high-resolution mapping of scar-related atrial...

32
DOI: 10.1161/CIRCEP.114.002737 1 High-Resolution Mapping of Scar-Related Atrial Arrhythmias Using Smaller Electrodes with Closer Interelectrode Spacing Running title: Anter et al.; High resolution scar mapping Elad Anter, MD; Cory M. Tschabrunn, CEPS; Mark E. Josephson, MD Harvard-Thorndike Electrophysiology Institute, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA Correspondence: Elad Anter, MD Harvard-Thorndike Electrophysiology Institute Beth Israel Deaconess Medical Center 185 Pilgrim Rd, Baker 4 Boston, MA 02215 Tel: 617-632-9209 Fax: 617-632-7620 E-mail: [email protected] Journal Subject Codes: [22] Ablation/ICD/surgery, [106] Electrophysiology, [124] Cardiovascular imaging agents/techniques osephson, MD H d Th dik El t h il I tit t C di l Di i i Ha a arv rv rvar ar ard d d -T -T -Tho o o orn r rn r dike Electrophysiology I Ins ns nstitute, Cardiova a a asc s s scular Division, Departme e en nt o o o of Me Me Me Medi di di dic c cine ne e e , , , B B Bet th I Isr r rael l D Deac ac ac a on n n ne e ess Me M M di di dica al Ce Ce Ce C nter er er & & & Ha Ha Ha H rvar ar ar ard d d d Me M M M di di di d ca ca ca cal l l l Sc Sc Scho ho hool ol l, , , Bo Bo Bo Bost st st s on on on on, MA MA MA MA by guest on June 23, 2018 http://circep.ahajournals.org/ Downloaded from

Upload: truongdiep

Post on 15-May-2018

221 views

Category:

Documents


2 download

TRANSCRIPT

DOI: 10.1161/CIRCEP.114.002737

1

High-Resolution Mapping of Scar-Related Atrial Arrhythmias Using Smaller

Electrodes with Closer Interelectrode Spacing

Running title: Anter et al.; High resolution scar mapping

Elad Anter, MD; Cory M. Tschabrunn, CEPS; Mark E. Josephson, MD

Harvard-Thorndike Electrophysiology Institute, Cardiovascular Division,

Department of Medicine, Beth Israel Deaconess Medical Center &

Harvard Medical School, Boston, MA

Correspondence:

Elad Anter, MD

Harvard-Thorndike Electrophysiology Institute

Beth Israel Deaconess Medical Center

185 Pilgrim Rd, Baker 4

Boston, MA 02215

Tel: 617-632-9209

Fax: 617-632-7620

E-mail: [email protected]

Journal Subject Codes: [22] Ablation/ICD/surgery, [106] Electrophysiology, [124] Cardiovascular imaging agents/techniques

osephson, MD

H d Th dik El t h i l I tit t C di l Di i iHaaarvrvrvarararddd-T-T-Thoooornrrnr dike Electrophysiology IInsnsnstitute, Cardiovaaaascssscular Division,

Departmeeennt oooof MeMeMeMedidididicccineneee,,, BBBetth IIsrrraell DDeacacaca onnnneeess MeMM dididicaal CeCeCeC ntererer &&&

HaHaHaH rvararararddd d MeMMM dididid cacacacal lll ScScSchohohoololl,,, BoBoBoBostststs onononon, MAMAMAMA

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

2

Abstract:

Background - The resolution of mapping is influenced by electrode size and interelectrode

spacing. Smaller electrodes with closer interelectrode spacing may improve mapping resolution,

particularly in scar. The aims of this study were to establish normal electrogram criteria in the

atria for both 3.5mm electrode tip linear catheters (Thermocool®) and 1mm multielectrode-

mapping catheters (Pentaray®) and to compare their mapping resolution in scar-related atrial

arrhythmias.

Methods and Results - Normal voltage amplitude cutoffs for both catheters were validated in 10

patients with structurally normal atria. In 20 additional patients with scar-related atrial

arrhythmias, similar sequential mapping with both catheters was performed. Normal bipolar

voltage amplitude was similar between 3.5mm and 1mm electrode catheters with a 5th percentile

of 0.48mV and 0.52mV, respectively (p=0.65). In patients with scar-related atrial arrhythmias,

the total area of bipolar voltage <0.5mV measured using 1mm electrode catheters was smaller

than that measured using 3.5mm catheter (14.7cm2 vs 20.4cm2; p=0.02). The mean bipolar

voltage amplitude in this area of low voltage was significantly higher with 1mm electrode

catheters (0.28mV and 0.17mV, p=0.01). Importantly, 54.4% of all low voltage data points

recorded with 1mm electrode catheter had distinct electrograms that allowed annotation of local

activation time compared with only 21.4% with 3.5mm electrode tip catheters (p=0.01).

Overdrive pacing with capture of the tachycardia from within the area of low voltage was more

frequent with 1mm electrode catheters (66.7 vs 33.4; p=0.01).

Conclusions - Mapping with small closely spaced electrode catheters can improve mapping

resolution within areas of low voltage.

Key words: ablation, mapping, electrophysiology, arrhythmia

ororrrmemememed.d.d.d. NNNNorororormamamamal lll bbbbipopopopolalaaa

heters s ss wiwiwiwithththth aaaa 5555thth pepepepercr

m

ea of bipolar voltage <0.5mV measured using 1mm electrode catheters was smal

m r

m

0.28mV and 0.17mV, p=0.01). Importantly, 54.4% of all low voltage data points

with 1mm electrode catheter had distinct electrograms that allowed annotation of

annnnd d d 0.000 525222mVmmV, rererer spectively (p=0.65). In papapatit ents with scccar-rerererelall ted atrial arrhythm

eeeae oooof bipolar rr vovov ltagagagagee ee <0<0<0.5.5.5. mVmVmVV mmmeaasurereed uusiing g g g 1m1m1m1mmm m elelelleeectrtrrododo e cacacacaththththeteteterererrs wawawaasss s smsmsmsmal

measasasuruu ed usisisis ngg 33.5mmmm cccatatathehhh teeer rrr ((((14.777cmmm2 vs 20202020.4cmccmc 2; pp=p=p 0.0202). TTTThehhh mmmmeeeann bbipoolllar

mplitudududde in tttthihh s ararareaeaea of low www voltaggge wawawaw s sisisisigngngnnificananantltt y yy highgg ererere with 1m1m11mm mmm electrode

0.28m888 VV V andd d 000.17777mVVV, , p=pp 00.0 0001).).). IIImppportantlylyly,, 5545 44.44%%%% offff aallllllll lllowwww v lolltagegg ddddata aaa popopopoints

wwitith h 1m1mm m elelellecectrtrt ododdde e caacaththththeteterer hhhhaddada dddisiisi titititincnnct t t ellellecectrtrtt ogograaaramsms tthahhah t t tt alallllolol wewed dd d anannonotatat titionon oof f by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

3

Introduction

Atrial fibrillation (AF) ablation is an acceptable therapeutic option for patients with symptomatic

AF refractory to medications.1 Pulmonary vein isolation (PVI) is the cornerstone of the procedure

and is associated with a reasonable clinical outcome in patients with paroxysmal AF. However, in

patients with persistent AF, PVI is less effective and additional substrate ablation is frequently

performed.2, 3 This approach often results in the development of post-ablation, scar-related,

organized atrial tachyarrhythmias. 4-6

The mechanism of these arrhythmias is usually reentry involving preexisting or iatrogenic

ablation-related scar tissue.7, 8 These circuits are typically challenging to map because of significant

scar coupled with fractionated and multicomponent electrograms, limiting local time annotation. In

addition, entrainment and post-pacing interval mapping techniques may also be difficult to perform

and interpret due to high output pacing and/or lack of capture in these areas of low voltage.

The standard catheter for mapping these arrhythmias is a linear catheter with a 3.5mm

distal electrode separated by 2mm from a proximal 2mm electrode, resulting in a center-to-center

interelectrode spacing of 4.75mm. As such, each bipolar electrogram represents an underlying

tissue diameter ranging from 3.5mm to 7.5mm, depending on the angle of incidence (from

perpendicular to parallel to the tissue, respectively). Catheters with 1mm electrodes, 2mm

interelectrode spacing, and 3mm center-to-center interelectrode spacing record electrograms

from a significantly smaller underlying tissue diameter, ranging from 1mm to 4.0mm (also

dependent on catheter orientation relative to the surface). These catheters may have advantages

for mapping scar-related arrhythmias, including: 1) higher mapping resolution that can identify

heterogeneity within the area of low voltage, localizing “channels” of surviving bundles; 2)

smaller electrodes with closer interelectrode spacing are subjected to less signal averaging and

gg ppreexistingg or iatrtrrrogogogo e

map p bebbbecacaususee ofof ssigigigignnnini

ed with fractionated and multicomponent electrograms, limiting local time annotatio

n r

e

e m

rode separated b 2mm from a pro imal 2mm electrode res lting in a center to

ed wiwiiwithththth fffrararaactctctionanananated and multicomponent eeelelell cctrograms, limi itininini gg g local time annotatio

ntttrt aaaia nment andd pposttt-ppaciiingnn inttnteervavval mappppinngg teechchchc nininiiqquesss mmmayy aalsooo bbbe didiiifffffficculult tooo ppper

et dueeee tooto hhhhigigh hhh outttptp ttut pacinnngggg and/ororrr llllacacckkkk offf capaptututturererere inininin theheheh seseses areas offf f lololoow voltltltage.

e standddarddd catatathehhetet r ffof r mapppppping gg thhhese ar hhrhytytythmhh iiias iisi a llinininear rr ccca hththeter wiiti h hh aaa 3.33 5m

r dod ttedd bb 22 ff iim lal 22 lle tct dde ltltiin iin tte tto

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

4

cancellation effects, and may thus record higher bipolar voltage amplitude with shorter

electrogram duration, allowing more accurate time annotation; 3) pacing with capture at lower

output due to increased electrical density.

