BioMonitor 2 In-Office Setting Insertion Safety and Feasibility Evaluation With Device Functionality Assessment
Conditions: Insertable Cardiac Monitor
Sponsor: Biotronik, Inc.

 
 
Clinical Protocol for the 
BioInsight Study 
 
 
BioMonitor 2 In-Office Setting Insertion Safety and Feasibility 
Evaluation with Device Functionality Assessment 
 
 
 
April 11, 2016 
 
 
 
BIOTRONIK, Inc. 
6024 Jean Road, Lake Oswego, Oregon 97035 
 
 
 
 
This document contains confidential information for use only by investigators and 
clinical sites participating in the clinical study. Therefore, this document should be 
maintained in a secure location and should not be copied or made available for review 
by any unauthorized personnel. 

 
 
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TABLE OF CONTENTS 
1. INTRODUCTION .................................................................................................................................... 5 
1.1 Name of Device .............................................................................................................................. 5 
1.2 Study Overview .............................................................................................................................. 5 
1.3 Background .................................................................................................................................... 5 
1.3.1 Rationale ............................................................................................................................. 6 
1.3.2 BioMonitor Master Study ..................................................................................................... 6 
1.3.3 BioMonitor Single-center AF Detect Study ......................................................................... 7 
1.3.4 Previous Experience with the BioMonitor 2 ........................................................................ 7 
1.4 Device Description.......................................................................................................................... 8 
1.4.1 BioMonitor 2 Device Information ......................................................................................... 8 
1.4.2 Insertion Procedure ............................................................................................................. 9 
1.4.3 Remote Assistant for Patient Triggering ........................................................................... 11 
1.4.4 BIOTRONIK Home Monitoring® ........................................................................................ 12 
2. STUDY DESIGN ................................................................................................................................... 15 
2.1 Study Objectives ........................................................................................................................... 17 
2.1.1 Primary Objective 1 ........................................................................................................... 17 
2.1.2 Secondary Objective 1 ...................................................................................................... 17 
2.1.3 Secondary Objective 2 ...................................................................................................... 17 
2.1.4 Secondary Objective 3 ...................................................................................................... 17 
2.1.5 Additional Data of Interest ................................................................................................. 17 
2.2 Study Size and Duration ............................................................................................................... 18 
2.3 Sample-Size Analysis ................................................................................................................... 18 
2.3.1 Replacement of Subjects .................................................................................................. 19 
2.4 Data Analyses .............................................................................................................................. 20 
2.4.1 Objective Analysis ............................................................................................................. 20 
2.4.2 Trend Analyses ................................................................................................................. 20 
2.4.3 Missing Data ..................................................................................................................... 20 
3. PROTOCOL REQUIREMENTS ........................................................................................................... 22 
3.1 Subject Population........................................................................................................................ 22 
3.1.1 Indications ......................................................................................................................... 22 
3.1.2 Contraindications .............................................................................................................. 22 
3.1.3 Inclusion Criteria ............................................................................................................... 22 
3.1.4 Exclusion Criteria .............................................................................................................. 23 
3.2 Study Procedures ......................................................................................................................... 23 
3.2.1 Study Pre-screening.......................................................................................................... 24 
3.2.2 Enrollment Visit ................................................................................................................. 24 
3.2.3 Insertion ............................................................................................................................ 25 
3.2.4 Wound Check Visit and 90-day Follow-up ........................................................................ 26 
3.2.5 Interim Follow-ups and System Revisions ........................................................................ 27 
4. DATA COLLECTION ........................................................................................................................... 28 
4.1 Electronic Data Capture (EDC) .................................................................................................... 28 
4.2 Electronic Case Report Forms (eCRFs)....................................................................................... 28 
4.3 Data Clarification/Data Quality Control......................................................................................... 29 
4.4 Subject Retention ......................................................................................................................... 29 
4.5 Subject Data Confidentiality ......................................................................................................... 29 
5. RISKS AND RISK MINIMALIZATION ................................................................................................. 30 
6. STUDY ORGANIZATION ..................................................................................................................... 31 
6.6 Sponsor ........................................................................................................................................ 31 

 
 
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6.7 Clinical Events Committee ........................................................................................................... 31 
7. STUDY MONITORING ......................................................................................................................... 32 
7.1 Summary ...................................................................................................................................... 32 
7.2 Study Monitors .............................................................................................................................. 32 
7.3 Monitoring Visits ........................................................................................................................... 33 
7.4 Centralized Monitoring ................................................................................................................. 33 
8. STUDY COMPLETION ........................................................................................................................ 34 
9. ADVERSE EVENTS ............................................................................................................................. 34 
9.1 Reportable Adverse Events .......................................................................................................... 34 
9.1.1 Insertion Procedure-Related Adverse Events ................................................................... 34 
9.1.2 Device-Related Adverse Events ....................................................................................... 35 
9.1.3 Non-Procedure Non-System Related Adverse Events ..................................................... 35 
9.2 Analysis of the Objectives ............................................................................................................ 35 
9.3 Adverse Events for the Analysis of the Primary and Secondary Objectives ................................ 36 
9.3.1 Adverse Events for the Analysis of Primary Objective 1................................................... 36 
9.3.2 Adverse Events for the Analysis of Secondary Objective 1 .............................................. 36 
9.4 Adverse Event Reporting ............................................................................................................. 36 
10. OTHER GENERAL INFORMATION .................................................................................................... 37 
10.1 Protocol Compliance .................................................................................................................... 37 
10.1.1 Protocol Violations ............................................................................................................ 37 
10.1.2 Protocol Deviations ........................................................................................................... 37 
10.2 Study Exits .................................................................................................................................... 38 
10.2.1 Screen Failures ................................................................................................................. 38 
10.2.2 Unsuccessful Insertion Procedures .................................................................................. 38 
10.2.3 Withdrawal of Consent ...................................................................................................... 38 
10.2.4 Subject Death .................................................................................................................... 38 
10.2.5 BioMonitor 2 Removal ....................................................................................................... 39 
10.2.6 Lost to Follow-up ............................................................................................................... 39 
10.2.7 Study Participation Complete ............................................................................................ 39 
10.3 Informed Consent ......................................................................................................................... 39 
10.4 IRB Approval ................................................................................................................................ 39 
10.5 Other Institutions and Physicians ................................................................................................. 40 
11. RECORDS AND REPORTS ................................................................................................................ 41 
11.1 Investigator Records..................................................................................................................... 41 
11.2 Investigator Reports ..................................................................................................................... 41 
11.3 Sponsor Records .......................................................................................................................... 42 
12. REFERENCES ..................................................................................................................................... 44 
APPENDIX A: DEFINITION OF TERMS .................................................................................................... 45 
APPENDIX B: DETAILED PROCEDURES ............................................................................................... 47 
 
 
 
 
 

 
 
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BioInsight Study 
 
PROTOCOL SIGNATURE PAGE 
 
The signature below constitutes the receipt and review of the BioInsight Study protocol and any 
attachments, and provides the necessary assurances that this study will be conducted 
according to all stipulations of the protocol, including all statements regarding confidentiality, 
and according to local legal and regulatory requirements and applicable US federal regulations, 
ICH and GCP guidelines. 
 
 
PRINCIPAL INVESTIGATOR: 
 
 
Signed: 
 
 
 
 
Name (please print) 
 
 
 
 
 
Signature 
 
Date 
 

 
 
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Title: 
BioInsight Study 
Design: 
Multi-center, prospective, non-randomized, post-market study 
Purpose: 
The purpose of this study is to evaluate the safety and feasibility of performing 
the BioMonitor 2 insertion procedure in an office setting. The study will provide 
data to characterize insertion procedure-related adverse events, time and 
resources utilized at insertion, and device functionality post-insertion. In 
addition, the study may provide data to support an application to CMS and 
private insurance for reimbursement of in-office implants of this device. 
Subject Population: 
Subjects indicated for continuous arrhythmia monitoring who are willing to 
undergo the insertion procedure in an office setting. 
Enrollment: 
This study will enroll up to 75 subjects. 
Clinical Sites: 
Up to 7 centers within the United States. 
Primary Objectives: 
Characterization of all insertion procedure-related adverse events within 90 
days post-insertion that require additional invasive intervention to resolve.  
Secondary Objectives: 
 
Characterization of all insertion procedure-related adverse events. 
 
Characterization of the insertion procedure. 
 
Characterization of device functionality post-insertion. 
Clinical Events 
Committee Chair: 
Marye Gleva, M.D., F.A.C.C, F.H.R.S. 
Associate Professor of Medicine 
Department of Cardiology 
Washington University School of Medicine, St. Louis, MO 
Sponsor: 
BIOTRONIK, Inc. 
Clinical Studies Department 
6024 SW Jean Road 
Lake Oswego, Oregon 97035 
 

 
 
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1. INTRODUCTION 
1.1 
NAME OF DEVICE 
This study is designed to investigate the BioMonitor 2, BIOTRONIK’s second generation 
of insertable cardiac monitor (ICM). The BioMonitor 2 is available in one model, the 
BioMonitor 2-AF. 
1.2 
STUDY OVERVIEW 
The purpose of this study is to evaluate the safety and feasibility of performing the 
BioMonitor 2 insertion procedure in an office setting. Data will be collected from up to 75 
subjects from insertion through 90-days of follow-up post-insertion.  
Subjects will be consented within 30 days prior to the insertion procedure and will be 
screened to ensure they meet all of the inclusion and none of the exclusion criteria. 
Subjects with successful insertions will be required to complete an initial wound check 
visit 7 days (window -2, +7 days) after the procedure and a routine follow-up visit at 90 
days (window -15, +30 days) post-insertion. 
The rate of insertion procedure-related adverse events (AEs) within 90 days post-
insertion that require additional invasive intervention to resolve will be assessed. Data 
will also be collected on the safety and feasibility of in-office insertion procedures. 
Additionally, device orientation and insertion techniques, time and resources utilized, 
and device functionality post-insertion will be characterized. 
1.3 
BACKGROUND 
Based on the first generation of BIOTRONIK’s ICM, the BioMonitor 2 utilizes well-
established arrhythmia detection algorithms within smaller hardware. Equipped with 
BIOTRONIK Home Monitoring®, the BioMonitor 2 supports daily transmissions of device 
diagnostics and subcutaneous ECG (sECG) recordings, automatically and through 
patient triggers. The BioMonitor 2, cleared April 11, 2016 (K152995 number), is the 
successor of the BioMonitor with AF detection, cleared March 19, 2015 (K143503).  
 
