Chu-Chuan Lin

Treatment of acute Kawasaki disease: aspirin's role in the febrile stage revisited.

Objective. To evaluate the effect of treatment without aspirin in the acute phase of Kawasaki disease (KD) and to determine whether it is necessary to expose children to high- or medium-dose aspirin. Methods. A total of 162 patients who fulfilled the established criteria of acute KD between 1993 and 2003 were included in this retrospective study. All patients were treated with high-dose intravenous immunoglobulin (IVIG; 2 g/kg) as a single infusion without concomitant aspirin treatment. Low-dose aspirin (3–5 mg/kg per day) was subsequently prescribed when fever subsided. Patients who had defervescence within 3 days after the completion of IVIG treatment were classified as the IVIG-responsive group, and those whose fever persisted for >3 days were classified as the IVIG-nonresponsive group. The 162 patients were divided further into 2 groups: those who were treated with IVIG before illness day 5, and those who were treated after illness day 5. We compared the response rate of IVIG therapy, duration of fever, and incidence of coronary artery abnormalities (CAAs) between these groups. Results. A total of 153 patients were classified into the IVIG-responsive group, and 128 (83.66%) of them had defervescence within 24 hours after completion of IVIG therapy. Nine (5.56%) patients were classified into the IVIG nonresponsive group, and all received additional IVIG (2 g/kg) without aspirin. Six (66.67%) had defervescence within 3 days after additional therapy. Patients in the IVIG-nonresponsive group had a significantly higher incidence of CAAs than those in the IVIG-responsive group (25% vs 2.92%). In the group that was treated before illness day 5 (n = 16), all patients had defervescence within 3 days after IVIG therapy and 13 (81.25%) had defervescence within 24 hours. In the group that was treated after illness day 5 (n = 146), 137 (93.84%) patients had defervescence within 3 days and 115 (78.77%) had defervescence within 24 hours. One (6.67%) patient in the group that was treated before illness day 5 got a new onset of CAAs, as did 5 (3.85%) in the group that was treated after illness day 5. There was no statistically significant difference in the response rate of IVIG therapy, duration of fever, and incidence of CAAs between these 2 groups. Conclusion. The results of our study indicate that the treatment without aspirin in acute stage of KD had no effect on the response rate of IVIG therapy, duration of fever, or incidence of CAAs when children were treated with high-dose (2 g/kg) IVIG as a single infusion, despite treatment before or after day 5 of illness. We conclude that it seems unnecessary to expose children to high- or medium-dose aspirin therapy in acute KD when the available data show no appreciable benefit in preventing the failure of IVIG therapy, formation of CAAs, or shortening the duration of fever.

Effects of a classroom-based weight-control intervention on cardiovascular disease in elementary-school obese children.

BACKGROUND Childhood obesity has become a growing public health issue in Taiwan. Obese children have risk factors for type 2 diabetes and cardiovascular disease. In this prospective study, we investigated the effect of a twelve-week heart health education and physical activity program on body weight and risk factors for type 2 diabetes and cardiovascular disease. METHODS Subjects were 120 obese fifth graders (65 boys and 55 girls, aged 10-13 years (mean 10.6 yrs), body mass index (BMI) at the 95th percentile or more) and were randomly assigned to an intervention group (n=60) or control group (n=60). The intervention group received a twelve-week heart health education and physical activity program, while the control group did not. In both groups, a series of examinations were done at baseline and post-test, including height, weight, BMI, body fat, blood pressure (BP), physical fitness (800-meter running test), heart health knowledge, and serum biochemistry. Differences for baseline and post-test data were compared between both groups. RESULTS Mean changes in the intervention group versus control group were significant for weight (P = 0.024), BMI (P = 0.047), percentage body fat (P = 0.008), physical fitness (800-meter running test) (P = 0.025), heart health knowledge (P = 0.006), total cholesterol (P = 0.027), triglycerides (P = 0.018), high-density lipoprotein cholesterol (HDL-C) (P = 0.009), low-density lipoprotein cholesterol (LDL-C) (P = 0.041), sugar (P = 0.035), insulin (P = 0.007), and insulin resistance (HOMA-IR) (P = 0.028). At post-test, weight, BMI, body fat, total cholesterol, triglycerides, LDL-C, sugar, insulin and HOMA-IR had decreased, but HDL-C had increased in the intervention group. CONCLUSIONS A classroom-based weight-control intervention provides educational programs to promote cardiovascular health in children. This intervention is simple, practical, and beneficial for elementary school children.

