C-Pulse Implantable Counterpulsation Pump (ICP) Feasibility Study - A Heart Assist System
Phase: NA
Conditions: Heart Failure
Sponsor: Nuwellis, Inc.

 
 
 
 
 
 
 
 
 
 
 
 
 
 
C–Pulse® Implantable 
Counterpulsation Pump (ICP) 
A Heart Assist Device 
 
March 4, 2015 
 
Investigational Plan 
 
 
 
 
 
 
 
Confidential 
© Sunshine Heart 
PRO 02291–I 
NCT00815880

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TABLE OF CONTENTS 
TRIAL CONTACT INFORMATION ........................................................................................................................ 7 
INTRODUCTION ........................................................................................................................................................ 8 
Purpose ........................................................................................................................................................ 8 
Study Size and Duration............................................................................................................................. 8 
Background ................................................................................................................................................. 9 
C-P ULSE DEVICE DESCRIPTION ........................................................................................................................ 13 
The Sunshine Heart C–Pulse® ICP System ............................................................................................ 13 
System Features ........................................................................................................................................ 15 
Indications for Use and Intended Use ..................................................................................................... 15 
Summary of Implant procedure .............................................................................................................. 15 
STUDY DESCRIPTION ............................................................................................................................................ 17 
Design ......................................................................................................................................................... 17 
Objectives .................................................................................................................................................. 18 
Primary Objectives ................................................................................................................................. 18 
Secondary Objectives ............................................................................................................................. 18 
Patient Selection ........................................................................................................................................ 20 
Inclusion Criteria .................................................................................................................................... 20 
Exclusion Criteria................................................................................................................................... 20 
Investigational Center Information ......................................................................................................... 22 
Number of Sites ..................................................................................................................................... 22 
Investigator Agreement/Financial Disclosure ........................................................................................ 22 
Investigational Review Board ................................................................................................................ 22 
Access to Center and Study Materials .................................................................................................... 22 
Confidentiality ....................................................................................................................................... 23 
Attending Investigator Meetings or Conference Calls ........................................................................... 23 
Required Equipment ............................................................................................................................... 23 
Supply of Study Materials and Device Accountability .......................................................................... 23 
Criteria for Early Termination or Suspension ........................................................................................ 23 
Laboratory Accreditation and Normal Values ....................................................................................... 24 
Procedures ................................................................................................................................................. 24 
Screening and Patient Informed Consent ............................................................................................... 24 
Patient Withdrawal or Loss to Follow–Up ............................................................................................. 25 
Data Collection Overview ...................................................................................................................... 25 
Summary of Required Testing ............................................................................................................... 29 
Clinical Procedures – Implant through discharge .................................................................................. 35 
Readmission ........................................................................................................................................... 40 
Post-Implant Follow–up Testing and Data Collection ........................................................................... 41 
Adverse Event Reporting ....................................................................................................................... 41 
Patient Deaths......................................................................................................................................... 47 
Explant Handling and Final Device Disposition .................................................................................... 48 
Patient Withdrawal and Study Exit ........................................................................................................ 48 

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STATISTICAL METHODS AND DATA ANALYSIS ............................................................................................ 49 
Justification of Methodology ..................................................................................................................49 
Primary Safety Measures ........................................................................................................................49 
Efficacy measurements ...........................................................................................................................50 
Secondary Objectives ..............................................................................................................................51 
RISK ANALYSIS ........................................................................................................................................................ 53 
Potential Risks ........................................................................................................................................53 
Risk Minimization ..................................................................................................................................59 
C-Pulse® Potential Benefits ....................................................................................................................60 
Justification for the Investigation ............................................................................................................61 
STUDY OVERSIGHT AND INTEGRITY ............................................................................................................... 65 
Designation of Sponsor, Data Manager, and Auditor ............................................................................65 
MONITORING PROCEDURES ............................................................................................................................... 66 
Summary of Monitoring Procedures and Responsibilities ....................................................................66 
Interim Monitoring Visits .........................................................................................................................66 
Study Closure .............................................................................................................................................67 
Name and Address of Study Monitors .....................................................................................................67 
Study Safety ...............................................................................................................................................67 
TRAINING PROCEDURES ...................................................................................................................................... 69 
PROTOCOL DEVIATIONS ...................................................................................................................................... 70 
RECORDS AND REPORTS ...................................................................................................................................... 72 
Investigational Records .............................................................................................................................72 
Investigator Reports ..................................................................................................................................72 
Sponsor Records ........................................................................................................................................74 
Sponsor Reports.........................................................................................................................................74 
PUBLICATION STRATEGY .................................................................................................................................... 75 
Publication Committee ..............................................................................................................................75 
Authorship Selection .................................................................................................................................75 
Review and Communication Guidelines ..................................................................................................76 
Ancillary Publications ...............................................................................................................................76 
APPENDIX A:  ABBREVIATIONS AND ACRONYMS ........................................................................................ 77 
APPENDIX B:  NATIONAL CO–PRINCIPAL INVESTIGATORS ..................................................................... 78 
APPENDIX C:  PARTICIPATING INSTITUTIONS ............................................................................................. 79 
APPENDIX D:  IRB LIST .......................................................................................................................................... 80 
APPENDIX E:  SUMMARY OF PREVIOUS STUDIES ........................................................................................ 81 
Intra–operative clinical feasibility study .................................................................................................81 
Long–term extra–aortic balloon counterpulsation in sheep ..................................................................81 
Prospective Observational Study .............................................................................................................82 
APPENDIX F:  LABELING AND OPERATOR MANUAL ................................................................................... 84 
APPENDIX G:  SAMPLE HIPAA DISCLOSURE .................................................................................................. 85 
APPENDIX H:  SAMPLE INFORMED CONSENT ............................................................................................... 87 

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APPENDIX I:  REQUIRED TESTS ..................................................................................................................... 1102 
APPENDIX J:  CORE LABORATORIES ........................................................................................................... 4105 
Cardiopulmonary Exercise Testing .................................................................................................... 4105 
Echocardiography .............................................................................................................................. 4105 
CT Scan .............................................................................................................................................. 4105 
APPENDIX K:  SAMPLE CASE REPORT FORMS ......................................................................................... 5106 
APPENDIX L: NEUROLOGICAL TESTING .................................................................................................... 6107 
NIH Stroke Scale .................................................................................................................................. 6107 
Modified Rankin ................................................................................................................................... 9110 
APPENDIX M:  HOME DISCHARGE CHECKLIST ..................................................................................... 10111 
APPENDIX N:  QUALITY OF LIFE QUESTIONNAIRES ............................................................................ 11112 
Minnesota Living With Heart Failure Questionnaire ..................................................................... 11112 
Kansas City Cardiac Quality of Life Questionnaire ........................................................................ 13114 
APPENDIX O: HEART FAILURE ASSESSMENTS ....................................................................................... 17118 
NYHA Classification ....................................................................................................................... 17118 
ACC/AHA Stages of Heart Failure .................................................................................................. 17118 
APPENDIX P:  SIX MINUTE HALL WALK ................................................................................................... 18119 
APPENDIX Q:  CARDIOPULMONARY EXERCISE TESTING OVERVIEW .......................................... 20121 
APPENDIX R:  STUDY SUMMARY ................................................................................................................. 22123 
APPENDIX S:  BIBLIOGRAPHY ...................................................................................................................... 30131 
APPENDIX T:  CLINICAL STUDY AGREEMENT TEMPLATE ................................................................ 33134 
APPENDIX U:  INFECTION CONTROL GUIDELINES ............................................................................... 34135 
APPENDIX V:  INVESTIGATIONAL PLAN REVISIONS ............................................................................ 41142 

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LIST OF TABLES 
 
Table 1  C-Pulse® System Components ......................................................................................... 14 
Table 2. Follow–up Windows ....................................................................................................... 26 
Table 3.  Data Collection Summary ............................................................................................... 27 
Table 4.  Neurological Testing Collection Schedule ...................................................................... 32 
Table 5. Unavoidable Events .......................................................................................................... 47 
Table 6. Investigator Reports ........................................................................................................ 73 
Table 7. Sponsor Reports .............................................................................................................. 74 

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Trial Contact Information 
 
Sponsor & Distributor 
Sunshine Heart, Inc. 
12988 Valley View Rd 
Eden Prairie, Minnesota 55344 
Tel: 952 345 4200 
Fax: 952 224 0181 
www.sunshineheart.com 
Primary Contact: Aleela Baune 
Chief Executive Officer 
Dave Rosa 
12988 Valley View Rd 
Eden Prairie, Minnesota 55344 
Tel: 952 345 4200 
Fax: 952 224 0181 
Dave.Rosa@sunshineheart.com 
Sponsor’s Medical Director 
William Peters, MD 
CTSU 
Auckland City Hospital 
Park Rd, Grafton, New Zealand 
william.peters@sunshineheart.com 
National Co-Principal Investigator 
Cardiothoracic Surgeon 
Patrick M. McCarthy, MD 
Chief, Division of Cardiothoracic Surgery 
Northwestern University Feinberg School of Medicine 
pmccart@nmh.org 
National Co-Principal Investigator 
Heart Failure Cardiologist 
William Abraham, MD 
Chief, Division of Cardiovascular Medicine 
Ohio State University 
William.Abraham@osumc.edu 
Manufacturer 
Sunshine Heart, Inc. 
12988 Valley View Rd 
Eden Prairie, Minnesota 55344 
Tele: 952 345 4200 
Fax: 952 224 0181 
www.sunshineheart.com 
Clinical/Technical Support Hotline 
1-877-742-7857 (1-877-SHCPULSE) 

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INTRODUCTION 
 
PURPOSE 
 
 
Sunshine Heart Inc. is sponsoring a prospective, multi–center trial to assess the safety and 
provide indications for performance of the Sunshine Heart C-Pulse® System (“C-Pulse®”). 
The purpose of the study is to determine whether use of C-Pulse® as treatment for patients in 
moderate to severe heart failure (HF) is associated with reasonable assurance of safety and 
performance, such that the C-Pulse® merits Food and Drug Administration (FDA) approval 
for continuation into a pivotal study to examine the safety and efficacy of C-Pulse® for US 
market approval. 
 
STUDY SIZE AND DURATION 
 
 
This clinical study is expected to commence September 2008. The duration of the study is 
expected to be 120 months. The primary study population will include 20 patients 
enrolled and implanted with C-Pulse® in up to 7 centers in the United States (US) and 
potentially some Outside the United States (OUS) centers. This expansion protocol will 
allow 40 patients to be enrolled and implanted in up to 9 centers. The first 40 patients that 
meet all eligibility criteria will proceed to implantation. Up to approximately 60 patients 
will be enrolled and consented for performing screening and testing required to confirm 
eligibility, such as Computed Tomography (CT) scan. All patients must be consented 
prior to performing any study related procedures. A patient is considered enrolled upon 
signing the informed consent. To minimize the burden to the patient, data collected as 
standard of care and not for the specific reason for study eligibility may be used for 
baseline data points as outlined in the informed consent. These tests will suffice for the 
baseline dataset if collected within the screening timeframe of 30 days prior to implant. 
Only the patients who meet the eligibility criteria will proceed to implantation. All 
patients who do not meet the eligibility requirements will be promptly study exited. Study 
exit of these patients must be documented on the Study Exit form. The period of follow– 
up will be 6 months to assess the safety and performance before initiating the pivotal 
randomized clinical trial. All patients will continue to be followed annually during long 
term follow–up to a minimum of five years. 
The study will be conducted in accordance with Code of Federal Regulations (CFR) Parts 
11, 50, 54, 56 and 812. A progress report of the clinical outcomes will be prepared by the 
Data and Safety Monitoring Board (DSMB) following enrollment of the first five (5) 
patients and at least twice per year thereafter. The recommendation(s) from the DSMB 
may be circulated to each of the Investigation Review Boards (IRB) participating in the 
study upon request. 

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BACKGROUND 
 
 
Heart Failure (HF) represents a major and growing public health concern in terms of 
incidence, prevalence, morbidity, mortality and economic cost. Chronic HF is 
predominantly the result of ischemic heart disease or idiopathic dilated cardiomyopathy. 
Chronic HF is conventionally treated with drugs. However there are many circumstances 
where drug therapy is insufficient or where the heart has become refractory to drug 
therapy. Cardiac Resynchronization Therapy (CRT) is indicated in patients with HF who 
have ventricular dyssynchrony, commonly evidenced by a widened QRS complex. 
Resynchronization therapy is suitable for approximately 30% of moderate HF [(New York 
Heart Association (NYHA) Class III] patients, and has been shown to provide significant 
clinical improvement [as measured by NYHA Class, quality of life (QOL) score, 6 minute 
walk test, freedom from advanced heart failure treatments, etc.]1. However, as many as 
30% of patients who have CRT implants do not have a satisfactory response (“non– 
responders”). Further, many patients initially have a good response but then develop more 
advanced symptoms. 
Heart transplantation is an effective therapy for end stage NYHA Class IV patients. 
However, the number of donor hearts falls short of meeting the needs of patients and 
many patients are excluded because of age (the upper limit for transplant being 
approximately 65 years)2. 
Left Ventricular Assist Devices (LVADs) have been shown to offer the potential for the 
treatment of end stage NYHA Class IV HF patients. LVADs have been shown to improve 
survival in patients suffering severe HF and some LVADs have been approved as a bridge 
to transplant (BTT) and for destination therapy (DT). However, because of the blood– 
contacting nature, these devices have high associated risks such as bleeding, stroke, 
infection and device failure. Furthermore, despite prolonging life, patients spent more time 
in hospital due to these associated complications3. 
There is growing evidence that the unloading actions of LVADs can facilitate significant 
recovery and reverse remodeling of the heart4. However, there is a need for lower risk, 
lower cost devices that allow for long–term implant in less sick patients. Such a device 
could provide for partial unloading of the heart such that the patient can be weaned and for 
the device to not necessarily be removed. 
It is well established that a mode of circulatory support, known as counterpulsation, works 
by reducing the load on the heart, augmenting heart pump function, and increasing both 
coronary artery and total body blood flow. Unlike LVADs, counterpulsation devices act to 
 
 
 
 
 
1 [Abraham 2002] 
2 [Demers 2003] 
3 [Rose 2002] 
4 [Reinlib 2003, Birks 2006] 

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augment native heart function rather than to replace it. Whilst LVADs unload the heart, it 
is evident that they do not necessarily increase coronary artery blood flow5. 
Counterpulsation has 2 main benefits to heart function: 
• When the aortic valve is closed and the balloon is inflated, diastolic pressure is 
increased (“diastolic augmentation”): there is augmentation of flow into the 
peripheral arteries from the aorta, and particularly to the coronary arteries 
• Following the electrical excitation of the left ventricle [electrocardiogram (ECG) 
QRS complex], the heart contracts and the balloon is deflated. The reduction in 
impedance reduces aortic pressure and thus the work load of the heart by reducing 
the pressure–head which the heart has to eject against. This is termed "pre–systolic 
ventricular unloading" and allows the heart to contract more vigorously and with 
greater efficiency. 
Counterpulsation has been widely used the past 30 years for short term (2 to 7 days) 
cardiac support in patients with hemodynamic compromise but in whom recovery can be 
expected, such as after heart surgery or after a major heart attack. These intra–aortic 
balloons (IABs) are widely used in hospitals. The IAB is inserted via a femoral artery and 
positioned in the descending aorta. The IAB is attached to a bedside module that inflates 
and deflates the device based on the R wave of the ECG signal. When the condition of the 
heart has improved the IAB is removed. IAB counterpulsation a) increases coronary blood 
flow, b) reduces ventricular afterload to reduce the workload of the left ventricle, and c) 
increases cardiac output. 6 The level of counterpulsation may affect cardiac performance 
in the short–term: Cohen et al showed in a limited study of 20 patients a significantly 
higher velocity time integral across the Left Ventricle (LV) outflow tract resulted when 
counterpulsated at 1:1 versus 1:8. They did not show any difference with varying the 
balloon volume from 40 to 32 cubic centimeters (cc)7. 
The beneficial effect of counterpulsation in short term situations has stimulated interest in 
its potential effects when used in longer term situations. Long term counterpulsation may 
chronically reduce the load on the heart and augment the native heart blood pumping 
capacity. The devices can be turned on and off as required, particularly if the heart 
recovers its strength following months of support. Specific examples of investigational 
long term counterpulsation therapies include the CardioVAD device and a technique 
known as Aortomyoplasty. Ambulatory IAB (positioned via a graft in the axillary artery) 
has also been used to support patients as a bridge to transplant8. 
The CardioVAD (LVAD Technology, Inc., Detroit, MI) comprises a pump sewn into the 
wall of the descending aorta, an access device to allow a gas tube to pass through the skin, 
and a driver unit worn by the patient to move air into and out of the pump. The 
CardioVAD has been implanted in a limited number of patients in Class IV heart failure in 
 
 
 
5 [Ootaki 2005] 
6 [Cochran 2002, Cheung 1996, Reichart 1993] 
7 [Cohen 1995] 
8 [Cochran 2002] 

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an Investigational Device Exemption (IDE) Feasibility trial in the USA. Results of the 
trial to date have shown that the CardioVAD can significantly improve blood flow through 
the body and reduce HF symptoms9, though there is a significant surgical risk due to the 
invasive nature of the surgery. 
Aortomyoplasty involves surgically wrapping a muscle from a patient’s back around the 
outside of the aorta and electrically stimulating that muscle to contract in counterpulsation 
with the patient’s heart rhythm using a pacemaker–like device. The results of a series of 
15 patients have shown substantial benefits in heart pumping capacity compared to pre– 
operative measurements, improvement in patient well-being, and an excellent long–term 
(up to 8 years follow up) safety profile10. However, this procedure is associated with a 
significant surgical risk and lengthy rehabilitation period since the back muscle must be 
trained over a period of at least 6 weeks before there is effective counterpulsation. 
The current need is for a counterpulsation device or method that is effective enough to 
make its application appealing as a long–term implant to a large number of patients and 
physicians. It must be simple and safe, with a straight–forward implant procedure, and 
with long–term measurable patient benefits. Further, it would be advantageous for the 
counterpulsation device to be smaller, easier to insert, ambulatory, disconnectable, and not 
in the bloodstream. Such a device may be more readily adopted by a wider group of 
cardiologists and surgeons, and be suitable for a wider group of people in NYHA Class III 
or IV heart failure. It is important to point out that a counterpulsation device is aimed to 
augment native heart function and is fundamentally different from total artificial hearts, 
left ventricular assist devices and heart transplants which are meant to be a total 
replacement or an alternative to the native heart. Thus, the counterpulsation device is 
considered non–obligatory and not life–supporting. 
Sunshine Heart, Inc. has proposed C-Pulse®, a novel ambulatory, non–obligatory, non– 
blood contacting extra–ascending aortic counterpulsation system. The C-Pulse® System is 
designed to be implanted without the need for cardiopulmonary bypass or extensive 
dissection, to be able to be activated immediately, to augment heart function in a safe 
manner and to provide sustained relief from heart failure symptoms. It can be turned off 
safely, and similarly, in failure modes, is considered to have an associated low risk of 
death or disability, other than the recurrence of heart failure symptoms. C-Pulse® is not an 
alternative to the heart, it is an augmentation device, and it does not preclude the use of 
therapies that provide full circulatory support such as heart transplantation or LVADs. 
The C-Pulse® System consists of a counterpulsation Cuff secured around the outside of the 
ascending aorta, the main blood vessel out of the heart. The Cuff and a heart signal 
sensing wire are attached to an external driver. The external Driver inflates and deflates 
the Cuff in sequence with the ECG signal to assist heart function and improve the 
pumping capacity of the heart. The Cuff deflects the aorta in a “thumb–printing” manner 
which has been optimized to minimize aortic wall strain and maximize blood volume 
displacement per beat. The C–Pulse® System is non–blood contacting, simple to insert, 
and can be turned on and off as required; all natural blood pathways are maintained – there 
 
 
9 [Jeevananddam 2001] 
10 [Tranini 2002] 

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is no exposure of foreign material to the bloodstream. See Appendix E for a summary of 
experience to date with C–Pulse®. 

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C-P ULSE DEVICE DESCRIPTION 
 
THE SUNSHINE HEART C–PULSE® ICP SYSTEM 
 
 
The C-Pulse® ICP utilizes an “extra–aortic” inflatable Cuff which is surgically implanted 
around the ascending aorta, thus a) avoiding blood contact, and b) allowing the device to 
be both ambulatory and non–obligatory, for long–term cardiac assistance. Furthermore, 
counterpulsation on the ascending aorta is more efficient than the descending aorta 
position because 1) the blood displacement is “unidirectional,” and 2) diastolic and pre- 
systolic pulse wave propagations versus cardiac systole are better matched11 12. In 
addition, the ascending aorta is of a predictable helical shape13 14, has a large capacitance, 
no branches and presents a minimal risk of disease15. The implanted Cuff is inflated by the 
external battery powered pneumatic Driver and timing is coordinated to the R wave of the 
ECG. A standard implantable cardiac pacemaker lead is used with the system. A separate, 
exchangeable, wire–wound percutaneous interface lead (PIL) is implanted to connect the 
gas line of the Cuff and the ECG Sense Lead to the Driver. 
The C-Pulse® ICP has been designed to have a simple, highly reliable implantable 
component (the Cuff) and external wearable components (the Drive Unit and Battery 
Carrier) which are connected by means of a Percutaneous Interface Lead (PIL). A standard 
epicardial pacemaker lead serves as the ECG Sense Lead. The Driver is programmable by 
a physician using a Programmer via infra–red (IR) connectivity. 
The modular design of the C-Pulse® is shown in Figure 1. For the IDE study, the patient 
will be provided with two (2) each of the Drive Unit and Battery Carrier. The 
Percutaneous Lead is designed to facilitate simple surgical replacement of this component, 
in the case of untreatable skin infections at the exit site or damage to the patient connector. 
Figure 1 IDE C-Pulse System 
 
 
 
11 [Furman 1971] 
12 [Davies 2005] 
13 [Misfeld 2004] 
14 [Peters 2006] 
15 [Takasu 1992] 

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Key components of the C-Pulse system are outlined in Table 1Table 1. 
Table 1 C-Pulse® System Components 
SHC implantable Cuff: 
• Simple, less invasive surgery 
• No cardiopulmonary bypass 
• 3 sizes to fit ascending aorta outside diameter 29–40 millimeter (mm) 
• Non–blood contacting 
SHC Percutaneous Interface Lead: 
• 5 mm outside diameter 
• Silicone with ECG wire re-enforcements 
• Transmits air/ECG/heart sounds 
• Patient connector (with water–tight cap) 
• Lead is exchangeable 
• Home care package including supplies for dressing changes 
SHC wearable/portable Drive Unit and Battery Carrier: 
• Detachable, approx. 2.5 kilogram (kg) (total weight, split between Driver and 
Battery Carrier) 
• Ergonomic design 
□ wear in a vest or carry in a bag 
□ simple patient interface – on/off button and battery indicator 
□ visual and audible alarms 
• 4 hour battery life; single battery – recharge separately or in Battery Carrier 
• 1.4 meter (m) Driver cable with Isolation Module 
• Physician programmer 
□ Infra–red functionality 
□ Intuitive interface for setting counterpulsation functions 
□ Discrete “verification” button on Driver to accept Programmer changes 

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SYSTEM FEATURES 
 
 
C–Pulse® Allows Ambulation 
It is vital for a device intended to restore a heart failure patient quality of life that the 
device can allow the patient to ambulate and to be discharged home. The C-Pulse® Driver 
and Battery Carrier can be worn on a belt as a harness – the Battery Carrier and Driver are 
of approximately equal weights which allows even and ergonomic distribution of weight. 
A single long-life battery is used and is easily exchanged and re–charged. The Driver and 
Battery Carrier can be alternatively placed into one small carry–bag, for carrying over the 
shoulder. The Driver has a 1.4m cable that allows the Driver to be comfortably used in 
bed or when the patient is showering, and which can be coiled up and stored on the Driver. 
To avoid twisting in the line, the cable can be disconnected to coil it appropriately. 
Non–blood contacting 
The non–blood contacting feature of the C-Pulse® is unique for mechanical circulatory 
support devices.  No foreign body material is in the blood stream and thus the risk of 
blood clotting within the device mechanism is eliminated. There is no requirement for use 
of anti–coagulants for C-Pulse® use. 
Non–obligatory 
The non–blood contacting feature of C-Pulse® also allows the device to be intermittently 
turned off as tolerated. This allows the patient freedom for personal hygiene and 
convenience. The non-obligatory feature of C-Pulse® is essential in improving the 
patient’s quality of life and safety, however, the Device is expected to be used greater than 
80% of the time during the trial period. During the trial period, patient must not 
disconnect for longer than 15 minute intervals for a maximum of 4 hours daily (80% 
usage). The Driver records usage. 
 
INDICATIONS FOR USE AND INTENDED USE 
 
 
The C-Pulse® System is indicated for use in patients with moderate to severe heart failure 
[American College of Cardiology/American Heart Association (ACC/AHA) Stage C; 
NYHA Class III/IV], who are refractory to optimal medical therapy. The C-Pulse® 
System is intended to relieve the symptoms of heart failure, improve quality of life and 
cardiac function. The C-Pulse® System is also indicated for use in patients who are non 
responders to CRT pacemaker therapy. It is intended for use in hospital and at home. It is 
not intended as a replacement for heart function; it is not life sustaining or life–supporting 
therapy. It does not preclude the use of other heart failure therapies, such as valve 
surgery, heart transplantation or LVAD. 
 
SUMMARY OF IMPLANT PROCEDURE 
 
 
The C-Pulse® Cuff and Sense Lead are implanted through a chest incision and without the 
use of cardiopulmonary bypass. Only a small pericardiotomy is required, limiting the 

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potential for bleeding and for post–operative adhesions. The ascending aorta is isolated 
and its circumference measured. The circumferential length is marked on the Cuff and the 
Cuff is wrapped around the aorta such that the inflating aspect of the Cuff is positioned on 
the outside curvature. The Cuff is then checked to fit the aorta conformably and that the 
circumferential marks are appropriate prior to securing of the wrap with sutures. 
Interrupted ‘mattress’ sutures are recommended, placed with the Cuff ‘open’ and using the 
circumferential marks as guidance, and such that the inflation chamber of the Cuff is 
always visualized. A bipolar ECG Sense Lead is placed on the heart and the gas line of 
the Cuff and ECG Sense Lead are attached to the intra–corporeal “Y– connector” end of 
the Percutaneous Lead.  The Percutaneous Lead is then tunneled out over the abdomen, 
the extra–corporeal end of the Lead having a Patient Connector permanently attached. 
Alternatively, the Percutaneous Lead may be tunneled retrograde and secondarily attached 
to the gas line and sense lead. The Percutaneous Lead is designed to be exchanged or 
removed if required, the latter eliminating the exit site. If removal occurs, the Cuff and 
Sense Lead will remain within the thorax with the gas line of the Cuff and the connector 
of the Sense Lead capped off and accessible with minimal surgery in the subcutaneous 
tissue of the abdominal area. 

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STUDY DESCRIPTION 
 
DESIGN 
 
 
The study is designed to assess the safety and potential benefit of the C-Pulse® System 
before initiating a wider randomized clinical trial to demonstrate safety and effectiveness. 
The effect of the C-Pulse® system in relieving heart failure symptoms in patients with 
ACC/AHA Stage C, NYHA Class III-ambulatory Class IV heart failure will be 
documented with this study. 
This Feasibility Study is multi-center study which is being expanded to include up to 9 
centers in the US and potentially some OUS centers. The study population will be 
expanded to include 40 patients enrolled and implanted with the C-Pulse® System. The 
period of follow-up for the initial 20 patients will be 6 months to assess the safety and 
performance before initiating the pivotal clinical trial. It is desired that the system be used 
all the time.  However, the System should not be “Off” for greater than one hour at any 
one time for a maximum of four hours total per day during the study period.  For the 
extent of the trial period (6 months), C-Pulse ®should be used at least 20 hours per day 
(i.e. device must be used greater than 80% of the time).  The patient must limit the 
duration of disconnection to 15 minute intervals for a maximum of 4 hours total during the 
trial period to ensure the device is used for 80% of the time. The Driver logs patient usage 
automatically and stores into the system files. 
Patients will be followed for up to 10 years or until the study is closed. 
If a patient undergoes anesthesia for the purpose of C-Pulse implantation but does not 
receive a C-Pulse System, the patient will be followed until 30 days or discharge 
whichever occurs first. 
 
 
Baseline 
Inclusion/Exclusion 
≤ 30 Days 
 
Implant 
1, 3, and 6 
month 
Follow-up 
Long term Follow-up 
12 and 18 month – 
annually thereafter 
 
 
Figure 1A. Study Design 
Patients will be enrolled into the trial upon providing informed consent. Procedures 
related directly to the study must not be performed prior to informed consent. Data 
collection will be noted prior to implantation of the device and at one, three, and six 
months following implant and then long term at 12 and 18 months followed by annually 
post–implant for five years. Adverse events will be collected throughout the study until 
study closure and will be adjudicated by the Clinical Event Committee (CEC). 
Progress reports of the clinical outcomes will be reviewed by the DSMB after enrollment 
of five (5) patients and twice per year thereafter, unless slow enrollment does not warrant 
this meeting frequency. 

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Progression to the Pivotal study will be based on the assessment for safety of the device 
and indicators of performance. Baseline and follow–up data will be used to assess any 
significant difference in quality of life and functional variables pre and post implant and to 
assess the effect of counterpulsation. 
Following successful completion of this Feasibility Study, a pivotal study will be 
conducted to examine the safety and efficacy of the C-Pulse® system in patients in 
moderate to severe heart failure. The pivotal trial is expected to measure the same 
variables as the Feasibility Study. 
The total duration of the Feasibility Study is expected to be approximately 120 months or 
until the study is closed. 
 
OBJECTIVES 
 
 
Primary Objectives 
Following are the primary objectives for this study. The primary objective of the C-Pulse 
feasibility study is to assess safety, while at the same time obtain performance data for 
evidence of efficacy to assist planning for a pivotal study. Refer to the section on 
Statistical Methods and Data Analysis for a detailed discussion of the definitions and 
methodology. 
The Clinical Investigation shall: 
1. Assess the risks with regard to the performance of the device as defined by the 
serious adverse event rates, under normal conditions of use. 
2. Assess the potential benefits of C-Pulse as defined by improvements in Peak VO2, 
hemodynamic measures, quality of life and HF symptoms. 
Secondary Objectives 
Secondary objectives are intended to provide additional information on patient response 
and device performance and to allow planning for the pivotal study. The secondary 
objectives are as follows: 
1. Further assess the potential risks with regard to the performance of the device as 
defined by the device failure rate, adverse event rates, adverse event attribution, re- 
hospitalization rates, duration of support, and length of time to hospital discharge. 
2. Further assess the potential benefits of C-Pulse as defined by improvements in 
quality of life, fatigue impact scales, hemodynamics, average distance walked in 
the 6 minute hall walk test, and blood tests. 
3. Assess the device usage. 

