Role of transthoracic left atrial appendage wall motion velocity in patients with persistent atrial fibrillation and a low CHADS2 score

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ContentslistsavailableatSciVerseScienceDirect

Journal

of

Cardiology

j our na l h o me p ag e :w w w . e l s e v i e r . c o m / l o c at e / j j c c

Original

article

Role

of

transthoracic

left

atrial

appendage

wall

motion

velocity

in

patients

with

persistent

atrial

ﬁbrillation

and

a

low

CHADS2

score

Naoyasu

Yoshida

(PhD)

a,∗

_,

_Mitsunori

_Okamoto

_(MD,

_FJCC)

b

_,

_Hidekazu

_Hirao

_(MD)

b

_,

Kiyomi

Nanba

(MSc)

a

_,

_Hiroki

_Kinoshita

_(MD)

b

_,

_Hiroya

_Matsumura

_(MD)

b

_,

Yukihiro

Fukuda

(MD)

b

_{, Hironori}

_Ueda

_(MD,

_FJCC)

b

a_{Echocardiography}_Division,_Department_of_Laboratory_Medicine,_Hiroshima_Prefectural_Hospital,_Hiroshima,_Japan b_Department_of_Cardiology,_Hiroshima_Prefectural_Hospital,_Hiroshima,_Japan

a

r

t

i

c

l

e

i

n

f

o

Articlehistory: Received1March2012

Receivedinrevisedform17April2012 Accepted8May2012

Availableonline26June2012 Keywords:

Leftatrialfunction

TissueDopplerechocardiography Cerebralembolism

Atrialﬁbrillation CHADS2score

a

b

s

t

r

a

c

t

Backgroundandpurpose:Thromboembolicriskhasbeenexaminedbysemi-invasivetransesophageal echocardiography.Weassessedtheriskofthrombogenesisinpatientswithpersistentatrialﬁbrillation (AF)noninvasivelybyusingtransthoracictissueDopplerechocardiography(TDE)inrelationtoalow CHADS2score.

Methods:EightypatientswithpersistentAFunderwentbothtransthoracicandtransesophageal echocar-diography.Peakleftatrialappendage(LAA),wallmotionvelocity(WV)duringLAAcontractionwas measuredbytransthoracicandtransesophagealTDE.LAAﬂowvelocitywasalsodeterminedby trans-esophagealechocardiography.

Results:TransthoracicLAAWVcouldbemeasuredin78ofthe80patients,andthevalueswereclosely cor-relatedwithtransesophagealTDEvalues(r=0.98)andwithtransesophagealLAAflowvelocity(r=0.82). TransthoracicLAAWVwassignificantlylowerwithincreasingspontaneousechocontrast(SEC)severity (severeSEC,mildSEC,noSEC:5.7±2.4,10.2±3.3,and14.5±5.5cm/s,respectively).SevereSECwas notedin31of61patientswithaCHADS2score≤2,in19of46patientswithaCHADS2score≤1andin6 of21patientswithaCHADS2score=0.FordiagnosingsevereSEC,atransthoracicLAAWV<10cm/shad asensitivityof81%andspecificityof92%inthepatientswithaCHADS2score≤2,asensitivityof74%and specificityof91%inthepatientswithaCHADS2score≤1andasensitivityof44%andspecificityof83% inthepatientswithaCHADS2score=0.

Conclusions:AtransthoracicLAAWV<10cm/sinpersistentAFpatientswithalowCHADS2scoremaybea veryspeciﬁcdiagnostictoolforevaluatingsevereSEC,oneofthehighriskfactorsforthromboembolism. ©2012JapaneseCollegeofCardiology.PublishedbyElsevierLtd.Allrightsreserved.

Introduction

Cerebral infarction induced by cardiogenic embolism is observedin 13–34%of strokepatients[1].Cardiogeniccerebral embolismismostfrequentlycausedbyatrialfibrillation(AF).The reducedleftatrialfunctioninpatientswithAFmayresultin throm-busformationintheleftatrialappendage(LAA).Thefunctional parametersoftheLAAsuchasflowvelocity,fractionalchange dur-ingatrialcontraction,andspontaneousechocontrast(SEC)have beenpreviouslyassessed by transesophagealechocardiography. AnLAAflowvelocityof<20cm/sandprominentSECarehigh-risk

∗ _{Corresponding}_author_at: _{Echocardiography}_Division,_Department_of

Labo-ratoryMedicine,HiroshimaPrefecturalHospital,1-5-54Ujinakanda,Minami-Ku, Hiroshima734-8530,Japan.Tel.:+822541818;fax:+822530659.

