J Cardiol 2007 Nov; 50（5）: 299 – 307

Prospective Follow-Up Cardiac
Evaluation of Children With
Kawasaki Disease in Northern India
Using the Japanese Echocardiography Criteria
Kavitha

KOTHUR, MD

SurjitSINGH, MD

YashpaulSHARMA, MD＊1

B. R.

MITTAL, MD＊2

Abstract ─────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────
Objectives. There is no information available on the follow-up of children with Kawasaki disease（KD）
in developing countries. This prospective study was undertaken to evaluate the cardiac abnormalities in acohort of children with KD from a tertiary care centre in Northern India.
Methods. Twenty children with diagnoses of KD and followed-up for at least 3 months in the PediatricRheumatology and Immunology Clinic of the Advanced Pediatric Centre, Post Graduate Institute ofMedical Education and Research（PGIMER）, Chandigarh were evaluated between July 2002 to January
2006. Age of onset of disease ranged from 12 months to 10 years. The male : female ratio was 4 : 1. All
patients had received intravenous immunoglobulin（IVIG）
administration in the acute stage. Chest radiography showed no abnormalities in the 15 patients in whom it was done. Electrocardiographic abnormalities
were seen in 3 patients in the form of T wave inversion in 3, ST segment changes in 2, and prolonged PR
interval in 1 patient which normalized on follow-up. The mean time interval between the diagnosis of KD
and first follow-up echocardiography was 7.9 ± 3.5 months（range 4.4−11.4 months）, which was repeated
at 1 year and 2 years follow-up in patients who had abnormal findings. When we analyzed coronary arterydiameters using Japanese Ministry of Health criteria, none of our patients could qualify for a diagnosis ofcoronary aneurysm. However, 3 had coronary artery diameters more than ＋ 2 SD when the body surface
area adjusted coronary dimensions were used.
Results. One of our patients also had increased left ventricular dimensions but also had normal ejection
fraction and shortening fraction, and there were no regional wall motion abnormalities. Mitral valve wasthickened in 2 patients and trivial mitral regurgitation was noticed in 1 patient. Repeat echocardiographydone 1 year and 2 years later on follow-up, showed persistence of thickening of the mitral valve leaflet in
one of these but there was no regurgitation. None of our patients had evidence of cardiac failure, arrhythmia or myocardial infarction. There was no mortality in this series. Thallium scans were carried out duringfollow-up on 14 patients in this cohort and 2 patients showed perfusion defects in anterior wall, septum andposterior wall of lateral ventricle.
Conclusions. We conclude that significant myocardial dysfunction and coronary artery changes due to
KD were uncommon in our cohort. We speculate that this can be attributed to the IVIG given to thepatients during the acute phase of the illness. To the best of our knowledge, this is the first study on
detailed cardiac follow-up of children with KD from a developing country.
──────────────────────────────────────────────────────────────────────────────────────────────────────────────────────J Cardiol 2007 Nov; 50（5）: 299−307

Key Words■ Kawasaki disease（India, developing country）■ Immunologic factors（immunoglobulin）■ Echocardiography（cardiac evaluation）

──────────────────────────────────────────────Departments of Pediatrics, ＊ 1Cardiology and ＊ 2Nuclear Medicine, Advanced Pediatric Centre, Post Graduate Institute of Medical
Education and Research, Chandigarh, India
Address for correspondence : Surjit Singh, MD, Department of Pediatrics, Advanced Pediatric Centre, Post Graduate Institute ofMedical Education and Research, Chandigarh-160012, India ; E-mail : surjitsinghpgi@rediffmail.com
Manuscript received March 8, 2007 ; revised June 26, 2007 ; accepted July 10, 2007

