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Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an uncommon inherited arrhythmia disorder characterized by adrenergically-evoked ventricular arrhythmias. Mutations in the cardiac calcium release channel/ryanodine receptor... more
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an uncommon inherited arrhythmia disorder characterized by adrenergically-evoked ventricular arrhythmias. Mutations in the cardiac calcium release channel/ryanodine receptor gene (RYR2) are identified in the majority of patients with CPVT. RyR2 is also the major RyR isoform expressed in the brain. To estimate the prevalence of intellectual disability (ID) and other neurodevelopmental disorders (NDDs) in RYR2-associated CPVT (CPVT1) and to study the characteristics of these patients. We reviewed the medical records of all CPVT1 patients from twelve international centers and analyzed the characteristics of all CPVT1 patients with concomitant NDDs. We functionally characterized the mutations to assess their response to caffeine activation. We did not correct for potential confounders. Among 421 CPVT1 patients, we identified 34 patients with ID (8%; 95% confidence interval, 6-11%). Median age at diagnosis was 9.3 years (int...
Research Interests: Cardiology, Biomedical Engineering, Death, Medicine, Children, and 10 moreInternal Medicine, Ryanodine Receptor, Expression, Arrhythmia, Elsevier, Molecular Identification, Ventricular Tachycardia, Ventricular Arrhythmia, Catecholaminergic polymorphic ventricular tachycardia, and Cardiovascular medicine and haematology
To assess the accuracy of pulse oximetry screening for critical congenital heart defects (CCHDs) in a setting with home births and early discharge after hospital deliveries, by using an adapted protocol fitting the work patterns of... more
To assess the accuracy of pulse oximetry screening for critical congenital heart defects (CCHDs) in a setting with home births and early discharge after hospital deliveries, by using an adapted protocol fitting the work patterns of community midwives. Pre- and postductal oxygen saturations (SpO) were measured ≥1 hour after birth and on day 2 or 3. Screenings were positive if the SpO measurement was <90% or if 2 independent measures of pre- and postductal SpO were <95% and/or the pre-/postductal difference was >3%. Positive screenings were referred for pediatric assessment. Primary outcomes were sensitivity, specificity, and false-positive rate of pulse oximetry screening for CCHD. Secondary outcome was detection of noncardiac illnesses. The prenatal detection rate of CCHDs was 73%. After we excluded these cases and symptomatic CCHDs presenting immediately after birth, 23 959 newborns were screened. Pulse oximetry screening sensitivity in the remaining cohort was 50.0% (95% ...
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To clarify the clinical characteristics and outcomes of children with SCN5A-mediated disease and to improve their risk stratification. A multicentre, international, retrospective cohort study was conducted in 25 tertiary hospitals in 13... more
To clarify the clinical characteristics and outcomes of children with SCN5A-mediated disease and to improve their risk stratification. A multicentre, international, retrospective cohort study was conducted in 25 tertiary hospitals in 13 countries between 1990 and 2015. All patients ≤16 years of age diagnosed with a genetically confirmed SCN5A mutation were included in the analysis. There was no restriction made based on their clinical diagnosis. A total of 442 children {55.7% boys, 40.3% probands, median age: 8.0 [interquartile range (IQR) 9.5] years} from 350 families were included; 67.9% were asymptomatic at diagnosis. Four main phenotypes were identified: isolated progressive cardiac conduction disorders (25.6%), overlap phenotype (15.6%), isolated long QT syndrome type 3 (10.6%), and isolated Brugada syndrome type 1 (1.8%); 44.3% had a negative electrocardiogram phenotype. During a median follow-up of 5.9 (IQR 5.9) years, 272 cardiac events (CEs) occurred in 139 (31.5%) patients...
