畑 忠善

OBJECTIVES: The Gunma score is used to predict the severity of Kawasaki disease (KD), including coronary artery aneurysm (CAA) as a cardiac complication, in Japan. Additionally, the characteristic ratio of ventricular repolarization (T-peak to T-end interval to QT interval [Tp-e/QT]) on a surface electrocardiogram reflects myocardial inflammation. This study aimed to determine whether the Tp-e/QT can be used to predict CAA in children with KD. METHODS: We analyzed chest surface electrocardiograms of 112 children with KD before receiving intravenous immunoglobulin therapy using available software (QTD; Fukuda Denshi, Tokyo, Japan). RESULTS: The Tp-e/QT (lead V5) was positively correlated with the Gunma score (r=0.352, p<0.001). The Tp-e/QT was larger in patients with CAA (residual CAA at 1 month after onset) than in those without CAA (0.314±0.026 versus 0.253±0.044, p=0.003). A receiver operating characteristic curve analysis was performed to assess whether the Gunma score and Tp-e/QT could predict subsequent CAA. The area under the curve of the Gunma score was 0.719 with the cutoff set at 5 points. The area under the curve of the Tp-e/QT was 0.892 with a cutoff value of 0.299. The fit of the prediction models to the observed probability was tested by the Hosmer-Lemeshow test with calibration plots using Locally weighted scatterplot smoothing (LOESS) fit. The Gunma score (p=0.95) and Tp-e/QT (p=0.95) showed a good fit. CONCLUSIONS: The Tp-e/QT is a useful biomarker in predicting coronary aneurysm complications in KD.

OBJECTIVE: The JT interval of the myocardial repolarization time can be divided into Jpoint to T-peak interval (JTp) and T-peak to T-end interval (Tpe). It is well known that the JT interval is dependent on the heart rate, but little is known regarding heart rate dependence for JTp and Tpe. The aim of the present study was to clarify the heart rate dependence of JTp and Tpe and to elucidate the interference of autonomic nervous activity with these parameters. METHODS: We evaluated 50 prepubertal children (mean age: 6.4 ± 0.5 years; male:female, 22:28) without heart disease. JTp, Tpe, and the preceding RR intervals were measured using 120 consecutive beats (lead CM5). First, the relationships between the RR interval and JTp and Tpe were evaluated by Pearson's correlation coefficient. Second, to evaluate autonomic interference with JTp and Tpe, the degree of coherence between RR interval variability and JTp or Tpe variability was calculated using spectral analysis. RESULTS: Significant positive correlations were observed between the RR interval and JTp (y = 0.116x + 105.5; r = 0.594, p < 0.001) and between the RR interval and Tpe (y = 0.037x + 44.7; r = 0.432, p < 0.001). Tpe variability had a lower degree of coherence with RR interval variability (range: 0.039-0.5 Hz) than with JTp variability (0.401 [interquartile range, 0.352-0.460] vs. 0.593 [0.503-0.664], respectively; p < 0.001). CONCLUSIONS: Tpe had lower heart rate dependence and a lower degree of autonomic nervous interference than did JTp.

VITROS-5600 II装置を用いたSARS-CoV-2 Total抗体の試薬特性とその臨床的有用性について基礎的検討を行った。RT-PCR法で陰性患者3例、陽性患者3例の2種類のプール血清を作成し日内変動について確認した。その結果、検体1は陰性血清でその測定値は0.034±0.0057、変動係数(CV)16.62%、検体2は陽性血清で166.20±4.067、CV 2.45%であった。共存物質の影響について、ビリルビンF、ビリルビンC、ヘモグロビン、乳ビの影響は認められず、10倍希釈血清のCOI値はTotal抗体57.4、IgG抗体2.47で陽性と判定された。また、PCR陽性患者5例のプール血清を作成し原血清からカットオフ値(COI)付近まで希釈系列を作成しTotal抗体とIgG抗体を同時に測定した。その結果、IgG抗体がCOI(1.0)以下を示した時点でのTotal抗体値はCOI値を上回る反応を示していた。COVID-19戦略の一案として、PCR法とともに抗体測定方法の選択が重要であると考えられた。

