Quartet Lead and Resynchronization Therapy Options - Assessing the Response Rate at 6 Months in CRT Patients Implanted With a Quartet Left Ventricular(LV) Quadripolar Lead and the MultiPoint Pacing (MPP) Feature Activated
Phase: NA
Conditions: Heart Failure
Sponsor: Abbott Medical Devices

Clinical Investigation Plan Cover Page
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott.
87173 CIP Posting Cover Page Ver B
Template
Page 1 of 1
NCT Number: NCT02476201
QUARTO III
Quartet Lead and Resynchronization Therapy Options - Assessing the response rate at 6 months in
CRT patients implanted with a QuartetTM LV quadripolar lead and the MultiPointTM Pacing (MPP)
feature activated
Study Document No: SJM-CIP-100058
Version A
Date: 21-APR-2015
Sponsor
St. Jude Medical España/ Abbott Medical España
Avenida de Burgos 91
28050 Madrid Spain
Tel: +34 91 917 278 9 45

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP 
         Page 1 of 87 
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without the express written consent of St. Jude Medical 
Reference: 
CRD_789 
QUARTO III 
“Quartet Lead and Resynchronization Therapy Options - Assessing the response rate at 6 
months in CRT patients implanted with a QuartetTM LV quadripolar lead and the 
MultiPointTM Pacing (MPP) feature activated” 
“QUARTO III Substudy: Assessing the acute hemodynamic improvement in CRT 
patients implanted with a QuartetTM LV quadripolar lead and the MultiPointTM Pacing 
(MPP) feature activated” 
Clinical Investigation Plan (CIP) 
Sponsor 
St. Jude Medical España 
C/ Francisca Delgado 11 
Núcleo 3-3º. Arroyo de la Vega 
28108 – Alcobendas 
Madrid, Spain 
Tel: +34 91 458 47 77 
Fax: +34 91 344 17 08 
Clinical Coordinating 
Investigator
Dr. Javier Alzueta 
Rodríguez 
Hospital Clínico Universitario 
Virgen de la Victoria, Málaga, 
Spain 
Phone: +34 951 03 20 00 
Dr Joaquín Osca Asensi 
Hospital Universitari i Politècnic 
La Fe, Valencia, Spain 
Phone: +34 961 24 40 00 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
                                                                                                       Page 2 of 87  
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without the express written consent of St. Jude Medical  
 
PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
Clinical Investigational Plan Quarto III study 
 
Version A 
Reference #: CRD_789 
 
I have read and agree to adhere to the clinical investigational plan and all regulatory requirements 
applicable in conducting this clinical study. 
 
 
Principal Investigator 
 
Printed name: 
____________________________________ 
Signature: _______________________________________ 
Date:  ____________________ 
 
Principal Investigator 
 
Printed name: 
____________________________________ 
Signature: _______________________________________ 
Date:  ____________________ 
 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
                                                                                                       Page 3 of 87  
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without the express written consent of St. Jude Medical  
 
Coordinating Investigator/ National Investigator/ Medical Advisor 
SIGNATURE PAGE 
 
 
Clinical Investigational Plan Quarto III study 
 
Version A 
Reference #: CRD_789 
 
 
I have read and agree to adhere to the clinical investigational plan and all regulatory requirements 
applicable in conducting this clinical study.   
 
 
Coordinating Investigator/Medical Advisor, PI, etc.   
 
Printed name: 
____________________________________ 
 
Signature: _______________________________________ 
 
Date:  ____________________ 
 
 
Coordinating Investigator/Medical Advisor, PI, etc.   
 
Printed name: 
____________________________________ 
 
Signature: _______________________________________ 
 
Date:  ____________________ 
 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
                                                                                                       Page 4 of 87  
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Contents 
1.0 
Synopsis ................................................................................................................................................................... 7 
1.1 Substudy synopsis .............................................................................................................................................. 11 
1.2 Study Flow Chart ................................................................................................................................................ 13 
1.3 Study Contacts .................................................................................................................................................... 14 
2.0 
Background and Justification for Clinical Study ................................................................................................... 15 
3.0 
Risks and Benefits of the Clinical Study ................................................................................................................ 17 
3.1 Description of subject population ....................................................................................................................... 17 
3.2 Anticipated clinical benefits ............................................................................................................................... 17 
3.3 Anticipated adverse events and adverse device effects ...................................................................................... 17 
3.4 Risks associated with participation in the clinical study .................................................................................... 19 
3.5 Possible interactions with concomitant medical treatments and/or concurrent medical interventions ............... 19 
3.6 Steps that will be taken to control or mitigate the risks ...................................................................................... 20 
3.7 Risk-to-benefit rationale ..................................................................................................................................... 20 
3.8 Description of history of modifications or recall in relation to safety and clinical performance for device under 
investigation ................................................................................................................................................................ 20 
4.0 
Study Design .......................................................................................................................................................... 20 
4.1 Purpose ............................................................................................................................................................... 20 
4.2 Study Design and Scope ..................................................................................................................................... 20 
4.2.1 
Number of subjects required to be included in the study ............................................................................ 21 
4.2.2 
Estimated time needed to enroll this subject population ............................................................................. 21 
4.3 Objectives ........................................................................................................................................................... 22 
4.3.1 
Primary Objective ....................................................................................................................................... 22 
4.3.2 
Secondary Objective ................................................................................................................................... 22 
4.3.3 
Substudy Objective ..................................................................................................................................... 22 
4.4 Endpoints ............................................................................................................................................................ 22 
4.4.1 
Primary Endpoint ........................................................................................................................................ 22 
4.4.2 
Secondary Endpoint .................................................................................................................................... 22 
4.4.3 
Substudy Endpoint ...................................................................................................................................... 23 
4.5 Inclusion and Exclusion Criteria ........................................................................................................................ 23 
4.5.1 
Inclusion Criteria ........................................................................................................................................ 23 
4.5.2 
Exclusion Criteria ....................................................................................................................................... 24 
4.5.3 
Substudy Inclusion Criteria ......................................................................................................................... 24 
4.5.4 
Substudy Exclusion Criteria ........................................................................................................................ 24 
4.6 Subject Population .............................................................................................................................................. 25 
4.6.1 
Subject Screening ........................................................................................................................................ 25 
4.6.2 
Point of Enrollment ..................................................................................................................................... 25 
4.7 Informed Consent Process .................................................................................................................................. 26 
4.7.1 
General process ........................................................................................................................................... 26 
5.0 
Device under Investigation and Control/Comparators (if applicable) .................................................................... 26 
5.1 Device Description ............................................................................................................................................. 26 
5.2 Device Handling & Storage ................................................................................................................................ 28 
6.0 
Procedures .............................................................................................................................................................. 29 
6.1 Study Flow Chart ................................................................................................................................................ 29 
6.2 Procedures .......................................................................................................................................................... 30 
6.3 Enrollment Visit ................................................................................................................................................. 34 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
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6.4 Baseline Visit (within 7 days of Enrollment) ..................................................................................................... 35 
6.5 Implant visit (within 7 days of Enrollment) ....................................................................................................... 36 
6.6 Substudy Visit (within 7 days of the Implant) .................................................................................................... 36 
6.7 Six Month Follow-up visit (In Clinic, 180 days +/- 30 days from device implant) ............................................ 37 
6.8 Unscheduled Visits (In Clinic) ........................................................................................................................... 37 
6.9 Description of activities performed by Sponsor Representatives ....................................................................... 37 
6.10 Subject study completion.................................................................................................................................... 38 
6.11 Any Known or Foreseeable Factors that May Compromise the Outcome of the Clinical Study or the Interpretation 
of the Results ............................................................................................................................................................... 38 
6.12 Criteria and Procedures for Subject Withdrawal or Discontinuation.................................................................. 38 
7.0 
Compliance to Clinical Investigation Plan (CIP) ................................................................................................... 39 
7.1 Statements of Compliance .................................................................................................................................. 39 
7.2 Adherence to the Clinical Investigation Plan ..................................................................................................... 40 
7.3 Repeated and serious non-compliance ................................................................................................................ 41 
8.0 
Adverse Event, Adverse Device Effect .................................................................................................................. 41 
8.1 Definitions .......................................................................................................................................................... 41 
8.1.1 
Medical device ............................................................................................................................................ 41 
8.1.2 
Adverse Event (AE) .................................................................................................................................... 42 
8.1.3 
Serious Adverse Event (SAE) ..................................................................................................................... 42 
8.1.4 
Adverse Device Effect (ADE) .................................................................................................................... 42 
8.1.5 
Serious Adverse Device Effect (SADE) ..................................................................................................... 43 
8.2 Procedure for assessing, recording and reporting adverse events, adverse device effects, serious adverse events and 
serious adverse device effects: .................................................................................................................................... 43 
8.3 Subject Death ..................................................................................................................................................... 44 
8.3.1 
Procedure for recording and reporting subject death .................................................................................. 44 
9.0 
Data Management .................................................................................................................................................. 45 
9.1 Data Management Plan ....................................................................................................................................... 45 
9.2 Document and data control ................................................................................................................................. 46 
9.2.1 
Traceability of documents and data ............................................................................................................ 46 
9.2.2 
Recording data ............................................................................................................................................ 46 
10.0 Monitoring ............................................................................................................................................................. 46 
11.0 Regulatory Inspections ........................................................................................................................................... 47 
12.0 Statistical considerations ........................................................................................................................................ 47 
12.1 Statistical design, hypotheses, method and analytical procedures ...................................................................... 47 
12.2 Sample size ......................................................................................................................................................... 47 
12.3 Statistical hypotheses, method and analytical procedures for Sub-study endpoint............................................. 48 
12.4 Pass/fail criteria to be applied to the results of the clinical study ....................................................................... 48 
12.5 The provision for an interim analysis, when applicable ..................................................................................... 48 
12.6 Criteria for the termination of the clinical study on statistical grounds .............................................................. 48 
12.7 Procedures for reporting any deviation(s) from the original statistical plan ....................................................... 48 
12.8 The specification of subgroups for analysis ....................................................................................................... 49 
12.9 Procedures that take into account all the data ..................................................................................................... 49 
12.10 
The treatment of missing, unused or spurious data, including drop-outs and withdrawals ......................... 49 
12.11 
The exclusion of particular information for the testing of the hypothesis, if relevant, and ......................... 49 
12.12 
In multi-center studies, the minimum and maximum number of subjects to be included for each center .. 49 
13.0 Document Retention .............................................................................................................................................. 49 
14.0 Amendments to Clinical Investigational Plan ........................................................................................................ 50 
15.0 Outsourcing of duties and functions ....................................................................................................................... 50 
15.1 Echocardiography Core Lab ............................................................................................................................... 50 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
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16.0 Investigation Suspension or Termination ............................................................................................................... 50 
16.1 Premature termination of the whole clinical study or of the clinical study in one or more investigational sites.50 
16.2 Resuming the study after temporary suspension ................................................................................................ 52 
16.3 Study conclusion ................................................................................................................................................ 52 
17.0 Publication Policy .................................................................................................................................................. 52 
18.0 Bibliography .......................................................................................................................................................... 53 
Appendix A: Abbreviations .............................................................................................................................................. 56 
Appendix B: CIP Revision History ................................................................................................................................... 58 
Appendix C: Declaration of Helsinki................................................................................................................................ 59 
Appendix D: Programming Guidelines............................................................................................................................. 65 
Part 1 – MPP Cathode selection .................................................................................................................................. 65 
Part 2 – MPP  Delays programming................................................................................................................................ 72 
Part 3 – MPP Capture Thresholds Test ............................................................................................................................ 75 
Appendix E: Data Collection Method ............................................................................................................................... 77 
Appendix F: List of Clinical Investigation Sites and IRB/EC .......................................................................................... 85 
Appendix G: Sample Informed Consent ........................................................................................................................... 86 
Appendix H: Case Report Forms ...................................................................................................................................... 87 
 
 
 
 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
                                                                                                       Page 7 of 87  
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1.0 SYNOPSIS  
 
Title: 
QUArtet lead and Resynchronization Therapy Options III 
Acronym: 
QUARTO III study 
Purpose: 
The purpose of the study is to assess prospectively at 6 months the 
percentage 
of 
responder 
patients 
implanted 
with 
a 
Cardiac 
Resynchronization Therapy CRT-D device and a QuartetTM Left 
Ventricular (LV) quadripolar lead and with the MultiPointTM Pacing 
(MPP) feature activated. 
 
Objectives: 
To assess prospectively the changes in left ventricular function at 6 months 
in patients with the MultiPointTM Pacing (MPP) feature activated. 
Endpoints: 
Primary Endpoint 
 
The primary endpoint of the study is to measure prospectively at 6 months 
the percentage of responder* patients implanted with a QuartetTM LV 
quadripolar lead and with the MultiPointTM Pacing feature activated (using 
the electrical delay programing approach or anatomical approach) 
compared with No Pacing at baseline. 
 
*A positive CRT response is defined as an improvement of >15 % in Left 
Ventricular End Systolic Volume (LVESV) at 6 months post-implant, 
measured by Echocardiography. 
 
 
Secondary Endpoints 
− Reverse LV remodeling, measured as changes in LVESV, Left 
Ventricular End Diastolic Volume (LVEDV), Left Ventricular End 
Systolic Diameter (LVESD), Left Ventricular End Diastolic 
Diameter (LVEDD) and Left Ventricular Ejection Fraction (LVEF) 
at 6 months with MPP compared to No Pacing at Baseline 
o Comparison of the above mentioned echo parameters with the 
patient cohort stratified by etiology (ischemic versus non 
ischemic patients) 
− Percentage of super-responders** at 6 months in MPP  
− Dyssynchrony measured by the strain rate (speckle tracking 
echocardiography) between the anteroseptal segment and the 
posterior wall. 
− LV lead position  
o Short axis (posterolateral, lateral, anterolateral)  
o Long axis (apical, midventricular, basal) 
− New York Heart Association (NYHA) class changes at 6 months 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
                                                                                                       Page 8 of 87  
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− All-cause mortality at 6 months 
− All-cause, cardiovascular and/or heart failure hospitalization rate at 
6 months 
− Combined endpoint of mortality and heart failure hospitalization at 
6 months 
− Combined endpoint of mortality and cardiovascular hospitalization 
at 6 months. 
 
**Super-responder is defined as a patient with a mean absolute LVEF 
increase of >14% at 6 months post-implant compared with No Pacing at 
Baseline. 
Design: 
The investigation is a post-marketing, prospective, multicenter, regional, 
and non-randomized study. 
 
Data will be collected at Enrollment, Baseline, Implant, Unscheduled 
visits and 6 Month Follow-Up. Patients will exit the study after a 
completed 6 Month Follow-Up Visit. 
 
During the Enrollment visit, the Inclusion/Exclusion criteria will be 
verified and the Informed Consent Procedure will be performed. Patients 
will start their participation in the study once they sign the Informed 
Consent, prior to the CRT-D implantation.  
 
During the Baseline visit, demographic data, medical history, and 
cardiovascular 
medication 
will 
be 
collected. 
Echocardiography 
measurements will be collected following the Echo protocol and will be 
evaluated by an Echo Core Lab. At Implant procedure, the procedure 
details will be collected and the MPP feature will be turned ON.  
 
During the 6 Month visit, clinical and Echocardiography data will be 
collected. The Echo Core Lab will analyze the data to assess the 
percentage of responder and non-responder patients, according to LVESV 
reduction.  
The total duration of the study is expected to be approximately 2 years 
with about 1,5 years of enrollment and 6 months of Follow-up for the last 
patient enrolled.  
 
The clinical study will be conducted in approximately 12 sites in Spain and 
Portugal. 
 
Approximately 90 subjects will be enrolled in this study. 
 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
                                                                                                       Page 9 of 87  
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Devices used: 
All subjects will be implanted with a CE-approved St. Jude Medical CRT-
D device compatible with MultiPointTM Pacing feature (models n° 
CD3371-40(Q), CD3371-40(QC) or any other St Jude Medical model 
compatible with the MPP algorithm) and St. Jude Medical quadripolar left 
ventricular lead (Quartet 1458Q or newer). Future devices with MPP 
feature may be added once are market release. 
All of the devices used in this investigation have received appropriate 
regulatory certification (are CE marked and market released). 
 
Study Population 
Patients meeting all the Inclusion and none of the Exclusion criteria will be 
fully informed about the investigation and asked to participate in the 
investigation. In case the patient agrees, a duly signed and dated Patient 
Informed Consent form will be obtained. 
A patient becomes a subject once he/she has been fully informed about the 
study, has agreed to participate, signed & dated the consent. 
 