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Research Interests: Pediatrics, Medicine, Screening, Congenital Heart Defects, Pregnancy, and 15 moreHumans, Questionnaire, Pulse Oximetry, Female, Feasibility Studies, Netherlands, Mothers, Newborn Screening, Acceptability, Oximetry, Postnatal Care, Surveys and Questionnaires, Neonate, Paediatrics and reproductive medicine, and Neonatal screening
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In congenital long-QT syndrome, age, sex, and genotype have been associated with cardiac events, but their effect on the trend in QTc interval has never been established. We, therefore, aimed to assess the effect of age and sex on the QTc... more
In congenital long-QT syndrome, age, sex, and genotype have been associated with cardiac events, but their effect on the trend in QTc interval has never been established. We, therefore, aimed to assess the effect of age and sex on the QTc interval in children and adolescents with type 1 (LQT1) and type 2 (LQT2) long-QT syndrome. QTc intervals of 12-lead resting electrocardiograms were determined, and trends over time were analyzed using a linear mixed-effects model. The study included 278 patients with a median follow-up of 4 years (interquartile range, 1-9) and a median number of 6 (interquartile range, 2-10) electrocardiograms per patient. Both LQT1 and LQT2 male patients showed QTc interval shortening after the onset of puberty. In LQT2 male patients, this was preceded by a progressive QTc interval prolongation. In LQT1, after the age of 12 years, male patients had a significantly shorter QTc interval than female patients. In LQT2, during the first years of life and from 14 to 26...
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Foetal supraventricular tachycardia (SVT) with hydrops foetalis is associated with a high morbidity and mortality rate. If SVT with hydrops foetalis persists despite transplacental therapy, direct foetal treatment can be initiated. One... more
Foetal supraventricular tachycardia (SVT) with hydrops foetalis is associated with a high morbidity and mortality rate. If SVT with hydrops foetalis persists despite transplacental therapy, direct foetal treatment can be initiated. One foetus was found to have SVT with hydrops foetalis during the 29th week of pregnancy, and the condition persisted despite transplacental treatment. Amiodarone was administered directly via the umbilical vein, and the SVT resolved. A second foetus was found to have SVT with hydrops foetalis during the 28th week of pregnancy. The condition persisted despite maternal antiarrhythmic medication. Direct treatment of the foetus with amiodarone was successful. Amiodarone is the treatment of choice for direct foetal therapy for SVT, and can be administered safely via the umbilical vein. Direct foetal therapy should be considered for the treatment of foetal SVT with hydrops foetalis that occurs in the first 31 weeks of pregnancy and persists despite adequate tr...
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OBJECTIVE: Analysis of long-term results with radiofrequency catheter ablation (RF ablation) in children. DESIGN: Retrospective. METHOD: Data were analysed from all 118 paediatric patients or = 10 years of age group in terms of final... more
OBJECTIVE: Analysis of long-term results with radiofrequency catheter ablation (RF ablation) in children. DESIGN: Retrospective. METHOD: Data were analysed from all 118 paediatric patients or = 10 years of age group in terms of final success rate (93% vs. 93%; p = 0.914) and complication rate (3% vs. 7%, p = 0.680). CONCLUSION: The long-term outcome of paediatric patients who underwent RF ablation was good. RF ablation in young children ( <10 years) was found to be safe and effective. These results demonstrate that it is also possible to curatively treat this group of patients with RF ablation in specialized centres
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A single 6-min walk test (6MWT) can be used to identify children with dilated cardiomyopathy (DCM) with a high risk of death or heart transplantation. To determine if repeated 6MWT has added value in addition to a single 6MWT in... more
A single 6-min walk test (6MWT) can be used to identify children with dilated cardiomyopathy (DCM) with a high risk of death or heart transplantation. To determine if repeated 6MWT has added value in addition to a single 6MWT in predicting death or heart transplantation in children with DCM. Prospective multicenter cohort study including ambulatory DCM patients ≥ 6 years. A 6MWT was performed 1 to 4 times per year. The distance walked was expressed as percentage of predicted (6MWD%). We compared the temporal evolution of 6MWD% in patients with and without the study endpoint (SE: all-cause death or heart transplantation), using a linear mixed effects model. In 57 patients, we obtained a median of 4 (IQR 2–6) 6MWTs per patient during a median of 3.0 years of observation (IQR 1.5–5.1). Fourteen patients reached a SE (3 deaths, 11 heart transplantations). At any time during follow-up, the average estimate of 6MWD% was significantly lower in patients with a SE compared to patients withou...
