A Prospective Multi-centre Study of Effectiveness of Ripple Mapping for Atrial Tachycardia Ablation
Phase: NA
Conditions: Atrial Tachycardia
Sponsor: Imperial College London

 
 
 
 
 
 
 
 
A PROSPECTIVE MULTI-CENTRE STUDY OF EFFECTIVENESS OF RIPPLE 
MAPPING FOR ATRIAL TACHYCARDIA ABLATION 
 
Ripple AT 
JRCO and insurance reference: 14HH2319 
 
Protocol - Version 1.1 (13th February 2015) 
Study Sponsor: Imperial College Healthcare NHS Trust 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
STUDY COORDINATION CENTRE: Hammersmith Hospital Campus, Imperial College 
Healthcare, London 
 
Study Management Group  
Chief investigator: Dr Prapa Kanagaratnam 
Co-investigator: Dr Vishal Luther  
Co-investigator: Dr Nick Linton 
 
 
Clinical Queries  
For general queries, supply of study documentation and collection of data please contact co-
investigator 
 
Dr Vishal Luther 
v.luther14@imperial.ac.uk 
Hammersmith hospital 
 
150 Du Cane Road 
London 
W12 OHS 
Tel: +44 7828913612 
 
Sponsor  
Imperial College Healthcare NHS Trust 
 
This protocol describes the Ripple AT study and provides information about procedures for 
entering participants. Every care was taken in its drafting, but corrections and amendments 
may be necessary. These will be circulated to the 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 NHS Research Governance 
Framework for Health and Social Care (2nd Edition). It will be conducted in compliance with 
the protocol, the Data Protection Act and other regulatory requirements as appropriate. 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
CONTENTS 
 
1.1 INTRODUCTION 
1.2 HYPOTHESIS 
2. STUDY DESIGN  
2.1 SITE SELECTION CRITERIA 
2.2 RANDOMISATION 
2.3 MAPPING PROTOCOL 
2.3.1 Generalized approach 
2.3.2 GROUP 1 (RIPPLE MAPPING) 
2.3.2.1 Collecting Data for Ripple Mapping 
2.3.2.1.1 Map Setup and Map Collection:  
2.3.2.1.2 ConfiDENSE:  
2.3.2.1.3 Which chamber to map first?   
2.3.2.2 The CARTO Ripple Map user interface 
2.3.2.2.1 Ripple Map Preferences:  
2.3.2.2.2 Ripple Cine Player (Map>Ripple Map>Play):  
2.3.2.2.3 Ripple Viewer (Window > Ripple Viewer):  
2.3.2.3 Analysing a Ripple Map 
2.3.2.3.1 Set up Ripple Viewer to display multiples of full 
tachycardia cycle length:  
  
 
 
 
2.3.2.3.2 Set up Ripple Preferences and Ripple Cine Player:  
2.3.2.3.3 Dynamic Scar Thresholding:  
2.3.2.3.4 Review Chamber in multiple orientations.  
2.3.2.3.5 Use of design lines:   
2.3.2.3.5 Importing old studies:   
2.3.2.4 Avoiding errors with a Ripple Map 
2.3.4 GROUP 2 (CARTO ISOCHRONAL ACTIVATION MAP) 
2.3.5 Categorisation of maps 
3 STUDY OUTCOME MEASURES 
3.1 Post ablation map in patients with any linear lesion sets:  
3.2 FOLLOW UP 
4.  DATA ANALYSIS 
5. PARTICIPANT ENTRY  
5.1 PRE-REGISTRATION EVALUATIONS  
5.2 INCLUSION CRITERIA 
5.3 EXCLUSION CRITERIA  
5.4 WITHDRAWAL CRITERIA 
6. ADVERSE EVENTS  
6.1 DEFINITIONS  
6.2 REPORTING PROCEDURES  
6.2.1 Non serious AEs  
6.2.2 Serious AEs  
7. STATISTICS 
8. DATA MANAGEMENT AND QUALITY CONTROL 
9. REGULATORY ISSUES  
9.1 ETHICS APPROVAL  
9.2 CONSENT  
9.3 CONFIDENTIALITY 
9.4 INDEMNITY  
9.5 SPONSOR  

