ECG Belt for CRT Response
Phase: NA
Conditions: Heart Failure
Sponsor: Medtronic Cardiac Rhythm and Heart Failure

 
 
Clinical Investigation Plan Title 
ECG Belt for CRT Response 
Clinical Investigation Plan Identifier 
MDT 
Study Product 
ECG Belt  
ClinicalTrials.gov Identifier 
NCT03504020 
Sponsor 
Medtronic 
8200 Coral Sea St NE 
Mounds View, MN  55112 
Document Title 
ECG Belt for CRT Response Clinical Investigation Plan 
Document Version (Date) 
5.0 (02MAY2019) 
 

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Revision 1A 
 
 
 
 
ECG Belt for CRT 
Response 
 
 
Clinical Investigation Plan 
 
Version 5.0 
02MAY2019 
 
Regional Sponsors and Contacts  
United States 
Medtronic Inc. 
8200 Coral Sea Street NE 
Mounds View, MN U.S.A. 55112 
1-800-328-2518 
Europe 
Medtronic, Bakken Research Center B.V. 
Endepolsdomein 5 
6229 GW Maastricht 
The Netherlands 
+31-43-35-66-566 
Canada 
Medtronic of Canada 
99 Hereford Street 
Brampton, Ontario, L6Y 0R3 Canada 
+1-905-460-3800 
 
Confidentiality Statement 
The information contained in this document is confidential and the proprietary property of 
Medtronic. Any distribution, copying, or disclosure without the prior written authorization 
of Medtronic is strictly prohibited. Persons to whom the information is disclosed must 
know that it is confidential and that it may not be further disclosed by them. 
 
 

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TABLE OF CONTENTS 
Listing of Tables & Figures .............................................................................................. 5 
Sponsor Contact Information ........................................................................................... 6 
CRO and Core Labs ........................................................................................................ 7 
Steering Committee ......................................................................................................... 7 
1. 
Synopsis ........................................................................................................ 8 
2. 
Introduction .................................................................................................. 12 
a. 
Study purpose .............................................................................................. 12 
b. 
Study description ......................................................................................... 12 
3. 
Background and Justification ....................................................................... 12 
4. 
System Description and Intended Use ......................................................... 16 
a. 
Investigational system description ................................................................ 16 
b. 
Intended use investigational system ............................................................. 19 
c. 
Other devices and equipment used in the study ........................................... 19 
5. 
Regulatory Compliance ................................................................................ 20 
6. 
Methodology ................................................................................................ 21 
a. 
Primary Objective ......................................................................................... 21 
b. 
Ancillary Objectives ...................................................................................... 22 
c. 
Subject selection criteria and enrollment ...................................................... 22 
i. 
Inclusion criteria 
22 
ii. 
Exclusion criteria 
22 
d. 
Randomization ............................................................................................. 23 
e. 
Blinding ........................................................................................................ 23 
f. 
Minimization of Bias ..................................................................................... 23 
7. 
Study Procedures ........................................................................................ 24 
a. 
Investigator / Investigation site selection ...................................................... 24 
b. 
Site activation .............................................................................................. 24 
c. 
Equipment requirements .............................................................................. 25 
d. 
Data collection ............................................................................................. 26 
e. 
Role of the sponsor representatives ............................................................. 27 
f. 
Patient informed consent process ................................................................ 27 
g. 
Baseline (pre-CRT implant) data collection .................................................. 29 
h. 
Randomization ............................................................................................. 30 
i. 
Implant ......................................................................................................... 30 
i. 
ECG Belt arm: CRT device implant and recommended programming 
30 
ii. 
Control arms A and B: CRT device implant and programming 
31 
j. 
Scheduled Follow-up Visits .......................................................................... 33 
k. 
Post-Implant Follow-Up ................................................................................ 33 
i. 
ECG Belt arm: Post-Implant Follow-Up CRT programming 
34 
ii. 
Control arms A and B:  Post-Implant Follow-Up CRT programming 
36 

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l. 
6-Month Follow-up Visit ................................................................................ 37 
i. 
ECG Belt arm and control arm A:  6 month follow-up CRT programming 
38 
ii. 
Control arm B:  6 month follow-up CRT recommended programming 
39 
m. 
9-Month Follow-up Visit ................................................................................ 39 
n. 
Device Interrogation ..................................................................................... 40 
o. 
Healthcare Utilization ................................................................................... 40 
p. 
System Modification ..................................................................................... 41 
q. 
Study Exit..................................................................................................... 41 
r. 
Medications .................................................................................................. 42 
8. 
Investigational device/software storage, handling and traceability ................ 43 
9. 
Study Deviations .......................................................................................... 43 
10. 
Adverse events and Device Deficiencies ..................................................... 44 
a. 
Adverse Event and Device Deficiency definitions ......................................... 44 
b. 
Adverse Event and Device Deficiency Assessment ..................................... 47 
i. 
Adverse Events 
47 
ii. 
Device Deficiencies 
47 
iii. 
Processing Updates and Resolution 
47 
c. 
Adverse Events and Deficiency Classification .............................................. 48 
d. 
Adverse Event and Device Deficiency Reporting Requirements .................. 49 
e. 
Subject Death .............................................................................................. 53 
i. 
Death data collection 
53 
ii. 
Death classification and reporting 
53 
f. 
Clinical event review .................................................................................... 54 
g. 
Product Complaint Reporting ....................................................................... 54 
11. 
Risk Analysis ............................................................................................... 55 
a. 
Risk Minimization ......................................................................................... 57 
b. 
Potential Benefits ......................................................................................... 58 
c. 
Risk-benefit rationale ................................................................................... 58 
12. 
Planned study closure, early termination of study or study suspension ........ 59 
a. 
Planned study closure .................................................................................. 59 
b. 
Early termination or suspension ................................................................... 59 
i. 
Study-wide termination or suspension 
59 
ii. 
Investigator/center termination or suspension 
59 
c. 
Procedures for termination or suspension .................................................... 60 
i. 
Medtronic-initiated and regulatory authority-initiated 
60 
ii. 
Investigator-initiated 
60 
iii. 
Ethics committee-initiated 
60 
13. 
Statistical methods and data analysis .......................................................... 61 
a. 
Sample size determination ........................................................................... 61 
b. 
General considerations ................................................................................ 61 
c. 
Primary Objective ......................................................................................... 61 
i. 
Hypothesis 
62 
ii. 
Performance Requirements 
62 

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iii. 
Rationale for Performance Criteria 
62 
iv. 
Analysis Methods 
62 
v. 
Determination of Subjects for Analysis 
62 
vi. 
Sample Size 
62 
d. 
Ancillary Objectives ...................................................................................... 64 
e. 
Ancillary Objective #1................................................................................... 64 
i. 
Endpoint Definition 
64 
ii. 
Analysis Methods 
64 
iii. 
Determination of Subjects for Analysis 
64 
f. 
Ancillary Objective #2................................................................................... 64 
i. 
Endpoint Definition 
65 
ii. 
Analysis Methods 
65 
iii. 
Determination of Subjects for Analysis 
65 
g. 
Ancillary Objective #3................................................................................... 65 
i. 
Endpoint Definition 
65 
ii. 
Analysis Methods 
65 
iii. 
Determination of Subjects for Analysis 
65 
h. 
Ancillary Objective #4................................................................................... 65 
i. 
Endpoint Definition 
65 
ii. 
Analysis Methods 
66 
iii. 
Determination of Subjects for Analysis 
66 
i. 
Ancillary Objective #5................................................................................... 66 
i. 
Endpoint Definition 
66 
ii. 
Analysis Methods 
66 
iii. 
Determination of Subjects for Analysis 
67 
j. 
Ancillary Objective #6................................................................................... 67 
i. 
Endpoint Definition 
67 
ii. 
Analysis Methods 
67 
iii. 
Determination of Subjects for Analysis 
67 
k. 
Ancillary Objective #7................................................................................... 67 
i. 
Endpoint Definition 
67 
ii. 
Analysis Methods 
67 
iii. 
Determination of Data for Analysis 
67 
14. 
Data and quality management ..................................................................... 67 
15. 
Insurance information .................................................................................. 69 
16. 
Monitoring .................................................................................................... 69 
a. 
Monitoring Visits........................................................................................... 69 
17. 
Required records and reports....................................................................... 70 
a. 
Investigator records ..................................................................................... 70 
b. 
Investigator reports ...................................................................................... 71 
c. 
Sponsor records........................................................................................... 72 
d. 
Sponsor reports ........................................................................................... 73 
Appendix A. 
Draft data collection elements (Case Report Forms) .............................. 76 
Appendix B. 
Preliminary publication plan.................................................................... 76 
Appendix C. 
Patient Informed Consent template ........................................................ 78 

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Appendix D. 
Participating investigators and institutions .............................................. 78 
Appendix E. 
IRB/MEC and Competent Authority list ................................................... 78 
Appendix F. 
Labeling ................................................................................................. 78 
Appendix G. 
Modifications to the CIP ......................................................................... 80 
Appendix H. 
Clinical investigation plan signature page ............................................... 90 
Appendix I. 
Bibliography ........................................................................................... 91 
 
 
LISTING OF TABLES & FIGURES 
Table 1: ECG Belt Research System components information ...................................... 17 
Table 2:  Data collection and study procedure requirements at subject visits ................ 26 
Table 3:  Data collection and study procedure requirements at subject visits ................ 33 
Table 4: Adverse Event definitions ................................................................................ 44 
Table 5:  Adverse Event classification responsibilities ................................................... 48 
Table 6: Adverse Event reporting requirements ............................................................. 49 
Table 7:  Potential risks and risk minimization strategy .................................................. 57 
Table 8: LVESV Results from Previous CRT Studies’ CRT Patients .............................. 62 
Table 9: Investigator reports applicable for all geographies per Medtronic requirements
 ...................................................................................................................................... 71 
Table 10:  Additional Investigator reports applicable to the United States per FDA 
regulations .................................................................................................................... 71 
Table 11:  Additional Investigator reports applicable to Europe per ISO14155............... 72 
Table 12: Sponsor reports for Canada ........................................................................... 73 
Table 13: Sponsor reports for Europe............................................................................ 74 
Table 14: Sponsor reports for the United States ............................................................ 75 
Table 15: Change history CIPv1.0 to CIPv2.0................................................................ 80 
Table 16: Change history CIPv2.0 to CIPv3.0................................................................ 82 
Table 17: Change history CIPv3.0 to CIPv4.0................................................................ 84 
Table 18: Change history CIPv4.0 to CIPv5.0 ............................................................... 87 
 
Figure 1: ECG Belt Research System ........................................................................... 18 
Figure 2: ECG Belt management workflow diagram at Implant ...................................... 32 
Figure 3: ECG Belt management workflow and recommend programming at Post-
Implant Follow-Up ......................................................................................................... 36 
Figure 4: Blinded ECG Belt data collection workflow diagram at Post-implant and 6 
Months Follow-Ups........................................................................................................ 37 
Figure 5: ECG Belt management workflow and programming recommendations at 6 
Months Follow Up ......................................................................................................... 38 
Figure 6: ECG Belt data collection workflow diagram at 9 Months Follow-Up ................ 40 
Figure 7: Primary Objective #1 Power Curve ................................................................. 64 
 
 
 

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SPONSOR CONTACT INFORMATION 
Medtronic contact information is provided below. This information is subject to change 
during the course of the clinical study. Periodic updates to study contact information will 
be sent to the centers as needed. 
Study Sponsors and Contacts 
Worldwide clinical study leader 
Dana Wigert, Sr. Prin. Clinical Research Specialist 
 
dana.wigert@medtronic.com
Canada 
Aarthi Kamath, Sr. Clinical Research Specialist 
 
 
aarthi.kamath@medtronic.com 
United States 
Peter Kratz, Sr. Clinical Research
 
 
peter.kratz@medtronic.com 
Europe 
Griet Wouters, Sr. Clinical Research Specialist 
 
griet.wouters@medtronic.com 
Scientist 
Subham Ghosh, Prin. Scientist 
 
subham.ghosh@medtronic.com 
Monitoring Contacts 
Europe 
Anja Hesse, Prin. Clinical Research Monitor 
  
anja.hesse@medtronic.com 
US and Canada 
Brandey Toliver, Sr. Clinical Research Monitor 
 
brandey.toliver@medtronic.com 

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CRO AND CORE LABS 
 
 
Contact Information  
Duties Performed 
Cognizant Technology Solutions 
 
500 Frank W. Burr Blvd. 
Teaneck, NJ 07666 
Direct Phone: (201) 801-0233 
Direct Fax: (201) 801-0243 
• 
Develop study electronic case report forms, edit checks, and 
study management reports. 
• 
Review of electronic case report forms, management of 
discrepancies, and coding of medications and deviations. 
Echo Core Lab 
 
The Ohio State University 
1960 Kenny Road 
Columbus, Ohio 43210 
• 
Provide visual pre-screen of baseline echo for each subject. A 
24-hour turnaround is required. 
• 
Confirm that all subjects included in the analysis have a 
readable echo. 
• 
Analyze in a blinded fashion all echocardiograms. 
• 
Enter data in Oracle Clinical Echo database. 
 
 
STEERING COMMITTEE 
 
Primary function of the Steering Committee is to provide input for development of the 
protocol and study design, and to develop the publication strategy. 
Committee Member  
Contact Information 
John Rickard, MD-Chair 
Cleveland Clinic 
9500 Euclid Ave J2-2 
Cleveland, OH 44195 
 
Email: rickarj2@ccf.org 
Mauro Biffi, MD 
Policlinico Sant' Orsola - Malpighi 
Via Massaranti 9 
40138 Bologna, Italy 
it 
Michael Gold, MD 
The Medical University of South 
Carolina 
25 Courtenay Dr 
Charleston, SC 29425 
 
Email: goldmr@musc.edu 
Kevin Jackson, MD 
Duke University Medical Center 
2301 Erwin Rd Rm 7451 Duke N 
Durham, NC 27705 
 
Email: k.j@duke.edu 
Kevin Vernooy, MD 
Maastricht University Medical Center 
Heart and Vascular Centre, Cardiology 
P. Debyelaan 25 
6229 HX Maastricht, The Netherlands 
 
 
Any additions/changes will be distributed under separate cover, upon request.  

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1. SYNOPSIS 
 
Title 
ECG Belt for CRT Response (ECG Belt) 
 
Purpose 
The purpose is to compare ECG Belt Research System managed cardiac 
resynchronization therapy (CRT) patients and a control CRT group with respect to left 
ventricular (LV) remodeling. The ECG Belt Research System will be used at implant 
and follow-up to help implanters choose a suitable LV pacing site within the 
recommended locations for LV lead implantation and optimize pacing vector/timing 
parameters in line with the EHRA/HRS 2012 expert consensus statement. 
The first 6 months of follow-up will focus on using the ECG Belt Research System to 
help choose pacing site, vector and post-implant follow-up pacing programming. From 6 
to 9 months the ECG Belt Research System will be used to further investigate more 
personalized programming at follow-up visits. 
 
Design 
Prospective, interventional, randomized, multi-center, investigational, pre-market 
research study. 
 
Investigational Medical Device 
The medical device under investigation is the investigational ECG Belt Research 
System that includes hardware and software components. 
 
Implanted System 
Use of a market-released Medtronic CRT device with AdaptivCRT and a market-
released Medtronic quadripolar LV lead is required. Any market-released right 
ventricular (RV) and right atrial (RA) leads can be used. 
 
Primary Objective 
Demonstrate benefit of using the ECG Belt Research System on reducing left 
ventricular end-systolic volume (LVESV) from baseline to 6 months post-implant 
compared to standard CRT. 
ECG Belt arm subjects will be compared with the control arm subjects (combined 
control arms A and B). 
A core lab blinded to randomization and follow up status will analyze the echo data and 
measure LVESV. 
 
Subject Population 
The study population is known to have a lower likelihood of response to CRT with 
typical LV lead placement and device programming without an option for evaluating if 
pacing resynchronizes the patient’s heart. The ECG Belt Research System may serve 
this unmet medical need. 
The study will enroll approximately 500 patients at approximately 48 centers in the US, 
Europe, and Canada in order to randomize 400 subjects. Each subject in the study 

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will be enrolled prior to CRT implant and will have 3 follow-ups: post-implant, 6-month, 
and 9-month. 
  
Intervention 
Upon screening of the baseline echo, eligible subjects will be randomized 2:1:1 to either 
the ECG Belt arm, control arm A, or control arm B respectively. The latter two arms are 
identically treated up until the 6-month follow-up and will be called the control arm as a 
whole.   
→ The ECG Belt arm will undergo ECG Belt Research System management at 
CRT implant to help choose pacing site and programmed vector. At Post-
Implant follow-up and at the 6-month follow-up visit the ECG Belt Research 
System will be used to guide vector and programming parameters. At the 9-
month visit the ECG Belt Research System will be used to collect data for 
research purposes only. 
→ Control arm A will undergo routine implant and blinded ECG Belt Research 
System data collection at the Post-Implant follow-up. ECG Belt Research 
System management at the 6-month visit will help choose vector and 
programming parameters. At the 9-month visit the ECG Belt Research System 
will be used to collect data for research purposes only. 
→ Control arm B will undergo routine CRT implant and blinded ECG Belt 
Research System data collection at both the Post-Implant and 6-month follow-
ups. At the 9-month visit The ECG Belt Research System will be used to 
collect data for research purposes only. 
 
Inclusion criteria 
• 
Indicated for CRT, with QRS duration ≥130 ms, and planned to be implanted 
with a market-released Medtronic CRT device with AdaptivCRT and a 
market-released Medtronic quadripolar LV lead. 
• 
Meets at least one of the following criteria: 
o QRS duration < 150 ms 
o Prior documented Myocardial Infarction 
o Non-LBBBa1  
• 
LVEDD ≥ 55 mm, as determined by site 
 
Exclusion criteria  
• 
Permanent/persistent atrial fibrillation (AF) or presenting with AF  
• 
Pre-existing or previous LV lead or other confounding devices e.g. Left 
Ventricular Assist Device, Vagal Nerve Stimulator 
• 
Currently implanted with implantable pulse generator (IPG) or implantable 
cardioverter defibrillator (ICD) with >10% RV pacing  
• 
Permanent complete atrioventricular (AV) block 
• 
Enrolled in a concurrent study that may confound the results of this study. Pre-
approval from the study manager is required for enrollment of a patient that is 
in a concurrent study.   
• 
Less than 1 year life expectancy 
                                                 
a   Does not meet Strauss definition of LBBB1: QS or rS in leads V1 and V2 and Mid-QRS 
notching or slurring in ≥2 of leads V1, V2, V5, V6, I, and aVL 

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• 
Vulnerable adults 
• 
Younger than 18 years of age  
 
Study Duration 
Study duration is approximately 3.5 years representing approximately 32 months 
of enrollment and 9 months of subject follow-up. 
 
Clinical Procedures and Data Collection 
• 
All subjects will undergo the ECG Belt Research System procedure per their 
randomization assignment (see schedule below). After the 9-month visit subjects 
will be exited. 
• 
For patients in the ECG Belt arm the implant site, vector and pacing 
programming will be guided by the ECG Belt Research System data. Through 
the 6-month visit AdaptivCRT is required off for subjects in the control arms. 
After 6 months AdaptivCRT is required to stay off for subjects in control arm B. 
After 6 months subjects in control arm A will have vector and pacing 
programming guided by the ECG Belt Research System data. 
• 
The following data will be collected for all subjects in all arms: 
o Echocardiogram (Echo) at baseline (pre-implant), and at 6- and 9-month 
follow-up visits  
o 12-lead ECG at baseline 
o Medical history and demographics at baseline 
o ACE/ARB, beta blockers, diuretics, and anti-arrhythmics use at baseline 
o Implanted CRT system information and characteristics 
o Device interrogations after implant and at the beginning and end of each 
follow-up visit 
o NYHA Functional Classification at baseline, 6 and 9 months 
o Minnesota Living with Heart Failure questionnaire at baseline, 6 and 9 
months 
o Six-Minute Walk Test at baseline and 6 months 
o Patient Global Assessment Score at 6 and 9 months 
o Adverse events (including hospitalizations and death) and system 
modifications as they occur 
 

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Study Diagram and Schedule 
 

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2. INTRODUCTION 
a. Study purpose 
Medtronic is sponsoring the ECG Belt for CRT Response (ECG Belt) study, a 
prospective, interventional, randomized, multi-center, investigational, pre-market 
research study.  
The primary purpose of this study is to evaluate the ECG Belt Research System as an 
additional diagnostic tool for optimizing CRT therapy. The ECG Belt Research System 
will be used to inform placement of the LV lead while satisfying the EHRA/HRS 
published guidelines for LV lead implantation, and for optimizing pacing programming 
parameters in CRT patients. The ECG Belt Research System will provide real-time on-
site feedback on CRT efficacy at the time of implant and follow-up.  
The first 6 months of follow-up will focus on using the ECG Belt Research System to 
help choose pacing site, vector and pacing programming. From 6 to 9 months the ECG 
Belt Research System will be used to further investigate more personalized 
programming and post-implant optimization at follow-ups. 
The study will focus on CRT patients that are known to have a lower likelihood of 
response to CRT with typical LV lead placement and device programming. These are 
CRT-indicated patients with a QRS duration ≥130 ms and LVEDD ≥55 mm who meet at 
least one of the following criteria: 
o QRS duration <150 ms 
o Prior documented Myocardial Infarction 
o Non-LBBB 
 
b. Study description 
The study is expected to be conducted at approximately 48 centers located in the United 
States, Europe, and Canada. Centers will be initiated in phases to ensure optimal 
implementation of the ECG Belt Research System. 
Approximately 500 subjects will be enrolled in the study to ensure 400 randomized 
subjects. Centers are expected to randomize 8 subjects on average during the course of 
the study. Centers that enroll faster than others will be allowed to do so in order to 
maintain an adequate enrollment rate, with a maximum of 40 randomized subjects at 
one center to limit bias. 
Study subjects will be followed for 9 months, unless there is a decision by Medtronic or 
regulatory authority to end the study early. The expected study duration is approximately 
3.5 years representing approximately 32 months of enrollment and 9 months of subject 
follow-up. 
 
