Reveal LINQ™ Heart Failure
Conditions: Heart Failure
Sponsor: Medtronic Cardiac Rhythm and Heart Failure

056-F154, Clinical Study Document Approval Form, Version 4.0
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 Medtronic: 
Clinical Study Document Approval Form 
Study Name/Identifier Reveal UNQ Heart Failure (HF) 
Document Name Clinical Investigation Plan Version 2.0 
Document Reference Number N/A 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
) 
This document is electronically controlled. Printed copies are considered uncontrolled. 
Confidential 

056-F154, Clinical Study Document Approval Form, Version 4.0
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This document is electronically controlled. Printed copies are considered uncontrolled. 
Confidential 

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 Reveal LINQ™ Heart 
Failure (HF) 
Clinical Investigation Plan 
Version 2.0 
26 Oct 2016 
Regional Sponsors and Contacts 
United States (Sponsor) 
Medtronic, Inc. 
8200 Coral Sea Street NE 
Mounds View, MN U.S.A. 55112 
1-800-328-2518

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TABLE OF CONTENTS 
1 
ADMINISTRATIVE INFORMATION .............................................................................. 8 
1.1 
List of Abbreviations ....................................................................................................................... 8 
1.2 
Sponsor Contact Information .......................................................................................................... 8 
1.3 
CROs and Core Labs ........................................................................................................................ 9 
1.4 
Steering Committee ........................................................................................................................ 9 
2 
SYNOPSIS .......................................................................................................................... 10 
3 
INTRODUCTION ............................................................................................................. 14 
3.1 
Study Purpose ............................................................................................................................... 14 
3.2 
Study Description.......................................................................................................................... 14 
4 
BACKGROUND AND JUSTIFICATION ....................................................................... 15 
5 
SYSTEM DESCRIPTION AND INTENDED USE ........................................................ 16 
5.1 
Reveal LINQ™ Insertable Cardiac Monitor (ICM) ........................................................................... 17 
5.2 
Incision Tool.................................................................................................................................. 17 
5.3 
Insertion Tool ............................................................................................................................... 17 
5.4 
2090 Programmer ......................................................................................................................... 18 
5.5 
Medtronic LINQ™ HF Investigational RAMware ............................................................................ 18 
5.6 
Patient Assistant ........................................................................................................................... 19 
5.7 
MyCareLink® Home Monitor ......................................................................................................... 19 
5.8 
DR 220 Holter Monitor .................................................................................................................. 20 
6 
REGULATORY COMPLIANCE ...................................................................................... 21 
6.1 
Governing Regulations .................................................................................................................. 21 
6.2 
Institutional Review Board ........................................................................................................... 21 

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6.3 
CIP/CIP Amendments .................................................................................................................... 21 
6.4 
Subject Materials .......................................................................................................................... 21 
7 
METHODOLOGY ............................................................................................................. 22 
7.1 
Study Design ................................................................................................................................. 22 
7.2 
Objective ...................................................................................................................................... 22 
7.2.1 
Primary objective ...................................................................................................................... 22 
7.3 
Subject Selection Criteria .............................................................................................................. 22 
7.3.1 
Inclusion criteria ........................................................................................................................ 22 
7.3.2 
Exclusion criteria ....................................................................................................................... 23 
7.4 
Minimization of Bias ..................................................................................................................... 23 
8 
STUDY PROCEDURES ................................................................................................... 24 
8.1 
Investigator and Site Selection Criteria ......................................................................................... 24 
8.2 
Site Activation .............................................................................................................................. 24 
8.3 
Equipment Requirements ............................................................................................................. 25 
8.4 
Data Collection ............................................................................................................................. 25 
8.5 
Role of the Sponsor Representatives ............................................................................................ 26 
8.6 
Patient Informed Consent Process ................................................................................................ 27 
8.7 
Enrollment .................................................................................................................................... 28 
8.8 
Baseline ........................................................................................................................................ 28 
8.9 
Insertion ....................................................................................................................................... 29 
8.9.1 
Programming Recommendations .............................................................................................. 30 
8.10 Scheduled Follow-up visits ............................................................................................................ 30 
8.11 Device Transmission/ HCU Monthly Call (Start within Month 1) ................................................... 31 
8.12 Monthly CareLink Transmissions .................................................................................................. 31 
8.13 Device Interrogation ..................................................................................................................... 32 
8.14 Healthcare Utilization ................................................................................................................... 32 
8.15 System Modification ..................................................................................................................... 32 

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8.16 Study Exit ...................................................................................................................................... 33 
8.17 Medications .................................................................................................................................. 34 
8.18 6 Minute Hall Walk Test ................................................................................................................ 34 
 
 
8.21 Review of Data Recorded by the Reveal LINQ™ Device ................................................................. 34 
8.22 Holter ........................................................................................................................................... 34 
9 
INVESTIGATIONAL DEVICE/RAMWARE STORAGE, HANDLING AND 
TRACEABILITY ........................................................................................................................ 36 
9.1 
Medtronic Supplied Equipment Accountability ............................................................................. 36 
9.1.1 
Shipment of Study Components ................................................................................................ 37 
9.1.2 
Storage and Handling of Study Device and Components .......................................................... 37 
10 
STUDY DEVIATIONS ................................................................................................. 38 
11 
ADVERSE EVENTS AND DEVICE DEFICIENCIES ............................................... 39 
11.1 Adverse Event and Device Deficiency Definitions ......................................................................... 39 
11.2 Adverse Event and Device Deficiency Assessment ........................................................................ 41 
11.2.1 
Adverse Events ..................................................................................................................... 41 
11.2.2 
Device Deficiencies ............................................................................................................... 41 
11.2.3 
Processing Updates and Resolution ..................................................................................... 41 
11.3 Adverse Events and Device Deficiency Classification..................................................................... 42 
11.4 Adverse Event and Device Deficiency Reporting Requirements .................................................... 43 
11.5 Subject Death ............................................................................................................................... 43 
11.5.1 
Death Data Collection ........................................................................................................... 43 
11.5.2 
Death Classification and Reporting ....................................................................................... 44 
11.6 Clinical Events Committee (CEC) review ........................................................................................ 45 
11.7 Product Complaint Reporting........................................................................................................ 45 
12 
RISK ANALYSIS ........................................................................................................... 47 
12.1 Risk Minimization ......................................................................................................................... 48 

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12.2 Potential Benefits ......................................................................................................................... 49 
12.3 Risk-to-Benefit Analysis ................................................................................................................ 50 
13 
PLANNED STUDY CLOSURE, EARLY TERMINATIONOF STUDY OR STUDY 
SUSPENSION ............................................................................................................................. 51 
13.1 Planned Study Closure .................................................................................................................. 51 
13.2 Early Termination or Suspension .................................................................................................. 51 
13.2.1 
Study-wide Termination or Suspension ................................................................................ 51 
13.2.2 
Investigator/center Termination or Suspension ................................................................... 51 
13.3 Procedures for Termination or Suspension ................................................................................... 52 
13.3.1 
Medtronic-initiated and Regulatory Authority-initiated ...................................................... 52 
13.3.2 
Investigator-initiated ............................................................................................................ 52 
13.3.3 
IRB-initiated .......................................................................................................................... 52 
14 
STATISTICAL METHODS AND DATA ANALYSIS .............................................. 53 
14.1 General Considerations ................................................................................................................. 53 
14.2 Primary Objective ......................................................................................................................... 53 
14.2.1 
Endpoint Definitions ............................................................................................................. 53 
14.2.2 
Analysis Methods .................................................................................................................. 53 
14.2.3 
Determination of Patients/Data for Analysis ........................................................................ 53 
14.2.4 
Sample Size ........................................................................................................................... 53 
14.2.5 
Heart Failure (HF) Event Definition ....................................................................................... 54 
14.3 Interim Analysis ............................................................................................................................ 54 
14.4 Missing Data ................................................................................................................................. 54 
14.5 Subgroup Analysis......................................................................................................................... 54 
15 
DATA AND QUALITY MANAGEMENT .................................................................. 55 
16 
WARRANTY/INSURANCE INFORMATION ......................................................... 56 
16.1 Warranty ...................................................................................................................................... 56 
17 
MONITORING .............................................................................................................. 57 
17.1 Monitoring Visits .......................................................................................................................... 57 
17.2 Access to the Site and Study Materials ......................................................................................... 57 

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18 
REQUIRED RECORDS AND REPORTS .................................................................. 58 
18.1 Investigator Records ..................................................................................................................... 58 
18.2 Investigator Reports ..................................................................................................................... 59 
18.3 Sponsor Records ........................................................................................................................... 60 
18.4 Sponsor Reports ........................................................................................................................... 60 
 
Listing of Tables 
Table 1: Study Sponsor Contact Information ................................................................... 8 
Table 2: CRO and Core Lab Information ......................................................................... 9 
Table 3: Steering Committee Contact Information ........................................................... 9 
Table 4: System Component Information ...................................................................... 11 
Table 5: Data Collection and Study Procedure Requirements at Subject Visits ............. 13 
Table 6: System Component Information ...................................................................... 16 
Table 7: Data Collection and Study Procedure Requirements at Subject Visits ............. 26 
Table 8: Post-Insertion Follow-up Windows ................................................................... 30 
Table 9: Final Disposition of Products ........................................................................... 37 
Table 10: Adverse Event Definitions .............................................................................. 39 
Table 11: Adverse Event Classification Responsibilities ................................................ 42 
Table 12: Adverse Event Reporting Requirements ........................................................ 43 
Table 13: Subject Death Classification Responsibilities ................................................. 45 
Table 14: Potential Risks and Risk Minimization ........................................................... 48 
Table 15: Investigator Reports per Medtronic Requirements ......................................... 59 
Table 16: Sponsor Reports............................................................................................ 61 
 
Listing of Figures 
Figure 1: Reveal LINQ™ ICM ........................................................................................ 17 
Figure 2: Incision Tool ................................................................................................... 17 
Figure 3: Insertion Tool ................................................................................................. 18 
Figure 4: Medtronic 2090 Programmer .......................................................................... 18 
Figure 5: Patient Assistant............................................................................................. 19 
Figure 6: MyCareLink® Home Monitor .......................................................................... 19 
Figure 7: DR220 Holter ................................................................................................. 20 
Figure 8: Recommended Insertion Locations ................................................................ 29 
 
Listing of Appendices 
Appendix A: Data Collection Elements (Case Report Forms) ........................................ 62 
Appendix B: Preliminary Publication Plan ...................................................................... 63 
Appendix C: LINQ™ HF Study Procedure Handbook .................................................... 65 
Appendix D: Patient Informed Consent Form Template ................................................. 66 
Appendix E: Participating Investigators and Institutions ................................................. 67 
Appendix F: IRB Committee List ................................................................................... 68 

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Appendix G: Labeling .................................................................................................... 69 
Appendix H: Bibliography .............................................................................................. 70 
Appendix I: Pre-clinical Testing ..................................................................................... 72 
Appendix J: Previous Clinical Investigations .................................................................. 73 
Appendix K: Committees ............................................................................................... 74 
Appendix L: Summary of Changes ................................................................................ 75 
 
 

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1 ADMINISTRATIVE INFORMATION 
 
1.1 List of Abbreviations 
AE: Adverse Event 
ADHF: Acute decompensated heart failure 
AF: Atrial Fibrillation 
AHF: Acute Heart Failure 
CEC: Clinical Events Committee 
CIP: Clinical Investigational Plan 
CRF: Case Report Form 
CRT: Cardiac Resynchronization Therapy 
CTA: Clinical Trial Agreement 
eCRF: electronic Case Report Form 
ECG: Electrocardiogram 
EF: Ejection Fraction 
FDA: Food and Drug Administration 
GCP: Good Clinical Practice 
HCU: Healthcare Utilization 
HF: Heart Failure 
ICD: Implantable Cardioverter-Defibrillator  
ICM: Insertable Cardiac Monitor 
IPG: Implantable Pulse Generator 
IRB: Institutional Review Board 
MDT: Medtronic 
PIC: Patient Informed Consent 
RAMware: Software downloaded onto LINQ™ device 
RDC: Remote data capture 
RPIS: Report of Prior Investigations 
SAE: Serious Adverse Event 
SCD: Sudden Cardiac Death 
 
1.2 Sponsor Contact Information 
Medtronic contact information is provided below. This information is subject to change 
during the course of the clinical study. Periodic updates to study contact information will 
be sent to the centers as needed. A complete listing of the monitors will be maintained in 
a separate cover. 
Table 1: Study Sponsor Contact Information 
Study sponsors and contacts  
Worldwide clinical study leader 
 
Kara Southall, Pr. Clinical Research Specialist 
8200 Coral Sea Street NE 
Mounds View, MN U.S.A. 55112 
Phone: 612-963-2640 
Email: kara.l.southall@medtronic.com 
Worldwide monitoring leader 
 
Taryn Randall, Clinical Monitoring Manager 
8200 Coral Sea Street NE 
Mounds View, MN U.S.A. 55112 
Phone: 763-250-0785 
Email: taryn.randall@medtronic.com  

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1.3 CROs and Core Labs 
CRO and core lab information is provided below. This information is subject to change 
during the course of the clinical study. Periodic updates to CRO and core labs 
information will be sent to the centers as needed. 
Table 2: CRO and Core Lab Information 
Contact Information 
Duties performed 
Cognizant Technology Solutions 
500 Frank W. Burr Blvd. 
Teaneck, NJ 07666 
Direct Phone: (201) 801-0233 
Direct Fax: (201) 801-0243 
•
Development of study electronic case report forms, edit 
checks, and study management reports.
•
Review of electronic case report forms, management
of discrepancies, and coding of medications and
deviations.
1.4 Steering Committee 
Steering Committee contact information is provided below. 
Table 3: Steering Committee Contact Information 
Name 
Contact Information 
Sanjeev Gulati, MD 
Sanger Heart & Vascular Institute/ Carolinas 
HealthCare System 
Charlotte, NC 
 
Michael Zile, MD 
Medical University of South Carolina 
Charleston, SC 
 
Mandeep Mehra, MD 
Brigham and Women’s Hospital 
Boston, MA 
 
Gregg Fonarow, MD 
University of California Los Angeles 
Los Angeles, CA 
 

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2 SYNOPSIS 
       TITLE 
Reveal LINQ™ Heart Failure (HF) Clinical Study 
PURPOSE 
The LINQ™ HF study is a Non-Significant Risk Investigational Device Exemption (IDE) 
study. The study is utilizing the Reveal LINQ™ device with an investigational LINQ™ HF 
RAMware download.
 
 
   
The purpose of the LINQ™ HF study is to characterize Reveal LINQ™ derived data from 
patients with heart failure by assessing the relationship between changes in LINQ™ 
derived data and other physiologic parameters with subsequent acute decompensated 
heart failure (ADHF) events. The study will also collect information regarding HF related 
clinical events during the same period. 
DESIGN 
The study is a prospective, non-randomized, multi-center, observational, pre-market 
clinical study.  The study is expected to be conducted at up to 30 centers in the United 
States. Up to 300 subjects will be enrolled to achieve approximately 40 heart failure 
events (no more than two per subject will contribute to the cumulative total). Study 
subjects will be followed for up to 3 years post-insertion or until official study closure 
defined as when Medtronic and/or regulatory requirements have been satisfied per the 
Clinical Investigation Plan and/or by a decision by Medtronic or regulatory authority, 
whichever occurs first. The expected study duration is approximately 4 years 
representing 1.5 years of enrollments and 2.5 years of follow-up. 

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MEDICAL DEVICE 
Table 4: System Component Information 
Model 
Number 
Component 
Manufacturer 
Investigational or 
Market-released 
LNQ11 
Reveal LINQ™ Insertable Cardiac 
Monitor 
Medtronic 
Market-Released* 
LNQ11 
Incision Tool 
Medtronic 
Market-Released 
LNQ11 
Insertion Tool 
Medtronic 
Market-Released 
SW026 
2090 Programmer 
Medtronic 
Market-Released* 
Not 
Applicable 
Reveal LINQ™ RAMware titled: LINQ 
HF Research System, Rev 1.0, and 
subsequent versions as they are 
released** 
Medtronic 
Investigational 
PA96000 
Patient Assistant 
Medtronic 
Market-Released 
24950 
MyCareLink® Home Monitor 
Medtronic 
Market-Released 
DR220 
Holter 
NorthEast 
Monitoring, Inc. 
Market-Released 
*The LINQ™ device and the 2090 programmer are market-released, but once the investigational LINQ™ HF
RAMware is downloaded into the devices, they are considered investigational.
**Subjects will receive the most current approved version of the investigational RAMware at the time of their 
device insertion. In the case that a new RAMware version is released during the course of the study, 
subjects previously receiving an older version of the RAMware will receive an upgrade to the new version.  
OBJECTIVE 
Primary Objective: The primary objective is to characterize Reveal LINQ™ derived data 
from patients with heart failure by assessing the relationship between changes in 
LINQ™ derived data and other physiologic parameters with subsequent ADHF events. 
SUBJECT POPULATION 
The subject population for the LINQ™ HF study is patients with heart failure with a 
NYHA Class III. Inclusion and Exclusion criteria are listed below. 
INCLUSION CRITERIA 
•
Patient is 18 years of age or older
•
Patient (or patient’s legally authorized representative) is willing and able to provide
written informed consent
•
Patient is willing and able to comply with the protocol, including follow-up visits and
Carelink transmissions
•
Patient is NYHA Class III, per most recent assessment or at any time within 30 days
prior to enrollment
•
Patient had a HF event (HF event defined as meeting any one of the following three
criteria):
1. Admission with primary diagnosis of HF within the last 6 months, OR
2. Intravenous HF therapy (e.g. IV diuretics/vasodilators) or ultrafiltration at any
one of the following settings within the last 6 months:

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Admission with secondary/tertiary diagnosis of HF
-
Emergency Department
-
Ambulance
-
Observation Unit
-
Urgent Care
-
HF/Cardiology Clinic
-
Patient’s Home, OR
3. Patient had the following BNP/NTpro-BNP within the last 3 months:
-
If EF ≥ 50%, then BNP> 200 pg/ml or NTpro-BNP > 400 pg/ml OR
-
If EF is <50%, then BNP> 400 pg/ml or NTpro-BNP > 800 pg/ml
EXCLUSION CRITERIA 
•
Patient is pregnant (all females of child-bearing potential must have a negative
pregnancy test within 1 week of enrollment)
•
Patient is enrolled in another study that could confound the results of this study,
without documented pre-approval from a Medtronic study manager
•
Patient has severe valvular heart disease as defined by hemodynamically significant
valve stenosis and/or prosthetic heart valve
•
Patient has existing IPG, ICD, CRT-D or CRT-P device
•
Patient has severe renal impairment (eGFR <25mL/min)
CLINICAL PROCEDURES 
A patient will be considered enrolled in the study once they sign and date the patient 
informed consent (PIC). The subjects will be followed via 1, 6 and 12 month in-office 
visits as well as monthly device transmission/healthcare utilization (HCU) calls. Study 
subjects will be followed for up to 3 years post-insertion or until official study closure 
defined as when Medtronic and/or regulatory requirements have been satisfied per the 
Clinical Investigation Plan and/or by a decision by Medtronic or regulatory authority, 
whichever occurs first. Table 4 below describes the required data collection and study 
procedures at the subject’s visits. 

