Satoru Iwashima

Ultrasound-guided versus landmark-guided femoral vein access in pediatric cardiac catheterization.

BackgroundThis study aimed to evaluate whether an ultrasound-guided technique can improve upon a landmark-guided technique in achieving femoral vein access in pediatric cardiac catheterization.MethodsThis study examined 87 consecutive subjects with a median age of 2 years (range, 1 month to 19 years) who had congenital or other heart disease. Femoral vein puncture was attempted using either an ultrasound-guided technique (US group, n = 43) or a landmark-guided technique (LM group, n = 44). The patients were assigned alternately to either an ultrasound- or landmark-guided group. Overall success and traumatic complication rates were compared between the two groups, as well as the influence of patient size and age.ResultsThe overall rate of success in achieving femoral vein access did not differ between the two groups. Among the successful cases in the two groups, there were no significant differences in patient size or age. Inadvertent femoral artery puncture occurred with 3 (7%) of 43 patients in the US group and with 14 (31.8%) of 44 patients in the LM group, for a significantly higher complication rate in the LM group (p < 0.01).ConclusionsUltrasound-guided access to the femoral vein minimizes the complication of inadvertent arterial puncture as compared with the landmark-guided approach.

Endothelial Dysfunction in Children within 5 Years after Onset of Kawasaki Disease

OBJECTIVE To evaluate endothelial function in children within 5 years after the onset of Kawasaki disease (KD). STUDY DESIGN A total of 46 children were enrolled prospectively as follows: 9 patients with KD and coronary artery lesions composed group 1, 15 patients with KD but without coronary artery lesions composed group 2, and 22 healthy age- and sex-matched children composed group 3. Flow-mediated dilatation (FMD) of the brachial artery, intima-media thickness of the common carotid artery, and biologic characteristics were compared among the 3 groups. Differences in the factors associated with endothelial function after KD were examined as well. RESULTS The mean age of the study group was 6.5 ± 1.7 years. The patients with KD were studied at a median interval of 3.3 years (IQR, 2.0-4.4 years) from the onset of disease. The percent FMD (%FMD) was significantly lower in group 1 patients (median, 4.4%; IQR, 2.6%-5.7%) compared with both group 2 (median, 9.1%; IQR 6.6%-10.7%; P < .01) and group 3 (median, 11.1%; IQR, 10.1%-13.9%, P < .01). The %FMD was statistically significantly lower in group 2 compared with group 3 (P < .05). There were no significant differences in the intima-media thickness among the 3 groups. There was a significant negative correlation between %FMD and the total duration of fever (r = -0.50; P = .013). CONCLUSION The children with KD already had arterial endothelial dysfunction within 5 years after the onset of illness. The longer the duration of fever, the greater the risk of inflammation-induced endothelial dysfunction.

Ulinastatin Therapy in Kawasaki Disease

Background and objective:Ulinastatin therapy may be an additional therapeutic approach to Kawasaki disease (KD). This study set out to determine whether primary intravenous ulinastatin therapy has more beneficial effects than intravenous immunoglobulin (IVIG) therapy in the acute phase of KD, and whether addition of ulinastatin to IVIG might improve outcomes in KD.Methods:Patients were included in the study if they had a diagnosis of KD with a Harada’s score that predicted coronary artery lesions. Subjects were selected to receive either primary ulinastatin therapy (30 000 U/kg/day for 3 days) or IVIG therapy (1 g/kg/dose) using sealed envelopes. Of the 27 study subjects, 18 were assigned to the ulinastatin group, and nine to the IVIG group. IVIG therapy could be added to ulinastatin therapy if patients experienced adverse effects of ulinastatin, were found to have complicated coronary artery lesions, or developed prolonged fever or elevated white blood cell counts or C-reactive protein levels.Results:More patients receiving IVIG as primary therapy had reduced fever and C-reactive protein levels than patients receiving ulinastatin as primary therapy. Five patients in the ulinastatin group (28%) improved without additional IVIG therapy. These patients had lower white blood cell counts and C-reactive protein levels on admission.Conclusions:Primary ulinastatin therapy prevented coronary artery lesions in only 28% of cases of KD with a Harada’s score predictive of such lesions. Primary ulinastatin therapy may not be the treatment of first choice for preventing coronary artery lesions in patients with KD.

