Feasibility of image-based simulation to estimate ablation target in human ventricular arrhythmia

21 Pages·2013·5.01 MB·English

by  Hiroshi Ashikaga

Feasibility of image-based simulation to estimate ablation target
in human ventricular arrhythmia
Hiroshi Ashikaga, MD, PhD,*† Hermenegild Arevalo, MS,†‡ Fijoy Vadakkumpadan, PhD,†‡
RobertC.BlakeIII,MCS,†‡JasonD.Bayer,PhD,†‡SamanNazarian,MD,PhD,FHRS,*M.MuzZviman,PhD,*
Harikrishna Tandri, MD,* Ronald D. Berger, MD, PhD, FHRS,*† Hugh Calkins, MD, FHRS,*
Daniel A. Herzka, PhD,‡ Natalia A. Trayanova, PhD, FHRS,†‡ Henry R. Halperin, MD, MA, FHRS*†§
Fromthe*DivisionofCardiology,and†DepartmentofBiomedicalEngineering,JohnsHopkinsUniversitySchoolofMedicine,
Baltimore,Maryland ‡IstituteforComputationalMedicine,JohnsHopkinsUniversitySchoolofMedicine,and§TheRussellH.
Morgan Department of Radiologyand Radiological Sciences,Johns Hopkins University School of Medicine, Baltimore,
Maryland.
BACKGROUND Previous studies suggest that magnetic resonance estimatedtargetregion wasassociatedwithfailure(n¼ 1).In 1
imagingwithlategadoliniumenhancement(LGE)mayidentifyslowly (9%)case,theresultsofimage-basedsimulationandthestandard
conductingtissuesinscar-relatedventriculartachycardia(VT). approachwereinconsistent,whereablationoutsidetheestimated
targetregionwasassociatedwithacutesuccess.
OBJECTIVE Totestthefeasibilityofimage-basedsimulationbased
onLGEtoestimateablationtargetsinVT. CONCLUSIONS The image-based simulation can be used to esti-
matepotentialablationtargetsofscar-relatedVT.Theimage-based
METHODS Weconductedaretrospectivestudyin13patientswho
simulation may be a powerful noninvasive tool for preprocedural
had preablation magnetic resonance imaging for scar-related VT
planningofablationprocedurestopotentiallyreducetheprocedure
ablation. We used image-based simulation to induce VT and
timeandcomplicationrates.
estimatetargetregionsaccordingtothesimulatedVTcircuit.The
estimatedtargetregionswerecoregisteredwiththeLGEscarmap KEYWORDS Image-based simulation; Ventricular arrhythmia;
and the ablation sites from the electroanatomical map in the Catheterablation;CardiacMRI;Computersimulation
standardablationapproach.
ABBREVIATIONS3-D¼3-dimensional;ECG¼electrocardiogram/
RESULTS In image-based simulation, VT was inducible in 12 electrocardiographic; EPS ¼ electrophysiology study; HZ ¼
(92.3%) patients. All VTs showed macroreentrant propagation heterogeneouszone;ICD¼implantablecardioverter-defibrillator;
patterns,andthenarrowestwidthofestimatedtargetregionthat LGE¼lategadoliniumenhancement;LV¼leftventricular;MI¼
anablationlineshouldspantopreventVTrecurrencewas5.0(cid:1)3.4 myocardial infarction; MRI ¼ magnetic resonance imaging; SI ¼
mm.Of11patientswhounderwentablation,theresultsofimage- signalintensity;VT¼ventriculartachycardia
basedsimulation and thestandardapproach were consistent in 9
(82%)patients,whereablationwithintheestimatedtargetregion (HeartRhythm2013;10:1109–1116)I2013HeartRhythmSociety.
wasassociatedwithacutesuccess(n¼8)andablationoutsidethe Allrightsreserved.
