Effect of Age on QT Variability

Heart rate variability is influenced significantly by age. Recent studies have shown the utility of QT variability to study temporal repolarization lability, and increased QT variability is reportedly associated with sudden death. Because beat-to-beat QT interval variability appears to closely follow heart rate variability, this study investigated the relationship between age and QT variability. We obtained QT variability measures in 34 adults (22–55 years of age) and 15 children (6–14 years of age) using a novel algorithm to compute beat-to-beat QT intervals. QT variability corrected for mean QT interval was significantly inversely correlated with age. Coherence in the band of 0 to 0.5 Hz and high-frequency coherence (0.15–0.5 Hz) were also significantly inversely correlated with age. QT_vi (QT variability corrected for mean QT interval over heart rate variability corrected for mean heart rate) was not significantly related to age in supine posture during spontaneous or controlled breathing, whereas there was a modest negative relationship in standing posture. These findings suggest that coherence between QT and heart rate time series appears to be modulated by cardiac vagal activity.     

儿童血管迷走性晕厥QT间期离散度及心率变异性分析

目的探讨儿童血管迷走性晕厥（VVS）QT间期离散度（QTd）及心率变异性（HRV）的变化。方法采用日本光电9320K12导联同步心电图机及DeMar-K100动态心电图仪对52例VVS患儿及30例健康儿童的QTd及HRV进行测量。结果VVS患儿QTd、校正QT间期离散度和最长QT间期较对照组显著增大，差异具有显著性；直立倾斜试验（HUTT）阳性组和阴性组间QTd值比较差异无显著性。SDNN、SDANN及RMSSD病例组较对照组减小，且病例组SDNN、RMSSD与对照组相比差异有显著性；HUTT阳性组和阴性组间HRV差异无显著性。结论VVS的发病机制与交感神经和副交感神经调节存在障碍有关。HUTT作为诊断VVS的金标准，其阴性者不能除外VVS。QTd、HRV对于VVS患儿发生心肌缺血、心律失常等心血管事件具有一定的预测价值。     

Oxygen consumption in infants and children during heart catheterization

Oxygen consumption was measured in infants, children, and adolescents during diagnostic heart catheterizations. A total of 825 measurements of oxygen consumption (VO₂) was performed in 504 subjects using a semiopen hood system and a paramagnetic oxygen analyzer. In 256 subjects under 3 years of age, body dimensions and heart rate were found to be significant factors for oxygen consumption. The regression equation for both sexes was: VO₂/BSA (ml/min · m²) = 3.42 · height (cm) − 7.83 · weight (kg) + 0.38 · HR − 54.1 (r ²= 0.39, SD = 38.7), where BSA is body surface area and HR is heart rate. VO₂/BSA was significantly lower in infants less than 3 months of age (133 ± 33 ml/min · m²) compared with infants of 3–12 months (171 ± 37 ml/min · m²; p < 0.01). In 272 children aged 3 years and older and adolescents, gender was a significant factor in oxygen consumption together with BSA and HR. The regression line equation for males was VO₂/BSA (ml/min · m²) = 0.79 · HR − 7.4 · BSA(m²) + 108.1 (r ²= 0.45, SD = 34.2). The regression line equation for females is VO₂/BSA (ml/min · m²) = 0.77 · HR − 5.2 · BSA(m²) + 106.8 (r ²= 0.43, SD = 34.4). Hematocrit, systemic oxygen saturation, and blood pressure were not significant factors. The predictive value of nomograms for oxygen consumption is limited because of the large interindividual variations not explained by differences in gender, body size, or simple hemodynamic variables. Preferably, oxygen consumption is measured; but if nomograms for oxygen consumption are used for hemodynamic assessment, the wide confidence intervals should be considered.     

