Fluoroless Conduction System Implant
Conditions: Pacemaker, Conduction System Pacing
Sponsor: Imperial College London

 
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Fluoroless Conduction System Implant 
 
 
Version 3 06.8.2024 
 
 
 
MAIN SPONSOR: Imperial College Healthcare NHS Trust 
FUNDERS: Johnson and Johnson IIS 
STUDY COORDINATION CENTRE: Dr Akriti Naraen 
IRAS Project ID: 343445 
REC reference:  
 
 
 
Protocol authorised by: 
 
Name & Role 
Date 
Signature 
Prof. Zachary Whinnett 
Investigator 
01.03.24 
Prof. Zachary Whinnett 
 
 
 
 
 
 
 
 
Study Management Group 
 
Chief Investigator: Prof Zachary Whinnett 
 
Co-investigators: Dr Akriti Naraen, Dr Ahran Arnold 
 
Statistician: Prof Darrel Francis 
 
Study Management: Dr Akriti Naraen 
 
 

 
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Study Coordination Centre  
 
For general queries, supply of study documentation, and collection of data, please contact: 
 
Study Coordinator: Dr Akriti Naraen 
Registration: MBCHb, MRCP 
Address: NHLI, B Block, Hammersmith Hospital, Du Cane Road, W12 0HS 
 
 
    
 
Tel: 02033133000  
 
 
 
 
E-mail: anaraen@ic.ac.uk 
Fax:  n/a 
 
 
 
 
 
 
 
 
 
Clinical Queries 
 
Clinical queries should be directed to Dr Akriti Naraen who will direct the query to the appropriate 
person 
 
Sponsor 
 
Imperial College Healthcare NHS Trust is the main research Sponsor for this study.  For further 
information regarding the sponsorship conditions, please contact the Head of Regulatory Compliance 
at: 
 
Level 5 Sherfield building, South Kensington campus 
 
 
 
 
Funder 
 
This study will be funded by the Johnson and Johnson IIS.  
 
This protocol describes the study and provides information about procedures for entering participants.  
Every care was taken in its drafting, but corrections or amendments may be necessary. These will be 
circulated to investigators in the study.  Problems relating to this study should be referred, in the first 
instance, to the Chief Investigator.  
 
This study will adhere to the principles outlined in the UK Policy Frame Work for Health and Social 
Care Research. It will be conducted in compliance with the protocol, the Data Protection Act and other 
regulatory requirements as appropriate.  
 
 
 

 
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Table of Contents 
GLOSSARY OF TERMS ...................................................................................................................................................... 3 
STUDY SUMMARY ........................................................................................................................................................... 5 
1. 
INTRODUCTION ..................................................................................................................................................... 6 
1.1 
BACKGROUND ........................................................................................................................................................... 6 
1.2 
ORIGINAL HYPOTHESIS ................................................................................................................................................ 7 
1.3 
RATIONAL FOR CURRENT STUDY .................................................................................................................................... 7 
2. 
STUDY OBJECTIVES ................................................................................................................................................ 7 
3. 
RECRUITMENT ....................................................................................................................................................... 7 
4. 
METHODOLOGY ..................................................................................................................................................... 8 
4.1 
DERIVATION .............................................................................................................................................................. 8 
4.2 VALIDATION ....................................................................................................................................................................... 9 
4.3 CONTROL ARM ................................................................................................................................................................. 10 
4.4 FOLLOW-UP ..................................................................................................................................................................... 10 
4.5 BURDEN/RISK .................................................................................................................................................................. 10 
4.6 STUDY OUTCOME MEASURES .............................................................................................................................................. 11 
5 
PARTICIPANT ENTRY ............................................................................................................................................ 12 
5.1 
PRE-REGISTRATION EVALUATIONS ................................................................................................................................ 12 
5.2 
INCLUSION CRITERIA ................................................................................................................................................. 12 
5.3 
EXCLUSION CRITERIA ................................................................................................................................................. 12 
5.4 
WITHDRAWAL CRITERIA ............................................................................................................................................. 12 
5.5 
CONSENT ................................................................................................................................................................ 12 
6 
ADVERSE EVENTS ................................................................................................................................................. 13 
6.1 
DEFINITIONS ............................................................................................................................................................ 13 
6.2 
REPORTING PROCEDURES ........................................................................................................................................... 13 
6.3 
NON SERIOUS AES .................................................................................................................................................... 13 
6.4 
SERIOUS AES ........................................................................................................................................................... 13 
7 
ASSESSMENT AND FOLLOW-UP ............................................................................................................................ 14 
8 
STATISTICS AND DATA ANALYSIS ......................................................................................................................... 14 
9 
REGULATORY ISSUES ........................................................................................................................................... 15 
9.1 
ETHICS APPROVAL ..................................................................................................................................................... 15 
9.2 
CONSENT ................................................................................................................................................................ 15 
9.3 
CONFIDENTIALITY ..................................................................................................................................................... 15 
9.4 
INDEMNITY ............................................................................................................................................................. 15 
9.5 
SPONSOR ................................................................................................................................................................ 15 
9.6 
FUNDING ................................................................................................................................................................ 16 
9.7 
AUDITS .................................................................................................................................................................. 16 
10 
STUDY MANAGEMENT ......................................................................................................................................... 16 
11 
PUBLICATION POLICY ........................................................................................................................................... 16 
12 
REFERENCES ........................................................................................................................................................ 17 
 