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Aim: In patients after atrioventricular septal defect correction, altered geometry leads to a changed position and subsequent flow over the left ventricular outflow tract. We hypothesised that this altered flow may influence haemodynamics... more
Aim: In patients after atrioventricular septal defect correction, altered geometry leads to a changed position and subsequent flow over the left ventricular outflow tract. We hypothesised that this altered flow may influence haemodynamics in the ascending aorta. Methods: In total, 30 patients after atrioventricular septal defect correction (age 27.6 ± 12.8 years) and 28 healthy volunteers (age 24.8 ± 13.7 years) underwent 4D flow cardiovascular magnetic resonance. Left ventricular ejection fraction and mean and peak wall shear stress calculated at ascending aortic peak systole were obtained from cardiovascular magnetic resonance. Left ventricular outflow tract data including velocity and diameter were obtained from echocardiography. Results: Patients showed a higher mean (911 ± 173 versus 703 ± 154 mPa, p = 0.001) and peak ascending aortic wall shear stress (1264 ± 302 versus 1009 ± 240 mPa, p = 0.001) compared to healthy volunteers. Increased blood flow velocities over the left ven...
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Visualization and quantification of the adverse effects of distorted blood flow are important emerging fields in cardiology. Abnormal blood flow patterns can be seen in various cardiovascular diseases and are associated with increased... more
Visualization and quantification of the adverse effects of distorted blood flow are important emerging fields in cardiology. Abnormal blood flow patterns can be seen in various cardiovascular diseases and are associated with increased energy loss. These adverse energetics can be measured and quantified using 3-dimensional blood flow data, derived from computational fluid dynamics and 4-dimensional flow magnetic resonance imaging, and provide new, promising hemodynamic markers. In patients with palliated single-ventricular heart defects, the Fontan circulation passively directs systemic venous return to the pulmonary circulation in the absence of a functional subpulmonary ventricle. Therefore, the Fontan circulation is highly dependent on favorable flow and energetics, and minimal energy loss is of great importance. A focus on reducing energy loss led to the introduction of the total cavopulmonary connection (TCPC) as an alternative to the classical Fontan connection. Subsequently, m...
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Survival after surgical repair of a ventricular septal defect (VSD) is good, but, as in almost all congenital heart diseases, late complications are frequent in adulthood. The exact mechanisms, timing and who is at risk are not fully... more
Survival after surgical repair of a ventricular septal defect (VSD) is good, but, as in almost all congenital heart diseases, late complications are frequent in adulthood. The exact mechanisms, timing and who is at risk are not fully understood. Altered cardiac autonomic nervous system (ANS) activity might play a role in these long-term sequelae. The aim of this study was to extensively evaluate children late after VSD repair including their cardiac ANS activity, cardiac function and exercise capacity. Thirty-three patients after surgical VSD repair and 66 healthy age-matched controls underwent 24-h monitoring of ANS control and cardiac output using impedance cardiography, detailed echocardiography and cardiopulmonary exercise testing. Ambulatory cardiac ANS control was not different between the patients and the controls. Right ventricular function, exercise capacity and ambulatory cardiac output were decreased in patients compared with the controls. No relationships were found betw...