Current Concepts in Long QT Syndrome

Sudden cardiac death occurs in the United States with an incidence of more than 300,000 persons per year. The underlying cause of death is commonly considered to be due to primary or secondary arrhythmias. In young persons in whom no structural heart disease can be identified, the long QT syndromes (LQTS) are commonly considered as likely causes. Multiple genes causing LQTS have been identified thus far, all of which encode cardiac ion channels. These include two potassium channel α subunits (KVLQT1 and HERG), two potassium channel β subunits (minK and MiRP1), and one sodium channel gene (SCN5A). The purpose of this review is to describe the current understanding of the molecular genetics of LQTS and the resultant phenotypes, particularly in young patients.     

Fetal Presentation of Congenital Long QT Syndrome

Thirty-two-week prenatal ultrasound revealed a fetal heart rate of 100 bpm with decreased variability on the heart rate tracing. Echocardiogram documented normal anatomy and sinus bradycardia. Newborn electrocardiogram revealed sinus rhythm at 100 bpm with a QTc of 0.657. Follow-up electrocardiogram revealed a QTc interval of 0.568, 2:1 atrioventricular block with a ventricular rate of 60 bpm, and ventricular ectopy. The infant received a pacemaker and beta-blocker therapy. Long QT syndrome should be in the differential diagnosis of the fetus with bradycardia and decreased heart rate variability in the absence of distress. Early diagnosis allowed for preventative care in the infant and identification of family members at risk.     

Perinatal manifestations of idiopathic long QT syndrome

A neonate who had presented with sustained irregular heart rate during labor was found to have QT prolongation and repetitive polymorphic ventricular tachycardia (torsades de pointes) postnatally. Propranolol and propafenone successfully controlled the ventricular arrhythmias. Follow-up electrocardiograms and Holter records show persistent QT prolongation, bizarre T waves, and intermittent episodes of T wave alternans. On propranolol monotherapy the boy is thriving and completely free of ventricular arrhythmias. In the rare case of long QT syndrome in the neonate, early detection and therapy are mandatory to prevent ventricular arrhythmias and sudden death.     

Parameters of iron deficiency in children with cyanotic congenital heart disease

A group of 67 children with cyanotic congenital heart disease (CCHD) were studied, and 35 were given iron treatment according to a regimen that gives iron to patients with a hematocrit (Hct) below 60%. The patients were categorized as iron-deficient and iron-sufficient according to their transferrin saturation and ferritin values. The pretreatment hemoglobin (Hb) and Hct values of the groups were similar. The mean Hct was nearly three times as much as the mean Hb in the iron-sufficient group and more than three times as much as the Hb in the iron-deficient group. Excessive erythrocytosis in the iron-deficient group was impressive. Mean corpuscular volume (MCV) values were below 72.7 fl in all of the iron-deficient patients. After treatment the Hb, Hct, transferrin saturation, and ferritin increased significantly in both groups, with the increments greater in the iron-deficient group. Increments in the erythrocyte (RBC) count were significant in the iron-sufficient group but insignificant in the iron-deficient one. Increments of MCV in the iron-deficient group were significant but insignificant in the iron-sufficient group. Our study demonstrated that prediction of Hb, RBC count, and MCV, measurements of which are easy and inexpensive and require little blood, can suffice for the diagnosis of iron deficiency in patients with CCHD without altering systemic perfusion.     

Autonomic Changes and Heart Rate Variability in Children with Neurocardiac Syncope

This study evaluated resting autonomic function and autonomic responses to head-up tilt-table testing in children who experienced neurocardiac syncope to determine whether predictable differences existed between these patients and normal volunteers. Neurocardiac syncope is a common cause of syncope in children. The mechanism, though related to abnormalities in autonomic function, has not been fully elucidated, particularly in pediatric patients. This study evaluated resting autonomic tone using noninvasive autonomic function tests (i.e., Valsalva, handgrip, and deep breathing) and 24-hour heart rate variability (HRV). In addition, heart rate and blood pressure were evaluated during head-up tilt examination. Values from patients who experienced neurocardiac syncope were compared to those from age-matched normal volunteers. No significant differences were noted during noninvasive testing. Some time domain HRV variables demonstrated a trend toward significant difference (p < 0.10). Tilt testing data were significantly different in sinus beat to sinus beat (RR) intervals between controls and syncope patients at 2, 5, and 10 minutes after tilting. In addition, significant differences were noted in RR interval and the standard deviation of RR interval 1 or 2 minutes prior to syncope when compared to controls at 5 and 10 minutes after tilting. Children with syncope exhibited abnormalities during tilt testing indicating an increased sympathetic or decreased parasympathetic tone, particularly prior to syncope. Some measures of HRV might constitute noninvasive parameters that correlate with the positive tilt table test.     

