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ORIGINAL ARTICLE

EvaluationofcardiacfunctionsofcirrhoticchildrenusingserumbrainnatriureticpeptideandtissueDopplerimaging

Aya M Fattouh, Mortada H El-Shabrawi, Enas H Mahmoud1, Wafaa O Ahmed

DepartmentsofPediatricsandChemicalPatholog!"Cairo#niversit!"Cario"Eg!pt

ABSTRAT

Background : Cirrhotic

cardiomyopathy

(CCM)

is

described

as

the

presence

of

cardiac

dysfunction

in

cirrhotic

patients.

In

children

with

chronic

liver

disease,

CCM

has

been

very

rarely

investigated.

TheAim

ofthe

: Is

to

evaluate

the

cardiac

function

of

cirrhotic

children

to

identify

those

with

CCM.

Study

Patientsand: Fifty-twocirrhoticpatientsand53ageandsexmatchedcontrolswereassessedusing

Methods serum

brain-typenatriureticpeptide(BNP),conventionalechocardiography,andtissue

Dopplerimaging.

Results : Patientsmeanageswere7.664.16years(vs.6.883.04yearsforthecontrols).Thestudy

included

27

males

and

25

females

(28

and

25

respectively

for

the

controls).

Patients

hadlargerleftatriumandrightventricle(RV)(Pvalue0.05)andincreasedLVposteriorwall

thicknessthancontrols(Pvalue0.04).Theyhadhigherlateatrialdiastolicfillingvelocity

(A)oftricuspidvalve(TV)inflow

(0.59

.0.50.1m/s,P


2/8

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1234AnnalsofPediatricCardiolog!5Publishedb!6olters7lu$er)'ed%no$

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114.121.12.!"#

$attouh,etal.16N+andtissue*opplerima"in"incirrhoticchildren

s!stemicvascularresistance"increasedcardiacoutput"

andabnormalm!ocardialcontractilefunctionare

thecharacteristicfeaturesandli%el!toappearas

conse8uencesofcirrhosis&Thefunctionalandstructural

changesofthem!ocardiumhavebeenreferredas

cirrhoticcardiom!opath!9CC':"aslo$progressionof

m!ocardiald!sfunctionassociated$ithcirrhosis&;or altered diastolic rela?ation $ith

electroph!siological abnormalities in the absence

ofother%no$ncardiacdisease&Diagnosticcriteria

included/*!stolicd!sfunction9bluntedincreasein

cardiacoutput$ithe?ercise"volumechallengeor

pharmacologicalstimuliandrestinge@ectionfraction

;E


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114.121.12.!"#

$attouh,

et

al.1

6N+

and

tissue

*oppler

ima"in"

in

cirrhotic

children

Trans)mitral andtrans)tricuspidflo$s$ereobtained

$ithpulsed$aveDopplerattheleaflettipsJearl!

diastolicinflo$velocit!9E:"velocit!duringactiveatrial

contraction9A:"EtoA$ave9E>A:ratio"andDt$ere

measured&

TDI$asobtainedfromthefourchambersapicalvie$"

andtissuevelocities$erecalculatedsingpulsedtissue

velocit!

indices"

the

sample

volumes

$ere

placed

inthelateralsidesofthemitralandtricuspidannuluses

andthebaseoftheinterventricularseptum&Thepea%

s!stolicandearl!andlatediastolicvelocities9EKand

AK"respectivel!:atthesepoints$eremeasured"andthe

E>EKratio$ascalculated&Theisovolumicrela?ationtime

9IRT:andisovolumiccontractiontime9ICT:$ereboth

measuredforbothLandRlateral$alls&

Calculationofglobalm!ocardialperformanceinde?

9'PIinde?:$asperformedb!pulsedtissuevelocit!

imaging&ortissueDoppler"allintervalmeasurements

$ereperformed$ithinonecardiacc!cle&The'PIinde?

