Left ventricular assessment in patients with mucopolysaccharidosis using conventional

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www.jped.com.br

ORIGINAL ARTICLE

Left ventricular assessment in patients with mucopolysaccharidosis using conventional

echocardiography and myocardial deformation by two-dimensional speckle-tracking method ^夽,夽夽

Mirela F.A. Andrade

^a^,∗

, Isabel Cristina B. Guimarães

^b

, Angelina X. Acosta

^c

, Emília Katiane E.A. Leão

^c

, Moisés I.G. Moreira

^d

, Carlos Maurício C. Mendes

^a

aUniversidadeFederaldaBahia(UFBA),ProgramadePósGraduac¸ãoemProcessosInterativosdosÓrgãoseSistemas(PPGPIOS), Salvador,BA,Brazil

bUniversidadeFederaldaBahia(UFBA),FaculdadedeMedicina,DepartamentodePediatria---SetordeCardiopediatria,Salvador, BA,Brazil

cUniversidadeFederaldaBahia(UFBA),FaculdadedeMedicina,DepartamentodePediatria---SetordeGenética,Salvador,BA, Brazil

dUniversidadeFederaldaBahia(UFBA),FaculdadedeMedicina,HospitalUniversitárioProfessorEdgardSantos(HUPES), Salvador,BA,Brazil

Received23October2017;accepted18April2018 Availableonline27June2018

KEYWORDS Mucopolysaccharido- sis;

Echocardiography;

Cardiacfunction tests;

Enzymereplacement therapy

Abstract

Objective: Mucopolysaccharidosisisararegeneticdiseasecharacterizedbytheintralysosomal deposition ofglycosaminoglycans. Cardiovascular impairmentisa commonfeature. Cardiac signsandsymptomsareunderestimatedduetothediseaseinvolvementinotherorgans.Enzyme replacementtherapycanbeusedinmucopolysaccharidosisI,II,IV,andVI.Thus,theknowledge abouttheuseofnewechocardiographytoolsisrelevanttoimprovethecareofthispopulation.

Thisstudyaimedtodescribeleftventricularfunctionassessmentbyconventionalechocardi- ographyandleftventriculargloballongitudinalstrainanalysisandcomparethealterationsin patients receiving enzymereplacementtherapyandwho haddifferent agesatthe startof therapy.

Method: Outpatient-based descriptive study. The patients were submitted to conventional echocardiographyandleftventriculargloballongitudinalstrainmeasurement.

夽 Pleasecitethisarticleas:AndradeMF,GuimarãesIC,AcostaAX,LeãoEK,MoreiraMI,MendesCM.Leftventricularassessmentinpatients withmucopolysaccharidosisusingconventionalechocardiographyandmyocardialdeformationbytwo-dimensionalspeckle-trackingmethod.

JPediatr(RioJ).2019;95:475---81.

夽夽Thisarticleis partoftheMaster’sDegreedissertationofDr.MirelaFredericodeAlmeida Andrade throughtheProgramade Pós- Graduac¸ãoemProcessosInterativosdosÓrgãoseSistemas,InstitutodeCiênciasdaSaúde,UniversidadeFederaldaBahia(UFBA),Salvador, BA,Brazil.

∗Correspondingauthor.

E-mail:[email protected](M.F.Andrade).

https://doi.org/10.1016/j.jped.2018.05.006

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Results: Sixteenpatientswereevaluated;medianageof14.2years(SD=5.2years).Leftventri- cularhypertrophywasfoundinninepatients(56.2%).Allpatientshadpreservedleftventricular systolic function (Simpson and Teichholz). Nine (56.2%) patients showed alterations in left ventricular globallongitudinalstrain. Thestudy showed apositive associationbetween left ventricularhypertrophyandalterationintheleftventriculargloballongitudinalstrain,andlate startofenzymereplacementtherapyandalterationintheleftventriculargloballongitudinal strain.

