Surgical Treatment of Aortic Stenosis With a Next Generation Surgical Aortic Valve
Phase: NA
Conditions: Aortic Valve Stenosis With Insufficiency, Aortic Valve Stenosis
Sponsor: Edwards Lifesciences

Edwards Lifesciences LLC 
One Edwards Way  Irvine, CA USA  92614 
Phone: 949.250.2500  Fax: 949.250.2525  www.edwards.com 
TRITON Trial 
Surgical Treatment of Aortic Stenosis With a Next 
Generation Surgical Aortic Valve (TRITON)  
NCT01445171
 September 15, 2011 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 1 of 54 
 
TRITON 
Surgical Treatment of Aortic Stenosis with a Next Generation Surgical 
Aortic Valve
CLINICAL PROTOCOL 
(Clinical Investigational Plan) 
Clinical Investigation Number: 2009-01 
Revision: E 
Effective Date: September 15, 2011 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 2 of 54 
 
 
TRITON 
Surgical Treatment of Aortic Stenosis with a Next Generation Surgical 
Aortic Valve
CLINICAL PROTOCOL 
(Clinical Investigational Plan) 
Clinical Investigation Number: 2009-01 
Revision: E 
Effective Date: September 15, 2011 
Protocol Change Status 
Protocol Revision # 
Revision Date 
Revision A 
September 14, 2009 
Revision B 
December 17, 2009 
Revision C 
April 22, 2010 
Revision D 
April 04, 2011 
Revision E 
September 15, 2011 
Investigation Sponsor: 
Edwards Lifesciences LLC 
One Edwards Way 
Irvine, CA 92614 USA 
CONFIDENTIAL AND PROPRIETARY DATA: This document and the information contained herein may not 
be reproduced, used or disclosed without written permission from Edwards Lifesciences LLC 
Edwards Lifesciences, Edwards, the stylized E logo, Ascendra, Carpentier-Edwards, EDWARDS INTUITY, Magna Ease, PERIMOUNT, 
PERIMOUNT Magna, Sapien, and Thermafix are trademarks of Edwards Lifesciences Corporation. 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 3 of 54 
 
 
TRITON 
Surgical Treatment of Aortic Stenosis with a Next Generation Surgical 
Aortic Valve
CLINICAL PROTOCOL 
(Clinical Investigational Plan) 
Clinical Investigation Number: 2009-01 
Revision: E 
Effective Date: September 15, 2011 
Signatures 
Study Principal Investigator: 
________________________________________ 
_______________ 
Sponsor: 
________________________________________ 
_______________ 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 4 of 54 
 
 
Table of Contents 
1 
SYNOPSIS ...................................................................................................................................... 7 
2 
INTRODUCTION .......................................................................................................................... 12 
2.1 
BACKGROUND ................................................................................................................................... 12 
2.2 
PURPOSE ......................................................................................................................................... 12 
2.2.1 
Hypothesis .......................................................................................................................... 12 
2.3 
DEVICES .......................................................................................................................................... 13 
2.3.1 
Bioprostheses ...................................................................................................................... 13 
2.3.2 
Delivery systems ................................................................................................................. 14 
2.3.3 
Ancillary products ............................................................................................................... 16 
2.3.4 
Intended use ....................................................................................................................... 17 
2.3.5 
Prior testing ........................................................................................................................ 17 
2.3.6 
Prior clinical studies ............................................................................................................ 17 
3 
RISK ANALYSIS ............................................................................................................................ 17 
3.1 
RISKS .............................................................................................................................................. 17 
3.2 
BENEFITS ......................................................................................................................................... 19 
3.3 
JUSTIFICATION .................................................................................................................................. 19 
4 
CLINICAL INVESTIGATION DESIGN ............................................................................................... 21 
4.1 
PHASE I ........................................................................................................................................... 21 
4.2 
PHASE II .......................................................................................................................................... 21 
5 
ENDPOINTS ................................................................................................................................. 21 
5.1 
SAFETY ENDPOINTS ............................................................................................................................ 21 
5.2 
PERFORMANCE ENDPOINTS ................................................................................................................. 22 
5.3 
OTHER DATA .................................................................................................................................. 22 
6 
SUBJECT POPULATION ................................................................................................................ 22 
6.1 
DEMOGRAPHIC AND CLINICAL CHARACTERISTICS ...................................................................................... 22 
6.2 
PRE-OPERATIVE CRITERIA .................................................................................................................... 22 
6.2.1 
Inclusion criteria ................................................................................................................. 22 
6.2.2 
Exclusion criteria ................................................................................................................. 23 
6.3 
INTRA-OPERATIVE CRITERIA ................................................................................................................. 24 
6.3.1 
Exclusion criteria ................................................................................................................. 24 
6.4 
WITHDRAWAL CRITERIA AND PROCEDURES ............................................................................................. 25 
7 
INVESTIGATIONAL DEVICE MANAGEMENT ................................................................................. 25 
7.1 
DEVICE SHIPMENTS ............................................................................................................................ 25 
7.2 
INVENTORY AND ACCOUNTABILITY RECORDS ........................................................................................... 25 
7.3 
DEVICE STORAGE ............................................................................................................................... 26 
7.4 
DEVICE RETURN ................................................................................................................................ 26 
8 
TRAINING ................................................................................................................................... 26 
8.1 
TRAINING OF INVESTIGATIONAL CENTER PERSONNEL ................................................................................. 26 
8.2 
DEVICES .......................................................................................................................................... 26 
8.3 
ECHOCARDIOGRAPHIC EXAMINATIONS ................................................................................................... 26 
8.4 
DOCUMENTATION ............................................................................................................................. 27 
9 
PROCEDURES AND METHODS ..................................................................................................... 27 
9.1 
BASELINE EVALUATION ....................................................................................................................... 27 
9.1.1 
Subject screening ................................................................................................................ 27 
9.1.2 
Informed consent ................................................................................................................ 27 
9.1.3 
Baseline assessment ........................................................................................................... 28 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 5 of 54 
 
 
9.2 
SURGICAL PROCEDURE........................................................................................................................ 29 
9.2.1 
Procedure preparation ........................................................................................................ 29 
9.2.2 
EDWARDS INTUITY Aortic Valve implanting procedure ...................................................... 29 
9.3 
SUBJECT ENROLLMENT ....................................................................................................................... 30 
9.4 
POST-PROCEDURE ............................................................................................................................. 30 
9.4.1 
Post-procedure care ............................................................................................................ 30 
9.4.2 
Discharge ............................................................................................................................ 30 
9.4.3 
Follow-up assessments ....................................................................................................... 31 
9.5 
ECHOCARDIOGRAM ........................................................................................................................... 33 
9.6 
DEVICE REMOVAL / EXPLANT PROCEDURE ............................................................................................... 33 
9.6.1 
Intra-operative removal ...................................................................................................... 33 
9.6.2 
Intra-operative or early post-operative explant ................................................................. 33 
9.6.3 
Late post-operative explant ................................................................................................ 34 
9.7 
MISSED SUBJECT VISITS....................................................................................................................... 34 
9.8 
INVESTIGATION SUBJECT EXIT ............................................................................................................... 34 
9.9 
CLINICAL INVESTIGATION TERMINATION ................................................................................................. 35 
10 
DATA COLLECTION AND REPORTING........................................................................................... 35 
10.1 
DATA COLLECTION METHODS .......................................................................................................... 35 
10.2 
SOURCE DOCUMENTATION REQUIREMENTS........................................................................................ 35 
10.3 
QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES ................................................................... 36 
11 
REPORTABLE EVENTS / EFFECTS .................................................................................................. 37 
11.1 
REPORTING PROCEDURE ................................................................................................................ 37 
11.2 
DEFINITIONS ................................................................................................................................ 37 
11.2.1 
Adverse event ................................................................................................................. 37 
11.2.2 
Adverse device effect ..................................................................................................... 37 
11.2.3 
Serious adverse event .................................................................................................... 37 
11.2.4 
Serious adverse device effect ......................................................................................... 38 
11.2.5 
Unanticipated Serious Adverse Device Effect (USADE) .................................................. 38 
11.3 
DEATHS AND EXPLANTS .................................................................................................................. 38 
11.3.1 
Subject deaths ................................................................................................................ 38 
11.3.2 
Device explants .............................................................................................................. 38 
12 
STATISTICAL ANALYSIS ................................................................................................................ 39 
12.1 
SAMPLE SIZE PHASE I .................................................................................................................... 39 
12.2 
SAMPLE SIZE PHASE II ................................................................................................................... 39 
12.3 
PHASE I ANALYSIS ......................................................................................................................... 39 
12.4 
PHASE II ANALYSIS ........................................................................................................................ 39 
12.4.1 
Analysis population ........................................................................................................ 39 
12.4.2 
Safety analysis ............................................................................................................... 40 
12.4.3 
Performance analysis ..................................................................................................... 40 
12.4.4 
Missing data .................................................................................................................. 40 
13 
MONITORING ............................................................................................................................. 41 
13.1 
MONITORING METHODS ................................................................................................................ 41 
13.2 
MONITORING PLAN ....................................................................................................................... 41 
13.3 
PROTOCOL DEVIATION ................................................................................................................... 42 
13.3.1 
Exceptions ...................................................................................................................... 42 
13.4 
COMMUNICATION PROCEDURES ...................................................................................................... 43 
14 
COMMITTEES .............................................................................................................................. 43 
14.1 
DATA MONITORING COMMITTEE .................................................................................................... 43 
14.2 
CLINICAL EVENTS COMMITTEE ........................................................................................................ 43 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 6 of 54 
 
 
15 
ETHICAL AND REGULATORY CONSIDERATIONS ........................................................................... 44 
15.1 
APPLICABLE REGULATIONS AND GUIDELINES ....................................................................................... 44 
15.2 
IMPROPER INFLUENCE ................................................................................................................... 44 
15.3 
DATA PROTECTION AND SUBJECT CONFIDENTIALITY ............................................................................. 44 
15.4 
INFORMED CONSENT AND REVIEW COMMITTEES ................................................................................. 45 
15.5 
INVESTIGATOR RESPONSIBILITIES ...................................................................................................... 45 
15.5.1 
General duties ................................................................................................................ 45 
15.5.2 
Investigator records ....................................................................................................... 45 
15.5.3 
Investigator reports ....................................................................................................... 46 
15.6 
INVESTIGATION SPONSOR RESPONSIBILITIES ....................................................................................... 46 
15.6.1 
General duties ................................................................................................................ 46 
15.6.2 
Selection of investigators ............................................................................................... 46 
15.6.3 
Monitoring the clinical investigation ............................................................................. 46 
15.6.4 
Sponsor records .............................................................................................................. 47 
15.6.5 
Sponsor reports .............................................................................................................. 47 
15.7 
MODIFICATIONS ........................................................................................................................... 47 
15.8 
CLINICAL INVESTIGATION COMPLETION OR TERMINATION AND CLOSE-OUT ............................................... 48 
15.9 
AUDITS AND INSPECTIONS .............................................................................................................. 48 
15.10 
PUBLICATION POLICY ..................................................................................................................... 48 
16 
REFERENCES................................................................................................................................ 49 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 7 of 54 
 
 
1 SYNOPSIS 
Investigation 
Number: 
2009-01 
Title: 
TRITON 
Surgical Treatment of Aortic Stenosis with a Next Generation
Investigation 
Sponsor: 
 Surgical 
Aortic Valve  
Edwards Lifesciences LLC 
One Edwards Way,  
Irvine, CA 92614 USA 
Principal 
Investigator1: 
Investigation 
Purpose: 
The purpose of this clinical investigation is to confirm that the safety and 
performance of the EDWARDS INTUITY Valve System, INTUITY Aortic 
Valve Models 8300ACA and 8300ACB used with the INTUITY Delivery 
System Models 8300DCA and 8300DCB respectively, are not adversely 
affected by the addition of a balloon expandable frame.  
Data collected in this clinical investigation will include short-term safety 
and performance of the device deployment and delivery systems as well 
as long-term clinical outcomes comparable to the other currently 
marketed aortic bioprosthesis.  Results of this clinical investigation will 
be used to support a CE Marking application in Europe and other global 
product registrations. 
Investigation 
Devices: 
The following two models are included in the study. 
Edwards INTUITY Valve System: 
INTUITY 
Aortic 
Valve, 
Model 
8300ACA  
and 
INTUITY Delivery System, Model 
8300DCA 
EDWARDS INTUITY Valve System: 
INTUITY 
Aortic 
Valve, 
Model 
8300ACB  
and 
INTUITY Delivery System, Model 
8300DCB 
7
1 Refer to the “List of Investigation Centers” for a complete list of Principal Investigators. 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 8 of 54 
 
 
Intended Use 
The devices together (EDWARDS INTUITY Aortic Valves and Delivery 
Systems) are intended for use in subjects with aortic stenosis or 
stenosis-insufficiency requiring primary replacement of the native aortic 
valve. 
Investigation 
Design: 
This is a two-phase, non-randomized, prospective, single arm, multi-
center clinical investigation. 
In Phase I, a total of 10 subjects will be enrolled at up to 2 participating 
investigational centers. Safety data will be reviewed by the Data 
Monitoring Committee (DMC) after 10 subjects have completed 1-
month follow-up.2
4.1
 Following recommendation by the DMC, enrollment 
will proceed to Phase II. (Section 
) 
In Phase II, 340 additional subjects will be enrolled in up to 8 
participating investigational centers. Combined enrollment in Phase I 
and Phase II of this investigation will be 350 subjects. 
Each subject in Phase I and Phase II is consented for a period of 5 years. 
All subjects will be assessed for clinical follow-up at the following 
intervals: Discharge, 1 month, 3 months, 1 year and annually thereafter 
until 5 years of follow-up is achieved per subject. (Section 4.2) 
Population: 
Adult male and female subjects diagnosed with aortic stenosis or 
stenosis-insufficiency requiring replacement of the native aortic valve. 
Enrollment 
Criteria: 
Pre-operative criteria 
Inclusion Criteria 
1.
Subject is 18 years or older
2.
Subject has aortic stenosis or stenosis-insufficiency of an aortic
valve requiring a planned replacement as indicated in the
preoperative evaluation.
3.
Subject is scheduled to undergo planned aortic valve replacement
with or without concomitant coronary bypass surgery, MAZE
procedure, septal myectomy, pacemaker/ICD implant and or atrial
appendage occlusion/removal.
4.
Subject has signed and dated the investigation informed consent
form prior to investigation procedures.
5.
Subject is geographically stable and agrees to attend follow-up
assessments at the hospital of surgical services for a maximum of
5 years.
Exclusion Criteria 
1.
Subject with pure aortic insufficiency.
2.
Subject requires emergency surgery.
3.
Subject with an aneurysm of the aortic root and / or ascending
aorta requiring surgical intervention).
4.
Subject with a left ventricular ejection fraction of ≤ 25%
8
2 This may include subjects who expired or had the valve explanted prior to 1 month. 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 9 of 54 
 
