Yayoi Nakahata

The strategy of immune globulin resistant Kawasaki disease: A comparative study of additional immune globulin and steroid pulse therapy

BACKGROUND We compared the clinical utility of additional intravenous immune globulin (IVIG) therapy with the clinical utility of steroid pulse therapy in patients with IVIG-resistant Kawasaki disease. METHODS We enrolled 164 patients with Kawasaki disease who were treated with a single dose of IVIG (2 g/kg) and aspirin (30 mg/kg per day). Twenty-seven of these patients (16%) were resistant to the initial IVIG treatment. We compared the effectiveness of treatment strategies for the initial IVIG-resistant 27 patients, 14 of these patients were treated with additional IVIG therapy, and the other 13 patients were treated with steroid pulse therapy (methylprednisolone 30 mg/kg per day for 3 days). RESULTS Three patients in the group receiving additional IVIG treatment had coronary artery aneurysms (21.4%), no patients had coronary artery aneurysm in the steroid pulse therapy group; the difference in the incidence of coronary artery aneurysm was not statistically significant. The duration of high fever after additional treatment in the steroid pulse therapy group (1 ± 1.3 days) was significantly shorter than that in the additional IVIG treatment group (3 ± 2.4 days; P < 0.05). The medical costs were significantly lower in the steroid pulse therapy group than in the additional IVIG treatment group. CONCLUSION Steroid pulse therapy was useful to reduce the fever duration and medical costs for patients with Kawasaki disease. Steroid pulse therapy and additional IVIG treatment were not significantly different in terms of preventing the development of coronary artery aneurysm.

Clinical score and transcript abundance patterns identify Kawasaki disease patients who may benefit from addition of methylprednisolone.

Intravenous immunoglobulin (IVIG) treatment-resistant patients are high risk of developing coronary artery lesions with Kawasaki disease. The IVIG-responsive (Group A; n = 6) and IVIG-resistant patients (Group B) were predicted before starting the initial treatment using the Egami scoring system and randomly allocated as a single-IVIG treatment group (group B1; n = 6) or as a IVIG-plus-methylprednisolone (IVMP) combined therapy group (group B2; n = 5). We investigated the transcript abundance in the leukocytes of those patients using a microarray analysis. Five patients in group A and one patient in group B1 responded to initial IVIG treatment. All group B2 patients responded to IVIG-plus-IVMP combined therapy. Before performing these treatments, those transcripts related to IVIG resistance and to the development of coronary artery lesions, such as IL1R, IL18R, oncostatin M, suppressor of cytokine signaling-3, S100A12 protein, carcinoembryonic antigen-related cell adhesion molecule-1, matrix metallopeptidase-9, and polycythemia rubra vera-1, were more abundant in group B patients in comparison with group A patients. Moreover, those transcripts in group B2 patients were more profoundly and broadly suppressed than group B1 patients after treatment. This study elucidated the molecular mechanism of the effectiveness of IVIG-plus-IVMP combined therapy.

Transthoracic Doppler assessment of coronary flow velocity reserve in children with Kawasaki disease: Comparison with coronary angiography and thallium-201 imaging

OBJECTIVES The purpose of this study was to determine the feasibility of coronary flow velocity reserve (CFVR) measurement by transthoracic Doppler echocardiography (TTDE) in children with Kawasaki disease (KD). BACKGROUND Doppler-derived CFVR is a reliable marker predicting the presence of myocardial ischemia. METHODS We studied 49 patients (median age 11 years) with KD. The CFVR was calculated as the ratio of hyperemic to basal peak (peak CFVR) and mean (mean CFVR) diastolic flow velocities in the posterior descending coronary artery (PD) and left anterior descending coronary artery (LAD). The CFVR measurements by TTDE were compared with the results of coronary angiography, thallium-201 (Tl-201) single-photon emission computed tomography (SPECT), and intracoronary Doppler study. RESULTS The CFVR measurements by TTDE were obtained in 92 (94%) of 98 vessels of the PD and LAD in 49 study patients. Both peak and mean CFVRs for 21 stenotic vessels were significantly smaller than those for 35 normal vessels and for 20 vessels with aneurysmal lesions (p < 0.0001). Peak and mean CFVR <2.0 predicted significant coronary stenosis, as determined by coronary angiography, with sensitivities and specificities of 89% and 96% and 89% and 97%, respectively. Also, both peak and mean CFVRs were correlated with reversible perfusion defects on Tl-201 SPECT (agreement 80%; kappa 0.4). The correlation between peak and mean CFVRs determined by the TTDE and intracoronary Doppler studies in 36 vessels of 23 patients were 0.76 and 0.80, respectively. CONCLUSIONS The CFVR measured by TTDE predicts the presence of significant coronary stenosis of either the right coronary artery or LAD, as well as myocardial ischemia of these territories in children with KD.