Inclusion/Exclusion 
Criteria  
Inclusion Criteria 
− Patient that will be implanted with a CRT-D with the MultiPointTM 
Pacing (MPP) feature under the current ESC or ACCF/AHA/HRS 
Class I or Class IIa indications for CRT-D implant (including 
upgrades from single or dual chamber ICD or PM). 
− Patient that will be implanted with a QuartetTM Left Ventricular 
(LV) quadripolar lead. 
− In sinus rhythm at baseline visit.  
− Patients with Left Bundle Branch Block (LBBB) 
− Must be willing and able to comply with study requirements. 
− Older than 18 years  
− Must indicate their understanding of the study and willingness to 
participate by signing an appropriate informed consent form. 
 
Exclusion Criteria 
− Already has a CRT device implanted.  
− Myocardial Infarction or unstable angina within 40 days prior the 
enrollment. 
− NYHA Class IV  
− Recent cardiac revascularization (PTCA, Stent or CABG) in the 4 
weeks prior to enrollment. 
− Cerebrovascular Accident (CVA) or Transient Ischemic Attack 
(TIA) in the 3 months prior the enrollment. 
− Classification of Status 1 for cardiac transplantation or 
consideration for transplantation over the next 12 months. 
− Primary valvular disease requiring surgical intervention. 
− Atrial Fibrillation (AF): 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
                                                                                                       Page 10 of 87  
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o 
Persistent AF at the time of enrollment or 30 days prior the 
enrollment 
o 
Permanent AF not treated with AV node ablation within 2 
weeks after the CRT-D implant 
o 
History or incidence of Paroxysmal or Persistent AF within 30 
days prior the enrollment 
− Patient for whom suitable Ttransthoracic echocardiographic images 
for determining the cardiac output (CO) and LV volumes cannot be 
obtained. 
− Undergone a cardiac transplantation or being waiting for it 
− Life expectancy < 6 months 
− Pregnancy or planning to become pregnant 
− Unable to comply with the follow up schedule 
− Currently participating in any other clinical investigation. 
 
Data Collection 
Data will be collected at Enrollment, Baseline, Implant, Unscheduled visits 
and 6 Month FU as follows: 
 
 
                                           
 
 
 
The following  forms will be used:  
§ If applicable 
 
 
Baseline 
visit 
Implant Visit 
Unscheduled 
6 Months 
Enrollment Form 
Baseline Form 
Implant Form 
Follow Up Form 
Deviation Form 
Adverse Event Form 
Hospitalization form 
System Revision Form 
Withdrawal Form 
Death Form 
√ 
√ 
- 
- 
√§ 
√§ 
√§ 
√§ 
√§ 
√§ 
 
- 
- 
√ 
- 
√§ 
√§ 
√§ 
√§ 
√§ 
√§ 
- 
- 
- 
√ 
√§ 
√§ 
√§ 
√§ 
√§ 
√§ 
 
- 
- 
- 
√ 
√§ 
√§ 
√§ 
√§ 
√§ 
√§ 
 
 
 
Enrollment 
Baseline  
Unscheduled 
Visit 
6M FU 
Implant 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
                                                                                                       Page 11 of 87  
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1.1 Substudy synopsis 
 
Substudy Purpose: 
The purpose of the substudy is to assess the acute hemodynamic 
improvement in patients implanted with a CRT-D device and a QuartetTM 
LV quadripolar lead with the MultiPointTM Pacing (MPP) feature activated. 
 
Substudy Objectives: The objective of the substudy is to assess the percentage of patients who 
achieve a greater hemodynamic response, measured by Cardiac Output 
(CO), with a MPP/SPP configuration compared to No Pacing. 
 
Substudy Endpoints: 
Primary Endpoint 
 
The primary endpoint of the substudy is to assess the percentage of patients 
who achieve the greater CO improvement with a MPP configuration and/or 
a Single Point Pacing (SPP) configuration versus No Pacing. The CO, 
based on Velocity Time Integral value (VTI by echocardiography) will be 
measured within 7 days after implant to evaluate the greater improvement 
in CO with the following configurations: 
• 
MPP Anatomical approach: choose the most anatomically 
separated vectors according to fluoroscopy images. 
• 
MPP Electrical approach: choose the most electrically 
separated vectors according to Auto VectSelect QuartetTM Test 
or Conduction Delays Test obtained by the CRT Tool kit. 
• 
Single Point Pacing (SPP): choose the vectors LV1 and LV2 of 
the approach with the best CO: 
o SPP with LV1 
o SPP with LV2 
Versus 
• 
NO pacing 
 
Substudy Design: 
The substudy will be conducted in approximately 3 centers out of the 
approximately 12 centers participating in the Quarto III Study in Spain.  
 
The total duration of the substudy is expected to be approximately 1 year. 
 
Approximately 30 subjects will be enrolled in this substudy. 
 
During the Substudy visit, within 7 days after the implant, an additional 
Echocardiography will be performed to a subgroup of 30 patients from 
some selected centers. This Echocardiography will not be sent to the Echo 
Core Lab but evaluated locally at hospital. 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
                                                                                                       Page 12 of 87  
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Substudy 
Inclusion/Exclusion 
Criteria  
Inclusion Criteria 
− Patients enrolled in the Quarto III Study from the centers 
participating in the substudy will be evaluated. 
Exclusion Criteria 
− The patient is not in sinus rhythm in the moment of the substudy 
visit. 
 
Substudy Data 
Collection 
Data from this hemodynamic measurements will be collected  within the 
first 7 days after the CRT-D Implantation: 
 
Specific Case Report Forms (CRF) will be used for substudy purposes. The 
following  forms will be used:  
 
 
 
 
 
 
 
 
 
 
§ If applicable 
 
                              
 
 
Substudy visit 
Substudy Enrollment Form 
Substudy Echo Form 
Deviation Form 
Adverse Event Form 
Hospitalization form 
Withdrawal Form 
Death Form 
√ 
√ 
√§ 
√§ 
√§ 
√§ 
√§ 
 
 
 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
                                                                                                       Page 13 of 87  
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1.2 Study Flow Chart 
 
 
 
 
 
 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
                                                                                                       Page 14 of 87  
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1.3 Study Contacts 
2.0 
Name 
Position 
Phone 
Mail 
Elena Llorente 
Clinical Manager 
+34 917278940 
Ellorente@sjm.com 
Antonio J Ruiz 
Clinical Project Leader 
+34 917278928 
Aruiz@sjm.com 
Pilar Santamaria 
Clinical Project Leader 
+34 917278964 
Psantamaria@sjm.com 
Beatriz Blanco 
Clinical Research Associate 
+34 917278973 
Bblanco@sjm.com 
Beatriz Segovia 
Clinical Trials Administrator +34 917278930 
Bsegovia@sjm.com 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
                                                                                                       Page 15 of 87  
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BACKGROUND AND JUSTIFICATION FOR CLINICAL STUDY 
Heart failure (HF) is defined by the European Society of Cardiology (ESC) 2012 guidelines [1] as an 
abnormality of cardiac structure or function leading to failure of the heart to deliver oxygen at a rate 
commensurate with the requirements of the metabolizing tissues, despite normal filling pressures (or 
only at the expense of increased filling pressures) [2]. For the purposes of these guidelines, HF is 
defined, clinically, as a syndrome in which patients have typical symptoms (e.g. breathlessness, ankle 
swelling, and fatigue) and signs (e.g. elevated jugular venous pressure, pulmonary crackles, and 
displaced apex beat) resulting from an abnormality of cardiac structure or function. Many of the 
symptoms of HF are non-discriminating and, therefore, of limited diagnostic value [3] [4] [5] [6] [7]. 
Many of the signs of HF result from sodium and water retention and resolve quickly with diuretic 
therapy, i.e. may be absent in patients receiving such treatment. Demonstration of an underlying 
cardiac cause is therefore central to the diagnosis of HF. This is usually myocardial disease causing 
systolic ventricular dysfunction. However, abnormalities of ventricular diastolic function or of the 
valves, pericardium, endocardium, heart rhythm, and conduction can also cause HF (and more than one 
abnormality can be present). Over 25% of patients with systolic heart failure have dyssynchronous 
ventricular contraction [8] that further impairs left ventricular (LV) systolic function, increases energy 
requirements, and results in progressive heart failure [9]. 
 
Heart failure is the most rapidly growing cardiovascular condition in developed countries [10] [11] 
[12]. It is estimated that in the Western world more than 20 million patients suffer from end-stage HF, 
so the prevalence of this syndrome is 2-2.5% overall, increasing up to 10% among persons 70 years of 
age or older [13]. HF is a major threat to public health affecting an estimated 14 million individuals in 
Europe and it is estimated that 50% of people diagnosed with HF will die within 5 years [1] [11] [14]. 
Cardiac resynchronization therapy (CRT) devices are designed to synchronize the mechanical activity 
of the ventricles, as well as that of the atria and ventricles (AV timing). In patients with a low ejection 
fraction (EF), reduced functional status, and delayed electrical conduction, CRT improves cardiac 
output (CO) and reduces symptoms [9] without increasing energy consumption [15] [16] [17] [18]. 
Resultant improvements in LV volumes (reverse remodeling) occur in some, but not all patients [19]. 
On average, CRT reduces mortality and recurrent admissions in patients with highly symptomatic heart 
failure, a low ejection fraction (EF), and a wide intrinsic QRS duration [20]. Several landmark clinical 
trials published in the past few years have provided compelling evidence that CRT can produce 
significant clinical benefits, including improvements in patients’ HF symptoms, quality of  life, 
reduced HF hospitalization, and echocardiographic measures which confer a mortality benefit [21] 
[22] [23]. 
Though a majority of treated patients shows a benefit, up to 40% derive no improvement from 
CRT. In the MIRACLE study, 34% of patients did not demonstrate an improvement in a HF clinical 
composite score (CCS) that combined all-cause mortality, HF related hospitalization, NYHA 
class and patient global assessment into an outcome measure [24]. A summary of non- responder 
rate from various clinical studies has been performed by Birnie and Tang [25]. Those rates of non-
response to cardiac resynchronization therapy are often quoted as 20-30% in the listed studies, but 
the authors suggest that the true non-responder rate may be as high as 40- 50%. This inconsistent 
CRT effectiveness may be due to incomplete resynchronization and the presence of Intraventricular 
dyssynchrony. 

Study Document No: SJM-CIP-10058 
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Study Name: QUARTO III study 
CIP  
 
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All major medical devices companies offer bipolar LV leads that have one ring electrode and one tip 
electrode that can be positioned via the coronary sinus. This traditional type of bipolar LV lead, 
when used in combination with right ventricular (RV) lead, may have up to six pacing vectors 
available to the physician for standard biventricular (BiV) pacing.  
St. Jude Medical developed a new family of quadripolar LV leads called Quartet® LV lead. The 
programmability is increased providing up to 10 different pacing vector options (VectSelect®) from 
the four pacing electrodes on the LV lead. Additionally St. Jude Medical has developed a new 
algorithm (MultiPoint™ pacing or MPP) which allows sequential pacing of the LV with two pacing 
vectors compared to one vector in a traditional CRT- D system. A combination of any two of the 10 
available vectors with inter-stimulus delays can be used. MPP via one LV lead may have the potential 
to act as an alternative to non-invasively optimize LV lead placement, and it may improve 
hemodynamics and the response to CRT. Studies showed that simultaneously exciting a larger mass or 
volume of cardiac tissue results in faster depolarization velocity and shorter left ventricular trans-
ventricular conduction times [23] [24]. In addition, by capturing a larger volume of cardiac muscle, the 
site of latest intrinsic activation within the left ventricle may be more likely to be depolarized early, 
resulting in better synchronization and maximizing cardiac output. 
 
Since MPP delivers two electrical impulses at programmable delays (LV1 and LV2) to two LV sites, 
the initial volume of excited cardiac tissue is increased. By capturing more mass at the site of 
initial depolarization there is a greater likelihood of pacing the site of latest systolic delay. Both 
of these methods have been shown to improve LV function [25] and it is believed that this additional 
improvement in LV function may benefit those patients who are otherwise identified as non- 
responders to conventional BiV pacing. 
 
This clinical investigation comes to collect information about the response rate achieve with this new 
technology compared with the traditional one. A substudy is designed as well to assess the acute 
hemodynamic improvement achieve with MultiPointTM Pacing (MPP) feature activated, following the 
investigational line of some other studies [26] like Quarto I [27] ,   

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3.0 RISKS AND BENEFITS OF THE CLINICAL STUDY 
The risks associated with the use of the Quadripolar CRT device system are anticipated to be 
comparable to those associated with the use of other currently available CRT devices, and leads. 
Patients participating in this study are indicated for a CRT system as part of their standard medical 
management and are subject to the risks associated with these devices. 
 
Additional risks associated with MPP compared to conventional BiV pacing are considered to be 
minimal. There is a theoretical risk that addition of a second LV pacing pulse could have a pro-
arrhythmic effect. However, among both preclinical and clinical experience, no arrhythmias have been 
reported that have been caused by MPP. The risk of reentrant conduction pathways and induced 
Ventricular Tachycardia (VT) is similar to that caused by standard BiV pacing. 
 
3.1 Description of subject population 
Patients meeting the Inclusion/Exclusion criteria will be fully informed about the investigation and 
asked to participate in the investigation. In case the patient agrees, a duly signed and dated Patient 
Informed Consent form will be obtained so the patient becomes a subject. 
3.2 Anticipated clinical benefits 
Patients enrolled in this investigation may benefit as it is expected that the MultiPointTM Pacing feature 
will increase the volume of excited cardiac tissue and by capturing more mass at the initial 
depolarization, there is a greater likelihood of pacing the site of latest systolic delay.  
Both of these methods have been shown to improve LV function and it is believed that this additional 
improvement in LV function may benefit those patients who are otherwise identified as non-responders 
to conventional BiV pacing 
 
3.3 Anticipated adverse events and adverse device effects 
Potential complications associated with the implantation of pulse generator system include, but are not 
limited to: 
 
− Acute hemorrhage/bleeding  
− Air emboli  
− Arrhythmia acceleration 
− Cardiac or venous perforation  
− Cardiogenic shock  
− Cyst formation 
− Erosion 
− Exarcerbation of heart failure 
− Extrusion 
− Fibrotic tissue growth 
− Fluid accumulation 

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− Hematoma formation  
− Histotoxic reactions  
− Infection  
− Keloid formation 
− Myocardial irritability  
− Nerve damage 
− Pneumothorax  
− Thromboemboli  
− Venous occlusion  
 
Other possible adverse effects include mortality due to:  
− Component failure 
− Device-programmer communication failure 
− Lead abrasion 
− Lead dislodgment or poor lead placement 
− Lead fracture 
− Inability to defibrillate 
− Inhibited therapy for a ventricular tachycardia 
− Interruption of function due to electrical or magnet interference 
− Shunting of energy from defibrillation paddles 
− System failure due to ionizing radiation 
 
Other possible adverse effects include mortality due to inappropriate delivery of therapy caused by: 
− Multiple counting of cardiac events including T-waves, P-waves, or supplemental pacemaker 
stimuli 
 
Among the psychological effects of the device implantation are imagined pulsing, dependency, fear of 
inappropriate pulsing and fear of losing pulse capability. 
 
These events are not unique to devices being used within this study and could occur during any device 
implant outside of the study 
 
Potential complications associated with the use of left ventricular leads are the same as with the use of 
any lead and include, but it is not limited to:  
− Allergic reaction to contrast media  
− Body rejection phenomena 
− Cardiac/coronary sinus dissection  
− Cardiac/coronary sinus perforation  
− Cardiac tamponade  
− Coronary sinus or cardiac vein thrombosis  
− Death  
− Endocarditis 

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Study Name: QUARTO III study 
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− Excessive bleeding  
− Hematoma/seroma 
− Induced atrial or ventricular arrhythmias  
− Infection  
− Lead dislodgment  
− Local tissue reaction; formation of fibrotic tissue 
− Loss of pacing and/or sensing due to dislodgment or mechanical malfunction of the pacing lead 
− Myocardial irritability 
− Myopotential sensing  
− Pectoral/diaphragmatic/phrenic nerve stimulation  
− Pericardial effusion  
− Pericardial rub  
− Pneumothorax/hemothorax 
− Prolonged exposure to fluoroscopic radiation  
− Pulmonary edema  
− Renal failure from contrast media used to visualize coronary veins  
− Rise in threshold and exit block  
− Thrombotic or air embolism  
− Valve damage  
 
Performance of a coronary sinus venogram is unique to lead placement in the cardiac venous system, 
and carries risks. Potential complications reported with direct subclavian venipuncture include 
hemothorax, laceration of the subclavian artery, arteriovenous fistula, neural damage, thoracic duct 
injury, cannulation of other vessels, massive hemorrhage, and rarely, death.  
 