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Table 5: Data Collection and Study Procedure Requirements at Subject Visits 
*DR220 Holter is recommended at the 6 Month Visits.
STUDY PROCEDURE 
Baseline 
LINQ Insertion 
1 Mo Visit 
6 Mo and 12 
Mo Office 
Visit 
Device 
Transmission/  
HCU Monthly 
Call 
Study Exit 
Patient Informed Consent 
X 
Inclusion/Exclusion Assessment 
X 
Medical History 
X 
Demographics 
X 
Physical Exam 
X 
X 
X 
Medication Assessment 
X 
X 
X 
X 
Laboratory results 
X 
X 
Symptoms and Temperature (via ear is recommended) 
X 
X 
Final system configuration 
X 
Insertion procedure information 
X 
LINQ™ HF RAMware download onto LINQ™ device 
X 
 
X 
Device Data 
X 
X 
X 
X 
X 
NYHA functional classification assessment 
X 
X 
6 minute hall walk test 
X 
X 
Holter (DR220) with 6 Minute Hall Walk Test (Recommended) 
X* 
 
X 
X 
LINQ™ HF RAMware removal from LINQ™ device 
X 
Adverse Event 
As Occurs 
Healthcare Utilization 
Device Deficiency 
System Modification 
Study Deviations 
Death 

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3 INTRODUCTION 
3.1 Study Purpose 
Medtronic, Inc. is sponsoring the Reveal LINQ™ Heart Failure (HF) study, a prospective, 
non-randomized, multi-center, observational, pre-market clinical study. The purpose of 
this clinical study is to characterize Reveal LINQ™ derived data from patients with heart 
failure by assessing the relationship between changes in LINQ™ derived data and other 
physiologic parameters with subsequent acute decompensated heart failure events 
(ADHF).  
The study is utilizing the Reveal LINQ™ device with an investigational LINQ™ HF 
RAMware. 
 
 
 
 Additionally, the device will collect the standard information 
collected in the market released LINQ™ device such as atrial fibrillation burden, average 
ventricular rate during AF, night and day heart rate and heart rate variability.  The study 
will also collect information regarding HF related clinical events during the same period. 
3.2 Study Description 
The study is expected to be conducted at up to 30 centers located in the United States. 
Up to 300 subjects will be enrolled to achieve approximately 40 heart failure events (no 
more than two per subject will contribute to the cumulative total). Approximately 300 
LINQ™ devices will be used in the study.  
To ensure a widespread distribution of data and minimize center bias in study results, 
the maximum number of subjects enrolled at a single center is 60 subjects. 
Study subjects will be followed for up to 3 years post-insertion or until official study 
closure defined as when Medtronic and/or regulatory requirements have been satisfied 
per the Clinical Investigation Plan and/or by a decision by Medtronic or regulatory 
authority, whichever occurs first.  Accordingly, the expected total study duration is 
approximately 4 years, representing approximately 1.5 years of patient enrollment and 
2.5 years of subject follow-up. 
. 

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4 BACKGROUND AND JUSTIFICATION 
Acute decompensated heart failure (ADHF) is the leading cause of hospitalizations in 
patients aged 65 and older. In 2004, ADHF accounted for over one million 
hospitalizations and >6.5 million inpatient days. Heart Failure (HF) is the most common 
diagnosis associated with 30-day readmission to hospitals in the US. Twenty percent of 
Medicare beneficiaries are re-hospitalized within 30 days of HF discharge, and 37% of 
those repeat hospitalizations are again due to HF. It is estimated that about 90% of 
these hospitalizations are unplanned and potentially preventable. Recurrent 
hospitalizations account for over 75% of the $46 billion in annual US HF expenditures.1 
Reducing healthcare utilization associated with HF patient management (i.e. short-term 
readmission and chronic disease management) is a critically important unmet need for 
patients, caregivers, and hospitals due to its high morbidity and cost. Repeated 
hospitalizations in subjects with HF are highly associated with poor subject outcomes. 
Studies report that hospitalization for HF, in itself, is one of the most important predictors 
for re-hospitalization and mortality. 2,3,4 
The ability to predict which patients will subsequently be hospitalized for HF provided the 
traditional evaluation measures such as physical signs and symptoms is limited and 
poorly associated with hemodynamics.  These methods are administered intermittently 
and may not identify patients early enough to prevent ADHF. 5 To reduce short-term 
readmission and improve chronic disease management, the integration of multiple HF 
diagnostics is required and has been shown to identify patients at a higher risk of HF 
hospitalization.5,6,7,8  Prior studies have shown implantable device-measured diagnostics 
like intra-thoracic impedance, 9 AF burden, heart rate metrics,10 respiration,11  and patient
activity metrics12 can be used individually or in a combined fashion to identify when 
patients are at risk for HF events.  We hypothesize that these measurements made in 
the subcutaneous thoracic space may be sensitive enough to detect physiological 
changes associated with ADHF. 
 
 
 
 
 
 
 
 
 
. 
For further literature review, pre-clinical testing and previous clinical experience refer to 
the Report of Prior Investigations Summary (RPIS). 
 

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5 SYSTEM DESCRIPTION AND INTENDED USE 
The study will be conducted using the components described in the table below. All 
components of the Reveal LINQ™ system are manufactured by Medtronic, Inc. 
Instructions for use of the devices used in this study are provided in their respective 
manuals or Report of Prior Investigations Summary (RPIS).  
The Reveal LINQ™ is a programmable device that continuously monitors a patient’s 
ECG and other physiological parameters. The device records cardiac information in 
response to automatically detected arrhythmias and patient activation. The LINQ™ 
device is indicated for the following: 
• 
Patients with clinical syndromes or situations at increased risk of cardiac 
arrhythmias 
• 
Patients who experience transient symptoms such as dizziness, palpitation, 
syncope and chest pain that may suggest a cardiac arrhythmia 
Table 6: System Component Information  
Model 
Number  
Component 
Manufacturer 
Investigational or Market-
released 
LNQ11 
Reveal LINQ™ Insertable 
Cardiac Monitor 
Medtronic 
Market-Released* 
LNQ11 
Incision Tool 
Medtronic 
Market-Released 
LNQ11 
Insertion Tool 
Medtronic 
Market-Released 
SW026 
2090 Programmer  
Medtronic 
Market-Released* 
Not 
Applicable 
Reveal LINQ™ RAMware 
titled: LINQ™ HF Research 
System, Rev 1.0, and 
subsequent versions as they 
are released** 
Medtronic 
Investigational 
PA96000 
Patient Assistant 
Medtronic 
Market-Released 
24950 
MyCareLink® Home Monitor 
Medtronic 
Market-Released 
DR220 
Holter 
NorthEast Monitoring, 
Inc. 
Market-Released 
*The LINQ™ device and the 2090 programmer are market-released, but once the investigational LINQ™ HF 
RAMware is downloaded into the devices, they are considered investigational. 
** Subjects will receive the most current approved version of the investigational RAMware at the time of their 
device insertion. In the case that a new RAMware version is released during the course of the study, 
subjects previously receiving an older version of the RAMware will receive an upgrade to the new version. 
 
 

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5.1 Reveal LINQ™ Insertable Cardiac Monitor (ICM) 
The Reveal LINQ™ is a leadless device that is recommended to be inserted in the 
region of the thorax. A specific recommended location is provided within the product 
manual. Two electrodes on the body of the device continuously monitor the patient’s 
subcutaneous ECG. The device can store up to 30 min of ECG recordings from the 
patient-activated episodes and up to 27 min of ECG recordings from the automatically 
detected arrhythmias. Documentation of episode occurrence will be retained.  
 
Figure 1: Reveal LINQ™ ICM 
 
5.2 Incision Tool 
The Incision Tool is designed to create an incision of repeatable width and depth with a 
single motion. It is composed of a blade, designed to make a repeatable incision, and 
handle, designed to ergonomically fit the clinician’s hand. The Reveal LINQ™ Incision 
Tool is intended to make the incision simple and repeatable. 
 
Figure 2: Incision Tool 
 
5.3 Insertion Tool 
The Insertion Tool delivers the device through the incision and into the subcutaneous 
tissue. The tool is designed to ensure the device is delivered into a tight pocket to 
maximize electrode contact with the surrounding tissue in a highly repeatable manner, 
and is composed of two parts: a handle and a plunger. The Handle is composed of a 
“channel” section, used to hold the device and guide it during insertion, and a “Tunneler,” 
used to bluntly dissect an implant path for the device to travel down while being inserted. 
The plunger part is used to push the device out of the handle, through the incision, and 
along the insertion path created by the Tunneler to the final insertion location. 
 
The Reveal LINQ™ device will be loaded in the Insertion Tool and sterile packaged with 
the Incision Tool. 
 
The Reveal LINQ™ Insertion Tool is used to create an implant path in the body, and 
deliver the Reveal LINQ™ into the desired location. 
 

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Figure 3: Insertion Tool 
5.4 2090 Programmer  
The Medtronic CareLink® Programmer is used to program the Reveal LINQ™ ICM to 
detect arrhythmias with various pre-specified characteristics. In addition, the 
programmer allows the physician to view, save, and print the ECG records currently held 
within the Reveal LINQ™ ICM. 
 
 
Figure 4: Medtronic 2090 Programmer 
The Medtronic 2090 Programmer with the LINQ™ HF investigational RAMware will be 
used to download the LINQ™ HF investigational RAMware onto the LINQ™ device.  
LINQ™ HF investigational RAMware is required to activate additional sensors in the 
Reveal LINQ™ ICM. The LINQ™ HF investigational RAMware will be loaded onto the 
2090 programmers designated for clinical use only.  The 2090 programmer with the 
LINQ™ HF investigational RAMware will allow the ability to download and remove the 
RAMware into and from the device.  In addition, the 2090 programmer will be used 
during the scheduled follow-up visits during the 6 minute hall walk test, as applicable 
 
 
 
5.5 Medtronic LINQ™ HF Investigational RAMware 
 
 
 
 

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5.6 Patient Assistant 
The Reveal Patient Assistant is a battery operated, hand-held telemetry device that 
enables the subject, on experiencing symptoms potentially indicative of a cardiac event, 
to manually trigger the LINQ™ ICM to collect and store an ECG record. 
The Reveal Patient Assistant is intended for unsupervised patient use away from a 
hospital or clinic. The Patient Assistant activates the data management feature in the 
Reveal LINQ™ ICM to initiate recording of cardiac event data in the implanted device 
memory. 
The subjects will be asked to press the Patient Assistant whenever they feel increased 
shortness of breath compared to normal. In addition, the subjects will be asked to press 
the Patient Assistant device to mark the beginning and end of their 6 Minute Hall Walk 
test ONLY when the DR220 Holter is not used. Additionally, the LINQ™ HF RAMware 
enables the storage of a short segment of impedance signal when the Reveal Patient 
Assistant device is used.  
 
 
 
Figure 5: Patient Assistant 
 
5.7 MyCareLink® Home Monitor 
The MyCareLink® Home Monitor is a device that enables the device diagnostic data 
(which includes ECG data) to be transmitted directly from the implanted Reveal LINQ™ 
device to the Medtronic CareLink® Network for review by the physician. The additional 
data that is stored in the device by the LINQ™ HF RAMware is also transmitted during a 
CareLink transmission but will not be available for review by the physician. 
 
  
Figure 6: MyCareLink® Home Monitor 
  

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5.8 DR 220 Holter Monitor 
The NorthEast Monitoring, Inc. DR220 Digital Recorder is a Holter monitor that is 
commercially available and designed to facilitate the ambulatory cardiac monitoring of 
those subjects who may benefit from such monitoring on order of a physician, including 
but not limited to those with complaints of palpitations, syncope, chest pains, shortness 
of breath, or those who need to be monitored to judge their current cardiac function, 
such as subjects who have recently received pacemakers. The DR220 Digital Recorder 
is intended for use with Medtronic System-B compatible implantable pulse generators, 
implantable cardiac defibrillators, and cardiac resynchronization therapy devices and 
implantable cardiac monitors.  A Holter monitor is an external box used to record 
electrical heart signals from electrode patches attached to the skin (ECG) as well as 
from the cardiac device (EGM).  There are no contraindications for the use of a DR220 
Holter monitor. The Holter monitor will be used in accordance with its labeling.  Only 
trained study personnel should apply the monitors.  
The data obtained by monitoring is not analyzed at the time of recording. After the 
recording is complete, the data must later be downloaded to a compatible NorthEast 
Monitoring, Inc. Holter analysis system to be analyzed. No personal information will be 
entered and collected by DR220 recorder. 
The DR220 Holter Recorder used in this study is a portable ECG device able to collect 
telemetry signals and marker channel information from any Medtronic device for up to 48 
hours. The Holter Recorder has application for any subject with a Medtronic ICM.  For 
the purposes of this study, the intended use of the Holter Recorder is to acutely uplink 
continuous 
 signals that will be collected by the LINQ™ HF RAMware in 
the Holter mode.  Since only the device data uplink feature of the Holter will be used in 
this study, the device antenna will only be used and no ECG electrodes will be used. 
 
 
 
 
 
 
Figure 7: DR220 Holter 
 
 

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6 REGULATORY COMPLIANCE 
6.1 Governing Regulations 
The Reveal LINQ™ HF study is classified as a non-significant risk (NSR) IDE study.  
The principles of the Declaration of Helsinki have been implemented in this study by 
means of the patient informed consent (PIC) process, IRB approval, study training and 
clinical trial registration. In the United States, the study will be conducted in compliance 
with 21 CFR Parts 11, 50, 54, 56 and 812. Also, local laws and regulations will be 
applicable in the countries where the study is conducted. 
This study will be conducted in compliance with international ethical and scientific quality 
standards, known as good clinical practice (GCP). GCP includes review and approval by 
an independent IRB before initiating a study, continuing review of an ongoing study by 
IRBs, and obtaining and documenting the freely given informed consent of a subject 
before initiating the study. 
The study will be publicly registered prior to first enrollment in accordance with the 2007 
Food and Drug Administration Amendments Act (FDAAA) and Declaration of Helsinki on 
http://clinicaltrials.gov (PL 110-85, Section 810(a) 
6.2 Institutional Review Board 
Before enrolling subjects in the study, IRB approval of study documents including the 
CIP and PIC is required. IRB approval is required for all sites. IRB approval must be 
received in the form of a letter and provided to Medtronic before commencement of the 
study at a study center. The approval letter must contain enough information to identify 
the version or date of the documents approved. 
6.3 CIP/CIP Amendments 
Approval of the CIP is required from the following groups prior to any study procedures 
at a study center:  
• 
Medtronic  
• 
An independent institutional review board  
Similarly, approval of subsequent revisions to the CIP is required at each study center 
from the above mentioned groups prior to implementation of the revised CIP at that 
center. 
6.4 Subject Materials 
Each center’s IRB will also be required to approve any subject facing materials that may 
be used in the study, if applicable. 
 