E-mailaddress:n yoshida0210@ybb.ne.jp(N.Yoshida).

factors for cerebral embolism [2,3]. LAA wall motion velocity (LAAWV),whichisanindicatorofLAAfunctionand thromboge-nesisrisk,hasbeenmeasuredbytransesophagealtissueDoppler echocardiography (TDE) [4–9]. However, since this is a semi-invasive method, its application as a screening tool is limited. Therefore, analternativenoninvasive methodforassessing LAA functionisrequired.

Recentdevelopments in transthoracicechocardiography and newtechnologyhavefacilitated theevaluationofthesize,ﬂow velocities,andemptyingfractionoftheLAA[10–12].Moreover, LAAfunctioninpatientswithsinusrhythmandAFhasbeen deter-minedbytransthoracicTDE.TransthoracicTDEcanpredicttherisk ofthromboembolisminpatientswithahistoryofstrokeor tran-sientischemicattack[13–15].Ontheotherhand,theCHADS2score isawidelyusedclinicalindexforevaluatingtheriskof thromboem-bolismand initiating anticoagulanttherapy in patientswithAF

[16].Recently,CHA(2)DS(2)-VAScscoreshavebeenalsoproposed

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Table1

Patientcharacteristics.

Variables Atrialﬁbrillationpatients

Number 78

Men 56

Age(years) 69±9

HT 24

DM 14

Congestiveheartfailure 26

Warfarin 25 CHADS2score≥3 17 CHADS2score=2 15 CHADS2score=1 25 CHADS2score=0 21 LAAV(cm/s) 31±21 LAAA(mm2₎ ₅₀₇_±₂₀₁ LAAFC(%) 26±18 LAAWVbyTEE(cm/s) 8.0±4.7 LAAWVbyTTE(cm/s) 8.3±4.8 LAD(mm) 45±8

HT,hypertension; DM,diabetesmellitus; Warfarin,administration beforethis study;LAAV,leftatrialappendage(LAA)ﬂowvelocityduringatrialcontraction; LAAA,maximalLAAarea;TEE,transesophagealechocardiography;TTE, transtho-racicechocardiography;LAAFC,LAAfractionalchangeduringatrialcontraction; LAAWV,LAAwallmotionvelocityduringLAAcontraction;LAD,leftatrialdimension.

forevaluatingtheriskofischemicstroke/cardiovasculareventsin JapanesepatientswithparoxysmalAForforpredictingclinical out-comesinpatientswithatrialﬁbrillationaftercatheterablationin Asianpatients[17,18].AhighCHADS2score,especiallyincluding strokewithavalue of2,indicatestheneedfor anticoagulation therapyinpatientswithpersistent AF.Thescoremaybeuseful forsecondarypreventionofstrokeinpatientswithpersistentAF. However,thesescoresarenotalwaysconsistentwiththeleftatrial (LA)function.ReducedLAfunctionmayresultinbloodstasisinthe LAandmaycausecardiogeniccerebralembolism.ThereducedLA functionmaycauseSECintheLA.TheseverityofSECisstrongly associatedwithLAAthrombusandembolicevents[19].Therefore, theabilitytopredicttheseverityofSECintheLAwouldbe clin-icallyusefulbecausewecurrentlyanticoagulateallpatientswith severeSEC.Itisveryimportanttononinvasivelyevaluatesevere SECinpatientswithoutastrokehistoryandwithalowCHADS2 score.Inthisstudy,weexaminedthediagnosticroleof transtho-racicLAAWVinrelationtotheCHADS2scoreforevaluatingtherisk ofthrombosisorbloodstasisinpatientswithpersistentAF.

