Nico Blom - Academia.edu (original) (raw)

Papers by Nico Blom

Prenatal Diagnosis, 2020

Objectives: Presumably, changes in fetal circulation contribute to the delay in maturation of the... more Objectives: Presumably, changes in fetal circulation contribute to the delay in maturation of the cortex in fetuses with congenital heart defect (CHD). The aim of the current study is to analyze fetal brain development based on hemodynamic differences, using novel brain-age prediction software. Methods: We have performed detailed neurosonography, including acquiring 3D volumes, prospectively in cases with isolated CHD from 20 weeks onwards. An algorithm that assesses the degree of fetal brain-age automatically was used to compare CHD cases to controls. We stratified CHD cases according to flow and oxygenation profiles by lesion physiology and performed subgroup analyses. Results: A total of 616 ultrasound volumes of 162 CHD cases and 75 controls were analyzed. Significant differences in maturation of the cortex were observed in cases with normal blood flow toward the brain (−3.8 days, 95%CI [−5.5; −2.0], P = <.001) and low (−4.0 days, 95% CI [−6.7; −1.2] P = <.05; hypoplastic left heart syndrome [HLHS]) and mixed (−4.4 days, 95%CI [−6.4; −2.5] p = <.001) oxygen saturation in the ascending aorta (TGA) and in cardiac mixing (eg, Fallot) cases. Conclusion: The current study shows significant delay in brain-age in TGA and Fallot cases as compared to control cases. However, the small differences found in this study questions the clinical relevance.

Prenatal Diagnosis, 2021

Introduction: Neurodevelopmental delay is more common in children born with congenital heart defe... more Introduction: Neurodevelopmental delay is more common in children born with congenital heart defects (CHD), even with optimal perinatal and peri-operative care. It is hypothesized that fetuses with CHD are prone to neurological impairment in utero due to their cardiac defect, possibly leading to delayed cortical development. Methods: Cerebral cortical maturation was assessed with advanced neurosonographic examinations every 4 weeks in fetuses with CHD and compared to control fetuses. Five different primary fissures and four areas were scored (ranging 0-5) by blinded examiners using a cortical maturation scheme. Results: Cortical staging was assessed in 574 ultrasound examinations in 85 CHD fetuses and 61 controls. Small differences in grading were seen in Sylvian and cingulate fissures. (Sylvian fissure: −0.12 grade, 95% CI (−0.23; −0.01) p = 0.05, cingulate fissure: −0.24 grade, 95% CI (−0.38; −0.10) p = <0.001. Other cortical areas showed normal maturation as compared to control fetuses. Conclusion: Small differences were seen in three of the nine analyzed cortical areas in CHD fetuses, in contrast to previous reports on progressive third-trimester delay. The clinical implications of the small differences however, remain unknown. Key points What is already known about this topic? � Neurodevelopmental delay is more prevalent in children with congenital heart defects � Intrauterine hemodynamics are hypothesized to play a role in fetal cerebral abnormalities found in imaging studies What does this study add? � Delays were seen in the Sylvian, cingulate and calcarine fissures by serial neurosonography � The differences we found were stable throughout pregnancy, contradicting previous studies on progressive delay over time This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

International Journal of Neonatal Screening, 2018

Neonatal screening for critical congenital heart defects is proven to be safe, accurate, and cost... more Neonatal screening for critical congenital heart defects is proven to be safe, accurate, and cost-effective. The screening has been implemented in many countries across all continents in the world. However, screening for critical congenital heart defects after home births had not been studied widely yet. The Netherlands is known for its unique perinatal care system with a high rate of home births (18%) and early discharge after an uncomplicated delivery in hospital. We report a feasibility, accuracy, and acceptability study performed in the Dutch perinatal care system. Screening newborns for critical congenital heart defects using pulse oximetry is feasible after home births and early discharge, and acceptable to mothers. The accuracy of the test is comparable to other early-screening settings, with a moderate sensitivity and high specificity.

European Journal of Pediatrics, 2018

Pulse oximetry (PO) screening is used to screen newborns for critical congenital heart defects (C... more Pulse oximetry (PO) screening is used to screen newborns for critical congenital heart defects (CCHD). Analyses performed in hospital settings suggest that PO screening is cost-effective. We assessed the costs and cost-effectiveness of PO screening in the Dutch perinatal care setting, with home births and early postnatal discharge, compared to a situation without PO screening. Data from a prospective accuracy study with 23,959 infants in the Netherlands were combined with a time and motion study and supplemented data. Costs and effects of the situations with and without PO screening were compared for a cohort of 100,000 newborns. Mean screening time per newborn was 4.9 min per measurement and 3.8 min for informing parents. The additional costs of screening were in total €14.71 per screened newborn (€11.00 personnel, €3.71 equipment costs). Total additional costs of screening and referral were €1,670,000 per 100,000 infants. This resulted in an incremental cost-effectiveness ratio of €139,000 per additional newborn with CCHD detected with PO, when compared to a situation without PO screening. A willingness-to-pay threshold of €20,000 per gained QALY for screening in the Netherlands makes the screening likely to be cost-effective. Conclusion: PO screening in the Dutch care setting is likely to be cost-effective. What is Known: • Pulse oximetry is increasingly implemented as a screening tool for critical congenital heart defects in newborns. • Previous studies suggest that the screening in cost-effective and in the USA a reduction in infant mortality from critical congenital heart defects was demonstrated. What is New: • This is the first cost-effectiveness analysis for pulse oximetry screening in a setting with screening after home births, with screening at two moments. • Costs of pulse oximetry screening in a setting with hospital and homebirth deliveries were €14.71 and is likely to be cost-effective accordint to Dutch standards.