 
 
 
 
 

 
 
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1.3.1 
Rationale 
ICMs and implantable loop recorders (IRLs) are subcutaneous devices capable of long-
term cardiac rhythm monitoring that are useful in correlating arrhythmias with patient 
symptoms. Most commonly, ICMs are implanted to assist in the diagnosis of 
unexplained palpitations and syncope with more reliable and accurate monitoring than 
traditional 12-channel ECGs. ICMs are also used in the detection and management of 
atrial fibrillation (AF) for patients who are at high thromboembolic risk. ICMs, including 
BIOTRONIK’s first generation BioMonitor, were originally designed after pacemaker 
technology. Current ICMs have significantly decreased profiles, allowing for less-
invasive insertion procedures1 and low complication rates2-3 compared to that of 
pacemakers and implantable cardioverter defibrillators (ICDs).4-5 
In recent years, many minor surgical procedures have moved from traditional hospital 
settings to physician office settings. While performing these procedures outside of a 
hospital environment presents possible additional risks to the patient, the procedures 
are generally lower in cost and utilize fewer resources.6 With increased interest in 
performing procedures on an out-patient basis, few studies explore the safety of 
procedures outside of specialized clinics. Before new procedures can be adopted in an 
office setting, the procedure complexity, capabilities of the new location, and access to 
supplies, must be considered.  
Unlike other cardiac devices, ICMs do not require vascular access. The low associated 
complication rates and simplistic insertion procedures make ICMs ideal candidates for 
in-office device placement. This study explores the safety of the BioMonitor 2 insertion 
procedure in an office setting. The study will provide data to characterize insertion 
procedure-related adverse events, time and resources utilized during insertion, and 
device functionality post-insertion. In addition, the study may provide data to support an 
application to CMS and private insurance for reimbursement of in-office implants of this 
device. 
1.3.2 
BioMonitor Master Study  
The BioMonitor Master Study was conducted to support regulatory approvals of 
BIOTRONIK’s first generation of ICM and is registered on ClincalTrials.gov 
NCT01725568. The objective of this post-market follow-up study was to confirm the 
safety and efficacy of the BioMonitor. There were 152 subjects implanted between 
October 2012 and October 2014 and observed over the course of one year. During the 
study, no serious complications or adverse events related to the BioMonitor were 
reported, and overall performance of BioMonitor was within the expected range.  

 
 
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1.3.3 
BioMonitor Single-center AF Detect Study 
BIOTRONIK conducted an AF Detection clinical study in order to assess the 
performance of the BioMonitor’s AF feature in clinical practice. The ability of BioMonitor 
to detect episodes of AF was quantified in comparison with the gold-standard, expert-
annotated, external Holter ECG recorder. Fifty (50) participants with suspected 
paroxysmal or persistent atrial fibrillation who had been implanted with a BioMonitor 
were additionally equipped with an external Holter ECG recorder.  
Of these 50 participants, 27 showed at least one true AF episode during the 48-hour 
Holter period, with a maximum of 30 distinct, true AF episodes experienced by one 
subject. A total of 131 AF episodes were annotated from 2132.9 hours of Holter ECG 
data. During the execution of the AF Detection study, only one subject had missing 
Holter data, and hence was excluded from the analysis. These sensitivity values were 
used to calculate the 10,000-sample bootstrap (with 71 of 520 replacement) 95% 
confidence interval for AF detection sensitivity. The 95% confidence limits were 88.5 
and 99.1%. The lower 95% confidence interval for AF episode sensitivity of 88.5% 
clearly exceeds the lower 95% confidence interval for AF episode sensitivity of >60% 
requested by FDA. 
1.3.4 
Previous Experience with the BioMonitor 2 
A pilot study of the BioMonitor 2-AF device and associated tools/accessories has been 
completed in Australia. The study followed an open, prospective, single-arm, non-
randomized design. The objective of this study was to provide clinical data of the 
insertion procedure in an electrophysiology or cardiac catheterization laboratory setting, 
and sensing quality of BIOTRONIK’s second generation of ICM, the BioMonitor 2. Data 
of 30 subjects from 5 Australian clinical sites from December 18, 2014 through July 06, 
2015 are included in this summary. There were 22 male and 8 female subjects enrolled 
with a mean age of 63 years. The most common indications for insertion of the 
BioMonitor 2 were syncope and symptomatic or asymptomatic atrial fibrillation.  
The median time between first skin cut to final successful positioning of BioMonitor 2 
was 2.5 minutes. The mean time of the entire implantation procedure was 9.9 minutes. 
Implanting investigators evaluated the tunneling procedure using the fast insertion tool 
(FIT) set comprised of FIT 1 (pocket tool) and FIT 2 (lead support tool). The FIT 1 tool 
was evaluated related to the needed force and grip on the tool, which resulted in a 
rating of good or acceptable in 83% and 100% of the cases respectively. The FIT 2 tool 
was evaluated by the implanting investigator for device loading, insertion, removal and 
overall handling. All assessments were good or acceptable. 

 
 
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The mean R-wave amplitude at the 1-week and 1-month follow-up visit was 0.7 ± 0.4 
mV and 0.8 ± 0.4 mV, respectively. The results show significant superiority to the mean 
R-wave amplitude of the predecessor BioMonitor (0.3 mV). The mean noise burden was 
1.3 ± 2.3 % and 2.3 ± 3.1 % at the 1-week and 1-month follow-up, respectively. The 
results are significantly improved compared to the predecessor device (5.5%). Five 
subjects reported pain in the pocket during the first week after insertion. Medical 
treatment was not needed. One subject had a wound infection which was treated with 
oral antibiotics.  
The results demonstrate safety and efficacy of the insertion procedure and the study 
device. There were no observations of pocket enlargement or device migration during 
the human clinical evaluation.  
1.4 
DEVICE DESCRIPTION 
1.4.1 
BioMonitor 2 Device Information 
BIOTRONIK’s second generation ICM, BioMonitor 2, is a programmable, subcutaneous 
device that monitors multiple parameters used for cardiac arrhythmia identification. In 
conjunction with BIOTRONIK’s Renamic/ICS 3000 Programmer and U.S. market-
released CardioMessenger® devices capable of communicating with the BioMonitor 2, 
the BioMonitor 2 is designed to automatically provide information on the occurrence of 
arrhythmias in a patient. The BioMonitor 2 is significantly smaller than its predecessor 
and has a longer vector length, or electrode spacing. Although its pacemaker shaped 
predecessor achieves good signal quality by intelligent combination of three smaller 
sensing vectors, the signal amplitudes detected by BioMonitor 2 are generally larger 
due to the increased vector size.  
As seen in Figure 1 below, the BioMonitor 2 is comprised of a flexible lead with an 
embedded antenna and a rigid body.  
Figure 1: BioMonitor 2  
 
The structure and material combination allow for ideal device placement that is 
adjustable to individual patient anatomy. The rigid portion measures 55 mm and the 
flexible portion measures 33 mm in length for a full device length of 88 mm. The device 
is 15 mm wide, 6.2 mm thick, weighs 10.1 g, and is 5 cc in volume. The new shape and 

 
 
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the smaller dimensions of BioMonitor 2 allow for significantly smaller incision length 
(approx. 15 mm) compared to the predecessor (approx. 40 mm) and parasternal 
placement, which is located closer to the heart than a typical pacemaker pocket. 
1.4.2 
Insertion Procedure  
The BioMonitor 2 system is comprised of a specialized FIT set, consisting of the FIT 1 
(pocket tool) and FIT 2 (lead support tool), for easy sub-dermal insertion. The insertion 
tool set (as shown in Figure 2) is designed to create a snug pocket for BioMonitor 2, to 
have an ergonomic contour for the physician, and to properly support the flexible lead 
during insertion. 
Figure 2: BioMonitor 2 Insertion Tool Set  
 
BioMonitor 2 is developed for the insertion into a subcutaneous pocket, in the left side of 
the chest. The determined positions are based on the patient’s anatomy and comfort, as 
well as cosmetic considerations. Recommended locations are areas where minimal 
device movement due to positional changes or body and arm movement is expected 
(Figure 3), e.g. locations between the suprasternal notch and the left nipple, generating 
an approximately 45° rotation from the midline (position A) or the left parasternal region 
(position B). Alternatively, a left sub-mammary position can be used (position C). 
 

 
 
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Figure 3: Possible Positions of BioMonitor 2 
 
 
In the selected anatomical position, after application of local anesthetic agent, a small 
incision through the skin is made, avoiding damage to any underlying musculature. The 
incision should be approximately 15 mm wide. The pocket tool (FIT 1) is advanced 
within a sub-dermal plane until the thumb stop approaches the incision, as shown in 
Figure 4a and 4b. After withdrawing the FIT 1 a suitable pocket for the device is formed.  
Figure 4: Insertion of the Pocket Tool FIT 1 
 
The BioMonitor 2 is placed into the support tool, FIT 2, (Figure 5a) and inserted in a 
two-step approach: First the BioMonitor 2 is gripped with the thumb on top of the device 
until it is inserted up to the welding line (Figure 5b). In a second step, the device is 
pushed in with the thumb resting behind the device (Figure 5c). This ensures that both, 
the FIT 2 with the BioMonitor 2, are inserted together straight into the pre-shaped 
pocket. 
 