Conclusion: Echocardiographic alterationsinpatients with mucopolysaccharidosis were frequently observed, especially alterations in the left ventricular geometry and subclinical dysfunction. Patientswhohadalate enzymereplacementtherapystartshowedanassocia- tionwithworseleftventriculargloballongitudinalstrainvalues,reinforcingtheneedforearly diagnosisandtreatment.Theuseofnewechocardiographictoolsmayimprovethefollow-up ofthesepatients.

4.0/).

PALAVRAS-CHAVE Mucopolissacaridose;

Ecocardiograﬁa;

Testesdefunc¸ão cardíaca;

Terapiadereposic¸ão enzimática

Avaliac¸ãodoventrículoesquerdoempacientescommucopolissacaridoseatravésdo ecocardiogramaconvencionaledadeformac¸ãomiocárdicapelospeckle-tracking bidimensional

Resumo

Objetivo: A mucopolissacaridose é uma doenc¸a genética rara, caracterizada por depósito intralisossômico de glicosaminoglicanos. O comprometimento cardiovascular é frequente.

Sinaisesintomascardíacossãosubestimadospeloenvolvimentodadoençaemoutrosórgãos.A terapiadereposiçãoenzimáticapodeserusadaemmucopolissacaridoseI,II,IVeVI.Assim,o conhecimentodaaplicaçãodenovasferramentasdeecocardiografiaérelevanteparamelhorar aassistênciadessapopulação.Esteestudo visoudescrever afunçãodo ventrículoesquerdo peloecocardiogramaconvencionalepela análisedostrainglobal longitudinaldo ventrículo esquerdo e comparar as alterações em pacientes que fazem uso da terapia de reposição enzimáticaequetiveramidadesdistintasdeiníciodaterapia.

Método: Estudodescritivodebaseambulatorial.Ospacientesforamsubmetidosàecocardio- graﬁaconvencionalemedidadostraingloballongitudinaldoventrículoesquerdo.

Resultados: Foramavaliados16pacientes;medianade14,2anos(desvio:5,2anos).Hipertrofia doventrículoesquerdofoiencontradaemnovepacientes(56,2%).Todosospacientestiveram função sistólica do ventrículo esquerdo preservada (Simpson e Teichholz). Nove (56,2%) pacientesapresentaramalteraçãonostraingloballongitudinaldoventrículoesquerdo.Oestudo mostrou associação positiva entre hipertrofia do ventrículo esquerdoe alteração no strain globallongitudinaldoventrículoesquerdoeiníciotardiodaterapiadereposiçãoenzimáticae alteraçãonostraingloballongitudinaldoventrículoesquerdo.

Conclusão: Alterações ecocardiográficas em pacientes com mucopolissacaridose foram fre- quentes,especialmentealteraçõesnageometriaedisfunçãosubclínicadoventrículoesquerdo.

Pacientes que iniciaram tardiamente a terapia de reposição enzimática apresentaram associação com piores valores de strain global longitudinal do ventrículo esquerdo, o que reforçaanecessidadedodiagnósticoetratamentoprecoces.Ousodenovasferramentasde ecocardiografiapodemelhoraroacompanhamentodessespacientes.

0/).

Introduction

Mucopolysaccharidosis(MPS)isararegeneticdisease,witha worldwideincidencerateof1:25,000births.Itischaracter- izedasalysosomaldepositiondiseaseduetotheabsenceof aspeciﬁcenzymethatdegradesglycosaminoglycans(GAG), polymers that constitute themembrane and extracellular matrix. Thus, its intra- and extracellular accumulation is

capable of generating dysfunction in several organs and tissues. There are seven types of MPS, and 11 enzymatic defectshavebeendescribed,witheachtypebeingcharac- terizedbythedeﬁciencyofaspeciﬁcenzyme.¹

One of the frequently affected systems in MPS is the cardiovascularsystem. This impairmentis progressiveand limitspatient qualityof life,being considered oneof the main causes of death in this population due to cardiac

