Characterising the Stable and Dynamic Left Atrial Substrate in Atrial Fibrillation Using High Density Contact and Non-contact Mapping
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: Oxford University Hospitals NHS Trust

Study Protocol and Statistical Analysis Plan: Characterising the 
Stable and Dynamic Left Atrial Substrate in Atrial Fibrillation 
 
NCT04229472 
 
9th March 2023 
 

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Study Title: Characterising the stable and dynamic left atrial substrate in atrial fibrillation using high 
density contact and non-contact mapping 
Internal Reference Number / Short title: CASDAF-HD 
Ethics Ref: 20/LO/0150 
Date and Version No: 9thth March 2023, Version 3.0 
 
Chief Investigator: 
Dr Timothy R Betts 
Department of Cardiology, John Radcliffe Hospital, Headley Way, 
Oxford, OX3 9DU 
Investigators:  
Dr Alexander J Sharp 
Department of Cardiology, John Radcliffe Hospital, Headley Way, 
Oxford, OX3 9DU 
Dr Michael TB Pope 
Department of Cardiology, John Radcliffe Hospital, Headley Way, 
Oxford, OX3 9DU 
Dr Rohan Wijesurendra 
Oxford Cardiac Magnetic Resonance Centre 
Sponsor:  
Oxford University Hospitals NHS Foundation Trust 
Funder: 
Oxfordshire Health Services Research Committee, part of Oxford 
Hospitals Charity 
CRM Hub account 
Chief Investigator Signature:   
 
There are no conflicts of interest 
 
 
Confidentiality Statement 
This document contains confidential information that must not be disclosed to anyone other than the 
Sponsor, the Investigator Team, HRA, host organisation, and members of the Research Ethics Committee, 
unless authorised to do so. 
 

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TABLE OF CONTENTS 
 
1. 
SYNOPSIS ................................................................................................................................................ 5 
2. 
ABBREVIATIONS ..................................................................................................................................... 6 
3. 
BACKGROUND AND RATIONALE ............................................................................................................ 7 
4. 
OBJECTIVES AND OUTCOME MEASURES ............................................................................................... 8 
5. 
STUDY DESIGN ...................................................................................................................................... 10 
6. 
PARTICIPANT IDENTIFICATION ............................................................................................................. 10 
6.1. 
Study Participants ......................................................................................................................... 10 
6.2. 
Inclusion Criteria ........................................................................................................................... 10 
6.3. 
Exclusion Criteria ........................................................................................................................... 11 
7. 
STUDY PROCEDURES ............................................................................................................................ 11 
7.1. 
Recruitment .................................................................................................................................. 11 
7.2. 
Screening and Eligibility Assessment ............................................................................................ 12 
7.3. 
Informed Consent ......................................................................................................................... 12 
7.4. 
Baseline Assessments ................................................................................................................... 12 
7.5. 
Pre-procedure cardiac MRI ........................................................................................................... 13 
7.6. 
Study visit (control group)............................................................................................................. 13 
7.7. 
Study visit (excluding control group) ............................................................................................ 13 
7.8. 
Follow up ....................................................................................................................................... 14 
7.9. 
Discontinuation/Withdrawal of Participants from Study ............................................................. 15 
7.10. 
Definition of End of Study ........................................................................................................... 15 
8. 
SAFETY REPORTING .............................................................................................................................. 15 
8.1. 
Definition of Serious Adverse Events ............................................................................................ 15 
8.2. 
Reporting Procedures for Serious Adverse Events ....................................................................... 16 
9. 
STATISTICS AND ANALYSIS ................................................................................................................... 16 
9.1. 
Description of Statistical Methods ................................................................................................ 16 
9.2. 
The Number of Participants .......................................................................................................... 16 
9.3. 
Analysis of Outcome Measures..................................................................................................... 17 
10. 
DATA MANAGEMENT......................................................................................................................... 18 
10.1. 
Access to Data ............................................................................................................................. 18 
10.2. 
Data Recording and Record Keeping .......................................................................................... 18 
11. 
QUALITY ASSURANCE PROCEDURES .................................................................................................. 18 
12. 
ETHICAL AND REGULATORY CONSIDERATIONS ................................................................................. 18 

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12.1. 
Declaration of Helsinki ................................................................................................................ 18 
12.2. 
Guidelines for Good Clinical Practice .......................................................................................... 18 
12.3. 
Approvals .................................................................................................................................... 19 
12.4. 
Reporting .................................................................................................................................... 19 
12.5. 
Participant Confidentiality .......................................................................................................... 19 
12.1. 
Expenses and Benefits ................................................................................................................ 19 
12.2. 
Cardiac MRI ................................................................................................................................. 19 
13. 
FINANCE AND INSURANCE ................................................................................................................. 20 
13.1. 
Funding ....................................................................................................................................... 20 
13.2. 
Insurance .................................................................................................................................... 20 
14. 
PUBLICATION POLICY ......................................................................................................................... 21 
15. 
REFERENCES ....................................................................................................................................... 21 
16. 
APPENDIX A:  PARTICIPANT GROUP ALLOCATION AND STUDY FLOW CHART .................................. 23 
17. 
APPENDIX B: Table distinguishing routine and study procedures and estimated additional time 
requirements ............................................................................................................................................... 25 
18. 
APPENDIX B:  SCHEDULE OF STUDY PROCEDURES ............................................................................ 26 
19. 
APPENDIX C:  AMENDMENT HISTORY................................................................................................ 27 
 
 
 

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1. SYNOPSIS 
Study Title 
Characterising the stable and dynamic left atrial substrate in atrial 
fibrillation using high density contact and non-contact mapping 
Internal ref. no. / short 
title 
CASDAF-HD 
Study Design 
Prospective non-randomised mechanistic investigation 
Study Participants 
Adults aged ≥18 with atrial fibrillation undergoing catheter ablation and 5 
controls undergoing ablation of left sided accessory pathways 
Planned Sample Size 
35 (30 patients with AF and 5 supraventricular tachycardia (SVT)) 
Planned Study Period 
2 years 
 
Objectives 
Outcome Measures 
Primary 
 
To define the normal range of voltage 
amplitude identified using the Abbott 
EnSite Advisor HD grid (SE) catheter 
and HD wave solution and response to 
pacing cycle lengths using a control 
group with normal left atria 
Mean and distribution of left atrial 
voltage amplitude across the 
whole chamber and by segments 
with lower limit of normal defined 
as the upper 95% value within the 
segment with the lowest mean 
amplitude at long pacing cycle 
length 
Secondary 
 
To characterise the left atrial 
electrophysiological substrate using 
electroanatomical voltage and 
activation mapping using the Abbott 
EnSite Advisor HD grid (SE) catheter 
during pacing using a basic cycle 
length and a single closely coupled 
extra-stimulus in a cohort of patients 
undergoing catheter ablation for atrial 
fibrillation. 
A change in electrogram 
morphology from normal to 
abnormal (defined as ≥3 
deflections lasting ≥50ms) 
between long and short pacing 
cycle length in regions of low 
(<0.5mV), intermediate (0.5-lower 
limit of normal defined from 
control group) and normal 
(defined from control group 
results) voltage amplitude. 
 