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The aim of the current study was to assess the scan-rescan reproducibility of left ventricular (LV) kinetic energy (KE), viscous energy loss (EL) and vorticity during diastole from four-dimensional flow magnetic resonance imaging (4D flow... more
The aim of the current study was to assess the scan-rescan reproducibility of left ventricular (LV) kinetic energy (KE), viscous energy loss (EL) and vorticity during diastole from four-dimensional flow magnetic resonance imaging (4D flow MRI) in healthy subjects. Twelve volunteers (age 27 ± 3 years) underwent whole-heart 4D flow MRI twice in one session. In-scan consistency was evaluated by correlation between KE and EL. ELwas computed to measure the amount of EL relative to KE over diastole. Scan-rescan analysis was performed to test reproducibility of volumetric measurements of KE, EL, ELand vorticity in the LV over early (E) and late (A) diastolic filling. In-scan consistency between KE and EL was strong-excellent (E-filling scan1: r = 0.92, P < 0.001; scan2: ρ = 0.96, P < 0.001 and A-filling scan1: ρ = 0.87, P < 0.001; scan2: r = 0.99, P < 0.001). For the majority of subjects (10 out of 12), KE and EL measures showed good to strong reproducibility. However, with a w...
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Normal values of the mathematically-synthesized vectorcardiogram (VCG) are lacking for children. Therefore, the objective of this study was to assess normal values of the pediatric synthesized VCG (spatial QRS-T angle [SA] and ventricular... more
Normal values of the mathematically-synthesized vectorcardiogram (VCG) are lacking for children. Therefore, the objective of this study was to assess normal values of the pediatric synthesized VCG (spatial QRS-T angle [SA] and ventricular gradient [VG]). Electrocardiograms (ECGs) of 1263 subjects (0-24 years) with a normal heart were retrospectively selected. VCGs were synthesized by the Kors matrix. Normal values (presented as 2nd and 98th percentiles) were assessed by quantile regression with smoothing by splines. Our results show that heart rate decreased over age, QRS duration increased and QTc interval remained constant. The SA initially decreased and increased again from the age of 8 years. The VG magnitude was relatively stable until the age of 2 years, after which it increased. Normal values of the pediatric ECG and VCG (VG and SA) were established. These normal values could be important for future studies using VG and SA for risk stratification in heart disease in children.
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Atrioventricular septal defect (AVSD) has an incidence of 4-5.3 per 10.000 live births and is associated with Down syndrome (DS). Data on arrhythmias and sudden cardiac death (SCD) after AVSD correction is scarce. To analyse the incidence... more
Atrioventricular septal defect (AVSD) has an incidence of 4-5.3 per 10.000 live births and is associated with Down syndrome (DS). Data on arrhythmias and sudden cardiac death (SCD) after AVSD correction is scarce. To analyse the incidence of post-operative arrhythmias and SCD after AVSD correction and explore risk factors. This is a retrospective multicenter study including patients after biventricular AVSD correction. Univariate and multivariate analyses were performed to explore risk factors. A total of 415 patients were included with a mean follow-up duration of 9years (range; <30days-47years). Early post-operative SVTs were documented in 33 patients (8%) and late post-operative SVTs in 15 patients (3.6%). Non-syndromic AVSD (p=0.022, HR=2.64; 95% CI=1.15-6.04) and cAVSD (p=0.005, HR=3.7; 95% CI=1.39-7.51) were independent risk factors for early post-operative SVTs and significant more late post-operative SVTs occurred in non-syndromic patients (p=0.016, HR=6.38; 95% CI=1.42-2...