299

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Kothur, Singh, Sharma et al

INTRODUCTION
Kawasaki disease（KD）
is a generalized vasculitis
of unknown etiology, first described by Dr.
Tomisaku Kawasaki in 1967 in Japan, 1）which
affects predominantly the medium vessels and is
the commonest vasculitic disorder of childhood.2）Itis a leading cause of acquired heart disease amongchildren in developed countries,1−6）and has now
been reported from all over the world including
India. 3−5） Although this acute febrile illness
involves multiple organ systems, the major complication is the development of coronary arteryaneurysms in as many as 20−30% of patients who
are not offered treatment.1,2）Some cases of coronary artery disease and myocardial infarction inyoung adults have been attributed to missed childhood KD.7,8）A survey of 21 survivors of childhood
KD concluded that childhood KD should be included in the differential diagnosis of coronary arterydisease in young adults.8）
The use of intravenous immunoglobulin（IVIG）
during the first 10 days of the illness has beenshown to significantly reduce the risk of coronary
artery abnormalities.9−11）Other cardiac manifestations include conduction disturbances, mitral valve
regurgitation and pericardial effusion which areusually transient.11,12）
We undertook this prospective follow-up study
for the evaluation of cardiac function using
echocardiography in a cohort of children with KD
in Northern India. Computer assisted analysis of
M-mode echocardiography has been shown toaccurately assess myocardial function and twodimensional echocardiography is sensitive for identifying proximal coronary artery aneurysms.13）No
information is available on the follow-up of children with KD in developing countries. The present
study aims to bridge this gap in the literature.
SUBJECTS AND METHODSPatients and methods
The present study was conducted jointly in the
Departments of Pediatrics, Cardiology and Nuclear
Medicine of the Post Graduate Institute of Medical
Education and Research（PGIMER）, Chandigarh
from July 2002 to January 2006.
Twenty children with diagnoses of KD were followed-up for at least 3 months in the PediatricRheumatology and Immunology Clinic of theAdvanced Pediatric Centre. The diagnosis of KD

was based on standard criteria viz.2） : Fever of atleast 5 days duration ; presence of four of the following principal features,（a）changes in extremities
such as edema and/or erythema of hands and/or
desquamation usually beginning periungually,（b）non vesicular polymorphous exanthema, predominantly truncal,（c）bilateral conjunctival injection,（d）erythematous, dry fissured lips, strawberry tongue,（e）cervical lymphadenopathy ; and exclusion of
diseases which mimic KD such as Stevens Johnson
syndrome, measles and other febrile exanthemata,scarlet fever and drug reactions.
Study design
The following investigations were carried out inthe study group. Electrocardiography was recordedin all leads including long lead Ⅱ,Ⅴ3R. These wereinterpreted according to normative age-based standards for children. Chest radiography was performed. Echocardiography was done initially in theacute phase within 2−3 weeks of illness, and was
subsequently repeated after an interval of 7.9 ± 3.5
months（range 4.4−11.4 months）from the onset.
Patients with abnormal echocardiographic findings
were reexamined at 1 year and 2 years of followup. Two-dimensional echocardiography was performed（by YS）with a standard echocardiographic
machine with sector scanning instruments（General
Electrical）, Vivid 5, phased array probe of 5
（4.4−8）MHz, 84-degree sector angle with color
flow monitoring, motion mode（M-mode）, pulse
wave Doppler, continuous wave Doppler, and twodimensional octave mode with tissue harmonic
imaging facility. Two-dimensional echocardiographic examination included all standard planes
including parasternal long- and short-axis views,
apical four-chamber view, apical long-axis viewand subcostal four-chamber view. During echocardiography, a standard precordial short-axis view ofthe great vessels was recorded. Once the aortic andtricuspid valve leaflets were identified, slow superior angulation of the transducer was performed until
the tricuspid leaflet echoes were lost and the tricuspid valve ring was recognized. This method produced the characteristic linear echoes of the rightmain and proximal third of the right coronary
artery. The distal third of the right coronary artery
was recorded from the standard four-chamberedapical view and by angling the transducer either
superiorly or with appropriate clockwise or counterclockwise rotation. The left main coronary artery
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Cardiac Evaluation of Children With Kawasaki Disease

was recorded from the parasternal short-axis viewof the aorta. The bifurcation was visualized bymoving the transducer from the standard short-axis
view of the aorta and directing the transducer inferiorly and medially. Left ventricular short-axis contraction patterns were evaluated to detect asymmetrical contraction at three levels : mitral leaflet, chordae, and papillary muscle. Valvular involvement（aortic regurgitation, mitral regurgitation）was
examined. Doppler imaging was used to detect thedirection of flow and flow disturbances.
M-mode echocardiography was done according
to standard performance techniques. Parameters
included left atrial and ventricular dimensions, andleft ventricular function by ejection fraction andshortening fraction. Pericardial thickness was measured and we looked for evidence of pericardial
fluid. M-mode echocardiograms were interpreted inaccordance with normal values established in children. We judged myocardial abnormalities to bepresent if the ejection fraction was ＜ 63%, shortening fraction ＜ 27%, and ratio of left ventricular preejection time to left ventricular time was increased
for the heart rate.
Two-dimensional echocardiography evaluatedthe proximal portions of the left main coronary
artery, left anterior descending coronary artery, circumflex artery, and origin and course of right coronary artery according to standards published by
Japanese Ministry of Heath11）on which current statistics of prevalence of coronary dilation are based.
Coronary artery aneurysms were diagnosed if theinternal diameter was greater than 3 mm in children
younger than 5 years of age or 4 mm in children atleast 5 years of age ; if the internal diameter of thesegment measured was 1.5 times that of adjacentsegment ; or if the coronary artery lumen was clearly irregular. In addition, we also calculated coronary artery dimensions adjusted for body surface
area,6,14）which provide a more accurate assessmentof the size of the proximal right coronary artery orleft anterior descending coronary artery as compared with expected population norms. Any evidence of thrombus inside the dilated coronary arteries was assessed. Tissue Doppler imaging was used
to detect ischemic myocardium.
OBSERVATIONS AND RESULTS
Among the 20 patients followed-up in thiscohort, the age of onset of KD ranged between 12
months and 10 years（mean 5.4 ± 2.96 years）. The
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301

