Conduction System Pacing Optimized Therapy Study
Phase: NA
Conditions: Heart Failure
Sponsor: Medtronic Cardiac Rhythm and Heart Failure

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DOCUMENT/RECORD 
 
 
This document/record is electronically controlled; printed copies are considered uncontrolled. 
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Title
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Monitor
Biostatistician
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05/02/2022 18:50:26
1.0
Medical Writer
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Randall, Taryn
CSPOT Clinical Iinvestigation Plan V4.0 29APR2022
Clinical Quality/Compliance
Rhoads, Neysa
05/02/2022 18:54:48
Aso, Joy
05/02/2022 16:32:18
05/02/2022 18:50:27
Gielkens, Manon
04/29/2022 20:02:57
Rose, Rachael
Tinsley, Jennifer
Document Approver
Clinical Study Manager (CSM)
04/30/2022 01:07:41
Zimmerman, Patrick
05/02/2022 12:48:17
Randall, Taryn
Palm, Kaitlyn
04/29/2022 20:50:57
04/29/2022 21:18:52
Safety
05/02/2022 18:50:27
Clinical Research Specialist
Rose, Rachael
Regulatory
CSPOT Clinical Iinvestigation Plan V4.0 29APR2022
Document Author

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Clinical Investigation Plan 
Clinical Investigation Plan/Study Title 
Conduction System Pacing Optimized Therapy 
(CSPOT) 
Clinical Investigation Plan Identifier 
MDT20029 
Study Product Name 
CSPOT Research System (an un-modified CRT 
device with off-label use lead placement) 
Sponsor/Local Sponsor and EU Legal 
representative 
Medtronic, Inc 
8200 Coral Sea Street NE 
Mounds View, MN U.S.A. 55112 
Phone: +1 800 328 2518 
Medtronic, Bakken Research Center B.V. 
Endepolsdomein 5, 6229 GW Maastricht, 
The Netherlands 
Phone: +31 43 3266566 
Document Version 
4.0, 29-Apr-2022 
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 
Table of Contents ......................................................................................................................... 2 
1. 
Administrative Information ..................................................................................................... 7 
1.1. Sponsor Contact Information.................................................................................................7 
1.2. Contract Research Organizations ...........................................................................................8 
1.3. Principal Investigator ............................................................................................................8 
2. 
Glossary .......................................................................................................................................... 9 
3. 
Synopsis ............................................................................................................................. 12 
Inclusion Criteria ....................................................................................................................... 14 
Exclusion Criteria ...................................................................................................................... 15 
4. 
Introduction ........................................................................................................................ 17 
4.1 Background ....................................................................................................................... 17 
4.2 Purpose ............................................................................................................................ 18 
5. 
Objectives and/or Endpoints ................................................................................................. 19 
5.1 Objectives ........................................................................................................................ 19 
5.1.1 
Primary Objective(s) ........................................................................................................... 19 
5.1.2 
Secondary Objective(s) ....................................................................................................... 19 
5.1.3 
Ancillary Objective .............................................................................................................. 20 
6. 
Study Design ....................................................................................................................... 20 
6.1 Duration ........................................................................................................................... 21 
6.2 Rationale .......................................................................................................................... 21 
6.3 Minimization of Bias ............................................................................................................ 22 
7. 
Product Description ............................................................................................................. 22 
7.1 General ............................................................................................................................ 22 
7.1.1 
Medtronic Compatible CRT-D/CRT-P Devices .................................................................. 24 
7.1.2 
ECG Belt System ................................................................................................................. 25 
7.1.3 
Millar Pressure Catheter and Connection Cable ................................................................. 25 
7.1.4 
Cardiotek EP System and 12 Lead ECG system ................................................................. 25 
7.1.5 
Threshold Cables................................................................................................................. 25 
7.1.6 
Medtronic External Pacer .................................................................................................... 25 

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7.1.7 
Pacing Leads ........................................................................................................................ 25 
7.2 Labeling....................................................................................................................................... 26 
7.3 Product Use ...................................................................................................................... 26 
7.4 Product Storage ................................................................................................................ 27 
7.5 Product Accountability........................................................................................................ 27 
7.6 Product Training Materials ................................................................................................... 28 
7.7 Product Return .................................................................................................................. 28 
8. 
Study Site Requirements ...................................................................................................... 28 
8.1 Investigator/Investigation Site Selection ............................................................................... 28 
8.2 Study Site Activation .......................................................................................................... 28 
8.3 Role of the Sponsor Representatives ..................................................................................... 29 
9. 
Selection of Subjects ............................................................................................................ 30 
9.1 Study Population................................................................................................................ 30 
9.2 Subject Enrollment ............................................................................................................. 30 
9.3 Inclusion Criteria ................................................................................................................ 30 
9.4 Exclusion Criteria ............................................................................................................... 30 
10. 
Study Procedures ............................................................................................................. 31 
10.1 Schedule of Events and Data Collection ................................................................................. 31 
10.2 Prior and Concomitant Medications/Therapies ....................................................................... 32 
10.3 Subject Consent ................................................................................................................ 32 
10.4 Enrollment ........................................................................................................................ 34 
10.5 Baseline ........................................................................................................................... 34 
10.6 CRT-D/CRT-P Implant ........................................................................................................ 35 
10.6.1 
CSPOT Acute Pacing Protocol ............................................................................................ 35 
10.6.2 
CSPOT Chronic Final Device Programming ........................................................................ 38 
10.7 Scheduled Follow-up Visits .................................................................................................. 39 
10.7.1 
6-Month In-Office Follow Up Visit ...................................................................................... 40 
10.7.2 
Study Exit ............................................................................................................................ 40 
10.7.3 
Lost to Follow-up ................................................................................................................ 41 
10.7.4 
Subject Chooses to Exit (i.e., Revokes Consent) ................................................................ 42 

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10.7.5 
Investigator Withdraws Subject .......................................................................................... 42 
10.8 Device Interrogation........................................................................................................... 42 
10.9 System Modification ........................................................................................................... 42 
10.10 
Medication Assessment ............................................................................................... 43 
10.11 
Assessment of Safety .................................................................................................. 43 
10.12 
Recording Data ........................................................................................................... 43 
10.13 
Deviation Handling ...................................................................................................... 45 
11. 
Risks and Benefits ............................................................................................................ 46 
11.1 Potential Risks ................................................................................................................... 46 
11.2 Risk Minimization ............................................................................................................... 47 
11.3 Potential Benefits .............................................................................................................. 50 
11.4 Risk-Benefit Rationale......................................................................................................... 50 
12. 
Adverse Events and Device Deficiencies .............................................................................. 50 
12.1 Adverse Events ................................................................................................................. 50 
12.2 Device Deficiency .............................................................................................................. 50 
12.3 Processing Updates and Resolution ....................................................................................... 51 
12.4 Definitions/Classifications ................................................................................................... 51 
12.5 Reporting of Adverse Events and Device Deficiencies ............................................................... 57 
12.5.1 
Adverse Event and Device Deficiency Collection ............................................................... 57 
12.5.2 
Adverse Event and Device Deficiency Classification.......................................................... 58 
12.5.3 
Adverse Event and Device Deficiency Reporting Requirements ....................................... 59 
12.6 Subject Death ................................................................................................................... 61 
12.6.1 
Death Classification and Reporting .................................................................................... 61 
12.7 Product Complaint Reporting ............................................................................................... 62 
13. 
Data Review Committees .................................................................................................. 63 
13.1 Clinical Events Committee ................................................................................................... 63 
14. 
Statistical Design and Methods .......................................................................................... 64 
14.1 General Aspects of Analysis ................................................................................................. 64 
14.2 Analysis Execution ............................................................................................................. 65 
14.3 Interim Analysis ................................................................................................................. 65 

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14.4 Primary Objectives ............................................................................................................. 65 
14.4.1 
Primary Objective #1 .......................................................................................................... 65 
14.4.2 
Primary Objective #2 .......................................................................................................... 65 
14.5 Secondary Objectives ......................................................................................................... 66 
14.5.1 
Secondary Objective #1 ..................................................................................................... 66 
14.5.2 
Secondary Objective #2 ..................................................................................................... 66 
14.5.3 
Secondary Objective #3 ..................................................................................................... 67 
14.5.4 
Secondary Objective #4 ..................................................................................................... 67 
14.5.5 
Secondary Objective #5 ..................................................................................................... 67 
14.6 Ancillary Objective (Adverse Events) ..................................................................................... 67 
14.7 Additional Data Collection ................................................................................................... 68 
14.8 Sample Size Determination.................................................................................................. 68 
15. 
Ethics ............................................................................................................................. 68 
15.1 Statement(s) of Compliance ................................................................................................ 68 
16. 
Study Administration ....................................................................................................... 69 
16.1 Monitoring ........................................................................................................................ 69 
16.1.1 
Monitoring Visits ................................................................................................................. 69 
16.2 Data Management .............................................................................................................. 70 
16.3 Direct Access to Source Data/Documents ............................................................................. 71 
16.4 Confidentiality ................................................................................................................... 71 
16.5 Liability/Warranty/Insurance Information ............................................................................... 71 
16.5.1 
Warranty .............................................................................................................................. 71 
16.5.2 
Insurance (Europe) .............................................................................................................. 71 
16.6 CIP Amendments ............................................................................................................... 72 
16.7 Record Retention ............................................................................................................... 72 
16.7.1 
Investigator Records ........................................................................................................... 72 
16.7.2 
Sponsor Records ................................................................................................................. 73 
16.8 Reporting Requirements ..................................................................................................... 74 
16.8.1 
Investigator Reports ........................................................................................................... 74 
16.8.2 
Sponsor Reports ................................................................................................................. 77 

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16.9 Publication and Use of Information ........................................................................................ 78 
16.9.1 
Publication Committee ....................................................................................................... 78 
16.9.2 
Management of Primary, Secondary, and Ancillary Publications ........................................ 79 
16.9.3 
Criteria for Determining Authorship ................................................................................... 79 
16.9.4 
Transparency ...................................................................................................................... 80 
16.10 
Suspension or Early Termination .................................................................................... 80 
16.10.1 
Planned Study Closure .................................................................................................... 80 
16.10.2 
Early Termination or Suspension .................................................................................... 80 
16.10.3 
Procedures for Termination or Suspension .................................................................... 81 
17. 
References ...................................................................................................................... 82 
18. 
Appendices ..................................................................................................................... 83 
18.1 Informed Consent Template ............................................................................................... 83 
18.2 Data Collection Elements (Electronic Case Report Forms) ...................................................... 83 
18.3 Participating Investigators and Institutions .......................................................................... 83 
18.4 IRB Committee List ........................................................................................................... 83 
18.5 Committees ................................................................................................................................ 83 
18.6 Labeling ........................................................................................................................... 84 
18.7 Foreseeable Adverse Events List (FAL) ................................................................................ 84 
18.7.1 
Observed Adverse System Effects in Previous Clinical Studies and Adverse Events 
Reported in Literature ........................................................................................................................ 84 
19. 
Version History ................................................................................................................ 86 

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1. Administrative Information 
 
 
1.1. Sponsor Contact Information 
Medtronic contact information is provided below. This information is subject to change during the 
clinical study. Periodic updates to study contact information will be sent to the sites as needed. 
 
Table 1: Sponsor Contact Information 
 
Study Manager Contacts 
Worldwide clinical study leader/US contact 
Rachael Rose, Pr. Clinical Research Specialist 
 
Europe clinical study leader/OUS contact 
Fabio Pradella, Clinical Research 
Specialist 
 
 
Monitoring Contacts 
Worldwide monitoring leader/US contact 
Taryn Randall, Clinical Monitoring Manager 
 
 
Monitoring leader Europe 
Anja Hesse, Prin. Clinical Research Monitor 

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1.2. Contract Research Organizations 
CRO information is provided below. This information is subject to change during the clinical study. 
Periodic updates to CRO information will be sent to the sites as needed. 
 
Table 2: CRO Information 
 
Contact Information 
Duties performed 
Cognizant Technology Solutions 
500 Frank W. Burr Blvd. 
Teaneck, NJ 07666 
United States 
Direct Phone: +1 201 801-0233 
Direct Fax: +1 201 801-0243 
• 
Development of study electronic case report forms, edit 
checks, and study management reports. 
• 
Review of electronic case report forms, management of 
discrepancies of data collection, and coding of deviations. 
 
 
1.3. Principal Investigator 
Overall study Principal Investigator and Steering Committee member contact information is provided 
below. Periodic updates to Principal Investigator information will be sent to the sites as needed. 
 
Table 3: Overall Study Principal Investigator Contact Information 
 
Name 
Contact Information 
Gaurav Upadhyay, MD 
University of Chicago 
119th E 18th St 
Chicago, IL 60605 
United States 
 

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2. Glossary 
 
Term 
Definition 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
ASADE 
Anticipated Serious Adverse Device Effect 
AF 
Atrial Fibrillation 
AFL 
Atrial Flutter 
AV Block 
Atrioventricular Block 
AV Delay 
Atrioventricular Delay 
CA 
Competent Authority 
CEC 
Clinical Events Committee 
CFR 
Code of Federal Regulation 
CIP 
Clinical Investigation Plan 
CRO 
Contract Research Organization 
CRT-D 
Implantable Cardioverter Defibrillator with Cardiac 
Resynchronization Therapy 
CRT-P 
Implantable Pulse Generator with Cardiac 
Resynchronization Therapy 
CRF 
Case Report Form 
CSP 
Conduction System Pacing 
CSPOT 
Conduction System Pacing, Optimized Therapy 
CTA 
Clinical Trial Agreement 
CV 
Curriculum Vitae 
DD 
Device Deficiency 
DMC 
Data Monitoring Committee 

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Term 
Definition 
DoH 
Declaration of Helsinki 
DTL 
Delegated Task List 
eCRF 
Electronic Case Report Form 
EC/IRB/HREB/Ethics Board 
Ethics Committee 
ECG Belt 
Electrocardiogram Belt 
FAL 
Foreseeable Adverse Events List 
FD 
Financial Disclosure 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator Brochure 
IC 
Informed Consent 
ICD 
Implantable Cardioverter Defibrillator 
ICH 
International Conference of Harmonization 
IDE 
Investigational Device Exemption 
IFU 
Instructions For Use 
IPG 
Implantable Pulse Generator 
IVCD 
Intraventricular Conduction Delay 
LBBB 
Left Bundle Branch Block 
LBBP 
Left Bundle Branch Pacing 
LV 
Left Ventricle 

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Term 
Definition 
LVEF 
Left Ventricular Ejection Fraction 
LVESV 
Left Ventricular End Systolic Volume 
MDD 
Medical Device Directive 
MDR 
Medical Device Regulation (EU) 
MedDRA 
Medical Dictionary for Regulatory Activities 
MHRA 
Medicines and Healthcare products Regulatory 
Agency (UK) 
MI 
Myocardial infarction 
PHI 
Protected Health Information 
RA 
Right Atrium 
RBBB 
Right Bundle Branch Block 
RPI 
Report of Prior Investigations 
RV 
Right Ventricle 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SC 
Steering Committee 
SID 
Subject Identification 
UAE 
Unavoidable Adverse Event 
UADE 
Unanticipated Adverse Device Effect 
USADE 
Unanticipated Serious Adverse Device Effect 
VV-Delay 
Ventricle to Ventricle Delay 

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3. Synopsis 
 
Title 
Conduction System Pacing Optimized Therapy (CSPOT) 
Clinical Study Type 
Prospective, non-randomized, multi-center, global, feasibility clinical study 
Product Name 
CSPOT Research System (an un-modified CRT device with off label use lead 
placement) 
Sponsor 
Sponsor: 
Medtronic, Inc 
8200 Coral Sea Street NE 
Mounds View, MN U.S.A. 55112 
Phone: +1 800 328 2518 
Local Sponsor: 
Medtronic, Bakken Research Center B.V. 
Endepolsdomein 5, 6229 GW Maastricht, 
The Netherlands 
Phone: +31 43 3266566 
External 
Organizations 
Cognizant Technology Solutions 
500 Frank W. Burr Blvd. 
Teaneck, NJ 07666 
United States 
Direct Phone: +x 201 801 0233 
Direct Fax: +x 201 801 0243 
Indication under 
investigation 
The CSPOT pacing system is utilizing a market approved CRT device and market 
approved leads to compare off-label methods of pacing: CSP (LBBP) and the 
combination of CSP +LV. 
Investigation 
Purpose 
The purpose of the CSPOT study is to determine the best mode of CRT pacing for 
different populations of CRT patients, comparing traditional BiV, CSP-only, and 
CSPOT (CSP+LV) pacing.  Additionally, safety of the system will be assessed. 