Research Interests: Cardiology, Incidence Geometry, Adolescent, Medicine, Down Syndrome, and 15 moreHumans, Child, Internal Medicine, Female, Male, Incidence, Risk factors, Middle Aged, Adult, Retrospective Studies, Sudden Cardiac Death, Risk Factors, Postoperative Complications, Child preschool, and Cardiovascular medicine and haematology
Research Interests: Cardiology, Medicine, Cardiac Surgery, Echocardiography, Heart Failure, and 15 moreHumans, Internal Medicine, Female, Male, Medical Physiology, Tissue Doppler Imaging, Retrospective Studies, Congenital Heart Disease, Heart Ventricles, Postoperative care, Cardiopulmonary bypass, Child preschool, Diastole, Cardiovascular medicine and haematology, and Ventricular Function
Research Interests: Magnetic Resonance Imaging, Medicine, Humans, Disease, Velocity, and 15 moreCardiac Imaging, Cardiovascular Imaging, Blood Flow, Prognosis, Three Dimensional Flow, Reproducibility of Results, Coronary Circulation, Myocardial Perfusion Imaging, Blood Flow Velocity, Cardiovascular Magnetic Resonance, Predictive value of tests, Heart Diseases, Severity of Illness Index, Cardiovascular medicine and haematology, and Coronary Vessels
To assess ductus arteriosus (DA) blood flow directly after birth in healthy term infants after elective caesarean section. In healthy term newborns, echocardiography was performed at 2, 5 and 10 min after birth to monitor cardiac output... more
To assess ductus arteriosus (DA) blood flow directly after birth in healthy term infants after elective caesarean section. In healthy term newborns, echocardiography was performed at 2, 5 and 10 min after birth to monitor cardiac output and DA blood flow. Heart rate (HR) was assessed using ECG. The delivery rooms of the Leiden University Medical Center. 24 healthy term infants born after a caesarean section were included in this study. Mean (SD) HR did not change (158 (18) beats per minute (bpm), 5 min (159 (23) bpm) and 10 min (156 (19) bpm). DA diameter decreased from 5.2 (1.3) mm at 2 min to 4.6 (1.3) mm at 5 min (p=0.01) to (3.9 (1.2) mm) (p=0.01) at 10 min. Right-to-left DA shunting was unaltered (median (IQR) 95 (64-154) mL/kg/min to 90 (56-168) mL/kg/min and 80 (64-120) mL/kg/min, respectively (ns)), whereas left-to-right shunting significantly increased between 2 and 5 min (41 (31-70) mL/kg/min vs 67 (37-102) mL/kg/min (p=0.01)) and increased significantly between 2 and 10 m...
Research Interests: Radiology, Medicine, Caesarean Section, Pregnancy, Humans, and 13 moreHemodynamics, Female, Heart rate, Newborn Infant, Cardiac Output Monitoring, Blood Flow, Cesarean Section, Ductus Arteriosus, Perinatal Care, Postoperative care, Pulmonary Artery, Cardiac output, and Paediatrics and reproductive medicine
Background: During neonatal transition, ductus arteriosus (DA) flow changes from right-to-left to left-to-right and contributes considerably to the increase in pulmonary blood flow. Large transpulmonary pressures generated by crying at... more
Background: During neonatal transition, ductus arteriosus (DA) flow changes from right-to-left to left-to-right and contributes considerably to the increase in pulmonary blood flow. Large transpulmonary pressures generated by crying at birth can influence the DA shunt. Objective: This study aimed to assess differences in DA shunt during quiet breathing and crying directly after birth. Methods: In healthy term infants born by caesarean section, echocardiography was performed at 2, 5 and 10 min after birth. The velocity time integral of DA flow, DA flow ratio (right-to-left/left-to-right flow) and left ventricular output were assessed using echocardiography. Shunting was compared within each patient during crying and quiet breathing, and between time points. Results: A total of 23 infants were studied. The velocity time integral of left-to-right shunting was significantly larger during the inspiratory phase of crying than during quiet breathing [12.8 (9.2-17.4) vs. 5.9 (3.9-7.7) cm at...