3. BACKGROUND AND JUSTIFICATION 
Implantation of cardiac resynchronization therapy device typically requires three leads, 
one in right atrium (RA), one in right ventricle (RV) and one in left ventricle (LV). The RV 
lead is usually implanted first, RA lead is always implanted in patients with sinus rhythm 
or when there’s a chance of resumption of sinus rhythm in patients with atrial fibrillation. 

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Practice varies regarding placement of right sided lead but pacing threshold and sensing 
are usually the main factors for deciding lead location as there is no clear evidence on 
effect of right sided lead location on outcomes19. Avoiding phrenic nerve stimulation and 
having reasonable LV pacing thresholds also play a role in determining where to place 
the LV lead in the coronary sinus (CS) though several studies have shown that selection 
of specific LV sites for pacing may improve CRT outcomes.  Though initial studies 
suggested placement of LV lead in the lateral wall, more recent data19 have shown a 
broader spectrum of LV pacing site locations may provide good clinical response to 
CRT. Venography is recommended to evaluate candidate CS tributaries and 
consideration of fluoroscopic methods are helpful for determining anatomically optimal 
locations.  Smaller studies have shown potential benefit in targeting areas of late 
electrical activation for placement of LV lead.  These were based on timing from ECG 
QRS-onset to local LV activation (q-LV), intrinsic electrical delay between the RV lead 
and LV lead or even targeting areas of late mechanical activation identified using 
echocardiographic methods19. However, mostly standard-of-care approaches focus on 
placing the leads ‘anatomically’ rather than using more patient-specific physiological 
approaches that the ECG Belt System may provide. Multipolar leads with more 
stimulation points provide more pacing options which may also help get a more optimal 
pacing electrode and/or vector for pacing the LV.  
 
Post-implant follow-up mainly involves routine device interrogation and testing which 
includes checks on battery status, lead impedances, sensing amplitudes, pacing 
threshold tests in all three chambers, a percentage of biventricular or left ventricular 
pacing. Standard-of-care practices for optimization of device timing parameters like 
choice of pacing vectors, AV delay, VV delay etc. are more variable with some centers 
using device nominals or automatic optimization routines available with certain 
manufacturers. Echocardiography and/or 12-lead ECG may be also used to set these 
parameters though there is not a clear consensus on a programming strategy to 
maximize the benefit of this therapy. 
 
There are several unmet needs for patients with Heart Failure such as to reduce device 
complications, improve efficiency of care, and maximize CRT response.  
 
Medtronic CRT features, such as the AdaptivCRT algorithm2 have succeeded in 
improving incremental response. Even so, approximately 20-25% of patients still don’t 
appear to improve following CRT implant. LV lead position is an important factor 
governing CRT response. Based on physician surveys, a key unmet need for CRT 
implant procedures is a system/means to determine acute response to CRT pacing 
during the implant procedure. Such feedback may provide physicians the confidence 
that they are placing the LV lead in a location that will decrease cardiac electrical 
dyssynchrony while ensuring that all other clinical parameters are met including lead 
stability, avoidance of phrenic nerve stimulation and reasonable pacing capture 
thresholds. Such feedback may also be used during implant and/or follow-up to 
determine the most optimal pacing parameters in case of a multipolar LV lead. 
 
The ECG Belt Research System may provide a solution to this unmet need. The ECG 
Belt Research System 
 
y. These maps and metrics are computed during 
intrinsic rhythm as well as during pacing to determine the changes from intrinsic to 
pacing rhythm.  

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Initial feasibility studies have shown that improvement in ECG Belt system metrics of 
electrical heterogeneity from intrinsic to CRT pacing is a better predictor of LV reverse 
remodeling than standard ECG-based metrics (baseline QRS, morphology, or changes 
in paced QRS duration) or echocardiographic measures of radial strain3. There is also 
promise of achieving a better acute hemodynamic response by helping choose an 
optimal LV lead position, especially in a sub-group of CRT patients. This sub-group, 
historically known to be more challenging to respond, includes all non-LBBB or ischemic 
or LBBB patients with QRS duration less than 150 ms. Reduction in the ECG Belt 
system metrics of electrical heterogeneity from intrinsic rhythm to CRT paced rhythm 
had much higher accuracy towards identifying LV pacing sites which provided acute 
hemodynamic improvements than did other parameters like intrinsic interventricular 
delays (RV-LV timing)4 measured at different LV pacing sites or reduction in QRS width 
from intrinsic to CRT pacing. Continuous variable analyses have shown the ECG Belt 
system metrics of electrical heterogeneity, especially their changes from intrinsic to CRT 
pacing, exhibited a strong correlation with invasively measured LV pressure gradients 
obtained acutely by a Millar pressure catheter in the LV5. Measurement of acute 
response has been used previously in a study6 to identify responsive pacing sites in the 
LV for improved patient outcomes. But those studies involved invasive instrumentation 
for measuring LV pressure.  
 
An observational retrospective analysis7 involving ECG belt data at follow-up in 94 
patients, showed that measuring relative change in electrical heterogeneity from the belt 
at baseline and at optimized programming settings may help to personalize CRT to 
minimize heterogeneity and potentially maximize response. Optimization potential is 
similar regardless of pre-CRT QRS morphology or duration.  Body surface mapping can 
therefore possibly improve CRT response by individualizing device programming to 
minimize electrical dyssynchrony. In another published study8, device optimization in 
CRT patients with delayed enhancement (scar) on MRI improved EF and reduced 
electrical dyssynchrony from ECG Belt. 
 
Since the ECG Belt Research System is a noninvasive tool and its measurements have 
been shown in previous studies to correlate with invasively measured hemodynamic 
response, it can be an easy to use noninvasive tool for identifying a potentially adequate 
LV pacing site without risk of additional invasive equipment (e.g. pressure catheters) 
during implant. The strategic intent of this study is to gather evidence in support of the 
ECG Belt Research System as a key tool to maximize CRT response. 
 
A number of studies published in peer-reviewed journals and presented in peer-reviewed 
scientific sessions have indicated that CRT response is associated with favorable 
changes in the electrical activation of the heart which may be evaluated from ECG 
based measures or by direct or non-invasive mapping of electrical activation of the 
ventricles.  
 
Sweeney et al9 have shown that analysis of ventricular activation from the routine 12-
lead ECG and its changes from intrinsic to CRT pacing can predict reverse LV 
remodeling in LBBB patients (n=202) with NYHA Class III-IV heart failure and with 
ejection fraction <35%.  
 
Spatial patterns of ventricular activation during intrinsic rhythm and pacing in CRT 
patients have been studied with a noninvasive activation mapping technique called 

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electrocardiographic imaging (or mapping). Electrocardiographic imaging10,11, based on 
the inverse problem of electrocardiography, reconstructs epicardial electrical activation 
based on multi-electrode ECGs (body surface potential mapping) and a thoracic CT 
scan.  
 
A study of electrocardiographic imaging in ischemic heart failure patients (n=8) with 
varying degrees of coronary heart disease12 has shown variable activation patterns 
characterized by areas of slow conduction and conduction block whose effect on the 
overall activation of the left ventricle may be a key determinant of CRT response. It also 
demonstrated the sensitivity of electrical activation maps to device timings, especially 
during LV only fusion pacing.  
 
Another recent study by Ghosh et al13 using noninvasive electrocardiographic imaging 
has shown that CRT response in non-ischemic cardiomyopathy (n=25) is associated 
with a reduction of LV electrical dyssynchrony from intrinsic to CRT pacing. The study 
showed presence of lines of functional block in the left ventricle which change position 
depending on nature of the activation (intrinsic or single V-paced or biventricular-paced) 
and may affect electrical resynchronization.  
 
Similar metrics of electrical dyssynchrony derived from electrocardiographic imaging, 
indicative of the spatial heterogeneity in ventricular activation (which may be caused by 
block or regional slowing of conduction) have been investigated in a study involving 
narrow or normal QRS heart failure patients (n=9)14. Heterogeneities in activation maps 
and electrical dyssynchrony were observed in this group despite normal QRS duration. 
The potential of these patients to benefit from CRT was also suggested.  
 
In another abstract15, several measures of electrical dyssynchrony derived from 
Electrocardiographic Mapping (ECM) maps in patients (n=50) with wide and normal QRS 
durations were investigated for their utility in predicting short-term CRT response as 
identified by acute improvements in LV pressure. ECM metrics were able to successfully 
identify candidature for CRT, irrespective of QRS duration.  
 
In canine studies of resynchronization pacing in LBBB with and without scar, 
Rademakers et al16 have shown that best electrical resynchronization of the ventricles is 
associated with the best acute hemodynamic response as measured by changes in LV 
pressure and stroke volume.  
 
There is mounting clinical evidence of the importance of electrical activation in CRT 
response. The ECG Belt (the ECG Electrode Array component of the ECG Belt 
Research System)
 
ata from internal Medtronic studies17 show that the ECG Belt system can 
measure ventricular activation and its changes favorable for acute and chronic CRT 
response, with higher accuracy than QLV or QRS narrowing3,5. The present study 
evaluates if the ECG Belt Research System metrics can help choose an adequate LV 
lead pacing site at implant and optimize therapy at follow-up that improves LVESV 
response, an accepted surrogate for CRT response. 
 
The study will require enrollment of patients planned to be implanted with a device that 
has the AdaptivCRT feature and a Medtronic quadripolar LV lead. For the primary 
objective, the benefit of using the ECG Belt Research System to guide personalized 

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therapy with Medtronic market released CRT solutions, including AdaptivCRT will be 
investigated. Results of the AdaptivCRT trial show that AdaptivCRT BiV-LV pacing is 
non-inferior to echo-optimized CRT therapy18.  Use of a quadripolar LV lead provides the 
most options in choosing an optimal pacing vector. The research phase of the study will 
use the ECG Belt Research System to further investigate personalized CRT therapy at 
follow-ups. 
In summary, this clinical research study will focus on maximizing CRT response by 
applying a non-invasive, diagnostic tool (ECG Belt Research System) at implant that 
could help implanters choose a suitable LV pacing site within the coronary sinus venous 
tributaries which are the recommended targets for the LV lead implant according to 
EHRA/HRS expert consensus19, and optimize pacing parameters (e.g. timing, pacing 
vectors) at implant and follow-up.  
4. SYSTEM DESCRIPTION AND INTENDED USE
a. Investigational system description
The ECG Belt Research System is intended for research use only. It is a diagnostic tool 
to provide feedback on the efficacy of CRT pacing at the time of device implant or at 
device follow-up. The system allows measurement of electrical dyssynchrony during 
intrinsic rhythm and during CRT pacing and calculates the change in dyssynchrony 
between these measurements.  
Based on the degree of change in dyssynchrony and based on prior clinical research 
related to the correlation of these dyssynchrony measurements to acute measures of LV 
dP/dt, the investigational ECG Belt Software Application will give specific feedback to the 
user. Two metrics of electrical heterogeneity, e.g. SDAT and LVAT, will be computed by 
the software. SDAT is the Standard Deviation of Activation Times of all electrodes and 
provides a measure of global electrical heterogeneity. LVAT is the Left Ventricular 
Activation Time, computed by averaging the activation time of electrodes on the left body 
surface. Changes in LVAT and SDAT between the intrinsic rhythm and a paced setting 
(ΔLVAT(%) and ΔSDAT(%), respectively) can be considered the diagnostic mechanism 
of action of the system. Based on these two metrics, the ECG Belt Software Application 
will sort the resynchronization effect achieved among all tested pacing configurations 
from highest to lowest.  
When used for CRT management, the user will have the option to evaluate different 
pacing sites and CRT parameters. The primary goals of the feedback measurements are 
to provide the implanter with additional confidence that the patient will be a responder to 
CRT therapy and to provide effective CRT optimization at device follow-up. When used 
in blinded mode for data collection only, the software will record SDAT and LVAT values, 
but these will not be shown to the user. 
The study will be conducted using the ECG Belt Research System components 
described in Table 1 and illustrated in Figure 1. Further details (manufacturer, model 
number etc.) will be maintained in the Investigator’s Brochure. Future changes may 
occur with respect to the ECG Electrode Array, Software Application, Amplifier, and 
Tablet manufacturer and/or model during the study. A new version of the system may be 
incorporated that is market-approved in some geographies. Medtronic will ensure that 

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any future changes to the ECG Belt Research System do not impact the scientific 
soundness and safety of the study and IRBs/MECs are informed and have approved 
these changes per local requirement before use in the study. 
Instructions for use will be provided in the ECG Belt Research System’s User Manual. 
The following are body contacting materials found on the ECG Electrode Array (ECG 
Belt):  Polyethylene terephthalate (PET), LOCTITE UV Curable Dielectric Ink and 
Katecho Adhesive Hydrogel. 
 
Table 1: ECG Belt Research System components information  
System Component 
Investigational or 
Market-Released 
(applies in all 
regions) 
Functional Responsibilities 
ECG Electrode Array (ECG 
Belt) 
Investigational 
• 
Provides multiple electrodes that 
are in contact with the skin of the 
patient’s torso via the electrode  
Multi-Channel ECG Amplifier  
(includes the hardware, 
firmware, connector/adapter) 
Investigational 
• 
 
 
 
• 
Provides amplification, signal 
processing, A/D conversion and 
sampling of electrical potentials 
• 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 

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System Component 
Investigational or 
Market-Released 
(applies in all 
regions) 
Functional Responsibilities 
• 
Protected by drive level encryption 
and requires a password 
Tablet  
Market-Released 
• 
Runs the software application 
• 
Displays the user interface and 
accepts user inputs 
• 
Stores data 
• 
Provides power via USB to the 
multi-channel ECG amplifier 
• 
Provides an output to display to an 
external monitor 
• 
Provides at least three hours of 
operation when fully charged (must 
not be connected to wall power 
when connected to the subject) 
 
Traceability of all system components shall be achieved during and after the study 
through the lot numbers, batch numbers or serial number of the component assigned by 
the manufacturer. If the manufacturer has not assigned such an identifier, Medtronic will 
assign one. The tablet with pre-installed ECG Belt Software Application will be tracked 
as one item. 
 
The ECG Electrode Array will be referred to as the ECG Belt. ECG Belts are single use, 
so each subject in the ECG Belt arm will require 4 ECG Belts and subjects in control arm 
A and B will require 3 ECG Belts. This will result in the use of approximately 1400 ECG 
Belts throughout the course of the study. Approximately 55 Multi-Channel ECG 
Amplifiers/Adaptors and tablets pre-loaded with the ECG Belt Software Application will 
be available in the study. This will allow for one ECG Belt Research System per site and 
several backups per region.  
 
Figure 1: ECG Belt Research System 
 
 

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b. Intended use investigational system 
The ECG Belt Research System will be used at implant and device follow-up for CRT 
indicated patients. The ECG Belt is intended for single use. All other components are 
reusable. 
 
c. Other devices and equipment used in the study 
For this study patients are selected for which implant of a market-released Medtronic 
CRT device with AdaptivCRT and a Medtronic quadripolar LV lead is planned. Any 
market-released RV and RA leads are allowed. Systems will be used within their 
approved intended use, e.g. off-label use/programming is not allowed. 
A commercially available Medtronic CRT device with AdaptivCRT is required which may 
include (based on geographic availability): 
• 
Viva™ Quad XT CRT-D 
• 
Claria MRI™ Quad CRT-D SureScan™ 
• 
Amplia MRI™ Quad CRT-D SureScan™ 
• 
Percepta™ Quad CRT-P MRI SureScan™ 
• 
Serena™ Quad CRT-P MRI SureScan™ 
• 
Any future generation commercially available CRT Quad device with the 
AdaptivCRT™ algorithm  
A commercially available Medtronic quadripolar LV pacing lead is required unless 
placement is unsuccessful, in which case a commercially available, transvenous, 
Medtronic bipolar LV pacing lead may be used. 
Any compatible commercially available RV lead can be used. 
Any compatible commercially available RA lead can be used.  
Any market-released Medtronic programmer and analyzer can be used, for example 
CareLink Model 2090 Programmer with the Model 2290 Analyzer. Adaptors and cables 
will be used to test the leads during implant. 
An optional isolation transformer will be provided with the system in geographies where 
this is required. 
The Medtronic CareLink Model 2090 Programmer and software (or any market-released 
Medtronic programmer) are used to program the CRT device at implant and follow-ups. 
The programming head will be needed for communications with this device. 
Programmers from other manufacturers are not compatible with Medtronic devices. 
 

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5. REGULATORY COMPLIANCE 
This study will be conducted in compliance with international ethical and scientific quality 
standards, known as good clinical practice (GCP). GCP includes review and approval by 
an independent Ethics Board/IRB/MEC before initiating a study, continuing review of an 
ongoing study by an Ethics Boards, and obtaining and documenting the freely given 
informed consent of a subject before initiating the study. 
The ECG Belt study was designed to reflect the GCP principles outlined in ISO 
14155:2011 and other international clinical requirements outlined below. These include 
the protection of the rights, safety and well-being of human subjects, controls to ensure 
the scientific conduct and credibility of the clinical investigation and the definition of 
responsibilities of the sponsor and investigators. In accordance with ISO standard, the 
sponsor shall avoid improper influence on, or inducement of, the subject, monitor, any 
investigator(s) or other parties participating in, contributing to, the clinical investigation. 
All investigators shall avoid improper influence on or inducement of the subject, sponsor, 
monitor, other investigator(s) or other parties participating in or contributing to the clinical 
investigation. 
The ISO standard also informed study design in the areas of device deficiency reporting 
and risk evaluation, with the exception (to Section 6.4 of the ISO standard) that only 
those Adverse Events (AEs) considered related to the ECG Belt Research System and 
all Serious AEs will be collected. This ensures any AEs which could potentially be 
relevant will be collected.  
The study will be conducted in compliance with the Clinical Investigation Plan (CIP), 
federal, national and local laws, including data protection laws, regulations, standards, 
and requirements of the countries/geographies where the study is being conducted. The 
principles of the Declaration of Helsinki have been implemented through the patient 
informed consent process, Ethics Board/IRB/MEC approval, study training, clinical trial 
registration, preclinical testing, risk-benefit assessment and publication policy. 
In all geographies, the study will be conducted in compliance with 21 CFR Part 54. 
In the United States, the study will be conducted in compliance with 21 CFR Parts 11, 
50, 56, 812. This study does not require an IDE submission to FDA. However, all 
requirements in 812.2(b)(1) must be followed. The study will be conducted as a Non-
Significant Risk (NSR) study because it does not meet the definition of a significant risk 
device study.  
(1) The ECG Belt Research System does not contain any components intended 
as an implant. It is non-invasive and will be temporarily wrapped around the 
subject’s upper torso to collect electrical data. 
(2) The ECG Belt Research System is not for use in supporting or sustaining 
human life.  
(3) The ECG Belt Research System is not of substantial importance in 
diagnosing, curing, mitigating, treating disease, or otherwise preventing 
impairment of human health. Only subjects already planned for CRT implant 
will be enrolled in the study.  
(4) For subjects in the ECG Belt arm, LV lead placement will not be solely based 
on ECG Belt Research System data. The lead will be placed in a location 
based on ECG Belt Research System data if the location also satisfies other 
clinical criteria for lead placement (e.g., appropriate pacing thresholds, lack of 

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phrenic nerve stimulation, anatomic stability, etc.) according to the expert 
consensus statement on CRT implant and follow-up19. Similarly, the ECG Belt 
Research System will provide an additional tool for optimizing CRT therapy 
during follow up for subjects in the ECG Belt arm and control arm A. 
 
(5) The ECG Belt Research System does not otherwise present a potential for 
serious risk to the health, safety, or welfare of a subject.  
In Canada, the study will be conducted in accordance with Canada Medical Device 
Regulations,1998 (SOR/98-282), and the Guidance document for Mandatory Problem 
Reporting for Medical Devices, 2011(H164-145/201E). 
 
In Europe, the study will be conducted in compliance with ISO14155:2011 and in 
accordance with the Declaration of Helsinki version 2013 and local laws and 
requirements for pre-market research feasibility studies.  
Any additional requirements imposed by the regulatory authorities and independent 
medical ethics committee or institutional review board shall be followed. 
The study will be publicly registered prior to first enrollment in accordance with the 2007 
Food and Drug Administration Amendments Act (FDAAA) and Declaration of Helsinki on 
http://clinicaltrials.gov (PL 110-85, Section 810(a)).Approval of the CIP is required from 
the following groups prior to any study procedures at a study center:  
• 
Medtronic  
• 
Principal Investigators (where required by local law) 
• 
Geography-specific regulatory authorities (if regulatory approval is required)  
• 
An independent medical ethics committee or institutional review board. 
Similarly, approval of subsequent revisions to the CIP is required at each study center 
from the above mentioned groups prior to implementation of the revised CIP at that 
center. 
 
