pathological cases (MAGYAR-Path) Study speckle tracking echocardiographyin of the heart and great vessels bythree-dimensional syndrome --- Insights from the Motionanalysis Characterization of left atrial dysfunction inhypereosinophilic Cardiologia

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www.revportcardiol.org

Revista Portuguesa de

Cardiologia

Portuguese Journal of Cardiology

ORIGINAL ARTICLE

Characterization of left atrial dysfunction in

hypereosinophilic syndrome --- Insights from the Motion analysis of the heart and great vessels by

three-dimensional speckle tracking echocardiography in pathological cases (MAGYAR-Path) Study

Attila Nemes

^a,^∗

, Imelda Marton

^b

, Péter Domsik

^a

, Anita Kalapos

^a

, Éva Pósfai

^b

, Szabolcs Modok

^b

, Zita Borbényi

^b

, Tamás Forster

^a

a2ndDepartmentofMedicineandCardiologyCenter,MedicalFaculty,AlbertSzent-GyörgyiClinicalCenter,UniversityofSzeged, Szeged,Hungary

bDivisionofHematology,2ndDepartmentofMedicineandCardiologyCenter,MedicalFaculty,AlbertSzent-GyörgyiClinical Center,UniversityofSzeged,Szeged,Hungary

Received9August2015;accepted22November2015

KEYWORDS Echocardiography;

Function;

Leftatrium;

Three-dimensional;

Two-dimensional;

Speckletracking

Abstract

Introduction:Thepresent study was designedto compare three-dimensional speckletrack- ingechocardiography(3DSTE)-derivedleftatrial(LA)volumetric,volume-basedfunctionaland strainparametersbetweenpatientswithhypereosinophilicsyndrome(HES)andmatchedcon- trols.

Methods:A total of 10 HES patients and 19 age- and gender-matched healthy controls wereincludedinthestudy.Completetwo-dimensionalDoppler echocardiographyand3DSTE wereperformedinallHEScasesandcontrols.

Results:Signiﬁcantlyincreasedmaximum(72.9±38.8mlvs.45.6±15.5ml,p=0.01)andminimum (46.3±33.3 ml vs. 26.0±15.0 ml, p=0.03) LA volumes and LA volume before atrial contraction(62.0±36.0mlvs.36.5±16.6ml,p=0.01)werefoundinHESpatientscomparedto controls.Bothpeakglobal(18.3±6.7%vs.25.6±9.0%,p=0.03)andmeansegmental(22.2±6.0%

vs.31.0±12.1%,p=0.04) circumferential strains were signiﬁcantly reducedin HES patients, suggestingdecreasedLAreservoirfunction.

Conclusion:Increased LA volumes can be demonstrated in HES patients, accompanied by reducedLApeakcircumferentialstrainasassessedby3DSTE,suggestingLAremodeling.

∗Correspondingauthor.

E-mailaddress:nemes.attila@med.u-szeged.hu(A.Nemes).

http://dx.doi.org/10.1016/j.repc.2015.11.017

0870-2551/©2174-2049 2016SociedadePortuguesadeCardiologia.PublishedbyElsevierEspaña,S.L.U.Allrightsreserved.

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PALAVRAS-CHAVE Ecocardiograﬁa;

Func¸ão;

Aurículaesquerda;

Tridimensional;

Bidimensional;

Speckle-tracking

Caracterizaçãodadisfunçãoauricularesquerdanasíndromehipereosinofílica--- visãodaanálisedemovimentosdocoraçãoedosgrandesvasosporecocardiografia tridimensionalspeckletrackingemcasospatológicos---estudoMAGYAR-Path

Resumo

Introduc¸ão: Opresenteestudofoiconcebidoparacompararparâmetrosvolumétricosauric- ulares esquerdos derivados porecocardiograﬁa tridimensionalspeckle tracking,parâmetros funcionaisestrainbaseadosnovolumeentredoentescomsíndromehipereosinofílicaecontro- losequiparados.