These events are not unique to study procedures and could occur during any lead implant outside of the 
study. 
 
3.4 Risks associated with participation in the clinical study 
All of the devices used in this investigation have received appropriate  regulatory certification (are CE 
marked and market released).The risks associated with the use of the Quadripolar CRT device system 
are anticipated to be comparable to those associated with the use of other currently available CRT 
devices, and leads. Patients participating in this study or substudy are indicated for a CRT system as 
part of their standard medical management and are subject to the risks associated with these devices. 
 
3.5 Possible interactions with concomitant medical treatments and/or concurrent medical 
interventions 
It is not anticipated any additional interaction with concomitant medical treatments and/or concurrent 
medical intervention than with a regular CRT-D device treatment. The patients are all candidate to a 
CRT-D device implant, so any additional risk will be added by the fact of participating in this clinical 
investigation. 

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Anyway, the Principal Investigator (PI) from each participant center will evaluate any potential 
interaction with concomitant medical treatments and/or concurrent medical interventions and will 
inform the sponsor.  
 
3.6 Steps that will be taken to control or mitigate the risks 
This protocol should be followed unless the safety and the availability of the patient do not allow it. 
Any protocol deviation will be documented accordingly and communicated to the sponsor as soon as 
possible. 
 
3.7 Risk-to-benefit rationale 
The risks associated with the use of the Quadripolar CRT device system are anticipated to be 
comparable to those associated with the use of other currently available CRT devices, and leads. 
Patients enrolled in this investigation may benefit from  the MultiPointTM Pacing feature as reported 
in the literature.Implantation of this system may offer certain advantages as compared to conventional 
CRT system. The clinical benefits for this new system outweigh the risks and thus provide 
justification for proceeding with this clinical study. 
 
3.8 Description of history of modifications or recall in relation to safety and clinical 
performance for device under investigation 
Up the date of this protocol, there has not been any history of modifications or recall in relation to 
safety and clinical performance for the devices in investigation. 
 
4.0 STUDY DESIGN 
4.1 Purpose 
The purpose of this study is to assess prospectively at 6 months the percentage of responder patients 
implanted with a CRT-D device and a QuartetTM LV quadripolar lead and with the MultiPointTM 
Pacing (MPP) feature activated.  
 
A substudy will be carried on in some patients from the 3 selected centers with the intention to assess 
the acute hemodynamic improvement in patients implanted with a CRT-D device and a QuartetTM LV 
quadripolar lead and with the MultiPointTM Pacing (MPP) feature activated.  
 
4.2 Study Design and Scope 
This is a post-marketing, prospective, non-randomized, multicenter, regional study. Data will be 
collected at Enrollment, Baseline, Implant and 6 Month Follow-Up. Additionally, approximately 30 
patients from the selected centers, will participate in a substudy, so additional data will be collected at 
Substudy Visit within a window of 7 days after the implant.  

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During the Enrollment visit, the Informed Consent Procedure will be performed and the  
Inclusion/Exclusion criteria verified. During the Baseline Visit, the Demographic data, Medical History 
and Cardiac Medication will be collected. Echocardiography measurements during intrinsic rhythm 
will be collected following the specific study Echocardiography protocol and will be evaluated by an 
Echo Core Lab. At Implant procedure data and MPP activation evaluation will be collected. 
All patients will begin their CRT treatment with the MPP feature turned ON. For those patients who 
are not able to implant the QuartetTM LV lead or not able to activate the MPP feature, a Termination 
will be done and their participation in the study will be concluded. 
During the Substudy visit, an additional Echocardiography will be performed to a subgroup of 30 
patients from some selected centers. This Echocardiography will not be sent/uploaded to the Echo Core 
Lab but evaluated locally at hospital. 
During the 6 Month visit, clinical and Echocardiography data will be collected. The Echo Core Lab 
will analyze the data to assess the percentage of responder and non-responder patients. The patient’s 
response to CRT will be evaluated according to LVESV reduction. Patients with a LVESV reduction 
in MPP compared with the data collected at baseline in No pacing of at least 15% will be classified as 
Responders. 
The total duration of the study is expected to be approximately 2 years with about 1,5 years of 
enrollment and 6 months of Follow-up for the last patient enrolled. 
 
The investigation will be conducted in approximately 12 centers from Spain and Portugal. It is 
expected to enroll approximately 90 patients. Approximately 30 of these patients will be analyzed 
within the substudy in approximately 3 centers.  
4.2.1 Number of subjects required to be included in the study  
It is expected to enroll approximately 76 patients. This amount of patients is required to achieve a 
75% of responder patents with MPP at 6 months, with a statistical power (1-beta) of 0.90 and risk 
level (alpha) of 0.025. Assuming that a 16% of patients will drop out of the study, the total sample 
size is 90 patients. Approximately 30 of these patients will be analyzed within the substudy. 
 
4.2.2 Estimated time needed to enroll this subject population 
The study may take up to 2 years (24 months), dependent on the rate of enrollment.  
 
 

Study Document No: SJM-CIP-10058 
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Study Name: QUARTO III study 
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4.3 Objectives 
To assess prospectively the changes in left ventricular function at 6 months in patients with the 
MultiPointTM Pacing (MPP) feature activated. 
 
4.3.1 Primary Objective 
The primary objective of the study is to assess prospectively the percentage of responder patients at 6 
months with the MultiPointTM Pacing (MPP) feature activated.  
 
4.3.2 Secondary Objective 
To assess the impact of MPP feature on patient’s functional and clinical status. 
 
4.3.3 Substudy Objective 
The objective of the substudy is to assess the percentage of patients who achieve a greater 
hemodynamic response, measured by Cardiac Output, with a MPP configuration or Single Point Pacing 
(SPP) compared to No Pacing within 7 days after implant. 
 
4.4 Endpoints 
4.4.1 Primary Endpoint 
The primary endpoint of the study is to measure prospectively at 6 months the percentage of responder 
patients implanted with a QuartetTM LV quadripolar lead and with the MultiPointTM Pacing feature 
activated (using the electrical delay programing approach or anatomical approach) compared with No 
Pacing at baseline.  
A positive CRT response is defined as an improvement of >15 % in Left Ventricular End Systolic 
Volume (LVESV) at 6 months post-implant, measured by Echocardiography. 
 
4.4.2 Secondary Endpoint 
The secondary endpoints of this study are: 
 
− Reverse LV remodeling, measured as changes in LVESV, Left Ventricular End Diastolic 
Volume (LVEDV), Left Ventricular End Systolic Diameter (LVESD), Left Ventricular End 
Diastolic Diameter (LVEDD) and Left Ventricular Ejection Fraction (LVEF) at 6 months with 
MPP compared with no pacing at Baseline 
o 
Comparison of the above mentioned echo parameters with the patient cohort stratified by 
etiology (ischemic versus non ischemic patients) 
− Percentage of super-responders** at 6 months in MPP  
− Dyssynchrony measured by the strain rate (speckle tracking echocardiography) between the 
anteroseptal segment and the posterior wall (if available) 

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− LV lead position  
o 
Short axis (posterolateral, lateral, anterolateral)  
o 
Long axis (apical, mid-ventricular, basal) 
− NYHA class changes at 6 months 
− All-cause mortality at 6 months 
− All-cause, cardiovascular and/or heart failure hospitalization rate at 6 months 
− Combined endpoint of mortality and heart failure hospitalization at 6 months 
− Combined endpoint of mortality and cardiovascular hospitalization at 6 months 
 
**Super-responder is defined as a patient with a mean absolute LVEF increase of >14% at 6 
months post-implant compared with No Pacing at Baseline. 
 
4.4.3 Substudy Endpoint 
The endpoint of the substudy is to assess the percentage of patients who achieve the greater CO 
improvement with a MPP configuration and/or SPP configuration compared to No Pacing. The CO, 
based on Velocity Time Integral value (VTI by echocardiography) will be measured within 7 days after 
implant to evaluate the greater improvement in CO with the following configurations: 
• 
MPP Anatomical approach: choose the most anatomically separated vectors according to 
fluoroscopy images.  
• 
MPP Electrical approach: choose the most electrically separated vectors according to Auto 
VectSelect QuartetTM Test or Conduction Delays Test obtained by the CRT Tool kit. 
• 
Single Point Pacing: choose the vectors LV1 and LV2 of the approach with the best CO 
o 
SPP with LV1 
o 
SPP with LV2 
Versus 
• 
NO pacing 
 
4.5 Inclusion and Exclusion Criteria 
A subject, who meets all of the inclusion criteria, and none of the exclusion criteria, is eligible to 
participate in this study. Those patients who agree to participate in the substudy at the selected centers 
will be candidates for being included in the substudy. 
 
4.5.1 Inclusion Criteria 
To participate in this clinical study, the subject must meet all of the following inclusion criteria: 
− Patients that will be implanted with a CRT-D with the MultiPointTM Pacing (MPP) feature 
under the current ESC or ACCF/AHA/HRS Class I or Class IIa indications for CRT-D 
implant (including upgrades from single or dual chamber ICD or PM). 
− Patient that will be implanted with a QuartetTM Left Ventricular (LV) quadripolar lead. 
− In sinus rhythm at baseline visit.  
− Patients with Left Bundle Branch Block (LBBB) 

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− Older than 18 years 
− Must be willing and able to comply with study requirements. 
− Must indicate their understanding of the study and willingness to participate by signing an 
appropriate informed consent form. 
 
4.5.2 Exclusion Criteria 
Subjects are not eligible for clinical study participation if they meet any of the following exclusion 
criteria: 
− Already has a CRT device implanted.  
− Myocardial Infraction or unstable angina within 40 days prior the enrollment. 
− NYHA Class IV 
− Recent cardiac revascularization (PTCA, Stent or CABG) in the 4 weeks prior to enrollment. 
− Cerebrovascular Accident (CVA) or Transient Ischemic Attack (TIA) in the 3 months prior the 
enrollment. 
− Classification of Status 1 for cardiac transplantation or consideration for transplantation over 
the next 12 months. 
− Primary valvular disease requiring surgical intervention. 
− Atrial Fibrillation (AF): 
o Persistent AF at the time of enrollment or 30 days prior the enrollment. 
o Permanent AF not treated with AV node ablation within 2 weeks after the CRT-D 
implant 
o History or incidence of Paroxysmal or Persistent AF within 30 days prior the 
enrollment 
− Patient for whom suitable transthorathic echocardiographic images for determining the cardiac 
output and LV volumes cannot be obtained. 
− Undergone a cardiac transplantation or being waiting for it 
− Life expectancy < 6 months 
− Pregnancy or planning to become pregnant 
− Unable to comply with the follow up schedule 
− Currently participating in any other clinical investigation. 
 
4.5.3 Substudy Inclusion Criteria 
To participate in the substudy the subject must meet the following inclusion criteria:  
− Patients enrolled in the Quarto III Study from the centers participating in the substudy. 
4.5.4 Substudy Exclusion Criteria 
Subjects are not eligible for the substudy if they meet the following exclusion criteria: 
− The patient is not in sinus rhythm in the moment of the substudy visit. 
 
 

Study Document No: SJM-CIP-10058 
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4.6 Subject Population 
4.6.1 Subject Screening 
All subjects presented at the investigational site can be screened by a member of the investigational 
team previously trained on the CIP and delegated to do so. 
Subjects who do not meet the inclusion/exclusion criteria will not be eligible to participate in this 
study. 
Subjects meeting the inclusion/exclusion criteria will be fully informed about the study and asked to 
participate in the study. In case the subject agrees, a duly signed and dated Patient Informed Consent 
will be obtained. 
 
Once the eligible subject has signed the Informed Consent and completed the Baseline visit, 
he/she will advance to the Implant Procedure visit in which the CRT-D device implant and MPP 
activation tests will be performed. Depending on the result of this test, the subjects will be 
classified as: 
 
• Implant Failure: 
Patients who provided the Informed Consent, meet the Inclusion/Exclusion criteria, but do not 
receive the CRT-D MPP compatible device or LV lead because of implant failure or physician’s 
decision. These patients’ participation into the study will be terminated immediately. 
 
• MPP Activation Failure: 
Patients who provided the Informed Consent, meet the Inclusion/Exclusion Criteria, have been 
implanted with a CRT MPP compatible device but not enough MPP vector combinations are possible 
to allow the MPP activation or the investigator decided not to program the MPP feature ON. These 
patient’ participation to the study will be terminated immediately. 
 
• Valid subject: 
Patients who provided the Informed Consent, meet the Inclusion/Exclusion criteria, have been 
implanted with a CRT MPP compatible device, have enough MPP vector combinations to allow the 
MPP activation and the MPP feature is programmed ON. These patients will proceed in the study and 
constitute the Study Population. 
 
4.6.2 Point of Enrollment 
Subjects are considered enrolled in the study from the moment the subject has provided written Patient 
Informed Consent, prior to the CRT-D implant. (Refer to the following Section for the Informed 
Consent Process).  
 

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4.7 Informed Consent Process 
4.7.1 General process 
Prior to enrolling in the clinical study and conducting study-specific procedures, all subjects will be 
consented, as required by applicable regulations and the center’s Institutional Review Board               
(IRB)/Ethics Committee (EC).  Informed consent must be obtained from each subject prior to any 
study related procedures. The consent form must be signed and dated by the subject and by the person 
obtaining the consent. 
 
The principal investigator or his/her authorized designee will conduct the Informed Consent Process. 
This process will include a verbal discussion with the subject on all aspects of the clinical study that are 
relevant to the subject’s decision to participate in the clinical study.  
 
The subject shall be provided with the informed consent form that is written in a language that is 
understandable to the subject and has been approved by the center’s IRB/EC.  Failure to obtain 
informed consent from a subject prior to study enrollment should be reported to St. Jude Medical 
within 5 working days and to the reviewing center’s IRB/EC/ consistent with the center’s IRB/EC 
reporting requirements.  
 
5.0 DEVICE 
UNDER 
INVESTIGATION 
AND 
CONTROL/COMPARATORS 
(IF 
APPLICABLE) 
5.1 Device Description 
All subjects will be implanted with a regulatory approved (CE marked and Market released) St. Jude 
Medical CRT device compatible with MultiPointTM Pacing feature (models n° CD3371-40(Q), 
CD3371- 40C(Q) or any other St Jude Medical (SJM) model compatible with the MPP algorithm) and 
St. Jude Medical quadripolar left ventricular lead (Quartet 1458Q or newer). 
During the follow-ups, implanted devices will be checked with Merlin® Patient Care System (PCS) 
(model 3650 or newer, software version 19.2.2 or newer) programmer.  
Any commercially available and regulatory approved right atrial and right ventricular leads can be 
used in this investigation.  
All of the devices used in this investigation, have received appropriate regulatory certification and are 
market released. 
The CRT-D devices are equipped with an IS4-LLLL low voltage connector to facilitate implantation 
of an IS4 LV four electrode lead. Also, devices with a Q suffix have a high voltage DF4-LLHH bore 
that allows the use of Durata DF4 lead. 
The Quartet™ LV lead is a quadripolar, over–the-wire design that enables implantation using either a 
stylet or guidewire. The lead has an open lumen and an opening at the lead tip to allow the use of a 
guidewire. The body has Optim™ lead insulation and a maximum lead body diameter of 5.1 Fr. Like 
the QuickSite® and Quickflex® left heart lead families, the distal portion of the Quartet™ is pre-
shaped in an “s-curve” shape to provide stabilization of the distal tip in the coronary veins of the left 

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Mid 2  
Mid 2  
Proximal  
Mid 3  
Distal  
Mid 3  
Mid 2  
Proximal 
Distal 
RVC 
Distal  
Mid 3  
Proximal  
ventricle. The outer lead body is covered with Fast-Pass™ coating that increases lubricity during 
initial implant. 
The titanium nitride (TiN) coated platinum/iridium (PtIr) tip electrode on the lead contains a 
molded ring that elutes steroid. Additionally, the surface of the tip electrode is coated with a thin 
steroid film to provide immediate steroid release. 
Three titanium nitride (TiN) coated platinum/iridium (PtIr) ring electrodes are located on the lead at a 
distance of 20 mm (Mid 2), 30 mm (Mid 3) and 47 mm (Proximal 4) from the tip of the lead. 
The lead provides pace/sense capability from 4 electrodes (tip and 3 rings): 
  
• Distal Tip (D1) 
• Mid 2 (M2)  
• Mid 3 (M3) 
• Proximal 4 (P4) 
 
 
 
 
 
 
 
 
The Quartet™ LV lead can be programmed with a combination of 10 possible pacing vectors using 
the Merlin™ PCS programmer: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vector Number 
Vector 
1 
D1 – M2 
2 
D1 – P4 
3 
D1 – RVCoil 
4 
M2 – P4 
5 
M2 – RVCoil 
6 
M3 – M2 
7 
M3 – P4 
8 
M3 – RVCoil 
9 
P4 – M2 
10 
P4 – RVCoil 

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5.2 Device Handling & Storage 
St. Jude Medical requires all investigational products be stored, according to the labeling, in a secure 
area to prevent unauthorized access or use.  This will prevent non-investigational use of products that 
are provided for this study. 
 
