MAGYAR-Path Study case from the three-dimensional speckle-trackingechocardiographic lymphoma patient with cardiac involvement:A Left ventricular rigid body rotation in a diffuse largeB-cell Cardiologia

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www.revportcardiol.org

Revista Portuguesa de

Cardiologia

Portuguese Journal of Cardiology

CASE REPORT

Left ventricular rigid body rotation in a diffuse large B-cell lymphoma patient with cardiac involvement:

A case from the three-dimensional speckle-tracking echocardiographic MAGYAR-Path Study

Dóra Földeák

^a

, Anita Kalapos

^b

, Péter Domsik

^b

, Mária Sinkó

^c

, Nóra Szeleczki

^c

, Enik˝ o Bagdi

^d

, László Krenács

^d

, Tamás Forster

^b

, Zita Borbényi

^a

, Attila Nemes

^b,^∗

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

b2ndDepartmentofMedicineandCardiologyCenter,MedicalFaculty,AlbertSzent-GyörgyiClinicalCenter,UniversityofSzeged, Szeged,Hungary

cPET/CTCentre,Bács-KiskunCountyHospital,Kecskemét,Hungary

dLaboratoryofTumorPathologyandMolecularDiagnostics,Szeged,Hungary

Received5January2016;accepted26April2016 Availableonline1February2017

KEYWORDS Three-dimensional;

Speckle-tracking;

Echocardiography;

Lymphoma;

Rotation;

Twist

Abstract SecondarymyocardialinvolvementbydiffuselargeB-celllymphomaisarareoccur- rence.Left ventricular (LV) twist is consideredan essential partof LV function. In normal circumstances LV twist results from the movement of two orthogonally oriented muscular bandsofahelicalmyocardialstructurewithconsequent clockwiserotationofthebaseand counterclockwiserotation of the apex.Three-dimensional (3D) speckle-tracking echocardiography(3DSTE)hasbeenfoundtobefeasiblefor non-invasive3DquantiﬁcationofLVwall motionandrotationalmechanics. Thepresentreportaimedto assessLVtwisting motionin apatient with diffuse largeB-celllymphoma withpositron emission tomography/computer tomography-provencardiacinvolvementby3DSTE.During3DSTE,reductioninsomesegmental radial,longitudinal,circumferential,areaand3D LVstrainswerefound.ApicalandbasalLV rotationswerefoundtobeinthesamecounterclockwisedirection,conﬁrmingnearabsenceof LVtwist---so-calledrigidbodyrotation.

∗Correspondingauthor.

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

http://dx.doi.org/10.1016/j.repc.2016.04.015

2174-2049

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PALAVRAS-CHAVE Tridimensional;

Speckle-tracking;

Ecocardiograﬁa;

Linfoma;

Rotac¸ão;

Torc¸ão

«Rotac¸ãocorporalrígida»ventricularesquerdanumdoentecomlinfomadifusode célulasBeenvolvimentocardíaco.Umcasodeecocardiograﬁatridimensional despeckle-tracking---estudoMAGYAR-Path

Resumo Oenvolvimentodomiocárdiosecundárioao linfomadifusodecélulasgrandesBé umaocorrênciarara.Atorçãoventricularesquerda(VE)éconsideradaumaparteessencialda funçãoVE.Emcircunstânciasnormais,atorçãodoVEresultadomovimentodeumaestrutura miocárdicahelicoidal de duasbandasmusculares orientadasortogonalmente, comaconse- quenterotaçãonosentidodosponteirosdorelógiodabasedoVEerotaçãocontraosponteiros dorelógiodoápexdoVE.Aecocardiografiatridimensional(3D)despeckle-tracking(3DSTE)foi consideradaadequadaparaaquantificação3DnãoinvasivadacontratilidadesegmentarVEe damecânicaderotação.Esteartigotemcomoobjetivoaavaliaçãodomovimentodetorção VEpor3DSTEnumdoentecomlinfomadifusodecélulasgrandesBeenvolvimentocardíaco comprovadoportomografiadeemissãodepositrões/tomografia.Por3DSTEfoiverificadauma certareduçãodostrainradial,longitudinal,circunferencialdoVE.A rotaçãodossegmentos basaiseapicaisdoVEfoisemelhante,nummesmosentido,contraosponteirosdorelógio.Tal conduziuaumareduçãomarcadadatorçãodoVE---rigidbodyrotations.Detetaram-serotações VEapicaisebasaisnosentidocontrárioaodosponteirosdorelógio,confirmandoaausência próximadatorçãoVEconformereferido«rotaçãorígidadocorpo».

