PeAF-Box. A Study to Investigate the Feasibility, Safety and Efficacy of Isolating the Left Atrial Posterior Wall Adjunctive to Pulmonary Vein Isolation as First-line Therapeutical Strategy in Treatment of Persistent Atrial Fibrillation
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: René Husted Worck

René Worck, MD, Ph.D.  Copenhagen November 2015  
PeAF box feasibility ver 2.3 
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PeAF-BOX feasibility 
 
Principal Investigator René Worck MD, PhD 
 
- EP team department of Cardiology  
- Gastroenterological endoscopy unit 
 
Gentofte-Herlev Hospital 
University of Copenhagen, Denmark 
 

René Worck, MD, Ph.D.  Copenhagen November 2015  
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List of Abbreviations: 
AAD 
 
Anti Arrhythmic Drugs 
AE 
 
Adverse events 
AF 
 
Atrial fibrillation 
Afl 
 
Atrial flutter 
AT 
 
Atrial Tachycardia 
CF 
 
Contact Force 
CFAE 
 
Complex Fractionated Atrial Electrograms 
CTIB 
 
Cavo Tricuspidal Isthmus Block 
Echo 
 
Echocardiogram 
EP Lab 
 
Electrophysiology laboratory 
FTI 
 
Force-Time- integral 
LA 
 
Left Atrium 
LAPW 
 
Left Atrial Posterior Wall 
LAPWI 
 
Left Atrial Posterior Wall Isolation 
MIB 
 
Mitral isthmus Block 
PAF 
 
Paroxystic Atrial Fibrillation 
PeAF 
 
Persistent Atrial Fibrillation 
PV 
 
Pulmonary Vein 
PVI 
 
Pulmonary vein isolation 
QOL 
 
Quality of life 
RA 
 
Right Atrium 
SR 
 
Sinus Rhythm 
WACA 
 
Wide Area Circumferential Ablation 
 
 
 
 
 
 
 
 
 

René Worck, MD, Ph.D.  Copenhagen November 2015  
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Content 
List of Abbreviations ......................................................................................................................................... 2 
1 Background..................................................................................................................................................... 4 
1.1 Defining the Problem .............................................................................................................................. 4 
1.2 Demand and Opportunities ...................................................................................................................... 5 
2 Studies addressing adjunctive linear lesions in LA in PeAF .......................................................................... 6 
2.1 Published studies ..................................................................................................................................... 6 
2.2 Ongoing Studies (source: www.clinicaltrials.org) ................................................................................... 9 
2.3 Current status and ideas for further research ........................................................................................... 9 
3.1. Proposal of study ...................................................................................................................................... 12 
3.2 Primary aims .......................................................................................................................................... 12 
3.4 Hypothesis ............................................................................................................................................. 13 
3.5 Flow sheet .............................................................................................................................................. 13 
3.6 Methods ................................................................................................................................................. 13 
3.6.1 Inclusion criteria: ............................................................................................................................ 13 
3.6.2 Exclusion criteria: ........................................................................................................................... 13 
3.6.3 Data handling .................................................................................................................................. 13 
3.7 Statistical Considerations ...................................................................................................................... 14 
3.8  Risks, inconvenience and patient exposure to adverse events .............................................................. 15 
3.9 Research ethical considerations ............................................................................................................. 16 
3.10 Patient recruitment and informed consent ........................................................................................... 17 
3.11 Proposed substudies  ............................................................................................................................ 17 
3.11.1 ECG study .................................................................................................................................... 17 
3.11.2 ECHO study .................................................................................................................................. 17 
3.11.3 Viability of posterior wall ............................................................................................................. 17 
3.11.4 Types of recurrence ...................................................................................................................... 17 
3.11.5 Gap localization at 3 month per protocol re-evaluation ............................................................... 17 
3.11.6 Biochemical markers .................................................................................................................... 18 
3.12 Budget ................................................................................................................................................. 18 
3.13 Economy and sponsorship ................................................................................................................... 18 
3.14 Publication policy ................................................................................................................................ 19 
Reference List .................................................................................................................................................. 20 
Appendix A.  PeAF-BOX - feasibility.  Flow-sheet ........................................................................................ 23 
Appendix B.  PeAF-BOX – feasibility - Procedure details ............................................................................. 24 

René Worck, MD, Ph.D.  Copenhagen November 2015  
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PeAF-BOX Feasibility 
 
A Study to Clarify the Safety and Feasibility of Isolating the Left Atrial Posterior Wall Ad-
junctive to Pulmonary Vein Isolation - the "Box Lesion" as First-line Therapy in Ablation for 
Persistent Atrial Fibrillation using SF-Smarttouch ® technology. 
1 Background  
1.1 Defining the Problem  
   Favorable outcomes in terms of quality of life, decreased symptom burden and freedom from atri-
al fibrillation (AF) are well established in patients with paroxysmal AF (PAF) who undergo pulmo-
nary vein isolation (PVI). In more than 90 % of these patients electrical triggers and/or the electrical 
interplay between the left atrial body (LA) and the pulmonary veins are paramount for the initiation 
and maintenance of atrial fibrillation. Therefore efficient and durable PVI - when achieved - cures 
PAF in most patients. 
   Clinical experience and scientific studies however also agree that outcomes after PVI in patients 
with persistent atrial fibrillation (PeAF) are less favorable 1 and PVI in these patients carries a much 
higher rate of recurrent AF related arrhythmias. This lower success rate has been attributed to the 
assumption that atria that persist fibrillating for prolonged time periods harbor more complex ana-
tomical and physiological disease with myofibrillar remodeling and disarray, increased wall strain, 
fibrosis etc. This translates into a complex and insufficiently understood electrophysiological be-
havior of the atrial wall - e.g. extrapulmonary triggers and rotors2, 3.  
   The relatively poor outcome after PVI alone in PeAF in comparison to PAF has been interpreted 
as owing to a shift in the relative pathophysiological importance of pulmonary vein triggers versus 
the above mentioned complex behavior of the LA - the "substrate" to maintain atrial fibrillation. 
Accordingly different approaches and concepts have been developed to modify or eradicate the ex-
trapulmonary arrhythmogenic atrial substrate as an adjunct to pulmonary vein isolation. Different 
techniques include supplementary lines in both the left and the right atrium (RA), mapping and ab-
lating presumptive rotating electrical wave fronts (rotors), targeting the ganglionic plexi in close 
proximity to the LA posterior wall 4 as well as specific targeting of complex fractionated electro-
grams (CFAE). In a comprehensive meta-analysis of available data on the relative efficacy of dif-
ferent ablation strategies in PeAF Wynn and coworkers recently found that there are no data availa-
ble which clearly point to the best first-line ablation strategy in patients with PeAF 5. Their findings 
concur with another recent Cochrane analysis 6 which concluded, first that PVI remains the well 
documented baseline treatment, and second that supplementary lesions in the left atrium may in-
crease the success rate in PeAF - however there is no scientific evidence to support one adjunctive 
ablation strategy added to PVI (e.g. PVI + roof line; PVI + CFAE ablations ; PVI + mitral isthmus 
line etc.) over the other. Current status is that ablating a limited number of supplementary lines in 
the left atrium is beneficial in PeAF. Which lesion set is better however still remains unsettled.  

