The electrophysiological index can effectively predict subsequent coronary artery aneurysm in children with Kawasaki disease.

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.

Effect of Hypothermia on Myocardial Depolarization and Repolarization in Neonates with Hypoxic-Ischemic Encephalopathy Due to Asphyxia.

Therapeutic hypothermia (TH) is effective for neonatal hypoxic-ischemic encephalopathy (HIE). The combination of abnormal myocardial repolarization and fatal arrhythmia in patients with accidental hypothermia has prompted clinical validation of the proarrhythmic potential of TH. However, to our knowledge, there have been few clinical studies on myocardial depolarization and repolarization abnormalities caused by TH in neonates. Therefore, we investigated the effects of TH on neonatal myocardial depolarization and repolarization by capturing the waveform changes in electrocardiograms (ECGs) associated with body temperature (BT) before and after TH. We included three neonates with HIE diagnosed at birth who were treated with TH in our hospital. The heart rate, RR interval, P wave duration, PR interval, QRS duration, QT interval, corrected QT (QTc) interval by Fridericia's formula, J point-T end (JT) interval, corrected JT (JTc) interval by Fridericia's formula, T peak-T end (Tpe) interval, Tpe/QT, and QRS/QTc were calculated retrospectively using an ECG. The correlations of ECG parameters recorded concurrently with 33 samples in which BT measurements were confirmed were performed. BT and heart rate were positively correlated (R: 0.589, p = 0.0003). BT was negatively correlated with Tpe/QT (R: - 0.470, p = 0.0058), the QTc interval (R: - 0.680, p < 0.0001), and the corrected JT interval (R: - 0.697, p < 0.0001). TH does not affect atrial or ventricular depolarization but prolongs the ventricular repolarization process in a temperature-dependent manner.

Myocardial repolarization time, J-point to T-peak and T-peak to T-end intervals, have different heart rate dependency and autonomic nerve interference in healthy prepubertal children.

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.

QT Variability Index is Correlated with Autonomic Nerve Activity in Healthy Children.

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 (r = 0.45, p < 0.001) and negative correlation with HF/(LF + HF) ratio (r = -0.429, p < 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.

Evaluation of perinatal autonomic development in infants using the QT/RR variability ratio.

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.

Glycocalyx Shedding is Enhanced by Age and Correlates with Increased Fluid Requirement in Patients with Major Burns.

BACKGROUND: Massive fluid shift after severe burn injury leads to edema and intravascular fluid loss that may result in burn-induced compartment syndrome (BICS) when corrected by aggressive fluid resuscitation. Factors causing this fluid shift remain unclear. Because glycocalyx regulates endothelial permeability, we hypothesized that glycocalyx shedding would increase fluid requirements in burn patients. This prospective cohort study aimed to identify relationships between shedding of the glycocalyx and fluid requirements after burn injury. METHODS: Patients aged more than 18 years with burn injury over more than 20% total body surface area (TBSA) were enrolled. Patient background factors including age, sex, burn size, and inhalation injury were recorded at patient enrollment. Serum syndecan-1, known as a biomarker of glycocalyx shedding, was serially measured on admission, day 1, days 3 to 5, around 1 and 2 weeks, and 1 month after the injury to observe postburn injury kinetics of syndecan-1. As biomarkers of endothelial damage, soluble thrombomodulin, antithrombin III, and plasminogen activator inhibitor-1 were also measured. We determined the relationship between syndecan-1 and initial 24-h fluid requirements and between syndecan-1 and morbidity/mortality. RESULTS: We enrolled 39 patients (median age, 55 years; median burn size, 35%TBSA): 16 developed BICS, and 10 patients died. Syndecan-1 level on admission was significantly higher than that in healthy volunteers and remained so. Syndecan-1 level on admission was associated with patient age (ρ = 0.50, P = 0.001) but not burn size (ρ = 0.08, P = 0.63), and antithrombin III level on admission was negatively associated with burn size (ρ = -0.48, P = 0.002). The syndecan-1 level on admission was significantly associated with fluid requirement (mL/kg) (ρ = 0.38, P = 0.017). After adjustment for age, sex, %TBSA, and inhalation injury, syndecan-1 was an independent parameter for the increase in fluid requirement (P = 0.04) and development of BICS (P = 0.03) by multivariable regression analysis. These findings suggested that glycocalyx shedding increased in an age-dependent manner, whereas antithrombin III decreased according to burn size. CONCLUSIONS: Glycocalyx shedding occurs soon after burn injury in an age-dependent manner. To reduce fluid-related complications such as BICS, new strategies to protect glycocalyx in burn patients are needed.

Acute intestinal damage following severe burn correlates with the development of multiple organ dysfunction syndrome: A prospective cohort study.