 

Study Document No: SJM-CIP-10058 
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6.0 PROCEDURES 
6.1  Study Flow Chart 
 
 
 
Figure 1: Flow Chart 

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6.2 Procedures 
The clinical study will be conducted in accordance with the CIP. All parties participating in the 
conduct of the clinical study will be qualified by education, training, or experience to perform their 
tasks and this training will be documented appropriately. The clinical study will not commence until St. 
Jude Medical receives written approval from the IRB/EC and relevant regulatory authorities and all 
required documents have been collected from the site(s).  
All the mandatory procedures are listed in the following tables and detailed in the next pages: 
*Only for selected Sites; (X) if applicable 
Table 1: List of all study specific activities/procedures 
 
                Visit 
Study 
Activity 
Enrollment 
Visit  
Baseline 
visit 
Implant Visit 
(within 7 
days) 
Substudy visit* 
(within 7 days of  
implant) 
Unscheduled 
FU 
6M 
Follow Up 
(+/- 30 days) 
Patient Informed Consent 
Process 
X 
 
 
 
 
 
Inc/Exc criteria  
X 
 
 
 
 
 
Patient Data and Medical 
History 
 
X 
 
 
 
 
Current Cardiac Medication 
 
X 
 
 
(X) 
X 
NYHA Class Evaluation 
 
X 
 
 
(X) 
X 
Core Lab Echocardiography  
 
X 
 
 
(X) 
X 
Implant Procedure Details 
 
 
X 
 
 
 
MPP Vector Test 
 
 
X 
 
(X) 
 
Conduction Delays Test 
 
 
X 
 
(X) 
X 
Device Interrogation and 
Programming 
 
 
X 
 
(X) 
X 
MPP Programming 
 
 
X 
 
X 
(X) 
Fluoroscopy Images 
 
 
X 
 
 
 
Substudy Inc/Exc criteria* 
 
 
 
X 
 
 
Substudy 
Echocardiography* 
 
 
 
X 
 
 
Adverse Event 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
Hospitalization 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
Protocol Deviation 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
Withdrawal 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
Death 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
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The Case Report Forms used to complete all the information detailed above are summarized in the 
table below: 
 
                      Visit 
 
 
CRFs 
 
Baseline 
Visit 
 
Implant Visit 
Substudy Visit* 
(within 7 days 
implant) 
Unscheduled 
6 Month 
(+/-30 days) 
Enrollment Form 
X 
- 
- 
- 
- 
Baseline Form 
X 
- 
- 
- 
- 
Implant Form 
- 
X 
- 
- 
- 
Substudy Enrollment Form* 
- 
- 
X 
- 
- 
Substudy Echo Form* 
- 
- 
X 
- 
- 
Follow Up Form 
- 
- 
- 
(X) 
X 
Deviation Form 
(X) 
(X) 
(X) 
(X) 
(X) 
Adverse Event Form 
(X) 
(X) 
(X) 
(X) 
(X) 
Hospitalization Form 
(X) 
(X) 
(X) 
(X) 
(X) 
System Revision Form 
(X) 
(X) 
(X) 
(X) 
(X) 
Withdrawal Form 
(X) 
(X) 
(X) 
(X) 
(X) 
Death Form 
(X) 
(X) 
(X) 
(X) 
(X) 
    *Only for selected sites; (X) if applicable 
Table 2: Case Report Forms (CRF) 
 
 
Informed Consent Procedure and Inclusion/Exclusion Criteria check: 
Patient’s  eligibility  criteria  and  Informed  consent  Procedure  is  performed  before  any study 
related activity.  
 
Patient Data and Medical History: 
Subject’s  demographic data  will  be  collected  at  the  Baseline  Visit  together  with cardiomyopathy 
etiology, implant indication and co-morbidities. 
 
Current Cardiac Medication 
The current cardiac medications will be collected al Baseline, while during the Follow-up Visits only 
the changes will be documented. 
 
NYHA Class Evaluation 
The patient´s New York Heart Association class will be assessed at Baseline and during all Follow-up 
visits. 
 
Implant Procedure Details 
Implant Procedure details (standard CRT-D implant) will be collected at Implant visit. 
 
Indicate model n°, serial n° and date of implant of entire implanted system (CRT-D device, Right 
Atrial (RA) lead, RV lead and LV lead). 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
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Final positions of all the implanted leads must be specified: right atrium, right ventricle and left 
ventricle lead positions. Additionally the final position of the LV poles will be collected.  
 
Fluoroscopy Images Collection (EDC upload) 
As  the  lead  placement  is  important  to  understanding  the  patient’s  response  to  CRT-D,  two 
Fluoroscopy images are requested to be collected: 
• LAO (Left Anterior Oblique, 45°±10°) (mandatory) 
• RAO (Right Anterior Oblique, 45°±10°) (mandatory) 
• AP (Anterior - Posterior) If available 
The position of all leads must be clearly visible to allow matching with the venous anatomy. These  
anonymized  images  should  be  uploaded  to  the  Electronic Data Capture (EDC) system . 
 
MPP Vector Test 
In order to allow future activation of MPP, specific LV pacing capture thresholds and Phrenic Nerve 
Stimulation (PNS) tests must be performed for the 4 cathodes during the implant. 
 
The test is considered positive in case is possible to identify at least 2 vectors from different Groups 
(with different Cathodes) with a Pacing Threshold that do not exceed 4.5V at 0.5ms pulse duration and 
without Phrenic Nerve Stimulation (PNS) at 1 Volt above the LV output. 
 
Conduction Delays Test 
The conduction delays between right and left ventricle will be performed during Implant and at 6 
Month follow up (with RV paced). This automatic test can be performed via Merlin PCS programmer 
and will end in about one minute.  
 
Device Interrogation and Programming 
Device will be interrogated and all the diagnostics retrieved. Standard sensing, pacing and impedance 
measurements will be performed for all implanted leads at implant and each in-clinic follow-up.   
 
The recommendation for the MPP programming in this study are (see Appendix E. Guidelines): 
 
MPP feature:  MPP feature will be TURNED ON in all patients with positive MPP Vector Test at 
implant. If the Investigator decides not to turn ON the MPP feature or there are not enough vectors 
available to activate this feature, the patient will be excluded from the study. 
 
MPP Cathode Selection: The pacing configuration will be chosen by the investigator following one of 
the 2 different approaches: 
• 
Electrical approach: choose the most electrically separated vectors based on the data provided 
by the Conduction Delay Test. 
• 
Anatomical approach: choose the most anatomically separated vectors based on the position 
of each pole, documented through fluoroscopic images. 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
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In this study, the Electrical approach is recommended. According the results of the Conduction Delays 
Test (with RV Paced) LV1 should be the one with the shortest conduction time, and LV2 the one with 
the longest conduction time. 
 
Pacing Vectors Selection: The anode of the pacing configuration will be chosen by the investigator 
based on the results of the capture threshold and PNS obtained in the MPP Vector Test. 
 
MPP delays programming: In this study the following general MPP programming is recommended: 
 
• 
MPP pacing sequence:  LV first: LV1 
D1→LV2 
D2 → RV 
• 
Timing Delays: use the minimum delays of 5 ms between LV1-LV2 and LV2-RV.  
 
MPP Capture Threshold Test: The simultaneous capture with both LV1 and LV2 vectors should be 
ensured. If the capture is not possible with the vectors selected, it is recommended changing one of the 
selected cathodes (LV1 or LV2) according investigator criteria and based on the electrical approach 
and the MPP Vector Test. The next steps should be repeated in order to check simultaneous capture 
with both LV1 and LV2 vectors.  
 
If simultaneous capture with both LV1 and LV2 vectors is not possible with electrical approach or the 
anatomical approach has been initially chosen, the same steps should be performed in order to check 
simultaneous capture with both LV1 and LV2 vectors.  
 
Alerts programming: It is recommended to activate the percentage of biventricular pacing Alert in 
Merlin.net. To activate this alert, it is necessary to activate it first in the device (using Programmer 
Merlin PCS). The aim of this alert is that the physician knows if the MPP feature is working properly 
or if it is necessary to set a date for an unscheduled follow-up to re-program the MPP feature. 
 
 
Echocardiography (Core Lab)  
Echocardiography images will be obtained according to the Echo Protocol at Baseline and 6 Month 
visit. They will be  submitted to an independent Echo Core Lab for central evaluation and assessment. 
 
The Baseline Echocardiography will be performed at any time after the patient signs the Patient 
Informed Consent, within 7 days before and 48 hours after the CRT-D implant procedure (with the 
CRT-D in No Pacing). The 6 Month Echocardiography will be performed during the 6 Month visit. 
 
The Echocardiography must be recorded in DICOM format and sent/uploaded to the Echo Core Lab 
within 72 hours (3 working days). The Core Lab will analyze the Baseline and the 6 Month 
Echocardiography and provide the evaluation of the CRT response based on the LVESV reduction. In 
addition, the following data will be analyzed and measured by the Core Lab: 
• LVEDD and LVESD 
• LVEDV and LVESV 
• LVEF 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
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• Mitral Insufficiency 
• Dyssynchrony measured by the strain rate (speckle tracking echocardiography) between the 
anteroseptal segment and the posterior wall (in patients which it is available) 
 
Substudy Echocardiography 
An additional Echocardiography will be obtained at the Substudy Visit according to the Echo Protocol. 
It will be recorded in DICOM and RAW file. This Echocardiography will not be sent/uploaded to the 
Echo Core Lab but evaluated locally at hospital. The following substudy data will be measured and 
collected at site: 
• Left Ventricular Outflow Tract (LVOT) diameter (although only one measure is mandatory, 3 
measurements are recommended) 
• Cardiac Output (CO) by Velocity Time Integral (VTI) value under 5 different pacing methods: 
o No Pacing  
o MPP using Electrical approach: choose the most electrically separated vectors (LV1 and 
LV2) based on the data provided by the Conduction Delay Test and the capture threshold 
and PNS obtained in the MPP Vector Test. 
o MPP using Anatomical approach: choose the most anatomically separated vectors (LV1 and 
LV2) based on the position of each pole (documented through fluoroscopic images) and the 
capture threshold and PNS obtained in the MPP Vector Test. 
o SPP: choose the vectors LV1 and LV2 of the approach (Electrical or Anatomical) with the 
best CO, and measure the data in:  
 SPP with LV1 
 SPP with LV2  
 
6.3 Enrollment Visit 
The Enrollment will be performed within 7 days before the Implant Procedure. The following 
enrollment activities are performed after the subject has been screened and must occur before any study 
procedure/visit. 
 
− The principal or delegated study personnel are responsible for screening all potential subjects 
to determine subject eligibility for the study. 
− If a patient meets all inclusion criteria and does not meet any of the exclusion criteria, he/she 
is eligible for the investigation. 
− Inform the eligible patient verbally about the investigation and provide the information sheet 
and consent form to the patient. 
− Provide ample time to the patient to read and understand the information sheet and consent 
form and to consider participation in the clinical investigation. 
− Obtain the signature and date from the eligible patient on the Ethics Committee (EC) 
approved informed consent form. 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
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− If an eligible patient does not sign and date the informed consent form, he cannot participate 
in the investigation. No further protocol required activities are performed. 
− Obtain the signature and date from the principal or delegated investigator on the EC approved 
consent form. 
− The subject is enrolled in the investigation when the patient signs the EC approved consent 
form. 
− Provide one original signed version of the informed consent form to the subject (signed by 
both subject and investigator) 
− File second original signed version of the informed consent form in the Investigator Site 
Binder (ISB). 
− Record enrollment information (name of the study, date of consent and Inclusion/exclusion 
information) in the hospital records and complete and submit the Enrollment form in a timely 
manner (recommended within 5 days)  
− Notification of enrollment to the sponsor will take place only when the sponsor receives the 
enrollment form  
 
NOTE: As soon as the subject signs the Patient Informed Consent, adverse events need to be reported 
according to the guidelines mentioned in section 8.2 
 
If a subject does not meet all inclusion criteria or meets any of the exclusion criteria, the subject cannot 
participate in the study and cannot be enrolled.  
 
In case the subject was already consented to participate in the study, but does not meet 
inclusion/exclusion criteria, the following actions will be taken: 
 
• Document 
enrollment 
information 
(name 
of 
the 
study, 
date 
of 
consent 
and 
inclusion/exclusion) in the hospital records; complete the Enrollment and Termination Forms. 
The forms must be authorized/approved by the principal or delegated investigator. 
• Inform the subject about the Termination. 
• Refer to Table 2: “Case Report Forms”. 
• Complete study deviation for inclusion/exclusion not met. 
• The Ethics Committee (EC) should be notify appropriately about any deviation with regards to 
obtaining the informed consent 
 
6.4 Baseline Visit (within 7 days of Enrollment) 
The clinical data collection of the Baseline Visit will be performed after patient signs the Patient 
Informed Consent and within 7 days after the Enrollment visit. The following information will be 
collected to describe patient’s clinical status: 
 
• Patient Data and Medical History 
• Current Cardiac Medication 
• NYHA Class Evaluation 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
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• Core Lab Echocardiography 
• Adverse Events and/or Hospitalization and/or Death and/or Protocol Deviation notification (if 
applicable) 
 
A Baseline Core Lab Echocardiography will be performed at any time after the patient signs the Patient 
Informed Consent, within 7 days before and 48 hours after the CRT-D implant procedure (with the 
CRT-D in No Pacing).  
 
The center must record the Echocardiography in DICOM format and send/provide it to the Core Lab 
within 72 hours (3 working days). The Core Lab will analyze the Echocardiography received and 
provide the evaluation of the measurements to St Jude Medical.  
 
6.5 Implant visit (within 7 days of Enrollment) 
The implant procedure of a SJM MPP compatible CRT-D system will be implanted with standard 
procedure within 7 days after the Enrollment. 
 
The Implant Procedures Details will be collected at the Implant section: 
• System information, model number, serial number and date of implant of entire implanted 
system (device, RA lead, RV lead and LV lead) 
• Leads position and LV lead poles position 
• Adverse Events and/or Hospitalization and/or Death and/or Protocol Deviation notification (if 
applicable) 
• Fluoroscopy Images collection (EDC upload) 
 
The following device tests will be collected at the Implant section: 
• MPP Vector Test 
• Conduction Delays Test 
• MPP programming (ON)  
• Final MPP configurations and method followed to decide it (Electrical delay approach or 
Anatomical approach) 
 
There are no specific procedures to be done for the substudy patients. 
 
6.6 Substudy Visit (within 7 days of the Implant)  
For the patients participating in the substudy a Hospital Echocardiography will be performed within 7 
days of the Implant procedure. Only patients in sinus rhythm in the moment of the Echocardiography 
can participate in this substudy. 
  
The substudy data detailed in Section 6.0 Hospital Echocardiography will be measured and collected 
at site. This Echocardiography will not be sent/uploaded to the Echo Core Lab 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
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6.7 Six Month Follow-up visit (In Clinic, 180 days +/- 30 days from device implant) 
The 6 Month Follow-up visit must be performed in-clinic within 180 +/- 30 days from the implant 
procedure. The purpose of the 6 Month Follow-Up visit is to check the patient’s and CRT-D 
system’s status as well as collect the necessary data to satisfy the study endpoints. 
 