 

 
 
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Figure 5: Insertion of the BioMonitor 2 with the Support Tool FIT 2 
 
While sliding the support tool FIT 2 out of the pocket, finger pressure is applied to the 
BioMonitor 2 to keep the device in place. For incision closure standard clinical practice 
is advised. The protection of the wound from environmental influences according to 
physician preference finalizes the insertion procedure of BioMonitor 2.  
1.4.3 
Remote Assistant for Patient Triggering 
Many generations of pacemakers as well as the first generation BioMonitor offer the 
possibility to trigger an IEGM or ECG recording, respectively, if a magnet is applied over 
the device. The disadvantage of a magnet is its weight and furthermore the patient 
receives no feedback if the recording was successful or not. Instead, BioMonitor 2 
utilizes a small electronic patient device, the Remote Assistant.  
The Remote Assistant patient device is a hand-held, battery-operated device which 
uses radio-frequency and coil telemetry to communicate with the BioMonitor 2. The 
Remote Assistant is intended for unsupervised patient use away from a hospital or clinic 
to allow the patient to activate storage of cardiac data when a symptomatic event occurs 
or has occurred. The Remote Assistant, shown in Figure 6, activates the data 
management features in the BioMonitor 2 to initiate recording of cardiac event data in 
the device memory by the single, user-operated button located on the middle area of 
the Remote Assistant patient device.  
Figure 6: Remote Assistant Patient Device 
 
 Record button 
 Telemetry status light 
Low battery light 

 
 
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When device is placed over the location of the BioMonitor 2 implant and the record 
button is pressed, the Remote Assistant indicates if telemetry with the device is 
successful by briefly displaying a yellow light signal. The patient can then move the 
Remote Assistant away from their chest and view the green light signal indicating a 
successful recording. 
1.4.4 
BIOTRONIK Home Monitoring® 
The BIOTRONIK Home Monitoring® system provides early detection of arrhythmic 
events like high ventricular rates or syncope and of silent, asymptomatic events like 
atrial fibrillation, through the transmission of periodic (Figure 7) and triggered sECG 
recordings.  
Figure 7: Periodic sECG Transmission Example 
 
The BioMonitor 2 has the capability to transmit messages to the BIOTRONIK Home 
Monitoring Service Center daily so that the responsible physician will have updated data 
on the technical and physiological parameters of the patient every 24 hours. 
BIOTRONIK Home Monitoring® can be used to provide the physician with advance 
reports from the BioMonitor 2 and can process them into graphical and tabular format. 
This information helps the physician optimize the therapy process, as it allows the 
patient to be scheduled for additional clinical appointments between regular follow-up 
visits if necessary.  
Figure 8: BIOTRONIK Home Monitoring® Transmission Path 
 
BIOTRONIK conducted the TRUST study to evaluate the safety and effectiveness of 
BIOTRONIK Home Monitoring®. BIOTRONIK received FDA approval (P050023/S020, 
approved May 12, 2009) of the following labeling claims regarding BIOTRONIK Home 
Monitoring®: 

 
 
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1. BIOTRONIK Home Monitoring® information may be used as a replacement for 
device interrogation during in office follow up visits. 
2. A strategy of care using BIOTRONIK Home Monitoring® with office visits when 
needed has been shown to extend the time between routine, scheduled in office follow 
ups of BIOTRONIK implantable devices in many patients. BIOTRONIK Home 
Monitoring® data is helpful in determining the need for additional in office follow up. 
3. BIOTRONIK Home Monitoring® patients—who are followed remotely with office 
visits when needed—have been shown to have similar numbers of strokes, invasive 
procedures and deaths as patients followed with conventional in office follow ups. 
4. BIOTRONIK Home Monitoring® provides early detection of arrhythmias. 
5. BIOTRONIK Home Monitoring® provides early detection of silent, asymptomatic 
arrhythmias. 
6. Automatic early detection of arrhythmias and device system anomalies by 
BIOTRONIK Home Monitoring® allows for earlier intervention than conventional in office 
follow ups. 
7. BIOTRONIK Home Monitoring® allows for improved access to patient device data 
compared to conventional in office follow ups since device interrogation is automatically 
scheduled at regular intervals. 
In current US market released BIOTRONIK devices, BIOTRONIK Home Monitoring® 
provides event and system information similar to what is currently available during office 
follow-up visits. The BIOTRONIK Home Monitoring® Quick View Summary Report, 
Figure 9, displays rate trends and episode updates with parameters that are transmitted 
every 24 hours. These parameters include technical parameters (battery status, sensing 
amplitudes, and the percentage of noise per day) as well as physiological parameters 
(heart rate, heart rate variability, patient activity) and arrhythmia parameters (atrial 
burden, ventricular heart rate during atrial burden, and the number of episodes). 

 
 
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Figure 9: Quick View Summary for the BioMonitor 2 
 
 
 
 

 
 
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2. STUDY DESIGN 
This multi-center, prospective, non-randomized post-market study is designed to 
evaluate the safety and feasibility of performing the BioMonitor 2 insertion procedure in 
an office setting. All subjects enrolled in the study will be implanted with a US market 
released BIOTRONIK BioMonitor 2. 
Potential subjects will be identified by the investigator from their general patient 
population and must have an approved indication for continuous arrhythmia monitoring 
with an ICM. Subjects will be consented within 30 days prior to the insertion procedure 
and will be screened to ensure they meet all of the inclusion and none of the exclusion 
criteria as outlined in Sections 3.1.3 and 3.1.4. After eligibility is determined and written 
informed consent is obtained, subjects will be considered ‘provisionally enrolled’ until 
they undergo successful insertion, at which time they are considered fully enrolled. 
Subjects must undergo insertion within 30 days of provisional enrollment. Subjects who 
are provisionally enrolled that do not undergo successful insertion within 30 days will be 
considered screen failures, unless the insertion was unsuccessful due to a protocol 
defined procedure-related adverse event or the insertion procedure was aborted after 
local anesthesia was applied. These subjects will be considered fully enrolled and will 
be followed for 30 days to capture any adverse events related to the insertion 
procedure. Device data and protocol-defined adverse events will be collected from the 
date of the first insertion attempt and thereafter through 90 day post-insertion for 
subjects with successful insertion procedures. 
Subjects who undergo successful insertion procedures will be required to complete an 
initial wound check visit 7 days (window -2, +7 days) after the procedure and a routine 
follow-up visit at 90 days (window -15, +30 days) post-insertion. Subjects should be 
seen in-office for all study visits to assess the BioMonitor 2 device and assess for 
adverse events. For subjects with remote monitoring capabilities, a BIOTRONIK Home 
Monitoring® report should be used for the device data collected at any study visit; 
however, the BIOTRONIK Home Monitoring® data must be accompanied with an in-
office visit.  
Figure 10 provides an overview of the clinical study design. Details of subject eligibility 
requirements are noted in Section 3.1 and details of other study specific procedures and 
data collection are noted in Section 3.2 and Section 4.  

 
 
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Figure 10: Study Design Flowchart 
ENROLLMENT
Identify Potential Subject
Will the subject undergo an insertion procedure with a 
qualifying BioMonitor 2 within the next 30 days?
Subject is not 
a candidate.
Screen
Does subject satisfy the inclusion/exclusion criteria?
Enrollment Procedures
Subject provides written informed consent and 
enrollment data is collected. 
subject is provisionally enrolled
Insertion Procedure
Was the insertion procedure successful?
Study Evaluation
Subjects who are fully enrolled, but do not undergo successful 
insertion will be followed for 30 days to capture any adverse events 
related to the insertion procedure. 
For all other fully enrolled subjects, collect required data from the 
following post-insertion evaluations:

Scheduled wound check evaluation at 7 days (-2, +7 day 
window)  post-insertion and follow-up at 90 days (-15, +30 day 
window) post-insertion 

Interim follow-ups for AEs or device removal
INSERTION
VISITS
Subject is a 
screen failure.
Subject is a 
screen failure.
YES
NO 
NO 
YES
Was the insertion unsuccessful 
due to a protocol defined 
procedure-related complication?
-or-
Was the unsuccessful insertion 
procedure aborted after local 
anesthesia was applied?
Subject is fully enrolled
Collect required data during insertion.
NO
YES
NO 
YES
 
 

 
 
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2.1 
STUDY OBJECTIVES 
This study includes the assessment of one primary objective related to the safety of in-
office BioMonitor 2 insertions and several secondary objectives related to the 
associated safety and feasibility. Due to the sample size, there are no pre-specified 
hypotheses tested in this study.  
2.1.1 
Primary Objective 1 
The purpose of primary objective 1 is to characterize all insertion procedure-related 
adverse events that require additional invasive intervention to resolve. All adverse 
events that are considered insertion procedure-related by the investigator will be 
adjudicated by a Clinical Events Committee (CEC) for classification of the adverse 
event (as defined in Section 9). The results will be summarized with respect to category 
and will include event details.   
2.1.2 
Secondary Objective 1 
The purpose of secondary objective 1 is to characterize all insertion procedure-related 
adverse events that are not included in the primary objective. The results will be 
summarized with respect to category and will include event details.  
2.1.3 
Secondary Objective 2 
The purpose of secondary objective 2 is to characterize the insertion procedure. This 
includes the specific device orientation (as defined in Figure 3), final incision size, and 
total procedure duration. The results will be summarized.  
2.1.4 
Secondary Objective 3 
The purpose of secondary objective 3 is to characterize device functionality post-
insertion. This will be achieved by collecting R-wave amplitudes on the day of insertion 
and at any study visit or through a BIOTRONIK Home Monitoring® report if applicable. 
Long-term trends available through BIOTRONIK Home Monitoring® will also be used to 
characterize device functionality through the 90-day study period. The results will be 
summarized and statistically analyzed, where appropriate. 
2.1.5 
Additional Data of Interest 
Additional information may be collected to characterize the study population, implanted 
system, insertion procedure, and progress of the study. When available, the collected 
information may include baseline demographics, medical history, implanted system 
information, device removals, returned product analysis, and compliance. Specifically, 
data of interest may include: 
 Baseline demographics, including age, gender, weight, height, New York Heart 
Association (NYHA) class, ejection fraction, and race and ethnicity (optional) 
 Medical history, including indication for device  

 
 
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 Implanted device information, including date of insertion and serial numbers for the 
BioMonitor 2 device and accessories  
 Noise burden  
 Triggered sECGs 
 Investigator assessment of appropriate sECG classification 
 Resources used during the insertion procedure 
 Overall physician satisfaction and experience with in-office procedures 
 All other protocol-defined adverse events excluded from primary objective 1 and 
secondary objective 1 
 Removal experience, if applicable 
 Results from returned product analysis 
 Compliance to protocol requirements and study visit schedule 
When reporting medical history for most recent ejection fraction and the current NYHA 
class, details regarding the assessments must be obtained within 6 and 3 months prior 
to enrollment respectively. 
2.2 
STUDY SIZE AND DURATION 
During this study, data will be gathered, analyzed, and reported to evaluate the safety 
and feasibility of the BioMonitor 2 in-office insertion procedure. It is anticipated that 75 
subjects will be implanted and followed through a 90 day post-insertion at up to 7 US 
sites with up to 20 subjects at each site.  
2.3 
SAMPLE-SIZE ANALYSIS 
The study is designed to limit the number of subjects involved while still exposing the 
device to a sufficiently large subject population in order to ensure a representative and 
statistically meaningful sample.  

