Human Use Condition Study-Fluoroscopic Evaluation of 3D Curvature of Implanted Right Ventricular Leads in Humans
Conditions: Pacemaker Malfunction
Sponsor: Duke University

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Human Use Condition Study 
Version 3.0 January 5, 2021 
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Human Use Condition Study- 
Fluoroscopic Evaluation of 3D Curvature of Implanted 
Right Ventricular Leads in Humans 
SHORT TITLE: HUCS 
CLINICAL INVESTIGATION PLAN 
 Final Protocol Version 3.0 
January 5, 2021 
Sponsored By 
Duke Clinical Research Institute 
This protocol contains confidential information for use by the Investigators 
and their designated representatives participating in this clinical investigation. 
The protocol should be held confidential and maintained in a secure location. 
Do not copy or distribute without written permission from Duke Clinical Research 
Institute 

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Contact Information 
Role 
Contact  
Study Sponsor  
Jonathan Piccini, MD 
Duke Clinical Research Institute 
300 West Morgan Street 
Durham, NC 27701 
CIED Lead 
Manufacturers  and 
Funders of Study 
Abbott 
15900 Valley View Court 
Sylmar, CA 91342 
(818) 493-3147 
 
Medtronic CRHF  
8200 Coral Sea Street NE 
Mounds View, MN 55112  
(763) 526-8000 
 
Boston Scientific  
4100 Hamline Avenue North 
St. Paul MN 55112-5798 
(651) 582-4000 
 
Biotronik SE & Co. KG 
Woermannkehre 1 
12359 Berlin, Germany 
+49-30-68905-0 
 
BIOTRONIK, Inc. 
6024 Jean Road 
Lake Oswego, OR 97035 
(800) 547-0394 
AAMI Research 
Project Lead 
Timothy P. Quinn, PhD 
Technical Co-chair, AAMI Leads Working Group  
Mechanical Engineer, Fatigue and Fracture Group 
National Institute of Standards and Technology 
325 Broadway, MS 647.02 
Boulder, CO 80305 
Phone: (303) 497.3480 
E-mail: timothy.quinn@nist.gov 
 Vendor/Lab  
Timothy Quinn, Ph.D. 
National Institute of Standards and Technology 
325 S. Broadway 
Boulder, CO 80305 
Phone: (303) 497-3480 
E-mail: timothy.quinn@nist.gov 

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Human Use Condition Study (HUCS) 
 
PROTOCOL SIGNATURE PAGE 
 
 
The signature below constitutes the receipt and review of the HUCS 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 U.S. federal regulations, ICH and GCP guidelines. 
 
PRINCIPAL INVESTIGATOR: 
 
Signed: 
 
 
 
 
Name (please print) 
 
 
 
 
 
Signature 
 
Date 
 

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2. 
Protocol Synopsis 
Human Use Condition Study- 
Fluoroscopic Evaluation of 3D Curvature of Implanted 
Leads in Humans 
SHORT TITLE: HUCS 
Study Design 
and 
Objective(s) 
The AAMI Human Use Condition Study (HUCS) is a prospective, 
observational, multi-center clinical study intended to determine 
whether Right Ventricular (RV) lead curvature in vivo is a function 
of lead stiffness.  The results of this study will comprise a reference 
dataset to be used in a new international standard for conductor 
flexural fatigue performance of implantable CIED (Cardiac 
Implantable Electrical Device) RV leads.  
The HUCS study objectives are as follows: 
1. Measure dynamic in vivo curvature of RV pacing and 
defibrillator leads in the extravenous and intracardiac 
anatomy 
2. Measure the relationship between lead bending 
stiffness and in vivo curvature 
3. Assess the relationship between subject and implant 
variables and lead curvature 
Primary 
Endpoints 
Three primary endpoints will assess the relationship between lead 
stiffness and curvature – one endpoint each for three different 
regions of the lead.   
1. In vivo cyclic curvature and mean curvature of pacing and 
defibrillation leads in the extravenous region will be 
determined during specified arm movements.  
2. In vivo cyclic curvature and mean curvature of pacing and 
defibrillation leads in the intracardiac region will be 
determined during two or more cardiac cycles.  
3. In vivo cyclic curvature and mean curvature of pacing and 
defibrillation leads in the connector region will be 
determined during specified arm movements.  
The relationship between lead stiffness and curvature will be 
evaluated for all three Primary Endpoints. 
Subject 
Population 
The study will enroll at least 80 and up to 120 subjects with one 
of four different market-released lead families identified in the 
tables below. 

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The leads are from all four CIED manufacturers participating in 
this protocol. Approximately 30 leads from each manufacturer’s 
lead family will be required.  
ICD Leads of 
Interest  
Manufacturer 
Model(s) 
Description 
Abbott 
LDA 210Q 
 
LDA 220Q 
 
LDA 230Q 
Optisure 
Single 
Coil 
Defibrillation Lead 
Optisure 
Dual 
Coil 
Defibrillation Lead 
Optisure 
Dual 
Coil 
Defibrillation Lead 
Medtronic 
6935M Quattro Secure Single Coil 
Defibrillation Lead 
Pacing Leads 
of Interest 
Manufacturer 
Model(s) 
Description 
Biotronik 
Siello S, Solia S Active Fixation Leads 
Boston Scientific 
4452, 4453, 4456, 
4457 
FINELINE II/ FINELINE II 
Sterox 
Passive 
Fixation 
(polyurethane) 
Boston Scientific 
4463/4464/4465 
4469/4470/4471 
FINELINE II/ FINELINE II 
Sterox EZ Positive Fixation 
(polyurethane) 
 
Inclusion 
Criteria 
1. Patients with RV leads included in the scope of this study whose 
system has been implanted for at least 3 calendar months 
2. Patients at least 18 years of age and capable of providing 
informed consent 
3. Patients who can physically perform range of arm motion and 
breath-holding described in the imaging protocol (section 
11.1.1) 
4. Patients who are willing and able to comply with instruction 
related to the imaging protocol 
Exclusion 
Criteria 
1. Planned lead modification 
2. Patients with abandoned leads (includes: RV/RA/LV) 
3. Patients undergoing second or subsequent pulse generator 
change 
4. Patient has permanent atrial arrhythmias 
5. Limited life expectancy or medical condition that would not 
allow completion of the study 
6. Patient is known to be pregnant or breastfeeding at time of 
consent 
7. Limited range of mobility of the implant location arm 

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8. Patient is unable to climb on and off an examination table 
unassisted 
9. Patients deemed hemodynamically unstable 
Study 
Overview and 
Follow-up 
Schedule 
The study will consist of imaging sessions conducted at least 3 
months post-implant. The image data will be processed using 
custom 3D reconstruction software to produce data for lead 
curvature. Subject demographic information, disease state, 
implant technique details (access, implant site, etc.) will be 
collected. 
Enrollment → Acquire Imaging  
Study 
Duration 
Enrollment is expected to be completed in approximately 6 
months; therefore, the total study duration is estimated to be 
approximately 12 months. 
Subject 
Duration 
The study duration for each subject is expected to be 
approximately one month. 
Planned 
Number of 
Investigation
al Sites  
Up to 10 U.S. centers will participate 
 
 

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3. 
Table of Contents 
1. Title Page ...................................................................................... 1 
2. Protocol Synopsis ................................................................................ 4 
3. Table of Contents ................................................................................ 7 
3.1. Table of Figures ................................................................................... 10 
3.2. Table of Tables .................................................................................... 10 
4. Introduction ...................................................................................... 11 
4.1. Background ......................................................................................... 11 
4.2. Study Rationale ................................................................................... 14 
4.3. Overview of Data Acquisition and Analysis ............................................... 14 
 Determine Lead Stiffness ............................................................... 14 
 Acquire cine fluoroscopy data (DICOM files)...................................... 15 
 Perform 3-D reconstruction of Lead Trajectories ................................ 16 
5. Device Description ............................................................................. 16 
6. Required Imaging System ................................................................... 17 
7. Study Overview and Endpoints ............................................................ 17 
7.1. Study Overview ................................................................................... 17 
7.2. Primary Endpoints ................................................................................ 18 
 Primary Endpoint 1 (Extravenous Region) ........................................ 18 
 Primary Endpoint 2 (Intracardiac Region) ......................................... 19 
 Primary Endpoint 3 (Connector Region) ............................................ 21 
7.3. Sample Size ........................................................................................ 23 
7.4. Additional Analyses .............................................................................. 23 
 Multiple Measures per Region.......................................................... 23 
 Interaction Analyses ...................................................................... 23 
 Multivariable Analyses.................................................................... 24 
7.5. Changes to Planned Analyses ................................................................. 24 
7.6. Handling of Missing, Unused, or Spurious Data ........................................ 24 
8. Study Design .................................................................................... 25 
8.1. Data Flow ............................................................................................ 26 
 Data Collected by Center ................................................................ 27 
 Data Sent to DCRI ......................................................................... 27 
 Data Sent to NIST ......................................................................... 28 
 Data Transfer from NIST to Lead Manufacturers ................................ 28 

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 3-D Reconstruction of Lead Trajectories ........................................... 28 
8.2. Scale and Duration ............................................................................... 28 
8.3. Justification for the Study Design ........................................................... 28 
9. Subject Selection ............................................................................... 29 
9.1. Study Population and Eligibility .............................................................. 29 
9.2. Inclusion Criteria .................................................................................. 29 
9.3. Exclusion Criteria ................................................................................. 29 
10. Subject Accountability ........................................................................ 30 
10.1. 
Point of Enrollment .......................................................................... 30 
10.2. 
Withdrawal ..................................................................................... 30 
11. Study Methods .................................................................................. 30 
11.1. 
Data Collection ............................................................................... 30 
 Imaging Protocol ........................................................................... 32 
11.2. 
Imaging Data recorded .................................................................... 34 
11.3. 
Informed Consent ........................................................................... 35 
11.4. 
Source Documents .......................................................................... 35 
12. Data Management ............................................................................. 35 
12.1. 
Data Collection, Processing, and Review ............................................. 35 
12.2. 
Data Retention ................................................................................ 36 
12.3. 
External Laboratories ....................................................................... 36 
13. Deviations ........................................................................................ 37 
14. Compliance ....................................................................................... 37 
14.1. 
Statement of Compliance ................................................................. 37 
14.2. 
Investigator Responsibilities ............................................................. 37 
 Delegation of Responsibility ............................................................ 39 
14.3. 
Institutional Review Board ................................................................ 39 
14.4. 
Sponsor Responsibilities ................................................................... 39 
15. Monitoring ........................................................................................ 39 
16. Potential Risks and Benefits ................................................................ 40 
16.1. 
Anticipated Adverse Events .............................................................. 40 
16.2. 
Risks Associated with Participation in the Clinical Study ....................... 40 
 Radiation Exposure ........................................................................ 40 
16.3. 
Risk Minimization ............................................................................ 41 
16.4. 
Anticipated Benefits ......................................................................... 42 
16.5. 
Risk to Benefit Rationale .................................................................. 42 