Recent advances in the treatment of Kawasaki disease

Abstract Kawasaki disease (KD) is acute systemic vasculitis that occurs mainly in infants and children under 5 years of age. The etiology of KD remains unknown. KD is liable to be complicated by coronary artery lesions (CALs), which develop in approximately 15–25% of untreated KD children and in approximately 5% of KD children after intravenous immunoglobulin (IVIG) therapy. A single high dose of IVIG (2 g/kg) is the gold standard therapy in the acute stage of KD. However, approximately 8–38% of children are unresponsive to initial IVIG treatment and at increased risk for CAL development. Anti‐inflammatory high doses of aspirin are recommended in conjunction with IVIG, but our study demonstrated that there is no evidence of efficacy in preventing CAL development. The usefulness of steroids in initial therapy for KD or treatment of IVIG‐resistant patients is not well established. Other immunosuppressive therapies, including infliximab, have been used in the treatment of refractory KD, but merit additional investigation. Subclinical atherosclerosis may develop early in KD patients, which makes early initiation of therapy to improve chronic inflammation an important issue. Future multicenter studies may help to define the optimal management of KD patients.

Reappraisal of the Prostaglandin E1 Dose for Early Newborns with Patent Ductus Arteriosus-Dependent Pulmonary Circulation

OBJECTIVES The usual initial dose of prostaglandin E1 (PGE1) for ductal-dependent congenital heart disease (CHD) is 50-100 ng/kg/minute. The aim of this study was to review our experience of a low initial dose of PGE1 treatment in early newborns with congenital heart disease and patent ductus arteriosus (PDA)-dependent pulmonary flow. METHODS We reviewed the clinical data of 33 newborns with CHD and PDA-dependent pulmonary circulation who were admitted from January 2005 to December 2010. Clinical parameters were collected, including, PGE1 dosage, oxygenation condition, vital signs, and other related clinical parameters during admission. Echocardiography was employed to assess the status of the PDA as clinically indicated. RESULTS Thirty-three newborns, including 17 males and 16 females, with CHD and PDA-dependent pulmonary circulation were enrolled in the study. Their mean age was 2.9 ± 5.1 (within the range of 1-26) days with a median of 1.0 day. Among the 33 cases, 25 were diagnosed with pulmonary atresia and eight with critical pulmonary stenosis. Twenty-five of our patients were treated with the initial low-dosage regimen of 20.0 ± 7.4 ng/kg/minute in our neonatal intensive care unit. None of these 25 patients with had significant apnea necessitating intubation and none had hypotension, fever, convulsion or cortical hyperostosis. Three of the eight patients who were treated with high-dose PGE1 (39 ± 13.2 ng/kg/minute) before referral to our unit had apnea and intubation after PGE1 use. All patients had adequate PDA patency with a low maintenance dose of 10.5 ± 5.3 ng/kg/minute before operation under our protocol. CONCLUSION In our experience, adequate PDA flows in early newborns with CHD and PDA-dependent pulmonary circulation could be achieved at a much lower dose than recommended in the literature. The lower dose of PGE1 also causes much fewer complications, such as apnea, fever, and hypotension. For early newborns with CHD and PDA-dependent pulmonary circulation, treatment with a lower initial dose of PGE1 of 20 ng/kg/minute and a maintenance dose of 10 ng/kg/minute is recommended.

Idiopathic Dilated Cardiomyopathy in Children: A Single Medical Center's Experience

Background: The prognosis of patients with idiopathic dilated cardiomyopathy (DCM) is poor. Most patients die while waiting for cardiac transplantation because of the small number of donors in Taiwan. The purpose of this study was to review our experience with pediatric patients diagnosed with idiopathic DCM and attempt to discover prognostic factors. Methods: Eighteen patients with idiopathic DCM presenting between 1990 and 2004 were identified. They were classified into 2 groups according to outcome: group 1 comprised 13 patients who died; group 2 comprised 5 who survived. Clinical findings and laboratory investigations were compared between the 2 groups. Results: The age at initial diagnosis for the 18 patients (11 males, 7 females) ranged from fetus to 13 years (median, 3 months). The follow‐up period ranged from 12 days to 44 months (median, 7 months) in group 1, and from 1 to 48 months (median, 39 months) in group 2. Of the 18 patients, 13 (72%) died: 11 died from severe heart failure while waiting for cardiac transplantation. The cumulative survival rate was 50% at 1 year and 28% at 4 years. The presence of arrhythmia and low left ventricular ejection fraction were predictive of a poor outcome. Conclusion: The diagnosis of idiopathic DCM in children is associated with a generally poor prognosis. The lack of available donors results in significant mortality for pediatric patients awaiting transplantation. Advocating organ donation to increase the size of the organ donor pool is needed to significantly reduce the mortality rate in such patients.

