DOI: 10.1161/CIRCEP.114.002259

Radiofrequency Catheter Ablation of Idiopathic Ventricular Arrhythmias Originating from Intramural Foci in the Left Ventricular Outflow Tract; Efficacy of Sequential vs. Simultaneous Unipolar Catheter Ablation

Running title: Yamada et al.; RFCA of idiopathic intramural LVOT VAs

Takumi Yamada, MD1; William R. Maddox, MD2; H. Thomass McElderry, y MD D1; Harish Doppalapudi, MD1; Vance J. Plumb, MD1; G. Neal eal Ka K Kay, y, M MD D1

1

Division of of C Cardiovascular ardiovascul ularr D ul Disease, isea ease se,, Un se U University iveersity iv y off Alabama Alab bamaa at at Birmingham, Bir irmi miinggham, ham, m Birmingham, Bir irmi ir m nggha h m, A AL; L; 2C Clinical Cardiacc El Electrophysiology, Department Medicine, Georgia Regents University, Augusta, GA Elec e trophy ysio olo ogy y, D epa paart rtment nt ooff Medi icinee, Ge eorgiia Re egents U niv iv versity y, Au A gusta, a, G

Correspondence: n ndence: Takumi Yamada, MD, PhD Division of Cardiovascular Disease University of Alabama at Birmingham FOT 930A, 510 20th Street South 1530 3rd Ave S Birmingham, AL 35294-0019 Tel: +1-205-975-2404 Fax: +1-205-996-5857 E-mail: [email protected]

Journal Subject Codes: [22] Ablation/ICD/surgery

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DOI: 10.1161/CIRCEP.114.002259

Abstract:

Backgrounds-Idiopathic ventricular arrhythmias (VAs) originating from the left ventricular outflow tract (LVOT) sometimes require catheter ablation from the endocardial and epicardial sides for their elimination, suggesting the presence of intramural VA foci. This study investigated the efficacy of sequential and simultaneous unipolar radiofrequency catheter ablation from the endocardial and epicardial sides in treating intramural LVOT VAs. Methods and Results-Fourteen consecutive LVOT VAs, which required sequential or simultaneous irrigated unipolar radiofrequency ablation from the endocardial and epicardial sides for their elimination were studied. The first ablation was performed at th thee si site te w with ithh th it thee ea earl earliest rlli local ventricular activation and/or best pace map on the endocardial orr epic epicardial When car a di dial a sside. al id de. e W h the he first ablation on was was a uunsuccessful, n ucce ns ceessful, the second ablationn was was deliveredd on the th other surface. If th this sequential uunipolar niipolar ablati ablation tioon failed, ti fai aile l d, le d ssimultaneous imul imul ulta t ne neouss uunipolar nip polar a abl ar ablation bllatio on from m both bot othh sides ot siide dess was waas performed. perf pe ro The first ablation blation bla ati tion on was ass performed perrfo form med onn the the ep epicardial piccar ardi dial di all sid side de inn 9 VAs VAs A and andd endocardial end ndocar ardi ar d all sside ide iinn 5 VAs. V VA A The intramural LVOT eliminated LVO OT VAs VAs were were r ssuccessfully u ce uc cess ssfu ss full fu l y el elim imin im in nated ed d bbyy the th he sequential seequ quen enti en tial ti al (n=9) (n= n=9) 9) oorr si 9) simu simultaneous mult mu ltan lt aneo an eous (n=5) unipolar catheter a he athe at hete terr ablation. te abla ab lati la tion ti on. Simultaneous on Simu Si mult mu ltan lt aneo an eous eo us ablation abl blat atio at ionn was io was most most likely lik ikel elyy to be el be required requ re quir qu ired ir ed for for the the eliminationn off the between ablation the VAs VAs when hen he the th distance distt bet bett een tthe he endocardial ndd diall and ndd epicardial pii rdi diall abl blati ti sites sit it was >8 mm and the earliest local ventricular activation time relative to the QRS onset during the VAs of < –30 msec was recorded at those ablation sites. Conclusions-LVOT VAs originating from intramural foci could usually be eliminated by sequential unipolar radiofrequency ablation and sometimes required simultaneous ablation from both the endocardial and epicardial sides.

Key words: ventricular arrhythmia, left ventricular outflow tract, intramural focus, radiofrequency catheter ablation, unipolar

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The left ventricular outflow tract (LVOT) is the second most common site of origin of idiopathic ventricular arrhythmias (VAs) after the right ventricular outflow tract (RVOT).1-4 Although endocardial radiofrequency catheter ablation (RFCA) is highly successful for idiopathic RVOT VAs,1 epicardial RFCA is sometimes required to cure LVOT VAs because the LVOT muscle is thicker than that of the RVOT.3-6 Anatomically, successful RFCA sites of idiopathic LVOT VAs include the aortic root, endocardium underneath the aortic valve that is termed the aorto-mitral continuity (AMC), and epicardial surface of the left ventricle (LV) thatt is termed the LV V summit, s m su and can be reached by an ablation catheter through the great cardiac vein ein ((GCV) G V)) oorr a GC -6 transpericardial a di ardi dial al appro approach. roaach. ro h 22-6 The AMC and LV summi summit mit face each other o herr with the superior endd of the ot

