MAGYAR-Path Study three-dimensional speckle-trackingechocardiographic ventricular contractility: Results fromthe Active acromegaly is associated with enhancedleft Cardiologia

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www.revportcardiol.org

Revista Portuguesa de

Cardiologia

Portuguese Journal of Cardiology

ORIGINAL ARTICLE

Active acromegaly is associated with enhanced left ventricular contractility: Results from

the three-dimensional speckle-tracking echocardiographic MAGYAR-Path Study

Árpád Kormányos

^a

, Péter Domsik

^a

, Anita Kalapos

^a

, Nándor Gyenes

^a

, Zsuzsanna Valkusz

^b

, Csaba Lengyel

^b

, Tamás Forster

^a^,^b

, Attila Nemes

^a^,∗

a2ndDepartmentofMedicineandCardiologyCentre,MedicalFaculty,AlbertSzent-GyörgyiClinicalCenter,UniversityofSzeged, Szeged,Hungary

b1stDepartmentofMedicine,MedicalFaculty,AlbertSzent-GyörgyiClinicalCenter,UniversityofSzeged,Szeged,Hungary

Received7October2018;accepted1August2019 Availableonline26May2020

KEYWORDS Acromegaly;

Echocardiography;

Function;

Leftventricle;

Three-dimensional speckletracking

Abstract

Introduction:Acromegalyisarelativelyrarechronichormonaldisease resultingindisﬁgure- ment.In90%ofcases,acromegalyiscausedbyabenignpituitarymonoclonalhumangrowth hormone-secretingtumor.Theaimofthepresentstudywastodeterminethepresenceofleft ventricular(LV)deformationabnormalitiesusingthree-dimensionalspeckle-trackingechocar- diographyinagroupofacromegalicpatients.

Methods:Thirty-eight acromegalic patients were involved in the study. Thirteen patients were excluded due to inadequate image quality. The mean age ofthe remaining patients was 57.2±13.6 years and seven were male. Their data were compared to an age- and gender-matched control population, which consisted of 34 healthy volunteers (mean age:

52.7±4.9years,15male).

Results:GlobalandmeansegmentalLVradialstrain(RS)(33.2±13.4%vs.25.2±10.8%,p=0.01 and 36.0±12.1% vs. 28.2±10.0%, p=0.009, respectively) proved to be signiﬁcantly higher in acromegaly compared to controls. Active acromegalic patients had signiﬁcantly higher global andmean segmental LV-RS (35.5±14.4% vs. 25.2±10.8%,p=0.03 and 37.9±13.3% vs.

28.2±10.0%, p=0.03, respectively) compared to controls. Between the active and inactive acromegalygroups,onlybasal LVcircumferentialstrain(-30.2±4.8%vs.-26.7±4.1%,p=0.02) wasfoundtobesigniﬁcantlydifferent.

∗Correspondingauthor.

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

https://doi.org/10.1016/j.repc.2019.08.010

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Conclusion:Thepresentedclinical,demographic,therapeuticandechocardiographicfeatures demonstratethatactiveacromegalyisassociatedwithenhancedLVRSascomparedtohealthy controlsandthosewithinactiveacromegaly.

PALAVRAS-CHAVE Acromegalia;

Ecocardiograﬁa;

Func¸ão;

Ventrículoesquerdo;

Speckletracking tridimensional

Associac¸ãoentreacromegaliaativaecontractilidadeventricularaumentada:

resultadosdoEstudoMAGYAR-Pathcomecocardiograﬁatridimensionalporspeckle tracking

Resumo

Introdução:A acromegalia éuma doençahormonal crónicarelativamente rara,associadaa dismorfismossomáticos.Em 90%doscasos,ela écausadaporumtumorbenignomonoclonal dahipófise, secretorde hormonado crescimento. Oobjetivo dopresente estudo foidete- tarapresençadealteraçõesdadeformaçãomiocárdicadoventrículoesquerdo(VE)através deecocardiografia tridimensionalporspeckle trackingnumgrupodedoentesportadores de acromegalia.