Interleukin-18 and coronary artery lesions in patients with Kawasaki disease

Background: Interleukin‐18 (IL‐18) plays an important role in mediating cytokine cascade leading to coronary artery lesions (CALs) in Kawasaki disease (KD). However, our research suggested that the literature regarding IL‐18 and KD is limited. Consequently, this study aimed to evaluate the correlation between IL‐18 and CALs in patients with KD. Methods: In this prospective study of 14 children with KD (seven without and seven with CALs in the acute phase), we obtained patient measurements of a series of serum IL‐18 levels in the acute, subacute, and convalescent phases. Serum IL‐18 levels were measured with a Bio‐Plex cytokine assay. Control samples were obtained from 18 febrile children with viral infection. Results: Compared with febrile controls, patients with acute‐stage CALs [postintravenous immunoglobulin (post‐IVIG) period] had a significantly higher IL‐18 level (88.4 ± 20.7 vs 56.0 ± 35.0 pg/mL, p = 0.006). However, those without acute‐stage CALs (post‐IVIG period) lacked similarly elevated IL‐18 level readings (62.0 ± 40.6 vs 56.0 ± 35.0 pg/mL, p = 0.762). The IL‐18 level of patients with acute‐stage CALs did not decrease significantly until the convalescent phase (97.4 ± 55.8 vs 38.7 ± 22.6 pg/mL, p = 0.018), but for those without CALs, it decreased significantly in the subacute phase (60.2 ± 37.4 vs 23.6 ± 13.8 pg/mL, p = 0.018). In the subacute stage, there was a significant difference of IL‐18 level between patients with and without acute‐stage CALs (p = 0.048). Conclusion: Our data show that IL‐18 levels were elevated in the acute phase of KD and might be related to the formation of CALs.

A noninvasive sizing method to choose fitted Amplatzer septal occluder by transthoracic echocardiography in patients with secundum atrial septal defects

To simplify the conventional procedure, we developed a technique for transcatheter closure of atrial septal defects (ASDs) under transthoracic echocardiographic (TTE) sizing without balloon sizing. At present, device closure of interatrial communication has become a well-established technique to adequately treat severe left-to-right shunt associated with ASDs. During the traditional procedure, fluoroscopy with the waist of a compliant balloon is used to determine the appropriate size of the closure device and defect sizing. Choice of adequate closure device using transthoracic echocardiography (TTE) has been hitherto unreported. Between December 2002 and August 2004, 40 patients (15 males, 25 females, mean age 11.7 ± 7.8 years) with secundum ASDs underwent transcatheter closure at our institution. In group 1, 30 patients had the procedure by balloon sizing and TTE sizing. In 10 patients (group 2), TTE sizing was used as the sole tool for selecting device size and the device size was chosen to be based on the Amplatzer septal occluder (ASO) size and TTE size ratio in group 1. The procedure was performed under continuous transesophageal echocardiographic monitoring with general anesthesia. A correlation was found between TTE and stretched balloon sizing diameter SBD (y = 1.2645x − 1.4465; R2 = 0.9861), and between TTE size and ASO size (y = 1.3412x − 1.2864; R2 = 0.9929) in group 1. In group 2, a statistical correlation between TTE and ASO (y = 1.3419x − 0.1172; R2 = 0.9934) was also found. Good linear regression between TTE size and ASO chosen size was noted in group 1 and group 2 (R2 = 0.99). In group 2, successful device implantation was accomplished in all patients whose device size was chosen to be based on the ASO and TTE ratio in group 1. Transthoracic echocardiographic sizing is a safe and ideal method to measure interatrial defect and choose the occluding device, respectively. With our experience, the sizing based on TTE is generally easier than measurement from the balloon sizing.

