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.     

Proarrhythmia associated with cisapride in children

BACKGROUND: Cisapride is a prokinetic agent that facilitates gastrointestinal motility and is widely used for the treatment of gastroesophageal reflux disease (GERD) in adults and children. However, reports of ventricular proarrhythmia have been noted in patients taking cisapride, particularly in conjunction with other drugs that may inhibit hepatic metabolism of cisapride via the cytochrome P450 3A4 system. OBJECTIVE: We designed a prospective, blinded study to evaluate the effect of cisapride on ventricular repolarization in children with GERD. METHODS: We analyzed the electrocardiograms (ECGs) from 35 children (age 0.4 to 18 years, mean 5.2 years) including measurement of the resting QT interval (QTc), JT interval (JTc), as well as QT and JT interlead dispersion markers. Data from these patients were compared with ECGs from a control group of 1000 normal children. RESULTS: Eleven (31%) of 35 patients receiving cisapride had a prolonged QTc (> or = 450 ms). The JTc was prolonged > or = 360 ms in 16 of 35 patients (46%). The mean QTc in the cisapride group was 428 +/- 35 ms and mean JTc was 336 +/- 35 ms. An increased QT or JT dispersion (> 70 ms) was seen in only 3 of 35 children. Of the 11 children with QTc prolongation, 2 had documented torsades de pointes ventricular tachycardia. Both patients were taking cisapride concomitantly with a macrolide antibiotic. All other patients were treated with either cisapride alone or in conjunction with other GERD agents, such as ranitidine or omeprazole. CONCLUSIONS: Cisapride may cause prolongation of ventricular repolarization in children. There does not appear to be increased heterogeneity of repolarization or delayed depolarization in this small sample. The proarrhythmia may be exacerbated by medications that inhibit cytochrome P450 3A4 hepatic metabolism, overdosage, or mechanisms that result in decreased serum clearance. ECG intervals should be monitored in children maintained on cisapride, particularly when used in combination with other known QT-prolonging medications.     

Autonomic nervous system functions in children with breath-holding spells and effects of iron deficiency

Aim: To analyse the activity of the autonomic nervous system during breath-holding spells, we assessed the ECG changes, including ventricular repolarization parameters before and during the spell. We also analysed the effects of iron deficiency on these ECG parameters. Methods: The study group consisted of 37 children with breath-holding spells (30 cyanotic, 7 pallid) (mean age±SD: 12.9±10.8 mo). Twenty-six healthy children (mean age±SD: 14.4±8.6 mo) served as a control group. All patients and controls had standard 12-lead simultaneous surface ECG. All patients had ECG recordings during at least one severe breath-holding spell obtained by “event recorder”. Traces obtained by “event recorder” were analysed in terms of mean heart rate and the frequency and duration of asystole during the spell. Results: Respiratory sinus arrhythmia on standard ECGs and asystole frequency during spells were higher in patients with pallid breath-holding spells. Patients with iron deficiency had a lower frequency of respiratory sinus arrhythmia and prolonged asystole time during the spell. There was no difference in terms of ventricular repolarization parameters (QT/QTc intervals and QT/QTc dispersions) between patients and controls and between patient subgroups (cyanotic versus pallid).

Conclusion: These results confirmed the presence of autonomic dysregulation in children with breath-holding spells. Iron deficiency may have an impact on this autonomic dysregulation. Ventricular repolarization was unaffected in patients with breath-holding spells.     