Métodos: Foramincluídos38doentesportadoresdeacromegalia.Trezeforamexcluídosdevido àmáqualidadedeimagem.Aidademédiadosrestantesfoide57,2±13,6anos(7homens).Os seusdadosforamcomparadoscomumapopulac¸ãocontroloemparelhadaporidadeegénero, quecompreendeu34voluntáriossaudáveis(idademédia:52,7±4,9anos,sendo15indivíduos dosexomasculino).

Resultados: Ostrain radial(SR) global e segmentar VE (respetivamente 33,2±13,4% versus 25,2±10,8%,p=0,01e36,0±12,1%versus28,2±10,0%,p=0,009)foisignificativamentesuperior noscasosdeacromegaliaem relaçãoaoscasoscontrolo.Osdoentesportadoresdeacrome- galiaativativeramumSRglobalesegmentarsignificativamentesuperior(35,5±14,4%versus 25,2±10,8%,p=0,03e37,9±13,3%versus28,2±10,0%,p=0,03,respetivamente),quandocom- paradoscomosgruposcontrolo.Entreosgruposportadoresdeacromegaliaativoseinativos, sófoiconsideradosignificativamentediferenteostraincircunferencialbasalVE(-30,2±4,8%

versus-26,7±4,1%,p=0,02).

Conclusões:Combasenascaracterísticasclínicas,demográficas,terapêuticaseecocardiográ- ficasapresentadas,aacromegaliaativaapresentaSR-VEaumentadoemrelaçãoàpopulação saudáveleaogrupodeportadoresdeacromegaliainativa.

Introduction

Acromegaly is a relatively rare chronic hormonal disease resultingin disﬁgurement. In 90% of cases, acromegaly is caused by a benign pituitary monoclonal human growth hormone (HGH)-secreting tumor.¹ Elevation of serum HGH causes an elevation in insulin-like growth factor 1 (IGF-1),and these hormonalchanges cause a wide range ofclinicalsymptomsandcomorbiditiesincludingmetabolic, respiratory,otherendocrineandcardiovasculardiseases.^2,3 Ofthesecardiovascularcomorbidities,hypertensionandleft ventricular (LV) hypertrophy are the most common, but serious valvular regurgitation and heart failure can also develop. A higherincidence of cardiac arrhythmias,most commonlyatrial ﬁbrillation,has frequentlybeen reported inacromegaly.^4,5

Three-dimensional(3D)speckle-trackingechocardiography (STE) (3D-STE) is a new, non-invasive, robust and

validated tool offeringclinicians a newimaging modality.

3D-STE is capable of measuringvarious global, segmental and regional strain values throughLV modeling.^6,7 To the best of the authors’ knowledge, there have been no 3D- STEstudiesonLVdeformationabnormalitiesinacromegaly.

Therefore,theaimofthepresentstudywastodetermine thepresenceofLVdeformationalabnormalitiesusing3D-STE inagroupofacromegalicpatients.

Methods

Patientpopulation

Thirty-eight acromegalic patients were included in the present study.Thirteen wereexcluded due toinadequate image quality. The mean age of the remaining patients was 57.2±13.6 years and seven were male. Their data were compared to an age- and gender-matched control

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population,whichconsistedof34healthyvolunteers(mean age52.7±4.9years,15male).Thediagnosisofacromegaly was based on current clinical standards: typical clinical features, elevated HGH levels, and elevated IGF-1 levels insuppressible with an oral glucose tolerance test.⁵ The acromegalicgroupwasfurtherdividedbasedontheactiv- ityofthedisease:ifserumHGHand/orIGF-1concentration wasoverthediagnosticthreshold,acromegalywasconsid- eredtobeactive.^5,8Ourstudywasapprovedbythehuman researchethicscommittee ofourinstitutionandcomplied with the Declaration of Helsinki. All of the patients and healthyvolunteersgaveinformedconsent.Ouracromegalic datasetscamefromtheMAGYAR-PathStudy(MotionAnalysis oftheheartandGreatvesselsbYthree-dimensionAlspeckle- tRackingechocardiographyinPathologicalcases),whichwas developedtoassessthediagnosticandprognosticvalueof 3D-STE-derivedparameters(‘Magyar’means‘Hungarian’in theHungarianlanguage).