Métodos: UmtotaldedezdoentesHESede19controlossaudáveis,equiparadosparaidadee género,foramincluídosnoestudo.Oestudocompletoecocardiográﬁcobidimensional,Doppler e3DSTE,foirealizadoemtodososcasosHESecontrolos.

Resultados:Encontrou-se em doentes com HES, comparativamente com os controlos, um aumentosignificativodosvolumesauricularesesquerdos(72,9±38,8mlversus45,6±15,5ml, p=0,01),mínimo(46,3±33,3mlversus26,0±15,0ml,p=0,03)evolumeauricularesquerdo antesdacontraçãoauricular(62,0±36,0mlversus36,5±16,6ml,p=0,01).Ambosstrains circunferenciaispico,global(18,3 ±6,7%versus25,6±9,0%, p=0,03) esegmentar médio (22,2±6,0%versus31,0±12,1%,p=0,04)eramsignificativamentereduzidosemdoentesHES, sugerindodiminuiçãodefunçãoauricularesquerdadereservatório.

Conclusão:Oaumentodevolumes auricularesesquerdos foidemonstradonos doentesHES, sendoacompanhadoporreduc¸ãodestraincircunferencialpicodaaurículaesquerdaconforme avaliadopor3DSTE,sugerindoremodelagemauricularesquerda.

Introduction

Hypereosinophilicsyndrome(HES) ischaracterizedbyper- sistently elevated eosinophil count (>1500 cells/ml) in peripheralbloodforatleastsixmonths,andsingle-ormul- tipleend-organdamageattributabletocytotoxicinjuryby eosinophils.¹Intheliteraturetheoverallprevalenceofcar- diovascular involvementis40---50% ofHES patients.^1---3 The early stageofcardiacinvolvementconsistsof eosinophilic infiltration,followedbyanintermediatethromboticstage, and finally a late fibrotic stage. An enlarged atrium with normal-sizedleftventricleisaminorcriterionforendomy- ocardialfibrosis.¹Atpresentlittleisknownaboutleftatrial (LA)functioninHES.Three-dimensional(3D)speckletrack- ingechocardiography(3DSTE)isanewnon-invasiveclinical toolfor volumetricandstrainanalysisoftheleftatrium.⁴ Thepresentstudywasdesignedtocompare3DSTE-derived LAvolumetric,volume-basedfunctionalandstrainparame- tersbetweenHESpatientsandmatchedcontrols.

Methods

Subjects

Atotalof10HESpatientswereincludedinthepresentstudy.

ThediagnosisofHESwasconﬁrmedinallpatientsaccording totheavailableguidelines.⁵OneHESpatienthadahistoryof non-ST-elevationmyocardial infarction;theothersshowed no signiﬁcant cardiac alterations and were asymptomatic at thetime of examination. Theirresults werecompared

to19age-andgender-matchedhealthycontrols.Complete two-dimensional(2D)Dopplerechocardiographyand3DSTE wereperformedinallHESpatientsandcontrols.Thepresent workisapartoftheMotionAnalysisoftheheartandGreat vesselsbYthree-dimensionAlspeckle-tRackingechocardiog- raphyinPathologicalcases(MAGYAR-Path)Study(‘Magyar’

means‘Hungarian’intheHungarianlanguage),carriedout atthe2ndDepartmentofMedicineandCardiologyCenter, Szeged,Hungarytovalidate3DSTE-derivedparameters,to examinetheirdiagnosticandprognosticsigniﬁcanceandto compare them toother known(patho)physiological varia- blesinpathologicalcases.Theprotocolwasapprovedbythe institutionalreviewboard,conformingtotheethicalguide- linesofthe1975DeclarationofHelsinki,andeachsubject providedwritteninformedconsent.