Prevalence of congenital heart disease assessed by echocardiography in 2067 consecutive newborns

Aim:  There are discrepancies in the reported prevalence of congenital heart disease (CHD). This study prospectively evaluated the prevalence of CHD in consecutive newborns using echocardiographic screening.

Abdominal obesity is associated with cardiovascular risk in Japanese children and adolescents

Abstract Background: Metabolic syndrome is listed as a risk for atherosclerosis. However, changes in that risk during childhood and adolescence have not been well-documented. It is also unclear whether individuals with abdominal obesity, but with as yet undiagnosed metabolic syndrome, have cardiovascular risks. Methods and results: Ninety-two patients were studied at the Hamamatsu University School of Medicine Department of Pediatrics. Physical measurements including abdominal circumference (AC), body mass index (BMI), body fat (BF), intima media thickness (IMT), arterial elasticity: beta index (Beta), carotid artery compliance (CAC), and Young’s elastic modulus (YEM) using ultrasonography were taken. A positive correlation between systolic blood pressure, AC, BMI, and BF was observed (AC, r=0.717, p<0.001; BMI, r=0.672, p<0.001; BF, r=0.518, p<0.001). IMT showed a weak positive correlation with AC, BMI and BF (AC, r=0.211, p=0.044; BMI, r=0.233, p=0.025; BF, r=0.232, p=0.026). The relationship between AC, BMI, BF and arterial elasticity, especially in AC, positively correlated with beta index and YEM but negatively correlated with CAC. Conclusion: We suggest that AC is the most sensitive marker in the detection of arterial elasticity, even in school age children. Earlier pre-diagnostic intervention, especially in the prevention of abdominal obesity, may reduce the incidence of metabolic syndrome in children and adolescents.

B-type natriuretic peptide and N-terminal pro-BNP in the acute phase of Kawasaki disease

BackgroundThis study was undertaken to identify factors correlating with plasma levels of B-type natriuretic peptide (BNP) and its N-terminal portion (NTpro BNP) in the acute phase of Kawasaki disease (KD).MethodsThis study included 91 patients with KD treated at a hospital affiliated to Hamamatsu University School of Medicine between October 2003 and June 2011. We quantified BNP and NT-pro BNP in the acute phase. The BNP level was expressed as the NT-pro BNP level using the formula NT-pro BNP=9.080×BNP0.923. We sought relationships between NT-pro BNP values and different clinical and laboratory data in the acute phase of KD.ResultsOf the 91 patients, 14 failed to respond to the initial intravenous immunoglobulins therapy. NTpro BNP levels were significantly higher in these nonresponders than in the responders (1689.3±1168.8 pg/ dL vs. 844.4±1276.3 pg/dL, P<0.001). Seventeen patients developed coronary artery lesions, but this was not associated with NT-proBNP levels. NT-pro BNP was positively correlated with CRP (r=0.421, P<0.001) and negatively correlated with the hematocrit (r=−0.206, P=0.050), Na value (r=−0.214, P=0.041) and albumin level (r=−0.345, P<0.001). Stepwise multiple linear regression analysis with NT-pro BNP as a dependent variable revealed significant correlations with CRP and albumin (beta=0.345, P=0.001; beta=−0.225, P=0.027).ConclusionsA high level of NT-pro BNP in acute phase KD is associated with systemic inflammatory responses and increased vascular permeability. The NT-pro BNP level is a useful marker to identify potential non-responders to IVIG among KD patients.

Importance of C-Reactive Protein Level in Predicting Non-Response to Additional Intravenous Immunoglobulin Treatment in Children with Kawasaki Disease

