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.     

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.     

Repolarization Abnormalities in Children with a Structurally Normal Heart and Ventricular Ectopy

In adults, increased QT dispersion has been shown to predict arrhythmic risk as well as risk of sudden death in several clinical settings. It is controversial whether QT and JT dispersion are increased in children with ventricular ectopy and a structurally normal heart. We studied two groups of children: 25 patients with ventricular ectopy and 25 healthy children as controls. Standard electrocardiograms were reviewed and dispersions of both corrected QT (QTc) and JT (JTc) intervals were compared. We conclude that QTc and JTc dispersions are significantly increased in children with ventricular ectopy compared to control subjects. This paper was presented as a poster at APS-SPR 2001, Baltimore.     

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.     

Assessment of Ventricular Repolarization in Deaf–Mute Children

The long QT syndrome is a congenital disease with frequent familial transmission, characterized primarily by prolongation of the QT interval and by the occurrence of life-threatening arrhythmias. The syndrome may be familial, with or without congenital deafness, or it may be idiopathic. We attempted to assess ventricular repolarization and to identify patients with the Jervell and Lange–Nielsen syndrome among 132 deaf–mute school children. Five deaf–mute subjects had Jervell and Lange–Nielsen syndrome. The deaf–mute subjects were divided into two subgroups according to the length of their QT intervals: group 1 included 5 cases with the long QT interval (>440 msec), and group 2 included 127 subjects with the normal QT interval (≤440 msec). Group 3 was composed of 96 control subjects. The mean QT, QTc, JT, and JTc intervals (418 ± 70, 500 ± 38, 302 ± 65, and 389 ± 36 msec, respectively) in group 1 were significantly longer than those of group 2 (344 ± 23, 408 ± 22, 249 ± 34, and 291 ± 28 msec, respectively) and group 3 (325 ± 11, 383 ± 26, 228 ± 36, and 269 ± 46 msec, respectively). The dispersion (d) values (QT-d, QTc-d, JT-d, and JTc-d; 63 ± 10, 73 ± 8, 60 ± 8, and 62 ± 11 msec, respectively) of group 1 were significantly longer than those of group 2 (49 ± 16, 43 ± 11, 48 ± 21, and 45 ± 18 msec, respectively) and group 3 (33 ± 13, 33 ± 14, 28 ± 16, and 27 ± 14 msec, respectively) at similar mean RR intervals. Also, the mean QT, QTc, JT, and JTc intervals and the dispersion values (QT-d, QTc-d, JT-d, and JTc-d) in group 2 were significantly longer than those of group 3 at similar mean RR intervals. Consequently, in this study, we determined that the deaf–mute children who did not meet the criteria for Jervell and Lange–Nielsen syndrome still had evidence of subtle derepolarization abnormalities evidenced by intermediate prolongation of QTc, JTc, and the corresponding measures of dispersion, and we believe an electrocardiogram examination of deaf–mute subjects will reveal this potentially life-threatening syndrome.     

Does cisapride influence cardiac rhythm? Results of a United States multicenter, double-blind, placebo-controlled pediatric study

BACKGROUND: Major concerns about serious cardiac side effects underlie the recent decision by the FDA and Janssen Pharmaceutica (Titusville, NJ) to make cisapride available only through a limited access program. Concerns have grown despite the fact that most instances of prolonged QTc and other ventricular arrhythmias occurred while the drug was used concomitantly with contraindicated drugs. This study sought to analyze electrocardiograms (ECGs) from a multicenter pediatric study and to identify abnormalities in QTc interval associated with cisapride use. METHODS: Children between 6 months and 4 years of age were enrolled if they manifested symptoms of gastroesophageal reflux not responding to medical therapy for at least 6 weeks. In 49 subjects, ECGs obtained before and after randomization to receive 0.2 mg/kg dose three times daily or placebo were reviewed independently and blindly by two pediatric cardiologists. Placebo and active drug groups were compared for QTc and for change in QTc from baseline values after 3 to 8 weeks of treatment. RESULTS: Mean QTc among patients taking the drug was 408+/-18 ms. None was higher than 450 ms. Change between baseline and subsequent QTc at 3 to 8 weeks of treatment was 2+/-20 ms. CONCLUSIONS: In our study group of children without underlying cardiac disease or electrolyte imbalance, cisapride was found to have no significant effect on cardiac electrical function compared with placebo. These results are consistent with the drug's record of exceedingly infrequent cardiac events. Because the availability of this prokinetic is threatened, its safety and the safety and efficacy of alternative treatment options (including surgery) should be studied further.     

