Necessity of topics Kawasaki disease has many organ involvements, but coronary tery involvement is the most serious problem of the disease, since the coronary artery inflammation is pro
Trang 1INTRODUCTION THESIS
1 Necessity of topics
Kawasaki disease has many organ involvements, but coronary tery involvement is the most serious problem of the disease, since the coronary artery inflammation is progressing silently for several months, several years leading to intimal thickening, arteriosclerosis, calcification and myocardial infarction even sudden death Thus, long-term follow-up of cardiac lesions, especially of giant aneurysms
ar-is necessary At the acute stage, when the children are small, the use
of echocardiography is a basic and sufficient for diagnosing the nary artery involvement However, as children grow up, the use of echocardiography will be limited, especially in assessment of steno-sis or in distal segment Therefore additional diagnostic imaging methods are needed Coronary angiography is the gold standard in assessment but is invasive method, so it is not used regularly The introduction of a multiple slice computed tomography 256 (MSCT-256) allowed the estimation of adequate and accurate coronary le-sions in children However, application of MSCT-256 in the diagno-sis of coronary artery disease in children in general and children with Kawasaki in particular has not been applied much, especially in Vi-etnam Therefore, we conducted the research project "Evaluate pro-gress of coronary artery involvement in Patient with Kawasaki dis-ease” with the following objectives:
coro-1 Evaluate progress of coronary artery involvement and
relat-ed factors for the regression coronary artery involvement in children with Kawasaki disease
2 Assess the value of diagnostic imaging methods raphy, multiple slice computed tomography 256- MSCT 256) in evaluat-ing and monitoring coronary lesions in Kawasaki disease
(echocardiog-2 New contributions of the thesis
The study used a MSCT-256 with echocardiography to monitor and evaluate coronary lesions in long-term in children with Kawasaki disease with long- term follow-up MSCT- 256 allows evaluating the
Trang 2entire system of coronary artery from the proximal to distal segment, assessing the aneurysm, stenosis and calcification Image in MSCT-
256 is honest, objective and accurate Thus, the study provides a comprehensive and accurate assessment of coronary lesions suffi-ciently, in overview about this progress We hope that, it could pro-vide readers with the information about the role of each imaging method (echocardiography, MSCT-256) in monitoring and evalua-tion of coronary artery involvement, which defenses on time after on-set Therefore, the topic is scientific, practical value, contributing greatly
in improving the quality of treatment of coronary artery disease in dren, especially children with Kawasaki disease The topic also contrib-utes to the study of Kawasaki disease in Vietnam
chil-3 Thesis layout
The thesis consists of 127 pages, apart from the introduction (2 pages), the conclusion (2 pages) and the recommendation (1page) also has four chapters include: Chapter 1: Overview (38 pages); Chapter 2: Materials and Methods (16 pages); Chapter 3: Results (30 pages); Chapter 4: Discussions (38 pages) The thesis consists of 35 tables, 12 pictures, 4 charts, 3 diagrams and 133 references (5 in Vi-etnamese; 128 in English) and appendix
Chapter 1: LITERATURE REVIEW
1.1 Progress of coronary artery involvement
Inflammation of the entire vascular wall progresses silently ing to damage of the middle layer of blood vessels, smooth muscle cell necrosis, disrupting normal structure into blood vessel Vessels become weakened and vascular aneurysm appears Endothelial dam-age and dysfunction of the endothelium cells cause platelet deposi-tion, which is the risk of blood clots forming, narrowing the arteries causing the arteries to become clogged, either by thrombosis, or by narrowing of the arteries (Figure 1.2)
Trang 3lead-Figure 1.2 Progression of coronary artery involvement
1.2 Criteria for cardiac lesions in Kawasaki: Coronary artery
