ECTOPIC trial: The efficacy of flEcainide Compared To metOprolol in reducing Premature ventrIcular Contractions: A randomized open-label crossover study in pediatric patients.

BACKGROUND: Frequent premature ventricular contractions (PVCs) in children are usually considered benign. Symptoms and left ventricular dysfunction are indications for treatment with antiarrhythmic drugs. OBJECTIVE: This study aimed to evaluate the efficacy of flecainide vs metoprolol in reducing PVCs in children. METHODS: A randomized open-label crossover trial was conducted of children with a PVC burden of >15% on Holter monitoring successively treated with metoprolol and flecainide, or vice versa, with a drug-free interval of at least 2 weeks. Holter measurements were repeated before and after the start of the antiarrhythmic drug. RESULTS: Sixty patients were screened; 19 patients could be included. Median age was 13.9 years (interquartile range, 5.5 years). Mean baseline PVC burden was 21.7% (n = 18; SD ± 14.0) before the start of flecainide and 21.2% (n = 17; SD ± 11.5) before the start of metoprolol. In a mixed model analysis, the estimated mean reduction in PVC burden was 10.6 percentage points (95% CI, 5.8-15.3) for flecainide and 2.4 percentage points (95% CI,2.7-7.5) for metoprolol, with a significant difference of 8.2 percentage points (95% CI, 0.86-15.46; P = .031). Exploratory analysis revealed that 9 of 18 patients treated with flecainide and 1 of 17 patients treated with metoprolol had a reduction to a PVC burden below 5%. No discriminating factors between flecainide responders and nonresponders were found; the mean plasma level was not significantly different (0.34 mg/L vs 0.52 mg/L; P = .277). CONCLUSION: In children with frequent PVCs, flecainide led to a significantly greater reduction of PVC burden compared with metoprolol. Flecainide was effective in only a subgroup of patients, which appears to be unrelated to the plasma level.

The effect of electro-anatomical mapping on the success rate and fluoroscopy time in supra-ventricular tachycardia ablation in children: single centre retrospective study.

AIMS: To evaluate the effect of electro-anatomical mapping on success rate and fluoroscopy time in ablation of supraventricular tachycardia substrates in a large group of children. METHODS: Patients referred from multiple centres in the Netherlands and who received a first ablation for supraventricular tachycardia substrates in the Leiden University Medical Center between 2014 and 2020 were included in this retrospective cohort study. They were divided in procedures in patients with fluoroscopy and procedures in patients using electro-anatomical mapping. RESULTS: Outcomes of ablation of 373 electro-anatomical substrates were analysed. Acute success rate in the fluoro-group (n = 170) was 95.9% compared to 94.5% in the electro-anatomical mapping group (n = 181) (p = 0.539); recurrence rate was 6.1% in the fluoro-group and 6.4% in the electro-anatomical mapping group (p = 0.911) after a 12-months follow-up. Redo-ablations were performed in 12 cases in the fluoro-group and 10 cases in the electro-anatomical mapping group, with a success rate of 83.3% versus 80.0%, resulting in an overall success rate of 95.9% in the fluoro-group and 92.8% in the electro-anatomical mapping group (p = 0.216) after 12 months. Fluoroscopy time and dose area product decreased significantly from 16.00 ± 17.75 minutes (median ± interquartile range) to 2.00 ± 3.00 minutes (p = 0.000) and 210.5 µGym2 ± 249.3 to 32.9 µGym2 ± 78.6 (p = 0.000), respectively. In the fluoro-group, four complications occurred (2.0%) and in the electro-anatomical mapping group no complications occurred. CONCLUSION: These results demonstrate that ablations of supraventricular tachycardia substrates in children remain a highly effective and safe treatment after the introduction of electro-anatomical mapping as a standard of care, while significantly reducing fluoroscopy time and dose area product.

Objective Home-Monitoring of Physical Activity, Cardiovascular Parameters, and Sleep in Pediatric Obesity.

