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:... Show moreAims: 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 mu Gym(2) +/- 249.3 to 32.9 mu Gym(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 supra-ventricular 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. Show less
Monteros, C.T.E. de los; Palen, R.L.F. van der; Nederend, I.; Geus, E.J.C. de; Kuipers, I.M.; Hazekamp, M.G.; ... ; Harkel, A.D.J. ten 2022
BackgroundA chronic imbalance of the autonomic nervous system(ANS) may contribute to long term complications in different congenital heart diseases. The purpose of this study was to determine... Show moreBackgroundA chronic imbalance of the autonomic nervous system(ANS) may contribute to long term complications in different congenital heart diseases. The purpose of this study was to determine whether the ASN plays a role in the long-term outcome of patients with Transposition of great arteries(TGA) after arterial switch operation(ASO) as its contribution is as yet not clear.MethodsThe ANS activity was evaluated non-invasively in 26 TGA patients and 52 age-appropriate healthy subjects combining impedance cardiography and electrocardiography. Heart rate, pre-ejection period(sympathetic activity parameter) and respiratory sinus arrhythmia and the root of the mean square of successive normal-to-normal interval differences(parasympathetic activity parameter) were measured during 5 different daily activities(sleep, sitting, active sitting, light and moderate/vigorous physical activity). Whether the ANS activity was related to ventricular function, exercise test performance or clinical outcome in the patient group was also analyzed.ResultsCompared to healthy subjects: heart rate was significantly lower in TGA patients at rest and during quiet and active sitting; sympathetic activity was significantly reduced in patients during physical activity; and the parasympathetic activity was higher in TGA patients while quiet and active sitting. In the patient group a significant positive correlation between 4-chamber longitudinal strain and parasympathetic activity during 3 different daily activities was found.ConclusionsThe sympathetic nervous system response to physical activity is reduced in TGA patients after ASO. Additionally, we observed a positive correlation between better left ventricular function and higher parasympathetic activity that could be in line with the known protective effect of a higher vagal activity. Show less
Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe inflammatory disease in children related to SARS-CoV-2 with multisystem involvement including marked cardiac dysfunction and... Show moreMultisystem Inflammatory Syndrome in Children (MIS-C) is a severe inflammatory disease in children related to SARS-CoV-2 with multisystem involvement including marked cardiac dysfunction and clinical symptoms that can resemble Kawasaki Disease (KD). We hypothesized that MIS-C and KD might have commonalities as well as unique inflammatory responses and studied these responses in both diseases. In total, fourteen children with MIS-C (n=8) and KD (n=6) were included in the period of March-June 2020. Clinical and routine blood parameters, cardiac follow-up, SARS-CoV-2-specific antibodies and CD4+ T-cell responses, and cytokine-profiles were determined in both groups. In contrast to KD patients, all MIS-C patients had positive Spike protein-specific CD3(+) CD4(+) T-cell responses. MIS-C and KD patients displayed marked hyper-inflammation with high expression of serum cytokines, including the drug-targetable interleukin (IL)-6 and IFN-gamma associated chemokines CXCL9, 10 and 11, which decreased at follow-up. No statistical differences were observed between groups. Clinical outcomes were all favourable without cardiac sequelae at 6 months follow-up. In conclusion, MIS-C and KD-patients both displayed cytokine-associated hyper-inflammation with several high levels of drug-targetable cytokines. Show less
In patients with congenital heart disease (CHD), reduced exercise capacity can be a predictor for late complications and may be used to guide interventions. Yet, the interpretation of exercise... Show moreIn patients with congenital heart disease (CHD), reduced exercise capacity can be a predictor for late complications and may be used to guide interventions. Yet, the interpretation of exercise capacity is challenged by changes in body composition during growth. Our aim was to create an overview of disease-specific exercise capacity in children with CHD. We performed a multicentre retrospective study of exercise capacity of CHD patients, aged 6-18 years, tested between January 2001 and October 2018. Sex-specific distribution graphs were made using the LMS method and height to relate to body