Two-dimensionalDopplerandtissueDoppler echocardiography

Allhealthyvolunteersandacromegalicpatientsunderwent a complete two-dimensional (2D) transthoracic echocardiographic study using a Toshiba Artida^TM imaging system

(ToshibaMedicalSystems,Tokyo,Japan) withaPST-30SBP phased-arraytransducer(1-5MHz).Theexaminationswere performed according to current clinical standards. In all casesLVdimensions,volumes andejectionfraction(LVEF) andleftatrial(LA)dimensionsweremeasuredandcomplete 2DDopplerandtissueDopplerstudieswereperformed.⁹

Three-dimensionalspeckle-tracking echocardiography

Forthe3D-STEexaminations,thesameToshibaArtida^TMsys- tem was used, with a PST-25SX matrix- array transducer (ToshibaMedical Systems,Tokyo,Japan).⁷ In eachcase, a pyramid-shapedfull-volume3D datasetwasobtained.The complete dataset consisted of six wedge-shaped subvol- umes, which wererecorded during six RRintervals and a singlebreath-hold.Thesubvolumesweresettobeasnar- rowaspossibletoimprovespatialresolution,thusimproving laterendocardialborderdelineation.Therecordeddatasets were analyzed ofﬂine using the supplied 3D Wall Motion Tracking software, version 2.7 (Toshiba Medical Systems, Tokyo,Japan).Fromthedatasets, thesoftwareautomati- callyreconstructedapical4-chamberand2-chamberviews, thenthe readerspeciﬁed thethreecross-sectional planes manually, using the guide planes to help standardize LV

Figure1 Three-dimensionalspeckle-trackingechocardiographicstudyofanacromegalicpatient.Apical4-chamberview(A)and apical2-chamberview(B)areautomaticallyselectedbythesoftware.Cross-sectionalplanesareattheapical(C3),midventricular (C5)andbasal(C7)leftventricular(LV)levels.Thethree-dimensionalLVmodel(D)andthecorrespondingvolumetricparameters (E)areshownalongwithsegmentalLVradialstraincurves(F).

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measurements.Aftersettinguptheplanes,thereaderthen speciﬁed the septaland lateral parts of the mitralannu- lusandtheLVapex,afterwhichthesoftwareautomatically detectedtheendocardialborderandcreateda3D LVcast (Figure1).

Three-dimensionalspeckle-tracking echocardiography-derivedleftventricular volumetricmeasurements

3D-STE was used to measure LV end-diastolic volume (LVEDV),LVend-systolicvolume(LVESV), LVEFandLVmass basedontheabove-mentionedLVcast.

Three-dimensionalspeckle-tracking

echocardiography-derivedleftventricularstrain assessments

3D-STE strain measurements were performed on the LV cast using the 16-segment LV model.¹⁰ In each segment, threeunidirectionalstrainparameterswereassessed:radial (RS) (thickening and thinning of the segment), longitudinal (LS) (lengtheningand shortening of the segment)and

circumferential (CS) (widening and narrowing of the segment). Based on these strain parameters, the software calculated thefollowing complexstrains: area(AS) (com- binationofLSandCS)and3D(3DS)(combinationofRS,LS andCS).

Statisticalanalysis

All data arereportedas mean± standard deviation. Sig- niﬁcance wasestablished for p valueslessthan 0.05.The Shapiro-Wilks test was used to check for normal distribution. Levene’s test for equality of variances was used totest homogeneity of variance. Fornormallydistributed datasets,thetwo-tailedStudent’sttestwasusedforcom- parisons, however if the dataset did not follow a normal distribution,theMann-Whitney-Wilcoxontestwasused.For categorical variables, Fisher’s exact test was performed.

To establishsigniﬁcant relationshipsbetweenindependent variables, Pearson’s correlation coefﬁcients were calculated.ThestatisticalanalysiswasperformedusingRStudio (RStudio Team, RStudio: Integrated Development for R.