Introduction: Clinical research and treatment of childhood obesity is challenging, and objective biomarkers obtained in a home-setting are needed. The aim of this study was to determine the potential of novel digital endpoints gathered by a home-monitoring platform in pediatric obesity. Methods: In this prospective observational study, 28 children with obesity aged 6-16 years were included and monitored for 28 days. Patients wore a smartwatch, which measured physical activity (PA), heart rate (HR), and sleep. Furthermore, daily blood pressure (BP) measurements were performed. Data from 128 healthy children were utilized for comparison. Differences between patients and controls were assessed via linear mixed effect models. Results: Data from 28 patients (average age 11.6 years, 46% male, average body mass index 30.9) and 128 controls (average age 11.1 years, 46% male, average body mass index 18.0) were analyzed. Patients were recruited between November 2018 and February 2020. For patients, the median compliance for the measurements ranged from 55% to 100% and the highest median compliance was observed for the smartwatch-related measurements (81-100%). Patients had a lower daily PA level (4,597 steps vs. 6,081 steps, 95% confidence interval [CI] 862-2,108) and peak PA level (1,115 steps vs. 1,392 steps, 95% CI 136-417), a higher nighttime HR (81 bpm vs. 71 bpm, 95% CI 6.3-12.3) and daytime HR (98 bpm vs. 88 bpm, 95% CI 7.6-12.6), a higher systolic BP (115 mm Hg vs. 104 mm Hg, 95% CI 8.1-14.5) and diastolic BP (76 mm Hg vs. 65 mm Hg, 95% CI 8.7-12.7), and a shorter sleep duration (difference 0.5 h, 95% CI 0.2-0.7) compared to controls. Conclusion: Remote monitoring via wearables in pediatric obesity has the potential to objectively measure the disease burden in the home-setting. The novel endpoints demonstrate significant differences in PA level, HR, BP, and sleep duration between patients and controls. Future studies are needed to determine the capacity of the novel digital endpoints to detect effect of interventions.

[Multisystem inflammatory syndrome associated with COVID-19: Not just a pediatric disease]. / Covid-19-geassocieerde 'multisystem inflammatory syndrome'.

BACKGROUND: Since the start of the COVID-19 pandemic, a hyperinflammatory syndrome has appeared which develops weeks after a SARS-CoV-2 infection. This multisystem inflammatory syndrome has been described mainly in children (MIS-C), but lately has also been found in adults (MIS-A). CASE DESCRIPTION: We present a case of a woman with MIS-A. She had fever, diarrhoea, hypotension, laboratory abnormalities with high inflammatory markers, coagulation parameters, troponin-T, N-terminal pro-brain natriuretic peptide (NT-proBNP). Her electrocardiogram had marked diffuse ST-depressions. She was diagnosed in an early stage of MIS-A and treated successfully with immune suppression, antiaggregants and anticoagulants. CONCLUSION: MIS-A and MIS-C are similar, potentially life-threatening inflammatory syndromes which can lead to severe cardiac dysfunction and cardiovascular failure. For effective treatment and prevention of complications, timely recognition is essential. Clinicians should therefore be mindful of this multisystem inflammatory syndrome, not just in children but also in adults.

Diagnostic accuracy of the response to the brief tachycardia provoked by standing in children suspected for long QT syndrome.

BACKGROUND: Adult long QT syndrome (LQTS) patients have inadequate corrected QT interval (QTc) shortening and an abnormal T-wave response to the sudden heart rate acceleration provoked by standing. In adults, this knowledge can be used to aid an LQTS diagnosis and, possibly, for risk stratification. However, data on the diagnostic value of the standing test in children are currently limited. OBJECTIVE: To determine the potential value of the standing test to aid LQTS diagnostics in children. METHODS: In a prospective cohort including children (≤18 years) who had a standing test, comprehensive analyses were performed including manual and automated QT interval assessments and determination of T-wave morphology changes. RESULTS: We included 47 LQTS children and 86 control children. At baseline, the QTc that identified LQTS children with a 90% sensitivity was 435 ms, which yielded a 65% specificity. A QTc ≥ 490 ms after standing only slightly increased sensitivity (91%, 95% confidence interval [CI]: 80%-98%) and slightly decreased specificity (58%, 95% CI: 47%-70%). Sensitivity increased slightly more when T-wave abnormalities were present (94%, 95% CI: 82%-99%; specificity 53%, 95% CI: 42%-65%). When a baseline QTc ≥ 440 ms was accompanied by a QTc ≥ 490 ms and T-wave abnormalities after standing, sensitivity further increased (96%, 95% CI: 85%-99%) at the expense of a further specificity decrease (41%, 95% CI: 30%-52%). Beat-to-beat analysis showed that 30 seconds after standing, LQTS children had a greater increase in heart rate compared to controls, which was more evidently present in LQTS boys and LQTS type 1 children. CONCLUSION: In children, the standing test has limited additive diagnostic value for LQTS over a baseline electrocardiogram, while T-wave abnormalities after standing also have limited additional value. The standing test for LQTS should only be used with caution in children.

The Efficacy of Anti-Arrhythmic Drugs in Children With Idiopathic Frequent Symptomatic or Asymptomatic Premature Ventricular Complexes With or Without Asymptomatic Ventricular Tachycardia: a Retrospective Multi-Center Study.