JACC: Clinical Electrophysiology, 2018

OBJECTIVES The objective of this study was to evaluate contemporary clinical outcomes and identif... more OBJECTIVES The objective of this study was to evaluate contemporary clinical outcomes and identify triggers for arrhythmias or sudden death in an international cohort of Timothy Syndrome (TS) patients including those with novel TS-associated CACNA1C mutations. BACKGROUND TS is an extremely rare genetic disorder of the L-type cardiac channel Ca v 1.2 encoded by CACNA1C. The syndrome is characterized by multisystem abnormalities consisting of QT prolongation, congenital heart defects, syndactyly, facial dysmorphism, and neurological symptoms.

Heart rhythm, Jan 28, 2018

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an uncommon inherited arrhythmia ... 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...

The Journal of pediatrics, 2018

To assess the accuracy of pulse oximetry screening for critical congenital heart defects (CCHDs) ... 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% ...

European heart journal, Jan 27, 2018

To clarify the clinical characteristics and outcomes of children with SCN5A-mediated disease and ... 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...

European Journal of Pediatrics, 2017

The Netherlands has a unique perinatal healthcare system with a high rate of home births and very... more The Netherlands has a unique perinatal healthcare system with a high rate of home births and very early discharge after delivery in hospital. Although we demonstrated that pulse oximetry (PO) screening for critical congenital heart disease is feasible in the Netherlands, it is unknown whether parents find the screening acceptable when performed in home birth setting. We assessed the acceptability of PO screening to mothers after screening in home setting. A questionnaire was sent electronically to mothers who gave birth and/or had postnatal care under supervision of a community midwife participating in the Pulse Oximetry Leiden Screening (POLS) study, a feasibility study of PO screening in the Dutch care system, performed in the Leiden region, the Netherlands. The questionnaire included questions based on satisfaction, general feelings, and perceptions of PO screening. A total of 1172/1521 (77%) mothers completed the questionnaire. Overall, mothers were happy with the performance of the test (95%), thought their baby was comfortable during the screening (90%) and did not feel stressed while the screening was performed (92%). Most mothers would recommend the test to others (93%) and considered the test important for all babies (93%). Conclusion: Mothers of newborns participating in the study found the PO screening acceptable when performed at home.

Trends in Cardiovascular Medicine, 2017

Age-and gender related differences in QTc-interval are most likely the result of changes in sex-s... more Age-and gender related differences in QTc-interval are most likely the result of changes in sex-specific hormones. Although the exact mechanisms and pathophysiology of sex hormones on the QTc-interval are not known, testosterone appears to shorten the QTc-interval. In females, however, there is a more complex interaction between progesterone and estrogen. In patients with an impaired repolarization, such as Long-QT syndrome (LQTS), the effect of these sex hormones on the QTcinterval is more pronounced with a differing sensitivity between the LQTS genotypes.

Circulation. Arrhythmia and electrophysiology, 2017

In congenital long-QT syndrome, age, sex, and genotype have been associated with cardiac events, ... 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...

Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, Jan 19, 2015

The Journal of Emergency Medicine, 2013

Background Beta-blockers are the mainstay in managing LQTS. Studies comparing the efficacy of com... more Background Beta-blockers are the mainstay in managing LQTS. Studies comparing the efficacy of commonly used betablockers are lacking, and clinicians generally assume they are equally effective. Methods Electrocardiographic and clinical parameters of 382 LQT1/LQT2 patients initiated on propranolol (n ϭ 134), metoprolol (n ϭ 147), and nadolol (n ϭ 101) were analyzed, excluding patients Ͻ1 year of age at beta-blocker initiation. Symptoms before therapy and the first breakthrough cardiac events (BCEs) were documented. Results Patients (56% female, 27% symptomatic, heart rate 76 Ϯ 16 beats/min, QTc 472 Ϯ 46 ms) were started on beta-blocker therapy at a median age of 14 years (interquartile range: 8 to 32 years). The QTc shortening with propranolol was significantly greater than with other beta-blockers in the total cohort and in the subset with QTc Ͼ480 ms. None of the asymptomatic patients had BCEs. Among symptomatic patients (n ϭ 101), 15 had BCEs (all syncopes). The QTc shortening was significantly less pronounced among patients with BCEs. There was a greater risk of BCEs for symptomatic patients initiated on metoprolol compared to users of the other 2 betablockers combined, after adjustment for genotype (odds ratio: 3.95, 95% confidence interval: 1.2 to 13.1, p ϭ 0.025). Kaplan-Meier analysis showed a significantly lower event-free survival for symptomatic patients receiving metoprolol compared to propranolol/nadolol. Conclusions Propranolol has a significantly better QTc shortening effect compared to metoprolol and nadolol, especially in patients with prolonged QTc. Propranolol and nadolol are equally effective, whereas symptomatic patients started on metoprolol are at a significantly higher risk for BCEs. Metoprolol should not be used for symptomatic LQT1 and LQT2 patients.

