Coronary artery outcomes among children with Kawasaki disease in the United States and Japan
Introduction
In the era before the use of intravenous immunoglobulin (IVIG) to treat children with Kawasaki disease (KD), aneurysm rates of approximately 25% were noted both in Japan and the U.S. [1], [2], [3]. KD is now the most important cause of acquired heart disease in children in the developed world and more than 60 countries in Asia, the Middle East, the U.S., Africa, and Europe have reported KD cases [4], [5], [6]. Reported rates of coronary artery (CA) aneurysms vary widely among KD patients from different countries [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. Currently, studies from the U.S. report an aneurysm rate of approximately 4.0–5.0% [7], [17], while rates for Japan are reported to be on the order of 1.0% [9]. To clarify whether this is a problem of semantics (different definitions of aneurysms), a real difference stemming from different clinical practices (timing of echocardiograms or timing of IVIG administration), or differences in host genetics, we conducted a comparative study among two centers in the U.S. and three centers in Japan over the same time period and used the internal diameter of the coronary artery normalized for body surface area (Z-score) as a standardized assessment tool to compare outcomes.
Section snippets
Patient population
Patients with KD included in this study met the case definitions of the American Heart Association (AHA) for the U.S. sites (Rady Children's Hospital San Diego and Boston Children's Hospital) or the Japanese Circulation Society (JCS) for the Japanese sites (Toho University Omori Medical Center, Kitasato University Hospital, and Juntendo University Urayasu Hospital; Table 1) [18], [19]. The records of unselected, consecutive KD patients treated at the five participating centers during the 4-year
Study population characteristics
A total of 1082 subjects were included with 568 from the U.S. and 514 from Japan (Table 2). U.S. subjects were older, were treated on average one day later, and were more likely to be treated after Illness Day 10 as compared to Japanese subjects (p < 0.001 for all comparisons). Japanese subjects were more likely to be classified as clinically incomplete cases (p < 0.001) and were more likely to receive additional infusions of IVIG (p = 0.03).
CA outcomes
The median BSA calculated by either the Du Bois or Haycock
Discussion
This is the first study to directly compare CA outcomes in Japanese and American KD patients using standardized definitions across populations. The median Z-max was significantly higher for Japanese subjects using the Dallaire Z-score equation. When analyzed as a categorical variable, there was no difference in the rate of patients with Z-max scores ≥ 5.0 or ≥ 10.0 using this definition. A higher percentage of Japanese children were classified as having at least one coronary artery segment with a
Acknowledgment of grant support
This work supported in part by grants from the National Institutes of Health, National Heart, Lung, and Blood Institute HL69413 and 108460 awarded to JCB and a Japan Foundation for Pediatric Research grant awarded to SO.
References (34)
- et al.
Kawasaki syndrome
Lancet
(2004) - et al.
Nationwide survey of Kawasaki disease and acute rheumatic fever
J Pediatr
(1991) - et al.
Predictors of coronary artery visualization in Kawasaki disease
J Am Soc Echocardiogr
(2011) - et al.
Predictors of body surface area
J Clin Anesth
(1992) - et al.
Geometric method for measuring body surface area: a height-weight formula validated in infants, children, and adults
J Pediatr
(1978) - et al.
New equations and a critical appraisal of coronary artery Z scores in healthy children
J Am Soc Echocardiogr
(2011) - et al.
Coronary artery dimensions may be misclassified as normal in Kawasaki disease
J Pediatr
(1998) - et al.
The treatment of Kawasaki syndrome with intravenous gamma globulin
N Engl J Med
(1986) - et al.
Long-term consequences of Kawasaki disease. A 10- to 21-year follow-up study of 594 patients
Circulation
(1996) - et al.
Coronary arterial lesions of Kawasaki disease: cardiac catheterization findings of 1100 cases
Pediatr Cardiol
(1986)