Intra-procedural Transthoracic EChocardiogram to Facilitate LBBAP
Phase: NA
Conditions: Heart Failure
Sponsor: Geisinger Clinic

CONFIDENTIAL AND PROPRIETARY
1
Research Protocol – 2022-0917
Intra-procedural Transthoracic EChocardiogram to facilitate LBBAP (EC-LBBAP study) 
Version: 1.1
11 April 2023
Version: 2.0                            6 March 2024
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
Resources
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PROTOCOL SIGNATURE PAGE
All necessary sponsor personnel and/or designees have reviewed and approved the Intra- 
procedural Transthoracic Echocardiogram to facilitate LBBAP (EC-LBBAP) study 
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
Printed Name of Signer
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
Printed Name of Primary Investigator
Regional Director, Cardiac Electrophysiology, Geisinger Northeast
Title 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
4.6
Primary Endpoints.......................................................................................................10
4.7
Secondary Endpoints...................................................................................................11
4.8
Statistics ......................................................................................................................11
4.9
Data Management .......................................................................................................11
4.9.1
Data Collection and Storage.........................................................................11
4.9.2
Records Retention.........................................................................................12
5
SAFETY MONITORING.....................................................................................................12
5.1
Adverse Event Reporting............................................................................................12
5.2
Other Reportable Information. ....................................................................................13
6
PROTECTION OF HUMAN SUBJECTS ...........................................................................13
6.1
Informed Consent and HIPAA Authorization.............................................................13
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6.2
Protection of Human Subjects Against Risks..............................................................14
7
PUBLICATION PLAN ........................................................................................................14
8
REFERENCES .....................................................................................................................15
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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 and others3-7 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.8 Additionally, LBBAP has been shown to be safe, feasible 
and effective in patients with AV block and superior to right ventricular pacing in observational 
case-controlled studies.7 The potential advantage of this method is several fold:3 1. Bypass the
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site of conduction block in patients with infranodal AV block and LBBB (even in patients where 
His bundle pacing fails to correct the LBBB) 2. Achieve low capture threshold with excellent 
sensing 3. Obtain LV endocardial pacing in addition to conduction system pacing without a lead 
in the LV endocardial cavity.
The success of LBBAP has been variable between 80-90% based on several observational 
studies and Geisinger experience. The procedural duration and fluoroscopy duration for LBBAP 
is somewhat longer than traditional right ventricular pacing. Left bundle branch area pacing 
(LBBAP) can be challenging in patients where the sheath cannot be oriented perpendicularly to 
the septum. In some patients, the lead may advance deep into the septum in a tangential fashion. 
Existing methods have limitations in assessing the exact depth of the lead in the septum and 
proximity to the LV endocardial surface. We hypothesize based on our early experience that 
transthoracic echocardiogram including hand-held echo can be helpful in most of the above 
scenario to both facilitate successful implantation and assessment of the lead location during the 
implantation and possibly reduce the fluoroscopy duration.
3
OBJECTIVES
3.1
General Objective
The objective of the study is to assess the utility of intraprocedural transthoracic echocardiogram 
to facilitate successful LBBAP.
3.2
Specific Objective
To assess the success rate of intraprocedural transthoracic echocardiogram guided 
LBBAP lead implantation.
To develop a work-flow and define echocardiography windows to achieve successful 
LBBAP
To demonstrate reduction in fluoroscopy and procedural duration for LBBAP.
To assess the success rates of using hand-held echo probe to achieve LBBAP
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4
STUDY DESIGN
4.1
Description
The EC-LBBAP study is a prospective, single-center, observational research study. The study 
team will identify all patients who satisfy the inclusion and exclusion criteria. The study team 
will evaluate the feasibility and success rates of echocardiogram guided LBBAP lead 
implantation.
Eligible patients would undergo 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 
2D transthoracic echo at implant.
During implant procedure, transthoracic echo windows will be identified and documented: 
Parasternal short and long axis, apical 2 and 4 chamber views and subcostal views to visualize 
the proximal interventricular septum. Following venous access using cephalic vein cut-down or 
ultrasound guided axillary vein access, the lead implantation in the left bundle branch region will 
be guided by echocardiography.
Retrospectively, the study team will identify 30 consecutive previous patients who satisfy 
inclusion and exclusion criteria (control patients). The study team will compare the difference in 
procedural success between Case and Control patients.
4.2
Study Population
4.2.1
Approximate Number of Subjects
Approximately 30  patients will participate in the EC-LBBAP study to be conducted at Geisinger 
Heart Institute.
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All patients will share the same recruitment process, inclusion and exclusion criteria and same 
surgical procedure. Twenty patients will undergo intraprocedural transthoracic echocardiogram via 
standard practices. An additional 10 patients will undergo intraprocedural transthoracic 
echocardiogram using a hand-held ultrasound device.
4.2.2
Inclusion Criteria
The following is the inclusion criteria for the EC-LBBAP study:
1. Patients > 18 years of age
2. Patient with an indication for permanent pacemaker or ICD utilizing conduction system 
pacing lead for bradycardia or cardiac resynchronization therapy
3. Patient is willing to comply with all study procedures and be available for the duration of 
the study.
4.2.3
Exclusion Criteria
The following patients or situations are excluded in the EC-LBBAP 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. 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 3 months (+/- 1 week). This includes a 
monitoring (follow up) period which starts immediately after signing the Informed Consent and 
completing the baseline visit (visit 1).
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4.4.2
Approximate Duration of Study
This study will be completed in approximately 18 to 24 months duration. The end of the EC- 
LBBAP 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 30  patients from Geisinger Heart Institute 
is expected to take 15-18 months based on enrollment rate of 1 to 3 subjects per month.
Monitoring Stage – based on the planned 3 month monitoring period for each patient, last 
patient completed is expected 10-12 months from the study beginning.
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 EC-LBBAP study methodology is composed of:
1 scheduled clinic visits (baseline)
2-week follow-up monitoring period for device evaluation and adverse events (device 
clinic visit).
3-Month follow-up/exit visit for device evaluation and adverse events (device clinic visit).
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.
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
Subjects will sign an Informed Consent form before any of the study related procedures 
are performed.