AbstractBackground: Intravenous immunoglobulin (IVIG) therapy in the acute stage of Kawasaki disease (KD; mucocutaneous lymph node syndrome) is the treatment of first choice for preventing the development of coronary artery lesions (CALs). Failure of initial treatment with IVIG remains the most consistent risk factor for CALs. However, there are few reports on non-responders to additional IVIG therapy in KD. Objective: The goal of the present study was to predict non-responders to additional IVIG therapy in children with KD. Methods: This was a retrospective study aimed at predicting non-responders to additional IVIG therapy for KD in a cohort of 446 patients. The IVIG response group (‘responders’) was defined as those patients who were afebrile 48 hours after administration of initial IVIG. The IVIG non-response group (‘non-responders’) was defined as those patients who remained febrile 48 hours after administration of initial IVIG and was divided into two subgroups: (i) those patients who remained febrile 48 hours after administration of additional IVIG (non-responders 1), and (ii) those patients who were afebrile 48 hours after additional IVIG (non-responders 2). Results: Ninety-one patients received additional IVIG; of these, 25 patients (non-responders 1) received additional rescue therapy because no improvement was observed and 66 patients (non-responders 2) were afebrile. Mean ± SD C-reactive protein (CRP) levels were higher in non-responders 1 than in non-responders 2 (12.05 ± 5.14 vs 7.67 ± 4.99 mg/dL; p = 0.002). The optimal cutoff point of sensitivity and specificity for predicted non-responders was ≥8 mg/dL. The sensitivity and specificity for prediction of IVIG response was 76.0% and 63.6%, respectively. Forty-three patients had a CRP level of ≥8 mg/dL after initial IVIG, 18 of whom developed CALs (eight persistent lesions and ten transient lesions). Forty-eight patients had a CRP level of <8mg/dL after initial IVIG, of whom only eight developed CALs (all transient). Conclusion: We have discovered a biomarker able to identify KD patients at high risk of complications who require additional IVIG treatment, thus avoiding overtreatment of low-risk individuals. We suggest that patients who have a CRP level of ≥8 mg/dL after initial IVIG are likely to fail additional IVIG and may require further IVIG plus rescue therapy.

Association of abdominal aortic wall thickness in the newborn with maternal factors.

PURPOSE The goal of the present study is to carry out prospective echocardiographic measurements of intima-media thickness (IMT) in the abdominal artery of newborns. METHODS Study subjects were 96 mothers and their newborns. We measured the adjusted IMT (aIMT, mm/mm) of newborn abdominal arteries by high-resolution ultrasound and evaluated the association of aIMT with various maternal and newborn factors. RESULTS Negative correlations were observed between aIMT and gestational age (r = - 0.678, p < 0.01) and positive correlations between aIMT and placenta-to-fetus weight ratio (r = 0.418, p < 0.01). Comparing the small-for-gestational-age (SGA) versus appropriate-for-gestational-age (AGA) categories, aIMT in the SGA (n = 14) was greater than in the AGA (n = 82), with values of [0.115 (0.117) mm/mm versus 0.084 (0.074) mm/mm, p < 0.01], respectively. A multiple linear regression analysis was performed with aIMT as a dependent variable, and significant correlations were noted with gestational age (R2 = 0.524, β = - 0.515, p < 0.001 for gestational age). CONCLUSION On the basis of these findings, we suggest that aIMT thickness is associated with placenta-to-fetus weight ratio and gestational age, and that increased values of aIMT in SGA may indicate presence of a latent link to cardiovascular disease that might otherwise go undetected in infancy.

Dynamics of endogenous glucocorticoid secretion and its metabolism in Kawasaki disease

OBJECTIVE Kawasaki disease (KD) is a severe inflammatory disease that occurs in childhood. Recently, the initial corticosteroid therapy for KD has been reconsidered because its efficacy is controversial. The aim of this study was to evaluate the dynamic change in endogenous glucocorticoid levels and their relation with 11beta-hydroxysteroid dehydrogenase (11beta-HSD) activity in the acute phase of KD. STUDY DESIGN Sixteen KD patients were investigated. Cortisol and cortisone levels, the cortisol/cortisone ratio and C-reactive protein (CRP) levels were measured on admission, before the first intravenous immunoglobulin (IVIG) therapy and convalescence. RESULTS The 16 patients were divided into two groups. Group A included patients who received the first IVIG on admission and blood samples were collected before the first IVIG and convalescence. Group B included patients whose blood samples were collected at three different time points (on admission, before the first IVIG, and convalescence). CRP and cortisol levels and the cortisol/cortisol ratio were markedly higher before the first IVIG than those of convalescence in all patients except in one patient. In Group B patients, both serum cortisol levels and the cortisol/cortisone ratio on admission were significantly increased compared with those before the first IVIG (cortisol: p<0.005, cortisol/cortisone: p<0.001). CONCLUSIONS Decreases in cortisol levels and the cortisol/cortisone ratio before the first IVIG may be explained by a reduction in adrenal secretion and/or local glucocorticoid action through 11beta-HSD activity. These findings suggest that exogenous glucocorticoid treatment in combination with the first IVIG at the acute stage may play a synergetic role in KD.

