ExtraVascular Implantable Cardioverter Defibrillator (EV ICD) Japan Study
Phase: NA
Conditions: Tachycardia, Ventricular Arrythmia
Sponsor: Medtronic Cardiac Rhythm and Heart Failure

ExtraVascular Implantable Cardioverter Defibrillator (EV ICD) Japan Study 
NCT07091916 
Clinical Investigation Plan, 17-OCT-2022 

EV ICD Japan Study Clinical Investigation Plan 
MDT22010 
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Clinical Investigation Plan 
Clinical Investigation Plan/Study Title 
ExtraVascular Implantable Cardioverter Defibrillator 
(EV ICD) Japan Study 
Clinical Investigation Plan Identifier 
MDT22010 
Study Product Name 
EV ICD System 
Sponsor/Local Sponsor 
Medtronic Japan Co., Ltd. 
1-2-70 Konan, Minato-ku,
Tokyo Japan 108-0075
Shinagawa Season Terrace 22F
Phone: (+81) 3-6774-4611
Fax: (+81) 3-6774-4605
Document Version 
3.0, 17-OCT-2022 
Coordinating Investigator 
Dr. Kengo Kusano 
National Cardiovascular Center Hospital 
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. 
Contact Information and Glossary ................................................................................ 8 
1.1. Study Oversight .................................................................................................................. 8 
1.2. CROs and Core Labs ........................................................................................................... 8 
1.3. Glossary ............................................................................................................................. 9 
2. 
Synopsis ...................................................................................................................... 11 
3. 
Introduction ................................................................................................................ 19 
3.1. Background ...................................................................................................................... 19 
3.2. Purpose ........................................................................................................................... 22 
4. 
Objectives and/or Endpoints ...................................................................................... 22 
4.1. Objectives ........................................................................................................................ 22 
 Primary Objectives .............................................................................................................. 22 
 Ancillary Objectives ............................................................................................................. 23 
5. 
Study Design ............................................................................................................... 23 
5.1. Duration........................................................................................................................... 25 
5.2. Rationale.......................................................................................................................... 25 
5.3. Minimization of Bias .......................................................................................................... 26 
6. 
Product Description..................................................................................................... 27 
6.1. General ............................................................................................................................ 27 
 EV ICD (Model DVEX3E4) .................................................................................................... 28 
 EV ICD Lead (Model EV2401) .............................................................................................. 29 
 Sternal Tunneling tool (Model EAZ101) .............................................................................. 30 
 Transverse Tunneling tool (Model EAZ201) ........................................................................ 31 
 Oscor SafeSheath® II Model SSCL9 ...................................................................................... 31 
 EV ICD Programmer Software (Model SW041), Medtronic CareLink 2090 Programmer   
with Analyzer and Medtronic CareLink Encore 29901 Programmer .................................. 32 
 MyCareLink Patient Monitor (Model 24952) ...................................................................... 32 
6.2. Manufacturer .................................................................................................................... 33 
6.3. Packaging ........................................................................................................................ 33 
6.4. Intended Population ......................................................................................................... 34 

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6.5. Equipment ....................................................................................................................... 34 
6.6. Product Use ..................................................................................................................... 34 
6.7. Product Training Requirements .......................................................................................... 34 
6.8. Product Receipt, Tracking, and Accountability ..................................................................... 35 
6.9. Product Storage ................................................................................................................ 36 
6.10. Product Return ............................................................................................................... 36 
7. 
Selection of Subjects ................................................................................................... 36 
7.1. Study Population .............................................................................................................. 36 
7.2. Subject Enrollment ........................................................................................................... 37 
7.3. Inclusion Criteria .............................................................................................................. 37 
7.4. Exclusion Criteria .............................................................................................................. 37 
8. 
Study Procedures ........................................................................................................ 40 
8.1. Schedule of Events ........................................................................................................... 41 
8.2. Medications ...................................................................................................................... 43 
 Prior and Concomitant Medications ................................................................................... 43 
8.3. Subject Consent ............................................................................................................... 43 
8.4. Enrollment / Baseline ........................................................................................................ 45 
 Subject Pre-implant Anatomy Evaluation ........................................................................... 46 
8.5. Implant Visit ..................................................................................................................... 46 
 Antibiotic and Infection Control Strategies ........................................................................ 46 
 Anticoagulation ................................................................................................................... 46 
 Dual antiplatelet therapy .................................................................................................... 47 
 Fluoroscopy and Photography ............................................................................................ 47 
 Implant Procedure Steps ..................................................................................................... 48 
 Implant Testing – EV ICD System ........................................................................................ 54 
 Induction and Defibrillation Testing ................................................................................... 55 
 Subject Exit for Incomplete Implant Visit ........................................................................... 62 
8.6. Pre-Hospital Discharge ...................................................................................................... 63 
 Sensing Testing.................................................................................................................... 64 
 Impedance Testing .............................................................................................................. 64 
 Pacing Testing ..................................................................................................................... 65 
 Imaging ................................................................................................................................ 65 
8.7. Scheduled Follow-up Visits ................................................................................................ 65 

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 2-Week Follow-up Visit ....................................................................................................... 66 
 3-Month Follow-up Visit ..................................................................................................... 67 
 6-Month Follow-up Visit ..................................................................................................... 67 
 Long-term follow-up Visits .................................................................................................. 68 
 Device Troubleshooting ...................................................................................................... 68 
 Electrical Testing ................................................................................................................. 68 
8.8. Unscheduled Visits ............................................................................................................ 69 
8.9. Images and recordings ..................................................................................................... 69 
8.10. Save-to-Media Files ......................................................................................................... 69 
8.11. CareLink Transmissions ................................................................................................... 70 
8.12. Healthcare Utilizations ..................................................................................................... 70 
8.13. System Modification ........................................................................................................ 70 
8.14. Role of the Sponsor Representatives ................................................................................ 71 
8.15. Assessment of Efficacy .................................................................................................... 71 
8.16. Assessment of Safety ...................................................................................................... 72 
8.17. Recording Data ............................................................................................................... 72 
8.18. Deviation Handling .......................................................................................................... 72 
8.19. Subject Withdrawal or Discontinuation ............................................................................. 73 
9. 
Risks and Benefits ....................................................................................................... 74 
9.1. Potential Risks .................................................................................................................. 74 
9.2. Potential Benefits .............................................................................................................. 80 
9.3. Risk-Benefit Rationale ....................................................................................................... 81 
10. 
Adverse Events and Device Deficiencies .................................................................. 81 
10.1. Assessment .................................................................................................................... 82 
 Adverse Events Assessment .............................................................................................. 82 
 Device Deficiencies Assessment ....................................................................................... 82 
10.2. Processing Updates and Resolution .................................................................................. 83 
10.3. Adverse Events and Device Deficiency Definitions ............................................................. 83 
10.4. Adverse Event and Deficiency Classification ...................................................................... 90 
10.5. Reporting of Adverse Events ............................................................................................ 92 
10.6. Subject Death ................................................................................................................. 94 
10.7. Death Classification and Reporting ................................................................................... 94 
10.8. Product Complaint Reporting ........................................................................................... 95 

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11. 
Data Review Committees ......................................................................................... 95 
11.1. Clinical Events Committee ............................................................................................... 95 
11.2. Episode Review Committee ............................................................................................. 96 
12. 
Statistical Design and Methods ................................................................................ 96 
12.1. General Considerations ................................................................................................... 96 
12.2. Sample Size .................................................................................................................... 97 
12.3. Primary Objective #1: Safety ........................................................................................... 97 
 Hypothesis ......................................................................................................................... 97 
 Performance Requirements .............................................................................................. 97 
 Rationale for Performance Criteria ................................................................................... 98 
 Analysis Methods .............................................................................................................. 98 
 Determination of Subjects/Data for Analysis ................................................................... 98 
12.4. Primary Objective #2: Efficacy ......................................................................................... 98 
 Hypothesis ......................................................................................................................... 98 
 Performance Requirements .............................................................................................. 98 
 Rationale for Performance Criteria ................................................................................... 99 
 Analysis Methods .............................................................................................................. 99 
 Determination of Subjects/Data for Analysis ................................................................... 99 
12.5. Ancillary Objective #1 ..................................................................................................... 99 
 Hypothesis ......................................................................................................................... 99 
 Performance Requirements .............................................................................................. 99 
 Rationale for Performance Criteria ................................................................................... 99 
 Analysis Methods ............................................................................................................ 100 
 Determination of Subjects/Data for Analysis ................................................................. 100 
12.6. Ancillary Objective #2 ....................................................................................................100 
 Hypothesis ....................................................................................................................... 100 
 Performance Requirements ............................................................................................ 100 
 Rationale for Performance Criteria ................................................................................. 100 
 Analysis Methods ............................................................................................................ 101 
 Determination of Subjects/Data for Analysis ................................................................. 101 
12.7. Ancillary Objective #3 ....................................................................................................101 
 Hypothesis ....................................................................................................................... 101 

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 Performance Requirements ............................................................................................ 101 
 Rationale for Performance Criteria ................................................................................. 101 
 Analysis Methods ............................................................................................................ 101 
 Determination of Subjects/Data for Analysis ................................................................. 102 
12.8. Ancillary Objective #4 ....................................................................................................102 
 Hypothesis ....................................................................................................................... 102 
 Performance Requirements ............................................................................................ 102 
 Rationale for Performance Criteria ................................................................................. 102 
 Analysis Methods ............................................................................................................ 102 
 Determination of Subjects/Data for Analysis ................................................................. 102 
12.9. Ancillary Objective #5 ....................................................................................................102 
 Hypothesis ....................................................................................................................... 103 
 Performance Requirements ............................................................................................ 103 
 Rationale for Performance Criteria ................................................................................. 103 
 Analysis Methods ............................................................................................................ 103 
 Determination of Subjects/Data for Analysis ................................................................. 103 
12.10. Ancillary Objective #6 ..................................................................................................103 
 Hypothesis..................................................................................................................... 104 
 Performance Requirements .......................................................................................... 104 
 Rationale for Performance Criteria ............................................................................... 104 
 Analysis Methods .......................................................................................................... 104 
 Determination of Subjects/Data for Analysis ............................................................... 104 
12.11. Ancillary Objective #7 ..................................................................................................104 
 Hypothesis..................................................................................................................... 104 
 Performance Requirements .......................................................................................... 105 
 Rationale for Performance Criteria ............................................................................... 105 
 Analysis Methods .......................................................................................................... 105 
 Determination of Subjects/Data for Analysis ............................................................... 105 
12.12. Supplemental Analysis ..................................................................................................105 
13. 
Ethics ...................................................................................................................... 105 
13.1. Statement(s) of Compliance ...........................................................................................105 
14. 
Study Administration .............................................................................................. 107 

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14.1. Monitoring .....................................................................................................................107 
14.2. Data Management .........................................................................................................108 
14.3. Direct Access to Source Data/Documents ........................................................................109 
14.4. Confidentiality ...............................................................................................................109 
14.5. Liability .........................................................................................................................109 
14.6. CIP Amendments ...........................................................................................................109 
14.7. Required Records and Reports ........................................................................................110 
 Investigator Records ....................................................................................................... 110 
 Investigator Reports ........................................................................................................ 111 
 Sponsor Records ............................................................................................................. 112 
 Sponsor Reports .............................................................................................................. 113 
14.8. Suspension or Early Termination .....................................................................................115 
 Study-wide Suspension or Early Termination ................................................................. 115 
 Investigator/Site Suspension or Early Termination ........................................................ 115 
 Procedures for Suspension or Early Termination ........................................................... 116 
15. 
References .............................................................................................................. 118 
16. 
Appendices ............................................................................................................. 121 
Appendix A: Draft Data Collection Elements (Case Report Forms) ...................................... 122 
Appendix B: Instructions for Use ....................................................................................... 123 
Appendix C: Informed Consent Templates ......................................................................... 124 
Appendix D: Foreseeable Adverse Event List ..................................................................... 125 
Appendix E: Participating Investigators and Institutions ..................................................... 136 
Appendix F: Ethics Committee and Competent Authority List ............................................. 137 
Appendix G: Previous Clinical Investigations ..................................................................... 138 
Appendix H: Chronic Defibrillation Testing Protocol ........................................................... 139 
Appendix I: Investigator Statement ..................................................................................... 141 
17. 
Version History ....................................................................................................... 141 
 

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1. Contact Information and Glossary 
1.1. Study Oversight 
The Coordinating Investigator will support the execution of the EV ICD Japan study and provide 
guidance, feedback and direction to the study. 
1.2. CROs and Core Labs 
No CROs and core labs will be used in this study. 
 
 

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1.3. Glossary 
Term 
Definition 
AE 
Adverse Event 
ADE 
Adverse Device Effect 
AP 
Anterior-Posterior  
ATP 
Antitachycardia Pacing 
BMI 
Body Mass Index 
CEC 
Clinical Events Committee 
CIP 
Clinical Investigation Plan 
CFR 
(US) Code of Federal Regulations 
DD 
Device Deficiency 
Ethics 
Committee 
Term that will be used collectively in reference to an Institutional Review Board (IRB)/Medical 
Ethics Committee (MEC)/Human Research Ethics Committee (HREC)/Research Ethics Board 
(REB)/Head of Medical Institution (HOMI) unless otherwise stated 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EGM 
Electrogram 
EP 
Electrophysiologist/Electrophysiology 
ERC 
Episode Review Committee 
EV ICD 
Extravascular Implantable Cardioverter Defibrillator 
FDA 
(US) Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act 
GCP 
Good Clinical Practice 
HCU 
Health Care Utilization 
HOMI 
Head of Medical Institution 
ICD 
Implantable Cardioverter Defibrillator 
ID 
Identification 
IFU 
Instructions for Use 
IRB 
Institutional Review Board 
ISF 
Investigator Site File 
LAT 
Lateral 
NOAC 
Novel Oral Anticoagulant 
PA 
Posterior-Anterior  
PHD 
Pre-Hospital Discharge  
OPC 
Objective Performance Criterion 
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Device Effect 
SF-12 
Short Form, 12-question (Quality of Life Survey) 
SSVA 
Sustained Shockable Ventricular Arrhythmia  
TEE 
Transesophageal Echocardiogram 
TV 
Transvenous 
US 
United States of America 
USADE 
Unanticipated Serious Adverse Device Effect 
VF 
Ventricular Fibrillation 

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Term 
Definition 
VT 
Ventricular Tachycardia 
Zone 1 
Tunnelling and deployment of the lead in the substernal space 
Zone 2 
Tunnelling of the lead from the sternum to the device pocket 
 
 
 

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2. Synopsis 
Title 
Extravascular Implantable Cardioverter Defibrillator (EV ICD) 
Japan Study 
Clinical Study Type 
Prospective, multi-center, single-arm, non-randomized, pre-
market clinical study  
Product Name and Status 
Investigational System Components: 
• 
Medtronic Model DVEX3E4 EV ICD 
• 
Medtronic Model EV2401 EV ICD Lead 
 
Investigational Accessory Components: 
• 
Medtronic Model EAZ101 Sternal Tunneling Tool 
• 
Medtronic Model EAZ201 Transverse Tunneling Tool 
• 
Oscor SafeSheath® II, model number SSCL9 introducer  
• 
EV ICD SW041 Programmer Software Version 8.3.1 (or 
greater) 
• 
MyCareLink Patient Monitor Model 24952 (may 
become available during the course of the study) 
 
Market Released Components: 
• 
Medtronic 2090 CareLink Programmer with analyzer 
(or CareLink Encore 29901 Programmer)  
Sponsor  
Medtronic Japan Co., Ltd. 
1-2-70 Konan, Minato-ku, 
Tokyo Japan 108-0075 
Shinagawa Season Terrace 22F 
Phone: +81 3 6774 4611 
Indication under investigation  
The Medtronic EV ICD System (defibrillator and lead) is 
indicated for the automated treatment of patients who 
have experienced, or are at significant risk of developing, 
life-threatening ventricular tachyarrhythmias.   
Investigation Purpose 
The main purpose of the EV ICD Japan study is to 
characterize acute safety and performance of the EV ICD 
System for Japanese patients. 
Primary Objective(s) 
Primary Safety Objective:  Characterize the freedom from 
major complications related to the EV ICD System and/or 
procedure at 2 weeks post-implant. 

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The endpoint is defined as a subject’s first occurrence of a 
major complication related to the EV ICD System and/or 
procedure, as determined by an independent Clinical Events 
Committee (CEC), that occurs on or prior to 2 weeks (14 
days) post-implant. 
 
Primary Efficacy Objective: Characterize the EV ICD 
defibrillation testing success rate at implant. 
 
The endpoint, defibrillation testing success, is defined as: 
• 
Single SSVA conversion at 20J, or  
• 
Conversion of two successive episodes of SSVA at 30J in 
final system configuration. 
Ancillary Objective(s) 
• 
Characterize appropriate and inappropriate shocks  
• 
Characterize electrical performance (pacing capture 
thresholds, pacing impedance, sensing amplitudes) 
over time  
• 
Characterize extracardiac pacing sensation 
• 
Characterize asystole pacing 
• 
Summarize ATP performance with spontaneous 
arrhythmias 
• 
Summarize adverse events 
• 
Characterize EV ICD chronic defibrillation conducted 
per physician discretion 
Sample Size 
Up to 25 enrollments at up to 3 sites in Japan, to allow 
about 15 subjects to, in the case of the safety objective, 
undergo an implant attempt of the EV ICD System, and in 
the case of the efficacy objective, complete the pre-
specified defibrillation testing protocol.  
 
Maximum number of subjects enrolled at each site will be 
capped at 12, which is approximately 50% of the total 
number of subjects enrolled. 

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Inclusion/Exclusion Criteria 
Inclusion Criteria 
1. Patient has a Class I or IIa indication for implantation of 
an ICD according to the ACC/AHA/HRS Guidelinesi, or 
ESC guidelinesii. 
2. Patient is at least 18 years of age and meets age 
requirements per local law. 
3. Patient is geographically stable and willing and able to 
complete the study procedures and visits for the 
duration of the follow-up. 
Exclusion Criteria 
1. Patient is unwilling or unable to personally provide 
Informed Consent. 
2. Patient has indications for bradycardia pacing iii or 
Cardiac Resynchronization Therapy (CRT) iv (Class I, IIa, 
or IIb indication). 
3. Patient with an existing pacemaker, ICD, or CRT device 
implant or leads. 
4. Patients with these medical interventions are excluded 
from participation in the study: 
• 
Prior sternotomy 
• 
Any prior medical condition or procedure that leads 
to adhesions in the anterior mediastinal space (i.e., 
prior mediastinal instrumentation, mediastinitis) 
• 
Prior abdominal surgery in the epigastric region 
• 
Planned sternotomy 
• 
Prior chest radiotherapy 
Or any other prior/planned medical intervention not 
listed that precludes their participation in the opinion of 
the Investigator. 
5. Patient has previous pericarditis that: 
• 
Was chronic and recurrent, or  
• 
Resulted in pericardial effusion v, or 
• 
Resulted in pericardial thickening or calcification. vi 
6. Patients with these medical conditions or anatomies are 
excluded from participation in the study: 
• 
Hiatal hernia that distorts mediastinal anatomy 

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i Al-Khatib SM, Stevenson WG, Ackerman MJ, Bryant WJ, Callans DJ, Curtis AB, Deal BJ, Dickfeld T, Field ME, Fonarow GC, 
Gillis AM, Hlatky MA, Granger CB, Hammill SC, Joglar JA, Kay GN, Matlock DD, Myerburg RJ, Page RL. 2017 AHA/ACC/HRS 
guideline for management of patients with ventricular arrhythmias. 
ii Priori SG, Blomstrom-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, Elliot PM, Fitzsimons D, Hatala R, Hindricks 
G, Kirchhof P, Kjeldsen K, Kuck KH, Hernandez-Madrid A, Nikolaou N, Norekval TM, Spaulding C, Van Veldhuisen DJ. 2015 
ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. 
European Heart Journal 2015 36:41 (2793-2867). https://doi.org/10.1093/eurheartj/ehv316 
iii 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator 
programming and testing). 
iv ACC/AHA/HRS guidelines for Cardiac Resynchronization Therapy 
v As documented on echo or MRI 
vi As documented on CT scan or MRI  

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• 
Marked sternal abnormality (e.g., pectus 
excavatum) 
• 
Decompensated heart failure 
• 
COPD with oxygen dependence 
• 
Gross hepatosplenomegaly 
Or any other known medical condition or anatomy type 
not listed that precludes their participation in the 
opinion of the Investigator. 
7. Patients with a medical condition that precludes them 
from undergoing defibrillation testing:  
• 
Severe aortic stenosis 
• 
Intracardiac LA or LV thrombus 
• 
Severe proximal three-vessel or left main coronary 
artery disease without revascularization 
• 
Hemodynamic instability 
• 
Unstable angina 
• 
Recent stroke or transient ischemic attack (within 
the last 6 months) 
• 
Known inadequate external defibrillation 
• 
LVEF <20% 
• 
LVEDD >70 mm 
Or any other known medical condition not listed that 
precludes their participation in the opinion of the 
Investigator. 
8. Patient with any evidence of active infection or 
undergoing treatment for an infection. 
9. Patient is contraindicated from temporary suspension 
of oral/systemic anticoagulation   
10. Patient with current implantation of neurostimulator or 
any other chronically implanted device that delivers 
current in the body. 
11. Patient meets ACC/AHA/HRS or ESC clinical guideline 
Class III criteria for an ICD (e.g., life expectancy of less 
than 12 months). 
12. Patient is enrolled or planning to enroll in a concurrent 
clinical study that may confound the results of this 

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study, without documented pre-approval from a 
Medtronic study manager. 
13. Patient with any exclusion criteria as required by local 
law (e.g., age or other). 
14. Pregnant women or breastfeeding women, or women 
of child bearing potential and who are not on a reliable 
form of birth regulation method or abstinence. vii 
Study Procedures and Assessments 
Subjects indicated for single-chamber ICD therapy will be 
recruited and implanted with the Medtronic EV ICD System. 
Once enrolled, a subject will be assessed at the following 
visits: 
• 
Baseline  
• 
Implant  
• 
Pre-Hospital Discharge (PHD) 
• 
2 Weeks (2WK) 
• 
3 Months (3M) 
• 
6 Months (6M) 
• 
Long-term: Every 6 months thereafter until study 
closure (12, 18, 24… Months) 
• 
Unscheduled (as they occur) 
• 
System Modifications (as they occur) 
• 
Defibrillation testing (when conducted per physician 
discretion) 
• 
Exit 
 
Study procedures are outlined in the table below. 
 
Study procedure 
Baseline 
Implant 
PHD 
2WK 
3M 
6M 
Long 
Term 
Unscheduled 
Sys 
Mod 
Exit 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Assessment 
X 
 
 
 
 
 
 
 
 
 
Physical Exam, Demographics, 
Cardiovascular Medical History, 
Surgical History 
X 
 
 
 
 
 
 
 
 
 
SF-12 quality of life survey 
X 
 
 
 
 
X 
 
 
 
 
System and procedure 
information 
 
X 
 
 
 
 
 
 
X 
 
 
vii Women of child-bearing potential must undergo a pregnancy test within seven days prior to EV ICD Japan 
Study procedure 

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Pre-procedure Transesophageal 
Echocardiogram (TEE)1 
 
X1 
 
 
 
 
 
 
 
 
CT-Scan or MRI 
X2 
 
 
 
 
 
 
 
 
 
Fluoroscopy recordings during 
tunneling procedure 
 
X 
 
 
 
 
 
 
X4 
 
Fluoroscopy (AP and Lateral 
cine) of final ICD generator and 
lead position 
 
X 
 
 
 
 
 
 
X4 
 
Sensing, Impedance, & Pacing 
tests 
 
X 
X 
X 
X 
X 
X 
X3 
X4 
 
Defibrillation testing 
 
X 
 
 
 
 
 
 
X4 
 
Chest Radiographs (PA/Lateral) 
X 
 
X 
 
 
 
 
 
 
 
Echocardiographic data within 
the last 6 months 
X 
 
 
 
 
 
 
 
 
 
Save-to-media files 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medications (for subjects 
implanted with any device) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events5 (including AEs 
with fatal outcome), Device 
Deficiencies, HCUs, Study 
Deviations, and Other cardiac 
imaging 
As they occur 
1 Required for subjects presenting in atrial fibrillation to confirm the absence of LA or LV thrombus.  
2Taken within the last year. Recommended for first 3 subjects at minimum, for each implanter. If collected/reviewed, send CT-scan 
and/or MRI to Medtronic. 
3 Optional. If electrical testing conducted, print the Testing Reports to PDF or paper and send a copy of the reports to Medtronic. 
4 System modification where a subject leaves the procedure with an EV ICD System. 
5 Recommended to collect incision photographs if an infection related to the EV ICD System is suspected. 
Safety Assessments 
All Adverse Events that occur from the time of enrollment 
through study exit will be collected and reported to 
Medtronic and regulatory agencies (per local requirement) 
during the study. Additionally, any device deficiency related 
to the EV ICD System or accessory will be collected.   
 Statistics 
The efficacy primary objective of EV ICD defibrillation 
testing success rate at implant will be characterized using a 
proportion. To evaluate the safety primary objective, the 2-
week EV ICD System/procedure major complication-free 
rate will be calculated using the Kaplan-Meier method. 
Descriptive statistics will be used to summarize remaining 
endpoints. For some endpoints such as pacing testing, 
multiple measurements per subject will be assessed. 
Once all subjects with an implant attempt have completed 
the 2-week follow-up visit, all primary and ancillary 

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objectives will be analyzed and a clinical study report will be 
developed. 
 
 
 

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3. Introduction  
3.1. Background  
Today, implantable cardioverter-defibrillator (ICD) therapy is the treatment of choice for patients 
who are at risk for sudden cardiac death due to life-threatening ventricular arrhythmias. Traditional 
ICD systems with transvenous leads are considered standard of care for primary or secondary 
prevention of tachyarrhythmic death. However, these systems have limitations. Short- and long-
term complications arising from ICD systems with transvenous leads, such as infection, 
pneumothorax, venous thrombosis, lead dislodgement, lead malfunction, and lead perforation, have 
persisted for decades as impediments to ICD usage1,2,3,4,5. As a result, there is demand for novel ICD 
systems that circumvent the potential disadvantages of transvenous ICD systems by preserving the 
heart and vasculature6,7. 
Non-transvenous ICD systems may represent a means of providing life-saving therapy to patients in 
whom it is not possible or desired to enter the venous system or heart chambers; for example, 
patients with anatomical anomalies, high infection risk, limited vascular access, or juvenile patients 
where the venous anatomy is preferably avoided8,9,10,11.  
Currently, there are non-transvenous subcutaneous and epicardial leads that are used with standard 
ICDs. Cameron Health developed the SQ-RX SubQ ICD system, which was market released in 2009. 
Boston Scientific acquired the Cameron Health device, and market released their Emblem 
Subcutaneous (SubQ) ICD system in 2015. During clinical studies for both of these devices, patients 
were implanted with a non-transvenous ICD system and a subcutaneous lead. Perioperative results 
from the S-ICD post approval study indicated acceptable short-term complication rates12, and first 
year post-implant results from the EFFORTLESS study confirmed the safety demonstrated in the IDE 
S-ICD trial, and indicated performance rates for S-ICD complications, inappropriate shocks, and 
conversion efficacy similar to those observed in transvenous systems13. 
Medtronic has developed an extravascular ICD system which uses a substernal lead rather than a 
transvenous or a subcutaneous lead. The EV ICD System has similar capabilities to a single-chamber 
transvenous system while avoiding leads in the heart or vasculature. Compared to current market-
released non-transvenous subcutaneous ICDs, the EV ICD System includes a smaller device that uses 
less defibrillation energy, which may result in longer battery life and has the additional capabilities to 
deliver pacing therapies such as ATP and backup asystole pacing from a single device. 
Previously published case studies indicate defibrillation from non-endocardial locations is possible 
and shock energies similar to those of transvenous devices can successfully defibrillate if the 
defibrillation coil is placed in an epicardial or mediastinal location8,9,10,14,15,16,17,18,19,20. The EV ICD 
System is of similar size and energy outputs as current transvenous systems (e.g., approximately 
33cc and 40 Joules).  