 
 

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7 METHODOLOGY 
7.1 Study Design 
The Reveal LINQ™ HF study is a prospective, non-randomized, multi-center, 
observational, pre-market clinical study.  The study is expected to be conducted at up to 
30 centers in the United States. Up to 300 subjects will be enrolled to achieve 
approximately 40 heart failure events (no more than two per subject contribute to the 
cumulative total). Study subjects will be followed for up to 3 years post-insertion or until 
official study closure defined as when Medtronic and/or regulatory requirements have 
been satisfied per the Clinical Investigation Plan and/or by a decision by Medtronic or 
regulatory authority, whichever occurs first.  Accordingly, the expected total study 
duration is approximately 4 years, representing approximately 1.5 years of patient 
enrollment and 2.5 years of subject follow-up. All Reveal LINQ™ system and procedure-
related adverse events will be collected and reported per the study protocol. 
7.2 Objective 
7.2.1 Primary objective 
The primary objective is to characterize Reveal LINQ™ derived data from patients with 
heart failure by assessing the relationship between changes in LINQ™ derived data and 
other physiologic parameters with subsequent ADHF events. 
7.3 Subject Selection Criteria 
Patients will be screened to ensure they meet all of the inclusion and none of the 
exclusion criteria prior to study enrollment. IRB approval of the Reveal LINQ™ Heart 
Failure (HF) Clinical Study including required documents (e.g. Clinical Investigation Plan, 
Patient Informed Consent Form, etc.) must be obtained prior to enrolling patients in the 
study. 
7.3.1 Inclusion criteria 
• 
Patient is 18 years of age or older 
• 
Patient (or patient’s legally authorized representative) is willing and able to 
provide written informed consent 
• 
Patient is willing and able to comply with the protocol, including follow-up visits 
and Carelink transmissions 
• 
Patient has NYHA Class III, per most recent assessment or at any time within 30 
days prior to enrollment  
• 
Patient had a HF event (HF event defined as meeting any one of the following 
three criteria): 
1. Admission with primary diagnosis of HF within the last 6 months, OR 
2. Intravenous HF therapy (e.g. IV diuretics/vasodilators) or ultrafiltration at any 
one of the following settings within the last 6 months: 
- 
Admission with secondary/tertiary diagnosis of HF 
- 
Emergency Department 

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- 
Ambulance 
- 
Observation Unit 
- 
Urgent Care 
- 
HF/Cardiology Clinic 
- 
Patient’s Home, OR 
3. Patient had the following BNP/NTpro-BNP within the last 3 months:  
- 
If EF ≥ 50%, then BNP> 200 pg/ml or NTpro-BNP > 400 pg/ml OR 
- 
If EF is <50%, then BNP> 400 pg/ml or NTpro-BNP > 800 pg/ml 
7.3.2 Exclusion criteria 
• 
Patient is pregnant (all females of child-bearing potential must have a negative 
pregnancy test within 1 week of enrollment)  
• 
Patient is enrolled in another study that could confound the results of this study, 
without documented pre-approval from a Medtronic study manager 
• 
Patient has severe valvular heart disease as defined by hemodynamically 
significant valve stenosis and/or prosthetic heart valve 
• 
Patient has existing IPG, ICD, CRT-D or CRT-P device 
• 
Patient has severe renal impairment (eGFR <25mL/min) 
7.4 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): 
• 
Patients will be screened to confirm eligibility for enrollment in keeping with the 
inclusion/exclusion criteria 
• 
Subject demographics will be collected at baseline on possible differences that 
may affect the study results 
• 
To ensure a widespread distribution of data between centers, the maximum 
number of enrollments per center is 60 subjects 
• 
A maximum of two heart failure events per subject will be used towards the 
primary objective 
• 
Regular monitoring visits will be conducted for adherence to the CIP and to verify 
source data 
• 
All study clinicians, participating site personnel, and Medtronic personnel will be 
trained on their respective aspects of the study using standardized training 
materials 
• 
All centers will use the same version of the Clinical Investigation Plan (CIP) and 
electronic Case Report Forms (eCRF) 
• 
An independent Clinical Events Committee (CEC) will be used to regularly review 
and adjudicate reported adverse events, healthcare utilizations and deaths 
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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8 STUDY PROCEDURES 
Prior to performing study related procedures, all sites must have IRB approval as well as 
documentation from Medtronic of center readiness. 
The study by design requires a close collaboration between the heart failure specialist 
and LINQ™ implanters at each participating center.  All implanting physicians must be 
experienced in the handling of Reveal LINQ™ devices.  
8.1 Investigator and Site Selection Criteria 
All clinical investigators managing the subject’s heart failure must be qualified 
practitioners and experienced in the management of patients with heart failure. All 
implanting physicians must be experienced in the handling of Reveal LINQ™ devices.  
The role of the principal investigator is to implement and manage the day-to-day conduct 
of the clinical investigation as well as ensure data integrity and the rights, safety and 
well-being of the subjects involved in the clinical investigation. 
The principal investigator shall: 
• 
Be qualified by education, training, and experience to assume responsibility for 
the proper conduct of the clinical investigation 
• 
Be experienced in the management of heart failure patients. 
• 
Disclose potential conflicts of interest, including financial, that interfere with the 
conduct of the clinical investigation or interpretation of results   
The principal investigator shall be able to demonstrate that the proposed investigational 
site: 
• 
Has the required number of eligible subjects needed within the recruitment period 
• 
Has one or more qualified investigators, a qualified investigational site research 
team and adequate facilities for the foreseen duration of the clinical investigation 
Center personnel training will be completed prior to participation in this clinical study. 
 
8.2 Site Activation  
During the activation process (prior to subject enrollment), Medtronic will train site 
personnel on the clinical investigation plan, relevant standards and regulations, if 
needed, informed consent and on data collection and reporting tools. If new members 
join the study center team, they will receive training on the applicable clinical study 
requirements relevant to their role before contributing to the clinical study. 
Prior to performing study related activities, all local regulatory requirements shall be 
fulfilled, including, but not limited to the following:  
• 
IRB approval of study documents including the current version of the CIP and 
Patient Informed Consent.  
• 
Regulatory authority approval or notification (as required per local law)  
• 
Fully executed Clinical Trial Agreement (CTA)  
• 
Financial Disclosure   
• 
Curriculum Vitae (CV) of investigators  

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• 
Documentation of delegated tasks 
• 
Documentation of study training 
Additional requirements imposed by the IRB and regulatory authority shall be followed, if 
appropriate.  
In addition, all participating site staff must be trained on the current version of the CIP 
and must be delegated by the principal investigator to perform study related activities.   
Medtronic will provide each study center with documentation of study center/investigator 
readiness; this letter must be received prior to subject enrollment. 
8.3 Equipment Requirements 
The following equipment must be available at each center to support study activities: 
• 
Computer with high speed internet access using Microsoft Internet Explorer for 
data entry (version 6 or 8 or other compatible version) 
• 
Market-released Medtronic programmer (Model 2090) 
• 
Blood draw including BNP or NT-proBNP analysis capabilities at a certified local 
lab          
Medtronic will supply additional Patient Assistant devices for use at the in-office   
follow-up visits to mark the beginning and end of the 6 minute hall walk test ONLY when 
the DR220 Holter is not used. 
8.4 Data Collection 
Clinical data are collected at designated time points throughout the study. A web-based 
application tool, Remote Data Capture (RDC) will be used for data entry. This tool has 
Electronic Case Report Forms (eCRFs) which can be accessed via an Internet browser. 
Data will be processed using an electronic data management system for clinical studies. 
Data will be stored in a secure, password protected database which will be backed up on 
a daily basis. Data will be reviewed using programmed and manual data checks. Data 
queries will be made available to study centers for resolution. Study management 
reports will be generated to monitor data quality and study progress. The investigator is 
responsible for the preparation (review and signature) of the eCRFs. At the end of the 
study, the data will be frozen and retained indefinitely by Medtronic. The requirements 
for data collection and study visit schedules are summarized in Table 6. 
 
 
 
 
 
 

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Table 7: Data Collection and Study Procedure Requirements at Subject Visits 
*DR220 Holter is recommended at the 6 Month Visits. 
 
8.5 Role of the Sponsor Representatives 
Medtronic personnel may provide support as required for the study under supervision of 
the Principal Investigator, including: 
 
• 
Provide study training relevant and pertinent to the involvement of personnel 
conducting study activities and investigator responsibilities 
• 
Technical support at device insertion and follow-up visits under the supervision of 
a study investigator, but no data entry on the case report forms, shall be 
performed by Medtronic personnel or their representatives at sites 
STUDY PROCEDURE 
Baseline 
LINQ Insertion 
1 Mo Visit 
6 Mo and 12 
Mo Office 
Visit 
Device 
Transmission/  
HCU Monthly 
Call 
Study Exit 
Patient Informed Consent 
X 
 
 
 
 
 
Inclusion/Exclusion Assessment 
X 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
Demographics  
X 
 
 
 
 
 
Physical Exam 
X 
 
X 
X 
 
 
Medication Assessment 
X 
 
X 
X 
 
X 
Laboratory results 
X 
 
 
X 
 
 
Symptoms and Temperature (via ear is recommended) 
 
 
X 
X 
 
 
Final system configuration 
 
X 
 
 
 
 
Insertion procedure information 
 
X 
 
 
 
 
LINQ™ HF RAMware download onto LINQ™ device 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
Device Data  
 
X 
X 
X 
X 
X 
NYHA functional classification assessment 
 
 
X 
X 
 
 
6 minute hall walk test 
 
 
X 
X 
 
 
Holter (DR220) with 6 Minute Hall Walk Test (Recommended) 
 
 
 
X* 
 
 
 
 
 
X 
X 
 
 
LINQ™ HF RAMware removal from LINQ™ device 
 
 
 
 
 
X 
Adverse Event 
As Occurs 
Healthcare Utilization 
Device Deficiency 
System Modification 
Study Deviations 
Death 

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• 
Monitoring and auditing activities 
8.6 Patient Informed Consent Process 
Patient informed consent (PIC) is defined as a legally effective documented confirmation 
of a subject’s or their legally authorized representative voluntary agreement to 
participate in a particular clinical study after information has been given to the subject on 
all aspects of the clinical study that are relevant to the subject’s decision to participate. 
This process includes obtaining a Patient Informed Consent Form and a/an 
Authorization to Use and Disclose Personal Health Information/Research 
Authorization/other privacy language as required by law that has been approved by the 
study center’s IRB Committee and signed and dated by the subject or their legally 
authorized representative. A subject may only consent after information has been given 
to the subject on all aspects of the clinical investigation that are relevant to the subject’s 
decision to participate. Informed consent may be given by the legally authorized 
representative only if a subject is unable to make the decision to participate in a clinical 
investigation. In such cases, the subject shall also be informed about the clinical 
investigation within his/her ability to understand. 
Prior to enrolling subjects, each center’s IRB will be required to approve the PIC Form 
and the Authorization to Use and Disclose Personal Health Information/Research 
Authorization/other privacy language as required by law.  The document(s) must be 
controlled (i.e. versioned and/or dated) to ensure it is clear which version(s) were 
approved by the IRB.  Any adaptation of the sample Patient Informed Consent Form 
must be reviewed and approved by Medtronic and the IRB reviewing the application 
prior to enrolling subjects.  
The investigator must notify the subject or their legally authorized representative of any 
significant new findings about the study that become available during the course of the 
study which are pertinent to the safety and well-being of the subject, as this could impact 
a subject’s willingness to participate in the study. If relevant, approval may be requested 
from subjects to confirm their continued participation. 
Refer to Appendix D for the sample Patient Informed Consent Form Template. 
Prior to initiation of any study-specific procedures, patient informed consent must be 
obtained from the subject or their legally authorized representative. Likewise, privacy or 
health information protection regulation may require subjects to sign additional forms to 
authorize centers to submit subject information to the study sponsor. The informed 
consent process must be conducted by the principal investigator or an authorized 
designee, and the Patient Informed Consent Form and Authorization to Use and 
Disclose Personal Health Information/Research Authorization/other privacy language as 
required by law must be given to the subject (or their legally authorized representative) 
in a language he/she is able to read and understand. The process of patient informed 
consent must be conducted without using coercion or undue improper influence on or 
inducement of the subject to participate by the investigator or other center personnel. 
The informed consent process shall not wave or appear to waive subject’s legal right. 
The language used shall be as non-technical as possible and must be understandable to 
the subject and the impartial witness, where applicable.  
The subject must have ample time and opportunity to read and understand the Patient 
Informed Consent Form, to inquire about details of the study, and to decide whether or 

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not to participate in the clinical study. All questions about the study should be answered 
to the satisfaction of the subject. 
When the subject decides to participate in the clinical study, the PIC must be signed and 
personally dated by the subject and investigator or authorized designee, as required by 
the Patient Informed Consent Form. If applicable, the witness shall also sign and 
personally date the Patient Informed Consent Form to attest that the information in the 
PIC was accurately explained and clearly understood by the subject, and that informed 
consent was freely given. 
A copy of the Patient Informed Consent Form and the Authorization to Use and Disclose 
Personal Health Information/Research Authorization/other privacy language, signed and 
dated as required by law, must be provided to the subject.  
If the Patient Informed Consent Form is obtained the same day the subject begins 
participating in study-related procedures, it must be documented in the subject’s case 
history that consent was obtained prior to participation in any study-related procedures. 
It is best practice for the informed consent process to be documented in the subject’s 
case history, regardless of circumstance. 
In the event the subject cannot read and/or write, witnessed (impartial third party) patient 
informed consent will be allowed, provided detailed documentation of the process is 
recorded in the subject’s case history and the witness signs and dates the Patient 
Informed Consent Form. The subject should “make his mark” (sign or otherwise 
physically mark the document so as to indicate consent) on the PIC as well. The Patient 
Informed Consent Form should document 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.  
The original of the signed Patient Informed Consent Form must be filed in the hospital 
/clinical chart and/or with the subject’s study documents.  
The Patient Informed Consent Form and Authorization to Use and Disclose Personal 
Health Information/Research Authorization/other privacy language as required by law 
must be available for monitoring and auditing. Any Medtronic Field personnel who 
support the Reveal LINQ™ insertion must be able to review the subject’s signed and 
dated Patient Informed Consent Form and verify its completeness prior to proceeding 
with the LINQ™ insertion/download. In the event the Medtronic Field personnel identify 
the patient informed consent as being incomplete, the Reveal LINQ™ insertion will not 
be allowed to occur until the consent of the subject can be adequately and appropriately 
obtained.  
8.7 Enrollment  
When a patient and the principal investigator or authorized designee have personally 
signed and dated the Patient Informed Consent Form, the patient is considered a subject 
enrolled in the study. The date the subject signed the Patient Informed Consent Form 
and data protection authorization must be documented in the subject’s medical records. 
8.8 Baseline  
The Baseline visit can be a standalone visit or can be performed on the same day of 
LINQ™ Insertion prior to the LINQ™ Insertion procedure. 

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The following information is required to be collected at the baseline visit: 
• 
Patient Informed Consent Form 
• 
Inclusion/Exclusion Criteria assessment (including pregnancy test if the subject is 
of child bearing potential) 
• 
Medical History including most recent EF (if available in the last 6 months) and 
previous heart failure events in the last 6 months. 
• 
Demographics 
• 
Physical exam  
• 
Medications 
• 
Laboratory results: BNP, eGFR, Blood Urea Nitrogen (BUN), Serum Creatinine, 
Sodium (Na), Potassium (K), Hemoglobin (Hb), Hematocrit (Hct), Troponin 
• 
Any healthcare utilizations 
• 
Study deviations  
8.9 Insertion  
Within 30 working days of the baseline assessment, the Reveal LINQ™ device will be 
inserted in the subject. The insertion procedure will be performed in accordance with the 
Medtronic Reveal LINQ™ implant instructions.  After the Reveal LINQ™ device is 
inserted, the LINQ™ HF investigational RAMware will be downloaded to the device via 
the 2090 programmer. Use of the recommended implant locations is located in Figure 8 
below. Physicians should follow the implant manuals when performing the Reveal 
LINQ™ implant.  
 
 
 
Figure 8: Recommended Insertion Locations 
 
 
 

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The following information is required to be collected at the insertion visit: 
• 
Final system configuration 
• 
Insertion procedure information 
• 
LINQ™ HF Investigational RAMware download 
• 
 
• 
Device interrogation (media/USB) 
• 
Any Reveal LINQ™ system and procedure-related adverse events   
• 
Any healthcare utilizations 
• 
Any device deficiencies or study deviations  
8.9.1 Programming Recommendations 
Once the LINQ™ device is inserted into the subject, the physician is recommended to 
choose "AF management.” This will automatically program the device to the nominal 
settings for the different detectors.  
8.10 Scheduled Follow-up visits 
After receiving notice of successful LINQ™ insertion, Medtronic will provide the target 
dates and windows for each visit to the implanting center. Should a subject miss a visit 
or the visit fall outside the pre-specified window, a study deviation must be reported and 
the original follow-up schedule maintained for subsequent visits.  
Data analyses include follow-up visits, regardless of whether the visit occurs within the 
window.   Therefore, a late visit is preferred over a missed visit but must be 
accompanied by a deviation. Follow-up visit windows are listed in Table 7 and are based 
on days post-insertion. 
Table 8: Post-Insertion Follow-up Windows  
Study Follow-up 
Visit 
Window 
(Calculated days post-procedure attempt) 
Window Start 
(# of days) 
Target 
(# of days) 
Window End 
(# of days) 
1 month 
30 
30 
37 
6 month 
163 
183 
203 
12 month 
345 
365 
385 
 
The following information is required to be collected at the 1 Month scheduled follow-up 
visits: 
• 
Physical exam including temperature 
• 
Symptoms review 
• 
Medications 
• 
NYHA assessment 
• 
6 Minute Hall Walk test 
• 

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• 
Device interrogation (media/USB) 
• 
Any Reveal LINQ™ system and procedure-related adverse events   
• 
Any healthcare utilizations  
• 
Any device deficiencies or study deviations  
The following information is required to be collected at the 6 Month and 12 Month 
scheduled follow-up visits: 
• 
Physical exam including temperature 
• 
Symptoms review 
• 
Medications 
• 
NYHA assessment 
• 
6 Minute Hall Walk test (DR220 Holter recommended to be used at 6 Month Visit 
Only during the 6 Minute Hall Walk test) 
• 
 
• 
Laboratory results: BNP, eGFR, Blood Urea Nitrogen (BUN), Serum Creatinine, 
Sodium (Na), Potassium (K), Hemoglobin (Hb), Hematocrit (Hct), Troponin 
• 
Device interrogation (media/USB) 
• 
Any Reveal LINQ™ system and procedure-related adverse events   
• 
Any healthcare utilizations  
• 
Any device deficiencies or study deviations  
8.11 Device Transmission/ HCU Monthly Call (Start within Month 1) 
There will be a Monthly Device Transmission eCRF to be completed starting within the 
first month from insertion. This visit will be conducted to ensure the subject manually 
transmitted the device data (see section 8.12 below). In addition, a HCU assessment will 
be completed in cases where the subject is contacted. Subjects should be contacted 
regularly (recommended at least every 3 months) regardless of manual transmission 
status to ensure complete and timely reporting of HCUs. Follow-up windows will vary 
based on the timing of the most recent device interrogation/transmission and will be 
provided by Medtronic as needed. 
8.12 Monthly CareLink Transmissions  
Subjects are required to perform a manual device transmission monthly from the time 
they are enrolled in the study until their Study Exit visit.
 
