Else ie Edi o ial Sys em( m) o In e na ional Jou nal o Ca diology
Manusc ip D a
Manusc ip Numbe : IJC-D-14-00422R1
Ti le: Ce eb al mic oemboliza ion du ing a ial ib illa ion abla ion:compa ison o di e en single-sho
abla ion echniques
A icle Type: O iginal A icle
Keywo ds: a ial ib illa ion, pulmona y ein isola ion, ansc anial Dopple , ce eb al mic oemboli
Co esponding Au ho : D . Alexand a Kiss,
Co esponding Au ho 's Ins i u ion:
Fi s Au ho : Alexand a Kiss
O de o Au ho s: Alexand a Kiss; Edina Nagy-Balo, MD; Gábo Sándo i, MD; Is án Édes, MD, PhD,
Dsc; Zol án Csanádi, MD, PhD
Manusc ip Region o O igin: HUNGARY
Abs ac : Backg ound: Clinically silen ce eb al ischemia (SCI) de ec ed by di usion-weigh ed MRI has
been epo ed in 5-40% o pa ien s unde going pulmona y ein isola ion (PVI). Al hough ini ial epo s
sugges ed a high a e o SCI wi h phased adio equency (RF) abla ion on use o he pulmona y ein
abla ion ca he e (PVAC), he incidence was subsequen ly ma kedly educed in consequence o
p ocedu al modi ica ions in ecen s udies.
We analyzed ce eb al mic oemboliza ion as assessed wi h ansc anial Dopple du ing phased
RF abla ion and wi h wo o he single-sho AF abla ion echnologies: he c yoballoon (CB) and he
nMARQTM mul ipola i iga ed RF abla ion sys em.
Me hods and esul s: A o al o 89 pa ien s (mean age: 57, SD: 12 yea s; 62 male) wi h
pa oxysmal o pe sis en AF, unde wen PVI. Phased RF was used acco ding o he ini ial p o ocol in 7
pa ien s (PVAC G oup I), wi h p ocedu al modi ica ions and a newe (14.4) e sion o he RF gene a o
in 37 pa ien s (PVAC G oup II) and wi h he mos ecen ( e sion 15.0) gene a o in 18 pa ien s (PVAC
G oup III). Abla ion was pe o med wi h he CB in 13 and wi h he nMARQ sys em in 14 pa ien s.
The numbe o mic oemboli (mean+(SD) de ec ed in he middle ce eb al a e ies was
2703(918) in PVAC G oup I, 1087(542) in PVAC G oup II, 719(469) in PVAC G oup III, 1057(784)
wi h CB and 2166(1047) wi h nMARQ (p<0.01).
Conclusion: Signi ican dec eases in MES coun s we e obse ed hanks o he p ocedu al
modi ica ions and newe RF gene a o wi h phased RF. High MES coun s compa able o hose wi h he
ini ial phased RF esul ed om he use o nMARQ.
Sugges ed Re iewe s:
Ms. Re . No.: IJC-D-14-00422
Ti le: Ce eb al mic oemboliza ion du ing a ial ib illa ion abla ion:compa ison o di e en
single-sho abla ion echniques.
In e na ional Jou nal o Ca diology
P o . And ew J.S. Coa s
Edi o in Chie ,
In e na ional Jou nal o Ca diology
Dea P o esso Coa s,
We a e g a e ul o he Edi o s o In e na ional Jou nal o Ca diology and he e iewe o he
e alua ion o ou manusc ip ”Ce eb al mic oemboliza ion du ing a ial ib illa ion
abla ion:compa ison o di e en single-sho abla ion echniques. (Re . No.: IJC-D-14-00422)
as well as o he oppo uni y o esend i s e ised e sion. Please ind ou esponses and he
e ised pape a ached. We did ou bes o espond o all ques ions and conce ns o he
e iewe and o modi y he manusc ip acco ding o he /his sugges ion.
We eally app ecia e you conside a ion.
Since ely,
Alexand a Kiss MD
Zol an Csanadi MD
Co e Le e
Commen s om he edi o s and e iewe s:
Re iewe #1: The main objec i e o his clinical s udy is o assess and quan i y he
mic oemboli p oduced by di e en abla i e ca he e s and me hods in pa ien s ha unde wen
ca he e abla ion o a ial ib illa ion.
The objec i e is in e es ing in i sel and u he mo e because he selec ed me hodology
includes PVAC ca he e s and RF sou ce. I is al eady known since a ew yea s, how he
o iginal PVAC me hod p oduce ce eb al mIc oemboli.
