ECG Belt to Assess Electrical Synchronization in Patients With Left Bundle Branch Pacing and His-Purkinje Conduction System Optimized Cardiac Resynchronization Therapy (ECG Belt)
Phase: NA
Conditions: Bradycardia, Heart Failure
Sponsor: Pugazhendhi Vijayaraman

 
 
 
CONFIDENTIAL AND PROPRIETARY 
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Research Protocol – 2020_0465 
ECG Belt to Assess Electrical Synchronization in Patients with Left bundle branch Area 
Pacing and His-Purkinje Conduction System Optimized Cardiac Resynchronization 
Therapy (ECG Belt) 
Version: 1.0 
 
 
27 August 2019 
 
 
 
 
        2.0 
 
       7 October 2020 
 
 
 
Principal Investigator: 
Pugazhendhi Vijayaraman, MD 
Regional Director, Cardiac Electrophysiology, Geisinger Northeast 
Program Director, Geisinger Clinical Cardiac Electrophysiology 
Fellowship Program 
 
 
 
 
 
Geisinger Clinic 
 
 
 
 
1000 E. Mountain Blvd 
 
 
 
 
Wilkes-Barre, PA 18711 
 
 
 
 
570-808-6020 
 
 
 
 
pvijayaraman1@geisinger.edu 
 
 
 
 
 
 
 
Funding Source: Funding for the conduct of this investigator-initiated trial was provided by   
Medtronic’s External Research Program (ERP). 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prepared with assistance from Geisinger Clinical Research 

 
 
 
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PROTOCOL SIGNATURE PAGE 
All necessary sponsor personnel and/or designees have reviewed and approved the ECG Belt to 
Assess Electrical Synchronization in Patients with Left bundle branch Area Pacing and His-
Purkinje Conduction System Optimized Cardiac Resynchronization Therapy (ECG Belt) 
protocol.  
 
The sponsor hereby gives approval to Dr. Pugazhendhi Vijayaraman and Geisinger Clinic to 
proceed with this study as outlined in the above-mentioned protocol.  
 
Authorized Sponsor Signature 
The signature below indicates that you have the authority from the sponsor to approve this 
protocol. 
 
 
 
       Signature of Authorized Signer 
 
 
            Date 
 
 
 
 
 
 
                  Title of Signer 
 
 
Primary Investigator Signature 
The signature below indicates that you, as Primary Investigator, approve this protocol. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
       Signature of Primary Investigator  
 
               Date 
 
 
   Pugazhendhi Vijayaraman, MD 
 
 
Regional Director, Cardiac Electrophysiology, Geisinger Northeast 
 
                      Title of Primary Investigator 
 
      Printed Name of Signer 
      Printed Name of Primary Investigator 

 
 
 
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TABLE OF CONTENTS  
1 
ABBREVIATIONS USED IN THE PROTOCOL ................................................................5 
2 
BACKGROUND AND SIGNIFICANCE .............................................................................5 
3 
OBJECTIVES ........................................................................................................................6 
3.1 
General Objective .........................................................................................................6 
3.2 
Specific Objective .........................................................................................................6 
4 
STUDY DESIGN ...................................................................................................................6 
4.1 
Description ....................................................................................................................6 
4.2 
Study Population ...........................................................................................................7 
4.2.1 
Approximate Number of Subjects ..................................................................7 
4.2.2 
Inclusion Criteria ............................................................................................7 
4.2.3 
Exclusion Criteria ...........................................................................................8 
4.3 
Recruitment ...................................................................................................................8 
4.4 
Study Duration ..............................................................................................................8 
4.4.1 
Approximate Duration of Subject Participation .............................................8 
4.4.2 
Approximate Duration of Study .....................................................................8 
4.5 
Procedures .....................................................................................................................9 
4.5.1 
Schedule of Events .......................................................................................11 
4.6 
Primary Endpoints ......................................................................................................12 
4.7 
Secondary Endpoints ..................................................................................................12 
4.8 
Statistics ......................................................................................................................12 
4.9 
Data Management .......................................................................................................13 
4.9.1 
Data Collection and Storage .........................................................................13 
4.9.2 
Records Retention ........................................................................................14 
5 
SAFETY MONITORING ....................................................................................................14 
5.1 
Adverse Event Reporting ............................................................................................14 
5.2 
Other Reportable Information. ....................................................................................15 
6 
PROTECTION OF HUMAN SUBJECTS ...........................................................................15 

