DD 
YYYY 
 
White and Yellow:  Return to Edwards Lifesciences, Clinical Affairs    Pink:  Retain for your Records 
PROPRIETARY DATA:  This document and information contained herein may not be reproduced, used, or disclosed without written permission of Edwards Lifesciences,  
 
Heart Valve Therapy Group, Clinical Affairs         Core Lab Echo Data, REV E 20100624 
Rev C: June 2010                                                              20 of 20 
1. 
Echo Date: 
__ __ __/__ __/__ __ __ __ 
 
 
 
 
MMM    DD 
YYYY 
2. 
Time Period: 
 
 Preoperatively 
 1 Year 
 6 Year 
 
 Discharge 
 2 Year 
 8 Year 
 
 6 Month 
 4 Year 
 Other (Specify):   
 
 
 Months 
 Years 
3. 
Transducer Position: 
 
 Transthoracic  
 
 Transesophageal 
 Other  (Specify):  
__________________ 
4. 
Echo Quality: (Select one) 
 
 Excellent 
 
 
 Good 
 
 Fair 
            
 Poor 
 
 Unreadable 
5. 
Doppler Quality: (Select 
one) 
 
 Excellent 
 
 
 Good 
 
 Fair 
 
 Unreadable 
6. 
2D Echo Variables: 
 
__ __  (mm) IVS 
 
__ __  (mm) LVEDD 
 
__ __  (mm) PW 
 
__ __  (mm) LVESD 
 
__ __  (mm) LA 
 
__ __  (mm) LVOT 
7. 
Left Ventricle Ejection Fraction: 
 
__ __ . __ (%) 
 Visual 
 
 
 Simpson’s 
 
__ __ __    (mL) LV EDV 
 
__ __ __    (mL) LV ESV 
8. 
Doppler Mitral Valve: 
 
__ . __ (m/s) 
Vmax MV 
 
__ __ . __  
(mmHg) MPG MV 
 
__ __ . __  
(mmHg) PPG MV 
 
__ __ . __  
(cm) 
 
TVI MV 
9. 
Doppler LVOT: 
 
__ __ . __  
(cm) 
 TVI LVOT 
 
__ __ __  
(min-1) HR (LVOT PW Doppler) 
10. Doppler Aortic Valve: 
 
__ . __ (m/s) 
Vmax AV 
 
__ __ . __  
(mmHg) 
MPG AV 
 
__ __ . __  
(cm) 
 
TVI AV 
11. Calculated Variables: 
 
__ __ . __  
(mL)  
 
SV 
 
__ __ . __  
(L/min) 
 
CO 
 
__ . __  (L/min/m2) CI 
 
__ . __ __  
(cm2)  
EOA MV 
12. Left Ventricle Assessment (Check all that apply) 
 
 
No abnormalities 
 
 
Significant Wall Motion Abnormality 
 
 
Apical and/or Left Atrial Thrombi 
 
 
Pericardial Effusion 
 
 
 Trace / Minimal 
 
 
 Small 
 
 
 Moderate 
 
 
 Large 
 
 
 Other (Specify) _________________ 
14. 
Mitral Valve Stenosis:  
 No 
 Yes 
 Not evaluable 
 
13. 
Mitral Valve Regurgitation: 
 None 
 Not evaluable 
 
 
Site  
Severity 
Method of Calculation 
Paravalvular 
Leak 
 
+1 Trivial/Trace 
 
+2 Mild 
 
+3 Moderate 
 
+4 Severe 
 
Color Doppler 
 
Regurgitant Fraction 
 
PISA 
 
Pulmonary Vein Flow 
Central Leak 
 
+1 Trivial/Trace 
 
+2 Mild 
 
+3 Moderate 
 
+4 Severe 
 
Color Doppler 
 
Regurgitant Fraction 
 
PISA 
 
Pulmonary Vein Flow 
Indeterminate 
 
+1 Trivial/Trace 
 
+2 Mild 
 
+3 Moderate 
 
+4 Severe 
 
Color Doppler 
 
Regurgitant Fraction 
 
PISA 
 
Pulmonary Vein Flow 
15. 
Non-Study Valve Assessment (If available): 
Valve 
Stenosis 
Regurgitation 
Aortic  
 
None / Trivial 
 
Mild 
 
Moderate 
 
Severe 
 
Not Evaluable 
 
None / Trivial 
 
Mild 
 
Moderate 
 
Severe 
 
Not Evaluable 
Tricuspid 
 
None / Trivial 
 
Mild 
 
Moderate 
 
Severe 
 
Not Evaluable 
 
None / Trivial 
 
Mild 
 
Moderate 
 
Severe 
 
Not Evaluable 
Pulmonic 
 
None / Trivial 
 
Mild 
 
Moderate 
 
Severe 
 
Not Evaluable 
 
None / Trivial 
 
Mild 
 
Moderate 
 
Severe 
 
Not Evaluable 
 
16.  
COMMENTS:_________________________________________________________________________________________ 
 

Magna Mitral Post Approval Study Protocol 2006-05   
 
 REV I  November 18, 2013  
 
 
 
 
 
 This document and the information contained herein is considered Proprietary and Confidential  
and may not be reproduced, used or disclosed without written permission from Edwards Lifesciences LLC. 
 
 
- pg 73 of 80 - 
15.0  APPENDIX 4: INSTRUCTIONS FOR USE  
 
 
US 
Model 7000/7000TFX, Model 7200TFX and Model 7300/7300TFX 
 
Australia 
Model 7000TFX  
 
OUS (Outside US and excluding Australia) 
Model 7000TFX 
 
 

2. Indications for Use
The Carpentier-Edwards PERIMOUNT MAGNA mitral pericardial bioprosthesis
model 7000TFX 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
DO NOT RESTERILIZE THE BIOPROSTHESIS BY ANY METHOD. Exposure of
the bioprosthesis or container 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. 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 monitor the temperature that the device is
exposed to during transit and storage. If the indicator displays any
reading other than “OK” do not use the bioprosthesis. Please refer to
Packaging section (10.2) for further instructions.
DO NOT USE the bioprosthesis if the tamper evident seal on the jar is
broken.
DO NOT USE the bioprosthesis if expiration date has elapsed.
DO NOT USE the bioprosthesis if the container is leaking, damaged, or
the glutaraldehyde solution does not completely cover the
bioprosthesis.
DONOTEXPOSEthebioprosthesistoanysolutions,chemicals,antibiotics,
etc.,exceptforthestoragesolutionorsterilephysiologicalsaline
solution.Irreparabledamagetotheleaflettissue,whichmaynotbe
apparentundervisualinspection,mayresult.
DO NOT ALLOW the bioprosthesis to dry. It must be kept moist at all
times. Maintain tissue moisture with sterile physiological saline
irrigation on both sides of the leaflet tissue.
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.
DO NOT USE the bioprosthesis if it has been dropped, damaged, or
mishandled in any way. Should a bioprosthesis be damaged during
insertion, do not attempt repair.
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.
DONOTOVERSIZE.Oversizingmaycausebioprosthesisdamageor
localizedmechanicalstresses,whichmayinturninjuretheheartor
resultinleaflettissuefailure,stentdistortionandvalveregurgitation.
Clinical data that establish the safety and efficacy of the bioprosthesis for use in
patients under the age of 20 are not available; therefore, we recommend careful
consideration of its use in younger patients.
The decision to use a bioprosthesis must ultimately be made by the surgeon on
an individual basis after a careful evaluation of the short- and long-term risks
and benefits to the patient and consideration of alternative methods of
treatment.
Long-term durability has not been established for bioprostheses. Serious
adverse events, sometimes leading to replacement of the bioprosthesis and/or
death, may be associated with the use of prosthetic valves (see 6. Adverse
Events). A full explanation of the benefits and risks should be given to each
prospective patient before surgery.
Note:Bioprosthesesshouldbeusedwithcautioninthepresenceofsevere
systemichypertensionorwhentheanticipatedpatientlongevityislongerthanthe
knownlongevityoftheprosthesis(see7.ClinicalStudies).
Careful and continuous 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.
Recipients of prosthetic heart valves who are undergoing dental procedures
should receive prophylactic antibiotic therapy to minimize the possibility of
prosthetic infection. Bioprosthetic heart valve recipients should be maintained
on anticoagulant therapy (except where contraindicated) during the initial
healing stages after implantation, approximately 2 to 3 months. Anticoagulants
should then be discontinued over a period of 10 days, except in those patients
for whom indefinite anticoagulant protection is indicated, i.e., in the absence of
sinus rhythm and in patients with a dilated left atrium, calcification of the atrial
wall, or history of previous atrial thrombus. However, the appropriate
anticoagulation therapy must be determined by the physician on an individual
basis (Ref. 7).
Adequate rinsing with physiological saline is mandatory before implantation to
reduce the glutaraldehyde concentration (see 11.4 Handling and
Preparation Instructions). No other solutions, drugs, chemicals, antibiotics,
etc., should ever be added to the glutaraldehyde or rinse solutions, as
irreparable damage to the leaflet tissue, which may not be apparent under
visual inspection, may result.
5. Precautions
•
Do not sterilize the sizers model 1177HP and handles model 1111 or 1117 in
their shipping containers.
•
Use only the sterilization tray model TRAY1177HP to sterilize the sizers and
the handles.
•
The outside of the jar is not sterile and must not be placed in the sterile
field.
•
To avoid contamination, it is strongly recommended that the jar of a
Carpentier-Edwards PERIMOUNT MAGNA mitral pericardial bioprosthesis
model 7000TFX not be opened unless implantation is certain.
•
Adequate rinsing with physiological saline must be performed before
implantation to reduce the glutaraldehyde concentration.
•
Avoid contact of the leaflet tissue or the rinse solution with towels, linens,
or other sources of lint and particulate matter that may be transferred to the
leaflet tissue.
2

•
Do not allow the leaftlet tissue to contact the bottom or sides of the rinse
basin.
•
Glutaraldehyde may cause irritation of the skin, eyes, nose, and throat.
Avoid prolonged or repeated exposure or breathing of the solution. Use only
with adequate ventilation. If skin contact occurs, immediately flush the
affected area with water; in the event of contact with the eyes, seek
immediate medical attention. For more information about glutaraldehyde
exposure, please refer to the Material Safety Data Sheet available from
Edwards Lifesciences.
•
Always deploy the Tricentrix holder system fully to minimize the risk of
suture entrapment. It will snap into a secured and locked position.
•
A serial number tag is attached to the sewing ring of each bioprosthesis by a
suture. This serial number should be checked against the number on the jar
and implantation data card; if any difference is noted, the bioprosthesis
should be returned unused. Care must be taken to ensure that the serial
number tag does not come in contact with the leaflet tissue during rinsing.
Inspection of the bioprosthesis and removal of the serial number tag should
be performed just prior to implantation. Care should be exercised to avoid
cutting or tearing the sewing ring cloth during removal of the serial number
tag.
•
Careful handling is required for all implantable devices. If the bioprosthesis
is dropped, damaged, or mishandled in any way, it must not be used for
human implantation.
•
Toavoiddamagetothedelicatebioprostheticleaflettissue,asaresultof
contactwithcalciumdeposits,adequateremovalofcalciumdepositsfromthe
patient’sannulusmustbeperformedbeforeimplantation.
•
Handle the bioprosthesis only with Edwards Lifesciences accessories. Only
Edwards Lifesciences sizers 1177HP should be used during the selection of
the Magna mitral bioprosthesis size; other sizers may result in improper
bioprosthesis selection. Edwards Lifesciences sizers are marked for both size
and EOA to provide clinically relevant information during surgery and help
avoid oversizing (see 11.2 Accessories).
•
Oversizingmustbeespeciallyavoidedasitmaycausebioprosthesisdamage
orlocalizedmechanicalstresses,whichmayinturninjuretheheartorresult
inleaflettissuefailure,stentdistortionandregurgitation.
•
Special care must be exercised when using chordal preservation techniques
to avoid chordae entrapment by a strut.
•
Due to the relative flexibility of the frame, care must be exercised to prevent
folding or deformation of the stent.
•
The surgeon should be familiar with the recommendations for proper sizing
and placement of the bioprosthesis according to the suture technique used
(see 11.5 Device Implantation).
•
The sewing ring is designed for a specific orientation: the scalloped part of
the sewing ring, between the two protrusions, should be placed across the
intercommissural anterior portion of the annulus and straddle the left
ventricular outflow tract.
•
Special care must be exercised to avoid placing a strut in front of the left
ventricular outflow tract, as this may impair the long-term hemodynamic
performance.
•
As with all prostheses that have open cages, free struts, or commissure
supports, care must be exercised to avoid looping or catching a suture
around a commissure, which would interfere with proper valvular function.
To avoid suture looping, it is essential to leave the deployed holder in place
until all knots are tied.
•
If the deployed holder attachment threads are cut, before at least all the
sutures adjacent to the struts are tied down, the holder can no longer
prevent suture looping.
•
When using interrupted sutures, it is important to cut the sutures close to
the knots and to ensure that exposed suture tails will not come into contact
with the leaflet tissue.
6. Adverse Events
6.1 Observed Adverse Events
TheCarpentier-EdwardsPERIMOUNTMAGNAmitralpericardialbioprosthesis
model7000TFXusesthesamewireformframeandleafletattachmentasEdwards
Lifesciencespericardialmitralbioprosthesesmodels6900,6900Pand6900PTFX.
Three(3)multi-center,non-randomized,prospectivenon-USclinicalstudieswere
conductedwiththemitralpericardialbioprosthesismodel6900.Threehundred
one(301)patientshadisolatedmitralvalvereplacement(MVR)and62patients
haddoublevalvereplacement(DVR),wheretheaorticvalvewasreplacedwitha
Carpentier-EdwardsPERIMOUNTpericardialbioprosthesisaorticmodel.Inthefirst
study,bioprostheseswereimplantedbetween1984and1986;inthesecond
study,bioprostheseswereimplantedbetween1989and1994;andinthethird
study,bioprostheseswereimplantedbetween1996and1997.Patientswere
evaluatedpreoperatively,intraoperatively/atdischarge,at1year,andannually
thereafter.Adverseeventswerecapturedthroughoutthepostoperativeperiod.
Table1presentstheobservedratesforearlyevents(≤30daysforvalve-related
adverseevents),thelinearizedratesforlateevents(>30dayspostoperatively),
andtheactuarialadverseeventratesat1,5,and8yearspostoperatively.The
adverseeventrateswerebasedon363patientsatninecenters.Thecumulative
follow-upwas1100patient-yearswithameanfollow-upof3.0years(SD=
2.4years,range=0to8.2years).Preoperativeandoperativepatient
demographicsarepresentedinTables2and3.Effectivenessresultsarepresented
inTables4and5.
6.2 Potential Adverse Events
Adverse events potentially associated with the use of bioprosthetic heart valves
include:
•
Angina
•
Cardiac arrhythmias
•
Endocarditis
•
Heart failure
•
Hemolysis
•
Hemolytic anemia
•
Hemorrhage
•
Myocardial infarction
•
Prosthesis leaflet entrapment
•
Prosthesis nonstructural dysfunction
•
Prosthesis pannus
•
Prosthesis perivalvular leak
•
Prosthesis regurgitation
3

•
Prosthesis structural deterioration
•
Prosthesis thrombosis
•
Stroke
•
Thromboembolism
It is possible that these complications could lead to:
•
Reoperation
•
Explantation
•
Permanent disability
•
Death
OtheradverseeventsassociatedwiththeuseofCarpentier-EdwardsPERIMOUNT
mitralpericardialbioprosthesesmodel6900compiledfromtheliteratureand
fromreportsreceivedthroughtheEdwardsLifesciencescomplainthandling
systeminclude:stenosis,regurgitationthroughanincompetentvalve,
ventricularperforationbystentposts,malfunctionsofthevalveduetodistortion
atimplant,andfractureoftheElgiloywireformframe.
7. Clinical Studies
The safety endpoints captured in the prospective studies were complications;
blood analyses were used to confirm the absence or presence of certain
complications. The safety results are provided in Table 1. Effectiveness
endpoints were New York Heart Association (NYHA) functional classification and
echocardiographic assessments. Preoperative and operative patient
demographics are presented, followed by the effectiveness results. There are no
clinical data presently available demonstrating increased resistance of the
Carpentier-Edwards PERIMOUNT MAGNA mitral pericardial bioprosthesis model
7000TFX to calcification as compared to other commercially available
bioprostheses.
8. Individualization of Treatment
Bioprostheticheartvalverecipientsshouldbemaintainedonanticoagulant
therapy,exceptwherecontraindicated,duringtheinitialstagesafter
implantation,asdeterminedbythephysicianonanindividualbasis.Long-term
anticoagulantand/orantiplatelettherapyshouldbeconsideredforpatientswith
adilatedleftatrium,ahistoryofthromboticevents,anabsenceofsinusrhythm,
calcificationoftheatrialwall,orwithatrialfibrillationorflutter.Thedecisionto
useabioprosthesismustultimatelybemadebythephysicianonanindividual
basisafteracarefulevaluationoftheshort-termandlong-termrisksandbenefits
tothepatientandconsiderationofalternativemethodsoftreatment(Ref.7).
8.1 Specific Patient Populations
The safety and effectiveness of the Carpentier-Edwards PERIMOUNT MAGNA
mitral pericardial bioprosthesis model 7000TFX 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, or young adults.
9. Patient Counseling Information
Carefulandcontinuedmedicalfollowup(atleastbyanannualvisittothe
physician)isadvisedsothatvalve-relatedcomplications,particularlythose
relatedtomaterialfailure,canbediagnosedandproperlymanaged.Patients
withbioprosthesesareatriskfrombacteremia(e.g.,undergoingdental
procedures)andshouldbeadvisedaboutprophylacticantibiotictherapy.
PatientsshouldbeencouragedtocarrytheirImplantationDataCardatalltimes
andtoinformtheirhealthcareprovidersthattheyhaveamitralbioprosthetic
implantwhenseekingcare.
10. How Supplied
10.1 Available Models and Sizes
The Carpentier-Edwards PERIMOUNT MAGNA mitral pericardial bioprosthesis
model 7000TFX is available in labeled sizes 25, 27, 29, 31 and 33 mm (see Figure
1 for nominal specifications).
10.2 Packaging
The Magna mitral bioprosthesis is provided sterile and nonpyrogenic packaged
in glutaraldehyde, in a plastic jar to which a seal has been applied. 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
monitor the temperature that the device is exposed to during transit and
storage. Upon receipt of the bioprosthesis immediately inspect to see if the
indicator displays any reading other than “OK”, if so do not use the
bioprosthesis. Contact the local supplier or Edwards Lifesciences representative
to make arrangements for return, authorization and replacement. Any
bioprosthesis returned to Edwards Lifesciences must be shipped in its original
packaging in which it was received.
Warning: The bioprosthesis must be carefully inspected before
implantation for evidence of extreme temperature exposure or other
damage.
Due to the biological nature of this bioprosthesis and its sensitivity to physical
handling and environmental conditions, it cannot be returned, except as noted
above.
Note: Products found to have been subjected to freezing or excessive heat later
than 3 days following receipt will be considered to have resulted from
environmental conditions within the control of the customer, and subject to
replacement at customer’s expense.
10.3 Storage
The Magna mitral bioprosthesis should be stored at 10 °C to 25 °C
(50-77 °F). Stock inspection and rotation at regular intervals are recommended
to ensure that the bioprostheses are used before the expiration date stamped on
the package label.
Warning: Do not freeze. Always store bioprostheses in a dry,
contamination-free area. Any bioprosthesis that has been frozen, or is
suspected of having been frozen, should not be used for human
implantation.
4

11. Directions for Use
11.1 Physician Training
No special training is required to implant the Carpentier-Edwards
PERIMOUNT MAGNA mitral bioprosthesis model 7000TFX. The techniques for
implanting this bioprosthesis are similar to those for implanting any stented
mitral bioprostheses.
11.2 Accessories
Accessories available for use with the Magna mitral bioprosthesis are:
•
Tricentrix holder system
•
Carpentier-Edwards PERIMOUNT MAGNA mitral sizers 1177HP
•
Sterilization tray TRAY1177HP
•
Handles 1111 (universal), 1117 (mitral) or 1126 (single use)
All accessories are supplied non-sterile, except for the Tricentrix holder system
that is supplied sterile attached to the sterile bioprosthesis and the handle 1126
that is supplied sterile and is for single use only.
Sizers and Tray
Only sizers 1177HP must be used with the Magna mitral bioprosthesis.
Caution: Do not use other manufacturer’s valve sizers, or sizers for other
Edwards Lifesciences valve prostheses to size the Magna mitral bioprosthesis.
Use only the sizers 1177HP with attached handle (1111, 1117 reusable handles
or 1126 single use handle) to determine the appropriate Magna mitral
bioprosthesis size. Sizers 1177HP permit direct observation of their fit within the
annulus and are provided for each available Magna mitral bioprosthesis size.
The barrel of the sizers indicates the external stent diameter at the tip (Figure
1). The lip of the sizers replicates the sewing ring of the bioprosthesis, with its
scalloped anterior portion and black markings, to better determine the
outcomes of specific suture or subvalvular apparatus preservation techniques.
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 saddle the left ventricular outflow tract area.
Thesizers1177HPandtrayTRAY1177HParelabeledwithboththebioprosthesis
sizeandthemeanEffectiveOrificeArea(EOA).TheEOAincm2istakenfromthe1
to2yearpost-implantintervalasreportedinTable5.Thelabeledsizeisnota
standardizedmeasurementandmayvaryfromonemanufacturertoanother(or
betweendifferentmodelsofasamemanufacturer).Surgeonshaveaccesstoboth
thelabeledsizeandtheEOAatthetimeofsurgery,whichmayprovideclinically
relevantinformationontheexpectedhemodynamicperformance.Thismayhelp
determinetherightsizeforaparticularpatient,andpreventimpropersizing.
Placing sutures around the native annulus may reduce the size of the
bioprosthesis that can be implanted. It is recommended to size or re-size after
the sutures have been placed to avoid oversizing. Some techniques such as
everting mattress sutures or mitral subvalvular apparatus preservation may
further reduce the size of the bioprosthesis that can be implanted. When using
these techniques, it is recommended to pass the entire sizer, including the lip,
through the native annulus, to ensure enough clearance for the sewing ring or
the reefed preserved apparatus (Figure 10). The consistent performance of the
PERIMOUNT mitral bioprostheses makes oversizing unnecessary to achieve the
desired hemodynamic performance in most patients (Table 5).
Warning: 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 regurgitation.
Tricentrix Holder System and Handles
The holder/handle assembly consists of two (2) components: the Tricentrix
holder system that is mounted to the bioprosthesis, and a handle (1111, 1117 or
1126) that is attached to the Tricentrix holder system at the time of surgery
(Figure 2).
•
The handle 1111 is a universal stainless steel handle that can be used with
other Edwards Lifesciences prostheses (Figure 11).
•
The handle 1117 has been designed specifically for the mitral position: it is
longer to provide an easier access to the mitral valve in the case of a difficult
exposure, a deep thoracic cage or a minimally invasive access. Its nitinol
shaft is more flexible than stainless steel. With each sterilization cycle, it
returns to its original straight shape, for an easier attachment to the sizer or
holder (Figure 11).
Both handles 1111 and 1117 can be resterilized.
•
The handle 1126 has a long and thin stainless steel shaft and is intended for
single use only (Figure 11).
The Tricentrix holder has short legs and beveled edges to increase suturing
space and ease knot tying (Figure 12).
11.3 Accessory Sterilization
The 1126 handle is provided sterile and is intended for single use only. The
handles 1111 and 1117 and the sizers 1177HP are supplied non-sterile and must
be sterilized before using. The handles 1111 and 1117 and the sizers 1177HP
must be disassembled, cleaned, and re-sterilized prior to each use. Sizers and
handles should be examined for signs of wear, such as dullness, cracking, or
crazing, and should be replaced if any deterioration is observed. Caution: Do
not sterilize the sizers and handles 1111 or 1117 in their shipping containers.
Use only the sterilization tray TRAY1177HP to sterilize the sizers and the
handles.
The accessories can be sterilized using the following recommended autoclave
sterilization methods:
I. Gravity Displacement:
a) Wrapped:
Temperature:
270-279 °F (132-137 °C)
Exposure Time:
10-18 minutes
b) Unwrapped (“flash”):
Temperature:
270-279 °F (132-137 °C)
Exposure Time:
3 minutes
II. Prevacuum:
a) Wrapped:
Temperature:
270-279 °F (132-137 °C)
Exposure Time:
3-18 minutes
b) Unwrapped (“flash”):
Temperature:
270-279 °F (132-137 °C)
Exposure Time:
3 minutes
Each institution should use procedures that include biological indicators to
determine the effectiveness of the sterilization procedure.
5

11.4 Handling and Preparation Instructions
The bioprosthesis is packaged sterile in a plastic jar with a screw-cap closure and
seal. Before opening, carefully examine the jar for evidence of damage (e.g., a
cracked jar or lid), leakage, or broken or missing seals. Remove the seal and turn
the lid counter-clockwise to open the container. The bioprosthesis and Tricentrix
holder system within the container are sterile.
Caution: The outside of the jar is not sterile and must not be placed in
the sterile field. The contents of the jar should be handled in an aseptic
manner to prevent contamination.
Caution: Bioprostheses from containers found to be damaged, leaking,
without adequate glutaraldehyde, or missing intact seals must not be
used for human implantation.
Caution: It is strongly recommended that the jar of a Magna mitral
bioprosthesis not be opened unless implantation is certain. This is
necessary to reduce the risk of contamination, because it has been
established that glutaraldehyde alone is not a 100% effective sterilant
against all possible contaminants.
Warning: No attempt should be made to resterilize a Magna mitral
bioprosthesis.
Warning: Do not use the bioprosthesis if it has been dropped, damaged, or
mishandled in any way. Should a bioprosthesis be damaged during insertion, do
not attempt repair.
Warning: Do not grasp the leaflet tissue portion 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 bioprosthesis function.
Verify that the handle, 1111 or 1117, has been sterilized according to the
instructions provided in Section 11.3. If sterile, using handle 1111, 1117 or 1126,
attach the handle to the Tricentrix holder system and turn it clockwise until a
positive resistance is felt then remove the whole assembly (i.e., plastic sleeve,
clip, the Tricentrix holder system and bioprosthesis) from the jar.
A tag with a serial number is attached to the sewing ring of each bioprosthesis
by a suture. This serial number should be checked against the number on the jar
and implantation card; if any differences are noted, the bioprosthesis should be
returned unused. This tag should not be detached from the bioprosthesis until
just prior to implantation.
Graspingtheplasticsleeve(Figure3)continuetherotationtoovercomethe
resistanceuntiltheholderpostreachestheunlockposition(Figure4aandFigure
4b).Applytherequiredpushforceonthehandleuntilthepostslidesacrossthe
leafletsandsnapsintoitsfullydeployedposition(Figure5).
Caution: If an adequate push force is not applied to the handle when deploying
the Tricentrix holder system, the tenting system will not be secured and will not
be able to prevent suture entrapment. Always check for proper deployment.
There should be no more space between the handle attachment adapter and
the clip. The handle/post assembly should not be able to slide any longer.
The holder post should protrude through the leaflets while the three (3)
commissures should deflect slightly towards the center of the bioprosthesis. The
leaflets will temporarily be wrinkled by the deployed holder post. When the
holder is removed following implantation, the leaflets will return to their
normal position.
After deployment, remove the sleeve by holding the handle and pulling the
sleeve off the clip (Figure 6). Remove the clip by sliding it off the holder in a
sideways direction (Figure 7). Both sleeve and clip should be discarded. Once the
handle has been attached, it should not be removed from the holder until the
bioprosthesis is seated to the annulus.
Rinse Procedure
Within the sterile operative field, prepare two rinse basins, each containing no
less than 500 ml of sterile, physiological saline solution. Place the deployed
bioprosthesis in the saline solution and make sure that it completely covers the
bioprosthesis and holder. Do not rinse with the sleeve and clip attached. With
the bioprosthesis and holder submerged, slowly agitate the basin or use the
attached handle to gently swirl the bioprosthesis back and forth for a minimum
of 1 minute in each of the two previously prepared rinse basins. The
bioprosthesis should remain in the second rinse basin until ready for
implantation.
Caution: Avoid contact of the leaflet tissue or the rinse solution with towels,
linens, or other sources of lint and particulate matter that may be transferred to
the leaflet tissue.
Caution: Do not allow the leaflet tissue to contact the bottom or sides of the
rinse basin.
Caution: Care must be taken to ensure that the serial number tag does not
come in contact with the leaflet tissue during rinsing.
Inspect the bioprosthesis and remove the serial number tag just prior to
implantation. Exercise care to avoid cutting or tearing the sewing ring cloth
during removal of the serial number tag.
11.5 Device Implantation
Because of the complexity and variation in the surgical procedure of cardiac
valve replacement, the choice of surgical technique is left to the discretion of the
individual surgeon. In general, the standard implantation technique includes:
1. Proper sizing; 2. Proper seating of the prosthesis; 3. Tying sutures with the
holder in place to avoid suture looping or chordal entrapment; 4. Examination of
the bioprosthetic leaflets for distortion or leak during tying.
Proper bioprosthesis size selection is an important part of mitral valve
replacement.
Verify that the sizers 1177HP have been sterilized according to the
recommended instructions in Section 11.3. If sterile, insert the 1111, 1117 or
1126 handle into the sizer and turn it clockwise until positive contact is felt
between the handle and sizer.
Caution:Adequateremovalofcalciumdepositsfromthepatient’sannulusmust
beperformedbeforeimplantationtoavoiddamagetothedelicatebioprosthesis
leaflettissueasaresultofcontactwithcalciumdeposits.
Insert the sizer into the mitral annulus. The sizer should always fit comfortably
in the annulus.
Warning: Care must always be exercised to avoid the use of too large a
prosthesis since oversizing may create damage or localized mechanical stresses,
which may in turn injure the heart or result in leaflet tissue failure, stent
distortion and regurgitation.
Caution: Only sizers 1177HP should be used during the selection of the
Carpentier-Edwards PERIMOUNT MAGNA mitral pericardial bioprosthesis model
7000TFX size; other sizers may result in improper valve selection. Sizers 1177HP
are marked for both size and EOA to provide clinically relevant information
during surgery and help avoid oversizing (see 11.2 Accessories).
6

Like other mitral bioprostheses, the Magna mitral bioprosthesis 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.
Sizing for implantation using non-everting mattress sutures:
Whenanon-evertingmattresssuturetechniqueisused,pledgetsaretypically
placedontheventricularaspectoftheannulus.Whensizing,thebarrelportionof
thesizerispassedthroughthemitralannulussothatthelipofthesizer,which
simulatesthesewingringportionofthebioprosthesis,restsonthesuperioraspect
oftheannulus.Oversizingofthebioprosthesisshouldbeavoided.
Subvalvular apparatus preservation sizing and implantation:
Chordal preservation techniques may decrease the size of valve that can be
implanted. With chordal sparing, the preserved leaflets are reefed within the
valve-sutures and compressed between the sewing ring and the native annulus,
thereby decreasing the size of the annulus (Ref. 8). When using these
techniques, it is recommended that the surgeon sizes the valve after sutures
have been placed to ensure that sizing is more accurate and to avoid placing too
large a bioprosthesis.
Caution: Special care must be exercised when using chordal preservation
techniques to avoid chordae entrapment by a strut.
Due to the elastic nature of a chord, it may be extended by the Tricentrix holder
system during implantation but retract back around the post once the holder is
removed, entrapping leaflets and impairing function. Sizers 1177HP are made of
a transparent material to allow visualization of the subvalvular apparatus
during sizing. Make sure no chord will be in the way of the struts.
Caution: Because of the intense temperature and lighting conditions
in the operating field, the bioprosthesis should be irrigated frequently
(every 1 to 2 minutes is recommended) on both sides with sterile
physiological saline to keep the valve moist during the implant
procedure.
Proper orientation of the bioprosthesis
Caution:ThewireformframeoftheMagnamitralbioprosthesisissymmetrical,
andthethreecommissuresupports(struts)areequallyspaced.However,the
sewingringisdesignedforaspecificorientationofthebioprosthesis.The
scallopedpartofthesewingring,betweenthetwosiliconeprotrusions,shouldbe
placedacrosstheintercommissuralanteriorportionoftheannulusandstraddle
theleftventricularoutflowtract.
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.
Firmtensionmustbemaintainedonthesuturesasthebioprosthesisislowered
intotheannulus;thispreventsformationofsutureloopsthatmightentrapa
leaflet.This,whencombinedwiththefullyretractedstentpostswhenthe
Tricentrixholdersystemisinplace,helpsguidethesuturesintotheircorrect
positionbehindthestrutsandontothesewingring.
Remove the handle prior to tying the sutures. The handle and 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 white adapter (Figure 8). Remove the adapter and handle
assembly as one unit.
Caution: Avoid looping or catching a suture around the open cages, free struts,
or commissure supports of the bioprosthesis, which would interfere with proper
valvular function. To avoid suture looping, it is essential to leave the deployed
holder in place until all knots are tied.
However, if leaving the holder in place obstructs the surgeon’s view, all the
sutures adjacent to each of the three frame struts must be tied down before
cutting the three holder attachment threads to remove the holder.
Caution: If the deployed holder attachment threads are cut before these
adjacent sutures are tied down, the holder can no longer prevent suture looping
around the frame struts.
Specialattentionmustbegiventoavoidtyingthesuturesontopofthecornersof
theholderlegs.Beforetyingeachsuture,examinetheleafletswhileholdingthe
twostrandsofthesutureundertension.Distortionormovementoftheleaflets
duringthismaneuversuggeststhatthesutureisloopedaroundastrut.Atno
pointbeforeorafterholderremovalshouldtensiononthesuturesbereleasedas
thismayfacilitateformationofloopsinthesuturesandpossibleentrapment.Itis
recommendedtoplaceasurgicalmirrorthroughtheleafletsaftertheholder
removalinordertoexamineeachstrutandpropersutureplacement.
Caution: When using interrupted sutures, it is important to cut the sutures
close to the knots and to ensure that exposed suture tails will not come into
contact with the leaflet tissue (Ref. 8).
The Tricentrix holder system is removed as a unit at the completion of the
suturing procedure as follows (Figure 9):
1. Cut each of the three (3) exposed sutures using a scalpel or scissor placed
only in the cutting channel. Never attempt to cut a suture below a partially
separated holder as a part of the attaching suture may fall in the ventricle.
Avoid cutting or damaging the stent or leaflet tissue when cutting the
sutures.
2. When all three (3) attaching sutures have been properly cut, remove the
Tricentrix holder system from the bioprosthesis as a unit, along with
attaching sutures, using sterile gloved hands or protected forceps.
3. Following surgery, remove the holder and discard.
11.6 Return of Explanted Bioprostheses
Edwards Lifesciences is interested in obtaining all recovered clinical specimens
of Carpentier-Edwards PERIMOUNT MAGNA mitral pericardial bioprostheses
model 7000TFX for analysis. A written report summarizing our findings will be
provided to the physician upon completion of our evaluation. Please contact
your local representative for return of recovered bioprostheses. The explanted
bioprostheses should be placed into a suitable histological fixative such as 10%
formalin or 2% glutaraldehyde immediately after excision and returned to the
company. Refrigeration is not necessary under these circumstances.
7