  The subject will utilize the MyCareLink® Home Monitor to manually 
transmit the data. The subject will receive instructions on how to perform the manual 
transmission. Refer to Appendix G. 
As described above, a Monthly Device Transmission eCRF will be required to be 
completed to ensure the subject manually transmitted. A study deviation will be required 
for any missed monthly manual Carelink transmissions, unless a device interrogation file 
for an interrogation occurring within the required timeframe is provided to Medtronic. 

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8.13 Device Interrogation 
For all follow-up visits occurring in the office, a full “interrogate all” final device 
interrogation file (.pdd) must be obtained and saved in a digital format (USB). The 
original file must be stored at the site and a copy sent to Medtronic. It is recommended 
that data are not cleared during any interrogation. This should be conducted at the end 
of the visit. 
8.14 Healthcare Utilization 
Cardiovascular-related Health Care Utilizations (HCUs) (including hypervolemia and 
hypovolemia) will be collected.  This includes the following: 
• 
Unscheduled clinic visit (including subject-initiated phone calls if the subject is 
experiencing CV-related symptoms) 
• 
Scheduled clinic visit (if the subject is experiencing CV-related symptoms) 
• 
Hospital outpatient clinic visit 
• 
Urgent care visit 
• 
Other outpatient utilization with overnight stay 
• 
Emergency department visit 
• 
Inpatient hospitalization 
HCU information should be reported upon center awareness and assessed at all visits 
including the monthly telephone visits. If multiple HCUs occur within the same day, data 
from all HCUs can be captured on one eCRF. 
8.15 System Modification 
A system modification will be reported in the event the device requires invasive 
modification (e.g., device explant, device reposition).  In the event of a system 
modification, the follow-up schedule for the subject will remain unchanged. For a system 
modification the following activities are required: 
• 
Complete the System Modification eCRF 
• 
Device interrogation (media/USB) 
• 
Any Reveal LINQ™ system and procedure-related adverse events   
• 
Any healthcare utilizations 
• 
Any device deficiencies or study deviations  
If the device is taken out of service (e.g, explanted) and a replacement will not be 
implanted or the replacement is not a study approved device, the subject must be exited 
from the study after all device and/or procedure related AEs have been resolved or 
remain unresolved with no further action planned. 
All explanted product (device) should be returned to Medtronic for analysis when 
permissible by local laws and regulations. See Section 9 for final product disposition 
details. 

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In the event that a subject has a re-attempt after a previous unsuccessful system 
modification, the subsequent attempt(s) must be reported via eCRF as separate system 
modifications. 
8.16 Study Exit 
A Study Exit eCRF is required for all subjects except in the case of death. Prior to exiting 
a subject from the study, it is recommended to follow the subject until all ongoing device 
and/or procedure related AEs are resolved or unresolved with no further actions 
planned.  Following exit, subjects will continue to receive standard medical care.  Upon 
exiting from the study, no further study data will be collected or study visits will occur for 
the subject. All data available through the time of the subject’s exit will be used for 
analysis.  
Subjects are urged to remain in the study as long as possible but may be exited from the 
study for any of the following situations and will be documented on the Study Exit eCRF: 
• 
Subject did not meet inclusion/exclusion criteria  
• 
Subject was not inserted with a Reveal LINQ™ device 
• 
Reveal LINQ™ removal without re-implantation  
• 
Implant attempted, however no Reveal LINQ™ was implanted 
• 
Subject relocation to another geographic location 
• 
Subject chooses to withdrawal  
• 
Investigator chooses to withdraw a subject 
• 
Subject lost to Follow-Up 
• 
End of battery life of LINQ™ device 
• 
Study Termination 
The following information/procedure is to be collected/performed at study exit: 
• 
Reason for exit 
• 
Removal of the LINQ™ HF investigational RAMware from the LINQ™ device 
• 
Medications 
• 
Device interrogation (media/USB) 
• 
Any Reveal LINQ™ system and procedure-related adverse events   
• 
Any healthcare utilizations 
• 
Any device deficiencies or study deviations  
In the case that the subject is determined to be lost to follow-up, details of a minimum of 
two attempts and the method of attempt (e.g., one letter and one phone record or two 
letters) to contact the subject must be recorded. In addition, follow the regulations set 
forth by the governing IRB.  
If discontinuation is because of safety or lack of effectiveness, the subject shall be asked 
to be followed for collecting safety data outside the clinical investigation. 

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8.17 Medications 
Cardiovascular medications will be collected at the baseline assessment, 1 Month, 6 
Month, 12 Month office visits and Study Exit. The name, dose, frequency and route of all 
cardiovascular medications will be collected. Changes to medications will be captured at 
healthcare utilizations. 
There are no medications that are required for this study although some medications 
may be administered in treating specific conditions at the discretion of the physician. The 
only medications that are excluded from use during this study are investigational. 
8.18 6 Minute Hall Walk Test 
Subjects will be asked to perform a 6 Minute Hall Walk test at the 1 Month, 6 Month and 
12 Month office visits. A Holter will be recommended to be worn during the 6 Minute hall 
walk at the 6 Month Visit only. In addition, the subjects will be asked to press the Patient 
Assistant device to mark the beginning and end of their 6 Minute Hall Walk test ONLY 
when the DR220 Holter is not used. Refer to Appendix C for more details. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.21 Review of Data Recorded by the Reveal LINQ™ Device 
Reveal LINQ™ data derived from the LINQ™ HF investigational RAMware will not be 
viewable to the site.  The standard arrhythmia data from the LINQ™ device will be 
viewable via Carelink. 
8.22 Holter 
Subjects may be asked to have a Holter placed to collect some additional information 
from the LINQ™ device.  The DR220 Holter Recorder used in this study is a portable 
ECG device able to collect continuously telemetered signals from any Medtronic device 
for up to 48 hours. The Holter Recorder has application for any subject with a Medtronic 
ICM.  For the purposes of this study, the intended use of the Holter Recorder is to 
acutely uplink continuous 
signals that will be collected by the LINQ™ 
HF RAMware in the Holter mode.  The intended use of Holter mode is for a short 
duration of less than 30 minutes during the 6 minute hall walk test during an office visit.  

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Since only the device data uplink feature of the Holter will be used in this study, the 
device antenna will only be used and no ECG electrodes will be used.  Please refer to 
Appendix C for more details. 
 
 

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9 INVESTIGATIONAL DEVICE/RAMWARE STORAGE, 
HANDLING AND TRACEABILITY 
The following section details tracking of all clinical investigation study components. 
Study components will be distributed to a center only when Medtronic has received all 
required documentation and has notified the center of center activation. 
Distribution of study components to study centers during the clinical study will be 
managed by Medtronic. All product must be stored in a secure location at the site. It is 
the responsibility of the investigator to correctly handle, store, and track the study 
products maintained at the site. Study components will be used only in the study 
according to the CIP. 
Product Distribution logs may be located in the database and will be used for tracking of 
products during and after the study. The logs must be updated when product is received, 
opened, implanted, explanted, disposed of or returned to Medtronic. The disposition log 
tracks product information including, but not limited to, date, model/serial number, and 
expiration date for received product, subject ID of implanted subject, date implanted, 
date explanted (if applicable), date returned to Medtronic and reason for return (if 
applicable), reason for and method of destruction/disposal for explanted components not 
returned to Medtronic (if applicable), and name of person responsible for return or 
destruction/disposal (if applicable).  Medtronic will perform periodic reconciliation of 
investigational product to ensure traceability.  
The following products will be tracked on a disposition log: 
• 
Reveal LINQ™ device 
• 
2090 Programmer with the LINQ™ HF investigational RAMware 
• 
Patient Assistants provided to sites for use during in-office visits 
• 
Holter DR220 
The 2090 Programmers used in the study are commercially available, however once 
the LINQ™ HF investigational RAMware is downloaded onto the 2090 Programmers in 
this study, the 2090 Programmer becomes investigational. The 2090 Programmer 
disposition logs will be located in the database and will be used for tracking of all 
programmers downloaded with LINQ™ HF investigational RAMware. When the LINQ™ 
HF investigational RAMware is installed on or removed from the programmer(s), the 
programmer disposition log must be updated. 
The Reveal LINQ™ device used in this study are commercially available, however once 
the LINQ™ HF investigational RAMware is downloaded to the device, the device will be 
considered an investigational product. The investigational device will be tracked via 
device disposition logs in the database. When the LINQ™ HF investigational RAMware 
is installed on or removed from the device(s), these changes must be recorded on the 
applicable eCRF(s) (e.g. Insertion Procedure, Scheduled Follow-up or Study Exit eCRF). 
9.1 Medtronic Supplied Equipment Accountability 
All explanted product should be returned to Medtronic for analysis according to local 
laws and regulations. If the products are explanted but not returned, a justification is 

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required to be reported on the appropriate eCRF(s) and/or disposition log(s). The 
Product Distribution Logs must be updated for explanted devices. To receive a Returned 
Product Mailer Kit, please contact your local Medtronic personnel or Study Manager. All 
unused product must be returned to Medtronic upon study closure at the center. 
The Product Disposition Logs must be updated with the final device disposition. 
Table 9: Final Disposition of Products 
Model 
Number 
Component 
 
Return to MDT at 
Center closure 
 
Disposal 
after Each 
Use 
LINQ™ HF 
Investigational 
RAMware 
Removal 
LNQ11 
Reveal LINQTM 
X  
(Explant Only) 
 
X              
(Study Exit) 
24950 
MyCareLink® Monitor 
Return Not Required – Market Released 
96000 
Patient Assistant* 
Return Not Required – Market Released* 
2090  
2090 Programmer 
with LINQ HF 
Research System, 
Rev 1.0 RAMware (or 
subsequent version) 
X1 
 
X 
DR220 
Holter 
X 
 
 
1 If the 2090 programmer was supplied to the site for purposes of the study, the 2090 
programmer should be returned to Medtronic. 
 
All product returns will be contingent on local laws and regulations. 
 
All Investigational Product will be labeled Investigational. 
*Patient Assistants that will be used at the sites are required to be returned to Medtronic at the end 
of the study. 
9.1.1  Shipment of Study Components 
Medtronic will only allow shipment of the study device and components to the hospital or 
investigator when Medtronic has received all required documentation and has notified 
the site of readiness. Products shall be used in these centers only and according to the 
CIP. Clinical investigational devices and components that are used for purposes of the 
study only will be provided at no cost by Medtronic. Distribution of the study device and 
components to centers during the study will be managed by Medtronic. 
All investigational components must be stored in a secure location in which access is 
limited to authorized personnel only. 
9.1.2 Storage and Handling of Study Device and Components 
It is the responsibility of the investigator to store the study specific components and 
study specific equipment in a secured and temperature controlled area. The method of 
storage shall prevent the use of the study device and components for other applications. 
Opening sealed cases is forbidden for other than study use and must be reported to the 
Investigator and Sponsor upon detection. 

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10 STUDY DEVIATIONS 
A study deviation is defined as an event within a study that did not occur according to 
the Clinical Investigation Plan or the Clinical Trial Agreement. 
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 visits, inadvertent loss of data due to computer 
malfunction, inability to perform required procedures due to subject illness). 
For medically justifiable conditions which preempt a subject’s ability to complete a study-
required procedure, it may be permitted to report only one deviation which will apply to 
all visits going forward. This may also apply for other unforeseen situations (e.g. the 
subject permanently refuses to complete a study required procedure and the data will 
not contribute to the primary end point analysis). However, prior approval from Medtronic 
is required for such situations.  
All study deviations must be reported on the Case Report Form regardless of whether 
medically justifiable, pre-approved by Medtronic, an inadvertent occurrence, or taken to 
protect the subject in an emergency. Multiple deviations of the same type at the same 
visit may be reported on one case report form. In the occurrence of a corrupted device 
interrogation file, Medtronic may request a deviation to document that a readable 
interrogation file is unavailable. 
In the event the deviation involves a failure to obtain a subject’s consent, or is made to 
protect the life or physical well-being of a subject in an emergency, the deviation must be 
reported to the IRB as well as Medtronic within five (5) working days. Reporting of all 
other study deviations should comply with IRB policies and/or local laws and must be 
reported to Medtronic as soon as possible upon the center becoming aware of the 
deviation. Reporting of deviations must comply with IRB policies, local laws, and/or 
regulatory agency requirements.  Refer to Investigator Reports, Table 15 for deviation 
reporting requirements and timeframes for reporting to Medtronic and/or regulatory 
bodies.  
Medtronic is responsible for analyzing deviations, assessing their significance, and 
identifying any additional corrective and/or preventive actions (e.g. amend the Clinical 
Investigation Plan, conduct additional training, terminate the investigation). Repetitive or 
serious investigator compliance issues may result in initiation of a corrective action plan 
with the investigator and site, and in some cases, necessitate suspending enrollment 
until the problem is resolved or ultimately terminating the investigator's participation in 
the study. Medtronic will provide center-specific reports to investigators summarizing 
information on deviations that occurred at the investigational site on a periodic basis.  
 
 
 

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11 ADVERSE EVENTS AND DEVICE DEFICIENCIES 
Timely, accurate, and complete reporting and analysis of safety information for clinical 
studies are crucial for the protection of subjects. Reporting and analysis of safety data 
are mandated by regulatory authorities worldwide. Medtronic has established 
procedures in conformity with regulatory requirements to ensure appropriate reporting of 
safety information. This study is conducted in accordance with these procedures and 
regulations. 
11.1 Adverse Event and Device Deficiency Definitions 
Where the definition indicates “device”, it refers to any device used in the study. This 
might be the device under investigation, or any market released component of the 
system. 
Table 10: Adverse Event Definitions 
General 
Adverse Event (AE) 
(Adapted from ISO 14155:2011, 3.2)  
Any untoward medical occurrence, unintended disease or injury, 
or untoward clinical signs (including abnormal laboratory findings) 
in subjects, users or other persons, whether or not related to the 
investigational medical device 
 
NOTE 1: This definition includes events related to the 
investigational medical device or the comparator. 
NOTE 2: This definition includes events related to the procedures 
involved. 
 
Adverse Device Effect (ADE) 
(ISO 14155:2011, 3.1) 
Adverse event related to the use of an investigational medical 
device 
 
NOTE 1: This definition includes adverse events resulting from 
insufficient or inadequate instructions for use, deployment, 
implantation, installation, or operation, or any malfunction of the 
investigational medical device. 
NOTE 2: This definition includes any event resulting from an error 
use or from intentional misuse of the investigational medical 
device.  
Device Deficiency (DD) 
(ISO 14155:2011, 3.15) 
Inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety or performance.  
 
NOTE 1: Device deficiencies include malfunctions, use errors and 
inadequate labeling  
Relatedness 
 Procedure Relatedness 
An adverse event that occurs due to any procedure related to the 
insertion or surgical modification of the Reveal LINQ™ device 
 
Reveal LINQ™ System Relatedness 
An adverse event that results from the presence or performance 
of any component of the Reveal LINQ™ system (including the 
LINQ™ device, incision/insertion tools, patient assistant and 
programmer)  
Seriousness 

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Serious Adverse Event (SAE) 
(ISO 14155:2011, 3.37) 
Adverse event that 
a) led to death, 
b) led to serious deterioration in the health of the subject, that 
either resulted in 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body 
function, or 
3) in-patient or prolonged hospitalization, or 
4) medical or surgical intervention to prevent life-threatening 
illness or injury or permanent impairment to a body structure or 
a body function, 
c) led to foetal distress, foetal death or a congenital abnormality 
or birth defect 
 
NOTE 1: Planned hospitalization for a pre-existing condition, or a 
procedure required by the CIP, without serious deterioration in 
health, is not considered a serious adverse event. 
 
 
Serious Adverse Device Effect (SADE) 
(ISO 14155:2011, 3.36) 
Adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event. 
 
Complication 
An adverse event that includes the following is considered a 
complication: 
 Results in death,
 
 Involves any termination of
 significant
 device function, or
 
 R e q u 
ire s  a n 
 in va s 
ive  in 
te rve n 
tio n
 
 
(21 CFR 812) Non-invasive: 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 noninvasive, and the use of surplus 
samples of body fluids or tissues that are left over from samples 
taken for non-investigational purposes is also considered 
noninvasive. 
 
Observation 
Any adverse event that is not a complication. 
 