 
GLOSSARY OF ABBREVIATIONS 
 
3D 
: 
3-Dimensional 
AE 
: 
Adverse Event 
bpm 
: 
Beats per minute 
DSMB 
: 
Data & Safety Monitoring Board 
eCRF 
: 
Electronic Case Report Form 
ECG 
: 
Electrocardiogram 
GCP 
: 
Good Clinical Practice 
ICTU 
: 
Imperial College Trials Unit 
LA 
: 
Left Atrium 
ms 
: 
Milliseconds 
mV 
: 
Millivolts  
NA 
: 
Not applicable 
NHS 
: 
National Health Service 
R&D   
: 
Research and Development 
SAE 
: 
Serious Adverse Event 
sec 
: 
Seconds 
SSA 
: 
Site Specific Assessment 
SVT 
: 
Supraventricular tachycardia 
UADE 
: 
Unanticipated Adverse Device Effect 
W 
:  Watts 
RM 
     :      Ripple Mapping 
AT              :      Atrial tachycardia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
Ripple - AT Protocol Summary 
SPONSOR  
 
 
Imperial College Healthcare NHS Trust 
PROTOCOL TITLE  
A PROSPECTIVE MULTI-CENTRE STUDY OF EFFECTIVENESS OF RIPPLE 
MAPPING FOR ATRIAL TACHYCARDIA ABLATION 
STUDY HYPOTHESIS 
Ripple Mapping is superior to isochronal activation mapping in 
diagnosing the mechanism of atrial tachycardia and guiding the 
delivery of radiofrequency ablation. 
STUDY DESIGN   
 
Multicentre, prospective randomised clinical trial 
TREATMENT REGIMEN  
Randomisation to Ripple Mapping guided AT ablation vs. 
conventional AT ablation.   
INCLUSION CRITERIA 
1. Patients undergoing clinically indicated ablation of sustained atrial 
tachycardia (post AF ablation) using 3D mapping. 
2. Signed informed consent 
 
 
EXCLUSION CRITERIA  
1. Patients with typical flutter.  
2. Patient with non-sustained atrial tachycardia 
3. Contraindication to catheter ablation 
4. Unable to give informed consent 
 
NUMBER OF PATIENTS   
~100 patients, 1:1 randomisation 
NUMBER OF SITES:  
 
7 
Site Selection Criteria 
To perform 4-5 consecutive Ripple mapping guided AT ablations. 
PRIMARY ENDPOINT  
1) Tachycardia change/termination with first ablation set after map 
categorisation. 
SECONDARY ENDPOINT 
1) Tachycardia change/termination during point collection 
2) Tachycardia change/termination during pacing manuoevre 
 
 
 
 
3) Failure to ablate/ change tachycardia with ablation.   
 
 
 
 
 
4) The need for entrainment mapping 
 
 
 
 
 
 
 
 

 
 
 
1.1 INTRODUCTION 
The difficulties of using electroanatomical mapping systems in the diagnosis and treatment 
of atrial tachycardias are widely recognised and result from several factors, including 
inappropriate setting of the “window of interest” in relation to a reference time point, mis-
annotation of signals within that window and misinterpretation of the resultant color-coded 
map.  Ripple Mapping (RM) as a novel 3D mapping system that has the advantage of not 
needing to set a “window of interest”, avoids interpolation between points and minimises 
user post-processing (Linton et al. 2009). 
 
The RM system has been described in detail previously and displays each electrogram at its 
corresponding 3D coordinate on the surface of the cardiac chamber as a dynamic bar that 
changes in length according to the electrogram voltage–time relationship (Linton et al. 
2009). Each point is time-gated to a selected fiduciary reference electrogram and can be 
superimposed on a surface bipolar voltage map identifying any scar. Importantly RM does 
not need LAT annotation as direction of activation is visualised by the relative motion of 
each ripple bar. 
 