male to female ratio was 4 : 1. Laboratory investigations revealed thrombocytosis（5.0−7.5 × 105/μl）in 10 patients. Two patients who had thrombocytopenia at admission showed recovery ofplatelet counts following administration of IVIG.
Sixteen of the 20 patients had an erythrocyte sedimentation rate of more than 20 mm in the first hour.
All 20 patients enrolled in the study had received
therapy with IVIG 2 g/kg body weight in the acutephase except one patient who had received 1.5
g/kg. Eight patients received the therapy within 10
days of onset of illness, and others within 2−3
weeks after the onset of illness as they reported late
to our hospital. All patients responded dramaticallywith resolution of fever following administration of
IVIG. One patient had recurrence of fever which
spontaneously subsided after 3 days. None of thecases in this cohort had required a second course of
IVIG. In addition, all patients had received highdose aspirin 80−100 mg/kg in the acute phase andthis was reduced to 5 mg/kg/day once the fever subsided. None of the 20 patients were clinicallysymptomatic at the time of inclusion in the study.
Chest radiography in 15 of our patients during follow-up showed no abnormalities.
Electrocardiograms（ECGs）were judged according to age comparative standards for children（Table 1）.13）The PR interval ranged from 0.12−
0.2 sec（mean 0.14 ± 0.023 sec）
, which was normal
for age related upper limits except in one patient（Case 4）who had PR interval of 0.2 sec indicating
delay in conduction. T wave inversion was found in
3 patients and ST segment changes in 2 patients.
None of our patients had significant Q wave or conduction abnormalities. Repeat ECG 1 year later
showed normalization of previous abnormalities inall 3 patients.
Echocardiography in the acute phase, within 2−
3 weeks of onset of illness, and in the convalescentphase revealed no aneurysms according to the criteria of the Japanese Ministry of Health（Table 2）.11）
However, when these diameters were assessed
according to the body surface area,6,14）3 patients
had increased coronary diameters（Cases 7 and 14
could be classified as having increased right coronary artery diameter［more than 2SD］and Cases 2
and 7 as having increased left coronary arterydiameter）. However, left anterior descending coronary artery diameters were normal in all patients.
When we repeated the echocardiography according
to the protocol, coronary artery diameters normal-

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Kothur, Singh, Sharma et al

Table 1 Electrocardiographic findings
Serial No. PR interval（sec）

QRS axis

QRS duration（sec）

T waveinversion

AbnormalRepeat ECG
Q waves （1 year after initial ECG）

1

0.14

45°

0.08

−

−

Normal

2

0.12

60°

0.04

−

−

Normal

3

0.12

30°

0.08

−

−

Normal

4

0.2

60°

0.04

V1−V6

−

Normal

5

0.12

60°

0.08

−

−

Normal

6

0.12

60°

0.08

−

−

Normal

7

0.12

60°

0.06

−

−

Normal

8

0.12

60°

0.06

−

−

Normal

9

0.16

60°

0.08

−

−

Normal

10

0.16

55°

0.08

−

−

Normal

11

0.16

70°

0.05

−

−

Normal

12

0.16

45°

0.04

−

−

Normal

13

0.14

45°

0.04

−

−

Normal

14

0.12

55°

0.06

−

−

Normal

15

0.16

70°

0.08

V1−V3 L , L−, ST dep 0.5 mm

Normal

16

0.16

60°

0.08

−

−

Normal

17

0.12

70°

0.04

−

−

Normal

18

0.16

60°

0.08

−

−

Normal

19

0.14

30°

0.06

V1−V3

2 mm in V5 , ST elev L

Normal

20

0.12

65°

0.06

−

−

Normal

ECG＝electrocardiogram ; dep＝depression ; elev＝elevation.