The aims of this study were to: 1) establish normal voltage amplitude cutoffs in the atria

for both 3.5mm electrode tip catheters and 1mm multielectrode-mapping catheters; 2) compare

their mapping resolution in scar-related organized atrial tachyarrhythmias (AT).

Methods

Patients

This study included 30 patients. In order to define normal bipolar electrograms in the atria

(voltage amplitude and electrogram duration), we studied 10 patients with paroxysmal AF

undergoing index PVI. In attempt to include only patients with structurally normal atria, eligible

patients were 65 year-old, had paroxysmal AF with arrhythmia duration

valvular disease, and all underwent cardiac magnetic resonance imaging (CMR) that

demonstrated non-scarred atria as evidenced by absence of late gadolinium enhancement. In

order to compare mapping resolution in scar, 20 additional patients with history of prior catheter

and / or surgical ablation and recurrent persistent atrial arrhythmias were also studied. Patients

were enrolled prospectively, however data was analyzed retrospective at the end of the study.

The institutional review board of Beth Israel Deaconess Medical Center approved the study

protocol and patients provided written informed consent prior to the clinical procedure.

Mapping Protocol

All procedures were performed under general anesthesia with the use of jet ventilation.

Electroanatomic mapping was performed with Carto 3 mapping system (Carto 3 ® system,

Biosense Webster). The linear mapping catheter was an open irrigated mapping/ablation catheter

included 30 patients. In order to define normal bipolar electrograms in the atria

m

g index PVI. In attempt to include only patients with structurally normal atria, eli

e

sease, and all underwent cardiac magnetic resonance imaging (CMR) th

incluuudededed d d 303030 ppatataatients. In order to define noonormrr al bipolar electctctctror grams in the atria

mmmpm lilililitude and eeeleectttrorrr grgrgrgraaaam m m m dddudurarararatiitionoon), wweee stududieeedd dd 010100 pppatattieeentnts s wwithhh ppparoxoxoxxysysysmamamaallll AFAFAFA

g indndnddexexexex PPPPVIVIVIVI. InInInI aaaattttttt ememememptpp ttto ooo inininnclclclcluddddeeee onononnlylylyy ppppaata ieieieentntntnts s wiwiwiwithhhh ssstrtrtrt ucucucuctututurararaalll y yy nonononormrmrmrmalalala atrtrtrriaiaiaa,,, elelele i

ere 6565656 yyyeaeaearrr-o-o-oldldldld,,,, hahahad dd papaparororoxyxxyxysmmmmalalal AAAFF F F wiwiiiththth aaarrrrrrr hyhyhyhythththhmimimiaa a a dudududurararatititiononoon

seseasase,e, aandnddd aallllllll uundndddere wewwentnt ccara didididiaacac maggagneetititit c c reesosonaaaancce e imiimi agagininii g g (C(C(C(CMRMRMRMR) )) ) ththththatat by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

5

(Thermocool®, Biosense Webster, Diamond Bar, CA – “linear”) and the multielectrode mapping

catheter was a 20-pole steerable mapping catheter arranged in 5 soft radiating spines covering a

diameter of 3.5cm (Pentaray®, Biosense Webster; Diamond Bar; interelectrode spacing 2-6-2mm

- “multielectrode-mapping ”). The linear catheter has a 3.5mm distal electrode separated by 2mm

from a 2mm proximal electrode, resulting in 4.75mm center-to-center spacing. The

multielectrode-mapping catheter has 1mm electrodes with interelectrode spacing of either 2 or 6

mm. For the purpose of this study, we recorded bipolar pairs with interelectrode spacing of 2mm

resulting in 3mm center-to-center interelectrode spacing. In order to examine the effect of

interelectrode spacing on mapping resolution in scar, a subset of 10 patients with atrial scar

underwent similar mapping with both the linear and the multielectrode-mapping catheters.

However, in addition, during mapping with the multielectrode-mapping catheter, electrogram

were recorded using both bipolar pairs separated by 2 and 6mm. All bipolar electrograms were

filtered between 30 and 500 Hz. Long sheaths were used to support both mapping catheters in

the right and left atrium.

Mapping of the substrate

Mapping of the chamber (right and left atrium) was performed in sinus rhythm. Initial mapping

was performed with the linear mapping catheter in point by point fashion. In all 10 patients with

structurally normal atria in whom normal values were established, the linear mapping catheter

was Thermocool Smart Touch® that allows force sensing and confirmation of tissue contact.

Electrograms were accepted only within a contact force range between 5-25 grams. Thermocool

Smart Touch® was also used in 11 of the 20 patients with scar-related ATs, using similar criteria.

The remaining 9 patients were mapped before contact force catheters were approved for

commercial use in the US, and therefore an ablation catheter without contact force sensing was

xamine the effect oooof f ff

atientttts s wiiiwithththth aattrtrt iiaiai l l scscscscara

i a

d w

w s

nd left atri m

simimiimilalalal rrr mamamam ppppinining with both the linear annnd ddd ththe multielectctc rodededed ---m- apping catheters.

innn n aaada dition, duuriing mmappipipiing wwithhh tthe mmmulttieelectctctrorororodedded -mmaaappingng ccacc ttht eteeree , elleectrogogogra

ded ususuusinininingggg boththth bbbbipipii lllolar paiaiaiirsrsrsrs separrrratatatateddeded bbby y 222 andddd 6m6m6m6 mmmm. AlAlAlA l l bibibipolar elelelelectrograms w

ween 333000 and dd 505055 000 0 HHHz. LLLonggg shehhh athhsh were useddd tto suppppppororrrt t bobobothththh mappppipipinggg ccccatatatatheheheheters

dd lleftft ttrii

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

6

used. To ensure detailed and uniform mapping of the entire chamber, we set the mapping filling

10mm (allowing interpolation between points to be as a requirement for a

complete map. In addition, each map made with either the linear or the multielectrode-mapping

catheters was registered with CMR whenever imaging was available. After completion of the

electroanatomical map with the linear catheter, a new shell of the chamber was created with the

multielectrode-mapping catheter

the multielectrode mapping catheter does not have contact force sensing technology, we used an

internal point filter software available on the mapping system to limit data acquisition to within

5mm from the original shell made with contract force technology. This algorithm, although not

an equivalent to tissue contact, can potentially reduce mapping of cavitary structures. In the

group of patients with scar-related ATs, similar sequential mapping with both catheters was

performed in sinus rhythm in order to characterize the substrate and particularly the zone of low

voltage and scar. Mapping of one or both atria was performed based on the electrocardiographic

characteristics of the AT.

Mapping of the arrhythmia

In the group of patients with scar related atrial arrhythmias, 14 patients had 26 ATs while 6 had

AF. We attempted to map all ATs with both catheters. Electrograms were selected for local time

annotation if their bipolar voltage amplitude was >0.06mV (2-fold higher than the noise level in

our lab) and had distinct and reproducible near-field potentials. Once activation maps were

completed and the putative circuit identified, overdrive pacing was performed in order to entrain

the tachycardia and further characterize the circuit. Entrainment pacing was performed at a cycle

length 10-25 msec faster than the tachycardia. The pacing site was considered part of the circuit

if the post-pacing interval measured from the stimulation artifact to the return atrial electrogram

data acqquisition ttoooo wiwww

s algogoririiiththththm,m aaltltltlthohooougugugughh

e h

a s

in sinus rhythm in order to characterize the substrate and particularly the zone o

d a

tics of the AT

ent t t t totototo ttisisisi susususuee coooonntnn act, can potentially redddduucu ee mapping off cavivivitary structures. In th

attttieeeents with sccarr-reelaated dd AATAA s, simmmilarr sssequeuentiaiaiaiall mammam ppppinnng wwitth bbbbooth ccacc thtt eteters wwwa

in sinininnususus rrhhyhyththththm iniii orddder tttoooo hhcharacacccteteteteriririze ttthhhe sububububststs rarararattetete aaandndndn ppartittt culalalalarlrlrlrly y thhhhe zone o

d scar. MMaM ppppppinininng gg ffof one or bbobb thhhh at iriia was pepp rfffformed dd babb seseeedd d onnn thehhh elelll ctrocacaaardrdrdr iiioi grgg a

ttiic fof tthhe AATT

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

7

on the ablation catheter was within 25 msec of the tachycardia cycle length (TCL). Pacing at

multiple sites was performed with both the linear and multielectrode-mapping catheters.