René Worck, MD, Ph.D.  Copenhagen November 2015  
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1.2 Demand and Opportunities 
   Due to the demographic development the population of patients with atrial fibrillation – both PAF 
and PeAF is expected to increase substantially over the next decades 7 and so is the need and ex-
pected demand for a safe evidence-based interventional treatment. In the area of AF ablation at least 
two important steps forward have been taken over the last couple of years: First Technological de-
velopment such as reliable force sensing capabilities in the ablation catheters, precision and reliabil-
ity of electro-anatomic mapping systems etc. Second, due to increased ablation activity the operator 
experience combined with optimization over time of the entire EP-lab workflow such as efficient 
and safe perioperative antithrombotic treatment have increased markedly.  
   Based on these developments ablation for PAF has become a relatively fast and safe procedure. 
PVI using wide area circumferential ablation (WACA) to obtain durable bidirectional block of elec-
trical conduction between the pulmonary veins and the LA body is thus routinely achieved in most 
electrophysiology labs in Denmark. Success rates in terms of freedom from recurrence of symptoms 
or signs of AF, atrial tachycardia (AT) or atrial flutter (Afl) is - depending on the quality and quan-
tity of post-procedure follow-up (FU) - currently perceived to be in the range of 60-70 % 1 one year 
after one ablation for PAF with some late recurrences over the following years.  
   However, after one ablation for PeAF the one-year arrhythmia free rate is probably 30% 1, 8 alt-
hough recent studies may point to arrhythmia free rates closer to 50 %. It must however be stressed 
that available data are heterogeneous and dependent on the follow-up scheme and the characteristics 
of the studied patient cohorts. For instance the duration of PeAF, the size of the LA, the presence of 
mitral valve disease, heart failure or other comorbidities contribute to the complexity of the single 
AF case and thus inversely to success rates after PVI. 
   It is widely accepted that success rates after PVI alone in PeAF are unsatisfactory. Until present 
time only relatively weak evidence point to positive effects of intervening with the electrical proper-
ties of the LA posterior wall (LAPW) by ablating one or two (thus isolating the LAPW) lines an-
chored to the isolated PVs.  
Putative effects of "add on" LAPW isolation (LAPWI) may include:  
1) The basic goal of isolating the pulmonary veins from the remaining LA is fortified at the posteri-
or aspect where the box lesion will serve as a "second line of defense". 
2) Posterior wall ablation may “inadvertently” damage or modify potentially pathophysiological 
important ganglionic plexi situated in close proximity to LAPW 9, 10. 
3) Posterior wall fibrotic and potentially arrhythmogenic areas 11 will be isolated from the remain-
ing LA 
4) Macro reentry tachycardias involving LAPW are hampered – given the lines remain intact. 
5) Insufficient lines with gaps/slow conduction predispose to atrial flutters.  

René Worck, MD, Ph.D.  Copenhagen November 2015  
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   Thus: Effective LAPW-isolation added to PVI might carry significant benefits as first-line treat-
ment in PeAF while in-effective LAPW isolation may worsen procedural outcomes. We therefore 
examined the currently available literature and ongoing studies which more or less directly address 
the putative antiarrhythmic effects of electrical isolation of LAPW. The findings are presented be-
low. 
2 Studies addressing adjunctive linear lesions in LA in PeAF. 
2.1 Published studies 
1993 Cox et al 12 published their 5 year outcomes in 65 patients (~50 % PeAF) whom they were 
able to follow up after the original surgical MAZE procedure which included several "cut and sew" 
lesions in both atria in order to conduct the sinus node impulse through a maze to the AV node. The 
core lesion in the LA was isolating the LAPW "en bloc" with the PVs although the concept of "PV 
triggers" was not known at that time. The procedure had a very high success rate but several serious 
complications including the need for permanent pacing and death.  
First generation ablation technology (solid tip)  
2003 Ernst et al. 13 studied the feasibility and effect of different lesion sets in the LA in 84 patients 
on freedom from AF. Electroanatomic mapping (EAM) using Carto® and solid-tip (non-cooled) 
ablation catheters were used. The different lesion sets were intended to combine PVI with other 
lesions and were often impossible to achieve as was the ability to achieve and maintain electrical 
conduction block with the technology used. One of the designs, the "A" type lesion set attempted to 
mimic the "core" line of the surgical Cox procedure. This design consist of one long continuous 
encircling line that isolates the paired PV ostia together with the posterior LA wall from the rest of 
the LA. In only one (of 20) patients this design led to complete (isolating) lines. This one patient 
was arrhythmia free at 3-years F-U. All other patients experienced early recurrences. The remaining 
lesion sets were all equally difficult to complete and inefficient. In retrospect the technology of 
those days was not sufficient to obtain durable isolating lines in the LA. 
2004 Kottkamp et al. 14 followed patients one year after attempted WACA + roof line + mitral 
isthmus line in 100 AF patients (20 % with PeAF). They used solid tip ablation catheters and did 
not measure if PVI or electric conduction block of lines were achieved. At one year F-U 65 % of the 
PeAF pts - some on AAD had recurrence on 7 day ECG monitoring. 
 
