Circulating Cardiac Troponin I Levels in Kawasaki Disease

In addition to the vascular findings of Kawasaki disease (KD), clinical, electrocardiographic, and/or echocardiographic signs of myocarditis are recognizable in the acute phase of KD in many patients. The mechanism of myocarditis and an association with the development of subsequent coronary artery abnormalities in KD is unknown. Previous studies of serum cardiac troponin I (cTnI) measurements in pediatric populations have suggested a possible utility of measurements in diagnosis and follow-up of KD. We designed a retrospective study to evaluate cTnI measurements during acute KD and to assess the predictive value of cTnI measurements in acute KD for the subsequent development of coronary artery abnormalities. Twenty-nine children were studied. Group 1 consisted of 15 KD patients who developed coronary artery abnormalities as detected by transthoracic echocardiographic evaluation. Group 2 consisted of 14 KD patients with persistently normal coronary artery findings on echocardiograms. A control group consisted of 11 children, none of whom were known to have had clinical findings of KD or myocarditis. The mean cTnI values for all three groups were lower than the values suggestive of cardiac damage: group 1 = 0.11 ± 0.16 ng/ml, group 2 = 0.15 ± 0.34 ng/ml, and control = 0.04 ± 0.08 ng/ml. The current study demonstrates that there is no significant elevation of cTnI in KD patients. Additionally, there is no correlation between cTnI measurements and the finding of myocarditis, as reflected by decreased cardiac function, or the subsequent development of coronary artery abnormalities.     

Cardiac Troponin I in Fulminant Adenovirus Myocarditis Treated with a 24-Hour Infusion of High-Dose Intravenous Immunoglobulin

We report a successful outcome on an acute adenovirus myocarditis treated with a 24-hour high-dose intravenous immunoglobulin (24-HDIVIG) in a 4.5-year-old girl. A postviral etiology of acute myocarditis was assessed on the basis of the polymerase chain reaction technique. Among other early markers of cardiac injury, cardiac isoform of troponin-I (cTnI) was significantly correlated to the left ventricular ejection fraction (r=−0.86, p < 0.0001). Follow-up of cTnI, which might also be correlated to the short-term outcome, allows fast, easy, and noninvasive estimation of response to the aggressive treatment with 24-HDIVIG in acute adenovirus myocarditis in children.     

血清心肌肌钙蛋白I诊断川崎病急性期心肌损伤的临床价值

为探讨血清心肌肌钙蛋白I(cTnI)诊断川崎病(KD)急性期心肌损伤的临床价值。检测KD组(n=40)及对照组(n=23)患儿血清cTnI、肌酸激酶(CK)、肌酸激酶同功酶(CK-MB)、乳酸脱氢酶(LDH)与谷草转氨酶(GOT)浓度。结果显示①KD组与对照组血清CK、LDH、GOT浓度无显著性差别(P＞0.05);而血清cTnI、CK-MB浓度明显高于对照组水平(P＜0.001)。②在诊断KD患儿急性期心肌损伤上cTnI优于CK-MB(P＜0.05),。结果表明cTnI与CK-MB对KD患儿急性期心肌损伤有诊断价值;与CK-MB比较,cTnI具有高特异性、灵敏度。     

Estimation of myocardial damage in Kawasaki disease using antimyosin antibody

In a retrospective study, 121 children with Kawasaki disease (KD) were investigated to determine (i) the incidence of myocardial damage using the antimyosin antibody (AMA) titer; (ii) the differences in the electrocardiograms between the AMA-positive and -negative patients; and (iii) the effect of treatment with intravenous gamma globulin (IVGG) on the AMA. Comparisons were made with 117 normal children (controls). Patients with KD showed a significantly higher mean AMA titer and more patients were positive for AMA than the controls. The AMA titer in the KD group was not related to the presence of coronary artery lesions. Electrocardiograms obtained during the acute and the convalescent stage of KD revealed that patients positive for AMA had a significantly lower voltage of T wave in lead V6 at week four than at week two of illness, whereas patients negative for AMA showed no T wave change after week two. The group treated with IVGG showed a significantly lower AMA titer than that not given IVGG. These observations suggest that myocardial damage occurs in some patients with KD which is unrelated to the presence of coronary artery lesions and that the treatment with IVGG reduces the AMA titer in patients with KD.     