Two-dimensionalDopplerandtissueDoppler echocardiography

Transthoracicimagingwasperformedbyexperiencedinves- tigatorsusinga1---5MHzPST-30SBPphased-arraytransducer in a Toshiba Artida^TM cardiac ultrasound system (Toshiba MedicalSystems,Tokyo,Japan).Completetwo-dimensional echocardiographywasundertakenwiththepatientin left lateraldecubitus position,usingbothapicaland paraster- nal views in all cases. Ejection fractionwas measured in parasternallong-axisviewbytheTeichholzmethod.⁶Color Doppler echocardiography was used to visually quantify degree of mitral regurgitation(MR). TissueDoppler echo- cardiographywasusedtocalculatetheE/Eratiofollowing pulsedDoppler-derivedmitralinﬂowE/Ameasurements.

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Three-dimensionalspeckletracking echocardiography

3DSTEdatasetswereacquiredfromanapicalwindowusing a1-4MHzmatrixphased-arraytransducer(PST-25SX).⁴Fol- lowingoptimizationofgainsetting,full volumemode was used over six consecutive cardiac cycles during a single breath-hold.Thevolumedatawerestoredinrawdatafor- matforfurtheranalysis.LAquantificationswereperformed using3DWallMotionTrackingsoftware,version2.7(Toshiba MedicalSystems,Tokyo,Japan). Each 3Ddataset wasdis- played in multiple planes, including apical two- (AP2CH) andfour-chamber(AP4CH)views,andthreeshort-axisviews at differentLA levelsfromthe base tothe apex.Several referencepoints onthe LA endocardium were set by the examinerinAP2CHandAP4CHviews.Thefirstpointswere setat theedgeof theseptalmitralvalveannulus (atthe origin of the anterior mitral leaflet), then markers were placedin counterclockwise rotationaround the LAtothe lateralmitralvalveannulus(to theoriginof theposterior leaflet)inAP4CHview.DuringthestudiestheLAappendage andthepulmonaryveinswereexcludedfromtheLAcavity.

MeasurementswereperformedﬁrstinAP4CHview,thenin AP2CHview.AfterdetectionoftheLAmyocardialbordersat theend-diastolic referenceframe, theuser could correct

theLAshape,ifnecessary.3Dwallmotiontrackingwasthen automaticallyperformedthroughtheentirecardiaccycle.

Three-dimensionalspeckletracking echocardiographyforleftatrialvolumetric measurements

From time curves of global LA volume changes, maxi- mum(Vmax)andminimum(Vmin)LAvolumesandLAvolume beforeatrialcontraction(VpreA)weremeasuredfromthe3D echocardiographicdatasetsjustbeforemitralvalveopening (end-systole),justbeforemitralvalveclosure(end-diastole) andattimeofPwaveonECG(earlydiastole),respectively (Figure1).^7---10 LAfunctionconsistsofthreephases:thesys- tolic reservoir phase, and the diastolic passive (conduit) andactiveemptying(boosterpump) phases.Tocharacter- izethesefunctions,strokevolumesandemptyingfractions werecalculatedfromtheabove-mentionedvolumes:

LAstrokevolumes:

- Total atrial stroke volume (TASV): Vmax−Vmin (reservoir function)

- Passiveatrial stroke volume(PASV): Vmax−VpreA (conduit function)

LV LV

LA LA

RV

RA

V_max V_preA V_min

C3 A B

C5

C7 30.00

–30.00 [%]

[%]

45.0 51 251.251.251.251 251.251 251 251 251 251 251 251 251 251 25151 25151 251 251 251 255151551.25555151515151 251.25151 25151 2551 25151.21 21 211 21 21.21 21 21 21 21 2111 2111111 21 21 222222222222222222222222222222222222222222222222222222

–11.49 55.0 Time: 0 msec

#1512 [mL]

[msec]