 
Difference in single vector 
conduction velocity at long and 
short cycle lengths in regions of 
low, intermediate and normal 
voltage. 
 
In a subgroup of 20 patients: 
To compare electroanatomic voltage 
mapping (EAVM) performed with a 
bipolar contact force guided ablation 
catheter to the Abbott HD grid using 
orthogonal wave analysis in sinus 
rhythm. 
1. Difference in voltage amplitude 
by each method in sinus rhythm 
2. Surface area and proportion of 
points of scar (<0.05mV), low 
voltage (0.05-0.4mV), intermediate 
voltage and normal voltage 
(voltage cut-offs defined from 
control group). 
 
In a subgroup of 10 patients: 
Correlate findings of high density 
Correlate electrogram amplitude 
and morphology with regions of 

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contact mapping with AF propagation 
patterns using the AcQMap combined 
imaging and electrophysiological 
mapping system. 
uniform, irregular, slow or 
rotational activation patterns 
during AF. 
 
To evaluate the distribution of late 
gadolinium enhancement on cardiac 
MRI relative to conduction properties 
identified using the HD grid (as above)  
Electrogram 
amplitude, 
morphology 
and 
conduction 
velocities at long and short cycle 
length in regions with and without 
late gadolinium enhancement on 
cardiac MRI 
 
Correlate dynamic propagation 
patterns with distribution of atrial scar 
derived from cardiac MRI 
Difference in distribution of late 
gadolinium enhancement in 
regions of predominant rotational 
and irregular activation during AF.  
 
Evaluate the effect of ablation on left 
atrial scar derived from cardiac MRI 
Difference in burden of late 
gadolinium enhancement on pre-
and post procedure cardiac MRI. 
 
In 5 control patients: 
Evaluate the effect of cycle length on 
electrogram morphology in normal 
subjects 
A change in electrogram 
morphology from normal to 
abnormal (defined as ≥3 
deflections lasting ≥50ms), 
amplitude and duration between 
long and short pacing cycle length 
 
2. ABBREVIATIONS 
AF 
Atrial fibrillation 
CI 
Chief Investigator 
CRF 
Case Report Form 
EAVM 
Electroanatomic Voltage Mapping 
GCP 
Good Clinical Practice 
GP 
General Practitioner 
HRA 
Health Research Authority 
ICF 
Informed Consent Form 
LGE-MRI 
Late Gadolinium Enhanced – Magnetic Resonance Imaging 
NHS 
National Health Service 
NRES 
National Research Ethics Service 
PI 
Principal Investigator 
PIL 
Participant/ Patient Information Leaflet 
R&D 
NHS Trust R&D Department 
REC 
Research Ethics Committee 
SOP 
Standard Operating Procedure 

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3. BACKGROUND AND RATIONALE 
Atrial fibrillation is a common condition resulting in significant morbidity and mortality. Catheter 
ablation based around a strategy of pulmonary vein isolation is increasingly used to maintain sinus 
rhythm.(1) However, particularly in patients with persistent atrial fibrillation, efficacy is limited with 
single-procedure success rates of <50%.(2-5) Although a number of techniques targeting non-pulmonary 
vein mechanisms have been explored, none has demonstrated superior efficacy in randomised 
controlled trials.(5) This is in large part due to a lack of understanding of AF mechanisms or subgroups of 
AF phenotypes and the contribution of identified conduction patterns to arrhythmia maintenance and 
propagation.  
Assessment of atrial substrate is often performed through electroanatomical voltage mapping 
(EAVM) using multipolar or bipolar catheters. Regions of low voltage amplitude, used as a surrogate for 
fibrosis, predict worse outcomes following catheter ablation.(6-8) Prior studies have varied in the 
technology used to conduct EAVM and how low voltage areas are defined. They have largely focused on 
regions with bipolar amplitude <0.5mV with normal being defined as >1.1 or 1.3mV.(9, 10) The 
significance of regions with amplitude between these values (intermediate voltage) is poorly understood 
but there is some evidence that highly fractionated electrograms are seen in these areas(9, 10) which 
correlate with patchy enhancement rather than dense fibrosis on late gadolinium enhanced cardiac MRI 
(LGE-MRI). The presence of intermediate and low voltage areas is associated with AF recurrence 
following pulmonary vein isolation (PVI).(11, 12) Interestingly, a significant proportion of patients 
undergoing catheter ablation for persistent AF do not demonstrate regions of low voltage implying that 
it is not purely these regions that are important for AF maintenance.(7, 13) There also appears to be 
fairly poor correlation between AF duration and the presence of fibrosis, with some patients with 
longstanding AF demonstrating scar-free atria, whilst some with only brief episodes have highly scarred 
atria.(13, 14)  
EAVM may significantly underestimate fibrosis when compared with MRI. One MRI study found  
>20% atrial fibrosis in 51% of patients and a second study found >10% fibrosis in 81%.(14, 15) Rolf’s 
study assessing ablation of low voltage areas found these to be present in only 26% of patients.(7) This 
suggests that current strategies of EAVM fail to detect a significant proportion of fibrosis seen in MRI. 
This may be the result of regions of patchy fibrosis with relatively preserved voltage amplitude but 
abnormal conduction properties, important for AF propagation. 
Studies have shown an increase in total atrial conduction time with increasing duration of AF and a 
corresponding slowing in conduction velocity.(10) Conduction velocities are significantly reduced in low 
voltage areas (<0.5mV) but are less thoroughly studied in regions of intermediate voltage.(16) 
Furthermore, the majority of this work has been undertaken in sinus rhythm. Conduction velocity and 
refractoriness are significantly affected by the interval between successive beats.  Ectopic (premature) 
beats, usually originating in the pulmonary veins, commonly trigger AF. Therefore, although resting atrial 
conduction properties (and electrogram morphology) may appear normal, response to closely coupled 
ectopic activation could be impaired and contribute to the initiation and maintenance of fibrillation. 
EAVM during AF is influenced by the effect of wavefront directionality on bipolar electrogram 
amplitude. The novel Abbott EnSite Advisor HD grid (SE) catheter uses orthogonal bipoles to reduce the 

