His Bundle Pacing Versus Coronary Sinus Pacing for Cardiac Resynchronization Therapy
Phase: NA
Conditions: Congestive Heart Failure
Sponsor: University of Chicago

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Version:  2019Dec09 
PROTOCOL TITLE:  
HIS BUNDLE PACING VERSUS CORONARY SINUS PACING FOR CARDIAC RESYNCHRONIZATION 
THERAPY  
PI: GAURAV A. UPADHYAY, MD AND RODERICK TUNG, MD 
CO-I(S): HEMAL NAYAK, MD; MICHAEL BROMAN, MD PHD; CEVHER OZCAN, MD; ANDREW 
BEASER, MD; ZAID AZIZ, MD 
FUNDING: INTERNAL 
SPONSOR: NONE 
TYPE OF RESEARCH: CLINICAL TRIAL 
INTERVENTION: IMPLANTATION OF CARDIAC RESYNCHRONIZATION THERAPY DEVICE 
MANUFACTURER OF INTERVENTION: NOT APPLICABLE 
IND OR IDE # NOT APPLICABLE 
NCT Number: NCT02700425

 
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Version:  2019Dec09 
 
Contents 
1.  Introduction ................................................................................................................................ 6 
A. 
Background and Rationale ............................................................................................... 6 
B. 
Objectives ......................................................................................................................... 7 
2.  Study Design .............................................................................................................................. 7 
3.  Subject Selection and Withdrawal ............................................................................................. 8 
4.  Study Device ............................................................................................................................ 10 
5.  Study Procedures ..................................................................................................................... 10 
6.  Statistical Plan and Considerations .......................................................................................... 12 
7.  Risks and Benefits .................................................................................................................... 12 
8.  Safety and Adverse Events ...................................................................................................... 13 
9.  Data handling and Record Keeping ......................................................................................... 13 
10.  Study Monitoring, Auditing and Inspecting .......................................................................... 13 
11.  Financial Considerations ........................................................................................................ 13 
12.  Ethical Considerations ........................................................................................................... 13 
13.  Conflict of Interest ................................................................................................................. 13 
14.  References .............................................................................................................................. 14 
A. 
Questionnaire ................................................................................................................. 16 
B. 
Schedule of Events (schema) ......................................................................................... 17 
 
 

 
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Version:  2019Dec09 
STUDY SUMMARY 
TITLE  
His-bundle pacing versus coronary sinus pacing for 
cardiac resynchronization therapy (CRT) 
SHORT TITLE 
The His-Sync Study 
PROTOCOL NUMBER  
UofC & Baptist Health Louisville: IRB15-1728 
UCLA: IRB#15-000464 
NWU: STU00202920 
Geisinger: 2017-0339 
IU: 1707220499 
Rush: 16100902-IRB01 
Edward:  HIS-SYNCH 
METHODOLOGY 
Single-blind clinical trial 
STUDY DURATION  
12 months 
STUDY CENTER(S) 
Multi-center; also enrolling patients at the University of 
California Los Angeles (UCLA) Medical Center, 
Northwestern University (NWU), Geisinger Wyoming 
Valley Medical Center (Geisinger), Indiana University 
(IU), Rush University Medical Center (Rush), Edward 
Hospital (Edward), and Baptist Health Louisville 
OBJECTIVES 
To compare the effectiveness of his-bundle pacing versus 
coronary sinus LV lead localization in patients with heart 
failure. 
NUMBER OF SUBJECTS  
40 patients total 
DIAGNOSIS AND MAIN INCLUSION 
CRITERIA 
Patients with heart failure (HF) eligible for CRT as part of 
routine standard-of-care based on accepted Class I or Class 
II indications will be considered for this study. Inclusion 
criteria include: 
1) Left ventricular ejection fraction (LVEF) ≤ 35%, sinus 
rhythm (SR), left bundle-branch block (LBBB) 
morphology, and QRS duration ≥ 150 msec, and 
NYHA Class II, III, or ambulatory Class IV patients on 
goal-directed medical therapy (GDMT) [Class I] 
2) LVEF ≤ 35%, SR with LBBB with QRS 120-149 msec 
on GDMT [Class IIa] 
3) LVEF ≤ 35%, SR with non-LBBB with QRS ≥ 150 
msec on GDMT [Class IIa] 
4) LVEF ≤ 35%, in AF if medication or AV nodal ablation 
will allow near 100% pacing [Class IIa] 
5) LVEF ≤ 35% undergoing new or replacement device 
with anticipated >40% ventricular pacing on GDMT 