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Product/System 
Power isolation transformer 
as needed 
Cardiotek EP Recording System 
Study Objective 
Primary Objectives: 
1. Compare the electrical synchronization response of CSPOT pacing 
configuration to CSP-only and traditional CRT (See section 10.7.1) in 
patients undergoing a CRT implant, using the SDAT ECG-belt metric. 
2. Compare the hemodynamic response of a CSPOT pacing configuration to 
CSP-only and traditional CRT in patients undergoing a CRT implant, using 
the contractility parameter positive LV dP/dt max. 
Secondary Objectives: 
1. For each pacing configuration (CSP-only, traditional CRT, and CSPOT), 
summarize the improvement in the ECG Belt SDAT measurement 
relative to baseline at implant, for the following subpopulations: 
a. Subjects with QRS width < 150ms and those with QRS width >= 
150ms, as measured by 12-lead ECG at implant 
b. Subjects with pure LBBB and those with other conduction disorders 
c. Subjects with ischemic cardiomyopathy and those with non- 
ischemic cardiomyopathy 
2. For each pacing configuration (CSP-only, traditional CRT, and CSPOT), 
summarize the improvement in the contractility parameter positive LV 
dP/dt max relative to baseline at implant, for the following 
subpopulations: 
a. Subjects with QRS width < 150ms and those with QRS width >= 
150ms, as measured by 12-lead ECG at implant 

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c.    Subjects with ischemic cardiomyopathy and those with non- 
ischemic cardiomyopathy 
3. Characterize the chronic clinical response from CSPOT pacing by 
comparing LVEF measured at baseline to that measured at 6 months 
4. Characterize the chronic clinical response from CSPOT pacing by 
comparing LVESV measured at baseline to that measured at 6 months 
5. Characterize the chronic clinical response from CSPOT pacing by 
determining the Clinical Composite Score [1, 2] at 6 months 
Study Design 
The CSPOT study is a prospective, non-randomized, multi-center, global, 
feasibility clinical study. All enrolled subjects will undergo the CSPOT system 
protocol to obtain patient-specific optimal CRT therapy and then implanted with a 
market approved CRT device. Each subject will be programmed in their patient- 
specific CSPOT (CSP+LV) configuration and patients will be followed up for 6 
months or until official study closure, defined as when Medtronic and/or regulatory 
requirements have been satisfied per the Clinical Investigation Plan and/or by a 
decision by Medtronic or regulatory authority, whichever occurs first. 
 
 
 All adverse 
events (AEs) will be collected throughout the study duration of a subject’s 
participation in the study, beginning at the time of informed consent. 
Sample Size 
The study is expected to be conducted at up to 12 sites in the United States and 
Europe and up to 60 subjects will be enrolled with no more than 15 subjects 
enrolled per site. 
Inclusion/Exclusion 
Criteria 
Inclusion Criteria 
• 
Patient is willing and able to provide written informed consent 
• 
Subject is at least 18 years of age 
• 
Patient is willing and able to comply with the protocol, including follow-up 
visits 
• 
The patient’s medical records must be accessible by the enrolling site over 
the follow-up period 
• 
Standard CRT-D or CRT-P indications, with a preference for IVCD and non- 
LBBB patients, where LBBB is defined according to Strauss criteria. 
• 
De-novo CRT implant, including upgrade from pacemaker or ICD 

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Exclusion Criteria 
• 
Subject has persistent or permanent AF (Atrial Fibrillation)/AFL (Atrial 
Flutter) 
• 
Subject has 2nd or 3rd degree AV (Atrioventricular) Block 
• 
Subject has RBBB with no additional conduction block 
• 
Subject has intrinsic (non-paced) QRS width less than or equal to 120 
ms 
• 
Subject experienced MI within 40 days prior to enrollment 
• 
Subject underwent valve surgery, within 90 days prior to enrollment 
• 
Subject is post heart transplantation or is actively listed on the 
transplantation list 
• 
Subject is implanted with a LV assist device 
• 
Subject has severe renal disease 
• 
Subject is on continuous or uninterrupted infusion (inotropic) therapy 
for heart failure 
• 
Subject has severe aortic stenosis (with a valve area of <1.0 cm or 
significant valve disease expected to be operated within study period) 
• 
Subject has severe aortic calcification or severe peripheral arterial 
disease 
• 
Subject has complex or repaired congenital heart disease 
• 
Subject has mechanical heart valve 
• 
Pregnant or breastfeeding woman (pregnancy test required for woman 
of child-bearing potential and who are not on a reliable form of birth 
regulation method or abstinence) 
• 
Subject is enrolled in another study that could confound the results of 
this study without documented pre-approval from Medtronic study 
manager 
Study Procedures 
and Assessment 
STUDY PROCEDURE 
Baseline 
(occur within 30 
days prior to 
enrollment) 
Implant 
(occur within 30 
days after 
enrollment) 
6 month follow 
up and Study 
Exit 
Patient Informed Consent 
X 
Inclusion/Exclusion Assessment 
X 
Demographics 
X 
Medical History 
X 
Physical Exam 
X 
X 

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Medication Assessment 
X 
X 
Baseline 12-Lead ECG (within 60 days prior to 
X 
enrollment/consent) 
Baseline Echocardiography including LVEF and LVESV (within 
X 
60 days prior to enrollment/consent) 
NYHA 
X 
X 
ECG Belt 
X 
Lead Placement 
X 
CSPOT Research System Protocol 
X 
Insertion procedure information 
X 
Fluoroscopic Images of final LBBP lead placement 
X 
Patient Global Assessment 
X 
6 Month Echocardiography including LVEF and LVESV (within 
X 
30 days prior to visit) 
6 Month 12-Lead ECG (within 30 days prior to visit) 
X 
Final device programming 
X 
X 
Initial and Final Device Interrogation (with either initial or final 
X 
X 
interrogate ALL) and collect .pdd file 
Adverse Events 
Hospitalizations 
Death 
As they occur 
Device Deficiency 
System Modification 
Study Deviations 
Safety 
Assessments 
All adverse events (AEs) and device deficiencies will be collected throughout the 
study duration of a subject’s participation, beginning at the time of informed 
consent. An independent Clinical Event Committee (CEC) will conduct a medical 
review and adjudicate at a minimum all CRT-D/CRT-P system and procedure- 
related adverse events, all CSPOT system and procedure-related adverse events, 
all cardiovascular related AEs (regardless of seriousness), all SAEs and all AEs with a 
fatal outcome. The CEC will consist of non-Medtronic employed physicians that 
are not participating investigators for the study. 
Statistics 
A sample size of up to 60 subjects will be enrolled to determine the pacing 
configuration that provides better acute electrical synchrony and hemodynamic 
response. 
Additional sub-analyses will be performed to assess whether sub-populations 
derive benefit from different configurations. 

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4. Introduction 
 
 
4.1 Background 
The current standard-of-care therapy for heart failure patients with wide QRS is cardiac 
resynchronization therapy (CRT), which is commonly accomplished through biventricular pacing. His 
Bundle pacing may benefit some CRT patients as a replacement for biventricular pacing [3-6]. 
However, His Bundle pacing will not resynchronize some CRT patients that have conduction block 
distal to the His Bundle pacing location. In an effort to increase the benefit of His Bundle pacing for CRT 
patients, three studies suggested that the combination of His Bundle pacing with LV pacing 
(sometimes called “HOT-CRT”) provided improved clinical outcome [7-9]. Nevertheless, His Bundle 
pacing frequently suffers from high and unstable pacing thresholds and remains a challenging 
procedure. 
 
A different form of conduction system pacing (CSP), left bundle-branch pacing (LBBP), was introduced 
in 2017 [10]. LBBP has lower and more stable pacing thresholds than His Bundle pacing and is generally 
considered to be a simpler procedure.  Several studies have shown that LBBP is promising as an 
alternative to BiV pacing in CRT patients [11-13].  However, it appears that, like His pacing, some CRT 
patients will not receive adequate resynchronization from LBBP alone. These CRT patients may have 
more diffuse conduction disease, such as a combination of left bundle-branch block (LBBB) and 
intraventricular conduction delay (IVCD). Two studies have provided pilot data that the combination of 
LBBP and LV pacing (now referred to as “CSPOT” pacing) may improve resynchronization in some 
LBBP patients [12, 13]. These studies encourage further study of LBBP and CSPOT pacing in CRT 
patients, with emphasis on comparing the degree of resynchronization from each kind of pacing 
therapy and on determining the types of patients that benefit from each kind of pacing therapy. A 
summary/evaluation of the results of the pre-clinical testing can be found in the IB (Investigator 
Brochure). 
 
The CSPOT study therefore aims to compare three modes of resynchronization pacing: 1) traditional 
CRT (BiV or LV-only pacing), 2) LBBP, and 3) CSPOT (CSP+LV).  The study will collect three acute 
measures of resynchronization: 1) Mechanical measures of resynchronization via LV pressure, 2) 
Electrical measures of resynchronization via the ECG Belt, and 3) Electrical measures of 
resynchronization via the 12-lead ECG. 
 
The schematic below provides an overview of the CSPOT system. 

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Figure 1: CSPOT Research System 
 
 
 
4.2 Purpose 
Medtronic, Inc is sponsoring the CSPOT study, a prospective, non-randomized, multi-center, global, 
feasibility clinical study in the CRT patient population. The purpose of this study is to determine the 
best mode of CRT pacing for different populations of CRT patients, comparing traditional CRT (BiV or 
LV-only pacing), CSP-only, and CSPOT pacing. 
 
The CSPOT (Conduction System Pacing Optimized Therapy) Research System is being developed to 
support pre-market research comparing the acute effects of several different modalities of cardiac 
resynchronization pacing and to collect data for use in future algorithm development.  CSP, specifically 
LBBP, may provide superior resynchronization compared to traditional CRT pacing.  A subset of 
patients may further benefit from the combination of traditional LV pacing and CSP.  The CSPOT 
Research System will allow collection of ECG, EGM, LV pressures and ECG Belt dyssynchrony metrics 
during periods of traditional CRT pacing (BiV or LV-only pacing), CSP-only (i.e. LBB) pacing and CSP+LV 
pacing.  Findings from this feasibility study may be used as design inputs in developing a new system 
based on this technology. No long-term data using the research system will be collected. 
The CSPOT Research System is investigational and not intended for market release. 
 
 
 
as needed
 

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5. Objectives and/or Endpoints 
 
5.1 Objectives 
This prospective, non-randomized, multi-center, global, feasibility clinical study is designed to assess 
augmentation of electrical resynchronization as measured by ECG-belt metrics and 12-lead ECG, and 
to assess augmentation of contractility as measured by positive LV dP/dt max across LV pacing site(s) 
in patients indicated for CRT. 
 
Thereto, the SDAT metric from ECG Belt and the force of contraction during CSP or CSPOT pacing will 
be compared to that of standard CRT pacing. 
 
 In addition, the chronic 
electrical and clinical response will be investigated. Rationale for study design is to aim for maximizing 
the acute electrical and hemodynamic response on a per-patient basis, therefore the primary endpoint 
is written to satisfy comparing the response of CSPOT, the investigational system to traditional CRT 
pacing. 
5.1.1    Primary Objective(s) 
The primary objectives of the study are: 
 
1. Compare the electrical synchronization response of CSPOT pacing configuration to CSP-only 
and traditional CRT (See section 10.7.1) in patients undergoing a CRT implant, using the SDAT 
ECG-belt metric. 
2. Compare the hemodynamic response of a CSPOT pacing configuration to CSP-only and 
traditional CRT in patients undergoing a CRT implant, using the contractility parameter positive 
LV dP/dt max. 
 
5.1.2 Secondary Objective(s) 
The secondary objectives of the study are: 
 
1. For each pacing configuration (CSP-only, traditional CRT, and CSPOT), summarize the 
improvement in the ECG Belt SDAT measurement relative to baseline at implant, for the 
following subpopulations: 
a. Subjects with QRS width < 150ms and those with QRS width >= 150ms, as measured by 
12-lead ECG at implant 
b. Subjects with pure LBBB and those with other conduction disorders 
c.    Subjects with ischemic cardiomyopathy and those with non-ischemic cardiomyopathy 
2. For each pacing configuration (CSP-only, traditional CRT, and CSPOT), summarize the 
improvement in the contractility parameter positive LV dP/dt max relative to baseline at 
implant, for the following subpopulations: 
a. Subjects with QRS width < 150ms and those with QRS width >= 150ms, as measured by 

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12-lead ECG at implant 
b. Subjects with pure LBBB and those with other conduction disorders 

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c.    Subjects with ischemic cardiomyopathy and those with non-ischemic cardiomyopathy 
 
3. Characterize the chronic clinical response from CSPOT pacing by comparing LVEF measured at 
baseline to that measured at 6 months 
4. Characterize the chronic clinical response from CSPOT pacing by comparing LVESV measured 
at baseline to that measured at 6 months 
5. Characterize the chronic clinical response from CSPOT pacing by determining the Clinical 
Composite Score [1, 2] at 6 months. 
5.1.3 Ancillary Objective 
 
 
    
 
 
 
 
6. Study Design 
 
 
CSPOT is a prospective, non-randomized, multi-center, global, feasibility clinical study designed to 
assess different approaches to resynchronization in CRT-indicated patients and to support pre- 
market research comparing the acute effects of several different modalities of cardiac 
resynchronization pacing and to collect data for use in future algorithm development.   The study may 
enroll up to 60 subjects at up to 12 sites in the US, UK, and Europe with no more than 15 subjects 
enrolled per site.  Study subjects will be followed for 6 months or until official study closure, defined as 
satisfaction of Medtronic and/or regulatory requirements (per the Clinical Investigation Plan) and/or by 
a decision by Medtronic or regulatory authority, whichever occurs first. 
 
 
All adverse events (AEs) and device deficiencies will be 
collected throughout the study duration of a subject’s participation in the study, beginning at the time 
of informed consent. 
Following consent, subjects will undergo a baseline assessment followed by the CSPOT lead placement 
procedure, which will include the CSPOT Study Protocol. Each patient will serve as their own control. 
This will be considered the acute phase. Following the CSPOT study protocol procedure, the CRT- 
D/CRT-P device will be implanted. Each subject will be programmed to their patient specific CSPOT 
(CSP+LV) configuration and patients will be followed for 6 months. At the 6-month time point,  
electrical characterization will be performed via a 12-lead ECG and clinical endpoints will be collected to 
assess the chronic efficacy of CSPOT. 
 
 Subjects will be exited upon the completion of the 6-month visit. A study flowchart is shown  
in Figure 2. 

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Figure 2: Study Flowchart 
 
 
 
 
 
 
 
 
6.1 Duration 
 
Study subjects will be followed for 6 months or until official study closure, defined as satisfaction of 
Medtronic and/or regulatory requirements (per the Clinical Investigation Plan) and/or by a decision by 
Medtronic or regulatory authority, whichever occurs first. 
 
6.2 Rationale 
The CSPOT feasibility study employs a prospective, non-randomized, multi-center, global, design 
aimed at optimizing cardiac resynchronization pacing.  This study is intended to contribute to our 
understanding of optimal electrical synchrony and hemodynamics from different pacing 
configurations in patients who are indicated and implanted with a CRT-D/CRT-P.  
 
The CSPOT study will focus on optimizing pacing while posing minimal risk to the patient. 
 
 
 
 
 
 
 
 
 
 
Study Closure 

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After completion of this risk management activity and incorporation of the appropriate mitigations 
called out in this document, all identified risks have been mitigated to an acceptable level. 
6.3 Minimization of Bias 
Selection of subjects, treatment of subjects, and evaluation of study data are potential sources of bias. 
 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• 
 
 
 
 
 
 
7. Product Description 
 
 
7.1 General 
The CSPOT Research System will include both market approved and investigational components 
that will allow collection of ECG, EGM, LV pressure and electrical dyssynchrony metrics during 
periods of CRT pacing, CSP-only pacing, and CSP+LV pacing. 
 
Table 4 below identifies the market approved Medtronic devices that are compatible with the 
CSPOT Research System.  All CRT-P/CRT-D devices will be considered investigational during the 

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course of the study. The CSPOT system also includes several components that include both 
market approved, and investigational components identified in Table 5. 
Instructions for intended use, maintenance and calibration detail (if applicable), including 
indications and contraindications of the devices and components used in this study, as well as 
medical procedures and information regarding material in contact with tissues or body fluids, are 
provided in their respective manuals. 
 
 
 
Table 4: CSPOT System Compatible Devices 
 
Device Name 
Model Number(s) 
Market Released 
 
Percepta TM Quad CRT-P MRI SureScanTM 
W4TR01 
Market released 
W4TR04 
(available in Europe) 
Market released 
Serena TM   Quad CRT-P MRI SureScanTM 
W4TR02 
Market released 
W4TR05 
(available in Europe) 
Market released 
Solara TM   Quad CRT-P MRI SureScanTM 
W4TR03 
Market released 
W4TR06 
(available in Europe) 
Market released 
 
Viva TM   Quad S CRT-D 
DTBB1Q1 
Market released 
DTBB2Q1 
(available in Europe) 
Market released 
Viva TM   Quad XT CRT-D 
DTBA1Q1 
Market released 
DTBA2Q1 
(available in Europe) 
Market released 
 
Brava Quad XT CRT-D 
DTBC1Q1 
Market released 
DTBC2Q1 
(available in Europe) 
Market released 
Claria MRITM Quad CRT-D 
DTMA1Q1 
Market released 
DTMA2Q1 
(available in Europe) 
Market released 
Amplia MRI TM Quad CRT-D 
DTMB1Q1 
Market released 
DTMB2Q1 
(available in Europe) 
Market released 
Cobalt TM XT Quad CRT-D MRI SureScanTM 
DTPA2Q1 
Market released 

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CobaltTM HF Quad CRT-D MRI SureScanTM 
DTPB2Q1 
Market released 
CromeTM HF Quad CRT-D MRI SureScanTM 
DTPC2Q1 
Market released 
 
 
 
Table 5: CSPOT Research System Components 
 
Model Number(s) 
Component 
Manufacturer 
Investigational or Market- 
released 
EA1B5S, EA1B5L (Belt) 
EA1A (amplifier) 
EA1T (tablet) 
ECG Belt System 
Medtronic 
Investigational 
825-0101 
Millar Pressure Catheter 
Millar 
Market-Released 
850-5148 
Millar Connection Cable 
Millar 
US: Investigational 
OUS: Market-Released 
00EPT01 
Cardiotek EP-Tracer 38 System 
Cardiotek 
Market-Released 
N/A 
Threshold Cable 
Any manufacturer 
Market-Released 
5392 
Medtronic External Pacer 
Medtronic 
Market-Released 
3830 SelectSecure 
Medtronic Pacing Leads 
Medtronic 
Investigational when used in the 
study (due to implant location) 
LV Quad polar leads: 
4298, 4398, 4598 (Attain 
Performa) 
4798 (Attain Stability) 
Medtronic Pacing Leads 
Medtronic 
Market-Released 
N/A 
RA bipolar lead 
Any manufacturer 
Market-Released 
RV defibrillation lead with 
IS1/DF1 connector: 
6935 (Sprint Quattro single 
coil) 
6947 (Sprint Quattro dual 
coil) 
Medtronic Defibrillation Leads 
Medtronic 
Market-Released 
CRT P Quad and CRT-D 
Quad w/DF-1 Connector 
Models (see Table 4) 
Medtronic CRT devices 
Medtronic 
Market-Released 
 
7.1.1 Medtronic Compatible CRT-D/CRT-P Devices 
Any device compatible with the CSPOT Research System (outlined in Table 4 above) can be used in this 
study. CRT-D devices are indicated for providing cardiac resynchronization therapy in heart failure 
subjects and ventricular anti-tachycardia pacing and ventricular defibrillation for automated treatment 
of life-threatening ventricular arrhythmias.  CRT-P devices are indicated for providing cardiac 
resynchronization therapy in heart failure subjects. In addition, these devices can be used in subjects 

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with atrial tachyarrhythmias, or those subjects who are at significant risk for developing atrial 
tachyarrhythmias. All devices should be implanted as per the current AHA/ACC/HRS Guideline [14]. The 
CRT-D/CRT-P devices used in the study are market released but are considered investigational during 
the course of the study. 
 