 
 
 
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6.1 
Informed Consent and HIPAA Authorization ............................................................15 
6.2 
Protection of Human Subjects Against Risks .............................................................16 
7 
PUBLICATION PLAN ........................................................................................................16 
8 
REFERENCES .....................................................................................................................17 
 

 
 
 
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1 
 ABBREVIATIONS USED IN THE PROTOCOL 
 
Abbreviation 
Term 
ACE 
Angiostatin-converting enzymes 
AE 
Adverse Event 
ARB 
Angiotensin Resistant II Blockers 
CFR 
Code of Federal Regulation 
CRT 
Cardiac Resynchronization Therapy 
EHR 
Electronic Health Record 
GCP 
Good Clinical Practice 
GIRB 
Geisinger Institutional Review Board 
HBP 
His-Bundle Pacing 
HIPAA 
Health Insurance Portability and Accountability Act 
HOT-CRT 
His-Optimized Cardiac Resynchronization Therapy 
IRB 
Institutional Review Board 
LBB 
Left Bundle Branch  
LBBP 
Left Bundle Branch Area Pacing 
LV 
Left Ventricular Pacing 
NYHA 
New York Heart Association 
PHI 
Personal Health Information 
RVP 
Right Ventricular Pacing 
SAE 
Serious Adverse Event 
WHO 
World Health Organization 
 
 
2 
BACKGROUND AND SIGNIFICANCE 
Physiologic pacing has become rapidly accepted into clinical practice. His bundle pacing (HBP) 
has recently been incorporated into Guideline document for bradycardia pacing.1 Advances have 
been made in physiologic pacing in the form of left bundle branch area pacing (LBBAP). Recent 
report by Huang et al2 described a novel approach to implanting the Medtronic 3830 lead in the 
Left bundle branch area via right ventricular, deep septal approach. Early experience suggests 
that LBB pacing can result in significant improvement in LV function in patients with LBBB and 
heart failure. The potential advantage of this method is several fold:3 1.  Bypass the site of 
conduction block in patients with LBBB (even in patients where His bundle pacing fails to 
correct the LBBB) 2. Achieve low capture threshold with excellent sensing 3. Obtain LV 

 
 
 
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endocardial pacing in addition to conduction system pacing without a lead in the LV endocardial 
cavity. 
 
The electrophysiological and ECG characteristics of LBB Pacing has not been well described. 
The ECG Belt can help assess the difference between baseline, RV pacing, LBBAP and His (or 
LBBAP) Optimized CRT (HOT-CRT) and understand the electrical synchrony and 
characteristics of physiologic pacing. 
 
3 
OBJECTIVES 
3.1 
General Objective 
The objective of the study is to assess the utility of ECG Belt to understand the conduction and 
ECG characteristics of LBBAP and HOT-CRT and compare with preexisting data in traditional 
CRT and RVP.  
3.2 
Specific Objective 
• To demonstrate and establish electrical resynchronization using ECG Belt Research 
System in LBBP and HOT-CRT.  
• To assess ECG Belt derived native conduction parameters and compare them to LBBAP 
and HOT-CRT. 
• To compare with historic ECG belt parameters obtained for right ventricular pacing/ 
Biventricular pacing in prior studies (Bank et al)4 
 
4 
STUDY DESIGN 
4.1 
Description 
The ECG Belt study is a prospective, single-center, investigational, pre-market research study.  
The study team will identify all patients who satisfy the inclusion and exclusion criteria.  The 
study team will evaluate the ECG Belt Research System to assess the electrical characteristics of 
conduction system pacing in patients with preexisting LBBAP or HOT-CRT. 
 