9
Table 1: Observed Adverse Event Rates for MVR and DVR
All patients analyzed: N = 363 Cumulative follow-up: 1100 patient-years
Early Events
Late Events1
Freedom from Event (%) [95% CI]2
Complication
n3
%
n
%/pt-yr
1 year (n = 287)
5 years (n = 141)
8 years (n = 18)
Mortality (all)
34
9.4
50
4.7
85.5 [81.8, 89.2]
75.4 [70.3, 80.6]
65.4 [57.6, 73.2]
Valve-related events
Mortality (valve-related)
0
0
16
1.5
97.7 [96.0, 99.4]
95.3 [92.8, 97.8]
91.9 [87.5, 96.4]
Explants
0
0
8
0.7
98.7 [98.0, 99.3]
96.7 [95.3, 98.0]
95.6 [93.9, 97.3]
Reoperations
2
0.6
12
1.1
97.1 [96.2, 98.1]
95.1 [93.6, 96.6]
93.0 [90.9, 95.1]
Anticoagulant-related
2
0.6
9
0.8
97.1 [95.2, 99.0]
97.1 [95.2, 99.0]
94.1 [88.2, 100]
hemorrhage
Endocarditis
1
0.3
3
0.3
99.0 [97.9, 100]
98.7 [97.4, 98.9]
98.7 [97.4, 98.9]
Hemolysis
0
0.0
1
0.1
99.7 [99.0, 100]
99.7 [99.0, 100]
99.7 [99.0, 100]
Nonstructural dysfunction
0
0.0
3
0.3
100 [100, 100]
99.3 [98.0, 100]
98.3 [95.9, 100]
Perivalvular leak (all)
1
0.3
5
0.5
98.4 [97.0, 99.8]
98.4 [97.0, 99.8]
97.3 [94.9, 99.8]
Structural valve
0
0.0
5
0.5
100.0 [100, 100]
97.6 [95.2, 100]
92.8 [85.3, 100]
deterioration
Thromboembolism
5
1.4
8
0.7
97.5 [95.8, 99.2]
96.1 [93.8, 98.5]
96.1 [93.8, 98.5]
Thrombosis
0
0.0
0
0.0
100.0 [100, 100]
100.0 [100, 100]
100.0 [100, 100]
Notes:
1.
Late event rates were calculated as linearized rates (%/pt-yr) based on 1072.5 late patient-years (> 30 days postoperatively).
2.
Freedom from event rates were calculated using the Kaplan-Meier method. Greenwood’s formula was used for calculation of the standard errors of these
estimates.
3.
n = number of events.
Table 2: Preoperative Patient Demographics
Study Characteristics (N = 363; 1100 total pt-yrs.)
Variable
Category
n
% (n/N)1
Age at implant
Mean ± SD
363
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 3: Operative Patient Demographics
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
Table 4: Effectiveness Outcomes, Functional NYHA
Preoperative
Postoperative Assessments
Assessment
1 to 2 Year
5 Year
NYHA Functional Class
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.
10

11
Table 5: Effective Outcomes, Hemodynamic Results1
Hemodynamic
Results By Valve Size
Parameter
25 mm
27 mm
29 mm
31 mm
33 mm
Discharge/Early Post-Implant (n = 130, 109 MVR2 and 21 DVR3)
Mean gradient4
n = 3
n = 23
n = 36
n = 23
n = 3
• mean ± sd
5.7 ± 1.2
4.2 ± 1.7
4.2 ± 1.7
3.6 ± 1.0
7.5 ± 5.8
• min, max
5, 7
2, 9
1, 8
2, 5
3, 14
EOA5
n = 1
n = 17
n = 22
n = 25
n = 5
• mean ± sd
1.5
2.9 ± 0.9
3.1 ± 0.9
2.5 ± 0.7
3.0 ± 1.2
• min, max
1.5, 1.5
1.3, 4.1
1.4, 4.2
1.5, 3.8
1.6, 4.9
Regurgitation6
n = 3
n = 28
n = 51
n = 40
n = 8
0
3/3 (100%)
22/28 (79%)
36/51 (71%)
30/40 (75%)
4/8 (50%)
1+
0/3 (0%)
5/28 (18%)
13/51 (25%)
7/40 (18%)
4/8 (50%)
2+
0/3 (0%)
0/28 (0%)
1/51 (2%)
3/40 (7%)
0/8 (0%)
3+
0/3 (0%)
0/28 (0%)
1/51 (2%)
0/40 (0%)
0/8 (0%)
4+
0/3 (0%)
0/28 (0%)
0/51 (0%)
0/40 (0%)
0/8 (0%)
Not available
0/3 (0%)
1/28 (3%)
0/51 (0%)
0/40 (0%)
0/8 (0%)
3 to 6 Month Post-Implant Interval (n = 49, 42 MVR2 and 7 DVR3)
Mean gradient4
n = 5
n = 19
n = 15
n = 5
n = 2
• mean ± sd
6.4 ± 1.7
5.3 ± 5
3.4 ± 1.2
4 ± 1.9
4 ± 0
• min, max
5, 9
2, 25
2, 6
2, 7
4, 4
EOA5
n = 5
n = 18
n = 13
n = 5
n = 2
• mean ± sd
2.9 ± 0.8
2.6 ± 0.7
2.8 ± 0.6
2.9 ± 0.3
2.6 ± 1
• min, max
1.8, 3.6
1.5, 5
2, 3.8
2.4, 3.3
2, 3.3
Regurgitation6
n = 5
n = 21
n = 15
n = 6
n = 2
0
3/5 (60%)
17/21 (81%)
6/15 (40%)
4/6 (67%)
1/2 (50%)
1+
0/5 (0%)
4/21 (19%)
8/15 (53%)
2/6 (33%)
0/2 (0%)
2+
1/5 (20%)
0/21 (0%)
1/15 (7%)
0/6 (0%)
1/2 (50%)
3+
0/5 (0%)
0/21 (0%)
0/15 (0%)
0/6 (0%)
0/2 (0%)
4+
1/5 (20%)
0/21 (0%)
0/15 (0%)
0/6 (0%)
0/2 (0%)
Not available
0/5 (0%)
0/21 (0%)
0/15 (0%)
0/6 (0%)
0/2 (0%)
1 to 2 Year Post-Implant Interval (n = 131, 114 MVR2 and 17 DVR3)
Mean gradient4
n = 3
n = 40
n = 47
n = 27
n = 4
• mean ± sd
5.2 ± 0.7
4.1 ± 1.6
3.5 ± 1.8
3.1 ± 1.4
2.1 ± 0.5
• min, max
4.7, 6
1, 7
1, 10
1, 7
1.5, 2.7
EOA5
n = 2
n = 35
n = 46
n = 29
n = 5
• mean ± sd
1.8 ± 0.4
2.3 ± 0.6
2.6 ± 0.5
2.6 ± 0.7
2.5 ± 0.5
• min, max
1.5, 2.0
1.2, 3.5
1.1, 3.7
1.1, 3.7
2.1, 3.2
Regurgitation6
n = 4
n = 42
n = 51
n = 29
n = 5
0
2/4 (50%)
31/42 (74%)
36/51 (71%)
17/29 (59%)
3/5 (60%)
1+
1/4 (25%)
9/42 (21%)
11/51 (21%)
8/29 (27%)
1/5 (20%)
2+
1/4 (25%)
2/42 (5%)
4/51 (8%)
2/29 (7%)
1/5 (20%)
3+
0/4 (0%)
0/42 (0%)
0/51 (0%)
2/29 (7%)
0/5 (0%)
4+
0/4 (0%)
0/42 (0%)
0/51 (0%)
0/29 (0%)
0/5 (0%)
Not available
0/4 (0%)
0/42 (0%)
0/51 (0%)
0/29 (0%)
0/5 (0%)
continued on following page

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
DO NOT RESTERILIZE THE BIOPROSTHESIS BY ANY METHOD. Exposure of
the bioprosthesis or container 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. 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 monitor the temperature that the device is
exposed to during transit and storage. If the indicator displays any
reading other than “OK” do not use the bioprosthesis. Please refer to
Packaging section (10.2) for further instructions.
DO NOT USE the bioprosthesis if the tamper evident seal on the jar is
broken.
DO NOT USE the bioprosthesis if expiration date has elapsed.
DO NOT USE the bioprosthesis if the container is leaking, damaged, or
the glutaraldehyde solution does not completely cover the
bioprosthesis.
DO NOT EXPOSE the bioprosthesis to any solutions, chemicals,
antibiotics, etc., except for the storage solution or sterile physiological
saline solution. Irreparable damage to the leaflet tissue, which may
not be apparent under visual inspection, may result.
DO NOT ALLOW the bioprosthesis to dry. It must be kept moist at all
times. Maintain tissue moisture with sterile physiological saline
irrigation on both sides of the leaflet tissue.
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.
DO NOT USE the bioprosthesis if it has been dropped, damaged, or
mishandled in any way. Should a bioprosthesis be damaged during
insertion, do not attempt repair.
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.
Clinical data that establish the safety and efficacy of the bioprosthesis for use in
patients under the age of 20 are not available; therefore, we recommend careful
consideration of its use in younger patients.
As with any implanted medical device, there is a potential for patient
immunological response (see device description for materials).
The decision to use a bioprosthesis must ultimately be made by the surgeon on
an individual basis after a careful evaluation of the short- and long-term risks
and benefits to the patient and consideration of alternative methods of
treatment.
Long-term durability has not been established for bioprostheses. Serious
adverse events, sometimes leading to replacement of the bioprosthesis and/or
death, may be associated with the use of prosthetic valves (see 6. Adverse
Events). A full explanation of the benefits and risks should be given to each
prospective patient before surgery.
Note: Bioprostheses should be used with caution in the presence of severe
systemic hypertension or when the anticipated patient longevity is longer than
the known longevity of the prosthesis (see 7. Clinical Studies).
Careful and continuous 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.
Recipients of prosthetic heart valves who are undergoing dental procedures
should receive prophylactic antibiotic therapy to minimize the possibility of
prosthetic infection. Bioprosthetic heart valve recipients should be maintained
on anticoagulant therapy (except where contraindicated) during the initial
healing stages after implantation, approximately 2 to 3 months. Anticoagulants
should then be discontinued over a period of 10 days, except in those patients
for whom indefinite anticoagulant protection is indicated, i.e., in the absence of
sinus rhythm and in patients with a dilated left atrium, calcification of the atrial
wall, or history of previous atrial thrombus. However, the appropriate
anticoagulation therapy must be determined by the physician on an individual
basis (Ref. 7).
Adequate rinsing with physiological saline is mandatory before implantation to
reduce the glutaraldehyde concentration (see 11.4 Handling and
Preparation Instructions). No other solutions, drugs, chemicals, antibiotics,
etc., should ever be added to the glutaraldehyde or rinse solutions, as
irreparable damage to the leaflet tissue, which may not be apparent under
visual inspection, may result.
5. Precautions
•
Do not sterilize the sizer models 1171B, 1171R, and handle models 1111,
1117, or 1172 in their shipping containers.
•
Use only the sterilization tray provided in model SET1171 to sterilize the
sizers and the handles.
•
The outside of the jar is not sterile and must not be placed in the sterile
field.
•
To avoid contamination, it is strongly recommended that the jar of a
Carpentier-Edwards PERIMOUNT Magna Mitral Ease pericardial
bioprosthesis model 7200TFX not be opened unless implantation is certain.
•
Adequate rinsing with physiological saline must be performed before
implantation to reduce the glutaraldehyde concentration.
•
Avoid contact of the leaflet tissue or the rinse solution with towels, linens,
or other sources of lint and particulate matter that may be transferred to the
leaflet tissue.
•
Do not allow the leaflet tissue to contact the bottom or sides of the rinse
basin.
•
Glutaraldehyde may cause irritation of the skin, eyes, nose, and throat.
Avoid prolonged or repeated exposure or breathing of the solution. Use only
2

3
with adequate ventilation. If skin contact occurs, immediately flush the
affected area with water; in the event of contact with the eyes, seek
immediate medical attention. For more information about glutaraldehyde
exposure, please refer to the Material Safety Data Sheet available from
Edwards Lifesciences.
•
Always deploy the Tricentrix holder system fully to minimize the risk of
suture entrapment. It will snap into a secured and locked position.
•
A serial number tag is attached to the sewing ring of each bioprosthesis by a
suture. This serial number should be checked against the number on the jar
and implantation data card; if any difference is noted, the bioprosthesis
should be returned unused. Care must be taken to ensure that the serial
number tag does not come in contact with the leaflet tissue during rinsing.
Inspection of the bioprosthesis and removal of the serial number tag should
be performed just prior to implantation. Care should be exercised to avoid
cutting or tearing the sewing ring cloth during removal of the serial number
tag.
•
Careful handling is required for all implantable devices. If the bioprosthesis
is dropped, damaged, or mishandled in any way, it must not be used for
human implantation.
•
To avoid damage to the delicate bioprosthetic leaflet tissue, as a result of
contact with calcium deposits, adequate removal of calcium deposits from
the patient’s annulus must be performed before implantation.
•
Handle the bioprosthesis only with Edwards Lifesciences accessories. Only
Edwards Lifesciences sizers model 1171B or 1171R should be used during
the selection of the Magna Mitral Ease bioprosthesis size; other sizers may
result in improper bioprosthesis selection.
•
Oversizing must be especially avoided as it may cause bioprosthesis damage
or localized mechanical stresses, which may in turn injure the heart or result
in leaflet tissue failure, stent distortion and regurgitation.
•
Special care must be exercised when using chordal preservation techniques
to avoid chordae entrapment by a strut.
•
Due to the relative flexibility of the frame, care must be exercised to prevent
folding or deformation of the stent.
•
The surgeon should be familiar with the recommendations for proper sizing
and placement of the bioprosthesis according to the suture technique used
(see 11.5 Device Implantation).
•
The sewing ring is designed for a specific orientation: the scalloped part of
the sewing ring, between the black suture markers, should be placed across
the intercommissural anterior portion of the annulus and straddle the left
ventricular outflow tract.
•
Special care must be exercised to avoid placing a strut in front of the left
ventricular outflow tract, as this may impair the long-term hemodynamic
performance.
•
As with all prostheses that have open cages, free struts, or commissure
supports, care must be exercised to avoid looping or catching a suture
around a commissure, which would interfere with proper valvular function.
To avoid suture looping, it is essential to leave the deployed holder in place
until all knots are tied.
•
If the deployed holder attachment threads are cut, before at least all the
sutures adjacent to the struts are tied down, the holder can no longer
prevent suture looping.
•
When using interrupted sutures, it is important to cut the sutures close to
the knots and to ensure that exposed suture tails will not come into contact
with the leaflet tissue.
6. Adverse Events
6.1 Observed Adverse Events
The Carpentier-Edwards PERIMOUNT Magna Mitral Ease pericardial
bioprosthesis model 7200TFX uses the same wireform frame and leaflet
attachment as Edwards Lifesciences pericardial mitral bioprostheses models
6900, 6900P, 6900PTFX, and 7000TFX. 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 1 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. 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 2 and 3. Effectiveness results are presented in Tables 4 and 5.
6.2 Potential Adverse Events
Adverse events potentially associated with the use of bioprosthetic heart valves
include:
•
Angina
•
Cardiac arrhythmias
•
Endocarditis
•
Heart failure
•
Hemolysis
•
Hemolytic anemia
•
Hemorrhage
•
Myocardial infarction
•
Prosthesis leaflet entrapment
•
Prosthesis nonstructural dysfunction
•
Prosthesis pannus
•
Prosthesis perivalvular leak
•
Prosthesis regurgitation
•
Prosthesis structural deterioration
•
Prosthesis thrombosis
•
Stroke

•
Thromboembolism
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.
7. Clinical Studies
The safety endpoints captured in the prospective studies were complications;
blood analyses were used to confirm the absence or presence of certain
complications. The safety results are provided in Table 1. Effectiveness
endpoints were New York Heart Association (NYHA) functional classification and
echocardiographic assessments. Preoperative and operative patient
demographics are presented, followed by the effectiveness results. There are no
clinical data presently available demonstrating increased resistance of the
Carpentier-Edwards PERIMOUNT Magna Mitral Ease pericardial bioprosthesis
model 7200TFX to calcification as compared to other commercially available
bioprostheses.
8. 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 a dilated left atrium, a history of thrombotic events, an absence of sinus
rhythm, calcification of the atrial wall, or with atrial fibrillation or flutter. The
decision to use a bioprosthesis must ultimately be made by the physician on an
individual basis after a careful evaluation of the short-term and long-term risks
and benefits to the patient and consideration of alternative methods of
treatment (Ref. 7).
8.1 Specific Patient Populations
The safety and effectiveness of the Carpentier-Edwards PERIMOUNT
Magna Mitral Ease pericardial bioprosthesis model 7200TFX 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, or young adults.
9. Patient Counseling Information
Careful and continued medical follow-up (at least by an annual visit to the
physician) is advised so that valve-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 Implantation Data Card at all times
and to inform their healthcare providers that they have a mitral bioprosthetic
implant when seeking care.
10. How Supplied
10.1 Available Models and Sizes
The Carpentier-Edwards PERIMOUNT Magna Mitral Ease pericardial
bioprosthesis model 7200TFX is available in labeled sizes 27, 29, 31, 33, and 35
(see Figure 1 for nominal specifications).
10.2 Packaging
The Magna Mitral Ease bioprosthesis is provided sterile and nonpyrogenic
packaged in glutaraldehyde, in a plastic jar to which a seal has been applied.
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 monitor the temperature that the device is exposed to during
transit and storage. Upon receipt of the bioprosthesis immediately inspect to
see if the indicator displays any reading other than “OK”, if so do not use the
bioprosthesis. Contact the local supplier or Edwards Lifesciences representative
to make arrangements for return, authorization and replacement. Any
bioprosthesis returned to Edwards Lifesciences must be shipped in its original
packaging in which it was received.
Warning: The bioprosthesis must be carefully inspected before
implantation for evidence of extreme temperature exposure or other
damage.
Due to the biological nature of this bioprosthesis and its sensitivity to physical
handling and environmental conditions, it cannot be returned, except as noted
above.
Note: Products found to have been subjected to freezing or excessive heat later
than 3 days following receipt will be considered to have resulted from
environmental conditions within the control of the customer, and subject to
replacement at customer’s expense.
10.3 Storage
The Magna Mitral Ease bioprosthesis should be stored at 10 °C to 25 °C
(50-77 °F). Stock inspection and rotation at regular intervals are recommended
to ensure that the bioprostheses are used before the expiration date stamped on
the package label.
Warning: Do not freeze. Always store bioprostheses in a dry,
contamination-free area. Any bioprosthesis that has been frozen, or is
suspected of having been frozen, should not be used for human
implantation.
4

11. Directions for Use
11.1 Physician Training
No special training is required to implant the Carpentier-Edwards PERIMOUNT
Magna Mitral Ease bioprosthesis model 7200TFX. The techniques for implanting
this bioprosthesis are similar to those for implanting any stented mitral
bioprostheses.
11.2 Accessories
Accessories available for use with the Magna Mitral Ease bioprosthesis are:
•
Tricentrix holder system
•
Replica Sizer 1171R (Figure 10)
•
Barrel Sizer 1171B (Figure 11)
•
Sterilization Tray provided in model SET1171
•
Flexible Handle models 1111, 1117, 1172, and 1126 (single use) (Figure 13)
All accessories are supplied non-sterile, except for the Tricentrix holder system
that is supplied sterile attached to the sterile bioprosthesis and the handle 1126
that is supplied sterile and is for single use only.
Sizers and Tray
Only sizers model 1171B or 1171R may be used with the Magna Mitral Ease
bioprosthesis.
Caution: Do not use other manufacturer’s valve sizers, or sizers for other
Edwards Lifesciences valve prostheses to size the Magna Mitral Ease
bioprosthesis.
Use only the sizers model 1171B or 1171R to determine the appropriate
Magna Mitral Ease bioprosthesis size. Sizers model 1171B and 1171R permit
direct observation of their fit within the annulus and are provided for each
available Magna Mitral Ease bioprosthesis size. The barrel of the sizers model
1171B and 1171R indicate the external stent diameter at the base (Figure 1).
The lip of the replica sizer 1171R 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 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 1171R to aid in
assessing optimal alignment and seating.
The sizers include preattached 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 1171B and 1171R are labeled with the
bioprosthesis size.
Tricentrix Holder System and Handles
The holder/handle assembly consists of two (2) components: the Tricentrix
holder system that is mounted to the Magna Mitral Ease bioprosthesis, and a
handle (1111, 1117, 1172, or 1126) that is attached to the Tricentrix holder
system at the time of surgery (Figure 2).
The following handles (Figure 13) may be used with the Magna Mitral Ease
bioprosthesis:
•
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.
•
Handle 1172 has been designed to improve access in the case of difficult
exposure, a deep thoracic cage, or in minimally invasive procedures.
The Tricentrix holder has short legs and beveled edges to increase suturing
space and ease knot tying (Figure 14).
11.3 Accessory Sterilization
The 1126 handle is provided sterile and is intended for single use only. The
handles 1111, 1117, and 1172 and the sizers 1171B and 1171R are supplied
non-sterile and must be cleaned and sterilized before using. The handles 1111,
1117, and 1172 must be disassembled from any accessories prior to cleaning
and sterilization.
Caution: Examine sizers and handles for signs of wear, such as dullness,
cracking, or crazing. Replace sizer or handle if any deterioration is observed.
Caution: Do not sterilize the sizers and handles 1111, 1117, or 1172 in their
shipping containers.
Use only the sterilization tray provided in model SET1171 to sterilize the sizers
and the handles.
The accessories can be sterilized using the following recommended autoclave
sterilization methods:
I. Gravity Displacement:
a) Wrapped:
Temperature:
270-279 °F (132-137 °C)
Exposure Time:
10-18 minutes
b) Unwrapped (“flash”):
Temperature:
270-279 °F (132-137 °C)
Exposure Time:
3 minutes
II. Prevacuum:
a) Wrapped:
Temperature:
270-279 °F (132-137 °C)
Exposure Time:
3-18 minutes
b) Unwrapped (“flash”):
Temperature:
270-279 °F (132-137 °C)
Exposure Time:
3 minutes
Each institution should use procedures that include biological indicators to
determine the effectiveness of the sterilization procedure.
5
Model
Shaft
Material
Overall Length (inches)
inch
cm
Reusable
1111
Stainless steel
7.0
17.8
Yes
1117
Nitinol
9.1
23.2
Yes
1126
Stainless steel
11.5
29.2
No
1172
Nitinol
11.3
28.6
Yes

11.4 Handling and Preparation Instructions
The bioprosthesis is packaged sterile in a plastic jar with a screw-cap closure and
seal. Before opening, carefully examine the jar for evidence of damage (e.g., a
cracked jar or lid), leakage, or broken or missing seals. Remove the seal and turn
the lid counter-clockwise to open the container. The bioprosthesis and Tricentrix
holder system within the container are sterile.
Caution: The outside of the jar is not sterile and must not be placed in
the sterile field. The contents of the jar should be handled in an aseptic
manner to prevent contamination.
Caution: Bioprostheses from containers found to be damaged, leaking,
without adequate glutaraldehyde, or missing intact seals must not be
used for human implantation.
Caution: It is strongly recommended that the jar of a
Magna Mitral Ease bioprosthesis not be opened unless implantation is
certain. This is necessary to reduce the risk of contamination, because
it has been established that glutaraldehyde alone is not a 100%
effective sterilant against all possible contaminants.
Warning: No attempt should be made to resterilize a
Magna Mitral Ease bioprosthesis.
Warning: Do not use the bioprosthesis if it has been dropped, damaged, or
mishandled in any way. Should a bioprosthesis be damaged during insertion, do
not attempt repair.
Warning: Do not grasp the leaflet tissue portion 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 bioprosthesis function.
Verify that the handle, model 1111,1117, or 1172, has been sterilized according
to the instructions provided in Section 11.3. Attach the handle to the Tricentrix
holder system and turn it clockwise until a positive resistance is felt then remove
the whole assembly (i.e., plastic sleeve, clip, the Tricentrix holder system and
bioprosthesis) from the jar.
A tag with a serial number is attached to the sewing ring of each bioprosthesis
by a suture. This serial number should be checked against the number on the jar
and implantation card; if any differences are noted, the bioprosthesis should be
returned unused. This tag should not be detached from the bioprosthesis until
just prior to implantation.
Grasping the plastic sleeve (Figure 3) continue the rotation to overcome the
resistance until the holder post reaches the unlock position (Figure 4a and
Figure 4b). Apply the required push force on the handle until the post slides
across the leaflets and snaps into its fully deployed position (Figure 5).
Caution: If an adequate push force is not applied to the handle when deploying
the Tricentrix holder system, the tenting system will not be secured and will not
be able to prevent suture entrapment. Always check for proper deployment.
There should be no more space between the handle attachment adapter and
the clip. The handle/post assembly should not be able to slide any longer.
The holder post should protrude through the leaflets while the three (3)
commissures should deflect slightly towards the center of the bioprosthesis. The
leaflets will temporarily be wrinkled by the deployed holder post. When the
holder is removed following implantation, the leaflets will return to their
normal position.
After deployment, remove the sleeve by holding the handle and pulling the
sleeve off the clip (Figure 6). Remove the clip by sliding it off the holder in a
sideways direction (Figure 7). Both sleeve and clip should be discarded. Once the
handle has been attached, it should not be removed from the holder until the
bioprosthesis is seated to the annulus.
Rinse Procedure
Within the sterile operative field, prepare two rinse basins, each containing no
less than 500 ml of sterile, physiological saline solution. Place the deployed
bioprosthesis in the saline solution and make sure that it completely covers the
bioprosthesis and holder. Do not rinse with the sleeve and clip attached. With
the bioprosthesis and holder submerged, slowly agitate the basin or use the
attached handle to gently swirl the bioprosthesis back and forth for a minimum
of 1 minute in each of the two previously prepared rinse basins. The
bioprosthesis should remain in the second rinse basin until ready for
implantation.
Caution: Avoid contact of the leaflet tissue or the rinse solution with towels,
linens, or other sources of lint and particulate matter that may be transferred to
the leaflet tissue.
Caution: Do not allow the leaflet tissue to contact the bottom or sides of the
rinse basin.
Caution: Care must be taken to ensure that the serial number tag does not
come in contact with the leaflet tissue during rinsing.
Inspect the bioprosthesis and remove the serial number tag just prior to
implantation. Exercise care to avoid cutting or tearing the sewing ring cloth
during removal of the serial number tag.
11.5 Device Implantation
Because of the complexity and variation in the surgical procedure of cardiac
valve replacement, the choice of surgical technique is left to the discretion of the
individual surgeon. In general, the standard implantation technique includes:
1. Proper sizing; 2. Proper seating of the prosthesis; 3. Tying sutures with the
holder in place to avoid suture looping or chordal entrapment; 4. Examination of
the bioprosthetic leaflets for distortion or leak during tying.
Proper bioprosthesis size selection is an important part of mitral valve
replacement.
Verify that the sizers 1171B and 1171R have been sterilized according to the
recommended instructions in Section 11.3.
Caution: Examine sizers and handles for signs of wear, such as dullness,
cracking, or crazing. Do not use sizer or handle if any deterioration is observed.
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.
Warning: Care must always be exercised to avoid the use of too large a
prosthesis since oversizing may create damage or localized mechanical stresses,
which may in turn injure the heart or result in leaflet tissue failure, stent
distortion and regurgitation.
Caution: Use only sizers 1171B or 1171R during the selection of the
Magna Mitral Ease bioprosthesis size; other sizers may result in improper valve
selection (see 11.2 Accessories).
Like other mitral bioprostheses, the Magna Mitral Ease bioprosthesis is usually
implanted using pledgeted mattress sutures. It is recommended to size the
6

annulus after the sutures have been placed, as sutures may decrease the size of
the bioprosthesis that can be implanted.
Sizing for implantation:
Sizing with barrel sizer 1171B: To size with barrel sizer 1171B, pass the barrel
portion of the sizer through the mitral annulus.
Sizing with replica sizer 1171R: To size with replica sizer 1171R, pass the barrel
portion of the sizer through the mitral annulus so that the lip of the sizer, which
simulates the sewing ring portion of the bioprosthesis, rests on the superior
aspect of the annulus (Figure 12).
Some techniques such as use of pledgets, leaflet reefing, or mitral subvalvular
apparatus preservation may further reduce the size of the mitral annulus which
can result in the need for a smaller bioprosthesis to be implanted (Ref. 8). When
using these techniques, it is recommended to re-size the annulus to avoid
oversizing of the bioprosthesis. The consistent performance of the PERIMOUNT
mitral bioprostheses makes oversizing unnecessary to achieve the desired
hemodynamic performance in most patients (Table 5).
Due to the elastic nature of a chord, it may be extended by the Tricentrix holder
system during implantation but retract back around the post once the holder is
removed, entrapping leaflets and impairing function. Sizers 1171B and 1171R
are made of a transparent material to allow visualization of the subvalvular
apparatus during sizing. Make sure no chord will be in the way of the struts.
Caution: Exercise special care when using subvalvular apparatus preservation
techniques to avoid chordae entrapment by a strut.
Warning: Avoid oversizing the bioprosthesis. 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 regurgitation.
Caution: Because of the intense temperature and lighting conditions
in the operating field, the bioprosthesis should be irrigated frequently
(every 1 to 2 minutes is recommended) on both sides with sterile
physiological saline to keep the valve moist during the implant
procedure.
Proper orientation of the bioprosthesis
Caution: The wireform frame of the Magna Mitral Ease 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.
When placing sutures through the sewing ring, sliding drag forces are reduced
when sutures are placed straight through the middle to outer portion of the
sewing ring. Irrigation with saline can further reduce suture drag forces.
Firm tension must be maintained on the sutures as the bioprosthesis is lowered
into the annulus; this prevents 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 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 cut the green
thread on the white adapter (Figure 8). Remove the adapter and handle
assembly as one unit.
Caution: Avoid looping or catching a suture around the open cages, free struts,
or commissure supports of the bioprosthesis, which would interfere with proper
valvular function. To avoid suture looping, it is essential to leave the deployed
holder in place until all knots are tied.
However, if leaving the holder in place obstructs the surgeon’s view, all the
sutures adjacent to each of the three frame struts must be tied down before
cutting the three holder attachment threads to remove the holder.
Caution: If the deployed holder attachment threads are cut before these
adjacent sutures are tied down, the holder can no longer prevent suture looping
around the frame struts.
Special attention must be given to avoid tying the sutures on top of the corners
of the holder legs. Before tying each suture, examine the leaflets while holding
the two strands of the suture under tension. Distortion or movement of the
leaflets during this maneuver suggests that the suture is looped around a strut.
At no point before or after holder removal should tension on the sutures be
released as this may facilitate formation of loops in the sutures and possible
entrapment. It is recommended to place a surgical mirror through the leaflets
after the holder removal in order to examine each strut and proper suture
placement.
Caution: When using interrupted sutures, it is important to cut the sutures
close to the knots and to ensure that exposed suture tails will not come into
contact with the leaflet tissue (Ref. 8).
The Tricentrix holder system is removed as a unit at the completion of the
suturing procedure as follows (Figure 9):
1. Cut each of the three (3) exposed sutures using a scalpel or scissor placed
only in the cutting channel. Never attempt to cut a suture below a partially
separated holder as a part of the attaching suture may fall in the ventricle.
Avoid cutting or damaging the stent or leaflet tissue when cutting the
sutures.
2. When all three (3) attaching sutures have been properly cut, remove the
Tricentrix holder system from the bioprosthesis as a unit, along with
attaching sutures, using sterile gloved hands or protected forceps.
3. Following surgery, remove the holder and discard.
11.6 Return of Explanted Bioprostheses
Edwards Lifesciences is interested in obtaining all recovered clinical specimens
of Carpentier-Edwards PERIMOUNT Magna Mitral Ease pericardial bioprostheses
model 7200TFX for analysis. A written report summarizing our findings will be
provided to the physician upon completion of our evaluation. Please contact
7

9
Table 1: Observed Adverse Event Rates for MVR and DVR
All patients analyzed: N = 363 Cumulative follow-up: 1100 patient-years
Early Events
Late Events1
Freedom from Event (%) [95% CI]2
Complication
n3
%
n
%/pt-yr
1 year (n = 287)
5 years (n = 141)
8 years (n = 18)
Mortality (all)
34
9.4
50
4.7
85.5 [81.8, 89.2]
75.4 [70.3, 80.6]
65.4 [57.6, 73.2]
Valve-related events
Mortality (valve-related)
0
0
16
1.5
97.7 [96.0, 99.4]
95.3 [92.8, 97.8]
91.9 [87.5, 96.4]
Explants
0
0
8
0.7
98.7 [98.0, 99.3]
96.7 [95.3, 98.0]
95.6 [93.9, 97.3]
Reoperations
2
0.6
12
1.1
97.1 [96.2, 98.1]
95.1 [93.6, 96.6]
93.0 [90.9, 95.1]
Anticoagulant-related
2
0.6
9
0.8
97.1 [95.2, 99.0]
97.1 [95.2, 99.0]
94.1 [88.2, 100]
hemorrhage
Endocarditis
1
0.3
3
0.3
99.0 [97.9, 100]
98.7 [97.4, 98.9]
98.7 [97.4, 98.9]
Hemolysis
0
0.0
1
0.1
99.7 [99.0, 100]
99.7 [99.0, 100]
99.7 [99.0, 100]
Nonstructural dysfunction
0
0.0
3
0.3
100 [100, 100]
99.3 [98.0, 100]
98.3 [95.9, 100]
Perivalvular leak (all)
1
0.3
5
0.5
98.4 [97.0, 99.8]
98.4 [97.0, 99.8]
97.3 [94.9, 99.8]
Structural valve
0
0.0
5
0.5
100.0 [100, 100]
97.6 [95.2, 100]
92.8 [85.3, 100]
deterioration
Thromboembolism
5
1.4
8
0.7
97.5 [95.8, 99.2]
96.1 [93.8, 98.5]
96.1 [93.8, 98.5]
Thrombosis
0
0.0
0
0.0
100.0 [100, 100]
100.0 [100, 100]
100.0 [100, 100]
Notes:
1.
Late event rates were calculated as linearized rates (%/pt-yr) based on 1072.5 late patient-years (> 30 days postoperatively).
2.
Freedom from event rates were calculated using the Kaplan-Meier method. Greenwood’s formula was used for calculation of the standard errors of these
estimates.
3.
n = number of events.
Table 2: Preoperative Patient Demographics
Study Characteristics (N = 363; 1100 total pt-yrs.)
Variable
Category
n
% (n/N)1
Age at implant
Mean ± SD
363
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 3: Operative Patient Demographics
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)7
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
7.
Refer to Table 6 to correlate the model 7200TFX sizes to these data.
Table 4: Effectiveness Outcomes, Functional NYHA
Preoperative
Postoperative Assessments
Assessment
1 to 2 Year
5 Year
NYHA Functional Class
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.
10