7.1.2 ECG Belt System 
 
 
 
 
7.1.3 Millar Pressure Catheter and Connection Cable 
The Millar pressure catheter measures continuously the LV pressure and is market released. The 
connection cable for the catheter transmits the LV pressure data to the recording system and is 
considered investigational in the US only (i.e. CE-labeled for EMEA). 
 
7.1.4 Cardiotek EP System and 12 Lead ECG system 
The Cardiotek system will deliver either traditional CRT pacing, CSP-only pacing, or CSPOT pacing at 
different AV and VV intervals based on the trigger signal from the EPG.  The Cardiotek EP system 
acquires and stores time-aligned ECG, EGM and LV pressure. It provides a configurable electrical 
connection for up to 4 leads and the pocket and provides synchronized pacing of selected lead 
configurations, including control of pacing amplitude, pulse width and relative timing. 
 
The 12-Lead ECG is a standard configuration of 12 leads to understand the heart’s electrical activity. A 
standard 12-lead ECG (supplied by Cardiotek) is connected to a Cardiotek EP recorder system will allow 
measurement of the necessary timing intervals. 
7.1.5 Threshold Cables 
Threshold cables are used during the CSPOT acute protocol. They are used for the connections 
between the Cardiotek device and the leads. Any market-released single model lead cables may be 
used that are compatible with the CSPOT Research system.  Compatible models can be found in the 
CSPOT System User Manual.   In addition, instead of a single cable, two connected cables (e.g. Oscor 
ATAR D-R and Oscor ATAR D-V2) that meet the above may be used. 
7.1.6 Medtronic External Pacer 
A Medtronic External Pulse Generator Model 5392 will be configured to provide atrial pacing and to 
trigger the Cardiotek system. The external pacer is a temporary pacer that allows atrial pacing, 
including control of the amplitude and rate. 
 
7.1.7 Pacing Leads 
Medtronic compatible (refer to Table 5 above) commercially available transvenous leads CSP, RV and 
LV are required to be used in the study. Any commercially available RA lead can be used in the study. 
Every subject’s CRT system shall include the following leads: 
• 
Right atrial pacing lead 

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• 
Left ventricular pacing lead 
• 
Right ventricular defibrillation lead (CRT-D only) 
• 
Conduction system pacing lead (Model 3830) 
 
1. Right Atrial Leads 
Any commercially available RA lead 
 
2. Left Ventricular Leads 
Medtronic commercially available LV transvenous pacing leads are required. 
 
3. Right Ventricular Leads 
Medtronic commercially available RV pacing or defibrillation (for CRT-D) leads are required. 
4. Conduction System Pacing Leads 
Medtronic commercially available CSP pacing leads are required. 
 
7.2 Labeling 
In all geographies, the CRT-D/CRT-P devices used in this study are market-released and will be labeled 
according to the approved CE-mark labeling. The devices will be considered investigational during the 
course of the study. 
 
Market-released components will be provided with the approved CE-mark labeling. 
 
In the US, investigational labeling requirements for the ECG Belt and Millar Connector Cable will include 
the following statements: 
 
“CAUTION – Investigational device. Limited by Federal Law (USA) to Investigational use". 
 
In EMEA, labeling for the ECG Belt will include the following statement (labeling will be in English unless 
otherwise required for local regulations): 
 
“Exclusively for Clinical Investigations.” 
 
7.3 Product Use 
The CSPOT system is comprised of the components identified in Table 5: CSPOT Research System 
Components. The system components have all been individually approved (with the exception of the 
ECG Belt and the Millar Connection Cable (US only)) for other human use applications. The unique 
aspects of the CSPOT system are introduced by the use of these existing elements in combination and 
coordination as described throughout this specification. Each of the existing elements have 
instructions for use related to their existing uses; as part of the CSPOT Research System, the 3830 

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lead will be implanted in a non-market approved location. The rationale for using the 3830 lead is that it 
is the only available lead with a published record of use in the intraseptal location. 
Components intended for use in the sterile field, including the leads, pressure catheter and lead 
cables/pocket clip are provided in sterile packaging, except for the Millar connection cable. The Millar 
connection cable may be re-sterilized/sterilized per its instructions for use or a sterile sleeve may be 
used. Reusable components that may be exposed to body fluids, including the ECG Belt amplifier, the 
ECG cables and the lead cables, can be cleaned per their individual instructions for use.  Disposable 
components of the system, including only the pressure sensor catheter and ECG electrode array have 
a shelf life of at least 2 years. 
7.4 Product Storage 
Any components of the CSPOT Research System that are received or kept at the study site must be 
stored in a secure location at the study site. It is the responsibility of the investigator to correctly 
handle, store, and track the investigational products maintained at the study site. Investigational 
products will be used only in the clinical study according to the CIP. 
The market released components of the CSPOT Research System are the responsibility of the 
investigator to correctly handle and store. 
7.5 Product Accountability 
The CSPOT system is comprised of both commercially market-released and investigational products. 
The market-released devices used in this study will be considered investigational once they are used 
with the CSPOT Research System.  Commercially available product supply will be managed in a manner 
consistent with other market-released products. 
For investigational products used during the study, Product Distribution/Accountability logs will be 
used for tracking of products during and after the study. The tracking method might vary but could use 
either an electronic or paper accountability logs provided by Medtronic. The logs must be updated 
when the investigational product is received, opened, implanted, explanted, disposed of or returned to 
Medtronic. In addition to tracking the date of events, the log tracks product information including, but 
not limited to, date, model/serial number/lot number and expiration date for received product, subject 
ID of implanted subject, date implanted/used, date explanted (if applicable), date returned to 
Medtronic and reason for return (if applicable), reason for and method of destruction/disposal for 
explanted components not returned to Medtronic (if applicable), and name of person responsible for 
return or destruction/disposal (if applicable). 
 
Medtronic will perform periodic reconciliation of investigational product to ensure traceability. 
 
If there are additional local requirements related to the CSPOT Research System beyond what is 
collected by Medtronic on the eCRF, this is the Investigator’s responsibility and should be recorded in 
the subject’s medical records, but will not be collected by Medtronic (e.g., national registration card 
number, identification code linked to names and contact information, log of all subjects enrolled in the 
study, lot or batch number). 

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7.6 Product Training Materials 
Investigator training on use and handling on the CSPOT system will be required prior to first enrollment 
at a particular site. Study training on the CSPOT system was based according to the risk assessment. 
7.7 Product Return 
All explanted, unused or malfunctioning devices (devices or leads or activators, etc.) should be returned 
to Medtronic for analysis when permissible by local laws and regulations. If the products are explanted 
but not returned, a justification will be reported on the appropriate case report forms or disposition 
logs. To receive a Returned Product Mailer Kit, please contact your local Medtronic field personnel. 
 
 
8. Study Site Requirements 
 
 
8.1 Investigator/Investigation Site Selection 
All investigators managing the subject’s health care 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-D/CRT-P devices. 
The role of the Principal Investigator is to implement and manage the day-to-day conduct of the clinical 
investigation as well as 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 
• 
Disclose potential conflicts of interest, including financial, that interfere with the conduct of 
the clinical investigation or interpretation of results 
• 
Be able to demonstrate that the proposed investigational study site: 
 
Has the required number of eligible subjects needed within the recruitment period 
 
Has one or more qualified investigators, a qualified investigational study site team 
and adequate facilities for the foreseen duration of the clinical investigation 
 
Study site personnel training will be completed and documented prior to participation in this study. 
 
 
8.2 Study Site Activation 
During the activation process (prior to subject enrollment), Medtronic will train study site personnel on 
the clinical investigation plan, on relevant standards and regulations, informed consent, and on data 
collection and reporting tools. If new members join the study site team, they will receive training on the 
applicable study requirements relevant to their role before contributing to the study. 
Prior to performing study related activities, all regulatory requirements shall be fulfilled, including, but 
not limited to the following: 

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• 
EC approval (and voting list, as required by local law) of the current version of the CIP and IC 
• 
Regulatory Authority approval or notification (as required per local law) 
• 
Fully executed CTA; Medtronic contracts with participating institutions/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 
• 
Financial disclosure 
• 
CV of investigators and key members of the investigation study site team (as required). The 
signature on the CV must be dated within 3 years prior to the date of activation of the study 
site 
• 
Documentation of Delegated Tasks 
• 
Documentation of Site Technical Support 
• 
Documentation of study training 
• 
Additional requirements imposed by local regulations, the EC and RA shall be followed, if 
appropriate 
 
In addition, all participating study site staff must be trained on the current version of the CIP as well as 
on the applicable study requirements depending on their role and must be delegated by the principal 
investigator to perform study related activities. 
Medtronic will provide each study site with documentation of study site/investigator readiness; this 
letter must be received prior to performing study related activities. 
8.3 Role of the Sponsor Representatives 
Sponsor representatives may provide support at the study site 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 for acute study protocol and 6 months follow up visit under the 
supervision of a study investigator, but no data entry, shall be performed by Medtronic 
personnel or their representatives at study sites 
• 
Support study investigators in performing the study implant procedure 
• 
Monitoring and auditing activities 
 
In addition, for this study, sponsor representatives will be authorized to perform the following 
significant trial related duties: 
• 
Support data collection and performing the CSPOT protocol during the acute and during 
the 6-month chronic phase study follow up visit. 
• 
Support data collection during the implant procedure 

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9. Selection of Subjects 
 
 
9.1 Study Population 
The target population for the CSPOT study will include subjects who are indicated to receive a 
Medtronic CRT-D or CRT-P based on market approved indications. 
9.2 Subject Enrollment 
Ethics Board/IRB and Medtronic approval of this Clinical Investigation Plan, the informed consent form 
and any other applicable documents must be obtained prior to enrolling subjects in the study. 
Medtronic will provide each study site with documentation of study site/investigator readiness; this 
letter must be received prior to subject enrollment. 
When a patient and the Principal Investigator or authorized designee, as required, have personally 
signed and dated the informed consent form, the patient is considered a subject enrolled in the study. 
Subjects must provide informed consent before any study related procedures occur. The date the 
subject signed the informed consent form and data protection authorization as required by local law 
must be documented in the subject’s medical records. 
Subjects will be screened to ensure they meet all the inclusion and none of the exclusion criteria prior 
to study enrollment. 
9.3 Inclusion Criteria 
• 
Patient is willing and able to provide written informed consent 
• 
Subject is at least 18 years of age 
• 
Patient is willing and able to comply with the protocol, including follow-up visits 
• 
The patient’s medical records must be accessible by the enrolling site over the follow-up 
period 
• 
Standard CRT-D or CRT-P indications, with a preference for IVCD and non-LBBB patients, 
where LBBB is defined according to Strauss criteria. 
• 
De-novo CRT implant, including upgrade from pacemaker or ICD 
 
 
9.4 Exclusion Criteria 
• 
Subject has persistent or permanent AF (Atrial Fibrillation)/AFL (Atrial Flutter) 
• 
Subject has 2nd or 3rd degree AV (Atrioventricular) Block 
• 
Subject has RBBB with no additional conduction block 
• 
Subject has intrinsic (non-paced) QRS width less than or equal to 120 ms 
• 
Subject experienced MI within 40 days prior to enrollment 
• 
Subject underwent valve surgery, within 90 days prior to enrollment 
• 
Subject is post heart transplantation or is actively listed on the transplantation list 

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• 
Subject is implanted with a LV assist device 
• 
Subject has severe renal disease 
• 
Subject is on continuous or uninterrupted infusion (inotropic) therapy for heart failure 
• 
Subject has severe aortic stenosis (with a valve area of <1.0 cm or significant valve disease 
expected to be operated within study period) 
• 
Subject has severe aortic calcification or severe peripheral arterial disease 
• 
Subject has complex or repaired congenital heart disease 
• 
Subject has mechanical heart valve 
• 
Pregnant or breastfeeding woman (pregnancy test required for woman of child-bearing 
potential and who are not on a reliable form of birth regulation method or abstinence) 
• 
Subject is enrolled in another study that could confound the results of this study without 
documented pre-approval from Medtronic study manager 
 
 
10. 
Study Procedures 
 
 
10.1 Schedule of Events and Data Collection 
A patient will be considered enrolled in the study once they sign and date the Informed Consent. 
Subjects will complete an in-office visit at 6 months. The requirements for data collection and study 
procedures by visit are summarized in Table 6 below. 
 
Table 6: Data collection and study procedure requirements 
 
 
STUDY PROCEDURE 
Baseline 
(occur within 30 
days prior to 
enrollment) 
Implant 
(occur within 30 
days after 
enrollment) 
6 month follow 
up and Study 
Exit 
Patient Informed Consent 
X 
Inclusion/Exclusion Assessment 
X 
Demographics 
X 
Medical History 
X 
Physical Exam 
X 
X 
Medication Assessment 
X 
X 
Baseline 12-Lead ECG (within 60 days prior to enrollment/consent) 
X 
Baseline Echocardiography including LVEF and LVESV (within 60 days prior 
to enrollment/consent) 
X 
NYHA 
X 
X 
ECG Belt 
X 

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Lead Placement 
X 
CSPOT Research System Protocol 
X 
Insertion procedure information 
X 
Fluoroscopic Images of final LBBP lead placement 
X 
Patient Global Assessment 
X 
6 Month Echocardiography including LVEF and LVESV (within 30 days prior to 
visit) 
X 
6 Month 12-Lead ECG (within 30 days prior to visit) 
X 
Final device programming 
X 
X 
Initial and Final Device Interrogation (with either initial or final interrogate 
ALL) and collect a .pdd file 
X 
X 
Adverse Events 
As they occur 
Hospitalizations 
Death 
Device Deficiency 
System Modification 
Study Deviations 
 
10.2 Prior and Concomitant Medications/Therapies 
There are no medication/therapy restrictions in the study unless they are investigational and may 
confound the study results, in which case, prior approval would be needed from Medtronic. Medications 
will be collected at baseline and at 6-month follow up. 
10.3 Subject Consent 
The ICF is defined as a legally effective documented confirmation of a subject’s voluntary agreement to 
participate in a particular clinical study after information has been given to the subject on all aspects of 
the clinical study that are relevant to the subject’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 that has been approved by the study site’s 
Institutional Review Board/Ethics Committee (IRB/EC) and signed and dated by the subject. 
Investigators shall consider all subjects who meet eligibility requirements for study participation to 
avoid any bias in the subject population.  Prior to enrolling subjects, approval of the CIP, ICF, and any 
other written study information to be provided to the subjects must have been obtained from each 
site’s IRB/EC.  The document(s) must be controlled (i.e. versioned and dated) to ensure it is clear which 
version(s) were approved by the IRB/EC.  Any adaptation of the sample ICF must be reviewed and 
approved by Medtronic and the IRB/EC reviewing the application prior to enrolling the subject. 
The investigator must notify the subject of any significant new findings about the study that become 
available during 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. 

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Prior to initiation of any study-specific procedures, informed consent must be obtained from the 
subject. Likewise, privacy or health information protection regulation may require subjects to sign 
additional forms to authorize sites to submit subject information to the study sponsor.  The informed 
consent process must be conducted by the principal investigator or his/her authorized designee, and 
the ICF and Authorization to Use and Disclose Personal Health Information/Research 
Authorization/other privacy language as required by law must be given to the subject in a language 
he/she is able to read and understand.  The process of obtaining 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 site personnel.  The informed consent process shall not waive or appear to 
waive subject’s legal rights.  The language used shall be as non-technical as possible and the impartial 
witness, where applicable. 
The subject must have ample time and opportunity to read and understand the ICF, to inquire about 
details of the study, and to decide whether to participate in the clinical study. All questions about the 
study should be answered to the satisfaction of the subject. 
When the subject decides to participate in the clinical study, the ICF must be signed and personally 
dated by the subject acknowledging that their participation is voluntary and signed and personally 
dated by the 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, signed and dated as required by law, must be provided to the 
subject. 
If informed consent 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. 
In the event the subject cannot read and/or write, the IC process shall be obtained through a supervised 
oral process.  In this situation, an independent witness must be present throughout the                  
informed consent process.  The written informed consent form and any other information shall be read 
aloud and explained to the prospective subject. The witness signs and personally dates the IC attesting 
that the information was accurately explained and that informed consent was freely given. Whenever 
possible, the subject shall sign and personally date the informed consent form. 
The original of the signed IC must be filed in the hospital/clinical chart and/or with the subject’s study 
documents. 
Detailed documentation of the consent process must be recorded in the subject’s case history. The 
ICF should document a supervised oral process was used for communication with the prospective 
subject and the specific means by which the prospective subject communicated agreement to 
participate in the study. 