RStudio, Inc., Boston, MA, 2015). Forofﬂine data extrac- tionandanalysis,acommercialsoftwarepackagewasused (MATLAB8.6,TheMathWorksInc.,Natick,MA,2015).

Table1 Demographic,clinical andtwo-dimensional echocardiographic characteristicsofpatients with acromegaly andof controls.

Controls(n=34) Acromegalicpatients(n=25) p

Riskfactors

Age,years 52.7±4.9 57.2±13.6 0.07

Malegender,% 15(44) 7(28) 0.27

BSA,m² 1.87±0.23 2.05±0.29 0.01

Hypertension,% 0(0) 15(60) <0.0001

Hypercholesterolemia,% 0(0) 12(48) <0.0001

Diabetes,% 0(0) 5(20) 0.01

Hypophysectomy,% 0(0) 9(36) 0.0002

2Dechocardiography

LAdiameter,mm 38.8±4.4 42.2±6.1 0.02

LAdiameter/BSA,mm/m² 20.7±2.6 20.6±3.2 0.9

LAvolume,ml 48.8±16.5 54.1±18.0 0.4

LAvolume/BSA,ml/m² 24.1±8.1 28.5±9.5 0.8

LVEDD,mm 47.7±3.3 51.3±5.3 0.006

LVEDD/BSA,mm/m² 25.8±3.1 25.6±4.2 0.9

LVEDV,ml 107.0±20.3 129.9±28.7 0.002

LVEDV/BSA,ml/m² 58.6±9.8 64.9±16.5 0.1

LVESD,mm 31.6±3.0 31.6±4.7 0.95

LVESD/BSA,mm/m² 17.0±2.6 15.9±2.6 0.2

LVESV,ml 37.7±9.0 41.9±14.7 0.2

LVESV/BSA,ml/m² 19.1±6.3 21.3±6.8 0.3

IVS,mm 9.4±1.3 10.3±1.6 0.02

LVposteriorwall,mm 9.6±1.6 10.8±1.8 0.007

E,cm/s 71.5±18.9 65.3±14.0 0.3

A,cm/s 70.3±18.0 79.3±16.1 0.05

E/A 1.06±0.31 0.85±0.21 0.004

LVEF,% 64.5±3.6 67.6±7.2 0.1

2D:two-dimensional;A:latetransmitralﬂowvelocity;BSA:bodysurfacearea;E:earlytransmitralﬂowvelocity;IVS:interventricular septalthickness;LA:leftatrial;LV:leftventricular;LVEDD:leftventricularend-diastolicdiameter;LVEDV:leftventricularend-diastolic volume;LVEF:leftventricularejectionfraction;LVESD:leftventricularend-systolicdiameter;LVESV:leftventricularend-systolicvolume.

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Results

Clinicalanddemographiccharacteristicsof patientswithacromegaly

Signiﬁcantdifferenceswereidentiﬁedbetweenacromegalic patients andhealthy controlsregarding the prevalenceof hypertension(p<0.0001),hypercholesterolemia (p<0.0001) anddiabetes(p=0.01)(Table1).

Laboratoryﬁndingsofpatientswithacromegaly The active acromegaly subgroup consisted of 14 patients (meanage:58.6±14.6years,ﬁvemales).Theirmeanserum HGHlevelwas5.5±3.9ng/ml,IGF-1levelwas502.3±366.0 ng/ml and IGF-1 index (IGF-1 level/upper limit of normal)was2.0±1.1.Theinactiveacromegalygroupincluded 11 patients (mean age: 54.0±12.9, 2 males). Their mean serum HGH level was 4.5±8.1 ng/ml, IGF-1 level was 216.9±129.0ng/mlandIGF-1indexwas0.9±0.6.

Two-dimensionalechocardiographicdata

Significantdifferenceswereseen inLAdiameter(p=0.02), LV end-diastolic diameter (LVEDD) (p=0.006) and volume (LVEDV) (p=0.002), interventricular septal thickness (p=0.02),andLVposteriorwallthickness(p=0.007)between theacromegalic groupand healthycontrols. Body surface area(BSA)wasalsosignificantlydifferentbetweencontrols andacromegalicpatients(p=0.01).Furthermore,latetrans- mitralflowvelocityA(p=0.05)andE/Aratio(p=0.004)also differedsignificantlybetweenthetwogroups(Table1).