Materialsandmethods

Participants

Thestudypopulationcomprised80consecutivepatientswith persistentnonvalvularAFwhounderwentbothtransthoracicand transesophagealechocardiographyinourlaboratoryfromOctober 2008 to January 2010. Transesophageal echocardiography was orderedbycardiologistsorneurologistsforexaminingtheriskof thromboembolisminthepatientswithAF.Thedatawere retro-spectivelyanalyzed.PersistentAFwasdefinedasAFlastingmore than1weekaccordingtothepastelectrocardiographyorclinical symptoms.Theirmeanagewas69±9years.Patientspredisposed toaorticarchandcarotidsourceswerenotincludedinthestudy. Thecharacteristicsofthe78patientsinwhomLAAWVcouldbe measuredusingtransthoracicTDEareshowninTable1.Among the78patients,61hadaCHADS2score≤2,and17hadaCHADS2 score≥3.Therewere46patientswithaCHADS2score≤1and21 patientswithCHADS2score=0.Twenty-fivepatientshadreceived anticoagulationtherapybeforeparticipationinthisstudy.There were9casesofnewcerebralembolismthatwerediagnosedonthe basisoftheclinicalsignsandfindingsfrommagneticresonance

imaging,computedX-raytomography,andcerebralangiography, oracombinationofthesemethods.Ifstronganticoagulation ther-apyfortheacutephaseofcerebralinfarctionisstartedtooearly, itmaycausebleedingintheinfarctionarea. Therefore,the neu-rologistin our hospitaldid notadminister warfarin during the super-acutephaseofcerebralinfarction.Furthermore,in persis-tent AF,decisions regardinganticoagulation therapy dependon thetransesophagealechocardiographicﬁndings;therefore,asmall numberofpatientsunderwentanticoagulationtherapybeforethis study.

Writteninformedconsentwasobtainedfromallparticipants.

Echocardiographicapparatus

Both transthoracic and transesophageal echocardiographic examinationswereconductedwithanultrasoundsystem(Vivid 7;General ElectricHealthcare, Milwaukee,WI,USA). The mea-surement speciﬁcations for transthoracic TDE were as follows: framerate,141frames/s;frequency,2.6MHz;andsampling vol-umewidth,3.3mm.Asdescribed previously,thecorresponding measurements fortransesophageal TDE wereas follows: frame rate,78frames/s;frequency,3.9MHz;andsamplingvolumewidth, 3.2mm[20].

Transesophagealechocardiography

The peak LAA flow velocity (LAAV) during LAA contraction andthechangeintheLAAfractionalareaduringatrial contrac-tion(LAAFC)wererecordedusingconventionaltransesophageal echocardiographyinthelong-axisview.Weexaminedthe pres-enceofSECintheLAbodyandLAA.Inthepresentstudy,ifSEC wasvisibleonlywhentheechogainwasincreasedby4dBfrom thenormalgainsetting,wedefineditasmildlypositive.IfSECwas visibleatthenormalgainsetting,wedefineditassevere.The nor-malgainsettingwasdefinedasnoexcessivenoiseechointheother cardiaccavity[20].WhentheseverityofSECdifferedbetweenthe LAbodyandLAA,thestrongergradewasrecordedasthe sever-ity.ThepresenceofthrombiandtheseverityofSECwereassessed by3independentinvestigatorsusingtransesophageal echocardio-graphy.Furthermore,theLAAWVatthetipoftheLAAduringLAA contractionwasdeterminedusingpulsedtransesophagealTDE,and themaximumpositivepeakwavevelocitywithineachRRinterval wasaveragedover10cardiaccycles.Atthattime,themitralring motionartifactswerecarefullyneglected.

AnglecorrectionwasnotperformedbecausetheDopplerbeam wasalmostparalleltothemotionofthelongitudinallycontracting appendage(Fig.1).

Transthoracicechocardiography

LAAWVwasmeasuredusing transthoracicTDEwithin1hof thetransesophagealechocardiographyexamination.The triangle-shapedLAAontheleftsideoftheaorticrootintheparasternal short-axisviewwasidentiﬁed.Thesamplevolumewasplacedvery closetothetipoftheLAA,andtheLAAWVwasmeasuredusing pulsedtransthoracicTDE(Fig.1).

LAAWVwascalculatedastheaverageofthemaximumnegative peakwavevelocitywithineachRRintervalover10cardiaccycles excludingthemitralringmotionsignals(Fig.2).TheDopplerbeam anglewascorrectedbyobservingthedirectionofthelongitudinally contractingappendage(Fig.1).TheLAdimensionwas convention-allymeasuredusingM-modetransthoracicechocardiography.