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Together the primary and secondary objectives will: 
1. Allow refinement of clinical and physiological criteria for patient selection and 
refinement of protocols for the operative procedure and concomitant medical 
therapy and rehabilitation post-operatively – the results of the Feasibility Study 
will allow effective planning of a larger study to examine device efficacy 
2. Develop predictors for adverse events and measures for minimizing the frequency 
and/or severity of such events 
3. Determine the parameters of implantation, patient recovery, hospitalization, 
rehabilitation and home discharge 
4. Determine the means to design a successful pivotal trial in regards to the 
anticipated randomization, feasibility of blinding, core lab procedures and data 
collection 

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PATIENT SELECTION 
 
 
Inclusion Criteria 
Patients of both genders who satisfy all inclusion and exclusion criteria are eligible for this 
clinical study. Patients must meet the following criteria: 
1. Patient has ACC/AHA Stage C heart failure and remains in NYHA Class III - 
ambulatory Class IV despite optimal medical therapy. Patients must have stable, 
evidence–based optimal medical therapy for heart failure as defined below: 
• ACE inhibitor or ARB (Angiotensin Receptor Blocks) at least 30 days 
preceding implant or nitrate/hydralazine at the investigators discretion 
• Beta–blocker for at least 90 days and stable for 30 days preceding implant 
Note: Stable is defined as no more than a 50% reduction or 100% increase in 
the medications listed above. Transition within a therapeutic class is allowed if 
the dose is equivalent. 
2. Patient has left ventricular ejection fraction (LVEF) ≤ 35% 
3. Patient has had Cardiac Resynchronization Therapy (CRT) for at least 90 days 
prior to enrollment or is not indicated for a CRT device 
4. Patient has had an implanted cardio–defibrillator (ICD) at least 30 days prior to 
enrollment or is not indicated for ICD implantation. 
5. Patient is at least 18 years of age and not older than 75 years 
6. Patient six minute hall walk assessment between 100–350 meters 
7. Patient understands the nature of the procedure, is willing to comply with 
associated follow–up evaluations, and provide written informed consent prior to 
the procedure 
Exclusion Criteria 
Candidates must be excluded from the study if any of the following are met: 
1. Patient has any evidence of: 
o Ascending aortic calcification on posterior–anterior or lateral chest x–ray at 
initial screening 
OR 
o Atherosclerotic ascending aortic disease, specifically intimal thickening 
greater than 3mm or mobile atheroma (moderate) or mural calcification 
(severe) as detected by CT scan or echocardiography (Echo) 16 
 
 
 
 
16 [Davila–Roman 1999] 

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2. Patient has ascending aorto-coronary artery bypass grafts, history of aortic dissection, 
Marfans disease or other connective tissue disorder or has had an aortic root 
replacement 
3. Patient aorta not conforming to specified dimensional constraints defined by CT scan, 
most specifically mid ascending aortic outside diameter less than 29mm or greater 
than 40mm 
4. Patient has severe mitral valve incompetence, grade 4+ 
5. Patient has moderate to severe aortic valve incompetence, grade 2–4+ 
6. Patient has systolic blood pressure less than 90 or greater than 140 mmHg 
7. Patient has a Serum Sodium less than 130 mEq/L 
8. Patient has an Estimated Glomerular Filtration Rate (GFR) less than 40 ml/min/1.73m2 
9. Patient has any two of three of Bilirubin, Aspartate Aminotransferase (AST), Alanine 
Aminotransferase (ALT) greater than three times upper limit of normal for each 
institution 
10. Patient has a serum Albumin less than 3.0 g/dL 
11. Patient has Body Mass Index (BMI) less than 18 or greater than 40 kg/m2 
12. Men with Peak Oxygen Uptake (VO2) of greater than 18 ml/kg/min or less than 10 
ml/kg/min 
OR 
Women with Peak VO2 of greater than 16 ml/kg/min or less than 9 ml/kg/min 
13. Patient has any active infection 
14. Patient has had a myocardial infarction (MI), stroke, transient ischemic attack (TIA), 
cardiac or other major surgery, in the 90 days prior to study enrollment 
15. Patient has severe Chronic Obstructive Pulmonary Disease (COPD) as evidenced by 
Forces Expiratory Volume (FEV1) less than or equal to 0.9 L/min 
16. Patient requires a concomitant surgical procedure [i.e. coronary artery bypass graft 
(CABG), Valve repair] 
17. Patient is supported with a left ventricular assist device or intra–aortic balloon pump 
18. Severe Right Heart Dysfunction with systemic venous congestion evidenced by 
clinical signs/symptoms such as Central Venous Pressure (CVP) ≥ 20 mmHg, Cardiac 
Index (CI) < 2.0 l/min./m2, elevated liver function tests beyond three time the upper 
limit of normal and presence of ascites 
19. Patient has reversible causes of heart failure that may be remedied by conventional 
surgery or other intervention 
20. Patient is pregnant; Note: Negative pregnancy test required in all women of child 
bearing potential 

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21. Patient has any other condition that, in the opinion of the investigators, would 
disqualify the patient for inclusion in the study, limits survival to less than one year, or 
not permit valid consideration 
22. Patient is currently enrolled or has participated in the last 30 days in another 
therapeutic or interventional clinical study that is likely to confound study results or 
affect study outcome 
23. Patient has symptomatic Carotid artery disease or asymptomatic disease with a 
stenosis greater than 70% as determined by Carotid Doppler Ultrasound 
 
INVESTIGATIONAL CENTER INFORMATION 
 
 
Number of Sites 
It is intended that up to 9 centers in the US and potentially some OUS centers will 
participate in this clinical evaluation. 
Investigator Agreement/Financial Disclosure 
An Investigator Agreement along with a Financial Disclosure Form must be signed by the 
investigator and returned to Sunshine Heart, Inc. and/or designee before commencement 
of the study at a clinical site. 
Curriculum vitae including the investigator’s current position and title will also be 
required from each investigator and co–investigator(s) participating in this study. 
Investigational Review Board 
Investigational Review Board approval of the clinical study must be received and the 
contents of the approval letter approved by Sunshine Heart before commencement of the 
study at a clinical site. Required contents are as follows: 
• Name of study 
• Name/address of IRB 
• Date of approval 
• Sufficient identification of version/date of the Protocol, amendments and Informed 
Consent 
• An IRB member list or ID number must be provided to Sunshine Heart 
Access to Center and Study Materials 
The investigator(s) or his/her delegate(s) and the study coordinator(s) must be accessible 
to the Sunshine Heart monitoring staff or designee and Clinical Team. This accessibility 
is of particular importance for completing and/or correcting the data provided. For the 
study monitors, access to the patient records for source data verification will need to be 
granted and prepared prior to the monitoring visit. 

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Confidentiality 
All information generated during the trial is considered highly confidential and must not 
be disclosed by any method to persons not directly involved in the trial without prior 
consent from the sponsor or sponsor designee. 
Attending Investigator Meetings or Conference Calls 
Investigator and/or study coordinator meetings or conference calls may be held to discuss 
the study protocol, device training, study data or other aspects of trial progress and 
management. Interim meetings or teleconference calls will be organized as needed to 
discuss relevant study issues. The investigator must agree to attend these meetings and/or 
conference calls or send a co–investigator if they are unable to attend. 
Required Equipment 
The following study equipment will need to be available at each center to support the 
implant and follow–up of the C-Pulse® System: 
• The C-Pulse® ICP System 
• Standard cardiac surgery required equipment and facility 
• Echocardiography equipment 
• CT Scanning equipment 
• Cardiopulmonary Exercise equipment 
Supply of Study Materials and Device Accountability 
All investigators will receive the investigation plan, case report forms, and study 
agreement documents. 
Sunshine Heart’s clinical affairs department will control the supply of investigation 
devices, software, and administrative forms necessary to conduct and administer the study. 
A limited amount of investigational product will be distributed to designated Sunshine 
Heart field personnel and to approved investigators. A site must be approved to store 
equipment at their center. Approval will require the center to have made provisions for 
strict control of the investigational devices. 
A Device & Equipment Disposition Log shall be maintained at each center to track 
investigation product information including, but not limited to, the model, serial number 
of each investigational product and the date used. Completed System Implant and Implant 
Equipment Case Report Forms and Device & Equipment Disposition Logs will be 
reviewed as part of the device tracking and ongoing site monitoring. Based upon return 
and review of these forms, additional clinical product will be supplied to the respective 
investigators within prescribed study limits. Labeling is packaged with each device. 
Criteria for Early Termination or Suspension 
Reasons for possible suspension of a clinical investigator or a clinical center from 
enrollment of further patients may at the sponsor’s discretion include but are not limited to 
the following: 

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• Failure to obtain informed consent 
• Non–compliance to the inclusion/exclusion criteria 
• Failure to follow through with Investigational Review Board (IRB) for approval or 
continuation of the clinical study 
• Inadequate device tracking or off–label investigator device use 
• Failure to follow–up patients per scheduled follow–ups 
• Failure to submit data in a timely manner 
• Failure to follow–up with findings on a monitoring report 
Note that any patients previously enrolled will continue to be to be followed at this 
institution by the investigator or a named co-investigator. 
 
Laboratory Accreditation and Normal Values 
Before initiation of the study, appropriate accreditation for all laboratories to be used in 
the study must be provided to the sponsor. Throughout the study, the Investigator must 
provide documentation of all renewals of accreditation. The ranges of values considered 
normal for the laboratory tests being performed for the study must be provided to Sponsor 
in order to facilitate pooling of the data. 
 
PROCEDURES 
 
 
Screening and Patient Informed Consent 
Prior to enrolling patients, each investigational center IRB will be required to approve the 
study Investigation Plan, and the Patient Informed Consent. In addition, patients will be 
required to provide written informed consent for enrollment. A Screening Log is located 
within the site Regulatory Binder and should be completed for all patients screened but 
not enrolled for the study. 
Patients will undergo a pre–implant baseline assessment to ensure they meet the inclusion 
and exclusion criteria no more than 30 Days prior to the implant date. Patient informed 
consent must be signed prior to conducting any screening or baseline testing procedure 
performed for study purposes. When a patient signs an informed consent for the  
study, he/she is considered enrolled in the study and will be assigned a study 
identification number by the center. To minimize the burden to the patient, data 
collected as standard of care and not for the specific reason for assessing study eligibility 
may be used for baseline data points as outlined in the informed consent. These tests will 
suffice for the respective portion of the baseline dataset if collected within the pre-implant 
evaluation timeframe of 30 days prior to implant. Upon completion of screening, all 
patients that do not satisfy the eligibility criteria will be promptly study exited without 
proceeding to implantation. Study Exit of these patients must be documented on the Study 
Exit Form. Any patient whom undergoes anesthesia for the purpose of C-Pulse 
implantation but does not receive the device will be monitored for adverse events as 

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defined by the protocol for 30 days or discharge whichever occurs first. Any Sunshine 
Heart field personnel or designee present for the implant procedure should review the 
informed consent prior to the procedure to ensure compliance. 
In accordance with the ethical principles that have their origin in the Declaration of 
Helsinki, each patient must be informed about the study and the patient or legal 
representative must sign and date an agreement acknowledging that participation in the 
study is voluntary. The Patient Informed Consent Form will be provided to the patient in 
the language he/she is able to read and understand. (Refer to Appendix H for the sample 
Consent Form). The original signed Informed Consent will be retained in the individual 
Participant Study folders, and copies of the signed Informed Consent Form will be 
provided to the patient and to the hospital medical records of the patient. 
Patients shall be consented for follow–up to 10 years. 
Patient Withdrawal or Loss to Follow–Up 
In the event a patient chooses to withdraw from the clinical study, the investigational site 
should attempt to ensure that any adverse events are resolved and documented as such. A 
Study Exit/Death Form must be completed and the patient will no longer be followed in 
the clinical study. 
In the event the patient becomes lost to follow-up, the investigational site should make 
two documented attempts to contact the patient. A Study Exit/Death Form must be 
completed and the patient will no longer be followed in the clinical study. 
Data Collection Overview 
A review of patient files is required to determine preliminary eligibility according to 
patient inclusion and exclusion criteria. Baseline data including all imaging and 
functional test must be collected no more than 30 days prior to the implant date. 
Follow–up data will be collected at the time of implant, hospital discharge, at planned 
follow–ups (1-month, 3-month, 6-month, 12-month, 18-month and annually from the 
implant date thereafter), and “unscheduled” follow–ups (device testing, patient symptoms 
requiring re-hospitalization, etc.). All adverse events will be collected throughout the 
study until closure. 
Data will be collected via electronic data capture (EDC) screens referred to as e-case 
report forms (eCRFs). Echocardiogram tapes, and digital storage media must be 
documented in the patient medical record for source documentation. 

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The table below outlines the data collection with the appropriate time windows. 
 
Table 2.  Follow–up Windows 
Evaluation 
Time Window 
 
Pre–Implant Evaluation 
No more than 30 days prior to implant 
Implant 
Day 0 – Implant 
Pre-Discharge 
Within 36 hours prior to discharge 
1–month follow–up 
Days 30 ± 7 Post–Implant 
3–month follow–up 
Days 90 + 14 Post–Implant 
6–month follow–up 
Days 180 ± 30 Post–Implant 
12-month follow-up 
Day 365 ± 60 Post-Implant 
18-month follow-up 
Day 540 ± 60 Post-Implant 
Annually Post-Implant 
Years 2, 3, 4, 5, 6, 7, 8, 9 and 10 Post Implant 
(± 60 days of anniversary) 
 
Testing should be conducted at the investigational site. The data collection criteria are 
summarized in Table 3. 

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Table 3.  Data Collection Summary 
 
Follow-up Requirements Baseline to 6 months Post Implant 
Pre- 
Implant 
Implant 
Pre- 
Discharge7 
1 mo 
3 mo 
6 mo 
A. PATIENT ELIGIBILITY 
X 
B. GENERAL 
Demographic Data 
X 
Medical History 
X 
General Physical Examination 
X 
X 
X 
X 
X 
X 
Concurrent Medications 
X 
X 
X 
X 
X 
X 
Pregnancy test (if applicable) 
X 
C. VITAL PARAMETERS 
Weight 
X 
X 
X 
X 
X 
Heart rate 
(ECG pre-implant) 
X 
X 
X 
X 
X 
Blood pressure 
X 
X 
X 
X 
X 
Respiratory rate 
X 
X 
X 
X 
X 
D. CARDIOPULMONARY 
CT aorta 
X 
X 
CXR 
X 
X 
X 
ECHO 
X 
X2 
X 
X 
X 
Right heart catheterization 
(CVP, PAP, CI, PCWP,SVR, PVR) 
X 
X 
Peak O2 uptake 
X 
X 
E. QUALITY OF LIFE 
NYHA Classification 
X 
X 
X 
X 
MLHF Score/ KCCQ 
X 
X 
X 
X 
Fatigue Impact Scales 
X 
X 
X 
X 
X 
Six Minute Walk 
X 
X 
X 
X 
F. HEMATOLOGY 
Hemoglobin 
X 
X 
X 
X 
X 
Hematocrit 
X 
X 
X 
X 
X 
Plasma free hemoglobin 
X 
X 
X 
X 
X 
Platelet count 
X 
X 
X 
X 
X 
White cell count 
X 
X 
X 
X 
X 
APTT 
X 
X 
X 
X 
X 
INR 
X 
X 
X 
X 
X 
Fibrinogen 
X 
X 
X 
X 
X 
G. BIOCHEMISTRY 
Serum sodium 
X 
X 
X 
X 
X 
Serum potassium 
X 
X 
X 
X 
X 
Serum creatinine/ GFR3 
X 
X 
X 
X 
X 
BUN 
X 
X 
X 
X 
X 
Serum albumin 
X 
X 
X 
X 
X 
Serum bilirubin 
X 
X 
X 
X 
X 
Serum ALT 
X 
X 
X 
X 
X 

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Follow-up Requirements Baseline to 6 months Post Implant 
Pre- 
Implant 
Implant 
Pre- 
Discharge7 
1 mo 
3 mo 
6 mo 
Serum AST 
X 
X 
X 
X 
X 
Serum BNP 
X 
X 
H. NEUROLOGICAL 
ASSESSMENT 
Neurological testing (NIHSS)4 
X 
X 
X 
X 
X 
Modified Rankin 4 
X 
X 
X 
X 
X 
Head CT 5 
X 
Neurological Consultation 
X 
X6 
I. IMPLANT DETAILS 
X 
J. DEVICE LOG 
X 
X 
X 
X 
K. DISCHARGE 
CHECKLIST 
X 
1 Annually post-implant 
2 Epi-aortic Echo at implant 
3 Estimated GFR at Baseline and within one week post CT to evaluate contrast induced nephropathy. 
4 Post Neurological Dysfunction AE – 30, 60 and 90 days post event 
5 At Baseline only or as clinically indicated with any Neurological Dysfunction AE – Head CT should be completed only after clearance 
for implantation 
6 Required at 5-7 days post ICU discharge or at hospital discharge whichever occurs first and at the time of any suspected Neuro 
Dysfunction AE 
7 At Discharge - within 36 hours prior and as close to discharge as possible (see Appendix M) 
 
 
Long-term Post Implant Follow-Up Requirements 
12 month 
18 month 
Annually 
Year 2-10 
A. PATIENT ELIGIBILITY 
B. GENERAL 
General Physical Examination 
X 
X 
X 
Concurrent Medications 
X 
X 
X 
Pregnancy test (if applicable) 
C. VITAL PARAMETERS 
Weight 
X 
X 
X 
Heart rate 
(ECG pre-implant) 
X 
X 
X 
Blood pressure 
X 
X 
X 
Respiratory rate 
X 
X 
X 
D. CARDIOPULMONARY 
ECHO 
X 
X 
X 
E. QUALITY OF LIFE 
NYHA Classification 
X 
X 
X 
MLHF Score/ KCCQ 
X 
X 
X 
Fatigue Impact Scales 
X 
X 
X 
Six Minute Walk 
X 
X 
X 
F. HEMATOLOGY 
Hemoglobin 
X 
X 
X 
Hematocrit 
X 
X 
X 
Plasma free hemoglobin 
X 
X 
X 

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Long-term Post Implant Follow-Up Requirements 
12 month 
18 month 
Annually 
Year 2-10 
Platelet count 
X 
X 
X 
White cell count 
X 
X 
X 
APTT 
X 
X 
X 
INR 
X 
X 
X 
Fibrinogen 
X 
X 
X 
G. BIOCHEMISTRY 
Serum sodium 
X 
X 
X 
Serum potassium 
X 
X 
X 
Serum creatinine/ GFR3 
X 
X 
X 
BUN 
X 
X 
X 
Serum albumin 
X 
X 
X 
Serum bilirubin 
X 
X 
X 
Serum ALT 
X 
X 
X 
Serum AST 
X 
X 
X 
J. DEVICE LOG 
X 
X 
X 
K. DISCHARGE CHECKLIST7 
 
Summary of Required Testing 
Testing information will be recorded on the appropriate eCRF (Appendix K). Required testing 
includes: 
Device Performance Parameters – (at all follow–up visits) 
Device performance parameters shall be retrieved after optimization following 
implantation on Day 0, at all follow–up periods and whenever there is an unscheduled 
visit accompanied by a change to any device parameters. Parameters to be recorded 
include: 
• Counterpulsation mode 
• Counterpulsation volume 
• Inflation slew rate 
• Deflation slew rate 
• Inflation hold pressure 
• Device usage log (patient should use device for a minimum of approximately 20 
hours per day) 
• Other Events (i.e. alarms and/or events logged into the driver system file) 
• Heart rate 
• Non-invasive sitting blood pressure must be recorded at the time of the device 
check. 

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Data will be downloaded from the driver. Data will be recorded on the Follow-up eCRFs 
and stored electronically. 
Echocardiographic Testing - (Baseline, 1, 3, 6, 12, 18 month, and annual follow–up visits) 
A transthoracic echocardiography test will be performed at Baseline and at the 1, 3, 6, 12, 
18 month and annual follow-up visits. A recording of the echocardiogram must be 
collected and sent to the Echo Core Lab for analysis. The Echocardiography 
measurements will include: 
• Left ventricular end-diastolic and end-systolic dimensions (diameters, areas and 
volumes) 
• Assessment of mitral, tricuspid and aortic valve function (regurgitation and 
gradient) 
• Right ventricular systolic pressure (with estimation of CVP) 
• Ejection Fraction and Myocardial Mass 
• LV diastolic function 
Data will be recorded on the Baseline and Follow-up eCRF. 
Epi-Aortic Surface Echo - (collected at implant) 
A surface ultrasound interrogation will be performed on the ascending aorta to confirm the 
absence of significant aortic disease. Confirmation of the absence will be recorded on the 
Implant eCRF. 
Right Heart Catheterization - (Baseline and 6 month follow–up visits) 
A right heart catheterization will be performed at Baseline and 6 month visit. The right 
heart catheterization should be performed using the thermal dilution method if possible 
with access via the subclavian or internal jugular (i.e. swan ganz). Data required from the 
procedure include: central venous pressure (CVP), systolic/diastolic/mean pulmonary 
artery pressure (PAP), Cardiac Index (CI), pulmonary capillary wedge pressure (PCWP), 
pulmonary artery pressure (PAP), systemic vascular resistance (SVR) and pulmonary 
vascular resistance (PVR). 
Data will be completed on the Baseline and Follow-up eCRFs – Appendix K. 
CT Scan - (Baseline and 6 month follow–up visits) 
An ECG gated 1–2 mm slice thoracic CT scan is required at Baseline, and at the 6 month 
visit. A recording of the CT Scan must be collected and sent to the CT Scan Core Lab for 
analysis of the Baseline and 6 month assessment. A contrast study should be completed 
for Baseline testing. A minimum contrast injection rate of 4 cc/sec is recommended. 
(Note: Protection of renal function is important. Please minimize the volume of 
contrast, ensure prehydration and use acetylcysteine.) 
A contrast study is not required for follow–up tests unless there is a concern there is 
extravasation of blood from the aorta. 
Data required from the procedure include: 

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• Sagittal and coronal images shall be reconstructed at mid–systole and mid–diastole 
to measure narrowest mid ascending aortic luminal dimensions (i.e. with Cuff 
inflated and deflated). 
Assessment will be made of the intima for the degree of atherosclerotic ascending aortic 
disease, specifically: Nil, Mild (intimal thickening less than or equal to 3 mm), Moderate 
(intimal thickening greater than 3mm or mobile atheroma) or Severe (mural 
calcification)17. The CT Scan Core Lab will assess the outcome of the test for 
acceptability. Data will be completed on the Baseline and Follow-up eCRFs. 
NOTE: Contrast-induced nephropathy must be evaluated within one week post-baseline 
CT scan. Patients with an increase in Creatinine ≥ 0.5 mg/dL or a greater than 20% 
reduction in GFR must be followed until resolution of the decrease in renal function. This 
will be tracked as an observation via the follow-up form and should not be reported as an 
adverse event. 
Neurological Assessment - (pre-implant, pre-discharge, 1, 3 and 6 month follow-ups) 
A series of tests/assessments are required to assess for the presence of neurological 
dysfunction. Outlined below is the required assessment tool and specific required interval 
for collection: 
 
NIH Stroke Scale and Modified Rankin 
NIH Stroke Scale (NIHSS) is the standardized assessment tool for screening for any 
unobserved neurological dysfunction. The Modified Rankin is a standardized 
assessment tool for scoring disability status and/or ability to function. The NIHSS and 
Modified Rankin are required at pre-implant, at pre-discharge, 1, 3 and 6 months post 
implant. In the case of a neurological dysfunction adverse event, the NIHSS and 
Modified Rankin are required at 30 and 60 days post event in addition to the regular 
follow-up schedule. Clinicians performing the NIHSS and Modified Rankin are 
required to be trained. Clinicians performing NIHSS must also be certified prior to 
performing the assessment. Access to required training and certification tools will be 
provided in the study activation training for the study personnel designated for 
collecting the NIHSS. A neurological consultation is also required if an increase of 2 
or more is noted on the NIHSS. 
 
Head CT Scan 
A standard CT scan of the head is required at pre-implant as a baseline measure 
immediately prior to device implant (but after study enrollment). In the case of a 
neurological dysfunction adverse event a CT scan of the head is also required as 
clinically indicated at the time of the adverse event. The scheduled baseline CT scan 
of the head should be completed only after the scheduled CT of the aorta – if the aorta 
does not meet inclusion criteria then he/she is not exposed to a further CT scan. 
 
 
 
 
 
 
17 [Davila–Roman 1999] 

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Standard Neurologic Consultation 
A neurological consultation is required within days 5-7 post ICU discharge or at 
hospital discharge whichever occurs first. A neurological consultation is also required 
if an increase of 2 or more is noted on the NIHSS and at the time of a neurological 
dysfunction adverse event. The neurologist must record the outcome from the 
consultation into the medical record per institutional requirements for source 
documentation and on the Neurological Exam eCRFs (see Table 4 below). 
 
Data will be completed on the NIHSS, Neurological Exam, Baseline and Follow-up eCRF. 
The table below highlights the neurological testing follow-up data collection: 
Table 4. Neurological Testing Collection Schedule 
 
Item 
Pre- 
Implant 
Post-ICU 
Discharge 
Neuro 
AE 5 
Post- Neuro 
AE Day 30, 
60, 905 
PID 
30 
PID 
90 
PID 
180 
Neurological 
Exam 1 
X 
X 
X 
Head CT2 
X 
X 
NIHSS3 
X 
X 
X 
X 
X 
X 
X 
Modified 
Rankin4 
X 
X 
X 
X 
X 
X 
X 
1- Performed by a neurologist after study enrolment and prior to implant. Collected on Neuro Exam eCRF. 
2- After study enrolment and prior to implant. Result collected on Neurological Exam eCRF and Neuro Dysfunction eCRF. 
3-Collected on the NIHSS eCRF. 
4- Collected on the Modified Rankin eCRF. 
5- Neuro Assessment and testing expected within 7 days post AE, between days 23-37 days post AE, between days 53-67 and between 
days 83-97 post AE. 
 
Laboratory Parameters and Hemodynamics - (Baseline, Pre-Discharge, 1, 3, 6, 12, 18 month and 
annual follow–up visits) 
A full listing of all required lab tests and hemodynamic measurements is included in Table 
3 above. 
Measurements must be done at Baseline, Pre-Discharge, 1, 3, 6, 12, 18 month visits and 
annually thereafter. 
Data will be completed on the Baseline, Pre-Discharge, and Follow-up eCRFs. 
Six Minute Hall Walk Test - (Baseline, 1, 3, 6, 12, 18 month, and annual follow–up visits) 
The patient must perform a six–minute hall walk test (6MHW) at Baseline, and at 1, 3, 6, 
12, 18 month visits and annually thereafter with the C-Pulse™. Detailed information is 
included in Appendix P. 

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A familiarization test is required, but may have been performed in the previous one–year 
prior to implant. Instructions for conducting a six-minute walk test are located in 
Appendix P. 
Data will be completed on the Baseline and follow-up eCRFs. 
Quality of Life Assessment - (Baseline, 1, 3, 6, 12, 18 month and annual follow–up visits) 
The patient must complete the Minnesota Living with Heart Failure Questionnaire 
(MLWHF) and the Kansas City Questionnaire (KCCQ) at Baseline, 1, 3, 6, 12, 18 month 
and annual visits. 
Copies of the questionnaires are included for reference in Appendix N. 
Data will be completed on the Baseline and Follow-up eCRFs. 
Fatigue Impact Scales - (Baseline, Pre-Discharge, 1, 3, 6, 12, 18 month and annual follow–up 
visits) 
The patient must complete the Fatigue Impact Scale and the Daily Fatigue Impact Scale at 
Baseline, Pre-Discharge, 1, 3, 6, 12, 18 month and annual visits. 
Data will be completed on the Fatigue Impact and Daily Fatigue Impact eCRFs. 
NYHA Class Assessment - (Baseline, 1, 3, 6, 12, 18 month and annual follow–up visits) 
A clinician at each site shall complete the NYHA Classification at Baseline, 1, 3 6, 12, 18 
month and annual visits. 
Data will be completed on the Baseline and follow-up eCRFs. Refer to Appendix O for 
detailed description of the assessment. 
Concomitant Medications (Baseline, 1, 3, 6, 12, 18 month and annual follow–up visits) 
All medications will be recorded on the Medication eCRF. Doses are required for all 
cardiac medications including diuretics. Heart Failure medications such as ACE inhibitors 
and Beta Blockers must remain stable through the six month study period. Upward 
titration is not permitted beyond the baseline equivalent dose. 
Cardiopulmonary (CPX) Testing - (Baseline and 6 month follow–up visits) 
Two CPX tests may be required pre–operatively: 
1) a familiarization test to allow the patient to become familiar with walking on a 
treadmill and with the breathing apparatus in his/her mouth and 
2) a baseline test. 
During the familiarization, the patient should exercise to his/her symptomatic maximum. 
If the patient reaches his/her maximum, this test will be considered the baseline test. 
The first test should be conducted prior to implant for baseline assessment. If a second 
test is required it should be conducted greater than 24 hours after the first. Note: If a 
patient has a documented CPX test within the past 6 months prior to implant, then this test 
will be considered the familiarization test. A baseline test will still be required prior to 
implant if not conducted within the past 30 days, but the familiarization can be skipped. 

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Follow up measurements must be taken at the 6 month visit. 
Please refer to Appendix Q for additional information on the testing procedure. A blinded 
independent core lab will evaluate the CPX test results. A recording of the CPX must be 
collected and sent to the CPX Core Lab for analysis. 
Data will be completed on the eCRF and via the electronic data stored on disk. 
Pre-implant Preparation 
When a patient signs the informed consent for the study, he/she is considered enrolled into 
the study. The patient informed consent must be signed prior to conducting any 
procedure/testing performed for study purposes. Any patient that does not meet the 
eligibility requirements will be promptly study exited. 
Pre-Implant Baseline Testing and Data Collection Summary 
The following pre–implant baseline data will be obtained 30 days prior to implant. These 
data will be used by the center to confirm inclusion and exclusion criteria are met. A 
complete reference list of tests and hemodynamics to measure is included in Table 3. 
• Inclusion and Exclusion Verified 
• Informed Consent Obtained 
• Medical History and Physical Exam 
• Echocardiogram 
• Chest X–ray 
• ECG 
• Right Heart Catheterization 
• Cardiopulmonary Exercise Testing 
• Six Minute Hall Walk 
• Fatigue Impact Scales 
• Cardiovascular Medications Documented 
• Cardiovascular Medical History Documented 
• CT Scans – Aorta and Head Documentation 
• Neurologic Assessment (Neurology Consult, NIHSS and Modified Rankin) 
• Quality of Life Questionnaires (MLWHF and KCCQ) 
• Baseline Hemodynamics 
• Serum Labs 
• NYHA Classification 
• Medications 
• All adverse events reported 

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Clinical Procedures – Implant through discharge 
The System Implant eCRF will be used to collect implant data. 
The hospitalization phase is divided into three major parts: (i) Prior to implant, (ii) Implant 
procedures, and (iii) Post–implant to discharge. 
Pre–Implant Considerations 
Medication Therapy 
Prescribed drugs are to be maintained until the time of surgery unless instructed otherwise 
by the anesthetist. Prophylactic anti–coagulation should be stopped. Premed given per 
institutional protocol. 
Cardiac Resynchronization Therapy (CRT) 
Per the eligibility criteria a patient should not be enrolled earlier than 90 days following 
CRT implant. Patients enrolled with a CRT device must have the Cardiac 
Resynchronization Therapy continued during the follow up period. ICD Therapy should 
remain activated except during the surgical implantation. 
Planning for Device and Percutaneous Tube Positioning 
Have the patient try on the Vest and bag to determine the best exit site. The goal is to 
minimize trauma to the exit site and to maximize patient comfort. Pay particular attention 
to the costal margins, belt line, and impact of sitting and standing and lying, and the exit 
site when wearing the Driver. The distance of the exit site from the costal margin should 
be considered in relation to the thickness of subcutaneous tissue, in order to prevent the 
percutaneous tube from rubbing against the costal margin. Also consider patients who 
inject insulin into the abdominal area. Mark the exit site. 
Antisepsis Prophylaxis 
Administer prophylactic antisepsis coverage. Recommended prophylaxis: 
• Vancomycin 15mg/kg IV one hour pre-op given over 30 minutes and with 
minimum 5 minute interval blood pressure monitoring or arterial line monitoring – 
note that Vancomycin can cause hypotension in this patient population and should 
not be given unsupervised pre-operatively on the ward. Follow–up doses Q12–24 
hr post-operatively for 48 hrs, guided by serum Vancomycin trough levels. 
• Keflex 1g IV one hour pre–op then Q8–12hr for 48 hrs 
• Rifampicin 600 mg PO 2hrs pre–op then daily for 2 days – stop if liver function 
tests become deranged greater than two times baseline 
• Nasal Bactroban application day prior to surgery 
Note: Record all drugs and doses on the Medication eCRF. 
Prepare and shave the patient: Pre-operative scrub with antiseptic (Septisol or 
Chlorhexidine) on the night prior to surgery then again the morning of the surgery, and 
clip and shave the surgical area prior to transport to the operating room. 

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Observe Operating Room precautions – particularly, limit the number of people in the 
room, and traffic in and out of the room. 
 
Baseline Procedures 
Baseline investigational procedures as above should have been completed and data 
collected into the System Implant and Medication eCRFs. 
 
Implant Procedure 
Note: Refer to the Instructions for Use (IFU) for the C-Pulse® Cuff, Percutaneous 
Interface Lead and C-Pulse® System, which outline device preparation, implantation, and 
operation. The IFUs may be found in Appendix F. 
 
Procedure Summary 
1. Establish intra-venous and intra-arterial lines (if not already established above). 
Insert central venous sheath and position right heart catheter (may be done 
following general anesthesia), and connect surface ECG. 
2. Induce general anesthesia: intubate with endotracheal tube and ventilate per 
routine. Blood gases, Hb, and Hct are monitored during surgery per routine. 
3. Recommended three–step approach to skin preparation: 
a. antiseptic scrub (Septisol or Chlorhexidine) 
b. alcohol, which is then allowed to dry 
c. Betadine gel, which is allowed to dry. 
Note: combination alcohol/Betadine preparation may be used 
4. Drape patient with steri-drapes (e.g. Ioban), over exposed prepared skin. 
5. Perform chest incision. 
6. Incise pericardium up onto ascending aorta, mobilize ascending aorta from 
pulmonary artery. 
7. Using umbilical tape, measure mid-ascending aortic circumference and record on 
System Implant eCRF. 
8. Use CT scan to select Cuff size per mid–ascending aortic outside diameter. 
9. Delay opening sterile packaging for the C-Pulse® Cuff, ECG lead and PIL until 
they are ready to be implanted. See IFU for details regarding opening and 
implanting the C–Pulse® Cuff and PIL, including Warnings and Precautions. 
10. Evacuate air from C-Pulse Cuff and mark circumferential lines for suturing. 
11. Massage antibiotic solution* into the flocking anchors and into the wrap. 
(*Gentamicin and normal saline 160g/L, or Vancomycin and normal saline 2g/L) 
12. Implant device about the aorta and secure according to the IFU. 
13. Open ECG lead sterile packaging when required. 

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14. Attach a bipolar epicardial ECG sensing lead to the RV or LV per IFU. 
15. Create exit site by excising skin button that is approximately 80% of the tube 
outside diameter. 
16. Secure Cuff and Lead and attach to intracorporeal aspect of PIL per IFU and track 
out under the costal margin through a curvilinear pathway, either superior or 
inferior to the umbilicus as it suits best, to the desired pre–determined exit site. A 
separate small incision may be needed to allow further tunneling of the Lead and 
gas-line to the intended exit site. The PIL may alternatively be tunneled from “out– 
to–in” and connected to the Cuff gas-line and ECG lead secondarily. 
17. The PIL at the exit site should be oriented horizontally or slightly downward to 
allow good natural drainage of the exit site. 
18. The flocking of the PIL should be positioned to be subcutaneous, approximately 2 
cm from the exit site. 
19. Verify device function: 
a. Test for adequate sensing of the R wave by the Driver with respect to 
beginning of LV systole per IFU. 
b. Optimize inflation/deflation and displacement volume. Gas inflation hold 
pressure should not exceed 50mmHg above the mean arterial pressure. 
See IFU C–Pulse® System (LBL 01918). 
20. Fill chest with saline, massage any trapped air from under the Cuff, and observe to 
ensure no air-leaks are visible. 
21. Inflate lungs fully to check percutaneous lines – gas–line and ECG lead may be 
immobilized at 1–2 other locations e.g. right anterior mediastinum, sub–costal 
incision. 
22. Check for hemostasis, irrigate with antibiotic solution. 
23. Insert mediastinal and any other drains as required, and close all wounds. 
24. Apply occlusive surgical dressings to all wounds and to immobilize the 
percutaneous tube. 
Post–Implant Considerations (prior to discharge) 
1. Patient taken to ICU – driver may be disconnected for transport. 
2. Ensure both Drivers are configured with the same settings and verify function of both as 
above. 
3. Extubate patient, when appropriate – move to the telemetry ward when appropriate. 
4. Chest and other drains should be removed as soon as practical, at the discretion of the 
surgeon, and typically within 48 hours, depending on drainage. 
5. Recommended atrial arrhythmia treatment for new atrial fibrillation with rate greater than 
110 beats per min: IV or oral amioderone loading and oral amioderone maintenance. 