Three-dimensionalspeckle-tracking echocardiography-derivedleftventricular volumetricparameters

3D-STE-derived LVEDV (p=0.0003) and LVESV (p=0.005) proved to be significantly different between all the acromegalic patients and controls. LVEDV (p=0.006) and LVEF (p=0.02) differed significantly between the active acromegaly subgroup and controls, while LVEDV (p=0.01) and LVESV (p=0.01) were significantly different between the inactivedisease subgroup andcontrols. LVEF (p=0.02) wassignificantly higherin activethan in inactive disease (Tables2and3).

Three-dimensionalspeckle-tracking

echocardiography-derivedleftventricularstrain parameters

GlobalandmeansegmentalRS(p=0.01andp=0.009,respectively) were significantly higher in acromegalic patients compared tocontrols. Among regional strain parameters, basal and apical RS (p=0.04 and p=0.0004, respectively) were significantlydifferent between acromegalicpatients andcontrols.Patientswithactivediseasehadsignificantly higherglobalandmeansegmentalRS(p=0.03andp=0.03, respectively)comparedtocontrols;in addition,basal and

apicalRS (p=0.04and p=0.002,respectively)andbasal CS (p=0.01)weresignificantlyhighercomparedtocontrols.In patients with inactive disease, no significant differences weredetectedinLVstrainparameterscomparedtothecon- trolgroup.Betweenactiveandinactivediseasegroups,only basal CS (p=0.02) was found to be significantly different (Tables2and3).

Correlationbetweenhormonelevels andthree-dimensionalspeckle-tracking echocardiography-derivedleftventricular volumetricandstrainparameters

In the overall acromegaly group, there was a significant negative correlation between HGH levels and apical 3DS (r=-0.40,p=0.05). Nosignificant correlation wasdetected between any hormone level and LV strains in the active disease group. In the inactive disease group, IGF-1 index correlated significantly with midventricular RS (r=0.60, p=0.05), global and mean segmental RS (r=0.66, p=0.03 andr=0.66, p=0.03,respectively) and global 3DS (r=0.61, p=0.05). Furthermore, there was a significant correlation between mean segmental RS and IGF-1 levels (r=0.61, p=0.05)inthisgroup.

Discussion

Acromegalyisa severechronic hormonaldiseasethatcan affectalmostanyorgansystemthroughelevatedHGHand IGF-1 levels. These effects are especially marked in the cardiovascularsystem,resultinginnumerouscardiovascular comorbidities,themostcommonofwhichishypertension.

Although the pathophysiology is not fully understood, it is hypothesised that circulatory volume increases due to sodium retention and consequent plasma expansion.^11---13 Furthermore,acromegaly is associatedwithcardiomyopa- thy, resulting in severe heart failure in terminal stages.

In the early stages of acromegaly, LV hypertrophy devel- ops due to exposure to elevated serum HGH levels. As acromegaliccardiomyopathydevelops,Ca²⁺hypersensitivity enhances myocardial contractility, resulting in a hyper- kinetic syndrome. As it progresses, LV hypertrophy may becomesufﬁcientlyseveretoimpairLVdiastolicﬁlling.In theterminalstages,bothsystolicanddiastolicfunctionmay decrease due to extracellular collagen deposition.^14---17 In addition,valvularregurgitationand arrhythmiasaremore commonamongacromegalicpatients.^18,19

Inthepresentstudy,3D-STEwasusedtoassessglobaland regionalLVstrainparametersinacromegalicpatients.Strain imaging using 3D-STE has been validated in comparisons with two-dimensional speckle-tracking echocardiography (2D-STE),cardiac magnetic resonance imaging and tissue Dopplerimaging.6,10,20---22Ithasbeenreportedthat3D-STE- derivedLVstrainvaluesaresomewhatlowerthanthosefrom 2D-STE.⁶ Notable advantages of this methodcompared to othermodalitiesareitsnon-invasivenature,angleindepen- dence,possibilityof3Dimagingandlowercost.¹⁰

Tothebestoftheauthors’knowledge,therehavebeen no3D-STEstudiesonLV strainparametersin the acrome- galicpopulation.Therehasbeenonlyonestudywhichused 2D-STE to assess global LV longitudinal strain in patients

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Table2 Comparisonofthree-dimensionalspeckle-trackingechocardiography-derivedglobalandmeansegmentalleftventric- ularpeakstrainparametersbetweenacromegalicpatientsandcontrols.