6. METHODOLOGY 
 
The study comprises two phases. The first phase through 6-month follow-up has the 
purpose to investigate use of the ECG Belt Research System to help choose pacing site, 
vector and pacing programming. 
The second phase of the study from 6 to 9 months follow-up has the purpose to further 
investigate use of the ECG Belt Research System for more personalized programming 
at follow-ups. 
 
a. Primary Objective 
Demonstrate benefit of using the ECG Belt Research System on reducing LVESV 
from baseline to 6 months post-implant compared to standard CRT. 
 

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b. Ancillary Objectives 
 
1. To estimate the benefit of using the ECG Belt Research System on LVEF 
compared to standard CRT. 
2. To estimate the benefit of using the ECG Belt Research System on change in 
quality of life compared to standard CRT. 
3. To estimate the benefit of using the ECG Belt Research System on change in 
Six-Minute Walk Test distance compared to standard CRT. 
4. To estimate the benefit of using the ECG Belt Research System on the Clinical 
Composite Score compared to standard CRT. 
5. To characterize ECG Belt Research System-related AEs. 
6. To assess the changes in LVESV from 6-9 months between subjects who have 
and have not used the ECG Belt Research System at 6 months. 
7. To assess the extent of ECG Belt Research System guided programming 
changes across study visits. 
 
c. Subject selection criteria and enrollment 
Patients will be screened to ensure they meet all of the inclusion and none of the 
exclusion criteria prior to study enrollment. Ethics Committee approval of the ECG Belt 
CIP and Informed Consent Form (ICF) must be obtained prior to enrolling patients in the 
study. The patient is considered enrolled upon signing of the ICF. 
i. Inclusion criteria 
• Indicated for CRT, with QRS duration ≥130 ms, and planned to be implanted 
with a market-released Medtronic CRT device with AdaptivCRT and a 
Medtronic quadripolar LV lead. 
• Meets at least one of the following criteria: 
o QRS duration < 150 ms 
o Prior documented Myocardial Infarction 
o Non-LBBBb 
• 
LVEDD ≥ 55 mm, as determined by site 
 
ii. 
Exclusion criteria  
• Permanent/persistent AF or presenting with AF 
• Pre-existing or previous LV lead or other confounding devices e.g. Left 
Ventricular Assist Device, Vagal Nerve Stimulator 
• Currently implanted with IPG or ICD with > 10% RV pacing  
• Permanent complete AV block 
• Enrolled in a concurrent study that may confound the results of this study. Pre-
approval from the study manager is required for enrollment of a patient that is 
in a concurrent study. 
• Less than 1 year life expectancy 
• Vulnerable adults 
• Younger than 18 years of age 
                                                 
b Does not meet Strauss definition of LBBB1: QS or rS in leads V1 and V2 and Mid-QRS notching 
or slurring in ≥2 of leads V1, V2, V5, V6, I, and aVL 

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d. Randomization 
Eligible subjects will be randomized 2:1:1 to either the ECG Belt arm, control arm A, or 
control arm B respectively. The latter two arms are identically treated up until the 6-
month follow-up and will be called the control arm as a whole. Randomization schedules 
will be created for each site by a statistician using randomized blocks and stratified by 
center to ensure relatively equal randomization within each center.  
After verification that a subject meets all inclusion/exclusion criteria and core lab 
confirmation that LVESV is able to be determined from the subject’s echocardiogram, 
subjects will undergo randomization prior to any implant attempt. Centers will receive 
each subject’s assignment electronically via the study database. 
e. Blinding 
Due to the use of the ECG Belt during implant and follow-up, it is difficult to blind 
subjects or physicians to the treatment assignment. The echo core lab will be blinded to 
the randomization assignment. 
f. Minimization of Bias 
Selection of subjects, treatment of subjects, and evaluation of study data are potential 
sources of bias. Methods incorporated in the study design to minimize potential bias 
include (but are not limited to): 
• 
Subjects will be screened to confirm eligibility for enrollment with defined 
inclusion/exclusion criteria prior to enrollment.  
• 
A maximum of 40 subjects is allowed to be randomized at a single center. 
• 
Subject demographics and other characteristics will be collected at 
baseline to evaluate any possible differences between ECG Belt and 
control groups that may affect outcome.  
• 
All clinicians will be trained and required to follow the CIP. 
• 
Clinicians will be encouraged to approach all subjects who meet 
inclusion/exclusion criteria. 
• 
The primary endpoint, LVESV is a measurement that is not directly 
controlled by the subject, making it less prone to bias due to placebo 
effects. 
• 
Individual randomization assignments will only be provided to centers 
once required data is entered into the database. 
• 
The echo core lab will measure the primary endpoint and will be blinded 
to the randomization assignment and follow-up status. 
 
When using the ECG Belt Research System in control arm subjects for data collection 
only, clinicians will be blinded to the ECG Belt Software Application maps and metrics.  
For subjects in the Control arm, the ECG Belt Research System data will not be 
collected at Implant and will not be displayed at Post-Implant Follow-up Visits and at the 
6 month Follow-up Visit (Control Arm B).  In these cases, Investigators will use their 
standard of care procedure for implant and device programming.  This will prevent the 

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ECG Belt Research System data from influencing their routine decision-making process 
for implant and device programming. Potential sources of bias that may be encountered 
in this clinical study have been considered and minimized by careful study design. 
 
7. STUDY PROCEDURES 
Prior to performing study related procedures, all sites must have Ethics Board/IRB/MEC 
and associated regulatory authority approval if applicable (e.g., Competent Authority 
approval) as well as documentation from Medtronic of site readiness. 
a. Investigator / Investigation site selection 
All clinical investigators managing the subject’s heart failure must be qualified 
practitioners and experienced in the diagnosis and treatment of subjects with heart 
failure. All EP/implanting physicians must be experienced and/or trained in the handling 
of CRT devices. 
The role of the principal investigator is to implement and manage the day-to-day conduct 
of the clinical investigation as well as to ensure data integrity and the rights, safety and 
well-being of the subjects involved in the clinical investigation. 
The principal investigator shall: 
• 
Be qualified by education, training, and experience to assume responsibility for 
the proper conduct of the clinical investigation 
• 
Be experienced/interested in CRT optimization 
• 
During implant, be willing to move the LV lead to a second location (if available 
and accessible) if the ECG Belt Research System does not indicate an 
improvement at the first location 
• 
Disclose potential conflicts of interest, including financial, that interfere with the 
conduct of the clinical investigation or interpretation of results (all geographies) 
The principal investigator shall be able to demonstrate that the proposed investigational 
site: 
• 
Has a reasonable number of eligible subjects within the recruitment period 
• 
Has a coordinator, a qualified investigational site team and adequate facilities for 
the foreseen duration of the clinical investigation 
Center personnel training will be completed prior to participation in this clinical study. 
 
b. Site activation  
During the activation process (prior to subject enrollment), Medtronic will train site 
personnel on the ECG Belt Research System, clinical investigation plan, relevant 
standards and regulations, if needed, informed consent, and on data collection and 
reporting tools. If new members join the study center team, they will receive training on 
the applicable clinical study requirements relevant to their role before contributing to the 
clinical study. 

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Medtronic contracts with participating institution/investigators through a Clinical Trial 
Agreement that defines the scope and responsibilities and associated compensation 
related to carrying out the obligations under a clinical study sponsored by Medtronic. 
Prior to performing study related activities, all local regulatory requirements shall be 
fulfilled, including, but not limited to the following:  
• 
Ethics Committee approval (and voting list, as required by local law) of the 
current version of the CIP and ICF  
• 
Regulatory authority approval or notification (as required per local law)  
• 
Fully executed Clinical Trial Agreement (CTA)  
• 
Curriculum Vitae (CV) of investigators (all geographies), and key members 
of the investigation site team (Europe) 
o The signature on the CV must be dated within 3 years prior to the 
date of activation of the site (Europe). 
• 
Documentation of delegated tasks 
• 
Documentation of study training  
Additional requirements imposed by the Ethics Committee and regulatory authority shall 
be followed, if appropriate.  
In addition, all participating site staff must be trained on the current version of the CIP 
and must be delegated by the principal investigator prior to performing study related 
activities. Personnel delegated to operate the ECG Belt Research System and perform 
the implant and/or provide technical support at implant and follow-up must be trained on 
the use of the ECG Belt Research System.  
Medtronic will provide each study center with documentation of study center/investigator 
readiness; this letter must be received prior to subject enrollment. 
 
c. Equipment requirements 
The following equipment must be available at each center to support study activities: 
• 
Medtronic will provide an ECG Belt Research System and an adequate 
supply of disposable ECG Belts to each center 
• 
Echocardiographic system  
• 
Any market-released Medtronic programmer and analyzer can be used, for 
example CareLink Model 2090 Programmer with the Model 2290 Analyzer.  
• 
Medtronic will provide cables and adaptors necessary to test leads with the 
Analyzer during implant 
• 
Medtronic will provide disposable tape measures to collect chest 
circumference at the Baseline visit 
No arrangements are needed related to the calibration and maintenance of the 
Medtronic-provided ECG Belt Research System. The echocardiographic system will be 
calibrated and maintained per hospital policy. 
 

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d. Data collection 
Data collection requirements are summarized in Table 2 below. 
 
Table 2:  Data collection and study procedure requirements at subject visits 
Study Procedure Baseline Rando-
mization 
Implant 
Post-implant 
Follow-up 
6-month 
Follow-up 
9-month 
Follow-up 
Patient informed 
consent 
x 
 
 
 
 
 
Inclusion/exclusion 
assessment 
x 
 
 
 
 
 
Medical history and 
demographics 
x 
 
 
 
 
 
NYHA Functional 
Classification 
x 
 
 
 
x 
x 
Minnesota living 
with Heart Failure 
questionnaire 
x 
 
 
 
x 
x 
Patient Global 
Assessment Score* 
 
 
 
 
x 
x 
Six-Minute Walk 
Test 
x 
 
 
 
x 
 
Echocardiogram 
x** 
 
 
 
x 
x 
Randomization 
 
x 
 
 
 
 
Collection of CRT 
implant 
characteristics and 
implanted system 
description 
 
 
x 
 
 
 
ECG Belt Research 
System procedure 
 
 
ECG Belt 
arm: 
management 
ECG Belt 
arm: 
management 
 
Control arm 
A and B: 
blinded data 
collection 
ECG Belt 
arm and 
Control 
arm A: 
manage-
ment 
 
Control 
arm B: 
blinded 
data 
collection 
All 
subjects: 
unblinded 
data 
collection 
ECG 12 lead 
x*** 
 
 
 
 
 
Full CRT device 
interrogation and 
save-to-media 
 
 
At end of visit Pre and post-
visit 
Pre and 
post-visit 
Pre and 
post-visit 
Exits 
 
 
As they occur 
 
 
Adverse events 
(AEs, including 
AEs with outcome 
of death, and 
hospitalizations) 
Device 
deficiencies**** 

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Study Procedure Baseline Rando-
mization 
Implant 
Post-implant 
Follow-up 
6-month 
Follow-up 
9-month 
Follow-up 
System 
modifications 
Study deviations 
* This is needed for Clinical Composite Score 
** Echo is acceptable if taken within 2 months of enrollment 
*** 12-lead ECG is acceptable if taken within 30 days of enrollment 
**** Where “device” refers to the ECG Belt Research System used in this study 
 
 
e. Role of the sponsor representatives 
Sponsor representatives may provide support as required for the study under 
supervision of the Principal Investigator, including: 
• 
Provide study training relevant and pertinent to the involvement of personnel 
conducting study activities and investigator responsibilities 
• 
Technical support at baseline, implant and follow-up visits under the 
supervision of a study investigator, but no data entry into the electronic 
database shall be performed by Medtronic personnel at sites. Medtronic 
personnel may support completion of the study worksheets. 
 
f. Patient informed consent process 
The ICF is defined as a legally effective documented confirmation of a patient’s voluntary 
agreement to participate in a particular clinical study after information has been given to 
the patient on all aspects of the clinical study that are relevant to the patient’s decision to 
participate. This process includes obtaining an ICF and an Authorization to Use and 
Disclose Personal Health Information/Research Authorization/other privacy language as 
required by law (US sites) that has been approved by the study center’s Ethics 
Committee and signed and dated by the subject. A patient may only consent after 
information has been given to the patient on all aspects of the clinical investigation that 
are relevant to the subject’s decision to participate. Patients requiring a Legally 
Authorized Representative to consent should not be enrolled in the ECG Belt study.  
Consistent with the Declaration of Helsinki, vulnerable adults (i.e. those patients mentally 
incapable of giving consent) are excluded from this protocol. Any patients with mental 
incompetence (e.g. Alzheimers, dementia, psychiatric disorders, developmental 
disorders) should be assessed for vulnerable status. This protocol defines vulnerable 
adult as those patients mentally incapable of giving consent, in the Investigator’s 
opinion. The Investigator should consider the definition of vulnerable adult per ISO 
14155, which defines vulnerable adults as: “vulnerable patients are those patients that 
could be unduly influenced by the expectation or benefits associated with participation or 
of retaliatory response from senior members of a hierarchy in case of refusal to 
participate.  For example, this could include Individuals with loss of autonomy due to 
immaturity or through mental disability, persons in nursing homes, children, 
impoverished persons, subjects in emergency situations, ethnic minority groups, 
homeless persons, nomads, refugees, and those incapable of giving informed consent. 
Other vulnerable subjects could include, for example, members of a group with a 
hierarchical structure such as university students, subordinate hospital and laboratory 

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personnel, employees of the sponsor, members of the armed forces, and persons kept 
in detention.” 
 
Prior to enrolling patients, each center’s Ethics Committee will be required to approve 
the ICF. The document(s) must be controlled (i.e. versioned and/or dated) to ensure it is 
clear which version(s) were approved by the Ethics Committee. Any adaptation of the 
sample ICF must be reviewed and approved by Medtronic and the Ethics Committee 
reviewing the application prior to enrolling subjects.  
The investigator must notify the subject of any significant new findings about the study 
that become available during the course of the study which are pertinent to the safety 
and well-being of the subject, as this could impact a subject’s willingness to participate in 
the study. If relevant, approval may be requested from subjects to confirm their 
continued participation. 
Prior to initiation of any study-specific procedures, patient informed consent must be 
obtained from the subject. Likewise, privacy or health information protection regulation 
may require subjects to sign additional forms to authorize centers to submit subject 
information to the study sponsor. The informed consent process must be conducted by 
the principal investigator or an authorized designee, and the Patient Consent Form and 
Authorization to Use and Disclose Personal Health Information/Research 
Authorization/other privacy language (US) must be given to the subject in a language 
he/she is able to read and understand. The process of patient informed consent must be 
conducted without using coercion or undue improper influence on or inducement of the 
subject to participate by the investigator or other center personnel. The informed consent 
process shall not waive or appear to waive subject’s legal right. The language used shall 
be as non-technical as possible and must be understandable to the subject and the 
impartial witness, where applicable.  
The subject must have ample time and opportunity to read and understand the informed 
consent form, to inquire about details of the study, and to decide whether or not to 
participate in the clinical study. All questions about the study should be answered to the 
satisfaction of the subject. 
When the patient decides to participate in the clinical study, the ICF must be signed and 
personally dated by the patient and investigator or authorized designee, as required by 
the ICF. If applicable, the witness shall also sign and personally date the ICF to attest 
that the information in the ICF was accurately explained and clearly understood by the 
subject, and that informed consent was freely given. 
A copy of the ICF and the Authorization to Use and Disclose Personal Health 
Information/Research Authorization/other privacy language (US), signed and dated as 
required by law, must be provided to the subject.  
If the ICF is obtained the same day the subject begins participating in study-related 
procedures, it must be documented in the subject’s case history that consent was 
obtained prior to participation in any study-related procedures. It is required for the 
informed consent process to be documented in the patient’s case history, regardless of 
circumstance. 
In the event the patient cannot read and/or write, witnessed (impartial third party) patient 
informed consent will be allowed, provided detailed documentation of the process is 
recorded in the patient’s case history and the witness signs and dates the patient 
informed consent. The independent witness shall be present throughout the process. 

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The written informed consent form and any other information shall be read aloud and 
explained to the patient. The patient should “make his mark” (sign or otherwise 
physically mark the document so as to indicate consent) on the ICF as well. The ICF 
should document the method used for communication with the prospective subject and 
specific the means by which the prospective subject communicated agreement to 
participate in the study.  
The original of the signed ICF must be filed in the hospital/clinical chart and/or with the 
subject’s study documents.  
The ICF and Authorization to Use and Disclose Personal Health Information/Research 
Authorization/other privacy language as required by law (US) must be available for 
monitoring and auditing. Any Medtronic Field personnel who support the ECG Belt study 
must be able to review the subject’s signed and dated Consent Form and verify its 
completeness prior to proceeding with the implant/download. In the event the Medtronic 
Field personnel identify patient informed consent as being incomplete, the study specific 
procedures will not be allowed to occur until the consent of the patient can be 
adequately and appropriately obtained. 
When a patient and the principal investigator or authorized designee, as required have 
personally signed and dated the ICF, the patient is considered a subject enrolled in the 
study. The date the subject signed the ICF and data protection authorization must be 
documented in the subject’s medical records.  
 
g. Baseline (pre-CRT implant) data collection 
Prior to implant the following information is required to be collected at the baseline visit: 
• 
Echo recording. Instructions on data transmission to Core Lab will be 
provided under a separate cover. The echo should be current within the last 
2 months of the enrollment date. All echos must be anonymized and 
labeled with a Medtronic-assigned identification number prior to submission 
to the Core Lab. 
• 
Baseline ECG (12-lead). The ECG should be current within last 30 days of 
the enrollment date. 
• 
NYHA Functional Classification 
• 
Minnesota Living with Heart Failure questionnaire 
• 
Six-Minute Walk Test 
• 
Medical history and demographics 
An echo will be collected prior to randomization. A standard of care echo is acceptable if 
taken within 2 months of enrollment. The echo will be sent to the core laboratory for 
review. The core lab review of the baseline echo will be required to confirm readability of 
LVESV. If the images are determined unreadable and/or of poor quality by the core lab, 
the site may try another echo or exit the subject from the study prior to randomization. 
Additionally, a 12-lead ECG will be collected if no 12-lead ECG has been performed 
within 30 days of enrollment. For subjects being considered for an upgrade from 
pacemaker/ICD, their rhythm will be tested.  For subjects with a single chamber device, 
program to VVI 40. For subjects with a dual chamber device, program to AAI mode or 
extend the AV delays to the maximum setting. If the subject receives ventricular pacing 
from the device under the setting, the subject will be exited from the study. 

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h. Randomization 
Centers will receive each subject’s randomization assignment electronically via the 
Oracle Clinical database upon confirmation of the subject’s inclusion/exclusion criteria 
and baseline echo readability. 
 
i. Implant 
Use of market released Medtronic CRT device with AdaptivCRT and a market released 
Medtronic quadripolar LV lead is required. 
Physicians are expected to follow the recommendations of the 2012 EHRA-HRS expert 
consensus statement19. These recommendations include “venography to evaluate 
candidate venous tributaries and consideration of electrical and fluoroscopic methods to 
help select optimal sites; The final position of the LV pacing lead depends on the 
anatomy of the cardiac venous system, the performance and stability of the pacing lead, 
and the absence of PNS [Phrenic Nerve Stimulation]”. Furthermore, the consensus also 
states that “recent trials evaluating long-term response to CRT show a good clinical 
response with a range of LV lead locations”. 
The following information is required to be collected at the implant visit: 
• 
CRT implant characteristics and implanted system details 
• 
For control arms A and B, methods used to determine LV lead placement 
and programming settings 
• 
For subjects randomized to the ECG Belt arm, ECG Belt Research System 
data will be collected for the following situations: 
o intrinsic rhythm  
o during intra-procedural biventricular pacing  
o final device programming 
• 
A full interrogation of the implanted device with final programmed 
parameters. 
 