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The first human experience of acute and chronic defibrillation lead placement in the substernal 
extra-cardiac space was reported by Tung et al. in 2007 using a minimally invasive approach via the 
manubrium10. In three patients (two patients having ipsilateral venous occlusion and one patient 
wishing to avoid additional transvenous hardware placement), either a Medtronic Model 6996SQ or 
Model 6937 coil was tunneled to the substernal extra-cardiac space anterior to the right ventricle 
(RV). All implants were successful without complication. Ventricular Fibrillation (VF) was induced 
with T-wave shock. In each patient, the safety margin was determined to be at least 10 Joules (J) by 
two successful VF terminations. 
Later, Guenther et al. reported the results of failed subcutaneous defibrillation lead implantation in 
one human patient for whom defibrillation threshold testing (DFT) at 65 Joules and 80 Joules failed 
to terminate VF six times17. As a result of failed subcutaneous DFT, the lead was instead positioned 
substernally using an 11-French peel-away insertion sheath and the tunneling tool of the 
manufacturer. After making a small incision at the xiphoid process, fluoroscopy and “direct bone 
contact” were used to guide lead placement. Substernal DFT was successful and substernal sensing 
quality was acceptable. There were no complications, including no damage to the pericardium. The 
patient reported no chronic pain and there were no other findings at follow-up of four weeks. 
Guenther et al. concluded that “substernal lead positioning is easy to achieve” and provides an 
effective means of extravascular lead implantation17. 
In order to develop and evaluate a newly designed system for the substernal space, Medtronic 
completed pre-clinical research evaluations of substernal defibrillation, pacing, and sensing, and 
subsequently initiated three acute human clinical research feasibility studies with combined 121 
implants to explore the potential development of a future chronic implantable extravascular 
defibrillation system with a lead implanted in the substernal space. Both pre-clinical and clinical data 
are described in further detail within the Investigator’s Brochure. 
The first human clinical feasibility study, Acute Substernal Defibrillation (ASD), showed substernal 
defibrillation is feasible with energy available in current transvenous ICDs, with defibrillation 
successful in 13 of 14 subjects (93%) at 35J (95% CI: 74.7% - 99.8%). One failure was associated with 
high and lateral shock coil placement21. The second human clinical feasibility study, Substernal 
Pacing Acute Clinical Evaluation (SPACE), in which 26 subjects underwent pacing evaluation, showed 
that pacing is possible in nearly all patients from the extravascular substernal location22. The third 
human clinical feasibility study, Acute Extravascular Defibrillation, Pacing and Electrogram (ASD2), 
was designed to further assess study pacing thresholds and defibrillation efficacy via substernal 
therapy delivery in a larger cohort as well as collect additional data, mainly multi-vector substernal 
electrograms during induced VF/VT and intrinsic rhythms directly from an investigational lead placed 
in the substernal space. The substernal lead was implanted in 79 patients, with a median 
implantation time of 12.0 ± 9.0 min. Ventricular pacing was successful in at least 1 vector in 76 of 78 
patients (97.4%), and 72 of 78 (92.3%) patients had capture in ≥1 vector with no extracardiac 
stimulation. A 30-J shock successfully terminated 104 of 128 episodes (81.3%) of ventricular 

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fibrillation in 69 patients. The ASD2 study demonstrated the ability to pace, sense, and defibrillate 
using a lead designed specifically for the substernal space23. 
Acute feasibility data from 121 patients provided assurance to initiate a pilot study with first-in-
human chronic device implant of the EV ICD System. The main benefits of conducting a pilot study 
included (1) facilitating optimization of device settings, (2) providing additional recommendations 
and best practices during the implant procedure, and (3) providing an avenue for more robust data 
collection leading up to a pivotal trial. A pilot study was initiated to allow for characterization of the 
EV ICD System in a limited number of subjects before launching into large-scale, global, pivotal 
study. 
The EV ICD Pilot Study was a prospective, non-randomized, chronic first-in-human study conducted 
in four sites in Australia and New Zealand. In this pilot study, 21 patients underwent the EV ICD 
implant procedure. Patients were evaluated at implant, two weeks, four to six weeks, and three 
months after device implant, and continue to be followed. Study investigators characterized the 
safety of the system and implant procedure, defibrillation effectiveness, and sensing and pacing. At 
the time of implant, defibrillation testing was completed on 20 patients. The system successfully 
terminated induced ventricular arrhythmias in 18 patients (90.0%), which is consistent with prior 
clinical studies of existing ICDs24,25. Pacing capture was achieved in more than 95% of study patients. 
One patient experienced ventricular tachycardia outside the hospital setting, which was successfully 
detected and treated by the EV ICD system. This first-in-human chronic study demonstrated that the 
EV ICD system can be implanted with no major complications, and can sense, pace and defibrillate 
the heart26.   
The acute feasibility and pilot studies contributed to the advancement of the EV ICD program, 
including refinement of the device, algorithm and implant procedure. The EV ICD Pivotal Study27 is a 
global prospective, multi-center, single-arm, non-randomized, pre-market clinical study. Patients 
were followed at baseline, implant, PHD, 2 weeks, 3 months, 6 months, and every 6 months 
thereafter. The EV ICD Pivotal study began enrolling in 2019 and completed enrollments in 2021. In 
the EV ICD Pivotal Study, 356 patients were enrolled, and 316 subjects underwent the EV ICD 
implant procedure. Results of this study showed both primary endpoints were met; the defibrillation 
testing success rate at implant was 98.7% and the freedom from major complications related to the 
system and/or procedure at 6 months post-implant was 92.6%28. At the time of this protocol being 
written, patients are still in follow-up and the study is undergoing regulatory review. 
Japan was scheduled to participate in the EV ICD Pivotal Study; however, travel and quarantine 
restrictions due to the Coronavirus Pandemic prevented the study physicians from undergoing the 
required hands-on training program, and eventually Japan could not enroll any subjects. Novelty of 
the EV ICD System and its procedure is high, and it would be meaningful to evaluate its acute 
characteristics and characterize safety under the Japanese medical environment prior to its market 
approval. Based on this above background, this EV ICD Japan limited study has been planned to 
characterize the acute safety and performance of the EV ICD System in a similar patient population 

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without changing the selection and exclusion criteria from the EV ICD Pivotal study and limited the 
region where the trial will be conducted to Japan.   
3.2. Purpose 
The purpose of the clinical study is to characterize the acute safety and performance of the EV ICD 
System for Japanese patients: a complete single-chamber extravascular ICD system with the lead 
implanted substernally.    
4. Objectives and/or Endpoints 
4.1. Objectives 
 Primary Objectives  
The first primary objective is to characterize the freedom from major complications related to the EV 
ICD System and/or procedure at 2 weeks post-implant. The endpoint is defined as a subject’s first 
occurrence of a major complication related to the EV ICD System and/or procedure, as determined 
by an independent Clinical Events Committee (CEC), that occurs on or prior to 2 weeks (14 days) 
post-implant.  
For an adverse event to meet the endpoint, the event must have occurred within 14 days (inclusive) 
of the EV ICD System implant and be adjudicated by the CEC as being a major complication related 
(causal relationship) to the EV ICD System and/or procedure. Major complications are those 
complications resulting in: 
• 
Death 
• 
Permanent loss of defibrillation function (specifically shock) due to mechanical or electrical 
dysfunction of the device  
• 
Hospitalization 
• 
Prolongation of an existing hospitalization by at least 48 hours 
• 
System revision (reposition, replacement, explant) 
The second primary objective is to characterize the defibrillation efficacy at implant of the EV ICD 
System. The endpoint, defibrillation testing success, is defined as: 
• 
Single sustained shockable ventricular arrhythmia (SSVA) conversion at 20J, or  
• 
Conversion of two consecutive episodes of SSVA at 30J in final system configuration. 
Notes: 
• 
In one of the two consecutive SSVA episodes, up to two 30J shocks are permitted. 
• 
To achieve final system configuration, changing the position of the ICD generator and/or the 
lead, or changing shock polarity is permitted. 

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• 
Subjects can return for testing on another day if testing is not fully completed on the day of 
implant. 
• 
If SSVA cannot be induced, the EV ICD System must be removed (refer to section 8.5.8). 
• 
For more information on the rationale behind these objectives, refer to section 12. 
 Ancillary Objectives  
• 
Characterize appropriate and inappropriate shocks  
• 
Characterize electrical performance (pacing capture thresholds, pacing impedance, sensing 
amplitudes) over time  
• 
Characterize extracardiac pacing sensation 
• 
Characterize asystole pacing 
• 
Summarize ATP performance with spontaneous arrhythmias 
• 
Summarize adverse events 
• 
Characterize EV ICD defibrillation testing conducted per physician discretion 
5. Study Design  
The EV ICD Japan Study is a prospective, multi-center, single-arm, non-randomized, pre-market 
clinical study. Enrollment will include about 15 and up to 25 subjects at up to 3 sites in Japan.  
Participating sites that enroll faster than others will be allowed to do so to maintain an adequate 
enrollment rate. However, to ensure a reasonable distribution of experience and minimize site bias 
in study results, the maximum number of subjects enrolled at each site will be capped at 12 
(approximately 50% of 15 total enrollments). 

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Figure 1: Overview of the EV ICD Japan Study  
 

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5.1. Duration 
The expected study duration is approximately 1.5 years from the study’s first enrollment. The 
enrollment period is expected to take approximately 5 months. Individual subjects may be 
participating in the study for a period of minimum 1.5 to approximately 2.5 years. The duration of 
individual subject participation will vary based on timing of site activation, timing of enrollment and 
enrollment rate. Subjects will undergo assessments at Baseline, Pre-Hospital Discharge, 2 Weeks, 3 
Months, 6 Months, and every 6 months thereafter until official study closure. Official study closure is 
defined as when Medtronic and/or Ministry of Health, Labour, and Welfare requirements have been 
satisfied per the CIP and/or by a decision by Medtronic or regulatory authority to stop or close the 
study. Official study closure is expected to occur after the EV ICD System is approved by the MHLW, 
anticipated in 2024.  
5.2. Rationale  
The main purpose of the EV ICD Pivotal Study is to characterize the acute safety and performance of 
the EV ICD System for Japanese patients.  
Prior to this study, three acute human feasibility studies were performed: 
• 
The ASD study demonstrated that substernal defibrillation is feasible with energy available in 
current transvenous (TV)-ICDs21 
• 
The SPACE study demonstrated that pacing is possible in nearly all patients with detection 
comparable to TV-ICD22 
• 
The ASD2 study demonstrated that pacing, sensing, and defibrillation is feasible with a lead 
designed specifically for the substernal space23 
EV ICD device features were designed and developed using data collected from these studies and 
supplemented with animal and bench evaluations.  
In addition to the acute feasibility studies, the EV ICD Pilot study was initiated to allow for chronic 
characterization of the EV ICD System in a limited number of subjects before launching into a large-
scale, global, pivotal study. At this time, the EV ICD Pilot study long-term follow-up is ongoing, and 
will continue through the duration of the EV ICD Pivotal Study in order to continue collecting long-
term follow-up data.  
The EV ICD Pivotal study began enrolling in 2019 and completed enrollments in 2021; patient follow-
up is currently ongoing at the time of this protocol being written. Japan was scheduled to participate 
in the EV ICD Pivotal Study; however, travel and quarantine restrictions due to the Coronavirus 
Pandemic prevented the study physicians from undergoing the required hands-on training program, 
and eventually Japan couldn’t enroll any subjects. Novelty of the EV ICD System and its procedure is 
high, and it would be meaningful to evaluate its acute characteristics and characterize safety under 
the Japanese medical environment prior to its market approval. Based on this above background, we 
have planned this EV ICD Japan limited study to characterize the acute safety and performance of 

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the EV ICD System in an equivalent patient population without changing the selection and exclusion 
criteria from the EV ICD Pivotal study and limited the region where the trial will be conducted to 
Japan. 
5.3. Minimization of Bias 
Selection of subjects, treatment of subjects, and evaluation of study data are potential sources of 
bias. Methods incorporated in the study design to minimize potential bias include (but are not 
limited to): 
• 
Subject demographics and comorbidities will be collected at baseline to later assess 
possible characteristics that may influence endpoints 
• 
Data collection requirements and study procedures will be standardized across all 
geographies 
• 
To ensure a reasonable distribution of data among sites, the maximum number of 
enrollments per site will be 12 subjects. Additionally, sites will be encouraged to enroll at 
least 3 subjects.  
• 
A statistical analysis plan will be developed prior to analyzing data which will document all 
pre-specified analyses and analysis methods 
• 
All study clinicians will be trained on and required to follow the CIP 
• 
All study clinicians and Medtronic personnel will be trained on their respective aspects of 
the study using standardized training materials 
• 
An independent Clinical Events Committee (CEC) will be utilized to regularly review and 
adjudicate reported adverse events 
• 
An Episode Review Committee (ERC) containing independent reviewers will be utilized to 
review and adjudicate device-treated episodes to determine appropriateness of therapy 
(shocks and ATP) delivered to subjects 
• 
All sites will use the same version of the CIP and standardized case report forms when 
possible 
• 
Monitoring visits will be conducted to verify adherence to the CIP and source data. 
In summary, potential sources of bias that may be encountered in this clinical study have been 
considered and minimized by careful study design. 
 
 

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6. Product Description 
6.1. General 
The EV ICD System consists of market-released and investigational components. In this study, the 
devices listed in Table 1 are defined as “The Devices used for clinical study”. 
 Table 1: EV ICD System Components 
Model 
Number 
Component 
Investigational or Commercially 
Available at study start 
System Components 
DVEX3E4 
Extravascular Implantable Cardioverter 
Defibrillator (EV ICD) 
Investigational 
EV2401 
Extravascular quadripolar lead with shaped 
passive fixation 
Investigational 
Accessory Components 
EAZ101 
Sternal Tunneling Tool 
Investigational 
EAZ201 
Transverse Tunneling Tool  
Investigational 
SSCL9 
Oscor SafeSheath® II Hemostatic Tear-away 
Introducer System with Infusion Side Port 
Investigational 
SW041 
Medtronic EV ICD SW041 Programmer 
Software Version 8.3.1 or greater 
Investigational 
2090 
 
or 
29901 
Medtronic CareLink Programmer with 
analyzer  
or 
Medtronic CareLink Encore Programmer 
Commercially available  
Investigational EV ICD SW041 
software is downloaded onto 
programmer, and programmer is 
subsequently labeled as 
containing investigational 
software  
24952 
Medtronic MyCareLink Patient Monitor  
Commercially available, but 
investigational when used with 
EV ICD 
 
The CIP permits up to 25 enrollments to allow about 15 subjects undergoing system implant and 
defibrillation testing to be included in the study. Under the assumption that one system is used per 
subject, as well as a 20% increase to account for system revisions, dropped product, etc., it is 
expected that up to approximately 30 of the following investigational devices may be used during 
the trial: EV ICD, lead, sternal tunneling tool, transverse tunneling tool, introducer, and MyCareLink 
monitor. Each site (up to 3 sites) will have access to at least one programmer with software.  

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  EV ICD (Model DVEX3E4) 
The Medtronic Model DVEX3E4 is an investigational single-chamber, MR-conditional, extravascular 
implantable cardioverter defibrillator (EV ICD). It consists of a titanium generator and a connector 
port housing made from polyurethane and silicone rubber. This multiprogrammable cardiac device 
monitors and regulates the subject’s heart rate. It provides asystole detection and therapy (Pause 
Prevention), ventricular tachyarrhythmia detection and therapy including ATP, and post-shock 
pacing. The EV ICD also provides diagnostic and monitoring features to assist with system evaluation 
and patient care.  
 
Figure 2: The Medtronic EV ICD Model DVEX3E4 
The DVEX3E4 EV ICD contains an EV4 connector, which is compatible with an EV4-LLHH quadripolar 
lead. 
 

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  EV ICD Lead (Model EV2401) 
The Medtronic Model EV2401 extravascular lead is an investigational, pre-shaped, MR-conditional 
lead with passive fixation, designed for sensing, cardioversion, defibrillation and pacing therapies. 
The lead is 8.7 Fr and available in both 52 cm or 63 cm lengths. The body of the lead is made from 
polyurethane, with ring electrodes made from titanium nitride coated platinum iridium, and coil 
electrodes from platinum iridium and tantalum. The lead has two ring electrodes and two coil 
electrodes: Ring 2 (proximal ring), Coil 2 (proximal coil), Ring 1 (distal ring), Coil 1 (distal coil). The 
configuration of these electrodes is shown in Figure 3. The lead has the ability to pace and sense 
between the ring and coil electrodes. In addition, the Coil 1 and Coil 2 electrodes deliver 
cardioversion and defibrillation therapy. 
 
Figure 3: The EV2401 lead 
The proximal end of the lead features an EV4-LLHH quadripolar connector, which is compatible with 
an EV4 connector on an EV ICD.  
 

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  Sternal Tunneling tool (Model EAZ101)  
The Medtronic Model EAZ101 sternal tunneling tool is an investigational tool designed to deliver an 
introducer and an extravascular lead into the anterior mediastinum during implant of an 
extravascular implantable device system.  This is referred to as Zone 1 in Table 4: Outline of the 
proposed implant procedure steps. 
The sternal tunneling tool, shown in Figure 4  below, consists of the following components: 
• 
Handle 
• 
tunneling rod that delivers a 
 introducer to the anterior mediastinum. The 
tunneling rod is malleable to accommodate patient anatomy 
• 
External guide that remains above the skin and indicates the distance and direction of the 
tunneling rod. The external guide is hinged and removable to accommodate physician 
preference and patient anatomy 
• 
Thumb tab used to raise and lower the external guide 
 
 
Figure 4: EAZ101 sternal tunneling tool 
 
 
The 
Oscor SafeSheath® II (Model SSCL9) introducer (section 6.1.5)  is to be used with the sternal 
tunneling tool.   
 
 

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  Transverse Tunneling tool (Model EAZ201) 
The Medtronic Model EAZ201 transverse tunneling tool, shown in Figure 5, is an investigational tool 
designed to deliver the proximal portion of an extravascular lead to the device pocket during implant 
of an extravascular implantable device system. This is referred to as Zone 2 in Table 4: Outline of the 
proposed implant procedure steps. 
 
Figure 5: EAZ201 transverse tunneling tool 
 
 
 
 
   
If additional tunneling tools are used to tunnel the lead subcutaneously, this shall be discussed with 
Medtronic clinical study personnel prior to use and the tools used will be documented. Use of 
additional tools will be considered a study deviation.  
  Oscor SafeSheath® II Model SSCL9 
The Oscor (Palm Harbor, FL) SafeSheath® II Model SSCL9 introducer is a hemostatic tear-away 
introducer. 
  A 10cc 
plastic syringe will be packaged with the introducer sheath. The introducer sheath and hemostatic 
valve are indicated for the introduction of various types of pacing leads and catheters. The infusion 
side port is used to inject or aspirate through the sheath. 

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In this study, the SSCL9 introducer is used over the tunneling rod of the EAZ101 sternal tunneling 
tool to create a tunnel and facilitate insertion of the EV2401 extravascular lead into the mediastinum 
with a saline-filled syringe connected to the infusion sideport.  
 
Figure 6: The Oscor SafeSheath® II Model SSCL9 
The Oscor SafeSheath® II Model SSCL9 introducer is considered investigational in all geographies but 
may become commercially available during the course of the study. 
 EV ICD Programmer Software (Model SW041), Medtronic CareLink 
2090 Programmer with Analyzer and Medtronic CareLink Encore 
29901 Programmer  
The investigational Medtronic Model SW041 programmer software, Version 8.3.1 (or greater) runs 
on the commercially available Medtronic CareLink 2090 Programmer or the commercially available 
Medtronic CareLink Encore 29901 Programmer, both with Conexus telemetry, and communicates 
with an implanted EV ICD Model DVEX3E4. Following software download, the Medtronic 
Programmer 2090 or 29901 will be labeled per local requirements to indicate that it contains 
investigational software.  
Within its intended use, the programmer and programmer software will be used to provide a user 
interface with which the user can interrogate the device, control induction, shocking, sensing and 
pacing features and their parameters, and display diagnostic information. At implant, the 2090 
analyzer (which is part of the 2090 programmer) will be used to test the lead electrical signals before 
the device is implanted.  
 MyCareLink Patient Monitor (Model 24952) 
The commercially available Model 24952 MyCareLink Patient Monitor may be made available to 
subjects during this study when CareLink is made available for use with EV ICD. The MyCareLink 

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Patient Monitor communicates with an implanted EV ICD Model DVEX3E4 device to transmit data 
about device episodes to the subject’s clinic using the CareLink network. In this study, the CareLink 
monitor will be used within its intended use, but will be considered investigational when used with 
EV ICD until the firmware is approved for use with the EV ICD system.  
6.2. Manufacturer 
All of the EV ICD System and accessory components are manufactured by Medtronic, with the 
exception of the SSCL9 introducer sheath, manufactured by Oscor, Inc.  
Manufacturer Name 
Manufacturer Address 
Medtronic 
710 Medtronic Parkway 
Minneapolis, MN 55432 
USA 
www.medtronic.com 
+1 763 514 4000 
6.3. Packaging 
For investigational products, the device labeling and clinical manuals will be translated into the local 
language. The Clinical Manuals or Instructions for Use (IFU) will accompany each investigational 
component. Investigational products will be clearly labeled, e.g., “Exclusively for clinical 
investigations” and with the study identifier “MDT-1119” per local requirements. In some 
geographies, the IFUs may be delivered via an alternate format (e.g., CD-ROM format, USB, or 
electronic format) if allowed within local requirements. 
The investigational Medtronic Model SW041 programmer software application may be installed 
onto the Medtronic CareLink 2090 or Medtronic CareLink Encore 29901 programmers using USB 
drives with SW041 or Software Distribution Network (SDN) (if available); media packaging 
requirements are not applicable for distribution via the SDN. USB drives containing SW041, will be 
clearly labeled with identifier, version, and marked as “Exclusively for clinical investigations”. 
When investigational Medtronic Model SW041 software is installed on the 2090 or 29901 Medtronic 
Programmers, the Medtronic Programmers will be labeled to indicate they contain investigational 
software per local requirements. 
Packaging and labeling for all other market approved system components can be found with each 
package insert. Manuals for market approved Medtronic devices can be found on 
http://manuals.medtronic.com. For CE marked devices and market devices in Japan, the labeling is 
in the appropriate local language.  
The labeling for all components may include but is not limited to the following: 
• 
For study use only 

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• 
Study Device Identifier 
• 
Model number 
• 
Lot number 
• 
Storage condition 
• 
Expiration date 
• 
Name and address of sponsor 
The Medtronic EV ICD System is indicated for the automated treatment of patients who have 
experienced, or are at significant risk of developing, life-threatening ventricular tachyarrhythmias. 
The intended population to receive the EV ICD System includes patients who are indicated for 
implantation of a single chamber ICD according to current ACC/AHA/HRS or ESC guidelines, and who 
do not have a bradycardia pacing or cardiac resynchronization therapy indication.  
6.4. Intended Population 
The Medtronic EV ICD System is indicated for the automated treatment of patients who have 
experienced, or are at significant risk of developing, life-threatening ventricular tachyarrhythmias. 
The intended population to receive the EV ICD System includes patients who are indicated for 
implantationof a single chamber ICD according to current ACC/AHA/HRS or ESC guidelines, and who 
do not have a 
bradycardia pacing or cardiac resynchronization therapy indication. 
6.5.  Equipment 
Sites are responsible for maintaining and calibrating site equipment used in the course of this study 
(e.g., radiograph machine and fluoroscope) as applicable in accordance with established site practice 
and local regulation. Records shall be kept and available to be provided during monitoring visits and 
upon request by the Sponsor or regulatory agency.  
6.6. Product Use 
Instructions for installation and use for the components of the EV ICD System and accessories are 
located in the accompanying IFU for each component. Additionally, trained and experienced 
Medtronic personnel will provide support at implant.  
6.7.  Product Training Requirements 
The EV ICD implant procedure is to be performed by an investigator who has received training on all 
aspects of the implant procedure, including but not limited to:  
• 
Access into the anterior mediastinum, 
• 
Substernal tunneling (Zone 1),  
• 
Lead anchoring technique 
• 
Transverse tunneling to the device pocket (Zone 2),  
• 
Device pocket creation, and  

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• 
Implant device testing 
All implant training will be documented in the Investigator Site File (ISF). 
During the implant procedure, the investigator will be placing the lead utilizing a tunneling 
procedure. It is imperative that methods are utilized to ensure safe access to the anterior 
mediastinum via a sub-xiphoid approach. As cardiothoracic surgeons routinely perform midline 
sternotomy procedures, Medtronic intends to use a team approach during the EV ICD implant to 
ensure the knowledge and skills are transferred to a non-surgical physician specialty 
(EP/Cardiologist). A Cardiac Surgeon/Cardiothoracic Surgeon trained on relevant components of the 
study procedure will attend, at minimum, the first five implant procedures attempted by each 
implanting physician to partner on safe blunt dissection technique for tunneling into the anterior 
mediastinum and support the implant procedure. The Cardiac Surgeon/Cardiothoracic Surgeon can 
also add context to specific subject anatomy. It is required that the Cardiac Surgeon/Cardiothoracic 
Surgeon will also provide emergency support during all clinical study implant procedures.  
6.8. Product Receipt, Tracking, and Accountability 
The EV ICD System components (EV ICD, lead) and accessory components (sternal tunneling tool, 
transverse tunneling tool, SafeSheath introducer, software, and MyCareLink Patient Monitor), will be 
considered investigational in geographies in which the product is not available commercially and will 
be labeled for exclusive use in clinical investigations. Investigational system components will be 
distributed to a site only when Medtronic has received all required documentation (not limited to, 
Ethics Committee or Competent Authority approval, a signed Clinical Trial Agreement, and 
documentation of training) and has notified the site of site readiness.  
Distribution of the investigational product to study sites will be managed by Medtronic and 
investigational products may only be ordered by Medtronic personnel. Sites with these clinically 
labeled EV ICD System components will track disposition upon receipt or return of the components, 
as well as upon implant or explant of the components. 
Product accountability will be documented on the Device Accountability electronic Case Report 
Form (eCRF), which will be maintained in the Electronic Data Capture (EDC) system.  
This eCRF will track, at a minimum, the following information:  
• 
Date of receipt 
• 
Identification of the investigational components, if applicable (Lot or serial number or 
unique code) 
• 
Expiration date, if applicable 
• 
Date used or installed 
• 
Subject identification (ID) Number, if applicable 
• 
Date and reason for return or disposal, if applicable 
• 
Name of person responsible for receipt, return or destruction/disposal, if applicable 

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• 
Uninstallation or explant date of the investigational components and software, if 
applicable 
Medtronic will perform internal final study product reconciliation per the applicable study-specific 
document or per local requirements, to ensure all study product has been accounted for either by 
physical return to Medtronic or documented disposal at the site or vendor (including method of 
disposal). Periodic reconciliation of investigational product will be performed to ensure traceability.  
6.9.  Product Storage 
All investigational products must be stored in accordance with their labelling in a secure location at 
the site with access limited only to authorized personnel. It is the responsibility of the investigator to 
correctly handle, store, and track the investigational products. If allowed per local regulations, the 
programmer installed with the investigational software may be used for commercial use as the 
software can only communicate with investigational EV ICD devices. 
6.10.  Product Return 
All explanted, open but unused and potentially defective products (device, leads, tools, etc.) should 
be returned to Medtronic for analysis whenever possible and when permissible by local laws and 
regulations. If the products are explanted but not returned, a justification is required to be reported 
on the appropriate eCRF(s) (note that this is not considered a study deviation). The Device 
Accountability eCRF must be updated in the event of an explant. Local Medtronic field personnel or 
representative can be contacted to receive a Return Mailer Kit. All unused investigational products 
must be returned to Medtronic upon study closure at the site.  
The SW041 software may remain installed on specific 2090 programmers for the purposes of 
providing support for subject’s EV ICD System after the study is closed. If SW041 software is no 
longer required (e.g., replaced by updated market-released software), the SW041 software will be 
removed from the 2090 or 29901 programmers manually. 
7. Selection of Subjects 
7.1. Study Population 
The study population will consist of subjects who have class I or IIa indication for implantation of a 
single chamber Implantable Cardioverter Defibrillator (ICD) according to current ACC/AHA/HRS or 
ESC guidelines, and who do not have a bradycardia pacing or cardiac resynchronization therapy 
indication.  