Glossary of Terms 
 

 
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CSP: Conduction system pacing 
CT: Computed tomography 
ECG: Electrocardiogram 
EGM: Electrogram 
HBP: His-bundle pacing 
ICE: Intracardiac echocardiogram 
LBBB: Left bundle branch block 
LBP: Left bundle pacing 
LBAP: Left bundle area pacing 
LV: Left ventricle 
LVAT: Left ventricular activation time 
MRI: Magnetic resonance imaging 
RV: Right ventricle 
TOE: Transoesophageal echocardiogram 
TTE: Transthoracic echocardiogram 
 
 
 

 
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Study Summary 
 
TITLE 
Fluoroless Conduction System Implant 
DESIGN 
Cohort observational study and interventional at validation phase 
AIMS 
1. Define a feasible fluoroless protocol for conduction system lead implantation 
 
 
OUTCOME 
MEASURES 
Primary Outcomes:  
1. Success rate of conduction system lead implant 
Secondary Outcomes: 
2. Fluoroscopy time 
3. Total procedure time 
4. Capture threshold 
5. Number of times leads deployed 
6. Complication rates: 
a. Lead implanted at the incorrect position: non-septal positions 
b. Lead displacement 
c. Lead injury 
d. Rise in threshold (late complication) 
e. Vascular injury  
f. Perforation with or without subsequent tamponade 
g. Device related infection 
h. Pneumothorax 
 
 
POPULATION 
Patients with any indication for a pacemaker 
ELIGIBILITY 
Main Inclusion Criteria 
1. Patients with a ventricular pacing indication: high grade atrioventricular block and 
symptomatic trifasicular or bifasicular block. (in order to assess the level of 
conduction system block) 
2. Adults willing to take part (ages 18 – 100 years old)   
3. Able to give consent. 
 
Main Exclusion Criteria 
1. Unable to give consent 
2. Children age < 18 years and adults > 100 years old 
3. Pregnant patients 
4. Pacing device in situ 
5. Indication for cardiac resynchronisation therapy 
5.  
DURATION 
 1 year 
 
 
 

 
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1. Introduction 
 
1.1 Background 
 
Discovering how to clinically deliver conduction system pacing efficiently could be a paradigm shift. 
Early work on conduction system pacing focused on the His bundle, with right atrial mapping for the 
His signal and deployment of a lumenless pacing lead(1). Left bundle pacing (LBP) then emerged as 
an alternative, approaching via the basal right ventricular septum to deploy a lead through the septum 
to capture the left bundle on the left side of the septum(2,3) 
 
Current literature report improved left ventricular function, heart failure outcomes and mortality in 
conduction system pacing(4,5). Additionally, LBP has a larger target area, can be done with low 
capture thresholds, has better threshold stability and large amplitude R waves(3). Widespread roll out 
of conduction system pacing clinically, however, faces three major challenges. 
 
Challenge A1: Identifying target area for lead deployment 
Despite growing adoption, conduction system pacing implants remains challenging. Even experienced 
device consultants take time to learn the technique. Experienced centres achieve implant success of 
95%, but centres with new conduction system implanters (but highly experienced pacemaker 
implanters) have rates as low as 56%(6,7). 
 