ized in one patient（Case 7）. In the other 2 patients（Cases 2, 14）, the coronary artery diameters
remained above ＋ 2SD. No patient had regional
wall motion abnormalities at the level of chordae,
papillary muscle or mitral leaflet.
All patients underwent M-mode echocardiography according to the procedure described inmethodology section（Table 2）. One patient（Case14）had increased left ventricular dimensions［leftventricular end-systolic dimension（LVES）＝28 mm, left ventricular end-diastolic dimension（LVED）＝ 37 mm］compared with the age related
normal parameters. 13）However, she had normalejection fraction and shortening fraction, which areindicators of normal ventricular function. Ejection（mean 68.2 ± 6.1%）
fraction ranged from 60−83%
and shortening fraction ranged from 30−52%（mean 38.4 ± 5.7%）. None of our patients had evidence of pericardial effusion in the acute or convalescent phase of the disease. When echocardiography was repeated, Case 14 continued to haveincreased LVES and LVED, though the dimensions
were less than before.

The mitral valve was thickened in 2 patients, andtrivial mitral regurgitation was noticed in another
patient. Repeat echocardiography showed the mitralvalve remained thickened in 1 patient（Case 2）but
was not associated with any regurgitation, and normalized in the remaining 2 children. No othervalvular involvement was seen in any of the study
patients. Tissue Doppler imaging did not reveal any
ischemic changes in the myocardium.
As part of the unit protocol for follow-up ofpatients with KD, dobutamine stress induced thallium scintigraphic cardiac scans were also done during follow-up. Of the 14 patients who underwent
this investigation, 2 had perfusion defects in theanterior wall, septum and inferior wall of the left
ventricle.
DISCUSSION
KD is a multisystem inflammatory syndrome ofunknown etiology and variable clinical expression,
characterized histologically by the presence of vasculitis resulting in stenosis and aneurysm of thecoronary arteries.2）The diagnosis of KD is entirely
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J Cardiol 2007 Nov; 50（5）: 299 – 307

0.73

0.57

0.5

0.84

0.79

0.63

0.93

0.7

1.0

2

3

4

5

6

7

8

9

10

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Thick ML

0

0

0

0

0

Thick ML

0

66

72

66

75

77

83

70

60

68

67

36

40

30

40

45

48

44

37

37

35

31

22

28

17

26

23

21

26

24

25

26

20

16

16

20

17

11

15

24

11

31

33

30

30

35

29.6

31

25

36

35

3.1

3

3

3.5

3.3

2.1

1.7

2.5

1.9

1.7

2

2

3

2.8

2.7

2.4

2.3

2.4

2.9

1.8

2.7

1.7

2

2.3

2.3

1.6

1.7

1.6

1.9

1.6

Normal

2.7 Normal

1.8 Normal

1.5 Normal

2

2.2 Normal

1.7 Normal

1.6 Normal

1.8 Normal

1.3 Normal

1.2 Normal

NormalNot done−− aw, sep, iw

Normal−NormalNot done−−LV− aw, sep, iw

Normal−LV

NormalNormal−NormalNormalNormalNormalNormalML thickened

LCA＞2SD
RCA＞2SD

LCA＞2SD

NormalNormalNormalNormalNormalRCA＞2SD

LCA N

NormalNormal

RCA N

LCA N

NormalThick ML
LCA＞2SD

Thick MLphase）

phase）

LCA＞2SD

convalescentconvalescentThick ML,

Echo in

Echo in

LCA＞2SD

NormalRCA＞2SD

NormalNormal

LCA＞2SD

Normal−NormalNormal−（2−3 weeks） phase

Repeat Echo
（2 years after

Repeat Echoconvalescent （1 year after

Echo inleft ventricle ; N＝normal.

（Rt）
MCA＝left（right）
main coronary artery ; CX＝circumflex ; Echo＝echocardiography ; ML＝mitral leaflet ; L（R）
CA＝left（right）
coronary artery ; aw＝anterior wall ; sep＝septum ; iw＝inferior wall ; LV＝

BSA＝body surface area ; RWMA＝regional wall motion abnormalities ; EF＝ejection fraction ; LAD＝left anterior descending coronary artery ; LVES
（D）
＝left ventricular end-systolic（diastolic）
dimension ; Lt

0.65

1

（%）

Serial BSA Pericardial RWMA Valvular EF（%）Shortening LAD
LVES LVED LtMCA RtMCA LAD CX Tissue Thrombus Thallium Echo in
No. （m2） fluid
abnormality
fraction （mm/m2）（mm/m2）（mm/m2）（mm）（mm）（mm）（mm）Doppler
scan
acute phase