LV muscle be bbetween bet etween them them. m.55,6,6 Th The T he av ava availability ailabilitty of ir irrigated rrigaated radi ra radiofrequency adi diofreequency qu cy (RF (RF) RF) ab RF ablation blaatiion cat catheters athee at to create deeper p RF per F llesions esio es ionns ha io hass si sign significantly g ific gn iffic ican antlyy impr an im improved mpr p ov o ed the the ooutcome utccome ut come ooff RF RFCA CA A ooff id idio idiopathic iopa io p th pa thic ic LVOT LV V VAs.7 However, w wever, RFCA CA off iidiopathic diop di opat op athi at hic LV hi LVOT OT V VAs As iiss st stil still illl so some sometimes meeti time m s ch me challenging hal a le leng nggin i g be beca because c use of the t close proximity of VA origins to the coronary arteries,6,7 a thick epicardial fat pad,6,7 and intramural sites of origins4. There are three alternative configurations for treating intramural VA origins in this region that may overcome these limitations: first, unipolar RF current may be applied in a sequential manner from the endocardium followed by the epicardium (or vice versa); second, unipolar RF current can be applied simultaneously from two catheters positioned on the endocardial and epicardial LVOT; third, RF current may be applied in a bipolar configuration from the distal electrode of the two catheters8. However, bipolar RFCA may not be effective when there is an impedance mismatch between the AMC and GCV as the higher impedance of either electrode will

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limit the current that can be applied to both electrodes. The purpose of this study was to determine the efficacy of the sequential unipolar and simultaneous unipolar RFCA configurations when used on the endocardial and epicardial sides of the myocardium to treat intramural LVOT VAs.

Methods Patient characteristics The study population consisted of 64 consecutive patients from a single center (30 ( men,, mean age 54+15 years (range 18 to 83)) with symptomatic idiopathic sustained ventricular ventri ricu ri cula cu larr ta la tach tachycardias chyc ch yccar arddi di (VTs) (n=14), 4), ),, nnon-sustained o -su on s st s aiined VTs (n=15) or premature premattur uree ventricular cont contractions ntrractions (PVCs) (n=35), nt (n=33 which presumable u umable um origin origins ns we were eree iden identified entified en d iin n thee AM A AMC, MC C, L LV V su summit, umm mit, orr iintramural ntrramural a sites al siitees between bettw these endocardial c iaal andd epicar cardia epicardial ardi ar d al sit sites. tes e . Echocard Echocardiography diogr grap gr a hy andd exercis ap exercise se stresss tes testing sti t ng or coronary coroo angiography hy de demo demonstrated mons mo nstr ns trat tr ated at ed no no evidence evid ev iden ence en ce ooff st stru structural ruct ru ctur ct ural ur al hheart eart ea rt ddisease isea is ease ea se iin n an anyy pa pati patients. tien ents en ts. The ts The ba base baseline se characteristics including the age, gender, left ventricular function, nature of the clinical arrhythmia, and 12-lead electrocardiogram during the VAs were recorded. The Institutional Review Board approved the study protocol, and all patients provided written, informed consent for the procedure. All antiarrhythmic drugs were discontinued for at least five half-lives prior to the study. Electrophysiological study For mapping and pacing, a quadripolar catheter was positioned via the right femoral vein at the His bundle region, and a deflectable decapolar catheter in the coronary sinus. The coronary sinus catheter was advanced into the GCV as far as possible until the proximal electrode pair recorded an

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earlier ventricular activation than the most distal electrode pair during VAs.6,7 Mapping and pacing were performed using a 7.5-French, 3.5-mm tip irrigated ablation catheter (Navistar ThermoCoolTM, Biosense Webster, Diamond Bar, CA, USA) introduced from the right femoral vein (for the RVOT and GCV) or right femoral artery (for the endocardial LVOT). During the procedures in the endocardial LVOT, intravenous heparin was administered to maintain an activated clotting time of > 300 seconds. Mapping and radiofrequency catheter ablation Activation mapping was performed in all cases to identify the earliest site ooff ve vent ventricular ntri ricu ulaar ac aactivation t ti during the VT VT oorr PV PVCs. VCs. Pace P ce mapping was performed Pa ed using the ddistal istall bbipolar ipolar electrodes at a pacing cycle le llength le e gth of 500 en 00 m mss andd aatt the m minimum innimu mu um sstimulus tiimul ulus ul u amplitude amp pliitudde required req quiredd for f r consistent fo conssisstee capture (up p to a m maximum axim ax imum mum ooutput utpu ut putt of 220 pu 0 mA an andd pu pulse uls lsee width widt wi dthh of 2.0 dt 2.00 ms). ms). The The pace pace map map score sco c r was determinedd as the number nuumb mber er of of le lleads ad ds with with h iidentical dent de nttic i al hheights eigh ei ghts gh ts of the the h R wave/depth wav ave/ e/de e/ dept de pthh of the pt the h S wavee (R/S) ratio match (12 represented a perfect R/S ratio match in all 12 leads), as well as the number of leads with fine notching matches in the 12-lead electrocardiogram as previously reported (perfect pace mapping was equal to 24 points)1. An excellent pace map was defined as a pace map with a score of > 20. When the earliest ventricular activation preceded the QRS onset by at least 20 ms and/or an excellent pace map was demonstrated in either the AMC or GCV, irrigated unipolar RF current was applied at this site. When there were no sites with such an early activation or excellent pace map in these regions, epicardial mapping via a subxiphoid approach was performed with irrigated ablation catheters to seek an earlier ventricular activation or excellent pace map on the LV