Corrected QT Interval in Children With Brain Death

Prolongation of the QT interval is a well-documented finding in adults with severe brain injury. However, QT prolongation has not been well documented in the pediatric population with brain injury. Our objective was to determine the range of QT intervals in children with the diagnosis of brain death, hypothesizing that the QT interval corrected for heart rate (QTc) is longer in this population than in a normal population. All previously healthy children (<18 years) dying in our hospital from 1995 to 2007 with a diagnosis of brain death and at least one electrocardiogram (ECG) with normal anatomy by echocardiogram were included. Admission details, past medical and family history, demographic data, and laboratory data were collected. The QT and preceding RR intervals from three sinus beats on a standard 12-lead ECG were measured. The QTc was calculated with the Bazett method, and the values were averaged. Thirty-seven patients met inclusion criteria. Five had event histories concerning for possible underlying rhythm disturbances; data analysis was performed with and without these patients. The QTc data were normally distributed. The mean (SD) QTc for the entire cohort was 452 (61) ms. Excluding the five patients, it was 449 (62) ms. On multivariate analysis, sex (QTc female < male) and hypokalemia were associated with QTc prolongation. QTc in children with brain death is normally distributed but significantly longer than QTc in normal children. Until rapid genetic testing for channelopathies is universally available, our findings suggest that potential pediatric cardiac donors with isolated prolongation of the QTc in this setting may be acceptable in the absence of other exclusionary criteria.     

Effects of cisapride on ventricular depolarization-repolarization and arrhythmia markers in infants

To study prospectively the effects of cisapride on ventricular repolarization, depolarization, and arrhythmia markers in neonates, we determined before and three days after starting cisapride (1 mg/kg/day): corrected QT interval (QTc) and QT dispersion (QTd) on standard ECGs, and duration of filtered QRS (fQRS) and of low amplitude (<40 microV) terminal signals (LAS40, ms) and root mean square of the last 40 ms (RMS40, microV) using high-gain signal-averaged ECG (SAECG). Twenty-four term and 11 preterm infants (gestational age 23-35 weeks) were studied at a median chronological age of 32 days. QTc and QTd were not different between term and preterm infants. Cisapride lengthened QTc (mean +/- SD; ms: 396.6 +/- 24.8 before vs. 417.0 +/- 35.2 after, p < 0.001). Three term and two preterm infants (5/35 = 14%; 95% CI: 5-30%) had a QTc >450 ms after cisapride. QTd after cisapride increased significantly in all infants with prolonged QTc. Filtered QRS, LAS40, and RMS40 before and after cisapride were within our normal values. We conclude that cisapride prolongs ventricular repolarization in neonates and infants without altering depolarization. Although no clinical arrhythmias were observed the dose of 0.8 mg/kg/day should not be exceeded.     

Long QTc interval complicating halofantrine therapy in 2 children with Plasmodium falciparum malaria]

Halofantrine has been shown to be very effective against multiple drug resistant falciparum malaria. It is usually administered in children at 24 mg/kg at six-hour intervals for three doses, and a second therapeutic course one week following the initial treatment is recommended. It is usually well tolerated. However, prolongation of the QT interval has been reported in adults receiving this drug for malaria. CASES REPORTS: Two children experienced a prolongation of the QTc interval while receiving halofantrine. The first child, aged two years, had a prolonged QTc interval (490 ms) six hours after the third administration, at the usual therapeutic dose. The second child, aged six years, had a normal QT interval (360 ms) after the first 24 mg/kg dose and had a prolonged QTc (450 ms) during the second course seven days later, 15 h after the last dose. In both cases, the QTc interval returned to normal values (below 440 ms) rapidly after the end of treatment. CONCLUSION: Cardiotoxic effects are felt to be dose-dependant and young children may be particularly at risk due to pharmacological and cardiac immaturity. Therefore, guidelines for drug administration should be followed (administration in a child with an empty stomach, drug not recommended in combination with drugs known to prolong the QTc interval) and monitoring ECG in pediatric patients may be justified. The modalities of the second course in children, which is recommended by the manufacturer to travellers from non-endemic areas, should also be discussed.     

Clarithromycin treatment and QT prolongation in childhood

The effect of clarithromycin on the QT interval was studied in a group of 28 children treated for respiratory tract infections. QTc was measured before and following 24 h of treatment. A modest (average 22 ms, 95% CI 14-30 ms) but significant QTc prolongation (p<0.001) was observed, with seven cases having a QTc >440 ms during treatment (including a single case with QTc >460 ms). CONCLUSION: Serial QTc measurements are necessary for early detection of children at risk for drug-induced arrhythmias.     

How accurately can QT interval be measured in newborn infants?