Comparison of pacing output threshold

Overdrive pacing of an arrhythmia is often performed in attempt to determine its mechanism

and/or localize its origin. However, pacing with capture is not always possible, particularly in

areas of low voltage and scar. In addition, pacing at high output can result in significant artifact

precluding its interpretation. As catheters with smaller electrodes and closer interelectrode

spacing have higher current density, we hypothesized they will have lower pacing threshold. We

compared pacing output threshold between the linear and the multielectrode-mapping catheters

during tachycardia. Pacing with the multielectrode-mapping catheter was performed after

completion of the activation map and at multiple atrial sites. Each pacing site was tagged on the

electroanatomical shell and pacing output threshold was recorded. Pacing was then repeated with

the linear catheter at similar anatomical sites and cycle length. Pacing sites were considered

similar if they were within 5mm from one another. Titration of pacing output was performed by

changing the pacing output strength within a range from 2.0 to 20 mA at a constant pulse

duration of 2.0 msec. Failure to capture was defined as lack of capture at 20mA at 2ms.

Radiofrequency ablation

Ablation of ATs was guided by activation and/or entrainment mapping. In reentrant circuits,

radiofrequency ablation was performed in attempt to disrupt the circuit with a line applied

between two anatomical barriers (i.e., mitral annulus to left inferior pulmonary vein in mitral

annular flutter) or at the earliest activation site of focal non-reentrant tachycardias. Ablation was

performed using the 3.5mm open irrigated catheter with energy of 20-40W. Energy was titrated

to achieve a 10-15 Ohms impedance decrease. If the AT terminated during radiofrequency

ower pap cingg thresshohohoholdl

ctrodededd -m-mapap iipipingngg cacaaaththththe

h

n n

t

c d

he ere ithin 5mm from one another Titration of pacing o tp t as performe

hyccccarararardidididiaa. PPPPaacinnngg gg with the multielectrode-m-m-maapping cathetee er wwwwas performed after

n offf f the activattioon mmmap ananand atttt muuulltiplle atrriaial siiiiteteeessss.... EEachchch paccinng sisisite wwwwasss tttagggededed on

tomiiicacaccallll shshshshell a ddndd ppacinii g ouououutptptput thrhrhrhreeese hohohoh ldddd was rerererecococordrdrdrdedddd. PPPa iicing wasasasas ttthen repe ttate

cathehhh ter at simimimiilili ar anatomicii al siiites andd d cyyy llcle lllenggg hthth. PaPaPaP cicicicinggg sssiiiti es were consnsnsnsidididdered

hhe itithihi 55m ffr thth TiTittr tatiio fof iin ttp tt ffo e

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

8

ablation, rapid atrial pacing was performed in attempt to re-induce the arrhythmia. If it remained

non-inducible, the ablation was considered successful. When linear ablation was used across an

isthmus, activation mapping and/or differential pacing on either side of the ablation line was

performed to confirm bidirectional block.

Electrogram measurement protocol

In order to define the lower normal voltage cutoffs in the healthy right and left atria, we analyzed

data from 10 control patients with structurally normal atria and determined the 5th percentile of

the bipolar voltages amplitude. In order to measure bipolar signal duration in normal atria with

both catheters, data was analyzed offline with electronic calipers on the Prucka CardioLab (GE

Healthcare, Waukesha, Wisconsin) recording system using uniform lead gain and paper speed of

200 mm/s. The local atrial signal duration was measured from the earliest initial deflection from

the isoelectric line to the time the last signal component returned to the isoelectric line. In order

to compare differences in electrograms characteristics between the catheters, we analyzed signals

for presence of fractionation (defined as signals with multiple intrinsic deflections), split

potentials (defined as electrograms separated by 30msec by an isoelectric interval), and late

potentials (defined as those displaying an additional signal separated from the local atrial

electrogram by 50msec).

Statistical analysis

Descriptive statistics are reported as mean ± SD for continuous variables and as absolute

frequencies and percentages for categorical variables. Normality of the continuous variables

distributions was assessed using one sample Kolmogorov-Smirnov test and comparisons between

the linear and multielectrode-mapping data were performed using the unpaired Student’s t test or

Mann-Whitney U test as appropriate. Categorical variables were compared using the Fisher’s

ation in normal attriririria a aa w

he Prrucuckkakak CCCCarardidididioLoLLLabababab

e

t o

e differences in electrograms characteristics between the catheters, we analyzed s

ce of fractionation (defined as signals ith m ltiple intrinsic deflections) split

, WaWaWaWaukukukukesessshahahaha, WiWWW sconsin) recording systeeemmm using uniformrr leaeaeaead gain and paper spe

ThThThThe local atriall sigggnnal dududuuratiiiiono waww s memm assurredddd fffrorororom mmm thhheee earrlieestttt iiinitiaalaa dddeefllecttttiooon

tric lililiinenene tttto thhhhe tititime ttthhhhe lassstttt iisisignalll ccccomomompoponent rrreteteteturrrnnnned ddd totototo thththt e isiii oelelelelectcctctric lililine. IIIn o

e diffffffef rences iiin nnn ellllectrogggrams chhhah ra tcteris iitics bbbbettween tthehehee catheheheetet rs, we anaaaalylylylyzezzz d s

fof ff tctiio titi ((ddefifi dd iig lls itithh ltltiiplle ii tnt iri iic dd feflle tctiio )) lplitit

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

9

exact test. A p value <0.05 was considered statistically significant. Analyses were conducted

using SPSS Statistics 20.0 (Chicago, Illinois).

Results

Patient Characteristics and Previous Ablations

Patient characteristics are depicted in table 1. In the derivation group of 10 patients with

structurally normal atria, the mean age was 55±9 years and the mean left atrial diameter was

40±6mm. The mean ejection fraction was 60±10%. All patients had CMR without evidence late

gadolinium enhancement (indicative of scar) in the atria. In the group of patients with scar-

related ATs, 16 had prior percutaneous ablation procedures (median of 2 prior procedures per

patient) and 4 additional patients had history of surgical maze. Six patients had previously

undergone mitral valve replacement surgery. The recurrent arrhythmia was persistent ATs in 14

patients and persistent AF in 6 patients. The mean time from the prior ablation or surgical

procedure to the “current” ablation procedure was 13.3±9.2 months (range, 3 to 23 months).

Mapping density

In the derivation group of 10 patients with structurally normal atria, the number of electrograms

acquired with the multielectrode-mapping catheter was significantly greater than that obtained

with the linear catheter (right atrium 1286±336 [median 1220] vs. 462±216 [median 446],

p<0.01; left atrium 1554±374 [median 1335] vs. 366 ±273 [median 352], p<0.01). The mapping

time was shorter using the multielectrode-mapping catheter (13±7min [median 12] vs. 21±

12mm [median 20], p=0.03). This is likely because each “beat” acquired with the multielectrode-

mapping catheter can record up to 10 overlapping bipolar electrograms compared with only 1

bipolar electrogram recorded with a linear catheter. Similarly, in the group of patients with scar-

related atrial arrhythmias, mapping density was higher with the multielectrode-mapping catheter

off paaaatitititienenenentstststs wwwwitititith h h h scscscscarararar--

s, 16 had prior percutaneous ablation procedures (median of 2 prior procedures p

d

mitral valve replacement surgery. The recurrent arrhythmia was persistent ATs

d

to the “current” p .3±9.2 months (range, 3 to 23 months)

s, 16 hahahad d d prprprior rrr pepp rcutaneous ablation procccedee ures (median oooof ff f 2 prior procedures p

dddd 44 additionaaal lll ppatititienenenentstststs hhhhadadadad hhhhisisisistototot ryrry of fff ssurggiccal mmmazzzzee.e SSSSixxx pppatatatieentstststs hhhhadadadd pppprereeviviviououououslslsly yyy

mimimitrtrtrtralalal vvvalalala vevvv rrrrepepepplalalalacecececememmm ntntntnt sssururururggeryryryy. ThThThThe e e e rererer cucuuurrrrrrrrenenene t t t araara rhrhrhrhytytyty hmhmhmhmiiai wwwwasasas pppperererersisisis sttttenenentt t t ATATATATs sss

d peeeersrssisisisteeentntnt AAAFF FF inininin 666 pppatatatieieientntntntss.s TTTThehehe mmmmeaeaeae n tititimememee ffffrororoommmm thththhee e e prprprprioioior rr abababa lalalalatititionononn ooor rr sususus rgrgrggiciciccal

toto tthee “cuucurrr ene t”t”t”” abbabblallal titttiono prp ococeddede uru e e wawwas s 1313133.33.3±9±9±9±9.22.22 mono thhthhs s ((r(r( ana gege,, 3333 totot 22223333 moontthss)) by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

10

(1858±975 [median 1766] vs. 472±171 [median 452], p<0.01) despite shorter mapping times

(15±6min [median 15] vs. 23± 12min [median 22], p=0.02).

