Nobutaka Noto

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.

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.

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.

Detection of myocardial contractile reserve by low-dose dobutamine quantitative gated single-photon emission computed tomography in patients with Kawasaki disease and severe coronary artery lesions

We studied 24 patients with severe coronary artery lesions to assess myocardial perfusion and left ventricular contractile reserve simultaneously using low-dose dobutamine quantitative electrocardiographically gated single-photon emission computed tomography in patients with Kawasaki disease. Low-dose dobutamine infusion was started after an injection of technetium-99m tetrofosmin at rest. Myocardial contractile reserve was evaluated using the post-stress and low-dose dobutamine images, and myocardial perfusion was evaluated using the stress and rest images. Quantitative electrocardiographically gated single-photon emission computed tomography during low-dose dobutamine infusion is a useful and safe method for the combined evaluation of myocardial contractile reserve and myocardial perfusion.

Relationship between fat distribution and lipid and apolipoprotein profiles in young teenagers

The influence of obesity and fat distribution on serum levels of lipoprotein and apolipoprotein was investigated in 294 Japanese junior high school children (12‐13 years of age). Serum levels of low‐density lipoprotein cholesterol (LDLC) (P= 0.013), triglycerides (TG) (P= 0.0006), and apolipoprotein B (apoB) (P= 0.003), and the apoB/A‐I ratio (P= 0.005) were significantly higher and serum levels of high‐density lipoprotein cholesterol (HDLC) (P= 0.00003) and apoA‐1(P = 0.003) were significantly lower in obese boys than in non‐obese boys. The serum levels of TG (P = 0.013) and the apoB/A‐1 ratio (P= 0.011) were significantly higher and the serum levels of HDLC (P= 0.004) was significantly lower in obese girls than in non‐obese girls. The LDLC/apoB ratio was lower in obese girls than in non‐obese girls (P= 0.03). Obesity ( 20% of ideal weight) was strongly correlated with the serum levels of lipids and apolipoproteins in boys; this relationship was less clear in girls. The degree of obesity and the body mass index (BMI) were more strongly correlated with serum levels of lipids and apolipoproteins in boys than in girls. In boys, atherogenic‐lipoproteins and apolipoproteins, such as LDLC and apoB, showed a stronger correlation with the thickness of the triceps skinfold, while in girls the anti‐atherogenic lipoproteins and apolipoproteins, such as HDLC and apoA‐1, showed a stronger correlation with both the triceps and the subscapular skinfold thicknesses. In girls the relationships between the BMI and the degree of obesity and the thickness of the subscapular skinfold (S) thickness were similar to the relationships between those parameters and the triceps skinfold (T) thickness. In boys, these parameters showed a stronger correlation with the subscapular skinfold thickness than with the triceps skinfold thickness. The correlation coefficients for the relationships between skinfold thickness and lipid and apolipoprotein levels were similar to the coefficients for the relationships between skinfold thicknesses and the severity of obesity and the BMI. The distribution of central‐type fat accumulation, which is indicated by the thickness of the subscapular skinfold, the S/T ratio and S‐T value, was inversely correlated with the HDLC level in both boys and girls. The degree of obesity was strongly correlated with the atherogenic lipoprotein profile in boys, in part because the subscapular skinfold thickness was strongly correlated with the degree of obesity and the BMI. In girls, the correlations between indices of central‐type obesity and atherogenic lipid and apolipoprotein profiles were stronger than in boys. These data suggest that childhood obesity may be an early cardiovascular risk factor.

Impact of persistent left ventricular regional wall motion abnormalities in childhood cancer survivors after anthracycline therapy: Assessment of global left ventricular myocardial performance by 3D speckle-tracking echocardiography

AIMS To identify left ventricular (LV) mechanical impairment by 3D speckle-tracking echocardiography (3DSTE) in long-term childhood cancer survivors after anthracycline therapy with or without persistent LV regional diastolic wall motion abnormalities (WMA) and a preserved LV ejection fraction (EF >53%). METHODS AND RESULTS Thirty-two patients (median: 14.6 years) and 12 age-matched controls were studied. The patients were divided into two groups according to the existence of WMA: Group 1 (with WMA: n=14), Group 2 (without WMA: n=18). 3DSTE was performed to assess LV global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), global area strain (GAS), LV torsion, LV end-diastolic volume (LVEDV), and LV end-systolic volume (LVESV). LV systolic dyssynchrony index (SDI) was calculated as the percentage of the standard deviation of time to peak strain of the 16 segments divided by the RR interval. There was no significant difference in LVEDV, LVESV, GLS, torsion, or SDI derived from LS, CS, or AS among the 3 groups. In contrast, there were significant differences in GRS, GCS, and GAS, and SDI derived from RS among the 3 groups. Compared with group 2, group 1 had significantly reduced GRS (p<0.001), GCS (p<0.01), GAS (p<0.01), and greater SDI derived from GRS (p<0.01). Moreover, the existence of WMA was correlated with GRS (p<0.001), SDI derived from GRS (p<0.001), and LVEF (p=0.036). Multiple linear regression analysis identified GRS as a significant determinant of the existence of WMA (β=0.751, p=0.001). CONCLUSION Childhood cancer survivors with persistent LV regional WMA show a reduced LV myocardial performance compared with those without WMA, despite a preserved LVEF.