 
5.
Subject with a congenital bicuspid or unicuspid aortic valve.
6.
Subject had active endocarditis within 3 months prior to the
scheduled aortic valve replacement surgery.
7.
Subject with concomitant valve (mitral, tricuspid, or pulmonic)
disease requiring repair with an annuloplasty ring or replacement
with prosthesis.
8.
Subject had prior mitral, tricuspid or pulmonic valve surgery,
which included implantation of a bioprosthetic valve, mechanical
valve, or annuloplasty ring that will remain in situ.
9.
Subject had a myocardial infarction within 1 month prior to the
scheduled aortic valve replacement surgery.
10. Subject has a disease limiting life expectancy to less than 12
months.
11. Subject was previously implanted with EDWARDS INTUITY Aortic
Valve3
12. Subject is an alcohol and/or drug abuser.
.
13. Female subject is pregnant or lactating.
14. Subject is currently participating in another drug or device clinical
investigation.
15. Subject with documented leukopenia (WBC < 3.5x 103/µL), acute
anemia (Hgb < 10.0 gm/dL or < 6.2 mmol/L), thrombocytopenia
(platelet count < 100x 103/mL), or history of bleeding diathesis or
coagulopathy4
16. Subject who requires a non-cardiac procedure such as carotid
procedures or mediastinal tumor removal.
.
17. Subject had a stroke or transient ischemic attack within six months
prior to scheduled aortic valve replacement surgery.
18. Study site pre-operative echocardiograpic assessment shows
evidence of an intracardiac mass, thrombus, or vegetation.
19. Subject has hemodynamic or respiratory instability requiring
inotropic support, mechanical circulatory support, or mechanical
ventilation within 30 days of procedure.
20. Subject with documented renal insufficiency as determined by
Serum creatinine ≥ 200 µmol/L (2.27 mg/dL) at screening or end-
stage renal disease requiring chronic dialysis.
21. Subject with documented hyperparathyroidism.
Intra-operative criteria 
Exclusion Criteria 
1.
Participation in the clinical investigation may be contrary to the
subject’s medical treatment;
9
3 Previously implanted means that the EDWARDS INTUITY Aortic Valve implant procedure was 
completed.  The INTUITY Aortic Valve procedure is complete when the surgeon takes the patient off 
cardiopulmonary bypass and restarts the heart 
4 WBC: White Blood Cells; Hgb: Hemoglobin 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 10 of 54 
 
 
2.
Any anatomical findings that would not be suitable for
implantation of the EDWARDS INTUITY Aortic Valve or use of the
EDWARDS INTUITY Delivery System and which are discovered,
intraoperatively. These may include findings such as:
a.
Significant calcium on the anterior mitral leaflet which
cannot be removed,
b.
Septal hypertrophy that will not be corrected by
myectomy, or pronounced septal calcification,
c.
The position of the coronary ostia relative to the
EDWARDS INTUITY Aortic Valve Models 8300ACA
and/or 8300ACB would result in obstruction of blood
flow,
d.
Extensive calcification of the aortic root,
e.
Left atrial thrombus,
f.
The subject is hemodynamically unstable during the
procedure requiring the procedure to be aborted prior
to insertion of the investigational bioprosthesis and
delivery system,
g.
A device is not available in the correct size for the
subject,
h.
Annular deformation which may or may not be caused
by too extensive decalcification of the aortic annulus;
3.
It is discovered that the subject is participating in a clinical
investigation of another drug or device prior to insertion of the
investigational bioprosthesis and delivery system
Safety Endpoints: 
The following primary safety endpoints will be assessed throughout 
each subject’s participation in the investigation:  

Study valve-related mortality

Thromboembolic events

Study valve thrombosis

Major bleeding events

Study valve paravalvular leakage

Study valve-related endocarditis
In addition, the following safety endpoints will also be assessed 
throughout each subject’s participation in the investigation:  

All-cause mortality

Study valve structural valve deterioration

Hemolysis

Study valve-related reoperation

Study valve explant

All adverse events

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 11 of 54 
 
 
Performance 
Endpoints: 
The following performance endpoint will be assessed when the 
investigation procedure is performed: 

Device technical success (successful delivery and deployment of
one bioprosthesis with one delivery system)
The following performance endpoint will be determined when the 
subject is discharged from the hospital or 10 days post implant, 
whichever occurs first: 

Procedure success defined as device technical success followed
by the absence of adverse events requiring device reoperation,
requiring implantation of permanent pacemaker (with baseline
sinus rhythm and no other conduction issues), or subject death
The following performance endpoints will be assessed at each scheduled 
follow-up visit:  

Improvement in NYHA functional class

Hemodynamic performance (mean gradient, effective orifice
area, regurgitation by echocardiogram)
Other data: 
The following data also will be collected: 

EQ-5D Quality of Life questionnaire (baseline and 1 year only)

Blood data (White Blood Cell Count, Red Blood Cell Count,
Hemoglobin, Hematocrit, Haptoglobin, Reticulocytes, Platelet
Count, Serum Lactate Dehydrogenase)

New onset or worsening of conduction disturbances
Investigation 
Committees: 
Data Monitoring Committee 
Clinical Events Committee 
Echocardiography 
Core Lab: 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 12 of 54 
 
 
2 INTRODUCTION 
2.1 
BACKGROUND 
Aortic Valve Replacement (AVR) surgery is considered to be a class I indication for 
symptomatic patients with severe calcific AS. Braunwald advocates AVR surgery as the 
treatment of choice in most adults with calcific AS. The aortic valve should be replaced 
in symptomatic patients with hemodynamic evidence of severe aortic obstruction. The 
same applies to asymptomatic patients with progressive left ventricular dysfunction 
and/or significant ventricular ectopic activity at rest, or an abnormal hemodynamic 
response (inadequate elevation of systolic arterial pressure) to exercise [13].  Apart 
from symptomatic relief, the operation improves long-term survival. In one series, 
three-year survival was 87% in operated and 21% in non-operated patients [54]. 
Traditionally aortic valve replacement surgery is performed via a full sternotomy. 
However with the introduction of minimally invasive aortic valve surgery in 1996 [1, 2] 
this surgical approach is gaining in acceptance. Many studies show that it can be done 
safely with mortality and morbidity similar to conventional full sternotomy aortic valve 
surgery [3—15]. Several studies also show that the minimal access approach 
contributes to better surgical outcomes compared to a full sternotomy [3—5, 14—16] 
although this is still controversial. Published studies show that minimal access 
approaches have shorter length of stay [3—5, 15, 16], more home discharge [3—5, 15], 
less incisional pain [6, 20], shorter duration of ventilation [4—6], less blood loss [4—6, 
11, 16] and less blood transfusion [5], compared to a full sternotomy.  Advances in 
technology are designed to facilitate minimally invasive aortic valve surgical techniques 
and reduce the risks associated with longer pump and coagulation times.  One of these 
advances is the Model 8300TFX bioprosthesis.   
2.2 
PURPOSE 
The purpose of this clinical investigation is to confirm that the safety and performance 
of the EDWARDS INTUITY Valve System, INTUITY Aortic Valve Models 8300ACA and 
8399ACB, respectively used with the EDWARDS INTUITY Valve System, INTUITY Delivery 
System Models 8300DCA and 8300DCB are not adversely affected by the addition of a 
balloon expandable frame.  
Data collected in this clinical investigation will include short-term safety and 
performance of the devices deployment and delivery systems as well as long-term 
clinical outcomes comparable to the other currently marketed aortic bioprosthesis. 
Results of this clinical investigation will be used to support a CE Marking application in 
Europe and other global product registrations. 
2.2.1 HYPOTHESIS 
Success of this investigation will be determined at each phase of the investigation: 
 
Phase I will be considered successful when the Data Monitoring Committee 
(DMC) (Section 14.1) determines that the investigation can proceed to 
enrollment in Phase II 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 13 of 54 
 
 
 
Phase II will be considered successful when the DMC reviews 3 month data and 
determines that use of the EDWARDS INTUITY Aortic Valve and the EDWARDS 
INTUITY Delivery System is clinically safe. 
2.3 
DEVICES 
2.3.1 BIOPROSTHESES 
The EDWARDS INTUITY Valve System, INTUITY Aortic Valve Models 8300ACA and 
8300ACB (also referred to as EDWARDS INTUITY Aortic Valve) is a stented trileaflet 
bioprosthesis comprised of bovine pericardium that has been preserved in a buffered 
glutaraldehyde solution and mounted on a balloon expandable frame. It is available in 
sizes 19, 21, 23, 25, and 27 mm. To facilitate implantation in subjects with small aortic 
roots, the EDWARDS INTUITY Aortic Valve has a low supra-annular profile height. 
Figure 1: EDWARDS INTUITY Aortic Valve Model 
8300ACA 
Figure 2: EDWARDS INTUITY Aortic Valve Model 
8300ACB 
Both Models 8300ACA and 8300ACB are treated with the Carpentier-Edwards 
ThermaFix process, which involves heat treatment of the tissue in glutaraldehyde and 
uses ethanol and polysorbate-80 (a surfactant). The bioprosthesis is packaged and 
terminally sterilized in glutaraldehyde. Glutaraldehyde is shown to both reduce the 
antigenicity of tissue xenograft bioprostheses and increase tissue stability.  
The wireform is designed to be compliant at the orifice as well as at the commissures. 
The compliance of the commissure supports is intended to reduce the loading shock at 
the valve commissures and free margin of the leaflets. The compliance of the orifice is 
intended to reduce the stress on the leaflets. The compliant orifice concept is based on 
the physiology and mechanics of natural heart valves and reported experience with 
implantation of unstented homografts. 
The wireform is made of cobalt-chromium alloy, a corrosion-resistant alloy, chosen 
because of its superior spring efficiency and fatigue-resistant characteristics, and is 
covered with a woven polyester fabric. A thin, cobalt-chromium alloy/polyester film 
laminate band surrounds the base of the wireform providing structural support for the 
orifice.  

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 14 of 54 
 
 
A soft, silicone-rubber sewing ring, which is covered with a porous, seamless 
polytetrafluoroethylene (PTFE) cloth to facilitate tissue ingrowth and encapsulation, is 
attached to the wireform. The sewing ring is scalloped to conform to the natural aortic 
annulus. The compliant nature of the sewing ring facilitates coaptation between the 
bioprosthesis and an often irregular or calcific tissue bed. The sewing ring has three, 
equally spaced suture markers at the cusp centers to aid in bioprosthesis orientation 
and suture placement. 
The balloon expandable frame is made of stainless steel and is attached to the inflow 
aspect of the bioprosthesis. In the EDWARDS INTUITY Aortic Valve Model 8300ACA the 
balloon expandable frame is covered with a knitted PTFE cloth and a layer of polyester 
cloth covering the external outflow end of the balloon expandable frame. In the 
EDWARDS INTUITY Aortic Valve Model 8300ACB the knitted PTFE cloth covering the 
balloon expandable frame is folded over to the distal end of the frame. The purpose of 
the cloth frame coverage is to help prevent paravalvular leaks.  
An integral bioprosthesis holder is attached to the bioprosthesis by means of sutures 
to facilitate handling, deployment, and suturing the bioprosthesis during implantation. 
The holder is easily detached by the surgeon. In the EDWARDS INTUITY Aortic Valve 
Model 8300ACA the holder is mounted on the commissure posts; in Model 8300ACB 
the holder is mounted on the cusps nadir. 
Please refer to the EDWARDS INTUITY Valve System, Aortic Valve Models 8300ACA and 
8300ACB Instruction for Use for further details. 
2.3.2 DELIVERY SYSTEMS 
The EDWARDS INTUITY Delivery System Models 8300DCA and 8300DCB are used with 
the EDWARDS INTUITY Aortic Valve Models 8300ACA and 8300ACB respectively. They 
are not interchangeable. 
The EDWARDS INTUITY Delivery System Model 8300DCA consists of the following 
components: (see Figure 3) 
Figure 3: EDWARDS INTUITY delivery system model 8300DCA 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 15 of 54 
 
 
•
Introducer
•
Insertion Tool
•
Distal Handle
•
Balloon Catheter / Proximal Handle with Y-connector
The assembled Balloon Introducer and Insertion tool is used to remove the EDWARDS 
INTUITY Aortic Valve Model 8300ACA from the packaging jar and to enable connection 
of the distal handle to the proximal threaded section of the balloon introducer that 
extends beyond the valve holder. This assembly facilitates removal of the packaging 
sleeve from the bioprosthesis. Upon removal of the sleeve, the insertion tool is 
removed from the balloon introducer and the distal handle/bioprosthesis assembly is 
ready for deployment.  
The Distal Handle is used to hold the bioprosthesis while the nadir sutures are placed 
through the sewing ring and to facilitate parachuting the implant down into the native 
valve annulus.  When connected to the Proximal Handle, the Distal Handle also 
controls the position of the expanding balloon with regard to the bioprosthesis. 
The Balloon Catheter / Proximal Handle with Y-connector is connected to the Distal 
Handle and used to expand the EDWARDS INTUITY Aortic Valve expandable frame by 
using an inflation device. The Balloon Catheter/Proximal Handle with Y-connector (in 
the figure above) is a coaxial-designed catheter with a distal inflatable balloon. At the 
proximal end of the catheter, there is a standard Y-connector with an inflation port 
(marked “BALLOON”) used for balloon inflation. The balloon is inflated by injecting a 
saline solution through the luer port (marked “BALLOON”) on the Y connector. An 
inflation device filled with saline solution is connected to the inflation port to 
pressurize and expand the balloon. 
A delivery system is available for each size of the EDWARDS INTUITY Aortic Valve 
Model 8300ACA (19, 21, 23, 25 and 27 mm). 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 16 of 54 
 