Fluoroscopic interpretation is challenging, for several reasons. The target area is smaller than 
conventional right ventricular pacing, and can be even smaller when there is fibrosis in the septum. 
The chambers may well be dilated, which displaces not only the fluoroscopic position of the target, but 
also its orientation. The lead can also be difficult to advance, because of septal fibrosis, unrecognised 
lead entanglement and unclear trans-septal trajectory. Interpretation of surface ECG and lead data is 
not straightforward either: there are many levels in the conduction system at which block can occur 
and it is difficult to distinguish them confidently. Lead entanglement and mal-orientation may be 
detectable with elaborate equipment such as intracardiac echocardiography (ICE) but we do not know 
what fluoroscopic or electrical features might provide routine clinical operators with a timely warning. 
Previous approaches to address these issues have involved normal-heart cadaveric studies which do 
not give the electrical context of a clinical implant(8).  
 
These challenges can be overcome with visualising the cardiac anatomy that can be achieved with 
electroanatomical mapping. These 3D mapping systems are also being used to develop fluoroless 
implant strategies. Cumulative radiation exposure is a well-documented operator risk that has been 
minimised through various approaches that include personal lead protection, lead shields, image 
intensifier position, reduced frame rate and short acquisitions (9,10). With the reduction in fluoroscopy 
time in this study, cumulative radiation exposure to implanters is further reduced through a novel 
method.   
 
Advances in electroanatomical mapping have allowed fluoroless techniques to have similar procedure 
times to conventional conduction system implant methods. Fluoroless His-bundle implants have been 
described in small observational studies, using Abbott’s Ensite Precision mapping systems. (11–15) 
 
 
 

 
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1.2 Original Hypothesis 
 
1. Conduction system leads can be implanted with almost no fluoroscopy using electro-
anatomical mapping 
2. Using electro-anatomical mapping will increase safety of conduction system lead implantation 
3. The procedure times with electro-anatomical mapping will be less than that of conventional 
methods using fluoroscopy 
 
1.3 Rational for Current Study 
 
Currently conductions system pacing can have long fluoroscopy times when compared to 
conventional right ventricular pacing. This may be due to difficult cardiac anatomy, altered lead 
trajectory and obstacles such as entanglement, that is not readily visualised with fluoroscopy. As a 
result operators experience additional cumulative fluoroscopy times. Our study will devise a 
standardised implantation protocol using 3D electroanatomical mapping systems to reduce both 
fluoroscopy and procedure times.  
 
2. Study Objectives 
 
Primary Objective 
The primary objective of this study is develop a fluoroless implant protocol of conduction system leads 
using 3D electroanatomical mapping.  
 
Secondary Objective 
The secondary objectives will be  
1. To reduce the overall procedure and fluoroscopy time with utilisation of targeted lead 
deployment.  
2. Improve complication rates  
 
3. Recruitment 
 
A total of 75 patients will be recruited for the study 
 
50 patients with a ventricular pacing indication (high grade atrioventricular block and symptomatic 
trifasicular or bifasicular block) for pacing will be recruited prospectively. The patients will be divided 
into two groups; 25 patients in the derivation cohort and 25 patients in the validation cohort. The 
derivation cohort will undergo a detailed research protocol to determine the optimised work flow and 
this will be applied prospectively to the validation cohort.  
 
The success rates, procedure times, complication rates and fluoroscopy times will be assessed. The 
25 patients undergoing conventional methods of conduction system pacing will be recruited as a 
control arm to compare these outcomes. 
 
In summary, the 75 patients will be grouped as following; 25 patients in the derivation cohort, 25 
patients in the validation cohort and 25 patients in the control arm. 
 
 

 
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4. Methodology 
4.1 Derivation 
The derivation cohort will comprise of 25 prospectively recruited patients. These patients will undergo 
the research protocol. In these patients, we will attempt to implant a permanent conduction system 
pacing lead, in lieu of the RV or LV lead. The lead will be implanted by operators who have implanted 
more than 40 leads to overcome the learning curve.  
 
 
Pre-implant 
Prior to the procedure, patients will undergo a clinically indicated Cardiac MRI. We will use these 
scans to retrospectively assess for the presence of potential mechanisms which could prevent 
successful lead implantation, such as the presence of septal fibrosis and chamber dimensions, so that 
we can assess how these can contribute to challenges at the time of implant. We will also be able to 
review mechanisms for successful implants. This information will be corroborated with data collected 
from the electro-anatomical maps. 
 