Echocardiographic Evaluation of Systolic and Diastolic Function in Postoperative Coarctation Patients

Postoperative coarctation (CoA) patients are often found to have signs of persistent myocardial dysfunction. M-mode echocardiography was performed to study left ventricular (LV) size, mass, and systolic function and Doppler ultrasonography to study LV filling and flow velocity in the LV outflow tract and aorta in 28 ``healthy' postoperative CoA patients (5–21 years) and 28 age- and sex-matched controls. The early (E) and late (A) diastolic transmitral velocities were significantly higher in the patient group than in the controls (p < 0.05). Other diastolic parameters (isovolumic relaxation time, E/A ratio, and deceleration time of the early diastolic velocity) were similar in the two groups (p= NS). The left atrial diameter, LV wall average, end-diastolic diameter of the LV and LV mass were higher in the patients than controls (p < 0.05). The patients also had a higher stroke volume, cardiac output, and cardiac index than the controls (p < 0.01). The fractional shortening was similar in the two groups (p= NS). Blood flow velocities in both the LV outflow tract and aorta were higher in the patients than the controls (p < 0.0002). We found LV hypertrophy with signs of a hyperdynamic circulation (increased cardiac index and stroke volume) in our patients. An increase in A is associated with LV hypertrophy and seems to be a sensitive marker of diastolic abnormality. The rise in E is paradoxical but has been seen in other studies. The increased blood flow velocity in the LV outflow tract suggests obstruction to LV outflow and increased flow in the descending aorta is due to residual coarctation.     

Clinicopathologic Characteristics of Hypertrophic Cardiomyopathy Detected During Mass Screening for Heart Disease

Between 1981 and 1992 a total of 10 patients with hypertrophic cardiomyopathy (HCM) were detected by mass screening for heart disease in Tokyo's Adachi Ward. Four were first grade elementary school children and six were first grade junior high school adolescents. Two-dimensional echocardiography at the initial evaluation revealed asymmetric septal hypertrophy in four patients, diffuse hypertrophy of the left ventricle in five, and poor left ventricular contractility with wall thinning in one (dilated phase). Three of the five patients with diffuse hypertrophy progressed to asymmetric septal hypertrophy during the average 4-year follow-up period. The degree of septal thickness and the left ventricular wall thickness index were significantly less than in those of young adult controls (12 ± 3 versus 21 ± 9 mm, p < 0.05; and 22 ± 4 versus 28 ± 16 mm, p < 0.05, respectively). Right ventricular endomyocardial biopsy specimens obtained from 9 of the 10 patients showed features typical of HCM (e.g., myocyte hypertrophy with myofibril disarray) in five patients and atypical features (mainly interstitial fibrosis with perivascular cell infiltration) in another four. One patient with dilated phase disease died of congestive heart failure 6 months after the initial evaluation. These results indicate that HCM detected during mass screening is a mild form of the disease and may have atypical pathologic features, such as interstitial fibrosis and perivascular cell infiltration, mimicking the sequela of chronic myocarditis.     

Predictive risk factors for coronary artery abnormalities in Kawasaki disease

Clinical characteristics to predict the development of coronary artery abnormalities (CAA) in Kawasaki disease (KD) were assessed by reviewing medical records of patients diagnosed with KD at Korea University Medical Center from March 2001 to February 2005. Of the 285 patients diagnosed with KD, 19 developed CAA (6.7%). Compared with the CAA(−) group, the CAA(+) group had a longer duration of fever after intravenous gamma-globulin (IVGG) injection (2.4±2.9 vs. 1.5±1.2 days, p=0.008) and higher C-reactive protein (CRP)(12.3±7.8 vs. 8.7±7.1 mg/dL, p=0.038). In particular, the CAA(+) group tended to have more than 7 days of fever before IVGG and more than 3 days of fever after IVGG (26.3 vs. 5.3%, p<0.001; 26.3 vs. 6.4%, p=0.002). When the IVGG responsiveness was defined by the presence of defervescence within 3 days after IVGG, IVGG-non-responders showed a higher incidence of CAA (22.7 vs. 5.3%, p=0.002). Non-responders had a longer duration of fever after IVGG (5.5±1.9 vs. 1.2±0.6 days, p<0.001) and a significantly increased CRP, AST, ALT and total bilirubin. Multivariate regression analysis for CAA showed that the only factor significantly associated with the development of CAA was total fever that lasted for longer than 8 days (OR=4.052, 95% CI=1.151–14.263, p=0.0293). Conclusively, the most important predictor of CAA in KD is total duration of fever longer than 8 days. Early identification of IVGG non-responders and active therapeutic intervention for fever in KD cases might decrease the incidence of CAA.     