So he au ho s using he same abla ion p o ocol o pulmona y ein isola ion in all he pa ien s
included, compa e he incidence and quan i y he mic oemboli and i s ma e ial solid o ae eal,
p oduced wi h he old and he new echnology o PVAC al oge he wi h c yoabla ion and also
wi h he new sys em o consecu i e RF deli e y applied h ough a new b and i iga ed
ca he e by Biosense Webs e .
The epidemiological impo ance o a ial ib illa ion makes o i an impo an issue,
u he mo e because many abla ed pa ien s oday a e young and wi hou any o he disease.
Ce eb al mic oin a c ion is hen a big issue o be s udied.
Conce ning he me hodology as he au ho s poin ou being a single cen e s udy, he
numbe s o pa ien s in each g oup a e low, o ob ain a hea y weigh on s a is ical analysis.
Besides i is no a andomized s udy.
Ano he limi a ion is he me hod selec ed by he au ho s o dopple analysis du ing he
p ocedu e o he mdiddle ce eb al a e ies. Ce ainly his objec i e is weake and should be
supplemen ed by p e and pos ce eb al MR.
In any case as each me hodology could se e as con ol o he es , I induce ha he esul s
a e uly alid. I seems ha mos o he mic oemboli a e gas and also ha he PVAC I, and
he new Biosense ca he e p oduce mo e mic oemboli ha he ammended PAVC II and III
al oge he wi h c yobla ion.
Conce ning p eabla ion an icoagula ion he au ho s should s a e exac ly he pe iod i has been
p esc ibed.
We changed he ex in he Me hods / Pa ien s sec ion and included his in o ma ion:
”1. P e-abla ion ea men wi h a i amin K an agonis (VKA) o a minimum o 3 weeks and
a he apeu ic (abo e 2.0) in e na ional no malized a io (INR) con i med on he day o he
p ocedu e, and ac i a ed clo ing ime (ACT) le els abo e 300 s du ing abla ions.”
The manusc ip has same i ems yped in black and his mus be changed.
We ealized ha some pa s o he ex appea ed in bold and I alic in he PDF gene a ed
du ing online submisson, despi e he Wo d ile we submi ed did no con ain such
sec ions. We kindly ask o you echnical assis ance o sol e his p oblem in case i
occu s again du ing his esubmission.
Bibliog aphy is co ec and app op ia e.
The ables and igu es a e ap op ia e bu need ab e ia u es, o any one used in hem.
Comple e lis o ab e ia ions we e included o all ables and igu es in he e ised
manusc ip .
The igu e 1 need a de ailed ex explaining each o he panels and wha is seen in any o
hem, o he wise i canno be unde s ood.
Figu e 1 has been econs uc ed wi h a ows and labels o cla i ica ion. In addi ion
igu e legend has been modi ied o acili a e in e p e a ion.
”Bila e al Mul i equency T ansc anial Dopple Moni o ing o he Middle Ce eb al A e ies
(a) Demons a ion o beam alignmen o bo h igh and le sided MCA and ACA. Con inuous
yellow line indica es he loca ion o moni o ing a 55 mm insona ion dep h (MCA).
(b) MCA wa e o m.
A ows on igh panel indica e he high in ensi y ansien signals co esponding o ce eb al
mic oemboli du ing PV angiog aphy.
MCA, middle ce eb al a e y; ACA, an e io ce eb al a e y ”

Au ho Ag eemen Fo m – In e na ional Jou nal o Ca diology
Manusc ip Ti le: Ce eb al mic oemboliza ion du ing a ial ib illa ion abla ion:
compa ison o di e en single-sho abla ion echniques
Lis o all Au ho s: Alexand a Kiss, Edina Nagy-Baló, Gábo Sándo i, Is án Édes, Zol án
Csanádi
Co esponding Au ho : Alexand a Kiss
This s a emen is o ce i y ha all au ho s ha e seen and app o ed he manusc ip
being submi ed, ha e con ibu ed signi ican ly o he wo k, a es o he alidi y and legi imacy
o he da a and i s in e p e a ion, and ag ee o i s submission o he In e na ional Jou nal o
Ca diology. We a es ha he a icle is he Au ho s' o iginal wo k, has no ecei ed p io
publica ion and is no unde conside a ion o publica ion elsewhe e. We adhe e o he s a emen
o e hical publishing as appea s in IJC 2013 (Shewan LG e al 2013 in p ess).
On behal o all Co-Au ho s, he co esponding Au ho shall bea ull esponsibili y o he
submission.
*Au ho Ag eemen Fo m
Ms. Re . No.: IJC-D-14-00422
Ti le: Ce eb al mic oemboliza ion du ing a ial ib illa ion abla ion:compa ison o
di e en single-sho abla ion echniques.