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alterations caused by the accumulation of GAG in heart structures, such as valvular lesions,myocardial hypertrophy,coronaryimpairment,pulmonaryhypertension,cardiac rhythmdisorders,andsystolicanddiastolicdysfunctions.² Thecardiovascularsymptomsandsignsarescarcebecause of the disease involvement in the respiratory and skele- talsystems,factorsthatlimitclinicalevaluationregarding physicalactivitytolerance---asignofheartfailure.Thecog- nitive deﬁcit present in some types of MPSalso makesit difﬁcultforthepatienttoperceivecardiacsymptoms.Enzy- maticReplacementTherapy(ERT)canbeusedinMPStype I,II,IV,andVI;itseffectoncardiacalterationsisstillbeing studied.Hencetheimportanceofimagingfollow-upthrough echocardiographyaimingtopromotetheearlydetectionof cardiovascularalterations.³

The measurement of the myocardial strain through 2- Dimensional Speckle-Tracking Echocardiography (2D-STE) has been described in the literature as an accurate tool for detecting incipientmyocardial injury,being important intheearlydiagnosisofsubclinicalcardiacdysfunctionand prognosisinseveralheartdiseases.⁴

The study aimed to describe left ventricular function throughconventionalechocardiographicmeasurementsand alsobyLeftVentricular(LV)GlobalLongitudinalStrain(GLS) analysisby2D-STEinpatientswithMPS,andcomparedthe alterationsfoundintheLVGLSinpatientswhoreceivedERT andwhostartedthetherapyatdifferentages.

Methods

Studydesignandpatients

This wasa descriptive, cross-sectional, ambulatory-based studywithoutacomparativegroup,carriedoutinpatients with MPS (enzymatic diagnosis) followed at the Genetics OutpatientClinicofHospitalUniversitárioProfessorEdgard Santos of Faculdade deMedicina da UniversidadeFederal daBahia(HUPES---UFBA).The inclusioncriterionwasthat thepatientmusthaveattendedatleastoneconsultationat the Genetics Outpatient Clinicfrom January 2015 toMay 2016. The exclusion criteria were presence of congenital heartdiseaseor complicationduringtheexamination.The study wasapproved bythe ResearchEthics Committeeof InstitutodeCiênciasdaSaúdedaUFBAinaccordancewith theDeclarationofHelsinki,andallparticipantsorpatients’

legalguardianssignedtheinformedconsent.

Echocardiography

All patients were evaluated by the same echocardiogra- pher, whowasblinded tothe patients’clinical condition.

The exams were performed using the iE33 (Philips Medi- cal Systems --- Andover, MA, USA) apparatus with 5 and 8MHztransducersandfollowingtherecommendationsofthe AmericanSociety of Echocardiography.The patients were atrest andwithoutsedation; electrocardiogramrecording wasperformedconcomitantlywiththeexaminationandall assessedpatientswereatan adequateheartratefor age, withnoepisodesofarrhythmia.

Conventionalechocardiography

LV mass --- it was calculated through the linear method (measurementsoftheinterventricularseptum,LVinternal diameter,andleftventricularposteriorwallthicknesswere performed at the end of diastole) andindexed by height raisedtotheexponentialpowerof2.7(LVMI).Normalval- uesforindexedmass:boysolderthan9years≤45g/m^2.7and girlsolderthan9years≤40g/m^2.7.Inchildrenyoungerthan 9years,valuesabovethe95thpercentilewereconsidered altered(hypertrophy).⁵

LVsystolicfunction---itwasevaluatedbycalculatingthe ejectionfraction(EF)usingtwoparameters:

a) Simpson’smethod---normalfunctionwhen≥52%formen and≥54%forwomen.⁶

b) Teichholzformula---normalfunctionwhenvalue≥55%.⁷ LVgloballongitudinalstrain

Left ventricular(LV) global longitudinal strain (GLS) mea- surementswereperformedaccordingtotheprotocolofthe AmericanSociety of Echocardiography.⁶ Videos withgood electrocardiographic tracing and approximately 60 to 80 framespersecondwereacquiredinatleastthreeconsec- utivecardiac cycles(none ofthe patients hadarrhythmia during the examination). Stored videos should have good imagingquality.Theanalyseswereperformedofﬂine,using QLAB(PhilipsMedicalSystems---Andover,MA,USA)software.