11
Table 5: Effective Outcomes, Hemodynamic Results1
Hemodynamic
Results By Valve Size7
Parameter
25 mm
27 mm
29 mm
31 mm
33 mm
Discharge/Early Post-Implant (n = 130, 109 MVR2 and 21 DVR3)
Mean gradient4
n = 3
n = 23
n = 36
n = 23
n = 3
• mean ± sd
5.7 ± 1.2
4.2 ± 1.7
4.2 ± 1.7
3.6 ± 1.0
7.5 ± 5.8
• min, max
5, 7
2, 9
1, 8
2, 5
3, 14
EOA5
n = 1
n = 17
n = 22
n = 25
n = 5
• mean ± sd
1.5
2.9 ± 0.9
3.1 ± 0.9
2.5 ± 0.7
3.0 ± 1.2
• min, max
1.5, 1.5
1.3, 4.1
1.4, 4.2
1.5, 3.8
1.6, 4.9
Regurgitation6
n = 3
n = 28
n = 51
n = 40
n = 8
0
3/3 (100%)
22/28 (79%)
36/51 (71%)
30/40 (75%)
4/8 (50%)
1+
0/3 (0%)
5/28 (18%)
13/51 (25%)
7/40 (18%)
4/8 (50%)
2+
0/3 (0%)
0/28 (0%)
1/51 (2%)
3/40 (7%)
0/8 (0%)
3+
0/3 (0%)
0/28 (0%)
1/51 (2%)
0/40 (0%)
0/8 (0%)
4+
0/3 (0%)
0/28 (0%)
0/51 (0%)
0/40 (0%)
0/8 (0%)
Not available
0/3 (0%)
1/28 (3%)
0/51 (0%)
0/40 (0%)
0/8 (0%)
3 to 6 Month Post-Implant Interval (n = 49, 42 MVR2 and 7 DVR3)
Mean gradient4
n = 5
n = 19
n = 15
n = 5
n = 2
• mean ± sd
6.4 ± 1.7
5.3 ± 5
3.4 ± 1.2
4 ± 1.9
4 ± 0
• min, max
5, 9
2, 25
2, 6
2, 7
4, 4
EOA5
n = 5
n = 18
n = 13
n = 5
n = 2
• mean ± sd
2.9 ± 0.8
2.6 ± 0.7
2.8 ± 0.6
2.9 ± 0.3
2.6 ± 1
• min, max
1.8, 3.6
1.5, 5
2, 3.8
2.4, 3.3
2, 3.3
Regurgitation6
n = 5
n = 21
n = 15
n = 6
n = 2
0
3/5 (60%)
17/21 (81%)
6/15 (40%)
4/6 (67%)
1/2 (50%)
1+
0/5 (0%)
4/21 (19%)
8/15 (53%)
2/6 (33%)
0/2 (0%)
2+
1/5 (20%)
0/21 (0%)
1/15 (7%)
0/6 (0%)
1/2 (50%)
3+
0/5 (0%)
0/21 (0%)
0/15 (0%)
0/6 (0%)
0/2 (0%)
4+
1/5 (20%)
0/21 (0%)
0/15 (0%)
0/6 (0%)
0/2 (0%)
Not available
0/5 (0%)
0/21 (0%)
0/15 (0%)
0/6 (0%)
0/2 (0%)
1 to 2 Year Post-Implant Interval (n = 131, 114 MVR2 and 17 DVR3)
Mean gradient4
n = 3
n = 40
n = 47
n = 27
n = 4
• mean ± sd
5.2 ± 0.7
4.1 ± 1.6
3.5 ± 1.8
3.1 ± 1.4
2.1 ± 0.5
• min, max
4.7, 6
1, 7
1, 10
1, 7
1.5, 2.7
EOA5
n = 2
n = 35
n = 46
n = 29
n = 5
• mean ± sd
1.8 ± 0.4
2.3 ± 0.6
2.6 ± 0.5
2.6 ± 0.7
2.5 ± 0.5
• min, max
1.5, 2.0
1.2, 3.5
1.1, 3.7
1.1, 3.7
2.1, 3.2
Regurgitation6
n = 4
n = 42
n = 51
n = 29
n = 5
0
2/4 (50%)
31/42 (74%)
36/51 (71%)
17/29 (59%)
3/5 (60%)
1+
1/4 (25%)
9/42 (21%)
11/51 (21%)
8/29 (27%)
1/5 (20%)
2+
1/4 (25%)
2/42 (5%)
4/51 (8%)
2/29 (7%)
1/5 (20%)
3+
0/4 (0%)
0/42 (0%)
0/51 (0%)
2/29 (7%)
0/5 (0%)
4+
0/4 (0%)
0/42 (0%)
0/51 (0%)
0/29 (0%)
0/5 (0%)
Not available
0/4 (0%)
0/42 (0%)
0/51 (0%)
0/29 (0%)
0/5 (0%)
continued on following page

•
Maximum MR system-reported whole-body-averaged
specific absorption rate (SAR) of 3W/kg for 15 minutes
of scanning.
In non-clinical testing, the Magna Mitral Ease bioprosthesis
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 Magna Mitral Ease bioprosthesis. Optimization of MR
imaging parameters is recommended.
Prices subject to change without notice.This product is
manufactured and sold under one or more of the following
US patents: US-Patent Nos. 5,928,281; 5,931,969;
5,961,549; 6,102,944; 6,210,957; 6,214,054; 6,245,105;
6,378,221; 6,409,758; 6,413,275; 6,416,547; 6,547,827;
6,553,681; 6,561,970; 6,585,766; 6,837,902; 6,878,168;
6,945,997; 6,966,925; 7,214,344; 7,658,763; 7,682,391;
RE 40570; and corresponding foreign patents. Additional
patents are pending.
References
1.
Marchand MA., et al. Fifteen-year Experience with the
Mitral Carpentier-Edwards PERIMOUNT Pericardial
Bioprosthesis. AnnThoracSurg. 2001; 71:S236-9.
2.
Liao K., et al. Bovine Pericardium versus Porcine Aortic
Valve: Comparison ofTissue Biological Properties As
ProstheticValves; ArtificialOrgans. 1992;16(4):361-5.
3.
Vesely I., et al. Comparison of the Compressive Buckling
of Porcine AorticValve Cusps and Bovine Pericardium. J.
HeartValveDis. January 1998; 7(1):34-9.
4.
Carpentier A. FromValvular Xenograft toValvular
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.MedDentSci. 2004;
51(1):35-44.
7.
Bonow RO., et al. ACC/AHA Guidelines for the
Management of PatientsWithValvular Heart Disease: A
Report of the American College of Cardiology/American
Heart AssociationTask Force on Practice Guidelines
(Committee to Revise the 1998 Guidelines for the
Management of Patients withValvular Heart Disease).
J.AmCollCardiol. 2006; 48:e1-148.
8.
Aagaard J., et al. Mitral valve replacement with total
preservation of native valves and subvalvular
apparatus. J.HeartValveDis. May 1997; 6(3):274-8;
discussion 279-80.
Table 1: Observed Adverse Event Rates for MVR and DVR (Model 6900)
All patients analyzed: N = 363
Cumulative follow-up: 1100 patient-years
Notes:
1. Late event rates were calculated as linearized rates (%/pt-yr) based on 1072.5 late patient-years
(> 30 days postoperatively).
2. FreedomfromeventrateswerecalculatedusingtheKaplan-Meiermethod.Greenwood’sformulawasusedforcalculation
ofthestandarderrorsoftheseestimates.
3. n = number of events.
Complication
Early Events
Late Events1
Freedom from Event (%) [95% CI]2
n3
%
n
%/pt.-yr.
1 year (n = 287)
5 years (n = 141)
8 years (n = 18)
Mortality (all)
34
9.4
50
4.7
85.5 [81.8, 89.2]
75.4 [70.3, 80.6]
65.4 [57.6, 73.2]
Valve-relatedevents
Mortality(valve-related)
0
0
16
1.5
97.7 [96.0, 99.4]
95.3 [92.8, 97.8]
91.9 [87.5, 96.4]
Explants
0
0
8
0.7
98.7 [98.0, 99.3]
96.7 [95.3, 98.0]
95.6 [93.9, 97.3]
Reoperations
2
0.6
12
1.1
97.1 [96.2, 98.1]
95.1 [93.6, 96.6]
93.0 [90.9, 95.1]
Anticoagulant-related
hemorrhage
2
0.6
9
0.8
97.1 [95.2, 99.0]
97.1 [95.2, 99.0]
94.1 [88.2, 100]
Endocarditis
1
0.3
3
0.3
99.0 [97.9, 100]
98.7 [97.4, 98.9]
98.7 [97.4, 98.9]
Hemolysis
0
0.0
1
0.1
99.7 [99.0, 100]
99.7 [99.0, 100]
99.7 [99.0, 100]
Nonstructural
dysfunction
0
0.0
3
0.3
100 [100, 100]
99.3 [98.0, 100]
98.3 [95.9, 100]
Perivalvular leak (all)
1
0.3
5
0.5
98.4 [97.0, 99.8]
98.4 [97.0, 99.8]
97.3 [94.9, 99.8]
Structural valve
deterioration
0
0.0
5
0.5
100.0 [100, 100]
97.6 [95.2, 100]
92.8 [85.3, 100]
Thromboembolism
5
1.4
8
0.7
97.5 [95.8, 99.2]
96.1 [93.8, 98.5]
96.1 [93.8, 98.5]
Thrombosis
0
0.0
0
0.0
100.0 [100, 100]
100.0 [100, 100]
100.0 [100, 100]
Table 2: Observed Adverse Event Rates (Model 6900P)
All patients analyzed: N = 209
Cumulative follow-up: 873.18 total pt-yrs.
Notes:
1. Late event rates were calculated as linearized rates (%/pt-yr) based on 856.24 late patient-years
(> 30 days postoperatively).
2. FreedomfromeventrateswerecalculatedusingtheKaplan-Meiermethod.Greenwood’sformulawasusedforcalculation
ofthestandarderrorsoftheseestimates.
3. n = number of events.
Complication
Early Events
Late Events1
Freedom from Event (%) [95% CI]2
n3
%
n
%/pt-yr
1 year
5 years
Mortality (all)
3
1.4
45
5.3
93.2 [88.8, 95.9]
74.4 [66.9, 80.5]
Valve-relatedevents
Mortality(valve-related)
1
0.5
12
1.4
98.5 [95.5, 99.5]
92.0 [86.2, 95.5]
Explants
1
0.5
8
0.9
97.5 [94.0, 98.9]
96.5 [92.2, 98.5]
Reoperations
0
0.0
0
0.0
100.0 [100, 100]
100.0 [100, 100]
Bleeding Events
5
2.4
13
1.5
96.1 [92.3, 98.0]
91.9 [86.5, 95.2]
Endocarditis
1
0.5
3
0.4
99.5 [96.6, 99.9]
97.1 [92.1, 98.9]
Nonstructural
dysfunction
0
0.0
1
0.1
99.5 [96.4, 99.9]
99.5 [96.4, 99.9]
Perivalvular leak (all)
1
0.5
2
0.2
99.5 [96.7, 99.9]
98.4 [95.2, 99.5]
Structural valve
deterioration
0
0.0
2
0.2
100.0 [100, 100]
99.0 [93.2, 99.9]
Thromboembolism
4
1.9
12
1.4
97.0 [93.5, 98.7]
91.3 [85.8, 94.7]
Thrombosis
0
0.0
0
0.0
100.0 [100, 100]
100.0 [100, 100]
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%
Table 3: Preoperative Patient Demographics (Model 6900)
Note:
1. n = number of patients in each category; N = total number of study patients.
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%
Table 4: Preoperative Patient Demographics (Model 6900P)
Note:
1. n = number of patients in each category; N = total number of study patients.
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
Table 5: Operative Patient Demographics (Model 6900)
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 = CerebralVascular Accident
Table 6: 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%
AorticValve/Annulus Repair
3
1.4%
CABG3
58
27.8%
Permanent Pacemaker
1
0.5%
TricuspidValve/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%
PeripheralVascular 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%
NYHA Functional Class
Preoperative
Assessment
Postoperative Assessments
1 to 2Year
5Year
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 7: Effectiveness Outcomes, Functional NYHA (Model 6900)
NYHA Functional Class
Preoperative
Assessment
Postoperative Assessments
1Year
5Year
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.
Table 8: Effectiveness Outcomes, Functional NYHA (Model 6900P)
Hemodynamic
Parameter
Results ByValve Size
25 mm
27 mm
29 mm
31 mm
33 mm
Discharge/Early Post-Implant (n = 130, 109 MVR2 and 21 DVR3)
Mean gradient4
n = 3
n = 23
n = 36
n = 23
n = 3
• mean ± sd
5.7 ± 1.2
4.2 ± 1.7
4.2 ± 1.7
3.6 ± 1.0
7.5 ± 5.8
• min, max
5, 7
2, 9
1, 8
2, 5
3, 14
EOA5
n = 1
n = 17
n = 22
n = 25
n = 5
• mean ± sd
1.5
2.9 ± 0.9
3.1 ± 0.9
2.5 ± 0.7
3.0 ± 1.2
• min, max
1.5, 1.5
1.3, 4.1
1.4, 4.2
1.5, 3.8
1.6, 4.9
Regurgitation6
n = 3
n = 28
n = 51
n = 40
n = 8
0
3/3 (100%)
22/28 (79%)
36/51 (71%)
30/40 (75%)
4/8 (50%)
1+
0/3 (0%)
5/28 (18%)
13/51 (25%)
7/40 (18%)
4/8 (50%)
2+
0/3 (0%)
0/28 (0%)
1/51 (2%)
3/40 (7%)
0/8 (0%)
3+
0/3 (0%)
0/28 (0%)
1/51 (2%)
0/40 (0%)
0/8 (0%)
4+
0/3 (0%)
0/28 (0%)
0/51 (0%)
0/40 (0%)
0/8 (0%)
Not available
0/3 (0%)
1/28 (3%)
0/51 (0%)
0/40 (0%)
0/8 (0%)
3 to 6 Month Post-Implant Interval (n = 49, 42 MVR2 and 7 DVR3)
Mean gradient4
n = 5
n = 19
n = 15
n = 5
n = 2
• mean ± sd
6.4 ± 1.7
5.3 ± 5
3.4 ± 1.2
4 ± 1.9
4 ± 0
• min, max
5, 9
2, 25
2, 6
2, 7
4, 4
EOA5
n = 5
n = 18
n = 13
n = 5
n = 2
• mean ± sd
2.9 ± 0.8
2.6 ± 0.7
2.8 ± 0.6
2.9 ± 0.3
2.6 ± 1
• min, max
1.8, 3.6
1.5, 5
2, 3.8
2.4, 3.3
2, 3.3
Regurgitation6
n = 5
n = 21
n = 15
n = 6
n = 2
0
3/5 (60%)
17/21 (81%)
6/15 (40%)
4/6 (67%)
1/2 (50%)
1+
0/5 (0%)
4/21 (19%)
8/15 (53%)
2/6 (33%)
0/2 (0%)
2+
1/5 (20%)
0/21 (0%)
1/15 (7%)
0/6 (0%)
1/2 (50%)
3+
0/5 (0%)
0/21 (0%)
0/15 (0%)
0/6 (0%)
0/2 (0%)
4+
1/5 (20%)
0/21 (0%)
0/15 (0%)
0/6 (0%)
0/2 (0%)
Not available
0/5 (0%)
0/21 (0%)
0/15 (0%)
0/6 (0%)
0/2 (0%)
1 to 2Year Post-Implant Interval (n = 131, 114 MVR2 and 17 DVR3)
Mean gradient4
n = 3
n = 40
n = 47
n = 27
n = 4
• mean ± sd
5.2 ± 0.7
4.1 ± 1.6
3.5 ± 1.8
3.1 ± 1.4
2.1 ± 0.5
• min, max
4.7, 6
1, 7
1, 10
1, 7
1.5, 2.7
EOA5
n = 2
n = 35
n = 46
n = 29
n = 5
• mean ± sd
1.8 ± 0.4
2.3 ± 0.6
2.6 ± 0.5
2.6 ± 0.7
2.5 ± 0.5
• min, max
1.5, 2.0
1.2, 3.5
1.1, 3.7
1.1, 3.7
2.1, 3.2
Regurgitation6
n = 4
n = 42
n = 51
n = 29
n = 5
0
2/4 (50%)
31/42 (74%)
36/51 (71%)
17/29 (59%)
3/5 (60%)
1+
1/4 (25%)
9/42 (21%)
11/51 (21%)
8/29 (27%)
1/5 (20%)
2+
1/4 (25%)
2/42 (5%)
4/51 (8%)
2/29 (7%)
1/5 (20%)
3+
0/4 (0%)
0/42 (0%)
0/51 (0%)
2/29 (7%)
0/5 (0%)
4+
0/4 (0%)
0/42 (0%)
0/51 (0%)
0/29 (0%)
0/5 (0%)
Not available
0/4 (0%)
0/42 (0%)
0/51 (0%)
0/29 (0%)
0/5 (0%)
Table 9: Effective Outcomes, Hemodynamic Results1 (Model 6900)
Table 9: Effective Outcomes, Hemodynamic Results1 (Model 6900), Continued
Hemodynamic
Parameter
Results ByValve Size
25 mm
27 mm
29 mm
31 mm
33 mm
5Year Post-Implant Interval (n = 11, 9 MVR2 and 2 DVR3)
Mean gradient4
n = 0
n = 6
n = 5
n = 0
n = 0
• mean ± sd
N/A
8.8 ± 8.1
5.1 ± 2.3
N/A
N/A
• min, max
N/A
4, 25
3, 8
N/A
N/A
EOA5
n = 0
n = 2
n = 4
n = 0
n = 0
• mean ± sd
N/A
2.0 ± 1.5
2.9 ± 0.6
N/A
N/A
• min, max
N/A
1.0, 3.1
2.1, 3.5
N/A
N/A
Regurgitation6
n = 0
n = 6
n = 5
n = 0
n = 0
0
0/0 (0%)
4/6 (66%)
2/5 (40%)
0/0 (0%)
0/0 (0%)
1+
0/0 (0%)
1/6 (17%)
3/5 (60%)
0/0 (0%)
0/0 (0%)
2+
0/0 (0%)
1/6 (17%)
0/5 (0%)
0/0 (0%)
0/0 (0%)
3+
0/0 (0%)
0/6 (0%)
0/5 (0%)
0/0 (0%)
0/0 (0%)
4+
0/0 (0%)
0/6 (0%)
0/5 (0%)
0/0 (0%)
0/0 (0%)
Not available
0/0 (0%)
0/6 (0%)
0/5 (0%)
0/0 (0%)
0/0 (0%)
Notes:
1. Hemodynamic evaluations were performed using transthoracic echocardiography (TTE) and in some cases,
transesophageal echocardiography (TEE).
2. MVR = mitral valve replacement
3. DVR = double valve replacement
4. Mean gradient in mmHg
5. EOA: Effective Orifice Area, cm2
6. Regurgitation = none, 0; mild, 1+; moderate, 2+; moderate/severe, 3+; severe, 4+
Continued on next column.
Hemodynamic
Parameter
Results ByValve Size
25 mm
27 mm
29 mm
31 mm
33 mm
Discharge/Early Post-Implant
Mean gradient2
n = 24
n = 35
n = 83
n = 42
n = 16
• mean ± sd
6.4 ± 1.87
4.4 ± 1.52
3.4 ± 1.47
3.3 ± 1.20
4.0 ± 1.38
• min, max
3, 10
1.96, 8
1.4, 9
1, 7
1.5, 6.91
EOA3
n = 8
n = 27
n = 77
n = 41
n = 16
• mean ± sd
2.7 ± 0.87
2.8 ± 0.58
2.9 ± 0.93
2.5 ± 0.67
2.4 ± 0.52
• min, max
1.46, 4.4
1.5, 3.9
1.58, 6
1.32, 4.2
1.55, 3.31
Regurgitation4
n = 27
n = 37
n = 83
n = 43
n = 17
Trivial / None
19/27 (70%)
29/37 (78%)
76/83 (92%)
39/43 (91%)
15/17 (88%)
1+ Mild
6/27 (22%)
7/37 (19%)
7/83 (8%)
4/43 (9%)
1/17 (6%)
2+ Moderate
1/27 (4%)
1/37 (3%)
0/83 (0%)
0/43 (0%)
0/17 (0%)
3+Moderate/Severe
0/27 (0%)
0/37 (0%)
0/83 (0%)
0/43 (0%)
1/17 (6%)
4+ Severe
0/27 (0%)
0/37 (0%)
0/83 (0%)
0/43 (0%)
0/17 (0%)
Not available
1/27 (4%)
0/37 (0%)
0/83 (0%)
0/43 (0%)
0/17 (0%)
3 to 6 Month Post-Implant Interval
Mean gradient2
n = 0
n = 4
n = 3
n = 2
n = 0
• mean ± sd
0 ± 0
4.4 ± 2.25
2.3 ± 0.89
6.6 ± 2.05
0 ± 0
• min, max
0, 0
2.5, 7.5
1.3, 3
5.1, 8
0, 0
EOA3
n = 0
n = 3
n = 3
n = 1
n = 1
• mean ± sd
0 ± 0
2.4 ± 0.74
3.2 ± 0.88
2.5 ± 0.00
1.2 ± 0.00
• min, max
0, 0
1.6, 3
2.3, 4.05
2.47, 2.47
1.22, 1.22
Regurgitation4
n = 0
n = 5
n = 3
n = 2
n = 2
Trivial / None
0
3/5 (60%)
2/3 (67%)
2/2 (100%)
2/2 (100%)
1+ Mild
0
1/5 (20%)
1/3 (33%)
0/2 (0%)
0/2 (0%)
2+ Moderate
0
1/5 (20%)
0/3 (0%)
0/2 (0%)
0/2 (0%)
3+Moderate/Severe
0
0/5 (0%)
0/3 (0%)
0/2 (0%)
0/2 (0%)
4+ Severe
0
0/5 (0%)
0/3 (0%)
0/2 (0%)
0/2 (0%)
Not available
0
0/5 (0%)
0/3 (0%)
0/2 (0%)
0/2 (0%)
1Year Post-Implant Interval
Mean gradient2
n = 16
n = 27
n = 63
n = 34
n = 15
• mean ± sd
5.9 ± 2.36
4.0 ± 1.45
3.0 ± 1.61
3.3 ± 1.26
3.4 ± 1.25
• min, max
3, 12
2, 7
1, 12
1.5, 7
1.9, 6.3
EOA3
n = 3
n = 21
n = 59
n = 32
n = 15
• mean ± sd
2.3 ± 0.16
2.4 ± 0.76
2.6 ± 0.74
2.5 ± 0.67
2.3 ± 0.83
• min, max
2.09, 2.4
1.27, 4.76
1.5, 5.7
1.5, 4
1.2, 3.8
Regurgitation4
n = 20
n = 28
n = 65
n = 34
n = 16
Trivial / None
17/20 (85%)
24/28 (86%)
53/65 (82%)
29/34 (85%)
13/16 (81%)
1+ Mild
3/20 (15%)
3/28 (11%)
6/65 (9%)
3/34 (9%)
3/16 (19%)
2+ Moderate
0/20 (0%)
0/28 (0%)
3/65 (5%)
2/34 (6%)
0/16 (0%)
3+Moderate/Severe
0/20 (0%)
0/28 (0%)
1/65 (2%)
0/34 (0%)
0/16 (0%)
4+ Severe
0/20 (0%)
0/28 (0%)
0/65 (0%)
0/34 (0%)
0/16 (0%)
Not available
0/20 (0%)
1/28 (4%)
2/65 (3%)
0/34 (0%)
0/16 (0%)
Table 10: Effectiveness Outcomes, Hemodynamic Results (Model 6900P)1
Notes:
1. Hemodynamic evaluations were performed using transthoracic echocardiography (TTE) and in some cases,
transesophageal echocardiography (TEE).
2. Mean gradient in mmHg
3. EOA: Effective Orifice Area, cm2
4. Regurgitation =Trivial/none, 0; mild, 1+; moderate, 2+; moderate/severe, 3+; severe, 4+

Magna Mitral Post Approval Study Protocol 2006-05   
 
 REV I  November 18, 2013  
 
 
 
 
 
 This document and the information contained herein is considered Proprietary and Confidential  
and may not be reproduced, used or disclosed without written permission from Edwards Lifesciences LLC. 
 
 
- pg 74 of 80 - 
16.0  APPENDIX 5: CASE REPORT FORMS 

 
 
Study Number 2006-05 
Carpentier-Edwards PERIMOUNT Magna Mitral Valve 
Patient Selection Data 
FORM 1 
 
Page 1 of 1 
 
Patient Study ID # 2 0 0 6 0 5 
 
 
 
       
        Clinic # 
 
 
 
 
 
 
 
White and Yellow:  Return to Edwards Lifesciences, Clinical Affairs    Pink:  Retain for your Records 
PROPRIETARY DATA:  THIS DOCUMENT AND INFORMATION CONTAINED HEREIN MAY NOT BE REPRODUCED, USED, OR DISCLOSED WITHOUT WRITTEN PERMISSION OF EDWARDS LIFESCIENCES,  
 
HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
PREOPERATIVE DATA  REV E 20110526 
FOR 
EDWARDS 
USE ONLY 
Clinical Review: 
Data Management: 
 
First Review: 
Second Review: (optional) 
First Data Entry: 
Second Data Entry: 
Subevent # 
(optional) 
By:   
By: 
By: 
By: 
Date:__ __ __/__ __/__ __ __ __ Date: __ __ __/__ __/__ __ __ __ Date: __ __ __/__ __/__ __ __ __ Date: __ __ __/__ __/__ __ __ __ 
 
I. 
INCLUSION CRITERIA  A NO answer excludes the subject. 
 
YES 
NO 
1. 
 
 
The patient requires, as indicated in the preoperative evaluation, a mitral valve replacement. 
2. 
 
 
The patient has signed and dated the patient informed consent form prior to surgery. 
3. 
 
 
The patient is expected to survive the surgery and be discharged. 
4. 
 
 
The patient is geographically stable and agrees to attend follow-up assessments. 
5. 
 
 
The patient is > or = 18 years of age. 
 
II. 
EXCLUSION CRITERIA   A YES answer excludes the subject. 
 
YES 
NO 
1. 
 
 
The patient has any known non-cardiac life-threatening disease which will limit the patient’s life  
  
  
expectancy below 1 year. 
2. 
 
 
The patient has active endocarditis within the last 3 months. 
3. 
 
 
The patient is pregnant or lactating. 
4. 
 
 
The patient is an intravenous drug abuser. 
5. 
 
 
The patient is currently a prison inmate. 
6. 
 
 
The patient is currently participating in the study of an investigational drug or device. 
7. 
 
 
The patient requires replacement of a native or prosthetic tricuspid or pulmonic valve. 
8. 
 
 
The patient was previously enrolled in the study. 
9. 
 
 
The patient has had prior aortic, tricuspid and/or pulmonary valve surgery, which included implantation of 
  
 
a bioprosthetic valve, mechanical valve and/or annuloplasty device that will remain in situ. 
10. 
 
 
The patient requires replacement of a native or prosthetic aortic valve with a prosthesis other than a  
  
 
 commercially available Carpentier-Edwards PERIMOUNT Valve (ie, models 2700, 2700TFX, 2800,  
 
 
 
2800TFX, 2900, 3000, 3000TFX, 3300TFX). 
III. 
STUDY INFORMED CONSENT 
 
     Yes    No 
1. 
 
 Signed Informed Consent  
 
 
 
 
Date informed consent signed:  
 
 
 
 
 
  
 
 
  
 
:  
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
 
Time (24 hour format) 
 
I HAVE  R E VIE WE D AND AGR E E  WITH ALL DATA E NTE R E D ON THIS  FOR M 
                                                                                                                                                                                DATE SIGNED 
  
 
  
 
 
 
 
 
 
 
 
INVESTIGATOR SIGNATURE 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 

 
 
STUDY NUMBER 2006-05 
CARPENTIER-EDWARDS PERIMOUNT MAGNA MITRAL EASE 
P R E OPE R ATIVE  DATA 
FOR M 2.0 
PAGE  1 OF 5 
 
Patient Study ID # 2 0 0 6 0 5 
 
 
 
 
 
Clinic # 
 
 
  
 
 
 
White and Yellow:  Return to Edwards Lifesciences, Clinical Affairs    Pink:  Retain for your Records 
PROPRIETARY DATA:  THIS DOCUMENT AND INFORMATION CONTAINED HEREIN MAY NOT BE REPRODUCED, USED, OR DISCLOSED WITHOUT WRITTEN PERMISSION OF EDWARDS LIFESCIENCES  
 
HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
PREOPERATIVE DATA REV E 20110526 
FOR 
EDWARDS 
USE ONLY 
CLINICAL REVIEW: 
DATA MANAGEMENT: 
 
FIRST REVIEW: 
SECOND REVIEW: (OPTIONAL) 
FIRST DATA ENTRY: 
SECOND DATA ENTRY: 
SUBEVENT #  
(OPTIONAL) 
BY:   
BY: 
BY: 
BY: 
DATE: __ __ __/__ __/__ __ __ __ 
DATE:__ __ __/__ __/__ __ __ __ 
DATE: __ __ __/__ __/__ __ __ __ 
DATE: __ __ __/__ __/__ __ __ __ 
 
 
1. DATE OF BIRTH:     
 
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
2. SEX:  
 
Male     
 Female 
3.   PHYSICAL ASSESSMENT: 
HEART RATE 
 
 
 
(bpm) 
 
 
 
 
 
 
 
 
 
 
 
 
HEIGHT 
 
 
 
(cm) 
 
 
 
 
 
 
 
 
 
 
 
 
WEIGHT 
 
 
 
(kg) 
 
 
 
 
 
 
 
 
 
 
 
 
BLOOD PRESSURE 
 
 
 
 
 
 
 
mmHg 
 
 
 
 
 
 
 
4. PREOPERATIVE NYHA FUNCTIONAL CLASS: 
 
 Class I    
 Class II       
 Class III        
 Class IV 
 NAV 
5. NON-CARDIOVASCULAR CONDITIONS:  (Past or present, check all that apply) 
Yes No   
 
 
 
 
  Smoking (Current) 
 
 
 
 
  Smoking (Past) 
 
 
 
 
  Drug Abuse 
 
 
 
 
  Alcohol Abuse 
 
 
 
 
  Rheumatic Fever 
 
 
 
 
  Cancer, specify:  _________ 
 
 
 
 
  Liver Disease 
 
 
 
 
  Renal Failure   if yes,       
  Dialysis    
  No Dialysis 
 
 
 
  Pulmonary Disease 
 
 
 
 
  Renal Dysfunction 
 
 
 
 
  Diabetes    if yes,  
 Insulin dependent   
 Non insulin dependent    
 
 
  Immunosuppressive Therapy 
 
 
 
 
 
  Calcium Metabolic Disorder 
 
 
 
 
 
  Respiratory Dysfunction and/or COPD 
 
 
 
 
 
  Respiratory Failure (Requires ventilator support) (if yes-exclude) 
 
 
 
  Peripheral Vascular Disease 
 
 
 
  TIA /CVA / RIND /COMA 
 
 
 
  Other CNS disorder 
 
 
 
  Other, specify:  ___________________ 
 
 

 
 
STUDY NUMBER 2006-05 
CARPENTIER-EDWARDS PERIMOUNT MAGNA MITRAL EASE 
P R E OPE R ATIVE  DATA 
FOR M 2.0 
PAGE  2 OF 5 
 
Patient Study ID # 2 0 0 6 0 5 
 
 
 
 
 
Clinic # 
 
 
  
 
 
 
White and Yellow:  Return to Edwards Lifesciences, Clinical Affairs    Pink:  Retain for your Records 
PROPRIETARY DATA:  THIS DOCUMENT AND INFORMATION CONTAINED HEREIN MAY NOT BE REPRODUCED, USED, OR DISCLOSED WITHOUT WRITTEN PERMISSION OF EDWARDS LIFESCIENCES  
 
HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
PREOPERATIVE DATA REV E 20110526 
FOR 
EDWARDS 
USE ONLY 
CLINICAL REVIEW: 
DATA MANAGEMENT: 
 
FIRST REVIEW: 
SECOND REVIEW: (OPTIONAL) 
FIRST DATA ENTRY: 
SECOND DATA ENTRY: 
SUBEVENT #  
(OPTIONAL) 
BY:   
BY: 
BY: 
BY: 
DATE: __ __ __/__ __/__ __ __ __ 
DATE:__ __ __/__ __/__ __ __ __ 
DATE: __ __ __/__ __/__ __ __ __ 
DATE: __ __ __/__ __/__ __ __ __ 
 
 
6. CARDIOVASCULAR MEDICAL HISTORY / RISK FACTORS: (As noted by physician) 
Yes No 
  
 
 
 
 
   Dyslipidemia / Hypercholesterolemia 
 
 
 
 
 
Marfan’s Syndrome (if yes, exclude) 
 
 
 
 
Rheumatic Fever 
 
 
 
 
Carotid Artery Disease 
 
 
 
 
Coronary Artery Disease 
 
 
 
 
Atrial Enlargement 
 
 
 
 
Cardiomyopathy 
 
 
 
 
Coagulopathy, specify: _____________________ 
 
 
 
 
Myocardial Infarction 
 
 
 
 
Arrhythmias 
  Not Treated 
 
  Medically Treated 
 
 
 
 
 
   Implantation of AICD / Pacemaker 
 
 
 
 
Congestive Heart Failure 
 
 
 
 
Endocarditis 
  Active (within last 3 months) (exclusion criteria) 
 Not Active 
 
 
 
Pulmonary Hypertension 
 
 
 
 
Systemic Hypertension 
 
 
 
 
Tricuspid Insufficiency, Severity* :___________________ 
 
 
 
 
Aortic Insufficiency, Severity* :___________________ 
 
 
 
 
Aortic stenosis, Severity* :___________________ 
 
 
 
 
(*Severity:  +1 Trivial/Trace, +2 Mild, +3 Moderate, +4 Severe) 
 
 
 
 
Angina 
  Stable 
 
  Unstable 
 
 
 
 
Aortic Aneurysm 
 
 
 
 
Cardiomegaly 
 
 
 
 
Hypotension 
 
 
 
 
Pulmonary embolism 
 
 
 
 
Ventricular aneurysm 
 
 
 
 
Other, specify: ____________________ 
 
 
 
 
 
 
 
 
 

 
 
STUDY NUMBER 2006-05 
CARPENTIER-EDWARDS PERIMOUNT MAGNA MITRAL EASE 
P R E OPE R ATIVE  DATA 
FOR M 2.0 
PAGE  3 OF 5 
 
Patient Study ID # 2 0 0 6 0 5 
 
 
 
 
 
Clinic # 
 
 
  
 
 
 
White and Yellow:  Return to Edwards Lifesciences, Clinical Affairs    Pink:  Retain for your Records 
PROPRIETARY DATA:  THIS DOCUMENT AND INFORMATION CONTAINED HEREIN MAY NOT BE REPRODUCED, USED, OR DISCLOSED WITHOUT WRITTEN PERMISSION OF EDWARDS LIFESCIENCES  
 
HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
PREOPERATIVE DATA REV E 20110526 
FOR 
EDWARDS 
USE ONLY 
CLINICAL REVIEW: 
DATA MANAGEMENT: 
 
FIRST REVIEW: 
SECOND REVIEW: (OPTIONAL) 
FIRST DATA ENTRY: 
SECOND DATA ENTRY: 
SUBEVENT #  
(OPTIONAL) 
BY:   
BY: 
BY: 
BY: 
DATE: __ __ __/__ __/__ __ __ __ 
DATE:__ __ __/__ __/__ __ __ __ 
DATE: __ __ __/__ __/__ __ __ __ 
DATE: __ __ __/__ __/__ __ __ __ 
 
 
7. PREOPERATIVE CARDIAC RHYTHM (Check all that apply)  ECG 
  Not Done (Complete Protocol Deviation) 
  Done     
Date: 
 
 
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
 
 
 
 
 
Normal Sinus 
  Atrial Fibrillation 
 
  Atrial Flutter 
  Paced 
 
AV Block    (Indicate degree) 
 
 1st
  2
  
nd
 3
  
rd
 
   
 
Bundle Branch Block (Indicate branch) 
 
 Left 
 Right 
 
 
Other, specify: _________________ 
 
 
 
8.  PREVIOUS PROCEDURES / MEDICATIONS 
8a. Preoperative Valve Repair(s): 
      Yes  No 
 
 
 Aortic 
 
 
 Mitral 
 
 
 Pulmonic 
 
 
 Tricuspid 
 
 
 Unknown  
8b. Preoperative Valve Replacement(s): 
      Yes  No 
 
 
 Aortic 
 
 
 Mitral 
 
 
 Pulmonic 
 
 
 Tricuspid 
 
 
 Unknown  
NOTE:  If a bioprosthesis or mechanical valve was previously implanted in the aortic, tricuspid and/or pulmonary 
position, which remains in situ, patient is EXCLUDED. 
 