The aim of the study is to compare the efficacy of flecainide, beta-blockers, sotalol, and verapamil in children with frequent PVCs, with or without asymptomatic VT. Frequent premature ventricular complexes (PVCs) and asymptomatic ventricular tachycardia (VT) in children with structurally normal hearts require anti-arrhythmic drug (AAD) therapy depending on the severity of symptoms or ventricular dysfunction; however, data on efficacy in children are scarce. Both symptomatic and asymptomatic children (≥ 1 year and < 18 years of age) with a PVC burden of 5% or more, with or without asymptomatic runs of VT, who had consecutive Holter recordings, were included in this retrospective multi-center study. The groups of patients receiving AAD therapy were compared to an untreated control group. A medication episode was defined as a timeframe in which the highest dosage at a fixed level of a single drug was used in a patient. A total of 35 children and 46 medication episodes were included, with an overall change in PVC burden on Holter of -4.4 percentage points, compared to -4.2 in the control group of 14 patients. The mean reduction in PVC burden was only significant in patients receiving flecainide (- 13.8 percentage points; N = 10; p = 0.032), compared to the control group and other groups receiving beta-blockers (- 1.7 percentage points; N = 18), sotalol (+ 1.0 percentage points; N = 7), or verapamil (- 3.9 percentage points; N = 11). The efficacy of anti-arrhythmic drug therapy on frequent PVCs or asymptomatic VTs in children is very limited. Only flecainide appears to be effective in lowering the PVC burden.

[COVID-19-associated hyperinflammatory state in a 15-year-old female patient]. / Covid-19-geassocieerde hyperinflammatie.

Paediatric Multisystem Inflammatory Syndrome Temporally Related to SARS-CoV-2 (PIMS-TS) is a rare novel clinical entity observed in children and adolescents with evidence of a recent COVID-19 infection, and is characterized by a marked hyperinflammatory state with involvement of multiple organ systems.We report a case of a previously healthy 15-year-old female patient, who was admitted to paediatric intensive care with cardiac failure and was subsequently shown to have positive COVID-19 serology. The presenting symptoms were fever, cough, chest pain and gastro-intestinal symptoms. She was supported with milrinone and a low dose of vasopressors. Her hyperinflammatory state was treated with intravenous immunoglobulins, high dose aspirin and high-dose methylprednisolone. PIMS-TS is a rare, potentially life threatening novel clinical entity in children and adolescents with evidence of a COVID-19 infection. Clinicians need to be aware of the possibility of this new disease, to ensure prompt recognition and treatment.

Risk of Clinically Relevant Pericardial Effusion After Pediatric Cardiac Surgery.

Pericardial effusion (PE) after pediatric cardiac surgery is common. Because of the lack of a uniform classification of the presence and severity of PE, we evaluated PE altering clinical management: clinically relevant PE. Risk factors for clinically relevant PE were studied. After cardiac surgery, children were followed until 1 month after surgery. Preoperative variables were studied in the complete cohort. Perioperative and postoperative variables were studied in a case-control manner. Patients with and without clinically relevant PE were matched on age, gender, and diagnosis severity in a 1:1 ratio. Multivariate analysis was conducted using important preoperative variables from the complete cohort combined with perioperative and postoperative variables from the case-control data. 1241 surgical episodes in 1031 patients were included. Clinically relevant PE developed in 136 episodes (11.0%). Multivariate correlation with the outcome was present for age, BSA (adjusted odds ratio: 1.6, 95% CI 0.9-2.8), right-sided heart defect (adjusted odds ratio: 1.3, 95% CI 0.9-1.9), history of previous operation (adjusted odds ratio: 0.5, 95% CI 0.3-0.7), cardiopulmonary bypass use (adjusted odds ratio: 2.1, 95% CI 0.9-4.5), duration of CPAP postoperatively, and an inotropic score (adjusted odds ratio: 1.01, 95% CI 0.998-1.03). In this large patient cohort, 11.0% of postoperative periods of pediatric cardiac surgery were complicated by PE requiring alteration of treatment. Secondly, we newly identified cardiopulmonary bypass use and right-sided heart defects as risk factors for clinically relevant PE and confirmed previously described risk factors: age, CPAP duration, BSA, and inotropic score and a previously described risk reductor: history of previous operation.

The development and validation of an easy to use automatic QT-interval algorithm.