An off-line prototype RM system incorporated with CARTO-XP™ was validated using atrial 
tachycardia and demonstrated that experienced CARTO users had improved diagnostic yield 
using RM for the first time compared to standard CARTO activation maps (80% vs 50%) 
without any other EP data (Jamil-Copley et al. 2013).   
 
The residual error rate of 20% in the RM group was higher than expected.  This was thought 
to be related to several standard CARTO based approaches to data collection and 
interpretation being inadequate for RM (Koa Wing 2014).  These included: 
1. Insufficient or unevenly distributed points, leaving areas without activation data. 
2. Parts of the activation map not being ‘seen’ due to <100% of cycle length collected. 
3. RMs played using the default bar and scar settings 
 
A standardized diagnostic algorithm to data collection and RM interpretation was developed 
with the aim of minimizing errors and improving diagnostic accuracy (Koa Wing 2014).  
Ripple Mapping is now incorporated in CARTO3 v4, and this algorithm can now be tested 
prospectively. 
 
The AT substrate can demonstrate widespread area of scar around which the wavefront 
propagates.  Using Ripple mapping to combine both voltage and activation data during 
tachycardia identifies isthmuses of tissue (with Ripple bars propagating across) bordered by 
areas of functionally inactive tissue (with no Ripple activity) which may be critical for the 
tachycardia circuit.  In patients with complex atrial substrates, ablation of these isthmuses 

 
identified using Ripple mapping may lead to tachycardia termination in otherwise 
unsuccessful cases. 
 
This study is based on the following observations; 
i) Activation mapping requires accurate assignment of local activation times. 
ii) Activation mapping is dependent on an appropriately set window of interest (WOI) 
iii) It is not known how often these potential sources of error lead to operators relying on 
additional pacing manuoevres to make a diagnosis 
iv) It is not known how often ablation is delivered after an inaccurate diagnosis 
v) Conventional mapping leads to difficulties in defining scar. 
v) Ripple mapping is not susceptible to annotation or WOI errors, but operators have to 
interpret moving wavefront. 
 
1.2 HYPOTHESIS 
Ripple Mapping is superior to activation mapping in diagnosing the mechanism of atrial 
tachycardia and guiding the delivery of radiofrequency ablation. 
 
1.3 OBJECTIVE 
To compare the effectiveness of Ripple Mapping against conventional activational mapping 
as determined by: 
1. The operator’s confidence in the diagnosis of the mechanism of atrial tachycardia 
from their first map collected. 
2. The percentage of cases where the tachycardia changes/terminates with first 
ablation set after map categorisation. 
3. The amount of ablation required; the overall procedural time; dependence on 
entrainment mapping to make diagnosis. 
 
2. STUDY DESIGN  
This is a multi-centre prospective open randomised control study of 100pts comparing RM 
guided AT ablation against conventional AT ablation. 
 
2.1 SITE SELECTION CRITERIA 
Centres and investigators will undertake a minimum of 4-5 consecutive Ripple mapping 
guided AT ablations prior to starting the randomized study. These cases will be reviewed 
with the Trial Management team. 
 
2.2 RANDOMISATION 
Patients referred for clinically indicated AT ablation by their electrophysiologist will be 
recruited.  For each patient recruited to the study, they will be block randomized into 2 arms 
- Ripple Mapping guided ablation, or conventional ablation.   
 

 
2.3 MAPPING PROTOCOL 
 
2.3.1 Generalized approach 
Patients will be studied in the post-absorptive state. Trans-oesphageal echo will be used to 
exclude LA thrombus as per local protocol.  Periprocedural anticoagulation will be as per 
local protocol.  Patients will be prepared for AT ablation as per local protocol which may 
include sedation/GA, pressure sensing catheter and deflectable sheaths but must use the 
CARTO 3 Version 4 system for mapping. Each centre can use their preferred radiofrequency 
ablation catheter approach and settings, but this must be same for both groups.  A detailed 
CARTO-3v4™ (Biosense Webster, USA) electroanatomical map will be collected using a 3.5-
mm Navistar Thermocool catheter or LASSO Nav (Biosense, Inc.). 
 
