Jun Furui

Quantitation of the Global Right Ventricular Function in Children with Normal Heart and Congenital Heart Disease: A Right Ventricular Myocardial Performance Index

Abstract. Although the assessment of right ventricular (RV) function is important in the clinical management of children with congenital heart disease, available imaging techniques have been limited because of the complex geometry of the right ventricle. A new Doppler index combining systolic and diastolic time intervals (the Tei index) has been reported to be useful for the assessment of global RV function in adults. However, normal values in children, age-related changes, and the clinical utility of the Tei index with regard to congenital heart disease have not been demonstrated. The purpose of this study was to prospectively assess RV function in children with normal heart and congenital heart disease using the Tei index. The subjects included 150 healthy children and 43 patients with congenital heart disease (35 patients with atrial septal defects and 8 patients who had had a Senning operation). The index was defined as the sum of isovolumetric contraction time and isovolumetric relaxation time divided by ejection time and was measured from conventional RV outflow and inflow Doppler velocity profiles. The Tei index was not affected by age in healthy children (0.24 ± 0.04). There was a significant difference in index rating between patients who had had a Senning operation (0.58 ± 0.09) and healthy children (p < 0.01), but there was no significant difference between children with atrial septal defect (0.25 ± 0.13) and healthy children. The Tei index is a feasible approach to use when assessing global RV function in children with congential heart disease.

Sequential Follow-Up Results of Catheter Intervention for Coronary Artery Lesions After Kawasaki Disease Quantitative Coronary Artery Angiography and Intravascular Ultrasound Imaging Study

Background—The purpose of this study was to assess the sequential follow-up results of catheter intervention in Kawasaki disease by use of quantitative coronary angiography (QCA) and intravascular ultrasound imaging. Methods and Results—Catheter intervention was performed on 23 stenotic lesions in 22 patients (aged 2 to 24 years). Percutaneous balloon angioplasty (PBA) was performed in 4 patients, stent implantation in 7, percutaneous transluminal coronary rotational ablation (PTCRA) in 10, and a combination of PTCRA with stent implantation in 2. A total of 21 lesions (91%) were successfully dilated by catheter intervention without major or minor complications. One patient immediately underwent coronary artery bypass grafting (CABG) surgery because stent implantation failed to resolve his lesion. At 4 to 6 months after catheter intervention, 2 restenotic lesions (9%) were detected by QCA in 2 patients who had undergone PBA, and these patients subsequently underwent CABG surgery. In 6 months to 3 years after catheter intervention, no patients showed evidence of ischemic findings. At 3 to 4 years after catheter intervention, QCA and intravascular ultrasound studies were performed on 15 lesions in 14 patients. Two restenotic lesions (13%) were detected by QCA in 2 patients. One of the 2 had stent implantation and underwent CABG surgery, and the other had undergone PTCRA and underwent re-PTCRA. Thirteen patients demonstrated no ischemic findings at 3 to 8 years after catheter intervention. Conclusion—Catheter intervention for Kawasaki disease can be accomplished and can be effective in the short term, but the long-term efficacy should be verified by further study.

Sequential Evaluation of Left Ventricular Myocardial Performance in Children After Anthracycline Therapy

This study prospectively assessed subclinical cardiotoxicity in patients undergoing chemotherapy by using the Tei index combining systolic and diastolic time intervals. A significant difference in the Tei index was observed between patients who received a low dose and those who received a moderate to high dose of anthracycline antibiotic drugs. The Tei index is a sensitive, accurate, and easy approach for detecting subclinical anthracycline cardiotoxicity.

Older Age Is a Risk Factor for the Development of Cardiovascular Sequelae in Kawasaki Disease

Objectives. To clarify the characteristics of Kawasaki disease (KD) in children 6 years and older and to determine whether age is a risk factor for cardiovascular abnormalities. Methods. Patients who had KD and were reported between 1999 and 2000 in the 16th nationwide survey of KD in Japan (n = 15 314) were analyzed. Patients who were aged 6 years or older (older group) were matched with patients who were aged 6 months to 3 years and were treated at the same hospital (younger groups). The total number of analyzed patients was 1498 (749 matched pairs). Results. The proportion of complete KD in the older group was similar to that in the younger group. Recurrent cases in the older group were significantly more common than those in the younger group (9% vs 2%). The proportion of patients who were treated with intravenous γ-globulin in the older group was significantly lower than that in the younger group (82% vs 87%). The proportion of older group patients who were treated with intravenous γ-globulin at or after 7 days of illness was significantly higher than that in the younger group (35% vs 14%). There was a higher prevalence of cardiovascular abnormalities in the older group than in the younger group (20% vs 15%). Multivariate logistic regression analysis showed that older age was an independent risk factor for cardiovascular sequelae (odds ratio: 1.58; 95% confidence interval: 1.01–2.46). Conclusions. In children older than 6 years, age is an independent risk factor for cardiovascular sequelae in KD.