Prevalence of Idiopathic Long QT Syndrome in Children with Congenital Deafness

Long QT syndrome (LQTS) is characterized by prolongation of the QT interval associated with a high risk for syncope and sudden death. Jervell and Lange-Nielsen initially described LQTS in association with congenital sensorineural deafness. We have investigated the prevalence of this syndrome in a school for deaf children, evaluating by ECG 350 congenitally deaf children with an age range of 6–19 years. The corrected QT interval (QTc) was calculated by Bazett's formula. Eight children with a QTc interval >440 ms were further studied by cardiac examination, repeat ECGs (three times), Holter monitoring, echocardiography, and exercise testing. The families were assessed for a history of syncope and deafness and underwent ECG evaluations regarding lengthened QTc interval. Among these eight children only two girls aged 14 and 15 years were diagnosed as having LQTS according to Schwartz's criteria (0.57% of the 350 deaf children; 95% confidence intervals 0, ≤p≤ 0.013). The first patient had two major criteria (QTc 483 ms and a history of syncopal attack) and one minor criteron (congenital deafness); the second also had two major criteria (QTc 613 ms and family members with LQTS) and one minor criterion (congenital deafness). Prophylactic β-blocker therapy was started in these two patients to prevent sudden death. In conclusion, this syndrome should be sought in children with syncope or a family history of it, especially those with congenital deafness.     

Effects of Electrocardiography and Chest Radiography on the Accuracy of Preliminary Diagnosis of Common Congenital Cardiac Defects

The objective of this study was to compare the accuracy of the expert clinical examination for certain common cardiac defects with and without electrocardiogram (EKG) and chest radiogram (x-ray). The design of the study was a prospective, blinded comparison of diagnostic accuracy of the expert examination with and without EKG and x-ray, using echocardiography as the diagnostic standard. The setting of the study was the pediatric cardiology outpatient department. There were 749 outpatients with heart murmur under 21 years of age without prior echocardiography or pediatric cardiology consultation. The intervention was echocardiography as clinically indicated for evaluation of heart murmur of uncertain cause. Measurements were carried out using the incorporation of EKG and x-ray into multiple linear regression models to assess independent associations, if any, with the accuracy of clinical examination. Results were reported as the presence or absence of independent significant impact of availability of EKG and x-ray on examiner's diagnostic accuracy for innocent murmur, ventricular septal defect (VSD), pulmonary stenosis (PS), aortic valve disease, atrial septal defect (ASD), and patent ductus arteriosus. EKG enhanced detection of ASD and may have helped detect PS. X-ray enhanced detection of intermediate to large VSD. X-ray and EKG were otherwise without demonstrable independent advantage for defect-specific diagnosis. Routine use of one or both of these tests in the initial evaluation of heart murmur in the pediatric cardiology clinic should remain an option.     

Effects of Age and Respiration on Right Ventricular Diastolic Filling Patterns in Normal Children

Right ventricular diastolic filling was assessed in 88 normal Chinese children using Doppler echocardiographic interrogation of diastolic transtricuspid valve flow. Any influences of age and respiration on right ventricular diastolic filling were also investigated. The results showed that age-dependent differences were apparent for filling times, associated with the decrease in heart rate with increasing age. In addition, peak transtricuspid flow velocities were markedly greater in inspiration than in expiration, with corresponding increases in filling times and velocity–time integrals. The influence of age and respiration on transtricuspid flow parameters should be considered in the evaluation of right ventricular diastolic function by Doppler echocardiography. We believe that measurements should be standardized for respiratory phase and that right ventricular diastolic function parameters should be taken at end-inspiration and end-expiration, respectively.     

