Masami Nagashima

Oxygen uptake efficiency slope: a new index of cardiorespiratory functional reserve derived from the relation between oxygen uptake and minute ventilation during incremental exercise.

OBJECTIVES We investigated the usefulness of a new variable, oxygen uptake efficiency slope (OUES), as a submaximal measure of cardiorespiratory functional reserve. The OUES is derived from the relation between oxygen uptake (Vo2 [ml/min]) and minute ventilation (VE [liters/min]) during incremental exercise and is determined by VO2 = a log VE + b, where a = OUES, which shows the effectiveness of Vo2. BACKGROUND Maximal oxygen uptake (VO2max) is effort dependent. There is no standard submaximal measurement of cardiorespiratory reserve that provides generally acceptable results. METHODS Exercise tests, following a standard Bruce protocol, were performed on a treadmill by 108 patients with heart disease and 36 normal volunteers. Expired gas was continuously analyzed. The OUES was calculated from data of the first 75%, 90% and 100% of exercise duration. We also determined the following submaximal variables: the ventilatory anaerobic threshold (VAT), the slope of the regression line of the minute ventilation-carbon dioxide production relation (VE-VCO2 slope) and the extrapolated maximal oxygen consumption (EMOC). We analyzed the relation of OUES and other submaximal variables against VO2max and examined the effects of submaximal exercise on OUES. RESULTS The correlation coefficient of the logarithmic curve-fitting model was 0.978 +/- 0.016 (mean +/- SD). The OUES and VO2max had a significant correlation (r = 0.941, p < 0.0001). The correlation between VO2max and OUES was stronger than that between VO2max and VAT, the VE-VCO2 slope or EMOC. The OUES values for 100% and 90% of exercise were not different from each other (at an alpha value of 0.05 and treatment effect of 170, the power of the test [1-beta] was 0.90); OUES for 75% of exercise was slightly lower (3.5%). CONCLUSIONS Our results suggest that OUES may provide an objective, effort-independent estimation of cardiorespiratory functional reserve that is related both to pulmonary dead space and to metabolic acidosis.

Analysis of heart rate variability demonstrates effects of development on vagal modulation of heart rate in healthy children

OBJECTIVES Analysis of heart rate variability (HRV) has been found to be a useful method of assessing cardiovascular autonomic control, but normal values for standard HRV measures in children have not been established. We analyzed HRV in 60 healthy children aged 3 to 15 years to determine normal values and to assess the effects of development on cardiac autonomic control with the use of ambulatory electrocardiographic monitoring. RESULTS The high-frequency (HF) component, an index of cardiac autonomic tone, increased significantly with age from 3 to 6 years (p < 0.01) and decreased with age from 6 to 15 years (p < 0.01), and the magnitude of HF correlated significantly with the R-R intervals. Thus the changes in cardiac autonomic tone could be described as a simple equation using age and heart rate. CONCLUSIONS We present normal values and changes in the cardiac autonomic system during childhood after HRV analysis, which could lead to a better understanding and treatment of cardiac disease in children.

High-dose gammaglobulin therapy for Kawasaki disease

To evaluate the effectiveness of gammaglobulin in decreasing the incidence of coronary artery lesions in Kawasaki disease, a randomized controlled study in 136 patients was conducted using high doses of gammaglobulin 400 mg/kg/d for 3 days plus aspirin 30 mg/kg/d (gammaglobulin group) and aspirin alone at the same dosage (aspirin group). The total febrile period and the duration of fever after treatment were significantly shorter in the gammaglobulin group than in the aspirin group (P less than 0.001). The incidence of coronary artery lesions and of coronary artery aneurysms was significantly lower in the gammaglobulin group than in the aspirin group up to 30 days after the onset of Kawasaki disease (P less than 0.01 and P less than 0.05, respectively). In 16 of 69 patients given gammaglobulin, fever persisted for longer than 3 days, and there was a higher incidence of coronary artery lesions among them. The effectiveness of high doses of gammaglobulin in preventing coronary artery lesions has been demonstrated, but the indications and the optimal dose of gammaglobulin remain to be determined.

Clinical characteristics and genetic background of congenital long-QT syndrome diagnosed in fetal, neonatal, and infantile life: a nationwide questionnaire survey in Japan.