The following information will be collected: 
• Current Cardiac Medication 
• NYHA Class evaluation 
• Echocardiography (Core Lab) 
• Device interrogation and Programming 
• Adverse Events and/or Hospitalization and/or Death and/or Protocol Deviation notification (if 
applicable) 
 
The center must record the Echocardiography in DICOM format and send/provide it to the Echo Core 
Lab within 72 hours (3 working days). The Core Lab will analyze the Echocardiography received and 
provide the evaluation of the measurements to St Jude Medical 
The Core Lab will be the responsible of classifying the patients as responders or non-responders 
according to the result of the analysis of the material provided.  
At the 6 Month visit the MPP programming will be according investigator´s discretion. 
 
There are no specific procedures to be done for the substudy patients. 
 
6.8 Unscheduled Visits (In Clinic)  
If there is any change in the MPP programming an Unscheduled Follow-up Form should be completed. 
No specific activity is forecasted for this visit, however the center should document all of the following 
whenever applicable: 
 
• Any changes in Current Cardiac Medication 
• Any changes in NYHA Class 
• MPP Vector Test  
• Conduction Delays Test (if available) 
• Any changes made to the MPP programming  
• Any Adverse Events and/or Hospitalization and/or Death and/or Protocol Deviation 
notification  
 
 
6.9 Description of activities performed by Sponsor Representatives 
Trained  sponsor  personnel  may  perform  certain  activities  to  ensure  compliance  to  the 
investigational plan and provide technical expertise. 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
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Sponsor personnel may: 
− Provide technical support to the Investigators during device tests and programming 
− Review medical charts to ensure accurate reporting of data in the electronic CRF (eCRF) 
 
Sponsor personnel will not: 
− Perform the informed consent process 
− Practice medicine 
− Provide medical diagnosis or treatment to subjects 
− Discuss  a  subject’s  condition  or  treatment  with  a  subject  without  the approval  and 
presence of a health care practitioner 
− Independently collect clinical investigational data 
− Complete or sign study’s Case report Forms 
 
 
6.10 Subject study completion 
When the subject’s participation in the clinical study has been completed which will be latest after the 
6 Months FU visit the subject will return to the medical care as per physician’s recommendation. 
 
6.11 Any Known or Foreseeable Factors that May Compromise the Outcome of the 
Clinical Study or the Interpretation of the Results 
All foreseeable factors that may compromise the outcome have been taken into account by clinical 
study design and well defined subject selection criteria. 
 
It is planned to enroll approximately 90 patients in the study from around 12 Spanish and/or Portuguese 
centers. The inclusion will be competitive and  there is not any enrollment target per center. 
It will be assured at the time of enrollment that the patients are able to follow the study schedule. 
Sponsor personnel will support the investigators and will ensure the completion of the Follow Ups. It is 
expected anyway a percentage of patients who will not complete the study procedures. This figure has 
been taken into account for the sample size calculation. 
 
The study may continue up to 2 years, dependent on the rate of enrollment.  
 
6.12 Criteria and Procedures for Subject Withdrawal or Discontinuation 
 
Subjects must be informed about their right to withdraw from the study at any time and for any reason 
without sanction, penalty or loss of benefits to which the subject is otherwise entitled and withdrawal 
from the study will not jeopardize their future medical care or relationship with the investigator. 
Subjects will be asked to specify the reason for the termination, but have the right not to answer. 
 
The investigator may decide to withdraw a subject from the study at any time with reasonable 
rationale. The subject’s future care will not be influenced by a decision, voluntary or otherwise, to 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
                                                                                                       Page 39 of 87  
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withdraw from the study. All reasonable efforts should be made to retain the subject in the clinical 
study until completion of the study. 
 
Reasons for subject’s withdrawal include, but are not limited to: 
 
• Subject refuses to continue participating in the study 
• Subject does not meet the inclusion/exclusion criteria and does not require additional follow-up 
for safety reasons. 
• Subject is deceased (cause must be documented) 
• Subject’s non-compliance 
• Subject’s participation is terminated by the PI or investigator, although the subject consented, 
since participation is no longer medically appropriate 
• Subject is ‘lost to follow up’: Subject does not adhere to the scheduled follow up visits but has 
not explicitly requested to be withdrawn from the clinical study. (This does not apply to missed 
visits). Site personnel should at all times make all reasonable efforts to locate and communicate 
with the subject in order to achieve subject compliance to the scheduled follow up visits: 
1.  A subject will be considered ‘Lost to Follow Up’ after a minimum of 2 phone calls of a 
physician or delegate at the investigational site to the subject or contact. These 2 phone calls 
need to be documented in the subject’s hospital records. 
2.  If these attempts are unsuccessful, a letter should be sent to the subject’s last known address 
or general practitioner (GP) and a copy of this letter should be maintained in the subject’s 
hospital records. 
 
Note: If a subject misses one or more of the scheduled follow up visits (inclusive of the assigned visit 
windows), this will be considered as a missed visit. The subject may therefore still return for 
subsequent visits and will not be excluded from the study. 
 
If a subject withdraws from the clinical study, the site will record the subject’s reasons for withdrawal, 
on a Termination CRF. 
 
When subject withdrawal from the clinical study is due to an adverse event the subject will be followed 
until resolution of that adverse event or determination that the subject’s condition is stable. The status 
of the subject’s condition should be documented at the time of withdrawal.   
 
 
7.0 COMPLIANCE TO CLINICAL INVESTIGATION PLAN (CIP) 
7.1 Statements of Compliance 
The study will be performed in accordance with the most current versions of the World Medical 
Association (WMA) Declaration of Helsinki, ISO14155:2011 and any regional and/or national 
regulations and will be compliant to this International Standard and any regional and national 
regulations, as appropriate. 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
                                                                                                       Page 40 of 87  
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The investigator will not start enrolling subjects or requesting informed consent from any subject prior 
to obtaining IRB/EC approval and Competent Authority approval, if applicable, and authorization 
from the sponsor in writing for the study. 
 
In case additional requirements are imposed by the IRB/EC or Competent Authority, those 
requirements will be followed, if appropriate. If any action is taken by an IRB/EC, and regulatory 
requirements with respect to the study, that information will be forwarded to St. Jude Medical. 
 
As sponsor, St. Jude Medical has taken up general liability insurance in accordance with the 
requirements of the applicable local laws. Appropriate country representative will be utilized to 
understand the requirements for the type of insurance that will be provided for subjects, such 
information will be incorporated into the informed consent, as applicable 
 
If required, additional subject coverage or a study specific insurance will be provided by the Sponsor as 
well. 
 
7.2 Adherence to the Clinical Investigation Plan 
A deviation is defined as an event where the clinical investigator, site personnel, sponsor or sponsor 
representative did not conduct the clinical study according to the Clinical Investigational Plan, IRB/EC 
requirements or the Investigator Agreement. The investigator is not allowed to deviate from the CIP, 
except as specified under emergency circumstances.   
 
In some cases, failure to comply with the CIP may be considered failure to protect the rights, safety and 
well-being of subjects, since the non-compliance exposes subjects to unreasonable risks. For example, 
failure to adhere to the inclusion/exclusion criteria: these criteria are specifically defined by the 
Sponsor to exclude subjects for whom the device is not beneficial and the use involves unreasonable 
risks. This may be considered failure to protect the rights, safety and well-being of the enrolled subject. 
Similarly, failure to perform safety assessments intended to detect adverse events may be considered 
failure to protect the rights, safety and well-being of the enrolled subject. Investigators should seek 
minimization of such risks by adhering to the CIP. 
 
Simultaneously, in the event that adhering to the CIP might expose the subject to unreasonable risks, 
the investigator is also required to protect the rights, safety and well-being of the subject by 
intentionally deviating from the requirements of the CIP, so that subjects are not exposed to 
unreasonable risks.  
 
It is the responsibility of the investigator to provide adequate medical care to a subject enrolled in a 
study. 
 
Regulations require that the PI maintain accurate, complete, and current records, including documents 
showing the date of and reason for every deviation from the Clinical Investigational Plan.  Relevant 
information for each deviation will be documented on a Protocol Deviation Case Report Form. The site 
will submit the CRF to St. Jude Medical. 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
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Regulations require Investigators obtain approval from St. Jude Medical and the IRB/EC [as required] 
before initiating changes in or deviations from the protocol, except when necessary to protect the life or 
physical well-being of a subject in an emergency. Under emergency circumstances, deviations from the 
CIP to protect the rights, safety and well-being of human subjects may proceed without prior approval 
of the sponsor and the EC. Such deviations shall be documented and reported to the sponsor and the 
EC as soon as possible, but no later than 5 working days   
 
Prior approval must be requested when the PI anticipates, contemplates, or makes a conscious decision 
to depart from the CIP, except when unforeseen circumstances are beyond the investigator’s control 
(e.g. a subject who fails to attend a scheduled follow-up visit, a subject is too ill to perform a CIP-
required test, etc.).  All deviations, including those beyond the investigator’s control, must be reported 
on a CRF. 
 
To obtain approval, the Principal Investigator may call or email and discuss the potential deviation with 
St. Jude Medical or designee prior to initiating any changes.   
 
Investigators or the designee must notify St. Jude Medical of any protocol deviation as soon as possible 
and complete the Protocol Deviation CRF. All deviations must be reported to appropriate regulatory 
authorities according to the local regulation (as appropriate). 
 
 
7.3 Repeated and serious non-compliance 
In the event of repeated non-compliance or a one-time serious non-compliance, as determined by the 
Sponsor, a Clinical Research Associate or clinical representative will attempt to secure compliance by 
one or more of the following actions: 
• Visiting the investigator 
• Contacting the investigator by telephone 
• Contacting the investigator in writing 
• Retraining of the investigator 
 
If an investigator is found to be repeatedly non-compliant with the signed agreement, the CIP or any 
other conditions of the clinical study, the Sponsor will either secure compliance or, at its sole 
discretion, terminate the investigator’s participation in the clinical study. 
 
8.0 ADVERSE EVENT, ADVERSE DEVICE EFFECT 
8.1 Definitions 
8.1.1 Medical device 
Any instrument, apparatus, implement, machine, appliance, implant, software, material or other similar 
or related article 

Study Document No: SJM-CIP-10058 
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Study Name: QUARTO III study 
CIP  
 
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• Intended by the manufacturer to be used, alone or in combination, for human beings for one or 
more of the specific purpose(s) of 
o Diagnosis, prevention, monitoring, treatments or alleviation of disease, 
o Diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury, 
o Investigation, replacement, modification, or support of the anatomy or of a physiological 
process, 
o Supporting or sustaining life, 
o Control of conception, 
o Disinfection of medical devices and 
• Which does not achieve its primary intended action in or on the human body by pharmacological, 
immunological or metabolic means, but which may be assisted in its intended function by such 
means 
 
8.1.2 Adverse Event (AE) 
Any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including 
abnormal laboratory findings) in subjects, users or other persons, whether or not related to the 
investigational medical device under study. 
 
This definition includes events related to the investigational medical device. 
This definition includes events related to the procedures involved. 
 
8.1.3 Serious Adverse Event (SAE) 
An adverse event that led to: 
• Death 
• A serious deterioration in the health of the subject, that either resulted in: 
o A life-threatening illness or injury OR 
o A permanent impairment to a body structure or a body function OR 
o An in-patient or prolonged hospitalization OR 
o A medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to a body structure or a body OR 
o A malignant tumor 
• Fetal distress, fetal death or a congenital abnormality or birth defect 
 
A planned hospitalization for a pre-existing condition, or a procedure required by the CIP is not 
considered a serious adverse event.  
 
 
8.1.4 Adverse Device Effect (ADE) 
An adverse event related to the use of an investigational medical device. 

Study Document No: SJM-CIP-10058 
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This definition includes adverse events resulting from insufficient or inadequate instructions for use, 
deployment, implantation, installation, or operation, or any malfunction of the investigational medical 
device. 
 
This definition includes any event resulting from the use error or from intentional misuse of the 
investigational medical device. 
 
8.1.5 Serious Adverse Device Effect (SADE) 
Adverse device effect that has resulted in any of the consequences characteristic of a serious adverse 
event. 
 
8.1.5.1 Unanticipated Serious Adverse Device Effect (USADE)  
A serious adverse device effect which by its nature, incidence, severity or outcome has not been 
identified in the current version of the risk analysis report. 
 
8.1.5.2 Anticipated Serious Adverse Device Effect (ASADE)  
A serious adverse device effect which by its nature, incidence, severity or outcome has been previously 
identified in the risk analysis report. 
 
8.2 Procedure for assessing, recording and reporting adverse events, adverse device effects, 
serious adverse events and serious adverse device effects:  
Safety surveillance within this study and the safety reporting both performed by the investigator, starts 
as soon as the subject is enrolled in this study (date of signature of the informed consent). The safety 
surveillance and the safety reporting will continue until the last investigational visit has been 
performed, the subject is deceased, the subject/investigator concludes his participation into the study or 
the subject/investigator withdraws the subject from the study, except as otherwise specified in the CIP. 
 
All adverse event data including deaths will be collected throughout the clinical study and will be 
reported to the Sponsor through the EDC system. The Investigator will record all adverse events and 
device deficiencies on the appropriate case report forms.  
 
Records relating to the subject’s subsequent medical course must be maintained and submitted (as 
applicable) to the Sponsor until the event has subsided or, in case of permanent impairment, until the 
event stabilizes and the overall clinical outcome has been ascertained. Adverse events will be 
monitored until they are adequately resolved.  The status of the subject’s condition should be 
documented at each visit.   
 
The investigator will report the event to the IRB/EC per their reporting requirements.  
 

Study Document No: SJM-CIP-10058 
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Study Name: QUARTO III study 
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Reportable events to sponsor are considered:  
• 
All Serious Adverse Events including Serious Adverse Device Effect and all Adverse Device 
Effects are to be documented and reported to the sponsor maximum 24 hours after becoming 
aware of the event 
• 
Non-Serious Adverse Events documentation and reporting are limited to cardiovascular events. 
Non-serious events are to be reported as soon as possible but not later than 2 weeks after 
becoming aware 
 
The Sponsor will ensure that all events and device deficiencies are reported to the relevant authorities 
as per regulations.  
 
In case of EDC failure, notify Sponsor via AdverseEvent@sjm.com or via Fax (please refer to the 
Investigator Site Binder, section “Sponsor Contact Details” for further details about Fax numbers). 
 
Additional information may be requested, when required, by the Sponsor in order to support the 
reporting of AEs to regulatory authorities. 
 
The investigator must notify the IRB/EC, if appropriate, in accordance with national and local laws and 
regulations, of the AEs reported to the Sponsor. 
 
All adverse events will be reported as per applicable regulatory requirements.  
 
8.3 Subject Death 
8.3.1 Procedure for recording and reporting subject death 
 
All subject deaths are to be documented and reported to the sponsor within 24 hours after becoming 
aware of the event. 
 
The timing of the Death will be classified as:  
• 
Pre-procedure Death (before the Implant/procedure)  
• 
Peri-Procedure Death (within <=30 days of the implant/procedure) 
• 
Post-Procedure Death (within >30 days after implant/procedure) 
 
Should death occur, the investigator is requested to record death information in the hospital records and 
immediately document the information on the Death form. By completing the form the sponsor will be 
notified. 
In case of EDC failure, notify Sponsor via AdverseEvent@sjm.com or via Fax (please refer to the 
Investigator Site Binder, section “Sponsor Contact Details” for further details about Fax numbers). 
 
Patient Death can be an outcome of a serious adverse event (SAE) or serious adverse device effect 
(SADE). 

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• Death is therefore related to an SAE/SADE: all efforts to obtain the SAE/SADE details should be 
made and the Adverse Event form must be completed 
• The patient’s death is an Early Conclusion of the subject’s participation in the investigation. 
Therefore, the investigator is requested to complete the Termination form 
• The investigator must notify the EC / IRB, if appropriate, in accordance with national and local 
laws and regulations 
 
 
9.0 DATA MANAGEMENT 
Overall, the Sponsor will be responsible for the data handling. 
 
The sponsor and/or its affiliates will be responsible for compiling and submitting all required reports to 
governmental agencies. 
 
Data will be analyzed by the Sponsor and may be transferred to the Sponsor’s locations outside of 
Europe and/or any other worldwide regulatory authority in support of a market-approval application. 
 