Normal cutoff values

Normal voltage cutoffs for each catheter were established in 10 patients with structurally normal

atria during sinus rhythm. In the right atrium, a total of 4382 electrograms were recorded with

the linear catheter and a total of 11,956 with the multielectrode-mapping catheter. The mean

bipolar electrogram amplitude was similar between the linear and the multielectrode-mapping

catheters (2.6±1.8mV vs. 2.9±2.4mV; p=0.76). The fifth percentile of the normal bipolar voltage

distribution was also similar between the linear and multielectrode-mapping catheters (0.48mV

and 0.52mV, respectively; p=0.68). In the left atrium, a total of 3852 electrograms were recorded

with the linear catheter and a total 16,435 electrograms with the multielectrode-mapping

catheter. The mean bipolar electrogram amplitude recorded was similar between the linear and

the multielectrode-mapping catheters (2.6±1.6mV vs. 2.8±3.2mV; p=0.84). The fifth percentile

of normal bipolar voltage distribution was also similar between the linear and multielectrode-

mapping catheters (0.50mV and 0.52mV, respectively; p=0.80). Using this data, we defined the

catheters.

Electrogram duration during sinus rhythm was shorter with the multielectrode-mapping

catheter. When mapping with the multielectrode-mapping catheter, the mean bipolar electrogram

duration was 32msec +/- 22 (median 30msec; range 18-54ms) and 95% of all electrograms had

duration <46ms. In comparison, when mapping the linear catheter, the mean bipolar electrogram

duration was 44msec +/-24 (median 42msec; range 26-68ms) and 95% of all electrograms had a

duration <58msec.

the normal bippolarararar vvvvo

appingngg cacaththththettteterers s (0(0(0(0.444.488

V c

n

he mean bipolar electrogram amplitude recorded was similar between the linear

e n

bipolar oltage distrib tion as also similar bet een the linear and m ltielectrod

V, rerererespspsps ececcctitititivvelylyly;;;; p=0.68). In the left atriuuuum,m,m a total of 388852 eeeelell ctrograms were rec

neaeaeaearrr r catheter aandd a tootal 11116,433335555 eeeleectrrooograamms wiwwiw thththh thhe mmmultiielleccctrrode-m-m-mappppinggg

he memememeananan bbbbippolllar elelll ttctrogrgramamamam amppplilililitututudededed recordededededdd d wawawawas sisisisimimimim lall r bebbb twtwwweeeeeee n ththhhe lililil near

ectrodedd -mappppipipiinggg cathhheters (2(2(2.6666 1±1±1 66.6mV vs. 2222 8.8±3±3±3± 22.2mVmVVV;;; ; p=pp 000.84848484).).).) TTTThhehh ffffifififi thththth pppeeere cen

bibi lla ltlt didi tst iribb titi lls isi imilla bbett thth lili dnd lltiti lel ttr dod

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

11

Low voltage (“scar”) mapping

We compared mapping resolution between the two catheters in low voltage and scar tissue

during sinus rhythm. In patients with scar-related atrial arrhythmias, the total area of low bipolar

voltage (defined as <0.5mV) measured using the multielectrode-mapping catheter was

significantly smaller than that measured using the linear catheter (14.7cm2 [median 15.2; range

7-48cm2] vs. 20.4cm2 [median 22.4; range 9-55cm2]; p=0.02). In addition to smaller low voltage

“scar” area, the bipolar voltage distribution within this area of low voltage was higher using

multielectrode-mapping catheters with a mean bipolar voltage of 0.28+/- 1.2mV compared with

0.17+/- 1.0mV measured with the linear catheter (p=0.01). This resulted in improved delineation

of the low voltage zones (Table 2 and Figures 1 and 2).

Late potentials within the area of low voltage (<0.5mV) were more frequently recorded

with the multielectrode-mapping catheter (28.2+/-14.5% vs. 13.6+/-7.8% of total low voltage

signals; p=0.01). Electrogram fractionation within the area of low voltage was also more

frequently recorded with multielectrode-mapping catheters (68.8+/-22.6% vs. 38.6+/-12.4% of

total low voltage signals; p<0.01). These signals were essentially seen only in the group of

patients with scarred atria. The frequency of split potentials was similar between the catheters.

Determinants of mapping resolution within scar

We examined the individual contribution of 1) mapping density; 2) electrode size; and 3)

interelectrode spacing on catheter mapping resolution within the zone of low voltage.

In order to examine the relationship between mapping density and mapping resolution,

each pair of maps was reanalyzed and density adjusted by excluding data points from the map of

greater original density in order to achieve similar data density with homogenous point

distribution. In order to minimize bias, all data points were exported to a Matlab platform and

+/- 1.2mV comppararrrededede

ed inn iiiimpmprorovevedd dd dedededelilililinne

v

r

u a

recorded ith m ltielectrode mapping catheters (68 8+/ 22 6% s 38 6+/ 12 4%

vollltatatatagegegeg zzzzononono esss ((((TaTT ble 2 and Figures 1 annnd ddd 2)222 .

eeee ppopop tentials wwitthinnn ttthhhe aaarrrea ofofoff lowoow vooltttagee (<0000.5.5.5mVmmVm ) weww re mmorrre freqqqqueueueu nntlyly recececor

ultielelelelecttctrrororode-mapappipiing caththththetteteter (28282828 222.2r +/+/+/+/ 11-14.44 5%5%5%5% vvvvs. 11133.33 6666+/+/+/+/ 7-777 88.8%%% % ofofoff tttotoototal llllow v lllolttta

0.0111).).). ElElElectrogogoggram frff actiiionatioi n iwii hththin thhhe area offf loww vollltatatagegegeg was alllso momommorrrer

ddedd iithth lltiti lel ttr dod iin thth tet ((6868 88+/+/ 2222 6%6% 3388 6+6+// 1212 44%%

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

12

distances between points were calculated based on the x, y and z coordinates. Exclusion of points

was performed blindly based on data point coordinates and aimed to create a similar point data

density between maps. The resultant mean mapping density was 12±3mm between points with a

bipolar voltage <0.5mV measured with the multielectrode-mapping catheter remained

significantly smaller than that measured with linear catheter (15.4cm2 [median 12.8; range 7-

32.6cm2] vs. 22.4cm2 [median 21.8; range11-44cm2]; p=0.03). The mean bipolar voltage

amplitude within this area of low voltage remained higher when using the multielectrode-

mapping catheter (0.26+/-0.12mV vs. 0.17+/-0.09mV; p=0.01). This data suggests that mapping

density is not a significant determinant in the differential resolution between the catheters.

In order to examine the relationship between electrode size and bipolar voltage

amplitude, we first attempted to control for the other two variables, mapping density and

interelectrode spacing. Mapping density was controlled as described above with all paired maps

having similar mapping density. As the catheters do not have similar interelectrode spacing, we

reanalyzed maps made with the multielectrode-mapping catheter to only include data from

bipolar electrode pairs separated by 6mm rather than 2mm. In this configuration, the relationship

of interelectrode spacing between the catheters had reversed with the multielectrode-mapping

catheter having a larger center-to-center interelectrode spacing compared with the linear catheter

(7 vs. 4.75mm). The total area of bipolar voltage <0.5mV measured with the multielectrode-

mapping catheter remained smaller than that measured with the linear catheter (18.6cm2 [median

15.2; range 9-24.8cm2] vs. 22.4cm2 [median 23.1; range 11-36.6cm2]; p=0.04). The mean bipolar

voltage amplitude recorded with the multielectrode-mapping catheter remained higher (0.22+/-

0.10mV vs. 0.17+/-0.09mV; p=0.04). This data suggests that smaller size electrodes are at least

the multielectrodededee---

data susuggggesesttstts ttthahahh t t mammmap

n

o

ode spacing. Mapping density was controlled as described above with all paired m

milar mapping densit As the catheters do not ha e similar interelectrode spacing

nottt aaaa ssssigigigninininifififificaantntntnt determinant in the differrrenene tial resolutiooon bebebettwt een the catheters.

orrrrdeeeer to examiine thehehe relatatationsshhhih ppp bbetwweeenn eeleccctrtrtrrodododdee siiizeee annd bipipippoolo ar vvvvoooltttagge

we fifififirsrrsttt attemptttted ddd ttto contrtrtrtrollolol for ttthehehehe oooththther tttwowo vvvvarriaiaaiablblblblesesess, mapping g gg dedededensititity anddd

ode spapp iciinggg. MMMaM ppppppinii g gg dedd nsiiti y yy was controllllll deddd as deddd sc iiribebeeed dd abababooovo e iiwii hthh alllll ppppaiaiaia rrrer d m

milil ipi dd isitt AAs tthhe tathhette dd tt hha iimiilla iintte lle tct dde ici

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

13

partially responsible for the differential resolution between the catheters.