 
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Version:  2019Dec09 
[Class IIa] 
6) LVEF ≤ 30%, ischemic etiology of HF, SR with LBBB 
≥ 150 msec and NYHA Class I symptoms on GDMT 
[Class IIb] 
7) LVEF ≤ 35%, SR with non-LBBB with QRS 120-149 
msec, NYHA Class III/ambulatory Class IV HF on 
GDMT [Class IIb] 
8) LVEF ≤ 35%, SR with non-LBBB with QRS ≥ 150 
msec, NYHA Class II HF on GDMT [Class IIb] 
STUDY PRODUCT  
His-Bundle lead placement will require use of Medtronic 
delivery sheath (C315 HIS, Medtronic, Minneapolis, MN) 
and pacemaker lead (Select Secure 3830, Medtronic, 
Minneapolis, MN) for patients randomized to His bundle 
pacing. These are FDA approved for routine clinical use. 
 
Coronary sinus LV leads utilized in the study will be FDA 
approved leads per the discretion of the implanting 
physician 
DURATION OF ADMINISTRATION  
Pacing will be delivered throughout the duration of the 
study, with goal pacing delivery of 95%, as is the standard-
of-care for patients receiving CRT 
REFERENCE THERAPY  
The reference therapy will be the control group; i.e., those 
patients assigned to CRT with use of a CRT 
STATISTICAL METHODOLOGY  
Traditional statistical methods will be employed. The 
student’s T-test will be used for continuous comparisons. 
Fisher’s exact or the Chi-square test will be applied for 
dichotomous variables. Time to endpoint analysis will be 
performed using the Kaplan-Meier method. 
 

 
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Version:  2019Dec09 
LIST OF ABBREVIATIONS 
 
ACE-I  
 
ANGIOTENSIN-CONVERTING ENZYME INHIBITOR 
AF 
 
 
ATRIAL FIBRILLATION 
ARB  
 
ANGIOTENSIN RECEPTOR BLOCKER 
BB 
 
 
BETA-BLOCKER 
CRT 
 
 
CARDIAC RESYNCHRONIZATION THERAPY 
CS 
 
 
CORONARY SINUS 
FDA  
 
FOOD AND DRUG ADMINISTRATION 
GDMT 
 
GOAL-DIRECTED MEDICAL THERAPY 
HBP 
 
 
HIS BUNDLE PACING 
HF 
 
 
HEART FAILURE 
ICD 
 
 
IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR 
IRB 
 
 
INSTITUTIONAL REVIEW BOARD 
LBBB  
 
LEFT BUNDLE-BRANCH BLOCK 
LV 
 
 
LEFT VENTRICULAR 
LVEF  
 
LEFT VENTRICULAR EJECTION FRACTION 
NYHA  
 
NEW YORK HEART ASSOCIATION 
RA 
 
 
RIGHT ATRIUM 
RBBB  
 
RIGHT BUNDLE-BRANCH BLOCK 
RV 
 
 
RIGHT VENTRICLE 
SR 
 
 
SINUS RHYTHM 
TTE 
 
 
TRANSTHORACIC ECHOCARDIOGRAM 
UCMC 
 
UNIVERSITY OF CHICAGO MEDICAL CENTER 
UOFC  
 
UNIVERSITY OF CHICAGO 
VF 
 
 
VENTRICULAR FIBRILLATION 
VT 
 
 
VENTRICULAR TACHYCARDIA 
 
 

 
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Version:  2019Dec09 
1.  INTRODUCTION  
 