Unanticipated Adverse Device Effect 
(UADE) 
(21 CFR 812.3(s)) 
Any serious adverse effect on health or safety or any life-
threatening problem or death caused by, or associated with, a 
device, if that effect, problem, or death, was not previously 
identified in a nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan 
or application), or any other unanticipated serious problem 
associated with a device that relates to the rights, safety, or 
welfare of subjects.  
Other 

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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 
Pocket site / Incisional pain 
72 
Mild to moderate bruising / ecchymosis 
168 
 
11.2 Adverse Event and Device Deficiency Assessment 
11.2.1 Adverse Events 
Reveal LINQ™ system and procedure-related adverse events will be collected 
throughout the study duration, starting at the time of signing the Patient Informed 
Consent Form. Reporting of these events to Medtronic will occur on an Adverse Event 
(AE) Form, including a description of AE, date of onset of AE, date of awareness of site, 
treatment, resolution, assessment of both the seriousness and the relatedness to the 
investigational device. Each AE must be recorded on a separate AE Form. Subject 
deaths are also required to be reported on a Subject Death form. Refer to section 11.6 
for Subject Death collection and reporting requirement 
Documented pre-existing conditions are not considered AEs unless the nature or 
severity of the condition has worsened. The unavoidable Adverse Events, listed in Table 
9 need not be reported unless the adverse event worsens or is present outside the 
stated timeframe post-implant. For AEs that require immediate reporting (refer to Table 
11), initial reporting may be done by phone, fax, or on the eCRF completing as much 
information as possible. The AE eCRF must be completed as soon as possible.  
11.2.2 Device Deficiencies 
Device deficiency information will be collected throughout the study and reported to 
Medtronic. Note that device deficiencies that result in an adverse device effect (ADE) to 
the subject should be captured on an Adverse Event form only. 
11.2.3 Processing Updates and Resolution 
For any changes in status of a previously reported adverse event (i.e. change in actions 
taken, change in outcome, change in relatedness), an update to the original AE must be 
completed. All reported adverse events must be followed until the adverse event has 
been resolved, is unresolved with no further actions planned, the subject exits the study 
or until study closure, whichever occurs first.  
In the event that a subject is exited from the study prior to study closure, all efforts 
should be made to continue following the subject until all unresolved procedure or 
system related adverse events, as classified by the investigator, are resolved or they are 
unresolved with no further actions planned.  
At the time of study exit, all adverse events with an outcome of “Unresolved, further 
actions or treatment planned” must be reviewed and an update to the original AE must 

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be reported. At a minimum, if there are no changes to the description, relatedness, test 
and procedures or actions taken, the outcome must be updated to reflect “Unresolved at 
time of study closure.” 
11.3 Adverse Events and Device Deficiency Classification 
All reported adverse events and device deficiencies will be reviewed by a Medtronic 
representative. AEs will be classified according to the definitions provided.  
Upon receipt of adverse events 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 adverse event based on the information provided by the investigator.  
Regulatory reporting of AEs and device deficiencies will be completed according to local 
regulatory requirements. Refer to Table 11 for a list of required investigator and 
Medtronic reporting requirements and timeframes. It is the responsibility of the 
investigator to abide by any additional AE reporting requirements stipulated by the IRB 
responsible for oversight of the study. 
For emergency contact regarding a UADE and/or SAE, contact a clinical study 
representative immediately (refer to the study contact list provided in the center’s study 
documents binder/investigator site file or refer to the contact information provided in 
Table 1). 
Adverse Events and Deaths will be classified according to the standard definitions as 
outlined below:  
Table 11: Adverse Event Classification Responsibilities 
What is classified?  Who classifies? Classification Parameters 
Relatedness 
Investigator 
Procedure, Reveal LINQ™ system  
Sponsor 
Procedure, Reveal LINQ™ system 
Seriousness 
Investigator 
SAE 
Sponsor 
SAE, UADE  
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 events and provide a final 
adjudication of the relatedness for all events as well as the complication/observation 
classification for system or procedure related events. Additionally, the CEC will provide 
an adjudication of the death classification for all reported deaths. 
 

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11.4 Adverse Event and Device Deficiency Reporting Requirements 
Regulatory reporting of AEs / Device Deficiencies (DD) will be completed according to 
local regulatory requirements. Refer to Table 12  for a list of required investigator 
reporting requirements and timeframes, and of required Medtronic reporting 
requirements and timeframes. 
The investigator is required to report UADE’s to Medtronic immediately and to the IRB 
per local requirements. Medtronic is also required to report these events to the local 
regulatory authority based on their requirements. It is the responsibility of the 
investigator to abide by any additional AE/DD reporting requirements stipulated by the 
IRB responsible for oversight of the study. 
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.  
Regulatory reporting of AEs/DDs will be completed according to local regulatory 
requirements.  
Table 12: Adverse Event Reporting Requirements 
Unanticipated Adverse Device Effects (UADEs) 
 
Investigator submit to: 
Medtronic 
Submit as soon as possible, but no later than within 10 working days after the 
investigator first learns of the event. (21 CFR 812.150(a)(1)) 
IRB 
Submit as soon as possible, but no later than within 10 working days after the 
investigator first learns of the event. (21 CFR 812.150(a)(1)) 
Sponsor submit to: 
Regulatory authorities 
Submit as soon as possible, but no later than within 10 working days after the 
investigator first learns of the event. (21 CFR 812.150(a)(1)) 
IRB 
Submit as soon as possible, but no later than within 10 working days after the 
investigator first learns of the event. (21 CFR 812.150(a)(1)) 
 
 
All other reportable Adverse Events 
Investigator submit to: 
Medtronic 
Submit in a timely manner after the investigator first learns of the event. 
IRB 
Submit to IRB per local reporting requirement. 
Sponsor submit to: 
Regulatory authorities 
Submit to regulatory authority per local reporting requirement. 
IRB 
Submit to IRB per local reporting requirement. 
Device Deficiencies 
Investigator submit to: 
Medtronic 
Submit in a timely manner after the investigator first learns of the event. 
IRB 
Submit to IRB per local reporting requirement. 
 
11.5 Subject Death 
11.5.1 Death Data Collection 
All subject deaths must be reported by the investigator to Medtronic on a Subject Death 
form as soon as possible after the investigator first learns of the death.  

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In the event of a subject’s death, the implanted system should be explanted and 
returned to Medtronic for analysis whenever possible. Local laws and procedures must 
be followed where applicable. 
System Interrogation Data Recommendations: 
• 
After the subject has died but prior to explant, the device shall be interrogated 
and a full summary interrogation (Interrogate All) performed when possible.   
• 
Make the interrogation file before any programming to prevent overwriting 
information device’s memory and/or distinguishing between events detected 
during versus before the explant procedure 
If the device is not interrogated, an explanation must be entered on the Subject Death 
form.  If any device is returned to Medtronic, internal return product reporting systems 
may be used to gather additional information about the returned device/component. 
A copy of the death certificate, if available and allowed by state/local law, should be sent 
to the Medtronic clinical study team. When a death occurs in a hospital, a copy of the 
death summary report and all relevant hospital records should be sent to the Medtronic 
clinical study team, if available. If an autopsy is conducted, the autopsy report should 
also be sent to the Medtronic clinical study team if available and allowed by state/local 
law. When the death occurs at a remote site, it is the investigative center’s responsibility 
to attempt retrieval of information about the death. Additionally, device disposition 
information should be updated. In summary, the following data will be collected: 
• 
Date of death 
• 
Detailed description of death 
• 
Cause of death  
• 
Relatedness to system and/or procedure 
• 
Device interrogation (if available) 
• 
Device disposition information 
• 
Death summary/hospital records (if available and allowed by state/local law) 
• 
Autopsy report (if available and allowed by state/local law) 
• 
Death certificate (if available and/or allowed by state/local law) 
11.5.2 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. 

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Non-sudden Cardiac Death: All cardiac deaths that are not classified as sudden deaths, 
including all cardiac deaths of hospitalized subjects on inotropic support. 
Non-cardiac Death: A death not classified as a cardiac death. 
Unknown Cardiac Classification: Unknown death classification is intended for use only 
when there is insufficient or inadequate information to classify the death. 
Table 13: Subject Death Classification Responsibilities 
What is classified?  Who classifies? Classification Parameters 
Relatedness 
Investigator 
Procedure, Reveal LINQ™ system 
Death Classification Investigator 
Sudden Cardiac, Non-sudden Cardiac, Non-cardiac, 
Unknown 
The Clinical Events Committee (CEC) will review deaths and provide a final adjudication 
of the primary cause of death, relatedness and cardiac classification. 
Regulatory reporting of Subject Deaths will be completed according to local regulatory 
requirements. Refer to Table 11 for a list of required investigator and sponsor reporting 
requirements and timeframes. 
11.6 Clinical Events Committee (CEC) review 
At regular intervals, an independent Clinical Events Committee (CEC) will conduct a 
medical review of AEs, HCUs and deaths for subjects participating in the study.  
The CEC will consist of a minimum of three (3) non-Medtronic employed physicians that 
are not participating investigators for the study, including a CEC chairperson. At a 
minimum, the CEC will adjudicate all adverse events, deaths, and HCUs as defined in 
section 14.2.5.   
Medtronic personnel may facilitate and participate in a CEC meeting but will be non-
voting members. 
For adverse events and deaths reviewed by the CEC, Medtronic will provide the CEC 
with the Investigator’s description and classification. The CEC is responsible for 
reviewing the Investigator’s assessment and supportive documentation (when available), 
reviewing applicable definitions, and determining final classifications for all adjudication 
parameters. For adverse events, classification includes relatedness and complication or 
observation. Additionally, the CEC will provide an adjudication of the death classification 
for all reported deaths including primary cause of death, relatedness, and cardiac 
classification. 
If the CEC disagrees with the investigator’s classification of the event, the rationale will 
be provided to the investigator. If the investigator agrees with the CEC’s adjudication, 
the case report form documenting the AE will be updated accordingly. 
11.7 Product Complaint Reporting 
In geographies where devices are market-released, product complaint reporting is 
applicable. This includes when an AE is related to a market-released device during the 
study.  The reporting of product complaints is not part of the clinical study and should be 

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done in addition to the Adverse Event reporting requirements.  Refer to local regulations 
for reporting requirements. 
Product Complaint: Any written, electronic or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, safety, effectiveness or 
performance of a medical device that has been placed on the market. 
It is the responsibility of the investigator to report all product complaint(s) associated with 
a medical device distributed by Medtronic, regardless whether they are related to 
intended use, misuse or abuse of the product. Reporting must be done immediately and 
via the regular channels for market-released products. 
Medtronic will notify the regulatory authorities, as applicable for the following incidents 
immediately upon learning of them: 
• 
Any malfunction or deterioration in the characteristics and/or performance of a 
device, as well as any inadequacy in the labeling or instructions for use which led 
or might have led to the death or serious deterioration in the state of health of a 
patient, user, or other person. 
• 
Any technical or medical reason resulting in withdrawal of a device from the 
market by the manufacturer. 
• 
A serious deterioration in the state of heath includes: 
o Life-threatening illness or injury, or 
o Permanent impairment of a body structure function or a body function, or 
o In-patient or prolonged hospitalization, or 
o Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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12 RISK ANALYSIS 
Medtronic follows rigorous Quality Assurance and Control procedures throughout the 
research development process and for the duration of the clinical study. The risk 
analysis process for the LINQ™ Heart Failure (HF) study is being performed in 
accordance with ISO 14971, and ensures that the level of residual risk is reduced to as 
low as possible prior to starting the clinical study.  
There are potential risks and side effects associated with a Reveal LINQ™ device 
implant and explant procedures:  
• 
Allergenic reaction or device rejection phenomena including local tissue reaction 
• 
Excessive device migration (internal pocket device movement as well as device  
externalization)  
• 
Pocket infection 
• 
Erosion through the skin 
• 
Tissue / vascular trauma 
Possible additional risks for participating in this study include the following (although 
others are possible): 
• 
The Reveal LINQ™ device with the LINQ™ HF RAMware download is 
investigational and may be no more effective or less effective than a 
commercially available Reveal LINQ™ device system. 
• 
 
  
• 
 
 
 
 
 
• 
There may be undesired device interactions with the LINQ™ HF investigational 
RAMware, potentially resulting in loss of or inaccurate Reveal LINQ™ data, 
and/or premature explant. Once the LINQ™ HF investigational RAMware feature 
set is executed, periodic data integrity checks are in place to ensure correct 
functionality. 
• 
The Reveal LINQ™ device with the LINQ™ HF investigational RAMware 
download may present data that are different than anticipated due to unknown 
circumstances or medical conditions.  
• 
There may be other discomforts and risks related to the Reveal LINQ™ device 
with LINQ™ HF investigational RAMware download and/or this study that are not 
foreseen at this time. 

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12.1 Risk Minimization 
The potential risks associated with the LINQ™ HF investigational RAMware were 
identified, assessed, evaluated and effectively controlled. Any potential risks associated 
with this study are further minimized by selecting qualified investigators and training 
study personnel on the Clinical Investigation Plan. 
In addition, investigators will be actively involved in the implantation and regular follow-
up of the subjects implanted with the Reveal LINQ™ with investigational RAMware 
systems. At each office follow-up visit required per protocol (Table 6: Data collection and 
study procedure requirements at subject visits), the LINQ™ device will be interrogated, 
device data collected to verify appropriate device function and patient’s health assessed 
for any adverse events. 
Medtronic is further minimizing the possibility of risks by: performing required laboratory 
and pre-clinical testing prior to the clinical study, implementing quality control measures 
into production processes, providing guidelines for subject selection and evaluation, and 
providing adequate instructions and labeling.  
Table 14: Potential Risks and Risk Minimization 
Potential Risk  
Minimization 
ICM Pocket Infection from implant/ 
explant procedure or over duration 
of implant 
• 
Industry standard sterilization and procedural 
      processes will be followed to minimize the risk of  
      infection 
• 
Wound check following implant, per site’s practice 
Allergenic reaction or ICM Rejection 
following implant procedure 
• 
Assessment of subjects to ensure no allergenic or 
rejection reaction to materials used in incision/insertion 
tools, Reveal LINQ™ ICM exterior or incision closure 
method 
• 
Wound check following implant, per site’s practice 
• 
Close monitoring with follow-up appointments 
• 
Investigator discretion to remove ICM and report study 
deviation 
• 
Use of biocompatible materials in the Incision/ Insertion 
Tools and Reveal LINQ™ ICM exterior patient-
contacting surfaces 
Excessive ICM Migration following 
implant procedure (internal device 
movement and externalization) 
• 
Wound check following implant, per site’s practice 
• 
Training and Information for User on the Reveal 
LINQ™ implant technique and incision closure 
techniques 
• 
Use of the implant tools to create small incision and 
tight pocket 
• 
Reveal LINQ™ ICM design includes anti-migration 
features on the header 
• 
Investigator discretion to remove if deemed medically 
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Potential Risk 
Minimization 
Blunt Tissue Injury/Tissue or 
Vascular Trauma from implant/ 
explant procedure 
•
Insertion Tool has a stop position that prevents
insertion of the probe beyond the distance required for
prototype implant.
•
Training on the correct use of implant tools
•
Selection of experienced investigators
Pain, Scarring from implant/explant 
procedure 
•
Use of incision tool will produce the smallest incision
possible for implant
•
Small device size minimizes the invasiveness of the
implant and explant procedures
Undesired device interactions with 
the investigational RAMware 
•
Device interactions analysis to ensure there are no
undesired interactions between the LINQ™ HF
investigational RAMware and the Reveal LINQ™
device firmware.
•
LINQ™ HF investigational RAMware is designed to be
automatically removed by the ROM code during POR
processing
Premature/Unexpected ICM explant •
Electromagnetic interference 
•
Design consideration and precautions in place for the
Reveal LINQ™ system remain effective to address EMI
risks
 
 
 
Missing/Misleading information 
causing inappropriate medical 
intervention 
•
Data integrity checks have been implemented
•
Validation testing of the system set-up will be
performed
Improper LINQ™ HF investigational 
RAMware access and activation  
•
Access code and preconditions are in place for
appropriate activation
•
Data integrity checks have been implemented
12.2 Potential Benefits 
The Reveal LINQ™ HF study may offer no direct personal benefit to individual subjects. 
Subjects may benefit from continuous arrhythmia monitoring with the Reveal ICM, as 
this monitoring could result in diagnosis of Atrial Fibrillation (or other arrhythmias) and 
comprehensive evaluation of symptoms on an earlier and more conclusive basis than 
what would be possible without an implantable cardiac monitor. Subjects may also 
benefit from being evaluated more frequently in the office according to the study visit 
schedule. 

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The information gained from this study could result in the improved management of 
other patients receiving a Reveal LINQ™ device in the future. Additionally, information 
collected from this study may assist in the design of new product(s)/therapy(ies) and/or 
instructions for use. 
12.3 Risk-to-Benefit Analysis 
Since the differences between the Reveal LINQ™ market-released device and the 
Reveal LINQ™ device with the LINQ™ HF investigational RAMware download are 
minimal, both devices are used in accordance with the Reveal LINQ™ implant manual 
and/or user manual, as applicable. The risks associated with the device are similar as 
would be the case if the subject received a Reveal LINQ™ device outside the study 
context. The risks introduced by the LINQ™ HF investigational RAMware are being 
evaluated and risk control measures being implemented to reduce the risk to as low as 
possible to minimize patient harm.  
The study requirements for careful physician selection and training, and in-office visits 
carry potential benefits that might not be present if the subject was not enrolled in the 
study.  Hence, for individual subjects, participation in the study may have greater benefit 
than risk. Moreover, the value of the knowledge to be gained by conducting this clinical 
study could help in the diagnosis of future patients.  Lastly, the prospective benefit to 
LINQ™ HF subjects of having Reveal LINQ™ cardiac monitoring, with the potential to 
diagnose life-threatening arrhythmias, may provide the patient significant clinical benefit. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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13 PLANNED STUDY CLOSURE, EARLY 
TERMINATIONOF STUDY OR STUDY SUSPENSION 
13.1 Planned Study Closure 
Study Closure is a process initiated by distribution of a study closure letter. Study 
closure is defined as closure of a clinical study that occurs when Medtronic and/or 
regulatory requirements have been satisfied per the Clinical Investigation Plan and/or by 
a decision by Medtronic or regulatory authority, whichever occurs first. The study closure 
process is complete upon distribution of the Final Report or after final payments, 
whichever occurs last. Ongoing IRB oversight is required until the overall study closure 
process is complete. Refer to section 8.16 for additional information regarding study exit 
procedures. 
13.2 Early Termination or Suspension 
Early Termination of the Study is the closure of a clinical study that occurs prior to 
meeting defined endpoints. This is possible for the whole study or a single center. Study 
Suspension is a temporary postponement of study activities related to enrollment and 
distribution of the product. This is possible for the whole study or a single center. 
13.2.1 Study-wide Termination or Suspension 
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 
13.2.2 Investigator/center Termination or Suspension 
Possible reasons for clinical investigator or center termination or suspension include but 
are not limited to: 
• 
Failure to obtain initial IRB approval or annual renewal of the study 
• 
Persistent non-compliance to the clinical investigation (e.g. failure to adhere to 
inclusion/exclusion criteria, failure to follow subjects per scheduled follow-ups)  
• 
Lack of enrollment 
• 
Noncompliance to regulations and the terms of the Clinical Trial Agreement (e.g. 
failure to submit data in a timely manner, failure to follow-up on data queries and 
monitoring findings in a timely manner, etc.)  
• 
IRB suspension of the center 
• 
Fraud or fraudulent misconduct is discovered (as defined by local law and 
regulations)  
• 
Investigator request (e.g. no longer able to support the study)  

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13.3 Procedures for Termination or Suspension 
13.3.1 Medtronic-initiated and Regulatory Authority-initiated 
• 
Medtronic will promptly inform the clinical investigators of the termination or 
suspension and the reasons and inform the regulatory authority(ies) where 
required 
• 
In the case of study termination or suspension for reasons other than a 
temporary IRB approval lapse, the investigator will promptly inform the IRB.  
• 
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 
13.3.2 Investigator-initiated 
• 
The investigator will inform Medtronic and provide a detailed written explanation 
of the termination or suspension 
• 
The investigator will promptly inform the institution (where required per regulatory 
requirements)  
• 
The investigator will promptly inform the IRB 
• 
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 
13.3.3 IRB-initiated 
• 
The investigator will inform Medtronic and provide a detailed written explanation 
of the termination or suspension within 5 business days 
• 
Subject enrollment must stop until the suspension is lifted 
• 
Subjects already enrolled should continue to be followed in accordance with IRB 
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, or legally-authorized designees 
and/or the personal physician of the subjects, with the rationale for the study 
termination or suspension.  