In case the final implanted system differs from what was planned according to the 
inclusion criteria (a market-released Medtronic CRT device with AdaptivCRT and a 
Medtronic quadripolar LV lead), continue to collect data and follow the protocol as 
closely as possible. 
i. 
ECG Belt arm: CRT device implant and recommended programming 
For subjects enrolled in the ECG Belt arm of the study, the ECG Belt will be applied on 
the subject’s chest and back just before he or she is prepped for the CRT implant 
procedure. The right heart leads should be implanted per standard of care. After 
evaluation of a venogram, the quadripolar LV lead will be placed in the implanter’s 
preferred site. The ECG Belt Research System will obtain measurements of the baseline 
intrinsic rhythm and during pacing.  
If the ECG Belt Software Application does not indicate an improvement in electrical 
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stimulation, it is recommended that the implanter move the lead to another candidate 
site (e.g. other vein or side branch) if such a site is available and accessible. An 
improvement in dyssynchrony will be considered a relative improvement in SDAT by 
≥10% with pacing or an improvement in LVAT by ≥30% without a worsening of SDAT by 
more than 10%. If the lead is placed at another location, the ECG Belt Research System 
measurements will be repeated during pacing at available electrodes in this new site.  
The final LV lead implant site will be determined by the maximum resynchronization 
effect achieved as long as it satisfies other clinical criteria for lead placement 
(reasonable pacing thresholds, lack of phrenic nerve stimulation at target LV pacing 
site(s), anatomic stability of lead location) per physician discretion.   
After the CRT device is implanted and the pocket is closed per standard of care, the LV 
pacing vector is expected to be programmed to provide the best electrical 
resynchronization, as indicated by the ECG Belt Software Application, after clinical 
factors such as phrenic nerve stimulation, reasonable pacing thresholds, etc. have been 
considered. AdaptivCRT and multiple point pacing (MPP) should be OFF. MPP is 
intended for non-responders who cannot be identified at implant. Additionally, MPP 
results in a decrease to longevity that may be avoided with the personalized 
programming offered by the ECG Belt system.  
Upon completion of the CRT implant procedure, the ECG Belt Software Application 
results will be saved and submitted to Medtronic, the System will be disconnected, and 
the ECG Belt will be removed from the subject.  
See Figure 2 for an overview of the study workflow at implant for subjects in the ECG 
Belt arm. 
ii. 
Control arms A and B: CRT device implant and programming  
For subjects in control arms A and B, the final position of the LV pacing lead must be 
determined per physician routine standard of care. 
The LV pacing vector and other CRT settings must be programmed per physician 
routine standard of care.  
AdaptivCRT and MPP should be OFF. MPP is intended for non-responders who cannot 
be identified at implant. Additionally, MPP results in a decrease to longevity that may be 
avoided with the personalized programming offered by the ECG Belt system. 

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Figure 2: ECG Belt management workflow diagram at Implant 
 
Place RA, RV Leads per standard of care
Place LV lead in preferred site upon 
evaluation of venogram
Place defib patches and
ECG Belt, connect System,
check System status
≥10% SDAT 
improvement while 
pacing?
Pace at available 
electrodes
and measure 
dyssynchrony
Move LV lead to  
alternate site 
(recommended if 
available)
No
Measure 
dyssynchrony of 
intrinsic (unpaced) 
rhythm
Fixate LV lead and 
finish implant
AdaptivCRT OFF
Yes
Save report, disconnect 
System, and remove 
ECG Belt 
Evaluate system 
summary view for 
tested electrodes and 
site(s)
Recommended 
Programming: vector 
suggested by ECG Belt 
(considering PNS, 
thresholds etc.)
Run VectorExpress to 
determine the optimal 
anode for each cathode and 
measure dyssynchrony for 
the four cathodes 
≥30% LVAT 
improvement while 
pacing?
 SDAT worsened by 
more than 10%  
while pacing?
No
Yes
No
Yes

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j. Scheduled Follow-up Visits 
After receiving electronic notice of implant in the Oracle Clinical database, the database 
system will provide the windows for each visit. Should a subject miss a visit or the visit 
fall outside the pre-specified window, a study deviation must be reported and the original 
follow-up schedule maintained for subsequent visits.  
Data analyses will include follow-up visits, regardless of whether the visit occurs within 
the window. Therefore, a late visit is preferred over a missed visit but must be 
accompanied by a deviation. Follow-up visit windows are listed in Table 3 and are based 
on days post-implant. 
Table 3:  Data collection and study procedure requirements at subject visits 
Study Follow-up 
Visit 
Window 
(Calculated days post-implant) 
Window Start 
(days post-implant) 
Window End 
(days post-implant) 
Post-Implant follow-up 
0 
14 
6-month Follow-up 
182 
196 
9-month Follow-up 
274 
288 
 
 
k. Post-Implant Follow-Up 
 
The following information is required to be collected at post-implant follow-up. This can 
be pre-discharge after the CRT implant or a standalone visit, whichever aligns best with 
standard CRT practice at each site: 
• 
A full interrogation of the implanted device with programmed parameters at 
start of visit (save to media) 
• 
All subjects will require the ECG Belt to be temporarily applied to the chest 
and back. A separate ECG Belt is suggested to be used for the Implant and 
Post-Implant workflows to ensure consistent application conditions in the 
Post-Implant workflow.  If the Post-Implant Follow-up visit occurs on the 
same day as Implant and the same ECG Belt will be used, ensure the 
signal quality does not diminish compared to Implant and that the total wear 
time does not exceed 8 hours.  Use a new ECG Belt if these conditions 
cannot be met. 
• 
For the ECG Belt arm, ECG Belt Research System data will be collected 
without pacing (e.g. intrinsic rhythm) and with pacing with a subset of 
vectors and various pacing parameters in order to manage CRT therapy 
(see Figure 3 for the workflow, details will be provided in the Case Report 
Forms (CRFs) and in a controlled handbook).  
• 
For control arms A and B, ECG Belt Research System data will be collected 
without pacing (e.g. intrinsic rhythm) and at final programming settings. 
Pacing configurations, A-V and V-V delays will be temporarily programmed 
to collect blinded ECG Belt Research System data, data collection is 
optional.  These data will not be used to determine the final programming 
settings. 

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• 
Control arms A and B: methods used to determine programming settings 
will be collected. 
• 
A full interrogation of the implanted device with programmed parameters at 
end of visit (save to media) 
i. 
ECG Belt arm: Post-Implant Follow-Up CRT programming 
The ECG Belt arm will require ECG Belt Research System management. 
Changes in dyssynchrony will be measured with AdaptivCRT Bi-V + LV, 
AdaptivCRT Bi-V and more personalized A-V and/or V-V delays. The optimal LV 
pacing vector will also be reassessed. 
Adaptive LV-only pacing, as provided by AdaptivCRT BiV + LV ON has been 
shown to improve clinical outcome20. However, patients included in this study 
may benefit from a more personalized, ECG Belt Research System-guided A-V 
and/or V-V delays that maximally decrease dyssynchronyc.  
The recommended programming will be determined by the relative change in 
ECG Belt Research System metrics while pacing compared to the intrinsic 
rhythm. 
Recommendations for using an ECG Belt Research System guided A-V and/or 
V-V delay or AdaptivCRT Bi-V settings: 
1) >15% improvement in SDAT with AdaptivCRT BiV+LV ON 
AdaptivCRT BiV+LV is recommended be programmed ON unless an 
ECG Belt suggested personalized A-V and/or V-V setting or 
AdaptivCRT Bi-V setting have an additional SDAT improvement of at 
least 10%. For example, if AdaptivCRT BiV+LV ON offers an 18% 
improvement in SDAT, a personalized A-V and/or V-V setting should 
have at least a 28% improvement in SDAT to be used instead of 
AdaptivCRT BiV+LV. 
2) 0-15% improvement in SDAT with AdaptivCRT BiV+LV ON 
AdaptivCRT BiV+LV is recommended be programmed ON unless an 
ECG Belt suggested A-V and/or V-V setting or AdaptivCRT Bi-V 
settings offer an additional 5% absolute improvement in SDAT. 
3) The SDAT with AdaptivCRT is worse than the intrinsic SDAT  
When no improvement in SDAT can be achieved with AdaptivCRT 
BiV+LV ON, the ECG Belt suggested A-V and/or V-V setting or 
AdaptivCRT Bi-V-like settings with the best SDAT are recommended. 
The recommended programming settings account for potential variability in 
SDAT measurements and favor AdaptivCRT over standard BiV CRT because it 
may be associated with additional improvement in clinical response compared 
with standard CRT21.   
The recommended LV pacing vector will be the vector that provides the 
maximum resynchronization based on the ECG Belt Research System metrics, 
after consideration of other clinical factors (phrenic nerve stimulation, pacing 
                                                 
c Note: The V-V delay is not programmable in some currently available versions of AdaptivCRT. 
This capability will be added in the future. 

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thresholds, etc.). MPP should be OFF. MPP is intended for non-responders who 
cannot be identified at the post-implant follow-up. Additionally, MPP results in a 
decrease to longevity that may be avoided with the personalized programming 
offered by the ECG Belt system. 
Once study testing is complete, the ECG Belt Research System results will be saved 
and submitted to Medtronic, the System will be disconnected, and the ECG Belt will be 
removed from the subject. 
 
See Figure 3 for an overview of the ECG Belt management workflow and recommended 
programming at Post-Implant follow-up for subjects in the ECG Belt arm. 
 
 

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Figure 3: ECG Belt management workflow and recommend programming at Post-
Implant Follow-Up 
Place ECG Belt, connect 
System, check System status
Measure dyssynchrony 
of intrinsic (unpaced) 
rhythm
Measure dyssynchrony 
with AdaptivCRT Bi-V + 
LV, AdaptivCRT BiV, and 
personalized AV and VV 
delays 
>15% SDAT
improvement with 
AdaptivCRT BiV + LV ON?
Recommended Programming: 
AdaptivCRT BiV + LV ON, 
vector suggested by ECG Belt 
(considering PNS, thresholds etc.) 
Best BiV setting is 
10% better than 
AdaptivCRT BiV + LV ON? 
>0-15% SDAT 
improvement with 
AdaptivCRT BiV + LV ON?
0% or worse SDAT 
with AdaptivCRT BiV + LV 
ON?
Best BiV setting is
5% better than 
AdaptivCRT BiV + LV ON? 
Yes
No
No
Yes
Yes
Recommended Programming: 
best BiV setting, 
vector suggested by ECG Belt 
(considering PNS, thresholds etc.) 
Yes
Yes
No
No
Save report, disconnect System, 
remove ECG Belt
Is aCRT BiV + LV an ECG 
Belt suggested setting?
No
Yes
Run VectorExpress to determine 
the optimal anode for each 
cathode and measure 
dyssynchrony for the four 
cathodes 
 
 
ii. 
Control arms A and B:  Post-Implant Follow-Up CRT programming 
For subjects in the control arms, the ECG Belt Research System data is collected 
blinded and not visible for the physician or operator. Once study testing is complete, the 
ECG Belt Research System results will be saved and submitted to Medtronic, the 
System will be disconnected, and the ECG Belt will be removed from the subject. 
 

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The LV pacing vector and other CRT settings will be programmed per the physician’s 
routine standard of care.  Pacing configurations, A-V and V-V delays will be temporarily 
programmed to collect blinded ECG Belt Research System data, data collection is 
optional.  These data will not be used to determine the final programming settings.  
AdaptivCRT and MPP should be OFF. MPP is intended for non-responders who cannot 
be identified at the post-implant follow-up. Additionally, MPP results in a decrease to 
longevity that may be avoided with the personalized programming offered by the ECG 
Belt system. 
 
See Figure 4 for an overview of the ECG Belt data collection workflow for subjects in 
control arm A and B. 
 
 
Figure 4: Blinded ECG Belt data collection workflow diagram at Post-implant and 6 
Months Follow-Ups 
Place ECG Belt, connect System, 
start ECG Belt Software in 
blinded mode
Measure dyssynchrony 
of intrinsic (unpaced) 
rhythm
Measure dyssynchrony at 
final programmed settings as 
determined by routine care
Save report, disconnect 
System, remove ECG 
Belt
 
 
l. 6-Month Follow-up Visit 
 
The following information is required to be collected at the 6-month follow-up visit: 
• 
Echocardiogram images with CRT on (should be taken prior to ECG Belt 
use). All echos must be anonymized and labeled with a Medtronic-assigned 
identification number prior to submission to the Core Lab. 
• 
NYHA Functional Classification 
• 
Patient Global Assessment Score 
• 
Minnesota Living With Heart Failure questionnaire  
• 
Six-Minute Walk Test 
• 
A full interrogation of the implanted device with programmed parameters at 
start of visit (save to media) 
• 
All Subjects will require the ECG Belt to be temporarily applied to the chest 
and back. 
• 
For the ECG Belt arm and control arm A, ECG Belt Research System data 
will be collected without pacing (e.g. intrinsic rhythm) and with pacing with a 
subset of vectors and various pacing parameters in order to manage CRT 
therapy (see Figure 5 for the workflow, further details will be provided in the 
CRFs and in a controlled handbook). 

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• 
For control arm B, ECG Belt Research System data will be collected only 
without pacing (e.g. intrinsic rhythm) and at final programming settings.  
Pacing configurations, A-V and V-V delays will be temporarily programmed 
to collect blinded ECG Belt Research System data, data collection is 
optional.  These data will not be used to determine the final programming 
settings. 
• 
For control arm B, methods used to determine programming settings will be 
collected 
• 
A full interrogation of the implanted device with programmed parameters at 
end of visit (save to media) 
i. 
ECG Belt arm and control arm A:  6 month follow-up CRT programming 
The ECG Belt arm and control arm A will require ECG Belt Research System 
management. From 6 to 9 months the ECG Belt Research System will be used to further 
investigate personalized programming. Changes in dyssynchrony will be measured with 
AdaptivCRT BiV + LV ON, AdaptivCRT Bi-V-like settings, and selected A-V and V-V 
delays (see Figure 5 for the workflow and programming recommendations). This may 
further optimize pacing vector and pacing parameters, especially if there are parameters 
that provide a distinctively large improvement in resynchronization compared to the 
pacing parameters/settings to which the patient was programmed before the follow-up.  
 
Once study testing is complete, the ECG Belt Research System results will be saved 
and submitted to Medtronic, the System will be disconnected, and the ECG Belt will be 
removed from the subject. 
 
 
 
Figure 5: ECG Belt management workflow and programming recommendations at 6 
Months Follow Up 
Place ECG Belt, connect 
System, check System status
Measure dyssynchrony 
of intrinsic (unpaced) 
rhythm
Run VectorExpress to determine 
the optimal anode for each 
cathode and measure 
dyssynchrony for the four 
cathodes 
Measure dyssynchrony 
with AdaptivCRT Bi-V + 
LV ON and other pacing 
settings 
Recommended 
programming: settings 
suggested by ECG Belt 
workflow 
Save report, disconnect System, 
remove ECG Belt
 
 

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ii. 
Control arm B:  6 month follow-up CRT recommended programming 
For subjects in the control arm B, the ECG Belt Research System data is collected 
blinded and not visible for the physician or operator. Once study testing is complete, the 
ECG Belt Research System results will be saved and submitted to Medtronic, the 
System will be disconnected, and the ECG Belt will be removed from the subject. 
The LV pacing vector and other CRT settings will be programmed per physician’s routine 
standard of care. AdaptivCRT will be turned OFF.  Pacing configurations, A-V and V-V 
delays will be temporarily programmed to collect blinded ECG Belt Research System 
data, data collection is optional.  These data will not be used to determine the final 
programming settings. 
See Figure 4 for an overview of the ECG Belt data collection workflow for subjects in 
control arm B. 
m. 9-Month Follow-up Visit 
 
The following information is required to be collected at the 9 month follow-up visit: 
• 
Echocardiogram images with CRT on (should be taken prior to ECG Belt 
use). All echos must be anonymized and labeled with a Medtronic-
assigned identification number prior to submission to the Core Lab. 
• 
NYHA Functional Classification 
• 
Patient Global Assessment Score 
• 
Minnesota Living With Heart Failure questionnaire  
• 
A full interrogation of the implanted device with programmed parameters 
at start of visit (save to media) 
• 
All subjects will require the ECG Belt to be temporarily applied to the 
chest and back.  ECG Belt Research System data will be collected 
without pacing (e.g. intrinsic rhythm), with AdaptivCRT BiV LV ON, and 
for selected pacing settings (see Figure 6 for the workflow). 
• 
Once ECG Belt Research System data has been collected, all 
programming will occur per physician discretion 
• 
A full interrogation of the implanted device with programmed parameters 
at end of visit (save to media) 
• 
Make sure that a final status of any open Adverse Events is collected  
• 
After the visit the subject is considered exited from the study 
 

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Figure 6: ECG Belt data collection workflow diagram at 9 Months Follow-Up 
Place ECG Belt, connect 
System, check System status
Measure dyssynchrony 
of intrinsic (unpaced) 
rhythm
Run VectorExpress to determine 
the optimal anode for each 
cathode and measure 
dyssynchrony for the four 
cathodes 
Measure dyssynchrony 
with AdaptivCRT Bi-V + 
LV ON and other pacing 
settings 
Programming per 
physician discretion
Save report, disconnect System, 
remove ECG Belt
 
 
n. Device Interrogation  
For implant and follow-up visits, an initial (not at implant) and final full “Interrogate ALL” 
final device interrogation file (pdd) must be obtained and saved in a digital format (e.g., 
USB). The original file will be stored at the site and a copy provided electronically to 
Medtronic. Device data should not be cleared at any time. In case a device interrogation 
file was not obtained on site, but the subject is remotely followed per standard of care, 
Medtronic may obtain remote CareLink files of that subject from the CareLink server if 
available for the follow-up period of the subject. 
o.  Healthcare Utilization 
Health Care Utilization information will be collected as part of the Adverse Event Form, if 
applicable. A hospitalization due to worsening heart failure will be determined by the site 
and defined as an event that occurred primarily because of the documented presence of: 
• 
Use of additional or increased pharmacologic or mechanical interventions 
directed at the treatment of heart failure including:  
o Initiation of intravenous diuretic, inotropic, or vasodilator therapy 
o Significant addition or increase in oral heart failure therapy 
o Up-titration of intravenous therapy, if already on therapy 
o Initiation of mechanical or surgical intervention (mechanical 
circulatory or ventilatory support, heart transplantation or ventricular 
pacing to improve cardiac function), or the use of ultrafiltration, 
hemofiltration, or dialysis that is specifically directed at treatment of 
heart failure. 
In addition, at least 1 of the following 2 criteria must be documented:  
• 
Clinical manifestations of heart failure including the following new or 
worsening signs or symptoms:   
o Dyspnea 
o Orthopnea 
o Paroxysmal nocturnal dyspnea 
o Edema 

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o Pulmonary rales 
o Jugular venous distension 
o New or worsening third heart sound or gallop rhythm 
o Hypotension or cardiogenic shock not occurring in the context 
of an acute myocardial infarction or as the consequence of an 
arrhythmia, or 
o Other clinical evidence of new or worsening heart failure, eg, 
weight gain, or confinement to bed predominantly due to heart 
failure symptoms 
 
• 
Biomarker or radiographic evidence consistent with heart failure 
o Biomarker results consistent with heart failure include documented 
increased or increasing levels of a natriuretic peptide (BNP or 
NTproBNP). 
o Radiographic evidence consistent with heart failure includes 
documented worsening pulmonary congestion or pulmonary edema 
on chest X-ray or other generally recognized imaging pattern. 
Hospitalizations due to worsening heart failure will also be confirmed by Medtronic and 
an attempt will be made to resolve any discrepancies with the site determination.  
p. System Modification 
A system modification will be reported in the event the device and/or leads require 
invasive modification (e.g., generator or lead explant, generator or lead replacement, 
lead repositioning) or CRT is turned off. In the event of a system modification, the follow-
up schedule for the subject will remain unchanged. For a system modification the 
following activities are required: 
• 
Perform a device interrogation before and after the system modification. 
• 
If the subject is in the ECG Belt arm, use the ECG Belt Research System to 
place the lead in a suitable pacing site (if applicable) and for device 
programming optimization.  
The reason for the system modification must be recorded on the CRF, including whether 
it was due to worsening heart failure, treatment failure, or lack of/insufficient therapeutic 
response. 
If the device is taken out of service (e.g. explanted or capped) and a replacement will not 
be implanted, keep the subject in the study and collect data as scheduled through the 6 
month visit. ECG Belt Research System data collection at 6 months is optional. After the 
6 month visit, subjects with an out of service device should be exited from the study. 
All explanted product (device, leads, etc.) should be returned to Medtronic for analysis 
when permissible by local laws and regulations.  
In the event that a subject has a re-attempt after a previous unsuccessful system 
modification, the subsequent attempt(s) must be reported via CRF as separate system 
modifications. 
 
q. Study Exit 
Once the 9-month follow-up is completed, the subject is considered exited from the 
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planned. No exit CRF is required. The exit date is collected on the 9-month visit CRF. No 
data should be collected after the 9-month follow-up, except for updates and resolutions 
to AEs that started during or prior to the 9-month follow-up.  
A study exit CRF is required for all subjects exiting the study prior to the 9-month follow-
up, except in the case of death. Prior to exiting a subject from the study, it is 
recommended to follow the subject until all unresolved system related AEs are resolved 
or unresolved with no further actions planned. Following exit, subjects will continue to 
receive standard medical care. Upon exiting from the study, no further study data will be 
collected or study visits will occur for the subject. Investigators will request for 
permission to follow-up patients outside the clinical study in case of withdrawal due to 
problems related to investigational device safety or performance. 
Subjects are urged to remain in the study as long as possible but may be exited from the 
study for any of the following situations: 
• 
Subject lost to follow-up 
• 
Subject did not meet inclusion/exclusion criteria and was not randomized 
• 
Subject has unreadable echo at baseline (prior to randomization) 
• 
Subject did not provide consent or data use protection authorization 
• 
Subject implant not attempted 
• 
Subject implanted prior to being randomized 
• 
Subject chooses to withdraw (e.g., consent withdrawal, relocation to 
another geographic location)  
• 
Investigator deems withdrawal necessary (e.g., medically justified, 
inclusion/exclusion criteria not met, failure of subject to maintain adequate 
study compliance)  
The following information is required to be collected at study exit: 
• 
Reason for exit (indicated on CRF)  
• 
Date of study exit. This should be the date that data was last collected from 
the subject, including vital status 
• 
A full interrogation of the implanted device (save to media) (Except if lost to 
follow up or not yet implanted) 
• 
In the case that the subject is determined to be lost to follow-up, details of a 
minimum of two attempts and the method of attempt (e.g., one letter and 
one phone record or two letters) to contact the subject must be recorded. In 
addition, follow the regulations set forth by the governing Ethics 
Committee.  
 
r. Medications 
Medication data collection will be limited to collecting whether or not the subjects were 
on ACE/ARB, beta blockers, diuretics, and anti-arrhythmics at baseline. 
 