 
 
 
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Eligible patients would have successfully undergone LBBAP using Medtronic 3830 lead and 
C315His sheath. LBBAP will be confirmed at implant using left bundle potentials recorded from 
the lead, ECG morphology during unipolar and bipolar pacing, peak LV activation time and lead 
depth in the LV septum by contrast at implant and 2D echo post-implant. 
 
ECG belt would be used to record ECG during baseline rhythm, LBBAP in unipolar and bipolar 
configurations and / or during HOT-CRT using HBP or LBBAP. These ECG belt characteristics 
would then be compared with baseline and existing data on RV pacing and traditional 
Biventricular pacing. 
 
4.2 
Study Population 
4.2.1 Approximate Number of Subjects 
Approximately 20 patients will participate in the ECG Belt study to be conducted at Geisinger 
Heart Institute. 
 
All patients will share the same recruitment process, inclusion and exclusion criteria and same 
procedures.  
 
4.2.2 Inclusion Criteria 
The following is the inclusion criteria for the ECG Belt study: 
1. Patients > 18 years of age 
2. Patient has a previously implanted LBBAP lead for bradycardia indication or heart failure 
indication with one of the following at Geisinger within the last 5 years: 
• LBBAP 
• LBBAP+LV lead 
• HBP+LV 
3. Patient is willing to comply with all study procedures and be available for the duration of 
the study. 

 
 
 
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4.2.3 Exclusion Criteria 
The following patients or situations are excluded in the ECG Belt study: 
1. Inability to provide informed consent 
2. Pregnant 
3. Enrolled in a concurrent study that may confound the results of this study.  
4.3 
Recruitment 
Potential participants will be identified by clinician referrals, or by review of the electronic 
health record (EHR) of patients.  Research staff will contact potential subjects and invite them to 
participate.    
 
4.4 
Study Duration 
4.4.1 Approximate Duration of Subject Participation 
Subjects will participate in the study for approximately 1 week (+/- 5 days). This includes a 
monitoring (follow up) period which starts immediately after signing the Informed Consent and 
completing the baseline visit (visit 1).    
4.4.2 Approximate Duration of Study 
This study will be completed in approximately 12-15 months duration.  The end of the ECG Belt 
study is the completion of data entry and statistical analysis.  
This study duration approximation is composed of the following stages: 
• Screening and Enrollment Stage – enrollment of 20 patients from Geisinger Heart 
Institute is expected to take 10-12 months based on enrollment rate of 1 to 2 subjects per 
month.  
• Monitoring Stage – based on the planned 1 week monitoring period for each patient, last 
patient completed is expected 10-12 months from the study beginning.  

 
 
 
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• Data Collection Stage – data entry and management are ongoing leveraging the electronic 
data capture system and secured database. 
• Statistical Processing and Data Analysis – is expected to take 1-3 months from the data 
entry of the last patient visit or the last patient enrolled. 
4.5 
Procedures 
The ECG Belt study methodology is composed of: 
• 1 scheduled clinic visits (baseline)   
• 1-week follow-up monitoring period for adverse events (phone call).  
 