We determined inter- and intra-observer variability of measurements of QT and heart rate corrected QT (QTc) interval in newborn infants. In 55 newborns, a standard 12-lead electrocardiogram (ECG) with rhythm strip was analysed independently by three observers. QT and the preceding RR interval were measured in three different beats. The QTc interval was calculated using the Bazett formula (QTc = QT/RR). Observers repeated their measurements after the recruitment period blinded for their first reading. Inter- and intra-observer variability were determined using the Bland and Altman method. In total, 59 ECGs were recorded. Due to artifacts, six had to be excluded. A marked inter-observer variability was observed in the measurement of the QT and QTc interval. Important intra-observer variability was denoted, with differences up to 80 ms for QTc. Conclusion:mainly due to high heart rates, important inter- and intra-observer variability hampers a correct interpretation of the QT interval in newborn infants. We suggest not to rely on one single measurement and to apply different methods of measurement and a margin of safety when interpreting QT and heart rate corrected QT intervals in these age groups for making therapeutic decisions.Abbreviations ECG Electrocardiogram - ESPGHAN European Society for Pediatric Gastroenterology, Hepatology and Nutrition - QTc heart rate corrected QT interval     

Effect of oral potassium supplementation on QT dispersion in anorexia nervosa

The aim of this study was to evaluate the degree of QT dispersion in a group of young women with anorexia nervosa and its changes after oral potassium supplementation. Twenty-eight patients with self-induced starvation were matched with 20 thin and 20 normal-weight women (body mass index > or = 20). All participants underwent a complete clinical examination, including electrocardiogram (ECG) for QT interval measurements. QT dispersion was defined as the difference between the longest and the shortest QT interval occurring in the 12-lead ECG. QT dispersion was corrected (QTc) with Bazett's formula. Anorexic patients were later allocated two subgroups of 14 to receive or not to receive potassium aspartate (2 vials K-Flebo d(-1) = 60 mEq d(-1), per os). ECG was repeated in both the subgroups of anorexic patients after 4 wk. QT dispersion was significantly greater in starving patients than in thin or normal-weight women (QT dispersion = 62.2 +/- 12.4 vs 33.4 +/- 7.1 or 31.7 +/- 6.3ms; QTc dispersion = 56.5 +/- 12 vs 34 +/- 9.1 or 33.2 +/- 11 ms, p < 0.001). After 4 wk, anorexic women treated with oral potassium aspartate supplementation, compared with untreated patients. showed an increased kalaemia (4.21 +/- 0.16 vs 3.91 +/- 0.32 mmol 1(-1), p < 0.05) and a significant reduction in the QT interval dispersion (QT dispersion = 44.2 +/- 8.1 vs 63.2 +/- 9.1 ms, QTc dispersion = 41.3 +/- 9.7 vs 57.4 +/- 9 ms, p < 0.001). CONCLUSION: Patients with anorexia nervosa have greater QT dispersion than constitutionally thin and normal-weight women, and oral potassium supplementation tends to reduce it. This suggests that the reduction in the pool of potassium may be the critical factor inducing the enhancement of the QT dispersion in anorexia nervosa.     

24-hour electrocardiogram before and during cisapride treatment in neonates and infants

We studied prospectively the effects of cisapride on heart rate and rhythm using standard ECG and 24-hour ECG recordings in term and preterm neonates and infants. We studied subjects with gastroesophageal reflux disease (apparent life-threatening events, apneas, bradycardias) before and 3 days after starting cisapride (0.8 mg/kg/day in 4 doses). We performed standard ECGs for determination of corrected Q-T interval (QTc) and Q-T dispersion (QTd) and 24-hour ECG recordings for analysis of heart rate, heart rate variability, and heart rhythm. Fourteen term and 17 preterm subjects (gestational age range 28-36 weeks) were studied at a median chronological age of 29 (range 3-132) days. Cisapride significantly increased the QTc in preterm infants (before vs. after: 408 +/- 7 vs. 433 +/- 7 ms, p = 0.001). Two preterm and 1 term infant had a QTc >450 ms before cisapride. Four preterm (4/15 = 27%) and 2 term (2/13 = 15%) subjects had a QTc >450 ms on cisapride. After cisapride the QTd remained normal, and no relevant arrhythmias were documented on Holter recordings. Cisapride significantly decreased peak and mean heart rates of all study subjects without affecting the heart rate variability, while it increased the minimal heart rate of preterm infants only (before vs. after: 66 +/- 5 vs. 78 +/- 5 bpm, p = 0.02). The maximally measured R-R intervals (pauses) decreased after cisapride in preterm infants (before vs. after: 1.33 +/- 0.2 s vs. 1.05 +/- 0.2 s, p = 0.04). Although cisapride did cause a significant prolongation of the ventricular action potential duration in preterm infants, the QTd remained unaffected, and no clinically relevant arrhythmias were documented in this small sample. On the other hand, cisapride had a direct lowering effect on the maximal and mean heart rates of both term and preterm infants, while the drug increased the minimal heart rate and reduced the severity of bradycardia episodes in preterm infants.     