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14 STATISTICAL METHODS AND DATA ANALYSIS 
14.1 General Considerations 
Medtronic statisticians or designee will conduct all statistical analyses. The study is an 
event driven study with no formal statistical hypothesis planned. A separate Statistical 
Analysis Plan (SAP) will be developed and include a comprehensive description of the 
statistical methods and reports to be included in the final study report. Any change to the 
data analysis methods described in the protocol will require an amendment only if it 
changes a principal feature of the protocol. Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be 
described in the clinical study report.  
14.2 Primary Objective 
The primary objective is to characterize Reveal LINQ™ derived data from patients with 
heart failure by assessing the relationship between changes in LINQ™ derived data and 
other physiologic parameters with subsequent ADHF events. 
14.2.1 Endpoint Definitions 
The ADHF events as adjudicated by the CEC that will be used in the primary analysis 
are those that are ≥30 days following implant in order to ensure sufficient LINQ™ 
derived data prior to the event onset are available. A second ADHF event within a 
subject may be used if the second ADHF event is >90 days following the first event.  In 
the event a subject has > 2 qualifying ADHF events, only the first two will be used in the 
primary analysis. Additional analyses including all qualifying ADHF events may be 
conducted. 
14.2.2 Analysis Methods 
Physiologic data (including heart rate, bioimpedance, activity, blood pressure and 
weight), as well as blood samples (including serum BUN, creatinine, NT-proBNP, 
hemoglobin, hematocrit, troponin, eGFR and electrolytes), will be collected from subjects 
with acute decompensated heart failure. 
 
 
 Data will be collected from enrollment 
up to 3 years post-insertion. If a subject exits the study prematurely, data captured prior 
to exit will be included in the analysis. All data collected will be included in the analysis. 
Descriptive statistics (e.g. means, standard deviations, proportions) will be used to 
summarize the physiological and derived data recorded. Analyses will be conducted to 
assess changes in the physiologic and LINQ™ derived data in association with HF 
events. 
14.2.3 Determination of Patients/Data for Analysis 
All subjects with a successful insertion will be used in the analysis. 
14.2.4 Sample Size 
There are no sample size requirements as this is an observational study. The sample 
size was selected in order that data can be derived from an estimated 40 subjects with a 
why is the descriptive statistics redacted? (BN)

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HF event within 12 months. This provides a conservative estimate of the required 
number of subjects. The CHAMPION study provides a 12 month KM estimate of HF 
hospitalization of 30% for Class III subjects. 17 To be conservative, it is assumed 25% of 
enrolled subjects will have at least one HF event within 12 months. If the estimate is 
used as a binomial proportion, a sample size of 300 subjects would accrue ≥40 subjects 
with event within 12 months with > 99% probability. If the proportion of subjects with HF 
event is lower than 25%, the probability of at least 40 subjects with at least one HF event 
is >91% if the underlying proportion of subjects with event is ≥16%. The projected 
enrollment number of 300 may be readjusted if the frequency of HF events is higher or 
lower than anticipated. 
14.2.5 Heart Failure (HF) Event Definition 
A heart failure event is defined as any cardiovascular-related (including hypervolemia) 
Health Care Utilizations (HCUs) for any one of the following events. 
•
Admission with primary diagnosis of HF
•
Intravenous HF therapy (e.g. IV diuretics/vasodilators) or ultrafiltration at any one
of the following settings:
o
Admission with secondary/tertiary diagnosis of HF
o
Emergency Department
o
Ambulance
o
Observation Unit
o
Urgent Care
o
HF/Cardiology Clinic
14.3 Interim Analysis 
No interim analysis is planned in this study. Since there is no interim analysis planned, 
there are no criteria for early termination based on statistical evidence. 
14.4 Missing Data 
Missing data will not be imputed. In order to be included in the primary analysis, an 
ADHF event must have complete LINQ™ data downloads prior to the event. If device 
data is missing, the event will not be included in the primary analysis. 
14.5  Subgroup Analysis 
No subgroup analysis is planned in this study. 

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15 DATA AND QUALITY MANAGEMENT 
Data will be collected using an electronic data management system for clinical studies.  
CRF data will be stored in a secure, password-protected database which will be backed 
up nightly.  Data will be reviewed using programmed and manual data checks.  Data 
queries will be made available to centers for resolution.  Study management reports may 
be generated to monitor data quality and study progress.  At the end of the study, the 
data will be frozen and will be retained indefinitely by Medtronic. 
All records and other information about subjects participating in this study will be treated 
as confidential. Data will be transferred and processed by Medtronic or a third party 
designated by Medtronic in a key coded form, unless it’s impossible to make it 
anonymous, for instance, where the subject’s name cannot be removed from the data 
carrier. 
Procedures in the CIP require source documentation.  Source documentation will be 
maintained at the site. Source documents, which may include worksheets, patient 
medical records, programmer printouts, and interrogation files, must be created and 
maintained by the study center.  
The data reported on the eCRFs shall be derived from source documents and be 
consistent with these source documents, and any discrepancies shall be explained in 
writing.  
Device data from transmissions will be uploaded to secure servers.  Media/USB data 
collected at office visits will be sent to Medtronic.  Upon receipt, device data will be 
maintained with databases and retrieved for analysis and reporting. 
The sponsor or a regulatory authority may audit or inspect the study center to evaluate 
the conduct of the study. The clinical investigator(s)/institution(s) shall allow study 
related monitoring, audits, IRB review and regulatory inspection by providing direct 
access to source data/documents. 
 
 

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16 WARRANTY/INSURANCE INFORMATION 
16.1 Warranty 
Warranty information is provided in the product packaging for the LINQ™ ICM.  
Additional copies are available upon request. 
 
 

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17 MONITORING 
It is the responsibility of Medtronic to ensure proper monitoring of this clinical study. 
Trained Medtronic personnel or delegates appointed by Medtronic may perform study 
monitoring at the study center or via remote monitoring in order to ensure that the study 
is conducted in accordance with the CIP, the Clinical Trial Agreement, and applicable 
regulatory and local requirements. Medtronic, or delegates, must therefore be allowed 
access to the subjects’ case histories (clinic and hospital records, and other source 
data/documentation) upon request as per the Patient Informed Consent Form, Research 
Authorization (where applicable) and Clinical Trial Agreement. The principal investigator 
should also be available during monitoring visits.   
17.1 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. Regulatory documents may be reviewed at each study center. Monitoring 
for the study, including site qualification visits, site initiation visits, interim monitoring 
visits, and closeout visits will be done in accordance to the Reveal LINQ™ HF 
monitoring plan. 
Monitoring visits may be conducted periodically to assess site study progress, the 
investigator’s adherence to the CIP, regulatory compliance including but not limited to 
IRB approval and review of the study, maintenance of records and reports, and review of 
source documents against subject eCRFs. Monitors review site regulatory and study 
compliance by identifying findings of non-compliance and communicating those findings 
along with recommendations for preventative / corrective actions to site personnel.  
Monitors may work with study personnel to determine appropriate corrective action 
recommendations and to identify trends within the study or at a particular center.  
17.2 Access to the Site and Study Materials 
The investigator will permit study related monitoring, audits, IRB review and regulatory 
inspections by providing direct access to source data and source documents.  
 
 
 
 
 
 
 
 

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18 REQUIRED RECORDS AND REPORTS 
18.1 Investigator Records 
The investigator is responsible for the preparation and retention of the records cited 
below. All of the below records, with the exception of case history records and case 
report forms, should be kept in the Investigator Site File (i.e., the study binder provided 
to the investigator) or Subject Study Binder. CRFs must be maintained and signed 
electronically within the electronic data capture system during the study. The following 
records are subject to inspection and must be retained for a period of two years (or 
longer as local law or hospital administration requires) after the date on which the 
investigation is terminated. 
• 
All correspondence between the IRB, sponsor, monitor, FDA, regulatory authority 
and the investigator that pertains to the investigation, including required reports.  
• 
Subject’s case history records, including:  
o Signed and dated Patient Informed Consent Form 
o Observations of adverse events/adverse device effects/device deficiencies 
o Medical history 
o LINQ™ Insertion and follow-up data  
o Documentation of the dates and rationale for any deviation from the protocol 
• 
List of investigation sites 
• 
Financial disclosure  
• 
Normal value(s)/range(s) for clinical laboratory tests  
• 
Lab certificate (if applicable) 
• 
Investigational product traceability records  
• 
Non implantable product traceability records (if applicable)  
• 
All approved versions of the CIP, PIC and Report of Prior Investigation Summary 
• 
Signed and dated Clinical Trial Agreement 
• 
Current curriculum vitae principal investigators  
• 
Documentation of delegated tasks 
• 
IRB approval documentation. Written information that the investigator or other 
study staff, when member of the IRB, did not participate in the approval process. 
Approval documentation must include the IRB composition, where required per 
local law 
• 
Regulatory authority notification, correspondence and approval, where required 
per local law 
• 
Study training records for site staff 
• 
Any other records that FDA and local regulatory agencies require to be 
maintained (e.g financial disclosure) 
• 
Final Study Report including the statistical analysis 
 
 

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18.2 Investigator Reports 
The investigator is responsible for the preparation (review and signature) and 
submission to the sponsor of all case report forms, adverse events and adverse device 
effects (reported per the country-specific collection requirements), device deficiencies, 
deaths, and any deviations from the clinical investigation plan.  If any action is taken by 
an IRB 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 section 11.The investigator 
shall prepare and submit in a complete, accurate and timely manner the reports listed in 
this section. 
If any action is taken by an IRB with respect to this clinical study, copies of all pertinent 
documentation must be forwarded to Medtronic in a timely manner.  
Table 15: Investigator Reports per Medtronic Requirements 
Report  
Submit to 
Description/Constraints 
Withdrawal of IRB 
approval 
Sponsor and 
Relevant 
Authorities, if 
applicable 
The investigator must report a withdrawal of approval 
by the reviewing IRB of the investigator’s part of the 
investigation within 5 working days. 
Study deviations  
Sponsor and 
IRB 
Notice of deviations from the CIP to protect the life or 
physical wellbeing of a subject in an emergency shall 
be given as soon as possible, but no later than 5 
working days after the emergency occurred.  Except 
in such emergency, prior approval is required for 
changes in the plan or deviations.  If the deviation 
may affect the scientific soundness of the plan or the 
rights, safety and welfare of the subjects, the 
deviation must be approved by Medtronic, the IRB, 
and the FDA/applicable regulatory authorities.  If the 
deviation does not affect these issues then only 
Medtronic must approve it.  (21 CFR 812.150(a)(4)) 
Withdrawal of IRB 
approval (either 
suspension or 
termination) 
Sponsor 
The investigator must report a withdrawal of approval 
by the reviewing IRB of the investigator’s part of the 
investigation within 5 working days.  (21 CFR 
812.150(a)(2)) 
Progress report  
Sponsor and 
IRB 
The investigator must submit this report to the 
sponsor and IRB at regular intervals, but in no event 
less than yearly. (21 CFR 812.150 (a)(3)).   
Failure to obtain 
informed consent 
prior to 
investigational 
device use 
Sponsor and 
IRBs 
If an investigator uses a device without obtaining 
informed consent, the investigator shall report such 
use within 5 working days after device use.  (21 CFR 
812.150(a)(5)) 
Final report 
Sponsor and 
IRBs 
 
This report must be submitted within 3 months of 
study completion or termination of the investigation or 
the investigator’s part of the investigation.  (21 CFR 
812.150(a)(6)) 

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18.3 Sponsor Records 
Medtronic shall maintain the following accurate, complete, and current records which 
include, but are not limited to: 
• 
All correspondence which pertains to the investigation 
• 
Signed Investigator Trial Agreements, financial disclosure and curriculum vitae of 
principal investigator and delegated task list 
• 
All approved informed consent templates, and other information provided to the 
subjects and advertisements, including translations 
• 
Copies of all IRB approval letters and relevant IRB correspondence and IRB 
voting list/roster/letter of assurance, if applicable 
• 
Names of the institutions in which the clinical study will be conducted 
• 
Regulatory authorities correspondence, notification and approval as required by 
national legislation 
• 
Names/contact addresses of monitors 
• 
Statistical analyses and underlying supporting data 
• 
Final report of the clinical study 
• 
The Clinical Investigation Plan,  Report of Prior Investigations summary and 
study related reports, and revisions 
• 
Study training records for site personnel and Medtronic personnel involved in the 
study 
• 
Any other records that local regulatory agencies require to be maintained 
• 
Investigational product traceability records  
• 
Non-implantable product traceability records  
18.4 Sponsor Reports 
Medtronic shall prepare and submit the following complete, accurate, and timely reports 
listed in the table below. In addition to the reports listed below, Medtronic shall, upon 
request of reviewing IRB and/or regulatory agency provide accurate, complete and 
current information about any aspect of the investigation. Safety data Medtronic 
reporting requirements are listed in Table 11 of the Adverse Event section. 
 
 
 
 
 
 
 
 

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Table 16: Sponsor Reports  
Report  
Submit to 
Description/Constraints 
Withdrawal of IRB 
approval 
Investigators, 
IRB 
Notification within five working days.  (21 CFR 
812.150(b)(2))   
Progress Reports IRB  
Progress reports will be submitted at least annually.  
(21 CFR 812.150(b)(5), 812.36(f)   
Recall and device 
disposition 
Investigators, 
IRB  
Notification within 30 working days and will include 
the reasons for any request that an investigator 
return, repair, or otherwise dispose of any devices.  
(21 CFR 812.150(b)(6)) 
Final report 
Investigators, 
IRB 
A final report will be submitted to investigators and 
IRBs within six months after completion or 
termination of this study.  (21 CFR 812.150(b)(7)) 
Study Deviation  
Investigators 
Ensure that all deviations from the Clinical 
Investigation Plan are reviewed with the appropriate 
clinical investigator(s), are reported on the case 
report forms and the final report of the clinical 
investigation.  
Site specific study deviations will be submitted to 
investigators periodically.   
Significant risk 
device 
determination 
FDA 
If an IRB determines that the device is a significant 
risk device, the sponsor shall submit to FDA a report 
of the IRB’s determination within 5 working days after 
sponsor learns of the determination. (21CFR 
812.150(b)(9)) 
 
Medtronic records and reports will be stored in a password-protected document 
management system.   
The sponsor and principal investigator shall maintain the clinical investigation documents 
as required by the applicable regulatory requirement(s). They shall take measures to 
prevent accidental or premature destruction of these documents. The principal 
investigator or sponsor may transfer custody of records to another person/party and 
document the transfer at the investigation site or at the sponsor's facility. 
 