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Fig.1. MeasurementofLAAWVduringtheLAAcontractionphaseusingpulsedtissueDopplerechocardiographywithtransesophageal(leftpanel)andtransthoracic(right panel)echocardiographyinpatientswithatrialﬁbrillation.Thesamplevolume(dottedarrows)forLAAWVmeasurementwasplacedatthetipoftheLAA.Theaverage maximumpositivepeakwavewithineachRRintervalduringLAAcontractionwasdesignatedasLAAWV.AO,aorta;LA,leftatrium;LAA,leftatrialappendage;LAAWV,left atrialappendagewallvelocity;LV,leftventricle;ROI,regionofinterest.

Fig.2.LAAWVduringtheLAAcontractionphasewasmeasuredusingpulsedtissueDopplerechocardiography(leftpanel),andthemitralannularmotionsignals(right panel)weremeasuredusingtransthoracicechocardiographyinpatientswithatrialﬁbrillation.WhentheLAAWV(solidlines)islow,mitralringmotionsignals(dottedlines) aresometimesmistakenforLAAWVreadings.ElectrocardiographicmonitoringisnecessarytodifferentiateLAAWVfrommitralringsignals(dottedlines).AO,aorta;LA,left atrium;LAA,leftatrialappendage;LAAWV,leftatrialappendagewallvelocity;LV,leftventricle;RA,rightatrium;ROI,regionofinterest;RV,rightventricle.

Statisticalanalysis

Simplelinearregressionanalysiswasusedtodetermine cor-relations between different parameters. The differences in the

valuesbetweenthetwogroupswereexaminedusingunpairedt -tests,andthedifferencesinthevaluesamong thethree groups wereexaminedusinganalysisofvariance(ANOVA)witha Bonfer-ronicorrection.TheLAAWVcutoffvaluefordiagnosing cerebral

Table2

CharacteristicsofatrialﬁbrillationpatientswithorwithoutSEC.

Variables SevereSEC MildSEC NoSEC pvalue

Number 48 17 13 – Men 33 13 10 NS Age(years) 69±9 67±9 60±19 NS HT 17 8 2 NS DM 9 3 2 NS Warfarin 21 6 3 NS ThrombusinLAA 13 0 0 0.004* Cerebralembolism 9 0 0 0.028* CHADS2score 2.1±1.4 0.8±0.7 0.5±0.7 <0.001* LAAV(cm/s) 19±13 38±16 60±19 <0.001* LAAA(mm2₎ ₅₃₃_±₂₂₄ ₄₈₉_±₁₆₄ ₄₄₁_±₁₅₀ _NS LAAFC(%) 16±12 36±19 43±12 <0.001* LAAWVbyTEE(cm/s) 5.3±1.8 10.6±3.5 14.1±5.3 <0.001* LAAWVbyTTE(cm/s) 5.7±2.4 10.2±3.3 14.5±5.5 <0.001* LVEF(%) 61±12 66±6 61±14 NS LAD(mm) 48±7 42±8 40±7 <0.001*

SEC,spontaneousechocontrast;NS,notstatisticallysigniﬁcant;p-valuesindicatedifferencesamong3groupsaccordingtoanalysisofvariancewithaBonferroniadjustment; HT,hypertension;DM,diabetesmellitus;Warfarin,administrationbeforethisstudy;LAAV,leftatrialappendage(LAA)ﬂowvelocityduringatrialcontraction;LAAA,maximal LAAarea;TEE,transesophagealechocardiography;TTE,transthoracicechocardiography;LAAFC,LAAfractionalchangeduringatrialcontraction;LAAWV,LAAwallmotion velocityduringLAAcontraction;LAD,leftatrialdimension.

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Fig.3.RegressionanalysisofLAAWVmeasuredbytransesophagealand transtho-racicechocardiographyinpatientswithatrialﬁbrillationwhenanglecorrection wasappliedfortransthoracicechocardiography.LAAWV,leftatrialappendagewall velocity;TEE,transesophagealechocardiography;TTE,transthoracic echocardiog-raphy.

embolismand/or LAAthrombus and for diagnosing severe SEC wasapproximatelyhalf(10cm/s)thenormalvalue(22±3cm/s) mentionedinastudyinvolvinghealthyindividuals[21].The sen-sitivity,speciﬁcity,andpredictivevaluesfordiagnosing cerebral embolism,LAAthrombus,andsevereSECweredeterminedusing LAAWVandCHADS2scores(Table3).Wegroupedthepatientswith embolismand/orLAthrombosistogetherashavingLAthrombus. TheStatisticalPackagefortheSocialSciences(SPSSversion11.0J; SPSSJapanInc., Tokyo,Japan) wasusedforallstatistical analy-sesexceptdiagnosticaccuracy.Statisticalsigniﬁcancewassetat

p<0.05.