Introduction VT critically depends on the regions of relatively slow
conductionoftheimpulsethatallowsothersegmentsofthe
Scar-related ventricular tachycardia (VT) most commonly
heart to recover excitability.1,2 The current approach of
results from healed myocardial infarction (MI) and is
therapeutic ablation is to use invasive catheters to “search
frequently refractory to medical therapy. Perpetuation of
and destroy” this slowly conducting tissue. However, this
approach is time-consuming and often inaccurate, because
A part of this study was presented at the Melvin Judkins Young VT cannot always be inducible during electrophysiology
InvestigatorAwardCompetitionin2011ScientificSessionsoftheAmerican
study(EPS)anditmaybehemodynamicallyunstable.These
HeartAssociationinOrlando,FL.DrTrayanovaandDrBlakearemembers
of the scientific advisory board of CardioSolv, LLC. This study was not limitationsresultinlongproceduretime,highcomplications
supported by CardioSolv, LLC. This study was supported by National rates, and highrecurrencerates.3–5
Institutes of Health grants R01-HL094610 (to Dr Halperin) and R01- Previous studies suggest that magnetic resonance imaging
HL082729 (to Dr Trayanova). Address reprint requests and (MRI) with late gadolinium enhancement (LGE) may identify
correspondence: Dr Hiroshi Ashikaga, Cardiac Arrhythmia Service,
theseslowlyconductingtissues.Theheterogeneouszone(HZ),
Division of Cardiology, Johns Hopkins University School of Medicine,
defined as a highly complex mixture of scar and normal-
600 N Wolfe St, Carnegie 568, Baltimore, MD 21287. E-mail address:
[email protected]. appearingtissueintransitionbetweenthescarandthepreserved
1547-5271/$-seefrontmatterB2013HeartRhythmSociety.Allrightsreserved. http://dx.doi.org/10.1016/j.hrthm.2013.04.015
1110 Heart Rhythm, Vol 10, No8, August 2013
normal tissues, is a structural basis of slowly conducting patientsunderwentcardiacMRIwithLGEwitha1.5-Tscanner
tissue.1,6TheHZiscommonlyfoundintheinfarctborderzone. (Avanto,SiemensMedicalSolutions,Erlangen,Germany).10
Wehavepreviouslydemonstratedthat(1)MRIwithLGEcan
identify the HZ, (2) the LGE-derived HZ contains regions of EPS and ablation
abnormal electrical conduction, represented by fractionated
AllthepatientsunderwentthestandardEPSandablationof
electrograms, which are standard targets for ablation, (3) the
scar-relatedVTundertheguidanceofa3-dimensional(3-D)
HZcanbefoundinthepathwaywithintheVTcircuit,and(4)
electroanatomicalmappingsystem(CARTO,BiosenseWeb-
successfulVTablationtargetsarelocalizedwithintheHZ,and ster,DiamondBar,CA).Thestandardsubstratemodification
incompleteablationoftheHZisassociatedwithrecurrence.7–9
with radiofrequency ablation was performed during sinus
OthersalsofoundthattheLGE-derivedHZvolumeisaclinical
rhythm. After ablation, programmed stimulation was repe-
predictorofVTanddeath.10–12 ated. Acute success was defined as the inability to induce
Onthebasisoftheseresults,wehypothesizedthattheHZ
clinical VT at the end of the procedure. If nonclinical VT
identified noninvasively by LGE contains the slowly con-
morphologies were inducible, those were also ablated.
ducting tissue that is the critical part of the VT circuits. To
identifythecriticalcomponentsoftheHZthatparticipatein
Image processing
the VT circuits, we can use a patient-specific, image-based
A finite element mesh of the heart was created from the LGE
computational simulation. We conducted a retrospective
images for computer simulation. The scar was defined as the
study to evaluate the feasibility of image-based simulation
myocardium with signal intensity (SI) greater than 50% of the
to estimate the potential ablation targets in scar-related VT.
maximalSIwithinthemyocardium,andtheHZwasdefinedas
the myocardium with SI greater than the peak SI in the remote
Methods
normalmyocardiumbutlessthan50%ofthemaximalSIwithin
The study workflow is shown in Figure 1. This study was the myocardium.10 Myofiber orientation in the ventricles was
retrospective but was conducted in a double-blind fashion, estimatedonthebasisofamodificationofarule-basedmethod13
wheretheprocedureoperatorswereblindedtothesimulation wherethetransmuralmyofiberdirectionwasassignedasalinear
results and those who performed image processing and functionofthedistancefromtheendocardiumtotheepicardium,
simulation were blinded to the clinical results. Please refer from þ601 to −601, respectively, with reference to the circum-
to the Online Supplement Material for detailed methods. ferentialdirection(Figure1).14Thetransmuralmyolaminarsheet
directionwasfixedat−301withreferencetotheradialdirection.15
Study population
Weretrospectivelyevaluatedthepatientswhowerereferredfor Computer simulation
catheter ablation of VT between July 2006 and April 2011. We used a biophysically detailed model of whole heart
Patients were included if preablation MRI with LGE showed electrophysiology to simulate VT. Ventricular tissue was
myocardialscar,andpatientswereexcludedifpreablationMRI modeled as monodomain, and the passive tissue properties
showed any artifacts within the heart from an implantable anisotropic.Thescarwasmodeledasaninsulator.Membrane
cardioverter-defibrillator (ICD) and/or the ICD leads. The kinetics of the noninfarct tissue was represented by the ten
Figure1 Studyworkflow.Thepatientsreferredforventriculartachycardia(VT)ablation(n¼13)underwentpreablationmagneticresonanceimaging(MRI),
whichwasprocessedtoprovidetheheartandinfarctgeometry(scar:red;HZ:yellow)andestimatedmyofiberorientation(“Image-BasedSimulation”).These
geometricaldatawereincorporatedintomathematicalsimulationofVTtoestimatepotentialtargetregions.Patientsunderwentaninvasiveelectrophysiology
study(EPS;n¼13)andablation(“StandardApproach”;n¼11)byusingbiplaneX-rayfluoroscopyand3-dimensional(3-D)electroanatomicalmapping
(CARTO).Ablationlesionlocationswererecordedin3-Dspaceandwerecomparedwiththetargetregionsestimatedbysimulation.Thestudywasretrospective
butwasconductedinadouble-blindfashion,wheretheprocedureoperatorwasblindedtothesimulationresults,andthepersonwhoperformedimageprocessing
andsimulationwasblindedtotheclinicalresults.LAO¼leftanterioroblique;RAO¼rightanterioroblique.