A. BACKGROUND AND RATIONALE 
 
Heart failure has been characterized as the singular epidemic of contemporary 
cardiovascular medicine. At 40 years of age, the lifetime risk of developing heart failure is one in 
five.1 The prevalence of heart failure exceeds 5.3 million in the United States, and accrued 
estimated direct and indirect costs totaling $39.2 billion in 2010.1,2 During the past two decades, 
cardiac resynchronization therapy (CRT) has emerged as a safe and efficacious device-based 
therapy for heart failure patients with severe systolic dysfunction and intraventricular conduction 
delay.3-5 CRT is the use of a pacemaker with three electrical leads to coordinate myocardial 
contraction. Two leads are endocardial, placed in the right atrium (RA) and right ventricle (RV), 
while a third lead is traditionally placed in a tributary of the coronary sinus overlying the 
epicardial surface of the left ventricle (LV). CRT exerts its physiological impact via 
synchronizing ventricular contraction, leading to improved left ventricular filling, and pumping 
efficiency. Multiple prospective randomized studies have shown that CRT yields long-term 
clinical benefits, including improved quality of life, increased exercise capacity, reduced heart 
failure hospitalization and decreased all-cause mortality.6-11  
 
Despite dramatic impact and expanding indications, however, there remain significant 
barriers to realizing the overall potential benefit of CRT. Most notably, up to one-third of 
patients treated with CRT do not derive any detectable clinical or echocardiographic benefit, and 
indeed, some worsen after resynchronization.3,12 Intrinsic patient and myocardial substrate 
characteristics a priori may limit response in some patients. Additionally, intraprocedural 
factors–particularly the location of the left ventricular (LV) lead–may also effect longer term 
outcome. In particular, recent analysis from MADIT-CRT and other studies showed that an LV 
lead placed in an anatomically apical region of the heart is associated with a worse clinical 
outcome.13,14 Distinct and complementary to anatomical localization, characterization of the LV 
lead with respect to the heart’s electrical activation pattern has been shown to be an important 
determinant of response.15-18 Effective integration of anatomical and electrical data in order to 
guide LV lead placement for CRT is still actively being explored.  
 
More recently, the feasibility of resynchronizing ventricular activation by permanent 
pacing of the His bundle region has been described, with clear clinical advantages over 
traditional RV apical pacing.19-23 This technique is an FDA approved therapy for pacing. The 
physiologic benefit of permanent His bundle pacing (HBP) is the ability to stimulate the 
ventricles through the intrinsic His-purkinje system, which results in synchronous electrical and 
mechanical activation. Furthermore, similar to CRT, reports of hyper-response—typically 
described as patient functional recovery to an LVEF ≥ 50%, has been reported with HBP after 
restoration of normal intrinsic conduction.24-26 Perhaps even more provocatively, in a recent 
study in which patients were implanted with four leads (RA, RV, CS LV lead, and HBP lead), 
both modes of resynchronization (HBP and CS) were studied utilizing a cross-over design, and 
both were found to be associated with similar benefit (with patients acting as their own 
controls).27 Indeed, HBP may have theoretical advantages over CRT using a coronary sinus lead, 
which is associated with limited coronary venous anatomy and complications that include 
coronary sinus dissection, venous perforation, and the potential for proarrhythmia. While both 
techniques comprise the standard-of-care for pacing, direct comparison of HBP with traditional 

 
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Version:  2019Dec09 
CS lead position for CRT has not yet been investigated, and is the motivation behind the His-
SYNC Study. 
 
B. OBJECTIVES  
 
We hypothesize that: 
a. In patients with advanced heart failure and evidence of intraventricular conduction delay 
who meet criteria for CRT, HBP may be safely achieved and 
b. HBP is associated with similar echocardiographic and clinical outcome as conventional 
CS pacing during CRT 
 
Specific aims: 
Aim 1: To determine the overall rate of successful His-bundle lead placement at the time of 
implant of CRT. Patients randomized to HBP but who cannot be successfully implanted with a 
HBP lead will cross-over to traditional CS lead position. 
 