Lastly, we examined the relationship between interelectrode spacing and bipolar voltage

amplitude. A subset of 10 patients with scar-related atrial arrhythmias underwent mapping with

the multielectrode-mapping catheter recording both bipolar electrode pairs separated by 2 and

6mm. This data was then separated into two datasets, one containing only data recorded using

bipolar electrodes separated by 2mm and a second containing only data recorded using bipolar

electrode separated by 6mm. The total low voltage area and mean bipolar voltage amplitude was

calculated for each separate map. The total area of bipolar voltage <0.5mV measured with

interelectrode spacing of 2mm was smaller than that measured with interelectrode spacing of

6mm catheter (15.4cm2 [median 14.0; range 8-23.5cm2] vs. 19.2cm2 [median 18.6; range 10-

28.9cm2]; p=0.03). The mean bipolar voltage amplitude within this area of low voltage was

higher when mapping with interelectrode spacing of 2mm (0.26+/-0.11mV vs. 0.22+/-0.16mV;

p=0.03). This data suggest that interelectrode spacing is a determinant of mapping resolution

within scar tissue.

Arrhythmia Mapping

Twenty patients with scar-related atrial arrhythmias had 26 ATs, however only 23 had TCL

200ms (mean 274±56ms) that allowed mapping. Five ATs were not mapped because they

stopped spontaneously before mapping and did not recur. Activation mapping was performed

with the multielectrode-mapping catheter in all 18 sustained ATs and with the linear catheter in

13 of the 18 (72.2%). In effort to limit bias, the sequence of mapping alternated between the

catheters, with the linear catheter used first in 8 patients and the multielectrode-mapping catheter

used first in 5 patients. The mechanism of the tachycardia was defined as macroreentry or focal

microreentry on the basis of the activation map. In macroreentrant atrial tachycardias, the circuits

5mV measured wwitititith h hh

terelelel tctctrorodededd sspapapp cicicicingngngng o

e 2 2 2 0

p s

e 6

h o

r tiss e

eterrrr (((1515151 4.44cmcmcmc 2 [m[m[m[median 14.0; range 8-23.555cmcmc 2] vs. 19.2cmmm2 [m[m[m[median 18.6; range 10

pp=0=0=0=0.03). The memem annn bbbipooolalalaar voollltl agaagee ammmpplittude wiwiwiw thththhinn ttthihihis arreaa ooof ff low vovoolttaage waww s

en maaaappppppininining g wiiiththth iii ttnterelectrtrtrtroddodode sppacacaca iniining offf 2222mmmmmmm ((((00.00 2626262 +/+/+/ 0-00.11111m1 V VV vvvsss.s 0.2222222+/+/+/+ -000 11.116

his ddad ta suggggegegesssts tthahh t iini terellell ctrodedd spapp ciiinggg iiis a ddded termininnnant ofofofo mappppppinii g gg rerereresososos lllul tio

titi

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

14

traversed large portions of the atrium while in focal atrial tachycardias a point source with

centrifugal activation from this center was identified. The mechanism was macroreentry in 16 of

18 (88.9%) and focal in 2 of 18 (11.1%). The most common atrial tachycardia was a

macroreentrant circuit involving the mitral isthmus (8 of 16; 50%) followed by macroreentrant

circuit involving the left atrial roof (4 of 16; 25%). The third most common tachycardia (3 of 18;

17%) involved the septum, and there was 1 right-sided atrial tachycardia.

Activation mapping with the multielectrode-mapping catheter included a mean of

1172±346 points (median 1220) with an average mapping time of 13±8 minutes (median 14).

The activation map constituted an average of 92±8% of the TCL. All circuits involved the area

of low voltage as defined with the multielectrode-mapping catheter during sinus rhythm. In 12 of

the 16 macroreentrant ATs mapped with the multielectrode-mapping catheter, activation

mapping was also performed using the linear catheter. The mean number of activation points per

map was smaller (241±73; median 228; p=0.02) despite similar mapping time of 15±11 minutes

(median 15; p=0.72). In comparison to mapping with the multielectrode-mapping catheter,

activation maps constituted an average of 68±32% of the TCL (p=0.01). In 4 ATs that occurred

in patients with limited atrial scar, mapping with either the linear or the multielectrode-mapping

catheter resulted in nearly complete activation map constituting >90% of the TCL. However, in 8

ATs that occurred in patients with extensive atrial scarring, mapping with the linear catheter was

associated with limited activation mapping constituting only 53±11% of the TCL compared with

90±8% when the same AT was mapped with the multielectrode-mapping catheter (Figure 3 and

4). In these cases, mapping with the linear catheter demonstrated significantly lower mean

voltage amplitude that was coupled with highly fractionated and non-distinctive electrograms,

limiting accurate activation time annotation (Figure 5). Overall, 54.4% of all low voltage data

8 minutes ((medianannn 114

circuiuiiitststt iiiinvnvololllveved d ththththeeee a

t n

c

was also performed using the linear catheter. The mean number of activation poin

m n

5; p 0 72) In comparison to mapping ith the m ltielectrode mapping catheter

tagegegege aaaass dededeefifififinned dd wiww th the multielectrode-mmmapapping catheteeer dududurrring sinus rhythm. In

rrror rrrer entrant ATTss mammapppeddedd witttthhh h thhhe muultttielecctrooodedede-m-m-mmapppping caathhhhettter, acacactitt vavationnn

was allllsososso pppperformedddd u iising ttthehehehe lllineaarrrr cacacaththththettter. ThThThTheeee memememean nnnnumbbber offff aaaactcctctiivatttiiion poiinii

malllllel r (2(2(2414141±7±7±77333;3 medddiiai n 222222288;8 ppp 00=0.0002222) ) ) despppiiti e siiii iimiillal r mamappppppinininng g g g ititime offf 15151515±1±1±1±11111 min

55 00 7272)) II iis tt iin iithth tthhe ltltiielle tct dde ipi thth tet

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

15

points recorded with multielectrode-mapping catheters had distinct electrograms that allowed

annotation of local activation time compared with only 21.4% of all low voltage points recorded

with linear catheters (p=0.02). Ablation was successful in 15 of the 16 macroreentrant circuits

and in the 2 focal arrhythmias. In 1 patient with macroreentrant circuit involving the interatrial

septum ablation was unsuccessful.

Atrial Pacing Threshold

We compared the pacing threshold during tachycardia between the linear and multielectrode-

mapping catheters at similar atrial sites. In 13 patients in whom the arrhythmia was mapped with

both catheters, overdrive pacing of the tachycardia was performed with both the linear and the

multielectrode-mapping catheters (n=54 and 47, respectively). Pacing with capture was more

frequent with multielectrode catheters (66.7% vs 33.4%; p=0.01). Moreover, the pacing

threshold was lower using multielectrode-mapping catheters as 57.7% of pacing sites had

threshold compared with only 25.5% when pacing from a linear catheter (p=0.02).

Discussion

Major findings

This study established the normal bipolar voltage distributions in the atria for both a linear

catheter with 3.5mm distal electrode and 1mm multielectrode-mapping catheter. In addition, this

study compared the mapping resolution in low voltage and scar with both catheters.

The major findings are: 1) bipolar voltage amplitude in healthy atria is similar between

3.5mm and 1mm electrode catheters with a 5th percentile of 0.48mV and 0.52mV, respectively;

2) mapping resolution within areas of low voltage and scar is enhanced with 1mm electrode

catheters; 3) electrode size and interelectrode spacing were major determinants of mapping

resolution within areas of low voltage and scar; 4) lastly, arrhythmia mapping using activation

rrhyty hmia was mapappppepepp

h botottth hhh thththhee lilililineneaar aaaandndndnd

o

i

w

=

odedede-m-m-mapapappipipipinng cacacacatheters (n=54 and 47, reeespspspeectively). Pacacacing ggg wwwith capture was mo

itttth multielectrrode caathetetteteeers (6(6(6(66.777%% vvs 33.44%;;;; pppp=0=0=00.01). Mooreeovvveer, thhhhe papaccinggg

was lololooweewewerr usiniii g multltltieii lectctcttrorororodddde-mmapapapappiipipingng caththththetetteterererers aasasas 5555777.7 7%7%7%% of fff paacicicicinngngn sitititi es hhhh dddad

cccoc mpppareddd wiititi h onlylyly 2222555.5 5%%%% whehhh n papp cinggg ffffrom mm aaa a lilililinear caththththeteteteterererer (((p=pprr

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

16

and/or overdrive pacing techniques was more accurate using 1mm electrode catheters.

Three-dimensional (3D) electroanatomic mapping systems have been developed to assist

with mapping and ablation of cardiac arrhythmias. These systems have become an essential tool

for mapping complex arrhythmias and are frequently used to assess the underlying substrate for

presence of low voltage areas, so called “scar”. Accurate detection and characterization of atrial

scar with electroanatomic mapping is essential for catheter ablation of atrial arrhythmias. Normal

electrographic criteria in the ventricle were defined by Cassidy and Marchlinski,9, 10 however

limited data exist regarding the normal voltage distribution in the atria. Kapa et al have defined

the normal bipolar voltage distribution in the left atrium using 3.5mm Thermocool® catheter. In

10 patients with paroxysmal AF, the mean bipolar voltage amplitude was 1.44±1.27mV, and

95% of all points demonstrated a bipolar voltage amplitude >0.45mV. Our study confirms this

observation and extend its finding also to the right atrium. We found that 95% of all

electrograms in the right and left atria had a bipolar voltage amplitude >0.48mV. In addition, we

measured the distribution of electrograms duration in healthy atria and found that 95% of all

electrograms had a duration < 58ms.