size. We included all CHD with N > 50, including severe defects (e.g., univentricular heart, tetralogy of Fallot) and "simple" lesions as ventricular septum defect and atrial septum defect. We included 1383 tests of 1208 individual patients for analysis. The peak oxygen uptake (VO(2)peak, 37.3 ml/min/kg (25th-75th percentile 31.3-43.8)) varied between specific defects; patients with univentricular hearts had lower VO2peak compared with other CHD. All groups had lower VO2peak compared to healthy Dutch children. Males had higher VO2peak, W-peak and O(2)pulse(peak) than females. Sex- and disease-specific distribution graphs for VO2peak, W-peak and O2pulse(peak) showed increase in variation with increase in height.Conclusion: Disease-specific distribution graphs for exercise capacity in children with CHD from a large multicentre cohort demonstrated varying degrees of reduced VO2peak and W-peak. The distribution graphs can be used in the structured follow-up of patients with CHD to predict outcome and identify patients at risk. Show less
Background: Many cardiocirculatory mechanisms are involved in the adaptation to orthostatic stress. While these mechanisms may be impaired in Fontan patients. However, it is yet unclear how Fontan... Show moreBackground: Many cardiocirculatory mechanisms are involved in the adaptation to orthostatic stress. While these mechanisms may be impaired in Fontan patients. However, it is yet unclear how Fontan patients, who exhibit a critical fluid balance, respond to orthostatic stress. Angiotensin converting enzyme inhibitors are often prescribed to Fontan patients, but they may negatively influence orthostatic tolerance. Therefore, we evaluated the response to orthostatic stress in pediatric Fontan patients before and after treatment with enalapril. Methods: Thirty-five Fontan patients (aged 14 years) with moderate-good systolic ventricular function without pre-existent enalapril treatment were included. Before and after a three-month enalapril treatment period, the hemodynamic response to head-up tilt test was evaluated by various parameters including cardiac index, blood pressure, cerebral blood flow, aortic stiffness and cardiac autonomous nervous activity. Thirty-four healthy subjects (aged 13 years) served as controls. Results: Fontan patients had a decreased cerebral blood flow and increased aortic stiffness in the supine position compared to controls, while all other factors did not differ. Patients and controls showed a comparable response to head-up tilt test for most parameters. Twenty-seven patients completed the enalapril study with a mean dosage of 0.3 +/- 0.1mg/kg/day. Most parameters were unaffected by enalapril, only the percent decrease in cardiac index to tilt was higher after treatment, but the cardiac index during tilt was not lower (3.0L/min/m(2) preenalapril versus 2.8L/min/m(2) after treatment; P = 0.15). Conclusion: Pediatric Fontan patients adequately respond to orthostasis with maintenance of blood pressure and cerebral blood flow and sufficient autonomic response. Enalapril treatment did not alter the response. Show less
Harteveld, L.M.; Blom, N.A.; Monteros, C.T.E. de los; Kuipers, I.M.; Rammeloo, L.A.J.; Hazekamp, M.G.; ... ; Harkel, A.D.J. ten 2022
Many Fontan patients with and without systolic ventricular dysfunction are being treated with angiotensin-converting enzyme (ACE) inhibitors, despite its effectiveness remaining unclear. In the... Show moreMany Fontan patients with and without systolic ventricular dysfunction are being treated with angiotensin-converting enzyme (ACE) inhibitors, despite its effectiveness remaining unclear. In the present study, we evaluated the short-term effect of enalapril on exercise capacity, vascular and ventricular function in pediatric Fontan patients with moderategood systolic ventricular function. Fontan patients between 8 and 18 years with moderategood systolic ventricular function and without previous ACE inhibitor treatment were included and were treated with enalapril for 3 months. During the first 2 weeks, the dosage was titrated according to systolic blood pressure (SBP). Exercise tests, ventricular function assessed by echocardiography, arterial stiffness measurements, and plasma levels of N-terminal pro-B-type natriuretic peptide assessed before and after a 3-month enalapril treatment period was compared. A total of 28 Fontan patients (median age 13.9 years, 6 to 15 years after Fontan operation) completed the study with a mean dosage of 0.3 +/- 0.1 mg/ kg/d. A total of 6 patients (21 %) experienced a significant drop in SBP and 6 others (21%) experienced other adverse events. Enalapril treatment lowered the SBP (from 110 to 104 mmHg, p = 0.003) and levels of N-terminal pro-B-type natriuretic peptide (from 80 to 72 ng/L, p = 0.036). However, enalapril treatment did not improve exercise capacity, ventricular function, or arterial stiffness. In conclusion, short-term ACE inhibition has no beneficial effect in Fontan patients with moderate-good systolic ventricular function. (C) 2021 The Authors. Published by Elsevier Inc. Show less