Table 2 Echocardiographic findings in the convalescent phase of Kawasaki disease

Cardiac Evaluation of Children With Kawasaki Disease

303

0

0

0

0

0

0

0

0

0

0

63

66

63

76

67

60

60

72

0
67

Trivial MR 67

0

0

0

0

0

0

0

0

32

36

31

32

36

52

38

41

42

36

23

24

29

16

25

15

17

17

22

15

21

24

21

18

26

13

28

16

23

12

32

32

33

28

36

22

37

28

35

27

2

3

3.1

2.3

3

2

2.3

2

3

2.3

2.4

2.6

2.8

2.3

2.5

2.2

2.7

2.2

2.5

1.8

2

2.3

2.8

1.6

2

Seen

1.5

2

2.3

1.7

1.5 Normal

2.3 Normal

2.6 Normal

1.5 Normal

Seen Normal

1.8 Normal

1.7 Normal

1.7 Normal

2.3 Normal

1.7 Normal

Normal−NormalNot done−−Normal−Not doneNormal−−Not done−NormalNot done−−Not done−NormalTrivial MR

NormalNormalNormalNormalRCA＞2SD

NormalNormalNormalNormalTrivial MR

NormalNormalNormalNormalLVES

NormalRCA＞2SD

LVED,
LVES
RCA＞2SD

phase）

phase）

LVED,

convalescentconvalescent

LVES
RCA＞2SD
NormalEcho in

Echo in

LVED,

NormalNormalNormal（2−3 weeks） phase

Repeat Echo
（2 years after

Repeat Echoconvalescent （1 year after

Echo in（Rt）
MCA＝left（right）
main coronary artery ; CX＝circumflex ; Echo＝echocardiography ; RCA＝right coronary artery ; MR＝mitral regurgitation.

BSA＝body surface area ; RWMA＝regional wall motion abnormalities ; EF＝ejection fraction ; LAD＝left anterior descending coronary artery ; LVES
（D）
＝left ventricular end-systolic（diastolic）
dimension ; Lt

0

0

0

0.63

0.47

17

0

20

0.76

16

0

0

0.5

15

0

0.73

0.53

14

0

19

0.56

13

0

1.36

0.73

12

0

18

0.41

11

（%）

（%）Shortening LAD
LVES LVED LtMCA RtMCA LAD CX Tissue Thrombus Thallium Echo in
Serial BSA Pericardial RWMA Valvular EF
abnormality
fraction （mm/m2）（mm/m2）（mm/m2）（mm）（mm）（mm）（mm）Doppler
scan
acute phaseNo. （m2） fluid

Table 2 : continued Echocardiographic findings in the convalescent phase of Kawasaki disease

304
Kothur, Singh, Sharma et al

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Cardiac Evaluation of Children With Kawasaki Disease

clinical and may be difficult for physicians notfamiliar with the disease, as there are no specificlaboratory investigations to confirm it. Many of ourpatients with KD continue to be referred with alabel of other common infectious illnesses, suggesting the lack of awareness about this condition
amongst physicians in India as in other developing
countries.3−5）Early diagnosis of KD is imperative
to avoid the risk of acute coronary vasculitis which
can occur in up to 30% of cases and which can be
minimized by prompt administration of IVIG.
In our population, KD seems to affect older children, with as many as 33% of the patients above 5
years of age.3,15）Our patients also have higher percentage of rash and changes in extremities whencompared to the western literature. In contrast, lymphadenopathy and conjunctivitis were less commonly noted.2, 3）
In this study, we found that chest radiography
was not contributory in any of the 15 patients who
underwent this examination. The ECG abnormalities suggestive of myocarditis were seen in 3 of 20
patients. Absence of pathologic Q waves suggested
that no child had significant myocardial ischemia.
There was no correlation between the ECG andechocardiogram findings. These ECG abnormalities
had normalized at follow-up done 1 year later. Low
incidence of these changes can be explained by thefact that all our patients had received IVIG. This is
in contrast to a retrospective analysis which reported ECG abnormalities in as many as 34 of 44
patients in the first week of illness. However, noneof these patients had received IVIG at that time.16）
A clinico-pathological study of 10 patients showed
KD was correlated with pathological change in theatriventricular node, and further reported that theabnormalities disappeared on follow-up.17）
In our study, echocardiography was used as amodality for cardiac evaluation which is sensitiveand specific for visualizing aneurysms of proximal
portions of both coronary arteries with improved
technique. Sensitivity of 100% and specificity of
97% were reported for detecting coronary
aneurysms in the proximal portions of the right andleft coronary arteries.18）When the measured coronary dimensions were compared with the Japanese
Ministry of Health criteria, none of our patients had
definite coronary artery abnormality（CAA）. The
low incidence of CAA was attributed to administration of IVIG（2 g/kg）. In contrast, most older studies where the incidence of CAA was 15−40%
J Cardiol 2007 Nov; 50（5）: 299 – 307