In e na ional Jou nal o Ca diology
Responses o Re iewe #1
Commen s om he edi o s and e iewe s:
Re iewe #1: The main objec i e o his clinical s udy is o assess and quan i y he
mic oemboli p oduced by di e en abla i e ca he e s and me hods in pa ien s ha unde wen
ca he e abla ion o a ial ib illa ion.
The objec i e is in e es ing in i sel and u he mo e because he selec ed me hodology
includes PVAC ca he e s and RF sou ce. I is al eady known since a ew yea s, how he
o iginal PVAC me hod p oduce ce eb al mIc oemboli.
So he au ho s using he same abla ion p o ocol o pulmona y ein isola ion in all he pa ien s
included, compa e he incidence and quan i y he mic oemboli and i s ma e ial solid o ae eal,
p oduced wi h he old and he new echnology o PVAC al oge he wi h c yoabla ion and also
wi h he new sys em o consecu i e RF deli e y applied h ough a new b and i iga ed
ca he e by Biosense Webs e .
The epidemiological impo ance o a ial ib illa ion makes o i an impo an issue,
u he mo e because many abla ed pa ien s oday a e young and wi hou any o he disease.
Ce eb al mic oin a c ion is hen a big issue o be s udied.
Conce ning he me hodology as he au ho s poin ou being a single cen e s udy, he
numbe s o pa ien s in each g oup a e low, o ob ain a hea y weigh on s a is ical analysis.
Besides i is no a andomized s udy.
Ano he limi a ion is he me hod selec ed by he au ho s o dopple analysis du ing he
p ocedu e o he mdiddle ce eb al a e ies. Ce ainly his objec i e is weake and should be
supplemen ed by p e and pos ce eb al MR.
In any case as each me hodology could se e as con ol o he es , I induce ha he esul s
a e uly alid. I seems ha mos o he mic oemboli a e gas and also ha he PVAC I, and
he new Biosense ca he e p oduce mo e mic oemboli ha he ammended PAVC II and III
al oge he wi h c yobla ion.
Conce ning p eabla ion an icoagula ion he au ho s should s a e exac ly he pe iod i has been
p esc ibed.
We changed he ex in he Me hods / Pa ien s sec ion and included his in o ma ion:
*De ailed Response o Re iewe s
”1. P e-abla ion ea men wi h a i amin K an agonis (VKA) o a minimum o 3 weeks and
a he apeu ic (abo e 2.0) in e na ional no malized a io (INR) con i med on he day o he
p ocedu e, and ac i a ed clo ing ime (ACT) le els abo e 300 s du ing abla ions.”
The manusc ip has same i ems yped in black and his mus be changed.
We ealized ha some pa s o he ex appea ed in bold and I alic in he PDF gene a ed
du ing online submisson, despi e he Wo d ile we submi ed did no con ain such
sec ions. We kindly ask o you echnical assis ance o sol e his p oblem in case i
occu s again du ing his esubmission.
Bibliog aphy is co ec and app op ia e.
The ables and igu es a e ap op ia e bu need ab e ia u es, o any one used in hem.
Comple e lis o ab e ia ions we e included o all ables and igu es in he e ised
manusc ip .
The igu e 1 need a de ailed ex explaining each o he panels and wha is seen in any o
hem, o he wise i canno be unde s ood.
Figu e 1 has been econs uc ed wi h a ows and labels o cla i ica ion. In addi ion
igu e legend has been modi ied o acili a e in e p e a ion.
”Bila e al Mul i equency T ansc anial Dopple Moni o ing o he Middle Ce eb al A e ies
(a) Demons a ion o beam alignmen o bo h igh and le sided MCA and ACA. Con inuous
yellow line indica es he loca ion o moni o ing a 55 mm insona ion dep h (MCA).
(b) MCA wa e o m.
A ows on igh panel indica e he high in ensi y ansien signals co esponding o ce eb al
mic oemboli du ing PV angiog aphy.
MCA, middle ce eb al a e y; ACA, an e io ce eb al a e y ”
Elec ophysiology Inc., Lowell, MA, USA), which was posi ioned selec i ely in each PV. The
elec ical conduc ion p ope ies o he PV we e assessed on he basis o he signals eco ded
by he PVAC elec odes a e placemen inside he os ium. Be o e he i s RF applica ion a
each PV, he posi ions o he elec odes ela i e o he PV os ium we e always con i med by
means o con as injec ion h ough he FlexCa h shea h. Ca e was always aken o apply he
RF ou side he PV in he an al egion, a ge ing po en ials o high ampli ude on as many
elec odes as possible o each applica ion. RF ene gy was applied o 60 s, usually 3-4 imes
pe PV, un il PVI was achie ed. The a ge empe a u e was 60 °C, measu ed sepa a ely o
all bipoles. Any elec ode pai ha ailed o each a leas 50 °C du ing RF deli e y was
swi ched o o a oid ine ec i e ED due o imp ope con ac a he elec ode- issue in e ace.