The MRI scans will also be used to merge the anatomical information using CartoMerge to reduce 
procedure times by building the anatomical geometry prior to the mapping-catheter collecting this 
information invasively.  
 
During Implant 
The participants will undergo the following procedural steps after written informed consent is gained: 
 
 
1. A left infraclavicular incision and axillary access for the lead will be gain as per standard clinical 
protocol. 
 
2. Access from the femoral vein will be sought where a sheath will be placed in the femoral vein to 
introduce the mapping catheter.  
 
3. Fast anatomical mapping (FAM) of the right atrial and right ventricular anatomy will be made 
where CartoMerge has not already created this anatomy. This will include the right ventricle, the 
tricuspid valve and the right ventricular outflow tract. Activation and voltage maps will be then be 
made of the His-bundle area (including the His cloud), right ventricle, right ventricular outflow 
tract and right ventricular septum.  
 
This will help determine a few key aspects 
1. Level of conduction system block and therefore guide site of lead deployment 
2. Anatomy of the right heart and overcome challenges this may propose 
3. Evidence of septal fibrosis and/or scar that need to be overcome 
4. Activation pattern of the septum in conduction system block 
 
4. Anatomical FAM maps, voltage maps and activation patterns will be compared against the data 
collected from the cardiac MRI to assess 
1. Accuracy of anatomy 
2. Fibrosis and scar patterns 
 
The CartoMerge module will be used to expedite anatomical mapping using the MRI data collected.  
 

 
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5. The mapping catheter will be removed and an intracardiac echo (ICE) catheter, will be inserted 
through the femoral vein. 
 
6. The conduction system pacing lead will be inserted through the axillary vein. A right atrial lead 
will be inserted into the right ventricular apex for back up pacing in the instance the conduction 
system is bumped. The basal-septum, mid-septum, high-septum and anterior walls will be 
paced to identify electrical markers for optimal implant sites. 
 
7. The lead will be visualised on the Carto maps created. 
 
 
8. The lead will be deployed at the predetermined target site under direct visualisation using the 
ICE catheter. Through direct visualisation, three key determinants can be assessed:     
1. Lead trajectory through the septum with the goal of achieving perpendicularity 
2. Lead septum interaction and whether there is evidence of entanglement preventing 
lead progression.  
3. Relationship between the sheath and lead that can lead to or prevent failure of lead 
deployment. 
  
9. Once the conduction lead is secured the right atrial lead will be pulled back and secured in the 
right atrium.  
 
10. The procedure will be completed as per standard clinical implant protocol with routine clinical 
follow-up thereafter:  
 
 
The information from echocardiography will be corroborated with the lead-septum interaction 
visualised on electro-anatomical maps created on CARTO. 
 
In this cohort of patients, the conduction system lead will initially pace the His-bundle then the left 
bundle in order to collect data for both methods of physiological pacing. The information collected 
from ICE and electro-anatomical mapping will be used to develop a streamlined workflow that will 
map targeted areas, where challenging implant sites will be rapidly identified (such as areas of scar), 
reducing the number of attempted lead deployments and visualise lead-septum interaction, apposition 
and progression, improving safety parameters.  
 
At the end of the procedure, the lead position will be documented with a very short, single 
fluoroscopic acquisition. This remains integral for future comparison in the instances of lead 
complications and in particular lead displacement.  
 
 
4.2 Validation 
 
25 patients will be recruited to the validation cohort.  
 
An optimised work flow will be derived using the information collected from the derivation cohort. 
Namely, the target areas for FAM and electro-anatomical maps will be determined, and the successful 
pattern of lead septum interaction on CARTO will be defined.  
 

 
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The streamlined workflow will then be applied to 25 prospective patients. The success rates, 
procedure time, fluoroscopy time, capture threshold, number of attempted lead deployments and 
complication rates will be assessed.  
 
4.3 Control Arm 
The control arm will consist of 25 patients undergoing a conduction system pacemaker using 
conventional pacing methods, with the same pacing indications as the study arm. 
 
 
 
 
Figure 1: Recruitment workflow 
 
4.4 Follow-up 
All 75 patients will have standard clinical follow-up at 6 weeks, 6 months and 1 year. The clinical 
information at these visits will be used to identify complications rates that will include lead 
displacement, rise in capture threshold and lead injury, device related infections.  
 