Introduction

Secondary myocardial involvement by diffuse large B-cell lymphomais an uncommon occurrence. Primarymediasti- nal B-cell lymphoma is an uncommon aggressive subset of diffuse large B-cell lymphoma.¹ It frequently spreads locallyfromthethymusintothepleuraandthepericardium, butrarelyinvadesdirectlythroughtheheart.¹Itoccasion- allymanifestsasan intracardiacmass,oftendiagnosedon autopsy,and 90%areclinically silent.^2,3 This typeof lym- phomaismoreprevalentinwomen,mainlyinthethirdand fourthdecadesoflife,andrepresents2-3%ofnon-Hodgkin’s lymphomas.^1,4 It usuallypresentswithsystemic symptoms (weightloss,fever,nightsweats),shortnessofbreath,chest discomfort,andpalpablelymphnodes.

Leftventricular(LV)twistisconsideredanessentialpart ofLVfunction.⁵InnormalcircumstancesLVtwistresultsfrom themovementoftwoorthogonallyorientedmuscularbands ofahelicalmyocardialstructurewithconsequentclockwise rotationoftheLVbaseandcounterclockwiserotationofthe LV apex.⁶ This twisting deformation plays a fundamental partinthemechanicalefficiencyoftheheart,resultingin 60%ejectionfraction(EF) withonly15%fibershortening.⁷ Recent developments in speckle-tracking echocardiography (STE) provide an opportunity to make accurate, reproducibleand bedside assessmentsof LV twist in daily clinicalpractice.⁵Three-dimensional(3D)speckle-tracking echocardiography (3DSTE) has been found to be feasible for non-invasive 3D quantification of LV wall motion and rotationalmechanics.⁸The presentreportaimedtoassess LVtwistingmotioninapatientwithdiffuselargeB-celllym- phomawithpositronemissiontomography(PET)/computer tomography (CT)-proven cardiac involvement by 3DSTE.

Case report

A52-year-oldfemalepatientwasadmittedtothehospital due toshortnessof breath.As apart of herexamination, chest andabdominalCTwasperformed, onwhichseveral pathological lymphnodes couldbe observed in themedi- astinal and abdominal regions together with pleural and pericardialeffusions.Intheupperthirdofthemediastinum, a softtissuemasswasdetected,fromwhichabiopsy was taken. Histology conﬁrmeda CD20-positive primarymedi- astinal lymphoma,which isconsidered asubset of diffuse large B-cell lymphoma and is an uncommon clinical and pathological entityin theWorld HealthOrganization clas- siﬁcationoflymphomas.^1,4

Chemotherapywithrituximab,cyclophosphamide,doxo- rubicin, vincristine and methylprednisolone (R-CHOP) was started according to international recommendations.⁹ R-CHOPincludesrituximab,ananti-CD20antibody,anessen- tial part of the treatment. Following four cycles every 21days,chestCTwasrepeated,whichdetectedsmalllymph nodesinthehilarregionsandintherightparatrachealarea.

Thus,according totheCTscan, thetreatmentresulted in partialresponse.

Altogether, the patient received eight cycles of such chemotherapy. After completion of the treatment, a combined low-dose plain CT and ¹⁸F-ﬂuorodeoxyglucose (FDG)-PETexaminationwasperformedusingaSiemensBio- graph 6 PET/CT scanner (Siemens Healthcare, Erlangen, Germany).PET/CTshowedactivityinthemediastinalregion andasingle2cm×5cmactivelymphnodeinthelefthilar region.Regardingdiseaseactivity,thepatientreceived39.6 Gyofradiationtothemediastinalarea.Threeweekslater, palpablemassescouldbedetectedduringphysical examination inthe leftandright lowerlimb region.Biopsy was

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Figure1 Positronemissiontomography/computedtomographyimageofthepatientwithdiffuselargeB-celllymphomashowing dorsalfocal¹⁸F-ﬂuorodeoxyglucoseaccumulationinthemyocardium(whitearrows).

performed oftheleft-sidemass,showingextranodalman- ifestation of the disease. The patient went through two cyclesofsalvagechemotherapy(rituximab,cisplatin,cyto- sinearabinosideanddexamethasone,R-DHAP)andstemcell collection was also performed. Following treatment, the skinmanifestationsdisappeared.