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17. Adverse Event Reporting .................................................................... 42 
17.1. 
Reportable Events by investigational site to DCRI ................................ 42 
17.2. 
Definitions ...................................................................................... 43 
 Adverse Event Definitions ............................................................... 43 
17.3. 
Relationship to Study Procedure ........................................................ 43 
17.4. 
Adverse Event Reporting to DCRI ...................................................... 45 
17.5. 
Investigator Reporting Requirements ................................................. 46 
17.6. 
Reporting Responsibilities to IRB ....................................................... 47 
17.7. 
DCRI Records and Reports................................................................ 47 
18. Additional Study Conditions................................................................. 48 
18.1. 
Informed Consent ........................................................................... 48 
18.2. 
Termination of Study Participation by the Investigator or Withdrawal of IRB 
Approval .................................................................................................... 49 
18.3. 
Requirements for Documentation and Subject Follow-up ...................... 49 
18.4. 
Criteria for Suspending/Terminating a Study Site ................................ 50 
19. Publication Policy ............................................................................... 50 
20. Abbreviations and Definitions .............................................................. 51 
20.1. 
Abbreviations .................................................................................. 51 
 
 

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3.1. 
Table of Figures 
Figure 1: S-N Plot .......................................................................................... 12 
Figure 2: S-N Plot for Boston Scientific Defibrillation Lead . ................................. 13 
Figure 3: Example Plot – Stiffness in Intracardiac Region .................................... 15 
Figure 4: Example Plot – Stiffness in Connector and Extravenous Regions ............. 15 
Figure 5: Cine Fluoroscopy Example ................................................................. 16 
Figure 6: Curvature and Stiffness Values used Primary Endpoint 1 Analyses .......... 19 
Figure 7: Curvature and Stiffness Values used Primary Endpoint 2 Analyses .......... 21 
Figure 8: Curvature and Stiffness Values used Primary Endpoint 3 Analyses .......... 22 
Figure 9: Study Flowchart ............................................................................... 26 
Figure 10: Data Flow ...................................................................................... 27 
Figure 11: Illustrations of prescribed arm positions............................................. 34 
 
 
 
3.2. 
Table of Tables 
Table 1: RV Pacing Leads ................................................................................ 16 
Table 2: Defibrillation Leads ............................................................................ 17 
Table 3: Inclusion Criteria ............................................................................... 29 
Table 4: Exclusion Criteria ............................................................................... 30 
Table 5: Study Data Collection ......................................................................... 31 
Table 6: Source Documentation Requirements ................................................... 35 
Table 7: Potential Adverse Events .................................................................... 40 
Table 8: Criteria for Assessing Relationship of Study Procedure to Adverse Event ... 44 
Table 9: Communication requirements for reporting toDCRI ................................ 46 
Table 10: Additional Investigator Reporting Responsibilities ................................. 46 
Table 11: DCRI Sponsor Reporting Responsibilities ............................................. 48 
 
 
 
 
 
 

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4. 
Introduction 
4.1. 
Background 
The implantable leads are the only elements of the implantable cardioverter-
defibrillator (ICD) system that are meant to last the life of the patient without 
repair or replacement.  However, survival of ICD leads may be as low as 85% 
after 5 years and 60% after 8 years.1  Like all engineered systems, implantable 
leads are subject to degradation and possible failure from the effects of stresses 
imposed by the use environment.  Conductor fracture caused by metal fatigue is 
one of the more serious and common failure mechanisms for transvenous ICD 
leads.   
Fatigue life can be quantified in bench tests based on the stress-life method. In 
fatigue testing of ICD leads and in the in vivo use condition, conductor stress,, 
is proportional to curvature (C) and alternating stress, S, is proportional to cyclic 
(alternating) curvature (C).  For this reason, alternating stress, S, in lead fatigue 
studies is customarily reported as cyclic curvature with units of cm-1 or inch-1.   
To develop physiologically relevant bench tests for conductor fatigue performance 
of ICD and pacing leads, valid data on in vivo lead motion is needed - specifically 
cyclic curvature (C) in the intracardiac, extravenous, and connector regions.  
Preliminary studies have demonstrated the feasibility of acquiring these data by 
3D reconstruction of bi-plane cine fluoroscopy images.2 3 4   However, these studies 
were not randomized and did not control for effects of lead routing from the pulse 
generator implant site to the venous access site.  None were powered to provide 
sufficient data for the purpose defined for the present study.            
The stress-life (commonly denoted “S-N” in the literature on fatigue failure of 
materials) method was the first approach used to understand and quantify metal 
fatigue.  It has been the standard design method for almost 100 years.  The S-N 
approach is still widely used in design applications where applied stress is 
primarily within the elastic range of the material and the resultant lives (cycles to 
failure) are long, such as power transmission shafts.5 
 
1  
Kleemann et al, Circulation 2007;115:2474-2480 
2  
W Baxter, N Skadsberg, et. al., New Unanticipated Insights on Peak Lead Bending During Pectoralis Flexure. 
HRS 2010 
3  
Pau, W Baxter, et. al., Lead Use Conditions Imaging: A Noninvasive Upper Thoracic and Intracardiac Lead 
Mechanics Investigation, CARDIOSTIM, June2014   
4  
Hoffmann KR, Williams BB, Esthappan J, Chen SY, Carroll JD, Harauchi H, Doerr V, Kay GN, Eberhardt A, 
Overland M:  Determination of 3D positions of pacemaker leads from biplane angiographic sequences.  Med 
Phys 24:1854-1862, 1997 
5  
Bannantine, Julie, Fundamentals of Metal Fatigue Analysis. Upper Saddle River, New Jersey, U.S.A, Prentice-
Hall, Inc., 1990  

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The basis of the stress-life method is the Wöhler or S-N diagram, which is a plot 
of alternating stress, S, versus cycles to failure, N.  Alternating stress is defined 
as half of the cyclic stress range, or 0.5  (maximum stress – minimum stress).  
Figure 1 is an example of an S-N diagram for steel, plotting alternating stress 
against cycles to failure on logarithmic scales for both quantities.6 
Figure 1: S-N Plot 
 
Figure 2 shows an example of S-N data for a Boston Scientific defibrillation lead.  
A 2-cm section of the lead body was repeatedly bent between high and low 
curvature values for up to 20 million cycles, and the cathode conductor coil was 
monitored to determine at what cycle of bending the coil fractured.  Circles 
indicate test specimens which experienced coil fracture; crosses indicate 
specimens in which no coil fracture occurred during the test.7  Fatigue models 
based on cyclic curvature have been used successfully to model in vivo lead 
survival with respect to fatigue fracture in the Medtronic Sprint Quattro and Sprint 
Fidelis ICD leads.8 
 
6  
Shigley, Mechanical Engineering Design, New York, New York, U.S.A., McGraw-Hill Book Company, Third 
Edition,1977 
7  
D Smith, AAMI_PC_WG1_N213_ . Preliminary Fatigue Testing at Boston Scientific, AAMI CRMD Committee 
PC/WG1, Transvenous Cardiac Leads Working Group, 08-Apr-2014 
8  
T Haddad, A Himes and M Campbell. Fracture Prediction of Cardiac Lead Medical Devices Using Bayesian 
Networks. Reliability Engineering and System Safety.123(2014).  p145–157. 

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Figure 2: S-N Plot for Boston Scientific Defibrillation Lead.   
(Circles indicate test specimens which experienced coil fracture; crosses indicate specimens in 
which no coil fracture occurred during the test.) 
 
The current ISO standard for fatigue performance9 of transvenous defibrillation 
leads has proven to be insufficiently sensitive, since certain leads that met the 
ISO standard demonstrated poor reliability performance in service10 and were 
ultimately withdrawn from use.   
One limitation of the current standard is that it does not account for effects of use 
stresses on fatigue life.  In general, reliability of a population of apparently similar 
devices is affected by both variability in the strength of the device and variability 
in the stresses imposed on the device.  The stress-strength theory of reliability11 
accounts for both aspects.  A statistical method for quantifying lead fatigue life 
utilizing the stress-strength theory of reliability and Bayesian network analysis 
has been proposed12 and is currently under consideration for an improved standard 
for lead fatigue performance.13   
The Association for Advancement of Medical Instrumentation (AAMI) Cardiac 
Rhythm Management Device (CRMD) Committee is the organization responsible 
for developing standards for CIEDs.  The AAMI CRMD Committee, through their 
Leads Working Group (WG1), is responsible for developing a new fatigue standard 
based on the Bayesian network analysis method.14   
 
 
9  
ISO 14708-6, Implants for surgery — Active implantable medical devices — Part 6: Particular requirements 
for active implantable medical devices intended to treat tachyarrhythmia (including implantable 
defibrillators), 2008 
10  
R G Hauser, W H Maisel, et.al., Longevity of Sprint Fidelis Implantable Cardioverter-Defibrillator Leads and 
Risk Factors for Failure - Implications for Patient Management, Circulation, 123:  358-363, 2010 
11  
Kotz, S., Lumelskii, Y, and Pensky, M. (2003) The Stress-Strength Model and Its Generalizations: Theory 
and Applications, World Scientific Publishing Co. Pte. Ltd. Singapore 
12  
T.Haddad, et.al, Fracture Prediction of Cardiac Lead Medical Devices Using Bayesian Networks, Reliability 
Engineering and System Safety, 123(2014) 145–157 
13  
AAMI_PC_WG1_N169 Outline of Requirements for Fatigue Performance of Cardiac Rhythm Management 
Leads 
14   Cooke D, Himes A, Swerdlow C. Improved engineering standards for transvenous cardiac leads: A progress 
report from the Association for the Advancement of Medical Instrumentation Cardiac Rhythm Management 
Device Committee Leads Working Group, Heart Rhythm Journal, 2019; 16: 958–959 