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The ICF and Authorization to Use and Disclose Personal Health information/Research 
Authorization/other privacy language as required by law must be available for monitoring and auditing. 
Any Medtronic Field personnel who support the CRT-D/CRT-P implant procedure must be able to 
review the subject’s original signed and dated ICF and verify its completeness prior to proceeding with 
the insertion. In the event the Medtronic Field personnel identify informed consent as being 
incomplete, the study procedure will not be allowed to occur until the consent of the subject can be 
adequately and appropriately obtained. 
Consistent with the DoH, vulnerable adults (i.e. those subjects mentally incapable of giving consent)  
are excluded from this protocol.  Any subjects with mental incompetence (e.g., Alzheimer’s, dementia, 
psychiatric disorders, developmental disorders) should be assessed for vulnerable status. If the IC is 
signed by an individual other than the subject, the monitor may discuss whether the Investigator 
believes the subject meets the definition of a vulnerable adult. This protocol defines vulnerable adult as 
those subjects 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: 
“individuals who are unable to fully understand all aspects of the investigation that are relevant to the 
decision to participate, or who could be manipulated or unduly influenced as a result of a compromised 
position, expectation of benefits or fear of a retaliatory response. 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 IC. Other vulnerable subjects could 
include, for example, members of a group with a hierarchical structure such as university students, 
subordinate hospital and laboratory personnel, employees of the sponsor, members of the armed 
forces, and persons kept in detention. 
10.4 Enrollment 
A subject is considered enrolled when the consent process has been finalized. The date the subject 
signed the IC and Data Protection Authorization, as required by law, must be documented in the 
subject’s medical records. A log of all subjects enrolled in the study should be maintained. Enrollment 
can be a stand-alone visit or can occur on the same day as the baseline visit. Once consent is obtained, 
report adverse events/deaths, study deviations and subject exits as they occur. 
10.5 Baseline 
Following subject enrollment, a baseline visit will be performed within 30 days. The baseline visit can be 
a standalone visit or occur on the same day as enrollment.  The following procedures/data collection 
will be conducted during the baseline visit: 
• 
Inclusion/exclusion criteria assessment 
• 
Demographics 
• 
Medical History 
• 
Physical Exam 

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• 
Medication Assessment 
• 
Baseline 12-Lead ECG (within 60 days prior to enrollment) 
• 
Baseline Echocardiography including LVEF and LVESV (within 60 days prior to enrollment) 
• 
NYHA classification 
• 
Adverse events (as applicable) 
• 
Hospitalizations (as applicable) 
• 
Death (as applicable) 
• 
Study Deviations (as applicable) 
 
10.6 CRT-D/CRT-P Implant 
Following subject baseline, implant procedure of the CRT-D/CRT-P device will be performed within 30 
days from subject enrollment. The implant procedure visit can be a standalone visit or occur on the 
same day as baseline. The following procedures/data collection will be conducted during the implant 
visit: 
• 
Insertion procedure information 
• 
ECG Belt application and data collection 
• 
Lead Placement 
• 
CSPOT Research System protocol 
• 
CSPOT Chronic Final Device programming 
• 
Initial and Final Device Interrogation (with either the initial or final being an interrogate ALL) and 
collection of .pdd file 
• 
Fluoroscopic Images of final LBBP lead placement in RAO 30-45 degrees, LAO 30-45 degrees, 
and AP 
• 
Adverse events (if applicable) 
• 
Hospitalizations (if applicable) 
• 
Death (if applicable) 
• 
Device Deficiency (if applicable) 
• 
System Modifications (if applicable) 
• 
Study Deviations (if applicable) 
 
10.6.1 CSPOT Acute Pacing Protocol 
The CSPOT Acute Pacing Protocol and Medtronic CRT-D/CRT-P implant procedure must occur within 
30 days of enrollment and will be performed in accordance with the Medtronic respective CRT-D/CRT- 
P implant instructions. The CSPOT pacing protocol should take place prior to the implant of the 
Medtronic CRT-D/CRT-P.  During the CSPOT pacing protocol, two different sets of electrodes will be 
placed on the patient’s chest: 1) a 12-lead surface ECG and 2) a multi-electrode ECG-belt. 

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Pacing leads (and defibrillation lead for CRT-D) will then be positioned as described in the CSPOT User 
Manual. Finally, a Millar pressure catheter will be introduced via the femoral artery retrograde across 
the aortic valve into the LV for hemodynamic pressure monitoring. 
 
The different pacing configurations are depicted below and include univentricular (LVcs) pacing (CRT-P 
implants only), LVcs and RV pacing (CRT-D implants only) , univentricular CSP (LBBP), and conduction 
system pacing optimized therapy (CSPOT) which is dual LV pacing of best LVcs and CSP. Different 
atrioventricular (AV) and intra-ventricular VV intervals will be evaluated. See figure 3 below for an 
overview. 
 
Figure 3: Pacing Configurations 
 
 
 
 
 
 
 
 
 
 

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• 
 
 
 
• 
 
 
 
 
 
• 
 
 
 
 
 
 
 
• 
 
 
 
 
 
 
 
 
 
• 
 
 
 
 
 
 
 
 
 
• 
 
 
 
 
 
 
 
 
• 
 
 
 
 
 
 

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10.6.2 CSPOT Chronic Final Device Programming 
After the acute pacing protocol, the patient is implanted with a CRT-P or CRT-D device, connected to 
the leads that were positioned during the acute study.  For CRT-D patients, the pin for RV tip and ring 
will be capped.  After the CRT device is implanted and the pocket is closed per standard of care, the 
device will be programmed to the CSPOT configuration that indicated the best optimization according 
to ECG Belt and/or physician discretion. This includes the SAV, PAV, and VV delay. The best LVcs 
electrode that was used during the acute testing will also be used for chronic programming unless 
phrenic nerve stimulation, lead dislodgement or high capture threshold occur.  If the patient is not 
programmed to the CSPOT configuration, the subject must be exited from the study. 
 
The chronic device programming includes: 
 
Table 7: Device programming during chronic follow up. 
 
Feature 
Programmed Value 
AdaptivCRT 
Nonadaptive CRT 
V-V pace delay 
According to best result from ECG Belt during 
acute study and/or physician discretion 
Paced AV 
According to best result from ECG Belt during 
acute study and/or physician discretion 
Sensed AV 
Programmed to a value between (Paced AV – 
30ms) and (Paced AV – 100ms), according to 
physician discretion. 
LV pacing vector 
Select the best LV cathode according to ECG 
Belt and/or physician discretion.  Select 
anode according to physician discretion.   
Multiple Point Pacing (MPP) 
Off 
RV Pace Polarity 
Bipolar 

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Rate Adaptive AV 
On 
Pace Amplitudes and Pulse Widths 
Automatic capture management 
recommended 
All other device parameters 
According to physician discretion 
 
 
 
10.7 Scheduled Follow-up Visits 
A scheduled visit will occur at 6 months post implant.  Should a subject miss the visit or the visit fall 
outside the pre-specified window, a study deviation must be reported. A late visit is preferred over a 
missed visit but must be accompanied by a deviation.  The table below indicates the follow up visit 
windows. 
 
Table 8: Windows for follow-up visits 
 
Visit 
Window (days post enrollment) 
Open 
Target 
Close 
Baseline 
0 
15 
30 
Visit 
Window (days post enrollment) 
Open 
Target 
Close 
Implant 
0 
15 
30 
Visit 
Window (days post implant) 
Open 
Target 
Close 
6-Month Follow Up 
150 
180 
210 

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10.7.1 6-Month In-Office Follow Up Visit 
An in-office follow-up visit will be completed at 6 months post device insertion to collect chronic data 
from the CSPOT system. 
 
The following information is required to be collected at the 6-Month scheduled follow-up visit: 
• 
Physical Exam 
• 
Medications Assessment 
• 
NYHA Classification 
• 
Patient Global Assessment 
• 
6-Month 12 lead ECG (within 30 days prior to visit date) 
• 
6-Month Echocardiography including LVEF and LVESV (within 30 days prior to visit date) 
• 
Final Device Programming 
• 
Initial and Final Device Interrogation (with either the initial or final being an interrogate ALL) and 
collection of .pdd file 
• 
Adverse events (if applicable) 
• 
Hospitalizations (if applicable) 
• 
Device Deficiencies (if applicable) 
• 
Study Deviations (if applicable) 
• 
System Modifications (if applicable) 
• 
Death (if applicable) 
 
10.7.1.1 Final Device Programming 
After the 6-month follow up visit procedures are completed, the subject’s device will be programmed 
per physician discretion. A final device interrogation and collection of .pdd file is required to capture 
final device settings. 
 
10.7.2 Study Exit 
At the completion of the 6-month follow-up visit, subjects will be exited from the study. The 6-month 
follow-up visit and exit visit should be combined and both a 6-month follow-up CRF and a Study Exit 
CRF need to be completed. 
Prior to exiting a subject from the study, it is recommended to follow the subject until all ongoing 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.  All data available through the time of the subject’s exit will be 
used for analysis. Subjects who are exited from the study prior to the 6 months visit will not be replaced 
with another enrolled subject. 
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: 
• 
Study completion or termination 

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• 
Subject lost to follow-up 
• 
CRT-D/CRT-P device explanted and not replaced 
• 
Implant attempt, however, no CRT-D/CRT-P was implanted 
• 
Subject has an invasive system modification that has intent to change the pacing 
behavior from the acute system configuration settings 
• 
The following occurs during the lead positioning in the acute protocol testing: 
 
Unable to place the LBBP lead 
 
Unable to place the LV lead through the CS 
 
Subject has a sustained sinus rate > 110 BPM 
 
Subject has sustained AV block, AF, or SVT 
• 
Subject death 
• 
Subject did not meet inclusion/exclusion criteria 
• 
Subject was not implanted with a Medtronic CRT-D/CRT-D device 
• 
Subject did not provide consent or data use protection authorization 
• 
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/procedure is to be collected/performed at study exit: 
• 
Date of Exit 
• 
Reason for Exit 
• 
Initial and Final Device Interrogation (with either the initial or final being an interrogate 
ALL) and collection of .pdd file 
• 
Adverse Event Collection 
• 
Device deficiencies 
• 
Study deviations 
If discontinuation is because of safety or lack of effectiveness, the subject may be asked to be followed 
for collecting safety data outside the clinical investigation. 
10.7.3 Lost to Follow-up 
A subject is considered to be lost to follow-up if at least two attempts to contact the subject are 
unsuccessful. The method of attempt (e.g., one letter and one phone record, or two letters) must be 
documented in the subject’s medical record. In addition, regulation set forth by the governing EC must 
be followed If allowed per local regulations, a person identified by the subject is informed of the 
possibility to be contacted by the principal investigator regarding how to reach the subject and the 

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subject’s health status and a civil register may be contacted by the principal investigator to inquire 
about the subject’s whereabouts 
10.7.4 Subject Chooses to Exit (i.e., Revokes Consent) 
A subject can withdraw from the study at any time. If the subject wishes to exit from the study (i.e. the 
subject revokes consent), the study site is required to document the reason for exit on the Exit CRF. In 
addition, study sites shall follow the regulations set forth by the governing EC. Permission may be 
requested to follow up with the subject outside of the study due to withdrawal based on problems 
related to the investigational feature safety or performance. If possible, the following data should be 
collected prior to subject withdrawal: 
• 
Reason for exit if patient is willing to share 
• 
All ongoing AEs are resolved or unresolved with no further actions planned 
If no physical visit is associated with the withdrawal or withdrawal occurs prior to baseline visit, none 
of the procedures listed are required. 
10.7.5 Investigator Withdraws Subject 
No subject should be withdrawn by investigators unless compelling medical justification is present. It is 
recommended investigators discuss any withdrawals with the study team prior to withdrawing 
subjects. If an Investigator Withdrawal is necessary, the following data should be collected prior to 
subject withdrawal if possible: 
• 
Reason for investigator withdrawal from the study 
• 
All ongoing AEs are resolved or unresolved with no further actions planned 
In the event of subject relocation, it is recommended to contact the study team to attempt to 
transfer the subject to another investigational site and retain the subject in the study. 
10.8 Device Interrogation 
For any programming changes or device interrogations occurring at the study site, an initial and final 
device interrogation .pdd file (with either the initial or final being an “Interrogate ALL”) must be 
obtained and saved in a digital format. Store the original file at the study site and send a copy to 
Medtronic.  It is recommended that data are not cleared during any interrogation. 
10.9 System Modification 
A system modification will be reported via a System Modification CRF in the event the initially implanted 
device or leads require non-invasive modification (repositioning of leads, device battery change out) 
and the intent is to continue the same pacing behavior as the original system was configured. 
If the implanted device or leads require an invasive modification (e.g., device or lead explant, device or 
lead replacement/repositioning with intent to change pacing behavior from original system) the System 
Modification CRFwillbecompletedandthesubjectwillbeexitedafterallsystemand/orprocedure related AEs 
havebeen resolved orremain unresolved withnofurtheraction planned. 
In the event of a non-invasive system modification, the follow-up schedule for the subject will remain 
unchanged. 

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For any system modification the following activities are required: 
• 
Complete the System Modification CRF regarding details of the system modification 
procedure 
• 
Device interrogation on the system modification if at all possible: 
 
if device is explanted: Interrogate ALL and collect .pdd file 
 
if new device implanted: Interrogate ALL and collect .pdd file 
 
if lead revision: Interrogate (with either initial or final being an interrogate ALL) and 
collect .pdd file 
• 
Adverse Event Collection if applicable 
• 
Device Deficiencies if applicable 
• 
Study Deviations if applicable 
 
All explanted product should be returned to Medtronic for analysis when permissible by local laws and 
regulations. 
10.10 Medication Assessment 
The name, dose, frequency and route of all medications will be collected at baseline and at the 6 month 
follow up visit. Changes to medications will be captured on the Medication Log eCRF. 
There are no medications that are required for this study although some medications may be 
administered in treating specific conditions at the discretion of the physician. The only medications 
that are excluded from use during this study are investigational. 
 
10.11 Assessment of Safety 
AE information is collected in this study. See Section 12 for further information on the collection of AEs 
and safety information. 
All AEs will be collected throughout the duration of a subject’s participation in the study, beginning at 
the time of informed consent. Additionally, any device deficiencies related to the Medtronic CRT- 
D/CRT-P will be collected. Adverse events and device deficiencies will be reported to Medtronic via 
completion of eCRFs. See section 12 for additional details. 
10.12 Recording Data 
Subject data will be collected on electronic case report forms (eCRFs) via an electronic data capture 
(EDC) system. The investigator must ensure accuracy, completeness and timeliness of the data 
reported in the eCRFs. Only authorized persons can complete and sign e-CRFs, as specified on the 
Delegated Tasks List included in the Investigator Site File. 
Procedures in the CIP require source documentation. Source documentation is defined as the first time 
data appear, and may include original documents, data, and records (e.g., hospital records, clinical and 

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office charts, procedure reports, laboratory notes, memoranda, subjects’ diaries or evaluation 
checklists, pharmacy dispensing records, recorded data from automated instruments, copies or 
transcriptions certified after verification as being accurate copies, microfiches, photographic 
negatives, microfilm or magnetic media, X-rays, subject files, device data and records kept at the 
pharmacy, at the laboratories and at medico-technical departments involved in the study). 
In general, eCRFs (or paper copies) may not serve as source documents. Source documentation for 
data elements not routinely captured in medical records may vary from study site to study site; the 
study site may use source document worksheets if identified as source documents. 
The investigator must ensure the availability of source documents from which the information on the 
eCRFs was derived. The type and location of source documents should be documented. Where 
printouts of electronic medical records, are provided as source documents, or where copies of source 
documents are retained as source documents, those should be certified. Certification must contain (1) 
the signature of the individual making the copy, (2) the date the copy was made and (3) a statement 
attesting to the accuracy and completeness of the copy. 
The source documents must be made available for monitoring or auditing by Medtronic’s 
representative or representatives of the competent authorities and other applicable regulatory 
agencies. 
The CRF may be considered source for the following data collection elements: 
• 
Enrollment Notification 
 
Study site assigned subject reference 
• 
Baseline 
 
Administrative information 
• 
AE eCRF 
 
Date study site became aware of event 
 
Relatedness of adverse event 
• 
DD eCRF 
 
Date study site became aware of event 
• 
Subject Death 
 
Date study site became aware of death 
 
Relatedness of death 
 
System explant information 
• 
System Modification 
 
Justification for explanted product not being returned to Medtronic 
• 
Deviations 
 
Reason for deviation 

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Device data from transmissions will be uploaded to secure servers. Media/USB data collected at office 
visits will be sent to Medtronic.  Upon receipt, device data will be maintained with databases and 
retrieved for analysis and reporting. 
Refer to section 16.2 for additional detail regarding data management for the study. 
 