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epicardial surface as previously reported6,7,9. When a more suitable site for ablation was identified on the epicardial surface, irrigated unipolar RF current was applied at that site. If the first irrigated unipolar RF application from the AMC or GCV was unsuccessful, a second irrigated unipolar RF application was delivered at the site with the earliest ventricular activation on the opposing side (sequential unipolar ablation (SEQ-ABL)). If the sequential endocardial/epicardial ablation configuration was unsuccessful, irrigated unipolar RF current was simultaneously applied to the distal electrodess of two catheterss us usin using i two RF generators (StockertTM, BioSense Webster) at the same sites that were used ussed for for the the h sequential seq e u configuration ionn (si (s (simultaneous simullta taneoous unipolar ablation (SIM(SIM-ABL)) -ABL)) (Figur (Figure urre 1) 1). ). Irrigated RF currentt was delivered inn th the he power-control power-con ontrool mode dee startin starting ng at 20 20 W in in the the GCV G V and GC and 30 W at th the he A AMC M and MC and on the epicardial surfa ssurface ace c with witth irrigation irri ir riga gati ga tion ti on flow flo ow rates rate tess of 30 te 30 ml/min. ml/m ml / in /m n. The The RF power powe po werr was we was independently inde in depe de p nd pe nden e tlyy titrated up to 30 W and and 40 40 W, respectively. res espe spe p cttiv ivel ely. el y The y. The ssame am me setting s tt se ttin ingg was in was used used for for both bot o h sequential sequ se q ential aand simultaneous unipolar ablation. The goal of RF applications was to achieve a decrease in the impedance of 8 to 10 ȍDQGZLWKFDUHWDNHQWR limit the temperature to < 45°C as monitored from both RF generators. During the epicardial RFCA using transvenous and transpericardial approaches, simultaneous left coronary angiography was performed to ensure the location of the ablation catheter relative to the left coronary arteries and to detect evidence of thermal injury to the vessel. An RF application was never delivered within 5 mm of a coronary artery. When an acceleration or reduction in the frequency of the VT or PVCs was observed during the first 10 seconds at the AMC and 20 seconds in the GCV of the application after the RF power was titrated up to the maximum target, the RF delivery was continued for 30 to 60 seconds. Otherwise, the RF

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delivery was terminated, and the catheter was repositioned. The end-point of the catheter ablation procedure was the elimination and non-inducibility of VT or PVCs during an isoproterenol infusion (4 ȝg/min) and burst pacing from the right ventricle (to cycle lengths as short as 300 ms). Electrocardiographic analysis Simultaneous 12-lead electrocardiograms during VAs and pace mapping were recorded digitally at sweep speeds of 200 mm/s in all patients for offline analysis. The QRS morphologies including a bundle branch block pattern, axis, configuration in leads I and V6, were examined. In le lea lead ad I, the presence of an R wave was the main concern because the absence of R wav waves ves suggested sugg su gges gg essted d a VA V origin located ted ted d iin n the L LV V ffree ree wall. In lead V6, the main maiin concern w was as tthe he presence of S wav waves, which weree co considered onsidered too be be a characteristic chaaraacteristiic and d cconvenient onnveniient en nt electrocardiographic ellecctrrocarrdioographiic fi finding ind ndingg off AMC VAs5 probably a y because ably bec ecau ause au se tthe he S w waves avees in av i lea lead eadd V6 aare ree co cconsistent nsis ns i te is tent nt with wit ithh a right rig ight ht bundle bun undl dlle branch bran br anch an ch block bl pattern, usually u ually prese present sent ent iin n VA VAss with with h LV LV endocardial endo en dooca card rdia rd iall or ia orig origins. gin ns.. The QRS duration, maximal R wave amplitude in the inferior leads, and maximum deflection time in the precordial leads were measured with electronic calipers by 2 experienced investigators blinded to the site of origin. The maximum deflection time was measured from the QRS onset to the maximum deflection in each precordial lead. If there were discrepancies between those results, they were adjudicated by a third investigator. The maximum deflection index (MDI) was calculated by dividing the shortest time to the maximum deflection in any precordial lead by the QRS duration.10 The ratio of the Q wave amplitude in leads aVL to aVR (aVL/aVR) and that of the R wave amplitude in leads III to II (III/II) were also calculated.3 An MDI of > 0.54 was used as a predictor of an epicardial focal VA origin according to previous reports4,10.

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Follow up Follow-up after the procedure included clinic visits with 12-lead electrocardiograms and 24-hour Holter monitoring, and telephone calls to all patients and their referring physicians. All patients reporting symptoms underwent 24-hour Holter monitoring or event monitoring to document the cause of the symptoms. Successful RFCA was defined as no recurrence of VA during > 6 months of follow-up. Statistical analysis Continuous variables are expressed as the group mean ± 1SD or median an wit with itth th thee fi firs first rsst aand nd tthird quartiles (Q1 Q1 to Q Q1 Q3). 3)). C Comparisons omp m arisons of the continuous variables variables between betw tw weenn tthe he 2 groups were analyzed ann with the Student’s ude dent’s t-test or Ma Mann–Whitney ann–W Whitney U test test. t. The Th he ca categorical atego teego gorricaal variables varriaable l s expressed le exppreesse sed ass nnumbers u and percentages t es in tage n tthe he ddifferent ifffe fere rent re nt ggroups roup ro upps we were re ccompared ompa om paare redd wi with th a chi-square chi hi-sq squa sq uare ua re test tes estt and and Yates Yate Ya tees co ccorrection rrr if necessary. y The p-va y. p-values valu lu ues w were e e tw er two two-sided, o-ssid ided e , an and nd sstatistical t ti ta tist stic st iccal ssignificance ig gni n fi fica caancce wa w wass se sele selected lect le cted ct e at a valu ed value u of p 8 mm, and V-QRS at the presumable ablation site of < -30 msec, predicted the requirement for an SIM-ABL ablation with a sensitivity of 100% and 80%, specificity of 88.9% and 100%, positive predictive accuracy of 83.3% and 100%, and negative predictive accuracy of

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100% and 90%, respectively (Table 4).

