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Background: Patients with repaired tetralogy of Fallot (rTOF) have a time-dependent increased risk of ventricular tachycardia (VT). Slow conducting anatomical isthmuses (SCAIs) are the dominant VT substrates in adults with rTOF. It is unknown if they are present at younger age., Objectives: This study aimed to characterize VT substrates in patients with rTOF <30 years of age., Methods: Data of consecutive patients with rTOF aged <30 years who underwent electroanatomical mapping and programmed electrical stimulation between 2005 and 2022 were analyzed., Results: Fifty-five patients were included (median age: 15.8 years, IQR: 13.8-21.8 years; 15 repaired via ventriculotomy; 13 complex TOF variants). Twelve patients had right ventricle-to-pulmonary artery conduits inserted during initial repair or had early pulmonary valve replacement (PVR) (<1 year after repair). Indications for electroanatomical mapping and programmed electrical stimulation were spontaneous VT, before PVR, and risk stratification in 5, 40, and 10 patients, respectively. In 16 patients (29%), SCAI 3 was identified; no other SCAI was present. Monomorphic VT was inducible in 8 and related to SCAI 3 in 7 patients. Identified VT substrates were targeted by ablation. Right ventricle-to-pulmonary artery conduit/early PVR, ventriculotomy, and complex TOF were associated with SCAI 3 in univariable analysis. During a median follow-up of 5.3 years, VT recurred in 2 patients. No patients died., Conclusions: In young patients with rTOF, SCAI 3 is the dominant substrate for VT. Complex TOF and interrelated type and timing of (re-)operation may contribute to the development of SCAI 3 already at a young age., Competing Interests: Funding Support and Author Disclosures The authors acknowledge the support from the Netherlands Cardiovascular Research initiative: An initiative with support of the Dutch Heart Foundation and Hartekind, CVON2019-002 OUTREACH. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

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 µGym 2 ± 249.3 to 32.9 µGym 2 ± 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.

Background: Balloon atrial septostomy (BAS) is an emergent and essential cardiac intervention to enhance intercirculatory mixing at atrial level in deoxygenated patients diagnosed with transposition of the great arteries (TGA) and restrictive foramen ovale. The recent recall of several BAS catheters and the changes in the European legal framework for medical devices (MDR 2017/745), has led to an overall scarcity of BAS catheters and raised questions about the use, safety, and experience of the remaining NuMED Z-5 BAS catheter., Aims: To evaluate and describe the practice and safety of the Z-5 BAS catheter, and to compare it to the performance of other BAS catheters., Methods: A retrospective single-center cohort encompassing all BAS procedures performed with the Z-5 BAS catheter in TGA patients between 1999 and 2022., Results: A total of 182 BAS procedures were performed in 179 TGA-newborns at Day 1 (IQR 0-5) days after birth, with median weight of 3.4 (IQR 1.2-5.7) kg. The need for BAS was urgent in 90% of patients. The percentage of BAS procedures performed at bedside increased over time from 9.8% (before 2010) to 67% (2017-2022). Major complication rate was 2.2%, consisting of cerebral infarction (1.6%) and hypovolemic shock (0.5%). The rate of minor complications was 9.3%, including temporary periprocedural AV-block (3.8%), femoral vein thrombosis (2.7%), transient intracardiac thrombus (0.5%), and atrial flutter (2.2%). BAS procedures performed at bedside and in the cardiac catheterization laboratory had similar complication rates., Conclusions: BAS using the Z-5 BAS catheter is both feasible and safe at bedside and at the cardiac catheterization laboratory with minimal major complications., (© 2023 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Background: Variants in KCNH2, encoding the human ether a-go-go (hERG) channel that is responsible for the rapid component of the cardiac delayed rectifier K+ current (IKr), are causal to long QT syndrome type 2 (LQTS2). We identified eight index patients with a new variant of unknown significance (VUS), KCNH2:c.2717C > T:p.(Ser906Leu). We aimed to elucidate the biophysiological effect of this variant, to enable reclassification and consequent clinical decision-making., Methods: A genotype-phenotype overview of the patients and relatives was created. The biophysiological effects were assessed independently by manual-, and automated calibrated patch clamp. HEK293a cells expressing (i) wild-type (WT) KCNH2, (ii) KCNH2-p.S906L alone (homozygous, Hm) or (iii) KCNH2-p.S906L in combination with WT (1:1) (heterozygous, Hz) were used for manual patching. Automated patch clamp measured the variants function against known benign and pathogenic variants, using Flp-In T-rex HEK293 KCNH2-variant cell lines., Results: Incomplete penetrance of LQTS2 in KCNH2:p.(Ser906Leu) carriers was observed. In addition, some patients were heterozygous for other VUSs in CACNA1C, PKP2, RYR2 or AKAP9. The phenotype of carriers of KCNH2:p.(Ser906Leu) ranged from asymptomatic to life-threatening arrhythmic events. Manual patch clamp showed a reduced current density by 69.8 and 60.4% in KCNH2-p.S906L-Hm and KCNH2-p.S906L-Hz, respectively. The time constant of activation was significantly increased with 80.1% in KCNH2-p.S906L-Hm compared with KCNH2-WT. Assessment of KCNH2-p.S906L-Hz by calibrated automatic patch clamp assay showed a reduction in current density by 35.6%., Conclusion: The reduced current density in the KCNH2-p.S906L-Hz indicates a moderate loss-of-function. Combined with the reduced penetrance and variable phenotype, we conclude that KCNH2:p.(Ser906Leu) is a low penetrant likely pathogenic variant for LQTS2., (© The Author(s) 2022. Published by Oxford University Press.)