The effect of obesity, age, puberty and gender on resting metabolic rate in children and adolescents

During puberty fat-free mass (FFM) and fat mass (FM) change quickly and these changes are influenced by sex and obesity. Since it is not completely known how these changes affect resting metabolic rate (RMR), the aim of the present study was to investigate the effect of body composition, age, sex and pubertal development of postabsorptive RMR in 9.5- to 16.5-year-old obese and non-obese children. Postabsorptive RMR was measured in a sample of 371 pre- and postpubertal children comprising 193 males (116 non-obese and 77 obese) and 178 females (119 non-obese and 59 obese). RMR was assessed by indirect calorimetry using a ventilated hood system for 45 min after an overnight fast. Body composition (FFM and FM) was estimated from skinfold measurements. The mean (± SD) RMR was significantly (P < 0.001) lower in non-obese (males: 5600 ± 972 kJ/24h; females: 5112 ± 632 kJ/24h) than in obese (males: 7223 ± 1220 kJ/24h; females: 6665 ± 1106 kJ/24h) children. This difference became non-significant when RMR was adjusted for body composition (FFM + FM). However, the difference between the genders still remained significant (control male: 6118 ± 507, control female: 5652 ± 507, P < 0.001; obese male: 6256 ± 507, obese female: 5818 ± 507 kJ/24h, P < 0.001). The main determinant of RMR was FFM. In the whole cohort, FFM explained 79.8% of the variation in RMR, followed by age, gender and FM adding further 3.8%, 1.1% and 0.8% to the predictability of RMR, respectively. No significant contribution for study group (obese, non-obese), pubertal stage, or fat distribution was found in the regression for RMR. The adjusted value of RMR (for FFM and FM) slightly, but significantly (P < 0.01) decreased between the age of 10–16 years, demonstrating the important effect of age on RMR. Conclusions The resting metabolic rate of obese and control children is not different when adjusted for body composition. The main determinant of RMR is the fat-free mass, however, age, gender and fat mass are also significant factors. Pubertal development and fat distribution do not influence RMR independently from the changes in body composition. Received: 4 March 1996 / Accepted: 21 August 1996     

Normal Ranges of Heart Rate Variability During Infancy and Childhood

Heart rate variability is a noninvasive index of the neural activity of the heart. The present study examined heart rate variability indices in 210 infants and children aged 3 days to 14 years to obtain normal ranges for all age classes. Heart rate variability was measured by calculating mean RR interval over the length of the analysis, mean RR interval during quiet sleep, 5 time-domain (SDNN, SDNN-i, SDANN-i, r-MSSD, pNN50), and 4 frequency-domain (VLF, LF, HF, LF/HF ratio) indices. Our data show a significant positive correlation between all indices and the mean RR interval over the length of the analysis, except for the LF/HF ratio for which the correlation was binomial. A positive power correlation was also found between all parameters and age. The multiple correlation analysis confirmed the independent effect of age and mean RR interval on the heart rate variability. These data in a healthy pediatric population confirm a progressive maturation of the autonomic nervous system during childhood and may be utilized to examine the effects of underlying disease processes or therapeutic interventions on cardiac autonomic tone during infancy and childhood.     