Aim 2: To assess the impact of HBP versus CS pacing on acute and mid-term outcomes. 
Acute outcomes include incidence of periprocedural complication and change in QRS duration 
pre-and post-pacing. Mid-term outcomes include echocardiographic response at 6 and 12 months 
along with a composite clinical outcome of heart failure hospitalization, arrhythmia, and all-
cause mortality. 
 
2.  STUDY DESIGN  
 
Study design: Single-blind study. Patients will be randomized, at the time of implant, to HBP 
versus CS pacing, and remain blinded to their treatment allocation. Both treatment options use 
standard-of-care, FDA-approved devices. The distinction is only in the allocation toward HBP 
and CS pacing. Treating physicians will be aware of assignment in order to facilitate routine 
device follow-up. Echocardiographic and electrocardiographic evaluation will also be performed 
in a blinded manner. 
 
Cross-over is permitted between treatment group allocation if: 
- 
CS lead cannot be placed due to difficult cannulation of the CS, limited branches at the 
posterolateral or lateral wall, or phrenic nerve capture. These patients may then cross-
over to HBP. 
- 
HBP patients may cross-over if lead cannot be positioned with adequate stability and 
reasonable pacing output or if QRS width does not narrow by at least 20% or to a QRS 
width of ≤ 130 msec. 
 
Implant procedure will be per routine percutaneous access, as is standard for pacemaker and 
ICDs. All patients will receive an FDA-approved cardiac resynchronization therapy pacemaker 
or defibrillator device, as per standard of care outlined for the patient. In order to facilitate 
optimal lead placement, arterial access for levo-phase CS angiography and/or LV septal mapping 
to characterize site of bundle-branch block may also be performed, at the discretion of the 
implanting physician per his/her standard practice. 
 

 
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Version:  2019Dec09 
Follow-up will be performed at 2 weeks post-implant for incision check and device interrogation 
as is standard of care. In addition, routine device and clinical follow-up will be scheduled at 1, 3, 
6, and 12 months.  
 
Electrocardiography (i.e., ECG) will be performed pre-implant, prior to hospital discharge, at 3 
months, 6 months, and 12 months. Echocardiography will be performed pre-implant, 6 months, 
and  12 months to evaluate for change in LVEF, chamber dimension, and wall motion with strain 
imaging as is standard of care in the treatment of patients with advanced heart failure. NYHA 
functional class and quality of life (utilizing the Kansas City Cardiomyopathy Questionnaire) 
will be assessed pre-implant and at 6 months. 
 
Duration of study: 12 months 
 
Primary endpoints: A combination of clinical, electrocardiographic, and echocardiographic 
endpoints will be prospectively studied. These include: 
- 
Clinical: Primary clinical endpoint is a composite of heart failure hospitalization, VT/VF, 
and any-cause mortality at 12 months. 
- 
Electrocardiographic: Change in QRS duration between pre-implant and at hospital 
discharge, 3 months, 6 months, and 12 months will be performed by readers blinded to 
treatment allocation. Arrhythmia occurrence (i.e., AF, nonsustained VT, VT or VF 
requiring device therapy) will be documented throughout the study period 
- 
Echocardiographic: Change in left ventricular ejection fraction, chamber dimension, 
and tissue-strain pre-implant, at 6 months, and at 12 months to be performed by readers 
blinded to treatment allocation 
 
Primary safety endpoint: Procedure-related complications will be assessed prospectively both 
acutely and throughout the study period, including:  
- 
Procedure related: pneumothorax, perforation, pericardial effusion, or hemorrhage  
- 
System related: implant site hematoma, implant site infection 
- 
Lead related: lead dislodgement, lead fracture, inability to pace due to high threshold, 
phrenic capture  
 
Randomization scheme: Patients will be allocated to HBP or standard CS lead at time of implant. 
Patients with LBBB and non-LBBB will be assigned to separate blocks and randomized 
separately. 
 