8c. Other Preoperative Cardiovascular Surgery: 
      Yes  No 
 
 
 PTCA 
 
 
 Endarterectomy 
    
 CABG, Number of CABG: ________   
Date: 
 
 
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
   
 Tricuspid 
   
  Carotid Surgery   
Date: 
 
 
 
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
   
  AICD Implant 
   
  Pacemaker Implant 

 
 
STUDY NUMBER 2006-05 
CARPENTIER-EDWARDS PERIMOUNT MAGNA MITRAL EASE 
P R E OPE R ATIVE  DATA 
FOR M 2.0 
PAGE  4 OF 5 
 
Patient Study ID # 2 0 0 6 0 5 
 
 
 
 
 
Clinic # 
 
 
  
 
 
 
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HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
PREOPERATIVE DATA REV E 20110526 
FOR 
EDWARDS 
USE ONLY 
CLINICAL REVIEW: 
DATA MANAGEMENT: 
 
FIRST REVIEW: 
SECOND REVIEW: (OPTIONAL) 
FIRST DATA ENTRY: 
SECOND DATA ENTRY: 
SUBEVENT #  
(OPTIONAL) 
BY:   
BY: 
BY: 
BY: 
DATE: __ __ __/__ __/__ __ __ __ 
DATE:__ __ __/__ __/__ __ __ __ 
DATE: __ __ __/__ __/__ __ __ __ 
DATE: __ __ __/__ __/__ __ __ __ 
 
 
   
  Unknown 
   
   Other, specify: ____________________________ 
8d. Preoperative Antithromboembolic Therapy: (Check all that apply) 
 
 
 
  None 
 
  Anticoagulants (Heparin, Coumarine Derivates) 
 
   Antiplatelets (Clopidogrel, Dipyridamole, Ticlopidine, Prasugrel) 
               
  Aspirin (Acetylsalicylic Acid) 
 
  Other, Specify:_____________________ 
 
9.  ECHOCARDIOGRAPHY: (Within 6 months prior
 
 No, not performed (Complete Protocol Deviation) 
 to implant date) 
       
 Yes, performed (Complete Echo Tracking Form and send form to Core Lab with Media) 
 
10. BLOOD DATA (Drawn within 30 days prior to implant date) 
  Not Done (complete Protocol Deviation) 
  Done       Date: 
 
 
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
 
PREOPERATIVE COAGULATION PROFILE:   
 
NAP (No coumarine derivative treatment) 
 
Int’l Normalized Ratio (INR) 
OR 
 
Partial Thromboplastin Time (PTT) 
 
 
 
• 
 
 
 
 
 
 
 
 
 
 
• 
(sec)  
 
 
  
ALWAYS COMPLETE A 
A. 
BLOOD PARAMETER 
VALUE 
UNITS 
WITHIN NORMAL 
RANGE? 
IF NO, CLINICALLY 
SIGNIFICANT? 
YES 
NO 
YES 
NO 
WHITE BLOOD CELLS 
 
(x 103
 
/µL) 
 
 
 
RED BLOOD CELLS 
 
(x 106
 
/µL) 
 
 
 
HEMOGLOBIN 
 
(gm/dL) 
 
 
 
 
HEMATOCRIT 
 
(%) 
 
 
 
 
RETICULOCYTES 
 
(%) 
 
 
 
 
PLATELET COUNT 
 
(x 103
 
/µL) 
 
 
 
 
 
 
 

 
 
STUDY NUMBER 2006-05 
CARPENTIER-EDWARDS PERIMOUNT MAGNA MITRAL EASE 
P R E OPE R ATIVE  DATA 
FOR M 2.0 
PAGE  5 OF 5 
 
Patient Study ID # 2 0 0 6 0 5 
 
 
 
 
 
Clinic # 
 
 
  
 
 
 
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HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
PREOPERATIVE DATA REV E 20110526 
FOR 
EDWARDS 
USE ONLY 
CLINICAL REVIEW: 
DATA MANAGEMENT: 
 
FIRST REVIEW: 
SECOND REVIEW: (OPTIONAL) 
FIRST DATA ENTRY: 
SECOND DATA ENTRY: 
SUBEVENT #  
(OPTIONAL) 
BY:   
BY: 
BY: 
BY: 
DATE: __ __ __/__ __/__ __ __ __ 
DATE:__ __ __/__ __/__ __ __ __ 
DATE: __ __ __/__ __/__ __ __ __ 
DATE: __ __ __/__ __/__ __ __ __ 
 
 
COMPLETE EITHER B OR C 
B.  
BLOOD PARAMETER 
VALUE 
UNITS 
WITHIN NORMAL 
RANGE? 
IF NO, CLINICALLY 
SIGNIFICANT? 
YES 
NO 
YES 
NO 
PLASMA FREE 
HEMOGLOBIN 
 
(mg/dL) 
 
 
 
 
 
OR 
 
C.  
BLOOD PARAMETER 
VALUE 
UNITS 
WITHIN NORMAL 
RANGE? 
IF NO, CLINICALLY 
SIGNIFICANT? 
YES 
NO 
YES 
NO 
HAPTOGLOBIN 
 
(mg/dL) 
 
 
 
 
SERUM LDH 
 
(U/L) 
 
 
 
 
 
ELEVATED SERUM LDH – FRACTIONED 
 
LDH  1 
LDH  2 
LDH  3 
LDH  4 
LDH  5 
(%) 
(%) 
(%) 
(%) 
(%) 
 
 
PREGNANCY TEST     
  NAP – (subject is male, or female who is post-menopausal / surgically sterile) 
 
  Not Done (complete Protocol Deviation) 
  Done       Date: 
 
 
 
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
Check one:  
 Urine Test    
 Blood Test  
Results  
  Positive (Complete Protocol Deviation Data) 
  Negative 
11.  QUALITY OF LIFE SURVEY (EQ-5D): (Within 3 months prior
 
 No, patient did not complete (Complete Protocol Deviation Data) 
 to implant date) 
 
 Yes, patient completed (Complete QOL Survey Data) 
Comments: ___________________________________________________________________________________ 
_____________________________________________________________________________________________ 
I HAVE  R E VIE WE D AND AGR E E  WITH ALL DATA E NTE R E D ON THIS  FOR M 
 
  
 
DATE SIGNED  
 
 
 
 
 
 
 
 
INVESTIGATOR SIGNATURE 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 

 
 
 
 
 
Study Number 2006-05 
Carpentier-Edwards PERIMOUNT Magna Mitral Valve 
Operative Data 
FORM 3 
 
PAGE  1 OF 5 
 
Patient Study ID # 2 0 0 6 0 5 
 
 
 
       
        Clinic # 
 
 
 
 
 
 
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HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
OPERATIVE DAT, REV  E 20110526 
FOR 
EDWARDS 
USE ONLY 
Clinical Review: 
Data Management: 
 
First Review: 
Second Review: (optional) 
First Data Entry: 
Second Data Entry: 
Subevent #  
(optional) 
By:   
By: 
By: 
By: 
Date: __ __ __/__ __/__ __ __ __ 
Date:__ __ __/__ __/__ __ __ __ 
Date: __ __ __/__ __/__ __ __ __ 
Date: __ __ __/__ __/__ __ __ __ 
 
 
1. 
IMPLANT DATE:  
 
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
2. 
IMPLANTING SURGEON:  __________________________________________ 
3.       ETIOLOGY (Answer each Yes or No): 
YES    NO 
    
 Rheumatic 
    
 Degenerative 
    
 Congenital 
    
 Remote Endocarditis 
    
 Ischemic 
    
 Mitral Valve Prolapse 
    
 Failed Repair 
    
 Calcified 
 
 
 Mild 
 Moderate  
 Severe   
 Other, specify: ______________________ 
 
 
 
4.    DIAGNOSIS FOR CURRENT REPLACEMENT (check one): 
  Stenosis 
  Regurgitation 
  Mixed Disease (Stenosis and Regurgitation) 
  Prosthetic Valve Dysfunction 
  Other, specify: ______________________ 
 
5.    PRE-IMPLANT CONDITION Answer each Yes or No: 
5a. Anterior of Annulus: 
           YES  NO  
  
  
 Normal 
 
  
 Calcified 
 
  
 Dilated 
5b. Posterior of Annulus: 
           YES  NO  
  
   
 Normal 
 
   
 Calcified 
 
   
 Dilated 
 

 
 
 
 
 
Study Number 2006-05 
Carpentier-Edwards PERIMOUNT Magna Mitral Valve 
Operative Data 
FORM 3 
 
PAGE  2 OF 5 
 
Patient Study ID # 2 0 0 6 0 5 
 
 
 
       
        Clinic # 
 
 
 
 
 
 
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HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
OPERATIVE DAT, REV  E 20110526 
FOR 
EDWARDS 
USE ONLY 
Clinical Review: 
Data Management: 
 
First Review: 
Second Review: (optional) 
First Data Entry: 
Second Data Entry: 
Subevent #  
(optional) 
By:   
By: 
By: 
By: 
Date: __ __ __/__ __/__ __ __ __ 
Date:__ __ __/__ __/__ __ __ __ 
Date: __ __ __/__ __/__ __ __ __ 
Date: __ __ __/__ __/__ __ __ __ 
 
 
 
5c. Chordae: 
             YES  NO  
  
   
 Normal 
 
   
 Calcified 
 
   
 Elongation 
 
   
 Tethered 
 
   
 Ruptured 
 
5d.  LVOT: 
 
YES  NO  
  
    
 Normal 
 
    
 Obstructed 
 
5e.  LV Wall: 
 
YES  NO  
  
    
 Normal 
 
    
 Hypertrophic 
 
    
 Friable Tissue 
 
    
 Other, specify: ___________________________ 
 
  6.   PREPARATION  PROCEDURE: 
 
6a.  Debridement Procedure: 
 
 
  None 
 
 
  Full 
 
 
  Partial 
     
6b.   Leaflets and Subvalvular Apparatus 
 
   Preserved  
 
   Partially Removed  (Specify): __________________________________________________ 
 
   Removed 
 7. STUDY VALVE IMPLANTATION: 
  7a  Study Valve Implanted:  
 Yes    
 No, explain:______________________________________________ 
 
7b.  Valve Size: _________________________ mm 
 
7c. Tissue Annulus Diameter: 
 
 
Magna Mitral Sizer (requested):_____________mm 
              Hegar Dilator (optional):  __________________mm 
 
7d.  Valve Model No.  
 
  7000  
  7000TFX 
  7200TFX 
  7300 
   7300TFX 
 7e.  Valve Serial No. ____________________ 

 
 
 
 
 
Study Number 2006-05 
Carpentier-Edwards PERIMOUNT Magna Mitral Valve 
Operative Data 
FORM 3 
 
PAGE  3 OF 5 
 
Patient Study ID # 2 0 0 6 0 5 
 
 
 
       
        Clinic # 
 
 
 
 
 
 
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HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
OPERATIVE DAT, REV  E 20110526 
FOR 
EDWARDS 
USE ONLY 
Clinical Review: 
Data Management: 
 
First Review: 
Second Review: (optional) 
First Data Entry: 
Second Data Entry: 
Subevent #  
(optional) 
By:   
By: 
By: 
By: 
Date: __ __ __/__ __/__ __ __ __ 
Date:__ __ __/__ __/__ __ __ __ 
Date: __ __ __/__ __/__ __ __ __ 
Date: __ __ __/__ __/__ __ __ __ 
 
 
 
  7f.  Valve Position: 
  
 
 
Supra-annular 
 
 
 
Intra-annular 
 
  7g.  Suture Technique: 
 
 
 
Everting Mattress  
 
 
 
Non-Everting Mattress 
              
 
Continuous  
 
 
 
Other, specify:  ____________________ 
 
 
 
     7h. Suture Pattern on Sewing Ring: 
 
 
Anterior:     
 Uniform Suture Bite Depth  
 
 
 
     
 Non-Uniform Suture Bite Depth 
 
 
Posterior:   
 Uniform Suture Bite Depth 
 
 
 
      
 Non-Uniform Suture Bite Depth 
 
 
7i.  Needle Penetration into Annulus: 
 
 
 
 
Easy 
 
 
 
Difficult, because tissue is (check all that apply): 
 
 
 
 
Calcified 
 
 
 
 
Scarred / Fibrous 
 
 
 
 
Friable 
 
 
 
 
Other, specify:   _______________________ 
 
 
 
 
 
7j.  Sewing Cuff Compliance to Annulus: 
 
 
Anterior:    
 Complete 
 
 
 
 
     
 Non-Complete but Satisfactory 
 
 
 
    
 Non-Complete (Explant) 
 
 
Posterior:  
 Complete 
 
 
 
 
 
 Non-Complete but Satisfactory 
 
 
 
 
 Non-Complete (Explant) 
 
 
 
 
 
7k.  Pledgets: 
 
 
 
  Yes 
  No 
 
 
 
 7l.  Difficulty in Seating Valve in Annulus 
 
 
 
No 
 
 
 
Yes (Explain): ___________________________________________________________ 
 
 

 
 
 
 
 
Study Number 2006-05 
Carpentier-Edwards PERIMOUNT Magna Mitral Valve 
Operative Data 
FORM 3 
 
PAGE  4 OF 5 
 
Patient Study ID # 2 0 0 6 0 5 
 
 
 
       
        Clinic # 
 
 
 
 
 
 
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HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
OPERATIVE DAT, REV  E 20110526 
FOR 
EDWARDS 
USE ONLY 
Clinical Review: 
Data Management: 
 
First Review: 
Second Review: (optional) 
First Data Entry: 
Second Data Entry: 
Subevent #  
(optional) 
By:   
By: 
By: 
By: 
Date: __ __ __/__ __/__ __ __ __ 
Date:__ __ __/__ __/__ __ __ __ 
Date: __ __ __/__ __/__ __ __ __ 
Date: __ __ __/__ __/__ __ __ __ 
 
 
 
7m.  Anatomic Fit of Valve 
 
 
  Restores Native Saddle Shape 
 
 
  Reduces / Flattens Saddle Shape 
 
 
  Other, specify:  _____________________________________________________________ 
 
 7n.  Coaptation of Leaflets After Seating in Annulus 
 
 
  Complete 
 
 
  Incomplete (Explain):___________________________________________________________ 
 
 
 
8. 
CONDITION OF THE VALVE BEING REPLACED: 
       YES  NO 
 
   
 Calcification 
 
   
  Perforation 
 
   
  Myxomatous 
 
   
  Vegetation 
 
   
  Fusion 
 
   
  Other, specify: ____________________________ 
9. 
SURGICAL APPROACH: 
 
   Full Sternotomy 
 
   Ministernotomy 
 
   Other  (Specify): ___________________________ 
 
10. 
Total Cross Clamp Time of the Aorta 
 
 
 
(min) 
 
Pump Time 
 
 
 
(min) 
 
11. DIFFICULTY WEANING FROM BYPASS: 
 
   No 
   Yes  (Please complete Adverse Events Form):   

 
 
 
 
 
Study Number 2006-05 
Carpentier-Edwards PERIMOUNT Magna Mitral Valve 
Operative Data 
FORM 3 
 
PAGE  5 OF 5 
 
Patient Study ID # 2 0 0 6 0 5 
 
 
 
       
        Clinic # 
 
 
 
 
 
 
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HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
OPERATIVE DAT, REV  E 20110526 
FOR 
EDWARDS 
USE ONLY 
Clinical Review: 
Data Management: 
 
First Review: 
Second Review: (optional) 
First Data Entry: 
Second Data Entry: 
Subevent #  
(optional) 
By:   
By: 
By: 
By: 
Date: __ __ __/__ __/__ __ __ __ 
Date:__ __ __/__ __/__ __ __ __ 
Date: __ __ __/__ __/__ __ __ __ 
Date: __ __ __/__ __/__ __ __ __ 
 
 
12. CONCOMITANT PROCEDURES 
      YES  NO  
      
     
 Coronary Artery Bypass Grafting  (Number of Grafts):   ______________________ 
 
     
 Aneurysm Repair 
 
     
 Permanent Pacemaker 
 
     
 Aortic Valve Replacement (Model Number):  __________________ Valve size: __________ mm 
 
     
  Aortic Valve / Annulus Repair  
 
 
 
  With Annuloplasty Ring / Band  
 
 
 
  Without Annuloplasty Ring / Band  
 
      
 Pulmonic Valve / Annulus Repair   
 
 
 
  With Annuloplasty Ring / Band  
 
 
 
  Without Annuloplasty Ring / Band  
 
     
  Tricuspid Valve / Annulus Repair  
 
 
 
  With Annuloplasty Ring / Band    
 
 
 
  Without Annuloplasty Ring / Band  
 
    
 Ablation 
 
    
 Maze Procedure 
 
    
 Occlusion of Left Atrial Appendage 
 
    
 Occlusion of Right Atrial Appendage 
 
    
 Other, specify: ______________________ 
13. WERE THERE ANY INTRA-OPERATIVE ADVERSE EVENTS  
  No     
 Yes: (Please complete Adverse Events CRF) 
 
14. COMMENTS: ___________________________________________________________________________________ 
____________________________________________________________________________________________ 
____________________________________________________________________________________________ 
 
 
 
 
 
I HAVE  R E VIE WE D AND AGR E E  WITH ALL DATA E NTE R E D ON THIS  FOR M 
                                                                                                                                                                                DATE SIGNED 
  
 
  
 
 
 
 
 
 
 
 
INVESTIGATOR SIGNATURE 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 

  
 
 
 
STUDY NUMBER 2006-05 
CARPENTIER-EDWARDS PERIMOUNT MAGNA MITRAL EASE 
DISCHARGE DATA 
FORM 4.0 
PAGE 1 OF 2 
 
Patient Study ID # 2 0 0 6 0 5 
 
 
 
  
        Clinic # 
 
 
  
 
 
 
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HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
DISCHARGE DATA REV E 20110526 
FOR 
EDWARDS 
USE ONLY 
Clinical Review: 
Data Management: 
 
 
First Review: 
Second Review: (optional) 
First Data Entry: 
Second Data Entry: 
Subevent #  
(optional) 
By:   
By: 
By: 
By: 
Date: __ __ __/__ __/__ __ __ __ Date:__ __ __/__ __/__ __ __ __ Date: __ __ __/__ __/__ __ __ __ 
Date: __ __ __/__ __/__ __ __ __ 
 
 
1. PATIENT STATUS: (attach discharge summary) 
 
 ALIVE, DISCHARGED ON:   
 
 
DISCHARGE DATE:      
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
 
 
 
 
 
PATIENT WAS NOT DISCHARGED WITH THIS DEVICE DUE TO: 
 
 
Explant  (Complete explant, adverse event and study exit form) 
 
 
Death  (Complete adverse event and study exit form) 
 
 
Other, specify:    
2. CARDIAC RHYTHM: (Check all that apply) ECG 
 
  Not Done (Complete Protocol Deviation) 
  
  Done 
 
Date: 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
 
 
 
Normal Sinus 
  Atrial Fibrillation 
 
  Atrial Flutter 
  Paced 
 
AV Block    (Indicate degree) 
 
 1st  
  2nd  
 3rd   
 
 
Bundle Branch Block (Indicate branch) 
 Left 
 Right 
 
 
Other, specify: _________________ 
 
 
 
3.  PHYSICAL ASSESSMENT: 
Heart Rate 
 
 
 
(bpm) 
 
 
 
 
Height 
 
 
 
(cm) 
 
 
 
 
Weight 
 
 
 
(kg) 
 
 
 
 
4. COAGULATION PROFILE 
  Not Done (complete Protocol Deviation) 
  Done       Date: 
 
 
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
  NAP (No coumarine derivative treatment) 
 
Int’l Normalized Ratio (INR) 
OR 
 
Partial Thromboplastin Time (PTT) 
 
 
•  
 
 
 
 
 
 
 
 
 
•  
(sec)  
 
 
 

  
 
 
 
STUDY NUMBER 2006-05 
CARPENTIER-EDWARDS PERIMOUNT MAGNA MITRAL EASE 
DISCHARGE DATA 
FORM 4.0 
PAGE 2 OF 2 
 
Patient Study ID # 2 0 0 6 0 5 
 
 
 
  
        Clinic # 
 
 
  
 
 
 
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HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
DISCHARGE DATA REV E 20110526 
FOR 
EDWARDS 
USE ONLY 
Clinical Review: 
Data Management: 
 
 
First Review: 
Second Review: (optional) 
First Data Entry: 
Second Data Entry: 
Subevent #  
(optional) 
By:   
By: 
By: 
By: 
Date: __ __ __/__ __/__ __ __ __ Date:__ __ __/__ __/__ __ __ __ Date: __ __ __/__ __/__ __ __ __ 
Date: __ __ __/__ __/__ __ __ __ 
 
 
5. ANTITHROMBOEMBOLIC THERAPY:  (Check all that apply) 
 
 
 
   None 
 
   Anticoagulants (Heparin, Coumarine Derivates) 
 
   Antiplatelets (Clopidogrel, Dipyridamole, Ticlopidine, Prasugrel) 
               
  Aspirin (Acetylsalicylic Acid) 
 
   Other, specify:________________________ 
        
6.   WERE THERE ANY ADVERSE EVENTS? (Not including Intra-operative complications – Complete AE Form) 
 
  No  
   Yes  
Comments:  ____________________________________________________________________________________ 
________________________________________________________________________________________________ 
________________________________________________________________________________________________ 
7.   ECHOCARDIOGRAPHY:   
 
  
 No, not performed (Complete Protocol Deviation Data)  
 
  
 Yes, performed (Complete Echo Tracking Form and send to Core Lab with Media) 
 
 
 
 
 
 
 
 
 
 
 
 
I HAVE  R E VIE WE D AND AGR E E  WITH ALL DATA E NTE R E D ON THIS  FOR M 
                                                                                                                                                                                DATE SIGNED 
  
 
  
 
 
 
 
 
 
 
 
INVESTIGATOR SIGNATURE 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
 

  
STUDY NUMBER 2006-05 
CARPENTIER-EDWARDS PERIMOUNT MAGNA MITRAL VALVE 
ASSESSMENT DATA 
FORM 5.0 
PAGE 1 OF 4 
 
 
 
 
Patient Study ID # 2 0 0 6 0 5 
 
 
 
       
        Clinic # 
 
 
  
 
 
 
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                         HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
                                  ASSESSMENT DATA REV E 20110526 
FOR 
EDWARDS 
USE ONLY 
Clinical Review: 
Data Management: 
 
First Review: 
Second Review: (optional) 
First Data Entry: 
Second Data Entry: 
Subevent #  
(optional) 
By:   
By: 
By: 
By: 
Date: __ __ __/__ __/__ __ __ __ Date:__ __ __/__ __/__ __ __ __ Date: __ __ __/__ __/__ __ __ __ Date: __ __ __/__ __/__ __ __ __ 
 
1. ASSESSMENT DATE:     
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
       2.   FOLLOW-UP INTERVAL: 
 
6 Month  (3 – 6 months) 
 
5 Years  (59 – 61 months) 
 
1 Year  (11 – 13 months) 
 
6 Years  (71 – 73 months) 
 
2 Years  (23 – 25 months) 
 
7 Years  (83 – 85 months) 
 
3 Years  (35 – 37 months) 
 
8 Years  (95 – 97 months) 
 
4 Years  (47 – 49 months) 
 
Other, specify:   
 
 Months 
 Years 
 
   3.    VISIT STATUS: 
 
Conducted visit: (Check one only) 
 
 
  Office Visit / Clinic / Outpatient/ Hospital 
 
 
  In-patient Admission 
 
 
  Phone (from whom):____________________ 
 
 
 
 
 
 
specify relationship 
 
 
  Letter (from whom):____________________ 
 
 
 
 
 
 
specify relationship 
 
 
OR 
 
Missed visit:  (Check Only One) 
 
 
  Scheduled, patient missed 
 
 
  Unable to contact patient 
 
 
  Other (Explain): _______________________ 
 
 
   4.   PATIENT STATUS: 
 
 
Alive  
 
 
 
 
Explant  (Complete explant, adverse event and study exit form) 
 
 
 
Death  (Complete adverse event and study exit form) 
 
 
 
Withdrawn  (Reason):  __________________ 
 
 
 
Other, specify:   
__________________ 

  
STUDY NUMBER 2006-05 
CARPENTIER-EDWARDS PERIMOUNT MAGNA MITRAL VALVE 
ASSESSMENT DATA 
FORM 5.0 
PAGE 2 OF 4 
 
 
 
 
Patient Study ID # 2 0 0 6 0 5 
 
 
 
       
        Clinic # 
 
 
  
 
 
 
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                         HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
                                  ASSESSMENT DATA REV E 20110526 
FOR 
EDWARDS 
USE ONLY 
Clinical Review: 
Data Management: 
 
First Review: 
Second Review: (optional) 
First Data Entry: 
Second Data Entry: 
Subevent #  
(optional) 
By:   
By: 
By: 
By: 
Date: __ __ __/__ __/__ __ __ __ Date:__ __ __/__ __/__ __ __ __ Date: __ __ __/__ __/__ __ __ __ Date: __ __ __/__ __/__ __ __ __ 
 
 
  ASSESSMENT DATE:   
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
5.   PHYSICAL ASSESSMENT: 
Heart Rate 
 
 
 
(bpm) 
 
 
 
 
 
Weight 
 
 
 
(kg) 
 
 
 
 
 
Blood Pressure 
 
 
 
 
 
 
 
mmHg 
6.  PREOPERATIVE CARDIAC RHYTHM (Check all that apply)  ECG 
  Not Done    (Complete Protocol Deviation) 
  Done 
 
 
Date: 
 
 
 
 
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
 
 
 
 
 
Normal Sinus 
  Atrial Fibrillation 
 
  Atrial Flutter 
  Paced 
 
AV Block    (Indicate degree) 
 
 1st  
  2nd  
 3rd   
 
 
Bundle Branch Block (Indicate branch) 
 
 Left 
 Right 
 
 
Other, specify: _________________ 
 
 
 
 
    7.  NYHA FUNCTIONAL CLASS: 
 
 
 Class I 
   
 Class II       
 Class III        
 Class IV 
 NAV 
 
           8.  ANTITHROMBOEMBOLIC THERAPY: (Check all that apply) 
   None 
 
   Anticoagulants (Heparin, Coumarine Derivates) 
 
   Antiplatelets (Clopidogrel, Dipyridamole, Ticlopidine, Prasugrel) 
               
  Aspirin (Acetylsalicylic Acid) 
 
   Other, specify:________________________ 
 
     9.  WERE THERE ANY ADVERSE EVENTS? (Since Last Assessment including Death and Explant) 
             
    No           
    Yes 
     10.  ECHOCARDIOGRAPHY:  (Required at 6-month, 1, 2, 4, 6 and 8  year follow-up visits) 
   
 No, not performed (Complete Protocol Deviation Data)  
     
   Yes, performed (Complete Echo Tracking Form and send to Core Lab with Media) 
   
 Not required at this visit  

  
STUDY NUMBER 2006-05 
CARPENTIER-EDWARDS PERIMOUNT MAGNA MITRAL VALVE 
ASSESSMENT DATA 
FORM 5.0 
PAGE 3 OF 4 
 
 
 
 
Patient Study ID # 2 0 0 6 0 5 
 
 
 
       
        Clinic # 
 
 
  
 
 
 
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                         HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
                                  ASSESSMENT DATA REV E 20110526 
FOR 
EDWARDS 
USE ONLY 
Clinical Review: 
Data Management: 
 
First Review: 
Second Review: (optional) 
First Data Entry: 
Second Data Entry: 
Subevent #  
(optional) 
By:   
By: 
By: 
By: 
Date: __ __ __/__ __/__ __ __ __ Date:__ __ __/__ __/__ __ __ __ Date: __ __ __/__ __/__ __ __ __ Date: __ __ __/__ __/__ __ __ __ 
 
 
ASSESSMENT DATE:     
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
  11.  BLOOD DATA 
  Not Done (complete Protocol Deviation) 
  Done       Date: 
 
 
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
PREOPERATIVE COAGULATION PROFILE:   
 
NAP (No coumarine derivative treatment) 
 
Int’l Normalized Ratio (INR) 
OR 
 
Partial Thromboplastin Time (PTT) 
 
 
•  
 
 
 
 
 
 
 
 
 
•  
(sec)  
 
 
  
COMPLETE SECTION A 
A.  
BLOOD PARAMETER 
VALUE 
UNITS 
WITHIN NORMAL 
RANGE? 
IF NO, CLINICALLY 
SIGNIFICANT? 
YES 
NO 
YES 
NO 
WHITE BLOOD CELLS 
 
(x 103/µL) 
 
 
 
 
RED BLOOD CELLS 
 
(x 106/µL) 
 
 
 
 
HEMOGLOBIN 
 
(gm/dL) 
 
 
 
 
HEMATOCRIT 
 
(%) 
 
 
 
 
RETICULOCYTES 
 
(%) 
 
 
 
 
PLATELET COUNT 
 
(x 103/µL) 
 
 
 
 
 
 
 
COMPLETE SECTION B OR C 
B.  
BLOOD 
PARAMETER 
VALUE 
UNITS 
WITHIN NORMAL 
RANGE? 
IF NO, CLINICALLY 
SIGNIFICANT? 
YES 
NO 
YES 
NO 
PLASMA FREE 
HEMOGLOBIN 
 
(mg/dL) 
 
 
 
 
 

  
STUDY NUMBER 2006-05 
CARPENTIER-EDWARDS PERIMOUNT MAGNA MITRAL VALVE 
ASSESSMENT DATA 
FORM 5.0 
PAGE 4 OF 4 
 
 
 
 
Patient Study ID # 2 0 0 6 0 5 
 
 
 
       
        Clinic # 
 
 
  
 
 
 
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                         HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
                                  ASSESSMENT DATA REV E 20110526 
FOR 
EDWARDS 
USE ONLY 
Clinical Review: 
Data Management: 
 
First Review: 
Second Review: (optional) 
First Data Entry: 
Second Data Entry: 
Subevent #  
(optional) 
By:   
By: 
By: 
By: 
Date: __ __ __/__ __/__ __ __ __ Date:__ __ __/__ __/__ __ __ __ Date: __ __ __/__ __/__ __ __ __ Date: __ __ __/__ __/__ __ __ __ 
 
 
  ASSESSMENT DATE:   
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
OR 
 
C.  
BLOOD 
PARAMETER 
VALUE 
UNITS 
WITHIN NORMAL 
RANGE? 
IF NO, CLINICALLY 
SIGNIFICANT? 
YES 
NO 
YES 
NO 
HAPTOGLOBIN 
 
(mg/dL) 
 
 
 
 
SERUM LDH 
 
(U/L) 
 
 
 
 
 
 
12. QUALITY OF LIFE SURVEY:  (Required at 6 Month Follow-up Only) 
 
 Not Appplicable at this follow-up interval  
 
 No, patient did not complete at 6 Month  (Complete Protocol Deviation Data) 
 