Second generation ablation technology (cooled tip)  
2005 Fassini et al. 15 randomized 61 patients with PeAF to PVI with or without additional mitral 
isthmus block (PVI + MIB). At 18 months (50 % still on AAD) F-U only 36% in the PVI only 
group were recurrence free while 74% in the PVI + MI group were recurrence free. 
2006 Willems et al. 16 randomized 62 patients with PeAF to PVI + CTI block or PVI + CTI block + 
roof line + MIB. They found that it was difficult to achieve electrical conduction block of both roof 

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line and mitral isthmus line. At long term F-U (70 weeks) only 20 % in the PVI + CTI group were 
in SR while 69 % of the patients with additional lines in the LA were in SR  
2007 Sanders et al. 17 reported their results in 27 patients with "chronic" AF. Patients had a median 
continuous AF duration of 24 months at the time of the procedure and the atria were moderate- 
severely enlarged (AP diameter ~ 49 mm). Procedures started with patients in AF. First PVI, then 
CTI block and then LAPWI were performed. In five patients (19%) the AF terminated during 
LAPWI – either to SR or Afl. The patients had clinical follow up every three months for one year. 
Further F-U was outside protocol. 50 % of the patients developed atrial arrhythmias at an average of 
10 months after the index procedure. Four of these patients were successfully re-ablated to SR off 
AAD while 1 patient achieved SR on AAD without further ablation. Using this strategy they 
achieved a 68% SR success rate at two years F-U. 
2008 Gaita el al. 18 randomized 79 patients with PeAF in a 1:2 fashion to either PVI + CTI block 
(26 pts.) or PVI + Lines in LA + CTI block (53 pts.). Electrical conduction block to the pulmonary 
veins (PVI) was not formally tested and the persistence of the electrically blocking lines in the LA 
(roof line and mitral isthmus line) were not formally tested either. F-U continued for at least 3 years 
with 24 h Holter monitoring at intervals. At one year F-U after one procedure 27% of the PVI alone 
patients and 45 % in the PVI + lines experienced freedom from arrhythmia. After 3 years and 
additional ablations, if needed, 39 % and 75 % were free from AF. 
2009 Tamborero et al. 19 studied 120 consecutive patients with AF (40% with PeAF) who under-
went "baseline ablation" with PVI + MIB and randomized them to either additional roof line or roof 
line and inferior line that is: LAPW isolation. They used a single transseptal technique (no "lasso" 
catheter) and did not rigorously prove uni- or bidirectional PVI or electrical conduction block over 
the ablation lines. However in some of the patients offered LAPW isolation they demonstrated dis-
appearance of signals in the LAPW box. At 10 months F-U the overall recurrence rate was 55% in 
both groups. No data were given pertaining to PeAF patients alone.  
2010  Mikhaylov et al. 20 Randomized 34 patients with longstanding PeAF to either a "baseline" 
lesion set consisting of  PVI + roof line + MIB vs. "baseline" + septal line in LA anchored between 
the right superior pulmonary vein and the mitral annulus. PVI with electrical conduction block was 
shown using the lasso technique but conduction block over the other lines was not rigorously tested. 
At two year follow-up after one ablation the recurrence rate on AAD (Amiodarone or D-sotalol) 
was 60 % in both groups. 
2011 Pak et al. 21 Investigated 200 patients with PeAF who in a non-randomized fashion were of-
fered either PVI + roof line + MIB or PVI + roof + left atrial anterior wall line (LAAW). PVI and 
conduction block over the roof line were documented by pacing maneuvers in all patients. Ablation 
line conduction block was provable by differential pacing in 69% in the LAAW group whereas line 
durability was only shown in 32 % in the LLMI group. The one year AF free survival on AAD was 
73% in the LAAW group compared to 63 % in the LLMI group. 

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2011 Estner et al. 22 randomized 116 patients with PeAF to either PVI using WACA and addition of 
at least one but up to all three of the following lines: LA roof, LA anterior (RSPV to mitral valve) 
or CTI line in the right atrium (group 1) or ostial single vein PVI using spot lesions + elimination of 
all CFAE potentials in both atria (group 2). Cooled tip ablation. At one year F-U freedom from 
atrial tachyarrhythmia was 37 % in group 1 and 39% in group 2 after one single procedure. 
2011 Chilukuri et al. 23 randomized 29 consecutive patients with AF (7 with PeAF) to either PVI or 
a "BOX" ablation much like Cox´ original surgical "core line". They documented unidirectional 
electrical conduction block to the LAPW (but not the PVs per se) in the "BOX" group and the PVs 
in the PVI group. Follow-up was based on a portable leadless Omron® monitor with patients in-
structed to record 30 sec/day and during symptomatic episodes. At 10 months follow up the recur-
rence free survival was 25% in the "BOX" group and 15 % in the PVI group (P = 0,52). These were 
fairly poor results in both groups. Larger sample sizes, rigorous testing and documenting electrical 
conduction block over lines might have proven interesting. 
2012 Lim et al. 24 randomized 220 AF patients (38% with PeAF) to receive either single ring abla-
tion which attempts to isolate the pulmonary veins and LAPW in one continuous ring ablation (SRI) 
similar to the Cox core line OR a very wide WACA connected with a roof line (WAI). Both these 
groups were further randomized to MIB or not (2x2 factorial design). Most of the patients in all 
groups also had a CTI ablation. At two-year follow-up among the PeAF patients the AF free surviv-
al was 68 % in the SRI and 53 % in the WAI group (NS). Data on AF related (AF + Afl + AT) re-
currence was not given for PeAF but overall was around 50% at 2 year follow-up. Attempted MIB 
was only successful in 54% of the patients randomized to that treatment. Sample size was obviously 
too small for comparison within the PeAF group. 
 2014 Saad and Slater 25 published a non-randomized series of 25 patients with both short- and 
longstanding PeAF lasting on average 11 months. At the initial procedure all patients had PVI + 
LAPWI + CTIB. Further, dormant conduction was induced with adenosine and ablated. AAD were 
continued for one month and ambulatory F-U was conducted at 1, 3, 6 and 12 months and 7 day 
Holter monitors were done when appropriate. On average F-U at 16 months 20 pts. (80%) were free 
from arrhythmia (two of these in AADs).  
2014 Very recently Kim et al. 26 randomized 120 patients to PVI + several lines in the LA and RA 
(control) or the same lesion set as control + a lower posterior line thus leading to LAPW isolation. 
At 12 months F-U the AF recurrence rate was significantly lower in the LAPW group (17%) com-
pared to control (37%).  
 