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effect of wavefront direction (HD wave solution) and is therefore designed to facilitate more accurate 
substrate assessment compared to conventional bipolar mapping catheters. Appropriate voltage 
amplitude values representing the cut-off between normal and abnormal will vary with the catheter 
used (the result of electrode size and spacing) and has not been clearly defined with this technology.  
The HD grid catheter is still a traditional “point by point” mapping system whereby small areas of the 
atrium are examined in sequence. Non-contact dipole density mapping facilitated by the AcQMap system 
from Acutus Medical allows real-time visualisation of whole chamber activation during AF and reveals 
complex propagation patterns. These patterns are highly variable between patients and their detailed 
analysis may identify important patterns related to the underlying electrophysiological substrate that 
may further our understanding of AF mechanisms and help guide effective ablation strategies. 
This study therefore aims to conduct detailed EAVM using the Abbott HD grid catheter in 5 control 
patients undergoing ablation of left sided accessory pathways who are thought to have normal atria in 
order to define normal voltage amplitude and the response to changing activation rate. Detailed EAVM 
will then be performed in patients undergoing catheter ablation for AF in order to evaluate atrial 
properties at both long and short pacing cycle lengths. In 2 separate subgroups, the orthogonal HD grid 
mapping will be compared to either AcQMap propagation patterns or to a conventional bipolar ablation 
catheter with contact force. It is hypothesised that regions of intermediate voltage will demonstrate 
exaggerated slowing in conduction velocity and broadening of electrograms with shortening cycle length 
compared to regions of preserved amplitude, which will correlate with regions of slow and irregular 
propagation patterns during atrial fibrillation and late gadolinium enhancement on cardiac MRI. 
Furthermore, EAVM using the HD grid catheter will reveal higher mean electrogram amplitude compared 
to bipolar mapping with a lower surface area identified as low voltage (<0.5mV). The improved mapping 
resolution provided by the HD wave solution and HD grid catheter alongside use of varying activation 
times will facilitate greater understanding of the variable and patient specific AF substrate involved in AF 
maintenance. It is anticipated that combining this with non-invasive assessment of fibrosis distribution 
through cardiac MRI and AF propagation patterns visualised by panoramic mapping will provide pilot 
data with the potential to identify sub-groups of AF phenotypes. This data can then be applied to larger 
multi-centre studies of substrate mapping to better characterise the arrhythmic substrate and develop 
patient specific ablation strategies. 
4. OBJECTIVES AND OUTCOME MEASURES 
Objectives 
Outcome Measures  
Timepoint(s) 
of 
evaluation of this 
outcome measure 
(if applicable) 
Primary 
To define the normal range of 
voltage amplitude identified using 
the Abbott EnSite Advisor HD grid 
(SE) catheter and HD wave solution 
and response to pacing cycle lengths 
using a control group with normal 
Mean and distribution of left atrial voltage 
amplitude across the whole chamber and 
by segments with lower limit of normal 
defined as the upper 95% value within the 
segment with the lowest mean amplitude 
at long pacing cycle length 
During 
ablation 
procedure 

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left atria 
Secondary: 
To characterise the left atrial 
electrophysiological substrate using 
electroanatomical voltage and 
activation mapping using the Abbott 
EnSite Advisor HD grid (SE) catheter 
during pacing using a basic cycle 
length and a single closely coupled 
extra-stimulus in a cohort of patients 
undergoing catheter ablation for 
atrial fibrillation. 
A change in electrogram morphology from 
normal to abnormal (defined as ≥3 
deflections lasting ≥50ms) between long 
and short pacing cycle length in regions of 
low (<0.5mV), intermediate (0.5-lower 
limit of normal defined from control 
group) and normal (defined from control 
group results) voltage amplitude. 
During 
ablation 
procedure 
 
Difference in single vector conduction 
velocity at long and short cycle lengths in 
regions of low, intermediate and normal 
voltage. 
During 
ablation 
procedure 
In a subgroup of 20 patients: 
To compare electroanatomic voltage 
mapping (EAVM) performed with a 
bipolar contact force guided ablation 
catheter to the Abbott HD grid using 
orthogonal wave analysis in sinus 
rhythm. 
1. Difference in voltage amplitude by each 
method in sinus rhythm 
2. Surface area and proportion of points of 
scar (<0.05mV), low voltage (0.05-0.4mV), 
intermediate voltage and normal voltage 
(voltage cut-offs defined from control 
group). 
During 
ablation 
procedure 
In a subgroup of 10 patients: 
Correlate findings of high density 
contact mapping with AF 
propagation patterns using the 
AcQMap combined imaging and 
electrophysiological mapping 
system. 
Correlate 
electrogram 
amplitude 
and 
morphology with regions of uniform, 
irregular, slow or rotational activation 
patterns during AF. 
During 
ablation 
procedure 
To evaluate the distribution of late 
gadolinium enhancement on cardiac 
MRI relative to conduction 
properties identified using the HD 
grid (as above)  
Electrogram amplitude, morphology and 
conduction velocities at long and short 
cycle length in regions with and without 
late gadolinium enhancement on cardiac 
MRI 
During 
ablation 
procedure 
Correlate dynamic propagation 
patterns with distribution of atrial 
scar derived from cardiac MRI 
Difference 
in 
distribution 
of 
late 
gadolinium enhancement in regions of 
predominant 
rotational 
and 
irregular 
activation during AF 
N/A 

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Evaluate the effect of ablation on 
left atrial scar derived from cardiac 
MRI 
Difference in burden of late gadolinium 
enhancement on pre-and post procedure 
cardiac MRI. 
3-6 months post 
procedure 
In 5 control patients: 
Evaluate the effect of cycle length on 
electrogram morphology in normal 
subjects 
A change in electrogram morphology from 
normal to abnormal (defined as ≥3 
deflections lasting ≥50ms), amplitude and 
duration between long and short pacing 
cycle length 
During 
ablation 
procedure 
 
5. STUDY DESIGN 
This is a prospective non-randomised mechanistic study of 35 patients including a control group of 5 
patients with SVT and 30 patients undergoing elective AF ablation. 
The 30 patients undergoing AF ablation will include 10 who are undergoing elective AcQMap guided 
procedures in order to correlate non-contact propagation patterns with contact substrate mapping. 
These 10 patients will also undergo cardiac MRI before and after the ablation procedure.  
The remaining 20 patients will also undergo electroanatomical voltage mapping using a contact force 
guided bipolar ablation catheter in order to compare the two methods/technologies. This is a non-
blinded comparison study. 
The 5 control patients will be undergoing elective catheter ablation procedures for left sided accessory 
pathways. Additional left atrial electroanatomical mapping will be performed to define normal 
electrophysiological properties for comparison. 
Participants will be identified in clinic or after listing for the procedure. Screening and formal recruitment 
will then be undertaken, with the research study conducted during the ablation procedure. No follow up 
is required but participants undergoing AcQmap guided ablation and cardiac MRI will undergo a repeat 
cardiac MRI within 6 months following the procedure. 
6. PARTICIPANT IDENTIFICATION 
6.1. Study Participants 
Patients with atrial fibrillation undergoing an elective catheter ablation procedure and 5 patients 
undergoing elective left sided catheter ablation involving a trans-septal puncture. 
6.2. Inclusion Criteria 
• 
Participant is willing and able to give informed consent for participation in the study. 
• 
Male or Female, aged 18 years or above. 
• 
Diagnosed with paroxysmal or persistent atrial fibrillation and planned for a catheter ablation 
procedure (AF ablation group only). 

