Mamoru Ayusawa

Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition)

Abstract  Diagnostic guidelines for Kawasaki Disease was revised to meet the present situation in 2002. This issue intends to explain new guidelines and their backgrounds. Major alterations are interpretation of cases with 4 or fewer febrile days shortened by early intravenous immunoglobulin treatment, and the clinical importance of atypical (incomplete, or suspected) cases.

Dobutamine stress echocardiography for detection of coronary artery stenosis in children with Kawasaki disease

OBJECTIVES This study was designed to assess the feasibility and diagnostic accuracy of dobutamine stress echocardiography for detection of coronary artery stenosis in children with Kawasaki disease. BACKGROUND Dobutamine stress echocardiography is valuable as an alternative test for detection of coronary artery disease in adult patients; however, its usefulness for children has been demonstrated only in limited cases. METHODS Dobutamine stress echocardiography (up to 30 microgram/kg body weight per min) was performed in 50 patients at the convalescent stage of Kawasaki disease, including 26 patients with coronary sequelae documented by previous coronary angiography (sequelae group, 3 to 15 years old) and 24 patients with normal coronary arteries documented by echocardiography (normal group, 7 to 16 years old), who underwent quantitative coronary angiography on a separate day. Left ventricular regional wall motion divided into 16 segments was assessed in relation to the extent of coronary artery disease. A positive test response was defined as a new or worsened wall motion abnormalities. RESULTS Significant coronary artery disease (> or = 50% diameter stenosis of major vessels) was present in 21 patients in the sequelae group. There was no significant difference in the maximal dose of dobutamine between the sequelae and normal groups ([mean +/- SD] 22.4 +/- 5.1 vs. 24.2 +/- 2.5 microgram/kg per min). Heart rate and systolic blood pressure were significantly increased (p < 0.01) at maximal dose of dobutamine compared with values at rest in both groups; consequently, the rate-pressure product exceeded 20,000 in 20 (40%) of the 50 patients during dobutamine infusion. Ten patients had self-limiting side effects; however, there were no serious complications from stress-induced ischemia. New wall motion abnormalities corresponding to the extent of coronary artery disease were detected in 19 of 21 patients in the sequelae group, whereas no wall motion abnormalities were detected in the normal group. Thus, the sensitivity and specificity of dobutamine stress echocardiography for the detection of coronary artery disease were 90% and 100%, respectively. CONCLUSIONS We conclude that dobutamine stress echocardiography is a safe and accurate diagnostic method for detection of coronary artery stenosis in Kawasaki disease. Moreover, this is a possible alternative method for patients unable to exercise adequately, even if they are small children.

Guidelines for diagnosis and management of cardiovascular sequelae in Kawasaki disease

Over 35 years have elapsed since the first case of Kawasaki disease was described in 1967. 1 As they grow older, many patients with a history of Kawasaki disease are treated in departments of internal medicine rather than in pediatric departments. This disease has been extensively studied throughout the world, and many reports have been published on its etiology and cardiovascular sequelae. While the causes of Kawasaki disease unfortunately remain unknown, its cardiovascular sequelae have been intensively studied, contributing to the establishment of their pathology, natural history, diagnosis, and treatment. This provided the impetus for the Japanese Circulation Society to prepare a set of guidelines. The latest guidelines for the diagnosis of Kawasaki disease, as revised in 2002, are shown in Table 1. These are used to diagnose the disease in its acute phase. The diagnostic guidelines may be useful in adults with an unknown history of Kawasaki disease when the illness is suspected from the morphology of any coronary artery aneurysms. In preparing the present guidelines for the cardiovascular sequelae of Kawasaki disease, the first issue addressed was the classification of the size and severity of coronary artery aneurysms using standardized criteria. The consensus criteria shown in Table 2 were prepared according to the conventional classification and the opinions of specialists.