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6.  Heart rates should be maintained below 120 bpm and MAP below 100 mmHg to allow 
optimal counterpulsation and minimize alarms from the Driver. 
7. Commence over–night naso-gastric feeding post-operatively if diet not re–established at 
day 2 or if serum Albumin below 3.3 g/dL. 
8. Blood sugars: An Insulin infusion, titrated to Q1–4hr blood sugar measurement will be 
established in patients with diabetes or other glucose intolerance until a regular diet and 
normal diabetic therapy can be re–introduced. 
9. Active deep vein thrombosis management includes TED stockings, subcutaneous Clexane 
or similar and bed leg exercises. 
10. Early mobilization and graduated physiotherapy is to be conducted as tolerated from day 
1, but the driver should not be used in a wearable configuration in the first week or until 
the chest incision is stable and comfortable. Use of the driver with the vest should be 
gradually built up and used with assistance from physiotherapy or other hospital staff. 
11. The C–Pulse® can be de–activated intermittently for patients that are considered 
symptomatically stable per physician discretion (e.g. acceptable degree of shortness of 
breath and absence of dizziness), initially for short intervals (less than 5 minutes) once or 
twice a day, and this may be built up after 7–10 days post–operatively such that de- 
activation periods provide an opportunity for the patient to be free of the Driver for 15 
minute intervals during the day or night. The Driver should not be ‘Off’ for greater than 
30 minutes at any one time and not be ‘Off’ for a maximum of four hours total per day. 
For the extent of the trial, the device should be used at least 20 hours per day (i.e. 
device must be used greater than 80% of the time). 
12. Heart failure medications should be re–started cautiously and drug doses titrated to 
clinical effect. It is recommended that the following regime be used as a guideline for 
post–operative medications: 
• Dopamine or Dobutamine for first 1–7 days, weaned down 
• Diuretics at pre–op dose or higher (including IV infusion as required) from 
day 1: Diuretics may be weaned as indicated later in the post–operative 
period 
• ACE inhibitors from day 2–3 – aim to titrate to then maintain at pre-op 
dose for duration of the study follow-up 
• Beta blocker from day 5–7, as tolerated – aim to titrate to then maintain at 
pre-op dose for duration of the study follow-up 
13. Strict hygiene/hand washing must be practiced for all staff handling patient and lines. 
Remove all indwelling catheters as soon as possible. Change other lines regularly (at least 
every 4–7 days) as per hospital policy. 
14. The exit–site dressing should be changed as frequently as required post–operatively while 
ensuring that the percutaneous lead is immobilized – this may be up to 2–3 times per day 
in the first 1–2 weeks. If wounds are healing well and there is no discharge, then go to 
daily or second-daily dry dressings. Exit-site dressings must be limited to the least number 
of clinical personnel, and preferably done by the patient or care-giver as much as possible 

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after the early post-operative phase, to limit exposure to micro-organisms and to limit 
cross-contamination. 
15. Antibiotics IV peri-operatively as described above. Ongoing oral broad spectrum/gram 
negative cover is recommended for 10 days or until chest drains are removed and the exit– 
site has dried sufficient for once daily dressing only. 
16. Ongoing education to patient and care–givers on general hygiene e.g. regular hand 
washing and to treat percutaneous line gently and to avoid undue pulling, pushing or 
torsion. 
17. Maintain a routine dressing change and observe for signs of infection (refer to Appendix 
U for detailed infection control procedures): 
• Always wash hands and apply alcohol hand rub and use sterile gloves when 
handling the exit site. 
• Exit site should be examined and managed once per day (or more 
frequently if there is excessive moisture) by one person, specifically the 
wound should not be disturbed or inspected at any other time. 
• Irrigate wound site gently with Chlorhexidine solution and use sterile gauze 
to lift off any debris. Dry with clean sterile gauze. Keep the exit site dry 
between dressings. Use 2–3 small square gauzes or similar (e.g. Softwik), 
alternately split, to securely surround the percutaneous lead, and secure 
with tape or similar. 
• Wound deterioration is usually caused by excess moisture. Increase 
dressings per day until this resolves – also consider oral broad spectrum 
antibiotic or similar. 
• If wounds not responding to increased dressings, change wound irrigation 
solution (examples include 2% Chlorhexidine gluconate in normal saline, 
or Vancomycin in normal saline 2g/L) 
• Swabs for culture should only be taken of copious or purulent discharge. 
Blood cultures should be done if the patient is to be treated with antibiotics 
or if there is evidence of sepsis. 
18. Showering: If the patient is symptomatically stable while disconnected from the device, 
then the interface can be capped off, allowing the patient to shower. Leave the dressing 
intact during showering – cover the exit site and capped off connector with a 4x4 gauze 
sealed with an occlusive adhesive plastic dressing such as Tegaderm. It is recommended 
that the patient be sitting on a stool or chair initially to avoid the risk of vasodilation 
hypotension. The dressing should be changed, per above, following showering. 
19. Instruct patient to avoid sleeping on abdomen to avoid gas tube complications. 
20. Educate patient and care–giver on how to operate the drivers, per the Patient Handbook. 
Training of the patient and/or caregiver will be documented. 

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Hospital Discharge 
Preparation 
Educate patient and care–giver on how to operate the Driver. Provide the Patient with the 
C–Pulse® System Patient Manual and contact details for clinical personnel at the clinical 
site hospital. Refer to Appendix M for discharge checklist. 
Discharge Criteria 
Discharge should be based on the following criteria, which are based upon initial clinical 
experience in the ANZ pilot study. 
• Healing wounds, and with no signs of infection or sepsis 
• Oxygen saturation greater than or equal to age–predicted O2 saturation on room air 
• Sinus rhythm or atrial arrhythmia with ventricular rates < 120 bpm 
• Patient can walk 30 meters with the device without stopping due to shortness of 
breath/muscle fatigue/unsteady gait/pain 
• Caregiver or patient demonstrates aseptic technique in changing exit site dressing 
• Patient and caregiver independently demonstrate connection and disconnection of 
the Drivers, changing and recharging batteries, and to understand and respond to 
the Driver alerts and alarms 
• Home assessment visit prior to discharge may be completed to assess 
environmental conditions 
• All scheduled follow-up testing is completed 
The patient should not be discharged if any of the following issues are present: 
o Unresolved system malfunction 
o Back-up equipment is not available 
o Unresolved adverse event that threatens patient safety 
o Patient requires any treatment for disease, illness, mental or physical 
disability that cannot be provided outside the hospital 
Readmission 
Should the patient be re-hospitalized at any time post index hospitalization, the Unscheduled 
Follow-up Form should be completed. While hospitalized, the Follow-up Forms will continue to 
capture data and adverse events should be documented on the adverse event forms should they 
occur. When the patient is discharged again, the patient should be assessed per the discharge 
criteria to ensure they continue to meet the criteria. 

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Post-Implant Follow–up Testing and Data Collection 
Post–Implant Testing and Data Collection Summary 
The complete reference list of post–implant testing and data collection that will be 
performed at each time point is included in Table 3. 
Unscheduled Follow–up Visits 
If patients are seen between protocol–scheduled visits because of clinical symptoms 
requiring readmission, device reprogramming, etc. a follow–up form must be completed 
with all appropriate sections. In addition, all adverse events must be documented 
throughout the study. 
System Modifications 
Immediately contact Sunshine Heart clinical support team if a need is suspected for 
system modification (component or system replacement). In the event that the C-Pulse® 
System requires modification (e.g. Cuff or PIL) a System Modification Form should be 
completed along with an adverse event form. Modifications should be done only in 
communication with Sunshine Heart Service personnel, unless the modification is a 
medical emergency. In which case, Sunshine Heart personnel should be notified as soon as 
possible. In addition, the System Modification Form should be completed documenting 
the removal of the existing device or component. The C-Pulse® component(s) should be 
processed according to the Explant Handling Instructions and returned to Sunshine Heart 
or designee. 
In the event of a system modification, including component removal, reposition or 
replacement of the entire C-Pulse® system, the follow–up schedule for the patient will 
remain unchanged (i.e. the patient should continue to be seen for follow–up and associated 
forms should be completed based on the original follow–up schedule). All adverse events 
should be reported and classified by the investigator. Additionally the CEC will provide 
further classification of adverse events. 
Adverse Event Reporting 
Overview 
Information on adverse events (AE) will be collected throughout the study. Upon 
identification, the investigator completes the adverse event information via the Adverse 
Event eCRF. Sunshine Heart clinical personnel or designee may request further 
information from the investigator if necessary for review of the event with the Clinical 
Event Committee (CEC). 
The following information will be collected in the database: the date of event onset, 
seriousness of the event, the relationship of the event to the implant procedure, device, 
concomitant medications, patient management, other actions taken as a result of the event, 
and the outcome of the event. 

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Adverse Event Definitions 
Definitions are listed below for anticipated adverse events. The definitions are consistent 
with Version 2.2 adverse event definitions for the Intermacs® registry with the exception 
of Major Bleeding which does not have a minimum standard of transfusion. Aortic 
Disruption has been added in addition to the Intermacs® registry definitions as an 
additional screening for safety with respect to the C-Pulse unique application. 
Major Bleeding 
An episode of internal or external bleeding that results in death, the need for re-operation 
or hospitalization; or necessitates transfusion of red blood cells. 
NOTE: Hemorrhagic stroke is considered a neurological event and not as a separate 
bleeding event. 
Cardiac Arrhythmias 
Any documented arrhythmia that results in clinical compromise (e.g., oliguria, pre- 
syncope or syncope) that requires hospitalization or occurs during a hospital stay. Cardiac 
arrhythmias are classified as 1 of 2 types: 
1) Sustained ventricular arrhythmia requiring defibrillation or cardioversion. 
2) Sustained supraventricular arrhythmia requiring drug treatment or 
cardioversion. 
Pericardial Fluid Collection 
Accumulation of fluid or clot in the pericardial space that requires surgical intervention or 
percutaneous catheter drainage. This event will be subdivided into those with clinical 
signs of tamponade (e.g. increased central venous pressure and decreased cardiac output) 
and those without signs of tamponade. 
Aortic disruption 
Disruption to the intima of the ascending aorta. Disruption may be partial or complete (i.e. 
transmural), and the latter may result in contained or free rupture. Typically this would be 
documented initially by CT scan with contrast or by trans-esophageal echocardiography. 
Device Malfunction 
Device malfunction denotes a failure of one or more of the components of the MCSD 
system which either directly causes or could potentially induce a state of inadequate 
circulatory support (low cardiac output state) or death. The manufacturer must confirm 
device failure. A failure that was iatrogenic or recipient-induced will be classified as an 
Iatrogenic/Recipient-Induced Failure. 
Device failure should be classified according to which components fails as follows: 
1) Pump failure (implanted components of pump and any motor or other pump 
actuating mechanism that is housed with the implanted components). In the 
special situation of pump thrombosis, thrombus is documented to be present 
within the device or its conduits that result in or could potentially induce 
circulatory failure. 

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2) Non-pump failure (e.g., external pneumatic drive unit, electric power supply 
unit, batteries, controller, interconnect cable, compliance chamber). 
Hemolysis 
A plasma-free hemoglobin value that is greater than 40 mg/dl, in association with clinical 
signs associated with hemolysis (e.g., anemia, low hematocrit, hyperbilirubinemia) 
occurring after the first 72 hours post-implant. Hemolysis related to documented non- 
device-related causes (e.g. transfusion or drug) is excluded from this definition. 
Hepatic Dysfunction 
An increase in any two of the following hepatic laboratory values (total bilirubin, aspartate 
aminotransferase/AST and alanine aminotranferease/ALT) to a level greater than three 
times the upper limit of normal for the hospital, beyond 14 days post-implant  (or if 
hepatic dysfunction is the primary cause of death). 
Hypertension 
New onset blood pressure elevation greater than or equal to 140 mm Hg systolic or 90 
mm Hg diastolic (pulsatile pump) or 110 mm Hg mean pressure (rotary pump). 
Major Infection 
A clinical infection accompanied by pain, fever, drainage and/or leukocytosis that is 
treated by anti-microbial agents (non-prophylactic). A positive culture from the infected 
site or organ should be present unless strong clinical evidence indicates the need for 
treatment despite negative cultures. The general categories of infection are listed below: 
Localized Non-Device Infection 
Infection localized to any organ system or region (e.g. ) without evidence of 
systemic involvement (see sepsis definition), ascertained by standard clinical 
methods and either associated with evidence of bacterial, viral, fungal or protozoal 
infection, and/or requiring empirical treatment. 
Percutaneous Site and/or Pocket Infection 
A positive culture from the skin and/or tissue surrounding the drive line or from 
the tissue surrounding the external housing of a pump implanted within the body, 
coupled with the need to treat with antimicrobial therapy, when there is clinical 
evidence of infection such as pain, fever, drainage, or leukocytosis. 
Internal Pump Component, Inflow or Outflow Tract Infection 
Infection of the implanted C-Pulse Cuff documented by positive site culture. 
Sepsis 
Evidence of systemic involvement by infection, manifested by positive blood 
cultures and/or hypotension. 
Myocardial Infarction 
Two categories of myocardial infarction will be identified: 

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Peri-Operative Myocardial Infarction 
The clinical suspicion of myocardial infarction together with CK-MB or Troponin 
> 10 times the local hospital upper limits of normal, found within 7 days following 
implant together with ECG findings consistent with acute myocardial infarction. 
Non-Perioperative Myocardial Infarction 
The presence at > 7 days post-implant of two of the following three criteria: 
a) Chest pain which is characteristic of myocardial ischemia, 
b) ECG with a pattern or changes consistent with a myocardial infarction, 
and 
c) Troponin or CK (measured by standard clinical pathology/laboratory 
medicine methods) greater than the normal range for the local hospital 
with positive MB fraction (≥ 3% total CK). This should be accompanied 
by a new regional LV or RV wall motion abnormality on a myocardial 
imaging study. 
Neurological Dysfunction 
Any new, temporary or permanent, focal or global neurological deficit ascertained by a 
standard neurological examination (administered by a neurologist or other qualified 
physician and documented with appropriate diagnostic tests and consultation note). The 
examining physician will distinguish between a transient ischemic attack (TIA), which is 
fully reversible within 24 hours (and without evidence of infarction), and a stroke, which 
lasts longer than 24 hours (or less than 24 hours if there is evidence of infarction). The 
NIH Stroke Scale and Modified Rankin (for patients > 5 years old) must be re- 
administered at 30, 60 and 90 days following the event to document the presence and 
severity of neurological deficits. Each neurological event must be subcategorized as: 
1) Transient Ischemic Attack (acute event that resolves completely within 24 
hours with no evidence of infarction) 
2) Ischemic or Hemorrhagic Cardiovascular Accident/CVA (event that persists 
beyond 24 hours or less than 24 hours associated with infarction on an imaging 
study) 
Psychiatric Episode 
Disturbance in thinking, emotion or behavior that causes substantial impairment in 
functioning or marked subjective distress requiring intervention. Intervention is the 
addition of new psychiatric medication, hospitalization, or referral to a mental health 
professional for treatment. Suicide is included in this definition. 
Renal Dysfunction 
Two categories of renal dysfunction will be identified: 
Acute Renal Dysfunction 
Abnormal kidney function requiring dialysis (including hemofiltration) in patients 
who did not require this procedure prior to implant, or a rise in serum creatinine of 

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greater than 3 times baseline or greater than 5 mg/dL (in children, creatinine 
greater than 3 times upper limit of normal for age) sustained for over 48 hours. 
Chronic Renal Dysfunction 
An increase in serum creatinine of 2 mg/dl or greater above baseline, or 
requirement for hemodialysis sustained for at least 90 days. 
NOTE: Contrast-induced nephropathy must be evaluated within one week post-baseline 
CT scan. Patients with an increase in Creatinine ≥ 0.5 mg/dL or a greater than 20% 
reduction in GFR must be followed until resolution of the decrease in renal function. This 
will be tracked as an observation via the follow-up form and should not be reported as an 
adverse event. 
Respiratory Failure 
Impairment of respiratory function requiring reintubation, tracheostomy or (for patients 
older than age 5 years) the inability to discontinue ventilatory support within six days (144 
hours) post-implant. This excludes intubation for re-operation or temporary intubation for 
diagnostic or therapeutic procedures. 
Right Heart Failure 
Symptoms and signs of persistent right ventricular dysfunction [central venous pressure 
(CVP) > 18 mmHg with a cardiac index <2.0 L/min/m2 in the absence of elevated left 
atrial/pulmonary capillary wedge pressure (greater than 18 mmHg), tamponade, 
ventricular arrhythmias or pneumothorax] requiring RVAD implantation; or requiring 
inhaled nitric oxide or inotropic therapy for a duration of more than 1 week at any time 
after implantation. 
Arterial Non-CNS Thromboembolism 
An acute systemic arterial perfusion deficit in any non-cerebrovascular organ system due 
to thromboembolism confirmed by one or more of the following: 
1) standard clinical and laboratory testing 
2) operative findings 
3) autopsy findings 
This definition excludes neurological events. 
Venous Thromboembolism Event 
Evidence of venous thromboembolic event (e.g. deep vein thrombosis, pulmonary 
embolism) by standard clinical and laboratory testing. 
Wound Dehiscence 
Disruption of the apposed surfaces of a surgical incision, excluding infectious etiology, 
and requiring surgical repair. 
Other 
An event that causes clinically relevant changes in the patient’s health (e.g. cancer). 

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Adverse Event Classification 
All reported adverse events will be classified by the investigator, based on the following 
categories: 
• Relatedness (i.e. device, procedure, concomitant medication, or patient 
management); 
• Timing (i.e. pre–implant, implant or post–implant); 
• Serious events (i.e., result in death, are life-threatening, require surgical 
intervention, result in permanent disability, require hospitalization or 
hospitalization is unduly prolonged). 
• Status (i.e. ongoing or resolved) 
Device Related 
An adverse event will be considered device related if it is a direct result of, or is affected 
by the presence, or operation (intended or otherwise) of the investigational device. 
Procedure Related 
An adverse event will be considered procedure related if it is a direct result of the 
implantation procedure, which cannot be directly attributed to any particular device or 
implant tool. 
Patient Management Related 
An adverse event will be considered related to patient management if it is a direct result of 
the medical complexities of managing the co–morbidities of heart failure. 
Concomitant Medication Related 
An adverse event will be considered related to concomitant medication when it is 
reasonable to believe that the event is directly associated with medications used in 
conjunction with the investigational device and it is not otherwise specific to the device, 
procedure or patient management. 

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Unavoidable Events 
The events listed in Table 5 are considered minor and if the onset occurs within the 
timeframe specified, are not subject to adverse event reporting. 
Table 5. Unavoidable Events 
Event Description 
Timeframe 
(post–implant) 
Anesthesia related nausea/vomiting 
24 hours 
 
Low–grade fever (<102 degrees F) 
48 hours 
Minor incision/exit site pain 
72 hours 
 
Minor, localized tenderness, swelling, oozing, etc. at incision 
sites 
72 hours 
Early post–operative pain associated with endotracheal tube 
placement and mechanical ventilation 
72 hours 
Electrolyte imbalance without clinical sequelae 
72 hours 
Systolic and diastolic blood pressure changes that do not require 
treatment or intervention 
On–going 
Chest tube drainage or blood loss not requiring intervention and 
hematocrit remaining above 25% 
72 hours 
Sinus bradycardia and tachycardia that does not require 
intervention 
On–going 
Adverse Event Reporting to IRB and Regulatory Agencies for Unanticipated Device Events 
The investigator must report any unanticipated adverse device effects (UADE) to the 
Sponsor (Sunshine Heart) and IRB within 10 days after the investigator first learns of the 
event. The Sponsor must report any UADE to the regulatory agencies, IRBs, and all 
investigators within 10 days of receipt of notice of the event. 
An unanticipated adverse device effect is defined as: 
Any serious adverse effect on health or safety or any life-threatening problem or death 
caused by, or associated with, the device, if that effect, problem or death was not 
previously identified in nature, severity, or degree of incidence in the protocol or 
application (including a supplementary plan or application), or any other unanticipated 
serious problem associated with a device that related to the rights, safety, or welfare of 
subjects. [21 CRF 812.3 (s)] 
Patient Deaths 
All patient deaths must be documented on the Study Exit/Death Form. If the patient dies 
during the study, notify the Sunshine Heart field support personnel as soon as possible 
upon first learning of the death. Follow any IRB requirements for reporting of deaths or 
adverse events. 

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In the event of a patient death, efforts should be made to retrieve the implanted device and 
to obtain an autopsy in order to assess the state of the heart and aorta. A sample of the 
aorta beneath the C-Pulse® Cuff should be collected for analysis. Please call Sunshine 
Heart Clinical Support for more instruction. For patients who do not undergo autopsy, 
written documentation from the investigator will be required regarding circumstances as to 
why an autopsy was not performed. The device will be analyzed by local staff and 
Sunshine Heart clinical support personnel according to a standardized device retrieval 
protocol. 
A death summary and an autopsy report are required, please send upon completion to 
Sunshine Heart to provide to the adjudication committee. 
Explant Handling and Final Device Disposition 
Promptly call Sunshine Heart Clinical Support for instruction regarding Explant Handling. 
Cultures should be taken from the device implantation site along with visual analysis and 
photographs when possible. Explanted products should be returned to Sunshine Heart for 
analysis. 
Complete the Study Exit/Death Form. Report all associated adverse events. Update the 
Device & Equipment Disposition Log with all products. If the device is not returned to 
Sunshine Heart, justification must be provided in the log. 
Patient Withdrawal and Study Exit 
A Study Exit/Death Form shall be completed if patient is unable to or refuses to continue 
participation in the study. Notify the Sunshine Heart clinical support team as soon as 
possible upon learning of a patient withdrawal/study exit. 
If the patient fails to comply with follow–up visits, the study center must make repeated 
attempts to contact the patient. Each attempt to contact the patient must be documented in 
the patient’s records and on the Study Exit/Death form. 
If the patient officially withdraws from the study, the investigator will document the 
reason for withdrawal and indicate any relationship of the withdrawal to the study or the 
device on the Study Exit/Death form. 
If a patient withdraws from the study at any time, there will be no penalty or loss of future 
medical care. 

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STATISTICAL METHODS AND DATA ANALYSIS 
 
This feasibility study intends to examine the effect of C-Pulse® on long-term heart failure, and to 
look for trends in performance indicators. This study is not powered to detect statistical 
significance. As such, clinical judgment is required to assess device safety and potential efficacy 
from data collected during this study. This clinical judgment will be provided by the DSMB. 
Justification of Methodology 
This study is designed as an open-label single-arm study to develop a further understanding of 
the C-Pulse®. It will provide safety and efficacy information for patients in whom C-Pulse® is 
implanted and maintain counterpulsation for six months or longer. 
At six months post-procedure, the patients will provide an adverse event profile related to 
surgical placement of the C-Pulse® and six months employment of C-Pulse® counterpulsation. 
After six months of the study there will be additional information related to the adverse event 
profile. The patients will provide an adverse event profile for patients in whom C-Pulse® is 
placed and maintain counterpulsation for greater than six months. 
Similarly, these patients will provide an efficacy profile. At six months post-procedure, the 
patients will provide information on how well a patient improves since baseline through six 
months of counterpulsation. After six months these patients provide additional efficacy 
information related to how well a patient improves since baseline through greater than six 
months of counterpulsation. 
Primary Safety Measures 
The safety of the C- Pulse® will be evaluated by reviewing a composite of the device-related 
adverse events through six months, as classified by the CEC. The composite device-related 
adverse event rate will be the percent of patients who experience at least one of the following 
adverse events as adjudicated by the CEC as device-related out of the total number of patients: 
• Death 
• Neurological Dysfunction 
• Aortic Disruption 
• Myocardial Infarction 
• Major Infection 
• Any other device-related adverse event (as adjudicated by the CEC) 
The definitions for these adverse events are provided in the Adverse Event Definitions section. 
Performance Requirements 
Safety will be represented in the composite device-related adverse event rate which will be 
reported with its 95% two-sided exact confidence interval. The composite device-related 
adverse event rate will be assumed to follow the Binomial Distribution. The DSMB will 
decide the clinical acceptability of this observed event rate in assessing trial success. 
Additionally each event will be presented with its respective rate and confidence interval. 
Death will be separated into deaths that occur before 30-days post-procedure and those 
that occur between 30-days post-procedure and 6 months. 

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Efficacy measurements 
The efficacy of C-Pulse® will be evaluated by assessing the change of the efficacy 
variables from baseline to 6 months post-implant. The following measurements will be 
taken at baseline and 6-months. 
• 
Peak VO2 
• 
Quality of Life as measured by the Minnesota Living with Heart Failure (MLWHF) 
• 
HF Symptoms as measured by NYHA 
• 
Six Minute Hall Walk Test 
Performance Requirement 
Trial success will be evaluated by analyzing each patient’s response to the four efficacy 
variables. A responder analysis will for each patient will performed assessing the 
response to each of the four efficacy variables. Each efficacy variable will be assessed for 
clinical improvement (“responder”), decline (“non-responder”) or no change 
(“indeterminant”). 
Clinical improvement will be defined for each efficacy variable as: 
• 1.2 ml/kg/min improvement in peak VO2 
• 7 point improvement in MLWHF score 
• 1 class improvement in NYHA 
• 50 meter improvement in the Six Minute Hall Walk 
Clinical decline will be defined for each efficacy variable as: 
• 1.2 ml/kg/min decrease in peak VO2 
• 7 point decrease in MLWHF score 
• 1 class decrease in NYHA 
• 50 meter decrease in the Six Minute Hall Walk 
A patient that shows no improvement or decline in a particular endpoint will be labeled as 
“indeterminate” for that endpoint. 
The overall percentage of responders, non-responders and indeterminates for each efficacy 
variable along with the respective 95% two-sided exact confidence interval will be 
presented. Additionally the point estimate for the average change and its respective 
standard deviation will be presented for peak VO2, MLWHF, and the Six Minute Hall 
Walk. The improvement in NYHA will be presented by a cross-tabulation summary. The 
DSMB will decide the clinical acceptability of this responder analysis in assessing trial 
success. 

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Secondary Objectives 
The secondary objectives are descriptive in nature and will be evaluated in order to gain 
additional information regarding the C-Pulse® system. There are no specified 
performance criteria for these objectives. For continuous measures the mean, standard 
deviation, minimum and maximum values will be presented. For categorical variables the 
frequency and percent will be presented. 
Endpoints consistent with the primary safety and efficacy objectives will be evaluated at 
all additional time points. 
1. The adverse event rate will be presented at 3, 6, 12 and 18 months post- 
procedure, and annually for years 2-5 post-procedure. 
2. The change from baseline to follow-up will be evaluated for peak VO2, Six 
Minute Hall Walk, MLWHF, Fatigue Impact Scales and heart failure symptoms 
from NYHA. 
The device failure rate will be quantified. Failure will be defined as both failure of the 
device, and failure of the device to be programmed to the treatment. 
Additionally, the adverse event rate for each of the adverse events described in the Adverse 
Event Definitions section – pages 36-40 – will be provided. Exact 95% two-sided 
confidence intervals with an underlying Binomial Distribution will be provided for each 
event. Adverse events will also be tabulated by attribution (seriousness, device-relatedness, 
and procedure-relatedness) according to the CEC. 
The following additional efficacy measures will be analyzed at each time point to evaluate 
the efficacy of the C- Pulse® System. For these measures the averages and the average 
change from baseline to each follow-up period will be presented along with the trend over 
time: 
• Hemodynamic measures are from right heart catheterization (RHC): Cardiac 
Index (CI), Pulmonary Artery Pressure (PAP), Pulmonary Capillary Wedge 
Pressure (PCWP), and Cardiac Output (CO). 
• Quality of Life 
• 
Kansas City Questionnaire. 
• Blood tests (e.g. Serum sodium, serum creatinine, serum bilirubin, hemoglobin, 
ALT and AST). 
• Concomitant cardiovascular medications 
The following measures will also be summarized: 
• 
Re-hospitalization (HF-related and all-cause) 
• 
Duration of support/survival duration. 
• 
Length of time to ICU and hospital discharge 
• 
Device evaluation – Device log and C-Pulse® User log will be evaluated and 
summarized. Average daily device use will be provided for each time period. 

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Sample Size Determination 
This is a single-arm study designed to determine the safety of the C-Pulse® as well as give 
an insight into the efficacy of counterpulsation. 
Because estimates from this study will be used to power the pivotal study, this study must 
be able to provide such estimates. A sample size of 20 implanted patients is considered 
clinically sufficient to give indications of both safety and potential efficacy. With this 
sample size, we feel we can decide whether to proceed to a pivotal study, determine 
endpoints for such a study, and design the study to answer the proposed hypotheses. Up 
to approximately 10 additional subjects may be enrolled to account for subjects who do 
not meet inclusion/exclusion criteria involving non-standard clinical practices. 
Subjects for Analysis 
Patients will be included in two analyses. The primary analysis will be an “as- treated” 
analysis, wherein only subjects in whom the device is placed are analyzed. The secondary 
analysis will be an “intention to treat” analysis, wherein all followed-up subjects will be 
analyzed. 

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RISK ANALYSIS 
 
SHC has evaluated the potential risks and benefits (listed below) associated with the C-Pulse® 
and its appropriateness for therapy for symptomatic Stage C HF patients with NYHA Class III– 
ambulatory Class IV symptoms. Evaluation is based on the preclinical and clinical experiences 
to date. The adverse event definitions in the previous sections highlight and expose a standard 
level of expected risks. Any unanticipated risks and associated events will be captured through 
the adverse event reporting. 
Potential Risks 
Risks Related to the Implantation Procedure 
Surgical risks along with mitigations specific to the C-Pulse® system include: 
• Damage to Cuff on implantation not detected 
• Misplacement of ECG lead – not able to sense ‘R’ wave appropriately 
Implantation is an invasive procedure requiring a median sternotomy and the use of 
general anesthesia and mechanical respiratory support. The potential risks associated with 
the implant procedure also include those associated with any cardiothoracic surgery, 
including implantation of devices and include the following: 
• Bleeding 
• Infection 
• Neurological Dysfunction 
• Renal Dysfunction 
• Cardiac Arrhythmias 
• Pericardial Fluid Collection 
• Aortic disruption 
• Device Malfunction 
• Hemolysis 
• Hepatic Dysfunction 
• Hypertension 
• Myocardial Infarction 
• Psychiatric Episode 
• Respiratory Failure 
• Right Heart Failure 
• Arterial Non–CNS Thromboembolism 
• Wound Dehiscence 
• Death 
There may be other unforeseen risks. 

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Risk Related to the Investigational Device 
The C-Pulse ICP is designed to allow implantation with a satisfactorily low hospital 
mortality risk and to allow intermittent use to augment native cardiac function as well as 
to improve the quality of life in patients in Stage C, Class III/IV heart failure. Avoiding or 
minimizing surgical risk factors such as blood contact, anti-coagulation, bleeding, 
thromboembolism, prolonged operating time, and device-dependent circulation are 
important when considering the design of C-Pulse®, the operative mortality risk associated 
with implanting the device and the potential for long-term benefit to a patient’s quality of 
life and heart function. C-Pulse® has undergone extensive component and system testing. 
Potential failure modes that Sunshine Heart was not able to mitigate through testing have 
undergone individual risk analysis. Key risks associated with the device and how they 
have been minimized or mitigated are detailed as follows. 
Lack of effect – insufficient relief from heart failure symptoms 
Given the natural toroidal shape of the ascending aorta, the greatest opportunity for 
displacement of blood from the ascending aorta with the least amount of aortic wall strain 
is for inward displacement of the outer curvature of the ascending aorta – a so-called 
“thumb-printing” action that results in a rolling back and forth of the outer aortic wall. 
The C-Pulse Cuff actuator is positioned on the outer curvature of the aorta, pre-shaped like 
a cap when deflated – the inflation/deflation port is positioned radially in the central 
aspect of the outer part of the balloon. A circumferential Dacron wrap holds the actuator 
in place. As the actuator inflates, the outer ascending aortic wall is pushed toward the 
posterior inner arc of the ascending aorta.  The wrap stays circumferential, and the 
actuator takes on a ‘lens’ shape as it fills, and displaces blood in the ascending aorta. The 
ascending aorta provides for a relatively large volume of blood displacement, which is key 
to effective counterpulsation. 
Counterpulsation is proven to be more effective the closer this occurs to the aortic 
valve.18,19,20 The pre-systolic unloading action at the level of the ascending aorta is more 
direct on the left ventricle. In the descending aorta, there are diffusive losses, with 
multiple branches, bi-directional blood volume displacement, and less precision of timing 
to aortic valve opening and closing. Diastolic counterpulsation on the ascending aorta, 
against the closed aortic valve, may also contribute more directly to forward cardiac 
output by creating unidirectional flow. 
The C-Pulse Cuff has a maximum target volume setting of 20–30cc, dependent on Cuff 
size. The degree of efficiency of counterpulsation on the ascending aorta is of the order of 
2–3 times compared to the descending aorta. As such, a displacement volume in the 
ascending aorta of 16–20 ml might be comparable to a 40 ml descending thoracic aortic 
IAB. Although not proven by FDA, aortomyoplasty displacement volume may be as little 
as 15 ml, and counterpulsation is run at 1:2 and has good clinical effect. In addition, the 
Kantrowitz counterpulsation device is positioned in the descending aorta and has a 
 
 
18 [Furman 1970] 
19 [Gitter 1998] 
20 [Davies 2002] 

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maximum capacity of 60 ml but operates clinically at a maximum of 50–55 ml at 1:1 
counterpulsation, with good clinical effect. 
The dimensions of the ascending aorta were determined by literature review, and by 
cadaveric, intra-operative, and radiology studies. The cuff dimensions were based on 
these measurements; to allow a certain inflation profile that would fit most aortas, but if 
over-inflated would not allow the intimal surfaces to touch, and to at least match an 
equivalent counterpulsation volume to those achieved in humans with predicate devices 
with clinically significant results.21 The C-Pulse Cuff is thus supplied in three sizes 
designed to fit to a range of aortic dimensions and to minimize absolute strains and rates 
of change of strains in the Cuff and aorta during inflation and deflation, whilst allowing 
significant blood volume displacement in the aorta. 
The ascending aorta was selected over the descending thoracic aorta because of: 
• surgical access 
• counterpulsation on ascending aorta is unidirectional and more efficient 
• ascending aortic diameter is greater than the descending thoracic therefore less 
wall movement is required for a given volume displacement 
• no side branches such as intercostal and spinal arteries 
• uniform ascending aortic anatomy 
• low incidence of atheromatous disease in the ascending aorta 
The wrap design allows for minimal axisymetric expansion of the aorta during systole yet 
containment of the actuator ensures the proper inward inflation profile for effective 
diastolic counterpulsation. 
R wave detection by the Driver is highly specific and sensitive to ensure the Driver is able 
to deflate the balloon effectively in relation to the onset of systole and to not remain 
inflated during any systolic event, including from ventricular premature beats, paced beats 
or other arrhythmias. The gas line is designed for high air flow rates, thus ensuring rapid 
balloon inflation and deflation. These features are key in ensuring the C-Pulse system is 
able to effectively counterpulsate. 
If the left ventricular failure is severe, counterpulsation may not prove adequate to support 
the patient in the short or long term. The device is not intended to fully support the 
systemic circulation. The C-Pulse is not indicated in Class IVb heart failure patients; 
those that are not ambulatory, are inotrope dependent or have severe multi–organ failure. 
Improving left heart function may reduce the load on the right heart, however if the right 
heart failure is severe, or is secondary to primary pulmonary hypertension, then there 
exists a risk that C-Pulse counterpulsation will not be as effective. 
 