 Yes, patient completed  (Complete QOL Survey Data) 
 
 
 
 
 
 
 
I HAVE REVIEWED AND AGREE WITH ALL DATA ENTERED ON THIS FORM 
 
  
 
DATE SIGNED  
 
 
 
 
 
 
 
 
INVESTIGATOR SIGNATURE 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 

STUDY NUMBER 2006-05 
CARPENTIER-EDWARDS PERIMOUNT MAGNA MITRAL VALVE  
ADVE R S E  E VE NT 
FOR M 6.0 
PAGE  1 OF 2 
 
 
Patient Study ID#  2 0 0 6 0 5 
-  
 
 
 
 
 
 
 
Clinic # 
 
 
 
 
 
 
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HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
ADVERSE EVENT DATA REV E 20110526 
FOR 
EDWARDS 
USE ONLY 
CLINICAL REVIEW: 
DATA MANAGEMENT: 
 
FIRST REVIEW: 
SECOND REVIEW: (OPTIONAL) 
FIRST DATA ENTRY: 
SECOND DATA ENTRY: 
SUBEVENT #  
(OPTIONAL) 
BY:   
BY: 
BY: 
BY: 
DATE: __ __ __/__ __/__ __ __ __ 
DATE:__ __ __/__ __/__ __ __ __ 
DATE: __ __ __/__ __/__ __ __ __ 
DATE: __ __ __/__ __/__ __ __ __ 
 
RECORD ONLY ONE ADVERSE EVENT PER FORM 
1. 
EVENT ONSET DATE 
 
 
 
 
 
 
 
 
 
 
 INITIAL REPORT 
 FINAL REPORT 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
 
 
2. 
TIMING OF EVENT ONSET 
 PRE-OPERATIVE 
 INTRA-OPERATIVE 
 
 POST-OPERATIVE 
 
3. 
EVENT NAME (SEE EVENT LISTING) 
 
 
4. 
EVENT SUMMARY 
 
 
 
 
 
 
5. 
METHOD OF DETECTION (CHECK ALL THAT APPLY) 
 LAB FINDING 
 IMAGING 
 ECG 
 AUTOPSY 
 OBSERVATION 
 OTHER (SPECIFY)  
 EXAM 
 NONE AVAILABLE 
 
 
 
6. 
CAUSALITY 
 
7. MEDICATION CONTRIBUTING TO EVENT? 
SURGICAL PROCEDURE 
 YES 
 NO 
 UNDETERMINED 
CHECK “YES” ONLY IF MED CONTRIBUTED TO  EVENT 
STUDY VALVE 
 YES 
 NO 
 UNDETERMINED 
 YES 
 NO 
STUDY VALVE PROCEDURE 
 YES 
 NO 
 UNDETERMINED 
IF BLEEDING EVENT CHECK CATEGORY BELOW 
USE ERROR 
 YES 
 NO 
 UNDETERMINED 
 ANTICOAGULANT MED 
DEFICIENCY IN INSTRUCTIONS 
 YES 
 NO 
 UNDETERMINED 
 ANTIPLATELET MED 
DEVICE DEPLOYMENT ISSUE 
 YES 
 NO 
 UNDETERMINED 
 ASPIRIN 
OTHER* 
 YES 
 NO 
 UNDETERMINED 
 CO-ENZYME Q10 
*IF “OTHER”  IS YES, PROVIDE REASON: _______________________________________________________ 
 OTHER (SPECIFY) __________________ 
______________________________________________________________________________________________________________________________________________ 
 
8. 
SERIOUS ADVERSE EVENT 
 YES 
 NO 
 
 RESULTED IN DEATH 
 RESULTED IN LIFE-THREATENING ILLNESS OR INJURY 
 RESULTED IN PERMANENT IMPAIRMENT 
 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 OTHER (SPECIFY) 
 
 
9. 
UNANTICIPATED* 
 YES 
 NO 
 NOT APPLICABLE 
 
*QUESTION ONLY APPLIES IF EVENT IS DEEMED RELATED TO STUDY VALVE OR STUDY VALVE PROCEDURE OR RELATIONSHIP IS UNDETERMINED 

STUDY NUMBER 2006-05 
CARPENTIER-EDWARDS PERIMOUNT MAGNA MITRAL VALVE  
ADVE R S E  E VE NT 
FOR M 6.0 
PAGE  2 OF 2 
 
 
Patient Study ID#  2 0 0 6 0 5 
-  
 
 
 
 
 
 
 
Clinic # 
 
 
 
 
 
 
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HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
ADVERSE EVENT DATA REV E 20110526 
FOR 
EDWARDS 
USE ONLY 
CLINICAL REVIEW: 
DATA MANAGEMENT: 
 
FIRST REVIEW: 
SECOND REVIEW: (OPTIONAL) 
FIRST DATA ENTRY: 
SECOND DATA ENTRY: 
SUBEVENT #  
(OPTIONAL) 
BY:   
BY: 
BY: 
BY: 
DATE: __ __ __/__ __/__ __ __ __ 
DATE:__ __ __/__ __/__ __ __ __ 
DATE: __ __ __/__ __/__ __ __ __ 
DATE: __ __ __/__ __/__ __ __ __ 
 
EVENT ONSET DATE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
 
 
 
 
 
 
10. INTERVENTION 
(MULTIPLE RESPONSS POSSIBLE) 
 
 NONE 
 
 PROLONGED HOSPITALIZATION 
 
 RE-HOSPITALIZATION REQUIRED 
 
 CARDIOVERSION 
 
 TRANSFUSION 
 MEDICATION GIVEN, SPECIFY 
 
 
 
 
 
 
 
 
 
 
 
 
 PACEMAKER/ICD IMPLANT (NOT PLANNED PRIOR TO AVR  - PROVIDE DATE) 
 
 
 
 
 
 
 
 
 
  
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 SURGICAL INTERVENTION, REOP ON STUDY VALVE OR OTHER INTERVENTION ON STUDY VALVE  (SEE EXPLANT REPORT) 
 
 
 
 
 
 
 
 
 
 
 
 OTHER INVASIVE INTERVENTION  (RE-OP NON VALVE RELATED) 
 
 
 
 
 
 
 
 
 
 (SPECIFY BELOW – PROVIDE DATE) 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
 SPECIFY OTHER INVASIVE INTERVENTION  
 
11. OUTCOME 
 
 ONGOING 
 UNRESOLVED 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 
 EXPLANT (COMPLETE EXPLANT FORM) 
 
 
 
 DEATH (COMPLETE EXIT FORM) 
DATE: 
 
 
 
 
 
 
 
 
 
  
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
I HAVE  R E VIE WE D AND AGR E E  WITH ALL DATA E NTE R E D ON THIS  FOR M 
 
  
 
DATE SIGNED 
 
 
 
 
 
 
 
 
 
INVESTIGATOR SIGNATURE 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 

 
 
Study Number 2006-05 
Carpentier-Edwards PERIMOUNT Magna Mitral Valve 
Explant Device Evaluation 
FORM 8 
Page 1 of 1 
 
Patient Study ID #  
2 
0 
0 
6 
0 
5 
 
 
 
 
 
Clinic #  
 
 
 
 
 
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HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
RECOVERED DEVICE EVALUATION, REV E 20110526 
FOR 
EDWARDS 
USE ONLY 
Clinical Review: 
Data Management: 
 
First Review: 
Second Review: (optional) 
First Data Entry: 
Second Data Entry: 
Subevent #  
(optional) 
By:   
By: 
By: 
By: 
Date: __ __ __/__ __/__ __ __ __ Date:__ __ __/__ __/__ __ __ __ Date: __ __ __/__ __/__ __ __ __ 
Date: __ __ __/__ __/__ __ __ __ 
 
 
1. DATE OF EXPLANT:     
 
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
 
 
           
 
 
2. DEVICE WAS EXPLANTED: (Complete adverse event and study exit form) 
 At re-operation 
 At autopsy 
 Other:_________________________________ 
3. REASON FOR EXPLANT: 
 SVD  
 NSVD 
 
 Other, Specify: _____________________ 
4. DEVICE WAS RETURNED TO EDWARDS: 
 YES  
 NO 
 
5.  REPLACEMENT VALVE:    
  Not Applicable (Autopsy)  
 
6. DEVICE EVALUATION: 
 
 
No 
Yes 
Comment 
Thrombus 
 
 
 
Vegetation 
 
 
 
Suture Interference 
 
 
 
Instrument Trauma 
 
 
 
Calcification 
 
 
 
Fibrosis 
 
 
 
Dehiscence 
 
 
 
Pannus 
 
 
 
Other 
 
 
 
 
 
COMMENTS: 
 
 
 
 
 
 
I HAVE  R E VIE WE D AND AGR E E  WITH ALL DATA E NTE R E D ON THIS  FOR M 
 
                                                                                                                                                                                DATE SIGNED 
  
 
 
 
 
 
 
 
 
 
 
 
INVESTIGATOR SIGNATURE 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
 
 
 
Manufacturer 
 
Size 

 
 
Study Number 2006-05 
Carpentier-Edwards PERIMOUNT Magna Mitral Valve 
Echocardiography Tracking 
Data FORM 9 
 
Page 1 of 2 
 
Patient Study ID #  2 
0 
0 
6 
0 
5 
 
 
 
 
Patient Initials (First, Last)  
 
 
Clinic #   
 
 
 
 
 
 
Please Provide The Following Information: 
 
1.  ECHO DATE:     
 
 
 
 
 
 
 
 
 
 
 
 
 
             D      D      M     M      M    Y       Y       Y      Y 
 
2.  TIME PERIOD: (Required preoperatively, at discharge, 6-months, 1, 2, 4, 6 and 8 year follow-up visits) 
     
 
Preoperatively (≤ 6 months prior to implant) 
 
4 Years (47 – 49 months) 
 
Discharge or 30 days 
 
6 Years (71 – 73 months) 
 
1 Year (11 – 13 months) 
 
8 Years (95 – 97 months)) 
 
2 Years (23 – 25 months) 
 
Other, specify:   
 
 Months 
 Years 
 
4 Years  (47 – 49 months) 
 
3.  ECHO RECORDED ON (MEDIA): 
 
 
 Tape    
 CD 
 
 
 MOD    
 DVD 
4.  REASON FOR ECHO: 
 
 Per protocol 
 
 Symptomatic, study valve related 
 
 Symptomatic, non-study valve related 
 
 Other, specify:  
 
 
 
 
 
5.  PHYSICAL ASSESSMENT: 
 
 
 
 
 
 
 
DATE MEDIA SENT:     
 
 
 
 
 
 
 
 
 
 
 
 
 
 D      D      M     M      M    Y       Y       Y      Y 
 
 
 
 
 
(OR COLLECTED BY MONITOR) 
 
 
 
Heart Rate 
 
 
 
(bpm) 
 
 
 
 
 
 
Height 
 
 
 
(cm) 
 
 
 
 
 
 
Weight 
 
 
 
(kg) 
 
 
 
 
 
 
Blood Pressure 
 
 
 
 
 
 
 
mmHg 
 

 
 
I have reviewed and approved all information on this form.  (Investigator’s Signature) Date                                         
 
 
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PROPRIETARY DATA:  This document and information contained herein may not be reproduced, used or disclosed without written permission of Baxter Healthcare Corporation  
 
 
CardioVascular Group, Clinical Affairs 
echo log.doc 6/3/11 
FOR 
Clinical Audit 
Tracked:  _________ 
BAXTER 
First Audit 
Second Audit 
Data Entered 
USE 
By:   
By: 
By: 
Date:  __ __ / __ __ / __ __ __ __ 
ONLY 
Date:  __ __ / __ __ / __ __ __ __ 
Date:  __ __ / __ __ / __ __ __ __ 
By: 
Date:  __ __ / __ __ / __ __ __ __ 
 
 

 
 
STUDY NUMBER 2006-05 
CARPENTIER-EDWARDS PERIMOUNT MAGNA MITRAL VALVE  
PROTOCOL DEVIATION 
FOR M 11.0 
PAGE  _____OF_____ 
 
Patient Study 
ID#  
2 0 0 6 0 5 
- 
 
 
 
 
 
 
 
 
Clinic # 
 
 
 
 
 
 
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HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
DEVIATION  DATE  REV E 20110526 
 
FOR 
EDWARDS 
USE ONLY 
CLINICAL REVIEW: 
DATA MANAGEMENT: 
 
FIRST REVIEW: 
SECOND REVIEW: (OPTIONAL) 
FIRST DATA ENTRY: 
SECOND DATA ENTRY: 
SUBEVENT #  
(OPTIONAL) 
BY:   
BY: 
BY: 
BY: 
DATE: __ __ __/__ __/__ __ __ __ 
DATE:__ __ __/__ __/__ __ __ __ 
DATE: __ __ __/__ __/__ __ __ __ 
DATE: __ __ __/__ __/__ __ __ __ 
 
 
COMPLETE FORM IN THE EVENT OF DEVIATION FROM STUDY PROTOCOL 
PROTOCOL DEVIATION CODES CAN BE FOUND IN CRF COMPLETION INSTRUCTIONS 
1. DEVIATION CODE 
 
 
DATE OF DEVIATION 
 
 
 
 
 
 
 
 
 
 OTHER, SPECIFY 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
REASON: 
 
 
 
2. DEVIATION CODE 
 
 
DATE OF DEVIATION 
 
 
 
 
 
 
 
 
 
 OTHER, SPECIFY 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
REASON: 
 
 
 
3. DEVIATION CODE 
 
 
DATE OF DEVIATION 
 
 
 
 
 
 
 
 
 
 OTHER, SPECIFY 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
REASON: 
 
 
 
4. DEVIATION CODE 
 
 
DATE OF DEVIATION 
 
 
 
 
 
 
 
 
 
 OTHER, SPECIFY: 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
REASON: 
 
 
 
5. DEVIATION CODE 
 
 
DATE OF DEVIATION 
 
 
 
 
 
 
 
 
 
 OTHER, SPECIFY: 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
REASON: 
 
 
I HAVE  R E VIE WE D AND AGR E E  WITH ALL DATA E NTE R E D ON THIS  FOR M 
 
DATE 
 
 
 
 
 
 
 
 
 
INVESTIGATOR SIGNATURE 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 

Study Number 2006-05 
Carpentier-Edwards PERIMOUNT Magna Mitral Valve 
QOL Survey (EQ-5D) 
FORM 12 
 
Page 1 of 1 
 
Patient Study ID #  
2 
0 
0 
6 
0 
5 
 
 
 
 
 
Clinic #   
 
 
 
 
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PROPRIETARY DATA:  THIS DOCUMENT AND INFORMATION CONTAINED HEREIN MAY NOT BE REPRODUCED, USED, OR DISCLOSED WITHOUT WRITTEN PERMISSION OF EDWARDS LIFESCIENCES,  
 
HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
QUALITY OF LIFE  SURVEY  REV E 20110526 
FOR 
EDWARDS 
USE ONLY 
Clinical Review: 
Data Management: 
 
First Review: 
Second Review: (optional) 
First Data Entry: 
Second Data Entry: 
Subevent #  
(optional) 
By:   
By: 
By: 
By: 
Date: __ __ __/__ __/__ __ __ __ Date:__ __ __/__ __/__ __ __ __ Date: __ __ __/__ __/__ __ __ __ 
Date: __ __ __/__ __/__ __ __ __ 
 
Date of Assessment:   
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
Assessment Interval: 
 
Baseline/Pre-operative 
 
6 month 
1. Mobility  (Indicate which statement the subject marked on the survey) 
 
I have no problem in walking about 
 
I have some problems in walking about 
 
I am confined to bed 
2. Self-Care  (Indicate which statement the subject marked on the survey) 
 
I have no problem with self-care 
 
I have some problems washing or dressing myself 
 
I am unable to wash or dress myself 
3. Usual Activities  (Indicate which statement the subject marked on the survey) 
 
I have no problem with performing my usual activities 
 
I have some problems with performing my usual activities 
 
I am unable to perform my usual activities 
4. Pain / Discomfort  (Indicate which statement the subject marked on the survey) 
 
I have no pain or discomfort 
 
I have moderate pain or discomfort 
 
I have extreme pain or discomfort 
5. Anxiety / Depression  (Indicate which statement the subject marked on the survey) 
 
I am not anxious or depressed 
 
I am moderately anxious or depressed 
 
I am extremely anxious or depressed 
6. Overall state  (Indicate how the subject rated their overall heath today) 
  
Score: __________ 
Comment:______________________________________________________________________________ 
_______________________________________________________________________________________ 
_______________________________________________________________________________________ 
I HAVE  R E VIE WE D AND AGR E E  WITH ALL DATA E NTE R E D ON THIS  FOR M 
                                                                                                                                                                                DATE SIGNED 
  
 
  
 
 
 
 
 
 
 
 
INVESTIGATOR SIGNATURE 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 

Study Number 2006-05 
Carpentier-Edwards PERIMOUNT Magna Mitral Valve 
Study Exit Data 
FORM 13 
 
Page 1 of 1 
 
Patient Study ID #  
2 
0 
0 
6 
0 
5 
 
 
 
 
 
Clinic #   
 
 
 
 
White and Yellow:  Return to Edwards Lifesciences, Clinical Affairs    Pink:  Retain for your Records 
PROPRIETARY DATA:  THIS DOCUMENT AND INFORMATION CONTAINED HEREIN MAY NOT BE REPRODUCED, USED, OR DISCLOSED WITHOUT WRITTEN PERMISSION OF EDWARDS LIFESCIENCES  
 
HEART VALVE THERAPY GROUP, CLINICAL AFFAIRS 
STUDY EXIT  REV E 20110526 
FOR 
EDWARDS 
USE ONLY 
Clinical Review: 
Data Management: 
 
First Review: 
Second Review: (optional) 
First Data Entry: 
Second Data Entry: 
Subevent #  
(optional) 
By:   
By: 
By: 
By: 
Date: __ __ __/__ __/__ __ __ __ Date:__ __ __/__ __/__ __ __ __ Date: __ __ __/__ __/__ __ __ __ 
Date: __ __ __/__ __/__ __ __ __ 
 
1. 
 DATE OF LAST PATIENT CONTACT:   
 
 
 
 
 
 
 
 
 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 
 
 
  
 
 
 
 
2. 
REASON FOR STUDY EXIT: 
 
 Screen Failure (Complete Form 1: Patient Selection Data) (Signed ICF and did not receive implant) 
 
 Completed all study assessments  
 
 Terminated by Investigator (specify reason in #4) 
 
Voluntary Withdrawal  
 
 
 
Met enrollment criteria and withdrawn for medical reasons 
 
 
 
Met enrollment criteria and withdrawn for non medical reasons 
 
 Lost to Follow-up (unable to contact)   (Complete Assessment Form) 
 
 Death (Complete adverse event form) 
 
 
 
 Device Explanted (Complete Explant Data)  
 
 Other (specify in #4)    
 
3. 
STUDY INTERVALS COMPLETED: (check all that apply) 
 
 Preoperative Assessment  
 
 3 year follow-up assessment 
 
 Device Implant  
 
 4 year follow-up assessment 
 
 Hospital Discharge 
 
 
 5 year follow-up assessment 
 
 3 – 6 month follow-up assessment  
 6 year follow-up assessment 
 
 1 year follow-up assessment 
 
 7 year follow-up assessment 
 
 2 year follow-up assessment 
 
  8 year follow-up assessment 
 
4. 
DESCRIBE THE PATIENT’S CONDITION AT LAST VISIT: 
_____________________________________________________________________________________________________ 
_____________________________________________________________________________________________________ 
_____________________________________________________________________________________________________ 
_____________________________________________________________________________________________________ 
_____________________________________________________________________________________________________ 
I HAVE  R E VIE WE D AND AGR E E  WITH ALL DATA E NTE R E D ON THIS  FOR M 
                                                                                                                                                                                DATE SIGNED 
  
 
  
 
 
 
 
 
 
 
 
INVESTIGATOR SIGNATURE 
 
D 
D 
M 
M 
M 
Y 
Y 
Y 
Y 
 

Magna Mitral Post Approval Study Protocol 2006-05   
 
 REV I  November 18, 2013  
 
 
 
 
 
 This document and the information contained herein is considered Proprietary and Confidential  
and may not be reproduced, used or disclosed without written permission from Edwards Lifesciences LLC. 
 
 
- pg 75 of 80 - 
17.0  APPENDIX 6: QUALITY OF LIFE SURVEY 
 

 
 
 
Version 1.0  
 
August 2008 
 
 
Web:  www.euroqol.org 
Email: userinformationservice@euroqol.org 
Prepared by:  
 
Mark Oppe 
Rosalind Rabin 
Frank de Charro  
 
On behalf of the EuroQoL Group 
User Guide 

 
 
 
 
 
Table of contents 
 
 
1. INTRODUCTION...........................................................................................................3 
EUROQOL GROUP ..........................................................................................................3 
EQ-5D ...........................................................................................................................4 
WHAT IS A HEALTH STATE?..............................................................................................7 
VERSIONS OF EQ-5D......................................................................................................8 
2. SCORING THE EQ-5D DESCRIPTIVE SYSTEM ........................................................9 
3. SCORING THE EQ VAS.............................................................................................10 
4. CONVERTING EQ-5D STATES TO A SINGLE SUMMARY INDEX .........................11 
5. ORGANISING EQ-5D DATA......................................................................................12 
6. PRESENTING EQ-5D RESULTS...............................................................................13 
HEALTH PROFILES.........................................................................................................13 
EQ VAS.......................................................................................................................15 
EQ-5D INDEX ...............................................................................................................16 
7. EQ-5D: FREQUENTLY ASKED QUESTIONS...........................................................19 
8. ADDITIONAL INFORMATION....................................................................................22 
 
 
 

 
1. Introduction 
This guide has been developed in order to give users of EQ-5D basic information on 
how to use EQ-5D. Topics include administering the instrument, setting up a 
database for data collected using EQ-5D as well as information about how to present 
the results. Also included are some frequently asked questions dealing with common 
issues regarding the use of EQ-5D and a list of currently available EuroQoL products. 
 
EuroQoL Group 
• 
The EuroQoL Group is a network of international multidisciplinary researchers 
devoted to the measurement of health status. Established in 1987, the EuroQoL 
Group originally consisted of researchers from Europe, but nowadays includes 
members from North America, Asia, Africa, Australia, and New Zealand. The 
Group is responsible for the development of EQ-5D, a preference based measure 
of health status that is now widely used in clinical trials, observational studies and 
other health surveys. 
 
• 
The EuroQoL Group has been holding annual scientific meetings since its 
inception in 1987.  
 
• 
The EuroQoL Group can be justifiably proud of its collective scientific 
achievements over the last 20 years. Research areas include: valuation, EQ-5D 
use in clinical studies and in population surveys, experimentation with the EQ-5D 
descriptive system, computerized applications, interpretation of EQ-5D ratings 
and the role of EQ-5D in measuring social inequalities in self-reported health. 
 
• 
The EuroQoL Group’s website (www.euroqol.org) contains detailed information 
about EQ-5D, guidance for users, a list of available language versions, EQ-5D 
references and contact details. 
 
 
 
3 
 

 
EQ-5D 
EQ-5D is a standardised measure of health status developed by the EuroQoL Group 
in order to provide a simple, generic measure of health for clinical and economic 
appraisal1. Applicable to a wide range of health conditions and treatments, it provides 
a simple descriptive profile and a single index value for health status that can be 
used in the clinical and economic evaluation of health care as well as in population 
health surveys (Figure 1).
 
EQ-5D is designed for self-completion by respondents and is ideally suited for use in 
postal surveys, in clinics, and in face-to-face interviews. It is cognitively 
undemanding, taking only a few minutes to complete. Instructions to respondents are 
included in the questionnaire.  
 
EQ-5D essentially consists of 2 pages - the EQ-5D descriptive system (page 2) and 
the EQ visual analogue scale (EQ VAS) (page 3). The EQ-5D descriptive system 
comprises the following 5 dimensions: mobility, self-care, usual activities, 
pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, 
some problems, severe problems. The respondent is asked to indicate his/her health 
state by ticking (or placing a cross) in the box against the most appropriate statement 
in each of the 5 dimensions. This decision results in a 1-digit number expressing the 
level selected for that dimension. The digits for 5 dimensions can be combined in a 5-
digit number describing the respondent’s health state. It should be noted that the 
numerals 1-3 have no arithmetic properties and should not be used as a 
cardinal score. This current 3-level, 5-dimensional format of EQ-5D will remain 
unchanged for the immediate future. However a EuroQoL task force is developing a 
5-level version. This should become available around 2009. 
 
The EQ VAS records the respondent’s self-rated health on a vertical, visual analogue 
scale where the endpoints are labelled ‘Best imaginable health state’ and ‘Worst 
imaginable health state’. This information can be used as a quantitative measure of 
health outcome as judged by the individual respondents. 
 
                                                 
1 EuroQoL Group. EuroQoL-a new facility for the measurement of health-related quality of life. Health 
Policy 1990;16:199-208 
 
 
 
4 
 

 
Figure 1:  EQ-5D (UK English version) 
By placing a tick in one box in each group below, please indicate which statements 
best describe your own health state today. 
 
Mobility 
I have no problems in walking about 
 
I have some problems in walking about 
 
I am confined to bed 
 
 
Self-Care 
I have no problems with self-care 
 
I have some problems washing or dressing myself 
 
I am unable to wash or dress myself 
 
 
Usual Activities (e.g. work, study, housework, family or 
leisure activities) 
I have no problems with performing my usual activities 
 
I have some problems with performing my usual activities 
 
I am unable to perform my usual activities 
 
 
Pain/Discomfort 
I have no pain or discomfort 
 
I have moderate pain or discomfort 
 
I have extreme pain or discomfort 
 
 
Anxiety/Depression 
I am not anxious or depressed 
 
I am moderately anxious or depressed 
 
I am extremely anxious or depressed 
 
 
 
5 
 

To help people say how good or bad a health state is, we 
have drawn a scale (rather like a thermometer) on which 
the best state you can imagine is marked 100 and the 
worst state you can imagine is marked 0.
We would like you to indicate on this scale how good or 
bad your own health is today, in your opinion. Please do 
this by drawing a line from the box below to whichever 
point on the scale indicates how good or bad your health 
state is today.
Your own
health state
today
6

 
Versions of EQ-5D 
EQ-5D in different languages 
Currently there are more than 100 translated versions of EQ-5D. If you want to know 
if there is an EQ-5D version appropriate for your country, please consult the website. 
 
All translations/adaptations of EQ-5D are produced using a standardised translation 
protocol that conforms to internationally recognized guidelines. These guidelines aim 
to ensure semantic and conceptual equivalence and involve a forward/backward 
translation process and lay panel assessment. Only the EuroQoL Group Executive 
Office can give permission for a translation to be performed and translations can only 
be stamped as official if they are performed in cooperation with EuroQoL Group 
reviewers.  
 
Alternative modes of administration 
EQ-5D was primarily designed for self-completion by the patient or respondent. 
However the Group has brief guidelines for the following alternative modes of 
administration: 
 
(i) Face-to-face 
(ii) Self-completion in the presence of an interviewer 
(iii) Telephone interview 
(iv) Proxy (asking the proxy to rate how he or she, (i.e. the proxy), would rate the 
subject’s health)  
 
Guidelines for telephone and proxy use are available in a number of different 
languages. 
 
Child versions 
EQ-5D is generally considered suitable for children aged 12 years and over (although 
this may vary in different countries). Currently a EuroQoL Group task force is 
developing a version for children between 7 and 12 years in international English. 
This version is being validated in Swedish, Italian, Spanish and German and these 
versions should become available in 2008.  
 
Please check the EuroQoL website for up-to-date information on the availability of 
EuroQoL products. 
 
 
8 
 

 
4. Converting EQ-5D states to a single summary index 
EQ-5D health states, defined by the EQ-5D descriptive system, may be converted 
into a single summary index by applying a formula that essentially attaches values 
(also called weights) to each of the levels in each dimension. The index can be 
calculated by deducting the appropriate weights from 1, the value for full health (i.e. 
state 11111). Information in this format is useful, for example, in cost utility analysis. 
 
Value sets have been derived for EQ-5D in several countries using the EQ-5D visual 
analogue scale (EQ-5D VAS) valuation technique or the time trade-off (TTO) 
valuation technique. The list of currently available value sets with the number of 
respondents and valuation technique applied is presented in table 1. Most of the EQ-
5D value sets have been obtained using a representative sample of the general 
population, thereby ensuring that they represent the societal perspective. For anyone 
working with EQ-5D data, an essential guide to the Group’s available value sets can 
be found in: EuroQoL Group Monograph series: Volume 2: EQ-5D value sets: 
inventory, comparative review and user guide, recently published by Springer (see 
section 8 for more information). 
 
Table 1: List of available value sets as of May 2007 
Country 
N 
Valuation method 
Belgium 
548 
EQ-5D VAS 
Denmark 
1179 
EQ-5D VAS 
Denmark 
1332 
TTO 
Europe 
6870 
EQ-5D VAS 
Finland 
928 
EQ-5D VAS 
Germany 
339 
EQ-5D VAS 
Germany 
339 
TTO 
Japan 
543 
TTO 
New Zealand 
919 
EQ-5D VAS 
Netherlands 
298 
TTO 
Slovenia 
370 
EQ-5D VAS 
Spain 
294 
EQ-5D VAS 
Spain 
975 
TTO 
UK 
3395 
EQ-5D VAS 
UK 
3395 
TTO 
US 
3773 
TTO 
Zimbabwe 
2384 
TTO 
 
Documents containing the scoring algorithms, information on the valuation studies, 
tables of values for all 243 health states and SPSS and SAS syntax files can be 
ordered from the EuroQoL Executive Office (userinformationservice@euroqol.org). 
 
 
11 
 

 
5. Organising EQ-5D data 
Data collected using EQ-5D can be entered in a database according to the following 
schema: 
 
Variable 
name 
ID 
COUNTRY YEAR MOBILITY SELFCARE ACTIVITY PAIN 
ANXIETY 
Variable 
description 
patient ID 
number 
  
  
1=No 
Problems, 
2=Some 
problems, 
3=Extreme 
problems, 
9=Missing 
value 
1=No 
Problems, 
2=Some 
problems, 
3=Extreme 
problems, 
9=Missing 
value 
1=No 
Problems, 
2=Some 
problems, 
3=Extreme 
problems, 
9=Missing 
value 
1=No 
Problems, 
2=Some 
problems, 
3=Extreme 
problems, 
9=Missing 
value 
1=No 
Problems, 
2=Some 
problems, 
3=Extreme 
problems, 
9=Missing 
value 
Data row 1 
1001 
UK 
2006
2
1
2 
2 
1
Data row 2 
1002 
UK 
2006
1
1
1 
1 
1
 
Variable 
name 
STATE 
EQ_VAS 
SEX 
AGE 
EDU 
METHOD 
SOC_ECON 
Variable 
description 
  
999= 
Missing 
value 
1=male, 
2=female, 
9=Missing 
value 
999= 
Missing 
value 
1=low, 
2=medium, 
3=high, 
9=Missing 
value 
0=postal, 
1=interview, 
2=telephone, 
9=Missing 
value 
1=employed, 
2=retired,      
….., 
9=Missing 
value 
Data row 1 
21221 
80 
1
43
1
0 
1
Data row 2 
21111 
90 
2
24
2
0 
4
 
 
NB: The variable names are just examples. However, the variables for the 5 dimensions of 
the EQ-5D descriptive system should be named 'mobility', 'selfcare', 'activity', 'pain', and 
'anxiety'. If they are given different names the syntax codes containing the value sets that 
are distributed by the EuroQoL Group will not work properly. 
 
 
12 
 

 
6. Presenting EQ-5D results 
Data collected using EQ-5D can be presented in various ways. A basic subdivision 
can be made according to the structure of the EQ-5D: 
 
1. Presenting results from the descriptive system as a health profile 
2. Presenting results of the EQ VAS as a measure of overall self-rated health status 
3. Presenting results from the descriptive system as a weighted index 
 
However, the way results are presented is partly determined by what message you, 
as a researcher, wish to convey to your audience. 
Health profiles 
One way of presenting data as a health profile is by making a table with the 
frequency or the proportion of reported problems for each level for each dimension.  
These tables can be broken down to include the proportions per subgroup, such as 
age, before vs. after treatment, treatment vs. comparator, etc.  
 
Sometimes it is more convenient to dichotomise the EQ-5D levels into 'no problems' 
(i.e. level 1) and 'problems' (i.e. levels 2 and 3), thereby changing the profile into 
frequencies of reported problems. This can be the case, for example, in a general 
population survey where the numbers of reported level 3 problems are very low. 
Tables 2 and 3 are examples of how to present EQ-5D data in tabulated form. The 
data for the tables originates from a general population survey in the UK2. 
                                                 
2Kind P, Dolan P, Gudex C, Williams A. Variations in population health status: results from a United 
Kingdom national questionnaire survey Bmj 1998;316 (7133): 736-41. 
 