 
The EDWARDS INTUITY delivery system model 8300DCB consists of the following 
components (see Figure 4): 
Figure 4: EDWARDS INTUITY delivery system model 8300DCB & 
Atrion Inflation Device, QL2540 – Model 96417 
The EDWARDS INTUITY delivery system model 8300DCB is designed to introduce the 
model 8300ACB valve to the surgical site after removal of the diseased native leaflets. 
The delivery system includes an integrated balloon catheter and tubular handle shaft 
through which the catheter extends.  The distal end of the handle shaft includes an 
adapter, which mates with the holder of the valve, and a locking sleeve for rapidly 
connecting the delivery system to the valve holder.  The balloon portion of the delivery 
system resides within the adapter, and advances distally into position for expanding 
the inflow frame.  A tubular balloon introducer sleeve attached when removing the 
valve from a storage jar facilitates passage of the balloon through the valve. 
A size-specific delivery system is available for each size of the EDWARDS INTUITY Aortic 
Valve Model 8300ACB (19, 21, 23, 25 and 27 mm). 
Please refer to the EDWARDS INTUITY Valve System, Delivery System Models 8300DCA 
and 8300DCB Instruction for Use for further details. 
2.3.3 ANCILLARY PRODUCTS 
The Carpentier-Edwards aortic sizers, model 1133 are used to size the native annulus 
determining the appropriate bioprosthesis size (EDWARDS INTUITY Aortic Valve Model 
8300ACA and Model 8300ACB). Model 1133 sizers are fabricated from translucent 
Polysulfone plastic to permit direct observation of their fit within the annulus. Each 
sizer consists of a handle with a different sizing configuration at each end. On one side 
of the handle is a cylindrical end with an integrated lip that reflects the bioprosthesis 
sewing ring geometry. On the other side of the handle is a bioprosthesis replica end 
that reflects the bioprosthesis sewing ring geometry as well as the height and location 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 17 of 54 
 
 
of the stent posts. A sizer is available for each size of the aortic bioprosthesis (19, 21, 
23, 25 and 27 mm). 
2.3.4 INTENDED USE 
The EDWARDS INTUITY Valve System, INTUITY Aortic Valve Models 8300ACA and 
8300ACB and INTUITY Delivery System Models 8300DCA and 8300DCB are intended to 
be used in subjects with aortic stenosis or stenosis-insufficiency who require 
replacement of their native aortic valve. 
Refer to the Instructions for Use in the Clinical Investigator’s Brochure (CIB) for 
contraindications, procedure steps, and cautions. 
2.3.5 PRIOR TESTING 
A Clinical Investigator’s Brochure (CIB) has been prepared for both the EDWARDS 
INTUITY Aortic Valve and the EDWARDS INTUITY Delivery System. The CIB includes the 
non-clinical testing results for the Magna Ease, the valved component of the EDWARDS 
INTUITY Aortic Valve.  
2.3.6 PRIOR CLINICAL STUDIES 
No prior clinical studies have been conducted for the EDWARDS INTUITY Aortic Valve 
or the EDWARDS INTUITY Delivery System.  
A summary of prior clinical studies on similar pericardial valves, the Carpentier-
Edwards PERIMOUNT Aortic bioprosthesis (model 2700) and the Carpentier-Edwards 
PERIMOUNT Magna Aortic bioprosthesis (model 3000/3000TFX) are included in the 
Clinical Investigator’s Brochure. 
3 RISK ANALYSIS 
3.1 
RISKS 
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 subject reaction to an implanted device, or to physical or chemical changes 
in the components, particularly those of biological origin, may occur at varying 
intervals (hours or days) necessitating reoperation and replacement of the prosthetic 
device 
Known risks associated with the use of stented bioprosthetic heart valves include: 
•
Stenosis
•
Regurgitation through an incompetent valve
•
Perivalvular leak
•
Endocarditis
•
Hemolysis
•
Thromboembolism
•
Thrombotic obstruction
•
Bleeding diatheses related to the use of anticoagulant therapy

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 18 of 54 
 
 
•
Malfunctions of the valve due to distortion at implant, fracture of the cobalt
chromium alloy 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
Potential risks associated with the use of stented bioprosthetic heart valves include: 
•
Angina
•
Cardiac arrhythmias
•
Heart failure
•
Hemolysis
•
Hemolytic anemia
•
Hemorrhage
•
Myocardial infarction
•
Prosthesis leaflet entrapment
(impingement)
•
Prosthesis nonstructural
dysfunction
• Prosthesis pannus
• Prosthesis perivalvular leak
• Prosthesis regurgitation
• Prosthesis structural deterioration
• Prosthesis thrombosis
• Prosthesis frame malformation (from
chest compression or trauma)
• Prosthesis transvalvular leak
• Stroke
• Transient Ischemic Attack (TIA)
Potential risks associated with aortic valve replacement surgery include: 
•
Procedural bleeding
•
Post-procedural bleeding
•
Anticoagulant related bleeding
•
Disseminated Intravascular
Coagulation (DIC)
•
Heparin Induced
Thrombocytopenia (HITs)
•
Hematoma
•
Pericardial Tamponade
•
Annular Dissection/Tear
•
Aortic Dissection/Tear
•
Arterial Dissection
•
Cardiac Arrest
•
Cardiogenic Shock
•
Heart Failure
•
Hypotension
•
Hypertension
• Pericardial Effusion
• Perforation of free myocardial wall
• Myocardial Infarction
• Peripheral Embolic Event
• Pulmonary Embolism
• Esophageal rupture
• Bacteremia
• Pneumonia
• Sepsis/Septicemia
• Sternal Wound Infection
• Infection, local
• Infection, systemic
• Vascular Access Site Complication
• Deep Vein Thrombosis (DVT)
• Allergic reaction
• Pleural effusion
Potential Risks associated with EDWARDS INTUITY Aortic Valves and Delivery Systems 
may be found in the respective IFU. Based on a review of scientific literature, 
preliminary animal studies, risk analysis and a Failure Modes and Effects Analysis 
(FMEA) potential risks associated with the use of the EDWARDS INTUITY Aortic Valves 
may include: 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 19 of 54 
 
 
•
Loss of frame structural integrity resulting in damage to aortic wall or aortic
annulus
•
Delivery system impingement resulting in mitral chordae trauma or damage
•
Frame damage or flaring resulting in a reduction of effective orifice area
•
Hemolysis
•
Frame expansion resulting in conduction interruptions or disturbances (i.e.
arrhythmia)
•
Frame expansion resulting in mitral valve impingement or abrasion with or
without mitral regurgitation
•
Insufficient frame expansion/suturing resulting in paravalvular leak requiring
intervention or reoperation to resolve
•
Device malpositioning resulting in ostial blockage
•
Device embolization into the aorta/ ventricular due to suture failure
Some or all of these risks could require a need for reoperation or explant, and may 
lead to permanent disability or death. 
There may be other risks that are unknown at this time. All safety events will be 
collected and reviewed throughout the entire investigation and follow-up period. 
Investigators will be notified of any additional risks identified that could affect the 
health, safety or welfare of the investigation subjects. 
3.2 
BENEFITS 
There are no guaranteed benefits from participation in this clinical investigation.  
Aortic valve replacement with the EDWARDS INTUITY Aortic Valve may result in one or 
more of the following benefits: improved valvular function, acute alleviation of 
symptoms related to aortic stenosis, and/or improved morbidity and mortality. 
Additionally, information gained from the conduct of this investigation may be of 
benefit to other people with the same medical condition in the future. The long-term 
results of using the investigation valve are not known at the present time. Alternative 
treatments may include palliative medical therapy, aortic balloon valvuloplasty and 
replacement of the aortic valve with prosthesis other than the EDWARDS INTUITY 
Aortic Valve.  
3.3 
JUSTIFICATION 
Aortic stenosis is progressive degenerative disease that decreases systemic and 
coronary blood flow, valvular and ventricular function. Many patients are 
asymptomatic until the disease is well-advanced and once diagnosed have a poor 
prognosis (onset of symptoms to the time of death of approximately two years in 
patients with heart failure, three years in those with syncope, and five years in those 
with angina [31]). Other studies have reported that among symptomatic patients with 
medically treated moderate-to-severe AS, mortality rates after the onset of symptoms 
were approximately 25% at one year and 50% at two years.  
Aortic Valve Replacement (AVR) surgery is the current procedure of choice for 
symptomatic adult patients with severe calcific AS, symptomatic patients with 
evidence of severe aortic obstruction, progressive left ventricular dysfunction, 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 20 of 54 
 
 
ventricular ectopy at rest, or an abnormal hemodynamic response when exercising. 
One series reported that patients undergoing AVR had improved long-term survival 
rate, with a three-year rate of 87% in operated patients versus a 21% rate in non-
operated patients [54]. 
At most centers, the reported operative mortality rate for AVR procedures ranges from 
2 to 8% [4, 54, 61] increasing in patients over 70 years of age, and up to 30% , patients 
80 years or older, or patients presenting in advanced heart failure with left ventricular 
dysfunction. Despite the poor outcomes reported for these severely compromised 
patients, AVR surgery still appears to have a survival benefit in patients with early 
diagnoses and surgical intervention compared medical therapy or no intervention [25, 
48]. 
Since the risks associated with use of the EDWARDS INTUITY Aortic Valve are expected 
to be similar in nature and rate to those of other aortic bioprostheses, the Sponsor 
considers the risk of use of EDWARDS INTUITY Valve System to outweigh the risks of 
medical therapy or no surgical intervention in the defined subject population. 
Over the past decade there is a trend towards less invasive medical procedures in 
virtually all medical specialties. Clinical outcome studies have now shown that less 
invasive procedures can provide reductions in procedure and hospitalization times, 
cost savings and improvements in subject recuperation and outcomes [73, 74].  
Edwards developed the EDWARDS INTUITY Valve System, INTUITY Aortic Valve Models 
8300ACA and 8300ACB to facilitate less invasive surgical approaches requiring fewer 
suture placements. 
The Models 8300ACA and 8300ACB valve use the commercially available Magna Ease 
valve with a modified balloon expandable annular frame. The Models 8300DCA and 
8300DCB delivery system allows for less invasive valve replacement. 
The potential advantage of the Models 8300ACA and 8300ACB design is a balloon 
expandable frame reducing the number of sutures required without increasing the risk 
for paravalvular leak. 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 21 of 54 
 
 
4 CLINICAL INVESTIGATION DESIGN 
This is a two-phase, non-randomized, prospective, single arm, multi-center clinical 
investigation.  
4.1 
PHASE I 
In Phase I, a total of 10 subjects will be enrolled at up to 2 participating investigational 
centers. Safety data will be reviewed by the Data Monitoring Committee (DMC) after 
10 subjects have completed 1-month follow-up5
14.1
. Following recommendation by the 
DMC, enrollment will proceed to Phase II. (Refer to Section 
 for DMC.) 
4.2 
PHASE II 
In Phase II, 340 additional subjects will be enrolled in up to 8 participating 
investigational centers. Combined enrollment in Phase I and Phase II of this 
investigation will be 350 subjects. 
Each subject in Phase I and Phase II is consented for a period of 5 years. All subjects 
will be assessed for clinical follow-up at the following intervals: Discharge, 1 month, 3 
months, 1 year and annually thereafter until 5 years of follow-up is achieved per 
subject. 
5 ENDPOINTS 
5.1 
SAFETY ENDPOINTS 
The following primary safety endpoints will be assessed throughout each subject’s 
participation in the investigation:  

Study valve-related mortality

Thromboembolic events

Study valve thrombosis

Major bleeding events

Study valve paravalvular leakage

Study valve-related endocarditis
In addition, the following safety endpoints will also be assessed throughout each 
subject’s participation in the investigation:  

All-cause mortality

Study valve structural valve deterioration

Hemolysis

Study valve-related reoperation

Study valve explant

All adverse events
21
5 This may include subjects who expired or had the valve explanted prior to 1 month. 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 22 of 54 
 
 
5.2 
PERFORMANCE ENDPOINTS 
The following performance endpoint will be assessed when the investigation 
procedure is performed: 

Device technical success (successful delivery and deployment of one
bioprosthesis with one delivery system)
The following performance endpoint will be determined when the subject is 
discharged from the hospital or 10 days post implant, whichever occurs first: 

Procedure success defined as device technical success followed by the absence
of adverse events requiring device reoperation, requiring implantation of
permanent pacemaker (with baseline sinus rhythm and no other conduction
issues), or subject death
The following performance endpoints will be assessed at each scheduled follow-up 
visit:  

Improvement in NYHA functional class

Hemodynamic 
performance 
(mean 
gradient, 
effective 
orifice 
area,
regurgitation by echocardiogram).
5.3 
OTHER DATA 
The following data also will be collected: 

EQ-5D Quality of Life questionnaire at baseline, 3-months and 1-year only,

Blood data (White Blood Cell Count, Red Blood Cell Count, Hemoglobin,
Hematocrit, Haptoglobin, Reticulocytes, Platelet Count, Serum Lactate
Dehydrogenase) at baseline, 3-months, 1- and 5-years only,

New onset or worsening of conduction disturbances.
6 SUBJECT POPULATION 
6.1 
DEMOGRAPHIC AND CLINICAL CHARACTERISTICS 
Adult male and female subjects diagnosed with aortic stenosis or stenosis-insufficiency 
and scheduled to undergo aortic valve replacement are eligible for participation in the 
clinical investigation. 
6.2 
PRE-OPERATIVE CRITERIA 
6.2.1 INCLUSION CRITERIA 
The principal investigator at the investigational center has the responsibility of 
screening potential subjects to determine if the subjects meet all the inclusion criteria. 
The following are requirements for entry into Phase I or Phase II of the clinical 
investigation:  
1. Subject is 18 years or older
2. Subject has aortic stenosis or stenosis-insufficiency of an aortic valve requiring
a planned replacement as indicated in the preoperative evaluation.

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 23 of 54 
 
 
3. Subject is scheduled to undergo planned aortic valve replacement with or
without concomitant coronary bypass surgery, MAZE procedure, septal
myectomy, pacemaker/ICD implant and or atrial appendage occlusion/removal.
4. Subject has signed and dated the investigation informed consent form prior to
investigation procedures.
5. Subject is geographically stable and agrees to attend follow-up assessments at
the hospital of surgical services for a maximum of 5 years.
6.2.2 EXCLUSION CRITERIA 
The principal investigator at the investigational center must exclude subjects if any of 
the exclusion criteria is present. The following are the criteria for exclusion from 
participating in Phase I or Phase II of the clinical investigation: 
1. Subject with pure aortic insufficiency.
2. Subject requires emergency surgery.
3. Subject with an aneurysm of the aortic root and / or ascending aorta requiring
surgical intervention).
4. Subject with a left ventricular ejection fraction of ≤ 25%.
5. Subject with a congenital bicuspid or unicuspid aortic valve.
6. Subject had active endocarditis within 3 months prior to the scheduled aortic
valve replacement surgery.
7. Subject with concomitant valve (mitral, tricuspid, or pulmonic) disease
requiring repair with an annuloplasty ring or replacement with prosthesis.
8. Subject had prior mitral, tricuspid or pulmonic valve surgery, which included
implantation of a bioprosthetic valve, mechanical valve, or annuloplasty ring
that will remain in situ.
9. Subject had a myocardial infarction within 1 month prior to the scheduled
aortic valve replacement surgery.
10. Subject has a disease limiting life expectancy to less than 12 months.
11. Subject was previously implanted with EDWARDS INTUITY Aortic Valve6
12. Subject is an alcohol and/or drug abuser.
. 
13. Female subject is pregnant or lactating.
14. Subject is currently participating in another drug or device clinical investigation.
15. Subject with documented leukopenia (WBC < 3.5x 103/µL), acute anemia (Hgb <
10.0 gm/dL or < 6.2 mmol/L), thrombocytopenia (platelet count < 100x
103/mL), or history of bleeding diathesis or coagulopathy 7
16. Subject who requires a non-cardiac procedure such as carotid procedures or
mediastinal tumor removal.
.
23
6 Previously implanted means that the EDWARDS INTUITY Aortic Valve implant procedure was 
completed.  The EDWARDS INTUITY Aortic Valve procedure is complete when the surgeon takes the 
patient off cardiopulmonary bypass and restarts the heart. 
7  WBC: White Blood Cells; Hgb: Hemoglobin 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 24 of 54 
 