St. Jude Medical respects and protects personally identifiable information that we collect or maintain. 
As part of our commitment, St. Jude Medical is certified to the U.S. - European Union Framework and 
U.S. – Swiss Safe Harbor Framework Agreements regarding human resources and subject clinical trial 
personal information. The privacy of each subject and confidentiality of his/her information will be 
preserved in reports and when publishing any data. Confidentiality of data will be observed by all 
parties involved at all times throughout the clinical study. All data will be secured against unauthorized 
access. 
 
The Principal Investigator or institution will provide direct access to source data during and after the 
clinical study for monitoring, audits, IRB/EC review and regulatory authority inspections.  As required, 
the Principal Investigator or institution will obtain permission for direct access to source documents 
from the subject, hospital administration and national regulatory authorities before starting the clinical 
study. 
 
9.1 Data Management Plan 
A detailed Data Management Plan (DMP) will be established to ensure consistency of the data. This 
document will include procedures used for data review, database cleaning, and issuing and resolving 
data queries. If appropriate, the DMP may be updated throughout the study duration. All revisions will 
be tracked and document controlled. 
 
CRF data will be captured in a validated electronic database management system hosted by St. Jude 
Medical.  
 

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without the express written consent of St. Jude Medical  
 
Only authorized site personnel will be permitted to enter the CRF data through the electronic data 
capture (EDC) system deployed by St. Jude Medical. An electronic audit trail will be used to track any 
subsequent changes of the entered data. 
 
 
9.2 Document and data control 
9.2.1 Traceability of documents and data 
The investigator will ensure accuracy, completeness, legibility and timeliness of the data reported to 
the sponsor on the CRFs and in all required reports.  
 
9.2.2 Recording data 
Source documents will be created and maintained by the investigational site team throughout the 
clinical study. 
 
The data reported on the CRFs will be derived from, and be consistent with, these source documents, 
and any discrepancies will be explained in writing. 
 
The CRFs shall be validated by the principal investigator or delegated site personnel as specified on the 
Signature and Delegation Log. In case of modifications after the validation, the eCRFs should be re-
approved. 
 
10.0 MONITORING  
It is the responsibility of St. Jude Medical as the sponsor of the study to ensure the study is conducted, 
recorded, and reported according to the approved protocol, subsequent amendment(s), applicable 
regulations, and guidance documents. Monitoring will be conducted according to the St. Jude Medical 
Clinical Monitoring standard operating procedure. 
 
Prior to beginning the study, St. Jude Medical will contact the investigator or designee to discuss the 
study and data requirements. A St. Jude Medical monitor will periodically review the subject records 
and associated source documents.  
 
The investigator shall make subject and study records available to the clinical monitor for monitoring.   
Centralized monitoring will occur through routine internal data review.  This monitoring is designed to 
identify missing and inconsistent data, data outliers, and potential protocol deviations that may be 
indicative of site non-compliance.  
 

Study Document No: SJM-CIP-10058 
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Study Name: QUARTO III study 
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11.0 REGULATORY INSPECTIONS 
The investigator and/or delegate should contact St. Jude Medical immediately upon notification of a 
governmental agency inspection at the site. A clinical monitor or designee will assist the investigator 
and/or delegate in preparing for the audit. 
 
An investigator who has authority to grant access will permit authorized governmental agency 
employees, at reasonable times and in reasonable manner, to enter and inspect any establishment 
where devices are held (including any establishment where devices are used or where records or results 
are kept). 
 
An investigator, or any person acting on behalf of such a person with respect to the study, will permit 
authorized governmental agency employees, at reasonable times and in reasonable manner, to inspect 
and copy all records relating to the study. 
 
An investigator will permit authorized governmental agency employees to inspect and copy records 
that identify subjects, upon notice that governmental agency has reason to suspect that adequate 
informed consent was not obtained, or that reports required to be submitted by the investigator, to the 
Sponsor or IRB/EC have not been submitted or are incomplete, inaccurate, false or misleading. 
 
12.0 STATISTICAL CONSIDERATIONS 
12.1 Statistical design, hypotheses, method and analytical procedures 
The primary endpoint analysis will be based on the intention-to-treat (ITT) principle including all 
protocol deviatons. Secondary per-protocol (PP) analysis excluding all major protocol deviators will 
also be conducted. If the results obtained from these analyses are different, an exploration of the data to 
search for the reason will be performed. 
For the primary endpoint analysis, the following inequality hypothesis will be tested: 
• H0: Proportion of responders at 6 months with the MPP feature activated at baseline ≤ 57%  
• H1: Proportion of responders at 6 months with the MPP feature activated at baseline > 57% 
 
All results will be expressed in terms of 97.5% corresponding confidence intervals and p-values. P-
values less than 2.5% will be considered significant. 
  
12.2 Sample size 
The sample size calculation is based on the primary endpoint, proportion of CRT responders at 6 
months who have the MPP feature activated at baseline. 
Using a one-sided one sample Exact Binomial Test, a significance level of 2.5%, a total of 74 patients 
is needed to reach a power of 90%. 
With the MPP feature activated at baseline, it is assumed that the proportion of responders at 6 months 
will be 75%. The MPP responder rate will be compared to 57%, which is the responder rate obtained 
from literature [28] for patients without the MPP feature activated. 

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without the express written consent of St. Jude Medical  
 
In order to detect the 18% difference between the two responder rates, a total of 74 patients need to 
have analyzable endpoint data at 6 months.  
From clinical experience, it is assumed that some patients will drop out of the study (5% during the 
first 6 months of implantation, 5% due to implant failure and 8% due to MPP activation failure). In 
order to account for these dropout rates, a total of 90 patients will be recruited.  
  
12.3 Statistical hypotheses, method and analytical procedures for Sub-study endpoint 
There is no formal sample size estimation for the sub-study endpoint. The sub-study endpoint data will 
be reported using frequencies and percentages.  
An exploratory one-sided one sample exact binomial test may be performed to compare the proportion 
of patients who achieve a greater hemodynamic with the MPP feature to 53%, which is the responder 
rate obtained from literature [27]for patients with traditional SPP. 
For this exploratory analysis, the following inequality hypothesis will be tested: 
• H0: Proportion of patients who achieve a greater hemodynamic response, measured by Cardiac 
Output, with a MPP configuration within 7 days after implant ≤ 53%  
• H1: Proportion of patients who achieve a greater hemodynamic response, measured by Cardiac 
Output, with a MPP configuration within 7 days after implant > 53% 
P-values less than 5% will be considered significant.  Corresponding 95% confidence interval will also 
be reported. Interim reporting of the sub-study endpoint data will be performed when the required data 
have been collected from all the sub-study patients. 
 
12.4 Pass/fail criteria to be applied to the results of the clinical study 
Not applicable. 
 
12.5 The provision for an interim analysis, when applicable 
Not applicable. 
 
12.6 Criteria for the termination of the clinical study on statistical grounds 
Not applicable. 
 
12.7 Procedures for reporting any deviation(s) from the original statistical plan 
Any deviations from the Statistical analysis plan will be documented in a note to file 
 

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Study Name: QUARTO III study 
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without the express written consent of St. Jude Medical  
 
12.8 The specification of subgroups for analysis 
Subgroup analysis will be performed for Ischemic and non-ischemic patients. 
 
12.9 Procedures that take into account all the data 
Primary endpoint analysis will take into account all available data. 
 
12.10 The treatment of missing, unused or spurious data, including drop-outs and 
withdrawals 
No imputation techniques will be used for missing data. 
 
12.11 The exclusion of particular information for the testing of the hypothesis, if relevant, 
and  
Not applicable. 
 
12.12 In multi-center studies, the minimum and maximum number of subjects to be 
included for each center 
There is no minimum or maximum for the number of patients to be enrolled for each center. 
 
13.0 DOCUMENT RETENTION 
The principal investigator will maintain all clinical study documents from prior, during and (as 
specified) after the clinical study on file at the site for a minimum of 15 years after the termination of 
this study, or longer as per local laws, or when it is no longer needed to support a marketing 
application, whichever is later.   
The PI must contact the sponsor prior to destroying or archiving off-site any records and reports 
pertaining to this study to ensure that they no longer need to be retained on-site. 
All original subject files must be stored for the longest possible time permitted by the regulations at the 
hospital, research institute, or practice in question. If archiving can no longer be maintained at the site, 
the investigator will notify the sponsor.  
 
All data and documents will be made available on request of the relevant authorities in case of an audit. 
 
The sponsor will archive and retain all essential clinical study documents from prior, during and (as 
specified) after the clinical study as per requirements.  
 

Study Document No: SJM-CIP-10058 
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Study Name: QUARTO III study 
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without the express written consent of St. Jude Medical  
 
14.0 AMENDMENTS TO CLINICAL INVESTIGATIONAL PLAN 
Study related documents such as, the Investigator Brochure (IB), Report of Prior Investigations (RPI) 
CIP, CRFs, Informed Consent form and other subject information, or other clinical study documents 
will be amended as needed throughout the clinical study, and a justification statement will be included 
with each amended section of a document. Proposed amendments to the CIP will be agreed upon 
between the Sponsor and the coordinating investigator (if applicable).  
 
The amendments to the CIP and the subject’s Informed Consent will be notified to, or approved by, the 
IRB/EC and regulatory authorities, if required. The version number and date of amendments will be 
documented. 
 
The amendment will identify the changes made, the reason for the changes and if it is mandatory or 
optional to implement the amendment. 
 
Any amendment affecting the subject requires that the subject be informed of the changes and a new 
consent be signed and dated by the investigator at the subject’s next follow up. 
 
Changes to, or formal clarifications of, the CIP will be documented in writing and provided to the 
investigators. This information will be incorporated when an amendment occurs. 
 
15.0 OUTSOURCING OF DUTIES AND FUNCTIONS  
The sponsor may transfer any or all of the duties and functions related to the clinical study, including 
monitoring, to an external organization (such as a Clinical Research Organization (CRO) or individual 
contractor), but the ultimate responsibility for the quality and integrity of the clinical study will reside 
with the sponsor. All requirements applying to the sponsor will also apply to the external organization 
inasmuch as this organization assumes the clinical study related duties and functions of the sponsor. 
 
15.1 Echocardiography Core Lab 
Service details are outlined in the Service Agreement, and can be provided upon request. 
 
16.0 INVESTIGATION SUSPENSION OR TERMINATION 
16.1 Premature termination of the whole clinical study or of the clinical study in one or 
more investigational sites. 
The Sponsor reserves the right to stop the study at any stage, with appropriate written notice to the 
investigator.  
 
Possible reasons for early termination of the study by the sponsor, either at local, national or 
international level, may include, but are not limited to: 
 
• The device /  therapy fails to perform as intended 

Study Document No: SJM-CIP-10058 
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• Occurrence of USADE which cannot be prevented in future cases 
• Sponsor’s decision 
• Recommendation from Data Safety Monitoring Board (DSMB) to Steering committee and 
Sponsor 
• Request from Regulatory bodies 
• Request of Ethics Committee(s)  
• Concern for subject safety and welfare 
• Failure to secure subject Informed Consent prior to any investigational activity 
• Failure to report unanticipated adverse device effects within 24 hours to St. Jude Medical and the 
EC 
• Repeated non-compliance with this CIP or the Clinical Trial Agreement 
• Inability to successfully implement this CIP 
• Violation of the Declaration of Helsinki 2013 (refer to Appendix C: Declaration of Helsinki) 
• Violation of applicable national or local laws and regulations 
• Falsification of data, or any other breach of ethics or scientific principles 
• Loss of or unaccounted use of investigational device inventory 
 
The study will be terminated according to applicable regulations. 
 
The investigator may also discontinue participation in the clinical study with appropriate written notice 
to the Sponsor. 
 
Should either of these events occur, the investigator will return all documents to the sponsor; provide a 
written statement as to why the premature termination has taken place and notify the IRB/EC and/or 
the Competent Authority (if applicable). Follow-up for all enrolled subjects will be as per CIP 
requirements. 
 
A Principal Investigator, IRB/EC or regulatory authority may suspend or prematurely terminate 
participation in a clinical study at the investigational sites for which they are responsible.   
 
If suspicion of an unacceptable risk to subjects arises during the clinical study or when so instructed by 
the IRB/EC or regulatory authority, St. Jude Medical may suspend the clinical study as appropriate 
while the risk is assessed.  St. Jude Medical will terminate the clinical study if an unacceptable risk is 
confirmed.   
 
St. Jude Medical will consider terminating or suspending the participation of a particular 
investigational site or investigator in the clinical study if monitoring or auditing identifies serious or 
repeated deviations on the part of an investigator.   
 
If suspension or premature termination occurs, the terminating party will justify its decision in writing 
and promptly inform the other parties with whom they are in direct communication.  The Principal 
Investigator and St. Jude Medical will keep each other informed of any communication received from 
IRB/EC or regulatory authority.   

Study Document No: SJM-CIP-10058 
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without the express written consent of St. Jude Medical  
 
 
If for any reason St. Jude Medical suspends or prematurely terminates the study at an individual 
investigational site, St. Jude Medical will inform the responsible regulatory authority, as appropriate, 
and ensure that the IRB/EC are notified, either by the Principal Investigator or by St. Jude Medical.  If 
the suspension or premature termination was in the interest of safety, St. Jude Medical will inform all 
other Principal Investigators.   
 
If suspension or premature termination occurs, St. Jude Medical will remain responsible for providing 
resources to fulfill the obligations from the CIP and existing agreements for following up the subjects 
enrolled in the clinical study, and the Principal Investigator or authorized designee will promptly 
inform the enrolled subjects at his/her investigational site, if appropriate.   
 
 
16.2 Resuming the study after temporary suspension 
When St. Jude Medical concludes an analysis of the reasons for the suspension, implements the 
necessary corrective actions, and decides to lift the temporary suspension, St. Jude Medical will inform 
the Principal Investigators, IRB/EC, or regulatory authority, where appropriate, of the rationale, 
providing them with the relevant data supporting this decision.   
 
Concurrence will be obtained before the clinical study resumes from the IRB/EC or regulatory 
authority where appropriate.   
 
If subjects have been informed of the suspension, the Principal Investigator or authorized designee will 
inform them of the reasons for resumption. 
 
16.3 Study conclusion 
The study will be concluded when: 
• All sites are closed AND 
• The Final report generated by St. Jude Medical has been provided to sites or St. Jude Medical has 
provided formal documentation of study closure 
 
17.0 PUBLICATION POLICY 
The results of the clinical study will be submitted, whether positive or negative for publication.  
 
A ‘Publication Agreement’ will be signed between the Principal Investigator and the Sponsor either as 
a separate Publication Agreement or within the Clinical Trial Agreement. 
 
For more information on publication guidelines, please refer to the International Committee of Medical 
Journal Editors (ICMJE) on www.icmje.org. 
 
This study will be posted on ClinicalTrials.gov and results will be posted on ClinicalTrials.gov as 
required.  