3.  SUBJECT SELECTION AND WITHDRAWAL  
 
Sites: 
Subjects selected for study will be recruited from eight sites: The University of Chicago Medical 
Center (Chicago, IL), the Ronald Reagan UCLA Medical Center (Los Angeles, CA), 
Northwestern University’s Northwestern Memorial Hospital (Chicago, IL), Geisinger Cardiology 
of the Geisinger Health System (Wilkes-Barre, PA), Indiana University Krannert Institute of 
Cardiology (Indianapolis, IN), Rush University Medical Center (Chicago, IL), Edward Elmhurst 
Healthcare Edward Hospital (Naperville, IL), Baptist Health Louisville (Louisville, KY). Each 
site will function independently but follow the same treatment protocol. Each site will maintain 

 
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Version:  2019Dec09 
their own randomization schedule. The data from the UCLA, NWU, Geisinger, IU, Rush, 
Edward, and Baptist Health sites will be shared with the University of Chicago at study 
completion for data analysis only. 
 
Baptist Health Louisville has formally requested the University of Chicago IRB to serve as its 
own IRB.  The following individuals from Baptist Health will be engaged the conduct of this 
study in Louisville with the following roles: 
- 
John Mandrola, MD – Principle Investigator 
- 
Vicky Swift, APRN – Sub-Investigator 
- 
Teresa Watkins, RN – Research Coordinator 
- 
Kathleen English, RN – Research Coordinator 
All of the study team members at Baptist Health have provided their curricula vitae, as well as 
confirmation of appropriate human subjects protection training. 
 
Eligibility: 
Eligible patients will be similar to those previously enrolled in the large randomized controlled 
trials which guide current indications for CRT. This includes: 
- 
Patients at least 18 years of age 
- 
LV systolic dysfunction with LVEF ≤ 35% 
- 
Evidence of intraventricular conduction delay with QRS duration > 120 msec 
- 
NYHA Class II, III, and ambulatory Class IV heart failure with either ischemic or 
nonischemic cardiomyopathy and patients with NYHA Class I symptoms and ischemic 
cardiomyopathy 
 
Inclusion: 
Inclusion criteria are identical to those presently accepted by the American Heart Association 
(AHA)-American College of Cardiology (ACC)-Heart Rhythm Society (HRS) for CRT.28 These 
include: 
1) Left ventricular ejection fraction (LVEF) ≤ 35%, sinus rhythm (SR), left bundle-branch 
block (LBBB) morphology, and QRS duration ≥ 150 msec, and NYHA Class II, III, or 
ambulatory Class IV patients on goal-directed medical therapy (GDMT) [Class I] 
2) LVEF ≤ 35%, SR with LBBB with QRS 120-149 msec on GDMT [Class IIa] 
3) LVEF ≤ 35%, SR with non-LBBB with QRS ≥ 150 msec on GDMT [Class IIa] 
4) LVEF ≤ 35%, in AF if medication or AV nodal ablation will allow near 100% pacing 
[Class IIa] 
5) LVEF ≤ 35% undergoing new or replacement device with anticipated >40% ventricular 
pacing on GDMT [Class IIa] 
6) LVEF ≤ 30%, ischemic etiology of HF, SR with LBBB ≥ 150 msec and NYHA Class I 
symptoms on GDMT [Class IIb] 
7) LVEF ≤ 35%, SR with non-LBBB with QRS 120-149 msec, NYHA Class III/ambulatory 
Class IV HF on GDMT [Class IIb] 
LVEF ≤ 35%, SR with non-LBBB with QRS ≥ 150 msec, NYHA Class II HF on GDMT 
[Class IIb] 
 
 
 

 
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Exclusion: 
Exclusion criteria include: 
- 
Existing CRT device 
- 
Inability of patient capacity to provide consent for themselves either due to medical or 
psychiatric comorbidity 
- 
Pregnancy 
- 
Participation in other trials 
- 
Difficulty with follow-up 
 
No payments will be made to subjects to participate. 
 
4.  STUDY DEVICE  
 
His-bundle lead pacing will be performed with the Medtronic SelectSecure™, Model 3830 lead. 
Delivery of the lead utilizes a deflectable sheath, the Medtronic SelectSite™, Model C304. Both 
devices are FDA approved for the purpose of his-bundle pacing. It is the only device available 
which is presently FDA approved for selective His pacing. 
 