Research Interests: Cardiology, Neonatology, Medicine, Echocardiography, Pregnancy, and 15 moreHumans, Internal Medicine, Hemodynamics, Female, Male, Clinical Sciences, Newborn Infant, Crying, Cesarean Section, Parturition, Breathing, Ductus Arteriosus, Heart Ventricles, Blood Flow Velocity, and Paediatrics and reproductive medicine
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Research Interests: Quality of life, Adolescent, Medicine, Pediatric Cardiology, Anxiety, and 15 moreHumans, Child, Female, Male, Checklist, Young Adult, Cardiac Arrhythmias, Questionnaires, Time Factors, ANXIETY, Implantable defibrillators-cardioverters, Child preschool, Psychological functioning, Cardiovascular medicine and haematology, and pediatric patients
Research Interests: Cardiology, Biomedical Engineering, Medicine, Heart Failure, Congenital Heart Defects, and 13 moreHumans, Internal Medicine, Hemodynamics, Female, Left Ventricular Dysfunction, Clinical Sciences, Newborn Infant, Congenital Heart Surgery, Left Ventricular Function, Heart Block, cardiac resynchronization therapy, Ventricular Function, and ventricle
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Research Interests: Cardiology, Biomedical Engineering, Medicine, Humans, Child, and 13 moreInternal Medicine, Mutation, Female, Male, Siblings, Long QT syndrome, Recurrence, Implantable defibrillators-cardioverters, Ventricular Arrhythmia, Periodic Paralysis, Torsades de pointes, Child preschool, and Cardiovascular medicine and haematology
A premature neonate with hydrops was born at 32 weeks of gestation after successful direct fetal amiodarone therapy via cordocentesis for incessant supraventricular tachycardia. After birth the tachycardia could not be controlled despite... more
A premature neonate with hydrops was born at 32 weeks of gestation after successful direct fetal amiodarone therapy via cordocentesis for incessant supraventricular tachycardia. After birth the tachycardia could not be controlled despite high doses of amiodarone and flecainide and the patient developed severe respiratory and circulatory failure. After 3 weeks, weighing 2 kg, he underwent successful and uncomplicated catheter ablation of a left free-wall accessory pathway using low-energy radiofrequency. radiofrequency catheter ablation is rarely used in neonates, but when used with caution may provide the optimal treatment.
Research Interests: Pediatrics, Medicine, Electrocardiography, Echocardiography, Humans, and 15 moreShock, Male, Low Energy Buildngs, Radiofrequency Ablation, Newborn Infant, Public health systems and services research, Radiofrequency, Catheter ablation, Hydrops Fetalis, Amiodarone, supraventricular tachycardia, accessory pathway, Respiratory insufficiency, Paediatrics and reproductive medicine, and Infant Premature
Research Interests: Medicine, Cardiac Surgery, Congenital Heart Defects, Humans, Child, and 15 moreInfant, Newborn Infant, European, Hybrid Approach, Medicine and Health Sciences, Anastomosis, Hypoplastic Left Heart Syndrome, Aortic arch, Pulmonary Artery, Right Ventricular Outflow Tract, Intraoperative Period, Reoperation, Child preschool, Arterial Occlusive Diseases, and Cardiovascular medicine and haematology
Background— The developmental mechanisms underlying the persistence of myocardial accessory atrioventricular pathways (APs) that bypass the annulus fibrosis are mainly unknown. In the present study, we investigated the role of... more
Background— The developmental mechanisms underlying the persistence of myocardial accessory atrioventricular pathways (APs) that bypass the annulus fibrosis are mainly unknown. In the present study, we investigated the role of epicardium-derived cells (EPDCs) in annulus fibrosis formation and the occurrence of APs. Methods and Results— EPDC migration was mechanically inhibited by in ovo microsurgery in quail embryos. In ovo ECGs were recorded in wild-type (n=12) and EPDC-inhibited (n=12) hearts at Hamburger-Hamilton (HH) stages 38 to 42. Subsequently, in these EPDC-inhibited hearts (n=12) and in additional wild-type hearts (n=45; HH 38–42), ex ovo extracellular electrograms were recorded. Electrophysiological data were correlated with differentiation markers for cardiomyocytes (MLC2a) and fibroblasts (periostin). In ovo ECGs showed significantly shorter PR intervals in EPDC-inhibited hearts (45±10 ms) than in wild-type hearts (55±8 ms, 95% CI 50 to 60 ms, P =0.030), whereas the QRS ...