4.5 Burden/Risk 
The main burdens for the patient include: 
1. The extra time taken to perform the experiments and experimental procedures during their 
scheduled clinical procedure due to the additional diagnostic investigations. The right heart 
electro-anatomical mapping will add 10 minutes. The echocardiography will add an additional 
5 minutes.  
2. The extra access in the groin for the mapping catheter and ICE catheter. 
3. Patients receiving unconventional therapy with conduction system lead implantation 
 
Deleted: 

 
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The burden will be mitigated by the minimum extra time being used to complete the experiments, the 
use of local anaesthetic and the immediate removal of extra research related sheaths as soon as they 
are not needed 
 
The main risks for the patient are:  
A conduction system pacing wire is not known to have a higher complication rate compared to a 
conventional pacing wire. Conduction system pacing wires have been shown to be as effective as 
conventional pacing wires at preventing slow heart rates and improving heart pumping. If a 
complication occurs and the conduction system pacing wire cannot be implanted or does not perform 
as expected during follow-up a procedure will be performed to convert your pacing system to a 
conventional pacing system. 
 
The additional risks of vascular tube placement include:  
• 
1% risk of bruising around the area 
• 
1 in 1000 risk of damage to the blood vessels requiring surgery 
• 
Less than 1 in 500 risk of stroke 
The additional risks of intracardiac echocardiogram include 
• 
1% risk of bruising around the access area in the leg 
• 
Less than 1 in 1000 risk of heart perforation 
The additional risks of electro-anatomical mapping include 
• 
Less than 1 in 1000 risk of heart perforation 
 
Therefore, the overall risk of serious complications arising from taking part in the research study are 
less than 4 in 1000 (0.4%) 
 
Pacemaker implantation involves exposure to ionising radiation to visualise lead implantation. Taking 
part in this study involves exposure to additional exposure to radiation above the standard clinical 
procedure due to the additional measurements that will be taken. 
 
Ionising radiation can cause cell damage that may, after many years or decades, turn cancerous. We 
are all at risk of developing cancer during our lifetime. The normal risk is that this will happen to about 
50% of people at some point in their life. Taking part in this study will increase the chances of this 
happening to you from 0.01% to 0.1% (13Gy.cm² (2.1mSv) per patient per procedure). 
 
4.6 Study Outcome Measures 
Primary Outcome Measures 
1. Success rates of conduction system lead implant (fluoroless workflow vs conventional methods) 
 
Secondary Outcome Measures 
 
1. Procedure and fluoroscopy times of the fluoroless workflow vs current conventional methods of 
His-bundle and Left-bundle pacing 
2. Procedure and fluoroscopy times of the fluoroless workflow vs conduction system implant to 
current right ventricular pacing 
3. Assess capture threshold of His-bundle and Left-bundle pacing from the fluoroless workflow vs 
that of conventional methods of conduction system implantation  
4. Number of times leads deployed in the fluoroless protocol vs conventional methods of 
conduction system implantation 
5. Complication rates in the fluoroless protocol vs conventional methods of conduction system 
implantation: 

 
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a. Lead implanted at the incorrect position: non-septal positions 
b. Lead displacement 
c. Lead injury 
d. Rise in threshold (late complication) 
e. Vascular injury  
f. Perforation with or without subsequent tamponade 
g. Device related infection 
h. Pneumothorax 
 
5 Participant Entry  
5.1 Pre-registration Evaluations 
5.2 Inclusion Criteria 
 
1. Patients with a ventricular pacing indication: high grade atrioventricular block and 
symptomatic trifasicular, bifasicular block or left bundle branch block LBBB for cardiac 
resynchronisation therapy 
2. Adults willing to take part (ages 18 – 100 years old)   
3. Able to give consent. 
 
5.3 Exclusion Criteria 
 
1. Unable to give consent 
2. Children age < 18 years and adults > 100 years old 
3. Pregnant patients 
• 
As per standard of care, female patients of child-bearing age will have a urine pregnancy 
test prior to their procedure.   
 