$as

calculated

ab>b

$here

a

is

the

time

interval

fromthe

end

of

AK

$ave

to

the

onset

of

EK

$ave

and

b thetime

fromtheonsettotheendofthe*K$ave&

Toreducetheeffectofrespirationontissuevelocities

andasbreathholding$asnotapplicablein!oung

children"threecardiacc!cles$ere"recorded"andthe

averagevelocit!$ascalculated&Toreduceintraobserver

variabilit!threedifferentmeasurementsforeachtissue

Dopplerinde?$asdoneandtheaverage$asta%en&

+aboratory in)esti*ations

Routinelaborator!forthecasesincluded/Complete

blood

count"

prothrombin

time"

and

prothrombinconcentration 9PT and PC: and the International

Normali=edRatio9INR:"biochemicalliverfunctiontests/

Alanineaminotransferase"aspartateaminotransferase

9A*T:"al%alinephosphatase9ALP:"totalanddirect

bilirubin"andserumalbumin&

Measurement of brain natriureti% &e&tide le)el

Floodsample$as$ithdra$nfromeachpatientand

collectedinaplaintube"lefttoclotfor3)23min&at

roomtemperaturebeforecentrifugationfor3minat

thespeedof2333)333rounds>min&Theserum$as

separatedstoredat23MCtillthetimeofassa!forserum

FNP&

FNP

measurement

$as

performed

using

8uantitativeen=!melin%edimmunosorbentassa!using%itsupplied

b!67EA'ed*uppliesCorp9China:&

Statisti%al

methods

The*P**,&3for$indo$s9*P**Inc&"Chicago"IL"#*A:

$asusedfordatamanagementandanal!sisandthe

'icrosoftpo$erpointforcharts&Parametric8uantitative

data$erepresentedasameanstandarddeviation&

orcomparisonoftthreegroupsKmeans"one)$a!

anal!sisofvariance$asusedfollo$edb!posthoc

test&Nonparametric8uantitativedata$eree?pressed

as

median

9range:"

7rus%all6allis

and

'ann6hitne!

tests$ereusedforcomparisonofmedians&Correlation

bet$een8uantitativevariables$asdoneappl!ing

Pearsonran%edcorrelationtest9forparametricdata:and

*pearmenran%edcorrelationtest9fornon)parametric

data:&ualitativedata$ase?pressedasfre8uenc!and

percentage&

The

diagnostic

performance

of

serum

FNP$as

evaluated

using

the

receiver

operating

characteristics

9ROC:

curve"

in

$hich

sensitivit!

$as

plotted

on

the

)a?is

and33)specificit!ontheQ)a?is&Pvalue$asconsidered

significantat3&3,&

RES$+TS

Thebaselinecharacteristicsoftheincludedpatientsare

sho$ninTable&

Thecasesandcontrols$ereageandse?matched&

PatientKs mean ages $ere -&44 H&4 !ears 9vs&

4&..&3H!earsforthecontrols"P3&:&Thestud!

included

2-

males

and

2,

females

versus

2.

males

and

2,femalesforthecontrols&ThePvaluebet$eenthe

meanageofcasesandcontrols$as3&$hilebet$een

thenumbersofmalepatients$as3&H"andthenumber

offemalepatients$as3&&

Thepatientshadsignificantl!dilatedLA"R"and

pulmonar!arter!9PA:diametersandincreasedL

posterior$allthic%nessthancontrols&The!alsohad

significantl!lo$erE>A9ofbothmitralandtricuspid

inflo$:andhigherA$aveofthetricuspidinflo$as

sho$ninTable2&

TDIsho$edthatpatientshadsignificantl!longerIRT

9P

value

3&33.:

and

shorter

ICT

of

the

L

9P

value

3&3:&

The!alsohadhigherlatediastolicpea%m!ocardial

velocit!9AK:ands!stolicvelocit!9*K:oftheR9P

valueof3&333and3&3"respectivel!:andshorter

ICToftheR9Pvalue3&32:&Thepatientsalsohad

Table1:Baselinecharacteristicsofpatients

included in the study (original)