Autologousstemcelltransplantationwasplannedasthe nexttreatmentoptionintheeventofcompleteremission.

To conﬁrm theresponse,combinedlow-doseplainCTand

18FFDG-PETexaminationwasrepeated,whichshowedpro- gressionintheskinandthelymphnoderegions.Moreover, pericardial effusion (maximum thickness22 mm) andcar- diacinvolvementinthedorsalregion(multipleactiveﬁelds withthemaximumstandardizeduptakevalueof33.4)were also conﬁrmed,indicating lymphoma manifestation in the heart(Figure1).

No arrhythmias were detected, but the patient had symptomsof hypotonia andchest pain,aswellasanemia (hemoglobin:94g/l)andincreasedlactatedehydrogenase (1824 U/l) and troponin T (0.261 ␮g/l) levels, with nor- malcreatininekinase(62U/l).Urgentcoronaryangiography showed normal epicardial coronary arteries. Neurological symptoms including dizziness, blurred vision and altered mentalstatusindicatedcentralnervoussystemmanifesta- tionof thelymphoma.Plainnon-enhancedcranialCTwas performed, with a negative result. Lumbar puncture was alsoperformedandshowednosignsoflymphomainvolve- ment or infection. A new course of chemotherapy was started with rituximab and the BFM protocol (ﬁrst day:

vincristine 2 mg, methotrexate 3 g/m²; from day 1-5:

ifosfamide 800 mg/m²; day 4-5: cytosine arabinoside 2×150mg/m²anddexamethasone10mg/m²)forﬁvedays.

Clinically,thepatientis stable,butrequires morecourses ofchemotherapy.

As a part of her assessment, routine two-dimensional Dopplerechocardiographyand3DSTEwereperformedusing Toshiba Artida^TM ultrasound equipment with PST-30SBP phased-arrayandPST-25SXmatrixphased-arraytransducers (Toshiba MedicalSystems, Tokyo,Japan). Dataacquisition andevaluationofechocardiographicstudiesfollowedrecent guidelines and practices.⁸ Echocardiographic examination found normal atrial and ventricular dimensions and 50%

EF, with no wall motion abnormalities and with grade I diastolicdysfunction.ColorDopplerechocardiographycon- ﬁrmedgrade1mitralregurgitation.Pericardialeffusionwas detected,7-11mminsizenexttotheposterior,lateraland inferiorwallsand10-12mmaroundtherightapicalregion.

During3DSTEwithaframerateof27volumespersecond, reductioninsomesegmentalradial,longitudinal,circumferential,areaand3DLVstrainswerefound(Figure2).Apical andbasalLVrotationswerefoundtobeinthesamecoun- terclockwisedirection,conﬁrmingnearabsenceofLVtwist ---so-calledrigidbodyrotation(RBR).

The patient was enrolled in the MAGYAR-Path study (Motion Analysis of the heart and Great vessels bY three-dimensionAl speckle-tRacking echocardiography in Pathological cases) and had provided informed consent.

Thestudy protocol conformedtothe ethicalguidelinesof the1975Declaration ofHelsinki andwasapprovedbythe institution’shumanresearchcommittee.

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Figure2 Apical4-chamber(A)and2-chamber(B)viewsandshort-axisviews(C3,C5,C7)atdifferentlevelsoftheleftventricle (LV)extractedfromthethree-dimensional(3D)echocardiographicdatasetinthepatientwithdiffuselargeB-celllymphoma.The3D modeloftheleftventricleandcalculatedLVvolumetricandfunctionalcharacteristicsarealsopresentedtogetherwithLVrotational (D)andstrain(E)parameters.Apical(whitearrow),midventricularandbasal(dashedarrow)LVrotationsweredemonstratedtobe inthesamecounterclockwisedirection,conﬁrmingthenearabsenceofLVtwist(rigidbodyrotation).SomesegmentalLVstrains werealsofoundtobereduced.EDV:end-diastolicvolume;EF:ejectionfraction;ESV:end-systolicvolume;LV:leftventricular.