Interobserver variability in the LAAWV measurements was calculated asthedifferencebetween twomeasurements ofthe samesubjectperformedbytwodifferentobserversdividedbythe meanvalue.Intraobservervariabilitywascalculatedasthe differ-encebetweentwomeasurementsofthesamesubjectbyasingle observer,dividedbythemeanvalue.

Thestudyprotocolwasapprovedbyourinstitutionalreview board.

Results

ValidationoftransthoracicLAAWVmeasurement

LAAWV was successfully measured using transthoracic TDE in 78 of the 80 patients (98%). The transthoracic LAAWV

patternswerereproducibleandsimilartothoseoftransesophageal LAAWVin theseAFpatients(Fig.1).The LAAWVvalues deter-minedbytransthoracicTDErangedfrom2to26cm/sinpatients withpersistent nonvalvular AF. The LAAWVvalues determined bytransthoracicand transesophagealTDEdidnotdiffer signiﬁ-cantly(9.0±5.9vs.8.7±5.9cm/s,respectively)andwerestrongly correlated (r=0.98)(Fig.3).LAAWVwassigniﬁcantlycorrelated withtransesophagealLAAV(r=0.82,p<0.001)andLAAFC(r=0.56,

p<0.001)(Fig.4).

Theintra-andinterobservervariabilitiesinLAAWV measure-mentbytransthoracicTDEwere5.6%and6.8%,respectively.

LAAWVmeasuredbytransthoracicTDEinrelationtothrombosis

andbloodstasis

Transthoracic LAAWV values were signiﬁcantly lower in patients with cerebral embolism or LAA thrombus than in patients without these conditions (5.0±2.2 vs. 9.3±4.9cm/s,

p<0.001).TransthoracicLAAWVvaluesweresigniﬁcantlylower with increasing SEC severity (severe SEC, mild SEC, with-out SEC: 5.7±2.4, 10.2±3.3, and 14.5±5.5cm/s, respectively) (Table2).

ThrombosisriskevaluationusingtransthoracicLAAWVand

CHADS2score

ACHADS2score≥3had highsensitivityand speciﬁcity(88% and 97%,respectively)for diagnosing cerebralembolism and/or LAA thrombus, but low speciﬁcity (49%) for diagnosing severe SEC.

Inthe78patients,atransthoracicLAAWV<10cm/shada sen-sitivity,specificity,andpositiveandnegativepredictivevaluesof 86%,88%,94%,and77%fordiagnosingsevereSEC.Amongthe61 persistentAFpatientswithaCHADS2score≤2,embolismand/or LAAthrombuswereobservedin2andsevereSECwasnotedin 31.SevereSECwasnotedin13ofthe46persistentAFpatients withaCHADS2score≤1,andin6ofthe21persistentAFpatients withaCHADS2score0.Inthe61patientswithaCHADS2score≤2, atransthoracicLAAWV<10cm/shadasensitivity,specificity,and positiveandnegativepredictivevaluesof81%,92%,94%,and77% fordiagnosingsevereSEC,respectively.Inthe46patientswitha CHADS2score≤1,atransthoracicLAAWV<10cm/shada sensitiv-ity,specificity,andpositiveandnegativepredictivevaluesof74%, 91%,89%,and77%fordiagnosingsevereSEC,respectively(Table3). Inthe21persistentAFpatientswithaCHADS2score0,a transtho-racicLAAWVwas6.8±4.1cm/sin6patientswithsevereSECand

Fig.4.LAAWVplottedagainstLAAﬂowvelocityduringLAAcontraction(LAAV)inpatientswithatrialﬁbrillation(leftpanel).LAAWVplottedagainstLAAfractionalarea duringatrialcontraction(LAAFC)(rightpanel).LAA,leftatrialappendage;LAAWV,leftatrialappendagewallvelocity.

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Table3

AccuracyofdiagnosisofsevereSECpatientsusingtransthoracicLAAWV<10cm/s.