Oscillometric Ambulatory Blood Pressure Values in Healthy Children

To assess the feasibility of ambulatory blood pressure monitoring (ABPM) and establish reference values for ABPM in normal children and adolescents, 24-hour ABPM was performed in 120 normotensive, nonobese subjects, aged from 6 to 14 years (58 males, age 10.1 +/- 2.8 years; 62 females, age 9.7 +/- 3.1 years; mean +/- SD). The subjects were classified into three age groups: group A (6-8 years, n=40, 23 males, 17 females), group B (9-11 years, n=40, 21 males, 19 females), and group C (11-14 years, n=40, 18 males, 22 females). ABPM was carried out using an oscillometric device with appropriate cuff size. The monitor was programmed to measure BP every 15 min during the day (6 a.m. to 10 p.m.) and every 30 min during the night (10 p.m. to 6 a.m.). Successful rates (recording time=24 hours and > 40 recordings) were 83%, 88%, and 93% in groups A, B, and C, respectively. The recordings of 15 subjects (7 in group A, 5 in group B, 3 in group C) were not analyzed because of incomplete readings. The 24-hour mean systolic/diastolic blood pressure (SBP/DBP) for males and females were 106 +/- 7/65 +/- 5 and 105 +/- 6/64 +/- 5, 110 +/- 6/66 +/- 5 and 109 +/- 5/65 +/- 4, and 115 +/- 7/67 +/- 6 and 113 +/- 6/66 +/- 4 mmHg in groups A, B, and C, respectively. The daytime mean SBP/DBPfor males and females were 110 +/- 7/73 +/- 4 and 109 +/- 8/72 +/- 5, 117 +/- 5/75 +/- 4 and 115 +/- 8/74 +/- 6, and 122 +/- 6/76 +/- 4 and 120 +/- 7/75 +/- 6 mmHg in groups A, B, and C, respectively. The nighttime mean SBP/DBP for the corresponding sex and age groups were 97 +/- 8/58 +/- 5 and 95 +/- 7/57 +/- 6, 101 +/- 8/59 +/- 6 and 99 +/- 7/57 +/- 5, and 105 +/- 7/58 +/- 5 and 103 +/- 6/56 +/- 4 mmHg, respectively. The first fall in BP appeared after lunch (approximately 1:00 pm) and the second fall appeared during the night hours (11:00 pm to 6:00 am). There was a significant correlation between 24-hour mean ambulatory SBP and age (r=0.48, P < 0.001). In contrast, ambulatory DBP and age were not significantly correlated. A nocturnal fall of SBP/DBP was observed in all age- and sex-subgroups. This study showed that ABPM was reproducible and accurate. The normal ambulatory blood pressure (ABP) values in the pediatric age group have not been reported in Taiwan. The distribution of ABP observed in this study could serve as a preliminary reference. A multicenter study may be done to provide normal ranges of ABP in Taiwan for clinical purposes. Further studies are necessary to elucidate the role of ABPM in children.

Serum HDL Level at Acute Stage of Kawasaki Disease

Kawasaki disease is a disease of acute vascular inflammation of unknown etiology and HDL is a known risk factor of vascular damage. So far, there is no specific serum marker for KD. The previous study has shown a remarkable change of serum HDL in the patients with KD. To find whether changes in serum HDL level is a specific serum marker for early diagnosis of KD, we measured the concentration of HDL, LDL, TC, TG and CRP immediately after admission and one week later in three groups of patients (56 patients with KD, 38 patients with clinical viral infection, and 42 patients with bacterial infection). There was a significant decrease of HDL and increase of TG immediately after admission in three groups of patients. HDL and TG did not return to normal one week later. HDL level is more adversely affected in severe diseases than in mild diseases. Our results indicated that low HDL level is noted in various acute infection and is not a specific serum marker in the early stage of Kawasaki disease. It is interesting that low HDL is a universal phenomenon in this series. Further research is needed to explain the mechanism of lipid alterations and its consequences.

The Long-term Outcome of Children with Isolated Congenital Complete Atrioventricular Block

Patients with isolated congenital complete atrioventricular block (CCAVB) may revert to a lower degree of atrioventricular block and do not require pacemaker treatment. The change of rhythm is less well studied in pediatric patients. The aim of this study was to report the long-term outcome of pediatric patients with isolated CCAVB at our institution, with emphasis on restoration of sinus rhythm. We reviewed the medical records of 16 consecutive children with isolated CCAVB at our institution. They were divided into a prenatal group (n=9) and a postnatal group (n=7). In the prenatal group, with follow-up of 28 months (median, range 1-154 months), one patient without symptoms had transient restoration of sinus rhythm and did not require pacemaker therapy, five patients required pacemaker therapy and three of them died, and the remaining three patients without symptoms did not require pacemaker therapy. In the postnatal group, with follow-up of 84 months (median, range 14-133 months), one patient without symptoms had restoration of sinus rhythm and did not require pacemaker therapy, three patients required pacemaker therapy and survived, and the remaining three patients without symptoms did not require pacemaker therapy. Compared to the postnatal group, the prenatal group needed earlier pacing and had higher rate of maternal autoantibodies. There were no significant differences in sex, pacemaker implantation rate, dilated cardiomyopathy, and mortality rate between the two groups. Pacemaker implantation is indicated in most patients with isolated CCAVB, but a change to a lower degree of block can occur in some pediatric patients who may not require pacemaker implantation.