Ashikaga etal Image-Based Simulation of Ventricular Arrhythmia 1111
Tusschermodelofthehumanventriculartissue.16Thesame Table 1). The clinical VT morphology was inducible in all
membranemodelwasalsomodifiedtorepresenttheelectro- patients. All VT morphologies were hemodynamically
physiology of HZ cells. All simulations were performed by unstable,andthereforeablationwasperformedduringsinus
using the software package CARP (CardioSolv, LLC) on a rhythm in all the cases. Catheter ablation was performed in
parallel computing platform, a 2000-core Linux cluster; the 11(84.6%)patients,ofwhichacutesuccesswasachievedin
numerical methodology has been described in previous 10 (90.9%) patients. The extent of ablation lesions was
publications.17–19A500-msepisodeofactivityinthemulti- recorded in a 3-D electroanatomical map. The remaining 2
scalemonodomainmodelwithagridof5.4millionelements (15.4%) patients underwent the EPS without catheter abla-
typicallytook3hourstorunon15nodes. tion. The procedure time was 393 (cid:1) 152minutes.
Statistical analysis
Continuous variables are presented as means (cid:1) SD and Image-based simulation
categoricalvariablesasnumbersandpercentages.Studentpaired VT was inducible in image-based simulation in 12 (92.3%)
t tests were performed to compare the extent of the estimated patients (see Online Supplemental Videos 1–12). All indu-
target region. A P value of o.05 is considered statistically cible VTs showed macroreentrant propagation patterns
significant. Statistical analysis was performed by using the (Table 2). VT circuits were analyzed to identify the critical
MATLABStatisticalToolbox(MathWorks,Inc,Natick,MA). pathway segments circumscribed by lines of condu-
ction block.
In 5 patients, the circuits were of the figure-of-eight
Results
reentry pattern, where 2 counterrotating waves coexist at a
Patients
relatively short distance from each other. The central
In 34 patients referred for catheter ablation of VT, preablation
common pathway, or the isthmus, of the 2 counterrotating
MRI with LGE showed myocardial scar. Twenty-one (61.8%) waveswaslocatedovertheHZorthesuperficiallayerofthe
patientswereexcludedbecauseofthepresenceofimageartifact
viable myocardium over the scar. In this typeof circuit,the
withintheheart,regardlessofthesizeandthelocation,resulting
target region was estimated to be an area bordered by 2
from an ICD and/or the ICD leads. The remaining 13 (38.2%)
facing lines of conduction block that compose the isthmus
patientswereincludedforanalysis(Table1).Theagewas65(cid:1)
(Figure2,greenareaintheSimulationcolumn).Anablation
9 years, and the left ventricular ejection fraction was 42% (cid:1)
linethatspansbetweenthe2facinglinesofconductionblock
16%.Two(15.4%)patientswerewomen,and2(15.4%)patients
is expected to prevent VT recurrence, and the minimum
had an ICD. Nine (69.2%) patients had underlying coronary
length of this hypothetical ablation line (ie, narrowest
arterydisease.Allpatients(n¼13)underwentpreablationMRI isthmus width) was quantified.
and an EPS. Preablation MRI showed that the infarct size was
In7patients,thecircuitswereoftheunidirectionalcircus
24%(cid:1)15%oftheleftventricular(LV)myocardium(scar11%
movement reentry pattern. In this type of circuit, the target
(cid:1)7%andHZ13%(cid:1)10%).TheHZsizewas54%(cid:1)19%of
regionwasestimatedtobeatriangularareathatconnectsone
the infarct. Preablation MRI was performed 100 (cid:1) 285 days
end of the line of conduction block that is closer to an
beforetheEPS(range0–1041days).