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.     

Cisapride plasma levels and corrected QT interval in infants undergoing routine polysomnography

BACKGROUND: Reported QTc prolongation associated with cardiac arrhythmia in a small number of children undergoing cisapride therapy and lack of pharmacokinetic correlation provided the impetus for this prospective study. The authors evaluated the relation between cisapride plasma concentrations, the electrocardiographic QT interval, and cardiac rhythm in infants undergoing routine 8-hour polysomnography. METHODS: A total of 211 infants were enrolled: 84 (17 born prematurely) undergoing cisapride therapy for at least 4 days for suspected gastroesophageal reflux and 127 controls (10 born prematurely), aged between 1 week and 13.5 months. Infants underwent continuous bipolar limb lead I recording during routine 8-hour polysomnography. QT intervals and heart rate were measured at hourly intervals. The morning after polysomnography, 12-lead electrocardiography was performed (1 hour after cisapride administration). Cisapride plasma concentrations were determined immediately before and 1 to 2 hours after administration. Serum electrolyte concentrations were measured. RESULTS: The administered cisapride dose ranged from 0.35 to 1.55 (mean, 0.81, median 0.79) mg. kg-1. d-1. Cisapride plasma concentrations were significantly higher in infants younger than 3 months of age. Cisapride-treated infants younger than 3 months of age had longer QTc intervals compared with age-matched controls. Heart rate was similar for cisapride-treated and control infants. No arrhythmia or atrioventricular conduction abnormalities were observed. CONCLUSIONS: At comparable doses of cisapride and comparable plasma concentrations, the QTc was significantly higher in infants younger than 3 months of age. This confirms age-dependent cisapride pharmacokinetics in the first 10 to 12 weeks strongly correlated with changes in body weight and may also suggest an altered ability of infants younger than 3 months of age to metabolize cisapride. The clinical significance and risk of the increased QTc interval is unclear. Cisapride should be judiciously prescribed in infants younger than the age of 3 months and electrocardiography should be performed before and during therapy.     

Early post-convulsive prolongation of QT time in children

Aim: An important differential diagnosis of seizures in childhood is the long QT syndrome. Childhood epilepsy occurs about 400 times more often than long QT syndrome. We had observed children with slight post-convulsive prolongation of QT time more often than the reported incidence of long QT syndrome. We therefore conducted a prospective study to define the characteristics of post-convulsive prolongation of QT time in children. Methods: We investigated 30 consecutive infants and children (3 mo to 14 y) within 2 h after seizures. A follow-up ECG was obtained 1-9 d later. We also obtained ECGs from 30 healthy age- and gender-matched controls. We calculated the QT interval corrected for heart rate (QTc) by Bazett's formula in leads II, V5, V6, QT dispersion and the number of notched T waves. Results: We found a QTc interval of more than 440 ms in one or more leads in the first ECG in seven of 30 infants and children compared to 1 of 30 in the follow-up ECG (p=0.0003) and two of 30 in the healthy controls (p=0.14). Average QTc was higher for all leads in the first ECG. This was statistically significant in leads II (414 vs 402 ms, p=0.008), V5 (416 vs 404 ms, p=0.002) and V6 (415 vs 399 ms, p=0.001). Compared to healthy controls, QT dispersion was slightly larger in the early post-convulsive ECG (36 vs 31 ms, p=0.03). Notched T waves occurred more frequently in the early compared to the late post-convulsive ECGs (p=0.009).

Conclusion: Slight to moderate post-convulsive prolongation of the QT interval is not rare but transient in paediatric patients.     