Iatrogenic AT are unfortunately common after AF ablation, particularly in patients with

persistent AF where additional ablation sets often include linear lesions and ablation at sites of

complex fractionated electrograms. The mechanism of these ATs is typically macroreentry but

also sometimes microreentry involving preexisting or iatrogenic ablation-related scar tissue.

These arrhythmias can be challenging to map using standard linear catheters because of significant

scar coupled with fractionated and multicomponent electrograms, limiting activation and

entrainment mapping. Patel and colleagues have reported the feasibility to rapidly map and

successfully ablate these arrhythmias using the Pentaray® multielectrode-mapping catheter in post-

a. Kappa et al havee ddddefefee

Thermrmococoooollll® ® ®® cacaththththetetetete

with paroxysmal AF, the mean bipolar voltage amplitude was 1.44±1.27mV, an

points demonstrated a b olar voltage amplitude >0.45mV. Our study confirms t

n

ms in the right and left atria had a bipolar voltage amplitude >0.48mV. In additio

he distrib tion of electrograms d ration in health atria and fo nd that 95% of a

wiwiwiththhth pppararrroxoxoxo ysssmmamm l AF, the mean bipolar vvvololtage amplituuude wwwwas 1.44±1.27mV, an

ppppoiiiints demonsttratededed a bbbipipipipolarar volooltagge ampmplituuudedede >>>>00.44545mVV. OuOuuur studdddy coonnfirmsmm t

n anddd d exexextetetete dnd iiittts ffffinii diididing alslslssooo to thehehehe rrigiigighhhth atttriiiui m.mmm WWWWeeee ffounununund ddd thththat 995%5%5%5% of allllll

ms iiiin hhthe righghght tt anddd d llleffft atriaiii hadddd a bbbipipipolar v lollltat gegg ampppliitutututudedd >>>>0.00 4848484 mVVV. InInInIn aaaadddddddditio

hhe ddiisttribib ttiio fof lle tct dd titi ii hhe lalthth tat iri dd ffo dd thth tat 995%5% ff a

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

17

PVI patients with ATs. 11

In this study, we established the normal atrial electrogram characteristics of 2 commonly

used catheters: a standard mapping/ablation catheter (Thermocool®) and a multielectrode-mapping

catheter (Pentaray®). While the resolution of mapping between the catheters was similar in healthy

atrial tissue, they significantly diverge in low voltage and scar tissue. The resolution of electrical

mapping is influenced by multiple parameters including electrode size, interelectrode spacing, angle

of incidence (catheter orientation relative to the surface), the vector of wave propagation, and

filtering. Their combined effect is associated with significant variations in the recorded bipolar

voltage amplitude at any single recording point. While these changes may not be as clinically

important in the normal healthy tissue whereas a bipolar voltage amplitude variation between 0.5-

4.0mV represents normal tissue, such variations in areas of low voltage and scar are significant and

determine feasibility to identify surviving myocardial channels and “isthmuses” often present in

zones of low voltage. In this study we found that smaller electrodes with closer interelectrode

spacing provide higher resolution in scar mapping. Maps made with multielectrode-mapping

catheters usually contained more data points, and points acquired with increased variability in the

angle of incidence and the relationship to the vector of propagation. They may thus be less

subjective to the individual confounding effects of bipolar voltage amplitude measurement. We

found that mapping density alone is not responsible for the differences in mapping resolution within

scar and that smaller electrodes and closer interelectrode spacing are significant determinants of

mapping resolution. Smaller electrodes have smaller electrical fields of view and smaller antenna,

and as such are subjected to less averaging and cancellation effects. A bipolar electrode pair with

closer interelectrode spacing record data from smaller tissue diameters and is therefore more

sensitive to detect surviving myocardial fibers in zones of generally low voltage “channels”. It also

in the recorded bipipppololololaa

ay notott bbbbee asas cclilililininicaaaallllllllyy

n the normal healthy tissue whereas a bipolar voltage amplitude variation between

r n

feasibility to identify surviving myocardial channels and “isthmuses” often present

w

o ide higher resol tion in scar mapping Maps made ith m ltielectrode mapping

n tthehehe nnnnororormamamm l hehehealaa thy tissue whereas a bippppololololaar voltage ampmm lituuuuddde variation between

reeese eeene ts normall tiissueuue, suuuchchchh varriiiai tiiioons ininn areeaas oooff ff lololow ww w voooltttage anand ddd sscar aaraa ee e ssiggniffficccanaa

feasibibibbillililititityyy to iiiideddd tttntififfify survivivivivinining myyocococo arararddidid alll chhhah nnnnnnnn lels ss aaaand ddd “i“i“i“ sttthmhh usessss””” ofo ten presentt t

w v lolltagegg . InII ttthihhih s st duddy yy we fffounddd thahh tt sm llallell r lelecttr doddess wwwwitii h hh clccc oser iiiinterelelelelecececectrtrrtroode

idid hihi hgh lol ttiio iin iin MM dde itithh ltltiielle tct dde iin

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

18

has a more distinct electrogram with shorter electrogram duration that allows more accurate

annotation of activation time. Lastly, the pacing output threshold within the zone of low voltage and

scar is lower with small electrode catheters, likely due to the increased electrical “current” density at

the electrode-tissue interface.

In addition, pacing from a multielectrode-mapping catheter placed in or around a

macroreentrant circuit can be used to determine the mechanism of the tachycardia. If pacing

performed during AT from a site that demonstrates later activation relative to its neighbors results in

orthodromic capture of these earlier “upstream” neighboring sites, the mechanism must be reentry.

Barbhaiya and colleagues have recently reported the utility of such approach to define the

mechanism of atrial tachycardias. 12

Study limitations

This study includes a relatively small cohort of patients. While mapping data with the linear catheter

was confirmed by contact force measurement, such data was not available for maps made with the

multielectrode-mapping catheter. However, although differences in tissue contact can affect bipolar

voltage amplitude, it is unlikely to account for the differences between the catheters. First, all maps

performed with multielectrode-mapping catheters had similar volumes compared to maps made

with linear catheters. Second, points were only accepted if they were within 5mm from the original

shell made with the linear catheter. Lastly, in the derivation cohort of patients with normal atria, the

bipolar voltage amplitude was similar between the catheters. In patients with ATs, only 13 of the 18

ATs mapped with the multielectrode-mapping catheter were also mapped with the linear

catheter. Although the number of ATs mapped with both catheters was small, the data was

highly consistent. Electrogram duration was measured using fixed electrogram gain; however

data acquisition was obtained using a standard amplifier with variable gain. The clinical impact

mechanism must be e rerereree

oachh tttto o dddedefifififinene tttthhhehe

m 12

t

i

med by contact force measurement, such data was not available for maps made with

ode mapping catheter Ho e er altho gh differences in tiss e contact can affect b

m offf atatatatririririalalall tatatatachcc ycycycycardias. 12

taaaatiiiions

incluludedededesss a relalll tititivelylyll smallllllll ccccohhohohort ofofofof ppatattatiiiei ttnts. WWWWhihihihillele mmmmappppipipip ngng ddddata wiwiwiwithththth thhhe lililinear c

med ddd bybyby contactctctt fforce measurement, such dddata was not avvaiaiaia lablblble eee fofff r mapspp mmmmadadadade eee with

dde iin thth tet HHo altlthho hh didiffff iin ttiis tnt tt fafffe tct bb

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

19

of mapping with small electrode catheters on long-term clinical outcome is outside the scope of

this study and remains unanswered. Finally, it may be economically challenging to use the

Pentaray catheter in addition to a circular mapping catheter commonly used during routine AF

ablation procedures. However, in our experience, we have been able to perform the entire

ablation procedure using just the Pentaray® catheter instead of the circular catheter, including

creating the left atrial geometry and verifying entrance and exit blocks.

Conclusions

This study established the normal bipolar voltage criteria in the atria for both a standard linear

mapping/ablation catheter with 3.5mm distal electrode (Thermocool®) and a multielectrode-

mapping catheter with 1mm electrodes (Pentaray®). In addition, this study showed that catheters

with smaller electrodes and closer interelectrode spacing have significant advantage in mapping

atrial scar. This technique can facilitate successful ablation of scar-related atrial tachycardias.

Conflict of Interest Disclosures: Elad Anter receives research grants and speaking honoraria

from Biosense Webster and Boston Scientific. Mark E. Josephson receives research grants and

speaking honoraria from Medtronic. Cory M. Tschabrunn has no relevant disclosures.