10.13 Deviation Handling 
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. If an infringement remains unresolved, multiple 
deviations need not be completed. The use of waivers is prohibited for deviating from the CIP. 
Prior approval by Medtronic is expected in situations where the investigator anticipates, contemplates, 
or makes a conscious decision to deviate.  Prior approval is not required when a deviation is necessary 
to protect the safety, right 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). 
For medically justifiable conditions which preempt a subject’s ability to complete a study-required 
procedure, it may be permitted to report only one deviation which will apply to all visits going forward. 
This may also apply for other unforeseen situations (e.g. the subject permanently refuses to complete 
a study required procedure and the data will not contribute to the primary end point analysis). 
However, prior approval from Medtronic is required for such situations. 
All study deviations must be reported on the study deviation e-CRF regardless of whether medically 
justifiable, pre-approved by Medtronic, an inadvertent occurrence, or taken to protect the subject in an 
emergency. The deviation description and reason for deviation must be recorded. Multiple deviations 
of the same type at the same visit may be reported on one e-CRF. 
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 IRB/EC as 
well as Medtronic within five (5) working days.  Reporting of all other study deviations must comply with 
IRB/EC policies and/or local laws and/or regulatory agency requirements and must be reported to 
Medtronic as soon as possible upon the site becoming aware of the deviation. Refer to 16.8 for 
geography specific deviation reporting requirements and timeframes for reporting to Medtronic 
and/or regulatory bodies. 
Medtronic is responsible for analyzing deviations, assessing their significance, and identifying any 
additional corrective and/or preventive actions (e.g. amend the Clinical Investigation Plan, conduct 
additional training, 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 

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investigator’s participation in the study.  Medtronic will provide site-specific reports to investigators 
summarizing information on deviations that occurred at the investigational site on a periodic basis. 
 
 
11. 
Risks and Benefits 
 
 
11.1 Potential Risks 
Medtronic follows rigorous Quality Assurance and Control procedures throughout the life of a product, 
from the business analysis phase through development, market release, and post-market surveillance. 
The risk analysis process for the CSPOT Research System is being performed in accordance with ISO 
14971:2019 and ensures that the level of risk is acceptable prior to starting the study. In Europe a 
summary of the risk analysis and risk assessment will be listed in the IB. 
The potential risks to a subject participating in this study are believed to be somewhat higher than 
those encountered during standard CRT (CRT-P and/or CRT-D) implantation. This is due to 1) the 
prolonged duration of the complete procedure, 2) the insertion of the Millar catheter in the left 
ventricle, and 3) in CRT-D devices, the addition of the CSP lead for LBBP. The potential adverse events 
are outlined below: 
 
• 
Allergic reaction 
• 
AV fistula 
• 
Bradyarrhythmia 
• 
Cardiac arrest 
• 
Cardiac inflammation 
• 
Cardiac perforation 
• 
Cardiac tamponade 
• 
Cardiac valve damage 
• 
Discomfort 
• 
Dizziness 
• 
Dyspnea 
• 
Embolism 
• 
Fever 
• 
Groin site injury 
• 
Hematoma 
• 
Hemorrhage 
• 
Hiccups 
• 
Hospitalization 
• 
Infection 
• 
Lethargy 
• 
Mental anguish 
• 
Palpitations 
• 
Pneumothorax 
• 
Physical injury 

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• 
Return of cardiac symptoms 
• 
Skeletal muscle sensation or twitching 
• 
Skin disorders 
• 
SVC tear 
• 
Syncope 
• 
Tachyarrhythmia 
• 
Threshold elevation 
• 
Tissue trauma 
• 
Vessel perforation 
 
Kidney dysfunction could be another risk because of increased use of contrast fluid used during the 
total study protocol. 
Bleeding and bruising may be more likely to occur with the administration of blood-thinning 
medications (heparin) to minimize the risk of blood clot formation during the procedure. 
Procedure prolongation will not only increase duration of the anesthesia but also the risk of infection. 
The protocol procedures may take up to 90 minutes longer than the standard CRT procedure time 
which includes up to 10 minutes of fluoroscopy exposure. 
Placement of the 3830 lead to pace the left bundle branch could result in: temporary or permanent 
right bundle branch block, tricuspid valve damage, or perforation of the ventricular septum. 
 
Additional potential risks associated with the CSPOT Research System to a subject participating in this 
study are: 
• 
The CSPOT system is investigational and may be no more effective or less effective than a 
commercially available CRT system. 
• 
The CSPOT system may recommend values that are different than anticipated due to 
unknown circumstances or medical conditions. 
• 
There may be other discomforts and risks related to the CRT-D/CRT-P, Millar Catheter, 
ECG Belt and/or this study that are not foreseen at this time. 
• 
The lead implant configurations for this study are considered investigational and have not 
been studied for MRI use. Therefore, the MRI conditional labeling will not apply for these 
patients. 
 
 
11.2 Risk Minimization 
The potential risks associated with the CSPOT Research System were identified and have been 
mitigated; see Table 9 below. Any potential risks associated with this study are further minimized by 
selecting qualified investigators and training study personnel on the CIP. 
In addition, investigators will be actively involved in the implantation and follow-up of the subjects 
implanted with the CRT-D/CRT-P device. 

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Risks will be minimized by careful assessment of each subject prior to, during, and after implant of the 
CRT-D/CRT-P device. Prior to implant, it is recommended subjects undergo a complete physical 
evaluation. 
Medtronic has further minimized the possibility of risks by performing required laboratory and pre- 
clinical testing prior to the CSPOT study, implementing quality control measures into production 
processes, providing guidelines for subject selection and evaluation, and providing adequate 
instructions and labeling. 
After implantation, subjects in the CSPOT study will be followed for 6 months to monitor the condition 
of the implanted system. At each protocol required follow-up, the investigator must interrogate the 
CRT-D/CRT-P to verify appropriate function and to evaluate pacing and sensing characteristics and to 
assess any adverse events. 
 
Table 9: Potential risks and risk minimization 
 
Potential risk 
Risk Minimization 
Precursor to infection 
Associated AEs: Infection, Cardiac 
inflammation, Discomfort, Fever 
• CSPOT research system design verification ensuring intended 
use in the sterile field - including the leads, Millar LV pressure 
catheter, and lead cables/pocket clip are all provided in sterile 
packaging 
• CSPOT research system design verification ensuring reusable 
components can be re-sterilized – including IFU instructions 
on re-sterilization (if applicable) 
• Instruction provided in IFU for implant procedure; specifically, 
for the placement of leads, set-up of Millar LV pressure 
catheter, and appropriate pacing protocol/configuration 
Precursor to acute tissue/vascular 
trauma 
Associated AEs: Cardiac perforation, 
Cardiac tamponade, Cardiac valve 
damage, Discomfort, SVC tear, 
Hematoma, Embolism, Hemorrhage, AV 
fistula, Cardiac inflammation, Tissue 
trauma, Vessel perforation 
• CSPOT research system design verification ensuring 
compliance to EN 60601-1:2006/A1:2013 
• Instruction provided in IFU for implant procedure; specifically, 
for the placement of leads and set-up of Millar LV pressure 
catheter 

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Potential risk 
Risk Minimization 
Missing/misleading information causing 
insufficient/inappropriate medical 
intervention 
Associated AEs: Cardiac arrest, 
Lethargy, Dizziness, Return of cardiac 
symptoms, Syncope, Threshold 
elevation, Skeletal muscle sensation or 
twitching, Discomfort, Dyspnea, Mental 
anguish, Hiccups, Infection, 
Hospitalization, Hematoma 
• CSPOT research system design verification ensuring 
dependability (instantaneous reliability required for implant) 
and shelf life 
• Instruction provided in IFU to verify that components are not 
used beyond prescribed shelf life 
Bio-incompatibility 
Associated AEs: Allergic reaction, Skin 
disorders 
• CSPOT research system design verification ensuring no 
bioincompatible materials are used 
Arrhythmia induction (pacing during 
vulnerable period, proarrhythmic 
pauses, electrical/mechanical stimulus) 
Associated AEs: Cardiac arrest, 
Lethargy, Dizziness, Palpitations, 
Syncope, Tachyarrhythmia, 
Bradyarrhythmia 
• CSPOT research system design verification ensuring electrical 
immunity to interference within its environment of use 
• Instruction provided in IFU for implant procedure; specifically, 
for the placement of leads, set-up of Millar LV pressure 
catheter, and appropriate pacing protocol/configuration 
Inadequate tachyarrhythmia therapy 
Associated AEs: Cardiac arrest, 
Lethargy, Dizziness, Palpitations, Return 
of cardiac symptoms, Syncope 
• CSPOT research system design verification ensuring electrical 
immunity to interference within its environment of use 
Extracardiac stimulation 
Associated AEs: Dyspnea, Hiccups, 
Skeletal muscle sensation or twitching, 
Discomfort, Mental anguish 
• CSPOT research system design verification ensuring electrical 
immunity to interference within its environment of use 
• Instruction provided in IFU for implant procedure; specifically, 
for appropriate pacing protocol/configuration 
User/patient exposure to physical injury 
Associated AEs: Cardiac arrest, Physical 
injury 
• Instruction provided in IFU for implant procedure; specifically, 
for to include ways to secure components to minimize risk to 
the user, and disclosure of thermal risks and warnings for the 
isolation transformer 

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Potential risk 
Risk Minimization 
Product integrity/functionality failure 
from environment influences 
Associated AEs: Many harm outcomes 
are possible. Cardiac arrest is chosen as 
the worst-case outcome in terms of 
safety risk (severity*occurrence). 
• CSPOT research system design verification ensuring electrical 
immunity to interference within its environment of use 
 
11.3 Potential Benefits 
The CSPOT Research System may offer no direct personal benefit to individual subjects. The potential 
benefits of using the CSPOT research system include receiving a patient specific configuration to 
optimize pacing.  The information gained from this study could result in the improved management of 
other optimized pacing therapies. 
 
 
11.4 Risk-Benefit Rationale 
The result of the analysis for risks, along with the mitigation of the risks as described above, led to 
consider that the potential benefits that may derive from an optimized and customized CRT therapy 
outweigh the amount of risk. Overall residual risk of participating in the CSPOT study is considered low 
and acceptable. 
 
 
12. 
Adverse Events and Device Deficiencies 
 
 
12.1 Adverse Events 
AE definitions are provided in Table 10. To comply with ISO 14155:2020, all adverse events (AEs) will be 
collected throughout the duration of a subject’s participation in the study and reported per the study 
protocol. In addition, AEs impacting users or other persons, Non-subject Adverse Events will be 
collected. In all geographies, Unavoidable AEs, listed in Table 10, need not be reported unless the 
adverse event worsens or is present outside the stated timeframe post-implant. 
For AEs that require immediate reporting initial reporting may be done by phone, fax, or on the eCRF 
completing as much information as possible. The completed AE eCRF must be submitted to Medtronic 
as soon as possible. 
Any medication/treatment associated with the treatment of an AE must be reported. 
Subject deaths are also required to be reported. Refer to Section 12.6 for Subject Death collection and 
reporting requirements. 
12.2 Device Deficiency 
The DD (Device Deficiency) definition is provided in Table 10. To comply with ISO 14155:2020, DD 
information will be collected throughout the study and reported to Medtronic. Note that a DD that 
results in an AE to the subject should be captured as an AE only. 

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A DD that did not lead to an AE but could have led to a SADE (i.e., if suitable action had not been taken, if 
intervention had not been made, or if the circumstances had been less fortunate) requires immediate 
reporting. 
12.3 Processing Updates and Resolution 
For any changes in status of a previously reported adverse event or DD (i.e., change in actions taken, 
change in outcome, change in relatedness), information needs to be updated on, or added to the 
original AE or DD form. All 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 completion, all efforts should be made 
to continue following the subject until all AEs are resolved or unresolved with no further actions 
planned.  Additionally, if there are unresolved system or procedure related AEs at the time of study 
completion, all efforts should be made to collect additional information to have AEs resolved. Once the 
ongoing system or procedure AE(s) is/are resolved, the subject should be exited. If AEs are still ongoing 
at study completion after efforts have been made to resolve them, it should be noted on the AE CRF 
that the AE is unresolved at time of study exit. 
At the time of study exit, all collected adverse events that are unresolved must be reviewed and an 
update to the original AE must be reported. 
12.4 Definitions/Classifications 
Adverse event (AE) and device deficiency (DD) ISO 14155:2020 definitions are provided in Table 10 
below. Where the definition indicates “device”, it refers to any device used in the study. This might be 
the device under investigation, or any market released component of the system. Where the US and 
ISO terminology differs, the US term is listed first, followed by the ISO term. 
Table 10: Adverse Event and Device Deficiency Definitions 
 
General 
Adverse Event (AE) 
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 and whether anticipated or unanticipated. 
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 or comparators. 
(ISO 14155:2020, 3.2) 

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Adverse Device Effect (ADE) 
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. 
NOTE 3: this includes ‘comparator’ if the comparator is a 
medical device 
(ISO 14155:2020, 3.1) 
Device Deficiency (DD) 
Inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety or performance. 
NOTE 1: Device deficiencies include malfunctions, use 
errors and inadequate in the information supplied by the 
manufacturer including labeling. 
NOTE 2: This definition includes device deficiencies 
related to the investigational medical device or the 
comparator. 
(ISO 14155:2020, 3.19) 
Relatedness 
CRT-D/CRT-P Procedure Related 
An adverse event that occurs that is directly related to the 
insertion or modification of the CRT-P/CRT-D system. 
CRT-D/CRT-P System Related 
An adverse event that occurs that is directly related to the 
CRT-P/CRT-D system (including components like the 
CRTP/CRTD incision/insertion tools) 
CSPOT System Related 
An adverse event that results from the presence or 
performance of any component of the CSPOT system 
(including the Cardiotek, ECG Belt, and other system 
components) 
Cardiovascular Event 
An adverse event related to the heart and blood vessels or the 
circulation. 
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; 

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• 
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); 
• 
Harm 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. 
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 be 
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 
o 
the investigational device or 
procedures are applied to 
o 
the investigational 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); 

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 
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); 
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) 
Adverse event that led to any of the following: 
a) death, 
b) serious deterioration in the health of the subject, users 
or other persons as defined by one or more of the 
following: 
1. a life-threatening illness or injury, or 
2. a permanent impairment of a body structure or a 
body function, including chronic disease, 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) foetal distress, foetal death or a congenital abnormality 
or birth defect including physical or mental impairment 
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. 
(ISO 14155:2020, 3.45) 
Serious Adverse Device Effect (SADE) 
Adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event. 
(ISO 14155:2020, 3.44) 
Complication 
An adverse event that includes the following is 
considered a complication: 
• 
Results in death, 
• 
Involves any termination of 
significant device function, or 

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• 
Requires an invasive intervention 
Non-invasive (21 CFR 812): when applied to a 
diagnostic device or procedure, means one that does 
not by design or intention: 
• 
Penetrate or pierce the skin or mucous 
membranes of the body, the ocular cavity, or 
the urethra, or 
o 
Penetrate: to pass, extend, pierce, 
or diffuse into or through 
something; to enter by 
overcoming resistance; to gain 
entrance to 
o 
Pierce: to force a way into or through 
something 
• 
Enter the ear beyond the external auditory 
canal, the nose beyond the nares, the mouth 
beyond the pharynx, the anal canal beyond the 
rectum, or the vagina beyond the cervical os 
Note (FDA): Blood sampling that involves simple 
venipuncture is considered noninvasive, and the use of 
surplus samples of body fluids or tissues that are left over 
from samples taken for non- investigational purposes is 
also considered noninvasive. 
Observation 
Any Adverse Event that is not a complication. 
Note 1: Cardiovascular and Heart failure related AEs will be 
the only AEs requiring classification of either Complication 
or Observation by Sponsor and CEC. 
Unanticipated Adverse Device Effect (UADE) 
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): 
Serious adverse device effect which by its 
nature, incidence, severity or outcome has not 
been identified in the current version of the risk 
assessment 
NOTE 1: Anticipated serious adverse device effect 
(ASADE) is an effect which by its nature, incidence, 

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severity or outcome has been identified in the risk 
assessment. 
(ISO 14155:2020, 3.42) 
Serious Health Threat 
Signal from any adverse event or device 
deficiency that indicates an imminent risk of 
death or a serious deterioration in the health in 
subjects, users or other persons, and that 
requires prompt remedial action for other 
subjects, users or other persons 
NOTE 1: This would include events that are of 
significant and unexpected nature such that they 
become alarming as a potential serious health 
hazard or possibility of multiple deaths occurring 
at short intervals. 
(ISO 14155:2020, 3.46) 
Other 
Non-Subject Adverse Event (users or other persons) 
An Adverse Event or Serious Health Threat related to the 
investigational medical devices or comparators that 
impact users or other persons 
Unavoidable Adverse Event 
An Adverse Event inherent to a surgical procedure that is 
expected to occur in all subjects for a projected duration 
according to the Investigator’s opinion, including, but not 
limited to: 
Unavoidable adverse events are not reportable unless the AE 
worsens or is present outside the stated timeframe. 
Event Description 
Timeframe 
(hours) from 
the Surgical 
Procedure 
Anesthesia related nausea / vomiting 
24 
Low-grade fever (<100°F or 37.8°C) 
48 
Pocket site / Incisional pain 
72 
Mild to moderate bruising / ecchymosis 
168 
Sleep problems (insomnia) 
72 
Back pain related to laying on table 
72 
Shoulder pain/discomfort/stiffness 
related to  shoulder immobilization 
during procedure 
72 

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12.5 Reporting of 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 will be conducted in 
accordance with these procedures and regulations. 
Adverse Event and Device Deficiency data collection starts once the subject is consented and 
continues throughout the study, and updates are expected when there are changes in status of a 
previously reported adverse event including change in actions taken, change in outcome, or change in 
relatedness. If applicable, these AEs and DDs will be reported to other countries where studies are 
conducted with the same or a similar product. 
 