Common os ia we e isola ed by inse ing he guidewi e in o he di e en side b anches and
abla ing subsequen segmen s o he a ge ed eins. The PV conduc ion was eassessed a e
each RF applica ion, he elec odes being ad anced inside he os ium. The endpoin o he
p ocedu e was he elec ical isola ion o all PVs, as con i med by an en ance block.
The GENius RF gene a o is capable o deli e ing RF in a du y-cycled mode wi h
di e en bipola /unipola a ios o any o all o he elec odes on he PVAC. Th ee
consecu i e e sions o he GENius RF gene a o (Med onic Inc. , Minneapolis, MN, USA)
we e used in he cou se o ecen yea s, also coupled wi h some p ocedu al modi ica ions as
ollows:
1. PVAC G oup I. Ini ial se ies o abla ions we e pe o med wi h he use o so wa e e sion
14.3 o he GENius gene a o . Bipola /unipola RF applica ion was s a ed a a a io o 4:1
o each PV and changed o a bipola /unipola a io o 2:1 o a deepe lesion when a
su icien educ ion in local elec og am ampli ude could no be achie ed a e mul iple RF

deli e ies. No a emp s we e made o a oid he po en ial in e ac ion be ween he i s and he
las elec ode (E1-E10) in he PVAC.
2. PVAC G oup II. Abla ions we e pe o med wi h so wa e e sion 14.4 o he GENius
gene a o . Modi ica ions in he p ocedu al echnique we e implemen ed in his g oup o
pa ien s as ollows. Po en ial in e ac ion be ween he mos dis al (E1) and he mos p oximal
(E10) elec odes was conside ed and simul aneous EDs on hese poles we e a emp ed only
a e luo oscopic assessmen o he in e elec ode dis ance, which was conside ed adequa e i
he space be ween E1 and E10 was a leas double he ixed 3-mm in e elec ode dis ance as
assessed om mul iple p ojec ions. Fu he mo e, abla ions we e s a ed in he 2:1 mode and
changed o 1:1 in hose a e ins ances when adequa e ampli ude change and PVI could no be
achie ed a e mul iple RF applica ions. In addi ion, he dis al ci cula segmen o he PVAC
ca he e was subme ged and cap u ed by he in oduc ion de ice in a saline ba h p io o
inse ion in o he FlexCa h shea h. This maneu e was used o p e en ai en apmen a ound
he a ay and he in oduc ion o ai in o he LA h ough he anssep al shea h.
3. PVAC G oup III. Abla ions we e pe o med using he mos ecen so wa e e sion
(15.0) o he GENius gene a o . RF deli e y o E10 is no suppo ed by his so wa e he eby
excluding he possibili y o E1-E10 in e ac ion. No p ocedu al modi ica ions as compa ed o
hose in PVAC G oup II. we e implemen ed du ing hese abla ions.
CB abla ion
The echnology o CB abla ion has been desc ibed in de ail [17]. In b ie , a 28-mm
CB was used in all cases. The CB was in oduced in o he PV os ium o e an inne lumen
mapping ca he e (Achie e, Med onic Abla ion F on ie s LCC, Ca lsbad, CA, USA) which is
capable o mapping PV po en ials be o e, du ing and a e c yo applica ions. The bes
possible occlusion o he PVs was acili a ed by he s ee able shea h and by posi ioning he
guidewi e in a PV b anch o p o ide maximal suppo . Fu he mo e, all special maneu e s
desc ibed p e iously, such as he “pull-down” o he “hockey s ick” echniques, we e used as
needed [21].
PV occlusion was assessed by means o a hand-held injec ion o con as medium
(Op i ay Co idien Deu schland GmbH, Neus ad /Donau, Ge many) h ough he injec ion
side-po o he A c ic F on ca he e . A minimum o wo 5-min eezing cycles we e applied
pe PV. The balloon was eposi ioned o each applica ion, p e e ably wi h he guidewi e
si ua ed in a di e en b anch o he PV in o de o maximize he e ec o eezing a di e en
aspec s o he os ium. Be o e he s a o abla ion o he sep al eins, a quad ipola ca he e
was placed in he supe io ca al ein, whe e cons an cap u e o he igh ph enic ne e could
be achie ed. One s imulus a maximal ou pu was deli e ed e e y 5 s, wi h manual
assessmen o he diaph agma ic mo emen . The eezing cycle was e mina ed immedia ely
i loss o weakening o he diaph agm esponse occu ed. PVI was assessed on he basis o
he signals eco ded by he Achie e wi e.