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7.2. Subject Enrollment 
Patients will be screened to ensure they meet all the inclusion and none of the exclusion criteria.  
Subjects are considered enrolled in the study upon signing the Informed Consent Form. Informed 
Consent must be obtained prior to performing any study-related procedures. 
7.3. Inclusion Criteria 
 
Inclusion Criteria 
Rationale 
1. 
Patient has a Class I or IIa indication for implantation of 
an ICD according to the ACC/AHA/HRS Guidelinesviii, or 
ESC guidelinesix. 
Study will be evaluated in the standard patient 
population that is indicated for the device 
under evaluation. 
2. 
Patient is at least 18 years of age and meets age 
requirements per local law. 
Ensure age is appropriate to provide Informed 
Consent. 
3. 
Patient is geographically stable and willing and able to 
complete the study procedures and visits for the 
duration of the follow-up. 
Ensure ascertainment of data required for 
clinical evaluation. 
 
7.4. Exclusion Criteria 
 
Exclusion Criteria 
Rationale 
1. 
Patient is unwilling or unable to personally provide 
Informed Consent. 
Not allowing legally authorized 
representatives. 
2. 
Patient has indications for bradycardia pacing x or 
Cardiac Resynchronization Therapy (CRT) xi (Class I, IIa, 
or IIb indication).  
First generation of system does not include 
chronic bradycardia pacing support and does 
not include a left ventricular lead. 
3. 
Patients with an existing pacemaker, ICD, or CRT device 
or leads. 
Avoid possible confounding factors (e.g., 
complications due to changeout procedure). 
Subjects who have recently had a system 
removal may be considered if the physician 
 
viii Al-Khatib SM, Stevenson WG, Ackerman MJ, Bryant WJ, Callans DJ, Curtis AB, Deal BJ, Dickfeld T, Field ME, Fonarow GC, 
Gillis AM, Hlatky MA, Granger CB, Hammill SC, Joglar JA, Kay GN, Matlock DD, Myerburg RJ, Page RL. 2017 AHA/ACC/HRS 
guideline for management of patients with ventricular arrhythmias. 
ix Priori SG, Blomstrom-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, Elliot PM, Fitzsimons D, Hatala R, Hindricks 
G, Kirchhof P, Kjeldsen K, Kuck KH, Hernandez-Madrid A, Nikolaou N, Norekval TM, Spaulding C, Van Veldhuisen DJ. 2015 
ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. 
European Heart Journal 2015 36:41 (2793-2867). https://doi.org/10.1093/eurheartj/ehv316 
x 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator 
programming and testing). 
xi ACC/AHA/HRS guidelines for Cardiac Resynchronization Therapy 

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Exclusion Criteria 
Rationale 
feels procedure complications and/or 
infections are resolved.  
4. 
Patients with these medical interventions are excluded 
from participation in the study: 
• 
Prior sternotomy 
• 
Any prior medical condition or procedure that 
leads to adhesions in the anterior mediastinal 
space (i.e., prior mediastinal instrumentation, 
mediastinitis) 
• 
Prior abdominal surgery in the epigastric region 
• 
Planned sternotomy 
• 
Prior chest radiotherapy 
Or any other prior/planned medical intervention not 
listed that precludes their participation in the opinion 
of the Investigator. 
Avoid possible surgical risks during the 
tunneling procedure due to fibrosis or 
scarring in the mediastinal tissue. 
5. 
Patient has previous pericarditis that: 
• 
Was chronic and recurrent, or  
• 
Resulted in pericardial effusion xii, or 
• 
Resulted in pericardial thickening or 
calcification. xiii 
Avoid possible surgical risks related to the 
tunneling procedure arising from clinically 
significant pericarditis. 
6. 
Patients with these medical conditions or anatomies 
are excluded from participation in the study: 
• 
Hiatal hernia that distorts mediastinal anatomy 
• 
Marked sternal abnormality (e.g., pectus 
excavatum) 
• 
Decompensated heart failure 
• 
COPD with oxygen dependence 
• 
Gross hepatosplenomegaly 
Or any other known medical condition or anatomy type 
not listed that precludes their participation in the 
opinion of the Investigator. 
Excluded due to anatomical abnormalities 
that increase procedure risk, increased risk of 
infection, or risk of potential comorbidities 
that impact evaluation of the system during a 
clinical study. 
7. 
Patients with a medical condition that precludes them 
from undergoing defibrillation testing:  
• 
Severe aortic stenosis 
• 
Current Intracardiac LA or LV thrombus 
• 
Severe proximal three-vessel or left main coronary 
artery disease without revascularization 
Exclude patients who may be more 
vulnerable to potential increased risk during 
the evaluation of the clinical study 
defibrillation protocol.  
 
xii As documented on echo or MRI 
xiii As documented on CT scan or MRI 

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Exclusion Criteria 
Rationale 
• 
Hemodynamic instability 
• 
Unstable angina 
• 
Recent stroke or transient ischemic attack (within 
the last 6 months) 
• 
Known inadequate external defibrillation 
• 
LVEF < 20% 
• 
LVEDD >70 mm 
Or any other known medical condition not listed that 
precludes their participation in the opinion of the 
Investigator. 
8. 
Patient with any evidence of active infection or 
undergoing treatment for an infection. 
Standard exclusion criterion for device 
implant, emphasized due to importance. 
9. 
Patient is contraindicated from temporary suspension 
of oral/systemic anticoagulation   
To reduce risk of bleeding/hematoma 
intraprocedurally or in the event that an 
urgent sternotomy/thoracotomy is required 
10. 
Patient with current implantation of neurostimulator or 
any other chronically implanted device that delivers 
current in the body. 
For the purposes of clinical data collection 
and interpretation it is preferable to avoid 
any possible electrical interference with the 
EV ICD System. 
11. 
Patient meets ACC/AHA/HRS or ESC clinical guideline 
Class III criteria for an ICD (e.g., life expectancy of less 
than 12 months). 
 
Standard exclusion criterion to ensure study 
cohort is expected to survive to the time of 
endpoint evaluation and to ensure the study 
only includes patients with current clinical 
indications for an ICD. 
12. 
Patient is enrolled or planning to enroll in a concurrent 
clinical study that may confound the results of this 
study, without documented pre-approval from a 
Medtronic study manager. 
Standard exclusion criterion to avoid 
confounding procedural requirements due to 
multiple experimental studies. 
13. 
Patient with any exclusion criteria as required by local 
law (e.g., age or other).  
Standard exclusion criterion to comply with 
any additional local requirements which may 
apply.  
14. 
Pregnant women or breastfeeding women, or women 
of child bearing potential and who are not on a reliable 
form of birth regulation method or abstinence. xiv  
Pregnant women are excluded to avoid harm 
to the fetus caused by fluoroscopy 
requirements. 
 
xiv Women of child-bearing potential must undergo a pregnancy test within seven days prior to EV ICD Japan Study 
procedures 

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8. Study Procedures  
The following criteria were considered when selecting sites for the EV ICD Japan Study: 
• 
Investigator/site is qualified by training, education, and relevant experience appropriate to 
the use of the product and associated procedures 
• 
Investigator/site expects to have adequate time and resources to conduct the study 
throughout the duration of the study 
• 
Investigator/site has access to an adequate number of eligible subjects 
• 
Ability to comply with applicable Ethics Committee and regulatory requirements 
• 
Investigator is not debarred, disqualified, or working under sanctions in applicable regions 
• 
Site has demonstrated experience working (well) with Medtronic clinical research in the last 
3 years 
• 
Site can support timely data entry (e.g., coordinator) 
• 
Site has the ability to do full (90°) lateral fluoroscopy (biplane preferred), anesthesia, and 
the ability to treat AEs that require surgical intervention in the location where they plan to 
perform the procedure 
• 
Investigator(s) is willing and able to attend hands on implant training as outlined in section 
6.7 (1-2 implanting investigators per site) 
• 
Site has a robust emergency protocol - site can react to need for major cardiac surgery 
within 10 minutes 
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.  
During the activation process (prior to subject enrollment), Medtronic will train site personnel on, 
but not limited to, the current version of the CIP, relevant standards and regulations, Informed 
Consent process, data collection and reporting tools. In addition, site personnel must be delegated 
by the Principal Investigator to perform study-related activities. If new members join the site team, 
required documentation will be obtained and they will receive training on the applicable clinical 
investigation requirements relevant to their role before contributing to the clinical investigation. 
Medtronic will provide each study site with written documentation of study site/investigator 
readiness. In order to receive written documentation of study site/investigator readiness, the 
following documentation must be available: 
• 
Regulatory authority approval 
• 
Ethics Committee approval and voting list 
• 
Signed Clinical Trial Agreement 
• 
Current CVs for investigators, signed and dated 
• 
Confirmation of receipt of IB, if available 
 

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Prior to performing study-related procedures, all sites must have Ethics Committee and associated 
regulatory authority approval if applicable as well as documentation from Medtronic of site 
readiness.  
8.1. Schedule of Events 
Visit schedule and data collection requirements are summarized below in Table 2.  

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Table 2: EV ICD Japan Study schedule of events 
Study procedure 
Baseline 
Implant 
PHD 
2 Weeks  
3 Months 
6 Months 
Long-Term (12, 18, 
24…months)  
Unsched. 
Sys. Mod. 
Exit 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Assessment 
X 
 
 
 
 
 
 
 
 
 
Physical Exam, Demographics, Cardiovascular Medical 
History, Surgical History 
X 
 
 
 
 
 
 
 
 
 
SF-12 quality of life survey 
X 
 
 
 
 
X 
 
 
 
 
System and procedure information 
 
X 
 
 
 
 
 
 
X 
 
Pre-procedure Transesophageal Echocardiogram (TEE)1 
 
X1 
 
 
 
 
 
 
 
 
CT or MRI scan  
X2 
 
 
 
 
 
 
 
 
 
Fluoroscopy recordings during tunneling procedure 
 
X 
 
 
 
 
 
 
X4 
 
Fluoroscopy (AP and Lateral cine) of final ICD generator and 
lead position 
 
X 
 
 
 
 
 
 
X4 
 
Sensing, Impedance & Pacing Tests 
 
X 
X 
X 
X 
X 
X 
X3 
X4 
 
Defibrillation Testing 
 
X 
 
 
 
 
 
 
X4 
 
Chest Radiographs – (PA/Lateral) 
X 
 
X 
 
 
 
 
 
 
 
Echocardiographic data within the last 6 months 
X 
 
 
 
 
 
 
 
 
 
Save-to-media files  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medications (for subjects implanted with any device) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events5 (including AEs with fatal outcome), Device 
Deficiencies, HCUs, Study Deviations, and Other Cardiac 
Imaging 
As they occur 
1 Required for subjects presenting in atrial fibrillation to confirm the absence of LA or LV thrombus. 
2 Taken within the last year. Recommended for first 3 subjects at minimum, for each implanter. If collected/reviewed, send CT-scan and/or MRI to Medtronic. 
3 Optional. If electrical testing conducted, print the Testing Reports to PDF or paper and send a copy of the reports to Medtronic 
4 System modification where a subject leaves the procedure with an EV ICD System. 
5 Recommended to collect incision photographs if an infection related to the EV ICD System is suspected.   

 
 
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8.2. Medications 
Medication details will be collected via electronic case report forms (eCRFs) on a rolling basis 
throughout the study. Document all oral and intravenous medications prescribed to the subject at the time 
of the Baseline visit on the eCRFs and continue to document medication changes (when medications are 
stopped or started) throughout the subject’s participation in the study. In addition, medications administered or 
adjusted to treat a reported adverse event shall be reported. If the subject is not implanted or attempted to be 
implanted, medication collection is not required. 
 Prior and Concomitant Medications 
There are no restrictions regarding prior or concomitant medications, with the exception of 
oral/systemic anticoagulants per study exclusion criteria (section 7.4).  
8.3. Subject Consent 
Informed Consent (IC) is defined as a legally effective documented confirmation of a subject’s voluntary 
agreement to participate in a particular clinical study. This confirmation occurs 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 (ISO 14155:2020). This process includes obtaining an Informed Consent Form (ICF) and an 
Authorization to Use and Disclose Personal Health Information/Research Authorization/other privacy 
language as required by law. The ICF and Authorization to Use and Disclose Personal Health 
Information/Research Authorization/other privacy language as required by law shall be approved by 
Medtronic and each study site’s Ethics Committee (EC) prior to enrolling subjects. These shall be signed 
and personally dated by the subject and the Principal Investigator or authorized designee as required.  
The document(s) must be controlled (i.e., versioned and dated) to ensure it is clear which version(s) 
was/were approved by Medtronic and the EC. Any adaptation of the previously approved ICF must be 
reviewed and approved by Medtronic and the EC prior to being used to consent or re-consent a study 
subject. 
The investigator must notify the subject of any significant new findings about the study that become 
available during the course of the study which are pertinent to the safety and well-being of the subject, 
as this could impact a subject’s willingness to participate in the study. If relevant, subjects must be 
requested to confirm their continued participation in writing.  
Prior to initiation of any study-specific procedures, IC must be obtained from the subject.  

 
 
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The process of obtaining Informed Consent shall: 
• 
Ensure that the Principal Investigator or an authorized designee conducts the IC process. 
• 
Include all aspects of the EV ICD Japan Study that are relevant to the subject's decision to 
participate throughout the clinical study. 
• 
Avoid any coercion or undue improper influence on, or inducement of the subject to 
participate. 
• 
Not waive or appear to waive the subject’s legal rights. 
• 
Ensure the ICF and Authorization to Use and Disclose Personal Health Information/Research 
Authorization/ other privacy language, as required by law, are given to the subject in a non-
technical language the subject is able to read and understand. 
• 
Provide ample time and opportunity for the subject to read and understand the ICF to inquire 
about details of the study, and to consider participation. All questions about the study should 
be answered to the satisfaction of the subject. 
• 
Include a personally dated signature of the subject acknowledging that their participation in 
the study is voluntary. 
• 
Include a personally dated signature of the Principal Investigator or authorized designee 
responsible for conducting the IC process, as required by local law. 
• 
Include any other locally required signatories, such as witnesses, as indicated by country-
specific legislations. 
• 
Provide the subject with a copy of the ICF and Authorization to Use and Disclose Personal 
Health Information/Research Authorization/ other privacy language as required by law, and 
any other written information, signed and dated if required by local law.   
• 
Ensure subject is notified of any significant new findings about the study that become available 
during the course of the study which are pertinent to the safety and well-being of the subject, 
as this could impact a subject’s willingness to participate in the study. 
If the IC 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. The IC process shall be documented in the subject’s case history, regardless 
of circumstance. 
In the event the subject cannot read and/or write, and if allowed by local law, the IC shall be obtained 
through a supervised oral process. An independent witness (if applicable as per local regulation) must 
be present during this process. The ICF and any other information must be read aloud and explained to 
the prospective subject, and whenever possible, either the witness or prospective subject shall sign and 
personally date the ICF attesting that the information was accurately explained, and that IC was freely 
given. The source documentation shall provide the method 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 original signed ICF must be filed in the hospital/clinical chart and/or with the subject’s study 
documents. 
A copy of ICF signed by the investigator and the prospective subject shall be provided to the subject. 
The ICF and Authorization to Use and Disclose Personal Health Information/Research Authorization/ 
other privacy language shall be available for monitoring and auditing if required by law. Any Medtronic 
personnel who support the study procedure must be able to review the subject’s signed and dated ICF 
and verify its completeness prior to proceeding with the study procedure. In the event the Medtronic 
personnel identify the ICF as being incomplete, the study procedure will not be allowed to occur until 
the consent of the subject can be adequately and appropriately obtained. 
Only the monitor assigned to this study may be able to review the signed IC as direct access or source 
data verification. 
8.4. Enrollment / Baseline 
When a patient and the Principal Investigator or authorized designee (if applicable) signs and dates the 
ICF, the patient is considered a subject enrolled in the study. The date the subject signed the ICF must 
be documented in the subject’s medical records. Enrollment can be a stand-alone visit or can occur on 
the same day as the baseline visit. Medtronic shall be notified (via Enrollment eCRF) as soon as possible 
to aid in enrollment tracking. Once consent is obtained, report adverse events, device deficiencies, 
study deviations, system modifications, and subject exits or deaths as they occur. 
The following information is required to be collected at the baseline visit: 
• 
Confirmation of Inclusion/Exclusion Criteria 
o It is recommended to perform a pre-implant anatomy evaluation (see section 8.4.1) 
• 
Demographics 
• 
Physical exam: A basic physical exam will be performed, including height and weight  
• 
Relevant medication and relevant cardiovascular medical history 
• 
Relevant surgical history 
• 
Primary indication for ICD implant 
• 
Echocardiographic data within the last 6 months 
• 
SF-12 quality of life survey 
• 
Chest radiograph, standing tidal inhalation breath hold (see Table 3) 
o Radiographs shall be sent to Medtronic (see section 8.9) 

 
 
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Table 3: Chest Radiograph collection during Baseline Visit 
Visit 
Image Collection 
Baseline 
• 
Standing PA → Tidal inhalation breath hold 
• 
Standing LAT → Tidal inhalation breath hold 
 
 Subject Pre-implant Anatomy Evaluation  
Assess the subject in a supine position to evaluate potential abdominal interference to safely access 
substernal space and operator’s ability to palpate xiphoid process, costal-rib margins and left sternal 
border to confirm the subject does not meet exclusion criterion 6.  
Review the baseline chest radiographs. It is also recommended to review a CT-scan (cardiac gated 
preferred) or MRI (taken within the last year) for the first 3 subjects at minimum, for each implanter. 
Imaging may help with pre-procedure planning and assessment of the subject’s anatomy. If the 
implanter feels the subject has unfavorable mediastinal anatomy, the procedure shall not be 
attempted, and the subject shall be exited from the study (see section 8.19 Subject Withdrawal or 
Discontinuation).  
If collected/reviewed, send CT-scan and/or MRI to Medtronic (see section 8.9). This information will be 
used to further characterize clinical results and anatomical considerations. 
8.5. Implant Visit 
It is recommended that the implant visit occurs within 30 days of study enrollment.   
 Antibiotic and Infection Control Strategies  
Prophylactic antibiotic administration per standard of care (e.g., as specified by the site policies) is 
required. Standard hospital procedures shall be followed regarding antibiotic therapy for ICD 
implantation.  
 
 Anticoagulation 
It is required that subjects on anticoagulants have oral and/or systemic anticoagulants withheld peri-
procedurally in order to reduce risk of bleeding/hematoma, as follows: 

 
 
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Pre-procedure: 
• 
Withhold anticoagulants per local protocol.  
• 
Follow the treatment procedures suggested by the drug manufacturer for timing of temporary 
discontinuation. 
• 
Recommendations by anticoagulant type include: 
• 
Suspension of novel oral anticoagulants (NOACs) ≥24 hours pre-procedure 
• 
Suspension of heparin ≥6 hours pre-procedure 
• 
Suspension of low molecular weight heparin ≥72 hours pre-procedure 
• 
Suspension of warfarin ≥48 hours pre-procedure 
 
Post-procedure: 
• 
It is recommended to resume oral anticoagulation as soon as possible post-procedurally unless 
clinically contraindicated (e.g. effusion observed).  
 
• 
Post-procedure anticoagulation should be resumed as soon as possible unless clinically 
contraindicated in patients who have had AF for ≥ 48 hours in duration prior to the implant 
procedure and who convert to sinus rhythm during defibrillation testing to diminish the risk of 
peri-procedural stroke. 
 
Document all medication changes on the Medications eCRF. 
 Dual antiplatelet therapy 
Patients on dual antiplatelet therapy will be treated per standard of care, at physician discretion. 
 Fluoroscopy and Photography 
Prior to inserting the sternal tunneling tool into the mediastinal space, the investigator is required to 
review AP and Lateral fluoroscopy to determine the best incision location and angle of entry. The 
investigator should consider the subject’s BMI and abdomen when in the supine position, as it may 
challenge safe tool utilization. If the investigator does not believe he/she can maintain close proximity 
to, or contact with, the posterior of the sternum with the tip of tunneling tool, the investigator should 
not proceed with the EV ICD implant procedure.  
In the event that the investigator does not proceed with the implant procedure: 
• 
AP and lateral fluoroscopic images or videos must be sent to Medtronic. These data will help 
further the understanding of anatomic variances for future procedure development 
considerations.  

 
 
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In cases where the investigator does proceed with the implant procedure: 
• 
Collect fluoroscopy cine recordings during the substernal tunneling with the sternal tunneling tool 
and introducer as well as during EV ICD lead placement.  
• 
Two fluoroscopy cine images (AP and Lateral) are required of the final EV ICD lead placement and 
device placement for one full respiration cycle.   
• 
Fluoroscopy cine recordings and cine images will be will be sent to Medtronic (see section 8.9).  
 Implant Procedure Steps 
Prior to performing the implant procedure, it is important that implanting investigators read and 
understand the Instructions for Use (IFU) that accompanies each device and undergo documented 
training by Medtronic.  
It is strongly recommended to use general anesthesia with cardiac monitoring during the implant 
procedure to prevent subject movement and minimize the likelihood of adverse events during 
procedure. Additionally, general anesthesia will afford a greater level of cardiac monitoring compared 
to what is practiced when patients are under conscious sedation. 
If the procedure is aborted at any point, refer to section 8.19 for additional instructions. 
The proposed procedure steps are listed in Table 4. The steps are strongly recommended unless 
otherwise noted as required steps.  
Table 4: Outline of the proposed implant procedure steps 
Implant Step 
Procedure + Imaging 
1. Subject Assessment  
• 
Review pre-procedure chest imaging.  
• 
Required: Pre-procedural fluoroscopy in both Lateral and AP views is 
required prior to starting the implant procedure to assist in 
determining sub-xiphoid incision location for the patient anatomy, to 
determine whether the sternal tunneling tool tunnel rod curvature 
needs adjustment based on subject anatomy, to assist in sternal 
tunneling tool entry into the substernal space to inform the angle of 
insertion, and identification of appropriate device pocket location. 
• 
If the implanter cannot find a way to achieve or maintain consistent 
contact or close proximity between the distal tip of the tunneling rod 
and the sternum during insertion or advancement, the procedure 
should be stopped. 

 
 
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Implant Step 
Procedure + Imaging 
• 
Required: If subject presents in atrial fibrillation, perform a pre-
procedure TEE to ensure the absence of LA or LV thrombus. 
2. Subject Preparation 
and Drape 
• 
Place 1 set of External Defibrillation Patches in locations that will not 
compromise the implanted system defibrillation vector or sterile 
operating field. 
• 
Position left arm to allow full lateral fluoroscopy and pocket incision 
access on left mid-axillary chest. 
• 
Determine ICD pocket location using fluoroscopy (AP & Lateral 
views) and the cardiac silhouette as guidance with demonstration 
lead and ICD.   
• 
Draw surface landmarks on chest, including sternal midline, left 
sternal border, xiphoid process, costal margins, top of cardiac 
silhouette and incision location and device pocket location. 
• 
Perform sterile preparation of the chest for implant per Standard of 
Care. 
• 
Drape patient chest to provide sterile operating field to access the 
sub-xiphoid and device pocket incisions. 
3. Sternal Tool and 
Introducer Preparation 
• 
If needed, manually bend the tunneling rod of the sternal tunneling 
tool to a curvature suitable for the patient’s anatomy. The angle 
should allow for the tunneling rod tip to remain in contact with (or 
as close as possible to) the posterior of the sternum during 
tunneling.  
• 
Prepare introducer sheath according to manufacturer’s instructions 
for use and load onto the tunneling rod of sternal tool. 
• 
Attach a pre-filled saline syringe (10 cc) to hemostasis valve side-port 
on introducer with valve open for the implant procedure. 
4. Sub-Xiphoid Access 
• 
Make an incision below the xiphoid process and left of sternal 
midline.  Anatomical variation adjustments may be necessary: 
o Consider the margins of the left costal rib and xiphoid 
process.  A lower incision may be required in larger patients 
to allow for shallow blunt dissection and <30-degree angle of 
 

 
 
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Implant Step 
Procedure + Imaging 
a medical instrument or tunneling rod insertion. 
5. Blunt Dissection of 
Diaphragmatic 
Attachments 
• 
Use a fingertip and/or curved Kelly hemostat to dissect through 
diaphragmatic attachments and confirm the tissue plane using 
lateral fluoroscopy for visualization.  
• 
Once the implanter has completed blunt dissection and has entered 
the mediastinal tissue plane, if resistance is felt (e.g., fibrotic 
attachments between heart and sternum), abort procedure. 
• 
Pre-lay 2 sutures into the rectus fascia (to later secure lead 
anchoring sleeve). 
6. Substernal Tunneling 
Procedure (Zone 1) 
• 
Insert prepared sternal tunneling rod using full Lateral fluoroscopy 
into anterior mediastinum. Keep tip of tunneling rod in contact or 
close to xiphisternal junction and sternum during insertion. 
• 
Tunnel approximately midline or just left of sternal midline and no 
further than the top of cardiac silhouette, as determined by AP 
Fluoroscopy and surface landmarks.  Keep tunneling rod in contact 
with or close to the posterior of sternum. If any resistance is felt, 
stop and confirm tunneling tool location in alternate fluoroscopic 
view. Redirect tunneling rod under the sternum. If patient has COPD 
or lungs crossing midline are suspected, consider tunneling during 
end-expiration apnea. 
• 
Confirm the pre-filled saline syringe (10 cc) is connected to 
hemostasis valve side-port on introducer sheath with valve open. 
• 
Retain the sheath in position, then slowly remove the sternal 
tunneling tool from the sheath and incision. 
7. EV ICD Lead 
Insertion and 
Deployment 
• 
Use AP fluoroscopy to insert the lead to the distal tip of the 
introducer sheath. 
• 
Required Lead Orientation: Defibrillation Coils toward subject’s right 
chest; Pace/Sense Rings toward patient’s left chest.  
• 
Position the lead with respect to the cardiac silhouette and intended 
 

 
 
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Implant Step 
Procedure + Imaging 
ICD location. 
• 
Deploy the lead by withdrawing the sheath out of the incision to 
expose the electrodes over cardiac silhouette for achieving adequate 
sensing, pacing and defibrillation. Retain the sheath until completion 
of Step 8.  
• 
In the event of the lead deployment in the opposite orientation (Coil 
1 and Coil 2 electrodes toward patient’s left lateral border), it is 
recommended to re-advance the introducer over the lead body to 
the distal tip. 
• 
Next, withdraw the lead and reinsert in the required orientation 
prior to acute testing.  
 
• 
Do not reinsert the lead through the introducer valve more than five 
times during the procedure. If this occurs, use a new lead. 
 
8. Assessment of EV 
ICD Lead 
• 
Evaluate R-wave signal amplitude for Ring1-Ring2 configuration, 
through one full respiration cycle, using Medtronic CareLink 
Programmer Model 2090 Analyzer. 
o Set up the 2090 Analyzer to new R-wave filter, ODO mode.  
Set sensitivity to appropriate setting. 
o Record the measured sensing values. 
• 
If R-wave amplitude is < 1mV for the Ring1-Ring2 configuration, or P-
wave or T-wave oversensing is suspected, attempt repositioning or 
re-tunneling the lead. If R-wave amplitude remains < 1mV, the 
implant shall be abandoned, and the implant of an alternative ICD 
system should be considered.  