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8. INVESTIGATIONAL DEVICE/SOFTWARE STORAGE, 
HANDLING AND TRACEABILITY 
The ECG Belt Research System, with the exception of the tablet, is considered 
investigational in US, Canada, and Europe. The investigational system will be distributed 
to a center only when Medtronic has received all required documentation and has 
notified the center of center activation. Distribution of the investigational products to 
study centers during the clinical study will be managed by Medtronic and can only be 
ordered by Medtronic personnel. Investigational product, once received at the site, must 
be stored in a secure location at the site. It is the responsibility of the investigator to 
correctly handle, store, and track the investigational products maintained at the site. 
Investigational products will be used only in the study according to the CIP.  
In the future, a new version of the system may be incorporated that is market-approved 
in some geographies. In this case, investigational product distribution and tracking will 
only apply in geographies in which the product is investigational. 
A Device Disposition Log is available to the center in the Oracle Clinical database and 
will be used for tracking of all investigational ECG Belt Research System components 
provided by Medtronic during and after the study. The logs must be maintained at each 
study center and updated when an ECG Belt Research System component is received, 
opened (as applicable), (re)used, disposed of or returned to Medtronic. The disposition 
log tracks product information including, but not limited to: component name, serial 
number/lot number/batch number, date received from Medtronic, dates of use and 
subject identification, date returned to Medtronic, components not returned to Medtronic 
(if applicable), and name of person responsible for return or destruction/disposal (if 
applicable). Successfully used ECG Belts can be destroyed/disposed of according to 
local laws and regulations. Any ECG Belts that came into contact with a subject and 
were found deficient should be returned to Medtronic in a Medtronic-provided biohazard 
kit. Unused ECG Belts and reusable system components should be returned to 
Medtronic after the study. 
Medtronic will perform periodic reconciliation of investigational product to ensure 
traceability.  
 
9. STUDY DEVIATIONS 
A study deviation is defined as an event within a study that did not occur according to 
the Clinical Investigation Plan or the Clinical Trial Agreement. 
Investigators are not allowed to deviate unless it is necessary to protect the safety, rights 
or well-being of a subject in an emergency or in unforeseen situations beyond the 
investigator’s control (e.g. subject failure to attend scheduled follow-up visits, inadvertent 
loss of data due to computer malfunction, inability to perform required procedures due to 
subject illness). If nevertheless the investigator anticipates, contemplates, or makes a 
conscious decision to deviate, in other situations, Medtronic should be notified and 
asked for approval in advance.  
All study deviations must be reported on the Case Report Form regardless of whether 
medically justifiable, pre-approved by Medtronic, an inadvertent occurrence, or taken to 
protect the subject in an emergency. The explanation for the deviation must be 
documented. Multiple deviations of the same type at the same visit may be reported on 

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one case report form in the following situations: multiple device interrogations missing for 
same visit. In the occurrence of a corrupted device interrogation file, Medtronic may 
request a deviation to document that a readable interrogation file is unavailable. 
In the event the deviation involves a failure to obtain a subject’s consent, or is made to 
protect the life or physical well-being of a subject in an emergency, the deviation must be 
reported to the Ethics Committee as well as Medtronic within five (5) working days. 
Reporting of all other study deviations should comply with Ethics Committee policies 
and/or local laws and must be reported to Medtronic as soon as possible upon the 
center becoming aware of the deviation. Reporting of deviations must comply with Ethics 
Committee policies, local laws, and/or regulatory agency requirements. Refer to Table 9, 
Table 10 and Table 11 for Investigator Reports, geography-specific deviation reporting 
requirements and timeframes for reporting to Medtronic and/or regulatory bodies. 
Medtronic will review reported deviations on a periodic basis, assess their significance, 
and identify any additional corrective and/or preventive actions (e.g. amend the Clinical 
Investigation Plan, conduct additional training, and terminate the investigation). 
Repetitive or serious investigator compliance issues may result in initiation of a 
corrective action plan with the investigator and site, and in some cases, necessitate 
suspending enrollment until the problem is resolved or ultimately terminating the 
investigator's participation in the study. Medtronic will provide center-specific reports to 
investigators summarizing information on deviations that occurred at the investigational 
site on a periodic basis.  
Study deviation waivers for the Clinical Investigation Plan are prohibited. 
A study deviation is not required if additional data collection for the pacing 
configurations, A-V and V-V delays is not collected at the Control Post-Implant Follow-up 
visit and the 6 month Follow-up visit for Control B subjects.  
 
10. 
ADVERSE EVENTS AND DEVICE 
DEFICIENCIES 
Timely, accurate, and complete reporting and analysis of safety information for clinical 
studies are crucial for the protection of subjects. Reporting and analysis of safety data 
are mandated by regulatory authorities worldwide. Medtronic has established 
procedures in conformity with worldwide regulatory requirements to ensure appropriate 
reporting of safety information. This study is conducted in accordance with these 
procedures and regulations. 
For the ECG Belt study, AE CRF’s will be collected for all AEs that are potentially ECG 
Belt Research System-related and all serious AEs regardless of their relationship to the 
ECG Belt Research System and/or application procedure. 
a. Adverse Event and Device Deficiency definitions 
Where the definition indicates “device”, it refers to the ECG Belt Research System used 
in this study. 
Table 4: Adverse Event definitions 

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General 
Adverse Event (AE) 
(ISO 14155:2011, 3.2) 
Any untoward medical occurrence, unintended disease or injury, 
or untoward clinical signs (including abnormal laboratory findings) 
in subjects, users or other persons, whether or not related to the 
investigational medical device 
 
NOTE 1: This definition includes events related to the 
investigational medical device or the comparator. 
NOTE 2: This definition includes events related to the procedures 
involved. 
NOTE 3: For users or other persons, this definition is restricted to 
events related to investigational medical devices. 
 
Adverse Device Effect (ADE) 
(ISO 14155:2011, 3.1) 
 
 
 
 
Adverse event related to the use of an investigational medical 
device 
 
NOTE 1: This definition includes adverse events resulting from 
insufficient or inadequate instructions for use, deployment, 
implantation, installation, or operation, or any malfunction of the 
investigational medical device. 
NOTE 2: This definition includes any event resulting from an error 
use or from intentional misuse of the investigational medical 
device. 
Device Deficiency (DD) 
(ISO 14155:2011, 3.15) 
 
 
Inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety or performance.  
 
NOTE: Device deficiencies include malfunctions, use errors and 
inadequate labeling 
Relatedness 
System related 
 
 
An adverse event that results from the presence, application or 
performance (intended or otherwise) of the ECG Belt Research 
System 
Not Related 
Relationship to the device or procedures can be excluded when: 
 The event is not a known side effect of the product category 
the device belongs to or of similar devices and 
procedures; 
 The event has no temporal relationship with the use of the 
device or the procedures; 
 The serious event does not follow a known response pattern 
to the medical device (if the response pattern is 
previously known) and is biologically implausible; 
 The discontinuation of medical device application or the 
reduction of the level of activation/exposure – when 
clinically feasible – and reintroduction of its use (or 
increase of the level of activation/exposure) do not 
impact the serious event; 
 The event involves a body-site or an organ not expected to 
be affected by the device or procedure; 
 The serious event can be attributed to another cause (e.g., 
an underlying or concurrent illness/clinical condition, an 
effect of another device, drug, treatment, or other risk 
factors); 
 The event does not depend on a false result given by the 
device used for diagnosis (when applicable); 
 Harms to the subject are not clearly due to use error; 
 
In order to establish the non-relatedness, not all the criteria listed 
above might be met at the same time, depending on the type of 
device/procedures and the event. 

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Unlikely 
The relationship with the use of the device seems not relevant 
and/or the event can be reasonably explained by another cause, 
but additional information may be obtained. 
Possible 
The relationship with the use of the investigational device is weak 
but cannot be ruled out completely. Alternative causes are also 
possible (e.g. an underlying or concurrent illness/ clinical condition 
or/and an effect of another device, drug or treatment). Cases were 
relatedness cannot be assessed or no information has been 
obtained should also be classified as possible. 
Probable 
The relationship with the use of the investigational device seems 
relevant and/or the event cannot reasonably explained by another 
cause, but additional information may be obtained.  
Causal Relationship 
The event is associated with the device or study procedures 
beyond reasonable doubt when: 
 The event is a known side effect of the product category the 
device belongs to or of similar devices and procedures; 
 The event has a temporal relationship with device 
use/application or procedures; 
 The event involves a body-site or organ that the device or 
procedures are applied to or the device or procedures 
have an effect on; 
 The serious event follows a known response pattern to the 
medical device (if the response pattern is previously 
known); 
 The discontinuation of medical device application (or 
reduction of the level of activation/exposure) and 
reintroduction of its use (or increase of the level of 
activation/exposure) impact on the serious event (when 
clinically feasible); 
 Other possible causes (e.g., an underlying or concurrent 
illness/clinical condition or/and an effect of another 
device, drug, or treatment) have been adequately ruled 
out; 
 Harm to the subject is due to error in use; 
 The event depends on a false result given by the device 
used for diagnosis (when applicable); 
 In order to establish the relatedness, not all the criteria listed 
above might be met at the same time, depending on the 
type of device/procedures and the serious event. 
Seriousness 
Serious Adverse Event (SAE) 
(ISO 14155:2011, 3.37) 
Adverse event that 
a) led to death, 
b) led to serious deterioration in the health of the subject, that 
either resulted in 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, 
or 
3) in-patient or prolonged hospitalization, or 
4) medical or surgical intervention to prevent life-threatening 
illness or injury or permanent impairment to a body structure or a 
body function, 
c) led to foetal distress, foetal death or a congenital abnormality or 
birth defect 
NOTE 1: Planned hospitalization for a pre-existing condition, or a 
procedure required by the CIP, without serious deterioration in 
health, is not considered a serious adverse event. 
 
 

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Serious Adverse Device Effect (SADE) 
(ISO 14155:2011, 3.36) 
 
 
Adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event. 
 
Unanticipated Adverse Device Effect 
(UADE) 
(21 CFR 812) 
 
 
 
Any serious adverse effect on health or safety or any life-
threatening problem or death caused by, or associated with, a 
device, if that effect, problem, or death, was not previously 
identified in a nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan 
or application), or any other unanticipated serious problem 
associated with a device that relates to the rights, safety, or 
welfare of subjects. (21 CFR 812.3(s)) 
Unanticipated Serious Adverse Device 
Effect (USADE) 
(ISO 14155:2011, 3.42) 
 
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 
NOTE 1: Anticipated serious adverse device effect (ASADE) is an 
effect which by its nature, incidence, severity or outcome has 
been identified in the risk analysis report. 
 
 
b. Adverse Event and Device Deficiency Assessment 
i. Adverse Events 
All ECG Belt Research System related and all Serious Adverse Events will be collected 
throughout the study duration, starting at the time of signing the ICF.  
Reporting of these events to Medtronic will occur on an Adverse Event (AE) Form, 
including a description of AE, date of onset of AE, date of awareness of site, treatment, 
resolution, assessment of both the seriousness and the relatedness.  Each AE must be 
recorded on a separate AE Form. Subject deaths are also required to be reported. Refer 
to Section 10.e. for Subject Death collection and reporting requirements. In addition, AEs 
impacting users or other persons, Non-subject Adverse Events, (reportable per ISO 
14155) will be collected. 
Documented pre-existing conditions are not considered AEs unless the nature or 
severity of the condition has worsened.  
For AEs that require immediate reporting, initial reporting may be done by phone, fax, 
email (see Sponsor Contact Information) or on the CRF completing as much information 
as possible. The AE CRF must be completed as soon as possible.  
ii. Device Deficiencies 
Device deficiency information for the ECG Belt Research System will be collected 
throughout the study and reported to Medtronic. Note that device deficiencies that result 
in an adverse device effect (ADE) to the subject should be captured as an Adverse 
Event only. 
Device deficiencies that did not lead to an AE but could have led to a Serious Adverse 
Device Effect (SADE) (i.e., if suitable action had not been taken, if intervention had not 
been made, or if the circumstances had been less fortunate) require immediate reporting 
(see Table 6). 
iii. Processing Updates and Resolution 
For any changes in status of a previously reported adverse event (i.e. change in actions 
taken, change in outcome, change in relatedness), an update to the original AE must be 

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completed. All reported AEs must be followed until the AE has been resolved, is 
unresolved with no further actions planned, the subject dies or exits the study, or until 
study closure, whichever occurs first.  
In the event that a subject is exited from the study prior to study closure, all efforts 
should be made to continue following the subject until all unresolved system related 
AEs, as classified by the investigator, are resolved or they are unresolved with no further 
actions planned.  
At the time of study exit, all collected AEs with an outcome of “Unresolved, further 
actions or treatment planned” must be reviewed and an update to the original AE must 
be reported. At a minimum, if there are no changes to the description, relatedness, test 
and procedures or actions taken, the outcome must be updated to reflect “Unresolved at 
time of study closure.” 
 
c. Adverse Events and Deficiency Classification 
All reported AEs and device deficiencies will be reviewed by a Medtronic representative. 
AEs will be classified according to the definitions provided.  
Upon receipt of AEs at Medtronic, a Medtronic representative will review the AE/device 
deficiency for completeness and accuracy and when necessary will request clarification 
and/or additional information from the Investigator. Medtronic will utilize MedDRA, the 
Medical Dictionary for Regulatory Activities, to assign a MedDRA term for each adverse 
event based on the information provided by the investigator.  
Regulatory reporting of AEs and device deficiencies that could have led to an SADE will 
be completed according to local regulatory requirements. Refer to Table 9 for a list of 
required investigator and Medtronic reporting requirements and timeframes. It is the 
responsibility of the investigator to abide by any additional AE reporting requirements 
stipulated by the Ethics Committee responsible for oversight of the study. 
For a Foreseeable Adverse Event List (FAL), please refer to the Investigator’s Brochure. 
This is a list of AEs related to the ECG Belt Research System or application procedure 
that have been observed in previous studies and may be experienced by subjects. This 
list may help to assess if an AE is unexpected in nature. For emergency contact 
regarding a UADE, SAE and/or SADE, contact a clinical study representative 
immediately (refer to the study contact list provided in the center’s study documents 
binder/investigator site file or refer to the contact information provided on the title page). 
Adverse Events and Deaths will be classified according to the standard definitions as 
outlined below: 
 
Table 5:  Adverse Event classification responsibilities 

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What is classified?  Who classifies? Classification Parameters 
Relatedness 
Investigator 
ECG Belt Research System (Belt, amplifier, software, 
tablet, application procedure), heart failure related 
hospitalizations  
Sponsor 
ECG Belt Research System (Belt, amplifier, software, 
tablet, application procedure), heart failure related 
hospitalizations 
Severity 
Investigator 
SAE 
Sponsor 
SAE, UADE/USADE, Device Deficiency with SADE 
potential 
Diagnosis 
Investigator 
Based on presenting signs and symptoms and other 
supporting data 
Sponsor 
MedDRA term assigned based on the data provided by 
Investigator 
Death Classification Investigator 
Sudden Cardiac, Non-sudden Cardiac, Non-Cardiac, 
Unknown 
 
Medtronic will review and trend AEs and if necessary, take any actions considered 
appropriate to protect subject safety. Medtronic has documented procedures for 
suspending a study in the event the safety or the welfare of the subjects is endangered.  
 
d. Adverse Event and Device Deficiency Reporting Requirements 
Regulatory reporting of AEs/device deficiencies will be completed according to local 
regulatory requirements. Refer to Table 6 for a list of required investigator reporting 
requirements and timeframes, and of required Medtronic reporting requirements and 
timeframes. 
 
The investigator is required to report all SAE’s to Medtronic immediately, and to the 
Ethics Committee per local requirements. Medtronic is also required to report these 
events to the local regulatory authority based on their requirements. It is the 
responsibility of the investigator to abide by any additional AE/device deficiency 
reporting requirements stipulated by the Ethics Committee responsible for oversight of 
the study. 
 
For AEs/device deficiencies that require immediate reporting, initial reporting may be 
done by contacting the study sponsor per the sponsor contact information provided in 
this document.  
 
Regulatory reporting of AEs/device deficiencies that could have led to an SADE will be 
completed according to local regulatory requirements. Refer to Table 6: Reporting 
Requirements for a list of required investigator and Medtronic reporting requirements 
and timeframes. Each geography has the responsibility to follow current local reporting 
requirements. 
 
 
 
 
Table 6: Adverse Event reporting requirements 

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Serious Adverse Events (SAEs) 
Investigator submit to: 
Medtronic 
Europe: Immediately after the investigator first learns of the event or new information in 
relation with an already reported event. (ISO14155 and local law)  
All other geographies: Submit in a timely manner after the investigator first learns of the 
event. 
 
Ethics 
Committee,  
Europe: Submit to Ethics Board per local reporting requirement 
All other geographies: Submit per local EC requirement. 
 
Regulatory 
authorities 
Europe: Submit to regulatory authorities per local reporting requirement 
All other geographies: Submit per local reporting requirement. 
 
Sponsor submit to: 
Regulatory 
authorities 
Europe: Submit to Competent Authority per local reporting requirement. 
All other geographies: Submit per local reporting requirement. 
 
Ethics 
Committee 
Europe: Submit to Ethics Board per local reporting requirement. 
All other geographies: Submit per local reporting requirement. 
 
Serious Adverse Device Effects (SADEs) 
 
Note: in this study ‘device’ refers to the ECG Belt Research System 
Investigator submit to: 
Medtronic 
Canada: Investigators are required, per the TPD Investigator Agreement, to report any 
incident that is related to a failure of the device or deterioration in its effectiveness, or any 
inadequacy in its labeling or directions for use leading to death or serious deterioration in a 
subject’s health within 72 hours after the occurrence. (Canada Medical Device Regulations, 
SOR/98-282; 77, 59) 
Europe: Immediately after the investigator first learns of the event or of new information in 
relation with an already reported event. ((ISO 14155 and local law). 
All other geographies: Immediately after the investigator first learns of the event or of new 
information in relation with an already reported event. 
Ethics 
Committee 
Europe: Submit to Ethics Board per local reporting requirement 
All other geographies: Submit per local EC requirement. 
 
Regulatory 
authorities 
Canada: Investigators are required, per the TPD Investigator Agreement, to report any 
incident that is related to a failure of the device or deterioration in its effectiveness, or any 
inadequacy in its labeling or directions for use leading to death or serious deterioration in a 
subject’s health within 72 hours after the occurrence. (Canada Medical Device Regulations, 
SOR/98-282; 77, 59) 
All other geographies: Immediately after the investigator first learns of the event or of new 
information in relation with an already reported event. 
 
Sponsor submit to: 

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Regulatory 
authorities 
Canada: Preliminary and final reporting to the Canadian Ministry of Health of events occurring 
inside (always) or outside Canada (in case of corrective actions) that is related to a failure of 
the device or a deterioration in its effectiveness, or any inadequacy in its labeling or its 
directions for use and has led to the death or a serious deterioration in the state of health of a 
patient, user or other person or could do so were it to recur. Report a) within 10 days after 
awareness, if incident has led to death or a serious deterioration in the state of health of a 
patient, user or other person b) within 30 days, if incident has not led to led to death or a 
serious deterioration in the state of health of a patient, user or other person, but could do so 
were it to recur c) as soon as possible, if incident occurred outside of Canada and is related to 
a corrective action. (Canada Medical Device Regulations, SOR/98-282; Mandatory Problem 
Reporting 59(1) , 59(2), 60 (1)) 
All other geographies: Submit per local reporting requirement. 
 
Ethics 
Committee 
Europe: Submit to Ethics Board per local reporting requirement. 
All other geographies: Submit per local reporting requirement. 
 
Unanticipated Adverse Device Effects (UADEs) and 
Unanticipated Serious Adverse Device Effects (USADEs) 
 
Note: in this study ‘device’ refers to the ECG Belt Research System 
Investigator submit to: 
Medtronic 
Canada: Investigators are required, per the Therapeutic Products Directorate Investigator 
Agreement, to report any incident that is related to a failure of the device or deterioration in its 
effectiveness, or any inadequacy in its labeling or directions for use leading to death or serious 
deterioration in a subject’s health within 72 hours after the occurrence. (Canada Medical 
Device Regulations, SOR/98-282; 77, 59) 
US: Submit as soon as possible, but no later than within 10 working days after the investigator 
first receives notice of the effect. (21 CFR 812.150(a)(1)) 
Europe: Immediately after the investigator first learns of the event or of new information in 
relation with an already reported event (ISO 14155 and local law). 
 
 
Ethics 
Committee 
US: Submit as soon as possible, but no later than within 10 working days after the investigator 
first receives notice of the effect. (21 CFR 812.150(a)(1)) 
All other geographies: Submit per local reporting requirement. 
 