Restrictive cardiomyopathy (RCM) is a rare myocardial disease with an impaired diastolic function and poor prognosis. Almost all RCM patients are reported to have abnormal P-waves due to atrial overloading. This study aimed to reveal the characteristics of the P-waves in RCM patients and to suggest the diagnostic index of RCM in children with a 12-lead electrocardiogram (ECG). We retrospectively investigated 17 ECGs of children with idiopathic RCM during the initial visit at 15 institutes in Japan between 1979 and 2013. The RCM group was divided into four groups based on the age (elementary school [ES] and junior high school [JHS] students) and inception of the diagnosis (abnormal ECG on school-heart-screening [e-RCM] and some cardiovascular symptoms [s-RCM]), the ES/e-RCM (n = 5), ES/s-RCM (n = 4), JHS/e-RCM (n = 4), and JHS/s-RCM (n = 4) groups. As an aged-match control group, school-heart-screening ECGs of 1st-grade ES students (16,770 students) and 1st-grade JHS students (18,126 students) from Kagoshima in 2016 were adopted. For a comparison between the groups, we used the effect size "Hedge's g" by calculating the mean and standard deviation of the two groups. An effect size of 0.8 (or above) had an overlap of 53% (or less). The effect sizes of the sum of the absolute values of the forward and backward amplitudes in lead V1 (P1 + P2 V1) was the largest, and the ES/e-RCM, ES/s-RCM, JHS/e-RCM, and JHS/s-RCM were 15.8, 22.1, 9.4, and 10.3, respectively. A P1 + P2 V1 > 200 μV was able to rule in all RCM patients, thus, we proposed 200 µV as the cutoff value for screening purposes. In conclusion, the P1 + P2 V1 in the school-heart-screening may be useful for detecting asymptomatic or early-stage RCM in school-age children.

BACKGROUND: T-wave inversion (TWI) is not considered useful for diagnosing pediatric arrhythmogenic right ventricular cardiomyopathy (ARVC), because right precordial TWI in ARVC resembles a normal juvenile pattern. OBJECTIVES: The aims of this study were to clarify the electrocardiographic (ECG) characteristics of pediatric ARVC to distinguish those patients from healthy children. METHODS: Between 1979 and 2017, 11 ARVC patients under 18 years old were registered and compared with school screening ECGs from 48,401 healthy children. RESULTS: The mean age at the first arrhythmic event or diagnosis was 13.3 ± 4.7 years. Nine patients were asymptomatic initially and were found by ECG screening, but 6 developed severe symptoms during the follow-up. Healthy children had a normal juvenile pattern, while ARVC children, especially symptomatic patients, had a significant tendency to have inferior and anterior TWI. The phenomenon of T-wave discontinuity (TWD) in which the TWI became deeper from V1 to V3 and suddenly turned positive in V5 was significantly more frequent in ARVC (60%) than healthy children (0.55%). Anterior TWI and TWD were also significantly more frequent in those who developed severe symptoms. The sensitivity and specificity of TWD were 60% (95% CI, 31-83%), and 99% (95% CI, 99-99%) to distinguish ARVC from healthy children, as well as 100% (95% CI, 71-100%) and 80% (95% CI, 51-80%), respectively, to predict severe symptoms in the future. CONCLUSIONS: The ECG is useful to distinguish ARVC children, even in the early phase. Anterior TWI and TWD could detect ARVC children and to predict the possible serious conditions.

Little is known whether 2-g/kg IVIG is necessary for older children with Kawasaki disease (KD), because they could have more complications and financial burden. The purpose of this study was to compare outcomes between high- and low-dose IVIG in KD children with higher body weight (25 kg or more), using a national inpatient database in Japan from 2010 to 2017. We identified those receiving 2-g/kg and 1-g/kg IVIG as an initial treatment. Outcomes included the proportions of coronary artery abnormality (CAA) formation, IVIG resistance, adverse effects, length of stay, and medical costs. A propensity score matching analysis was conducted to compare the outcomes between the groups. We identified 1332 patients with KD and created 4:1 propensity score-matched pairs between high- and low-dose IVIG groups. There were no significant differences in the proportions of CAA (5.3% vs. 4.1%; p = 0.587), IVIG resistance, and length of stay. Medical costs were significantly higher in the high-dose group than in the low-dose group (p < 0.001).Conclusion: No significant difference was shown between the high- and low-dose IVIG groups in the proportions of outcomes, while medical costs were higher in the high-dose group. Further studies are needed to ascertain the appropriate IVIG dose in older patients with KD. What is Known: • For treatments of Kawasaki disease at any age in the acute phase, 2-g/kg single-dose intravenous immunoglobulin and aspirin have been the most recommended to reduce fever early and prevent complications of coronary artery abnormalities. What is New: • There was no significant difference in outcomes between children with Kawasaki disease weighing ≥ 25 kg treated with high-dose or low-dose IVIG in terms of coronary artery abnormalities, IVIG resistance, adverse effects, and length of stay, except for medical costs.