 
17. Subject had a stroke or transient ischemic attack within six months prior to
scheduled aortic valve replacement surgery.
18. Study site pre-operative echocardiograpic assessment shows evidence of an
intracardiac mass, thrombus, or vegetation.
19. Subject has hemodynamic or respiratory instability requiring inotropic support,
mechanical circulatory support, or mechanical ventilation within 30 days of
procedure.
20. Subject with documented renal insufficiency as determined by Serum
creatinine ≥ 200 µmol/L (2.27 mg/dL) at screening or end-stage renal disease
requiring chronic dialysis.
21. Subject with documented hyperparathyroidism.
6.3 
INTRA-OPERATIVE CRITERIA 
6.3.1 EXCLUSION CRITERIA 
These exclusion criteria will be determined after subject consent, intraoperatively and 
before any attempt with an EDWARDS INTUITY valve is performed. 
The Investigator may exclude any subject due to any of the following conditions:  
1. Participation in the clinical investigation may be contrary to the subject’s
medical treatment;
2. Any anatomical findings that would not be suitable for implantation of the
EDWARDS INTUITY Aortic Valve or use of the EDWARDS INTUITY Delivery
System and which are discovered, intraoperatively. These may include findings
such as:
a. Significant calcium on the anterior mitral leaflet which cannot be
removed,
b. Septal hypertrophy that will not be corrected by myectomy, or
pronounced septal calcification,
c.
The position of the coronary ostia relative to the EDWARDS INTUITY
Aortic Valve Models 8300ACA and/or 8300ACB would result in
obstruction of blood flow,
d. Extensive calcification of the aortic root,
e. Left atrial thrombus,
f.
the subject is hemodynamically unstable during the procedure requiring
the procedure to be aborted prior to insertion of the investigational
bioprosthesis and delivery system,
g. A device is not available in the correct size for the subject,
h. Annular deformation which may or may not be caused by too extensive
decalcification of the aortic annulus;
3. It is discovered that the subject is participating in a clinical investigation of
another drug or device prior to insertion of the investigational bioprosthesis
and delivery system.
The Investigator will document the exclusion of investigation subjects and notify the 
Investigation Sponsor within 5 working days. Additional subjects will be screened to 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 25 of 54 
 
 
replace those subjects who are excluded by the Investigator during the surgical 
procedure prior to implantation. 
6.4 
WITHDRAWAL CRITERIA AND PROCEDURES 
Subjects may voluntarily withdraw consent at any time during Phase I or Phase II of the 
clinical investigation with no loss of benefit or penalty. Subjects will be exempt from 
follow-up after withdrawing from the clinical investigation. For subjects who are 
consented but have withdrawn, the investigational center must retain the subject’s 
informed consent and all documents pertaining to the subject prior to the subject’s 
withdrawal. Additional subjects will not be enrolled to replace those subjects 
implanted with the bioprosthesis who chose to withdraw from the clinical 
investigation. 
7 INVESTIGATIONAL DEVICE MANAGEMENT 
7.1 
DEVICE SHIPMENTS 
An initial set of EDWARDS INTUITY Aortic Valves and EDWARDS INTUITY Delivery 
Systems will be shipped to the investigational center once the following conditions are 
met: the investigational center has obtained Ethics Committee approval, a signed 
Clinical Investigational Agreement is in place, and the Site Initiation Visit, including 
Principal Investigator training, has been completed. Additional devices will be sent to 
the investigational center as devices are used or as needed. 
7.2 
INVENTORY AND ACCOUNTABILITY RECORDS  
All device shipments will have inventory and shipment records. Devices may be hand 
carried to participating investigational centers by Investigational Sponsor personnel 
and will be accompanied by delivery of investigational device documentation. The 
principal investigator(s) or designee will take inventory of the product and complete 
the delivery documentation with receipt date, condition of the device and signature. 
Both the investigational center and the Investigation Sponsor will retain copies of 
these documents. 
The investigator will maintain a Device Accountability Log of all investigational devices 
received for use during this clinical investigation. The log will be kept with the 
documents for the clinical investigation and will be available for review during 
Investigational Sponsor monitoring visits. Documentation on the log will include: 
1. Valve Model number
2. Valve serial number
3. Valve size
4. Delivery system Model number
5. Delivery system lot number
6. Delivery system size
7. Subject identification number for the clinical investigation, if device was used
or opened

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 26 of 54 
 
 
8. Date of use or if not used, date of return and Returned Goods Authorization
(RGA) number (if applicable), or date of discard8
7.3 
DEVICE STORAGE 
.
The device inventory will be stored in a locked, controlled, cool, dry and clean area as 
described in the Instructions for Use (IFU). This storage area shall be accessible only to 
the principal investigator(s), his/her co-investigator or approved designee. Only cardiac 
surgeons identified in the Clinical Investigational Agreement and the Delegation of 
Authority form on file at the Investigation Sponsor may use the investigational device. 
7.4 
DEVICE RETURN 
The principal investigator(s) will be notified in writing upon termination of the clinical 
investigation. All unused devices in original package and/or those in opened packages 
as well as those removed from the original package will be returned upon receipt of 
this notice. The Investigator’s copy of the Device Accountability log must document 
any unused devices that have been returned. In the event that the EDWARDS INTUITY 
Aortic Valve is removed from the package, the bioprosthesis should be placed in a 
container with a suitable histological fixative such as 10% formalin or 2% 
glutaraldehyde immediately and returned to the Investigation Sponsor. Refrigeration is 
not necessary under these circumstances. Contact Edwards the Investigation Sponsor 
for additional instructions. 
8 TRAINING 
8.1 
TRAINING OF INVESTIGATIONAL CENTER PERSONNEL 
Principal investigator(s) and support staff will be trained by the Investigation Sponsor 
on the use of the EDWARDS INTUITY Aortic Valve and the EDWARDS INTUITY Delivery 
System, the Protocol, the Clinical Investigator’s Brochure, electronic Case Report Forms 
(eCRF) and Electronic Data Capture (EDC) system, device accountability procedures, 
GCP (Good Clinical Practices) Guidelines and other investigation documents as 
applicable. A “Delegation of Authority Form” will be completed at each investigational 
center designating which individuals are allowed to perform specific clinical 
investigation related tasks. The delegated tasks will determine what the training 
requirements are for each member of the investigation support staff. 
8.2 
DEVICES 
Each cardiac surgeon participating in the clinical investigation must be trained on the 
use of the devices before screening potential subjects or using the EDWARDS INTUITY 
Aortic Valve and the EDWARDS INTUITY Delivery System.  
8.3 
ECHOCARDIOGRAPHIC EXAMINATIONS 
Each sonographer participating in the clinical investigation must be trained on the 
requirements of the Echo Manual. 
26
8 Bioprostheses must be returned to the Sponsor. It is preferable that delivery systems are returned 
also, but they may be discarded as described in the IFU. 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 27 of 54 
 
 
8.4 
DOCUMENTATION 
Training will be documented on a training record provided by the Investigation 
Sponsor, which the trainee must sign and date. The training of investigation support 
staff must be completed and documented before the staff member may perform the 
specific clinical investigation related tasks delegated to them by the Principal 
Investigator. 
9 PROCEDURES AND METHODS 
9.1 
BASELINE EVALUATION 
The Phase I or Phase II baseline evaluation will include: 
1.
Initial screening for the clinical inclusion and exclusion criteria,
2.
Informed consent discussion and dated signature
3.
History and physical examination,
4.
Baseline blood studies per protocol, Section 9.1.3
5.
Baseline transthoracic echocardiogram (TTE) per protocol (Section 9.5)
6.
Baseline 12 lead electrocardiogram
7.
NYHA Functional Class
8.
Quality of Life Survey (EQ-5D)
9.1.1 SUBJECT SCREENING
All subjects diagnosed with aortic stenosis requiring aortic valve replacement seen by 
cardiac surgeons participating in this clinical investigation should be screened for 
eligibility. All subjects who meet eligibility requirements will be asked to participate. A 
Screening Log will be provided to the investigational centers to maintain a cumulative 
log of all screened subjects admitted for aortic valve replacement by the cardiac 
surgeons participating in this investigation. For subjects listed as not eligible for 
participation in the clinical investigation, a reason supporting the disqualification of the 
subject must be entered on the screening log. The Screening Log shall be duly 
completed and faxed to the Investigation Sponsor regularly (at least once per month). 
Any subject deemed ineligible due to active endocarditis, recent myocardial infarction, 
pregnancy or lactating, or due to participation in another clinical investigation may be 
re-screened at a later time. Re-screened subjects must be re-entered on the Screening 
Log.  
9.1.2 INFORMED CONSENT
Subjects who are eligible for participation in the clinical investigation shall be provided 
at a minimum with the following explanation:   
1. background of the clinical investigation;
2. potential benefits and risks of the procedures involved;
3. follow-up visit requirements per the clinical investigation.
Each subject shall be given ample time to read the Informed Consent in its entirety and 
ask questions to make an informed decision. The subject must sign and date the 
investigational center’s Ethics Committee (EC) approved Informed Consent before any 
clinical investigation specific procedure is applied to the subject. Subjects who provide 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 28 of 54 
 
 
informed consent will be assigned a unique investigation subject identification number 
that will be recorded on the Screening Log. The Investigator, or designee, and any 
witnesses shall also sign and date the consent form, as indicated. Failure to provide 
Informed Consent renders the subject ineligible for participation in the clinical 
investigation including undergoing treatment with the investigational devices. Subjects 
who do not provide informed consent also are recorded on the Screening Log. 
For subjects who are not able to read or write and or are blind, a legal representative 
who is authorized to sign and date the consent on the subject’s behalf will do so, but 
only after the informed consent is read and explained, all questions answered and 
understood by the subject and legal representative and the subject has given verbal 
agreement to volunteer for the clinical investigation. An independent witness (other 
than the subject’s legal representative or the consenting physician) shall be present 
throughout the process. A note will be made of the subject’s verbal agreement to 
participate; furthermore the witness shall also sign and personally date the informed 
consent form attesting that the information was accurately explained and that 
informed consent was freely given.   
9.1.3 BASELINE ASSESSMENT 
After a written informed consent has been obtained from the subject the following 
baseline tests and exams will be conducted: transthoracic echocardiography (TTE) per 
protocol (Section 9.5); 12-lead electrocardiogram; blood studies per protocol; an 
assessment per NYHA Functional Classification; completion of a Quality of Life Survey 
(EQ-5D); a pregnancy test (not applicable if subject is male or female who is post-
menopausal / surgically sterile). Test results conducted within 30 days before aortic 
valve surgery may be used for this investigation if all values per protocol are available. 
Baseline information to be documented is further detailed in Table 1. 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 29 of 54 
 
 
Table 1:  Baseline Assessment 
General information 
Clinical information 
Blood studies 
Echocardiography9
Birth Date 
 
Subject Sex 
Height 
Weight 
Heart rate 
Cardiac Rhythm (12-
lead EKG) 
NYHA Classification 
Cardiovascular Risk 
Factors 
Cardiovascular 
Conditions 
Previous Procedures 
/ Interventions 
Non-Cardiovascular 
Conditions 
Quality of Life 
Blood Draw Date 
White Blood Cell 
Count 
Red Blood Cell Count 
Hemoglobin 
Hematocrit 
Haptoglobin 
Reticulocytes 
Platelet Count 
Serum Lactate 
Dehydrogenase 
Date of exam 
2D measurements 
Ejection fraction 
Aortic bioprosthesis 
assessment 
LVOT assessment 
Mitral Valve 
assessment 
Other Variables 
Left Ventricular 
Assessment 
9.2 
SURGICAL PROCEDURE 
9.2.1 PROCEDURE PREPARATION 
The surgical approach used will be at the discretion of the investigator in his/her 
routine surgical practice. At the time of aortic valve replacement a transesophageal 
echocardiogram to further assess the anatomy (See Intra-operative Exclusion criteria 
section 6.3) is recommended prior to aortic valve replacement with the EDWARDS 
INTUITY Aortic Valve. After performing the aortotomy, the native valve and 
surrounding anatomy should be examined for compatibility with the devices (See 
Intra-operative Exclusion criteria section 6.3). 
9.2.2 EDWARDS INTUITY AORTIC VALVE IMPLANTING PROCEDURE 
A detailed description of device preparation and use is provided in the Instructions for 
Use (IFU) of both Models 8300ACA and 8300ACB, (See Clinical Investigator’s Brochure). 
Investigators must be familiar with Precautions and Technique information described 
in the IFU prior to use of the bioprosthesis and the delivery system. The EDWARDS 
INTUITY Valve System implanting procedure uses one bioprosthesis and one delivery 
system. A second attempt, with new devices, is permitted.  If the second attempt is not 
successful, no further attempts are permitted and the subject should be treated with 
another surgical valve. 
A Transesophageal echo (TEE) should be performed after the bioprosthesis is 
implanted to assess placement, potential paravalvular leak, and mitral valve function. 
Procedural information, findings, results and device identification information to be 
recorded is identified in Table 2. 
29
9 Data evaluation to be performed by a Core Lab as described in the Echo Manual. 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 30 of 54 
 
 
Table 2: Procedural information 
General information 
Clinical information 
Device performance 
Date of Admission 
Date of Procedure 
Implanting Surgeon 
Type of Operation 
Etiology 
Diagnosis for replacement 
Valve implantation 
Condition of the native aortic valve 
Sizing 
Concomitant procedures 
Intraoperative Adverse Events 
Bioprosthesis size and serial 
number 
Delivery system size, lot, and 
components used 
Device technical success 
9.3 
SUBJECT ENROLLMENT 
Subjects will be considered enrolled into the clinical investigation after meeting all the 
enrollment criteria, signing the informed consent, and after the surgeon sizes the 
aortic annulus, and determines that the bioprosthesis can be implanted. The point of 
enrollment in Phase I and Phase II of the clinical investigation is established in the 
Operating Room when the investigator sizes the aortic annulus and confirms that the 
subject is an appropriate candidate for the investigation device(s)10
9.4
. All subjects 
enrolled in this clinical investigation must be followed as described in section 
 and 
section 9.5 
Adverse events are collected from the time the subject provides consent. 
9.4 
POST-PROCEDURE 
9.4.1 POST-PROCEDURE CARE 
Bioprosthetic heart valve recipients should be maintained on anticoagulant therapy 
(except when contraindicated) during the initial healing stages after implantation, 
approximately 2 to 3 months in accordance with the ACC/AHA 2006 Guidelines for the 
Management of Patients with Valvular Heart Disease [8]. Anticoagulants should then 
be discontinued over a period of 10 days, except in those subjects for whom ongoing 
anticoagulant protection is indicated, i.e., in the absence of sinus rhythm and in 
subjects with a dilated left atrium, calcification of the atrial wall, history of previous 
atrial thrombus, or any other medical condition requiring anticoagulation therapy. 
However, the appropriate anticoagulation therapy must be determined by the 
physician on individual basis. 
It is recommended to collect post-operative telemetry on all subjects for a minimum of 
five (days) after aortic valve replacement. 
9.4.2 DISCHARGE 
A clinical evaluation of Phase I or Phase II subjects, including an echocardiogram (refer 
to Section 9.5), will be performed at the time of hospital discharge. Medical 
information, findings, and results to be recorded are identified in Table 3. 
30
10 The bioprosthesis and the delivery system must be used. 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 31 of 54 
 
