279
Multidetector-Row CT
for Assessment of Kawasaki Disease
TORU SAKUMA, MD AND KUNIHIKO FUKUDA, MD
KAWASAKI DISEASE GENERAL
Kawasaki disease is an acute febrile illness, causing mu- cosal inflammation, skin rash, and cervical lymphadenopathy, recognized most often in children younger than 4 yr of age. It was first described by Dr. Tomisaku Kawasaki in Japanese literature in 1967 (1), and then in English in 1974 (2). The disease is of unknown etiology that produces a systemic vascu- litis, which is most severe in the medium-sized arteries, and especially prominent in the coronary arteries. This can be asso- ciated with considerable morbidity and mortality, mostly the result of myocardial involvement and coronary artery compli- cations such as aneurysm, calcification, and stenosis. In Japan as well as in North America, Kawasaki disease is presently a leading cause of acquired heart disease in children (3).
DIAGNOSTIC CRITERIA
The diagnosis of Kawasaki disease is made according to the guidelines prepared by the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association (Table 1) (4), and the Japan Kawasaki Disease Research Committee (5), because of the absence of a specific laboratory test. The principal diagnostic criteria of Kawasaki disease are persistent fever, conjunctival injection, inflamed oropharyngeal mucosa, changes in the peripheral extremities, erythematous rash, and cervical lymphadenopathy. At least five of these six principal diagnostic criteria should be satisfied to establish a diagnosis of Kawasaki disease. Where coronary aneurysms are recognized by transthoracic echocardiography or coronary angiography (CAG), patients with four of the above diagnostic criteria can also be diagnosed with Kawasaki disease.
TREATMENT AND MANAGEMENT
Standard initial treatment involves intravenous administra- tion of high-dose γ globulin and oral administration of aspirin.
Treatment is started preferably within the first 10 d from the onset of illness (6–8). Two mg/kg intravenous γ globulin (IVGG) combined with at least 30 to 50 mg/kg/d aspirin pro- vides maximum protection against development of coronary abnormalities after Kawasaki disease. Gamma globulin helps
to prevent coronary artery complications, and aspirin clears acute inflammatory symptoms (9). IVGG therapy has reduced both the morbidity of Kawasaki disease and the apparent inci- dence of coronary artery abnormalities from approx 20–25% to less than 5% at 6–8 wk after initiation of therapy (6). In the pre- IVGG treatment stage, the incidence of coronary aneurysm in acute Kawasaki disease was 25%, 55% of which showed regression on follow-up angiography. This is a characteristic phenomenon in Kawasaki disease. Regression is likely to occur within 1 or 2 yr after onset, and it is unlikely to occur more than several years after onset (10–12). During follow-up, ischemic heart disease developed in 4.7% and myocardial infarction in 1.9%. Death occurred in 0.8% (13). The standardized mortality ratio of Kawasaki disease was 1.25, but for the male group with cardiac sequelae was 2.35. So the mortality rate among male patients with cardiac sequelae due to Kawasaki disease seemed higher than that in the general population (14). The number of patients with cardiac lesions 1 mo after onset has decreased year by year, and that is possibly attributable to the increase in the proportion of patients treated with IVGG and an increase in the dosage (15).
Long-term management of Kawasaki disease, which is based on risk stratification, is also shown by the research committee, and risk level categories are summarized (3). Patients with a normal coronary artery, evaluated by echocardiography or CAG during the acute stage of Kawasaki disease, have little morbidity in childhood, and no strict follow-up is usually required.
ASSESSMENT OF CORONARY ARTERY ECHOCARDIOGARPHY
The initial evaluation and follow-up of the coronary arterial lesions in Kawasaki disease are done by echocardiography, because it is considered to be the most useful and essential method to evaluate coronary aneurysms. Evaluation of coro- nary artery morphology should include quantitative and quali- tative assessment of the inner diameter of the vessels. When the coronary artery diameter is larger than normal but a segmental aneurysm is not apparent, the vessel is described as ectatic.
