Kawasaki disease (KD) was initially called mucocutaneous lymph node syndrome,1 and it still has no clear etiopathogenesis. It is a pediatric vasculitis primarily involving medium and small sized vessels, such as the coronary arteries (CAs). Previous reports have shown that 15%—25% of untreated children with KD will develop coronary injuries, which can include aneurysms, dilatation, stenosis, embolism, and even myocardial infarction and ischemic heart disease.2-4
KD is the most common acquired coronary artery disease in childhood, and children less than five years of age are at highest risk. It has been reported that the disease occurs in 19 out of every 100 000 children in the United States,5 and the incidence has increased during the last decade. Some studies report that an early therapeutic intervention with high-dose aspirin and intravenous-globulin within 10 days of fever onset can reduce the risk of developing coronary artery abnormalities by up to 10-fold.6,7 It is, therefore, crucial for physicians to identify symptoms as early as possible.
The diagnosis of KD is still based on the diagnostic criteria established by the Third International KD Conference.8 It is easy to diagnose typical KD because of its distinctive clinical symptoms; in contrast, atypical KD with its diverse clinical manifestations, is relatively difficult to diagnose. The following modalities of diagnostic imaging have been used to diagnose KD: coronary angiography (CAG),9,10 Doppler color echocardiography, and magnetic resonance imaging (MRI). Coronary angiography remains the standard diagnostic tool for assessing coronary artery lesions in patients with KD; however, its universal application is limited by the difficulty in monitoring progressive changes from aneurysms to stenotic lesions. This is because the invasive nature of technique, the small but significant procedure-related risk, and its high cost prevent frequently repeated testing. Doppler color echocardiography11 is a convenient, noninvasive, and repeatable tool for the diagnosis of KD accompanied by coronary artery aneurysms (CAAs). It can reveal the dynamics of dilatation in the proximal segments of the CA, but disease in the middle and distal segments and collateral branches cannot be clearly displayed by this technique. MRI, as reported by Greil et al,12 can provide high diagnostic accuracy for determining the size and position of a CAA, but the general rate of display of CA by MRI is insufficient because of movement artifacts and its limited spatial resolution. These limitations make assessment of mildly stenotic lesions and distal portions of the coronary artery segments uncertain.13
Multislice computed tomography (CT), especially dual-source CT (DSCT) has been used in the diagnosis of cardiovascular disease because of its improved temporal and spatial resolution. It can be used even in patients with a high heart rate, such as children. Until now, no evaluations of the use of DSCT in KD patients have been reported. In our study, we investigated the application and limitations of DSCT in patients with KD and compared the diagnostic value of DSCT with Doppler color echocardiography.
A total of 16 patients with KD from December 2006 to March 2009 were included in the study. The study included 12 boys and 4 girls, whose ages ranged from 3 months to 16 years, with a median of 3.86 years, and whose heart rates ranged from 81 to 146 beats/min, with a median of (107±18) beats/min. The diagnosis of KD was based on the diagnostic criteria of the Third International KD Conference.1 The study was approved by the Shandong Medical Imaging Research Institute and informed consent was obtained for each investigation. All the patients had, or showed clinical features suggestive of, coronary artery lesions and were followed up with Doppler color echocardiography (Phillips FDI5000, Holland) before each DSCT (Siemens, German). We obtained imaging analyses within 10 days of fever onset and at 1, 3, 5, and 12 months in each patient until complete regression.
Scanning method and measurement
Doppler color echocardiography was performed 2 days before examination by coronary DSCT. Each section was examined by an experienced radiologist who evaluated the location of the coronary artery lesions and determined the internal diameters of the left and right coronary stems or lesions. Measurements were repeated three times, and the average calculated.