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• 
Undergoing elective left sided catheter ablation procedure involving a trans-septal approach. 
(control group only) 
• 
In the Investigator’s opinion is able and willing to comply with all trial requirements. 
6.3. Exclusion Criteria 
• 
Previous cardiac surgery 
• 
Medical history including any of: atrial fibrillation, atrial flutter, hypertension, diabetes mellitus, 
chronic obstructive pulmonary disease, significant mitral valve disease (stenosis or 
regurgitation), pulmonary hypertension, obstructive sleep apnoea, ischaemic heart disease, 
cerebrovascular disease, peripheral vascular disease, structural heart disease (excluding known 
accessory pathway), congenital cardiac anomaly (excluding accessory pathway), previous left 
atrial ablation (catheter or surgical), cardiac surgery (control group only) 
• 
Contradictions to MR scanning (such as metallic or electronic objects implanted in your body or 
history of severe claustrophobia) (AcQMap guided ablation group) 
• 
Significantly impaired renal function (eGFR<30ml/min) 
• 
Female participant who is pregnant, lactating or planning pregnancy during the course of the 
trial. 
• 
Any other significant disease or disorder which, in the opinion of the Investigator, may either put 
the participants at risk because of participation in the trial, or may influence the result of the 
trial, or the participant’s ability to participate in the trial. 
• 
Participants who have participated in another research trial involving an investigational 
medicinal product in the past 12 weeks. (Involvement in any other research trial is not a 
contraindication per se.) 
7. STUDY PROCEDURES 
7.1. Recruitment 
Potential study participants will be identified by medical staff in the outpatient clinic at the time of listing 
for catheter ablation, or by review of patients electronically listed for this procedure. If patients are in 
the clinic and give consent then a member of the research team may approach them at this stage. Some 
members of the clinical team are also part of the research team and therefore if identified by medical 
staff through listing for the procedure, they will be approached by telephone. An information leaflet will 
then be provided by post or email if this has not been provided in clinic with contact details for the 
research team. If willing to participate then formal screening and recruitment will follow. For most, this 
will take place at the time of attendance for standard pre-procedure assessment appointments or when 
attending for the elective procedure. Participants undergoing elective AcQMap guided procedures and 

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requiring cardiac MRI, formal recruitment and consent will take place prior to the initial study MRI scan. 
Information must have been provided with sufficient time for the potential participant to fully consider 
involvement prior to formal recruitment and consent (generally expected to be at least 24 hours).  
7.2. Screening and Eligibility Assessment 
As there is no randomisation, there is no time limit between screening and formal recruitment. It is 
anticipated that these will occur at the same visit to coincide with standard clinical care and avoid an 
extra patient journey. Screening procedures include a review of medical history and demographics and 
recording of height and weight. 
7.3. Informed Consent 
The participant must personally sign and date the latest approved version of the Informed Consent form 
before any trial specific procedures are performed. It is anticipated that this is done at the initial visit, 
which will serve as both the screening and baseline study visit. 
Written and verbal versions of the Participant Information and Informed Consent will be presented to 
the participants detailing no less than: the exact nature of the trial; what it will involve for the 
participant; the implications and constraints of the protocol; the known side effects and any risks 
involved in taking part. It will be clearly stated that the participant is free to withdraw from the trial at 
any time for any reason without prejudice to future care, without affecting their legal rights and with no 
obligation to give the reason for withdrawal. 
The participant will be allowed as much time as wished to consider the information, and the opportunity 
to question the Investigator, their GP or other independent parties to decide whether they will 
participate in the trial. Written Informed Consent will then be obtained by means of participant dated 
signature and dated signature of the person who presented and obtained the Informed Consent. The 
person who obtained the consent must be suitably qualified and experienced, and have been authorised 
to do so by the Chief/Principal Investigator. A copy of the signed Informed Consent will be given to the 
participant and a copy placed in the medical records. The original signed form will be retained at the trial 
site. 
7.4. Baseline Assessments 
Baseline assessments include medical history; current medications and any recently stopped medications 
(with particular reference to anti-arrhythmic drugs and anticoagulants), smoking history, alcohol use, 
and illicit drugs use. Measurements taken should include height, weight and body mass index.  
Data collected from imaging performed as part of standard clinical care should include left ventricular 
ejection fraction, diastolic function (including average E/E’), significant valvular disease (defined as at 
least moderate stenosis or regurgitation), left atrial diameter, left atrial volume (including indexed for 
body surface area), and presence of significant coronary disease at angiography (invasive or CT)(if 
performed).  
Laboratory test results recorded should include haemoglobin, urea, creatinine, and creatinine clearance 
(estimated by Cockroft and Gault formula).  

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A 12 lead ECG should be performed. 
7.5. Pre-procedure cardiac MRI 
Those participants who are undergoing elective AcQMap guided ablation will undergo a cardiac MRI (3 
Tesla) within the 6 weeks prior to the catheter ablation procedure.  
Patients will complete an MRI safety questionnaire (5 min) prior to the scan. An intravenous cannula will 
be inserted. Cardiac MRI will evaluate cardiac structure and function, with particular focus on the left 
atrium. For late gadolinium enhancement imaging, the total dose of gadolinium-based contrast will not 
exceed 0.2mmol/kg. 
The total duration of the MR protocol will be ~60 min, considering ~50 min of scanning time, plus ~10 
min for pre-/post-scan preparation. 
7.6. Study visit (control group) 
As part of standard care, a 12 lead ECG will be performed for all patients following arrival on the day of 
their procedure. 
Venous access, placement of electrophysiology catheters, and completion of diagnostic 
electrophysiology study will be undertaken in line with standard clinical care. Trans-septal puncture for 
left atrial access will be undertaken and anticoagulation will be administered in line with standard 
protocols. Prior to any ablation, left atrial electroanatomical voltage mapping (EAVM) using the Abbott 
Advisor HD Grid (SE) mapping catheter using the orthogonal wave setting (HD wave solution) will then be 
undertaken. This will be conducted during bipolar pacing from the mid point of the coronary sinus 
catheter at a cycle length of 800ms for 4 beats followed by a single extrastimulus with coupling interval 
of 300ms. Care must be taken to keep the catheter in each position to record all 5 cycles before moving 
to acquire new points aiming for a minimum of 300 points in total with full and equal covering of the 
atrial surface. Interpolation threshold should be set to 7mm with points filtered to within 5mm of the 
surface anatomy (interior and exterior projection). Initial map collection should be specified as a CFAE 
map set to collect points with the catheter stationary for 5 seconds. 
Following completion of the EAVM, the procedure continues in line with standard clinical practice. If, for 
any reason the EAVM is not performed then the patient will be removed from the study. If mapping has 
commenced but is incomplete then the data will still be used. 
7.7. Study visit (excluding control group) 
As part of standard care, a 12 lead ECG will be performed for all patients following arrival on the day of 
their procedure. In line with standard practice in this institution all procedures will be undertaken under 
general anaesthesia.  
Venous access, trans-septal puncture and placement of standard electrophysiology catheters will be 
undertaken as per standard clinical care. Anticoagulation will be administered following trans-septal 
puncture in line with standard protocols.  
Please see appendix A for detailed study flow chart. 
All patients 