 
12.5.1 Adverse Event and Device Deficiency Collection 
12.5.1.1 Adverse Events 
 
Reporting of AEs to Medtronic will occur on an Adverse Event eCRF, including a description of the 
event, the diagnosis, the date of event onset, the date the site became aware of the event, the 
relatedness and seriousness of the event, diagnostic tests and procedures performed, actions taken as 
a result of the event, and outcome of the event. Each AE must be recorded on a separate AE eCRF. 
Subject deaths are also required to be reported and should be collected on an AE CRF with a Fatal 
outcome. Refer to section 12.6.1 for subject death collection and reporting requirements. In addition, 
AEs impacting users or other persons will be collected on a Non-subject Adverse Event eCRF. 
Documented pre-existing conditions are not considered AEs unless the nature or severity of the 
condition has worsened post implant. In all geographies, unavoidable adverse events, listed in Table 10, 
need not be reported unless the adverse event worsens or is present outside the stated timeframe. 
For any changes in status of a previously reported AE (i.e., change in actions taken, change in outcome, 
change in relatedness), an update to the original AE must be provided. All reported adverse events 
must be followed until the adverse event has been resolved, the subject exits the study or until study 
closure, whichever occurs first.  At the time of study exit, all collected AEs with an outcome of “not 
recovered/not resolved”, “recovering/resolving” or “unknown” must be reviewed and updates 
provided as applicable. 
 
12.5.1.2 Device Deficiencies 
Device deficiency (DD) information will be collected throughout the study and reported to Medtronic. 
Reporting of DDs to Medtronic will occur on a device deficiency eCRF. Note that DDs that result in an 
adverse device effect (ADE) to the subject should be captured on an AE eCRF only. Device deficiencies 

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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. 
12.5.2 Adverse Event and Device Deficiency Classification 
All reported AEs and DDs will be reviewed by a Medtronic representative. Adverse events will be 
classified according to the standard definitions as outlined in Table 11. 
Upon receipt of AE at Medtronic, a Medtronic representative will review the AE/DD for completeness 
and accuracy and when necessary will request clarification and/or additional information from the 
Investigator. Medtronic will utilize MedDRA to assign a term for each AE based on the information 
provided by the investigator. 
Regulatory reporting of AEs and DDs will be completed according to local regulatory requirements. 
Refer to Table 12 for a list of required investigator and Medtronic reporting requirements and 
timeframes. It is the responsibility of both to abide by any additional AE reporting requirements 
stipulated by the EC responsible for oversight of the study. 
Section 18.7 contains the FAL, which is a list of AEs related to harms observed in previous studies and 
may be experienced by subjects. This list may help to assist if an AE is unanticipated in nature. 
Anticipated adverse events and adverse device effects along with residual risk with the study product 
is identified in the risk analysis report, located in the IB. 
For emergency contact regarding a U(S)ADE, SAE and/or SADE, contact a study representative 
immediately (refer to the study contact list provided in the study site’s study documents 
binder/investigator site file or refer to the Sponsor contact information provided on the title page). 
An independent Clinical Event Committee (CEC) will conduct a medical review and adjudicate at a 
minimum all CRT-D/CRT-P system and procedure-related adverse events, all CSPOT system and 
procedure-related adverse events, all cardiovascular related AEs (regardless of seriousness), all SAEs 
and all AEs with a fatal outcome. The CEC will consist of non-Medtronic employed physicians that are 
not participating investigators for the study. 
 
Table 11: Adverse Event Classification Responsibilities 

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What is classified? 
Who classifies? 
Classification Parameters 
Relatedness 
Investigator 
• 
CRT-D/CRT-P Procedure Related 
• 
CRT-D/CRT-P System Related 
• 
CSPOT System Related 
Sponsor 
• 
CRT-D/CRT-P Procedure Related 
• 
CRT-D/CRT-P System Related 
• 
CSPOT System Related 
• 
Complication or Observation (for all system or procedure 
related AEs) 
CEC 
• 
CRT-D/CRT-P Procedure Related 
• 
CRT-D/CRT-P System Related 
• 
CSPOT System Related 
• 
Not Related 
• 
Cardiovascular related 
• 
Complication or Observation (for all system or procedure 
related AEs) 
Seriousness 
Investigator 
SAE, DD with SADE potential 
Sponsor 
SAE, UADE/USADE, DD 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 
CEC 
Sudden Cardiac, Non-sudden Cardiac, Non-Cardiac, Unknown 
 
 
12.5.3 Adverse Event and Device Deficiency Reporting Requirements 
Regulatory reporting of AEs and DDs will be recorded and reported according to local regulatory 
requirements. It is the responsibility of the Investigator and the sponsor to abide by the AE reporting 
requirements stipulated by local law and the study site’s EC. 
 
Table 12: Reporting Requirements 
 
Unanticipated Adverse Device Effect (UADE), Unanticipated Serious Adverse Device Effects (USADE) 
Investigator submit to: 
Medtronic 
Submit as soon as possible as per local reporting requirement, but not later 
than within 10 working days after the investigator first learns of the event. 
IRB/Ethics Committee 
Submit per local reporting requirement. 

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Regulatory Authorities 
Submit per local reporting requirement. 
Sponsor submit to: 
Regulatory Authorities 
Submit per local reporting requirement. 
IRB/Ethics Committee 
Submit per local reporting requirement. 
Serious Adverse Events (SAE) in EEA & UK 
Investigator submit to: 
Medtronic 
Submit as soon as possible as per local reporting requirement, but not later 
than within 3 calendar days after the  study personnel’s awareness of the 
event. 
IRB/Ethics Committee 
Submit per local reporting requirement. 
Regulatory Authorities 
Submit per local reporting requirement. 
Sponsor submit to: 
Regulatory Authorities 
Submit per local reporting requirement. 
IRB/Ethics Committee 
Submit per local reporting requirement. 
AEs, Serious Adverse Events in U.S. (SAE)/ Adverse Device Effects (ADE), SADE, Deaths 
Investigator submit to: 
Medtronic 
Submit as soon as possible as per local reporting requirement, but not later 
than within 10 working days after the investigator first learns of the event. 
Regulatory Authorities 
Submit per local reporting requirement. 
IRB/Ethics Committee 
Submit per local reporting requirement. 
Sponsor submit to: 
Regulatory Authorities 
Submit per local reporting requirement. 
IRB/Ethics Committee 
Submit per local reporting requirement. 
Device Deficiency (DD)/Device Deficiency with SADE potential 
Investigator submit to: 
Medtronic 
Submit as soon as possible as per local reporting requirement, but not later 
than 3 days after the investigator first learns of the event or of new 
information in relation with an already reported event. 
Regulatory Authorities 
Submit per local reporting requirement. 
IRB/Ethics Committee 
Submit per local reporting requirement. 

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Sponsor submit to: 
Regulatory Authorities 
Submit per local reporting requirement. 
IRB/Ethics Committee 
Submit per local reporting requirement. 
 
 
12.6 Subject Death 
All subject deaths must be reported by the investigator to Medtronic on an AE eCRF (AE with outcome 
of fatal) as soon as possible after the investigator first learns of the death. 
In the event of a subject’s death, it is recommended that the implanted system be explanted and 
returned to Medtronic for analysis whenever possible per local process. Local laws and procedures 
must be followed where applicable. If any system component is returned to Medtronic, internal return 
product reporting systems may be used to gather additional information about the returned 
device/component. 
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, if available should be sent to the Medtronic clinical study team. If an 
autopsy is conducted, a copy of 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 study site, it is the 
investigative study site’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 
• 
Relatedness to CRT-P/CRT-D system and/or procedure 
• 
Relatedness to CSPOT system 
• 
Device interrogation information/reports and .pdd file information/reports (if available) 
• 
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 allowed by state/local law) 
 
12.6.1 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: 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 

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onset cannot be determined, Sudden Cardiac Death will 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 Death Classification: Unknown death classification is intended for use only when 
there is insufficient or inadequate information to classify the death. 
 
Table 13: Subject death classification responsibilities 
 
What is classified? 
Who classifies? 
Classification Parameters 
Relatedness 
Investigator 
• 
CRT-D/CRT-P Procedure related 
• 
CRT-D/CRT-P System related AEs 
• 
CSPOT System related 
• 
Not related 
• 
Possibly Related 
• 
Probably Related 
• 
Causal Related 
Death Classification 
Investigator 
Sudden Cardiac, Non-sudden Cardiac, Non-cardiac, Unknown 
 
The CEC will review all AEs with a fatal outcome and provide a final adjudication of both cardiovascular 
event and death classification. Regulatory reporting of subject deaths will be completed according to 
local regulatory requirements. 
12.7 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. The reporting of product complaints by the clinical team must be done according to the local 
Standard Operating Procedures. Medtronic will notify the RAs (e.g., CA) as applicable for the following 
incidents immediately upon learning of them and is not limited to AEs and DDs only: 

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• 
Any malfunction or deterioration in the characteristics and/or performance of a 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. 
• 
Any serious deterioration in the state of health, including: 
 
Life-threatening illness or injury 
 
Permanent impairment of a body function or permanent damage to a body 
structure 
 
A condition necessitating medical or surgical intervention to prevent permanent 
impairment of a body function or permanent damage to a body structure 
 
 
13. 
Data Review Committees 
 
 
13.1 Clinical Events Committee 
The study will utilize an Independent Clinical Events Committee (CEC) to adjudicate a subset of all the 
adverse events collected in the study for an unbiased assessed of those related to the device or 
system. At regular intervals, an independent CEC will conduct a medical review at a minimum all CRT- 
D/CRT-P system and procedure-related adverse events, all CSPOT system related, cardiovascular 
related AEs, all SAEs and all AEs with a fatal outcome of participants in the study. 
The CEC will consist of a minimum of three (3) non-Medtronic employed physicians that are not 
participating investigators for the study, including a CEC chairperson. At least three CEC members 
must adjudicate, at a minimum, all adverse events that are related to CRT-D/CRT-P system and/or 
procedure, CSPOT system, and/or cardiovascular related events. All SAEs, adverse events with 
outcome of death, and cardiovascular events will be reviewed by one CEC Member.  If the one physician 
CEC member deems an event to be related, it will then go to three CEC member adjudication. The CEC 
will operate under a charter that documents the process of adjudication of data for this study. 
Medtronic personnel may facilitate and participate in an CEC meeting but will be non-voting members. 
If the CEC disagrees with the investigator’s classification of the event, the rationale will be provided to 
the investigator. If the investigator agrees with the CEC’s adjudication, the CRF documenting the AE 
will be updated accordingly. 
If the investigator does not agree with the CEC’s adjudication classification, both determinations will be 
provided within the final report; however, the CEC’s adjudication will be used for data analysis. The 
disagreement will also be included in reporting to ECs and regulatory authorities, if required. 
Source documents to support adjudication may be requested. 

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14. 
Statistical Design and Methods 
 
The CSPOT study is a prospective, non-randomized, multi-center, global, feasibility clinical study 
designed to assess different approaches to resynchronization in CRT-indicated patients. 
The study may enroll up to 60 subjects at up to 12 sites in the US and Europe, with no more than 15 
subjects enrolled per site.  The site maximum of 15 subjects will ensure that evidence generated by this 
study is not overly dependent on a single site. Study subjects will be followed for 6 months after the 
utilization of the CSPOT Research System and acute pacing protocol. 
 
 
14.1 General Aspects of Analysis 
Medtronic statisticians or designees will perform all statistical analyses. 
The study is exploratory in nature. A separate Statistical Analysis Plan (SAP) will be developed and 
include a comprehensive description of the statistical methods and analyses to be included in the final 
study report. Any change to the data analysis methods described in the protocol will require an 
amendment only if it changes a principal feature of the protocol. Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be described in the 
clinical study report. 
Descriptive statistics will be used to summarize the subject demographic and clinical 
characteristics at baseline. Data for qualitative variables will be presented as incidence 
rates (total number of subjects, number of events, and percent). Data for continuous 
variables will be summarized using measures of central tendency and dispersion. 
P-values for hypothesis testing will be evaluated based on a two-sided significance level of 
0.05. No adjustments will be made for multiple testing because of the exploratory 
nature of this study. 
No imputation of missing data is planned, but missingness will be summarized as a binary variable. In 
addition, if the positive dP/dt max or SDAT measurements meant to be observed during the CSPOT 
protocol are missing for some patients, additional analysis to characterize baseline factors associated 
with missing data may be considered. 
All subjects who signed the informed consent document will be defined as the Enrolled Cohort. The 
Analysis Cohort is defined as subjects who are enrolled, do not violate any inclusion or exclusion 
criteria, and have all leads successfully placed during the CSPOT Acute Pacing Protocol. This may 
include patients that do not successfully complete CRT implant or the 6-month follow-up visit. The 
Analysis Cohort will be used for the primary analysis approach for all objectives unless otherwise noted. 
Subjects in the Enrolled Cohort but not the Analysis Cohort will not be included in the primary analyses 
of the objectives described here, but will be reported in a subject disposition table, and may be included 
in some secondary analysis approaches. 

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14.2 Analysis Execution 
Analysis for CSPOT will occur after the last subject has been exited or upon study closure determine by 
the sponsor. Analysis will include both primary and all secondary objectives. Ancillary objectives will be 
addressed based on available data. A final report will be prepared once all data collection has ended and 
all subjects have completed the 6-month follow-up visit or have been exited. 
14.3 Interim Analysis 
No interim analyses are planned for this study. 
14.4 Primary Objectives 
This study has two primary objectives, both based on data collected at implant. One compares 
electrical synchronization among pacing configurations using SDAT, measured by the ECG belt, and 
one compares hemodynamic response among configurations using LV dP/dt max, measured by the 
pressure catheter. Each objective entails two statistical hypotheses between pacing configurations: 
CSPOT vs. CSP-only and CSPOT vs. Traditional CRT. 
14.4.1 Primary Objective #1 
Two statistical hypothesis tests will be used to evaluate this objective. The null and alternative 
hypotheses for the first test are: 
H0: Improvement in SDAT relative to baseline in the CSPOT pacing configuration = Improvement in 
SDAT relative to baseline in the CSP-only configuration  
HA: Improvement in SDAT relative to baseline in the CSPOT pacing configuration ≠ Improvement in 
SDAT relative to baseline in the CSP-only configuration 
The bipolar CSP-only configuration will be used in this comparison.  
The null and alternative hypotheses for the second test are: 
H0: Improvement in SDAT relative to baseline in the CSPOT pacing configuration = Improvement in 
SDAT relative to baseline in the traditional CRT configuration 
HA: Improvement in SDAT relative to baseline in the CSPOT pacing configuration ≠ Improvement in 
SDAT relative to baseline in the traditional CRT configuration 
For both hypothesis tests, the best LV cathode, chosen for the CSPOT configuration, as described in 
Section 10.6.1, will be used.  
Paired two-sided t-tests are planned to test the hypotheses, but a Wilcoxon signed-rank test will be 
considered as an additional analysis approach. 
14.4.2 Primary Objective #2 
Two statistical hypothesis tests will be used to evaluate this objective. 
The null and alternative hypotheses for the first test are: 
H0: Improvement in positive LV dP/dt max relative to baseline in the CSPOT pacing configuration = 
Improvement in positive LV dP/dt max relative to baseline in the CSP-only configuration 
HA: Improvement in positive LV dP/dt max relative to baseline in the CSPOT pacing configuration ≠ 
Improvement in positive LV dP/dt max relative to baseline in the CSP-only configuration 

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The bipolar CSP-only configuration will be used in this comparison. A paired two-sided t-test is planned 
to test this hypothesis. 
The null and alternative hypotheses for the second test are: 
H0: Improvement in positive LV dP/dt max relative to baseline in the CSPOT pacing configuration = 
Improvement in positive LV dP/dt max relative to baseline in the traditional CRT configuration 
HA: Improvement in positive LV dP/dt max relative to baseline in the CSPOT pacing configuration ≠ 
Improvement in positive LV dP/dt max relative to baseline in the traditional CRT configuration 
For both hypothesis tests, the best LV cathode, chosen for the CSPOT configuration, as described in 
Section 10.6.1, will be used.  
Paired two-sided t-test are planned to test the hypotheses, but a Wilcoxon signed-rank test will be 
considered as an additional analysis approach. 
For each subject and each pacing configuration, multiple positive LV dP/dt max measurements will be 
taken because individual measurements are known to be highly variable. The primary analysis approach 
for this hypothesis test will summarize these measurements to one value for each subject-pacing 
configuration combination. However, a repeated measures analysis of the individual measurements 
may also be considered as additional analysis. 
14.5 Secondary Objectives 
The following secondary objectives will all be evaluated, regardless of their results or the results of the 
primary objectives, given the exploratory nature of this study. 
14.5.1 Secondary Objective #1 
 
Descriptive summary statistics of SDAT improvement relative to baseline (mean, 95% confidence 
interval, median, 25th and 75th percentile, and minimum and maximum) will be calculated for each 
combination of pacing configuration, measurement, and subpopulation. 
Subjects missing the data required to assign them to a subgroup for this objective (i.e. QRS width, 
conduction disorder presence, cardiomyopathy etiology) will not be included in either subgroup. 
14.5.2 Secondary Objective #2 
Descriptive summary statistics of positive LV dP/dt max improvement relative to baseline (mean, 95% 
confidence interval, median, 25th and 75th percentile, and minimum and maximum) will be calculated 
for each combination of pacing configuration, measurement, and subpopulation.  
Subjects missing the data required to assign them to a subgroup for this objective (i.e. QRS width, 
conduction disorder presence, cardiomyopathy etiology) will not be included in either subgroup. 
14.5.3 Secondary Objective #3 
For each subject with LVEF measured at implant and 6-month visit, LVEF change will be calculated as 
an absolute change from baseline: 
(EF measured at 6 months) − (EF measured at baseline) 
LVEF change will then be summarized with mean, 95% confidence interval, median, 25th and 75th 
percentile, and minimum and maximum. 