QTc interval prolongation and QTc dispersion in children and adolescents with type 1 diabetes

OBJECTIVES: To evaluate whether QT interval, QT interval corrected for heart rate (QTc), and QTc dispersion changes are already present in children and adolescents with diabetes. STUDY DESIGN: QT interval, QTc, and QTc dispersion were measured on a 12-lead surface electrocardiogram in 60 children and adolescents with stable type 1 diabetes and in 63 sex- and age-matched control subjects. Differences were evaluated by using the Kolmogorov-Smirnov Z test. The number of patients with QTc > 440 ms was compared in the two groups. The possible influence of age, sex, diabetes duration, and glycosylated hemoglobin (HbA(1c)) was examined by using Spearman correlation analysis. RESULTS: Diabetic children had significantly longer QTc intervals and a significantly larger QTc dispersion. The number of individuals with a QTc >440 ms was significantly higher in the diabetic group (14/60) than in the control group (2/63). The effect of age on R-R interval and QTc dispersion in healthy children was less pronounced in children with diabetes. HbA(1C) values did not significantly correlate with any of the parameters. CONCLUSIONS: QTc prolongation and a larger QTc dispersion are already present in a significant proportion of children and adolescents with diabetes.     

Measures of cardiac repolarization and body position in infants

Sudden Infant Death Syndrome (SIDS) is the most common cause of death in children between 1 and 6 months of age. Recent data suggest that a prolonged QTc interval on the 12-lead electrocardiogram (ECG) is associated with SIDS. Prone body position during sleep is also known to be a risk factor for SIDS; this has prompted the American Academy of Pediatrics to promote the "Back to Sleep" campaign. We postulated that the QTc interval in infants might change as a function of body position, linking the observations relating body position and QTc interval to SIDS. We recorded ECGs in a group of infants in both the supine and prone position to determine if the QTc interval and QT dispersion differ between the 2 positions. Forty-seven standard 12-lead EGGs and high-amplitude, rapid-sweep 12-lead EGGs were performed on 45 healthy infants (mean age 26 +/- 40 days) in both the supine and prone positions. The infants were asleep in a quiet, restful state. The ECGs were reviewed by 2 investigators blinded to the position of the infants during recording. Measurements included the average QTc interval (using Bazett's correction) and QT dispersion (the difference between the longest and the shortest QT intervals on a standard 12-lead EKG). The study was designed to detect a 3% difference in QTc interval with 80% power and alpha = 0.05. All subjects had telephone or clinical follow-up at 1 year. The average QTc interval was 403 +/- 20 milliseconds (msec) in the supine position and 405 +/- 27 msec in the prone position (p = NS). The QT dispersion was 20 +/- 12 msec in the supine position and 22 +/- 13 msec in the prone position (p = NS). One infant in the study group died of SIDS at the age of 3 months. The EGG of this patient revealed a QTc interval of 382 msec in the supine position and 407 msec in the prone position; the QT dispersion was 34 msec in the supine position and 34 msec in the prone position. We found no difference in QTc interval or QT dispersion as a function of body position in healthy infants resting quietly. Prolongation of the QTc interval is unlikely to explain the increased risk for SIDS associated with prone body position in the general population of healthy infants, unless patients with long QT syndrome are somehow more influenced by body position than normal patients are.     