Background: Although various determinants of exercise limitation in Fontan patients have been studied, most research has been performed in patients who underwent different surgical procedures with... Show moreBackground: Although various determinants of exercise limitation in Fontan patients have been studied, most research has been performed in patients who underwent different surgical procedures with differing haemodynamic characteristics. The aim of the current study was to evaluate non-invasively measured cardiovascular parameters and their influence on exercise performance in paediatric Fontan patients with an extracardiac conduit and moderate-good systolic ventricular function. Methods: Fontan patients, between 8 and 18 years of age, with moderate to good systolic ventricular function and an extracardiac conduit were included. Exercise performance and cardiovascular assessment, comprising echocardiography, aortic stiffness measurement and ambulatory measurement of cardiac autonomous nervous activity were performed on the same day. Healthy subjects served as controls. Results: Thirty-six Fontan patients (age 14.0 years) and thirty-five healthy subjects (age 12.8 years) were included. Compared to controls, Fontan patients had reduced diastolic ventricular function and increased arterial stiffness. No differences were found in heart rate (HR) and cardiac parasympathetic nervous activity. In Fontan patients, maximal as well as submaximal exercise capacity was impaired, with the percentage of predicted capacity ranging between 54 and 72%. Chronotropic competence, however, was good with a peak HR of 174 (94% of predicted). Lower maximal and submaximal exercise capacity was correlated with a higher HR at rest, higher pulse wave velocity of the aorta and a lower ratio of early and late diastolic flow velocity. Conclusion: Contemporary paediatric Fontan patients have an impaired exercise capacity with preserved chronotropic competence. Exercise performance correlates with heart rate at rest, diastolic function and aortic stiffness. Show less
Monteros, C.T.E. de los; Harteveld, L.M.; Kuipers, I.M.; Rammeloo, L.; Hazekamp, M.G.; Blom, N.A.; Harkel, A.D.J. ten 2021
Purpose After surgery for congenital heart disease in children and adolescents, an active lifestyle is important to achieve and maintain good physical fitness. This study aimed to describe physical... Show morePurpose After surgery for congenital heart disease in children and adolescents, an active lifestyle is important to achieve and maintain good physical fitness. This study aimed to describe physical activity, as well as the use of patients' and parents' preferences for rehabilitative care after surgery for congenital heart disease. Methods This cross-sectional study included patients aged 4-16 years old, who had undergone surgery for congenital heart disease 2 years prior to the study onset. Patients and/or parents were invited to complete questionnaires on physical activity, and on their preferences for, and -use of, rehabilitative care after surgery. Results Forty-five of the 92 eligible patients and/or parents completed the questionnaires. The median age of the children was 12.2 years (IQR 7.8-16.1). Two children (4%) met the recommendations for taking part in moderate physical activity and 13 (29%) having done so for vigorous physical activity. Postoperatively 15 children (33%) had had physical therapy in primary care. More than 50% of the patients/parents would have preferred to have had more information on physical activity and to have taken part in an individual exercise program delivered during their primary care. Conclusion The majority of eligible patients do not meet public health recommendations for engaging in physical activity and do not use physical therapy after surgery for congenital heart disease. The majority of patients and parents preferred more information as well as individual physical therapy treatments. Show less