0.0 30.0

15.0 0.0 –15.0 Long. Strain

Long. Strain

27.0 vps G:66 DR:60 3SX1 T3.5

EDV 51.02 mL 371 msec 0 msec est. MASS 28.44 mL

44.26 % 21.84 g ESV EF 1.05*MV

Figure1 Imagesfromthree-dimensionalfull-volumedatasetshowingleftatrium:apical4-chamber(A)and2-chamberviews(B) andshort-axisviewsatbasal(C3),mid-(C5)andsuperior(C7)leftatriallevelaredemonstratedtogetherwithleftatrialvolumetric dataandathree-dimensionalcastoftheleftatrium.Time-segmentalstraincurvesofall16leftatrialsegmentsandgloballeft atrialvolumechangesthroughoutthecardiaccyclearealsopresented.Whitearrow:peakstrain.LA:leftatrium;LV:leftventricle;

RA:rightatrium;RV:rightventricle;Vmax,VminandVpreA:maximumandminimumleftatrialvolumesandleftatrialvolumebefore atrialcontraction,respectively.

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Table1 Clinicaldataofpatientswithhypereosinophilicsyndrome.

Case Yearof birth

Yearof diagnosis

Organinvolvement Hepatomegaly/

splenomegaly

Cardiacdisease

1 1961 2013 Duodenaleosinophilia Splenomegaly -

2 1938 2009 - - -

3 1966 2010 - - -

4 1945 2011 Tissueeosinophilia - -

5 1936 2013 - - NSTEMI(2013)

6 1940 2009 Eosinophilicdermatitis - -

7 1966 2011 Sensory-motorneuropathy,pulmonary

involvement,suralnerve

granulomatousnecrotizingvasculitis

Splenomegaly -

8 1954 2013 - - -

9 1961 2002 - - -

10 1941 2014 Asthma,vasculitis - -

NSTEMI:non-ST-elevationmyocardialinfarction.

- Active atrial stroke volume (AASV): VpreA−Vmin (booster pump/activecontractionfunction).

LAemptyingfractions:

- Total atrial emptying fraction (TAEF): TASV/Vmax×100 (reservoirfunction)

- Passive atrial emptying fraction (PAEF): PASV/Vmax×100 (conduitfunction)

- Active atrial emptying fraction (AAEF): AASV/VpreA×100 (boosterpump/activecontractionfunction).

Three-dimensionalspeckletracking echocardiographyforleftatrialstrain measurements

Fromthesame3Dechocardiographicdatasets,timecurves ofone-directionalradial(RS),longitudinal(LS)andcircum- ferential(CS)strainswerealsogeneratedforeachsegment usingthe16-segmentmodelobtainedfortheleftventricle (Figure1).^10---12Moreover,duetotheabilityof3DSTEtocal- culatecomplexstrains,areastrain(ratioofendocardialarea changeduringthecardiaccycle)and3Dstrain(straininthe wall thickening direction, combination of one-directional strains)werealsomeasured.Oneachtime-segmentalstrain curve,peakstrainsrepresentingcharacteristicsofthereser- voir phase of LA function were measured. Global strains werecalculatedbythesoftwareconsideringthewholeLA, while mean segmentalstrainswereobtained asthemean of strains of 16 segments. The softwarecalculated these parametersautomatically.

Statisticalanalysis

Continuous variables are expressed as mean ± standard deviation.Allstatisticaltestsweretwo-sidedandapvalue

<0.05 wasregarded asstatistically signiﬁcant. Continuous variables were assessed by the unpaired Student’s t test, whilecategoricalvariableswereassessedbythechi-square test andFisher’sexacttest. Correlationswereestablished by calculation of Pearson correlation coefﬁcients. The

statistical analysis wasperformed with MedCalc software (MedCalc,Inc.,Mariakerke,Belgium).

Results

The clinical data of each patientincluding organinvolve- mentarepresentedinTable1.Onlyonepatienthadahistory ofcardiacdisease(non-ST-elevationmyocardialinfarction).

The laboratory ﬁndings were as follows (HES vs. controls): red blood cell count: 4.2±0.5 T/l vs. 4.3±0.4 T/l (p=0.94); hemoglobin: 126.7±18.8 g/l vs. 130.1±10.2 g/l (p=0.86); platelet count: 276.3±176.7×10⁹/l vs.