 
 
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Table 1 demonstrates the precision in estimating the primary objective 1 adverse event 
rate with the sample size of 75 subjects. 
Table 1: Precision in Estimating Adverse Event Rates: Exact 95% Confidence 
Intervals 
Number of 
Events 
Rate 
Confidence Intervals 
(CI) 
1 
1.3% 
(0.0%, 7.2%) 
2 
2.7% 
(0.3%, 9.3%) 
3 
4.0% 
(0.8%, 11.3%) 
4 
5.3% 
(1.5%, 13.1%) 
5 
6.7% 
(2.2%, 14.9%) 
6 
8.0% 
(3.0%, 16.6%) 
7 
9.3% 
(3.8%, 18.3%) 
8 
10.7% 
(4.7%, 20.0%) 
9 
12.0% 
(5.6%, 21.6%) 
10 
13.3% 
(6.6%, 23.2%) 
20 
26.7% 
(17.1%, 38.1%) 
 
The sample size required to assess primary objective 1 is based on an exact, point 
estimate and one-sided upper 95% confidence interval. The sample size for primary 
objective 1 was calculated based on the following assumptions:  
The standard normal approximation to the 95% confidence interval associated with an 
estimate of a binomial parameter (p) is given by: 
 
95% Confidence Interval:      p   ±    1.96  [ p (1 – p) / n ] ½   
 
For example, if there were 4 adverse events out of 75 cases, the observed adverse 
event rate would be 5.3% and the exact binomial calculation would result in a 95% CI of 
(1.5%, 13.1%). 
 
2.3.1 
Replacement of Subjects 
A maximum loss to follow-up of 2% of the total sample size is estimated. The attrition 
rate encompasses all cases of subject exits prior to study completion, and will include 
any subject exits. This includes death, device explants, subject directed withdrawals, 
physician-directed withdrawals, and loss of contact with the subject. Subjects who are 
provisionally enrolled that do not undergo insertion and are considered screen failures 
are not included in attrition. In order to ensure a sufficient population size for data 
analysis, subjects who exit prior to insertion or are determined to be screen failures may 
be replaced as long as enrollment is ongoing. This includes subjects who were 
determined to be ineligible for insertion or withdrew from the study prior to the 
application of local anesthesia during the insertion procedure. These subjects do not 
count toward the overall planned subject number of 75. 

 
 
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2.4 
DATA ANALYSES 
Descriptive statistics will be used to present and summarize the data collected in the 
clinical study. Frequency distributions and cross tabulations will be presented for 
discrete variables. Means, standard errors, and ranges will be presented for continuous 
variables. 
2.4.1 
Objective Analysis 
Primary objective 1 will be assessed by performing an exact, point estimate and one-
sided upper 95% confidence interval for the rate of insertion procedure-related adverse 
events requiring invasive intervention within 90 days of insertion. All p-values of 0.05 or 
lower will be considered evidence of statistical significance.  
Secondary objective 1, which includes all other procedure-related AEs that are excluded 
from primary objective 1, will be summarized with respect to categorized AE rates with 
their associated, exact, 95% confidence interval.  
Other secondary objectives, which include the characterization of the insertion 
procedure and device functionality, will be analyzed quantitatively and statistically where 
appropriate. All available results will be categorized and summarized. With respect to 
device functionality, values will also be grouped by visit (enrollment, 90-day follow-up, 
and interim follow-ups as appropriate). 
2.4.2 
Trend Analyses 
The primary objective is assessed at 90 days post-insertion using a point-estimate and 
one-sided upper 95% confidence interval. The Kaplan-Meier survival curve method will 
be used to estimate the adverse event rate at 90 days post-insertion procedure if at 
least 1 event is observed. Root causes for any failures, regardless of the incidence 
rates, will be investigated. Long-term device functionality trends may be collected and 
analyzed from available BIOTRONIK Home Monitoring® reports from insertion through 
the 90-day follow-up.  
2.4.3 
Missing Data 
All possible steps will be taken to minimize missing data in the study. This includes but 
is not limited to monitoring of study forms for completeness and supporting efforts to 
track and maintain contact with study subjects during the follow-up period.  
The reasons for any missing data in the study will be documented. In cases of missing 
device data, BIOTRONIK Home Monitoring® will be used to impute the missing data 
points. When available, missing data will be imputed with BIOTRONIK Home 
Monitoring® values obtained from the device on the day of a completed follow-up, target 
date of a missed follow-up, or the next closest day in the visit window. 

 
 
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With respect to the assessment of the primary objective, only subjects who experience 
an adverse event associated with the insertion procedure that requires invasive 
intervention to resolve will be compared to subjects that complete the 90-day follow-up. 
The secondary objective, which includes other AEs associated with the insertion 
procedure excluded from the primary analyses, will be assessed in a similar manner. 
There will be no imputation for these missing adverse event outcomes. Home 
Monitoring® reports will be accepted for device data to support the secondary objectives 
in the event that the subject is lost to follow-up. 

 
 
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3. PROTOCOL REQUIREMENTS 
3.1 
SUBJECT POPULATION 
The investigator is responsible for screening all potential subjects and selecting those 
who are appropriate for study inclusion. Potential subjects will be evaluated against the 
inclusion and exclusion criteria described below in Sections 3.1.3 and 3.1.4. The 
subjects selected for participation should be from the investigator's general patient 
population according to the same inclusion and exclusion criteria. 
3.1.1 
Indications 
The BioMonitor 2 is an ICM that records subcutaneous ECG (sECG) and is indicated 
for: 
 Patients with clinical syndromes or situations at increased risk of cardiac arrhythmias 
 Patients who experience transient symptoms that may suggest a cardiac arrhythmia 
 The device has not been tested for and it is not intended for pediatric use  
3.1.2 
Contraindications 
There are no known contraindications for the insertion of the BioMonitor 2. However, the 
patient’s particular medical condition may dictate whether or not a subcutaneous, 
chronically inserted device can be tolerated. 
3.1.3 
Inclusion Criteria 
To support the objectives of this study, the inclusion criteria at the time of subject 
enrollment include the following requirements: 
 Indicated for continuous monitoring with an insertable cardiac monitor 
 Willing to be implanted in an office setting with only local anesthetic available 
 Able to understand the nature of the study and provide informed consent 
 Able and willing to complete all routine follow-up visits at the study site for the 
expected 90-day follow-up 
 Able and willing to use a CardioMessenger® capable of communicating with the 
BioMonitor 2 
 Age greater than or equal to 18 years 
At the time of insertion, the following pre-procedure criteria must be met for the subject 
to undergo insertion: 
 Most recent INR value (within 7 days) is less than 3.5 if currently taking warfarin 
 Absence of infection with no history of infection within the last 30 days 
 

 
 
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3.1.4 
Exclusion Criteria 
To support the objectives of this study, the exclusion criteria at the time of subject 
enrollment include the following requirements: 
 Compromised immune system or at high risk of developing an infection  
 Abnormal thoracic anatomy or scar tissue at the implant site that may adversely 
impact the insertion procedure 
 Enrolled in any investigational cardiac device trial  
 Currently indicated for or implanted with a pacemaker, ICD device, or hemodynamic 
monitoring system 
 Currently implanted with an ICM or ILR 
 Life expectancy less than 6 months 
 Patients reporting pregnancy at the time of enrollment 
3.2 
STUDY PROCEDURES 
Subjects will be fully enrolled at the time of insertion of a BIOTRONIK BioMonitor 2 ICM. 
BIOTRONIK Home Monitoring® should be activated in all subjects. All subjects must be 
seen in-office for all follow-up intervals regardless of remote monitoring activation, but 
the device data should be provided via BIOTRONIK Home Monitoring®. Device data 
from BIOTRONIK Home Monitoring® should be chosen from a transmission on or before 
the date of the in-office visit, no more than seven days prior to the date of visit. 
Additionally, subjects with unsuccessful insertion procedures as outlined in Section 
3.2.3 will be followed for a period of 30 days to capture any adverse events related to 
the insertion procedure. At the end of the 30-day safety period, a follow-up visit or 
phone call will be required to assess for adverse events. 
Study Procedure Visits: 
 Enrollment (subjects are considered provisionally enrolled until undergoing insertion) 
 Insertion  
 Wound check visit 7 (window -2, +7) days post-insertion 
 Routine follow-up evaluations at 90 (window -15, +30) days post-insertion 
 Interim evaluations  

 
 
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Table 2 summarizes the visit assessment schedule. 
Table 2: Study Visit Assessment Schedule 
 