 
 
 
 
21 [Legget 2005] 

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Device Failure 
The pre-shaped extra-aortic non-blood contacting design of the Cuff significantly reduces 
any consequence of device failure. 
The Cuff actuator has been designed for maximal durability by designing to minimize 
strain in the flexing membrane. Finite element analysis (FEA) of the current design was 
iterated using ABAQUS FEA software to reduce the strain to an acceptable level. The 
greatest area of strain is around the moving membrane. Key elements of strain related to 
the thickness of the membrane and to its edge radius. Varying aortic wall thickness 
between 1.5 – 2 mm had no significant effect. Membrane material thickness and the edge 
radius are most critical in minimizing strain in the C-Pulse Cuff. 
The membrane edge radius gets compressed to less than its molded edge radius when 
assembled on the aorta and assumes the wall tension of the pressurized aorta. It does not 
crease. The rolling edge design has the further advantage of allowing the Cuff better 
conformation to the slight variations in individual aortic dimensions. 
The Cuff needs to comply to the natural shape of the ascending aorta to not cause local 
pressure. The wrap is designed to maintain the actuator in position on the aorta, and to 
ensure it deflects inward. A pre-shaped wrap made of woven Dacron, and with some 
strain relief feature in the top and bottom edges of the cuff to better transition from the 
cuffed aorta to the non-cuffed aorta has been used. Woven Dacron has proven long-term 
use clinically as both a peri-vascular wrap and as a graft replacement, and has only 5% 
stretch long-term in vivo. It is secured to itself using standard suturing. 
The inflation fluid is filtered room air. Accelerated over-pressure device testing indicates 
that the balloon is very unlikely to fail within the first four years of continuous use. 
Premature failure may occur if the inflation membrane of the Cuff migrates under the 
wrap and causes a crease line and counterpulsation is continued. The expected 
consequences of a persistent leaking balloon may include surgical emphysema or 
pneumothorax. Leakage of non–sterile air may also predispose to mediastinal infection. 
There is negligible risk of air embolism if the aorta is not compromised. 
There is a risk of a needle puncture hole being made intra-operatively. Surgeons are 
required to undergo multiple implantations of the cuff on a mock inflated ascending aorta 
prior to their first implantation, and there is an intra-operative check-list to reduce the 
chance of making an inadvertent needle-hole, and to check for and discover any such hole 
and thus replace the cuff. 
The Driver is designed to detect air leaks and trigger an alarm and to stop. The Driver is 
designed to detect air leaks and will immediately alarm and stop if a major leak occurs. 
The electronic system is also used to detect impending malfunctions by performing 
diagnostic tests on the system. Safety features built into the Driver are designed to protect 
the patient in the event of system failure, as well as to protect the integrity of the system. 
Safety features include protection against current leakage, defibrillating voltages, failure 
of the microprocessor and power supply and over-inflation of the Cuff. 

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Device stoppage for any reason is not immediately dangerous to the patient, but the 
symptoms of heart failure may return. The device is engineered to resume a deflated state 
if there is a power loss or malfunction, thus the natural blood pathways of the heart and 
vasculature are preserved. 
Emboli arising from ascending aorta and risk of neurological damage 
The device does not contact blood thus in normal use there is no foreign surfaces in 
contact with the blood. Thromboembolism may result from ascending aortic disease or 
left ventricular mural thrombus. There is a risk such emboli may cause cerebral ischemia. 
If there is a breach of the intimal lining caused by the cuff then mural thrombus may 
develop and embolize. 
Significant contraindications for implanting the C-Pulse include pre-existing ascending 
aortic atheroma, particularly intimal thickening greater than 3mm or any mural thrombus 
or mobile atheroma or calcific or aneurysmal disease of the ascending aorta. Patient 
eligibility in this regard may be determined accurately by CT scan and/or 
echocardiography: CT specificity (as compared to epi-aortic scanning at surgery) has been 
reported at 98%. 22 
The incidence of atherosclerosis increases with age, the presence of coronary artery 
disease, and distance from the aortic valve. The ascending aorta is one of the areas least 
affected by atherosclerosis because there are no branches to create turbulence and the flow 
is vortical in nature given the natural shape of the ascending aorta.23 
In the pilot intra-operative clinical study to confirm safety and performance of a gas- 
driven C-Pulse Cuff in patients with normal ventricles undergoing OPCAB24, the Cuff fit 
all patients and counterpulsation was effective with approximately 50–70% compression 
of the aortic lumen. No patient that consented for the study was later excluded for aortic 
disease, and no complications arose. The right common carotid artery was monitored over 
20 minutes intervals with the device both on and off – there was no significant difference 
in the rate of high intensity transient signals (HITS) detected and there were no post- 
operative neurological events. 
The frequency of HITS has been studied in relation to various types of prosthetic aortic 
heart valves and LVADs. Most studies have measured HITS in the middle cerebral artery. 
Mechanical valves appear to have higher HITS rates25, but most appear to be harmless 
epiphenomena26. Thrombo-embolic events are prevalent in LVAD patients, and there may 
be a significant relationship between HITS and thrombo-embolic events; this may be 
 
 
 
 
 
 
22 [Davila–Roman 1999] 
23 [Leuprecht 2002] 
24 [Leggett 2005] 
25 [Laas 2003] 
26 [Nadareishvili 2002] 

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influenced in part by increased hemostatic activity despite aggressive anticoagulant 
therapy and in part by the type of LVAD in situ.27,28,29 
Aortic Rupture 
There are several examples of extra-aortic banding or counterpulsating, using different 
materials, and in different species. In humans, Dacron wraps have been used to support 
primary ascending aortic aneurysm repair as described in a number of clinical series, with 
10 year follow-up.30,31,32 Note that patients requiring an aorto-coronary graft had it placed 
via a hole cut in the Dacron wrap. There has been no reported instance of aortic dilation 
above or below the wrap. However, a poorly fitted or not well secured wrap may migrate 
and this may cause aortic erosion and subsequent false aneurysm formation.33 
The pre-shaped C-Pulse Cuff is designed to minimize the risk of migration – it is 
anatomically designed to conformally fit the toroidal ascending aorta between the 
sinotubular junction and the brachiocephalic artery. The Cuff cannot fully occlude the 
aorta, thus there is negligible risk of any abrasion of aortic wall surfaces. 
An infected Cuff may cause aortitis. If the infection is aggressive or left untreated, 
subsequent erosion of the aortic wall resulting in contained or free aortic rupture may 
result (see below). 
Device–related Infection – Intra-thoracic and Exit-site 
There exists the risk of mediastinal infection involving the implanted Cuff. This may 
occur as a result of inoculation at the time of implantation, or arise at long–term follow– 
up; the latter may be due to seeding of circulating microbes or from infection ascending 
from the exit–site. 
Perforation of the Cuff at the time of surgery is of concern as the air used to inflate the 
cuff is filtered but not sterile. There is no risk of air-leak and thus no risk of infection if 
the Cuff is not damaged. Cuffs are 100% checked during the assembly process and 
following complete assembly to confirm integrity. Bench testing of the Cuffs has 
demonstrated very high confidence of reliability beyond 6 years of cycling at significantly 
higher pressures than required clinically. However, there remains the risk that a leak could 
be made at the time of implant and this may potentially cause mediastinal infection. Thus 
diligence is required to ensure a needle-hole is not made at the time of surgery and if it is, 
that it be recognized and the cuff replaced prior to closing the chest. To this end, the 
methodology to implant the Cuff has been revised to allow visualization of the balloon at 
all times when placing sutures into the wrap, and intra-operative testing is a mandatory 
 
 
27 [Nabavi 2003] 
28 [Kofidis 2002] 
29 [Wilhelm 1999] 
30 [Barnett MG 1995] 
31 [Carel 1991] 
32 [Rubiscsek 1994] 
33 [Bauer 2003] 

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part of the procedure. Furthermore, bench and in vivo models have been developed to 
provide surgeon training prior to implantation. 
Infection of the cuff may lead to erosion of the aorta, with subsequent risk of septic 
thromboemboli and poses a significant problem. Early recognition of an infected Cuff and 
aggressive treatment will likely limit potential complications. Chest pain and/or fever of 
unknown origin should be thoroughly investigated. Removal of the Cuff is an option, 
which allows also surgical debridement and drainage as well as long-term antibiotic 
therapy. Other methods of cardiac support may be required in the interim. 
Infection risk may be reduced by careful selection of patients: excluding non-ambulatory 
patients or those in hospital on intravenous ionotropic support, those who are severely 
cachetic or have severe chronic renal failure may improve early healing post-surgery and 
reduce the risk of early device infection. Similarly, optimal implant techniques, 
appropriate use of antibiotics and avoiding nosocomial infections in indwelling catheters 
peri-operatively will minimize implant infection rates. The protocol is specific to 
reducing the risk of peri-operative infection. 
The presence of a percutaneous line creates a risk of long-term infection at the exit-site 
and specific guidelines are given to care-givers and patients for managing this wound site 
long-term. The percutaneous lead has been specifically designed to reduce the risk of 
infection – the outside diameter is approximately 5 mm, the material is Silicone, and the 
tubing is soft and flexible. Flockings exist subcutaneously to anchor the Lead in a manner 
similar to Tenkhoff and Hickman catheters.34 There is no device ‘pocket’ created. 
The Cuff and ECG lead can be terminated subcutaneously and sealed if the Percutaneous 
Lead is chronically infected or otherwise damaged and needs removal. 
Risks Related to the Study Conduct 
The methods for data collection involve only standard, well-established methods and do 
not differ from normal mechanical circulatory support device implantation and heart 
failure management follow-up practice. Therefore, the clinical study requirements of C– 
Pulse® pose no additional risk to the patient. 
Risk Minimization 
Sunshine Heart has attempted to minimize the risk of implanting the C-Pulse® through 
careful design and pre-clinical testing. Preclinical testing includes bench and animal 
testing to verify performance, software validation testing, destructive analysis and shock 
tests, and packaging qualifications. 
Risks normally associated with cardiac devices and their implantation will be minimized 
by selecting investigators who are experienced in the diagnosis and treatment of patients 
with end-stage heart failure. In addition, investigators will be trained on the device 
operation and protocol prior to participating in the study. Product labeling is also 
provided which further addresses risk mitigation. 
 
 
 
 
34 [Ash 1990] 

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Prior to implant patients should go through a complete cardiac evaluation. After 
implantation, patients will be followed at regular intervals to confirm that the device 
parameters are appropriate and to monitor the status of the C-Pulse® system. Frequent 
follow-up will promote faster identification and resolution of adverse events. The severity 
of system related events will be minimized by restricting use of the C-Pulse® to hospitals 
equipped with redundant systems and staffed by qualified, trained personnel. 
C-Pulse® Potential Benefits 
Anticipated benefits of the C-Pulse® may include: 
• Relief of symptoms 
• Improved QOL 
• Enhanced mobility 
• Home discharge 
• Freedom to disconnect from the external driver for short periods of time before 
noticing return of symptoms, particularly shortness of breath 
• Anti–coagulants not required 
• Increased diastolic coronary artery blood flow 
• Reduced systolic pulmonary artery pressures and mitral regurgitation 
• Increased cardiac index 
• Straightforward implant surgery 
• No cardio–pulmonary bypass 
• Avoid risk of lung and right heart complications associated with cardiopulmonary 
bypass – critical in patients with HF 
• Preserved pericardial sac around ventricles 
• Modular design 
• Implanted device is very small 
• There is no ‘pocket’ created 
• Device can be removed and infection treated if necessary 
• Subcutaneous line is long, and multiple flocking anchors are provided 
• Line exiting skin is made of biostable and biocompatible materials, is soft and 
flexible, and can be removed and/or replaced 
Overall advancement of medical and scientific knowledge that may benefit future patients 
may also be realized from this study. 
There may also be other benefits that are unforeseen at this time. 

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Justification for the Investigation 
The ethical conduct of a clinical trial of a new therapy relies on the promise the therapy 
has some benefit, but its efficacy to achieve this benefit is unknown and the new therapy 
always carries some risk (clinical equipoise) .35  A careful and complete presentation of 
the scientific merit for the trial, including evidence both for and against the investigational 
treatment, forms the ethical basis for the study design and conduct. 
Clinical Need 
There are over 1.4M people in the USA in Class III and IV heart failure. Biventricular 
pacemakers are indicated in patients with a wide QRS – approximately 30% of this 
population. Approximately 2200 heart transplants are done per year. A similar number 
might receive an LVAD as either a bridge to transplant or as destination therapy. 
There remain a very large number of people that may benefit from an improvement in 
their clinical status from NYHA Class III/IV to Class I/II. The targeted Patient population 
is defined by the expected natural history of heart failure. Figure 2Figure 2 highlights the 
trend of heart failure, and the relationship of severity of heart failure with repeat 
hospitalization and with mortality. 
Figure 2. Annual survival rate and frequency of hospitalizations versus NYHA 
Classification 
It can be seen from the figure that repeat hospitalizations, on a logarithmic scale on the 
right hand side, changes at a much greater rate compared to the mortality curve, with any 
change in the NYHA Class. In the patient group indicated for C-Pulse® i.e. NYHA Class 
III–IV, patients are characterized as beginning to have more frequent admissions to 
hospital or increasing length of stays, with significant cost burden, but remain ambulatory. 
Patients in late Class IV have a more rapidly escalating mortality rate, and are generally 
not ambulatory at all. 
 
 
 
 
 
35 [Warner–Stevens] 

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As the severity of disease increases, there is greater certainty regarding imminent death, 
and less certainty is required regarding the device performance and patient outcome after 
implantation. However, generally, increasing disease severity also increases the risk of 
adverse outcomes attributable more to the patient than the device. At lesser grades of 
severity, when death is not imminent, details regarding the expected function and quality 
of life with mechanical circulatory support become more critical. Patient preference for 
quality of life versus survival shows remarkable variation at every level of disease 
severity. 
From a practical standpoint, apart from those with high predicted in-hospital mortality (i.e. 
Cardiogenic Shock or Class IV with risk factors such as multi-organ failure) many patients 
exhibit a dynamic state that fluctuates over months, with exacerbations related to dietary 
indiscretion, seasonal viral infections, and other exogenous factors. 
Ambulatory heart failure patients on oral therapy are generally not as sick, but experience 
discomfort during any physical activity and may have discomfort while at rest. The 
hypothesis is that a mechanical circulatory support device will provide such patients with 
an improved physiologic and functional quality of life. The probability of survival at a 
specific time is not well established. End-points of interest include quality of life, all– 
cause and cardiac-related mortality, and morbidity, whereby a sustained improvement in 
quality of life and significantly less morbidity may be considered a significant benefit 
even if survival is equivalent. For ambulatory heart failure patients, a large component of 
the decision to receive investigational therapy is the degree to which the current clinical 
status is unacceptable. 
The objective of the C-Pulse® system is to provide an effective, low risk and low cost 
mechanical heart assist device for use in patients in NHYA Class III–IV. Basic safety has 
been demonstrated on a very sick group of patients (NYHA Class III–IV) in a Pilot Study 
in Australia and New Zealand. Significantly, there was no surgical-related mortality and 
while there were very good indicators for device performance in relation to heart failure 
symptoms and cardiac function, there was an incidence of early infection. The method of 
training, the Cuff itself, the percutaneous line, and the inclusion and exclusion criteria 
have all been modified to reduce this infection risk. Furthermore, the need for a back-up 
ECG sense lead in a subcutaneous pocket has been eliminated. 
The focus of the IDE Feasibility Clinical Investigation will be on safety but also on 
examining the dose–effect of counterpulsation, much like a Phase II drug trial. 
Measurements including Peak VO2, Quality of Life scores, LV function and blood tests 
will be made to allow planning for a pivotal study design. Assessment will be made of all 
adverse events. 
Study Design – Control Groups 
The IDE Study will be conducted in two phases: Feasibility is an open-label, single arm 
study to determine the safety of the device as well as examine the effect of different levels 
of counterpulsation. For the Pivotal trial, an expanded randomized double-blind crossover 
study is anticipated. 

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The template of the double-blind, randomized control trial has emerged as the gold 
standard for evaluating new pharmacological therapies. Multiple large, randomized, 
placebo-controlled trials established angiotension-converting enzyme inhibitors as the 
cornerstone of therapy36, and more lately beta-adrenergic blocking agents have shown 
longer-term improved hemodynamics and survival in recent large trials of mild-moderate 
heart failure37. Chronic use of intravenous inotropic drugs has not provided sustained 
hemodynamic improvements and mortality is increased. End points of survival, clinical 
status, cardiovascular function and cost-effectiveness can be evaluated using this template 
without either physician or patient knowing who has received the new therapy being 
tested. 
The inability to provide comparable placebo therapy (e.g. sham operations), strong patient 
preferences regarding invasive procedures, and the front-loaded risk of LVAD studies 
have complicated the evaluation of new mechanical circulatory support devices for 
advanced heart failure using a randomized control trial template. The impact of the device 
is more transparent than that of a drug, in part because the most obvious risks are front- 
loaded compared with those from new drugs. The combination of debilitating disease and 
unblinded therapy raises ethical issues – patients consenting to new trials are likely to be 
already biased toward the procedure and thus may perceive randomization to the control 
arm as a loss of hope, with potentially deleterious impacts on individual outcomes.38 
Furthermore, patient preference for specific therapies perceived to be life–saving may 
limit enrollment into the randomization process. 
Resynchronization therapy has, because of the nature of the device, allowed use of a 
randomized, double-blinded trial structure to evaluate its safety and efficacy. The device 
requires surgery for implantation, thus exposing front–loaded risk to all patients, but it can 
be tuned to optimize bi-ventricular timing or used in a simple pacing mode. 
C-Pulse acts to a) increase coronary blood flow, b) reduce ventricular afterload to reduce 
the workload of the left ventricle, and c) increase cardiac output. C-Pulse® offers the 
unique situation whereby the level of counterpulsation can be adjusted without the patient 
being cognizant of how much benefit he/she is receiving from the device. Cohen et al 
showed in a limited study of 20 patients a significantly higher velocity time integral across 
the LV outflow tract resulted when counterpulsated at 1:1 versus at 1:8. They did not 
show any difference with varying the balloon volume from 40 to 32 cc.39 
 
 
 
 
 
 
 
 
 
 
36 [Davis 1979] 
37  [Packer 2001] 
38  [Neaton 2007] 
39 [Cohen 1995] 

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Trial End–Points 
The End Points for a Clinical Trial are chosen according to the severity of disease in the 
population selected. The target population for this trial has been defined widely to include 
patients with the best natural history compatible with the degree of certainty that the 
device will provide an improvement. This will help maximize the generalization of the 
results. The primary endpoint should be clinically relevant and sensitive to the 
hypothesized effect of the treatment. End-points should be obtainable in all patients and 
be inexpensive to measure. Endpoints may include clinical outcomes such as death or 
morbid events such as repeat hospitalizations, or measures of quality of life such as 
NYHA Class or QOL scores. Surrogate measures of heart failure for heart assist devices 
have not been established but may strengthen a trial by showing correlation with clinically 
relevant findings. Composite endpoints may include clinical outcomes and surrogates, but 
should avoid combining safety and efficacy outcomes; composite structure has the 
advantage of reducing sample size, though selection of composites requires that the 
treatment has similar affect for all endpoints selected. 
The C-Pulse® is targeted at Class III–IV patients, where mortality is difficult to predict, 
but the quality of life of patients is poor enough to consider the need for an implantable 
heart assist device. The primary endpoint in this Feasibility study is safety, and will be 
assessed by showing the device is not associated with an unacceptable mortality or 
morbidity profile in the selected patient population, as judged by the DSMB. Performance 
variables will allow statistical planning of the Pivotal study and selection of appropriate 
endpoints and study design. 
Studies regarding NYHA Class III and IV patients also are useful to identify boundaries of 
expected changes in endpoints. 
Summary 
The objective of the feasibility clinical investigation shall be related to establishing or 
verifying the safety, and identify trends of efficacy and performance of the device, when 
used for its intended purpose and according to the documented instructions. The study 
may be expanded to a pivotal randomized double-blinded trial after taking into account the 
serious adverse event profile and anticipated levels of performance and efficacy as 
compared to other circulatory support devices. 
The primary objective of the feasibility study is to demonstrate reasonable safety in 
patients in Class III–IV heart failure. Placing C-Pulse® in suitable patients in ACC/AHA 
Stage C; NYHA Class III–IV HF with the objective of improving the patient’s quality of 
life and cardiac performance is justifiable based on the results of testing of the C-Pulse® 
device to date, and on the efficacy of clinical performance and safety data of similar 
devices, such as biventricular pacemakers, other forms of chronic counterpulsation, and 
LVADs. 

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STUDY OVERSIGHT AND INTEGRITY 
 
DESIGNATION OF SPONSOR, DATA MANAGER, AND AUDITOR 
 
 
 
Role 
Organization 
Address 
Contact Numbers 
 
 
Sponsor 
Sunshine Heart, Inc. 12988 Valley View Rd 
Eden Prairie 
Minnesota 55344 
Primary Contact: 
Aleela Baune 
 
952.345.4200 
 
 

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MONITORING PROCEDURES 
 
The Sunshine Heart C-Pulse™ study will be monitored according to the guideline 
summarized below. 
 
SUMMARY OF MONITORING PROCEDURES AND RESPONSIBILITIES 
 
 
It is the responsibility of the study sponsor (Sunshine Heart Inc.) to ensure that proper 
monitoring of the investigation is conducted and that IRB review and approval of the 
investigation is obtained. Monitoring visits will occur based on implant volume at the 
center or at least annually. Adequately trained Sunshine Heart or delegates appointed by 
the study sponsor will do study monitoring in order to ensure that the investigation is 
conducted, recorded and reported in accordance with: 
• The signed Investigator Agreement 
• The Investigational Plan 
• Applicable laws and regulations. 
Monitoring will be planned at the study site to assure compliance with the study protocol. 
The sponsor (or appropriate designee) must therefore be allowed access to the patients’ 
files as per the informed consent at the investigator’s site when so requested. 
 
INTERIM MONITORING VISITS 
 
 
Routine monitoring visits are made periodically to assess the Investigator’s adherence to 
the Investigational Plan, IRB review of the progress (if appropriate), maintenance of the 
records and reports and selection review of source documents for accuracy, completeness, 
legibility and omissions. The following factors will be taken into account when 
determining the frequency of the monitoring visits: patient accrual at each center, total 
number of patient enrolled at each center, and protocol compliance at each center. Each 
participating institution will be monitored once per year, at a minimum. 
The monitors will acquire information to assess the progress of the study (toward meeting 
study objectives) and identify any concerns that stem from observation of device 
performance and/or review of the investigator’s patient records, study management 
documents, device tracking and Patient Informed Consent documents. Resolution of 
concerns and completion of assigned tasks may be documented by the monitors. Source 
data verification and review of any ongoing finding may occur during monitoring visits. 

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STUDY CLOSURE 
 
 
Study closure is defined as a specific date that is determined when Sunshine Heart 
regulatory requirements have been satisfied per the Investigational Plan (IP) and/or by a 
decision of the business leaders for Sunshine Heart. Study closure visits will be conducted 
at all clinical sites in order to review record retention requirements, device disposition 
requirements, etc. with site personnel. A telephone contact may take the place of a study 
closure visit if appropriate (e.g. low patient enrollment, recent monitoring visit, etc.) 
 
NAME AND ADDRESS OF STUDY MONITORS 
 
 
Sunshine Heart will monitor investigational sites to ensure that the study is conducted, 
recorded and reported in accordance with the protocol, standard operating procedures 
(SOPs) and applicable regulatory requirements. 
Monitoring visits will be conducted by trained Sunshine Heart or designated 
representatives. A Monitoring Plan will be completed for the study and will identify the 
frequency of monitoring and further identifies the names of monitors. 
 
STUDY SAFETY 
 
 
Clinical Events Committee (CEC) 
A CEC will be established by Sunshine Heart or designee to assess, review, and classify 
all adverse events and deaths during the clinical study. Classification will include device- 
relatedness, seriousness, and procedure-relatedness. The committee will consist of a 
minimum of three physicians including a chairperson appointed by Sunshine Heart or the 
CEC committee. The CEC will regularly review and adjudicate reported adverse events 
including deaths. 
At the onset of the study, the CEC, along with support from Sunshine Heart will establish 
a charter outlining the minimum data required and the algorithm followed in order to 
classify an event. This charter will be approved by the committee during the first round of 
meetings. Members will be provided data summaries from the clinical study in a blinded 
fashion without site, patient or physician identification. 
Data and Safety and Monitoring Board (DSMB) 
A DSMB will convene, composed of a least one heart failure cardiologist, cardiac 
surgeon, medical doctor of associated disciplines and a biostatistician who are not directly 
involved in the trial. The DSMB will review the study data after enrollment of the first 
five patients. Enrollment of further patients will occur as the DSMB reviews the data. 
The DSMB will provide a report following the review and may recommend to Sunshine 
Heart to continue, modify or stop the trial based on their findings. The DSMB will 
provide further evaluation at least twice per year and after the first five patients are 
enrolled. If slow enrollment is experienced, the DSMB may meet less frequently. 

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Based on the data, the DSMB may recommend to Sunshine Heart to modify or stop the 
trial. All final decisions, however, regarding the trial modifications, rest with Sunshine 
Heart and the Medical Advisory Board. 

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TRAINING PROCEDURES 
 
Site training is required at all investigational sites. Each study site will be trained on all aspects of 
the protocol, device implantation and operation, as well as patient training in preparation for 
discharge. At the end of the training course, all participants should be competent in ensuring 
optimum care of the patient. In addition, each site will have identified a local expert user to 
provide continuing training to team members. 
The training program will be conducted according the Sunshine Heart standard operating 
procedures and quality system requirements. A summary of the contents and audience are 
included in the table below. 
 
 
Training component 
Audience 
Format required 
Surgical training 
• 
Surgeon 
• 
Cuff mock implant training 
• 
Observe Surgery, if possible 
• 
Mentor support at implant 
Expert users training 
• 
Cardiologists 
• 
Clinical coordinator 
• 
Surgeon 
• 
Product overview 
• 
Protocol overview 
• 
System/Programmer training 
Site Initiation /protocol 
training 
• 
All investigators 
• 
Study coordinator 
• 
Back-up study coordinator must be 
trained on protocol, ICH/GCP and 
investigator responsibilities 
• 
Self directed review of 
presentation by ALL 
Investigators and self assessment 
with optional independent 
education by Clinical trial staff 
AND 
• 
Meeting with key 
investigators/personnel & 
clinical coordinator to discuss 
recruitment, logistics for 
equipment storage, monitoring 
schedule 
Clinical /support staff 
• 
Emergency, 
• 
Product overview 
• 
Implant overview 
• 
Protocol overview 
• 
Practical “get to know” 
equipment session 
training (as appropriate) 
• 
Intensive care 
• 
Coronary care 
• 
Cardiothoracic surgical ward 
• 
Cardiac ward 
• 
Operating Room 
• 
Physiotherapy 
• 
Nutrition 
• 
Occupational Therapy 
• 
Infectious Diseases 
• 
Patients Local EMT 
• 
Patients Primary Caregivers 

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PROTOCOL DEVIATIONS 
 
A Protocol Deviation is defined as an event where the clinical investigator or site 
personnel did not conduct the study according to the investigational plan, protocol or the 
investigator agreement. 
Prior notification to the study manager is expected in those situations in which the 
investigator anticipates, contemplates, or makes a conscious decision to depart from the 
procedure specified in the Investigation Plan, except when necessary to protect the life or 
the physical well-being of a patient in an emergency. Prior notification is required in 
situations where the unforeseen circumstances are beyond the control of the Investigator 
(e.g. inadvertent mistakes, equipment failure, patient ill and unable to perform testing, 
etc.). 
Protocol deviations must be recorded on the Protocol Deviation eCRF. Include a 
description of the deviation, justification for the deviation, corrective action and whether 
the clinical manager was notified prior to the deviation. 
Deviations will be reported to the clinical manager regardless of whether medically 
justifiable, pre-approved by the clinical manager or taken to protect the patient in an 
emergency. Protocol deviations should be reported as soon as possible upon notification 
of the deviation. Study deviations may be discovered through variety of sources, such as 
during the data review, telephone conversations, and site monitoring. Report protocol 
deviations to your IRB in accordance with IRB policies and/or local laws. 
FDA regulations require the investigators to notify the sponsor and reviewing IRB within 
5 working days for the following deviations: 
Deviation from the investigational plan to protect the life or physical well– 
being of a patient in an emergency. 
“An investigator shall notify the sponsor and the reviewing IRB (see 56.108(a)(3) 
and (4) of any deviation from the investigational plan to protect the life or physical 
well–being of a patient in an emergency. Such notice shall be given as soon as 
possible, but in no event later than 5 working days after the emergency occurred.” 
812.150(a)(4) 
No informed consent prior to device use. 
“If an investigator uses a device without obtaining informed consent, the 
investigator shall report such use to the sponsor and the reviewing IRB within 5 
working days after the use occurs” (21 CFR 812.150(a)(5)) 

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A Protocol Deviation eCRF is to be completed for each study protocol deviation, 
including but not limited to: 
• Failure to obtain informed consent 
• Incorrect version of informed consent document used 
• Patient did not meet inclusion/exclusion criteria 
• Missed follow–up visit 
• Follow–up visit out of window 
• Failure to adhere to protocol required testing 
• IRB approval not obtained prior to implant 
• Implant occurring during IRB lapse of approval 
The following will not be considered protocol deviations: 
• Minor titration of cardiovascular medication regimen including: 
• Any downward titration of medications less than 50% of initial dose 
• Any upward titration of medication greater than 100% of initial dose 
• ACE/ARB may be added after implantation if tolerated 

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RECORDS AND REPORTS 
 
INVESTIGATIONAL RECORDS 
 
 
The investigator is responsible for the preparation (review and signature) and retention of 
all records cited below. All of the below records, with the exception of case history 
records, should be kept in the Investigator Site File, i.e., the study binder provided to the 
investigator. The following records are subject to inspection and must be retained for a 
period of two year (or longer as local law requires) after the study closure. 
• All correspondence that pertains to the investigation. 
• Patient’s case history records, including the signed patient informed consent form; 
all relevant observations; observations of adverse events; medical history; implant 
and follow–up data; documentation of the dates and reasons for any deviations 
from the protocol. 
• Device & Equipment Disposition Logs, containing Site delivery dates of devices, 
implant dates and returned to Sponsor dates, quantities and serial numbers of 
devices delivered at the site, quantities and serial numbers of devices returned to 
Sponsor, expiration dates and patient IDs of the patients implanted. 
• Signed Clinical Trial Agreement and current curriculum vitae. 
• IRB documentation and correspondence. 
• Center personnel training documentation forms. 
 
INVESTIGATOR REPORTS 
 
 
The investigator is responsible for the preparation (review and signature) and submission 
to the sponsor of all eCRFs, all death and adverse events (except unavoidable adverse 
events) and any deviations from the investigational plan; other reports are listed in Table 
6Table 6. All reports are subject to inspection and to the retention requirements described 
above for the investigator records. 
If an IRB takes any action as a result of this study, copies of all pertinent documentation 
must be forwarded to the sponsor. 

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Table 6.  Investigator Reports 
 
Report 
Submit to: 
Description 
Unanticipated Adverse 
Sponsor and IRB 
If an unforeseen complication 
Device Effect 
is determined to be related to 
the device, this information 
must be reported to FDA, IRB, 
and Sponsor. 
Withdrawal of IRB 
Sponsor 
The investigator must report a 
Approval 
withdrawal of the reviewing 
IRB approval within 5 working 
days. 
Progress Report 
Sponsor and IRB 
The investigator must submit 
this report if the study lasts 
more than one year on an 
annual basis. 
Deviation from the 
Sponsor and IRB 
The IRB and sponsor must be 
Investigational Plan 
notified within 5 working days 
of the event of an emergency 
deviation from the IP to protect 
the life or physical well–being 
of a patient. Except for the 
deviations under emergencies, 
prior notification must be 
submitted to Sunshine Heart. 
Failure to Obtain Informed 
Sponsor and IRB 
The investigator must make 
Consent 
notification within 5 working 
days after device use. The 
report must include a brief 
description of the 
circumstances justifying the 
failure to obtain informed 
consent and include written 
concurrence by a licensed 
physician not involved in the 
investigation. 
Final Report 
Sponsor and IRB 
A final report must be 
submitted within 3 months 
after termination or completion 
of the study. 