adjacentanatomicalbarrier(eg,mitralannulus).Anablation
linethatextendstheexistinglineofconductionblocktothe
Standard approach anatomicalbarrierisexpectedtopreventVTrecurrence,and
All patients had 1 clinical VT morphology, and the 12-lead the minimum length of this hypothetical ablation line was
electrocardiogram(ECG)ofclinicalVTwasavailableforall quantified.
the cases before the EPS. The number of inducible VT In 1 patient (7.7%), VT was not inducible in simulation.
morphologies at the time of EPS was 2 (cid:1) 1 (range 1–4; This case was a repeat ablation where the patient had
Table1 Baselinecharacteristics
Patient Figure Age(y) Sex Heartdisease EF(%) ICD Scar ClinicalVT InducibleVT
1 3A 68 M CAD 60 No AntSepLat 1 3
2 Supp1B 52 M None 55 No Inf 1 1
3 2A 71 M CAD 35 No Inf 1 1
4 4C 62 M AR 55 No Sep 1 4
5 Supp1C 64 F None 81 No RVseptum 1 1
6 4B 47 F Sarcoidosis 34 No Sep 1 1
7 2B 56 M CAD 30 Yes Inf 1 3
8 4A 72 M CAD 29 No Inf 1 3
9 2C 73 M CAD 33 Yes InfSep 1 3
10 Supp1A 78 M CAD 32 No AntLat 1 1
11 Supp2 66 M CAD 31 No Lat 1 1
12 3B 61 M CAD 27 No InfLat 1 1
13 3C 75 M CAD 45 No SepInf 1 1
Ant¼anteriorwall;AR¼aorticregurgitation;CAD¼coronaryarterydisease;EF¼ejectionfraction;ICD¼implantablecardioverter-defibrillator;Inf¼
inferiorwall;Lat¼lateralwall;RV¼rightventricular;Sep¼septalwall;Supp¼supplemental;VT¼ventriculartachycardia.
1112 Heart Rhythm, Vol 10, No8, August 2013
Table2 AnalysisofVTcircuitsandablation
Image-basedsimulation Standardapproach
Patient Figure Reentrypattern Narrowesttargetwidth(mm) Ablationinestimatedtargetregion Acutesuccess Consistency
1 3A Figure-of-eight 5.1 Yes Yes Yes
2 Supp1B Circusmovement 7.9 N/A(EPSonly)
3 2A Figure-of-eight 1.7 Yes Yes Yes
4 4C Circusmovement 2.1 Yes Yes Yes
5 Supp1C Noninducible N/A Yes No
6 4B Circusmovement 5.7 Yes Yes Yes
7 2B Figure-of-eight 2.0 Yes Yes Yes
8 4A Circusmovement 4.7 Yes Yes Yes
9 2C Figure-of-eight 2.0 Yes Yes Yes
10 Supp1A Figure-of-eight 12.1 N/A(EPSonly)
11 Supp2 Circusmovement 9.7 No No Yes
12 3B Circusmovement 3.6 Yes Yes Yes
1.6 Yes
13 3C Circusmovement 6.4 No Yes No
Mean(cid:1)SD 5.0(cid:1)3.4 9of11¼82% 10of11¼91% 9of11¼82%
EPS¼electrophysiologystudy;N/A¼notapplicable;Supp¼supplemental;VT¼ventriculartachycardia.
undergoneapreviousablationattemptforafocal,non-scar- tothemitralannulus(minimumlength¼5.7mm)andeach
related VT(see Online Supplemental Figure 1C). ablation usually creates lesions of at least 5–6 mm in
diameter, these 3 lesions likely created a line of block with
ablation in the target region (see the green area in the
Comparison Estimated target region column).
Thecomparisonbetweentheimage-basedsimulationandthe Patient 11 had an MI in the lateral apex (Online
standardapproachwasavailablein10patients.Forexample, Supplemental Figure 2, MRI column). In simulation, the
patient3hadalargeinferiorMI(Figure2A,theMRIcolumn). lineofconductionblockwaslocated intheapicalborderof
Thesimulationshowedpropagationofexcitationwavefronts the MI (see the blue line in Simulation and MRI columns).
through the figure-of-eight reentry circuit over the basal The target region was estimated to be a triangular area that
inferior region, where electrical activation spread longitudi- connectstheposteriorendofthelineofconductionblockto
nally over the isthmus toward the base, split into 2 opposite themitralannulus(seethegreenareaintheEstimatedtarget
lateral directions, and then returned longitudinally and api- region column). This area was located in the viable layer
callytotheotherendoftheisthmus(seegreenarrowsinthe over the posterior border of the MI. Only 1 ablation lesion
Simulation column). Simulation estimated that the potential fellintheestimatedtargetregion(seetheyellowcircleinthe
targetregiontobetheisthmusborderedbythe2facinglines Estimatedtargetregioncolumn),andtheminimumlengthof
ofconductionblockintheendocardialviablelayerinthebasal possibleablationlinewasrelativelylong(length¼9.7mm).