The following protocol was used for DSCT. The heart rate must have been stable without frequent premature beats and arrhythmias. Holding the breath was requested of all patients who could do so; otherwise, chloral hydrate was used. Tube voltage and tube current were set according to body weight: <5 kg, tube voltage 80 kV, tube current 40-60 mAs; 5-10 kg, tube voltage 80 kV, tube current 61-80 mAs; 11-20 kg, tube voltage 80 kV, tube current 81-100 mAs; 21-40 kg, tube voltage 80 kV, tube current 101-150 mAs; >40 kg, tube voltage 100 kV, tube current 151-200 mAs. ECG-controlled tube current modulation was used with full tube current from 35% to 74% of the R-R interval. Pitch varied between 0.35 and 0.55 and automatically adapted to the heart rate. Collimation was 0.6 mm, gantry rotation time was 0.33 seconds, and the helical scan range was from the tracheal bifurcation to the diaphragmatic surface of the heart. The injection was controlled by bolus-tracking using a region-of-interest (ROI) in the ascending aorta (attenuation threshold 100 HU), and the scanning time was 4 to 6 seconds. Nonionic contrast medium (Omnipaque, 350 mgI/ml, 2 mg/kg) was injected from the cubital vein at 0.3 to 3 ml/s with subsequent flushing with 5 to 30 ml saline in order to eliminate the shadow in the cardiac atrium.
CT images were reconstructed in a monosegment mode with a section thickness of 0.75 mm and a medium smooth-tissue convolution kernel (B26f). The best reconstruction phase was manually selected from 35% to 74% of the R-R interval in 3% increments. All images were transferred to an external workstation (Leonardo; Siemens Medical Solutions, Erlangen, Germany) for further analysis. In addition to the CT axial slices, three-dimensional (3D) reconstructions, such as volume rendering (VR), multiple planar reformation (MPR), and maximum intensity projection (MIP), were used to visualize coronary artery lesions.
We determined the location of the coronary artery lesions and measured the internal diameters of the left and right coronary stems or lesions at the same time. Each of the above measurements was made by two experienced radiologists in a double-blind manner. The criteria of the Japanese Ministry of Health were used to classify coronary arteries as abnormal if the internal lumen diameter is >3 mm in children <5 years of age or >4 mm in children >5 years of age; if the internal diameter of a segment measures ≥1.5-fold larger than that of an adjacent segment; or if the coronary lumen is clearly irregular.14
Statistical analyses were performed with SPSS version 13.0. Correlation analysis was used to compare the diagnostic value of the two imaging modalities.
The characteristics of the 16 patients, included 12 with typical and 4 with atypical KD, and the results of the imaging analyses are summarized in Table 1. The types of coronary artery lesions included coronary artery aneurysms, a giant aneurysm with mural thrombus (Figure 1), dilatations (Figure 2), and a coronary artery stenosis.
In the typical KD group, seven patients did not have any coronary artery lesion as confirmed by both DSCT scans and Doppler color echocardiography; in four patients proximal coronary artery injuries were identified by both modalities; in one patient an aneurysm in the middle and distal segments of the coronary artery was detected by DSCT but was negative in Doppler color echocardiography. In the atypical KD group, three cases showed the same results with both modalities, while one case with coronary artery stenosis in the middle segment was identified by DSCT but not detected by Doppler color echocardiography. DSCT showed coronary artery injury in 9 of the 16 patients, while Doppler color echocar- diography showed coronary injury in 7 of the 16 patients. The comparison of the diagnostic results for the two methods is summarized in Table 2. The location, degree, and scope of the coronary artery lesions were shown clearly by DSCT in all 9 patients; whereas only seven of the 9 lesions were also visualized by Doppler color echocardiography. The two coronary artery lesions that were undetected by Doppler color echocardiography were an ectasia located in the middle and distal segments of the coronary artery in patient 14 (Figure 3) and a stenosis in the middle segments of the left anterior descending coronary artery in patient 16 (Figure 4). Kappa value was 0.768 (≥0.75), there was a good correlation between the two imaging modalities. Furthermore, signs such as double-outlet right coronagy artery, variation of coronary artery origin, and double superior vena cava could only be demonstrated clearly in DSCT. On the other hand, pericardial effusion, ventricle enlargement, and mobility of the cardiac atrium or ventricle could be visualized clearly in both DSCT and Doppler color echocardiography.
The coronary artery lesions in 6 patients disappeared during long term follow-up. The coronary artery dilatation disappeared in 1 patient by 4 weeks, another 2 patients within 1 to 3 months. The lesions resolved within 3 to 6 months in 2 other patients and within 1 year in 1 patient. The coronary artery lesions persisted beyond 1 year in only 3 patients, 2 with coronary artery aneurysms and 1 with coronary artery stenosis.