 
 
13 
 

 
 
Table 2: Proportion of levels 1, 2 and 3 by dimension and by age group 
  
  
AGE GROUPS 
  
EQ-5D DIMENSION 
18-29 
30-39
40-49 
50-59 
60-69 
70-79 
80+
TOTAL
Level 1 
95.4
92.2
89.7
78.1
70.7
60.2 
43.3
81.6
Level 2 
4.6
7.6
9.9
21.9
29.3
39.8 
56.7
18.3
MOBILITY 
Level 3 
0.0
0.1
0.4
0.0
0.0
0.0 
0.0
0.1
Level 1 
99.1
98.4
95.8
94.8
94.3
92.6 
83.7
95.7
Level 2 
0.9
1.5
4.0
5.2
5.5
7.1 
15.6
4.1
SELF-CARE 
Level 3 
0.0
0.1
0.2
0.0
0.2
0.2 
0.7
0.1
Level 1 
93.3
91.4
89.2
78.1
75.3
73.7 
56.0
83.7
Level 2 
6.3
7.9
9.4
18.8
21.6
22.1 
38.3
14.2
USUAL 
ACTIVITIES 
Level 3 
0.4
0.7
1.5
3.0
3.1
4.2 
5.7
2.1
Level 1 
83.9
80.7
74.1
56.3
53.8
44.0 
39.7
67.0
Level 2 
15.8
17.7
22.8
38.1
40.6
48.4 
49.6
29.2
PAIN / 
DISCOMFORT 
Level 3 
0.3
1.6
3.1
5.6
5.6
7.6 
10.6
3.8
Level 1 
86.5
82.6
81.3
72.8
72.0
74.7 
75.2
79.1
Level 2 
12.6
16.4
16.9
24.4
25.1
22.6 
24.1
19.1
ANXIETY / 
DEPRESSION 
Level 3 
0.9
1.0
1.8
2.8
2.9
2.7 
0.7
1.8
 
Table 3: Frequency of reported problems by dimension and age group 
  
  
AGE GROUPS 
  
EQ-5D DIMENSION 
18-29 
30-39 
40-49 
50-59 
60-69
70-79 
80+
TOTAL
No problems 
643
631
489
362
339
246 
61
2770
MOBILITY 
Problems 
31
53
56
101
140
162 
81
625
No problems 
668
673
522
439
452
378 
119
3251
SELF-CARE 
Problems 
6
11
23
24
27
30 
23
144
No problems 
629
625
486
362
361
301 
80
2842
USUAL 
ACTIVITIES 
Problems 
45
59
59
101
118
107 
62
553
No problems 
566
552
404
261
258
179 
56
2275
PAIN / 
DISCOMFORT 
Problems 
108
132
141
202
221
229 
86
1120
No problems 
583
565
443
337
345
305 
107
2684
ANXIETY / 
DEPRESSION 
Problems 
91
119
102
126
134
103 
35
711
 
In addition to presenting the results in tabulated form, you can also use graphical 
presentations. Two or 3 dimensional bar charts can be used to summarise the results 
in 1 graph, (see figure 2). Figure 2 shows the sum of the proportion of reported level 
2 and level 3 problems for each of the 5 EQ-5D dimensions for 3 distinct age groups. 
Older people reported more problems on all dimensions but the effect of age was 
strongest for mobility and weakest for anxiety/depression. 
 
 
 
14 
 

 
7. EQ-5D: Frequently asked questions 
For what period of time does EQ-5D record health status? 
Self-reported health status captured by EQ-5D relates to the respondent’s situation at 
the time of completion. No attempt is made to summarise the recalled health status 
over the preceding days or weeks, although EQ-5D has been tested in recall mode. 
An early decision taken by the EuroQoL Group determined that health status 
measurement ought to apply to the respondent’s immediate situation - hence the 
focus on ‘your own health state today’. 
 
General population value sets vs patient population value sets 
If you want to undertake a utility analysis you will need to use a value set. Generally 
speaking utility analysis requires a general population-based value set (as opposed 
to a patient-based set). The rationale behind this is that the values are supposed to 
reflect the preferences of local taxpayers and potential receivers of healthcare. 
Additionally, patients tend to rate their health states higher than the general 
population because of coping etc, often underestimating their need for healthcare. 
The EQ-5D value sets are therefore based on the values of the general population.  
 
Difference between the EQ-5D descriptive system and the EQ VAS 
The descriptive system can be represented as a health state, e.g. health state 11212 
represents a patient who indicates some problems on the usual activities and 
anxiety/depression dimensions. These health states can be converted to a single 
index value using (one of) the available EQ-5D value sets. These value sets have 
been derived using VAS or TTO valuation techniques, and reflect the opinion of the 
general population. The EQ VAS scores are patient-based and are therefore not 
representative of the general population. The EQ VAS self-rating records the 
respondent’s own assessment of their health status. The EQ VAS scores however 
are anchored on 100 = best imaginable health and 0 = worst imaginable health, 
whereas the value sets are anchored on 11111 = 1 and dead = 0 and can therefore 
be used in QALY calculations. 
 
 
 
 
19 
 

 
Difference between the VAS and TTO techniques 
The difference between the value sets based on TTO and those based on VAS is 
that the techniques used for the elicitation of the values on which the models are 
based differ. In the  TTO task, respondents are asked, for example, to imagine they 
live in a health state (e.g. 22222) for 10 years and then asked to specify the amount 
of time they are willing to give up to live in full health instead (i.e. 11111). For 
example, someone might find 8 years in 11111 equivalent to 10 years in 22222. The 
VAS technique on the other hand, asks people to indicate where, on a vertical 
thermometer-like scale ranging from best imaginable health to worst imaginable 
health, they think a health state should be positioned.  
 
Multinational clinical trials 
Information relating to EQ-5D health states gathered in the context of multinational 
trials may be converted into a single summary index using one of the available EQ-
5D value sets. There are different options available to do this using appropriate value 
sets-however the choice depends on the context in which the information will be used 
by researchers or decision makers. In cases where data from an international trial 
are to be used to inform decision makers in a specific country, it seems reasonable to 
expect  decision makers to be interested primarily in value sets that reflect the values 
for EQ-5D health states in that specific country. So for example, if applications for 
reimbursement of a drug are rolled out from country to country, country-specific value 
sets should be applied and reported in each pharmaco-economic report. This is no 
different from the requirement to use country-specific costs. In the absence of a 
country-specific value set, the researcher should select another set of values for a 
population that most closely approximates that country.  Sometimes however, 
information about utilities is required to inform researchers or decision makers in an 
international context. In these instances, 1 value set applied over all EQ-5D health 
states data is probably more appropriate.  
 
The decision about which value set to use will also depend on whether the relevant 
decision making body in each country specifies any requirements or preferences in 
regard to the methodology used in different contexts (e.g. TTO, standard gamble 
(SG), VAS or discrete choice modelling (DCM)). These guidelines are the topic of an 
international ongoing debate but the EuroQoL website is planning to provide a 
summary of health care decision-making bodies internationally, and their stated 
requirements regarding the valuation of health states.  
 
 
 
20 
 

 
Detailed information regarding the valuation protocols, guidelines on which value set 
to use and tables of all available value sets has recently been published by Springer 
in: EuroQoL Group Monograph series: Volume 2: EQ-5D value sets: inventory, 
comparative review and user guide’ (see section 8 for more information). Chapter 4 
by Nancy Devlin and David Parkin will be of special interest to researchers pondering 
the issue of which value set to use.  
 
 
21 
 

 
8. Additional information 
Key EuroQol references 
1. The EuroQol Group (1990). EuroQol-a new facility for the measurement of 
health-related quality of life. Health Policy 16(3):199-208.  
 
2. Brooks R (1996). EuroQol: the current state of play. Health Policy 37(1):53-72. 
 
3. Dolan P (1997). Modeling valuations for EuroQol health states. Med Care 
35(11):1095-108. 
 
4. Roset M, Badia X, Mayo NE (1999). Sample size calculations in studies using the 
EuroQol 5D. Qual Life Res 8(6):539-49.    
 
5. Greiner W, Weijnen T, Nieuwenhuizen M, et al. (2003). A single European 
currency for EQ-5D health states. Results from a six country study. Eur J Health 
Econ; 4(3):222-231. 
 
6. Shaw JW, Johnson JA, Coons SJ (2005). US valuation of the EQ-5D health 
states: development and testing of the D1 valuation model. Med Care; 43(3): 
203-220. 
 
Referring to the EQ-5D instrument in publications 
When publishing results obtained with the EQ-5D, the following references can be 
used: 
1. The EuroQol Group (1990). EuroQol-a new facility for the measurement of 
health-related quality of life. Health Policy 16(3):199-208.  
 
2. Brooks R (1996). EuroQol: the current state of play. Health Policy 37(1):53-72. 
 
If you used a value set in your study you can also include a reference to the 
publication regarding that value set. The appropriate references for the value sets 
can be found in the EQ-5D Value Sets Monograph and in the value set summary 
documents that can be ordered from the EuroQoL Executive Office. 
 
Products available from the EuroQoL Executive Office 
EQ-5D language versions/guidelines for different modes of administration 
All language versions and guidelines for different modes of administration must be 
obtained exclusively from the EuroQoL Executive Office. Normally only the 
language(s) appropriate to the country where the research request originates will be 
supplied. They are distributed freely provided the research is not being funded by a 
commercial organization (e.g. a pharmaceutical or medical device company). In 
these latter instances, sponsorship is requested. 
 
 
 
22 
 

 
The Measurement and valuation of health status using EQ-5D: A European 
perspective. Eds Brooks R, Rabin R, de Charro F. Kluwer Acacemic Publishers, 
2005 
This book reports on the results of the European Union-funded EQ-net project which 
furthered the development of EQ-5D in the key areas of valuation, application and 
translation. The book can be obtained from Springer at www.springeronline.com at a 
cost of €107.95.  
 
Measuring self-reported population health: An international perspective based 
on EQ-5D. Eds Szende A, Williams A. EuroQoL Group Monographs Volume 1. 
SpringMed publishing, 2004. 
This booklet provides population reference data for a number of different countries 
and is available on request from the EuroQoL Executive Office. 
 
EQ-5D concepts and methods: a developmental history. Eds Kind P, Brooks R, 
Rabin R. Springer, 2005. 
This book is a collection of papers representing the collective intellectual enterprise 
of 
the 
EuroQoL 
Group 
and 
can 
be 
obtained 
from 
Springer 
at 
www.springeronline.com at a cost of € 85.00. 
 
EQ-5D value sets: Inventory, comparative review and user guide. Eds. Szende 
A, Oppe M, Devlin N. EuroQoL Group Monographs Volume 2. Springer, 2006.  
This book provides an essential guide to the use of the EuroQoL Group’s value sets 
for anyone working with EQ-5D data and can be obtained from Springer at 
www.springeronline.com at a cost of € 49.95. 
 
Future developments 
Since 2002, the EuroQoL Foundation has provided modest funding for EuroQoL 
members to carry out innovative EQ-5D-related research. Since 2004, the Group has 
been establishing specific task forces to: 
 
• 
Investigate the use of EQ-5D in different disease areas 
• 
Develop a 5-level version of EQ-5D  
• 
Explore different valuation methodologies for the 5-level version 
• 
Develop an EQ-5D version for children aged 7-12 years in different languages 
• 
Investigate the use of EQ-5D in population health 
 
 
23 
 

 
• 
Explore the use of electronic versions of EQ-5D in pc and web-based 
applications as well as palm pilots and (in the future) cell phones. This task 
force will also investigate the eliciting of values via the computer  
 
Contact information: 
For more information please look at the EuroQoL website at www.euroqol.org or e-
mail us at userinformationservice@euroqol.org
 
Acknowledgements: 
Part of this user guide was taken from and is based on the UK user guide that was 
developed by Professor Paul Kind from York University, UK in 1998. 
 
 
24 
 

 
Study Number 2006‐05
Carpentier‐Edwards PERIMOUNT Magna Mitral Valve 
EQ‐5D
Quality of Life Survey
Page 1 of 2
 
 
 
Patient ID # 
2  0  0  6  0  5 
 
 
 
       Patient Initials (First, Last) 
 
 
 
 
 
The EuroQol Group (1990). EuroQol‐a new facility for the measurement of health‐related quality of life. Health Policy 16(3):199‐208. 
PROPRIETARY DATA:  This document and information contained herein may not be reproduced, used, or disclosed without written permission of Edwards Lifesciences,
 
Heart Valve Therapy Group, Clinical Affairs 
 
 
By placing a checkmark in one box in each group below, please indicate which 
statements best describe your own health state today. 
 
Mobility 
I have no problems in walking about 
 
 
I have some problems in walking about 
 
 
I am confined to bed 
 
 
 
Self‐Care 
I have no problems with self‐care 
 
 
I have some problems washing or dressing myself 
 
 
I am unable to wash or dress myself 
 
 
 
Usual Activities (e.g. work, study, housework, family or leisure activities) 
I have no problems with performing my usual activities 
 
 
I have some problems with performing my usual activities 
 
 
I am unable to perform my usual activities 
 
 
 
Pain/Discomfort 
I have no pain or discomfort 
 
 
I have moderate pain or discomfort 
 
 
I have extreme pain or discomfort 
 
 
 
Anxiety/Depression 
I am not anxious or depressed 
 
 
I am moderately anxious or depressed 
 
 
I am extremely anxious or depressed 
 
 

 
Study Number 2006-05 
Carpentier-Edwards PERIMOUNT Magna Mitral Valve 
EQ-5D 
Quality of Life Survey 
 
Page 2 of 2
 
Patient Study ID #  
2 
0 
0 
6 
0 
5 
 
 
 
 
Patient Initials (First, Last)  
 
 
 
 
 
 
 
 
 
The EuroQol Group (1990). EuroQol‐a new facility for the measurement of health‐related quality of life. Health Policy 16(3):199‐208. 
PROPRIETARY DATA:  This document and information contained herein may not be reproduced, used, or disclosed without written permission of Edwards Lifesciences,
 
Heart Valve Therapy Group, Clinical Affairs
 
2
 
 
 
 
To help people say how good or bad a health state is, 
we have drawn a scale (rather like a thermometer) on 
which the best state you can imagine is marked 100 and 
the worst state you can imagine is marked 0. 
 
We would like you to indicate on this scale how good 
or  bad  your  own  health  is  today,  in  your  opinion. 
Please do this by drawing a line from the box below to 
whichever  point  on  the  scale  indicates  how  good  or 
bad your health state is today. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
Your own 
health state 
today 
9 
0
8 
0
7 
0
6 
0
5 
0
4 
0
3 
0
2 
0
1 
0
100
Worst 
imaginable 
health state 
0 
Best  
imaginable 
health state 

Magna Mitral Post Approval Study Protocol 2006-05   
 
 REV I  November 18, 2013  
 
 
 
 
 
 This document and the information contained herein is considered Proprietary and Confidential  
and may not be reproduced, used or disclosed without written permission from Edwards Lifesciences LLC. 
 
 
- pg 79 of 80 - 
 
19.0  APPENDIX 8:  ADVERSE EVENT DEFINITIONS 
 
 
 

Adverse Event Definitions
Page 1 of 13
Confidential
Primary 
Event Name
Subcategory 
General Definition
Device or Procedure 
Relationship
Bleeding Events
Bleed-Hemorrhage
ISO 14155-1, Section 3.1 Adverse 
Device Effect (ADE) any untoward 
or unintended response to a 
medical device.                                  
ISO 14155-1, 3.18: Serious 
Adverse Device Effect (SADE) 
Adverse device effect that has 
resulted in any of the 
consequences characteristic of a 
serious adverse event or that might 
have led to any of these 
consequences if suitable action had 
not been taken or intervention had 
not been made or if circumstances 
had been less opportune.
Anticoagulant-
related Bleed 
(hemorrhage)
Any episode of major internal or external bleeding related to the use of 
anticoagulation that causes death, hosptalization, or permanent injury (e.g., vision 
loss) or necessitates transfusion.
Not defined
Bleeding 
Diatheses 
related to AC
Bleeding diathesis is an unusual susceptibility to bleeding mostly due to a 
coagulopathy.
Coagulopathy
Development of a new bleeding disorder (one that was not diagnosed prior to the 
index procedure),  documented by laboratory studies. 
Event is procedure related if it 
occurs within 30 days of the date of 
the index procedure.  
DIC
Systemic /widespread formation of thromboses in the microcirculation, mainly within 
the capillaries.  Secondary complication of a wide variety of coagulation disorders 
which activate the intrinsic coagulation sequence.
Not defined
Heparin Induced 
Thrombocytope
nia (HITS)
HITS is diagnosed when thrombocytopenia (defined as >50% of the baseline value or 
a low platelet count between 20–100 × 10^9/liter) is reported caused by administration 
of various forms of heparin. HITS must be confirmed by a Heparin Assay and or D-
Dimer laboratory test.
Not defined
A bleeding event is any episode of major internal or external bleeding that causes death, hospitalization, or permanent injury (eg, vision loss) or necessitates 
transfusion. Major bleeding unexpectedly associated with minor trauma should be reported as a bleeding event, but bleeding associated with major trauma or 
a major operation is considered secondary to those events and should not be reported. Bleeding events are reported for all patients regardless of whether 
they are taking anticoagulants or antiplatelet drugs. Although total bleeding events must be reported, bleeding events can also be reported separately for 
those who are taking anticoagulants or antiplatelet agents and those who are not.  Bleeding Events are further categorized as below.

Adverse Event Definitions
Page 2 of 13
Confidential
Other 
Coagulopathy
Coagulopathy other than DIC or HITS confirmed by laboratory tests.
Not defined
Hematoma
Collection of blood (or its degradation products) which exceeds 5 cm in diameter, 
requires treatment or prolongs hospitalization.
Not defined
Specify site
Hemolysis
The destruction of red blood cells, caused by disruption of the cell membrane and 
resulting in the release of hemoglobin.  The clinical diagnosis is made by the 
measurement of plasma free hemoglobin.
Not defined
Hemolytic 
Anemia
Anemia due to hemolysis, either in the blood vessels (Intravascular hemolysis) or 
elsewhere in the body (extravascular).
Not defined
Mechanical 
hemolytic 
anemia 
(extravascular)
A form of hemolytic anemia due to mechanically induced damage to red blood cells. 
Red blood cells, while flexible, may in some circumstances succumb to physical shear 
and compression. A common form, called microangiopathic hemolytic anemia , is a 
chronic condition due to prosthetic heart valves.
Not defined
GI Bleed
General Def
Detection or frank blood or hemoglobin in the GI tract documented by diagnostic test 
or laboratory results that causes death, hospitalization, or permanent injury (eg, vision 
loss) or necessitates transfusion. Refer to definition of "Bleeding Events" for 
reportability.
Not defined
Upper
Detection of frank blood or hemoglobin in the upper gastrointestinal tract confirmed by 
diagnostic or laboratory test result.
Not defined
Lower
Detection of frank blood or hemoglobin in the stool documented by hemmocult test or 
other diagnostic procedure. 
Not defined
Intracranial 
Bleed
Includes all bleeding within the cranium either subarachnoid, intra-parenchymal, or 
intracerebral requiring treatment or resulting in neurological deficit.  Bleeding related 
neurological events should be captured as bleeding complications (See Bleeding) 
while embolic related deficits should be recorded as embolic events. 
Not defined
Bleeding Events Pericardial 
Tamponade
Fluid accumulation between the myocardium and pericardium of the heart creating 
hemodynamic compromise. Severity of the tamponade may dictate the degree of 
intervention (invasive or non-invasive, surgical or Pericardiocentesis). This should be 
documented by either:
1. Echo showing pericardial fluid and
signs of tamponade such as right heart
compromise.
2. Systemic hypotension due to
pericardial fluid compromising cardiac function.
Not defined

Adverse Event Definitions
Page 3 of 13
Confidential
Procedural 
Bleeding
Any abnormal blood loss that occurs during the index procedure, in the opinion of the 
investigator.  The volume of blood loss during the procedure shall be recorded on the 
case report form. 
Not defined
Post-
Procedural 
Abnormal bleeding that is related to the index procedure in the opinion of the 
investigator, that occurs after the patient leaves the OR. 
Not defined
Other Bleed, 
specify 
Other bleeding event that does NOT fit in one of the above categories.
Not defined
Cardiac 
Complications
Angina
Angina is due to an inadequate supply of oxygen to the heart muscle. Symptoms may 
include: chest pain, tight or heavy feeling in the chest, or discomfort which spreads 
from the chest to the arm, back, neck, jaw, or stomach, numbness or tingling in the 
shoulders, arms or wrists, shortness of breath, and nausea relieved by rest or 
nitroglycerine. Stable angina has no change in frequency or pattern for 6 weeks. 
Angina which increases in frequency, intensity, or duration, which occurs at rest, or 
which is new in onset is considered unstable angina. Event should be documented 
and confirmed by EKG test results.
Angina -stable
No change in frequency or pattern for 6 weeks.
Not defined
Angina-unstable Chest pain extending over a 6-hour period that does not respond to treatment.
Not defined
Annular 
Dissection
Dissection of the valvular annulus extending into the aorta which may occur due to 
disease state (friable tissue) or may be due to mechanical trauma  such as over sizing 
of balloon expandable product, insertion of prosthetic valve or other valvular 
accessory product placement. Annular dissection occurring within 30 days of the 
index procedure will be considered related.
Event is considered procedure 
related if it occurs within 30 days of 
the index procedure.
Aortic 
Dissection
Disruption of the media layer of the aorta with bleeding within and along the wall of the 
aorta. Dissection may, and often does, occur without an aneurysm
being present. Aortic dissection may occur in the ascending thoracic aorta (Type A 
dissection) or in thr descending thoracic aorta ( Type B dissection). Dissection should 
be confirmed by imaging.  
Not defined
Type A
Dissection occurs in the ascending aorta.
Not defined
Type B
Dissection occurs in the descending aorta.
Not defined
Arrhythmia
General 
definition
A documented arrhythmia when the specific condition did not exist before, or has 
been exacerbated since  the index procedure .  All Arrhythmias should be 
documented and confirmed with EKG test results.
Not defined
Cardiac 
Complications
Atrial Fibrillation Atrial fibrillation is a disorganized, irregular, rapid heart rate. Symptoms may include 
heart palpitations, shortness of breath, weakness and fatigue and may lead to stroke. 
Not defined

Adverse Event Definitions
Page 4 of 13
Confidential
Atrial Flutter
Well organized  but overly rapid contractions of the atrium of the heart (usually at a 
rate of 250-350 contractions per minute).
Not defined
AV Block
A conduction disorder of the nervous impulse at the level of the atrioventricular 
junction, i.e. between the atrium and the ventricle.  
Not defined
AV Block I
A conduction disorder of the nervous impulse at the level of the atrioventricular 
junction, i.e. between the atrium and the ventricle.  
Not defined
AV Block II
A conduction disorder of the nervous impulse at the level of the atrioventricular 
junction, i.e. between the atrium and the ventricle.   
Not defined
AV Block III
A conduction disorder of the cardiac conduction system with complete absence of AV 
conduction. With third degree block, no P waves conduct to the ventricle and AV 
dissociation is complete. 
Bradycardia
An abnormally slow heart rate (typically defined as <60 bpm in adults) and which may 
require implantation of a pacemaker to maintain a normal heart rate.  
Not defined
Bundle Branch 
Block                   
Bundle branch block is an intraventricular conduction defects (IVCD) that disrupts the 
normal flow of electrical impulses that result in a normal heart beat.   A QRS duration 
of greater than 110 milliseconds is a diagnostic indication of BBB.
Not defined
BBB- Left 
Partial
BBB- Left 
Complete
BBB - Right 
partial
BBB- Right 
complete
Superventricular 
Tachycardia 
(SVT)
Sustained tachyarrhythmia in which the QRS appears normal and has a duration of < 
120 msec. 
Not defined
Ventricular 
Fibrillation
A rapid irregular ventricular rhythm due to multiple reentrant activity associated with 
essentially zero cardiac output. VF may be fatal unless treated by defibrillation 
(electric shock). 
Not defined
Ventricular 
Tachycardia
Defined as a regular heart rhythm originating from the ventricle with a frequency of 
160 to 200 beats per minute. 
Not defined
Other 
Arrhythmia, 
specify:
Any other type of arrhythmia not listed above
Not defined

Adverse Event Definitions
Page 5 of 13
Confidential
Cardiac 
Complications
Arterial 
Dissection
Separation of the inner arterial walls due to mechanical dilatation of the artery or 
ablation of atherosclerotic plaque. Associated with plaque fracture, intimal splitting 
and localized medial dissection. Tears may extend into the media for varying 
distances, and may even extend through the adventitia resulting in frank perforation. 
The National Heart, Lung and Blood Institute (NHLBI) classification system for intimal 
tears, (dissections) are graded based upon their angiographic appearances as types 
A through F. In general, type A and B dissections are clinically benign and do not 
adversely affect procedural outcome. However, types C through F are considered 
major dissections and carry a significant increase in morbidity and mortality.
Note: NHBLI definitions refer to both coronary and peripheral vascular dissections - 
see Reference. 
Type A
Minor radiolucent areas within the coronary lumen during contrast injection with little 
or no persistence of contrast after the dye has cleared.
Not defined
Type B
Parallel tracts or a double lumen separated by a radiolucent area during contrast 
injection, with minimal or no persistence after dye clearance. 
Not defined
Type C
Appear as contrast outside the coronary lumen ("extraluminal cap") with persistence 
of contrast after dye has cleared from the lumen
Not defined
Type D
Represent spiral ("barber shop pole") luminal filling defects, frequently with excessive 
contrast staining of the dissected false lumen.
Not defined
Type E
Appear as new, persistent filling defects within the coronary lumen.
Not defined
Type F
Represent those that lead to total occlusion of the coronary lumen without distal 
antegrade flow.
Not defined
Cardiac Arrest
Cardiac arrest documented by one of the following: ventricular fibrillation, rapid 
ventricular tachycardia with hemodynamic instability, asystole.
Not defined
Cardiogenic 
Shock
A clinical state of hypoperfusion sustained for greater than 30 minutes, with either 
systolic blood pressure < 80 mm Hg, and /or Cardiac Index < 1.8 despite maximal 
treatment (fluids) or 2)  requiring intravenous inantropes and/or pressor agent or an 
intraortic balloon pump (IABP). 
Not defined
Heart Failure      
(aka Cardiac 
Failure)
An event is which the heart fails to meet the circulatory requirements of the body 
under differing physiological circumstances, and/or a state in which cardiac output is 
reduced relative to the demands of the body, assuming the evidence of adequate 
venous return. Event is confirmed clinically or by diagnostic testing
Event is considered Valve Related 
if event is new event which is not 
continued from preoperative heart 
failure, is caused by one of the 
following prosthesis related events: 
AC related hemorrhage, 
endocarditis, non-structural 
dysfunction, perivalvular leak, 
structural deterioration, 
thromboembolism, thrombosis, re-
op or unknown causes.  

Adverse Event Definitions
Page 6 of 13
Confidential
Cardiac 
Complications
Hypotension
Abnormally low blood pressure. For an adult, hypotension is defined as blood 
pressure less than 90/50 mmHg.  Because arterial pressure is determined by cardiac 
output, venous pressure and systemic vascular resistance a reduction in either one or 
all of these variables can lead to hypotension.
Not defined
Hypertension
Defined as blood pressure > 140 /90 mm Hg for patient without diabetes or kidney 
disease,  >130/80 mmHg for patients on 2 occasions with diabetes or renal disease.
Not defined
Pericardial 
Effusion
Excess fluid accumulation in the pericardium that interferes with normal heart 
function.  May be related to inflammation of the pericardium due to disease or injury, 
but can result from the accumulation of blood after a surgical procedure or injury.   
Diagnosis of pericardial effusion should be confirmed by echocardiography or CT and 
reported when it requires medication or medical intervention to resolve.
Not defined
Perforation of 
the free 
myocardial 
An abnormal hole or opening in the heart wall caused by a device causing puncture 
through the wall or by pressure against a weakened portion of the wall.
Not defined
Myocardial 
Infarction 
Peri-operative Myocardial Infarction (MI) (0-24 hours post-op) as documented by the 
following criteria: The CK-MB (or CK if MB not available) must be ≥5 times the upper 
limit of normal, with or without new Q waves present in two or more contiguous ECG 
leads. No symptoms required. Peri-operative  Myocardial Infarction (MI) (> 24 hours 
post-op) as documented by at least one of the following criteria:1. Evolutionary ST- 
segment elevations, 2. Development of new Q- waves in two or more contiguous ECG 
leads, 3. New or presumably new LBBB pattern on the ECG, CK4. The CK-MB (or CK 
if MB not available) must be greater than or equal to 3 times the upper limit of Normal.
Not defined
Embolic 
Events
Embolism 
General Def
An embolism is a free flowing blood clot or lesion material that is located in the 
systemic or pulmonary circulation that occurs in the absence of infection after 
immediate perioperative period.  May be manifested as neurological event or non-
cerebral embolic event.  Non-cerebral event is an embolus documented operatively, 
autopsy or clinically that produces signs and symptoms attributable to partial or 
complete obstruction of a peripheral artery. Excludes post-operative MI unless 
detected by operation, clinical imaging or autopsy, emboli caused by non-thrombotic 
material (atherosclerosis, myxoma).
Not defined
Thromboembol
ism
The combination of thrombosis and its main complication, embolism.  Thrombosis is 
the formation of a blood clot inside a blood vessel, obstructing the flow of blood 
through the circulartory system
Not defined

Adverse Event Definitions
Page 8 of 13
Confidential
Pneumonia
Lung infection documented by blood studies or chest x-ray, requiring treatment with 
antibiotics, inhalation therapy, intubation or suctioning.  
Event will be considered procedure 
related when occurs within 30 days 
of the index procedure.  
Sepsis/Septice
mia
Sepsis (also known as septicemia).  Positive blood and clinical evidence of infection ( 
e.g. fever, elevated WBC count, hypotension, end organ dysfunction)  Event must be 
confirmed by 2 consecutive positive blood cultures, explant or autopsy. 
Not defined
Infection local: Sternal Wound 
Infection
Deep sternal infection involving muscle, bone, and/or mediastinum. Must include one 
of the following: 1) wound opened with excision of tissue (I&D); 2) positive culture; 3) 
treatment with antibiotics. Infection that is contiguous with the sternum on imaging will 
constitute involvement of the sternum. 
Event will be considered procedure 
related when occurs within 30 days 
of the index procedure.  
Infection local, 
specify site:
Other localized infection that is NOT related to the sternal access.
Infection, 
systemic: 
specify
Other systemic infection that is not already identified in another category.
Infection, 
other: specify
Any other infection that cannot be determined to be local or systemic
Pulmonary
Atelectasis
Complete or partial collapse of a previously inflated lung, inability of lung to fully 
expand.
Pleural Effusion
Excess accumulation of blood or other fluids in the pleura, which is common after 
cardiac surgery. Reportable when it becomes symptomatic and diagnosis is confirmed 
by appropriate imaging.  
Pneumothorax
Abnormal presence of air in the pleural cavity. Accumulation of air or gas in the 
pleural cavity, occurring as a result of disease or injury and requiring medication or 
medical intervetion to resolve. 
Pulmonary 
Edema
An abnormal accumulation of fluid in the lungs requiring medication or medical 
intervention to resolve.
Pulmonary 
Embolism (PE)
See Embolism-PE.
Pulmonary
Pulmonary 
Hypertension
Mean pulmonary artery pressure that is greater than 25 mmHg at rest and/or greater 
than 30 mmHg during exercise confirmed by SG catheter or diagnostic placement in 
the pulmonary artery bed and condition requires medication or medication intervention 
to resolve or treat the condition.

Adverse Event Definitions
Page 9 of 13
Confidential
Respiratory 
Dysfunction/In
sufficiency
Deterioration of patient’s respiratory efforts less than 24 hrs after completion of the 
index procedure.
Respiratory failure reported within 
30 days of the index procedure is 
considered procedure related. 
Respiratory failure reported later 
than 30 days arter the index 
procedure will be recorded as an 
AE or SAE, but will not be 
considered procedure related.
Respiratory 
Failure
Need for mechanical ventilation required greater than 24 hrs after of completion of the 
index procedure, or need for reintubation and ventilator support occurring any time 
within 30 day of the index procedure will be considered related to the index procedure. 
Event occurring any time within 30 
day of the index procedure will be 
considered procedure related.
Other 
Respiratory, 
specify
Other respiratory event that is NOT respiratory failure. 
Event will be considered procedure 
related when occurs within 30 days 
of the index procedure.  
Renal
Renal 
Dysfunction
An acute event or worsening of renal function post-operatively (Increase of serum 
creatinine to < 2.0, and < 2x most recent preoperative creatinine level) and does NOT 
require dialysis.
Not defined
Renal Failure
An acute event or worsening of renal function resulting in one or more of the following: 
1)   Increase of serum creatinine to >2.0, and 2x most recent preoperative creatinine 
level. 2) A new requirement for dialysis postoperatively.
Not defined
Other Renal, 
specify
Other event that is not renal failure or renal dysfunction
    
Vascular
Vascular 
Access Site 
Complication
Report under Bleeding or Infection.
Deep Vein 
Thrombosis 
(DVT)
Formation of blood clot (thrombus) in the lower extremities (legs) characterized by 
swelling, redness, claudication/pain in affected limb. Event should be confirmed by 
Doppler or Duplex US study, and require medication or medical intervention to 
resolve. 
Not defined
Other Vascular, 
specify
Other vascular complications that are not captured in any other AE definition.
Not defined
Valvular

Adverse Event Definitions
Page 10 of 13
Confidential
Aortic Stenosis
Obstruction of flow at the aortic valve due to restricted leaflet opening, with a mean 
transvalvular pressure gradient of at least 10 mm Hg. Does not including the 
subvalvular and supravalvular forms of this disease. The cause of the stenosis can be 
further defined based on the anatomy and disease process affecting the valve.
Mild 
 Jet velocity (m/s) <3.0; Mean Gradient (mmHg) <25; Valve Area (cm2) < 1.5.
Moderate
 Jet velocity (m/s) 3.0-4.0; Mean Gradient (mmHg) 25-40; Valve Area (cm2) 1.0- 1.5.
Severe
 Jet velocity (m/s) >4.0; Mean Gradient (mmHg) >40; Valve Area (cm2) <1.0; Valve Area Index<0.6.
Aortic 
Regurgitation
Incompetence of the aortic valve, in which a portion of the left ventricular forward 
stroke volume returns to the chamber during diastole. The cause of the regurgitation, 
is further defined based on the anatomy of the valve and aortic root and the disease 
process affecting the valve.
Valvular
Mild
Qualitative: Angiographic grade 1+; Color Doppler jet Width-Central jet, width less 
than 25% of LVOT. Doppler Vena Contracta Width (cm) <0.3. Quantitative (by Echo 
or Angio):Regurgitant volume (ml/beat) <30; Regurgitant fraction (%) <30;Regurgitant 
orifice area (cm2) < 0.10.
Moderate
Qualitative: Angiographic grade- 2+; Color Doppler jet Width- Central jet, greater than 
Mild but no signs of Sever AR. Doppler Vena Contracta Width (cm) 0.3-0.6. 
Quantitative (by Echo or Angio):Regurgitant volume (ml/beat) 30-59; Regurgitant 
fraction (%) 30-49;Regurgitant orifice area (cm2) 0.10-0.29.
Severe
Qualitative: Angiographic grade- 3-4+; Color Doppler jet Width- Central jet, width > 
65% of LVOT. Doppler Vena Contracta Width (cm) >0.6. Quantitative (by Echo or 
Angio):Regurgitant volume (ml/beat) >60; Regurgitant fraction (%) >50;Regurgitant 
orifice area (cm2) >0.3.
Mitral Stenosis
Mitral stenosis (MS) refers to narrowing of the mitral valve orifice, resulting in 
impedance of filling of the left ventricle in diastole. It is usually caused by rheumatic 
heart disease. Less common causes include severe calcification of the mitral annulus, 
infective endocarditis, systemic lupus erythematosus, rheumatoid arthritis, and 
carcinoid heart disease. The severity of MS is defined by the mitral valve area (MVA) 
where normal valve area is 4 to 5 cm2. 
Mild
Mean gradient (mm Hg) < 5; Pulmonary artery systolic Pressure  (mm Hg)< 30; Valve 
Area (cm2) >1.5.
Moderate
Mean gradient (mm Hg) 5-10; Pulmonary artery systolic Pressure  (mm Hg) 30-50; 
Valve Area (cm2) 1.0-1.5.
Severe
Mean gradient (mm Hg) > 10; Pulmonary artery systolic Pressure  (mm Hg)> 50; 
Valve Area (cm2)<1.0.
Mitral 
Regurgitation
Also known as mitral incompetence and mitral insufficiency is leakage of blood 
backward through the mitral valve each time the left ventricle contracts. Diagnosed by 
auscultation (murmur) or echocardiography.