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SPONSOR RECORDS 
 
 
Sunshine Heart will retain the following records: 
• All correspondence which pertains to the investigation. 
• Device disposition records containing site delivery date of device, implant device 
serial numbers, expiration dates, quantities of devices shipped and returned. 
• Signed Clinical Trial Agreements, financial disclosure forms, and recent CV of 
investigators. 
• All adverse events (except unavoidable adverse events), deaths and complaints. 
• All eCRFs that are submitted, samples of the informed consents, investigational 
plans, and report of prior investigations. 
 
SPONSOR REPORTS 
 
 
Table 7. Sponsor Reports 
Report 
Submit to: 
Description 
Unanticipated 
FDA, all IRBs and 
Sunshine Heart will report any and all unanticipated 
Adverse Event – 
all Investigators 
device-related adverse event evaluation within 10 
Device Related 
working days of receipt of notice. 
Withdrawal of IRB 
FDA, all IRBs and 
Notification will be made within 5 days. 
Approval 
all Investigators 
Withdrawal of FDA 
All IRBs and 
Notification will be made within 5 working days. 
Approval 
Investigators 
Current Investigator 
FDA 
Sunshine Heart will submit a list of names and 
List 
addresses of all participating investigators at 6- 
month intervals (starting at 6-month after FDA 
approval). 
Progress Report 
FDA, all IRBs and 
A progress report will be submitted at least yearly. 
all Investigators 
Recall and 
FDA, all IRBs and 
Notification will be made within 30 working days 
Disposition 
all Investigators 
and will include the reasons for any request that an 
investigator return, repair or otherwise dispose of 
any devices. 
Final Report 
FDA, all IRBs and 
Sunshine Heart will notify FDA within 30 working 
all Investigators 
days of the completion or termination of the 
investigation. A final report will be submitted 
within 6 months after completion or termination. 
Failure to Obtain 
FDA/IRB 
A copy of the investigator’s report will be submitted 
Informed Consent 
within 5 working days of the notification. 

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PUBLICATION STRATEGY 
 
Sunshine Heart will form a publication committee that includes participating investigators. 
The committee will finalize a publication plan. The scientific validity and timing of 
publications will be evaluated in order to maximize the benefits derived from the 
publication of the North American clinical data of the study. In general, publications 
utilizing worldwide data will be managed as described below. 
 
PUBLICATION COMMITTEE 
 
 
The publication committee will be defined by the time enrollment for the primary 
objective is completed. Sunshine Heart will form a publication committee that includes 
participating investigators, the VP of Clinical Studies, and other Sunshine Heart 
personnel. 
The publication committee is responsible for overseeing the development of case reports, 
manuscripts, and abstracts according to the Publication Strategy, identifying and 
appointing the manuscripts/abstracts first author(s)/writer(s) and identifying Sunshine 
Heart personnel responsible for assisting the first author. The publication committee will 
meet approximately annually to refine the publication strategy. 
The publication committee reviews not only the main publications, but also ancillary 
publications. If necessary, specified authorship criteria may be applied for ancillary 
publications. The Committee may decide that no case reports, publications or abstracts 
will be prepared prior to the end of the study, or not on individual center data. 
Being a member of the subcommittee gives no privileges for authorship selection. 
Centers will be appraised of the objectives of the Publication Committee. Participating 
centers will agree that publication of the aggregate data from this multi-center trial takes 
precedence over results from an individual center. 
 
AUTHORSHIP SELECTION 
 
 
The first author will be selected on the basis of the following: 
• A significant contribution to the design of the study and/or development of the 
product; 
• A significant contribution to patient enrollment into the study; 
• High procedure volume and high quality of data as determined by the clinical 
study requirements; 
• Demonstration of a high level of interest in the performance of the product and/or 
the unique product features, applications, and the ability to write, review, edit, and 
present the publication; 
• A demonstration of a good publication history; 
• A willingness to contribute to the publication; 

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Appropriate geographic representation if a geographic region enrolls a significant number 
of patients. The Publication Committee recommends the number of authors per region. 
Appropriate Sunshine Heart personnel or representatives (e.g. clinical study personnel, 
statistician, and field personnel) are considered based on substantive contributions to the 
study or publication effort. 
All investigators not listed as co-authors will be acknowledged as the “Sunshine Heart 
C-Pulse® Investigators” and will be individually listed according to the applicable 
scientific journal. 
 
REVIEW AND COMMUNICATION GUIDELINES 
 
 
Investigators will receive a communication regarding the authorship selection, the 
publication co-authors and to which scientific platform the publication will be submitted. 
Prior to the submission of a publication (abstracts and manuscripts), the Sunshine Heart 
study team, publication committee and all co-authors will review and approve the contents 
and scientific platform. No individual center or individual investigator publications will 
be permitted for the Sunshine Heart C-Pulse® study unless agreed upon by the Publication 
Committee, to ensure consistency of methods, data integrity, and appropriate publication 
timing. 
Investigators who contribute patient data will be provided a copy of the final 
manuscript/abstract. 
For publication of investigator’s own data, Sunshine Heart will limit its review to a 
determination of whether or not confidential information is disclosed or if technically 
incorrect statements are made and will not attempt to censor the data or conclusions. 
 
ANCILLARY PUBLICATIONS 
 
 
The publication committee will review ancillary requests. Ancillary publications include 
those reporting on a subset of the patient population or reporting a specific aspect of the 
study. 
Requests for publications using regional data beyond the North American results will be 
evaluated for scientific validity and the ability of Sunshine Heart to provide resources. 
The publication committee must approve requests and will need to ensure that requests do 
not present conflicts with other geographical regions. If multiple geographies contribute 
to data, co-authorship will be representative, using the guideline for authorship selection 
described above. 

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APPENDIX A: ABBREVIATIONS AND ACRONYMS 
 
 
 
CEC 
Clinical Events Committee 
MAB 
Medical Advisory Board 
AE 
Adverse Events 
DSMB 
Data Safety and Monitoring Board 
HF 
Heart Failure 
ECG 
Electrocardiogram 
BTT 
Bridge to transplant 
VAD 
Ventricular Assist Device 
TTE 
Transthoracic echocardiography 
FDA 
Food and Drug Administration 
TEE 
Transesophageal echocardiography 
CRT 
Cardiac Resynchronization Therapy 
NYHA 
New York Heart Association 
QOL 
Quality of Life 
LVAD 
Left Ventricular Assist Device 
DT 
Destination Therapy 
IAB 
Intra Aortic Balloon 
IDE 
Investigational Device Exemption 
ICP 
Implantable Counterpulsation Pump 
PIL 
Percutaneous Interface Lead 
IR 
Infra–red 
CPX 
Cardiopulmonary Exercise Testing 
IRB 
Investigational Review Board 
MLWHF 
Minnesota Living With Heart Failure 
KCCQ 
Kansas City Cardiac Quality of Life Questionnaire 
CXR 
Chest Xray 
ECHO 
Echocardiogram 
eCRF 
Electronic Case Report Form Template 
ICU 
Intensive Care Unit 
IV 
Intra–venous 
PRBC 
Packed Red Blood Cells 
 

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APPENDIX B: NATIONAL CO–PRINCIPAL INVESTIGATORS 
 
 
The following physician–investigators have been designated as Principal Investigators for this 
study: 
 
William T. Abraham, M.D. 
Chief of Cardiovascular Medicine 
Ohio State University 
Division of Cardiovascular Medicine 
Room 110P DHLRI 
473 W. 12th Ave. 
Columbus, OH 43210–1252 
Patrick McCarthy, M.D. 
Chief, Division of Cardiothoracic 
Surgery 
Co–Director, Bluhm Cardiovascular 
Institute 
Heller–Sacks Professor of Surgery 
Northwestern University Feinberg 
School of Medicine 
201 East Huron Street, Galter 11–140 
Chicago, IL 60611–2968 

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APPENDIX C: PARTICIPATING INSTITUTIONS 
 
Up to 9 centers in the US and potentially some OUS centers will participate in the study. The 
following table represents the centers proposed for investigational sites. 
 
Site Name/Co-Principal & Principal 
Investigators 
Investigator Contact Info 
Ohio State University Medical Center 
Principal Investigator: 
Garrie Haas, MD (HFC) 
Ohio State Heart Center 
473 West 12th Ave, Suite 200 DHLRI 
Columbus, OH 43210-1252 
Ph (614) 293-4967 
Fax (614) 247-7789 
Northwestern University 
Feinberg School of Medicine 
Principal Investigator: 
Edward C. McGee, Jr.MD (CTS) 
Northwestern University Feinberg School of Medicine 
Bluhm Cardiovascular Institute 
201 East Huron Street, Galter 11-120 
Chicago, Illinois 60611-2968 
Ph (312) 695-3121 
Fax: (312) 695-1903 
Penn State Hershey Medical Center 
Principal Investigator: 
Walter Pae, MD (CTS) 
Penn State Milton S. Hershey Medical Center 
Division of Cardiology, H047 
500 University Drive, Room H1511 
Hershey, PA 17033-0850 
Ph (717) 531-8329 
Fax: (717) 531-8521 
University of Alabama at Birmingham 
Principal Investigator: 
Salpy Pamboukian, MD (HFC) 
Division of Cardiothoracic Surgery 
University of Alabama at Birmingham 
760 THT, 1900 University Blvd. 
Birmingham, AL 35294 
Ph: (205) 934-5486/ (205) 934-3368 
Fax: (205) 975-2553 
University of Louisville Jewish 
Hospital 
Principal Investigator: 
Sumanth Prabhu, MD (HFC) 
University of Louisville-Jewish Hospital 
201 Abraham Flexner Way, Suite 1200 
Louisville, KY 40202 
Ph (502) 629-2555 
Fax (502)-629-2551 
United Heart and Vascular Clinic 
Principal Investigator: 
Alan Bank, MD (HFC) 
Allina Hospital and Clinics 
2925 Chicago Ave 
Minneapolis, MN 55407 
Saint Luke’s Hospital – Mid America 
Heart Institute 
Principal Investigator: 
Sanjeev Aggarwal, MD (CTS) 
Saint Luke’s Hospital of Kansas City 
4401 Wornall Road 
Kansas City, MO 64111 
To be determined – will provide in 
Progress Report once IRB approval 
received 
To be determined 

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APPENDIX D: IRB LIST 
 
A list of the IRB contacts for each participating investigational center is included below. 
 
Site Name/Principal Investigator 
Institutional Review Board 
IRB Chairperson 
Northwestern University 
Feinberg School of Medicine 
Principal Investigator: 
Edward C. McGee, MD (CTS) 
Northwestern University 
Office for the Protection of Research Subjects 
750 North Lake Shore Drive, Suite 700 
Chicago, Illinois 60611 
Darren R. Gitelman, MD 
Ohio State University Medical 
Center 
Principal Investigator: 
Garrie Haas, MD (HFC) 
Western Institutional Board (WIRB) 
3535 7th Avenue SW 
Olympia, WA 98502-5010 
Theodore D. Schultz, J.D. 
Penn State-Milton S. Hershey 
Medical Center 
Principal Investigator: 
Walter Pae, MD (CTS) 
Penn State College of Medicine 
Penn State Milton S. Hershey Medical Center 
Human Subjects Protection Office, 
Institutional Review Board 
Room ASB 1140 
600 Centerview Drive, PO Box 855 Hershey, 
Pennsylvania 17033-0855 
Kevin Gleeson, MD 
University of Louisville 
Jewish Hospital 
Principal Investigator: 
Sumanth Prabhu, MD (HFC) 
University of Louisville 
MedCenter One, Suite 200 
501 E. Broadway 
Louisville, KY 40202-1798 
Laura L. Clark, MD 
University of Alabama at 
Birmingham 
Principal Investigator: 
Salpy Pamboukian, MD (HFC) 
Western Institutional Board (WIRB) 
3535 7th Avenue SW 
Olympia, WA 98502-5010 
Theodore D. Schultz, J.D. 
United Heart and Vascular Clinic 
Principal Investigator: 
Alan Bank, MD (HFC) 
Allina Hospital and Clinics IRB 
2925 Chicago Ave 
Minneapolis, MN 55407 
Thomas Ducker, MD 
Saint Luke’s Hospital – Mid 
America Heart Institute 
Principal Investigator: 
Sanjeev Aggarwal, MD (CTS) 
Saint Luke’s Hospital of Kansas City 
4401 Wornall Road 
Kansas City, MO 64111 
Alan Forker, MD 

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APPENDIX E: SUMMARY OF PREVIOUS STUDIES 
 
Experience to date by Sunshine Heart provides evidence of safety and performance. These 
include: 
 
INTRA–OPERATIVE CLINICAL FEASIBILITY STUDY 
 
 
The aim of this study was to determine the safety and performance of a new method of 
non blood contacting counterpulsation utilizing an inflatable cuff (C-Pulse) around the 
ascending aorta. 
In 6 patients undergoing first time off pump coronary bypass surgery via sternotomy, the 
C-Pulse was secured around the ascending aorta and attached to a standard 
counterpulsation console. At baseline, and with 1:2 and 1:1 augmentation, hemodynamic 
and echocardiographic parameters of ventricular function and coronary flow were 
measured. High intensity transient signals (HITS) were measured using transcutaneous 
Doppler over the right common carotid artery. 
No complications occurred. 
With C-Pulse there was no significant change in heart rate and blood pressure, and no 
increase in HITS. There was a 67% increase in diastolic coronary blood flow (mean left 
main diastolic velocity time integral 15.3 cm unassisted vs 25.1 cm assisted, p<0.05). 
Measurements with transesophageal echocardiography, at baseline and with 1:1 
counterpulsation, demonstrated a 6% reduction in end diastolic area (p = NS), 16% 
reduction in end systolic area (p < 0.01), 31% reduction in LV wall stress (p < 0.05), and a 
13 % improvement in fractional area change (p < 0.005). It was concluded that C-Pulse 
counterpulsation augments coronary flow and reduces left ventricular afterload. 
 
LONG–TERM EXTRA–AORTIC BALLOON COUNTERPULSATION IN SHEEP 
 
 
This study was undertaken to examine the effect of chronic counterpulsation with C-Pulse 
on the integrity of the ascending aorta in sheep at 5 and 10 months. 
A pre-shaped cuff, consisting of a polyurethane balloon and polyester wrap, was 
implanted around the ascending aorta via a left mini-thoracotomy in 11 adult sheep. An 
endocardial ECG sensing lead was implanted via the right external jugular vein. The 
balloon’s gas line and the sensing lead were brought out percutaneously over the back and 
connected to a Datascope 90 IABP console. 
Sheep were counterpulsated for approximately five and ten months. Prior to post-mortem, 
intra-aortic ultrasound examination was completed to examine balloon function. 
Following euthanasia, an autopsy was conducted in all sheep; particular attention was paid 
to the heart, brain and kidneys. Detailed histology was completed on the heart and great 
vessels with the attached device, from each sheep. 

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Intra-aortic ultrasound showed each cuff to be inflating and deflating in a normal pattern 
following 5 and 10 months operation. Sheep were terminated at five months (6) and 10 
months (5). 
One sheep was euthanized at 5 months because it became ill over several days; at autopsy 
it was found to have a bacterial infection involving the cuff and the aorta resulting in a 
contained aortic rupture. In two other sheep (at 5 and 10 months, respectively) non- 
disruptive aortitis was noted at post-mortem and this was confirmed by microscopic 
pathology. 
Hence the thoracic aorta was assessed microscopically in 8 sheep; 4 at 5 months and 4 at 
10 months. Histology of the aortic wall at the root and arch appeared normal. Sections 
through the mid-ascending aortas revealed the peri-aortic implants were well incorporated 
by the adventitial peri-aortic tissues and that there was no disruption to the endothelial 
surfaces. Histology demonstrated that for each of the 8 sheep the intima and inner half of 
the media, measuring 0.6–0.9 mm thick, appeared normal. Findings in the outer one third 
to one half of the aortic wall included muscular atrophy, thin-walled blood vessels, 
petechial haemorrhages, small focal strips of coagulative necrosis (0.1–0.3 mm thick) and 
viable reparative tissue responses. Those at 10 months, displayed a recognizable 
reparative microvascular (arterial and venular) pattern with less necrosis than at 5 months. 
The changes were circumferential. While the cuffed aortic wall was thinner than the 
normal wall, there was no evidence of progressive damage to the inner media and intima 
when comparing results from sheep at 5 months to those at 10 months. 
In conclusion, the structural integrity of both the counterpulsation cuff and the inner wall 
of the ascending aorta enclosed by the cuff remained intact for 10 months. Intermittent 
ongoing focal areas of damage and repair in the outer media were related to the device. 
Infection was an important complication leading to aortic disruption in one case. The 
anatomical intimacy between aorta and pulmonary artery in the sheep is closer than that 
observed in humans, and the aorta is more friable. Also, in this sheep study the cuff was 
inflated to transmural pressure at least twice that considered for humans. 
 
PROSPECTIVE OBSERVATIONAL STUDY 
 
 
Following preclinical studies and the intra-operative clinical study, a prospective 
observational study of the C-Pulse in NYHA Class III–IV end-stage heart failure patients 
was undertaken. Endpoints were safety, quality of life and cardiac performance. Five 
patients aged 54–73 years underwent implantation. 
There were no hospital deaths. All patients were discharged to rehabilitation and/or home. 
All patients were able to tolerate the device being turned off for short periods. 
There was a mean improvement of one NYHA class at one month. The cardiac index was 
increased and systolic pulmonary artery pressure reduced. One patient died of progressive 
multi-organ failure at 3 months, and two required device removal at 5 & 7 weeks 
respectively due to mediastinitis – one subsequently died from persistent intrathoracic 
infection. One patient was successfully transplanted at one month and one was 
symptomatically and hemodynamically improved on the device at 6 months follow-up. 

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This latter patient developed an exit-site infection with Pseudomonas and died at 7 months 
of sepsis-related multi-organ failure. 
In this first human long-term experience, the C-Pulse was safely implanted and was able 
to be turned off for brief periods. C-Pulse provided important relief of heart failure 
symptoms and improved cardiac performance. Early infection is likely related to the 
implant procedure. The device, training, implant procedure and peri-operative care 
procedures have been modified to reduce infection risk. An expanded feasibility study is 
warranted. 

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APPENDIX F: LABELING AND OPERATOR MANUAL 
 
 
 
 
 
 
 
 
Not related to this change – not resubmitted. 

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APPENDIX G: SAMPLE HIPAA DISCLOSURE 
 
Authorization for the Use and Disclosure of Protected Health Information (HIPAA) 
C-Pulse® Implantable Counterpulsation Pump (ICP) US Feasibility Study 
Sponsor: 
 
 
Principal Investigator: 
 
Phone Number: 
 
 
This section is asking you to authorize the use and disclosure of your health information for the 
C–Pulse® Implantable Counterpulsation Pump (ICP) which is a Heart Assist Device Study. To do 
that you need to know: 
• The kind of health information about you that the study will collect and use; this 
information includes: 
- medical chart review 
- and laboratory test results; 
• The reasons that we are doing this study, which have been described to you earlier, can be 
found in the Informed Consent section “Why Is This Study Being Done?” 
- Dr. <insert site PI, or whoever may replace this doctor> and the research staff are 
responsible for collecting this information here at <insert institution name>. 
- This clinical site will send your information on a form to the sponsor, which 
maintains of the database for the study. 
- Investigators for study, including representatives from the sponsor, will use your 
information to better understand how the C–Pulse® improves or does not improve 
life for heart failure patients, but they will not use your name or social security 
number. 
- The investigator and sponsor who make sure that your rights and safety are 
protected and that study findings are accurate may also need to see information 
about you in your records. 
• This authorization will end at the end of this study when all the information has been 
evaluated. 
• You can stop the use of your information in this research study by sending a written 
request to Dr. (insert name of PI). If you decide to withdraw your authorization: 
- No more information will be collected from you or your records for the research 
study from the time the written request is received; 
- The study will only use the information it has already collected from you before 
you sent the written request. 

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• When you sign this document and authorize the use and disclosure of your health 
information for this research, the information disclosed may no longer be protected by the 
federal privacy regulations found at 45 CFR Part 164. But, the researchers for this study 
can only use or disclose your health information for purposes that are approved by an 
Institutional Review Board or as required by law or regulation. 
 
 
Note: This consent form with the original signatures MUST be retained on file by the 
principal investigator. A copy must be given to the volunteer. A copy should be placed in the 
volunteer’s medical record, if applicable. 
Date 
PI or Designee Signature 
PI or Designee Name (print) 
PI or Designee’s Statement: 
I have reviewed the authorization for the use and disclosure of protected health information 
with the patient. To the best of my knowledge, she understands the meaning of this 
authorization. 
Date 
Witness Signature 
Witness Name (print) 
Date 
Participant Signature 
Participant Name (print) 
STATEMENT OF CONSENT 
(NOTE: This is only a suggested signature format. Sites may use their own signature page.) 
The details of this authorization have been explained to you and you have been given the 
opportunity to ask any questions you wish. 
If you voluntarily agree to allow the researchers to use and disclose your health information 
for the purpose of this study, please print and sign your name below. 

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APPENDIX H: SAMPLE INFORMED CONSENT 
 
SAMPLE OF INFORMED CONSENT 
FOR INVESTIGATIONAL RESEARCH STUDY 
 
PROTOCOL TITLE: 
C-Pulse® Implantable Counterpulsation Pump (ICP) US 
Feasibility Study 
 
PROTOCOL NUMBER: 
 
INSTITUTION: 
[Institution] 
 
INVESTIGATOR: 
[Investigator] 
 
 
 
Introduction 
Your physician has recommended that you consider undergoing a surgical procedure to receive the 
C-Pulse® heart assist device to treat your heart failure. The C-Pulse device works to assist the heart 
to pump blood, rather than “replacing” the heart function, and can be safely turned on or off as 
required. 
 
Currently, heart transplantation is the only widely accepted treatment option for patients with heart 
failure resistant to standard medications. Mechanical heart assist devices, pumps that do all the 
work of the heart to pump blood around the body, are used in some patients as a bridge-to- 
transplant, and in other patients who are not suitable for heart transplant, as a long-term implant 
(otherwise known as “destination therapy”). Such blood-contacting heart pumps require extensive 
surgery to implant, and cannot be turned off without the risk of permanent injury to the patient or 
death. The C-Pulse ® device is a new heart-assist device that allows you to remain active and does 
NOT contact the blood, therefore, the device does not require the use of blood thinning medications. 
 
Purpose 
The purpose of this consent form is to provide you with information to decide whether to participate 
in this study. Before you consent, study procedures will be explained to you, as well as the possible 
risks and benefits associated with the study. You understand that you are being asked to take part 
in a clinical research trial. If you sign this form, you agree to participate in this study. 

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The purpose of this research study is to evaluate a new heart assistance device, known as C-Pulse 
device to assist your failing heart. The C-Pulse is an experimental device and is not approved by 
the Federal and Drug Administration (FDA) in the United States. The C-Pulse device is being 
studied to evaluate its safety and ability to provide your body with improved blood flow. This means 
that the sponsor is conducting this study in order to verify that the new C-Pulse device can safely 
and effectively improve heart function in people with ongoing heart failure and who are resistant to 
medications. If you agree and you are suitable for the study, your surgeon will perform an operation 
on you to connect the cuff of the device to the aorta (largest artery in your body that comes from 
your heart and supplies your body with blood), thread a lead from the outside of your heart and 
tunnel it through your skin over your abdomen and to the outside driver unit-that controls the 
operation of the system and is attached to a vest or carry bag that you will wear. 
It is important that you read and understand this consent form. It may contain words that you do 
not understand. Please ask your doctor to explain any words or information that you do not 
understand. Do not sign this consent form unless you have received answers to all of your questions. 
 
There will be up to 40 patients enrolled and implanted in this study in the United States and up to 
9 centers in the US and potentially some OUS centers. Your part in the study and follow-up visits 
are expected to last up to 8 years. 
 
Device Description 
The C-Pulse device is a new heart-assist device that allows you to remain active and does NOT 
contact the blood, therefore, you will not need blood thinning medications. The C-Pulse device 
works to assist the heart to pump blood, rather than “replacing” the heart function, and can be safely 
turned on or off as required. 
The C-Pulse Cuff is positioned around the ascending aorta, the main artery coming out of the heart 
that delivers blood to the body. The Cuff deflates just before the heart pumps blood, reducing the 
workload of the heart (Fig 1A), and the Cuff is timed to re-inflate in between heart beats, once the 
heart has finished ejecting blood and the aortic valve closes. During this latter period, as the heart 
is re-filling, the Cuff inflation acts like a second heart beat, producing a second surge of blood flow 
to the heart muscle and around the body (Fig 1B). Reducing the load on the heart and increasing 
the blood flow to the heart muscle are very important in assisting the heart to pump blood around 
the body. Keeping the device out of the bloodstream limits the difficulty of implantation of the 
device and allows the device to be turned on and off for short periods of time. 

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The C-Pulse device is intended as a permanent implant and for the duration of the study to be used 
for at least 20 hours per day. It is considered safe to turn the device off for short periods (up to 15 
minutes) though you may experience return of symptoms of heart failure such as shortness of breath 
or dizziness during the period the device is off. 
The implanted C-Pulse Cuff is intended to have an operational life of at least four years. The Driver 
is designed to detect any Cuff failure and alarm and stop pumping. The Cuff is expected to be able 
to be replaced if this is indicated. 
Screening Evaluation, Tests, and Procedures 
You are being asked to participate in some screening tests and procedures determine if you are 
eligible for the study. If you meet criteria based upon these evaluations, you may be eligible to 
participate in the study. If you do not meet these criteria, you will not qualify to participate in the 
study. Once you sign this consent form you will begin your screening tests and procedures. 
If, after discussing the screening test procedures with your doctor, you agree to participate in the 
screening, your doctor will need to get information from you to determine if you have any medical 
condition that could exclude you from the study, increase your risks of surgery or interfere with the 
therapy. Your evaluation may include the following; 
• Medical history 
• General physical exam 
• Recording of weight, heart rate/rhythm, blood pressure, respiratory rate 
• Documentation of medications 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fig 1A: C-Pulse Cuff deflates as the 
heart ejects blood, unloading the heart. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fig 1B: C-Pulse Cuff inflates as the heart 
refills with blood, giving a secondary pulse of 
blood to the body and heart muscle. 

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You will be asked to have a chest x-ray to determine the condition of your aorta (the largest artery 
in your body that comes from your heart and supplies your body with blood) and lungs to see if you 
have any hardened areas in your aorta or any lung problems that may be a risk to you if you receive 
the C-Pulse Cuff. If your chest x-ray indicates you have hardened areas in your aorta or your lungs 
are not clear, you will not need to go on with any further screening tests and procedures as you will 
not be able to participate in the study. 
If the chest x-ray indicates you have no hardened areas in your aorta and your lungs are clear, your 
doctor will ask you to have a more extensive procedure to determine the condition of your aorta 
called a computed tomography (CT) scan or CAT scan. This test is used to show by imaging in 
detail, sections of your aorta to determine if disease is present. This scan will be performed in the 
hospital or out-patient image center. You will be asked to lie on a narrow table that slides into the 
center of the scanner while x-ray beams rotate around your chest. You may be asked to hold your 
breath during image capture. You may need some medication to help you relax. You will also be 
given some medication as part of the test to make the images more clear. Your doctor will monitor 
your kidneys after the CT scan to check for any damage from the medication. If the CT scan 
indicates you have aortic disease, it may be a risk to you if you receive the C-Pulse Cuff, therefore, 
you will not need to go on with any further testing and will not participate in the study. 
Once the condition of your aorta has been determined to be suitable for the study by chest x-ray 
and the CT scan; you may go on to obtain more tests to determine if you are eligible for the study. 
If at any time during the testing you are not eligible for the study, your doctor will stop any 
further testing and you will not participate in the study. The following is a remaining list of 
procedures that you will be tested for to determine if you are eligible for the study. 
• CT scan of your head will follow the CT scan of your aorta. It is exactly like the CT 
scan of your aorta only the x-ray beams will rotate around your head. 
• Right heart catheterization is the passing of a thin tube (catheter) into the right side of 
the heart. The procedure is done to see blood movement through the heart and to monitor 
your heart’s function. An X-ray image will help the doctor see where the catheter is 
placed. The test can be done in the hospital or outpatient procedure center depending 
upon your hospitals requirements. The physician who will perform the catheterization 
will go over the risks with you before it is done. 
• Transthoracic echocardiogram, (ECHO of your chest and heart) a painless procedure 
where gel is placed on a transducer which is then goes on your chest to measure your 
heart chambers and function including the valves of your heart. 
• Complete two questionnaires relating to your quality of life (MLHF Score, KCCQ) and 
a questionnaire about how you feel (Fatigue Impact Scales) 
• A Neurological test called the National Institute of Health Stroke Score (NIHSS) and a 
test called the Modified Rankin will be done to assess your neurologic state 
• Complete two assessments (NYHA Classification, Six Minute Walk - to measure how 
far you can walk in 6 minutes) 
• Pregnancy test (if applicable) 

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• Cardiopulmonary test shows the maximum amount of oxygen your heart can provide to 
your muscles during constant activity. Doctors consider this a true measure of your 
heart’s ability to keep you going. This test requires special equipment so it is usually 
done in a special clinic or hospital. You will be asked to blow into a tube connected to 
a lung doctor’s machine first. They you will have small adhesive electrodes stuck to 
your chest and sides like for an EKG. The wires will attached to the electrodes will 
connect you to a heart monitor. You will stand on a treadmill or exercise bike and your 
blood pressure will be taken with a cuff. A padded clothespin is clamped over your 
nostrils so you cannot breathe except through your mouth. The treadmill starts slowly 
and speed will slowly increase until it is as fast as you can manage and you are not 
talking “comfortable”. This is a test where they want to push you hard. You will be 
monitored during the exercise closely. The test continues until you are unable to go on. 
• 
Blood tests 
 
Study Procedures 
If you meet all screening criteria for the study and after discussing the study with your doctor, you 
decide to participate in the study, you will be scheduled and prepared to undergo surgery. 
The following are a list of procedures you can expect during and after the surgery: 
During the implant procedure (2 hours) 
During surgery, a sternotomy (your breast bone will be cut open) will be performed and a cuff that 
has been correctly sized to your aorta will be wrapped around your aorta and activated to help assist 
the heart in pumping blood. 
The ascending aorta (the main blood vessel which carries blood ejected from the heart) is freed up. 
The pre-shaped inflatable C-Pulse® Cuff is wrapped around the aorta and a lead to sense the ECG 
(the electrical signals of the heart) is attached to your heart. 
The gas line and sensing lead are connected to a single tube that is tunneled under the skin and 
brought out through the skin over the abdomen. This tube has a connector that allows it to be 
connected to a Driver (Fig 1). The Driver is activated during surgery to ensure the device performs 
as expected. 
During the surgery, examination of your heart and aorta with an ultrasound probe 
Monitoring of arterial blood pressure 

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After the procedure and before you leave the hospital: 
All patients in the study will receive the device and it will be turned ON for the duration of the 
study. 
Following the surgery, the expected stay in Intensive Care is 2-3 days to ensure the device is 
functioning in time with the heart and there are no heart rhythm disturbances and that the blood 
pressures are stable. The stay on the ward is 7-14 days and discharge from the hospital will be 
judged on your medical condition, your ability to walk without aid for short distances and you and 
your care-giver being able to handle the Driver and look after the exit site dressings. Your will 
continue to take anti-heart failure medication under the guidance of the investigators and your 
cardiologist. Rehabilitation following surgery is important to ensure a good recovery and this will 
also involve a program of physical and nutritional guidance. 
Your doctor and medical team may teach you to disconnect from your device for short periods of 
time (no more than 15 minutes at a time). You will need to discuss this with your doctor. 
You will not leave the hospital until your doctor has decided that you are ready. Before you leave, 
your doctor will do the following: 
• Echocardiogram, (ECHO of your chest and heart) a painless procedure where jell is 
placed on a transducer which is then goes on your chest to measure your heart 
chambers and function including the valves of your heart. 
• A neurological consultation from a specialist that will assess your brain and reaction 
functions. 
Be sure that you understand the complete device information and personal care that you need to 
do at home. 
Fig 2: C-Pulse device with wearable driver unit. 