305

when treatment with IVIG was not given.7,9,10,12）A
meta-analysis included multicenter, randomized
controlled studies performed in the United States
and Japan regarding the effect of various doses of
IVIG with aspirin on the prevalence of coronary
artery abnormalities in KD.9）The prevalence ofaneurysms in the subacute phase（ 30 days）was
25.8% without IVIG and decreased to 4.8% withtherapy（2 g/kg IVIG）. The corresponding prevalence in the convalescent phase（ 60 days）was
17.6% and 3.8%. Therefore, 2 g/kg IVIG combinedwith high dose aspirin provides maximum protection against coronary abnormalities in KD.9）These
initial findings were later corroborated in several
clinical trials and supported by Cochraneanalysis. 10） The potential benefits of IVIG for
patients treated later than 10th day of illness are
uncertain. However, a retrospective study of 16
patients with KD who received delayed treatment
with IVIG（i.e. after 10 days）reported normalisation of CAA in all 7 patients compared to 4 of 7
patients not given IVIG.19）
Currently there is no consensus regarding thenorms of coronary artery diameter in children. We
used the Japanese Ministry of Health criteria11）as
well as age related norms for defining coronary
artery abnormalities. The definition of coronary
artery abnormalities were revised as coronary artery
dimensions have been shown to increase withindices of body size, such as body surface area orbody length in normal children. In particular, coronary artery dimensions adjusted for body surface
area provide a more accurate assessment of the sizeof the proximal right coronary artery or left anterior
descending coronary artery as compared withexpected population norms.6,14,20,21）A z score ＞− 2.5（i.e., a coronary dimension that is 2.5SD above themean for body surface area）
in one of these arterial
segments would be expected to occur in 0.6% of
the population without KD, and a z score ＞− 3.0 inone of these segments would be expected to occur
in 0.1% of the population without KD. Echocardiography in convalescent phase revealed coronary artery diameters ＞ 2SD above normal in 3
patients（Table 2）. In our study, we found that 15%
of patients classified as having normal coronary
arteries by the Japanese Ministry of Health criteria
would have had at least one coronary artery abnormality if the body surface area adjusted coronary
dimensions were used. More recently, the body surface area-adjusted coronary dimensions of some

306

Kothur, Singh, Sharma et alpatients with KD whose coronary arteries wereconsidered normal were shown to be larger than
expected in the acute, convalescent and late phases
when compared with references established forbody size.21）Because use of the Japanese Ministryof Health criteria may result in both underdiagnosis
and underestimation of the true prevalence of coronary dilation, coronary vessel measurements adjusted for body surface area should be compared withthose of the population without KD.6,21）None of
our patients had significant myocardial involvement. Our findings are in agreement with a thestudy of 135 patients with KD, all of whom hadreceived IVIG.20）None of the patients had myocardial abnormalities. We attribute the low incidenceof myocardial involvement in our patient population to the administration of IVIG during the acutephase of illness.
The incidence of valvular regurgitation differs
among reports.22−25）Transient valvular disease thatdevelops in the acute phase is usually attributed topancarditis. However, persistent valvular diseasecan occur due to sequelae of valvulitis and papillarymuscle dysfunction secondary to coronary stenotic
lesion.24）The mitral valve was thickened in two of
our patients, and trivial mitral regurgitation wasnoticed in another patient. One of these patients
also had myocardial perfusion defects on thallium
scintigraphy. None of them had a past history of
rheumatic heart disease. No other valvular involvement was seen in any of the study patients. Valvular
regurgitation in KD has also been reported by otherworkers. A study of 1,215 patients found that 13
patients（1.1%）had valvular disease, 12 patientswith mitral regurgitation and 1 patient had aortic
regurgitation.25）
When we repeated echocardiography in the follow-up according to the study protocol, coronary
artery diameters had normalized in one patient（Case 7）
. In the other 2 patients（Cases 2, 14）, thecorresponding coronary artery diameters remainedat more than 2SD. Resolution of coronary dilation
is similar to that noticed in other studies. However,these children need to be followed-up for longer assuch patients are known to develop intimal thickening and endothelial dysfunction.6,7,26−28）
References
1）Kawasaki T : Acute febrile mucocutaneous syndrome withlymphoid involvement with specific desquamation of thefingers and toes in children. Arerugi 1967 ; 16 : 178−222