BACKGROUND: To evaluate QT-interval dynamics in patients and in drug safety analysis, beat-to-beat QT-interval measurements are increasingly used. However, interobserver differences, aberrant T-wave morphologies and changes in heart axis might hamper accurate QT-interval measurements. OBJECTIVE: To develop and validate a QT-interval algorithm robust to heart axis orientation and T-wave morphology that can be applied on a beat-to-beat basis. METHODS: Additionally to standard ECG leads, the root mean square (ECGRMS), standard deviation and vectorcardiogram were used. QRS-onset was defined from the ECGRMS. T-wave end was defined per individual lead and scalar ECG using an automated tangent method. A median of all T-wave ends was used as the general T-wave end per beat. Supine-standing tests of 73 patients with Long-QT syndrome (LQTS) and 54 controls were used because they have wide ranges of RR and QT-intervals as well as changes in T-wave morphology and heart axis orientation. For each subject, automatically estimated QT-intervals in three random complexes chosen from the low, middle and high RR range, were compared with manually measured QT-intervals by three observers. RESULTS: After visual inspection of the randomly selected complexes, 21 complexes were excluded because of evident noise, too flat T-waves or premature ventricular beats. Bland-Altman analyses of automatically and manually determined QT-intervals showed a bias of <4ms and limits of agreement of ±25ms. Intra-class coefficient indicated excellent agreement (>0.9) between the algorithm and all observers individually as well as between the algorithm and the mean QT-interval of the observers. CONCLUSION: Our automated algorithm provides reliable beat-to-beat QT-interval assessment, robust to heart axis and T-wave morphology.

Tissue Doppler imaging in the left ventricle and right ventricle in healthy children: normal age-related peak systolic velocities, timings, and time differences.

AIMS: Tissue Doppler imaging (TDI) enables assessment of velocities and timings within the left (LV) and the right (RV) ventricle with high temporal resolution. Knowledge on normal age-related values of peak systolic velocities and timings in healthy children may optimize the benefit of device-based therapies in paediatric patients with heart failure. METHODS AND RESULTS: A total of 123 healthy children (from 1 month to 18 years old) underwent TDI evaluation of the RV and LV. Peak systolic velocity and time to peak systolic velocity were assessed at the basal LV lateral wall, inter-ventricular septum (IVS), RV free wall (RVFW), and at the RV outflow tract (RVOT). Intra-ventricular time differences were calculated. Regression analysis was performed to assess the age dependency of the ventricular mechanics. Median peak velocities were: LV lateral wall: 6.3 cm/s (inter-quartile range (IQR): 5.1-7.9 cm/s); IVS: 6.0 cm/s (5.4-6.7 cm/s); RVFW: 10.2 cm/s (8.9-11.3 cm/s); RVOT: 7.2 cm/s (6.0-8.2 cm/s). Timings of peak systolic velocities were: LV lateral wall: 101 ms (91-112 ms); IVS: 114 ms (100-128 ms); RVFW: 177 ms (157-194 ms); RVOT: 100 ms (88-113 ms). Timings and peak velocities significantly increased with age at both ventricles. No relevant time difference was observed within the LV, whereas a considerable time delay was observed within the RV between the RVFW and the IVS (62 ms, IQR: 45-74 ms) and between the RVFW and the RVOT (74 ms, IQR: 59-93 ms). CONCLUSION: The present evaluation provides TDI-derived physiological values on normal LV and RV mechanics of healthy children. Within the LV, no relevant time difference was observed, whereas a considerable mechanical delay is observed within the healthy RV.

The role of the epinephrine test in the diagnosis and management of children suspected of having congenital long QT syndrome.

The epinephrine test has been shown to be a powerful tool to predict the genotype of congenital long QT syndrome (LQTS). The aim of this study was to evaluate its role in the diagnosis and management of LQTS in children. The test (using the Shimizu protocol) was conducted in patients with some evidence of LQTS but in whom clinical and management decisions were challenging (n = 41, age 9.6 +/- 3.9 years, 19 female). LQT1, LQT2, and negative responses to epinephrine were obtained in 16, 5, and 20 subjects, respectively. LQTS gene positivity was obtained in two subjects. Beta-blocker therapy was started in all subjects with a positive epinephrine response (n = 21) and in some negative responders because of their strong LQTS phenotype (n = 10). No therapy was given to the subset with less convincing features of LQTS who had also responded negatively to epinephrine (n = 10). Follow-up for 3.0 +/- 2 years was uneventful in both management groups. Due to the discordance with genotyping, the epinephrine test cannot be used to diagnose genotype-positive LQTS but when used in combination with phenotype assessment and genetic screening, it could enable better management decisions.

Simultaneous repair of supravalvar aortic and supravalvar pulmonary stenosis using the 3-patch technique.

Patients with Williams-Beuren syndrome may have bilateral outflow tract obstruction. We report a simultaneous repair of supravalvar aortic and supravalvar pulmonary stenosis using the 3-patch technique.

Early atrial septal defect surgery due to a bronchogenic cyst causing congestive heart failure by left atrium compression.

We report on an uncommon case of a 10-month-old patient who required early surgical closure of an ostium secumdum atrial septal defect due to the concomitant presence of a big subcarinal bronchogenic cyst compressing the left atrium and, therefore, increasing the left-to-right shunt. It led to refractory congestive heart failure symptoms, establishing thereby an earlier indication of surgical treatment.