The endocardial borders were demarcated by the equip- ment,throughthesequenceofthreepointsdeﬁnedbythe researcherintheendocardium.Finecontouradjustmentof theendocardialborders wasperformed bytheresearcher.

Allpatientshadsatisfactoryimagesofthecardiacsegments.

For the evaluation of the LV GLS, videos were recorded ofthreeechocardiographic windows(four, three,and two chambers).Thevalueobtainedthroughtheaverageofthe threesliceswasconsideredtobetheLVGLS.

Referencevaluesinchildren(youngerthan21years)fol- lowedthoserecommendedbyLevy etal. in2016.⁸ As for patientsolderthan21years,thereferencevaluesfollowed thoserecommendedbyLangetal.⁶

Statisticalanalysis

As this is a descriptive study performed in a restricted population,thestatisticalanalysiswasperformed through descriptivestatisticsrelevanttothelevelofmeasurement of constant variables. Spearman’s correlation coefﬁcient wasusedfortheconstantcomparisons.

Inter- and intraobserver reliability assessments were performed for LV GLS measurements. Five patients were randomly selected. The evaluations were performed one month after data collection wascompleted. Forinterob- serverevaluation,thesecondinvestigatorperformedtheLV GLSmeasurementsoffline,withoutpriorknowledgeofthe previousechocardiogram.Fortheanalysisofthisevaluation, theIntraclass CorrelationCoefficient (ICC)and respective 95%ConfidenceIntervals(95%CI)wereused(forthequanti- tativevariables).⁹Inferentialstatisticswerenotcalculated (exceptfor theICC),sincethesamplingplanincludedthe

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Table1 DistributionofleftventricularfunctionbyconventionalechocardiographyaccordingtoMPStype.

Type n Teicholz(%) Median(IQI) Min---max Simpson(%) Median(IQI) Min---max

I 3 75 12 60.6---84.5 74 6.0 62---74

II 4 63.9 14.6 57---77.7 60.5 4.2 58---66

III 1 62.5 (---)^a 75 (---)^a

VI 8 69.9 11.1 57---85.3 67.5 3.0 59---70

Total 16

MPS,mucopolysacardiosis;n,numberofpatients;EF,ejectionfraction;IQI,interquartileinterval;min---max,minimum---maximum.

aSinglevalue.

assessmentofallpatientsenrolledintheoutpatientclinic andwhoattendedatleastoneconsultationatthegenetics outpatientclinicfromJanuary2015toMay2016.Thedata wereenteredintoEpidatasoftwareandtheanalyseswere performedusingthestatisticalpackageR,version3.1.¹⁰

Results

Thepresentstudyidentiﬁed20patientswithMPSwhowere followedattheHUPES/UFBAGeneticsOutpatientClinicand whoattendedat leastoneconsultationfromJanuary2015 toMay2016.Ofthistotal,twopatientswerenotincluded:

onedue torefusaltoparticipateinthestudy andanother fornot havingattendedthe cardiologicalevaluationafter fourattemptstoscheduleit,duetothepresenceofupper airwayinfectiononthefourscheduleddates.

Eighteenpatientsweresubmittedtocardiacevaluation, twoofwhomwereexcludedfromthestudy:oneduetoa diagnosisofcongenitalheartdisease(PatentDuctusArterio- sus---PDA)andanotherduetothepresenceofacomplication duringthe examination (seizure).The patient witha PDA diagnosis was referred to a pediatric cardiology referral service in the state of Bahia for heart defect correction.