Enrollment 
Insertion1 
Wound 
Check Visit2 
90-day 
Follow-up2 
Interim 
Evaluation  
(if applicable)2,3 
Informed Consent 
(enrollment) 
X 
 
 
 
 
Demographics and 
Medical History 
X 
 
 
 
 
Implant Information 
with Device Evaluation 
 
X4 
 
 
 
Device Evaluation 
 
 
X 
X 
X 
Device Data Read Out 
 
 
 
X5 
 
Triggered Events 
 
 
X 
X 
X 
Adverse Event 
Assessment 
 
X 
X 
X 
X 
Complete eCRF 
X 
X 
X 
X 
X 
1Insertion must be completed within 30 days of provisional enrollment/informed consent. 
2Subjectsusing BIOTRONIK Home Monitoring® should provide device data via BIOTRONIK Home Monitoring® for any study visit, 
but still must be seen in-office for AE assessment 
3Interim follow-up information is collected as defined in 3.2.5. 
4If the insertion procedure is unsuccessful due to a procedure-related adverse event or is aborted after anesthesia is applied, the 
subject will be followed for a period of 30 days to capture any adverse events related to the insertion procedure.  
5Detailed instructions provided in Appendix B. 
3.2.1 
Study Pre-screening 
Prior to enrollment, the patient’s medical history must be reviewed in order to ensure 
they are an appropriate candidate for the study. Subjects taking any oral anticoagulant 
(OAC) may be asked to hold their medication prior to the insertion procedure at the 
discretion of the implanting physician. In addition, all patients must satisfy the study 
inclusion and exclusion criteria prior to enrollment, including being a candidate for a 
BIOTRONIK BioMonitor 2 ICM. 
3.2.2 
Enrollment Visit 
If the patient has been determined to be eligible for the study, informed consent must be 
obtained from the patient prior to initiating any study related procedures. The consent 
process, including discussion of the study, should be documented in the patient’s 
medical or study records.  

 
 
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The following data collection and reporting procedures are performed at enrollment: 
 Obtain Informed Consent 
 Collect subject demographics (gender, height, weight, etc.) 
 Medical history of subject, including device implant indications 
 Complete all required eCRFs 
3.2.3 
Insertion 
Insertion will take place in an office setting. The insertion may be completed on the 
same day as informed consent or within 30 days after. If the subject is taking OACs at 
the time of enrollment, the implanting physician will decide how long they may need to 
hold their medication and the subject may not be able to undergo the BioMonitor 2 
insertion on the same day. BioMonitor 2 will be inserted on the left chest side as 
described in Section 1.4.2. The physician performing the insertion will also determine 
the optimal device position for each subject, as described in Figure 3. 
Subjects are considered provisionally enrolled until they are successfully implanted with 
the BioMonitor 2, at which time they are considered fully enrolled. Subjects who are 
provisionally enrolled that do not undergo successful insertion procedures within 30 
days will be considered screen failures, unless the insertion was unsuccessful due to a 
protocol defined procedure-related adverse event or the insertion procedure was 
aborted after local anesthesia was applied. These subjects will be considered fully 
enrolled, included in the intention-to-treat (ITT) population, and followed for 30 days 
post-insertion to capture any adverse events related to the insertion procedure. At the 
end of the 30-day safety period, a follow-up visit or phone call will be required to assess 
for adverse events. 
The following data collection and reporting procedures are performed at insertion: 
1. Confirm the subject meets the pre-procedure inclusion criteria: 
 Most recent INR value (within 7 days) is less than 3.5 if currently taking warfarin  
 Absence of infection with no history of infection within the last 30 days 
2. Collect insertion information. 
 Date of procedure 
 Method and approach including: 
o Device orientation (as described in Figure 3) 
o Final incision size (measured with a suitable tool) 
o Insertion procedure time (measured from incision to last suture) 
 Procedure success 
3. Collect device serial numbers for the BioMonitor 2, CardioMessenger®, and Remote 
Assistant. 

 
 
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4. Record initial R-wave amplitudes as outlined in Appendix B. 
5. Record any insertion procedure-related and device-related adverse events during 
insertion and complete an Adverse Event eCRF. Insertion procedure-related 
adverse events should be reported even if the insertion attempt is unsuccessful. 
6. Program BioMonitor 2 parameters to best suit the needs of the subject. 
7. Interrogate and print the final programmed parameters. 
8. Complete all required eCRFs. 
3.2.4 
Wound Check Visit and 90-day Follow-up 
Subjects will undergo an assessment of their device at a wound check visit 7 days post-
insertion (window -2, +7 days) and a 90-day follow-up after insertion (window -15, +30 
days). BIOTRONIK Home Monitoring® transmissions should be used for the device data 
at any follow-up, including the wound check and 90-day visit; however, an in-office visit 
to support an AE assessment and other protocol requirements will still be required. 
Device data from BIOTRONIK Home Monitoring® should be chosen from a transmission 
on or before the date of the in-office visit, no more than seven days prior to the date of 
visit. 
Each site Principal Investigator (PI) will be trained to identify and schedule follow-ups to 
meet the required expectation. Additionally, the Electronic Data Capture (EDC) system 
will provide assistance in identifying properly scheduled follow-up visits according to this 
protocol. 
The following study procedures are performed at the wound check visit and 90-day in-
office follow-up: 
1. Obtain BIOTRONIK Home Monitoring® Cardio Report from a transmission on or 
before the date of the in-office visit, and within seven days prior to the date of visit if 
available. 
2. Activate the Remote Assistant and wait approximately 2 minutes.  
3. Interrogate the BioMonitor 2 and print initial programmed parameters and view 
stored diagnostic data. 
4. Record the daily average R-wave amplitudes and corresponding date through 
BIOTRONIK Home Monitoring®. If BIOTRONIK Home Monitoring® is not available, 
record the R-wave amplitudes as described in Appendix B. 
5. Record the daily average noise percentage through BIOTRONIK Home Monitoring®. 
If BIOTRONIK Home Monitoring® is not available, record the noise percentage as 
described in Appendix B. 
6. If there have been any triggered events or alerts since the subject was last seen, not 
including the recording triggered at the visit: 
 Evaluate cause of patient triggers. 

 
 
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 For non-patient triggers, determine if the rhythm associated with the trigger 
classification is able to be confirmed, when possible, using methods such as 
surface ECG verification, symptoms indicative of rhythm, etc. If any triggers were 
suspected to be inappropriate, document the suspected reason(s). 
7. Determine if there have been any adverse events (as defined in Section 9). If any 
are recorded, complete an Adverse Event eCRF. 
8. Program other parameters to best suit the needs of the subject. 
9. At the 90-day follow-up visit perform a device data “Read out” to print and store the 
BioMonitor 2 data as described in Appendix B. 
10. Interrogate and print the final programmed parameters. 
11. Review and complete the appropriate eCRFs. 
3.2.5 
Interim Follow-ups and System Revisions 
Interim follow-ups may occur anytime during the study, at the request of the investigator 
or subject, as a result of a triggered sECG or BIOTRONIK Home Monitoring® alert, etc. 
Anytime a subject’s device is interrogated for any reason during the 90-day study 
period, data should be collected (as outlined in Section 3.2.4) and an interim Follow-up 
eCRF completed. In the event of a subject evaluation to assess for a protocol-defined 
adverse event, in which a device interrogation does not occur, an interim Follow-up 
eCRF does not need to be completed, but adverse event data should be captured on 
the Adverse Event eCRF. Other hospital or clinic visits that are unrelated to the device 
or insertion procedure are not required to be collected.  
Any system revision that is performed after successful insertion of the device but prior to 
the 90-day follow-up has to be documented in the study. A system revision is defined as 
any reposition or removal of the original inserted BioMonitor 2. In the event of a system 
revision, a System Revision eCRF is required as well as the following data: 
 Reason for reposition or removal 
 Date of reposition or removal 
 Type of revision  
 Location of revision (clinic, hospital, office, etc.) 
 Outcome of revision (including type of replacement and device manufacturer, if 
applicable) 
In the event of a reposition, the new device orientation will also be collected.  
 

 
 
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4. DATA COLLECTION 
4.1 
ELECTRONIC DATA CAPTURE (EDC) 
MedNet Solutions Incorporated is a privately held company that specializes in web-
based clinical data management technology. MedNet will host the EDC system and 
provide a secure environment that is accessible to authorized individuals through the 
internet. BIOTRONIK will implement a study specific configuration using this software to 
meet the data collection requirements of the protocol. The EDC system is 21 CFR Part 
11 compliant and is the platform for electronic Case Report Form (eCRF) data entry, 
clinical data discrepancy resolution, and access to reports for BIOTRONIK, specified 
study sites, and any other parties authorized by BIOTRONIK. 
4.2 
ELECTRONIC CASE REPORT FORMS (ECRFS) 
Original data will be collected at each study site and recorded into the EDC system. 
BIOTRONIK will audit source data and monitor completed investigator locked eCRFs.  
The investigator will be required to use an electronic signature to approve the content of 
the data reported in the eCRFs. 
Information from electronically delivered source data (e.g. programmers) will be 
captured and stored in a validated environment. 
Subject follow-up is required for all subjects fully enrolled in this clinical study. The 
required follow-up visit dates are based on BioMonitor 2 insertion date, and are to be 
used for the calculation of the dates of the routine follow-up schedule. The following 
eCRFs will be available in the EDC system: 
 Informed Consent 
 Informed Consent Update 
 Enrollment  
 Insertion  
 Wound Check Visit (-2, +7 day window) 
 90-day Follow-up (-15 , +30 day window) 
 Interim Follow-up  
 Adverse Event 
 System Revision 
 Study Exit 
 Protocol Noncompliance 
 Data Clarification 

 
 