A decapolar catheter will be placed in the coronary sinus and a suitable CS reference is 
selected. The operator may set a window-of-interest suitable for isochronal activation 
mapping if required.   
 
2.3.2 GROUP 1 (RIPPLE MAPPING) 
 
If the CS activation is proximal-distal and the surface ECG is inconsistent with CTI dependent 
flutter, a right atrial map should be generated first. The map should be collected as a bipolar 
voltage map with “Scar auto tagging” turned off.  The isochronal activation map must not be 
seen by the operator. 
 
2.3.2.1 Collecting Data for Ripple Mapping 
Ripple Mapping is most effective with raw data collected evenly throughout the whole 
chamber-of-interest so that activation can be visualised globally during the whole cycle 
length.  The introduction of multipolar mapping and the ability to acquire several hundred 
points within a short period of time has facilitated the process of creating a high density 
map. Importantly, in post-AF ablation tachycardias where the substrate is complex, it is 
important to understand activation patterns within scarred region. Most operators will not 
usually collect a high density of points within scar as these are difficult to annotate but with 
Ripple Mapping this is no longer an issue and important mechanistic data is revealed by 
ensuring dense scar collection. 
 
Attention should be made to ensure structures such as valve annuli and pulmonary vein 
ostia are mapped adequately and once the map has been collected, the valve annuli should 
be cut out. 
 
2.3.2.1.1 Map Setup and Map Collection: Fast Anatomical Maps in Stable mode are selected 
on the Map Setup screen.  Do not opt to “apply the FAM to collected points” in order to 
create a smooth contoured shell.  Having “Initialized”, limit the mapping resolution to 10 to 

 
ensure a smooth surface.  The map is collected as a bipolar voltage map.  “Scar auto 
tagging” is turned off, in order to map the entire chamber evenly throughout, and 
importantly this includes all scar.  Set the fill and colour threshold to 5mm to see areas 
without point acquisition and to help fill in all the areas.  Collect at least 250 points, ensuring 
>25 points around anatomical structures e.g. valve annulus, pulmonary veins so the 
activation direction can be clearly seen.  Annular signals are tagged separately on the map 
and the valve annulus is removed.   
 
2.3.2.1.2 ConfiDENSE: An alternative to point-by-point collection is the use of the CARTO3 
v4 ConfiDENSE Continuous Map Acquisition function. High point density acquisition 
improves RM interpretation and we have been able to collect substantially higher number 
of points (>2000 points in approximately 15 minutes with a LASSO NAV) using this facility. A 
series of point filters are available as shown in the image below; 
  
The following are optimal for Ripple mapping; 
 
Cycle Length (CL) Range: ±5% of the TCL 
A point will only be collected if the cycle length is within this defined range. This 
avoids ectopic beats and major cycle length variation causing problems in 
interpretation. Such points are easily seen as rogue points in a Ripple Map but 
obviously it would be better not to collect these in first place. 
 
Position Stability: 2mm (range is 0-12mm) 
Ensuring the catheter is stable before collecting the point is considered to reduce 
noise signal from catheter movement. 
 
Density: 3mm (range is 1-4mm)  
A 3mm inter-point distance is the ideal balance between a dense map and one 
that results in overcrowding of Ripple bars. 
 
LAT stability: switched OFF.   
As Ripple Mapping is not dependent on LAT annotation, application of this filter may 
slow down map acquisition collection. This is an important function when using an 
activation map with Continuous Acquisition but not necessary for Ripple Mapping.  
 
2.3.2.1.3 Which chamber to map first?  If coronary sinus activation is “proximal to distal” 
and isthmus dependent right atrial flutter cannot be excluded on 12 lead ECG, in order to 
avoid tachycardia change or termination with entrainment, a right atrial map should be 
collected first.   
 

 
2.3.2.2 The CARTO Ripple Map user interface 
There are three toolboxes relating to Ripple Mapping in the CARTO 3 v4 User Interface.  
These are called “Ripple Map Preferences”, the “Ripple Cine Player”, and the “Ripple 
Viewer” and are described in detail below. 
 