Discussion Major findings In the past decade, advances in procedural techniques, and improved understanding of electrophysiological mechanisms, have allowed catheter ablation to cure most idiopathic VAs arising from the endocardium and epicardium.2–7,9 However, catheter ablation of idiopathic p VAs arising from intramural foci remains challenging.4 In addition, information ationn regarding rega re gard ga rdin rd ingg ho in how w tto predict the pres presence esen es e cee of en of intramural in ntr t amural foci and the bestt techniques tec echniques to treat att these these VAs is limited.. This study demonstrated ons ons nstr t ated that LV LVOT OT VAs Ass coul could ld uusually suallly y bee ccured ure redd bbyy RF re RFCA fr from rom m eithe either heer th the he en endocardial ndooc or epicardial a side al side. de. Ho de However, owe w veer, iin n a sign significant g ificant numb number m er er ooff case cases, es, s RF curr current r ent mu rr must ust bbee applied too both the endocardial r iall an rdia rd andd ep epic epicardial icar ardi ar dial al ssides ides id es tto o el elim eliminate imin inat atee LV at LVOT OT V VAs. As. Tw As Two Two-thirds o-thi third rdss of th thes these esee id es idio idiopathic iopa path pa thic icc intramural LVOT VAs were eliminated by irrigated unipolar RF applications sequentially delivered from the endocardial and epicardial sides while the remaining one-third were eliminated by irrigated unipolar RF applications simultaneously delivered from two different RF generators to the endocardial and epicardial sides. Intramural foci of LVOT VAs For mapping of VAs with a focal mechanism, seeking the earliest ventricular activation and/or an excellent pace map is the gold standard for identifying a successful ablation sites because an earlier activation and better pace map suggest a closer proximity to the VA origin.7 In 14 LVOT VAs in this study, the first RFCA delivered at the site of the earliest ventricular activation and/or best pace

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map on the endocardial or epicardial side was unsuccessful, and a subsequent RFCA delivered on the other side was required to eliminate the VAs. These findings suggested that these VAs originated from intramural foci in the LVOT. In several cases RF energy deliveries within the GCV were limited due to high impedances and temperatures, resulting in insufficient RF lesion formation. It is uncertain whether a higher RF current application from the GCV would have eliminated these VAs. However, because RFCA from the endocardial site with a later ventricular activation eliminated the VAs, an intramural focus was more likely than an an epicardial epi p cardial orr subendocardial focus. A presystolic local ventricular activation during VAss also als lsoo suggests sugg su ggges ests ts a close proximity to t the the VA A origin. o igin or in.7 In all intramural LVOT V in VAs As in this st study, tud u y, tthe he local ventricular activations du duri during r ng the VAs As pr preceded reccedeed the QR Q QRS S on onset nset by ggreater reat re ater at er th than han 100 m han msec. secc. In this h study, his stu t dy dy,, several sev ever eral er al idiopathic idi diop oppat athi hicc LVOT hi LVOT VA VAss were V w re ttransiently we rannsie ra nsie ient ntly nt ly y ssuppressed uppr up p es pr esse sedd du se duri during r ng RF R RFCA C delivered from fr eitherr the the endocardial e do en doca card rdia rd iall or eepicardial p caard pi rdia iaal side. siide de. Th This iss response res espo pons po nsse to tthe he aablation blat bl atio at i n mightt be characteristic of intramural LVOT VAs. It is known that tissue edema can occur around RF lesions.11 When the maximum temperature at the intramural focus is less than lethal or surrounding tissue edema affects the focus, the VA can be suppressed, but will recur. In one case in this study, RFCA from the AMC transiently suppressed the VAs and also attenuated the ventricular pre-potentials within the GCV. These findings suggested that RFCA from the endocardial and epicardial sides could affect intramural LVOT VA foci by the formation of tissue edema, resulting in transient suppression of the VAs. These findings also suggested that far-field ventricular pre-potentials recorded in the AMC and GCV during VAs might be characteristic of intramural LVOT VAs.

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According to the results of this study, the intramural LVOT VAs may be defined as in Table-5. Sequential versus simultaneous unipolar RF ablation In this study, unipolar RF current sequentially delivered from endocardial and epicardial sites sometimes failed to eliminate idiopathic intramural LVOT VAs. In those cases, unipolar RF current simultaneously delivered from the same endocardial and epicardial sites from separate RF generators could eliminate the VAs without any complications. These findings suggested that SIM-ABL delivered from the endocardial and epicardial sides might bee another op option ption for for R RFCA of LVOT VAs. There may be several possible mechanisms to explain thesee ffindings. indi in ding nggs. First, Fir irst st, st SIM-ABL can can in ca increa increase ase s th the he current density in the intramural intrram mural region. region onn. Increase Incr crease of current dens cr density can elevate the ti ttissue sssue temper temperature, ratturee, resu resulting ulting in a bet better tteer RF lesion les esio es ionn formation io form rm matio on inn the the intramural inntrramu m raal rregion. e Second, SIM-ABL M AB M-AB ABL L can c n increase ca incr in crea cr ease ea se tthe he "he "heat heatt lload" he oad" oa d bby y ha hhaving ving vi ngg 2 areas areas reeas ooff re resi resistive sist si stiv st ivee he iv heat heating atin at ingg oon in n bo bboth th h sides of the wall.. A conductive conduccti tive ve transfer tra rans n feer of ns o th tthee he heat at ffrom rom ro m both booth h sides sid ides ess of of the the wall th walll can can create crea cr eate ea te a greate greater e intramural damage during SIM-ABL. When RF energy is delivered simultaneously from the endocardial and epicardial sides, a deeper RF lesion from either side can be created more quickly. In one case in this study, the SIM-ABL terminated the sustained VT more quickly than the SEQ-ABL. This finding might support those possible mechanisms to explain the advantages of an SIM-ABL of idiopathic intramural LVOT VAs over an SEQ-ABL. In this study, an SIM-ABL was required when the distance between the endocardial and epicardial ablation sites was greater than 8mm. An experimental study revealed that the lesion depth created by an irrigated unipolar RFCA with an output of 30 W was 5 to 8 mm.12 Therefore, when intramural VA foci are located deeper than 5mm from both the endocardial and epicardial

