Jurnal Peds - Dokter Tika Translated

8/19/2019 Jurnal Peds - Dokter Tika Translated

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Evaluation of cardiac functions of cirrhotic children using

serum brain natriuretic peptide and tissue Doppler imaging

ABSTRACT

Background: Cirrhotic cardiomyopathy (CCM) is described

as the presence of cardiac dysfunction

in cirrhotic patients. n chi!dren "ith chronic !i#er disease$

CCM has been #ery rare!y

in#estigated.

The Aim of the : s to e#a!uate the cardiac function of

cirrhotic chi!dren to identify those "ith CCM.

Study

%atients and : &ifty't"o cirrhotic patients and age and

se* matched contro!s "ere assessed using

Methods


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serum brain'type natriuretic peptide (B+%)$ con#entiona!

echocardiography$ and tissue

,opp!er imaging.

Resu!ts : %atients- mean ages "ere .// 0 1.2/ years

(#s. /.33 0 .41 years for the contro!s). The study

inc!uded 5 ma!es and 5 fema!es (53 and 5 respecti#e!y

for the contro!s). %atients had

!arger !eft atrium and right #entric!e (R6) (% #a!ue 4.4) and

increased 76 posterior "a!!

thickness than contro!s (% #a!ue 4.41). They had higher !ate atria!

diasto!ic 8!!ing #e!ocity

(A) of tricuspid #a!#e (T6) in9o" (4. 0 4.2 #s. 4. 0 4.2 m;s$ %

< 4.442) and !o"er ratios

bet"een the ear!y diasto!ic 8!!ing #e!ocity (=) and A "a#e

#e!ocity (=;A) of both mitra!

#a!#e and T6 in9o" (2. 0 4. #s. 2.3 0 4.1 and 2.

0 4. #s. 2. 0 4.$ % < 4.44 and


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4.4443$ respecti#e!y). %atients had signi8cant!y !onger

iso#o!umic re!a*ation time of 76

(1. 0 22.2 #s. 14. 0 . ms % 4.443)$ higher !ate

diasto!ic peak myocardia! #e!ocity (A>)

(22.3 0 ./ #s. . 0 5. ms$ % 4.444) and systo!ic #e!ocity (S>)

of the R6 (21. 0 5. #s. 2.5

0 5.$ % 4.42) and signi8cant!y higher myocardia! performance

inde* of both 76 and R6

(% 4.442 and 4.42). B+% !e#e!s "ere signi8cant!y higher in

cases than contro!s (.5 ng;!

#s. . ng;!$ % < 4.41) and "as corre!ated "ith the = "a#e

#e!ocity of the T6 (r 4.441) and

the =;=> ratio of the R6 (r 4.442). +one of the c!inica! or

!aboratory data "ere corre!ated

"ith the B+% !e#e!.

Conc!usion : Cirrhotic chi!dren ha#e cardiac dysfunction

main!y in the form of diasto!ic dysfunction.

There is a need that CCM be more accurate!y described in

chi!dren.


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?ey"ords : Brain'type natriuretic peptide$ cirrhotic

cardiomyopathy$ !i#er cirrhosis$ tissue ,opp!er imaging

Cirrhosis is associated with an increased risk for the

development of cardiovascular diseases. Decreased systemic

vascular resistance, increased cardiac output,

and abnormal myocardial contractile function are

the characteristic features and likely to appear as

consequences of cirrhosis. The functional and structural

changes of the myocardium have been referred as

cirrhotic cardiomyopathy (CCM, a slow progression of

myocardial dysfunction associated with cirrhosis.!"# $t is

de%ned as cardiac dysfunction in patients with cirrhosis

characteri&ed by impaired contractile responsiveness

to stressand'or altered diastolic relaation with

electrophysiological abnormalities in the absence


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of other known cardiac disease. Diagnostic criteria

included) *ystolic dysfunction (blunted increase in

cardiac output with eercise, volume challenge or

pharmacological stimuli and resting e+ection fraction

!-# //0, diastolic dysfunction ('1 ratio ".2,

prolonged deceleration time (Dt 3422 ms, prolonged

isovolumetric relaation time, 352 ms, and other

supportive criteria (electrophysiological abnormalities,

abnormal chronotropic response, electromechanical

uncoupling or dyssynchrony, prolonged 67T interval,

enlarged left atrium (81, increased myocardial mass,

increased brain7type natriuretic peptide (9:; and pro7

9:;, and increased troponin $.!4#

:ot all of the above are necessary to make a diagnosis.!