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1- Month Follow-up Visits 
• General physical examination (including blood tests) 
• Documentation of medications 
• Recording of weight, heart rate, blood pressure, respiratory rate 
• 
(ECHO of your chest and heart) 
• Complete Six Minute Hall Walk and NYHA Classification assessment 
• Complete 2 questionnaires relating to your quality of life (MLHF Score, KCCQ) and two 
questionnaires about how you feel (Fatigue Impact Scales) 
• A Neurological test called the National Institute of Health Stroke Score (NIHSS) and 
Modified Rankin will be done to assess your mental state* 
 
3- Month Follow-up Visits 
• General physical examination (including blood tests) 
• Documentation of medications 
• Recording of weight, heart rate, blood pressure, respiratory rate 
• Chest X-Ray 
• (ECHO of your chest and heart) 
• Complete NYHA Classification and Six Minute Walk-assessment to measure how far you 
can walk in 6 minutes) 
• Complete 2 questionnaires relating to your quality of life (MLHF Score, KCCQ) and two 
questionnaires about how you feel (Fatigue Impact Scales) 
• A Neurological test (NIHSS) and Modified Rankin will be done to assess your mental 
state 
 
6- Month Follow-up Visits 
• General physical examination (including blood tests) 
• Documentation of medications 
• Recording of weight, heart rate, blood pressure, respiratory rate 
• CT Scan. This test is used to show by imaging in detail, sections of your aorta to 
determine if disease is present. This scan will be performed in the hospital or out-patient 
image center. You will be asked to lie on a narrow table that slides into the center of the 
scanner while x-ray beams rotate around your chest. You will be asked to hold your 
breath during image capture. You may need some medication to help you relax 
• (ECHO of your chest and heart) 
• Chest X-Ray 
• A very fine tube (catheter) will be inserted into one of your blood vessel, either in your 
groin or neck, and passed into the right chamber of your heart to assess the pressures in 
your heart (right heart catheterization) 
• Complete NYHA Classification and Six Minute Walk-assessment to measure how far you 
can walk in 6 minutes) 
• Complete 2 questionnaires relating to your quality of life (MLHF Score, KCCQ) and two 
questionnaires about how you feel (Fatigue Impact Scales) 
• A Neurological test (NIHSS) will be done to assess your mental state 
• A Neurological test called the Modified Rankin 
• Walking test to measure your maximum limit for exercise (Peak O2 uptake) 

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Long term Visits 12, 18 Month and Annual Visits (from implant date) 
• General physical examination (including blood tests) 
• Documentation of medications 
• Recording of weight, heart rate, blood pressure, respiratory rate 
• (ECHO of your chest and heart) 
• Complete NYHA Classification and Six Minute Walk-assessment to measure how far you 
can walk in 6 minutes) 
• Complete 2 questionnaires relating to your quality of life (MLHF Score, KCCQ) and two 
questionnaires about how you feel (Fatigue Impact Scales) 
 
*If at any time during the study you experience a neurological adverse event you will have the 
NIHSS and the Modified Rankin collected 30 and 60 days after your event. 
After 10 years of annual visits or the study is closed, your participation in the study will be 
completed. 
 
Risks 
Screening Tests and Procedures 
There are some risks in going through the screening tests and procedures and are described below: 
• Drug reactions to any pre-medications you might receive before the CT scan or right heart 
catheterization such as drowsiness, low blood pressure, nausea or vomiting. 
• For the right heart catheterization you may experience the following; 
o Bruising around the area where the catheter was inserted 
o Injury to the vein 
o Puncture to the lung if the neck or chest veins are used 
o rare complications could include cardiac arrhythmias, cardiac tamponade (pressure 
on your heart due to fluid build-up in the sac around your heart), low blood pressure, 
infection, or embolism (blocking an artery)caused by blood clots at the tip of the 
catheter. 
o Before the heart catheterization test, your doctor will review all the risks associated 
with the test 
• For the pulmonary testing, you may experience the following; 
o Very dry throat as well as excessive drooling 
o fatigue 
• Possible infection at the needle puncture site from the right heart catheterization or blood 
tests 
• Exposure to x-ray 

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Study Risks 
There are several risks associated with participating in this study listed below. Risks in this study 
may come from the surgical procedure itself, implantation procedure or the investigational device. 
Your study doctor will discuss them with you. 
General Anesthetic (1-5%) 
• Drug reactions 
• Low blood pressure 
• Difficulty with maintaining adequate oxygen to the body 
 
Surgical procedure: 
• Bleeding, possibly requiring blood transfusions, surgical or medical interventions 
• Infection possibly requiring surgical or medical intervention (e.g. intravenous medication, 
antibiotics) 
• Stroke or other neurologic event 
• Memory and thinking problems 
• Decrease or loss of kidney function, possibly requiring use of a machine to filter your 
blood 
• Irregular heartbeats 
• Fluid buildup around the heart 
• Damage to the aortic wall that may cause the layers of the aorta to separate 
• Device malfunction such as damage to the cuff, misplacement of the lead on the heart 
• Blood disorders 
• Abnormal liver function; digestion complications; fever or chills, organ failure or 
dysfunction 
• High blood pressure 
• Heart attack 
• Separation of your incision 
• Lack of sufficient oxygen to limbs or organs to support normal organ function 
• Partial or full blockage of your veins or arteries 
• Death 
 
C–Pulse® Heart Assist Device: 
• Lack of effect – the device may not provide relief from your heart failure symptoms if they 
are severe 
• Device failure – failure of the device to provide adequate support to relieve the symptoms 
of heart failure 
• Persistent leaking balloon may cause surgical emphysema (injury to the air sacs in 
the lung) or pneumothorax (abnormal collection of air in between the lung and chest 
wall) 
• Leakage of non-sterile air may cause pneumothorax or chest infection 
• Air emboli in the aorta 
• Needle puncture in the cuff 
• Failure of the electronic system to detect any system failure such as current leakage, 
voltages, power supply or over inflation of the cuff 

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• Infection – infection from the line that is tunneled thru your skin to the outside of your body 
may occur 
o Your doctor may perform additional testing that may expose you to radiation 
• Emboli – due to the repeated inflations of the cuff, small particles in your blood may come 
loose from the aortic wall causing a stroke 
• Aortic disruption- due to the repeated inflations of the cuff may cause a split in the aortic 
wall that may cause the layers of the aorta to separate 
• Worsening of heart failure symptoms-You may experience symptoms of heart failure, such 
as shortness of breath or dizziness 
• Death 
There may be additional risks which are unknown. Your doctor has been chosen to participate as 
an investigator in this study because he or she has the skills and knowledge to perform the study 
procedures and this should minimize your risk. 
If your doctor suspects that you have an infection from the line that is tunneled thru your skin to 
the outside of your body, additional tests may be requested. These tests may include blood tests for 
infection, CT or PET scans, to determine if the tube should be removed to let the infection heal. 
In the event of your death during the study, an autopsy may be requested. If an autopsy is performed, 
small pieces of your aorta may be collected for examination under a microscope. This may be 
requested regardless of whether you have had the C-Pulse System implanted for the study. If you 
had a device implanted, that device may be returned to the Sponsor for testing as well, if an autopsy 
is performed. 
If you are pregnant or plan to become pregnant or are nursing a baby, you cannot enter this study. 
There may be a risk of severe problems. Women may participate in this study only if they are past 
menopause, have had surgery to make them sterile, or are using an acceptable form of birth control 
throughout the course of the study. If you become pregnant during the trial, you must notify your 
doctor immediately. 
 
Benefits 
There is no guarantee that you will benefit from taking part in this study. The main benefit from 
participation in the study may be some improvement in your quality of life. It is not expected that 
there will be a complete restoration to a quality of life that you had before heart failure. 
The information from this study may also benefit future patients who are in moderate to severe 
heart failure. 
 
Alternatives 
The alternative to using this new device includes ongoing medication for alleviating the symptoms 
of heart failure. If symptoms persist, cardiac transplantation or mechanical blood pumps may be an 
option in some patients. The C- Pulse device is intended as a treatment option in patients who are 
ambulatory, on optimal medical therapy but continue to have a poor quality of life. 

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Voluntary Participation 
Your participation in this study is voluntary. You may choose whether you wish to be in this study 
and whether to remain in the study at all times after enrollment. If you withdraw from the study, 
you will not lose any benefits to which you are entitled. Your participation in the study may be 
stopped at any time by your doctor without your consent. If you withdraw or are withdrawn from 
the study for any reason, you may be asked to return to the clinic for a follow-up examination. 
You will be informed of any new information that may affect your decision to continue in the study. 
 
Termination 
This research project may stop for a variety of reasons. These may include reasons such as: 
unacceptable side effects, the device being shown not to be effective or not need further 
investigation; and decisions made in the commercial interests of the Sponsor. 
 
New information arising during the study 
During the study, new information about the risks and benefits of the device may become known 
to researchers and might alter your willingness to continue your participation in the study. If this 
occurs, you will be told about this new information. This new information may mean that you can 
no longer participate in this research. If this occurs, the person(s) supervising the research will stop 
your participation. In all cases, you will be offered all available care to suit your needs and medical 
condition. 
 
Cost 
Routine costs are those costs normally incurred as a result of medical care associated with the 
treatment of your heart failure condition. These costs are generally the patient’s responsibility or, 
where appropriate, the responsibility of your insurance company. You will not incur any additional 
costs as a result of your participation in this Study. 
 
Compensation 
You will not receive any compensation for participating in this study. 
 
Financial Arrangements with Sponsor 
As is usually the case for clinical trials that are sponsored by a manufacturing company, <Hospital> 
will receive payment from the Sponsor for each patient enrolled in this study. These payments will 
be used to defray the costs of data collected for the study. No hospital staff member will receive 
private income as a result of your enrollment in this study. 

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Injury 
In the event that physical or psychological injury occurs as a result of your participation in this 
research project, medical treatment will be available. This treatment, as well as other medical 
expenses, will be paid for by you or your health insurance in your usual manner. No compensation 
or  reimbursement  is available from  
(name of institution) , or the Sponsor, Sunshine 
Heart, Inc. 
If you are injured you should report the injury by contacting: 
 
 
(Principal Investigator) 
(Telephone number) 
 
Confidentiality 
If you agree to take part in this study, your medical records will be treated confidentially except as 
required by law. Access to your medical records will be limited to the medical staff at the study 
center, some qualified representatives from the sponsor, the Institutional Review Board (IRB) 
reviewing the study, and the US Food and Drug Administration (FDA). Nothing about you, your 
illness or treatment will be made public. If the results of this study are published, your identity will 
remain confidential. 
 
Study Questions 
If you have questions about the study, you may contact: 
 
 
(Principal Investigator) 
(Telephone number) 
 
Subject Rights 
If you have questions regarding the conduct of this study or your rights as a research subject, you 
may contact: 
 
 
Chairperson of the IRB 
(Telephone number) 
 
Permission for Access to and Use of Health Information 
If you decide to take part in the study, Sunshine Heart and others will see your health data. This 
section governs how your health data will be used and shared during and after the study. The health 
data that may be used and shared includes all data collected during the study and any health data in 
your medical records that is relevant to the study. 

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Providers’ Disclosure of Health Information in Your Medical Records 
You agree to permit [hospital and/or clinic], your doctors, and your other health care providers 
(“Providers”) to share health data in your medical records with [investigator(s)] and 
[his/her/their/its] staff (“Researchers”). You agree to permit Providers to share your health data: 
• With Sunshine Heart and its agents and contractors 
• As required by law 
• With government organizations and review boards required to watch over the safety and 
effectiveness of medical products and therapies and the conduct of research 
• With other persons who are required to watch over the safety and effectiveness of 
medical products and therapies and the conduct of research 
 
Researchers’ User and Disclosure of Your Health Information 
You agree to permit the Researchers to use and share your health data 
• Among themselves to conduct the study 
• With other researchers in the study 
• With Sunshine Heart 
• With government organizations and review boards required to watch over the safety and 
effectiveness of medical products and therapies and the conduct of research 
• With other persons who are required to watch over the safety and effectiveness of 
medical products and therapies and the conduct of research 
Once Providers or Researchers have shared your health data with a third party, the data may be 
subject to further sharing by the third party. Federal privacy laws may no longer protect it from 
further sharing. 
While the study is in progress, you will not be allowed to see your health data that is created or 
collected for the study. After the study is done, you may see this data as in the [hospital/clinical 
trial sits]’s Notice of Information practices. 
 
Sunshine Heart User and Disclosure of Your Health Information 
This section describes what Sunshine Heart will do with the study data. This includes your health 
data received during the study. 
Sunshine Heart will keep your health data confidential in keeping with all applicable laws. Sunshine 
Heart may use your health data to conduct this study. Sunshine Heart may use your health data for 
other purposes, such as: 
• Watch over and improve the device performance 
• New medical research 
• Plans for making new medical products or procedures 
• Other business purposes 
Any reports about the study will not include your name or a description of you. Data received during 
the study will not be used to market to you. Your name will not be placed on any mailing lists or 
sold to anyone for marketing purposes. 

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Your Country’s regulations and other laws control Sunshine Heart’s work in making new devices. 
These laws help make certain the safety and quality of medical devices. Sunshine Heart may share 
your health data with the United States Food and Drug Administration (FDA) or other US and 
foreign government authorities that are responsible for the safety of medical devices. Sunshine 
Heart may share your health data with institutional review boards and persons who watch over 
research and the safety and effectiveness of medical products and research. You agree to allow 
Sunshine Heart to use study data in these ways. 
This consent does not have an ending date. But you may change your mind and take back this 
consent to use your health data at any time. To take back this consent, you must write to [name and 
contact information]. If you take back this consent, you cannot take part in the study. Even after 
your part in the study ends, Sunshine Heart and Researchers may continue to use and share the 
health data they got during the study as described here. 
 
Consent 
I have read the information in this consent form (or it has been read to me). 
I have had an opportunity to discuss with my study doctor the purpose, methods, risks and potential 
benefits of this research as well as available alternatives, and to ask questions regarding my 
participation in this research. My questions have been answered to my satisfaction. 
My participation in this research is voluntary. I agree to participate in this research study. By signing 
this consent form, I have not given up any of my legal rights. 
I will be given a copy of this informed consent form. 

 
 

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Authorization 
I have been given the information about the use and disclosure of my health information for this 
research study. My questions have been answered. 
 
I authorize the use and disclosure of my health information to the parties listed in the authorization 
section of this consent for the purposes described above. 
 
 
 
Signature of Subject 
Date/Time 
 
 
 
Print Name of Subject 
 
 
 
Subject’s Legal Representative Signature (if applicable) 
Date/Time 
 
 
 
Printed Name of Subject’s Legal Representative (if applicable) 
 
 
 
Investigator Signature (or Designee) 
Date/Time 
 
 
 
Printed Name of Investigator (or Designee) 

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APPENDIX I: REQUIRED TESTS 
 
 
 
Follow-up Requirements Baseline to 6 months Post Implant 
Pre- 
Implant 
Implant 
Pre- 
Discharge7 
1 mo 
3 mo 
6 mo 
A. PATIENT ELIGIBILITY 
X 
B. GENERAL 
Demographic Data 
X 
Medical History 
X 
General Physical Examination 
X 
X 
X 
X 
X 
X 
Concurrent Medications 
X 
X 
X 
X 
X 
X 
Pregnancy test (if applicable) 
X 
C. VITAL PARAMETERS 
Weight 
X 
X 
X 
X 
X 
Heart rate 
(ECG pre-implant) 
X 
X 
X 
X 
X 
Blood pressure 
X 
X 
X 
X 
X 
Respiratory rate 
X 
X 
X 
X 
X 
D. CARDIOPULMONARY 
CT aorta 
X 
X 
CXR 
X 
X 
X 
ECHO 
X 
X2 
X 
X 
X 
Right heart catheterization 
(CVP, PAP, CI, PCWP, SVR, PVR) 
X 
X 
Peak O2 uptake 
X 
X 
E. QUALITY OF LIFE 
NYHA Classification 
X 
X 
X 
X 
MLHF Score/ KCCQ 
X 
X 
X 
X 
Fatigue Impact Scales 
X 
X 
X 
X 
X 
Six Minute Walk 
X 
X 
X 
X 
F. HEMATOLOGY 
Hemoglobin 
X 
X 
X 
X 
X 
Hematocrit 
X 
X 
X 
X 
X 
Plasma free hemoglobin 
X 
X 
X 
X 
X 
Platelet count 
X 
X 
X 
X 
X 
White cell count 
X 
X 
X 
X 
X 
APTT 
X 
X 
X 
X 
X 
INR 
X 
X 
X 
X 
X 
Fibrinogen 
X 
X 
X 
X 
X 
G. BIOCHEMISTRY 
Serum sodium 
X 
X 
X 
X 
X 
Serum potassium 
X 
X 
X 
X 
X 
Serum creatinine/ GFR3 
X 
X 
X 
X 
X 
BUN 
X 
X 
X 
X 
X 
Serum albumin 
X 
X 
X 
X 
X 
Serum bilirubin 
X 
X 
X 
X 
X 

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Follow-up Requirements Baseline to 6 months Post Implant 
Pre- 
Implant 
Implant 
Pre- 
Discharge7 
1 mo 
3 mo 
6 mo 
Serum ALT 
X 
X 
X 
X 
X 
Serum AST 
X 
X 
X 
X 
X 
Serum BNP 
X 
X 
H. NEUROLOGICAL 
ASSESSMENT6 
Neurological testing (NIHSS)4 
X 
X 
X 
X 
X 
Modified Rankin 4 
X 
X 
X 
X 
X 
Head CT 5 
X 
Neurological Consultation 
X 
X6 
I. IMPLANT DETAILS 
X 
J. DEVICE LOG 
X 
X 
X 
X 
K. DISCHARGE 
CHECKLIST 
X 
1 Annually post-implant 
2 Epi-aortic Echo at implant 
3 Estimated GFR at Baseline and within one week post CT to evaluate contrast induced nephropathy. 
4 Post Neurological Dysfunction AE – 30, 60 and 90 days post event 
5 At Baseline only or as clinically indicated with any Neurological Dysfunction AE – Head CT should be completed only after clearance 
for implantation. 
6 Required at 5-7 days post ICU discharge or at hospital discharge whichever occurs first and at the time of any suspected Neuro 
Dysfunction AE 
7 At Discharge - (see Appendix M) 
 
 
Long-term Post Implant Follow-Up Requirements 
12 month 
18 month 
Annually 
Year 2-10 
A. PATIENT ELIGIBILITY 
B. GENERAL 
General Physical Examination 
X 
X 
X 
Concurrent Medications 
X 
X 
X 
Pregnancy test (if applicable) 
C. VITAL PARAMETERS 
Weight 
X 
X 
X 
Heart rate 
(ECG pre-implant) 
X 
X 
X 
Blood pressure 
X 
X 
X 
Respiratory rate 
X 
X 
X 
D. CARDIOPULMONARY 
ECHO 
X 
X 
X 
E. QUALITY OF LIFE 
NYHA Classification 
X 
X 
X 
MLHF Score/ KCCQ 
X 
X 
X 
Fatigue Impact Scales 
X 
X 
X 
Six Minute Walk 
X 
X 
X 
F. HEMATOLOGY 
Hemoglobin 
X 
X 
X 
Hematocrit 
X 
X 
X 

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Long-term Post Implant Follow-Up Requirements 
12 month 
18 month 
Annually 
Year 2-10 
Plasma free hemoglobin 
X 
X 
X 
Platelet count 
X 
X 
X 
White cell count 
X 
X 
X 
APTT 
X 
X 
X 
INR 
X 
X 
X 
Fibrinogen 
X 
X 
X 
G. BIOCHEMISTRY 
Serum sodium 
X 
X 
X 
Serum potassium 
X 
X 
X 
Serum creatinine/ GFR3 
X 
X 
X 
BUN 
X 
X 
X 
Serum albumin 
X 
X 
X 
Serum bilirubin 
X 
X 
X 
Serum ALT 
X 
X 
X 
Serum AST 
X 
X 
X 
I. IMPLANT DETAILS 
J. DEVICE LOG 
X 
X 
X 
K. DISCHARGE CHECKLIST7 
1 Annually post-implant 
2 Epi-aortic Echo at implant 
3 Estimated GFR at Baseline only 
4 Post Neurological Dysfunction AE – 30, 60 and 90 days post event 
5 At Baseline only or as clinically indicated with any Neurological Dysfunction AE – Head CT should be completed 
only after clearance for implantation. 
6 Required at 5-7 days post ICU discharge or at hospital discharge whichever occurs first and at the time of any 
suspected Neuro Dysfunction AE 
7 At Discharge (see Appendix M) 

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APPENDIX J: CORE LABORATORIES 
 
Cardiopulmonary Exercise Testing 
Henry Ford Health System 
Clinical Exercise Physiology Core Lab 
6525 Second Ave 
Detroit, MI 48202 
 
Voice: (313) 972-1920, FAX: (313) 972-1921 
cepcorelab@hfhs.org 
 
 
Primary Contact: Clinton Brawner 
 
Echocardiography 
Cardiovascular Core Labs 
100 Irving Street, NW 
Suite EB-5123 
Washington, DC 20010 
 
Voice: (202)877-0223 
 
Primary Contact: Neil J Weissman, MD 
 
 
CT Scan 
Cardiovascular Core Labs 
100 Irving Street, NW 
Suite EB-5123 
Washington, DC 20010 
 
Voice: (202)877 6177 
 
Primary Contact: Wm Guy Weigold, MD 

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APPENDIX K: SAMPLE CASE REPORT FORMS 
 
Not related to this change – not resubmitted 

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APPENDIX L: NEUROLOGICAL TESTING 
 
NIH STROKE SCALE 
 
 
The NIH Stroke Scale (NIHSS) must be administered at Pre–implant Baseline and each follow– 
up. Administer the stroke scale items in the order listed. Record performance in each category 
after each subscale exam. Do not go back and change scores. Follow directions provided for 
each exam technique. Scores should reflect what the patient does, not what the clinical thinks 
the patient can do. The clinician should record answers while administering the exam and work 
quickly. Except where indicated the patient should not be coached (i.e. repeated requests to 
patient to make a special effort). 
 
 
Instructions 
Scale Definition 
1a. Level of Consciousness: The investigator must 
choose a response, even if a full evaluation is prevented 
by such obstacles as an endotracheal tube, language 
barrier, orotracheal trauma/bandages. A 3 is scored only 
if the patient makes no movement (other than reflexive 
posturing) in response to noxious stimulation 
0 = Alert; keenly responsive. 
1 = Not alert, but arousable by minor stimulation to obey, answer, or 
respond. 
2 = Not alert, requires repeated stimulation to attend, or is obtunded 
and requires strong or painful stimulation to make movements (not 
stereotyped). 
3 = Responds only with reflex motor or autonomic effects or totally 
unresponsive, flaccid, areflexic. 
1b. LOC Questions: The patient is asked the month 
and his/her age. The answer must be correct - there is 
no partial credit for being close. Aphasic and stuporous 
patients who do not comprehend the questions will 
score 2. Patients unable to speak because of 
endotracheal intubation, orotracheal trauma, severe 
dysarthria from any cause, language barrier or any other 
problem not secondary to aphasia are given a 1. It is 
important that only the initial answer be graded and that 
the examiner not "help" the patient with verbal or non- 
verbal cues. 
0 = Answers both questions correctly. 
1 = Answers one question correctly. 
2 = Answers neither question correctly. 
1c. LOC Commands: The patient is asked to open and 
close the eyes and then to grip and release the non- 
paretic hand. Substitute another one step command if 
the hands cannot be used. Credit is given if an 
unequivocal attempt is made but not completed due to 
weakness. If the patient does not respond to command, 
the task should be demonstrated to them (pantomime) 
and score the result (i.e., follows none, one or two 
commands). Patients with trauma, amputation, or other 
physical impediments should be given suitable one-step 
commands. Only the first attempt is scored. 
0 = Performs both tasks correctly 
1 = Performs one task correctly 
2 = Performs neither task correctly 
2. Best Gaze: Only horizontal eye movements will be 
tested. Voluntary or reflexive (oculocephalic) eye 
movements will be scored but caloric testing is not done. 
If the patient has a conjugate deviation of the eyes that 
can be overcome by voluntary or reflexive activity, the 
score will be 1. If a patient has an isolated peripheral 
nerve paresis (CN III, IV or VI) score a 1. Gaze is 
testable in all aphasic patients. Patients with ocular 
trauma, bandages, pre-existing blindness or other 
disorder of visual acuity or fields should be tested with 
reflexive movements and a choice made by the 
investigator. Establishing eye contact and then moving 
about the patient from side to side will occasionally 
clarify the presence of a partial gaze palsy. 
0 = Normal 
1 = Partial gaze palsy. This score is given when gaze is abnormal in 
one or both eyes, but where forced deviation or total gaze paresis are 
not present. 
2 = Forced deviation, or total gaze paresis not overcome by the 
oculocephalic maneuver. 

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Instructions 
Scale Definition 
3. Visual: Visual fields (upper and lower quadrants) are 
tested by confrontation, using finger counting or visual 
threat as appropriate. Patient must be encouraged, but if 
they look at the side of the moving fingers appropriately, 
this can be scored as normal. If there is unilateral 
blindness or enucleation, visual fields in the remaining 
eye are scored. Score 1 only if a clear-cut asymmetry, 
including quadrantanopia is found. If patient is blind from 
any cause score 3. Double simultaneous stimulation is 
performed at this point. If there is extinction patient 
receives a 1 and the results are used to answer question 
11. 
0 = No visual loss 
1 = Partial hemianopia 
2 = Complete hemianopia 
3 = Bilateral hemianopia (blind including cortical blindness) 
4. Facial Palsy: Ask, or use pantomime to encourage 
the patient to show teeth or raise eyebrows and close 
eyes. Score symmetry of grimace in response to 
noxious stimuli in the poorly responsive or 
noncomprehending patient. If facial trauma/bandages, 
orotracheal tube, tape or other physical barrier obscures 
the face, these should be removed to the extent 
possible. 
0 = Normal symmetrical movement 
1 = Minor paralysis (flattened nasolabial fold, asymmetry on smiling) 
2 = Partial paralysis (total or near total paralysis of lower face) 
3 = Complete paralysis of one or both sides (absence of facial 
movement in the upper and lower face) 
5 & 6. Motor Arm and Leg: The limb is placed in the 
appropriate position: extend the arms (palms down) 90 
degrees (if sitting) or 45 degrees (if supine) and the leg 
30 degrees (always tested supine). Drift is scored if the 
arm falls before 10 seconds or the leg before 5 seconds. 
The aphasic patient is encouraged using urgency in the 
voice and pantomime but not noxious stimulation. Each 
limb is tested in turn, beginning with the non-paretic arm. 
Only in the case of amputation or joint fusion at the 
shoulder or hip may the score be "9" and the examiner 
must clearly write the explanation for scoring as a "9". 
5a. Left Arm 
5b. Right Arm 
0 = No drift, limb holds 90 (or 45) degrees for full 10 seconds. 
1 = Drift, Limb holds 90 (or 45) degrees, but drifts down before full 10 
seconds; does not hit bed or other support. 
2 = Some effort against gravity, limb cannot get to or maintain (if cued) 
90 (or 45) degrees, drifts down to bed, but has some effort against 
gravity. 
3 = No effort against gravity, limb falls. 
4 = No movement 
9 = Amputation, joint fusion 
explain:  
 
6a. Left Leg 
6b. Right Leg 
0 = No drift, leg holds 30 degrees position for full 5 seconds. 
1 = Drift, leg falls by the end of the 5 second period but does not hit 
bed. 
2 = Some effort against gravity; leg falls to bed by 5 seconds, but has 
some effort against gravity. 
3 = No effort against gravity, leg falls to bed immediately. 
4 = No movement 
9 = Amputation, joint fusion, 
explain:  
 

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Instructions 
Scale Definition 
7. Limb Ataxia: This item is aimed at finding evidence 
of a unilateral cerebellar lesion. Test with eyes open. In 
case of visual defect, insure testing is done in intact 
visual field. The finger-nose-finger and heelshin tests 
are performed on both sides, and ataxia is scored only if 
present out of proportion to weakness. Ataxia is absent 
in the patient who cannot understand or is paralyzed. 
Only in the case of amputation or joint fusion may the 
item be scored "9", and the examiner must clearly write 
the explanation for not scoring. In case of blindness test 
by touching nose from extended arm position. 
0 = Absent 
1 = Present in one limb 
2 = Present in two limbs 
If present, is ataxia in Right arm 1 = Yes 2 = No 
9 = amputation or joint fusion, explain   
 
Left arm 1 = Yes 2 = No 
9 = amputation or joint fusion, explain   
 
Right leg 1 = Yes 2 = No 
9 = amputation or joint fusion, explain   
 
Left leg 1 = Yes 2 = No 
9 = amputation or joint fusion, explain   
 
7a. Right Arm: Ataxia present? 
7b. Left Arm: Ataxia present? 
7c. Right Leg: Ataxia present? 
7d. Left Leg: Ataxia present? 
1 = Yes 
2 = No 
9 = amputation or joint fusion, 
explain   
 
8. Sensory: Sensation or grimace to pin prick when 
tested, or withdrawal from noxious stimulus in the 
obtunded or aphasic patient. Only sensory loss 
attributed to stroke is scored as abnormal and the 
examiner should test as many body areas [arms (not 
hands), legs, trunk, face] as needed to accurately check 
for hemisensory loss. A score of 2, "severe or total," 
should only be given when a severe or total loss of 
sensation can be clearly demonstrated. Stuporous and 
aphasic patients will therefore probably score 1 or 0. 
The patient with brain stem stroke who has bilateral loss 
of sensation is scored 2. If the patient does not respond 
and is quadriplegic score 2. Patients in coma (item 
1a=3) are arbitrarily given a 2 on this item. 
0 = Normal; no sensory loss. 
1 = Mild to moderate sensory loss; patient feels pinprick is less sharp or 
is dull on the affected side; or there is a loss of superficial pain with 
pinprick but patient is aware he/she is being touched. 
2 = Severe to total sensory loss; patient is not aware of being touched 
in the face, arm, and leg. 
9. Best Language: A great deal of information about 
comprehension will be obtained during the preceding 
sections of the examination. The patient is asked to 
describe what is happening in the attached picture, to 
name the items on the attached naming sheet, and to 
read from the attached list of sentences. 
Comprehension is judged from responses here as well 
as to all of the commands in the preceding general 
neurological exam. If visual loss interferes with the tests, 
ask the patient to identify objects placed in the hand, 
repeat, and produce speech. The intubated patient 
should be asked to write. The patient in coma (question 
1a=3) will arbitrarily score 3 on this item. The examiner 
must choose a score in the patient with stupor or limited 
cooperation but a score of 3 should be used only if the 
patient is mute and follows no one step commands. 
0 = No aphasia, normal 
1 = Mild to moderate aphasia; some obvious loss of fluency or facility of 
comprehension, without significant limitation on ideas expressed or 
form of expression. Reduction of speech and/or comprehension, 
however, makes conversation about provided material difficult or 
impossible. For example in conversation about provided materials 
examiner can identify picture or naming card from patient's response. 
2 = Severe aphasia; all communication is through fragmentary 
expression; great need for inference, questioning, and guessing by the 
listener. Range of information that can be exchanged is limited; listener 
carries burden of communication. Examiner cannot identify materials 
provided from patient response. 
3 = Mute, global aphasia; no usable speech or auditory comprehension. 
10. Dysarthria: If patient is thought to be normal an 
adequate sample of speech must be obtained by asking 
patient to read or repeat words from the attached list. If 
the patient has severe aphasia, the clarity of articulation 
of spontaneous speech can be rated. Only if the patient 
is intubated or has other physical barrier to producing 
speech, may the item be scored "9", and the examiner 
must clearly write an explanation for not scoring. Do not 
tell the patient why he/she is being tested. 
0 = Normal 
1 = Mild to moderate; patient slurs at least some words and, at worst, 
can be understood with some difficulty. 
2 = Severe; patient's speech is so slurred as to be unintelligible in the 
absence of or out of proportion to any dysphasia, or is mute/anarthric. 
9 = Intubated or other physical barrier, 
explain  
 

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Instructions 
Scale Definition 
11. Extinction and Inattention (formerly Neglect): 
Sufficient information to identify neglect may be obtained 
during the prior testing. If the patient has a severe visual 
loss preventing visual double simultaneous stimulation, 
and the cutaneous stimuli are normal, the score is 
normal. If the patient has aphasia but does appear to 
attend to both sides, the score is normal. The presence 
of visual spatial neglect or anosagnosia may also be 
taken as evidence of abnormality. Since the abnormality 
is scored only if present, the item is never untestable. 
0 = No abnormality. 
1 = Visual, tactile, auditory, spatial, or personal inattention or extinction 
to bilateral simultaneous stimulation in one of the sensory modalities.  
2 = Profound hemi-inattention or hemi-inattention to more than one 
modality. Does not recognize own hand or orients to only one side of 
space. 
 
MODIFIED RANKIN 
 
 
The Modified Ranking must be administered at Pre–implant Baseline and each follow–up. 
Administer the stroke scale items in the order listed. Score should reflect what the patient does, 
not what the clinical thinks the patient can do. 
The Modified Rankin is a score that is given according to the scale provided below: 
0 = No symptoms at all 
1 = No significant disability despite symptoms; able to carry out all usual duties and activities 
2 = Slight disability; unable to carry out all previous activities, but able to look after own affairs 
without assistance 
3 = Moderate disability; requiring some help, but able to walk without assistance 
4 = Moderately severe disability; unable to walk without assistance and unable to attend to own 
bodily needs without assistance 
5 = Severe disability; bedridden, incontinent and requiring constant nursing care and attention 
6 = Dead 

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APPENDIX M: HOME DISCHARGE CHECKLIST 
 
 
Discharge Check List 
This checklist has been developed to be used as a guideline for the Discharge Criteria for each patient prior to 
going home. 
Acceptable 
Unacceptable 
Comments 
Stable Medical Condition. (e.g. 
Healing wounds, no sign if 
infection or sepsis) 
Acceptable Oxygen Saturation 
on room air 
Sinus Rhythm or Atrial 
arrhythmia with Ventricular 
rates < 120 bpm 
Able to walk 30 meters with 
Device without stopping due to 
shortness of breath, muscle 
fatigue, unsteady gait, pain 
Care–giver demonstrates 
aseptic technique in changing 
exit site dressing 
Patient and caregiver 
independently demonstrate 
connection and disconnection 
of the drivers 
Patient and caregiver 
independently demonstrate 
changing and recharging 
batteries 
Patient and caregiver 
understand and respond to the 
Driver Alerts and Alarms 
Home Assessment Visit prior to 
discharge 
All protocol required testing is 
completed up to point of 
discharge 
Patient Handbook supplied to 
patient, with Emergency 
Contact details specified 

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APPENDIX N: QUALITY OF LIFE QUESTIONNAIRES 
 
MINNESOTA LIVING WITH HEART FAILURE QUESTIONNAIRE 
 
This questionnaire is to be completed by the patient, after receiving basic instruction from the 
Clinical Investigator or Research Nurse (Instructor). All attempts should be made to administer 
the questionnaire: 
• by the same person each time, in same setting 
• before any other scheduled investigations or medical reviews 
• in isolation from spouse and/or other persons who might affect the answers 
Furthermore, the Instructor will not paraphrase the pertinent question if asked about the question, 
but just reiterate the pertinent instructions and the question itself, then ask the patient to respond 
according to what he or she thinks is appropriate 
Begin by showing the patient the questionnaire and asking that they answer a few questions. 
Tell the patient to read and think about each question carefully and telling them to make sure to 
answer all questions. Then go through the first question with him/her to make sure the 
instructions are clear – indicate that over the last month only. 
“If the answer is No then you circle the zero (point to zero). If the answer is Yes, then how much 
did it stop you living as you wanted over the last month – how much did it prevent you doing 
things, or how bothersome was it? 
Circling 1 means little effect, and circling 5 means very much effect. The 2–4 represent a range 
of effect in between little and very much. 