282.4±158.2×10⁹/l;hematocrit:36.9±5.5%vs.37.8±4.9%;

whitebloodcellcount:16.7±5.8×10⁹/lvs.6.8±1.2×10⁹/l (p=0.02); eosinophil ratio: 49.0±16.6% vs. 3.2±2.3%

(p=0.001);andabsoluteeosinophilcount:8.7±4.8×10⁹/lvs.

0.4±0.1×10⁹/l(p=0.001).Nocorrelationscouldbedemon- strated between any of the laboratory ﬁndings and 2D echocardiographic and 3DSTEdata in this patientpopula- tion.

Theroutinetwo-dimensionalechocardiographicdataare presentedinTable2.NoneofthecontrolsorHES patients showedgrade>1mitralortricuspidregurgitation.OnlyLA diameterandinterventricularseptalthicknessshowedsig- niﬁcantdifferencesbetweenHESpatientsandcontrols.

The 3DSTEdata arepresented in Table 3. Signiﬁcantly increasedmaximum(p=0.01)andminimum(p=0.03)LAvol- umesandLAvolumebeforeatrialcontraction(p=0.01)and elevated total (p=0.02) and active (p=0.005)atrial stroke volumescharacterizingLAreservoirandboosterpumpfunc- tions werefound in HESpatients ascomparedtocontrols (Table 3). All emptying fractions did not differ between groups.BothglobalandmeansegmentalpeakCSweresig- niﬁcantlyreducedinHESpatients,suggestingdecreasedLA reservoirfunction(Table4).

Discussion

Cardiacmanifestationsarethemajorcauseofmorbidityin HES and follow three stages. The ﬁrst,an acute necrotic stage,isduetoinﬁltrationofeosinophilsinthemyocardium

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Table2 Clinical and two-dimensional echocardiographic characteristics of patients with hypereosinophilic syndrome and controls.

HESpatients(n=10) Controls(n=19) p

Riskfactors

Age(years) 58.1±13.1 51.2±12.6 0.18

Malegender(%) 7(70) 11(58) 0.69

Bodysurfacearea(m²) 1.78±0.13 1.77±0.12 0.92

Bodymassindex(kg/m²) 26.7±1.1 25.3±1.0 0.09

Two-dimensionalechocardiography

LAdiameter(mm) 39.5±3.5 32.9±2.2 0.0005

LVEDD(mm) 53.0±11.6 47.4±4.6 0.07

LVEDV(ml) 120.0±46.8 104.5±22.4 0.24

LVEDV/BSA(ml/m²) 67.2±25.3 59.4±14.3 0.42

LVEDV/BMI(ml/[kg/m²]) 4.5±1.9 4.1±0.9 0.58

LVend-systolicdiameter(mm) 36.1±12.5 31.1±4.6 0.13

LVend-systolicvolume(ml) 47.8±25.0 37.7±11.0 0.14

LVESV/BSA(ml/m²) 26.9±13.9 21.6±7.5 0.32

LVESV/BMI(ml/[kg/m²]) 1.8±0.9 1.5±0.5 0.39

Interventricularseptum(mm) 11.0±0.7 8.7±1.7 0.0003

LVposteriorwall(mm) 9.5±1.2 9.7±2.5 0.81

LVejectionfraction(%) 60.5±12.4 63.9±6.5 0.33

E/Aratio 1.88±0.16 1.43±0.28 0.05

E/Eratio 10.2±3.4 6.53±1.15 0.04

BMI:bodymassindex;BSA:bodysurfacearea;HES:hypereosinophilicsyndrome;LA:leftatrial;LV:leftventricular;LVEDD:leftventricular end-diastolicdiameter;LVEDV:leftventricularend-diastolicvolume;LVESD:leftventricularend-systolicdiameter;LVESV:end-systolic volume.