2.3.2.2.1 Ripple Map Preferences (Tools > Ripple Map Preferences): This provides a series 
of options that determines the voltage at which bars are visible and the voltage-height 
relationship.   
  
‘Show bars above’ dialog box is used to enter the minimum voltage at which the Ripple bars 
become visible. As every deflection within the electrogram is shown by the moving bar on 
the map, it is helpful to remove noise from the signal. ‘0.03mV’ (default) is a reasonable 
setting to eliminate noise artefact for SmartTouch catheters and ‘0.07mV’ for LassoNav 
catheters.  Obviously, for every Lab this may be different and it is important to reduce noise 
as much as possible and have this setting as low as possible. This will enable the lowest 
amplitude signal to be seen on the Ripple Map. 
 
‘Size factor’ collectively magnifies or reduces the height of the bars.  Options include x1, x2, 
x4, x8.  The default setting is X8. 
 
‘Clip bars above’ option will limit the height of the bar at the level which represents that 
voltage. For example, if bars are clipped above 0.5mV and the electrogram reaches 5mV at 
its peak deflection, then it will remain at the height attained for 0.5mV until the voltage falls 
below this level.  If the bars are too small, it can limit visualisation of the Ripple wavefront.  
However, if the bars are too tall, they can overcrowd the atrial geometry and overlap each 
other again making interpretation difficult.  In most cases, the isthmuses of interest will 
have low amplitude signal and may lie within or near regions of scar, so the bars will be set 
up to optimise for these low amplitude signals with bars shown above 0.03mV and clipped 
at 0.25mV with Size set to High. The User can adjust these three parameters to maximise 
the effectiveness of visualisation in other situations. 
 
‘Show markers’ option on the “Ripple Map Preferences” screen does not relate to the bar 
height settings.  Selecting this option allows “Ripple Markings” to be visualised on the map.  
“Ripple Markings” are discussed in detail below (see Ripple Viewer section). 
 
2.3.2.2.2 Ripple Cine Player (Map>Ripple Map>Play): This is used to view the Ripple Map. 
The playback speed can be selected by the operator and options are: x1, X2 , X3, x4, x5.  
Default is x4.   
  
When played, the Ripple Map automatically runs in a continuous loop.  Playing the map 
using the default settings  enables a rapid appreciation of the global activation pattern.  At 

 
areas of interest, the playback speed can be reduced to study local electrograms and 
patterns of activation.  Of note, the map can be played frame by frame, including in reverse, 
which is particularly useful when trying to find the earliest bar during focal activation. 
 
2.3.2.2.3 Ripple Viewer (Window > Ripple Viewer): This function allows the user to define 
the duration of the ‘time-window’ viewed as a Ripple map. It also enables the operator to 
review a series of electrogram signals from an area of interest with marked points (mouse 
right click > Ripple Markings) side by side.  This can be used to observe local activation 
sequences along potential conduction channels or electrogram morphology.  For example, it 
is particularly useful to determine if the complete cycle length has been mapped in a circuit 
or which limb of a dual-loop circuit enters the common isthmus first.  These “Ripple 
markings” can be hidden from the map by unselecting the “show markers” option on the 
Ripple “Map Preferences” panel 
 
2.3.2.3 Analysing a Ripple Map 
A Ripple Map will show more information than current mapping systems and it is helpful to 
go through a set approach to familiarise the operator. 
 
2.3.2.3.1 Set up Ripple Viewer to display multiples of full tachycardia cycle length: The 
Ripple Viewer is used to define the duration of the ‘time-window’ presented as a Ripple 
map.  When first displayed, the timings are automatically set to the LAT Window of Interest 
around the reference signal (red dotted line) as defined by the operator at the beginning of 
the case.  Lead II body surface channel is always displayed in the viewer.  Displaying two 
complete cycle lengths of the tachycardia in the Ripple Viewer guarantees the whole circuit 
is viewed without interruption.  The Ripple Viewer calipers can be manually set to display 2 
full tachycardia cycle lengths. 
  