Variables Sensitivity(%) Speciﬁcity(%) Positivepredictive

value(%)

DiagnosingsevereSEC 86 88 94

DiagnosingsevereSECinpatientswithaCHADS2score≤2 81 92 94

DiagnosingsevereSECinpatientswithaCHADS2score≤1 74 91 89

DiagnosingsevereSECinpatientswithaCHADS2score=0 44 83 66

SEC,spontaneousechocontrast;LAAWV,leftatrialappendagewallmotionvelocityduringleftatrialappendagecontraction.

was13.0±6.0cm/sin15patientswithoutsevereSEC(p=0.015). Inthe21persistentAFpatientswithaCHADS2score0,a transtho-racicLAAWV<10cm/shadasensitivity,speciﬁcity,andpositiveand negativepredictivevaluesof44%,83%,66%,and67%fordiagnosing severeSEC.

Discussion

ValidationoftransthoracicLAAWVforassessingLAAfunction PreviousstudiesusingtransthoracicpulsedDoppler echocar-diographysuccessfullymeasuredDopplerflowvelocitiesin62–88% of patients [10,11]. Recently, transthoracic TDE, a noninvasive method,wasdemonstratedtobeusefulforanalyzingLAAfunction in patients with AF [13–15,20]. In the present study, we suc-cessfullydeterminedLAAWVin 98%of thepatientswithAFby usingtransthoracicTDE.Inaddition,thestrongcorrelationbetween transthoracicandtransesophagealLAAWVmeasurementsinthe presentstudymayvalidatetheuseoftransthoracicTDE.Both intra-andinter-observervariabilitiesintransthoracicLAAWV measure-mentswerelow. These findingssuggest that transthoracicTDE ismoreusefulandreliablethanflowvelocitymeasurementwith transthoracicpulsedDopplerechocardiography.Thesuperiorityof TDEoverpulsedDopplerflowmetrymaybeattributedtothe differ-enceintheamplitudeofultrasoundreflectionpowerbetweenthe myocardiumandbloodcellsbecausethemyocardiumisamuch strongerultrasoundreflector.However,caremustbeexercisedto eliminatethemitralannularmotionsignalsconcomitantwiththe TDEsignalofLAAmotion.

LAAWVmeasuredbytransthoracicTDEinrelationtoLA

thrombosisandbloodstasis

SECdeterminedbytransesophagealechocardiographyimplies bloodstasisoraggregationandmaybeanimportantriskfactorfor cerebralembolism[22,23].Uretskyetal.detectedSECinpatients withatransthoracicLAAWV≤13cm/swithasensitivityand speci-ficityof97%and60%,respectively[14].Tamuraetal.showedthat LAAWV<8.7cm/shadasensitivityof77%andaspecificityof76%for diagnosingLAAthrombusformationandwasanindependent pre-dictorofcerebro-vascularevents(hazardratio,3.460)[13,24].We previouslystudiedtheLAAWVduringcontractionandrelaxation inhealthyJapanesesubjectsanditsmeanvalueduring contrac-tionwas22±3cm/s[20].Wetook10cm/sastheLAAWVcutoff forabnormallowvalue,becauseitwasasimpleindexandwas approximatelyhalftheJapanesenormalvalueanditsvalue posi-tionedbetween13cm/stakenbyUretskyetal.and8.7cm/staken byTamuraetal.[13,14].AtransthoracicLAAWV<10cm/salone hadasensitivityandspecificityof86%and88%,respectively,for diagnosingsevereSECinJapanesepatients.Inthepresentstudy, transthoracicLAAWVvaluesweresignificantlylowerwith increas-ingSECseverity.Thus,alowLAAWVvaluemaybeanimportant indicatorofbloodstasisoraggregationintheLAA.