5.4 Withdrawal criteria 
 
The research protocol will be terminated early if  
1. Patients lose their capacity to consent or become clinically unstable  
2. The patient chooses to withdraw from the study 
3. The sponsor, the chief investigator or the research team review the data and decide to stop 
the study 
 
5.5 Consent 
 
Patients will be identified by members of their direct care team when they attend clinic appointments 
or are admitted as an inpatient to the hospital. Patient records may be reviewed to assess suitability 
and this will be performed by members of the direct care team. Participation in the study will be 
discussed with the patients by their direct care team and information will only be passed on to the 
research team with the patients consent. Verbal consent will be gained by the direct care team for 
personal contact information to be shared with the research team. This will be documented in the 
patient notes. 
 
The direct care team will make patients aware that participation is voluntary and that if they do not 
wish to participate it will not affect their usual care.  

 
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Consent for the study of the prospectively recruited patients will be obtained by a member of the 
research team, this will be a physician who is experienced in performing conduction system 
implantation. Patients will have details of the study discussed with them and any family members or 
friends the patients wish to be present. They will also be provided with written information (patient 
information sheets). Patients will be given as much time as they wish, with a minimum of at least 24 
hours, to decide whether they wish to participate in the study and will be offered additional visits to 
further discuss the study if they wish. Patients are able to withdraw their consent from the study at any 
time. Patients will be made aware that their participation is voluntary and that if they do not want to 
take part it will not affect their usual care. Patients who agree to take part in the study will sign a 
consent form, a copy of the form will be given to the patients and a second copy will be kept in their 
study record file. A copy will also be kept in the site file.  
6 Adverse events 
6.1 Definitions  
 
Adverse Event (AE): any untoward medical occurrence in a patient or clinical study subject.   
 
Serious Adverse Event (SAE): any untoward and unexpected medical occurrence or effect that: 
• 
Results in death 
• 
Is life-threatening – refers to an event in which the subject was at risk of death at the time 
of the event; it does not refer to an event which hypothetically might have caused death if 
it were more severe 
• 
Requires hospitalisation, or prolongation of existing inpatients’ hospitalisation 
• 
Results in persistent or significant disability or incapacity 
• 
Is a congenital anomaly or birth defect 
 
Medical judgement should be exercised in deciding whether an AE is serious in other situations.  
Important AEs that are not immediately life-threatening or do not result in death or hospitalisation but 
may jeopardise the subject or may require intervention to prevent one of the other outcomes listed in 
the definition above, should also be considered serious. 
 
6.2 Reporting Procedures 
 
All adverse events should be reported.  Depending on the nature of the event the reporting procedures 
below should be followed.  Any questions concerning adverse event reporting should be directed to the 
Chief Investigator in the first instance.   
 
6.3 Non serious AEs 
 
All such events, whether expected or not, should be recorded.   
 
6.4 Serious AEs 
 
An SAE form should be completed and faxed to the Chief Investigator within 24 hours.  However, 
hospitalisations for elective treatment of a pre-existing condition do not need reporting as SAEs. 
 
All SAEs should be reported to the “name of REC when allocated” where in the opinion of the Chief 
Investigator, the event was: 
• 
‘related’, ie resulted from the administration of any of the research procedures; and 

 
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• 
‘unexpected’, ie an event that is not listed in the protocol as an expected occurrence 
 
Reports of related and unexpected SAEs should be submitted within 15 days of the Chief Investigator 
becoming aware of the event, using the NRES SAE form for non-IMP studies.  The Chief Investigator 
must also notify the Sponsor of all related and unexpected SAEs. 
 
Local investigators should report any SAEs as required by their Local Research Ethics Committee, 
Sponsor and/or Research & Development Office.  
 
 
Contact details for reporting SAEs 
RGIT@imperial.ac.uk 
Prof. Zachary Whinnett email: z.whinnett@imperial.ac.uk 
Please send SAE forms to: Hammersmith Hospital, Du Cane road, London W12 0HS. 
Tel: 020 8383 4967 (Mon to Fri 09.00 – 17.00) 
7 Assessment and Follow-up 
 
Patients will be followed up for a 1 year period. During this time they will undergo the device 
interrogation and wound check at 6 weeks as part of standard clinical care. One year after device 
implantation, patients will undergo a device interrogation follow-up appointment. Any incidental 
findings that we identify during the study will be reviewed by the research team and reported to the 
GP and also the cardiology team normally looking after the patient.  
 