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Subjects will be included in this analysis only if they are in the Analysis Cohort and successfully 
complete CRT implant and the 6-month follow-up visit. 
14.5.4 Secondary Objective #4 
For each subject with LVESV measured at implant and 6-month visit, LVESV change will be calculated 
as a relative change from baseline: 
 
(LVESV measured at 6 months) −(LVESV measured at baseline)
LVESVI measured at baseline
 
 
LVESV change will then be summarized with mean, 95% confidence interval, median, 25th and 75th 
percentile, and minimum and maximum. 
Subjects will be included in this analysis only if they are in the Analysis Cohort and successfully 
complete CRT implant and the 6-month follow-up visit. 
14.5.5 Secondary Objective #5 
The Clinical Composite Score (CCS) is a 3-level categorical variable that can take the values – 
Improved, Unchanged, or Worsened – at each follow-up visit. It is based on mortality, HF events, 
termination of device function, NYHA score, and patient global assessment. The count and proportion 
of subjects with each of these CCS values based on the 6-month visit will be provided. 
Subjects will be included in this analysis only if they are in the Analysis Cohort and have an observed 
CCS. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
14.8 Sample Size Determination 

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Because this is an exploratory feasibility study, sample size has been determined by the number of 
possible sites, enrollment rates and timing for completion. 
 
 
15. 
Ethics 
 
 
15.1 Statement(s) of Compliance 
This study will be conducted in compliance with international ethical and scientific quality standards, 
known as GCP. GCP includes review and approval by an independent EC before initiating a study, 
continuing review of an ongoing study by an EC, and obtaining and documenting the freely given 
informed consent of a subject before initiating the study. 
The CSPOT study was designed to reflect the GCP principles outlined in ISO 14155:2020 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 14155:2020, the sponsor shall avoid improper influence on, or inducement of, the 
subject, monitor, any investigator(s) or other parties participating in, or contributing to, the clinical 
investigation. 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. AE and DD handling in the CSPOT study is ISO 14155:2020 compliant for all participating 
geographies. 
The principles of the DoH have been implemented through the IC process, EC approval, study training, 
clinical trial registration, pre-clinical testing, risk-benefit assessment and publication policy. 
Ultimately, all study sites in all geographies will follow and comply with: 
• 
Principles of DoH 
• 
21 CFR Part 11 (Electronic Records, Electronic Signatures) 
• 
21 CFR Part 54 (Financial Disclosure by Clinical Investigators) 
• 
The CTA 
• 
The procedures described within this CIP 
• 
Local EC Requirements 

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In addition to the regulatory requirements outlined above, the study will be conducted according to 
federal, national and local laws, regulations, standards, and requirements of the countries/geographies 
where the study is being conducted. These include but are not limited to: 
• 
In the United States, the study will be conducted under an FDA IDE in compliance with 
21 CFR Parts: 
 
50: Protection of Human Subjects 
 
54: Financial Disclosure by Clinical Investigators 
 
56: IRBs 
 
812: IDEs 
• 
In Europe the study will be conducted in compliance with the local regulations 
 
The study will be publicly registered prior to in accordance with the 2007 FDAAA and DoH on 
http://clinicaltrials.gov (PL 110-85, section 810(a)). In addition, the study may be registered in local 
regulatory databases where required by local law. 
Approval of the CIP and CIP amendments is required from the following groups prior to any study 
procedures at a study site: 
• 
Medtronic 
• 
Principal Investigators (where required by local law/regulations) 
• 
Geography-specific regulatory authorities (if regulatory approval is required) 
• 
An independent medical EC or IRB. 
Similarly, approval of subsequent revisions to the CIP is required at each study site from the above- 
mentioned groups prior to implementation of the revised CIP at the study site. 
 
 
16. 
Study Administration 
 
 
16.1 Monitoring 
It is the responsibility of Medtronic to ensure proper monitoring of this study. Trained Medtronic 
personnel or delegates appointed by Medtronic may perform study monitoring at the study site in 
order to ensure that the study is conducted in accordance with the CIP, the CTA, and the applicable 
regulatory and local requirements. Medtronic, or delegates, must therefore be allowed direct access to 
the subjects’ case histories (clinic and hospital records, and other source data/documentation) upon 
request as per the IC, Research Authorization (where applicable) and CTA. The principal investigator 
should also be available during monitoring visits. 
16.1.1 Monitoring Visits 
Frequency of monitoring visits may be based upon subject enrollment, study compliance, number of 
adverse events, number of deviations, observations from previous monitoring visits and any suspected 
inconsistency in data that requires investigation. Regulatory documents may be reviewed at each 

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study site. Monitoring for the study, including, site initiation visits, interim monitoring visits, and 
closeout visits will be done in accordance to the study-specific monitoring plan. 
Monitoring visits may be conducted periodically to assess study site progress, the investigator’s 
adherence to the CIP, regulatory compliance including but not limited to EC approval and review of the 
study, maintenance of records and reports, and review of source documents against subject CRFs in 
accordance to the study-specific monitoring plan. Monitors review study site regulatory and study 
compliance by identifying observations of non-compliance and communicating those observations 
along with recommendations for preventative/corrective actions to study site personnel.  Monitors 
may work with study personnel to determine appropriate corrective action recommendations and to 
identify trends within the study or at a particular study site. 
The Investigator will permit study related monitoring, audits, IRB review and regulatory inspections by 
providing direct access to source data and source documents. 
Medtronic will request that the study site upload identified subject case history files and regulatory 
documents to a secure, password-protected website prior to remote monitoring visits. 
16.2 Data Management 
Data will be collected using an electronic data management system for studies. eCRF data will be 
stored in a secure, password-protected database which will be backed up nightly. Data will be reviewed 
using programmed and manual data checks.  Data queries will be made available to study sites for 
resolution.  Study management reports may be generated to monitor data quality and study progress. 
At the end of the study, the data will be frozen 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. If it’s impossible to pseudonymize (where the subject’s name cannot be 
removed, such as fluoroscopy images) from the data carrier, data will not be transferred electronically. 
Procedures in the CIP require source documentation. Source documentation will be maintained at the 
study site. Source documents, which may include worksheets, subject medical records, programmer 
printouts, and interrogation files, must be created and maintained by the investigational study site 
team. 
The investigator will clearly mark clinical records to indicate that the subject is enrolled in this clinical 
investigation. 
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. See Section 16.3 for CRFs and 
data collection elements that may be considered source. 
Device data from transmissions and any save-to-disk data collected at office visits will be sent to 
Medtronic. Upon receipt, device data will be maintained with databases and retrieved for analysis and 
reporting. 
Investigator will be required to sign off on all entered and completed data on the eCRF. 

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16.3 Direct Access to Source Data/Documents 
Medtronic may conduct audits at participating study sites. The purpose of an audit is to verify the 
performance of the monitoring process and the study conduct, independently of the personnel directly 
involved in the study. RAs, such as the FDA, may also perform inspections at participating study sites. 
The investigator and/or institution shall permit Medtronic, ECs and RAs direct access to source data 
and documents during monitoring, audits and regulatory inspections. 
16.4 Confidentiality 
All information and data sent to parties involved in study conduct concerning subjects or their 
participation in this study will be considered confidential. Study sites will assign a unique SID to each 
subject. Records of the subject/SID relationship will be maintained by the study site. The SID number is 
to be recorded on all study documents to link them to the subject’s medical records at the study site. 
Confidentiality of data will be observed by all parties involved at all times throughout the clinical 
investigation. All data shall be secured against unauthorized access. The privacy of each subject and 
confidentiality of his/her information shall be preserved in reports and when publishing any data. In the 
US, “Protected Health Information” (PHI) will be maintained in compliance with the HIPAA of 1996. To 
maintain confidentiality, the subject’s name or any other PHI should not be recorded on any study 
document other than the IC. This scenario will be covered in the IC. In the event a subject’s name/PHI is 
included for any reason, it will be blinded as applicable. In the event of inability to blind the identification 
(e.g., digital media, fluoroscopy images), it will be handled in a confidential manner by the authorized 
personnel. Data relating to the study might be made available to third parties (for example in case of an 
audit performed by RA), provided the data are treated as confidential and that the subject’s privacy is 
guaranteed. No identifiable subject information will be published. 
16.5 Liability/Warranty/Insurance Information 
16.5.1 Warranty 
Warranty information will be provided in the product packaging for the investigational or commercially 
released system and components and will be available upon request. 
Medtronic maintains appropriate clinical study 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 study insurance statement/certificate will be provided to the IRB/EC. 
16.5.2 Insurance (Europe) 
Medtronic Bakken Research Site B.V. is a wholly owned subsidiary of Medtronic, which as the parent 
company of such entity maintains appropriate clinical study 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 EC. 

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16.6 CIP Amendments 
Any revisions or amendments to documents that are submitted to the competent authorities 
(including CIP and IC) along with a statement of justification for the changes, will be submitted to all 
affected RAs (FDA, CA) and governing ECs, according to applicable regulations. All amendments to the 
CIP shall be agreed upon between Medtronic and the principal investigator(s), or the coordinating 
investigator. Approval by regulatory agencies and ECs (where applicable) must be obtained prior to 
implementing a CIP revision at the study site. 
16.7 Record Retention 
All study-related documents must be retained for a period of at least 2 years after end of study in 
his/her region and after study closure (or longer if required by local law). Medtronic will inform the 
investigator/study site when these documents are no longer required to be retained. 
No study document or image will be destroyed without prior written agreement between Medtronic 
and the investigator. The investigator should take measures to prevent accidental or premature 
destruction of documents. Should the investigator wish to assign the study records to another party or 
move them to another location, advance written notice must be given to Medtronic. 
Medtronic will retain the study records according to Medtronic corporate policy and record retention 
schedule. 
16.7.1 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) or the date that the records are no longer 
required for purposes of supporting a pre-market approval application. 
• 
All correspondence between the EC/IRB, sponsor, monitor, FDA, RA and the 
investigator that pertains to the investigation, including required reports. 
• 
Subject’s case history records, including: 
 
Signed and dated IC: 
• 
U.S.: signed by subject. 
• 
Europe: signed by subject and investigator. 
 
Observations of AEs/ADEs/DDs 
 
Medical history 
 
Baseline, Implant, CSPOT system protocol and follow up data (if applicable) 
 
Documentation of the dates and rationale for any deviation from the protocol 
• 
List of investigation study sites 
• 
FD (if applicable) 

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• 
Subject screening log & ID log (if applicable) 
• 
Normal value(s)/range(s) for clinical laboratory test (if applicable) 
• 
Lab certificate (if applicable) 
• 
Device Disposition Logs (if applicable). 
• 
Non implantable device Disposition Logs (if applicable) 
• 
All approved versions of the CIP, IC, IBs/Report of Prior Investigation Summary 
• 
Fully executed CTA. 
• 
CV (signed and dated in Europe only) of principal investigators and key members of 
investigation study site team (as required by applicable regulations). 
• 
Documentation of delegated tasks. 
• 
EC approval documentation. Written information that the investigator or other study 
staff, when member of the EC, did not participate in the approval process. Approval 
documentation must include the ECs composition, where required per local law. 
• 
RA notification, correspondence and approval, where required per local law. 
• 
Study training records for study site staff. 
• 
Insurance certificates (Europe only). 
• 
Any other records that FDA and local regulatory agencies require to be maintained. 
• 
Final Study Report including the statistical analysis. 
 
16.7.2 Sponsor Records 
Medtronic shall maintain the following accurate, complete, and current records: 
• 
All correspondence which pertains to the investigation 
• 
Investigational device traceability record containing Model and serial numbers of 
devices, shipping date and name and address of person that received shipped device, 
location (if different than person shipped to), transfer and receipt by Medtronic dates (if 
applicable) 
• 
Non implantable device traceability records containing Model and serial/lot numbers, 
shipping date and name and address of person that received shipped device, location (if 
different than person shipped to), transfer and receipt by Medtronic dates (if applicable) 
• 
Sample of label attached to investigational device 
• 
Signed Investigator Trial Agreements, FD (if applicable) and current signed and dated 
(Europe only) CV of principal investigator and key members of the investigation study 
site team (as required by local law) 
• 
All approved IC templates, and other information provided to the subjects and 
advertisements, including translations 
• 
Copies of all EC approval letters and relevant EC correspondence and EC voting 
list/roster/letter of assurance 

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• 
Names of the institutions in which the study will be conducted 
• 
RA correspondence, notification and approval as required by national legislation 
• 
Insurance certificates (Europe only) 
• 
Names/contact addresses of monitors 
• 
Monitoring visit reports 
• 
Statistical analyses and underlying supporting data 
• 
Final report of the study 
• 
The CIP, IB/Report of Prior Investigations summary and study related reports, and 
revisions 
• 
Study training records for study site personnel and Medtronic personnel involved in the 
study 
• 
Any other records that local regulatory agencies require to be maintained. 
 
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 indefinitely. 
16.8 Reporting Requirements 
16.8.1 Investigator Reports 
The investigator is responsible for the preparation (review and signature) and submission to the 
sponsor of all case report forms, adverse events and adverse device effects (reported per the country- 
specific collection requirements), device deficiencies, deaths, and any deviations from the clinical 
investigation plan. If any action is taken by an EC with respect to this 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 Section 12.5.3. The investigator shall 
prepare and submit in a complete, accurate and timely manner the reports listed in this section. 
 
Table 14: Investigator reports applicable for all geographies per Medtronic requirements 

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Report 
Submit to 
Description/Constraints 
Withdrawal of IRB/EC 
approval 
Sponsor and 
Relevant 
Authorities 
The investigator must report a withdrawal of approval by the 
reviewing IRB/EC of the investigator’s part of the 
investigation within 5 working days. 
Study Deviations 
Sponsor and 
IRB/EC 
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/ECs and 
Relevant 
Authorities 
This report must be submitted within 3 months of study 
completion or termination. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 15: Additional Investigator reports applicable to the United States per FDA regulations 

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Report 
Submit to 
Description/Constraints 
Withdrawal of IRB/EC 
approval (either 
suspension or 
termination) 
Sponsor 
The investigator must report a withdrawal of approval by the 
reviewing IRB/EC of the investigator’s part of the 
investigation within 5 working days.  (21 CFR 812.150(a)(2)) 
Progress report 
Sponsor and 
IRB/EC 
The investigator must submit this report to the sponsor and 
IRB/EC at regular intervals, but in no event less than yearly 
intervals. (21 CFR 812.150 (a)(3)). 
Study deviations 
Sponsor and 
IRB/EC 
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/EC, and the FDA/applicable RA.  If the deviation does not 
affect these issues then only Medtronic must approve it. (21 
CFR 812.150(a)(4)) 
Failure to obtain IC 
prior to 
investigational device 
use 
Sponsor and 
IRBs/ECs 
If an investigator uses a device without obtaining IC, the 
investigator shall report such use within 5 working days after 
device use. (21 CFR 812.150(a)(5)) 
Final report 
Sponsor 
IRBs/ECs 
Relevant 
Authorities 
This report must be submitted within 3 months of study 
completion or termination of the investigation or 
completion or termination of the investigator’s part of the 
investigation. (21 CFR 812.150(a)(6)) 
Other 
IRB/EC and FDA 
An investigator shall, upon request by a reviewing IRB/EC, 
FDA or any other RA, provide accurate, complete, and 
current information about any aspect of the investigation. 
(21 CFR 812.150(a)(7)) 

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Table 16: Investigator reports applicable to Europe per ISO 14155 
 
Report 
Submit to 
Description/Constraints 
Withdrawal of IRB/EC 
approval 
Sponsor 
Report if required by local law. 
Progress Report 
Sponsor and 
IRB/EC 
Provide if required by local law or IRB/EC. 
Study Deviations 
Sponsor, 
Competent 
Authority and 
IRB/EC 
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, CAs or the 
appropriate RAs should be informed. (ISO 14155:2020) 
Failure to obtain IC 
Sponsor and 
IRBs/ECs 
IC shall be obtained in writing and documented before a 
subject is enrolled into the clinical investigation.  (ISO 
14155:2020) 
 
16.8.2 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 
the reviewing EC, RA or FDA, provide accurate, complete and current information about any aspect of 
the investigation. Safety data Medtronic reporting requirements are listed in section 12.5.3. 
Table 21: Sponsor reports for Europe 
 
Report 
Submit to 
Description/Constraints 
Premature 
termination or 
suspension of the 
clinical investigation 
Investigators, 
IRB/EC, 
Relevant 
authorities and 
Head of the 
Institution 
Provide prompt notification of termination or suspension 
and reason(s). (ISO 14155:2020) 
Withdrawal of IRB/EC 
approval 
Investigators, 
Head of 
Institution, 
IRB/EC and 
relevant 
authorities 
Investigators, IRBs/ECs will be notified only if required by 
local laws or by the IRB/EC. 