Two-dimensional echocardiography is less sensitive for distal coronary artery aneurysms and this is
not sensitive to detect coronary artery stenosis andmicroangiopathy. Persistent perfusion defects could
represent interstitial fibrosis from myocarditis orscars from obstructive lesions due to small vessel
coronary vasculitis in which echocardiography andangiography may be normal. Thus thallium scintigraphy is required for detecting myocardial perfusion and areas of ischemia.27）
Two of the 14 patients（ Cases 5 and 8）who
underwent thallium scintigraphy had impaired perfusion defects in the septum, anterior wall and inferior wall of the left ventricle. One patient（Case 8）
also had thickened mitral valves with normal
myocardial function and coronary arteries.
Echocardiography showed no corresponding
regional wall motion abnormalities of the left ventricle. The second patient（Case 5）did not have any
echocardiographic abnormalities. Similar findings
have been previously reported.27）Four of 16 children with KD had normal coronary angiography
but showed persistent and/or transient perfusion
defects on thallium scintigraphy which indicated alack of correlation between these modalities.
Therefore, echocardiography and angiocardiography may not identify all KD patients at risk of
future myocardial ischemia. We recommend thatpatients with abnormal scintigraphy should be followed-up closely even if no definite coronary lesion
is found on echocardiography or angiocardiography.27）
CONCLUSIONS
Our study demonstrates that high dose IVIG
administered early in the course of KD is effective
in reducing the prevalence of CAA and myocardial
dysfunction. However, 15% of patients classified ashaving normal coronary arteries by the Japanese
Ministry of Health criteria had at least one coronary
artery abnormality if the body surface area adjusted
coronary dimensions were used. Two of ourpatients also had perfusion defects on thallium
scintigraphy. Our study suggests that children withKD need long term follow-up.
（in Japanese）
2）Sudel RP, Petty RE, Cassidy JT : Kawasaki syndrome. in
Textbook of Pediatric Rheumatology（ed by Cassidy JT,
Petty RE, Laxer RM, Lindsley CB）, 5th Ed. Elseiver
Saunders Co, Philadelphia, 2005 ; pp 521−538

J Cardiol 2007 Nov; 50（5）: 299 – 307

Cardiac Evaluation of Children With Kawasaki Disease3）Singh S, Bansal A, Gupta A, Kumar RM, Mittal BR :Kawasaki disease : A decade of experience from North
India. Int Heart J 2005 ; 46 : 679−689
4）Narayanan SN, Ahamed MZ, Safia M : Cardiovascular
involvement in Kawasaki disease. Indian Pediatr 2005 ; 42 :918−9225）Singh S : Kawasaki disease : A clinical dilemma. Indian
Pediatr 1999 ; 36 : 871−875
6）Newburger JW, Takahashi M, Gerber MA, Gewitz MH,
Tani LY, Burns JC, Shulman ST, Bolger AF, Ferrieri P,
Baltimore RS, Wilson WR, Baddour LM, Levison ME,
Pallasch TJ, Falace DA, Taubert KA ; Committee on
Rheumatic Fever, Endocarditis and Kawasaki Disease ;Council on Cardiovascular Disease in the Young ;American Heart Association ; American Academy of
Pediatrics : Diagnosis, treatment, and long-term management of Kawasaki disease : A statement for health professionals from the Committee on Rheumatic Fever,Endocarditis and Kawasaki Disease, Council on
Cardiovascular Disease in the Young, American Heart
Association. Circulation 2004 ; 110 : 2747−2771
7）Burns JC, Shike H, Gordon JB, Malhotra A, Schoenwetter
M, Kawasaki T : Sequelae of Kawasaki disease in adolescents and young adults. J Am Coll Cardiol 1996 ; 28: 253−
2578）Kato H, Inoue O, Kawasaki T, Fujiwara H,Watanabe T,
Toshima H : Adult coronary artery disease probably due tochildhood Kawasaki disease. Lancet 1992 ; 340 : 1127−
1129
9）Terai M, Shulman ST : Prevalence of coronary arteryabnormalities in Kawasaki disease is highly dependent on
gamma globulin dose but independent of salicylate dose. J
Pediatr 1997 ; 131 : 888−893
10）Oates-Whitehead RM, Baumer JH, Haines L, Love S,
Maconochie IK, Gupta A, Roman K, Dua JS, Flynn I :Intravenous immunoglobulin for the treatment of Kawasaki
disease in children. Cochrane Database Syst Rev 2003;（4）: CD004000
11）Kawasaki T : General review and problems in Kawasaki
disease. Jpn Heart J 1995 ; 36 : 1−1212）Chantepie A, Mauran P, Lusson JR, Vaillant MC, Bozio A :Cardiovascular complications of Kawasaki syndrome :Results of a French multicenter study. Arch Pediatr 2001 ;8 : 713−719
13）Takahashi M : Kawasaki syndrome. in Moss and Adams
Heart Disease in Infants, Children and Adolescents（ed by
Emmanouilides GC, Schneider TAR, Allen HD, GutgesellHP）, 6th Ed. Lippincot Williams and Wilkins, Philadelphia, 2000 ; pp 1216−122414）Tan TH, Wong KY, Cheng TK, Heng JT : Coronary nomograms and the coronary-aorta index : Objective determinants of coronary artery dilatation. Pediatr Cardiol 2003 ;24 : 328−335
15）Singh S, Gupta MK, Bansal A, Manoj Kumar R, Mittal
BR : A comparison of the clinical profile of Kawasaki
disease in children from North India above and below 5
years of age. Clin Expl Rheumatol 2007 ; 25 : 654−657