The lower limit of the pulmonary artery index for the extracardiac Fontan circulation

OBJECTIVE In the era of the staged Fontan operation, small pulmonary artery index (<250 mm(2)/m(2)) has not affected the early or midterm results. The lower limit of pulmonary artery index, however, has not yet been determined. We created numeric models of the Fontan circulation to investigate the lower limit of the pulmonary artery size. METHODS The extracardiac Fontan geometries with pulmonary artery index, ranging from 50 to 200 mm(2)/m(2) with every 10-mm(2)/m(2) increase, were created from the postoperative angiographic data of 17 patients. The superior and inferior vena caval flow rates at rest and on 2 exercise levels (0.5 and 1.0 W/kg) were given by magnetic resonance imaging flow studies. Respiration-driven transient flow analysis was performed with a finite element solver. Energy loss and mean inferior vena caval pressure were obtained from the results. RESULTS Energy loss and mean inferior vena caval pressure were prominently increased in small pulmonary artery index models, especially during exercise. The pulmonary artery indices sufficient for mean inferior vena caval pressure less than 17 mm Hg were 80 mm(2)/m(2) at rest, 100 mm(2)/m(2) during 0.5-W/kg exercise, and 110 mm(2)/m(2) during 1.0-W/kg exercise. With the increase of pulmonary arterial resistance, mean inferior vena caval pressure increased, but the flow pattern did not change. CONCLUSIONS A small pulmonary artery causes a high pressure gradient and a high energy loss. The lower limit of pulmonary artery index, considering the exercise tolerance, was 110 mm(2)/m(2).

Contributions of Respiration and Heartbeat to the Pulmonary Blood Flow in the Fontan Circulation

BACKGROUND In the Fontan circulation, driving forces with respiration, heartbeat, and lower limb muscle pump are relevant. However, the mechanics of these forces has not been proven, and their effects on the Fontan circulation remain unclear. METHODS We performed catheter examinations and measured pressure and flow velocity simultaneously in the bilateral pulmonary arteries of 12 Fontan patients 1 year after the operation. The pulmonary pressure and flow velocity data were decomposed into respiratory and heartbeat components by discrete Fourier analysis. We then calculated respiratory and cardiac wave intensity (WI) based on the respiratory and heartbeat components of pressure and flow velocity data. RESULTS Respiratory WI formed 2 negative peaks, a backward expansion wave during the inspiratory phase, and then a backward compression wave during the expiratory phase. In 2 phrenic nerve palsy cases and 1 case of a patient on a respirator, respiratory WI showed disturbed patterns and a negative pattern, respectively. Cardiac WI showed 2 or 4 negative peaks, the time phase of which matched that of the atrial contractions. CONCLUSIONS WI analysis elucidated that inspiration acts as a sucking driving force and increases the pulmonary blood flow in the Fontan circulation. Respiratory complications compromise efficiency in the Fontan circulation. It was also revealed that the pulmonary blood flow was mutually dammed up and sucked in by increases and decreases in atrial pressure.

LONG-TERM FOLLOW-UP RESULTS OF PERCUTANEOUS CATHETER INTERVENTION FOR CORONARY ARTERY LESIONS AFTER KAWASAKI DISEASE: MULTICENTER COLLABORATIVE STUDY

INTRODUCTION: The long-term prognosis in patients with Kawasaki disease (KD) after percutaneous coronary intervention (PCI) remains unclear. OBJECTIVE: We sought to clarify the long-term results of PCI for KD. METHODS: Patients who developed coronary stenotic lesions caused by KD and were treated with PCI were investigated. Restenosis or obstruction was diagnosed when the stenosis was ≥75% according to coronary angiography or ischemic change was observed by myocardial perfusion imaging. RESULTS: A total of 55 stenotic lesions were reported in 49 patients in 5 institutions. The types of PCI included percutaneous transluminal coronary angioplasty (n = 22), stent implantation (n = 7), percutaneous transluminal coronary rotational ablation (PTCRA) (n = 22), and combination of PTCRA with stent implantation (n = 4). Median age at PCI was 14.5 years, and the median follow-up period in the PCI group was 6.3 years. of 55 stenotic lesions in the PCI group, 52 (95%) were dilated successfully by PCI. Immediate complications in the PCI group included neoaneurysm in 5 patients, transient bradycardia in 3 patients, and atrial fibrillation in 1 patient. Treatment for restenosis in the PCI group included re-PCI in 3 patients, coronary artery bypass grafting in 6 patients, and heart transplantation in 1 patient. No patient in the PCI group died. There was no difference in effectiveness among the 3 PCI devices (percutaneous transluminal coronary angioplasty versus stent implantation versus PTCRA: log-rank test, P = .3). CONCLUSIONS: PCI for KD can be accomplished and can be effective in the long-term.

Timing of Haemophilus influenzae type b vaccination after cardiac surgery

The best time for vaccination in infants with congenital heart disease (CHD) after cardiopulmonary bypass (CPB) surgery is unclear, but it is important to prevent Haemophilus influenzae type b (Hib) infection in infants with CHD after CPB surgery. To identify the best time for Hib vaccination in infants with CHD after CPB surgery, we investigated the immunological status, and the efficacy and safety of Hib vaccination after CPB surgery.