Kawasaki disease (KD) is an acute, self-limiting febrile illness of unknown cause that affects the coronary arteries, predominantly occurring in children aged ≤5 years. KD was first described by Kawasaki in 1967¹⁾ and is now known as the most common cause of acquired heart disease in children in developed countries²⁾. The appropriate initiation of treatment with intravenous immunoglobulin reduces the incidence of coronary artery aneurysms from 25% to 4%^3,4,5,6).

A quantitative assessment of the dimensions of the coronary artery using echocardiography is an important practice in the management of patients with KD. The criteria for coronary artery aneurysm, set by the Japanese Ministry of Health and Welfare in 1984, was a maximum internal diameter of ≥3 mm in children aged <5 years and ≥4 mm in children aged ≥5 years, a segment 1.5 times greater than the adjacent segment, and the presence of luminal irregularity⁷⁾. Until recently, these criteria were widely used as they were easy to memorize and use. However, an underestimation of the incidence of coronary arterial lesions and an inability to reflect children's body growth in the application of these criteria have been pointed out⁸⁾. A standardized score (z score) for assessing cardiovascular structures has been developed for use in pediatric clinical environments as children undergo rapid changes in their physical development with resultant variations in their body size⁹⁾. Several coronary artery z score models have been subsequently proposed^{8,10,11,12,13,14,15)}; a relatively large number of subjects was included, and nonlinear regression methods were adopted in four of models^12,13,14,15). In a recently published practice guideline by the American Heart Association, the classification of coronary arterial lesions is based on the z score of coronary artery diameter²⁾. The previously reported z score model for Korean children has two major limitations: firstly, the number of subjects included in the study for the model was too small and secondly, a linear regression was adopted for model fitting of the body surface area¹⁶⁾. The z score model by Kobayashi et al.¹⁵⁾, which was derived from the lambda-mu-sigma method in 3,851 Japanese children, holds promise for use in Korean children due to its large sample size and the racial similarity between the Japanese and Korean populations.

In this study, an investigation of the statistical properties of 4 previously developed pediatric coronary artery z score models, including the Japanese model, was performed in relation to 181 healthy Korean children. We expected the results of this investigation to present useful information on the selection of z score models in clinical practice in Korea.

One hundred eighty-one children were included in the study, 47% of whom were male (Table 1). The age of subjects was median 2.34 years (range, 1 month to 15 years; Fig. 1). The weight of the subjects was median 12.6 kg (range, 2.9–73.9 kg) and the height was median 89.0 cm (range, 48.7–176.6 cm). The body surface area was median 0.559 cm² (range, 0.201–1.909 cm²). The median diameter of LMCA, LAD, and RCA was 2.13 mm (range, 1.35–4.01 mm), 1.65 mm (range, 1.10–3.26 mm), and 1.60 mm (range, 0.82–3.65 mm), respectively (Table 1).

In this study, the descriptive statistical analyses of coronary artery diameter z scores in 181 normal children were performed using four frequently used z score models (Table 5)^12,13,14,15). As all models are designed to represent a normal population, we expected that the calculated z scores for healthy children would also follow a normal distribution. The Kolmogorov-Smirnov test showed P≥0.050 in three coronary arteries in all 4 models, implying the statistical feasibility of normal distribution. Therefore, it was consequently estimated that the four z score models would be distributed normally, which justifies the application of these models to Korean pediatric populations.

We additionally expected that the mean value of the z score should converge to zero since the subjects were normal healthy children. However, the mean z score value of the 3 coronary arteries was significantly different from zero in each of the four models, except for one of the LADs in the Japanese model. The limited number of subjects in this study could be one of causes. Another explanation for this difference could be the subtle differences in the measuring points. In this study, the mean z score of the RCA was consistently less than zero in all models, which implies that the measured RCA diameters were smaller than the reference values of the z score models. It is reported in the z score model reference papers that the RCA measurements were obtained 2–5 mm distal to its origin in the parasternal short-axis view^13,14,15). In this study, the RCA segment distal to the conal branch was measured in a case with a visible origination of the conal branch to avoid an exaggerated measurement on the branching point. In addition, the measurement point was more distal to 5 mm from the origin of the RCA in some of such cases. As a result, the RCA diameters in this study would have been smaller accordingly. We think that more precise instructions are needed for an accurate and reproducible measurement of the RCA proximal diameter on the issue of the conal branch.

Among the four z score models, the Dallaire and Japanese models were more favorably recommended for use in recent American Heart Association guidelines because they included a relatively larger number of subjects and provide normative data on the left circumflex branch²⁾. Incidentally, the percentage of subjects with an extreme z score of the LMCA appears to be higher in the Dallaire and Japanese models in this study than the expected level under normal distribution. This higher percentage could be due to anatomic variation in several cases, which can be seen in the histograms for the LMCA (Fig. 3). The positive skewness and kurtosis in the distribution of the LMCA z score would not impact on the higher percentage of subjects with extreme z scores of the LMCA. It is well known that anatomic variations are frequent in the LMCA²⁾. Additionally, caution in the interpretation of the LMCA z score was also recommended in recent guideline²⁾. For the other branches of coronary arteries, all four z score models could reasonably be used for the evaluation of vascular dilatation.

The relatively small number of subjects is a limitation of this study.

In conclusion, all 4 models showed statistical feasibility of normal distribution. More precise instructions are needed for RCA measurement. A higher percentage of extreme z scores of the LMCA is compatible with a commonsense understanding of anatomic variations of the LMCA.