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.

Background: In response to an increased need for patient information in congenital heart disease, we previously developed an online, evidence-based information portal for patients with congenital aortic and pulmonary valve disease. To assess its effectiveness, a stepped-wedge cluster randomised trial was conducted., Methods: Adult patients and caregivers of paediatric patients with congenital aortic and/or pulmonary valve disease and/or tetralogy of Fallot who visited the outpatient clinic at any of the four participating centres in the Netherlands between 1 March 2016-1 July 2017 were prospectively included. The intervention (information portal) was introduced in the outpatient clinic according to a stepped-wedge randomised design. One month after outpatient clinic visit, each participant completed a questionnaire on disease-specific knowledge, anxiety, depression, mental quality of life, involvement and opinion/attitude concerning patient information and involvement., Results: 343 participants were included (221 control, 122 intervention). Cardiac diagnosis (p=0.873), educational level (p=0.153) and sex (p=0.603) were comparable between the two groups. All outcomes were comparable between groups in the intention-to-treat analyses. However, only 51.6% of subjects in the intervention group (n=63) reported actually visiting the portal. Among these subjects (as-treated), disease-specific knowledge (p=0.041) and mental health (p=0.039) were significantly better than in control subjects, while other baseline and outcome variables were comparable., Conclusion: Even after being invited by their cardiologists, only half of the participants actually visited the information portal. Only in those participants that actually visited the portal, knowledge of disease and mental health were significantly better. This underlines the importance of effective implementation of online evidence-based patient information portals in clinical practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: In response to an increased need for patient information on congenital heart disease in the Netherlands, we initiated a nationwide initiative to develop an online, evidence-based patient information portal, starting with a pilot project aimed at the subgroup of patients with congenital aortic and pulmonary valve disease., Methods and Results: We developed an information portal that aims to (1) improve patient knowledge and involvement and to subsequently reduce anxiety and decisional conflict and improve mental quality of life and (2) to support physicians in informing and communicating with their patients. The information portal was developed according to the systematic International Patient Decision Aid Standards development process employing Delphi techniques by a multidisciplinary workgroup of pediatric and adult congenital cardiologists, a congenital cardiothoracic surgeon, a psychologist, an epidemiologist, a patient representative, and web and industrial design experts. First, patients and physicians were surveyed and interviewed to assess the current state of patient information and explore their preferences and needs to determine the focus for the development of the information portal. We found that patient knowledge and numeracy are limited, reliable information is scarce, physicians inform patients selectively and patient involvement is suboptimal, and there is a need for more reliable, tailored, and multi-faceted information. Based on the findings of these surveys and interviews, a patient-tailored information portal was designed that presents evidence-based disease- and age-specific medical and psychosocial information about diagnosis, treatment, prognosis, and impact on daily life in a manner that is comprehensible and digestible for patients and that meets the needs expressed by both patients and physicians. The effect of the website on patient outcome is currently being assessed in a multicenter stepped-wedge implementation trial., Conclusion: The present pilot project succeeded in developing an online, evidence-based information portal that is supported by both patients and physicians. The information portal will be further developed and expanded to include all other major forms of congenital heart disease, translations into other languages, and a public information portal to serve patients' relatives and the general public at large.