Background—Data on the clinical presentation and genotype-phenotype correlation of patients with congenital long-QT syndrome (LQTS) diagnosed at perinatal through infantile period are limited. A nationwide survey was conducted to characterize how LQTS detected during those periods is different from that in childhood or adolescence. Methods and Results—Using questionnaires, 58 cases were registered from 33 institutions. Diagnosis (or suspicion) of LQTS was made during fetal life (n=18), the neonatal period (n=31, 18 of them at 0 to 2 days of life), and beyond the neonatal period (n=9). Clinical presentation of LQTS included sinus bradycardia (n=37), ventricular tachycardia/torsades de pointes (n=27), atrioventricular block (n=23), family history of LQTS (n=21), sudden cardiac death/aborted cardiac arrest (n=14), convulsion (n=5), syncope (n=5), and others. Genetic testing was available in 41 (71%) cases, and the genotype was confirmed in 29 (71%) cases, consisting of LQT1 (n=11), LQT2 (n=11), LQT3 (n=6), and LQT8 (n=1). Ventricular tachycardia/torsades de pointes and atrioventricular block were almost exclusively observed in patients with LQT2, LQT3, and LQT8, as well as in those with no known mutation. In LQT1 patients, clues to diagnosis were mostly sinus bradycardia or family history of LQTS. Sudden cardiac death/aborted cardiac arrest (n=14) was noted in 4 cases with no known mutations as well as in 4 genotyped cases, although the remaining 6 did not undergo genotyping. Their subsequent clinical course after aborted cardiac arrest was favorable with administration of &bgr;-blockers and mexiletine and with pacemaker implantation/implantable cardioverter-defibrillator. Conclusions—Patients with LQTS who showed life-threatening arrhythmias at perinatal periods were mostly those with LQT2, LQT3, or no known mutations. Independent of the genotype, aggressive intervention resulted in effective suppression of arrhythmias, with only 7 deaths recorded.

Oxygen uptake efficiency slope as a useful measure of cardiorespiratory functional reserve in adult cardiac patients.

Abstract In this study we aimed to elucidate the validity and usefulness of the oxygen uptake efficiency slope (OUES) in the evaluation of adult cardiac patients. Cardiopulmonary exercise tests were performed on a treadmill by 50 adult patients with chronic heart failure. The OUES was calculated from data for the first 75%, 90%, and 100% of exercise duration. The OUES is derived from the following equation: V˙O2=a× logV˙E+b, where V˙O2 is oxygen uptake (ml/kg/min), V˙E is minute ventilation (l/kg/min), and the constant “a” represents OUES. We also determined the ventilatory anaerobic threshold (VAT). The correlation coefficient of the logarithmic curve-fitting model was [mean (SD)] 0.986 (0.009). The OUES could be used to discriminate effectively between New York Heart Association functional classes (P < 0.001). OUES and maximum V˙O2 were significantly correlated (r=0.78, P < 0.01). Agreement between the OUES values for the first 90%, 75%, and 100% of the exercise was excellent (intraclass correlation coefficient = 0.99). Our results suggest that OUES is applicable to adult cardiac patients as an objective, effort-independent estimation of cardiorespiratory functional reserve.

Cardiac arrhythmias in healthy children revealed by 24-hour ambulatory ECG monitoring

SummaryAmbulatory electrocardiographic monitoring was performed on 360 healthy children, from newborn infants to junior high school students. They were divided into five groups by age: group A, 63 newborn infants on the first day of life; group B, 50 infants aged 1–11 months; group C, 53 kindergarten pupils aged 4–6 years; group D, 97 primary school pupils aged 9–12 years; and group E, 97 junior high school students aged 13–15 years.The maximal and minimal heart rates were significantly greater in infants than in older children. Sinus arrhythmia was recorded in every child. One boy in group E had an episode of sinus arrest for three seconds without any symptoms. First-degree and Wenckebach type second-degree atrioventricular blocks were not detected in group A and group B, but were most frequent in group E, especially during sleep. Supraventricular premature contractions (SVPCs) were the most common type of arrhythmia detected in this study. More than half of the children had at least one SVPC per 24-h monitoring period, and there were many children with frequent SVPCs in group E. The incidence of ventricular premature contractions (VPCs) in children of groups A and E was rather higher than in the other groups. Ventricular tachycardia was not recorded in any child except one newborn infant who had a couplet of VPCs without symptoms.Each group had different types and incidences of arrhythmias. There was a rising incidence of arrhythmias with advancing age, except in the neonatal period.

Role of the oxygen uptake efficiency slope in evaluating exercise tolerance

OBJECTIVE To investigate the interprotocol agreement of oxygen uptake efficiency slope (OUES). METHODS 16 Japanese children and adolescents (10 boys and six girls) underwent two sessions of maximal exercise testing according to the following two treadmill protocols: the standard Bruce protocol and the rapidly increasing staged (RIS) protocol. Maximal oxygen uptake (VO2max), the ventilatory anaerobic threshold (VAT), and the OUES were obtained from the gas analysis data. Agreement between the protocols was tested by means of the Bland-Altman method. RESULTS Interprotocol agreement was excellent for the OUES (limit of agreement, −18% to 17% of the mean value), slightly less good for VO2max (limit of agreement, −20% to 24% of the mean value), and poor for the VAT (limit of agreement, −31% to 31% of the mean value). CONCLUSION These results confirm the clinical usefulness of the OUES as a measure of evaluating exercise tolerance in the paediatric population.