Brain natriuretic peptide levels in Kawasaki disease: A case report

In this report, we determined the serial changes in plasma brain natriuretic peptide (BNP) levels in a 4-month-old girl with giant coronary artery aneurysm (CAA) due to Kawasaki disease (KD). The patient was brought to her physician following two days of fever and the development of full body erythema. She was admitted to a local general hospital, at which time her white blood cell count (WBC) was 9200 /ml, C-reactive protein (CRP) was 1.6 mg/dl, and aspirate aminotransferase (AST) was 130 IU/dl. Initially, she was treated for a bacterial infection and urticaria, however this approach failed to reduce her fever after 5 days. In addition, she developed inflamed conjunctivae, a strawberry tongue, edema of the peripheral extremities, and a diffuse rash. She had no redness and crust at the site of a bacillus Calmette– Guérin (BCG) inoculation, although she received a BCG vaccine at 3 months old. After 5 days in the hospital, she was diagnosed with KD. Echocardiography failed to reveal any dilatations of her right or left coronary arteries. She did not respond to an initial infusion of 2 g/kg intravenous immunoglobulin (IVIG) with oral aspirin (30 mg/kg), and received an additional IVIG infusion of 2 g/kg 2 days later. Her fever persisted and she was placed on i.v. prednisolone (2 mg/kg/dose) for 3 days starting at 9 days after fever onset. Again, her fever persisted, and, at 11 days after onset, she was reexamined using echocardiography. No pericardial effusion was observed, but her coronary arteries appeared dilated. Therefore, prednisolone was discontinued. At 12 days after fever onset, the patient was referred to our institution. Upon admission to our institution, physical examination revealed a mild cardiac systolic murmur. The patient’s blood pressure was 82/40 mmHg and her respiratory rate was 41 breaths/min. Echocardiography revealed dilations in the diameter of her right and left coronary arteries of 2.8 mm and 2.9 mm, respectively, and mild mitral regurgitation. Left ventricular cardiac function was within normal range. Systolic left ventricular fractional shortening was 33%, as assessed by M-mode echocardiography, and the E/A ratio was determined using Doppler echocardiography to be 1.28. The liver was not palpable below the right costal margin. Laboratory findings included a WBC count of 30 700 /ml, hemoglobin at 8.8 g/dl, a platelet count of 72.8 ¥ 10 /ml, total protein of 7.8 g/dl, serum immunoglobulin G levels of 3221 mg/dl, a CRP of 3.9 mg/dl, and a plasma BNP of 103 pg/dl. Serum levels of tumor necrosis factor (TNF)-a were less than 5 pg/ml. On day 14 and 15 after fever onset, plasma exchange was undertaken in an attempt to reduce the patient’s fever and coronary artery dilations. Plasma exchange was performed as previously reported. During plasma exchange, blood was drawn and plasma was infused simultaneously using 6 Fr double-lumen catheters (heparin: 100 U/kg per day) in the femoral vein. For plasma replacement, a 5% albumin solution was prepared. Although plasma exchange was scheduled to be performed for 3 consecutive days, she became afebrile and her WBC and CRP decreased after 2 days. On day 22 after onset, in spite of the fact that her plasma BNP levels had diminished, echocardiography revealed a progressive pericardial effusion and a giant CAA (Fig. 1). Therefore, we administered oral loop diuretics and spironolactones. Her pericardial effusion and mild mitral valve regurgitation improved sufficiently from day 39 through day 55 after onset (Fig. 2). At 15 days, 22 days, and 53 days after onset, left ventricular cardiac function was observed to be within normal range with systolic left ventricular fractional shortening between 30% and 38% and the E/A ratio between 1.27 and 1.30. During the patient’s convalescence, her laboratory findings, electrocardiograms, and myocardial scintigraphy all failed to reveal any evidence of myocardial ischemia. On day 57 after onset, coronary angiography revealed the presence of giant CAA in the patient’s right and left coronary arteries (Fig. 3). The left anterior and circumflex coronary aneurysm was approximately 8 mm and the proximal right coronary aneurysm was approximately 12 mm. On day 68 after onset, the patient was discharged, but continued to take oral aspirin, ticlopidine, and warfarin sodium.