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4.2. 
Study Rationale 
The purpose of this study is to obtain in vivo data for the dynamic flexing 
experienced by defibrillation and RV pacing leads in humans. This data will be 
used to develop an improved international standard method for evaluating fatigue 
performance. 
The current ISO standard for fatigue performance of transvenous defibrillation 
leads is insufficiently sensitive, since certain leads that met this standard have 
demonstrated poor reliability and were ultimately withdrawn from use. A limitation 
of the current standard is that it does not account for stresses due to the in vivo 
environment.  
The AAMI Cardiac Rhythm Management Committee Transvenous Cardiac Leads 
Working Group has developed a new methodology based on a combination of 
bench testing and in vivo lead curvature data. This method requires data from 
multiple defibrillator and pacing lead models. 
The proposed study will produce the data needed to complete the development of 
the new standard fatigue test methodology.  
4.3. 
Overview of Data Acquisition and Analysis 
 
Determine Lead Stiffness 
The funding CIED lead manufacturers will determine lead stiffness for the pacing 
and defibrillator leads included in this study in accordance with pre-defined 
requirements. (AAMI_PC_WG1_N169 Outline of Requirements for Fatigue 
Performance of Cardiac Rhythm Management Leads). Examples of these 
measurements are shown in Figure 3, and Figure 4. 

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Figure 3: Example Plot – Stiffness in Intracardiac Region 
 
 
Arrows indicate maximum value for C and corresponding stiffness for the intracardiac region. 
 
Figure 4: Example Plot – Stiffness in Connector and Extravenous Regions 
 
 
Arrows indicate maximum value for C and corresponding stiffness for the intracardiac region. 
 
 
Acquire cine fluoroscopy data (DICOM files)  
For each subject, cine fluoroscopy data (DICOM files) shown in Figure 5, for the 
pacing or defibrillator leads will be acquired for 3 regions– the intracardiac region, 
extravenous region, and connector region.  The intracardiac region will be imaged 
for two or more cardiac cycles; the extravenous region and connector regions will 
be imaged while the subject executes prescribed arm motions. 

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Figure 5: Cine Fluoroscopy Example 
 
 
Perform 3-D reconstruction of Lead Trajectories 
For each subject, cine fluoroscopy data (DICOM file) for the RV pacing or 
defibrillator lead will be reconstructed to generate 3D trajectories in time and 
spacing in accordance with the method described in AAMI_PC_WG1_N726 
Methodology for 3-D Reconstruction of Lead Trajectories from Bi-Plane 
Fluoroscopy DICOMs. An example of a 3-D lead trajectory is shown in Figure 5.  
For each lead, the maximum cyclic curvature, Cmax, and the corresponding 
value of lead stiffness will be determined by the lead manufacturer, for each region 
(intracardiac region, extravenous region, and connector region). 
5. 
Device Description 
The devices in this study are FDA approved, commercially available, Pacemaker 
(PM) systems and implantable cardioverter defibrillator (ICD) systems.   
Pacemaker systems are composed of any approved, commercially available dual 
chamber or single chamber pacemaker and at least one implantable pacing lead 
implanted in the right ventricle.  The pacing leads included in this study are listed 
in Table 1.  
Table 1: RV Pacing Leads 
 
Manufacturer 
Model(s) 
Description 
Biotronik 
Siello S, Solia S 
Active Fixation Leads 
Boston 
Scientific 
4452, 4453, 4456, 
4457 
FINELINE II/FINELINE II Sterox Passive 
Fixation (polyurethane) 
Boston 
Scientific 
4463, 4464, 4465, 
4469, 4470, 4471 
FINELINE II/FINELINE II Sterox EZ Positive 
Fixation (polyurethane) 
 
ICD systems are composed of any approved, commercially available dual chamber 
or single chamber ICD and at least one implantable defibrillation lead implanted 
in the right ventricle.  The defibrillation leads included in this study are listed in 
Table 2. 
 

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Table 2: Defibrillation Leads 
 
Manufacturer 
Model(s) 
Description 
Abbott 
LDA 210Q 
LDA 220Q 
LDA 230Q 
Optisure Single Coil Defibrillation Lead 
Optisure Dual Coil Defibrillation Lead 
Optisure Dual Coil Defibrillation Lead 
Medtronic 
6935M 
Quattro Secure Single Coil Defibrillation 
Lead 
6. 
Required Imaging System 
Center selection criteria include access to a biplane fluoroscopy system with 
capability of at least 15 frames per second (fps) and image portability using 
removable media or secure network. The following equipment must be available 
at each study site to support study activities; 
• 
Biplane fluoroscopy system with: 
o capability of fluoroscopy (scout image) capture at 7.5 fps or less and 
Cine recording at 15 fps or more 
o capability of image recording in a DICOM format 
o if available, capability of simultaneous recording of the ECG signal as 
part of the DICOM header 
• 
Secured Hard Drive for data storage and capabilities of nightly backup 
• 
Computer system capable of high-speed network data transfer 
7. 
Study Overview and Endpoints 
7.1. 
Study Overview 
The Human Use Condition Study (HUCS) is a prospective, observational, multi-
center clinical study intended to determine whether lead curvature in vivo is a 
function of lead stiffness.  The results of this study will comprise a reference 
dataset to be used in a new international standard for conductor flexural fatigue 
performance of implantable CIED leads.  
The extravenous region and connector region for each subject enrolled in the 
study will be imaged by high resolution, bi-plane cine fluoroscopy while the subject 
executes prescribed arm motions.  The intracardiac region will be imaged for two 
or more cardiac cycles. 
Lead trajectories in DICOM file images will be manually identified in both views.  
For each frame, 3D lead trajectory will be generated using indicated 2D lead 
trajectories. Three dimensional reconstructions will be generated for the 
prescribed arm motions utilized in the imaging study.   

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7.2. 
Primary Endpoints 
Three primary endpoints will assess the relationship between lead stiffness and 
curvature – one endpoint each for three different regions of the lead.  Primary 
Endpoint 1 will evaluate the extravenous region.  Primary Endpoint 2 will evaluate 
the intracardiac region.  Primary Endpoint 3 will evaluate the connector region.  
Failure to reject any of the null hypotheses does not indicate a failure of the study, 
but rather that no significant relationship between lead stiffness and lead 
curvature was observed. The results of the endpoint analyses will be used to 
inform the new lead standard.  
 
 
Primary Endpoint 1 (Extravenous Region) 
In vivo cyclic curvature (C) and mean curvature (Cmean) of RV pacing and 
defibrillation leads in the extravenous region will be determined during specified 
arm movements.  The relationship between lead stiffness and curvature will be 
evaluated.   
7.2.1.1. 
Hypotheses 
The following set of hypotheses will be used to evaluate the relationship between 
lead stiffness and curvature in the extravenous region: 
H0: a ≥ 0 
Ha: a < 0  
where a represents the coefficient for stiffness in the following model:  
log (curvature) = a*stiffness + b + normally distributed error. 
Prior studies of in-vivo curvature have shown that a lognormal distribution models 
the data well. The alternative hypothesis represents an inverse relationship 
between lead stiffness and curvature. 
7.2.1.2. 
Statistical Methods 
Each lead with lead stiffness and curvature data available in the extravenous 
region of the lead will be included in the analysis of Primary Endpoint 1.  Each 
lead’s curvature measurement used in the analysis will represent the maximum 
value of the curvature observed in the extravenous region.  Each lead’s stiffness 
measurement used in the analysis will represent the stiffness measurement at the 
location corresponding to the maximum value of the curvature (Figure 6). 

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Figure 6: Curvature and Stiffness Values used Primary Endpoint 1 
Analyses 
 
 
 
Arrows indicate maximum value for C and corresponding stiffness for the extracardiac region. 
The relationship between curvature and stiffness will be evaluated via a general 
linear model, treating log (curvature) as the outcome and stiffness as the 
predictor.  The following model will be fit: log (curvature) = a*stiffness + b + 
normally distributed error.  The 90% upper confidence limit of the coefficient for 
stiffness, a, will be compared to 0.  If the upper confidence limit is less than 0, 
the null hypothesis will be rejected, thereby establishing a significant relationship 
between curvature and stiffness in the extravenous region. 
 
Primary Endpoint 2 (Intracardiac Region) 
In vivo cyclic curvature (C) and mean curvature (Cmean) of RV pacing and 
defibrillation leads in the intracardiac region will be determined during two or more 
cardiac cycles. The relationship between lead stiffness and curvature will be 
evaluated.   
7.2.2.1. 
Hypotheses 
The following set of hypotheses will be used to evaluate the relationship between 
lead stiffness and curvature in the intracardiac region: 
H0: a ≥ 0 

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Ha: a < 0 
where a represents the coefficient for stiffness in the following model:  
log (curvature) = a*stiffness + b + normally distributed error. 
Prior studies of in-vivo curvature have shown that a lognormal distribution models 
the data well. The alternative hypothesis represents an inverse relationship 
between lead stiffness and curvature. 
7.2.2.2. 
Statistical Methods 
Each lead with lead stiffness and curvature data available in the intracardiac 
region of the lead will be included in the analysis of Primary Endpoint 2.  Each 
lead’s curvature measurement used in the analysis will represent the maximum 
value of the curvature observed in the intracardiac region.  Each lead’s stiffness 
measurement used in the analysis will represent the stiffness measurement at the 
location corresponding to the maximum value of the curvature 
Figure 7). 