nMARQ abla ion
The nMARQ™ (Biosense Webs e , Inc., Diamond Ba , CA, USA) is a mul i-
elec ode, i iga ed RF abla ion ca he e wi h a uni-di ec ional de lec able ip. The dis al
ip sec ion is ci cula o semiluna and con ains 10 pla inum ing elec odes wi h i iga ion
holes a bo h ends o s imula ion, eco ding and abla ion. The diame e o he ci cula o
semiluna loop is a iable o accommoda e he LA ana omy. The ca he e is in eg a ed wi h
he CARTO 3 elec oana omical mapping sys em, which p o ides mapping and eal- ime
na iga ion capabili ies. Fo abla ion, he ca he e is used in conjunc ion wi h he nMARQ™
Mul i-Channel RF Gene a o , which is able o deli e RF simul aneously o mul iple
elec odes in unipola o bipola mode.
The ci cula - ip ca he e was used exclusi ely in his s udy. The ca he e was
ad anced o he LA h ough he FlexCa h guiding shea h. The 3-dimensional map o he
LA was cons uc ed by using he CARTOTM elec oana omical mapping sys em (Biosense
Webs e , Inc., Diamond Ba , CA, USA) equipped wi h Ca ome geTM so wa e (Biosense
Webs e , Inc., Diamond Ba , CA, USA). The p e-abla ion ca diac CT image o he LA wi h
he p oximal po ions o he PVs was impo ed and egis e ed o eal- ime mapping, ocusing
on he PVs and he PV an a o he LA. In addi ion, he posi ions o he elec odes ela i e o
he PV os ium we e always con i med be o e he i s RF applica ion a each PV, by means o
con as injec ion h ough he FlexCa h shea h. Ca e was aken o apply he RF ou side he PV
in he an al egion, a ge ing po en ials o high ampli ude on as many elec odes as possible
o each applica ion. RF ene gy was applied o up o a maximum o 60 s a a maximum o 20
W/elec ode in he unipola mode, wi h he a ge empe a u e se a 43 °C. Elec odes no
demons a ing he desi ed ise in empe a u e up o 40 °C du ing ene gy deli e y we e
swi ched o . The i iga ion low a e be ween RF applica ions was 4 ml/min, which was
inc eased o 60 ml/min, s a ing 5 s be o e he onse o RF applica ion and main ained un il
5 s a e e mina ion. The elec ical conduc ion p ope ies o he PVs we e assessed ia he
eco dings h ough he elec odes o he nMARQ ca he e . The endpoin o he p ocedu e was
he elec ical isola ion o all PVs, as con i med by an en ance block.
TCD eco ding and e alua ion o he MES coun
TCD eco ding was pe o med h oughou he whole pe iod o LA access ( om he
anssep al punc u e o he emo al o all ca he e s and shea hs om he LA). The ansduce
was held in place by a p op ie a y headpiece supplied wi h he sys em. The MCAs we e
bila e ally insona ed om ans empo al windows by using a mul i equency Dopple (Mul i
Dop T digi al, DWL, QL so wa e 2.8) which insona es simul aneously wi h equencies o 2
and 2.5 MHz. The sys em is capable o he au oma ic online iden i ica ion o ue MESs wi h
a sensi i i y o 100% and a speci ici y o 99.3% [22], and also o disc imina ion be ween
gaseous and solid emboli wi h a speci ici y o 96.5%[23]. The iden i ica ion o ue MESs
wi h pa allel a e ac ejec ion is possible by implemen ing an e en de ec o sys em, using a
p e iously published algo i hm o de ec high-in ensi y signals due o emboli[22]. This s ep is
ollowed by a second algo i hm using da a om he dual- equency insona ion o de e mine
whe he he MESs a e o be a ibu ed o a solid o o a gaseous embolus. Di e en ia ion is
possible because he e lec ion o ul asound powe is dependen no only on he size o he
embolus, bu also on i s composi ion and he insona ing equency used: solid emboli e lec
mo e ul asound a 2 MHz han a 2.5 MHz, whe eas he opposi e is ue o gaseous emboli.
TCD pa ame e se ings as ecommended by he consensus c i e ia [24] we e kep cons an
du ing he p ocedu es. The insona ion dep h was 45-55 mm, he sample olume was 8 mm,
and he powe was 60-100 mW. An example o a TCD eco d is gi en in Figu e 1. MES
coun s we e collec ed and e alua ed sepa a ely du ing di e en s ages o he p ocedu e, as
ollows:
1. T anssep al punc u e: he 30-s pe iod a e c ossing he in e a ial sep um wi h he
anssep al needle.
2. PV angiog aphy: con as injec ion h ough he injec ion po o he C yoCa h ca he e o
he anssep al shea h du ing PVAC o nMARQ abla ion.