ClinicalvalueoftransthoracicLAAWVinrelationtoCHADS2score

TheCHADS2scoreisawidelyusedclinicalindexfor evaluat-ingtheriskofthromboembolismanddecidingwhethertoinitiate anticoagulanttherapyinpatientswithnonvalvularAF[16].Wealso foundthataCHADS2score≥3hadarelativelyhighsensitivityand specificityfordiagnosingcerebralembolismand/orLAAthrombus. TheseresultssupporttheuseofahighCHADS2scorenotonlyas adiagnosticaidforevaluatingtheriskofthrombosisbutalsoasa clinicalindicatorforstartinganticoagulanttherapyinpatientswith persistentAF.However,sincetheCHADS2scoreincludesstroke withavalueof2,usingittodeterminethesensitivityofpredicting priorstrokeistautological.Virtuallyallclinicianswould antico-agulateapatientwithchronicAFwhohasalreadyhadastroke. ACHADS2scoreof≥3maybeusefulforthesecondary preven-tionofstroke,butitmaynotbeenoughforprimarypreventionof strokeinAFpatients,because,aCHADS2scoremaynotbealways consistentwithLAAfunction.Therefore,wetestedtheclinical sig-nificanceofthetransthoracicLAAWVasanadditionalnoninvasive aidforevaluatingLAAfunctionandthrombogenesis.SevereSECin theleftatriumisawell-knownmarkerofahighriskforthrombosis. ThepredictionofSECseveritywouldbeclinicallyusefulbecausewe currentlyanticoagulateallpatientswithsevereSECregardlessof thepresenceorabsenceofpriorstroke[25–27].Wefoundthata LAAWV<10cm/shadhighsensitivityandspecificityfor diagnos-ingsevereSEC;inaddition,LAAWVwassignificantlylowerwith increasingSECseverity.Itisimportanttononinvasivelyevaluate SECfor primarypreventionofstrokein AFpatientswitha low CHADS2score.Inthepresentstudy,severeSECwasnotedin13 ofthe46persistentAFpatientswithaCHADS2score≤1andin6 patientswithsevereSECeveninthe21patientswithaCHADS2 score0.Inthe46patientswithaCHADS2score≤1,atransthoracic LAAWV<10cm/shadasensitivityandspecificityof74%and91% fordiagnosingsevereSEC.Inthe21persistentAFpatientswith aCHADS2score0,atransthoracicLAAWV<10cm/shada sensi-tivityand specificityof44%and 83%for diagnosingsevereSEC. Thus,atransthoracicLAAWV<10cm/smaybeaspecific diagnos-tictoolforevaluatingsevereSECinthepatientsjudgedashaving alow riskforthrombosisaccordingtotheCHADS2score.From thisperspective,atransthoracicLAAWV<10cm/smaybeasimple andconvenientindicatorforstartinganticoagulationtherapyand maypreventprimarystrokeinthepatientsjudgedaslowriskfor thromboembolismaccordingtotheirCHADS2score.Moreover,we couldsparepatientswithAFwithaCHADS2score_≤2andnormal LAAWVfromanticoagulationtherapytoavoidrelated complica-tions,whileoptimalanticoagulationstrategyforstrokeprevention hasbeennowinvestigatedinJapanesepatientswithAF,J-RHYTHM Registrystudydesign[28].

Limitations

Oneofthemajorlimitationsofthisstudyisitsretrospective designasopposedtoarandomizedprospectiveone.Thenumber ofpatientsenrolledwasrelativelysmall,whichmayhavecauseda selectionbias.

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Itis necessarytocorrecttheangleoftheultrasonicDoppler beamwhenmeasuringtransthoracicLAAWV;theDopplerbeam anglerangedfrom 10◦ to50◦ inthe presentstudy, whichmay have caused some errors. However, in the present study, the LAAWVvalueswerealmostequalbetweentransthoracicand trans-esophagealmeasurements.Wepreviouslyreportedthecorrection of the Doppler beam angle by observing the direction of the longitudinally contracting appendage in normal subjects [20]. Anotherlimitationofthisstudymightbetheultrasonicviewused toobtainthetransthoracicLAAWV;wechosetheparasternal short-axisviewfordeterminingLAAWV.Uretskyetal.andSallachetal. foundnodifferencesintheassessmentofLAAwallmotionbetween theparasternalandapicalviewsintransthoracicechocardiography

[14,15].Inthepresentstudy,thesamplevolumewasplacedasclose aspossibletothetipoftheLAAsinceitisthemostmobilepointin theLAA.However,theregionalLAAwallmotionmayinfacthave differentmyocardialmotionvelocities.Furtherstudiesarerequired toelucidatethesigniﬁcanceofregionalwallmotionintheLAA.

Conclusionsandimplications

Despitesomemethodologicallimitations,transthoracicLAAWV maybeausefulnoninvasivetoolforestimatingLAAfunctionand thrombogenesisespeciallyinpatientswithalow CHADS2score withpersistentAF.

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