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fully understood, early detection of this condition is

perhaps important.!=# This cardiac dysfunction may a>ect

the prognosis of the patients and aggravate the course

during invasive procedures such as surgery, insertion

of a trans+ugular intrahepatic portosystemic shunt, and

liver transplantation.!/#

9:; has been recently used in the di>erential diagnosis

and follow7up of patients with heart failure. $t is a

neurohormone released by the ventricular myocytes and

plays a key role in volume homeostasis.!?#

;lasma 9:; level is a sensitive indicator of ventricular

dysfunction both in symptomatic and asymptomatic

patients and its plasma concentration increases with volume

and pressure overload in patients with heart failure.!@#

*everal studies have shown increased plasma levels of

9:; in some patients with cirrhosis, and these %ndings


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may suggest cardiac dysfunction.!5# $n addition to the

left ventricular (8A systolic dysfunction, plasma 9:;

levels have been suggested to be signi%cantly associated

with diastolic stage (including newer echocardiographic

parameters as tissue Doppler imaging (TD$ and color

M7mode propagation velocity and right ventricle (BA

functions as well.!#

e sought to determine whether children with cirrhosis

and without heart failure have compromised myocardial

function detectable in the resting stage. Thus, the

ob+ective of our study was to evaluate the serum level

of 9:; and its relationship with clinical, laboratory,

echocardiographic, and TD$ functions in cirrhotic

children in an attempt to diagnose pediatric CCM.

;1T$:T* 1:D MTEFD*


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The design was a case control observational study,

including /4 consecutive ambulatory and hospitali&ed

patients with cirrhosis concomitantly with /< controls

matched for age and se. These controls were volunteers,

friends, or neighbors of the patients or workers or nurses

in the hospital.

They were matched prospectively for age, gender,

and 9M$. -ull physical eamination including cardiac

eamination and blood pressure measurement, as well as

echocardiography was performed before recruiting them

to ensure that they do not have an underlying cardiac

problem. The diagnosis of cirrhosis was established

through a combination of biochemical, clinical, liver

biopsy, and ultrasonographic %ndings. ;atients with

congenital and other acquired heart diseases were

ecluded from the study. $nformed consent was obtained


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from all included patients and controls. The study was

approved by the $nstitutional thical Committee.

Clinical evaluation

Fn the day of the study, heart rate and blood pressure

were measured. ;atients provided a detailed clinical

history and had a thorough clinical eamination and

blood tests (including hematologic and biochemical

pro%le. ;atients were classi%ed as with compensated

or decompensated cirrhosis based on the absence or

presence of ascites, esophageal varices and hepatic

encephalopathy. Therapies administered in the last

weeks were recorded. 1ll the controls were sub+ected to

detailed history taking and full clinical eamination with

thorough cardiac eamination.

chocardiography

chocardiography was performed for all cases and


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controls in the supine, left lateral position using General

lectric (G, Aivid7/ system with probe < or / ME&

(multi7frequency transducer according to the age of

patient, having tissue velocity imaging capabilities.

The electrocardiography cable was connected to the

ultrasound machine to de%ne and to time the cardiac cycle

events. The eamination was performed by a pediatric

cardiologist who had epert in echocardiography

and TD$ in accordance with the recommendations

of the 1merican *ociety of chocardiography.!"2# The

echocardiographer was not blind to patients versus

controls. The eamination consisted of M7mode, two7

dimensional, pulsed7wave, and color Doppler blood How

velocity measurements of the heart valves. 8A fractional

shortening (-* and - were calculated.

Trans7mitral and trans7tricuspid Hows were obtained


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with pulsed wave Doppler at the leaHet tipsI early

diastolic inHow velocity (, velocity during active atrial

contraction(1, to 1 wave ('1 ratio, and Dt were

measured.

TD$ was obtained from the four chambers apical view,

and tissue velocities were calculated. Jsing pulsed tissue

velocity indices, the sample volumes were placed in

the lateral sides of the mitral and tricuspid annuluses

and the base of the interventricular septum. The peak

systolic and early and late diastolic velocities (K and

1K, respectively at these points were measured, and the

'K ratio was calculated. The isovolumic relaation time

($ABT and isovolumic contraction time ($ACT were both

measured for both 8A and BA lateral walls.

Calculation of global myocardial performance inde

(M;$ inde was performed by pulsed tissue velocity


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imaging. -or tissue Doppler, all interval measurements

were performed within one cardiac cycle. The M;$ inde

was calculated aLbL'bL where aL is the time interval from

the end of 1K wave to the onset of K wave and bL the time

from the onset to the end of the *K wave.

To reduce the e>ect of respiration on tissue velocities

and as breath holding was not applicable in young

children, three cardiac cycles were, recorded, and the

average velocity was calculated. To reduce intraobserver

variability three di>erent measurements for each tissue

Doppler inde was done and the average was taken.

8aboratory investigations

Boutine laboratory for the cases included) Complete

blood count, prothrombin time, and prothrombin

concentration (;T and ;C and the $nternational

:ormali&ed Batio ($:B, biochemical liver function tests)


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1lanine aminotransferase, aspartate aminotransferase

(1*T, alkaline phosphatase (18;, total and direct

bilirubin, and serum albumin.

Measurement of brain natriuretic peptide level

9lood sample was withdrawn from each patient and

collected in a plain tube, left to clot for "2742 min. at

room temperature before centrifugation for "2 min at

the speed of 42227


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data were presented as a mean P standard deviation.