inferior region (seegreen area inthe Estimated target region Thus,itisunlikely thatthisablationlesion created aline of
column). The narrowest width of the isthmus was 1.7 mm. blockinthetargetregion(seethegreenareaintheEstimated
This VT circuit was consistent with the 12-lead ECG of the targetregioncolumn).Infact,thiscasedidnotachieveacute
clinical VT induced in the EPS (see the Electrophysiology success by using the standard approach. Therefore, the
studycolumn).ThecoregistrationoftheCARTOmap(seethe results of the image-based simulation and the standard
Ablation column) and simulation demonstrates that most of approach were determined to beconsistent.
the radiofrequency ablation lesions fell within the estimated Patient 13 had an extensive MI in the septum and the
targetregion(seeyellowcirclesintheEstimatedtargetregion inferiorregion(Figure3C,MRIcolumn).Insimulation,the
column). In this case, the results of image-based simulation target region was estimated to be a triangular area that
andthestandardapproachweredeterminedtobeconsistent. connectsthesuperiorendofthelineofconductionblockto
Patient6hadalargeareaofscarandHZintheseptumdue themitralannulus(seethegreenareaintheEstimatedtarget
tocardiacsarcoidosis(Figure4B,MRIcolumn).Simulation region column). This area was located in the superficial
showed a unidirectional circus movement reentry (see the viable layer over the scar in the posterior septum. Multiple
greenarrowsintheSimulationcolumn),andthetargetregion ablation lesions were created in the standard approach, but
was estimated to be a triangular area that connects the nonefellintheestimatedtargetregion(seedashedredcircles
superior end of the line of conduction block to the mitral in the Estimated target region column). However, clinically
annulus (see the green area in the Estimated target region this case achieved acute success. In this case, the results of
column).Thisareawaslocatedinthesuperficialviablelayer theimage-basedsimulation andthestandardapproachwere
overthescarintheposteriorseptum.Threeablationlesions determined to beinconsistent.
fell in the estimated target region (see yellow circles in the In summary, (1) based on image-based simulation, the
Estimatedtargetregioncolumn).Theselesionsdonotappear narrowest width of the target region that an ablation line
to span the target region by themselves. However, because shouldspantopreventVTrecurrencewas5.0(cid:1)3.4mm;(2)
oneendofthelineofconductionblockwasrelativelyclose in 9 of 11 (82%) cases, the results of the image-based
Ashikaga etal Image-Based Simulation of Ventricular Arrhythmia 1113
Figure2 Comparisonbetweenimage-basedsimulationandstandardapproach.Eachrowrepresentsadifferentpatient(A–C).TheSimulationcolumnshows
ventriculartachycardia(VT)withanisochronemapofactivationbasedonimage-basedsimulation.Greenarrowsindicatewavepropagationofmacroreentry
circuits.Linesofconductionblockareindicatedinblue.TheElectrophysiologystudycolumnshowsthe12-leadelectrocardiogram(ECG)ofinducibleVTsfrom
thestandardapproach.TheAblationcolumnshowsthe3-dimensionalCARTOmapwithacolor-codedvoltagemap(normalmyocardium:purple;infarctborder
zone:blue,green,andyellow;scar:red)fromthestandardapproach.Redcirclesrepresenttheablationsites.Thesizeofthecirclesdoesnotreflectthesizeof
ablationlesions.Themagneticresonanceimaging(MRI)columnshowspreablationMRIwithinfarctgeometry(scar:orange;heterogeneouszone:yellow;
noninfarctmyocardium:gray).Thelinesofconductionblock(bluelines)fromtheimage-basedsimulationandtheablationsites(redcircles)fromthestandard
approacharecoregisteredontheheartgeometry.TheEstimatedtargetregioncolumnshowsapotentialtargetregion(greenarea)estimatedfromtheimage-based
simulation.Theshortestpossiblelineofablationthatspansthetargetregion(ie,narrowestwidthoftheisthmus)isshownincyancolor.Theablationsitesthatfell
withintheestimatedablationtarget(greenarea)areindicatedbyyellowcircles.All3simulationresultsinthisfigure(patientsA–C)showafigure-of-eight
patternandareconsistentwiththe12-leadECGoftheclinicalVT.Thescalesofthe12-leadECGintheElectrophysiologystudycolumnis100mm/s(patientsA
andB)and25mm/s(patientC).