 
Regulatory 
authorities 
Canada: Investigators are required, per the TPD Investigator Agreement, to report any 
incident that is related to a failure of the device or deterioration in its effectiveness, or any 
inadequacy in its labeling or directions for use leading to death or serious deterioration in a 
subject’s health within 72 hours after the occurrence. (Canada Medical Device Regulations, 
SOR/98-282; 77, 59) 
Europe: Submit per local reporting requirement. 
Sponsor submit to: 
Investigator 
All geographies: Notification as soon as possible, but not later than 10 working days after the 
sponsor first learns of the effect. (21 CFR 812.150(b)(1)) 
 

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Regulatory 
authorities 
Canada: Preliminary and final reporting to the Canadian Ministry of Health of events occurring 
inside (always) or outside Canada (in case of corrective actions) that is related to a failure of 
the device or a deterioration in its effectiveness, or any inadequacy in its labeling or its 
directions for use and has led to the death or a serious deterioration in the state of health of a 
patient, user or other person or could do so were it to recur. Report a) within 10 days after 
awareness, if incident has led to death or a serious deterioration in the state of health of a 
patient, user or other person b) within 30 days, if incident has not led to led to death or a 
serious deterioration in the state of health of a patient, user or other person, but could do so 
were it to recur c) as soon as possible, if incident occurred outside of Canada and is related to 
a corrective action. (Canada Medical Device Regulations, SOR/98-282; Mandatory Problem 
Reporting 59(1) , 59(2), 60 (1)) 
US: Notification as soon as possible to FDA, but not later than 10 working days after the 
sponsor first receives notice of the effect. (21 CFR 812.150(b)(1)) 
Europe: Submit per local reporting requirement. 
Ethics 
Committee 
US: Notification as soon as possible, but not later than 10 working days after the sponsor first 
learns of the effect. (21 CFR 812.150(b)(1)) 
All geographies: Submit USADE to IRB/MEC per local reporting requirement. 
 
Device Deficiencies with SADE potential 
 
Note: in this study ‘device’ refers to the ECG Belt Research System 
Investigator submit to: 
Medtronic 
 
Canada: Investigators are required, per the TPD Investigator Agreement, to report any 
incident that is related to a failure of the device or deterioration in its effectiveness, or any 
inadequacy in its labeling or directions for use leading to death or serious deterioration in a 
subject’s health within 72 hours after the occurrence. (Medical Devices Regulations, SOR/98-
282; 77, 59) 
Europe: Immediately after the investigator first learns of the deficiency or of new information in 
relation with an already reported deficiency. 
All other geographies: Submit or report as required per local reporting requirements 
 
Ethics 
Committee 
All geographies: Submit per local EC requirement 
 
Regulatory 
authorities 
All geographies: Submit per local reporting requirement. 
Sponsor submit to: 
Regulatory 
authorities 
Canada: Preliminary and final reporting to the Canadian Ministry of Health of events occurring 
inside (always) or outside Canada (in case of corrective actions) that is related to a failure of 
the device or a deterioration in its effectiveness, or any inadequacy in its labeling or its 
directions for use and has led to the death or a serious deterioration in the state of health of a 
patient, user or other person or could do so were it to recur. Report a) within 10 days after 
awareness, if incident has led to death or a serious deterioration in the state of health of a 
patient, user or other person b) within 30 days, if incident has not led to death or a serious 
deterioration in the state of health of a patient, user or other person, but could do so were it to 
recur c) as soon as possible, if incident occurred outside of Canada and is related to a 
corrective action. (Canada Medical Device Regulations, SOR/98-282; Mandatory Problem 
Reporting 59(1) , 59(2), 60 (1)) 
All geographies: Submit per local reporting requirement 
 
Ethics 
Committee 
All geographies: Submit per local EC requirement. 
 

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All other Device Deficiencies 
 
Note: in this study ‘device’ refers to the ECG Belt Research System 
Investigator submit to: 
Medtronic 
All geographies: Submit in a timely manner after the investigator first learns of the deficiency. 
 
Regulatory 
Authorities 
All geographies: Submit or report as required per local reporting requirement. 
 
Ethics 
Committee 
All geographies: Submit per local EC requirement. 
 
 
e. Subject Death 
i. 
Death data collection 
When a subject dies during the study, the death must be reported using an Adverse 
Event CRF with an outcome of death as soon as possible after the investigator first 
learns of the death. There should be only one AE CRF with an outcome of death.  
A copy of the death certificate, if available and allowed by state/local law, should be sent 
to the Medtronic clinical study team. When a death occurs in a hospital, a copy of the 
death summary report and all relevant hospital records should be sent to the Medtronic 
clinical study team, if available. If an autopsy is conducted, the autopsy report should 
also be sent to the Medtronic clinical study team if available and allowed by state/local 
law. When the death occurs at a remote site, it is the investigative center’s responsibility 
to attempt retrieval of information about the death. Additionally, device disposition 
information should be updated. In summary, the following data will be collected: 
• 
Date of death 
• 
Detailed description of death 
• 
Cause of death  
• 
Device interrogation (if available) 
• 
Device disposition information 
• 
Death summary/hospital records (if available and allowed by state/local 
law) 
• 
Autopsy report (if available and allowed by state/local law) 
• 
Death certificate (if available and/or allowed by state/local law) 
ii. 
Death classification and reporting 
Sufficient information will be required in order to properly classify the subject’s death. 
The Investigator shall classify each subject death per the following definitions: 
Cardiac Death: A death directly related to the electrical or mechanical 
dysfunction of the heart. 
Sudden Cardiac Death (SCD): Natural death due to cardiac causes, indicated by 
abrupt loss of consciousness within one hour of the onset of acute symptoms; 
preexisting heart disease may have been known to be present, but the time and 
mode of death are unexpected. If time of onset cannot be determined, SCD will 

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alternatively be defined as any unexpected cardiac death occurring out of the 
hospital or in the emergency room as dead on arrival. 
Non-sudden Cardiac Death: All cardiac deaths that are not classified as sudden 
deaths, including all cardiac deaths of hospitalized subjects on inotropic support. 
Non-cardiac Death: A death not classified as a cardiac death. 
Unknown Classification: Unknown death classification is intended for use only 
when there is insufficient or inadequate information to classify the death. 
 
Regulatory reporting of Subject Deaths will be completed according to local regulatory 
requirements. Refer to Table 6 for a list of required investigator and sponsor reporting 
requirements and timeframes. 
 
f.  Clinical event review 
Medtronic will review and trend AEs and if necessary, take any actions considered 
appropriate to protect subject safety. Medtronic has documented procedures for 
suspending a study in the event the safety or the welfare of the subjects is endangered. 
Since anticipated risks and AEs related to the ECG Belt Research System are minor, a 
Clinical Events Committee and Data Monitoring Committee are not planned. 
 
g. Product Complaint Reporting 
In geographies where devices are market-released, product complaint reporting is 
applicable. This includes when an AE is related to a market-released device during the 
study. The reporting of product complaints is not part of the clinical study and should be 
done in addition to the Adverse Event reporting requirements. Refer to local regulations 
for reporting requirements. 
Product Complaint: Any written, electronic or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, safety, effectiveness or 
performance of a medical device that has been placed on the market. 
It is the responsibility of the investigator to report all product complaint(s) associated with 
a medical device distributed by Medtronic, regardless whether they are related to 
intended use, misuse or abuse of the product. Reporting must be done immediately and 
via the regular channels for market-released products. 
Medtronic will notify the regulatory authorities (e.g. Competent Authority) as applicable 
for the following incidents immediately upon learning of them: 
• 
Any malfunction or deterioration in the characteristics and/or performance 
of the investigational device, as well as any inadequacy in the labeling or 
instructions for use which led or might have led to the death or serious 
deterioration in the state of health of a patient, user, or other person. 
• 
Any technical or medical reason resulting in withdrawal of a device from 
the market by the manufacturer. 
• 
An adverse event that led to death. 
• 
An adverse event that led to a serious deterioration in the state of heath 
that either resulted in: 

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o Life-threatening illness or injury 
o Permanent impairment of a body function or permanent damage 
to a body structure 
o A condition necessitating medical or surgical intervention to 
prevent permanent impairment of a body function or permanent 
damage to a body structure. 
• 
An adverse event that led to fetal distress, fetal death or any congenital 
abnormality or birth defects. 
11. 
RISK ANALYSIS 
Medtronic follows rigorous Risk Management procedures throughout the life of the 
research system, from the research and development phase through the study phase. 
The risk management process for the ECG Belt Research System is being performed in 
accordance with ISO 14971, and will ensure that the level of risk has been reduced as 
low as possible and is acceptable prior to starting the clinical study. A summary of the 
risk analysis and risk assessment is provided in the Investigator Brochure. Critical 
changes impacting the overall risk of the study will be documented through update of the 
Investigator Brochure and disclosed to subjects as needed.  
If changes are made to components of the ECG Belt Research System throughout the 
course of the study, Medtronic will ensure these changes do not impact the scientific 
soundness and safety of the study. The risk analysis and risk assessment summaries 
will be updated in the Investigator Brochure, and IRBs/MECs will be informed and 
approve these changes per local requirement before use in the study. 
For more details on the risk analysis of the ECG Belt Research System, refer to the ECG 
Belt Risk Management Report. The Risk Analysis in this report only addresses ECG Belt 
Research System risks. 
Use of the ECG Belt Research System introduces a small duration impact to the 
procedure which it is being added to. The set-up of the ECG Belt Research System is 
estimated to take approximately 10 minutes. At implant, this set-up time takes place 
outside of the sterile portion of the CRT procedure.  
For ECG Belt arm subjects, the contribution to the implant procedure is estimated to be 
approximately 40 minutes when two pacing locations are evaluated. For follow-up 
usage, the incorporation of the ECG Belt Research System is estimated to take 
approximately 40 minutes for both ECG Belt and control arm subjects. 
Note that eligible patients are already planned for a standard CRT system implant. 
Inherent CRT system and implant related risks and risks related to standard X-ray 
procedures as part of CRT implantation are therefore not in scope as study risks. These 
include, but are not limited to the following: valve damage; puncture of the heart muscle, 
vein, artery or lung; infection; a blood or air embolism in the heart, lung, arteries or veins; 
bleeding; hematoma; seroma; hemothorax; pneumothorax; swelling/bruising; stimulating 
muscles or nerves outside the heart; induction of an irregular heartbeat or arrhythmia; 
damage to a central vein or epicardial vein including dissection and perforation; 
arteriovenous fistula; pseudo-aneurysm; or localized pain where the incision is made to 
insert the catheters and CRT device and leads and radiation burden, skin reaction and 
slight increase in cancer risk. 
 

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Possible risks specific for participating in this study include the following (other 
unforeseen risks may also be possible): 
• 
ECG Belt Research System related risks: 
o At Implant (ECG Belt arm only): The non-invasive ECG Belt Research 
System is investigational but has been qualified for human use and tested 
for safety similar to standard ECG recording systems. There may be 
allergenic reaction, skin redness or irritation or discomfort from the 
additional ECG Belt electrodes, minor pain or discomfort while attaching 
and detaching multiple electrodes to the skin, and discomfort due to lying 
on the ECG Belt. Since a larger surface is covered by the ECG Belt, the 
area of irritation skin redness or irritation may be larger than with standard 
ECG electrode systems. Use of the ECG Belt Research System during 
the LV lead implant procedure may add to the length of sterile procedure 
time. ECG Belt Research System testing at the first location is estimated 
to take approximately 10 minutes. If the implanter moves the lead to a 
second location based on the ECG Belt Research System metrics, this 
could add approximately 20 minutes to move the lead plus 10 minutes for 
ECG Belt Research System testing at the second location. 
o At follow-ups (all subjects): The non-invasive ECG Belt Research 
System is investigational but has been qualified for human use and tested 
for safety similar to standard ECG recording systems. There may be skin 
redness or irritation from the additional ECG Belt electrodes, minor pain 
or discomfort while attaching and detaching multiple electrodes to the 
skin, and discomfort due to lying on the ECG Belt. Since a larger surface 
is covered by the ECG Belt, the area of skin redness or irritation may be 
larger than with standard ECG electrode systems. The use of the ECG 
Belt Research System may add approximately 40 minutes of time to 
follow-up visits for testing various CRT parameters, plus 10 minutes for 
application of the ECG Belt and System setup.  
o During the study (for ECG Belt arm and control arm A): There is a 
potential risk that errors, omissions or inaccuracies of ECG Belt Research 
System may provide feedback that results in suboptimal LV location 
and/or suboptimal programming and reduced CRT response. 
There may be additional risks related to use of the ECG Belt Research System 
that are unknown at this time. 
 
Other risks related to participation in the study: 
• 
All study subjects will have to undergo a higher number of echocardiogram 
procedures than in normal practice (e.g. echo at baseline, 6 month and 9 
month follow-up). The placement of the ultrasound probe may cause 
discomfort, but the echocardiogram imaging procedure itself does not pose 
any additional risk to the subject. 
 

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a. Risk Minimization 
The potential risks associated with the ECG Belt Research System and other 
potential risks of study participation were identified and risk control measures were 
defined. Any potential risks associated with this study are further minimized by 
selecting qualified investigators and training study personnel on the Clinical 
Investigation Plan. In the event that subjects do not respond to CRT during the 
study, the required use of quadripolar LV leads will provide investigators more 
options to improve CRT response after the study has ended.  
In addition, investigators will be actively involved in the implantation and follow-up 
of the subjects implanted with the CRT systems.  
Risks will be minimized by careful assessment of each subject prior to, during, and 
after implant of the indicated CRT implant. Investigators will continuously monitor, 
assess and document risks. 
Medtronic has further minimized the possibility of risks by providing guidelines for 
subject selection and evaluation, and will provide adequate instructions and 
labeling.  
Table 7:  Potential risks and risk minimization strategy 
Potential risk  
Risk Control Strategy 
Bioincompatibility (including toxicity, 
sensitivity and allergenic reactions): 
Characteristics of the ECG Belt materials 
(electrodes, and surface electrode gel) may 
introduce an undesirable physiological 
response when a patient/ user is exposed to 
it. 
• 
The ECG Belt complies with the Biological 
evaluation of medical device standard, EN ISO 
10993. 
Misleading/ Misinformation causing 
insufficient/ inappropriate medical 
intervention: 
Errors, omissions or inaccuracies of ECG 
Belt Research System may provide feedback 
that results in suboptimal LV location and/or 
suboptimal programming and reduced CRT 
response 
• 
Study population are those patients that are 
known to have lower likelihood of response to 
typical LV lead placement and device 
programming. 
 
• 
Implanters are expected to follow the EHRA/HRS 
guidelines for CRT implant and will be instructed 
to stay within the recommended locations for LV 
lead implantation and optimize pacing 
vector/timing parameters (during implant and 
follow-up) in line with EHRA/HRS expert 
consensus19.  
 
• 
Efficacy data from pre-clinical ECG Belt system 
studies support the use of ECG Belt system LV 
lead placement during this study5. 
 
• 
Functional testing will be performed to ensure 
product integrity and safe performance when 
exposed to surrounding environment. 
 
• 
The User Manual will include instructions and 
precautions to be considered regarding system 
operation. 
 

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Potential risk  
Risk Control Strategy 
Precursor to infection: 
The use of the ECG Belt Research System 
or procedural designs of the research study 
may increase the risk of patient infection, due 
to lengthened CRT procedure duration. 
• 
The ECG Belt Research System workflow steps 
are designed to have a minimal duration impact 
to the baseline sterile portion of the CRT implant 
procedure (approximately 40 minutes if two lead 
locations are tested).  
 
Precursor to acute tissue trauma: 
The use of electrical equipment in contact 
with the patient introduces the potential for 
harmful currents to be applied.  
• 
Basic/electrical safety testing will be performed to 
ensure product safety as a human contacting 
device. 
 
There is a negligible impact to the implantable device’s longevity with the ECG Belt 
study. The interrogations included at implant and follow-up visits are part of 
standard of care for CRT patients and they have a negligible impact on the 
device’s longevity.  
 
b. Potential Benefits 
The ECG Belt Research System may offer benefit. Medtronic data on file has 
demonstrated that ECG Belt system metrics have superior sensitivity and 
specificity for finding the best LV pacing location (compared to QLV or QRS 
narrowing). While these data are based on retrospective analysis, the potential 
benefit to subjects is that CRT response rate and magnitude of CRT response may 
be improved through use of the ECG Belt Research System.  
Additionally, information collected from this study may assist in the design of new 
product(s)/therapy(ies) and/or instructions for use. 
 
c. Risk-benefit rationale 
The study population is known to have a lower likelihood of response to CRT with 
typical LV lead placement and device programming without an option for evaluating 
if pacing resynchronizes the patient. 
The use of ECG Belt Research System during implant would help the implanter 
with this information and may help confirming a suitable implant site and choosing 
the most optimal pacing settings which resynchronize the heart, in addition to 
satisfying other criteria (lead stability, clinically acceptable thresholds, no phrenic 
stimulation). The ECG Belt application and evaluation may add time to the implant 
procedure of approximately 40 minutes when two lead locations are tested, but 
may result in better response to CRT therapy.  
The use of ECG Belt Research System for management during follow-up would 
help the physician with this information and may help choose the most optimal 
pacing settings which resynchronize the heart, in addition to satisfying other criteria 
(clinically acceptable thresholds, no phrenic stimulation). The ECG Belt Research 
System setup and evaluation may add approximately 40 minutes to the follow up 
procedure but may result in better response to CRT therapy. 
The ECG Belt Study risks have been analyzed, evaluated and controls put in place 
to address all identified risks. The individual risks have been reduced as low as 

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possible, the risks are outweighed by the potential benefits, and the overall residual 
risk evaluated and disclosed via the ICF.  
 
 
12. 
PLANNED STUDY CLOSURE, EARLY 
TERMINATION OF STUDY OR STUDY SUSPENSION 
a. Planned study closure 
Study Closure is a process initiated by distribution of a study closure letter. Study 
closure is defined as closure of a clinical study that occurs when Medtronic and/or 
regulatory requirements have been satisfied per the CIP and/or by a decision by 
Medtronic or regulatory authority, whichever occurs first. The study closure 
process is complete upon distribution of the Final Report or after final payments, 
whichever occurs last. Ongoing Ethics Committee oversight is required until the 
overall study closure process is complete. Refer to Section 7q for additional 
information regarding study exit procedures. 
 
b. Early termination or suspension 
Early Termination is the closure of a clinical study or single site that occurs prior to 
meeting defined endpoints. Suspension is a temporary postponement of study 
activities related to enrollment and distribution of the product. This is possible for 
the whole study or a single center. 
i. 
Study-wide termination or suspension 
Possible reasons for considering study suspension or termination include but 
are not limited to: 
• 
Adverse events associated with the system or product under investigation 
which might endanger the safety or welfare of the subject 
• 
Observed/suspected performance different from the product’s design intent 
• 
Decision by Medtronic or regulatory body (where the study is operating 
under regulatory body authority)  
• 
Technical issues during the manufacturing process 
• 
When the risks are found to outweigh the potential benefits or when there 
is conclusive proof of definitive outcomes, investigators must assess 
whether to continue, modify or immediately stop the study. 
ii. 
Investigator/center termination or suspension 
Possible reasons for clinical investigator or center termination or suspension 
include but are not limited to: 
• 
Failure to obtain initial Ethics Committee approval or annual renewal of the 
study 

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• 
Persistent non-compliance to the clinical investigation (e.g. failure to 
adhere to inclusion/exclusion criteria, failure to follow subjects per 
scheduled follow-ups)  
• 
Lack of enrollment 
• 
Noncompliance to regulations and the terms of the Clinical Trial Agreement 
(e.g. failure to submit data in a timely manner, failure to follow-up on data 
queries and monitoring findings in a timely manner, etc.)  
• 
Ethics Committee suspension of the center 
• 
Fraud or fraudulent misconduct is discovered (as defined by local law and 
regulations)  
• 
Investigator request (e.g. no longer able to support the study)  
 
c. Procedures for termination or suspension 
i. 
Medtronic-initiated and regulatory authority-initiated 
• 
Medtronic will promptly inform the clinical investigators of the termination or 
suspension and the reasons and inform the regulatory authority(ies) where 
required 
• 
In the case of study termination or suspension for reasons other than a 
temporary MEC/IRB/Head of Medical Institution approval lapse, the 
investigator will promptly inform the MEC/IRB/Head of Medical Institution  
• 
In the case of study termination, the investigator must inform the subjects 
and may inform the personal physician of the subjects to ensure 
appropriate care and follow-up is provided 
• 
In the case of a study suspension, subject enrollment must stop until the 
suspension is lifted by Medtronic 
• 
In the case of a study suspension, enrolled subjects should continue to be 
followed out of consideration of their safety, rights and welfare 
ii. 
Investigator-initiated 
• 
The investigator will inform Medtronic and provide a detailed written 
explanation of the termination or suspension 
• 
The investigator will promptly inform the institution (where required per 
regulatory requirements)  
• 
The investigator will promptly inform the MEC/IRB/Head of Medical 
Institution 
• 
The investigator will promptly inform the subjects and/or the personal 
physician of the subjects to ensure appropriate care and follow-up is 
provided 
• 
In the case of a study suspension, subjects enrolled should continue to be 
followed out of consideration of their safety, rights and welfare 
iii. 
Ethics committee-initiated 
• 
The investigator will inform Medtronic and provide a detailed written 
explanation of the termination or suspension within 5 business days 

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• 
Subject enrollment must stop until the suspension is lifted 
• 
Subjects already enrolled should continue to be followed in accordance 
with MEC/IRB/Head of Medical Institution policy or its determination that an 
overriding safety concern or ethical issue is involved 
• 
The investigator will inform his/her institution (where required per local 
requirements)  
• 
The investigator will promptly inform the subjects and/or the personal 
physician of the subjects, with the rationale for the study termination or 
suspension 
 
 
13. 
STATISTICAL METHODS AND DATA ANALYSIS 
a. Sample size determination 
The sample size of the study will be 400 randomized subjects. It will require 
approximately 500 enrolled to acquire 400 randomized, but enrollment will end once 400 
are randomized. It is allowable to go over 400 randomized if the final randomizations 
occur within a week. As this is a research study, the sample size was based on budget, 
however power calculations can be found in the primary objective below.  
 
b. General considerations  
Data analysis will be performed by Medtronic-employed statisticians or designees. Data 
analysis will occur after 6-month follow-up data is collected and once final study data is 
collected. A modified intention-to-treat analysis will be performed and will serve as the 
primary analysis for all objectives in this study. The modified intention-to-treat cohort will 
include all CRT-implanted randomized subjects in the group to which they were 
randomized. Since this is a research study, there are no sample size requirements for 
these data analyses. 
All tests of treatment effects will be conducted at a two-sided alpha level of 0.05 unless 
otherwise stated. 
The Statistical Analysis Plan (SAP) will be developed prior to data analysis and will 
include a comprehensive description of the statistical methods and reports to be 
included in the final study report. Any change to the data analysis methods described in 
the CIP will require an amendment only if it changes a principal feature of the CIP. Any 
other change to the data analysis methods described in the CIP, and the justification for 
making the change, will be described in the clinical study report.  
The primary objective will be analyzed once the final 6-month follow-up is collected. 
Ancillary objectives may or may not be reported on at that time. The analysis of all 
objectives will appear in the study’s final report. 
c. Primary Objective 
Demonstrate benefit of using the ECG Belt Research System on reducing LVESV from 
baseline to 6 months post-implant compared to standard CRT. 