Foetal supraventricular tachycardia (SVT) with hydrops foetalis is associated with a high morbidi... 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...

Nederlands Tijdschrift voor Geneeskunde, 2005

OBJECTIVE: Analysis of long-term results with radiofrequency catheter ablation (RF ablation) in c... 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

ESC Heart Failure, 2021

Aims We aimed to determine whether in children with dilated cardiomyopathy repeated measurement o... more Aims We aimed to determine whether in children with dilated cardiomyopathy repeated measurement of known risk factors for death or heart transplantation (HTx) during disease progression can identify children at the highest risk for adverse outcome. Methods and results Of 137 children we included in a prospective cohort, 36 (26%) reached the study endpoint (SE: all-cause death or HTx), 15 (11%) died at a median of 0.09 years [inter-quartile range (IQR) 0.03-0.7] after diagnosis, and 21 (15%) underwent HTx at a median of 2.9 years [IQR 0.8-6.1] after diagnosis. Median follow-up was 2.1 years [IQR 0.8-4.3]. Twenty-three children recovered at a median of 0.6 years [IQR 0.5-1.4] after diagnosis, and 78 children had ongoing disease at the end of the study. Children who reached the SE could be distinguished from those who did not, based on the temporal evolution of four risk factors: stunting of length growth (À0.42 vs. À0.02 length Z-score per year, P < 0.001), less decrease in N-terminal pro-B-type natriuretic peptide (NT-proBNP) (À0.26 vs. À1.06 2log pg/mL/year, P < 0.01), no decrease in left ventricular internal diastolic dimension (LVIDd; 0.24 vs. À0.60 Boston Z-score per year, P < 0.01), and increase in New York University Pediatric Heart Failure Index (NYU PHFI; 0.49 vs. À1.16 per year, P < 0.001). When we compared children who reached the SE with those with ongoing disease (leaving out the children who recovered), we found similar results, although the effects were smaller. In univariate analysis, NT-proBNP, length Z-score, LVIDd Z-score, global longitudinal strain (%), NYU PHFI, and age >6 years at presentation (all P < 0.001) were predictive of adverse outcome. In multivariate analysis, NT-proBNP appeared the only independent predictor for adverse outcome, a twofold higher NT-proBNP was associated with a 2.8 times higher risk of the SE (hazard ratio 2.78, 95% confidence interval 1.81-3.94, P < 0.001). Conclusions The evolution over time of NT-proBNP, LVIDd, length growth, and NYU PHFI identified a subgroup of children with dilated cardiomyopathy at high risk for adverse outcome. In this sample, with a limited number of endpoints, NT-proBNP was the strongest independent predictor for adverse outcome.

Pediatric Cardiology, 2019

A single 6-min walk test (6MWT) can be used to identify children with dilated cardiomyopathy (DCM... 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...

Cardiology in the Young, 2019

Aim: In patients after atrioventricular septal defect correction, altered geometry leads to a cha... 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...

International Journal of Cardiology, 2019

Background: Several studies have reported changes in electrocardiographic variables after atrial ... more Background: Several studies have reported changes in electrocardiographic variables after atrial septal defect (ASD) closure. However no temporal electro-and vectorcardiographic changes have been described from acute to long-term follow-up at different ages. We aimed to study electrical remodeling after percutaneous ASD closure in pediatric and adult patients. Methods: ECGs of 69 children and 75 adults (median age 6 [IQR 4-11] years and 45 [IQR 33-54] years, respectively) were retrospectively selected before percutaneous ASD closure and at acute (1-7 days), intermediate (4-14 weeks) and late (6-18 months) follow-up. Apart from electrocardiographic variables, spatial QRS-T angle and ventricular gradient (VG) were derived from mathematically-synthesized vectorcardiograms. Results: In both pediatric and adult patients, the heart rate decreased immediately post-closure, which persisted to late follow-up. The P-wave amplitude also decreased acutely post-closure, but remained unchanged at later follow-up. The PQ duration shortened immediately in children and at intermediate follow-up in adults. The QRS duration and QTc interval decreased at intermediate-term follow-up in both children and adults. In both groups the spatial QRS-T angle decreased at late follow-up. The VG magnitude increased at intermediate follow-up in children and at late follow-up in adults, after an initial decrease in children. Conclusion: In both pediatric and adult ASD patients, electrocardiographic changes mainly occurred directly after ASD closure except for shortening of QRS duration and QTc interval, which occurred at later follow-up. Adults also showed late changes in PQ duration. At 6-to-18 month post-closure, the spatial QRS-T angle decreased, reflecting increased electrocardiographic concordance. The initial acute decrease in VG in children, which was followed by a significant increase, may be the effect of action potential duration dynamics directly after percutaneous ASD closure.