Study Document No: SJM-CIP-10058 
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Study Name: QUARTO III study 
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without the express written consent of St. Jude Medical  
 
 
 
18.0 BIBLIOGRAPHY 
 
[1]  "Task Force for Diagnosis and Treatment of Acute and Chronic Heart Failure. ESC Guidlines for the Diagnosis and 
Treatment of Acute and Chronic Heart Failure 2012," European Heart Journal. Doi: 10.1093/eurheartj/ehs104.  
[2]  Dickstein K, Cohen-Soal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, Stromberg A, Van 
Veldhuisen DJ, Atar D, Hoes AW, Keren A, Mebazaa A, Nieminen M, Priori SG and Swedberg K, "ESC guidelines 
for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment 
of acute and chronic heart failure 2008 of Europear Society of Cardilogy," Developed in collaboration with the Heart 
Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESCIM). 
Eur J Heart Fail 2008; 10:933-989.  
[3]  Davie AP, Francis CM, Caruana L, Sutherland GR and McMurray JJ, "Assessing diagnosis in heart failure: which 
features are any use?," QJM 1997;90:335-339.  
[4]  Mant J, Doust J, Roalfe A, Barton P, Cowie MR, Glasziou P, Mant D, McManus RJ, Holder R, Deeks J, Fletcher K, 
Qume M, Sohanpal S, Sanders S and Hobbs FD, "Systematic review and individual patient data meta-analysis of 
diagnosis of heart failure with modelling of implications of different diagnostic strategies in primary care," Health 
Technol Assess 2009;13:1-207,iii.  
[5]  Oudejans I, Mosterd A, Bloemen JA, Valk MJ, van Velzen E, Wielders JP, Zuithoff NP, Rutten FH and Hoes AW, 
"Clinical evaluation of geriatric outpatients with suspected heart failure: value of symptoms, signs and additional test," 
Eur J Heart Fail 201 (1) 1;13:518-527.  
[6]  Fonseca C, "Diagnosis of heart failure in primary care," Heart Fail Rev 2006:11:95-107.  
[7]  Kelder JC, Cramer MJ, van Wijngaarden J, van Tooren R, Mosterd A, Moons KG, Lammers JW, Cowie MR, Grobbee 
DE and Hoes AW, "The diagnostic value of physical examination and additional testing in primary care patients with 
suspected heart failure," Circulation 2011;124:2865-2873.  
[8]  Farwell D, Patel NR, Hall A, Ralph S and Sulke AN, "How many people with heart failure are appropriate for 
biventricular resynchronization?," Eur Heart J 2000;21(15):1246-50.  
[9]  Hare JM, "Cardiac-resynchronization therapy for heart failure," N Engl J Med 2002;346(24):1902-5.  
[10] Liu P, Arnold M, Belenkie I and et al, "The 2001 Canadian Cardiovascular Society consensus guideline update for the 
management and prevention of heart failure," Can J Cardiol 2001:17Suppl E:5E-25E.  
[11] Liu P, Arnold JM, Belenkie I and et al, "The 2002/3 Canadian Cardiovascular Society consensus guideline update for 
the diagnosis an management of heart failure," Can J Cardiol 2003;19(4):347-56.  
[12] Tsuyuki RT, Shibata MC, Nilsson C and Hervas-Malo M, "Contemporary burden of illness of congestive heart failure 
in Canada," Can J Cardiol 2003;19(4):436-8.  
[13] Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G and et al, "Executive summary:Heart 
disease and stroke statistics 2010 update: A report from the American Heart Association," Circulation 2010; 121:948-
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[14] Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Carnethon MR, Dai S, de Simone G, Ford ES, 
Fox CS, Fullerton HJ, Gillespie C, Greenlund KJ, Hailpern SM, Heit JA, Ho PM, Howard VJ, Kissela BM, Kittner SJ, 
Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, McDermott MM, Meigs 
JB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Rosamond WD, Sorlie PD, Stafford RS, Turan 
TN, Turner MB, Wong ND and Wylie-Rosett J, "Heart disease and stroke statistics 2011 update: A report from the 
american heart association," Circulation 2011; 123;e18-e209.  
[15] Abraham WT, Fisher WG, Smith AL and et al, "Cardiac resynchronization in chronic heart failure," N Engl J Med 
2002;346(24):1845-53.  
[16] Auricchio A, Ding J, Spinelli JC and et al, "Cardiac resynchronization therapy restores optimal atrioventricular 

Study Document No: SJM-CIP-10058 
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Study Name: QUARTO III study 
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mechanical timing in heart failure patients with ventricular conduction delay," J Am Coll Cardiol 2002; 39(7):1163-9.  
[17] Stellbrink C, Auricchio A, Butter C and et al, "Pacing therapies in congestive heart failure II study," Am J Cardiol 
2000;86(9Suppl 1):K138-K43.  
[18] Stellbrink C, Breithardt OA, Franke A and et al, "Impact of cardiac resynchronization therapy using hemodynamically 
optimized pacing on left ventricular remodeling in patients with congestive heart failure and ventricular conduction 
disturbances (1)," J Am Coll Cardiol 2001;38(7):1957-65.  
[19] St John Sutton MG, Plappert T, Abraham WT and et al, "Effect of cardiac resynchronization therapy on left ventricular 
size and function in chronic heart failure," Circulation 2003;107(15):1985-90.  
[20] Strickberger SA, Conti J, Daoud EG and et al, "Patient selection for cardiac resynchronization therapy:from the 
Council on Clinical Cardiology Subcommittee on Electrocardiography and Arrhythmias and the Quality of Care and 
Outcomes Research Interdisciplinary Working Group,in collaboration with the HRS," Circulation 2005;111(16):2146-
50.  
[21] Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, Kocovic DZ, Packer M, Clavell AL, Hayes DL, 
Ellestad M, Trupp RJ, Underwood J, Pickering F, Truex C, McAtee P and Messenger J, "Cardiac resynchronization in 
chronic heart failure," N Engl J Med 2002; 346:1845-1853.  
[22] Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L and Tavazzi L, "The effect of cardiac 
resynchronization on morbidity and mortality in heart failure," N Engl J Med 2005;352:1539-1549.  
[23] Salukhe TV, Francis DP and Sutton R, "Comparison of medical therapy, pacing and defibrillation in heart failure 
(companion)trial terminated early;combined biventricular pacemaker-defibrillators reduce all-cause mortality and 
hospitalization," International journal of cardiology 2003;87:119-120.  
[24] Pires LA, Abraham WT, Young JB and Johnson KM, "Clinical predictors and timing of new york heart association 
class improvement with cardiac resynchronization therapy in patients with advanced chronic heart failure. Results from 
the multicenter insync randomized clinical evaluation (miracle) and....," Am Heart J 2006;151:837-843.  
[25] Birnie DH and Tang AS, "The problem of non-response to cardiac resynchronization therapy," Curr Opin Cardiol 
2006;21:20-26.  
[26] J. Toquero Ramos, L. Ruiz Bautista, P. Beltrán Correas, J. M. Fernández Villanueva, V. Castro Urda, A. Restrepo 
Cordoba, J. Goirigolzarri Artaza , I. Fernández Lozano, A. Ruiz Jurado and S. Alyoun Alonso, "Estimulación 
Multipunto mediante Captura Anódica VI a través de un Electrodo Cuadripolar: Evaluacion Hemodinámica no 
Invasiva," Rev Esp Cardiol. , vol. 67 Supl1:405, no. 6004-65, 2014.  
[27] F. J. Cabrera-Bueno, J. Olagüe Ros, I. Fernández-Lozano, J. J. García Guerrero , J. Fernández de la Concha, A. 
Hernández-Madrid, J. M. Tolosana Viu, A. Barrera Cordero , J. Osca Asensi, V. Moñivas Palomero, A. Ruiz Jurado, 
E. Llorente Hernangómez and J. Alzueta Rodríguez, "Improvement in Hemodynamic Response Using a New 
Quadripolar LV Lead," Europace, vol. 14 Suppl.1 June 2012, no. Abstract 176P-25, p. i60, 2012.  
[28] Pappone C. et al., "Multipoint Left Ventricular Pacing in a Single Coronary Sinus Branch Improves Mid-Term 
Echocardiography and Clinical Response to Cardiac Resynchronization," Journal of Cardiovascular 
Electrophysiology. 2014 Aug 11.Doi:10.1111/jce.12513.  
[29] Gutleben et al, "Multisite Left Ventricular Pacing is Safe and Improves Cardiac Hemodynamic in Heart Failure 
Patients-Results from a 1 month Follow-up Study," abstract HRS 2012.  
[30] Papone C., et al, "Improvement in 3-month echocardiographic response with multisite left ventricular pacing in cardiac 
resynchronization therapy patients," HRS 2013 Poster session PO02. May 9,2013.  
[31] Thibault et al, "Multisite Pacing with a Quadripolar Left Ventricular Lead Improves Acute Hemodynamics," Abstract 
HRS 2011.  
[32] Papone C., et al, "Multisite left ventricular pacing in a single coronary sinus branch improves systolic and diastolic 
acute hemodynamic response assessed with pressure-volume loops," Abstract HRS 2013.  
[33] Papone C., et al, "Left ventricular pacing from a site of late electrical activation improves acute hemodynamics in CRT 
patients implanted with a quadripolar left ventricular lead," Abstract HRS 2013.  
[34] Thibault B, Dubuc M, Khairy P, Guerra PG, Macle L, Rivard L, Roy D, Talajic M, Karst E, Ryu K, Paiement P and 

Study Document No: SJM-CIP-10058 
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Farazi TG, "Acute haemodynamic comparison of multisite and biventricular pacing with a quadripolar left ventricular 
lead," Europace. 2013 Jul;15(7):984-91.  
[35] Rinaldi et al, "Acute hemodynamic benefits of multisite left ventricular pacing in CRT recipients," Abstract ACC 2012. 
[36] Rinaldi et al, "Multisite left ventricular pacing improves acute mechanical dyssynchrony in heart failure patients," 
Abstract ACC 2012.  
 
 
 
 

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APPENDIX A: ABBREVIATIONS 
 
Select or add abbreviations used 
Abbreviation 
Term 
ADE 
AE 
AF 
ASADE 
AV 
BiV 
CABG 
CO 
CIP 
CRF 
CRT-D 
DMP 
EC 
Echo 
eCRF 
EDC 
EF 
HF 
ICD 
IRB 
ISO 
LV 
LVEDD 
LVEDV 
LVEF 
LVESD 
LVESV 
LVOT 
 MPP 
NYHA 
PCS  
PI 
PM 
PNS 
PTCA 
RA 
RV 
SADE 
SAE 
Adverse Device Effect 
Adverse Event 
Atrial Fibrillation 
Anticipated Serious Adverse Device Effect 
Atrioventricular 
Biventricular 
Coronary Artery Bypass Graft 
Cardiac Output 
Clinical Investigational Plan 
Case Report Form 
Cardiac Resynchronization Therapy- Defibrillator 
Data Management Plan 
Ethics Committee 
Echocardiography 
Electronic Case Report Form 
Electronic Data Capture 
Ejection Fraction 
Heart Failure 
Implantable Cardioverter Defibrillator 
Institutional Review Board 
International Organization for Standardization 
Left Ventricle 
Left Ventricle End Diastolic Diameter 
Left Ventricle End Diastolic Volume 
Left Ventricle Ejection Fraction  
Left Ventricle End Systolic Diameter  
Left Ventricle End Systolic Volume 
Left Ventricle Outflow Tract 
MultiPointTM Pacing 
New York Heart Association 
Patient Care System 
Principal Investigator 
Pacemaker 
Phrenic Nerve Stimulation 
Percutaneous Transluminal Coronary Angioplasty 
Right Auricle 
Right Ventricle 
Serious Adverse Device Effect 
Serious Adverse Event 

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SPP 
SC  
SJM 
USADE 
VTI 
WMA 
SinglePoint Pacing 
Steering Committee 
St. Jude Medical 
Unanticipated Serious Adverse Device Effect 
Velocity Time Integral 
World Medical Association 
 
 
 

Study Document No: SJM-CIP-10058 
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APPENDIX B: CIP REVISION HISTORY 
 
Revision History 
Amendment 
Number 
Version 
Date 
Rationale 
Details 
Not 
Applicable 
A 
21APR2015 
First release of CIP 
NA 
 
 
 

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APPENDIX C: DECLARATION OF HELSINKI 
Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964 and 
amended by the: 
29th WMA General Assembly, Tokyo, Japan, October 1975 35th 
WMA General Assembly, Venice, Italy, October 1983 
41st WMA General Assembly, Hong Kong, September 1989 
48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996 52nd WMA 
General Assembly, Edinburgh, Scotland, October 2000 
53rd WMA General Assembly, Washington DC, USA, October 2002 (Note of Clarification added) 
55th WMA General Assembly, Tokyo, Japan, October 2004 (Note of Clarification added) 59th WMA 
General Assembly, Seoul, Republic of Korea, October 2008 
64th WMA General Assembly, Fortaleza, Brazil, October 2013 
 
Preamble 
− The World Medical Association (WMA) has developed the Declaration of Helsinki as a 
statement  of ethical principles for medical research  involving human subjects, including 
research on identifiable human material and data. 
The Declaration is intended to be read as a whole and each of its constituent paragraphs should 
be applied with consideration of all other relevant paragraphs. 
− Consistent with the mandate of the WMA, the Declaration is addressed primarily to physicians.  
The WMA encourages  others who  are  involved  in  medical  research involving human 
subjects to adopt these principles. 
 
General Principles 
− The Declaration of Geneva of the WMA binds the physician with the words, “The health of my 
patient will be my first consideration,” and the International Code of Medical Ethics declares 
that, “A physician shall act in the patient's best interest when providing medical care.” 
− It is the duty of the physician to promote and safeguard the health, well-being and rights  of  
patients,  including  those  who  are  involved  in  medical  research.  The physician's 
knowledge and conscience are dedicated to the fulfilment of this duty. 
− Medical progress is based on research that ultimately must include studies involving human 
subjects. 
− The primary purpose of medical research involving human subjects is to understand the causes, 
development and effects of diseases and improve preventive, diagnostic and therapeutic 
interventions (methods, procedures and treatments). Even the best proven interventions must be 
evaluated continually through research for their safety, effectiveness, efficiency, accessibility 
and quality. 
− Medical research is subject to ethical standards that promote and ensure respect for all human 
subjects and protect their health and rights. 
− While the primary purpose of medical research is to generate new knowledge, this goal can 

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never take precedence over the rights and interests of individual research subjects. 
− It is the duty of physicians who are involved in medical research to protect the life, health, 
dignity, integrity, right to self-determination, privacy, and confidentiality of personal 
information of research subjects. The responsibility for the protection of research  subjects  
must  always  rest  with  the  physician  or  other  health  care professionals and never with the 
research subjects, even though they have given consent. 
− Physicians must consider the ethical, legal and regulatory norms and standards for research 
involving human subjects in their own countries as well as applicable international norms and 
standards. No national or international ethical, legal or regulatory requirement should reduce or 
eliminate any of the protections for research subjects set forth in this Declaration. 
− Medical research should be conducted in a manner that minimizes possible harm to the 
environment. 
− Medical research involving human subjects must be conducted only by individuals with  the  
appropriate  ethics  and  scientific  education,  training  and  qualifications. Research on patients 
or healthy volunteers requires the supervision of a competent and appropriately qualified 
physician or other health care professional. 
− Groups that are underrepresented in  medical research should  be  provided appropriate access 
to participation in research. 
− Physicians who combine medical research with medical care should involve their patients in 
research only to the extent that this is justified by its potential preventive, diagnostic or 
therapeutic value and if the physician has good reason to believe that participation in the 
research study will not adversely affect the health of the patients who serve as research subjects. 
− Appropriate compensation and treatment for subjects who are harmed as a result of 
participating in research must be ensured. 
 
Risks, Burdens and Benefits 
− In medical practice and in medical research, most interventions involve risks and burdens. 
Medical research involving human subjects may only be conducted if the importance of the 
objective outweighs the risks and burdens to the research subjects. 
− All medical research involving human subjects must be preceded by careful assessment of 
predictable risks and burdens to the individuals and groups involved in the research in 
comparison with foreseeable benefits to them and to other individuals or groups affected by the 
condition under investigation. 
Measures to minimise the risks must be implemented. The risks must be continuously 
monitored, assessed and documented by the researcher. 
− Physicians may not be involved in a research study involving human subjects unless they  are  
confident  that  the  risks  have  been  adequately  assessed  and  can  be satisfactorily managed. 
When the risks are found to outweigh the potential benefits or when there is conclusive proof of 
definitive outcomes, physicians must assess whether to continue, modify or immediately stop 
the study. 
 
Vulnerable Groups and Individuals 

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− Some groups and individuals are particularly vulnerable and may have an increased likelihood 
of being wronged or of incurring additional harm. 
All vulnerable groups and individuals should receive specifically  considered protection. 
− Medical research with a vulnerable group is only justified if the research is responsive to the 
health needs or priorities of this group and the research cannot be carried out in a non-
vulnerable group. In addition, this group should stand to benefit from the knowledge, practices 
or interventions that result from the research. 
 
Scientific Requirements and Research Protocols 
− Medical research involving human subjects must conform to generally accepted scientific 
principles, be based on a thorough knowledge of the scientific literature, other relevant sources 
of information, and adequate laboratory and, as appropriate, animal experimentation. The 
welfare of animals used for research must be respected. 
− The design and performance of each research study involving human subjects must be clearly 
described and justified in a research protocol. 
The protocol should contain a statement of the ethical considerations involved and should 
indicate how the principles in this Declaration have been addressed. The protocol   should   
include   information   regarding   funding,   sponsors,   institutional affiliations,  potential  
conflicts  of  interest,  incentives  for  subjects  and  information regarding provisions for 
treating and/or compensating subjects who are harmed as a consequence of participation in the 
research study. 
In clinical trials, the protocol must also describe appropriate arrangements for post- trial 
provisions. 
 