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Figure 7: Curvature and Stiffness Values used Primary Endpoint 2 
Analyses 
 
 
Arrows indicate maximum value for C and corresponding stiffness for the intracardiac region. 
The relationship between curvature and stiffness will be evaluated via a general 
linear model, treating log (curvature) as the outcome and stiffness as the 
predictor.  The following model will be fit: log (curvature) = a*stiffness + b + 
normally distributed error.  The 90% upper confidence limit of the coefficient for 
stiffness, a, will be compared to 0.  If the upper confidence limit is less than 0, 
the null hypothesis will be rejected, thereby establishing a significant relationship 
between curvature and stiffness in the intracardiac region. 
 
Primary Endpoint 3 (Connector Region) 
In vivo cyclic curvature (C) and mean curvature (Cmean) of RV pacing and 
defibrillation leads in the connector region will be determined during specified arm 
movements.  The relationship between lead stiffness and curvature will be 
evaluated.   
7.2.3.1. 
Hypotheses 
The following set of hypotheses will be used to evaluate the relationship between 
lead stiffness and curvature in the connector region: 
H0: a ≥ 0 
Ha: a < 0 

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where a represents the coefficient for stiffness in the following model:  
log (curvature) = a*stiffness + b + normally distributed error. 
Prior studies of in-vivo curvature have shown that a lognormal distribution models 
the data well. The alternative hypothesis represents an inverse relationship 
between lead stiffness and curvature. 
7.2.3.2. 
Statistical Methods 
Each lead with lead stiffness and curvature data available in the connector region 
of the lead will be included in the analysis of Primary Endpoint 3.  Each lead’s 
curvature measurement used in the analysis will represent the maximum value of 
the curvature observed in the connector region.  Each lead’s stiffness 
measurement used in the analysis will represent the stiffness measurement at the 
location corresponding to the maximum value of the curvature (Figure 8). 
Figure 8: Curvature and Stiffness Values used Primary Endpoint 3 
Analyses 
 
 
 
Arrows indicate maximum value for C and corresponding stiffness for the connector 
The relationship between curvature and stiffness will be evaluated via a general 
linear model, treating log (curvature) as the outcome and stiffness as the 
predictor.  The following model will be fit: log (curvature) = a*stiffness + b + 
normally distributed error.  The 90% upper confidence limit of the coefficient for 
stiffness, a, will be compared to 0.  If the upper confidence limit is less than 0, 
the null hypothesis will be rejected, thereby establishing a significant relationship 
between curvature and stiffness in the connector region. 

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7.3. 
Sample Size 
To sufficiently power each of the three Primary Endpoints, a total of 30 subjects 
enrolled for each manufacturer’s lead families is expected to yield at least 20 leads 
with usable endpoint data in the each of the 3 image regions.  Monte Carlo 
simulations were performed to establish the sample size, using the following 
assumptions: 
• 
Expected value for coefficient a = -0.23 
• 
Alpha (one-sided) = 10% (corresponding to a one-sided 90% upper 
confidence limit) 
• 
Power = 99% 
• 
Missing data = 33% 
Reasons for missing data includes, imaging and/or ECG data not collected, 
imaging data not optimal for analysis, and subject withdrawal/death. Enrollment 
may stop prior to 30 subjects if 20 useable data sets have been collected.  
7.4. 
Additional Analyses 
 
Multiple Measures per Region 
In addition to the Primary Endpoint analyses, in which only one measurement per 
region will be assessed, analyses evaluating multiple measurements per region 
will be performed.  Curvature and stiffness measurements obtained in millimeter 
intervals will be evaluated.  Analyses will be performed separately for each of the 
three regions of the lead.  To account for the within-subject correlation, a random 
effects general linear model will be used.  These analyses will evaluate the 
relationship between curvature and stiffness across the entire region of the lead. 
 
Interaction Analyses 
Each of the three Primary Endpoints will be assessed for its association with 
various lead, procedural and subject characteristics.  The interaction between 
each characteristic and stiffness will be assessed using a general linear model.  
Each characteristic will be assessed separately.  The list of characteristics includes, 
but is not limited to: 
Product Level Characteristics  
• 
Model/serial of pulse generator and leads 
• 
Lead related information: 
o Septal / apical positioning of lead 
 
o Active / passive fixation  
 
 
o Dual / single coil defibrillator lead  
o Manufacturer 
o Implant date(s) of leads 
• 
Pulse generator information: 
o Implant date of pulse generator 

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o Manufacturer 
o Pulse generator position 
Implant Procedure Related Characteristics 
• 
Access technique (axillary, cephalic, subclavian intra-thoracic, subclavian 
extra-thoracic) 
• 
Lead configuration determined from retrospective AP/PA Chest X-rays 
collected post implant  
Subject Level Characteristics 
• 
Subject birth date, gender, race, ethnicity, height, weight  
 
 
• 
Ejection fraction, implant indication 
  
 
Multivariable Analyses 
The association between curvature and stiffness will be evaluated in the presence 
of other potential confounding variables, including but not limited to the 
characteristics listed above.  A multivariable general linear model for each 
endpoint will be analyzed, treating curvature as the outcome and stiffness and 
other characteristics as the predictors.  To minimize the potential for overfitting 
the multivariable model, a subset of characteristics will be included in the model.  
To select which characteristics are included in the multivariable model, each 
characteristic’s association with curvature will be assessed via a univariable 
model.  Characteristics significantly associated with curvature in the univariable 
models will be included in the multivariable model.  A separate multivariable 
model will be analyzed for each endpoint.  
7.5. 
Changes to Planned Analyses 
Any changes to the planned statistical analyses outlined in this protocol will be 
documented in the statistical analysis plan and/ or clinical study reports along with 
a reason for the deviation. 
7.6. 
Handling of Missing, Unused, or Spurious Data  
The respective centers will be contacted by Duke Clinical Research Institute 
(DCRI) to remedy any missing, unused, or spurious data in the case report forms 
(CRFs). In case of missing imaging/ECG data, the respective centers will confirm 
the availability of the data. If parts of the imaging/ECG data are missing or 
spurious, the analysis of the data set may be excluded, if the missing or spurious 
data prevents appropriate analysis of the data set. 

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8. 
Study Design 
HUCS is a prospective, observational, multi-centre clinical study.  A previous 
publication hypothesized that, in the extravenous region, curvature in vivo is a 
function of lead stiffness. 15  The present study is intended to determine whether 
this phenomenon is evident in the intracardiac region and connector region as well 
as the extravenous region, and for leads having a wider range of stiffness. 
 
15 W Baxter, N Skadsberg, et. al., New Unanticipated Insights on Peak Lead Bending During Pectoralis Flexure. HRS 2010 

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Figure 9: Study Flowchart  
Pre-screen patients for applicable RV pacing or defibrillator leads listed in: 
Table 1 or Table 2 and assess study inclusion/exclusion criteria 
↓ 
DCRI staff to determine if specific lead manufacturer limit has been met (30 RV leads 
from each of the 4 manufacturers) 
↓ 
Informed Consent Obtained 
• 
Study inclusion/exclusion criteria verified 
↓ 
Enrollment Data Collection 
• 
Subject demographic and background medical information collected 
↓ 
Determine Timing of Image Acquisition and Schedule  
Note: If a subject is scheduled for a pulse generator change out, the images must be collected prior to 
the procedure 
 ↓ 
Image Acquisition 
• 
Collect Biplane Fluoroscopic Images per Section 11.1.1 
• 
Assess for adverse events due to imaging protocol 
• 
Transmit/Ship DICOM images to DCRI 
 
8.1. 
Data Flow 
The data collected by the implanting centers will be transferred to DCRI, NIST, 
and lead manufacturers as shown in the flowchart below (Figure 10).  

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Figure 10: Data Flow 
 
 
Data Collected by Center 
All subjects will be imaged by high-resolution bi-plane fluoroscopy in the intra-
cardiac region through 2 or more cardiac cycles, and in the extravenous region 
while the performing prescribed arm motions. NOTE: All imaging must be de-
identified prior to saving to the DICOM media.  All Media must be labeled clearly 
on the outside with the subject identifier.   Case Report Form data will be entered 
by the site staff into an electronic data capture system (EDC). 
 
Data Sent to DCRI 
The imaging media will be sent to DCRI via pre-specified shipping/transfer method 
and receipt verified. Enrollment data specified in section 7.4 will be provided to 
DCRI for review through entry in the EDC. Case report form data will be reviewed 
for completion and quality.  
Data Collected at Center 
Data to DCRI for eCRF 
review and image media 
receipt 
Data to CIED lead 
manufacturers for 3-D 
image reconstruction 
Data sent to NIST for 
Distribution  
3-D image reconstruction 
to NIST for Statistical 
Analysis and Final Report 

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Data Sent to NIST 
The images and de-identified subject data (see section 7.4) are transferred to 
NIST by DCRI. Data will include identification of the lead design, eCRF data and 
the DICOM media. 
 
Data Transfer from NIST to Lead Manufacturers 
NIST will transfer a copy of the DICOM file and subject data to the individual lead 
manufacturers 
for 
datasets 
containing 
their 
respective 
leads 
for 
3-D 
reconstruction. Each DICOM file will be reconstructed two times, once by the 
individual lead manufacturer, and a second time by one of the other lead 
manufacturers. 
 
3-D Reconstruction of Lead Trajectories  
Each lead manufacturer will perform 3-D reconstruction of the lead trajectories 
per the 3-D reconstruction protocols (AAMI_PC_WG1_N726 Methodology for 3-D 
Reconstruction of Lead Trajectories from Bi-Plane Fluoroscopy DICOMs). 
3-D reconstruction will be sent to NIST for statistical analyses and reporting per 
the statistical analyses plan (AAMI_PC_WG1_N725 HUCS Statistical Analysis 
Plan). 
8.2. 
Scale and Duration 
The HUCS study will enroll at least 80 and up to 120 subjects, with at least 20 
and up to approximately 30 subjects per lead family specified in Section 5. 
Enrollment is expected to be completed in approximately 6 months; therefore, the 
total study duration is estimated to be approximately 12 months. The study 
duration for each subject is expected to be approximately 1 month to account for 
time from enrollment to completing the imaging protocol.  Subject participation 
will be considered complete after image has been acquired.   Up to 10 U.S. centers 
will participate. 
8.3. 
Justification for the Study Design 
The purpose of this study is to improve the safety profile of transvenous leads, 
through the development of a new lead safety requirements standard. The data 
collected in this study is required for the development of the standard. 
Furthermore, the study poses no significant risks to the participants of the study. 