The role of cisapride in the treatment of pediatric gastroesophageal reflux. The European Society of Paediatric Gastroenterology, Hepatology and Nutrition.

BACKGROUND: Cisapride is a gastrointestinal prokinetic agent that is used worldwide in the treatment of gastrointestinal motility-related disorders in premature infants, full-term infants, and children. Efficacy data suggest that it is the most effective commercially available prokinetic drug. METHODS: Because of recent concerns about safety, a critical and in-depth analysis of all reported adverse events was performed and resulted in the conclusions and recommendations that follow. RESULTS: Cisapride should only be administered to patients in whom the use of prokinetics is justified according to current medical knowledge. If cisapride is given to pediatric patients who can be considered healthy except for their gastrointestinal motility disorder, and the maximum dose does not exceed 0.8 mg/kg per day in 3 to 4 administrations of 0.2 mg/kg (not exceeding 40 mg/d), no special safety procedures regarding potential cardiac adverse events are recommended. However, if cisapride is prescribed for patients who are known to be or are suspected of being at increased risk for drug-associated increases in QTc interval, certain precautions are advisable. Such patients include those:(1) with a previous history of cardiac dysrhythmias, (2) receiving drugs known to inhibit the metabolism of cisapride and/or adversely affect ventricular repolarisation, (3) with immaturity and/or disease causing reduced cytochrome P450 3A4 activity, or (4) with electrolyte disturbances. In such patients, ECG monitoring to quantitate the QTc interval should be used before initiation of therapy and after 3 days of treatment to ascertain whether a cisapride-induced cardiac adverse effect is present. CONCLUSIONS: With rare exceptions, the total daily dose of cisapride should not exceed 0.8 mg/kg divided into 3 or 4 approximately equally spaced doses. If higher doses than this are given, the precautions above are advisable. In any patient in whom a prolonged QTc interval is found, the dose of cisapride should be reduced or the drug discontinued until the ECG normalizes. If the QTc interval returns to normal after withdrawal of cisapride, and the administration of cisapride is considered to be justified because of its efficacy and absence of alternative treatment options, cisapride can be restarted at half dose with control of the QTc interval. Unfortunately, at present, normal ranges of QTc interval in children are unknown. However, a critical analysis of the literature suggests that a duration of less than 450 milliseconds can be considered to be within the normal range and greater than 470 milliseconds as outside it.     

Cisapride and risk of cardiac complications

Cisapride is a prokinetic agent thought to be without severe side effects. Recently, rare cisapride-induced cardiotoxic effects (QT interval prolongation, ventricular arrhythmias) have been reported, raising questions about its safety. Some risk factors have been reported: overdosage of cisapride, association with some drugs inhibiting hepatic metabolism via the cytochrome P450 3A4 enzymatic system (such as azole antifungals, macrolide antibiotics, non sedating antihistamines), other pharmacological agents increasing the parasympathetic tone by raising the effect of cisapride (such as ranitidine and cimetidine), electrolyte abnormalities (such as low serum levels of calcium, potassium and magnesium in the blood), liver dysfunctions, congenital long QT syndrome, and infants born before 36 weeks' gestation, for three months after birth. Physicians, prescribing cisapride should pay attention to these risk factors, to avoid the possibility of a rare cardiac adverse effect.     

QT prolongation and minor head trauma: a report of two cases

QT prolongation is rarely seen after acute stress reactions such as burn injury and severe head trauma. Although pathophysiologic mechanism is not entirely clear, acute stress is thought to contribute to the inhomogeneity of ventricular repolarization and it is hypothesized that QTc dispersion increases with severity of acute stress conditions. In the present study, we report long QT syndrome in 2 patients with minor head trauma. Their QTc intervals, i.e. QT intervals corrected for heart rate by the standard Bazett formula, were found to be prolonged (545 and 450 ms, respectively) without creatine phosphokinase - MB elevation. These findings suggest that myocardial effects may occur as a result of probable catecholamine discharge, even if they are not at a level to affect creatine phosphokinase - MB values in minor head trauma. But these findings have not been supported by experimental data, for this reason we need a lot of study in order to confirm this hypothesis.     