Visit 1 – Baseline 
The following activities will be completed at Visit 1 (Baseline): 
• Subjects will be screened to ensure they meet ALL the inclusion criteria and NONE of 
the exclusion criteria. 
• Subjects will sign an Informed Consent form before any of the study related procedures 
are performed. 
• Sequentially ordered subject identification number will be assigned for the specific site.  
• Demographic  
• Medical history  
• Concomitant medication specifically ACE/ARB, beta blockers, diuretics, and anti-
arrhythmics use  
• Relevant co-morbidities will be recorded 
• NYHA Functional Classification 
• Collection of device characteristics and implanted system description. 
• ECG Belt Research System Procedure* 
o LBBP 

 
 
 
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 Native conduction 
 RV pacing if available 
 Bipolar LBBAP 
 Unipolar LBBAP – nonselective and selective (different outputs) 
 Fusion pacing with native conduction at different AV delays 
 
o HOT-CRT 
 Native conduction 
 HBP / LBBAP 
 HOT-CRT 
 AV delay optimization. 
 
o Medtronic Device (pacemaker/ICD)  based Holter recording during the ECG 
belt recording** 
• 12-lead ECG (Rhythm Strips) 
• Adverse Events related to ECG Belt 
*The use of the ECG Belt Research System may add approximately 40 minutes of time to follow-up 
visits for testing parameters, plus 10 minutes for the application of the ECG Belt and System set-up.  
**The DR220 Digital Recorder (NorthEast Monitoring, Inc, MA, USA) is a Holter monitor that is 
designed to facilitate the ambulatory cardiac monitoring and is intended for use with Medtronic System-B 
compatible implantable pulse generators, implantable cardiac defibrillators, and cardiac resynchronization 
therapy devices and implantable cardiac monitors. The Holter monitor will be used in accordance with its 
labeling. Only trained study personnel should apply the monitors. The data obtained by monitoring is not 
analyzed at the time of the recording. After the recording is complete, the data must later be returned and 
analyzed at Medtronic. No personal information will be entered and collected by DR220 recorder.  
For the purposes of this study, the Holter will be used during the in-office monitoring and will be 
removed at the conclusion of the monitoring. Each patient will have one DR220 Holter monitors collected 
during the study.  
The Holter Recorder has application for any subject with a Medtronic IPG. For the purposes of this study, 
the intended use of the Holter Recorder is to acutely uplink continuous EGM signals that will be collected 
by the IPG in Holter mode.  
 
 
 

 
 
 
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Monitoring (Scheduled Follow-up) 
Total period of 1 week (+/- 5 days) starting after baseline visit, during which the subject will be 
contacted by phone to assess any adverse events related to the ECG Belt. Patients will be 
followed in the device clinic as per standard of care.  
 
Study Exit 
Once the 1-week follow-up is completed, the subject is considered exited from the study, unless 
there is unresolved system related AEs with further actions or treatments planned. 
 
4.5.1 Schedule of Events 
 
Clinic 
Phone 
Clinic 
 
Visit 
 
Visit 1 – Baselinea 
 
Week 1 F/U 
 
 
Unscheduled d  
 
Visit Window 
 
Day 0 
 
(+/-5 days) 
 
 
Medical Records Review 
 
X 
 
 
Informed Consent 
X 
 
 
Inclusion/Exclusion 
X 
 
 
Medical History  
X 
 
 
Demographics 
X 
 
 
Concomitant Medication e 
X 
 
 
NYHA Functional Classification 
X 
 
 
Device interrogation 
 
X 
 
 
ECG Belt System procedure c 
X 
 
 
ECG 12 Lead 
X 
 
 
Adverse Events/ SAE b 
 
X 
X 
 

 
 
 
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a- Potential patients will be identified by clinician referrals. All patients will share same recruitment 
process and procedures 
b- Only adverse event related to the use of the ECG Belt and/or device malfunctions 
c- The use of the ECG Belt Research System might add approx. 40 minutes of time to f/u visits for 
testing parameters, plus 10 min for system set up.  
d- When 1-week f/u is completed, subject is considered exited from the study unless unresolved 
system related AEs occur. An unscheduled follow-up visit may be required. 
e- Special attention to:  ACE/ARB, beta blockers, diuretics, and anti-arrhythmic use  
 
4.6 
Primary Endpoints 
The primary endpoints will be  
• ECG Belt analysis of Standard Deviation of Activation Times (SDAT) of LBBAP 
compared to native conduction 
• ECG belt analysis of Left Ventricular activations times (LVAT) of LBBAP compared to 
baseline 
• ECG belt analysis of SDAT and LVAT of HOT-CRT compared to baseline 
• ECG belt analysis of QRS duration at baseline compared to various LBBAP options 
• Comparison of above parameters of LBBP to historic biventricular or RV pacing  
4.7 
Secondary Endpoints 
There are no secondary endpoints. 
 