 
Table 3:  Discharge Evaluation 
General information Clinical information 
Echocardiography11
Date of Discharge 
 
Weight 
Heart rate 
Cardiac Rhythm (12-lead EKG) 
Anti-thromboembolic therapy 
Adverse Events  
Coagulation Profile 
Date of exam 
2D measurements 
Ejection fraction 
Aortic bioprosthesis assessment 
LVOT assessment 
Mitral Valve assessment 
Other Variables 
Left Ventricular Assessment 
Subjects, who are not discharged within 10 days post procedure must have an 
echocardiogram (refer to Section 9.5) to further assess placement and performance of 
the bioprosthesis. This echocardiogram is required to complete the evaluation of 
procedural success. Those subjects will not require an additional echocardiogram at 
discharge. 
9.4.3 FOLLOW-UP ASSESSMENTS 
Post-procedure clinical evaluation will be performed on all Phase I or Phase II of 
enrolled subjects at 1 month, 3 months, 1 year and annually thereafter until 5 years of 
follow-up is achieved.  The follow-up windows are listed in Table 4. 
Table 4:  Follow-up Windows 
Follow-up Assessment12
Assessment Window 
 
1-month
± 1 week 
3-months
+ 1 month
1-year
± 1 month 
2-year
± 1 month 
3-year
± 1 month 
4-year
± 1 month 
5-year
± 1 month 
During the Phase I 1-month evaluation of the subject a 12 lead electrocardiogram and 
a Transthoracic echocardiography (TTE) per protocol (Section 9.5) is required. Medical 
information and findings to be recorded are identified in Table 5.  
31
11 Data evaluation to be performed by a Core Lab as described in the Echo Manual. 
12 1 week = 7 days; 1 month = 30 days; 3 months = 90 days; 1 year = 365 days. 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 32 of 54 
 
 
Table 5:  Phase I Follow-up Evaluation at 1 Month 
General information 
Clinical information 
Echocardiography13
Date of Evaluation 
 
Cardiac Rhythm 
Weight 
Heart rate 
Adverse Events 
Date of exam 
2D measurements 
Ejection fraction 
Aortic bioprosthesis 
assessment 
LVOT assessment 
Mitral Valve assessment 
Other Variables 
Left Ventricular Assessment 
During the Phase II 1-month evaluation subject will be contacted to assess his/her 
current status. Medical information and findings to be recorded are identified in Table 
6. It is acceptable to obtain the information through an evaluation conducted via
telephone. Should the subject return, for any reason, to the investigational center for
the Phase II 1-month evaluation, assessments of the cardiac rhythm, weight, heart
rate, NYHA functional classification and a Transthoracic echocardiography (TTE) are
requested.
Table 6:  Phase II Follow-up Evaluation at 1 Month 
General information 
Clinical information 
Date of Evaluation 
Adverse Events 
During the subsequent 3 months, and annual visits, for Phase I or Phase II of the study, 
the subject returns to the investigational center for the evaluations listed in Table 7 
At each postoperative assessment, the investigator(s) will determine the subject's 
availability for future follow-up visits. If any subject is seen at a time other than a 
regularly scheduled follow-up visit (called an interim visit), the same information as 
described in Table 7 will be collected and documented by the investigator. 
32
13 Data evaluation to be performed by a Core Lab as described in the Echo Manual. 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 33 of 54 
 
 
Table 7: Follow-up evaluations 
General information Clinical information 
Blood studies 
Echocardiography14
Date of Evaluation 
 
Cardiac Rhythm 
Physical Assessment 
NYHA Classification 
Coagulation Profile 
Anti-thromboembolic 
therapy 
Adverse Events 
Quality of Life (at 3-
months and 1-year) 
Blood Draw Date 
White Blood Cell 
Count 
Red Blood Cell Count 
Hemoglobin 
Hematocrit 
Haptoglobin 
Reticulocytes 
Platelet Count 
Serum Lactate 
Dehydrogenase 
Date of exam 
2D measurements 
Ejection fraction 
Aortic bioprosthesis 
assessment 
LVOT assessment 
Mitral Valve 
assessment 
Other Variables 
Left Ventricular 
Assessment 
9.5 
ECHOCARDIOGRAM 
 All echocardiograms will be independently analyzed by the Echocardiography Core Lab 
as described in the Echo Manual 
. Each investigation 
echocardiogram is to be recorded individually on a computer disc (CD) with the 
individual subject investigation number provided on the examination screen. 
9.6 
DEVICE REMOVAL / EXPLANT PROCEDURE 
Subjects with device removal or explant will be followed as described in section 9.4 
and section 9.5; however neither echocardiography nor blood tests will be performed 
after discharge, unless required to better assess subject’s health status. 
9.6.1 INTRA-OPERATIVE REMOVAL 
Intra-operative removal is the excision of the investigation bioprosthesis before the 
EDWARDS INTUITY Valve System procedure was completed. The heart was not 
restarted with the bioprosthesis implanted. During the aortic valve replacement (AVR) 
procedure, should removal of the bioprosthesis be required after the frame was 
expanded, use of a nerve hook is recommended. Using a scalpel the operator shall 
carefully cut the bioprosthesis holder retaining sutures and remove the complete 
delivery system. Then, insert the nerve hook through the outflow aspect of the 
bioprosthesis. Operator is to engage the expanded frame with the nerve hook and 
gently pull the frame inward.  Then, operator is to disengage the collapsed portion of 
the frame and engage the expanded frame at another location, gently pulling the 
frame inwards. The expanded frame should be engaged and collapsed at least at 3 
radial locations. Once the frame is collapsed, the operator shall cut the nadir sutures 
and remove the bioprosthesis with forceps.  
9.6.2 INTRA-OPERATIVE OR EARLY POST-OPERATIVE EXPLANT 
Intra-operative explant is the excision of the investigation bioprosthesis, or part of the 
investigation bioprosthesis, after the EDWARDS INTUITY Valve System procedure was 
completed and the heart was restarted with the bioprosthesis implanted. The 
33
14 Data evaluation to be performed by a Core Lab as described in the Echo Manual. 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 34 of 54 
 
 
bioprosthesis is explanted by accessing the aortic valve site and excising the valve as 
described in section 9.6.1.  
This procedure is also recommended in the early AVR post-operative period, before 
substantial ingrowth tissue has occurred. 
9.6.3 LATE POST-OPERATIVE EXPLANT 
During the late AVR post-operative period, should explantation of the bioprosthesis be 
required the device and the surrounding anatomy should be assessed (echo/x-ray or 
visually) to determine the most appropriate course of action. 
The bioprosthesis is designed to allow: 
•
Collapsing of the frame using a nerve hook.
•
Removal of the pericardial leaflets only.
•
Separation from the frame by severing the connections between the
bioprosthesis wireform and the frame.
•
Implantation of a transcatheter valve (Per Instructions For Use in regions where
such devices are approved for this intended use)
9.7 
MISSED SUBJECT VISITS 
The Investigator(s) will make every attempt to follow the subjects and subjects will be 
encouraged by the Investigator(s) to report any address or telephone number changes 
to the investigational center. They will also be informed of the importance of returning 
for scheduled follow-up visits even if they are not having any problems. 
If a subject cannot be reached for a follow-up visit, the Investigator will document on 
the eCRF, the efforts undertaken to contact the subject or the subject’s primary health 
care provider. These efforts should include 3 attempts of telephone contacts at 
separate dates and times, and a registered letter before the end of the follow-up 
window. 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 on the date of last attempted 
contact. Subjects who miss a visit will not be considered withdrawn. At the next visit 
interval, the Investigator and/or designee will attempt to contact the subject again for 
follow-up. Should this attempt to contact the subject fail, a family member should be 
contacted in addition to the subject. Subjects who miss 2 sequential follow-up visits 
will be considered lost to follow-up at the second missed visit and exempt from future 
investigation follow-up visits. After the subject is terminated from the investigation, 
the Investigator will attempt to determine if the subject is alive, including searching 
national mortality registries as permitted by local laws. 
9.8 
INVESTIGATION SUBJECT EXIT 
Investigation Subjects exit the investigation when no additional follow-up visits, 
procedures, or data collection are required. A subject is exited from the investigation 
in the following instances: 
 
Subject fails enrollment criteria after written consent (section 6) 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 35 of 54 
 
 

Subject is excluded intra-operatively by investigator prior to attempted 
placement of the investigational device (section 6.3) 

Subject is Lost-to-follow-up (section 9.7) 

Subject withdraws from the investigation (section 6.3) 

Subject Death (section 11.3.1) 

Subject completes investigation follow-up (section 9.4.3
9.9 
CLINICAL INVESTIGATION TERMINATION 
The principal investigator(s) will be notified in writing upon termination of the clinical 
investigation. The Investigation Sponsor retains the right to suspend or terminate this 
clinical investigation at any time. Safety review committees associated with the clinical 
investigation may recommend termination should safety concerns warrant such 
action. Upon investigation termination, the Investigator will contact the investigation 
subjects to perform a final follow-up assessment within 2 months of investigation 
termination. If a subject completed a protocol scheduled clinical evaluation within 6 
months prior to investigation termination, the final follow-up assessment may be 
completed by telephone. Subjects should continue seeing their physicians as part of 
routine clinical follow-up after heart valve replacement surgery. 
10 DATA COLLECTION AND REPORTING 
10.1 DATA COLLECTION METHODS 
All required data for this investigation are to be collected with standardized Case 
Report Forms (CRFs) for individual subjects; samples are provided in Section 17.8. 
Electronic CRFs (eCRFs) will be utilized for this investigation. eCRFs must be 
electronically signed by the Principal Investigator or co-Investigator listed in the Clinical 
Studies Agreement and Delegation of Authority Log. If for any reason the eCRFs are 
unavailable and/or inaccessible, paper CRFs will be provided by the Investigation 
Sponsor to be completed, signed by the Principal Investigator or designee and 
submitted to the Investigation Sponsor. 
Primary data collection should be drawn from hospital chart and operator worksheet 
(source document) reviews. eCRFs must be kept current to reflect subject status during 
the course of the investigation.  
Case Report Form Instructions will be provided to assist the Investigator(s) and 
appropriate investigation staff in the completion of the required eCRFs. 
10.2 SOURCE DOCUMENTATION REQUIREMENTS 
Regulations require that Investigators maintain information in the clinical investigation 
subject’s medical records that corroborate data collected on the eCRFs. In order to 
comply with these regulatory requirements, the following information will be 
maintained as required by the Investigation Sponsor monitors and/or regulatory 
inspectors: 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 36 of 54 
 
 
1.
Medical history and physical condition of the clinical investigation subject
before involvement in the clinical investigation sufficient to verify protocol
entry criteria
2.
Dated and signed notes in the subject’s medical record on the day of entry
into the clinical investigation.
3.
Dated and signed notes, laboratory records, and test reports, from each
clinical investigation subject visit with reference to the eCRFs for further
information, if appropriate (for specific results of procedures and exams).
4.
Notations on abnormal lab results and adverse events reported and their
resolution.
5.
Notes regarding concomitant anticoagulant/antithrombotic medications
taken during the clinical investigation
6.
Subject’s condition upon completion of or withdrawal from the clinical
investigation.
10.3 QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES 
Because of the potential for errors or inaccuracies in entering data into eCRFs, originals 
or photocopies of all relevant procedural records and reports, post-procedural 
examinations, laboratory and other test results may be kept on file in the Investigator’s 
subject files. eCRFs and copies of test results must be available at all times for 
inspection by the investigation monitor. 
Data Management personnel will employ a full-featured relational Oracle database 
application on a central server. The application provides the capability of data 
collection remotely through the Internet so the participating site personnel may log on 
the system securely and enter the data. Other data management programming and/or 
data analyses will be done in the database system through the sponsor’s internal 
network. All subjects’ data collected in the system will be extensively verified through 
data validation programs, database integrity rules, and investigation-specific data 
entry conventions for data accuracy and logical meaningfulness. Periodic analysis of all 
subjects’ collected data will be performed in order to examine the expected 
distributions of data and to identify outliers for possible data entry errors. 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 37 of 54 
 
 
11 REPORTABLE EVENTS / EFFECTS 
Reportable event codes are provided in the eCRF synopsis for this investigation. 
11.1 REPORTING PROCEDURE 
Adverse event information will be reported throughout the clinical investigation as 
they occur. Adverse events will be followed until they are adequately resolved or 
explained. The investigator(s) will report any serious adverse event to the Investigation 
Sponsor’s Clinical Research department no later than three calendar days after the 
Investigators first learns of the event, followed by relevant source documents in ten 
working days. It is preferable for the investigator to notify the Investigation Sponsor’s 
Clinical Research department within 24 hours of occurrence or knowledge of the 
device 
related 
event. 
Notification 
should 
be 
done 
via 
email 
to 
HVTClinicalEU@edwards.com 
or 
faxed 
to 
+41-22-787-4324. 
In 
addition, 
investigational centers will report all serious adverse events to their local EC and 
National Competent Authority in accordance with the review committee’s and national 
requirements. 
11.2 DEFINITIONS 
For purposes of this protocol adverse event definitions are taken from the guidance 
ISO document; please refer to ISO 14155:2011. 
11.2.1 ADVERSE EVENT
An adverse event (AE) is defined as any untoward medical occurrence, unintended 
disease or injury, or untoward clinical signs (including abnormal laboratory findings) in 
subjects, users or other persons, whether or not related to the investigational medical 
device.  
NOTE 1: This definition includes events related to the investigational medical device or 
the comparator.  
NOTE 2: This definition includes events related to the procedures involved.  
NOTE 3: For users or other persons, this definition is restricted to events related to 
investigational medical devices. 
11.2.2 ADVERSE DEVICE EFFECT
An adverse device effect (ADE) is defined as any adverse event related to the use of an 
investigational medical device.  
NOTE 1: This definition includes adverse events resulting from insufficient or 
inadequate instructions for use, deployment, implantation, installation, or operation, or 
any malfunction of the investigational medical device. 
NOTE 2: This definition includes any event resulting from use error or from intentional 
misuse of the investigational medical device . 
11.2.3 SERIOUS ADVERSE EVENT  
A serious adverse event (SAE) is defined an adverse event that:  
a. led to death,
b. led to a serious deterioration in the health of the subject, that either resulted in:

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 38 of 54 
 
 
1. a life-threatening illness or injury, or
2. a permanent impairment of a body structure or a body function, or
3. in-patient or prolonged hospitalization, or
4. medical or surgical intervention to prevent life-threatening illness or
injury or permanent impairment to body structure or a body function,
c.
led to fetal distress, fetal death or a congenital abnormality or birth defect.
NOTE: Planned hospitalization for a pre-existing condition, or a procedure required by
the CIP, without serious deterioration in health, is not considered a serious adverse
event.
11.2.4 SERIOUS ADVERSE DEVICE EFFECT 
A serious adverse device effect (SADE) is defined as an adverse device effect that 
results in any of the consequences characteristics of a serious adverse event. 
11.2.5 UNANTICIPATED SERIOUS ADVERSE DEVICE EFFECT (USADE) 
Serious Adverse Device Effect which by its nature, incidence, severity or outcome, has 
not been identified in the current version of the risk analysis. 
Note:  Anticipated serious device effect (ASADE) is an effect which by its nature, 
incidence, severity or outcome has been identified in the risk analysis report. 
11.3 DEATHS AND EXPLANTS 
11.3.1 SUBJECT DEATHS 
In the event of subject death, every effort should be made to obtain a copy of the 
death certificate, the autopsy report and/or the death summary. Information on the 
cause of death and its relationship to the device used in this clinical investigation will 
be determined by the principal investigator. Copies of an autopsy report, if available, 
and/or a death summary are to be sent to the Investigation Sponsor. 
If a device is explanted during autopsy, the device should be returned to the 
Investigation Sponsor for analysis. Return kits for devices will be provided upon 
request by the clinical monitor.  
11.3.2 DEVICE EXPLANTS 
In the event a bioprosthesis is explanted in the intra-operative or early post-operative 
period (i.e., while the subject is hospitalized at the investigational center), a copy of 
the procedure report must be provided to the Investigation Sponsor.  Information on 
the cause of explant and its relationship to the bioprosthesis will be determined by the 
principal investigator. Explanted bioprostheses during this period must be returned to 
the Investigation Sponsor for analysis. Return kits for devices will be provided upon 
request by the clinical monitor. 
In the event a bioprosthesis is explanted in the late post-operative period, every effort 
should be made to obtain a copy of the explant procedure report, as applicable. 
Information on the cause of explant and its relationship to the bioprosthesis will be 
determined by the principal investigator. Copies of an explant report, if available, are 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 39 of 54 
 
 
to be sent to the Investigation Sponsor. Explanted bioprostheses during this period 
should be returned to the Investigation Sponsor for analysis. Return kits for devices 
will be provided upon request by the clinical monitor. 
12 STATISTICAL ANALYSIS 
12.1 SAMPLE SIZE PHASE I 
The Phase I investigation will enroll 10 subjects for feasibility.  No statistical 
justification is established. 
12.2 SAMPLE SIZE PHASE II 
Phase II will enroll up to 340 subjects. The sample size is determined based on ISO5840 
requirements. The rational for the increase is based on estimation of the number of 
additional subjects required in order to reach a minimum of eight subjects implanted 
with the smallest valve size tested (19 mm valves) and a minimum of fifteen subjects 
implanted with the larger 27mm valve size tested to met ISO5840 requirements.  
12.3 PHASE I ANALYSIS  
Phase I consists of the first 10 subjects enrolled to the investigation. 
The following primary safety endpoints will be summarized by counts and percentages 
based on 30-day follow-up: 
-
study valve-related mortality,
-
thromboembolic events,
-
study valve thrombosis,
-
major bleeding events,
-
study  valve paravalvular leakage, and
-
study valve endocarditis.
In addition, the following safety endpoints will also be summarized by counts and 
percentages based on 30-day follow-up:  
-
all-cause mortality,
-
study  valve structural valve deterioration,
-
hemolysis,
-
study valve-related reoperation,
-
study valve explantation, and
-
all adverse events.
12.4 PHASE II ANALYSIS 
12.4.1 ANALYSIS POPULATION 
The primary safety analysis will include all the enrolled subjects including those 
enrolled in Phase I. The performance analysis will include the subjects who survived at 
least 30 days post implant. 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 40 of 54 
 
 
12.4.2 SAFETY ANALYSIS 
For reporting purposes, the percent of subjects who experience an early adverse event 
within 30 days of implant for the events listed in the primary safety endpoints will be 
summarized. Linearized rates will be used to summarize adverse events for the late 
(>30 days) post-operative period for the events listed in the primary safety endpoints. 
The linearized rates will be reported as the number of events occurring after the early 
post-operative period per year of subject survival. 
Actuarial analysis according to Kaplan-Meier will be used to estimate probability of 
freedom from each adverse event listed in the primary safety endpoint.  
The percentages for the early events and linearized rates for the late events will also 
be calculated for the other complications. 
Blood data (red blood count, white blood count, hematocrit, hemoglobin, platelet 
count, serum lactate dehydrogenase, haptoglobin, and reticulocytes) will be collected 
preoperatively, at 6-months, 1-years, and 5-years post implant. Data will be reported 
as the percent of subjects with results within the normal ranges at each time interval.  
12.4.3 PERFORMANCE ANALYSIS 
The device technical success and procedure success will be summarized by counts and 
percentages. 
Subjects will be analyzed according to the NYHA classification preoperatively, at 3 
months and annually post implant for 5 years. The distribution (numbers of subjects 
and percentages) in the various NYHA classes will be tabulated at each follow-up 
interval.  
Echocardiography data will be obtained preoperatively, at discharge (or 10-days post 
implant, whichever occurs first), at 6-months and at 1, 3, and 5 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 size. 
Regurgitation data will be summarized using frequency at each severity level. 
Improvement in regurgitation at one year will be analyzed via the Wilcoxon Signed-
Rank test. Change at one year from baseline for all other hemodynamic outcomes will 
be analyzed using paired t-tests. 
12.4.4 MISSING DATA 
All statistical tests on the performance endpoints will be performed using only those 
subjects with available data required for endpoint analysis. No missing value 
imputation will be performed. 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 41 of 54 
 
 
13 MONITORING 
13.1 MONITORING METHODS 
The Investigation Sponsor will assign a monitor to monitor the progress of the clinical 
investigation at each investigational center. The monitor will remain in close contact 
with each investigational center throughout the duration of the investigation to 
provide any needed materials, (i.e. investigation forms) or answer any questions. The 
monitor will be responsible for verifying that the subject signed the consent, reviewing 
date recorded on the eCRFs, and visiting each investigational center periodically to 
observe investigation progress and compliance with clinical protocol and regulations 
applicable to this clinical investigation.  
Monitoring visits will be scheduled throughout the duration of the clinical investigation 
between the monitor and the principal investigator at a mutually convenient and 
available time. These visits will assure that the facilities are still acceptable, the 
protocol and investigational plan are being followed, the EC is notified of approved 
protocol changes as required, complete records are being maintained, appropriate 
timely reports have been made to the Investigation Sponsor the EC and the Competent 
Authority (as applicable), device and device inventory are controlled and the 
investigator is carrying out all agreed activities.  Any personnel changes must be 
reported to the monitor immediately and a training program scheduled and 
documented. Additionally, the monitor will do source data verification to assure CRF 
data accuracy and completeness.  The scope of monitoring is defined and will be 
conducted in accordance with the TRITON Study Monitoring Plan. 
To protect subject confidentiality, the subject’s name must not appear anywhere on 
the  imaging media sent prepared for evaluation by the core lab, or supporting 
documentation removed from the investigational center. Each page should be 
identified with the subject’s ID number only. All other subject identifiers (i.e., medical 
record number, personal number) are to be obscured.    
13.2 MONITORING PLAN 
Prior to subject enrollment, an initiation visit will be completed at each investigational 
center to ensure the following:   
1.
Ethics Committee and applicable regulatory body approvals have been
obtained and documented,
2.
The investigators and clinical investigation personnel are appropriately
trained and clearly understand the investigation,
3.
The investigators and clinical investigation personnel accept the obligations
incurred in undertaking this clinical investigation.
4.
The Delegation of Authority form has been completed properly
Periodic monitoring visits will be made at all enrolling investigational centers in 
accordance with center enrollment rates. Investigation centers should be visited a 
minimum of once each year by the monitor. 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 42 of 54 
 
 
Upon termination or conclusion of the clinical investigation, the monitor will perform a 
close-out visit.  
Monitoring activities are further described in the TRITON Study Monitoring plan for 
this investigation. 
13.3 PROTOCOL DEVIATION 
A protocol deviation is defined as an event where the Investigator or investigation 
personnel did not conduct the investigation according to the clinical protocol or the 
Clinical Investigation Agreement.  
Deviations shall be reported to the Investigation Sponsor regardless of whether 
medically justifiable or taken to protect the subject in an emergency. Subject specific 
deviations and non-subject specific deviations, (e.g. unauthorized use of an 
investigational device outside the investigation, unauthorized use of an investigational 
device by a physician who is not listed in the Clinical Investigation Agreement, etc.) will 
be reported in writing. Investigators will also adhere to procedures for reporting 
investigation deviations to their EC in accordance with their specific EC’s reporting 
policies and procedures. 
For reporting purposes, deviations are classified as major or minor: 
1.
Major deviations:
a. Any deviation from subject inclusion and exclusion criteria;
b. Any deviation from subject informed consent procedures;
c.
Unauthorized use of an investigational device outside the investigation;
d. Unauthorized use of an investigational device by a physician who is not
listed in the Clinical Investigation Agreement.
2.
Minor deviations:
a. Deviation from a protocol requirement such as incomplete/inadequate
testing procedures (unless procedure is optional or deemed medically
inadvisable to perform on subject);
b. Follow-up performed outside specified time windows.
13.3.1 
EXCEPTIONS 
Some information in this investigation is collected for Investigation Sponsor research 
purposes and is therefore not a reportable protocol deviation if absent.  
At Baseline this includes: 
 
Blood pressure 
 
Pre-operative risk scores 
(Additive euroSCORE, Logistic euroSCORE, STS risk score) 
 
Type of medication currently in use (ACE or ARB Inhibitors, ADP inhibitors, 
Antiarrhythmics, Anticoagulants, Antiplatelets, Beta Blocker, Glycoprotein 
IIb/IIIa inhibitor, Inotropes, Lipid Lowering, Nitrates, or Steroids) 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 43 of 54 
 
 
During the investigation procedure this includes: 

Surgical approach 

Suture technique 

Debridement procedure 

Surgical procedure timing 

Device procedure timing 

Inflation device used 

Balloon inflation pressure and number of inflations 

User assessment: device ease of use 
At hospital discharge this includes: 

Blood pressure 

Subject discharged to: home, another hospital, extended care 

Current medications 

Post-operative hospitalization 
(time in intensive care unit, intermediate care, general ward) 

Ventilation time 

Post-operative blood replacement, including Cell Saver amount auto transfused 
(in intensive care unit, intermediate care, general ward) 
At follow-up evaluation this includes: 

Visit type (Hospital/Clinic, In-patient admission, phone) 

Current medications 
13.4 COMMUNICATION PROCEDURES 
During the course of the clinical investigation, all correspondence (letters, telephone 
call, emails and faxes) regarding the investigation must be maintained in the 
investigation binder provided by the Investigation Sponsor. This binder must be made 
available for monitoring visits or audits. 
14 COMMITTEES 
14.1 DATA MONITORING COMMITTEE 
The Investigation Sponsor will appoint a Data Monitoring Committee (DMC) whose 
members will be independent of both the Investigation Sponsor and the Investigators. 
The role and composition of the DMC is described in the DMC Charter for this clinical 
investigation.  
14.2 CLINICAL EVENTS COMMITTEE 
The Investigation Sponsor will appoint a Clinical Events Committee (CEC) whose 
members will be independent of both the Investigation Sponsor and the Investigators. 
The role and composition of the CEC is described in the CEC Charter for this clinical 
investigation. 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 44 of 54 
 
 
15 ETHICAL AND REGULATORY CONSIDERATIONS 
15.1 APPLICABLE REGULATIONS AND GUIDELINES 
The clinical investigation will be conducted in compliance with the regulations set forth 
in Table 8. It is the responsibility of the investigator(s) and Sponsor to comply 
additionally with country specific regulations.  
Table 8:  Applicable Regulations and Guidelines 
Region 
Regulation / Guideline 
Europe 
- 2007/47/EC European Medical Device Directive (MDD)
- ISO 14155:2011 (Clinical investigation of medical devices for human
subjects – Good clinical practive)
- ISO 5840: 2005 (Cardiovascular implants-Cardiac valve prostheses)
- Declaration of Helsinki
- ISO 14971:2007 (Medical Devices – application of risk management to
medical devices)
Furthermore, the investigator will use as guidance pertinent sections of ICH E6 GCP or 
will comply with the laws of the applicable country, whichever will afford greater 
protection to subjects screened for participation in the clinical investigation and 
subjects who participate in the investigation. 
Principles protecting the rights, safety and well-being of human subjects, which are the 
most important considerations and shall prevail over interests of science and society, 
shall be understood, observed, and applied at every step in the clinical investigation. 
15.2 IMPROPER INFLUENCE 
The Sponsor shall avoid improper influence on, or inducement of, the subject, monitor, 
any investigator(s) or other parties participating in, or contributing to, the clinical 
investigation. The Investigators shall avoid improper influence on or inducement of the 
subject, sponsor, monitor, other investigator(s) or other parties participating in or 
contributing to the clinical investigation 
15.3 DATA PROTECTION AND SUBJECT CONFIDENTIALITY 
The Investigation Sponsor is dedicated to maintaining the confidentiality and privacy of 
subjects who volunteer to participate in the clinical investigation. Passwords are issued 
to appropriate personnel to insure confidentiality and protection of the database by 
allowing variable levels of access to the computer system. In addition, the principal 
investigator is responsible for maintaining confidentiality throughout the clinical 
investigation. The hard copies of the source documentation are to be maintained in a 
secure area with limited access. All subject identifiers will be obliterated from all 
photocopies of source documents that have been removed from the investigational 
center. Subject identifiers include, but are not limited to: subject’s name, social 
security number or equivalent, and medical / hospital number. All documents for the 
clinical investigation will identify the subject by a subject identification number 
assigned by the Investigation Sponsor. 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 45 of 54 
 
 
15.4 INFORMED CONSENT AND REVIEW COMMITTEES 
All subjects must provide written informed consent in accordance with the local 
investigational center’s EC rules and regulations. A copy of the consent form from each 
center must be forwarded to the Investigation Sponsor for review and approval prior 
to submitting it to the institutional review committee. Each center must provide the 
Investigation Sponsor with a copy of the investigational center’s EC approval letter 
(stating at a minimum, the clinical investigation name or identification number, 
protocol revision being approved and an approval date) and the informed consent 
prior to the initiation of enrollment at that center. If yearly approvals for the 
continuation of the investigation at each investigational center are required, they must 
also be forwarded to the Investigation Sponsor. 
If national or regional EC requirements are less strict than the requirements of ISO 
14155:2011, the Sponsor will apply the ISO14155:2011 requirements to the greatest 
extent possible, irrespective of any lesser requirements, and shall record such efforts. 
15.5 INVESTIGATOR RESPONSIBILITIES 
15.5.1 GENERAL DUTIES 
The investigator shall ensure that all work and services described herein, or incidental 
to those described herein, shall be conducted in accordance with the highest standards 
of medical and clinical research practice and the applicable regulations. The 
investigator shall be responsible for the day to day conduct of the clinical investigation 
and for the safety and well-being of human subjects enrolled. The investigator will 
provide copies of the current clinical protocol to all staff responsible for conduct of the 
clinical investigation. 
The principal investigator is responsible for obtaining EC approval to start the clinical 
investigation at his/her investigational center.  
If there is a change or addition of co-investigator, an amended Clinical Investigation 
Agreement must be completed promptly. 
15.5.2 INVESTIGATOR RECORDS 
The principal investigator will maintain the accurate, complete, and current records 
relating to participation in this clinical investigation. Records including eCRFs and 
supporting data including hardcopies of all blood and diagnostic exams, signed Clinical 
Investigation Agreement, protocols and protocol amendments, signed informed 
consents, use of devices, EC approval letters, EC submissions, correspondence, 
including required reports and other documents pertaining to the conduct of the 
clinical investigation must be kept on file by the investigator. If the investigator(s) 
wishes to assign the files to someone else or remove them to another location, he/she 
should consult with the Investigation Sponsor in writing as to this change. Files for the 
clinical investigation must be maintained in a known location until the Investigation 
Sponsor notifies the investigator in writing that he/she may discard them.  