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All study patients will undergo electroanatomical voltage mapping (EAVM) using the Abbott Advisor HD 
Grid (SE) mapping catheter using the orthogonal wave setting (HD wave solution) in the same manner as 
described above. If in AF at the start of the procedure direct current cardioversion (DCCV) will be used to 
restore sinus rhythm. This can be repeated at the discretion of the operator if initially unsuccessful 
(including internal cardioversion if necessary). If unsuccessful then the patient will no longer be included 
in the study and the procedure should continue according to standard clinical care.  
Mapping will then be undertaken during bipolar pacing from the mid point of the coronary sinus catheter 
at a cycle length of 800ms for 4 beats followed by a single extrastimulus with coupling interval of 300ms 
(or the shortest captured cycle length if longer). Atrial geometry can be acquired concurrently. Care must 
be taken to keep the catheter in each position to record all 5 cycles before moving to acquire new points 
aiming for a minimum of 300 points in total with full and equal covering of the atrial surface. 
Interpolation threshold should be set to 7mm with points filtered to within 5mm of the surface anatomy 
(interior and exterior projection). Initial map collection should be specified as a CFAE map set to collect 
points with the catheter stationary for 5 seconds. Subsequent analyses offline will use the Precision 
turbomap feature to adjust the data displayed. Ablation and the rest of the procedure can then be 
performed according to standard clinical practice. 
Post procedure care including subsequent discharge will continue in line with standard clinical practice.  
Subgroup undergoing contact force guided mapping 
20 patients undergoing AF ablation will have a further map completed using a contact force guided 
bipolar irrigated ablation catheter (Abbott Tacticath) during the same pacing protocol. For all voltage 
maps a minimum of 300 points should be obtained with full and equal covering of the atrial surface, 
interpolation should be set to 7mm, and set to only include points with contact force between 5 and 
50grams. 
Subgroup undergoing AcQMap guided mapping and ablation 
10 patients with persistent AF who are undergoing AcQMap guided elective catheter ablation 
procedures will be included in this sub-study. All patients will undergo the same main study mapping 
procedure outlined above. In addition, AcQMap recordings will also be obtained. Recordings will be 
made during pacing with the same main study protocol and two 30 second recordings will be undertaken 
during AF. HD grid contact recordings will then also be obtained in regions of prominent rotational and 
irregular conduction identified by AcQMap and ablation performed at the operator’s discretion. 
For patients presenting in sinus rhythm or AF, all required mapping should be completed in the 
presenting rhythm followed by either AF induction (using incremental burst atrial pacing) or DCCV 
respectively before completion of mapping procedures. Ablation in line with standard clinical care will be 
undertaken following completion of all mapping procedures. 
For an outline of study procedures versus standard care and estimated time requirements, please see 
appendix B. 
7.8. Follow up 

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Participants will be seen post procedure prior to discharge to exclude any adverse events. This will 
represent the end of the study. No further research follow up is required for most but routine clinical 
follow up will take place including participant access to arrhythmia specialist nurse practitioners. 
Participants undergoing AcQMap guided ablation and cardiac MRI will undergo a repeat cardiac MRI 3-6 
months after the procedure. This will be planned wherever possible to take place at the same time as 
attending for routine clinical follow up after the procedure. 
7.9. Discontinuation/Withdrawal of Participants from Study 
Each participant has the right to withdraw from the trial at any time.  In addition, the Investigator may 
discontinue a participant from the trial at any time if the Investigator considers it necessary for any 
reason including: 
• 
Pregnancy 
• 
Ineligibility (either arising during the trial or retrospectively having been overlooked at screening) 
• 
Significant protocol deviation 
• 
An adverse event which requires discontinuation of the catheter ablation or results in inability to 
continue to comply with trial procedures 
• 
Withdrawal of Consent 
If a patient is withdrawn or voluntarily withdraws from the trial prior to the study procedure then all 
study data collected will be excluded and they will be replaced in the study. If any event during the 
procedure results in necessary deviation from the study protocol on grounds of clinical necessity then 
any data collected up to that point will be analysed. It may be required to recruit additional patients if 
this occurs depending on the extent to which data had been collected. This is at the discretion of the 
chief investigator. 
The reason for withdrawal will be recorded in the CRF. 
7.10. 
Definition of End of Study 
The end of the study is defined as the end of the study procedure for the last study participant. 
8. SAFETY REPORTING 
8.1. Definition of Serious Adverse Events 
A serious adverse event is any untoward medical occurrence that: 
• 
results in death 
• 
is life-threatening 
• 
requires inpatient hospitalisation or prolongation of existing hospitalisation 
• 
results in persistent or significant disability/incapacity 
• 
consists of a congenital anomaly or birth defect. 
Other ‘important medical events’ may also be considered serious if they jeopardise the participant or 
require an intervention to prevent one of the above consequences. 

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NOTE: The term "life-threatening" in the definition of "serious" refers to an event in which the 
participant 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. 
8.2. Reporting Procedures for Serious Adverse Events 
A serious adverse event (SAE) occurring to a participant should be reported to the REC that gave a 
favourable opinion of the study where in the opinion of the Chief Investigator the event was ‘related’ 
(resulted from administration of any of the research procedures) and ‘unexpected’ in relation to those 
procedures. Reports of related and unexpected SAEs should be submitted within 15 working days of the 
Chief Investigator becoming aware of the event, using the HRA report of serious adverse event form (see 
HRA website). 
9. STATISTICS AND ANALYSIS 
9.1. Description of Statistical Methods 
This is a mechanistic study exploring a change in electrogram morphology. This will be expressed as a 
proportion of signals recorded within each amplitude bracket. Statistical comparisons using the chi-
square tests of 2 proportions will be made to look for significant differences at long and short cycle 
length.   
In the sub-study comparing voltage mapping methods, simple statistical analysis will be used to compare 
voltage amplitudes obtained by each method in sinus rhythm and in AF. Means will be compared using 
independent sample t-test.  
Retrospective analyses may be conducted to explore trends in electrophysiological mechanisms 
identified and their relation to demographic, anatomical, or clinical features recorded and in line with 
secondary outcome measures. 
9.2. The Number of Participants 
The total number of participants will be 35; 30 with AF and 5 controls. Previous studies have revealed the 
presence of low voltage areas (<0.5mV) in approximately 35% of patients with persistent AF undergoing 
catheter ablation,(7) and in the one previous prospective study of patients without low voltage areas, 
intermediate amplitude regions were observed in 43%.(9) Our hypothesis is that conduction properties, 
and thus electrogram morphology will become abnormal at shorter cycle length. A sample of 35 is 
consistent with previous mechanistic exploratory studies and should include enough patients with 
regions of voltage amplitude <1.1mV according to prior results outlined above and allow comparisons 
between each cycle length. As this is an exploratory study we are not evaluating a specific intervention, 
formal power calculations have limited usefulness. 
The control group will consist of 5 patients with presumed normal atria. Although this is a small number, 
a high number of points will be collected to allow good distribution of results. By analysing the combined 
total electrogram recordings and excluding patients with any risk factors for abnormal atrial substrate 
then this sample should provide adequate estimation of normal values. 