 
 
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Implant Step 
Procedure + Imaging 
• 
Remove introducer sheath prior to sub-xiphoid suture sleeve 
fixation. 
9. Confirm Final Lead 
Placement 
• 
Ensure the Ring 2 electrode on the lead is not located caudal to the 
xiphoid tip to avoid possible lead damage. 
o Note: If the xiphoid tip is unidentifiable, do not implant the 
Ring 1 electrode caudal to the xiphisternal junction 
Example of final lead placement:
 
• 
If the distal portion of the lead is moving significantly, attempt 
repositioning or re-tunneling the lead to avoid possible damage. 
Example of significant distal lead motion: 
• 
 
 

 
 
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Implant Step 
Procedure + Imaging 
10. Sub-Xiphoid Suture 
Sleeve and Lead 
Fixation 
• 
Required: Use a minimum of three non-absorbable sutures with high 
tension force to fixate anchoring sleeve to lead body in sub-xiphoid 
incision using each of the three grooves.  
• 
Required: Tie two non-necrosing sutures to the fascia, then tie to 
lead anchoring sleeve grooves. Next, tie one suture onto the lead 
anchoring sleeve to secure to the lead body. 
11. Create EV ICD 
device pocket 
• 
Use fluoroscopy to confirm defibrillation vector based on final lead 
placement and cardiac silhouette for EV ICD device location. 
• 
Create device pocket incision near the left mid-axillary chest to form 
an optimized vector with the implanted lead. 
12. Transverse 
Subcutaneous 
Tunneling Procedure 
(Zone 2) 
• 
Insert distal tip of transverse subcutaneous tunneling rod in sub-
xiphoid incision, above/anterior to the costal rib margin and advance 
into the device pocket incision. 
• 
Remove handle to expose lead channel and insert lead connector pin 
into channel. 
• 
Pull tunneling rod with lead inserted in the channel into the device 
pocket incision.  Remove the transverse subcutaneous tunneling rod 
through the pocket incision. 
13. Device Pocket and 
Sub-Xiphoid Incision 
Closure 
• 
Fixate device header against fascial plane using non-absorbable 
suture in the holes provided. 
• 
If the TYRXTM Envelope is used, this shall be documented. 
• 
Remove air from incision and close the pocket and sub-xiphoid 
incisions, at least one layer, prior to device testing.  
• 
Final closure of incisions shall be in at least three layers, and wound 
dressings shall be applied per standard of care. 
14. Required Cine of 
final lead and device 
placement 
• 
Required: Cine, both AP & Lateral views during a full respiration 
cycle, to document final lead and EV ICD position. 
 

 
 
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Implant Step 
Procedure + Imaging 
15. EV ICD Device 
Testing 
• 
Interrogate the EV ICD device and perform electrical testing (sensing, 
pacing, impedance), as described in section 8.5.6. 
• 
Perform defibrillation testing protocol, as described in section 8.5.7. 
 
 Implant Testing – EV ICD System 
Perform the following tests of the EV ICD System after the EV2401 lead is connected to the EV ICD 
device and the device is placed into the pocket.  
8.5.6.1. Sensing Testing 
Perform an RV sensing test. Set ICD RV sensing vector to Ring1-Ring2. Adjust sensing parameters to 
avoid T-wave oversensing, P-wave oversensing, or other oversensing. Once configured, perform the 
Sensing Test. Print the Sensing Test Report on the programmer to PDF or paper and store at site. 
Evaluate alternate sensing vectors as necessary. Program determined sensing settings. 
The R-wave amplitude for sensing shall be greater than or equal to 1mV for the Ring1-Ring2 
configuration. 
If the R-wave amplitude is less than 1mV for the Ring1-Ring2 configuration after all troubleshooting 
attempts have been exhausted (refer to step 8 in Table 4), the EV ICD implant shall be abandoned and 
the implant of an alternative ICD system should be considered. 
8.5.6.2. Impedance Testing 
Subthreshold impedance will be measured for the following electrode pairs:  
• 
Ring1 to Ring2 
• 
Ring1 to Coil2 
• 
High Voltage 
Print the Lead Impedance Test Report to PDF or paper and send to Medtronic. 
8.5.6.3. Pacing Testing  
Pacing capture threshold testing will be performed, potentially in multiple vectors: Ring1-Coil2, Ring1-
Ring2, Coil2-Coil1.  Pacing capture is defined as at least three consecutive captured beats. 

 
 
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At the conclusion of pacing capture threshold testing, it is recommended to leave pacing settings at the 
shipped nominal values until pre-hospital discharge.  
Print final capture threshold report to PDF or paper and send to Medtronic. 
  Induction and Defibrillation Testing 
To ensure subject safety in an ambulatory setting, sustained shockable ventricular arrhythmia (SSVA) 
induction and defibrillation testing is required at implant. Adjust device programming to ensure 
adequate safety margins for sensing and defibrillation during SSVA induction testing.  
The testing protocol may require up to six successful SSVA episodes induced and up to 10 EV ICD 
shocks delivered (Figure 7).  
8.5.7.1. General Requirements 
Induction of SSVA will be achieved using one of the following methods: 
• 
Burst Induction (Coil2-Coil1, 40V) 
• 
T-shock (up to 20J) 
If a subject cannot be induced using these methods, other methods may be employed at the discretion 
of the investigator (e.g., EP catheter). The investigator may choose to attempt induction on another 
day prior to discharge. If the investigator determines the subject cannot be induced, the EV ICD System 
must be removed (refer to section 8.5.8).  
Ensure a Wavelet template is collected and EV ICD detection is enabled prior to induction. If the 
subject's health is at risk, defibrillation testing should be suspended or terminated. 
Ensure an external transthoracic defibrillation system is present and ready to deliver rescue shocks 
during defibrillation testing, and at least one set of rescue patches are in place in locations that will not 
compromise the implanted system defibrillation vector or sterile operating field. 
It is recommended to wait five minutes between the end of an SSVA episode and subsequent induction 
to ensure that the patient is hemodynamically stable. Waiting period after failed induction attempts is 
at the investigator's discretion. 
Defibrillation testing may continue on a future day if episodes remain within the testing protocol, but 
lead revision is not permitted on a future day if the subject has resumed anticoagulation.   
Anticoagulation should be resumed as soon as possible post-procedurally unless clinically 
contraindicated (e.g., effusion observed) in subjects who have presented in atrial fibrillation for ≥ 48 

 
 
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hours in duration prior to the implant procedure and who convert to sinus rhythm during defibrillation 
testing to diminish the risk of peri-procedural stroke. 
Reminder:  After each induced SSVA episode, save-to-media files shall be collected (see section 8.10). 
Print the live strip for the duration of each SSVA episode. Retain a copy of the live strip for each 
episode not recorded by the ICD. If requested, send a copy of the live strip to Medtronic (e.g., a scan). 
Print the VT/VF episode report to PDF or paper and store at the site.  
Record shock outcome and shock impedance (if available) for each EV ICD and rescue shock.  A shock 
will be considered successful if it results in termination of the induced SSVA episode, with termination 
defined as a return to normal intrinsic rhythm or to a supraventricular tachycardia before the next 
shock is given. Additional processing of the VF sensing data may be performed after implant data 
collection. 
8.5.7.2. Testing and Programming Defibrillation Therapy 
Defibrillation testing success is defined as meeting one of the following criteria: 
a. Single SSVA conversion at 20J, or  
b. Conversion of two consecutive episodes of SSVA at 30J in final system configuration. 
Follow the defibrillation testing as outlined in Figure 7, beginning at Episode 1 (20J). The following 
requirements shall be observed while conducting defibrillation testing: 
• 
Defibrillation at a given energy will be deemed successful if SSVA is terminated, regardless of 
whether the shock is delivered manually or automatically by device.  
• 
In one of the two consecutive SSVA episodes, up to two 30J shocks are permitted. 
• 
To achieve final system configuration, changing the position of the ICD generator and/or the 
lead, or changing shock polarity is permitted. 
• 
If the device or lead position are altered (e.g., position changed as part of troubleshooting), 
defibrillation success must be demonstrated with the new system configuration. 
• 
If defibrillation protocol episodes are not exhausted, remaining episodes may be used on a 
subsequent day (e.g., next day or during the admission) to complete the defibrillation testing 
protocol 
• 
For the first episode following the 20J therapy or the first 30J episode following a 
“Troubleshoot System” step in Figure 7, program Rx1 polarity to either STD or REV, and 
program Rx2 polarity the opposite of Rx1 polarity. 
• 
If the episode follows a defibrillation success at 30J, and the previous episode had a 
defibrillation success with Rx1, program Rx1 and Rx2 to the polarity of Rx1 in the previous 
episode. 

 
 
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• 
If the episode follows a defibrillation success at 30J, and the previous episode had a 
defibrillation success with Rx2, program Rx1 to the same polarity as Rx2 in the previous 
episode and program Rx2 off. 

 
 
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Figure 7: Diagram outlining the process of SSVA induction and defibrillation testing 

 
 
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8.5.7.3. Testing and Programming VF Detection 
VF detection success at implant is defined as successful VF detection in a single SSVA episode in the 
Ring1-Ring2 configuration at a value greater than or equal to 0.2 mV (e.g., 0.2, 0.45, or 0.6 mV). VF 
detection and defibrillation success do not need to be demonstrated on the same episode(s), but each 
must be demonstrated in the final system configuration. 
Follow the VF detection testing as outlined in Figure 8, beginning at Episode 1. This aligns with Episode 
1 for Defibrillation Testing outlined in Figure 7. The following requirements shall be observed while 
conducting VF detection testing: 
• 
The VF detection shall be demonstrated in the Ring1-Ring2 vector with a Number of Intervals to 
Detect (NID) setting of 30/40. 
• 
If VF detection is demonstrated in the Ring1-Ring2 vector, the remaining induction attempts may 
be programmed with a NID setting of 18/24. 
• 
Redetect NID shall be programmed to 9/12 when Rx2 is enabled. 
• 
Begin testing with VF Sensitivity programmed to Ring1-Ring2, 0.45 mV.  
• 
Use this setting when restarting testing to evaluate a new lead position. 
• 
If the first programmed setting is unsuccessful, program VF Sensitivity to Ring1-Ring2, 0.2 mV. 
• 
If the second programmed setting is unsuccessful, reposition the lead and test again with the first 
programmed VF Sensitivity setting of Ring1-Ring2, 0.45 mV. 
• 
If VF detection is demonstrated in the Ring1-Ring2 vector, program VF Sensitivity to Ring1-Can, 
0.45 mV. 
• 
Once VF detection is demonstrated in Ring1-Ring2 and attempted in Ring1-Can, VF detection shall 
be programmed to the Ring1-Ring2 vector for remaining induction attempts.  
• 
If desired, additional margin can be assessed by programming VF Sensitivity to 0.6 mV, otherwise 
it is recommended to complete the remaining induction attempts with Sensitivity programmed to 
0.15 mV.xv 
• 
Additional inductions beyond those specified in Figure 7 are allowed if needed per medical 
judgment (e.g., to program sensitivity or to obtain supplementary information on an alternate 
vector). 
• 
If the VF detection success is demonstrated in the Ring1-Ring2 vector, and the lead position is 
preserved, it is not necessary to re-demonstrate VF detection in the Ring1-Ring2 configuration, 
even if the device position is altered (e.g., as part of troubleshooting). 
 
xv In instances where detection has been demonstrated in the Ring1-Ring2 vector at 0.45 mV and the lead is not repositioned, 
subsequent episodes may be programmed Ring1-Ring2 at 0.15 mV, Ring1-Can at 0.45 mV, or Ring1-Ring2 at 0.6 mV to check 
for additional margin. Programming VF Sensitivity to 0.6 mV increases the likelihood that VF Detection will not occur, and 
delivery of a manual shock will be necessary.  

 
 
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• 
If the lead position is altered (e.g., as part of troubleshooting), previously demonstrated VF 
detection success is invalidated and success must be demonstrated with the new system 
configuration with an NID setting of 30/40. 

 
 
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Figure 8: Diagram outlining the process of VF sensing margin testing 
 
1 In instances where detection has been demonstrated in the Ring1-Ring2 vector at 0.45 mV and the lead is not repositioned, VF Sensitivity for subsequent episodes may be 
programmed to Ring1-Ring2 at 0.15 mV, Ring1-Can at 0.45 mV, or Ring1-Ring2 at 0.6 mV to check for additional margin. Programming VF Sensitivity to 0.6 mV increases the likelihood 
that VF detection will not occur, and delivery of a manual shock will be necessary. 
2 Ring1-Ring2 equal to or more sensitive than 0.20 mV programming option is only available if Ring1-Ring2 was tested successfully at 0.6 mV; Ring1-Ring2 equal to or more sensitive 
than 0.15 mV programming should be used if 0.6 mV was not successfully tested. 

 
 
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8.5.7.4. Implant Defibrillation Troubleshooting Recommendations 
Prior to inducing and throughout the defibrillation protocol, it is recommended to consider the 
following to improve defibrillation outcome or troubleshooting in the event of failure of first 
episode(s):  
• 
Check for/resolve pneumothorax 
• 
Check for/resolve high impedance values 
• 
Check for/resolve air in tunnel (e.g., fluoroscopy) 
• 
Check for/resolve air in pocket (e.g., flush with saline or antibiotic wash, massage air out of 
pocket) 
• 
Check for/resolve gastric bubbles (gas) 
• 
Press on device pocket during testing 
• 
Perform defibrillation during held end tidal expiration (end expiration apnea) 
• 
If all of the above measures are exhausted, evaluate the position of the EV ICD device and the EV 
ICD Lead. If required, consider repositioning of EV ICD generator or EV ICD lead.xvi 
• 
Allow time (e.g., next day or during the admission) to minimize transient factors affecting 
defibrillation success 
Note: Troubleshooting attempts after Episode 5 (Figure 7) may not leave enough remaining episodes to 
confirm both Defibrillation and VF detection success.  
8.5.7.5. Programming Requirements at End of Implant Procedure 
At the end of the procedure, VF Detection shall be ON and VF Therapies and Pacing therapies shall be 
programmed OFF until Pre-Hospital Discharge evaluation to prevent oversensing/undersensing prior to 
proper evaluation of threshold once the subject is ambulatory. While VF Therapies are OFF, the subject 
shall have cardiac monitoring.  
 Subject Exit for Incomplete Implant Visit 
The subject shall be exited if any of the following occur during the implant visit: 
• 
Incomplete Placement of Lead and/or Device – The EV ICD System is not fully implanted. 
 
xvi Lead revision is not permitted if the subject has resumed anticoagulation. Post-procedure anticoagulation should be 
resumed as soon as possible unless clinically contraindicated (e.g., effusion observed) in subjects who have had atrial 
fibrillation for ≥ 48 hours in duration prior to the implant procedure and who convert to sinus rhythm during defibrillation 
testing to diminish the risk of peri-procedural stroke. 

 
 
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• 
Incomplete Defibrillation Testing Protocol – The subject cannot complete the entire defibrillation 
testing protocol because they were not inducible or failed to induce a sufficient number of 
episodes. 
o 
Note: If the subject completes the initial implant procedure without completing the 
defibrillation testing protocol, the subject may be brought back prior to hospital 
discharge to complete the remainder of the defibrillation testing protocol, as outlined in 
Figure 7. 
• 
Failure of Defibrillation Testing Protocol – The subject completes the defibrillation testing protocol 
but does not meet the criteria for success for defibrillation testing. 
• 
Inadequate Sensing – The subject cannot achieve an R-wave ≥ 1 mV for the Ring1-Ring2 sensing 
vector after troubleshooting methods are exhausted. 
• 
Inadequate SSVA Detection – The subject cannot achieve successful VF detection in a single SSVA 
episode in the Ring1-Ring2 configuration at a value greater than or equal to 0.2 mV after 
troubleshooting methods are exhausted. 
If the subject does not complete the implant visit due to any of the reasons specified above, the EV ICD 
System shall be explanted, and the subject shall be followed and assessed for AEs through 30 days or 
until procedure or system related AEs have been resolved, at which point the subject can be exited (see 
section 8.19). If the subject receives an alternative system (e.g., S-ICD or TV ICD), any AEs related to the 
alternate system will be recorded during the course of subject participation, but will not be considered 
related to the EV ICD System. 
Incomplete placement of the lead and/or device, and incomplete or failed electrical or defibrillation 
testing (including prolongation of hospital stay by allowing time to minimize transient factors affecting 
defibrillation) are not considered adverse events; however, any adverse events occurring during an 
unsuccessful implant attempt (e.g., subject allergy to electrodes used during implant) must be recorded 
and classified on an AE eCRF. Unsuccessful EV ICD system implants and/or failed defibrillation testing 
shall be evaluated for reporting as a device deficiency. 
If the EV ICD System is explanted or repositioned after initial implant procedure but prior to pre-
hospital discharge, this shall be captured on a System Modification eCRF.  
8.6. Pre-Hospital Discharge 
Perform the following pre-hospital discharge tests of the EV ICD System at any time after implant, but 
prior to discharge. Prior to the subject being discharged, VF Therapies shall be programmed ON and 
pacing therapies, as appropriate, should be programmed ON.  
Programming requirements and recommendations at PHD are outlined in Table 5. 

 
 
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Table 5: PHD Programming Requirements and Recommendations 
Required Programming 
Recommended Programming 
Initial NID for VF 
Therapies  
Minimum 30/40 
VF Sensing 
Per implant testing 
results (most 
sensitive setting) 
All Rx 
40 J 
VF Sensing if PHD 
Troubleshooting is 
required 
Per PHD testing 
results (most 
sensitive setting) 
Pause Prevention 
Monitor, 5 s 
Post Shock Pacing 
Per physician 
recommendation; 4 V 
margin minimum 
 
 
ATP 
At physician 
discretion; 4 V margin 
minimum 
 
An initial interrogation save-to-media file shall be collected at the beginning of the visit, and a final 
(interrogate all) save-to-media file shall be collected at the end of the visit (see section 8.10). 
 Sensing Testing 
At the Pre-Hospital Discharge visit, perform the Sensing Test in the following postures: 
• 
Sitting 
• 
Supine 
• 
Lying on left 
• 
Lying on right 
Print the Sensing Test Report to PDF or paper and send a copy of the report to Medtronic. 
 Impedance Testing 
Perform the Impedance Test in a sitting posture. If necessary, impedance testing in additional postures 
may be performed. Print the Impedance Test Report to PDF or paper and send a copy of the report to 
Medtronic.  

 
 
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 Pacing Testing 
Perform pacing testing in a supine posture. If necessary, pacing testing in additional postures may be 
performed. The following configurations may be evaluated: Ring1-Coil2, Ring1-Ring2, Coil2-Coil1. 
Pacing capture is defined as at least three consecutive captured beats. 
The clinician will evaluate for pacing sensation during testing. Note: Pacing sensation or discomfort 
observed during testing will not be considered a reportable adverse event.  
If post pace oversensing is observed, sensing parameters should be adjusted to eliminate or minimize 
oversensing. Print the final capture threshold report to PDF or paper and send a copy to Medtronic. 
  Imaging  
Collect the chest radiographs at Prehospital Discharge (PHD) per Table 6 and send to Medtronic (see 
section 8.9). Additional radiographs may be collected at the discretion of the physician at any post-
implant time point if electrical testing at follow-up reveals deterioration in sensing or pacing 
performance.  
Table 6: Chest Radiograph collection during Pre-Hospital Discharge Visit 
Visit 
Image Collection 
Pre-hospital Discharge Visit 
• 
Standing PA → Tidal inhalation breath hold 
• 
Standing LAT → Tidal inhalation breath hold 
Collection of echocardiogram at pre-hospital discharge may be performed per physician discretion, for 
example, if suspicion of potential pericardial effusion exists. 
If additional images (CT scans, radiographs, TEE, MRI or other imaging modalities) are collected at 
physician discretion throughout the duration of the study, it is requested that a copy of the images be 
sent to Medtronic (see section 8.9); these images may be used in the future (e.g., for adverse event 
adjudication, training, education, etc.).  
8.7. Scheduled Follow-up Visits 
Subjects will undergo assessments at scheduled follow-up visits to characterize the safety and efficacy 
of the EV ICD System.  
Medtronic will provide the target dates and windows for each follow-up visit to the implanting site. 
Follow-up visit windows open on the Window Start date and remain open as defined in Table 7. It is 

 
 
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recommended that subjects are scheduled as close as possible to the target date for a given follow-up 
visit. 
Table 7: Scheduled visit windows 
Study Follow-up Visit 
Window 
(Calculated days post-implant procedure) 
Window Start (days 
post-procedure) 
Target (days post-
procedure) 
Window End (days 
post-procedure) 
2 Week 
14 
14 
50 
3 Month 
90 
90 
120 
6 Month 
150 
180 
210 
12 Month (1 Year) 
335 
365 
395 
18 Month 
518 
548 
578 
24 Month (2 Year) 
701 
730 
760 
30 Month 
883 
913 
943 
 
All subjects with an implanted EV ICD System will remain in the study and be followed at pre-defined 
study visits until official study closure. After their study participation ends, the EV ICD System will 
remain implanted and the subject will be provided with standard medical care by their physician. 
At all follow-up visits, photographs of the device pocket and sternal incision are recommended in case 
an infection related to the EV ICD System is suspected or diagnosed. These photographs will not display 
any identifiable features of the subject. The original files will be kept at the hospital and copies will be 
sent to Medtronic. Report any adverse events, including infections, per section 10.5.  
  2-Week Follow-up Visit 
The following data will be collected at the 2-week follow-up visit: 
• 
Electrical Testing (Sensing, Impedance, and Pacing tests (see section 8.7.6) 
• 
Initial (interrogation) and final (interrogate all) save-to-media files (see section 8.10) 
• 
Adverse Event assessment 
• 
Device Deficiencies assessment 
• 
Healthcare Utilizations 
• 
Study Deviations 
• 
Other Cardiac Imaging 

 
 
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• 
Medication Log updates 
 3-Month Follow-up Visit 
The following data will be collected at the 3-month follow-up visit: 
• 
Electrical Testing (Sensing, Impedance, and Pacing tests (see section 8.7.6)) 
• 
Initial (interrogation) and final (interrogate all) save-to-media files (see section 8.10) 
• 
Adverse Event assessment 
• 
Device Deficiencies assessment 
• 
Healthcare Utilizations 
• 
Study Deviations 
• 
Other Cardiac Imaging 
• 
Medication Log updates 
 6-Month Follow-up Visit 
The following data will be collected at the 6-month follow-up visit: 
• 
Electrical Testing (Sensing, Impedance, and Pacing tests (see section 8.7.6)) 
• 
Initial (interrogation) and final (interrogate all) save-to-media files (see section 8.10) 
• 
Adverse Event assessment 
• 
Device Deficiencies assessment 
• 
Healthcare Utilizations 
• 
Study Deviations 
• 
Other Cardiac Imaging 
• 
Medication Log updates 
• 
SF-12 quality of life survey 
If there is evidence for deterioration of electrical performance or significant movement of the lead, the 
clinician may consider either changing the device programming or moving the lead (Note: lead 
repositioning involves a system modification and overall subject health and safety should be 
considered before proceeding) to ensure adequate functioning of the EV ICD System.  

 
 
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 Long-term follow-up Visits 
Subjects will be followed up at 12 months post-implant and every 6 months thereafter until the study is 
closed. The following data will be collected at these visits: 
• 
Electrical Testing (Sensing, Impedance, and Pacing tests; see section 8.7.6) 
• 
Initial (interrogation) and final (interrogate all) save-to-media files (see section 8.10) 
• 
Adverse Event assessment 
• 
Device Deficiencies assessment 
• 
Healthcare Utilizations 
• 
Study Deviations 
• 
Other Cardiac Imaging 
• 
Medication Log updates 
 Device Troubleshooting 
Device troubleshooting is generally required per standard of care for ICD systems and may require 
additional testing. Additional imaging or data collection may be necessary, and a DR220 Digital Holter 
Recorder (North East Monitoring, Inc.; investigational ) may be used for up to 24 hours of Holter 
monitoring. If additional data are collected, data shall be submitted to Medtronic. 
If troubleshooting includes a chronic defibrillation test, it is recommended to follow the steps outlined 
in Appendix H: Chronic Defibrillation Testing Protocol. After conducting a chronic defibrillation test, it is 
required to complete a Chronic Defibrillation Testing eCRF.   
 Electrical Testing 
Subjects’ medical records shall be made available prior to performing electrical testing. An initial 
interrogation save-to-media file shall be collected at the beginning of the visit, and a final (interrogate 
all) save-to-media file shall be collected at the end of the visit (see section 8.10).    
8.7.6.1. Sensing Testing 
At the 2-Week, 3-Month, 6-Month, and Long-Term follow up visits, perform the Sensing Test in a sitting 
posture. If necessary, sensing testing in additional postures may be performed. Print the Sensing Test 
Report to PDF or paper and send a copy of the report to Medtronic.  

 
 
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8.7.6.2. Impedance Testing 
At the 2-Week, 3-Month, 6-Month, and Long-Term follow up visits, perform the Impedance Test in a 
sitting posture. If necessary, impedance testing in additional postures may be performed. Print the 
Impedance Test Report to PDF or paper and send a copy of the report to Medtronic.  
8.7.6.3. Pacing Testing  
At the 2-Week, 3-Month, 6-Month, and Long-Term follow up visits, perform pacing testing in a sitting 
posture. If necessary, pacing testing in additional postures may be performed. The following 
configurations may be evaluated: Ring 1-Coil2, Ring1-Ring2, Coil2-Coil1. Pacing capture is defined as at 
least three consecutive captured beats. If post pace oversensing is observed, sensing parameters 
should be adjusted to eliminate or minimize oversensing. Print the final capture threshold report to 
PDF or paper and send a copy to Medtronic. 
8.8. Unscheduled Visits 
An Unscheduled follow-up visit is defined as any non-standard of care visit by the subject to the 
investigative study site due to the EV ICD System between CIP-required visits.  
If an Unscheduled Visit occurs: 
• 
Document any adverse events and/or device deficiencies on the associated eCRFs, as applicable.  
• 
Where possible, initial (beginning of the visit) and final (end of the visit) device interrogation data 
should be collected via a save-to-media file (see section 8.10).  
• 
If electrical testing is conducted, print the Testing Reports to PDF or paper and send a copy of the 
reports to Medtronic. 
8.9. Images and recordings 
All images and recordings shall be retained in the subject’s file. Copies of images sent to Medtronic 
shall be transferred in DICOM format.  
8.10. Save-to-Media Files  
When a save-to-media file/save-to-media files should be collected, a device interrogation (full 
summary interrogation/interrogate all is best practice) must be performed and saved in a digital format 
(.pdd) on a USB or other removable electronic media. Save-to-media files shall be sent to Medtronic, 

 
 
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with a copy being maintained at the site in the subject’s file. It is recommended that data are not 
cleared during any interrogation. 
8.11. CareLink Transmissions 
It is acceptable to collect and utilize data via CareLink transmissions. A CareLink file collected within a 
visit window will be considered equivalent to an in-office save-to-media file, but a save-to-media file 
for in-office visits is preferred. If review of a CareLink transmission results in a subject visit to the study 
center between scheduled visit windows, an Unscheduled Visit eCRF shall be completed. 
8.12. Healthcare Utilizations 
Health Care Utilization (HCU) information will be collected when the utilizations are related to the 
following characteristics of the EV ICD System: 
• 
All procedure, system, and accessory related adverse events  
• 
Shocks delivered by the EV ICD System (inclusive of inappropriate shocks and appropriate shocks 
delivered to treat ventricular arrhythmias) 
• 
Cardiovascular syncope  
• 
All inpatient hospitalizations, outpatient hospital encounters, emergency department visits, clinic 
visits, urgent care, or rehab center utilizations associated with the characteristics listed above are 
considered reportable HCUs for this study. CIP-required utilizations (except unscheduled visits) 
should not be reported on HCU eCRFs. 
8.13. System Modification 
A System Modification eCRF form shall be completed in the event the EV ICD System requires an 
invasive modification after the subject has been transported out of the procedure room from their 
initial implant (e.g., explant, replacement, repositioning).  
Prior to a system revision a save-to-media file (initial, see section 8.10) shall be collected and the 
physician should consider the following actions: 
• 
Evaluate electrical performance 
• 
Reprogramming 
• 
Imaging (e.g., chest radiographs), images reviewed by the physician shall be sent to Medtronic (see 
section 8.9). 
• 
Elective chronic defibrillation test, it is recommended to follow the steps outlined in Appendix H: 
Chronic Defibrillation Testing Protocol. After conducting a chronic defibrillation test, it is required 
to complete a Chronic Defibrillation Testing eCRF 

 
 
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• 
Risk-benefit to subject   
In the event of a system modification where an EV ICD System remains in the body, the follow up 
schedule for the subject will remain unchanged. In cases where an EV ICD System is explanted and not 
replaced with an EV ICD System, the subject will be exited according to section 8.19.  
If the system modification involves replacing or repositioning the lead, the procedure shall be 
completed by a physician who has undergone EV ICD implant procedure training as specified by 
Medtronic. It is recommended to demonstrate at least a 10J safety margin. Repeat all data collection 
from the PHD visit (see section 8.6), including a final save-to-media file (see section 8.10).     
8.14. Role of the Sponsor Representatives 
Sponsor representatives will provide support as required for the study under supervision of the 
Principal Investigator, including: 
• 
Provide study training, including but not limited to training on the: CIP, Informed Consent 
process, data collection tools, and regulations 
• 
Technical support in installing/uninstalling the programmer software into/from the 
Programmer manually or via the SDN  
• 
Technical support at all study visits under the supervision of the Principal Investigator, 
including device programming, but no data entry on eCRFs shall be performed by Medtronic 
personnel or their representatives at sites 
• 
A trained Medtronic representative may support a study investigator at the Implant Visit by 
proactively providing support and feedback during the implant procedure. 
• 
Sponsor representatives may conduct monitoring and auditing activities for this study. 
Any data collection completed by Medtronic personnel will be clearly identified as such. 
8.15.  Assessment of Efficacy  
Efficacy of the EV ICD System with regards to defibrillation testing success will be assessed per the 
primary efficacy objective at the implant visit (see section 12.4). In addition, efficacy of ATP and shock 
for termination of spontaneous ventricular arrhythmias will be characterized as part of the ancillary 
objectives (see sections 12.5 and 12.9). 