2.3.2.3.2 Set up Ripple Preferences and Ripple Cine Player: Once the Ripple Map is playing, 
the user will be able to identify wavefronts moving around the chamber. In cases of focal 
tachycardia the mechanism may be obvious at this stage.  
 
2.3.2.3.3 Dynamic Scar Thresholding: Ripple Map displays both voltage and activation 
information on the same map.  Dynamic scar thresholding is a process of altering the scar 
bipolar voltage settings to display only areas dense scar without a propagating wavefront.  
As there is no nominal scar setting for atrial voltage maps, an arbitrary high empirical scar 
setting should be applied. As scar settings are reduced, potential isthmuses of conduction 
may be seen, bounded by either areas of scar, anatomical boundaries (veins, valve annuli) or 
previous ablation lines.  A narrow window between the upper and lower voltage (eg. 1mV-
1mV) is applied as this presents a clear distinction between areas depicted as healthy 
(purple) and scar (red).  With a large difference (eg 1mV-0.8mV) additional colors are seen 
on the voltage map (yellows, greens, blues etc) which can be a distraction.  Maps should be 

 
collected as a bipolar voltage map using empirical scar setting of 1mV-1mV.  Having 
appreciated global activation, the scar settings should be reduced in a stepwise fashion (e.g. 
0.5mV-0.5mV, 0.4mV-0.4mV, 0.3mV-0.3mV, 0.2mV-0.2mV, 0.1mV-0.1mV) until only areas 
marked as scar (red in color) are those that lack clear Ripple wavefront propagation.  This 
has often highlighted islands of scar bordering isthmuses of conducting tissue. 
 
2.3.2.3.4 Review Chamber in multiple orientations. The first moment the Ripple map is 
played, in particular with very high point density (>1000 points), there can be so much 
information displayed on the map that a systematic approach is helpful.  First begin by 
localising an obvious area of Ripple wavefront on the map.  Next, rather than following the 
wavefront in the direction of activation, rotate the map in the opposite direction.  
Progressively following the wavefront in reverse can be a useful way of tracking the origin of 
activation in a focal tachycardia or completely around the map in a macroreentrant circuit. 
At areas of interest, the playback speed can be reduced (60fps or 20fps) to study local 
electrograms and patterns of activation.  
 
If a focal tachycardia is suspected, the times frame in the Ripple Viewer can be shortened to 
remove electrical inactivity in order address the area of electrical breakout.  The map can be 
played frame by frame using the Step forward/back icon in order to identify the earliest 
Ripple Bar representing the focal origin. In most cases focal tachycardias are relatively easy 
to identify so long as activation is seen to travel in all directions from the source. If the 
source is at an anatomical edge such as the annulus or the scar then the operator needs to 
be aware that if the anatomical boundary or scar has not been fully mapped then errors can 
occur. 
 
Macroreentrant circuits can be more complicated. The left anterior oblique view with the 
valve en-face should be used to exclude peri-annular dependent circuits, and right lateral 
view to check for roof dependency.  Following this each view is reviewed to understand 
further aspects of the circuit.  
 
2.3.2.3.5 Use of design lines:  In some cases where there are multiple areas of ablation and 
idiopathic scar, circuits can be complicated and placing a design line can be a useful visual 
aid.  
 
2.3.2.3.5 Importing old studies:  CARTO3 v4 allows maps from previous studies (Study > 
Load Maps from Previous Study) to be imported into the current study and viewed 
simultaneously, live, adjacent to the active map.  This allows the operator to view the 
location of previous ablation lines.  In more complex circuitry, this may prove helpful in 
trying to fathom some of the more complex wavefront patterns which might take some 
unexpected bend or stop abruptly around areas of iatrogenic conduction block. 
 