Categoricalvariables Frequency Percentage

SexMales

27

51.9Females 25 48.1

UnderlyingliverpathologyChronichepatitis

10

19.2Extrahepaticbiliaryatresia 6 11.5Autoimmunehepatitis

5

9.5Wilsonsdisease

1

1.9-1antitrypsindeficiency 1 1.9Cryptogeniccirrhosis 29 55.8

DiseasestateCompensated 34 65.4Decompensated

18

34.6Continuousvariables

MeanSDAge(years)

7.664.16

SD:Standarddeviation

AnnalsofPediatricCardiolog!234ol+Issue

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4/8

$attouh,etal.16N+andtissue*opplerima"in"incirrhoticchildren

higherseptalAKvelocit!9Pvalue3&333:"lo$erseptal

EKvelocit!9Pvalue3&3H:andhigherseptal*Kvelocit!

9Pvalue3&33:thancontrols&'PIinde?ofbothLand

R$assignificantl!higherincasesthancontrols9Pvalue

3&333and3&333:denotingglobalcardiacd!sfunction&

Tablesho$sthecomparisonbet$eencasesandcontrols

regardingthetissueDopplerindices&

Patientshadasignificantl!higherlevelofFNPassho$n

inigure&ThemedianlevelofFNPinpatients$as

,&2,

ng>L

9range

)4.:

versus

&-,

ng>L

93)3:

in

controls9Pvalue3&3H:&igure2sho$edtheROCcurve

forFNPcut)offamongcasesandcontrols&

There$asnosignificantcorrelationbet$eenFNPlevel

andtheclinicalandlaborator!findingsofourpatients"

assho$ninTableH"andthere$asnosignificant

correlationalsobet$eenFNPlevelandetiolog!ofliver

cirrhosis&FNPlevels$eresignificantl!correlated$ith

theE$avevelocit!oftheTinflo$assho$ninTable,

and$ithE>$aveofTassho$ninTable4&

Thepatients$ithdecompensatedlivercirrhosishad

significantl!

lo$er

s!stolic

blood

pressure

and

higherheartrate9Pvalue3&32and3&3"respectivel!:&Patients

$ithdecompensatedliverdiseasehadsignificantl!larger

Rdiameter"increasedI*thic%ness"andshorterDt

ofthetricuspidinflo$assho$ninTable-&TDIresults

sho$ednosignificantdifferencebet$eenbothgroups

ofpatients;Table.


5/8

Table3:ComparisonbetweentissueDoppler

indices forpatientsandcontrolsParameter MeanSD P

Patients(n=52)Controls(n=53)

LV(cm/s) 7.7(2.3) 6.9(1.9) 0.08(cm/s) 16.94(3.98) 18.19(3.31) 0.16(cm/s) 9.4(2.4) 8.9(2.3) 0.26E/ 6.68(2.14) 6.01(1.39) 0.07IVRT(ms) 45.5(11.1) 40.5(7.7) 0.008**IVCT(ms) 41.7(8.7) 45.9(10.8) 0.03**MPIindex 0.36(0.09) 0.3(0.04) 0.001

RV(cm/s) 11.8(3.6) 9.5(2.7) 0.0003**(cm/s) 17.67(3.9) 17.65(3.5) 0.76(cm/s) 14.5(2.7) 13.2(2.9) 0.01*E/ 4.53(1.7) 4.28(1.25) 0.29IVRT(ms) 40.4(9.6) 37.4(7.9) 0.08IVCT(ms) 42.2(9.4) 46.8(10.2) 0.02*MPIindex 0.32(0.06) 0.3(0.034) 0.01*

Septum(cm/s) 7.38(2.1) 5.9(1.3) 0.0001*(cm/s) 13.4(2.5) 14.4(2.6) 0.04*(cm/s) 8.7(2.5) 7.4(1.3) 0.001**