Aneurysms are classified as small (less than 5 mm in internal diameter), medium (5 to 8 mm in internal diameter), or giant (more than 8 mm in internal diameter). Many publications have demonstrated the high efficacy and accuracy of echocardio-
From: Contemporary Cardiology: CT of the Heart:
Principles and Applications
Edited by: U. Joseph Schoepf © Humana Press, Inc., Totowa, NJ
26
Table 1 Diagnostic Criteria Principal Clinical Findings a
Fever persisting at least 5 d b and the present of at least four of the following five principal features:
1. Changes in extremities:
a. Acute: erythema and edema of hands and feet
b. Convalescent: membranous desquamation of fingertips 2. Polymorphous exanthema
3. Bilateral, painless bulbar conjunctival injection without exudates
4. Changes in lips and oral cavity: erythema and cracking of lips, strawberry tongue, diffuse injection of oral and pharyngeal mucosae
5. Cervical lymphadenopathy (=1.5 cm in diameter), usually unilateral
a Patients with fever and fewer than four principal symptoms can be diagnosed as having Kawasaki disease when coronary artery disease is detected by 2D echocardiography or coronary angiography. Other diagnoses should be excluded. The physician should be aware that some children with illness not fulfilling these criteria have developed coronary artery aneurysms.
b Many experts believe that in the presence of classic features, the diagnosis of Kawasaki disease can be made by experienced observers before d 5 of fever.
Adapted from ref. 4.
graphy in detecting and characterizing coronary artery diseases (16,17). It has been reported that echocardiography has 98%
sensitivity and 95% specificity in the diagnosis of left main coronary artery aneurysms in comparison with CAG. How- ever, echocardiography is less sensitive in detecting right coro- nary artery (RCA) lesions, as the middle part of the RCA is located behind the sternum and the distal part of RCA is the furthest away from the chest wall. In addition, it is impossible to evaluate small aneurysms in the peripheral branches and the lumens of calcified aneurysms by echocardiography. There is also a limitation in the accurate evaluation of the degree of stenosis and the size of intramural thrombosis within aneu- rysms. Furthermore, visualization and characterization of the coronary arteries through transthoracic echocardiography become progressively more difficult as the child grows.
CORONARY ANGIOGRAPHY
CAG offers complete images of coronary arteries and more detailed definition of coronary artery anatomy than echocardiography, making it possible to detect coronary artery stenosis or thrombotic occlusion and to determine the extent of collateral artery formation. However, there are certain risks associated with this procedure as a result of its invasive nature and the exposure to ionizing radiation, as well as its being more expensive. Whether to use CAG should be determined on a risk-vs-benefit balance, including abnormal findings on echocardiography, symptoms or signs of ischemia, ausculta- tory evidence of valvular regurgitation, evidence of cardiac dysfunction, and the need for intracoronary thrombolytic treatment (3).
Whether or not regression may reverse and eventually develop into stenosis is uncertain at the present time. However, postmortem examinations of some patients with angiograph- ically documented regression of coronary artery aneurysm have revealed intimal proliferation and fibrosis not apparent on the angiogram (18). On intravascular ultrasound imaging (IVUS), the regressed coronary aneurysms also demonstrated a marked thickening of the intima with or without calcification, which bore a striking resemblance to early atherosclerotic lesions (19,20). The coronary artery wall, at the site of the regressed
aneurysm, had poor distensibility and was stiff on examination with intracoronary isosorbide dinitrate (21). These findings suggest that regressed ectasia and aneurysm has potential risk for later complications, even in cases of normal CAG. There- fore, long-term follow-up is recommended in cases of asymp- tomatic transient aneurysm, to screen for development of premature coronary artery atherosclerosis in adulthood.
MAGNETIC RESONANCE IMAGING
Electrocardiogram (ECG)-gated magnetic resonance imag- ing (MRI) has also been used for the noninvasive evaluation of the aortic root and the major proximal portion of the coronary arteries (22). Recent development of magnetic resonance (MR) hardware and rapid acquisition pulse sequences enables high resolution MR angiography (MRA) of the coronary arteries.
Sensitivity, specificity, accuracy, and negative predictive value for patients with coronary artery disease by coronary MRA were 94%, 45%, 75%, and 82% respectively, compared with CAG (23). Free-breathing 3D coronary MRA also accurately defines coronary artery aneurysms in patients with Kawasaki disease (24). However, several data acquisitions are needed along the major axis of the arteries because of the limitation in the volume coverage of the scans. The scanning time of approx 30 min is a relatively long time for young children and adoles- cents. In addition, voxel size of 0.7 × 1.0 × 1.5 mm is not adequate for 3D imaging in comparison with the isotropic data obtained with multidetector-row CT (MDCT).
ASSESSMENT OF CORONARY ARTERIES BY MDCT INTRODUCTION
Single-slice helical CT has a limited role in the management of Kawasaki disease because of cardiac motion artifacts due to long acquisition times and lack of ECG gating, although there has been one report presenting two cases of Kawasaki disease with unrecognized coronary artery aneurysms detected by single-slice helical CT (25).