Thus,thepresentstudyevaluated16patients.

Themedianageofthegroupwas14.2years,withaSD of5.2years(1.5---22.6),ofwhom12(75%)weremales.Five patients(31.2%)werefromthemunicipalityofSalvadorand itsmetropolitanregion,andtheothersfromthecountryside ofthestate,mainlyfromtheMonteSantoregion(56.2%),a municipalitywithahigh incidenceofgeneticdiseasesdue tothehighrateofconsanguineousmarriages.¹¹Themedian ageatthestartofERTwas8years(SD=4.5years)(1---14).

The following distributionwas observed regarding MPS types:3(18.8%)patientswithMPStypeI,4(25%)patients withMPStypeII,1(6.2%)withMPStypeIII,and8(50%)with MPStypeVI.

PatientswithMPStypesI,II,IV,andVIcanreceiveERT.

Ofthe15patientsbelongingtooneofthesefourgroups(I, II,andVI),14usedERTatthetimeoftheechocardiographic evaluation.OnlyonepatientfromgroupI,whounderwent theevaluationinthesamemonthinwhichtheMPSdiagnosis wasattained,didnotuseERTatthetimeoftheevaluation.

Leftventriculargeometry

Thestudyidentiﬁed9(56.2%)patientswithLeftVentricular MassIncrease(LVMI).

Leftventricularsystolicfunctionbyconventional echocardiography

The presentstudy evaluatedleftventricularsystolicfunc- tion by conventional echocardiography, considering the following parameters:SimpsonandTeichholz methods.All patientsevaluatedinthisseriesofcaseshadnormalleftven- tricularsystolicfunctionaccordingtothesetwoparameters (Table1).

2D-STE

Intra- and interobserver reproducibility analysis was performed regarding the LV GLS measurements, through calculation oftheICC,and ahighlevel ofagreementwas found. For the intraobserver reproducibility analysis, the ICCwasfoundtobe0.95(95%CI:0.58---0.99);andtheinter- observerICCwasfoundtobe0.94(95%CI:0.66---0.99).

TheLV GLSanalysis showedthat56.2% ofthe assessed patientshadalteredmeasurements(Table2).The median valuewas19%(SD=2.2,13%---22%).

Associationbetweenleftventricularmassand globallongitudinalstrain

This studyshowedthat patientswithalteredLVGLSmea- surementshadhigherLVMIvaluesthanpatientswithnormal LVGLSvalues.Apositivecorrelation(rs=0.502)wasfound betweenthesetwoparameters,asshowninFig.1.

Associationbetweentimeofenzymereplacement therapystartandleftventricularglobal

longitudinalstrain

PatientswhohadalteredLVGLSvalueshadalaterERTstart (patientswithMPStypesI,II,andVI).

The study showed a positive correlation (rs=0.320) betweentimeofERT startandLVGLSvalues,asshown in Fig.2.

Discussion

In 2013, Brands et al. studied the effects of ERT on 24 patientswithMPStypesI,II,andVI,andfoundthat70%of thosewhohadleftventricularmassincrease(12patients, i.e.,50%oftheassessedindividuals),hadLVMInormalization afteratleastoneyearofERT.¹²

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Table2 DistributionofleftventricularGLSaccordingtoMPStype.

Type n LVSGL

Normal Altered Median(%) IQI Min---max

I 3 1 2 19.0 2.0 18---22

II 4 1 3 17.5 2.5 13---20

III 1 1 0 20.0 (---)^a

VI 8 4 4 19.5 2.5 15---22

Total 16 7 9

GLS, global longitudinalstrain;MPS, mucopolysacardiosis; n, numberof patients;EF, ejection fraction;IQI, interquartileinterval;

min---max,minimum---maximum.

a Singlevalue.