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9. 
Subject Selection  
9.1. 
Study Population and Eligibility  
At least 80 and up to 120 subjects will be enrolled based on their willingness, and 
consent to participate in this study, at centers with approved bi-plane fluoroscopy 
capabilities.  Subjects may be either male, or female, and must meet all of the 
inclusion criteria in Table 3 and none of the exclusion criteria in Table 4. 
9.2. 
Inclusion Criteria 
Subjects who meet all of the following criteria (see Table 3) may be given 
consideration for inclusion in this clinical investigation, provided no exclusion 
criterion (see Table 4) is met.  
Table 3: Inclusion Criteria 
Inclusion 
Criteria 
1. Patients with RV leads included in the scope of this study whose system 
has been implanted for at least 3 calendar months.  
2. Patients at least 18 years of age and capable of providing informed 
consent 
3. Patients who can physically perform range of arm motion and breath-
holding described in the imaging protocol (section 11.1.1) 
4. Patients are willing and able to comply with instruction related to 
imaging protocol 
9.3. 
Exclusion Criteria 
Subjects who meet any one of the following criteria (Table 4) cannot be included 
in this study or will be excluded from this clinical study. 

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Table 4: Exclusion Criteria 
Exclusion 
Criteria 
1. Planned lead modification 
2. Patients with abandoned leads (includes: RV/RA/LV) 
3. Patients undergoing second or subsequent pulse generator change 
4. Patient has permanent atrial arrhythmias  
5. Limited life expectancy or medical condition that would not allow 
completion of the study 
6. Patient is known to be pregnant or breastfeeding at the time of consent 
7. Limited range of mobility of the implant location arm 
8. Patient is unable to climb on and off an examination table unassisted 
9. Patients deemed hemodynamically unstable  
10. 
Subject Accountability 
10.1. 
Point of Enrollment 
Subjects will be considered enrolled once they meet all the inclusion criteria (Table 
3), and none of the exclusion criteria (Table 4), and they have signed the informed 
consent form. Note: All subjects must be consented after they have had their 
device system implanted for three months.  
10.2. 
Withdrawal 
All subjects enrolled in the clinical study (including those withdrawn from the 
clinical study) shall be accounted for and documented. If a subject withdraws from 
the clinical investigation, the reason(s) shall be reported in the eCRF.   
 
11. 
Study Methods 
11.1. 
Data Collection 
The data collection schedule is shown in Table 5. 
 
 

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Table 5: Study Data Collection 
Procedure/Assessment 
Screening 
and 
Enrollment 
Imaging
* 
 
Informed Consent Process (Includes 
signature/date and documentation) 
X 
 
Physical Assessment (Including recent Weight 
and Height) 
X^ 
 
Pregnancy test*** 
X 
 
Implant procedure information (Including date 
of implant, venous access technique) 
X^ 
 
All currently implanted lead details (Including 
Lead Type, model/serial number, manufacturer, 
positioning of the lead, and age of existing lead) 
X^ 
 
Currently implanted pulse generator details 
(Including Pulse Generator type, model/serial, 
manufacturer, position of pulse generator) 
X^ 
 
Medical History (Including birthdate, race, 
ethnicity, gender, most recent ejection fraction) 
X^ 
 
Most recent Chest X-ray** 
X^ 
 
Schedule Imaging Procedure*  
X 
 
Intra-Cardiac Imaging 
 
X 
Calibration Object Imaging 
 
X 
Shoulder Movement-1 Imaging 
 
X 
Calibration Object Imaging 
 
X 
Shoulder Movement-2 Imaging 
 
X 
Calibration Object Imaging 
 
X 
Adverse Events Assessment 
 
X 
* 
Imaging procedure must occur at least 3 months post implant  
** 
Provide most recent AP/PA Chest X-ray post implant of current system, if available 
*** Women of childbearing potential must have a pregnancy test within 7 days prior to required 
imaging to confirm study eligibility 

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^ 
Specific data items should be collected, if available 
 
Imaging Protocol 
Prior to the protocol required imaging, the biplane fluoroscopy imaging cameras 
will be positioned at the head end of the table. Collection of images should be 
conducted by a site staff member qualified to obtain fluoroscopy and trained on 
the protocol.   
For each image sequence, the subject will lay on the table in a supine position and 
exit the table once the image sequence is complete.  After the subject image is 
taken, a calibration object (AAMI_PC_WG1_N741, HUCS Calibration Object) will 
be placed on the table and imaged in the same fashion.   
Note: Incidental findings (i.e. lead dislodgement noted prior to start of arm 
movement or an unknown mass of tissue in the area of the imaging) will be 
reported to the subject’s primary care provider or following physician per medical 
discretion.  Incidental findings will not be discussed or collected as a part of the 
study. 
Image Sequence 1: 
Intra-cardiac Imaging Protocol 
1. 
Subjects will be asked to assume a supine position with their arms by their 
sides (Figure 11A) in the biplane system field of view and coached to 
perform a breath-hold maneuver for a period of 5 seconds and be given 
specific instructions on when to do so. 
2. 
Subjects will have ECG electrodes placed, and the signal continually 
recorded. 
3. 
Short taps of the fluoroscopy pedal (scout films) will be used to optimize 
both Image Intensifier (II) positions to ensure adequate visualization of the 
RV lead through its intra-cardiac course. Image Intensifiers shall be at an 
angle of 90°±45° to each other. Lowest intensity exposure at 7.5 frames/ 
second or less will be used for this purpose. (Approximately 4 seconds) 
Note: It is required that for each image sequence the entire intracardiac 
region must be visible throughout the entire image sequence. 
4. 
A breath-hold biplane cine-fluoroscopy capture (15 frames/ second or 
more) of two cardiac cycles (3 seconds) will be acquired. 
5. 
At this time disconnect the ECG cables and have the subject leave the 
imaging field without moving the x-ray cameras (image intensifiers).  
6. 
A calibration object will be placed in the field of view, and adjusted without 
moving the x-ray camera, until a minimum of 12 markers are visible in both 
views. 
7. 
The calibration object will be imaged without moving the biplane system 
(approximately 1 second) 

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Image Sequence 2: 
Shoulder movement-1 (Arm along body movement) Imaging Protocol 
Note: If the PG is implanted on the left, the left arm will be in motion; if 
implanted on the right, the right arm will be in motion. 
1. 
Subjects will be asked to assume a supine position in the biplane system 
field of view, and coached to perform a movement at a starting point with 
the arm on the table alongside the body (Figure 11A) to follow a course 
along the long axis of the body as high as possible (Figure 11B). 
2. 
Short taps of fluoroscopy will be used to optimize adequate visualization of 
the suture-sleeve and connector regions of the defibrillator/pacing lead in 
the center of the imaging plane of both Image Intensifiers during this arm 
movement. Image Intensifiers shall be at an angle of 90°±45° to each 
other. Lowest intensity exposure at 7.5 frames/ second or less will be used 
for this purpose. (Approximately 4 seconds each) Note: It is required that 
for each image sequence the PG and entire extracardiac region (including 
the venous access site) must be visible throughout the entire image 
sequence. 
3. 
A cine- fluoroscopy exposure capture (15 frames/second or more) of the 
defibrillator/pacing lead will be acquired during the arm along body 
movement. (3 seconds) 
4. 
Have the subject leave the imaging field without moving the x-ray cameras. 
5. 
A calibration object will be placed in the field of view, and adjusted without 
moving the x-ray camera, until a minimum of 12 markers are visible in both 
views. 
6. 
The calibration object will be imaged without moving the biplane system 
(approximately 1 second) 
Image Sequence 3: 
Shoulder movement-2 (Cross-chest movement) Imaging Protocol 
1. 
Note: If the PG is implanted on the left, the left arm will be in motion; if 
implanted on the right, the right arm will be in motion. Subjects will be 
asked to assume a supine position in the biplane system field of view, and 
coached to perform a movement at a starting point with the arm on the 
table alongside the body (Figure 11A) to follow a course across the chest 
(Figure 11C). 

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2. 
Short taps of fluoroscopy will be used to optimize adequate visualization of 
the suture-sleeve and connector regions of the defibrillator/pacing lead in 
the center of the imaging plane of both Image Intensifiers during this arm 
movement. Image Intensifiers shall be at an angle of 90°±45° to each 
other. Lowest intensity exposure at 7.5 frames/ second or less will be used 
for this purpose. (approximately 4 seconds each) Note: It is required that 
for each image sequence the PG and entire extracardiac region (including 
the venous access site) must be visible throughout the entire image 
sequence. 
3. 
A cine- fluoroscopy exposure capture (15 frames/second or more) of the 
RV lead will be acquired during the arm along body movement. (3 seconds) 
4. 
Have the subject leave the imaging field without moving the x-ray cameras 
for the final time. 
5. 
A calibration object will be placed in the field of view, and adjusted without 
moving the x-ray camera, until a minimum of 12 markers are visible in both 
views. 
6. 
The calibration object will be imaged without moving the biplane system 
(approximately 1 second) 
 
Figure 11: Illustrations of prescribed arm positions 
A: Arms down, B: Arm overhead, and C: Arm across chest 
 
11.2. 
 Imaging Data recorded 
1. 
For the intra-cardiac region, DICOM data files (with ECG signal, if available) 
shall be reported for each frame.   
2. 
For the extra-venous region, DICOM data files shall be reported for each 
frame. 
3. 
For the connector region, DICOM data files shall be reported for each frame. 
Note: all images for one subject should be placed on the same DICOM media. 
A: 
B: 
C: 

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11.3. 
Informed Consent 
Prior to initiation of any study specific procedures including data collection, an 
institutional review board (IRB) approved Informed Consent Form must be signed 
and dated by the subject. Documentation of the informed consent process is 
required for each subject and should be maintained within the electronic medical 
record, per hospital policy. 
If informed consent is obtained the same day the subject begins participating in 
study-related procedures, it should be documented that informed consent was 
obtained prior to participation in any study-related procedures. The signed 
Informed Consent Form must be kept in the hospital/clinic medical chart or with 
the study subject documentation and be available for monitoring and auditing, if 
applicable. A copy of the Informed Consent Form must be given to the subject. 
11.4. 
Source Documents 
It is preferable that original source documents are maintained at the center, when 
available. Where copies of the original source document as well as printouts of 
original electronic source are retained, these shall be signed and dated by a 
member of the study team.  All source documentation that is provided to DCRI 
must have the personal health identifiers redacted and be labeled with the subject 
study identifier. Source documentation includes but is not limited to those items 
noted in Table 6. 
Table 6: Source Documentation Requirements 
Requirement 
Disposition 
Medical 
history, 
physical 
assessment 
and 
Implant/Lead related data 
Retain at site 
Biplane Fluoroscopy DICOM 
Retain original at site, and 
provide a copy to DCRI 
Synced ECG data (if available)  
Retain original at site, and 
provide a copy to DCRI 
Historical and Implant related X-ray images (AP/PA 
view), if available 
Retain original at site, and 
provide a copy to DCRI 
12. 
Data Management 
12.1. 
Data Collection, Processing, and Review 
Subject data will be recorded in a limited access secure electronic data capture 
(EDC) system.  