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 46 of 54 
 
 
15.5.3 INVESTIGATOR REPORTS 
The principal investigator will prepare and submit the following accurate and complete 
reports to the Investigation Sponsor and EC in a timely manner: 
-
Unanticipated adverse device effects (UADE) occurring during the clinical
investigation will be reported as soon as possible, but no later than 10 working
days after the principal investigator first learns of the event.
-
Serious adverse device effects (SADE) occurring during the clinical investigation
will be reported as described in Section 11.1.
-
Deviation from the clinical protocol (investigational plan) to protect the
subject’s life or physical well-being in an emergency will be reported to the
Investigation Sponsor and the EC within 5 working days.
-
Use of devices without informed consent will be reported to the Investigation
Sponsor within 5 working days after the use occurs.
-
Investigator will inform Edwards of any new information about the
investigation that may affect the health, safety or welfare of the subjects or
which may influence their decision to continue participating in the
investigation. Investigator is also responsible to inform the affected subject in
writing. If relevant, all affected subjects will be asked to confirm their
continuing informed consent in writing.
-
A final written report is submitted to the Investigation Sponsor and the EC
within three months of completion or termination of the investigation.
-
Upon request by a reviewing EC or the pertinent regulatory agencies, the
principal investigator will provide current information about any aspect of the
investigation.
15.6 INVESTIGATION SPONSOR RESPONSIBILITIES 
15.6.1 GENERAL DUTIES 
As the sponsor of this clinical investigation, Edwards Lifesciences has the overall 
responsibility for the conduct of the clinical investigation, including assurance that the 
investigation meets the regulatory requirements of the pertinent regulatory agencies. 
In this clinical investigation, Edwards Lifesciences will have certain direct 
responsibilities and will delegate other responsibilities to an Echocardiography Core 
Laboratory.  
15.6.2 SELECTION OF INVESTIGATORS
Edwards Lifesciences will select qualified investigators and will ship investigational 
devices to participating investigational centers only. Edwards Lifesciences will obtain 
signed investigator agreements and provide the Investigators with the information and 
supplies necessary to conduct the clinical investigation. 
15.6.3 MONITORING THE CLINICAL INVESTIGATION
Edwards will ensure compliance with the signed investigator’s agreement, the protocol 
(investigational plan), the requirements of applicable regulations and guidelines (see 
section 15.1), and any conditions of clinical investigation approval by the EC and 
regulatory bodies per written monitoring procedures.  

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 47 of 54 
 
 
Edwards will conduct and immediate investigation of any unanticipated adverse device 
effects (UADE) and if an event is found to present an unreasonable risk to subjects 
participating in this clinical investigation. Edwards will inform the Investigator of any 
new information about the investigation that may affect the health, safety or welfare 
of the subjects or which may influence their decision to continue participating in the 
investigation. Investigator will be responsible to inform the affected subject in writing. 
If relevant, all affected subjects will be asked to confirm their continuing informed 
consent in writing. 
15.6.4 SPONSOR RECORDS
Edwards Clinical Research will maintain accurate, complete, and current records 
relating to this clinical investigation. Records include eCRFs, signed Investigator 
Agreement, financial disclosure, protocols and protocol amendments, signed informed 
consents, device use, EC approval letters, EC submissions, correspondence, including 
required reports, and other documents. Edwards will maintain documentation during 
the clinical investigation and for up to two years after the clinical investigation is 
terminated or completed, or the records are no longer required to support a 
regulatory submission. Storage of the records may be designated to a third party.  
15.6.5 SPONSOR REPORTS 
Edwards Clinical Research will prepare and submit the following accurate and 
complete reports to the EC and the pertinent regulatory agencies in a timely manner: 
-
Withdrawal of EC approval will be reported to all EC and the pertinent
regulatory agencies within 5 working days of receipt of withdrawal of approval.
-
Withdraw of the pertinent regulatory agencies approval will be reported to
investigational centers and EC within 5 working days after receiving the notice
of approval withdrawal.
-
Current investigator list will be submitted to the pertinent regulatory agencies
at 6-month intervals.
-
Progress reports to the EC at least annually and to the pertinent regulatory
agencies as required.
-
A final written report is to be completed and submitted to the EC and the
pertinent regulatory agencies within six months after completion or
termination of the investigation.
-
Use of the devices without informed consent will be reported to regulatory
authorities within 5 working days after notification of device use.
-
Upon request by a reviewing EC or the pertinent regulatory agencies, Edwards
will provide current information about any aspect of the investigation.
15.7 MODIFICATIONS 
Changes in the protocol may be made only by written amendment agreed upon by the 
sponsor, the regulatory agency, and if pertinent, the EC. As appropriate, the 
Investigation Sponsor will submit changes in the protocol to the pertinent regulatory 
agencies and investigators to obtain EC re-approval. 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 48 of 54 
 
 
15.8 CLINICAL INVESTIGATION COMPLETION OR TERMINATION AND CLOSE-OUT 
The principal investigator will be notified in writing upon termination/conclusion of the 
clinical investigation. The Investigation Sponsor retains the right to suspend or 
terminate this clinical investigation at any time. 
15.9 AUDITS AND INSPECTIONS 
In the event that audits are initiated by the sponsor or national/international 
regulatory authorities, the investigator shall allow access to the original medical 
records and provide all requested information. 
15.10 PUBLICATION POLICY 
At various milestones in the TRITON investigation, including the conclusion, it is 
intended that multi-center papers will be published, in peer-reviewed scientific 
journals and scientific meetings. These publications/presentations will be co-ordinated 
by Edwards via the Principal Investigator.  
Publication or presentations of the investigators site-specific study results of devices 
which have not been market released will require the review of Edwards regarding 
proprietary information which shall not be divulged. If requested by Edwards, 
investigator will delay submission of such manuscripts for publication to permit 
preparation and filing of related patent applications. Publication (abstracts and 
manuscripts) or presentation of the study results of market approved devices are 
subject to review by Edwards prior to submission or presentation. Edwards will 
review the manuscript within sixty (60) days after receipt. If a multi-center 
publication is not issued after 1 year from the conclusion of the TRITON investigation 
(final database closure), single-center results may be published with review by 
Edwards within 30 days of submission. Exceptions to this rule require prior approval 
from Edwards. 

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 49 of 54
 
 
16 REFERENCES 
1.
Al-Attar, N., Himbert, D., Descoutures, F., Iung, B., Raffoul, R., Messika-Zeitoun, D.,
Brochet, E., Francis, F., Ibrahim, H., Vahanian, A., and Nataf, P., Transcatheter aortic
valve implantation: selection strategy is crucial for outcome. Ann Thorac Surg
2009;87(6):1757-1762; discussion 1762-1753.
2.
Bakhtiary, F., Dzemali, O., Steinseiffer, U., Schmitz, C., Glasmacher, B., Moritz, A., and
Kleine, P., Hydrodynamic comparison of biological prostheses during progressive valve
calcification in a simulated exercise situation. An in vitro investigation. Eur J
Cardiothorac Surg 2008;34(5):960-963.
3.
Bakhtiary, F., Dzemali, O., Steinseiffer, U., Schmitz, C., Glasmacher, B., Moritz, A., and
Kleine, P., Opening and closing kinematics of fresh and calcified aortic valve
prostheses: an in vitro investigation. J Thorac Cardiovasc Surg 2007;134(3):657-662.
4.
Bessell, J. R., Gower, G., Craddock, D. R., Stubberfield, J., and Maddern, G. J., Thirty
years experience with heart valve surgery: isolated aortic valve replacement. Aust N Z J
Surg 1996;66(12):799-805.
5.
Bleiziffer, S., Ruge, H., Mazzitelli, D., Schreiber, C., Hutter, A., Krane, M.,
Bauernschmitt, R., and Lange, R., Valve implantation on the beating heart: catheter-
assisted surgery for aortic stenosis. Dtsch Arztebl Int 2009;106(14):235-241.
6.
Bleiziffer, S., Ruge, H., Mazzitelli, D., Schreiber, C., Hutter, A., Laborde, J. C.,
Bauernschmitt, R., and Lange, R., Results of percutaneous and transapical
transcatheter aortic valve implantation performed by a surgical team. Eur J
Cardiothorac Surg 2009;35(4):615-620; discussion 620-611.
7.
Bloomstein, L. Z., Gielchinsky, I., Bernstein, A. D., Parsonnet, V., Saunders, C., Karanam,
R., and Graves, B., Aortic valve replacement in geriatric patients: determinants of in-
hospital mortality. Ann Thorac Surg 2001;71(2):597-600.
8.
Bonow, R. O., Carabello, B. A., Kanu, C., de Leon, A. C., Jr., Faxon, D. P., Freed, M. D.,
Gaasch, W. H., Lytle, B. W., Nishimura, R. A., O'Gara, P. T., O'Rourke, R. A., Otto, C. M.,
Shah, P. M., Shanewise, J. S., Smith, S. C., Jr., Jacobs, A. K., Adams, C. D., Anderson, J.
L., Antman, E. M., Fuster, V., Halperin, J. L., Hiratzka, L. F., Hunt, S. A., Nishimura, R.,
Page, R. L., and Riegel, B., ACC/AHA 2006 guidelines for the management of patients
with valvular heart disease: a report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines (writing committee to revise the
1998 Guidelines for the Management of Patients With Valvular Heart Disease):
developed in collaboration with the Society of Cardiovascular Anesthesiologists:
endorsed by the Society for Cardiovascular Angiography and Interventions and the
Society of Thoracic Surgeons. Circulation 2006;114(5):e84-231.
9.
Bonow, R. O., Carabello, B., de Leon, A. C., Jr., Edmunds, L. H., Jr., Fedderly, B. J., Freed,
M. D., Gaasch, W. H., McKay, C. R., Nishimura, R. A., O'Gara, P. T., O'Rourke, R. A.,
Rahimtoola, S. H., Ritchie, J. L., Cheitlin, M. D., Eagle, K. A., Gardner, T. J., Garson, A.,
Jr., Gibbons, R. J., Russell, R. O., Ryan, T. J., and Smith, S. C., Jr., Guidelines for the
management of patients with valvular heart disease: executive summary. A report of
the American College of Cardiology/American Heart Association Task Force on Practice
Guidelines (Committee on Management of Patients with Valvular Heart Disease).
Circulation 1998;98(18):1949-1984.

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 50 of 54 
 
 
10.
Borger, M. A., Nette, A. F., Maganti, M., and Feindel, C. M., Carpentier-Edwards
Perimount Magna valve versus Medtronic Hancock II: a matched hemodynamic
comparison. Ann Thorac Surg 2007;83(6):2054-2058.
11.
Botzenhardt, F., Eichinger, W. B., Bleiziffer, S., Guenzinger, R., Wagner, I. M.,
Bauernschmitt, R., and Lange, R., Hemodynamic comparison of bioprostheses for
complete supra-annular position in patients with small aortic annulus. J Am Coll
Cardiol 2005;45(12):2054-2060.
12.
Botzenhardt, F., Eichinger, W. B., Guenzinger, R., Bleiziffer, S., Wagner, I.,
Bauernschmitt, R., and Lange, R., Hemodynamic performance and incidence of patient-
prosthesis mismatch of the complete supraannular perimount magna bioprosthesis in
the aortic position. Thorac Cardiovasc Surg 2005;53(4):226-230.
13.
Braunwald, E., Heart Disease. 5 ed. 1997, Philadelphia: W.B. Saunders Company.
14.
Brogan, W. C., 3rd, Grayburn, P. A., Lange, R. A., and Hillis, L. D., Prognosis after valve
replacement in patients with severe aortic stenosis and a low transvalvular pressure
gradient. J Am Coll Cardiol 1993;21(7):1657-1660.
15.
Burr, L. H., Jamieson, W. R., Munro, A. I., Miyagishima, R. T., and Germann, E., Porcine
bioprostheses in the elderly: clinical performance by age groups and valve positions.
Ann Thorac Surg 1995;60(2 Suppl):S264-269.
16.
Carabello, B. A., Clinical practice. Aortic stenosis. N Engl J Med 2002;346(9):677-682.
17.
Cheitlin, M.D., Sokolow, M., and McIlroy, M.B., Clinical Cardiology. 1993, London:
Prentice-Hall International Inc.
18.
Chikwe, J., Walther, A., and Pepper, J., The Surgical Management of Aortic Valve
Disease. British Journal of Cardiology. 2003;10(6):453-461.
19.
Clavel, M. A., Webb, J. G., Pibarot, P., Altwegg, L., Dumont, E., Thompson, C., De
Larochelliere, R., Doyle, D., Masson, J. B., Bergeron, S., Bertrand, O. F., and Rodes-
Cabau, J., Comparison of the hemodynamic performance of percutaneous and surgical
bioprostheses for the treatment of severe aortic stenosis. J Am Coll Cardiol
2009;53(20):1883-1891.
20.
Connolly, H. M., Oh, J. K., Schaff, H. V., Roger, V. L., Osborn, S. L., Hodge, D. O., and
Tajik, A. J., Severe aortic stenosis with low transvalvular gradient and severe left
ventricular dysfunction:result of aortic valve replacement in 52 patients. Circulation
2000;101(16):1940-1946.
21.
Covello, R. D., Maj, G., Landoni, G., Maisano, F., Michev, I., Guarracino, F., Alfieri, O.,
Colombo, A., and Zangrillo, A., Anesthetic management of percutaneous aortic valve
implantation: focus on challenges encountered and proposed solutions. J Cardiothorac
Vasc Anesth 2009;23(3):280-285.
22.
Dalmau, M. J., Maria Gonzalez-Santos, J., Lopez-Rodriguez, J., Bueno, M., and Arribas,
A., The Carpentier-Edwards Perimount Magna aortic xenograft: a new design with an
improved hemodynamic performance. Interact Cardiovasc Thorac Surg 2006;5(3):263-
267.
23.
Dalmau, M. J., Maria Gonzalez-Santos, J., Lopez-Rodriguez, J., Bueno, M., Arribas, A.,
and Nieto, F., One year hemodynamic performance of the Perimount Magna
pericardial xenograft and the Medtronic Mosaic bioprosthesis in the aortic position: a
prospective randomized investigation. Interact Cardiovasc Thorac Surg 2007;6(3):345-
349.