simulationandthestandardapproachwereconsistent,where Discussion
ablation within the estimated target region was associated Image-based simulation in electrophysiology has been used
withacutesuccess(n¼8)andablationoutsidetheestimated inanimalmodels,20–23butthisisthefirststudytoapplythe
target region was associated with failure (n ¼ 1); (3) in 1 image-based simulation to reproduction of clinical arrhyth-
(9%)case,VTwasnotinducibleinsimulation.Thiscasewas mia andestimation of ablation targets in human patients.
arepeatablationwherethepatienthadundergoneaprevious
ablation attempt for a focal, non-scar-related VT; (4) in 1
(9%)case,theresultsoftheimage-basedsimulationandthe Feasibility
standardapproachwereinconsistent,whereablationoutside The comparison between the image-based simulation and the
the estimated target region was associated with acute standard approach showed that these 2 approaches are highly
success. The resultsare summarized in Table 2. consistent with each other (82%; Table 2). This indicates that
1114 Heart Rhythm, Vol 10, No8, August 2013
Figure 3 Comparison between image-based simulation and standard approach (continued). The figure structure is the same as in Figure 2. The first 2
simulationresultsinthisfigure(patientsAandB)showafigure-of-eightpattern,andthelastsimulationresult(patientC)showaunidirectionalcircusmovement
pattern.Allsimulationresultsareconsistentwiththe12-leadelectrocardiogram(ECG)oftheclinicalventriculartachycardia(VT).Thescaleofthe12-leadECG
intheElectrophysiologystudycolumnis100mm/s(patientsA–C).MRI¼magneticresonanceimaging.
image-based simulation can be used to estimate potential Furthermore, some lines or surfaces of conduction block may
ablationtargets.Oursimulationresultsindicatethatthenarrow- purely be a mid-myocardial structure hidden from both the
estwidthofthetargetregionthatanablationlineshouldspanto endocardial and epicardial surfaces. Such a mid-myocardial
prevent VT recurrence was relatively small (5.0 (cid:1) 3.4 mm; structurecancreatetargetregionsinthemid-myocardium.This
Table 2). The preprocedural estimation of the location and the mayaccountforthecaseofpatient13(Figure3C),wherethe
sizeofthetargetregionbyimage-basedsimulationwouldlikely image-based simulation and the standard approach showed
helpreducetheproceduretime. inconsistentresults.Inthiscase,acutesuccesswasachievedbut
Inthisstudy,ablationwasperformedontheLVendocar- ablation was outside the target regions estimated from VT
dium and achieved acute success in 91% of the cases. circuits on the heart surfaces. These ablation sites may have
However, in most cases the target region was estimated to destroyed the hidden mid-myocardial target region that is not
reside on the opposite side of the wall, including the LV evidentfromtheheartsurfaces.Infact,thescarandtheHZin
epicardiumortherightventricularseptum.Therearepossible theseptuminthispatientweremostlyinthemid-myocardium.
mechanismstoexplainthisapparentlycontradictoryresult. Thisexplainswhytheendocardialvoltagemapofmostofthe
One possible explanation is that the lines of conduction VT circuit region shows normal voltage (see pink area in the
blockandthetargetregionsareinfact3-Dstructureswithinthe Ablationcolumn).
myocardium and ablation on the LV endocardium may have Another explanation is that although ablation was per-
destroyed the hidden target region in the mid-myocardium. formed from the opposite side of the wall, it created
Ashikaga etal Image-Based Simulation of Ventricular Arrhythmia 1115
Figure4 Comparisonbetweenimage-basedsimulationandstandardapproach(continued).ThefigurestructureisthesameasinFigure2.All3simulationresultsin
thisfigure(patientsA–C)showaunidirectionalcircusmovementpatternandareconsistentwiththe12-leadelectrocardiogram(ECG)oftheclinicalventricular
tachycardia(VT).Thescaleofthe12-leadECGintheElectrophysiologystudycolumnis100mm/s(patientsA–C).MRI¼magneticresonanceimaging.
sufficientlylargephysicaldisruptionofthemyocardialtissue simulationbecausethecriticalpartofthereentryVTcircuits
for acute success. For example, a standard open-irrigated wasnotintuitivelyidentifiablebysimplyreviewingtheMR
3.5-mm-tip ablation catheter used in most of the cases can images with scar andHZ tissues in ourcases.
create a spherical lesion of as large as 5–6mm in diameter.