LV:Leftventricle,RV:Rightventricle,IVRT:Isovolumetricrelaxationtime,IVCT:Isovolumetriccontractiontime,MPI:Myocardialperformanceindex,:Systolicmyocardialvelocity,and:Earlyandlatediastolicmyocardialvelocities,SD:Standarddeviation,PvalueconsideredsignificantifAratioofboth

mitral

and

Ts

inflo$

$ere

significantl!

lo$er

in

casesthancontrolsandtheIRT$assignificantl!longer&

Theunderl!ingmechanismofdiastolicd!sfunctionin

cirrhosisisli%el!duetotheincreasedm!ocardial$all

stiffnesscausedb!m!ocardialh!pertroph!"fibrosisand

subendothelialedema"andsubse8uentl!resultingin

Table5:CorrelationbetweenBNPvaluesandecho

parameters(M-modedimensionsandDopplerindices)ofpatientsParameter r P

AO

(mm)

0.036

0.8LA(mm)

0.072

0.6RV(mm)

0.074

0.6PA(mm)

0.032

0.8IVS(mm)

0.082

0.5PW(mm) 0.141 0.3EDD(mm)

0.150

0.3ESD(mm) 0.127 0.4EFpercentage

0.062

0.6FSpercentage 0.120 0.4MV

E(m/s) 0.075 0.6A(m/s)

0.583

0.3E/A 0.144 0.1DT(ms)

0.213

0.2TV

E(m/s)

0.398

0.004*A(m/s)

0.046

0.8E/A

0.169

0.2DT(ms) 0.124 0.4

Pvalueconsideredsignificantif


6/8

AO

(mm) 20.5(4.8) 19.3(4.1) 0.38LA(mm) 24.7(4.11) 25.2(6.4) 0.8RV(mm) 14.7(3.8) 12.8(2.9) 0.05*PA(mm) 18.1(4.5) 16.9(4.2) 0.37PW

(mm) 6.3(1.4) 5.9(1.2) 0.29IVS(mm) 6.1(1.4) 5.3(1.1) 0.04*EDD(mm) 36.1(6.4) 36.9(7.2) 0.65ESD(mm) 21.8(4.9) 22.5(4.6) 0.6EFpercentage 71.5(8.3) 70.9(4.7) 0.8FSpercentage 42(74) 39.6(3.98) 0.2LV

E(m/s) 1.09(0.2) 1.01(0.13) 0.1A(m/s) 0.64(0.13) 0.66(0.2) 0.6E/A 1.7(0.36) 1.6(0.33) 0.2DT(ms) 138.1(45.9) 104.1(57.1) 0.02*

RVE(m/s) 0.75(0.18) 0.76(0.2) 0.89A(m/s) 0.54(0.14) 0.64(0.22) 0.2E/A 1.4(0.28) 1.3(0.32) 0.2DT(ms) 156.3(60.9) 131.3(84.6) 0.2

AO:Aorta,LA:Leftatrium,PA:Pulmonaryartery,RV:Rightventricle,IVS:Interventricularseptum,LVPW:Leftventricularposteriorwall,EF:Ejectionfraction,FS:Fractionalshortening,MV:Mitralvalve,E:Ewavevelocity,A:Awavevelocity,E/A:E/Aratio,Dt:Decelerationtime,TV:Tricuspidvalve,SD:Standarddeviation,PW:Pulsedwave,EDD:Enddiastolicdimension,ESD:Endsystolicdimensions,Pvalueconsideredsignificantif


7/8

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&PUll

A"

C=ifra

A"

itUlis

V"

Papp

'"

Paragh

G"

*=abW

V&Pathoph!siological and clinical approach tocirrhoticcardiom!opath!&XGastrointestinLiverDis23HJ2/3)3&

2&'Yller*"(enri%senX(&Cirrhoticcardiom!opath!&

X(epatol233J,/-+)+3&

&

Fai%

*7"

ouad

TR"

