Cerebral microembolization during atrial fibrillation ablation: comparison of different single-shot ablation techniques

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 using mul ielec ode ca he e s and du y-cycled adio equency ene gy. J Am Coll 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, 2010 21. Chun KR, Schmid B, Me zne A, e al. The 'single big c yoballoon' echnique o 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 mic oemboli wi h he i s mul i equency ansc anial Dopple . S oke. 2002 Aug; 33 (8):1975-80 23. Ma kus HS, Pun e M. Can ansc anial Dopple disc imina e be ween solid and gaseous mic oemboli? Assessmen o a dual- equency ansduce sys em. S oke. 2005 Aug; 36(8):1731-4. 24. Ringels ein EB, D os e DW, Babikian VL, e al. Consensus on mic oembolus de ec ion by TCD. In e na ional Consensus G oup on Mic oembolus De ec ion. S oke. 1998; 29:725-729. 25. Calkins, H., Kuck, K. H., Cappa o, R., e al. 2012 HRS/EHRA/ECAS expe consensus s a emen on ca he e and su gical abla ion o a ial ib illa ion: ecommenda ions o pa ien selec ion, p ocedu al echniques, pa ien managemen and ollow-up, de ini ions, endpoin s, and esea ch ial design: a epo o he Hea Rhy hm Socie y (HRS) Task Fo ce on Ca he e and Su gical Abla ion o A ial Fib illa ion. Jou nal o In e en ional Ca diac Elec ophysiology, 33, 171–257. 26. Deneke T, Shin DI, Bal a O, Pos abla ion asymp oma ic ce eb al lesions: long- e m ollow-up using magne ic esonance imaging. Hea Rhy hm. 2011 No ;8(11):1705- 11. 27. Neuzil P, Reddy VY, Kau zne J, e al.Elec ical econnec ion a e pulmona y ein isola ion is con ingen on con ac o ce du ing ini ial ea men : esul s om he EFFICAS I s udy.Ci c A hy hm Elec ophysiol. 2013 Ap ;6(2):327-33. 28. Kuck KH, Reddy VY, Schmid B, e al. A no el adio equency abla ion ca he e using con ac o ce sensing: Tocca as udy. Hea Rhy hm. 2012 Jan;9(1):18-23. 29. Nagy-Balo E, Kiss A, Condie C, S ewa M, Edes I, Csanadi Z. Biophysical backg ound o ce eb al mic oemboliza ion du ing phased adio equency abla ion o a ial ib illa ion: analysis o high esolu ion da a om he abla ion gene a o . Eu opean Hea Jou nal. 2013 34 ( Abs ac Supplemen ), 1096-1097 30. Khai y P, Chau e P, Lehmann J, e al. Lowe incidence o h ombus o ma ion wi h c yoene gy e sus adio equency ca he e abla ion. Ci cula ion. 2003 Ap 22;107(15):2045-50. 31. Sau en LD, VAN Belle Y, DE Roy L, e al.T ansc anial measu emen o ce eb al mic oembolic signals du ing endoca dial pulmona y ein isola ion: compa ison o h ee di e en abla ion echniques. J Ca dio asc Elec ophysiol. 2009 Oc ;20(10):1102-7. 32. Deneke T, Schade A, Mülle P, e al. Acu e Sa e y and E icacy o a No el Mul ipola I iga ed Radio equency Abla ion Ca he e o Pulmona y Vein Isola ion. J Ca dio asc Elec ophysiol. 2013 No 14. doi: 10.1111/jce.12316. [Epub ahead o p in ] 33. Csanadi Z, Nagy-Baló E, Dank S, e al. Ce eb o ascula Complica ions Rela ed o A ial Fib illa ion Abla ion and S a egies o Pe ip ocedu al S oke P e en ion. Ca diac Elec ophysiol Clinics 2014; Ma ch (in p ess) DOI: 10.1016/j.ccep.2013.10.003 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