Increased angiogenic growth factor in cyanotic congenital heart disease.

To examine the relationship between the plasma levels of angiogenic growth factors and the severity of cyanosis, 80 patients with cyanotic heart disease (CHD) and 81 healthy controls were studied. Median age and mean arterial blood oxygen saturation respectively were 4.2 years and 81% in CHD subjects and 4.8 years and 98% in controls. Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were measured in plasma using enzyme-linked immunoassay. Plasma VEGF levels in controls depended negatively on age (p < 0.0001) until 3 months, when VEGF was no longer elevated. No such age dependence was found for HGF. Although VEGF levels did not differ between CHD and control subjects up to the age of 3 months, VEGF was significantly elevated in CHD patients older than 3 months compared to controls of similar age (149 ± 106 vs 65 ± 23 pg/ml, p < 0.0001). Moreover, the VEGF levels were negatively correlated with oxygen saturation (p = 0.03) and positively correlated with hemoglobin (p = 0.004) in CHD patients aged between 3 months and 10 years. Although the physiologic elevation of VEGF in the neonatal period decreases rapidly if oxygen saturation is normal, VEGF elevations persist if systemic hypoxia is present.

Quantitative Assessment of Severity of Ventricular Septal Defect by Three-Dimensional Reconstruction of Color Doppler–Imaged Vena Contracta and Flow Convergence Region

Background —The aim of the present study was to investigate the feasibility and potential value of the computer-controlled, 3D, echocardiographic reconstruction of the color Doppler–imaged vena contracta (CDVC) and the flow convergence (FC) region as a means of accurately and quantitatively estimating the severity of a ventricular septal defect (VSD). Methods and Results —We performed a 3D reconstruction of the CDVC and the FC region in 19 patients with an isolated VSD using an ultrasound system interfaced with a Tomtec computer. The variable asymmetric geometry of the CDVC and the FC region could be 3D-visualized in all patients. The 3D-measured areas of CDVC correlated well with volumetric measurements of the severity of VSD (r =0.97, P <0.001). Regression analysis between the shunt flow rate (calculated from the product of the area of CDVC and the continuous Doppler–derived velocity time integral) and the corresponding reference results (calculated by cardiac catheterization) demonstrated a close correlation (r =0.95, P <0.001). There was also a good correlation between shunt flow rates calculated using the conventional 2D, 1-axis measurement of the FC isovelocity surface area with the hemispheric assumption (r =0.95, P <0.001); shunt flow rates calculated using 3D, 3-axis measurements of the FC region (r =0.97, P <0.01); and reference results by cardiac catheterization. However, the 2D method substantially underestimated the actual shunt flow rate. Conclusions —The 3D reconstruction of the CDVC and the FC region may aid in quantifying the severity of VSD.

Soluble forms of the selectin family in children with Kawasaki disease: prediction for coronary artery lesions

Aim: To investigate the relationship between the plasma levels of soluble forms of the selectin family and the incidence of coronary artery lesions (CALs) in patients with Kawasaki disease (KD). Methods: Thirty‐three patients with KD, including group A patients (n= 22) who had no CALs and group B patients (n= 11) who had CALs, as well as age‐matched febrile (n= 10) and afebrile controls (n= 11), were studied. Results: Peak plasma E‐selectin levels (172.0 ± 58.6 ng ml‐1) occurred during the acute phase of KD, while peak plasma P‐selectin levels (260.3 ± 43.2 ng ml‐1) occurred during the subacute phase of the illness (p± 0.05). Plasma L‐selectin levels (1757.3 ± 244.3 ng ml‐1) during the convalescent phase tended to be higher than in either the acute or the subacute phase (not significant). Before intravenous immunoglobulin treatment, the plasma levels of E‐ (225.1 ± 46.8 ng ml‐1) and P‐selectin (259.4 ± 76.2 ng ml‐1) of patients with CALs (n= 11) were significantly higher than those of patients (n= 22) with no CALs (E‐selectin, 131.6 ± 36.9 ng ml‐1; P‐selectin, 184.9 ± 84.6 ng ml‐1; p± 0.05). When a plasma E‐selectin value before immunoglobulin treatment of ± 184.7 ng ml‐1 was used as the cut‐off point, the sensitivity and specificity for the incidence of CALs were 81.8% and 90.9%, respectively. These findings demonstrate the relationship between plasma levels of selectins and disease severity of Kawasaki vasculitis.