 
 
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8.16.  Assessment of Safety 
Safety of the EV ICD System with regard to major complications related to the system or procedure will 
be assessed by way of the primary safety objective (see section 12.3). All Adverse Events will be 
collected throughout the study duration, starting at the time of signing the Informed Consent Form. 
The prevalence of these adverse events will further be summarized by MedDRA key terms (see section 
12.10). Additionally, any device deficiencies related to the EV ICD system or accessory will be collected. 
Further information on the collection of Adverse Events is discussed in section 10. 
8.17.  Recording Data 
This study will be conducted using an electronic data capture system. The electronic data capture 
system, which allows the study sites to enter study data into the sponsor’s database over a secure 
internet connection, will be used to capture study required eCRF information. The Principal Investigator 
or an individual delegated by the Principal Investigator is responsible for entering data for the study on 
the eCRFs. The Principal Investigator or Sub-Investigator designee (if allowed by local regulation) is 
required to approve all data on eCRFs via electronic signature. The data reported on the eCRFs shall be 
derived from source documents, and any discrepancies shall be explained in writing.  
Save-to-media files will be collected and stored at the site. Copies submitted to Medtronic should be 
sent via secure and compliant electronic file transfer services (e.g., Box) and/or secure mail. 
Programmer printouts will be collected in hard or electronic copy and stored at the site. Copies 
submitted to Medtronic shall be sent via secure and compliant electronic file transfer services (e.g., 
Box) and/or secure mail. 
Fluoroscopy /radiograph/ CT images, if collected, shall be stored on a CD/DVD or USB flash drive at the 
site. Copies submitted to Medtronic shall be sent via secure and compliant electronic file transfer 
services (e.g., Box) and/or secure mail.  
8.18. 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. 
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, rights or well-being of a subject in an emergency or in unforeseen situations 
beyond the investigator’s control (e.g., subject failure to attend scheduled follow-up visit, inadvertent 

 
 
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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 endpoint analysis). 
However, prior approval from Medtronic is required for such situations. 
All study deviations must be reported on an eCRF regardless of whether medically justifiable, pre-
approved by Medtronic, an inadvertent occurrence, or taken to protect the subject in an emergency. In 
the occurrence of a corrupted device interrogation file, Medtronic may request a deviation to 
document that a readable interrogation file is unavailable. 
Refer to section 14.7.2 for deviation reporting requirements and timeframes for reporting to 
Medtronic, Ethics Committee and/or regulatory bodies, as required per local law.  
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 
investigator's participation in the study. Medtronic will provide site-specific reports to investigators 
summarizing information on deviations that occurred at their investigational site on a periodic basis. 
Examples of study deviations include but are not limited to: 
• 
Failure to obtain proper Informed Consent 
• 
Failure to collect required study data (e.g., required imaging) 
• 
Inclusion criteria not met/exclusion criteria met at enrollment 
• 
Missing required save-to-media files 
8.19. Subject Withdrawal or Discontinuation  
Subjects may be exited from the study for reasons such as: 
• 
Subject has completed the study 
• 
Subject lost to follow-up 
• 
Subject death 

 
 
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• 
Subject did not meet inclusion or met exclusion criteria or meets exclusion due to change since 
initial evaluation 
• 
Subject chooses to withdraw (e.g., consent withdrawal, relocation to another geographic 
location) 
• 
Subject does not have or no longer has EV ICD System implanted 
• 
Subject completes but does not pass defibrillation testing prior to pre-hospital discharge 
• 
Investigator deems withdrawal necessary (e.g., medically justified) 
A withdrawn subject will be treated according to standard of medical care and will not be replaced. 
Subjects will be included in the analyses up to the time that consent was withdrawn, or up to the time 
that the subject is exited.  
Subjects who had undergone an implant attempt and did not have an EV ICD System implanted or had 
their EV ICD System removed without replacement with an EV ICD System may be exited by phone at 
the end of 30 days following implant attempt or system removal, or once all system and procedure-
related AEs are resolved.  
The following information is required to be collected at study exit: 
• 
Reason for exit (this shall be documented on the Study Exit eCRF and in the subject’s medical 
record) 
• 
Save-to-media 
In the case that the subject is determined to be lost to follow-up, the investigator will make efforts to 
confirm the vital status/health status of the subject. Details of a minimum of two attempts and the 
method of attempt (e.g., one letter and one phone record or two letters) to contact the subject must 
be recorded. In addition, follow the regulations set forth by the governing Ethics Committee. Upon 
withdrawal from the study, no further study data will be collected, and no additional study visits will 
occur for the subject.  
9. Risks and Benefits 
9.1. Potential Risks 
Medtronic follows rigorous Quality Assurance and Control procedures throughout the development 
and clinical study of a research system. The formal Hazard/ Risk Analysis for the EV ICD System is 
performed according to ISO 14971:2019 (Medical Device Risk Management) and is used to ensure that 
the level of risk is acceptable and reduced as low as possible prior to starting the EV ICD Japan Study. 

 
 
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The EV ICD System is assessed via a System Hazard Analysis to ensure all potential risks, at individual 
component and at system-levels, are evaluated and minimized via risk controls. The subject risk 
assessment evaluates potential risks associated with: system implant/explant, biological compatibility, 
therapy delivery, diagnostic data integrity and security, and potential failure modes associated with the 
finished devices. Risk control strategies for the EV ICD Japan Study risks were developed by a cross-
functional team and in accordance with the Risk Management process. Risk controls are implemented 
via safety design inputs, and acceptable safety performance is demonstrated via system design 
verification and validation activities. During the course of the study, risks will be continuously 
monitored, assessed and documented by the investigators. It is the Principal Investigator’s decision to 
assess whether to continue the study at the respective site, should safety-related concerns arise.   
The risks are reduced as much as possible, with residual risk being documented within the Risk 
Management Report (DSN028279, Revision F or currently approved version) and disclosed in the 
Informed Consent Forms provided to subjects. A summary of the risk analysis and risk assessment will 
also be listed in the EV ICD Pivotal Investigator’s Brochure. 
 
A summary of potential risks and risk mitigation strategies associated with the EV ICD System and EV 
ICD Japan Study is presented in Table 8. Potential risks associated with the study are further minimized 
by selecting qualified investigators and training site personnel on the CIP and hands-on training 
program. 
Table 8: Potential Risks and Mitigation Strategies 
Risks 
Mitigation Strategies 
Procedural risks such as acute trauma, 
infection, or chronic trauma 
i. Procedural technique instructions intended to optimize 
safety are provided in the CIP 
ii. The CIP requires that the EV ICD implant procedure is to 
be performed by an investigator who has received timely 
hands-on training on all aspects of the implant procedure 
iii. Medtronic intends to use a proctorship strategy during 
the EV ICD implant in order to ensure the knowledge and 
skills are transferred to a non-surgical physician specialty 
(EP/Cardiologist). Cardiothoracic surgeons will also provide 
emergency support during the clinical study. 
Failure to provide effective high 
voltage shock therapy when needed 
by the subject 
i. An external defibrillation system(s) is required to be 
present and ready at all times during the implant 
defibrillation testing procedure. The external defibrillator(s) 

 
 
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Risks 
Mitigation Strategies 
is to be prepared to be used in case of emergency. 
ii. Exclusion of subjects with current implantation of a 
pacemaker, ICD, neurostimulator or any other chronically 
implanted device which delivers current in the body, that 
may interfere with therapy delivery 
iii. Testing during the implant procedure to ensure proper 
system set-up connections and lead integrity  
iv. Defibrillation therapy configuration instructions 
provided in the protocol which help promote optimal 
tachyarrhythmia detection and therapy  
v. EV ICD System design verification and end-to-end system 
design validation ensuring defibrillation therapy as 
specified  
Inappropriate delivery of high voltage 
shock therapy 
i. Exclusion of subjects with current implantation of a 
pacemaker, ICD, neurostimulator or any other chronically 
implanted device which uses current in the body, that may 
interfere with therapy delivery 
ii. Testing during the implant procedure to ensure proper 
system set-up connections and lead integrity 
iii. Defibrillation therapy configuration instructions 
provided in the protocol and training which help avoid 
oversensing and resulting inappropriate therapy delivery 
iv. EV ICD System design verification and end-to-end system 
design validation ensuring defibrillation therapy as 
specified 
Failure to provide effective 
bradycardia pacing therapy when 
needed by the subject 
i. Exclusion of subjects with current implantation of a 
pacemaker, ICD, neurostimulator or any other chronically 
implanted device which delivers current in the body, that 
may interfere with therapy delivery 
ii. Testing during the implant procedure to ensure proper 
system set-up connections and lead integrity 
iii. Pacing therapy configuration instructions provided in the 
CIP and training which help avoid oversensing and resulting 
failure to deliver pacing therapy when needed (e.g., post-
shock) 

 
 
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Risks 
Mitigation Strategies 
iv. EV ICD System design verification and end-to-end system 
design validation ensuring pacing therapy as specified 
Delivery of bradycardia pacing therapy 
at an excessive rate causing symptoms 
i. EV ICD System reliability analysis ensuring freedom from 
failures as specified 
Arrhythmia induction (pacing during 
vulnerable period, proarrhythmic 
pauses, electrical/mechanical 
stimulus) 
i. An external defibrillation system(s) is required to be 
present and ready at all times during the implant 
defibrillation testing procedure. The external defibrillator(s) 
is to be prepared to be used in case of emergency. 
ii. EV ICD System reliability analysis ensuring freedom from 
failures as specified 
Acceleration of an existing 
tachyarrhythmia 
i. Defibrillation therapy configuration instructions provided 
in the protocol and training which help avoid ineffective 
shock therapy and resulting arrhythmia acceleration 
ii. EV ICD System design verification and end-to-end system 
design validation ensuring defibrillation therapy as 
specified 
Extracardiac stimulation 
i. Clinician training and CIP procedures for preventive 
measures regarding pain/ stimulation thresholds, including 
the use of general anesthesia, for the potential discomfort 
or pain associated with the pacing stimulation outputs and 
shocks 
ii. Pacing therapy configuration instructions provided in the 
CIP and training which help avoid unnecessary therapy 
energy delivery such that extracardiac stimulation can be 
minimized/avoided 
iii. EV ICD System design verification and end-to-end system 
design validation ensuring pacing therapy as specified 
Thermal/electrical injury to subject 
tissues 
i. EV ICD System reliability analysis ensuring freedom from 
failures as specified 
Subject exposure to toxic materials 
i. EV ICD System design utilizes materials that have 
sufficient biological compatibility and performance as 
demonstrated by a biocompatibility assessment 
Subject exposure to allergic materials 
i. EV ICD System design utilizes materials that have 
sufficient biological compatibility and performance as 
demonstrated by a biocompatibility assessment 
Product degradation due to bio 
i. EV ICD System design utilizes materials that have 

 
 
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Risks 
Mitigation Strategies 
instability 
sufficient biological compatibility and performance as 
demonstrated by years of successful field performance in 
products using equivalent materials 
Missing or misleading data pertaining 
to diagnostic data or system integrity 
is presented to user 
i. EV ICD System design verification and end-to-end system 
design validation ensuring data corruption monitoring as 
specified 
Catastrophic failure of implanted 
product necessitating procedural 
revision of implanted components 
i. EV ICD System reliability analysis ensuring freedom from 
failures as specified 
ii. EV ICD System design verification and end-to-end system 
design validation ensuring system integrity monitoring 
mechanisms as specified 
Exposure to radiation energy via 
diagnostic imaging modalities 
i. Expected medical practice includes shielding the subject 
against unnecessary radiation exposure during diagnostic 
imaging. 
ii. Practicing as low as reasonably achievable (ALARA) 
principles during the device implantation. 
During travel, subjects may not have 
immediate access to programmers 
with applicable software 
i. Subjects will be provided with subject ID cards. Software 
may be downloaded upon request by contacting subject’s 
doctor or Medtronic. 
 
If a subject becomes pregnant during the study, there may be risks that are not yet known. Radiation 
exposure may cause miscarriage, birth defects or other unforeseen medical conditions. 
There may be other discomforts and risks related to the EV ICD System and/or this study that are not 
foreseen at this time. 
The potential adverse events related to the EV ICD System and procedure and the EV ICD Japan Study 
procedures identified from the risk assessment are listed in Table 9. The additional procedural steps 
beyond traditional ICD implant such as increased radiation due to additional required radiographs and 
the substernal placement of the lead were considered in the creation of this list. 
Table 9: EV ICD System/Procedure- and EV ICD Japan Study-related Potential Adverse Events 
EV ICD System/Procedure-related Potential Adverse Events 
EV ICD Japan Study-related Potential Adverse Events 
Acute tissue trauma 
Acute tissue trauma 
Allergic reaction 
Allergic reaction 

 
 
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EV ICD System/Procedure-related Potential Adverse Events 
EV ICD Japan Study-related Potential Adverse Events 
Bradyarrhythmia 
Cardiac arrest 
Cardiac arrest 
Chronic tissue trauma 
Cardiac inflammation 
Discomfort 
Cardiac perforation 
Dizziness 
Cardiac tamponade 
Dyspnea 
Death 
Hiccups 
Device migration 
Infection 
Discomfort 
Mental anguish* 
Dizziness 
Organ damage (liver, mammary arteries, diaphragmatic arteries) 
Dyspnea 
Pain 
Erosion 
Palpitations 
Extracardiac stimulation 
Radiation sickness 
Failure to provide necessary therapy 
Syncope 
Hematoma 
Tachyarrhythmia 
Haemorrhage 
 
Hemothorax 
 
Hiccups 
 
Hospitalization 
 
Inappropriate shock 
 
Infection 
 
Insulation failure 
 
Lead abrasion 
 
Lead fracture 
 
Lead migration or dislodgement 
 
Lethargy 
 
Mental anguish* 
 
Organ damage (liver, mammary arteries, diaphragmatic arteries) 
 
Pain 
 
Palpitations 
 
Pericardial effusion 
 
Pericarditis 
 

 
 
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EV ICD System/Procedure-related Potential Adverse Events 
EV ICD Japan Study-related Potential Adverse Events 
Pneumothorax 
 
Radiation sickness 
 
Return of cardiac symptoms 
 
Seroma 
 
Syncope 
 
Tachyarrhythmia 
 
Toxic reaction 
 
Wound dehiscence  
 
*Subjects susceptible to frequent shocks despite medical management could develop psychological 
intolerance to an ICD system that might include the following conditions: 
• 
Dependency 
• 
Depression 
• 
Fear of premature battery depletion 
• 
Fear of shocking while conscious 
• 
Fear that shocking capability may be lost 
• 
Imagined shocking (phantom shock) 
9.2. Potential Benefits 
The EV ICD Japan Study provides access to ICD therapy for patients who are unable to receive a 
transvenous system because they have occluded vessels or anatomical anomalies, and for patients that 
can benefit from preservation of cardiac vasculature. For other patients, there is no proven benefit. 
Furthermore, the EV ICD System introduces additional potential benefits as compared to subcutaneous 
ICD systems currently on the market, specifically: 
• 
Better signal to noise ratio from the substernal space as compared to a subcutaneous 
configuration, resulting in better detection/discrimination algorithms for sensing arrhythmias (and 
potentially fewer inappropriate shocks) 
• 
Reduced defibrillation energy required to defibrillate as compared to a subcutaneous 
configuration, resulting in improved battery longevity 
• 
Longer battery longevity and corresponding reduction in adverse events associated with device 
replacement 
• 
Asystole pacing 
• 
Anti-tachycardia pacing 
• 
Smaller device which increases patient comfort and acceptance 

 
 
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The information gained from this study could result in the improved management of patients with the 
EV ICD System. Additionally, information collected from this study may assist in the design of new 
product(s)/therapy(ies) and/or instructions for use. 
9.3. Risk-Benefit Rationale 
The majority of the risks associated with the EV ICD System are similar to the risks associated with 
existing transvenous and subcutaneous ICD systems on the market. The unique risks introduced by the 
EV ICD System include: unique harms associated with procedural complications (e.g., liver laceration, 
cardiac trauma/ tamponade), unique harms associated with defibrillating from a substernal lead 
position (e.g., tissue heating/necrosis), unique harms from chronic lead implant in the substernal space 
(e.g., dislodgment due to absence of fibrosis), and the general risk that the EV ICD System is a novel 
system that is currently being evaluated in a pre-market clinical trial. The results of the System Hazard 
Analysis confirm that the patient risks are reduced as far as possible and the residual risks are deemed 
acceptable. 
The foreseeable benefits of the EV ICD System for patients with occluded vessels or anatomical 
anomalies and for patients that can benefit from preservation of cardiac vasculature include: a 
reduction in procedural risk as compared to transvenous systems, enhanced tachyarrhythmia therapies 
as compared to subcutaneous systems (i.e., improved signal/noise, reduced shock energy, and offering 
of ATP), and improved patient comfort and acceptance due to the smaller size of device as compared 
to subcutaneous systems. Although there is no proven benefit for patients who are able to receive a 
transvenous system, there may be benefits specific to the novel design of the EV ICD System. As 
compared to a transvenous system, the EV ICD System is expected to result in fewer extraction 
complications. Since the EV ICD System avoids implanting a lead in the heart, risks such as: systemic 
infection, embolism, vascular/SVC tears, and lead extraction injuries are expected to be significantly 
reduced or eliminated. 
10. Adverse Events and Device Deficiencies 
Timely, accurate, and complete reporting and analysis of safety information for clinical studies are 
crucial for the protection of subjects. Reporting and analysis of safety data are mandated by regulatory 
authorities. Medtronic has established procedures in conformity with regulatory requirements to 
ensure appropriate reporting of safety information. The study is conducted in accordance with these 
procedures and regulations. 

 
 
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10.1.  Assessment 
 Adverse Events Assessment 
Adverse Event (AE) definitions are provided in Table 10.  All AEs will be collected throughout the study 
duration, starting at the time the Informed Consent Form is signed. For purposes of reporting, events 
shall be captured on an AE eCRF or Non Subject AE eCRF. 
All instances of shocks delivered by the EV ICD will be considered associated with a reportable AE. 
Shocks delivered appropriately to treat a ventricular arrhythmia should be noted as treatment 
delivered within the AE for the ventricular arrythmia(s) experienced.  If shocks are delivered 
inappropriately due to an EV ICD issue, the issue should be reported as the underlying system related 
AE. 
Reporting of these events to Medtronic will occur on an Adverse Event eCRF, including a description of 
AE, date of onset of AE, date of awareness of site, treatment, resolution, assessment of both the 
seriousness and the relatedness to the system and/or procedure. Each AE must be recorded on a 
separate AE Form. Subject deaths are also required to be reported. Refer to section 10.7 for Subject 
Death collection and reporting requirements. 
Documented pre-existing conditions are not considered AEs unless the nature or severity of the 
condition has worsened. Worsening may be identified if there is a change in frequency, associated 
symptoms, or the need for new/additional treatment (e.g., ventricular arrhythmias would be 
considered worsened if there are new associated symptoms or treatment/shock is warranted). 
Unavoidable Adverse Events, listed in Table 10 need not be reported unless the adverse event worsens 
or is present outside the stated timeframe post-implant procedure. Adverse events impacting users or 
other persons are also reportable during the course of the study. 
For AEs that require immediate reporting, initial reporting may be done by phone, fax, or on the eCRF 
by completing as much information as possible. The AE eCRF must be completed as soon as possible. 
 Device Deficiencies Assessment 
Device deficiency information will be collected throughout the study and reported to Medtronic. An DD 
eCRF should be completed for each device deficiency that did not lead to an Adverse Event.   
Note that device deficiencies that result in an adverse device effect (ADE) to the subject should be 
captured as an AE only. Device deficiencies that did not lead to an AE but could have led to a Serious 

 
 
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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. 
Examples of instances that may be considered device deficiencies in the absence of an untoward 
clinical occurrence to the subject may include, but are not limited to: 
• 
Damaged components observed out of packaging 
• 
Unsuccessful EV ICD System implant and/or failed defibrillation testing 
• 
Pervasive/persistent sensing issues occurring outside of device testing 
• 
System placement outside of labeling (e.g., lead in pleural space) 
10.2.  Processing Updates and Resolution 
For any changes in status of a previously reported AE (i.e., change in actions taken, change in outcome, 
change in relatedness), information needs to be updated on or added to the original AE form. All AEs 
must be followed until the AE has been resolved, the subject exits the study, or until study closure, 
whichever occurs first.  
All efforts should be made to continue following subjects until all system or procedure related AEs that 
are not resolved, as classified by the investigator, are resolved.  
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. 
10.3.  Adverse Events and Device Deficiency Definitions 
For the purposes of the clinical report, Medtronic will classify each AE according to ISO 14155:2020. 
Where the definition indicates “device”, it refers to any devices used for clinical study used in the 
study. This might be the device under investigation, or any market released component of the EV ICD 
System or accessory. 
 

 
 
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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 the 
use of investigational medical devices or comparators. 
(ISO 14155:2020 section 3.2) 
Note 4: In Japan, this definition includes events related to the investigational medical 
device, the comparator or the concomitant devices, etc. For this study, any EV ICD 
system components listed in Table 1 is applicable. 
Adverse Device Effect (ADE) 
AE related to the use of an investigational medical device. 
Note 1: This definition includes AEs resulting from insufficient or inadequate 
instructions for use, deployment, implantation, installation, or operation, or any 
malfunction of the investigational medical device. 
Note 2: This definition includes any event resulting from use error or from intentional 
misuse of the investigational medical device. 
Note 3: This includes ‘comparator’ if the comparator is a medical device. 
(ISO 14155:2020section 3.1) 
Note 4: In Japan, this definition includes events related to the investigational medical 
device, the comparator or the concomitant devices, etc. For this study, any EV ICD 
system components listed in Table 1 is applicable. 
Device Deficiency (DD) 
Inadequacy of a medical device with respect to its identity, quality, durability, reliability, 
usability, safety or performance.  
 
Note 1: Device deficiencies include malfunctions, use errors, and inadequacy 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) 
Note 3: In Japan, this definition includes events related to the investigational medical 
device, the comparator or the concomitant devices, etc. For this study, any EV ICD 
system components listed in Table 1 is applicable. 
Relatedness 

 
 
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Procedure Related  
An adverse event that is directly related to the implantation or modification of the EV 
ICD System. 
NOTE: In general, this excludes events that are inherent to any surgical procedure (e.g., 
anesthesia complications, anticoagulation interruption) as well as indirect subsequent 
consequences of the procedure (e.g., reaction to pain medication). 
System Related 
An adverse event that results from the presence or performance of any component of 
the EV ICD System.  
 
Device Related: An adverse event that results from the presence or performance 
(intended or otherwise) of the device. 
 
Lead Related: An adverse event that results from the presence or performance 
(intended or otherwise) of the lead. 
Accessory Related 
An adverse event that results from the presence or performance of the EV ICD System 
accessory. 
 
Sternal Tunneling Tool Related: An adverse event that results from the presence or 
performance (intended or otherwise) of the sternal tunneling tool. 
 
Transverse Tunneling Tool Related: An adverse event that results from the presence or 
performance (intended or otherwise) of the transverse tunneling tool. 
 
Safesheath II Related: An adverse event that results from the presence or performance 
(intended or otherwise) of the SafeSheath II. 
 
Programmer Related: An adverse event that results from the presence or performance 
(intended or otherwise) of the programmer. 
 
Programmer Software Related: An adverse event that results from the presence or 
performance (intended or otherwise) of the programmer software. 
 
MyCareLink Patient Monitor Related: An adverse event that results from the presence 
or performance (intended or otherwise) of the patient monitor. 

 
 
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Not Related 
Relationship to the device or procedures can be excluded when: 
• 
The event is not a known side effect of the product category the device belongs to 
or of similar devices and procedures; 
• 
The event has no temporal relationship with the use of the device or the 
procedures; 
• 
The serious event does not follow a known response pattern to the medical device 
(if the response pattern is previously known) and is biologically implausible; 
• 
The discontinuation of medical device application or the reduction of the level of 
activation/exposure – when clinically feasible – and reintroduction of its use (or 
increase of the level of activation/exposure) do not impact the serious event; 
• 
The event involves a body-site or an organ not expected to be affected by the 
device or procedure; 
• 
The serious event can be attributed to another cause (e.g., an underlying or 
concurrent illness/clinical condition, an effect of another device, drug, treatment, 
or other risk factors); 
• 
The event does not depend on a false result given by the device used for diagnosis 
(when applicable); 
• 
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. 
Unlikely 
The relationship with the use of the device seems not relevant and/or the event can be 
reasonably explained by another cause, but additional information may be obtained. 
Possible 
The relationship with the use of the investigational device is weak but cannot be ruled 
out completely. Alternative causes are also possible (e.g., an underlying or concurrent 
illness/ clinical condition or/and an effect of another device, drug or treatment). Cases 
where 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.  

 
 
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Causal Relationship 
The event is associated with the device or study procedures beyond reasonable doubt 
when: 
• 
The event is a known side effect of the product category the 
device belongs to or of similar devices and procedures; 
• 
The event has a temporal relationship with device 
use/application or procedures; 
• 
The event involves a body-site or organ that the device or 
procedures are applied to or the device or procedures have an 
effect on; 
• 
The serious event follows a known response pattern to the 
medical device (if the response pattern is previously known); 
• 
The discontinuation of medical device application (or reduction 
of the level of activation/exposure) and reintroduction of its use 
(or increase of the level of activation/exposure) impact on the 
serious event (when clinically feasible); 
• 
Other possible causes (e.g., an underlying or concurrent 
illness/clinical condition or/and an effect of another device, 
drug, or treatment) have been adequately ruled out; 
• 
Harm to the subject is due to error in use; 
• 
The event depends on a false result given by the device used for 
diagnosis (when applicable); 
• 
In order to establish the relatedness, not all the criteria listed 
above might be met at the same time, depending on the type of 
device/procedures and the serious event. 
 

 
 
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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, 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 diseases, 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) fetal distress, fetal 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) 
ADE that has resulted in any of the consequences characteristic of a SAE. 
(ISO 14155:2020 section 3.44)  
Unanticipated Serious Adverse Device 
Effect (USADE) 
 
SADE which by its nature, incidence, severity or outcome has not been identified in the 
current risk assessment. 
Note 1: Anticipated Serious Adverse Device Effect (ASADE) is an effect which by its 
nature, incidence, severity or outcome has been identified in the risk assessment. 
(ISO 14155:2020 section 3.51) 
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 section 3.46) 

 
 
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Complication 
An adverse event that includes the following is considered a complication: 
• 
Results in death,  
• 
Involves any termination of significant device function (i.e., defibrillation 
therapy), or  
• 
Requires an invasive intervention 
Non-invasive (21 CFR 812.3(k)): 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 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. 
 
For purposes of this part, blood sampling that involves simple venipuncture is 
considered non-invasive, 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 
non-invasive. 
 