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Did your heart failure prevent you from living as you 
wanted during the last month by: 
No 
0 
Very Little 
1 
2 
3 
Very Much 
4 
5 
1. 
causing swelling of your ankles, legs, etc.? 
0 
1
2 
3 
4 
5 
2. 
making you sit or lie down to rest during the day? 
0 
1
2 
3 
4 
5 
3. 
making your walking about or climbing stairs difficult? 
0 
1
2 
3 
4 
5 
4.  making your working around the house or yard 
difficult? 
0 
1
2 
3 
4 
5 
5. 
making your going places away from home difficult? 
0 
1
2 
3 
4 
5 
6. 
making your sleeping well at night difficult? 
0 
1
2 
3 
4 
5 
7.  making your relating to or doing things with your 
friends and family difficult? 
0 
1
2 
3 
4 
5 
8. 
making your working to earn a living difficult? 
0 
1
2 
3 
4 
5 
9.  making your recreational pastimes, sports, or hobbies 
difficult? 
0 
1
2 
3 
4 
5 
10. making your sexual activities difficult? 
0 
1
2 
3 
4 
5 
11. making you eat less of the food you like? 
0 
1
2 
3 
4 
5 
12. making you short of breath? 
0 
1
2 
3 
4 
5 
13. making you tired, fatigued, or low in energy? 
0 
1
2 
3 
4 
5 
14. making you stay in a hospital? 
0 
1
2 
3 
4 
5 
15. costing you money for medical care? 
0 
1
2 
3 
4 
5 
16. giving you side–effects from medications? 
0 
1
2 
3 
4 
5 
17. making you feel you are a burden to your family or 
friends? 
0 
1
2 
3 
4 
5 
18. making you feel a loss of self–control in your life? 
0 
1
2 
3 
4 
5 
19. making you worry? 
0 
1
2 
3 
4 
5 
20. making it difficult for you to concentrate or remember 
things? 
0 
1
2 
3 
4 
5 
21. making you feel depressed? 
0 
1
2 
3 
4 
5 

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KANSAS CITY CARDIAC QUALITY OF LIFE QUESTIONNAIRE 
 
 
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1. Heart failure affects different people in different ways. Some feel shortness of breath while 
others feel fatigue. Please indicate how much you were limited by heart failure (shortness of 
breath or fatigue) in your ability to do the following activities over the past 2 weeks. 
Place an X in one box on each line. 
 
 
 
 
Dressing yourself 
Showering/Bathing 
Walking 1 block on ground 
level 
Doing yardwork, housework 
or carrying groceries 
Climbing a flight of stairs 
without stopping 
Hurrying or jogging (as if to 
catch a bus) 
Extremely 
Limited 
 
 
 
 
 
 
 
 
Quite a 
bit 
Limited 
 
 
 
 
 
 
 
Moderately 
Limited 
 
 
 
 
 
 
 
 
Slightly 
Limited 
 
 
 
 
 
 
 
 
Not at all 
Limited 
 
 
 
 
 
 
 
 
Limited for 
other 
reasons or 
did not do 
the activity 
 
 
 
 
 
 
 
 
 
 
 
2. Compared with 2 weeks ago, have your symptoms of heart failure (shortness of breath, 
fatigue or ankle swelling changed? 
My symptoms of heart failure have become: 
Much Worse 
Slightly worse 
Not Changed 
Slightly better 
Much better 
I’ve had no 
symptoms over 
the last 2 weeks 
 
3. Over the past 2 weeks, how many times did you have swelling in your feet, ankles or legs when you 
woke up in the morning? 
Every morning 
3 or more times a week, 
but not every day 
1-2 times a week 
Less than once a 
week 
Never over the past 2 
weeks 
 
 
 
 
 
 
 
4. Over the past 2 weeks, how much has swelling in your feet, ankles, or legs bothered you? 
It has been: 
Extremely 
bothersome 
Quite a bit 
bothersome 
Moderately 
bothersome 
Slightly 
bothersome 
Not at all 
bothersome 
I’ve had no swelling 
 
 
 
 
 
 
 

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5. Over the past 2 weeks, on average, how many times has fatigue limited your ability to do 
what you want? 
All of the time 
Several times 
per day 
At least once a 
day 
3 or more 
times per 
week but not 
every day 
1-2 times per 
week 
Less than once 
a week 
Never over the 
past 2 weeks 
 
 
 
 
 
 
 
 
 
6. Over the past 2 weeks, how much has your fatigue bothered you? 
It has been: 
Extremely 
bothersome 
Quite a bit 
bothersome 
Moderately 
bothersome 
Slightly 
bothersome 
Not at all 
bothersome 
I’ve had no fatigue 
 
 
 
 
 
 
 
 
7. Over the past 2 weeks, on average, how many times has shortness of breath limited your 
ability to do what you wanted? 
All of the time Several times 
per day 
At least once 
a day 
3 or more times 
per week but not 
every day 
1-2 times 
per week 
Less than 
once a week 
Never over the 
past 2 weeks 
 
 
 
 
 
 
 
 
 
8. Over the past 2 weeks, how much has your shortness of breath bothered you? 
It has been: 
Extremely 
bothersome 
Quite a bit 
bothersome 
Moderately 
bothersome 
Slightly 
bothersome 
Not at all 
bothersome 
I’ve had no 
shortness of breath 
 
 
 
 
 
 
 
 
9. Over the past 2 weeks, on average how many times have you been forced to sleep sitting up 
in a chair or with at least 3 pillows to prop you up because of shortness of breath? 
Every night 
3 or more times a week, 
but not every day 
1-2 times per week 
Less than once a 
week 
Never over the past 2 
weeks 
 
 
 
 
 
 
 
10. Heart failure symptoms can get worse for a number of reasons. How sure are you that you 
know what to do, or whom to call, if your heart failure gets worse? 
Not at all sure 
Not very sure 
Somewhat sure 
Mostly sure 
Completely sure 
 

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11. How well do you understand what things you are able to do to keep your heart failure 
symptoms from getting worse (for example, weighing yourself, eating a low salt diet, etc.)? 
Do not understand at all 
Do not understand 
very well 
Somewhat 
understand 
Mostly understand 
Completely 
understand 
 
 
 
 
 
 
 
12. Over the past 2 weeks how much has your heart failure limited your enjoyment of life? 
It has extremely limited 
my enjoyment of life 
It has limited my 
enjoyment of life 
quite a bit 
It has moderately 
limited my 
enjoyment of life 
It has slightly limited 
my enjoyment of life 
It has not limited my 
enjoyment of life 
 
 
 
 
 
 
 
13. If you had to spend the rest of your life with your heart failure the way it is right now, how 
would you feel about this? 
Not at all satisfied 
Mostly dissatisfied 
Somewhat satisfied 
Mostly satisfied 
Completely satisfied 
 
 
14. Over the past 2 weeks, how often have you felt discouraged or down in the dumps because 
of your heart failure? 
I felt that way all of the 
time 
I felt that way most 
of the time 
I occasionally felt 
that way 
I rarely felt that way 
I never felt that way 
 
 
 
 
 
 
 
How much does your heart failure affect your lifestyle? Please indicate how your heart failure 
may have limited your participation in the following activities over the past 2 weeks. 
Please place an X in one box on each line. 
 
Activity 
 
Hobbies, 
recreational 
activities 
Working or doing 
household chores 
Visiting family or 
friends out of your 
home 
Intimate 
relationships with 
loved ones 
 
 
Severely 
limited 
 
 
 
 
 
 
 
 
 
 
 
 
Limited 
quite a bit 
 
 
 
 
 
 
 
 
 
 
 
 
Moderately 
limited 
 
 
 
 
 
 
 
 
 
 
 
 
Slightly 
limited 
 
 
 
 
 
 
 
 
 
 
 
 
Did not 
limit at all 
 
 
 
 
 
 
 
 
 
 
Does not 
apply or did 
not do for 
other 
reasons 
 
 
 
 
 
 
 
 
 

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APPENDIX O: HEART FAILURE ASSESSMENTS 
 
NYHA Classification 
In 1928, the New York Heart Association published a classification of patients with cardiac 
disease based on clinical severity and prognosis. This classification has been updated in seven 
subsequent editions of Nomenclature and Criteria for Diagnosis of Diseases of the Heart and 
Great Vessels (Little, Brown & Co.). The ninth edition, revised by the Criteria Committee of the 
American Heart Association, New York City Affiliate, was released March 4, 1994. These 
classifications are summarized below. 
 
Class I. Patients with cardiac disease but without resulting limitation of physical activity. 
Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or angina. 
Class II. Patients with cardiac disease resulting in slight limitation of physical activity. They 
are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or 
angina. 
Class III. Patients with cardiac disease resulting in marked limitation of physical activity. They 
are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or 
angina. 
Class IV. Patients with cardiac disease resulting in inability to carry on any physical activity 
without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at 
rest. If any physical activity is undertaken, discomfort is increased. 
 
ACC/AHA Stages of Heart Failure 
In 2001, the ACC/AHA published an update subdividing clinical heart failure into four ‘stages’. 
The stages are listed below. 
 
Stage A. Patients at high risk for developing clinical HF (i.e. those with hypertension, diabetes, 
dyslipidaemia, and so on), but without detectable structural heart disease. 
Stage B. Patients with detectable structural heart disease (i.e. LVH, LV Dysfunction), but no 
clinical signs or symptoms of HF. 
Stage C. Patients with current or past clinical HF. 
Stage D. Patients with end-stage refractory HF, who are candidates for extraordinary forms of 
therapy or for compassionate end-of-life care. 

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APPENDIX P: SIX MINUTE HALL WALK 
 
The six minute walk test (6MWT) will be conducted as described by Guyatt et al.40 and as used 
by other investigators in heart failure clinical trials41 42. In a corridor, a 30.5 meter (100 feet) 
course (without elevations) will be marked and a chair will be placed at each end. The corridor 
should be long, flat, straight and one that is seldom travelled. The turnaround points should be 
marked with a cone (such as an orange traffic cone). A starting line, which marks the beginning 
and end of lap, should be marked on the floor using brightly colored tape. 
 
PATIENT PREPARATION 
• Comfortable clothing should be worn. 
• Appropriate shoes for walking should be worn. 
• Patients should use their usual walking aids during the test (cane, walker, etc.). 
• The patient's usual medical regimen should be continued. 
• A light meal is acceptable before early morning or early afternoon tests. 
• Patients should not have exercised vigorously within 2 hours of beginning the test. 
The patient should sit at rest in a chair, located near the starting position, for at least 10 minutes 
before the test starts. During this time, check for contraindications, measure pulse and blood 
pressure, and make sure that clothing and shoes are appropriate. 
Patients will be instructed to walk from end to end at their own pace while attempting to cover as 
much ground as possible in the allotted period of six minutes. A nurse coordinator will time the 
test, and encourage the patient every 30 seconds in a standardized fashion (while facing the 
patient and using one of two phrases: 
“You’re doing well” or “Keep up the good work”). Patients will be allowed to stop and rest 
during the test, but will be instructed to resume walking as soon as they feel they are able to do 
so. After six minutes, patients will be instructed to stop walking. The total distance walked will 
be measured to the nearest meter (and foot). Symptoms experienced by patients during the walk 
(e.g., angina, dyspnea, fatigue, dizziness) will be recorded. 
The six–minute walk test will be performed at baseline, 1, 3, 6, 12, 18 month, and annually 
thereafter through study closure. 
 
 
 
 
 
 
 
 
 
40 [Guyatt] 
41 [Bittner 1993] 
42 [Riley 1992] 

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Before the Baseline Six Minute Hall Walk test, a familiarization Six Minute Hall Walk test is 
required. The familiarization test should take place at least one hour before the Baseline test. If 
the patient had a test within 12 months of the Baseline test, that test will be considered a 
familiarization test. In addition, the Six Minute Hall Walk test should always be completed prior 
to the Cardiopulmonary testing with adequate time to rest before the CPX test (a minimum of 2 
hours is recommended). 

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APPENDIX Q: CARDIOPULMONARY EXERCISE TESTING 
OVERVIEW 
 
Cardiopulmonary exercise (CPX) testing will be performed at baseline and at the 6–month 
follow–up visit to assess patients’ exercise tolerance. 
Overview of Exercise Protocol for Cardiopulmonary Exercise Test 
CPX tests will be performed at baseline and 6 months. 
For all CPX tests, patients will be exercised until they have reached a symptom–limited 
maximal effort. Note: The patient should continue until he/she has reached a symptom– 
limited maximal effort or other American College of Sports Medicine (ACSM) reasons to 
discontinue testing occur.43 
Exercise will be performed on a treadmill using a modified Naughton protocol. Exercise 
will be initiated at 1 mph (miles per hour)/0% grade and the workload will be increased 
every two minutes to a symptomatic maximum (up to 3 mph/17.5% grade). 
Respiratory gases will be measured with a standard metabolic cart equipped with O2 and 
CO2 analyzers and a turbine volume transducer, which should be calibrated within 1 hour 
of testing. Continuous 12–lead ECG monitoring should be performed during the exercise 
test. The patient will then mount the treadmill and be exercised to his/her symptomatic 
maximum. Respiratory gas measurements will be made continuously while the patient 
exercises. Symptoms experienced by the patient during exercise (e.g., angina, dyspnea, 
fatigue, dizziness) will be recorded. Following a test, the patient should be observed for 
at least 15 minutes, or longer as determined by the investigator, before discharge from the 
laboratory. 
Baseline Testing Logistics 
At the beginning of the study, two CPX tests are required: 1) a “familiarization” test to 
allow the patient to become familiar with walking on a treadmill and with the breathing 
apparatus in his/her mouth, and 2) a baseline test. 
During the familiarization test, the patient should exercise to his/her symptomatic 
maximum. If the patient reaches his/her symptomatic maximum, this test may be 
considered the baseline test. The CPX Core Lab will assess the outcome of the test for 
acceptability as a baseline. 
The first test should be conducted pre-implant. If a second test is required, it should be 
conducted 48 hours after the first test and also pre–implant. When working the patient 
into the study and scheduling tests, plan for a 48 hour window between these tests. 
Note: If a patient has a documented CPX test that was performed within 6 months of the 
implant date, this test will be considered the familiarization test. However, the patient 
must still perform a baseline CPX test for the study, regardless of the previous CPX test. 
 
 
 
 
43 [Pollock 2000] 

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Measured Exercise Variables 
Minute oxygen consumption (VO2; ml/min), minute carbon dioxide production (VCO2; 
ml/min), and minute ventilation (VE; L/min) will be measured using a breath-by-breath 
respiratory gas analyzer. The RER will be calculated as VCO2/VO2. Minute oxygen 
consumption will be normalized for body size by dividing the patient’s weight in kg (VO2 
in ml/kg/min). Peak oxygen consumption will be that oxygen consumption at peak 
exercise with respiratory gas exchange ratio greater than 1.0. The oxygen consumption at 
anaerobic threshold will be determined by the V-slope method.44 This is the point during 
exercise at which the RER increases due to the generation of carbon dioxide. The 
anaerobic threshold divided by predicted maximum consumption for age and gender x 
100 will be calculated to assess for effort. The oxygen consumption divided by the 
predicted maximum x 100 will be calculated to normalize for age and gender. Watts and 
METS at peak exercise will be a measure of maximum workload, and exercise time will 
also be recorded. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
44 [Wasserman 1964] 

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APPENDIX R: STUDY SUMMARY 
 
 
TITLE 
C-Pulse® Implantable Counterpulsation Pump (ICP) US Feasibility Study 
A Heart Assist Device 
SPONSOR 
Sunshine Heart, Incorporated 
STUDY OBJECTIVES 
Assess the safety and provide indications of performance of the C-Pulse® device. The study 
will include 20 patients enrolled at up 7 centers in the US and potentially some OUS centers. 
The study will be expanded to include a total of 40 patients enrolled at up to 9 centers. Patient 
data will be collected at baseline, 1, 3, 6, 12, 18 months and annually to 10 years. 
BACKGROUND 
The current need is for a heart assist device or a method that is effective enough to make its 
application appealing as a long-term therapy to a large number of patients and physicians to 
treat patients in moderate to severe heart failure who are refractory to drugs. It must be simple 
and safe, with a straight-forward implant procedure, and with long-term measurable patient 
benefits. Further, it would be advantageous for the device to be small, easy to insert, 
disconnectable, not in the bloodstream and allows for patient ambulation. Such a device may 
be more readily adopted by a wider group of cardiologists and surgeons, and be suitable for a 
wider group of people in ACC/AHA Stage C, NHYA Class III/IV heart failure. 
Sunshine Heart, Inc. has proposed C-Pulse®, a novel ambulatory, non-obligatory, non-blood 
contacting extra-ascending aortic counterpulsation system. The C-Pulse® is designed to 
augment heart function in a safe manner and to provide sustained relief from heart failure 
symptoms. It can be turned off safely, and similarly, in failure modes, is considered to have an 
associated low risk of death or disability, other than the recurrence of heart failure symptoms. 
The C-Pulse® is not an alternative to the heart, it is an augmentation device, and it does not 
preclude the use of other heart failure therapies such as valve surgery, heart transplantation or 
LVADs. It is important to point out that a counterpulsation device is aimed to augment native 
heart function and is fundamentally different from total artificial hearts, left ventricular assist 
devices and heart transplants which are meant to be a total replacement or an alternative to the 
native heart. Thus, the C-Pulse® counterpulsation device is considered non-obligatory and not 
life-supporting. 
PURPOSE 
The purpose of the study is to determine whether use of the C-Pulse® used as treatment for 
patients in moderate to severe heart failure is associated with reasonable assurance of safety and 
performance, such that the C-Pulse® merits FDA approval for continuation into a pivotal study 
to examine the safety and efficacy of the C-Pulse® for US market approval. 

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DEVICE DESCRIPTION 
The C-Pulse® utilizes an “extra-aortic” inflatable Cuff which is surgically implanted around the 
ascending aorta. The C-Pulse® ICP has been designed to have a simple, highly reliable 
implantable component (the Cuff) and external wearable components (the Driver and Battery 
Carrier) which are connected by means of a Percutaneous Interface Lead. The Driver is 
programmable by a physician using a Programmer via infra-red (IR) connectivity. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The modular design of the C-Pulse® is shown the figure above. Key features are outlined in 
Table 1. For the IDE study, the patient will be provided with two (2) each of the Driver and 
Battery Carrier. The Percutaneous Interface Lead is designed to facilitate simple surgical 
replacement of the external component, in the case of skin infections at the exit site or damage 
to the patient connector. 
Table 1: C-Pulse® System Components 
SHC implantable Cuff: 
• 
Simple, less invasive surgery 
• 
No cardiopulmonary bypass 
• 
3 sizes to fit ascending aorta outside diameter 29 – 40 mm 
• 
Non-blood contacting 
SHC Percutaneous Interface Lead: 
• 
5 mm outside diameter 
• 
Silicone with ECG wire re-enforcements 
• 
Transmits air/ECG/heart sounds 
• 
Patient connector (with water-tight cap) 
• 
Lead is exchangeable 
• 
Home care package including supplies for dressing changes 
SHC wearable/portable Drive Unit and Battery Carrier system: 
• 
Detachable, approx. 2.5 kg (total weight, split between Driver and Battery Carrier) 
Ergonomic design 
• wear in a vest or carry in a bag 
• simple patient interface – on/off button and battery indicator 
• visual and audible alarms 
• 
4 hours battery life; single battery – recharge separately or in Battery Carrier 
• 
1.4m Driver cable with Isolation Module 
• 
Physician programmer 
• 
Infra-red functionality 
• 
Intuitive interface for setting counterpulsation functions 
• 
Discrete “verification” button on Driver to accept Programmer changes 

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SYSTEM 
DEFINITION 
Investigational Device: 
• 
C-Pulse® Cuff 
• 
Small Cuff 
• 
Medium Cuff 
• 
Large Cuff 
• 
Percutaneous Interface Lead 
• 
External Driver and Battery Carrier 
Accessories: 
• 
Battery Charger 
• 
Programmer 
• 
Vest 
• 
Carry bag 
• 
Home Care Kit (includes Percutaneous Lead Management Kit) 
• 
Epicardial bipolar IS-1 pacemaker lead; Capsure Epi 35 cm, (Medtronic, Inc., 
Minneapolis) 
PRIMARY 
OBJECTIVES 
The primary objective of the C-Pulse feasibility study is to assess safety, while at the same time obtain 
performance data for evidence of efficacy to assist planning for a pivotal study. Refer to the section on 
Statistical Methods and Data Analysis for a detailed discussion of the definitions and methodology. 
The Clinical Investigation shall: 
1. Assess the risks with regard to the performance of the device as defined by the serious adverse 
event rates, under normal conditions of use. 
2. Assess the potential benefits of C-Pulse as defined by improvements in Peak VO2, 
hemodynamic measures, quality of life and HF symptoms. 
SECONDARY 
OBJECTIVES 
Secondary objectives are intended to provide additional information on patient response and device 
performance and to allow planning for the pivotal study. The secondary objectives are as follows: 
1. Further assess the potential risks with regard to the performance of the device as defined by the 
device failure rate, adverse event rates, adverse event attribution, re-hospitalization rates, 
duration of support, and length of time to hospital discharge. 
2. Further assess the potential benefits of C-Pulse as defined by improvements in quality of life, 
fatigue impact scales, hemodynamics, average distance walked in the 6 minute hall walk test, 
and blood tests. 
3. Assess the device usage 

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STUDY DESIGN 
The study is designed to assess the safety and potential benefit of the C- Pulse™ System before 
initiating a wider randomized clinical trial to demonstrate efficacy. The effect of the C- Pulse™ system 
in relieving heart failure symptoms in patients with ACC/AHA Stage C; NYHA Class III – ambulatory 
Class IV heart failure will be documented with this study. 
This Feasibility Study is multi-center study in up to 7 centers in the US and potentially some OUS 
centers. The primary study population will include 20 subjects enrolled and implanted with the C- 
Pulse® System. The study will be expanded to include a total of 40 patients in up to 9 centers. The 
period of follow-up will be 6 months to assess the safety and performance before initiating the pivotal 
clinical trial. Patients will be followed for up to 5 years. 
Baseline 
Long term Follow-up 
Inclusion/Exclusion 
Implant 
1, 3, and 6 month 
12 and 18 month – 
Follow-up 
≤ 30 Days 
annually thereafter 
Figure 1.  Study Design 
Patients will be enrolled into the trial upon providing informed consent. Procedures related directly to 
the study must not be performed prior to informed consent. Data collection will be noted prior to 
implantation of the device and at one, three, and six months following implant and then annually post- 
implant for five years. Adverse events will be collected throughout the study until study closure and 
will be adjudicated by the CEC. 
Progress reports of the clinical outcomes will be prepared by the DSMB after enrollment of five (5) 
patients and twice per year thereafter, unless slow enrollment does not warrant this meeting frequency. 
Progression to the Pivotal study will be based on the assessment for safety of the device and indicators 
of performance. Baseline and follow–up data will be used to assess any significant difference in quality 
of life and functional variables pre and post implant and to assess the effect of counterpulsation. 
Following successful completion of this Feasibility Study, a pivotal study will be conducted to examine 
the safety and efficacy of the C-Pulse® system in patients in moderate to severe heart failure. The 
pivotal trial is expected to measure the same variables as the Feasibility Study. 
SUBJECTS- 
CENTERS- 
DURATION- 
Up to 40 eligible patients will be implanted with the C- Pulse® 
Up to 9 US Centers 
The total duration of the Feasibility Study is expected to be approximately - 120 months. 

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INCLUSION 
CRITERIA 
Patients of both genders who satisfy all inclusion and exclusion criteria are eligible for this clinical 
study. Patients must meet the following criteria: 
1. Patient has ACC/AHA Stage C heart failure and remains in NYHA Class III - ambulatory 
Class IV despite optimal medical therapy. Patients must have stable, evidence–based optimal 
medical therapy for heart failure as defined below: 
a. 
ACE inhibitor or ARB (Angiotensin Receptor Blocks) at least 30 days preceding 
implant or nitrate/hydralazine at the investigators discretion 
b. 
Beta–blocker for at least 90 days and stable for 30 days preceding implant 
Note: Stable is defined as no more than a 50% reduction or 100% increase in the medications 
listed above. Transition within a therapeutic class is allowed if the dose is equivalent 
2. Patient has left ventricular ejection fraction ≤ 35% 
3. Patient has had Cardiac Resynchronization Therapy (CRT) for at least 90 days prior to 
enrollment or is not indicated for a CRT device 
4. Patient has had an implanted cardio–defibrillator (ICD) at least 30 days prior to enrollment or 
is not indicated for ICD implantation 
5. Patient is at least 18 years of age and not older than 75 years 
6. Patient six minute hall walk assessment between 100–350 meters 
7. Patient understands the nature of the procedure, is willing to comply with associated follow–up 
evaluations, and provide written informed consent prior to the procedure 
EXCLUSION 
CRITERIA 
Candidates must be excluded from the study if any of the following are met: 
1. Patient has any evidence of : 
a ascending aortic calcification on posterior–anterior or lateral chest x–ray at initial screening OR 
b. Atherosclerotic ascending aortic disease, specifically intimal thickening greater than 3mm or 
mobile atheroma (moderate) or mural calcification (severe) as detected by CT scan or 
echocardiography 45 (Echo) 
2. Patient has ascending aorto-coronary artery bypass grafts, history of aortic dissection, Marfans 
disease or other connective tissue disorder or has had an aortic root replacement 
3. Patient aorta not conforming to specified dimensional constraints defined by CT scan, most 
specifically mid ascending aortic outside diameter less than 29mm or greater than 40mm 
4. Patient has severe mitral valve incompetence, grade 4 + 
5. Patient has moderate to severe aortic valve incompetence, grade 2–4+ 
6. Patient has systolic blood pressure less than 90 or greater than 140 mmHg 
7. Patient has a Serum Sodium less than 130 mEq/L 
8. Patient has a Estimated GFR less than 40 ml/min/1.73 m2 
9. Patient has any two of three of Bilirubin, AST, ALT greater than 3 times upper limit of normal 
for each institution 
 
 
45 [Davila–Roman 1999] 

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EXCLUSION 
CRITERIA 
(continued) 
10. Patient has a serum Albumin less than 3.0 g/dL 
11. Patient has BMI less than 18 or greater than 40 kg/m2 
12. Men with Peak VO2 of greater than 18ml/kg/min or less than 10 ml/kg/min 
13. Women with Peak VO2 of greater than 16 or less than 9 ml/kg/min 
14. Patient has any active infection 
15. Patient has had a myocardial infarction, stroke, transient ischemic attack, cardiac or other major 
surgery, in the 3 months prior to study enrollment. 
16. Patient has severe COPD as evidenced by FEV1 less than or equal to 0.9 L/min 
17. Patient requires a concomitant surgical procedure (i.e. CABG, Valve repair) 
18. Patient is supported with a left ventricular assist device or intra–aortic balloon pump. 
19. Severe right heart dysfunction with systemic venous congestion evidenced by clinical 
signs/symptoms such as CVP ≥ 20 mmHg , Cardiac Index < 2.0 l/min/m2, elevated liver 
function tests beyond three times the upper limit of normal with the presence of ascites. 
20. Patient has reversible causes of heart failure that may be remedied by conventional surgery or 
other intervention 
21. Patient is pregnant. Note: Negative pregnancy test required in all women of child bearing 
potential. 
22. Patient has any other condition that, in the opinion of the investigators, would disqualify the 
patient for inclusion in the study, limits survival to less than one year, or not permit valid 
consideration 
23. Patient is currently enrolled or has participated in the last 30 days in another therapeutic or 
interventional clinical study that is likely to confound study results or affect study outcome 
24. Patient has symptomatic Carotid artery disease or asymptomatic disease with a stenosis greater 
than 70% as determined by Carotid Doppler Ultrasound. 
 
Data Collection Summary 
 
 
Follow-up Requirements Baseline to 6 months Post Implant 
Pre-Implant 
Implant 
Pre-Discharge7 
1 mo 
3 mo 
6 mo 
A. PATIENT ELIGIBILITY 
X 
B. GENERAL 
Demographic Data 
X 
Medical History 
X 
General Physical Examination 
X 
X 
X 
X 
X 
X 
Concurrent Medications 
X 
X 
X 
X 
X 
X 
Pregnancy test (if applicable) 
X 
C. VITAL PARAMETERS 
Weight 
X 
X 
X 
X 
X 
Heart rate 
(ECG pre-implant) 
X 
X 
X 
X 
X 
Blood pressure 
X 
X 
X 
X 
X 

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Follow-up Requirements Baseline to 6 months Post Implant 
Pre-Implant 
Implant 
Pre-Discharge7 
1 mo 
3 mo 
6 mo 
Respiratory rate 
X 
X 
X 
X 
X 
D. CARDIOPULMONARY 
CT aorta 
X 
X 
CXR 
X 
X 
X 
ECHO 
X 
X2 
X 
X 
X 
Right heart catheterization 
(CVP, PAP, CI, PCWP, SVR, PVR) 
X 
X 
Peak O2 uptake 
X 
X 
E. QUALITY OF LIFE 
NYHA Classification 
X 
X 
X 
X 
MLHF Score/ KCCQ 
X 
X 
X 
X 
Fatigue Impact Scales 
X 
X 
X 
X 
X 
Six Minute Walk 
X 
X 
X 
X 
F. HEMATOLOGY 
Hemoglobin 
X 
X 
X 
X 
X 
Hematocrit 
X 
X 
X 
X 
X 
Plasma free hemoglobin 
X 
X 
X 
X 
X 
Platelet count 
X 
X 
X 
X 
X 
White cell count 
X 
X 
X 
X 
X 
APTT 
X 
X 
X 
X 
X 
INR 
X 
X 
X 
X 
X 
Fibrinogen 
X 
X 
X 
X 
X 
G. BIOCHEMISTRY 
Serum sodium 
X 
X 
X 
X 
X 
Serum potassium 
X 
X 
X 
X 
X 
Serum creatinine/ GFR3 
X 
X 
X 
X 
X 
BUN 
X 
X 
X 
X 
X 
Serum albumin 
X 
X 
X 
X 
X 
Serum bilirubin 
X 
X 
X 
X 
X 
Serum ALT 
X 
X 
X 
X 
X 
Serum AST 
X 
X 
X 
X 
X 
Serum BNP 
X 
X 
H. NEUROLOGICAL ASSESSMENT6 
Neurological testing (NIHSS)4 
X 
X 
X 
X 
X 
Modified Rankin 4 
X 
X 
X 
X 
X 
Head CT 5 
X 
Neurological Consultation 
X 
X6 
I. IMPLANT DETAILS 
X 
J. DEVICE LOG 
X 
X 
X 
X 
K. DISCHARGE CHECKLIST 
X 
1 Annually post-implant 
2 Epi-aortic Echo at implant 
3 Estimated GFR at Baseline and within one week post CT to evaluate contrast induced nephropathy. 
4 Post Neurological Dysfunction AE – 30, 60 and 90 days post event 
5 At Baseline only or as clinically indicated with any Neurological Dysfunction AE – Head CT should be completed only after clearance 
for implantation. 
6 Required at 5-7 days post ICU discharge or at hospital discharge whichever occurs first and at the time of any suspected Neuro 
Dysfunction AE 
7 At Discharge – within 36 hours prior to discharge and as close to discharge as possible (see Appendix M) 

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Long-term Post Implant Follow-Up Requirements 
12 month 
18 month 
Annually 
Year 2-10 
A. PATIENT ELIGIBILITY 
B. GENERAL 
General Physical Examination 
X 
X 
X 
Concurrent Medications 
X 
X 
X 
Pregnancy test (if applicable) 
C. VITAL PARAMETERS 
Weight 
X 
X 
X 
Heart rate 
(ECG pre-implant) 
X 
X 
X 
Blood pressure 
X 
X 
X 
Respiratory rate 
X 
X 
X 
D. CARDIOPULMONARY 
ECHO 
X 
X 
X 
E. QUALITY OF LIFE 
NYHA Classification 
X 
X 
X 
MLHF Score/ KCCQ 
X 
X 
X 
Fatigue Impact Scales 
X 
X 
X 
Six Minute Walk 
X 
X 
X 
F. HEMATOLOGY 
Hemoglobin 
X 
X 
X 
Hematocrit 
X 
X 
X 
Plasma free hemoglobin 
X 
X 
X 
Platelet count 
X 
X 
X 
White cell count 
X 
X 
X 
APTT 
X 
X 
X 
INR 
X 
X 
X 
Fibrinogen 
X 
X 
X 
G. BIOCHEMISTRY 
Serum sodium 
X 
X 
X 
Serum potassium 
X 
X 
X 
Serum creatinine/ GFR3 
X 
X 
X 
BUN 
X 
X 
X 
Serum albumin 
X 
X 
X 
Serum bilirubin 
X 
X 
X 
Serum ALT 
X 
X 
X 
Serum AST 
X 
X 
X 
I. IMPLANT DETAILS 
J. DEVICE LOG 
X 
X 
X 
K. DISCHARGE CHECKLIST7 

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APPENDIX S: BIBLIOGRAPHY 
 
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Clavell AL, Hayes DL, Ellestad M, and Messenger J for the MIRACLE Study Group. 
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Ash, SR. Chronic peritoneal dialysis catheters: effects of catheter design, materials and location. 
Seminars in Dialysis 1990;3:39–46. 3. 
Barnett MG, Fiore AC, Vaca KJ, Milligan TW, Barner HB. Tailoring aortoplasty for repair of 
fusiform ascending aortic aneurysms. Ann Thorac Surg 1995;59:497–501 
Bauer M, Grauhan O, Hetzer R.Dislocated wrap after previous reduction aortoplasty causes 
erosion of the ascending aorta. Ann Thorac Surg. 2003;75:583-4 
Bittner V, Weiner DH, Yusuf S, et al. “Prediction Of Mortality And Morbidity With A 6–Minute 
Walk Test In Patients With Left Ventricular Dysfunction”. JAMA 1993; 270:1702–1707 
Carel T, von Segesser L, Jenni R, et al. Dealing with dilated ascending aorta during aortic valve 
replacement: advantages of a conservative surgical approach. Eur J Cardiothorac Surg 
1991;5:137–43 
Cheung AT, Savino JS, Weiss SJ. Beat–to–beat augmentation of left ventricular function by 
intraaortic counterpulsation. Anesthesiology 1996;84:545–54. 
Cochran RP, Starkey TD, Panos AL, et al. Ambulatory intraaortic balloon pump use as bridge to 
heart transplant. Ann Thorac Surg 2002;74:746–52. 
Cohen M, Patel JJ, Dohad S, McBride R, Venkatesulu S, Boston BA, Chandrasekaran K. Pilot 
prospective evaluation of counterpulsation with different intra–aortic balloon volumes on 
cardiac performance in humans.Cathet Cardiovasc Diagn. 1995;36:82–7 
Davies AN, Peters WS, Su T, Sullivan CE, Perkidides T, Milsom FP, White G. Extra–ascending 
aortic versus intra–descending aortic balloon counterpulsation – effect on coronary artery 
blood flow. Heart, Lung & Circulation 2004. In press 
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Gitter R, Cate CM, Smart K, Jett GK.Influence of ascending versus descending balloon 
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Jeevanandam V, Jayakar D, Anderson AS, Martin S, Piccione W Jr, Heroux AL, Wynne J, 
Stephenson LW, Hsu J, Freed PS, Kantrowitz A. Circulatory assistance with a permanent 
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Riley M, McParland J, Stanford CF, Nicholls DP. “Oxygen Consumption During Corridor Walk 
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APPENDIX T: CLINICAL STUDY AGREEMENT TEMPLATE 
 
Not related to this change – not resubmitted 

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APPENDIX U: INFECTION CONTROL GUIDELINES 
 
Overview 
Infection control encompasses many factors including nutrition, management of conditions such 
as diabetes, prophylactic treatments and exit site care. 
Prior to surgery it is recommended that the nutritional status of the patient be assessed and 
addressed if the status is marginal. In addition, controlling blood sugar levels in the diabetic 
patients is also important. 
Pre-Operative Recommendations: 
• 
Nutritional status of the patient should be assessed prior to surgery. If nutritional status 
of the patient is marginal, attempts should be made to improve the patient’s nutritional 
status prior to surgery. 
• 
Diabetic patient’s glucose levels should be normalized on a stabile regimen prior to 
surgery. 
• Percutaneous Interface Lead (PIL) exit site should be pre-selected and marked prior to 
surgery. Pre-select an exit site for the Percutaneous Interface Lead that will facilitate PIL 
immobilization as well as patient selection for clothing, daily routine, etc. This should 
preferably be done while the patient is standing. Pre-selection of the PIL exit site will 
help to facilitate effective PIL immobilization after implant. Pre-selection at the very 
least should take into account patient body habitus, patient’s dominant hand, as well as 
input from the patient concerning daily routine and fit of clothing. 
 