OBJECTIVES: The objective of this study was to assess our 43-year experience with arterial switch operation (ASO) for transposition of the great arteries (TGA) by analysing cardiac outcome measures... Show moreOBJECTIVES: The objective of this study was to assess our 43-year experience with arterial switch operation (ASO) for transposition of the great arteries (TGA) by analysing cardiac outcome measures (hospital and late mortality, reoperations and catheter interventions, significant coronary artery obstruction) and to identify risk factors for reoperation and catheter interventions.METHODS: A total of 490 patients who underwent ASO for TGA from 1977 to 2020 were included in this retrospective, single-centre study. Data on reoperation and catheter intervention of hospital survivors were estimated by the Kaplan-Meier method and compared using a long-rank test. Risk factors for reoperation and/or catheter intervention were assessed by multivariate Cox regression analysis.RESULTS: Hospital mortality occurred in 43 patients (8.8%), late death in 12 patients (2.9%) and 43 patients were lost to follow-up. Median follow-up time of 413 hospital survivors was 15.6 (interquartile range 7.0-22.4) years. Reoperations were performed in 83 patients (117 reoperations). Neoaortic valve regurgitation with root dilatation was the second most common indication for reoperation (15/83 patients, 18.1%) after right ventricular outflow tract obstruction (50/83 patients, 60.2%). Risk factors for any reoperation on multivariable analysis were: TGA morphological subtype [TGA with ventricular septal defect: hazard ratio (HR)=1.99, 95% confidence interval (CI) 1.18-3.36; P=0.010 and Taussig-Bing: HR=2.17, 95% CI 1.02-4.64; P=0.045], aortic arch repair associated with ASO (HR=3.03, 95% CI 1.62-5.69; P=0.001) and a non-usual coronary artery anatomy (HR=2.41, 95% CI 1.45-4.00; P=0.001). One hundred and one catheter interventions were performed in 54 patients, usually for relief of supravalvular pulmonary stenosis (44/54 patients, 81.5%) or arch obstruction (10/54 patients, 18.5%). Main risk factor for catheter intervention on multivariable analysis was aortic arch repair associated with ASO (HR=2.95, 95% CI 1.37-6.36; P=0.006). Significant coronary artery stenosis was relatively uncommon (9/413 patients, 2.2%) but may be underrepresented.CONCLUSIONS: Patients after ASO typically have good long-term clinical outcomes but reoperations and interventions remain necessary in some patients. Neoaortic valve regurgitation with root dilatation is the second most common indication for reoperation after right ventricular outflow tract obstruction and an increasing need for neoaortic valve and root redo surgery in future is to be expected. Show less
Bosch, E. van den; Bossers, S.S.M.; Kamphuis, V.P.; Boersma, E.; Roos-Hesselink, J.W.; Breur, J.M.P.J.; ... ; Helbing, W.A. 2021
Background Patients who have undergone the Fontan procedure are at high risk of circulatory failure. In an exploratory analysis we aimed to determine the prognostic value of blood biomarkers in a... Show moreBackground Patients who have undergone the Fontan procedure are at high risk of circulatory failure. In an exploratory analysis we aimed to determine the prognostic value of blood biomarkers in a young cohort who have undergone the Fontan procedure.Methods and ResultsIn multicenter prospective studies patients who have undergone the Fontan procedure underwent blood sampling, cardiopulmonary exercise testing, and stress cardiac magnetic resonance imaging. Several biomarkers including NT-proBNP (N-terminal pro-B-type natriuretic peptide), GDF-15 (growth differentiation factor 15), Gal-3 (galectin-3), ST2 (suppression of tumorigenicity 2), DLK-1 (protein delta homolog 1), FABP-4 (fatty acid-binding protein 4), IGFBP-1 (insulin-like growth factor-binding protein 1), IGFBP-7, MMP-2 (matrix metalloproteinase 2), and vWF (von Willebrand factor) were assessed in blood at 9.6 (7.1-12.1) years after Fontan completion. After this baseline study measurement, follow-up information was collected on the incidence of adverse cardiac events, including cardiac death, out of hospital cardiac arrest, heart transplantation (listing), cardiac reintervention (severe events), hospitalization, and cardioversion/ablation for arrhythmias was collected and the relation with blood biomarkers was assessed by Cox proportional hazard analyses. The correlation between biomarkers and other clinical parameters was evaluated. We included 133 patients who have undergone the Fontan procedure, median age 13.2 (25th, 75th percentile 10.4-15.9) years, median age at Fontan 3.2 (2.5-3.9) years. After a median follow-up of 6.2 (4.9-6.9) years, 36 (27.1%) patients experienced an event of whom 13 (9.8%) had a severe event. NT-proBNP was associated with (all) events during follow-up and remained predictive after correction for age, sex, and dominant ventricle (hazard ratio, 1.89; CI, 1.32-2.68). The severe event-free survival was better in patients with low levels of GDF-15 (P=0.005) and vWF (P=0.008) and high levels of DLK-1 (P=0.041). There was a positive correlation (beta=0.33, P=0.003) between DLK-1 and stress cardiac magnetic resonance imaging functional reserve.ConclusionsNT-proBNP, GDF-15, vWF, DLK-1, ST-2 FABP-4, and IGFBP-7 levels relate to long-term outcome in young patients who have undergone the Fontan procedure. Show less