Effects of low-dose dobutamine on left ventricular diastolic filling in children

To investigate the effects of dobutamine on the Doppler transmitral flow pattern in children with normal left ventricular function, Doppler echocardiography was used to measure the transmitral flow in 14 healthy children before and during infusion of dobutamine (5 μg/kg per minute). Cardiac output was measured by the thermodilution method, and stroke volume was calculated as the cardiac output divided by the heart rate. Dobutamine increased the peak velocity and flow velocity–time integral of early diastolic filling without changing those of atrial contraction and normalized peak velocity of early diastolic filling, suggesting an increase in left ventricular relaxation. Dobutamine increased the stroke volume and rate-corrected mean velocity of fiber shortening with reduced end-systolic wall stress, indicating an increase in left ventricular contractility. The percentage of increase in the flow velocity–time integral of early diastolic filling during dobutamine infusion tended to correlate with the increase in stroke volume (r= 0.67, p < 0.05) and with the decrease in end-systolic wall stress (r=−0.61, p < 0.05). Our results suggest that low-dose dobutamine increases left ventricular relaxation with enhanced systolic function. The observed decreased end-systolic wall stress might have caused enhanced relaxation characteristics with dobutamine.     

Relationship between age and heart rate variability in supine and standing postures: A study of spectral analysis of heart rate

Summary We compared heart rate variability measures of 11 normal children (4–12 years) to 23 normal adults (21–43 years) to study the effect of age on heart rate variability measures. Children had a significantly higher supine and standing heart rate and lower supine and standing systolic diastolic blood pressure. Children also had a significantly higher supine standard deviation of HR, supine low frequency (0.01–0.05 Hz) (p<0.005), supine high frequency (0.2–0.5 Hz) (p<0.001), and standing high frequency powers (p<0.005) compared to adults. The ratio of mid frequency (0.07–0.15 Hz) to high frequency power (0.2–0.5 Hz) upon standing was significantly lower in children (p<0.005). While there was a significant increase of the mid frequency power from supine to standing posture in the adult group (p<0.02), there was no such significant increase in children. There were also significant negative correlations between age and supine low frequency, mid frequency, and high frequency powers, and standing high frequency power. These findings illustrate a decrease of cholinergic and an increase of adrenergic modulation of heart rate variability with age (4–43 years).     

Neurally Mediated Syncope in Children: Results of Tilt Testing, Treatment, and Long-Term Follow-Up

Despite a great deal of literature concerning children with neurally mediated syncope (NMS) there is no clear standard of diagnosis or consistent approach to therapy. This report reviews our experience with tilt testing all patients who presented with syncope during a 3-year period. All patients referred for evaluation of syncope who underwent tilt testing were retrospectively reviewed. Follow-up was obtained at return visits or by telephone interview. Sixty patients were identified. The average age was 13.5 ± 3.0 years. Twenty-six patients (43%) had positive tilt tests. Follow-up was available for 56 patients. Twelve of these patients had causes other than NMS found for their symptoms. The remaining 44 patients all had histories consistent with NMS. Nineteen of these patients had positive tilt tests. All 44 patients reported either a decrease or no recurrence of syncope, and 41 patients reported a decrease or no recurrence of presyncopal symptoms. Recurrence of syncope or symptoms was not related to the results of the tilt test. Twenty-five of the 44 patients used conservative measures (extra fluids or supplemental salt) and only 3 patients were taking medications. The use of conservative measures or medications was not related to the tilt test results. Tilt testing has a high false-negative and false-positive rate and should not be used as the standard for identifying patients with NMS. The long-term follow-up of patients with NMS demonstrates that regardless of the results of the tilt test, almost all have improved or resolved symptoms with simple interventions.     

Respiratory syncytial virus infection in children with congenital heart disease: A review

This paper reviews recent changes in morbidity and mortality of respiratory syncytial virus (RSV) infection in infants with congenital heart disease. Mortality since the late 1970s has declined substantially, from approximately 37% to 3%. Although the frequency of admission to intensive care units has declined from approximately 60% to 30%, the frequency for mechanical ventilatory support has not changed significantly. Because mortality dropped prior to the widespread use of ribavirin, it is difficult to ascribe the improvement to this therapy. In infants with congenital heart disease (CHD), nosocomial infection remains a significant problem, accounting for approximately 33% of the RSV cases. Some authors report significant reductions in hospital-acquired RSV by use of gloves and gowns for contacts with infectious cases. Efforts at primary prevention have encountered problems with development of an RSV vaccine. Preliminary data from studies of passive immunization using immune globulins with high RSV antibody titers suggest that this therapy may reduce the severity of RSV infection in infants with serious heart disease.     