Research Ethics Committees 
− The research protocol must be submitted for consideration, comment, guidance and approval 
to the concerned research ethics committee before the study begins. This committee must be 
transparent in its functioning, must be independent of the researcher, the sponsor and any 
other undue influence and must be duly qualified. It must take into consideration the laws and 
regulations of the country or countries in which the research is to be performed as well as 
applicable international norms and standards but these must not be allowed to reduce or 
eliminate any of the protections for research subjects set forth in this Declaration. 
The committee must have the right to monitor ongoing studies. The researcher must provide 
monitoring information to the committee, especially information about any serious adverse 
events. No amendment to the protocol may be made without consideration and approval by 
the committee. After the end of the study, the researchers must submit a final report to the 
committee containing a summary of the study’s findings and conclusions. 
 
Privacy and Confidentiality 
− Every precaution must be taken to protect the privacy of research subjects and the 
confidentiality of their personal information. 
 
Informed Consent 

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− Participation by individuals capable of giving informed consent as subjects in medical research 
must be voluntary. Although it may be appropriate to consult family members or community 
leaders, no individual capable of giving informed consent may be enrolled in a research study 
unless he or she freely agrees. 
− In medical research involving human subjects capable of giving informed consent, each 
potential subject must be adequately informed of the aims, methods, sources of funding, any 
possible conflicts of interest, institutional affiliations of the researcher, the anticipated benefits 
and potential risks of the study and the discomfort it may entail, post-study provisions and any 
other relevant aspects of the study. The potential subject must be informed of the right to refuse 
to participate in the study or to withdraw consent to participate at any time without reprisal. 
Special attention should be given to the specific information needs of individual potential 
subjects as well as to the methods used to deliver the information. 
After ensuring that the potential subject has understood the information, the physician or 
another appropriately qualified individual must then seek the potential subject’s freely-given 
informed consent, preferably in writing. If the consent cannot be expressed in writing, the non-
written consent must be formally documented and witnessed. 
All medical research subjects should be given the option of being informed about the general 
outcome and results of the study. 
− When seeking informed consent for participation in a research study the physician must be 
particularly cautious if the potential subject is in a dependent relationship with the physician or 
may consent under duress. In such situations the informed consent must be sought by an 
appropriately qualified individual who is completely independent of this relationship. 
− For a potential research subject who is incapable of giving informed consent, the physician 
must seek informed consent from the legally authorised representative. These individuals must 
not be included in a research study that has no likelihood of benefit for them unless it is 
intended to promote the health of the group represented by the potential subject, the research 
cannot instead be performed with persons capable of providing informed consent, and the 
research entails only minimal risk and minimal burden. 
− When a potential research subject who is deemed incapable of giving informed consent  is  able  
to  give  assent  to  decisions  about  participation  in  research,  the physician must seek that 
assent in addition to the consent of the legally authorized representative. The potential subject’s 
dissent should be respected. 
− Research involving subjects who are physically or mentally incapable of giving consent, for 
example, unconscious patients, may be done only if the physical or mental condition that 
prevents giving informed consent is a necessary characteristic of the research group. In such 
circumstances the physician must seek informed consent  from  the  legally  authorised  
representative.  If  no  such  representative  is available and if the research cannot be delayed, 
the study may proceed without informed consent provided that the specific reasons for 
involving subjects with a condition that renders them unable to give informed consent have 
been stated in the research protocol and the study has been approved by a research ethics 
committee. Consent to remain in the research must be obtained as soon as possible from the 
subject or a legally authorised representative. 
− The physician must fully inform the patient which aspects of their care are related to the 

Study Document No: SJM-CIP-10058 
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without the express written consent of St. Jude Medical  
 
research. The refusal of a patient to participate in a study or the patient’s decision to withdraw 
from the study must never adversely affect the patient-physician relationship. 
− For medical research using identifiable human material or data, such as research on material or 
data contained in biobanks or similar repositories, physicians must seek informed consent for its 
collection, storage and/or reuse. There may be exceptional situations where consent would be 
impossible or impracticable to obtain for such research. In such situations the research may be 
done only after consideration and approval of a research ethics committee. 
 
Use of Placebo 
− The benefits, risks, burdens and effectiveness of a new intervention must be tested against those 
of the best proven intervention(s), except in the following circumstances: 
Where no proven intervention exists, the use of placebo, or no intervention, is acceptable; or  
Where for compelling and scientifically sound methodological reasons the use of any 
intervention  less  effective  than  the best  proven  one,  the use  of  placebo,  or  no 
intervention is necessary to determine the efficacy or safety of an intervention 
and the patients who receive any intervention less effective than the best proven one, placebo, 
or no intervention will not be subject to additional risks of serious or irreversible harm as a 
result of not receiving the best proven intervention. 
Extreme care must be taken to avoid abuse of this option. 
 
Post-Trial Provisions 
− In advance of a clinical trial, sponsors, researchers and host country governments should make 
provisions for post-trial access for all participants who still need an intervention identified as 
beneficial in the trial. This information must also be disclosed to participants during the 
informed consent process. 
 
Research Registration and Publication and Dissemination of Results 
− Every research study involving human subjects must be registered in a publicly accessible 
database before recruitment of the first subject. 
− Researchers, authors, sponsors, editors and publishers all have ethical obligations with  regard  
to  the  publication  and  dissemination  of  the  results  of  research. Researchers have a duty to 
make publicly available the results of their research on human subjects and are accountable for 
the completeness and accuracy of their reports.  All  parties  should  adhere  to  accepted  
guidelines  for  ethical  reporting. Negative and inconclusive as well as positive results must be 
published or otherwise made publicly available. Sources of funding, institutional affiliations 
and conflicts of interest must be declared in the publication. Reports of research not in 
accordance with the principles of this Declaration should not be accepted for publication. 
 
Unproven Interventions in Clinical Practice 
− In the treatment of an individual patient, where proven interventions do not exist or other 
known interventions have been ineffective, the physician, after seeking expert advice, with 
informed consent from the patient or a legally authorised representative, may use an unproven 

Study Document No: SJM-CIP-10058 
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without the express written consent of St. Jude Medical  
 
intervention if in the physician's judgement it offers hope of saving life, re-establishing 
health or alleviating suffering. This intervention should subsequently be made the object of 
research, designed to evaluate its safety and efficacy. In all cases, new information must 
be recorded and, where appropriate, made publicly available. 

Study Document No: SJM-CIP-10058 
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Study Name: QUARTO III study 
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without the express written consent of St. Jude Medical  
 
APPENDIX D: PROGRAMMING GUIDELINES 
The purpose of this appendix is to provide additional information regarding specific study 
activities and or procedures. 
Additional information will be provided when the new Auto Vect SelectTM tool is commercially 
available and regulatory approved. 
 
Part 1 – MPP Cathode selection   
 
There are two important requirements at the time of the implant for the success of the MultiPointTM 
Pacing feature activation during the study: 
 
- 
The LV lead must be completely placed within the target vein. All the 4 poles should be within the 
target vein, allowing them to work so maximizing the number of valid configurations. 
- 
A MPP Vector Test needs to be performed in order to establish if the MPP feature can be turned 
ON. Capture thresholds and PNS should be measured in all the 4 poles, in order to know the 
number of vectors available when using the MPP feature. In order to allow the MPP feature to be 
turned ON, a patient will need to have at least 2 vectors from different groups (with different 
Cathodes) that fulfills the following conditions: 
o Capture threshold does not exceed 4.5 V at 0.5ms pulse width 
o No Phrenic Nerve Stimulation (PNS) at 1 Volt above the programmed LV output 
 
Vectors are divided in 4 groups depending on the Cathode, as follows: 
- Group A: includes all the possible vectors using D1 as cathode 
- Group B: includes all the possible vectors using M2 as cathode 
- Group C: includes all the possible vectors using M3 as cathode 
- Group D: includes all the possible vectors using P4 as cathode 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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To follow this method it is available a RV-LV Conduction Delays Test that automatically identify the 
RV-LV conduction time for each LV pole. The test is performed automatically with the Merlin PCS 
programmer and the overall duration of the test is around 60-90 seconds. 
 
Performing the RV-LV Conduction Delays Test 
  
• 
Interrogate the device with Merlin PCS programmer and select the Option Print Menu in 
order to activate the CRT Toolkit (if not already active) 

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Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
                                                                                                       Page 70 of 87  
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed or used 
without the express written consent of St. Jude Medical  
 
  
 
 
• 
Pressing  on  “Perform  Measurements”  the  test  will  take  place  using  the  temporary 
parameters. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• 
In case that is not possible to pace (RV paced test) the measurement will fail. 
• 
Please ensure a programming that will allow the testing. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
 
 
Template 90153521 Ver B                                                                                                                       Page 73 of 87  
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed or used 
without the express written consent of St. Jude Medical  
 
 
 
 
 
 
 
 
 
 
• MultiPoint™ Pacing Settings in Basic Operation 
 
 
 
 
 
 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
 
 
Template 90153521 Ver B                                                                                                                       Page 74 of 87  
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed or used 
without the express written consent of St. Jude Medical  
 
 
 
• To turn the feature ON, go to Ventricular Pacing and select appropriate configuration 
(LV1LV2RV). 
− MultiPoint™ Pacing available for base rate ≤ 110 bpm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• When MultiPoint Pacing is turned ON, the desired vector configuration is programmed. Delay 1 and 
Delay 2 can also be adjusted from this screen 
 
 
 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
 
 
Template 90153521 Ver B                                                                                                                       Page 75 of 87  
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed or used 
without the express written consent of St. Jude Medical  
 
 
• When MPP is turned ON, the Basic Operation screen updates  
 
 
 
 
 
Part 3 – MPP Capture Thresholds Test   
 
To ensure a proper capture in both LV1 and LV2, next steps should be followed: 
 
1. Display a custom IEGM vector where the first electrode is the cathode of LV1 pacing vector and 
the second electrode is the cathode of LV2 pacing vector. (For example, if the LV1 configuration 
is D1-M2 and the LV2 configuration is P4-RVcoil, the custom sensing vector should be D1-P4.) 
2. Program an AV delay during testing to ensure ventricular capture from LV1 electrode. Turn off 
RVCap™ Confirm and LVCap™ Confirm during testing.   
3. Turn on MPP with the desired LV1 and LV2 pacing vectors. Program RV, LV1 and LV2 with 
sufficient safety margin to ensure capture with each pacing pulse. Program Delay 1 and Delay 2 
to the desired settings. 
4. The test should begin at a setting that achieves capture from RV, LV1 and LV2. It is 
recommended to collect a freeze capture illustrating capture from RV, LV1 and LV2 (baseline). 
Denote pulse amplitude settings for all vectors on the freeze capture. 
5. When capture takes place on both LV1 and LV2 at very short timing delay, the evoked responses 
on the IEGM using LV1 cathode-LV2 cathode will largely cancel each other. Capture on both 
electrodes should give a distinct morphology, compared to capture at either electrode alone. 
 
 
 
 
 
 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
 
 
Template 90153521 Ver B                                                                                                                       Page 76 of 87  
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed or used 
without the express written consent of St. Jude Medical  
 
 
- 
Capture from RV and LV1, and LV2 (baseline): 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6. Decrease output of LV2 temporarily under the “Sense & Capture” screen on the Merlin PCS 
until you see a change in morphology on a custom sensing vector EGM 
7. If there is no morphology change at low LV2 output, shorten the LV1-LV2 timing delay and 
repeat steps (5ms is the shortest timing delay).  
8. Collect a freeze capture illustrating MPP with capture on LV1 only. Mark the output value at 
which capture from LV1 only, but not LV2 was achieved. 
 
- 
Capture from RV and LV1, but not LV2 
 
           
 
 
9. The same process should be followed with both LV pacing vectors 
 
 
 
i.e.: 
LV1 vector – D1M2 
LV2 vector – P4RV Coil 
LV1-LV2 timing delay – 10 ms 
LV2 pacing output – 4 V 
Both LV1 and LV2 capture 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
 
 
Template 90153521 Ver B                                                                                                                       Page 77 of 87  
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed or used 
without the express written consent of St. Jude Medical  
 
 
APPENDIX E: DATA COLLECTION METHOD 
Sponsor/Investigators are required to prepare and maintain adequate an accurate case histories 
designed to record all observations and other data pertinent to the investigation on each subject 
1:1. Source documents include all original records from which CRFs derive their data.  Worksheet 
can be provided. The purpose of these worksheets is to aid investigators in the capture  of  
clinical  investigational data  and  ensure  all  protocol  required  data,  which  is  not captured in 
medical records, is recorded to support data for the investigation. These worksheets will not be a 
copy of the eCRFs, but will contain entry blanks for study required data not routinely collected by 
the investigators. 
 
All documentation pertaining to clinical assessments and medical evaluations should be signed and 
dated by the appropriate clinical personnel. 
 
Electronic Data Capture (EDC) will be used for this investigation, therefore, please find below 
instructions on how to access and use the eCRF application. 
 
Access to eCRF application 
The eCRF application is accessed through the internet and requires the use of a personal user 
account and password. 
The following documents and information are required prior to receipt of personnel user account 
and password: 
 
• 
Current signed and dated CV 
• 
Completed Signature and Delegation List 
• 
Documented training 
• 
Email address and telephone 
 
Personal user account and password are provided via email. User account and password are 
confidential and personal. They are not to be shared with other people. 
The first time the application is accessed, the password will need to be changed. 
If the password is forgotten and/or lost, a new password can be provided via email by following 
the instructions on the webpage. 
 
Each center must be authorized to start enrolling patients in the investigation before access 
privileges to the application is made available. 
 
Access privileges are based on the tasks assigned on the Signature and Delegation List and will be 
either: 
 
• 
Data entry and review 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
 
 
Template 90153521 Ver B                                                                                                                       Page 78 of 87  
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed or used 
without the express written consent of St. Jude Medical  
 
 
• 
Data entry, review and sign off 
 
All eCRFs must be completed, saved (‘save complete’) and approved by an investigator in a 
timely manner. 
 
In order to ensure a timely event reporting to the authorities (as per local regulations), particular 
attention must be used with Adverse Events forms. The Site is required to always “save as 
complete” the Adverse Event eCRFs. 
 
 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
 
 
Template 90153521 Ver B                                                                                                                       Page 79 of 87  
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed or used 
without the express written consent of St. Jude Medical  
 
 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
 
 
Template 90153521 Ver B                                                                                                                       Page 80 of 87  
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed or used 
without the express written consent of St. Jude Medical  
 
 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
 
 
Template 90153521 Ver B                                                                                                                       Page 81 of 87  
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed or used 
without the express written consent of St. Jude Medical  
 
 
Attachment to CRF  
 
The feature “Attachment to CRFs” is available to the centers to upload the requested documents.  
The “Attachment to CRFs” is designed to upload images, adobe acrobat files, and scanned documents. 
In case of Quarto III, Fluoroscopy Images will be uploaded to document the final lead and electrodes 
position. 
 
Please find below the instructions for use: 
 
• 
Login to EDC Study Portal  
 
https://studyedc.sjm.com  
 
 
 
1. 
Click on “Attachment to CRF” to launch Files Uploading Utility. 
 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
 
 
Template 90153521 Ver B                                                                                                                       Page 82 of 87  
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed or used 
without the express written consent of St. Jude Medical  
 
 
 
 
 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
 
 
Template 90153521 Ver B                                                                                                                       Page 83 of 87  
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed or used 
without the express written consent of St. Jude Medical  
 
 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
 
 
Template 90153521 Ver B                                                                                                                       Page 84 of 87  
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed or used 
without the express written consent of St. Jude Medical  
 
 
 
 
 
 
 
 
 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
 
 
Template 90153521 Ver B                                                                                                                       Page 85 of 87  
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed or used 
without the express written consent of St. Jude Medical  
 
 
 
APPENDIX F: LIST OF CLINICAL INVESTIGATION SITES AND IRB/EC 
A list of Clinical Investigational sites and IRB/EC will be kept under a separate cover and is available 
upon request.  
 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
 
 
Template 90153521 Ver B                                                                                                                       Page 86 of 87  
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed or used 
without the express written consent of St. Jude Medical  
 
 
APPENDIX G: SAMPLE INFORMED CONSENT 
 
 
 

Study Document No: SJM-CIP-10058 
Ver. A 
Study Name: QUARTO III study 
CIP  
 
 
 
Template 90153521 Ver B                                                                                                                       Page 87 of 87  
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed or used 
without the express written consent of St. Jude Medical  
 
 
APPENDIX H: CASE REPORT FORMS