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ablation sites, the RF lesion by an SEQ-ABL from either site may not eliminate the VA foci. In such a setting, the distance between the endocardial and epicardial ablation sites might be theoretically greater than 10 (5 x 2) mm. Therefore, the results of this study were considered reasonable for real world practice. The A/V amplitude ratio at the ablation site was significantly greater in the SEQ-ABL group than the SIM-ABL group, suggesting that VAs foci eliminated by SEQ-ABL might be located at a more basal side than those eliminated by SIM-ABL. These findings were consistent with the anatomical findings that the LV muscle cle thickness tape tapers pers rs toward to the LV base.13 The V-QRS at the successful ablation sites during VAs eliminated limina naate tedd byy SI S SIM-ABL M-AB AB was usually earlier r er than rlie th –30 –3 msec, m ec, while that during VAss eeliminated ms liminated bby y SE SEQ-ABL EQ-ABL was always llater than –30 msec. msec ms ec. When intramural inttraamu ural foci f ci are loc fo located ocated thee ddeeper eep eper ep er in inside nside de ven ventricular ntriccular m muscle, uscclee, itt may ma take the longer for the the h activation act ctiv i at iv atio ionn fr io from om ssuch uchh VA ffoci uc ocii to oc t aactivate ctiv ct ivat iv atee a ma at mass ss ooff ve vent ventricular ntri nt ricu ri cu ula larr mu musc muscle scle sc le llarg large arg enough to cause c a QR Q QRS S on onse onset. seet.. Wh When en n tthe he VV-QR V-QRS QR RS du duri during ring ng VA VAss of o earlier ear a li lier err than tha hann –30 –330 msec mse is recorded recorr in the AMC or GCV, SIM-ABL is very likely to be required to eliminate the idiopathic intramural LVOT VAs. Simultaneous unipolar RF ablation versus other ablation techniques Bipolar RF ablation using two ablation electrodes may have a disadvantage for the catheter ablation of idiopathic intramural LVOT VAs as compared with a simultaneous unipolar ablation. Bipolar ablation delivers the same current to both ablation electrodes, whether or not the electrodes are irrigated. This may be a significant restriction when a lower power setting is prudent because of the risk of a steam pop at either electrode location. In contrast, simultaneous unipolar ablation allows the power settings to be individually titrated at both ablation electrode locations. Thus,

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there is greater flexibility with simultaneous unipolar than with bipolar RF ablation, perhaps offering greater safety and efficacy. An intramural needle ablation catheter has been developed to create an intramural RF lesion.7,14 This catheter is not yet commercially available, but may be helpful to eliminate intramural LVOT VA foci as discussed in this study. The efficacy of this catheter for the intramural LVOT VAs should be tested in the future.

Conclusions This study rev revealed vea eale leed th that hat LV L LVOT VOT VAs likely originat originating tin ingg from intramura intramural al foci were eliminated d by irrigated RFCA FCA C from both botth thee endocardial endoocarddial an aand nd ep epicardial picarrdiall ssides. id ides des. These Th intramural in ntrram muraal LV L LVOT OT V VAs A were usually eliminated m atted minat d byy irrigated irrigaate ted unip unipolar polar RF current curr rren rr nt aapplied p lied ssequentially pp equentiaally from m th the he endocardial endocardii and epicardial ssides, ides id es, bu es butt re requ required quir qu ired ed d a ssimultaneous imul im ulta tane ta neou ne ouss de ou deli delivery live very ve ry of of ir irri irrigated riga gate ga tedd un te unip unipolar ipol olar ar R RF F current curr cu rren rr entt to bboth en o the endocardial and epicardial sides for their elimination when the distance between the endocardial and epicardial ablation sites was greater than 8 mm and the V-QRS during the VAs of earlier than –30 msec was recorded in the AMC or GCV. Conflict of Interest Disclosures: Drs. Kay, Plumb, and McElderry have participated in catheter research funded by Biosense-Webster and Irvine Biomedical. Dr. Kay has received honoraria from Medtronic, Boston Scientific, and St. Jude Medical. Dr. McElderry has received consulting fees from Boston Scientific, St. Jude Medical, and Biosense-Webster. The other authors report no conflicts. References: 1. Coggins DL, Lee RJ, Sweeney J, Chein WW, Van Hare G, Epstein L, Gonzalez R, Griffin JC, Lesh MD, Scheinman MM. Radiofrequency catheter ablation as a cure for idiopathic tachycardia of both left and right ventricular origin. J Am Coll Cardiol. 1994;23:1333-1341. 2. Yamada T, McElderry HT, Doppalapudi H, Murakami Y, Yoshida Y, Yoshida N, Okada T, 15 Downloaded from http://circep.ahajournals.org/ at New York University/ Medical Center--New York on February 12, 2015