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Appendix A: Data Collection Elements (Case Report 
Forms) 
A copy of the Case Report Forms for the Reveal LINQ™ Heart Failure (HF) Study is 
available under separate cover.  Final CRFs 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: Preliminary Publication Plan 
Publications from the Reveal LINQ™ Heart Failure (HF) Study will be handled according 
to Medtronic’s Standard Operating Procedures and as indicated in the Clinical Trial 
Agreement. 
Publication Committee 
Medtronic may form the Reveal LINQ™ Heart Failure (HF) Publication Committee from 
study investigators.  Medtronic personnel may serve as members of the committee.  This 
committee will manage study publications with the goal of publishing findings from the 
data.  The Publication Committee will develop the final Publication Plan as a separate 
document.   
The Publication Committee’s role is to: 1) manage elements addressed in the publication 
plan as outlined in this appendix, 2) develop the final Publication Plan under separate 
cover, 3) execute the Publication Plan, 4) oversee the publication of primary and 
ancillary study results, 5) review and prioritize publication proposals, 6) provide input on 
publication content, and 7) determine authorship.  In addition, the committee will apply 
and reinforce the authorship guidelines set forth in the Publication Plan.   
Membership in the Publication Committee does not guarantee authorship.  The 
committee will meet as needed. 
Management of Primary and Ancillary Publications 
The Publication Committee reviews, prioritizes, and manages all publications including 
primary and ancillary publications.  Primary publications are those that address analyses 
of the primary objective as specified in the Clinical Investigation Plan.  
An ancillary publication is any publication that does not address the primary study 
objective identified in the Clinical Investigation Plan.  They include publications proposed 
and developed by the Publication Committee, other Medtronic departments or entities, 
clinicians participating in this clinical study, and clinicians not participating in this clinical 
study.  The committee will work with Medtronic to ensure that requests do not present 
conflicts with the primary results, other proposals, are not duplicative, and to determine 
which ancillary publication proposals, if any, will be supported.   
The committee may decide that no publications, including abstracts, will be published 
prior to the end of the study or with individual center data.  Requests for publications on 
study objectives utilizing subset data (e.g., regional) will be evaluated for scientific 
validity and the ability of Medtronic to provide resources.   
Criteria for Determining Authorship 
Publications will adhere to authorship criteria defined by the International Committee of 
Medical Journal Editors (ICMJE, Uniform requirements for manuscripts submitted to 
biomedical journals, www.icmje.org).  Individual authorship criteria defined by the target 
journal or conference will be followed when it differs from ICMJE criteria. 
Authors, including Medtronic personnel, must at a minimum meet all of the conditions 
below: 

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• 
Substantial contributions to the conception or design of the work; or the 
acquisition, analysis, or interpretation of data for the work; AND 
• 
Drafting the work or revising it critically for important intellectual content; AND 
• 
Final approval of the version to be published; AND 
• 
Agreement to be accountable for all aspects of the work in ensuring that 
questions related to the accuracy or integrity of any part of the work are 
appropriately investigated and resolved. 
Decisions regarding authorship and contributor-ship will be made by the committee 
according to a priori ranking system. The selected authors will be responsible for drafting 
the publication. All selected authors must fulfill the authorship conditions stated above to 
be listed as authors 
All investigators not listed as co-authors will be acknowledged as the “Medtronic Reveal 
LINQ™ Heart Failure (HF) Clinical Study Investigators” and will be individually listed 
according to the guidelines of the applicable scientific journal when possible and 
affiliation. Any other contributors will be acknowledged by name with their specific 
contribution indicated. 
Transparency 
Transparency of study results will be maintained by the following means: 
• 
a final report, describing the results of all objectives and analysis, will be 
distributed to all investigators and IRBs. 
• 
registering and posting the study results on ClinicalTrials.gov based on the 
posting rules stipulated  
• 
submitting for publication the primary study results after the study ends  
• 
disclosing conflicts of interest (e.g., financial) of the co-authors of publications 
according to the policies set forth by the corresponding journals and conferences  
• 
making an individual centers study data accessible to the corresponding 
investigator after the completion of the study, if requested 
 
 

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Appendix C: LINQ™ HF Study Procedure Handbook 
A LINQ™ HF Study Procedure handbook that will provide instructions on how to use the 
DR220 Holter during the 6 Minute Hall Walk test and 
 
 
 
 
 
 
 
 

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Appendix D: Patient Informed Consent Form Template 
Patient Informed Consent Form will be provided under separate cover. 
 

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Appendix E: Participating Investigators and Institutions 
A complete list of participating investigators and institutions where study activities will be 
conducted will be provided under separate cover. 
This information will be updated throughout the course of the study. The updated list will 
be maintained at Medtronic and will be available upon request. 
 
 

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Appendix F: IRB Committee List 
A complete list of participating IRBs and the Chairperson(s) will be provided under 
separate cover.  
This information will be updated throughout the course of the study. The updated list will 
be maintained at Medtronic and will be available upon request. 
 
 
 
 
 

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Appendix G: Labeling 
Labeling for the LINQ™ HF investigational RAMware will be provided under separate 
cover. Labeling for all other market approved system components can be found with 
each package insert. 
In addition, the subject may receive an Instructions manual on how to perform the 
manual device transmission. This will be provided under separate cover, if applicable. 
 
 
 
 

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Appendix H: Bibliography 
A complete bibliography and summary of relevant literature, summary and results of 
preclinical testing and summary and results of previous clinical investigational is 
provided in the Report of Prior Investigation (RPIS). 
[1] Jencks SF, Williams MV, Coleman EA (2009) Rehospitalizations among Subjects in 
the Medicare Fee-for-Service Program. New England Journal of Medicine 360(14): 
1418-1428. 
[2] Ahmed A, Allman R, Fonarow G, Love TE, Zannad F, Dell’Italia LJ, White M, 
Gheorghiade M. (2008) Incident Heart Failure Hospitalization and Subsequent Mortality 
in Chronic Heart Failure: A Propensity-Matched Study. Journal of Cardiac Failure 1 4(3): 
211-218. 
[3] Solomon SD, Dobson K, Pocock S, Skali H, McMurray JJV, Granger CB, Yusuf S, 
Swedberg K, Young JB, Michelson EL, Pfeffer MA and for the Candesartan in Heart 
failure: Assessment of Reduction in Mortality and mortality (CHARM) Investigators 
(2007) Influence of Nonfatal Hospitalization for Heart Failure on Subsequent Mortality in 
Subjects with Chronic Heart Failure. Circulation 116(13):1482-1487. 
[4] Fonarow GC, Stough WG, Abraham WT, Albert NM, Gheorghiade M, Greenberg BH, 
O’Connor CM, Sun JL, Yancy CW, Young JB (2007) Characteristics, Treatments, and 
Outcomes of Subjects with Preserved Systolic Function Hospitalized for Heart Failure: A 
Report from the OPTIMIZE-HF Registry. Journal of the American College of Cardiology 
50(8): 768-777. 
[5] Whellan, David, et. al. Combined Heart Failure Device Diagnostics Identify Patients 
at Higher Risk of Subsequent Heart Failure Hospitalizations. Journal of American 
College of Cardiology, Vol. 55, No. 17, 2010. 
[6] Cowie, Martin, et. al. Development and validation of an integrated algorithm derived 
from parameters monitored in implantable devices for identifying patients at risk for heart 
failure hospitalization in an ambulatory setting. European Heart Journal, 2013. 
 
[7] Auricchio, Angelo, et.al. Assessment of a novel device-based diagnostic algorithm to 
monitor patient status in moderate-to-severe heart failure: rationale and design of the 
CLEPSYDRA Study. European Journal of Heart Failure, 2010. 
 
[8] Boehmer, John, et. al. Rationale and Design of the Multisensor Chronic Evaluations 
in Ambulatory Heart Failure Patients (MultiSENSE) Study. Cardiac Rhythm Management, 
6:2137-2143, 2015. 
 
[9] Abraham, William, et. al. Intrathoracic Impedance vs Daily Weight Monitoring for 
Predicting Worsening Heart Failure Events: Results of the Fluid Accumulation Status 
Trial (FAST). Congestive Heart Failure, Vol 17, Issue 2, March/April 2011. 
 
[10] Adamson, et. al. Continuous Autonomic Assessment in patients with symptomatic 
heart failure: Prognostic Value of Heart Rate variability measured by an Implantable 
Cardiac Resynchronization Device, Circulation 110:2389-2394, 2004. 
 

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[11] Goetze, Stephan, et. al. Ambulatory respiratory rate trends identify patients at higher 
risk of worsening heart failure in implantable cardioverter defibrillator and biventricular 
device recipients: a novel ambulatory parameter to optimize heart failure management. J 
Inter Card Electrophysiol, 43:21-29, 2015. 
 
[12] Katra, Rodolphe, Niranjan Chakravarthy, Remote At-Home Detection and 
Monitoring of Functional Chronotropic Incompetence in Heart Failure Patients. J of 
Cardiovasc Trans. Res. 4:14-20, 2011. 
 
[13] Yu CM, Wang L, Chau E, et al.  Intrathoracic impedance monitoring in patients with 
heart failure: correlation with fluid status and feasibility of early warning preceding 
hospitalization.  Circulation 2005;112(6):841-8. 
 
[14] Roy-Chaudhury, P, Williamson, DE, Tumlin, JA, Kher, VK, Prakash, K, Charytan DM, 
Tiwari, SC, Pokhariyal, S, Podoll, AS.  “Monitoring in Dialysis (MiD) Study: Exploring the 
Timeline and Etiology of Increased Arrhythmias in Hemodialysis (HD) Patients.”  J Am 
Soc Nephrol; 2015: Late Breaking Clinical Trial Poster (SA-PO1112). 
 
[15] Ekman, I., et. al. Symptoms in patients with heart failure are prognostic predictors: 
insights from COMET. Journal of Cardiac Failure. 11, 288–292, 2005. 
 
[16] Silva, L., et. al. Persistent orthopnea and the prognosis of patients in the heart 
failure clinic. Congestive Heart Failure, 10, 177–180, 2004. 
 
[17] Philip B. Adamson, William T. Abraham, Robert C. Bourge, Maria Rosa Costanzo, 
Ayesha Hasan, Chethan Yadav, John Henderson, Pam Cowart, and Lynne Warner 
Stevenson. Wireless Pulmonary Artery Pressure Monitoring Guides Management to 
Reduce Decompensation in Heart Failure With Preserved Ejection Fraction. Circ Heart 
Fail. 2014;7:935-944. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Appendix I: Pre-clinical Testing 
A summary and results of pre-clinical testing is provided in the LINQ™ HF Report of 
Prior Investigations Summary (RPIS). 
 

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Appendix J: Previous Clinical Investigations 
A summary and results from previous clinical investigations related to the LINQ™ HF 
study or devices with similar features is provided in the Report of Prior Investigations 
Summary (RPIS).  
 
 

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Appendix K: Committees 
The Reveal LINQ™ Heart Failure (HF) study will utilize a Clinical Events Committee 
(CEC) for the assessment of Adverse Events, Healthcare Utilizations and Deaths.  
The Reveal LINQ™ Heart Failure (HF) study may utilize a Publication Committee aiming 
to manage study publications. 
A Data Monitoring Committee (DMC) is not needed for this study.  This decision was 
made based on the following criteria: fast enrollment in this trial (approximately 18 
months) making a DMC impractical, and it is felt there are no additional benefits of a 
DMC reviewing the data in addition to the Clinical Events Committee (CEC). 
The updated member lists will be maintained at Medtronic and will be made available 
upon request. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Appendix L: Summary of Changes 
Version 
Summary of Changes 
Author 
1.0 
Initial Release 
Jennifer Seamans, 
Principal Clinical 
Research Specialist 
2.0 
Section 1.2: Updated sponsor contact 
information in Table 1 to reflect change in 
worldwide study leader. 
Aimee Laechelt, 
Senior Clinical 
Research Specialist 
Section 1.4: Added Steering Committee 
membership and contact information since 
committee is now established. 
Sections 2 and 5: Updated Tables 4 and 6 to 
allow for subsequent versions of the 
investigational RAMware to be utilized since an 
updated version is expected to be released, with 
clarifying language beneath table.  
Sections 2 and 7.3: Updated inclusion criteria to 
clarify window allowed for the NYHA III criterion.  
Sections 2 and 7.3: Updated BNP/NTpro-BNP 
inclusion criterion to clarify categorization for 
patients with EF=50, to clarify that the 3-month 
window applies to the BNP/NTpro-BNP 
measurement, and to specify units for 
BNP/NTpro-BNP.  
Section 8.11: Updated to clarify recommended 
frequency for phone calls to subjects to ensure 
complete and timely reporting of HCUs, and to 
clarify timing of follow-up windows and how they 
will be provided to sites.  
Section 8.12: Updated to clarify that a deviation 
form will not be required for a missed monthly 
transmission if a device interrogation performed 
within the window is provided to Medtronic, since 
the device interrogation would capture all of the 
required data.  
Section 8.14: Clarified scope of types of HCUs to 
be reported, and reformatted for further clarity.  
Section 9: Removed statement that study 
components can only be ordered by Medtronic, 
since sites can place an order directly to 
Medtronic (which is acceptable since Medtronic 
manages distribution of product).  
Section 9: Added clarification that only the 
patient assistants kept at the site need to be 
tracked since they need to be returned to 
Medtronic at the end of the study (the patient 
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need to be tracked since not investigational and 
don’t need to be returned).  
Section 9: Removed requirement for CareLink 
monitors to be tracked since they are not 
investigational and don’t need to be returned to 
Medtronic.  
Section 9: Updated language to clarify 
documentation requirements associated with 
installation/removal of the investigational 
RAMware from the devices and programmers.  
Section 9.1: Updated Table 9 to include 
subsequent versions of the investigational 
RAMware since the CIP now allows for 
subsequent versions of the RAMware to be 
utilized in the study.  
Section 11: Added SADE definition to Table 10 
for completeness.  
Section 11: Updated Table 10 to remove note 
that only system or procedure related AEs will be 
classified as a complication or observation, since 
these are the only types of AEs being collected in 
the study.  
Section 11.2.1: Added clarification that deaths 
will be reported via a Subject Death form.  
Section 11.2.2: Added clarification that device 
deficiencies that result in an ADE should be 
captured on an AE form.  
Section 11.3: Updated Table 11 to correct 
“Severity” to “Seriousness”, and to remove 
language stating that SAEs and UADEs would be 
adjudicated as complications/observations by the 
sponsor, since this will be performed by the CEC.  
Section 11.6: Clarified scope of CEC 
adjudication.  
Section 14.2.4: Corrected HF event probability 
(due to error in CIP v1.0). 
Section 18.1: Removed “Subject screening log (if 
applicable)” from list of investigator records, 
since not required to be maintained for this study. 
Section 18.1: Added “if applicable” to 
requirement for maintaining non implantable 
product traceability records, since not required in 
all cases (e.g. CareLink monitors and patient 
assistants provided to subjects are not required 
to be tracked).  
Section 18.4: Updated Table 16 to remove 
requirements for reporting to FDA, since the 
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and therefore the study was not submitted to 
FDA. 
Appendix A: Updated text to remove “draft” since 
final version of CRFs now available.  
Appendix E: Removed statement that site 
confirmation was not finalized since now 
complete, and clarified that a site list would be 
provided under separate cover. 
Appendix F: Removed statement that site 
confirmation was not finalized since now 
complete, and clarified that an IRB list would be 
provided under separate cover. Also added 
statement that information will be updated 
throughout study and updated listing will be 
available upon request.  
Appendix L: Updated Summary of Changes to 
include changes reflected in CIP v2.0.  
Minor updates to punctuation, grammar and 
formatting throughout document for accuracy, 
clarity and consistency.  
 
 

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Statistical Analysis Plan 
Clinical Investigation Plan Title  Reveal LINQ HF 
Clinical Investigation Plan Version 1.0 
Sponsor/Local Sponsor Medtronic, Inc.  
8200 Coral Sea Street NE 
Mounds View, MN U.S.A. 55112 
1-800-328-2518 
Document Version 1.0 
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 
1. 
Version History .............................................................................................................. 3 
2. 
List of Abbreviations and Definitions of Terms ............................................................. 3 
3. 
Introduction................................................................................................................... 3 
4. 
Study Objectives ............................................................................................................ 4 
5. 
Investigation Plan ......................................................................................................... 4 
6. 
Determination of Sample Size ....................................................................................... 6 
7. 
Statistical Methods ........................................................................................................ 6 
7.1. 
Study Subjects .................................................................................................................. 6 
7.1.1. 
Disposition of Subjects .......................................................................................... 6 
7.1.2. 
Clinical Investigation Plan (CIP) Deviations ............................................................. 6 
7.1.3. 
Analysis Sets ........................................................................................................ 7 
7.2. 
General Methodology ........................................................................................................ 7 
7.3. 
Center Pooling .................................................................................................................. 7 
7.4. 
Handling of Missing Data and Dropouts .............................................................................. 7 
7.5. 
Adjustments for Multiple Comparisons ................................................................................ 7 
7.6. 
Demographic and Other Baseline Characteristics ................................................................. 8 
7.7. 
Treatment Characteristics .................................................................................................. 8 
7.8. 
Interim Analyses ............................................................................................................... 8 
7.9. 
Evaluation of Objectives .................................................................................................... 9 
7.9.1. 
Hypothesis ........................................................................................................... 9 
7.9.2. 
Performance Requirements .................................................................................... 9 
7.9.3. 
Rationale for Performance Criteria .......................................................................... 9 
7.9.4. 
Analysis Methods .................................................................................................. 9 
7.9.5. 
Determination of Patients/Data for Analysis .......................................................... 11 
7.9.6. 
Sample Size ........................................................................................................ 11 
7.10. 
Safety Evaluation ............................................................................................................ 11 
7.11. 
Health Outcomes Analyses .............................................................................................. 12 
7.12. 
Changes to Planned Analysis ........................................................................................... 13 
8. 
Validation Requirements ............................................................................................. 13 
9. 
References ................................................................................................................... 13 
 
 

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1. 
Version History 
 
Version 
Summary of Changes 
Author(s)/Title 
1.0 
• 
Not Applicable, New Document 
Lou Sherfesee, Sr. Principal 
Statistician 
2. 
List of Abbreviations and Definitions of Terms 
Abbreviation 
Definition 
AE 
Adverse Event 
ADHF 
Acute decompensated heart failure 
AF 
Atrial Fibrillation 
AHF 
Acute Heart Failure 
CEC 
Clinical Events Committee 
CIP 
Clinical Investigational Plan 
CRF 
Case Report Form 
CRT 
Cardiac Resynchronization Therapy 
ECG 
Electrocardiogram 
EF 
Ejection Fraction 
HCU 
Healthcare Utilization 
HF 
Heart Failure 
ICD 
Implantable Cardioverter-Defibrillator 
ICM 
Insertable Cardiac Monitor 
IPG 
Implantable Pulse Generator 
NYHA 
New York Heart Association 
RAMware 
Software downloaded onto LINQ™ device 
RR 
R-wave to R-wave interval 
SAE 
Serious Adverse Event 
 
3. 
Introduction 
Medtronic, Inc. is sponsoring the Reveal LINQ™ Heart Failure (HF) study, a prospective, non-
randomized, multi-center, observational, pre-market clinical study.  The purpose of this clinical 
study is to characterize Reveal LINQ™ derived data from patients with heart failure by 
assessing the relationship between changes in LINQ™ derived data and other physiologic 
parameters with subsequent acute decompensated heart failure events (ADHF). 
 

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The study is utilizing the Reveal LINQ™ device with an investigational LINQ™ HF RAMware. 
 
 
 Additionally, the device 
will collect the standard information collected in the market released LINQ™ device such as 
atrial fibrillation burden, average ventricular rate during atrial fibrillation (AF), night and day 
heart rate and heart rate variability. The study will also collect information regarding HF related 
clinical events during the same period. 
 