Adverse Event Definitions
Page 11 of 13
Confidential
Mild
Qualitative: angiographic grade 1+; Color Doppler jet area- Small, central jet (<4 cm2 
or<20% LA area); Doppler vena contracta width (cm) < 0.3. Quantitative (cath or 
echo):Regurgitant volume (ml/beat) <30;Regurgitant fraction (%) <30; Regurgitant 
orifice area (cm2) <0.20.
Moderate
Qualitative: angiographic grade 2+; Color Doppler jet area- signs of MR greater than 
Mild present but no criteria for Sever Mr; Doppler vena contracta width (cm) 0.3-69. 
Quantitative (cath or echo):Regurgitant volume (ml/beat) 30-59;Regurgitant fraction 
(%) 30-49; Regurgitant orifice area (cm2) 0.20-0.39.
Severe
Qualitative: angiographic grade3-4+; Color Doppler jet area- Vena contracta width > 
0.7 with large central MR jet (area > 40% of LA area) or with a wall-impinging jetof any 
size, swirling in LA; Doppler Vena contracta width > 0.7. Quantitative (cath or 
echo):Regurgitant volume (ml/beat) >/=60;Regurgitant fraction (%) >/=50; Regurgitant 
orifice area (cm2) >/=0.40.
Tricuspid 
Stenosis
A narrowing of the tricuspid valve opening that increases resistance to blood flow from 
the right atrium to the right ventricle. Severe tricuspid stenosis is defined as a valve 
area less than 1.0 cm2.
Tricuspid 
Regurgitation
Insufficiency of the tricuspid valve causing blood flow from the right ventricle to the 
right atrium during systole. Severe regurgitation characterized by Vena contracta 
width greater than 0.7 cm and Systolic flow reversal in hepatic veins.
Other Valve, 
specify 
location:
Other valve (e.g. pulmonic) valve disease or deterioration reported after the AVR 
procedure.
Structural 
Deterioration
Includes dysfunction or deterioration involving the replacement heart valve (exclusive 
of infection or thrombosis) determined by reoperation, autopsy or clinical investigation. 
Refers to changes intrinsic to the valve such as wear, fracture, leaflet escape, 
calcification, leaflet tear, stent creep, suture line disruption of components of 
prosthetic valve, new chordal rupture, leaflet disruption, or leaflet retraction of repaired 
valve. 
By definition all are valve related.
Calcification
Leaflet tear
Stress Fracture
Stent creep
Suture line 
disruption
Wear damage
Loss of 
structural 
integrity 
Loss of structural integrity of metallic valve component such as wireform, frame, etc.

Adverse Event Definitions
Page 12 of 13
Confidential
Other Structural 
Deterioration, 
specify:
Valvular
Non Structural 
Dysfunction
Any abnormality not intrinsic to the valve itself that results in stenosis or regurgitation 
of the replacement heart valve. Refers to problems (exclusive of thrombosis and 
infection) that do not directly involve valve components yet result in dysfunction as 
diagnosed by reoperation, autopsy or clinical investigation.  E.g. Entrapment by 
pannus, tissue or suture, PV leak, inappropriate sizing or positioning, residual leak or 
obstruction after valve implantation or repair, regurgitation due to technical errors, 
dilatation of the sinotubular junction, dilatation of the valve annulus.  In AVR 
percutaneous approaches: new onset of coronary ischemia from ostial obstruction or 
PV aortic regurgitation.  
Annulus 
dilatation
Entrapment-
leaflet
Specify leaflet
Entrapment-
pannus
Inappropriate 
Sizing
Inappropriate 
Positioning
Ostial 
obstruction
Perivalvular 
Leak
Clinically or haemodynamically detectable defect between the heart valve substitute 
and the patient's annulus. 
Major 1. PAL requiring surgical re intervention, and;                             2. PVL requiring 
medical intervention only (i.e., after load reduction, occasional blood transfusion for 
mild Hemolysis).
Minor 1. Evidence of AI by echo without symptoms and with no Hemolysis that does not 
require any intervention.
2. Presence of non-laminar flow without symptoms and with no hemolysis that does 
not require any intervention and requires monitoring.
Valve 
Thrombosis
Blood clot, not associated with infection, causing dysfunction of the heart valve 
substitute. Diagnosis confirmed by echocardiography, angiocardiography or magnetic 
resonance imaging, operation, explant, or autopsy.

Adverse Event Definitions
Page 13 of 13
Confidential
Other Non 
Structural 
Dysfunction, 
specify
Other structural dysfunction not defined above.
Other Events
Allergic 
Reaction
Hypersensitivity to an allergen such as a medication, contrast agent, food or airborne 
substance.  The reaction can be characterized by rash, nausea, vomiting, upper 
respiratory congestion, urticaria, shortness-of-breath, vasovagal reaction, or general 
collapse (anaphylaxis) Specific Allergen should be reported if known. 
Not defined
Esophageal 
Injury
Any evidence of puncture/dissection/perforation, varices or other damage to the 
esophagus requiring intervention..
Not defined

Magna Mitral Post Approval Study Protocol 2006-05   
 
 REV I  November 18, 2013  
 
 
 
 
 
 This document and the information contained herein is considered Proprietary and Confidential  
and may not be reproduced, used or disclosed without written permission from Edwards Lifesciences LLC. 
 
 
- pg 80 of 80 - 
20.0  APPENDIX 9:  CLINICAL RISK ASSESSMENT  
 

 
 
Table of Contents 
 
1 
INTRODUCTION ................................................................................................... 3 
1.1 
Device Description .................................................................................... 3 
1.2 
Intended Use ............................................................................................ 5 
1.2.1 
Indications ......................................................................................... 5 
1.2.2 
Contraindications .............................................................................. 6 
1.3 
Proposed Benefit ...................................................................................... 6 
1.4 
Risks, Side Effects, and Adverse Effects ..................................................... 6 
1.5 
Assessment of Clinical Safety and Performance ......................................... 8 
1.5.1 
State of the Art .................................................................................. 8 
1.5.2 
Bench tests ....................................................................................... 10 
1.5.3 
Clinical Data ..................................................................................... 10 
1.5.4 
Literature Review ............................................................................ 16 
1.5.5 
Marketing History ........................................................................... 24 
1.5.6 
Post Market Surveillance ................................................................ 25 
2 
DISCUSSION AND SUMMARY ............................................................................. 30 
3 
REFERENCES ...................................................................................................... 31 
 
 
 
Appendix 9: Page 2 of 32

1 
Introduction 
 
Manufacturer: 
Edwards Lifesciences 
 
 
 
Irvine, California, USA 
 
Medical Device: 
 
Carpentier-Edwards® PERIMOUNT® Plus, Models 6900P / 6900PTFX  
Carpentier-Edwards® PERIMOUNT® Magna Mitral Bioprosthesis Model 7000TFX  
Carpentier-Edwards® PERIMOUNT® Magna Mitral Ease™ Bioprosthesis Model 7200TFX  
Carpentier-Edwards® PERIMOUNT® Magna Mitral Ease™ Bioprosthesis Models 7300 /  
7300TFX  
 
 
Documents taken into Consideration: 
Product Description 
Risk Analysis per BS EN ISO14971:2009 
Instructions for use 
Scientific literature 
Complaint Report Period:  January 01, 2004 to March 31, 2010 
 
 
1.1 
Device Description  
 
The Carpentier-Edwards PERIMOUNT Magna Mitral Ease pericardial bioprosthesis is 
built upon the same proven1
 
 wireform frame and leaflet attachment as the PERIMOUNT 
mitral pericardial bioprostheses models 6900, 6900P, 6900PTFX, 7000TFX, and 7200TFX. 
They are available in sizes 25 – 33 mm (model 7200TFX is available in sizes 27 – 35). The 
bioprosthesis incorporates a sewing ring specifically designed for the mitral position and 
is the first bioengineered mitral bioprosthesis design with three selected bovine 
pericardial leaflets mounted on a flexible metal alloy frame.  
Bovine pericardium was selected for its superior intrinsic properties for valve 
manufacture, notably in terms of collagen content 2 and tolerance to high bending 
curvatures3
1 Marchand MA., et al. Fifteen-year Experience with the Mitral Carpentier-Edwards PERIMOUNT Pericardial 
Bioprosthesis. Ann Thorac Surg. 2001; 71:S236-9. 
. Bovine pericardium tissue is cross-linked using the Neutralogic fixation 
process in which the tissue is placed in a stress-free bath of buffered glutaraldehyde 
solution. The bioprosthesis is treated according to the ThermaFix process, which 
involves heat treatment of the tissue in glutaraldehyde and uses ethanol and 
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. 
Appendix 9: Page 3 of 32

Polysorbate-80 (a surfactant). Glutaraldehyde is shown to both reduce the antigenicity 
of tissue xenograft valves and increase tissue stability.4,5
 
 Glutaraldehyde alone has not 
been shown to affect or reduce the calcification rate of the valve. 
Tissue thickness is measured for each valve size and leaflets are precisely die-cut in 
selected areas of a pericardial sheet. Leaflet deflection testing characterizes each leaflet 
for elasticity. Three leaflets matched for similar thickness and elasticity are then 
assembled. Leaflets are mounted underneath the wireform frame to minimize 
commissural stress points.  
 
The lightweight wireform frame is made of a corrosion-resistant cobalt-chromium alloy, 
chosen because of its superior spring efficiency and fatigue resistance characteristics. 
The frame is designed to be compliant at the orifice as well as at the commissures. The 
frame is covered with a woven polyester fabric sewn with polytetrafluoroethylene 
thread. The wireform frame of the Magna Mitral Ease bioprosthesis is symmetrical and 
the three commissure supports (struts) are equally spaced.  
 
A cobalt-chromium alloy band attached to a polyester film band surrounds the base of 
the wireform frame providing structural support for the orifice and allows for 
radiological identification. In addition to maintaining the orifice shape during 
implantation, the band serves as a point of attachment for the sewing ring. 
 
The sewing ring is made of waffled silicone-rubber and is covered with a porous 
polytetrafluoroethylene cloth sewn with polytetrafluoroethylene thread. The cloth 
facilitates tissue in-growth and encapsulation. The sewing ring of the Magna Mitral Ease 
bioprosthesis is uniquely scalloped along its anterior portion and mimics the natural 
saddle shape of the native mitral valve anatomy. 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 of models 7300 / 7300TFX . Placing sutures through the sewing 
ring and in the region from the suture guide line to the outer portion of the sewing ring 
complements the design of the silicone waffle by easing needle penetration and 
providing variable compliance. The waffle has wider cells along the posterior portion, 
where calcifications or irregularities of the native mitral annulus are more frequent.6
 
  
This results in a very compliant sewing ring that facilitates coaptation between the 
sewing ring and the mitral tissue bed. The width of the sewing ring allows for coverage 
of an irregular or calcified mitral annulus.  
The Tricentrix holder system is designed to minimize the potential for suture or 
chordate entrapment, ease insertion and increase leaflet visibility. The holder consists of 
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. 
Appendix 9: Page 4 of 32

three main components: a grey holder, a white holder post, and a blue adapter. It is 
secured to the bioprosthesis with green sutures. The bioprosthesis and holder 
attachment are suspended by a clip and a sleeve within a sealed jar that contains a 
glutaraldehyde packing solution. The bioprosthesis is terminally sterilized in 
glutaraldehyde. 
 
The design of the model 7200TFX valve is identical to the model 7000TFX valve.  The 
differences between the two valves are that the model 7200TFX has a grey Tricentrix 
holder instead of white, and the sizing conventions of the valves.  The model 7000TFX 
valve is available in sizes 25, 27, 29, 31, and 33 mm.  This sizing is based on the wireform 
diameter. The model 7200TFX sizing is similar to the tissue annulus diameter of the 
valve and is available in sizes 27, 29, 31, 33, and 35.  There are no units associated with 
these sizes because the sizes do not reflect the actual tissue annulus diameter.   
 
The design of the model 7300TFX valve is identical to the model 7000TFX valve.  The 
differences between the two valves are that the model 7300TFX has a Tricolor Tricentrix 
holder system to provide additional contrast (blue instead of white adapter, and white 
instead of grey post) and a black silk suture guide line circles the inflow side of the 
sewing ring.  Modifications were also made to the clip, sleeve, and jar  which are 
packaging components, for user convenience. Modifications were made to the 
accessories which include two sizer types, the barrel and the replica sizers, and a change 
to the handle threads to make it compatible with the Tricentrix Holder, make it longer 
and change in grip color. The only difference between the model 7000 and 7300TFX is 
that, as with other PERIMOUNT models, the TFX version is manufactured with 
pericardial leaflets treated with ThermaFix. 
 
1.2 
Intended Use 
 
Pericardial valves are intended for use in patients suffering from valvular heart disease.  
Models 6900P, 6900PTFX, 7000TFX, 7200TFX, 7300 and 7300TFX are intended for use in 
patients whose mitral valvular disease is sufficiently advanced to warrant replacement 
of their natural valve with a prosthetic one and when the valve cannot be repaired. It is 
also intended for use in patients with a previously implanted mitral valve prosthesis that 
is no longer functioning adequately and requires replacement. 
 
 
1.2.1 Indications 
 
Mitral valvular heart disease is a condition involving any of the following: obstruction of 
the mitral heart valve or stenosis; leakage of the mitral valve, known as regurgitation, 
incompetence, or insufficiency; and combinations of the two, sometimes referred to as 
mixed disease or combined lesions.  Mitral valvular heart disease may be caused by any 
number of factors, including congenital abnormalities, infection by various 
Appendix 9: Page 5 of 32

microorganisms, degenerative calcification, and rheumatic heart disease.  Pericardial 
valves are used particularly in those patients for whom long-term anticoagulation is 
contraindicated or who may be difficult to maintain on anticoagulation therapy.  
 
1.2.2 Contraindications 
 
The contraindications of pericardial valves are determined by the surgeon as those that 
would be contrary to the best interests of the patient.  The decision for or against the 
use of pericardial valves remain with the surgeon who can evaluate all the various risks 
involved, including the anatomy and pathology observed at the time of surgery. 
 
In the presence of conditions affecting calcium metabolism or when calcium containing 
chronic drug therapies are used, the use of a mechanical prosthesis as an alternative 
should be considered. This is also true in patients under 20 years of age, in patients on a 
high calcium diet, and in patients who are on maintenance hemodialysis. 
 
 
1.3 
Proposed Benefit 
 
The patients for whom pericardial valves are intended are those seriously or critically ill 
patients whose prognosis without surgery for replacement of the diseased natural or 
prosthetic valve is unacceptably poor in terms of survival, quality of life, or both in the 
opinion of the attending physicians.   
 
 
1.4 
Risks, Side Effects, and Adverse Effects 
 
As with all prosthetic heart valves, serious complications, sometimes leading to death, 
may be associated with the use of tissue valves. In addition, complications due to 
individual patient 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. 
 
Events associated with the use of stented bioprosthetic heart valves include: 
– Stenosis 
– Regurgitation through an incompetent valve 
– Perivavlular leak 
– Endocarditis 
– Hemolysis 
– Thromboembolism 
– Thrombotic obstruction 
– Bleeding diatheses related to the use of anticoagulant therapy 
Appendix 9: Page 6 of 32

– Malfunctions of the valve due to distortion at implant, fracture of the Elgiloy 
wireform, or physical or chemical deterioration of valve components    
– Tissue deterioration including infection, calcification, thickening, perforation, 
degeneration, suture abrasion, instrument trauma, and leaflet detachment from 
the valve stent posts 
 
Events potentially associated with the use of stented bioprosthetic heart valves include: 
– Angina 
– Cardiac arrhythmias 
– Endocarditis 
– Heart failure 
– Hemolysis 
– Hemolytic anemia 
– Hemorrhage  
– Local and/or systemic infection 
– Myocardial infarction 
– Prosthesis leaflet entrapment 
– Prosthesis nonstructural dysfunction 
– Prosthesis pannus 
– Prosthesis perivalvular leak 
– Prosthesis regurgitation 
– Prosthesis structural deterioration 
– Prosthesis thrombosis 
– Stroke 
– Thromboembolism 
 
It is possible that these complications could lead to: 
– Reoperation 
– Explantation 
– Permanent disability 
– Death 
 
These complications may present clinically as abnormal heart murmur, shortness of 
breath, exercise intolerance, dyspnea, orthopnea, anemia, fever, arrhythmia, 
hemorrhage, transient ischemic attack, stroke, paralysis, low cardiac output, pulmonary 
edema, congestive heart failure, cardiac failure, and myocardial infarct. 
 
 
Appendix 9: Page 7 of 32

1.5 
Assessment of Clinical Safety and Performance 
 
 
1.5.1 State of the Art 
 
A. 
Mechanical Valves 
Mechanical valves available for both the aortic and mitral position include the ball-and-
cage valves, single tilting disc prostheses, and bileaflet prostheses.  The ball-and-cage 
valve utilizes a metal cage housing a silicone elastomer ball.  The tilting disc prosthesis 
has a single circular occluder controlled by a metal strut.  Bileaflet prostheses two 
semicircular leaflets that rotate about struts attached to the valve housing. 
 
Mechanical valves have the following advantages as described in the ACC/AHA 2006 
Guidelines for the Management of Patients with Valvular Heart Disease and the 
Guidelines on the management of valvular heart disease published by the Task Force on 
the Management of Valvular Heart Disease of the European Society of Cardiology (ESC). 
− Standard implantation technique 
− Bileaflet valves are relatively quiet 
− Bileaflet valves appear to be mechanically stable 
− Bileaflet valves are relatively hemodynamically efficient 
 
Mechanical valves have the following disadvantages as described in the ACC/AHA 2006 
Guidelines for the Management of Patients with Valvular Heart Disease and the 
Guidelines on the management of valvular heart disease published by the Task Force on 
the Management of Valvular Heart Disease of the European Society of Cardiology (ESC). 
− Need for  anticoagulation therapy to prevent thromboembolism  
− Risk of bleeding complications 
− Risk of thromboembolism despite anticoagulation therapy 
− Increased risk of thromboembolism for mitral replacements 
− Risk of endocarditis 
− Hemodynamic inefficiency in smaller sizes 
− ball-and-cage valves are associated with noise 
− ball-and-cage valves are associated with hemodynamic inefficiency 
− ball-and-cage valves in the mitral position project into the outflow tract 
causing obstruction 
− single-disc valves are prone to severe hemodynamic compromise if disc 
thrombosis or immobility occurs 
 
B. 
Homografts or AutoGrafts 
Homograft valves donated by other patients and harvested after the patient expires are 
used as aortic replacements.  Pulmonary autografts are also used in the Ross procedure. 
 
Appendix 9: Page 8 of 32

Homograft or autograft valves have the following advantages as described in the 
ACC/AHA 2006 Guidelines for the Management of Patients with Valvular Heart Disease 
and the Guidelines on the management of valvular heart disease published by the Task 
Force on the Management of Valvular Heart Disease of the European Society of 
Cardiology (ESC). 
− Avoidance of early endocarditis 
− Low risk of thromboembolism 
− Excellent hemodynamic efficiency 
− Pulmonary autografts may grow in children 
 
Homograft or autograft valves have the following disadvantages as described in the 
ACC/AHA 2006 Guidelines for the Management of Patients with Valvular Heart Disease 
and the Guidelines on the management of valvular heart disease published by the Task 
Force on the Management of Valvular Heart Disease of the European Society of 
Cardiology (ESC). 
− Reduced availability when compared with xenografts/mechanical valves 
− Surgical procedure is more complicated than xenografts/mechanical valves 
− Reoperation after homograft AVR is more difficult 
 
 
Discussion 
 
In the 2008 edition of Cardiac Surgery in the Adult7
 
, Desai and Christakis discusses the 
balance of risk and benefits the surgeon and patient must make when selecting 
between the mechanical and biological valves. Structural deterioration, reoperation, 
thrombogenicity and bleeding complications are risks that must be taken into 
consideration, as well as the medical condition and age of the patient.   
Results from Edwards’ clinical trials and information available in the published literature 
demonstrate the safety and performance of pericardial valves, justifying their use in 
surgical treatment of valve disease.  Use of the mechanical valve needs to have the 
cumulative risk of lifelong anticoagulation taken into serious consideration, and 
pericardial valves present an alternative for patients who wish to avoid long term 
anticoagulation. 
 
Doenst et. al [2]  indicated the Carpentier-Edwards pericardial aortic valve has proved to 
have durability particularly in older patients, prompting a revival in its mitral 
counterpart.  The design of the mitral valve has enhanced the durability of the 
pericardium as a valve cusp. Cusps tears are a common cause of failure of previous 
pericardial valves and are rare with the Carpentier-Edwards pericardial valve. The table 
7 Desai N Di , Christakis G Ti . Bioprosthetic Aortic Valve Replacement: Stented Pericardial and Porcine Valves. 
Cohn Lh, ed. Cardiac Surgery in the Adult. New York: McGraw-Hill, 2008:857-894 
Appendix 9: Page 9 of 32

below (Table 1) demonstrates actuarial freedom from structural valve deterioration 
(SVD) by age group for patients receiving the Carpentier-Edwards pericardial valve in the 
mitral position, and confirms patient age is a major determinant of SVD of pericardial 
valves. 
 
Table 1: Actuarial freedom from structural valve deterioration by age group 
Age groups (yr) 
Number of patients 
5-year (%) 
10-year (%) 
≤ 40 
38 
97 
80 
41-50 
109 
100 
91 
51-60 
108 
99 
84 
61-70 
171 
100 
95 
> 70 
85 
100 
100 
 
Desai and Christakis8
 
, stated currently available pericardial valves have >90% freedom 
from structural valve dysfunction and >90% freedom from reoperation at 12-year 
follow-up, and without any valve failures in patients older than 65 years.  
Pericardial valves provide an option for mitral valve replacement in older patients with 
the need for reoperation as low, and can be used in younger patients with frequent 
monitoring of valve performance. 
 
1.5.2 Bench tests 
 
Refer to Design Dossier 
 
1.5.3 Clinical Data 
 
Since the designs of the 6900P, 6900PTFX, 7000TFX, 7200TFX, 7300 and 7300TFX valves 
are based on the model 6900 valve, the following clinical data applies to all models.  
Error! Reference source not found.Table 2 correlates the model 7200TFX sizes with the 
model 6900 data. 
 
Table 2:  Models 6900 and 7200TFX Size Correlation Table 
 
Size 
Model 6900  
25 mm 
27 mm 
29 mm 
31 mm 
33 mm 
Model 7200TFX 
27 
29 
31 
33 
35 
 
8 Desai N Di , Christakis G Ti . Bioprosthetic Aortic Valve Replacement: Stented Pericardial and Porcine Valves. 
Cohn Lh, ed. Cardiac Surgery in the Adult. New York: McGraw-Hill, 2008:857-894 
Appendix 9: Page 10 of 32

Model 6900  
Three (3) multi-center, non-randomized, prospective clinical studies were conducted 
with patients implanted with the Carpentier-Edwards PERIMOUNT Pericardial 
Bioprosthesis Model 6900 Mitral.  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, patients were implanted between 1984 
and 1986; in the second study, patients were implanted between 1989 and 1994; and in 
the third study, patients were implanted between 1996 and 1997.  Patients were 
evaluated preoperatively, intraoperatively/at discharge, at 1 year, and annually 
thereafter. 
 
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). 
 
In these pooled populations, there were a total of 212 (58.4%) males and 151 (41.6%) 
females with a mean age at implant (± standard deviation) of 66.1 (± 10.7) years. The 
indications for valve replacement were regurgitation (50.7%), stenosis (25.1%), mixed 
disease (16.0%) and none (8.3%). 
 
Model 6900P 
One (1) multi-center, non-randomized, prospective international clinical study was 
conducted with patients implanted with the Carpentier-Edwards PERIMOUNT 
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. 
 
The adverse event rates are based on two hundred and 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).  
 
Table 3 (model 6900) below 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. 
 
Appendix 9: Page 11 of 32

Table 3: Observed Adverse Event Rates for MVR and DVR (Model 6900) 
All patients analyzed: N = 363 Cumulative follow-up: 1100 patient-years 
Complications 
Early Events 
Late Events1 
Freedom from Event (%) [95% CI]2 
N 
% 
N 
% / pt-year 
1 year (n=287) 
5 years (n=141) 
8 years (n=18) 
All Mortality 
34 
9.4 
50 
4.7 
85.5 [81.8, 89.2] 75.4 [70.3, 80.6] 
65.4 [57.6, 73.2] 
Valve-related events 
 
 
 
 
 
 
 
Mortality (valve-related) 
0 
0 
16 
1.5 
97.7 [96.0, 99.4] 
95.3 [92.8, 97.8] 
91.9 [87.5, 96.4] 
Explants 
0 
0 
8 
0.7 
98.7 [98.0, 99.3] 
96.7 [95.3, 98.0] 
95.6 [93.9, 97.3] 
Reoperations 
2 
0.6 
12 
1.1 
97.1 [96.2, 98.1] 
95.1 [93.6, 96.6] 
93.0 [90.9, 95.1] 
Bleeding Event 
2 
0.6 
9 
0.8 
97.1 [95.2, 99.0] 
97.1 [95.2, 99.0] 
94.1 [88.2, 100] 
Endocarditis 
1 
0.3 
3 
0.3 
99.0 [97.9, 100] 
98.7 [97.4, 98.9] 
98.7 [97.4, 98.9] 
Hemolysis 
0 
0.0 
1 
0.1 
99.7 [99.0, 100] 
99.7 [99.0, 100] 
99.7 [99.0, 100] 
Nonstructural dysfunction 
0 
0.0 
3 
0.3 
100 [100, 100] 
99.3 [98.0, 100] 
98.3 [95.9, 100] 
Perivalvular leak (all) 
1 
0.3 
5 
0.5 
98.4 [97.0, 99.8] 
98.4 [97.0, 99.8] 
97.3 [94.9, 99.8] 
Structural valve deterioration 
0 
0.0 
5 
0.5 
100.0 [100, 100] 
97.6 [95.2, 100] 
92.8 [85.3, 100] 
Thromboembolism 
5 
1.4 
8 
0.7 
97.5 [95.8, 99.2] 
96.1 [93.8, 98.5] 
96.1 [93.8, 98.5] 
Thrombosis 
0 
0.0 
0 
0.0 
100.0 [100, 100] 
100.0 [100, 100] 
100.0 [100, 100] 
Notes: 
1. 
Late event rates were calculated as linearized rates (%/pt-yr) based on 1072.5 late patient-years (>30 days 
postoperatively) 
2. 
Freedom from event rates were calculated using the Kaplan-Meier method. Greenwood’s formula was used for 
calculation of the standard errors of these estimates. 
3. 
n = number of events 
 
Appendix 9: Page 12 of 32

 
Table 4 (model 6900P) 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). 
 
 
Table 4: Observed Adverse Event Rates (Model 6900P) 
All patients analyzed: N=209. Cumulative follow-up: 873.18 total pt-yrs.  
Complication 
Early Events 
Late Events 
Freedom from Event(%)[95% CI] 
n 
% 
n 
%/pt-yr 
1 year 
5 years 
Mortality (all) 
3 
1.4 
45 
5.3 
93.2[88.8,95.9] 
74.4[66.9,80.5] 
Valve-related events 
 
 
 
 
 
 
Mortality (valve-related) 
1 
0.5 
12 
1.4 
98.5[95.5,99.5] 
92.0[86.2,95.5] 
Explants 
1 
0.5 
8 
0.9 
97.5[94.0,98.9] 
96.5[92.2,98.5] 
Reoperations 
0 
0.0 
0 
0.0 
100.0[100,100] 
100.0[100,100] 
Bleeding Events 
5 
2.4 
13 
1.5 
96.1[92.3,98.0] 
91.9[86.5,95.2] 
Endocarditis 
1 
0.5 
3 
0.4 
99.5[96.6,99.9] 
97.1[92.1,98.9] 
Nonstructural Dysfunction 
0 
0.0 
1 
0.1 
99.5[96.4,99.9] 
99.5[96.4,99.9] 
Perivalvular leak(all) 
1 
0.5 
2 
0.2 
99.5[96.7,99.9] 
98.4[95.2,99.5] 
Structural Valve Deterioration 
0 
0.0 
2 
0.2 
100.0[100,100] 
99.0[93.2,99.9] 
Thromboembolism 
4 
1.9 
12 
1.4 
97.0[93.5,98.7] 
91.3[85.8,94.7] 
Thrombosis 
0 
0.0 
0 
0.0 
100.0[100,100] 
100.0[100,100] 
Notes:  
1. Late event rates were calculated as linearized rates (%/pt-yr) based on 856.24 late patient-years (> 30 
days postoperatively). 
2. Freedom from event rates was calculated using the Kaplan-Meier method.  Greenwood’s formula was 
used for calculation of the standard errors of these estimates. 
3. n = number of events. 
 
 
Table 5 (model 6900) and Table 6 (model 6900P) present, by valve size, the mean 
gradients and valve areas reported in echocardiograms performed on patients in the 
pooled study populations.  
 