Use of Intravenous γ-Globulin for Kawasaki Disease: Effects on Cardiac Sequelae

The administration of intravenous γ-globulin (IVGG) for Kawasaki disease was investigated throughout Japan in 1993 by obtaining information from pediatric departments in 2652 hospitals that had more than 100 beds. Of 11,221 reported patients, 8958 patients (79.8%) received IVGG treatment. Of all the patients to whom IVGG was administered, the most common total dose was 1000 mg/kg (36.3%) followed by 2000 mg/kg (16.9%) and 1200 mg/kg (16.8%). The treatment was started in 53.8% by day 5 of the illness and in 83.7% by day 7. The proportion of those with cardiac sequelae was higher among patients administered >2000 mg/kg or in those started on IVGG on day 9 of their illness or later. The possible reasons are (1) those who were more severely affected were treated with high-dose IVGG earlier; or (2) IVGG does not effectively prevent cardiac sequelae. We concluded that there is a risk of unfavorable effects with IVGG regarding cardiac sequelae when the IVGG dose is >2000 mg/kg or if IVGG is started on day 9 or later. We believe that only a randomized controlled trial, undertaken prospectively, can adequately address the question of the optimal use of IVGG.     

心型脂肪酸结合蛋白在川崎病患儿中的变化及其临床意义

目的：通过测定川崎病（KD）患儿血清心型脂肪酸结合蛋白(h-FABP)水平变化,以探讨h-FABP在反映KD患儿心肌损害中的临床价值。方法：选择40例KD患儿为研究对象,以30例正常儿童为对照组。对KD组及对照组采用酶联免疫吸附法检测血清h-FABP、肌钙蛋白I（cTnI）,同时利用杜邦全自动生化分析仪检测肌酸磷酸激酶同功酶（CK-MB）。并行心脏彩色多普勒(UCG)检测冠状动脉内径,将KD组分为冠状动脉病变（CAL）组和非冠状动脉病变（NCAL）组。结果：KD组血清h-FABP浓度、阳性率与对照组比较差异有显著性（P<0.01）,cTnI浓度及阳性率明显高于对照组(P<0.05),而CK-MB浓度和阳性率与对照组比较差异无显著性（P>0.05）;h-FABP与cTnI阳性率比较差异有显著性（P<0.01）;CAL组和NCAL组血清h FABP浓度对比差异有显著性（P<0.01）。结论：血浆h-FABP、cTnI浓度可作为KD患儿早期心肌损害的生化标志物,而h-FABP具有更高的灵敏度和特异性;血浆h-FABP浓度对川崎病以及川崎病合并冠状动脉病变的早期诊断、指导治疗具有重要的临床意义。     

Plasma Concentrations of Atrial and Brain Natriuretic Peptides and Cyclic Guanosine Monophosphate in Response to Dobutamine Infusion in Patients with Surgically Repaired Tetralogy of Fallot