Controls(n=34) Acromegalicpatients(n=25) Activedisease(n=14) Inactivedisease(n=11) 3D-STE-derivedvolumetricparameters

LVEDV,ml 80.5±20.2 107.6±28.9â 108.5±34.6â 101.1±23.3â

LVESV,ml 34.9±10.6 45.4±14.9^a 43.7±17.7 45.3±12.7^a

LVEF,% 56.7±7.1 58.1±6.1 60.2±5.8^a,^b 55.6±5.8

Globalstrains

Radial,% 25.2±10.8 33.2±13.4^a 35.5±14.4^a 29.7±11.3

Circumferential,% -26.7±6.1 -28.1±4.5 -29.3±4.1 -27.0±4.9

Longitudinal,% -16.0±2.7 -15.8±3.4 -15.5±3.1 -16.1±3.9

3D,% 27.6±10.7 31.3±11.8 32.5±13.8 29.1±8.3

Area,% -39.3±5.8 -39.9±5.2 -40.8±4.7 -39.3±6.0

Meansegmentalstrains

Radial,% 28.2±10.0 36.0±12.1^a 37.9±13.3^a 33.1±9.9

CS,% -28.1±5.9 -29.1±4.3 -30.3±4.1 -28.2±4.4

LS,% -16.9±2.6 -17.0±3.4 -16.7±3.0 -17.5±4.0

3DS,% 30.2±9.8 33.7±10.8 34.6±12.5 31.6±7.6

AS,% -40.4±5.6 -41.2±5.3 -42.1±4.7 -40.6±6.1

ap<0.05vs.controls.

b p<0.05vs.inactivedisease.

3D:three-dimensional;3D-STE:three-dimensionalspeckle-trackingechocardiography;3DS:three-dimensionalstrain;AS:areastrain;CS:

circumferentialstrain;LS:longitudinalstrain;LVEDV:end-diastolicvolume,LVESV:end-systolicvolume,LVEF:leftventricularejection fraction;RS:radialstrain.

Table3 Comparison of three-dimensional speckle-tracking echocardiography-derived regional left ventricular peak strain parametersbetweenacromegalicpatientsandcontrols.

Controls(n=34) Acromegalicpatients(n=25) Activedisease(n=14) Inactivedisease(n=11)

RSbasal,% 34.3±14.8 44.6±19.2^a 46.9±20.7^a 40.2±16.8

RSmid,% 29.6±12.1 34.6±12.8 35.8±14.2 32.1±10.1

RSapex,% 16.9±8.3 25.6±10.1^a 27.9±10.6^a 23.9±10.4

CSbasal,% -26.1±5.8 -28.9±4.9 -30.2±4.8^a,^b -26.7±4.1

CSmid,% -28.4±7.4 -28.5±5.0 -29.3±5.1 -27.8±5.2

CSapex,% -30.6±12.6 -30.6±10.0 -31.7±9.2 -31.1±9.7

LSbasal,% -20.8±5.0 -19.1±5.5 -18.3±6.1 -19.3±4.4

LSmid%) -13.6±4.1 -14.7±3.6 -15.0±2.9 -15.0±4.7

LSapex,% -16.0±5.5 -17.3±7.7 -16.9±8.7 -18.4±6.4

3DSbasal,% 37.1±13.9 44.3±17.4 45.9±19.5 40.7±13.9

3DSmid,% 30.7±11.9 30.3±12.5 31.2±14.2 28.1±9.1

3DSapex,% 19.2±9.3 21.8±10.8 23.0±10.9 21.5±11.4

ASbasal,% -40.6±6.8 -41.6±7.1 -42.0±7.8 -40.0±5.5

ASmid,% -38.8±7.5 -39.0±6.2 -40.4±5.4 -38.3±7.5

ASapex,% -42.7±14.4 -43.8±12.8 -44.6±12.2 -45.0±12.5

ap<0.05vs.controls.

b p<0.05vs.inactivedisease.