anomaly is defined at least one of the findings on echocardiography presented:
1.2.1 According to Japanese Ministry of Health (JMH)-1998
Absolute internal lumen diameter ≥ 3mm in children aged younger than 5 years or ≥ 4mm in children aged 5 years or older
A segmental internal diameter of any segment ≥1.5 times greater than that of an adjacent segment
Coronary artery walls are noticeably abnormal
Studies on coronary artery involvement in KD mostly follow this standard
1.2.2 According to the American Heart Association (AHA) 2004:
Internal diameter ≥ + 2.5 SD normal value by skin area
The inner diameter of a segment is 1.5 times greater than the adjacent segment
Abnormal coronary artery vessels, bright light around the vessels and coronary arterial diameter losing tapping
1.3 Classification of coronary artery aneurysms (AHA -1994)
Small aneurysms: Lumen diameter < 5mm
Medium aneurysms: Lumen diameter ≥ 5mm và < 8mm
Trang 4 Giant aneurysm: Luminal diameter ≥ 8 mm
1.4 Classification of severity: According to JMH 2008
Grade I: No dilated lesions in the acute phase
Grade II: Transient dilatation in the acute phase: Mild, sient dilation that normalizes after 8-10 weeks
tran- Grade III: Regression: Residual aneurysms formation lent to or greater than dilation by 8-10 weeks that have completely nor-malized by 1 year after onset but grade V is not applicable
equiva- Grade IV: Residual coronary artery aneurysm is seen more than 1 year later and to whom grade V is not applicable
Grade V: Coronary artery stenosis
Va: No ischemic findings
Vb: Ischemic findings
JMH- 2013 revised, shortened the time of grade II and III to 30 days
1.5 Study of coronary artery involvement in patient with Kawasaki 1.5.1 In the world: There have been many studies on coronary ar-
tery involvement, evolution of this involvement and many topics about the factor related to the evolution of coronary artery lesion as well as diagnostic methods for monitoring lesions In Japan, there is a Kawasaki Specialized Research Center There are so many specialists
in the field of genetics, pathology, and treatment in the world
1.5.2 In Vietnam: Kawasaki disease has been diagnosed for the
last two decades There have been a number of studies on the disease, but almost of them has been clinical, subclinical findings, and coro-nary involvement in acute phase There is less long-term follow-up study on later In 2008, Dang Thi Hai Van's research was also on this subject, but her subjects with follow-up time no longer enough, most
of her assessments are in acute and sub-acute phase There were its on follow-up period, and means for monitoring lesion In particu-lar, there was no published study about the role of MSCT in evaluat-ing coronary artery lesions in Kawasaki KD with large numbers of
lim-KD
Trang 5Chapter 2: MATERIALS AND METHODS
2.1 Research subjects: 89 patients with Kawasaki disease (KD) 2.1.1 Standard KD selection: Enough of 3 conditions
+ Was diagnosed with KD based on the diagnostic criteria of the Japan National Committee for Kawasaki Disease and the American Heart Association, treated at the National Hospital of Pediatrics In-clude:
• 24 KD diagnosed before 2012
• 65 KD diagnosed from January 2012 to June 2016
+ Has at least 1coronary artery involvement grade III or higher according to Japanese Ministry of Health (JMH-2008), including:
• 24 KD diagnosed before 2012: Coronary artery involvement detected on echocardiography existing after 12 months onset (≥ grade IV)
• 65 KD diagnosed from January 2012 to June 2012: Residual coronary artery involvement on echocardiography after 2 months on-set (≥ grade III)
KD was identified to have coronary lesions in the acute phase, which were followed for at least the first 3 months and subsequent months according to the severity of the lesion
+ KD were monitored by clinical examination, gram, echocardiography and MSCT-256 was done at least once time during follow-up MSCT screening is only conducted after an acute phase of at least 3 months The patients having sequela in the first MSCT, regression markedly aneurysm or suspect of stenosis on echocardiography during follow-up and the agreement for the second time MSCT will be done the second MSCT