Electron beam CT (EBCT) is an effective, noninvasive method of identifying coronary artery aneurysms. Frey et al.
reported in their series that 9 of 10 coronary artery aneurysms in Kawasaki disease were visualized with EBCT. In one false
Table 2 Scan Protocol
SOMATOM Volume Zoom SOMATOM Sensation 16
Collimation 4 × 1 mm 12 × 0.75 mm
Gantry rotation time (ms) 500 420
Temporal resolution (ms) 125–250 105–210
Spacial resolution 0.7 × 0.7 × 1.25 0.7 × 0.7 × 0.8
Table feed (mm/rotation) 1.5 2.8
Tube voltage (kV) 150 120
Maximum tube current (mA) 500 500
Contrast agent (mL) 2.0 × body weight (BW) 2.0 × BW
Scan delay time (s) 20 bolus tracking
Scan time (s) 35 10
case, two contiguous aneurysms were mistaken for a single aneurysm. The inability to resolve the aneurysms as sepa- rate structures was probably due to 8-mm section thickness in this case (26). Spatial resolution of EBCT is suboptimal for the evaluation of coronary arteries compared with that of MDCT.
Z-axis collimation of EBCT is up to 3 mm, while in 16-row MDCT it is 0.75 mm. Another problem with EBCT is that the prospectively ECG-triggered sequential method cannot obtain phase-constant cardiac volume imaging during the scan, which results in potential image degradation.
MDCT with retrospective ECG gating is considered a well- suited modality for noninvasive diagnosis of the coronary arteries, as it can optimize temporal resolution, spatial resolu- tion, and volume coverage.
METHOD
Three-dimensional volume data were obtained with MDCT (SOMATOM Volume Zoom and SOMATOM Sensation 16, Siemens AG, Medical Solutions) (Table 2). Average scan range was 100 mm. All image acquisitions were performed in deep inspiratory breath-hold among patients who were able to do so, and those patients who could not do so were allowed to breath freely under sedation with chloral hydrate to achieve an adequate study. The injection of 2 mL/kg of 370-mgI/mL non- ionic contrast medium (iopamidol) was performed via a peri- pheral intravenous route during one breath-hold, with simultaneous registration of the ECG signal also being per- formed. The injection speed ranged from 1 to 3 mL/s, depend- ing on the patient’s age and size. The ECG signal was used to reconstruct the images at identical time points, about 400 ms before the next R wave. For 3D reconstruction and visualiza- tion of the coronary arteries, curved multiplanar reformation (MPR) and maximum intensity projection (MIP) techniques were applied (Heart View CT, Siemens AG, Medical Solu- tions). Curved MPR images were rendered along the course of each coronary artery from the axial data set, while MIP images were produced in the same way with 3-mm thickness.
DETECTABILITY BY MDCT
MDCT findings in 70 cases with Kawasaki disease were analyzed, where the coronary arteries were subdivided into
proximal and distal parts. The area within reach of echocardiography was defined as the proximal part and the region beyond the reach of echocardiography as the distal part.
The visibility of coronary arteries was 93.6% in the proximal part and 62.9% in the distal part. In the proximal part, 18 cal- cifications, 24 aneurysms, 19 both calcification and aneurysms and one stenosis were found. The sensitivity of MDCT was 94.3% in the detection of abnormalities within the proximal segments of the coronary arteries, and the specificity was 100%
when echocardiography was used as the gold standard. In the distal part, where echocardiography cannot reach, 16 calcifica- tions, 2 aneurysms, 8 both calcifications and aneurysms, and 4 stenoses were detected.
REPRESENTATIVE CASE STUDIES Case 1: 19-Yr-Old Male
This patient presented with continuous fever, conjunctival injection, erythema and edema of hands and feet, and poly- morphous exanthema. He was diagnosed with Kawasaki dis- ease at 20 mo from birth. The patient was treated with aspirin and dipyridamole, recovering within 25 d. Echocardiography revealed coronary aneurysms in the proximal part of the RCA and left coronary artery (LCA). The initial CAG was per- formed 2 mo after the onset, because of abnormal Q wave and arrhythmias, and revealed a coronary aneurysm with stenosis and thrombus in the RCA and an aneurysm with stenosis in the LCA. Repeat coronary angiographies were performed at the ages of 5, 8, 11, 14, and 19 yr. At the age of 19, left circumflex (LCx) obstruction was discovered, and thallium-201 myocar- dial perfusion scintigraphy revealed ischemia in the lateral wall of the left ventricle. There were multiple calcified aneu- rysms in the proximal part of the coronary arteries, which were all detected on 4-row MDCT (Fig. 1A,B). Although these aneurysms were followed up by echocardiography, intralu- minal patency was impossible to evaluate because of heavy mural calcification. MDCT showed large thrombosis within the giant calcified aneurysm of the coronary arteries. One of the advantages of MDCT over echocardiography is that MDCT can depict intraluminal information within the calci- fied wall.