3. Ene gy deli e y: om he s a un il 15 s a e he e mina ion o ED
4. The emainde o he p ocedu e: ha pa o he LA access pe iod du ing which none o he
a o emen ioned maneu e s we e pe o med.
As bila e al insona ion o he MCA could no be achie ed in all pa ien s o echnical
easons, he esul s we e p o ided as MES coun pe MCA, i.e. ei he he mean o bila e al
eco dings o he numbe om he unila e al eco ding.
S a is ical analyses
S a is ical analysis was pe o med by using IBM SPSS 20. Da a a e epo ed as means
and s anda d de ia ion (SD). In he case o Figu e 1, da a a e shown as mean and 95%
con idence in e als (95% CI). The no mali y o con inuous a iables was e alua ed by
means o he Kolmogo o - Smi no es . S a is ical di e ences be ween g oups we e
de e mined by using analysis o a iance when he da a showed no mal dis ibu ion and
homoscedas ici y (Le ene’s s a is ic); o he wise, he K uskal-Wallis es was pe o med. Fo
compa ison o he MES coun s ob ained du ing CB abla ion e sus hose du ing he o he 4
echniques, he Mann-Whi ney es was used. In all s a is ical es s a p alue below 0.05 was
conside ed as signi ican .
Resul s

Pa ien cha ac e is ics
A o al o 89 pa ien s we e en olled in he s udy. Demog aphic and clinical pa ame e s
on he pa ien s in he 5 ea men g oups a e p esen ed in Table 1. The e we e no signi ican
in e g oup di e ences in he baseline cha ac e is ics.
P ocedu al da a
P ocedu al da a a e lis ed in Table 2. The o al p ocedu e, luo oscopy, ED and LA
access imes demons a ed signi ican di e ences. The acu e success a es we e 100% in he 3
PVAC G oups, and 98% in bo h he CB and he nMARQ g oups. The sho es LA access
ime was achie ed in PVAC G oup III, while he sho es ED ime was ob ained du ing
abla ion wi h he nMARQ. The e we e no signi ican di e ences be ween he in ap ocedu al
ACT alues. Symp oma ic h omboembolic e en did no occu in any pa ien .
MES coun s
The MES coun de ec ed wi h he CB was used as a e e ence o compa ison wi h he o he
echnologies (Figu e 2, le panel). No signi ican di e ence was ound be ween he CB
g oup, PVAC G oup II (p=0.543) and PVAC G oup III (p=0.317) in he o al ce eb al MES
coun s. Howe e signi ican ly highe MES coun s we e demons a ed in PVAC G oup I
(p=0.005) and wi h he nMARQ echnique (p=0.007). The a ios o gaseous e sus solid
MESs de ec ed in he 5 ea men g oups did no di e signi ican ly (p=0.688). (Figu e 2,
igh panel)
The dis ibu ion o he MES coun s du ing di e en s ages o he p ocedu e is
depic ed in Figu e 3. A ela i ely e en dis ibu ion o embolus o ma ion was obse ed ac oss
he whole LA access ime in he CB g oup, and in PVAC G oups II and III, whe eas,
mic oemboli we e de ec ed mos ly du ing ED in PVAC G oup III and wi h nMARQ.
Discussion
Majo di e ences ha e been epo ed in he incidence o SCI a e AF abla ion wi h
a ious echnologies and wi h he di e en me hods and c i e ia applied o e alua e ce eb al
lesions. The di e si y o he pe ip ocedu al an icoagula ion ou ine in he a ious s udies
u he hampe s a di ec compa ison o he di e en AF abla ion echniques. In he p esen
s udy, we compa ed di e en single-sho abla ion ools designed o PVI wi hou addi ional
LA abla ion (eg. c ea ing long linea lesions, o abla ing complex ac iona ed elec og ams)
in pa ien s wi h simila baseline cha ac e is ics. Fu he , pe ip ocedu al an icoagula ion was
homogeneous ac oss all ea men g oups wi h unin e up ed VKA adminis a ion and
he apeu ic INR le el be o e he p ocedu e and i hepa iniza ion o a a ge ACT abo e 300 s
in ag eemen wi h cu en ecommenda ions [25]. Any di e ences demons a ed in he
numbe o mic oemboli a e he e o e uly inhe en o he abla ion echniques compa ed.
The a e o mic oemboliza ion du ing phased RF abla ion wi h he implemen a ion o
speci ic p ocedu al modi ica ions and he use o consecu i e so wa e e sions o he GENius
gene a o demons a ed a signi ican dec ease in ou s udy. The e y same end was obse ed
in ecen DW MRI s udies on he a e o new SCI lesions a e phased RF abla ion.