Cool tip technology comparing "lines" and CFAE ablation 
Dixit et al 27 randomized 156 patients with PeAF to 3 arms: 1. PVI + ablation of non-PV triggers 
identified using a stimulation protocol (standard approach); 2. Standard approach + empirical abla-
tion at common non-PV AF trigger sites (mitral annulus, fossa ovalis, Eustachian ridge, crista ter-

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minalis, and superior vena cava); or 3. Standard approach + ablation at sites of left atrial CFAE´s. 
At one year follow up after one procedure on AAD´s 49%, 58% and 29% of patients were free of 
atrial arrhythmias in arms 1, 2 and 3 respectively.  
In the STAR AF II trial28 a total of 549 PeAF patients were randomized in a 1:4:4 fashion in an in-
ternational trial spanning four continents and 35 ablation centers to PVI, PVI + CFAE or PVI + 
Lines (roof + MIB). Surprisingly in the PVI only group freedom from AF and any AF related tach-
ycardia after one procedure was 59 % (!) and 49 % respectively at 18 months follow-up. Another 
important finding was that in the "lines" group electrical block was only achieved in 74% of pa-
tients. Compared to PVI alone the outcomes at 18 months F-U tended to worsen in the PVI + lines 
and the PVI + CFAE groups (Freedom from AF 44% and 37 % respectively) !  
Taken together these recent studies speak against the use of CFAE ablations and the proposed sup-
plementary lesion sets in patients with PEAF.  
2.2 Ongoing Studies (source: www.clinicaltrials.org) 
A) Outcome of atrial fibrillation ablation after permanent pulmonary vein antrum isolation with or 
without proven left atrial posterior wall isolation. 29 
   A study initiated in August 2012 as collaboration between Texas Cardiac Arrhythmia Research 
Foundation, a center in Milan and two centers in China: Beijing and Wuhan. They started recruiting 
patients in 2013 for the study which randomizes patients with Atrial fibrillation PAF and "non-
PAF" (short term and long term persistent) to either WACA or WACA + proven isolation of the left 
atrium posterior wall (LAPW). Recruitment appears to be multi-center. The technique of isolating 
the LAPW and schedule F-U is not depicted. A repeat procedure to prove and ensure, by further 
ablation if necessary, PVI and LAPW isolation will be mandatory three months after the index pro-
cedure. Estimated primary completion date was august 2014 and estimated publication is 2016. An 
estimated 400 patients will be recruited. 
B) Substrate Ablation and Remodeling in Non-paroxysmal Atrial Fibrillation (SMAAN-PAF) 30 
   A study sponsored by The Liverpool Heart and Chest Hospital NHS foundation Trust. In a single 
center design 130 patients with “non-paroxysmal” atrial fibrillation are randomized and treated sin-
gle blinded with PVI + amiodarone vs. PVI + amiodarone + additional lines (LA roof + mitral isth-
mus + CTI) Enrollment started  2011 and has stopped recruiting patients. Primary outcome measure 
is freedom from atrial fibrillation/ atrial tachycardia at 6 months following a single procedure.  
2.3 Current status and ideas for further research 
Status on linear lesions in PeAF 
   As discussed there is presently no known "best practice" of supplementary lesions added to PVI in 
PeAF. Several studies were hampered by the ambition of investigating multiple hypotheses in one 
study resulting in comparison of small patient groups. Further, utilizing second generation technol-
ogy with cool tip ablation the original idea from Cox´ surgical "core line" with one single line en-
circling the PV´s and the LAPW has been addressed in three relatively recent studies 19, 23, 24 but the 

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effect in PeAF was impossible to assess due to technical and methodological problems. Recently 
the Star AF study appears to unambiguously negate any putative advantages of the alternative strat-
egies other than PVI-only in PeAF used in that particular study. 
 
   However there is an unmet need to clarify if patients with PeAF will benefit from a combination 
of proper PVI with rigorous proof of bidirectional electrical conduction block AND electrical isola-
tion of the LAPW with equally rigorous proof of durable bidirectional block.  To our knowledge 
only one group worldwide currently conducts a randomized study to elucidate that problem 29.   
 
   It is probably impossible to obtain 100% long term electrical conduction block in one procedure 
in all patients. However, in our EP-laboratory at Gentofte Hospital we frequently do add LAPWI to 
the lesion set on an empirical basis when, during the procedure, this option is perceived to be ra-
tional. With the current state of the art (not including SF catheters) we experience first that estab-
lishing proven LAPWI is relatively fast in most patients  and second at re-do procedures the prelim-
inary experience is that these BOX lesions tend to persist (i.e. still be blocked). Thus we believe that 
a combination of the latest technological developments and procedural techniques will allow a suf-
ficiently high share of permanently isolated PVs and LAPWs during the index procedure to enable 
us to show putative advantages of that lesion set. 
 
Important technological improvements and developments of procedures  
- Third generation technological developments to optimize ablation lesions using contact force (CF) 
and time-force-temperature-impedance integration have become an integral part of AF- related pro-
cedures in our EP lab. Moreover, recently the surround flow technology (SF) offering even more 
efficient cooling than seen before has been integrated with the Smarttouch ® technology. 
- Rigorously proving bidirectional electric block over all ablation lines to ensure PVI and LAPW 
isolation. 
- Allowing proper intra-procedural waiting time supplied with adenosine testing for dormant con-
duction to detect and ablate early reconduction. 
Caveats - collateral damage 
   With larger lesion sets (such as PVI + LAPWI) and more efficient lesions - e.g. with SF Technol-
ogy - the risk of damaging tissue surrounding the LA might increase. Most importantly the esopha-
gus is notoriously prone to heat related lesions, ulcerations and eventually fatal fistulae. 2010 Halm 
et al. from Leipzig 31 published their data on 185 patients monitored with an esophageal temperature 
probe during LA ablation procedures. At esophagoscopy 1 day post procedure they found RFA re-
lated lesions in 14,5 % of the patients ranging from small superficial ulcer-like lesions to larger 
hemorrhagic lesions. Maximal esophageal temperature averaged 41,4 º C in patients without lesions 
and 42,6 ºC in patients with lesions. No lesions were found if max temperature was ≤ 41 º C. Later 
Knopp et al 32 found superficial thermal esophageal lesions in 11 % of 425 patients undergoing LA 
ablation using a cooled tip catheter in a steerable sheath. However, recently a Japanese group, per-

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forming PVI for AF, allowed esophagus temperatures up to 42 º C before pausing ablation. They 
found a range of lesions from erythema to frank ulcers in 25% of patients 33.   
Burning questions in ablation for PeAF  - Aims of study: 
   There needs to be done a sufficiently powered randomized multicenter trial utilizing the latest 
technology to clarify if LAPWI as an adjunct to PVI is beneficial as a first procedure strategy in 
PeAF.  
   However, because of the substantial economical and logistical burden of such a study we suggest 
to first conduct a minor non-randomized, single center study. The aims of such as study is to clarify: 
1) Utilizing SF-Smarttouch technology is it feasible to obtain PVI + LAPWI within a reasonable 
procedure- and fluoroscopy time ? 
2)  Is PVI + LAPWI with this potentially efficient technology safe ? 
3)  Is PVI + LAPWI durable ? 
4) To uncover trends regarding the intermediate term effect on arrhythmia recurrence of this treat-
ment ? 
Depending on the outcomes of this study the obtained data will aid in the design of a randomized, 
study comparing the effects of PVI vs. PVI + LAPWI. 
 