Research Interests: Biology, Medicine, Electrocardiography, Animals, Fibrosis, and 13 moreClinical Sciences, Embryonic Development, Public health systems and services research, Circulation, Arrhythmia, Pericardium, Quail, Human Fibroblasts, Embryos, Periostin, fibroblasts, accessory pathway, and Cardiovascular medicine and haematology
Background— Fetal and neonatal atrioventricular (AV) reentrant tachycardias can be life-threatening but resolve in most cases during the first year of life. The transient presence of accessory AV myocardial connections during annulus... more
Background— Fetal and neonatal atrioventricular (AV) reentrant tachycardias can be life-threatening but resolve in most cases during the first year of life. The transient presence of accessory AV myocardial connections during annulus fibrosus development may explain this phenomenon. Methods and Results— A total of 45 human embryonic, fetal, and neonatal sectioned hearts (4 to 36 weeks of development) were studied immunohistochemically. Accessory myocardial AV connections were quantified and categorized according to their specific location, and 3D reconstructions were made. Between 4 and 6 weeks of development, the atrial and ventricular myocardium was continuous at the primitive AV canal. At 6 to 10 weeks, numerous accessory myocardial AV connections were identified in the left (45%), right (35%), and septal (20%) regions of the AV junction. Most right-sided accessory connections comprised distinct myocardial strands, whereas left-sided connections consisted of larger myocardial con...
Research Interests: Embryology, Immunohistochemistry, Medicine, Anatomy, Humans, and 12 moreThree Dimensional Imaging, Heart, 3-D Reconstruction, Clinical Sciences, Newborn Infant, Public health systems and services research, First Year, Circulation, Arrhythmia, Fetus, atrioventricular node, and Cardiovascular medicine and haematology
A newborn girl with progressive respiratory distress and cyanosis was found to have severely obstructed supracardiac total pulmonary venous return (TAPVR). Stenting of the stenosis provided immediate and effective relief of the... more
A newborn girl with progressive respiratory distress and cyanosis was found to have severely obstructed supracardiac total pulmonary venous return (TAPVR). Stenting of the stenosis provided immediate and effective relief of the obstruction until corrective surgery was performed. Catheter intervention should be considered in high-risk infants with obstructed supracardiac TAPVR as part of the strategy for preoperative cardiovascular stabilization.
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Research Interests: Cardiology, Magnetic Resonance Imaging, Adolescent, Medicine, Congenital Heart Defects, and 15 moreHumans, Child, Internal Medicine, Mass, Hemodynamics, Female, Male, Cardiac Catheterization, Adult, Congenital Heart Disease, Ejection Fraction, Cardiac Magnetic Resonance Imaging, Heart Valve Prosthesis Implantation, Diastole, and Cardiovascular medicine and haematology
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Arrhythmias in congenital heart disease: a position paper of the European Heart Rhythm Association (EHRA), Association for European Paediatric and Congenital Cardiology (AEPC), and the European Society of Cardiology (ESC) Working Group on Grown-up Congenital heart disease, endorsed by HRS, PACES,...more
The population of patients with congenital heart disease (CHD) is continuously increasing with more and more patients reaching adulthood. A significant portion of these young adults will suffer from arrhythmias due to the underlying... more
The population of patients with congenital heart disease (CHD) is continuously increasing with more and more patients reaching adulthood. A significant portion of these young adults will suffer from arrhythmias due to the underlying congenital heart defect itself or as a sequela of interventional or surgical treatment. The medical community will encounter an increasing challenge as even most of the individuals with complex congenital heart defects nowadays become young adults. Within the past 20 years, management of patients with arrhythmias has gained remarkable progress including pharmacological treatment, catheter ablation, and device therapy. Catheter ablation in patients with CHD has paralleled the advances of this technology in pediatric and adult patients with structurally normal hearts. Growing experience and introduction of new techniques like the 3D mapping systems into clinical practice have been particularly beneficial for this growing population of patients with abnorma...