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4.3 
DATA CLARIFICATION/DATA QUALITY CONTROL 
BIOTRONIK will review study data. At any time, reports can be generated on data 
completion and missing data for each study site. An EDC system will be used to track 
received and expected follow-up data and eCRFs for each participant. This system 
provides the capability to monitor the status, volume, and disposition of data as well as 
to identify data completed, due, overdue, and backlogged. In addition, all study data will 
undergo automatic edit and plausibility checks, which provide information to the study 
sites to help improve and maintain data quality control procedures designed to detect 
inaccuracies and inconsistencies.  
To ensure protocol compliance at all participating study sites, BIOTRONIK monitors will 
conduct monitoring visits (see Section 7).  
To ensure compliance with federal regulations, internal policies and procedures, and the 
study protocol, the EDC vendor will routinely be monitored and/or audited by 
BIOTRONIK or a BIOTRONIK representative as required by BIOTRONIK standard 
operating procedures (SOPs). 
4.4 
SUBJECT RETENTION 
Due to the relatively small population size, subject attrition is not considered to be a 
challenge. A maximum loss to follow-up of 2% of the total sample size is estimated. 
BIOTRONIK will provide additional tools to the sites in an effort to minimize the number 
of subjects that are lost to follow-up. The EDC system includes an overview of each 
subject’s follow-up schedule, including the windows for each follow-up. The EDC 
system also provides a subject follow-up tool in the form of a Follow-up Compliance 
Detail Report. This report allows research personnel to become alerted to and track all 
study subjects that should be scheduled for upcoming follow-ups.  
4.5 
SUBJECT DATA CONFIDENTIALITY 
All information sent to BIOTRONIK pertaining to each subject will be kept confidential at 
BIOTRONIK and is subject to FDA audit. Source documents used to support study 
objectives adjudication by the CEC will have all confidential subject identifiers redacted 
prior to being provided to the CEC. Reports submitted to the physician and publications 
of study results will not make any reference to subject names. 
In order to verify the study data and ensure study integrity, monitors from BIOTRONIK, 
the FDA, and the reviewing Institutional Review Board (IRB) may review and/or copy 
the study records. 
 
 

 
 
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5. RISKS AND RISK MINIMALIZATION 
All devices included in this study are legally marketed and being prescribed by 
physicians according to FDA approved indications for use. 
As with any implantable device, there are always potential risks that accompany the 
device. The following list provides the potential risks that may occur with the use or 
insertion of the BioMonitor 2: 
 Device failure 
 Device migration 
 Device rejection phenomena (including local tissue reaction) 
 Excessive bleeding 
 Fluid accumulation within the device pocket 
 Hematoma 
 Infection 
 Pocket pain 
 Skin erosion 
These risks can be minimized through use of strict aseptic technique, compliance with 
the study protocol and technical insertion procedures, adherence to the guidelines for 
selection of subjects, close monitoring of the subject’s physiologic status during 
insertion and follow-up procedures, and by promptly supplying BIOTRONIK with all 
pertinent information required by this protocol.  
As excessive bleeding is of particular concern with in-office procedures, subjects taking 
warfarin or any other OAC may be asked to hold their medication prior to the insertion 
procedure at the discretion of the implanting physician. 
BIOTRONIK foresees no additional risks associated with this study beyond those stated 
in the labeling for device. 
 

 
 
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6. STUDY ORGANIZATION 
6.6 
SPONSOR 
BIOTRONIK is the "sponsor" of the BioInsight Study.  A "sponsor" is defined as an entity 
that initiates but does not conduct a study.  BIOTRONIK’S responsibility as the clinical 
study sponsor is to ensure protocol and regulatory compliance through proper 
monitoring of the study.  BIOTRONIK is required to ensure that the device is used under 
the immediate direction of an investigator.  As the investigator, the physician is 
responsible for conducting the study in accordance with the signed agreement, the 
study protocol, applicable laws, FDA regulations, and any conditions of approval 
imposed by the reviewing IRB.   The primary investigator must also accept responsibility 
for all aspects of the study including the actions of any co-investigators participating in 
the study at the study site. 
6.7 
CLINICAL EVENTS COMMITTEE  
A Clinical Events Committee (CEC) consisting of at least 3 independent 
electrophysiologists will be established to review and adjudicate adverse events that 
occur during the study. The CEC will be blinded to the clinical study site and subject 
identity, and to minimize bias, members will not participate as investigators. The CEC 
will create a study specific charter defining the adverse event adjudication process, 
specifically detailing review guidelines along with appropriate response timelines. 
All protocol defined adverse events (see Section 9.1) will be adjudicated by the CEC. 
The CEC will classify the adverse event and indicate whether the adverse event is 
related, possibly related, not related, or has an unknown relation to the BioMonitor 2 
insertion procedure. The CEC will also have the responsibility to adjudicate the type of 
adverse event (insertion procedure-related, device-related, and non-procedure non-
system related) and specific category (Section 9.1).  

 
 
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7. STUDY MONITORING 
7.1 
SUMMARY 
BIOTRONIK’s responsibility as the clinical study sponsor is to ensure protocol and 
regulatory compliance through proper monitoring of the study. BIOTRONIK requires IRB 
review and a subject Informed Consent Form for all after-market research. Monitoring 
may be conducted on-site at the study site or remotely by BIOTRONIK monitors.  
Through on-site or centralized monitoring, BIOTRONIK will assess the site’s 
performance in the following areas:  
 Verification that informed consent was obtained  
 Adherence to protocol eligibility criteria and requirements 
 Documentation of performed procedures and assessments related to: 
 Study objectives 
 Protocol required safety assessments 
 Evaluating, documenting, and reporting subject deaths and withdrawals, 
especially when a withdrawal may be related to an adverse event. 
 Investigator oversight and delegation of authority to study personnel 
 Verification of study-specific required documentation 
 Conduct and documentation of procedures essential to trial integrity 
 Adherence to the applicable FDA regulations regarding the obligations of the 
investigator and maintenance of records. 
As the investigator, the physician is responsible for conducting the study in accordance 
with the signed agreement, the study protocol, applicable laws, FDA regulations, and 
any conditions of approval imposed by the reviewing IRB. The principal investigator 
must also accept responsibility for all aspects of the study including the actions of any 
sub-investigators participating in the study at the study site. 
7.2 
STUDY MONITORS 
Study monitors are trained, qualified, and designated by BIOTRONIK management to 
oversee the progress of a study at the study site. Additional monitors may be appointed 
as necessary. 

 
 
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The address to submit study information to BIOTRONIK is: 
BIOTRONIK, Inc. 
Attn: BioInsight Study 
Clinical Studies Department 
6024 Jean Road 
Lake Oswego, Oregon 97035 
Study information may also be submitted by fax to: (800) 723-9220 
For study assistance, call: (800) 547-0394 
For technical assistance 24 hours a day, call: (800) 547-0394 
7.3 
MONITORING VISITS 
A monitor will conduct monitoring visits at study sites in accordance with the Monitoring 
Plan. Sites are required to support these visits and the study monitoring effort. On-site 
monitoring visits will also provide an assessment of the continued acceptability of the 
facilities to continue participation in the study.  
7.4 
CENTRALIZED MONITORING  
Centralized monitoring will be conducted throughout the course of the study in 
accordance with the Monitoring Plan. Some examples of data that may be monitored 
remotely include: informed consent forms, insertion and device data, and adverse 
events reported in the EDC system. Sites are required to support centralized monitoring 
by providing source documents to BIOTRONIK in order to source data verify data 
reported in the EDC system and resolving queries in a timely manner.  
 

 
 
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8. STUDY COMPLETION 
BIOTRONIK will notify the study site upon completion or termination of the study or 
investigator’s participation in the clinical study. At BIOTRONIK’s request, an investigator 
will return any devices, equipment and pertinent information in their possession.  
BIOTRONIK will provide a final report to each study site. The investigator must retain 
records related to the study for a period of 2 years after the study is completed. 
9. ADVERSE EVENTS 
The rate of insertion procedure-related adverse events (AEs) within 90 days post-
insertion that require additional invasive intervention to resolve will be assessed. 
Additional data will be collected on the safety and feasibility of in-office insertion 
procedures. 
An AE is defined as any unfavorable and unintended event that occurs during the 
course of the study. The investigator will be required to assess and classify the type of 
each reported adverse event as insertion procedure-related, device-related, or non-
procedure non-system related. Only adverse events occurring in fully enrolled subjects 
on or after the date of insertion through the duration of the study will be collected. If the 
insertion procedure is unsuccessful due to a procedure-related adverse event or is 
aborted after anesthesia is applied, the subject will be followed for a period of 30 days 
to capture any additional adverse events related to the insertion procedure. 
The study site should report each adverse event via an Adverse Event eCRF and 
provide a copy of the IRB adverse event notification to BIOTRONIK.  
9.1 
REPORTABLE ADVERSE EVENTS 
All insertion procedure-related, device-related and non-procedure non-system related 
AEs will be reported. The following AEs categories, sorted by type, will be reported. The 
types listed below are general classifications for site reporting purposes. Detailed 
information for specific categories is located in Appendix A. Final categories will be 
determined by the CEC. The CEC charter may include alternate classifications for some 
adverse events. 
9.1.1 
Insertion Procedure-Related Adverse Events 
The AE type will be classified as procedure-related if any one of the following occurs as 
a result of the insertion procedure: 
 Device damage 
 Excessive bleeding 
 Fluid accumulation within the device pocket 
 Hematoma 

 
 
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 Inability to create pocket 
 Non-healing pocket dehiscence requiring intervention  
 Pocket pain 
 Primary infection 
 Superficial infection 
 Surrounding tissue damage 
9.1.2 
Device-Related Adverse Events 
The AE type will be classified as device-related if any one of the following occur: 
 Device failure 
 Device migration 
 Device protrusion 
 Device rejection phenomena  
 Skin erosion 
9.1.3 
Non-Procedure Non-System Related Adverse Events 
The AE type will be classified as non-procedure non-system related if any of the 
following occur and require device removal: 
 Secondary infection 
 Other non-elective intervention 
9.2 
ANALYSIS OF THE OBJECTIVES 
All protocol defined AEs included in the primary and secondary objective analysis will be 
adjudicated by the Clinical Events Committee (CEC) (see Section 2.1). For each AE, 
the CEC will classify the relatedness to the insertion procedure as not related, related, 
possibly related, or unknown. The CEC will also have the responsibility to adjudicate the 
type (insertion procedure-related, device-related, or non-procedure non-system related) 
as well as the specific category of each reported AE (see Section 9.1).   
In assessment of the primary objective, the estimate of AE rates will be based on the 
number of subjects with at least one AE adjudicated as related to the insertion 
procedure as a proportion of total subjects. Events with a final AE adjudication of 
possibly related, not related or unknown relatedness classification will not contribute to 
or be included in the assessment of the primary objective. AEs related to the insertion 
procedure that require additional invasive intervention to resolve are included in primary 
objective 1. The same rules will be used for purposes of Kaplan-Meier survival 
analyses, described in Section 2.4.2.  