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 51 of 54 
 
 
24.
David, I. B., Catinella, F., and Herskowitz, K., Does valve design impact the maximum
implantable bioprosthetic diameter? A prospective, multicenter observational
investigation. J Heart Valve Dis 2007;16(6):662-666; discussion 666.
25.
deFilippi, C. R., Willett, D. L., Brickner, M. E., Appleton, C. P., Yancy, C. W., Eichhorn, E.
J., and Grayburn, P. A., Usefulness of dobutamine echocardiography in distinguishing
severe from nonsevere valvular aortic stenosis in patients with depressed left
ventricular function and low transvalvular gradients. Am J Cardiol 1995;75(2):191-194.
26.
Del Valle-Fernandez, R. and Ruiz, C. E., Transcatheter heart valves for the treatment of
aortic stenosis: state-of-the-art. Minerva Cardioangiol 2008;56(5):543-556.
27.
Dzemali, O., Bakhtiary, F., Steinseiffer, U., Schmitz, C., Glasmacher, B., Moritz, A., and
Kleine, P., Hemodynamic performance of fresh and calcified aortic valve prostheses in
critical low stroke volume. J Heart Valve Dis 2008;17(3):317-324.
28.
Dzemali, O., Bakhtiary, F., Steinseiffer, U., Schmitz, C., Glasmacher, B., Moritz, A., and
Kleine, P., Impact of valve calcification on systolic and diastolic valvular function--an in
vitro model. J Cardiovasc Surg (Torino) 2008;49(6):817-824.
29.
European Commission, Council Directive 93/42/EEC of 14 June 1993 concerning
medical devices as amended by 7 December 2001 (MDD). 1993.
30.
Franco, K.L. and Verrier, E.D., Advanced Therapy in Cardiac Surgery. 2nd Edition ed.
2003, Hamilton, London: BC Decker Inc.
31.
Frank, S., Johnson, A., and Ross, J., Jr., Natural history of valvular aortic stenosis. Br
Heart J 1973;35(1):41-46.
32.
Fusari, M., Alamanni, F., Bona, V., Muratori, M., Salvi, L., Parolari, A., and Biglioli, P.,
Transcatheter aortic valve implantation in the operating room: early experience. J
Cardiovasc Med (Hagerstown) 2009;10(5):383-393.
33.
Gerosa, G., Tarzia, V., Rizzoli, G., and Bottio, T., Small aortic annulus: the hydrodynamic
performances of 5 commercially available tissue valves. J Thorac Cardiovasc Surg
2006;131(5):1058-1064.
34.
Iung, B., Baron, G., Butchart, E. G., Delahaye, F., Gohlke-Barwolf, C., Levang, O. W.,
Tornos, P., Vanoverschelde, J. L., Vermeer, F., Boersma, E., Ravaud, P., and Vahanian,
A., A prospective survey of patients with valvular heart disease in Europe: The Euro
Heart Survey on Valvular Heart Disease. Eur Heart J 2003;24(13):1231-1243.
35.
Karabulut, H., Toraman, F., Alhan, C., Camur, G., Evrenkaya, S., Dagdelen, S., and
Tarcan, S., EuroSCORE overestimates the cardiac operative risk. Cardiovasc Surg
2003;11(4):295-298.
36.
Kolh, P., Kerzmann, A., Lahaye, L., Gerard, P., and Limet, R., Cardiac surgery in
octogenarians; peri-operative outcome and long-term results. Eur Heart J
2001;22(14):1235-1243.
37.
Korfer, R., Schutt, U., Minami, K., Hartmann, D., Kortke, H., and Luth, J. U., Left
ventricular function in heart valve surgery: a multidisciplinary challenge. J Heart Valve
Dis 1995;4 Suppl 2:S194-197.
38.
MEDDEV 2.7.1., Evaluation of Clinical Data, a Guide for Manufacturers and Notified
Bodies. 2003.
39.
MEDDEV 2.12/2, Guidelines on post market clinical follow-up. 2004.

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 52 of 54 
 
 
40.
Mortasawi, A., Gehle, S., Schroder, T., Ennker, I. C., Rosendahl, U., Dalladaku, F., Bauer,
S., Albert, A., and Ennker, J., [Aortic valve replacement in 80- and over 80-year-old
patients. Short-term and long-term results]. Z Gerontol Geriatr 2000;33(6):438-446.
41.
Mullany, C. J., Aortic valve surgery in the elderly. Cardiol Rev 2000;8(6):333-339.
42.
Murakami, T., Kikugawa, D., Endou, K., Fukuhiro, Y., Ishida, A., Morita, I., Masaki, H.,
Inada, H., and Fujiwara, T., Changes in patterns of left ventricular hypertrophy after
aortic valve replacement for aortic stenosis and regurgitation with St. Jude Medical
cardiac valves. Artif Organs 2000;24(12):953-958.
43.
Nashef, S. A., Roques, F., Michel, P., Gauducheau, E., Lemeshow, S., and Salamon, R.,
European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac
Surg 1999;16(1):9-13.
44.
Nguyen, T.N., Practical Handbook of Advanced Interventional Cardiology. 2nd ed.
2003, New York: Blackwell Publishing, Inc.
45.
Noble, S. and Bonan, R., [Transcatheter aortic valve replacement]. Rev Med Suisse
2009;5(193):526-530.
46.
Nowicki, E. R., Birkmeyer, N. J., Weintraub, R. W., Leavitt, B. J., Sanders, J. H., Dacey, L.
J., Clough, R. A., Quinn, R. D., Charlesworth, D. C., Sisto, D. A., Uhlig, P. N., Olmstead, E.
M., and O'Connor, G. T., Multivariable prediction of in-hospital mortality associated
with aortic and mitral valve surgery in Northern New England. Ann Thorac Surg
2004;77(6):1966-1977.
47.
O'Brien, K. D., Zhao, X. Q., Shavelle, D. M., Caulfield, M. T., Letterer, R. A., Kapadia, S.
R., Probstfield, J. L., and Otto, C. M., Hemodynamic effects of the angiotensin-
converting enzyme inhibitor, ramipril, in patients with mild to moderate aortic stenosis
and preserved left ventricular function. J Investig Med 2004;52(3):185-191.
48.
Pereira, J. J., Lauer, M. S., Bashir, M., Afridi, I., Blackstone, E. H., Stewart, W. J.,
McCarthy, P. M., Thomas, J. D., and Asher, C. R., Survival after aortic valve replacement
for severe aortic stenosis with low transvalvular gradients and severe left ventricular
dysfunction. J Am Coll Cardiol 2002;39(8):1356-1363.
49.
Powell, D. E., Tunick, P. A., Rosenzweig, B. P., Freedberg, R. S., Katz, E. S., Applebaum,
R. M., Perez, J. L., and Kronzon, I., Aortic valve replacement in patients with aortic
stenosis and severe left ventricular dysfunction. Arch Intern Med 2000;160(9):1337-
1341.
50.
Rajamannan, N. M., Calcific aortic stenosis: medical and surgical management in the
elderly. Curr Treat Options Cardiovasc Med 2005;7(6):437-442.
51.
Rapaport, E., Natural history of aortic and mitral valve disease. Am J Cardiol
1975;35(2):221-227.
52.
Roques, F., Michel, P., Goldstone, A. R., and Nashef, S. A., The logistic EuroSCORE. Eur
Heart J 2003;24(9):881-882.
53.
Roques, F., Nashef, S. A., Michel, P., Gauducheau, E., de Vincentiis, C., Baudet, E.,
Cortina, J., David, M., Faichney, A., Gabrielle, F., Gams, E., Harjula, A., Jones, M. T.,
Pintor, P. P., Salamon, R., and Thulin, L., Risk factors and outcome in European cardiac
surgery: analysis of the EuroSCORE multinational database of 19030 patients. Eur J
Cardiothorac Surg 1999;15(6):816-822; discussion 822-813.

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 53 of 54 
 
 
54.
Schwarz, F., Baumann, P., Manthey, J., Hoffmann, M., Schuler, G., Mehmel, H. C.,
Schmitz, W., and Kubler, W., The effect of aortic valve replacement on survival.
Circulation 1982;66(5):1105-1110.
55.
Spargias, K., Manginas, A., Pavlides, G., Khoury, M., Stavridis, G., Rellia, P., Smirli, A.,
Thanopoulos, A., Balanika, M., Polymeros, S., Thomopoulou, S., Athanassopoulos, G.,
Karatasakis, G., Mastorakou, R., Lacoumenta, S., Michalis, A., Alivizatos, P., and
Cokkinos, D., Transcatheter aortic valve implantation: first Greek experience. Hellenic J
Cardiol 2008;49(6):397-407.
56.
Investigation Group 5, Clinical Evaluation, SG5/N2R8:2007, G.H.T. Force, Editor. 2007.
57.
Sundt, T. M., Bailey, M. S., Moon, M. R., Mendeloff, E. N., Huddleston, C. B., Pasque,
M. K., Barner, H. B., and Gay, W. A., Jr., Quality of life after aortic valve replacement at
the age of >80 years. Circulation 2000;102(19 Suppl 3):III70-74.
58.
Svensson, L. G., Dewey, T., Kapadia, S., Roselli, E. E., Stewart, A., Williams, M.,
Anderson, W. N., Brown, D., Leon, M., Lytle, B., Moses, J., Mack, M., Tuzcu, M., and
Smith, C., United States feasibility investigation of transcatheter insertion of a stented
aortic valve by the left ventricular apex. Ann Thorac Surg 2008;86(1):46-54; discussion
54-45.
59.
Talano, J.V. and Melek, B.H., Aortic Stenosis. eMedicine Journal 2006.
60.
Totaro, P., Degno, N., Zaidi, A., Youhana, A., and Argano, V., Carpentier-Edwards
PERIMOUNT Magna bioprosthesis: a stented valve with stentless performance? J
Thorac Cardiovasc Surg 2005;130(6):1668-1674.
61.
Vejlsted, H., Skagen, K., Hansen, P. F., and Halkier, E., Immediate and long-term results
in aortic valve replacement. Scand J Thorac Cardiovasc Surg 1984;18(1):41-44.
62.
Wagner, I. M., Eichinger, W. B., Bleiziffer, S., Botzenhardt, F., Gebauer, I., Guenzinger,
R., Bauernschmitt, R., and Lange, R., Influence of completely supra-annular placement
of bioprostheses on exercise hemodynamics in patients with a small aortic annulus. J
Thorac Cardiovasc Surg 2007;133(5):1234-1241.
63.
Walther, T., Chu, M. W., and Mohr, F. W., Transcatheter aortic valve implantation:
time to expand? Curr Opin Cardiol 2008;23(2):111-116.
64.
Walther, T., Falk, V., Dewey, T., Kempfert, J., Emrich, F., Pfannmuller, B., Broske, P.,
Borger, M. A., Schuler, G., Mack, M., and Mohr, F. W., Valve-in-a-valve concept for
transcatheter minimally invasive repeat xenograft implantation. J Am Coll Cardiol
2007;50(1):56-60.
65.
Walther, T., Falk, V., Kempfert, J., Borger, M. A., Fassl, J., Chu, M. W., Schuler, G., and
Mohr, F. W., Transapical minimally invasive aortic valve implantation; the initial 50
patients. Eur J Cardiothorac Surg 2008;33(6):983-988.
66.
Webb, J. G., Chandavimol, M., Thompson, C. R., Ricci, D. R., Carere, R. G., Munt, B. I.,
Buller, C. E., Pasupati, S., and Lichtenstein, S., Percutaneous aortic valve implantation
retrograde from the femoral artery. Circulation 2006;113(6):842-850.
67.
Webb, J. G., Pasupati, S., Humphries, K., Thompson, C., Altwegg, L., Moss, R., Sinhal, A.,
Carere, R. G., Munt, B., Ricci, D., Ye, J., Cheung, A., and Lichtenstein, S. V.,
Percutaneous transarterial aortic valve replacement in selected high-risk patients with
aortic stenosis. Circulation 2007;116(7):755-763.

TRITON Surgical Treatment of Aortic Stenosis with a Next Generation Surgical Aortic Valve  
Clinical Protocol Number: 2009-01
Revision E: September 15, 2011 
CONFIDENTIAL 
Page 54 of 54 
 
 
68.
Ye, J., Cheung, A., Lichtenstein, S. V., Altwegg, L. A., Wong, D. R., Carere, R. G.,
Thompson, C. R., Moss, R. R., Munt, B., Pasupati, S., Boone, R. H., Masson, J. B., Al Ali,
A., and Webb, J. G., Transapical transcatheter aortic valve implantation: 1-year
outcome in 26 patients. J Thorac Cardiovasc Surg 2009;137(1):167-173.
69.
Ye, J., Cheung, A., Lichtenstein, S. V., Carere, R. G., Thompson, C. R., Pasupati, S., and
Webb, J. G., Transapical aortic valve implantation in humans. J Thorac Cardiovasc Surg
2006;131(5):1194-1196.
70.
Ye, J., Cheung, A., Lichtenstein, S. V., Pasupati, S., Carere, R. G., Thompson, C. R.,
Sinhal, A., and Webb, J. G., Six-month outcome of transapical transcatheter aortic
valve implantation in the initial seven patients. Eur J Cardiothorac Surg 2007;31(1):16-
21.
71.
Zajarias, A. and Cribier, A. G., Outcomes and safety of percutaneous aortic valve
replacement. J Am Coll Cardiol 2009;53(20):1829-1836.
72.
Zierer, A., Wimmer-Greinecker, G., Martens, S., Moritz, A., and Doss, M., The
transapical approach for aortic valve implantation. J Thorac Cardiovasc Surg
2008;136(4):948-953.
73.
Chitwood, WR Minimally Invasive Valve Surgery: Trends for the Future. Euro J Card-
Thorac Surg 1999; 16 (Suppl 1): S64-S65.
74.
Plass A, Scheffel H, Alkadhi H, Kaufmann P, Genoni M, Falk V, Grünenfelder J. Aortic
valve replacement through a minimally invasive approach: preoperative planning,
surgical technique, and outcome. Ann Thorac Surg. 2009 Dec; 88(6): 1851-6.