Lee

**&

Cirrhotic

cardiom!opath!&

OrphanetXRareDis233-J2/,&

H&

Naschit=

XE"

*lobodin

G"

Le$is

RX"

Vuc%erman

E"eshurun

D&

(eart

diseases

affecting

the

liver

and

liverdiseasesaffectingtheheart&Am(eartX2333JH3/)23&

,&'Yller

*"

(enri%sen

X("

Fendtsen

&

E?trahepatic

complications

to

cirrhosis

and

portal

h!pertension/(aemod!namicandhomeostaticaspects&6orldXGastroenterol

23HJ23/,H++),-&

4&*cardoviAFJAssocia=ioneNa=ionale'ediciCardiologi

OspedalieriJ

*ocietZ

Italiana

di

Cardiologia

PediatricaJ*ocietZ

Italiana

di

Nefrologia

PediatricaJ

*ocietZ

ItalianadellKIpertensioneArteriosaJ*ocietZItalianadiPediatria&Clinical

applications

of

brain

natriuretic

peptide

testing&Ital(eartX*uppl233HJ,/H),4&

-&'eune

C"

ulla

"

'artins

E"

Fergmann

X"

Devau?

X&

F)t!pe

natriuretic

peptide

for

the

diagnostic

andprognostic

assessment

in

cardiolog!&

Its

interest

andperspectives

of

application&

Presse

'ed

233J2/.),&

.&(enri%senX("GYt=eXP"uglsang*"ChristensenE"

Fendtsen

"

'Yller

*&

Increased

circulating

pro)brain

natriureticpeptide9proFNP:andbrainnatriureticpeptide9FNP:inpatients$ithcirrhosis/Relationtocardiovascular

d!sfunction

and

severit!

of

disease&

Gut233J,2/,)-&

+&

amaguchi

("

oshida

X"

amamoto

7"

*a%ata

"

'anoT"A%ehiN"etal&Elevationofplasmabrainnatriuretic

peptide

is

a

hallmar%

of

diastolic

heartfailureindependentofventricularh!pertroph!&XAmCollCardiol233HJH/,,)43&

3&7a=an%ov7"(olland)ischerP"AndersenN("TorpP"

*loth

E"

Aagaard

N7" et al& Resting m!ocardial

d!sfunctionincirrhosis8uantifiedb!tissueDopplerimaging&LiverInt23J/,H)H3&

&GassanovN"Cagla!anE"*emmoN"'assen%eilG"Er&

Cirrhotic

cardiom!opath!/

A

cardiologistKs

perspective&6orldXGastroenterol23HJ23/,H+2).&

2&6ong"*iu*"LiuP"FlendisL'&Frainnatriuretic

peptide/

Is

it

a

predictor

of

cardiom!opath!

in

cirrhosis[Clin

*ci

9Lond:

233J3/42).&

&'eric'"esildagO"u%sel*"*o!lu7"Arslandag'"

DursunI"etal&Tissuedopplerm!ocardialperformanceinde?

in

patients

$ith

heart

failure

and

its

relationship$ithhaemod!namicparameters&IntXCardiovascImaging23HJ3/3,-)4H&

H&

'erli

'"

Calicchia

A"

Ruffa

A"

Pellicori

P"

Riggio

O"

Giusto

'"

et

al&

Cardiac

d!sfunction

in

cirrhosis

is

not

associated

$ith

the

severit!

of

liver

disease&

Eur

X

Intern'ed23J2H/-2)4&

,&

ildi=

R"

ildirim

F"

7arincaoglu

'"

(arputluoglu

'"

(ilmioglu

&

Frain

natriuretic

peptide

and

severit!of disease in non)alcoholic cirrhotic patients&X

Gastroenterol

(epatol

233,J23/,)23&

4&

Padilloa

X"

Pilar

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'ar\a

C"

Xuan

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Tur%

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Gastroenterol233J2/.)4&


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