The lead has not been subject to any FDA advisories or recalls. Current lead performance is 
regularly reported and available at: 
http://wwwp.medtronic.com/productperformance/model/3830-selectsecure.html 
 
CS lead and CRT device generator selected for implant will be left to the discretion of the 
operator. Only FDA approved CS leads and CRT generators will be utilized in the study. There 
are five present manufacturers of CS leads and CRT generators: Biotronik, Boston Scientific, 
Medtronic, Sorin, and St. Jude Medical. The University of Chicago utilizes all five vendors, and 
there is no convincing data to suggest the superiority of any one vendor over the others.  
 
5.  STUDY PROCEDURES 
 
Pre-Implant 
- 
Patients will be screened for study 
- 
Pre-implant ECG reviewed (to be performed on day of screening) 
- 
Baseline transthoracic echocardiogram (TTE) reviewed (does not need to be performed 
during inpatient hospitalization; outpatient or outside-hospital TTE report may also be 
performed) 
- 
Patients who screen-in will be provided Kansas City Cardiomyopathy Questionnaire 
- 
NYHA functional class to be determined by treating physician 
- 
Operating physician will be informed of patient allocation to facilitate planning of 
procedure 
 
Randomization, Implant, and Periprocedure Care 
- 
RA and RV leads will be positioned per routine 
o Arterial access for CS angiography or LV septal mapping may be performed at 
the discretion of the implanting physician in order to facilitate optimal lead 
placement 

 
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- 
 ‘LV’ lead will be positioned in CS or at His-bundle based on allocation assignment 
o The allocation assignment will be based on randomization schedule (developed 
using random number generator) 
o The study coordinator will keep allocations in a sealed envelope and provide to 
implanting physician at time of procedure 
o Patients with LBBB and non-LBBB will be randomized separately 
o Each independent site will maintain their own randomization schedule 
- 
If the initial allocated site is unsuccessful, alternative site will be pursued 
- 
Intracardiac EGM information (surface QRS to LV site or QLV), pacing output, and lead 
position at final site will be recorded 
- 
Predischarge ECG performed 
- 
Predischarge device interrogation will be performed (as per standard of care) 
 
2-Week Incision Check 
- 
As per routine post-device care, all patients will be scheduled for routine postoperative 
device check at 2 weeks to evaluate incision 
- 
Device interrogation (as per standard of care) 
 
1-Month Visit 
- 
Routine device interrogation 
- 
Routine clinical check 
 
(Note:  Week 2 and Month 1 visits may be combined, per treating doctor discretion, for the 
simple post-op wound and clinical visit) 
 
3-Month Visit 
- 
Routine ECG 
- 
Routine device interrogation 
- 
Routine clinical check 
 
6-Month Visit 
- 
Post-implant TTE 
- 
Routine ECG 
- 
Routine device interrogation 
- 
Routine clinical check 
- 
Administration of Kansas City Cardiomyopathy Questionnaire 
- 
NYHA functional class to be determined by treating physician 
 
12-Month Visit 
- 
Post-implant TTE 
- 
Routine ECG 
- 
Routine device interrogation 
- 
Routine clinical check 
- 
Administration of Kansas City Cardiomyopathy Questionnaire 
- 
NYHA functional class to be determined by treating physician 
 

 
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Version:  2019Dec09 
 
Contact between study visits 
- 
Patients will be enrolled in remote device monitoring (as all CRT patients are) and device 
alerts will be monitored per routine 
- 
Any hospitalizations will be flagged for review 
 
Future contact 
- 
Patients will be asked to participate in an extended registry to evaluate longer-term 
clinical outcome after study completion. We will collect data from subjects’ medical 
record for 2 years following their participation in the study. Data collected will include 
cardiac imaging results, and other clinical events such as hospitalization and death. 
 