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9.3. Analysis of Outcome Measures 
Control group: 
All electrogram samples will be analysed at baseline (long) cycle length and classified as normal or 
abnormal (see above definitions in section 4). The same sampling points will then be analysed at short 
cycle length and classified in the same way. The proportion of electrograms changing from normal to 
abnormal will be recorded as will the change in electrogram amplitude and duration. 
The whole chamber mean, median and distribution of voltage amplitude at long cycle length will be 
analysed. This will also be done for each atrial segment. The segment with the lowest mean amplitude 
will be identified and the cut-off for the value representing the upper 95% of recordings in that segment 
calculated. This will be used as the value representing the lower limit of normal for subsequent study 
analyses.  
All participants: 
All electrogram samples will be analysed at baseline (long) cycle length and classified as normal or 
abnormal (see above definitions in section 4). The same sampling points will then be analysed at short 
cycle length and classified in the same way. The proportion of electrograms classified as normal and 
abnormal at each cycle length will be calculated for the full sample set and according to baseline 
electrogram amplitude (<0.5mV, 0.5-lower limit of normal, and >lower limit of normal)(lower limit of 
normal defined above from analysis of the control group). 
For each participant, conduction velocities will be analysed in regions of different baseline electrogram 
amplitude at both long and short cycle length. This will be done using the Turbomap feature in Precision 
to create an activation map (specified as measuring on maximum negative dV/dt). Conduction velocity 
will be calculated as a mean of 5 measurements using the difference in activation times between 2 
points in a straight line at set distance through the region of least isochronal crowding. This will be done 
in regions of low, intermediate and preserved voltage at long and short cycle length. 
The outcome measures will be assessed in all patients in whom the study procedure was performed. 
Voltage mapping subgroup: 
For all maps obtained in this subgroup using both the HD grid and ablation catheter, bipolar voltage 
amplitudes will be compared. Mean amplitudes will be compared for the entire chamber and each atrial 
segment (anterior, septal, inferior wall, posterior wall, roof, lateral wall). Each sampling point obtained 
using the ablation catheter in sinus rhythm/baseline pacing cycle length will then be compared to an 
equivalent nearest point obtained by the HD grid in sinus rhythm/baseline pacing cycle length to give a 
difference (+/-) in amplitude recorded. Mean differences will be compared for the whole atrium and 
each segment as outlined above. 
The outcome measures will be assessed in all patients in whom the study procedure was performed. 
AcQMap subgroup: 
Qualitative and quantitative assessments of conduction patterns identified on AcQMap during AF will be 
made with regions of frequent focal firing, slow conduction, rotational activation or irregular activation 
identified (according to AcQTrack and visual interpretation of the operator in line with and according to 

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their prior experience). Contact electrograms using the HD grid will be recorded at these regions and 
classified according to their degree of fractionation. Regions identified as above by the operator will be 
compared to the rest of the atria according to sinus rhythm voltage amplitude and proportional change 
in electrogram morphology and conduction velocity with changing pacing cycle length. 
The outcome measures will be assessed in all patients in whom the study procedure was performed. 
10. DATA MANAGEMENT 
10.1. 
Access to Data 
Direct access will be granted to authorised representatives from the Sponsor and host institution for 
monitoring and/or audit of the study to ensure compliance with regulations. 
10.2. 
Data Recording and Record Keeping 
The participants will be identified by a unique trial specific number and/or code in any database.  The 
name and any other identifying detail will NOT be included in any trial data electronic file. A paper form 
assigning patient details to study codes will be kept in the study master file only. 
Electroanatomical mapping data forms the majority of study data collected. Participants will be identified 
by their unique trial number on any data exported from the catheter laboratory computers. All clinical 
procedure data will be stored on secure trust servers in a password-protected folder in line with 
standard practice for all such clinical procedures. AcQMap data is stored on a designated ACUTUS 
workstation on which all clinical cases are stored. Study data for analysis will be exported at the time of 
the procedure in an anonymised form identifiable by study code onto separate computer workstations 
to allow analysis of the mapping data. Analysis work is done within the research office using these 
designated systems, which are password protected and accessible by the study team only.  
Analysis results will then be recorded using a purpose designed Excel database. 
Data will be retained for 5 years after the end of the study. 
11. QUALITY ASSURANCE PROCEDURES 
The study may be monitored, or audited in accordance with the current approved protocol, GCP, 
relevant regulations and standard operating procedures. 
12. ETHICAL AND REGULATORY CONSIDERATIONS 
12.1. 
Declaration of Helsinki 
The Investigator will ensure that this study is conducted in accordance with the principles of the 
Declaration of Helsinki. 
12.2. 
Guidelines for Good Clinical Practice 

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The Investigator will ensure that this study is conducted in accordance with relevant regulations and with 
Good Clinical Practice. 
12.3. 
Approvals 
The protocol, informed consent form, participant information sheet and any proposed advertising 
material will be submitted to an appropriate Research Ethics Committee (REC), and HRA for written 
approval. 
The Investigator will submit and, where necessary, obtain approval from the above parties for all 
substantial amendments to the original approved documents. 
12.4. 
Reporting 
The CI shall submit once a year throughout the study, or on request, an Annual Progress report to the 
REC Committee, HRA (where required) host organisation and Sponsor. In addition, an End of Study 
notification and final report will be submitted to the same parties. 
12.5. 
Participant Confidentiality 
The trial staff will ensure that the participants’ anonymity is maintained.  The participants will be 
identified only by a participant ID number on all trial documents and any electronic database, with the 
exception of the CRF, where participant initials may be added.  All documents will be stored securely and 
only accessible by trial staff and authorised personnel. The trial will comply with the Data Protection Act, 
which requires data to be anonymised as soon as it is practical to do so. 
12.1. 
Expenses and Benefits 
Reasonable travel expenses for any visits additional to normal care will be reimbursed on production of 
receipts, or a mileage allowance provided as appropriate. 
12.2. 
Cardiac MRI 
MRI is a safe and non-invasive technique with no known risk when appropriately supervised. It does not 
involve ionizing radiation (X-rays). Potential participants with ferromagnetic objects in their bodies or 
with implanted devices which can be damaged by the CMR magnet will be excluded by carefully 
screening all participants for ferromagnetic objects, metal implants and other metal (e.g. shrapnel injury) 
every time prior to entering the scanner environment.  OCMR is fully equipped for resuscitation 
(including defibrillation) in the unlikely event of a medical emergency during scanning. Either Advanced-
Life-Support trained clinicians or Intermediate-Life-Support trained radiographers will be performing MRI 
scans in study participants.  
While most people do not experience discomfort in a MRI environment, the enclosed space of the 
scanner can potentially feel uncomfortable. Discomfort from lying still for a long period of time will be 
minimized with comfortable padding and positioning. People with a history of claustrophobia would be 
excluded from participation in the study. Participants will be given a chance to see the scanner before 
the study starts.  Whilst in the scanner, participants are able to use the alarm button or can squeeze a 
bulb placed in their hands if they wish to communicate with the operator or to interrupt the scanning at 
any stage of the scanning process. As the MRI scanner is noisy, participants would be fitted with ear-