Estimation of “Selective” Intravenous Gamma Globulin Treatment Indicated by Harada Score

Harada score, which was originally constructed as a guideline for indication of intravenous gamma globulin (IVGG) in research group of Kawasaki disease promoted by the Ministry of Health (Kouseishou), had been applied to consecutive 258 cases of Kawasaki disease between 1989 and 1998. Each item of score are regarded as positive when patient is male, 12-month-old or younger, white blood cell count is 12,000/mm3 or more, platelet count is less than 350,000/mm4C-reactive protein is 4.0mg/dl or more, hematocrit is less than 35%, serum albumin is less than 3.5g/dl. Concerning to these items, 203 cases (78.7%) fulfilled 4 or more items and were treated with IVGG. Among them, coronary artery lesion (CAL) developed in 28 cases (13.8%) at 30th day after onset and remained after 1 year in 19 cases (7.4%). Giant aneurysm larger than 8mm in diameter developed in 3 cases (1.5%). Fifty-five cases fulfilled 3 or fewer items and were not treated with IVGG. CAL developed in 2 cases (3.6%) at 30th day and both of them regressed to discontinue medication until 1 year after onset. Frequency of blood examinations while patient is in hospital were done every 3.13±0.87 days in cases during 3 years from 1986 to 1988 before Harada score was evaluated, while during 10 years of this study examinations were done every 3.06±0.46 days in cases that IVGG was indicated, and 2.81±0.68 days in cases that IVGG was not indicated. Harada score has utility with 93.3% and 100% of sensitivity at 30th day and over 1 year respectively, for selection of cases which IVGG is absolutely necessary for prevention of CAL. Though frequency of blood tests tends to increase, statistics concerning to it was not significant.

Recent updates on echocardiography and ultrasound for Kawasaki disease: beyond the coronary artery

Kawasaki disease (KD) is a systemic vasculitis with a predilection for damage to the coronary arteries. In the acute phase, clinical decision making for KD relies on the measurements of the coronary z-score obtained by 2-dimensional echocardiography (2DE). In the convalescent phase, KD patients with coronary artery abnormalities (CAAs) eventually show arteriosclerotic vascular remodeling characterized by marked intimal proliferation and neoangiogenesis after KD vasculitis, which often induces myocardial ischemia. To date, several well-established surrogate markers including dobutamine stress echocardiography (DSE), the carotid intima-media thickness (CIMT) and flow-mediated dilatation (FMD), have been made available for risk assessment and the prediction of cardiovascular disease (CVD) in KD patients. Additionally, the use of carotid contrast-enhanced ultrasonography (CEUS), has enabled the visualization and quantification of the adventitial vasa vasorum (VV) network, assessing active vascular remodeling at remote arterial sites in KD patients with CAAs. However, there was no evidence of major vascular structural changes in KD patients in whom CAAs had never been detected. Thus, assessment of multiple modalities using 2DE may provide direct information not only on the vascular health but also on the stratification of the risk of CVD in KD patients with CAAs.

Premature Atherosclerosis Long After Kawasaki Disease

Kawasaki disease (KD) is a systemic vasculitis of unknown etiology in infants and children. First described in Japan in 1967, KD has been described worldwide among children of all races and ethnicities (Kawasaki, 1967). More than 4000 hospitalizations associated with KD were reported in 2000 and KD is the leading cause of acquired heart disease in childhood in the United State (Taubert et al., 1991). In Japan, the national survey of KD has performed every 2 years since 1970. From the most recent 20th survey dealt with the years 2007 and 2008, the number of new cases of KD in those years was 11,581 and 11,756, respectively. As of 2008, the total number of patients since 1970 was 249,019 (Nakamura et al., 2010). Therefore, patients diagnosed with KD in the sixties and seventies have already reached adulthood. The increased incidence of young adults who experience KD during childhood has been accompanied by a new problem of an association between post-KD lesions and atherosclerosis.