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Tsuboi N, Inden Y, Murohara T, Epstein AE, Plumb VJ, Singh SP, Kay GN. Idiopathic ventricular arrhythmias originating from the aortic root: prevalence, electrocardiographic and electrophysiological characteristics, and results of the radiofrequency catheter ablation. J Am Coll Cardiol. 2008;52:139-147. 3. Ito S, Tada H, Naito S, Kurosaki K, Ueda M, Hoshizaki H, Miyamori I, Oshima S, Taniguchi K, Nogami A. Development and validation of an ECG algorithm for identifying the optimal ablation site for idiopathic ventricular outflow tract tachycardia. J Cardiovasc Electrophysiol. 2003;14:1280-1286. 4. Yokokawa M, Good E, Chugh A, Pelosi F Jr, Crawford T, Jongnarangsin K, Latchamsetty R, Oral H, Morady F, Bogun F. Intramural idiopathic ventricular arrhythmias originating in the intraventricular septum: mapping and ablation. Circ Arrhythm Electrophysiol. 2012;5:258-263. 5. Yamada T, Litovsky SH, Kay GN. The left ventricular ostium: an anatomic concept relevant to idiopathic ventricular arrhythmias. Circ Arrhythmia Electrophysiol. 2008;1:396-404. 6. Yamada T, McElderry HT, Doppalapudi H, Okada T, Murakami Y, Y Yoshida oshi os hida hi da Y, Y, Yoshida Yosh Yo shid sh idaa N, id N Inden Y, Murohara T, Plumb VJ, Kay GN. Idiopathic ventricular arrhythmiass origi originating gina gi nati na ting ti ng ffrom rom ro m th thee left ventricular summit: anatomic concepts relevant to ablation. Circ Arrhythm ythm Electrophysiol. E ec El ectr t op tr ophy hysi hy s ol si o. 2010;3:616-623. 6 623. 7. Yamada T T,, K Kay ay GN GN. N. Op Optima Optimal mall ab ma abla ablation ati tion on sstrategies trat tr a eg egie ies fo ie forr di different iffer fffer eren ent ty type types p s of pe o ven ventricular entr ntr tric i ul ic u ar ta ttachycardias. ach ch hyc y a Nat Rev Cardiol. ard ard rdiol. 2012;9:5 2012;9:512-525. 512-5 -55255. 8. Merino JL, J Pe Pein Peinado in nad adoo R, R Ramirez Ram mir irez L L,, Ec Echeverria Echeve verr ve rria rr ia II,, So Sobr Sobrino brin br inoo JA in JA. Ablation Abla Ab laati tion onn off idiopathic idi diop o at a hi hicc ve vventricular ntr tachycardiaa by bi bbipolar p laar radiofrequency po radiiof ofre r qu quen en ency ncy current cur u rent application app p li lica caati t on o bbetween e we et ween the h leftt ao he aort aortic ticc ssinus inus us and tthe left ventricle. Euro Europace. E opa pace ce. 20 ce 2000 2000;2:350-354. 000;2 2:3 350 50-3 -354 -3 544. 9. Yamada T. Transth Transthoracic thor th orac or acic ac ic eepicardial p ca pi card rdiaal ca rd cath catheter thet th etter aablation: b at bl atio ionn: iindications, io ndic nd icat ic atio at ions io n , techniques, ns teech chni n qu ni ques es,, and es an complications. ons Circ Ci J. J 20 2013;77:1672 2013 2013;77:1672-1680. 13;77 77:16 1672 72 1680 168 6800 10. Daniels DV, Lu YY, Morton JB, Santucci PA, Akar JG, Green A, Wilber DJ. Idiopathic epicardial left ventricular tachycardia originating remote from the sinus of Valsalva: electrophysiological characteristics, catheter ablation, and identification from the 12-lead electrocardiogram. Circulation. 2006;113:1659-1666. 11. Tanno K, Kobayashi Y, Kurano K, Kikushima S, Yazawa T, Baba T, Inoue S, Mukai H, Katagiri T. Histopathology of canine hearts subjected to catheter ablation using radiofrequency energy. Jpn Circ J. 1994;58:123-135. 12. Yokoyama K, Nakagawa H, Shah DC, Lambert H, Leo G, Aeby N, Ikeda A, Pitha JV, Sharma T, Lazzara R, Jackman WM. Novel contact force sensor incorporated in irrigated radiofrequency ablation catheter predicts lesion size and incidence of steam pop and thrombus. Circ Arrhythm Electrophysiol. 2008;1:354-362. 13. McAlpine WA. Heart and Coronary Arteries. New York: Springer-Verlag; 1975. 14. Sapp JL, Beeckler C, Pike R, Parkash R, Gray CJ, Zeppenfeld K, Kuriachan V, Stevenson WG. Initial human feasibility of infusion needle catheter ablation for refractory ventricular tachycardia. Circulation. 2013;128:2289-2295.

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DOI: 10.1161/CIRCEP.114.002259

Table 1: The results of mapping and ablation

Patient No.

Ablation technique

1

V-QRS (ms)

Pace map score

The sequence of the ablation

Endo

Epi

Endo

Epi

Seq

-25

-18 (-30)*

N/A

N/A

(QGRĺ(SL

2

Seq

-19

-21

19

N/A

Epi /( ĺ(QGR

3

Seq

-17

-21

17

N/A

Epi 76 ĺ(QGR

4

Seq

-16

-23

21

N/A

Epi /( ĺ(QGR

5

Seq

-13

-20

17

20

(SLĺ(QGR (SLĺ (S Lĺ(Q Lĺ (QGR (Q GR GR

6

Seq Seq

-25

-25

222

N/A

(QGRĺ(SL

7

Seq

-1 -11 11

--22 -2 2

221 1

222

Ep Epi pi 76 ĺ(QGR 76 7 6 ĺ( 6 ĺ(QG QG

8

Seq S q Se

-188 -1

-255

1188

22

(SLĺ(QGR ( (S Lĺ(Q Lĺ (QGRR (Q

9

S q Se Seq

-200 -2

-177 -1

9

5

(Q QGR GRĺ( ĺ(SL ĺ( (QGRĺ(SL

10

Sim Si m

-42 -442

-37 -337

13

100

Endo E do En d 7 76 ĺ(SLĺ6LP 76 ĺ(SLĺ 76 6 ĺ( (SL SLĺ

11

Sim

-30

-35

N/A

N/A

Epi 76 ĺ(QGRĺ6LP

12

Sim

N/A

N/A

20

22

(SLĺ(QGRĺ6LP

13

Sim

-24

-15

7

16

(QGRĺ(SLĺ6LP

14

Sim

-22

-31

18

23

(SLĺ(QGRĺ6LP

Endo=endocardial; Epi=epicardial; LE=limited delivery of radiofrequency energy; N/A=not available; Seq=sequential; Sim=simultaneous; TS=transient suppression; V-QRS=the local ventricular activation time relative to the QRS onset. *; The activation time was -18 msec at baseline, but it changed to -30 msec together with the change in the QRS morphology after the endocardial ablation.