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.

EC-LBBAP research procedure *
Intraprocedural transthoracic echocardiogram* 
Fluoroscopy duration for LBBAP lead implantation 
Procedural duration for LBBAP lead implantation 
Total fluoroscopy duration
Total procedural duration 
Success of LBBAP

12-lead ECG (Rhythm Strips)

Adverse Events related to echocardiogram
*The use of the EC-LBBAP may add approximately 15 minutes of time for total procedure but 
may lower the fluoroscopy and procedure duration for LBBAP lead implantation. Additionally, 
this may improve the safety and success of the procedure.
Monitoring (Scheduled Follow-up - Visit 2)
Total period of 2 week (+/- 1 week) starting after baseline visit, during which the subject will be 
seen in device clinic for routine follow-up to assess device function and to assess any adverse
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events related to the study. Patients will subsequently be followed in the device clinic as per 
standard of care.
Study Exit (Visit 3)
Once the 3-month 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.
4.6
Primary Endpoints
The primary endpoints will be

Success rate of LBBAP utilizing intraprocedural transthoracic echocardiogram

Reduction in fluoroscopy/procedure duration for LBBAP lead implantation compared to 
historic data from prior Geisinger studies utilizing LBBAP

Identification of work-flow and echocardiographic windows to facilitate LBBAP
4.7
Secondary Endpoints
The secondary outcomes will be as follows:
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 above endpoints 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.
This study is information gathering and designing workflow. Therefore, any results of statistical 
tests performed are not conclusive but used to design a larger prospective study.
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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
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
Echocardiogram is routinely used in clinical practice and is associated with minimal adverse 
events related to ultrasound gel use on the skin. Rare skin irritation or erythema may be noted. 
No significant adverse events are anticipated as several thousand ultrasound-based procedures 
are performed each year in the Geisinger Health System.
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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 
intraprocedural echocardiogram.
5.1
Adverse Event Reporting
Patients will be asked about adverse events related to the use of the echocardiography. 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 echocardiogram related adverse event will be collected and reported and then assessed if it 
is procedure related.
5.2
Other Reportable Information.
Geisinger will notify Medtronic and regulatory authorities as applicable for the following 
incidents immediately upon learning of them:

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.
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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 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.
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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.
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. Vijayaraman P, Subzposh FA, Naperkowski A, Panikkath R, John K, Mascarenhas V, Bauch 
TD, Huang W. Prospective evaluation of feasibility and electrophysiologic and 
echocardiographic characteristics of left bundle branch area pacing. Heart Rhythm. 2019 
Dec;16(12):1774-1782. doi: 10.1016/j.hrthm.2019.05.011. Epub 2019 May 25. PMID: 
31136869.
5. Vijayaraman P, Cano Ó, Koruth JS, Subzposh FA, Nanda S, Pugliese J, Ravi V, Naperkowski 
A, Sharma PS. His-Purkinje Conduction System Pacing Following Transcatheter Aortic Valve 
Replacement: Feasibility and Safety. JACC Clin Electrophysiol. 2020 Jun;6(6):649-657. doi: 
10.1016/j.jacep.2020.02.010. Epub 2020 May 6. PMID: 32553214.
6. Huang W, Chen X, Su L, Wu S, Xia X, Vijayaraman P. A beginner's guide to permanent left 
bundle branch pacing. Heart Rhythm. 2019 Dec;16(12):1791-1796. doi: 
10.1016/j.hrthm.2019.06.016. Epub 2019 Jun 22. PMID: 31233818.
7. Sharma PS, Patel NR, Ravi V, Zalavadia DV, Dommaraju S, Garg V, Larsen TR, 
Naperkowski AM, Wasserlauf J, Krishnan K, Young W, Pokharel P, Oren JW, Storm RH, 
Trohman RG, Huang HD, Subzposh FA, Vijayaraman P. Clinical outcomes of left bundle branch
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area pacing compared to right ventricular pacing: Results from the Geisinger-Rush Conduction 
System Pacing Registry. Heart Rhythm. 2021 Sep 3:S1547-5271(21)02102-0. doi: 
10.1016/j.hrthm.2021.08.033. Epub ahead of print. PMID: 34481985.
8. Huang W, Wu S, Vijayaraman P, Su L, Chen X, Cai B, Zou J, Lan R, Fu G, Mao G, 
Ellenbogen KA, Whinnett ZI, Tung R. Cardiac Resynchronization Therapy in Patients With 
Nonischemic Cardiomyopathy Using Left Bundle Branch Pacing. JACC Clin Electrophysiol. 
2020 Jul;6(7):849-858. doi: 10.1016/j.jacep.2020.04.011. PMID: 32703568.
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IRB NUMBER: 2022-0917
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