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.     

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.     

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.     

Repolarization Patterns in Congenital Heart Disease

The aim of this study was to study the repolarization patterns in pediatric patients with cyanotic and acyanotic congenital heart diseases as prolonged QT indicates a myocardium at risk of ventricular arrhythmia. A cross-sectional case–control study included 50 patients with acyanotic congenital heart diseases and 50 patients with cyanotic congenital heart diseases who presented to Catheterization Unit of Cairo University Pediatric Hospital between March 2013 and June 2014. We included 50 healthy children as a control. For all the patients’ measurement of oxygen saturation, echocardiography and 12-lead electrocardiogram (ECG) were done and the corrected QT (QTc) was measured. The mean QTc was significantly higher in acyanotic congenital heart diseases with volume overload than in control: 0.426 versus 0.4 s (p = 0.009). Increased left ventricular end-diastolic dimension was significantly associated with QTc prolongation (p = 0.01). Early repolarization was higher in congenital heart diseases (18 % in acyanotic patient, 48 % in cyanotic patients) than in control 6 %. Decreased oxygen saturation was significantly associated with early repolarization (p = 0.01). Prolonged QTc was higher in acyanotic congenital heart diseases with volume overload and increased left ventricular end diastolic dimension was a significant association. Decreased oxygen saturation was a significant association.     

Pretransplant increases in left ventricular volume and mass are associated with QT prolongation during pediatric liver transplantation

Structural alterations in the cirrhotic heart may contribute to electromechanical abnormalities, represented by QT prolongation. The aim of this study was to investigate the changes in QTc according to the operative stage during pediatric LT and to identify which baseline echocardiographic parameters were associated with intraoperative QTc prolongation. Data were evaluated from 39 children undergoing LT for chronic liver disease (median age 9 months). In 19 patients (48.7%), baseline QTc was prolonged ≥440 ms (462 ± 19 ms). Through the period of post‐reperfusion, QTI, QTc, and JTI progressively increased, although values partially recovered toward the end of surgery. High LVMI (≥82.51 g/m²) was associated with baseline QTc ≥ 440 ms (OR = 1.034, P = .032). In the 5 minutes post‐reperfusion stage, marked QTc prolongation (defined as QTc ≥ 500 ms; n = 24, 61.5%) was significantly associated with high EDVI (OR = 1.060, P = .027) and SVI (OR = 1.075, P = .026). In children with chronic liver disease, increased ventricular volumes and mass may increase the risk of QTc prolongation during LT, suggesting that repolarization abnormalities might be contributed by structural changes characteristic of cirrhotic cardiomyopathy.     

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.     

Domperidone versus cisapride in the treatment of infant regurgitation and increased acid gastro-oesophageal reflux: a pilot study

Aim: Although domperidone is used frequently to treat infant regurgitation, efficacy data are scarce. Cisapride was previously used in the same indication.
Methods: Domperidone and cisapride were compared in an investigator-blinded, prospective comparative trial by evaluating (a) the frequency of regurgitation, (b) acid reflux and (c) cardiac side effects in infants regurgitating >4 times/day since >2 weeks and with reflux-associated symptoms of discomfort, after conservative treatment failure.
Results: Within the first treatment week, the frequency of regurgitation decreased in both groups, more rapidly in the cisapride group: the median regurgitation decreased from 6.22 to 3.50 in the cisapride group versus from 4.80 to 3.70 in the domperidone group. The decrease in regurgitation was still significant after 1 month: cisapride from 6.22 to 1.55 versus domperidone from 4.80 to 1.25. However, the natural decrease in the incidence of regurgitation induced by age should also be considered. The median reflux index decreased after 1 month in the cisapride group from 3.60 to 1.75 versus from 2.70 to 2.45 in the domperidone group. One child treated with cisapride developed a significant QT prolongation.
Conclusion: The decrease in regurgitation was comparable in both groups, although acid reflux decreased more in the cisapride group. Cisapride induced QT prolongation in one infant.     

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.