QTc interval prolongation in children with Turner syndrome: the results of exercise testing and 24-h ECG

Background  Turner syndrome (TS) is the most common sex chromosome abnormality in females. Recently, a prolongation of the rate-corrected QT (QTc) interval in the electrocardiogram (ECG) of TS patients has been reported. A prolonged QTc interval has been correlated to an increased risk for sudden cardiac death, and medical treatment is warranted in patients with congenital long QT syndrome (LQTS). Additionally, several drugs of common use are contraindicated in LQTS because of their effects on myocardial repolarization. The importance of the QTc prolongation in TS patients is not known at present. Materials and methods  Eighteen TS patients with a prolonged QTc interval (group 1) and 11 TS patients with a normal QTc interval (group 2) (mean age 12.6±3.1 vs. 11.8±2.1 years, respectively) were tested. The QTc interval was calculated during exercise testing and during 24-h ECG recordings. Results  None of the patients experienced adverse cardiac events during the tests. The mean QTc interval decreased from 0.467 to 0.432 s in group 1 and from 0.432 to 0.412 s in group 2. During the 24-h ECG, the maximum QTc interval was significantly prolonged in group 1 (0.51 vs. 0.465 s, p<0.05, respectively). We conclude that exercise testing and 24-h ECG recording provide valuable information about the cardiac risk in the single TS patient with a prolonged QTc interval. This helps in counseling these girls, as clear therapeutic guidelines are currently lacking. All authors state that there is no conflict of interests.     

Effects of cisapride on ventricular repolarization in children

Life-threatening ventricular dysrhythmias mainly attributed to QTc prolongation have been reported in adults and children who were using cisapride, a prokinetic agent that facilitates gastrointestinal motility. Recent adult and paediatric case reports have suggested an association of malignant ventricular dysrhythmias with administration of cisapride in conjunction with drugs that inhibit its cytochrome P-450 metabolism. Therefore, to analyse the time- and dose-related effects of cisapride on ventricular repolarization, we prospectively studied infants and children receiving cisapride with no concomitant medications. Standard 12-lead resting ECGs were obtained from 38 patients (mean age: 6.6 +/- 4.4 y) before the first dose of cisapride (0.8-1.2 mg/kg/d) therapy, and 3 d, 7 d and 1 mo after the first dose of continuing cisapride therapy. The corrected QT interval (QTc), dispersion of QT and QTc (QTD, QTcD) were calculated. Patients were divided into two groups according to dose of cisapride: Group 1 (n = 22) (0.8 mg/kg/d), Group 2 (n = 16) (1.2 mg/ kg/d). Data obtained from these patients were compared with a control group consisting of 372 normal children. No clinical adverse effects such as palpitations, presyncope or syncope were noted during the study. Baseline QTc, QTD and QTcD measurements of the study group were not different from those of the control group. Mean QTc values of the study group on days 7 and 30 of cisapride therapy were found to be significantly higher than those of the control group (p < 0.001 and <0.0001, respectively). Mean QTc values of the study group on days 7 and 30 of therapy were also significantly higher than those of baseline value (p < 0.01 and <0.001, respectively). Mean QTD and mean QTcD values that were recorded throughout the cisapride treatment in the study group were not found to be different from the baseline values and the values of the controls. Mean QTD and QTcD were also not found to be different between Groups 1 and 2. However, mean QTc was found to be more significantly increased from baseline at the first month of therapy in Group 2 (p < 0.05). The results of this study suggest that cisapride treatment cause prolongation of ventricular repolarization without causing increased heterogeneity of repolarization (QT dispersion). However, the clinical significance of this effect is unclear, because all the patients in this study group remained asymptomatic, without signs of dysrhythmia.     