 
 
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Secondary objective 1, which includes AEs that were excluded from primary objective 1 
through 90 days post-insertion, will also be summarized as AE rates along with their 
associated, exact 95% confidence intervals. 
9.3 
ADVERSE EVENTS FOR THE ANALYSIS OF THE PRIMARY AND 
SECONDARY OBJECTIVES 
9.3.1 
Adverse Events for the Analysis of Primary Objective 1 
If any of the following invasive actions occur in order to resolve an above listed insertion 
procedure AE, the AE will be included in the primary objective analysis: 
 Device removed 
 Device replaced 
 Device surgically repositioned 
 Other surgery performed related to the device or primary insertion procedure 
Subject deaths as a result of a BioMonitor 2 insertion procedure-related AE will be 
included in the primary objective analysis. Additionally, an AE that requires a transfer to 
a hospital facility during the initial in-office insertion procedure to resolve the AE will be 
included in the primary objective analysis. 
Primary objective 1 will exclude adverse events that do not meet these criteria. 
9.3.2 
Adverse Events for the Analysis of Secondary Objective 1 
All insertion procedure-related AEs excluded from primary objective 1 are included in 
secondary objective 1 analysis. 
9.4 
ADVERSE EVENT REPORTING 
The AEs that an IRB considers reportable are dependent on the particular IRB. To avoid 
underreporting, BIOTRONIK recommends that, at a minimum, the investigator reports 
insertion procedure-related and device-related AEs, as well as protocol-defined non-
procedure non-system related AEs, that occur during the BioInsight Study to 
BIOTRONIK and the IRB. 
The study site will report the AE on the Adverse Event eCRF. Additionally, study sites 
may report AEs through MedWatch, FDA’s adverse event reporting tool for market-
released devices. As defined in BIOTRONIK’s internal procedures, AEs may be 
reported by BIOTRONIK through manufacturer’s MedWatch reports. 

 
 
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10. OTHER GENERAL INFORMATION 
10.1 PROTOCOL COMPLIANCE 
The investigator is responsible for conducting the study in accordance with the signed 
agreement, the study protocol, applicable laws, and any conditions of approval imposed 
by the reviewing IRB. The investigator shall notify BIOTRONIK and the reviewing IRB in 
writing no later than 5 working days after any significant deviation from the study plan to 
protect the life or physical well-being of a subject in an emergency. Except in such 
emergency, prior approval by BIOTRONIK is required for significant deviations from the 
study plan.  
BIOTRONIK categorizes protocol noncompliance instances as either violations or 
deviations. Both protocol violations and deviations will be reported during interim 
reports. 
10.1.1 
Protocol Violations 
Protocol violations are defined as instances where the protocol requirements and/or 
regulatory guidelines were not followed, and are generally more serious in nature. 
Protocol violations are considered to potentially affect the scientific soundness of the 
plan and/or the rights, safety, or welfare of subjects. Protocol violations include, but are 
not limited to: 
 Failure to obtain consent 
 Subject inclusion/exclusion violations and protocol requirement violations that affect 
the primary objectives of the study design 
These violations will be reported in accordance with applicable regulatory timelines and 
the site must notify the reviewing IRB per the IRB’s reporting requirements. The site 
should provide a copy of the IRB protocol noncompliance notification (as applicable) to 
BIOTRONIK. Protocol violations must also be reported to BIOTRONIK via Protocol 
Noncompliance eCRFs. 
10.1.2 
Protocol Deviations 
Protocol deviations are deviations from the requirements of the protocol in such a 
manner whereby data is unusable or not available. Protocol deviations are less serious 
in nature. The site should report protocol deviations of required per the IRB of record. 
Protocol deviations include, but are not limited to: 
 Procedure not performed within the allowed follow-up window 
 Required data not obtained 
The site must report protocol deviations to BIOTRONIK via Protocol Noncompliance 
eCRFs. Both protocol deviations and violations will be reported in interim reports. 

 
 
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10.2 STUDY EXITS 
Once a subject is enrolled and successfully undergoes insertion, every effort should be 
made to continue to follow the subject in the study. However, it is inevitable that some 
subjects will decline to participate further, change geographic location, or become non-
compliant with the visit schedule.  
10.2.1 
Screen Failures 
Screen failures, as defined in Section 3.2.3, will be exited in the EDC system. The 
reason and date of withdrawal will be obtained and a Study Exit eCRF will be 
completed. 
10.2.2 
Unsuccessful Insertion Procedures 
Subjects with unsuccessful insertion procedures, as defined in Section 3.2.3, will be 
followed for 30 days post-insertion to capture any complications related to the insertion 
procedure and then will be exited. The reason and date of withdrawal will be obtained 
and a Study Exit eCRF will be completed.  
10.2.3 
Withdrawal of Consent  
If consent is withdrawn, the reason and date of withdrawal will be obtained and a Study 
Exit eCRF will be completed. 
10.2.4 
Subject Death  
In the event of subject death during study participation, personnel at the study site are 
asked to notify BIOTRONIK as soon as possible by completing a Study Exit eCRF. If 
subject death was associated with an adverse event, an Adverse Event eCRF will also 
be required.  
The following information should be reported for any subject death: 
 Subject records such as a death certificate, death report signed by the investigator, 
or other relevant medical records that include the following details: 
 Date of death 
 Place death occurred 
 Immediate cause of death 
 Statement whether death was device or insertion procedure-related 
Whenever possible, devices that are removed should be returned to BIOTRONIK for 
analysis. 

 
 
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10.2.5 
BioMonitor 2 Removal 
Any subject who has the BioMonitor 2 ICM removed during the follow-up will be 
withdrawn from the study. If the BioMonitor 2 is replaced with another BioMonitor 2, the 
subject will not continue participation in the study. A Study Exit and System Revision 
eCRF should only be completed after documentation of the device removal or 
replacement procedure is available (see Section 3.2.5).  
Whenever possible, devices that are removed must be returned to BIOTRONIK for 
analysis. 
10.2.6 
 Lost to Follow-up 
Subjects lost to follow-up are those for whom contact is lost despite the investigator’s 
best efforts to locate the subject. Study sites should attempt to contact these subjects in 
order to maintain study visit compliance and all contact attempts should be 
documented. At a minimum, the site should make and document two attempts to 
contact the subject by phone and one attempt by certified mail. 
In the event the subject cannot be contacted using the above methods, the subject 
should be exited from the study by completing a Study Exit eCRF. BIOTRONIK Home 
Monitoring® reports will be accepted for device data to support the secondary objectives 
in the event that the subject is lost to follow-up. 
10.2.7 
Study Participation Complete 
All subjects who undergo successful insertion procedures are expected to be followed 
for 90 days post-insertion (window -15, +30 days). After a subject completes their final 
routine visit in this time interval, their study participation is complete and the subject 
should be exited from the study by completing a Study Exit eCRF. 
10.3 INFORMED CONSENT 
Prior to the subject’s participation in the study, informed consent is required from all 
subjects. Informed consent should be obtained in accordance with the FDA regulations 
(21CFR, Part 50). The investigator is required to inform BIOTRONIK and the reviewing 
IRB within 5 days if any subject was not appropriately consented to participate in the 
study. In order to assist with the consent process, BIOTRONIK will provide a template 
subject consent form to study sites participating in the study. 
10.4 IRB APPROVAL 
IRB approval is required from each institution prior to participation in this post-market 
study. Subject enrollment may not begin until the IRB and BIOTRONIK have granted 
approval for the study site. IRB approval is also required throughout the duration of this 
clinical study. If IRB approval is withdrawn, BIOTRONIK must be notified within 5 
working days. 

 
 
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10.5 OTHER INSTITUTIONS AND PHYSICIANS 
This post-market study is not transferable to other institutions attended by the 
investigator unless prior approval is obtained from both BIOTRONIK and the 
appropriate IRB. Additional study sites may be included in this study but may not 
exceed the limits set by the protocol. Only approved investigators are authorized to 
participate in the study. However, there are certain situations where an investigator 
might not be immediately available to provide the necessary medical care for a subject 
enrolled in this study (e.g. when a subject goes to the emergency room for medical 
treatment). In these instances a protocol deviation will not be issued and all available 
data will be utilized. In any such situations, the IRB and the investigator must continue 
to provide oversight for that subject’s medical care and rights as a research subject. 