Impo an ly, no di e ence was de ec ed in he le el o mic oemboliza ion be ween he
p ocedu e wi h CB abla ion e sus ha wi h he PVAC a e p ocedu al and so wa e changes
had been implemen ed (PVAC G oups II and III). In con as , signi ican ly highe MES
coun s we e eco ded du ing phased RF abla ion wi h he use o he old echnique (PVAC
G oup I) and du ing abla ion wi h nMARQ (Figu e 2).
The signi ican educ ion in mic oemboliza ion wi h phased RF was clea ly ela ed o
he elimina ion o he MESs du ing he ED pe iod o he p ocedu e. Simila ly o as obse ed
in PVAC G oup I, he majo i y o he mic oemboli we e gene a ed du ing ED wi h nMARQ,
which also ep esen s a mul ielec ode RF abla ion echnology (Figu e 3). I is no ewo hy
ha MESs we e la gely gaseous in na u e in all ea men g oups.
Measu es ela ed o he educ ion in ce eb al emboliza ion wi h phased RF abla ion
The signi ican educ ion achie ed in clinically silen mic oemboliza ion, as
demons a ed by DW MRI s udies and ou own esul s, we e ela ed o e inemen s in speci ic
echnical elemen s o he phased RF abla ion, based on p eclinical da a [12,13].The
obse a ion o enhanced mic oemboliza ion wi h blended unipola :bipola ene gy deli e ed
h ough PVAC elec odes in close p oximi y o each o he was o u mos impo ance. While
his p oblem emained unknown, his was a likely common scena io, owing o he squeezed
si ua ion o he dis al PVAC loop. I should be no ed ha ac ual physical con ac be ween any
wo elec odes esul s in an elec ical sho ci cui and immedia e e mina ion o he RF
deli e y. On he o he hand, no con ac , bu a educed in e elec ode space (less han he
ixed 3 mm be ween wo neighbo ing elec odes moun ed on he dis al ci cula segmen o
he PVAC) may lead o blood and issue o e hea ing, due o a high cu en densi y. Simple
measu es o a oid his possibili y include a ca e ul luo oscopic assessmen o he elec ode
posi ions (as we did in PVAC G oup II), exclusion o simul aneous RF ED o elec odes 1 and
10, as p oposed by se e al au ho s [9-12] and a so wa e modi ica ion implemen ed in he
la es e sion o he GENius gene a o , which suppo s simul aneous RF deli e y o a
maximum o 9 elec odes (so wa e e sion 15.0; PVAC G oup III in ou s udy).
The ea lie p ac ice o s a ing ED in a 4:1 bipola :unipola mode a each PV was
changed o s a wi h a 2:1 a io in PVAC G oups II and III. The a ionale o his change was
o a oid ex ensi e bipola ED and he eby educe local hea ing be ween adjacen elec odes.
Al hough animal da a sugges ed a endency o mo e mic oemboli wi h mo e bipola RF
deli e y, he con ibu ion o his change in he educ ion o mic oemboli is unce ain.
None heless, s a ing wi h he 2:1 ins ead o he 4:1 a io is he cu en p ac ice a o he
cen e s [9-11,26].
As demons a ed in an animal model, a po en ial sou ce o gaseous emboli was he
in oduc ion o ai in o he LA ia he anssep al shea h. A signi ican ly la ge ai olume
was measu ed du ing he in oduc ion o he PVAC, possibly owing o i s mo e complex
shape as compa ed wi h a con en ional ocal RF ca he e . To p e en ai en apmen a ound
he a ay, he PVAC was subme ged and cap u ed by he in oduc ion de ice in a saline ba h
p io o inse ion in o he FlexCa h shea h.
I is no ewo hy ha , in addi ion o he p ocedu al changes as desc ibed abo e, he
GENius RF gene a o has also been modi ied in ecen yea s. An imp o ed ene gy i a ion
algo i hm was implemen ed s a ing a e sion 14.4 (PVAC G oup II), which egula es he
powe deli e y o con ol he maximum, ins ead o he a e age empe a u e, wi h a a ge o
60 °C. Fu he , his so wa e ensu es a g adual and limi ed inc ease (4 W/s) du ing a iable o
in e mi en elec ode- issue con ac , o a oid high empe a u e peaks. The impo ance o he
ca he e - issue con ac has been highligh ed since he in oduc ion o con ac o ce
measu emen o ocal RF abla ion ca he e s [27,28]. Wi h mul ipola abla ion, his becomes
e en mo e c i ical, as he main enance o good con ac simul aneously on mul iple elec odes
18. Boe sma LV, Wij els MC, O al H, We e EF, Mo ady F. Pulmona y
ein isola ion by du y-cycled bipola and unipola adio equency ene gy wi h
a mul ielec odeabla ion ca he e . Hea Rhy hm. 2008 Dec;5(12):1635-42.