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The EDC database will reside on a production server hosted by a system specified 
by DCRI. All changes made to the clinical data will be captured in an electronic 
audit trail and available for review by the sponsor or its representative. The 
associated software and database have been designed to meet regulatory 
compliance for deployment as part of a validated system compliant with laws and 
regulations applicable to the conduct of clinical studies pertaining to the use of 
electronic records and signatures. Database backups are performed regularly. 
The Investigator provides his/her electronic signature on the appropriate 
electronic case report forms (eCRFs) in compliance with local regulations. A 
written signature on printouts of the eCRFs must also be provided if required by 
local regulation. Any data changes to forms previously signed by the investigator 
will require new signatures by the investigator, acknowledging and approving the 
changes. 
Visual and/or electronic data review will be performed to identify possible data 
discrepancies. Manual and/or automatic queries will be created in the EDC system 
and will be issued to the site for appropriate response. Site staff will be responsible 
for resolving all queries in the database. 
12.2. 
Data Retention 
The Principal Investigator or his/her designee or Investigational site will maintain 
all essential study documents and source documentation that support the data 
collected on the study subjects in compliance with applicable regulatory 
requirements.   
The Principal Investigator or his/her designee will take measures to prevent 
accidental or premature destruction of these documents. If for any reason the 
Principal Investigator or his/her designee withdraws responsibility for maintaining 
these essential documents, custody must be transferred to an individual who will 
assume responsibility and DCRI must receive written notification of this custodial 
change. Sites are required to inform DCRI in writing where paper or electronic 
files are maintained in case files are stored off site and are not readily available. 
12.3. 
External Laboratories 
The National Institute of Standards and Technology, NIST will perform the final 
data analysis for the lead imaging collected during the HUCS study.  NIST will 
prepare the lead analyses, which will be reviewed by the members of the AAMI 
CRMD Committee Leads Working Group and approved by the lead manufacturers. 
This report will be codified into a new AAMI Standard for pacing and defibrillator 
leads.   

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13. 
Deviations 
An Investigator must not make any changes or deviate from this protocol, except 
to protect the life and physical well-being of a subject in an emergency. An 
investigator shall notify DCRI and the reviewing IRB of any deviation from the 
investigational plan to protect the life or physical well-being of a subject in an 
emergency, and those deviations which affect the scientific integrity of the clinical 
investigation. Such notice shall be given as soon as possible, but no later than 5 
working days after the emergency occurred, or per prevailing local requirements, 
if sooner than 5 working days.  
All deviations from the investigational plan, with the reason for the deviation and 
the date of occurrence, must be documented and reported to the sponsor using 
the study EDC system. Sites may also be required to report deviations to the IRB, 
per local guidelines and government regulations.  
14. 
Compliance 
14.1. 
Statement of Compliance 
This study has been determined by the sponsor to be a nonsignificant risk device 
study subject to the abbreviated requirements specified by 21 CFR Part 812.2(b), 
in addition conformance to Part 50, 54, and 56 will be required. The study may 
not begin until the required IRB approval is obtained.  Additionally, the site may 
not begin participation until formal authorization to enroll is provided by DCRI. 
14.2. 
Investigator Responsibilities 
The Principal Investigator of an investigational site is responsible for ensuring that 
the study is conducted in accordance with the Clinical Study Agreement, the 
clinical investigation plan, ethical principles that have their origins in the 
Declaration of Helsinki, any conditions of approval imposed by the reviewing IRB, 
and prevailing local and/or country laws and/or regulations, whichever affords the 
greater protection to the subject. 
The Principal Investigator’s responsibilities include, but are not limited to, the 
following.  
• 
Prior to beginning the study, sign the Clinical Study Agreement and comply 
with the Investigator responsibilities as described in such Agreement.   
• 
Prior to beginning the study, sign the Protocol Signature page documenting 
his/her agreement to conduct the study in accordance with the protocol. 
• 
Provide his/her qualifications and experience to assume responsibility for the 
proper conduct of the study through up-to-date curriculum vitae or other 
relevant documentation.  

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• 
Make no changes in or deviate from this protocol, except to protect the life and 
physical well-being of a subject in an emergency; document and explain any 
deviation from the approved protocol that occurred during the course of the 
clinical investigation. 
• 
Create and maintain source documents throughout the clinical study and 
ensure their availability with direct access during potential monitoring visits or 
audits; ensure that all clinical-investigation-related records are retained per 
requirements. 
• 
Ensure the accuracy, completeness, legibility, and timeliness of the data 
reported to DCRI in the eCRFs and in all required reports. 
• 
Record, report, and assess (seriousness and relationship to the procedure) 
every adverse event as applicable per the protocol.  
• 
Report to DCRI, per the protocol requirements, all adverse events (includes 
AE, SAEs).  
• 
Allow DCRI to perform monitoring and auditing activities if applicable and be 
accessible to the clinical research monitor or auditor and respond to questions 
during potential monitoring visits or audit(s). 
• 
Allow and support regulatory authorities and the IRB when performing auditing 
activities. 
• 
Ensure that informed consent is obtained in accordance with applicable laws, 
this protocol and local IRB requirements. 
• 
Provide adequate medical care to a subject during and after a subject’s 
participation in a clinical study in the case of adverse events, as described in 
the Informed Consent Form (ICF). 
• 
Inform the subject of the nature and possible cause of any adverse events 
experienced. 
• 
Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be 
required. 
• 
Ensure that clinical medical records are clearly marked to indicate that the 
subject is enrolled in this clinical study. 
• 
Make all reasonable efforts to ascertain the reason(s) for a subject’s premature 
withdrawal from clinical investigation while fully respecting the subject’s rights. 
• 
Ensure that an adequate investigation site team and facilities exist and are 
maintained and documented during the clinical investigation. 

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Delegation of Responsibility 
When specific tasks are delegated by an investigator, including but not limited to 
conducting the informed consent process, the Principal Investigator is responsible 
for providing appropriate training, are competent to perform the tasks they have 
been delegated and adequate supervision of those to whom tasks are delegated. 
Where there is a sub investigator at a site, the sub investigator should not be 
delegated the primary supervisory responsibility for the site. The investigator is 
accountable for regulatory violations resulting from failure to adequately supervise 
the conduct of the clinical study.  
14.3. 
Institutional Review Board 
The investigational site will obtain the written and dated approval/favorable 
opinion of the IRB for the clinical investigation inclusive of an approved informed 
consent document before recruiting subjects and implementing all subsequent 
amendments, if required. 
A copy of the IRB approval and ICF must be received by DCRI before recruitment 
of subjects into the study.  
Any amendment to the protocol will require review and approval by the IRB before 
the changes are implemented to the study.  All changes to the ICF must be IRB 
approved; a determination will be made regarding whether a new ICF needs to be 
obtained from participants who provided consent, using a previously approved 
ICF.  
Annual IRB approval and renewals will be obtained throughout the duration of the 
study as required by applicable local/country laws or regulations or IRB 
requirements. Copies of the study reports and the IRB continuance of approval 
must be provided to DCRI.  
14.4. 
Sponsor Responsibilities 
All information and data sent to DCRI concerning subjects or their participation in 
this study will be considered confidential by DCRI and will be kept confidential in 
accordance with all applicable laws and regulations. Only authorized DCRI 
personnel and/or a NIST representative, the applicable CIED lead manufacturer’s 
representatives, and AAMI will have access to this information. Authorized 
regulatory personnel have the right to inspect and copy all records pertinent to 
this study. Study data collected during this study may be used by AAMI for the 
purposes of this study, publication, and to support future standards. All data used 
in the analysis and reporting of this study or shared with a third-party researcher 
will be without identifiable reference to specific subjects. 
15. 
Monitoring 
All data is collected at the time of enrollment and imaging; therefore, no on-site 
monitoring is planned. 

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16. 
Potential Risks and Benefits 
16.1. 
Anticipated Adverse Events  
The following potential adverse events (AE) have been identified for the study 
related to the imaging procedure and requirements.  This study will not report 
adverse events associated with the pulse generator or lead implant procedure as 
subjects will already be implanted.  Adverse events associated with the pulse 
generator will not be collected as a part of this trial as the imaging procedure will 
not affect the device.  Table 7 indicates potential adverse events related to 
participation in this study. 
Table 7: Potential Adverse Events 
Potential Adverse Events 
Adverse or allergic reaction to adhesive 
from ECG tabs (i.e. rash, redness etc.) 
Pain or discomfort from required shoulder 
movement 
Dislodgement of the lead (RA/LV/RV) 
Adverse reaction to the imaging 
procedure radiation (See section 16.2.1) 
 
16.2. 
Risks Associated with Participation in the Clinical Study 
This study involves minimal risk to subjects.  Including by not limited to 
fluoroscopy/radiation exposure. It is estimated that it will take approximately 10 
minutes of time to optimally position cameras and acquire images. See specifics 
below. The risk is considered very low and clinically acceptable.  
 