Fig. 1. Thin-slice maximum intensity projection images of proximal right coronary artery and left coronary artery reveal multiple calcified aneurysms, which were successfully followed up by echocardiography. However, large thrombosis (arrow) within the giant aneurysm was not depicted by echocardiography because of heavy calcification.
Case 2: 20-Yr-Old Male
The disease was diagnosed when the patient was admitted to our hospital suffering a high temperature at 6 yr of age. He was treated with aspirin and dipyridamole, being discharged from hospital after 38 d. CAG, performed at the age of 14, showed LCx stenosis and calcification of the RCA. The patient was followed up with treatment of aspirin and dipyridamole. At the age of 18, he underwent further angiography, which showed LCx stenosis and RCA segment 2 calcified aneurysm. Sixteen-
row cardiac MDCT was performed on an out-patient basis in order to evaluate the potential lesions in the coronary arteries.
Cardiac CT confirmed all the abnormalities detected by CAG and verified no new development (Figs. 2 and 3).
Case 3: 21-Yr-Old Female
The disease was diagnosed when the patient was 2 yr of age, when she was admitted to our hospital with a high temperature.
She was discharged from the hospital after 48 d treatment with aspirin and dipyridamole. Echocardiography delineated RCA Fig. 2. Volume-rendered image of multidetector-row CT delineates
heavily calcified aneurysm in segment 2, which was beyond the scope of ultrasound.
Fig. 3. Volume-rendered image shows obstruction in left circumflex coronary artery (arrow).
and LCA aneurysms, which were also detected in CAG per- formed at the ages of 3, 4, 6, and 7. At the age of 10, she underwent further angiography, which showed giant aneurysms in segment 1, segments 2–3, and segments 5–6, small aneurysm in segment 11, and calcification in segments 2–3 and segment 5. The patient was followed up with treatment of aspirin, dipy- ridamole, ticlopidine HCl, and ubidecarenone. At the age of 19, pharmacological stress electrocardiography showed ST-T changes in II, III, aVF, but no ischemia detected on thallium-
201 myocardial perfusion scintigraphy. Echocardiography revealed a giant aneurysm of the distal RCA and calcification of the left main trunk. Cardiac CT on 16-row MDCT was per- formed on an out-patient basis in order to evaluate the potential lesions in the coronary arteries. Cardiac CT confirmed all the abnormalities detected by CAG (Fig. 4A). Furthermore, intra- mural thrombosis in calcified giant aneurysms and small calci- fications in LCx, which were not evaluated by CAG, were also clearly delineated (Figs. 5A,B and 6A).
Fig. 5. Automated segmentations of right coronary (A) and left anterior descending artery (B) show mural calcification and intraluminal thrombosis in giant aneurysm, which are suitable for quantitative assessment of vessel diameters and stenosis degree. There is a focal area of calcification in the proximal left circumflex, which is in normal caliber (arrow). Findings are in keeping with regressed aneurysm. Such lesions carry the potential risk to develop luminal stenosis, and therefore careful and close follow-up is required. Multidetector-row CT is able to detect small calcifications, which cannot be shown by coronary angiography.
Fig. 4. Volume-rendered images of multidetector-row CT clearly delin- eate giant aneurysm in segment 1, calcified giant aneurysm in segments 2 and 6.
SUMMARY
MDCT enables evaluation of coronary arteries, which can- not be reached by echocardiography, such as areas behind calcification and the distal part of coronary arteries. MDCT is considered to be highly efficient in the delineation of abnor- malities in coronary arteries with Kawasaki disease.
Coronary artery bypass grafting using internal thoracic and gastroepiploic arteries is increasing in Japan and the United States, because of the long patency of arterial grafts. The actu- arial graft patency rate for arterial grafts has been reported as 77.1% ± 1.1% (27). Several types of catheter intervention have also been performed in the management of coronary stenosis caused by Kawasaki disease (28,29). Therefore, MDCT is also thought to be a promising non-invasive modal- ity for the assessment of the patency of bypass grafts or coronary stenosis after interventional treatment instead of conventional CAG.
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