Note: Only system or procedure related AEs will be classified as complication (major, 
minor) or observation. 
Major complication 
A system or procedure-related complication which results in: 
• 
Death 
• 
Permanent loss of defibrillation function due to mechanical or electrical 
dysfunction of the device  
• 
Hospitalization 
• 
Prolongation of an existing hospitalization by at least 48 hours  
• 
System revision (reposition, replacement, explant) 
 
Note: Only system or procedure related AEs will be classified as complication (major, 
minor) or observation. 
Minor complication 
Any complication that is not a major complication (e.g., event classified as a 
complication solely based on intravenous drug administration). 
 
Note: Only system or procedure related AEs will be classified as complication (major, 
minor) or observation. 
Observation 
Any adverse event that is not a complication. 
 
Note: Only system or procedure related AEs will be classified as complication (major, 
minor) or observation. 
Timing 
Pre-Implant Procedure 
Occurs after the IC has been signed but before the skin incision during the EV ICD 
implant procedure. 

 
 
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During Implant Procedure 
Occurs during the EV ICD implant procedure, after skin incision and prior to completion 
of skin closure. 
Post-Implant Procedure 
Occurs after the completion of skin closure for the EV ICD implant procedure. 
Other 
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:  
Event Description 
Timeframe (hours) 
from the Surgical 
Procedure 
Anesthesia related nausea / vomiting  
24 
Low-grade fever (oral temperature >98.6°F 
(>37°C) but <100.4°F (<38.0°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 
Hospitalization 
A therapeutic inpatient hospitalization (excludes observation unit, emergency room and 
outpatient visits) lasting greater than or equal to 24 hours. 
10.4.  Adverse Event and Deficiency Classification 
All adverse events and device deficiencies will be reviewed by a Medtronic representative. AEs will be 
classified according to the definitions provided in section 10.3.  
Upon receipt of AEs at Medtronic, a Medtronic representative will review the adverse event/device 
deficiency for completeness and accuracy and, when necessary, will request clarification and/or 
additional information from the Investigator. Medtronic will utilize MedDRA, the Medical Dictionary for 
Regulatory Activities, to assign a MedDRA term for each AE based on the information provided by the 
investigator.  
Regulatory reporting of AEs and device deficiencies that could have led to a SADE will be completed 
according to local regulatory requirements. Refer to section 14.7 for a list of additional required 
investigator and Medtronic reporting requirements and timeframes. It is the responsibility of the 
investigator to abide by any additional AE reporting requirements stipulated by the Ethics Committee 
responsible for oversight of the study. 

 
 
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For a list of Foreseeable Adverse Event List, refer to Appendix D: Foreseeable Adverse Event List. The 
Foreseeable Adverse Event List consists of observed adverse device effects in similar Medtronic 
studies, adverse events reported in published literature and other special considerations. An evaluation 
of potentially anticipated events, adverse device effects observed in previous clinical studies, and 
reported events in literature may be used in combination with device labeling, current event reporting 
information, and other published data to assess if an adverse event is unexpected. 
Adverse Events and Deaths will be classified according to the standard definitions as outlined in Table 
11. 
Table 11: Adverse Event classification responsibilities 
What is classified  Who classifies 
Classification Parameters 
Timing of the Event 
Investigator 
Pre-implant procedure, During implant procedure, Post-
implant procedure 
Relatedness 
 
Investigator 
Procedure, Device, Lead, Sternal Tunneling Tool, 
Transverse Tunneling Tool, SafeSheath II, Programmer, 
Programmer Software, Patient Monitor 
Sponsor 
Procedure, Device, Lead, Sternal Tunneling Tool, 
Transverse Tunneling Tool, SafeSheath II, Programmer, 
Programmer Software, Patient Monitor 
Seriousness 
Investigator 
SAE, Device Deficiency with SADE potential 
Sponsor 
SAE, USADE, Device Deficiency with SADE potential 
Diagnosis 
Investigator 
Based on presenting signs and symptoms and other 
supporting data 
Sponsor 
MedDRA term assigned based on the data provided by 
Investigator 
Death Classification Investigator 
Sudden Cardiac, Non-sudden Cardiac, Non-Cardiac, 
Unknown 
 
An independent Clinical Events Committee (CEC) will review and adjudicate, at a minimum, all events 
classified by the investigator or Medtronic as procedure or system related to determine relatedness 
and complication (major, minor) or observation classifications. In addition, the CEC will also review and 
adjudicate all Adverse Events resulting in death. 
When determining whether a USADE has occurred, where the sponsor’s causality assessment conflicts 
with the assessment made by the site investigator, the site investigator’s assessment cannot be 
downgraded by the sponsor (i.e., altered from ‘related’ to ‘not related’). In this case, if an investigator’s 

 
 
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judgment triggers the reporting of a USADE, the opinion of both the investigator and the sponsor 
should be provided with any report sent to regulatory reporting as required. 
10.5.  Reporting of Adverse Events 
Adverse events and Device Deficiencies will be reported according to local regulatory requirements. It 
is the responsibility of the investigator to abide by the AE/DD reporting requirements stipulated by 
local law and the Ethics Committee. Reporting requirements in Table 12 have been summarized at the 
time of CIP creation; however, changes may occur during the course of the study.  It is the 
investigator’s responsibility to comply with current reporting requirements.  
Refer to section 14.7 for a list of additional required investigator and Medtronic reporting 
requirements and timeframes.  
For AEs/DDs that require immediate reporting, initial reporting may be done by contacting the study 
sponsor per the sponsor contact information provided in this document. For emergency contact 
regarding a USADE, SAE and/or SADE, contact a clinical study representative immediately (refer to the 
study contact list provided in the site’s study documents binder/investigator site file or refer to the 
contact information provided on the title page).   

 
 
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Table 12: Adverse Event Reporting Requirements 
Serious Adverse Events (SAEs) 
Investigator submit to: 
Medtronic 
Immediately (no later than 72 hours) (Japan GCP Article 68) 
Investigators 
Head of Medical Institution 
(HOMI) 
Submit per IRB reporting requirements 
Sponsor submit to: 
Investigators 
As for individual report, report to Head of Medical Institution and PI immediately. Head of Medical 
Institution of each site request the IRB to deliberate them. Or, report to Head of Medical Institution, 
PI and IRB chairman immediately if needed. 
Serious Adverse Device Effects (SADEs) 
Investigator submit to: 
Medtronic 
Immediately (no later than 72 hours) (Japan GCP Article 68) 
HOMI 
Immediately (Japan GCP Article 68) 
Sponsor submit to: 
Regulatory authorities 
[Life threatening or death] Individual reporting within 15 calendar days after awareness, and [All 
SADEs] Annually (Enforcement Regulation of the PMDL Article 274- 2) 
Investigators 
HOMI 
As for individual report, report to Head of Medical Institution and PI immediately. Head of Medical 
Institution of each site request the IRB to deliberate them. Or, report to Head of Medical Institution, 
PI and IRB chairman immediately if needed. 
As for periodical report, report to Head of Medical Institution and PI annually. Head of Medical 
Institution of each site request the IRB to deliberate them. Or, report to Head of Medical Institution, 
PI and IRB chairman annually if needed. 
Unanticipated Serious Adverse Device Effects (USADEs) 
Investigator submit to: 
Medtronic 
Immediately (no later than 72 hours) (Japan GCP Article 68) 
HOMI 
Immediately (Japan GCP Article 68) 
Sponsor submit to: 
Regulatory authorities 
[Life-threatening or death) Individual reporting within 7 calendar days after awareness, [Non-life 
threatening or death) Individual reporting within 15 calendar days after awareness, and [All USADE] 
Annually.  (Enforcement Regulation of PMDL Article 274-2) 
Investigators 
HOMI 
Immediately (Japan GCP Article 28) 
Device Deficiencies with SADE potential 
Investigator submit to: 
Medtronic 
Immediately (no later than 72 hours) (Japan GCP Article 68) 
HOMI 
Submit per IRB reporting requirements 
Sponsor submit to: 
Regulatory authorities 
Within 30 calendar days after awareness and annually (Enforcement Regulation of PMDL Article 274-
2) 

 
 
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Investigators 
HOMI 
Immediately per the direction of PMDA and/or annually (Japan GCP Article 28) 
10.6. Subject Death 
All subject deaths must be reported by the investigator to Medtronic on an AE eCRF (AE with fatal 
outcome) as soon as possible after the investigator first learns of the death. In case of death, there 
should be one SAE with an outcome of fatal. 
A de-identified copy of the death certificate, should be sent to the Medtronic clinical study team. 
When a death occurs in a hospital, a copy of the death summary report and all relevant hospital 
records should be sent to Medtronic, if available. If an autopsy is conducted, the autopsy report should 
also be sent to Medtronic. When the death occurs at a remote site, it is the investigative site’s 
responsibility to attempt retrieval of information about the death. In summary, the following data will 
be collected: 
• 
Date of death 
• 
Detailed description of death 
• 
Cause of death 
• 
Relatedness to system and/or procedure 
• 
Device interrogation (if available) 
• 
Death summary/hospital records (if available) 
• 
Autopsy report (if available) 
• 
Death certificate (if available) 
10.7.  Death Classification and Reporting 
Sufficient information will be required in order to properly classify the subject’s death. The Investigator 
shall classify each subject death per the following definitions: 
Cardiac Death: A death directly related to the electrical or mechanical dysfunction of the heart. 
• 
Sudden Cardiac Death (SCD): Natural death due to cardiac causes, indicated by abrupt loss of 
consciousness within one hour of the onset of acute symptoms; preexisting heart disease may 
have been known to be present, but the time and mode of death are unexpected. If time of 
onset cannot be determined, SCD will 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. 

 
 
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Unknown Cardiac Classification: Unknown death classification is intended for use only when there is 
insufficient or inadequate information to classify the death. 
The Clinical Events Committee will also review all deaths and provide an adjudication of the death 
classification. See section 11.1 for handling events where the adjudication of the investigator and the 
CEC differ. 
10.8.  Product Complaint Reporting 
The reporting of product complaints is not part of the EV ICD Japan Study and should be done in 
addition to the AE/DD reporting requirements.  It is the responsibility of the investigator to report all 
product complaints associated with a medical device distributed by Medtronic, regardless of 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.   
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. 
11. Data Review Committees  
11.1.  Clinical Events Committee 
The study will utilize an independent Clinical Events Committee (CEC). At regular intervals, an 
independent CEC will review events and adjudicate at a minimum all system and procedure-related 
events. Additionally, the CEC will provide an adjudication of the death classification for all reported 
deaths.  
The CEC will consist of a minimum of three (3) non-Medtronic-employed physicians whose site is not 
participating in the study, including a CEC chairperson.  
Medtronic personnel may facilitate and participate in CEC meetings but will be non-voting members. 
For AEs and deaths reviewed by the CEC, Medtronic will provide the CEC with the Investigator’s 
description and supportive documentation (when available). The CEC is responsible for reviewing the 
Investigator’s description and supportive documentation (when available), reviewing applicable 
definitions, and determining final classifications for all adjudication parameters. For AEs, classification 
includes system/procedure relatedness and complication (major, minor) or observation. Additionally, 

 
 
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the CEC will provide an adjudication for all reported deaths, including system/procedure relatedness 
and cardiac relatedness. 
If the CEC disagrees with the investigator’s classification of the event, the difference will be provided to 
the investigator. If the investigator agrees with the CEC’s adjudication, the eCRF 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 ethics committees and regulatory authorities, if 
required. 
11.2. Episode Review Committee 
An Episode Review Committee (ERC) will be established to evaluate device-treated ventricular episodes 
according to an ERC Charter. Committee membership, meeting frequency, roles and responsibilities 
and procedures will also be described in the ERC Charter. Device-treated ventricular episodes in the 
device episode log with EGM will be reviewed by the ERC and adjudicated based on appropriateness of 
therapy (shocks and ATP) delivered to subjects and success of the therapy. Inappropriate therapy will 
be identified based on adjudication rhythm truth and device episode log information.  
This committee may include independent physicians and/or Medtronic personnel. The ERC Member list 
will be under a separate cover and available upon request. 
12. Statistical Design and Methods 
12.1.  General Considerations  
Data analysis will be performed by a Medtronic statistician or designee. 
The cohort will include all enrolled subjects who undergo the study procedures unless the subject does 
not complete the required testing, and there are no pre-specified subgroups for assessment. For 
endpoints involving only measurements collected at follow-up visits, only subjects who complete those 
visits will be included in the analysis of those endpoints. 
A Statistical Analysis Plan will be developed and kept under separate cover and will include a 
comprehensive description of the statistical methods and reports to be included in the final study 
report, as well as a description of how missing, unused, and spurious data will be accounted. Any 
change to the data analysis methods described in the CIP will require an amendment only if it changes 

 
 
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a principal feature of the CIP. Any other change to the data analysis methods described in the CIP, and 
the justification for making the change, will be described in the clinical study report. 
12.2. Sample Size  
About 15 and up to 25 subjects will be implanted with the investigational EV ICD system. Enrollment is 
stopped once 15 subjects have completed the defibrillation protocol testing at implant;but any 
previously scheduled implant procedures would be allowed to occur. There are no hypotheses for both 
primary safety and efficacy objectives in this study. The sample size is not pre-specified to satisfy any 
statistical requirements, but rather to allow for multiple investigational sites enrolling patients and 
implanting the EV ICD system. 
12.3.  Primary Objective #1: Safety 
Characterize the freedom from major complications related to the EV ICD System and/or procedure at 
2 weeks post-implant.  
 Hypothesis 
There are no hypotheses for this objective. 
 Performance Requirements 
Performance requirements are not pre-specified for this objective. The endpoint is defined as a 
subject’s first occurrence of a major complication related to the EV ICD System and/or procedure as 
determined by the independent Clinical Event Committee (CEC) that occurs on or prior to 2-weeks (14-
days) post-implant. 
For an adverse event to meet the endpoint, the event must have occurred within 14 days (inclusive) of 
the EV ICD System implant attempt and be adjudicated by the CEC as being a major complication 
related to the EV ICD System and/or procedure. Major complications are those complications resulting 
in: 
• 
Death 
• 
Permanent loss of defibrillation function due to mechanical or electrical dysfunction of the 
device  
• 
Hospitalization (see Table  for Hospitalization definition) 
• 
Prolongation of an existing hospitalization by at least 48 hours 
• 
System revision (reposition, replacement, explant) 

 
 
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 Rationale for Performance Criteria 
This objective is for the purpose of gathering data pertaining to device safety over the first 2 weeks 
post-implant.  There are no pre-specified performance criteria. 
 Analysis Methods 
Results will be summarized in aggregate using descriptive statistics. The 14-day freedom from major 
complication rate will be calculated using the Kaplan-Meier method, and the total number of major 
complications experienced by subjects for whom an implant is attempted will be summarized.  
 Determination of Subjects/Data for Analysis 
All subjects with an implant attempt of the investigational product will be included in the analysis. 
12.4.  Primary Objective #2: Efficacy  
Characterize the EV ICD defibrillation testing success rate at implant. 
 Hypothesis 
There are no hypotheses for this objective. 
  Performance Requirements 
Performance requirements are not pre-specified for this objective. The endpoint, defibrillation testing 
success, is defined as: 
• 
Single SSVA conversion at 20J, or  
• 
Conversion of two consecutive episodes of SSVA at 30J in final system configuration. 
Notes: 
• 
In one of the two consecutive SSVA episodes, up to two 30J shocks are permitted. 
• 
To achieve final system configuration, changing the position of the ICD generator and/or the lead 
or changing shock polarity is permitted. 
• 
Subjects can return for testing on another day if testing is not fully completed on the day of 
implant. 

 
 
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 Rationale for Performance Criteria 
This objective is for the purpose of gathering data pertaining to defibrillation efficacy at implant.  There 
are no pre-specified performance criteria. 
 Analysis Methods 
Results will be summarized in aggregate using descriptive statistics. Subjects will be partitioned by the 
results of their defibrillation testing (e.g., no rescue shocks required, one rescue shock required), with 
counts and percentage falling into each subgroup reported. Each subject who completes the 
defibrillation protocol will be determined to either have successfully met the defibrillation endpoint or 
not met the endpoint. The EV ICD defibrillation testing success rate at implant will be calculated as the 
proportion of subjects who successfully met the defibrillation endpoint.  
 Determination of Subjects/Data for Analysis 
All subjects who complete the defibrillation protocol will be included in the analysis. 
12.5.  Ancillary Objective #1  
Characterize appropriate and inappropriate shocks. 
 Hypothesis 
There are no hypotheses for this objective.  Spontaneous episodes receiving shocks will be 
summarized.  
  Performance Requirements 
Performance requirements are not pre-specified for this objective. The endpoint is defined as a shock 
delivered by the EV ICD. Spontaneous arrhythmic episodes resulting in a shock will be adjudicated to 
determine the underlying rhythm.  
 Rationale for Performance Criteria 
Due to the minimal number of appropriate and inappropriate shocks expected for spontaneous 
arrhythmias, this objective is intended to only characterize device performance with regard to sensing 
ventricular arrhythmias and delivering shocks when the episode either does not self-terminate or is not 
terminated by ATP. There are no pre-specified performance criteria. 

 
 
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 Analysis Methods 
Results will be summarized in aggregate using descriptive statistics. All shocks delivered by the device 
for spontaneous arrhythmias will be partitioned by whether the treated rhythm was a VT/VF episode, 
and by the specific rhythm of the episode. Both the number of episodes and the number of subjects 
experiencing such episodes will be reported, as well as the energy delivered.  Kaplan-Meier curves for 
time to first appropriate shock and time to first inappropriate shock may be provided to demonstrate 
shock incidence. 
 Determination of Subjects/Data for Analysis 
All subjects successfully implanted with an EV ICD having at least one device interrogation post-implant 
will be included in the analysis. At minimum, all episodes occurring by the date at which all implanted 
subjects have had the opportunity to be followed for 2 weeks post-implant will be included. 
12.6.  Ancillary Objective #2 
Characterize electrical performance (pacing capture thresholds, pacing impedance, sensing amplitudes) 
over time. 
 Hypothesis 
There are no hypotheses for this objective. Pacing capture performance, as well as pacing impedance 
and sensing amplitudes, will be summarized. 
  Performance Requirements 
Performance requirements are not pre-specified for this objective. The endpoints are defined as pacing 
capture threshold, pacing impedance, and sensing amplitude. The pacing testing will be performed at 
pre-hospital discharge, as well as visits at 2 weeks, 3- and 6-months post-implant and every 6 months 
thereafter.  
 Rationale for Performance Criteria 
This objective is for the purpose of characterizing device performance with regard to achieving pacing 
capture and determining sensing performance over time. There are no pre-specified performance 
criteria. 

 
 
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 Analysis Methods 
Results will be summarized in aggregate using descriptive statistics.  For each follow-up visit, the 
proportion of subjects undergoing pacing testing will be reported, as well as the proportion for whom 
capture is obtained. Mean impedance and R-wave amplitudes will also be reported at each follow-up 
for which the testing occurs (pre-hospital discharge, 2 weeks, 3- and 6-months post-implant, and every 
6 months thereafter). 
 Determination of Subjects/Data for Analysis 
All subjects successfully implanted with an EV ICD having relevant data (pacing tests, impedance, 
sensing amplitudes) will be included in the analysis of that endpoint at that timepoint. 
12.7.  Ancillary Objective #3  
Characterize extracardiac pacing sensation. 
 Hypothesis 
There are no hypotheses for this objective.  
  Performance Requirements 
Performance requirements are not pre-specified for this objective. The endpoint will be defined as 
whether pacing therapies were programmed OFF due to pacing sensation. 
 Rationale for Performance Criteria 
There are no pre-specified performance criteria; pacing sensation at follow-up will be summarized and 
reported. 
 Analysis Methods 
Results will be summarized in aggregate using descriptive statistics. Descriptive statistics will be used to 
summarize distribution among the subjects who completed each follow-up visit, and whether pacing 
therapies, specifically ATP, were programmed OFF due to the subject reporting pacing sensation. This 
objective will be analyzed using data from the pre-hospital discharge, 2 weeks, 3- and 6-month, and 
long-term visits. 

 
 
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 Determination of Subjects/Data for Analysis 
For each visit (e.g., PHD, 2 weeks), all subjects successfully implanted with an EV ICD who complete 
that visit will be included in the analysis.     
12.8.  Ancillary Objective #4 
Characterize asystole pacing.  
 Hypothesis 
There are no hypotheses for this objective, as the purpose of this objective is simply to characterize 
prevalence of asystole pacing in this population.  
  Performance Requirements 
Performance requirements are not pre-specified for this objective. The endpoint is the amount of 
pacing for asystole the subject received.  
 Rationale for Performance Criteria 
This objective is for the purpose of characterizing prevalence of need for asystole pacing in this 
population. There are no pre-specified performance criteria. 
 Analysis Methods 
Descriptive statistics will be used to summarize the number of subjects and amount of asystole pacing 
experienced during follow-up.   
 Determination of Subjects/Data for Analysis 
All subjects successfully implanted with an EV ICD with at least one device interrogation post-implant 
will be eligible for the analysis. At minimum, all instances occurring on or before the date at which all 
implanted subjects have had the opportunity to be followed for 2 weeks post-implant will be included. 
12.9. Ancillary Objective #5 
Summarize ATP performance with spontaneous arrhythmias. 

 
 
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 Hypothesis 
There are no hypotheses for this objective, as the purpose is to characterize defibrillation performance 
through use of ATP.  
  Performance Requirements 
Performance requirements are not pre-specified for this objective.  The endpoint is defined as whether 
a spontaneous ventricular tachycardia episode for which ATP was delivered by the EV ICD was 
terminated by ATP. Spontaneous arrhythmias will be adjudicated to determine the underlying rhythm 
and whether they were terminated by ATP.  
 Rationale for Performance Criteria 
It is projected that only a small subset of implanted subjects may experience one or more ventricular 
arrhythmias during follow-up. Therefore, device performance regarding such episodes will be 
characterized only.  There are no pre-specified performance criteria. 
 Analysis Methods 
Results will be summarized in aggregate using descriptive statistics. All monomorphic and polymorphic 
ventricular arrhythmias with EGM will be partitioned by whether the treated rhythm received ATP 
and/or shock, whether it successfully terminated as a result, and by the specific rhythm of the episode 
(monomorphic vs. polymorphic VT/VF). Both the number of episodes and the number of subjects 
experiencing such episodes will be reported, as well as the percentage of monomorphic VT episodes 
successfully terminated by ATP. 
 Determination of Subjects/Data for Analysis 
All subjects successfully implanted with an EV ICD having at least one device interrogation post-implant 
will be included in the analysis. At minimum, all VT/VF episodes occurring on or prior to the date by 
which all implanted subjects have had the opportunity to be followed for 2 weeks post-implant will be 
included in the analysis.  
12.10. Ancillary Objective #6 
Summarize adverse events. 

 
 
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 Hypothesis 
There are no hypotheses for this objective, as safety of the EV ICD System is being evaluated by Primary 
Objective #1 (see section 12.3).  This objective is to provide a comprehensive summary of adverse 
events experienced during follow-up.  
 Performance Requirements 
Performance requirements are not pre-specified for this objective. The endpoint is an adverse event 
(see Table  for definition of adverse event) experienced by a subject post-enrollment and prior to exit. 
Adverse events will be adjudicated by a Clinical Events Committee for relatedness to the EV ICD System 
and procedure.  
 Rationale for Performance Criteria 
This objective is for the purpose of gathering comprehensive data pertaining to subject health over at 
least the first two weeks post-implant. There are no pre-specified performance criteria. 
 Analysis Methods 
Results will be summarized in aggregate using descriptive statistics. Counts and percentages of subjects 
experiencing system and/or procedure-related adverse events will be reported, as well as, in the case 
of system-related events, the specific component of the system to which the event was related. 
Adverse Events will be broken out by MedDRA keyterm, with both counts of events and counts of 
subjects experiencing each type of event reported. 
 Determination of Subjects/Data for Analysis 
All subjects for whom an implant of the investigational product is attempted will be included in the 
analysis. At minimum, all adverse events recorded by the date by which all implanted subjects have 
been followed at least 2 weeks post-implant will be included. 
12.11. Ancillary Objective #7 
Characterize EV ICD defibrillation testing conducted per physician discretion.  
 Hypothesis 
No statistical hypotheses will be tested for this objective. 

 
 
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 Performance Requirements 
Chronic defibrillation testing per physician discretion may occur as a part of device troubleshooting or 
after a system modification. According to section 8.7.5, if device troubleshooting includes a chronic 
defibrillation test, it is recommended to follow the steps outlined in Appendix I: Chronic Defibrillation 
Testing Protocol. According to section 8.13, if a system modification involves replacing or repositioning 
the lead, it is recommended to demonstrate at least a 10J safety margin.   
Performance requirements are not pre-specified for this objective.  
 Rationale for Performance Criteria 
Chronic defibrillation testing is rarely done as standard of care, and no single testing protocol is 
required for chronic testing. There are no performance criteria for this objective.  
 Analysis Methods 
Results will be summarized in aggregate using descriptive statistics.  Subjects will be partitioned by the 
results of their defibrillation testing (e.g., no rescue shocks required, one rescue shock required), with 
counts and percentage falling into each subgroup reported.   
 Determination of Subjects/Data for Analysis 
All subjects for whom chronic defibrillation testing is attempted per physician discretion will be 
included in the analysis. 
12.12. Supplemental Analysis 
Quality of Life/patient acceptance will also be measured through the SF-12 Questionnaire at baseline 
and 6 months. The tool will be administered so that subject response in this study may be compared to 
response to such tools in other ICD studies. 
13. Ethics 
13.1.  Statement(s) of Compliance  
The study will be conducted according to the Declaration of Helsinki, CIP, Good Clinical Practice (GCP) 
and in accordance to the national and local laws, regulations, standards, and requirements. The 
principles of the Declaration of Helsinki are implemented in this study by means of the Informed 

 
 
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Consent process, Ethics Committee approval, study training, clinical trial registration, and risk benefit 
assessment. 
The clinical investigation shall not begin until all required approvals and documents from the Ethics 
Committee and regulatory authorities, if needed, have been received. Any additional requirements 
imposed by the Ethics Committee or regulatory authority shall be followed, if appropriate. 
This EV ICD Japan Study will be conducted in compliance with international ethical and scientific quality 
standards, known as good clinical practice (GCP). GCP includes review and approval by an independent 
Ethics Committee before initiating a study, continuing review of an ongoing study by an Ethics 
Committee, and obtaining and documenting the freely given Informed Consent of a subject before 
initiating the study. 
The EV ICD Japan Study is 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.  Adverse 
Event and Device Deficiency handling in the EV ICD Japan Study is ISO 14155:2020 compliant for all 
participating geographies. 
Ultimately, all sites will follow and comply with: 
• 
The Clinical Trial Agreement 
• 
The procedures described within this CIP 
• 
Local Ethics Committee Requirements 
In addition to the 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 the following:  
In Japan, the study will be conducted in compliance with: 
 
• 
Ministerial Ordinance Concerning Good Clinical Practice for Medical Devices (The Ministry of 
Health, Labour and Welfare (MHLW) Ministerial Ordinance No.36 in 2005 revised on 26 Oct 2017) 
• 
21 CFR Part 11: Electronic Records, Electronic Signatures 
• 
Principles of Declaration of Helsinki and all of its subsequent amendments, including the latest 
version 2013 

 
 
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The study will be publicly registered prior to first enrollment in accordance with Declaration of Helsinki 
on jRCT (https://jrct.niph.go.jp/).  
Approval of the CIP and CIP amendments, if applicable, is required from the following groups prior to 
any study procedures at a study site: 
• 
Medtronic 
• 
Principal Investigators  
• 
Regulatory Authorities 
• 
Ethics Committees 
Similarly, approval of subsequent revisions to the CIP is required from the above-mentioned groups 
prior to implementation of the revised CIP at each study site. 
14. Study Administration 
14.1.  Monitoring 
It is the responsibility of Medtronic to ensure proper monitoring of this clinical study. Trained 
Medtronic personnel or delegates appointed by Medtronic may perform study monitoring at the study 
site to ensure the study is conducted in accordance with the CIP, the Clinical Trial Agreement, and 
applicable regulatory and local requirements. Medtronic, or delegates, must therefore have access to 
the subjects’ case histories (clinic and hospital records, and other source data/documentation) upon 
request as per the Informed Consent Form, Authorization to Use and Disclose Personal Health 
Information/Research Authorization/ other privacy language (where applicable) and Clinical Trial 
Agreement. The Principal Investigator should also be available during monitoring visits. 
Frequency of monitoring visits may be based upon subject enrollment, duration of the study, study 
compliance, number of adverse events, number of deviations, findings from previous monitoring visits 
and any suspected inconsistency in data that requires investigation. 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 in accordance with the study monitoring plan to assess 
site study progress, the investigator’s adherence to the CIP, regulatory compliance including but not 
limited to Ethics Committee approval and review of the study, maintenance of records and reports, 
and review of source documents against eCRFs. Monitors review site regulatory and study compliance 
by identifying findings of non-compliance and communicating those findings along with 

 
 
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recommendations for preventative/corrective actions to 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 site. 
14.2.  Data Management 
Data will be collected using an electronic data management system for clinical studies.  Electronic Case 
Report Form (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 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 by Medtronic. 
 