J Cardiol 2007 Nov; 50（5）: 299 – 30730716）Ichida F, Fatica NS, O Loughlin JE, Snyder MS, Ehlers
KH, Engle MA : Correlation of electrocardiographic andechocardiographic changes in Kawasaki syndrome. Am
Heart J 1988 ; 116 : 812−81917）Fujiwara H, Kawai C, Hamashima Y : Clinicopathologic
study of the conduction systems in 10 patients with
Kawasaki s disease（ mucocutaneous lymph node syndrome）. Am Heart J 1978 ; 96 : 744−750
18）Capannari TE, Daniels SR, Meyer RA, Schwartz DC,
Kaplan S : Sensitivity, specificity and predictive value of
two-dimensional echocardiography in detecting coronary
artery aneurysms in patients with Kawasaki disease. J Am
Coll Cardiol 1986 ; 7 : 355−360
19）Marasini M, Pangiglione G, Gazzalo D, Campelli A,
Ribaldone D, Caponnetto S : Late intravenous gamma
globulin treatment in infants and children with Kawasaki
disease and coronary artery abnormalities. Am J Cardiol
1991 ; 68 : 796−79720）Abushaban L, Salama A, Uthaman B, Kumar A, Selvan J :Do we have a less severe form of Kawasaki disease or is it
the gammaglobulin effect? Int J Cardiol 1999 ; 69 : 71−76
21）de Zorzi A, Colan SD, Gauvreau K, Baker AL, Sundel RP,
Newburger JW : Coronary artery dimensions may be misclassified as normal in Kawasaki disease. J Pediatr 1998 ;
133 : 254−25822）Newburger JW, Sanders SP, Burns JC, Parness IA, Beiser
AS, Colan SD : Left ventricular contractility and functionin Kawasaki syndrome : Effect of intravenous gammaglobulin. Circulation 1989 ; 79 : 1237−124623）Anderson TM, Meyer RA, Kaplan S : Long-term echocardiographic evaluation of cardiac size and function inpatients with Kawasaki disease. Am Heart J 1985 ; 110 :107−11524）Akagi T, Kato H, Inoue O, Sato N, Imamura K : Valvular
heart disease in Kawasaki syndrome : Incidence and natural
history. Am Heart J 1990 ; 120 : 366−372
25）Akagi T, Kato H, Inoue O, Sato N, Imamura K: Valvular
heart disease in Kawasaki syndrome : Incidence and natural
history. Am Heart J 1990 ; 120 : 366−37226）Fukushige J, Takahashi N, Ueda K, Hijii T, Igarashi H,
Ohshima A : Long-term outcome of coronary abnormalities
in patients after Kawasaki disease. Pediatr Cardiol 1996 ;
17 : 71−76
27）Fukazawa M, Fukushige J, Takeuchi T, Narabayashi H,
Igarashi H, Hijii T, Ueda K, Kuwabara Y, Otsuka M,
Ichiya Y : Discordance between thallium-201 scintigraphy
and coronary angiography in patients with Kawasaki disease : Myocardial ischemia with normal coronary
angiogram. Pediatr Cardiol 1993 ; 14 : 67−74
28）Dajani AS, Taubert KA, Takahashi M, Bierman FZ, Freed
MD, Ferrieri P, Gerber M, Shulman ST, Karchmer
AW,Wilson W, Peter G, Durack DT, Rahimtoola SH :Guidelines for long-term management of patients with
Kawasaki disease : Report from the Committee on
Rheumatic Fever, Endocarditis and Kawasaki Disease,
Council on Cardiovascular Disease in the Young, American
Heart Association. Circulation 1994 ; 89 : 916−922