Radiation Exposure  
All study participants will receive standard biplane fluoroscopy x-radiation. X-ray 
exposure has been shown to increase the risk of cancer, as well as excessive 
radiation exposure can cause skin injury, the severity of which depends on dose 
to skin and ranges from hair loss, to skin irritation, to severe skin burns. However, 
the incremental amount of x-ray used in this study is expected to be minimal and 
is not expected to have significant, if any clinical consequence for the subject. 
In a standard x-ray exposure (2D fluoroscopy), the x-ray tube is stationary.  This 
directs the x-radiation to a limited area of skin as it enters the body, reducing the 
potential risk of adverse effects.    

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Radiation exposure can be quantified as “absorbed dose to skin”, in units of Gray 
(Gy).  The National Council on Radiation Protection & Measurement16 provides 
guidance for 2D exposure that can cause injury.  A dose of <2000 mGy is 
considered insignificant or very low.  A dose of 2000 mGy can cause early transient 
erythema (reddening of the skin).17 
A previous lead imaging study performed in the same manner as the study 
imaging procedure in section 11.1.1 showed the absorbed dose to skin, as < 300 
mGy (range 45-287) for an exposure time ≤ 45 seconds (range 22-45).18  This 
exposure time is the same as what is expected for the HUCS study subjects. 
 
To put this dose of radiation into perspective, the following comparisons are 
provided: 
1. 
The absorbed dose to skin for a diagnostic coronary angiography 
procedure has been reported as 1350 mGy (range 900-1910).19 
2. 
The absorbed does to skin for a percutaneous transluminal coronary 
angioplasty (PTCA) is 3760 mGy (range 2400 - 5560). 20 
The radiation exposure is not expected to have any acute adverse effects or any 
discernable effects from the low level of exposure.  However, it is possible that 
following the fluoroscopic procedure, the skin area exposed to the x-rays could 
react to produce an effect similar to a sun burn.   
 
16.3. 
Risk Minimization 
To minimize radiation exposure the principal investigator will train other 
investigators/site staff on optimal techniques to acquire images. Only short taps 
of fluoroscopy will be utilized for scout images. 
To minimize procedural time on the table, laboratory staff will be trained on 
optimal setup procedures.   
These procedures will be done in a clinical or hospital setting. If unforeseen issues 
arise during the procedures (i.e. subject becomes unstable or experiences a 
medical emergency), medical personnel will be available. 
 
16 NCRP Report No. 168, Radiation Dose Management for Fluoroscopically-Guided Interventional Medical 
Procedures, Table 2.5, National Council on Radiation Protection and Measurements, 7910 Woodmont Avenue, 
Suite 400, Bethesda, MD 20814-3095 
17 NCRP Report No. 168, Radiation Dose Management for Fluoroscopically-Guided Interventional Medical 
Procedures, Table 2.5, National Council on Radiation Protection and Measurements, 7910 Woodmont Avenue, 
Suite 400, Bethesda, MD 20814-3095 
18 Internal Medtronic Data (Unpublished) 
19 Mahesh, M. (2001). Fluoroscopy: patient radiation exposure issues. Radiographics, 21(4), 1033-1045 
20 Mahesh, M. (2001). Fluoroscopy: patient radiation exposure issues. Radiographics, 21(4), 1033-1045 

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16.4. 
Anticipated Benefits 
There are no benefits to study subjects participating in the study. The study 
results could benefit future patients who receive defibrillator or pacing leads by 
improving on current test methods and future lead designs.  
No data exists in regard to the use conditions experienced by implanted leads in 
the human population. Defibrillation and Pacing leads are life-saving and life-
sustaining devices that have to withstand the rigors of the human environment to 
function adequately. The gap in this knowledge-base has resulted in multiple 
large-scale recalls with currently existing test methods being unable to predict 
reliable lead performance with new designs with resultant patient deaths, 
morbidity and financial burden on the health care delivery system. It is important 
that a study such as this be performed for the following potential positive 
outcomes: 
Investigate the relationship between lead stiffness and curvature evident 
by imaging in implanted leads which would permit the development of ISO 
standards. The development of these standards will lead to qualifying safer 
products for human implantation. 
Provide manufacturers with quantifiable information across different lead 
designs on the effects of physical stress impacted by shoulder motion, and 
cardiac contraction across variable physical conditions and implanting 
physician techniques.  
Three-D reconstruction of fluoroscopy-derived images on a background of 
cardiac anatomy and implant technique will provide insights into the 
propensity to lead failure over time.  
16.5. 
Risk to Benefit Rationale 
Although there is radiation exposure to the subjects participating in this study, 
the radiation dosage is not enough to cause skin burns or significant increase in 
cancer risk. 
The learnings from this will result in the development of a new standard, which is 
expected to improve the lead reliability of transvenous leads. 
17. 
Adverse Event Reporting 
17.1. 
Reportable Events by investigational site to DCRI 
The investigator will be required to assess and classify each AE that occurs during 
the time of the imaging procedure. AEs that occur following consent, but prior to 
the imaging procedure will not be collected. 

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Events collected during this study will include adverse events, serious adverse 
events and unanticipated adverse events (inclusive of serious) specific to the 
imaging procedure duration.  When possible, the medical diagnosis should be 
reported as the event term, not individual symptoms.  Adverse events must be 
recorded in the eCRF.   Underlying diseases are not reported as an adverse event.   
17.2. 
Definitions 
 
Adverse Event Definitions 
An adverse event (AE) is defined as any untoward medical occurrence, unintended 
disease or injury, or untoward clinical signs (including abnormal laboratory 
findings) in subjects that occurs during the course of the study (defined as 
occurring during the imaging procedure), whether or not directly related to the 
imaging procedure. 
Adverse Events are classified as a serious adverse event (SAE) as defined by 
MEDDEV 2.7/3 if one or more of the following consequences are fulfilled: 
• 
led to death 
• 
led to serious deterioration in the health of the subject as defined by either: 
o a life-threatening illness or injury or 
o a permanent impairment of a body structure or function or 
o in-patient hospitalization (>24 hours) or prolongation of existing 
hospitalization or 
o a medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or function 
• 
led to fetal distress, fetal death, or a congenital abnormality or birth defect 
17.3. Relationship to Study Procedure 
The Investigator must assess the relationship of the reportable AE to the study 
procedure. See criteria in Table 8. 

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Table 8: Criteria for Assessing Relationship of Study Procedure to 
Adverse Event 
Classification 
Description 
Not Related 
Def 
based 
off 
intent of MEDDEV 
2.7/3 
Relationship to the procedures can be excluded when: 
- the event is not a known side effect of the procedures; 
- the event has no temporal relationship with the procedures; 
- the serious event does not follow a known response pattern to 
the medical device (if the response pattern is previously known) 
and is biologically implausible; 
- the discontinuation of or the reduction of the level of 
activation/exposure - when clinically feasible – and reintroduction 
of it (or increase of the level of activation/exposure), do not impact 
the serious event; 
- the event involves a body-site or an organ not expected to be 
affected by the procedure; 
- the serious event can be attributed to another cause (e.g. an 
underlying or concurrent illness/ clinical condition, an effect of 
another device, drug, treatment or other risk factors); 
In order to establish the non-relatedness, not all the criteria listed 
above might be met at the same time, depending on the type of 
procedures and the serious event. 
Unlikely Related 
Def 
based 
off 
intent of MEDDEV 
2.7/3 
The relationship with the procedure seems not relevant and/or the 
event can be reasonably explained by another cause, but additional 
information may be obtained. 
Possibly Related 
Def 
based 
off 
intent of MEDDEV 
2.7/3 
The relationship with the procedure is weak but cannot be ruled out 
completely. Alternative causes are also possible (e.g. an underlying 
or concurrent illness/ clinical condition or/and an effect of another 
device, drug or treatment). Cases were relatedness cannot be 
assessed or no information has been obtained should also be 
classified as possible. 
Probably 
Related 
Def 
based 
off 
intent of MEDDEV 
2.7/3 
The relationship with the procedure seems relevant and/or the 
event cannot be reasonably explained by another cause, but 
additional information may be obtained. 

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Classification 
Description 
Causal 
Relationship 
Def 
based 
off 
intent of MEDDEV 
2.7/3 
The serious event is associated with the procedures beyond 
reasonable doubt when: 
- the event is a known side effect of the procedures; 
- the event has a temporal relationship with procedures; 
- the event involves a body-site or organ that the procedures are 
applied to; 
-the procedures have an effect on; 
- the discontinuation of the procedure (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of 
the level of activation/exposure), impact on the serious event 
(when clinically feasible); 
- other possible causes (e.g. an underlying or concurrent illness/ 
clinical condition or/and an effect of another device, drug or 
treatment) have been adequately ruled out; 
- harm to the subject is due to error in use; 
In order to establish the relatedness, not all the criteria listed above 
might be met at the same time, depending on the type of 
device/procedures and the serious event. 
 
17.4. 
Adverse Event Reporting to DCRI 
The investigator shall report to DCRI, by completing the Adverse Event eCRF:  
• 
AEs that are classified by the investigator as related to the imaging procedure  
• 
AEs that occur following imaging that are classified by the investigator as 
related to the imaging procedure 

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17.5. 
Investigator Reporting Requirements 
The requirements for investigators to report relevant adverse events (see section 
16.1) to DCRI are as shown in Table 9. 
Table 9: Communication requirements for reporting to DCRI 
Event Classification 
Communication Method  Communication Timeline  
Serious Adverse Event  
Complete AE eCRF page 
with all available new and 
updated information.  
Within 3 calendar days of first 
becoming aware of the event or as per 
local/regional regulations.  
Reporting required through the end of 
the study participation 
Provide all relevant source 
documentation 
(de-
identified/ 
pseudonymized) 
for 
reported event. 
At request of DCRI 
Adverse Event  
Complete AE eCRF page, 
which 
contains 
such 
information as date of AE, 
treatment 
of 
AE 
resolution, assessment of 
seriousness 
and 
relationship to the device.  
Provide all relevant source 
documentation 
(de-
identified/pseudonymized
) for reported event.  
In a timely manner (e.g. Recommend 
within 10 business days) after 
becoming aware of the information 
Reporting required through the end of 
the study subject participation.   
 