Epidemiology of acute childhood encephalitis

The case records for 256 patients with acute encephalitis, including meningoencephalitis, acute encephalopathy and Reye syndrome, were obtained from 36 departments of pediatrics in large hospitals through questionnaires which were sent in 1990-92. The incidence rate per 100,000 child years was 3.3, and was more frequent in children aged 0-4 years (rate 6.6) than 5-15 years (rate 2.0), with statistical significance. The disease in the 105 etiologically diagnosed patients was due to measles virus (24), herpes simplex (21), rubella (24), and other agents (36), including two cases of human herpesvirus 6. A third of the infants with measles encephalitis were first seen at less than 18 months of age. Eighteen cases of rubella encephalitis occurred during an epidemic of rubella in Aichi Prefecture, 1987-88. The short-term outcome (mean length of follow-up: 2 years 3 months) of encephalitis was death in 20 cases (7.8%) and sequelae in 58 (24%). Eleven patients died within 7 days and five by the 8-14th day from onset. Thirty-six children had multiple residual impairments, including twelve who were severely handicapped. The prognosis for both life and sequelae was significantly poor for herpes simplex encephalitis in etiologically diagnosed patients. We stress the importance of an increase in the vaccination rate and the establishment of an early diagnostic system.

Ventilatory Control during Exercise in Normal Children

We investigated the relation between age and respiratory control during exercise in 80 children aged 6.4-17.6 y (42 male, age, 11.6 ± 3.3 y; body weight, 41.3 ± 14.7 kg; and 38 female, age, 12.6 ± 2.7 y; body weight, 42.5 ± 9.3 kg). Exercise tests were performed on a treadmill after a standard symptom-limited Bruce protocol. Data were analyzed separately for boys and girls. At rest and at peak exercise, the ratio of minute ventilation to carbon dioxide production(˙VE/˙VCO2), the ratio of effective alveolar ventilation to carbon dioxide production(˙VA/˙VCO2), the ratio of pulmonary dead space to tidal volume (Vd/V t), and arterial PCO2 (PaCO2) were not correlated with age. At the exercise intensity of ventilatory anaerobic threshold, the PaCO2 increased, and the ˙VA/˙VCO2 decreased, significantly with age, whereas the Vd/V t was not related to age. Linear regression analysis demonstrated that the slope of the relationship between ˙VE and ˙VCO2(Δ˙VE/Δ˙VCO2) and the slope of the relationship between ˙VA and ˙VCO2(Δ˙VA/Δ˙VCO2) decreased with age. There were no gender differences in the regression slopes and the intercepts of the relationships. Results show that younger children breathe more during exercise to eliminate a given amount of CO2 to keep PaCO2 set point slightly but significantly lower than older children. This age dependence must be considered in investigating ventilatory control during exercise in children.

Public access defibrillation improved the outcome after out-of-hospital cardiac arrest in school-age children: a nationwide, population-based, Utstein registry study in Japan.

Aims The purpose of this study was to determine whether implementation of public access defibrillation (PAD) improves the outcome after out-of-hospital cardiac arrest (OHCA) in school-age children at national level. Methods and results We conducted a prospective, nationwide, population-based Japanese Utstein registry study of consecutive OHCA cases in elementary and middle school children (7–15 years of age) who had a bystander-witnessed arrest of presumed cardiac origin during 2005–09 and received pre-hospital resuscitation by emergency responders. The primary endpoint was a favourable neurological outcome 1 month after an arrest. Among 230 eligible patients enrolled, 128 had ventricular fibrillation (VF) as an initial rhythm. Among these 128 patients, 29 (23%) children received a first shock by a bystander. Among these 29 patients, the proportion of the favourable neurological outcome after OHCA was 55%. During the study period, the proportion of patients initially shocked by a bystander among eligible patients increased from 2 to 21% (P = 0.002 for trend). The proportion of patients with a favourable neurological outcome after OHCA increased from 12 to 36% overall (P = 0.006). The collapse to defibrillation time was shorter in bystander-initiated defibrillation when compared with defibrillation by emergency responders (3.3 ± 3.7 vs. 12.9 ± 5.8 min, P < 0.001), and was independently associated with a favourable neurological outcome after OHCA [P = 0.03, odds ratio (OR) per 1 min increase, 0.90 (95% confidence interval 0.82–0.99)]. A non-family members witness was independently associated with VF as the initial rhythm [P < 0.001, OR 4.03 (2.08–7.80)]. Conclusion Implementation of PAD improved the outcome after OHCA in school-age children at national level in Japan.