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plugs and/or acoustically shielded headphones to minimize the noise and aid communication between 
participants and investigators.   
Once contraindications to magnetic resonance imaging are excluded by use of the facility’s screening 
forms, the risks of undergoing a scan are minimal.  A trained scanner operator or radiographer will go 
through a list of possible risks with the participant before scanning.  The MRI scanner consists of a large 
powerful magnet.  Magnetic resonance imaging uses no ionizing radiation.  There are, however, 
potential hazards associated with MRI and the scanning of participants including the presence of surgical 
implants, participants’ clothing, jewellery (such as body piercings) bodily habitus, or medical conditions.  
A comprehensive list of potential risks has been compiled, and the participant should be checked against 
this by the operator, prior to entering the controlled areas of the MRI scanners.  Participants will be 
asked to wear a gown for the CMR scans that preserves their modesty while remaining loose in the 
scanner to avoid potential burns from synthetic clothing. To help maintain participant dignity they will be 
asked to leave their underwear on, so long as it is not made of synthetic material and has no metal parts 
(e.g. zips, bras clasps or studs). Participants will be asked to change in a changing room near to the 
scanner and will be given a locker to securely store their belongings. If they are unable to change into the 
gown by themselves a member of staff will be on hand to aid. 
Gadolinium contrast is widely used for clinical indications in CMR and is safe. Occasionally it may cause a 
mild headache, nausea, itching and very rarely (< 1 in 5000) a more severe allergic reaction. It is cleared 
within hours by the body. Gadolinium has recently been associated with nephrogenic systemic fibrosis in 
patients with severe renal dysfunction; hence, as per departmental guidelines, based on Food and Drug 
Administration guidelines, all patients with glomerular filtration rate (GFR) < 30 ml/min (stage 3-5 renal 
disease) should not be given gadolinium. For this study, all potential participants with a GFR < 30 ml/min 
will be excluded (see Exclusion Criteria). It is known that small amounts of gadolinium deposits can 
remain in the body, including the skin, bones and the brain. There has been no scientific evidence to-
date that these gadolinium deposits are harmful or lead to adverse health effects, although this is an 
active area of research. 
The current study is wholly research-oriented, and the images of the heart are for specific research 
purposes only, and are not suitable for diagnostic opinions. However, although the images are not 
diagnostic scans, in the event of an abnormality of clear clinical relevance being noted incidentally, a 
designated clinical specialist would discuss the implications with the patient and arrange for further 
investigations as necessary. 
13. FINANCE AND INSURANCE 
13.1. 
Funding 
Funding is secured through a competitive grant awarded by the Oxfordshire Health Services Research 
Committee (OHSRC) and through departmental research budgets (CRM Hub). 
13.2. 
Insurance 
NHS bodies are legally liable for the negligent acts and omissions of their employees. If you are harmed 
whilst taking part in a clinical research study as a result of negligence on the part of a member of the 
study team this liability cover would apply. 
Non-negligent harm is not covered by the NHS indemnity scheme. The Oxford University Hospitals NHS 
Foundation Trust, therefore, cannot agree in advance to pay compensation in these circumstances. 

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In exceptional circumstances an ex-gratia payment may be offered. 
14. PUBLICATION POLICY 
The results will be presented at scientific meetings and published in peer-reviewed scientific journals. 
The Investigators will be involved in reviewing drafts of the manuscripts, abstracts, press releases and 
any other publications arising from the study.  Authors will acknowledge that The Oxfordshire Health 
Services Research Committee, part of Oxford Hospitals Charity, funded the study). Authorship will be 
determined in accordance with the ICMJE guidelines and other contributors will be acknowledged. 
Participating patients will be offered a copy of any publications arising from the study. 
15. REFERENCES 
1. 
Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA, et al. 2012 HRS/EHRA/ECAS expert 
consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient 
selection, procedural techniques, patient management and follow-up, definitions, endpoints, and 
research trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical 
Ablation of Atrial Fibrillation. Developed in partnership with the European Heart Rhythm Association 
(EHRA), a registered branch of the European Society of Cardiology (ESC) and the European Cardiac 
Arrhythmia Society (ECAS); and in collaboration with the American College of Cardiology (ACC), American 
Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the Society of Thoracic 
Surgeons (STS). Endorsed by the governing bodies of the American College of Cardiology Foundation, the 
American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm 
Association, the Society of Thoracic Surgeons, the Asia Pacific Heart Rhythm Society, and the Heart 
Rhythm Society. Heart Rhythm. 2012;9(4):632-96.e21. 
2. 
Gökoğlan Y, Mohanty S, Güneş MF, Trivedi C, Santangeli P, Gianni C, et al. Pulmonary Vein 
Antrum Isolation in Patients With Paroxysmal Atrial Fibrillation: More Than a Decade of Follow-Up. Circ 
Arrhythm Electrophysiol. 2016;9(5). 
3. 
Tutuianu C, Szilagy J, Pap R, Sághy L. Very Long-Term Results Of Atrial Fibrillation Ablation 
Confirm That This Therapy Is Really Effective. J Atr Fibrillation. 2015;8(2):1226. 
4. 
Wynn GJ, Das M, Bonnett LJ, Panikker S, Wong T, Gupta D. Efficacy of catheter ablation for 
persistent atrial fibrillation: a systematic review and meta-analysis of evidence from randomized and 
nonrandomized controlled trials. Circ Arrhythm Electrophysiol. 2014;7(5):841-52. 
5. 
Verma A, Jiang CY, Betts TR, Chen J, Deisenhofer I, Mantovan R, et al. Approaches to catheter 
ablation for persistent atrial fibrillation. N Engl J Med. 2015;372(19):1812-22. 
6. 
Rolf S, Hindricks G, Sommer P, Richter S, Arya A, Bollmann A, et al. Electroanatomical mapping of 
atrial fibrillation: Review of the current techniques and advances. J Atr Fibrillation. 2014;7(4):1140. 
7. 
Rolf S, Kircher S, Arya A, Eitel C, Sommer P, Richter S, et al. Tailored atrial substrate modification 
based on low-voltage areas in catheter ablation of atrial fibrillation. Circ Arrhythm Electrophysiol. 
2014;7(5):825-33. 
8. 
Verma A, Wazni OM, Marrouche NF, Martin DO, Kilicaslan F, Minor S, et al. Pre-existent left atrial 
scarring in patients undergoing pulmonary vein antrum isolation: an independent predictor of procedural 
failure. J Am Coll Cardiol. 2005;45(2):285-92. 
9. 
Yagishita A, Sparano D, Cakulev I, Gimbel JR, Phelan T, Mustafa H, et al. Identification and 
electrophysiological characterization of early left atrial structural remodeling as a predictor for atrial 
fibrillation recurrence after pulmonary vein isolation. J Cardiovasc Electrophysiol. 2017;28(6):642-50. 
10. 
Lin Y, Yang B, Garcia FC, Ju W, Zhang F, Chen H, et al. Comparison of left atrial electrophysiologic 
abnormalities during sinus rhythm in patients with different type of atrial fibrillation. J Interv Card 
Electrophysiol. 2014;39(1):57-67. 
11. 
Jadidi AS, Cochet H, Shah AJ, Kim SJ, Duncan E, Miyazaki S, et al. Inverse relationship between 
fractionated electrograms and atrial fibrosis in persistent atrial fibrillation: combined magnetic 