Aims: To assess the risk factors for left ventricular (LV) dysfunction in a paediatric population with idiopathic frequent premature ventricular contractions (PVCs) and asymptomatic ventricular tachycardias (VTs)., Methods and Results: Paediatric patients with the diagnosis of idiopathic frequent PVCs and asymptomatic VTs were retrospectively evaluated. Frequent PVCs were defined as ≥5% on 24 h Holter recording. Left ventricular dysfunction was defined as a shortening fraction of ≤28%. Seventy-two children were identified. Six patients showed LV dysfunction at diagnosis [age 10 ± 7 years, 2 (33%) had symptoms such as syncope, palpitations, fatigue, and dizziness], and 66 showed normal LV function [age 8 ± 6 years, 22 (33%) with symptoms]. Patients with LV dysfunction had a higher percentage of PVCs on Holter recordings (47 ± 16 vs. 16 ± 11%, P = 0.006), higher prevalence of VT [5 (83%) vs. 27 (41%), P = 0.045] and sustained ventricular tachycardia (sVT) [3 (50%) vs. 4 (6%), P = 0.001], and a higher number of couplets [6 (100%) vs. 34 (52%), P = 0.030]. In patients with LV dysfunction, two responded to medication (Classes Ic and II) and five underwent ablation, of which one was unsuccessful. During follow-up, LV function normalized in five of six patients. In patients with a normal function, none developed LV dysfunction during the follow-up., Conclusion: In children with idiopathic PVCs and asymptomatic VTs, development of LV dysfunction is associated with a higher burden of PVCs, the presence of sVTs, and couplets. Left ventricular dysfunction appears to be reversible if the burden of PVCs is decreased by medication or ablation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Objectives: To evaluate the results of balloon dilatation of stenotic homografts in children, adolescents, and young adults and to identify factors that might influence or predict the effect of the dilatation., Background: Homografts are widely used in congenital cardiac surgery; however, the longevity remains a problem mostly because of stenosis in the homograft. The effect of treatment by balloon dilatation is unclear., Methods: In a retrospective study, the effect of balloon dilatation was determined by the percentage of reduction of the peak systolic pressure gradient over the homograft during catheterisation and the postponement of re-intervention or replacement of the homograft in months. Successful dilatations - defined in this study as a reduction of more than 33% and postponement of more than 18 months - were compared with unsuccessful dilatations in search of factors influencing or predicting the results., Results: The mean reduction of the peak systolic pressure gradient was 30% in 40 procedures. Re-intervention or replacement of the homograft was postponed by a mean of 19 months. In all, 14 balloon dilatations (35%) were successful; the mean reduction was 49% and the mean postponement was 34 months. The time since homograft implantation, the presence of calcification, the homograft/balloon ratio, and the pressure applied during dilatation all tended to correlate with outcome, but were not statistically significant., Conclusions: Balloon dilatation is able to reduce the peak systolic pressure gradient over homografts in a subgroup of patients and can be of clinical significance to postpone re-intervention or pulmonary valve replacement.

Introduction: Continuous infusion of cefotaxime, as opposed to intermittent infusion, seems to be advantageous for a number of reasons. However, few data exist on pharmacokinetics of cefotaxime and its metabolite in infants and children. As part of a quality assessment program, concentrations of cefotaxime and its metabolite desacetyl-cefotaxime were examined., Methods: Infants and children (age 0-17 years) routinely received cefotaxime by continuous intravenous infusion and had blood samples taken on days 1, 3, and 5 after start of therapy. Measurements were performed by high-performance liquid chromatography (HPLC) of cefotaxime and desacetyl-cefotaxime., Results: Patients receiving a dosage of 100 mg/kg/day had a mean cefotaxime concentration of 24.9 mg/l on day 1, ranging from 0.6 to 182.6 mg/l (N = 222). Cefotaxime concentrations in infants younger than 1 week of age showed the largest variation and significantly decreased on consecutive days (p < 0.001, N = 17), together with a significant drop in the cefotaxime-desacetyl-cefotaxime (cef-des) ratio (p = 0.003, N = 16). Cefotaxime clearance increased significantly during the first days after birth (p = 0.024, N = 16). Patients older than 1 week showed negative and significant correlations of cefotaxime concentrations with calculated glomerular filtration rates (p < 0.0001, N = 73), with no significant change in the cef- des ratio on consecutive days., Conclusion: Overall, cefotaxime concentrations varied widely between patients, in particular in those younger than 1 week. Our data suggest that liver metabolism as well as renal excretion contribute to total body clearance of cefotaxime and increase during the first few days of live.

Objective: To assess the number of possible candidates for paediatric cardiac transplantation and the number of available donors., Design: Retrospective., Patients and Methods: The population (date of birth 1 January 1980-31 March 1998) of the Department of Paediatric Cardiology of the Wilhelmina Children's Hospital, Utrecht, the Netherlands, was reviewed for possible candidates for cardiac transplantation and the resulting number of candidates was extrapolated to the entire country. Figures of the transplant co-ordination unit of the University Hospital Utrecht over 1993-1997 were obtained, to estimate the number of available donors. Furthermore, an overview was made of the results of paediatric cardiac transplantations reported in centres around the world., Results: A total number of 15 possible candidates could be selected over the studied period. Extrapolated to the entire country, about 5 candidates each year could be expected. Per year 5 donor hearts of children (< 12 yr) and 11 hearts of adult donors with a low body weight (40-65 kg) have been available for paediatric cardiac transplantation. Worldwide 5- and 10-year survival rates reach 60% and 50%, respectively, morbidity seems low and the quality of life can be considered reasonably good., Conclusion: The number of expected recipients corresponds with the number of available donors. Together with the promising results reported in transplant centres around the world, this seems to justify the option of paediatric cardiac transplantation for children with end-stage cardiac disease.