 

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3 BOX - PeAF – feasibility study 
3.1. Proposal of study  
 
   It is clinically and scientifically important to clarify if LAPW isolation as an adjunct to PVI in 
PeAF as a first line therapy is feasible and safe when utilizing the latest generation of ablation tech-
nology.  
 
3.2 Primary aims  
 
   In patients who undergo first ablation for PeAF with WACA-PVI the addition of anchored lines 
connecting the zeniths of the superior pulmonary veins (roof) and the nadirs of the inferior pulmo-
nary veins with proven isolation of the LA posterior wall (LAPW-isolation, LAPWI) is feasible, 
safe and durable. 
 
Feasibility: Descriptive: In patients with PeAF and established WACA-PVI it is possible to estab-
lish complete electrical isolation (bidirectional conduction block) of the LAPW by ab-
lating a superior and inferior line connecting the PVs within a reasonable prolongation / 
increase of procedure-, ablation- and fluoroscopy time.  
Safety:  
Hypothesis to be tested (see 3.4). Guided by a temperature probe in the esophagus 
WACA-PVI+LAPWI can be achieved without increasing the incidence of inflamma-
tion/ injury to the esophageal epithelial lining as proven by endoscopy on the day after 
the procedure and compared to reported incidences of up to 30% in recently published 
studies.  
 
Descriptive: WACA-PVI+LAPWI can be achieved without increasing the risk of peri-
cardial effusion and tamponade as proven by post-procedure TTE. 
Durability: Descriptive: At a per protocol interventional control procedure (independent of symp-
toms) 3 months after the index procedure a large proportion of LAPWs of PV´s will re-
main durably isolated. 
3.3 Secondary aims   
1) 
To monitor and report the aggregate signs of AF related arrhythmias as measured by an 
implanted ILR during months 0 to 6 at follow-up after WACA-PVI + LAPWI. 
 
To monitor and report the symptoms of arrhythmia with validated questionnaires dur-
ing the first 6 months F-U post procedure. QOL studies. 
2) 
Repeat the above for 6 - 12 months post procedure. 

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3.4 Hypothesis (see paragraph 3.2, safety) 
H1: By esophagoscopy the day after successful WACA-PVI + LAPWI the proportion of 
inflammation or visible injury in the esophagus induced by the ablation procedure is 
less than 0.3 
H0: By esophagoscopy the day after successful WACA-PVI + LAPWI the proportion of 
inflammation or visible injury in the esophagus induced by the ablation procedure is 
more than or equal to 0.3 
3.5 Flow sheet  
 
See appendix A 
3.6 Methods 
   A non-randomized single center study with consented participation of 23 eligible consecutive 
patients referred for radio frequency ablation for PeAF  
3.6.1 Inclusion criteria:   
 
- Symptomatic PeAF (EHRA Symptom class II or more).  
 
- Failing at least one AAD class I-IV. 
 
- Aggregate duration of persistent AF more than 3 months and less than 12 months. 
 
  during any time period prior to study entry.  
 
- Age between 18 years and 80 years. 
 
3.6.2 Exclusion criteria: 
  
- Former ablation or surgery in the left atrium. 
 
- Former valve surgery. 
 
- LA diameter (TTE-PLAX) > 52 mm in males and  > 47 mm in females  
 
- Severe mitral valve disease (stenosis or regurgitation) . 
 
- LVEF < 35 %. 
 
- Implanted pacemaker or ICD leads. 
 
- Pregnancy or susceptibility to that. 
 
- Severe other disease that may hamper adherence to study protocol. 
 
- Intolerance to amiodarone. 
 
- Participation in other clinical research studies.  
 
3.6.3 Data handling  
   The procedures will be conducted in compliance with our standards for AF ablations and as speci-
fied in appendices A and B. All data to be analyzed in this study will be generated within the 
framework of this study protocol. There will be no transfer of data from the patient´s hospital files 
to the study other than data generated as part of this study  
 

René Worck, MD, Ph.D.  Copenhagen November 2015  
PeAF box feasibility ver 2.3 
14 
 
Descriptive data:  
Feasibility: Time consumption (min.), use of X-ray (mGy), ablation time (min.) and energy deliv-
ery (watt x sec.) are registered when WACA-PVI is completed and compared to the same values at 
the end of the procedure. An estimate of the percentage increase of the procedure parameters due to 
the added LAPWI will be calculated. In the event that LAPWI cannot be achieved within 20 min 
additional ablation time after WACA-PVI then LAPWI will be considered not achievable.  
 
Safety: The unlikely occurrence of pericardial effusion will be estimated and measured by TTE 
from subxiphoid and parasternal windows immediately after the procedure and compared to prepro-
cedure echo measurements. 
 
Durability: At the follow-up procedure after 3 months a single transseptal puncture will be done 
and the durability of bidirectional block of the PV´s and the LAPW will be checked  with a soft 20 
polar catheter (Pentarray ®). If electrical conduction gaps in the ablation lines are detected a second 
TS puncture will be performed and an ablation catheter inserted into the LA. Then the precise local-
ization of gaps will be noted and related to the data from the index procedure (force-time integral, 
ablation index, esophagus temperature) for each point before gap closure with RFA. Secondary 
aims (paragraph 3.3): The patients will be asked to answer the AFEQT 20 item validated ques-
tionnaire 34 (see ref.; full questionnaire not append in protocol) on quality of life in patients with 
atrial fibrillation prior to the ablation and at 3, 6 and 12 months post ablation. The implanted ILR 
will be programmed to diagnose AF and AF related arrhythmias with the best achievable sensitivity 
and specificity. There will be a routine reading and clearing of device at 1, 3, 6, 9 and 12 months 
after the index procedure. Further the patients will be instructed to have the device read if they ex-
perience palpitations or other AF related symptoms. 
 
