Background
Coronary artery wall echogenicity increases on echocardiograms during the acute phase of Kawasaki disease (KD). According to this background, echogenicity of the coronary artery wall in patients with KD is quantified by using integrated backscatter (IB) analysis.
Methods
IB analysis is a quantitative method for evaluating echogenicity. We examined the value of IB in the wall of the left anterior descending coronary artery and compared it with that in adjacent intracardiac blood as a measure of background. The difference between these values is represented as corrected IB for the coronary artery wall.
Results
Corrected IB for the coronary artery wall was higher in patients with KD than in controls (KD with pre-immunoglobulin therapy vs. controls: 27.4 ± 5.3 dB vs. 22.0 ± 3.5 dB, P < .05) and in patients with coronary enlargement after intravenous immunoglobulin (with vs. without coronary enlargement, 29.2 ± 5.2 dB vs. 24.1 ± 5.5 dB, P < .05).
Conclusion
The magnitude of IB from the coronary artery wall reflects the effectiveness of immunoglobulin therapy. Furthermore, this method and its value might be useful to predict the occurrence of coronary enlargement in patients with KD.
The most serious sequela of Kawasaki disease (KD) is coronary enlargement, such as coronary aneurysm. Coronary enlargement may subsequently cause ischemic heart disease or myocardial infarction. The luminal diameters of coronary arteries are often measured using two-dimensional echocardiography, and this method has become the clinical standard for patients with KD. Echogenicity in the coronary artery wall apparently increases during the acute phase of KD according to American Heart Association guidelines, and it is considered an important factor among patients with atypical KD. However, to estimate the echogenicity of the coronary artery wall is somewhat difficult. Integrated backscatter (IB) analysis is a quantitative method for evaluating echogenicity, and it is applied to ultrasonographic assessment of the myocardium, arterial tissues and coronary arterial plaques. The study’s objective was to determine whether coronary echogenicity is different in patients with KD versus controls, to describe the time course of changes in IB during the acute and convalescent phase of KD, and to investigate whether differences in echogenicity might identify patients at increased risk of developing coronary artery changes.
Materials and Methods
We enrolled 27 patients with KD (KD group) who were treated with intravenous immunoglobulin (IVIG) and 15 control patients who were examined by echocardiography for other heart diseases (non-KD group). Sixteen of the 27 patients in the KD group were male and 11 patients were female (mean age, 1.8 ± 1.2 years; range, 2 months to 4 years). The first IVIG treatment improved symptoms in 17 patients, whereas the other 10 patients required additional IVIG treatment ( Table 1 ). The patients’ treating physician decided whether the IVIG protocol was 400 mg/kg/d for 5 days or a bolus of 1 to 2 g/kg over 24 hours. The treatment strategy was considered effective when fever was decreased within 48 hours of the first IVIG. If fever continued for over 48 hours after the first IVIG treatment, then a second IVIG treatment was administered. Coronary enlargement was defined as an inside diameter of the coronary artery of greater than 3 mm determined by echocardiography. Fifteen patients with non-KD conditions (9 male and 6 female; mean age, 1.7 ± 1.2 years) served as controls. Their conditions included ventricular septal defect (n = 5), atrial septal defect (n = 3), peripheral pulmonary artery stenosis, (n = 2), patent ductus arteriosus, (n = 1), Wolff–Parkinson–White syndrome (n = 1), and innocent murmur (n = 3). During evaluation of congenital heart disease among this group, all coronary arteries evaluated by echocardiography appeared normal.
| Coronary enlargement (+) n = 5 | Coronary enlargement (−) (n = 22) | P value | |
|---|---|---|---|
| Age (y) | 1.0 ± 0.6 | 2.1 ± 1.2 | NS |
| Male, n (%) | 3 (60) | 13 (59) | NS |
| Additional IVIG, n (%) | 3 (60) | 7 (32) | NS |
The IB of coronary artery wall tissues was determined using SONOS 5500 or SONOS 7500 echocardiography systems equipped with acoustic densitometers (Royal Philips Electronics, Ams-terdam, The Netherlands) under the following standardized conditions: gain control, 50 dB; dynamic range, 75 dB; and time gain control, medial position with the lowest lateral gain control. IB images during two to three heartbeats were recorded on an optical disk at 30 frames per second, replayed off-line, and frozen when the image was suitable for determining IB, mainly at the end-systolic phase, using a minimal (11 × 11 pixels) elliptical region of interest (ROI) ( Figure 1 ) for the echocardiography system. The value of IB was calculated in the wall of the left anterior descending coronary artery (IB CA ) and the background (IB BG ) at an intracardiac blood adjacent to the target coronary artery. The corrected IB CA value represents the difference between the IB CA and IB BG of the coronary artery wall ( Figure 1 ).
IB was determined in the KD group at three separate times: before the first IVIG (acute phase), within 12 hours of the last IVIG (after IVIG), and at least 30 days after onset of KD (convalescent phase) under approximately identical conditions (set in memory mode) throughout the observation, with respect to depth and location of the ROI.
To assess the reproducibility of the corrected IB CA value, each IB image was stored on an optical disk, and the IB CA and IB BG were determined by 2 separate operators (interobserver measurement variability) and twice in the same frame by a single operator (intraobserver measurement variability).
The results for the KD (in acute phase, after IVIG, and convalescent phase) and non-KD groups are shown as means ± standard deviation. Means between the KD and non-KD groups and between any two subgroups in the KD group were statistically analyzed using an unpaired t test. Changes over time in the KD group were assessed using a paired t test. The reproducibility of inter- and intra-operator IB values was compared using Pearson’s correlation coefficient and Bland–Altman analysis. A P value of less than .05 was considered significant.
All parents provided written, informed consent to their children undergoing additional conventional coronary artery examinations of the IB in the coronary artery wall.
Results
Reproducibility of Measurement of Integrated Backscatter
The correlation coefficient of corrected IB CA values from 23 image files that displayed a distinct coronary artery and the mean difference in inter-operator reproducibility between two operators were 0.64% and 2.3% ± 7.6%, respectively ( Figure 2 ). The correlation coefficient and mean difference in intra-operator reproducibility were 0.80% and 0.7% ± 7.2%, respectively ( Figure 3 ).
Corrected Integrated Backscatter for Coronary Artery Values in Kawasaki Disease versus Non-Kawasaki Disease
Mean corrected IB CA values before and just after IVIG and during the convalescent phase were 27.4 ± 5.3 dB, 25.1 ± 5.7 dB, and 25.2 ± 5.6 dB, respectively, in the KD group, and baseline IB CA was 22.0 ± 3.5 dB (range, 15.6–28.6 dB) in the non-KD group ( Figure 4 ).
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