We examined the plasma concentrations of atrial and brain natriuretic peptides (ANP and BNP) and cyclic guanosine monophosphate (cGMP) during dobutamine infusion and their relationship with hemodynamic parameters in 14 patients with surgically repaired tetralogy of Fallot (TOF). Dobutamine was infused at an initial dose of 5 μg/kg/min and increased by 5 μg/kg/min up to 20 μg/kg/min. The plasma ANP, BNP, and cGMP concentrations were determined before infusion, at the end of each stage, and 15 minutes after discontinuing dobutamine infusion. The plasma concentrations of ANP, BNP, and cGMP were elevated in all patients before dobutamine infusion. The ANP, BNP, and cGMP concentrations decreased in 11 of the 14 patients during dobutamine infusion. In contrast, the plasma ANP and BNP concentrations increased in the remaining 3 patients without a change in the cGMP concentration. The right ventricular pressure and volume were significantly elevated in these patients. The plasma cGMP concentration correlated with the ANP concentration (r= 0.62, p < 0.01) but not the BNP concentration. The plasma ANP concentration during dobutamine infusion correlated with right ventricular systolic pressure (r= 0.71, p < 0.05), mean right atrial pressure (r= 0.29, p < 0.05), and mean pulmonary capillary wedge pressure (r= 0.32, p < 0.05). The BNP concentration correlated with right ventricular volume (r= 0.61, p < 0.05) and systolic pressure (r= 0.46, p < 0.05). In conclusion, rapid changes in ANP, BNP, and cGMP concentrations during dobutamine infusion reflect the changes in atrial and ventricle pressure and volume overload. In surgically repaired TOF, the ANP concentration is affected by right ventricular systolic pressure, right atrial pressure, and pulmonary capillary pressure. Furthermore, the BNP concentration reflects right ventricular pressure and volume overload.     

A Cluster of Fulminant Myocarditis Cases in Children,Baltimore, Maryland, 1997

The true incidence of myocarditis in children is difficult to estimate because many mild cases go undetected. This study describes an unusual cluster of myocarditis cases that occurred in young children living in the greater Baltimore area between May and October 1997. A search of multiple comprehensive databases and interviews with area pediatric cardiologists were conducted to identify unreported cases and determine the background rate of myocarditis in the area. Seven cases of myocarditis were found as well as two with a similar clinical picture and myocardial fibrosis on tissue examination. Six case patients with active myocarditis and one child with fibrosis died. The case children were predominantly black (eight of nine) and male (seven of nine), with no identifiable risk factors. The disease was characterized by a fulminant course with malignant arrhythmias. The greatest number of pediatric myocarditis deaths reported in 1 year prior to 1997 was three. Myocardial tissues were examined using immunohistochemistry, in situ hybridization, and polymerase chain reaction but no etiologic agent was identified. This outbreak is unusual because of both the number of cases and the fulminant course of the disease in this group of children.     

Exercise-Induced Hypertension After Corrective Surgery for Coarctation of the Aorta

The purpose of this investigation was to study exercise-induced hypertension after surgical repair of coarctation of the aorta (CoA). Groups of 27 patients with CoA and 27 healthy control subjects, 6–21 years old, were exercised to exhaustion using the Bruce protocol. Fourteen patients had undergone surgery during the first year of life (group A), and 13 patients had been operated on later (group B). The pulse rate and systolic blood pressures (BP) in the arm and leg were measured before, during, and after exercise to evaluate changes in the BP and the arm/leg BP gradient with exercise. The systolic BP was significantly higher in the patients than in the controls at all stages of the exercise test (p < 0.01), as was the arm/leg BP gradient both before and after exercise (p < 0.01); the latter increased significantly with exercise in the patient group (p < 0.05). We found hypertension to be a more common and severe problem in group B patients, who had higher blood pressures than their controls at rest and during exercise (p < 0.05). Exercise-induced hypertension was also more common in group B (23%) than in group A (7%). We conclude that exercise-induced hypertension and recoarctation are problems in postoperative CoA patients. Moreover, exercise-induced hypertension is more common in patients with CoA operated on after the first year of life.     