Appendix 9: Page 13 of 32

 
Table 5: Effective Outcomes, Hemodynamic Results1 (Model 6900) 
Hemodynamic 
Parameter 
Results By Valve Size 
25 mm 
27 mm 
29 mm 
31 mm 
 
33 mm 
Discharge/Early Post-Implant (n=130, 109 MVR
2 and 21 DVR
3) 
Mean gradient4 
n = 3 
n = 23 
n = 36 
n = 23 
n = 3 
• mean ±sd 
5.7 ± 1.2 
4.2 ± 1.7 
4.2 ±1.7 
3.6 ±1.0 
7.5 ±5.8 
• min, max 
5, 7 
2, 9 
1, 8 
2, 5 
3, 14 
EOA5 
n = 1 
n = 17 
n = 22 
n = 25 
n = 5 
• mean ± sd 
1.5 
2.9 ± 0.9 
3.1 ± 0.9 
2.5 ± 0.7 
3.0 ± 1.2 
• min, max 
1.5, 1.5 
1.3, 4.1 
1.4, 4.2 
1.5, 3.8 
1.6, 4.9 
Regurgitation6 
n = 3 
n = 28 
n = 51 
n = 40 
n = 8 
0 
3/3 (100%) 
22/28 (79%) 
36/51 (71%) 
30/40 (75%) 
4/8 (50%) 
1+ 
0/3 (0%) 
5/28 (18%) 
13/51 (25%) 
7/40 (18%) 
4/8 (50%) 
2+ 
0/3 (0%) 
0/28 (0%) 
1/51 (2%) 
3/40 (7%) 
0/8 (0%) 
3+ 
0/3 (0%) 
0/28 (0%) 
1/51 (2%) 
0/40 (0%) 
0/8 (0%) 
4+ 
0/3 (0%) 
0/28 (0%) 
0/51 (0%) 
0/40 (0%) 
0/8 (0%) 
Not available 
0/3 (0%) 
1/28 (3%) 
0/51 (0%) 
0/40 (0%) 
0/8 (0%) 
3 to 6 Month Post-Implant Interval (n=49, 42 MVR2 and 7 DVR3) 
Mean gradient4 
n = 5 
n = 19 
n = 15 
n = 5 
n = 2 
• mean ±sd 
6.4 ±1.7 
5.3 ±5 
3.4 ±1.2 
4 ±1.9 
4 ±0 
• min, max 
5, 9 
2, 25 
2, 6 
2, 7 
4, 4 
EOA5 
n = 5 
n = 18 
n = 13 
n = 5 
n = 2 
• mean ± sd 
2.9 ± 0.8 
2.6 ± 0.7 
2.8 ± 0.6 
2.9 ± 0.3 
2.6 ± 1 
• min, max 
1.8, 3.6 
1.5, 5 
2, 3.8 
2.4, 3.3 
2, 3.3 
Regurgitation
6 
n = 5 
n = 21 
n = 15 
n = 6 
n = 2 
0 
3/5 (60%) 
17/21 (81%) 
6/15 (40%) 
4/6 (67%) 
1/2 (50%) 
1+ 
0/5 (0%) 
4/21 (19%) 
8/15 (53%) 
2/6 (33%) 
0/2 (0%) 
2+ 
1/5 (20%) 
0/21 (0%) 
1/15 (7%) 
0/6 (0%) 
1/2 (50%) 
3+ 
0/5 (0%) 
0/21 (0%) 
0/15 (0%) 
0/6 (0%) 
0/2 (0%) 
4+ 
1/5 (20%) 
0/21 (0%) 
0/15 (0%) 
0/6 (0%) 
0/2 (0%) 
Not available 
0/5 (0%) 
0/21 (0%) 
0/15 (0%) 
0/6 (0%) 
0/2 (0%) 
1 to 2 Year Post-Implant Interval (n=131, 114 MVR2 and 17 DVR3) 
Mean gradient4 
n = 3 
n = 40 
n = 47 
n = 27 
n = 4 
• mean ±sd 
5.2 ±0.7 
4.1 ± 1.6 
3.5 ±1.8 
3.1 ± 1.4 
2.1 ±0.5 
• min, max 
4.7, 6 
1, 7 
1, 10 
1,7 
1.5, 2.7 
EOA5 
n = 2 
n = 35 
n = 46 
n = 29 
n = 5 
• mean ±sd 
1.8 ±0.4 
2.3 ±0.6 
2.6 ±0.5 
2.6 ±0.7 
2.5 ±0.5 
• min, max 
1.5, 2.0 
1.2, 3.5 
1.1, 3.7 
1.1, 3.7 
2.1, 3.2 
Regurgitation6 
n = 4 
n = 42 
n = 51 
n = 29 
n = 5 
0 
2/4 (50%) 
31/42 (74%) 
36/51 (71%) 
17/29 (59%) 
3/5 (60%) 
1+ 
1/4 (25%) 
9/42 (21%) 
11/51 (21%) 
8/29 (27%) 
1/5 (20%) 
2+ 
1/4 (25%) 
2/42 (5%) 
4/51 (8%) 
2/29 (7%) 
1/5 (20%) 
3+ 
0/4 (0%) 
0/42 (0%) 
0/51 (0%) 
2/29 (7%) 
0/5 (0%) 
4+ 
0/4 (0%) 
0/42 (0%) 
0/51 (0%) 
0/29 (0%) 
0/5 (0%) 
Not available 
0/4 (0%) 
0/42 (0%) 
0/51 (0%) 
0/29 (0%) 
0/5 (0%) 
5 Year Post-Implant Interval (n=11, 9 MVR2 and 2 DVR3) 
Mean gradient4 
n = 0 
n = 6 
n = 5 
n = 0 
n = 0 
• mean ±sd 
N/A 
8.8 ±8.1 
5.1 ±2.3 
N/A 
N/A 
• min, max 
N/A 
4, 25 
3, 8 
N/A 
N/A 
EOA5 
n = 0 
n = 2 
n = 4 
n = 0 
n = 0 
• mean ±sd 
N/A 
2.0 ±1.5 
2.9 ±0.6 
N/A 
N/A 
• min, max 
N/A 
1.0, 3.1 
2.1, 3.5 
N/A 
N/A 
Regurgitation6 
n = 0 
n = 6 
n = 5 
n = 0 
n = 0 
0 
0/0 (0%) 
4/6 (66%) 
2/5 (40%) 
0/0 (0%) 
0/0 (0%) 
1+ 
0/0 (0%) 
1/6 (17%) 
3/5 (60%) 
0/0 (0%) 
0/0 (0%) 
2+ 
0/0 (0%) 
1/6 (17%) 
0/5 (0%) 
0/0 (0%) 
0/0 (0%) 
3+ 
0/0 (0%) 
0/6 (0%) 
0/5 (0%) 
0/0 (0%) 
0/0 (0%) 
4+ 
0/0 (0%) 
0/6 (0%) 
0/5 (0%) 
0/0 (0%) 
0/0 (0%) 
Not available 
0/0 (0%) 
0/6 (0%) 
0/5 (0%) 
0/0 (0%) 
0/0 (0%) 
Notes: 
Appendix 9: Page 14 of 32

1. Hemodynamic evaluations were performed using transthoracic echocardiography (TTE) and in some cases, transesophageal echocardiography 
(TEE) 
2. MVR = mitral valve replacement 
3. DVR = double valve replacement 
4. Mean gradient in mmHg 
5. EOA: Effective Orifice Area, cm2 
6. Regurgitation = none, 0; mild, 1+; moderate, 2+; 
moderate/severe, 3+; severe, 4+ 
 
Table 6: Effectiveness Outcomes, Hemodynamic Results (Model 
6900P)1 
 
Results By Valve Size 
Hemodynamic 
Parameter 
25mm 
27mm 
29mm 
31mm 
33mm 
Discharge/Early Post-Implant 
Mean gradient2 
n=24 
n=35 
n=83 
n=42 
n=16 
Mean+/-SD 
6.4+/-1.87 
4.4+/-1.52 
3.4+/-1.47 
3.3+/-1.20 
4.0+/-1.38 
Min,Max 
3, 10 
1.96, 8 
1.4, 9 
1, 7 
1.5, 6.91 
EOA3 
n=8 
n=27 
n=77 
n=41 
n=16 
Mean+/-SD 
2.7+/-0.87 
2.8+/-0.58 
2.9+/-0.93 
2.5+/-0.67 
2.4+/-0.52 
Min,Max 
1.46, 4.4 
1.5, 3.9 
1.58, 6 
1.32, 4.2 
1.55, 3.31 
Regurgitation4 
n=27 
n=37 
n=83 
n=43 
n=17 
Trivial / None 
19/27(70%) 
29/37(78%) 
76/83(92%) 
39/43(91%) 
15/17(88%) 
1+ Mild 
6/27(22%) 
7/37(19%) 
7/83(8%) 
4/43(9%) 
1/17(6%) 
2+ Moderate 
1/27(4%) 
1/37(3%) 
0/83(0%) 
0/43(0%) 
0/17(0%) 
3+ Moderate/Severe 
0/27(0%) 
0/37(0%) 
0/83(0%) 
0/43(0%) 
1/17(6%) 
4+ Severe 
0/27(0%) 
0/37(0%) 
0/83(0%) 
0/43(0%) 
0/17(0%) 
Not Available 
1/27(4%) 
0/37(0%) 
0/83(0%) 
0/43(0%) 
0/17(0%) 
3 to 6 Month Post-Implant Interval 
Mean gradient 
n=0 
n=4 
n=3 
n=2 
n=0 
Mean+/-SD 
0+/-0 
4.4+/-2.25 
2.3+/-0.89 
6.6+/-2.05 
0+/-0 
Min,Max 
0, 0 
2.5, 7.5 
1.3, 3 
5.1, 8 
0, 0 
EOA 
n=0 
n=3 
n=3 
n=1 
n=1 
Mean+/-SD 
0+/-0 
2.4+/-0.74 
3.2+/-0.88 
2.5+/-0.00 
1.2+/-0.00 
Min,Max 
0, 0 
1.6, 3 
2.3, 4.05 
2.47, 2.47 
1.22, 1.22 
Regurgitation 
n=0 
n=5 
n=3 
n=2 
n=2 
Trivial / None 
0 
3/5(60%) 
2/3(67%) 
2/2(100%) 
2/2(100%) 
1+ Mild 
0 
1/5(20%) 
1/3(33%) 
0/2(0%) 
0/2(0%) 
2+ Moderate 
0 
1/5(20%) 
0/3(0%) 
0/2(0%) 
0/2(0%) 
3+ Moderate/Severe 
0 
0/5(0%) 
0/3(0%) 
0/2(0%) 
0/2(0%) 
4+ Severe 
0 
0/5(0%) 
0/3(0%) 
0/2(0%) 
0/2(0%) 
Not Available 
0 
0/5(0%) 
0/3(0%) 
0/2(0%) 
0/2(0%) 
1 Year Post-Implant Interval 
Mean gradient 
n=16 
n=27 
n=63 
n=34 
n=15 
Mean+/-SD 
5.9+/-2.36 
4.0+/-1.45 
3.0+/-1.61 
3.3+/-1.26 
3.4+/-1.25 
Min,Max 
3, 12 
2, 7 
1, 12 
1.5, 7 
1.9, 6.3 
EOA 
n=3 
n=21 
n=59 
n=32 
n=15 
Mean+/-SD 
2.3+/-0.16 
2.4+/-0.76 
2.6+/-0.74 
2.5+/-0.67 
2.3+/-0.83 
Min,Max 
2.09, 2.4 
1.27, 4.76 
1.5, 5.7 
1.5, 4 
1.2, 3.8 
Regurgitation 
n=20 
n=28 
n=65 
n=34 
n=16 
Trivial / None 
17/20(85%) 
24/28(86%) 
53/65(82%) 
29/34(85%) 
13/16(81%) 
1+ Mild 
3/20(15%) 
3/28(11%) 
6/65(9%) 
3/34(9%) 
3/16(19%) 
2+ Moderate 
0/20(0%) 
0/28(0%) 
3/65(5%) 
2/34(6%) 
0/16(0%) 
3+ Moderate/Severe 
0/20(0%) 
0/28(0%) 
1/65(2%) 
0/34(0%) 
0/16(0%) 
4+ Severe 
0/20(0%) 
0/28(0%) 
0/65(0%) 
0/34(0%) 
0/16(0%) 
Not Available 
0/20(0%) 
1/28(4%) 
2/65(3%) 
0/34(0%) 
0/16(0%) 
Notes: 
1.  Hemodynamic evaluations were performed using transthoracic echocardiography (TTE) and in some cases, 
transesophageal echocardiography (TEE). 
2.  Mean gradient in mmHg 
3.  EOA: Effective Orifice Area, cm2 
4.  Regurgitation = Trivial/none, 0; mild, 1+; moderate, 2+; moderate/severe, 3+; severe, 4+ 
 
Appendix 9: Page 15 of 32

 
 
Table 7 (model 6900) and Table 8 (model 6900P) presents data comparing preoperative 
NYHA Functional Class to postoperative NYHA Functional Class. 
 
Table 7: Effectiveness Outcomes, Functional NYHA (Model 6900) 
 
Preoperative 
Assessment 
Postoperative Assessments 
 
1 to 2 Year 
5 Year 
NYHA Functional Class 
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 8: Effectiveness Outcomes, Functional NYHA (Model 6900P) 
 
Preoperative 
Assessment 
Postoperative Assessments 
 
1 Year 
5 Year 
NYHA Functional Class 
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. 
 
 
1.5.4 Literature Review 
 
The literature review has been conducted according to MEDDEV 2.7.1. April 2003 
“Guidelines on Medical Devices, Evaluation of Clinical Data.”  The objective of this 
literature search was to demonstrate that the Carpentier-Edwards PERIMOUNT 
pericardial bioprostheses are safe and perform as intended by the manufacturer.  The 
types of studies that are relevant to this objective are specified.  The relevance of data 
and the extent to which the scientific articles relate to the device in question and to 
similar devices are shown below. 
 
The scientific literature was searched for articles related to all of the Edwards  
pericardial bioprostheses using PubMed (www.pubmed.gov).  The following key words 
search terms were entered in the online search engine with publication dates from 
January 01, 2003 to March 31, 2010:   
 
- 
Carpentier-Edwards pericardial  
Appendix 9: Page 16 of 32

- 
Edwards pericardial  
- 
Carpentier Edwards bovine  
- 
Edwards bovine  
- 
Bovine pericardial valve 
- 
Stented bovine valve 
- 
Stented pericardial valve 
- 
Carpentier-Edwards valve 
- 
Pericardial valve 
- 
Carpentier-Edwards PERIMOUNT Plus 
- 
Edwards PERIMOUNT Plus 
- 
PERIMOUNT Plus 
- 
Carpentier-Edwards PERIMOUNT Mitral 
- 
Edwards PERIMOUNT Mitral 
- 
PERIMOUNT Mitral 
- 
6900P 
- 
Carpentier-Edwards PERIMOUNT Magna Mitral 
- 
Carpentier-Edwards PERIMOUNT Magna Mitral Ease 
- 
Edwards PERIMOUNT Magna Mitral 
- 
Edwards PERIMOUNT Magna Mitral Ease 
- 
PERIMOUNT Magna Mitral 
- 
PERIMOUNT Magna Mitral Ease 
- 
Magna Mitral Ease  
- 
Magna Mitral 
- 
7000 
- 
7200 
 
The search yielded 14 journal articles published from 2003-2010 which described 
various techniques of valve replacement with the Carpentier-Edwards PERIMOUNT 
pericardial bioprostheses, echo studies, case studies and in-vitro studies.  The abstracts 
were reviewed and pertinent articles are presented below.   
 
 [1] Daebritz et al reported results on a study of mitral valve replacements including the 
stented Perimount mitral valve.  BACKGROUND: Current heart valve prostheses are 
constructed mimicking the native aortic valve. Special hemodynamic characteristics of 
the mitral valve such as a nonaxial central inflow with creation of a left ventricular 
vortex have so far not been taken into account. A new polycarbonaturethane (PCU) 
bileaflet heart valve prosthesis with special design for the mitral position is introduced, 
and results of animal testing are presented. METHODS AND RESULTS: After in vitro 
testing, 7 PCU-prostheses and 7 commercial bioprostheses (Perimount, n=4; Mosaic, 
n=3) were implanted in mitral position into growing Jersey calves (age 3-5 months, 
weight 60-97 kg) for 20 weeks. 2-Dimensional echocardiography was performed after 
implantation and before sacrification. Autopsy included histologic, radiographic, and 
electron microscopic examination of the valves. In vitro durability was proven for >15 
Appendix 9: Page 17 of 32

years. After implantation 2-dimensional-echocardiography showed no relevant gradient 
or regurgitation of any prosthesis. Clinical course of the animals with PCU valves was 
excellent. In contrast, 5 of 7 calves with bioprostheses were sacrificed after 1-9 weeks 
because of congestive heart failure. 2-Dimensional echocardiography of the PCU valves 
after 20 weeks showed mild leaflet thickening with trivial regurgitation; mean gradient 
was 8.1+/-5.0 mm Hg (weight: 160-170 kg). The explanted PCU prostheses revealed mild 
calcification and no structural degeneration. All of the Perimount bioprostheses were 
severely calcified and degenerated after 11+/-7 weeks. One Mosaic bioprosthesis was 
thrombosed after 1 week, and 2 showed severe and mild-to-moderate degeneration 
after 4 and 22 weeks, respectively. CONCLUSIONS: Polycarbonaturethane valve 
prostheses with special design for mitral position show excellent hemodynamic 
performance and durability in vivo. Calcification and structural changes are mild 
compared with bioprostheses. Controlled clinical studies are planned. 
 
[2] Doenst et al reported results on a study of mitral valve replacements including the 
stented Perimount mitral valve.  Pericardial valve bioprostheses were introduced in 
early 1970s and were widely used in the 1980s. The long-term results with the Ionescu-
Shiley valve, the first commercially available pericardial valve, were disappointing 
because of high rate cusp tears during the first decade after implantation. The 
enthusiasm for this type of bioprosthetic valve was further hampered by the premature 
failure of the Hancock pericardial valve. The long-term results of aortic valve 
replacement with the Carpentier-Edwards pericardial valve, which was introduced in 
1981, indicated that that valve was durable and the issue of cusp tears had been 
resolved by an appropriate design. This knowledge prompted surgeons to revisit the 
merits of pericardial valves for mitral valve replacement and several other pericardial 
valves are now commercially available. The largest data on long-term results are with 
the Carpentier-Edwards pericardial mitral valve. The reported freedom from structure 
valve failure ranged from 69% to 85% at 10 years in patient population with mean age of 
60 to 70 years. Young age is a major determinant of valve failure, which is largely due to 
calcification. There are also long-term data, albeit more limited on the Sorin Pericarbon 
and Mitroflow valves used for mitral valve replacement. This paper reviews the 
published experience with various pericardial bioprosthetic valves used for mitral valve 
replacement during the past 3 decades. 
 
[3] Goetze et al reported results on a study of mitral valve replacements including the 
stented Perimount mitral valve.  We sought to determine the hemodynamic 
performance of the Carpentier-Edwards Perimount pericardial valve in the mitral 
position. We reviewed the Doppler echocardiographic data on 189 patients (110 
women; 68 +/- 12 years of age) who were implanted with this valve (7.6 days +/- 13 
postoperatively) at our institution between September 2000 and May 2002. The average 
ejection fraction was 47%. For all valves, the peak velocity was 1.9 +/- 0.3 m/s, peak 
gradient was 15 +/- 4.8 mm Hg, and mean gradient was 5.8 +/- 2 mm Hg. The pressure 
half-time was 93 +/- 24 milliseconds, with a calculated effective orifice area of 2.5 +/- 
Appendix 9: Page 18 of 32

0.6 cm2. The average effective orifice area by continuity equation (83 valves) was 1.5 +/- 
0.5 cm2. The mitral regurgitation was graded mild or less in 97.5% of all valves. This is 
the largest series establishing the favorable hemodynamic behavior of the different 
sizes of a new Perimount mitral valve, and the reported data could serve as a reference. 
 
[4] Kheradvar et al reported results on a study of mitral valve replacements including 
the stented Perimount mitral valve.  In vitro assessment of different profiles for 
prosthetic mitral valves can result in better understanding of the physics of transmitral 
flow for each design. It has been postulated that decreasing the profile height of the 
mitral bioprosthetic valve has potential clinical benefit. In the present study, we 
compared the atrial and ventricular flow characteristics in different conditions using 
Carpentier-Edwards Perimount mitral valves with various profile heights. Each valve was 
placed at the intersection of the left ventricle, made of transparent silicone rubber, and 
the left atrium in Caltech's left heart pulsed flow simulator system. Digital particle image 
velocimetry has been used as the quantitative flow visualization technique. With the 
intention of studying the blood wash out around each valve, circulation and particle 
residence time were computed based on the vorticity and velocity fields around each 
valve, respectively. Results show that by increasing the profile's height at the atrial side 
of the valve, the magnitude of circulation near the atrial side of the valve decreases 
while particle residence time increases. However, extreme reduction of profile height in 
the ventricular side may increase the magnitude of circulation around the valve and 
decrease the particle residence time. 
 
[5] Murayama et al reported results on a case of mitral valve replacements including the 
stented Perimount mitral valve.  We report the case of a mitral Carpentier-Edwards 
pericardial bioprosthesis that was explanted from a 43-year-old female patient because 
of structural valve deterioration 16 years following implantation. Upon removal, the 
prosthesis was found to be discolored and all leaflets were stiff and hard, showing 
extensive calcification, pannus overgrowth, leaflet hematoma, and multiple disruptions. 
One leaflet presented a wavy free margin due to commissural disruptions, leading to 
incomplete cusp coaptation. The accumulated physical symptoms of the patient were 
consistent with these findings. 
 
[6] Tateishi et al reported results on a case of mitral valve replacements of a stented 
Perimount mitral valve.  A 73-year-old woman who underwent mitral valve replacement 
with a 31 mm Carpentier Edwards Pericardial Xenograft 19 years ago. She revealed 
sudden onset of a grade IV/VI a seagull like diastolic murmur at the apex, and severe 
hematuria. Echocardiography demonstrated severe mitral regurgitation. These findings 
were consistent with acute primary tissue valve failure. Therefore we performed 
emergency reoperation. At operation, valve leaflet was torn at the commissural stitch, 
and bioprosthesis strut was buried in the left posterior ventricular wall. The mitral 
prosthetic valve replaced with a 25 mm CarboMedics OptiForm using a technique of 
Appendix 9: Page 19 of 32

valve-in-valve replacement. This procedure would be one option for replacement of 
bioprosthetic mitral valve 
 
[7] Chambers et al reported that stented bovine pericardial valve might be less 
obstructive than a stented porcine valve. This study compared early hemodynamic 
function in a prospective series of 99 patients randomized to receive either a Mosaic or 
Perimount replacement aortic valve. Echocardiography was performed early after 
surgery and at 1 year after surgery. Patients also filled in psychologic questionnaires and 
underwent a 6-minute walk. The groups were matched demographically. The Perimount 
valve was significantly less obstructive in terms of mean pressure difference (11 +/- 5 vs. 
17 +/- 7 mm Hg; P < .0001), with a trend in favor of a larger effective orifice area (1.47 
+/- 0.45 vs. 1.28 +/- 0.46 cm (2); P = .05) postoperatively. There were no differences in 
left ventricular mass regression, aortic regurgitation, 6-minute walk, psychologic 
questionnaires, or mortality and clinical events. The stented bovine pericardial valve 
was less obstructive than the stented porcine valve. Both valves were associated with 
similar and significant improvements in quality of life, exercise ability, and regression of 
left ventricular mass. 
 
[8] Risteski et al reported on randomized trials comparing stentless to stented 
bioprostheses for aortic valve replacement in elderly are scarce. The aim of this study 
was early and mid-term evaluation of these bioprostheses, with regards to clinical 
outcome and hemodynamic performance. Between September 1999 and January 2001, 
40 patients with aortic stenosis, over the age of 75 years, were randomly assigned to 
receive either the stented Perimount (n=20) or the stentless Prima Plus (n=20) 
bioprosthesis. Clinical outcomes, left ventricular mass regression, effective orifice area, 
ejection fraction and mean gradients were evaluated at discharge, six months, one year 
and five years after surgery. At five years, there were 5/20 (25%) deaths in the stentless 
group and 6/20 (30%) deaths in the stented group (all non-valve-related). There was one 
case of endocarditis in each group, early postoperatively. Overall, a significant decrease 
in left ventricular mass was found five years postoperatively. However, there was no 
significant difference in the rate and completeness of LV-mass regression between the 
groups (LV mass index 114+/-34.1 vs. 120+/-27.2). Furthermore, hemodynamic 
performance of the valves (mean gradient of 9.9+/-4.8 mmHg vs. 10.2+/-4.2 mmHg) did 
not differ significantly between the groups. At five years, stentless valves were not 
superior to the stented valves, with regards to hemodynamic performance, regression 
of left ventricular mass and clinical outcome. 
 
 [9] Accola et al  reported that aortic valve dysfunction is the most common form of 
valvular heart disease. As the population continues to age, a greater number of patients 
will become candidates for aortic valve replacement (AVR); hence, prosthetic valve 
choice becomes of paramount importance. A retrospective analysis was conducted on 
801 patients aged > or =65 years who underwent isolated AVR or AVR + coronary artery 
Appendix 9: Page 20 of 32

bypass grafting (CABG) between January 1989 and June 2003 with a Carpentier Edwards 
Perimount (CEP) pericardial bioprosthesis (n = 398) or a St. Jude Medical (SJM) 
mechanical valve (n = 403). The mean age of CEP patients was 74.5 years (range: 65-89 
years), and of SJM patients 73.9 years (range: 65-90 years). The follow up was 96.2% 
and 96.5% complete for CEP and SJM patients, respectively. Propensity scoring was used 
to establish homogeneity of the groups and reduce bias. The operative mortality was 
4.0% (n = 16) among CEP patients and 6.5% (n = 26) among SJM patients. Predictors of 
hospital mortality included: peripheral vascular disease (p = 0.018), surgical urgency (p = 
0.010), preoperative intra-aortic balloon pump (IABP) (p = 0.010), intraoperative 
perfusion time (p = 0.046) and intraoperative IABP (p = 0.001). Postoperative 
morbidities were similar for the two groups. The mean follow up was 72.4 and 59.2 
months for CEP and SJM patients, respectively. The five-year actuarial survival was 70.9 
+/- 2.3% for CEP and 71.8 +/- 2.4% for SJM patients; at 10 years the actuarial survival 
was 32.6 +/- 3.3% and 38.2 +/- 3.8%, respectively. Freedom from reoperation for AVR, 
stroke and non-fatal myocardial infarction was 98.8% (159/161), 99.4% (160/161) and 
99.4% (160/161), respectively, in CEP patients, and 100.0% (220/220), 97.7% (215/220) 
and 97.7% (215/220), respectively, in SJM patients (p = NS). Predictors of late death (>30 
days) included chronic obstructive pulmonary disease (p = 0.001) and mechanical valve 
replacement (p = 0.001). In comparable elderly patients, the outcomes of CEP and SJM 
valves after AVR showed no significant differences in hospital morbidity, mortality, mid-
term survival or late cardiac events. However, the cumulative risk of lifelong 
anticoagulation with a mechanical valve is a serious consideration that must be factored 
into the selection algorithm. 
 [10] Kume et al reported on a study to evaluate the impact of Doppler-derived energy 
loss coefficient (ELCo) on the regression of left ventricular (LV) hypertrophy after aortic 
valve replacement (AVR) in patients with severe aortic stenosis. Twenty-four patients 
with severe aortic stenosis who underwent AVR with Carpentier-Edwards pericardial 
bioprosthetic valves (valve size 19 mm, n = 16; valve size 21 mm, n = 8) were examined. 
Within 12 months after AVR, follow-up echocardiography and Doppler measurements 
were performed. The effect of AVR was quantified on the basis of absolute and relative 
LV mass regression. There were significant correlations between indexed ELCo and 
absolute (r = 0.50, P = .013) and relative (r = 0.48, P = .018) LV mass regression. The 
mean value of relative LV mass regression was 25%, and a cutoff value of 0.9 cm(2)/m(2) 
for indexed ELCo could detect patients with relative LV mass regression > 25% after AVR 
with sensitivity of 71% and specificity of 100%. ELCo, which can be calculated 
noninvasively from echocardiography, might be an important value to relate to LV mass 
regression in patients after AVR. 
 [11] Hilker et al reported observations among Karlsburg patients in 2006 revealed that 
the majority of very low platelet levels inducing postoperative heparin-induced-
thrombocytopenia (HIT)-diagnostics with at the end negative results appeared related 
to aortic valve replacement (AVR) with stentless bioprostheses. We compared the 
postoperative courses of platelet counts in patients having had AVR with stentless 
Appendix 9: Page 21 of 32

prostheses (Sorin Biomedica Freedom Solo [SOLO]) or stented prostheses (Carpentier 
Edwards Perimount [PM]). Between February 2005 and April 2007, 209 patients 
received AVR with SOLO, in 137 patients a PM-prosthesis was implanted. The mean 
platelet levels were compared from the first up to the fifth postoperative day. A higher 
occurrence of platelet levels below 100 Gpt/l between the second and the fifth 
postoperative day was found in the SOLO-group (71.9%) compared with the other 
biological substitute PM (36.6%). Differences in platelet counts between SOLO- and PM-
subgroups were measured for day 2 (P=0.03), day 3 (P=0.0004) day 4 (P=0.0007), day 5 
(P=0.0002) and at discharge (P<0.0001). Following intervention with conventional 
biological AVR, differences in the postoperative recovery of platelet counts can be 
detected, depending on the prosthesis used. The causes for and the clinical implications 
of this phenomenon are not yet assessed. 
 
 
[12] Kubota et al reported a case of Carpentier-Edwards PERIMOUNT (CEP) mitral 
pericardial bioprosthesis explanted 22 years after the valve replacement. This patient 
underwent the previous replacement at the age of 50. The extracted bioprosthesis 
showed three rigid leaflets, one of which had a tear causing severe mitral regurgitation. 
The X-ray demonstrated calcification of varied extent among these leaflets, ranging 
from none to severe. When leaflet calcification is suppressed, perhaps the lifespan of a 
CEP valve can be prolonged more than previously expected. When a literature search 
was conducted, this case was found to represent the longest reported interval from the 
implantation of a CEP valve in the mitral position to the explantation as a result of 
severe mitral regurgitation caused by structural valve deterioration (SVD). 
 
[13] M Thalmann et al  in a letter to Editor, regarding the world's first implant of a  
23 mm Carpentier-Edwards Perimount Magna mitral bioprosthesis, pointed out the 
need for appropriate sizing to avoid patient-prosthesis mismatch and infrequent but 
potentially lethal LV rupture. 
 
 
[14] Alsoufi B, et al reported the ideal valve substitute in children does not exist. Biologic 
and bioprosthetic valves do not require anticoagulation however their use is 
complicated by accelerated degeneration and requirement for reoperation. We examine 
results following mitral (MVR) or aortic (AVR) replacement with biologic and 
bioprosthetic valves at our institution. METHODS: Medical records of children who 
underwent AVR or MVR from 1986 to 2006 were reviewed. Median follow-up duration 
was 10.5 years. Competing-risks methodology determined time-related prevalence and 
associated factors for three mutually exclusive end states: death, valve reoperation, and 
survival without subsequent reoperation. RESULTS: One hundred and ten children (age 
15.6+/-2.6 years, 80% females) underwent 123 valve replacements with biologic and 
bioprosthetic substitutes including 87 MVR and 36 AVR (13 had both). Underlying 
pathology was mainly rheumatic fever (91%). Thirty-nine patients (35%) had undergone 
a previous cardiac surgery. Most common mitral substitute was Hancock (73%) and 
Appendix 9: Page 22 of 32

homograft (8%); most common aortic substitute was homograft (41%) and Carpentier-
Edwards (39%). Competing-risks analysis showed 15 years after valve replacement, 16% 
of patients had died without subsequent reoperation, 66% underwent valve 
reoperations, and only 18% remained alive without further reoperation. Factors 
associated with increased reoperation risk included younger age at surgery (p=0.005), 
AVR (p=0.005), male gender (p=0.02) and homograft use (p=0.007) especially in the 
mitral position (p=0.002). Fifteen-year freedom from endocarditis was 97% while 
freedom from bleeding and thromboembolic complications was 100%. Majority of 
patients (95%) were in NYHA functional classes I/II at last follow-up. CONCLUSION: 
While valve reoperation is inevitable following AVR and MVR with biologic and 
bioprosthetic substitutes, favorable results such as low valve-related morbidity rate, 
good long-term survival and functional status encourage their consideration as valid 
replacement alternatives in selected children, especially females. Valve durability is 
higher in the mitral position and longevity of bioprosthetic valves is greater than that of 
homografts especially in the mitral position. 
Appendix 9: Page 23 of 32

1.5.5 Marketing History 
 
The approval dates for each PERIMOUNT valve are shown below in Table 9.  
 
Table 9:  Global product approvals  
Model 
Europe 
Australia 
Canada 
Japan 
US 
6900P 
May 2000 
Oct 1991 
Sept 1998 
Apr 2007 
Nov 2001 
6900PTFX 
Apr 2004 
Sep 2005 
Dec 2007 
NA 
Jan 2004 
7000 
NA 
Nov 2008 
Nov 2005 
NA 
Aug 2008 
7000TFX 
Aug 2005 
Nov 2008 
Nov 2005 
NA 
Aug 2008 
7200TFX 
Mar 2010 
NA 
NA 
NA 
Jul 2009 
 
  
 
 
 
 
 
 
 
 
9: Page 24 of 32

 
1.5.6 Post Market Surveillance 
 
 
  
 
 
 
 
All expiration, reoperations, explants and complications are evaluated for their 
relationship to the valve, with special attention being paid to incidences of angina, 
anticoagulant related hemorrhage, arrhythmia, cardiac arrest, endocarditis, heart failure, 
hemolysis, myocardial infarction, nonstructural dysfunction, perivalvular leak, structural 
deterioration, thromboembolism, thrombosis and unacceptable hemodynamics. 
 
All cardiovascular related symptoms, such as abnormal heart murmur, shortness of 
breath, exercise intolerance, dyspnea, orthopnea, anemia, fever, transient ischemic 
attack, stroke, paralysis, low cardiac output and pulmonary edema are assessed as to 
their relation to the valve. 
 
The information used to perform this evaluation is taken from the complications 
handled through the Edwards complaint-handling system, and from supporting 
documentation, i.e., autopsy reports and expiration summaries.  When the review is 
inconclusive as to valve relatedness, a conservative choice is made and the complication 
is classified as “valve-related.” 
 
 
 
 
 
 
 
 
 
 
   
Appendix 9: Page 25 of 32

 
  
 
Appendix 9: Page 27 of 32

3 
References 
 
1. Daebritz SH, Sachweh JS, Hermanns B, Fausten B, Franke A, Groetzner J, 
Klosterhalfen B, Messmer BJ. Introduction of a flexible polymeric heart valve 
prosthesis with special design for mitral position. Circulation. 2003 Sep 9;108 Suppl 
1:II134-9. 
 
2. Doenst T, Borger MA, David TE. Long-term results of bioprosthetic mitral valve 
replacement: the pericardial perspective. J Cardiovasc Surg (Torino). 2004 
Oct;45(5):449-54.  
 
3. Goetze S, Brechtken J, Agler DA, Thomas JD, Sabik JF 3rd, Jaber WA. In vivo short-
term Doppler hemodynamic profiles of 189 Carpentier-Edwards Perimount 
pericardial bioprosthetic valves in the mitral position. J Am Soc Echocardiogr. 2004 
Sep;17(9):981-7.  
 
4. Kheradvar A, Kasalko J, Johnson D, Gharib M. An in vitro study of changing profile 
heights in mitral bioprostheses and their influence on flow. ASAIO J. 2006 Jan-
Feb;52(1):34-8. 
 
5. Murayama H, Watanabe T, Yano T, Kida N, Hatano Y, Ohara K, Kobayashi A. The case 
of an explanted 16-year-old mitral Carpentier-Edwards pericardial bioprosthesis. J 
Artif Organs. 2006;9(4):259-62. Epub 2006 Dec 21.  
 
6. Tateishi M, Koide M, Kunii Y, Watanabe K, Ohsawa M. [Valve-in-valve replacement of 
primary tissue valve failure of bovine pericardial valve minor] Kyobu Geka. 2006 
Jan;59(1):61-4.  
 
7. Chambers JB, Rajani R, Parkin D, Rimington HM, Blauth CI, Venn GE, Young CP, 
Roxburgh JC. Bovine pericardial versus porcine stented replacement aortic valves: 
early results of a randomized comparison of the Perimount and the Mosaic valves. J 
Thorac Cardiovasc Surg. 2008 Nov;136(5):1142-8. Epub 2008 Aug 15 
 
8. Risteski PS, Martens S, Rouhollahpour A, Wimmer-Greinecker G, Moritz A, Doss M. 
Prospective randomized evaluation of stentless vs. stented aortic biologic prosthetic 
valves in the elderly at five years. Interact Cardiovasc Thorac Surg. 2009 
Apr;8(4):449-53. Epub 2009 Jan 6 
 
9. Accola KD, Scott ML, Palmer GJ, Thompson PA, Sand ME, Suarez-Cavalier JE, Bott JN, 
Ebra G. Surgical management of aortic valve disease in the elderly: A retrospective 
comparative study of valve choice using propensity score analysis. J Heart Valve Dis. 
2008 Jul;17(4):355-64; discussion 365 
 
Appendix 9: Page 31 of 32

10. Kume T, Okura H, Kawamoto T, Watanabe N, Neishi Y, Hayashida A, Tanemoto K, 
Yoshida K. Impact of Energy Loss Coefficient on Left Ventricular Mass Regression in 
Patients Undergoing Aortic Valve Replacement: Preliminary Findings. : J Am Soc 
Echocardiogr. 2009 Mar 21 
 
11. Hilker L, Wodny M, Ginesta M, Wollert HG, Eckel L. Differences in the recovery of 
platelet counts after biological aortic valve replacement. Interact Cardiovasc Thorac 
Surg. 2009 Jan;8(1):70-3. Epub 2008 Oct 8 
 
12. Kubota S, Wakasa S, Ooka T, Tachibana T, Shiiya N, Matsui Y. A case of Carpentier-
Edwards pericardial bioprosthesis in mitral position explanted 22 years after 
implantation.  J Artif Organs. 2010 Apr;13(1):48-50. Epub 2010 Feb 17. 
 
13. Thalmann M, Gorlitzer M, Grabenwöger M, Moidl R. Commented on: World's first 
implant of a 23-mm Carpentier-Edwards Perimount Magna mitral bioprosthesis. 
 J Heart Valve Dis. 2009 May;18(3):352-3. 
 
14. Alsoufi B, Manlhiot C, McCrindle BW, Canver CC, Sallehuddin A, Al-Oufi S, Joufan M, 
Al-Halees Z. Aortic and mitral valve replacement in children: is there any role for 
biologic and bioprosthetic substitutes? Eur J Cardiothorac Surg. 2009 Jul;36(1):84-90; 
discussion 90. Epub 2009 Apr 14. 
 
 
 
Appendix 9: Page 32 of 32