Table3 Comparisonofthree-dimensionalspeckletrackingechocardiography-derivedvolumetricandvolume-basedleftatrial functionalparametersofpatientswithhypereosinophilicsyndromeandcontrols.

Calculatedvolumes

Vmax(ml) 72.9±38.8 45.6±15.5 0.01

Vmax/BSA(ml/m²) 41.8±25.0 26.0±9.7 0.03

Vmax/BMI(ml/[kg/m²]) 2.8±1.5 1.8±0.6 0.03

Vmin(ml) 46.3±33.3 26.0±15.0 0.03

Vmin/BSA(ml/m²) 26.8±21.4 14.9±9.7 0.05

Vmin/BMI(ml/[kg/m²]) 1.7±1.2 1.0±0.6 0.05

VpreA(ml) 62.0±36.0 36.5±16.6 0.01

VpreA/BSA(ml/m²) 35.7±23.1 20.9±10.4 0.03

VpreA/BMI(ml/[kg/m²]) 2.3±1.4 1.4±0.7 0.03

Strokevolumes

TASV(ml) 26.6±8.5 19.6±6.4 0.02

TASV/BSA(ml/m²) 15.0±4.9 11.1±3.6 0.04

TASV/BMI(ml/[kg/m²]) 1.0±0.3 0.8±0.3 0.12

PASV(ml) 10.9±8.2 9.1±5.0 0.47

PASV/BSA(ml/m²) 6.1±4.6 5.1±2.8 0.61

PASV/BMI(ml/[kg/m²]) 0.4±0.3 0.4±0.2 0.78

AASV(ml) 15.7±5.1 10.5±4.0 0.005

AASV/BSA(ml/m²) 8.9±2.9 5.9±2.3 0.01

AASV/BMI(ml/[kg/m²]) 0.6±0.2 0.4±0.2 0.03

Emptyingfractions

TotalatrialEF(%) 40.0±10.5 45.0±12.9 0.29

PassiveatrialEF(%) 15.9±11.7 21.4±10.8 0.21

ActiveatrialEF(%) 28.6±7.8 30.5±9.5 0.58

AASV:activeatrialstrokevolume;BMI:bodymassindex;BSA:bodysurfacearea;EF:emptyingfraction;HES:hypereosinophilicsyndrome;

LA:leftatrial;PASV:passiveatrialstrokevolume;TASV:totalatrialstrokevolume;Vmax:maximumleftatrialvolume;V_min:minimum leftatrialvolume;V_preA:leftatrialvolumebeforeatrialcontraction.

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Table4 Comparisonofthree-dimensionalspeckletrackingechocardiography-derivedpeakglobalandmeansegmentalstrain parametersofpatientswithhypereosinophilicsyndromeandcontrols.

Globalstrainparameters

Radialstrain(%) ---17.7±7.7 ---15.7±11.6 0.64

Circumferentialstrain(%) 18.3±6.7 25.6±9.0 0.03

Longitudinalstrain(%) 21.0±6.2 22.3±8.7 0.68

3Dstrain(%) ---10.1±5.0 ---9.3±9.0 0.81

Areastrain(%) 41.2±13.8 50.7±20.4 0.20

Meansegmentalstrainparameters

Radialstrain(%) ---20.6±6.1 ---19.5±8.1 0.70

Circumferentialstrain(%) 22.2±6.0 31.0±12.1 0.04

Longitudinalstrain(%) 21.8±6.4 25.6±7.5 0.18

3Dstrain(%) ---14.7±4.3 ---13.7±6.7 0.67

Areastrain(%) 45.6±13.1 58.3±21.7 0.10

3D:three-dimensional;HES:hypereosinophilicsyndrome.