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DOI: 10.1161/CIRCEP.114.002259

Table 2: The basic demographics and clinical characteristics

Sequential (n=9)

Simultaneous (n=5)

p-value

Age (years)

57±11

60±12

0.642

Male, n (%)

5 (56)

1 (20)

0.198

58.1±10.1

60.2±8.1

0.842

2 (22)

1 (20)

0.923

LVEF (%) Tachycardia-induced CM, n (%)

00.834 0. 8344 83

Clinical arrhythmia, n (%) Frequent PVCs

4 (44)

3 (60)

a ned ain e VT Nonsustained

3 (33))

1 (2 (20)

Sustainedd VT

(222) 2 (22)

(220) 1 (20)

Data are expressed CM=cardiomyopathy; xpressed xpress ssed ss ed aass th the he me mean ean a ±S SD D or o nnumber umbe um berr with be wiith h the the percentage. perrce cent ntag nt ag ge. C CM=cardiomyopathy M ca M= card rdio rd i my io myop opat op athy LVEF=left ventricular VT=ventricular vent n ri nt r cu cula laar ejection e ec ej e ti t on ffraction; ract ra ctio ct io on; PVC=premature PVC VC=p =prema =p m tu ma ure vventricular en ntr tric icul ic ular ul a ccontraction; ar onntrac trrac acti tiion o ; VT=ventr VT=v VT =ventr =v tachycardia. a.

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DOI: 10.1161/CIRCEP.114.002259

Table 3: The comparison of the electrocardiographic and electrophysiological parameters

Total QRS duration of the VA (msec)

Sequential (n=9)

Simultaneous (n=5)

p-value

160±22

169±24

0.487

QRS morphology, n (%) LBBB+LIA

0.303 1 (11)

0 (0)

LBBB+RIA

0 (0)

1 (20)

RBBB+RIA

8 (89)

4 ((80)

Precordial transition, n (%)

0.127 8 ((89))

((4 2 (40)

0

( 1 (20)

(1 11) 1 (11)

( 2 (40)

m ) mV) R wave amplitude in the inferior leads (mV)

1.24 24±0 24 ±0.332 ±0 1.24±0.32

1 422± 1. 1.42±0.30

0.332

R wave amplitude ratio in leads III to II

1.04 1. 044±0 ±0.119 1.04±0.19

1.008± 1. 1.08±0.09

0.618

V VR Q wave amplitude ratio in leads aVL to aVR

1.22 1. 22±0 22 ±0.4 ±0 .444 .4 1.22±0.44

1.15± ± 1.15±0.09

0.742

Maximum deflection index

0.48±0.06 4 (44)

0.50±0.06 0 (0)

0.435 0.078

-20.4±5.4

-33.0±7.5

0.006

M=16, Q1 to Q3=11 to 35

M=21, Q1 to Q3=14.5 to 34

0.711

M=0.168, Q1 to Q3=0.095 to 0.38 4.1±0.8

M=0.025, Q1 to Q3=0.015 to 0.046 5.4±1.5

0.006 0.054

5.8±2.0

11.4±2.9

0.001

< V1 V1 V2-V3

S wave in lead V6 (%), n (%) V-QRS (msec) Ablation site His bundle region A/V amplitude ratio at the ablation site Number of RF applications Distance between the endocardial and epicardial ablation sites (mm)

Data are expressed as the mean ± SD, number with the percentage, or median with the first and third quartiles (Q1 to Q3). A/V=atrial to ventricular electrogram; LBBB=left bundle branch block; LIA=left inferior axis; RBBB=right bundle branch block; RIA=right inferior axis; RF=radiofrequency; VA=ventricular arrhythmia; V-QRS=the local ventricular activation time relative to the QRS onset.

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DOI: 10.1161/CIRCEP.114.002259

Table 4: Sensitivity, specificity, and positive and negative predictive accuracies of the parameters for the requirement of the simultaneous ablation

Sensitivity

Specificity

PPV

NPV

The distance between the ablation sites > 8 mm

100%

88.9%

83.3%

100%

V-QRS < -30 msec

80%

100%

100%

90%

NPV=negative predictive value; PPV=positive predictive value

Table 5: Defi Definition D fini fi niti ni t on of of the th he intramural inttraamur ural ur al LVOT LVO VOT T VAs VA

Major criteria rit rit iteriia 1. The local ventricular activation < -10 msec on both the endocardial and epicardial sides. 2. The earliest local ventricular activation < -20 msec on the endocardial or epicardial side. 3. Unsuccessful radiofrequency ablation at the site of the earliest local ventricular activation and/or best pace map, and successful sequential or simultaneous ablation at the sites directly across the wall. Minor criteria 1. Transient suppression of VAs during radiofrequency ablation delivered from either the endocardial or epicardial side. 2. Far-field ventricular pre-potentials recorded in the endocardial and epicardial sites during VAs.

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DOI: 10.1161/CIRCEP.114.002259

Figure Legends:

Figure 1: Fluoroscopic images exhibiting the ablation sites. ABL=the ablation catheter; CS=coronary sinus; Endo=the endocardial ablation catheter; Epi=the epicardial ablation catheter positioned within the great cardiac vein (GCV); HB=His bundle; LAO=left anterior oblique view; RAO=right anterior oblique view.

Figure 2: A flow diagram exhibiting the results of the mapping and catheter athete terr ab abla ablation. lati tion onn. ABL=ablation; t on; tion onn; AM AMC= AMC=aorto-mitral C ao C= ort r o-mitral continuity; N=number; N=num umber; V-QR V-QRS=the RS= S th he local ventricular activation tim ttime imee relative too thee Q im QRS RS S onset. onset.