Cardiac troponin I and N-terminal pro-brain natriuretic peptide in umbilical artery blood in relation to fetal heart rate abnormalities during labor

The use of continuous fetal heart rate (FHR) recordings to monitor fetal well-being during labor is standard clinical practice in developed countries. Little is known about the relationship, if any, that exists between these FHR abnormalities and the fetal cardiac musculature and function. The aim of this study was to investigate umbilical artery serum levels of cardiac troponin I, a sensitive and specific marker of myocardial necrosis, and N-terminal pro-brain natriuretic peptide (pro-BNP), a sensitive marker of left ventricular dysfunction, in relation to FHR abnormalities. Umbilical artery blood samples were taken from 27 cases immediately after delivery of the infant. There was evidence of significant FHR abnormalities in 11 of these cases (group 2) and the FHR recording was normal in 16 cases (group 1). The mean N-terminal pro-BNP level in umbilical artery serum in group 2 was 413 fmol/L (SEM = 85) and in group 1 was 223 fmol/L (SEM = 28)(p= 0.022). There was no significant difference observed in cardiac troponin I levels between the two groups. Umbilical artery serum N-terminal pro-BNP is elevated in association with fetal heart rate abnormality in the late stage of labor. This finding suggests that some degree of cardiac compromise accompanies FHR abnormality.     

Congenital complete heart block in the fetus: hemodynamic features, antenatal treatment, and outcome in six cases

Congenital heart block (CHB) can result in intrauterine cardiac failure leading to fetal or neonatal loss. To establish perinatal hemodynamic factors which might predict adverse outcome, six fetuses with CHB diagnosed between 20 and 30 gestational weeks were examined by echocardiography at 2-week intervals. Neonatal morbidity and outcome in infancy are detailed. The fetuses showed a significant decrease in ventricular rate (VR) with advancing gestation (60 ± 7 vs 51 ± 4 beats/min, p= 0.03). Cardiac decompensation defined as hydrops or pericardial effusion was associated with VR of lower than 55 beats/min in two fetuses. Three mothers had a therapeutic trial with a sympathomimetic and digoxin. Salbutamol increased VR 10% in one of three fetuses treated. Digoxin decreased pericardial effusion in one hydropic fetus with autoimmune myocarditis. In this fetus, poor left ventricular fractional shortening (LVFS) was accompanied with high umbilical artery resistance index (RI). High amniotic fluid erythropoietin indicated severe hypoxia preceding death. Pacemaker was indicated in all the newborns. At the age of 2 weeks all the surviving infants had tricuspid regurgitation and a shunt through foramen ovale due to asynchronized atrioventricular contraction. During the 12-month follow-up two of five surviving infants had no symptoms. One had symptomatic neonatal lupus. Two infants had patent ductus arteriosus, one with dilated cardiomyopathy. In conclusion, poor fetal outcome was associated with low VR, low LVFS, and high RI. Despite early pacing, morbidity was high in infancy due to cardiomyopathy and associated heart defects. Regular echocardiographic monitoring during pregnancy and after delivery is required in order to optimize care and timing of any interventions.     

The Range of Normal Values of Cardiovascular Structures in Infants, Children, and Adolescents Measured by Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is a powerful diagnostic technique and research tool for assessment of congenital heart disease due to its ability to accurately assess anatomy, function, and flow in any orientation in the thorax. However, little data exist on normative reference values for cardiac structures, except in small study populations, and even fewer data exist for pediatric populations. In this review, MRI acquisition and analysis methods for assessment of aortic size, pulmonary artery size, and right and left ventricular function, volume, and mass are presented along with reference data obtained in pediatric populations by MRI. Where MRI data are not available, reference data obtained by echocardiography or angiography are included.