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GNB5 encodes the G protein β subunit 5 and is involved in inhibitory G protein signaling. Here, we report mutations in GNB5 that are associated with heart-rate disturbance, eye disease, intellectual disability, gastric problems,... more
GNB5 encodes the G protein β subunit 5 and is involved in inhibitory G protein signaling. Here, we report mutations in GNB5 that are associated with heart-rate disturbance, eye disease, intellectual disability, gastric problems, hypotonia, and seizures in nine individuals from six families. We observed an association between the nature of the variants and clinical severity; individuals with loss-of-function alleles had more severe symptoms, including substantial developmental delay, speech defects, severe hypotonia, pathological gastro-esophageal reflux, retinal disease, and sinus-node dysfunction, whereas related heterozygotes harboring missense variants presented with a clinically milder phenotype. Zebrafish gnb5 knockouts recapitulated the phenotypic spectrum of affected individuals, including cardiac, neurological, and ophthalmological abnormalities, supporting a direct role of GNB5 in the control of heart rate, hypotonia, and vision.
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The majority of ventricular tachycardias (VTs) in repaired tetralogy of Fallot (rTOF) are related to anatomically defined isthmuses. We aimed to identify specific electroanatomical characteristics of anatomical isthmuses (AI) related to... more
The majority of ventricular tachycardias (VTs) in repaired tetralogy of Fallot (rTOF) are related to anatomically defined isthmuses. We aimed to identify specific electroanatomical characteristics of anatomical isthmuses (AI) related to VT which may allow for individualized risk stratification and tailored ablation. Seventy-four consecutive rTOF patients (40 ± 16 years, 63% male) underwent VT induction and right ventricular electroanatomical voltage and activation mapping during sinus rhythm (SR) to identify the presence and characteristics of AI (isthmus width, length and conduction velocity index [CVi]). Twenty-eight patients were inducible for 41 VTs. All 74 patients had at least one AI. However, AI in patients with VT were longer (22 ± 7 vs. 16 ± 7 mm, P = 0.001), narrower (20 ± 8 vs. 28 ± 11 mm, P < 0.001) and had lower CVi (0.36 ± 0.34 vs. 0.78 ± 0.24 m/s, P < 0.001). Thirty-seven VTs in 24 patients were mapped (pace-, entrainment mapping, and/or VT termination by ablati...
During cardiac development the heart tube loops and is septated into a four-chambered structure. The initial peristaltic contraction of the primitive myocardium is replaced by a system of working myocardium and a myocardial-derived... more
During cardiac development the heart tube loops and is septated into a four-chambered structure. The initial peristaltic contraction of the primitive myocardium is replaced by a system of working myocardium and a myocardial-derived central and peripheral conduction system. The genes guiding this differentiation process are still under investigation and it has yet to be decided whether we are dealing with a recruitment or a specification model. We have shown that the complicated looping process of the heart tube brings together the essential parts of the sinoatrial and primary ring myocardium, that are the embryonic precursors of the definitive conduction system. From our studies it is evident that during development there are sinoatrial tracts that run between the sinoatrial and the atrioventricular node as well as tracts surrounding the pulmonary veins and the coronary sinus. Furthermore, we show that both in the chicken and mouse embryo neural crest cells reach the confinement of the central conduction system through the inflow and outflow tract. For the Purkinje system there is a close approximation with the epicardium-derived cells. We postulate that both extracardiac-derived cell types have an influence on the differentiation of the definitive conduction system.
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Major coronary artery anomalies are extremely rare in childhood. We wanted to assess the historical and diagnostic features and the therapeutic options of three distinct types of coronary artery anomalies: abnormal origin of the left... more
Major coronary artery anomalies are extremely rare in childhood. We wanted to assess the historical and diagnostic features and the therapeutic options of three distinct types of coronary artery anomalies: abnormal origin of the left coronary artery from the pulmonary artery (ALCAPA), coronary fistula and coronary stenosis. In a retrospective study, 33 children with these types of coronary artery disease were identified, 15 with ALCAPA, 12 with fistula and six with coronary stenosis. History, physical examination, ECG, X-ray, echocardiography, angiography, therapy and outcome were reviewed. ALCAPA showed distinct typical echocardiographic characteristics. Coronary artery fistula could be identified by a typical murmur and echocardiographic evidence of coronary dilatations. Coronary stenosis should be suspected by the clinical picture in a specific context. rare coronary artery anomalies can be accurately diagnosed in childhood. Timely therapy yields good prognosis.