19. Scha C, Boe sma L, Da ies W, e al. Abla ion o pe sis en a ial ib illa ion
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Ca diol. 2009 Oc 6;54(15):1450-6.
20. Boe sma L, Duy schae e M, Gelle JC, Scha C. The PVAC Wo kbook Remedica,
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acu e pulmona y ein isola ion in pa ien s wi h pa oxysmal a ial ib illa ion: a
p ospec i e obse a ional single cen e s udy. Eu Hea J. 2009 Ma ;30(6):699-709.
22. Russel D, B uche R. Online au oma ic disc imina ion be ween solid and gaseous
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and ollow-up, de ini ions, endpoin s, and esea ch ial design: a epo o he Hea
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TABLE
Table 1. Pa ien clinical cha ac e is ics
Va iable
CB
n=13
PVAC I.
n=7
PVAC II.
n=37
PVAC III.
n=18
nMARQ
n=14
p
Age, yea s (SD)
57(15)
54(8)
60(10)
55(12)
53(12)
0.372
Male, n (%)
9 (69)
6(85)
25(67.5)
12(67)
10(71)
Type o AF
Pa oxysmal AF, n (%)
Pe sis en AF, n (%)
11(84)
2(16)
6(85)
1(15)
25(67.5)
12(32.5)
12(67)
6(33)
10(71)
4(29)
A e ial hype ension, n (%)
7(53)
2(28)
28(75)
13(72)
8(57)
Diabe es melli us, n (%)
0(0)
2(28)
3(8)
1(5.5)
1(7)
LA sho diame e , mm (SD)
41(4)
40(4)
42(3.5)
43(6)
42(3.7)
0.825
LVEF, % (SD)
55(4)
52(8)
55(5)
54(10)
58(5)
0.325
Mean CHADS2 sco e
0.62
0.71
0.92
0.83
0.64
0.491
Mean CHA2DS2-VASc sco e
1.23
0.86
1.65
1.39
1.14
0.309
AF, a ial ib illa ion; EF, ejec ion ac ion; LA, le a ial; LV, le en icula ; CB,
c yoballoon; PVAC, pulmona y ein abla ion ca he e ;
Table 2. P ocedu al pa ame e s
P ocedu al
pa ame e s
CB
n=13
PVAC I
n=7
PVAC II
n=37
PVAC III
n=18
nMARQ
n=14
p
To al p ocedu e
ime(min)(SD)
126 (24)
89 (23)
88 (16)
86(25)
108 (25)
<0.001
Fluo oscopy ime (min)
(SD)
28.8 (8)
17.7 (8.4)
21.2 (8.8)
16.5 (5.3)
21.1(7.8)
0.002
Ene gy deli e y ime
(min) (SD)
34.2 (18.8)
16 (4.5)
14.9 (4.1)
12(2.8)
7.7(3.4)
<0.001
Le a ial access ime
(min) (SD)
80.8 (26)
70.4(22.7)
55.4 (15.1)
47.2(13.6)
75.9 (27.4)
<0.001
In ap ocedu al ACT
(s)
340
380
358
328
317
0.148
Acu e success a e (%
o isola ed PVs)
98
100
100
100
98
PV, pulmona y ein; o he ab e ia ions as abo e
FIGURE LEGENDS
Figu e 1. Bila e al Mul i equency T ansc anial Dopple Moni o ing o he Middle Ce eb al
A e ies
(a) Demons a ion o beam alignmen o bo h igh and le sided MCA and ACA. Con inuous
yellow line indica es he loca ion o moni o ing a 55 mm insona ion dep h (MCA).
(b) MCA wa e o m.
A ows on igh panel indica e he high in ensi y ansien signals co esponding o ce eb al
mic oemboli du ing PV angiog aphy.
MCA, middle ce eb al a e y; ACA, an e io ce eb al a e y
Figu e 2. Le panel: To al Mic oembolic Signal Coun in he Fi e T ea men G oups. A plo
o he mean numbe o mic oembolic signals (MESs) pe middle ce eb al a e y in each
ea men g oup, as compa ed wi h he CB g oup.
Righ panel: Ra io o Gaseous/Solid Emboli in he Fi e T ea men G oups.
(Ab e a ions as in ables)
Figu e 3. Mic oembolic Signal Coun s Du ing Di e en S ages o he P ocedu e.
(Ab e a ions as abo e)

Figu e 1
Click he e o download high esolu ion image
Figu e 2
Click he e o download high esolu ion image
Figu e 3
Click he e o download high esolu ion image