Comparison with other advanced mapping systems
Mechanistic implications Theadvantageofourimage-basedsimulationsystemisthat
Contrary to our hypothesis, we found that the slowly it is completely noninvasive, whereas the standard contact
conducting tissue that is the critical part of the reentry VT (eg, CARTO, NavX [St Jude Medical, St Paul, MN]) and
circuits was not limited to the HZ but also localized in the noncontact (EnSite [St Jude Medical]) electroanatomical
superficial rim of the scar. This result is indeed consistent mapping systems and the multielectrode basket catheter
with our previous report, demonstrating that the isthmus of system (Constellation [Boston Scientific]) require invasive
the reentry VT circuits was located either within the HZ or catheter insertion at the time of the EPS. The noninvasive
overthesuperficialrimofthescar.7Themechanismofslow nature of our system allows preprocedural diagnosis and
conductioninthesuperficialrimofthescarislikelyduetoa planning of ablation. Our system provides complementary
suddenincreaseintheconvexityoftheelectricalwave-front advantages over ECG imaging (CardioInsight),25 which is
curvature and the resulting impedance mismatch caused by anotheradvancednoninvasivemappingsystemthathasbeen
sharp scar thickness transition at the infarct border zone.24 gathering attention. An advantage of our technique over
These findings highlight the utility of image-based ECG imaging is that the target arrhythmia does not
1116 Heart Rhythm, Vol 10, No8, August 2013
necessarily needtobeinducibleatthetimeofpreprocedure 3. Stevenson WG,Wilber DJ, Natale A, etal. Irrigated radiofrequency catheter
planning or at the invasive EPS, because the targets can be ablationguidedbyelectroanatomicmappingforrecurrentventriculartachycardia
identified in simulation. This advantage would address aftermyocardialinfarction:themulticenterthermocoolventriculartachycardia
ablationtrial.Circulation2008;118:2773–2782.
therapeutic approaches to the arrhythmias that tend to
4. TannerH,HindricksG,VolkmerM,etal.Catheterablationofrecurrentscar-
become noninducible owing to sedation or general anesthe- related ventricular tachycardia using electroanatomical mapping and irrigated
sia at the time of the EPS. ablation technology: results of the prospective multicenter Euro-VT-study.
JCardiovascElectrophysiol2010;21:47–53.
5. CalkinsH,EpsteinA,PackerD,etal.RFMultiCenterInvestigatorsGroup.
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Despite promising results, in this small feasibility study the diseaseusingcooledradiofrequencyenergy:resultsofaprospectivemulticenter
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accuracy of target estimation could not be precisely quanti-
6. KaragueuzianHS,FenoglioJJJr,Weiss MB,WitAL.Protracted ventricular
fied,becauseitwasnotpossibletoretrospectivelydetermine tachycardiainducedbyprematurestimulationofthecanineheartaftercoronary
which ablation lesion(s) was critical in preventing VT arteryocclusionandreperfusion.CircRes1979;44:833–846.
7. Ashikaga H, Sasano T, Dong J, et al. Magnetic resonance-based anatomical
recurrence.Thepatientswerehighlyselected,andthesample
analysisofscar-relatedventriculartachycardia:implicationsforcatheterablation.
sizewassmall.However,thestudyparticipantsrepresentthe CircRes2007;101:939–947.
prototypical patient population who are referred for scar- 8. AshikagaH,MickelsenSR,EnnisDB,etal.Electromechanicalanalysisofinfarct
related VT ablation (Table 1).3 Because tissue properties in borderzoneinchronicmyocardialinfarction.AmJPhysiolHeartCircPhysiol
2005;289:H1099–H1105.
LGEwereusedasasurrogateforelectricalpropertiesofthe
9. Estner HL, Herzka DA, Castro V, et al. Heterogeneous zones in magnet
myocardium,theimage-basedsimulationisnotapplicableto resonance images are the critical areas for ventricular tachycardia and for
idiopathic VT or ventricular arrhythmias without distinct successfulablation.Circulation2009;120:S690.
scar identified by LGE. Because all the VTs were hemody- 10. SrecshomnaidntceA,iAmzaegviendgoiCdFen,tCifiheesngeAnh,aentcael.dIncfaarrcdtiaticssuarerhhyettehrmogiaenseuitsycebpytimbialigtnyetiinc
namically unstable, we were not able to validate the patientswithleftventriculardysfunction.Circulation2007;115:2006–2014.
simulated VT circuits against the activation maps from the 11. YanAT,ShayneAJ,BrownKA,etal.Characterizationoftheperi-infarctzoneby
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orientation within the nonscar myocardium is preserved
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14. Streeter DD Jr, Spotnitz HM, Patel DP, Ross J Jr, Sonnenblick EH. Fiber
the location of target regionsin this patient population.
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Conclusion 15. LeGrice IJ, Smaill BH, Chai LZ, Edgar SG, Gavin JB, Hunter PJ. Laminar
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Image-based simulation can be used to estimate potential architectureinthedog.AmJPhysiol1995;269:H571–H582.