3DS:three-dimensionalstrain;AS:areastrain;CS:circumferentialstrain;LS:longitudinalstrain;RS:radialstrain.

withactiveacromegaly,byVolschanetal.,whoreportedno signiﬁcantdifferencesinglobalLV-LScomparedtohealthy controls.²³Ourgrouphaspreviouslyreportedincreasedaor- ticstiffness in acromegaly aswell asreduced LV rotation andtwistinboth activeandinactive acromegaly.It could behypothesizedthatthesechangesaretheconsequences ofextracellularcollagendeposition.^24,25

Results of the 2D echocardiography study in our population showed that in patients with acromegaly, the LV

wasdilated, LVwalls weresignificantly thicker andthere was impaired LV diastolic function without LV systolic dysfunction.Ofthe3D-STE-derivedLVvolumetricparame- ters,LVEDVwassignificantlyincreasedregardlessofdisease activity.Inpatientswithactiveacromegaly,LVEFwashigher comparedtothecontrolgroup,andwassignificantlyhigher than in the inactive acromegaly group. Global and mean segmentalLV-RSweresignificantlyhigherincasesofactive disease compared toboth the healthy controls and those

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withinactivedisease.ItshouldbenotedthatLVstrainval- ueswerenormalinpatientswithinactiveacromegaly.Based ontheseﬁndings,itcouldbehypothesizedthat enhanced regionalstrainmaybeacompensatorymechanismoffsetting theimpairedLVrotationandtwistdemonstratedrecently.²⁵ Our results suggest that LV deformation differences are reversiblewithpropertreatment,butnotLVdilation.Fur- therinvestigationsarewarrantedtoassesswhyLVrotation andtwist areimpaired but LV wallcontractility is not. In addition, LV-RS appears to compensate for the loss of LV twist.

Limitations

There areseveral limitations affecting the present study.

Sinceacromegalyisararedisease,thestudypopulationis relativelysmall.ThedurationofexposuretohighserumHGH andIGF-1concentrationswasnottakenintoaccountinthe analysis,andthepossibleeffectsofdrugsusedinthetreat- mentofacromegalywerenotexamined.3D-STEasanovel modalitysuffersfromseveral limitingtechnicalfactors:it haslowerspatialandtemporalresolutionthan2D-STE,and thefull-volumedatasetrequiressixidenticalRRintervals, which can resultin so-called stitchingnoise.²⁶ It has also beenreportedthatLVstrainparametersshowsomevendor dependency.²⁷ Finally,thegreaterproportionofwomenin thecontrolgroupcouldpartiallyexplaindifferencesinheart dimensionsbetweenthegroups.

Conclusion

The presented clinical, demographic, therapeutic and echocardiographic features demonstrate that active acromegalyisassociatedwithenhancedLV-RSascompared tohealthycontrolsandthosewithinactiveacromegaly.

Ethical standards

Theauthorsassertthatall procedurescontributingtothis work comply with the ethical standards of the relevant nationalguidelinesonhumanexperimentationandwiththe 1975Helsinki Declaration,revised in2008,and havebeen approvedbytheinstitutionalreviewboardoftheUniversity ofSzeged.

Author contributions

Árpád Kormányos --- study design, writing manuscript, patientmanagement,performing3D-STEexaminations.

PéterDomsik---patientmanagement,performing3D-STE examinations.

AnitaKalapos---patientmanagement,performing3D-STE examinations.

Nándor Gyenes--- patientmanagement,performing3D- STEexaminations.

ZsuzsannaValkusz---supervision.

CsabaLengyel---supervision.

TamásForster---supervision.

AttilaNemes---studydesign,writingmanuscript.

Conﬂicts of interest

Theauthorshavenoconﬂictsofinteresttodeclare.

Acknowledgments

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

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