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resonance imaging and high-density mapping. J Am Coll Cardiol. 2013;62(9):802-12. 
12. 
Haissaguerre M, Shah AJ, Cochet H, Hocini M, Dubois R, Efimov I, et al. Intermittent drivers 
anchoring to structural heterogeneities as a major pathophysiological mechanism of human persistent 
atrial fibrillation. J Physiol. 2016;594(9):2387-98. 
13. 
Yang B, Jiang C, Lin Y, Yang G, Chu H, Cai H, et al. STABLE-SR (Electrophysiological Substrate 
Ablation in the Left Atrium During Sinus Rhythm) for the Treatment of Nonparoxysmal Atrial Fibrillation: 
A Prospective, Multicenter Randomized Clinical Trial. Circ Arrhythm Electrophysiol. 2017;10(11). 
14. 
Marrouche NF, Wilber D, Hindricks G, Jais P, Akoum N, Marchlinski F, et al. Association of atrial 
tissue fibrosis identified by delayed enhancement MRI and atrial fibrillation catheter ablation: the 
DECAAF study. JAMA. 2014;311(5):498-506. 
15. 
Mahnkopf C, Badger TJ, Burgon NS, Daccarett M, Haslam TS, Badger CT, et al. Evaluation of the 
left atrial substrate in patients with lone atrial fibrillation using delayed-enhanced MRI: implications for 
disease progression and response to catheter ablation. Heart Rhythm. 2010;7(10):1475-81. 
16. 
Miyamoto K, Tsuchiya T, Narita S, Yamaguchi T, Nagamoto Y, Ando S, et al. Bipolar electrogram 
amplitudes in the left atrium are related to local conduction velocity in patients with atrial fibrillation. 
Europace. 2009;11(12):1597-605. 
 
 

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16. APPENDIX A:  PARTICIPANT GROUP ALLOCATION AND STUDY FLOW CHART 
 
 
ALL PATIENTS 
Baseline recordings during pacing 
SVT GROUP 
5 patients 
AF ABLATION GROUP 
30 patients 
Continue with 
standard procedure 
Additional 
recordings using 
ablation catheter 
20 patients  
Additional 
recordings using 
AcQMap catheter 
10 patients  
Continue with 
standard 
procedure 
Continue with 
standard 
procedure 

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All 
patients 
Continue 
standard 
clinical 
procedure 
Attend in 
sinus 
rhythm 
Ablation 
catheter 
mapping 
subgroup 
DCCV 
(procedure 
at operator’s 
discretion) 
AcQMap 
subgroup 
Voltage map 
using Tacticath 
pacing 
AcQMap 
recording of AF 
with HD grid 
recording in 
regions specified 
by operator 
Attend 
in AF 
HD grid map 
during 
pacing 
Induce AF 
AcQMap recording 
of AF with HD grid 
recording in 
regions specified 
by operator 
DCCV 
(procedure at 
operator’s 
discretion) 
AcQMap and HD 
grid mapping 
during pacing 
protocol 
DCCV 
(procedure at 
operator’s 
discretion) 

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17. APPENDIX B: Table distinguishing routine and study procedures and estimated additional 
time requirements 
 
 
 
 
 
Standard care 
Research procedure 
All elective AF 
ablation 
patients 
AcQMap 
guided AF 
ablation 
patients 
Left sided 
accessory 
pathway 
ablation 
5 control 
patients 
30 AF patients 
Contact-force 
mapping 
subgroup 
AcQMap 
guided 
subgroup 
Venous access 
and insertion of 
electrophysiolo
gical catheters 
and trans-
septal puncture 
Additional 
venous access 
and insertion 
of AcQMap 
catheter 
Venous access 
and insertion 
of 
electrophysiol
ogical 
catheters 
Specified left 
atrial 3-
dimensional 
mapping using 
HD grid and 
specified 
study protocol 
(Additional 
time estimate 
= 20 minutes) 
Specified 
pacing map 
during initial 
left atrial 3-
dimensional 
mapping and 
geometry 
acquisition 
using HD grid 
(Additional 
time estimate 
= 10 mins) 
Additional 
ablation 
catheter map 
during pacing 
(Additional 
time estimate 
= 15 minutes) 
 
 
AcQMap 
recording 
during pacing 
(Additional 
time estimate 
= 5 minutes) 
Standard 3-
dimensional 
left atrial 
geometry 
acquisition and 
contact 
mapping using 
a multipolar 
mapping 
catheter  
AcQMap 
mapping of AF 
(left +/- right 
atrium 
Trans-septal 
puncture 
HD grid 
catheter 
evaluation of 
regions with 
specified 
activation 
patterns 
(Additional 
time estimate 
= 10 minutes) 
Direct current 
cardioversion 
(if clinically 
required) 
Additional left 
+/- right atrial 
ablation 
Diagnostic EP 
study 
Left atrial 
ablation 
including 
pulmonary vein 
isolation  
Accessory 
pathway 
mapping and 
ablation 
Total additional time estimates for each study 
group 
20 minutes 
10 minutes 
15 minutes 
15 minutes 

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18. APPENDIX B:  SCHEDULE OF STUDY PROCEDURES 
Procedures 
(all participants) 
Visits 
 
Prior to procedure* 
Study visit 
Screening Baseline  
Prior to 
procedure 
During 
procedure 
Prior to 
discharge 
At ~3-6 
months 
Informed consent 
√ 
 
 
 
 
 
Eligibility 
assessment 
√ 
 
 
 
 
 
Demographics 
√ 
 
 
 
 
 
Medical history 
√ 
 
 
 
 
 
Concomitant 
medications 
 
√ 
√ 
 
 
 
Height, weight, 
BMI 
 
√ 
 
 
 
 
Imaging results 
 
√ 
 
 
 
 
12 lead ECG 
 
√ 
√ 
 
√ 
 
Laboratory test 
results 
 
√ 
 
 
 
 
HD grid mapping 
at long and short 
cycle length 
 
 
 
√ 
 
 
Adverse event 
assessments  
 
 
 
 
√ 
 
20 Ablation 
catheter 
mapping patients 
 
 
Additional 
mapping with HD 
grid and ablation 
catheter 
 
 
 
√ 
 
 
10 AcQMap 
patients 
 
 
AcQMap AF 
recording and HD 
grid contact 
electrogram 
acquisition 
 
 
 
√ 
 
 
MRI Scan 1 
 
√ 
 
 
 
 
MRI Scan 2 
 
 
 
 
 
√ 
*May be carried out when attending for the elective procedure but prior to the procedure taking place 
providing that all information has been provided to the prospective participant well in advance to 
allow them to fully consider involvement and they are not undergoing AcQMap guided procedures and 
cardiac MRI. 

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19. APPENDIX C:  AMENDMENT HISTORY 
 
Amendment 
No. 
Protocol 
Version 
No. 
Date 
issued 
Author(s) of changes 
Details of Changes made