<title>Abstract</title>The QT variability index (QTVI), which measures the instability of myocardial repolarization, is usually calculated from a single electrocardiogram (ECG) recording and can be easily applied in children. It is well known that frequency analysis of heart rate variability (HRV) can detect autonomic balance, but it is not clear whether QTVI is correlated with autonomic tone. Therefore, we evaluated the association between QTVI and HRV to elucidate whether QTVI is correlated with autonomic nerve activity. Apparently, healthy 320 children aged 0–7 years who visited Fujita Health University Hospital for heart checkup examinations were included. The RR and QT intervals of 60 continuous heart beats were measured, and the QTVI was calculated using the formula of Berger et al. Frequency analysis of HRV, including the QTVI analysis region, was conducted for 2 min and the ratio of low-frequency (LF) components to high-frequency (HF) components (LF/HF) and HF/(LF + HF) ratio was calculated as indicators of autonomic nerve activity. Then, the correlations between QTVI and these parameters were assessed. QTVI showed a significant positive correlation with LF/HF ratio (<italic>r</italic> = 0.45, <italic>p</italic> &lt; 0.001) and negative correlation with HF/(LF + HF) ratio (<italic>r</italic> = −0.429, <italic>p</italic> &lt; 0.001). These correlations remained after adjustment for sex and age. QTVI, which is calculated from non-invasive ECG and can detect abnormal myocardial repolarization, is significantly correlated with frequency analysis of HRV parameters. QTVI reflects autonomic nerve balance in children.

Background: Several immunochromatographic serological test kits have been developed to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies, but their relative performance and potential clinical utility is unclear. Methods: Three commercially available serological test kits were evaluated using 99 serum samples collected from 29 patients diagnosed with coronavirus disease 2019 (COVID-19) and 100 serum samples collected from 100 healthy volunteers in 2017 as negative controls. Results: The specificity of the IgM and IgG antibodies showed comparable results among the three immunochromatographic serological test kits. The specificity for IgM antibody was 98.0%, 98.0%, and 97.0%, and the specificity for IgG antibody was identical among the three kits (99.0%). The IgM antibody-positive rates of the three test kits for samples taken at the early stage of the disease (0-4 days after onset) were consistent with all three kits (18.2%); however, the IgM antibody-positive rates thereafter showed considerable differences among the kits, making it difficult to interpret the kinetics of IgM response against SARS-CoV-2. The IgG antibody-positive rates for samples taken after 13 days of onset were 100.0%, 97.6%, and 97.6%, respectively. Conclusion: There were large differences among the results of the three test kits. Only few cases showed positive results for IgM, suggesting that at least 2 of these kits used in this study were unsuitable for diagnosis of COVID-19. The IgG antibody was positive in almost all samples after 13 days of onset, suggesting that it may be useful for determining infections in the recent past.

OBJECTIVES: Development of the autonomic nervous system may play a role in myocardial repolarization lability in infants, but its relationship to repolarization abnormalities remains unclear. Thus, the aim of the present study was to evaluate the relationship between gestational age and ventricular repolarization lability using the variability ratio (VR). METHODS: Infants who underwent electrocardiography at a 1-month check-up were included (n=209; 125 males). Gestational age and the following four VR parameters at 1 month of age were compared: VR-I, SDQT/SDRR; VR-II, SDQT/rMSSD; VR-III, SDQTc/SDRR; and VR-IV, SDQTc/rMSSD; where SD, QTc, and rMSSD are standard deviation, QT interval corrected using Fridericia's formula, and root mean square difference of successive RR intervals, respectively. Twenty-eight preterm infants born at <37 weeks of gestation and 181 full-term infants were included. RESULTS: Significant correlations were observed between gestational age and VR-I, -III, and -IV (all p<0.05). All VR values were significantly higher in preterm infants compared with full-term infants (I: 0.54 vs 0.48, II: 1.15 vs 0.96, III: 0.88 vs 0.68, IV: 1.59 vs 1.39; median, all p<0.05). CONCLUSION: VR assessed at 1 month after birth was impaired in preterm infants, suggesting immaturity of their cardiac autonomic nervous system and ventricular myocardial repolarization.