Endogenous nitric oxide and endothelin-1 in persistent pulmonary hypertension of the newborn

Abstract We studied changes in endogenous nitric oxide (NO) synthesis and endothelin-1 (ET-1) production in infants with persistent pulmonary hypertension of the newborn (PPHN). We determined concentrations of serum NO metabolites, i.e., nitrites and nitrates (NOx), and of plasma ET-1 in five infants with PPHN (PPHN group) and in 25 healthy full-term neonates (control group). In both groups, serum NOx concentrations increased over time and plasma ET-1 concentrations decreased with age. The differences in serum NOx concentrations between groups were not significant at <12 h and 24 h of age; however, they were significantly higher in the PPHN group than in the control group at 5 days of age. The differences in plasma ET-1 concentrations between groups were not significant at 5 days of age, but were significantly higher in the PPHN group than in the control group at <12 h and 24 h of age. Conclusion Limited endogenous nitric oxide synthesis and elevated endogenous endothelin-1 production during the first few days of life may contribute to pulmonary hypertension in infants with persistent pulmonary hypertension of the newborn.

Nitric Oxide and Endothelin 1 during Postnatal Life

Nitric oxide (NO) is a potent vasodilator produced by endothelial cells. Endothelin 1 (ET-1), another agent made by endothelial cells, is the most potent vasoconstrictor known to date. Endogenous NO and ET-1 may play a part in the normal physiological pulmonary vascular changes during the postnatal period. However, the changes of NO and ET-1 in healthy neonates have not been defined. We determined serum NO metabolites, i.e., nitrites and nitrates, and plasma ET-1 in 19 healthy neonates at birth (cord blood) and at ages 5 and 30 days. The sums of serum nitrite and nitrate (NOx) levels were 27.5 +/- 12.8, 53.8 +/- 14.2, and 38.3 +/- 13.2 mumol/l at birth, age 5 days, and age 30 days, respectively. The plasma ET-1 concentrations were 3.9 +/- 1.6, 1.1 +/- 0.2, and 1.1 +/- 0.2 x 10(6) mumol/l at birth, age 5 days, and age 30 days, respectively. These changes in healthy neonates suggest the presence of active physiological roles for NO and ET-1 in circulatory adaptation to extra-uterine life.

External validation of a risk score to predict intravenous immunoglobulin resistance in patients with kawasaki disease.

Background: We previously developed a new risk score to predict intravenous immunoglobulin (IVIG) resistance in Kawasaki disease. However, the IVIG dosage used in that study (1 g/kg/d for 2 consecutive days) differs from the single infusion of 2 g/kg recommended in the United States and elsewhere. Our aim was to assess the validity and applicability of our risk score in patients treated with a single infusion. Methods: We used a database of 1626 patients with Kawasaki disease given initial IVIG treatment at a dose of 1 g/kg/d for 2 consecutive days (n = 990; IVIG- 1 g/kg × 2) or 2 g/kg/d for 1 day (n = 636; IVIG- 2 g/kg × 1) across 17 hospitals in Japan. Patients received the total IVIG dose within 36 hours in IVIG- 1 g/kg × 2 and 24 hours in IVIG- 2 g/kg × 1. We stratified the patients according to a risk scoring system developed to predict IVIG unresponsiveness, based on scores of ≥5 points. We compared the accuracy of prediction between the 2 groups using receiver operating characteristic analysis. Results: Baseline characteristics and clinical outcomes were similar between both groups. The areas under the receiver operating characteristic curve in IVIG- 2 g/kg × 1 were similar to those of IVIG- 1 g/kg × 2. Using a cut-off risk score of ≥5 points, we could identify IVIG resistance in terms of coronary artery abnormalities within 1 month and coronary artery abnormalities at 1 month with equivalent sensitivity and specificity in both groups. Conclusion: Our risk score can be used to predict IVIG unresponsiveness to a regimen based on a single infusion of 2 g/kg IVIG.