BACKGROUND: Severely burned patients occasionally suffer intestinal ischemia leading to a fatal outcome, and the gut is considered a "motor" driving the development of multiple organ failure. However, in clinical settings, it has been difficult to assess acute intestinal damage following burn and its consequence to patient outcome. Intestinal fatty acid binding protein (I-FABP) is a known biomarker for diagnosing intestinal ischemia/damage. This study aimed to assess the extent of intestinal damage using serial I-FABP measurements following severe burn and to clarify the association between intestinal damage and the development of organ dysfunctions. METHODS: Patients aged >15years old who suffered burn over 20% total body surface area (TBSA) were enrolled in this prospective cohort study. Patients with cardiac arrest on admission or who were transferred >24h after injury were excluded. Patients with chemical burn were also excluded. Burn size and Acute Physiology and Chronic Health Evaluation II (APACHE II) score were recorded at the time of patient enrollment. I-FABP was measured on admission and at 1, 4, 7, 14, and 30days following injury. Other biomarkers such as lactate, lactate dehydrogenase (LDH), creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase, amylase, and creatinine (Cre) were also measured at the same time points as I-FABP. We also evaluated the serial change in Sequential Organ Failure Assessment (SOFA) score. RESULTS: The study included 32 patients. Serum I-FABP level on the day of admission was significantly increased in the patients compared with healthy controls. Increased I-FABP levels were normalized at 4days after injury. The serum level of I-FABP on the day of admission correlated with %TBSA (III) and APACHE II score. A high I-FABP level on admission was associated with the subsequent development of multiple organ dysfunction. The increase in I-FABP level also correlated with increases of AST, LDH, and CK levels. CONCLUSIONS: Serum level of I-FABP on admission day does not correlate with burn size, but with the deep burn area. The gut might be a crucial target organ following severe burn, and gut damage could have an important role in the development of multiple organ dysfunction.

Heart failure exacerbation associated with newly developed atrioventricular dyssynchrony after chemical conversion to a sinus rhythm in a patient receiving cardiac resynchronization therapy.

A 58-year-old woman with chronic heart failure (CHF) received cardiac resynchronization-defibrillator (CRT-D) therapy without atrial lead implantation due to longstanding atrial fibrillation (AF). Three months after oral amiodarone therapy was initiated for the treatment of non-sustained ventricular tachycardia detected by the CRT-D device, the patient's heart failure symptoms worsened and 12-lead electrocardiography showed newly emerged p-waves with atrioventricular (AV) dissociation. Immediately after the device was upgraded to the DDD-biventricular pacemaker, the patient's heart failure symptoms and cardiac function dramatically improved, which suggests that AV dissociation has a much more negative impact on the cardiac function than AF in patients with CHF.

Ventricular repolarization lability in children with Kawasaki disease.

Kawasaki disease (KD) is an acute febrile disease of unknown etiology that develops in children and is sometimes accompanied by myocardial dysfunction and systemic vasculitis. However, myocardial repolarization lability has not yet been fully investigated. Thus, the objective of this study was to evaluate myocardial repolarization lability (QT variability index-QTVI) based on the body surface electrocardiograms in the acute and recovery phases. The subjects were 25 children with acute KD who were hospitalized for treatment. An equal number of age-matched healthy children were selected as controls. The RR-intervals and QT-intervals were measured based on a body surface electrocardiogram of 120 consecutive heartbeats to calculate the QTVI. The QTVI values were then compared with the acute and recovery phases. The relationships between blood biochemistry data and QTVI values were also examined. QTVI was significantly decreased from the acute phase to the recovery phase (P < 0.05) and then recovered to the same level as that of the control. QTVI in the acute phase showed a significant positive relationship with body temperature and C-reactive protein (P <0.05). QTVI was high in the acute phase and was correlated with an inflammatory reaction and became normalized during the recovery phase.

Beat-to-beat QT interval variability in children: normal and physiologic data.

BACKGROUND: QT interval variability provides information on ventricular vulnerability. However, QT interval variability in children has not been adequately evaluated. METHODS: One hundred seventy-three consecutive nursing infants and children (male-female, 106:67) up to school age with no intrinsic cardiac disease were included in this study, and they were categorized into 6 age-related groups. The QT variability index (QTVI) was calculated based on an electrocardiogram; and age-specific standard values, sex-specific classification, and a standard growth curve covering 0 to 7 years were constructed. RESULTS: The QTVI decreased in an age-dependent manner, reached constant values after school age, and exhibited no sex-specific differences in 6 age-related groups. CONCLUSIONS: Based on the age-dependent standardized QTVI values, it is possible to estimate the instability of ventricular repolarization in pediatric patients with better accuracy.