Discussion

Primarycardiac tumorsareextremely rare,witha preva- lenceof0.001-0.28%.^2,3Theincidenceofsecondarycardiac tumors varies from 2-18.3%.^2,10 Among secondary tumors, cardiacinvolvementbylymphoma isinfrequent, butinan autopsystudy of malignantlymphoma,cardiac metastasis wasfoundin16%ofcases.^2,11Lessthan5%ofcardiactumors are primary, and of these, only 1.3% are primary cardiac lymphoma.^12---15 Its incidence is higher in immunocompro- mised hosts, and B-cell lymphoma is the most common type.¹²

Despiteinvolvementofmyocardialtissue,cardiacsymp- toms may be absent or non-speciﬁc. Case reports seem toindicate that the heart is more often involved in non- Hodgkin’slymphoma,butpericardialmanifestationismore common in Hodgkin’s disease.^2,13 Cardiac lymphomas are usuallysmallandmultiple,sometimesfocalordiffuse,but tumorinﬁltrationsofthepericardium,myocardiumorendo- cardiumhavealsobeenobserved.Therightsideoftheheart hasbeenfoundtobemorefrequentlyinvolvedthantheleft side.²

Tothebestoftheauthors’knowledgethisistheﬁrsttime alterations in LV rotational mechanics have been demon- stratedinapatientwithPET/CT-provencardiaclymphoma.

The leftventricleconsistsof a3D helical structurewhich is responsible for cyclic twisting deformation in systole, resultingfromclockwiserotationoftheLVbaseandcoun- terclockwiserotationoftheLVapex.⁶Itisknownthataging appearedtoberelatedtoanincreaseinLVtwist,¹⁶ andin speciﬁcpathologicalcircumstancesLVrotationandtwistcan be altered. In particular, in recent studies LV basal rota- tionwasfoundtobemoderatelyincreasedinhypertrophic cardiomyopathy,but was reducedin non-ischemic dilated

cardiomyopathy duetoreductionin bothapical andbasal LVrotations.⁵

In the present case, both apical and basal LV regions moved in the same counterclockwise direction to a sim- ilar extent (a difference of about 6^◦), conﬁrming the near absence of LV twist (RBR). RBR has previously only been demonstrated in a limited number of disorders, including cardiomyopathies (peripartum,¹⁷ hypertensive,¹⁸ dilatedwithreducedEF¹⁹andnoncompaction²⁰),inﬁltrative disorders(amyloidosis)²¹andcongenitalheartdisease(uni- ventricularheart²²andhypoplasticrightheartsyndrome²³).

Theunderlyingmechanismisunknown,butthefindingspre- sentedcouldbeexplainedbyinfiltrationofthemyocardium bylymphomatissue,asconfirmedinsomeareasbyPET/CT.

As the basic principle of PET is the increased glycolysis characteristicoftumors,whichconsumemoreglucosethan normaltissue,thedamagecausedbychemotherapyshows upasanegativechangeonPET.ThusthePET/CTresultand the3DSTEresultareidentical,whichprovesthatinthiscase thelesionsareduetothelymphomaandnottocardiotoxic effects.

Further studies are needed to conﬁrm our ﬁndings in largerpatientpopulationsfocusingonthepathomechanism, clinicalrelevanceandimplicationsofLVRBRandonpossible treatmentoptions.

Ethical disclosures

Protection of human and animal subjects.The authors declare that the proceduresfollowed werein accordance withtheregulationsoftherelevantclinicalresearchethics committeeandwiththoseoftheCodeofEthicsoftheWorld MedicalAssociation(DeclarationofHelsinki).

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Conﬁdentialityofdata.Theauthorsdeclarethattheyhave followedtheprotocolsoftheirworkcenteronthepublica- tionofpatientdata.

Righttoprivacyandinformedconsent.Theauthorshave obtained the written informedconsent of thepatients or subjectsmentionedinthearticle.Thecorrespondingauthor isinpossessionofthisdocument.

Conﬂicts of interest

Theauthorshavenoconﬂictsofinteresttodeclare.

Acknowledgments

Financialsupport: Thisresearchreceivednospeciﬁcgrant fromanyfundingagency,commercialornot-for-proﬁtsec- tors.

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