 
The requirements for investigators to report other information to DCRI are as 
shown in Table 10. 
Table 10: Additional Investigator Reporting Responsibilities 
Type of 
Report 
Report to 
DCRI 
Report to 
IRB 
Time Constraints of Notification 
Subject 
Withdrawal 
Required 
As 
Required 
Within 5 working days after notification of the 
event 
Withdrawal of 
IRB Approval 
Required 
N/A 
Within 5 working days of receipt of notice of 
withdrawal of approval 
Progress 
Report 
Required 
Required 
At, minimum annually 

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Significant 
Deviations 
from 
Investigational 
Plan 
Required 
Required 
Within 5 working days after emergency to 
protect life or physical well-being of subject, 
otherwise prior approval by DCRI is required 
Informed 
Consent Not 
Obtained 
Required 
Required 
Within 5 working days of occurrence 
17.6. 
Reporting Responsibilities to IRB  
DCRI is responsible for reporting summary adverse event information to all 
participating investigators and IRBs, as applicable (refer to Table 11). 
The Principal Investigator is responsible for informing the IRB of SAE and other 
applicable information as required by local/regional regulations. 
 
17.7. 
DCRI Records and Reports 
DCRI will maintain the following records: 
• 
All correspondence with the investigator(s) and IRBs that pertains to the 
study 
• 
Protocol signature page, delegation/signature logs and curriculum vitae 
• 
Name and address of each investigator and each IRB that is involved with 
the investigation 
• 
Adverse events  
• 
Electronic Case Report Form data 
• 
Confirmation of completed subject informed consent forms 
• 
Clinical investigation protocol and report of prior investigations 
• 
Clinical progress reports 
• 
Any other information upon the request of an IRB or regulatory authority 
• 
Table 11 outlines the responsibilities, including time constraints, for sponsor 
reports. 

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Table 11: DCRI Sponsor Reporting Responsibilities 
Type of Report 
Prepared by 
DCRI for 
Time Constraints 
of Notification 
Withdrawal of IRB 
approval 
All 
reviewing 
IRBs, 
participating 
investigators, 
AAMI 
Project Lead 
Within 5 working days of receipt of 
notice of withdrawal of approval 
Progress report 
All 
reviewing 
IRBs, 
AAMI Project Lead 
Submitted at least annually 
Final report 
All 
reviewing 
IRBs, 
participating 
investigators, 
AAMI 
Project Lead 
A final report will be submitted within 
6 
months 
after 
completion 
or 
termination of the study 
Informed consent not 
obtained 
Overseeing IRB 
Within 5 working days of notification 
of occurrence 
18. 
Additional Study Conditions 
18.1. 
Informed Consent 
Subject participation in this clinical study is voluntary.  Informed Consent is 
required from each subject. The Investigator is responsible for ensuring that 
Informed Consent is obtained prior to the study-required imaging procedures 
and/or data collection.  
The obtaining and documentation of Informed Consent must be in accordance 
with the principles of the Declaration of Helsinki, and the reviewing IRB The ICF 
must be accepted by the and approved by the site’s IRB or central IRB, if 
applicable. 
DCRI will provide a study-specific template of the ICF to investigators participating 
in this study. The ICF template may be modified to meet the requirements of the 
investigative site’s IRB.  Any modification requires acceptance from DCRI prior to 
use of the form. Privacy language shall be included in the body of the form or as 
a separate form as applicable.   
The process of obtaining Informed Consent shall at a minimum include the 
following steps, as well as any other steps required by applicable laws, rules, 
regulations and guidelines: 
• 
be conducted by the Principal Investigator or designee authorized to 
conduct the process 
• 
include a description of all aspects of the clinical study that are relevant to 
the subject’s decision to participate throughout the clinical study 
• 
avoid any coercion of or undue influence of subjects to participate 

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• 
not waive or appear to waive subject’s legal rights 
• 
use native language that is non-technical and understandable to the subject  
• 
provide ample time for the subject to consider participation and ask 
questions if necessary 
• 
ensure important new information is provided to new and existing subjects 
throughout the clinical study 
The ICF shall always be signed and personally dated by the subject competent to 
sign the ICF under the applicable laws, rules, regulations and guidelines and by 
the investigator and/or an authorized designee responsible for conducting the 
informed consent process. The original signed ICF will be retained by the site and 
a copy of the signed and dated document and any other written information must 
be given to the person signing the form.  
Failure to obtain subject consent will be reported by DCRI to the applicable 
regulatory authority according to their requirements (e.g., specific IRB reporting 
time frame). Any violations of the informed consent process must be reported as 
deviations to the sponsor and local regulatory authorities (e.g. IRB), as 
appropriate. 
If new information becomes available that can significantly affect a subject's 
future health and medical care, that information shall be provided to the affected 
subject(s) in written form via a revised ICF or, in some situations, enrolled 
subjects may be requested to sign and date an addendum to the ICF. In addition 
to new significant information during the course of a study, other situations may 
necessitate revision of the ICF, such as if there are amendments to the applicable 
laws, protocol, a change in Principal Investigator, administrative changes, or 
following annual review by the IRB. The new version of the ICF must be approved 
by the IRB. Acceptance by DCRI is required if changes to the revised ICF are 
requested by the site’s IRB. The IRB will determine the subject population to be 
re-consented. 
18.2. 
Termination of Study Participation by the Investigator or 
Withdrawal of IRB Approval 
Any investigator, or associated IRB or regulatory authority may discontinue 
participation in the study or withdraw approval of the study, respectively, with 
suitable written notice to DCRI. Investigators, associated IRBs, and regulatory 
authorities, as applicable, will be notified in writing in the event of these 
occurrences. 
18.3. 
Requirements for Documentation and Subject Follow-up 
In the event of premature study termination, a written statement as to why the 
premature termination has occurred will be provided to DCRI. The IRB and 
regulatory authorities, as applicable, will be notified. Detailed information on how 
enrolled subjects will be managed thereafter will be provided.  

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In the event an IRB terminates participation in the study, participating 
investigators, associated IRBs, and regulatory authorities, as applicable, will be 
notified in writing. Detailed information on how enrolled subjects will be managed 
thereafter will be provided by DCRI. 
In the event a Principal Investigator terminates participation in the study, study 
responsibility will be transferred to another investigator, if possible. In the event 
there are no opportunities to transfer Principal Investigator responsibility; detailed 
information on how enrolled subjects will be managed thereafter will be provided 
by DCRI. 
The Principal Investigator or his/her designee must return all study-related 
documents to DCRI, unless this action would jeopardize the rights, safety, or 
welfare of the subjects. 
18.4. 
Criteria for Suspending/Terminating a Study Site 
DCRI reserves the right to stop the inclusion of subjects at a study site at any 
time after the study initiation visit if no subjects have been enrolled for a period 
beyond 3 months after site initiation, or if the site has multiple or severe protocol 
violations/noncompliance without justification and/or fails to follow remedial 
actions. 
The IRB and regulatory authorities, as applicable, will be notified. Study subjects 
will be contacted, as applicable, and be informed of changes to study visit 
schedule. 
19. 
Publication Policy 
AAMI CRMD Committee Leads Working Group requires disclosure of its 
involvement as a financial supporter in any publication or presentation relating to 
an AAMI CRMD Committee Leads Working Group study or its results. AAMI CRMD 
Committee Leads Working Group will submit study results for publication 
(regardless of study outcome) following the conclusion or termination of the 
study. AAMI CRMD Committee Leads Working Group adheres to the 
Contributorship Criteria set forth in the Uniform Requirements of the International 
Committee of Medical Journal Editors (ICMJE; http://www.icmje.org).  
In order to ensure the public disclosure of study results in a timely manner, while 
maintaining an unbiased presentation of study outcomes, AAMI CRMD Committee 
Leads Working Group personnel may assist authors and investigators in 
publication preparation provided the following guidelines are followed:  
• 
All authorship and contributorship requirements as described above must 
be followed. 
• 
AAMI CRMD Committee Leads Working Group involvement in the 
publication preparation and the AAMI CRMD Committee Leads Working 
Group Publication Policy should be discussed with the Principal 
Investigator(s) at the onset of the project. 

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• 
The CIED lead manufacturers are the primary drivers of decisions regarding 
publication content, review, approval, and submission.  
The data, analytic methods, and study materials for this clinical trial may be made 
available to other researchers on approval from all the lead manufacturers.  
 
20. 
Abbreviations and Definitions  
20.1. 
Abbreviations 
AE: 
Adverse Event 
AAMI:  
Association for Advancement of Medical Instrumentation 
AAMI CRMD:  
Association for the Advancement of Medical Instrumentation 
Cardiac Rhythm Management Device Committee 
AAMI WG01:  
Association for the Advancement of Medical Instrumentation 
Technical Working Group 1 
ABT:  
Abbott 
BIO:  
Biotronik 
BSC:  
Boston Scientific Corporation 
CIED:  
Cardiac implantable electrical device 
Co-I:  
Co Investigator 
CRC:  
Clinical Research Coordinator 
CSA:  
Clinical Study Agreement 
DCRI: 
Duke Clinical Research Institute 
DICOM:  
Digital Imaging and Communications in Medicine 
eCRF: 
Electronic Case Report Form 
ECG: 
Electrocardiogram 
FDA:  
Food and Drug Administration 
Fps: 
Frames per second 
HUCS:  
Human Use Condition Study 
ICD:  
Implantable Cardioverter Defibrillator 
ICF:   
Informed Consent Form 
II:  
Image Intensifier 
IRB:  
Institutional Review Board 
ISO:  
International Standards Organization 
MDT:  
Medtronic 

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mGy:  
milligray 
NIST:  
National Institute of Standards and Technology 
PI:  
Principal Investigator 
RV:  
Right Ventricular 
SAE: 
Serious Adverse Event 
SADE: 
Serious Adverse Device Effect 
SDO:  
Standards Developing Organization 
2D: 
Two-Dimensional 
3D:  
Three-Dimensional