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ventriculartissue.AmJPhysiol2004;286:H1573–H1589.
may be a powerful noninvasive tool for pre-procedural
17. Plank G, Zhou L, Greenstein JL, et al. From mitochondrial ion channels to
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arrhythmiasintheheart:computationaltechniquestobridgethespatio-temporal
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electricalactivityincardiactissue.JElectrocardiol2003;36:69–74.
Acknowledgments
19. VigmondEJ,WeberdosSantosR,PrasslAJ,DeoM,PlankG.Solversforthe
We thank Rozann Hansford for excellent patient care and cardiacbidomainequations.ProgrBiophysMoleBiol2008;96:3–18.
20. Ng J, Jacobson JT, Ng JK, et al. Virtual electrophysiological study in a 3-
monitoringduringpreablationMRIscanning.Wealsothank
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Supplementary data
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Ashikaga et al., Image-Based Simulation of Ventricular Arrhythmia

Detailed Methods
The study workflow is shown in Figure 1. This study was retrospective but was
conducted in a double-blind fashion, where the procedure operators were blinded to the
simulation results, and those who performed image processing and simulation were blinded to
the clinical results.
Study Population. We retrospectively evaluated the medical records of the patients who
were referred to the Johns Hopkins Hospital between July 2006 and April 2011 for catheter
ablation of VT. The study was approved by the Institutional Review Board of the Johns Hopkins
Medical Institutions. Patients were included if the pre-ablation MRI with LGE showed
myocardial scar. To avoid any possibility of confounding the data, patients were excluded if the
pre-ablation MRI showed any artifacts within the heart, regardless of the size and the location,
from an implantable cardioverter defibrillator (ICD) and/or the ICD leads.
Pre-Ablation MRI. Our MRI protocol for LGE has been described previously1. Briefly,
the patients underwent cardiac MRI with LGE with a 1.5-T scanner (Avanto, Siemens Medical
Solutions) with the standard 6-element cardiac phased-array receiver coil and the spine coil. Ten
to 12 contiguous short-axis slices were prescribed to cover the entire left ventricle (LV). LGE
images were acquired 15 to 30 minutes after an intravenous injection of a contrast agent
(Magnevist, gadolinium diethylenetriaminepentacetate <Gd-DTPA>, Berlex) at 0.2 mmol/kg
with a standard non-phase-sensitive inversion recovery sequence. Representative imaging
parameters were as follows: repetition time 1 heartbeat (~ 700-1000 ms), echo time 3.32 ms, in-
plane spatial resolution 1.5-1.9 mm, 8-mm slice thickness, 0-2-mm gap, inversion time 175 to
280 ms (adjusted to null the signal of normal myocardium), flip angle 25° and a gradient recalled
echo (GRE) readout. Each image acquisition was ECG gated, and the image was acquired during
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Ashikaga et al., Image-Based Simulation of Ventricular Arrhythmia

a single, typically end-expiration, breath hold. If the patient had an ICD, monitoring and
tachyarrhythmia therapies (anti-tachycardia pacing/defibrillation) were turned off during the
scanning2, 3.
Electrophysiology Study and Mapping. Intracardiac electrograms were filtered at 50 to
500 Hz. Quadripolar electrode catheters (5 Fr) were introduced into the right femoral vein and
advanced to the high right atrium, the His position, and the right ventricular (RV) apex.
Programmed RV stimulation was performed in all patients with 1 to 3 extrastimuli to induce VT.
Three-dimensional (3-D) electroanatomical mapping (CARTO, Biosense Webster, Diamond Bar,
California) of the LV was performed with either a 4-mm tip ablation catheter (Navistar, Biosense
Webster) or a 3.5-mm tip, open-irrigation ablation catheter (Thermocool, Biosense Webster).
The ablation catheter was introduced to the LV by a transseptal approach via a femoral vein,
and/or by a retrograde aortic approach via a femoral artery. A voltage map was generated during
sinus rhythm, followed by activation. All VTs studied were hemodynamically unstable,
precluding use of entrainment or activation mapping. An isthmus, or a central common pathway,
of the VT circuit was identified by pace-mapping, where a match of the QRS morphology
between the pace map and the VT was achieved. The location within the isthmus was estimated
by the interval between the pacing stimulus and the onset of QRS complex on the surface ECG.
Low voltage was defined as bipolar voltage amplitude ≤1.5 mV, and scar as bipolar voltage
amplitude ≤0.5 mV4. Intraprocedural anticoagulation was achieved by multiple bolus injection of
heparin to maintain an activated clotting time between 350 and 400 sec.
Ablation. RF energy was delivered at sites of origin as determined by the
electrophysiology study and mapping. For non-irrigated catheters, the target temperature was set
to 60°C; for irrigated tip catheters, the initial power setting was 30 W; applications of RF energy
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