Esophagus data (hypothesis testing, safety): Endoscopies will be performed the day after the pro-
cedure and video material from each endoscopy will be evaluated by two independent gastroenter-
ologists. If any reaction or other pathology is encountered in the esophagus any decision on follow-
up or treatment will be at the discretion of the gastroenterologist. 
 
All data and calculations obtained in this study will be kept on storage for 5 years after the results 
have been published.  
3.7 Statistical Considerations 
   There will be no randomization or direct between-groups comparisons. Although this study is 
primarily exploratory and descriptive in nature we will formally test the hypothesis given in para-
graph 3.4. Thus the sample size calculation of this study hinges on the need to demonstrate  - with a 
reasonable power - that putative esophageal reactions to the WACA-PVI + LAPWI procedure do 
not exceed earlier findings after PVI alone.  

René Worck, MD, Ph.D.  Copenhagen November 2015  
PeAF box feasibility ver 2.3 
15 
 
Calculation of sample size and power: 
   a) The outcome of esophagoscopy on day 1 after ablation in the LA is considered to be either pos-
itive (inflammation or other esophageal reaction is noted) or negative (no  reaction). Therefore the 
probability distribution of outcomes of esophagoscopy will behave binomially. 
b) Recent data indicate that esophageal reactions can be observed in the range of 10 % (proportion 
= 0.1) up to 30 % (proportion = 0.3) with the second generation ablation technology.  We would be 
interested in showing that the proportion of esophageal reactions to WACA-PVI + LAPWI does not 
exceed proportions reported earlier (i.e. render probable that the proportion of any visible esopha-
geal reaction to ablation is less than 0.3) 
c) Setting as comparator that the underlying proportion (P) of patients subjected to this treatment 
that experience esophageal reactions is 0.3 or more AND assuming that the "true" proportion in our 
study is 0.1 then when:  
 
- P = 
 
  
0.3  
 
- One-tailed α =  
 
0.05 
 
- "true" proportion = 
 
0.1 
 
- recruiting 23 patients will yield 80 % power to reject the (H0) hypothesis that the proportion expe-
riencing esophageal reactions is equal to or higher than the 0.3. 
Based on these calculations we aim to recruit 23 patients for the study.        
The above computations were aided by the software program (IBM/ SPSS - Sample power ® ver. 
3.0.1) 
Post - hoc analyses: Statistical analysis of input - and output data will be performed using 
IBM/SPSS ® ver. 22 using appropriate statistical methods.  
3.8  Risks, inconvenience and patient exposure to adverse events 
   A) Since participating patients are all scheduled for PVI the added risk relate to the elements add-
ed by the study protocol. Directly related to the procedure are: 1) Added ablation (LAPW) com-
pared to PVI alone. This increases the amount of ablation with estimated 30%, increases the total 
procedure time with an estimated 10% and increases the total fluoroscopy dose area product (DAP) 
with an estimated 5-10%.  2) A mandatory second procedure after 3 months. This procedure will be 
minor in most patients.  
   B) Risk to the oesophagus. Although inflammatory reactions and even devastating fistulae after 
ablation at or near LAPW are mentioned in the literature (including recently). We have never in our 
setting  (15 years) experienced any clinical manifestations of damage to the oesophagus when per-
forming ablation procedures - including  PVI + BOX lesion sets. On the other hand this has not 
been studied systematically with oesophagoscopy. Thus the detection of subclinical superficial in-

René Worck, MD, Ph.D.  Copenhagen November 2015  
PeAF box feasibility ver 2.3 
16 
 
flammation of the oesophageal wall in this study is a possibility and is in fact the pivotal safety pa-
rameter under study. The oesophagus temperature is monitored closely with a temperature probe 
during the procedures and the ablation process is tailored to avoid damage. 
   C) X-ray exposure. It is estimated that adding BOX to PVI in the first procedure will add extra 0,5 
mSv. and the obligatory follow up procedure after 3 months an extra 3-4 mSv. This might increase 
the lifetime risk of developing mortal cancer from around 45% to 45,01 % (one in 10000 pts.).   
   D) Implantation of loop recorder (ILR). Is a minor surgical maneuver with subcutaneous insertion 
of a chip measuring 2 mm  *  3 mm * 40 mm performed while the patient is still under full anesthe-
sia at the end of the ablation procedure. The overall rate of adverse events related to that device is 
an estimated 1% - 2% including pain and local infection. 
   E) Oesophagoscopy the day after the procedure. This is a common invasive routine procedure 
performed by a highly skilled gastroenterologist. International literature estimates the overall com-
plication rate to  around 0,1%. However up to 2 % of patients may experience soreness of throat or 
annoying belching post procedure. The procedure is done under light sedation and overall this add-
ed oesophagoscopy is estimated to delay discharge for two hours. 
   F) Adverse effects from amiodarone treatment. Amiodarone is a highly effective and much used 
antiarrhythmic drug with many potential adverse effects. Most important are effects on the thyroid 
hormone synthesis due to the many iodine residues in the molecule. Patients with former adverse 
reactions/ experiences with the drug will be excluded from participation and patient who do not 
tolerate the drug in the 3 week run-in period pre procedure will also be excluded and treated by oth-
er means. The remaining patients who do not experience adverse effects during run-in will continue 
the drug for 3 weeks post procedure to stabilize sinus rhythm for one to two months. 
3.9 Research ethical considerations. 
   This study is a part of the continuing effort to increase accessibility, efficiency and safety of cath-
eter ablation in persistent atrial fibrillation (PeAF) which is notoriously difficult to treat both phar-
macologically and invasively. Patients more often than not need more than one procedure to get rid 
of the disease. This study aims to establish the feasibility and safety of adding a second ablation 
element to the primary procedure in order to avoid the need for secondary procedures. Further we 
will evaluate by long term follow-up the efficacy. Patients scheduled for ablation of PeAF will be 
asked to give informed consent and participate. Participating patients will be exposed to several 
inconveniences and adverse effects (given in paragraph 3.8). 
 