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... Show moreThe 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. Show less
Ven, J.P.G. van der; Bossers, S.S.M.; Bosch, E. van den; Dam, N.; Kuipers, I.M.; Iperen, G.G. van; ... ; Helbing, W.A. 2021
Objective To assess the atrial and ventricular diastolic function response to dobutamine stress in Fontan patients, and to relate these measurements to exercise capacity and events during the... Show moreObjective To assess the atrial and ventricular diastolic function response to dobutamine stress in Fontan patients, and to relate these measurements to exercise capacity and events during the follow-up.Methods We performed a secondary analysis of a cross-sectional multicentre study of Fontan patients with intra-atrial lateral tunnel (ILT) or extracardiac conduit (ECC) modification. Subjects underwent cardiac MRI during rest and low-dose dobutamine stress, and cardiopulmonary exercise testing. Atrial and diastolic ventricular function parameters were derived from volume-time curves. Medical records were abstracted for a composite endpoint of death, listing for transplant, arrhythmia and reintervention. Spearman's r correlation tests and Cox proportional hazards models were used to assess the relation between the dobutamine response for atrial and diastolic ventricular function and outcomes, including exercise capacity.Results We included 57 patients (26 ECC; 31 ILT) aged 12.8 (IOR (10.3-15.5)) years. During dobutamine stress atrial cyclic volume change increased (3.0 (0.4-5.9) mL/m(2), p<0.001), as did early (1.9 (-1.6 to 3.6) mL/m(2), p=0.001) and late emptying volume (2.2 (0.2-4.4) mL/m(2), p<0.001).Ventricular early filling decreased (-1.6 (-5.7 to 0.7) mL/m(2),p=0.046) and ventricular late filling increased (1.0 (-0.4 to 3.4) mL/m(2),p<0.001) while stroke volume remained similar.Only for patients with the ECC modification, atrial early emptying volume increase correlated with peak oxygen uptake (p=0.66,p=0.002). No other parameter related to exercise capacity.During a median 7.1-year follow-up, 22 patients reached the composite endpoint. No parameter predicted events during the follow-up.Conclusions Dobutamine stress augmented atrial reservoir and pump function for Fontan patients. Atrial early emptying reserve related to exercise capacity in ECC patients. No other atrial or diastolic ventricular function parameter related to outcomes. Show less
Ven, J.P.G. van der; Alsaied, T.; Juggan, S.; Bossers, S.S.M.; Bosch, E. van den; Kapusta, L.; ... ; Helbing, W.A. 2020
Objective: To assess the role of atrial function on exercise capacity and clinical events in Fontan patients.Design: We included 96 Fontan patients from6 tertiary centers, aged 12.8 (IQR 10.1-15.6)... Show moreObjective: To assess the role of atrial function on exercise capacity and clinical events in Fontan patients.Design: We included 96 Fontan patients from6 tertiary centers, aged 12.8 (IQR 10.1-15.6) years, who underwent cardiacmagnetic resonance imaging and cardiopulmonary exercise testing within 12 months of each other from 2004 to 2017. Intra-atrial lateral tunnel (ILT) and extracardiac conduit (ECC) patients were matched 1:1 with regard to age, gender and dominant ventricle. The pulmonary venous atrium was manually segmented in all phases and slices. Atrial function was assessed by volume-time curves. Furthermore, atrial longitudinal and circumferential feature tracking strain was assessed. We determined the relation between atrial function and exercise capacity, assessed by peak oxygen uptake and VE/VCO2 slope, and events (mortality, listing for transplant, re-intervention, arrhythmia) during follow-up.Results: Atrial maximal and minimal volumes did not differ between ILT and ECC patients. ECC patients had higher reservoir function (21.1 [16.4-28.0]% vs 18.2 [10.9-22.2]%, p =.03), lower conduit function and lower total circumferential strain (13.8 +/- 5.1% vs 18.0 +/- 8.7%, p =.01), compared to ILT patients. Only for ECC patients, a better late peak circumferential strain rate predicted better VE/VCO2 slope. No other parameter of atrial function predicted peak oxygen uptake or VE/VCO2 slope. During a median follow-up of 6.2 years, 42 patients reached the composite end-point. No atrial function parameters predicted events during follow-up.Conclusions: ECC patients have higher atrial reservoir function and lower conduit function. Atrial function did not predict exercise capacity or events during follow-up. (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). Show less
Palen, R.L.F. van der; Bom, T. van der; Dekker, A.; Tsonaka, R.; Geloven, N. van; Kuipers, I.M.; ... ; Blom, N.A. 2019