Increased nitric oxide production by neutrophils in early stage of Kawasaki disease

Recent observations suggested that nitric oxide (NO) has a role in triggering the early endothelial dysfunction in Kawasaki disease (KD). We investigated the amount of NO in conjunction with reactive oxygen species (ROS) produced by neutrophils in children with acute KD by a newly developed flow cytometric analysis. Forty children with acute KD (n = 14), non-KD febrile disease (n = 14), and afebrile control (n = 12) were enrolled (age, 3 to 88 months). Neutrophils in KD produced significantly higher amount of NO compared to others (p < 0.05). With regard to ROS, significant increase was not only found in KD but also in non-KD febrile children (p < 0.05 and p < 0.01, respectively). In KD patients, the amount of NO produced by neutrophils decreased after immunoglobulin (IVIG) treatment, while there was no significant change in ROS production. The amount of NO in KD patients also correlated well with the days from the onset. One patient who developed coronary arterial lesion showed the highest value of NO. In conclusion, neutrophils in acute KD generate both NO and ROS considerably, while NO production is exclusive in the early stage of KD before IVIG treatment. Abnormal immune system in KD might be characterized by an overproduction of NO, whereas the role of NO in endothelial damage remains to be elucidated.     

重症肺炎患儿心肌肌钙蛋白Ⅰ变化的意义

目的探讨心肌肌钙蛋白I(cTnI)在重症肺炎时的变化及其对心肌损害的诊断价值。方法应用Access全自动微粒子化学免疫分析仪,采用cTnI试剂盒检测47例重症肺炎急性期、25例恢复期血cTnI水平。结果33例急性期重症肺炎患儿血cTnI明显升高,异常率达70.2%,与非重症肺炎组比较有非常显著差异(P<0.01);恢复期11/25例升高,异常率44%,较急性期明显降低(P<0.05),cTnI与心肌损害程度呈显著正相关(r=0.63P<0.01)。结论重症肺炎患儿存在心肌损害,cTnI可作为早期监测心肌受损的指标。     

Percutaneous Transluminal Angioplasty for Stenosis of the Aorta Due to Aortic Arteritis in Children

Percutaneous transluminal balloon angioplasty for stenosis of the aorta due to aortic arteritis was attempted on 45 lesions in 41 children (age range, 4–14 years; mean, 9.9±4.2 years) presenting with symptoms of hypertension, severe congestive heart failure, and lower limb claudication. Balloon dilatation was technically successful in 38 (92.7%) patients for 41 stenotic lesions (91.1%). The mean peak systolic pressure gradient (PSG) decreased from 71.7 ± 23.9 mmHg to 23.2 ± 17.5 mmHg (p < 0.001) and the diameter of the stenosed segment increased from 3.3 ± 1.1 mm to 7.5 ± 2.2 mm (p < 0.001) immediately after angioplasty. Patients with short-segment (<3 cm) stenosis had a lower residual gradient (17.9 ± 11.1 mmHg vs 30.5 ± 22.6 mmHg; p < 0.05) and a wider diameter of the aorta (8.8 ± 1.1 mm vs 7.5 ± 2.2 mm; p < 0.02) compared to patients with long-segment (≥3 cm) stenosis. Four patients required stent implantation; 2 for flow-limiting dissection, 1 for failure to reduce PSG by >50%, and 1 for recurrent restenosis. There was marked hemodynamic and angiographic improvement in these 4 patients. Hemodynamic and angiographic restudy in 21 of the 41 patients at mean follow-up period of 6.2 ± 4.2 months (range, 3–24 months) showed restenosis in 4 (19%) patients. Restenosis was more common in patients with long-segment stenosis than those with short-segment stenosis (30% vs 9.1%). Late restudy in 8 patients, done at 3–7 years after first restudy, showed no recurrence of aortic narrowing. On clinical follow-up of 38 patients for a mean of 58.8 ± 36.0 months (range, 8–146 months) there was marked improvement in symptoms. Hypertension was cured in 11 (29%), improved in 24 (63%), and persisted in 3 (8%). Six patients with associated severe renal artery stenosis showed further improvement in hypertension after successful renal angioplasty. Severe congestive heart failure improved in 21 (95.4%) of 22 patients. Mean left ventricular ejection fraction improved from 0.32 ± 0.08 to 0.48 ± 0.10 (p < 0.001) at a mean follow-up of 28.7 ± 8.4 months in these patients. Hemodynamic restudy in 10 of these patients showed improvements in left ventricular end-diastolic pressure from a mean 37 ± 9 mmHg (range, 25–55 mmHg) to 16.4 ± 6.2 mmHg (range, 6–25 mmHg) (p < 0.001). Lower limb claudication improved in all 4 patients. Our results suggest that percutaneous transluminal balloon angioplasty in children is safe and highly effective in relieving stenosis of the aorta due to aortic arteritis, with marked clinical improvement, and should be the treatment of choice particularly for discrete stenosis.     