   On the other hand participants  will be followed very closely for symptoms or signs of recurrent 
arrhythmia and gain access to immediate qualified treatment. Further there is a possibility that the 
participating patients (PVI + BOX) will fare better and need fewer secondary procedures compared 
to non-participants (PVI only). Atrial fibrillation is a large and increasing disease entity worldwide. 
Therefore every well conducted collection of data on new methods/ approaches may importantly 
impact the treatment of these patients worldwide  

René Worck, MD, Ph.D.  Copenhagen November 2015  
PeAF box feasibility ver 2.3 
17 
 
   It is the perception among the participating scientists that we, by conducting this study, can safely 
and in a routined manner obtain important data and still maintain both a favorable benefit/risk ratio 
for the participants and a favorable benefit/cost ratio to the surrounding society.   
3.10 Patient recruitment and informed consent 
   Consecutive patients referred with PeAF and scheduled for ablation will be contacted by mail 
informing the patients about the study and that they will be approached by telephone. There they 
will be and asked if they are willing to let the study personnel conduct a screening of their eligibility 
to participate in the study. Then, patients who are willing to receive further information will receive 
the written information material by mail and summoned for a meeting with the study group at least 
two days later. These patients will be listed in the study´s screening log.  
   The patients will be strongly advised to bring a relative or other assessor for the meeting with a 
study nurse and one of the investigators, however if most convenient to the patient, the information 
and consent can be given without the participation of an assessor. In a calm secluded environment 
in an office in the research dept. of our clinic the aims, perspectives, risks and conductance of the 
study will be discussed and a brief physical examination carried out. IF the patient is willing to par-
ticipate AND fulfill the in- and exclusion criteria THEN oral and written consent will be obtained at 
the same meeting. 
   If the patient - in spite of access to the patient information at least 2 days before the meeting has 
not decided for or against participation he or she will be granted another day´s decision time at 
home. If more convenient to the patient receipt and filing of the signed consent form can be post-
poned until the patient appears for the first study day. 
3.11 Proposed substudies (not an integral part of the main protocol) 
3.11.1 ECG study 
 Since WACA-PVI + LAPWI may affect pericardial nerves (containing vagal and 
sympathetic afferents and efferents there may be detectable effects on heart rate, heart 
rate variability, SVES, VES and intervals (PQ, QRS, QT). 
 
3.11.2 ECHO study  
 
LA contractility, LA size, LA ejection fraction, systolic and diastolic parameters. 
3.11.3 Viability of posterior wall  
 
PET? 
3.11.4 Types of recurrence  
 
(AT, Afl, AF) 
3.11.5 Gap localization at 3 month per protocol re-evaluation 
 
   As a function of lesion characteristics such as FTI/ Ablation index, power, topo-
graphic localization, esophagus temperatures 

René Worck, MD, Ph.D.  Copenhagen November 2015  
PeAF box feasibility ver 2.3 
18 
 
3.11.6 Biochemical markers  
 
  Troponin/ CKMB profile post ablation and correlation to recurrence and LA size/ 
contractility/  
3.12 Budget *) 
A) Aggregate cost of submission and approval in the regional Ethics Committee  
 
 
 
 
      
 
      Dkr.            0  
B) Estimated time consumption for study nurse/ EP technician: 
 
1) SCREENING an estimated 4:1 eligible ~ 100 screened  
50 h  
 
2) Run-in + control amiodarone ; 23 pt x 2 hours  
 
46 h 
 
3) F-U for one year: 1h/visit: 23 x 4 x 1   
 
92 h 
 
4) Telemedicine F-U /analysis ILR for one year: 5h/patient x 23 pts 115 h . 
 
Aggregate cost of technical staff:  353 h x 250kr/h 
  
       Dkr.     88250  
C) Esophagoscopy  2000 D.kr /pt x 23   
       
 
       Dkr.     69000 
D) Estimated Cost of ILR **) 
 
 
 
       DKr.  
     0 
E) Unforeseen 5 % 
 
 
 
 
      Dkr.        3145 
Budget estimate (aggregate costs) 
 
                   Danish Kroner (DKr.)  160395 
 
 
 
 
 
 
 
*) This estimate only includes what is considered extra costs due to the study protocol per se. 
Not included is the standard setup for AF ablation with an electroanatomic mapping system, cool tip force sensing abla-
tion catheter, circular mapping catheter, esophagus temperature probe, coronary sinus pace/sense catheter etc. for the 
index procedure. This and the extra revenue for suppliers due to the  F-U procedures (e.g. Circular mapping catheters, 
Temperature probes etc.) will be covered by the hospital/research institution responsible for variable production costs. 
**) Devices in stock from related studies. 
3.13 Economy and sponsorship 
   Commercial suppliers of technology pivotal to the conductance and perceived to be stakeholders 
regarding the results of this study have been approached to seek economic support for coverage of 
all or parts of the budget. “Suppliers” include but are not restricted to manufacturers of ablation 
catheters, implantable loop recorders and esophageal temperature monitoring devices. There is no 
commercial sponsorship and no sponsor-investigator relationship agreement to this study. 
   The budget will be funded by unrestricted grants donated by Biosense Webster (Denmark)  and 
CIRCA electronics (Sweden) and the research foundation belonging to the arrhythmia research 
group at Gentofte Hospital. There will be no direct or indirect payments of compensation or costs to 
the participating patients. 

René Worck, MD, Ph.D.  Copenhagen November 2015  
PeAF box feasibility ver 2.3 
19 
 
3.14 Publication policy 
   The study group consists of René Worck MD, Arne Johannessen MD, Jim Hansen MD, Michael 
Vinther MD and Ebbe Langholtz MD.  
René Worck is the author of the protocol and will be the PI and first author of publications derived 
from this study. 
The results from this study will be published in international peer reviewed periodicals inde-
pendently of the results being positive (e.g. clearly showing that the procedure under study can be 
done safely, efficiently and durably in all the enrolled patients), negative (e.g. difficult, time con-
suming and not durable to obtain the sought additional electrical blockade  in the left atrium) or 
inconclusive (e.g. the power of the data turns out to be insufficient to draw firm conclusions).   
 
 

René Worck, MD, Ph.D.  Copenhagen November 2015  
PeAF box feasibility ver 2.3 
20 
 
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9.  Katritsis DG, Pokushalov E, Romanov A et al. Autonomic denervation added to pulmonary vein 
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10.  Yamaguchi Y, Kumagai K, Nakashima H, Saku K. Long-term effects of box isolation on 
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11.  Marrouche NF, Wilber D, Hindricks G et al. Association of atrial tissue fibrosis identified by delayed 
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12.  James L.Cox. Five-Year Experience With the Maze Procedure for Atrial Fibrillation. John P.Boineau, 
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13.  Ernst S, Ouyang F, Lober F, Antz M, Kuck KH. Catheter-induced linear lesions in the left atrium in 
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14.  Kottkamp H, Tanner H, Kobza R et al. Time courses and quantitative analysis of atrial fibrillation 
episode number and duration after circular plus linear left atrial lesions: trigger elimination or 
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15.  Fassini G, Riva S, Chiodelli R et al. Left mitral isthmus ablation associated with PV Isolation: long-
term results of a prospective randomized study. J Cardiovasc Electrophysiol 2005;16(11):1150-
1156. 
 