6.  STATISTICAL PLAN AND CONSIDERATIONS 
 
Sample size estimation: 
The sample size for this study is a total of 40 subjects (20 HBP and 20 CS lead).  The sample 
size estimate was based on a goal to observe an absolute 10% difference in LVEF between the 
two groups, leading to a Cohen’s d statistic of 1. With a significance level (α) = 0.05 and a power 
of 0.8, at least 17 subjects will be required in each group. A goal of 40 subjects was made to 
allow for possible dropout during the study period. 
 
Statistical methods: 
Patients will be studied based on the final treatment allocation. Crossovers and reasons for 
crossover will also be recorded. Fisher’s exact or the Chi-Square test will be used for categorical 
variables, and continuous parameters will be compared by the two-tailed unpaired Student’s t test 
and the F test for analysis of variance (ANOVA), as needed. Kaplan-Meier method will be used for 
computing the event free survival curves. Each implant strategy will be compared within this 
cohort of patients for its impact on percent change QRS duration, LVEF, and as clinical outcome. 
Multiple logistic regression and multiple regressions using the Cox proportional hazards model 
will be performed to determine the independent association of each of the implant variables with 
LVEF and clinical outcome.  
 
7.  RISKS AND BENEFITS 
 
Cardiac resynchronization has led to significant improvement in survival and freedom from HF 
hospitalization for patients with advanced HF and conduction delay. The problem of 
nonresponse remains high, and the goal of this study is to evaluate a possible means to overcome 
nonresponse by varying LV lead position. There are risks with both CS lead position and His-
bundle pacing which include, but are not limited to, the risk for cardiac perforation, tamponade, 
lead dislodgement, fracture, and site infection. Early data27 that two technologies are comparable 
with respect to risk profile. The benefit of identifying an additional suitable location for LV lead 
position would be to extend the benefit of CRT to a broader group of patients. 
 

 
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8.  SAFETY AND ADVERSE EVENTS  
 
Safety: 
As noted above, periprocedural complications will be logged with respect to procedure, system-
related, and lead-related events. Each site’s complications will be independently reviewed at the 
midpoint by the site’s primary investigators. Should there be a trend towards increased 
complication risk, the study will be halted. 
 
Adverse Events: 
As noted above, all adverse events associated with devices will be monitored periprocedurally 
and continuously through the study. The site’s PIs will independently review all events at 
respective sites after randomization of 20 combined subjects in order to make a determination for 
continuance. 
 
9.  DATA HANDLING AND RECORD KEEPING  
 
Data will be collected on paper by study coordinators and transcribed into an electronic database 
which will be maintained on-campus locations at UCLA, NWU, Geisinger, IU, Rush, Edward, 
Baptist Health, and UofC. Data will be managed by the PIs and study coordinators. Access to the 
data will be limited to site PIs and research coordinators only during the study enrollment period.  
All patient specific identifiers will be kept separate from the primary research database. The 
research database will be organized by a unique patient identifier. 
 
10.  STUDY MONITORING, AUDITING AND INSPECTING 
 
All periprocedural complications and adverse events will be reviewed by PIs at study midpoint to 
ensure there is no significant difference in event rate between the study groups. Should there be 
significant differences, or if there should be a high overall event-rate out-of-line with the 
procedural norm for CRT, the study will be halted. 
 
11.  FINANCIAL CONSIDERATIONS 
 
No renumeration will be provided to subjects. 
 
12.  ETHICAL CONSIDERATIONS 
 
No specific ethical considerations are identified in relation to this study. 
 
13.  CONFLICT OF INTEREST 
 
This is an internally funded study with no external support. 
 