Responses of Plasma Norepinephrine and Heart Rate During Exercise in Patients After Fontan Operation and Patients with Residual Right Ventricular Outflow Tract Obstruction After Definitive Reconstruction

To determine the exercise responses of patients with congenital heart disease, 20 patients—5 who had undergone a right ventricular outflow tract reconstruction (group R; age, 15 ± 2 years), eight who had undergone a Fontan operation (group F; age, 13 ± 2 years), and seven who had a history of Kawasaki disease (group C; age, 15 ± 1 years)—performed a treadmill exercise test. Patients of group R had a significant residual right ventricular outflow obstruction. Oxygen uptake (VO₂), heart rate (HR), and plasma norepinephrine (NE) concentrations were measured at rest, during warm-up, at ventilatory threshold (VT), and at peak exercise. Exercise capacity was determined as a percentage of the predicted normal peak VO₂ (%pVO₂). The %pVO₂ for groups R and F was 65 ± 10 and 56 ± 11, respectively. Peak HR for groups R and F was 171 ± 4 and 155 ± 5, which were lower than the HR for group C (p < 0.001). Although NE concentrations at rest, during warm-up, and at VT were significantly greater in groups R and F (p < 0.05), there were no significant differences in the NE concentrations at peak exercise. Peak HR correlated with %pVO₂ (p < 0.001). The ratio of the increase in HR to NE from rest to VT was significantly lower in groups R and F than in group C (p < 0.001) and correlated with %pVO₂ (r= 0.80; p < 0.001). These data suggest that sympathetic nervous activity in groups R and F is increased at rest and during mild to moderate exercises, and reduced sinus node sensitivity to NE may be partly responsible for the abnormal HR response during exercise of patients with uncorrected congenital heart disease.     

Correlation of Plasma Adrenomedullin to Myocardial Preservation During Open-Heart Surgery

Adrenomedullin (ADM) is a vasoactive peptide with potent dilatory effects. We studied whether perioperative myocardial injury could be altered by the presence of ADM. Blood samples from 19 children with congenital heart disease undergoing surgical repair were collected at six time points: preoperative, on cardiopulmonary bypass (CPB), and 0, 3, 6, and 12 hours after CPB. Blood levels of ADM (pg/ml) and troponin-I (Tn-I; ng/ml), a specific marker of myocardial injury, were measured. Patients were divided into three groups based on their 12-hour Tn-I levels (I, < 10, n= 6; II, 10–25, n= 6; III, >25, n= 7). Preoperative Tn-I levels were within the normal range for all patients. Preoperative ADM levels in group I (with little or no evidence of myocardial injury) were significantly greater than those of either group II or III (242.7 ± 15.4 vs 83.8 ± 18 and 85.2 ± 5.5, respectively; p≤ 0.0001 for each). The 12-hour ADM levels in group I remained significantly lower than preoperative levels (242.7 ± 15.4 vs 197.4 ± 11.6, p≤ 0.03) but higher than in the other groups. In group III, ADM increased at the 12-hour time point (159.2 ± 6.5, p≤ 0.0001 vs baseline). Higher preoperative ADM levels are associated with lower levels of myocardial injury (as assessed by troponin-I release) during congenital heart surgery.     