Figure 3: Electrocar Electrocardiograms rdi diog oggra rams ms exh exhibiting xhib xh ibit ib ittin ng a premature prem pr emat em a ur at uree ve vventricular ntri nt r cu ri c la larr co ccontraction ntra nt r ct ra ctio ionn (PVC) io ( VC (P VC) and pa pace maps obtained by pacing from the AMC and GCV (left panels) and cardiac tracings exhibiting the successful ablation site in the AMC (right panel). Although the pace map was better and ventricular activation time during the PVC was earlier within the GCV (arrowheads) than the AMC, the first ablation from the GCV failed, and the subsequent ablation from the AMC successfully eliminated the PVCs. ABL=the ablation catheter positioned in the AMC; CS 1 to 5=the first (most distal) to fifth (most proximal) electrode pairs of the CS catheter; X d, p=the distal and proximal electrode pairs of the relevant catheter. The other abbreviations are as in the previous figures.

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DOI: 10.1161/CIRCEP.114.002259

Figure 4: A: Electrocardiograms exhibiting the ventricular tachycardia (left panel) and cardiac tracings exhibiting the successful ablation sites (right panel). Note that the patient was also in atrial flutter. A far-field ventricular pre-potential was recorded from the ablation catheter positioned within the GCV (ABL-d). B: Cardiac tracings exhibiting the effective (upper panel) and successful ablations (lower panel). An effective ablation was achieved by a radiofrequency ablation within the GCV, and the successful ablation was achieved by a simultaneous unipolar radiofrequency ablation from the GCV and AMC. Note that the ventricular tachycardia ia terminated more ree qquickly u during the successful ablation than the effective ablation. ABL (abl)=the he ablation abl bllat atio ionn catheter cath ca t etter th e positioned within wit ithi hin the hi th he GCV GC CV (AMC). The other abbreviations abbreviiations are ass in th the previous figures.

Figure 5: Card C Cardiac dia iacc tracings trac tr acin ac ings in g exhibiting gs exhi ex hibi hi biti bi tiing the thee change cha hang ngge inn the the ventricular ven entr tric tr icul cul ular arr ppre-potential re-ppot re oten en nti tial all rrecorded ecor ec orde or ded w de within the GCV (arrowheads) a arrowhead ds) before bef efor o e an or and nd af afte after terr th te thee ab abla ablation lati la tiion fr ffrom o tthe om hee A AMC. MC C. T The he aablation bllat a io ionn fr ffrom om the A AMC suppressed the PVCs and also attenuated the ventricular pre-potential. ABL=the ablation catheter positioned in the AMC. The other abbreviations are as in the previous figures.

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Simultaneous

Sequential

Epi GCV HB

Endo

ABL

LAO CS

HB H B

Epi

GCV Endo

RAO CS

ABL HB

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HB

Study patients N=64 Earlier activation GCV N=36 < -20 msec N=22

AMC N=28 > -20 msec N=14

V-QRS in the GCV

Success N=23

Transpericardial mapping Earliest E Ea rliestt activation rl activ iv vattion n

GCV V N=2

N=24 ABL in the GCV

Failure N=9

ABL in the AMC Failure N=5

Success S u N=3

Accessible Ac A cce cess ssib ible ib l aarea le reaa re N=6

IInaccessible In acce ac cess ssib ible ib le aare area re N=6

Successful ABL N=6

Failed ABL N=6

ABL in the GCV

Failure N=2

Success N=15 Success N=6

ABL in the AMC

Failure N=3

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Simultaneous ABL N=5 Success N=5

PVC AMC GCV I II III aVR aVL aVF V1 V2 V3 V4 V5 V6

I II III aVR aVL aVF V1 V22 V V V33 V44 V V55 V V6 ABLp ABLd HBp HBd CS 5 CS 4 CS 3 1 mV CS 2 Downloaded from http://circep.ahajournals.org/ at New York University/ Medical 1 Center--New York on February 12, 2015 200 ms CS

200 ms

V-QRS = –11 ms

V-QRS = –22 ms

A. I

I

II

aVF V1

III aVR

V6

aVL

ABL-p p abl-p l-p l-

aVF V1

L-d d ABL-d

V-QRS = –35 ms

abl-d

V2

V-QRS = –30 ms

CS 5 V3

CS 4

V4

CS 3

V5 1 mV

V6

CS 2 200 ms

CS 1

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200 ms

B. I aVF V1 V6

11.0 sec

ABL-p ABL-d CSp CSd I aVF V1 V6 ABL-p abl-p ABL-d abl-d CSp CSd

3.5 sec

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I II III aVR aVL aVF V1 V2 V3 V4 V5 V6 ABLp ABLd HBp HBd CS 5 CS 4 CS 3 CS 2 CS 1

200 ms

I II III aVR aVL aVF

V V1 V2 V2 V3 V3 V4 V4 V5 V6 V-QRS = –42 ms HBp HBd CS 5 CS 4 CS 3 CS 2 CS 1 Downloaded from http://circep.ahajournals.org/ at New York University/ Medical Center--New York on February 12, 2015

200 ms

Radiofrequency Catheter Ablation of Idiopathic Ventricular Arrhythmias Originating from Intramural Foci in the Left Ventricular Outflow Tract; Efficacy of Sequential vs. Simultaneous Unipolar Catheter Ablation Takumi Yamada, William R. Maddox, H. Thomas McElderry, Harish Doppalapudi, Vance J. Plumb and G. Neal Kay Circ Arrhythm Electrophysiol. published online January 30, 2015; Circulation: Arrhythmia and Electrophysiology is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2015 American Heart Association, Inc. All rights reserved. Print ISSN: 1941-3149. Online ISSN: 1941-3084

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