References:

1. Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA, Crijns HJ, Damiano RJ, Jr., Davies DW, DiMarco J, Edgerton J, Ellenbogen K, Ezekowitz MD, Haines DE, Haissaguerre M, Hindricks G, Iesaka Y, Jackman W, Jalife J, Jais P, Kalman J, Keane D, Kim YH, Kirchhof P, Klein G, Kottkamp H, Kumagai K, Lindsay BD, Mansour M, Marchlinski FE, McCarthy PM, Mont JL, Morady F, Nademanee K, Nakagawa H, Natale A, Nattel S, Packer DL, Pappone C, Prystowsky E, Raviele A, Reddy V, Ruskin JN, Shemin RJ, Tsao HM, Wilber D, Heart Rhythm Society Task Force on C and Surgical Ablation of Atrial F. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. Developed in partnership with the

or bobooothththth aaaa sssstatatatandndndndarararard d dd lilililinnnn

blation catheter with 3.5mm distal electrode (Thermocool ) and a multielectrode

a t

er electrodes and closer interelectrode spacing have significant advantage in map

a

blationonon cccataa hehh teeeer rrr with 3.5mm distal electrododode (Thermocool )))) and a multielectrode

atttht eeete er with 1m1m1m1 m m m eleelecececectrtrtrtrododododesss (((PePePePenttarayayy®). IIn adadadaddidididitititit on,, thtththisisis sttudddy y yy hshshhowowowwedededed ttthahahahat ttt ccacc t

er eeeelelelectctcttrororoodedededes ananand d dd ccclc ososososer iiiintntntn erererrelelelelecccctrtrtrt odododdee spspspspacaca ininining g g g hahahavevevev sssigigiggnininin fififif cacacantnnn aaadvdvdvdvananananttat gegegeg iiiin n nn mamamamap

Thiiiisss tetetechchchnininiquququeeee cacacac nnn fafafacicicilililitataatatetete ssssucuucuccececessssssssffuf l ll ababablalalaatitititionononn ooooff f scscsccarararr--rereelalalateteteted dd d atatatriririialalala ttacacaca hyhyhyhycacacaardia

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

20

European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology (ESC) and the European Cardiac Arrhythmia Society (ECAS); and in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the Society of Thoracic Surgeons (STS). Endorsed by the governing bodies of the American College of Cardiology Foundation, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, the Asia Pacific Heart Rhythm Society, and the Heart Rhythm Society. Heart Rhythm. 2012;9:632-696 e21.

2. Bhargava M, Di Biase L, Mohanty P, Prasad S, Martin DO, Williams-Andrews M, Wazni OM, Burkhardt JD, Cummings JE, Khaykin Y, Verma A, Hao S, Beheiry S, Hongo R, Rossillo A, Raviele A, Bonso A, Themistoclakis S, Stewart K, Saliba WI, Schweikert RA and Natale A. Impact of type of atrial fibrillation and repeat catheter ablation on long-term freedom from atrial fibrillation: results from a multicenter study. Heart Rhythm. 2009;6:1403-1412.

3. Tzou WS, Marchlinski FE, Zado ES, Lin D, Dixit S, Callans DJ, Cooper JM, Bala R, Garcia F, Hutchinson MD, Riley MP, Verdino R, Gerstenfeld EP. Long-term outcome after successful catheter ablation of atrial fibrillation. Circ Arrhythm Electrophysiol. 2010;3:237-242.

4. Deisenhofer I, Estner H, Zrenner B, Schreieck J, Weyerbrock S, Hessling G, Scharf K, Karch MR, Schmitt C. Left atrial tachycardia after circumferential pulmonary vein ablation for atrial fibrillation: incidence, electrophysiological characteristics, and results of radiofrequency ablation. Europace. 2006;8:573-582.

5. Gerstenfeld EP, Marchlinski FE. Mapping and ablation of left atrial tachycardias occurring after atrial fibrillation ablation. Heart Rhythm. 2007;4:S65-72.

6. Jais P, Sanders P, Hsu LF, Hocini M, Sacher F, Takahashi Y, Rotter M, Rostock T, Bordachar P, Reuter S, Laborderie J, Clementy J, Haissaguerre M. Flutter localized to the anterior left atrium after catheter ablation of atrial fibrillation. J Cardiovasc Electrophysiol. 2006;17:279-285.

7. Gerstenfeld EP, Callans DJ, Sauer W, Jacobson J, Marchlinski FE. Reentrant and nonreentrant focal left atrial tachycardias occur after pulmonary vein isolation. Heart Rhythm. 2005;2:1195-1202.

8. Chugh A, Oral H, Lemola K, Hall B, Cheung P, Good E, Tamirisa K, Han J, Bogun F, Pelosi F, Morady F. Prevalence, mechanisms, and clinical significance of macroreentrant atrial tachycardia during and following left atrial ablation for atrial fibrillation. Heart Rhythm.2005;2:464-472.

9. Cassidy DM, Vassallo JA, Marchlinski FE, Buxton AE, Untereker WJ, Josephson ME. Endocardial mapping in humans in sinus rhythm with normal left ventricles: activation patterns and characteristics of electrograms. Circulation. 1984;70:37-42.

oooooooopepepeper r r r JMJMJMJM,,, BaBaBaBalalalala RRRR, GaGaGaGaoutcocomeme aaftftftfterer ssucucccccceces010;3:3:3:3:232323237777 242424242222

ofer I, Estner H, Zrenner B, Schreieck J, Weyerbrock S, Hessling G, Scharf K, Kr

Eu

feld EP, Marchlinski FE. Mapping and ablation of left atrial tachycardias occurri

ofofofferrerr I, Estnnnnererer HHHH, ZrZrZrenenennenenen r B,B,B,B SSSSchhchrerereieeeckckck J, WeW yeyeyerbrbrbrbrororor ckkkk SSSS, , HeHeHeessss lingngngng GGGG, Sccchahahaarfrfrf KKKK, Kittttt CCC.C Left atriall taccchhhycaaardrdrdr ia aaffftf eeer circucuumfferrennntititit alalal puulmomomonaryry veieieie n abblalalal titt oonn foorrr aaatr: ininincicicidence,e,e,e, elecctrooopphysssioioiololl gigigicaccc lll cchc arararaaacteeriristicicicicsss, aaaannd rrressssultss oof rarararadid offffrererequueencyyy uropapaacecece. 222000006;66 88:88 575757333-3 582.222

feldddd EEEPP,P MMMarchchchhliiinskikiki FFFE.EE MMMMappppipipinggg and ablblblatiiioi n ffoff lllefffftt atatatat irii lall ttttaaaca hyhyhyh cardddiaii s ococococcuccc rrifibrillationononon aaaablblbblatatatatioioioion.nn.n HeHeHeHeararara t t t RhRhRhRhytytytythmhmhmhm. 202020200707007;4;4;4;4:S:S::S65656565-7-7-772.2.2. by guest on June 23, 2018

http://circep.ahajournals.org/D

ownloaded from

DOI: 10.1161/CIRCEP.114.002737

21

10. Marchlinski FE, Callans DJ, Gottlieb CD, Zado E. Linear ablation lesions for control of unmappable ventricular tachycardia in patients with ischemic and nonischemic cardiomyopathy. Circulation. 2000;101:1288-1296.

11. Patel AM, d'Avila A, Neuzil P, Kim SJ, Mela T, Singh JP, Ruskin JN, Reddy VY. Atrial tachycardia after ablation of persistent atrial fibrillation: identification of the critical isthmus with a combination of multielectrode activation mapping and targeted entrainment mapping. Circ Arrhythm Electrophysiol. 2008;1:14-22.

12. Barbhaiya CR, Kumar S, Ng J, Tedrow U, Koplan B, John R, Epstein LM, Stevenson WG , Michaud GF. Overdrive pacing from downstream sites on multielectrode catheters to rapidly detect fusion and to diagnose macroreentrant atrial arrhythmias. Circulation. 2014;129:2503-2510.