The data reported on the eCRFs shall be derived from source documents and be consistent with these 
source documents.  Source documents, which may include patient medical records, device interrogation 
files, programmer printouts, and worksheets, must be created and maintained by site personnel. The 
eCRF may be considered as source for the following data points: 
• 
Adverse Event: date site became aware of event  
• 
Non-Subject Adverse Event: date site became aware of event  
• 
Device Deficiency: date site became aware of deficiency  
• 
Protocol Deviation: reason for deviation 
• 
EV ICD Device Accountability eCRFs: 
o DVEX3E4 EV ICD (except for date used/date explanted) 
o EV2401 EV ICD Lead (except for date used/date explanted) 
o EAZ101 and EAZ201 Tunneling Tools (except for date used) 
o Oscor SafeSheath® II Model SSCL9 introducer (except for date used) 
o SW041 Programmer Software 
o DR220 NorthEast Monitoring Digital Holter Recorder 
o Medtronic MyCareLink Patient Monitor 
Device data from transmissions provided to Medtronic will be uploaded to secure servers and made 
accessible to the study team. Save-to-media files and other non-eCRF data such as Radiographs and 
Fluoroscopies collected via electronic media at office visits may be sent to Medtronic. Upon receipt via 
transmission or electronic media, non-eCRF data will be securely maintained, and stored, and retrieved 
for analysis and reporting. 

 
 
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14.3. Direct Access to Source Data/Documents  
The sponsor or a regulatory authority may audit or inspect the study site to evaluate the conduct of the 
study. The clinical investigator(s)/institution(s) shall allow study related monitoring, audits, Ethics 
Committee review, and regulatory inspection(s) by providing direct access to source data/documents. If 
study site’s documents are electronic, these must be made available in their original form (or printouts 
signed and dated with the statement that this is complete and true reproduction of the original source 
document) if requested by the sponsor and/or regulatory authority. Study sites should inform Medtronic 
upon notification of an audit by a regulatory body immediately. 
14.4. Confidentiality 
All records and other information about subjects participating in this study will be treated as 
confidential. Data will be transferred and processed by Medtronic or a third party designated by 
Medtronic in a key coded form, unless it is impossible to make it anonymous, for instance, where the 
subject’s name cannot be removed from the data carrier, such as fluoroscopy images. Participating 
subjects will not be identified by name in any published reports about the study. 
14.5. Liability 
Medtronic Japan Co., Ltd. maintains appropriate clinical trial liability insurance coverage as required 
under applicable laws and regulations and will comply with applicable local law and custom concerning 
specific insurance coverage. A documentation explaining compensation to the subjects in the event of 
study-related injuries and if required, a Clinical Trial insurance statement/certificate will be provided to 
the study site for the review of IRB. 
14.6. CIP Amendments 
Approval of 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) 
• 
Geography-specific regulatory authorities (if regulatory approval is required) 
• 
An independent Ethics Committee. 

 
 
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14.7. Required Records and Reports 
 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 (e.g., the study binder provided to the investigator) or Subject Study Binder. 
Electronic 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: 
• 
All correspondence between the Ethics Committee, sponsor, monitor, regulatory authority and 
the investigator that pertains to the investigation, including required reports.  
• 
Subject’s case history records, including:  
o Signed and dated Informed Consent Form.  
o Observations of adverse events/adverse device effects/device deficiencies. 
o Medical history. 
o Implant and follow-up data (if applicable). 
o Documentation of the dates and rationale for any deviation from the CIP. 
• 
Subject identification log. 
• 
List of investigation sites. 
• 
All approved versions of the CIP, IC and other information given to the subject. 
• 
Signed and dated Clinical Trial Agreement.  
• 
Current signed and dated curriculum vitae of Principal Investigator. 
• 
Documentation of delegated tasks.  
• 
Ethics Committee approval documentation. Written information that the investigator or other 
study staff, when member of the Ethics Committee, did not participate in the approval process. 
Approval documentation must include the Ethics Committee composition.   
• 
Regulatory authority notification, correspondence and approval, where required per local law. 
• 
Study training records for site staff.  
• 
Insurance certificates.  
• 
Shipping records of investigational devices. 
• 
Equipment maintenance records, if applicable. 
• 
Any other records that local regulatory agencies require to be maintained.  
• 
Final Study Report including the statistical analysis. 
 

 
 
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The clinical trial data shall be retained for a period until the later of the date of obtaining the 
manufacturing and marketing approval for the medical device pertaining to the 
investigational device (when notification is received pursuant to Article 32, paragraph 3 of 
Ordinance of the Ministry of Health, Labour and Welfare No. 36 of 2005, the date three years 
have passed since the date of notification) or the date three years have passed since the 
discontinuation or termination of the investigational device, whichever is later. 
 Investigator Reports  
The investigator is responsible for the preparation (review and signature) and submission to the 
sponsor of all case report forms, including adverse events and adverse device effects, device 
deficiencies, deaths, and any deviations from the CIP. If any action is taken by an Ethics Committee 
with respect to this clinical study, copies of all pertinent documentation must be forwarded to 
Medtronic in a timely manner. Reports are subject to inspection and to the retention requirements as 
described above for investigator records. 
Safety data investigator reporting requirements are listed in Table 12Table 12 of the Adverse Event 
section 10.5. The investigator shall prepare and submit in a complete, accurate and timely manner the 
reports listed in this section. 
Table 3: Investigator reports applicable per Medtronic requirements 
Report  
Submit to 
Description/Constraints 
Study Deviations  
Sponsor  
Ethics Committee 
Any deviation from the Clinical Investigation Plan shall be reported together with 
the explanation of the deviation as soon as possible upon the site becoming 
aware of the deviation. 
Notice of deviations from the CIP involving 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 
shall be given within 5 working days. Except in such emergency, prior approval is 
required for changes in the plan or deviations. 
 
 

 
 
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Table 4: Investigator reports applicable to Japan 
Report  
Submit to 
Description/Constraints 
Withdrawal of IRB 
approval 
Sponsor and the 
Principal 
Investigator 
The Head of Institution shall notify the principal investigator and the sponsor, 
including promptly issuing written instructions and decision based on the IRB, along 
with a copy of the dated cancellation document of the IRB.  In addition, the Head of 
Institution shall explain in detail and in writing the decision of the IRB to the 
principal investigator and the sponsor.  (MHLW Ordinance 36, Article 51) 
Co-Investigator/ 
Clinical Trial 
Collaborator List 
Head of Medical 
Institution (HOMI) 
When the principal Investigator assigns important parts of the clinical trial duties to 
co-Investigators and/or clinical trial collaborators, he or she shall prepare a list of 
the assigned duties and the individual performing the assigned duties, submit the 
list to the HOMI on the list, and receive the appointments of such individuals. 
(MHLW Ordinance 36, 2005 Article 63) 
Study Deviations 
Sponsor and HOMI 
The Investigator may implement a deviation from, or a change in, the CIP to 
eliminate an immediate hazard(s) to study subjects without prior Ethics Board 
approval. In this case, the Investigator shall immediately submit to the sponsor, the 
HOMI, and to the Ethics Board via the HOMI, the description and reason for the 
deviation and the proposed revision to the CIP, if one is necessary, to receive 
agreement. All deviations, regardless of the reason, shall be submitted to the 
sponsor. (MHLW Ordinance 36, 2005 Article 66) 
Summary of the 
Clinical Study Status HOMI 
 
The investigator shall submit written summaries of the status of the clinical study to 
the Head of Institution annually, or more frequently if requested by the IRB. The 
Head of Institution shall submit to the IRB for the appropriateness of continuing the 
clinical study.  (MHLW Ordinance 36, Article 68) 
 Suspension, 
Termination and 
Completion Report 
HOMI 
When suspending or terminating a clinical study at his or her discretion, the 
principal investigator shall promptly report thereof and submit the details therefor 
in writing to the Head of Institution. 
Upon completion of a clinical study, the principal investigator shall report thereof in 
writing and submit a summary of the results of the clinical study to the Head of 
Institution.  (MHLW Ordinance 36, Article 69) 
Completion of the 
Clinical 
Investigation 
HOMI 
When the clinical study is completed, the principal Investigator shall notify the 
HOMI thereof in writing and report on a summary of the clinical study results in 
writing. (MHLW Ordinance 36, 2005 Article 69) 
 
Additional reporting requirements and if stricter timelines of reporting are required per IRB, the same 
should be complied with, including any reporting needs to regulators, when required by local law. 
 Sponsor Records 
Medtronic shall maintain the following accurate, complete, and current records: 
• 
All correspondence which pertains to the investigation. 
• 
Investigational device traceability records.  
• 
Software traceability records.  

 
 
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• 
Signed Clinical Trial Agreements, and current signed and dated curriculum vitae of Principal 
Investigator (as required by local law), delegated task list. 
• 
All approved Informed Consent templates, and other information provided to the subjects, 
including translations. 
• 
Copies of all Ethics Committee approval letters and relevant Ethics Committee correspondence 
and Ethics Committee voting list/roster/letter of assurance. 
• 
Names of the institutions in which the clinical study will be conducted. 
• 
Regulatory authorities’ correspondence, notification and approval as required by national 
legislation. 
• 
Insurance certificates. 
• 
Names/contact addresses of monitors. 
• 
Site visit reports and follow-up letters. 
• 
Statistical analyses and underlying supporting data. 
• 
Final report of the clinical study. 
• 
The Clinical Investigation Plan, Investigator’s Brochure and study related reports, and 
revisions. 
• 
eCRFs, including AE and Device Deficiency (DD) forms and eCRF corrections. 
• 
Study training records for site personnel and Medtronic personnel involved in the study. 
• 
Any other records that local regulatory agencies require to be maintained. 
 Sponsor Reports 
Medtronic shall prepare and submit the following complete, accurate, and timely reports listed in the 
tables below. In addition to the reports listed below, Medtronic shall, upon request of reviewing Ethics 
Committee or regulatory agency, provide accurate, complete and current information about any aspect 
of the investigation. Safety data Medtronic reporting requirements are listed in Table 12Table 12 of the 
Adverse Event section 10.5. 
 
 

 
 
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Table 5: Sponsor reports for Japan 
Report  
Submit to 
Description/Constraints 
Premature termination or 
suspension of the clinical 
investigation 
HOMI 
PMDA 
When the sponsor suspends or discontinues the clinical trial, he or she 
shall promptly notify therof and the detailed reason(s) thereof in writing 
to the heads of institutions and the regulatory authorities (MHLW 
Ordinance 36, 2005 Article 32) 
Suspension of development of 
investigational device 
HOMI 
PMDA 
When the sponsor decides not to attach the documents concerning 
clinical trial records collected in the clinical trial to the authorization 
application, he or she shall promptly notify the heads of all the medical 
institutions other facilities engaged in the clinical trial thereof and the 
detailed reason therefor in writing. (MHLW Ordinance 36, 2005 Article 32) 
Investigator List 
HOMI 
PMDA 
The sponsor shall beforehand submit the list of Investigators to PMDA and 
HOMI. (Pharmaceutical and Medical Device Act Enforcement Regulations) 
The sponsor shall submit the list of Investigators to PMDA and HOMI 
when making any changes in the list. (Pharmaceutical and Medical Device 
Act Enforcement Regulations) 
 Important information 
concerning the quality, 
efficacy, and safety of the 
investigational device 
Investigators 
HOMI 
PMDA 
and IRB as 
applicable 
Information of affecting subjects’ safety, affecting clinical studies 
performance, or possibility changing the appropriateness of continuing 
clinical study judged by IRB shall be submitted to all Principal Investigators 
and The Head of Institutions.  
The sponsor annually notifies Safety Periodic Report to the Principal 
Investigators and the Heads of Institutions since initial CTN submission to 
the regulatory authority.  
When the sponsor recognizes safety information that is NOT been 
expecting from the Investigator’s brochure (IB), he/she immediately notify 
thereof to the Principal Investigators and the Heads of Institutions.      
The sponsor may directly notify above thereof to the IRBs in addition to 
the Principal Investigators and the Heads of Institutions based on the 
agreement with the IRBs and the Heads of Institutions.   
When new, important information is obtained, the sponsor shall revise 
the IB. In addition, prior to revising the Investigator’s brochure, the 
sponsor shall report the information to the principal investigator, the 
Heads of Institutions, and the regulatory authority. (MHLW Ordinance 36, 
Article 28) 
Clinical Trial Report 
PMDA upon 
request 
The sponsor shall prepare, according to the procedure, a clinical study 
report that summarizes the results, etc., of a clinical study when it is 
completed or discontinued.  The final report should be stored to be 
submitted upon request from the regulatory authority. (MHLW Ordinance 
36, Article 33) 
Study deviation 
Investigators 
HOMI as 
necessary 
When the monitor confirms deviation as a result of monitoring, the 
monitor shall notify the principal investigator and, as necessary, the Head 
of Medical Institution thereof.  The monitor shall also request for 
appropriate measures to be taken to prevent such deviation in the future. 
(MHLW Ordinance 36, 2005 Article 30) 
 

 
 
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Medtronic records and reports will be maintained in a password-protected document management 
system, and paper documents (where applicable) will be stored in secured file cabinets at Medtronic 
during the course of this study. 
After closure of the study, Medtronic will archive records and reports and these will be retained per 
Medtronic standard and applicable regulations. 
14.8. Suspension or Early Termination 
Early Termination is the closure of a clinical study that occurs prior to meeting defined endpoints. This 
is possible for the whole study or a single 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 site. 
 Study-wide Suspension or Early Termination 
Possible reasons for considering study suspension or termination of the study include but are not 
limited to: 
• 
Adverse events associated with the system or product under investigation which might 
endanger the safety or welfare of the subject 
• 
Observed/suspected performance different from the product’s design intent 
• 
Decision by Medtronic or regulatory body (where the study is operating under regulatory 
body authority) 
• 
Technical issues during the manufacturing process 
 Investigator/Site Suspension or Early Termination 
Possible reasons for clinical investigator or site termination or suspension include but are not limited to: 
• 
Failure to obtain initial Ethics Committee approval or annual renewal of the study approval 
• 
Persistent non-compliance to the CIP (e.g., failure to adhere to inclusion/exclusion criteria, 
failure to follow subjects per scheduled follow-ups) 
• 
Lack of enrollment 
• 
Noncompliance to regulations and the terms of the Clinical Trial Agreement (e.g., failure to submit 
data in a timely manner, failure to follow-up on data queries and monitoring findings in a timely 
manner) 
• 
Ethics Committee suspension of the site 

 
 
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• 
Fraud or fraudulent misconduct is discovered (as defined by local law and regulations) 
• 
Investigator request (e.g., no longer able to support the study) 
 Procedures for Suspension or Early Termination 
Below procedures will apply in addition to any other specific requirement per local regulations. 
Medtronic-initiated and regulatory authority-initiated 
• 
Medtronic will promptly inform the clinical investigators of the termination or suspension 
and the reasons and inform the regulatory authority(ies) where required 
• 
In the case of study termination or suspension for reasons other than a temporary EC approval 
lapse, the investigator will promptly inform the EC. A detailed written explanation of the 
termination or suspension will be provided, where required per regulatory requirements. 
• 
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 
 
Investigator-initiated 
• 
The investigator will immediately or promptly 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, along with a detailed written explanation of the 
termination or suspension (where required per regulatory requirements) 
• 
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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Ethics Committee-initiated 
• 
The investigator will inform Medtronic and provide a detailed written explanation of the 
termination or suspension within 5 business days, or sooner if required per local requirements 
• 
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 to ensure appropriate care and 
follow-up is provided 
 
 

 
 
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15. References  
 
1. Weiss R, et al., Safety and efficacy of a totally subcutaneous implantable-cardioverter 
defibrillator, Circulation, 2013;128:944-53 
2. U.S. Food and Drug Administration. (2012). A Patient Guide - Living with your S-ICD 
System. U.S. Food and Drug Administration/Devices@FDA. Retrieved 16-Jan-2018 from: 
http://www.accessdata.fda.gov/cdrh_docs/pdf11/P110042c.pdf. 
3. U.S. Food and Drug Administration. (2012). FDA Circulatory Systems Device Panel 
Transcript for April 26, 2012. U.S. Food and Drug Administration Medical Device 
Advisory Committees. Retrieved 26-Jan-2018 from: 
https://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevi
ces/MedicalDevicesAdvisoryCommittee/CirculatorySystemDevicesPanel/ucm124182.ht
m. 
4. Ellenbogen KA, Wood MA, Shepard RK, Clemo HF, Vaughn T, et al. 2003. Detection and 
management of an implantable cardioverter defibrillator lead failure: incidence and 
clinical implications. J Am Coll Cardiol 41:73-80. 
5. Kleemann T, Becker T, Doenges K, Vater M, Senges J, Schneider S, Saggau W, Weisse U, 
Seidl K.  Annual Rate of Transvenous Defibrillation Lead defect in Implantable 
Cardioverter-Defibrillators over a Period of >10 Years. Circulation. 2007;115:2474-2480. 
6. Bardy GH, et al., An entirely subcutaneous implantable cardioverter-defibrillator, N Engl 
J Med., 2010;363:36-44.  
7. Cappato R, Smith WM, Hood MA, Crozier IG, Jordaens L, Spitzer SG, Ardashev AV, 
Boersma L, Lupo P, Grace AA, Bardy GH. Subcutaneous chronic implantable 
defibrillation systems in humans, J Interv Card Electrophysiol., 2012;34:325–332. 
https://doi.org/10.1007/s10840-012-9665-6. 
8. Tomaske M, Prêtre R, Rahn M, Bauersfeld U. Epicardial and pleural lead ICD systems in 
children and adolescents maintain functionality over 5 years. Europace. 2008 
Oct;10(10):1152-6. 
9. Molina JE, Benditt DG. An epicardial subxiphoid implantable defibrillator lead: superior 
effectiveness after failure of standard implants. Pacing Clin Electrophysiol. 2004 
Nov;27(11):1500-6. 
10. Tung SK, Bennett M, Yeung-Lai-wah JA, Ling H.  Minimal invasive extra cardiac 
placement of high voltage defibrillator leads. Heart Rhythm 2007; 4(5, Suppl.):S200 

 
 
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11. Bauersfeld U, Tomaske M, Dodge-Khatami A, Rahn M, Kellenberger CJ, Prêtre R. Initial 
experience with implantable cardioverter defibrillator systems using epicardial and 
pleural electrodes in pediatric patients. Ann Thorac Surg 2007;84:303-5. 
12. Gold, M., Aasbo, J., El-Chami, M. et al., Subcutaneous implantable cardioverter-
defibrillator Post-Approval Study: Clinical characteristics and perioperative results. 
Heart Rhythm. 2017;14:1456–1463. 
13. Boersma L, Barr C, Knops R et al. Implant and Midterm Outcomes of the Subcutaneous 
Implantable Cardioverter-Defibrillator Registry: The EFFORTLESS Study. J Am Coll 
Cardiol 2017;70:830-841. 
14. Jacob S, Lieberman RA. Percutaneous epicardial defibrillation coil implantation: a viable 
technique to manage refractory defibrillation threshold. Circ Arrhythm Electrophysiol. 
2010 Apr;3(2):214-7. 
15. Haydin S, Saygi M, Ergul Y, Ozyilmaz I, Ozturk E, Akdeniz C, Tuzcu V. Subxiphoid 
approach to epicardial implantation of implantable cardioverter defibrillators in 
children. Pacing Clin Electrophysiol. 2013 Aug;36(8):926-30. 
16. Hajj-Chahine J, Houmaida H, Tomasi J, Corbi P. Epicardial defibrillation patch or coil 
lead? Interact Cardiovasc Thorac Surg. 2011 Apr;12(4):630. 
17. Guenther M, Kolschmann S, Knaut M. Letter to the Editors: Substernal lead 
implantation: A Novel Option to Manage DFT failure in S-ICD Patients. Clin Res Cardiol, 
DOI 10.1007/s00392-014-0764-5. 
18. Boyle TA, Cohen J, Carrillo R. Substernal implantation of a subcutaneous implantable 
cardioverter-defibrillator in a patient with preexisting Hemodialysis Reliable Outflow 
graft. HeartRhythm Case Rep 2016;2:412-414. 
19. Bhagwandien RE, Kik C, Yap SC, Szili-Torok T. Substernal ICD lead implantation in a 
patient not suitable for subcutaneous ICD implantation without venous access due to 
superior vena cava syndrome. HeartRhythm Case Rep 2017;3:97-99. 
20. Hata H, Sumitomo N, Nakai T, Amano A. Retrosternal Implantation of the Cardioverter-
Defibrillator Lead in an Infant. Ann Thorac Surg 2017;103:e449-e451. 
21. Chan JYS, Lelakowski J, Murgatroyd FD, Boersma LV, Cao J, Nikolski V, Wouters G, Hall 
MCS. Novel Extravascular Defibrillation Configuration With a Coil in the Substernal 
Space: The ASD Clinical Study, JACC: Clinical Electrophysiology, Volume 3, Issue 8, 2017, 
Pages 905-910, ISSN 2405-500X, https://doi.org/10.1016/j.jacep.2016.12.026. 
22. Sholevar DP, Tung S, Kuriachan V, et al. Feasibility of extravascular pacing with a novel 
substernal electrode configuration: The Substernal Pacing Acute Clinical Evaluation 

 
 
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Study. Heart Rhythm. Published online 29Nov2017. DOI: 
http://dx.doi.org/10.1016/j.hrthm.2017.11.030 
23. Boersma LV, Merkely B, Neuzil P, Crozier IG, Akula DN, Timmers L, Kalarus Z, Sherfesee 
L, DeGroot PJ, Thompson AE, Lexcen DR, Knight BP. Therapy from a Novel Substernal 
Lead: The ASD2 study. JACC: Clinical Electrophysiology, Volume 5, Issue 2, 2019, Pages 
186-196. 
24. Blatt JA, Poole JE, Johnson GW, et al. No benefit from defibrillation threshold testing in 
the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial). J Am Coll Cardiol. 2008 Aug 
12;52(7):551-6. 
25. Neuzner J, Hohnloser SH, Kutyifa V, et al. Effectiveness of single- vs. dual-coil 
implantable defibrillator leads: An observational analysis from the SIMPLE study. J 
Cardiovasc Electrophysiol. 2019 Apr 4. doi: 10.1111/jce.13943. 
26. Crozier I, Haqqani H, Kotschet E, Shaw D, Prabhu A, Roubos N, et al. First-in-Human 
Chronic Implant Experience of the Substernal Extravascular Implantable Cardioverter 
Defibrillator. J Am Coll Cardiol EP, Nov 2020; 6 (12): 1525-1536. 
27. Crozier I, O'Donnell D, Boersma L, Murgatroyd F, Manlucu J, Knight BP, Birgersdotter-
Green UM, Leclercq C, Thompson A, Sawchuk R, Willey S, Wiggenhorn C, Friedman P. 
The extravascular implantable cardioverter-defibrillator: The pivotal study plan. J 
Cardiovasc Electrophysiol. 2021 Sep;32(9):2371-2378. doi: 10.1111/jce.15190. Epub 
2021 Aug 5. PMID: 34322918. 
28. P. Friedman, F. Murgatroyd, L.V.A. Boersma, J. Manlucu, D. O’Donnell, B.P. Knight, N. 
Clémenty, C. Leclercq, A. Amin, B.P. Merkely, U.M. Birgersdotter‑Green, J.Y.S. Chan, M. Biffi, 
R.E. Knops, G. Engel, I. Muñoz Carvajal, L.M. Epstein, V. Sagi, J.B. Johansen, M. Sterliński, C. 
Steinwender, T. Hounshell, R. Abben, A.E. Thompson, C. Wiggenhorn, S. Willey, and I. Crozier, 
for the Extravascular ICD Pivotal Study Investigators. Efficacy and Safety of an Extravascular 
Implantable Cardioverter–Defibrillator. N Engl J Med 2022; 387:1292-1302 DOI: 
10.1056/NEJMoa2206485. 
 
 

 
 
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16. Appendices  
 
 

 
 
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Appendix A: Draft Data Collection Elements (Case Report Forms) 
Draft Case Report Forms for the EV ICD Japan 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. 
 

 
 
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Appendix B: Instructions for Use 
Instructions for Use (IFU) for the components of the EV ICD System and accessories, and equipment are 
provided with each component under separate cover. The cover of each IFU will have a clinical 
statement on the cover indicating the device is an investigational device. 
 

 
 
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Appendix C: Informed Consent Templates 
Medtronic legal-approved Informed Consent Templates be distributed under separate cover. 
 
 

 
 
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Appendix D: Foreseeable Adverse Event List 
Potential risks associated with the implantation of the EV ICD System, associated harms and adverse 
events, as well as risk minimization are discussed in more detail within section 9, Risks and Benefits. 
The information provided in this section includes additional reference information and may collectively 
assist in identifying those events for a given device or therapy that are unexpected in nature. The 
foreseeable adverse event information consists of three parts: (1) rates of adverse events reported 
from previous Medtronic studies evaluating transvenous ICD systems, (2) adverse event rates reported 
in published literature for procedures similar to EV ICD, and (3) additional adverse events for 
consideration.  An evaluation of potentially anticipated events, adverse device effects observed in 
previous clinical studies, and reported events in literature may be used in combination with device 
labeling, current event reporting information, and other published data to assess for an unexpected 
occurrence.  
The implantation of the EV ICD System involves surgery; therefore, standard adverse events associated 
with a surgical procedure may be experienced (e.g., anesthesia complications, injury, infections, 
bleeding, exacerbation of pre-existing conditions, healing complications). However, the focus of this 
section is to address in more detail, those events that are foreseeable due to the implantation, use, 
performance, and/or presence of the system under investigation or comparable systems. 
Treatment required for procedure and/or system related adverse events may include medication, 
device reprogramming, device modification (e.g., repositioning, electrical abandonment, surgical 
removal), or other surgical and medical remedies.  
Adverse Events Reported in Previous Clinical Studies of Transvenous ICD 
Systems 
Table 6 provides examples of adverse events associated with the use of transvenous ICD systems 
reported in three previous Medtronic studies. These three predicate studies were selected as a 
reference for EV ICD performance as they were contemporary and used adverse event definitions 
consistent with those utilized in the EV ICD Japan Study. The three predicate Medtronic studies include 
BLOCK HF, REVERSE, and Evera MRI. These studies collected adverse event data from 1035 subjects 
that underwent an ICD implant. The average follow-up time exceeded 9 months in all three trials. Table 
6 displays the adverse event rates classified as related to the implanted system and/or procedure. To 
characterize the safety profile of a single lead ICD system, all adverse events related to an atrial or left 
ventricular pacing lead were excluded from consideration. Kaplan-Meier estimates and associated 95% 
confidence intervals of the adverse event rates are provided in the Table below at 30-days and 12-
months (365 days) post-implant to characterize both peri-procedural and long-term adverse events 
related to the procedure or implanted system. 