-or comparison of t three groupsK means, one7way

analysis of variance was used followed by post hoc

test. :onparametric quantitative data were epressed

as median (range, OruskallQallis and MannQhitney

tests were used for comparison of medians. Correlation

between quantitative variables was done applying

;earson ranked correlation test (for parametric data and

*pearmen ranked correlation test (for non7parametric

data. 6ualitative data was epressed as frequency and

percentage. The diagnostic performance of serum 9:;

was evaluated using the receiver operating characteristics

(BFC curve, in which sensitivity was plotted on the R7ais

and "227speci%city on the S7ais. ; value was considered

signi%cant at 2.2/.


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B*J8T*

The baseline characteristics of the included patients are

shown in Table ".

The cases and controls were age and se matched.

;atientKs mean ages were @.?? P =."? years

(vs.

?.55 P


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signi%cantly lower '1 (of both mitral and tricuspid

inHow and higher 1 wave of the tricuspid inHow as

shown in Table 4.

TD$ showed that patients had signi%cantly longer $ABT

(; value 2.225 and shorter $ACT of the 8A (; value 2.2


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;atients had a signi%cantly higher level of 9:; as shown

in -igure ". The median level of 9:; in patients was

/.4/ ng'8 (range "7"?5 versus


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BA diameter, increased $A* thickness, and shorter Dt

of the tricuspid inHow as shown in Table @. TD$ results

showed no signi%cant di>erence between both groups

of patients !Table 5#. There was no signi%cant di>erence

between the median levels of the 9:; in both groups

(; value 2.=.

D$*CJ**$F:

Most patients with stable liver disease have subtle

myocardial impairment that is not or less apparent on

routine eamination. Eowever, with progression of the

liver disease or under physiological or pharmacological

strain, the cardiac failure becomes manifest.!""# During

the last years several studies have focused their attention

on the presence of speci%c cardiac abnormalities in


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cirrhotic patients.

$n this cross7sectional study, we evaluated the cardiac

functions of /4 cirrhotic children using both conventional

echocardiography and TD$ in addition to serum 9:;

level. e found that our patients had signi%cantly

larger 81, BA, and ;1 diameters and increased 8A;

as reported by other investigatorsK studies.!"2,"4# The

systolic functions of our patients were not a>ected when

assessed by -* and - which were within normal limits.

*ystolic peak velocity of the 8A measured by TD$ was not

reduced which could be attributed to the hyperdynamic

status accompanying cirrhosis. The '1 ratio of both

mitral and TAs inHow were signi%cantly lower in cases

than controls and the $ABT was signi%cantly longer.

The underlying mechanism of diastolic dysfunction in

cirrhosis is likely due to the increased myocardial wall


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sti>ness caused by myocardial hypertrophy, %brosis and

subendothelial edema, and subsequently resulting in

high %lling pressures of the left ventricle and atrium.!""#

Combining TD$ with Doppler indices by using parameters

as 'K allows re%ning the criteria required to detect

patients with diastolic dysfunction especially for those

with hyperdynamic state accompanying liver cirrhosis.

The M;$ which reHects both the globalI systolic and

diastolic, function of the heart!"


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showed no signi%cant di>erence between compensated

and decompensated cirrhotic patientsI a %nding that was

also reported by other investigators.!"ect its level. Fther investigators reported

association between the level of 9:; and pro79:; and

the severity of lever disease.!5,"/,"?#

$n this study, serum 9:; level was correlated with wave

velocity of TA inHow and '1 ratio of BA. Fther studies

had demonstrated correlations with di>erent parameters

as ; thickness,!5,"2,"4# DT, and DD,!"4# as well as $A*.!5#

To the best of our knowledge, no studies had correlated

between 9:; and TD$ in pediatric patients with liver

cirrhosis.


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There is diUculty in applying the current diagnostic

criteria for diagnosing CCM in the pediatric age group.

There is not enough data regarding how much of these

criteria are required for diagnosis. *ystolic functions

are usually preserved till very late in the course, so it

cannot be counted on for early diagnosis. Fur patients

may have had better cardiac reserves that might mask the

manifestations of CCM more than the in adults, especially

those with cardiovascular risk factors. :ot enough data

about the normal range of 9:; in children. These factors

made the application of the diagnostic criteria not so

much convenient for use in children.

8imitations of the study included

8ack of data concerning long7term follow7up and

progression of the patient condition. Fur patients

were at di>erent stages of diuresis and intravascular


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volume status which was another limitation of our

study. 1nother limitation was the inability to perform

blinded echocardiographic eamination to patients

versus controls.

CF:C8J*$F:

Cirrhotic children might have cardiac dysfunction in

the absence of other known cardiac diseaseI that might

be labeled as genuine Vcirrhotic cardiomyopathy.W

Currently, there is no single diagnostic tool that can help

to identify patients with CCM. The use of TD$ o>ers a

better tool for early detection of both diastolic and global

cardiac dysfunction. 9:; is a useful marker of cardiac

dysfunction yet it could not be correlated with speci%c

clinical or laboratory %ndings and still further studies are

required to correlate it with echocardiographic %ndings.


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There is a need that the entity CCM be more accurately

described particularly in children.

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Jurnal Peds - Dokter Tika Translated