 
2.3.2.4 Avoiding errors with a Ripple Map 
A single entrainment after making a diagnosis with the Ripple Map can be reassuring in complex 
circuits. In complex cases, the potential for dual loop re-entry is relatively common. In these 
situations ablation of the clinical tachycardia may cause a small change in cycle length when 
transitioning to the bystander circuit.  Unless a multi-electrode catheter, such as a coronary sinus 
decapole, shows a change in activation pattern, the transition may not be appreciated.  Therefore, 
periodic checking of the cycle length is recommended and if the tachycardia has not terminated 
after an appropriate number of lesions delivered, a localised re-map with dense acquisition around 
the region of interest using RM can determine whether the tachycardia has changed.   
Finally, if the. bars are moving out of sequence around the chamber randomly, check the cycle 
length and fiducial reference for changes as the map is unlikely to be interpretable. 
 
 
2.3.4 GROUP 2 (CARTO ISOCHRONAL ACTIVATION MAP) 
 
This will be according to standard practice of the operator. Entrainment can be used to 
guide the appropriate chamber to map.  Points are collected using ConfiDENSE continuous 
mapping and auto-annotation unless the operator deems otherwise.  Further manual 
annotation can be performed as appropriate.  When the operator is satisfied adequate 
number of points have been collected, the time and number of point is noted and a 
diagnosis is made.  
 
 
2.3.5 Categorisation of maps 
 
Grade I map -  
High diagnostic confidence with clear patterns of activation evident; 
and operator selects optimal ablation site from the map. 
 
Grade II map -  
Moderate diagnostic confidence with some regions where activation 
is not clearly seen; a single entrainment site requested before first 
ablation 
 
Grade III map - 
Low diagnostic confidence and alternative arm (Ripple/Conventional 
activation) or multiple entrainment requested before first ablation 
 
Grade IV map -  
Non-diagnostic despite all attempts. 
 
Uncategorised -  
AT terminated or changed during point collection/pacing 
 
 
 
3 STUDY OUTCOME MEASURES 

 
 
PRIMARY ENDPOINT  
1) Tachycardia change/termination with first ablation set after map 
categorisation . 
SECONDARY ENDPOINT 
1) Tachycardia change/termination during point collection 
2) Tachycardia change/termination during pacing manuoevre 
 
 
 
 
3) Failure to ablate/ change tachycardia with ablation.   
 
 
 
 
 
 
 
 
4) The need for entrainment mapping. 
 
If tachycardia does not change with the proposed ablation lesion, or changes to another 
tachycardia, then operators can continue mapping and performing ablation in the patient’s 
best interests. 
 
If the tachycardia changes prior to the first ablation set, or in the event of a grade 3 
diagnosis, operators can continue proceed as per individual preference. 
 
3.1 Post ablation map in patients with any linear lesion sets:  
The method for confirming block along a linear lesion line is according to operator 
preference 
 
3.2 FOLLOW UP 
As we are only studying the acute end point of tachycardia termination, no long term follow 
up data is required.  Patients will be followed up as is routine in their Electrophysiology 
clinic outside of the research protocol.  Any redo procedures over the subsequent year 
should be reported to the trial management team.   
 
4.  DATA ANALYSIS 
The following data will be assessed:  
 
Mapping: 
1. Number of points  
 
Tachycardia: 
1.The diagnosis is recorded as either focal (localized reentry) or macro-reentry 
2. The grade of diagnostic confidence is recorded 
3. Validation of the diagnosis with change of activation/termination with ablation. 
4. Number of times entrainment performed 
 
Ablation: 
1. Location of ablation delivery 
2. The duration of RF before tachycardia change/termination 
 

 
5. PARTICIPANT ENTRY  
 
5.1 PRE-REGISTRATION EVALUATIONS  
The direct care team will identify potential study patients against inclusion and exclusion 
criteria, before the Investigator determines their eligibility for participation.  The 
Investigator will discuss the rationale for the study, study procedures, risks and benefits and 
all other issues mandated by the consent process. The potential participant will be offered 
an opportunity to participate in the study and written informed consent will be obtained if 
they agree. Study procedures and assessments will only be performed after written 
informed consent has been obtained.  Patients recruited to this study will not need to 
undergo any additional investigations above what is required for a standard AT ablation 
procedure.  The informed consent process and all study assessments will be documented in 
the patient’s medical notes and study case report forms.  
 