Increased QT dispersion in epileptic children

AIM: Epilepsy is a common paroxysmal disorder in childhood. Tachyarrhythmia, bradyarrhythmia, asystole, atrioventricular block, ventricular fibrillation or sudden death may occur during seizures. Mutations of ion-channel coding genes are found in patients with idiopathic or cryptogenic epilepsy. The ion channels also play a role in arrhythmogenesis. QT dispersion is a non-invasive method for assessment of regional repolarization differences within the myocardial tissue. This study investigated QT and QTc dispersion (QTcd) and the risk of dysrhythmia in epileptic children. METHODS: The first group included 28 patients with newly diagnosed epilepsy and not taking antiepileptic treatment (range 10 mo to 15 y, mean +/- SD 6.86 +/- 3.92 y), the second group included 34 patients taking antiepileptic treatment (range 1-14 y, mean +/- SD 7.51 +/- 3.68 y) and the control group included 52 healthy children (range 4 mo to 15 y, mean +/- SD 6.94 +/- 3.92 y). Twelve-lead ECGs were obtained and heart rate, RR interval, P wave amplitude and duration, PR interval, QRS duration, QRS axis and QT intervals were measured, and QTc, QTd, QTcd were calculated in all subjects. The measurements were repeated in the first group under antiepileptic treatment. RESULTS: While no significant difference in terms of heart rate, RR interval, P wave amplitude and duration, PR interval, QRS duration, QRS axis, QT intervals or QTc intervals was found, QTd and QTcd values were significantly increased in epileptic children compared with the control group. QTd was 58.1 +/- 13.4 ms and 35.9 +/- 9.3 ms and QTcd was 91.0 +/- 22.9 and 68.6 +/- 18.0ms in patients and controls, respectively. Antiepileptic treatment did not affect QT dispersion. CONCLUSION: QT dispersion is increased in epileptic children. Further investigation is needed to reveal the pathogenesis of myocardial repolarization abnormalities in epileptic patients.     

A missense mutation (G604S) in the S5/pore region of <Emphasis Type="Italic">HERG</Emphasis> causes long QT syndrome in a Chinese family with a high incidence of sudden unexpected death

Long QT syndrome (LQTS) is characterized by abnormalities in cardiac repolarization that lead to prolongation of the electrocardiographic (ECG) QT interval. Mutations in the human ether-a-go-go-related gene (HERG, KCNH2) cause the chromosome 7-linked LQT2 form of congenital LQTS, which is characterized by a prolonged QT interval and a bifid T-wave with an increased susceptibility to life-threatening cardiac arrhythmias, especially in children. We describe the genotypic and phenotypic pedigree of a large Chinese family (n = 36) in which 11 members were diagnosed with LQTS on the basis of typical ECG patterns for LQT2. Symptomatic syncopal episodes appeared in seven members of this family at a young age; an additional four members had died suddenly at ages of 18, 19, 24 and 70 years, respectively. Screening for SCN5A and HERG candidate genes identified a heterozygous missense mutation 1810G→A in exon 7 of HERG that leads to the substitution of the amino acid glycine by serine (G604S); this mutation was located in the S5/pore region of the HERG protein and was associated with a malignant phenotype. Ten of the family members carrying the mutation showed a prolongation of the corrected QT interval (QTc), and seven of these had experienced multiple syncopal episodes. The retrospective examination of documented ECG records revealed that one family member who had died suddenly also had a prolonged QT interval. This study is the first to demonstrate a close correlation between clinical phenotype and genotype with a 100% penetrance based on the pedigree of a Chinese family with LQT2. Yanmin Zhang and Nan Zhou contributed equally to this investigation.     

Electrocardiographic findings after 5-HT3 receptor antagonists and chemotherapy in children with cancer

BACKGROUND: The antiemetic efficacy of serotonin-type 3 (5-HT3) receptor antagonists has been found to be superior to older antiemetic drugs in cancer patients. Following the administration of these agents, changes in ECG parameters and increased or decreased heart rates have been demonstrated, but there is no sufficient data in children with cancer who are treated with cytotoxic agents. The objective of this study is to evaluate the ECG changes after administration of 5-HT3 receptor antagonists and chemotherapeutic agents in children with cancer. PROCEDURE: Thirty-eight patients with an age range between 2 and 19 years receiving chemotherapy for solid tumors were included in the study. The patients received 5-HT3 receptor antagonists 30 min before antineoplastic agents in 83 chemotherapy days. Antiemetic therapy consisted of ondansetron in 43 and granisetron in 40 chemotherapy days. Twelve-leads ECGs were obtained four times at the first day of each chemotherapy: just before 30, 90 min, and 24 hr after 5-HT3 receptor antagonists were given. Rate, rhythm, PR interval, QRS duration, ST segment, the shortest (QTca) and the longest (QTcb) QTc intervals with QTc dispersion (QTcd) were all evaluated. RESULTS: We found a significant shortening of the PR interval and QRS complex durations in the granisetron group at 90th min and at 24th hr, respectively. Also, granisetron infusion caused a significant prolongation of the QTca interval at 90 min. CONCLUSION: Although we observed minor ECG changes after 5-HT3 receptor antagonists and chemotherapy, neither dangerous rhythm disturbances nor serious ECG changes were seen.     