 
 
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Table 6: System and/or Procedure Related AEs Associated with Transvenous ICD Systems (n=1035) 
 
Within 30-days of Implant 
Within 12-months of Implant 
MedDRA Preferred Term 
No. Events 
(No. Subjects, %) 
95% CI 
No. Events 
(No. Subjects, %) 
95% CI 
ACUTE PULMONARY OEDEMA 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
ADVERSE DRUG REACTION 
5 (5, 0.39%) 
0.15% - 1.03% 
5 (5, 0.39%) 
0.15% - 1.03% 
ANGINA UNSTABLE 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
ANXIETY 
0 (0, 0%) 
-- 
1 (1, 0.13%) 
0.02% - 0.93% 
ARRHYTHMIA SUPRAVENTRICULAR 
1 (1, 0.10%) 
0.01% - 0.68% 
2 (1, 0.10%) 
0.01% - 0.68% 
ATELECTASIS 
3 (3, 0.29%) 
0.09% - 0.90% 
3 (3, 0.29%) 
0.09% - 0.90% 
ATRIAL FIBRILLATION 
8 (7, 0.68%) 
0.32% - 1.41% 
8 (7, 0.68%) 
0.32% - 1.41% 
ATRIAL FLUTTER 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
ATRIAL THROMBOSIS 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.74% 
ATRIOVENTRICULAR BLOCK COMPLETE 
3 (2, 0.19%) 
0.05% - 0.77% 
3 (2, 0.19%) 
0.05% - 0.77% 
ATRIOVENTRICULAR BLOCK THIRD DEGREE 
6 (6, 0.58%) 
0.26% - 1.29% 
6 (6, 0.58%) 
0.26% - 1.29% 
BACTERAEMIA 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.71% 
BODY TEMPERATURE INCREASED 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
BRADYCARDIA 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
BRONCHITIS 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
CARDIAC FAILURE 
16 (16, 1.55%) 
0.95% - 2.52% 
16 (16, 1.55%) 
0.95% - 2.52% 
CARDIAC FAILURE CHRONIC 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
CARDIAC PERFORATION 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
CARDIAC PROCEDURE COMPLICATION 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
CARDIAC TAMPONADE 
2 (2, 0.19%) 
0.05% - 0.77% 
3 (3, 0.29%) 
0.09% - 0.91% 
CEREBROVASCULAR ACCIDENT 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
CHEST PAIN 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
CHRONIC OBSTRUCTIVE PULMONARY DISEASE 
3 (1, 0.10%) 
0.01% - 0.68% 
3 (1, 0.10%) 
0.01% - 0.68% 
COMPLICATION OF DEVICE INSERTION 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
CONTRAST MEDIA REACTION 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
CORONARY SINUS DISSECTION 
9 (9, 0.87%) 
0.45% - 1.66% 
9 (9, 0.87%) 
0.45% - 1.66% 
DECREASED SENSING 
0 (0, 0%) 
-- 
2 (2, 0.28%) 
0.07% - 1.10% 

 
 
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Table 6: System and/or Procedure Related AEs Associated with Transvenous ICD Systems (n=1035) 
 
Within 30-days of Implant 
Within 12-months of Implant 
MedDRA Preferred Term 
No. Events 
(No. Subjects, %) 
95% CI 
No. Events 
(No. Subjects, %) 
95% CI 
DEEP VEIN THROMBOSIS 
2 (2, 0.19%) 
0.05% - 0.77% 
4 (4, 0.40%) 
0.15% - 1.05% 
DEFIBRILLATION THRESHOLD INCREASED 
1 (1, 0.10%) 
0.01% - 0.68% 
2 (2, 0.20%) 
0.05% - 0.79% 
DEHYDRATION 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
DEVICE ELECTRICAL FINDING 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
DEVICE LEAD DAMAGE 
0 (0, 0%) 
-- 
2 (2, 0.23%) 
0.06% - 0.91% 
DEVICE MALFUNCTION 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.74% 
DEVICE MIGRATION 
1 (1, 0.10%) 
0.01% - 0.69% 
2 (2, 0.20%) 
0.05% - 0.78% 
DEVICE RELATED INFECTION 
1 (1, 0.10%) 
0.01% - 0.69% 
1 (1, 0.10%) 
0.01% - 0.69% 
DIZZINESS 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
DRUG HYPERSENSITIVITY 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
DYSPNOEA 
3 (3, 0.29%) 
0.09% - 0.90% 
3 (3, 0.29%) 
0.09% - 0.90% 
DYSPNOEA EXERTIONAL 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
ELECTRICAL RESET OF DEVICE 
0 (0, 0%) 
-- 
2 (2, 0.21%) 
0.05% - 0.82% 
ELECTROMECHANICAL DISSOCIATION 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
ELEVATED PACING THRESHOLD 
0 (0, 0%) 
-- 
2 (2, 0.20%) 
0.05% - 0.81% 
ENTERITIS 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
EXTRASYSTOLES 
1 (1, 0.10%) 
0.01% - 0.69% 
1 (1, 0.10%) 
0.01% - 0.69% 
FAILURE TO CAPTURE 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.73% 
FLUID RETENTION 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
HAEMATOMA 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
HAEMOPNEUMOTHORAX 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
HAEMORRHAGE 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
HYPOTENSION 
8 (8, 0.77%) 
0.39% - 1.54% 
8 (8, 0.77%) 
0.39% - 1.54% 
HYPOXIA 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
IMPAIRED HEALING 
1 (1, 0.10%) 
0.01% - 0.68% 
2 (2, 0.20%) 
0.05% - 0.78% 
IMPLANT SITE CELLULITIS 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.71% 
IMPLANT SITE EROSION 
0 (0, 0%) 
-- 
2 (2, 0.20%) 
0.05% - 0.80% 

 
 
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Table 6: System and/or Procedure Related AEs Associated with Transvenous ICD Systems (n=1035) 
 
Within 30-days of Implant 
Within 12-months of Implant 
MedDRA Preferred Term 
No. Events 
(No. Subjects, %) 
95% CI 
No. Events 
(No. Subjects, %) 
95% CI 
IMPLANT SITE HAEMATOMA 
21 (21, 2.03%) 
1.33% - 3.10% 
23 (23, 2.23%) 
1.49% - 3.34% 
IMPLANT SITE HAEMORRHAGE 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
IMPLANT SITE INFECTION 
8 (8, 0.78%) 
0.39% - 1.54% 
14 (14, 1.38%) 
0.82% - 2.31% 
IMPLANT SITE INFLAMMATION 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.72% 
IMPLANT SITE PAIN 
10 (10, 0.97%) 
0.52% - 1.79% 
19 (18, 1.78%) 
1.13% - 2.81% 
IMPLANT SITE RASH 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
INAPPROPRIATE DEVICE STIMULATION OF TISSUE 
3 (3, 0.29%) 
0.09% - 0.90% 
4 (4, 0.39%) 
0.15% - 1.03% 
INAPPROPRIATE DEVICE THERAPY 
1 (1, 0.10%) 
0.01% - 0.69% 
6 (6, 0.61%) 
0.27% - 1.35% 
INCISION SITE HAEMORRHAGE 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
IODINE ALLERGY 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
JUGULAR VEIN THROMBOSIS 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
KELOID SCAR 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.72% 
LEAD DISLODGEMENT 
14 (14, 1.35%) 
0.80% - 2.27% 
20 (20, 1.96%) 
1.27% - 3.02% 
MEDICAL DEVICE CHANGE 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.74% 
MEDICAL DEVICE COMPLICATION 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.72% 
MEDICAL DEVICE DISCOMFORT 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.72% 
MUSCLE SPASMS 
1 (1, 0.10%) 
0.01% - 0.68% 
2 (2, 0.22%) 
0.05% - 0.89% 
MUSCLE STRAIN 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
MYOCARDIAL INFARCTION 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
OEDEMA PERIPHERAL 
3 (3, 0.29%) 
0.09% - 0.90% 
4 (4, 0.39%) 
0.15% - 1.04% 
ORTHOSTATIC HYPOTENSION 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
OVERSENSING 
1 (1, 0.10%) 
0.01% - 0.68% 
4 (4, 0.41%) 
0.15% - 1.08% 
OXYGEN SATURATION DECREASED 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
PAIN IN EXTREMITY 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
PERICARDIAL EFFUSION 
8 (8, 0.77%) 
0.39% - 1.54% 
9 (9, 0.87%) 
0.45% - 1.67% 
PERICARDITIS 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.71% 
PHANTOM SHOCK 
1 (1, 0.10%) 
0.01% - 0.69% 
1 (1, 0.10%) 
0.01% - 0.69% 

 
 
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Table 6: System and/or Procedure Related AEs Associated with Transvenous ICD Systems (n=1035) 
 
Within 30-days of Implant 
Within 12-months of Implant 
MedDRA Preferred Term 
No. Events 
(No. Subjects, %) 
95% CI 
No. Events 
(No. Subjects, %) 
95% CI 
PLEURAL EFFUSION 
7 (7, 0.68%) 
0.32% - 1.41% 
8 (8, 0.78%) 
0.39% - 1.55% 
PLEURITIC PAIN 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
PNEUMONIA 
3 (3, 0.29%) 
0.09% - 0.90% 
3 (3, 0.29%) 
0.09% - 0.90% 
PNEUMONIA ASPIRATION 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
PNEUMOTHORAX 
4 (4, 0.39%) 
0.15% - 1.03% 
4 (4, 0.39%) 
0.15% - 1.03% 
PNEUMOTHORAX TRAUMATIC 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
PROCEDURAL HYPOTENSION 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
PROCEDURAL NAUSEA 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
PULMONARY EMBOLISM 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.72% 
PULMONARY OEDEMA 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
PUNCTURE OF PERIOSTEUM 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
PYREXIA 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
RENAL FAILURE 
3 (3, 0.29%) 
0.09% - 0.90% 
3 (3, 0.29%) 
0.09% - 0.90% 
RENAL FAILURE ACUTE 
3 (3, 0.29%) 
0.09% - 0.90% 
3 (3, 0.29%) 
0.09% - 0.90% 
SHOULDER PAIN 
4 (4, 0.39%) 
0.15% - 1.03% 
4 (4, 0.39%) 
0.15% - 1.03% 
SLEEP APNOEA SYNDROME 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
SUBCLAVIAN VEIN THROMBOSIS 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
SUPRAVENTRICULAR TACHYCARDIA 
0 (0, 0%) 
-- 
2 (2, 0.21%) 
0.05% - 0.85% 
SUTURE RELATED COMPLICATION 
0 (0, 0%) 
-- 
2 (2, 0.20%) 
0.05% - 0.79% 
SYNCOPE VASOVAGAL 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
THERMAL BURN 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
UNDERSENSING 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
UPPER RESPIRATORY TRACT INFECTION 
1 (1, 0.10%) 
0.01% - 0.69% 
1 (1, 0.10%) 
0.01% - 0.69% 
URINARY RETENTION POSTOPERATIVE 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
VENOUS OCCLUSION 
1 (1, 0.10%) 
0.01% - 0.68% 
2 (2, 0.20%) 
0.05% - 0.79% 
VENTRICULAR ASYSTOLE 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
VENTRICULAR FIBRILLATION 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 

 
 
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Table 6: System and/or Procedure Related AEs Associated with Transvenous ICD Systems (n=1035) 
 
Within 30-days of Implant 
Within 12-months of Implant 
MedDRA Preferred Term 
No. Events 
(No. Subjects, %) 
95% CI 
No. Events 
(No. Subjects, %) 
95% CI 
VENTRICULAR TACHYCARDIA 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
WHEEZING 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
 
Procedure Related Adverse Events from Previous Clinical Studies Using a 
Similar Research System 
Limited clinical experience relevant to the EV ICD System is available from the previously conducted 
Medtronic ASD, SPACE, ASD2, the EV ICD Pilot, and the EV ICD Pivotal studies that utilized similar 
research systems and protocol steps as those in the EV ICD Japan Study.  
In the ASD study, in total ten adverse events were observed. Three adverse events were attributed to 
the ASD Procedure. The first ASD Procedure-related adverse event occurred in the patient where the 
ASD lead was observed implanted in the pleural cavity immediately adjacent to the mediastinum. This 
patient, who underwent a planned indicated surgical procedure requiring midline sternotomy after the 
ASD procedure, had documented decrease in oxygen saturation levels and small bilateral effusions 
reported by the site, diagnosed as chest infection (Note: physician classified this event as not related to 
the ASD Procedure). The small bilateral effusions resolved within five days after onset, and there were 
no further chronic sequelae to the patient.  
The second ASD Procedure-related adverse event was associated with a patient scheduled for CABG 
surgery that had bruising along the left internal mammary artery bed following the ASD tunneling 
procedure, which resulted in a saphenous vein graft being used instead of left internal mammary graft 
in the final (planned) surgical procedure. There were no further sequelae to this patient, and it was 
commented that this may not have been an adverse event, if the graft location had not been changed 
due to the bruising.  
The third ASD Procedure-related adverse event was a patient who had erythema on the back one day 
post-procedure, related to the defibrillation pad of the external defibrillation system (used as a safety 
back-up). The erythema resolved within one day after onset, and there were no further chronic 
sequelae to the patient.  

 
 
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None of the reported adverse events was classified as “related to the ASD Research System” by the 
AEAC.  
In the SPACE study, 14 adverse events were observed, all without chronic sequelae to the patient.  
Two of the adverse events were attributed to the SPACE Procedure. A pericardial effusion was noted in 
one patient (the first patient enrolled in the SPACE study overall) following the patient’s planned 
sternotomy procedure, with the effusion resolved the same day and without extension of the subject’s 
hospital stay beyond standard timeframe; there were no further planned actions deemed necessary 
and no further adverse effects reported for this patient. The second SPACE Procedure-related adverse 
event occurred in a patient whose planned procedure included sternotomy and bypass graft. This 
patient reported incision site pain three days post-procedure that reduced by 16 days and required no 
further follow-up or action. 
In the ASD2 study, there were 20 adverse events (15 serious, 5 non-serious) experienced in 16 subjects.  
Of the 79 subjects who underwent the ASD2 implant procedure, there were seven adverse events in 
seven subjects adjudicated as causally (five) or possibly (two) related to the ASD2 procedure.   
Three of the five adverse events adjudicated as causally related to the ASD2 procedure were classified 
as non-serious and included bleeding at the incision site, erythema and an episode of transient atrial 
fibrillation precipitated during VF induction. The other two adverse events adjudicated as causally 
related to the ASD2 procedure were classified as serious and included one reaction to anesthesia and 
one pericardial effusion with tamponade.  The subject with pericardial effusion was a 62-year-old with 
ischemic cardiomyopathy who developed cardiac tamponade and prolonged hypotension intra-
operatively. Hemodynamic stability was restored through surgical intervention, but the prolonged 
hypotension resulted in hypoxic cerebral injury. With no meaningful neurologic activity after 72 hours, 
supportive care was withdrawn at the family’s request and the subject expired. 
There were two adverse events adjudicated as possibly related to either the ASD2 procedure or the 
subject’s final planned procedure/system: one pericarditis and one cardiac arrest. The subject with 
pericarditis received a dual-chamber ICD implant after the ASD2 procedure, but presented with a 
pericardial effusion on echocardiography three days later. After pericardiocentesis the subject’s 
complaints resolved with no further sequelae. The subject with cardiac arrest was an 81-year-old with 
diabetes and ischemic cardiomyopathy who was admitted for decompensated heart failure, urosepsis 
and persistent AF.  After medical management of these conditions, the subject was enrolled and 
underwent the ASD2 study procedure and planned dual-chamber ICD implantation without incident.  
The subject was then transferred in stable condition to a secondary site where asystole was detected 
36 hours post-procedure.  Despite cardiopulmonary resuscitation for 30 minutes, the subject expired. 

 
 
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The EV ICD Pilot study began enrolling in July 2018 and completed enrollments in December 2018. Thru 
March 11, 2019, data was reported among all 16 subjects with a chronically implanted device that had 
completed their 3-month visit, which was the primary study endpoint.  Among 21 subjects undergoing 
an implant attempt of the system, there were 28 adverse events in 11 subjects.  Six reported adverse 
events in four subjects were adjudicated to be causally related to the implant procedure and/or the EV 
ICD System.  Five of the events (impaired healing, pleuritic pain (2), postoperative wound infection, 
implant site swelling) were causally related to the procedure, while one of the two pleuritic pain 
observations was also related to the EV ICD lead and the other subject with pleuritic pain eventually 
experienced a lead displacement (related to the EV ICD device and lead) leading to an inappropriate 
shock and system removal.  Five of the six events were determined to be non-serious; the lead 
displacement event was classified as a major complication as it involved a system revision. Patient 
follow-up is currently ongoing at the time of this protocol being written. 
The EV ICD Pivotal study began enrolling in 2019 and completed enrollments in 2021; patient follow-up 
is currently ongoing at the time of this protocol being written. Per the PMA Report (v1, 02Aug2022), 
which is currently under regulatory review by the FDA, of the 316 subjects that underwent an implant 
attempt, 23 subjects had a total of 25 major EV ICD System and/or procedure-related complications 
through 182 days post-implant. These include lead dislodgement (10), postoperative wound infection 
(4), device inappropriate shock delivery (2), implant site infection (2), device computer issue (1), device 
placement issue (1), implant site haemorrhage (1), implant site pain (1), incision site impaired healing 
(1), medical device site discomfort (1), and oversensing (1). In addition, at the time of the report, there 
were two additional major system/procedure related complications reported beyond 182 days. Two 
subjects experienced a lead fracture, at 7- and 11-months post-implant. Both subjects initially 
presented with a high voltage impedance out of range alert and had their extravascular ICD system 
explanted. The location of the lead fracture was the same in both subjects, at the proximal end of the 
proximal defibrillation coil. After further investigation, it was determined that both fractures were due 
to excessive lead bending motion, which were not previously observed in pre-clinical or human 
feasibility studies.    
Adverse events in literature 
There are limited published data available regarding the adverse events associated with the 
implantation of a subcutaneous ICD. A summary of adverse events and their published incidence of 2 
studies are listed below:  
1. Weiss R, Knight BP, Gold MR, Leon AR, Herre JM, Hood M, Rashtian M, Kremers M, Crozier I, 
Lee KL, Smith W, Burke MC. Safety and Efficacy of a Totally Subcutaneous Implantable 
Cardioverter Defibrillator. Circulation. 2013 Aug 27;128(9):944-53.  
 

 
 
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This study was a prospective, nonrandomized, multicenter trial of 314 subjects implanted with a 
subcutaneous ICD followed for 180 days. The following adverse events were reported in the 
manuscript.  
Table 7: Safety and Efficacy of a Totally Subcutaneous Implantable Cardioverter Defibrillator, Reported Adverse 
Events  
Adverse Event 
Patients 
Infections 
 
Total Number 
18 
System Explant 
4 
No System Explant 
14 
Inappropriate Shocks 
 
Total Number 
41 
Resulting from normal device function 
16 
Inappropriate Sensing 
25 
Cardiac Oversensing 
22 
Non-Cardiac Oversensing 
3 
Death 
 
Total Number 
8 
Non-cardiac, non-sudden and unrelated to implant 
5 
Unwitnessed death, device interrogation showed 
successful treatment of a singular ventricular 
arrhythmia 
1 
Unwitnessed death, no interrogation available, 
diagnosed with atypical pneumonia and hypoxia 
before death 
1 
Unknown cause of death 
1 
 
2. Maass AH, de Groot JR, van Oostrom AJ, Theuns DA, Jordaens LJ, Wilde AA, Knops RE. The 
entirely subcutaneous implantable cardioverter-defibrillator: initial clinical experience in a 
large Dutch cohort. J Am Coll Cardiol. 2012 Nov 6;60(19):1933-9.  
 
This was a retrospective study using the files of 118 consecutive patients implanted with a 
subcutaneous ICD system. Patient experience through 18 months post-implant was included in the 
dataset. Adverse events observed included the following:  
Table 8: The entirely subcutaneous implantable cardioverter-defibrillator: initial clinical experience in a large 
Dutch cohort, Reported Adverse Events 
Adverse Event 
Patients 
Episodes 
Inappropriate Shocks 
 
 

 
 
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Adverse Event 
Patients 
Episodes 
Total Number 
15 
33 
T-wave oversensing 
9 
11 
Myopotentials 
3 
4 
Double Counting 
1 
15 
Atrial Flutter 
1 
2 
TENS Therapy 
1 
1 
Complications 
 
 
Total Number 
16 
 
Lead Dislodgement 
3 
 
Device Dislodgement 
1 
 
Infection 
7 
 
Premature Battery Depletion 
2 
 
Skin Erosion 
2 
 
Explant because of need for ATP 
1 
 
 
Additional Adverse Events 
The above incidences of each adverse event were reported from the collection of similar Medtronic 
studies. Events that have been experienced in other Medtronic studies that have the potential to be 
experienced by subjects, or may have been reported with different terminology also include: 
Anemia, Aneurysm or pseudo-aneurysm, Angina pectoris, Aphasia, Arterio-venous fistula, Asystole, 
Atrial septal defect, Back pain, Blood or air embolism, Bruising, Cardiac dissection, Cardiogenic shock, 
Cellulitis, Constrictive pericarditis, Coronary artery constriction, Coronary artery disease, Coronary 
artery occlusion, Coronary vein occlusion, Device capture issue, Device connection issue, Device lead 
issue, Device pacing issue, Device protrusion, Device signal detection issue, Diaphoresis, Dressler's 
syndrome, Dysplasia, Ecchymosis, Edema, Electrical conduction disorders, Electrical shock, 
Electromagnetic interference, Endocarditis, Erythema, Exit block, Extravasation, Failure to terminate a 
ventricular tachycardia/ ventricular fibrillation, Fatigue, Fever, Headache, Heart block, Heart rate 
increase, Hematuria, Hyperkalemia, Hypertension, Impedance decreased, Impedance increased, 
Implant site abscess, Implant site complication, Implant site discomfort, Implant site drainage, Implant 
site seroma, Implant site swelling, Inappropriate device detection, Inappropriate device programming, 
Inflammation, Insomnia, Lead insertion tool delivery problem, Local swelling, Loss of consciousness, 
Mental status change, Musculoskeletal discomfort, Myocardial damage, Myocardial irritability, Neck 
pain, Necrosis, Neurological symptoms, Numbness at incision site, Numbness in hand, Panic attack, 
Paresthesia, Pericardial rub, Phlebitis, Poor hemodynamic recovery, Presyncope, Reduced cardiac 
output, Reduced perfusion, Respiratory failure, Restlessness, Retrosternal pain, Scar or scarring, Sepsis, 
Septic shock, Skin injuries, Skin reaction, Sleep apnea, Stroke, Subcutaneous emphysema, Sudden 

 
 
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cardiac death, Thoracic pain, Thrombocytopenia, Thromboembolism, Thrombosis, Nerve damage, 
Transient ischemic attack, Urticaria, Valve damage, Vascular trauma, Vasovagal reaction, Venous 
insufficiency, Venous stenosis, Ventricular extrasystole, Vessel perforation or laceration, Vessel spasm, 
Vomiting, Weakness. 
 
 

 
 
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Appendix E: Participating Investigators and Institutions 
A complete list of participating investigators and institutions will be provided under separate cover. 
 
 

 
 
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Appendix F: Ethics Committee and Competent Authority List 
A complete list of participating Regulatory Bodies, Competent Authorities, and Ethics Committees and 
their Chairperson(s) that will be utilized as part of the study will be distributed under separate cover, 
upon request.  

 
 
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Appendix G: Previous Clinical Investigations 
A complete bibliography and summary of relevant literature, summary and results of preclinical testing, 
and summary of results of previous clinical investigations is provided in the Investigator’s Brochure. 
 
 

 
 
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Appendix H: Chronic Defibrillation Testing Protocol 
If a chronic defibrillation test is performed per physician discretion, the following chronic defibrillation 
protocol is recommended. When the chronic defibrillation test protocol has been followed, it’s 
considered to have passed chronic defibrillation testing criteria. Specifically, each subject will be 
induced to produce up to two episodes of SSVA and allowed two shock attempts to convert each SSVA 
from the EV ICD, for up to a total of 4 potential shocks from the EV ICD (see Figure 9). Starting therapy 
polarity is at the discretion of the physician (in the programmed setting). 
 
Figure 9: Diagram outlining the process of chronic SSVA induction and defibrillation testing  
 
Episode 1 
Program Rx1 and Rx2 therapies as follows: 
  
Rx1 
Rx2 
NID 
30/40 
NA 
Redetect NID 
NA 
9/12 
VF Therapy Status 
ON 
ON 
Energy 
30J 
40J 
Pathway 
As 
programmed 
As 
programmed 

 
 
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If Episode 1, Rx1 or Rx2 is successful in terminating the episode, the EV ICD System will have passed 
chronic defibrillation testing criteria. No additional inductions are required, and it is recommended to 
leave the system implanted with no changes. 
Episode 2 
  
Rx1 
Rx2 
NID 
9/12 
NA 
Redetect NID 
NA 
9/12 
VF Therapy Status 
ON 
ON 
Energy 
40J 
40J 
Pathway 
Opposite of 
programmed 
Opposite of 
programmed 
If Episode 2, Rx1 or Rx2 is successful in terminating the episode, the EV ICD System will have passed 
chronic defibrillation testing criteria. No additional inductions are required, and it is recommended to 
leave the system implanted with no changes. 
If both Rx1 and Rx2 fail in Episode 2, the EV ICD System will have failed chronic defibrillation testing 
criteria and the next steps are at the physician’s discretion. Medtronic recommends EV ICD device or 
lead revision (at a minimum), or system removal.  
Prior to inducing and throughout the chronic defibrillation protocol, it is recommended to consider the 
following to improve defibrillation outcome or troubleshooting in the event of failure of first 
episode(s):  
• 
Check for/resolve high impedance values 
• 
Check for/resolve air in tunnel (e.g., fluoroscopy) 
• 
Check for/resolve gastric bubbles (gas) 
• 
Press on device pocket during testing 
• 
Perform defibrillation during held end tidal expiration (end expiration apnea) 
 
 

 
 
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Appendix I: Investigator Statement 
Study product Name 
Extravascular ICD System 
Sponsor 
Medtronic Japan Co., Ltd. 
1-2-70 Konan, Minato-ku, 
Tokyo Japan 108-0075 
Shinagawa Season Terrace 22F 
Phone: (+81) 3-6774-4611 
Fax: (+81) 3-6774-4605 
 
Clinical Investigation Plan Identifier 
MDT22010 
Version Number/Date  
3.0, 21-OCT-2022 
I have read the protocol, including all appendices, and I agree that it contains all necessary details for 
me and my staff to conduct this study as described. I will conduct this study as outlined herein and 
will make a reasonable effort to complete the study within the time designated. 
I agree to comply with the Declaration of Helsinki, the Clinical Investigation Plan, and Good Clinical 
Practice, as well as local laws, regulations, and standards. I agree to ensure that the confidential 
information contained in this document will not be used for any purpose other than the evaluation 
and conduct of the clinical investigation without the prior written consent of Medtronic. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Medtronic. I will discuss this material with them to ensure that they are 
fully informed about the products and the study. 
Investigator’s Signature: 
 
Investigator’s Name: 
 
Institution: 
 
Date:  
 
17. Version History 
 
Version 
Summary of Changes 
Author(s)/Title 
1.0 
Initial version for EV ICD Japan Study. 
Takuto Yamamoto 
Clinical Research Specialist 
2.0 
• 
Added “safety” to the purpose of this 
study overall. 
Takuto Yamamoto 
Clinical Research Specialist 

 
 
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• 
Added "Chronic Defibrillation Testing" to 
“Study Procedures and Assessments” of 
Section 2 "Synopsis". 
• 
Added that a copy of the consent 
document should be given to the subject 
to Section 8.3 "Subject Consent". 
• 
Updated section 8.5.5 “Implant 
Procedure Steps” based on experience in 
EV ICD Pivotal Study. 
• 
Corrected the article number in “study 
deviation” of 14.7.4 “Sponsor Reports”.  
• 
Deleted Appendix “Applicability to CMS 
Beneficiaries”. 
• 
Updated CIP version number/date in 
Appendix “Investigator Statement”. 
3.0 
• 
Deleted “UADE” and UADE related 
descriptions overall. 
• 
Updated section 3.1 “Background” to add 
status of the EV ICD Pivotal Study. 
• 
Updated section 5.1 “Duration”. 
• 
Updated section 8.11 “CareLink 
Transmissions” to have a consistency 
with the current situation. 
• 
Updated ISO14155 definition in section 
10.3 “Adverse Events and Device 
Deficiency Definitions” from 2011 to 
2020. 
• 
Updated Appendix D to update the status 
of EV ICD Pilot and Pivotal Study. 
Takuto Yamamoto 
Sr Clinical Research Specialist