andismostlyasymptomatic.¹³Theinitialdamageisthought to be caused by eosinophilic granules. The intermediate (thrombotic)phaseischaracterizedbythrombusformation followedbyorganizationofthethrombusintoathicklayer of granulation tissue. In the third, fibrotic stage, granulation tissue changes intofibrosis, sometimes stillwith a small inflammatory zone.¹³ Nowadays the term ‘Löffler’s endomyocarditis’ is used to describe the involvement of the heart in HES in the thrombotic and fibrotic stage.¹⁴ Typical echocardiographic findings in HES areendocardial thickening, fibrothromboticobliteration of theventricular apices,andvalvularregurgitationduetorestrictedmotion of the posterior mitral leaflet as assessed by 2D Doppler echocardiography.^1---3,13

In the present study,most HES patients had noknown cardiac disease or clinical signs of thrombosis or fibrosis at enrollment (except case 5). They were presumably in thefirst,asymptomatic stage,therefore thealterationsin LA morphology and function would be related solely to HES.OnlyleftventricularhypertrophyanddilatedLAcould bedetectedbyconventional2DDopplerechocardiography, without significant valvular regurgitationor thrombusfor- mation. 3DSTEconfirmedLAvolumechangesin allphases of LA function and found alterations in both peak global and mean segmental LACS, suggesting reduced reservoir functionandLAremodeling.

Awidevarietyofpathophysiologicalchangesmayleadto LAremodeling,withstructural,functional,neurohormonal or other consequences.¹⁵ The real mechanism behind LA remodelinginHESisnotknown,butmyocytenecrosisand alterations in the extracellular matrix and in the release of atrial hormones duetotoxic proteinsfromdegranulat- ingeosinophilsanddiastolicdysfunctioncouldtheoretically explainourﬁndings.¹⁵

3DSTE is a new clinical tool for non-invasive 3D cardiac chamber quantiﬁcations of the left ventricle and atrium based on a block-matching algorithm of myocar- dial speckles during their frame-to-frame motion.⁴ 3DSTE has been demonstratedtobe useful for LAvolumetric^7---10 andstrain^10---12 assessments,allowingmoredetailedassess- ment of LA functionfrom thesame 3D dataset. Different

patterns in 3DSTE-derived volume-based and strain functional properties can be demonstrated in different disorders.In a recent3DSTE study,peakLA RS andLALS werefoundtobealteredinhypertrophiccardiomyopathy, togetherwithpreserved LACS.¹⁰ In anotherstudy,strains at all LAlevelsshowed alterations in atrial ﬁbrillation by 3DSTE.¹²Inthepresentstudy,onlypeakLACSwasdecreased inHESpatients,whileRSandLSremainedunchanged.The realpathologicalmechanismbehindthereasonthatonlyLA CSshowsalterationsinHESisnotknown,buthemodynamic reasons and their relationship with LA ﬁber orientation cannot be excluded, beyondthe above-mentioned patho- physiologicfactors.

Limitations

Severalimportantlimitationsoftheassessmentsshouldbe takenintoaccount,includinglowerimage qualityascom- pared to 2D echocardiography. Only a limited number of HES patients were examined,which should beconsidered wheninterpretingtheresults.However,HES isarelatively raredisease. Coronary angiographywasperformed in one HEScase,withanegativeresult.Moreover,transesophageal echocardiographywasnotperformedtoexcludethrombiin HESpatients.

Conclusions

Increased LA volumes and stroke volumes were demon- stratedin HES patients,accompanied byreducedLApeak circumferential strainasassessedby3DSTE.These results suggest structural and functional LA remodeling in HES patients.

Ethical disclosures

Protection of human and animal subjects.The authors declare that theprocedures followed werein accordance withtheregulationsoftherelevantclinicalresearchethics

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committeeandwiththoseoftheCodeofEthicsoftheWorld MedicalAssociation(DeclarationofHelsinki).

Conﬁdentialityofdata.Theauthorsdeclarethattheyhave followedtheprotocolsoftheirworkcenteronthepublica- tionofpatientdata.

Right to privacy and informed consent.The authors declarethatnopatientdataappearinthisarticle.