 
Definition of end of Study 
The end of the study will be defined as completion of the 1 year follow-up of the 75 prospectively 
recruited patients for the invasive aspect of the study. This will be the date of the final visit of the last 
participant at 1 year.  
8 Statistics and data analysis 
 
The following statistical analysis has been reviewed and approved by our statistician, Prof. Darrel 
Francis. 
 
Power Calculations: 
25 patients would provide the ability to determine the mean time of lead implantation of 120 minutes 
with a precision of (as a standard error) approximately ± 10 minutes (assuming standard deviation of 
47min)7 
 
25 patients will provide the ability to determine the percentage of a successful implant with a precision 
of a SE (± 8%) of a success rate of approximately 80% 
SD of implant time = SD of total procedure time / √2 = 67 / √2 =47.37 
SE = SD/ √sample size = 47.37/√25 = 9.47 
 

 
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Data and all appropriate documentation will be stored for a minimum of 5 years after the completion 
of the study, including the follow-up period.   
 
To assess the primary outcome of the success rates of the conduction system lead implant using the 
fluoroless workflow developed during our study, ECG information will be collected and capture will 
be determined by experts.  
 
Fluoroscopy and procedural times will be analysed with one-way ANOVA. Success rates, capture 
thresholds and battery life will be analysed with t-test. 
 
9 Regulatory issues 
 
9.1 Ethics approval 
 
The Study Coordination Centre has obtained approval from the “Name of REC when allocated” and 
Health Research Authority (HRA). The study must also receive confirmation of capacity and capability 
from each participating NHS Trust before accepting participants into the study or any research activity 
is carried out. The study will be conducted in accordance with the recommendations for physicians 
involved in research on human subjects adopted by the 18th World Medical Assembly, Helsinki 1964 
and later revisions. 
 
9.2 Consent  
 
Consent to enter the study must be sought from each participant only after a full explanation has been 
given, an information leaflet offered and time allowed for consideration.  Signed participant consent 
should be obtained.  The right of the participant to refuse to participate without giving reasons must be 
respected.  After the participant has entered the study the clinician remains free to give alternative 
treatment to that specified in the protocol at any stage if he/she feels it is in the participant’s best interest, 
but the reasons for doing so should be recorded.  In these cases the participants remain within the 
study for the purposes of follow-up and data analysis.  All participants are free to withdraw at any time 
from the protocol treatment without giving reasons and without prejudicing further treatment. 
 
9.3 Confidentiality 
 
The Chief Investigator will preserve the confidentiality of participants taking part in the study and is 
registered under the Data Protection Act.  
Data will be pseudonymised. 
 
9.4 Indemnity 
 
Imperial College Healthcare NHS Trust holds standard NHS Hospital Indemnity and insurance cover 
with NHS Resolution for NHS Trusts in England, which apply to this study  
9.5 Sponsor 
 

 
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Imperial College Healthcare NHS Trust will act as the main Sponsor for this study.  Delegated 
responsibilities will be assigned to the NHS trusts taking part in this study.   
 
9.6 Funding 
 
Johnson and Johnson 
 
Patients' transport in the form of a taxi will be provided as well as refreshments during the additional 
appointments for purposes of the research study. We have costed £50 for transport and £10 for 
refreshments per visit. 
 
Researchers will not receive any personal payment over and above normal salary, or any other 
benefits or incentives, for taking part in this research. 
 
9.7 Audits  
 
The study may be subject to inspection and audit by Imperial College Healthcare NHS Trust under 
their remit as sponsor and other regulatory bodies to ensure adherence to GCP and the UK Policy 
Frame Work for Health and Social Care Research 
10 Study Management 
 
The day-to-day management of the study will be co-ordinated by Dr Akriti Naraen. 
11 Publication Policy 
 
Our aim to publish in a major international cardiology journal and present at international cardiology 
conferences. Findings will also be published in internal reports and presented in local meetings. 
 
 
 

 
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12 References 
 
1. 
Arnold AD, Whinnett ZI, Vijayaraman P. His-Purkinje conduction system pacing: State of the art 
in 2020. Arrhythm Electrophysiol Rev. 2020;9(3).  
2. 
Arnold AD, Shun-Shin MJ, Keene D, Howard JP, Chow JJ, Lim E, et al. Electrocardiographic 
predictors of successful resynchronization of left bundle branch block by His bundle pacing. J 
Cardiovasc Electrophysiol. 2021;32(2).  
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