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i. 
Hypothesis 
H0: ∆ LVESVECG Belt = ∆ LVESVcontrol 
HA: ∆ LVESVECG Belt ≠ ∆ LVESVcontrol 
 
Where ∆ LVESV is the relative (%) change in LVESV from baseline to 6 months post-
implant calculated as 100 x (6-month LVESV – baseline LVESV) / baseline LVESV. 
 
ii. 
Performance Requirements 
The null hypothesis will be rejected if the p-value is less than 0.05. This is a research 
study, therefore if the ECG Belt arm has a better change in LVESV than the control arm, 
even if it is not statistically significant, the results could be interpreted as positive. 
iii. 
Rationale for Performance Criteria 
A reduction in LVESV has been shown to predict lower mortality rates in CRT patients22, 
and changes are seen soon after implant. An alpha level of 0.05 is a standard statistical 
criterion. 
iv. 
Analysis Methods 
The relative change in LVESV from baseline to 6 months will be calculated and 
compared using a two-sided, two-sample t-test. Subjects exiting, dying, or with missing 
LVESV at baseline or 6 months will not be included, and their data will not be imputed. 
 
If more than 10 randomized subjects fail to get implanted with an AdaptivCRT device 
and a Medtronic quadripolar LV lead, then a secondary analysis including only subjects 
successfully implanted with an AdaptivCRT device and a Medtronic quadripolar LV lead 
will be conducted. 
v. 
Determination of Subjects for Analysis  
All randomized subjects with paired LVESV data will be included. 
vi. 
Sample Size 
The sample size of approximately 200 subjects in the ECG Belt arm and 200 in the 
control arm was chosen based on budget considerations. Table 8 shows data from 
previous studies. The first row of the table shows that, among the patients meeting this 
study’s inclusion criteria, the mean relative change in LVESV at 6 months is -7.1 ± 27.5.    
 
So, it can be assumed that the control group without ECG Belt Research System 
management will decrease by a mean 7.1% over 6 months, with a standard deviation of 
27.5%. 
 
Table 8: LVESV Results from Previous CRT Studies’ CRT Patients 
Study 
n 
Mean ± S.D. Relative 
Change at 6 months in 
LVESV (%) 
All studies 
583 
-7.1 ± 27.5 

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Study 
n 
Mean ± S.D. Relative 
Change at 6 months in 
LVESV (%) 
MIRACLE 
125 
-9.2 ± 22.8 
MIRACLE ICD 
142 
-5.1 ± 25.1 
REVERSE 
124 
-8.2 ± 28.0 
Adaptive CRT control 
62 
-9.2 ± 32.3 
Adaptive CRT aCRT 
130 
-5.0 ± 31.3 
Note: To be included in the table, subjects must meet current indications for CRT (NYHA II with LVEF≤30% or NYHA 
III/IV), and have QRS≥130, LVEDD≥55, and (QRS<150 or Ischemic or non-LBBB) 
 
 
Figure 7 shows the power of the study under various values of improvement in LVESV 
due to the ECG Belt Research System under the following assumptions: 
• 
Alpha=0.05 
• 
Mean LVESV change in control population at 6 months is –7.1 ± 27.5% 
• 
ECG Belt Research System population subjects also have a standard deviation 
of 27.5% 
• 
180 subjects in the ECG Belt arm will have paired LVESV data, along with 180 
subjects in the control arm (10% attrition primarily due to deaths and unreadable 
echos at 6 months) 
 
The graph shows that the power of the study is 80% under the assumptions above if the 
ECG Belt Research System population reduces its mean LVESV by 15.3% (a 8.2% 
increase over the assumed control population mean relative change of 7.1%). As 
another example, if the ECG Belt Research System population has a mean reduction of 
14%, then the power of this objective is 66%. 
  
 

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Figure 7: Primary Objective #1 Power Curve 
 
 
d. Ancillary Objectives 
Though the following ancillary objectives have hypotheses to be tested, they are 
primarily intended to estimate various effects of the ECG Belt Research System. 
 
e. Ancillary Objective #1 
To estimate the benefit of using the ECG Belt Research System on LVEF compared to 
standard CRT. 
i. 
Endpoint Definition 
Absolute LVEF change from baseline to 6 months. 
ii. 
Analysis Methods 
The mean changes in LVEF will be compared between ECG Belt arm and control arm 
using a two-sided, two-sample t-test. 
iii. 
Determination of Subjects for Analysis  
All randomized subjects with paired LVEF data. 
 
f. Ancillary Objective #2 
To estimate the benefit of using the ECG Belt Research System on change in quality of 
life compared to standard CRT. 
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
-20
-18
-16
-14
-12
-10
-8
-6
-4
-2
0
Power
Assumed Mean Relative Change in LVESV (%) in the ECG Belt Population

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i. 
Endpoint Definition 
Quality of life will be measured using the Minnesota Living with Heart Failure 
Questionnaire. The endpoint is change from baseline to 6 months. Questionnaires with 
less than 11 questions answered will not be included. 
ii. 
Analysis Methods 
The mean changes in quality of life will be compared between ECG Belt arm and control 
arm using a two-sided, two-sample t-test. 
iii. 
 Determination of Subjects for Analysis  
All randomized subjects with paired Minnesota Living with Heart Failure Questionnaire 
data. 
 
g. Ancillary Objective #3 
To estimate the benefit of using the ECG Belt Research System on change in Six-Minute 
Walk Test distance compared to standard CRT. 
i. 
Endpoint Definition 
Six-Minute Walk Test distance will be measured at baseline and 6 months. The endpoint 
is change from baseline to 6 months. If the test at either time point was not done due to 
heart failure reasons, the distance will be considered to be 0. 
ii. 
Analysis Methods 
The mean changes in Six-Minute Walk Test distance will be compared between ECG 
Belt arm and control arm using a two-sided, two-sample t-test. 
iii. 
 Determination of Subjects for Analysis  
All randomized subjects with paired Six-Minute Walk Test distances, including those with 
a 0 distance on either or both the baseline and six-month visit due to heart failure. 
 
h. Ancillary Objective #4 
To estimate the benefit of using the ECG Belt Research System on the Clinical 
Composite Score compared to standard CRT.  
i. 
Endpoint Definition 
Clinical Composite Response23 will be evaluated at both 6 and 9 months post-implant. 
The description below is for 6 months, 9 months is analogous, but using 274 days 
instead of 182. 
 
A subject will be considered “worsened” if he/she experiences any of the following 
between randomization and the earlier of 182 days post-implant or his/her 6-month 
follow-up: 
• 
Death from any cause. 
• 
Hospitalization >24 hours due to or associated with worsening heart failure. 

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• 
Discontinues CRT due to or associated with worsening heart failure, 
treatment failure, or lack of/ insufficient therapeutic response.  
A subject will also be considered “worsened” if either of the following occurs: 
• 
A worsening in NYHA class at 6 months (as compared to baseline. 
• 
Moderate or marked worsening of the subject global assessment score at 6 
months. 
A subject will be considered “improved” if he/she is not “worsened” and one of 
the following is true: 
• 
An improvement in NYHA class at 6 months (as compared to baseline. 
• 
Moderate or marked improvement of the subject global assessment score at 
6 months. 
If a subject is neither “worsened” nor “improved”, and the subject has a 6-month 
follow-up, then he/she will be considered “unchanged”. 
ii. 
Analysis Methods 
Clinical Composite Response results will be reported at 6 months by randomization arm 
and compared using a chi-squared test. 
iii. 
Determination of Subjects for Analysis  
All randomized subjects who either worsen, or have a 6-month follow-up will be included. 
 
i. Ancillary Objective #5 
To characterize ECG Belt Research System related AEs. 
i. 
Endpoint Definition  
An AE will be considered related to the ECG Belt Research System if it is classified as 
system-related. 
ii. 
Analysis Methods 
The percentage of ECG Belt Research System uses with an AE related to them will be 
reported. The denominator for this calculation will be the number of times the ECG Belt 
Research System was used. For example, this is expected to be 4 times (during implant, 
post-implant, 6 months, and 9 months) for a subject randomized to the ECG Belt arm 
and completing the study. The numerator will be the number of ECG Belt Research 
System uses with at least one adverse event. A 95% confidence interval will be applied 
to the estimate as well using GEE methods with patient as a repeated variable. 
 
In addition, similar methods will be used to calculate the percentage of ECG Belt 
Research System uses with a serious adverse event related to the use of the ECG Belt 
Research System. 

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iii. 
Determination of Subjects for Analysis  
All ECG Belt Research System uses will be included. 
 
j. Ancillary Objective #6 
To assess the changes in LVESV from 6-9 months between subjects who have and 
have not used the ECG Belt Research System at 6 months. 
i. 
Endpoint Definition 
Relative LVESV change from 6 months to 9 months. 
ii. 
Analysis Methods 
The relative change in LVESV from 6 months to 9 months will be calculated and 
compared between control groups A and B using a two-sided, two-sample t-test.  
iii. 
Determination of Subjects for Analysis  
Only subjects in the control arm with paired LVESV data at 6 and 9 month follow up 
visits will be included. 
 
 
k. Ancillary Objective #7 
 
To assess the extent of ECG Belt Research System guided programming changes 
across study visits. 
i. 
Endpoint Definition 
Any change in programming due to use of the ECG Belt Research System.  This 
includes vector selection, Adaptive CRT programming mode, and A-V and V-V timing. 
ii. 
Analysis Methods 
The percentage of subjects whose programming is changed due to the ECG Belt 
Research System will be reported at each visit where the ECG Belt Research System is 
used.  Additionally, frequencies of types of changes (e.g., vectors, V-V timing) will be 
reported. 
iii. 
Determination of Data for Analysis  
All subject visits where the ECG Belt Research System was used post-implant will be 
included. 
 
 
 
14. 
DATA AND QUALITY MANAGEMENT 
Data will be collected using an electronic data management system for clinical studies. 
CRF data will be stored in a secure, password-protected database which will be backed 
up nightly. Data will need to be saved complete upon entry by the centers to make it 
available for review. Data review, database cleaning and issuing and resolving data 
queries will be done according to Medtronic internal Standard Operating Procedures. 

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Data will be reviewed using programmed and manual data checks. Data queries will be 
made available to centers for resolution. Sign-off of CRFs is required at the end of the 
study upon database closure. Study management reports may be generated to monitor 
data quality and study progress. At the end of the study, the data will be locked and will 
be retained indefinitely by Medtronic. 
All records and other information about subjects participating in this study will be treated 
as confidential. Data will be transferred and processed by Medtronic or a third party 
designated by Medtronic in a key coded form, unless it’s impossible to make it 
anonymous, for instance, where the subject’s name cannot be removed from the data 
carrier, such as, but not limited to, ECG and Echo images.  
Procedures in the CIP require source documentation. Source documentation will be 
maintained at the site. Source documents, which may include worksheets, patient 
medical records, programmer printouts, and interrogation files, must be created and 
maintained by the investigational site team.  
The investigator will clearly mark clinical records to indicate that the subject is enrolled in 
this study. Where copies of the original source document as well as print outs of original 
electronic source documents are retained, these shall be signed and dated by a member 
of the investigation site team with a statement that it is a true reproduction of the original 
source document. 
The data reported on the CRFs shall be derived from source documents and be 
consistent with these source documents, and any discrepancies shall be explained in 
writing. The CRF must be signed by the investigator. The CRF may be considered 
source for the following data collection elements: 
- 
LV Lead placement decisions 
- 
ECG Belt Research System measurements 
- 
CRT programming decisions 
- 
Device Tracking 
- 
Randomization assignment 
- 
The following Administrative information: 
o Date of baseline assessment 
o Date of most recent inclusion/exclusion criteria assessment 
o Date Medical History was assessed 
o Date study center became aware of the Adverse Event 
 
Hard copy data (if applicable) such as Echo (uploaded to a disk/USB) or 12-lead ECG 
(paper or uploaded to disk/USB) that is collected at Implant and/ or follow-up visits will 
be sent to Medtronic. Upon receipt, hard copy data will be maintained in a secure 
location and retrieved for analysis and reporting. 
The sponsor or a regulatory authority may audit or inspect the study center to evaluate 
the conduct of the study. The clinical investigator(s)/institution(s) shall allow study 
related monitoring, audits, Ethics Board review and regulatory inspection by providing 
direct access to source data/documents. 

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15. 
INSURANCE INFORMATION 
 
US and Canada: 
Medtronic maintains appropriate Clinical Trial liability insurance coverage as required 
under applicable laws and regulations and will comply with applicable local law and 
custom concerning specific insurance coverage. If required, a Clinical Trial insurance 
statement/certificate will be provided to the Ethics Committee. 
 
Europe: 
Medtronic Bakken Research B.V is a wholly owned subsidiary of Medtronic, which as the 
parent company of such entity maintains appropriate clinical trial liability insurance 
coverage as required under applicable laws and regulations and will comply with 
applicable local law and custom concerning specific insurance coverage. If required, a 
Clinical Trial insurance statement/certificate will be provided to the Ethics Committee. 
 
 
16. 
MONITORING 
It is the responsibility of Medtronic to ensure proper monitoring of this clinical study. 
Trained Medtronic personnel or delegates appointed by Medtronic may perform study 
monitoring at the study center in order to ensure that the study is conducted in 
accordance with the CIP, Medtronic Standard Operating Procedures, the Clinical Trial 
Agreement, and applicable regulatory and local requirements. Medtronic, or delegates, 
must therefore be allowed access to the subjects’ case histories (clinic and hospital 
records, and other source data/documentation) upon request as per the ICF, Research 
Authorization (where applicable) and Clinical Trial Agreement. The principal investigator 
should also be available during monitoring visits. 
 
a. Monitoring Visits 
Frequency of monitoring visits may be based upon subject enrollment, duration of the 
study, study compliance, number of AEs, number of deviations, findings from previous 
monitoring visits and any suspected inconsistency in data that requires investigation. 
Regulatory documents may be reviewed at each study center. Monitoring for the study, 
including site qualification visits, site initiation visits, interim monitoring visits, and 
closeout visits, and extent of source data verification will be done in accordance to the 
ECG Belt Monitoring Plan. 
Monitoring visits may be conducted periodically to assess site study progress, the 
investigator’s adherence to the CIP, regulatory compliance including but not limited to 
IRB/Ethics Committee approval and review of the study, maintenance of records and 
reports, and review of source documents against subject CRFs. Monitors review site 
regulatory and study compliance by identifying findings of non-compliance and 
communicating those findings along with recommendations for preventative/corrective 
actions to site personnel. Monitors may work with study personnel to determine 

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appropriate corrective action recommendations and to identify trends within the study or 
at a particular center.  
 
 
17. 
REQUIRED RECORDS AND REPORTS 
a. Investigator records 
The investigator is responsible for the preparation and retention of the records cited 
below. All of the below records, with the exception of case history records and case 
report forms, should be kept in the Investigator Site File (i.e., the study binder provided 
to the investigator) or Subject Study Binder. CRFs must be maintained and signed 
electronically within the electronic data capture system during the study. The following 
records are subject to inspection and must be retained for a period of two years (or 
longer as local law or hospital administration requires) after the date on which the 
investigation is terminated. 
• 
All correspondence between the IRB/MEC, sponsor, monitor, regulatory 
authority and the investigator that pertains to the investigation, including 
required reports.  
• 
Subject’s case history records, including:  
o Signed and dated informed consent form  
 
In U.S. and Canada, signed by subject.  
 
In Europe, signed and dated by subject and investigator.  
o Observations of AEs/adverse device effects/device deficiencies 
o Medical history 
o Implant and follow-up data  
o Documentation of the dates and rationale for any deviation from the 
protocol 
• 
List of investigation sites 
• 
All approved versions of the CIP, ICF, and Investigator’s Brochure (as 
applicable)  
• 
Signed and dated Clinical Trial Agreement 
• 
Current curriculum vitae of principal investigators (all geographies), and 
key members of investigation site team (Europe) 
• 
Financial Disclosures 
• 
Documentation of delegated tasks 
• 
IRB/MEC approval documentation. Written information that the investigator 
or other study staff, when member of the IRB/MEC, did not participate in 
the approval process. Approval documentation must include the Ethics 
Board composition, where required per local law.  
• 
Regulatory authority notification, correspondence and approval, where 
required per local law 
• 
Study training records for site staff 
• 
Insurance certificates (Europe)  

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• 
Device tracking log 
• 
Randomization list 
• 
Subject ID list 
• 
Any other records that FDA and local regulatory agencies require to be 
maintained 
• 
Final Study Report including the statistical analysis.  
 
b. Investigator reports 
The investigator is responsible for the preparation (review and signature) and 
submission to the sponsor of all CRFs, AEs and adverse device effects (reported per the 
country-specific collection requirements), device deficiencies, deaths, and any deviations 
from the CIP. If any action is taken by an IRB/MEC with respect to this clinical study, 
copies of all pertinent documentation must be forwarded to Medtronic in a timely 
manner. Reports are subject to inspection and to the retention requirements as 
described above for investigator records.  
Safety data investigator reporting requirements are listed in the Adverse Event section. 
The investigator shall prepare and submit in a complete, accurate and timely manner the 
reports listed in this section. 
Table 9: Investigator reports applicable for all geographies per Medtronic requirements 
Report  
Submit to 
Description/Constraints 
Withdrawal of 
IRB/MEC approval 
Sponsor and 
Relevant 
Authorities 
The investigator must report a withdrawal of approval by 
the reviewing IRB/MEC of the investigator’s part of the 
investigation within 5 working days. 
Study Deviations  
Sponsor and 
IRB/MEC 
Any deviation from the clinical investigational plan shall be 
recorded together with the explanation of the deviation. 
Notice of deviations from the CIP to protect the life or 
physical well-being of a subject in an emergency shall be 
given as soon as possible, but no later than 5 working days 
after the emergency occurred. Except in such emergency, 
prior approval is required for changes in the plan or 
deviations.  
Final Report 
IRBs/MECs and  
Relevant 
Authorities 
This report must be submitted within 3 months of study 
completion or termination. 
 