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Report 
Submit to 
Description/Constraints 
Withdrawal of CA 
approval 
Investigators, 
Head of 
Institution, 
IRB/EC, and 
relevant 
authorities 
Investigators, IRBs/ECs will be notified only if required by 
local laws or by the IRB/EC. 
Progress Reports 
IRB/EC and 
RAs 
This will be submitted to the IRB/EC only if required by the 
IRB//EC). 
Final report 
Investigators, 
IRB/EC, and 
RAs if required 
For studies with study sites complying to 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). 
• 
The coordinating investigator shall sign the report. If 
no coordinating investigator is appointed, then the 
signature of the principal Investigator in each study 
site should be obtained.   (ISO 14155:2020) 
Study deviation 
Investigators 
Ensure that all deviations from the CIP are reviewed with the 
appropriate clinical investigator(s), are reported on the CRFs 
and the final report of the clinical investigation.  (ISO 
14155:2020) 
Study site specific study deviations will be submitted to 
investigators periodically. 
 
16.9 Publication and Use of Information 
Publications from the CSPOT study will be handled according to Standard Operating Procedures and as 
indicated in the CTA. 
16.9.1 Publication Committee 
Medtronic may form the CSPOT Publication Committee from 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, 5) review 
and prioritize publication proposals, 6) provide input on publication content, and 7) determine 

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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 at 
as needed. 
16.9.2 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 CIP. 
An ancillary publication is any publication that does not address the study objectives identified in the 
CIP.  They include publications proposed and developed by other Medtronic departments or entities, 
clinicians participating in this study, and clinicians not participating in this 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. 
The committee may decide that no publications, including abstracts, will be published prior to the end 
of the study or with individual study site 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. 
16.9.3 Criteria for Determining Authorship 
Publications will adhere to authorship criteria defined by the International Committee of Medical 
Journal Editors (ICMJE, Uniform requirements for manuscripts submitted to biomedical journals, 
www.icmje.org). Individual authorship 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 contributions to conception and design of the work, or the acquisition, 
analysis, or interpretation of data for the work; AND 
• 
Drafting the work or revising it critically for important intellectual content; AND 
• 
Final approval of the version to be published; AND 
• 
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. 
Decisions regarding authorship and contributor-ship 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 CSPOT 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. 

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16.9.4 Transparency 
Transparency of clinical 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 CAs of participating countries when required by local law 
• 
Registering and posting the study results on a <publicly accessible database, e.g., 
ClinicalTrials.gov> based on the posting rules stipulated 
• 
Submitting for publication the primary study results after the study ends 
• 
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 study sites study data accessible to the corresponding investigator 
after the completion of the study, if requested 
16.10 Suspension or Early Termination 
16.10.1 
Planned Study Closure 
Study Closure is a process initiated by distribution of a study closure letter. Study closure is defined as 
closure of a study that occurs when Medtronic and/or regulatory requirements have been satisfied per 
the CIP and/or by a decision by Medtronic or RA), whichever occurs first. The study closure process is 
complete upon distribution of the Final Report or after final payments, whichever occurs last. Ongoing 
EC/IRB oversight is required until the overall study closure process is complete. Upon study closure, 
subjects should be managed and followed per physician discretion. 
16.10.2 
Early Termination or Suspension 
Early Termination is the closure of a study that occurs prior to meeting defined endpoints. This is 
possible for the whole study or a single study site.  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 study site. 
16.10.2.1 
Study-wide termination or suspension 
Possible reasons for considering study-wide suspension or termination of the study include but are not 
limited to: 
• 
AEs 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 RA (where the study is operating under RA) 
• 
Technical issues during the manufacturing process 

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16.10.2.2 
Investigator/study site termination or suspension 
Possible reasons for investigator or study site termination or suspension include but are not limited to: 
• 
Failure to obtain initial EC approval or annual renewal of the study 
• 
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 CTA (e.g. failure to submit data in a 
timely manner, failure to follow-up on data queries and monitoring observations in a 
timely manner, etc.) 
• 
EC suspension of the study site 
• 
Fraud or fraudulent misconduct is discovered (as defined by local law and regulations) 
• 
Investigator request (e.g. no longer able to support the study) 
 
16.10.3 
Procedures for Termination or Suspension 
16.10.3.1 
Medtronic-initiated and regulatory authority-initiated 
• 
Medtronic will promptly inform the clinical investigators of the termination or 
suspension and the reasons and inform the RAs where required 
• 
In the case of study termination or suspension for reasons other than a temporary EC 
approval lapse, the investigator will promptly inform the EC 
• 
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 
16.10.3.2 
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 EC 
• 
The investigator will promptly inform the regulatory authorities 
• 
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 

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16.10.3.3 
Ethics Committee-initiated 
• 
The investigator will inform Medtronic and provide a detailed written explanation of the 
termination or suspension within 5 business days 
• 
Subject enrollment must stop until the suspension is lifted 
• 
Subjects already enrolled should continue to be followed in accordance with EC 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 
 
 
17. 
References 
 
 
1. 
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. 7(2): p. 176-82. 
2. 
Packer, M., Development and Evolution of a Hierarchical Clinical Composite End Point for the 
Evaluation of Drugs and Devices for Acute and Chronic Heart Failure: A 20-Year Perspective. 
Circulation, 2016. 134(21): p. 1664-1678. 
3. 
Lustgarten, D.L., et al., His-bundle pacing versus biventricular pacing in cardiac resynchronization 
therapy patients: A crossover design comparison. Heart Rhythm, 2015. 12(7): p. 1548-57. 
4. 
Ajijola, O.A., et al., Permanent His-bundle pacing for cardiac resynchronization therapy: Initial 
feasibility study in lieu of left ventricular lead. Heart Rhythm, 2017. 14(9): p. 1353-1361. 
5. 
Arnold, A.D., et al., His Resynchronization Versus Biventricular Pacing in Patients With Heart Failure 
and Left Bundle Branch Block. J Am Coll Cardiol, 2018. 72(24): p. 3112-3122. 
6. 
Upadhyay, G.A., et al., On-treatment comparison between corrective His bundle pacing and 
biventricular pacing for cardiac resynchronization: A secondary analysis of the His-SYNC Pilot Trial. 
Heart Rhythm, 2019. 16(12): p. 1797-1807. 
7. 
Vijayaraman, P., et al., His-Optimized Cardiac Resynchronization Therapy to Maximize Electrical 
Resynchronization: A Feasibility Study. Circ Arrhythm Electrophysiol, 2019. 12(2): p. e006934. 
8. 
Boczar, K., et al., Cardiac resynchronization therapy with His bundle pacing. Pacing Clin 
Electrophysiol, 2019. 42(3): p. 374-380. 
9. 
Deshmukh, A., et al., Sequential His bundle and left ventricular pacing for cardiac resynchronization. J 
Cardiovasc Electrophysiol, 2020. 31(9): p. 2448-2454. 
10. 
Huang, W., et al., A Novel Pacing Strategy With Low and Stable Output: Pacing the Left Bundle 
Branch Immediately Beyond the Conduction Block. Can J Cardiol, 2017. 33(12): p. 1736 e1-1736 e3. 
11. 
Zhang, W., et al., Cardiac resynchronization therapy by left bundle branch area pacing in patients 
with heart failure and left bundle branch block. Heart Rhythm, 2019. 16(12): p. 1783-1790. 
12. 
Li, X., et al., Left bundle branch area pacing delivery of cardiac resynchronization therapy and 
comparison with biventricular pacing. ESC Heart Fail, 2020. 7(4): p. 1711-1722. 
13. 
Wang, Y., et al., The efficacy of left bundle branch area pacing compared with biventricular pacing in 
patients with heart failure: A matched case-control study. J Cardiovasc Electrophysiol, 2020. 31(8): p. 
2068-2077. 

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14. 
Epstein, A.E., et al., ACC/AHA/HRS 2008 Guidelines for device-based therapy of cardiac rhythm 
abnormalities. Heart Rhythm, 2008. 5(6): p. e1-62. 
15. 
Sterlinski, M., et al., In Heart Failure Patients with Left Bundle Branch Block Single Lead MultiSpot 
Left Ventricular Pacing Does Not Improve Acute Hemodynamic Response To Conventional 
Biventricular Pacing. A Multicenter Prospective, Interventional, Non-Randomized Study. PLoS One, 
2016. 11(4): p. e0154024. 
 
 
18. 
Appendices 
 
 
18.1 Informed Consent Template 
Patient informed consent form templates will be provided under separate cover. 
 
18.2 Data Collection Elements (Electronic Case Report Forms) 
Electronic Case Report Forms for the CSPOT study will be provided under separate cover. Final eCRFs 
will be provided to sites via the electronic data management system after the site has fulfilled all 
requirements for database access. 
18.3 Participating Investigators and Institutions 
A complete list of participating investigators and institutions (including names, titles/professional 
positions, address(es), and telephone numbers) where study activities will be conducted will be 
distributed under a separate cover when available. Approval of the CSPOT Study CIP will be 
documented by signing the Clinical Trial Agreement or a separate investigator agreement. 
 
18.4 IRB Committee List 
A complete list of participating IRBs and the Chairperson(s) will be provided under separate cover. 
This information will be updated throughout the course of the study. The updated list will be 
maintained at Medtronic and will be available upon request. 
18.5 Committees 
The CSPOT study will utilize an Event Adjudication Committee (CEC) for the assessment of all 
procedure and system related AEs, All SAEs, Cardiovascular related AEs and AEs with a fatal outcome. 
The CSPOT study may utilize a Publication Committee aiming to manage study publications. 
A Data Monitoring Committee (DMC) is not needed for this study. This decision was made based on 
the following criteria: it is felt there are no additional benefits of a DMC reviewing the data in addition to 
the Event Adjudication Committee (CEC) 
The updated member lists will be maintained at Medtronic and will be made available upon request. 

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18.6 Labeling 
Labeling for the CSPOT investigational components will be provided under separate cover. Labeling for 
all system components used in this study can be found with each package insert and/or will be available 
on http://manuals.medtronic.com. 
 
 
18.7 Foreseeable Adverse Events List (FAL) 
The information provided in this section pertains to foreseeable adverse events that may be observed in 
the CSPOT Feasibility Study and may collectively assist in identifying those events for a given device 
or therapy that are unexpected in nature. The foreseeable adverse events information consists of 
three parts: 1) observed adverse system effect(s) in comparable Medtronic studies, 2) adverse 
events reported in published literature, and3) additional foreseeable adverse events. An evaluation 
of potentially anticipated events observed in previous clinical studies and reported events in 
literature maybe used in combination with device labeling, manuals, current event reporting 
information, and other published data to assess for an unexpected occurrence. 
The implementation of the CSPOT Research System involves surgery, therefore, standard adverse 
events associated with a surgical procedure maybe experienced (e.g., anesthesia complications, 
injury, infections, bleeding, exacerbation of pre-existing conditions, healing complications, etc.). 
However, the focus of this section is to address in more detail, those events that are foreseeable due 
to the implementation, use, performance, and/or presence of the system under investigation. 
Potential risks associated with the implementation of the CSPOT Research System as well as risk 
minimization are discussed within Section 11.1 and 11.2.  Treatment required for procedure and/or 
system related adverse events may include medication, system reprogramming, system 
modification (e.g., repositioning, surgical abandonment, surgical removal), or other surgical and 
medical remedies. 
 
18.7.1 Observed Adverse System Effects in Previous Clinical Studies and Adverse Events 
Reported in Literature 
The CSPOT Research System has not been used previously in a clinical study. Preclinical testing has 
been performed using the CSPOT Research System, including design verification 
testing, design validation testing and a hazard analysis. Review/analysis activities 
included confirmation of appropriate content in the labelling and specifications of individual 
components.  Benchtop testing activities included checking the connections, use and 
performance of the individual components into a functional system. No adverse effects or 
malfunctioning were discovered. 
The CSPOT Research System facilitates the interconnection between pacing devices and 
permanently implanted leads targeting selected pacing locations in the patient’s right and/or left 
ventricle. It increases the safety of the patient while undergoing the procedure and determines the 
CSPOT timing-intervals used for the chronic study. A comparable setup has been used in previous 
MDT studies without any pacing delivery complications (iSPOT study: Clinical Trial Registration: 

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NTC01883141 and SYNSEQ study: Clinical Trial Registration: NTC 02914457). In total 62 patients 
were included with successful protocol execution and data collection. [15] 
Foreseeable or potential adverse events and patient complications associated with the acute use of 
the implanted system the implementation or use of the CSPOT Research System have been 
identified through the hazard analysis. The hazard analysis is composed of a review of previous MDT 
studies and literature to compile the estimation of harm for the foreseeable adverse events. The 
CSPOT Research System Hazard Analysis Log – D00329642_C. provides an overview of additional 
foreseeable events, mitigations, conservative estimates of incidence rates, hazardous situations, 
derived from adverse event data from previous Medtronic clinical studies and literature around the 
components/use of the CSPOT system. 

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19. 
Version History 
 
Version 
Summary of changes 
Justification of changes 
Potential impact of the change on 
performance, effectiveness, or 
safety or other endpoints 
Identification of the affected study 
documents 
Author(s)/Title 
1.0 
N/A - First Version 
release 
N/A 
N/A 
N/A 
Rachael Rose, Pr 
Clinical Research 
Specialist 
Richard Cornelussen, 
Pr. Scientist 
Robert Stadler, Sr. 
Distinguished 
Scientist 

CSPOT (Conduction System Pacing Optimized 
Therapy) Clinical Investigation Plan 
Form 
Version    4.0, 2-Apr-2022 
Page 87 of 88 
This document is electronically controlled Medtronic Business Restricted  056-F275, vB Clinical Investigation Plan Template 
 
 
 
Version 
Summary of 
changes 
Justification of 
changes 
Potential impact of 
the change on 
performance, 
effectiveness, or 
safety or other 
endpoints 
Identification of the 
affected study 
documents 
Author(s)/Title 
2.0 
Updated language to section 
11.1: 
• 
The protocol procedures 
may take up to 90 minutes 
longer than the standard 
CRT procedure time 
which includes up to 10 
minutes of additional 
fluoroscopy exposure. 
• 
The lead implant 
configurations for this study 
are considered 
investigational and have not 
been studied for MRI use. 
Therefore, the MRI 
conditional labeling will not 
apply for these patients. 
Updates in Section 4.1: 
• 
His Pacing updated to His 
Bundle Pacing 
• 
CV+LV updated to CSP +LV 
Deletion in 10.4 of the language: (or
the subject’s authorized/designated
representative or guardian) 
Table 5: updated Component 
column to reflect Medtronic 
Defibrillation Leads in respect to 
the RV defib leads 
Table 6 (also reflective in section 3 
Synopsis): Implant (occur within 30 
days prior to enrollment) update to 
Implant (occur within 30 days after 
to enrollment) 
• 
Clarification to describe 
in more detail protocol 
procedure time and 
additional risk for lead 
implant configurations 
• 
Grammatical and 
language updates 
needed for consistency. 
N/A 
Master Informed 
Consent 
Template V1 
dated 
8-Mar-2021 
Rachael Rose, Pr 
CRS 
Richard Cornelussen, 
Pr.   Scientist 
Robert Stadler, Sr. 
Distinguished 
Scientist 

CSPOT (Conduction System Pacing Optimized 
Therapy) Clinical Investigation Plan 
Form 
Version    4.0, 2-Apr-2022 
Page 88 of 88 
This document is electronically controlled Medtronic Business Restricted  056-F275, vB Clinical Investigation Plan Template 
 
 
 
Version 
Summary of changes 
Justification of changes 
Potential impact of the change on 
performance, effectiveness, or 
safety or other endpoints 
Identification of the affected study 
documents
Author(s)/Title 
3.0 
• 
Increase number of 
sites from 8 to 12 
• 
Updated language in 
Exclusion criteria to: 
Subject has 
complex or repaired 
congenital heart 
disease 
Allow for the study to 
include more sites if 
needed to meet total 
number of patients within 
the study timeframe 
Updating exclusion criteria 
for better clarification 
N/A 
N/A 
Rachael Rose, Pr 
Clinical Research 
Specialist 
Richard Cornelussen, 
Pr. Scientist 
Robert Stadler, Sr. 
Distinguished 
Scientist 

CSPOT (Conduction System Pacing Optimized 
Therapy) Clinical Investigation Plan 
Form 
Version    4.0, 2-Apr-2022 
Page 89 of 88 
This document is electronically controlled Medtronic Business Restricted  056-F275, vB Clinical Investigation Plan Template 
 
 
4.0 
• 
Updated Secondary 
Objectives to 
measure 
improvement 
relative to baseline 
• 
Update to language 
in Section 10.6.2 and 
Table 7 for final 
device programming 
of the CSPOT 
configuration. 
Updates allow for 
physician discretion 
in final device 
programming and 
allow for the best 
LVcs electrode that 
was used during the 
acute testing to also 
be used for chronic 
programming unless 
phrenic nerve 
stimulation, lead 
dislodgement or 
high capture 
threshold occur 
• 
Updates to methods 
for statistical 
analysis in Section 
14.4 and 14.5 to 
Primary objectives 1 
& 2 as well as 
secondary 
objectives 1, 2, & 5 
 
• 
Aligns with 
method for 
statistical 
analysis 
• 
Adjustment 
created for 
flexibility to 
ensure 
continued 
patient safety 
• 
Aligns more with 
the study 
statistical 
analysis plan  
N/A 
N/A 
Rachael Rose, Pr 
Clinical Research 
Specialist 
Richard Cornelussen, 
Pr. Scientist 
Robert 
Stadler, 
Sr. 
Distinguished 
Scientist 
 
Patrick 
Zimmerman, Pr. 
Statistician