4.8 
Statistics 
Summary tables of descriptive statistics will be provided for all variables. Continuous variables 
will be summarized using means and standard deviations or median and interquartile ranges 
(IQR), depending on distributional assumptions. Categorical variables will be summarized using 
percentage and frequency counts. The descriptive statistics will be reported for Baseline and 
follow-up (adverse events only will be collected). 
Analysis of the following objectives will be accomplished using the Chi-square or Fisher’s exact 
tests, and T-tests or non-parametric test (Median test, Wilcoxon rank sum test, etc.), as 
appropriate. 

 
 
 
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• To assess ECG Belt derived native conduction parameters and compare them to LBBAP 
and HOT-CRT.  
o ECG Belt analysis of Standard Deviation of Activation Times (SDAT) of LBBAP 
compared to native conduction 
o ECG belt analysis of Left Ventricular activations times (LVAT) of LBBAP 
compared to baseline 
o ECG belt analysis of SDAT and LVAT of HOT-CRT compared to baseline 
• These ECG belt characteristics will be compared with historic ECG belt parameters 
obtained for right ventricular pacing/ Biventricular pacing in prior studies 
 
This study is information gathering and not designed to perform any hypothesis testing. 
Therefore, any results of statistical tests performed are not conclusive but used to design a larger 
prospective study.  
4.9 
Data Management 
4.9.1 Data Collection and Storage 
Data will be collected by research team members, and the resulting analytic file will be stored in 
a password-protected database on Geisinger’s secure network. Only research team members can 
access the data file. The research team members will review the charts and gather all the needed 
information. The research team plans to perform manual chart reviews to access any required 
data elements.  
 
The following data, including relevant dates, will be collected: 
• Medical record number 
• Date of birth/date of death 
• Information relevant to all encounters, admissions/discharges, clinical procedures, 
medications administered, problem list entries, and lab values 
• Baseline demographic variables of patients (age, sex, ethnicity, tobacco use, 
comorbidities) 
• Clinical outcomes and procedural related complications  
 

 
 
 
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All identifiable date will be stored on a secure server in password protected files.  Any hard copy 
data will be secured in a locked (area/suite/drawer/cabinet), if applicable.  Only aggregate data 
(i.e., no PHI) will be shared with the Sponsor.   
 
4.9.2 Records Retention 
Records of data generated during the study shall be retained for at least 6 years and could be used 
for future research studies submitted and approved by the IRB. 
 
5 
SAFETY MONITORING  
The non-invasive ECG Belt Research System is investigational but has been qualified for human 
use and tested for safety similar to standard ECG recording systems. There may be skin redness 
or irritation from the additional ECG Belt electrodes, minor pain or discomfort while attaching 
and detaching multiple electrodes to the skin, and discomfort due to lying on the ECG Belt. 
Since a larger surface is covered by the ECG Belt, the area of skin redness or irritation may be 
larger than with standard ECG electrode systems. There may be additional risks related to use of 
the ECG Belt Research System that are unknown at this time. 
 
Lastly, we expect patient condition to vary over time. Changes in the patient medical condition 
in the context of this study is not an adverse event unless directly related to the use of the ECG 
Belt. 
5.1 
Adverse Event Reporting 
Patients will be asked about adverse events related to the use of the ECG Belt.  These data will 
not be monitored in real time and patients will be educated on the need to contact their physician 
directly should they have any medical concern. 
 