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

22

Table 1: Baseline Patient Characteristics

Variable Validation group(n=10)

Scar-related atrial arrhythmias(n=20)

Age, y 55.2±9.3 64.2±11.3

Gender, male 7 (70) 14 (70)

LA diameter, mm 40.4±6.1 56.7±11.5

LVEF, % 60.3±9.7 48.4±8.4

No. failed AADs 1 (0-2) 2 (1-3)

Mitral Regurgitation 27 (67.5) 45 (70.3)

0 (0) 11 (55)

Failed previous ablations 0 (0) 2 (0-4)

Surgical MAZE 0 (0) 4 (20)

Surgical MV replacement 0 (0) 6 (30)

Presenting arrhythmia

Paroxysmal AF 10 (100) 0 (0)

Persistent AF 0 (0) 6 (30)

AT 0 (0) 14 (70)

Values are expressed as mean ± SD, median (range) or n (%).AADs=antiarrhythmic drugs; AF=atrial fibrillation; AT=atrial tachycardia LA=left atrium; LVEF=left ventricular ejection fraction; MV=mitral valve

2 2 22 (1(1(11-3-3-3-3))))

45454545 ((((70707070 3333))))

v

M

M

0 00 (0(0(0) 1111111 (555555))))

viououousss ablatiiitionooo ss 0 (0(0(0)) ) 2 (0(0(0( -44)

MAZZZEEEE 0 0 0 (0(0(0( ) 4 444 (2(2(220)0)0)0)

MV replacccememememenenenentttt 0 000 (0(0(0(0) ))) 6 666 (3(3(3(30)000 by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

23

Table 2: Comparison of low voltage and scar surface area

Linear catheter Multielectrode-mapping catheter P (linear vs. multielectrode-mapping catheter)

Total low voltage area <0.5mV (cm2) (median, 25%, 75%)

20.4cm2 [9-55cm2] 22,4, 18.1, 50.6

14.7cm2 [7-48cm2] 15.2, 9.2, 43.6 0.02

Intermediate area 0.25 - 0.5mV (cm2) (median, 25%, 75%)

6.1±5.9 5.2, 3.8, 9.9

10.2 ±4.3 8.8, 4.7, 11.6 0.02

Dense scar <0.25mV (cm2) (median, 25%, 75%)

14.2±8.1 16.6, 10.2, 18.5

4.3±3.6 4.0, 2.1, 6.8 0.01

Values are expressed as mean ± SD, range [ ]

9.2, 43.6

6 1±5 9 10 2 ±4 36.1±5.9 5.2,2,2,2, 333.88,,,, 9.9.9.9.9 9 9

10000.2.22.2 ±4.3 88.8.8 8,8,8,, 4444.7, 11111111.6...

1414144.2.2.2.2±8±8±8±8.1... 16161616.6.66,, 101010.2.222,, 188188.5.55

4.4.4.4.3±3±3±3±3.3.3.3.6 66 6 4.4.4 0,00, 2222.1.11,, 6.66.6 888

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

24

Figure Legends:

Figure 1: Left atrial bipolar voltage maps (0.10-0.50mV) in the posterior-anterior view recorded

with a standard linear catheter (panel A) and a multielectrode catheter (Panel B) in a patient

with structurally normal left atria. The left atrial bipolar voltage amplitude was similar between

the maps with 95% of all electrograms >0.5mV. In contrast, in a patient with scar-related atrial

tachycardia, the bipolar voltage amplitude measured with the linear catheter (Panel C) was

significantly lower than the one measured with the multielectrode catheter (Panel D).

Figure 2: Left atrial bipolar voltage maps (0.10-0.50mV) in the anterior-posterior view recorded

with a multielectrode catheter (Panel A) and a linear catheter (Panel B) in a patient with scar-

related atrial tachycardia. Mapping with the multielectrode catheter demonstrated a significantly

smaller area of low voltage and “scar” in the anterior peri-mitral area. The two catheters were

then placed in contact with the zone of presumed “scar” as recorded with the linear catheter but

not with the multielectrode catheter (Panel C). The mean bipolar voltage amplitude recorded

with the multielectrode catheter at this location was 1.15 ± 0.7mV with mean electrogram

duration of 42 ± 11msec and minimal fractionation (Panel D), suggestive of non-scar tissue.

Figure 3: In a patient with history of surgical maze, mitral valve replacement and persistent

atrial tachycardia, left atrial bipolar voltage maps were performed using both a multielectrode

catheter (Panel A) and a standard linear catheter (panel B). Mapping with the multielectrode

catheter demonstrated smaller “scar” size with an overall higher bipolar voltage amplitude.

When the bipolar voltage maps were displayed at a range of 0.1 to 025mV, the map made with

heter (P( anel D)).

L c

t c

a c

e e

d in contact ith the one of pres med “scar” as recorded ith the linear catheter

Leftftft aaaatrrtriaiaiaal lll bibbb poooolllal r voltage maps (0.10-0.5550m00mV) in the anananteriririiooroo -posterior view rec

tiiiiellllectrode cattheterrr (((Pannneelee AAAA)))) anndd a llinnnearr ccattttheheheh teteteter (PPPannel BB) inninn a patatattieieennt wwittthh sc

al tacccchyhyhycccacardiaiii . MMMaM ppinii g wiwiwwithththth the mmmmullulultitititielllecttttrododdodeeee caaaththththetetetererere ddddemonststststrararaattted a iisiigniffifificii

ea of fff lol w voltll agagagage and dd “s““ car”””” in hhthe anteriiior ppperiii- iimitrallll aaaarrrer a. TTTThhheh two cattheheheetetetetersrrr we

dd iin tta tct itithh thth ff ded ““ ”” ddedd iithth tthhe lliin thth tet

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

25

the multielectrode catheter demonstrated improved delineation of the low voltage zone, revealing

an area of relatively preserved myocardium (“channel”) that was not demonstrated in a map

made with the linear catheter (Panels C and D). When the clinical atrial flutter was mapped, this

“channel” proved to be the isthmus of the tachycardia as seen by the activation map (Panel E).

When the multielectrode catheter was placed over the isthmus, >75% of the tachycardia cycle

length was recorded at this single point acquisition (Panel F). The tachycardia terminated with

ablation at this site.

Figure 4: In a patient with macroreentrant left atrial flutter, the multielectrode catheter and the

linear catheter were placed at a similar position at the area of “early meet late”. The linear

catheter was positioned in a perpendicular orientation to the tissue with its distal electrode

applying 9gr of tissue contact force. The multielectrode catheter was positioned parallel to the

tissue (panel A). While the linear catheter recorded low, far-field, signal with amplitude of

0.12mV, the multielectrode catheter recorded sharp, near-field, signals with bipolar amplitude

range of 0.18-0.28mV that allowed both local time annotation and pacing with capture (Panel

B).

Figure 5: In a patient with history of surgical maze, two previous percutaneous left atrial

ablation procedures and mitral valve replacement, a left atrial flutter was mapped with both the

standard linear and the multielectrode catheter. A bipolar voltage map made with the linear

catheter demonstrated diffuse and homogenous scar with bipolar voltage amplitude <0.5mV,

limiting activation and entrainment mapping (Panel A right). When the multielectrode catheter

was placed at the peri-mitral area alongside the linear ablation catheter, fractionated mid diastolic

lectrorodededd cc tatatthheheh ttetet r ananananddd

e

a

gr of tissue contact force. The multielectrode catheter was positioned parallel to

n f

he m ltielectrode catheter recorded sharp near field signals ith bipolar amplit

eteeerr rr wewewew reree ppplalll cececeed ddd at a similar position at tttheheheh area of “earlr y memememeet late”. The linear

assss ppppositioned iin a pppeerpendndnddicululular orrienntaaationon to thththeee tiissueueue witthh itttss distaalaa elecctroooddde

gr offf f tititisssssssue contttacttt fffforce. ThThThThe muuultltltltieiieielelelecttttroddded cccatatatatheheheh teteteter wawawaw s positiononononedededed par llalllelll llll ttto

nel AAAA))). WhWhWhililile ththththe lililinear catthhehh ter recordeddd lllow, ffffar-fffiellllddd, sigigignananaal iwii hththh ampppliiiitutututudededede of

hh ltltiielle tct dde tathhette drd ded hha fifi leldd iig lls itithh bibi lla lplitit

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

DOI: 10.1161/CIRCEP.114.002737

26

electrograms with bipolar voltage amplitude range of 0.18-0.34mV were recorded (Panel A left).

Overdrive pacing with capture from a single electrode of the multielectrode catheter entrained

the tachycardia in orthodromic fashion and a post pacing interval that was 13ms longer than the

tachycardia cycle length. A linear ablation between the mitral valve and the left inferior

pulmonary vein terminated the tachycardia.

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from

Elad Anter, Cory M. Tschabrunn and Mark E. JosephsonCloser Interelectrode Spacing

High-Resolution Mapping of Scar-Related Atrial Arrhythmias Using Smaller Electrodes with

Print ISSN: 1941-3149. Online ISSN: 1941-3084 Copyright © 2015 American Heart Association, Inc. All rights reserved.

Dallas, TX 75231is published by the American Heart Association, 7272 Greenville Avenue,Circulation: Arrhythmia and Electrophysiology

published online March 19, 2015;Circ Arrhythm Electrophysiol. 

http://circep.ahajournals.org/content/early/2015/03/19/CIRCEP.114.002737World Wide Web at:

The online version of this article, along with updated information and services, is located on the

  http://circep.ahajournals.org//subscriptions/

is online at: Circulation: Arrhythmia and Electrophysiology Information about subscribing to Subscriptions: 

http://www.lww.com/reprints Information about reprints can be found online at: Reprints:

  document. Permissions and Rights Question and Answerinformation about this process is available in the

requested is located, click Request Permissions in the middle column of the Web page under Services. FurtherCenter, not the Editorial Office. Once the online version of the published article for which permission is being

can be obtained via RightsLink, a service of the Copyright ClearanceCirculation: Arrhythmia and Electrophysiology Requests for permissions to reproduce figures, tables, or portions of articles originally published inPermissions:

by guest on June 23, 2018http://circep.ahajournals.org/

Dow

nloaded from