A B

80

70

60

50

40

Yes No

LV indexed mass (g/m^2,7) LV indexed mass (g/m27)

30

20

Altered strain

80

70

60

50

40 rs=0.525

30

20

Spearman’s correlation

12 14 16

LV strain values

18 20 22 24

Figure1 Associationbetweenleftventricularmassandgloballongitudinalstrain.(A)Box-plot(qualitativestrain);(B)correlogram (quantitativestrain).

Time of ERT onset (years) LV strain values

Yes No

Altered strain

Time of ERT onset Spearman's correlation

rs = 0.32**

14

12

10

8

6

4

2

22

20

18

16

14

12

0 5 10 15

A B

Figure2 Associationbetweenthe timeofERT onsetandleft ventricularglobal longitudinalstrain. (A)Box-plot(qualitative strain);(B)correlogram(quantitativestrain).

Lin etal.studied patients withMPStypes I,II, IV,and VI who used ERT. After one year of enzymatic therapy, a statistically signiﬁcant (p<0.01) reduction of LVMI was observedinpatientswhostartedERTbefore12yearsofage (74.7g/m²±21beforeERTand54.4g/m²±18.9afterERT).

ThiseffectwasnotevidentinpatientswhostartedERTafter theageof12years.¹³

These studies suggest that ERT is able to reduce left ventricular hypertrophy secondary to MPS by a probable reduction in GAG accumulation in the cardiac muscle,

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especiallyifinitiatedearly.Thepresentstudyshowedthat 9(56.2%)patientshadleftventricularhypertrophy.Median age at the start of ERT was 8 years. This fact possibly contributed to the high percentage of patients with left ventricularhypertrophy.

Thestudyanalyzedleftventricularsystolicfunctionusing twoconventionalechocardiographicvariables:Simpsonand Teichholz.Noneoftheassessedpatientshadleftventricu- lar systolic dysfunction by any of these parameters. This resultwasconsistent withother studies in theliterature:

Lealetal.,in2010,studiedchildrenwithMPSwithoutERT useandLinetal.,in2016,studiedpatientswithMPStypes I,II,IV,andVIbeforeandafterERTuse.ADutchstudy,in 2013,showedareductioninleftventricularsystolicfunc- tionin3(12.5%)of24patientsstudiedbeforethestartof ERT (MPS types I,II, and VI).After one year of ERT, two patientsshowednormalfunctionandonlyonemaintained systolicdysfunction,whichwasthesamepatientwhoalso maintaineddiastolicdysfunctioninthesamestudy.^12---14

ThepresentstudyevaluatedLVGLSandveriﬁedthat,of the16assessedpatients, 56.2%hadalteredGLSmeasure- ments.Theliteratureisscarceregardingtheevaluationof thisparameter in patients withMPS. Few studies todate haveusedmyocardial strainmeasurement asaparameter ofventricularfunctioninthispopulation.

In 2011, Harada et al. described the case of a 49 year-old woman with MPS type I before and after six months of enzyme replacement therapy with laronidase.

Therewasan improvementintheLVGLSvalueduringthe period(13.2%---17.4%), whereastheejectionfractionmea- sured by conventional echocardiography did not change.

Additionally,thepatientshowedleftventricularmassreduc- tion(189---152g),reductionin glycosaminoglycan levelsin urine (75---38mg/g of creatinine), and reduction in hep- atosplenomegaly(evaluatedbycomputedtomography).¹⁵

In2014,Leeetal.performedan experimentalstudyin geneticallymodiﬁedmicewiththemodelofcardiomyopa- thyassociatedwithHuntersyndrome(MPStypeII),before and after the use of ERT, and observed cardiac function improvement according tothe circumferential and radial strain measurements at the end of the analyzed period (9.44%---12.41%and16.91%---28.91%,respectively).¹⁶