The data collected via the LINQ HF investigational RAMware will not be provided to sites for the 
treatment of the subjects.  Following insertion of the LINQ™ device and download of the LINQ 
HF investigational RAMware, subjects will be followed for up to 3 years post-insertion or until 
official study closure defined as when Medtronic and/or regulatory requirements have been 
satisfied per the Clinical Investigation Plan and/or by a decision by Medtronic or regulatory 
authority, whichever occurs first.   
 
This Statistical Analysis Plan has been designed to document, for internal use, the Reveal LINQ 
HF Study design and the planned analyses to be included in a final report.  
4. 
Study Objectives 
The primary objective is to characterize Reveal LINQ™ derived data from patients with heart 
failure by assessing the relationship between changes in LINQ™ derived data and other 
physiologic parameters with subsequent ADHF events. 
5. 
Investigation Plan 
The LINQ™ HF study is a Non-Significant Risk Investigational Device Exemption (IDE) 
study. The study is utilizing the Reveal LINQ™ device with an investigational LINQ™ HF 
RAMware download. The LINQ™ HF RAMware enables 
 
 
 
The single-arm observational study is expected to be conducted at up to 30 centers in the 
United States. Up to 300 subjects will be enrolled to achieve approximately 40 ADHF events (no 
more than two per subject will contribute to the cumulative total). Study subjects will be 
followed for up to 3 years post-insertion or until official study closure defined as when 
Medtronic and/or regulatory requirements have been satisfied per the Clinical Investigation Plan 
and/or by a decision by Medtronic or regulatory authority, whichever occurs first. The expected 
study duration is approximately 4 years representing 1.5 years of enrollments and 2.5 years of 
follow-up. 
 

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The subject population for the LINQ™ HF study is patients with heart failure with a New York 
Heart Association (NYHA) Class III. Inclusion and Exclusion criteria are listed below. 
 
INCLUSION CRITERIA 
• 
Patient is 18 years of age or older 
• 
Patient (or patient’s legally authorized representative) is willing and able to provide 
written informed consent 
• 
Patient is willing and able to comply with the protocol, including follow-up visits and 
Carelink transmissions. 
• 
Patient is NYHA Class III 
• 
Patient had a HF event (HF event defined as meeting any one of the following three 
• 
criteria): 
1. Admission with primary diagnosis of HF within the last 6 months, OR 
2. Intravenous HF therapy (e.g. IV diuretics/vasodilators) or ultrafiltration at any 
one of the following settings within the last 6 months: 
- Admission with secondary/tertiary diagnosis of HF 
- Emergency Department 
- Ambulance 
- Observation Unit 
- Urgent Care 
- HF/Cardiology Clinic 
- Patient’s Home, OR 
3. Patient had the following within the last 3 months: EF > 50%, then BNP> 200 ng/L 
or NTpro-BNP > 400 ng/L OR If EF is <50%, then BNP> 400 ng/L or NTpro-BNP > 800 
ng/L 
 
EXCLUSION CRITERIA 
• 
Patient is pregnant (all females of child-bearing potential must have a negative 
pregnancy test within 1 week of enrollment) 
• 
Patient is enrolled in another study that could confound the results of this study, 
without documented pre-approval from a Medtronic study manager 
• 
Patient has severe valvular heart disease as defined by hemodynamically significant 
valve stenosis and/or prosthetic heart valve 
• 
Patient has existing IPG, ICD, CRT-D or CRT-P device 
• 
Patient has severe renal impairment (eGFR <25mL/min) 
 
Subjects will have in-office visits at 1 month post-insertion, as well as 6 and 12 months post-
insertion.  These in-office visits will include NYHA assessment, 6 minute hall walk, 
 
, physical exam, medication assessment, and collection of symptoms 
and temperature.  Blood tests will be performed at the 6 and 12 month visits.  Following the 12 
month visit, there will be no further required in-office visit until the exit visit in which the 
RAMware is removed from the device.  In addition to in-office visits, subjects will perform 
monthly manual CareLink transmissions.  
 

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6. 
Determination of Sample Size 
There are no sample size requirements as this is an observational study. However, 40 ADHF 
events with LINQ device data available for the most recent 30 days prior to the event will be 
collected; up to two events per subject may be used in the analysis, and these events must be 
at least 90 days apart.  While any ADHF event with the requisite device data that occurs prior to 
a subject’s exit may be used in the analysis, the sample size was selected in order that data can 
be derived from an estimated 40 subjects with a ADHF event within 12 months. This provides a 
conservative estimate of the required number of subjects. The CHAMPION study provides a 12 
month KM estimate of HF hospitalization of 30% for Class III subjects1.  To be conservative, it 
is assumed 25% of enrolled subjects will have at least one ADHF event within 12 months. If the 
estimate is used as a binomial proportion, a sample size of 300 subjects would accrue ≥40 
subjects with event within 12 months with > 99% probability. If the proportion of subjects with 
ADHF event is lower than 25%, the probability of at least 40 subjects with at least one ADHF 
event is >88% if the underlying proportion of subjects with event is ≥16%. The projected 
enrollment number of 300 may be readjusted if the frequency of ADHF events is higher or lower 
than anticipated. 
7. 
Statistical Methods 
7.1. 
Study Subjects 
7.1.1. 
Disposition of Subjects 
This is a single-arm study.  Subjects who are consented will undergo a planned standard of care surgical 
procedure.  At enrollment, subjects consent to have a Reveal LINQ inserted and investigational LINQ HF 
RAMware downloaded.  Subjects will then return for 1, 6, and 12 month visits and an exit visit.  A 
STROBE diagram will show each of these stages of follow-up through 12 months, with categories for 
missed visit, death, exit, and early study closure as reasons subjects did not complete a visit.  If the 
study continues beyond 12 months for one or more subjects, there will be a final box with categories for 
death, exit, and study closure as reasons for study discontinuation beyond 12 months. 
7.1.2. 
Clinical Investigation Plan (CIP) Deviations 
Study deviations will result in corresponding Study Deviation eCRFs being completed.  These deviations 
will be summarized with descriptive statistics including, for each type of deviation, how many occurrences 
there were in the study, and the number of subjects experiencing each type of deviation.  
Inclusion/exclusion violations will not result in subjects being excluded from analysis of objectives.  
 
 

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7.1.3. 
Analysis Sets 
All enrolled subjects who undergo a LINQ insertion and investigational LINQ HF RAMware download will 
be included in the analysis of the primary objective. Subjects who do not experience ADHF events used in 
the analysis will still have their data summarized as a reference. 
7.2. 
General Methodology 
Data analysis will be performed by a Medtronic statistician or designee, and will be performed once at 
least 40 ADHF events (as adjudicated by the CEC) occurring at least 30 days post-Reveal LINQ implant 
have been obtained from subjects who received the downloaded RAMware and have data for the most 
recent 30 days prior to the event. No more than two events per subject will be included in the analysis, 
and those two events must be at least 90 days apart. 
All analyses will be performed on an “As Treated” basis. 
The cohort will include all enrolled subjects who received the downloaded investigational LINQ HF 
RAMware and experienced ADHF events at least 30 days post-implant. Subjects who do not experience 
ADHF events may also be included as a reference dataset for baseline readings of measurements (i.e. 
profile of measurements that do not precede ADHF events). 
Any tests of treatment effects will be conducted at a two-sided alpha level of 0.05 unless otherwise 
stated. 
Any change to the data analysis methods described in the protocol will require an amendment only if it 
changes a principal feature of the protocol. Any other change to the data analysis methods described in 
the protocol, and the justification for making the change, will be described in the clinical study report. 
7.3. 
Center Pooling 
Due to the feasibility nature of this study and reduced sample size, statistical comparisons of sites’ 
performance will not be performed.   
7.4. 
Handling of Missing Data and Dropouts 
Missing data will not be imputed. In order to be included in the primary analysis, an ADHF event must 
have LINQ™ data downloads for at least the most recent 30 days prior to the event. If device data are 
missing, the event will not be included in the primary analysis. 
7.5. 
Adjustments for Multiple Comparisons 
No adjustment for multiple comparisons will be made.  This is a single arm study. 

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7.6. 
Demographic and Other Baseline Characteristics 
Descriptive statistics will be used to summarize baseline and demographic characterstics.  For categorical 
data such as gender and New York Heart Association classification, counts and percentages will be 
employed, while for continuous variables such as age, means, standard deviation, quartiles, minimum, 
and maximum will be provided.  These statistics will be provided both for all enrolled subjects and for the 
subset of subjects who receive a LINQ device. 
7.7. 
Treatment Characteristics  
Descriptive statistics will be used to summarize all procedure information collected, including 
• 
Time from procedure check-in to subject discharge 
• 
Pre-procedure preparation time 
• 
Procedure time (time subject enters the room to time subject leaves procedure room) 
• 
Insertion time (time from firt incision to skin closure) 
• 
Pre-procedure preparation location 
• 
Procedure location 
• 
Location of inserted device (e.g. parallel to sternum over 4th intercostal space) 
• 
Whether device was sutured 
• 
Closure method used (e.g. staple(s), suture(s)) 
• 
Local anesthesia used 
• 
Antibiotic agent(s) administered pre-procedure and post-procedure 
• 
Location of subject education on their Reveal LINQ system, and total education time 
 
Additionally, the percentage of subjects on CV medications will be assessed as of each follow-up visit.  
This will be done separately for relevant classes such as beta blockers, diuretics, and ACE-
Inhibitors/ARBs. 
 
7.8. 
Interim Analyses  
No interim analyses are planned for this study.  Since there is no interim analysis planned, there are no 
criteria for early termination based on statistical evidence.  Once the requisite number of ADHF events 
have been obtained (a minimum of 40 occurring ≥ 30 days post-implant among subjects with the 
RAMware downloaded to the subject’s LINQ device, with no more than two ADHF events per subject), 
follow-up in the study may be terminated and all subjects exited.   
 

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7.9. 
Evaluation of Objectives 
The primary objective is to characterize Reveal LINQ™ derived data from patients with heart failure by 
assessing the relationship between changes in LINQ™ derived data and other physiologic parameters 
with subsequent ADHF events. 
7.9.1. 
Hypothesis 
Due to the feasibility nature of this trial, there are no hypotheses for this objective.  
7.9.2. 
Performance Requirements 
Performance requirements are not pre-specified for this objective. The ADHF events as adjudicated by 
the CEC that will be used in the primary analysis are those that are ≥30 days following implant in order 
to ensure sufficient LINQ™ derived data prior to the event onset are available. A second ADHF event 
within a subject may be used if the second ADHF event is >90 days following the first event. In the event 
a subject has > 2 qualifying ADHF events, only the first two will be used in the primary analysis.  
Additional analyses including all qualifying ADHF events may be conducted. 
 
A heart failure event is defined as any cardiovascular-related (including hypervolemia) 
Health Care Utilizations (HCUs) for any one of the following events. 
• 
Admission with primary diagnosis of HF 
• 
Intravenous HF therapy (e.g. IV diuretics/vasodilators) or ultrafiltration at any one of the 
following settings: 
o Admission with secondary/tertiary diagnosis of HF 
o Emergency Department 
o Ambulance 
o Observation Unit 
o Urgent Care 
o HF/Cardiology Clinic 
7.9.3. 
Rationale for Performance Criteria 
This is a feasibility study, and so this objective is for the purpose of gathering data for 
 
 
this data will be used later for potential hypothesis generation regarding the predictive 
nature of one or more of these data elements for ADHF outcomes. 
7.9.4. 
Analysis Methods 
Physiologic data (including heart rate, bioimpedance, activity, blood pressure and weight), as well as 
blood samples (including serum BUN, creatinine, NT-proBNP, hemoglobin, hematocrit, troponin, eGFR 
and electrolytes), will be collected from subjects with acute decompensated heart failure.
 
 

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The following table lists out the RAMware features and frequency of measurements. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Data will be collected from enrollment up to 3 years post-insertion. If a subject exits the study 
prematurely, data captured prior to exit will be included in the analysis. All data collected will be included 
in the analysis. Descriptive statistics (e.g. means, standard deviations, proportions) will be used to 
summarize the physiological and derived data recorded. Analyses will be conducted to assess changes in 
the physiologic and LINQ™ derived data in association with HF events. 
For each subject whose device contains the downloaded RAMware, the measurements in the table above 
will be averaged to produce one mean value for each feature for each day.  Then for subjects who 
experience at least one ADHF event, the daily mean values will be averaged across subjects for each day 
leading up to the first event per subject and each day following that event for a minimum of 14 days on 
either side of admission.  For example, if 40 subjects have at least one ADHF event, then for each of the 
14 days prior to that event, the 40 subjects’ mean values for that day will be averaged.  The same will be 
done for the 14 days following ADHF admission.  This will be done for each of the features above. 
For subjects who have multiple ADHF events, plots may be produced with time on the x-axis, and daily 
average value for a particular feature on the y-axis, with periods in which the ADHF events occurred 
noted as well.  The graph may have the following format.  Because the lack of required follow-up visits 
beyond 12 months may result in ADHF events going unreported, a summary of the plot of a single 
subject’s readings over time should include a marker at 12 months to denote the point at which required 
follow-up visits ended for this subject. 

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Subjects who do not experience an ADHF event included in the analysis will have their daily data 
averaged across these subjects for each day post-insertion and plotted as reference for comparison with 
the data summaries described above. 
7.9.5. 
Determination of Patients/ Data for Analysis 
All subjects with a successful insertion will be used in the analysis.  See section 7.4 for handling of 
missing data. 
7.9.6. 
Sample Size 
Due to the feasibility nature of this trial, there is no sample size requirement for this objective. A 
maximum of 300 subjects is allowed.  See section 6 for rationale. 
 
7.10. Safety Evaluation  
All adverse events that are Reveal LINQ™ system-related or procedure-related are reported with onset 
occurring between a subject’s consent and exit will be summarized.  An overall summary table will be 
generated that shows the number of events and number and percentage of subjects that experience 
adverse events for each category of seriousness, complication/observation status, whether the event is 

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an Unanticipated Adverse Device Effect (UADE) or Unanticipated Serious Adverse Defice Effect (USADE), 
and each level of relatedness to the procedure and/or Reveal LINQ™ system. 
Adverse events will each be assigned a Medical Dictionary for Regulatory Activities (MedDRA) term, and 
will be summarized by MedDRA preferred term.  The statistics will include the number of adverse events 
assigned that term, the corresponding number and percentage of subjects who experienced such an 
adverse event.  A second column in the table will include similar statistics for the number of serious 
adverse events for each corresponding MedDRA term, and the number of subjects experiencing those 
serious adverse events.  Separate tables will be done in this way for all adverse events, for just the 
procedure-related adverse events, and the Reveal LINQ™ system-related adverse events. 
If any adverse event is classified by the CEC as an Unanticipated Adverse Device Effect, it will be 
summarized. 
A listing table of all adverse events will also be generated.  Each row will contain the subject ID, the 
MedDRA preferred term, the onset date and days post-procedure, whether the event was a complication 
or observation, whether the event was serious, the relatedness to the procedure or system (if any), a 
summary of actions taken in response to the event, and the outcome of the event (whether it was 
resolved, and the date of resolution). 
7.11. Health Outcomes Analyses  
Healthcare utilizations will be adjudicated by the CEC.  A summary table will be generated showing the 
prevalence of each HCU type.  The format of the table will be as presented below.  All HCUs will be 
included in the table below.  Because multiple HCU’s occurring on the same day will be recorded on one 
HCU form, only the most severe HCU type (using the hierarchy in the table below) will be taken for each 
form.  For example, if a subject presented at the Emergency Department and then is admitted to an 
inpatient hospitalization, that HCU will be considered an inpatient hospitalization for purposes of analysis.   
Healthcare Utilization Type 
Number of HCUs (Number, % of Subjects With HCU) 
All HCUs 
HF-related HCUs 
Inpatient Hospitalization 
X (Y, %) 
X (Y, %) 
Emergency Department Visit 
X (Y, %) 
X (Y, %) 
Hospital Outpatient Clinic Visit 
X (Y, %) 
X (Y, %) 
Other Outpatient Utilization with overnight stay 
X (Y, %) 
X (Y, %) 
Urgent Care visit 
X (Y, %) 
X (Y, %) 
Clinic Visit 
X (Y, %) 
X (Y, %) 
   Scheduled 
X (Y, %) 
X (Y, %) 
   Unscheduled 
X (Y, %) 
X (Y, %) 
Phone Call 
X (Y, %) 
X (Y, %) 
Total Events 
X (Y, %) 
X (Y, %) 
 
Additionally, the monthly rate of heart failure-related HCUs will be determined, allowing for multiple 
events per subject.  The monthly rates will be calculated for each month post-insertion.  For each month 
(e.g. 0-30 days, 31-61 days, etc.), the number of HF-related HCUs occurring in that interval will be 
divided by the total number of follow-up months for that interval (each subject can contribute a minimum 

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of 0 months and a maximum of 1 month for each interval).  The intervals for month K (K=1,2,…,30) will 
be determined by multiplying 30.44 days by K-1 and K and rounding each to the nearest whole number.  
As described above, if multiple HCU types are recorded on one HCU form, this will count as one total 
HCU. 
7.12. Changes to Planned Analysis  
No changes from the CIP-specified analysis are planned, though additional analyses are described in this 
document.  
8. 
Validation Requirements 
Due to the descriptive nature of the analyses, Level II validation will be performed on programs related 
to the primary objective, as well as healthcare outcomes and adverse events.  Level II validation may 
occur for programs summarizing baseline demographics, study deviations, follow-up compliance, and 
study exits. 
9. 
References  
1. Philip B. Adamson, William T. Abraham, Robert C. Bourge, Maria Rosa Costanzo, 
Ayesha Hasan, Chethan Yadav, John Henderson, Pam Cowart, and Lynne Warner 
Stevenson. Wireless Pulmonary Artery Pressure Monitoring Guides Management to 
Reduce Decompensation in Heart Failure With Preserved Ejection Fraction. Circ Heart 
Fail. 2014;7:935-944.