Involvement of the coronary artery is still considered to be a major complication of KD, which greatly affects the morbidity and mortality of these patients. It has been reported that high-dose aspirin and intravenous-globulin can significantly reduce the risk of coronary artery involvement and improve prognosis during the acute stage.15,16 As soon as a patient has clinical signs and symptoms suggestive of KD, a prompt and systematic evaluation of the coronary artery is necessary, because timely diagnosis and medical intervention can prevent complications. Invasive coronary angiography has been regarded as the gold standard for diagnosis and follow-up of coronary artery abnormalities in patients with KD. Recent progress has been made in multislice CT coronary angiography, which has led to the possibility of employing this non-invasive imaging modality as a viable alternative method for the assessment of coronary artery lesions, such as, aneurysms, stenosis, and occlusions. DSCT has significantly higher diagnostic accuracy and provides more detailed information about coronary artery lesions. High quality DSCT angiographic images of the coronary anatomy can be clearly displayed at almost any heart rate because of its 83-msec temporal resolution. This was important in our study because KD usually occurs in children less than five years of age who have rapid heart rates. In this study, the average heart rate of the patients with KD was 107 beats/min. The pitch of DSCT is automatically adapted to the heart rate; the faster the heart rate the greater the pitch, which shortens the scan time and reduces the radiation dose. In addition, it tracks and adjusts the scan dosage for every circulation, which can further reduce the radiation dose.17 Moreover, the post-processing 4-D evaluation provides the possibility to show the dynamics of the cardiac muscle mobility, valvar stopcock, and blood flow, and allows objective evaluation of the scope and degree of heart lesions.18
To the best of our knowledge, there is no previous publication showing the use of DSCT in the diagnosis of KD with coronary artery involvement. In the current work, DSCT showed coronary artery injury in 9 patients, while Doppler color echocardiography showed coronary injury in 7 patients. There was a good correlation between the two imaging modalities. Analyzing their coronary artery images, we found the proximal portions of the main trunk of the coronary artery were often involved. We also found good agreement in the determination of the lesions in the proximal portion of the coronary artery between DSCT and Doppler color echocardiography. However, in the study, DSCT showed one with aneurysm in the middle and distal segments of the coronary artery and one with stenosis, while which could not be displayed by Doppler color echocardiography. Obviously, the diagnostic value of DSCT is superior to that of Doppler color echocardiography.
We also found congenital anomalies of the coronary artery and superior vena in 2 patients by DSCT scanning. Although these congenital anomalies cannot result in serious complications to the cardiovascular system, awareness of them should be helpful for the design of therapeutic strategies.
Although most patients with KD and coronary artery involvement can completely recover, coronary artery stenosis still develops in 5%-19%. This condition, which cannot be adequately visualized by Doppler color echocardiography, is now reported to be a potential risk factor for adult ischemic heart disease and sudden death in early adulthood.19 Therefore, regular follow-up of the coronary artery status is essential for the management of patients with KD.20 In adolescent patients with KD, good agreement between multislice spiral CT and CAG for the detection and follow-up of CAAs and stenosis has been reported.21-23 As mentioned previously, children less than five years of age are at highest risk, and the patients in our study were mostly young children. In our study almost all the patients were followed up by DSCT. We found that most coronary artery lesions were resolved within a year, but the coronary artery lesions still remained in 3 patients, 2 with coronary artery aneurysms and 1 with coronary artery stenosis. DSCT not only directly displays the dimension, shape, and position of the lesions but also the formulation of walls of the CAAs and the scope of the plaque. One patient had coronary artery stenosis that could not be detected by Doppler color echocardiography, therefore DSCT can play a very important role in discovering and following up coronary artery lesions.
A limitation of this study is the small sample size because of the relatively low incidence of KD. In addition, DSCT cannot provide accurate and detailed information about some parameters, such as hemodynamics and blood oxygen content. DSCT also cannot be performed in those patients with severe arrhythmia.
In conclusion, DSCT scanning should be used routinely for patients whose condition is suggestive of KD. It can reveal coronary artery lesions in patients with KD in a timely manner and help with therapeutic decision-making to improve the prognosis. In the future, DSCT has the potential to become a standard diagnostic tool in evaluating coronary artery abnormalities before and after treatment or as follow-up in patients with KD.
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