Assessment of the Ability of Myocardial Contrast Echocardiography with Harmonic Power Doppler Imaging to Identify Perfusion Abnormalities in Patients with Kawasaki Disease at Rest and During Dipyridamole Stress

The aim of our study was to assess the ability of myocardial contrast echocardiography (MCE) with harmonic power Doppler imaging (HPDI) to identify perfusion abnormalities in patients with Kawasaki disease at rest and during pharmacological stress imaging with dipyridamole. Results were compared with those of 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) imaging as the clinical reference standard. MCE with HPDI was performed on 20 patients with a history of Kawasaki disease. Images were obtained at baseline and during dipyridamole infusion (0.56 mg kg?1) in the apical two- and four-chamber views. Myocardial opacification suitable for the analysis was obtained in all patients. Nine patients with stenotic lesions had a reversible defect after dipyridamole infusion detected by both MCE with HPDI and SPECT, and 3 patients with a history of myocardial infarction had a partially or completely irreversible defect detected by both methods. Three patients with coronary aneurysm without stenotic lesion, 4 patients with regressed coronary aneurysm, and 2 patients with normal coronary artery in acute phase also had normal perfusion at rest and after pharmacological stress by both methods. A 96% concordance (? = 0.87) was obtained when comparing the respective segmental perfusion scores using the two methods at baseline, and an 86% concordance (? = 0.81) was obtained at postdipyridamole infusion. After combining baseline and postdipyridamole images, each segment was labeled as having normal perfusion, irreversible defects, or reversible defects. Using these classifications, concordance for the two methods was 92% (? = 0.87). MCE with HPDI is a safe and feasible method by which to detect asymptomatic ischemia due to severe stenotic lesion, and it may be an important addition to the modalities used to identify patients at risk for myocardial infarction as a complication of Kawasaki disease.

Risk factors associated with the need for additional intravenous gamma-globulin therapy for Kawasaki disease: Factors for IVGG re-treatment in Kawasaki disease

Aim: To investigate the characteristics of patients with Kawasaki disease who needed intravenous gamma‐globulin (IVGG) re‐treatment. Methods: Using the database of the 17th nationwide survey in Japan, a total 11 366 patients were identified and analysed (1855 re‐treatment patients and 9511 responders). Results: Multivariate logistic regression analysis showed that male sex (odds ratio (OR) 1.26; 95% CI 1.14–1.40), complete cases (OR 1.39; 95% CI 1.07–1.80), recurrence (OR 1.47; 95% CI 1.15–1.88), IVGG treatment within 4 d of illness (OR 2.05; 95% CI 1.84–2.27), daily dose of initial IVGG less than 1000 mg/Kg (OR 0.54; 95% CI 0.48–0.61), exanthema (OR 2.03; 95% CI 1.62–2.56), lips and oral lesions (OR 1.57; 95% CI 1.24–1.98), peripheral extremities changes (OR 1.85; 95% CI 1.54–2.22), and cervical lymphadenopathy (OR 1.89; 95% CI 1.66–2.16) were independent risk factors associated with the need for IVGG re‐treatment.

Vascular Wall Morphology and Vascular Elasticity of Coronary Aneurysms in Long-term after Kawasaki Disease: Intravascular Ultrasound Study

The coronary artery (CA) lesion in Kawasaki disease (KD) may be a long term coronary risk factor. We examined the CA wall morphology and elasticity of CA itself using intravascular ultrasound (IVUS) imaging in 70 KD patients (pts) and 10 controls. Consecutive KD pts were followed over more than 10 years from KD onset. The 70 pts comprised 4 groups: Group 1:18 pts with persistent aneurysms. Group 2: 18 pts with CA stenosis. Group 3: 28 KD pts with regressed CA aneurysms, Group 4: 6 pts with normal CA angiography findings at the acute stage of KD. We carefully examined the CA wall morphology on IVUS imagings. The % area change (%AC) of CA lumen in one cardiac cycle was calculated using IVUS imaging to examine the elasticity of the CA wall. The IVUS imaging in Groups 1 and 2 showed intima hyperplasia and various degree of calcification at sites of both persistent coronary aneurysms (intima-media complex (IMC):0.71± 0.22mm, % calcification area (%CA):55.4± 21%) and stenosis (IMC:0.88± 0.44mm, %CA:81.4± 20%,). However, IVUS imaging in Group 3 showed various degrees of the intimal thickening without calcification (IMC:0.48± 0.12mm, %CA:0 %). All IVUS findings in the Group 4, the CA wall echo had a single layered appearance, were similar to that in the control pts. In Group 1 and 2, the CA demonstrated poor elasticity, almost no change in the lumen area (%AC, Group 1:2.4± 1.9%, Croup 2:0.8± 1.5%). In Group 3, A significant poorer elasticity was fond compare to the control pts (Group 3:8.1± 3.7% vs. control 22.0± 13.2%, p<0.05). Group 4 showed no significant difference of elasticity of CA from control (Group 4:21.2± 11.3%). We conclude that long-term persistent coronary aneurysm and regressed coronary aneurysms after KD have abnormal vascular wall morphology and poor vascular elasticity.