Conﬂicts of interest

Theauthorshavenoconﬂictsofinteresttodeclare.

Acknowledgments

TheauthorsexpresstheirthankstoDrsLászlóKrenácsand Enik˝oBagdifortheiropiniononthepathologicalaspectsof thecases,andtoHajnalkaAndrikovicsformoleculartests.

References

1.KleinfeldtT,NienaberCA,KischeS,etal.Cardiacmanifesta- tionofthehypereosinophilicsyndrome:newinsights.ClinRes Cardiol.2010;99:419---27.

2.Sen T, Gungor O, Akpinar I, et al. Cardiac involvement in hypereosinophilic syndrome. Tex Heart Inst J. 2009;36:

628---9.

3.ShahR,AnanthasubramaniamK.Evaluationofcardiacinvolve- mentinhypereosinophilicsyndrome:complementaryrolesof transthoracic,transesophageal,andcontrastechocardiography.

Echocardiography.2006;23:689---91.

4.NemesA,KalaposA,DomsikP,etal.Three-dimensionalspeckletracking echocardiography --- a further step in non-invasive three-dimensional cardiac imaging. Orv Hetil. 2012;153:

1570---7.

5.ChusidMJ,DaleDC,WestBC,etal.Thehypereosinophilicsyn- drome:analysisoffourteencaseswithreviewoftheliterature.

Medicine(Baltimore).1975;54:1---27.

6.TeichholzLE,CohenMV,SonnenblickEH,et al.Studyofleft ventricular geometry and function by B-scan ultrasonogra- phy in patients with and without asynergy. N Engl J Med.

1974;291:1220---6.

7.Kleijn SA, Aly MF, Terwee CB, et al. Comparison between direct volumetric and speckle tracking methodologies for left ventricular and left atrial chamber quantiﬁcation by three-dimensional echocardiography. Am J Cardiol.

2011;108:1038---44.

8.NagayaM,KawasakiM,TanakaR,etal.Quantitativevalidation ofleft atrialstructure and function bytwo-dimensional and three-dimensionalspeckletrackingechocardiography:acom- parativestudywiththree-dimensionalcomputedtomography.

JCardiol.2013;62:188---94.

9.Nemes A, Domsik P, Kalapos A, et al. Comparison of three-dimensionalspeckletrackingechocardiographyandtwo- dimensionalechocardiographyforevaluationofleftatrialsize andfunctioninhealthyvolunteers(resultsfromtheMAGYAR- HealthyStudy).Echocardiography.2014;31:865---71.

10.Domsik P, Kalapos A, Chadaide S, et al. Three-dimensional speckle tracking echocardiography allows detailed evalua- tion of left atrial function in hypertrophic cardiomyopathy --- insights from the MAGYAR-Path Study. Echocardiography.

2014;31:1245---52.

11.MochizukiA,YudaS,OiY,etal.Assessmentofleftatrialdefor- mation and synchrony by three-dimensional speckle-tracking echocardiography: comparative studies in healthy subjects and patients withatrial ﬁbrillation. J Am Soc Echocardiogr.

2013;26:165---74.

12.Chadaide S, Domsik P, Kalapos A, et al. Three-dimensional speckle tracking echocardiography-derived left atrial strain parameters are reduced in patients with atrial ﬁbrillation (results from the MAGYAR-Path study). Echocardiography.

2013;30:1078---83.

13.TenOeverJ,TheunissenLJ,TickLW,etal.Cardiacinvolvement inhypereosinophilicsyndrome.NethJMed.2011;69:240---4.

14.Crossmitt EP, Trip MD, Durrer JD. Löfﬂer’s endomyocardi- tisin theidiopathic hypereosinophilic syndrome.Cardiology.

1999;91:272---6.

15.Casaclang-Verzosa G, Gersh BJ, Tsang TS. Structural and functionalremodeling ofthe leftatrium: clinicaland thera- peuticimplications for atrial ﬁbrillation. J Am CollCardiol.

2008;51:1---11.