16.  Willems S, Klemm H, Rostock T et al. Substrate modification combined with pulmonary vein 
isolation improves outcome of catheter ablation in patients with persistent atrial fibrillation: a 
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17.  Sanders P, Hocini M, Jais P et al. Complete isolation of the pulmonary veins and posterior left 
atrium in chronic atrial fibrillation. Long-term clinical outcome. Eur Heart J 2007;28(15):1862-1871. 
 
18.  Gaita F, Caponi D, Scaglione M et al. Long-term clinical results of 2 different ablation strategies in 
patients with paroxysmal and persistent atrial fibrillation. Circ Arrhythm Electrophysiol 
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19.  Tamborero D, Mont L, Berruezo A et al. Left atrial posterior wall isolation does not improve the 
outcome of circumferential pulmonary vein ablation for atrial fibrillation: a prospective randomized 
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20.  Mikhaylov E, Gureev S, Szili-Torok T, Lebedev D. Additional left atrial septal line does not improve 
outcome of patients undergoing ablation for long-standing persistent atrial fibrillation. Acta Cardiol 
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21.  Pak HN, Oh YS, Lim HE, Kim YH, Hwang C. Comparison of voltage map-guided left atrial anterior wall 
ablation versus left lateral mitral isthmus ablation in patients with persistent atrial fibrillation. 
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22.  Estner HL, Hessling G, Biegler R et al. Complex fractionated atrial electrogram or linear ablation in 
patients with persistent atrial fibrillation--a prospective randomized study. Pacing Clin 
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23.  Chilukuri K, Scherr D, Dalal D et al. Conventional pulmonary vein isolation compared with the "box 
isolation" method: a randomized clinical trial. J Interv Card Electrophysiol 2011;32(2):137-146. 
 
24.  Lim TW, Koay CH, See VA et al. Single-ring posterior left atrial (box) isolation results in a different 
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25.  Saad EB, Slater C. Complete Isolation Of The Left Atrial Posterior  Wall (Box Lesion) To Treat 
Longstanding Persistent Atrial Fibrillation. J.Atrial Fibrillation 7[4], 6-9. 2015.  
 
 
26.  Kim JS, Shin SY, Na JO et al. Does isolation of the left atrial posterior wall improve clinical outcomes 
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27.  Dixit S, Marchlinski FE, Lin D et al. Randomized ablation strategies for the treatment of persistent 
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28.  Verma A, Jiang CY, Betts TR et al. Approaches to catheter ablation for persistent atrial fibrillation. N 
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29.  Natale A, Bai R, Di BL, Tondo C. Outcome of Atrial Fibrillation Ablation After Permanent Pulmonary 
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31.  Halm U, Gaspar T, Zachaus M et al. Thermal esophageal lesions after radiofrequency catheter 
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32.  Knopp H, Halm U, Lamberts R et al. Incidental and ablation-induced findings during upper 
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33.  Kuwahara T, Takahashi A, Takahashi Y et al. Incidences of esophageal injury during esophageal 
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34.  Spertus J, Dorian P, Bubien R et al. Development and validation of the Atrial Fibrillation Effect on 
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René Worck, MD, Ph.D.  Copenhagen November 2015  
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Appendix A.  PeAF-BOX - feasibility.  Flow-sheet 
 
 
PeAF screening 
 
 
Inclusion and exclusion according to criteria 
 
Eligible + informed consent 
 
 
Amiodarone: Continue or start for a run -in period of 3 weeks prior to procedure. No other class 3 
or class 1 AAD allowed  
 
 
 
 
 
 
 
 
exclude if amiodarone not tolerable 
 
 
 
  
Day 0 
WACA-PVI + LAPWI procedure incl. cardioversion if necessary  
 
 
 
 
 
  
Prove bidirectional PVI and LAPWI incl. adenosine test for dormant  
 
conduction 
 
 
 
Wait 30 minutes and test bidirectional PVI and LAPWI again  
 
 
 
  
Close gaps and prove bidirectional PVI and LAPWI 
 
 
 
 
  
Implant ILR 
 
  
TTE  immediately post procedure 
 
 
Day 1 
Oesophagoscopy 
 
 
 
Day 28  
Stop amiodarone 
 
 
 
Day 90 
Mandatory re-procedure  
 
      - Test PVI + LAPWI , identify, characterize, close gaps 
         ILR 
 
 
 
 
 
 
   monitoring  
 
      - if symptomatic arrhythmias after day 60 diagnose and ablate 
 
Day 180  
Symptom score  
 
Day 360  
Symptom score 
 
 
 
 

René Worck, MD, Ph.D.  Copenhagen November 2015  
PeAF box feasibility ver 2.3 
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Appendix B.  PeAF-BOX – feasibility - Procedure details 
 
A) Topographical registration in the left atrium: 
The operator will ablate the circles and lines in a point-by-point fashion. This allows for the 
registration of each point according to the guide given in the sketch below. 
For each ablation point the topography, contact force, time, impedance drop, power and the 
concomitant temperature in the esophagus will be registered 
Annotation guide for LA ablations 
 
 
 
 
B) Esophagus temperature. We aim to keep measured esophagus (ESO) temperatures below a 
maximum of 41.5° C while still attempting to obtain durable lesions on the LAPW. To 
achieve that goal as a main rule: 
1) Ablate at the LAPW with max energy output 20-25 watts (maximum) 
2) If ESO temp reaches 39.5° C stop ablating and check if the temperature continues to rise 
to or above 41.5°  
3) If the temperature stays below 40° decrease the energy output and/or decrease the con-
tact force (> 10 grams) and continue ablating keeping the ESO temperature ≤ 40° for a 
maximum of  15 seconds at the same point if deemed necessary. 
4) If the ESO temp rises above 41.5 ° and there are still signals at that point then wait until 
complete cool down. Then ablate again at the same point using less power and less con-
tact force. 
5) If abatement of signals at that point is not achievable using the above algorithm then at-
tempt if possible to ablate close to the point. 
6) If impossible to obtain block using this algorithm then the patient will be classified as 
“LAPWI (or PVI) not feasible.”