In 2013, a Canadian study evaluated left ventricular systolic function through conventional echocardiography andmyocardialstrainby2-dimensionalspeckletrackingin patientswithFabrydisease,amultisystemicdepositiondis- ease(suchasMPS) due togalactosidaseA deﬁciencythat canresultinsequelae inseveralorgansandsystems,such as the kidneys, brain, and heart, due to protein deposi- tionintissues. All16 studiedpatients hadbeen receiving enzyme replacementtherapy for a periodlongerthan six years.Allpatientshadnormalleftventricularsystolicfunc- tionmeasuredthroughEFmeasurement(meanof63%),but the study reported a reduced mean LV GLS value in this population(16%),suggestingthatthismeasureismoresen- sitivetotheevaluationofsystolicfunctioninthisgroupof patients.¹⁷

AnItalianstudyin2017evaluatedconventionalechocar- diographic aspects and myocardial deformation measures bytwo-dimensionalspeckle-trackingin15patientswithMPS (typesI,II,III,IV,andVI)andcomparedthemwithhealthy controls. Ten patients were receiving ERT (mean: 6.5

years).MPSpatientsshowedincreasedvaluesofventricular mass when compared to controls. All patients with MPS had adequate ventricular systolic function measurements by conventional echocardiography (Simpson) without any differenceregardingthevaluesfound inpatientsfromthe controlgroup.PatientswithMPShadareductioninglobal radialandcircumferentialstrainmeasurementsinrelation tocontrols.Suchadifferencebetweenthetwogroupswas not observed for theglobal longitudinal strain.The study doesnotdescribetheageatthestartofERTinthestudied population, only the average of use. Difference in this parametercouldbeaprotectivefactorinthelongitudinal myocardial ﬁbers. More studies are required to better evaluate the changes in the three types of myocardial ﬁberdeformation(longitudinal,radial,andcircumferential strain)inpatientswithMPS.¹⁸

Thepresentstudyverifiedapositiveassociationbetween alterationsintheLVGLSandleftventricularmass.Addition- ally,thelatestartofERTalsoshowedapositiveassociation withalteredvaluesofLVGLS.Possibly,thelatestartofthe enzyme replacement therapy may lead to increased GAG depositionandfurthercardiacsequelae,whichjustifiesthis subclinicaldysfunctionfindingatthestrain.

Thepresentstudyshowedsigniﬁcantcardiacalterations in patients with MPS, corroborating the importance of the cardiological follow-up in this population. Moreover, patientswhohadalateERTstartshowedanassociationwith worsevaluesofLVgloballongitudinalstrain,reinforcingthe needforanearlydiagnosisandtreatment.

Becauseit isa raregeneticdisease, theresults of the presentstudyarelimitedtoasmallnumberofpatientswith MPS,anditisnotpossibletoconsideralldescribedtypesof thepathology.

Manypatientshadthoracicdeformitiesduetotheimpair- mentcausedbythediseaseitself,whichresultedingreater technicaldifﬁcultyduringtheexams.Becausethedatawere collectedataspeciﬁctimeforthestudyperformance,not concomitantly withthe echocardiographyservice routine, theresearcherwasabletocalmlyseekthebestechocardi- ographicwindowineach patient,thusminimizing possible measurementbiases.

This study used new echocardiography tools in the assessment of patients withMPS, a systemic diseasewith progressive cardiac involvement. These techniques have beenshowntoreﬁnethecardiovascularfollow-upofthese patients,thus makingit possible,togetherwiththetradi- tionalandconventionaltechniques,toimprovethediagnosis ofcardiacsequelaeandtoanticipatepossibleinterventions.

Conﬂicts of interest

Theauthorsdeclarenoconﬂictsofinterest.

Acknowledgements

ToDr.GabrielaNunesLeal,whoseMaster’sdegreedisserta- tioninspiredthisstudy.Thankyouforyourconstantsupport duringtheperformanceofthisproject.

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Left ventricular assessment in patients with mucopolysaccharidosis using conventional

ORIGINAL ARTICLE