2.1.2 Exclusion criteria: Kawasaki KD with ≥1 condition:
+ Coronary artery involvement grade I, grade II or
Trang 6So the number of KD needs to roll in: 73 KD 89 KD admitted to the study were eligible for sample size
Objective 2: 89 KD, each MSCT- 256 could assess at least 4 principal coronary arteries: Left main coronary artery (LMCA); Left anterior descending (LAD); Left Circumflex (LCx); RCA (right cor-onary artery) These coronary arteries are also evaluated on echocar-diography at each time Thus, the number of coronary arteries is evaluated at least: 89 * 4 = 356 With this number of coronary arter-ies evaluated, it is satisfactory for the statistical evaluation algo-rithms, for assessment the role of these two imaging methods
2.2.3 Research material: Echocardiography was done on the
Hewlett-Packard SONO 5500 and EnVosor with the leading detect 7.5/5.5 MHz and 5.0/ 3.5 MHz at National Hospital Pediatric by Pe-diatric Cardiologist MSCT-256 was done on Siemens Sensation ma-chine, Somatom definition flash 256 at Bach mai Hospital
2.2.4 Analysis data: On SPSS 16.0
Chapter 3: RESULTS
We used MSCT -256 instead of a coronary angiography bining echocardiography in order to evaluate the progress of coronary arteries involved in 89 KD who have at least 1 coronary artery injury
com-≥ grade III according to the JMH
3.1 Patient characteristics
3.1.1 Clinical characteristics (table 3.1): 89 KD included 64
male; 56 children with aged onset ≤12 months; 71 typical KD; 83 children received IVIG; 44 infants using gamma globulin (IVIG) before 10 days and 21 infants with IVIG resistance, only 5 KD recurred
3.1.2 Coronary artery involvement at base line:
Trang 7Coronary involvement is confirmed at 2 months after onset: 89
KD with a total of 265 coronary arteries involved, including LMCA (85; 32.1%); LAD (77; 29.0%); LCx (23; 8.7%); RCA (80; 30.2%)
Of these, 94 were aneurysm (94/265; 35.5%) The number of nary arteries involved in each patient was: 1coronary artery involved (6; 6.7%); 2 coronary arteries involved (12; 13.5%); 3 coronary arter-ies involved (49; 55.1%) and 4 coronary arteries involved (22; 24.7%) 42 (47.2%) KD with small aneurysm; with medium aneu-rysm (36; 40.4%) KD and giant aneurysm (11; 12.4%) KD (table 3.2 table 3.4)
coro-3.1.3 Coronary artery involvement on echocardiography when taking MSCT for the first time
Table 3.7 Coronary injuries on echocardiography at taking MSCT for the first time
* Time after onset MSCT done; ** n: number patient
Remarks: The majority of KD underwent MSCT for the first time within a year after onset (38/89) KD Almost all of aneurysm has been seen on echocardiography in one year after onset (23/38 KD) The years later, at the time of MSCT, on cardiography, aneu-rysm is rarely seen
3.1.4 General information about KD before taking MSCT
MSCT were done at least once time for all patients, among the 89
KD, 63 KD with MSCT done once time and 26 KD with MSCT done twice Of the 26 KD undergoing MSCT twice, there were 5 KD, the first of which was done before 2012 Clinical examine, echocardiog-raphy realized before taking each MSCT: 1-7 days
Table 3.8 General information about KD before taking MSCT
Trang 8Age of
disease*
MSCT for the first time (n=89)
MSCT done once time (n=63)
MSCT done 2 times
∑ **
First time (n=26)
Second time (n=26)
Median:
15
22.4±23.0 (3-120)
Median:
15
35.9±40.0 (2-125)
Median:
20
67.2±50.1 (12-204)
Median:
31
37.1±28.7 (8-163)
Median:
28
35.9±40.0 (2-125)
Median:
20
67.2±50.1 (12-204)
*: Time after onset MSCT done; **: Number MSCT done
Remarks: Minimum age of disease, the minimum real age of KD taking MSCT is 2 months and 6 months, respectively
3.2 Progress of coronary arteries followed by diagnostic imaging
89 KD with coronary artery involvement in grade III or more severe, duration of follow-up ranged from 3-204 months; median: 20 months We saw:
3.2.1 Regression: The regression rate was 50.6% (45/89) KD
and the regression rate was 73.2% (194/265) coronary arteries volved