Pulmonary Artery Dilation and Right Ventricular Function in Acute Kawasaki Disease

Coronary artery inflammation and aneurysm formation are the most common complications of Kawasaki disease (KD). Valvulitis and myocarditis are also well described and may lead to valvar regurgitation and left ventricular dysfunction. However, functional changes in the right heart have rarely been reported. We noted several acute KD patients with dilated pulmonary arteries (PA) and thus sought to systematically characterize PA size and right-heart function in an unselected cohort of KD patients cared for at a single clinical center. Clinical, laboratory, and echocardiographic data from 143 acute KD subjects were analyzed. PA dilation was documented in 23 subjects (16.1 %); these subjects had higher median right ventricle myocardial performance index (RV MPI), higher ratio of early tricuspid inflow velocity to tricuspid annular early diastolic velocity (TV E/e′), and lower median TV e′ velocity compared to the non-PA dilation group (0.50 vs 0.38 p < 0.01, 4.2 vs 3.6 p < 0.05, and 13.5 vs 15.2 cm/s p < 0.01, respectively). Almost all subjects with PA dilation had improved PA Z-score, RV MPI, and TV E/e′ in the subacute phase (p < 0.01). There were no significant differences in indices of left ventricle function between PA dilation group and non-PA dilation group. In summary, PA dilation was documented in 16 % of acute KD subjects. These subjects were more likely to have echocardiographic indices consistent with isolated RV dysfunction that improved in the subacute phase. The long-term consequence of these findings will require longitudinal studies of this patient population.     

Coronary risk factors in acute Kawasaki disease: Correlation of serum immunoglobulin levels with coronary complications

Abstract Background To determine the usefulness of the IgG z-score (age and sex-standardized serum IgG level) before intravenous gamma globulin therapy (1VGG) in predicting the occurrence or severity of coronary complications in Kawasaki disease (KD).
Methods A case-control study of clinical and laboratory findings with 88 children in the early stage of acute KD who received IVGG (100 or 200 mg/kg for2–5 days) therapy. Of these, 20 cases had persistent coronary arterial lesions (small aneurysm, moderate aneurysm or large aneurysm persisting more than 1 month). The controls comprised 68 children with no coronary aneurysms or transient small aneurysm only observed within 1 month after the onset of KD. The association between serum levels of immunoglobulin G (IgG), IgM, IgA as well as other coronary risk factors previously reported and the occurrence of the coronary arterial lesions was evaluated using logistic regression analysis.
Results: After adjustment for age, gender, total IVGG dose before the 9th illness day and other traditional coronary risk factors, the odds ratio for the persistent coronary aneurysm associated with lower serum IgG r-score (<-0.7485 v.v & -0.7485). was 30.3 (95% confidence interval, 3.8–243.2). Furthermore, the serum IgG z-score was inversely correlated with the severity of the coronary arterial lesion.
Conclusions: The IgG z-score before IVGG therapy in the early stage of KD provides useful information on the risk factors for persistent coronary aneurysm and is a novel, additional indicator for therapy to prevent the coronary complications in acute KD.     

Left Ventricular Diastolic Filling Patterns Associated with Progressive Anthracycline-Induced Myocardial Damage: A Prospective Study

The objective of this study was to examine changes in diastolic function associated with progressive myocardial damage and their implications. We used prospective sequential Doppler echocardiographic studies of left ventricular (LV) function. The study included 125 consecutive children (median age 6.3 years) receiving anthracyclines to cumulative doses between 45 and 1150 mg/m² (median 270 mg/m²). We measured peak early (E) and atrial (A) phase filling velocities, EA ratio, deceleration and isovolumic relaxation times (EDecT and IVRT), heart rate, and fractional shortening (SF). Results were compared serially and with individually paired control data matched for body surface area. Progressive myocardial damage was evidenced by a mean SF decrease of 1 absolute %/100 mg/m² of anthracycline. Six patients developed cardiac failure. After 1–100 mg/m² of anthracyclines, the EA ratio decreased (mean 1.54–1.40, p= 0.02) and IVRT became prolonged (54 vs 52 msec in controls, p= 0.03). EA ratio increased again with the next dose, usually normalizing thereafter. Twelve patients ended treatment with an EA ratio <1 (1 cardiac death) and 17 with EA ratio >2 (2 cardiac deaths). Diastolic abnormalities were not strongly predictive of reduced SF. Modest changes in left ventricular diastolic filling patterns occur during anthracycline treatment of childhood malignancies. Although 20% of patients have significant abnormalities of diastolic filling by the end of treatment, considerable individual variability renders the pathophysiological and clinical implications of the early changes uncertain.