Table 10:  Additional Investigator reports applicable to the United States per FDA 
regulations 

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Report  
Submit to 
Description/Constraints 
Withdrawal of 
IRB/MEC approval 
(either suspension or 
termination) 
Sponsor 
The investigator must report a withdrawal of approval by 
the reviewing IRB/MEC of the investigator’s part of the 
investigation within 5 working days. (21 CFR 812.150(a)(2)) 
Progress report  
Sponsor and 
IRB/MEC 
The investigator must submit this report to the sponsor and 
IRB/MEC at regular intervals, but in no event less than 
yearly. (21 CFR 812.150 (a)(3)).  
Study deviations  
Sponsor and 
IRB/MEC 
Notice of deviations from the CIP to protect the life or 
physical wellbeing of a subject in an emergency shall be 
given as soon as possible, but no later than 5 working days 
after the emergency occurred. Except in such emergency, 
prior approval is required for changes in the plan or 
deviations. If the deviation may affect the scientific 
soundness of the plan or the rights, safety and welfare of 
the subjects, the deviation must be approved by Medtronic, 
the IRB/MEC, and the FDA/applicable regulatory 
authorities. If the deviation does not affect these issues 
then only Medtronic must approve it. (21 CFR 
812.150(a)(4)) 
Failure to obtain 
informed consent 
prior to 
investigational 
device use 
Sponsor and 
IRBs/MECs 
If an investigator uses a device without obtaining informed 
consent, the investigator shall report such use within 5 
working days after device use. (21 CFR 812.150(a)(5)) 
Final report 
Sponsor 
IRBs/MECs 
Relevant 
Authorities 
This report must be submitted within 3 months of study 
completion or termination of the investigation or the 
investigator’s part of the investigation. (21 CFR 
812.150(a)(6)) 
Other 
IRB/MEC and 
FDA 
An investigator shall, upon request by a reviewing 
IRB/MEC, FDA or any other regulatory agency, provide 
accurate, complete, and current information about any 
aspect of the investigation. (21 CFR 812.150(a)(7)) 
 
Table 11:  Additional Investigator reports applicable to Europe per ISO14155 
Report  
Submit to 
Description/Constraints 
Progress Report  
Sponsor and 
IRB/MEC 
Provide if required by local law or IRB/MEC.  
Study Deviations  
Sponsor and 
IRB/MEC 
Any deviation from the CIP shall be recorded together with 
an explanation for the deviation. Deviations shall be 
reported to the sponsor who is responsible for analyzing 
them and assessing their significance.  
Note: When relevant, ethics committees, competent 
authorities or the appropriate regulatory bodies should be 
informed. (ISO 14155:2011) 
Failure to obtain 
informed consent 
Sponsor and 
IRB/MEC 
Informed consent shall be obtained in writing and 
documented before a subject is enrolled into the clinical 
investigation. (ISO 14155:2011) 
 
c. Sponsor records 
Medtronic shall maintain the following accurate, complete, and current records: 
• 
All correspondence which pertains to the investigation 
• 
Investigational device traceability record 

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• 
Software traceability records 
• 
All approved informed consent templates, and other information 
provided to the subjects and advertisements, including translations 
• 
Copies of all IRB/MEC approval letters and relevant IRB/MEC 
correspondence and IRB/MEC voting list/roster/letter of assurance 
• 
Names of the institutions in which the clinical study will be conducted 
• 
Regulatory authorities correspondence, notification and approval as 
required by national legislation 
• 
Insurance certificates 
• 
Names/contact addresses of monitors 
• 
Statistical analyses and underlying supporting data 
• 
Final report of the clinical study 
• 
All approved versions of Clinical Investigation Plan, Investigator’s 
Brochure and study related reports, and revisions 
• 
Study training records for site personnel and Medtronic personnel 
involved in the study 
• 
Signed Investigator Trial Agreements, and current signed and dated 
curriculum vitae of principal investigator and key members of the 
investigation site team, signed delegated task list and dated case report 
forms submitted by investigator, including reports of AEs, ADEs and 
Device Deficiencies 
• 
Any other records that local regulatory agencies require to be 
maintained 
 
d. Sponsor reports 
Medtronic shall prepare and submit the following complete, accurate, and timely 
reports listed in the tables below (by geography). In addition to the reports listed 
below, Medtronic shall, upon request of reviewing IRB/MEC, regulatory agency or 
FDA, provide accurate, complete and current information about any aspect of the 
investigation. Safety data Medtronic reporting requirements are listed in the 
Adverse Event section. 
 
Table 12: Sponsor reports for Canada 
Report  
Submit to 
Description/Constraints 
Premature 
termination or 
suspension of the 
clinical investigation 
Investigators, 
IRB/MEC, 
Relevant 
authorities, and  
Head of the 
Institution 
Provide prompt notification of termination or suspension 
and reason(s). (ISO 14155:2011) 

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Submit to 
Description/Constraints 
Recall and device 
disposition 
Investigators, 
Head of 
Institution, 
IRB/MEC, 
relevant 
authorities, and  
FDA 
Notification within 30 working days and will include the 
reasons for any request that an investigator return, repair, 
or otherwise dispose of any devices.  
Study deviation  
Investigators 
Ensure that all deviations from the Clinical Investigation 
Plan are reviewed with the appropriate clinical 
investigator(s), are reported on the case report forms and 
the final report of the clinical investigation. (ISO 
14155:2011) 
Site specific study deviations will be submitted to 
investigators periodically.  
Device Deficiency 
(DD)  
Health Canada  
Any DD that: 
a. has resulted in any of the consequences 
characteristic of an SAE on the patient, the 
user or any other person; These must be 
reported by Medtronic to the Regulator 
within 10 days from the date Medtronic 
becomes aware. 
 
or 
b. could do so were it to reoccur. These must 
be reported by Medtronic to the Regulator 
within 30 days from the date Medtronic 
becomes aware. 
 
 
  
Table 13: Sponsor reports for Europe 
Report  
Submit to 
Description/Constraints 
Premature 
termination or 
suspension of the 
clinical investigation 
Investigators, 
IRB/MEC, 
Relevant 
authorities and 
Head of the 
Institution 
Provide prompt notification of termination or suspension 
and reason(s). 
Withdrawal of 
IRB/MEC approval 
Investigators, 
Head of 
Institution, 
IRB/MEC and  
relevant 
authorities 
Investigators, IRBs/MECs will be notified only if required by 
local laws or by the IRB/MEC. 
Withdrawal of CA 
approval 
Investigators, 
Head of 
Institution, 
IRB/MEC, and 
relevant 
authorities 
Investigators, IRBs/MECs will be notified only if required by 
local laws or by the IRB/MEC. 
Progress Reports 
IRB/MEC and 
regulatory 
authorities 
This will be submitted to the IRB/MEC only if required by 
the IRB/MEC. 

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Submit to 
Description/Constraints 
Final report 
Investigators,  
IRB/MEC, and 
Regulatory 
authorities upon 
request 
ISO 14155: 
The investigator shall have the opportunity to review and 
comment on the final report.  
If a clinical investigator does not agree with the final report, 
his/her comments shall be communicated to the other 
investigator(s).  
Study deviation  
Investigators 
Site specific study deviations will be submitted to 
investigators periodically.  
 
 
Table 14: Sponsor reports for the United States 
Report  
Submit to 
Description/Constraints 
Withdrawal of 
IRB/MEC approval 
Investigators, 
IRB/MEC, 
FDA, and 
relevant 
authorities 
Notification within five working days. (21 CFR 
812.150(b)(2))  
Progress Reports 
IRB/MEC  
Progress reports will be submitted at least annually. (21 
CFR 812.150(b)(5), 812.36(f)  
Recall and device 
disposition 
Investigators, 
Head of 
Institution, 
IRB/MEC, 
relevant 
authorities 
Notification within 30 working days and will include the 
reasons for any request that an investigator return, repair, 
or otherwise dispose of any devices. (21 CFR 
812.150(b)(6)) 
Failure to obtain 
informed consent  
IRB/MEC 
 
Investigator’s report will be submitted to FDA within five 
working days of notification. (21 CFR 812.150(b)(8)) 
Final report 
Investigators, 
IRB/MEC,  
Regulatory 
authorities upon 
request 
Medtronic will notify IRB/MEC within 30 working days of the 
completion or termination of the investigation. A final report 
will be submitted to IRB/MEC, investigators, and 
IRBs/MECs within six months after completion or 
termination of this study. (21 CFR 812.150(b)(7)) 
Study deviation  
Investigators 
Ensure that all deviations from the Clinical Investigation 
Plan are reviewed with the appropriate clinical 
investigator(s), are reported on the case report forms and 
the final report of the clinical investigation.  
Site specific study deviations will be submitted to 
investigators periodically.  
Other 
IRB 
Accurate, complete, and current information about any 
aspect of the investigation. (21 CFR 812.150(b)(10)) 
 
Medtronic records and reports will be maintained in a password-protected 
document management system, and paper documents (where applicable) will be 
stored in stored in secured file cabinets at Medtronic during the course of this 
study.  
 
After closure of the study Medtronic will archive records and reports for the Life of 
Product, with Life of Product defined as End of Production plus 15 years or the Life 
of Medical Device plus 1 year, whichever is longer. 

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Appendix A. 
Draft data collection elements (Case 
Report Forms) 
 
Draft Case Report Forms for the ECG Belt study may be provided under separate cover 
upon request. Final CRFs will be provided to sites via the electronic data management 
system after the site has fulfilled all requirements for database access. 
 
Appendix B. 
Preliminary publication plan 
 
Publications from the ECG Belt study will be handled according to Medtronic Standard 
Operating Procedures and as indicated in the Clinical Trial Agreement and the 
Publication Plan. 
Publication Committee 
Medtronic may form the ECG Belt Publication Committee from steering committee 
members and study investigators. Medtronic personnel may serve as members of the 
committee. This committee will manage study publications with the goal of publishing 
findings from the data. The Publication Committee will develop the final Publication Plan 
as a separate document.  
The Publication Committee’s role is to: 1) manage elements addressed in the publication 
plan as outlined in this appendix, 2) develop the final Publication Plan under separate 
cover, 3) execute the Publication Plan, 4) oversee the publication of primary, secondary 
and ancillary study results (as applicable), 5) review and prioritize publication proposals, 
6) provide input on publication content, and 7) determine authorship. In addition, the 
committee will apply and reinforce the authorship guidelines set forth in the Publication 
Plan.  
Membership in the Publication Committee does not guarantee authorship. The 
committee will meet as needed. 
 
Management of Primary, Secondary and Ancillary Publications 
The Publication Committee reviews, prioritizes, and manages all publications including 
primary, secondary and ancillary publications. Primary and secondary publications are 
those that address analyses of any or all primary objectives or secondary objectives, 
respectively, as specified in the Clinical Investigation Plan.  
An ancillary publication is any publication that does not address the study objectives 
identified in the Clinical Investigation Plan. They include publications proposed and 
developed by other Medtronic departments or entities, clinicians participating in this 
clinical study, and clinicians not participating in this clinical study. The committee will 
work with Medtronic to ensure that requests do not present conflicts with other 
proposals, are not duplicative, and to determine which ancillary publication proposals, if 
any, will be supported.  

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The committee may decide that no publications, including abstracts, will be published 
prior to the end of the study or with individual center data. Requests for publications on 
study objectives utilizing subset data (e.g., regional) will be evaluated for scientific 
validity and the ability of Medtronic to provide resources.  
 
Criteria for Determining Authorship and Contributorship 
Publications will adhere to authorship and contributorship criteria defined by the 
International Committee of Medical Journal Editors (ICMJE, Uniform requirements for 
manuscripts submitted to biomedical journals, www.icmje.org). Individual authorship and 
contributorship criteria defined by the target journal or conference will be followed when 
it differs from ICMJE criteria. 
Authors, including Medtronic personnel, must at a minimum meet all of the conditions 
below: 
• 
Substantial contribution to conception and design, or acquisition of 
data, or analysis and interpretation of data 
• 
Drafting the article or revising it critically for important intellectual 
content 
• 
Final approval of the version to be published 
• 
Agreement to be accountable for all aspects of the work in ensuring 
that questions related to the accuracy or integrity of any part of the 
work are appropriately investigated and resolved.  
 
Contributors, Medtronic personnel or Health Care Provider (HCP), may be considered 
for inclusion in an Acknowledgement section of the publication. Depending on degree, 
these contributions might merit contributorship in the publication.  
Decisions regarding authorship and contributorship will be made by the committee. The 
selected authors will be responsible for drafting the publication. All selected authors 
must fulfill the authorship conditions stated above to be listed as authors, and all 
contributors who fulfill the conditions must be listed as authors. 
All investigators not listed as co-authors will be acknowledged as the “Medtronic ECG 
Belt Clinical Study Investigators” and will be individually listed according to the 
guidelines of the applicable scientific journal when possible and affiliation. Any other 
contributors will be acknowledged by name with their specific contribution indicated. 
Transparency 
Transparency of study results will be maintained by the following means: 
• 
a final report, describing the results of all objectives and analysis, will 
be distributed to all investigators, ECs and Competent Authorities of 
participating countries when required by local law 
• 
registering and posting the study results on ClinicalTrials.gov based 
on the posting rules stipulated  
• 
submitting for publication the primary study results after the study 
ends  

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• 
disclosing conflicts of interest (e.g., financial) of the co-authors of 
publications according to the policies set forth by the corresponding 
journals and conferences  
• 
making an individual centers study data accessible to the 
corresponding investigator after the completion of the study, if 
requested 
 
 
Appendix C. 
Patient Informed Consent template 
 
Patient ICF template will be provided under separate cover 
 
Appendix D. 
Participating investigators and 
institutions 
 
A complete list of participating investigators and institutions where study activities will be 
conducted and the emergency contact details will be distributed under a separate cover 
when available. 
 
Appendix E. 
IRB/MEC and Competent Authority list 
 
A complete list of participating IRB/MECs and the Chairperson(s) will be distributed 
under a separate cover when available. 
 
Appendix F. 
Labeling 
 
Labeling and package for all products used in this study will follow the local regulatory 
requirements. In geographies where the market released products are commercially 
available, original device labeling will be used unless local regulations require otherwise.  
For components that are not market released or not commercially available and in 
geographies where investigational labeling is required for market released product used 
outside of approved indications, investigational labelling will be done as per local 
regulations.  
The various investigational components of the ECG Belt Research System used in this 
study, or their immediate package, shall bear a label with the following information: the 
name and place of business of the manufacturer, packer, or distributor, and the quantity 
of contents, as appropriate. 

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Labeling will be provided according to local law which may require translation to the local 
language. 
Product information (e.g. the ECG Belt Research System User Manual) will be provided 
in English unless required per local legislation to provide local language. 
 
United States 
The labeling of the investigational products shall include the statement: “CAUTION - 
Investigational Device. Limited by Federal law (U.S.A.) to investigational use” and 
describe all relevant contraindications, hazards, adverse effects, interfering substances 
or devices, warnings, and precautions. 
 
Canada  
The labeling of the investigational products shall include the statements: “Investigational 
Device” / “Instrument de recherche” and “To Be Used by Qualified Investigators Only” 
and “Réservé uniquement à l’usage de chercheurs compétents”, or any other 
statements, in English and French, that convey that meaning. 
 
Europe 
The labeling of the investigational products shall include the statement: “Exclusively for 
clinical investigations”, as applicable per local law. English labeling will be used for 
investigational devices unless otherwise required by local regulation. Labeling of CE-
Marked devices must follow local language requirements. 
 
 
 

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Appendix H. 
Clinical investigation plan signature page 
 
ECG Belt for CRT Response 
 
The ECG Belt study is a prospective, randomized (2:1:1), multi-center, investigational, 
research study. The study is being conducted to compare ECG Belt managed CRT 
patients and standard CRT with respect to chronic outcomes. ECG Belt will be used at 
implant and/or follow-up to guide LV lead placement (at implant) optimize pacing 
vector/timing parameters (during follow-up). 
 
Clinical Investigation Plan Version 5.0 – 02MAY2019 
 
I/we acknowledge that I/we have read, understood and agreed to abide by all conditions, 
instructions and restrictions contained in the above mentioned Clinical Investigation 
Plan. I/we agree to carry out all of its items in accordance with applicable regulations 
and in full compliance with the guidelines. 
 
 
 
 
Hospital  
City 
Country 
 
 
 
 
 
Title, First and last Name  
Signature  
Date (dd/MMM/yyyy) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Appendix I. 
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of Cardiac Resynchonization Therapy. Am J Cardiol. 2011;107(6):927-34.  
2 Birnie D, Lemke B, Anouma K, Krum H, et al. Clinical outcomes with synchronized left 
ventricular pacing: analysis of the adaptive CRT trial. Heart Rhythm, 2013; 10:1368-
1374. 
3 Gage RM, Curtin AE, Burns KV, Ghosh S, Gillberg JM, Bank AJ. Changes in electrical 
dyssynchrony by body surface mapping predict left ventricular remodeling in patients 
with cardiac resynchronization therapy. Heart Rhythm, 2017; 14(3):392-399. 
4 Duckett SG, Ginks M, Shetty AK, Bostock, J, Gill JS, Hamid S, Kapetanakis S, Cunliffe 
E, Razavi R, Carr-White G, Rinaldi A. Invasive acute hemodynamic response to guide 
left ventricular lead implantation predicts chronic remodeling in patients undergoing 
cardiac resynchronization therapy. J Am Coll Cardiol.2011; 58:1128-1136. 
5 Johnson WB, Vatterott PJ, Peterson MA, Bagwe S, Underwood RD, Bank AJ, Gage 
RM, Ramza B, Foreman BW, Splett V, Haddad T, Gillberg JM, Ghosh S. Body surface 
mapping using an ECG belt to characterize electrical heterogeneity for different left 
ventricular pacing sites during cardiac resynchronization: Relationship with acute 
hemodynamic improvement. Heart Rhythm, 2017; (14)3:385-391. 
6 Hamid S, Kapetanakis S, Cunliffe E, Razavi R, Carr-White G, Rinaldi A. Invasive acute 
hemodynamic response to guide left ventricular lead implantation predicts chronic 
remodeling in patients undergoing cardiac resynchronization therapy. J Am Coll 
Cardiol.2011; 58:1128-1136. 
7 A.J. Bank et al. Body surface activation mapping of electrical dyssynchrony in cardiac 
resynchronization therapy patients: Potential for optimization. J Electrocardiol 2018 May 
- Jun;51(3):534-541. 
8 Gage RM, et al. Twelve-Lead ECG Optimization of Cardiac Resynchronization 
Therapy in Patients With and Without Delayed Enhancement on Cardiac Magnetic 
Resonance Imaging. J Am Heart Assoc 2018 Dec;7(23):e009559. 
9 Sweeney MO, van Bommel RJ, Schalij MJ, Borleffs JW, Hellkamp AS, Bax JJ. 
Analysis of ventricular activation using surface electrocardiography to predict left 
ventricular reverse volumetric remodeling during cardiac resynchronization therapy. 
Circulation. 2010;121:626-634. 
10 Ramanathan C, Ghanem RN, Jia P, Ryu K, Rudy Y. Electrocardiographic Imaging 
(ECGI): A Noninvasive Imaging Modality for Cardiac Electrophysiology and Arrhythmia. 
Nature Medicine 2004; 10:422-428. 
11 Ghosh S, Rhee EK, Avari JN,  Woodard PK, Rudy Y. Cardiac Memory in WPW 
Patients: Noninvasive Imaging of Activation and Repolarization before and after Catheter 
Ablation. Circulation. 2008;118:907-915. 
12 Jia P, Ramanathan C, Ghanem RN, Ryu K, et al. Electrocardiographic imaging of 
cardiac resynchronization therapy in heart failure: observation of variable 
electrophysiologic responses. Heart Rhythm.2006;3:296-310. 
 
                                                 

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13 Ghosh S, Silva JNA, Canham RM, Bowman TM, Zhang J, Rhee EK, Woodard PK, 
Rudy Y. Electrophysiologic substrate and intraventricular left ventricular dyssynchrony in 
non-ischemic heart failure patients undergoing cardiac resynchronization therapy. Heart 
Rhythm. 2011;8:692-699. 
14 Xhaet O, Shah A, Linton N, et al. Noninvasive 3D electrical activation in heart failure 
patients with narrow QRS complexes. Heart Rhythm.2010; 7(5):S78. 
15 Ploux S, Xhaet O, Ramanathan C, et al. Electrocardiographic imaging for electrical 
asynchrony evaluation: insight into a new patient selection strategy. Heart Rhythm. 
2011; 8(5):S14. 
16 Rademakers LM, van Kerckhoven R, van Deursen CJM, et al. Myocardial Infarction 
Does Not Preclude Electrical and Hemodynamic Benefits of Cardiac Resynchronization 
Therapy in Dyssynchronous Canine Hearts. Circulation Arrhythmia and 
Electrophysiology.2010;3:361-368. 
17 Medtronic unpublished data on file. 
18 Martin DO, Lemke B, Birnie D, et al. Investigation of a novel algorithm for 
synchronized left ventricular pacing and ambulatory optimization of cardiac 
resynchronization therapy: results of the adaptive CRT trial. Heart Rhythm. 2012; 9(11): 
1807-1814. 
19 Daubert JC, Saxon L, Adamson PB, Auricchio A, et al. 2012 EHRA/HRS expert 
consensus statement on cardiac resynchronization therapy in heart failure: implant and 
follow-up recommendations and management. Heart Rhythm, 2012. 9:1524-1576. 
20 Birnie D, Lemke B, Aonuma K, Krum H, Lee KL, Gasparini M, Starling RC, 
Milasinovic G, Gorcsan J 3rd, Houmsse M, Abeyratne A, Sambelashvili A, Martin DO. 
Clinical outcomes with synchronized left ventricular pacing: analysis of the adaptive CRT 
trial. Heart Rhythm. 2013 Sep;10(9):1368-74 
21 Singh JP, Abraham WT, Chung ES, Rogers T, Sambelashvili A, Coles JA Jr, Martin 
DO. Clinical response with adaptive CRT algorithm compared with CRT with 
echocardiography-optimized atrioventricular delay: a retrospective analysis of 
multicentre trials. Europace. 2013; 15(11):1622-8. 
22 Gold MR, Daubert C, Abraham WT, Ghio S, Sutton MSJ, Hudnall JH, Cerkvenik J, 
Linde C. The effect of reverse remodeling on long-term survival in mildly symptomatic 
patients with heart failure receiving cardiac resynchronization therapy: Results of the 
REVERSE study. Heart Rhythm, 2015; 12(3):524-530.  
23 Packer M. Proposal for a new clinical end point to evaluate the efficacy of drugs and 
devices in the treatment of chronic heart failure J Card Fail. 2001; 2:176-82.