Only ECG Belt related SAE/AE’s will be collected and reported and then assessed if it is device 
related. 
 

 
 
 
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5.2 
Other Reportable Information.  
Geisinger will notify Medtronic and regulatory authorities as applicable for the following 
incidents immediately upon learning of them: 
• Any malfunction or deterioration in the characteristics and/or performance of the 
investigational device, as well as any inadequacy in the labeling or instructions 
for use which led or might have led to the death or serious deterioration in the 
state of health of a patient, user, or other person. 
• Any technical or medical reason resulting in withdrawal of a device from the 
market by the manufacturer. 
• An adverse event that led to death. 
• An adverse event that led to a serious deterioration in the state of heath that either 
resulted in: 
o Life-threatening illness or injury 
o Permanent impairment of a body function or permanent damage to a body 
structure 
o A condition necessitating medical or surgical intervention to prevent 
permanent impairment of a body function or permanent damage to a body 
structure. 
 
6 
PROTECTION OF HUMAN SUBJECTS 
6.1 
Informed Consent and HIPAA Authorization 
This clinical study will comply with HIPAA. Specifically, the electronic database that will be 
utilized for the collection of the clinical data that is mandated by this protocol (including 
personal identifiable information and protected health information) will be HIPPA compliant.  
The informed consent will be approved by the IRB and will include the appropriate language that 
will obtain research participants’ authorization for use/disclosure of the information for research 
purposes (per 45 CFR 164.512(i)(1)(i) (HIPAA)) including the right of the subjects to revoke 

 
 
 
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their consent/authorization as well as disclose his/her right to access the research information 
(per 45 CFR 164.508 (b) (5) and 164.528). 
The investigator will provide for the protection of the subjects by following all applicable 
regulations.  The informed consent/authorization form will be submitted to the IRB for review 
and approval.   
Before any procedures specified in this protocol are performed, a subject must: 
• Be informed of all pertinent aspects of the study and all elements of informed consent.  
• Be given time to ask questions and time to consider the decision to participate. 
• Voluntarily agree to participate in the study.  
• Sign and date an IRB-approved informed consent form. 
 
6.2 
Protection of Human Subjects Against Risks 
All electronic study data will be kept in password-protected computer files, and hard copy data 
will be stored in a locked environment that is only accessible only to the study team members.  
Data will be coded by assigning a unique study identification number to subjects’ medical record 
numbers.  Analysis will be performed using the coded data.  Only aggregate data without 
personal identifiers will be included when presenting results or submitting manuscripts for 
publication. 
 
 
7 
PUBLICATION PLAN   
We plan to submit a scientific abstract to upcoming meetings and to publish the data as a 
manuscript in a peer-reviewed journal. 
 
 
 
 

 
 
 
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8 
REFERENCES
 
1 Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the 
Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay. A 
Report of the American College of Cardiology/American Heart Association Task Force on 
Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 
2018;0:CIR.0000000000000628. 
 
2 Huang W, Su L, Wu S, Xu L, Xiao F, Zhou X, Ellenbogen KA. A Novel Pacing Strategy With Low and 
Stable Output: Pacing the Left Bundle Branch Immediately Beyond the Conduction Block. Can J 
Cardiol. 2017 Dec;33(12):1736.e1-1736.e3. doi: 10.1016/j.cjca.2017.09.013. 
 
3 Vijayaraman P, Huang W: Atrioventricular Block at the Distal His Bundle: Electrophysiological 
Insights from Left Bundle Branch Pacing. Heart Rhythm Case Reports 2019. 
https://doi.org/10.1016/j.hrcr.2019.01.006 
 
 
 
4 Gage, RM,.Curtin,AE,  Burns,KV, et al. Changes in electrical dyssynchrony by body surface 
mapping predict left ventricular remodeling in patients with cardiac resynchronization 
therapy. Heart Rhythm 2017;14:392–399. 

 
 
 
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