in-Table 3.11 Rate of regression of coronary arteries involved according to the time after onset
Time after onset
Regression No-regression Total
Trang 9Remarks: The regression rate assessed after 12-72 months onset was significantly higher than that in the first 12 months after onset (p
<0.001) There was no difference in regression rates between the
Compare LMCA vs LAD/ RCA, p <0,001; * p>0,05
Compare LMCA vs LCx; LCx vs RCA; LAD vs LCx/ RCA, p>0,05
Remarks: In general, the regression rate of the left coronary artery system is higher than right coronary artery LMCA regression rate was higher than LAD and RCA (p <0.001) Residual irreversibility (aneurysm /± calcification, stenosis) in RCA was also highest (9/33; 27.2%; p> 0.05)
Table 3.10 Progress of coronary artery involvement according
to their classification of size
Trang 10Table 3.13 Progress of coronary artery involvement according to their classification of size and their respective arteries
* Compare LMCA vs LAD/RCA
Remarks: In the small and giant aneurysms, there was no ence in regression rates between arteries (p>0.05) In medium aneu-rysms, the rate of regression of the LMCA was higher than that of LAD and the RCA (p<0.05) However, there was no difference in regression rate among the rest of the coronary arteries
Trang 11differ-Table 3.12.Progress of coronary artery involvement according to their respective arteries and their classification of size
Remarks: Lumen diameter is more likely to affect later regression than the respective arteries Differences were noted in all three arter-ies: LMCA; LAD and RCA (p<0.05)
(n=2)
1 50.0 1 50.0 Giant aneurysm
(n=9)
1 11.1 8 88.9
Trang 123.2.2 New and expanding aneurysms: Of the 26 KD identified for coronary artery sequela at the first time on MSCT, the second MSCT was taken Results of table 3.16 show that 3 KD (11.5%) with
4 different aneurysm sites showed newly Consider these 3 KD: the age of disease with MSCT done for the first time: range: 4-106 months; Age of disease at MSCT for second time: 22-124 months; distance time between 2 times for MSCT range: 18-36 months De-scribe the size of a new and expanding aneurysm between the first time and second time as follows: Patient N 0 1 has two coronary arter-ies, whose lumen diameter increased in size (LAD: 2.5mm (3.1SD)/3.3mm (7.1SD); LCx: 1,9mm (2, 7SD)/2,8mm (6 SD) Pa-tient N0 2 has a new aneurysm that appeared at the coronary artery without previous lesion (LCx aneurysm 2 * 7.5mm) Patient N0 3 has
a new aneurysm appearing in previous coronary artery involved (RCA aneurysm: 8 * 10mm/3.7 * 10mm and 8.3 * 10mm)
3.2.3 Stenosis: 5/89 (5.6%) KD with 7 coronary arteries became
stenosis in many grades, from very slight to severe stenosis Age of set KD varies from 7.5 to 42 months; Age of disease when stenosis is detected: 10-12 years; Actual age ranges from 11 to 16 years All of them had a medium or giant aneurysm at sub-acute phase 4/5 KD were severely stenosis (>80%) and all had RCA stenosis (5/5), only 2/5 KD with LAD stenosis (table 3.17)
on-3.3 Value of echocardiography, MSCT- 256 in the assessment, monitoring of coronary artery involved in patients with Kawasaki 3.3.1 Role of echocardiography
Table 3.21 Value of echocardiography versus MSCT in detecting coronary aneurysm
Remarks: Sensitivity: 41.7% Specificity: 96.0%
Positive Predictive Value: 80.9% Negative Predictive Value: 80.4%
Trang 13Table 3 22 Value of echocardiography versus MSCT in detecting coronary aneurysm in case of age of disease ≤ 12 months
Remarks: Sensitivity: 65% Specificity: 94%
Positive Predictive Value: 88.6% Negative Predictive Value: 81.3%
Table 3 23 Value of echocardiography versus MSCT in detecting coronary aneurysm in case of age of disease > 12 months
Remarks: Sensitivity: 22.2% Specificity: 96.6%
Positive Predictive Value: 66.7% Negative Predictive Value: 80.0%
Table 3.26 Progress of coronary aneurysms follow-up on diography
n Average lumen diameter (SD)
Rate of regres-sion (%)
LMAC 26 13.3±5.5 8 7.5±4.7 69.2 <0.01 LAD 29 22.1±5.0 15 10.2±10.0 48.3 <0.01 LCx 4 31.0±23.6 4 13.2±12.5 0.0 >0.05
RCA 35 24.4±6.8 18 18.8±12.3 48.6 <0.05