5.2 INCLUSION CRITERIA 
To be eligible for the trial, subjects must meet all of the following criteria: 
1) Patients undergoing ablation of sustained atrial tachycardia (post AF ablation) using 3D 
mapping. 
2) Age range 18-85yrs. 
3) Signed informed consent 
 
5.3 EXCLUSION CRITERIA  
Subjects with any of the following will be excluded from the study: 
1. Patients with typical flutter.  
2. Patient with non-sustained atrial tachycardia 
3. Contraindication to catheter ablation 
4. Unable to give informed consent 
 
5.4 WITHDRAWAL CRITERIA 
If patients lose the capacity to consent or wish to withdraw voluntarily, then they will be 
excluded from the study from this point. If the patient has agreed on the consent form, any 
data collected up to this point will be included in the data analysis.   
 
 
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 will be reported. Depending on the nature of the event the reporting 
procedures below will be followed. As the patients are undergoing clinically indicated 
procedures any questions concerning adverse event reporting will be directed to the main 
clinical departmental lead and clinician supervising the case in the first instance.  
6.2.1 Non serious AEs  
All such events, whether expected or not, will be recorded.  
6.2.2 Serious AEs  
A SAE form should be completed and faxed to the Chief Investigator within 24 hours. 
However, relapse and death due to non-cardiac conditions, and 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> where in the opinion of the Chief 
Investigator, the event was:  
 ‘related’, ie resulted from the administration of any of the research procedures; and  
 ‘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 SAEs.  
Local investigators should report any SAEs as required by their Local Research Ethics 
Committee, Sponsor and/or Research & Development Office.  
 
7. STATISTICS 
 
Sample Size: 

 
 
 
Our retrospective study demonstrated a diagnostic yield using RM compared to standard 
CARTO activation maps of 80% vs 50% (Jamil-Copley et al. 2013).  Assuming the same 
outcome measures, this study is designed to be sufficiently large to detect a difference 
between arms with 80% power, at the 5% two-tailed significance level.  This requires a 36 
patients in each group to give a minimum sample size of 72 patients.  We have elected to 
recruit a total of 100 patients into the study. 
 
Categorical variables will be expressed as percentages. Continuous variables will be 
expressed as mean ± 1 standard deviation for parametric data and/or median ± interquartile 
range for non-parametric data.  The 2 groups will be compared using a student’s t-test for 
parametric data and Mann-Whitney U-Test for non-parametric data. A value of p<0.05 will 
be considered significant. 
 
 
8. DATA MANAGEMENT AND QUALITY CONTROL 
The complete dataset will be collected for all patients who are randomised into the trial.  
The signed, original informed consent forms and the documentation of all study procedures 
and assessments will be kept in the patients’ study notes. All data will be transferred to the 
study co-ordination centre with all appropriate supporting documentation as required such 
as hospital reports or imaging reports with all patient identifiers removed. Patients study 
documents will be identified by their study-specific patient number allocated at 
randomisation.   
 
 
9. REGULATORY ISSUES  
 
9.1 ETHICS APPROVAL  
Ethical approval for this study was granted by the NRES Committee London – Fulham on the 
3rd December 2014. 
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. The study must be submitted for Site Specific Assessment 
(SSA) at each participating NHS Trust.  The Chief Investigator will require a copy of the Trust 
R&D approval letter before accepting participants into the study.  Ethics and R&D approval 

 
letter will be required by the Study Co-ordination Centre before accepting participants into 
the study.   
 
9.2 CONSENT  
Consent to enter the study will 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 will be obtained. The right of the participant to refuse to participate 
without giving reasons will 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 will 
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.  
 
9.4 INDEMNITY  
Imperial College Healthcare NHS Trust holds standard NHS Hospital Indemnity and 
insurance cover with NHS Litigation Authority for NHS Trusts in England, which apply 
to this study.  
 
9.5 SPONSOR  
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.