Reproducibility of corrected QT interval in pediatric genotyped long QT syndrome

Reproducibility of corrected QT interval (QTc), especially QTc after exercise, has not been thoroughly investigated. We reviewed charts of pediatric patients who underwent treadmill‐exercise stress testing without medication multiple times within 1 year. In patients with long‐QT syndrome (LQTS; n = 22), the discrepancy in QTc between two treadmill exercise stress tests using Fridericia's formula was 14 ± 12 ms at rest, 13 ± 12 ms 4 min after exercise, with a maximum of 14 ± 12 ms after exercise. There was no statistically significant difference in QTc between the two tests. Intraclass correlation coefficients (ICC) were 0.84, 0.85, and 0.85, respectively. In controls (n = 13), the discrepancy in QTc was 18 ± 12 ms at rest, 14 ± 7 ms 4 min after exercise, with a maximum of 14 ± 9 ms after exercise. There was no significant difference in QTc between the two tests. ICC were 0.78, 0.80, and 0.80, respectively. QTc calculated using Bazett's formula also showed high reproducibility. Reproducibility of QTc in children is high at rest and after exercise.     

Nerve Growth Factor Plasma Levels and Ventricular Repolarization in Rett Syndrome

Rett syndrome is a severe neurological developmental disorder. In this syndrome, the high incidence of sudden death is correlated with an alteration of ventricular repolarization. The purpose of this study was to evaluate plasmatic levels of nerve growth factor (NGF) in Rett patients with prolonged corrected QT (QTc) interval in comparison with those of Rett patients with normal QTc. We observed 23 female Rett patients (9.9 ± 4.7 years). NGF plasma levels and QTc interval were measured in all patients. Student t-test was performed for statistical analysis. NGF plasma levels were significantly lower in Rett patients with QTc interval prolongation (QTc > 0.44 sec) in comparison with Rett patients with a normal QTc interval (4.5 ± 4.5 vs 11 ± 8.3 pg/ml, p = 0.02). The alteration of NGF levels, observed in Rett patients with a long QTc interval, may explain the presence of an altered ventricular repolarization associated with a higher risk of cardiac arrhythmias.     

Practical attitude toward arrhythmia in the neonate and infant]

Arrhythmias in neonates and infants require a specific management due to the particular nature of the rhythm anomalies in children. Accurate diagnosis of the tachycardia is realised mainly by means of ECG recording and vagal manoeuvres. The nature of the tachycardia will determine management, therapy and prognosis. In neonates <3 months, supraventricular tachycardia due to Wolff-Parkinson-White syndrome represents 70% of all supraventricular tachycardias, which, after conversion by vagal manoeuvres, requires a preventive treatment by digoxine (10 y/kg/day tid). Neonatal flutter occurs in infants without structural heart disease. It has an excellent prognosis after conversion to sinus rhythm by transoesophageal pacing. Atrial tachycardia is less frequent but can induce a tachymyocardiopathy and often requires combined therapy including amiodarone. Long QT syndrome, clinically and genetically heterogeneous, is characterized by a prolongation of the QT interval (QTc > 440 ms) and a high risk of syncope and sudden death due to malignant ventricular arrhythmias. Beta-blockers significantly decrease cardiac events during follow-up.Congenital atrio-ventricular block is rare but potentially lethal in the first months of life in the absence of permanent pacing. The morbidity remains high during long term follow-up in unpaced children.