 
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Merchant FM, Heist EK, McCarty D, et al. Impact of segmental left ventricle lead 
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16. 
Sassone B, Gabrieli L, Sacca S, et al. Value of right ventricular-left ventricular interlead 
electrical delay to predict reverse remodelling in cardiac resynchronization therapy: the 
INTER-V pilot study. Europace 2010;12:78-83. 
17. 
Sweeney MO, van Bommel RJ, Schalij MJ, Borleffs CJ, Hellkamp AS, Bax JJ. Analysis 
of ventricular activation using surface electrocardiography to predict left ventricular 
reverse volumetric remodeling during cardiac resynchronization therapy. Circulation 
2010;121:626-34. 
18. 
Gold MR, Birgersdotter-Green U, Singh JP, et al. The relationship between ventricular 
electrical delay and left ventricular remodelling with cardiac resynchronization therapy. 
Eur Heart J 2011;32:2516-24. 
19. 
Lustgarten DL, Calame S, Crespo EM, Calame J, Lobel R, Spector PS. Electrical 
resynchronization induced by direct His-bundle pacing. Heart Rhythm 2010;7:15-21. 
20. 
Deshmukh P, Casavant DA, Romanyshyn M, Anderson K. Permanent, direct His-bundle 
pacing: a novel approach to cardiac pacing in patients with normal His-Purkinje 
activation. Circulation 2000;101:869-77. 
21. 
Barba-Pichardo R, Manovel Sanchez A, Fernandez-Gomez JM, Morina-Vazquez P, 
Venegas-Gamero J, Herrera-Carranza M. Ventricular resynchronization therapy by direct 
His-bundle pacing using an internal cardioverter defibrillator. Europace 2013;15:83-8. 
22. 
Parikshit S.Sharma GD, MD,FHRS, Angela Naperkowski, Jess W.Oren, Randle H.Storm, 
Kenneth A.Ellenbogen, Pugazhendhi Vijayaraman. Permanent His-bundle pacing is 
feasible, safe, and superior to right ventricular pacing in routine clinical practice. Heart 
Rhythm 2014;0:1-8. 
23. 
Lee MY, Yeshwant SC, Lustgarten DL. Honing in on optimal ventricular pacing sites: an 
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Manovel A, Barba-Pichardo R, Tobaruela A. Electrical and mechanical cardiac 
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& circulation 2011;20:769-72. 
25. 
Dabrowski P, Kleinrok A, Kozluk E, Opolski G. Physiologic resynchronization therapy: 
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LBBB during 2 years of observation. Journal of Cardiovascular Electrophysiology 
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Wu G, Cai Y, Huang W, Su L. Hisian pacing restores cardiac function. Journal of 
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Lustgarten DL, Crespo EM, Arkhipova-Jenkins I, et al. His-bundle pacing versus 
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Epstein AE, DiMarco JP, Ellenbogen KA, et al. 2012 ACCF/AHA/HRS focused update 
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Page 16 of 17 
 
Version:  2019Dec09 
15.  APPENDIXES 
 
A. QUESTIONNAIRE 
 
Kansas City Cardiomyopathy Questionnaire 
 
 
 
 
 
KCCQ_2006_no sig 
line.pdf

 
Page 17 of 17 
 
Version:  2019Dec09 
B. SCHEDULE OF EVENTS (SCHEMA) 
 
 
Pre-Implant 
(Screening) 
Implant & 
Periprocedure 
(Day 0) 
Week 2d 
Month 1d 
Month 3 
Month 6 
Month 12 
Year 2 & 
Year 3 
Medical Records 
Review 
X 
 
 
 
 
 
 
X 
Clinical 
Evaluation 
X 
X 
X 
X 
X 
X 
X 
 
Electrocardiogram 
X 
Xc 
 
 
X 
X 
X 
 
Echocardiogram 
X 
 
 
 
 
X 
X 
 
Urine Pregnancy 
Testa 
X 
 
 
 
 
 
 
 
Kansas City 
Cardiomyopathy 
Questionnaire 
X 
 
 
 
 
X 
X 
 
NYHA Functional 
Class 
Determination 
X 
 
 
 
 
X 
X 
 
Randomization 
Xb 
 
 
 
 
 
 
 
Device 
Interrogation 
 
Xc 
X 
X 
X 
X 
X 
 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
 
 
a Only for women of childbearing potential 
b Pre-procedure to facilitate planning of procedure 
c Pre-discharge 
d Week 2 and Month 1 visits may be combined, per treating doctor discretion