 
 
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11. RECORDS AND REPORTS 
11.1 INVESTIGATOR RECORDS 
Investigators are required to maintain on file the following accurate, complete and 
current records relating to this study: 
 All correspondence relating to the study with another investigator, an IRB, 
BIOTRONIK, a monitor, or the FDA, or any other regulatory authority. (e.g., a letter 
sent from the investigator to the IRB). 
 A copy of the study protocol 
 Signed investigator or research agreement 
 Signed Financial Disclosure Form 
 A copy of the IRB letter approving the research study 
 A copy of the IRB approved subject Informed Consent Form 
 All documentation, including: 
 a copy of the signed subject consent form 
 all supporting documentation for data entered into the EDC system 
 records of any adverse device effect, including supporting documentation 
 records pertaining to subject deaths during the study 
 documentation and rationale for any deviations from the clinical protocol 
 any other records required by BIOTRONIK 
 records of device disposition 
11.2 INVESTIGATOR REPORTS 
Investigators are required to prepare and submit to BIOTRONIK the following complete, 
accurate, and timely reports on this study when necessary: 
 Notification of a subject death during the study 
 Notification of the withdrawal of IRB approval 
 Annual progress reports prepared for the IRB 
 Notification of any deviations from the study plan 
 Notification that an informed consent was not obtained from the subject 
 Final summary report prepared for the IRB 
 Any other information upon the request of an IRB, FDA, or BIOTRONIK 

 
 
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Table 3 outlines the responsibilities, including time constraints, for submitting the above 
reports.  
Table 3: Investigator Reporting Responsibilities 
Type of Report 
Report to 
BIOTRONIK 
Report to IRB 
Time Constraints of Notification 
Subject Death During 
Study 
Required 
Required 
BIOTRONIK as soon as possible and as 
required by reviewing IRB 
Subject Withdrawal 
Required 
IRB 
Dependent 
Within 5 working days 
Withdrawal of IRB 
Approval 
Required 
Required 
Within 5 working days 
Progress Report 
Required 
Required 
Submitted not less often than yearly 
Significant Deviations from 
Protocol 
Required 
Required 
Within 5 working days after emergency 
to protect life or physical well-being of 
subject, otherwise prior approval by 
BIOTRONIK is required 
Informed Consent Not 
Obtained 
Required 
Required 
As soon as possible after discovery and 
no more than 5 working days 
11.3 SPONSOR RECORDS 
BIOTRONIK will maintain the following records: 
 All correspondence that pertains to the study with the investigator(s), IRB, and FDA 
 Investigator agreements, financial disclosures, and current curriculum vitae 
 Name and address of each investigator and each IRB that is involved with the study 
 Adverse events and complaints 
 Adverse device effects  
 Electronic Case Report Form data 
 Clinical study plan and report of prior investigations 
 Monitoring reports 
 Clinical progress reports 

 
 
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Table 4 outlines the responsibilities, including time constraints, for sponsor reports. 
Table 4: Sponsor Reporting Responsibilities 
Type of Report 
Prepared by 
BIOTRONIK for 
Time Constraints 
of Notification 
Withdrawal of IRB Approval 
All reviewing IRBs and 
participating investigators 
Notification within 5 working days of 
receipt of notice of withdrawal of 
approval 
Progress Report 
All reviewing IRBs 
A progress report will be submitted at 
least annually 
Recall and Disposition 
FDA, all reviewing IRBs 
Notification within 30 working days and 
will include the reasons for any request 
that an investigator return, repair or 
otherwise dispose of any devices. 
Final Report 
All reviewing IRBs and 
participating investigators 
Notification within 30 working days of 
the completion or termination of the 
study. A final report will be submitted 
within 6 months after completion or 
termination of the study. 

 
 
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12. REFERENCES 
[1] Pürerfellner H, et al. Miniaturized Reveal LINQ insertable cardiac monitoring system: 
First-in-human experience. Heart Rhythm 2015;12(6):1113-9. 
 
[2] Mittal S, et al. Safety Proﬁle of a Miniaturized Insertable Cardiac Monitor: Results 
from Two Prospective Trials. Pacing and Clinical Electrophysiology 2015;38(12):1464-9. 
 
[3] Pachulski R, et al. Implant Evaluation of an Insertable Cardiac Monitor Outside the 
Electrophysiology Lab Setting. PLoS ONE 2013;8(e71544):1-6. 
 
[4] Pakarien S, et al. Short-term implantation-related complications of cardiac rhythm 
management device therapy: a retrospective single-centre 1-year survey. Europace 
2010;5:907-25. 
 
[5] Poole JE, et al. Complication rates associated with pacemaker or implantable 
cardioverter-defibrillator generator replacements and upgrade procedures: results from 
the REPLACE registry. Circulation 2010; 122(16):1553-61. 
 
[6] Hancox JG, et al. The Safety of Office-Based Surgery:  
Review of Recent Literature From Several Disciplines. Arch Dermatology 2004; 
140(11):1379-82. 
 

 
 
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APPENDIX A: DEFINITION OF TERMS 
AE – Adverse Event 
AF – Atrial Fibrillation 
CEC – Clinical Events Committee 
CFR – Code of Federal Regulations  
Device Damage – Visible damage to the antenna or device body or mechanical 
malfunction that leads to the inability of the device to correctly sense the heart signals. 
Device Failure – Inability of the device to correctly sense the heart signals, not 
attributable 
to 
a 
mechanical 
malfunction 
that 
remains 
unresolved 
despite 
reprogramming and/or repositioning. 
Device Migration – Visual, radiographic, electrical or electrocardiographic evidence of 
device displacement from the original implant site or electrode displacement that 
adversely affects device performance or subject health. 
Device Protrusion – Device or antenna perforation through the skin that is not a result 
of skin erosion.  
Device Rejection Phenomena – Reaction to device materials; includes local tissue 
reaction and metal sensitivity. 
eCRF – Electronic Case Report Form 
EDC – Electronic Data Capture system 
Excessive Bleeding – Bleeding during the insertion procedure that cannot be stopped 
by applying pressure alone. 
FIT – Fast Insertion Tool 
Fluid Accumulation within the Device Pocket - Fluid swelling within the insertion site 
that is not related to infection or considered to be a hematoma, which requires surgical 
intervention to resolve. 
Hematoma – An accumulation or persistent swelling of blood that requires evacuation, 
drainage, post-insertion hospitalization, or blood transfusion. 
ICD – Implantable Cardioverter Defibrillator 
 
ICM – Insertable Cardiac Monitor 
IRB – Institutional Review Board 
IRL – Implantable Loop Recorders  
ITT – Intention-to-treat 
Non-healing Pocket Dehiscence – Separation of wound edges around the insertion 
site of the device that has not healed; excludes hematoma, seroma, infection, and 
erosion. 
NYHA – New York Heart Association 

 
 
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OAC – Oral Anticoagulant  
Pocket Pain – Pain greater than 1 week post-insertion requiring intervention with a 
narcotic (if narcotics are not already prescribed) or requiring pocket revision. 
Primary Infection – Infection requiring intervention such as IV antibiotics, device 
removal, or hospitalization. Excludes superficial infection that is resolved with outpatient 
antibiotics. 
sECG – Subcutaneous Electrocardiogram 
Skin Erosion – Deterioration of tissue over the implant site or the movement of the 
device or antenna through the skin. 
Secondary Infection – Infection that is determined not to be a result of the insertion 
procedure, but may be due to previous course of therapy or pre-existing infection. 
Superficial Infection – Infection that only involves the skin and surrounding 
subcutaneous tissue around the incision site of the insertion procedure that is treated on 
an outpatient basis or a stitch abscess that requires outpatient antibiotics.  
Surrounding tissue damage – Significant physical damage to the pocket or 
surrounding subcutaneous tissues as a result of insertion procedure.  
Suspected Device Failure – Device issue that is believed to be an electrical 
malfunction. 

 
 
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APPENDIX B: DETAILED PROCEDURES 
I. 
Insertion Visit Device Data 
R-Wave Amplitudes  
 Interrogate the BioMonitor 2 
 Freeze window to capture the R-waves as shown in Figure 11 using the “
” 
icon.  
Figure 11: Freeze Window 
 
 Provide the peak amplitudes of two R-waves using the calipers. Document 
the two R-wave amplitudes on a study worksheet or medical record. “Print” 
and “Store” this Freeze window (at least 25 mm/s). 
 While in the Freeze window with the R-waves selected, print a screenshot by 
following Figure 12. To do this, connect the USB flash drive (orange arrow) to 
the Programmer USB port. Open left paper tray (green arrow). Press the Stop 
and the 10 button (blue arrow). 
Figure 12: Print Screen Instructions 
 

 
 
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II. 
Wound Check Visit and 90-day Follow-up visit Device Data 
Please follow these steps when BIOTRONIK Home Monitoring® is not available.   
Average R-Wave Amplitude 
 Under “Diagnostics”  “Sensing”  “R-wave trend,” put the caliper on the 
date of visit, and record the value displayed above the graph with the date of 
visit selected.  
Figure 13: R-Wave Amplitude Trend 
 
 While in the R-Wave trend window with the date of visit selected, print a 
screenshot by following Figure 12. To do this, connect the USB flash drive 
(orange arrow) to the Programmer USB port. Open left paper tray (green 
arrow). Press the Stop and the 10 button (blue arrow). 
Average Noise Burden 
 Under “Diagnostics”  “Sensing”  “Noise duration trend,” put the caliper on 
the date of visit, and record the value displayed above the graph with the date 
of visit selected.  

 
 
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Figure 14: Noise Duration Trend 
 
 
 While in the Noise duration trend with the date of visit selected, print a 
screenshot by following Figure 12. To do this, connect the USB flash drive 
(orange arrow) to the Programmer USB port. Open left paper tray (green 
arrow). Press the Stop and the 10 button (blue arrow). 
III. 
90-day visit Device Data “Read out” 
Please follow these steps at the end of the 90-day visit.   
 Connect a USB flash drive to the Programmer 
 Apply the programming wand above the BioMonitor 2. 
 Download the data from the BioMonitor 2 memory while the subject is in a 
reclined position. Select “More”  “BioMonitor 2”  “Device Data”  “Read 
out”. The data transmission can take about 5 minutes.  

 
 
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Figure 15: Device Data Read Out 
 
 Open the “Data Manger” and select the correct subject and corresponding 
visit date.  
 Under “Options,” select “Backup” and “PDF” under the USB column as shown 
in Figure 16. Verify that “Backup” is selected; this is the only way to export the 
raw data with the follow-up information. Note that the automatic export option 
is not required. 
Figure 16: Export Options for data storage on USB stick 
 
 After closing the “Options” window, open “Preview” and select all follow-up 
data.  
 Close the “Preview” window and select “Export.”