Characteristics of earlier atherosclerotic involvement in adolescent patients with Kawasaki disease and coronary artery lesions: Significance of gray scale median on B-mode ultrasound

OBJECTIVE To test the hypothesis that textural changes in the carotid intima-media complex (IMC) detected by B-mode ultrasound are associated with the difference of remodeling process in earlier atherosclerotic involvement in patients with Kawasaki disease (KD) and coronary artery lesions (CALs). METHODS Eighteen patients with KD and CALs (mean age 17.2 years), 17 patients with heterozygous familial hypercholesterolemia (FH) (mean age 16.9 years) and 15 age-matched healthy controls (Cont) were assessed and compared for carotid intima-media thickness (CIMT), elastic property (E(p)), and first- and second-order statistics. RESULTS KD showed significantly higher gray scale median (GSM) than FH and Cont. KD and FH showed significantly higher CIMT, entropy and lower angular second moment than Cont, but no significant difference was found between KD and FH. CONCLUSION Higher GSM in KD may indicate alteration of tissue components and heterogeneity of IMC, suggesting the development of arteriosclerotic vascular remodeling after vasculitis. This is distinct from that of atherosclerosis with lower GSM often observed in FH.

Measurement of Coronary Flow Reserve in Children by Transthoracic Doppler Echocardiography

Noninvasive measurement of coronary flow reserve was performed by transthoracic color Doppler echocardiography in 28 children with Kawasaki disease.

Mechanical circulatory support for fulminant myocarditis

PurposeFulminant myocarditis is potentially fatal because it progresses rapidly into cardiogenic shock; thus, immediate and appropriate treatment is essential. Mechanical circulatory support (MCS) is an important part of treatment for fulminant myocarditis. We review our experience of treating fulminant myocarditis with MCS.MethodsWe used MCS with veno-arterial bypass (VAB) to treat seven patients with fulminant myocarditis. Five of these patients were younger than 18 years old. The mean time from arriving at our institution to the initiation of MCS was 15.9 ± 22.6 h. MCS was initiated within 18 h in six patients.ResultsThe mean assist time of MCS was 70.9 ± 35.0 h and six patients were weaned successfully (weaning rate: 85.7%). The remaining patient required support with VAB for 132 h, and a left ventricular assist device was applied. All seven patients were weaned off MCS and discharged.ConclusionsSince severe and rapid hemodynamic compromise is typical of fulminant myocarditis, an immediate decision must be made about whether to initiate MCS. We attribute the excellent results and favorable long-term prognosis of our patients to the early initiation of MCS.

Non-invasive measurement of coronary flow reserve in children with Kawasaki disease

Objective: To investigate whether transthoracic Doppler echocardiography (TTE) can reliably measure the coronary flow reserve in the left anterior descending coronary artery in children with Kawasaki disease. Design: Coronary flow velocity in the distal left anterior descending coronary artery was measured by TTE and was compared with that obtained by intracoronary Doppler guide wire. The ratio of maximum hyperaemia (intravenous administration of adenosine triphosphate, 160 μg/kg/min) to baseline peak (mean) diastolic coronary flow velocity in the distal artery was used as an estimate of coronary flow reserve. Setting: University hospital. Patients: 10 patients with significant left anterior descending coronary stenosis (> 70% diameter stenosis) (group A) in the proximal or middle portion of the artery and 14 patients (group B) without significant stenosis, all with Kawasaki disease documented by previous coronary angiography. Results: The reduced hyperaemic coronary flow velocity in group A compared with group B resulted in a markedly lower coronary flow reserve, derived from both peak diastolic velocity and mean diastolic velocity by either technique of investigation. Multivariate analysis identified the best predictor of left anterior descending coronary artery stenosis to be a coronary flow reserve of ≤ 2.2, derived from mean diastolic flow velocity measured using TTE (sensitivity 90%, specificity 100%, accuracy 96%). A good correlation was found between diastolic velocity derived values for coronary flow reserve measured using both TTE and Doppler guide wire (r = 0.92, p = 0.0001). Conclusions: Coronary flow reserve in the distal left anterior descending coronary artery can be accurately measured using TTE without any intravascular instrumentation in children with Kawasaki disease.