Prep for surgery: 
Pre-select an exit site for the Percutaneous Interface Lead that will facilitate the patient selection 
for clothing, daily routine, etc. 
Prepare and shave the patient: Pre-operative scrub with antiseptic (Septisol or Chlorhexidine) on 
the night prior to surgery then again the morning of the surgery, and clip and shave the surgical 
area prior to transport to the operating room. 
Antibiotic prophylaxis recommendations: 
Administer prophylactic antisepsis coverage. Recommended prophylaxis: 
• Nasal Bactroban application day prior to surgery 
• Vancomycin 15mg/kg IV one hour pre–op given over 30 minutes and with minimum 5 
minute interval blood pressure monitoring or arterial line monitoring – note that 
Vancomycin can cause hypotension in this patient population and should not be given 
unsupervised pre-operatively on the ward. Follow-up doses Q12–24 hr post-operatively 
for 48 hrs, guided by serum Vancomycin trough levels 
• Cephalexin 1g IV one hour pre–op then every 8–12hr for 48 hrs 
• Rifampicin 600 mg PO 2hrs pre–op then daily for 2 days – stop if liver function tests 
become deranged greater than two times baseline 

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Peri-operative recommendations: 
• Observe Operating Room precautions – particularly, limit the number of people in the 
room, and traffic in and out of the room. 
• Recommend approach to skin preparation: 
o antiseptic scrub (Septisol or Chlorhexidine) 
• Drape patient with steri-drapes (e.g. Ioban), over exposed prepared skin. 
• Delay opening of the C-Pulse until necessary. Massage with antibiotic prior to 
implantation. 
• Massage flocking and wrap with antibiotic soaked gauze (e.g. standard mix doxycycline) 
prior to implantation. Keep the C-Pulse devices and driveline covered with antibiotic 
gauze while on OR prep table. 
• The PIL should be inserted in such a manner that the flocking is not visible at the end of 
surgery. 
• After implantation and before leaving the OR, close the exit site for good apposition and 
leave sutures in place for 7-10 days. Place a suture-tie on the PIL adjacent but separate 
(1-2 cm) from the exit site and leave in place for 4-6 weeks. Secure the Percutaneous 
Interface Lead (PIL) Patient Connector and the Driver Lead connector with two points of 
anchor using two separate adhesive catheter securement devices. Strict immobilization of 
the PIL at the skin exit site is crucial to getting effective flocking anchoring by fibrosis 
formation and preventing infection at the PIL exit site. 
Post-Implantation Recommendations: 
• Chest and other drains should be removed as soon as practical, at the discretion of the 
surgeon, and typically within 48 hours, depending on drainage. 
• Monitor patient’s nutritional status and intervene early if their status becomes marginal. 
• An Insulin infusion should be established in patients with diabetes or other glucose 
intolerance until a regular diet and normal diabetic therapy can be re-introduced. Early 
mobilization and graduated physical therapy should be conducted as tolerated from day 1. 
The Carry Bag Waist Strap and Driver Lead coiling Velcro strap should be used when 
ambulating. Ambulation should be started gradually and used with assistance from 
physical therapy or other hospital staff. 
• The C-Pulse Driver Lead should be attached to the patient’s clothing or 
secured with the coiling strap to establish a 3rd level of stress relief for the 
driveline while the patient is out of bed. 
• PIL dressing changes should be performed strictly following dressing change protocol 
and should be limited to as few people as possible. Ongoing oral broad spectrum/gram 
negative antibiotics are recommended for or until chest drains are removed and the exit- 
site has dried sufficient for once daily dressing only. 

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• Provide ongoing education to patient and caregivers on general hygiene, e.g. regular hand 
washing and importance of PIL immobilization and care, to avoid pulling to treat 
percutaneous line gently and to avoid undue pulling, pushing or torque at the PIL exit 
site. 
• Schedule removal of the skin suture tie at the PIL exit site according to the physician 
orders. 
.Exit Site Care: 
PIL Exit Site Dressing Change Key Points 
• Exit site dressing and lead stabilization should occur in the OR prior to the patient 
transferring from the OR table. 
• First 72 hours post-implant – dressing should remain unchanged as long as it remains 
dry.be changed as frequently as required post–operatively whilst ensuring that the 
percutaneous lead is immobilized.– this may be up to 2–3 times per day in the first 1–2 
weeks if it is oozing. If wounds are healing well and there is no discharge, then go to 
daily or second-daily dry dressings. 
• If the dressing becomes soiled, it should be changed immediately 
• As post-operative drainage decreases, exit site dressing changes can be decreased to once 
daily or once every other day. 
• Strict immobilization of the PIL site should be observed at all times. The PIL patient 
connector and driver lead connector should be stabilized using two adhesive catheter 
securement devices - one for the PIL patient connector and one for the driver lead. 
• The Driver should remain in the Carry Bag at all times when being used by the patient, 
Careful attention should be made to prevent the Driver from falling or being dropped. 
• Limitation of personnel around patient should be exercised while performing PIL exit site 
dressing changes to limit contamination of PIL exit site. 
• Patient and/or Caregiver should be taught strict dressing change procedure and allowed to 
take over dressing changes as soon as they are competent. 
 
Dressing Change Procedure 
The following procedure is to be followed for all PIL exit site dressing changes. 
Equipment needed: 
• 
Driveline Management Kit 
• 
One adhesive catheter securement device (in addition to that supplied in the driveline 
management kit). 
OR: 
• Masks (2) 

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• Disposable sterile drape or towel (1) 
• Clean gloves (1 pair) 
• Sterile gloves (1 pair plus one unopened pair for backup) 
• 2 Chlorhexidine surgical prep swab sticks (2% Chlorhexidine) or 2% Chlorhexidine 
Solution 
• 4X4 drain sponge (1 packet of 2 sponges) 
• 4X4 gauze pad (1 packet of 2 pads) 
• Clear occlusive Dressing (i.e. Tegaderm) 
• 2 adhesive catheter securement devices (i.e. a catheter anchor for the PIL patient 
connector and the Driver Lead) 
Procedure Using Driveline Management Kit: 
1. Wash hands and arms thoroughly with water and antibacterial soap. Dry using a clean 
disposable towel. 
2. Place a mask over the nose and mouth of everyone in the room, including the patient if 
possible. 
3. Put on clean gloves. 
4. Open the dressing kit using sterile technique. 
5. Remove open the sterile towel to create a sterile field. 
6. Open and drop the chlorohexadine swab sticks into the driveline management kit 
container. Open and drop the 4X4 gauze pad and drain sponge on the sterile field. 
7. Remove and discard old dressing. 
8. Examine the site for problems with PIL integrity and signs of infection (e.g. purulent 
drainage, redness or tenderness to palpation). 
9. If signs of infection are present, culture exit site drainage using a sterile culturette. 
10. Examine the adhesive catheter securement devices. Remove if adhesive is coming loose 
or if PIL immobilization requires revision. Be sure to allow as little movement as 
possible of the PIL at the exit site. 
11. Remove dirty gloves and don sterile gloves. This must be done observing strict sterile 
technique. 
Note: It may be helpful to have another set of sterile gloves immediately available in the 
event contamination occurs. 
12. Clean the PIL exit site and the percutaneous lead with the Chlorahexadine swab sticks. 
a.  Follow a circular pathway from the catheter outward. Use gentle pressure moving 
from the exit site outward. 
b. Discard each swab once lifted from the patient's skin. 

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13. Allow solution to air dry for at least 2 minutes. DO NOT DRY THE SITE WITH A 4x4. 
14. Take a picture and upload it to the electronic data capture system 
15. Apply the 4x4 drain sponge and the SorbaView Shield Dressing 
16. If not using Centurion supplies, apply a large clear occlusive dressing, or tape 
reinforcement to entire site covering the drain sponge and PIL. 
17. Ensure that the PIL is immobilized without twisting or tension by the two separate 
adhesive catheter securement devices at two separate locations, one at the PIL patient 
connector and one at the driver lead connector. If either anchor is compromised replace it 
immediately. 
Procedure Without Driveline Management Kit: 
1. Wash hands and arms thoroughly with water and antibacterial soap. Dry using a clean 
disposable towel. 
2. Place a mask over the nose and mouth of everyone in the room, including the patient if 
possible. 
3. Put on clean gloves. 
4. Open the disposable sterile towel to create a sterile field. 
5. Open the 4x4 gauze pads and 4x4 drain sponges and drop them on the sterile field. 
6. Pour the Chlorhexidine cleansing solution (2%) onto the gauze pad or drop the 
chlorhexadine swab sticks onto the sterile field. 
7. Remove and discard old dressing. 
8. Examine the site for problems with PIL integrity and signs of infection (e.g. purulent 
drainage, redness or tenderness to palpation). 
9. If signs of infection are present, culture exit site drainage using sterile culturette. 
10. Examine the adhesive catheter securement devices. Remove if adhesive is coming loose 
or if PIL immobilization requires revision. Be sure to allow as little movement as 
possible of the PIL at the exit site. 
11. Remove dirty gloves and don sterile gloves. This must be done observing strict sterile 
technique. 
Note: It may be helpful to have another set of sterile gloves immediately available in the 
event contamination occurs. 
12. Clean the PIL exit site and the percutaneous lead with the Chlorhexidine soaked gauze or 
swabs. 
a. 
Follow a circular pathway from the catheter outward. 
a. Discard each gauze pad or swab once lifted from the patient's skin. 
b. If using Chlorhexidine solution on 4x4 gauze pads allow one pad to remain 
wrapped around PIL for 2 minutes then remove and discard 
13. Allow solution to air dry for at least 2 minutes. DO NOT DRY THE SITE WITH A 4x4. 

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14. Take a picture and upload it to the electronic data capture system 
15. Apply a 4X4 drain sponge around the PIL. 
16. Apply large clear occlusive dressing (i.e. Tegaderm) or tape reinforcement to entire site 
covering the drain sponge and PIL. 
17. Ensure that PIL is held immobile without twisting or tension by the adhesive catheter 
securement devices at two separate locations, one at the PIL patient connector and one at 
the driver lead connector. If either anchor is compromised replace it immediately. 
Additional Comments: 
- 
No ointment or cream should be use at any time on the percutaneous lead of the C-Pulse 
unless directed to do so by the surgeon (no other physician). 
- 
Inspect the Driver Carry Bag to be sure the integrity of the Velcro strap used to coil the 
Driver Lead. 
- 
Take digital photos of the exit site to document the condition for future reference. 
Infection Advisory Committee Recommendations: 
Due to the possible interaction of site infection leading to “Deep” infection or tissue swelling 
around the intrathoracic gas line and /or ascending aorta an infection procedure monitoring 
process is recommended. The following process is recommended to reduce risk of injury to the 
patient. 
Infection Monitoring Process: 
In the presence of clinical signs (pain, redness, discharge, loss of driveline fixation) and /or 
microbiological evidence (positive wound culture) of infection (intermittent or chronic) over a 3 
month period despite treatment. 
Decision Process: 
Are there clinical signs or microbiological evidence of infection over a 3 month period despite 
treatment? 
• No: Continue therapy 
• Yes: Perform CT or PET scan 
- 
If scan is positive (i.e. shows evidence of DEEP infection or soft tissue swelling around 
the intrathoracic gas line and/or ascending aorta or presence of intrathoracic gas), then 
REMOVE PIL AND CUFF. 
- 
If scan is negative (i.e. shows no evidence of DEEP infection), REMOVE PIL only. 
- 
If at the time of surgery there is clinical evidence of DEEP infection (i.e. pus or fluid 
around the ‘Y’- connector, positive gram stain, and infected tissue) then REMOVE the 
CUFF also. 
• If at the time of CT/PET scan or surgery there is no evidence of DEEP infection, then 
REPEAT SCAN at 3 months post-op and monitor for clinical signs of infection, if none 
found then REPEAT SCAN annually. 
• NOTE: If wound culture is positive for MRSA, MSSA or Pseudomonas, monitor more 
frequently with FOLLOW-UP CT-SCAN at 3 months. 

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Aortic Tissue Sampling Guideline 
In the event of a heart transplant, LVAD or patient death it is recommended that the C-Pulse 
system be removed. To ensure evaluation of the system and patient interaction the following 
process provides guidance on removal of the C-Pulse implanted components at the time of 
explant, the observations to be recorded and for device return for analysis. 
• If possible, return the devices intact and connected. In the event of device dissection, 
attempt to maintain the connections intact. 
• For the Cuff, balloon integrity should be maintained unless histopathological analysis 
requires dissection. 
• Depending upon the event (a heart transplant, LVAD or patient death) the following 
three tissue samples of the aorta should be collected for analysis from patients 
implanted with the C-Pulse system: 
- 
under the cuff/balloon 
- 
proximal to the C-Pulse Cuff 
- 
distal to the C-Pulse Cuff 
- 
For control arm patient one tissue sample for the ascending aorta should be 
collected for analysis 
• The aorta samples should be sent to the local pathology lab for hematoxylin and eosin 
stain histological studies. Microbial analysis should be undertaken at the time of 
explant. 
• Cultures should be obtained at the skin exit site, at the y-connector of the PIL and at the 
balloon cuff and processed at the local laboratory for assessment of organisms. 

PRO 02291–I Protocol C–Pulse Investigational Plan 
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APPENDIX V: INVESTIGATIONAL PLAN REVISIONS 
 
The protocol amendments are listed below along with the justifications for change and the 
associated dates of the protocol revisions. Version 1 (PRO 02291-A) was sent to IRBs for study 
preparation. 
 
Version 1 
Justification for Change 
Page(s) 
Initial Version– Date 7 June 
2007 
Submission for IDE 
All 
 
Version 2 (PRO 02291-B) was created in response to FDA questions and incorporates the 
changes below. It was not delivered to IRBs for preparation of study documents. 
 
Version 1 
Version 2 
Justification for Change 
Page(s) 
Randomized study 
design, 24 pts., 
blinded study. 
Non-randomized study design, 20 
pts. Removed all references to old 
design and corrected study design. 
To address FDA concern. 
7, 15-16, 21-27, 54- 
55, 108-9 
Previous study 
population and 
eligibility criteria. 
Updated eligibility criteria and 
associated references. 
To address FDA concern. 
15, 17-19 
NA 
Added additional screening process. 
To address FDA concern. 
20-21 
NA 
Clarification and addition of 
required testing with associated data 
collection intervals. 
To address FDA concern. 
23-27,29, 93 
NA 
Clarification and addition of 
infection control guidelines. 
To address FDA concern. 
31-32, 119-121 
NA 
Adverse events – clarified use of the 
Intermacs registry definitions. 
Rearranged AE section for 
clarification. 
To address FDA concern. 
34-41 
Previous study 
design. 
Replaced Stat Section with updated 
analysis. 
To address FDA concern. 
42-44 
HF Composite 
Removed the HF Composite due to 
removing randomization and to us 
individual assessment analysis in the 
feasibility. 
To address FDA concern. 
54 
DSMB and CEC 
paragraphs. 
Relocated these paragraphs into the 
study safety section. 
Clarification. 
59-60 
Device usage 
statements 
Clarified the usage to be greater than 
80% of the time. 
To address FDA concern. 
13,31 
NA 
Added Core Lab information sheet. 
To address FDA concern. 
94 
Study Summary 
Updated with all relevant main 
protocol changes. 
Clarification. 
108-114 
NA 
Typos corrected. 
Administrative 
Throughout. 

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Version 3 (PRO 02291-C) was created in response to FDA questions and incorporates the 
changes below. 
 
Version 2 
Version 3 
Justification for Change 
Page(s) 
Device usage 
statements 
Deactivation time for the device 
limited to 15 minute intervals with a 
maximum acceptable 30 minute 
interval. 
To address FDA concern. 
13, 15, 32, 84 
Previous study 
population and 
eligibility criteria. 
Updated eligibility criteria with 
expanded definition of right heart 
failure. 
Modified Peak VO2 to be better 
suited for inclusion of women. 
To address FDA concern. 
18 
NA 
Expanded the neurological 
assessment data collection. 
To address FDA concern. 
26-27, 85 
NA 
Added Fatigue Impact Scales to the 
data collection and to case report 
forms. 
To address FDA concern. 
23, 27, 45, 83, 85, 
86, Appendix K 
NA 
Adverse events – clarified 
unanticipated device effect (UADE) 
definition. 
Clarification 
41 
NA 
Typos and grammar correction. 
Updated names of CRF titles. 
Administrative 
Throughout 
NA 
Changes listed above incorporated 
into Study Summary. 
Administrative 
Appendix R 
 
Version 4 (PRO 02291-D) was created in response to FDA questions and incorporates the 
changes below. 
 
Version 3 
Version 4 
Justification for Change 
Page(s) 
Investigator 
Signature Page 
Deleted this page. All Principle and 
Sub Investigators sign the Clinical 
Study Agreement that includes 
language requiring them to follow 
the protocol and GCP, etc. 
Clarification 
Formerly pg. 6 
Eligibility Criteria 
Changed Albumin Exclusion level 
from 3.5 to 3.0 g/dL and changed 
upper BMI limit from 38 to 40. 
Clarified the clinical study exclusion 
to include studies that would 
confound the results of the C-Pulse 
study. 
Investigator input from our 
last Investigator Meeting – 
the feedback indicated that 
the patient population for 
Class III would include 
patients with lower 
Albumin and larger BMI. 
18 
Investigational 
Center Information 
Section 
Added that sites will send in lab 
normals for our clinical study files to 
help ensure all labs are collected 
within comparable normal limits. 
Clarification 
22 

PRO 02291–I Protocol C–Pulse Investigational Plan 
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Version 3 
Version 4 
Justification for Change 
Page(s) 
Data Collection 
Summary Section 
Expanded CT Scan language to 
include suggestions for minimizing 
renal insult due to the use of 
contrast. 
Included requirement to perform 
Head CT only after the patient is 
determined eligible for implantation. 
To address FDA concern. 
23 
Data Collection 
Overview Section 
Expanded Neurological Assessment 
to include the Modified Rankin. 
Refine the section for clarity of 
neuro assessment requirements. 
To address FDA concern. 
23 
Data Collection 
Overview Section 
Added Six Minute Hall Walk at 1 
month timeframe to correspond with 
the NYHA and QoL assessments. 
Additional data for 1 
month interval. 
23 
Hospital Discharge 
Section 
Additional language added for 
clarification of data collection if 
readmitted and for discharge. 
Clarification 
36 
AE Section 
Added definition of serious. 
Removed reference to children 
under 6 months from Neuro AE. 
Added Modified Rankin for data 
collection following Neuro AE. 
Clarification 
37 
Explant Handling 
Section 
Added additional instruction. 
Clarification 
44 
Statistical Methods 
Section 
Changed Peak VO2 and Six Minute 
Hall Walk values to 1.2 ml/kg/min 
and 50 m, respectively. 
To address FDA concern. 
46 
Sample Informed 
Consent 
Changes listed above incorporated 
into the sample informed consent as 
appropriate. 
Administrative 
82 
Appendices 
Added the KCCQ, Modified Rankin 
and ACC/AHA Stages. 
Administrative 
100, 105, 110 
Appendix C 
Updated Investigator for UAB . 
Administrative 
74 
Appendix K 
Refined Sample Case Report Forms 
to incorporated changes listed 
above. 
Administrative 
99 
Appendix R 
Changes listed above incorporated 
into Study Summary. 
Administrative 
114 
NA 
Typos and grammar correction. 
Administrative 
Throughout 

PRO 02291–I Protocol C–Pulse Investigational Plan 
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Version 5 (PRO 02291-E) was created in response to FDA questions and incorporates the 
changes below. This was sent to sites for IRB submission along with the Conditional FDA 
approval letter dated 10 Sept 2008. 
 
Version 4 
Version 5 
Justification for Change 
Page(s) 
NA 
Addition of data requirement to 
monitor contrast induced 
nephropathy. 
FDA Request #1 - 
Conditional Letter from 10 
Sept 2008 
24, 27, 41, 
Appendix H – 
Informed Consent 
Indications for Use 
Removed sentence stating “The C– 
Pulse® System is a therapy indicated 
for patients who can tolerate 
intermittent use.” 
FDA Request #2 - 
Conditional Letter from 10 
Sept 2008 
12 
Appendix K 
Modified the Enrollment Case 
Report Form to include the 
alternative therapy a patient could 
receive if C-Pulse wasn’t available. 
FDA Request #3 – 
Conditional Letter from 10 
Sept 2008 
Appendix K – 
Enrollment Form 
Study Size and 
Duration section 
All subjects must be consented prior 
to performing any study related 
procedures. A subject is considered 
enrolled upon signing the informed 
consent. To minimize the burden to 
the patient, data collected as 
standard of care and not for the 
specific reason for study eligibility 
may be used for the baseline data 
points as outlined in the informed 
consent. These tests will suffice for 
the respective portion of the baseline 
dataset if collected within the pre- 
implant evaluation timeframe of 30 
days prior to implant. 
FDA Request #4a – 
Conditional Letter from 10 
Sept 2008 
6, 21 
Study Size and 
Duration section and 
Appendix K 
Study Exit instruction included as 
follows: Study Exit of these patients 
must be documented on the study 
exit form. The study exit form 
contains information on reason for 
study exit. Study Exit form 
modified to include details. 
FDA Request #4b – 
Conditional Letter from 10 
Sept 2008 
21, 22, 30, 43 
Appendix K – 
study exit form 
Design section and 
Screening and 
Patient Informed 
section 
Any patient whom undergoes 
anesthesia for the purpose of C- 
Pulse implantation but does not 
receive the device will be monitored 
for adverse events as defined by the 
protocol for 30 days or discharge 
whichever occurs first. 
FDA Request #4c – 
Conditional Letter from 10 
Sept 2008 
14, 21 
Screening and 
Patient Informed 
Consent section 
A Screening Log is located in the 
site Regulatory Binder and must be 
completed for all patients screened 
for eligibility. 
FDA Request #5 – 
Conditional Letter from 10 
Sept 2008 
21 

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Version 4 
Version 5 
Justification for Change 
Page(s) 
NA 
Additional data collection added to 
assess if a patient is required to use 
the C-Pulse due to symptoms during 
the time that they could be 
disconnected if symptoms were not 
present. 
FDA Request #6 – 
Conditional Letter from 10 
Sept 2008 
Appendix K – 
follow-up form 
Data Collection 
Overview section 
and Informed 
Consent (Appendix 
18 month follow-up visit added. 
FDA Request #7 – 
Conditional Letter from 10 
Sept 2008 
14,22,24-30, 
46,88,96,117,121 
Secondary 
Objectives 
Added analysis of Concomitant 
Medications from baseline to 6 
months. 
FDA Request #8 – 
Conditional Letter from 10 
Sept 2008 
46 
Exclusion Criteria 
Changed mild to moderate for aortic 
valve incompetence – Exclusion 
Criteria #5. 
FDA Request #9 – 
Conditional Letter from 10 
Sept 2008 
18, 119, Appendix 
K – Enrollment 
Form 
Follow-up Windows 
6 month window extended to ±30 
days; 12, 18 and annual follow-ups 
extended to ± 60 days. 
FDA Request #10 – 
Conditional Letter from 
10 Sept 2008 
22 
Neurologic 
Assessment 
Changed the NIHSS limit: When a 
change of 2 or more is noted, a 
neuro assessment is required. 
FDA Request #11 – 
Conditional Letter from 10 
Sept 2008 
27 
Major Bleeding 
Adverse Event 
Definition 
Reduce the transfusion limit from 
greater than 2 units transfusion to 
any transfusion triggers an event. 
FDA Request #12 – 
Conditional Letter from 10 
Sept 2008 
37, Appendix K – 
Adverse Event 
form 
Efficacy 
Performance 
Requirement 
Defined an analysis including 
responders, non responders and 
indeterminants. 
FDA Request #13 – 
Conditional Letter from 10 
Sept 2008 
45 
NA 
Typos and grammar correction. 
Administrative 
Throughout 
 
Version 6 (PRO 02291-F) was created in response to FDA questions and incorporates the 
changes below. This version will be sent to sites when Final FDA approval is received. 
 
Version 5 
Version 6 
Justification for Change 
Page(s) 
Efficacy 
Performance 
Requirement 
Further revised the analysis 
including responders, non 
responders and indeterminants based 
on FDA feedback. 
FDA Request #13 – 
Conditional Letter from 10 
Sept 2008 
45 
Adverse Event 
Definitions 
Removed reference to VAD, LVAD 
and blood contacting surfaces where 
appropriate as the C-Pulse does not 
have blood contacting surfaces and 
is more commonly a MCSD. 
Feedback from the CEC 
members and the need to 
provide clarification. 
38-41 

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Version 7 (PRO 02291-G) was created to add a seventh US site. In addition personnel and 
contact information was updates. During this review several clarification and typographical 
items were noted and corrected. This version will be sent to sites when Final FDA approval is 
received. 
 
Version 6 
Version 7 
Justification for Change 
Page(s) 
6 US centers 
Up to 7 centers in the United States 
(US) and potentially some Outside 
the United States (OUS) centers. 
Reference minutes from 
FDA Conference Call 
Requesting additional site 
and potential use of OUS 
data – Call 12/09/09 
6, 14, 19, 73, 
82, 114, 134 
Study duration\18 – 
24 months 
24– 30 months 
Slow enrollment. 
6, 15, 117 
Sponsor Address 
CEO Name and 
Contact Information 
Sponsor Clinical 
Contact Name and 
Contact Information 
CRO Contact 
Information 
Current 
Sponsor Address 
CEO Name and Contact 
Information 
Sponsor Clinical Contact Name and 
Contact Information 
CRO Contact Information 
Updated based on changes 
which have occurred since 
last IP update 
5, 60 
-- 
Table 3 – Added SVR under Right 
heart catheterization 
Removed Driver 
NYHA Class Assessment – made 
heading match text 
Clarifications and 
Typographical Errors 
23, 29, 36 
Appendix C – 
Participating 
Institutions 
Appendix C 
Participating 
Institutions 
Updated to Current PIs 
and contact information 
73 
Appendix H – 
Sample Informed 
Consent 
Appendix H – 
Sample Informed Consent 
Updated to include current 
information in the IP 
81 
Appendix I – 
Required Tests 
Appendix I – 
Required Tests 
Updated to include current 
information in IP 
94 
Appendix P – 
Six Minute Hall 
Walk 
Appendix P – 
Six Minute Hall Walk 
Updated to include current 
information in IP 
110 
Appendix R: Study 
Summary 
Appendix R: Study Summary 
Updated to include current 
information in IP 
114 

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Version 8 (PRO 02291-H) was created as an expansion protocol to add twenty (20) additional 
patients and two (2) additional sites. In addition, contact information was updated and a 1 – 5 
year follow-up was revised to include an ECHO. During this review several clarification and 
typographical items were noted and corrected. This version will be sent to sites when Final FDA 
approval is received. 
 
Version 7 
Version 8 
Justification for Change 
Page(s) 
7 US centers 
Up to 9 centers in the United States 
(US) and potentially some Outside 
the United States (OUS) centers. 
Expansion protocol 
6, 15, 20, 77, 
87, 121, 124 
20 patients implanted 
and 30 patients 
consented 
40 patients implanted and 60 
patients consented 
Expansion protocol 
6, 15, 87, 121, 
124 
24 – 30 months 
duration 
36 months duration 
Expansion protocol and 
slow enrollment 
6, 16, 124 
Sponsor Address 
CEO Name and 
Contact Information 
Sponsor Clinical 
Contact Information 
Current 
Sponsor Address and contact 
information 
CEO Address and Contact 
Information 
Updated based on changes 
which have occurred since 
last IP update 
5, 63 
No ECHO after 6 
mth follow-up 
ECHO added to 12, 18 months and 
2, 3, 4, and 5 year follow-u 
ps 
Updated to include 
Corelab ECHOs at all 
follow-ups 
26, 28, 101, 
128 
Table 1 
“3 sizes to fit 
ascending aorta 
outside diameter 28– 
40 millimeter (mm)” 
“3 sizes to fit ascending aorta 
outside diameter 29–40 millimeter 
(mm)” 
Typographical Error, 
changed to align with 
Inclusion/Exclusion 
Criteria 
12, 123 
Figure 1A 
Study Design 
Removed Number of Implants 
Clarification for the 
purpose of the Figure to 
describe the process 
15, 124 
Hospital Discharge 
Criteria 
“ventricular rates <10bpm” changed 
to read “ventricular rates <120bpm” 
Typographical Correction 
109 
Appendix C – 
Participating 
Institutions 
Appendix C 
Participating Institutions 
Updated to Current PIs 
and contact information 
77 
Appendix D – IRB 
List 
Appendix D - 
IRB List 
Updated to Current IRB 
List 
78 

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Version 9 (PRO 02291-I) was created to extend the follow up period from 5 to 10 years to 
accommodate follow up beyond 5 years. Appendix U of Version 9 was updated to reflect current 
infection control guidelines. 
 
Version 8 
Version 9 
Justification for Change 
Page(s) 
8 -9, 11, 13 - 15, 17 - 19, 21, 
23, 25 – 27, 30 – 33, 35 - 45, 
48, 53 – 60, 62 -64, 66, 70 -71, 
74-76 
Appendix D – Page 80 
Adjust formatting, correct 
Adjust pagination and 
Appendix E – Page 81 - 83 
-- 
spelling and other 
grammatical edits 
correct spelling and other 
minor edits. 
Appendix H – Page 87 - 88, 
90 - 92, 96, 99 
Appendix N – Page 114, 116 
Appendix Q – Page 122 - 123 
Appendix R – Page 124 - 125, 
128 
Appendix V – Page 150 
Trial Contact 
Information 
Address and contact 
information 
Update the Manufacturer 
address and study contact 
information 
7, 65 
5 year follow up 
10 year follow up 
Accommodate follow up 
of patients with full or 
partial C-Pulse system 
beyond 5 years 
8, 17 -18, 25 -26, 28 - 29 
Appendix I – Page 103 - 104, 
Appendix R – Page 123, 126, 
130 
Appendix H 
10 year follow up 
Additional surveillance 
imaging for suspected 
infection 
Per guidance from 
Infection Advisory 
Committee 
Appendix H – Page 88, 94, 96 
Appendix U 
Appendix U with revised 
infection control guidelines 
Update infection control 
guidelines to align with 
current practice 
Appendix U – Page 136 - 144